Catastrophic visceral involvement secondary to de novo systemic vasculitis in a renal transplant recipient.
De novo systemic vasculitis after renal transplant is a rare complication. We report a patient who developed rapid, catastrophic necrotizing vasculitis of the gastrointestinal tract 11 months after renal transplant. A 60-year-old man was admitted for persistent pain in the right abdomen and mild intestinal hemorrhage. After some days the patient presented partial intestinal occlusion, severe hypoproteinemia and acute renal insufficiency. The patient was urgently operated with resection of a tract of the jejunum where there was a venous infarct. Laboratory tests were not significant and the search for hepatitis B, C viruses and ANCA was negative. After some days of irrepressible intestinal hemorrhage, total gastrectomy, splenectomy and resection of the duodenum and pancreas were performed. Histological pictures showed vascular lesions pathognomonic of systemic polyarteritis nodosa (PAN). After thirty days the patient died. The autopsy confirmed atypical systemic PAN with involvement of the pulmonary arteries besides the gastrointestinal tract and pancreas. Gastrointestinal (GI) complications are not frequent in renal transplant recipients, but 30% of patients with such lesions die as a direct consequence of visceral vascular damage. To the best of our knowledge, de novo PAN has been reported as the cause of catastrophic gastrointestinal involvement in only one renal transplant recipient. This case therefore raises the number of reports of PAN in kidney transplantation recipients who had no history of underlying connective tissue disease.


[Goethe's philosophical-medical masks, in Faust].
At the beginning of the XXI century the health profession is engaged in a medical ethical and moral crisis and society, hurt by the pandemic of violence and impunity, feels the effect of a state of legal crisis unable to find a viable scientific or humanistic answer. This manuscript, is the result of an investigation into the Johann Wolfgang Goethe's tragedy of the nineteenth century, Faust. It demonstrates the coincidence of real life subjects and objects with literary subjects and objects represented, by means of the interpretation of the paradigms, problems, dilemmas and identified cases of medical ethical-morals: dáimon, reflection-solitude, free will, good-evil, Eros, learned ignorance, genes, epistemology, medical etiquette, paternalism, anatomy of the personality, Hyppocratism, will, good sense of humor, bubonic plague. Faust can be construed as a new path for change--towards the common good--of the physician if traced by their will and recovering the represented real objects, decides to meditate free and lonely on its professional exercise, medical knowledge and the doctor-patient relationship.


Diagnosis and treatment of psychiatric comorbidity in a patient with charles bonnet syndrome.
Background. A significant proportion of patients with neurological disorders may have comorbid psychiatric symptomology, which may be managed by primary outpatient neurologists. Referral to their psychiatric colleagues is mediated by available consultation-liaison units and according to clinical opinion. Aims of Case Report. We present the case of a patient whose initial referral to epilepsy clinic led to a workup which ultimately diagnosed her with nonepileptic seizures (NES). In the course of her follow-up, she developed intractable headaches, and worsening mood symptoms and eventually exhibited Psychotic Features for which psychiatry became coinvolved in her care. Major Depression with Psychotic Features and Charles Bonnet syndrome were considered as a likely comorbid diagnoses. Her pharmacologic management on venlafaxine and quetiapine eventually caused substantial amelioration of her psychiatric symptomology as longitudinally followed by PHQ-9 and GAD-7 scores. Conclusion. Optimal evaluation and management of mental illness in patients with complex neurologic symptomology may require independent evaluation and treatment by psychiatrists when clinically appropriate.


A lower level of entropy in circadian rhythm of the sinus R-R intervals suggests a prevalence of the cardiac sympathetic regulation in early physiological pregnancy.
The study estimates the unpredictable disorder (chaos) within the 24 h pattern of sinus R-R intervals (SRRI) in clinically healthy pregnant women (CHPW) and clinically healthy non-pregnant women (CHNPW), in order to evaluate the early gestational changes in neurovegetative cardiac pacing. SRRI were provided by the 24-h Holter ECG of 10 CHPW and 10 CHNPW. SRRI were investigated by descriptive conventional statistics by means of the Time and Frequency Domain Analysis, and subsequently, in their chaotic component by means of entropy analysis. Both the SRRI and entropy were tested via the Cosinor method to better decipher whether or not the periodic disorder in heart rate variability is modified in pregnancy as a result of a gestational tonic resetting of the cardiac sympatho-vagal regulation. Cosinor analysis documented that the circadian rhythm of both the SRRI and entropy were preserved in CHNPW and CHPW. However, the circadian rhythm of SRRI and entropy in CHPW exhibited a significantly decreased 24 h mean. Via the analysis of the rhythmicity of entropy, this study has documented that the chaos in the 24 h pattern of SRRI is less prominent in CHPW than in CHNPW. Such a reduction of level in the deterministic periodic chaos of heart rate variability provides evidence that, in early pregnancy, a tonic elevation of the sympathetic activity regulates cardiac pacing.


Emergency contraceptive pill use among women in Denmark, Norway and Sweden: Population-based survey.
Emergency contraceptive pill (ECP) use is reported to have increased in several countries over time. In this multi-country population-based questionnaire study, we aimed to describe the patterns of ECP use and identify factors associated with its use. In 2011-2012, women aged 18-45 years were randomly selected from national registers in Denmark, Norway and Sweden and invited to respond to questions related to lifestyle and contraceptive use. We used generalized logistic models to estimate odds ratios (ORs) and 95% confidence intervals (CI) comparing women who had used ECP with women who had never used ECP. Of the 45 445 women, 33.9% (Denmark = 32.3%, Norway = 35.1%, Sweden = 34.6%) had used ECP at least once in their lifetime. Among ECP users, 15.8% had used ECP within the last year and 50.0% had used ECP more than once in their life. After adjusting for country, age at response and response type, ECP use was associated with higher education (OR 2.09, 95% CI 1.54-2.84) and being single, divorced or widowed (OR 3.17, 95% CI 2.87-3.49). Binge drinking and smoking increased the odds of ECP use. Furthermore, early age at first intercourse (OR 1.29, 95% CI 1.08-1.55), having a new partner in the last 6 months (≥3 partners: OR 6.44, 95% CI 5.46-7.60) and lack of condom use with a recent new partner (OR 1.42, 95% CI 1.22-1.66) were found to be associated with ECP use. Our study shows that ECP use is common among Scandinavian women. Higher education and being single were associated with increased odds of ECP use. Risk behaviors such as smoking and early age at first sex were also associated with increased odds of ECP use. Since ECP use is not protective against sexually transmitted infections, our findings highlight the need to encourage awareness and regular use of condoms to prevent sexually transmitted diseases in women.


Periodontal disease and FAM20A mutations.
Enamel-renal-gingival syndrome (ERGS; OMIM #204690), a rare autosomal recessive disorder caused by mutations in FAM20A, is characterized by nephrocalcinosis, nephrolithiasis, amelogenesis imperfecta, hypoplastic type, gingival fibromatosis and other dental abnormalities, including hypodontia and unerupted teeth with large dental follicles. We report three patients and their families with findings suggestive of ERGS. Mutation analysis of FAM20A was performed in all patients and their family members. Patients with homozygous frameshift and compound heterozygous mutations in FAM20A had typical clinical findings along with periodontitis. The other had a novel homozygous missense mutation in exon 10, mild gingival fibromatosis and renal calcifications. The periodontitis in our patients may be a syndrome component, and similar findings in previous reports suggest more than coincidence. Fam20a is an allosteric activator that increases Fam20c kinase activity. It is hypothesized that lack of FAM20A activation of FAM20C in our patients with FAM20A mutations might have caused amelogenesis imperfecta, abnormal bone remodeling and periodontitis. Nephrocalcinosis appears not to be a consistent finding of the syndrome and the missense mutation may correlate with mild gingival fibromatosis. Here we report three patients with homozygous or compound heterozygous mutations in FAM20A and findings that extend the phenotypic spectrum of this disorder, showing that protein truncation is associated with greater clinical severity.


Transpyloric versus gastric tube feeding for preterm infants.
Enteral feeding tubes for preterm infants may be placed in the stomach (gastric tube feeding) or in the upper small bowel (transpyloric tube feeding). There are potential advantages and disadvantages to both routes. To determine the effect of feeding via the transpyloric route versus feeding via the gastric route on feeding tolerance, growth and development, and adverse consequences (death, gastro-intestinal disturbance including necrotising enterocolitis, aspiration pneumonia, chronic lung disease, pyloric stenosis) in preterm infants. We used the standard search strategy of the Cochrane Neonatal Review Group. This included searches of the Cochrane Central Register of Controlled Trials (The Cochrane Library 2012, Issue 3), MEDLINE, EMBASE, and CINAHL (to June 2012), conference proceedings, and previous reviews. Randomised or quasi-randomised controlled trials comparing transpyloric with gastric tube feeding in preterm infants. We extracted data using the standard methods of the Cochrane Neonatal Review Group with separate evaluation of trial quality and data extraction by two review authors. We synthesised data using a fixed-effect model and reported typical risk ratio (RR), risk difference (RD), and mean difference (MD). We found nine eligible trials in which a total of 359 preterm infants participated. All of the trials contained methodological weaknesses with lack of allocation concealment, absence of blinding of caregivers or assessors, and incomplete follow-up being the major potential sources of bias. The included trials did not detect any statistically significant effects on feeding tolerance or in-hospital growth rates. Meta-analyses found that infants allocated to receive transpyloric feeding had a higher risk of gastro-intestinal disturbance (typical RR 1.48 (95% confidence interval (CI) 1.05 to 2.09); typical RD 0.09 (95% CI 0.02 to 0.17); number needed to treat for an additional harmful outcome (NNTH) 10 (95% CI 6 to 50); six studies, 245 infants) and all-case mortality (typical RR 2.46 (95% CI 1.36 to 4.46); typical RD 0.16 (95% CI 0.07 to 0.26); NNTH 6 (95% CI 4 to 14); six studies, 217 infants). However, the trial that contributed most weight to these findings was likely to have been affected by selective allocation of the less mature and sicker infants to transpyloric feeding. We did not find any statistically significant differences in the incidence of other adverse events, including necrotising enterocolitis, intestinal perforation, and aspiration pneumonia. The available data do not provide evidence of any beneficial effect of transpyloric feeding for preterm infants. Some evidence of harm exists, including a higher risk of gastrointestinal disturbance and mortality, but these findings should be interpreted and applied cautiously because of methodological weaknesses in the included trials.


[Management of chronic ulcers: punch grafting].
Chronic ulcers are a common but important dermatological problem and a major source of expense in the western countries. Skin graft is a surgical procedure in which skin or skin substitute is transplanted in order to close a wound. This article aims to review the different categories of grafts, their indications for the healing of chronic ulcers of the lower limbs, emphasizing the position of punch grafts in the treatment arsenal.


Azide-Free Synthesis of N-Alkyliminophosphoranes from Phosphines and Hydroxylamine Derivatives.
A broadly applicable and efficient method for the synthesis of N-alkyliminophosphoranes from phosphines that does not use potentially hazardous alkyl azides is reported. Under iron catalysis, a hydroxylamine-derived triflic acid salt oxidizes phosphines to a wide range of iminophosphorane triflic acid salts. Diphosphines afford phosphine-iminophosphoranes that can serve as ligands in transition metal complexes. The developed method can be employed in the synthesis of mixed diiminophosphoranes and in a traceless Staudinger ligation.


[Investigations on the red blood cell count in mother sows].
Investigations have been conducted to the factors which have influence on the red blood count in postparturient sows. 147 blood samples of sows have been collected for the analysis of the influence of the number of lactations and puerperal diseases and 87 samples out of the collected blood samples were of healthy sows used to the analysis for the influence of the week of lactation. With rising number of lactations decrease the number of erythrocytes, packed cell volume and haemoglobin concentration, whereas mean corpuscular volume and mean corpuscular haemoglobin concentration rise. No significant changes of red blood count occur in the course of lactation. The number of erythrocytes and the packed cell volume decrease due to puerperal diseases. Hematological values of healthy postparturient sows are: erythrocytes: 5.8 +/- 0.6 T/l; packed cell volume: 0.41 +/- 0.03 l/l; hemoglobin concentration: 7.64 +/- 0.67 mmol/l; mean corpuscular volume: 71.4 +/- 5.8 fl; mean corpuscular hemoglobin: 1.30 +/- 0.9 fmol; mean corpuscular hemoglobin concentration: 18.3 +/- 0.8 mmol/l.


CK2 Is a component of the KSR1 scaffold complex that contributes to Raf kinase activation.
Kinase Suppressor of Ras (KSR) is a molecular scaffold that interacts with the core kinase components of the ERK cascade, Raf, MEK, and ERK and provides spatial and temporal regulation of Ras-dependent ERK cascade signaling. In this report, we identify the heterotetrameric protein kinase, casein kinase 2 (CK2), as a new KSR1-binding partner. Moreover, we find that the KSR1/CK2 interaction is required for KSR1 to maximally facilitate ERK cascade signaling and contributes to the regulation of Raf kinase activity. Binding of the CK2 holoenzyme is constitutive and requires the basic surface region of the KSR1 atypical C1 domain. Loss of CK2 binding does not alter the membrane translocation of KSR1 or its interaction with ERK cascade components; however, disruption of the KSR1/CK2 interaction or inhibition of CK2 activity significantly reduces the growth-factor-induced phosphorylation of C-Raf and B-Raf on the activating serine site in the negative-charge regulatory region (N-region). This decrease in Raf N-region phosphorylation further correlates with impaired Raf, MEK, and ERK activation. These findings identify CK2 as a novel component of the KSR1 scaffolding complex that facilitates ERK cascade signaling by functioning as a Raf family N-Region kinase.


Immunolocalization of a putative cuticular collagen protein in several developmental stages of Meloidogyne arenaria, Globodera pallida and G. rostochiensis.
The monoclonal antibody IACR-CCNj.3d has previously been used to isolate a gene (gp-col-8) with strong similarity to cuticular collagen from a mixed stage Globodera pallida cDNA expression library. The antibody has also been shown to label specifically the amphidial canal of pre-parasitic second stage juveniles (J2) of several plant nematode species without any reactivity on the cuticular surface, indicating that this protein is either not present or is inaccessible on the cuticular surface. This paper investigates the cross-reactivity of Mab IACR-CCNj.3d with Meloidogyne arenaria and the localization of the putative collagen protein on the cuticular surface of parasitic stages in planta and on the cuticular surface of juveniles inside eggs. The antigen was shown to be present in all developmental stages of the two species of potato cyst nematodes and M. arenaria. The antibody bound strongly to the amphidial canal and hypodermis of pre-parasitic J2 and adult females. The antigen was present on the cuticular surface of the sausage-shaped J2 in planta and of first stage juveniles (J1) inside the eggs. The presence of collagen on the surface of the cuticle of moulting stages of plant parasitic nematodes has been observed for the first time. It is clear that this protein has a role in the construction of the cuticle of the first stage juveniles and parasitic second stage juveniles, during moulting inside the eggs and in the root tissue, respectively.


Architecture evaluation for the implementation of a regional integrated electronic health record.
The interconnection between different healthcare information systems is not yet a trivial task. Solid communication infrastructures do exist, solid solutions for Health Information Systems (HIS) are installed, but, unfortunately, too many different solutions hinder the integration of HIS at a regional, national or European level.In this paper we propose a solution and an implementation of an Integrated Electronic Health Record that is a composition of two distinct integration models - centralized and distributed. We exploit this solution against a set of predefined users and institutional requirements, at a regional level in two Portuguese regions. As a conclusion, an evaluation of the cost and inherent benefits is made involving the clinical, economical and organizational perspectives.


[Treatment of Urban Runoff Pollutants by a Multilayer Biofiltration System].
In order to control the non-point source pollution from road runoff in Wuxi City effectively, a multilayer biofiltration system was designed to remove a variety of pollutants according to the characteristics of road runoff in Wuxi, and the experimental research was carried out to study the effect on rainwater pollution purification. The results show that the system has a good performance on removing suspended solids (SS), organic pollutant (COD), nitrogen and phosphorus: all types of multilayer biofiltration systems have a high removal rate for SS, which can reach 90%. The system with activated carbon (GAC) has higher removal rates for COD and phosphorus. The system with zeolite (ZFM) has a relatively better removal efficiency for nitrogen. The addition of wood chips in the system can significantly improve the system efficiency for nitrogen removal. Between the two configurations of layered and distributed wood chips, configurations of distributed wood chips reach higher COD, phosphorus and nitrogen pollutants removal efficiencies since they can reduce the release of wood chips dissolution.


NADH oxidation and NAD+ reduction catalysed by tightly coupled inside-out vesicles from Paracoccus denitrificans.
Tightly coupled inside-out vesicles were prepared from Paracoccus denitrificans cells (SPP, sub-Paracoccus particles) and characterized kinetically. The rate of NADH oxidation, catalysed by SPP, increases 6-8 times on addition of gramicidin. The vesicles are capable of catalysing Delta micro H+-dependent reverse electron transfer from quinol to NAD+. The kinetic parameters of the NADH-oxidase and the reverse electron transfer carried out by membrane-bound P. denitrificans complex I were estimated and compared with those of the mitochondrial enzyme. The data demonstrate that catalytic properties of the dinucleotide-binding site of the bacterial and mitochondrial complex I are almost identical, pointing out similar organization of the site in mammals and P. denitrificans. Inhibition of the bacterial complex I by a specific inhibitor of Q reduction, rotenone, is very different from that of the mitochondrial enzyme. The inhibitor is capable of suppressing the NADH oxidation reaction only at micromolar concentrations, while the activity of mitochondrial enzyme is suppressed by nanomolar concentrations of rotenone. In contrast to the mitochondrial enzyme, rotenone, even at concentrations as high as 10 micro m, does not inhibit the reverse, Delta micro H+-dependent NAD+-reductase reaction on SPP.


Variola minor in Braganca Paulista County, 1956. Flow of the epidemic through the schools of the county.
The characteristics of the 10 elementary, teachers, business and high schools operated in the city capital of the Braganca Paulista County, state of São Paulo, Brazil, during the 1956 epidemic of variola minor (alastrim) are presented. Also shown are the numbers of students with variola and of students without variola but with homemates with variola, by grade and school. Of the total 131 cases recorded among students, 128 occurred in the 4 elementary schools. Of the latter cases, 101 occurred among the students of the JG School and the JT School. The distribution of these cases by age, sex, previous immunity status, school grade and clinical severity of the disease (typed according to Dixon's classification) were remarkably similar in these two schools. Only the ratio of students introducing the disease into their households to students having secondary cases in their households suggestively varied, the JT School having more introductory cases. No student with a previous attack of variola showed any clinical manifestation in any school. Only 2 of the total 101 cases from the JG and JT Schools occurred among students with a previous successful vaccination. Moreover, those two cases apparently resulted from within-household contacts rather than from contacts at the school. No student with current variola showed a severe type (Dixon's types 1 to 5). More than half of the cases typed showed the typical, medium-severity type (Dixon's type 6). More than 2/3 of the cases occurred among students aged 6 to 9 years, particularly among those 7- to 9-year old. The number of cases reached a maximum in the first grade and gradually and definitely decreased with increasing grade.


Cost-effectiveness of male circumcision for HIV prevention in a South African setting.
Consistent with observational studies, a randomized controlled intervention trial of adult male circumcision (MC) conducted in the general population in Orange Farm (OF) (Gauteng Province, South Africa) demonstrated a protective effect against HIV acquisition of 60%. The objective of this study is to present the first cost-effectiveness analysis of the use of MC as an intervention to reduce the spread of HIV in sub-Saharan Africa. Cost-effectiveness was modeled for 1,000 MCs done within a general adult male population. Intervention costs included performing MC and treatment of adverse events. HIV prevalence was estimated from published estimates and incidence among susceptible subjects calculated assuming a steady-state epidemic. Effectiveness was defined as the number of HIV infections averted (HIA), which was estimated by dynamically projecting over 20 years the reduction in HIV incidence observed in the OF trial, including secondary transmission to women. Net savings were calculated with adjustment for the averted lifetime duration cost of HIV treatment. Sensitivity analyses examined the effects of input uncertainty and program coverage. All results were discounted to the present at 3% per year. For Gauteng Province, assuming full coverage of the MC intervention, with a 2005 adult male prevalence of 25.6%, 1,000 circumcisions would avert an estimated 308 (80% CI 189-428) infections over 20 years. The cost is 181 dollars (80% CI 117-306 dollars) per HIA, and net savings are 2.4 million dollars (80% CI 1.3 million to 3.6 million dollars). Cost-effectiveness is sensitive to the costs of MC and of averted HIV treatment, the protective effect of MC, and HIV prevalence. With an HIV prevalence of 8.4%, the cost per HIA is 551 dollars (80% CI 344-1,071 dollars) and net savings are 753,000 (80% CI 0.3 million to 1.2 million dollars). Cost-effectiveness improves by less than 10% when MC intervention coverage is 50% of full coverage. In settings in sub-Saharan Africa with high or moderate HIV prevalence among the general population, adult MC is likely to be a cost-effective HIV prevention strategy, even when it has a low coverage. MC generates large net savings after adjustment for averted HIV medical costs.


[Basal blood level of serotonin in diabetes mellitus patients].
Blood serotonin was determined in 184 patients with diabetes mellitus by a biological method. Its average value in diabetics was significantly lower than that of the control healthy subjects. The changes established show a light dependence on sex and age of the patients, duration and type of the disease, blood sugar level and the kind of drug treatment. They are better manifested in the presence of retinopathy versus in its absence, as well as in the presence of proliferative versus non-proliferative one. With the compensation of the diabetes, a tendency to partial normalization of serotonin blood level was observed. The probable causes of serotonin changes established are discussed.


Laboratory data supporting the clinical trial of anti-rabies serum in persons bitten by a rabid wolf.
Five individuals severely exposed to rabies by wolf bite and treated with a course of phenolized vaccine alone showed no demonstrable antibodies in their sera until the nineteenth day following the start of treatment. Three of these five individuals died of rabies.On the other hand, twelve individuals similarly exposed, who received antirabies serum plus a course of phenolized vaccine, had demonstrable antibodies early in and throughout the period of observation. One individual who received one dose of serum plus a course of vaccine died of rabies.In view of these results, it is apparent that antibody demonstrable early in and throughout the treatment period, and obtained by the combined use of serum and vaccine, is more effective in preventing rabies after severe exposure than is a course of vaccine alone.


US features of normal parathyroid glands: a comparison with metastatic lymph nodes in thyroid cancer.
This study aimed to determine the ultrasound (US) features of normal parathyroid glands (PTGs) and to evaluate whether normal PTGs can be differentiated from metastatic lymph nodes (LNs) in thyroid cancer. This retrospective study included 10 normal PTGs and 95 metastatic LNs from thyroid cancer showing suspicious US features. The echogenicity, echotexture, echogenic foci (calcifications), cystic change, abnormal vascularity, size, shape, and location were retrospectively assessed and compared between normal PTGs and metastatic LNs. The echogenicity of normal PTGs was significantly different from that of metastatic LNs (P<0.001). Normal PTGs exhibited marked hyperechogenicity (100%), homogeneous echotexture (80%), focal intraglandular hypoechogenicity (20%), ovoid shape (90%), and focal cystic change in one case (10%). The echogenicity of metastatic LNs was markedly hyperechoic (0%), moderately hyperechoic (15.8%), mildly hyperechoic (53.7%), and hypoechoic (28.4%). The size and long axis/short axis ratios of normal PTGs were significantly smaller and larger than those of metastatic LNs (P<0.01 and P=0.022, respectively). Marked hyperechogenicity was found only in normal PTGs, and small, ovoid, markedly hyperechoic structures in the paramedian central neck characterized normal PTGs. Normal PTGs may be differentiated from metastatic LNs in thyroid cancer.


Self-reported visual dysfunction in multiple sclerosis: new data from the VFQ-25 and development of an MS-specific vision questionnaire.
To examine vision-specific health-related quality of life in a cohort of patients with multiple sclerosis (MS) using the 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25), and to identify content areas for a brief MS-specific vision questionnaire. Cross-sectional survey. The VFQ-25 and a modified version of the Optic Neuritis Treatment Trial (ONTT) Patient Questionnaire were administered by in-person interview to 80 patients at the University of Pennsylvania MS Center. Binocular visual acuities were obtained following a standard protocol using retroilluminated Early Treatment Diabetic Retinopathy Study charts. Despite a median binocular visual acuity of 20/16 (20/12.5-20/250), VFQ-25 subscale scores in the MS cohort were significantly lower (worse) compared with those of a published reference group of eye disease-free patients (P =.0001-0.009, two-tailed t tests). Rank-correlations of VFQ-25 composite (overall) scores with visual acuity were modest, but significant (r(s) = 0.33, P =.003), supporting construct validity for VFQ-25 scores in MS populations. Seven additional aspects of self-reported visual dysfunction in MS were also identified. Patients with MS have a high degree of self-reported visual dysfunction that is not entirely captured by visual acuity. The VFQ-25 is an effective measure of self-reported visual loss in MS. A brief MS-specific vision questionnaire may provide additional useful information when administered concurrently with the VFQ-25 in future investigations of MS and other neuroophthalmologic disorders.


Comparison of dobutamine and levosimendan for treatment of sepsis-induced cardiac dysfunction: A protocol for systematic review and meta-analysis.
Levosimendan and dobutamine are extensively used to treat sepsis-induced cardiomyopathy. Previous studies on whether levosimendan is superior to dobutamine are still controversial. We performed a protocol for systematic review and metaanalysis to compare the efficacy and safety of levosimendan versus dobutamine for the treatment of sepsis-induced cardiomyopathy. This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol statement. We will search the following databases: PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Weipu Journal Database, and Chinese Biomedical Literature Database. The search time will be set from database establishment to February 2022. After literature screening, 2 reviewers will extract data from the respects of general information, methodology, and results. Risk of bias is assessed using the Cochrane Risk of Bias Tool for randomized controlled trials. We will apply RevMan 5.4 software for statistical analysis. The results will be submitted to a peer-reviewed journal once completed. Septic patients with myocardial dysfunction may partly benefit from levosimendan than dobutamine, mainly embodied in cardiac function improvement.


Use of hypnosis in patients receiving hemodialysis for end stage renal disease.
Dialysis patients experience considerable psychologic stress, but practical issues impede delivery of psychiatric care. The authors describe five cases in which the use of hypnosis for symptom reduction provided the basis for beneficial psychiatric intervention.


Analyzing the teaching style of nursing faculty. Does it promote a student-centered or teacher-centered learning environment?
The purposes of this study were to a) describe the predominant teaching style of a group of nursing faculty members, either as teacher centered or student centered, and b) to compare teaching style to the instructional methods the faculty members used in the courses they taught and to their stated philosophies of teaching/learning. Findings indicate that the participants were more teacher centered than student centered; their written philosophies supported the teacher-centered approach. However, evidence that faculty used student-centered language, often in a teacher-centered context, indicates that participants in the study may recognize the need for a student-centered environment but may have difficulty with implementation. Recommendations for faculty members and administrators are offered.


Atopic dermatitis: skin-directed management.
Atopic dermatitis is a common inflammatory skin condition characterized by relapsing eczematous lesions in a typical distribution. It can be frustrating for pediatric patients, parents, and health care providers alike. The pediatrician will treat the majority of children with atopic dermatitis as many patients will not have access to a pediatric medical subspecialist, such as a pediatric dermatologist or pediatric allergist. This report provides up-to-date information regarding the disease and its impact, pathogenesis, treatment options, and potential complications. The goal of this report is to assist pediatricians with accurate and useful information that will improve the care of patients with atopic dermatitis.


COLD Fusion: Calibrated and Ordinal Latent Distribution Fusion for Uncertainty-Aware Multimodal Emotion Recognition.
Automatically recognising apparent emotions from face and voice is hard, in part because of various sources of uncertainty, including in the input data and the labels used in a machine learning framework. This paper introduces an uncertainty-aware multimodal fusion approach that quantifies modality-wise aleatoric or data uncertainty towards emotion prediction. We propose a novel fusion framework, in which latent distributions over unimodal temporal context are learned by constraining their variance. These variance constraints, Calibration and Ordinal Ranking, are designed such that the variance estimated for a modality can represent how informative the temporal context of that modality is w.r.t. emotion recognition. When well-calibrated, modality-wise uncertainty scores indicate how much their corresponding predictions are likely to differ from the ground truth labels. Well-ranked uncertainty scores allow the ordinal ranking of different frames across different modalities. To jointly impose both these constraints, we propose a softmax distributional matching loss. Our evaluation on AVEC 2019 CES, CMU-MOSEI, and IEMOCAP datasets shows that the proposed multimodal fusion method not only improves the generalisation performance of emotion recognition models and their predictive uncertainty estimates, but also makes the models robust to novel noise patterns encountered at test time.


Deer meat as the source for a sporadic case of Escherichia coli O157:H7 infection, Connecticut.
We report a case of Escherichia coli O157:H7, which was acquired by eating wild White-Tailed deer (Odocoileus virginianus). DNA fingerprint analysis verified venison as the source of infection. This pediatric case emphasizes the need for dissemination of information to hunters regarding the safe handling and processing of venison.


The brain-stem auditory-evoked response in the big brown bat (Eptesicus fuscus) to clicks and frequency-modulated sweeps.
Three experiments were performed to evaluate the effects of stimulus level on the brain-stem auditory-evoked response (BAER) in the big brown bat (Eptesicus fuscus), a species that uses frequency-modulated (FM) sonar sounds for echolocation. In experiment 1, the effects of click level on the BAER were investigated. Clicks were presented at levels of 30 to 90 dB pSPL in 10-dB steps. Each animal responded reliably to clicks at levels of 50 dB pSPL and above, showing a BAER containing four peaks in the first 3-4 ms from click onset (waves i-iv). With increasing click level, BAER peak amplitude increased and peak latency decreased. A decrease in the i-iv interval also occurred with increasing click level. In experiment 2, stimuli were 1-ms linear FM sweeps, decreasing in frequency from 100 to 20 kHz. Stimulus levels ranged from 20 to 90 dB pSPL. BAERs to FM sweeps were observed in all animals for levels of 40 dB pSPL and above. These responses were similar to the click-evoked BAER in waveform morphology, with the notable exception of an additional peak observed at the higher levels of FM sweeps. This peak (wave ia) occurred prior to the first wave seen at lower levels (wave ib). As the level of the FM sweep increased, there was a decrease in peak latency and an increase in peak amplitude. Similarity in the magnitude and behavior of the i-iv and ib-iv intervals suggests that wave ib to FM sweeps is the homolog of the wave i response to click stimuli. Experiment 3 tested the hypothesis that wave ia represented activity emanating from more basal cochlear regions than wave ib. FM sweeps (100-20 kHz) were presented at 90 dB pSPL, and broadband noise was raised in level until the BAER was eliminated. This "masked threshold" occurred at 85 dB SPL of noise. At masked threshold, the broadband noise was steeply high-pass filtered at five cutoff frequencies ranging from 20 to 80 kHz. Generally, wave ia was eliminated for masker cutoff frequencies of 56.6 kHz and below, while wave ib was typically observed for masker cutoffs down to 28.3 kHz. The results of these three experiments are compared and contrasted with data from other mammalian BAER studies.


Gray zone of hepatitis B virus infection.
A substantial proportion of patients with chronic hepatitis B (CHB) do not fall into any of the defined phases and are considered to be in the "gray zone" or "indeterminate phase." Most of the current clinical practice guidelines have no recommendations for antiviral treatment for them. However, the gray zone CHB patients with significant hepatitis B virus levels (>2000 IU/mL) and persistently normal alanine aminotransferase (ALT) levels have a significantly high risk of hepatic inflammation, fibrosis, and hepatocellular carcinoma. The molecular, clinical, and economic data that we have reviewed collectively in this article provide support for simplification of treatment initiation strategies that incorporate broader treatment of adult patients with CHB in the gray zone (hepatitis B virus [HBV] DNA ≥2000 IU/mL), regardless of ALT levels.


Usefulness of collagen gel droplet embedded culture drug sensitivity testing in ovarian cancer.
Due to the emergence of new anticancer agents for the treatment of ovarian cancer, methods to determine which agents will be most effective in individual patients are required. In order to investigate the potential for tailor-made chemotherapy, the drug sensitivities of various ovarian cancers were examined using collagen gel droplet embedded culture drug sensitivity testing (CD-DST), and the results were correlated with clinical outcomes. Sensitivities to paclitaxel, cisplatin, doxorubicin, etoposide, and SN-38, which is an active metabolite of irinotecan, were examined. Eight out of 22 samples failed to grow colonies and thus, their cell sensitivities could not be determined. Out of the 14 cases from which CD-DST results were obtained, seven patients then received chemotherapy aimed at inducing remission, while four received adjuvant, and three did not receive any chemotherapy. Three of the four tumors subsequently treated with adjuvant chemotherapy showed sensitivity to TXL and CDDP on CD-DST analysis, while one did not. None of these patients experienced recurrent disease from 24 to 36 months. Five of the seven tumors subsequently treated with chemotherapy aimed at inducing remission showed sensitivity to the relevant anticancer agents upon CD-DST analysis, while two did not. Among the five cases that showed tumor cell sensitivity, three experienced complete responses, one achieved a partial response and one had progressive disease. For the remaining two cases that demonstrated tumor cell resistance, one had stable disease and one had progressive disease following chemotherapy. Thus, six out of the seven cases (85.7%) that received chemotherapy aimed at inducing remission had clinical outcomes in keeping with the results of CD-DST. In conclusion, CD-DST results reflect clinical outcomes and may be a useful means by which to select drugs to which ovarian cancer cells are chemosensitive.


Experimental brain inflammation and neurodegeneration as model of Alzheimer's disease: protective effects of selective COX-2 inhibitors.
Epidemiological studies indicate that long-term treatment with non-steroidal anti-inflammatory drugs reduces the risk of Alzheimer Disease and may delay its onset or slow its progression. Neuroinflammation occurs in vulnerable regions of the Alzheimer's disease (AD) brain where highly insoluble beta-amyloid (Abeta) peptide deposits and neurofibrillary tangles, as well as damaged neurons and neurites, provide stimuli for inflammation. To elucidate the complex role of inflammation in neurodegenerative processes and the efficacy of selective COX-2 inhibitors in AD, we examined whether the attenuation of brain inflammatory reaction by selective COX-2 inhibitors may protect neurons against neurodegeneration. The data reported in this review show that in in vivo models of brain inflammation and neurodegeneration, the administration of selective COX-2 inhibitors prevent not only the inflammatory reaction, but also the cholinergic hypofunction. Our data may help elucidate the epidemiological findings indicating that anti-inflammatory agents, in particular NSAIDs, reduce the risk of developing AD and may slow its progression.


Local Public Health Surveillance of Heroin-Related Morbidity and Mortality, Orange County, Florida, 2010-2014.
Heroin-related deaths have increased substantially in the past 10 years in the United States, particularly in Florida. Our objectives were to measure heroin-related morbidity and mortality rates in Orange County, Florida, and to assess trends in those rates during 2010-2014. We used 3 heroin surveillance methods, based on data from the Florida Medical Examiner, the Florida Agency for Health Care Administration (AHCA), and the Electronic Surveillance System for the Early Notification of Community-Based Epidemics-Florida (ESSENCE-FL). We conducted descriptive and geographic spatial analyses of all 3 data sets, determined heroin-related mortality and morbidity (emergency department [ED] visit) rates, and compared the timeliness of data availability from the 3 data sources. Heroin-related deaths in Orange County increased by 590%, from 10 in 2010 to 69 in 2014. Heroin-related ED visits during the same period increased 12-fold (from 13 to 154) and 6-fold (from 49 to 307) when based on AHCA and ESSENCE-FL data, respectively. ESSENCE-FL identified 140% more heroin-related visits than did AHCA. Spatial analysis found geographic clustering of heroin-related morbidity and mortality. Hospitals facing the greatest burden of heroin-related ED visits were close to communities with the highest crude heroin-related ED visit rates. Of the 3 data sources, ESSENCE-FL provided the timeliest data availability. These 3 data sources can be considered acceptable surveillance systems for monitoring heroin-related events in Orange County. The timely availability of data from ESSENCE-FL makes it the most useful source for obtaining near-real-time data about the heroin epidemic, potentially leading to improved identification of populations most in need of interventions to reduce morbidity and mortality.


Echocardiographic demonstration of Escherichia coli endocarditis restricted to the pulmonary valve.
A 25 year old man with no history of heart disease presented with sweats and rigors. Echocardiography showed a large vegetation on the pulmonary valve and blood cultures grew Escherichia coli. Because of recurrent pulmonary emboli a large vegetation on the anterior leaflet of the pulmonary valve was excised. He recovered after a full course of antibiotics.


Kinetic control of the supramolecular chirality of porphyrin J-aggregates.
The aggregation of achiral sulfonatophenyl- and phenyl-meso-substituted diprotonated porphyrins to chiral J-aggregates is a hierarchical noncovalent polymerization process preceded by a critical nucleation stage. This allows significant enantiomeric excesses by the formation of a few primary nuclei and the control of their growth by the effect that flows (imperfect mixing) have on the secondary nucleation of the J-aggregate particles. In addition, the results strongly suggest that when only one species of aggregate predominates, the CD signals of the three excitonic bands in the visible region (around 420, 490, and 700 nm) show the same sign. Thus, differences on their relative sign would be due to the presence of different species.


Dual Role of Triptolide in Interrupting the NLRP3 Inflammasome Pathway to Attenuate Cardiac Fibrosis.
In a previous paper, we reported that triptolide (TP), a commonly used immunomodulator, could attenuate cardiac hypertrophy. This present study aimed to further explore the inhibition of cardiac fibrosis by TP and the possible mechanism from the perspective of the NOD-like receptor protein 3 (NLRP3) inflammasome. Hematoxylin-eosin and Masson's staining, immunohistochemistry, and immunofluorescence were performed to observe cardiac fibrotic changes in mice and mouse cardiac fibroblasts (CFs). The Western blot, colocalization, and immunoprecipitation were applied to detect protein expression and interactions. Results suggested that TP dose-dependently inhibited cardiac fibrosis induced by isoproterenol and collagen production of CFs induced by angiotensin II. TP exhibited an antifibrotic effect via inhibiting activation of the NLRP3 inflammasome, which sequentially decreased IL-1β maturation, myeloid differentiation factor 88 (MyD88)-related phosphorylation of c-Jun N-terminal kinase (JNK), extracellular regulated protein kinase 1/2 (ERK1/2), and TGF-β1/Smad signaling, and ultimately resulted in less collagen production. Moreover, TP showed no antifibrotic effect in Nlrp3-knockout CFs. Notably, TP inhibited the expression of NLRP3 and apoptosis-associated speck-like proteins containing a caspase recruitment domain (ASC) as well as inflammasome assembly, by interrupting the NLRP3-ASC interaction to inhibit inflammasome activation. Finally, TP indeed inhibited the NLRP3-TGFβ1-Smad pathway in vivo. Conclusively, TP was found to play a dual role in interrupting the activation of the NLRP3 inflammasome to attenuate cardiac fibrosis.


The Importance of Spin State in Chiral Supramolecular Electronics.
The field of spintronics explores how magnetic fields can influence the properties of organic and inorganic materials by controlling their electron's spins. In this sense, organic materials are very attractive since they have small spin-orbit coupling, allowing long-range spin-coherence over times and distances longer than in conventional metals or semiconductors. Usually, the small spin-orbit coupling means that organic materials cannot be used for spin injection, requiring ferromagnetic electrodes. However, chiral molecules have been demonstrated to behave as spin filters upon light illumination in the phenomenon described as chirality-induced spin selectivity (CISS) effect. This means that electrons of certain spin can go through chiral assemblies of molecules preferentially in one direction depending on their handedness. This is possible because the lack of inversion symmetry in chiral molecules couples with the electron's spin and its linear momentum so the molecules transmit the one preferred spin. In this respect, chiral semiconductors have great potential in the field of organic electronics since when charge carriers are created, a preferred spin could be transmitted through a determined handedness structure. The exploration of the CISS effect in chiral supramolecular semiconductors could add greatly to the efforts made by the organic electronics community since charge recombination could be diminished and charge transport improved when the spins are preferentially guided in one specific direction. This review outlines the advances in supramolecular chiral semiconductors regarding their spin state and its influence on the final electronic properties.


Congenital absence of the long head of biceps tendon & its clinical implications: a systematic review of the literature.
Multiple reports of congenitally absent long head of biceps tendon (LHBT) have been reported in the literature. However, there is no consensus on the clinical implications of this relatively rare entity. To systematically review and analyze all studies which have reported absence of LHBT. PubMed and EMBASE databases were searched. Also, a secondary search was performed by pearling the bibliography of all the full-text articles obtained. Pre defined inclusion criteria was used for abstract screening by two independent observers. Twenty three studies met our inclusion criteria, were included for the final analysis and the data was pooled. The cases were further sub-grouped according to the classification of Dierickx et al. Till date, 35 cases of absent LHBT have been reported. Males and females were equally affected. Eight of these were bilateral and only four cases had other associated congenital anomalies. Majority of the patients presented with shoulder pain (85.7%) while 37.1% had shoulder instability (mainly anterior instability). The ABS type was the most common variant reported. The finding was missed in 60% of the cases on the initial MRI only to be detected later on shoulder arthroscopy. Congenitally absent LHBT may not be as rare as was previously thought to be. Due to the heterogeneity and the low level of evidence of the data available, it is hard to conclude if a congenitally absent LHBT is a cause of shoulder pain/impingement or instability on its own. IV.


Prevalence of antibiotic resistance genes and bacterial pathogens in long-term manured greenhouse soils as revealed by metagenomic survey.
Antibiotic resistance genes (ARGs), human pathogenic bacteria (HPB), and HPB carrying ARGs pose a high risk to soil ecology and public health. Here, we used a metagenomic approach to investigate their diversity and abundance in chicken manures and greenhouse soils collected from Guli, Pulangke, and Hushu vegetable bases with different greenhouse planting years in Nanjing, Eastern China. There was a positive correlation between the levels of antibiotics, ARGs, HPB, and HPB carrying ARGs in manures and greenhouse soils. In total, 156.2–5001.4 μg/kg of antibiotic residues, 22 classes of ARGs, 32 HPB species, and 46 species of HPB carrying ARGs were found. The highest relative abundance was tetracycline resistance genes (manures) and multidrug resistance genes (greenhouse soils). The dominant HPB and HPB carrying ARGs in the manures were Bacillus anthracis, Bordetella pertussis, and B. anthracis (sulfonamide resistance gene, sul1), respectively. The corresponding findings in greenhouse soils were Mycobacterium tuberculosis and M. ulcerans, M. tuberculosis (macrolide-lincosamide-streptogramin resistance protein, MLSRP), and B. anthracis (sul1), respectively. Our findings confirmed high levels of antibiotics, ARGs, HPB, and HPB carrying ARGs in the manured greenhouse soils compared with those in the field soils, and their relative abundance increased with the extension of greenhouse planting years.


A gas microstrip detector for XAS studies in the photon energy region 300-1500 eV.
The ability to perform X-ray absorption spectroscopy (XAS) in the 300-1500 eV energy range allows measurements to be made on transition metal compounds. This paper describes a detector and the technique used to perform fluorescent measurements on such materials. A variety of test sample results are shown to illustrate the low energy and energy-resolving capabilities of the detector (based on gas microstrip technology). Two possible applications are also demonstrated. The first shows how the detector can be used to gather X-ray absorption spectra for the L edges of transition metals and K edges of light elements (C, O and N). The other shows how the magnetic immunity of the detector can be exploited to study the magnetic properties of materials.


Carotid and lower extremity arterial disease in patients with renal artery atherosclerosis.
Atherosclerotic lesions of the carotid and lower extremity arteries may be associated with renal artery stenosis and influence the management of patients with renal artery disease. To document the prevalence and clinical features of carotid and lower extremity arterial disease in patients with renal artery atherosclerosis. An analysis of baseline data on 149 patients enrolled in a prospective natural history study of atherosclerotic renal artery stenosis. Patients with at least 1 abnormal renal artery by duplex scanning were eligible. Carotid artery disease was evaluated by duplex scanning, and ankle/brachial indices were used to assess the lower extremity arteries. Disease at each of the 3 arterial sites was classified as mild, moderate, or severe based on the extent of involvement on both sides. Serum urea nitrogen, creatinine, and lipid levels were also measured. Severe renal, carotid, or lower extremity arterial disease was present in 44%, 19%, and 21% of the patients, respectively. There was a trend for patients with increasing degrees of renal artery disease to have increasing degrees of carotid and lower extremity arterial disease. The prevalence of severe carotid artery disease increased from 7% in the mild renal artery group to 28% in the severe renal artery group. Clinical factors that were most predictive of severe disease were elevated apolipoprotein B levels for the renal arteries, high serum urea nitrogen or creatinine levels for the carotid arteries, and smoking for the lower extremity arteries. There was a strong association between severe renal artery atherosclerosis and severe carotid artery disease. Patients with renal artery disease also had a high prevalence of lower extremity arterial disease. In this patient population, screening for lower extremity arterial disease can be reserved for those with signs or symptoms of peripheral ischemia. Noninvasive carotid screening is justified in patients with renal artery disease to detect asymptomatic lesions that require either immediate surgical treatment or serial follow-up for disease progression.


Lupus anticoagulant and anticardiolipin antibodies in polytransfused beta thalassemia major.
The currently used therapeutic strategies in beta thalassemia have prolonged the survival for many patients; this longer survival has been accompanied by the development of a number of unexpected complications, these include hemostatic derangements. The presence of anti-phospholipid antibodies (APA) (lupus anticoagulant, LA and anti-cardiolipid antibody, ACA) has recently been reported in polytransfused patients of beta thalassemia. In this study 50 patients with beta thalassemia major (beta-TM) who had received at least 20 transfusions were evaluated for presence of antiphospholipid antibodies and correlated with a number of clinical and hemostatic parameters. About 32% cases had developed a minor bleeding tendency and one also showed ecchymotic patch. None of the patients had thromboembolic episodes. LA was seen in 16% of cases. The mean age and number of transfusions were higher in LA positive patients as compared to LA negative patients however the results were not statistically significant. IgM ACA were detected in 6% of patients but no statistically significant correlation was found with age, number of transfusions, platelet count and coagulation parameters. IgG ACA were detected in 30% of cases and showed a significant correlation with number of blood transfusions (p = 0.016) and age (p = 0.031). Anti HCV antibodies were detected in 30% of patients out of which 1 had IgM ACA and 10 had IgG ACA. The latter showed a significant correlation with HCV infection. An increased incidence of LA and IgG ACA is found in polytransfused patients with beta-TM when compared to the normal healthy population but their clinical significance is yet not clearly understood.


Pediatric red ear syndrome: A case report of an erythromelalgia type and review of the literature.
Red ear syndrome has been reported in the literature to have similarities to erythromelalgia with auricular involvement; however, the distinction between the two is controversial. Red ear syndrome has previously been classified as idiopathic (primary) or secondary, with headaches being the most common association in the idiopathic or primary form. We present a case of pediatric red ear syndrome with hand and foot involvement that we believe represents auricular erythromelalgia. In this report, we propose a classification system to unify the diagnoses of red ear syndrome and erythromelalgia and review the literature on pediatric cases of red ear syndrome.


In Vitro Characterization of Human Cytomegalovirus-Targeting Therapeutic Monoclonal Antibodies LJP538 and LJP539.
Human cytomegalovirus (HCMV) infection is usually benign in healthy individuals but can cause life-threatening disease in those with compromised immune systems. Approved drugs available to treat HCMV disease, including ganciclovir, cidofovir, and foscarnet, have significant toxicities that limit their use in certain patient populations. LJP538 and LJP539 are human monoclonal antibodies that are being evaluated as immunoglobulin therapeutics. The antibodies target glycoproteins gB and the gH/gL/UL128/UL130/UL131a pentameric complex, respectively. Here we present an in vitro characterization of these antibodies. We show that LJP538 and LJP539 are more potent than a marketed immunoglobulin at inhibiting HCMV infection of various cell lines relevant to pathogenesis. We find that LJP538 and LJP539 are active against a panel of clinical isolates in vitro and demonstrate minor-to-moderate synergy in combination. Passage of HCMV in the presence of LJP538 or LJP539 alone resulted in resistance-associated mutations that mapped to the target genes. However, no loss of susceptibility to the combination of antibodies was observed for >400 days in culture. Finally, the binding regions of LJP538 and LJP539 are conserved among clinical isolates. Taken together, these data support the use of LJP538 and LJP539 in combination for clinical trials in HCMV patients.


Microglial and Astrocytic Function in Physiological and Pathological Conditions: Estrogenic Modulation.
There are sexual differences in the onset, prevalence, and outcome of numerous neurological diseases. Thus, in Alzheimer's disease, multiple sclerosis, and major depression disorder, the incidence in women is higher than in men. In contrast, men are more likely to present other pathologies, such as amyotrophic lateral sclerosis, Parkinson's disease, and autism spectrum. Although the neurological contribution to these diseases has classically always been studied, the truth is that neurons are not the only cells to be affected, and there are other cells, such as glial cells, that are also involved and could be key to understanding the development of these pathologies. Sexual differences exist not only in pathology but also in physiological processes, which shows how cells are differentially regulated in males and females. One of the reasons these sexual differences may occur could be due to the different action of sex hormones. Many studies have shown an increase in aromatase levels in the brain, which could indicate the main role of estrogens in modulating proinflammatory processes. This review will highlight data about sex differences in glial physiology and how estrogenic compounds, such as estradiol and tibolone, could be used as treatment in neurological diseases due to their anti-inflammatory effects and the ability to modulate glial cell functions.


Chemical communication between vagal afferent somata in nodose Ganglia of the rat and the Guinea pig in vitro.
The cell bodies of spinal afferents, dorsal root ganglion neurons, are depolarized several millivolts, and their probability of spiking increased when axons of neighboring somata in the same ganglion are electrically stimulated repetitively. This form of neural communication has been designated cross-depolarization (CD) and cross-excitation (CE). The existence of CD and CE between somata of vagal afferents (nodose ganglion neurons, NGNs) of rats and guinea pigs was investigated by electrically stimulating the vagus nerve while recording the electrical activity of NGNs in intact nodose ganglia with sharp intracellular microelectrodes. CD and CE in NGNs were manifested by a membrane depolarization (approximately 4 mV), the presence of spontaneous action potentials, and a decreased spike threshold. CD was dependent on the frequency and intensity of vagal nerve stimulation. Two distinct types of CD were observed: 1) in NGNs with large input resistances (R(in)), CD was dependent on [Ca2+]o, associated with increased membrane conductance, and had an extrapolated reversal potential (E(rev)) value of about -25 mV; and 2) in NGNs with low R(in), CD was independent of [Ca2+]o, not accompanied by a membrane conductance change, or a measurable E(rev) value. These data reveal the existence of a chemical communication pathway between vagal afferent somata and suggest the possibility that communication between different visceral organs may occur at the level of the primary vagal afferent neuron.


Effect of ionic liquids in carbon nanotube bundles on CO2, H2S, and N2 separation from CH4: A computational study.
Carbon nanotube (CNT) bundles are being explored as a support structure for four ionic liquids (ILs) in gas separation. Grand canonical Monte Carlo simulations were performed to investigate the CO2/CH4, H2S/CH4, and N2/CH4 separation performance in CNT bundles and CNT-supported ILs (CNT-ILs) as a function of pressure and IL loading. The results show that by adding ILs to the CNT bundles, the gas separation performance can be significantly increased. Increasing the number of IL molecules in the composites increases the separation performance. Such a phenomenon is more evident for the CO2/CH4 mixture in comparison to H2S/CH4 and N2/CH4. Calculations of isosteric heat of adsorption and selectivities in gas mixtures as a function of pressure show promising gas separation performance for CNT-ILs. Due to the excellent mechanical properties of CNTs, it has been shown that this structure may be used as a strong mechanical support for structures containing ILs with excellent CO2/CH4 separation performance.


Primary central nervous system vasculitis and headache: Ten themes.
The primary central nervous system (CNS) vasculitides refers to clinicopathologic disorders that share the histopathology of inflammation of cerebral or spinal blood vessels. Unrecognized and therefore untreated, vasculitis of the CNS results in irreversible injury and disability making these disorders of paramount importance to clinicians. Headache is an important clue to vasculitic involvement of CNS vessels. CNS vasculitis can be primary, in which only intracranial or spinal vessels are involved in the inflammatory process, or secondary to another known disorder with overlapping systemic involvement. The suspicion of vasculitis based on the history, clinical examination, and laboratory studies warrants prompt evaluation and treatment to prevent cerebral ischemia or infarction. Primary CNS vasculitides can be diagnosed with certainty after intensive evaluation that includes tissue confirmation whenever possible. As in its systemic counterparts, clinicians must choose from among the available immune modulating, suppressive, and targeted immunotherapies to induce and maintain remission status and prevent relapse, tempered by anticipated medication adverse effects.


[Structure and seasonal aspects of the bat gallbladder].
The gallbladder of the insectivorous hibernating bats (Pipistrellus pipistrellus et Rhinolophus ferrumequinum) in fullness, shows a fundus, a corpus and a neck. Its wall is formed by three layers: mucous membrane, with simple columnar epithelium on a thin basal lamina, beneath which is a "lamina propria" of connective tissue with blood and lymphatic vessels; lamina muscularis, constituted by three of four parallel bundles of smooth muscle cells, arranged in circular pattern; serous membrane of loose connective tissue, with precollecting lymphatic vessels and covered by mesothelial cells. By SEM the luminal surface of mucous membrane shows more or less prominent folds delimiting irregular areas with hexa-pentagonal outlines of the apical region of epithelial cells. This latter present a convex dome aspect with numerous microvilli, not changed significantly, during the different year periods. In summer and autumn the epithelial cells are characterized by developed organelles in supranuclear cytoplasm. During the prehibernating period, chiefly the cytoplasm shows multivesicular and heterogeneous dense bodies. In summer, autumn and initial hibernating period, epithelial cell cytoplasm presents microvilli with prominent "antennulae microvilares", numerous light micropinocytosis vesicles, little rough vesicles in apical portion. The mitochondria, grouping in supranuclear and basal cytoplasm, in lethargy, are characterized by small matrix osmiophilic granules. The epithelial cells are held together near the apical surface by tight and gap junctions, and some rare desmosomes only in Rhinolophus f.e. The cell membranes are deep pleated or interdigitate with wide intercellular spaces during the prehibernating period and experimental arousing, while in lethargy and summer months these present linear outline with scanty invaginations. The Authors compared these morphological aspects of bat gallbladder with other micromammalia's one, underline particularly the functional role of dense bodies, wide intercellular spaces and apical micropinocytosis vesicles. The different seasonal ultrastructural characteristics of epithelial cells are considered in close relation to an absorbing function connecting with balance of different metabolisms.


A rapid method for determination of acetylation phenotype using dapsone.
A rapid, simple one-stage protein precipitation method for the estimation of plasma dapsone (DDS) and monoacetyldapsone (MADDS) concentration by high-pressure liquid chromatography (h.p.l.c.) is described. Its performance in the assignment of acetylator phenotype was compared with a reference h.p.l.c. method utilising an extraction procedure and internal standard. The rapid h.p.l.c. technique combined with measurement of the plasma MADDS/DDS ratio is, in our opinion, the method of choice for the determination of the acetylator phenotype in population studies.


The eosinophilic and amyloid-like materials in adenomatoid odontogenic tumor.
This paper is concerned with the relationship between eosinophilic material (EM) and amyloid-like material and adenomatoid odontogenic tumors. In duct-like structures between opposing rows of tall columnar cells, EM did not stain for amyloid. Under electron microscopy, EM was composed of fibrillar and granular materials, and the fibrillar material was not amyloid. Two different kinds of EM were found in solid cell masses. Lesions from cases 2, 3, 4 and part of case 1 contained small droplet-shaped EM and these EM did not stain for amyloid. Case 1 also contained EM that stained positively for amyloid. The structure of amyloid positive EM resembled developing enamel of human tooth germs. This material was tubular and finely granular. The tubular material resembled enamel matrix fibers rather then amyloid and the fine granular material was stippled. The cells surrounding EM appeared similar to ameloblasts between secretory and maturation stages.


[The expression of prostacyclin in lungs from patients with chronic obstructive pulmonary disease].
to investigate the expression of prostacyclin in lungs from patients with chronic obstructive pulmonary disease (COPD). the lung tissues were obtained from 12 patients with COPD and 10 patients without COPD. The apoptosis of pulmonary vascular endothelial cells was analyzed quantitatively using TdT-mediated dUTP nick end labeling (TUNEL). The expression of PGI2-S protein was assessed by immunohistochemistry of paraffin-embedded tissues. 6-keto Prostaglandin F1a, the stable metabolite of PGI2, was measured by enzyme-linked immunosorbent assay in whole-lung tissue extracts. The data distributed normally were expressed as x(-) +/- s, and the independent-samples t test was used for comparison of means. the apoptotic index (AI) of endothelial cells of medium and small-sized vessels in patients with COPD group [(12.9 +/- 2.0)%, (11.4 +/- 1.4)%] were significantly higher than that of patients without COPD [(6.1 +/- 1.2)%, (5.9 +/- 0.4)%]. In patients without COPD, PGI2-S protein expression in medium vessels and small-sized vessels was (95.4 +/- 2.1)% and (82.3 +/- 7.4)% respectively, and the value was (95.5 +/- 2.2)% in airway epithelial cells. In patients with COPD, PGI2-S expression in medium vessels and small-sized vessels decreased remarkably [(55.2 +/- 9.8)% and (42.3 +/- 5.1)% respectively], and exhibited a marked reduction in airway epithelial cells (31.8 +/- 5.2)%. The level of 6-keto Prostaglandin F1a was significantly lower in patients with COPD (2.6 +/- 0.4)microg/L compared with patients without COPD (16.2 +/- 2.8)microg/L. abnormal apoptosis exists in pulmonary vascular endothelial cells in patients with COPD. In patients with COPD, the expression of PGI2-S and the level of 6-keto Prostaglandin F1a in lung tissues were decreased. The results suggest that abnormal apoptosis, reduction of PGI2-S expression and PGI2 may be important histological markers for pulmonary endothelial cell dysfunction in COPD and may be involved in the pathogenesis of the disease.


Labeling 3' Termini of Double-Stranded DNA Using the Klenow Fragment of E. coli DNA Polymerase I.
The Klenow fragment, which retains the template-dependent deoxynucleotide polymerizing activity and the 3' → 5' exonuclease of the holo-enzyme but lacks its powerful 5' → 3' exonuclease activity, is used to fill recessed 3' termini of dsDNA. In this protocol, fragments suitable as templates for the end-filling reaction are produced by digestion of DNA with an appropriate restriction enzyme. The Klenow enzyme is then used to catalyze the attachment of dNTPs to the recessed 3'-hydroxyl groups.


Epidermal growth factor administered in the periphery influences excitatory synaptic inputs onto midbrain dopaminergic neurons in postnatal mice.
Epidermal growth factor (EGF) has a neurotrophic activity on developing midbrain dopaminergic neurons. We investigated developmental effects of peripheral EGF administration on dopaminergic neurons in midbrain slice preparations containing ventral tegmental area (VTA). Subcutaneous EGF administration to mouse neonates triggered phosphorylation of EGF receptors (ErbB1 and ErbB2) in the midbrain region, suggesting its penetration through the blood-brain barrier. We repeated EGF administration in postnatal mice and examined synaptic transmission in the VTA with electrophysiological recordings. Subchronic EGF treatment increased the amplitude of field excitatory postsynaptic potentials evoked by stimulation of the anterior VTA. To analyze the EGF effect at a single cell level, dopaminergic neurons were identified by their characteristic hyperpolarizing activated currents in whole cell recording. In these dopaminergic neurons, EGF effects the amplitude of spontaneous miniature excitatory postsynaptic currents (mEPSCs) without affecting their frequency. In agreement, EGF also enhanced the AMPA/NMDA ratio of evoked EPSCs in the dopaminergic neurons. In contrast, EGF effects on mEPSCs of neighboring neurons not exhibiting hyperpolarizing activated currents were modest or insignificant. Thus, these results suggest that circulating EGF substantially influences the physiological properties of developing midbrain dopaminergic neurons in perinatal and postnatal mice.


Transmembrane domain of myelin protein zero can form dimers: possible implications for myelin construction.
Myelin protein zero (MPZ) is the major integral membrane protein of peripheral nerve myelin in higher vertebrates, mediating homoadhesion of the multiple, spiraling wraps of the myelin sheath. Previous studies have shown that full-length MPZ can form dimers and tetramers, and biochemical studies on the extracellular domain (ECD) indicate that it can form a tetramer, albeit very weakly. On the basis of cross-linking studies and equilibrium sedimentation of a transmembrane (TM) domain peptide (MPZ-TM), we find that the MPZ-TM can form homodimers. We further characterized the dimer by measuring the effects of alanine and leucine substitutions on the ability of the TM to dimerize in Escherichia coli membranes. Our results indicate that the primary packing interface for the MPZ TM homodimer is a glycine zipper (GxxxGxxxG) motif. We also find that the G134R mutation, which lies within the glycine zipper packing interface and causes Charcot-Marie-Tooth disease type 1B, severely inhibits dimerization, suggesting that dimerization of the TM domain may be important for the normal functioning of MPZ. By combining our new results with prior work, we suggest a new model for an MPZ lattice that may form during the construction of myelin.


Longitudinal analysis left ventricular chamber responses under durable LVAD support.
Left ventricular assist device (LVAD) support offers remodeling potential in some patients. Our goal was to use noninvasively derived pressure-volume (PV) loops to understand the effect of demographic and device variables on serial changes in cardiac function under pump support. Thirty-two consecutive Medtronic HeartWare Ventricular Assist Device (HVAD) patients (mean 55.9 ± 12.3 years, 81.3% male) were prospectively recruited. Single-cycle ventricular pressure and volume were estimated using a validated algorithm. PV loops (n = 77) and corresponding cardiac chamber dynamics were derived at predefined postimplant timepoints (1, 3, 6 months). Changes in PV loop parameters sustained across the 6-month period were characterized using mixed-effects modeling. The influence of demographic and device variables on the observed changes was assessed. Across a 6-month period, the mean ventricular function parameters remained stable. Significant predictors of monthly improvement of stroke work include: lower pump speeds (2400 rpm vs 2500-2800 rpm) [0.0.051 mm Hg/liter/month (p = 0.001)], high pulsatility index (>1.0 vs <1.0) [0.052 mm Hg/liter/month (p = 0.012)], and ischemic cardiomyopathy indication for LVAD implantation (vs nonischemic) [0.0387 mm Hg/liter/month (p = 0.007)]. Various other cardiac chamber function parameters including cardiac power, peak systolic pressure, and LV elastance also showed improvements in these cohorts. Factors associated with improvement in ventricular energetics and hemodynamics under LVAD support can be determined with noninvasive PV loops. Understanding the basis of increasing ventricular load to optimize myocardial remodeling may prove valuable in selecting eligible recovery candidates.


[PERSONALIZED MEDICINE IN INTERNAL MEDICINE].
Personalized medicine - a new direction in medicine, which is based on the study of various biomarkers and the use of new methods of molecular analysis (primarily evaluating the activity of isoenzymes of cytochrome P450), allowing individualized approach to the selection of both the drugs and the selection of the dosing regimen for the purpose of maximize the effectiveness and safety of pharmacotherapy. This personalized medicine is to change the development and use of preventive and curative interventions. Genetic polymorphism isozymes of cytochrome P450 may determine the individual activity of a particular isozyme, and thus, to predict the clinical effectiveness, and in some cases, the risk of adverse reactions. The article is an example of the use of information on the activity of cytochrome P450 in clinical practice in matters of diagnosis, treatment and prevention of diseases. The scheme of the five best-known activity of isoenzymes of cytochrome P450 is shown.


Pharmacokinetics/pharmacodynamics of acetaminophen analgesia in Japanese patients with chronic pain.
Acetaminophen (APAP) is a popular analgesic. In the present study, we characterized the pharmacokinetics and pharmacodynamics of APAP in the Japanese. Five healthy volunteers were administered 1000 mg of APAP orally. Five patients with chronic pain were administered the optimal oral dose of APAP ranging from 600 to 1000 mg to allow for an adequate analgesic effect. Plasma APAP and APAP metabolite concentrations were measured in the volunteers, plasma APAP concentrations and pain scores using a visual analog scale were measured in the patients with chronic pain. Patient data were fitted to a first-order absorption one-compartment model with delayed effects accounted for by an effect compartment. A sigmoid Emax model was used as the pharmacodynamic model. Acetaminophen-cysteine metabolites, which are conjugates of the toxic metabolite N-acetyl-p-benzoquinone-imine, were detected in the plasma at levels lower than 0.2 microg/ml, but no side effects were observed. The pharmacokinetic and pharmacodynamic parameter (mean+/-S.D.) estimates were as follows: clearance, 18.7+/-4.7 l/h; distribution volume, 30.9+/-6.8 l; absorption rate constant, 2.4+/-1.3 h(-1); rate constant for the elimination of APAP from the effect compartment, 1.3+/-0.5 h(-1); maximum pain relief score, 4.6+/-2.2 units; effect compartment concentration at 50% maximum, 2.0+/-1.2 microg/ml; and sigmoid factor, 1.3+/-0.7. These results suggest that these parameters can be used to determine an effective APAP dosage regimen for Japanese patients with chronic pain.


Fetal heart size measurements as new predictors of homozygous α-thalassemia-1 in mid-pregnancy.
To evaluate the efficacy of using fetal heart size measurements derived from axial echocardiography to predict homozygous α-thalassemia-1. Prospective diagnostic study. The carrier rate of α-thalassemia-1 (-/αα) in China's Guangxi Zhuang Autonomous Region is approximately 15%. If both parents are carriers, the risk of homozygous α-thalassemia-1 in one pregnancy is 25%. Singleton mid-pregnancies at risk of homozygous α-thalassemia-1 were enrolled. Fetal heart measurements, including heart diameter (HD), heart length (HL), heart circumference (HC), and heart area (HA), were measured. The z-scores for these heart parameters were then calculated separately based on previously constructed z-score models. Finally, the accuracy of these predictive variables was analyzed and compared to that achieved by cardiothoracic ratio (CTR) using a receiver operating characteristic (ROC) curves analysis. A total of 214 singleton pregnancies were recruited. The discriminatory power of HA and HD z-scores was better (z-test P< .01) while that of HC and HL z-scores was comparable to (z-test P>.05) that of CTR. HD combined with HA z-scores had the highest sensitivity (100%), and the specificity of HD and/or HA z-scores was 100%. Fetal heart size measurements are novel, effective and noninvasive predictors of homozygosity for α-thalassemia-1 in mid-pregnancy. The discriminatory power of HD and HA z-scores was better than while that of HC and HL z-scores was comparable to that of CTR. Further investigation is needed to understand the effectiveness of these predictors.


Genetic diversity for mycorrhizal symbiosis and phosphate transporters in rice.
Phosphorus (P) is a major plant nutrient and developing crops with higher P-use efficiency is an important breeding goal. In this context we have conducted a comparative study of irrigated and rainfed rice varieties to assess genotypic differences in colonization with arbuscular mycorrhizal (AM) fungi and expression of different P transporter genes. Plants were grown in three different soil samples from a rice farm in the Philippines. The data show that AM symbiosis in all varieties was established after 4 weeks of growth under aerobic conditions and that, in soil derived from a rice paddy, natural AM populations recovered within 6 weeks. The analysis of AM marker genes (AM1, AM3, AM14) and P transporter genes for the direct Pi uptake (PT2, PT6) and AM-mediated pathway (PT11, PT13) were largely in agreement with the observed root AM colonization providing a useful tool for diversity studies. Interestingly, delayed AM colonization was observed in the aus-type rice varieties which might be due to their different root structure and might confer an advantage for weed competition in the field. The data further showed that P-starvation induced root growth and expression of the high-affinity P transporter PT6 was highest in the irrigated variety IR66 which also maintained grain yield under P-deficient field conditions.


A mentally retarded female with distinct facial dysmorphism, joint laxity, clinodactyly and abnormal dermatoglyphics.
We describe a retarded female patient with distinct facial dysmorphism (round puffy cheeks, epicanthal folds, ocular hypertelorism, short broad nose, low set and slanted ears), joint laxity, clinodactyly, abnormal dermatoglyphics (bilateral absence of c palmar triradius and single palmar crease) and a peculiar metacarpophalangeal profile. The possibility of a new MCA/MR is discussed.


[Protective effects of vigabatrin and atropine against dimethoate induced-intoxication in mice].
To investigate the protective effects of vigabatrin and atropine against the acute toxicity of dimethoate in male Kun-min mice. The therapeutic schedules of vigabatrin (50 or 100 mg/kg) and (or) atropine (2.5 or 5.0 mg/kg) were performed according to the L(9) (3(4)) orthogonal test table. The survival time, the righting reflex and the onset of muscle fasciculations were observed after the administration of dimethoate. First, the main effects of vigabatrin, atropine and the interaction between them were statistically significant in the Univariate analysis of the survival time at the alpha level of 0.05 (F(V)= 4.73, P(V)= 0.015, F(A)= 50.88, P(A)= 0.000, F(VxA)= 4.17, P(VxA)= 0.007). The range of atropine was more than double of that of vigabatrin or their interaction (R(A)> 2RV or 2R(VxA)). So not only atropine and vigabatrin but also their combination interaction protected mice against dimethoate lethality. The atropine played the major role in diminishing the lethality induced by dimethoate. Second, only vigabatrin, while not atropine, delayed the mice from dimethoate-induced muscle fasciculation according its statistical results (F(V)= 6.87, P(V)= 0.003, F(A)= 0.03, P(A)= 0.968, F(VxA)= 1.134, P(VxA)= 0.356). It should be noted that vigabatrin could not completely prevent dimethoate induced-muscle fasciculation in the test. At last, both atropine and vigabatrin could maintain the righting reflex in the intoxication, however there was no interaction between them (F(V)= 5.81, P(V)= 0.006, F(A)= 9.05, P(A)= 0.001, F(VxA)= 1.34, P(VxA)= 0.257). Combined treatment with atropine and vigabatrin in the organophosphates intoxication seems reasonable and acceptable.


[Core position of occlusion, gnathology and related diagnosis and treatment principles that mustbe followed in stomatology].
This article discussed, in the following three aspeccts, the standing of occlusion, gnathology and temporomandibular joint (TMJ) in stomatology. And meanwhile highlighted the important meanings for every stomatologists. Firstly, from the history of dentistry or stomatology, the establishment of occlusion and gnathology drived the transformation of dentistry from a craft practice into an independent profession and discipline. Secondly, from the evolution of occlusion, jaw, and TMJ, this article clarified the distinctiveness and uniqueness of occlusion, jaw and TMJ that made modern human beings the most highly endowed. Thirdly, teeth and other oral organs not only have masticatory and digestive functions but also possess more complex social functions. Stomatognathic system is a more accurate conception than oral organs which is usually called. The conception of stomatognathic system gives a clearer sense of wholeness and more beneficial for accurate diagnosis and treatment of occlusion-related diseases as well as temporomandibular disorders. Finally, the author introduced five common examples regarding medical care and patient-doctor relationships in order to further emphasize the significance of the study of occlusion, gnathology and TMJ. It is necessary for not only general stomatoloaists but also other dental specialists in stomatology to clearly understand the principal theories and proficiently master the management capability on occlusion, gnathology and temporomandibular disorders.


Neurotransmitter regulation of MAP kinase signaling in striatal neurons in primary culture.
Glutamate and dopamine are important neurotransmitters in the basal ganglia. Dopamine can act via D1 receptors to activate adenylyl cyclase in striatal neurons, while glutamate stimulation of NMDA receptors leads to an increase in intracellular calcium. Increases in intracellular calcium or cAMP can induce immediate early gene expression in striatal neurons. In the present study, NMDA receptor stimulation or adenylyl cyclase activation resulted in the activation of MAP kinase in striatal neurons in primary culture. The effect of cAMP appeared to involve cAMP-dependent protein kinase, in addition to a tyrosine kinase and MEK. NMDA-induced MAP kinase activation was also dependent on a tyrosine kinase and MEK. The EGF receptor, which has been implicated in calcium- and G protein-induced MAP kinase activation, did not mediate the effects of NMDA or forskolin on MAP kinase. Furthermore, the src kinase inhibitor, herbimycin A, and the phosphoinositol-3-kinase inhibitor, wortmannin, did not prevent MAP kinase activation by these stimuli. However, the ability of both NMDA and forskolin to activate MAP kinase in striatal neurons was blocked by SB 203580, an inhibitor of p38 reactivating kinase. These results indicate that both NMDA receptor activation and elevations in cAMP can result in MEK-induced MAP kinase activation in striatal neurons. However, the signal transduction pathways mediating these responses appear to be distinct from those known to mediate MAP kinase activation by other stimuli.


Thermodynamic assessment of the variation of the surface areas of two synthetic swelling clays during adsorption of water.
Two synthetic smectites (montmorillonite and beidellite) are studied by a water adsorption technique in order to assess their specific surface areas under atmospheric conditions. A route recently proposed for extracting the thermodynamic data from experimental adsorption isotherms is used. The variation of the specific surface area during water adsorption is obtained, which can be linked to the enlargement of the interlayer space determined using X-ray diffraction. This variation is compared to an idealized specific surface area obtained from TEM and X-ray measurements in agreement with crystallographic models. All these results are also compared with those obtained previously for a natural montmorillonite. A simple view of swelling is proposed.


Methicillin-resistant Staphylococcus aureus control at the National University Hospital, Singapore: a historical perspective.
The National University Hospital (NUH) was the first restructured public hospital in Singapore. As the most recently established hospital in Singapore, it has a unique record of alert organisms including methicillin-resistant Staphylococcus aureus (MRSA). We performed a critical review of multiple data sources including surveillance reports, task force reports, published abstracts and manuscripts concerning MRSA in NUH. Three themes emerged: 1) the MRSA rates have remained relatively stable through the life of the hospital despite the increased complexity of patients and intermittent intensified control efforts; 2) the major MRSA task forces were driven by surgeons and 3) a scientific approach to epidemiology has a critical role in understanding and planning interventions. Although containment of MRSA can be accomplished to a certain degree through mobilisation of existing resources, higher goals such as eradication would require massive infusions of infrastructural, scientific and human resources to have a chance of success.


A chemical proteomics approach for global analysis of lysine monomethylome profiling.
Methylation of lysine residues on histone proteins is known to play an important role in chromatin structure and function. However, non-histone protein substrates of this modification remain largely unknown. An effective approach for system-wide analysis of protein lysine methylation, particularly lysine monomethylation, is lacking. Here we describe a chemical proteomics approach for global screening for monomethyllysine substrates, involving chemical propionylation of monomethylated lysine, affinity enrichment of the modified monomethylated peptides, and HPLC/MS/MS analysis. Using this approach, we identified with high confidence 446 lysine monomethylation sites in 398 proteins, including three previously unknown histone monomethylation marks, representing the largest data set of protein lysine monomethylation described to date. Our data not only confirms previously discovered lysine methylation substrates in the nucleus and spliceosome, but also reveals new substrates associated with diverse biological processes. This method hence offers a powerful approach for dynamic study of protein lysine monomethylation under diverse cellular conditions and in human diseases.


The clinical efficacy of cefoperazone-sulbactam versus piperacillin-tazobactam in the treatment of severe community-acquired pneumonia.
The objective was to compare the clinical efficacy of cefoperazone-sulbactam with piperacillin-tazobactam in the treatment of severe community-acquired pneumonia (SCAP). The retrospective study was conducted from March 1, 2018 to May 30, 2019. Clinical outcomes were compared for patients who received either cefoperazone-sulbactam or piperacillin-tazobactam in the treatment of SCAP. A total of 815 SCAP patients were enrolled. Among them, 343 received cefoperazone-sulbactam, and 472 received piperacillin-tazobactam. Patients who received cefoperazone-sulbactam presented with higher Charlson Comorbidity Index scores. (6.20 ± 2.77 vs 5.72 ± 2.61; P = .009). The clinical cure rates and effectiveness for patients receiving cefoperazone-sulbactam and piperacillin-tazobactam were 84.2% versus 80.3% (P = .367) and 85.4% versus 83.3% (P = .258), respectively. In addition, the overall mortality rate of the cefoperazone-sulbactam group was 16% (n = 55), which was also comparable to the piperacillin-tazobactam group (17.8%, n = 84, P = .572). The primary clinical outcomes for patients receiving cefoperazone-sulbactam were superior compared to those receiving piperacillin-tazobactam after adjusting disease severity status. The clinical efficacy of cefoperazone-sulbactam in the treatment of adult patients with SCAP is comparable to that of piperacillin-tazobactam. After adjusting for disease severity, cefoperazone-sulbactam tended to be superior to piperacillin-tazobactam.


Estimation of Spatiotemporal Gait Parameters in Walking on a Photoelectric System: Validation on Healthy Children by Standard Gait Analysis.
The use of stereophotogrammetry systems is challenging when targeting children's gait analysis due to the time required and the need to keep physical markers in place. For this reason, marker-less photoelectric systems appear to be a solution for accurate and fast gait analysis in youth. The aim of this study is to validate a photoelectric system and its configurations (LED filter setting) on healthy children, comparing the kinematic gait parameters with those obtained from a three-dimensional stereophotogrammetry system. Twenty-seven healthy children were enrolled. Three LED filter settings for the OptoGait were compared to the BTS P6000. The analysis included the non-parametric 80% limits of agreement and the intraclass correlation coefficient (ICC). Additionally, normalised limits of agreement and bias (NLoAs and Nbias) were compared to the clinical experience of physical therapists (i.e., assuming an error lower than 5% is acceptable). ICCs showed excellent consistency for most of the parameters and filter settings; NLoAs varied between 1.39% and 12.62%. An inverse association between the number of LEDs for filter setting and the bias values was also observed. Observations confirm the validity of the OptoGait system for the evaluation of spatiotemporal gait parameters in children.


Variations in composition of cartilage from the shoulder joints of young adult dogs at risk for developing canine hip dysplasia.
To determine whether the composition of cartilage from the shoulder joints of dogs varied with the risk of developing canine hip dysplasia (CHD). Observational study. 12 skeletally mature (approx 1 year old) Labrador Retrievers. Dogs were classified as having a low, moderate, or high risk of developing CHD on the basis of distraction indices. Cartilage was harvested from the craniolateral and weight-bearing regions of the humeral heads, and wet weight per unit area and dry, glycosaminoglycan, and fibronectin contents were determined. Glycosaminoglycan and dry contents did not vary among risk groups. For cartilage from the craniolateral region of the humeral head, wet weight per unit area and fibronectin content increased as risk of developing CHD increased. Wet weight and fibronectin content of cartilage from the weight-bearing region of the humeral head did not vary among risk groups. Dogs that have a high risk of developing CHD are also more likely to develop osteoarthritis of the shoulder joint. The observed increases in wet weight per unit area and fibronectin content in cartilage from the craniolateral region of the humeral head in dogs at a high risk of developing CHD may be early sings of incipient osteoarthritis.


A strictly monofunctional bacterial hydroxymethylpyrimidine phosphate kinase precludes damaging errors in thiamin biosynthesis.
The canonical kinase (ThiD) that converts the thiamin biosynthesis intermediate hydroxymethylpyrimidine (HMP) monophosphate to the diphosphate can also very efficiently convert free HMP to the monophosphate in prokaryotes, plants, and fungi. This HMP kinase activity enables salvage of HMP, but it is not substrate-specific and so allows toxic HMP analogs and damage products to infiltrate the thiamin biosynthesis pathway. Comparative analysis of bacterial genomes uncovered a gene, thiD2 , that is often fused to the thiamin synthesis gene thiE and could potentially encode a replacement for ThiD. Standalone ThiD2 proteins and ThiD2 fusion domains are small (~130-residues) and do not belong to any previously known protein family. Genetic and biochemical analyses showed that representative standalone and fused ThiD2 proteins catalyze phosphorylation of HMP monophosphate, but not of HMP or its toxic analogs and damage products such as bacimethrin and 5-(hydroxymethyl)-2-methylpyrimidin-4-ol. As strictly monofunctional HMP monophosphate kinases, ThiD2 proteins eliminate a potentially fatal vulnerability of canonical ThiD, at the cost of the ability to reclaim HMP formed by thiamin turnover.


The Aarhus convention in the nuclear sector-right to information versus nonproliferation?
Nuclear events and problems in siting procedures of nuclear plants poses problems of timely information and the question of proper and trustful information. This paper is divided into three parts. In the first part, the right to information and the Aarhus convention are analysed. The basic rights of the public in the field of environmental matters are presented and discussed. Such rights are also examined through the case law of the European Court of Human Rights. The second part deals with the problem of possible conflicts between the right to information (and environmental information) and obligations from NPT. The third part proposes some solutions to provide a balance between the obligation of giving information and the obligation of protecting certain information under the NPT.


The nsp3 macrodomain promotes virulence in mice with coronavirus-induced encephalitis.
All coronaviruses encode a macrodomain containing ADP-ribose-1"-phosphatase (ADRP) activity within the N terminus of nonstructural protein 3 (nsp3). Previous work showed that mouse hepatitis virus strain A59 (MHV-A59) with a mutated catalytic site (N1348A) replicated similarly to wild-type virus but was unable to cause acute hepatitis in mice. To determine whether this attenuated phenotype is applicable to multiple disease models, we mutated the catalytic residue in the JHM strain of MHV (JHMV), which causes acute and chronic encephalomyelitis, using a newly developed bacterial artificial chromosome (BAC)-based MHV reverse genetics system. Infection of mice with the macrodomain catalytic point mutant virus (N1347A) resulted in reductions in lethality, weight loss, viral titers, proinflammatory cytokine and chemokine expression, and immune cell infiltration in the brain compared to mice infected with wild-type virus. Specifically, macrophages were most affected, with approximately 2.5-fold fewer macrophages at day 5 postinfection in N1347A-infected brains. Tumor necrosis factor (TNF) and interferon (IFN) signaling were not required for effective host control of mutant virus as all N1347A virus-infected mice survived the infection. However, the adaptive immune system was required for protection since N1347A virus was able to cause lethal encephalitis in RAG1(-/-) (recombination activation gene 1 knockout) mice although disease onset was modestly delayed. Overall, these results indicate that the BAC-based MHV reverse genetics system will be useful for studies of JHMV and expand upon previous studies, showing that the macrodomain is critical for the ability of coronaviruses to evade the immune system and promote viral pathogenesis. Coronaviruses are an important cause of human and veterinary diseases worldwide. Viral processes that are conserved across a family are likely to be good targets for the development of antiviral therapeutics and vaccines. The macrodomain is a ubiquitous structural domain and is also conserved among all coronaviruses. The coronavirus macrodomain has ADP-ribose-1"-phosphatase activity; however, its function during infection remains unclear as does the reason that coronaviruses have maintained this enzymatic activity throughout evolution. For MHV, this domain has now been shown to promote multiple types of disease, including hepatitis and encephalitis. These data indicate that this domain is vital for the virus to replicate and cause disease. Understanding the mechanism used by this enzyme to promote viral pathogenesis will open up novel avenues for therapies and may give further insight into the role of macrodomain proteins in the host cell since these proteins are found in all living organisms.