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22099407
[Prenatal diagnosis and management of foetal lung lesions].
Foetal lung lesions are mon (<1/1000 deliveries). Prenatal ultrasound can distinguish echogenic and cystic lesions.
22099406
[New antithrombotic drugs for the treatment of venous thromboembolism].
Numerous newer anticoagulants are under advanced clinical development for the treatment of venous thromboembolism. These new drugs specifically inhibit activated factors II or X, with predictable effects and no need for dose modification and laboratory monitoring. The main direct activated factor X (FXa) inhibitors are rivaroxaban, apixaban and edoxaban. They are taken orally once or twice per day. Dabigatran is the main inhibitor of activated factor II (IIa) and is administered orally once daily. Dabigatran and rivaroxaban are already licensed for the prevention of thromboembolic events following major orthopedic surgery such as total hip and knee replacement. They will probably soon be authorized for the treatment of venous thromboembolism, if they both confirm their efficacy and safety, and can demonstrate their cost-effectiveness. However, only rivaroxaban has been tested as a stand-alone treatment, whereas dabigatran pared to vitamin K antagonism after a standard treatment regimen based on heparin or its derivates.
22099408
[Multidrug resistant tuberculosis -- its extent, hazard and possible solutions].
Multidrug resistant tuberculosis (MDR-TB) has spread to most regions of the world and represents a serious threat to the success of the struggle against tuberculosis. It can result from errors in management that favour the selection of drug resistant organisms and can in the worst case lead to the development of extremely resistant organisms (XDR-TB) which are practically untreatable. The current strategies bating this problem are, on the one hand, the rapid identification and tracking of resistant strains using molecular genetic techniques and, on the other hand, careful drug management in individual cases using second line agents. At the level of public health, the most important measures are those which prevent or correct the processes which can drive the creation of new cases of MDR-TB. This can have implications for the modification and development of national strategies. The future of the fight against tuberculosis depends in part on the success of strategies bat the development and spread of MDR-TB.
22099409
[Bacteriological tests for tuberculosis].
This review describes current developments for the bacteriological diagnosis of active tuberculosis. It deals mainly with molecular methods, describing their performance and how they can be integrated into more traditional diagnostic approaches. At present, microscopic examination and culture are still essential for the diagnosis of TB and to guide therapeutic decisions. Nucleic acid amplification and line probe assays speed up the identification and susceptibility testing of mycobacteria in AFB smear positive specimens or in culture. They are also efficient parison of M. tuberculosis strains with each other (genotyping). On the other hand, at present, molecular tests are not applicable for diagnosis in smear negative specimens and even less so for diagnosis of culture-negative tuberculosis. The use of serology for antibody/antigen detection is not useful and it is not appropriate to assays based on the release of interferon-γ release as they are currently available. Notable progress has been made but more sensitive diagnostic tests for TB are still urgently needed.
22099410
[Epidemiological novelties in lung cancer].
Lung cancer is the mon cause of cancer-related mortality throughout the world representing around 18% of the total. There is still a male predominance but this is ing less pronounced and in the US, lung cancer is now the mon cause of cancer-related mortality in women. In France, it had risen to second place in women in 2005 after having been in 6th place in 1975. Median age at diagnosis differs according to countries and health system and is around 70 years in the US and around 65 years in France. The distribution of histological subtypes has changed considerably during recent decades with an increasing frequency of adenocarcinoma at the expense of squamous cell carcinoma. The main risk factor for lung cancer remains active tobacco smoking but the attributable risk of smoking varies from one country to another and according to gender. In Japan, the great majority of lung cancer in women is not attributable to active tobacco smoking. Environmental tobacco smoke exposure has a less important role than active tobacco smoking although it is not negligible. The specific impact of smoking cannabis is difficult to assess precisely as, in most cases, it is mixed with tobacco. However, despite important differences with tobacco smoke, cannabis exposure doubles the risk of developing lung cancer. Occupational risk factors have for a long time been neglected and thus occupational lung cancers have been under-reported. Finally, lung cancer in never-smokers is driving considerable interest as it represents by itself the 7th largest cause of mortality due to cancer. Risk factors involved might be air pollution (indoors and outdoors) but also hormone replacement therapy in women.
22099411
[Exacerbations of asthma--precipitating factors: drugs].
Asthmatic exacerbations are sometimes triggered by medications, primarily the non-steroidal anti-inflammatory agents (NSAIDS) and beta-blockers. Asthma attacks induced by NSAIDS occur rapidly and can be severe. Widal syndrome is a specific disease entity whose physiopathology remains pletely explained. Asthma is characteristically severe and steroid dependent; desensitisation with aspirin has been proposed, but this remains controversial. Beta-blockers are contra-indicated in asthma; the β1 "cardioselectivity" of some agents is not absolute, disappearing at high doses and the "partial agonists" are not better tolerated. However, certain authors have called into question the harmful effect of beta-blockade in moderate and stable asthma. More studies are needed, but the current data suggest that in some cases beta-blockers may be safe but their use requires close supervision. Other molecules can pose problems in asthmatics (dipyridamole, synthetic sex hormones and certain excipients). On the whole, there has been little innovation concerning the hazard that drugs can pose for some asthmatics. The task for the future will be to specify the physiopathology of Widal syndrome, and to clarify the categories of patients in whom beta-blockers can be safely employed as the public health consequences of cardiovascular pathologies make this an important issue for lung specialists.
22099412
[Symptoms and natural history of COPD: role of the distal airways].
Symptoms and natural history of COPD: role of the distal airways. The natural history of chronic obstructive pulmonary disease (COPD) is characterized by a progressive worsening of airway obstruction and health-related quality of life, and an increased risk of death. Symptoms of COPD are dominated by cough, sputum production and dyspnoea whose intensity varies between individuals and during the progression of the disease. The symptoms and natural history of COPD result from damage to the airways, including remodelling and inflammation, mence and are predominant in the distal airways (DA). This article examines the relationship between symptoms and the natural history of COPD in the light of large cohorts published in the literature. The role of the DA in the development and intensity of symptoms and in the natural history of COPD is difficult to define. We have attempted to examine this role using either published studies which have evaluated the relationship between lung structure and the clinical phenotypes of COPD or studies involving the earlier stages of the disease when damage to the DA are known to be predominant. These data suggest a potential role for early therapies targeting remodelling and inflammation in the distal airways of patients suffering from COPD.
22099415
Bronchoscopic treatments for emphysema.
In late stage chronic obstructive pulmonary disease, emphysema can worsen respiratory symptoms, not only via the loss of surface for gas exchange, but also via alterations in mechanical properties of the respiratory system (dynamic and static hyperinflation). Emphysematous lung volume reduction aims at improving respiratory mechanics and symptomatology in patients with advanced emphysema. Lung volume reduction surgery (LVRS) has been shown to be effective in selected patient populations, but its morbidity and costs are quite elevated. Alternatives to LVRS do not remove emphysematous lung tissue per se, but rather consist of devices aiming to: 1) reduce the volume that affected lung parenchyma occupies (unidirectional endobronchial valves or plugs, parenchymal injection of bioactive scarring agents); 2) redistribute ventilatory flow (airway bypass systems). Preliminary studies of these devices have shown that they are relatively safe. These also show modest benefits in exercise capacity, although individual subjects can experience spectacular improvement. Current objective is to identify predictors of response to therapy with such devices.
22099416
Respiratory effects of manufactured nanoparticles.
Nanotechnology is the set of techniques used to engineer, characterize, and produce materials that have at least one dimension within the nanoscale. These nanomaterials, or nanoobjects, include nanoparticles and nanotubes. As dictated by the laws of quantum physics, a size within the nanoscale results in unique physicochemical properties and distinctive behaviors. Nanotechnology has a host of applications in fields ranging from cosmetology to the industry and medicine. The production and use of nanomaterials are expanding at a brisk pace. However, concerns are emerging about the potential health effects of nanoparticles in the short and long terms. These concerns are rooted in data on the harmful health effects of micrometric airborne particulate matter. Conceivably, these adverse effects might be amplified when the particles are within the nanoscale. This article is a nonexhaustive overview of current data on the penetration, deposition, translocation, and elimination of inhaled nanoparticles and on the respiratory effects of metallic nanoparticles (with special attention to titanium dioxide) and carbon nanotubes. Both in vivo and in vitro studies consistently found biological effects of nanoparticles on the respiratory system, including oxidative stress generation, proinflammatory and prothrombotic effects, pulmonary fibrosis and emphysema, and DNA damage. Improved knowledge of the potential biological effects of nanoparticles is needed to guide preventive strategies for the workplace and/or general population if needed.
22099417
Swallowing disorders, pneumonia and respiratory tract infectious disease in the elderly.
Swallowing disorders (or dysphagia) mon in the elderly and their prevalence is often underestimated. They may result in plications including dehydration, malnutrition, airway obstruction, aspiration pneumonia (infectious process) or pneumonitis (chemical injury caused by the inhalation of sterile gastric contents). Moreover the repercussions of dysphagia are not only physical but also emotional and social, leading to depression, altered quality of life, and social isolation. While some changes in swallowing may be a natural result of aging, dysphagia in the elderly is mainly due to central nervous system diseases such as stroke, parkinsonism, dementia, medications, local oral and oesophageal factors. To be effective, management requires a multidisciplinary team approach and a careful assessment of the patient's oropharyngeal anatomy and physiology, medical and nutritional status, cognition, language and behaviour. Clinical evaluation can pleted by a videofluoroscopic study which enables observation of bolus movement and movements of the oral cavity, pharynx and larynx throughout the swallow. The treatment depends on the underlying cause, extent of dysphagia and prognosis. Various categories of treatment are available, pensatory strategies (postural changes and dietary modification), direct or indirect therapy techniques (swallow manoeuvres, medication and surgical procedures).
22099418
Endothelin receptor antagonists -- their role in pulmonary medicine.
Understanding of the function of endothelin-1 in the pathophysiology of endothelial disease, in particular pulmonary arterial hypertension (PAH), has paved the way for the development of endothelin-receptor antagonists (ERAs) and explains the leading role they now play in the treatment armamentarium for this disease.
22099419
Snapshot of Quantiferon TB gold testing in Northern Mexico.
Most people infected with Mycobacterium tuberculosis have an asymptomatic condition named latent tuberculosis. These people do not have bacilli in the corporal secretions and are hard to diagnose by conventional laboratory tests. Diagnosis of latent tuberculosis infection (LTBI) in México is based on the tuberculin skin test (TST). This test has disadvantages, principally because the vaccine containing the Bacille Calmette-Guérin (BCG) is applied to 99% of this population and causes false positive TST es. Recently, interferon-gamma release assays (IGRA) have been demonstrated to be a good test to detect latent tuberculosis with equal or better sensitivity to TST and without interference from BCG. However, in México the IGRA are an mon test due to the higher pared to TST. The main objective of this work was demonstrate the potential utility of the Quantiferon TB(®) gold in tube (QTB(®)-GIT) test to detect latent TB in a population from northern México. Samples from 106 subjects with close contact, or without contact, with actively infected TB patients were tested to detect LTBI. Our results show a significant difference between individuals in close contact with active TB patients pared to those without contact (3.2%), p < 0.01. The concordance between TST and QTB(®)-GIT was poor (κ = 0.31). Our preliminary results show that the QTB(®)-GIT has better capacity than TST to detect latent tuberculosis infection.
22099420
The β-propeller gene Rv1057 of Mycobacterium tuberculosis has a complex promoter directly regulated by both the MprAB and TrcRS two-component systems.
The β-propeller gene Rv1057 of Mycobacterium tuberculosis is activated by envelope stress and was first characterized as a regulatory target of the TrcRS ponent system (TCS). Rv1057 expression is repressed by TrcRS, and the Rv1057 proximal promoter contains a TrcR binding site. In this study, we determined that Rv1057 is also directly regulated by MprAB, a TCS associated with envelope stress. Multiple potential MprA binding sites (MprA boxes) were identified in the 1 kb intergenic region upstream of Rv1057, and four sites were shown to bind MprA. Although MprA boxes were found in the proximal promoter, analyses suggest that MprA and TrcR do pete for binding in this region. An MprAB-dependent, detergent-inducible transcriptional start point for Rv1057 was identified downstream of the MprA boxes, and a second TrcR binding site and small ORF of the 13E12 family were discovered in the distal promoter. MprAB was required for activation of Rv1057 during growth in macrophages and under detergent stress, and lacZ promoter constructs suggest the entire intergenic region is utilized during MprAB-dependent activation of Rv1057. These findings indicate that Rv1057 has an extensive plex promoter, and provide evidence for coordinated regulation of stress response genes by TCSs.
22099421
Activation of NK cell granulysin by mycobacteria and IL-15 is differentially affected by HIV.
NK cells play an important role in innate immunity to mycobacteria and are a significant source of the bactericidal effector molecule granulysin. Defects in NK cells have been described in HIV-infected patients, though mechanistic studies have focused on effector molecules relevant to anti-viral, and not anti-bacterial, function. Here we used primary NK cells from healthy human donors and an in vitro system to identify the phenotype of granulysin expressing NK cells, characterize activation stimuli that regulate granulysin, and to study the immediate effects of HIV on innate activation of NK cell granulysin expression. We observe that granulysin expression is co-associated with cytotoxicity receptors (NKp46, NKG2D) known to have important function in the cytotoxic response to M.tb-infected macrophages. Granulysin expression is significantly increased following exposure to IL-15 or Mycobacterium bovis BCG, but in contrast to our previous findings with CD8(+)T cells, expression is weakly activated by IL-21. Infection of PBMC with HIV-1 suppresses NK cell induction of granulysin by IL-15, but does not impair activation by BCG. These effects of HIV-1 are associated with reduced STAT5 phosphorylation in the IL-15 activated signaling cascade. These observations suggest that HIV may impair the anti-bacterial function of NK cells and have implications for clinical use of IL-15 to augment innate cell mediated immunity in HIV+ patients.
22099423
Adiponectin and atherosclerosis risk factors in African hemodialysis patients: a population at low risk for atherosclerotic cardiovascular disease.
Atherosclerotic cardiovascular disease (CVD) is the major cause of morbidity and mortality in hemodialysis (HD) patients. Adiponectin (ADPN), a recently discovered collagen-like protein, is secreted exclusively by adipocytes. It has anti-atherogenic properties and reduced serum ADPN levels have been shown to be predictive of cardiovascular events. In this study, we determined the atherosclerotic risk and the significance of ADPN levels in our HD patients and also examined its relationship to other traditional CVD risk factors. A cross-sectional study of 84 patients on maintenance HD (58 Blacks and 26 non-Blacks) and 63 healthy controls matched for age, sex and race (35 Blacks and 28 non-Blacks) was undertaken. Serum ADPN levels and other risk factors, including blood pressure, serum lipid, and C-reactive protein, were studied in HD patients and pared with the controls. Carotid artery intima-media thickness and plaque occurrence was measured by B-mode ultrasonography while echocardiography was done according to American Society of Echocardiography guidelines. Serum ADPN levels were higher in the HD pared with the control subjects (22.19 ± 0.98 mg/mL vs. 9.93 ± 0.68 mg/mL; P < 0.001). Higher ADPN levels in HD patients were associated with lower triglyceride levels. ADPN correlated positively (r = 0.49, P < 0.0001) with left ventricular mass index (LVMI) in the total study population. ADPN levels were raised in HD patients and correlated with LVMI, possibly because of the confounding effect of low glomerular filtration rate. ADPN levels were inversely related to risk factors for atherosclerosis and may provide possible targets for therapeutic interventions.
22099424
Cancers in patients with hemophilia: a retrospective study from the Italian Association of Hemophilia Centers.
The increased life expectancy of the hemophilia population, primarily as a result of advances in factor replacement therapy, has enabled hemophiliacs to reach an older age. Consequently, age-related diseases, such as cardiovascular disorders and cancers, are being increasingly recognized in such patients. However, only few data are available on such co-morbidities, their management and impact on the primary bleeding disorders.
22099425
Improvement of sulphur mustard-induced chronic pruritus, quality of life and antioxidant status by curcumin: results of a randomised, double-blind, placebo-controlled trial.
Skin is among the first and most heavily damaged organs upon sulphur mustard (SM) exposure. Pruritus is the mon chronic plication of SM, which adversely affects the quality of life (QoL). However, current therapies for the management of SM-induced pruritus are very limited and associated with side effects. The present trial investigated the efficacy of curcumin in the alleviation of SM-induced chronic pruritic symptoms. A total of ninety-six male Iranian veterans (age 37-59 years) were randomised to receive either curcumin (1 g/d, n 46) or placebo (n 50) for 4 weeks. Serum concentrations of substance P and activities of antioxidant enzymes were measured at baseline and at the end of the trial. Assessment of pruritus severity was performed using the pruritus score, visual analogue scale (VAS) and scoring atopic dermatitis (SCORAD) index. QoL was evaluated using the Dermatology Life Quality Index (DLQI) questionnaire. Serum concentrations of substance P (P<0·001) as well as activities of superoxide dismutase (P=0·02), glutathione peroxidase (P=0·006) and catalase (P<0·001) were significantly reduced in the curcumin group, while no significant change was observed in the placebo group. Curcumin supplementation was also associated with significant reductions in measures of pruritus severity including the pruritus score (P<0·001), VAS score (P<0·001), overall (P<0·001) and objective SCORAD (P=0·009), and DLQI's first question (P<0·001). None of these measures was significantly changed in the placebo group. As for the QoL, although DLQI scores decreased in both groups (P<0·001 and P=0·003 in the curcumin and placebo groups, respectively), the magnitude of reduction was significantly greater in the curcumin group (P<0·001). In conclusion, curcumin may be regarded as a natural, safe, widely available and inexpensive treatment for the management of SM-induced chronic pruritus.
22099430
Noninvasive assessment of endothelial function in clinical practice.
In the fight against cardiovascular diseases, preventive strategies are ing the focus of attention. One of these strategies proposes to identify individuals who are at a high risk of developing cardiovascular disease. Endothelial dysfunction could improve patient risk stratification and the implementation of preventive strategies. In this review we focus on noninvasive techniques that have recently e available to assess endothelial function: flow-mediated vasodilation as measured by ultrasound of the brachial artery, pulse wave analysis, and finger plethysmography during postischemic hyperemia. We describe the basic principles, the main protocols to perform these techniques, and their clinical value based on the scientific evidence.
22099431
Low frequency of human papillomavirus infection in conjunctival squamous cell carcinoma of Mexican patients.
The relationship between Human Papillomavirus (HPV) infection and conjunctiva cancer is controversial. HPV detection will provide more information about the role of this infectious agent in the biology of conjunctiva cancer. In the present study, DNA extracted and purified from 36 Conjunctival Squamous Cell Carcinomas (CSCC) was evaluated by PCR for HPV DNA sequences. The results were correlated with the clinical and histopathological variables.
22099433
Anemia and pregnancy: a link to maternal chronic diseases.
Anemia is a global public health problem. It has serious short- and long-term consequences during pregnancy and beyond. The anemic condition is often worsened by the presence of other chronic diseases such as malaria, tuberculosis, HIV, and diabetes. Untreated anemia also leads to increased morbidity and mortality from these chronic conditions as well. It is surprising that despite these chronic conditions (such as malaria, tuberculosis, and HIV) often being preventable, they still pose a real threat to public health. This article aims to review the current understanding of the pathophysiology, risks, prevention, and treatment of anemia in the light of these chronic conditions.
22099434
Physiological adaption to maternal malaria and other adverse exposure: low birth weight, functional capacity, and possible metabolic disease in adult life.
The concept of developmental origins of health and disease and the epidemic of municable diseases in low- and e countries has increased the focus on low birth weight (LBW). Most studies linking LBW to future risk of metabolic diseases have focused on maternal nutrition and anemia. Several studies have shown that LBWis linked to skeletal muscle insulin resistance and future risk of type 2 diabetes, possibly caused by permanent modifications in skeletal muscle morphology and biochemistry leading to lowered functional capacity and physical activity in adult life. In some parts of the world, malaria infection during pregnancy is the mon cause of anemia and LBW. By causing disruption to nutrient supply, as well as hypoxia, placental malaria and anemia negatively impact intrauterine fetal development. Thus, in utero exposure to placental malaria and consequent LBW may impart a higher risk of developing type 2 diabetes in early adult life. This has not been investigated systematically. Worldwide, an estimated 125 million pregnancies occur annually in malarial areas with a vast potential for intrauterine growth restriction, LBW, and subsequent risk of metabolic dysfunction, including type 2 diabetes; this potential link also opens an opportunity for early prevention of future metabolic diseases by paying greater attention to malaria during pregnancy.
22099435
Development of a model to assess the cost-effectiveness of gestational diabetes mellitus screening and lifestyle change for the prevention of type 2 diabetes mellitus.
Gestational diabetes mellitus (GDM) is increasingly recognized as an opportunity for early prevention of diabetes and other diseases over the lifespan, and may be responsible for up to 30% of cases of type 2 diabetes. A newly developed mathematical model (the GDModel) provides provisional estimates of the cost and health impact of various GDM screening and management choices, and calculates averted disability-adjusted life-years (DALYs). The model was piloted in 5 different healthcare facilities in India and Israel. Universal screening of pregnant women followed by postpartum lifestyle management yielded net savings of US$78 per woman with GDM in India and US$1945 per woman in Israel. The estimated DALYs averted were 2.33 in India and 3.10 in Israel. With lower GDM prevalence, intervention efficacy, and type 2 diabetes incidence, the intervention had a net cost in India, with a cost per DALY averted of US$11.32. This was far below the WHO definition of "very cost-effective," set at annual GDP per capita. The intervention in Israel remained cost-saving. GDM screening and postpartum lifestyle management are either cost-saving or have a net cost but an attractive cost-effectiveness ratio. Some input values are currently being refined. Nevertheless, the current findings of cost-savings or favorable cost-effectiveness are robust to a wide range of plausible input values, including highly unfavorable values. The GDModel will be further developed into a user-friendly tool that can guide policy-makers on decisions regarding GDM screening strategies and guidelines.
22099436
Matching diagnosis and management of diabetes in pregnancy to local priorities and resources: an international approach.
The International Association of the Diabetes and Pregnancy Study Groups' (IADPSG) criteria for the diagnosis and classification of hyperglycemia in pregnancy are described and application of these in differing healthcare contexts on a worldwide basis is reported. Existing local protocols and known epidemiologic and clinical data regarding the detection and management of overt diabetes and gestational diabetes in the context of human pregnancy are considered. Although the IADPSG criteria are uniform, their introduction poses a variety of practical and technical challenges in differing healthcare contexts, both between and within countries. Knowledge of local factors will be vital in the implementation of the new guidelines and will require extensive liaison with local clinical and health policy groups. Resource availability will be critical in determining the type of treatment available in this context. The IADPSG criteria offer an important opportunity for a uniform approach to diabetes in pregnancy. Scaled implementation of these criteria adapted to a variety of local healthcare contexts should improve both research endeavors and patient care.
22099437
Developmental origins of health and disease: moving from biological concepts to interventions and policy.
The rising incidence of municable diseases (NCDs), especially in young adults, presents great humanitarian and economic challenges to high-resource and, increasingly, to low-resource countries. No longer considered to be diseases of affluence, NCDs are exacerbated by urbanization and changes in social and lifestyle factors such as diet and family size. New research emphasizes the importance of early life factors in establishing the risk of NCDs through inadequate responses to later challenges, such as an obesogenic environment. A new focus on interventions to promote a good start to life in at-risk populations necessitates revision of public health policy, with implications for the health, education, and empowerment of women and children in particular.
22099438
Gestational diabetes screening: the low-cost algorithm.
The American Diabetes Association has endorsed the demanding mendation by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) that every pregnant woman should undergo the oral glucose tolerance test (OGTT) for the screening of gestational diabetes mellitus (GDM). The aim of this study was to find out if the fasting plasma glucose (FPG) and newer emerging technologies could simplify the cumbersome IADPSG algorithm. Two FPG thresholds (of the OGTT) were used to rule in and rule out GDM in the Hyperglycemia and Adverse Pregnancy e (HAPO) cohort (n = 23316) and a population at high risk for GDM (n = 10283). For the HAPO cohort and the high-risk population, respectively, FPG thresholds of: (a) ≥ 5.1 mmol/L (specificity 100%) independently ruled in GDM in 1769 (8.3%) women and 2975 (28.9%) women; and (b) ≤ 4.4 mmol/L ruled out GDM in 11526 (49.4%) women (84.1% sensitivity) and 2228 (21.7%) women (95.4% sensitivity). Use of the FPG independently could have avoided 13295 (57.0%) and 5203 (50.6%) OGTTs in the 2 groups. The initial FPG-by significantly reducing the number of cumbersome OGTTs needed-can make the IADPSG mendations more acceptable worldwide. The number of GDM women missed is population dependent. For low-resource countries, alternative newer and cheaper tests in development hold an exciting future.
22099439
Integrating noncommunicable disease prevention into maternal and child health programs: can it be done and what will it take?
municable diseases (NCDs) are the leading cause of mortality worldwide. However, these diseases have not been adequately addressed by health systems, especially in low-resource countries. Similarly, there is no equitable allocation of global resources for mensurate with the burden of diseases occasioned by NCDs. This has resulted in poor access to care for women, girls, and other vulnerable groups affected by NCDs. Owing to their position in most societies, women lack control over resources and, hence, cannot afford quality care to treat NCDs. Women also face sociocultural, geographic, and economic barriers to access to care. They are less recognized and catered for in terms of prehensiveness, and responsiveness of healthcare systems. Considering that NCDs affect women more than the general population, tackling them as part of an integrated program for women's health will improve the coverage of the most vulnerable groups. This paper describes how NCD prevention and control could be integrated into maternal and child health programs to improve access to NCD services. It presents the effectiveness, benefits, and challenges of this approach when applied at the primary healthcare level.
22099440
Designing feasible interventions for healthy pregnancies in low-resource settings.
In low-resource settings there is a need for effective interventions targeting women before and during pregnancy to improve their health es and provide the best start to life for their infants. The aim of this paper is to provide an overview for designing, implementing, and evaluating such interventions. Drawing upon published literature and case studies, several key steps in the process of intervention design, implementation, and evaluation are identified. Pregnancy intervention studies in low-resource settings are challenging. Essential intervention process steps include: (1) selecting the optimal setting to pilot the intervention; (2) forming strong stakeholder collaborations; (3) identifying, understanding, and munity health problems; (4) facilitating the demand for intervention research and evidence utilization; (5) effectively implementing and evaluating the prototype intervention to provide evidence of effectiveness; and (6) planning with stakeholders for sustainability. Fundamental to any intervention for healthy pregnancies is the understanding that the process does not end with an evaluation study, but rather the end goal is to ensure successful interventions are sustainable, scalable, and integrated into health services.
22099441
Gestational diabetes mellitus: advocating for policy change in India.
A multimedia awareness and advocacy campaign for mainstreaming gestational diabetes mellitus (GDM) in the public health domain is described. The multimedia campaign has created awareness about the relevance of GDM to women's health and the health of future generations through direct contact, reaching out to over half a million people in 7 districts of 4 states in northern India. Using mass media, over 3.7 million people have received information on GDM. Through multistakeholder forums, more than 1000 key stakeholders have been encouraged to mainstream GDM into the existing health delivery system. The Indian Ministry of Health has introduced free screening for GDM among the 5 services offered to pregnant women below the poverty line in the National Rural Health Mission (NRHM) program. In addition, several state governments, such as in Bihar, Delhi, Jharkhand, and Punjab, have pledged similar initiatives addressing GDM; the Government of Tamil Nadu is already implementing such a policy. Policy development is plex process that requires action on many fronts. By showcasing evidence, raising awareness, creating public opinion through dialogue and discussion, media can help build a positive environment and momentum for effective policy creation as well as service utilization.
22099442
Global adaptation of IADPSG recommendations: a national approach.
The current practice for diagnosing gestational diabetes mellitus (GDM) in Israel employs a two-step screening approach using a 50 g glucose challenge test (GCT) followed by a 3-hour 100 g oral glucose tolerance test (OGTT). The overall adherence to this process is more than 90%. Recently, the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) mended changing this practice to a single-step GDM screening, employing a 75 g OGTT. New plasma glucose cutoffs were mended. To make mendations for a new screening and diagnosis policy for GDM in Israel, mittee was assembled, including representatives of professional medical organizations, health maintenance organizations (HMOs), health policy makers, epidemiologists and biostatisticians. There was agreement that a consensus can be achieved only by clinical evidence and that consensus is a key factor for changing health policy. It was also realized that the availability of local data on the annual rates of GDM, plications, and cost-effectiveness of screening and treatment are suboptimal. This generated two studies: the first provided additional analyses of data concerning Israeli women participating in the Hyperglycemia and Adverse Pregnancy e (HAPO) study, and the second was a cost-effectiveness analysis based on Clalit Health Service's (the largest HMO in the country) database. We found that the prevalence of GDM in Israel is approximately 6% and is expected to increase to 9% by adopting the new IADPSG mendations. The conclusion was that a one-step approach is presumed to be not only cost-effective but cost-saving, even under conservative estimates. We mend such a process for other countries debating whether to change their GDM screening and diagnostic approach.
22099445
Taking on the challenge of noncommunicable diseases: we all hold a piece of the puzzle.
Two out of 3 deaths globally are attributable to municable diseases (NCDs), with 80% occurring in low-resource countries. The "cost of inaction" is estimated to be US$35 trillion between 2005 and 2030. We need to get behind the societal root causes of this global health challenge; we need a life-course approach to respond to the increasing evidence of intergenerational transmission of NCDs; and we need to focus on strengthening of health systems and integration of services for prevention, screening, and management across disease groups. There is a growing understanding that all actors, private or public, for-profit or not-for-profit, can make substantial and positive contributions as long as they maintain transparency in their agenda, motivation, and actions. Effective and sustainable global public-private partnerships require trust between partners, a safe space for talks and negotiations, and a framework for governance and accountability. We need a neutral global convener to unite us all behind shared visions for a healthier future, where each player is encouraged mit and contribute to mon cause and be recognized or held accountable for their mitments. Creation of such a platform could be a direct e of the United Nations High Level Meeting on NCDs to be held in September 2011.
22099446
Maternal obesity: implications for pregnancy outcome and long-term risks-a link to maternal nutrition.
As obesity es a worldwide epidemic, its prevalence during reproductive age is also increased. Alarming reports state that two-thirds of adults in the USA are overweight or obese, with half of them in the latter category, and the rate of obese pregnant women is estimated at 18-38%. These women are of major concern to women's health providers because they encounter numerous plications. Obesity-related reproductive plications range from infertility to a wide spectrum of diseases such as hypertensive disorders, coagulopathies, gestational diabetes mellitus, plications, and plications such as large-for-gestational-age infants, congenital malformations, stillbirth, and shoulder dystocia. Recent reports suggest that obesity during pregnancy can be a risk factor for developing obesity, diabetes, and cardiovascular diseases in the newborn later in life. This review will address the implication of obesity on pregnancy and child health, and explore recent literature on obesity during pregnancy.
22099447
X-ray fluorescence in investigations of cultural relics and archaeological finds.
Some characteristic features of X-ray fluorescence (XRF) analysis make it an ideal method for investigations of cultural relics and archaeological finds. It has therefore e a standard method used in archaeometry. Paintings, frescos, manuscripts, pottery, metalwork, glass, and many other objects are analysed with the aim of recognising their materials, production technologies and origin, and for identifying counterfeits. This paper reviews various techniques used in XRF analyses of works of art, summarises the advantages and limitations of the method, and presents some typical examples of its use. The general review is supplemented by some techniques used and some results achieved at CTU-FNSPE in Prague.
22099448
Development of a validated patient-reported symptom metric for pediatric eosinophilic esophagitis: qualitative methods.
Previous attempts to measure symptoms in pediatric Eosinophilic Esophagitis (EoE) have not fully included patients and parents in the item development process. We sought to identify and validate key patient self-reported and parent proxy-reported es (PROs) specific to EoE.
22099449
Selling sex in unsafe spaces: sex work risk environments in Phnom Penh, Cambodia.
The risk environment framework provides a valuable but under-utilised heuristic for understanding environmental vulnerability to HIV and other sexually transmitted infections among female sex workers. Brothels have been shown to be safer than street-based sex work, with higher rates of consistent condom use and lower HIV prevalence. While entertainment venues are also assumed to be safer than street-based sex work, few studies have examined environmental influences on vulnerability to HIV in this context.
22099450
Vitiligo as an inflammatory skin disorder: a therapeutic perspective.
From a therapeutic standpoint, vitiligo is still regarded by many physicians as a simple problem of regenerative medicine, with the main aim to repopulate the depigmented skin with functional melanocytes from the margins of the lesions or from intact progenitors in hair follicles. However, recent research in vitiligo suggests that various local triggers alert the skin immune innate system and may precede adaptive immune responses targeting melanocytes. This scenario is close to that of mon skin inflammatory disorders like psoriasis and atopic, and suggests to target as a priority this clinically silent ponent of he disease. This perspective highlights possible targets for intervention.
22099451
Identification of Tyr74 and Tyr177 as substrate oxidation sites in cationic cell wall-bound peroxidase from Populus alba L.
Cationic cell wall-bound peroxidase (CWPO-C) has the capability to oxidize sinapyl alcohol, ferrocytochrome c, and synthetic lignin polymers, unlike most peroxidases that have been characterized in flowering plants, such as horseradish peroxidase and Arabidopsis thaliana peroxidase A2. It has been suggested that the oxidation site is located on the CWPO-C surface, and homology modeling and chemically modified CWPO-C studies suggest that Tyr74 and/or Tyr177 are possible participants in the catalytic site. The present study clarifies the importance of these Tyr residues for substrate oxidation, using binant CWPO-C and binant mutant CWPO-C with phenylalanine substitution(s) for tyrosine. Such binant proteins, produced in Escherichia coli as inclusion bodies, were successfully refolded to yield the active form, and purified binant protein solutions exhibited typical spectra of high-spin ferric protein and displayed H(2) O(2) -dependent oxidation of guaiacol, 2,6-dimethoxyphenol, and syringaldazine. Measurement of peroxidase activity with these guaiacyl and pounds as reducing substrates indicated that a single mutation, Y74F or Y177F, resulted in substantial loss of oxidation activity (∼ 40-60% and 82%, respectively). Also, over 95% of the oxidation activity was lost with a double mutation, Y74F/Y177F. These results indicated that Tyr74 and Tyr177, rather than the heme pocket, play a central role in the oxidation of these substrates. This is the first report of active residues on an enzyme surface being identified in a plant peroxidase. This study also suggests that sinapyl alcohol incorporation into lignin is performed by a peroxidase that generates Tyr radicals on its surface.
22099452
Mapping genetic influences on cortical regionalization.
In this issue of Neuron, Chen and bine structural MRI and a twin-study design to investigate the influence of genetics on human cortical regionalization. Their results resonate with findings from animal studies and certain human syndromes of developmental cortical malformation.
22099453
DISC1: a schizophrenia gene with multiple personalities.
Two papers address the contribution of DISC1 to neural development and schizophrenia risk in this issue of Neuron. plementary studies elegantly bridge the gap between genetic and cellular studies of schizophrenia, providing a level of functional validation that is often lacking in the field.
22099454
A surprisingly singular role for endophilin in synaptic vesicle recycling.
Synaptic vesicle endocytosis requires membrane curvature, fission, and uncoating. Endophilin has been proposed to play a role in all three steps, but in this issue of Neuron, De Camilli and colleagues show that at mammalian central synapses it is primarily involved in clathrin uncoating.
22099455
Cortical processing of odor objects.
Natural odors, posed of many ponents, are analyzed by peripheral receptors ponent features and translated into spatiotemporal patterns of neural activity in the olfactory bulb. Here, we will discuss the role of the olfactory cortex in the recognition, separation pletion of those odor-evoked patterns, and how these processes contribute to odor perception. Recent findings regarding the neural architecture, physiology, and plasticity of the olfactory cortex, principally the piriform cortex, will be described in the context of how this paleocortical structure creates odor objects.
22099456
Memory: enduring traces of perceptual and reflective attention.
Attention and memory are typically studied as separate topics, but they are highly intertwined. Here we discuss the relation between memory and two fundamental types of attention: perceptual and reflective. Memory is the persisting consequence of cognitive activities initiated by and/or focused on external information from the environment (perceptual attention) and initiated by and/or focused on internal mental representations (reflective attention). We consider three key questions for advancing a cognitive neuroscience of attention and memory: to what extent do perception and reflection share representational areas? To what extent are the control processes that select, maintain, and manipulate perceptual and reflective information subserved mon areas and networks? During perception and reflection, to what extent mon areas responsible for binding features together to plex, episodic memories and for reviving them later? Considering similarities and differences in perceptual and reflective attention helps integrate a broad range of findings and raises important unresolved issues.
22099457
Genetic influences on cortical regionalization in the human brain.
Animal data demonstrate that the development of distinct cortical areas is influenced by genes that exhibit highly regionalized expression patterns. In this paper, we show genetic patterning of cortical surface area derived from MRI data from 406 adult human twins. We mapped genetic correlations of areal expansion between selected seed regions and all other cortical locations, with the selection of seed points based on results from animal studies. "Marching seeds" and a data-driven, hypothesis-free, fuzzy-clustering approach provided convergent validation. The results reveal strong anterior-to-posterior graded, bilaterally symmetric patterns of regionalization, largely consistent with patterns previously reported in nonhuman mammalian models. Broad similarities in genetic patterning between rodents and humans might suggest a conservation of cortical patterning mechanisms, whereas dissimilarities might reflect the functionalities most essential to each species.
22099460
An imbalancing act: gap junctions reduce the backward motor circuit activity to bias C. elegans for forward locomotion.
A neural network can sustain and switch between different activity patterns to execute multiple behaviors. By monitoring the decision making for directional otion through motor circuit calcium imaging in behaving Caenorhabditis elegans (C. elegans), we reveal that C. elegans determines the directionality of movements by establishing an imbalanced output between the forward and backward motor circuits and that it alters directions by switching between these imbalanced states. We further demonstrate that premotor interneurons modulate endogenous motoneuron activity to establish the output imbalance. Specifically, the UNC-7 and UNC-9 innexin-dependent premotor interneuron-motoneuron coupling prevents a balanced output state that leads to movements without directionality. Moreover, they act as shunts to decrease the backward-circuit activity, establishing a persistent bias for the high forward-circuit output state that results in the inherent preference of C. elegans for forward otion. This study demonstrates that imbalanced motoneuron activity underlies directional movement and establishes gap junctions as critical modulators of the properties and outputs of neural circuits.
22099458
Common DISC1 polymorphisms disrupt Wnt/GSK3β signaling and brain development.
Disrupted in Schizophrenia-1 (DISC1) is a candidate gene for psychiatric disorders and has many roles during brain development. Common DISC1 polymorphisms (variants) are associated with neuropsychiatric phenotypes including altered cognition, brain structure, and function; however, it is unknown how this occurs. Here, we demonstrate using mouse, zebrafish, and human model systems that DISC1 variants are loss of function in Wnt/GSK3β signaling and disrupt brain development. The DISC1 variants A83V, R264Q, and L607F, but not S704C, do not activate Wnt pared with wild-type DISC1 resulting in decreased neural progenitor proliferation. In zebrafish, R264Q and L607F could not rescue DISC1 knockdown-mediated aberrant brain development. Furthermore, human lymphoblast cell lines endogenously expressing R264Q displayed impaired Wnt signaling. Interestingly, S704C inhibited the migration of neurons in the developing neocortex. Our data demonstrate DISC1 variants impair Wnt signaling and brain development and elucidate a possible mechanism for their role in neuropsychiatric phenotypes.
22099461
Recruitment of endophilin to clathrin-coated pit necks is required for efficient vesicle uncoating after fission.
Endophilin is a membrane-binding protein with curvature-generating and -sensing properties that participates in clathrin-dependent endocytosis of synaptic vesicle membranes. Endophilin also binds the GTPase dynamin and the phosphoinositide phosphatase synaptojanin and is thought to coordinate constriction of coated pits with membrane fission (via dynamin) and subsequent uncoating (via synaptojanin). We show that although synaptojanin is recruited by endophilin at bud necks before fission, the knockout of all three mouse endophilins results in the accumulation of clathrin-coated vesicles, but not of clathrin-coated pits, at synapses. The absence of endophilin impairs but does not abolish synaptic transmission and results in perinatal lethality, whereas partial endophilin absence causes severe neurological defects, including epilepsy and neurodegeneration. Our data support a model in which endophilin recruitment to coated pit necks, because of its curvature-sensing properties, primes vesicle buds for subsequent uncoating after membrane fission, without being critically required for the fission reaction itself.
22099462
XPORT-dependent transport of TRP and rhodopsin.
TRP channels have emerged as key biological sensors in vision, taste, olfaction, hearing, and touch. Despite their importance, virtually nothing is known about the folding and transport of TRP channels during biosynthesis. Here, we identify XPORT (exit protein of rhodopsin and TRP) as a critical chaperone for TRP and its G protein-coupled receptor (GPCR), rhodopsin (Rh1). XPORT is a resident ER and secretory pathway protein that interacts with TRP and Rh1, as well as with Hsp27 and Hsp90. XPORT promotes the targeting of TRP to the membrane in Drosophila S2 cells, a finding that provides a critical first step toward solving a longstanding problem in the successful heterologous expression of TRP. Mutations in xport result in defective transport of TRP and Rh1, leading to retinal degeneration. Our results identify XPORT as a molecular chaperone and provide a mechanistic link between TRP channels and their GPCRs during biosynthesis and transport.
22099459
Interaction between FEZ1 and DISC1 in regulation of neuronal development and risk for schizophrenia.
Disrupted-in Schizophrenia 1 (DISC1), a susceptibility gene for major mental disorders, encodes a scaffold protein that has a multifaceted impact on neuronal development. How DISC1 regulates different aspects of neuronal development is not well understood. Here, we show that Fasciculation and Elongation Protein Zeta-1 (FEZ1) interacts with DISC1 to synergistically regulate dendritic growth of newborn neurons in the adult mouse hippocampus, and that this plements a parallel DISC1-NDEL1 interaction that regulates cell positioning and morphogenesis of newborn neurons. Furthermore, genetic association analysis of two independent cohorts of schizophrenia patients and healthy controls reveals an epistatic interaction between FEZ1 and DISC1, but not between FEZ1 and NDEL1, for risk of schizophrenia. Our findings support a model in which DISC1 regulates distinct aspects of neuronal development through its interaction with different intracellular partners and such epistasis may contribute to increased risk for schizophrenia.
22099463
Activation of central orexin/hypocretin neurons by dietary amino acids.
Hypothalamic orexin/hypocretin (orx/hcrt) neurons regulate energy balance, wakefulness, and reward; their loss produces narcolepsy and weight gain. Glucose can lower the activity of orx/hcrt cells, but whether other dietary macronutrients have similar effects is unclear. We show that orx/hcrt cells are stimulated by nutritionally relevant mixtures of amino acids (AAs), both in brain slice patch-clamp experiments, and in c-Fos expression assays following central or peripheral administration of AAs to mice in vivo. Physiological mixtures of AAs electrically excited orx/hcrt cells through a dual mechanism involving inhibition of K(ATP) channels and activation of system-A amino acid transporters. Nonessential AAs were more potent in activating orx/hcrt cells than essential AAs. Moreover, the presence of physiological concentrations of AAs suppressed the glucose responses of orx/hcrt cells. These results suggest a new mechanism of hypothalamic integration of macronutrient signals and imply that orx/hcrt cells sense macronutrient balance, rather than net energy value, in extracellular fluid.
22099464
Bidirectional regulation of dendritic voltage-gated potassium channels by the fragile X mental retardation protein.
How transmitter receptors modulate neuronal signaling by regulating voltage-gated ion channel expression remains an open question. Here we report dendritic localization of mRNA of Kv4.2 voltage-gated potassium channel, which regulates synaptic plasticity, and its local translational regulation by fragile X mental retardation protein (FMRP) linked to fragile X syndrome (FXS), the mon heritable mental retardation. FMRP suppression of Kv4.2 is revealed by elevation of Kv4.2 in neurons from fmr1 knockout (KO) mice and in neurons expressing Kv4.2-3'UTR that binds FMRP. Moreover, treating hippocampal slices from fmr1 KO mice with Kv4 channel blocker restores long-term potentiation induced by moderate stimuli. Surprisingly, recovery of Kv4.2 after N-methyl-D-aspartate receptor (NMDAR)-induced degradation also requires FMRP, likely due to NMDAR-induced FMRP dephosphorylation, which turns off FMRP suppression of Kv4.2. Our study of FMRP regulation of Kv4.2 deepens our knowledge of NMDAR signaling and reveals a FMRP target of potential relevance to FXS.
22099465
Increased size and stability of CA1 and CA3 place fields in HCN1 knockout mice.
Hippocampal CA1 and CA3 pyramidal neuron place cells encode the spatial location of an animal through localized firing patterns called "place fields." To explore the mechanisms that control place cell firing and their relationship to spatial memory, we studied mice with enhanced spatial memory resulting from forebrain-specific knockout of the HCN1 hyperpolarization-activated cation channel. HCN1 is strongly expressed in CA1 neurons and in entorhinal cortex grid cells, which provide spatial information to the hippocampus. Both CA1 and CA3 place fields were larger but more stable in the knockout mice, with the effect greater in CA1 than CA3. As HCN1 is only weakly expressed in CA3 place cells, their altered activity likely reflects loss of HCN1 in grid cells. The more pronounced changes in CA1 likely reflect the intrinsic contribution of HCN1. The enhanced place field stability may underlie the effect of HCN1 deletion to facilitate spatial learning and memory.
22099466
Dissociable reward and timing signals in human midbrain and ventral striatum.
Reward prediction error (RPE) signals are central to current models of reward-learning. Temporal difference (TD) learning models posit that these signals should be modulated by predictions, not only of magnitude but also timing of reward. Here we show that BOLD activity in the VTA conforms to such TD predictions: responses to unexpected rewards are modulated by a temporal hazard function and activity between a predictive stimulus and reward is depressed in proportion to predicted reward. By contrast, BOLD activity in ventral striatum (VS) does not reflect a TD RPE, but instead encodes a signal on the variable relevant for behavior, here timing but not magnitude of reward. The results have important implications for dopaminergic models of cortico-striatal learning and suggest a modification of the conventional view that VS BOLD necessarily reflects inputs from dopaminergic VTA neurons signaling an RPE.
22099468
P-selectin, E-selectin, and CD40L over time in chronic hemodialysis patients.
The aim of this study was to measure P-selectin, E-selectin, and CD-4L levels over time in chronic hemodialysis (HD) patients. Thirty stable patients with end-stage renal failure undergoing chronic HD were included in the study. Blood samples were obtained before HD for measurement of P-selectin, E-selectin, and CD-40L. Measurements were performed at month 0 (T0), 3 (T2), 8 (T3), and 13 (T4). The levels of P-selectin, E-selectin, and CD40L were also analyzed according to the occurrence of cardiovascular disease (CVD) and to CVD-related mortality. The levels of CD40L and P-selectin changed significantly over time, decreasing at month 3 and 6 and returning at the T0 levels at month 13. Conversely, E-selectin levels did not. The levels of CD40L, P-selectin and E-selectin over time did not differ significantly between patients with age ≤ 65 or > 65 years, between patients with or without CVD, or between patients who died or who survived during the follow-up. In end-stage renal failure patients undergoing chronic HD, CD40L and P-selectin, but not E-selectin, showed a transient decrease over time, and the serum levels of these molecules were not associated with CVD or with CVD-related mortality.
22099467
Functional network organization of the human brain.
plex systems may be mathematically modeled as graphs, revealing properties of the system. Here we study graphs of functional brain organization in healthy adults using resting state functional connectivity MRI. We propose two novel brain-wide graphs, one of 264 putative functional areas, the other a modification of voxelwise networks that eliminates potentially artificial short-distance relationships. These graphs contain many subgraphs in good agreement with known functional brain systems. Other subgraphs lack established functional identities; we suggest possible functional characteristics for these subgraphs. Further, graph measures of the areal network indicate that the default mode subgraph shares network properties with sensory and motor subgraphs: it is internally integrated but isolated from other subgraphs, much like a "processing" system. The modified voxelwise graph also reveals spatial motifs in the patterning of systems across the cortex.
22099469
A self-directed adherence management program for patients with heart failure completing combined aerobic and resistance exercise training.
This study measured the impact of the Exercise Adherence Management Program (EAMP) provided to 20 patients with heart failure (HF) who participated in bined resistance and aerobic exercise training program during two 12-week phases. The EAMP included strategies designed to support exercise self-efficacy and adherence. Results indicate that an improvement in exercise self-efficacy occurred during the study period, whereas exercise adherence declined during the unsupervised phase. The highest rated adherence strategy for helpfulness and self-efficacy was group sessions. The study supports the use of adherence strategies based on self-efficacy in exercise programs for patients with HF.
22099470
Nurses' perceptions of how physical environment affects medication errors in acute care settings.
The work that nurses perform in hospital environments is physically and psychologically intense, with the potential for burnout and stress. This issue pounded by crowded and poorly designed work spaces in nursing units that can contribute to medical mistakes, including medication errors. This article is based on a study that examined the nurses' perception of how the physical environment in hospitals affects medication errors. Literature suggests that reduction of staff stress can be achieved through physical environmental considerations, such as improved air quality, acoustics, and lighting. However, there is no empirical study specifically exploring the relationship between aspects of the physical environment and medication errors. In this study, a cross-sectional survey was conducted with nursing staff (N = 84) in four hospitals in the Pacific Northwest region of the United States. The survey included questions on nursing unit design, medication room configurations, perceived incidence of errors, and adverse events. Respondents noted several physical environmental factors that are potentially problematic in the nursing station area and can lead to medication, documentation, and other types of nursing errors. These factors include inadequate space in charting and documentation area, lengthy walking distances to patient rooms, insufficient patient surveillance opportunity/lack of visibility to all parts of the nursing unit, small size of the medication room, inappropriate organization of medical supplies, high noise levels in nursing unit, poor lighting, and lack of privacy in the nursing stations. As administrators in acute care facilities consider strategies for organizational and staff interventions to reduce medication errors, it is important to consider physical environmental factors to have prehensive understanding of the issue.
22099471
Comparison of oxygen saturation values and measurement times by pulse oximetry in various parts of the body.
The aim of this study, which included 40 patients, was pare the values pulse oximetry and the measurement times in various regions of the body. Data were analyzed using intraclass correlation coefficient test and paired-sample test. The confidence power value was found to be .81 for parison of oxygen saturation values by arterial blood gas analysis and measurement by the forehead probe. It was found that the time for oxygen saturation measurement using the forehead probe was shorter than those using the finger and toe probes.
22099472
Binding of oxindole-Schiff base copper(II) complexes to DNA and its modulation by the ligand.
Previous studies on plexes with oxindole-Schiff base ligands have shown their potential antitumor activity towards different cells, inducing apoptosis through a preferential attack to DNA and/or mitochondria. Herein, we better characterize the interactions between some of these plexes and DNA. Investigations on its binding ability to DNA were carried out by fluorescence measurements petitive experiments with ethidium bromide, using plasmidial or calf-thymus DNA. These results indicated an efficient binding process similar to that observed with copper(II)-phenanthroline species, [Cu(o-phen)(2)](2+), with binding constants in the range 3 to 9×10(2) M(-1). DNA cleavage experiments in the presence and absence of distamycin, a recognized binder of DNA, indicated that this binding probably occurs at major or minor groove, leading to double-strand DNA cleavage, and being modulated by the imine ligand. Corroborating these data, discrete changes in EPR spectra of the plexes were observed in the presence of DNA, while more remarkable changes were observed in the presence of nucleotides (AMP, GMP, CMP or UMP). Additional evidence for preferential coordination of the copper centers to the bases guanine or cytosine was obtained from titrations of plexes with each nucleotide, monitored by absorption spectral changes. Therefore, the obtained data point out to their action as groove binders to DNA bases, rather than as intercalators or covalent cross-linkers. Further investigations by SDS PAGE using (32)P-ATP or (32)P-oligonucleotides attested that no hydrolysis of phosphate linkage in DNA or RNA occurs, in the presence of plexes, confirming their main oxidative mechanism of action.
22099473
Interaction of arsenite with a zinc finger CCHC peptide: evidence for formation of an As-Zn-peptide mixed complex.
The interaction of arsenite with a Cys(3)His (CCHC) zinc finger model (34-51) HIV-1 nucleocapsid protein p7 (NCp7) peptide in the absence and presence of Zn(II) was studied using fluorescence spectroscopy, CD (circular dichroism) and ESI-MS (Electrospray Ionization Mass Spectrometry). We found that arsenic forms plexes with the free peptide and the zinc finger peptide. In the former case the peptide conformation differed greatly from that of the zinc finger, whereas in the second case a mixed plex was formed with partial preservation of zinc finger conformation. An apparent stability constant was estimated for the mixed plex (K=2083 M(-1) and 442 M(-1) at 25°C and pHs 6 and 7, respectively). Our study also shows that the interaction of arsenic with the CCHC motif is facilitated by glutathione (GSH), through formation of a GS-As-peptide conjugate.
22099474
Schizophrenia, culture and neuropsychology: sensory deficits, language impairments and social functioning in Chinese-speaking schizophrenia patients.
While 20% of schizophrenia patients worldwide speak tonal languages (e.g. Mandarin), studies are limited to Western-language patients. Western-language patients show tonal deficits that are related to impaired emotional processing of speech. However, language processing is minimally affected. In contrast, in Mandarin, syllables are voiced in one of four tones, with word meaning varying accordingly. We hypothesized that Mandarin-speaking schizophrenia patients would show impairments in underlying basic auditory processing that, unlike in Western groups, would relate to deficits in word recognition and social es.
22099475
Decoding the molecular design principles underlying Ca(2+) binding to βγ-crystallin motifs.
Numerous proteins belonging to the recently expanded βγ-crystallin superfamily bind Ca(2+) at the double-clamp N/D-N/D-X(1)-X(2)-S/T-S motif. However, there have been no attempts to understand the intricacies involving Ca(2+) binding, such as the determinants of Ca(2+)-binding affinity and their contributions to gain in stability. This work is an in-depth analysis of understanding the modes and determinants of Ca(2+) binding to βγ-crystallin motifs. We have performed extensive naturally occurring substitutions from related proteins on the βγ-crystallin domains of flavollin, a low-affinity Ca(2+)-binding protein, and clostrillin, a moderate-affinity protein. We monitored the consequences of these modifications on Ca(2)(+) binding by isothermal titration calorimetry, thermal stability and conformational and crystal structure analyses. We demonstrate that Ca(2)(+) binding to the two sites of a βγ-domain is interdependent and that the presence of Arg at the fifth position disables a site. A change from Thr to Ser, or vice versa, influences Ca(2+)-binding affinity, highlighting the basis of diversity found in these domains. A subtle change in the first site has a greater influence on Ca(2)(+) binding than a similar alteration in the second site. Thus, the second site is more variable in nature. Replacing an acidic or hydrophobic residue in a binding site alters the Ca(2+)-binding properties drastically. While it appears from their binding site sequence that these domains have evolved randomly, our examination illustrates the subtlety in the design of these modules. Decoding such design schemes would aid in our understanding of the functional themes underlying differential Ca(2)(+) binding and in predicting these in emerging sequence information.
22099476
Lower urinary tract symptoms after feminizing genitoplasty.
To investigate the prevalence of lower urinary tract symptoms (LUTS) in a Finnish cohort of patients who had undergone feminizing genitoplasty in childhood.
22099477
Tamsulosin for the management of distal ureteral stones in children: a prospective randomized study.
Based on efficacy demonstrated in the adult population, tamsulosin was evaluated with regard to facilitating ureteral stone expulsion in children presenting with distal ureteric calculi.
22099478
Effect of increased intra-abdominal pressure on urinary system development in fetal rabbits.
To investigate the effect of increased intra-abdominal pressure (IAP) on the fetal urinary system.
22099479
Religiousness, mental health, and quality of life in Brazilian dialysis patients.
Patients with chronic kidney disease often use religion as a coping strategy to relieve suffering and serve as a source of strength. The aim of this study was to identify religious aspects associated with mental health and quality of life in Brazilian dialysis patients. A cross-sectional study was performed involving two dialysis centers in Brazil. Patients were selected consecutively over three typical dialysis treatment days. The questionnaire was self-administered and covered the following aspects: socio-demographic aspects, religiousness (using the Portuguese version of the Private and Social Religious Practice Scale), quality of life (World Health Organization Quality of Life brief Scale Brief Version), depression and anxiety (Beck Inventory), and pain grade. For statistical analysis, the hypothesis that different religious variables are associated (positively or negatively) with depressive/anxiety symptoms and quality of life in these patients was tested using linear regression, controlling for confounding variables. A total of 205 patients were invited to participate and 133 (64.8%) agreed to fill out the questionnaire. On the adjusted model, reading religious literature was found to be inversely associated with depressive symptoms (P < 0.001). In addition, the psychological domain of quality of life was positively associated with an increase in patient religiosity (P = 0.030) and greater religious importance for recovery from their dialysis condition (P = 0.016), whereas the environmental domain was positively associated with greater religious importance for recovery (P = 0.032). No religious aspects were associated with anxiety symptoms. Religiousness is associated with less depressive symptoms and better quality of life in Brazilian dialysis patients. Nephrologists should evaluate the patient's spirituality and religion in order to provide more integrative care.
22099481
Hydraulic performance of grass swales for managing highway runoff.
The hydraulic performance of grass swales as a highway stormwater control measure was evaluated in a field-scale study adjacent to a Maryland highway. mon swale design alternatives, pretreatment grass filter strips and vegetated check dams, pared during 52 storm events over 4.5 years. Swale performance is described via three regimes, dependent on the relative size of the rainfall event. Overall, half of the events were small enough that the entire flow was stored, infiltrated, and evapotranspirated by the swales, resulting in no net swale discharge. Swales significantly reduced total volume and flow magnitudes generally during events with rainfall less than 3 cm. While the majority of improvement can be attributed to the swales, inclusion of check dams increases swale effectiveness. Pretreatment grass filter strips produced mixed effects. The swales demonstrated essentially no volumetric reduction during large storm events, functioning instead as conveyance, and smoothing fluctuations in flow.
22099480
Prometheus's heart: what lies beneath.
A heart attack kills off many cells in the heart. Parts of the heart e thin and fail to contract properly following the replacement of lost cells by scar tissue. However, the notion that the same adult cardiomyocytes beat throughout the lifespan of the organ and organism, without the need for a minimum turnover, gives way to a fascinating investigations. Since the late 1800s, scientists and cardiologists wanted to demonstrate that the cardiomyocytes cannot be generated after the perinatal period in human beings. This curiosity has been passed down in subsequent years and has motivated more and more accurate studies in an attempt to exclude the presence of renewed cardiomyocytes in the tissue bordering the ischaemic area, and then to confirm the dogma of the heart as terminally differentiated organ. Conversely, peri-lesional mitosis of cardiomyocytes were discovered initially by light microscopy and subsequently confirmed by more sophisticated technologies. Controversial evidence of mechanisms underlying myocardial regeneration has shown that adult cardiomyocytes are renewed through a slow turnover, even in the absence of damage. This turnover is ensured by the activation of rare clusters of progenitor cells interspersed among the cardiac cells functionally mature. Cardiac progenitor cells continuously interact with each other, with the cells circulating in the vessels of the coronary microcirculation and myocardial cells in auto-/paracrine manner. Much remains to be understood; however, the limited functional recovery in human beings after myocardial injury clearly demonstrates weak regenerative potential of cardiomyocytes and encourages the development of new approaches to stimulate this process.
22099484
Strategies for reducing radiation exposure in multi-detector row CT.
Many tools and strategies exist to enable the reduction of radiation exposure puted tomography (CT). mon CT metrics of x-ray output, CTDI(vol) and DLP, are explained and serve as the basis for monitoring radiation exposure from CT scans. Many strategies to dose optimize CT protocols are explored that, bination with available hardware and software tools, allow robust diagnostic quality CT scans to be performed with a radiation exposure appropriate for the clinical scenario and the size of the patients. Specific emergency department example protocols are used to demonstrate these techniques.
22099485
Updated imaging of traumatic brain injury.
Computed tomography (CT) and magnetic resonance (MR) play important roles in the evaluation of traumatic brain injury. Modern CT scanners allow for rapid and accurate diagnosis of intracranial hemorrhage and mass effect and allow the efficient implementation of emergent CT angiography. Newer sequences, such as gradient recalled echo, susceptibility-weighted imaging, and diffusion-weighted imaging, can provide greater sensitivity for specific types of diffuse posttraumatic brain injury. MR spectroscopy can provide additional chemical information, and diffusion tensor imaging can provide information about white matter injury. Patient treatment can be optimized using the diagnostic and prognostic information derived from current imaging techniques.
22099486
The imaging of maxillofacial trauma and its pertinence to surgical intervention.
Maxillofacial skeletal injuries account for a large proportion of emergency department visits and often result in surgical consultation. Although many of the principles of detection and repair are basic, the evolution of technology and therapeutic strategies has led to improved patient es. This article aims to provide a review of the imaging aspects involved in maxillofacial trauma and to delineate its relevance to management.
22099487
Multi-detector row CT angiography of the neck in blunt trauma.
Blunt cerebrovascular injury (BCVI) is mon but potentially catastrophic; 80% are caused by vehicle collisions. Ischemic events secondary to untreated BCVI mon, with high injury-specific mortality. This has led to implementation of screening programs based on mechanism of injury, clinical presentation, and injury patterns identified on puted tomography (CT) imaging. The standard of reference for diagnosis is four-vessel digital subtraction angiography. Given its availably in trauma service institutions, use of multidetector CT angiography has increased. This article presents the evidence and the controversies surrounding its use. Available protocols, injury description, and grading, as well as potential pitfalls are reviewed.
22099488
Imaging of acute head and neck infections.
Tonsillar infection is the mon cause of infections of the neck in children and young adults whereas odontogenic infection is the mon cause in older population groups. Other sources of neck infection include the salivary glands, nasal sinuses, middle ear and mastoids, cervical lymph nodes, and trauma. Computed tomography and magnetic resonance imaging have excellent sensitivity for the recognition of deep infections, particularly for the identification of abscess formation and its precise location and extension of disease. A careful assessment of potential plications, such as promise, osteomyelitis, and airway narrowing, should be performed routinely.
22099489
Imaging of aortic and branch vessel trauma.
Although infrequently encountered in busy trauma centers, injuries to the aorta and branch vessels remain an important cause of trauma-related mortality. Advances in the diagnosis and management of these injuries have led to more accurate and timely imaging, and improved patient es. Despite these advances, several challenges in evaluating the severely injured trauma patient remain. This review provides an overview of current concepts in the imaging of aortic and branch vessel injuries, and provides pointers to improve detection and interpretation of more challenging injuries.
22099490
Splenic trauma: what is new?
Evaluation for splenic injury is an ponent of patient assessment after blunt abdominal trauma. Key imaging modalities include ultrasound, particularly for rapid identification of hemoperitoneum, puted tomography (CT), which permits a more detailed and accurate determination of splenic integrity. Specific findings at contrast-enhanced multidetector CT (MDCT) should prompt the consideration of catheter angiography with arterial embolization as an adjunct to nonsurgical management. This article reviews the roles of imaging in the management of splenic trauma, illustrates the MDCT appearance of various splenic injuries, and discusses imaging-based indications for operative and angiographic intervention.
22099492
Multi-detector row CT of acute non-traumatic abdominal pain: contrast and protocol considerations.
This article discusses the critical protocol considerations in imaging patients with abdominal pain in the emergency department, specifically, the use of oral contrast, intravenous contrast, image postprocessing, and radiation dose. These considerations related to the use puted tomography imaging of abdominal pain are reviewed in an evidence-based fashion.
22099491
CT imaging of blunt traumatic bowel and mesenteric injuries.
Delayed diagnosis of a bowel or mesenteric injury resulting in hollow viscus perforation leads to significant morbidity and mortality from hemorrhage, peritonitis, or abdominal sepsis. The timely diagnosis of bowel and mesenteric injuries requiring operative repair depends almost exclusively on their early detection by the radiologist puted tomography examination, because the clinical signs and symptoms of these injuries are not specific and usually develop late. Therefore, the radiologist must be familiar with the often-subtle imaging findings of bowel and mesenteric injury that will allow for appropriate triage of a patient who has sustained blunt trauma to the abdomen or pelvis.
22099493
Imaging of abdominal pain in pregnancy.
This article reviews the evolving radiology and clinical literature on imaging of mon and mon maternal nonobstetric conditions of the abdomen and pelvis, including appendicitis, urolithiasis, and biliary disease, as well as on trauma to the maternal abdomen and pelvis and to the fetus. mendations for imaging these conditions, based on the literature to date and on the authors' experiences at two tertiary-care institutions with busy obstetric services, are proposed. The potential and theoretical fetal and maternal risks from such imaging are also reviewed.
22099494
Diagnosis of acute gastrointestinal hemorrhage and acute mesenteric ischemia in the era of multi-detector row CT.
Gastrointestinal hemorrhage and mesenteric ischemia are two conditions that require rapid and accurate diagnosis. In this article, the author discusses these conditions in the light of current available diagnosing modalities, such as puted tomography.
22099496
Detrimental effect of apoptosis of lymphocytes at an early time point of experimental abdominal sepsis.
Apoptosis of lymphocytes is considered a late sequelum in the sepsis cascade. The role of apoptosis of lymphocytes as a driver of final e was investigated.
22099497
Activity in vitro of hydrogen peroxide vapour against Clostridium difficile spores.
Clostridium difficile spores are shed in high numbers by infected patients and are resistant to desiccation and some disinfectants. We explored the in vitro activity of hydrogen peroxide vapour (HPV) against several strains of C. difficile spores using a spore-carrier test. Spores were dried on polyvinyl chloride or laminate carriers at mean concentrations of 4.7-6.9 log(10) spores/carrier, which were then decontaminated using HPV. C. difficile pletely eradicated from the exposed carriers regardless of the C. difficile strain or surface used. HPV can be considered for the eradication of C. difficile spores from the hospital environment.
22099498
Nosocomial outbreak of Myroides odoratimimus urinary tract infection in a Tunisian hospital.
We report a ial outbreak of urinary tract infection caused by Myroides odoratimimus, previously called Flavobacterium odoratum, in the urology unit of a Tunisian hospital. From May to November 2010, seven isolates of M. odoratimimus were recovered from urine. Pulsed-field gel electrophoresis clearly differentiated these isolates into two possibly related clones from two different periods. All patients but one had urinary calculi and underwent endourological surgery. All Myroides isolates were resistant to all antibiotics tested. Three patients were successfully treated with ciprofloxacin and rifampicin. Clinicians should be aware that M. odoratimimus may induce serious and prolonged ial outbreaks of urinary tract infections.
22099501
Primary hepatic carcinoid tumor.
Primary hepatic carcinoid tumor is rare and poses a challenge for diagnosis and management. We presented a case of primary hepatic carcinoid tumor in a 53-year-old female with plaint of right upper abdominal pain. Computer tomography scans revealed a hypervascular mass in segment 4 of the liver. An ultrasonography-guided biopsy showed a carcinoid tumor. No other lesions were found by the radiological investigations. Surgery resection was performed and histopathological examination revealed a primary hepatic carcinoid tumor. Three years later, recurrence was found and transcatheter arterial chemoembolization was performed. After transcatheter arterial chemoembolization, the patient has been free of symptom and had no radiological disease progression for over 6 months. Surgical bination with transcatheter arterial chemoembolization is effective to offer excellent palliation.
22099500
Family history of non-hematologic cancers among Waldenstrom macroglobulinemia patients: a preliminary study.
Little is known about the epidemiology and etiology of Waldenstrom macroglobulinemia (WM). Despite several studies of the relation between family history and B-cell disorders and WM, family history of non-hematologic cancers has not been systematically investigated. We thus examined associations of family history of breast, colorectal, lung, ovarian, and prostate cancers with WM.
22099502
Tularemia in Alaska, 1938 - 2010.
Tularemia is a serious, potentially life threatening zoonotic disease. The causative agent, Francisella tularensis, is ubiquitous in the Northern hemisphere, including Alaska, where it was first isolated from a rabbit tick (Haemophysalis leporis-palustris) in 1938. Since then, F. tularensis has been isolated from wildlife and humans throughout the state. Serologic surveys have found measurable antibodies with prevalence ranging from < 1% to 50% and 4% to 18% for selected populations of wildlife species and humans, respectively. We reviewed and summarized known literature on tularemia surveillance in Alaska and summarized the epidemiological information on human cases reported to public health officials. Additionally, available F. tularensis isolates from Alaska were analyzed using canonical SNPs and a multi-locus variable-number tandem repeats (VNTR) analysis (MLVA) system. The results show that both F. t. tularensis and F. t. holarctica are present in Alaska and that subtype A.I, the most virulent type, is responsible for most recently reported human clinical cases in the state.
22099504
Diuretics and salt transport along the nephron.
The clinical use of diuretics almost uniformly predated the localization of their site of action. The consequence of diuretic specificity predicts clinical application and side effect, and the proximity of the sodium transporters, one to the next, often dictates potency or diuretic efficiency. All diuretics function by inhibiting the normal transport of sodium from the filtrate into the renal tubular cells. This movement of sodium into the renal epithelial cells on the apical side is facilitated by a series of transporters whose function is, in turn, dependent on the adenosine triphosphate (ATP)-dependent Na-K cotransporter on the basolateral side of the cell. Our growing understanding of the physiology of sodium transport has spawned new possibilities for diuretic development.
22099505
Update in diuretic therapy: clinical pharmacology.
All diuretics except spironolactone exert their effects from the lumen of the nephron. Thus, to exert an effect, they must reach the urine. Pharmacokinetics (PK) describes this access. Different edematous disorders can affect access to this site of action and therein affect response to a diuretic. In addition, once a diuretic reaches the site of action, a response ensues. The characteristics of this response that can be affected by a patient's clinical condition are described by the pharmacodynamics (PD) of a diuretic. To understand the mechanisms of abnormal response to a diuretic one must dissect its PK and PD in different edematous disorders. For example, in patients with renal insufficiency, the mechanism of poor diuretic response is PK. In contrast, in patients with cirrhosis or in those with congestive heart failure, it is PD. In patients with nephrotic syndrome, both PK and PD are operative. These different mechanisms mandate differences in therapeutic strategy, as explained in this article.
22099506
Diuretics in the treatment of hypertension.
Diuretics are powerful agents that impair sodium reabsorption in renal tubules. Their ability to alter long-term sodium balance induces important hemodynamic changes that result in a reduction in peripheral resistance and sustained reduction in blood pressure. A pharmacologically diverse group of drugs, they remain a mainstay in the therapy of hypertension. Clinical trials over the past 4 decades consistently have shown that blood pressure lowering obtained from a diuretic-based regimen reduces cardiovascular events. The ability of diuretics to augment the efficacy of nearly all other classes of antihypertensives makes them highly versatile and an important pharmacotherapeutic intervention to achieve blood pressure control. This article reviews key aspects of the use of diuretics relevant to the clinical management of hypertension.
22099507
Use of diuretics in heart failure and cirrhosis.
Sodium and water retention in cardiac failure and cirrhosis is pivotal in the morbidity and mortality of patients with these disorders. Moreover, the pathophysiology of these edematous disorders is quite similar. Both disorders have activation of the renin-angiotensin-aldosterone system, increased sympathetic activity, and nonosmotic stimulation of arginine vasopressin, which is initiated by unloading of the arterial baroreceptors; this occurs secondary to diminished cardiac output with heart failure and primary systemic arterial vasodilation with cirrhosis. With mon pathophysiology causing pulmonary congestion, ascites, and peripheral edema, diuretics are pivotal in the therapy of patients with heart failure and cirrhosis. Advanced cardiac failure and cirrhosis both show secondary hyperaldosteronism and impaired renal escape from the sodium-retaining effect of aldosterone. However, currently there are contradictory uses of mineralocorticoid-receptor antagonists in cardiac failure (non-natriuretic doses) versus cirrhosis (natriuretic doses). This disparity relates to the greater potential of hyperkalemia in cardiac failure patients receiving inhibitors of the renin-angiotensin-aldosterone system. This review discusses the beneficial and potentially deleterious effects of diuretic use in patients with cardiac failure and cirrhosis.
22099508
Intravenous high-dose furosemide and hypertonic saline solutions for refractory heart failure and ascites.
Several studies have shown the efficacy of hypertonic saline solution infusion in conditions in which regional organ blood flow is impaired. Our group has shown that treatment of patients with diuretic-resistant heart failure with high-dose furosemide plus hypertonic saline is effective and well tolerated, improving symptoms of congestion, reducing plasma levels of markers of neurohormonal and inflammatory activation, decreasing hospital readmission rates, and reducing long-term mortality. The same regimen was shown to be better than repeated paracentesis in patients with cirrhosis and refractory ascites, yielding better control of ascites, pleural effusions, and/or leg edema without an increase mon adverse effects linked to high-dose furosemide such as hepatic encephalopathy.
22099510
Diuretics and disorders of calcium homeostasis.
monly are administered in disorders of sodium balance. Loop diuretics inhibit the Na-K-2Cl transporter and also increase calcium excretion. They are often used in the treatment of hypercalcemia. Thiazide diuretics block the thiazide-sensitive NaCl transporter in the distal convoluted tubule, and can decrease calcium excretion. They are often used in the treatment of nephrolithiasis. Carbonic anhydrase inhibitors decrease bicarbonate absorption and the resultant metabolic acidosis can increase calcium excretion. Their use can promote nephrocalcinosis and nephrolithiasis. This review will address the use of diuretics on disorders of calcium homeostasis.
22099509
Diuretics in acute kidney injury.
Acute kidney injury (AKI) mon in hospitalized patients and is associated with significant morbidity and mortality. The incidence of AKI is increasing and despite clinical advances there has been little change in the es associated with AKI. A variety of interventions, including loop diuretics, have been tested for the prevention and treatment of AKI; however, none to date have shown convincing benefits in clinical studies, and the management of AKI remains largely supportive. In this article, we review the pharmacology and experimental and clinical evidence for loop diuretics in the management of AKI. In addition, we also review evidence for other agents with diuretic and/or natriuretic properties such as thiazide diuretics, mannitol, fenoldopam, and natriuretic peptides in both the prevention and treatment of AKI. Implications for current clinical practice are outlined to guide clinical decisions in this field.
22099511
Metabolic complications associated with use of diuretics.
Diuretics monly used therapeutic agents that act to inhibit sodium transport systems along the length of the renal tubule. The most effective diuretics are inhibitors of sodium chloride transport in the thick ascending limb of Henle. Loop diuretics mobilize large amounts of sodium chloride and water and produce a copious diuresis with a sharp reduction of extracellular fluid volume. As the site of action of diuretics moves downstream (thiazide and potassium-sparing diuretics), their effectiveness declines because the transport systems they inhibit have low transport capacity. Depending on the site of action diuretics can influence the renal handling of electrolyte-free water, calcium, potassium, protons, sodium bicarbonate, and uric acid. As a result, electrolyte and acid-base monly pany diuretic use. Glucose and lipid abnormalities also can occur, particularly with the use of thiazide diuretics. This review focuses on the plications associated with the use of diuretics. The development of plications can be minimized with careful monitoring, dosage adjustment, and replacement of electrolyte losses.
22099512
Diuretic-associated hyponatremia.
Soon after their introduction in 1957, thiazide diuretics became a recognized cause of hyponatremia. Thiazides may be the sole cause and they may exacerbate hyponatremia in patients with disorders that cause the syndrome of inappropriate antidiuretic hormone secretion. Although thiazides do not inhibit the ability to concentrate the urine, they impair diluting ability in several ways: inhibition of sodium and chloride transport at cortical diluting sites; stimulation of vasopressin release; reduction of glomerular filtration and enhanced proximal water reabsorption, which reduce delivery to the distal diluting sites; and, possibly, a direct effect on water flow in the collecting duct. Water retention caused by impaired water bined with cation depletion may result in severe hyponatremia. Thiazides should be avoided in frail elderly patients with chronically high water intake or in others who depend on the excretion of maximally dilute urine to maintain fluid balance, such as patients with psychogenic polydipsia or heavy beer drinking. Inadvertent rapid correction of hyponatremia mon in thiazide-induced hyponatremia because the ability to dilute the urine is restored when the diuretic is discontinued and volume deficits are repaired. Hypokalemia, which often is present, increases the susceptibility to osmotic demyelination syndrome and replacement of potassium deficits contributes to the increase in serum sodium concentration.
22099513
Brittle leaf disease induces an oxidative stress and decreases the expression of manganese-related genes in date palm (Phoenix dactylifera L.).
In Tunisia, date orchards are being decimated by a disease called brittle leaf disease of unknown origin. Previous studies reported that affected soils, roots and leaves were manganese deficient. In this study, we investigated the biochemical and molecular response of MFC-affected date palms to the oxidative stress generated by manganese deficiency. Both the malondialdehyde (MDA) content which is indicative of lipid peroxidation and the activities of antioxidant enzyme were measured in affected leaves and roots. The expression profiles of oxidative stress-related genes encoding superoxide dismutases and peroxidases were also investigated. The data show that the MDA concentration increased but not significantly in affected leaves. However, such MDA increase was significant in roots of MFC-affected plants. The total superoxide dismutase (SOD) activity increased in affected leaves and roots, while RT-PCR experiments showed that MnSOD RNA decreased in affected leaves and roots unlike FeSOD and Cu/Zn-SOD RNA expression increased in these organs. In addition ascorbate peroxidase (APx) and glutathione peroxidase (GPx) RNA expression increased in diseased leaves and roots.
22099514
Acclimation to intense light implies changes at the level of trimeric subunits involved in the structural organization of the main light-harvesting complex of photosystem II (LHCII) and their isoforms.
When plants are grown under stable light conditions their photosynthetic apparatus undergoes a long-term acclimation process. Acclimation to different light intensities involves changes in the organization and/or abundance of plexes in the thylakoid membranes. In this study, spinach plants were exposed to differing light intensities, and the structural organization of the major light-harvesting chlorophyll plex of photosystem II (LHCII) was investigated by analysing their trimeric subunits. Plants were exposed to three different light intensities, 100 μmol quanta m⁻² s⁻¹, 200 μmol quanta m⁻² s⁻¹ and an elevated light intensity, 400 μmol quanta m⁻² s⁻¹, sufficient to provoke a moderate stress response in the form of down regulation of PSII. "MicroRotofor" analysis showed the presence of LHCII with different pIs and revealed a clear decline in their abundance as light intensity increased from 100 to 400 μmol quanta m⁻² s⁻¹. The three subunits (Lhcb1, Lhcb2, Lhcb3) behaved differently from each other as: Lhcb1 decreased more significantly than Lhcb2, whereas Lhcb3 was reduced only at a light window at which Lhcb1 and Lhcb2 abundance has already been depleted under intense irradiation. Interestingly, we also found that isoforms of Lhcb1 subunit (Lhcb1.1; 1.2; 1.3) behaved differently in response to elevated light intensity, suggesting an essential role of these isoforms to light adaption and consequently explaining the presence of this multigenic family, often identified among higher plants.
22099515
Developmental stage is an important factor that determines the antioxidant responses of young and old grapevine leaves under UV irradiation in a green-house.
The impact of UV irradiation was studied on photosynthesis, photosystem II photochemical yields and antioxidant responses using green-house grown grapevine (Vitis vinifera L. cv. Chardonnay) leaves. Supplemental UV irradiation (280-400 nm) was centred in the UV-B region, and corresponded to 8.95 kJ m⁻² d⁻¹ global (280-400 nm) or 8.04 kJ m⁻² d⁻¹ UV-B (280-315 nm) biologically effective dose. UV irradiation was applied daily and its effects were evaluated after 4-days. Younger (1-3 weeks-old) leaves (YL) and older (4-6 weeks-old) leaves (OL) were affected differently, UV irradiation decreased their photochemical yields to 78% and 56%, respectively. Unlike OL, YL responded by an increase in UV-B absorbing pigment, anthocyanin and total phenolics contents. UV irradiation increased total antioxidant capacities in YL but not in OL. YL were also different in their ability to increase specific hydroxyl radical and singlet oxygen neutralizing capacities in response to the supplemental UV irradiation, which is reported here for the first time. Our results suggest that the ability of maintaining photosynthesis under supplemental UV is not necessarily determined by base levels of antioxidants but rather by their inducibilities in response to the irradiation and emphasise the importance paring leaves of the same age in UV studies. Correlations between various antioxidant capacities, pigment contents and photosynthesis parameters were also examined. However, no single element of the defence system can be picked up as decisive factor of sensitivity to UV.
22099516
Potato cytosine methylation and gene expression changes induced by a beneficial bacterial endophyte, Burkholderia phytofirmans strain PsJN.
Burkholderia phytofirmans strain PsJN is a highly effective plant-beneficial endophyte. We have used bination of capillary electrophoresis and methylation-sensitive amplification length polymorphism (CE-MSAP) analysis to investigate the potato genomic DNA cytosine methylation changes that occur in response to PsJN bacterization. Six weeks after PsJN inoculation, over 6800 loci were identified and assessed in two in vitro grown potato varieties, the strongly-responsive Red Pontiac and the poorly-responsive Superior. Compared to non-bacterized control, bacterized Red Pontiac exhibited little change in the overall cytosine methylation, although methylation polymorphisms did occur. In contrast, poorly-responsive Superior exhibited significantly higher levels of overall cytosine methylation and a decrease in the number of non-methylated sites in the bacterized pared to controls. Superior had significantly higher DNA methylation and DNA hyper-methylation than Red Pontiac, suggesting that enhanced DNA loci methylation is involved in the suppression of PsJN-induced plant growth stimulation. Several DNA fragments, corresponding to different open reading frames exhibiting methylation polymorphisms in Red Pontiac or Superior were sequenced. Gene expression analysis of a subset of those genes was carried out using real time PCR. We identified several genes whose transcript levels were either enhanced or decreased in response to PsJN in a variety-specific way, as well as genes that were specifically enhanced in both varieties in response to the endophyte.
22099517
Generation of poly-β-hydroxybutyrate from externally provided acetate in rice root.
During the investigation of the metabolism of ¹⁴C-acetate or ¹⁴C-succinate in rice seedlings, an unknown organic acid (X) with a high specific radioactivity was detected in 10,000 × g 30 min precipitate-fraction of rice roots. The X was hardly extracted by 0.1 N-H₂SO₄ boiling, but was extracted by 0.5 N-KOH boiling. The X was co-chromatographed with several known organic acids, and the radioactive peak of the X matched β-hydroxybutyric acid (β-hydroxybutyrate). The radioactive X and β-hydroxybutyrate were then heated with concentrated H₂SO₄. The radioactivity and the titration value pletely converted to crotonic acid. Thus, it was concluded that the X was β-hydroxybutyrate, and the original form of this acid was presumed to be poly-β-hydroxybutyrate (PHB). Then rice root incubated with 2-¹⁴C-acetate was extracted with hot-ethanol, ethanol/ether, and hot-chloroform. Approximately 10% of the radioactivity absorbed was detected in the chloroform fraction. The chloroform fraction was co-precipitated with authentic PHB by the addition of acetone/ether, and almost all the radioactivity was co-precipitated with the PHB. The radioactive co-precipitate was then heated with 0.5 N-NaOH, and chromatographed. The radioactivity of β-hydroxybutyrate plus crotonic acid almost matched that of the co-precipitate before alkaline-hydrolysis. Hence the radioactive co-precipitate was confirmed to be PHB. In wheat and radish seedlings, 2-¹⁴C-acetate was also assimilated into PHB. It is concluded that externally provided acetate was rapidly converted to PHB in higher plants.
22099518
Identification of water stress genes in Pinus pinaster Ait. by controlled progressive stress and suppression-subtractive hybridization.
Climate change is a major challenge particularly for forest tree species, which will have to face the severe alterations of environmental conditions with their current genetic pool. Thus, an understanding of their adaptive responses is of the utmost interest. In this work we have selected Pinus pinaster as a model species. This pine is one of the most important conifers (for which molecular tools and knowledge are far more scarce than for angiosperms) in the Mediterranean Basin, which is characterised in all foreseen scenarios as one of the regions most drastically affected by climate change, mainly because of increasing temperature and, particularly, by increasing drought. We have induced a controlled, increasing water stress by adding PEG to a hydroponic culture. We have generated a subtractive library, with the aim of identifying the genes induced by this stress and have searched for the most reliable expressional candidate genes, based on their overexpression during water stress, as revealed by microarray analysis and confirmed by RT-PCR. We have selected a set of 67 candidate genes belonging to different functional groups that will be useful molecular tools for further studies on drought stress responses, adaptation, and population genomics in conifers, as well as in breeding programs.
22099519
Identification of genes up-regulated during somatic embryogenesis of cucumber.
Somatic embryogenesis is a method of plant regeneration, but it can also be used as a model to study plant development. A normalized library of cDNA fragments representing genes up-regulated after the induction of somatic embryogenesis in cucumber suspension cultures was constructed using the suppression subtractive hybridization technique. Candidate cDNA fragments (119) were classified according to their similarity to genes encoding known proteins and the presence of potential functional domains. Of the translation products with homology to known proteins, about 23% were possibly involved in metabolism, 13% represented proteins with a probable role in munication and signal transduction, about 12% were likely to participate in protein synthesis, while around 10% were potential transcription factors. The genes corresponding to four of the cDNAs were subsequently analyzed in more detail: CsSEF2, CsSEM1 and CsSESTK1 encoding putative transcription factors or co-activators, and CsSECAD1 encoding cinnamyl alcohol dehydrogenase. Full-length cDNAs were isolated and analyzed. RT-PCR confirmed the up-regulation of these genes after the induction of somatic embryogenesis and showed the presence of their transcripts in other tissues. The in situ localization of transcripts of the CsSEF2 and CsSEM1 genes demonstrated that signalling in somatic embryo tissues involving these factors is concentrated in the cotyledon primordia and roots.
22099520
Sexual functioning in chronic kidney disease: the association with depression and anxiety.
Sexual functioning posed of both physiological and psychological factors among patients with chronic kidney disease (CKD). However, the role of depression and anxiety has not yet been studied extensively. This study aimed to investigate the relation of depressive and anxiety symptoms to sexual functioning among hemodialysis (HD) and peritoneal dialysis patients. A sample of 144 patients was recruited from three general hospitals in the broader area of Athens, consisting of 84 patients undergoing in-center HD and 60 patients in continuous ambulatory peritoneal dialysis. Measurements were conducted with the following instruments: the World Health Organization Quality of Life instrument, the General Health Questionnaire (GHQ-28), the State-Trait Anxiety Inventory (STAI 1/STAI 2), and the Center for Epidemiologic Studies Depression Scale. The results indicated that satisfaction about sexual life had negative association with all the subscales of GHQ-28 questionnaire (somatic symptoms, anxiety/insomnia, social dysfunction, severe depression). Sexual functioning was also related negatively to depression as well as state and trait anxieties. Findings provide evidence that the presence of depressive and anxiety symptoms relates significantly to the negative evaluation of sexual functioning in patients with CKD.