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24210787
[Internet and video games among students of Reunion Island in 2010: uses, misuses, perceptions and associated factors].
Describe the uses of Internet and video games and quantify associated problematic uses.
24210788
How to interpret and choose a Bayesian spatial model and a Poisson regression model in the context of describing small area cancer risks variations.
The statistical Bayesian approach is widely used in disease mapping and Poisson regression. Results differ depending on the underlying hypothesis. Our objective is to give prehensive presentation of the tools that can be used to interpret results and choose between the different hypotheses. Data from the Isere cancer registry (France) illustrate this presentation.
24210789
Effect of treatment of vitamin D deficiency and insufficiency during pregnancy on fetal growth indices and maternal weight gain: a randomized clinical trial.
To determine whether treatment of low serum vitamin D in pregnant women improves fetal growth indices.
24210790
Evaluation of serum anti-Mullerian hormone levels to assess the ovarian reserve in women with severe endometriosis.
The aim of this study was to measure anti-Mullerian hormone (AMH) serum levels in women with severe endometriosis, in order to demonstrate the effect of the disease on ovarian reserve.
24210791
Anterior needle-guided mesh in advanced pelvic organ prolapse: apical fixation on sacrospinous ligaments.
To evaluate whether partment mesh implants for pelvic floor reconstruction might be safely and effectively anchored to the sacro-spinous (SS) ligaments instead of the arcus tendineus fascia pelvis (ATFP). The SS ligaments as anchoring structures for centro-apical support mesh fixation are thought to be stronger than the ATFP and we presumed that anterior mesh fixation to the SS ligament might be feasible, safe and effective.
24210792
Spatial organization of xylem cell walls by ROP GTPases and microtubule-associated proteins.
Proper patterning of cellulosic cell walls is critical for cell shaping and differentiation of plant cells. Cortical microtubule arrays regulate the deposition patterns of cellulose microfibrils by controlling the targeting and trajectory of cellulose plexes. Although some microtubule-associated proteins (MAPs) regulate the arrangement of cortical microtubules, knowledge about the overall mechanism governing the spacing of cortical microtubules is still limited. Recent studies reveal that ROP GTPases and MAPs spatially regulate the assembly and disassembly of cortical microtubules in developing xylem cells, in which localized secondary cell walls are deposited. Here, we review recent insights into the regulation of xylem cell wall patterning by cortical microtubules, ROP GTPases, and MAPs.
24210794
Muscular responses to handle perturbation with different glove condition.
Effect of wearing gloves on timely muscle reaction to stabilize handle perturbation was investigated. Thirteen adults gripped a horizontal overhead handle to which an upward force was applied at a random time. Muscle reaction time, integrated EMGs for eight muscles, and handle displacement pared among three glove conditions affecting the coefficient of friction (COF=0.32, 0.50, and 0.74 for the polyester glove, bare hand, and latex glove, respectively). Lower COF increased the integrated EMGs and handle displacement until stabilization of the perturbed handle. The low-friction glove resulted in 16% (p=.01) greater muscular effort and 20% (p=.002) greater handle pared to the high-friction glove. Muscle reaction time was not influenced by glove condition. Cutaneous sensation and reflex eliciting forearm muscle activity appear to play an important role in detecting and responding to the perturbation initially, while the forearm and latissimus dorsi muscles primarily contribute to stabilizing the perturbed pared to other shoulder and upper arm muscles. Therefore, low-friction gloves, cutaneous sensory dysfunction, and weakened forearm and latissimus dorsi muscles may jeopardize persons' ability to stabilize a grip of a handle after perturbation.
24210795
Loading and knee flexion after stroke: Less does not equal more.
It is believed that force feedback can modulate lower extremity extensor activity during gait. The purpose of this research was to determine the role of limb loading on knee extensor excitability during the late stance/early swing phase of gait in persons post-stroke. Ten subjects with chronic hemiparesis post-stroke participated in (1) seated isolated quadriceps reflex testing with ankle loads of 0-0.4Nm/kg and (2) gait analysis on a treadmill with 0%, 20% or 40% body weight support. Muscle reflex responses were recorded from vastus lateralis (VL), rectus femoris (RF), and vastus medialis (VM) during seated testing. Knee kinematics and quadriceps activity during late stance/early swing phase of gait pared across loading conditions. Although isolated loading of the ankle plantarflexors at 0.2Nm/kg reduced VM prolonged response (p=0.04), loading did not alter any other measure of quadriceps excitability (all p>0.08). During gait, the use of BWS did not influence knee kinematics (p=0.18) or muscle activity (all p>0.17) during late stance/early swing phase. This information suggests that load sensed at the ankle has minimal effect on the ipsilateral quadriceps of individuals post-stroke during late stance. It appears that adjusting limb loading during rehabilitation may not be an effective tool to address stiff-knee gait following stroke.
24210793
GM-CSF induces neuroprotective and anti-inflammatory responses in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxicated mice.
Innate and adaptive immune responses can speed nigrostriatal neurodegeneration in Parkinson's disease (PD). We posit that GM-CSF can attenuate such responses. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice, GM-CSF given prior to MPTP protected nigral dopaminergic neurons coincident with altered microglial morphologies and regulatory T cell (Treg) induction. Adoptive transfer of GM-CSF-induced Treg to MPTP mice protected nigral neurons. Gene expression analyses revealed novel immune-based neuronal protection pathways linked to the upregulation of IL-27. The results provide evidence that GM-CSF modulation of immunity could be of clinical benefit for PD.
24210796
Slow expiration reduces sternocleidomastoid activity and increases transversus abdominis and internal oblique muscle activity during abdominal curl-up.
The aim of this study was to investigate the effects of quiet inspiration versus slow expiration on sternocleidomastoid (SCM) and abdominal muscle activity during abdominal curl-up in healthy subjects. Twelve healthy subjects participated in this study. Surface electromyography (EMG) was used to collect activity of bilateral SCM, rectus abdominis (RA), external oblique (EO), and transversus abdominis/internal oblique (TrA/IO) muscles. A paired t-test was used to determine significant differences in the bilateral SCM, RF, EO, and TrA/IO muscles between abdominal curl-up with quiet inspiration and slow expiration. There were significantly lower EMG activity of both SCMs and greater EMG activity of both IOs during abdominal curl-up with slow pared with the EMG activity of both SCMs and IOs during abdominal curl-up with quiet inspiration (p<.05). The results of this study suggest that slow expiration would be mended during abdominal curl-up for reduced SCM activation and selective activation of TrA/IO in healthy pared with those in abdominal curl up with quiet inspiration.
24210797
The latest evidence on target selection in deep brain stimulation for Parkinson's disease.
Deep brain stimulation (DBS) is one of the most promising neuromodulatory techniques to gain momentum over the last 20years, with significant evidence showing the benefit of DBS for Parkinson's disease (PD). However, many questions still exist pertaining to the optimal placement of stimulation contacts. This paper aims to review the latest and most relevant studies evaluating subthalamic nucleus (STN) and globus pallidus interna (GPi) stimulation. Additionally, it aims to shine a light on several of the lesser-known targets with mounting evidence of efficacy. Referenced literature for the main body of the article was gathered from Medline and PubMed databases. Results were limited to "full text", "English language" and publications from 1999 onwards. Case reports were excluded. The current evidence irrefutably demonstrates the benefits of both STN and GPi DBS on Unified Parkinson's Disease Rating Scale (UPDRS) III motor scores, with very similar es seen after 1-2years. Currently, it appears the greatest differences lie in the associated adverse effects. STN DBS was associated with a greater reduction in dopamine replacement therapy, but also appeared to have more negative effects on speech and mood. Meanwhile, in regards to alternative targets, the pedunculopontine nucleus has shown promising improvement in axial symptoms, while the ventral intermediate nucleus has demonstrated significant efficacy at suppressing tremor, and the caudal zona incerta may be superior to the STN and GPi in improving UPDRS-III scores. Due to plexity of Parkinson's disease, an individual disease profile must be determined in a patient-by-patient fashion such that appropriate targets can be selected accordingly.
24210799
Spontaneous cervical intradural disc herniation.
Cervical intradural disc herniation (IDH) is a rare condition with very few case reports in the literature. We report a 64-year-old man who presented with sudden onset neck pain and rapidly progressing weakness in the left upper and lower limb. There was no history of trauma. MRI of the cervical spine showed a C6-C7 disc prolapse, for which he underwent a C6-C7 discectomy and fusion with bone graft through an anterior cervical approach. To our knowledge, all patients with a cervical IDH reported in the literature have a traumatic etiology. To the best of our knowledge, we report the first patient with a spontaneous cervical IDH.
24210798
Changes in serum interleukin-33 levels in patients with acute cerebral infarction.
Inflammation is widely considered to be involved in the pathogenesis of cerebral ischemic injury. The balance between inflammatory and anti-inflammatory factors significantly affects the prognosis of patients with cerebral infarction. Interleukin-33 (IL-33), a newly identified member of the interkeukin-1 superfamily, has been found to play very important roles in the inflammation of several human diseases including asthma, inflammatory bowel disease, and central nervous system inflammation. To our knowledge its role in the pathology of acute cerebral infarction has not yet been reported. In this study, we demonstrated that serum IL-33 levels were significantly increased in patients with acute cerebral pared to control patients without acute cerebral infarction. Furthermore, serum IL-33 levels increased with the infarction volume. Our study suggests that IL-33 may be involved in the pathogenesis and/or progression of acute cerebral infarction.
24210800
Brainstem encephalitis caused by Coxiella burnetii.
Coxiella burnetii is the causative agent of Q fever, which rarely causes neurologic symptoms. We describe a patient who presented with progressive sensory changes, dizziness, and motor weakness. The cerebrospinal fluid revealed pleocytosis, and MRI indicated the presence of a diffuse brain stem lesion. An indirect immunofluorescence test revealed antibodies against C. burnetii. The symptoms improved with antibiotics against C. burnetii. Q fever should be considered as a possible etiology of brainstem encephalitis.
24210801
Panophthalmoplegia and vision loss after cosmetic nasal dorsum injection.
We report a case of unilateral blindness and panophthalmoplegia after hyaluronic acid injection into the dorsum of the nose in a healthy young woman. Microspheres of hyaluronic acid are popular fillers for facial rejuvenation. While ocular side effects from injections in the nose and face have been reported following turbinate injection, rhinoplasty and infraorbital nerve block, ocular side effects from injection into the dorsum of the nose are extremely rare. We presume that the symptoms were due to obstruction of the branches of the ophthalmic artery. Under high injection pressure, the microspheres travelled to the ophthalmic artery and were propelled by the blood flow to the central retinal artery and the anterior and posterior long ciliary arteries, leading to her symptoms. Alternatively, there are several arterio-venous anastomotic channels in the nasal mucosa that aid heat exchange. These may have been the conduit for reflux of the filler into the arterial side of the regional circulation. Physicians must remain aware of plications during cosmetic injections to this region.
24210802
Deep brain stimulator-induced diaphoresis in Parkinson's disease patients.
We report an unusual finding of bilateral facial and corporeal diaphoresis and sensation of heat during deep brain stimulation in two patients. Stimulation of the hypothalamospinal tract located medial to the subthalamic nucleus is likely to be responsible for this side effect.
24210803
Acute inferior homonymous quandrantanopia in a 71-year-old woman.
A 71-year-old woman presented with acute inferior homonymous quadrantanopia initially mimicking acute ischemic stroke. As clinical signs and symptoms progressed to akinetic mutism with myoclonus the diagnosis of the Heidenhain variant of Creutzfeldt-Jakob disease was made. Brain MRI 4 days after symptom onset revealed ribbon-like high signal intensity in the medial occipital cortex.
24210805
Post-surgical thoracic pseudomeningocele causing spinal cord compression.
Pseudomeningoceles are extradural cerebrospinal fluid collections categorized into three groups: traumatic, congenital, and iatrogenic. Iatrogenic pseudomeningoceles occur after durotomy, usually after cervical or lumbar spine surgery. Although many remain asymptomatic, pseudomeningoceles press or herniate the spinal cord and nerve roots. We present a 57-year-old woman who had a thoracic laminectomy and discectomy. Two weeks after surgery, she presented with lower extremity weakness and gait difficulty. Physical examination revealed hyperreflexia and a T11 sensory level. MRI revealed a pressing the thoracic spinal cord. The patient underwent surgical drainage of the cyst. On follow-up, she plete resolution of her symptoms, and MRI did not show a residual lesion. To our knowledge, this is the second documented post-operative pseudomeningocele causing symptomatic spinal pression of the thoracic spine. In this article, a review of the literature is presented, including four reported patients with post-traumatic pseudomeningocele causing myelopathic symptoms and 20 patients with iatrogenic pseudomeningocele that resulted in neurological decline due to herniation pression of neural tissue. Treatment options for these lesions include conservative management, epidural blood patch, lumbar subarachnoid drainage, and lumbo-peritoneal shunt placement. Surgical repair, usually by primary dural closure, remains the definitive treatment modality for iatrogenic symptomatic pseudomeningoceles.
24210804
Successful resection of anterior and anterolateral lesions at the craniovertebral junction using a simple posterolateral approach.
Tumors at the craniovertebral junction (CVJ) often present a challenge due to proximity to vital neurovascular structures. In the last few decades, many authors have plex surgical approaches to access pathologies located anterior or anterolateral to the CVJ with the hopes of reducing morbidity. We propose that the simple posterolateral approach in a semi-sitting position can be used to resect most anterior and anterolateral CVJ tumors safely and effectively. We retrospectively reviewed the clinical series of 10 patients treated by the senior author using the posterolateral suboccipital approach to treat anterior or anterolateral CVJ pathologies. We describe our surgical techniques, es, and present illustrative patients. Gross total resection was achieved in eight patients (80%). Good functional e (Glasgow e Scale 4-5) was obtained in all patients. Preoperative symptoms and deficits were improved (78%) or stable (22%) in all patients. There was one (10%) plication that was cerebrospinal fluid leak requiring reoperation. There was no permanent morbidity or mortality in this series. There were two (20%) plications including deep vein thrombosis and pulmonary embolus. There were three (30%) transient plications, dysphagia in two and dysarthria in one, all of which pletely in early follow-up. The majority of anterior or anterolateral CVJ lesions can be successfully removed using the simple posterolateral approach.
24210806
Brain metastasis from extramammary Paget's disease of the scrotum.
We present to our knowledge the first patient with histopathologically proven brain metastasis from extramammary Paget's disease (EMPD) and discuss the effect of brain radiation therapy for this condition. A 68-year-old man presented to our hospital with headache and gait disturbance. Brain MRI showed multiple enhancing mass lesions, and two large cystic lesions in the left cerebellum. The patient had been diagnosed with scrotal Paget's disease 3 months previously but no further management had been performed due to his refusal. The patient underwent stereotactic aspiration and biopsy of the two large cystic lesions. A histopathological examination revealed that the tumor was a metastatic adenocarcinoma. Immunohistochemical staining revealed that the tumor cells were strongly positive for cytokeratin 7 and moderately positive for carcinoembryonic antigen and gross cystic disease fluid protein 15. These findings were similar to those of his scrotal skin lesions and were consistent with metastatic EMPD. The patient underwent brain radiation therapy with a total radiation dose of 30 Gy in 10 fractions. The patient improved neurologically so as to be self-ambulatory, and a mild improvement in the metastatic tumors was found on follow-up MRI. We had planned systemic chemotherapy, but the patient died of acute respiratory failure 2 months after radiation therapy.
24210807
Endoscopic transnasal resection of ameloblastoma with intracranial extension.
Ameloblastoma is a rare odontogenic tumor with characteristics of epithelial tissue that produces enamel for the developing tooth. This lesion is generally considered benign, but has malignant forms that invade locally and metastasize. We present a 60-year-old man with maxillary ameloblastoma that after multiple recurrences developed intracranial extension with dural involvement of the middle cranial fossa and was treated by endoscopic transnasal resection followed by radiation therapy. Our technique and intraoperative findings are described with a review of the literature on intracranial ameloblastoma. This patient represents a unique account of endoscopic transnasal resection being utilized in the treatment of intracranial extension of ameloblastoma and demonstrates potential for application in similar cases.
24210808
²¹³Bi-anti-EGFR radioimmunoconjugates and X-ray irradiation trigger different cell death pathways in squamous cell carcinoma cells.
Treatment of patients with squamous cell carcinoma of head and neck is hampered by resistance of tumor cells to irradiation. Additional therapies enhancing the effect of X-ray irradiation may be beneficial. Antibodies targeting EGFR have been shown to improve the efficacy of radiation therapy. Therefore, we analyzed cytotoxicity of (213)Bi-anti-EGFR immunoconjugates bination with X-ray irradiation.
24210809
[The role of multimodality imaging in the diagnosis of constrictive pericarditis].
Constrictive pericarditis is a rare heart disease. The diagnosis remains a challenge. In fact, this illness can mimic restrictive cardiomyopathy. Echo-Doppler evaluation helps to establish the diagnosis of constriction; however, this technique is limited in its ability to image the entire pericardium because of its limited acoustic windows by air or bone of thorax. In addition, it is an operator-dependent exploration. Scanner and magnetic resonance imaging provide a large field of view and excellent images, showing the increased pericardial thickness and septal motion abnormalities. This review will consider the emerging role of these imaging modalities in the constrictive pericarditis diagnosis.
24210811
Characterization of betaine aldehyde dehydrogenase (BetB) as an essential virulence factor of Brucella abortus.
The pathogenic mechanisms of Brucellosis used to adapt to the harsh intracellular environment of the host cell are not fully understood. The present study investigated the in vitro and in vivo characteristics of B. abortus betaine aldehyde dehydrogenase (BetB) (Gene Bank ID: 006932) using a betB deletion mutant constructed from virulent B. abortus 544. In test under stress conditions, including osmotic- and acid stress-resistance, the betB mutant had a lower osmotic-resistance than B. abortus wild-type. In addition, the betB mutant showed higher internalization pared to the wild-type strain; however, it also displayed replication failures in HeLa cells and RAW 264.7 macrophages. During pared to the wild-type strain, the betB mutant was more adherent to the host surface and showed enhanced phosphorylation of protein kinases, two processes that promote phagocytic activity, in host cells. During intracellular trafficking, colocalization of B. abortus-containing phagosomes with LAMP-1 was elevated in betB mutant-infected pared to the wild-type cells. In mice, the betB mutant was predominantly cleared from pared to the wild-type strain after 2 weeks post-infection, and the vaccination test with the live betB mutant showed effective protection against challenge infection with the virulent wild-type strain. These findings suggested that the B. abortus betB gene substantially affects the phagocytic pathway in human phagocytes and in host cells in mice. Furthermore, this study highlights the potential use of the B. abortus betB mutant as a live vaccine for the control of brucellosis.
24210810
Reversible overexpression of bace1-cleaved neuregulin-1 N-terminal fragment induces schizophrenia-like phenotypes in mice.
Neuregulin-1 (Nrg1) is a pleiotropic signaling molecule that regulates neural development, and mutation of Nrg1 is a risk factor for schizophrenia. Cleavage of type I β1 Nrg1 isoform by Bace1 releases a secreted N-terminal fragment (Nrg1-ntfβ), which can bind to a cognate ErbB receptor to activate the specific signaling cascade. This study aimed to determine whether increased expression of Nrg1 is beneficial for brain development and functions.
24210812
Genotypes and antibiotic resistance of canine Campylobacter jejuni isolates.
Campylobacter jejuni is the most important cause of bacterial gastroenteritis in humans. It is mensal in many wild and domestic animals, including dogs. Whereas genotypes of human and chicken C. jejuni isolates have been described in some detail, only little information on canine C. jejuni genotypes is available. To gain more information on genotypes of canine C. jejuni and their zoonotic potential, isolates from routine diagnostics of diarrheic dogs as well as isolates of a prevalence study in non-diarrheic dogs were analyzed. Prevalence of thermophilic Campylobacter among non-diarrheic dogs was 6.3% for C. jejuni, 5.9% for Campylobacter upsaliensis and 0.7% for Campylobacter coli. The C. jejuni isolates were genotyped by multi locus sequence typing (MLST) and flaB typing. Resistance to macrolides and quinolones was genetically determined in parallel. Within the 134 genotyped C. jejuni isolates 57 different sequence types (ST) were found. Five STs were previously unrecognized. The mon STs were ST-48 (11.2%), ST-45 (10.5%) and ST-21 (6.0%). Whereas no macrolide resistance was found, 28 isolates (20.9%) were resistant to quinolones. ST-45 was significantly more prevalent in diarrheic than in non-diarrheic dogs. Within mon time frame of isolation 94% of the canine isolates had a ST that was also found in human clinical isolates. In conclusion, prevalence of C. jejuni in Swiss dogs is low but there is a large genetic overlap between dog and human isolates. Given the close contact between human and dogs, the latter should not be ignored as a potential source of human campylobacteriosis.
24210813
Ultrasonic enhancement of battery diffusion.
It has been demonstrated that sonic energy can be harnessed to enhance convection in Galvanic cells during cyclic voltammetry; however, the practical value of this approach is limited due to the lack of open volumes for convection patterns to develop in most batteries. This study evaluates the ability of ultrasonic waves to enhance diffusion in membrane monly used in sandwich-architecture batteries. Studies include the measuring of open-circuit performance curves to interpret performances in terms of reductions in concentration overpotentials. The use of a 40 kHz sonicator bath can consistently increase the voltage of the battery and reduce overpotential losses up to 30%. This work demonstrates and quantifies battery enhancement due to enhanced diffusion made possible with ultrasonic energy.
24210814
Sonication assisted assemblage of exotic polymer supported nanostructured bio-hybrid system and prospective application.
This work was focused on sonication mediated immobilization of porcine pancreatic lipase (PPL) onto poly(ethylene glycol) supported silver-iron oxide hybrid nanoparticles (PEG-Ag/IONPs). Selected process parameters of sonication were optimized using response surface methodology. Sonication assisted assemblage of spherical PEG-Ag/IONPs and consequent evolution of nanorods post PPL immobilization were documented. The efficacy of the reported immobilization strategy was attested by the increased thermostability, storage stability and enhanced activity of the biocatalyst, suggestive of plausible structural modulations post immobilization. mercial prospect of the antibacterial and magnetically recyclable system was vouched by its patibility with mercial detergents for oil de-staining.
24210815
Local functional overconnectivity in posterior brain regions is associated with symptom severity in autism spectrum disorders.
Although growing evidence indicates atypical long-distance connectivity in autism spectrum disorder (ASD), much less is known about local connectivity, despite conjectures that local overconnectivity may be causally involved in the disorder. Using functional connectivity MRI and graph theory, we found that local functional connectivity was atypically increased in adolescents with ASD in temporo-occipital regions bilaterally. Posterior overconnectivity was found to be associated with higher ASD symptom severity, whereas an ASD subsample with low severity showed frontal underconnectivity. The findings suggest links between symptomatology and local connectivity, which vary within the autism spectrum.
24210816
Autoregulation of connexin43 gap junction formation by internally translated isoforms.
During each heartbeat, intercellular electrical coupling via connexin43 (Cx43) gap junctions enables synchronous cardiac contraction. In failing hearts, impaired Cx43 trafficking reduces gap junction coupling, resulting in arrhythmias. Here we report that internal translation within Cx43 (GJA1) mRNA occurs, resulting in truncated isoforms that autoregulate Cx43 trafficking. We find that at least four truncated Cx43 isoforms occur in the human heart, with a 20 kDa isoform predominating. In-frame AUG codons within GJA1 mRNA are the translation initiation sites and their ablation arrests trafficking of full-length Cx43. The 20 kDa isoform is sufficient to rescue this trafficking defect in trans, suggesting it as a trafficking chaperone for Cx43. Limiting cap-dependent translation through inhibition of mTOR enhances truncated isoform expression, increasing Cx43 gap junction size. The results suggest that internal translation is a mechanism of membrane protein autoregulation and a potent target for therapies aimed at restoring normal electrical coupling in diseased hearts.
24210817
SHARPIN regulates uropod detachment in migrating lymphocytes.
SHARPIN-deficient mice display a multiorgan chronic inflammatory phenotype suggestive of altered leukocyte migration. We therefore studied the role of SHARPIN in lymphocyte adhesion, polarization, and migration. We found that SHARPIN localizes to the trailing edges (uropods) of both mouse and human chemokine-activated lymphocytes migrating on intercellular adhesion molecule-1 (ICAM-1), which is one of the major endothelial ligands for migrating leukocytes. SHARPIN-deficient cells adhere better to ICAM-1 and show highly elongated tails when migrating. The increased tail lifetime in SHARPIN-deficient lymphocytes decreases the migration velocity. The adhesion, migration, and uropod defects in SHARPIN-deficient lymphocytes were rescued by reintroducing SHARPIN into the cells. Mechanistically, we show that SHARPIN interacts directly with lymphocyte-function-associated antigen-1 (LFA-1), a leukocyte counterreceptor for ICAM-1, and inhibits the expression of intermediate and high-affinity forms of LFA-1. Thus, SHARPIN controls lymphocyte migration by endogenously maintaining LFA-1 inactive to allow adjustable detachment of the uropods in polarized cells.
24210818
27-Hydroxycholesterol promotes cell-autonomous, ER-positive breast cancer growth.
To date, estrogen is the only known endogenous estrogen receptor (ER) ligand that promotes ER+ breast tumor growth. We report that the cholesterol metabolite 27-hydroxycholesterol (27HC) stimulates MCF-7 cell xenograft growth in mice. More importantly, in ER+ breast cancer patients, 27HC content in normal breast tissue is pared to that in cancer-free controls, and tumor 27HC content is further elevated. Increased tumor 27HC is correlated with diminished expression of CYP7B1, the 27HC metabolizing enzyme, and reduced expression of CYP7B1 in tumors is associated with poorer patient survival. Moreover, 27HC is produced by MCF-7 cells, and it stimulates cell-autonomous, ER-dependent, and GDNF-RET-dependent cell proliferation. Thus, 27HC is a locally modulated, nonaromatized ER ligand that promotes ER+ breast tumor growth.
24210819
Real-time in vivo imaging reveals the ability of monocytes to clear vascular amyloid beta.
Alzheimer's disease (AD) is characterized by the accumulation of amyloid beta (Aβ) that is assumed to result from impaired elimination of this neurotoxic peptide. Most patients with AD also exhibit cerebral amyloid angiopathy, which consists of Aβ deposition within the cerebral vasculature. The contribution of monocytes in AD has so far been limited to macrophage precursors. In this study, we aimed to investigate whether circulating monocytes could play a role in the elimination of Aβ. With live intravital two-photon microscopy, we demonstrate that patrolling monocytes are attracted to and crawl onto the luminal walls of Aβ-positive veins, but not on Aβ-positive arteries or Aβ-free blood vessels. Additionally, we report the presence of crawling monocytes carrying Aβ in veins and their ability to circulate back into the bloodstream. Selective removal of Ly6C(lo) monocytes in APP/PS1 mice induced a significant increase of Aβ load in the cortex and hippocampus. These data uncover the ability of Ly6C(lo) monocytes to naturally target and eliminate Aβ within the lumen of veins and constitute a potential therapeutic target in AD.
24210820
SIRT7 represses Myc activity to suppress ER stress and prevent fatty liver disease.
Nonalcoholic fatty liver disease is the mon chronic liver disorder in developed countries. Its pathogenesis is poorly understood, and therapeutic options are limited. Here, we show that SIRT7, an NAD(+)-dependent H3K18Ac deacetylase, functions at chromatin to suppress ER stress and prevent the development of fatty liver disease. SIRT7 is induced upon ER stress and is stabilized at the promoters of ribosomal proteins through its interaction with the transcription factor Myc to silence gene expression and to relieve ER stress. SIRT7-deficient mice develop chronic hepatosteatosis resembling human fatty liver disease. Myc inactivation or pharmacological suppression of ER stress alleviates fatty liver caused by SIRT7 deficiency. Importantly, SIRT7 suppresses ER stress and reverts the fatty liver disease in diet-induced obese mice. Our study identifies SIRT7 as a cofactor of Myc for transcriptional repression and delineates a druggable regulatory branch of the ER stress response that prevents and reverts fatty liver disease.
24210821
Brain hyperconnectivity in children with autism and its links to social deficits.
Autism spectrum disorder (ASD), a neurodevelopmental disorder affecting nearly 1 in 88 children, is thought to result from aberrant brain connectivity. Remarkably, there have been no systematic attempts to characterize whole-brain connectivity in children with ASD. Here, we use neuroimaging to show that there are more instances of greater functional connectivity in the brains of children with ASD parison to those of typically developing children. Hyperconnectivity in ASD was observed at the whole-brain and subsystems levels, across long- and short-range connections, and was associated with higher levels of fluctuations in regional brain signals. Brain hyperconnectivity predicted symptom severity in ASD, such that children with greater functional connectivity exhibited more severe social deficits. We replicated these findings in two additional independent cohorts, demonstrating again that at earlier ages, the brain of children with ASD is largely functionally hyperconnected in ways that contribute to social dysfunction. Our findings provide unique insights into brain mechanisms underlying childhood autism.
24210822
Specificity of monosynaptic sensory-motor connections imposed by repellent Sema3E-PlexinD1 signaling.
In mammalian spinal cord, group Ia proprioceptive afferents form selective monosynaptic connections with a select group of motor pool targets. The extent to which sensory recognition of motor neurons contributes to the selectivity of sensory-motor connections remains unclear. We show here that proprioceptive sensory afferents that express PlexinD1 avoid forming monosynaptic connections with neurons in Sema3E(+) motor pools yet are able to form direct connections with neurons in Sema3E(off) motor pools. Anatomical and electrophysiological analysis of mice in which Sema3E-PlexinD1 signaling has been deregulated or inactivated genetically reveals that repellent signaling underlies aspects of the specificity of monosynaptic sensory-motor connectivity in these reflex arcs. A semaphorin-based system of motor neuron recognition and repulsion therefore contributes to the formation of specific sensory-motor connections in mammalian spinal cord.
24210823
DUB-resistant ubiquitin to survey ubiquitination switches in mammalian cells.
The ubiquitin-modification status of proteins in cells is highly dynamic and maintained by specific ligation machineries (E3 ligases) that tag proteins with ubiquitin or by deubiquitinating enzymes (DUBs) that remove the ubiquitin tag. The development of tools that offset this balance is critical in characterizing signaling pathways that utilize such ubiquitination switches. Herein, we generated a DUB-resistant ubiquitin mutant that is recalcitrant to cleavage by various families of DUBs both in vitro and in mammalian cells. As a proof-of-principle experiment, ectopic expression of the uncleavable ubiquitin stabilized monoubiquitinated PCNA in the absence of DNA damage and also revealed a defect in the clearance of the DNA damage response at unprotected telomeres. Importantly, a proteomic survey using the uncleavable ubiquitin identified ubiquitinated substrates, validating the DUB-resistant ubiquitin expression system as a valuable tool for interrogating cell signaling pathways.
24210824
Changes in cellular mRNA stability, splicing, and polyadenylation through HuR protein sequestration by a cytoplasmic RNA virus.
The impact of RNA viruses on the posttranscriptional regulation of cellular gene expression is unclear. Sindbis virus causes a dramatic relocalization of the cellular HuR protein from the nucleus to the cytoplasm in infected cells. This is to the result of the expression of large amounts of viral RNAs that contain high-affinity HuR binding sites in their 3' UTRs effectively serving as a sponge for the HuR protein. Sequestration of HuR by Sindbis virus is associated with destabilization of cellular mRNAs that normally bind HuR and rely on it to regulate their expression. Furthermore, significant changes can be observed in nuclear alternative polyadenylation and splicing events on cellular pre-mRNAs as a result of sequestration of HuR protein by the 3' UTR of transcripts of this cytoplasmic RNA virus. These studies suggest a molecular mechanism of virus-host interaction that probably has a significant impact on virus replication, cytopathology, and pathogenesis.
24210826
High-frequency promoter firing links THO complex function to heavy chromatin formation.
The plex is involved in transcription, genome stability, and messenger ribonucleoprotein (mRNP) formation, but its precise molecular function remains enigmatic. Under heat shock conditions, THO mutants accumulate large plexes that alter the chromatin density of target genes (heavy chromatin), defining a specific biochemical facet of THO function and a powerful tool of analysis. Here, we show that heavy chromatin distribution is dictated by gene boundaries and that the gene promoter is necessary and sufficient to convey THO sensitivity in these conditions. Single-molecule fluorescence in situ hybridization measurements show that heavy chromatin formation correlates with an unusually high firing pace of the promoter with more than 20 transcription events per minute. Heavy chromatin formation closely follows the modulation of promoter firing and strongly correlates with polymerase occupancy genome wide. We propose that the plex is required for tuning the dynamic of gene-nuclear pore association and mRNP release to the same high pace of transcription initiation.
24210825
High-resolution replication profiles define the stochastic nature of genome replication initiation and termination.
Eukaryotic genome replication is stochastic, and each cell uses a different cohort of replication origins. We demonstrate that interpreting high-resolution Saccharomyces cerevisiae genome replication data with a mathematical model allows quantification of the stochastic nature of genome replication, including the efficiency of each origin and the distribution of termination events. Single-cell measurements support the inferred values for stochastic origin activation time. A strain, in which three origins were inactivated, confirmed that the distribution of termination events is primarily dictated by the stochastic activation time of origins. Cell-to-cell variability in origin activity ensures that termination events are widely distributed across virtually the whole genome. We propose that the heterogeneity in origin usage contributes to genome stability by limiting potentially deleterious events from accumulating at particular loci.
24210828
The effects of long-term therapy with proton pump inhibitors on meal stimulated gastrin.
Dyspepsia develops in healthy volunteers after withdrawal of proton-pump inhibitors. This phenomenon, attributed to rebound acid hypersecretion, is thought to be mediated by reflex hypergastrinemia.
24210827
Roles of exonucleases and translesion synthesis DNA polymerases during mitotic gap repair in yeast.
Transformation-based gap-repair assays have long been used to model the repair of mitotic double-strand breaks (DSBs) by homologous bination in yeast. In the current study, we examine genetic requirements of two key processes involved in DSB repair: (1) the processive 5'-end resection that is required to efficiently engage a repair template and (2) the filling of resected ends by DNA polymerases. The specific gap-repair assay used allows repair events resolved as crossover versus noncrossover products to be distinguished, as well as the extent of heteroduplex DNA formed during bination to be measured. To examine end resection, the efficiency and e of gap repair were monitored in the absence of the Exo1 exonuclease and the Sgs1 helicase. We found that either Exo1 or Sgs1 presence is sufficient to inhibit gap-repair efficiency over 10-fold, consistent with resection-mediated destruction of the introduced plasmid. In terms of DNA polymerase requirements for gap repair, we focused specifically on potential roles of the Pol ζ and Pol η translesion synthesis DNA polymerases. We found that both Pol ζ and Pol η are necessary for efficient gap repair and that each functions independently of the other. These polymerases may be involved either in the initiation of DNA synthesis from the an invading end, or in a gap-filling process that is required plete bination.
24210829
Clinicopathologic characteristics and outcomes of penile cancer treated at tertiary care centers in the Western United States.
This article reports on the experience with penile squamous cell carcinoma (PSCC) in a unique multiethnic patient population from Los Angeles, California, with regard to treatments rendered and clinical es.
24210830
Repair of posterior mitral valve prolapse with a novel leaflet plication clip in an animal model.
Recently, there has been increased interest in minimally invasive mitral valve prolapse repair techniques; however, these techniques have limitations. A new technique was developed for treating mitral valve prolapse that uses a novel leaflet plication clip to selectively plicate the prolapsed leaflet segment. The clip's efficacy was tested in an animal model.
24210831
Dexamethasone levels predict cortisol response after infant cardiopulmonary bypass.
We sought to evaluate whether there is variability in blood dexamethasone levels after a standard 1 mg/kg dose of dexamethasone administered before infant cardiopulmonary bypass. We hypothesized that postoperative dexamethasone drug levels are highly variable, and that the infant stress response is related inversely to the amount of dexamethasone measured in the blood.
24210834
Comparing robot-assisted thoracic surgical lobectomy with conventional video-assisted thoracic surgical lobectomy and wedge resection: results from a multihospital database (Premier).
Video-assisted thoracic surgical (VATS) lobectomies and wedge resections result in less morbidity and shorter length of stay than resections via thoracotomy. The impact of robot-assisted thoracic surgical (RATS) lobectomy on clinical and economic es has not been examined. This pared hospital costs and clinical es for VATS lobectomies and wedge resections versus RATS.
24210835
Genotype-oropharyngeal phenotype correlation in Mexican patients with dystrophic epidermolysis bullosa.
Previous investigations have attempted to correlate the genotype with the cutaneous phenotype in patients with epidermolysis bullosa (EB), but never with the oropharyngeal phenotype. Seventeen dystrophic EB (DEB) patients were genotyped for COL7A1 gene mutations and divided into five distinct groups. Oropharyngeal disease severity was assessed with the Epidermolysis Bullosa Oropharyngeal Severity (EBOS) score by an oral medicine specialist. The genotype-phenotype correlation was calculated by Kruskal-Wallis analysis of variance using the Mann-Whitney test, applying the Bonferroni correction. The most severe oropharyngeal phenotype was found in the group with the 2470insG/3948insT mutation, with a mean disease severity score of 18.50 ± 2.12; the mildest was found in the 6862del16 mutation group, with a mean disease severity score of 0.57 ± 1.13. The most significant difference in median score was found in the total score (P = 0.009), followed by tongue (P = 0.02) and upper lip (P = 0.021), but no correlation was found between disease severity and the groups (P>0.005, after Bonferroni correction). parisons among the five different genotypic groups revealed no statistically significant genotype-oropharyngeal phenotype correlation; it was not possible to establish which group was more severe, or to associate a specific mutation to a specific oropharyngeal phenotype.
24210838
What is the value of historical fidelity in restoration?
The following considers the role of historical fidelity in habitat reconstruction efforts. To what extent should habitat reconstruction be guided by the goal of recreating some past state of a damaged ecosystem? I consider Sarkar's "replacement argument," which holds that, in most habitat reconstruction efforts, there is little justification for appealing to historical fidelity. I argue that Sarkar does not provide adequate grounds for deprecating historical fidelity relative to other natural values such as biodiversity or wild nature.
24210839
Effects of albumin and synthetic polypeptide-coated oxygenators on IL-1, IL-2, IL-6, and IL-10 in open heart surgery.
In this study, we have tried to demonstrate the effects of coating style used in oxygenators on various hematologic and clinical parameters.
24210836
Does acute passive stretching increase muscle length in children with cerebral palsy?
Children with spastic cerebral palsy experience increased muscle stiffness and reduced muscle length, which may prevent elongation of the muscle during stretch. Stretching performed either by the clinician, or children themselves is used as a treatment modality to increase/maintain joint range of motion. It is not clear whether the associated increases in muscle-tendon unit length are due to increases in muscle or tendon length. The purpose was to determine whether alterations in ankle range of motion in response to acute stretching were panied by increases in muscle length, and whether any effects would be dependent upon stretch technique.
24210837
Relationship of plasma cytokines and clinical biomarkers to memory performance in HIV.
Chronic systemic immune activation and inflammatory processes have been linked to brain dysfunction in medically stable HIV-infected people. We investigated the association between verbal memory performance and plasma concentrations of 13 cytokines measured using multiplexed bead array immunoassay in 74 HIV-seropositive individuals and 50 HIV-seronegative controls. Memory performance was positively related to levels of IL-8 and IFN-γ, and negatively related to IL-10 and IL-18 and to hepatitis C infection. Memory performance was not significantly related to HIV disease markers. The results indicate the importance of systemic immune and inflammatory markers to neurocognitive function in chronic and stable HIV disease.
24210840
Behavioral compliance for dynamic versus static signs in an immersive virtual environment.
This study used an immersive virtual environment (IVE) to examine how dynamic features in signage affect pliance during a work-related task and an emergency egress. Ninety participants performed a work-related task followed by an emergency egress. Compliance with uncued and cued safety signs was assessed prior to an explosion/fire involving egress with exit signs. Although dynamic presentation produced the pliance, the difference between dynamic and static presentation was only statistically significant for uncued signs. Uncued signs, both static and dynamic, were effective in changing pared to no/minimal signs. Findings are explained based on sign salience and on task differences. If signs must capture attention while individuals are attending to other tasks, salient (e.g., dynamic) signs are useful in pliance. This study demonstrates the potential for IVEs to serve as a useful tool in pliance research.
24210842
A study to promote breast feeding in the Helsinki Metropolitan area in Finland.
the aim of this study was to assess the impact of providing intensified support for breast feeding during the perinatal period.
24210843
Computer-assisted training of phoneme-grapheme correspondence for children who are deaf and hard of hearing: effects on phonological processing skills.
Examine deaf and hard of hearing (DHH) children's phonological processing skills in relation to a reference group of children with normal hearing (NH) at two baselines pre intervention. Study the effects puter-assisted phoneme-grapheme correspondence training in the children. Specifically analyze possible effects on DHH children's phonological processing skills.
24210844
A new device for treatment of persistent otitis media with effusion.
Most children suffer from otitis media with effusion (OME) before starting school. Insertion of grommets into the eardrum for treatment of OME is one of the mon operations performed in childhood. The efficiency pliance of treatment with a new non-invasive device was evaluated in children with bilateral OME with disease duration of at least 3 months.
24210845
Streptococcal superantigens: categorization and clinical associations.
Superantigens are key virulence factors in the immunopathogenesis of invasive disease caused by group A streptococcus. These protein exotoxins have also been associated with severe group C and group G streptococcal infections. A number of novel streptococcal superantigens have recently been described with some resulting confusion in their classification. In addition to clarifying the nomenclature of streptococcal superantigens and proposing guidelines for their categorization, this review summarizes the evidence supporting their involvement in various clinical diseases including acute rheumatic fever.
24210847
Stump infections after major lower-limb amputation: a 10-year retrospective study.
There is little published data on the diagnostic and therapeutic management of lower-limb stump infections (excluding toe and forefoot amputations).
24210848
Evaluation of a subject-specific finite-element model of the equine metacarpophalangeal joint under physiological load.
The equine metacarpophalangeal (MCP) joint is frequently injured, especially by racehorses in training. Most injuries result from repetitive loading of the subchondral bone and articular cartilage rather than from acute events. The likelihood of injury is multi-factorial but the magnitude of mechanical loading and the number of loading cycles are believed to play an important role. Therefore, an important step in understanding injury is to determine the distribution of load across the articular surface during normal otion. A subject-specific finite-element model of the MCP joint was developed (including deformable cartilage, elastic ligaments, muscle forces and rigid representations of bone), evaluated against measurements obtained from cadaver experiments, and then loaded using data from gait experiments. The sensitivity of the model to force inputs, cartilage stiffness, and cartilage geometry was studied. The FE model predicted MCP joint torque and sesamoid bone flexion angles within 5% of experimental measurements. Muscle-tendon forces, joint loads and cartilage stresses all increased as otion speed increased from walking to trotting and finally cantering. Perturbations to muscle-tendon forces resulted in small changes in articular cartilage stresses, whereas variations in joint torque, cartilage geometry and stiffness produced much larger effects. Non-subject-specific cartilage geometry changed the magnitude and distribution of pressure and the von Mises stress markedly. The mean and peak cartilage stresses generally increased with an increase in cartilage stiffness. Areas of peak stress correlated qualitatively with sites mon injury, suggesting that further modelling work may elucidate the types of loading that precede joint injury and may assist in the development of techniques for injury mitigation.
24210849
Murine patellar tendon biomechanical properties and regional strain patterns during natural tendon-to-bone healing after acute injury.
Tendon-to-bone healing following acute injury is generally poor and often fails to restore normal tendon biomechanical properties. In recent years, the murine patellar tendon (PT) has e an important model system for studying tendon healing and repair due to its genetic tractability and accessible location within the knee. However, the mechanical properties of native murine PT, specifically the regional differences in tissue strains during loading, and the biomechanical es of natural PT-to-bone healing have not been well characterized. Thus, in this study, we analyzed the global biomechanical properties and regional strain patterns of both normal and naturally healing murine PT at three time points (2, 5, and 8 weeks) following acute surgical rupture of the tibial enthesis. Normal murine PT exhibited distinct regional variations in tissue strain, with the insertion region experiencing approximately 2.5 times greater strain than the midsubstance at failure (10.80±2.52% vs. 4.11±1.40%; mean±SEM). Injured tendons showed reduced structural (ultimate load and linear stiffness) and material (ultimate stress and linear modulus) pared to both normal and contralateral sham-operated tendons at all healing time points. Injured tendons also displayed increased local strain in the insertion pared to contralateral shams at both physiologic and failure load levels. 93.3% of injured tendons failed at the tibial pared to only 60% and 66.7% of normal and sham tendons, respectively. These results indicate that 8 weeks of natural tendon-to-bone healing does not restore normal biomechanical function to the murine PT following injury.
24210850
Walking at the preferred stride frequency maximizes local dynamic stability of knee motion.
Healthy humans display a preference for walking at a stride frequency dependent on the inertial properties of their legs. Walking at preferred stride frequency (PSF) is predicted to maximize local dynamic stability, whereby sensitivity to intrinsic perturbations arising from natural variability inherent in biological motion is minimized. Previous studies testing this prediction have employed different variability measures, but none have directly quantified local dynamic stability puting maximum finite-time Lyapunov exponent (λ(Max)), which quantifies the rate of divergence of nearby trajectories in state space. Here, ten healthy adults walked 45 m overground while sagittal motion of both knees was recorded via electrogoniometers. An auditory metronome prescribed 7 different frequencies relative to each individual's PSF (PSF; ±5, ±10, ±15 strides/min). Stride frequencies were performed under both freely adopted speed (FS) and controlled speed (CS: set at the speed of PSF trials) conditions. Local dynamic stability was maximal (λ(Max) was minimal) at the PSF, ing less stable for higher and lower stride frequencies. This occurred under both FS and CS conditions, although controlling speed further reduced local dynamic stability at non-preferred stride frequencies. In contrast, measures of variability revealed effects of stride frequency and speed conditions that were distinct from λ(Max). In particular, movement puted by approximate entropy (ApEn) increased for slower walking speeds, appearing to depend on speed rather than stride frequency. The cadence freely adopted by humans has the benefit of maximizing local dynamic stability, which can be interpreted as humans tuning to their resonant frequency of walking.
24210851
Pediatric bed fall computer simulation model: parametric sensitivity analysis.
Falls from beds and other household furniture mon scenarios that may result in injury and may also be stated to conceal child abuse. Knowledge of the biomechanics associated with short-distance falls may aid clinicians in distinguishing between abusive and accidental injuries. In this study, a validated bed puter simulation model of an anthropomorphic test device representing a 12-month-old child was used to investigate the effect of altering fall environment parameters (fall height, impact surface stiffness, initial force used to initiate the fall) and child surrogate parameters (overall mass, head stiffness, neck stiffness, stiffness for other body segments) on fall dynamics and es related to injury potential. The sensitivity of head and neck injury e measures to model parameters was determined. Parameters associated with the greatest sensitivity values (fall height, initiating force, and surrogate mass) altered fall dynamics and impact orientation. This suggests that fall dynamics and impact orientation play a key role in head and neck injury potential. With the exception of surrogate mass, injury e measures tended to be more sensitive to changes in environmental parameters (bed height, impact surface stiffness, initiating force) than surrogate parameters (head stiffness, neck stiffness, body segment stiffness).
24210852
Quantification of finger joint loadings using musculoskeletal modelling clarifies mechanical risk factors of hand osteoarthritis.
Owing to limited quantitative data related to the loadings (forces and pressures) acting upon finger joints, several clinical observations regarding mechanical risk factors of hand osteoarthritis remain misunderstood. To improve the knowledge of this pathology, the present study used musculoskeletal modelling to quantify the forces and pressures acting upon hand joints during two grasping tasks. Kinematic and grip force data were recorded during both a pinch and a power grip tasks. Three-dimensional magnetic resonance imaging measurements were conducted to quantify joint contact areas. Using these datasets as input, a musculoskeletal model of the hand and wrist, including twenty-three degrees of freedom and forty-two muscles, has been developed to estimate joint forces and joint pressures. pared with the power grip task, the pinch grip task resulted in two to eight times higher joint loadings whereas the grip forces exerted on each finger were twice lower. For both tasks, joint forces and pressures increased along a disto-proximal direction for each finger. The quantitative dataset provided by the present hand model clarified two clinical observations about osteoarthritis development which were not fully understood, i.e., the strong risk associated to pinch grip tasks and the high frequency of thumb-base osteoarthritis.
24210854
Effect of swirling inlet condition on the flow field in a stenosed arterial vessel model.
Blood flow in an artery is closely related to atherosclerosis progression. Hemodynamic environments influence platelet activation, aggregation, and rupture of atherosclerotic plaque. The existence of swirling ponents in an artery is frequently observed under in vivo conditions. However, the fluid-dynamic roles of spiral flow are not fully understood to date. In this study, the spiral blood flow effect in an axisymmetric stenosis model was experimentally investigated using particle image velocimetry velocity field measurement technique and streakline flow visualization. Spiral inserts with two different helical pitches (10D and 10/3D) were installed upstream of the stenosis to induce swirling flows. Results show that the spiral flow significantly reduces the length of recirculation flow and provokes early breakout of turbulent transition, but variation of swirling intensity does not induce significant changes of turbulence intensity. The present results about the spiral flow effects through the stenosis will contribute in achieving better understanding of the hemodynamic characteristics of atherosclerosis and in discovering better diagnosis procedures and clinical treatments.
24210853
Molecular markers of programmed cell death in donor hearts before transplantation.
In this study we investigate whether pro-apoptotic, pro-inflammatory and other early signaling markers indicative of increased propensity for cell death processes were evident in human donor heart allografts immediately before transplantation, and whether there is an association with primary graft failure.
24210855
Bile and liver metallothionein behavior in copper-exposed fish.
The present study analyzed metallothionein (MT) excretion from liver to bile in Nile Tilapia (Oreochromis niloticus) exposed to sub-lethal copper concentrations (2mgL(-1)) in a laboratory setting. MTs in liver and bile were quantified by spectrophotometry after thermal incubation and MT metal-binding profiles were characterized by size exclusion high performance liquid chromatography coupled to ICP-MS (SEC-HPLC-ICP-MS). Results show that liver MT is present in approximately 250-fold higher concentrations than bile MT in non-exposed fish. Differences between the MT profiles from the control and exposed group were observed for both matrices, indicating differential metal-binding behavior paring liver and bile MT. This is novel data regarding intra-organ parisons, since differences between organs are usually present only with regard to quantification, not metal-binding behavior. Bile MT showed statistically significant differences between the control and exposed group, while the same did not occur with liver MT. This indicates that MTs synthesized in the liver accumulate more slowly than MTs excreted from liver to bile, since the same fish presented significantly higher MT levels in liver pared to bile. We postulate that bile, although excreted in the intestine and partially reabsorbed by the same returning to the liver, may also release MT-bound metals more rapidly and efficiently, which may indicate an efficient detoxification route. Thus, we propose that the analysis of bile MTs to observe recent metal exposure may be more adequate than the analysis of liver MTs, since organism responses to metals are more quickly observed in bile, although further studies are necessary.
24210856
Ultrasound thermal mapping based on a hybrid method combining physical and statistical models.
Non-invasive temperature measurement of tissues deep inside the body has great potential for clinical applications, such as temperature monitoring during thermal therapy and early diagnosis of diseases. We developed a novel method for both temperature estimation and thermal mapping that uses ultrasound B-mode radiofrequency data. The proposed method is a hybrid bines elements of physical and statistical models to achieve higher precision and resolution of temperature variations and distribution. We propose a bined index (CI) bines the echo shift differential and signal intensity difference with a weighting factor relative to the distance from the heat source. In vitro experiments verified that bined index has a strong linear relationship with temperature variation and can be used to effectively estimate temperature with an average relative error <5%. This algorithm provides an alternative for imaging guidance-based techniques during thermal therapy and could easily be integrated into existing ultrasound systems.
24210857
3-D high-frequency ultrasound backscatter analysis of human articular cartilage.
High-frequency ultrasound is a promising method for non-invasive characterization of cartilage degeneration. Surface reflection and integrated spectral parameters are often used. In the work described here, human cartilage samples with varying degrees of degeneration were measured using a 40-MHz transducer. Backscatter signals originating from the superficial and transitional zones of cartilage were analyzed using amplitude, spectral and envelope statistical parameters and related to degenerative changes of the matrix given by the Mankin score. The results indicate an increased sensitivity of spectral slope and envelope statistical parameters to early matrix pared with conventional amplitude parameters. Furthermore, moderate correlations of chondrocyte number with backscatter amplitude and envelope statistics were observed, suggesting that at high frequencies, cells are one important scattering source in cartilage. An application of spectral and envelope statistical parameters to intra-articular ultrasound arthroscopy is conceivable and could improve the diagnostic potential of these examinations. Future studies are necessary to clarify the contributions of chondrocytes, extracellular matrix and collagen content to ultrasound backscatter to further improve the diagnostic potential of ultrasound for cartilage assessment.
24210858
Muscle ultrasound quantifies segmental neuromuscular outcome in pediatric myelomeningocele.
In pediatric spina bifida aperta (SBA), non-invasive assessment of neuromuscular integrity by muscle ultrasound density (MUD) could provide important information about the clinical condition. We therefore aimed to determine the association between pediatric SBA MUD and segmental neurologic function. We included 23 children (age range: 1-18 y) with SBA with L4-5 lesions, and we associated SBA MUD with control values and segmental neuromuscular function. Results revealed that MUD es in the lower extremities: (i) are independent of age, (ii) exceed control values, (iii) differ intra-individually (i.e., between the left and right sides in the same individual) in association with segmental neuromuscular function. We concluded that SBA leg MUD can quantify the segmental neuromuscular condition throughout childhood.
24210859
Ultra-high frame rate tissue Doppler imaging.
We describe a new tissue Doppler imaging (TDI) method, ultra-high frame rate tissue Doppler imaging (UFR-TDI). With two broad transmit beams covering only the ventricular walls, we achieve 1200 frames/s in a four-chamber apical view. We examined 10 healthy volunteers to study the feasibility of this method. Ultra-high-frame-rate TDI provided peak annular velocities and time to peak S' intervals in good agreement with those measured with conventional TDI. Moreover, UFR-TDI provided additional information in early and late systole: In all subjects, the method was able to separate the timing of electrical activation, start of mechanical contraction, mitral valve closure and start of ejection. The earliest mechanical activation was seen before mitral valve closure. The method was also able to measure the propagation speed of the mechanical wave created by aortic valve closure.
24210860
Comparison of diffuse optical tomography, ultrasound elastography and mammography in the diagnosis of breast tumors.
Previous studies have reported the usefulness of diffuse optical tomography (DOT), ultrasound elastography (UE) and mammography in differentiating breast tumors. This study was aimed at evaluating paring DOT, UE and mammography with respect to their diagnostic performance in differentiating benign and malignant breast tumors. Of the 67 tumors, 45 were histopathologically benign, and 22 were malignant. UE was the most specific (93.33%) of the three diagnostics modalities. DOT and UE were both more accurate (80.60% and 89.55%, respectively) than mammography (63.08%). UE + mammography (93.33% and 91.04%) and DOT + mammography (77.78% and 82.09%) exhibited higher specificity and accuracy, respectively, than mammography alone (57.78% and 63.08%). Receiver operating characteristic (ROC) curves were constructed to assess the performance of the modalities. In conclusion, UE and DOT were superior to conventional mammography in terms of both specificity and accuracy. DOT and UE improve the specificity and accuracy of breast cancer diagnosis, bining the two modalities improves the diagnostic value.
24210861
Shear wave elastography assessment of carotid plaque stiffness: in vitro reproducibility study.
This study assessed inter- and intra-observer reproducibility of shear wave elastography (SWE) measurements in vessel phantoms simulating soft and hard carotid plaque under steady and pulsatile flow conditions. Supersonic SWE was used to acquire cine-loop data and quantify Young's modulus in cryogel vessel phantoms. Data were acquired by two observers, each performing three repeat measurements. Mean Young's modulus was quantified within 2-mm regions of interest averaged across five frames and, depending on vessel model and observer, ranged from 28 to 240 kPa. The mean inter-frame coefficient of variation (CV) was 0.13 (range: 0.07-0.18) for observer 1 and 0.14 (range: 0.12-0.16) for observer 2, with mean intra-class correlation coefficients (ICCs) of 0.84 and 0.83, respectively. The mean inter-operator CV was 0.13 (range: 0.08-0.20), with a mean ICC of 0.76 (range: 0.69-0.82). Our findings indicate that SWE can quantify Young's modulus of carotid plaque phantoms with good reproducibility, even in the presence of pulsatile flow.
24210862
Transverse ultrasound assessment of median nerve deformation and displacement in the human carpal tunnel during wrist movements.
The symptoms of carpal tunnel syndrome, pression neuropathy of the median nerve at the wrist, are aggravated by wrist motion, but the effect of these motions on median nerve motion are unknown. To better understand the biomechanics of the abnormal nerve, it is first necessary to understand normal nerve movement. The purpose of this study was to evaluate the deformation and displacement of the normal median nerve at the proximal carpal tunnel level on transverse ultrasound images during different wrist movements, to have a baseline parison with abnormal movements. Dynamic ultrasound images of both wrists of 10 asymptomatic volunteers were obtained during wrist maximal flexion, extension and ulnar deviation. To simplify the analysis, the initial and final shape and position of the median nerve were measured and analyzed. The circularity of the median nerve was significantly increased and the aspect ratio and perimeter were significantly decreased in the final pared with the first image during wrist flexion with finger extension, wrist flexion with finger flexion and wrist ulnar deviation with finger extension (p < 0.01). There were significant differences in median nerve displacement vector between finger flexion, wrist flexion with finger extension and wrist ulnar deviation with finger extension (all p's < 0.001). The mean amplitudes of median nerve motion in wrist flexion with finger extension (2.36 ± 0.79 normalized units [NU]), wrist flexion with finger flexion (2.46 ± 0.84 NU) and wrist ulnar deviation with finger extension (2.86 ± 0.51 NU) were higher than those in finger flexion (0.82 ± 0.33 NU), wrist extension with finger extension (0.77 ± 0.46 NU) and wrist extension with finger flexion (0.81 ± 0.58 NU) (p < 0.0001). In the normal carpal tunnel, wrist flexion and ulnar deviation could induce significant transverse displacement and deformation of the median nerve.
24210863
Visualizing tendon elasticity in an ex vivo partial tear model.
Supersonic shear imaging (SSI) is evaluated as a means of visualizing changes in regional tendon elasticity caused by partial tears in a porcine model. Thirty digital flexor tendons were cut to 25% (n = 10), 50% (n = 10) and 75% (n = 10) of the tendon thickness along the deep surface. Tendon elasticity was mapped left of, centered on and right of the tear site before and after tearing from 0% to 2% strain. Shear wave speed increased at 1% (p < 0.05) and 2% (p < 0.001) strain for all regions. Deep surface shear wave speed decreased in the 25%, 50% and 75% tears (p < 0.05 and p < 0.001). Computational tendon tear models were also created to investigate regional changes in strain resulting from a tear. In putational models, strain on the deep surface decreased progressively with increasing tear size. Visualization of tendon shear wave speed was achieved in normal and partially torn tendons, indicating the potential of SSI to add tendon shear wave speed to traditional morphologic assessment of partial tears, which may improve assessment of tendon health.
24210864
A novel microfluidic chip for assessing dynamic adhesion behavior of cell-targeting microbubbles.
The primary aim of this study was to develop a microfluidic chip to study the dynamic adhesion behavior of cell-targeted microbubbles. The microfluidic device posed of polydimethylsiloxane and is fabricated using the soft lithography technique. Each chamber of the microfluidic prises eight U-shaped microsieves, by which various flow velocity distributions are generated. LyP-1-conjugated microbubbles were prepared by coating the surface of the phospholipid shell of microbubbles with LyP-1 peptides via biotin-avidin linkage. Under static conditions, the resulting targeted microbubbles are able to bind onto the surface of cells on incubation with breast cancer cells. Under dynamic fluid conditions, the cell targeting efficiency of the microbubbles was assessed at various flow velocity distributions in a chamber. Accumulation of targeted microbubbles was strongly influenced by flow velocity. Better retention of targeted microbubbles on cell surfaces was achieved at low mean flow velocities (<0.03 cm/s), in agreement with puter simulation results. In conclusion, our results indicate that the microfluidic system is a useful platform for studying the microbubble-cell adhesive interaction.
24210865
Doppler vortography: a color Doppler approach to quantification of intraventricular blood flow vortices.
We propose a new approach to quantification of intracardiac vorticity based on conventional color Doppler images -Doppler vortography. Doppler vortography relies on the centrosymmetric properties of the vortices. Such properties induce particular symmetries in the Doppler flow data that can be exploited to describe the vortices quantitatively. For this purpose, a kernel filter was developed to derive a parameter, the blood vortex signature (BVS), that allows detection of the main intracardiac vortices and estimation of their core vorticities. The reliability of Doppler vortography was assessed in mock Doppler fields issued from simulations and in vitro data. Doppler vortography was also tested in patients pared with vector flow mapping by echocardiography. Strong correlations were obtained between Doppler vortography-derived and ground-truth vorticities (in silico: r2 = 0.98, in vitro: r2 = 0.86, in vivo: r2 = 0.89). Our results indicate that Doppler vortography is a potentially promising echocardiographic tool for quantification of vortex flow in the left ventricle.
24210866
Correlation of virulence genes to clinical manifestations and outcome in patients with Streptococcus dysgalactiae subspecies equisimilis bacteremia.
Streptococcus dysgalactiae subsp. equisimilis (SDSE) is increasingly recognized as a human pathogen responsible for invasive infection and streptococcal toxic shock syndrome (STSS). The pathogen possesses virulence genes that resemble those found in Streptococcus pyogenes (GAS). We analyzed the association between these specific toxic genes, clinical presentations, and e in patients with SDSE infections.
24210867
Effectiveness of montelukast in pediatric patients with allergic rhinitis.
Allergic rhinitis (AR) is one of the mon chronic diseases of childhood and carries significant morbidity as well as physical and psychosocial consequences. Therapy aims to alleviate clinical symptoms, plications and improve psychosocial consequences. Leukotrienes which are amongst the main mediators in pathogenesis of AR have chemotactic properties and lead to increased vascular permeability. Thus, leukotriene antagonism may be an effective therapeutic option in treatment of allergic diseases, specifically AR. Montelukast which is a leukotriene receptor type I inhibitor has variable efficacy in children with AR and the guidelines mend its use in children with seasonal AR aged six years and above. Although its efficacy is inferior to anti-histamines and intranasal bination treatment may warrant clinical efficacy. Therefore, montelukast may be considered to be a well-tolerated therapeutic option for children with AR with minor side effects though long term results need to be assessed. In conclusion, larger scale research enrolling pediatric cases with seasonal and persistent AR are required before concise mendations about montelukast use in pediatric AR can be made.
24210868
A usability evaluation of medical software at an expert conference setting.
A usability test was employed to evaluate two medical software applications at an expert conference setting. One software application is a medical diagnostic tool (electrocardiogram [ECG] viewer) and the other is a medical research tool (electrode misplacement simulator [EMS]). These novel applications have yet to be adopted by the healthcare domain, thus, (1) we wanted to determine the potential user acceptance of these applications and (2) we wanted to determine the feasibility of evaluating medical diagnostic and medical research software at a conference setting as opposed to the conventional laboratory setting.
24210869
A haptic pedal for surgery assistance.
The research and development of mechatronic aids for surgery is a persistent challenge in the field of robotic surgery. This paper presents a new haptic pedal conceived to assist surgeons in the operating room by transmitting real-time surgical information through the foot. An effective human-robot interaction system for medical practice must exchange appropriate information with the operator as quickly and accurately as possible. Moreover, information must flow through the appropriate sensory modalities for a natural and simple interaction. However, users of current robotic systems might experience cognitive overload and be increasingly overwhelmed by data streams from multiple modalities. A new haptic channel is thus explored plement and improve existing systems. A preliminary set of experiments has been carried out to evaluate the performance of the proposed system in a virtual surgical drilling task. The results of the experiments show the effectiveness of the haptic pedal in providing surgical information through the foot.
24210870
Differential correlations between inflammatory cytokines and psychopathology in veterans with schizophrenia: potential role for IL-17 pathway.
Pro-inflammatory cytokines have been consistently reported to be elevated in schizophrenia patients. However, it is not known whether cytokines influence the presentation of psychotic symptoms. To address this issue, we evaluated the relationship between levels of inflammatory molecules and psychopathological parameters in patients with schizophrenia. We hypothesized that severity of symptoms would correlate with increased levels of inflammatory cytokines. Serum samples from 47 veterans with a diagnosis of schizophrenia and 20 healthy controls were tested for levels of 38 cytokines/chemokines involved in regulation of immune/inflammatory reactions using a Millipore multiplex bead array in a Luminex 100 system. We found significantly increased levels of GRO, MCP-1, MDC, and sCD40L, and significantly decreased levels of IFN-γ, IL-2, IL-12p70, and IL-17, in schizophrenia pared to controls. In addition, we observed positive correlations between levels of cytokines and the Positive and Negative Symptoms Scale (PANSS) scores in subjects with schizophrenia for G-CSF, IL-1β, IL1ra, IL-3, IL-6, IL-9, IL-10, sCD40L and TNF-β. Pathway analyses showed these cytokines to be part of the IL17 pathway. Using ponent analyses, we found the factor that included these cytokines and IL-17 to be associated with positive, general and total PANSS scores. These results suggest that alterations in this pathway may play a role in development of psychotic symptoms in schizophrenia.
24210871
Can P300 distinguish among schizophrenia, schizoaffective and bipolar I disorders? An ERP study of response inhibition.
Research utilizing visual event-related brain potentials (ERPs) has demonstrated that reduced P300 amplitude and prolonged latency may qualify as a biological marker (biomarker) for schizophrenia (SZ). We examined P300 characteristics in response inhibition among three putatively distinct psychopathology groups including schizophrenia (SZ), bipolar I disorder (BD) and schizoaffective disorder (SA) parison with healthy controls (CT) to determine their electrophysiological distinctiveness. In two separate studies, deficits in response inhibition indexed by the ponent were investigated using a lateralized Go/NoGo task. We hypothesized that deficits in response inhibition would be present and distinctive among the groups. In both studies, SZ showed response inhibition deficits as measured by P300 when stimuli were presented to the right visual field. In Study 2, delayed cognitive stimulus evaluation was observed in BD as indexed by prolonged P300 latency for NoGo trials. Six selected NoGo P300 variables out of thirty six NoGo P300 variables (18 amplitude, 18 latency) correctly classified SZ (79%), SA (64%) in Study 1 and seven variables selected in Study 2 classified CT (80%), and SZ (61%), BD (67%) and CT (68%) with the accuracy higher than chance level (33%). The findings suggest that distinct P300 features in response inhibition may be biomarkers with the capacity to distinguish BD and SZ, although SA was not clearly distinguishable from SZ and CT.
24210872
A review of ligand tethered surface engineered carbon nanotubes.
Carbon nanotubes (CNTs) have emerged as fascinating materials, exhibiting promising potential in receptor based targeting owing to their unique physicochemical properties (cell membrane penetration, high surface area and drug payload, patibility, easy surface modification, photoluminescence property, and non-immunogenicity etc). The hydrophilicity, a major constrain associated with the first generation of CNTs i.e. pristine CNTs, could be e using functionalization techniques. In the last two decades variety of functionalized CNTs (f-CNTs) i.e. oxidized, amidated, acylated, surfactant and biopolymer-assisted, and biomolecules modified have been developed and utilized as effective, safe, nano sized, and smart systems to deliver a wide range of bioactives in the biological system. The purpose of this review is to examine the various aspects of conjugation and associated conjugation chemistry of various targeting ligands to CNTs for their respective biomedical applications. The various biomolecules have been easily tethered to CNTs surfaces including proteins and amino acid, enzymes, nucleic acid (DNA and siRNA), aptamers, vitamins, monoclonal antibodies, peptides (NGR, RGD and Aniopep-2) and so on, for targeting purposes.
24210874
Control of angiogenesis by VEGF and endostatin-encapsulated protein microcrystals and inhibition of tumor angiogenesis.
Encapsulation of cytokines within protein microcrystals (polyhedra) is a promising approach for the stabilization and delivery of therapeutic proteins. Here, we investigate the influence of vascular endothelial growth factor (VEGF) microcrystals and endostatin microcrystals on angiogenesis. VEGF was successfully encapsulated into microcrystals derived from insect cypovirus with overexpression of protein disulfide bond isomerase. VEGF microcrystals were observed to increase the phosphorylation of p42/p44 MAP kinase and to stimulate the proliferation, migration, and network and tube formation of human umbilical vein endothelial cells (HUVECs). Endostatin was also successfully encapsulated into microcrystals. Endostatin microcrystals showed antiangiogenesis activities and inhibited the migration, and network and tube formation of HUVECs. Local administration of endostatin microcrystals in mice inhibited both angiogenesis and tumor growth with clear significant differences between treatment and control groups. Endostatin microcrystals only affected angiogenesis, but had no significant effect on pared to controls. Local therapy using endostatin microcrystals offers a potential approach to achieve sustained therapeutic release of antiangiogenic molecules for cancer treatment.
24210873
Mechanoregulation of valvular interstitial cell phenotype in the third dimension.
A quantitative understanding of plex interactions between cells, soluble factors, and the biological and mechanical properties of biomaterials is required to guide cell remodeling toward regeneration of healthy tissue rather than fibrocontractive tissue. In the present study, we characterized bined effects of boundary stiffness and transforming growth factor-β1 (TGF-β1) on cell-generated forces and collagen accumulation. We first generated a quantitative map of cell-generated tension in response to these factors by culturing valvular interstitial cells (VICs) within micro-scale fibrin gels pliant posts (0.15-1.05 nN/nm) in chemically-defined media with TGF-β1 (0-5 ng/mL). The VICs generated 100-3000 nN/cell after one week of culture, and multiple regression modeling demonstrated, for the first time, quantitative interaction (synergy) between these factors in a three-dimensional culture system. We then isolated passive and ponents of tension within the micro-tissues and found that cells cultured with high levels of stiffness and TGF-β1 expressed myofibroblast markers and generated substantial residual tension in the matrix yet, surprisingly, were not able to generate additional tension in response to membrane depolarization signifying a state of continual maximal contraction. In contrast, negligible residual tension was stored in the low stiffness and TGF-β1 groups indicating a lower potential for shrinkage upon release. We then studied if ECM could be generated under the low tension environment and found that TGF-β1, but not EGF, increased de novo collagen accumulation in both low and high tension environments roughly equally. Combined, these findings suggest that isometric cell force, passive retraction, and collagen production can be tuned by independently altering boundary stiffness and TGF-β1 concentration. The ability to stimulate matrix production without inducing high active tension will aid in the development of robust tissue engineered heart valves and other connective tissue replacements where minimizing tissue shrinkage upon implantation is critical.
24210875
Nanoparticle-directed sub-cellular localization of doxorubicin and the sensitization breast cancer cells by circumventing GST-mediated drug resistance.
Resistance to single or multiple chemotherapeutic drugs is a plication in clinical oncology and is one of the mon treatment limitations in patients with reoccurring cancers. Nanoparticle (NP)-based drug delivery systems (DDS's) have been shown to e drug resistance in cancer cells mainly by avoiding the activation of efflux pumps in these cells. We demonstrate in this work that polyester-based hyperbranched dendritic-linear (HBDL)-based NPs carrying doxorubicin (Dox) can effectively e microsomal glutathione transferase 1 (MGST1)-mediated drug resistance in breast cancer cells. Our DDS was much more effective at considerably lower intracellular Dox concentrations (IC50 6.3 μm vs. 36.3 μm) and achieved significantly greater reductions in viability and induced higher degrees of apoptosis (31% vs. pared to the free drug in the resistant cells. Dox-loaded HBDL NPs were found to translocate across the membranes of resistant cells via active endocytic pathways and to be transported to lysosomes, mitochondria, and the endoplasmic reticulum. A significantly lower amount of Dox accumulated in these partments in resistant cells treated with free Dox. Moreover, we found that Dox-HBDL significantly decreased the expression of MGST1 and enhanced mitochondria-mediated apoptotic cell pared to free Dox. Dox-HBDL also markedly activated the JNK pathway that contributes to the apoptosis of drug-resistant cells. These results suggest that HBDL NPs can modulate subcellular drug distribution by specific endocytic and trafficking pathways and that this results in drug delivery that alters enzyme levels and cellular signaling pathways and, most importantly, increases the induction of apoptosis. Our findings suggest that by exploiting the cell transport machinery we can optimize the polymeric vehicles for controlled drug release to e drug bat drug resistance with much higher efficacy.
24210876
Relationship between conventional semen characteristics, sperm motility patterns and fertility of Andalusian donkeys (Equus asinus).
Sperm quality has an important role in determining fertility. The aims of this study were pare the conventional sperm parameters, plus the characteristics of the motility patterns of the different sperm subpopulations, of donkey donors with different fertility level, and to determine their relationships to fertility. Thirty ejaculates from 6 Andalusian donkeys were assessed for gel-free volume, pH, sperm concentration, motility and morphology. The fertility of donkeys was classified on the basis of pregnancy rates per cycle, where donkeys with a per cycle pregnancy rate ≥60% were considered to be "fertile" (n=3) and those with a per cycle pregnancy rate <40% were categorized to be "sub-fertile" (n=3). Significant differences (P<0.001) between the "fertile" and the "sub-fertile" group were found for total and progressive motility, and for straight line velocity. Sperm variables associated (P<0.05) with an increase in percent pregnant per cycle included total motility (r=0.37), progressive motility (r=0.53), curvilinear velocity (r=0.44), straightness (r=0.39), beat cross frequency (r=0.44), and gel-free volume (r=0.53). Four sperm subpopulations (sP) were identified in fresh semen: sP1 (slow and non-progressive spermatozoa, 20%), sP2 (moderately slow but progressive spermatozoa, 71.2%), sP3 (highly active but non-progressive spermatozoa, 2.9%), and sP4 (highly active and progressive spermatozoa, 5.9%). The lowest percentage (3.1%; P<0.001) of sP4 spermatozoa was observed in the "sub-fertile" group. Three of the sperm subpopulations were related (P<0.05) to fertility (sP2, r=0.54; sP3, r=0.45; sP4, r=0.56). In conclusion, we were able to relate the fertility of donkeys with in vitro measures of sperm motility puter-assisted sperm analysis techniques.
24210877
The research of nanoparticles as gene vector for tumor gene therapy.
With the development of molecular biology, the application of the gene therapy es a tendency in the development of oncotherapy. The gene therapy has been acknowledged as the major progress of modern medicine, also a focus in the oncotherapy research. Commonly vectors of the gene therapy mainly include two categories, namely, viral vectors and nonviral vectors. Nanoparticles gene vector of various different kinds of materials, which belong to non-viral carriers. It presents excellent abilities of adsorption, concentration and protection of DNA, which can be attributed as a main reason of the adsorption and operation of nano-gene vector on exogenous genes. In this article, we mainly reviewed the recent studies of the characteristics of nanoparticles, characteristics and transport mechanism of nanoparticles as gene vector, the progress on nanoparticles as gene vector in tumor gene therapy. Nano-gene vectors, as new drug and gene carriers, present characteristics such as the controlled-release, targeting, and the improvement of bioavailability. Nanoparticles for cancer imaging and therapy have evolved rapidly during the last decade and it is expected that more and more will e clinical practise. In the near future, as a new nanometer gene delivery vector will be in medical research and treatment play a bigger role.
24210878
The positive effects of the revised milk and cheese allowances in the special supplemental nutrition program for women, infants, and children.
In 2009, the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) implemented revisions to the WIC food packages. Milk and cheese allowances were reduced, and whole milk was disallowed for participants older than 23 months. Using a pre-post research design and scanner data from a New England supermarket chain on purchases of WIC households, this article assesses how the new WIC packages affected milk and cheese purchases and saturated fat intake among WIC households in Connecticut and Massachusetts. Milk and cheese volume purchased by 515 WIC households in Connecticut pared before and after the WIC revisions (2009-2010) using generalized estimating equation models. Analysis for Massachusetts was descriptive. After implementation of the new WIC packages in Connecticut, whole-milk share declined from about 60% to 25% in WIC milk purchases, but remained flat at about 50% for purchases with non-WIC funds. Total milk volume fell by 14.2% (P<0.001), whole milk by half (P<0.001), and WIC-eligible cheese by 37.2% (P<0.001). Restrictions on whole milk shifted WIC purchases to reduced-fat milk in Connecticut and low-fat milk in Massachusetts, where reduced-fat milk is not permitted by WIC. The amounts of saturated fat from purchased milk and cheese declined by 85 g/month per WIC household in Connecticut and 107 g/month in Massachusetts. The 2009 WIC revisions led to a substantial decrease in purchases of whole milk and cheese among WIC families in New England. The related reduction in saturated fat intake could have important public health implications.
24210879
320-Row wide volume CT significantly reduces density heterogeneity observed in the descending aorta: comparisons with 64-row helical CT.
The aim of this study was pare density heterogeneity on wide volume (WV) scans with that on helical CT scans. 22 subjects underwent chest CT using 320-WV and 64-helical modes. Density heterogeneity of the descending aorta was evaluated quantitatively and qualitatively. At qualitative assessment, the heterogeneity was judged to be smaller on WV scans than on helical scans (p<0.0001). Mean changes in aortic density between two contiguous slices were 1.64 HU (3.40%) on WV scans and 2.29 HU (5.19%) on helical scans (p<0.0001). CT density of thoracic organs is more homogeneous and reliable on WV scans than on helical scans.
24210880
Physical fitness in pre-registration nursing students.
Nurses are ideally placed to deliver health promotion interventions, including physical fitness, however evidence suggests that nurses themselves are failing to engage in healthy lifestyles; this in turn making them less likely to promote health. It would appear that some nurses are allowing their own values, beliefs and behaviours to hinder this role. We propose these nurses are in breach of the Nursing and Midwifery (NMC) code. Currently nurses self declare their fitness to practice through the NMC, however self-monitoring has been criticized for its lack of reliability. Recruitment of student nurses in the UK does not currently assess physical fitness levels in line with other professionals such as the armed forces, police or fire service. Over half the nursing workforce is now overweight or obese, with alarming levels of inactivity. Physical activity positively correlates with motivation, wellbeing, coping and positive attitude. These attributes in turn impact on employability, retention and absence. This article explores promoting health, focussing on physical activity and discusses innovative ideas to promote physical activity within the nursing Curricula.
24210881
Experiencing everyday ethics in context: frontline data collectors perspectives and practices of bioethics.
Data collectors play a vital role in producing scientific knowledge. They are also an ponent in understanding the practice of bioethics. Yet, very little attention has been given to their everyday experiences or the context in which they are expected to undertake these tasks. This paper argues that while there has been extensive philosophical attention given to 'the what' and 'the why' in bioethics - what action is taken place and why - these should be considered along 'the who' - who are the individuals tasked with bioethics and what can their insights bring to macro-level and abstract discussions of bioethics. This paper will draw on the philosophical theories of Paul Ricoeur pliments a sociological examination of data collectors experiences and use of their agency coupled with a concern for contextual and institutional factors in which they worked. In emphasising everyday experiences and contexts, I will argue that data collectors' practice of bioethics was shaped by their position at the frontline of face-to-face interactions with medical research participants munity members, alongside their own personal ethical values and motivations. Institutional interpretations of bioethics also imposed certain parameters on their bioethical practice but these were generally peripheral to their sense of obligation and the expectations conferred in witnessing the needs and suffering of those they encountered during their quotidian research duties. This paper will demonstrate that although the principle of autonomy has dominated discussions of bioethics and gaining informed consent seen as a central facet of ethical research by many research institutions, for data collectors this principle was seldom the most important marker of their ethical practice. Instead, data collectors were concerned with remedying the dilemmas they encountered through enacting their own interpretations of justice and beneficence and imposing their own agency on the circumstances they experienced. Their practice of bioethics demonstrates their contribution to the conduct of research and the ings of an over-emphasis on autonomy.
24210882
Challenging resistance mechanisms to therapies for metastatic melanoma.
Melanoma is the most aggressive form of skin cancer and, if spread outside the epidermis, has a dismal prognosis. Before the approval of the anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibody ipilimumab and the BRAF inhibitors vemurafenib and dabrafenib, no other agents had demonstrated better results in terms of overall survival than the pound dacarbazine (or its oral analog temozolomide). However, most patients with metastatic melanoma do not obtain long-lasting clinical benefit from ipilimumab and responses to BRAF inhibitors are short lived. bination therapies with inhibitors of DNA repair (e.g., poly(ADP-ribose) polymerase [PARP] inhibitors), novel immunomodulators (monoclonal antibodies against programmed death-1 [PD-1] or its ligand PD-L1), targeted therapies (mitogen-activated protein kinase [MAPK]/extracellular signal-regulated kinase [ERK] kinase [MEK] or phosphatidylinositol 3-kinase [PI3K]/AKT/mammalian target of rapamycin [mTOR] inhibitors) or antiangiogenic agents are currently being investigated to improve the efficacy of antimelanoma therapies. This review discusses the implications of simultaneously targeting key regulators of melanoma cell proliferation/survival and immune responses to counteract resistance.
24210883
Dendritic cell immunoreceptor: a novel receptor for intravenous immunoglobulin mediates induction of regulatory T cells.
Intravenous immunoglobulin (IVIg) is a polyclonal IgG preparation with potent immunomodulating properties. Our laboratory demonstrated that IVIg significantly increases numbers of forkhead box protein 3-positive regulatory T (Treg) cells through generation of tolerogenic dendritic cells (DCs) in an allergic airways disease model.
24210884
Increased expression of bronchial epithelial transient receptor potential vanilloid 1 channels in patients with severe asthma.
The airway epithelium is exposed to a range of physical and chemical irritants in the environment that are known to trigger asthma. Transient receptor potential (TRP) cation channels play a central role in sensory responses to noxious physical and chemical stimuli. Recent genetic evidence suggests an involvement of transient receptor potential vanilloid 1 (TRPV1), one member of the vanilloid subfamily of TRP channels, in the pathophysiology of asthma. The functional expression of TRPV1 on airway epithelium has yet to be elucidated.
24210886
Brain natriuretic peptide at discharge as a predictor of 6-month mortality in acute decompensated heart failure.
Brain natriuretic peptide (BNP) is well established in detecting acute pensation of heart failure (ADHF). The role of BNP at discharge in predicting mortality is less established. Accumulating evidence suggests that inflammatory cytokines play an important role in the development of heart failure. We aimed to examine the contribution of BNP, interleukin 6, and procalcitonin to mortality in ADHF.
24210887
Association between mean arterial blood gas tension and outcome in cardiac arrest patients treated with therapeutic hypothermia.
Studies investigating the relationship between blood gas tension and e in cardiac arrest survivors have reported conflicting results. This might have resulted from the use of a blood gas value at a single time point and the difference in the proportion of patients treated with therapeutic hypothermia (TH). We investigated the association of the mean blood gas tensions calculated from blood gas values obtained between restoration of spontaneous circulation and end of TH with the e in cardiac arrest patients treated with TH.
24210888
Stress-related cardiomyopathy, ventricular dysfunction, artery thrombosis: a hidden pheochromocytoma.
Clinical presentation of pheochromocytoma can vary, and it can sometimes mimic other diseases. Some patients with pheochromocytoma may have atypical presentations, such as clinical features consistent with an acute coronary syndrome, that only later suggest a classical picture of stress-related cardiomyopathy. To our best knowledge, pheochromocytoma has been incidentally revealed in a few cases of catecholamine-induced cardiomyopathy and in only 1 case of peripheral arterial thrombosis. This is the first case of pheochromocytoma revealed after left ventricular dysfunction caused by stress-related cardiomyopathy associated with inferior limb artery thrombosis in a patient with plex cardiovascular history.
24210889
Quality of chest compressions during compression-only CPR: a comparative analysis following the 2005 and 2010 American Heart Association guidelines.
The latest guidelines both increased the requirements of pression rate and depth during cardiopulmonary resuscitation (CPR), which may make it more difficult for the rescuer to provide high-quality pression. In this study, we investigated the quality of pressions pression-only CPR under the latest 2010 American Heart Association (AHA) guidelines (AHA 2010) and its effect on rescuer fatigue.
24210890
Halogenated phenolic compound determination in plasma and serum by solid phase extraction, dansylation derivatization and liquid chromatography-positive electrospray ionization-tandem quadrupole mass spectrometry.
A robust, sensitive and accurate method was developed for the simultaneous determination in plasma and serum of suite a halogenated pounds (HPCs) for which several are known to persist in the environment and analytically pure standards are available. Namely, 14 congeners of hydroxylated polybrominated diphenyl ethers (OH-PBDEs), six congeners of hydroxylated polychlorinated biphenyls (OH-PCBs), pentachlorophenol, pentabromophenol and the flame retardant tetrabromobisphenol A (TBBPA). Solid phase extraction (SPE) enriched the pounds and cleaned up the samples as a result of efficient adsorption on a strong anion-exchange solid phase SPE cartridge (Oasis MAX). After final clean-up the HPCs were derivatized with dansyl chloride and analyzed by liquid chromatography-tandem mass spectrometry with electrospray ionization in positive mode (ESI(+)). Chromatographic separation was achieved on a Luna PFP(2) column (2mm×100mm, 3μm particle size) with mobile phases of water and acetonitrile (both containing 0.1% formic acid). The addition of the dansyl moiety to the HPCs greatly improved analyte sensitivity as the electrospray ionization efficiency was enhanced. Instrument limits of detection (ILODs) for LC-ESI(+)-MS/MS analysis of the HPCs were in the range of 0.01-0.07ng/mL and the method limits of quantification (MLOQs) were in the range of 0.02-0.15ng/g. Recovery efficiencies of the suite of HPCs ranged from 64% to 118% with relative standard deviations from 2% to 12% from fortified bovine serum samples. The method was successfully applied for HPC determination in representative polar bear and snapping turtle plasma samples.
24210891
High performance liquid chromatography with evaporative light scattering detection for the characterisation of a vesicular delivery system during stability studies.
A normal phase high performance liquid chromatography method with evaporative light scattering detection was developed for the simultaneous quantification of the lipid constituents of a non-ionic surfactant vesicle (NIV) delivery system consisting of tetra-ethylene glycol mono n-hexadecyl ether, cholesterol and dicetyl phosphate. An accelerated stability study performed at 25°C/60% relative humidity (RH) and 40°C/75% RH indicated that the NIV were chemically stable. Similar results were observed when stored at 4°C for 469 days. This chromatographic method developed is a sensitive, robust and high throughput analytical technique that offers the potential for rapid quantification of lipids in liposomal and vesicular systems. The results of the chromatographic studies were supported by parallel size and zeta potential measurements.

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