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22099268

Sperm retrieval techniques for assisted reproduction.

Different surgical methods such as PESA, MESA, TESA, TESE and micro-TESE have been developed to retrieve spermatozoa from either the epididymis or the testis according to the type of azoospermia, i.e., obstructive or non-obstructive. Laboratory techniques are used to remove contaminants, cellular debris, and red blood cells following collection of the epididymal fluid or testicular tissue. Surgically-retrieved spermatozoa may be used for intracytoplasmic sperm injection (ICSI) and/or cryopreservation. In this article, we review the surgical procedures for retrieving spermatozoa from both the epididymis and the testicle and provide technical details of monly used methods. A critical analysis of the advantages and limitations of the current surgical methods to retrieve sperm from males with obstructive and non-obstructive azoospermia is presented along with an overview of the laboratory techniques routinely used to process surgically-retrieved sperm. Lastly, we summarize the results from the current literature of sperm retrieval, as well as the clinical e of ICSI in the clinical scenario of obstructive and nonobstructive azoospermia.

22099269

Significant heterogeneity in terms of diagnosis and treatment of renal cell carcinoma at a private and public hospital in Brazil.

A great number of small renal lesions have now been detected. Nowadays, partial nephrectomy has more frequently been adopted for surgical treatment of earlier stage disease. Previous studies have associated patient, institutional, and health care system factors with surgery type. The aim of this study was pare the diagnosis and treatment of renal cell carcinoma (RCC) according to hospital type, public versus private, in our country.

22099270

Age-related testosterone decline in a Brazilian cohort of healthy military men.

Androgen decline in the aging man has e a topic of increasing clinical relevance worldwide, as the reduction in testosterone levels has been reported to be panied by loss of muscle mass, accumulation of central adiposity, impaired mobility and increase risk of bone fractures. Although well-established in studies conducted in developed countries, progressive decline in serum testosterone levels with age has been poorly investigated in Brazil.

22099272

Bladder exstrophy: reconstructed female patients achieving normal pregnancy and delivering normal babies.

Bladder exstrophy (BE) is an anterior midline defect that causes a series of genitourinary and muscular malformations, which demands surgical intervention for correction. Women with BE are fertile and able to have children without this disease. The purpose of this study is to assess the sexual function and quality of life of women treated for BE.

22099273

Alkaline citrate reduces stone recurrence and regrowth after shockwave lithotripsy and percutaneous nephrolithotomy.

To evaluate the preventive effects of alkaline citrate on stone recurrence as well as stone growth post-ESWL or PCNL in patients with calcium-containing stones.

22099271

Prostatic carcinomas with neuroendocrine differentiation diagnosed in needle biopsies, a morphologic study of 7 cases among 465 sequential biopsies in a tertiary cancer center.

Neuroendocrine carcinomas (NEC) of the prostate are rare, with only a few series hitherto reported. The objective of this study was to assess in a single institution the clinical and morphologic characteristics of neuroendocrine carcinomas diagnosed in needle core biopsies.

22099274

Inflammation and endothelial activation in benign prostatic hyperplasia and prostate cancer.

Emerging insights underline a link among chronic inflammation and endothelial activation with benign prostatic hyperplasia (BPH) and prostate cancer (PCa). We aim to investigate whether specific plasma markers of inflammation and endothelial activation allow to discriminate BPH and PCa.

22099266

Comparative study between trimetazidine and ice slush hypothermia in protection against renal ischemia/reperfusion injury in a porcine model.

The aim of the study was pare the effects of renal ice slush hypothermia and the use of trimetazidine in the protection against ischemia/reperfusion (I/R) injury.

22099298

Staying alive: defensive strategies in the BCL-2 family playbook.

Much debate surrounds how prosurvival members of the BCL-2 family repress opening of the BAX/BAK channel to block apoptosis; in this issue Llambi et al. (2011) identify two modes of apoptosis inhibition that exhibit surprisingly different behavior upon repeat proapoptotic challenges by BH3-only proteins.

22099275

Vasectomy occlusion technique combining thermal cautery and fascial interposition.

Recent research on vasectomy shows bining cautery and fascial interposition (FI) achieves the most effective occlusion of the vas and minimizes the risk of failure. We present a technique bines cautery and FI and is suitable for low-resource settings.

22099276

Percutaneous intervention of large bladder calculi in neuropathic voiding dysfunction.

To report our results and rationale for treating large bladder calculi in patients with neuropathic voiding dysfunction (NVD) using percutaneous cystolithalopaxy.

22099299

A20: more than one way to skin a cat.

In this issue of Molecular Cell, Skaug et al. (2011) propose a polyubiquitin-dependent, noncatalytic mechanism by which the deubiquitinase A20 inhibits IκB kinase and NF-κB activation.

22099277

Botulinum toxin A for the treatment of neurogenic detrusor overactivity in multiple sclerosis patients.

Neurogenic detrusor overactivity (NDO) mon in patients who suffer from multiple sclerosis (MS). When the usual pharmacological treatment fails, botulinum toxin type A (BTX-A) injections can be proposed. The safety and efficacy of this treatment are already well known, but only a few studies focus on its use in patients with MS.

22099300

Mitosis hit with an ATM transaction fee: aurora B-mediated activation of ATM during mitosis.

In this issue of Molecular Cell, Yang et al. (2011) demonstrate that Aurora B phosphorylates ATM, leading to its mitotic activation and ability to phosphorylate Bub1 and regulate the spindle checkpoint, thus maintaining genomic integrity.

22099301

PGC1α confers specificity-metabolic stress and p53-dependent transcription.

In this issue of Molecular Cell, Sen et al. (2011) report the involvement of PGC1α in modulating the transcriptional activity of p53 in metabolically challenged cells. They provide important insights into the mechanisms linking length and strength of the metabolic stress stimuli to the specific activation of p53 target genes.

22099292

The one-stop clinic as the standard of out-patient care in a hospital urology department.

To evaluate the performance of a 'one-stop' clinic in terms of proportion of discharges or inclusion in surgical waiting lists.

22099302

Fine-tuning of Drp1/Fis1 availability by AKAP121/Siah2 regulates mitochondrial adaptation to hypoxia.

Defining the mechanisms underlying the control of mitochondrial fusion and fission is critical to understanding cellular adaptation to diverse physiological conditions. Here we demonstrate that hypoxia induces fission of mitochondrial membranes, dependent on availability of the mitochondrial scaffolding protein AKAP121. AKAP121 controls mitochondria dynamics through PKA-dependent inhibitory phosphorylation of Drp1 and PKA-independent inhibition of Drp1-Fis1 interaction. Reduced availability of AKAP121 by the ubiquitin ligase Siah2 relieves Drp1 inhibition by PKA and increases its interaction with Fis1, resulting in mitochondrial fission. High AKAP121 levels, seen in cells lacking Siah2, attenuate fission and reduce apoptosis of cardiomyocytes under simulated ischemia. Infarct size and degree of cell death were reduced in Siah2(-/-) mice subjected to myocardial infarction. Inhibition of Siah2 or Drp1 in hatching C. elegans reduces their life span. Through modulating plex availability, our studies identify Siah2 as a key regulator of hypoxia-induced mitochondrial fission and its physiological significance in ischemic injury and nematode life span.

22099303

Peroxiredoxin II is an essential antioxidant enzyme that prevents the oxidative inactivation of VEGF receptor-2 in vascular endothelial cells.

Cellular antioxidant enzymes play crucial roles in aerobic organisms by eliminating detrimental oxidants and maintaining the intracellular redox homeostasis. Therefore, the function of antioxidant enzymes is inextricably linked to the redox-dependent activities of multiple proteins and signaling pathways. Here, we report that the VEGFR2 RTK has an oxidation-sensitive cysteine residue whose reduced state is preserved specifically by peroxiredoxin II (PrxII) in vascular endothelial cells. In the absence of PrxII, the cellular H(2)O(2) level is markedly increased and the VEGFR2 es inactive, no longer responding to VEGF stimulation. Such VEGFR2 inactivation is due to the formation of intramolecular disulfide linkage between Cys1199 and Cys1206 in the C-terminal tail. Interestingly, the PrxII-mediated VEGFR2 protection is achieved by association of two proteins in the caveolae. Furthermore, PrxII deficiency suppresses tumor angiogenesis in vivo. This study thus demonstrates a physiological function of PrxII as the residential antioxidant safeguard specific to the redox-sensitive VEGFR2.

22099304

Direct, noncatalytic mechanism of IKK inhibition by A20.

A20 is a potent anti-inflammatory protein that inhibits NF-κB, and A20 dysfunction is associated with autoimmunity and B cell lymphoma. A20 harbors a deubiquitination enzyme domain and can employ multiple mechanisms to antagonize ubiquitination upstream of NEMO, a regulatory subunit of the IκB plex (IKK). However, direct evidence of IKK inhibition by A20 is lacking, and the inhibitory mechanism remains poorly understood. Here we show that A20 can directly impair IKK activation without deubiquitination or impairment of ubiquitination enzymes. We find that polyubiquitin binding by A20, which is largely dependent on A20's seventh zinc-finger motif (ZnF7), induces specific binding to NEMO. Remarkably, this ubiquitin-induced recruitment of A20 to NEMO is sufficient to block IKK phosphorylation by its upstream kinase TAK1. Our results suggest a noncatalytic mechanism of IKK inhibition by A20 and a means by which polyubiquitin chains can specify a signaling e.

22099306

RAM/Fam103a1 is required for mRNA cap methylation.

The 7-methylguanosine cap added to the 5' end of mRNA is required for efficient gene expression in eukaryotes. In mammals, methylation of the guanosine cap is catalyzed by RNMT (RNA guanine-7 methyltransferase), an enzyme previously thought to function as a monomer. We have identified an ponent of the mammalian cap methyltransferase, RAM (RNMT-Activating Mini protein)/Fam103a1, a previously uncharacterized protein. RAM consists of an N-terminal RNMT-activating domain and a C-terminal RNA-binding domain. As monomers RNMT and RAM have a relatively weak affinity for RNA; however, together their RNA affinity is significantly increased. RAM is required for efficient cap methylation in vitro and in vivo, and is indirectly required to maintain mRNA expression levels, for mRNA translation and for cell viability. Our findings demonstrate that RAM is an ponent of the core gene expression machinery.

22099307

Aurora-B mediated ATM serine 1403 phosphorylation is required for mitotic ATM activation and the spindle checkpoint.

The ATM kinase plays a critical role in the maintenance of genetic stability. ATM is activated in response to DNA damage and is essential for cell-cycle checkpoints. Here, we report that ATM is activated in mitosis in the absence of DNA damage. We demonstrate that mitotic ATM activation is dependent on the Aurora-B kinase and that Aurora-B phosphorylates ATM on serine 1403. This phosphorylation event is required for mitotic ATM activation. Further, we show that loss of ATM function results in shortened mitotic timing and a defective spindle checkpoint, and that abrogation of ATM Ser1403 phosphorylation leads to this spindle checkpoint defect. We also demonstrate that mitotically activated ATM phosphorylates Bub1, a critical kinetochore protein, on Ser314. ATM-mediated Bub1 Ser314 phosphorylation is required for Bub1 activity and is essential for the activation of the spindle checkpoint. Collectively, our data highlight mechanisms of a critical function of ATM in mitosis.

22099305

Heterotypic piRNA Ping-Pong requires qin, a protein with both E3 ligase and Tudor domains.

piRNAs guide PIWI proteins to silence transposons in animal germ cells. Reciprocal cycles of piRNA-directed RNA cleavage--catalyzed by the PIWI proteins Aubergine (Aub) and Argonaute3 (Ago3) in Drosophila melanogaster--expand the population of antisense piRNAs in response to transposon expression, a process called the Ping-Pong cycle. Heterotypic Ping-Pong between Aub and Ago3 ensures that antisense piRNAs predominate. We show that qin, a piRNA pathway gene whose protein product contains both E3 ligase and Tudor domains, colocalizes with Aub and Ago3 in nuage, a perinuclear structure implicated in transposon silencing. In qin mutants, less Ago3 binds Aub, futile Aub:Aub homotypic Ping-Pong prevails, antisense piRNAs decrease, many families of mobile genetic elements are reactivated, and DNA damage accumulates in nurse cells and oocytes. We propose that Qin enforces heterotypic Ping-Pong between Aub and Ago3, ensuring that transposons are silenced and maintaining the integrity of the germline genome.

22099308

NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming.

The histone lysine methyltransferase NSD2 (MMSET/WHSC1) is implicated in diverse diseases monly overexpressed in multiple myeloma due to a recurrent t(4;14) chromosomal translocation. However, the precise catalytic activity of NSD2 is obscure, preventing progress in understanding how this enzyme influences chromatin biology and myeloma pathogenesis. Here, we show that dimethylation of histone H3 at lysine 36 (H3K36me2) is the principal chromatin-regulatory activity of NSD2. Catalysis of H3K36me2 by NSD2 is sufficient for gene activation. In t(4;14)-positive myeloma cells, the normal genome-wide and gene-specific distribution of H3K36me2 is obliterated, creating a chromatin landscape that selects for a transcription profile favorable for myelomagenesis. Catalytically active NSD2 confers xenograft tumor formation upon t(4;14)-negative cells and promotes oncogenic transformation of primary cells in an H3K36me2-dependent manner. Together, our findings establish H3K36me2 as the primary product generated by NSD2 and demonstrate that genomic disorganization of this canonical chromatin mark by NSD2 initiates oncogenic programming.

22099309

PGC-1α, a key modulator of p53, promotes cell survival upon metabolic stress.

Metabolic stress results in p53 activation, which can trigger cell-cycle arrest, ROS clearance, or apoptosis. However, what determines the p53-mediated cell fate decision upon metabolic stress is not very well understood. We show here that PGC-1α binds to p53 and modulates its transactivation function, resulting in preferential transactivation of proarrest and metabolic target genes. Thus glucose starvation results in p53-dependent cell-cycle arrest and ROS clearance, but abrogation of PGC-1α expression results in extensive apoptosis. Additionally, prolonged starvation results in PGC-1α degradation itant with induction of apoptosis. We have also identified RNF2, a b group (PcG) protein, as the cognate E3 ubiquitin ligase. Starvation of mice where PGC-1α expression is abrogated results in loss of p53-mediated ROS clearance, enhanced p53-dependent apoptosis, and consequent severe liver atrophy. These findings provide key insights into the role of PGC-1α in regulating p53-mediated cell fate decisions in response to metabolic stress.

22099310

Applied force provides insight into transcriptional pausing and its modulation by transcription factor NusA.

Transcriptional pausing by RNA polymerase (RNAP) plays an essential role in gene regulation. Pausing is modified by various elongation factors, including prokaryotic NusA, but the mechanisms underlying pausing and NusA function remain unclear. Alternative models for pausing invoke blockade events that precede translocation (on-pathway), enzyme backtracking (off-pathway), or isomerization to a nonbacktracked, elemental pause state (off-pathway). We employed an optical trapping assay to probe the motions of individual RNAP molecules transcribing a DNA template carrying tandem repeats encoding the his pause, subjecting these enzymes to controlled forces. NusA significantly decreased the pause-free elongation rate of RNAP while increasing the probability of entry into short- and long-lifetime pauses, in a manner equivalent to exerting a ~19 pN force opposing transcription. The effects of force and NusA on pause probabilities and lifetimes support a reaction scheme where nonbacktracked, elemental pauses branch off the elongation pathway from the pretranslocated state of RNAP.

22099311

Telomere protection by TPP1/POT1 requires tethering to TIN2.

To prevent ATR activation, telomeres deploy the single-stranded DNA binding activity of TPP1/POT1a. POT1a blocks the binding of RPA to telomeres, suggesting that ATR is repressed through RPA exclusion. parison of the DNA binding affinities and abundance of TPP1/POT1a and RPA indicates that TPP1/POT1a by itself is unlikely to exclude RPA. We therefore analyzed the central shelterin protein TIN2, which links TPP1/POT1a (and POT1b) to TRF1 and TRF2 on the double-stranded telomeric DNA. Upon TIN2 deletion, telomeres lost TPP1/POT1a, accumulated RPA, elicited an ATR signal, and showed all other phenotypes of POT1a/b deletion. TIN2 also affected the TRF2-dependent repression of ATM kinase signaling but not to TRF2-mediated inhibition of telomere fusions. Thus, while TIN2 has a minor contribution to the repression of ATM by TRF2, its major role is to stabilize TPP1/POT1a on the ss telomeric DNA, thereby allowing effective exclusion of RPA and repression of ATR signaling.

22099313

A variant of the Ekman-Westborg and Julin trait.

Ekman-Westborg and Julin is a trait that shows multiple macrodontia and multituberculism affecting only the teeth with no other anomalies (E-WJ). The aim of this report is to present a case which appears to manifest all the clinical signs of the E-WJ trait including odontoma formation. A 18-year-old girl with gingival inflammation particularly in the maxillary insicor area was referred to the authors' department. Panoramic, periapical and cephalometric radiographs were examined plex odontoma associated with unerupted maxillary permanent lateral incisors was revealed. Intraoral examination revealed anterior crossbite, Angle Class III type malocclusion with mandibulary prominence and macrodontia of teeth 37, 12, 11 and 21. The patient was accepted as a new sporadic case of E-WJ. More case reports are needed to elucidate the causes and pathogenesis of this condition.

22099312

rRNA pseudouridylation defects affect ribosomal ligand binding and translational fidelity from yeast to human cells.

How pseudouridylation (Ψ), the mon and evolutionarily conserved modification of rRNA, regulates ribosome activity is poorly understood. Medically, Ψ is important because the rRNA Ψ synthase, DKC1, is mutated in X-linked dyskeratosis congenita (X-DC) and Hoyeraal-Hreidarsson (HH) syndrome. Here, we characterize ribosomes isolated from a yeast strain in which Cbf5p, the yeast homolog of DKC1, is catalytically impaired through a D95A mutation (cbf5-D95A). Ribosomes from cbf5-D95A cells display decreased affinities for tRNA binding to the A and P sites as well as the cricket paralysis virus internal ribosome entry site (IRES), which interacts with both the P and the E sites of the ribosome. This biochemical impairment in ribosome activity manifests as decreased translational fidelity and IRES-dependent translational initiation, which are also evident in mouse and human cells deficient for DKC1 activity. These findings uncover specific roles for Ψ modification in ribosome-ligand interactions that are conserved in yeast, mouse, and humans.

22099314

Maxillary sinus lift with solely autogenous bone compared to a combination of autogenous bone and growth factors or (solely) bone substitutes. A systematic review.

Literature regarding the e of maxillary sinus floor elevation to create sufficient bone fraction to enable implant placement was systematically reviewed. Bone fraction and implant survival rate were assessed to determine whether grafting material or applied growth factor affected bone fraction. Trials where sinus floor elevations with autogenous bone (controls) pared with autogenous bined with growth factors or bone substitutes, or solely with bone substitutes (test groups) were identified; 12 of 1124 fulfilled all inclusion criteria. paring the bone fraction after applying: autogenous bone; autologous bone with growth factors (platelet rich plasma); or autogenous bone and bone substitutes (bovine hydroxyapatite, bioactive glass, corticocancellous pig bone) revealed no significant differences in bone formation after 5 months. A significantly higher bone fraction was found in the autogenous bone pared to the sole use of β-tricalciumphosphate (P=0.036). The one-year overall implant survival rate showed no significant difference between implants. Bone bined with autogenous bone provide a reliable alternative for autogenous bone as sole grafting material to reconstruct maxillary sinus bony deficiencies, for supporting dental implants after 5 months. Adding growth factors (platelet rich plasma) to grafting material and the sole use of β-tricalciumphosphate did not promote bone formation.

22099315

Insulin promotes bone formation in augmented maxillary sinus in diabetic rabbits.

The role of insulin during the formation of bone in the augmented space of the maxillary sinus in patients with diabetes is unclear. The pared the differences in bone formation after maxillary sinus floor elevation in diabetic and healthy animals and evaluated the effects of insulin on osteogenesis and the differentiation and activities of the osteoblasts. 10 male Japanese white rabbits were divided into two groups after diabetic induction by a single injection of monohydrated alloxan and having maintained steady blood glucose levels. The groups included the diabetes mellitus group (DM; n=5) and the DM+insulin group (n=5); another five healthy prised the control group. Maxillary sinus floor elevation was performed by grafting hydroxyapatite particles. Compared with the control group, the newly formed bone area, number of blood vessels and osteoblasts, collagen I content and serum osteocalcin levels were significantly decreased in DM rabbits (P<0.01). Insulin treatment reversed the decrease in bone formation, blood vessels, osteoblasts, collagen I and serum osteocalcin (P<0.01). Insulin treatment also promoted osteogenesis in the augmented space of the diabetic rabbits, which might have resulted from promotion of osteoblast differentiation and upregulation of neovascularization.

22099316

Single stage repair of a complex pathology: end stage ischaemic cardiomyopathy, ascending aortic aneurysm and thoracic coarctation.

The not bination of ascending aortic pathology with late presenting coarctation is a difficult surgical challenge. The two stage approach is usually adopted. The necessity for cardiac transplantation adds to plexity: a trans-sternal approach and single stage repair e mandatory.

22099323

The Canadian Forces trauma care system.

According to the Trauma Association of Canada, a trauma system is a preplanned, organized and coordinated injury-control effort in a defined geographic area. An effective trauma system engages prehensive injury surveillance and prevention programs; delivers trauma care from the time of injury to recovery; engages in research, training and performance improvement; and establishes linkages with an all-hazards emergency preparedness program. To support bat mission in Afghanistan, the Canadian Forces (CF) developed prehensive trauma system based around its trauma hospital--the Role 3 Multinational Medical Unit (R3MMU) at Kandahar Airfield. This article reviews the ponents of a modern trauma system, outlines the evidence that trauma systems improve care to injury victims and describes how the current CF trauma system was developed.

22099324

Tactical combat casualty care in the Canadian Forces: lessons learned from the Afghan war.

Tactical Combat Casualty Care (TCCC) is intended to treat potentially preventable causes of death on the battlefield, but acknowledges that application of these treatments may place the provider and even the mission in jeopardy if performed at the wrong time. Therefore, TCCC classifies the tactical situation with respect to health care provision into 3 phases (care under fire, tactical field care and tactical evacuation) and only permits certain interventions to be performed in specific phases based on the danger to the provider and casualty. In the 6 years that the Canadian Forces (CF) have been involved in bat operations in Kandahar, Afghanistan, more than 1000 CF members have been injured and more than 150 have been killed. As a result, the CF gained substantial experience delivering TCCC to wounded soldiers on the battlefield. The purpose of this paper is to review the principles of TCCC and some of the lessons learned about battlefield trauma care during this conflict.

22099325

The Role 3 Multinational Medical Unit at Kandahar Airfield 2005-2010.

In late 2005, Canadian Forces Health Services (CFHS) was tasked with mand of the NATO Role 3 Multinational Medical Unit (R3MMU) on Kandahar Airfield in southern Afghanistan. Preparations drew on past experience and planning. plete hospital contingents were trained and deployed in rotation. Near-reality simulation training was undertaken with bat brigade, plete deployment of the field hospital in the exercise area. Standard operating procedures (SOP) were developed and applied by each rotation so successfully that they were adopted by the mand in late 2009. The Canadian period at R3MMU had the highest survival rate ever recorded for victims of war. Lessons learned are being applied among victims of the conflict and trauma. The experience of the R3MMU was used to successfully deploy a hospital as part of the earthquake relief effort in Haiti in 2010.The training protocols and SOP are being applied to disaster preparedness in Canadian civilian hospitals.

22099326

Utilization profile of the trauma intensive care unit at the Role 3 Multinational Medical Unit at Kandahar Airfield between May 1 and Oct. 15, 2009.

In the war against the Taliban, Canada was the lead North Atlantic Treaty Organization (NATO) nation to provide medical and surgical care to NATO soldiers, Afghanistan National Army soldiers, Afghanistan Nation Police, civilians working in and outside Kandahar Airfield and Afghanistan civilians at the Role 3 Multinational Medical Unit (R3MMU) from February 2006 to October 2009.

22099327

Physical rehabilitation following polytrauma. The Canadian Forces Physical Rehabilitation Program 2008-2011.

As a consequence of Canada's involvement in the war in Afghanistan, many members of the Canadian Forces have experienced debilitating injuries. Despite the Canadian Forces Health Services (CFHS) having outstanding relationships with many civilian care providers for the rehabilitation of injured soldiers, it became apparent early on that the high-level goals and aspirations of these returning soldiers were sometimes beyond the capability of these centres to facilitate. From this reality grew the need to develop a Physical Rehabilitation Program within the CFHS. This article describes the lessons learned since the creation of the program and outlines the future vision in terms of unique challenges and opportunities. The primary purpose of this article is to describe a hybrid model of civilian-military rehabilitation for injured soldiers and discuss the benefits and challenges of such a model of care.

22099328

Psychiatric lessons learned in Kandahar.

Not since the Korean War have the Canadian Forces engaged bat missions like those in Afghanistan. Combat, asymmetric warfare, violent insurgency and the constant threat of improvised explosive devices all contribute to the psychological stressors experienced by Canadian soldiers. Mental health teams deployed with the soldiers and provided assessment, treatment and education. Lessons learned included refuting the myth that all psychological disorders would be related to trauma; confirming that most patients do well after exposure to trauma; confirming that treating disorders in a war zone requires flexible and creative adaptation of civilian treatment guidelines; and confirming that in bat mission mental health practice is not limited to the clinical setting.

22099329

Left atrial volume predicts adverse cardiac and cerebrovascular events in patients with hypertrophic cardiomyopathy.

To prospectively evaluate the relationship between left atrial volume (LAV) and the risk of clinical events in patients with hypertrophic cardiomyopathy (HCM).

22099330

The new COSMIN guidelines confront traditional concepts of responsiveness.

The recently published "COSMIN" guidelines aim to rate properties of e instruments and state two issues with regard to responsiveness which is the instrument's ability to detect change over time. These issues parison of score changes with change of an external criterion using correlations and the judgement of traditional methods as inappropriate. The latter are the "transition" concept, a global rating of change, and parametric measures of responsiveness, for example, effect sizes. It can be shown that the methodology proposed by the guidelines has important weaknesses and that denunciation of traditional methods is not appropriate. Some claims of the guidelines about responsiveness do not match the demands of clinical reality and confront findings of numerous epidemiological studies.

22099331

The complex dialogue between (myo)fibroblasts and the extracellular matrix during skin repair processes and ageing.

The fibroblasts and the myofibroblasts are key players for maintaining skin homeostasis and for orchestrating physiological tissue repair. The (myo)fibroblasts are embedded in a sophisticated extracellular matrix (ECM) that they secrete, and plex and interactive dialogue exists between (myo)fibroblasts and their microenvironment. position of the ECM around (myo)fibroblasts is variable depending on the situation and, in addition to the secretion of the ECM, the (myo)fibroblasts, by secreting matrix metalloproteinases and tissue inhibitors of metalloproteinases can remodel this ECM. The (myo)fibroblasts and their microenvironment form a changing network with reciprocal actions leading to cell differentiation, proliferation, quiescence or apoptosis, and also acting on growth factor biodisponibility. In pathological situations (such as chronic wounds or excessive scarring), or during ageing, especially due to ultraviolet exposition, this dialogue between the (myo)fibroblasts and their microenvironment is disrupted, leading to repair defects or to skin injuries with unaesthetic alterations such as wrinkles. Knowing the intimate exchanges between the (myo)fibroblasts and their microenvironment represents a fascinating domain important not only for characterizing new targets and drugs able to prevent pathological developments but also for interfering with skin alterations observed during ageing.

22099332

The role of elastin peptides in modulating the immune response in aging and age-related diseases.

It is now well accepted that aging is associated with the occurrence of a low-grade inflammation called Inflamm-aging. This leads to the imbalance between the various mediators of the inflammatory response in favour of the pro-inflammatory response represented by pro-inflammatory cytokines and oxidative stress. The question that arises, and is still under investigation, what is the origin of the driving force leading to these changes. One of the current hypotheses is that chronic stimulation of the immune system contributes to the pro-inflammatory shift. The chronic stimulation can be of viral origin such as cytomegalovirus, from tumor antigens or from other sources such as the extracellular matrix, especially from elastin fibres and collagens. Aging and various inflammatory diseases such as atherosclerosis, abdominal aortic aneurysms, chronic obstructive pulmonary diseases (COPD), cancer and type 2 diabetes are characterized by the destruction of elastin fibers and the consequent generation of elastin peptides which are biologically active. This review will describe the putative contribution of elastin peptides to inflamm-aging and extend on their role on immunosenescence, as well as on age-associated chronic inflammatory diseases.

22099334

[Surgical excision of giant congenital naevi: how far can we go with surgery?].

Surgical excision of giant congenital nevi is mended by principle for dermatological reasons. Malignant potential is real but its incidence remains widely discussed. Their excision represents a surgical challenge but is also a real assault course for the child and his family. The sequelae and the psychological effects can be important. Can an plete excision to limit these aesthetic after-effects and relieve the surgical treatment be acceptable? We present the case of a child affected by a giant congenital nevi of the cephalic extremity where the excision was partial. A review of the literature on the degenerative risk of the giant congenital nevi allowed us of noticed that this one tends to be overestimated. The advantages and the disadvantages to practise a preventive, premature excision plete of the giant congenital nevi are approached. We discuss the possibility to resort to a partial excision in certain cases delicate of reconstruction under the cover of a strict and moved closer dermatological surveillance.

22099335

Correlation of vitamin A nutritional status on alpha-tocopherol in the colostrum of lactating women.

The adequate supply of vitamins A and E to newborns is essential. However, factors such as maternal nutritional status and nutrient interaction may limit its bioavailability. The aim of this study was to establish nutritional status for vitamins A and E and evaluate the correlation of retinol on colostrum alpha-tocopherol in lactating women. A total of 103 lactating women were recruited at a Brazilian public maternity hospital. Fasting serum and colostrum samples were collected in the immediate post-partum. Retinol and alpha-tocopherol levels were determined by high-performance liquid chromatography and nutritional status for these vitamins was defined from specific cut-off points for serum and colostrum. Mean serum and colostrum retinol (1.49 µmol L(-1) , 2.18 µmol L(-1) ) and alpha-tocopherol (26.4 µmol L(-1) , 26.1 µmol L(-1) ) indicated satisfactory biochemical status. However, we found a prevalence of subclinical deficiency of vitamin A and vitamin E in serum (15.5% and 16%) and colostrum (50% and 60%). Lactating women with serum retinol ≥ 1.05 µmol L(-1) showed an inverse correlation between serum retinol and alpha-tocopherol concentration in the colostrum (P = 0.008, r = -0.28). This association was not observed in serum level < 1.05 µmol L(-1) . The nutritional status of lactating women for vitamins A and E was adequate, although there is a risk of subclinical deficiency. The negative correlation of serum retinol on alpha-tocopherol concentration in the colostrum must be carefully evaluated in situations of vitamin A supplementation, because alpha-tocopherol bioavailability in maternal milk may promised.

22099337

Particle sizing of colloidal suspensions by low-coherence fiber optic dynamic light scattering.

A low-coherence fiber optic dynamic light scattering technique is used to measure the particle size distributions of colloidal suspensions with different volume fractions. We detect electric field autocorrelation function of the singly backscattered light from a sample and use the CONTIN algorithm to obtain the particle size distributions. As a result, in the range of volume fractions from 0.01 to 0.10 of monodispersive colloidal suspensions, the mean particle size with the deviation within 4% and the polydispersity approximate 5% can be determined for particles of different radii. The results demonstrate that the low-coherence fiber optic dynamic light scattering technique is effective in measuring particle size of colloidal suspensions.

22099336

Synthesis of a thermosensitive surface by construction of a thin layer of poly (N-isopropylacrylamide) on maleimide-immobilized polypropylene.

Thermosensitive surfaces were developed by the grafting of a thin layer of PNIPAAm through an UV-induced photopolymerization reaction of vinyl monomers with a free radical-activated polypropylene (PP) surface. PNIPAAm layer covering the PP surface corrected, to some extension, both depressions and fissures of the previously modified PP surfaces. The layered surfaces have morphological characteristic different from those of the non-layered surfaces, and their thickness was dependent on irradiation time. Water contact angles of the layered surfaces revealed a transition at approximately 33.5-36.5 °C as a result of a response to the variation of temperature. There was an increase in the values of the contact angles with an increase in temperature from 26 °C to 44 °C, revealing the nature both hydrophilic and hydrophobic of the surfaces due to a conformational rearrangement of PNIPAAm exposing its isopropyl groups to the liquid drop. This work offers a chemically stable thermosensitive surface (because it is covalently structured) with great potential for use as sensors and actuators.

22099339

The two faces of DOC.

Dissolved organic carbon (DOC), through its ability plex metals and thereby reduce their bioavailability, plays a major role in ameliorating metal toxicity in natural waters. Indeed DOC is a key variable in the Biotic Ligand Model (BLM) for predicting metal toxicity on a site-specific basis. However, recent evidence indicates that all DOCs are not alike, but rather heterogeneous in their ability to protect organisms against metal toxicity, at least in fresh water. The degree of protection appears to correlate with optical properties, such that dark, pounds of allochthonous origin, with greater humic acid content, are more effective in this regard, particularly against Cu, Ag, and Pb toxicity. The specific absorption coefficient of the DOC in the 300-350nm range (SAC(300-350)) has proven to be a simple and effective index of this protective ability. PARAFAC, a multivariate statistical technique for analysis of excitation-emission fluorescence spectroscopy data, also holds promise for quantifying the humic-like and fulvic-like fluorophores, which tend to be positively and negatively correlated with protective ability, respectively. However, what has been largely missing in the toxicological realm is any appreciation that DOC may also affect the physiology of target organisms, such that part of the protection may occur by a mechanism other than plexation. Recently published evidence demonstrates that DOC has effects on Na(+) transport, diffusive permeability, and electrical properties of the gills in fish and crustaceans in a manner which will promote Na(+) homeostasis. These actions could thereby protect against metal toxicity by physiological mechanisms. Future research should investigate potential direct interactions of DOC molecules with the branchial epithelium. Incorporation of optical properties of DOC could be used to improve the predictive capabilities of the BLM.

22099340

Incorporating exposure into aquatic toxicological studies: an imperative.

The field of aquatic toxicology has been expanding rapidly in recent years. The ecotoxicological study of environmental toxicants passes three basic frameworks: environmental behavior/transport, bioavailability/bioaccumulation (exposure), and toxicity at different biological levels. Environmental risk assessments are then based on this knowledge to provide sound advice for environmental management and policies. In this article I will highlight the need to further understand the exposure to toxicants and its direct relationship with toxicological responses at different levels. Exposure considerations generally include the route, species, concentration and duration of exposure, among which the importance of the exposure route has been little considered. A typical aquatic toxicological study simply exposes the organisms to toxicants in the water for a certain period of time under different concentrations. This approach may not be environmentally relevant. Future studies should attempt to understand the toxicology under different exposure regimes. Incorporating exposure will allow aquatic toxicology to be placed in a context of environmental relevance and enhance our understanding of the impacts of toxicants on our living environments.

22099342

Progress and promises in toxicogenomics in aquatic toxicology: is technical innovation driving scientific innovation?

In the last decade, new technologies have been invented to analyze large amounts of information such as gene transcripts (transcriptomics), proteins (proteomics) and small cellular molecules (metabolomics). Many studies have been performed in the last few years applying these technologies to aquatic toxicology, mainly in fish. In this article, we summarize the current state of knowledge and question whether the application of modern technology for descriptive purposes truly represents scientific advancement in aquatic toxicology. We critically discuss the advantages and disadvantages of these technologies and emphasize the importance of these critical aspects. To date, these techniques have been used mainly as a proof of principle, demonstrating effects of pounds. The potential to use these techniques to better analyze the mode-of-action of a toxicant or the effects of pound within organisms has rarely been met. This is partly due to a lack of baseline data and the fact that the expression of mRNA and protein profiles is rarely linked to physiology or toxicologically meaningful es. It seems premature to analyze mixtures or environmental samples until more is known about the expression profiles of individual toxicants. Gene transcription, protein, or metabolic data give only a partial view of these effects. Thus, we emphasize that data obtained by these technologies must be linked to physiological changes to fully understand their significance. The use of these techniques in aquatic toxicology is still in its infancy, data cannot yet be applied to environmental risk assessment or regulation until more emphasis is placed on interpreting the data within their physiological and toxicological contexts.

22099341

Functional genomics in aquatic toxicology-do not forget the function.

Toxicological responses of an organism are disturbances of function. This as a starting point we review and discuss issues that we consider important in applying functional genomics to aquatic toxicology. Functional genomics includes all the steps in gene expression pathway. Thus, ultimately the goal is to relate genome information to protein activity. In ecotoxicogenomics the toxicological responses must further bined with responses to natural environmental changes. We focus on fish, but also monly used invertebrates, mainly Daphnia. We first go through the toxicologically important features of genomes of aquatic animals, and then review the reference gene approach to quantify transcript amount. Thereafter we emphasize the need to relate the mRNA and protein levels, and protein activity of individual genes. Finally we discuss how functional genomic investigations may be important in resolving current environmental problems and give our views of valuable future research topics.

22099344

Moving beyond a descriptive aquatic toxicology: the value of biological process and trait information.

In order to improve the ability to link chemical exposure to toxicological and ecological effects, aquatic toxicology will have to move from observing what chemical concentrations induce adverse effects to more explanatory approaches, that are concepts which build on knowledge of biological processes and pathways leading from exposure to adverse effects, as well as on knowledge on stressor vulnerability as given by the genetic, physiological and ecological (e.g., life history) traits of biota. Developing aquatic toxicology in this direction faces a number of challenges, including (i) taking into account species differences in toxicant responses on the basis of the evolutionarily developed diversity of phenotypic vulnerability to environmental stressors, (ii) utilizing diversified biological response profiles to serve as biological read across for prioritizing chemicals, categorizing them according to modes of action, and for guiding targeted toxicity evaluation; (iii) prediction of ecological consequences of toxic exposure from knowledge of how biological processes and phenotypic traits lead to effect propagation across the levels of biological hierarchy; and (iv) the search for concepts to assess the cumulative impact of multiple stressors. An underlying theme in these challenges is that, in addition to the question of what the chemical does to the biological receptor, we should give increasing emphasis to the question how the biological receptor handles the chemicals, i.e., through which pathways the initial chemical-biological interaction extends to the adverse effects, how this extension is modulated by adaptive pensatory processes as well as by phenotypic traits of the biological receptor.

22099343

A genomic and ecotoxicological perspective of DNA array studies in aquatic environmental risk assessment.

Ecotoxicogenomics is developing into a key tool for the assessment of environmental impacts and environmental risk assessment for aquatic ecosystems. This review aims to report achievements and drawbacks of this technique and to explore potential conceptual and experimental procedures to improve future investigations. Ecotoxicogenomic literature evidences the ability of genomic technologies to characterize toxicant specific gene transcriptome patterns that can be used to identify major toxicants affecting aquatic species. They also contribute decisively to the development of new molecular biomarkers and, in many cases, to the determination of new possible gene targets. Primary transcriptomic responses obtained after short exposures provided more information of putative gene targets than secondary responses obtained after long, chronic exposures, which in turn are usually more accurate to describe actual environmental impacts in natural populations. Several problems need to be addressed in future investigations: the lack of studies (and genomic information) on key ecological species and taxa, the need to better understand the different transcriptomic responses to high and low doses and, especially, short and long exposures, and the need to improve experimental designs to minimize false transcriptome interpretations of target genes.

22099345

Molecular and biochemical biomarkers in environmental monitoring: a comparison of biotransformation and antioxidant defense systems in multiple tissues.

The cytochrome P450 pathway and antioxidant responses are known for their responsiveness to environmental pollutants and are frequently used as biomarkers at the transcriptional, translational and catalytic levels. Although molecular responses are often assumed to reflect similar changes in enzyme function, several factors can influence intracellular effects, including mRNA stability and protein turnover, signal sensing and transduction, post-translational modifications of proteins, and multiple mode of action of chemicals plex mixtures. The aim of this study was to use experimental data for a general discussion on the importance of mechanisms modulating transcriptional and catalytic responses of these pathways, and the resulting implications for environmental monitoring. The European eel Anguilla anguilla was selected as fish model pare the effects of polluted sediments on gene expression and functional levels of cytochrome P450, glutathione S-transferases, UDP-glucoronosyl transferases, catalase, glutathione peroxidases, superoxide dismutase, glutathione, glutathione reductase, glucose 6-phosphate dehydrogenase and γ-glutamylcysteine ligase in the liver and gills. The overall results confirmed significant changes in gene transcription related to biotransformation and oxyradical metabolism, but also supported the evidence of a frequent dissociation between mRNA expression and protein activity. More similar trends of variations and exposure-dependent relationships was observed in the liver for transcriptional and catalytic responses of those pathways closely regulated by specific interactions between substrate, transcription factors, gene and metabolizing protein (i.e. phase I and phase II). On the other hand, the lower metabolism and the cellular machinery of gill cells may prevent elevated transcriptional responsiveness to be translated to an adequate functional response of a protein. Relationships between transcriptional and catalytic effects were often inconsistent for antioxidant responses confirming plexity of interactions between exposure to chemical pollutants and regulation of oxidative stress responses. Oxidative stress responses may not necessarily be associated with transcriptional variations of genes, but rather with post-translational modifications of proteins. These mechanisms are just beginning to be revealed in marine organisms, but their characterization will be fundamental for better understanding of the implications of variations in gene expressions according to system, tissue, intensity and duration of exposure.

22099347

Cocktail effects on biomarker responses in fish.

One of today's greatest challenges in environmental toxicology is to understand effects of mixture monly referred to as cocktail effects, in humans and in wildlife. Biomarker responses in fish are routinely used to assess exposure of anthropogenic chemicals in the aquatic environment. However, little is known about how cocktail effects affect these biomarker responses. For this reason, there is an obvious risk for misinterpretation of biomarker-data and this can have profound negative effects on stakeholder's decisions and actions, as well as on legislations and remediation-plans initiated in order to reduce exposure to certain chemicals. Besides, chemical safety-levels are traditionally based on experiences from lab-studies with single chemicals, which is unfortunate as a chemical can be more toxic when it is mixed with other chemicals, because of the cocktail effect. This review focuses on pharmacokinetic interactions between different classes of pollutants on detoxification mechanisms and how that affects monly used biomarkers in the aquatic environment: (1) induction of cytochrome P450 1A (CYP1A) that is mediated via activation of the arylhydrocarbon receptor (AhR), used to assess exposure to aromatic hydrocarbons; (2) induction of vitellogenin (VTG) that is mediated via activation of the estrogen receptor (ER), used to assess exposure to estrogenic chemicals. These responses can be either directly or indirectly affected by the presence of other classes of pollutants as a result of cocktail effects. For example, chemicals that inhibit the function of key metabolic enzymes and transporter pumps that are involved in elimination of AhR- and ER agonists, can result in bioaccumulation of aromatic hydrocarbons and estrogenic chemicals resulting in increased biomarker responses. This cocktail effect can lead to overestimation of the actual exposure pressure. On the contrary, induction of expression of key metabolic enzymes and transporter activities can result in increased elimination of AhR- and ER agonists that can lead to possible underestimation of the exposure. Another type of cocktail effect is inhibiting receptor cross-talk that may cause decreased biomarker responses that can also lead to underestimation of the actual exposure. To address the possible involvement of pharmacokinetic interactions including receptor cross-talks, we need bine analyses on receptor signaling with studies on function of key biotransformation enzymes such as major catabolic CYP enzymes (e.g. CYP1-4) as well as efflux pumps (e.g. ATP-binding cassette transporter proteins). Besides, studies of inhibition of these enzymes and pumps activities pose a great potential to be used as future biomarkers as they are more clearly liked to adverse pared to for example induction of CYP1A and VTG expression.

22099348

Impacts of climate change on hypersaline conditions of estuaries and xenobiotic toxicity.

Climate change has had significant impacts on the hydrologic cycle of the planet. Of particular concern are estuarine environments, such as San Francisco Bay (USA) which is fed by diminishing snow pack runoff leading to gradual increases in salinity. Salinity enhances the acute toxicity of several agricultural chemicals in anadromous fish through augmented biochemical activation catalyzed by enzymes that are induced during hypersaline acclimation. This review discusses the mechanisms of the enhanced toxicity, the enzymes involved and the regulation of the enzymes by hypersaline conditions. Given the rapid changes taking place in the world's waterways, environmental modification of toxicological pathways should be a significant focus of the munity as the toxicity of multiple xenobiotics may be enhanced.

22099346

Mechanistic research in aquatic toxicology: perspectives and future directions.

On the 30th anniversary of the journal, I provide a perspective on some of the questions and opportunities for new understanding that will interest aquatic toxicologists during the next 30 years. I focus on mechanisms of toxicity involving transcription factors, signalling pathways, and gene networks involved in toxic and adaptive responses in aquatic animals. Prominent questions address the value of a toxicity pathways approach in aquatic systems, issues involving extrapolation among species, identification of susceptibility genes and useful biomarkers of adverse effect, new emerging contaminants, the importance of epigenetic mechanisms, effects of multiple stressors, evolutionary toxicology, and the relative roles of technical and conceptual limitations to our understanding of chemical effects on aquatic systems.

22099350

Peptidoglycan recognition protein 3 (PglyRP3) has an anti-inflammatory role in intestinal epithelial cells.

Intestinal epithelial cells produce cytokines in response to bacterial peptidoglycan (PGN), which is detected by several classes of pattern-recognition receptors (PRRs) as peptidoglycan recognition proteins (PGlyRPs), Toll-like receptor 2 (TLR2) and NOD receptors. All types of PGlyRPs recognize bacterial peptidoglycan and function in antibacterial innate immunity. In this study, we investigated the role of PGlyRP3 in the response of intestinal epithelial cells (Caco-2) to PGN from pathogenic (Staphylococcus aureus), opportunistic pathogenic (Micrococcus luteus) and non-pathogenic (Bacillus subtilis and Lactobacillus rhamnosus GG) bacteria found in the gut mensals or in gastroenteritis. All PGNs induced the proinflammatory cytokines IL-12p35, IL-8 and TNF-α and, time-dependently, PGlyRP3, at both the transcription and protein levels. In this context, no differences were observed among the distinct PGN obtained from different bacterial sources. The inflammatory response to PGN is mediated via the TLR2 pathway, since blocking this pathway by inhibiting MyD88 reduced the expression of proinflammatory cytokines. In addition, PGlyRP3 overexpression suppressed, while PGlyRP3 knocking down enhanced the expression of PGN-induced inflammatory cytokines. It is concluded that PGN stimulates inflammatory responses in the intestinal epithelia through activation of the TLR pathway. PGlyRP3 is also stimulated by PGN and has, in contrast to activation of the TLR pathway, an anti-inflammatory effect.

22099351

A balance between tissue-destructive and tissue-protective immunities: a role of toll-like receptors in regulation of adaptive immunity.

The immune system has been shown to be involved in not only the host defense against infectious pathogens but also in tissue repair processes continuously occurring in the body. Our review presents the hypothesis about the mechanism of TLR-mediated regulation of adaptive immune responses linked to the tissue destruction. In our opinion following injury to a tissue, the expression of tissue-specific determinant/MHC class plexes on dendritic cells and macrophages are upregulated significantly due to the increased uptake of tissue debris. Consequently, T-cells e activated as a result of low affinity, but high avidity interactions between self-reactive CD4+T cells and antigen-presenting cells (APCs). The type of self antigen-induced immune responses depends on the multiple downstream signals generated by intracellular toll-like receptors (TLRs) 3, 7, 8, and 9, that discriminate "self" and "non-self" nucleic acids. Accumulating data suggest that ligation of intracellular TLRs by endogenous DNA/RNA released from necrotic cells may result in developing Th2-like responses, as well as in the alternative activation of macrophages (M2), that favor local tissue protection pensatory cell growth. In contrast, ligation of intracellular TLRs by exogenous pathogen-derived DNA/RNA may promote Th1-driven responses, as well as classical activation of macrophages (M1), that contribute to local tissue destruction and suppress cell growth. We suggest here that the balance between the host- and pathogen-derived nucleic acids interacting with intracellular TLRs contributes to the balance between immune-mediated tissue-protective and tissue-destructive events occurring in the body.

22099352

Muscular strengthening activity patterns and metabolic health risk among US adults.

Many studies have examined the relationship between physical activity and metabolic disorders. However, few have focused on specific associations between these disorders and muscular strengthening activity (MSA) patterns. The aim of the present study was to examine the association(s) for each metabolic syndrome criterion and MSA patterns.

22099354

Knowledge and therapeutic gaps: a public health problem in the rare coagulation disorders population.

Rare coagulation disorders (RCDs) present a considerable and multifaceted public health risk. Although inherited RCDs affect a minor segment of any local healthcare delivery system, their global impact is major and highlight the challenges of delivering healthcare services to any rare disease population. These include but are not limited to: (1) a general lack of knowledge about and familiarity with the genetic and clinical implications of the disorder among affected patients, and both urgent and specialty care providers; (2) the potential for preventable morbidity and mortality related to delayed diagnosis and treatment; (3) the lack of safe and effective therapies; and (4) minimal research activity to establish and improve standards of care. A multiagency national partnership has established an approach to address these problems through development of a clinical, genetic, and treatment-related web-based data-collection tool that will: (1) generate a reliable, sufficient knowledge base for these disorders; (2) facilitate new product licensure through subject identification and access parative historical treatment data; and (3) serve as an effective tool for es research and post-licensure product surveillance. To maximize impact, this database is being harmonized with a European data-collection effort. Database development and harmonization is in progress. A resource library pleted and disseminated to major national and international bleeding disorder websites to provide state-of-the-art patient and provider education on each RCD. We believe that this model is effective and adaptable to other rare conditions.

22099355

A community-based partnership to promote information infrastructure for bleeding disorders.

Specialists in rare disorders often face challenges in collecting surveillance and research data. As movement toward more fully realizing the potential of electronic health information gains momentum, practitioners who treat individuals with rare disorders are in need of public-private support to tap into the advantages offered by the developing electronic information technologies and the interoperability standards promulgated by the USDHHS. The not-for-profit American Thrombosis and Hemostasis Network (ATHN) was created in 2006 to provide stewardship of a secure, national, web-based database to support federally funded hemophilia treatment centers (HTCs) across the country. In pursuit of its mission to support clinical es analysis, research, advocacy, and public health reporting in the hemostasis and munity, ATHN has established a spectrum munity-based partnerships. This paper describes the process and public health benefits of creating formal relationships with 127 of the 134 HTCs from 12 regional networks across the U.S., government agencies such as the CDC, Health Resources and Services Administration, and NIH; consumer-based organizations; and industry leaders. munity-based partnership model can be applied to other rare munities with high economic and public health impact.

22099356

Insurance, home therapy, and prophylaxis in U.S. youth with severe hemophilia.

Home infusion therapy, particularly on a prophylactic regimen, is linked with reduced morbidity among youth with severe hemophilia. However, the association of insurance coverage with these home therapies is unknown.

22099357

Self-reported barriers to hemophilia care in people with factor VIII deficiency.

In 1975, a national network of hemophilia treatment centers (HTCs) was created to increase access to healthcare services for individuals with hemophilia. Studies demonstrate that care in HTCs improves es and reduces costs.

22099359

Physical functioning in boys with hemophilia in the U.S.

Hemophilia is the mon inherited severe bleeding disorder. Although the most plication of repeated hemorrhages is a crippling joint disease that begins in childhood, the extent of resultant joint functional impairment varies widely within the hemophilia population.

22099358

Surveillance of bleeding disorders, Texas, 2007.

In 2007, some 1261 patients with hemophilia or other bleeding disorders were seen at federally funded hemophilia treatment centers (HTCs) in Texas. Although HTCs function as sites for passive surveillance of bleeding disorders, annual HTC visit data likely underestimate true prevalence of the disease due to the infrequent nature of healthcare utilization for this population.

22099360

Overweight and obesity in hemophilia: a systematic review of the literature.

As life expectancy in individuals with congenital hemophilia approaches that of the general population, we hypothesize that public health risks, including overweight and obesity, also follow a similar trend.

22099361

Sickle cell disease: the need for a public health agenda.

Sickle cell disease (SCD) is a collection of inherited blood disorders that affect a substantial number of people in the U.S., particularly African Americans. People with SCD have an abnormal type of hemoglobin, Hb S, which polymerizes when deoxygenated, causing the red blood cells to e misshapen and rigid. Individuals with SCD are at higher risk of morbidity and mortality from infections, vaso-occlusive pain crises, acute chest syndrome, and plications. Addressing the public health needs related to SCD is an important step toward improving es and maintaining health for those affected by the disorder. The objective of this study was to review public health activities focusing on SCD and define the need to address it prehensively from a public health perspective. We found that there has been some progress in the development of SCD-related public health activities. Such activities include establishing newborn screening (NBS) for SCD with all states currently having universal NBS programs. However, additional areas needing focus include strengthening surveillance and monitoring of disease occurrence and health es, enhancing adherence to health maintenance guidelines, increasing knowledge and awareness among those affected, and improving healthcare access and utilization. These and other activities discussed in this paper can help strengthen public health efforts to address SCD.

22099362

Hemoglobinopathy newborn screening knowledge of physicians.

Hawai'i has a diverse population, including many individuals of Asian descent. A relatively high proportion of Hawai'i infants are born with inherited hemoglobinopathies; about 2% have α-thalassemia trait. The Hawai'i Genetics Program engages in genetics services and public health activities, including a hemoglobinopathy clinic and provider education.

22099363

Disability among individuals with sickle cell disease: literature review from a public health perspective.

Young people with blood disorders face challenges in maintaining their physical health as they age. Sickle cell disease has plications in various organ systems. Increasingly, professionals, consumers, and advocates involved in blood disorders are concerned about the cumulative and ongoing effect of plications on function and participation.

22099364

Sickle cell disease in Africa: a neglected cause of early childhood mortality.

Sickle cell disease (SCD) mon throughout much of sub-Saharan Africa, affecting up to 3% of births in some parts of the continent. Nevertheless, it remains a low priority for many health ministries. The mon form of SCD is caused by homozygosity for the β-globin S gene mutation (SS disease). It is widely believed that this condition is associated with very high child mortality, but reliable contemporary data are lacking. We have reviewed available African data on mortality associated with SS disease from published and unpublished sources, with an emphasis on two types of studies: cross-sectional population surveys and cohort studies. We have concluded that, although current data are inadequate to support definitive statements, they are consistent with an early-life mortality of 50%-90% among children born in Africa with SS disease. Inclusion of SCD interventions in child survival policies and programs in Africa could benefit from more precise estimates of numbers of deaths among children with SCD. A simple, representative, and affordable approach to estimate SCD child mortality is to test blood specimens already collected through large population surveys targeting conditions such as HIV, malaria, and malnutrition, and covering children of varying ages. Thus, although there is enough evidence to justify investments in screening, prophylaxis, and treatment for African children with SCD, better data are needed to estimate the numbers of child deaths preventable by such interventions and their cost effectiveness.

22099365

Screening U.S. college athletes for their sickle cell disease carrier status.

There are many issues surrounding the screening of collegiate athletes for their sickle cell disease carrier status (or sickle cell trait), a genetic condition. This paper summarizes the establishment of expert advice given to the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children (SACHDNC) on the issue. The SACHDNC has developed a report to advise the Secretary of the USDHHS about the 2010 rule of the National Collegiate Athletic Association (NCAA) requiring testing for sickle cell trait in all ing Division I student athletes. The SACHDNC does not support the NCAA's rule to screen collegiate athletes for sickle cell trait.

22099367

Concerted global effort to combat sickle cell disease: the first global congress on sickle cell disease in Accra, Ghana.

The First Global Congress on Sickle Cell Disease was held in Accra, Ghana, on July 20-23, 2010, memorate 100 years since the first published report of sickle cell disease (SCD). The idea of the Global Congress was conceived following the 2007 meeting in Nicosia, Cyprus, jointly organized by the WHO and the Thalassaemia International Federation (TIF), which mended that groups working in SCD around the world needed to consolidate efforts into a stronger and more unified umbrella organization. The need for a united global effort received further endorsements at the 2009 International Symposium and Workshop held in Cotonou, Benin, and the 2009 memoration of World Sickle Cell Disease Awareness Day, UN Headquarters, New York, New York. The overall goals of the Global Congress were to promote international cooperation and foster collaboration in advancing clinical care and furthering basic and applied research in SCD. Issues covered at the conference included health education, psychosocial needs, public health, medical care, research, program development, and development of munity-based organizations. The Congress participants included medical and research scientists, public health munity-based SCD organizations, other nongovernmental organizations, and people with SCD and their families. The Congress concluded with a call on patients and families affected by SCD, as well as advocacy groups, healthcare professionals, scientists, and national governments working bat SCD to endorse the formation of the World Sickle Cell Disease Federation.

22099368

Iron overload: what is the role of public health?

Hereditary hemochromatosis type 1, also known as hereditary hemochromatosis classical (HHC), is an iron overload disorder associated, in most cases, with mutations of the hemochromatosis (HFE) gene. Although suggested algorithms for diagnosing iron overload are available, there are still questions about options for genetic and biochemical screening for hemochromatosis and duration of treatment. This article provides a summary of an expert workgroup meeting convened on September 24-25, 2009, entitled "Iron Overload: What is the Role of Public Health?" The purpose of the meeting was to enable subject matter experts to share their most recent clinical and scientific iron overload information and to facilitate the discussion of future endeavors, with special emphasis on the role of public health in this field. The two main topics were the research priorities of the field, including clinical, genetic, and public health issues, and the concerns about the validity of current screening mendations for the condition.

22099369

Developing public health surveillance for deep vein thrombosis and pulmonary embolism.

Deep vein thrombosis (DVT) and pulmonary embolism (PE), collectively known as venous thromboembolism (VTE), are an important and growing public health issue, associated with considerable morbidity and mortality. Presently, there is no national surveillance for DVT and PE. This article provides a summary of an expert workgroup meeting convened January 12, 2010, by the CDC. The purpose of the meeting was to inform CDC on the development of U.S. population-based public health surveillance activities for DVT/PE. Topics discussed included: (1) stakeholders, needs, gaps, and target populations; (2) requirements of surveillance systems; (3) challenges, limitations, and potential barriers to implementation of surveillance activities; and (4) integration of research and education with surveillance activities.

22099370

Public health implications of sickle cell trait: a report of the CDC meeting.

Although the issue of whether sickle cell trait (SCT) is clinically benign or a significant health concern has not yet been resolved, the potential health risk to affected individuals is of vital importance and represents a tremendous challenge in protecting, promoting, and improving the health of the approximately 300 million people worldwide and 3 million people in the U.S. who possess the trait. In response to a request by the Sickle Cell Disease Association of America, in December 2009, the CDC convened a meeting of partners, stakeholders, and experts to identify the gaps in public health, clinical health services, epidemiologic research, munity-based outreach strategies and to develop an agenda for future initiatives. Through facilitated discussion and presentations in four topic areas, participants discussed pertinent issues, synthesized clinical research findings, and developed a coherent framework for establishing an agenda for future initiatives. A primary e of the meeting was to provide the first step of an iterative process to move toward agreement regarding appropriate counseling, care, and, potentially, treatment of people with SCT.

22099371

Management of severe acute to fulminant hepatitis B: to treat or not to treat or when to treat?

Despite a decline in cases of acute hepatitis B and the low hepatitis B virus (HBV) chronicity rates in adults, still some patients progress to HBV-related fulminant liver failure. In this review, we discuss treatment options that may prevent the progression of severe acute hepatitis B to fulminant liver failure and death. In severe acute HBV with prolonged prothrombin time and increased bilirubin, interferon failed to be effective while antiviral treatment, particularly with lamivudine, appears to improve survival (mean survival almost 80%). e without antiviral therapy has remained considerably poor, whereas there is no convincing evidence of amelioration of HBV-targeted immunity. Of note, most patients who died or required transplantation despite lamivudine therapy, were started on lamivudine at advanced pared with those survived. This suggests that prompt and timely antiviral therapy is crucial. Owing to the abovementioned results the design of randomized placebo-control trials in the setting of severe acute hepatitis B seems unethical. On the contrary, the design of multicentre double-blind randomized trials pare the efficacy between lamivudine and entecavir or even tenofovir in acute severe HBV cases is ideally needed, but these studies appear to be very difficult to perform considering that these cases are not frequent and therefore, it is almost impossible to have two arms adequately numerous and homogenous for statistical evaluation. Thus, in the absence of solid evidence based data, the hepatologists could treat their patients with severe acute hepatitis B with lamivudine or the most potent antivirals entecavir or tenofovir.

22099373

l-Arabinose production from sugar beet arabinan by immobilized endo- and exo-arabinanases from Caldicellulosiruptor saccharolyticus in a packed-bed reactor.

The immobilized endo- and exo-arabinanases from Caldicellulosiruptor saccharolyticus produced continuously an average of 16.5 gl(-1)l-arabinose from 20 gl(-1) sugar beet arabinan at pH 5.0 and 75°C for 216 h, with a productivity of 9.9 gl(-1)h(-1) and a conversion yield of 83%.

22099374

Stability of lactobacilli encapsulated in various microbial polymers.

Various microbial polymers, namely xanthan gum, gellan gum, pullulan gum and jamilan, were tested as a suitable encapsulating material for Lactobacillus plantarum CRL 1815 and Lactobacillus rhamnosus ATCC 53103. Resulting capsules were also studied for their pH and simulated gastrointestinal conditions tolerance. The morphology of the microcapsules was studied using scanning electron microscopy. pH tolerance was tested at pH 2.0, 3.5, 5.0 and 6.5 over a 6h incubation period. Simulated gastrointestinal conditions were assayed with simulated gastric and pancreatic juices and simulated bile over a 24h incubation period. Suspensions of probiotic organisms were used as a control. The results from encapsulation with microbial polymers indicate that mixtures of 1% xanthan gum with 0.75% gellan gum and 1% jamilan with 1% gellan gum were the most suitable for microencapsulation. Results for the pH tolerance tests showed no improvement in the viability of cells in relation to the control, except for pH 2.0 where lactobacilli encapsulated in xanthan:gellan gum (1%:0.75%) prolonged their viability by 6h exposure. Xanthan:gellan gum (1%:0.75%) was the most effective of the encapsulating materials tested in protecting L. plantarum and L. rhamnosus against simulated bile, improving its viability in 1-2 logCFU pared with control. The results of this study suggest that microbial polymers are an interesting source of encapsulating material that should be taken into account for prospective studies of probiotic encapsulation for oral delivery applications.

22099375

Metabolic engineering of hydrophobic Rhodococcus opacus for biodesulfurization in oil-water biphasic reaction mixtures.

An organic solvent-tolerant bacterium, Rhodococcus opacus B-4, was metabolically engineered to remove sulfur from dibenzothiophene (DBT), ponent of crude oil. The resulting binant strain ROD2-8 constitutively expressed the Rhodococcus erythropolis IGTS8 genes dszA, dszB, and dszC, encoding dibenzothiophene sulfone monooxygenase, 2-(2'-hydroxyphenyl) benzenesulfinate desulfinase, and dibenzothiophene monooxygenase, respectively, of the 4S pathway to avoid transcriptional inhibition by the sulfate end-product. Unlike the wild-type strain, ROD2-8 grew in mineral salts medium containing DBT as the sole sulfur source. Under aqueous conditions, ROD2-8 resting cells converted greater than 85% of DBT to 2-hydroxybiphenyl (2-HBP), although the consumption rate by ROD2-8 cells precultured on DBT as the sole sulfur source was 3.3-fold higher than that of cells cultured plex medium. Notably, DBT consumption rates increased by 80% in oil-water biphasic reaction mixtures with n-hexadecane as the organic solvent, and resting cells were predominantly localized in the emulsion layer. Desulfurization activity in biphasic reaction mixtures increased with increasing concentrations of DBT and was not markedly inhibited by 2-HBP accumulation. Intracellular concentrations of DBT and 2-HBP were significantly lower under biphasic conditions than aqueous conditions. Our findings suggest that the enhanced desulfurization activity under biphasic conditions results from bined effects of attenuated feedback inhibition and reduced mass transfer limitations due to 2-HBP diffusion from cells and accumulation of both substrate and biocatalyst in the emulsion layer, respectively. Therefore, the solvent-tolerant and hydrophobic bacterium R. opacus B-4 appears suitable for biodesulfurization reactions in solvents containing a minimum ratio of water.

22099376

Intracellular co-expression of Vitreoscilla hemoglobin enhances cell performance and β-galactosidase production in Pichia pastoris.

Pichia pastoris has been used to produce various binant proteins under high oxygen demand conditions. To improve the heterologous production of β-galactosidase, the vgb gene encoding Vitreoscilla hemoglobin (VHb) was co-expressed in the P. pastoris cytoplasm under the control of the methanol-inducible promoter. Co-expression of VHb under different aeration conditions improved cell performance in terms of growth, viability, respiratory rate, and β-galactosidase production. Under limiting aeration conditions, the VHb(+) strain produced 28.2% more biomass but 31.2% less total β-galactosidase activity than the VHb(-) strain. Under non-limiting aeration conditions, the VHb(+) strain showed 20.3% higher cell growth and 9.9% more total β-galactosidase activity than the VHb(-) strain. Moreover, under these conditions, the VHb(+) strain was 7.7% more viable and had a 28.2% higher oxygen uptake rate (OUR) than the VHb(-) strain. Evidently, VHb can enhance the OUR and promote methanol metabolism, thereby improving cell performance and β-galactosidase production.

22099377

Efficient propagation of archetype BK and JC polyomaviruses.

BKPyV and JCPyV are closely related, ubiquitous human pathogens that cause disease in promised patients. The DNA sequence of the regulatory regions distinguishes two forms of these viruses, designated archetype and rearranged. Although cell culture systems exist for rearranged BKPyV and JCPyV, currently there is no robust cell culture system to study the archetype viruses. Large T antigen (TAg) is a virally encoded protein required to initiate viral DNA synthesis. Because archetype virus produces undetectable levels of TAg, we hypothesized that TAg overexpression would stimulate archetype virus replication. Efficient propagation of the archetype forms of BKPyV and JCPyV was observed in 293TT cells, human embryonic kidney cells overexpressing SV40 TAg. Importantly, the archetypal structure of the regulatory region was maintained during viral growth. Significant replication was not observed for Merkel cell, KI, or WU polyomaviruses. 293TT cells provide a means of propagating archetype BKPyV and JCPyV for detailed study.

22099378

An adaptive mutation in NS2 is essential for efficient production of infectious 1b/2a chimeric hepatitis C virus in cell culture.

The development of JFH1 based intergenotypic binants which exploit the unique replication characteristics of JFH1 has made it possible to study infectious HCV encoding the structural genes of additional HCV genotypes including genotype 1b. Although, intergenotypic 1b/2a chimeric genomes replicate efficiently in transfected cells they produce very low viral titers, limiting the utility of this system. Here, intergenotypic 1b/2a variants were generated by serially passaging the virus in a novel highly permissive Huh-7 cell clone. The adapted virus was 1000-fold more infectious than the parental unadapted virus and six adapted mutations were identified throughout the genome. Of the mutations identified, L839S in the NS2 gene was the most critical for the adapted phenotype by enhancing the infectivity of assembled viral particles. Overall, the efficient production of infectious 1b/2a virus particles will facilitate the discovery and characterization of inhibitors targeting steps that involve the structural genes of genotype 1b HCV.

22099380

An improved rapid method for the preparation of D-rhamnose.

A method is developed for the preparation of D-rhamnose from an O-polysaccharide (OPS) isolated by mild acid hydrolysis of Azospirillum brasilense SR75 cell mass. After the OPS hydrolysis, D-rhamnose was recovered by gel-permeation chromatography on Toyopearl TSK HW-40 and was crystallized. The sugar activity was demonstrated immunochemically. The advantages of the method are that it expedites and simplifies the extraction of D-rhamnose and increases its yield.

22099381

Structure of the O-polysaccharide from the lipopolysaccharide of Providencia alcalifaciens O48.

An O-polysaccharide was isolated by mild acid degradation of the lipopolysaccharide of Providencia alcalifaciens O48 and studied by sugar and methylation analyses along with (1)H and (13)C NMR spectroscopy, including 2D COSY, TOCSY, ROESY and (1)H,(13)C HSQC and HMBC experiments. It was found that the polysaccharide is acidic and has a linear mono-O-acetylated tetrasaccharide repeating unit with the following structure: →3)-α-D-Manp-(1→2)-α-L-Fucp-(1→2)-β-D-GlcpA4Ac-(1→3)-α-D-GalpNAc-(1→.

22099382

Synthesis and characterization of pH-sensitive hydrogel composed of carboxymethyl chitosan for colon targeted delivery of ornidazole.

In the present study, carboxymethyl chitosan was prepared from chitosan, crosslinked with glutaraldehyde and evaluated in vitro as a potential carrier for colon targeted drug delivery of ornidazole. Ornidazole was incorporated at the time of crosslinking of carboxymethyl chitosan. The chitosan was evaluated for its degree of deacetylation (DD) and average molecular weight; which were found to be 84.6% and 3.5×10(4) Da, respectively. The degree of substitution on prepared carboxymethyl chitosan was found to be 0.68. All hydrogel formulations showed more than 85% and 74% yield and drug loading, respectively. The swelling behaviour of prepared hydrogels checked in different pH values, 1.2, 6.8 and 7.4, indicated pH responsive swelling characteristic with very less swelling at pH 1.2 and quick swelling at pH 6.8 followed by linear swelling at pH 7.4 with slight increase. In vitro release profile was carried out at the same conditions as in swelling and drug release was found to be dependant on swelling of hydrogels and showed biphasic release pattern with non-fickian diffusion kinetics at higher pH. The carboxymethylation of chitosan, entrapment of drug and its interaction in prepared hydrogels were checked by FTIR, (1)H NMR, DSC and p-XRD studies, which confirmed formation of carboxymethyl chitosan from chitosan and absence of any significant chemical change in ornidazole after being entrapped in crosslinked hydrogel formulations. The surface morphology of formulation S6 checked before and after dissolution, revealed open channel like pores formation after dissolution.

22099383

Isolation of human nasoseptal chondrogenic cells: a promise for cartilage engineering.

In cartilaginous tissues, perichondrium cambium layer may be the source of new cartilage. Human nasal septal perichondrium is considered to be a homogeneous structure in which some authors do not recognize the perichondrium internal zone or the cambium layer as a layer distinct from adjacent cartilage surface. In the present study, we isolated a chondrogenic cell population from human nasal septal cartilage surface zone. Nasoseptal chondrogenic cells were positive for surface markers described for mesenchymal stem cells, with exception of CD146, a perivascular cell marker, which is consistent with their avascular niche in cartilage. Although only Sox-9 was constitutively expressed, they also revealed osteogenic and chondrogenic, but not adipogenic, potentials in vitro, suggesting a more restricted lineage pared to mesenchymal stem cells. Interestingly, even in absence of chondrogenic growth factors in the pellet culture system, nasoseptal chondrogenic cells had a capacity to synthesize sulfated glycosaminoglycans, large amounts of collagen type II and to a lesser extent collagen type I. The spontaneous chondrogenic potential of this population of cells indicates that they may be a possible source for cartilage tissue engineering. Besides, the pellet culture system using nasoseptal chondrogenic cells may also be a model for studies of chondrogenesis.

22099384

Impact of polydextrose on the faecal microbiota: a double-blind, crossover, placebo-controlled feeding study in healthy human subjects.

In this placebo-controlled, double-blind, crossover human feeding study, the effects of polydextrose (PDX; 8 g/d) on the colonic position, immune parameters, bowel habits and quality of life were investigated. PDX is plex glucose oligomer used as a sugar replacer. The main goal of the present study was to identify the microbial groups affected by PDX fermentation in the colon. PDX was shown to significantly increase the known butyrate producer Ruminococcus intestinalis and bacteria of the Clostridium clusters I, II and IV. Of the other microbial groups investigated, decreases in the faecal Lactobacillus-Enterococcus group were demonstrated. Denaturing gel gradient electrophoresis analysis showed that bacterial profiles between PDX and placebo treatments were significantly different. PDX was shown to be slowly degraded in the colon, and the fermentation significantly reduced the genotoxicity of the faecal water. PDX also affected bowel habits of the subjects, as less abdominal fort was recorded and there was a trend for less hard and more formed stools during PDX consumption. Furthermore, reduced snacking was observed upon PDX consumption. This study demonstrated the impact of PDX on the colonic microbiota and showed some potential for reducing the risk factors that may be associated with colon cancer initiation.

22099387

Impact of medication adherence on health care utilization and productivity: self-reported data from a cohort of postmenopausal women on osteoporosis therapy.

Many pharmacologic agents are approved for the prevention and treatment of osteoporosis, which mon among postmenopausal women. Evidence exists relating treatment persistence to fracture risk. Less is known about treatment persistence and the use of health care service and individual productivity.

22099388

Quality evaluation of microscopy and scanned histological images for diagnostic purposes.

In this work we present a study for assessing paring the fidelity of biopsy and cytology images captured with two different devices, that is optical microscopes and scanners, at 40× magnification in bright field. The devices use different ways to magnify images. Microscopes use a set of lenses while scanners capture light through arrays of micro-photoreceptors. The objective is to carry out a quantitative evaluation to discern which of the two devices provides better image quality in terms of contrast, colour and stain. Since there is no unanimous consensus on quality metrics, we will make use of both an objective metric based on perceptual features, together with a subjective psychophysical test as the International munications Union (ITU) mends in ITU-R BT.500 for such type of tests. Both techniques indicate a slight preference for the scanner over the microscope in terms of better image quality, considering defocus as the main problem followed by colour distortions. However, the image quality of both devices is suitable for clinical, educational and research purposes.

22099389

Analysis on surface nanostructures present in hindwing of dragon fly (Sympetrum vulgatum) using atomic force microscopy.

The present study involves the analysis of surface nanostructures and its variation present in the hind wing of dragon fly (Sympetrum vulgatum) using atomic force microscopy (AFM). The hindwing was dissected into 4 parts (D1-D4) and each dissected section was analyzed using AFM in tapping mode at different locations. The AFM analysis revealed the presence of irregular shaped nanostructures on the surface of the wing membrane with size varying between 83.25±1.79 nm to 195.08±10.25 nm. The size and shape of the nanostructure varied from tip (pterostigma) to the costa part. The membrane surface of the wing showed stacked arrangement leading to increase in size of the nanostructure. Such arrangement of the nanostructures has lead to the formation of nanometer sized valleys of different depth and length on the membrane surface giving them ripple wave morphology. The average roughness of the surface nanostructures varied from 18.58±3.12 nm to 24.25±8.33 nm. Surfaces of the wings had positive skewness in D1, D2 and D4 regions and negative skewness in D3 region. These surface nanostructures may contribute asymmetric resistance under mechanical loading during the flight by increasing the bending and torsional resistance of the wing.

22099391

Brief review on systematic hypothermia for the protection of central nervous system during aortic arch surgery: a double-sword tool?

Antegrade selective cerebral perfusion in conjunction with hypothermia attenuate postoperative neurological injury, which in turn still remains the main cause of mortality and morbidity following aortic arch surgery. Hypothermic circulatory arrest however could be a useful tool during arch surgery, surgery for chronic thromboembolic disease, air on the arterial line during CPB, during cavotomy for extraction of renal cell carcinoma with level IV extension, or when dealing with difficult trauma to the SVC or IVC. Cerebral protective effects with hypothermic procedures including inhibition of neuron excitation, and discharge of excitable amino acids, and thereby, prevention of an increase in intercellular calcium ions, hyperoxidation of lipids in cell membranes, and free radical production.The authors are briefly discussing the fundamental principles of using hypothermia as an adjunct tool of the cardiothoracic surgeon's practice. The relationship between temperature, flow, metabolic requirements and adverse effects is addressed.

22099392

DNA-nanostructure-assembly by sequential spotting.

The ability to create nanostructures with biomolecules is one of the key elements in nanobiotechnology. One of the problems is the expensive and mostly custom made equipment which is needed for their development. We intended to reduce material costs and aimed at miniaturization of the necessary tools that are essential for nanofabrication. Thus bined the capabilities of molecular ink lithography with DNA-self-assembling capabilities to arrange DNA in an independent array which allows addressing molecules in nanoscale dimensions.

22099393

Medical marijuana laws in 50 states: investigating the relationship between state legalization of medical marijuana and marijuana use, abuse and dependence.

Marijuana is the most frequently used illicit substance in the United States. Little is known of the role that macro-level factors, munity norms and laws related to substance use, play in determining marijuana use, abuse and dependence. We tested the relationship between state-level legalization of medical marijuana and marijuana use, abuse, and dependence.

22099394

PP3 forms stable tetrameric structures through hydrophobic interactions via the C-terminal amphipathic helix and undergoes reversible thermal dissociation and denaturation.

The milk protein proteose ponent 3 (PP3), also called lactophorin, is a small phosphoglycoprotein that is expressed exclusively in lactating mammary tissue. The C-terminal part of the protein contains an amphipathic helix, which, upon proteolytic liberation, shows antibacterial activity. Previous studies indicate that PP3 forms multimeric structures and inhibits lipolysis in milk. PP3 is the ponent of the proteose peptone fraction of milk. This fraction is obtained by heating and acidifying skimmed milk, and in the dairy industry milk products are also typically exposed to treatments such as pasteurization, which potentially could result in irreversible denaturation and inactivation of ponents. We show here, by the use of CD, that PP3 undergoes reversible thermal denaturation and that the α-helical structure of PP3 remains stable even at gastric pH levels. This suggests that the secondary structure survives treatment during the purification and possibly some of the industrial processing of milk. Finally, asymmetric flow field-flow fractionation and multi-angle light scattering reveal that PP3 forms a rather stable plex, which dissociates and unfolds in guanidinium chloride. The cooperative unfolding of PP3 pletely removed by the surfactant n-dodecyl-β-d-maltoside and by oleic acid. We interpret this to mean that the PP3 monomers associate through hydrophobic interactions via the hydrophobic surface of the amphipathic helix. These observations suggest that PP3 tetramers act as reservoirs of PP3 molecules, which in the monomeric state may stabilize the milk fat globule.

22099396

Assessing smoking status in disadvantaged populations: is computer administered self report an accurate and acceptable measure?

Self report of smoking status is potentially unreliable in certain situations and in high-risk populations. This study aimed to determine the accuracy and acceptability puter administered self-report of smoking status among a low socioeconomic (SES) population.

22099401

[Indications for surgery in non-small cell lung cancer with lymph node invasion].

Surgery is indicated for N1 non-small cell lung cancer and performed, with good results in some patients, when N2 disease is not diagnosed preoperatively "minimal N2". Following the publication of the "EORTC 08941" and "Intergroup 0139" trials, it remains debatable for patients with proven N2 disease. Good prognostic factors before treatment or post-induction favour surgery, which seems superior to radiochemotherapy if the operative risk is low (lobectomies, and some pneumonectomies). N3 status is a contraindication to surgery, except in some rare cases with a strong response to induction treatment.

22099397

BMP-7/TGF-β1 signalling in myoblasts: components involved in signalling and BMP-7-dependent blockage of TGF-β-mediated CTGF expression.

We and others have recently described the antagonistic role of Bone morphogenetic protein-7 (BMP-7) in TGF-β signalling and myogenic differentiation. To specify the underlying mechanism(s), we here analysed the expression and function of the ponents mediating TGF-β1 and BMP-7 responses. We found that BMP-7 at a concentration of 25 ng/ml induces signalling exclusively via ALK2 and ALK3 leading to the activation of Smad1 and Smad5 and subsequent expression of Id proteins. In contrast, low doses of TGF-β1 (0.1 ng/ml) lead to an exclusive activation of ALK5 and phosphorylation of Smad2 and Smad3 that regulate specific target genes including connective tissue growth factor (CTGF). CTGF is rapidly induced by TGF-β1 already 1h after stimulation and reduced by BMP-7 application. Smad1/Smad5 or Id1/2 overexpression reduced the TGF-β1-mediated expression of CTGF. However, although siRNA-mediated knock down of Alk2/3 or Smad1/5 counteracts the BMP-7 effect on basal CTGF expression there was no consistent reversion of the observed BMP-7 effect on TGF-β1-mediated CTGF expression. Moreover, ALK5 inhibition using the SB431542 inhibitor significantly affected CTGF expression only at later time points whereas ERK1/2 pletely abrogated CTGF expression. These findings point towards a regulatory role of BMP-7 that relies on modulation of Mitogen-activated protein kinases rather than mechanisms that are exclusively driven by differential Smad activation.

22099402

[Patent foramen ovale and hypoxaemia with or without elevated right heart pressures].

The prevalence of patent foramen ovale (PFO) is high. As identified at autopsy it is found in approximately 25% of the general population. Anatomically a PFO represents a channel through which unidirectional blood flow from the right to the left atrium may occur. This potential interatrial shunt of unoxygenated venous blood into the oxygenated arterial system may lead to hypoxaemia. Usually right to left shunting across a PFO is transient and without clinical significance. Increased pulmonary arterial pressure may give rise to left-right pressure gradient reversal and right to left shunting across a PFO. High pressure in the right heart chambers, even without pulmonary arterial hypertension, can potentially lead to the reopening of a foramen ovale. In other cases inferior vena cava flow deviation might lead to right to left shunting across a PFO. Right to left shunting without pressure increase inside the right heart chambers is usually transient and even positional and its diagnosis is more difficult.

22099403

[Smokeless tobacco].

Use of smokeless tobacco (ST) (chewing tobacco and snuff) can lead to a number of consequences detrimental to health. ST rapidly delivers high doses of nicotine, which can lead to dependence and is also a source of carcinogenic nitrosamines. Changes usually develop in the mouth area where the ST is most often placed. Non-malignant oral lesions include leuko-oedema, hyperkeratotic lesions of the oral mucosa and localised periodontal disease. Oral premalignant lesions are leukoplakia, erythroplakia, submucosal fibrosis and lichen planus. Betel chewing, with or without tobacco, may increase the incidence of oral cancer. There is conflicting evidence with regard to snuff users about the risk of oral and gastro-oesophageal cancer. ST use is a risk factor for pancreatic cancer and may increase the risk of fatal myocardial infarction and ischemic stroke. During pregnancy, ST is associated with an increase in pre-eclampsia, preterm delivery and stillbirth. Nicotine replacement therapy and bupropion reduce withdrawal symptoms and tobacco craving during ST cessation. However, they have not been shown to help long-term abstinence. Information concerning the potential hazards of ST products should be incorporated into educational programmes to discourage its use and to help users to quit. Smokeless tobacco is not mended to help smoking cessation.

22099404

[What counselling to give to workers occupationally exposed to asbestos?].

When one approaches the issue of the follow-up of workers occupationally exposed to asbestos the first question to resolve is "what counselling to give?" This constitutes an essential first step because it allows people to decide whether or not they wish to accept the proposed follow up programme. The difficulty relates to the idea of exposure to a carcinogen. Facing this question is never easy and generates emotional responses that cannot be ignored. Therefore the content should include elements that allow an understanding of the diseased concerned, the risk (depending on the type of exposure), the benefits and limits of screening, and an awareness of the possible consequences of follow up. The programme should allow enough time for one to one discussion with a professional to consider all aspects. It may be necessary to meet for a second time. This counselling may be given, to subjects over 50 years old, in the framework of either the occupational health or social security services. The counselling of people exposed to asbestos justifies, in itself, a follow up programme and represents its main benefit. It should guarantee the worker's most elementary right: to decide for himself in full knowledge of the facts.

22099405

[Pilot data from the Spirale project -- follow-up of occupational respiratory exposures].

The medical follow-up of individuals who have had occupational exposures to potential respiratory hazards is little known and under-utilised. The Spirale program aims to deliver this intervention effectively to all potential beneficiaries.