20-HETE increases superoxide production and activates NAPDH oxidase in pulmonary artery endothelial cells.
Reactive oxygen species (ROS) signal vital physiological processes including cell growth, angiogenesis, contraction, and relaxation of vascular smooth muscle. Because cytochrome P-450 family 4 (CYP4)/20-hydroxyeicosatetraenoic acid (20-HETE) has been reported to enhance angiogenesis, pulmonary vascular tone, and endothelial nitric oxide synthase function, we explored the potential of this system to stimulate bovine pulmonary artery endothelial cell (BPAEC) ROS production. Our data are the first to demonstrate that 20-HETE increases ROS in BPAECs in a time- and concentration-dependent manner as detected by enhanced fluorescence of oxidation products of dihydroethidium (DHE) and dichlorofluorescein diacetate. An analog of 20-HETE elicits no increase in ROS and blocks 20-HETE-evoked increments in DHE fluorescence, supporting its function as an antagonist. Endothelial cells derived from bovine aortas exhibit enhanced ROS production to 20-HETE quantitatively similar to that of BPAECs. 20-HETE-induced ROS production in BPAECs is blunted by pretreatment with polyethylene-glycolated SOD, apocynin, inhibition of Rac1, and a peptide-based inhibitor of NADPH oxidase subunit p47(phox) association with gp91. These data support 20-HETE-stimulated, NADPH oxidase-derived, and Rac1/2-dependent ROS production in BPAECs. 20-HETE promotes translocation of p47(phox) and tyrosine phosphorylation of p47(phox) in a time-dependent manner as well as increased activated Rac1/2, providing at least three mechanisms through which 20-HETE activates NADPH oxidase. These observations suggest that 20-HETE stimulates ROS production in BPAECs at least in part through activation of NADPH oxidase within minutes of application of the lipid.


Definition of an immunogenic region within the ovarian tumor antigen stratum corneum chymotryptic enzyme.
The serine protease stratum corneum chymotryptic enzyme (SCCE) is overexpressed by ovarian tumor cells, but is not expressed by normal tissues, suggesting that SCCE may be an attractive target for immunotherapy. In this study, we tested the hypothesis that dendritic cells loaded with SCCE peptides will induce ovarian tumor antigen-specific CD8+ CTL responses and antigen-specific CD4+ helper T cell responses. Computer algorithms were used to identify candidate HLA-A2.1-restricted CD8+ CTL epitopes and HLA-DR-binding CD4+ helper T cell epitopes within SCCE. CD8+ CTL stimulated with peptide-loaded dendritic cells were tested against targets expressing endogenous SCCE, including HLA-A2.1-matched ovarian tumor cells. Dendritic cells were also loaded with an extended SCCE peptide, SCCE 110-139, which encompassed a defined CD8+ CTL epitope and multiple candidate CD4+ T helper cell epitopes. CD8+ CTL specific for SCCE 123-131 lysed autologous macrophages infected with an SCCE-expressing recombinant adenovirus, and also lysed HLA-A2.1-matched, SCCE-expressing ovarian tumor cells. Dendritic cells loaded with SCCE 5-13 peptide stimulated an HLA-A2.1-restricted CD8+ CTL response, but with a reduced level of lysis against ovarian tumor cells. Dendritic cells loaded with SCCE 110-139 induced antigen-specific CD4+ T cell and CD8+ T cell responses. Although SCCE 110-139-loaded dendritic cells processed and presented the 123-131 epitope, the dominant CD8+ CTL response was directed against alternative epitopes within SCCE 110-139. The 110-139 region of SCCE incorporates multiple CD8+ CTL and CD4+ helper T cell epitopes, and represents an attractive target antigen for immunotherapy of ovarian cancer.


Activity patterns and life changes in people with depression.
The Activity Pattern Indicator (API) (Diller, Fordyce, Jacobs, & Brown, 1978) and the Schedule of Recent Experience (SRE) (Holmes, 1981) were used to determine activity patterns and life changes for 15 depressed patients admitted to an acute care mental health unit. Eight categories on the API were correlated with six categories on the SRE to determine the relationship between activity patterns 1 week and 1 month before hospitalization and life changes for the past year. Two correlations indicated that as the total number of life changes and home and family life changes increase, activity related to personal care decreases. Other correlations showed that as life changes related to health, work, and finance increase, such activities as passive recreation, homemaking, socializing, and personal care also increase. Because activity is the cornerstone of occupational therapy, occupational therapists, in treating patients with depression, might include facilitating close inspection of the patients' activity patterns in relation to the changes that have occurred in their lives.


Anti-inflammatory effects of N1-benzyl-4-methylbenzene-1,2-diamine (JSH-21) analogs on nitric oxide production and nuclear factor-kappa B transcriptional activity in lipopolysaccharide-stimulated macrophages RAW 264.7.
N1-Benzyl-4-methylbenzene-1,2-diamine (JSH-21) and its analogs were chemically synthesized and their anti-inflammatory potentials investigated. JSH-21 inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7 in a dose-dependent manner, with an IC50 value of 9.2 microM, where pyrrolidine dithiocarbamate and parthenolide as positive controls exhibited IC50 values of 29.3 and 3.6 microM, respectively. The inhibitory effect of JSH-21 on the NO production was attributable to its down-regulatory action on LPS-inducible NO synthase (iNOS), which was documented by iNOS promoter activity. In the mechanism of the anti-inflammatory action, JSH-21 exhibited inhibitory effects on LPS-induced DNA binding activity and transcriptional activity of nuclear factor-kappa B (NF-kappaB). Structural analogs of JSH-21 also inhibited both the LPS-induced NO production and NF-kappaB transcriptional activity, where diamine substitution at positions 1 and 2 of JSH-21 seems to play an important role in the anti-inflammatory activity.


Improved Normothermic Machine Perfusion After Short Oxygenated Hypothermic Machine Perfusion of Ischemically Injured Porcine Kidneys.
In an era where global kidney shortage has pushed the field of transplantation towards using more marginal donors, modified kidney preservation techniques are currently being reviewed. Some techniques require further optimization before implementation in full scale transplantation studies. Using a porcine donation after circulatory death kidney model, we investigated whether initial kidney hemodynamics improved during normothermic machine perfusion if this was preceded by a short period of oxygenated hypothermic machine perfusion (oxHMP) rather than static cold storage (SCS). Kidneys subjected to 75 minutes of warm ischemia were randomly assigned to either SCS (n = 4) or SCS + oxHMP (n = 4), with a total cold storage time of 240 minutes. Cold preservation was followed by 120 minutes of normothermic machine perfusion with continuous measurement of hemodynamic parameters and renal function. oxHMP preserved kidneys maintained significantly lower renal resistance throughout the normothermic machine perfusion period compared to SCS kidneys (P < 0.001), reaching lowest levels at 60 minutes with means of 0.71 ± 0.35 mm Hg/mL/min/100 g (SCS) and 0.45 ± 0.15 mm Hg/mL/min/100 g (oxHMP). Accordingly, the oxHMP group had a higher mean renal blood flow versus SCS kidneys (P < 0.001). oxHMP kidneys had higher oxygen consumption during normothermic machine perfusion compared to SCS preserved kidneys (P < 0.001). Creatinine clearance remained similar between groups (P = 0.665). Preceding oxHMP significantly improved initial normothermic machine perfusion hemodynamics and increased total oxygen consumption. With the long period of warm ischemia, immediate kidney function was not observed, reflected by the findings of low creatinine clearance in both groups.


Controversies about the use of antidepressants in pregnancy.
There is controversy about the use of antidepressant medication during pregnancy. Decisions about their use are affected by understanding the risks of these medications causing pregnancy loss, congenital malformations, neonatal adaptation syndrome, persistent pulmonary hypertension of the newborn, autism spectrum disorder, or long-term neurocognitive deficits. Although some research has raised concerns about antidepressants causing harm to the fetus and neonate, other studies have disputed these findings or noted that any risks found do not exceed the risk of congenital problems found in 1% to 3% of neonates in the general population. Untreated depression during pregnancy can also cause harm from poor diet, substance abuse, suicidal behavior, or prematurity. Decisions about the use of antidepressants during pregnancy must be based on a risk-benefit analysis based on the best evidence of the risks of treating or not treating maternal depression.


Licensing telemedicine: the need for a national system.
The expansion of information technology has shattered geographic boundaries, allowing for extraordinarily increased access to health information and expanded opportunities for telemedicine practice across state boundaries. But despite its recent growth, telemedicine technology remains embedded in a state-based licensure system that places severe limits on its expansion. The current system of medical licensure is based primarily on statutes written at the turn of the 20th century. This system is inadequate to address the emerging medical practices and future uses of medical technology in the telecommunications age. To respond to the changes offered by the telecommunications revolution, we need to design a new regulatory structure for the 21st century. The purpose of this article is to propose a policy of national telemedicine licensure. The primary goal here is not to simply develop a policy proposal, but to discuss the rationale for national licensure and place it on the policy agenda. A national licensure system will expand the market for telemedicine, promote both the use and development of new technologies, and simultaneously eliminate many of the legal and regulatory ambiguities that plague and constrain the present system.


Genetics of neurodegenerative diseases: an overview.
Genetic factors are central to the etiology of neurodegeneration, both as monogenic causes of heritable disease and as modifiers of susceptibility to complex, sporadic disorders. Over the last two decades, the identification of disease genes and risk loci has led to some of the greatest advances in medicine and invaluable insights into pathogenic mechanisms and disease pathways. Large-scale research efforts, novel study designs, and advances in methodology are rapidly expanding our understanding of the genome and the genetic architecture of neurodegenerative disease. Here, we review major developments in the field to date, highlighting overarching historic trends and general insights. Monogenic neurodegenerative diseases are discussed from the perspectives of both rare Mendelian forms of common disorders, such as Alzheimer disease and Parkinson disease, and heterogeneous heritable conditions, including ataxias and spastic paraplegias. Next, we summarize the experiences from investigations of complex neurodegenerative disorders, including genomewide association studies. In the final section, we reflect upon the limitations of current findings and outline important future directions. Genetics plays an essential role in translational research, ultimately aiming to develop novel disease-modifying therapies for neurodegenerative disorders. We anticipate that individual genetic profiling will also be increasingly relevant in a clinical context, with implications for patient care in line with the proposed ideal of personalized medicine.


The role of viral and host genes in corneal infection with herpes simplex virus type 1.
Herpes simplex virus infection of the eye is the leading cause of blindness due to infection in the US despite the availability of several antiviral drugs. Studies with animal models have shown that three factors, innate host resistance, the host adaptive immune response, and the strain of virus interact to determine whether an infection is asymptomatic or proceeds to the development of blinding keratitis (HSK). Of these, the role of adaptive immunity has received the most attention. This work has clearly shown that stromal keratitis is an immunopathological disease, most likely due to the induction of a delayed type hypersensitivity response. Substantially less is known about the role of specific host genes in resistance to HSK. The fact that different strains of virus display different disease phenotypes indicates that viral 'virulence' genes are critical. Of the 80 plus HSV genes, few have been formally tested for their role in HSV keratitis. Most studies of virulence genes to date have focused on a single gene or protein and large changes in disease phenotypes are usually measured. Large changes in the ability to cause disease are likely to reduce the fitness of the virus, thus such studies, although useful, do not mimic the natural situation. Viral gene products are known to interact with each other, and with host proteins and these interactions are critical in determining the outcome of infection. In reality, the 'constellation' of genes encoded by each particular strain is critical, and how this constellation of genes works together and with host proteins determines the outcome of an infection. The goal of this review is to discuss the current state of knowledge regarding the role of host and viral genes in HSV keratitis. The roles of specific genes that have been shown to influence keratitis are discussed. Recent data showing that different viral genes cooperate to influence disease severity and confirming that the constellation of genes within a particular strain determines the disease phenotype are also discussed, as are the methods used to test the role of viral genes in virulence. It will become apparent that there is a paucity of information regarding the function of many viral genes in keratitis. Improving our knowledge of the role of viral genes is critical for devising more effective treatments for this disease.


[Analysis of scientific information published in Brazil in 5 years on Chagas disease, schistosomiasis, malaria, leishmaniasis and filariasis].
This paper offers a quantitative evaluation of the scientific information produced in Brazil on several endemic diseases: Chagas' disease, schistosomiasis, leishmaniasis, leprosy, malaria and filariasis. The source of data was the Index Medicus Latino Americano (IMLA), and the published scientific information was analyzed in general and specifically, by type of disease and year of publication. The indexed production of articles on the material of the Latin American countries as a whole increased from 3,506 articles in 1978 to 5,528 in 1982 (for an increase of 52.7%), whereas that of Brazil alone rose from 1,781 to 2,531 (an increase of 42.1%) during the same period. The output of articles on endemic diseases totaled 703 papers (6.3% of the total indexed production). Of this total, 441 (62.7%) was on applied research and 262 (37.3%) were on basic research, and these proportions held relatively constant. Chagas' disease and schistosomiasis accounted for 75.2% of that total over the period considered. The production of papers on the diseases of interest grew 79.2%, at the same rate as that of all biomedical information published in Brazil over the period. An equilibrium was reached between the numbers of basic and applied papers. The analysis also identified the core of Brazilian periodicals that most frequently publish information on those endemics. It was also found that a large proportion of articles by Brazilian authors are published in journals of international circulation, and the foreign journals that publish papers by researchers in Brazil were identified.


Dual-crosslinked hydrogel microwell system for formation and culture of multicellular human adipose tissue-derived stem cell spheroids.
Three-dimensional (3D) multicellular spheroids of human adipose tissue-derived stem cells (hASCs) are an attractive system for basic science studies and tissue engineering applications, as they can resemble cellular condensations present in developmental and healing processes. The purpose of this study was to engineer a hydrogel-based microwell platform by capitalizing on the differential swelling behavior of micropatterned dual-crosslinked oxidized, methacrylated alginate (OMA)/multi-arm polyethylene glycol (PEG) hydrogels for rapid formation of uniform multicellular hASC spheroids with controllable size and evaluation of the capacity of the system to be used to drive osteogenic differentiation of the spheroids. By changing the micropattern size, the size of the hydrogel microwells was easily controllable. Microwell-seeded hASCs generated spheroids of relatively uniform size and high cell viability. hASC spheroids exhibited rapid mineralization in osteogenic media, which was faster than that of conventional two-dimensionally cultured hASCs. This new hydrogel microwell system has great potential for controlled multicellular spheroid formation and defined signal presentation from the hydrogel material to the cell aggregates to regulate tissue formation.


Characterizing noise and perceived work environment in a neurological intensive care unit.
The hospital sound environment is complex. Alarms, medical equipment, activities, and ventilation generate noise that may present occupational problems as well as hinder recovery among patients. In this study, sound measurements and occupant evaluations were conducted in a neurological intensive care unit. Staff completed questionnaires regarding psychological and physiological reactions to the sound environment. A-weighted equivalent, minimum, and maximum (L(Aeq),L(AFMin),L(AFMax)) and C-weighted peak (L(CPeak)) sound pressure levels were measured over five days at patient and staff locations. Acoustical descriptors that may be explored further were investigated, including level distributions, restorative periods, and spectral content. Measurements near the patients showed average L(Aeq) values of 53-58 dB. The mean length of restorative periods (L(Aeq) below 50 dB for more than 5 min) was 9 and 13 min for day and night, respectively. Ninety percent of the time, the L(AFMax) levels exceeded 50 dB and L(CPeak) exceeded 70 dB. Dosimeters worn by the staff revealed higher noise levels. Personnel perceived the noise as contributing to stress symptoms. Compared to the majority of previous studies, this study provides a more thorough description of intensive care noise and aids in understanding how the sound environment may be disruptive to occupants.


Coexistence of abnormal systolic motion of mitral valve in a consecutive group of 324 adult Tetralogy of Fallot patients assessed with echocardiography.
The presence of mitral valve prolapse (MVP) in congenital heart disease (CHD) patients is not well described. Tetralogy of Fallot (TOF) is the most common cyanotic CHD associated with overall good long-term survival after palliation. Since MVP is more often identified in adults and TOF patients are now surviving longer, we thus sought to perform this cohort study with a case-control design to (1) determine the prevalence of MVP and systolic displacement of mitral leaflets (SDML) in adult TOF patients, and (2) describe their clinical and imaging characteristics. Retrospective interrogation of our echocardiography database identified 328 consecutive TOF patients ≥18 years from 1 January 2000 to 31 December 2014. All images were reviewed to identify patients with concomitant MVP (prolapse >2 mm beyond the long-axis annular plane) or SDML (<2 mm beyond the annular plane). 26 (8%) TOF patients fulfilled criteria for systolic mitral valve abnormality (SMVA) (15 MVP; 11 SDML). 2 had moderate to severe mitral regurgitation requiring repair. When compared with 52 TOF patients without SMVA, those with SMVA were more likely to be females (60.7% vs 33.9%, p=0.03), less likely to have transannular patch (52% vs 97.4%, p<0.0001), had lower right ventricular ejection fraction (36.5% vs 43.8%, p=0.03) and a trend towards increased risk of atrial (44% vs 30.4%, p=0.5) and ventricular arrhythmias (32% vs 25.5%, p=0.6). On multivariate logistic regression, SMVA was independently associated with the absence of transannular patch (p=0.002) and atrial arrhythmias (p=0.04). In this series of adult TOF patients, we describe a novel finding of a high prevalence of systolic mitral valve abnormalities.


Changing pattern of neonatal bacteremia. Microbiology and antibiotic resistance.
To determine the most important causative agents of bacteremia in a neonatal intensive care unit (NICU); their changing distribution and their antibiotic susceptibility patterns over a 5-year period. This study was performed between January 1997 and January 2001 at the Microbiology Section, Tripoli Medical Center, Tripoli, Libya. During this period 1431 Oxoid Signal Blood Cultures sets were obtained from 1092 NICU with suspected bacteremia. Conventional methods, API 20 E and API 20 NE were used to identify the isolated bacteria. The Kirby-Bauer disk diffusion method was performed to assess their antibiotic susceptibilities in accordance with National Committee for Clinical Laboratory Standards. During the study period, 801 sets out of the total 1431 blood cultures were positive for microbial growth, which represented 648 cases of neonatal bacteremia from a total of 1092 cases. From the total number of isolates, the members of Enterobacteriaceae Serratia, Klebsiella and Enterobacter spp were the most common cause of bacteremia. The coagulase negative and positive Staphylococci were also frequently isolated. A changing pattern of causative pathogen was observed during this study between members of the 3 leading genera of Enterobacteriaceae. Antibiotic susceptibility testing showed a high level of resistance among the most common pathogens. Resistance to aztreonam, imipenem, ciprofloxacin and piperacillin/tazobactam was less frequently encountered. Staphylococcus resistance to anti-staphylococcal antibiotic and due to hyperproduction of penicillinase enzyme was also high and all isolates were remained sensitive to vancomycin. Gram-negative bacteria especially members of the Enterobacteriaceae are important causes of bacteremia in NICUs. Although most isolates remain sensitive to the new antibiotics, emergence of resistant strains cannot be excluded in the future. For that reason, new strategies and continuous surveillance are required to monitor the changing epidemiology of pathogens, antibiotic susceptibilities and antibiotic use needed to overcome the increasing incidence of resistance to conventional drugs.


Hypothesizing in the Face of the Opioid Crisis Coupling Genetic Addiction Risk Severity (GARS) Testing with Electrotherapeutic Nonopioid Modalities Such as H-Wave Could Attenuate Both Pain and Hedonic Addictive Behaviors.
In the United States, amid the opioid overdose epidemic, nonaddicting/nonpharmacological proven strategies are available to treat pain and manage chronic pain effectively without opioids. Evidence supporting the long-term use of opioids for pain is lacking, as is the will to alter the drug-embracing culture in American chronic pain management. Some pain clinicians seem to prefer classical analgesic agents that promote unwanted tolerance to analgesics and subsequent biological induction of the "addictive brain". Reward genes play a vital part in modulation of nociception and adaptations in the dopaminergic circuitry. They may affect various sensory and affective components of the chronic pain syndromes. The Genetic Addiction Risk Severity (GARS) test coupled with the H-Wave at entry in pain clinics could attenuate pain and help prevent addiction. The GARS test results identify high-risk for both drug and alcohol, and H-Wave can be initiated to treat pain instead of opioids. The utilization of H-Wave to aid in pain reduction and mitigation of hedonic addictive behaviors is recommended, notwithstanding required randomized control studies. This frontline approach would reduce the possibility of long-term neurobiological deficits and fatalities associated with potent opioid analgesics.


Epidemiology and natural history of intestinal metaplasia of the gastroesophageal junction and Barrett's esophagus: a population-based study.
Population-based data on the epidemiology and outcomes of subjects with intestinal metaplasia of the gastroesophageal junction (IMGEJ) and Barrett's esophagus (BE) are limited. The objectives of this study were to (i) estimate the incidence of IMGEJ and BE diagnosed from clinically indicated endoscopy in Olmsted County, MN, over three decades (1976-2006) and prevalence as of 1 January 2007, (ii) compare baseline characteristics of subjects with IMGEJ and BE, and (iii) study the natural history and survival of both cohorts. This was a population-based cohort study. The study setting was Olmsted County, MN. Patients with BE (columnar segment >1 cm with intestinal metaplasia) and IMGEJ (intestinal metaplasia in biopsies from the gastroesophageal junction) from 1976 to 2006 in Olmsted County, MN, were identified using Rochester Epidemiology Project resources. Demographic and clinical data were abstracted from medical records and pathology confirmed by gastrointestinal pathologists. The association of baseline characteristics with overall and progression-free survival was assessed using proportional hazards regression models. Outcome measures were baseline characteristics and overall survival of subjects with IMGEJ compared to those with BE. In all, 487 patients (401 with BE and 86 with IMGEJ) were identified and followed for a median interval of 7 (BE subjects) to 8 (IMGEJ subjects) years. Subjects with BE were older, heavier, reported reflux symptoms more often, and had higher prevalence of advanced neoplasia than those with IMGEJ. No patient with IMGEJ progressed to esophageal adenocarcinoma (EAC) in contrast to BE subjects who had a cumulative risk of progression of 7% at 10 years and increased risk of death from EAC (standardized mortality ratio 9.62). The overall survival of subjects with BE and IMGEJ did not differ from that expected in similar age- and sex-distributed white Minnesota populations. Subjects with IMGEJ appear to have distinct clinical characteristics and substantially lower cancer progression risk compared to those with BE.


Maternal factors and experiences associated with observed parenting behavior in mothers attending a residential parenting program.
Parents experiencing early parenting difficulties often seek support through parenting programs. Characteristics of mothers seeking parenting support and information at an early parenting center in Victoria, Australia and the relationships between these factors and parenting behavior were explored using an observational measure of parent-child interaction. Participants were 43 mothers and children attending a 5-day residential parenting program at the Queen Elizabeth Centre. Maternal and sociodemographic data as well as an observational mother-child interaction task from the Nursing Child Assessment Satellite Training Parent Child Interaction Teaching scale were completed and scored on the first day of the program. Certain maternal factors and experiences were associated with observed parenting behavior. Poorer maternal sleeping quality, unplanned pregnancy and preterm birth were all associated with less optimal parenting behavior in certain domains. Findings are discussed with reference to the impact of past experiences around pregnancy and birth as well as the current context and well-being of mothers attending early parenting centers.


A comparison of epineurial, perineurial and epiperineurial methods of nerve suture.
An experimental study was designed to compare the effectiveness of epineurial, perineurial, and combined epineurial and perineurial suture after laceration of the sciatic nerve in rabbits by measuring biochemical determinations in the distal stump of the nerve after both immediate and delayed repairs. Relatively more myelin was found in the immediate epineurial group, which suggests that nerve regeneration was most rapid in this group. Additional experiments are needed to evaluate end-organ reinnervation which is another criterion for evaluating the best method of nerve suture in clinical situations.


[Remedial pedagogic developmental intervention with children displaying psychosocial disorders].
What is the significance of theory of attachment for practical remedial therapeutics? It is a current and intensive debate on this issue in the socio-psychological field of work. The intention of the article is to make public the possible applications of attachment theory. To start with, fundamental assumptions of attachment theory will be introduced (following J. Bowlby 1975), then the role of attachment processes in problematic human relationships will be described. The author will attempt to make clear how fundamental remedial-therapeutic concepts of actual treatment can be deduced from the considerations, theory of attachment makes, and how this can be practically applied, illustrated by a case study from actual remedial-therapeutic work with a girl with psycho-social behavioural difficulties and her mother. Thus, the author tries to show a highly promising way from theory of attachment to attachment therapy.


Inverse regulation of early and late chondrogenic differentiation by oxygen tension provides cues for stem cell-based cartilage tissue engineering.
Multipotent stem/stromal cells (MSC) are considered promising for cartilage tissue engineering. However, chondrogenic differentiation of MSC can ultimately lead to the formation of hypertrophic chondrocytes responsible for the calcification of cartilage. To prevent the production of this calcified matrix at the articular site, the late hypertrophic differentiation of MSCs must be carefully controlled. Given that articular cartilage is avascular, we hypothesized that in addition to its stimulatory role in the early differentiation of chondrogenic cells, hypoxia may prevent their late hypertrophic conversion. Early and late chondrogenic differentiation were evaluated using human adipose MSC and murine ATDC5 cells cultured under either normoxic (21%O2) or hypoxic (5%O2) conditions. To investigate the effect of hypoxia on late chondrogenic differentiation, the transcriptional activity of hypoxia-inducible factor-1alpha (HIF-1α) and HIF-2α were evaluated using the NoShift DNA-binding assay and through modulation of their activity (chemical inhibitor, RNA interference). Results : Our data demonstrate that low oxygen tension not only stimulates the early chondrogenic commitment of two complementary models of chondrogenic cells, but also inhibits their hypertrophic differentiation. Conclusion : These results suggest that hypoxia can be used as an instrumental tool to prevent the formation of a calcified matrix in MSC-based cartilage tissue engineering.


A comparison of British school meals and packed lunches from 1990 to 2007: meta-analysis by lunch type.
Primary school children in the UK have the choice of a school meal provided by the school or a packed lunch provided from home. Currently, more than half of primary school children have a packed lunch. New food-based standards for school meals were introduced in English primary schools in 2006, followed by nutrient-based standards in 2008. No formal comparisons of primary school lunches by lunch type have been undertaken to date. The present review identified seven studies from 1990 to 2007 measuring lunchtime nutrient intake in children aged 5-11 years having a school meal and children having a packed lunch. Pooled estimates for each nutrient were as follows: energy intake was 543 (95 % CI 233, 854) kJ higher in packed lunches; total sugar intake was 14.0 (95 % CI 10.3, 17.7) g higher in packed lunches; non-milk extrinsic sugar intake was 11.7 (95 % CI 7.3, 16.2) g higher in packed lunches; saturated fat intake was 4.7 (95 % CI 2.4, 7.1) g higher in packed lunches and Na intake was 357 (95 % CI 174, 539) mg higher in packed lunches. Differences between school meals and packed lunches were larger for all nutrients after the introduction of food-based standards compared with the period of no standards. However, differences between before and after standards did not reach statistical significance. The nutritional quality of packed lunches is poor compared with school meals. The introduction of food-based standards for school meals in 2006 has moderately improved the nutrient content of school meals, slightly widening the nutritional gap between school meals and packed lunches.


Genome-Wide 5-Formylcytosine Redistribution in KCl-Stimulated Mouse Primary Cortical Neurons is Associated with Neuronal Activity.
An abundant accumulation of DNA demethylation intermediates has been identified in mammalian neurons. While the roles of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in neuronal function have been extensively studied, little is known about 5-formylcytosine (5fC) in neurons. Therefore, this study was to investigate the genome-wide distribution and potential functions of 5fC in neurons. In an in vitro culture model of mouse primary cortical neurons, we observed a dynamic increase in the total 5fC level in the neuronal genome after potassium chloride (KCl) stimulation. Subsequently, we employed chemical-labeling-enabled C-to-T conversion sequencing (CLEVER-seq) to examine the 5fC distribution at a single-base resolution. Bioinformatic analysis revealed that 5fC was enriched in promoter regions, and gene ontology (GO) analysis indicated that the differential formylation positions (DFP) were correlated with neuronal activities. Additionally, integration with previously published nascent RNA-seq data revealed a positive correlation between gene formylation and mRNA expression levels. As well, 6 neuro-activity-related genes with a positive correlation were validated. Furthermore, we observed higher chromatin accessibility and RNA pol II binding signals near the 5fC sites through multiomics analysis. Motif analysis identified potential reader proteins for 5fC. In conclusion, our work provides a valuable resource for studying the dynamic changes and functional roles of 5fC in activated mammalian neurons.


Cigarette smoke induced airway inflammation is independent of NF-κB signalling.
COPD is an inflammatory lung disease largely associated with exposure to cigarette smoke (CS). The mechanism by which CS leads to the pathogenesis of COPD is currently unclear; it is known however that many of the inflammatory mediators present in the COPD lung can be produced via the actions of the transcription factor Nuclear Factor-kappaB (NF-κB) and its upstream signalling kinase, Inhibitor of κB kinase-2 (IKK-2). Therefore the NF-κB/IKK-2 signalling pathway may represent a therapeutic target to attenuate the inflammation associated with COPD. To use a range of assays, genetically modified animals and pharmacological tools to determine the role of NF-κB in CS-induced airway inflammation. NF-κB pathway activation was measured in pre-clinical models of CS-induced airway inflammation and in human lung tissue from COPD patients. This data was complemented by employing mice missing a functional NF-κB pathway in specific cell types (epithelial and myeloid cells) and with systemic inhibitors of IKK-2. We showed in an airway inflammation model known to be NF-κB-dependent that the NF-κB pathway activity assays and modulators were functional in the mouse lung. Then, using the same methods, we demonstrated that the NF-κB pathway appears not to play an important role in the inflammation observed after exposure to CS. Furthermore, assaying human lung tissue revealed that in the clinical samples there was also no increase in NF-κB pathway activation in the COPD lung, suggesting that our pre-clinical data is translational to human disease. In this study we present compelling evidence that the IKK-2/NF-κB signalling pathway does not play a prominent role in the inflammatory response to CS exposure and that this pathway may not be important in COPD pathogenesis.


Effect of diclofenac, ketorolac, and fluorometholone on arachidonic acid metabolites following excimer laser corneal surgery.
To compare the ability of several topical anti-inflammatory agents to modulate the production of prostaglandin E2 after excimer laser ablation in rabbit cornea. Adult New Zealand white rabbits were subjected to phototherapeutic keratectomy with a commercially available excimer laser. Prostaglandin E2 and leukotriene B4 were detected by enzyme-linked immunoassay, and leukocyte infiltration was determined histologically. Prostaglandin E2 and leukocyte infiltration increased in the cornea after excimer ablation. Treatment with topical fluorometholone and diclofenac sodium significantly reduced prostaglandin E2 levels. Corneas treated with diclofenac had significantly higher levels of leukocyte infiltration than those treated with ketorolac tromethamine. No changes in leukotriene B4 levels were detected in this model. As a group, topical anti-inflammatory medications tend to lower prostaglandin E2 levels in rabbit corneas subjected to excimer ablation, but differ in their ability to reduce polymorphonuclear leukocyte infiltration. Further work is needed in this model to understand how these drugs alter leukocyte infiltration of the remaining stromal bed.


Analysis of Genetic Variation and Enhancement of Salt Tolerance in French Pea (Pisum Sativum L.).
Pisum sativum L. (field pea) is a crop of a high nutritional value and seed oil content. The characterization of pea germplasm is important to improve yield and quality. This study aimed at using fatty acid profiling and amplified fragment length polymorphism (AFLP) markers to evaluate the variation and relationships of 25 accessions of French pea. It also aimed to conduct a marker-trait associations analysis using the crude oil content as the target trait for this analysis, and to investigate whether 5-aminolevulinic acid (ALA) could enhance salt tolerance in the pea germplasm. The percentage of crude oil of the 25 pea genotypes varied from 2.6 to 3.5%, with a mean of 3.04%. Major fatty acids in all of the accessions were linoleic acid. Moreover, the 12 AFLP markers used were polymorphic. The cluster analysis based on fatty acids data or AFLP data divided the 25 pea germplasm into two main clusters. The gene diversity of the AFLP markers varied from 0.21 to 0.58, with a mean of 0.41. Polymorphic information content (PIC) of pea germplasm varied from 0.184 to 0.416 with a mean of 0.321, and their expected heterozygosity (He) varied from 0.212 to 0.477 with a mean of 0.362. The AFLP results revealed that the Nain Ordinaire cultivar has the highest level of genetic variability, whereas Elatius 3 has the lowest level. Three AFLP markers (E-AAC/M-CAA, E-AAC/M-CAC, and E-ACA/M-CAG) were significantly associated with the crude oil content trait. The response of the Nain Ordinaire and Elatius 3 cultivars to high salinity stress was studied. High salinity (150 mM NaCl) slightly reduced the photosynthetic pigments contents in Nain Ordinaire leaves at a non-significant level, however, the pigments contents in the Elatius 3 leaves were significantly reduced by high salinity. Antioxidant enzymes (APX-ascorbate peroxidase; CAT-catalase; and POD-peroxidase) activities were significantly induced in the Nain Ordinaire cultivar, but non-significantly induced in Elatius 3 by high salinity. Priming the salt-stressed Nain Ordinaire and Elatius 3 plants with ALA significantly enhanced the pigments biosynthesis, antioxidant enzymes activities, and stress-related genes expression, as compared to the plants stressed with salt alone. In conclusion, this study is amongst the first investigations that conducted marker-trait associations in pea, and revealed a sort of correlation between the diversity level and salt tolerance.


A theoretical quantitative model for evolution of cancer chemotherapy resistance.
Disseminated cancer remains a nearly uniformly fatal disease. While a number of effective chemotherapies are available, tumors inevitably evolve resistance to these drugs ultimately resulting in treatment failure and cancer progression. Causes for chemotherapy failure in cancer treatment reside in multiple levels: poor vascularization, hypoxia, intratumoral high interstitial fluid pressure, and phenotypic resistance to drug-induced toxicity through upregulated xenobiotic metabolism or DNA repair mechanisms and silencing of apoptotic pathways. We propose that in order to understand the evolutionary dynamics that allow tumors to develop chemoresistance, a comprehensive quantitative model must be used to describe the interactions of cell resistance mechanisms and tumor microenvironment during chemotherapy.Ultimately, the purpose of this model is to identify the best strategies to treat different types of tumor (tumor microenvironment, genetic/phenotypic tumor heterogeneity, tumor growth rate, etc.). We predict that the most promising strategies are those that are both cytotoxic and apply a selective pressure for a phenotype that is less fit than that of the original cancer population. This strategy, known as double bind, is different from the selection process imposed by standard chemotherapy, which tends to produce a resistant population that simply upregulates xenobiotic metabolism. In order to achieve this goal we propose to simulate different tumor progression and therapy strategies (chemotherapy and glucose restriction) targeting stabilization of tumor size and minimization of chemoresistance. This work confirms the prediction of previous mathematical models and simulations that suggested that administration of chemotherapy with the goal of tumor stabilization instead of eradication would yield better results (longer subject survival) than the use of maximum tolerated doses. Our simulations also indicate that the simultaneous administration of chemotherapy and 2-deoxy-glucose does not optimize treatment outcome because when simultaneously administered these drugs are antagonists. The best results were obtained when 2-deoxy-glucose was followed by chemotherapy in two separate doses. These results suggest that the maximum potential of a combined therapy may depend on how each of the drugs modifies the evolutionary landscape and that a rational use of these properties may prevent or at least delay relapse. This article was reviewed by Dr Marek Kimmel and Dr Mark Little.


Silver sulfadiazine for control of burn wound infections.
Silver sulfadiazine (Silvadene, U.S.; Flamazine, U.K.; Flammazine, N.; Sulplata, S.A.) is the newest topical antimicrobial agent available following worldwide clinical trials. Good control of infection is achieved without pain or other demonstrable side effects, using either dressings or the exposure technic. Many burned areas kept free of infection heal without grafting. Where necessary, early preparation for and good take of grafts has been attained by utilizing this new therapeutic agent. Markedly reduced mortality from burn wound sepsis has generally been observed.


Suitability of MRF Recovered Post-Consumer Polypropylene Applications in Extrusion Blow Molded Bottle Food Packaging.
Polypropylene (PP) is one of the most abundant plastics used due to its low price, moldability, temperature and chemical resistance, and outstanding mechanical properties. Consequently, waste from plastic materials is anticipated to rapidly increase with continually increasing demand. When addressing the global problem of solid waste generation, post-consumer recycled materials are encouraged for use in new consumer and industrial products. As a result, the demand is projected to grow in the next several years. In this study, material recovery facility (MRF)-recovered post-consumer PP was utilized to determine its suitability for extrusion blow molded bottle food packaging. PP was sorted and removed from mixed-polymer MRF-recovered bales, ground, trommel-washed, then washed following the Association of Plastics Recyclers' protocols. The washed PCR-PP flake was pelletized then manually blended with virgin PP resin at 25%, 50%, 75, and 100% PCR-PP concentrations and fed into the extrusion blow molding (EBM) machine. The EBM bottles were then tested for physical performance and regulatory compliance (limits of TPCH: 100 μg/g). The results showed an increased crystallization temperature but no practical difference in crystallinity as a function of PCR-PP concentrations. Barrier properties (oxygen and water vapor) remained relatively constant except for 100% MRF-recovered PCR-PP, which was higher for both gas types. Stiffness significantly improved in bottles with PCR-PP (p-value < 0.05). In addition, a wider range of N/IAS was detected in PCR-PP due to plastic additives, food additives, and degradation byproducts. Lastly, targeted phthalates did not exceed the limits of TPCH, and trace levels of BPA were detected in the MRF PCR-PP. Furthermore, the study's results provide critical information on the use of MRF recovered in food packaging applications without compromising performance integrity.


Association of estrogen receptor alpha gene polymorphism with age at onset, general psychopathology symptoms, and therapeutic effect of schizophrenia.
Estrogen is believed to play an important role in the central nervous system (CNS) and exert a protective role against schizophrenia. Estrogen receptor alpha (ESRα) mediates the biological action of estrogen. Rs2234693 and rs9340799, single nucleotide polymorphisms of ESRα, may be related to many psychiatric disorders, while their association with schizophrenia has not been clarified. Genotypes rs2234693 and rs9340799 were detected in 303 schizophrenic patients and 292 healthy controls in a Chinese population. The positive and negative syndrome scale (PANSS) was used to estimate symptoms and therapeutic effects. The association of these polymorphisms with schizophrenia and clinical characteristics was analyzed by the chi-square test, analysis of variance, and others. The distribution of genotypes and allele frequencies of rs2234693 and rs9340799 exhibited no significant differences between patients and controls, while haplotypes consisting of these polymorphisms had significant differences. For 2234693, T-allele carriers had an earlier age at onset. CC-homozygote carriers had a higher general psychopathology score and its percentage reduction in male and paranoid patients, respectively. CC-homozygote carriers had a higher tension (G4) and poor impulse control (G14) score, mainly in paranoid patients. Furthermore, patients with the CC homozygote had higher reductions of G4 and G14 scores when treated by aripirazole and risperidone, respectively. Haplotypes consisting of these two polymorphisms in ESRα may be strongly associated with schizophrenia. The rs2234693 was related to age at onset, general psychopathology, G4 and G14 symptoms, even the therapeutic effect in different groups.


Outcome assessment in emergency medicine--a beginning: results of the Council of Emergency Medicine Residency Directors (CORD) emergency medicine consensus workgroup on outcome assessment.
This article is designed to serve as a guide for emergency medicine (EM) educators seeking to comply with the measurement and reporting requirements for Phase 3 of the Accreditation Council for Graduate Medical Education (ACGME) Outcome Project. A consensus workshop held during the 2006 Council of Emergency Medicine Residency Directors (CORD) "Best Practices" conference identified specific measures for five of the six EM competencies--interpersonal communication skills, patient care, practice-based learning, professionalism, and systems-based practice (medical knowledge was excluded). The suggested measures described herein should allow for ease in data collection and applicability to multiple core competencies as program directors incorporate core competency outcome measurement into their EM residency training programs.


Dependence of ionized and total Ca in squid axons on Nao-free or high-Ko conditions.
The level of intracellular Ca in squid axons (both ionized and total Ca) was studied as a function of the experimental variables [Na]i, [Na]o, pHi, cyanide, and depolarization. Ionized Ca was measured by following the light emission of aequorin while total Ca was measured by the atomic absorption analysis of samples of axoplasm. Aequorin glow is known to be increased either by the application of Nao-free solutions or by depolarization produced by external solutions containing greater than normal K concentrations. The present results show that if [Na]i is low, the depolarization that is brought about by solutions with elevated [K] leads to a resting light emission that is decreased rather than increased, as is the case when [Na]i is high. In axons where [Na]i is varied, a comparison of the increments in light emission produced by the application first of Na-free and then of high-K solutions shows that they have an identical dependence on [Na]i, with a half-activation of Ca entry produced by an [Na]i of 25-30 mM. Changes in pHi affect the aequorin signal produced by depolarization, with acidification reducing and alkanization increasing the response. Cyanide did not greatly affect the size of the signal resulting from either Nao removal or that from depolarization.


N-terminal functional region of the invariant chain efficiently targets the binding of a CTL epitope to MHC class I molecules during cross-presentation.
Cross-presentation (CP) is important for priming T cell responses to many viral, bacterial, and tumor antigens. Here, we designed two Ii mutants, based on evidence that the invariant chain (Ii, also named CD74) binds newly synthesized MHC class I molecules with the class II-associated invariant chain peptide (CLIP) region of Ii, which occupies the peptide-binding groove. Specifically, we designed (1) Ii-O257, which is a CLIP-substituted Ii chimer, in which OVA257-264 (SIINFEKL) was substituted for CLIP, and (2) Ii-, also named CT257, which is a C-terminal truncated form of Ii-O257 that contains the N-terminal flanking region of Ii. We immunized C57BL/6 mice with these recombinant proteins. Real-time PCR detected that mice immunized with either Ii-O257 or Ii-CT257 recombinant proteins exhibited increased IFN-γ mRNA expression (approximately 11-fold and 13-fold, respectively) and increased IL-2 mRNA expression (approximately 9-fold and 11-fold, respectively), compared to mice immunized with the OVA257-264 peptide. In vivo cytokine analysis showed that recombinant Ii proteins were highly efficient at activating T cells. Confocal microscopy and co-immunoprecipitation showed that the 2 Ii-OVA257-264 chimers are associated intracellularly with H-2K(b) molecules. Thus, Ii-CT257 (amino acids 1-89) binds stably to MHC class I with high affinity, indicating that it is a minimal functional fragment of the Ii immune vector. In conclusion, the N-terminal functional region of the Ii fusion protein containing CTL epitopes might prove to be useful for developing peptide or DNA vaccines that use CP as the main mechanism for CD8(+) T cell stimulation.


Elevated Expression of Chemokine CXCL13 in Chronic Hepatitis B Patients Links to Immune Control during Antiviral Therapy.
C-X-C-chemokine ligand 13 (CXCL13), the ligand for C-X-C chemokine receptor type 5 (CXCR5), is a major regulator of B-cell trafficking and plays an integral role in age-dependent clearance of hepatitis B virus (HBV) in the mouse model. However, the expression and function of CXCL13 in patients with chronic hepatitis B (CHB) remain unknown. By use of liver cell subpopulations isolated from CHB patients, we found that CXCL13 mRNA was abundantly expressed in Kupffer cells (KCs), but not in primary hepatocytes, liver sinusoidal endothelial cells, and hepatic stellate cells. Interestingly, KC isolated from HBV-positive liver had much higher level of CXCL13 expression than non-HBV-infected controls. And its expression was induced by toll-like receptor 3 ligand poly I:C stimulation. Moreover, intense expression of CXCL13 protein and accumulation of CD4+ T and B cells were evident in follicular-like structures in the liver tissue of CHB patients, which indicated its chemotactic effect on CXCR5+ CD4+ cells and B cells. Consistently, the levels of serum CXCL13 were significantly higher in the CHB patients than in healthy controls. Furthermore, CXCL13 concentration was increased in the complete response (CR) group during weeks 0-12 and did not change significantly during the course of telbivudine treatment, compared with the patients who didn't achieve CR. In conclusion, the HBV-related increase of CXCL13 production in KC and serum CXCL13 level during telbivudine treatment might be associated with immune control of chronic HBV infection.


Hypoxia-induced myeloid derived growth factor promotes hepatocellular carcinoma progression through remodeling tumor microenvironment.
Purpose: Exploring and studying the novel target of hepatocellular carcinoma (HCC) has been extremely important for its treatment. The principal objective of this project is to investigate whether myeloid derived growth factor (MYDGF) could accelerate the progression of HCC, and how it works. Methods: Cell proliferation, clonal formation, sphere formation and xenograft tumor experiments were used to prove the critical role of MYDGF in HCC progression. Tumor angiogenesis, immune cell infiltration, macrophage chemotaxis and inflammatory cytokines detection were utilized to clarify how MYDGF remodeled the tumor microenvironment (TME) to accelerate the progress of HCC. Results: Here, we reported a secretory protein MYDGF, which could be induced by hypoxia, was significantly upregulated in HCC and associated with poor clinical outcomes. Using bioinformatics and experimental approaches, we found that MYDGF promotes cell proliferation in vitro and in vivo through a mechanism that might involve enhanced self-renewal of liver CSCs. Furthermore, MYDGF can also promote tumor angiogenesis, induce macrophages to chemotaxis into tumor tissue, and then release various inflammatory cytokines, including IL-6 and TNF-α, which ultimately aggravate inflammation of tumor microenvironment and accelerate HCC progression. Conclusions: We provided evidence that MYDGF could directly affect the self-renewal of liver CSCs, and indirectly aggravate the inflammatory microenvironment to accelerate the progression of HCC.


Use of pre-travel vaccine-preventable disease serology as a screening tool to identify patients in need of pre-travel vaccination: a retrospective audit.
Vaccination is a safe and effective public health intervention that not only protects individual travellers from vaccine-preventable diseases (VPDs), but prevents them from becoming a source of disease in their destination and on their return. Obtaining an accurate vaccination history from travellers during a pre-travel review can be difficult; serology may be used to identify patients who are non-immune to specific diseases in order to guide vaccination requirements. Clinically relevant data about the usefulness of serology in this setting are lacking. We performed a retrospective audit of pre-travel VPD serology requested by practitioners of a busy community-based travel clinic. All serological results for measles, mumps, rubella, varicella zoster virus, hepatitis A and B requested over a 5-year period were extracted and analysed. Results were stratified by gender and year of birth and compared using Stata. Four thousand four hundred and fifty-one serological assays from 1445 individual were assessed. Overall, 47% of patients tested had at least one negative serological result. High rates of seropositivity for measles, mumps and rubella were seen in those born prior to 1966 but >10% of travellers born after 1966 lacked serological evidence of protection against these diseases. Hepatitis A and B serological results revealed broadly lower rates of immunity in our community likely reflecting the absence of these vaccines from historical vaccine protocols. Serology can be a useful tool in the identification of non-immune travellers to enable targeted vaccination prior to travel. We recommend that travel health clinicians assess patients' vaccination and infection histories, and strongly consider serology or vaccination where there is doubt about immunity. This will help protect the traveller and prevent importation of disease into destination or home communities.


Secretion-Based Modes of Action of Biocontrol Agents with a Focus on Pseudozyma aphidis.
Plant pathogens challenge our efforts to maximize crop production due to their ability to rapidly develop resistance to pesticides. Fungal biocontrol agents have become an important alternative to chemical fungicides, due to environmental concerns related to the latter. Here we review the complex modes of action of biocontrol agents in general and epiphytic yeasts belonging to the genus Pseudozyma specifically and P. aphidis in particular. Biocontrol agents act through multiple direct and indirect mechanisms, which are mainly based on their secretions. We discuss the direct modes of action, such as antibiosis, reactive oxygen species-producing, and cell wall-degrading enzyme secretions which can also play a role in mycoparasitism. In addition, we discuss indirect modes of action, such as hyperbiotrophy, induced resistance and growth promotion based on the secretion of effectors and elicitors from the biocontrol agent. Due to their unique characteristics, epiphytic yeasts hold great potential for use as biocontrol agents, which may be more environmentally friendly than conventional pesticides and provide a way to reduce our dependency on fungicides based on increasingly expensive fossil fuels. No less important, the complex mode of action of Pseudozyma-based biocontrol agents can also reduce the frequency of resistance developed by pathogens to these agents.


Optical 4x4 hitless slicon router for optical networks-on-chip (NoC).
We demonstrate here a spatially non-blocking optical 4x4 router with a footprint of 0.07 mm(2) for use in future integrated photonic interconnection networks. The device is dynamically switched using thermo-optically tuned silicon microring resonators with a wavelength shift to power ratio of 0.25nm/mW. The design can route four optical inputs to four outputs with individual bandwidths of up to 38.5 GHz. All tested configurations successfully routed a single-wavelength laser and provided a maximum extinction ratio larger than 20 dB.


Point of care tests for invasive fungal infections: a blueprint for increasing availability in Africa.
Invasive fungal infections (IFIs) such as cryptococcosis, disseminated histoplasmosis, and chronic pulmonary aspergillosis are significant causes of morbidity and mortality in Africa. Lack of laboratory infrastructure and laboratory personnel trained in diagnostic mycology hamper prompt detection and management of IFIs on the continent. Point-of-care tests (POCT) obviate the need for complex infrastructure, skilled technicians, and stable electricity and have had major impacts on the diagnosis of bacterial, viral, and parasitic infections in low- and middle-income countries. Over the last 10 years, POCTs for IFIs have become increasingly available and they have the potential to revolutionize the management of these infections if scaled up in Africa. At the beginning of 2021, the World Health Organization (WHO) Essential Diagnostic List (EDL) included a cryptococcal antigen test for the diagnosis of cryptococcosis, Histoplasma antigen test for the diagnosis of disseminated histoplasmosis, and Aspergillus-specific test for the diagnosis of chronic pulmonary aspergillosis. All of these are available in formats that may be used as POCTs and it is hoped that this will improve the diagnosis of these life-threatening IFIs, especially in low- and middle-income countries. This perspective review discusses commercially available POCTs and outlines strategies of a blueprint to achieve their roll-out in Africa. The strategies include raising awareness, conducting research that uncovers the exact burden of IFIs, increasing advocacy, integrating diagnosis of IFIs into existing public health programs, adoption of the WHO EDL at country levels, and improving logistics and supply chains.


Pap Smear Screening Participation Behavior and Related Factors in Married Immigrant Women.
This study's aim was to investigate participation in Pap smear screening among married immigrant women and their behavior and its related factors. A survey was conducted among 165 married immigrant women in Gyeongsangnam-do from January 1 to March 20, 2010. Results in this study showed that 51.5% have never participated in Pap Smear screening. Among those who have participated in the Pap Smear screening, 10.9% had regular screening, while 37.6% had irregular screening. Pap smear screening behavior was significantly different according to the experiences in health checkup (chi-square=34.009, p<.001) , whether or not there was a hospital the woman regularly visited (chi-square=7.768, p=.021) and perceived barriers (F=3.214, p=.043). For improvement of Pap smear participation, this study proposes to develop various nursing intervention programs which can improve perceived barriers in regards to the related variables. In addition, it is necessary to come up with a strategy to advertise the participation in Pap smear screening in a systematic and continuous manner in order to raise womens' awareness and to make married immigrant women realize the importance of regular Pap smear screenings.


[Dynamics of monosynaptic response potentiation after nerve section at different distances from the spinal cord].
The nature of increase in amplitude of monosynaptic reaction of the anterior root to stimulation of the posterior root was studied in 18, 24 and 48 hrs after preliminary cutting of the sciatic nerve in rats. After a close to spinal cord nerve cutting the amplitude of monosynaptic reaction on the side of the cutting increased within 18 hrs whereas after the distant cutting the monosynaptic reaction increase only occurred within 24 hrs. The increase in sensitivity to nerve impulses of the partially deafferented motoneurons is due not to the switching off the background impulsation but to the impairment of the nonimpulse influence on motoneurons.


Desulfopila aestuarii gen. nov., sp. nov., a Gram-negative, rod-like, sulfate-reducing bacterium isolated from an estuarine sediment in Japan.
A strictly anaerobic, mesophilic, sulfate-reducing bacterial strain (MSL86(T)) isolated from an estuarine sediment in the Sea of Japan (around the Japanese islands) was characterized phenotypically and phylogenetically. The cells were found to be Gram-negative, motile, non-spore-forming rods. Catalase was not detected. The optimum NaCl concentration for growth was 1.0 % (w/v) and the optimum temperature was 35 degrees C. Strain MSL86(T) was slightly alkaliphilic, with optimum growth at pH 7.5-7.6. Organic electron donors were incompletely oxidized to (mainly) acetate. Strain MSL86(T) utilized formate, pyruvate, lactate, fumarate, ethanol, propanol, butanol and glycerol as electron donors for sulfate reduction and did not use acetate, propionate, butyrate, succinate, malate, methanol, glycine, alanine, serine, aspartate, glutamate or H(2). Sulfite, thiosulfate and fumarate were used as electron acceptors with lactate as an electron donor. Without electron acceptors, the strain fermented pyruvate and fumarate. The genomic DNA G+C content was 54.4 mol%. Menaquinone MK-8(H(4)) was the major respiratory quinone. The major cellular fatty acids were C(16 : 0), C(16 : 1)omega7, C(16 : 1)omega5 and C(17 : 1)omega6. A phylogenetic analysis based on the 16S rRNA gene sequence placed the strain in the class Deltaproteobacteria. The recognized bacterium most closely related to strain MSL86(T) was [Desulfobacterium] catecholicum DSM 3882(T) (sequence similarity 94.4 %), and the next most closely related recognized species were Desulfotalea psychrophila (94.2 % sequence similarity with the type strain) and Desulfotalea arctica (93.7 %). As the physiological and chemotaxonomic characteristics of MSL86(T) were distinctly different from those of any related species, a novel genus and species Desulfopila aestuarii gen. nov., sp. nov. are proposed to accommodate the strain. The type strain of Desulfopila aestuarii is MSL86(T) (=JCM 14042(T)=DSM 18488(T)).


Verification of the linac isocenter for stereotactic radiosurgery using cine-EPID imaging and arc delivery.
Verification of the mechanical isocenter position is required as part of comprehensive quality assurance programs for stereotactic radiosurgery/radiotherapy (SRS/SRT) treatments. Several techniques have been proposed for this purpose but each of them has certain drawbacks. In this paper, a new efficient and more comprehensive method using cine-EPID images has been introduced for automatic verification of the isocenter with sufficient accuracy for stereotactic applications. Using a circular collimator fixed to the gantry head to define the field, EPID images of a Winston-Lutz phantom were acquired in cine-imaging mode during 3600 gantry rotations. A robust MATLAB code was developed to analyze the data by finding the center of the field and the center of the ball bearing shadow in each image with sub-pixel accuracy. The distance between these two centers was determined for every image. The method was evaluated by comparison to results of a mechanical pointer and also by detection of a manual shift applied to the phantom position. The repeatability and reproducibility of the method were tested and it was also applied to detect couch and collimator wobble during rotation. The accuracy of the algorithm was 0.03 +/- 0.02 mm. The repeatability was less than 3 pm and the reproducibility was less than 86 microm. The time elapsed for the analysis of more than 100 cine images of Varian aS1000 and aS500 EPIDs were approximately 65 and 20 s, respectively. Processing of images taken in integrated mode took 0.1 s. The output of the analysis software is printable and shows the isocenter shifts as a function of angle in both in-plane and cross-plane directions. It gives warning messages where the shifts exceed the criteria for SRS/SRT and provides useful data for the necessary adjustments in the system including bearing system and/or room lasers. The comprehensive method introduced in this study uses cine-images, is highly accurate, fast, and independent of the observer. It tests all gantry angles and is suitable for pretreatment QA of the isocenter for stereotactic treatments.


The novel two-dimensional photocatalyst SnN3 with enhanced visible-light absorption for overall water splitting.
Herein, we proposed a novel excellent two-dimensional photocatalyst, the SnN3 monolayer, using first-principles calculations. The stability of the SnN3 monolayer was examined via formation energy, phonon spectroscopy and ab initio molecular dynamics simulations. The SnN3 monolayer has an ultra-high optical absorption capacity of the order of 105 cm-1 in the visible region, which is 3, 4 and 10 times those of SnP3, MoS2 and g-C3N4 monolayers, respectively. Moreover, it has a higher carrier mobility, 769.19 cm2 V-1 s-1, than the other monolayers; the available electrostatic potential of -5.02 eV and the appropriate band gap of 1.965 eV indicate its applicability as a catalyst for overall water splitting over a wide strain range. The electronic properties of the SnN3 monolayer could also be engineered effectively by altering the external strain and electric field.


Gender difference in the impact of Ischaemic heart disease on heart failure.
Although the impact of ischaemic heart disease (IHD) on heart failure (HF) is evolving, there is uncertainty about the role of IHD in determining the risk of clinical outcomes by gender. This study evaluated the gender difference in the impact of IHD on long-term clinical outcomes in patients with heart failure reduced ejection fraction (HFrEF). Study data were obtained from a nationwide registry, which is a prospective multicentre cohort that included 3200 patients who were hospitalized for HF. A total of 1638 patients with HFrEF were classified by gender. The primary outcome was all-cause death during follow-up. In total, 133 women (18.9%) died and 168 men (18.0%) died during the follow-up (median, 489 days). Women with HFrEF with IHD had a significantly lower cumulative survival rate than women without IHD at the long-term follow-up (74.8% vs 84.9%, log-rank P = .001). However, the survival rate was not different in men with HFrEF with IHD compared with men without IHD. A Cox regression analysis showed that IHD had a 1.43-fold increased risk for all-cause mortality independently in women after adjusting for confounding factors (odds ratio 1.43, 95% confidence interval 1.058-1.929, P = .020). Ischaemic heart disease was an independent risk factor for long-term mortality in women with HFrEF. IHD should be actively evaluated in women with HF for predicting clinical outcomes and initiating appropriate treatment. Women with HF caused by IHD should be treated more meticulously to avoid a poor prognosis.


Models of neuronal transient synchrony during propagation of activity through neocortical circuitry.
Stereotypic paroxysmal discharges that propagate in neocortical tissues after electrical stimulations are used as a probe for studying cortical circuitry. I use modeling to investigate the effects of sparse connectivity, heterogeneity of intrinsic neuronal properties, and synaptic noise on synchronization of evoked propagating neuronal discharges in a network of excitatory, regular spiking neurons with spatially decaying connectivity. The global coherence of the traveling discharge is characterized by the correlation function between spike trains of neurons, averaged over all the pairs of neurons in the system at the same distance. Local coherence of two neurons is characterized by their correlation function averaged over many trials or, for persistent activity, over a long time interval. Spike synchronization between neurons emerges as a result of the transient activity; if activity is persistent, there is no synchrony, and cross-correlation functions are flat. During discharge propagation, system-average cross-correlation between neurons does not depend on their mutual distance except for a time shift. Spike synchronization occurs only when the average number of synapses M a cell receives is large enough. As M increases, there is a cross-over from an asynchronized to a synchronized discharge. Synaptic depression appears to help synchrony; it reduces the M value at the cross-over. The strengths of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) conductances affect synchrony only weakly. Spike synchronization is robust even with large levels of heterogeneity. Synaptic noise reduces synchrony, but strong synchrony is observed at a noise level that cannot evoke spontaneous discharges. System-average spike synchronization is determined by the levels of sparseness, heterogeneity, and noise, whereas trial-average spike synchronization is determined only by the noise level. Therefore, I predict that experiments will reveal local, two-cell spike synchrony, but not global synchrony.


A central role for R7bp in the regulation of itch sensation.
Itch is a protective sensation producing a desire to scratch. Pathologic itch can be a chronic symptom of illnesses such as uremia, cholestatic liver disease, neuropathies and dermatitis, however current therapeutic options are limited. Many types of cell surface receptors, including those present on cells in the skin, on sensory neurons and on neurons in the spinal cord, have been implicated in itch signaling. The role of G protein signaling in the regulation of pruriception is poorly understood. We identify here 2 G protein signaling components whose mutation impairs itch sensation. R7bp (a.k.a. Rgs7bp) is a palmitoylated membrane anchoring protein expressed in neurons that facilitates Gαi/o -directed GTPase activating protein activity mediated by the Gβ5/R7-RGS complex. Knockout of R7bp diminishes scratching responses to multiple cutaneously applied and intrathecally-administered pruritogens in mice. Knock-in to mice of a GTPase activating protein-insensitive mutant of Gαo (Gnao1 G184S/+) produces a similar pruriceptive phenotype. The pruriceptive defect in R7bp knockout mice was rescued in double knockout mice also lacking Oprk1, encoding the G protein-coupled kappa-opioid receptor whose activation is known to inhibit itch sensation. In a model of atopic dermatitis (eczema), R7bp knockout mice showed diminished scratching behavior and enhanced sensitivity to kappa opioid agonists. Taken together, our results indicate that R7bp is a key regulator of itch sensation and suggest the potential targeting of R7bp-dependent GTPase activating protein activity as a novel therapeutic strategy for pathological itch.


Gender influences treatment and survival in colorectal cancer surgery.
It has been observed that survival after colorectal cancer resection is longer in women than men. The majority of these studies are in non-U.S. populations and few use appropriate multivariate adjustment. We used the Surveillance, Epidemiology and End Results- Medicare database to examine disease-specific survival in women and men undergoing colorectal cancer resection in the United States, adjusting for patient, cancer, and hospital characteristics in an effort to identify disparities, not only in survival, but also in patterns of presentation, surgical resection, and treatment. With use of the Surveillance, Epidemiology and End Results-Medicare-linked database, we performed a retrospective cohort study of 30,975 patients with colon cancer and 8,350 patients with rectal cancer who underwent surgical resection from 1996 to 2003. Kaplan-Meier curves, the log-rank test, and Cox regression compared survival between genders. Multivariate adjustment was performed by use of patient demographics; cancer variables including stage, medical treatment, and adequacy of nodal harvest; and hospital characteristics. In both cancers, women presented at an older age and more emergently than men. They also underwent less aggressive medical therapy for advanced disease; in particular, in the octogenarian population. In unadjusted analysis, there was no gender difference in survival (colon hazard ratio, 0.98; P = 0.74; rectal hazard ratio, 0.95; P =0.10). After full adjustment, however, women had significantly longer survival, in particular, after rectal resection (colon hazard ratio, 0.91; P< 0.001; rectal hazard ratio, 0.82; P< 0.001). Women in this cohort have longer adjusted survival compared with men; however, they present more emergently and at an older age, and they receive less aggressive medical treatment. These are noticeable disparities that could serve as targets for continued improvement.


Human Papillomavirus Investigation in Head and Neck Squamous Cell Carcinoma: Initial Report from the Low Risk HPV Types Associations
Background: Head and neck squamous cell carcinomas (HNSCC) are a major health issue in many parts of the world. Recently, attention has focused on the human papilloma virus (HPV) as a potential causative agent for HNSCC. This study aimed to survey HPV occurrence in HNSCCs as part of a comprehensive molecular epidemiology approach. Methods: In this retrospective study, patients were recruited from hospitals affiliated to the Iran University of Medical Sciences, Tehran, Iran. Formalin-fixed paraffin-embedded (FFPE) blocks were subjected to DNA isolation by QIAamp® DNA FFPE Tissue Kit and nested PCR, HPV-16 specific conventional PCR, and extra INNO-LiPA HPV genotyping assays were subsequently performed. PCR products were purified with a High Pure PCR Product Purification Kit and sequenced with an ABI 3730 XL sequencer. CLC Main Workbench 5 and MEGA5 bioinformatics software was used to analyze the raw data and to create the phylogenetic tree. SPSS v.20 was applied for statistical analysis. Results: A total of 156 FFPE blocks were collected from 2011 to 2017. Total mean age (y) of participants was 60.5 ± 12.6; 77.6 % (121/156) being men and 22.4% (35/156) e women. Overall, 5/156 (3.2%) patients (3 females and 2 males) were found to be HPV positive using the three methods. HPV genotyping revealed HPV types 16, 2, 27, and 43 in these malignancies. Tumor location and lymph node involvement indicated significant differences between the sexes. Conclusion: Although high risk HPV genotypes have been associated with HNSCCs, our findings indicate a potential of low risk HPV types to also contribute to such malignancies.


Observed and Modeled Seasonal Air Quality and Respiratory Health in Senegal During 2015 and 2016.
In this work, we use existing particulate matter (PM) data from Dakar, Senegal, satellite aerosol optical depth (AOD) and the Weather Research and Forecasting (WRF) model to evaluate the role of dust transport from the Sahara and PM concentrations and exposure into other administrative districts of Senegal during 2015 and 2016. We also use data from the Ministry of Health to examine spatial and temporal patterns of acute respiratory infections, asthma, bronchitis, and tuberculosis across Senegal with an emphasis on Northern Hemisphere winter December-February, when air quality is poor, and June-August when there is an improvement in air quality. Measurements in Dakar, Senegal, suggest hazardous PM10 concentrations associated with Saharan dust storms but lower PM10 concentrations during the summer. The WRF dust simulations show a similar temporal pattern to the observations in Dakar, Senegal, with notable biases. However, the WRF model suggests that the highest dust concentrations are found across the northern half of Senegal during the winter season where there are no currently PM measurements. Health data during 2015-2016 show the highest prevalence of asthma and bronchitis in Dakar, Senegal, suggesting that other sources of air pollution are important. Acute respiratory infection is prevalent throughout the country with the high prevalence found in rural zones, for children between 12 and 59 months. All measures including real-time monitoring, air quality forecast, and communication should be used to protect the public from potentially hazardous environmental conditions during the winter season.


Aquaporin-1 antibody in neuromyelitis optical patients.
To find out the prevalence of aquaporin-antibody (Aqp-Ab) and characterize Aqp-Ab associated clinical features in NMO, Aqp-1 and Aqp-4-Abs were examined using radioimmunoprecipitation and cell-based assays, respectively. Aqp-4 and Aqp-1-Abs were detected in 20/30 and 8/30 NMO patients, respectively. One patient was Aqp-1-Ab single-positive, 13 patients were Aqp-4-Ab single-positive, 7 patients were Aqp-4/Aqp-1-Ab double-positive and 9 patients were seronegative. All double-positive patients had optic neuritis during the first attack. Only 2/29 MS patients and none of the control idiopathic intracranial hypertension patients were Aqp-1-Ab positive. Aqp-1-Ab is usually detected in Aqp-4-Ab positive NMO patients and might be involved in optic neuritis pathogenesis.


Transfer of radiation-induced spins from deoxyribonucleic and thymidylic acids to propyl gallate.
When calf thymus deoxyribonucleic acid (DNA), propyl gallate (PG) and their five molecular mixtures (with PG content of 1, 2, 5, 10 and 20%) are irradiated with gamma-rays in dry state in vacuum at 296 degrees K, the ESR spectra of all molecular mixtures differ strikingly from those of DNA, but bear a close resemblance to those of PG. The spin yield in the PG contained in these mixtures is two to three orders of magnitude higher than that in the case of PG irradiated separately. Furthermore, on the basis of the relative saturation characteristics of ESR spectra, these molecular mixtures behave more like PG than like DNA. It may be inferred that the radiation-induced spins could be transferred from DNA to PG. With r representing the molar ratio of nucleotides to PG, we have found a good linear correlation between the transfer ratio (TR) and square root of r. One PG molecule could protect at least 68 nucleotides in the duplex DNA chain, and thereby the minimal range of spin transfer is estimated at 115 A. Results obtained from irradiation at 77 degrees K show that PG exerts no protective effect on DNA, so DNA sustains an irreversible damage. It is thought that the spin transfer from DNA to PG is exclusively due to a hydrogen transfer mechanism. We have also demonstrated the transfer of radiation-induced spins from both thermally denatured DNA and TMP to PG. The former process can be ascribed primarily to the hydrogen transfer mechanism, whereas the latter, as in the case of native DNA, exclusively to this mechanism.


Distinctive clinical and neuroimaging characteristics of longitudinally extensive transverse myelitis associated with aquaporin-4 autoantibodies.
Longitudinally extensive transverse myelitis (LETM) is a characteristic feature of Neuromyelitis Optica (NMO), but it can also occur in several other inflammatory diseases of the central nervous system (CNS). An IgG autoantibody that binds to aquaporin-4 (AQP4), the predominant water channel of the CNS, is a reliable biomarker of the NMO spectrum disorders, and if detected predicts the recurrence of the myelitis. In this study, we compared the clinical and neuroimaging characteristics of AQP4-IgG+ and AQP4-IgG- LETM patients. Thirty-seven first-ever LETM patients were retrospectively evaluated and divided into two groups according to the presence of AQP4 autoantibodies. AQP4-IgG was detected in the serum and in the cerebrospinal fluid of sixteen patients. The female to male ratio was higher in AQP4-IgG+ patients. Intractable nausea and vomiting and paroxysmal tonic spasms often accompanied the LETM in AQP4-IgG+ patients. T2-weighted spinal cord MRI revealed that inflammatory lesions extending into the brainstem and involving the central grey matter occurred more frequently in AQP4-IgG+ LETM patients. Hypointense lesions on T1-weighted spinal cord MRI were detected more frequently in the seropositive group, and their presence correlated with attack severity. In conclusion, this study provides clinical and spinal cord neuroimaging clues that can help distinguishing AQP4-IgG+ LETM patients.


New mouse model for dengue virus vaccine testing.
Several dengue (DEN) virus vaccines are in development; however, the lack of a reliable small animal model in which to test them is a major obstacle. Because evidence suggests that interferon (IFN) is involved in the human anti-DEN virus response, we tested mice deficient in their IFN functions as potential models. Intraperitoneally administered mouse-adapted DEN 2 virus was uniformly lethal in AG129 mice (which lack alpha/beta IFN and gamma IFN receptor genes), regardless of age. Immunized mice were protected from virus challenge, and survival times increased following passive transfer of anti-DEN polyclonal antibody. These results demonstrate that AG129 mice are a promising small animal model for DEN virus vaccine trials.


Development of Consensus-Based Best Practice Guidelines for Postoperative Care Following Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis.
Delphi process with multiple iterative rounds using a nominal group technique. The aim of this study was to use expert opinion to achieve consensus on various aspects of postoperative care following posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). Significant variability exists in postoperative care following PSF for AIS, despite a relatively healthy patient population and continuously improving operative techniques. Current practice appears based either on lesser quality studies or the perpetuation of long-standing protocols. An expert panel composed of 26 pediatric spine surgeons was selected. Using the Delphi process and iterative rounds using a nominal group technique, participants in this panel were presented with a detailed literature review and asked to voice opinion collectively during three rounds of voting (one electronic and two face-to-face). Agreement >80% was considered consensus. Interventions without consensus were discussed and revised, if feasible. Consensus was reached to support 19 best practice guideline (BPG) measures for postoperative care addressing non-ICU admission, perioperative pain control, dietary management, physical therapy, postoperative radiographs, surgical bandage management, and indications for discharge. We present a consensus-based BPG consisting of 19 recommendations for the postoperative management of patients following PSF for AIS. This can serve to reduce variability in practice in this area, help develop hospital specific protocols, and guide future research. 5.


Hypertensive patients show delayed wound healing following total hip arthroplasty.
Prolonged wound-discharge following total hip arthroplasty (THA) is associated with an increased risk of infection. However, the potential role of hypertension in prolonging the duration of wound healing in this population has not yet been investigated. The aim of the present study was to compare healing in this population that has not yet been investigated. The aim of the present study was to compare hypertensive and normotensive THA patients in terms of the length of time required to achieve a dry wound and the length of stay in the hospital. One hundred and twenty primary THA patients were evaluated. Pre-operative clinical history and physical examination revealed that 29 were hypertensive and 91 were normotensive. The two groups were statistically matched using optimal propensity score matching. The outcomes of interest were the number of days until a dry wound was observed and the duration of hospital stay. The average systolic blood pressures were 150.1 mmHg and 120.3 mmHg for the hypertensive and normotensive groups, respectively. The mean number of days until the wound was dry was 3.79 for the hypertensive group and 2.03 for the normotensive group. Hypertensive patients required more days for their wounds to dry than normotensive patients (odds ratio = 1.65, p<0.05). No significant difference in the duration of hospital stay was found between the two groups. Hypertensive patients had a higher risk of prolonged wound discharge after THA than their normotensive counterparts. Patients with prolonged wound drainage are at greater risk for infection. Clinicians should pay particular attention to infection-prevention strategies in hypertensive THA patients.


Development and validation of prognostic survival models in newly diagnosed Parkinson's disease.
The objective of this study was to develop valid prognostic models to predict mortality, dependency, and "death or dependency" for use in newly diagnosed Parkinson's disease (PD). The models were developed in the Parkinsonism Incidence in North-East Scotland study (UK, 198 patients) and validated in the ParkWest study (Norway, 192 patients), cohorts that attempted to identify and follow-up all new PD cases in the study area. Dependency was defined using the Schwab & England scale. We selected variables measured at time of diagnosis to include in the models. Internal validation and external validation were performed by calculating C-statistics (discrimination) and plotting observed versus predicted risk in quantiles of predicted risk (calibration). Older age, male sex, increased severity of axial features, and Charlson comorbidity index were independent prognostic factors in the mortality model. Increasing age, higher smoking history, increased severity of axial features, and lower MMSE score were independent predictors in the models of dependency and "death or dependency." Each model had very good internal calibration and very good or good discrimination (internal and external C-statistics for the models were 0.73-0.75 and 0.68-0.78, respectively). Although each model clearly separated patients into groups according to risk, they tended to overestimate risk in ParkWest. The models were recalibrated to the baseline risk in the ParkWest study and then calibrated well in this cohort. We have developed prognostic models for predicting medium-term risk of important clinical outcomes in newly diagnosed PD. These models have validity for use for stratification of randomization, confounder adjustment, and case-mix correction, but they are inadequate for individualized prognostication. © 2017. The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.


Processing of antifouling paint particles by Mytilus edulis.
Particles of spent antifouling paint collected from a marine boatyard were ground and subsequently administered to the filter-feeding bivalve, Mytilus edulis, maintained in static aquaria. Concentrations of Cu and Zn were measured in seawater throughout a 16 h feeding phase and a 24 h depuration phase, in rejected and egested particles collected during the respective phases, and in the organisms themselves at the end of the experiments. Concentrations and distributions of Cu and Zn in processed particles indicated that M. edulis was able to ingest paint particles, regardless of whether nutritionally viable silt was present, and no mechanism of particle discrimination was evident. Enrichment of Cu and Zn in the visceral mass of individuals and in the aqueous phase during depuration supported these assertions, although elevated concentrations in other compartments of the organism (e.g. shell, gill) suggested that biotic and abiotic uptake of aqueous metal was also important.


The diagnostic accuracy of attention-deficit/hyperactivity disorder in adults with substance use disorders.
Adult attention deficit/hyperactivity disorder (ADHD) is a common comorbid condition to substance use disorder (SUD) and is associated with worse prognosis and quality of life. This review summarizes recent work assessing ADHD diagnosis reliability in SUD patients and provides arguments to enhance the accuracy of detecting this disorder. Adequate diagnosis of ADHD in SUD patients is challenged by phenomenological aspects of addiction and frequently associated other psychiatric disorders that overlap with key symptoms of ADHD. A detailed comprehensive search for child and adult symptoms including the temporal relationship of ADHD, substance use and other psychiatric disorders should maximize the validity and the reliability of adult ADHD diagnosis in this population. Further, a follow-up evaluation of ADHD symptoms during treatment of SUD may reduce the likelihood of misdiagnosis. Considering the high rate of ADHD comorbidity among SUD patients, it is crucial to promote a systematic diagnostic approach to this disorder in specialized addiction treatment settings. However, overlapping symptoms between disorders frequently challenge the accuracy of adult ADHD diagnosis. Areas in need of further investigations include the development of valid screening procedures, associated neuropsychological factors and effective treatment strategies for these populations.


Short article: Mortality and differential diagnoses of villous atrophy without coeliac antibodies.
Villous atrophy (VA) of the small bowel is mainly related to coeliac disease (CD), whose diagnosis is made on the basis of positive endomysial/tissue transglutaminase antibodies while on a gluten-containing diet in the vast majority of patients. However, VA can also occur in other conditions whose epidemiology is little known. Our aim was to study the epidemiology and clinical features of these rare enteropathies. Clinical and laboratory data of all the patients with VA directly diagnosed in our centre in the last 15 years were collected and statistically analysed. Between September 1999 and June 2015, 274 patients were diagnosed with VA. A total of 260 patients were also positive to coeliac antibodies; the other 14 had VA, but no IgA endomysial antibodies: five had common variable immunodeficiency, three had dermatitis herpetiformis, two had IgA deficiency associated with CD, one had abdominal lymphoma, one had unclassified sprue, one had olmesartan-associated enteropathy and one had seronegative CD. Mortality was 6.0 deaths per 100 person years (95% confidence interval: 2.2-16) in patients with VA but negative coeliac antibodies, whereas only 0.2 deaths per 100 person years (95% confidence interval: 0.1-0.6) occurred in coeliac patients. Patients with VA and negative endomysial antibodies are rare. However, these forms of VA identify specific causes that can be diagnosed. These patients are affected by a very high mortality.


[Hand hygiene: health professionals' knowledge and areas for improvement].
The objective of this study was to analyze knowledge on hand hygiene among staff workers in the Andalusian Public Health System (Spain). This was a cross-sectional study with surveys (2011) using the Hand Hygiene Knowledge Assessment Questionnaire for Healthcare Workers with the latent class analysis technique. The average number of questions answered correctly was 17.51±3.68. Questions with lower percentages of correct responses were those on hand hygiene for prevention of microorganism transmission to patients and those on hand- rubbing versus hand-washing. We obtained a model with 7 latent classes. Workers with lower knowledge tended to be younger, males, and non-healthcare workers. Having received previous training did not necessarily ensure excellent knowledge. The study concludes that hand hygiene training programs need to be revised in order to improve knowledge on conceptual characteristics involved in the transmission of microorganisms via the hands.


Visual snow syndrome: a comparison between an Italian and British population.
Visual snow manifests as a pan-field, dynamic visual disturbance described as continuous television static-like tiny flickering dots. Current diagnostic criteria further require at least two additional symptoms for visual snow syndrome (VSS) from: palinopsia (afterimages and trailing); entoptic phenomena (floaters, blue field entoptic phenomenon, photopsia, self-light of the eye); photophobia and nyctalopia. Our objective was to compare the phenotype of VSS in an Italian and British population. Patients with VSS were characterized clinically using the current criteria. An online survey was prepared in collaboration with the patient group Eye-on-Vision. Patients were directed to the site if they contacted us by email asking to be involved in research. After data collection, we compared the phenotypic characteristics of a subgroup of British versus Italian patients taking part in the survey. As we expected more responses from the UK, we matched 100 UK patients for gender and age with our Italian cohort. Patients were enrolled from the UK (n = 100) and Italy (n = 100). The populations had similar demography. After multiple correction testing there were no differences in VSS features between the two groups. The same was true for the prevalence of migraine and previous use of recreational drugs. This is the first study comparing the phenotype of VSS between two distinct populations. Our findings suggest that the visual snow phenotype, as well as migraine comorbidity, is similar across the two groups.


Screening of selected pesticides for oestrogen receptor activation in vitro.
Twenty pesticides were tested for their ability to activate the oestrogen receptor in vitro using an MCF7 cell proliferation assay and a Yeast Oestrogen Screen. The fungicides fenarimol, triadimefon, and triadimenol were identified as weak oestrogen receptor agonists, which at 10 microM induces a 2.0, 2.4, and 1.9-fold increase in proliferation of human MCF7 breast cancer cells (E3 clone). The relative proliferation efficiency (RPE) was 43-69%, indicating partial agonism at the oestrogen receptor. Several pesticides did not have any effect on the proliferation response after 6 days of exposure, including: chlorpyrifos, diuron, iprodion, linuron, pentachlorphenol, prochloraz, propioconazol, propyzamine, quintozen, tetrachorvinphos and tetradifon. Some pesticides resulted in a negligible proliferation response, which was not statistically significant under the present experimental conditions. These were: bromopropylate, chlorfenvinphos, chlorobenzilate, dicofol, heptachlor, and imazalil. Fenarimol and dicofol also gave rise to a positive oestrogenic response in yeast cells transfected with the oestrogen receptor alpha, whereas the remaining compounds resulted in a negative response due either to biological inactivity or cytotoxocity to the yeast cells. The EC50 for fenarimol was estimated to be 13 microM in the yeast cells, compared with an EC50 of 3 microM in the MCF7 cells, indicating higher sensitivity of the latter assay. No in vivo data for fenarimol, triadimefon or triadimenol have previously been published that support oestrogenic activity in the intact animal. Thus, from the present results we suggest that oestrogen receptor activation may not be an important mode of action for these compounds. The need to include at least two bioassays in a screening procedure and for combining in vitro and in vivo data is emphasized.


Are recently deglaciated areas at both poles colonised by the same bacteria?
Polar glacier forefields offer an unprecedented framework for studying community assembly processes in regions that are geographically and climatically isolated. Through amplicon sequence variant (ASV) inference, we compared the composition and structure of soil bacterial communities from glacier forefields in Iceland and Antarctica to assess overlap between communities and the impact of established cryptogamic covers on the uniqueness of their taxa. These pioneer microbial communities were found to share only 8% of ASVs and each taxonomic group's contribution to the shared ASV data subset was heterogeneous and independent of their relative abundance. Although the presence of ASVs specific to one glacier forefield and/or different cryptogam cover values confirms the existence of habitat specialist bacteria, our data show that the influence of cryptogams on the edaphic bacterial community structure also varied also depending on the taxonomic group. Hence, the establishment of distinct cryptogamic covers is probably not the only factor driving the uniqueness of bacterial communities at both poles. The structure of bacterial communities colonising deglaciated areas seems also conditioned by lineage-specific limitations in their dispersal capacity and/or their establishment and persistence in these isolated and hostile regions.