[Drug-facilitated crime and sexual abuse: a pediatric observation].
Drug-facilitated crime in sexual assault situations remains insufficiently recognized by physicians. In the possible context of an assault and in front of recent neuropsychicological disturbances in a child, such an issue has to be considered. The quality of sampling, the use of ultra-sensitive and specific toxicologic methods and a clinical-biological collaboration allow to recognize this form of delinquency whose consequences are both medical and legal.


Effects of strategy sequences and response-stimulus intervals on children's strategy selection and strategy execution: a study in computational estimation.
The present study investigates how children's better strategy selection and strategy execution on a given problem are influenced by which strategy was used on the immediately preceding problem and by the duration between their answer to the previous problem and current problem display. These goals are pursued in the context of an arithmetic problem solving task. Third and fifth graders were asked to select the better strategy to find estimates to two-digit addition problems like 36 + 78. On each problem, children could choose rounding-down (i.e., rounding both operands down to the closest smaller decades, like doing 40 + 60 to solve 42 + 67) or rounding-up strategies (i.e., rounding both operands up to the closest larger decades, like doing 50 + 70 to solve 42 + 67). Children were tested under a short RSI condition (i.e., the next problem was displayed 900 ms after participants' answer) or under a long RSI condition (i.e., the next problem was displayed 1,900 ms after participants' answer). Results showed that both strategy selection (e.g., children selected the better strategy more often under long RSI condition and after selecting the poorer strategy on the immediately preceding problem) and strategy execution (e.g., children executed strategy more efficiently under long RSI condition and were slower when switching strategy over two consecutive problems) were influenced by RSI and which strategy was used on the immediately preceding problem. Moreover, data showed age-related changes in effects of RSI and strategy sequence on mean percent better strategy selection and on strategy performance. The present findings have important theoretical and empirical implications for our understanding of general and specific processes involved in strategy selection, strategy execution, and strategic development.


[Ocular coloboma associated with cervico-oculo-acoustic syndrome].
Cervico-oculo-acoustic syndrome is an uncommon syndrome consisting of Klippel Feil syndrome, deafness, and Duane syndrome. We relate a new case of cervico-oculo-acoustic syndrome. We report the case of 15-month-old girl referred for esotropia of the right eye. Ocular examination revealed type 1 Stilling Duane syndrome in the right eye, in which we also noted microcornea, iris coloboma, and papillary and inferior chorioretinal coloboma sparing the macular area. The left eye was normal. The physical examination revealed Klippel Feil syndrome characterized by an extremely short neck with limited movement, a low posterior head line and fusion of the cervical vertebrae on radiography. The association of hearing loss (due to agenesis of the external ear) with Klippel Feil syndrome and Stilling Duane syndrome confirmed the diagnosis of cervico-oculo-acoustic syndrome. This case is unique because of the association of cervico-oculo-acoustic syndrome with ocular coloboma of the right eye. This association has not been reported previously in the literature.


Controlling Electron/Hole Recombination in Near-Infrared Polymer Phototransistors through an Insulation Medium: A Pathway to Ultrahigh Photosensitivity.
In near-infrared (NIR) polymer phototransistors, the photoresponse is proportional to the turn-on voltage shift (ΔVth). Due to the narrow band gap of NIR polymers, the ΔVth value is usually small. However, the use of a single bulk heterojunction (BHJ) layer has a minimal effect on increasing the value of ΔVth. This is because doping with high concentrations of acceptors results in strong current traps and accelerates electron/hole recombination. In this work, a new strategy is proposed to control the recombination of electrons/holes. By doping an insulating medium made of polystyrene (PS) into BHJs, PC61BM:PS:PDPP3T-based ternary NIR phototransistors with high acceptor concentrations were prepared by using a one-step film transfer method (FTM). Compared with a PC61BM:PDPP3T-based binary device (1:1), a ternary device (1:1:1) exhibited a significant performance improvement. The ΔVth value (∼29.5 ± 1.0 V) increased by approximately 4-fold, the Iph/Idark (∼4.4 × 106) increased by a factor of 3000 to 4000-fold, and the dark current decreased by 2-3 orders of magnitude (@ Vg = 0 V). Additionally, the ternary devices demonstrated excellent performance across a wide ternary ratio range (1:1:1 to 4:2:1).


Supramolecular therapeutics to treat the side effects induced by a depolarizing neuromuscular blocking agent.
Succinylcholine (Sch) is the only depolarizing neuromuscular blocking agent widely used for rapid sequence induction in emergency rooms. Unfortunately, a variety of (sometimes lethal) adverse effects, such as hyperkalemia and cardiac arrest, are associated with its use, and currently there are no specific antidotes to reverse Sch or to treat these side-effects. Methods: The binding behaviors of Sch and several synthetic receptors, including cucurbit[7]uril, sulfo-calix[4]arene and water-soluble carboxylatopillar[6]arene (WP[6]), were first investigated. With a mouse model, a leathal dose of Sch was selected for evaluation of the antidotal effects of these synthetic receptors on Sch induced mortality. The antidotal effects of a selected synthetic receptor, WP[6], on Sch induced cardiac arrhythmias, hyperkalemia, rhabdomyolysis and paralysis were subsequently evaluated with rat and mouse models. The reversal mechanism was also investigated at a cellular level. Results: All of these macrocyclic molecules exhibited relatively high binding affinities with Sch in vitro. In a Sch-overdosed mouse model, immediate injection of these synthetic receptors right after Sch administration increased the overall survival rate, with WP[6] standing out with the most effective antidotal effects. In addition, administration of WP[6] also reversed the paralysis induced by Sch in a mouse model. Moreover, infusion of WP[6] to Sch-overdosed rats reduced the incidence of cardiac arrhythmia, inhibited the otherwise abnormally high serum potassium levels, and relieved the muscular damage. At the cellular level, WP[6] reversed the Sch induced depolarization and reduced the efflux of intracellular potassium. Conclusion: Synthetic receptors, particularly WP[6], exhibited high binding affinities towards Sch, and presented a significant potential as supramolecular therapeutics to treat the various side effects of Sch by specifically sequestering Sch in vivo.


New LC-MS/MS Method for the Analysis of Allura Red Level in Takeaway Chinese Dishes and Urine of an Adult Chinese Population.
Allura red is a widely used synthetic food dye. In this study, we developed and validated a LC-MS/MS method for the quantification of allura red in three popular takeaway Chinese dishes (braised pork, soy sauce chicken, sweet and sour pork) and human urine samples. High levels of allura red ranging from 2.85 to 8.38 mg/g wet weight were detected in the surveyed Chinese dishes. Of 113 participants who frequently consume the surveyed Chinese dishes (>once a week in the past 2 years), the median of their urinary allura red level was 22.29 nM/mM creatinine (95% CI = 19.48-25.03) . Risk assessment using Cox proportional hazard models showed that a 10-fold increase in urinary allura red was positively associated with high blood pressure (odds ratio of 1.75 (95% CI = 0.78-3.96)). Our findings provide new insights for the potential risk of hypertension for long-term allura red overconsumption.


Acute asthma associated with sustained-release verapamil.
To describe a patient with asymptomatic bronchial asthma and hypertension who developed an acute asthma attack after receiving sustained-release verapamil. A 66-year-old white woman with a 10-year history of hypertension and bronchial asthma was switched from immediate-release verapamil hydrocloride 40 mg tid to sustained-release verapamil 240 mg/d po for better hypertension control. After taking the first tablet, she developed dyspnea, cough, and wheezing. Antiasthmatic medications were prescribed, but the asthma symptoms did not improve. She continued taking verapamil for 6 months, then, on her own, stopped all medications including the sustained-release verapamil, and her asthma symptoms disappeared. On rechallenge she developed severe dyspnea, cough, and wheezing 20 minutes after administration. The asthma resolved within 24 hours following three albuterol inhalations. The next day similar symptoms developed with rechallenge of the same brand of sustained-release verapamil in a 120-mg formulation, and verapamil was discontinued. Six months later she was again prescribed sustained-release verapamil 240 mg in another clinic where the physician was unaware of her previous reaction. Once again, severe dyspnea, cough, and wheezing developed. On four separate occasions the patient was challenged advertently or inadvertently, with sustained-release verapamil. Similar symptoms developed after each challenge and resolved after discontinuing this preparation. Although dyspnea associated with verapamil administration has been reported, this is the first report of an elderly asymptomatic asthmatic patient with hypertension who developed an acute asthma attack following sustained-release verapamil administration. Sustained-release verapamil is thought to be the cause of the asthma attack in this patient because she was not taking any other preparations; the symptoms started with the administration of sustained-release verapamil and were relieved after its discontinuation.


Hormone and receptor interplay in the regulation of mosquito lipid metabolism.
Mosquitoes transmit devastating human diseases because they need vertebrate blood for egg development. Metabolism in female mosquitoes is tightly coupled with blood meal-mediated reproduction, which requires an extremely high level of energy consumption. Functional analysis has shown that major genes encoding for enzymes involved in lipid metabolism (LM) in the mosquito fat bodies are down-regulated at the end of the juvenile hormone (JH)-controlled posteclosion (PE) phase but exhibit significant elevation in their transcript levels during the post-blood meal phase (PBM), which is regulated mainly by 20-hydroxyecdysone (20E). Reductions in the transcript levels of genes encoding triacylglycerol (TAG) catabolism and β-oxidation enzymes were observed to correlate with a dramatic accumulation of lipids in the PE phase; in contrast, these transcripts were elevated significantly and lipid stores were diminished during the PBM phase. The RNAi depletion of Methoprene-tolerant (Met) and ecdysone receptor (EcR), receptors for JH and 20E, respectively, reversed the LM gene expression and the levels of lipid stores and metabolites, demonstrating the critical roles of these hormones in LM regulation. Hepatocyte nuclear factor 4 (HNF4) RNAi-silenced mosquitoes exhibited down-regulation of the gene transcripts encoding TAG catabolism and β-oxidation enzymes and an inability to use lipids effectively, as manifested by TAG accumulation. The luciferase reporter assay showed direct regulation of LM-related genes by HNF4. Moreover, HNF4 gene expression was down-regulated by Met and activated by EcR and Target of rapamycin, providing a link between nutritional and hormonal regulation of LM in female mosquitoes.


Long-term intracerebral infusion of fibroblast growth factors restores motility and enhances F-DOPA uptake in parkinsonian monkeys.
Fibroblast growth factors (FGFs) are important for dopamine neurons in health and disease. Acidic (aFGF) and basic (bFGF) fibroblast growth factors increase the survival and growth of dopamine cells. Nigrostriatal dopamine neurons, the target cells for degeneration in Parkinson's disease, display receptors for basic fibroblast growth factor and these receptors are decreased in the brain of parkinsonian patients. We have investigated the effects of long-term intrastriatal infusion of FGFs in hemiparkinsonian monkeys. All animals were lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 0.4mgkg(-1), into the left internal carotid artery. The monkeys that had persistent asymmetric akinesia and contralateral rotation induced by apomorphine, were selected for chronic, unilateral, intracerebral infusion of neurotrophic factors or vehicle into the striatum ipsilateral to the lesion. Two animals received intrastriatal aFGF or bFGF, 2mugweek(-1), for 6 months. The controls received intrastriatal saline or intraventricular epidermal growth factor (EGF). F-DOPA positron emission tomography scans were performed in each animal before and after the intracerebral infusion of neurotrophic factors. We measured the tyrosine hydroxylase (TH) immunoreactive neurons in the substantia nigra and terminals in the striatum and evaluated the pathological complications related to the treatment or the delivery system. All four animals had, after the lesion with MPTP, a transient but incomplete recovery of akinesia. This period of spontaneous improvement was followed by a progressive deterioration of motor behaviour during the following months. The monkeys treated with FGFs, however, recovered quickly and persistently during the intracerebral infusion. F-DOPA uptake, prior to the intracerebral infusion, was greatly reduced in the lesioned striatum. The post-infusion F-DOPA scans revealed a 60% reduction respect to baseline in the lesioned striatum of the saline and EGF-infused animals. In the animals infused with FGFs, the post-infusion F-DOPA uptake increased more than 400% in the lesioned (and infused) striatum and around 200-300% in the contralateral side, with respect to the pre-infusion scan. The number of TH-positive cells in the substantia nigra correlated well with the uptake of F-DOPA in the post-infusion scan. No severe side-effects were present. Intrastriatal infusion of FGFs restores motor behaviour and increases F-DOPA striatal uptake in hemiparkinsonian monkeys.


Diet scores and cardio-metabolic risk factors among Guatemalan young adults.
We assessed the association of four diet quality scores with multiple cardio-metabolic outcomes among Guatemalan young adults experiencing the nutrition transition. We obtained cross-sectional dietary, demographic, anthropometric and cardio-metabolic risk factor data from 1220 Guatemalan adults (mean age 32.7 (sd 5.8) years) in 2002-4, and computed a Recommended Food Score (RFS), Not Recommended Food Score (NRFS), Food Variety Score (FVS) and the Dietary Quality Index-International (DQI-I). All four scores were correlated with energy intake (r 0.23-0.49; all P < 0.01), but had varying associations with socio-demographic characteristics, lifestyle factors and nutrient intakes. None of the scores was inversely associated with the metabolic syndrome or its components; rather some were positively associated with risk factors. Among both men and women the DQI-I was positively associated with BMI (kg/m2; beta = 0.10, 95 % CI 0.003, 0.21 (men); beta = 0.07, 95 % CI 0.01, 0.14 (women)) and waist circumference (cm; beta = 0.02, 95 % CI 0.01, 0.03 (men); beta = 0.02, 95 % CI = 0.01, 0.02 (women)). Among men, the RFS was positively associated with TAG (mg/l; beta = 0.11, 95 % CI 0.02, 0.21) and glucose (mg/l; beta = 0.13: 95 % CI 0.03, 0.22). We conclude that indices of diet quality are not consistently associated with chronic disease risk factor prevalence in this population of Guatemalan young adults.


Tannic Acid-Functionalized Silver Nanoparticles as Colorimetric Probe for the Simultaneous and Sensitive Detection of Aluminum(III) and Fluoride Ions.
In this study, we employed tannic acid (TA)-functionalized silver nanoparticles (TA@AgNPs) as colorimetric probe for the simultaneous and sensitive detection of Al(III) and F- ions. The proposed sensor was based on the aggregation and anti-aggregation effects of target Al(III) and F- ions on TA@AgNPs, respectively. Because of the strong coordination bond between Al(III) ions and TA, the addition of Al(III) ions to TA@AgNPs could cause aggregation and, hence, result in a significant change in the absorption and color of the test solution. Interestingly, in the presence of F- ions, the aggregation effect of Al(III) ions on TA@AgNPs can be effectively prevented. The extent of aggregation and anti-aggregation effects was concentration-dependent and can be used for the quantitative detection of Al(III) and F- ions. The as-proposed sensor presented the sensitive detection of Al(III) and F ions with limits of detection (LOD) of 0.2 and 0.19 μM, respectively. In addition, the proposed sensor showed excellent applicability for the detection of Al(III) and F- ions in real water samples. Moreover, the sensing strategy offered a simple, rapid, and sensitive detection procedure and could be used as a potential alternative to conventional methods, which usually involve sophisticated instruments, complicated processes, and a long detection time.


hATpin, a family of MITE-like hAT mobile elements conserved in diverse plant species that forms highly stable secondary structures.
We identified a 178 bp mobile DNA element in lettuce with characteristic CGAGC/GCTCG repeats in the subterminal regions. This element has terminal inverted repeats and 8-bp target site duplications typical of the hAT superfamily of class II mobile elements, but its small size and potential to form a single-stranded stable hairpin-like secondary structure suggest that it is related to MITE elements. In silico searches for related elements identified 252 plant sequences with 8-bp target site duplications and sequence similarity in their terminal and subterminal regions. Some of these sequences were predicted to encode transposases and may be autonomous elements; these constituted a separate clade within the phylogram of hAT transposases. We demonstrate that the CGAGC/GCTCG pentamer maximizes the hairpin stability compared to any other pentamer with the same C + G content, and the secondary structures of these elements are more stable than for most MITEs. We named these elements collectively as hATpin elements because of the hAT similarity and their hairpin structures. The nearly complete rice genome sequence and the highly advanced genome annotation allowed us to localize most rice elements and to deduce insertion preferences. hATpin elements are distributed on all chromosomes, but with significant bias for chromosomes 1 and 10 and in regions of moderate gene density. This family of class II mobile elements is found primarily in monocot species, but is also present in dicot species.


Dexamethasone treatment does not ameliorate subglottic ischemic injury in rabbits.
Following tracheal intubation, a small proportion of patients develop laryngeal inflammation or tissue necrosis severe enough to result in clinical symptoms. Although corticosteroids are frequently advocated to prevent such injury, human studies have been inconclusive because of the low incidence of the problem. This study developed a rabbit model of endotracheal tube-induced laryngeal injury to test the hypothesis that a corticosteroid, dexamethasone, could ameliorate the inflammation and necrosis. Subglottic injury was induced in 21 anesthetized rabbits by inflating the cuff of an endotracheal tube to 100 mm Hg with the cuff just below the vocal cords. Every 30 min for 2 h, the cuff was deflated, the tube turned 90 degrees, and the cuff then reinflated. After 2 h, the rabbits' tracheas were extubated. Rabbits were divided into two groups: the treatment group received dexamethasone (1 mg/kg) i.v. 1 h prior to extubation with the dose repeated 6 h following extubation; the untreated group received a saline solution placebo. Four additional rabbits were anesthetized for the same period but did not have a tracheal tube inserted. All rabbits were killed 24 h later and the larynxes were harvested. Sections through the larynx at the level of the cricoid cartilage were randomized and submitted blindly to a veterinary pathologist. Larynxes were scored and ranked according to the severity of mucosal inflammation and necrosis, and submucosal hemorrhage, edema, inflammation, and necrosis. Specimens were also evaluated for focal vs diffuse disease. Injured rabbits demonstrated focal to diffuse mucosal and submucosal inflammation and necrosis. Inflammatory exudates were present in sections from most of the injured rabbits and large sections of the larynxes were denuded of epithelium. There were no differences in injury scores between the treated and untreated rabbits. The four uninjured control rabbits had normal larynxes. Two hours of endotracheal tube cuff inflation to 100 mm Hg causes an inflammatory laryngeal injury. The histologic features of the injury are unaltered by treatment with 2 mg/kg dexamethasone.


Normal pressure hydrocephalus in geriatric medicine: a challenge.
Normal pressure hydrocephalus (NPH) in elderly patients is reviewed. Since the clinical signs that characterize NPH--incontinence, difficulty walking, and dementia--occur frequently in the elderly in association with a wide variety of disorders, attention is paid to the differential diagnosis of NPH on the basis of both clinical findings and laboratory tests. Success rates for treatment of NPH using surgical shunting are discussed, as are mortality rates and complication rates for this type of surgery in the elderly. Factors that may be of value in predicting which NPH patients are most likely to benefit from surgical intervention are reviewed, and the need for the development of pharmacological alternatives to surgery for elderly NPH patients is emphasized. As one of the most treatable causes of dementia in the elderly, NPH should be considered in the diagnosis of demented elderly patients with continence and gait disturbances, and it merits further research.


A triphasic orthotropic laminate model for cartilage curling behavior: fixed charge density versus mechanical properties inhomogeneity.
Osmotic pressure and associated residual stresses play important roles in cartilage development and biomechanical function. The curling behavior of articular cartilage was believed to be the combination of results from the osmotic pressure derived from fixed negative charges on proteoglycans and the structural and compositional and material property inhomogeneities within the tissue. In the present study, the in vitro swelling and curling behaviors of thin strips of cartilage were analyzed with a new structural model using the triphasic mixture theory with a collagen-proteoglycan solid matrix composed of a three-layered laminate with each layer possessing a distinct set of orthotropic properties. A conewise linear elastic matrix was also incorporated to account for the well-known tension-compression nonlinearity of the tissue. This model can account, for the first time, for the swelling-induced curvatures found in published experimental results on excised cartilage samples. The results suggest that for a charged-hydrated soft tissue, such as articular cartilage, the balance of proteoglycan swelling and the collagen restraining within the solid matrix is the origin of the in situ residual stress, and that the layered collagen ultrastructure, e.g., relatively dense and with high stiffness at the articular surface, play the dominate role in determining curling behaviors of such tissues.


cPKCγ-mediated down-regulation of UCHL1 alleviates ischaemic neuronal injuries by decreasing autophagy via ERK-mTOR pathway.
Stroke is one of the leading causes of death in the world, but its underlying mechanisms remain unclear. Both conventional protein kinase C (cPKC)γ and ubiquitin C-terminal hydrolase L1 (UCHL1) are neuron-specific proteins. In the models of 1-hr middle cerebral artery occlusion (MCAO)/24-hr reperfusion in mice and 1-hr oxygen-glucose deprivation (OGD)/24-hr reoxygenation in cortical neurons, we found that cPKCγ gene knockout remarkably aggravated ischaemic injuries and simultaneously increased the levels of cleaved (Cl)-caspase-3 and LC3-I proteolysis product LC3-II, and the ratio of TUNEL-positive cells to total neurons. Moreover, cPKCγ gene knockout could increase UCHL1 protein expression via elevating its mRNA level regulated by the nuclear factor κB inhibitor alpha (IκB-α)/nuclear factor κB (NF-κB) pathway in cortical neurons. Both inhibitor and shRNA of UCHL1 significantly reduced the ratio of LC3-II/total LC3, which contributed to neuronal survival after ischaemic stroke, but did not alter the level of Cl-caspase-3. In addition, UCHL1 shRNA reversed the effect of cPKCγ on the phosphorylation levels of mTOR and ERK rather than that of AMPK and GSK-3β. In conclusion, our results suggest that cPKCγ activation alleviates ischaemic injuries of mice and cortical neurons through inhibiting UCHL1 expression, which may negatively regulate autophagy through ERK-mTOR pathway.


Cardiac diphtheria in a previously immunized individual.
A previously healthy 19-year-old Asian female without significant past medical history presented to the emergency room complaining of a sore throat, difficulty in swallowing, fever, swollen neck, malaise, and myalgia for three to four days. The patient was initially seen at an outside hospital, evaluated by an ear, nose, and throat physician (ENT), and was found to have desquamative pharyngitis. The patient was transferred to our hospital after she continued to experience progressively worsening shortness of breath and went into acute respiratory distress. The patient was found to have laryngeal edema on exam with greenish-black, necrotic-looking tissue extending to the hypopharynx, nasopharynx, and oropharynx. A culture was taken. ENT was consulted for tracheostomy placement. The patient refused to have tracheostomy placed. She went into severe respiratory distress and required urgent tracheostomy. A cardiac consult was obtained. A 2D echocardiogram performed one day after admission revealed an ejection fraction (EF) of 10-20%, normal left ventricular cavity size, normal wall thickness, and severe global systolic dysfunction. There was mild to moderate mitral regurgitation and trace tricuspid regurgitation. The inferior vena cava was dilated and a 1 cm x 1.5 cm questionable mass or thrombus was seen. The patient's throat culture was positive for diphtheria. The CDC was contacted, and the patient was treated with antitoxin with prompt resolution of cardiac symptoms. A repeat echo done five days post-treatment showed improved EF of 65%, normal left ventricular thickness and function, with no clot visualized. She was treated with ceftriaxone and flagyl for ocular motor neuritis, otitis media, and strep. pneumonia with gradual improvement. These were all secondary to the diphtheria toxins, however, the patient continues to be followed as an outpatient by ENT for ongoing problems with swallowing, speech, and trach management.


Multifaceted death receptor 3 signaling-promoting survival and triggering death.
Death Receptor 3 (DR3) and its cognate ligand TL1A belong to the tumor necrosis factor superfamily (TNFSF). This sophisticated network of receptor-ligand systems controls innumerable biological processes. For many (if not all) TNFSF ligands and receptors, a role in conditions such as inflammation, tissue development, proliferation, and cell death has been firmly established. However, relatively little is known about DR3 and TL1A. Here, we review novel aspects of DR3 signaling and DR3-associated signaling pathways before summarizing the function of DR3 in the immune system. The emerging role of DR3 in disease will be addressed before we finally critically discuss the potential therapeutic exploitation of this receptor-ligand pair.


Performance profile of NCAA Division I men's basketball games and training sessions.
This study aimed to analyse live and stoppage time phases, their ratio, and action played on half and full court in college basketball games. Differences were assessed for the entire games and between halves. Moreover, differences of the live/stoppage time ratio were analysed between games and game-based conditioning drills. Ten games as well as fifteen defensive, fourteen offensive and six scrimmage-type drills of the same division I men's college team (13 players) were analysed using time-motion analysis technique. Live and stoppage time were classified in five classes of duration: 1-20, 21-40, 41-60, 61-80, >80 seconds. Half court actions started and finished in the same half court. Full court actions were classified as transfer (TR) phases when at least 3 teammates crossed the mid-court line. TR phases were then classified in 5 classes of frequency: 1TR, 2TR, 3TR, 4TR, and >4TR. The results revealed no statistically significant differences between games or between halves for the considered parameters. The only significant difference was observed for live/stoppage time ratio between halves (p<0.001). Furthermore, a significant difference of the live/stoppage ratio was found between games and game-based drills (p<0.01). Post-hoc analysis demonstrated significant differences of scrimmage-type drills in comparison to games, and defensive and offensive drills (p<0.05), whereas no differences emerged for the other pairwise comparisons. The absence of differences between games in the analysed parameters might be important to characterize the model of performance in division I men's college games. Furthermore, these results encourage coaches to use game-based conditioning drills to replicate the LT/ST ratio documented during games.


Factors associated with complications in gynecological surgeries.
To evaluate the factors associated with complications in major gynecological surgeries. A retrospective study on major gynecological surgeries performed at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia, from the year 1997-2001. A total of 555 cases were included. Risk factors associated with complications were evaluated by a unique regression analysis. High blood loss was associated with salpingectomy/salpingotomy, myomectomy, and total abdominal hysterectomy (TAH). Old age was associated with TAH, oophorectomy and vaginal hysterectomy. Prolonged hospitalization was associated with TAH and oophorectomy. Urinary tract infection, wound infection, nausea and vomiting were not significant postoperative complications in major gynecological surgeries. The recognition of the specific complications associated with each type of surgery are important for counseling the patients and preoperative preparation to reduce the risk of long term morbidity.


Dendrobium officinale Orchid Extract Prevents Ovariectomy-Induced Osteoporosis in Vivo and Inhibits RANKL-Induced Osteoclast Differentiation in Vitro.
Background:Dendrobium officinale, a traditional Chinese medical herb with high value that is widely used in Asia, possesses many positive effects on human health, including anti-chronic inflammation, anti-obesity, and immune modulation properties; however, whether D. officinale has inhibitory effects on postmenopausal osteoporosis remains unknown. Objective: We investigated the effects of D. officinale extract (DOE) on ovariectomy-induced bone loss in vivo and on osteoclastogenesis in vitro. Methods:In vivo, female rats were divided into a sham-operated (sham) group and five ovariectomized (OVX) subgroups: OVX with vehicle (OVX), OVX with Xian-Ling-Gu-Bao capsule (240 mg/kg body weight/day), and OVX with low-, medium-, and high-dose DOE (150, 300, and 600 mg/kg body weight/day, respectively). Animals in each group were administered their corresponding treatments for 13 weeks. Body weight, serum biochemical parameters, uterine and femoral physical parameters, bone mineral density (BMD), bone biomechanical properties, and bone microarchitecture were obtained. In vitro, the effects of DOE on osteoclastogenesis were examined using RAW264.7 cells. The effects of DOE on osteoclastogenesis and the expression of osteoclast-specific marker genes and proteins were determined. Results: DOE effectively ameliorated serum biochemical parameters, especially alleviated estradiol (E2) deficiency and maintained calcium and phosphorus homeostasis. DOE improved uterine and femoral physical parameters. In addition, DOE improved femoral BMD and biomechanical properties. DOE significantly ameliorated bone microarchitecture. Moreover, DOE inhibited osteoclastogenesis independent of its cytoxicity and suppressed the expression of osteoclast-specific marker genes and proteins. Conclusion: DOE can effectively prevent ovariectomy-induced bone loss in vivo and inhibit osteoclastogenesis in vitro.


Interferon-gamma induces receptor dimerization in solution and on cells.
The extracellular domain (ECD) of the human interferon-gamma (IFN gamma) receptor was stably expressed in Chinese hamster ovary cells and purified to homogeneity. Scatchard analysis of 125I-IFN gamma binding to ECD preparations revealed the formation of a ligand-receptor complex which displayed a Ka of 6.4 +/- 0.9 x 10(8) M-1. Two types of complexes were identified by sucrose density gradient ultracentrifugation. The stoichiometry of the major ECD-ligand complex was determined by high performance liquid chromatography gel filtration. When IFN gamma was incubated with a 2-fold molar excess of ECD, a 190-kDa complex was isolated that contained 2 mol of ECD per 1 mol of IFN gamma. IFN gamma also induced dimerization of IFN gamma receptors expressed at the cell surface as detected by chemically cross-linking receptor bound ligand and analyzing cell lysates by SDS-polyacrylamide gel electrophoresis and immunoblotting. Finally, labeled forms of ECD bound to cells preincubated at 4 degrees C with excess amounts of IFN gamma indicating that the ligand could associate with more than one receptor molecule in the absence of chemical cross-linking agents. These results demonstrate that IFN gamma effects dimerization of its receptor under physiologic conditions and suggest that IFN gamma receptor dimerization may be an important event in inducing IFN gamma-dependent biologic responses.


Pharmacological intervention in hypertension using beta-blockers: Real-world evidence for long-term effectiveness.
The study objective was to compare the long-term incidence and risk of mortality and cardiovascular outcomes in patients with hypertension initiating bisoprolol, other β-blockers or other antihypertensive therapies. Cohort analysis using UK Clinical Practice Research Datalink (CPRD). Adult patients with first diagnosis of hypertension recorded between 2000 and 2014, with ≥365 days of registration to first event and initiating monotherapies of bisoprolol, other β-blockers or drugs other than β-blockers within 6 months of diagnosis were included. Incidence rates (IR) for each treatment cohort were compared using adjusted hazard ratio (HR) and 95% confidence intervals (CI) obtained from Cox regression analyses. Of 100,066 patients included, 539 were prescribed bisoprolol, 3701 other β-blockers, and 95,826 drugs other than β-blockers. Patients receiving bisoprolol had significantly increased survival from 2 up to <15 years (HR for <15 years 0.34; 95% CI 0.18-0.67) versus other β-blockers, and from 5 to <15 years (HR for <15 years 0.52; 95% CI 0.27-1.00) versus drugs other than β-blockers. Over time, the risk of arrhythmia was higher in the bisoprolol cohort versus other β-blockers, and risks of arrhythmia and angina were higher versus drugs other than β-blockers. No differences in the risk of embolism, stroke, and myocardial infarction (MI) were found between cohorts. Over time, mortality and cardiovascular outcome IRs decreased in each cohort. In conclusion, bisoprolol showed sustained benefit on survival, evident from 2 years after treatment initiation versus other β-blockers, and from 5 years versus drugs other than β-blockers, providing long-term evidence supporting the use of bisoprolol in patients with hypertension in primary care.


'Don't let NHS pressures create another Mid Staffs'.
Current pressures in the health service are creating similar circumstances to those that led to disastrous failings at Mid Staffordshire NHS Foundation Trust, according to the nurse who was brought in to turn the organisation around.


Effect of essential oil compound on shedding and colonization of Salmonella enterica serovar Heidelberg in broilers.
The objectives of this study were to determine the effect of an essential oil blend (EO; carvacrol, thymol, eucalyptol, lemon) administered in drinking water on the performance, mortality, water consumption, pH of crop and ceca, and Salmonella enterica serovar Heidelberg fecal shedding and colonization in broiler birds following Salmonella Heidelberg challenge and feed withdrawal. Chicks were randomly assigned to water treatments containing 0.05, 0.025, or 0.0125% EO or untreated controls. Treatments were administered in drinking water on 0 to 7 and 35 to 42 d. One-half of the chicks were challenged with Salmonella Heidelberg and placed in pens with unchallenged chicks on d 1. Performance, mortality, water consumption, and pH were determined during the 42-d study. Prevalence of Salmonella Heidelberg was determined on drag swabs (0, 14, and 42 d) and in the ceca and crops (42 d). The 0.05% EO administered in drinking water significantly (P < 0.05) reduced Salmonella Heidelberg colonization in crops of challenged birds, significantly lowered the feed conversion ratio, and increased weight gain compared with controls. The 0.025% and 0.015% EO in drinking water significantly lowered the feed conversion ratio and increased weight gain compared with controls, but did not significantly reduce Salmonella Heidelberg colonization in the crops. The EO in drinking water did not significantly reduce Salmonella Heidelberg colonization in ceca or fecal shedding in broilers. The EO used in the study may control Salmonella Heidelberg contamination in crops of broilers when administered in drinking water and therefore may reduce the potential for cross-contamination of the carcass when the birds are processed.


Cauda equina syndrome: is the current management of patients presenting to district general hospitals fit for purpose? A personal view based on a review of the literature and a medicolegal experience.
There is no universally agreed definition of cauda equina syndrome (CES). Clinical signs of CES including direct rectal examination (DRE) do not reliably correlate with cauda equina (CE) compression on MRI. Clinical assessment only becomes reliable if there are symptoms/signs of late, often irreversible, CES. The only reliable way of including or excluding CES is to perform MRI on all patients with suspected CES. If the diagnosis is being considered, MRI should ideally be performed locally in the District General Hospitals within one hour of the question being raised irrespective of the hour or the day. Patients with symptoms and signs of CES and MRI confirmed CE compression should be referred to the local spinal service for emergency surgery. CES can be subdivided by the degree of neurological deficit (bilateral radiculopathy, incomplete CES or CES with retention of urine) and also by time to surgical treatment (12, 24, 48 or 72 hour). There is increasing understanding that damage to the cauda equina nerve roots occurs in a continuous and progressive fashion which implies that there are no safe time or deficit thresholds. Neurological deterioration can occur rapidly and is often associated with longterm poor outcomes. It is not possible to predict which patients with a large central disc prolapse compressing the CE nerve roots are going to deteriorate neurologically nor how rapidly. Consensus guidelines from the Society of British Neurological Surgeons and British Association of Spinal Surgeons recommend decompressive surgery as soon as practically possible which for many patients will be urgent/emergency surgery at any hour of the day or night.


The effect of profession on burnout in hospital staff.
A high level of burnout has been described in health professionals. However, literature regarding other hospital employees is scarce. To assess the prevalence of burnout in different professional groups of hospital staff and how the professional category is associated with levels of burnout. Employees of a University Hospital in Portugal completed a self-administered online questionnaire in 2014-2015. We used the Portuguese version of the Maslach Burnout Inventory-Human Services Survey and scored three dimensions of burnout (emotional exhaustion, depersonalization, personal accomplishment) as low, average or high. We estimated odds ratios (OR) and 95% confidence intervals (95% CI) by logistic regression, adjusting for age, sex, use of anxiolytic/antidepressant drugs and job satisfaction. There was a 10% response rate; 368 questionnaires were available for analysis. High levels of burnout due to emotional exhaustion were observed in all professional categories. Nurses, administrative staff and technicians more frequently scored higher levels of emotional exhaustion (59%, 50% and 50%, respectively) and lack of personal accomplishment (41%, 52% and 38%, respectively) than physicians and healthcare assistants. Not all professionals scored highly for depersonalization. Emotional exhaustion scores were significantly lower in healthcare assistants than nurses (adjusted OR 0.26, 95% CI 0.10-0.64). Burnout affects all professional categories of hospital staff. Future studies should use larger, more representative samples of hospital staff, perform longitudinal analyses and analyse data on specifics of each professional category and other potential confounders.


[Evaluation of a new anti-cancer drug regimen for surface epithelial-stromal ovarian cancer].
The purpose of this study was to describe a new anti-cancer drug regimen for epithelial ovarian cancer. The cytotoxicities of some anti-cancer drugs regimens against human epithelial ovarian cancer xenografted into nude mice (TOM, TOH, TON) have been studied. The activities of CDDP, CPT-11, TXL, CDDP + CPM, CDDP + CPT-11, CDDP + TXL, CPT-11 + CPM, CPT-11 + TXL, and TXL + CPM were evaluated comparing with a control group using saline. Three mice were used for each group, and when the xenografted tumor reached 6 mm in diameter, 1/5 LD50 of these drugs was administered into the peritoneal cavity of mice once a week for three weeks. The three most effective regimens were CPT-11 + TXL, CDDP + CPM, and CDDP + CPT-11 for epithelial ovarian cancer.


Anti-lymphocytic antibodies in autoimmune chronic active hepatitis starting in childhood.
Anti-lymphocytic antibodies (ALA) have been described in a variety of autoimmune disorders. We have investigated the presence of ALA in autoimmune chronic active hepatitis (aCAH) starting in childhood. Using a modified Terasaki technique ALA were found in 17 of 18 patients with aCAH but in only one of 15 patients with alpha-1-anti-trypsin deficiency or Wilson's disease and three of 27 age-matched healthy controls (P less than 0.0005 for both). Sera from 12 patients with uncontrolled aCAH had significantly higher cytotoxicity values than sera from six children with inactive diseases (P less than 0.01). ALA were directed to T but not B lymphocytes and were not reactive with specific HLA antigens. No preferential killing was observed against CD4 or CD8 positive T lymphocytes. Characterization of ALA revealed them to be cold-reactive IgM. The possible role of ALA in aCAH is discussed.


[Is gene technology immoral?].
Since it came into being in the USA in the early 1970s, gene technology has always been fundamentally controversial, especially in the German-speaking countries. The optimistic--or critical--supporters of gene technology are convinced that, in view of gene technology's not otherwise attainable advantages for human and animal health, for food production and other important aims, it would be ethically unacceptable to restrict to the minimum or even ban it. On the other hand, the radical critics are convinced that gene technology, in view of its anthropologically false starting-point, the questionable interests behind it, and above all its unforeseeable, serious negative implications for mankind and environment, is unacceptable on ethical grounds. Critical reflexion on these polarized arguments must start from the question why precisely gene technology is so controversial, and what are the criteria for ethical assessment. These reflexions presuppose that the prior judgement of gene technology as a technology in the ideological field is rooted in life attitudes, history and nature in general, and this is true not only of gene technology's opponents but also its supporters. It is thus a question of one ideology vs. another. Chief importance here attaches to the mankind-nature relationship and the need to take seriously the fundamental ambivalence of all (!) human action with unforeseeable consequences. The conclusion is that neither to demonize nor to glorify gene technology, as a matter of principle, does justice to its wide and varied positive or negative potential. The ethical assessment of gene technology must be differentiated according to the aims and possible implications.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of novel monoclonal antibodies on LIF-induced signaling in chicken blastodermal cells.
Leukemia-inhibitory factor (LIF) is indispensable for maintaining the undifferentiated state when propagating mouse embryonic stem (ES) cells. We previously cloned chicken LIF (chLIF) cDNA and demonstrated that it maintained chicken ES cell cultures in an undifferentiated state. Here, we developed two monoclonal antibodies, HUL-1 and HUL-2, against chLIF, which specifically recognized recombinant chLIF (rchLIF) produced by Escherichia coli and Chinese hamster ovary K1 cells, in enzyme-linked immunosorbent assays and Western blot analysis. In addition, HUL-2 inhibited the phosphorylation of signal transducer and activator of transcription 3 by rchLIF in chicken blastodermal cells (CBCs), but not that of mitogen-activated protein kinase kinase. Furthermore, the addition of HUL-2 to CBC cultures resulted in embryoid bodies forming earlier than in normal cultures. These results indicated that HUL-2 recognized not only rchLIF but also native chLIF, and suggested that CBCs in culture produce LIF, which functions in autocrine signaling.


The axotomy-induced neuropeptides galanin and pituitary adenylate cyclase-activating peptide promote axonal sprouting of primary afferent and cranial motor neurones.
The neuropeptides galanin and pituitary adenylate cyclase-activating peptide (PACAP) are markedly up-regulated in response to peripheral nerve lesion. Both peptides are involved in neuronal differentiation and neurite outgrowth during development. In this study, we investigated the effects of galanin and PACAP on axonal elongation and sprouting by adult rat sensory neurones in vitro and facial motor neurones in vivo. Dissociated rat dorsal root ganglion neurones were plated on laminin substrate and analysed morphometrically. Both the mean axonal length and the number of branch points significantly increased in the presence of galanin or PACAP (2-5 microm). Effects on axonal collateralization were investigated in the rat facial nerve lesion model by direct application of the peptides to collagen-filled conduits entubulating the transected facial nerve stumps. Triple retrograde labelling of brainstem neurones confirmed that the peptides potently induce axonal sprouting of cranial motor neurones. The number of neurones regenerating into identified rami of the facial nerve increased up to fivefold. Biometrical analysis of whisking behaviour revealed that galanin and PACAP impaired the functional outcome when compared with vehicle-treated animals 8 weeks after surgery. In conclusion, although galanin and PACAP have been established as neurotrophic molecules with respect to axonal development and regeneration, their potential as treatments for peripheral nerve lesions appears limited because of the extensive stimulation of collateral axon branching. These branches are misrouted towards incorrect muscles and cause impairment in their coordinated activity.


[Clinical pharmacokinetics of nitrosoureas].
The pharmacokinetic characteristics of chloroethylnitrosourea anti-cancer agents are based on their high chemical reactivity and subsequent rapid breakdown in the plasma; and on a widespread tissue distribution due to the molecules' lipophilic properties. These physico-chemical properties explain the main problems that one may face during pharmacokinetic studies (assay method, isolation of high reactive intermediates) and that are related to the typical pharmacokinetic profile of these agents: rapid gastro-intestinal absorption, short half-life, widespread pulmonary and renal distribution, passage through the blood-brain barrier with levels within a therapeutic range, lipoprotein fixation, mainly hepatic and pulmonary metabolism, renal excretion. A drug interaction with phenobarbital has been described in the rat. The rational use of these compounds in cancer chemotherapy requires the optimisation of assay methods and a better understanding of their transformation pathways as well as their mechanism of action.


Demonstration of glass transition temperature shift in thin supported polystyrene films by internal reference method.
An internal reference method is used for the first time to clearly demonstrate the glass transition temperature (Tg) depression effect in 5 nm thick polystyrene films spin-cast on silicon wafers. Initially flat films exhibit depressed Tg at approximately 85 °C. Temperature-induced dewetting on hexamethyldisilazane-treated silicon substrates leads to formation of discontinuous films with average effective thickness of 15-30 nm. Dewetted films demonstrate Tg close to the bulk value (≈ 100 °C) and are used as internal references. Data both for continuous and discontinuous films are obtained in the same experimental run for the same sample, which allows direct comparison between datasets. Phase-modulated ellipsometry in vacuum is used to monitor glass transition. Both traditional linear temperature scan method and a novel temperature modulated technique have been employed in the measurements.


J/ψ polarization at the Tevatron and the LHC: nonrelativistic-QCD factorization at the crossroads.
We study the polarization observables of J/ψ hadroproduction at next-to-leading order within the factorization formalism of nonrelativistic quantum chromodynamics. We complete the present knowledge of the relativistic corrections by also providing the contribution due to the intermediate (3)P(J)([8]) color-octet states at this order, which turns out to be quite significant. Exploiting the color-octet long-distance matrix elements previously extracted through a global fit to experimental data of unpolarized J/ψ production, we provide theoretical predictions in the helicity and Collins-Soper frames and compare them with data taken by CDF at Fermilab Tevatron I and II and by ALICE at CERN LHC. The notorious CDF J/ψ polarization anomaly familiar from leading-order analyses persists at the quantum level, while the situation looks promising for the LHC, which is bound to bring final clarification.


Correlation between the number of placental opioid receptors, mode of delivery, and maternal narcotic use.
Human placental opioid receptors were assayed using the radioactive opioid agonist, etorphine, to determine the number of binding sites in villous tissue membrane preparations. Significant differences in receptor concentration per milligram of protein of tissue were found between placentas obtained following vaginal or abdominal delivery (P less than 0.002). Labor itself did not alter apparent receptor numbers. In patients with maternal narcotic abuse during pregnancy, no opioid binding could be detected regardless of the mode of delivery, suggesting possible receptor down-regulation.


[Unintentional total spinal anesthesia during cervical epidural block with ropivacaine].
We present a case of unintentional total spinal anesthesia, which occurred during cervical epidural block. A 34-year-old man with complex regional pain syndrome of the right upper arm was treated with epidural block at C7-T1 interspace. Immediately after test-dose injection of ropivacaine 1.5 ml, he complained of paresthesia of his upper extremities. He developed difficulty talking and breathing. Subsequently he showed a complete paralysis with the loss of consciousness, respiratory arrest, and bilateral midriasis. Mandatory ventilation was started and endotracheal tube was placed. Eighty minutes after the injection of ropivacaine, he recovered consciousness and spontaneous respiration resumed. Checking adequate ventilation, his trachea was extubated. Neurological dysfunction was not seen thereafter. Although test-dose injection is recommended especially in high-risk patients and case of difficulty of epidural space identification, it does not fully prevent complications. For cervical epidural block, local anesthetics should either be given at small doses or not be given as long as a possibility of spinal injection is remaining.


Hydrogen peroxide as a topical hemostatic agent.
Many research efforts have been directed toward enhancing the bone-cement interface of total joint arthroplasties. Hemostatic agents have been popularized as effective means of retarding the development of potentially harmful debris interposition adjacent to, and blood lamination patterns within, the methylmethacrylate. The hemostatic effectiveness of hydrogen peroxide was tested on six metaphyseal bone beds in ten mongrel dogs: three sites were treated with hydrogen peroxide and three were saline-treated control sites. The hemostatic effect of the treatments was determined by comparing blood loss per unit area per minute before and after application of the test solutions. The results indicate that hydrogen peroxide is an effective hemostatic agent and reduces the amount of blood and debris trapped within the trabecular bone methylmethacrylate interface.


Emerging targets for treating sulfur mustard-induced injuries.
Sulfur mustard (SM; bis-(2-chlororethyl) sulfide) is a highly reactive, potent warfare agent that has recently reemerged as a major threat to military and civilians. Exposure to SM is often fatal, primarily due to pulmonary injuries and complications caused by its inhalation. Profound inflammation, hypercoagulation, and oxidative stress are the hallmarks that define SM-induced pulmonary toxicities. Despite advances, effective therapies are still limited. This current review focuses on inflammatory and coagulation pathways that influence the airway pathophysiology of SM poisoning and highlights the complexity of developing an effective therapeutic target.


Genomic alterations in blast phase of BCR::ABL1-negative myeloproliferative neoplasms.
The blast phase of BCR::ABL1-negative myeloproliferative neoplasm (MPN-BP) represents the final stage of the disease, which is complicated by complex genomic alterations. These alterations result from sequence changes in genetic material (DNA, RNA) and can lead to either a gain or loss of function of encoded proteins, such as adaptor proteins, enzymes, components of spliceosomes, cell cycle checkpoints regulators, transcription factors, or proteins in cell signaling pathways. Interference at various levels, including transcription, translation, and post-translational modification (such as methylation, dephosphorylation, or acetylation), can contribute to these alterations. Mutated genes such as ASXL1, EZH2, IDH1, IDH2, TET2, SRSF2, U2AF1, TP53, NRAS, KRAS, PTPN11, SH2B3/LNK, and RUNX1 play active roles at different stages of genetic material expression, modification, and protein function manipulation in MPNs. These mutations are also correlated with, and can contribute to, the progression of MPN-BP. In this review, we summarize their common mutational profiles, functions, and associations with progression of MPN-BP.


[Effect of Leflunomideon Inflammatory Factors and Immune Function in Rats with Chronic Glomerulonephritis].
To investigate the effect of leflunomide on the inflammatory factors and immune function of rats with chronic glomerulonephritis. Thirty rats of chronic glomerular nephritis model were established by injecting cationic bovine serum albumin (C-BSA). Rats with successfully modeled were randomly divided into model group and observation group. Another 15 rats injected with physiological saline in the same way were chosen as the control group. Modeling after 2 weeks, rats in the observation group were given leflunomide meters suspension by gavage treatment with 5 mg/(kg x d). Rats in the control group and model group were given equal volume of saline. Rats were killed after continuous intragastric for 4 weeks. The levels of serum creatinine, blood urea nitrogen, serum total cholesterol, serum albumin and 24 h urine protein were recorded. mRNA and protein levels of peripheral blood tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) were detected by RT-PCR and ELISA method. Peripheral blood T lymphocyte subsets were evaluated by flow cytometry (FCM). Compared with the control group, the levels of serum creatinine, blood urea nitrogen, serum total cholesterol, serum albumin and 24 h urine protein in model group and observation group were significantly increased (P < 0.05); Compared with the model group, these biochemical indexes in observation group decreased significantly (P < 0.05). Comparison with the control group, mRNA and protein levels of peripheral blood TNF-α and IL-6 in model group and observation group rats were significantly increased (P < 0.05). Compared with the model group, mRNA and protein levels of TNF-α and IL-6 were significantly decreased (P < 0.05). Compared with the control group, peripheral blood T lymphocyte subsets in the model group and observation group were imbalance, the difference was significant (P < 0.05). Compared with the model rats, T lymphocyte subsets in the observation group after treatment tended to be stable (P > 0.05). Leflunomide can significantly reduce the levels of biochemical indexes and inhibit the inflammatory reaction. The mechanism may be related to the regulation of immune function.


Is your document control out of control? Complying with document control regulations.
Clinical laboratories, faced with new or changing regulations and shortages in trained laboratory staff, may find it difficult to comply with guidelines related to document control, upkeep of standard operating procedure manuals, and documentation of quality programs or competency reviews. Now, more than ever, it is critical to keep documents, procedures, and training material organized and accessible to busy laboratory staff and inspectors. The key may be the ability to use existing software programs available to industry for similar compliance issues. The laboratory's ability to change and update quickly with limited staffing may depend on electronic solutions to the complexities of document control. Several software programs have merit and can be integrated into a clinical laboratory.


Regulation of insulin-like growth factor (IGF)-binding protein synthesis by insulin and IGF-I in cultured bovine fibroblasts.
Specific insulin-like growth factor-binding proteins (IGFBPs) are synthesized and secreted by bovine fibroblasts in vitro. By Western ligand blotting, three molecular forms of IGFBP were identified in conditioned medium from control cultures with mol wt (Mr) of 34,000, 28,000, and 24,000. Concentrations of these three IGFBP forms increased with time in serum-free conditioned medium without benefit of hormonal supplementation. Insulin and IGF-I were potent stimuli for IGFBP production by bovine fibroblasts, whereas bovine GH, epidermal growth factor, or steroid treatment had little or no effect. Insulin and IGF-I enhanced the production of 24,000, 28,000, and 34,000 Mr IGFBPs in a dose-dependent fashion. Moreover, addition of low nanomolar concentrations of insulin or IGF-I to bovine fibroblast cultures specifically induced the secretion of a 42,000/38,000 Mr species of IGFBP, which corresponded in size to the IGF-binding subunit of the principal 150,000 Mr IGFBP complex in serum. After stimulation with insulin or IGF-I, bovine fibroblasts (3 X 10(5) cells) secreted approximately 30 ng/24 h 42,000/38,000 Mr IGFBP. Subunits of 42,000/38,000 Mr in bovine fibroblast-conditioned medium did not form macromolecular complexes in either the absence or presence of bovine GH.


Ultrasonic Transformation of Antibiotic Molecules into a Selective Chemotherapeutic Nanodrug.
Ultrasound-based engineering of carrier-free nanodrugs by supramolecular self-assembly has recently emerged as an innovative and environmentally friendly synthetic approach. By applying high-frequency sound waves (490 kHz) in aqueous solutions, the transformation of small chemotherapeutic and antibiotic drug molecules into carrier-free nanodrugs with anticancer and antimicrobial activities was recently achieved. The transformation of the antibiotic drug molecules, i.e., doxycycline, into stable nanodrugs (~130 nm) with selective anticancer activity was achieved without requiring organic solvents, chemical agents, or surfactants. The obtained nanodrug exhibited reactive oxygen species (ROS)-mediated cytotoxicity on human breast cancer (MDA-MB 231 cells) but a negligible antiproliferative effect on healthy fibroblast cells. Imaging by super-resolution microscopy (STORM) provided insights into the intracellular trafficking and endosomal escape of the nanodrugs. Overall, these findings suggest that small antibiotic drugs can be transformed into chemotherapeutic nanodrugs with high selectivity against cancer cells.


Sympathovagal Balance and Body Shape Index in Elite and Amateur Athletes: The Relationship Unraveled.
Background Heart rate variability (HRV) is one piece among a complex network of adaptations existent in athletes that help them gain a better understanding of their own physiology. Sympathovagal balance is one of the spectral components of HRV analysis and is used to assess the frequently changing oscillations of a healthy heart, which can help in gauging the response of cardiac function towards physiological stress during exercise. This index is extensively used in appraising cardiac autonomic modulation. An evaluation of body composition in athletes has become a critical consideration when tracking HRV, as it helps practitioners understand the role of the autonomic nervous system (ANS) in obesity. The body shape index (BSI), which is based on waist circumference (WC), is an anthropometric parameter with decent predictive ability when measuring centripetal obesity. In this regard, the current study is an attempt to unravel the relationship between BSI and sympathovagal balance during exercise performed on two different instruments (treadmill and ergometer) by elite and amateur athletes. Methods It was an observational case-control study that included 30 elite and 120 amateur athletes. Symptom-limited exercise testing was performed by athletes on a motorized treadmill and ergometer in the sports physiology laboratory of a rural medical college in central India. Different anthropometric parameters like BSI and body surface area (BSA) were also recorded. Short-term HRV extracted from electrocardiogram (ECG) recordings was obtained using the Power Lab system and HRV analysis by LabChart software. Results The sympathovagal ratio, i.e., ratio of low frequency (LF) to high frequency (HF) in elite and amateur male populations showed a higher value than that in females, indicating a dominant sympathetic response in the males. There was a significant (p=0.042) positive correlation (r=0.24) between BSI and LF/HF Ratio in amateur females during treadmill exercise, whereas a significant (p=0.049) negative correlation (r=-0.27) was obtained in amateur males during ergometer exercise. Hence, increased weight and BSI were found to be associated with high sympathetic dominance, indicating a sympathovagal imbalance. Conclusion We attempted to explore the interaction between BSI and LF/HF during exercise performed on two different instruments (treadmill and ergometer) by elite and amateur athletes, which can help in testing the response of cardiac function to stress experienced during exercise. The study's uniqueness stems from discovering the relationship between BSI and HRV and how this relationship impacts sports performance. BSI measurement in athletes, both elite and amateur, allows for the assessment and forecasting of potential autonomic activity under exercise-induced stress by linking HRV with BSI.


Transition metal-free reductive coupling of allylic sulfonylhydrazones with aryl boronic acids for C(sp3)-C(sp2) bond formation.
The reductive coupling between allylic sulfonylhydrazones and aryl boronic acids gives 1,3-diarylpropene systems with good to excellent yields. Simple reaction conditions, high yields, and good functional group tolerance are the salient features of this reaction which takes place without using any transition-metal catalysts and an inert atmosphere. The substituents on aryl boronic acid or allylic sulfonylhydrazone play a role in the isomerization of the double bond. The 3,3-diphenylacrylaldehyde derived allylic sulfonylhydrazone gives almost exclusively a single isomer.


Multimodal partial volume correction: Application to [11C]PIB PET/MRI myelin imaging in multiple sclerosis.
The [11C]PIB PET tracer, originally developed for amyloid imaging, has been recently repurposed to quantify demyelination and remyelination in multiple sclerosis (MS). Myelin PET imaging, however, is limited by its low resolution that deteriorates the quantification accuracy of white matter (WM) lesions. Here, we introduce a novel partial volume correction (PVC) method called Multiresolution-Multimodal Resolution-Recovery (MM-RR), which uses the wavelet transform and a synergistic statistical model to exploit MRI structural images to improve the resolution of [11C]PIB PET myelin imaging. MM-RR performance was tested on a phantom acquisition and in a dataset comprising [11C]PIB PET and MR T1- and T2-weighted images of 8 healthy controls and 20 MS patients. For the control group, the MM-RR PET images showed an average increase of 5.7% in WM uptake while the grey-matter (GM) uptake remained constant, resulting in +31% WM/GM contrast. Furthermore, MM-RR PET binding maps correlated significantly with the mRNA expressions of the most represented proteins in the myelin sheath (R2 = 0.57 ± 0.09). In the patient group, MM-RR PET images showed sharper lesion contours and significant improvement in normal-appearing tissue/WM-lesion contrast compared to standard PET (contrast improvement > +40%). These results were consistent with MM-RR performances in phantom experiments.


Single anterior portal: A better option for arthroscopic treatment of traumatic anterior shoulder instability?
The aim of this study was to compare single and double anterior portal techniques in the arthroscopic treatment of traumatic anterior shoulder instability. A total of 91 cases who underwent arthroscopic Bankart repair for anterior shoulder instability were reviewed. The patients were divided into 2 groups as Group 1 (47 male and 2 female; mean age: 25.8 ± 6.8) for arthroscopic single anterior portal approach and Group 2 (41 male and 1 female; mean age: 25.4 ± 6.6) for the classical anterior double portal approach. The groups were compared for clinical scores, range of motion, analgesia requirement, complications, duration of surgery, cost and learning curve according to a short questionnaire completed by the relevant healthcare professionals. No statistically significant difference was found between the 2 groups in terms of pre-operative and post-operative Constant and Rowe Shoulder Scores, range of motion and complications (p > 0.05). In Group 2 patients, the requirement for post-operative analgesics was significantly higher (p < 0.001), whereas the duration of surgery was statistically significantly shorter in Group 1 (p < 0.001). In the assessment of the questionnaire, it was seen that a single portal anterior approach was preferred at a higher ratio (p = 0.035). The cost analysis revealed that the cost was 5.7% less for patients with a single portal. In the arthroscopic treatment of traumatic anterior shoulder instability accompanied by a Bankart lesion, the anterior single portal technique is as successful in terms of clinical results as the conventional double portal approach. The single portal technique has advantages such as less postoperative pain, a shorter surgical learning curve and lower costs. Level III, Therapeutic study.


Comparison of GHG emissions from annual crops in rotation on drained temperate agricultural peatland with production of reed canary grass in paludiculture using an LCA approach.
Drained peat soils contribute significantly to global human-caused CO2 emissions and reducing peat degradation via rewetting is high on the political agenda. Ceasing agricultural activities on rewetted soils might lead to land owner resistance and high societal expenses to compensate farmers. Continued biomass production adapted for wet conditions on peat soils potentially minimizes these costs and helps supplying the growing demand for e.g. materials, fuels and feed. Here we used a life cycle assessment approach (cradle to farm gate) to investigate the greenhouse gas (GHG) emissions related to three cases by applying IPCC (Intergovernmental Panel on Climate Change) emission factors and specific site conditions at a bog and a fen site that represent widely distributed temperate peat soils. Besides soil emissions, upstream emissions from input, operational emissions and emission related to rewetting construction work were included. The analyzed systems were deeply drained cash cropping on agricultural bog (potatoes (Solanum tuberosum L.), spring barley (Hordeum vulgare L.) and oat (Avena sativa L.), permanent Reed canary grass (RCG) (Phalaris arundinacea L.) production on non-drained bog and permanent RCG production on shallow-drained fen. The annual mean water table depths (WTD) were -70, -38 (estimated) and -13 cm, respectively. Results showed estimated GHG emissions of 40.5, 26.1 and 20.6 Mg CO2eq ha-1, respectively, corresponding to a 35% GHG reduction for the non-drained bog case as compared to the drained bog case, despite that the obtained WTD due to ceased drainage did not adhere to the IPCC rewetting threshold of -30 cm. Emissions related to crop management represented 7, 14 and 19% of total emissions. In the RCG cultivation on fen case, the WTD were controlled primarily by the water table of the nearby stream and total GHG emissions were even lower as compared to the RCG production on the non-drained bog reflecting the difference in WTD. Rewetting projects need to include careful knowledge of the specific peat area to foresee the actual reduction potential.


Alcohol disorders among patients with burns: crisis and opportunity.
A burn injury so severe that inpatient treatment is necessary is a crisis in any patient's life. For patients who also suffer from an alcohol use disorder, hospitalization may offer a unique opportunity to facilitate entry into appropriate treatment. In this study, 442 hospitalized patients with burns were evaluated, and 50 (11%) were diagnosed with an alcohol use disorder by DSM-III-R criteria. All but one of the injuries were deemed preventable. The average length of stay in hospital was 9 days longer for the alcohol group compared with the average stay in the burn center, resulting in additional costs of $337,500. Referral for treatment of the underlying alcohol disorder was recommended for fewer than half the patients. Thus, although the patients with alcohol use disorders had lengthy hospitalizations and were in circumstances that might permit the characteristic denial of alcoholism to be relinquished, the treatment team usually did not capitalize on this opportunity.


Reversal of the sleep-wake cycle by heroin self-administration in rats.
The goal of this study was to examine how heroin self-administration, abstinence, and extinction/reinstatement affect circadian sleep-wake cycles and the associated sleep architecture. We used electroencephalography (EEG) and electromyography (EMG) to measure sleep patterns in male Sprague-Dawley rats over 16 trials of heroin self-administration (acquisition), 14 days of abstinence, and a single day of extinction and drug-induced reinstatement. Rats self-administering heroin showed evidence of reversed (diurnal) patterns of wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep throughout acquisition. During abstinence, their wake and NREM sleep patterns were immediately restored to the normal nocturnal distribution. REM patterns remained inverted for the first 3-6 days of abstinence in heroin self-administering rats. The single extinction/reinstatement test was without effect. These data suggest that heroin may have the ability to affect circadian distribution of sleep and wakefulness, either indirectly, where animals shift their sleep-wake cycle to allow for drug taking, or directly, through wake-promoting actions or actions at circadian oscillators in the brain.


Design and implementation of clinical trials of antimicrobial drugs and devices used in periodontal disease treatment.
The design and implementation of clinical trials (CTs) carried out to evaluate antimicrobial and anti-infective drugs and devices are one of the most difficult challenges in contemporary periodontal research and product development. The overwhelming amount of evidence which has established a microbial etiology for periodontitis is the basis for developing and testing antimicrobial treatments. Well-designed antimicrobial CTs start with a carefully crafted hypothesis and a protocol which explicitly integrates the requirements of the patient, the clinician, the sponsor, and regulatory authorities. Surrogate variables for effectiveness must be clinically relevant, scientifically sound, and statistically valid. Currently, clinical attachment level measurements and alveolar bone assessments are accepted as proof of effectiveness. Indication and claim support of the antimicrobial product guide the design and implementation of the CT. Adverse microbiologic consequences, such as lack of antimicrobial susceptibility, wrong spectrum, incorrect dosage, non-compliance, and drug interference, must be monitored. Successful CTs balance a large group of variables used to screen, randomize, and assign subjects to experimental and control groups to ensure that prognostic and risk factors are properly accounted for.


miR-285-Yki/Mask double-negative feedback loop mediates blood-brain barrier integrity in Drosophila.
The Hippo signaling pathway is highly conserved from Drosophila to mammals and plays a central role in maintaining organ size and tissue homeostasis. The blood-brain barrier (BBB) physiologically isolates the brain from circulating blood or the hemolymph system, and its integrity is strictly maintained to perform sophisticated neuronal functions. Until now, the underlying mechanisms of subperineurial glia (SPG) growth and BBB maintenance during development are not clear. Here, we report an miR-285-Yorkie (Yki)/Multiple Ankyrin repeats Single KH domain (Mask) double-negative feedback loop that regulates SPG growth and BBB integrity. Flies with a loss of miR-285 have a defective BBB with increased SPG ploidy and disruptive septate junctions. Mechanistically, miR-285 directly targets the Yki cofactor Mask to suppress Yki activity and down-regulates the expression of its downstream target cyclin E, a key regulator of cell cycle. Disturbance of cyclin E expression in SPG causes abnormal endoreplication, which leads to aberrant DNA ploidy and defective septate junctions. Moreover, the expression of miR-285 is increased by knockdown of yki or mask and is decreased with yki overexpression, thus forming a double-negative feedback loop. This regulatory loop is crucial for sustaining an appropriate Yki/Mask activity and cyclin E level to maintain SPG ploidy and BBB integrity. Perturbation of this signaling loop, either by dysregulated miR-285 expression or Yki activity, causes irregular SPG ploidy and BBB disruption. Furthermore, ectopic expression of miR-285 promotes canonical Hippo pathway-mediated apoptosis independent of the p53 or JNK pathway. Collectively, these results reveal an exquisite regulatory mechanism for BBB maintenance through an miR-285-Yki/Mask regulatory circuit.


Herbivore exclusion drives the evolution of plant competitiveness via increased allelopathy.
The 'Evolution of Increased Competitive Ability (EICA)' hypothesis predicts the evolution of plant invasiveness in introduced ranges when plants escape from their natural enemies. So far, the EICA hypothesis has been tested by comparing plant vigor from native and invasive populations, but these studies are confounded by among-population differences in additional environmental factors and/or founder effects. We tested the major prediction of EICA by comparing the competitive ability (CA) of Solidago altissima plants originating from artificial selection plots in which we manipulated directly the exposure to above-ground herbivores. In a common garden experiment, we found an increase in inter-specific, but not intra-specific, CA in clones from herbivore exclusion plots relative to control plots. The evolutionary increase in inter-specific CA coincided with the increased production of polyacetylenes, whose major constituent was allelopathic against a heterospecific competitor, Poa pratensis, but not against conspecifics. Our results provide direct evidence that release from herbivory alone can lead to an evolutionary increase in inter-specific CA, which is likely to be mediated by the increased production of allelopathic compounds in S. altissima.


Weapon performance, not size, determines mating success and potential reproductive output in the collared lizard (Crotaphytus collaris).
In territorial polygynous taxa, reproductive success reflects phenotypic variation. Using Crotaphytus collaris, a sexually dimorphic lizard in which males use the head (i.e., jaws and associated musculature) as a weapon when territorial interactions escalate to fights, we tested the hypothesis that weapon performance (i.e., bite force) is a better predictor of fitness than body or weapon size. Bite-force performance predicted the number of female home ranges overlapped, estimated mating success, and potential reproductive output. However, no body or weapon size measure correlated with these estimates of fitness, and only one weapon dimension (head width) correlated with bite force. These results indicate that weapon performance has far stronger effects on fitness than body or weapon size, likely because it directly influences fight outcomes. As such, it is desirable that the use of morphology as a proxy for performance and its presumed extensions to fitness be based on empirical morphology-performance relationships.


Peer Rejection and Perceived Quality of Relations With Schoolmates Among Children With ADHD.
The main aim of the current study was to investigate the links between ADHD diagnosis and the objective and subjective dimensions of social relationships among children from primary schools. We used the data from 36 regular classrooms, consisting of 718 students, with each containing at least one child with an established clinical diagnosis of ADHD (38 children). For children with ADHD, the level of the perceived quality of social relations was lower than that of children without such a diagnosis. After controlling for sociometric status, the impact of ADHD on perceived status proved to be statistically nonsignificant but the indirect impact of ADHD on this status through sociometric status was statistically significant. Children diagnosed with ADHD are more often rejected by their peers and have a more pessimistic view of their social world. Moreover, ADHD diagnosis does not have a direct influence on the perceived quality of social relations otherwise than through sociometric status.


[Research advances in antitumor activities of pyrimidine derivatives].
Pyrimidine derivatives have been the subject of much attention in pesticide and medicine fields owing to their unique biological properties. Particularly, a large number of these compounds have recently been reported to show substantial antitumor activities, and some of them have been investigated in clinical trials. Although these structurally novel compounds have a common chemical moiety of a pyrimidine ring, there are a variety of mechanisms of their antitumor action, such as, inhibition of cyclin-dependent-kinases, inhibition of protein tyrosine kinase, inhibition of carbonic anhydrases, inhibition of dihydrofolate reductase and disruption of microtubule assembly. In this paper, we described the latest advances in the research of such pyrimidine derivatives as antitumor drug according to their action on targets.


Food-additive-induced urticaria: a survey of 838 patients with recurrent chronic idiopathic urticaria.
Recurrent chronic idiopathic urticaria (RCIU) is a common skin condition that affects 0.1-3% of the population in the USA and Europe and accounts for nearly 75% of all 'ordinary' chronic urticaria (CU) cases. We studied 838 consecutive patients with RCIU referred to hospital between 1998 and 2003. Patients with known causes of CU were excluded. Clinical history, physical examination, and symptom diaries were evaluated during two periods, a diet-free period (1 week) and a food-additive-free diet (FAFD) period (4 weeks), respectively, and two double-blind placebo-controlled (DBPC) challenges of six food additives were administered. The first DBPC challenge included a mixture of the six food additives (DBPCmixed) given to all patients. The second DBPC challenge comprised the single food additives, administered at increasing doses (DBPCsingle) to patients with a positive DBPCmixed test and 105 patients with a negative DBPCmixed test, as a control. The DBPCmixed challenge was positive in 116 patients. None of the 105 control patients had a positive DBPCsingle test. Only 31 DBPCsingle tests were positive in patients with positive DBPCmixed challenge. Twenty-four of the 116 patients showing a positive DBPCmixed challenge also had a positive DBPCsingle result. Our results confirmed that food additive hypersensitivity reactions occurred in few RCIU patients using DBPCsingle challenge. The combination of the results of FAFD and DBPCmixed challenge seems to be of considerable practical interest for allergists, internists and dermatologists, rather than the data of clinical history and the results of DBPCsingle challenge, in patients with RCIU.


First-principles predictions for shear viscosity of air components at high temperature.
The direct molecular simulation (DMS) method is used to obtain shear viscosity data for non-reacting air and its components by simulating isothermal, plane Poiseuille subsonic flows. Shear viscosity is estimated at several temperatures, from 273 K to 10 000 K, by fitting the DMS velocity profiles using the analytic solution of the Navier-Stokes equations for this simple canonical flow. The ab initio potential energy surfaces (PESs) that describe the various atomic-level interactions are the only input in the simulations. Molecules involved in a collision within the flow can occupy any rovibrational state that is allowed by the effective diatomic potential. For molecular nitrogen, oxygen, and air at standard condition molar composition, the DMS shear viscosity predictions are in excellent agreement with the experimental data that are available up to about 2000 K. The results for pure molecular nitrogen and pure molecular oxygen also agree very well with previously published quasi-classical trajectory (QCT) calculations based on the same PESs. It is further shown that the ab initio shear viscosity data are generally lower than the corresponding values used in popular computational fluid dynamics codes, over a wide temperature range. Finally, Wilke's mixing rule is demonstrated to accurately predict the DMS air viscosity results from the pure molecular components data up to 4000 K.


Coexpression of NUP98/TOP1 and TOP1/NUP98 in de novo Acute Myeloid Leukemia with t(11;20)(p15;q12) and t(2;5)(q33;q31).
The t(11;20)(p15;q11∼12) translocation is a very rare but recurrent cytogenetic aberration that occurs in myelodysplastic syndrome/acute myeloid leukemia (MDS/AML). This translocation was shown to form a fusion gene between NUP98 at 11p15 and TOP1 at 20q12. Here, we describe a new case of de novo AML M2 with t(11;20) which was associated with another balanced translocation. An 81-year-old man was admitted to undergo salvage therapy for relapsed AML. G-banding and spectral karyotyping showed 46,XY,t(2;5)(q33;q31),t(11;20)(p15;q12)[20]. Expression of the NUP98/TOP1 fusion transcript was confirmed: NUP98 exon 13 was in-frame fused with TOP1 exon 8. The reciprocal TOP1/NUP98 fusion transcript was also detected: TOP1 exon 7 was fused with NUP98 exon 14. After achieving hematological complete remission, the karyotype converted to 46,XY,t(2;5)(q33;q31)[19]/46,sl,t(11;20)(p15;q12)[1]. FISH analysis demonstrated that the 5q31 breakpoint of t(2;5) was centromeric to EGR1. In all 10 cases described in the literature, the NUP98 exon 13/TOP1 exon 8 fusion transcript was expressed, indicating that it may be responsible for the pathogenesis of MDS/AML with t(11;20). On the other hand, the TOP1/NUP98 transcript was coexpressed in 4 cases of de novo AML, but not in 3 cases of therapy-related MDS. Thus, this reciprocal fusion may be associated with progression to AML.


Triangular tapered duodenoplasty for the treatment of congenital duodenal obstruction.
To evaluate the safety and efficiency of triangular tapered duodenoplasty, a modified procedure for the treatment of congenital duodenal obstruction was designed. Eight children underwent triangular tapered duodenoplasty over a 5-year period with a minimum follow-up of 27-months. Study parameters include morbidity and mortality postsurgical time to feedings, hospital length of stay, and weight gain. In addition, all patients were asked to undergo postoperative gastric emptying scans and upper gastrointestinal series (UGIS). Eight children underwent triangular tapered duodenoplasty with 0% surgical morbidity and mortality rates. Mean postsurgical time to feedmap was 5.7 days (range, 2 to 12 days), and mean hospital length of stay was 9.6 days (range, 4 to 15 days). Mean NCHS weight gain was 50% (range, 25% to 75%). Five patients underwent postoperative gastric emptying scans with a mean Tc 43 minutes (range, 24 to 70 minutes; normal, 50 minutes). Four patients underwent postoperative UGIS showing no evidence of megaduodenum in any patient. Triangular tapered duodenoplasty is safe and effective in the treatment of congenital duodenal obstruction. The morbidity and mortality rates and hospital stay resulting from this procedure are the lowest as yet reported in the medical literature.


Restriction fragment length polymorphisms in HLA-DR4-DQ3 haplotypes associated with rheumatoid arthritis.
Restriction fragment length polymorphism (RFLP) patterns were studied in serologically confirmed DR4-DQ3 positive patients with rheumatoid arthritis by Southern blot analysis using full length cDNA probes specific for DRB, DQA and DQB hybridized with genomic DNA digested with informative restriction endonucleases. The RFLP patterns correlated with serology confirming all patients to be DR4+ve. The DQB1*0302 (DQ8) allele identified by 12.0kb BamHI, 3.3kb Hind III and 1.8kb Taql fragments was present in all patients suggesting them to be DR4-DQB1*0302. Hybridization of Taq 1 and PVU II digested genomic DNA with DQA cDNA probe revealed four informative RFLP patterns. While three of them correlated with known DR4 subtypes, one was a new polymorphism observed specifically in Indian patients with rheumatoid arthritis. The study further indicated that two of the several known subtypes of DR4, viz., DRB1*0401-DW4-DQB1*0302 and DRB1*0404-DW14-DQB1*0302 may be implicated in susceptibility to rheumatoid arthritis in the Indian population.


Gut Microbiome and Bile Acid Metabolism Induced the Activation of CXCR5+ CD4+ T Follicular Helper Cells to Participate in Neuromyelitis Optica Spectrum Disorder Recurrence.
From the perspective of the role of T follicular helper (Tfh) cells in the destruction of tolerance in disease progression, more attention has been paid to their role in autoimmunity. To address the role of Tfh cells in neuromyelitis optica spectrum disorder (NMOSD) recurrence, serum C-X-C motif ligand 13 (CXCL13) levels reflect the effects of the Tfh cells on B-cell-mediated humoral immunity. We evaluated the immunobiology of the CXCR5+CD4+ Tfh cells in 46 patients with NMOSD, including 37 patients with NMOSD with an annual recurrence rate (ARR) of<1 and 9 patients with NMOSD with an ARR of ≥1. Herein, we reported several key observations. First, there was a lower frequency of circulating Tfh cells in patients with an ARR of<1 than in those with an ARR of ≥1 (P< 0.05). Second, the serum CXCL13 levels were downregulated in individuals with an ARR<1 (P< 0.05), processing the ability to promote Tfh maturation and chemotaxis. Third, the level of the primary bile acid, glycoursodeoxycholic acid (GUDCA), was higher in patients with NMOSD with an ARR of<1 than in those with NMOSD with an ARR of ≥1, which was positively correlated with CXCL13. Lastly, the frequency of the Tfh precursor cells decreased in the spleen of keyhole limpet haemocyanin-stimulated animals following GUDCA intervention. These findings significantly broaden our understanding of Tfh cells and CXCL13 in NMOSD. Our data also reveal the potential mechanism of intestinal microbiota and metabolites involved in NMOSD recurrence.


Drug-induced liver injury: hepatotoxicity of quetiapine revisited.
Drug hepatotoxicity is the most common cause of fulminant hepatic failure in the USA. We describe a rare case of a patient who developed an acute liver injury after initiation of therapy with quetiapine, but after conservative management and a trial of steroids, has fully recovered. This is the second reported case of quetiapine-induced liver injury in the published literature.


Population-based cohort of 500 patients with Gaucher disease in Israel.
To characterise a population-based cohort of patients with Gaucher disease (GD) in Israel relative to the general population and describe sociodemographic and clinical differences by disease severity (ie, enzyme replacement therapy [ERT] use). A cross-sectional study was conducted. Data from the Clalit Health Services electronic health record (EHR) database were used. The study population included all patients in the Clalit EHR database identified as having GD as of 30 June 2014. A total of 500 patients with GD were identified and assessed. The majority were ≥18 years of age (90.6%), female (54.0%), Jewish (93.6%) and 34.8% had high socioeconomic status, compared with 19.0% in the general Clalit population. Over half of patients with GD with available data (51.0%) were overweight/obese and 63.5% had a Charlson Comorbidity Index ≥1, compared with 46.6% and 30.4%, respectively, in the general Clalit population. The majority of patients with GD had a history of anaemia (69.6%) or thrombocytopaenia (62.0%), 40.4% had a history of bone events and 22.2% had a history of cancer. Overall, 41.2% had received ERT. Establishing a population-based cohort of patients with GD is essential to understanding disease progression and management. In this study, we highlight the need for physicians to monitor patients with GD regardless of their ERT status.


Hospital costs and clinical characteristics of continuous renal replacement therapy patients: a continuous ethical dilemma.
This study describes the clinical characteristics and examines hospital costs involved in the care of 117 patients undergoing Continuous Renal Replacement Therapy (CRRT) between January 1999 and August 2002. The majority (70.9%) of the patients undergoing CRRT expired in the hospital. Statistically significant differences were found with respect to the length of stay for discharge status and gender; and with respect to costs for surgery versus no surgery and gender. Significant differences were also found between discharge status and gender, age, and cardiovascular surgery. The results of this study raise economic and ethical questions related to the cost/benefit of CRRT and the futility of the treatment. Hospitals should ensure that they have utilization protocols in place for CRRT, promote cooperation between intensive care unit (ICU) physicians and nephrologists, and create multi-disciplinary CRRT teams in an effort to maximize the effectiveness of therapy and minimize costs.


Characterization of particulate and soluble variants of the brush-border enzymes alanine aminopeptidase, alkaline phosphatase and gamma-glutamyltransferase in human urine.
The urinary brush-border enzymes alanine aminopeptidase, alkaline phosphatase and gamma-glutamyltransferase can be separated by ultracentrifugation into a particulate and a soluble fraction. These variants have been characterized with respect to their kinetic data, heat stability, electrophoretic mobility and behaviour in gel chromatography and affinity chromatography. Both variants of these enzymes show nearly identical Km values and activity curves as functions of rho H and substrate concentration. The particulate variant is more heat-sensitive than the soluble one. The soluble variant as well as the particulate form consist of one fraction bound by Con A-sepharose and another one unbound by it. Origins and nature of these multiple variants in connection with their possible diagnostic significance are discussed.


Crack Size and Undermatching Effects on Fracture Behavior of a Welded Joint.
Crack size and undermatching effects on fracture behavior of undermatched welded joints are presented and analyzed. Experimental and numerical analysis of the fracture behavior of high-strength low-alloyed (HSLA) steel welded joints with so-called small and large crack in undermatched weld metal and the base metal was performed, as a part of more extensive research previously conducted. J integral was determined by direct measurement using special instrumentation including strain gauges and a CMOD measuring device. Numerical analysis was performed by 3D finite element method (FEM) with different tensile properties in BM and WM. Results of J-CMOD curves evaluation for SUMITEN SM 80P HSLA steel and its weld metal (WM) are presented and analyzed for small and large cracks in tensile panels. This paper is focused on some new numerical results and observations on crack tip fields and constraint effects of undermatching and crack size keeping in mind previously performed experiments on the full-scale prototype. In this way, a unique combined approach of experimental investigation on the full-scale proto-type and tensile panels, as well as numerical investigation on mismatching and crack size effects, is achieved.


Implantable Cardiovascular Devices: Current and Emerging Technologies for Remote Heart Failure Monitoring.
Heart failure remains a substantial socioeconomic burden to our health care system. With the aging of the population, the incidence is expected to rise in the ensuing years. Standard heart failure management strategies have failed to reduce hospitalizations and mortality. In patients with heart failure, remote hemodynamic monitoring with implantable devices provides essential data, which can be used in unison with standard patient management to reduce heart failure hospitalizations. This review will chronicle the important clinical trials of various implantable devices and describe the emerging technologies in remote heart failure management. Cardiovascular implantable electronic devices, namely implanted cardioverter-defibrillator and cardiac resynchronization therapy devices with defibrillator, have evolved beyond sole resynchronization and currently can deliver real-time cardiac hemodynamics. Clinical data regarding hemodynamic monitoring with implanted cardioverter-defibrillator and cardiac resynchronization therapy devices with defibrillator have not consistently demonstrated a reduction in heart failure or mortality benefit. However, there is promise in the future with the application of multiparameter diagnostic algorithms with these devices. The most efficacious implantable device has been the pulmonary artery pressure sensor, CardioMEMS. This device has been proven to be safe and shown to reduce heart failure hospitalizations. Moreover, multiple newly developed devices are currently under investigation after successful first-in-man studies.


Nonvolatile Memories Based on Graphene and Related 2D Materials.
The pervasiveness of information technologies is generating an impressive amount of data, which need to be accessed very quickly. Nonvolatile memories (NVMs) are making inroads into high-capacity storage to replace hard disk drives, fuelling the expansion of the global storage memory market. As silicon-based flash memories are approaching their fundamental limit, vertical stacking of multiple memory cell layers, innovative device concepts, and novel materials are being investigated. In this context, emerging 2D materials, such as graphene, transition metal dichalcogenides, and black phosphorous, offer a host of physical and chemical properties, which could both improve existing memory technologies and enable the next generation of low-cost, flexible, and wearable storage devices. Herein, an overview of graphene and related 2D materials (GRMs) in different types of NVM cells is provided, including resistive random-access, flash, magnetic and phase-change memories. The physical and chemical mechanisms underlying the switching of GRM-based memory devices studied in the last decade are discussed. Although at this stage most of the proof-of-concept devices investigated do not compete with state-of-the-art devices, a number of promising technological advancements have emerged. Here, the most relevant material properties and device structures are analyzed, emphasizing opportunities and challenges toward the realization of practical NVM devices.