Genetic and quantitative assessment of Vibrio vulnificus populations in oyster (Crassostrea virginica) tissues.
Vibrio vulnificus is a leading cause of shellfish-associated food-borne illness. US regulations stipulate shellfish processing procedures to limit V. vulnificus densities; however, the effect of these procedures on V. vulnificus strain distribution and/or genetic diversity is unknown. Vibrio vulnificus concentrations and strain diversity were analysed in various oyster tissues stored overnight at 26°C that were subsequently divided into two treatment groups: one received post-harvest processing (PHP) via individual quick freeze and one was stored on ice. Vibrio vulnificus densities were 10-fold lower in all PHP-treated tissues compared with untreated tissues. Genetic diversity of V. vulnificus was assessed by BOX-PCR genotyping and was high in all oyster tissues, but was significantly lower in untreated compared with PHP-treated oysters. BOX-PCR discriminated strains into BOX-C (clinical-associated) and BOX-E (environmental-associated) types based on a 1.1 kb DNA band, which correlated well (83% agreement) with 16S rRNA (A/B) typing. A significantly higher proportion of BOX-C isolates were recovered from PHP oysters compared with untreated oysters (24% of all isolates versus 12%) suggesting that BOX-C strains may be more resistant to treatment. These results reveal highly diverse populations of V. vulnificus in oysters with different responses to PHP, emphasizing the need to better understand the organism's ecology and population genetics to optimize food safety practices.


The influence of different versions of FLUKA and GEANT4 on the calculation of response functions of ionization chambers in clinical proton beams.
Objective.To investigate the influence of different versions of the Monte Carlo codesgeant4 andflukaon the calculation of overall response functionsfQof air-filled ionization chambers in clinical proton beams.Approach. fQfactors were calculated for six plane-parallel and four cylindrical ionization chambers withgeant4 andfluka. These factors were compared to already published values that were derived using older versions of these codes.Main results.Differences infQfactors calculated with different versions of the same Monte Carlo code can be up to ∼1%. Especially forgeant4, the updated version leads to a more pronounced dependence offQon proton energy and to smallerfQfactors for high energies.Significance.Different versions of the same Monte Carlo code can lead to differences in the calculation offQfactors of up to ∼1% without changing the simulation setup, transport parameters, ionization chamber geometry modeling, or employed physics lists. These findings support the statement that the dominant contributor to the overall uncertainty of Monte Carlo calculatedfQfactors are type-B uncertainties.


Ultrastructure of picosecond laser intrastromal photodisruption.
To investigate the ultrastructure of the corneal stroma after picosecond intrastromal photodisruption with a neodymium-doped yttrium-lithium-fluoride (Nd:YLF) laser. We performed picosecond intrastromal photodisruption on six human eye-bank eyes using a lamellar technique. Thirty picosecond pulses at 1000 Hz and 20 to 25 mJ per pulse were placed in an expanding spiral pattern, the pulses separated by 15 microns. Three layers were placed in the anterior stroma, separated from each other by 15 microns. In addition, intrastromal radial and arcuate incisions were generated in two living rabbit eyes in a plane perpendicular to the corneal surface. After the procedure, the corneas were processed for scanning and transmission electron microscopy. Scanning electron microscopy of the eye-bank eyes demonstrated multiple, coalescing intrastromal cavities forming a layer oriented parallel to the corneal surface. These cavities had smooth inner walls. Transmission electron microscopy demonstrated tissue loss surrounding some cavities, with the terminated ends of collagen fibrils clearly evident. Other cavities were formed by separation of lamellae, with little evidence of tissue loss. A pseudomembrane was present along the margin of some cavities. Although there was occasional underlying tissue disruption along the border of a cavity, there was no evidence of thermal damage or tissue necrosis. The perpendicular photodisruptions demonstrated intrastromal cleavage of corneal collagen similar to diamond-knife incisions, with the exception of intact overlying Bowman's and epithelial layers. Intrastromal photodisruption with a Nd:YLF picosecond laser induced no thermal necrosis or coagulative change in the region of tissue interaction. Lamellar intrastromal photodisruption demonstrated both tissue loss and lamellar separation when performed with the current treatment parameters, possibly limiting ablation efficiency and predictability.


Caveolin mediates rapid glucocorticoid effects and couples glucocorticoid action to the antiproliferative program.
Many glucocorticoid (Gc) actions are of rapid onset and therefore require acute regulation of intracellular signaling cascades. Integration of diverse extracellular signals requires cross-talk between intracellular pathways, suggesting the existence of nodes for signal interaction, such as the specialized membrane microdomains caveolae. We have identified rapid Gc-dependent phosphorylation of caveolin, and protein kinase B (PKB)/Akt, in the lung epithelial cell line A549 and found this was dependent on src kinases. There was also activation of PKB downstream molecules glycogen synthase kinase-3beta, and mammalian target of rapamycin. Subcellular fractionation colocalized glucocorticoid receptor (GR) and c-src to caveolin-containing membrane fractions. Coimmunoprecipitation studies also identified interactions between GR and caveolin and suggested that the activation function 1 domain within the GR may serve to support an interaction between GR and caveolin. Disruption of lipid raft formation, impairment of caveolin function using dominant-negative caveolin, down-regulation of caveolin-1 using short hairpin RNA or complete ablation of caveolin-1 prevented Gc-induced activation of PKB. Loss of caveolin-1 also prevents Gc activation of glycogen synthase kinase-3beta and mammalian target of rapamycin. In contrast, caveolin interference/down-regulation had no effect on Gc transactivation. Functional analysis of caveolin-1 knockdown and knockout cells identified profound loss of Gc-mediated growth inhibition compared with controls, with a requirement for caveolin in order for Gc to regulate cell cycle progression. Therefore, disruption of caveolae leads to dissociation of Gc action, with impaired induction of PKB activation, and cell growth inhibition, but with negligible effects on Gc transactivation. These observations have implications for understanding the diverse physiological actions of Gc.


The separate and combined effects of nicotine and alcohol on working memory capacity in nonabstinent smokers.
Research indicates that nicotine and alcohol are often used on the same occasion. However, the reasons for their concurrent use are not well understood. We hypothesized that one reason smokers use tobacco when they drink alcohol is to compensate for alcohol's negative effects on processing capacity with nicotine's enhancement of processing capacity. As such, the present study tested this theory by using an independent groups design to examine the separate and combined acute effects of alcohol and nicotine on working memory (WM) capacity. Nonabstinent daily smokers (n = 127) performed the counting span task (CSPAN) after consuming either an alcohol (men: 0.8 g/kg; women: 0.7 g/kg) or placebo beverage and smoking either nicotinized (1.14 mg nicotine, 15.9 mg tar) or denicotinized (.06 mg nicotine, 17.9 mg tar) cigarettes. Analyses revealed that smokers who smoked the nicotinized cigarettes performed significantly worse on the CSPAN task than smokers who smoked the denicotinized cigarettes. Although there was no main effect of alcohol on WM performance, women exhibited better WM performance than men after consuming alcohol whereas men performed better than women on the WM task after consuming the placebo beverage. Findings also revealed no interaction between the two substances on WM performance. Taken together, results suggest that nicotine impairs nonabstinent smokers' verbal WM capacity and that gender moderates the effects of alcohol on WM. Furthermore, the present findings failed to support the notion that nicotine compensates for alcohol-related decrements in working memory capacity.


Amplicon Sequencing as a Potential Surveillance Tool for Complexity of Infection and Drug Resistance Markers in Plasmodium falciparum Asymptomatic Infections.
Genotyping Plasmodium falciparum subpopulations in malaria infections is an important aspect of malaria molecular epidemiology to understand within-host diversity and the frequency of drug resistance markers. We characterized P. falciparum genetic diversity in asymptomatic infections and subsequent first febrile infections using amplicon sequencing (AmpSeq) of ama1 in Coastal Kenya. We also examined temporal changes in haplotype frequencies of mdr1, a drug-resistant marker. We found >60% of the infections were polyclonal (complexity of infection [COI] >1) and there was a reduction in COI over time. Asymptomatic infections had a significantly higher mean COI than febrile infections based on ama1 sequences (2.7 [95% confidence interval {CI}, 2.65-2.77] vs 2.22 [95% CI, 2.17-2.29], respectively). Moreover, an analysis of 30 paired asymptomatic and first febrile infections revealed that many first febrile infections (91%) were due to the presence of new ama1 haplotypes. The mdr1-YY haplotype, associated with chloroquine and amodiaquine resistance, decreased over time, while the NY (wild type) and the NF (modulates response to lumefantrine) haplotypes increased. This study emphasizes the utility of AmpSeq in characterizing parasite diversity as it can determine relative proportions of clones and detect minority clones. The usefulness of AmpSeq in antimalarial drug resistance surveillance is also highlighted.


Establishment of the International Assessment Committee of Bone and Joint Diseases.
During the International Conference of the Bone and Joint Decade, held in Tokyo in April 2002, the International Assessment Committee of Bone and Joint Diseases was established. This committee is responsible for data collection, effective prevention and treatment, supply of care provisions, costs and priorities, and measurement to determine the outcome of patients with bone and joint diseases. Study planning was initiated by the Japanese Committee of Assessment, in cooperation with the Bone and Joint Monitor Project conducted by Prof. Anthony Woolf. As a result of our studies, we expect to obtain data concerning international comparisons of incidence, prevalence, and impact, as well as secular trends regarding the burden of musculoskeletal conditions, risk factors, and outcomes of each condition. Described here are results of population-based studies regarding the prevalence of rheumatoid arthritis (RA), osteoarthritis, osteoporosis, and limb fractures in Japan compared with those in Western countries, as well as a comparison of secular trends of RA incidence between Japanese and European subjects.


Health beliefs, practice, and priorities for health care of Arab Muslims in the United States.
The Arab Muslim population is one of the dramatically increasing minorities in the United States. In addition to other factors, religion and cultural background influence individuals' beliefs, behaviors, and attitudes toward health and illness. The author describes health beliefs and practices of the Arab Muslim population in the United States. That population is at an increased risk for several diseases and faces many barriers to accessing the American health care system. Some barriers, such as modesty, gender preference in healthcare providers, and illness causation misconceptions, arise out of their cultural beliefs and practices. Other barriers are related to the complexity of the health care system and the lack of culturally competent services within it. Nurses need to be aware of these religious and cultural factors to provide culturally competent health promotion services for this population. Nurses also need to integrate Islamic teachings into their interventions to provide appropriate care and to motivate healthy behaviors.


Ultrasound-Enhancing Agent Safely Enhances Left Ventricular Visualization by Transthoracic Echocardiography in Patients on ECMO Support.
The authors investigated if the use of ultrasound-enhancing agents (UEA) can safely improve left ventricular (LV) image quality by transthoracic echocardiography (TTE) in patients on extracorporeal membrane oxygenation (ECMO). This study was performed in a tertiary cardiothoracic and ECMO center in London, United Kingdom. The authors included 18 prospectively identified consecutive patients requiring TEE supported on peripherally implanted ECMO. TTE was performed before and after the UEA administration. The authors assessed the LV image quality using the biplane (apical-4-chamber and apical-2-chamber views) endocardial border definition index (1 = good, 2 = suboptimal, 3 = poor, and 4 = unavailable), as well as the feasibility of LV ejection fraction (LVEF) measurement. The authors also gathered sequential clinical information for the next 24 hours. The patients' median age was 47 years (35, 65), and 5 (28%) were women. The biplane endocardial border definition index improved from the suboptimal to the good range (2.167 [1.812, 3.042] v 1.500 [1.417, 1.792], p = 0.0004) after the use of UEA. The feasibility of LVEF tripled from 25% (n = 5) to 83% (n = 15) (p = 0.0008) with UEA use. The UEA did not set off the bubble alarm and did not impact clinical or ECMO parameters. The use of UEA significantly improved the quality of LV biplane images by transthoracic echocardiography, transforming them from suboptimal to good in patients supported with peripherally implanted ECMO. UEA use tripled the feasibility of measuring LVEF by TTE without affecting clinical and ECMO parameters.


Efficacy of piperacillin in combination with novel β-lactamase inhibitor IID572 against β-lactamase-producing strains of Enterobacteriaceae and Staphylococcus aureus in murine neutropenic thigh infection models.
The neutropenic murine thigh infection model was used to assess the effectiveness of IID572, a novel β-lactamase inhibitor, in rescuing piperacillin activity against bacterial strains expressing various β-lactamase enzymes. Mice (n = 4/group) were inoculated with Enterobacteriaceae or Staphylococcus aureus bacterial strains expressing a range of β-lactamases via intramuscular injection. Two hours after bacterial inoculation, subcutaneous treatment with piperacillin/IID572 or piperacillin/tazobactam every 3 h was initiated. Animals were euthanized via CO2 24 h after the start of therapy and bacterial cfu (log10 cfu) per thigh was determined, and the static dose was calculated. In a dose-dependent manner, piperacillin/IID572 reduced the thigh bacterial burden in models established with Enterobacteriaceae producing class A, C and D β-lactamases (e.g. ESBLs, KPC, CMY-2 and OXA-48). Piperacillin/IID572 was also efficacious against MSSA strains, including one producing β-lactamase. Static doses of piperacillin/IID572 were calculable from animals infected with all strains tested and the calculated static doses ranged from 195 to 4612 mg/kg/day piperacillin, the active component in the combination. Of the 13 strains investigated, a 1 log10 bacterial reduction was achieved for 9 isolates and a 2 log10 reduction was achieved for 3 isolates; piperacillin/tazobactam was not efficacious against 6 of the 13 isolates tested. In contrast to tazobactam, IID572 was able to rescue piperacillin efficacy in murine thigh infection models established with β-lactamase-producing strains of Enterobacteriaceae and S. aureus, including those expressing ESBLs or serine carbapenemases.


Subclinical right ventricular dysfunction in patients with asymptomatic type 2 diabetes mellitus: A cross-sectional study.
Diabetic cardiomyopathy, which involves both the right and left ventricles, progresses from a preclinical stage to overt heart failure. Detection of this entity at a preclinical stage could be crucial in intervening to halt its progression to overt heart failure. There is a paucity of literature on subclinical RV dysfunction in diabetic patients, and it is even rarer in the Indian literature. Our study intended to study this clinical entity through an echocardiographic assessment of asymptomatic patients. This was a cross-sectional observational analytic study, comparing subclinical RV dysfunction in diabetic and non-diabetic subjects by using echocardiography as a primary objective, while the secondary objective of the study was to find out the correlation between RV dysfunction and the duration of diabetes mellitus and HbA1C levels. Conventional echocardiography with tissue Doppler imaging (TDI) was used to measure nine different echocardiographic parameters in the diabetic and non-diabetic groups. All probable causes of RV dysfunction were excluded before enrolling the patients in the study. Unpaired t-test was used to compare the parameters between the two groups, and multivariate regression analysis was done taking into consideration age, duration of diabetes, and HbA1C levels as the independent variables, and echocardiographic parameters as the dependent variables. Out of the nine different echocardiographic parameters, Tricuspid annular plane systolic excursion (TAPSE), RV end diastolic diameter (RVEDD), Tricuspid peak late diastolic velocity (A), E/A ratio, RV basal segment peak myocardial systolic velocity (Sm), RV basal segment peak early diastolic velocity (Em), RV basal segment peak late diastolic velocity (Am), and E/Em ratio showed statistically significant differences between the two groups. These results show the presence of subclinical RV dysfunction in diabetic patients. TAPSE and E/A ratio showed a significant correlation with the duration of diabetes, while Em showed a significant correlation with HbA1C. Diabetes mellitus is associated with subclinical systolic as well as diastolic RV dysfunction. In addition to helping identify people at high risk, the early recognition of RV dysfunction gives us a window of opportunity to take action and slow down the disease's course. This study emphasizes that the early identification of RV diastolic as well as systolic dysfunction in asymptomatic Type 2 diabetic patients can be a helpful tool in halting the progression of disease from subclinical to frank clinical cases, thereby preventing the morbidity and mortality associated with heart failure. Hence, it adds value to the pre-existing literature.


Current and emerging therapies for the treatment of myasthenia gravis.
Myasthenia gravis (MG) is an autoimmmune disease in which autoantibodies to different antigens of the neuromuscular junction cause the typical weakness and fatigability. Treatment includes anticholinesterase drugs, immunosuppression, immunomodulation, and thymectomy. The autoimmune response is maintained under control by corticosteroids frequently associated with immunosuppressive drugs, with improvement in the majority of patients. In case of acute exacerbations with bulbar symptoms or repeated relapses, modulation of autoantibody activity by plasmapheresis or intravenous immunoglobulins provides rapid improvement. Recently, techniques removing only circulating immunoglobulins have been developed for the chronic management of treatment-resistant patients. The rationale for thymectomy relies on the central role of the thymus. Despite the lack of controlled studies, thymectomy is recommended as an option to improve the clinical outcome or promote complete remission. New videothoracoscopic techniques have been developed to offer the maximal surgical approach with the minimal invasiveness and hence patient tolerability. The use of biological drugs such as anti-CD20 antibodies is still limited but promising. Studies performed in the animal model of MG demonstrated that several more selective or antigen-specific approaches, ranging from mucosal tolerization to inhibition of complement activity or cellular therapy, might be feasible. Investigation of the transfer of these therapeutic approaches to the human disease will be the challenge for the future.


Chronic imaging of cortical sensory map dynamics using a genetically encoded calcium indicator.
In vivo optical imaging can reveal the dynamics of large-scale cortical activity, but methods for chronic recording are limited. Here we present a technique for long-term investigation of cortical map dynamics using wide-field ratiometric fluorescence imaging of the genetically encoded calcium indicator (GECI) Yellow Cameleon 3.60. We find that wide-field GECI signals report sensory-evoked activity in anaesthetized mouse somatosensory cortex with high sensitivity and spatiotemporal precision, and furthermore, can be measured repeatedly in separate imaging sessions over multiple weeks. This method opens new possibilities for the longitudinal study of stability and plasticity of cortical sensory representations.


Ultrastructural alterations of motor cortex synaptic junctions in Brown Swiss cattle with weaver syndrome.
An ultrastructural comparison was made between the motor cortex synapses of the brain of 4 adult Brown Swiss cattle with weaver syndrome and 2 healthy cattle (a Holstein steer and a Guernsey cow). Compared with the healthy cattle, the paramembranous densities at synaptic junctions of cattle with weaver syndrome had a decreased mean height of the presynaptic dense projections (P less than 0.001), had significantly smaller peak-to-peak distances (P less than 0.001), and had a significantly decreased mean thickness of the postsynaptic density (P less than 0.0001). These synaptic changes in cattle with weaver syndrome may be associated with clinical manifestations of the syndrome, such as impairment of transmitter release, instability of postsynaptic receptor sites, lesion-induced synaptic turnover from injury elsewhere in the CNS, or loss of a specific cell population of the motor cortex.


Size-dependent patterns of cell proliferation and migration in freely-expanding epithelia.
The coordination of cell proliferation and migration in growing tissues is crucial in development and regeneration but remains poorly understood. Here, we find that, while expanding with an edge speed independent of initial conditions, millimeter-scale epithelial monolayers exhibit internal patterns of proliferation and migration that depend not on the current but on the initial tissue size, indicating memory effects. Specifically, the core of large tissues becomes very dense, almost quiescent, and ceases cell-cycle progression. In contrast, initially-smaller tissues develop a local minimum of cell density and a tissue-spanning vortex. To explain vortex formation, we propose an active polar fluid model with a feedback between cell polarization and tissue flow. Taken together, our findings suggest that expanding epithelia decouple their internal and edge regions, which enables robust expansion dynamics despite the presence of size- and history-dependent patterns in the tissue interior.


Comparative genomics of mammalian hibernators using gene networks.
In recent years, the study of the molecular processes involved in mammalian hibernation has shifted from investigating a few carefully selected candidate genes to large-scale analysis of differential gene expression. The availability of high-throughput data provides an unprecedented opportunity to ask whether phylogenetically distant species show similar mechanisms of genetic control, and how these relate to particular genes and pathways involved in the hibernation phenotype. In order to address these questions, we compare 11 datasets of differentially expressed (DE) genes from two ground squirrel species, one bat species, and the American black bear, as well as a list of genes extracted from the literature that previously have been correlated with the drastic physiological changes associated with hibernation. We identify several genes that are DE in different species, indicating either ancestral adaptations or evolutionary convergence. When we use a network approach to expand the original datasets of DE genes to large gene networks using available interactome data, a higher agreement between datasets is achieved. This indicates that the same key pathways are important for activating and maintaining the hibernation phenotype. Functional-term-enrichment analysis identifies several important metabolic and mitochondrial processes that are critical for hibernation, such as fatty acid beta-oxidation and mitochondrial transport. We do not detect any enrichment of positive selection signatures in the coding sequences of genes from the networks of hibernation-associated genes, supporting the hypothesis that the genetic processes shaping the hibernation phenotype are driven primarily by changes in gene regulation.


Relationship of DAT1 and adult ADHD to task-positive and task-negative working memory networks.
Alterations in working memory, default-mode network (DMN), and dopamine transporter have all been proposed as endophenotypes for attention-deficit/hyperactivity disorder (ADHD). Despite evidence that these systems are interrelated, their relationship to each other has never been studied in the context of ADHD. In order to understand the potential mediating effects of task-positive and task-negative networks between DAT1 and diagnosis, we tested effects of genotype and diagnosis on regions of positive and negative BOLD signal change (as measured with fMRI) in 53 adults with ADHD and 38 control subjects during a working memory task. We also examined the relationship of these responses to ADHD symptoms. Our results yielded four principal findings: 1) association of the DAT1 9R allele with adult ADHD, 2) marginal DAT1 association with task-related suppression in left medial PFC, 3) marginal genotype×diagnosis interaction in the dorsal anterior cingulate cortex, and 4) correlation of DMN suppression to ADHD symptoms. These findings replicate the association of the 9R allele with adult ADHD. Further, we show that DMN suppression is likely linked to DAT1 and to severity of inattention in ADHD. DMN may therefore be a target of DAT1 effects, and lie on the path between the gene and inattention in ADHD.


Stigma: The Perspective of Workers on Community Mental Health Services-Brazil.
In this study, we have surveyed how professionals from multidisciplinary teams at psychosocial care centers (CAPS), in the city of São Paulo, understand the concept of mental illness stigma. The aim of the survey was to characterize the actions developed by the team to overcome stigma and, thus, contribute to develop strategies that incorporate overcoming stigma in the territory. Our objective is to get acquainted to the concepts about stigma shared by the participants. This survey was based on the theory of stigma by Erving Goffman; data were collected through semi-structured interviews with mental health professionals belonging to the CAPS teams. Results indicate that social exclusion is understood as a synonym to stigma, and that proximity of CAPS to society in the territory facilitates social inclusion and the overcoming of the mental illness stigma.


Regional recurrence in breast cancer patients with sentinel node micrometastases and isolated tumor cells.
The impact of axillary treatment in daily practice on 5-year regional recurrence rate in breast cancer patients with isolated tumor cells or micrometastases in the sentinel node (SLN). Axillary dissection is recommended in patients with tumor-positive SLNs. But, in recent studies, regional recurrence rates seemed low if dissection was omitted. We identified all patients in The Netherlands with invasive breast cancer who had an SLN biopsy before 2006, favorable primary tumor characteristics, and node-negative disease, isolated tumor cells or micrometastases as final nodal status. The primary endpoint was regional recurrence rate. To investigate differences in recurrence rates between patients with and without axillary treatment, a proportional hazard regression was carried out correcting for potential confounders. In total, 857 patients with node-negative disease, 795 patients with isolated tumor cells, and 1028 patients with micrometastases in the SLN were included. Without axillary treatment, the 5-year regional recurrence rates were 2.3%, 2.0%, and 5.6%, respectively. Compared with patients who underwent axillary treatment, the adjusted hazard ratio for regional recurrence in patients who underwent an SLN procedure only was 1.08 (95% CI, 0.23-4.98) for node-negative disease, 2.39 (95% CI, 0.67-8.48) for isolated tumor cells, and 4.39 (95% CI, 1.46-13.24) for micrometastases. Doubling of tumor size, grade 3 and negative hormone receptor status were also significantly associated with recurrence. Not performing axillary treatment in patients with SLN micrometastases is associated with an increased 5-year regional recurrence rate. Axillary treatment is recommended in patients with SLN micrometastases and unfavorable tumor characteristics.


What Executive Function Network is that? An Image-Based Meta-Analysis of Network Labels.
The current state of label conventions used to describe brain networks related to executive functions is highly inconsistent, leading to confusion among researchers regarding network labels. Visually similar networks are referred to by different labels, yet these same labels are used to distinguish networks within studies. We performed a literature review of fMRI studies and identified nine frequently-used labels that are used to describe topographically or functionally similar neural networks: central executive network (CEN), cognitive control network (CCN), dorsal attention network (DAN), executive control network (ECN), executive network (EN), frontoparietal network (FPN), working memory network (WMN), task positive network (TPN), and ventral attention network (VAN). Our aim was to meta-analytically determine consistency of network topography within and across these labels. We hypothesized finding considerable overlap in the spatial topography among the neural networks associated with these labels. An image-based meta-analysis was performed on 158 group-level statistical maps (SPMs) received from authors of 69 papers listed on PubMed. Our results indicated that there was very little consistency in the SPMs labeled with a given network name. We identified four clusters of SPMs representing four spatially distinct executive function networks. We provide recommendations regarding label nomenclature and propose that authors looking to assign labels to executive function networks adopt this template set for labeling networks.


Hearing screening for school children: comparison of low-cost, computer-based and conventional audiometry.
There is a need to develop affordable but effective audiometric screening equipment, particularly for use in low-income countries. With advances in computer technology, low-cost computer-based audiometer software has been developed. However, the efficacy of computer-based audiometers in hearing screening and diagnostic assessment requires investigation. The purpose of this study was to evaluate the accuracy of a low-cost, computer-based audiometric system in a school-based hearing screening programme. Eighty children were screened using the computer-based audiometer and with a conventional pure tone screening audiometer. Overall refer rates, as well as frequency and age effects on the accuracy of the computer-based audiometer, were considered. There was a significant relationship between the low-cost, computer-based audiometer and a conventional pure tone audiometer when a 40 dBHL refer criterion was used in school hearing screening and when test results at 500 Hz were excluded from analysis. However, background noise effects and software limitations in the computer-based system had major adverse effects on screening performance. The study results and preliminary practical experience with the system suggest that, with further software and hardware improvements, a low-cost, computer-based system may well be feasible for routine school screening in developing countries.


End-to-end memory-efficient reconstruction for cone beam CT.
Cone beam computed tomography (CBCT) plays an important role in many medical fields nowadays. Unfortunately, the potential of this imaging modality is hampered by lower image quality compared to the conventional CT, and producing accurate reconstructions remains challenging. A lot of recent research has been directed towards reconstruction methods relying on deep learning, which have shown great promise for various imaging modalities. However, practical application of deep learning to CBCT reconstruction is complicated by several issues, such as exceedingly high memory costs of deep learning methods when working with fully 3D data. Additionally, deep learning methods proposed in the literature are often trained and evaluated only on data from a specific region of interest, thus raising concerns about possible lack of generalization to other regions. In this work, we aim to address these limitations and propose LIRE: a learned invertible primal-dual iterative scheme for CBCT reconstruction. LIRE is a learned invertible primal-dual iterative scheme for CBCT reconstruction, wherein we employ a U-Net architecture in each primal block and a residual convolutional neural network (CNN) architecture in each dual block. Memory requirements of the network are substantially reduced while preserving its expressive power through a combination of invertible residual primal-dual blocks and patch-wise computations inside each of the blocks during both forward and backward pass. These techniques enable us to train on data with isotropic 2 mm voxel spacing, clinically-relevant projection count and detector panel resolution on current hardware with 24 GB video random access memory (VRAM). Two LIRE models for small and for large field-of-view (FoV) setting were trained and validated on a set of 260 + 22 thorax CT scans and tested using a set of 142 thorax CT scans plus an out-of-distribution dataset of 79 head and neck CT scans. For both settings, our method surpasses the classical methods and the deep learning baselines on both test sets. On the thorax CT set, our method achieves peak signal-to-noise ratio (PSNR) of 33.84 ± 2.28 for the small FoV setting and 35.14 ± 2.69 for the large FoV setting; U-Net baseline achieves PSNR of 33.08 ± 1.75 and 34.29 ± 2.71 respectively. On the head and neck CT set, our method achieves PSNR of 39.35 ± 1.75 for the small FoV setting and 41.21 ± 1.41 for the large FoV setting; U-Net baseline achieves PSNR of 33.08 ± 1.75 and 34.29 ± 2.71 respectively. Additionally, we demonstrate that LIRE can be finetuned to reconstruct high-resolution CBCT data with the same geometry but 1 mm voxel spacing and higher detector panel resolution, where it outperforms the U-Net baseline as well. Learned invertible primal-dual schemes with additional memory optimizations can be trained to reconstruct CBCT volumes directly from the projection data with clinically-relevant geometry and resolution. Such methods can offer better reconstruction quality and generalization compared to classical deep learning baselines.


Growth impairment in children with extrahepatic portal vein obstruction is improved by mesenterico-left portal vein bypass.
Extrahepatic portal vein obstruction (EHPVO) has been associated with growth impairment in children. We hypothesized that growth parameters improve after reversal of portal hypertension and restoration of mesenteric venous blood flow to the liver by the mesenterico-left portal vein bypass (MLPVB). A retrospective review of 45 children with idiopathic EHPVO who underwent MLPVB between 1997 and 2007 and had follow-up data for analysis was carried out. Growth was assessed using SD scores (z scores) for height, weight, and body mass index (BMI) at the time of operation and at early (5-12 months) and late (13-24 months) follow-up. The mean height and weight of children with EHPVO was significantly lower than the general population before surgery. Mean BMI was also lower, although statistically insignificant. All parameters increased significantly after MLPVB as follows: height from -0.42 before surgery to -0.12 (P = .027) at 5 to 12 months and -0.14 (P = .026) at 13 to 24 months; weight from -0.49 before surgery to 0.03 (P < .001) at 5 to 12 months and 0.35 (P < .001) at 13 to 24 months; and BMI from -0.22 before surgery to 0.17 (P = .001) at 5 to 12 months and 0.48 (P < .001) at 13 to 24 months. Restoration of portal blood flow to the liver by MLPVB improves growth in children with EHPVO.


Methadone, Buprenorphine, and Naltrexone for the Treatment of Opioid Use Disorder in Pregnant Women.
Pregnant women with opioid use disorder can be treated with methadone, buprenorphine, or naltrexone to reduce opioid use and improve retention to treatment. In this review, we compare the pregnancy outcomes of methadone, buprenorphine, and naltrexone in clinical trials and discuss the potential behavioral and developmental effects of these agents seen in offspring in animal studies. Important clinical considerations in the management of opioid use disorder in pregnant women and their infants are also discussed. Outside of pregnancy, buprenorphine is used in combination with naloxone to reduce opioid abuse and diversion. During pregnancy, however, the use of buprenorphine as a single agent is preferred to prevent prenatal naloxone exposure. Both methadone and buprenorphine are widely used to treat opioid use disorder; however, compared with methadone, buprenorphine is associated with shorter treatment duration, less medication needed to treat neonatal abstinence syndrome (NAS) symptoms, and shorter hospitalizations for neonates. Despite being the standard of care, medication-assisted treatment with methadone or buprenorphine is still underused, making it apparent that more options are necessary. Naltrexone is not a first-line treatment primarily because both detoxification and an opioid-free period are required. More research is needed to determine naltrexone safety and benefits in pregnant women. Animal studies suggest that changes in pain sensitivity, developmental processes, and behavioral responses may occur in children born to mothers receiving methadone, buprenorphine, or naltrexone and is an area that warrants future studies.


A fully automated Drosophila olfactory classical conditioning and testing system for behavioral learning and memory assessment.
Aversive olfactory classical conditioning has been the standard method to assess Drosophila learning and memory behavior for decades, yet training and testing are conducted manually under exceedingly labor-intensive conditions. To overcome this severe limitation, a fully automated, inexpensive system has been developed, which allows accurate and efficient Pavlovian associative learning/memory analyses for high-throughput pharmacological and genetic studies. The automated system employs a linear actuator coupled to an odorant T-maze with airflow-mediated transfer of animals between training and testing stages. Odorant, airflow and electrical shock delivery are automatically administered and monitored during training trials. Control software allows operator-input variables to define parameters of Drosophila learning, short-term memory and long-term memory assays. The approach allows accurate learning/memory determinations with operational fail-safes. Automated learning indices (immediately post-training) and memory indices (after 24h) are comparable to traditional manual experiments, while minimizing experimenter involvement. The automated system provides vast improvements over labor-intensive manual approaches with no experimenter involvement required during either training or testing phases. It provides quality control tracking of airflow rates, odorant delivery and electrical shock treatments, and an expanded platform for high-throughput studies of combinational drug tests and genetic screens. The design uses inexpensive hardware and software for a total cost of ∼$500US, making it affordable to a wide range of investigators. This study demonstrates the design, construction and testing of a fully automated Drosophila olfactory classical association apparatus to provide low-labor, high-fidelity, quality-monitored, high-throughput and inexpensive learning and memory behavioral assays.


Preparing Laboratory and Real-World EEG Data for Large-Scale Analysis: A Containerized Approach.
Large-scale analysis of EEG and other physiological measures promises new insights into brain processes and more accurate and robust brain-computer interface models. However, the absence of standardized vocabularies for annotating events in a machine understandable manner, the welter of collection-specific data organizations, the difficulty in moving data across processing platforms, and the unavailability of agreed-upon standards for preprocessing have prevented large-scale analyses of EEG. Here we describe a "containerized" approach and freely available tools we have developed to facilitate the process of annotating, packaging, and preprocessing EEG data collections to enable data sharing, archiving, large-scale machine learning/data mining and (meta-)analysis. The EEG Study Schema (ESS) comprises three data "Levels," each with its own XML-document schema and file/folder convention, plus a standardized (PREP) pipeline to move raw (Data Level 1) data to a basic preprocessed state (Data Level 2) suitable for application of a large class of EEG analysis methods. Researchers can ship a study as a single unit and operate on its data using a standardized interface. ESS does not require a central database and provides all the metadata data necessary to execute a wide variety of EEG processing pipelines. The primary focus of ESS is automated in-depth analysis and meta-analysis EEG studies. However, ESS can also encapsulate meta-information for the other modalities such as eye tracking, that are increasingly used in both laboratory and real-world neuroimaging. ESS schema and tools are freely available at www.eegstudy.org and a central catalog of over 850 GB of existing data in ESS format is available at studycatalog.org. These tools and resources are part of a larger effort to enable data sharing at sufficient scale for researchers to engage in truly large-scale EEG analysis and data mining (BigEEG.org).


Symptomatic HPV-related neovaginal lesions in transgender women: case series and review of literature.
Worldwide, transgender women are an at-risk population for contracting sexually transmitted infections. Little information exists on symptoms and characteristics of neovaginal human papillomavirus (HPV) infections and associated diseases. We describe a case series of transgender women with symptomatic HPV-related neovaginal lesions and a review of current literature. Transgender women with symptomatic HPV-related neovaginal lesions were identified from a departmental database comprising clinical and outpatient data on transgender women who underwent vaginoplasty between 1990 and 2015. HPV status was determined on excision and biopsy specimens by HPV DNA testing using GP5+6+-PCR and p16INK4A immunohistochemistry. Current literature was reviewed using the MEDLINE and EMBASE databases. This case series includes four transgender women with symptomatic, HPV-related neovaginal lesions. Two women presented with neovaginal and neovulvar pain and condylomata/leukoplakia, which were excised. These lesions showed moderate-to-severe dysplasia at histopathological examination, and were positive for high-risk HPV (hrHPV) and p16INK4A. Recurrence occurred in one patient and was treated with laser evaporation. Two women presented with neovaginal coital pain, neovaginal bleeding and condylomata. Neovulvar lesions were treated with podophyllotoxin. Neovaginal lesions were excised or evaporated. These lesions were low-risk HPV (lrHPV) positive. The literature search shows treatment options varying from conservative, topical podophyllotoxin to excision or laser evaporation under general anaesthesia. Neovaginal HPV infection can lead to benign condylomata (lrHPV) and various grades of dysplasia (hrHPV). We advise physicians to consider HPV infection and associated lesions in transgender women with otherwise unexplainable neovaginal pain or bleeding after vaginoplasty.


Photo-controllable Ultralong Room-Temperature Phosphorescence: State of the Art.
In this concept, we showcase the upsurge in the studies of dynamic ultralong room-temperature phosphorescence (RTP) materials containing inorganic and/or organic components as versatile photo-responsive platforms. The goal is to provide a comprehensive analysis of photo-controllable RTP, and meanwhile delve into the underlying RTP properties of various classes of photochromic materials including metal-organic complexes, organic-inorganic co-crystals, purely organic small molecules and organic polymers. In particular, the design principles governing the integration of the photochromic and RTP moieties within a single material system, and the tuning of dynamic RTP in response to light are emphasized. As such, this concept sheds light on the challenges and opportunities of using these tunable RTP materials for potential applications in optoelectronics, particularly highlighting their use of reversible information encryption, erasable light printing and rewritable smart paper.


Polyphasic taxonomy of the genus vibrio: numerical taxonomy of Vibrio cholerae, Vibrio parahaemolyticus, and related Vibrio species.
A set of 86 bacterial cultures, including 30 strains of Vibrio cholerae, 35 strains of V. parahaemolyticus, and 21 representative strains of Pseudomonas, Spirillum, Achromobacter, Arthrobacter, and marine Vibrio species were tested for a total of 200 characteristics. Morphological, physiological, and biochemical characteristics were included in the analysis. Overall deoxyribonucleic acid (DNA) base compositions and ultrastructure, under the electron microscope, were also examined. The taxonomic data were analyzed by computer by using numerical taxonomy programs designed to sort and cluster strains related phenetically. The V. cholerae strains formed an homogeneous cluster, sharing overall S values of >/=75%. Two strains, V. cholerae NCTC 30 and NCTC 8042, did not fall into the V. cholerae species group when tested by the hypothetical median organism calculation. No separation of "classic" V. cholerae, El Tor vibrios, and nonagglutinable vibrios was observed. These all fell into a single, relatively homogeneous, V. cholerae species cluster. V. parahaemolyticus strains, excepting 5144, 5146, and 5162, designated members of the species V. alginolyticus, clustered at S >/=80%. Characteristics uniformly present in all the Vibrio species examined are given, as are also characteristics and frequency of occurrence for V. cholerae and V. parahaemolyticus. The clusters formed in the numerical taxonomy analyses revealed similar overall DNA base compositions, with the range for the Vibrio species of 40 to 48% guanine plus cytosine. Generic level of relationship of V. cholerae and V. parahaemolyticus is considered dubious. Intra- and intergroup relationships obtained from the numerical taxonomy studies showed highly significant correlation with DNA/DNA reassociation data.


Gluten-sensitive enteropathy. Immunoglobulin G heavy-chain (Gm) allotypes and the immune response to wheat gliadin.
Anti-gliadin antibody was measured by radioimmunoassay in 30 Caucasians with gluten-sensitive enteropathy (GSE). 22 GSE patients maintained on a gluten-free diet for 1.5 to 20 yr (mean duration 76 mo) had elevated serum concentrations of IgG antigliadin antibody. Among GSE patients on a gluten-free diet, antigliadin antibody was seen only in those having the chromosome 14-encoded IgG immunoglobulin heavy chain allotype marker G2m(n). IgG antigliadin antibody was found in GSE patients with G2m(n) regardless of whether the HLA-B8 and/or -DR3 major histocompatibility complex antigens that occur frequently in GSE were present. No patient lacking G2m(n) had significant levels of antigliadin antibody. The association between antigliadin antibody and the immunoglobulin heavy chain allotype marker G2m(n) in GSE patients likely reflects the presence of Gmn-linked variable region genes or Gmn-linked genes that regulate variable region gene expression.


Efficacy of biological therapies and small molecules in moderate to severe ulcerative colitis: systematic review and network meta-analysis.
Biological therapies and small molecules continue to be evaluated in moderate to severely active ulcerative colitis, but are often studied in placebo-controlled trials, meaning their relative efficacy and safety is unknown. We examined this in a network meta-analysis. We searched the literature to October 2021 to identify eligible trials. We judged efficacy using clinical remission, endoscopic improvement, or clinical response, and according to previous exposure or non-exposure to antitumour necrosis factor (TNF)-α therapy. We also assessed safety. We used a random effects model and reported data as pooled relative risks (RRs) with 95% CIs. Interventions were ranked according to their P-score. We identified 28 trials (12 504 patients). Based on failure to achieve clinical remission, upadacitinib 45 mg once daily ranked first versus placebo (RR 0.73; 95% CI 0.68 to 0.80, P-score 0.98), with infliximab 5 mg/kg and 10 mg/kg second and third, respectively. Upadacitinib ranked first for clinical remission in both patients naïve to anti-TNF-α drugs (RR 0.69; 95% CI 0.61 to 0.78, P-score 0.99) and previously exposed (RR 0.78; 95% CI 0.72 to 0.85, P-score 0.99). Upadacitinib was superior to almost all other drugs in these analyses. Based on failure to achieve endoscopic improvement infliximab 10 mg/kg ranked first (RR 0.61; 95% CI 0.51 to 0.72, P-score 0.97), with upadacitinib 45 mg once daily, second, and infliximab 5 mg/kg third. Upadacitinib was more likely to lead to adverse events, but serious adverse events were no more frequent, and withdrawals due to adverse events were significantly lower than with placebo. Infections were significantly more likely with tofacitinib than placebo (RR 1.41; 95% CI 1.03 to 1.91). In a network meta-analysis, upadacitinib 45 mg once daily ranked first for clinical remission in all patients, patients naïve to anti-TNF-α drugs and patients previously exposed. Infliximab 10 mg/kg ranked first for endoscopic improvement. Most drugs were safe and well tolerated.


Use of monoclonal antibody against human neutrophil elastase in normal and leukaemic myeloid cells.
A monoclonal antibody, NP57, was produced and used against the neutrophil granule protein elastase, which selectively stain neutrophils in cryostat and paraffin wax sections. The antibody stains neutrophils and a subpopulation of monocytes in blood smears and neutrophil precursors in bone marrow smears, and gives positive reactions with the cell lines HL60 and U-937. It labelled the blast cells in 68% of cases of acute myeloid leukaemia (M1-M5) but was unreactive with all cases of lymphoid leukaemias. Most of the elastase negative myeloid leukaemias were labelled by monoclonal anti-myeloperoxidase (antibody MPO-7) as were cells from the promyelocytic line HL60. No cases of myeloid leukaemia showed the opposite pattern--that is elastase positive, myeloperoxidase negative, suggesting that the production of myeloperoxidase precedes the onset of elastase synthesis during myeloid maturation. The anti-elastase antibody NP57 is a useful addition to the range of monoclonal antibodies available for the differential diagnosis of acute leukaemia by alkaline phosphatase-antialkaline phosphatase (APAAP) labelling of cell smears; it may also be of value for the histopathological diagnosis of tumour deposits in myeloid leukaemia and for the detection of neutrophils in paraffin sections.


Nurse-mediated serum cholesterol reduction and health locus of control--a device for targeting health promotion?
Varying intensities of nurse-mediated health education advice were administered to subjects over a three-month period. Mean serum total cholesterol was calculated for each group at the outset and completion of the study. A multidimensional health locus of control (MHLC) scales questionnaire was self-completed by subjects at the outset. A highly significant association between internality and reduction in serum total cholesterol in the high-intensity intervention group was observed. The completion of a MHLC scale questionnaire may assist health professionals in identifying which subjects may most benefit from high-intensity health education advice when raised serum total cholesterol is prevalent.


ERRATUM: Unexpected Serious Cardiac Arrhythmias in the Setting of Loperamide Abuse.
Loperamide (Imodium) is a non-prescription opioid receptor agonist available over-the-counter for the treatment of diarrhea. When ingested in excessive doses, loperamide can penetrate the blood-brain barrier and is reported to produce euphoria, central nervous system and respiratory depression, and cardiotoxicity. There is an emerging trend in its use among drug abusers for its euphoric effects or for self-treatment of opioid withdrawal. We report a case of ventricular dysrhythmias associated with loperamide abuse in a 28-year-old man who substituted loperamide for the opioids that he used to abuse. [Full article available at http://rimed.org/rimedicaljournal-2017-04.asp, free with no login].


Inclusion of Scar/WAVE3 in a similar complex to Scar/WAVE1 and 2.
The Scar/WAVE family of proteins mediates signals to actin assembly by direct activation of the Arp2/3 complex. These proteins have been characterised as major regulators of lamellipodia formation downstream of Rac activation and as members of large protein complexes. We have investigated the interactions of the three human Scar/WAVE isoforms with several previously described binding partners for Scar/WAVE 1 or 2. We find that all three Scar/WAVE isoforms behave similarly and are likely to participate in the same kinds of protein complexes that regulate actin assembly. Differences between Scar/WAVE proteins are therefore likely to be at the level of tissue distribution or subtle differences in the affinity for specific binding partners.


Implementation of a surgical unit-based safety programme in African hospitals: a multicentre qualitative study.
A Surgical Unit-based Safety Programme (SUSP) has been shown to improve perioperative prevention practices and to reduce surgical site infections (SSI). It is critical to understand the factors influencing the successful implementation of the SUSP approach in low- and middle-income settings. We undertook a qualitative study to assess viability, and understand facilitators and barriers to implementing the SUSP approach in 5 African hospitals. Qualitative study based on interviews with individuals from all hospitals participating in a WHO-coordinated before-after SUSP study. The SUSP intervention consisted of a multimodal strategy including multiple SSI prevention measures combined with an adaptive approach aimed at improving teamwork and safety culture. Thirteen interviews (5 head surgeons, 3 surgeons, 5 nurses) were conducted with staff from five hospital sites. Identified facilitators included influential individuals (intrinsic motivation of local SUSP teams, boundary spanners, multidisciplinary engagement, active leadership support), peer-to-peer learning (hospital networking and positive deviance, benchmarking), implementation fitness (enabling infrastructures, momentum from previous projects), and timely feedback of infection rates and process indicators. Barriers (organisational 'constipators', workload, mistrust, turnover) and local solutions to these were also identified. Participating hospitals benefitted from the SUSP programme structures (e.g. surveillance, hospital networks, formation of multidisciplinary teams) and adaptive tools (e.g. learning from defects, executive rounds guide) to change perceptions around patient safety and improve behaviours to prevent SSI. The combination of technical and adaptive elements represents a promising approach to facilitate the introduction of evidence-based best practices and to improve safety culture through local team engagement in resource-limited settings.


Reactive oxygen species, apoptosis, antimicrobial peptides and human inflammatory diseases.
Excessive free radical generation, especially reactive oxygen species (ROS) leading to oxidative stress in the biological system, has been implicated in the pathogenesis and pathological conditions associated with diverse human inflammatory diseases (HIDs). Although inflammation which is considered advantageous is a defensive mechanism in response to xenobiotics and foreign pathogen; as a result of cellular damage arising from oxidative stress, if uncontrolled, it may degenerate to chronic inflammation when the ROS levels exceed the antioxidant capacity. Therefore, in the normal resolution of inflammatory reactions, apoptosis is acknowledged to play a crucial role, while on the other hand, dysregulation in the induction of apoptosis by enhanced ROS production could also result in excessive apoptosis identified in the pathogenesis of HIDs. Apparently, a careful balance must be maintained in this complex environment. Antimicrobial peptides (AMPs) have been proposed in this review as an excellent candidate capable of playing prominent roles in maintaining this balance. Consequently, in novel drug design for the treatment and management of HIDs, AMPs are promising candidates owing to their size and multidimensional properties as well as their wide spectrum of activities and indications of reduced rate of resistance.


Evaluation of a new fusion antigen, cd loop and HAP2-GCS1 domain (cd-HAP) of Plasmodium falciparum Generative Cell Specific 1 antigen formulated with various adjuvants, as a transmission blocking vaccine.
Malaria is a major global health challenge, and for the elimination and eradication of this disease, transmission-blocking vaccines (TBVs) are a priority. Plasmodium falciparum Generative Cell Specific 1 (PfGCS1), a promising TBV candidate, is essential for gamete fertilization. The HAP2-GCS1 domain of this antigen as well as its cd loop could induce antibodies that partially inhibit transmission of P. falciparum. In the current study, a new synthetic fusion antigen containing cd loop and HAP2-GCS1 domain (cd-HAP) of PfGCS1 was evaluated as a transmission blocking vaccine candidate. Initially, the profile of naturally acquired IgG antibodies to the cd-HAP antigen was analysed in Iranian individuals infected with P. falciparum, to confirm that this new fusion protein has the appropriate structure containing common epitopes with the native form of PfGCS1. Then, the immunogenicity of cd-HAP was evaluated in BALB/c mice, using different adjuvant systems such as CpG, MPL, QS-21, and a combination of them (CMQ). Furthermore, the blocking efficacy of polyclonal antibodies induced against these formulations was also assessed by oocyst intensity and infection prevalence in the Standard Membrane Feeding Assay (SMFA). The naturally acquired antibodies (dominantly IgG1 and IgG3 subclasses) induced in P. falciparum-infected individuals could recognize the cd-HAP antigen which implies that the new fusion protein has a proper conformation that mimics the native structure of PfGCS1. Concerning the immunogenicity of cd-HAP antigen, the highest IgG levels and titers, by a Th1-type immune profile, and elevated antibody avidity were induced in mice immunized with the cd-HAP antigen formulated with a combination of adjuvants (P < 0.0001). Additionally, cytokine profiling of the immunized mice displayed that a high level of IFN-γ response, a Th1-type immune response, was produced by splenocytes from immunized mice that received cd-HAP antigen in combination with CMQ adjuvants (P < 0.0001). This formulation of cd-HAP antigen with CMQ adjuvants could reduce oocyst intensity and infection prevalence by 82%, evidenced by the SMFA and hold significant implications for future malaria vaccine development. Altogether, the results showed that cd-HAP antigen formulated with a combination of the adjuvants (CMQ), could be a promising formulation to develop a PfGCS1-based transmission-blocking vaccine.


Improved genome assembly and pan-genome provide key insights into eggplant domestication and breeding.
Eggplant (Solanum melongena L.) is an important horticultural crop and one of the most widely grown vegetables from the Solanaceae family. It was domesticated from a wild, prickly progenitor carrying small, round, non-anthocyanic fruits. We obtained a novel, highly contiguous genome assembly of the eggplant '67/3' reference line, by Hi-C retrofitting of a previously released short read- and optical mapping-based assembly. The sizes of the 12 chromosomes and the fraction of anchored genes in the improved assembly were comparable to those of a chromosome-level assembly. We resequenced 23 accessions of S. melongena representative of the worldwide phenotypic, geographic, and genetic diversity of the species, and one each from the closely related species Solanum insanum and Solanum incanum. The eggplant pan-genome contained approximately 51.5 additional megabases and 816 additional genes compared with the reference genome, while the pan-plastome showed little genetic variation. We identified 53 selective sweeps related to fruit color, prickliness, and fruit shape in the nuclear genome, highlighting selection leading to the emergence of present-day S. melongena cultivars from its wild ancestors. Candidate genes underlying the selective sweeps included a MYBL1 repressor and CHALCONE ISOMERASE (for fruit color), homologs of Arabidopsis GLABRA1 and GLABROUS INFLORESCENCE STEMS2 (for prickliness), and orthologs of tomato FW2.2, OVATE, LOCULE NUMBER/WUSCHEL, SUPPRESSOR OF OVATE, and CELL SIZE REGULATOR (for fruit size/shape), further suggesting that selection for the latter trait relied on a common set of orthologous genes in tomato and eggplant.


Detection of hepatitis A virus in sewage sludge by antigen capture polymerase chain reaction.
Antigen capture polymerase chain reaction (PCR) was tested as a sensitive and rapid method for detecting hepatitis A virus (HAV) in raw sewage sludge. The antigen capture PCR was performed both with and without solid-phase virus-catching monoclonal antibodies. Similar results proved that both methods were equally sensitive. Sewage sludge samples from different regions in Germany were examined for evidence of HAV contamination by antigen capture PCR. This method of detection was compared with that used in a previous study of these sewage sludge samples, in which the HAV was detected through indirect immunofluorescence after cell culture inoculation. The results obtained by antigen capture PCR matched those obtained in the earlier cell culture investigations, when HAV was detected in raw as well as digested sewage sludge samples. The advantage of the PCR method, however, lies in the fact that it needs only two days while the cell culture propagation of HAV takes about 8 to 10 weeks.


A study on prevalence of chewing form of tobacco and existing quitting patterns in urban population of jamnagar, gujarat.
Awareness towards tobacco hazards has increased with time but its role alone towards cessation is questionable. With widespread menace of tobacco in developing countries like India, not much tobacco chewing prevalence and their quitting patterns data are available in urban Saurashtra region. 1. To find out prevalence of various forms of chewing tobacco and quitting attitudes in urban Jamnagar. 2. To study quitting patterns in relation with age of habit initiation, family background and habit duration. It was a cross-sectional study involving 2513 individuals as study population by 30-cluster sampling method. The study was carried out between June 2007 and March 2008. Pre-set, pre-tested questionnaire was used for interview purpose and the statistical analysis was done on proportion basis. About 37.2% of study population was ever-tobacco-chewers; 32.9% of them were current-chewers and 4.3% were quitters. Approximately 28.4% of current-consumers were willing to quit. Mawa-masala (63.7%) and Gutka (57.6%) were preferred forms of chewing tobacco and 57.5% of the current-chewers chewed tobacco six to eight times a day. Tobacco initiation age between 20 and 30 years was commoner among quitters (84.2%), while a little younger in current-consumers (76.5%). About 58.3% quitters and 74.0% chewers showing willingness to quit had not consumed tobacco for more than five years, 63.8% of current-chewers had a family member consuming tobacco. With initiation of health problems, 72.2% subjects quit and 55.5% of them already knew about health hazards. Every 4 out of 10 residents was found to be exposed to chewing tobacco. With Mawa-masala and Gutka being the predominant forms, habit onset in late adolescence, years of consumption and family exposure seem to be hampering quitting. Awareness about tobacco hazards alone does not appear to be resulting in successful quitting.


Cryptic diversity and female host specificity in a parasitoid where the sexes utilize hosts from separate orders.
Investigating complex parasitic life cycles is important for understanding the major fitness components that drive the evolution of host-parasite systems. The rare condition of heterotrophic heteronomy, in which the sexes utilize disparate host taxa, is a poorly understood complex parasitic lifestyle. One of only two known examples occurs in the Myrmecolacidae, an unusual family of the parasitoid order Strepsiptera (Insecta), in which males parasitize ants while females parasitize grasshoppers, crickets, and praying mantids. Here, we reconstruct the evolutionary pattern and timescale of host-use in a set of morphologically cryptic myrmecolacid taxa currently identified as Caenocholax fenyesi. We find that (i) C. fenyesi contains at least ten cryptic lineages consistent with separate species; (ii) Fossil evidence suggests a very low molecular clock rate and an ancient origin for cryptic lineages; (iii) Diversity among Caenocholax species is partitioned by geography and host association of the female; and (iv) Switches in host usage are uncoupled between the sexes, with changes in female host preference accompanying diversification. This study represents the first phylogeographical analysis of any strepsipteran, and the first molecular examination of host-use for a heterotrophic heteronomous taxon. Our results have implications for the understanding of evolution, host usage and estimated species richness in parasitic taxa.


[Effect of environmental chemicals on the genes and the gene expression].
Chemicals act on biological molecules and affect their functions. DNA is one of the most important targets, damaging of which could lead to diverse diseases including cancer. The mode of action of chemicals to DNA contains chemical reaction and protein factor-mediated modulation of the function. In this review, these actions are described in view of effects of chemicals on DNA. First, oxidative damage of DNA is described in several cases of chemicals focusing on its mechanisms involving metals such as copper. We have demonstrated: DNA binding of copper ions prior to reduction-oxidation reaction is crucial for the damaging, probably due to the proximal attack of reactive oxygen species; reduction of the bound copper induces a conformational change of DNA strand through rearrangement of copper-coordination geometry; RNA, another nucleic acid, is more liable to oxidative damage than DNA. Impact of RNA damage on oxidative stress-related diseases is discussed. Second, a group of chemicals called endocrine disruptors is described. Phthalate esters are ubiquitous endocrine disruptors of which mechanisms are still elusive. Here, we present our research performed for elucidation of the active metabolite and molecular target. Novel candidates of active metabolite are suggested. Finally, toxicological activity dynamics are described, showing several chemicals exert toxic potential by structural alteration in the environment, metabolism, or both. These imply gene-environment interactions that would underlie various diseases induced by environmental chemicals.


Comparison of the Qualitative Chemical Composition of Extracts from Ageratina havanensis Collected in Two Different Phenological Stages by FIA-ESI-IT-MS" and UPLC/ESI-MS": Antiviral Activity.
The flowers and leaves of Ageratina havanensis (Kunth) R. M. King & H. Robinson are traditionally used as a tea to cure several diseases. The production of active secondary metabolites can be affected by several environmental factors such as climate, altitude, rainfall, phenological stage and other conditions that may influence the growth of plants. In this sense, the development of a methodology to compare the chemical composition of plant -extracts is needed. The qualitative chemical composition of the ethyl acetate extracts of flowers and leaves, collected in both reproductive and non-reproductive season, was determined by.flow injection analysis-electrospray ionization-ion trap tandem mass spectrometry (FIA-ESI-IT-MS") and ultra-high-performance liquid chromatography coupled to electrospray negative ionization mass spectrometry (UPLC/ESI-MS"). The qualitative chemical composition of the ethyl acetate extracts of flowers and leaves was very similar in all cases. Also the antiviral activity of flowers against human herpes simplex viruses type I and 2 (HSV-1, HSV-2) (Herpesviridae) was analyzed. Three glucoside flavonoids were isolated from the ethyl acetate extract of the leaves of A. havanensis collected in flowering season using chromatographic methods and their structures were elucidated by physical and spectroscopic data measurements, and by comparing the obtained data with previously published values. The compounds were identified as 3-Ο-β-D-glucosyl-7-methoxyaromadendrin (5), 7-Ο-β-D--glucosyl-4'- dihydroxy-5-methoxyflavanone (6) and 5-O-β-D-glucosylsakuranetin (7); this is the first report of the isolation of these compounds in the Asteraceae family. Since the qualitative composition of the extracts of A. havanensis was similar in all cases, it can be expected that the ethyl acetate extract of the leaves collected in the non-reproductive season has anti-herpetic activity similar to that obtained in the reproductive season.


Calculation of proper energy barriers for atomistic kinetic Monte Carlo simulations on rigid lattice with chemical and strain field long-range effects using artificial neural networks.
In this paper we take a few steps further in the development of an approach based on the use of an artificial neural network (ANN) to introduce long-range chemical effects and zero temperature relaxation (elastic strain) effects in a rigid lattice atomistic kinetic Monte Carlo (AKMC) model. The ANN is trained to predict the vacancy migration energies as calculated given an interatomic potential with the nudged elastic band method, as functions of the local atomic environment. The kinetics of a single-vacancy migration is thus predicted as accurately as possible, within the limits of the given interatomic potential. The detailed procedure to apply this method is described and analyzed in detail. A novel ANN training algorithm is proposed to deal with the necessarily large number of input variables to be taken into account in the mathematical regression of the migration energies. The application of the ANN-based AKMC method to the simulation of a thermal annealing experiment in Fe-20%Cr alloy is reported. The results obtained are found to be in better agreement with experiments, as compared to already published simulations, where no atomic relaxation was taken into account and chemical effects were only heuristically allowed for.


Chlorhexidine gluconate 0.02% as adjunct to primary treatment for corneal bacterial ulcers.
It is common practice to use topical antiseptic formulations prior to specific therapy in superficial infections and injuries, but not in corneal bacterial ulcers. There is accumulating evidence proving chlorhexidine gluconate 0.02%, an antiseptic agent, as an effective treatment for infectious keratitis. To investigate the safety and efficacy of chlorhexidine gluconate 0.02% as an adjunct therapy for corneal bacterial ulcers. Twenty-six patients with corneal bacterial ulcers were treated with standard empirical antibiotic treatment. The study group was treated with chlorhexidine gluconate 0.02% while controls received placebo for one week. The patients were followed for at least 1 month. No allergic or toxic reactions were noted. Although a higher baseline severity of ulcers existed in the study group, no differences were found in final vision, scarring extent, or recovery duration. Chlorhexidine gluconate 0.02% may improve the clinical course of corneal ulcers.


Near-Infrared Spectroscopy - Electroencephalography-Based Brain-State-Dependent Electrotherapy: A Computational Approach Based on Excitation-Inhibition Balance Hypothesis.
Stroke is the leading cause of severe chronic disability and the second cause of death worldwide with 15 million new cases and 50 million stroke survivors. The poststroke chronic disability may be ameliorated with early neuro rehabilitation where non-invasive brain stimulation (NIBS) techniques can be used as an adjuvant treatment to hasten the effects. However, the heterogeneity in the lesioned brain will require individualized NIBS intervention where innovative neuroimaging technologies of portable electroencephalography (EEG) and functional-near-infrared spectroscopy (fNIRS) can be leveraged for Brain State Dependent Electrotherapy (BSDE). In this hypothesis and theory article, we propose a computational approach based on excitation-inhibition (E-I) balance hypothesis to objectively quantify the poststroke individual brain state using online fNIRS-EEG joint imaging. One of the key events that occurs following Stroke is the imbalance in local E-I (that is the ratio of Glutamate/GABA), which may be targeted with NIBS using a computational pipeline that includes individual "forward models" to predict current flow patterns through the lesioned brain or brain target region. The current flow will polarize the neurons, which can be captured with E-I-based brain models. Furthermore, E-I balance hypothesis can be used to find the consequences of cellular polarization on neuronal information processing, which can then be implicated in changes in function. We first review the evidence that shows how this local imbalance between E-I leading to functional dysfunction can be restored in targeted sites with NIBS (motor cortex and somatosensory cortex) resulting in large-scale plastic reorganization over the cortex, and probably facilitating recovery of functions. Second, we show evidence how BSDE based on E-I balance hypothesis may target a specific brain site or network as an adjuvant treatment. Hence, computational neural mass model-based integration of neurostimulation with online neuroimaging systems may provide less ambiguous, robust optimization of NIBS, and its application in neurological conditions and disorders across individual patients.


Management and control of coccidiosis in poultry.
Poultry coccidiosis is an intestinal infection caused by an intracellular parasitic protozoan of the genus Eimeria. Coccidia-induced gastrointestinal inflammation results in large economic losses, hence finding methods to decrease its prevalence is critical for industry participants and academic researchers. It has been demonstrated that coccidiosis can be effectively controlled and managed by employing anticoccidial chemical compounds. However, as a result of their extensive use, anticoccidial drug resistance in Eimeria species has raised concerns. Phytochemical/herbal medicines (Artemisia annua, Bidens pilosa, and garlic) seem to be a promising strategy for preventing coccidiosis, in accordance with the "anticoccidial chemical-free" standards. The impact of herbal supplements on poultry coccidiosis is based on the reduction of oocyst output by preventing the proliferation and growth of Eimeria species in chicken gastrointestinal tissues and lowering intestinal permeability via increased epithelial turnover. This review provides a thorough up-to-date assessment of the state of the art and technologies in the prevention and treatment of coccidiosis in chickens, including the most used phytochemical medications, their mode of action, and the applicable legal framework in the European Union.


Ultrasound-guided Morcellation During Difficult Holmium Laser Enucleation of the Prostate.
To demonstrate how bladder ultrasound can be useful in completing morcellation during difficult Holmium Laser Enucleation of the Prostate (HoLEP). As HoLEP has emerged as a standard of care for the treatment of benign prostatic hyperplasia, multiple studies have reported the potentially catastrophic complication of bladder injury during morcellation. This video aims to assist any urologist performing HoLEP by providing step-by-step instruction for using ultrasound to complete morcellation safely. Enucleation is performed using a 26-French continuous flow scope, off-set laser bridge with a laser stabilization catheter, and a 550 µm holmium laser fiber. Once the median and lateral lobes have been enucleated, the outer sheath is removed and the nephroscope is inserted to facilitate morcellation. Under dual inflow irrigation, the Piranha morcellator (Richard Wolf, Knittlingen, Germany) is introduced and set to the manufacturer's recommended settings of 1500 rpm. A 3.5-MHz convex abdominal ultrasound transducer (Hitachi Prosound Alpha 7; Hitachi Aloka Medical America, Wallingford, CT) under B-mode is used to visualize the bladder, predominantly in the sagittal orientation. Morcellation proceeds under simultaneous ultrasound and direct cystoscopic guidance. The distended bladder is visualized concurrently with the ultrasound and via the nephroscope as the Piranha engages the adenoma and begins morcellation. Once the adenoma is engaged, the operator then drops their hands to place the morcellator in the center of the bladder. Ultrasound provides real-time feedback as to the location of the morcellator in relation to the adenoma and bladder. This video highlights the use of intraoperative bladder ultrasound as a visual aid to assist during the morcellation portion of HoLEP. This proof of concept demonstrates that ultrasound can be an additional tool to utilize during difficult cases when cystoscopic visualization during morcellation is limited.


Hypothesis-driven candidate genes for schizophrenia compared to genome-wide association results.
Candidate gene studies have been a key approach to the genetics of schizophrenia (SCZ). However, the results of these studies are confusing and no genes have been unequivocally implicated. The hypothesis-driven candidate gene literature can be appraised by comparison with the results of genome-wide association studies (GWAS). We describe the characteristics of hypothesis-driven candidate gene studies from the SZGene database, and use pathway analysis to compare hypothesis-driven candidate genes with GWAS results from the International Schizophrenia Consortium (ISC). SZGene contained 732 autosomal genes evaluated in 1374 studies. These genes had poor statistical power to detect genetic effects typical for human diseases, assessed only 3.7% of genes in the genome, and had low marker densities per gene. Most genes were assessed once or twice (76.9%), providing minimal ability to evaluate consensus across studies. The ISC studies had 89% power to detect a genetic effect typical for common human diseases and assessed 79% of known autosomal common genetic variation. Pathway analyses did not reveal enrichment of smaller ISC p values in hypothesis-driven candidate genes, nor did a comprehensive evaluation of meta-hypotheses driving candidate gene selection (SCZ as a disease of the synapse or neurodevelopment). The most studied hypothesis-driven candidate genes (COMT, DRD3, DRD2, HTR2A, NRG1, BDNF, DTNBP1 and SLC6A4) had no notable ISC results. We did not find support for the idea that the hypothesis-driven candidate genes studied in the literature are enriched for the common genetic variation involved in the etiology of SCZ. Larger samples are required to evaluate this conclusion definitively.


The pain cycle: implications for the diagnosis and treatment of pelvic pain syndromes.
The aim of the study was to report our results of sacral nerve stimulation in patients with pelvic pain after failed conservative treatment. From 1992 to August 1998 we treated 111 patients (40 males, 71 females, ages 46 +/- 16 years) with chronic pelvic pain. All patients with causal treatment were excluded from this study. Pelvic floor training, transcutaneous electrical nerve stimulation (TENS) and intrarectal or intravaginal electrostimulation were applied and sacral nerve stimulation was used for therapy-resistant pain. The outcome of conservative treatment and sacral nerve stimulation (VAS <3/10; >50% pain relief) was related to symptoms of voiding dysfunction and dyschezia, and urodynamic proof of dysfunctional voiding, not to the pain localization or treatment modality. Outcome was inversely related to neuropathic pain. When conservative treatment failed, a test stimulation of the S3 root was effective in 16/26 patients, and 11 patients were implanted successfully with a follow-up of 36 +/- 8 months. So far no late failures have been seen. A longer test stimulation is needed in patients with pelvic pain because of a higher incidence of initial false positive tests. Our conclusion is that sacral nerve stimulation is effective in the treatment of therapy-resistant pelvic pain syndromes linked to pelvic floor dysfunction.


Effects of cycloalkyl ring analogs of phencyclidine on behavior in rodents.
The purpose of the present experiments was to evaluate the effects of eliminating or varying the size of the cycloalkyl ring of phencyclidine (PCP) from 3 to 8 carbons while leaving the composition of the benzene and piperidine rings unaltered. Compounds were evaluated for their effectiveness in producing PCP-like discriminative stimuli and changes in pupil diameter in the rat and impaired motor performance on the Rotarod in the mouse. All modifications of the cycloalkyl ring of PCP significantly reduced the relative potencies of the cycloalkyl analogs, shortened their duration of action and also modified their spectra of action, including their effectiveness in producing PCP-like discriminative stimuli and miosis in the rat as well as ataxia in the mouse. The present results demonstrate that the cyclohexyl moiety of PCP is an absolute requirement for producing a full PCP-like spectrum of activity.


Global Anticoagulant Registry in the Field - Venous Thromboembolism (GARFIELD-VTE). Rationale and design.
Venous thromboembolism (VTE) is a common disorder associated with significant rates of morbidity and mortality. VTE management aims to reduce mortality, the risks of recurrence, and long-term complications. VTE treatment is evolving with the introduction of non-vitamin K antagonist anticoagulants (NOACs). The Global Anticoagulant Registry in the FIELD - Venous Thromboembolism (GARFIELD-VTE) is a prospective, multicentre, observational study that will enrol 10,000 patients treated for acute VTE from ~500 sites in 28 countries. Identified sites reflect the diversity of care settings, including hospital and outpatient settings. Patients will be managed according to local practices and followed for at least three years. The primary objective is to determine the extent to which VTE treatment varies in the real-world setting and to assess the impact of such variability on clinical and economic outcomes. Evolving patterns of care will be captured using two sequential cohorts. The GARFIELD-VTE registry will provide insights into the evolving global treatment patterns for VTE, both deep-vein thrombosis and pulmonary embolism. By enrolling patients from diverse care settings, the registry will provide information on adherence to national and international guidelines, identify good practice as well as treatment deficiencies, and relate patient outcomes to clinical management. The incidence of death, recurrent VTE, bleeding, post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension will be documented. By capturing information during and after anticoagulation treatment, the registry will not only define aspects of the natural history of VTE, but also its economic and societal impact at a regional and global level.


GPs' attitudes on a healthy lifestyle: a survey of GPs in Flanders.
Patients often consider health professionals to be role models for leading a healthy lifestyle but no data is available on tobacco, alcohol, or substance use among GPs in Flanders (northern Belgium). To estimate the prevalence of smoking, alcohol, and substance use among GPs, in order to determine factors that influence these habits and to elucidate GPs' attitudes toward a healthy lifestyle. Online survey-based study in Flanders, Belgium. Sociodemographic data and individual risk behaviour were collected by an anonymous self-administered questionnaire. GPs and family doctors in training were sent an email request between 1 April and 31 May 2011. Of 626 responders, 57% were male. The mean age was 45 years. Eight per cent (n = 50) were current smokers. Independent risk factors for smoking were: working alone, hazardous alcohol consumption, and smoking cannabis. Fourteen per cent (n = 86) consumed alcohol daily and 12% (n = 73) admitted at least one episode of binge drinking per month. Being male, cigarette smoking, cannabis use, and long working hours were associated with an increased likelihood of hazardous drinking. Sixteen per cent (n = 101) had used sleeping pills and 12% (n = 72) had used minor opiates as painkillers in the year before the study. Two-thirds (64%, n = 399) of GPs said they would be reluctant to seek medical help if they were misusing drugs or alcohol. Smoking is uncommon in Flemish GPs; in contrast, alcohol consumption is high. GPs who misuse substances will not seek help readily.


Alcohol availability and domestic violence.
The purpose of this study was to examine the relationship among sociodemographic variables, alcohol outlet density, and rate of domestic violence in New Jersey. Data were obtained for the 223 largest municipalities in the state and were examined using factor analysis and bivariate and multivariate analyses. Three sociodemographic factors were extracted through factor analysis. These explained 58% of the variance among municipalities in rates of domestic violence. One factor--termed social disadvantage--explained the greatest amount of unique variance (42%). Alcohol outlet density added nothing to the sociodemographic model and did not interact with any of the three sociodemographic factors. The findings show that, in the state of New Jersey, higher levels of alcohol outlet density are not geographically associated with higher rates of domestic violence. These findings may be due to limitations in the data sets employed in the study, limitations of the macrolevel analysis employed, and/or the complex nature of the relationship between alcohol use and domestic violence.


Molecular classification of diffuse gliomas.
In this study we assessed whether gliomas could be subdivided into different molecular subtypes by immunohistochemistry (IHC) reminiscent of those first described by Verhaak et al. in 2010 (classical, proneural, mesenchymal and neural). We also evaluated the prognostic significance of single molecular factors and searched for significant correlations between markers. In this study, we included 146 patients with glioblastomas (GBMs) and 26 with diffuse astrocytomas (DAs). The glioma samples were tested for PDGFRA, IDH1 R132H, CD44, p53, Ki-67, p21 and p27 expression. We found that gliomas could be subdivided into molecular subtypes by IHC. Fifty per cent of GBMs were of the proneural subtype, 18.5% of mesenchymal subtype and 31.5% were not otherwise classified. However, most of the DAs (92.3%) belonged to the proneural subtype. No prognostic role was found for the molecular subtypes, but predictive roles were noted. Both proneural and mesenchymal molecular subtypes showed a benefit from the addition of chemotherapy and radiotherapy; however, the mesenchymal subtype showed a greater response. Interestingly, the mesenchymal subtype did not receive any benefit from the addition of radiotherapy compared with palliative management and surgery alone. Regarding single molecular markers, only IDH1 R132H was found to have a prognostic role for GBMs. There was a trend towards better survival in tumours with lower PDGFRA expression (p = 0.066). In DAs, PDGFRA and Ki-67 expression had prognostic roles. The following statistically significant correlations were found in GBMs: Ki-67/p53, Ki-67/p27 and p53/PDGFRA; in DAs: p53/PDGFRA, CD44/PDGFRA, and p21/PDGFRA.


Risk of acute stroke in patients with retinal artery occlusion: a systematic review and meta-analysis.
To estimate the incidence of acute cerebral ischaemia detected by magnetic resonance imaging (MRI) in acute central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO) and transient monocular vision loss (TMVL). Studies reporting the incidence of acute cerebral ischaemia, detected by MRI, within 7 days from diagnosis of acute CRAO, BRAO and TMVL up to January 2019 were systematically searched for on Pubmed, Medline and Cochrane Library. Meta-analysis was performed using random effects model. The primary outcome was the pooled estimate of incidence of acute cerebral ischaemia in CRAO, BRAO and TMVL cohorts including both neurologically symptomatic and asymptomatic patients, expressed as a proportion along with 95% confidence intervals (CIs). The pooled estimate of incidence of asymptomatic acute cerebral ischaemia represented a secondary outcome measure. For the primary outcome, the pooled proportion of acute cerebral ischaemia was 0.30 (CI 0.24-0.36) in the CRAO cohort, and 0.25 (CI 0.16-0.37) in the BRAO cohort, without statistical heterogeneity. The rate of acute cerebral ischaemia was 11.8% in the TMVL cohort. For the secondary outcome, the pooled proportion of asymptomatic acute cerebral ischaemia was 0.22 (CI 0.16-0.28) in the CRAO cohort, 0.29 (CI 0.20-0.41) in the BRAO cohort and 0.08 (CI 0.05-0.15) in the TMVL cohort, with no statistical heterogeneity. 30% of patients with acute CRAO and 25% of patients with acute BRAO presented an acute cerebral ischaemia on MRI. Such high rates support a care pathway of prompt referral of such patients for neurological evaluation and brain imaging.


Improvement of myocardial lipid accumulation and prevention of PGC-1α induction by fenofibrate.
We recently demonstrated that fenofibrate induces the activities of citrate synthase and NADH oxidase in cardiac mitochondria. To further determine the molecular mechanisms underlying fenofibrate action, 8-week-old mice were administered fenofibrate (100 mg/kg/day) for 7 and 14 days, and the expression of genes involved in cardiac mitochondrial function, such as nuclear respiratory factor 1 transcript variant 2 (NRF-1-L) and 6 (NRF-1-S), mitochondrial outer membrane protein 40 (Tom40), lipoic acid synthetase (Lias), cytochrome b, medium-chain acyl-coenzyme A dehydrogenase (MCAD) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) was determined. Expression of PGC-1α, a key regulator of the entire fatty acid oxidation system, was significantly downregulated after 14 days of fenofibrate administration. Moreover, ventricular triglycerides were also accumulated following 14 days of fenofibrate administration. Thus, fenofibrate functions to improve myocardial lipid accumulation and to prevent PGC-1α induction, which is crucial for understanding the molecular mechanisms underlying fenofibrate action on the heart.


A guide to the use of Procedural Terminology for Psychiatrists.
The author emphasizes the potential benefits to patients, physicians, and third-party payers from systematic specification of services rendered by psychiatrists in direct patient care. Procedural Terminology for Psychiatrists provides a reporting system that appropriately reflects variations in skill, complexity, and levels of patient care services. The author suggest that reporting on the basis of specific procedures is an essential aspect in assuring quality care.


BEEF-vdW+U method applied to perovskites: thermodynamic, structural, electronic, and magnetic properties.
The recently developed BEEF-vdW exchange-correlation method provides a reasonably reliable description of both long-range van der Waals interactions and short-range covalent bonding between molecules and surfaces. However, this method still suffers from the excessive electron delocalization that is connected with the self-interaction error and, consequently, the calculated chemical and physical properties such as formation energy and band gap deviate markedly from the experimental values, especially when strongly correlated systems are under investigation. In this contribution, BEEF-vdW+U calculations have been performed to study the thermodynamic, structural, electronic, and magnetic properties of La-based perovskites. An effective interaction parameter [Formula: see text] and an energy adjustment [Formula: see text] are determined simultaneously by a mixing GGA and GGA+U method, where the enthalpy or Gibbs free energy of formation of oxides containing a transition metal in different oxidation states are fitted to available experimental data. The [Formula: see text] is found to have its origin in the fact that the GGA+U method gives rise to the offsets in the total energy that include not only the desired physical correction but also an arbitrary contribution. Calculated results indicate that the BEEF-vdW method provides a more accurate description of the bonding in the O2 molecule than the PBE method and has generally smaller [Formula: see text] values for the 3d-block transition metals, thereby giving rise to band gaps and magnetic moments that are in better agreement with the experimentally measured values.


Two state reactivity (TSR) and hydrogen tunneling reaction kinetics measured in the Co+ mediated decomposition of CH3CHO.
The electronic structure of a transition metal atom allows it to act as a catalytic active site by providing lower energy alternative pathways in chemical transformations. We have identified and kinetically characterized three such pathways in the title reaction. One is an adiabatic pathway that occurs on a single potential energy surface described within the Born-Oppenheimer approximation. A second pathway opens microseconds into the reaction as a portion of the reacting population competitively transitions from triplet to singlet multiplicity to circumvent energetic barriers on the triplet surface. These pathways are single- and two-state reactive (SSR and TSR) where the Co+ cation mediates an oxidative addition/reductive elimination sequence of the CH3CHO molecule. The third observed reaction pathway is the aldehyde hydrogen tunneling through an Eyring barrier to form high-spin products. First-order rate constants for the adiabatic and nonadiabatic energy lowered pathways, and the hydrogen tunneling pathway, are each measured using the single photon initiated dissociative rearrangement reaction (SPIDRR) experimental technique. We believe that this is the first experimental study where such disparate dynamic features (SSR, TSR, and H-tunneling) are disentangled in a system's chemistry, attributing specific rate constant values to each effect and quantifying the various competitions. Moreover, multi-reference CASSCF/CASPT2 calculations indicate that structures with covalent Co-H bonds are present exclusively along the excited singlet surface. This phenomenon significantly reduces these structures' energy relative to their triplet counterparts, thus enabling the surface crossing and spin inversion that cause the observed two-state reactivity.


Molecular screening of the proopiomelanocortin (POMC ) gene in Italian obese children: report of three new mutations.
Although linkage studies strongly suggest that proopiomelanocortin (POMC) alterations could play a role in the genetic predisposition to obesity, systematic POMC mutational analysis did not completely confirm this hypothesis. To verify the presence of mutations of the POMC coding region in Italian children with very early onset obesity. Eighty seven unrelated Italian obese children and adolescents were studied. Mean age at obesity onset was 4.7+/-2.5 y. The POMC gene coding region was screened using single-strand conformation polymorphism (SSCP) analysis. Bi-directional automatic sequencing of PCR products was performed for all individuals who showed an aberrant SSCP pattern. Three new mutations have been identified in the heterozygous state in three patients: (a) G3834C, resulting in the substitution of Ser with Thr at codon 7 within the POMC signal peptide; (b) C3840T, resulting in the substitution of Ser with Leu at codon 9 of the pre-proopiomelanocortin signal peptide; and (c) C7406G, producing the substitution of Arg with Gly at codon 236 within the beta-endorphin peptide. A polymorphism consisting of a 9 bp insertion, AGC AGC CGC, between position 6997 and 6998 has been found at the heterozygous state in nine patients. They showed leptin levels adjusted for BMI, gender and pubertal stage significantly higher than obese subjects homozyous for the POMC wild-type allele. Mutations in codons 7 and 9 of the signal peptide may alter the translocation of the pre-proopiomelanocortin into the endoplasmic reticulum and, therefore, can be implicated in obesity. Although further studies are required, the polymorphism between position 6997 and 6998 may represent one of the genetic variations that explain the linkage between obesity and POMC. International Journal of Obesity (2001) 25, 61-67