[RT-PCR-based methods for identification and typing of infectious hemopoietic necrosis virus in salmons].
A RT-PCR method has been developed to diagnose infectious hemopoietic necrosis virus (IHNV) in salmons. The authors show it possible to use the method for viral shedding in both a cell culture and a clinical sample from infected fishes. Genotyping of IHNV strains originating from North America, Europe, and Russia, by using the restriction fragment length polymerase analysis, has revealed that 10 of them belong to 3 existing genogroups (U, M, and L). Three Russian isolates are assigned into a separate subgroup. Phylogenetic analysis of several isolates has confirmed that viral strains from Katchatka belong to the North American U-genogroup whereas 3 Russian isolates from the continental zone of the country make up a separate subgroup within the same genogroup.


Autoimmune effector cells. I. Transfer of experimental encephalomyelitis with lymphoid cells cultured with antigen.
Relatively low numbers of spleen and lymph node cells from Lewis rats previously challenged with myelin basic protein efficiently transfer experimental allergic encephalomyelitis (EAE) to normal syngeneic recipients after in vitro culture with antigen. Moreover, cells obtained from rats that have recovered and are resistant to EAE can also transfer disease. Cell separation studies show that a nylon wool-adherent cell is responsible for transfer of EAE. Density gradient ultracentrifugation revealed that these effector cells are probably lymphoblasts.


Universal Health Care: The Cost of Being Human.
In this article I argue that the biological processes that make us human have error rates that distribute illness on a no-fault basis. I propose this as an ethical foundation for universal healthcare.


Prevalence of psychiatric diagnoses in children with mental retardation: data from a population-based study.
The main purpose of the study was to estimate the prevalence of psychiatric diagnoses in children with mental retardation (MR) (IQ < or = 70). All children born between 1980 and 1985 (N=30037) in Akershus County, Norway, were screened for possible MR and assessed with either IQ tests or standardized developmental tests. A total of 178 children, 79 with severe mental retardation (SMR) (IQ<50) and 99 with mild mental retardation (MMR) (IQ 50 to 70) were included for further study. Psychiatric symptomatology was assessed as a standard part of the neurodevelopmental examination, which included a semistructured parent interview, a clinical child interview, and retrieval of the charts of previous child psychiatric examinations. Psychiatric diagnoses were classified according to the International Classification of Disease (ICD-10). In total, 65 (37%) of the total population with MR (95% confidence intervals 29 to 44) were registered to have psychiatric diagnoses, the most common being hyperkinesia (n=28) and pervasive developmental disorder (n=15). Psychiatric diagnoses were present in 42% of the population with SMR and 33% of the population with MMR (p=0.4). Of all children found to have a psychiatric diagnosis, approximately one-third had previously been examined by a child psychiatrist and indicated a previously unrecognized need for these services to children with MR.


Are emotionally driven and addictive-like eating behaviors the missing links between psychological distress and greater body weight?
There is now a large body of evidence suggesting a significant association between emotional discomfort management, disordered eating behaviors and weight status. In the field of overweight and obesity, emotionally driven eating habits that resemble addictive behaviors are considered as a risk factor. This study aimed to investigate in a large sample of French university students 1) the associations between self-reported levels of psychological distress (PD), emotional eating (EE), food addiction (FA) and Body Mass Index (BMI); and 2) the potential mediation effect of eating behaviors (EE and FA) between PD and BMI. The responses of 1051 students (76.3% females) to self-reports assessing PD (Perceived Stress Scale, Hospital Anxiety and Depression Scale), EE (Intuitive Eating Scale-2) and FA (modified Yale Food Addiction Scale) were analysed. Associations between variables (Spearman correlation) and group comparisons by sex and BMI categories (Student's t tests/ANOVA) were tested, followed by Structural Equation Modeling (SEM) by sex. Among females and males, EE and FA scores were positively inter-related and correlated with PD scores and BMI. Moreover, among females and males, SEM showed that both EE and FA acts as mediators between PD and BMI. Hence, among educated young adults, using food consumption for down-regulating negative mood places the individual at risk for overweight and obesity. This study further emphasizes the necessity to take into account emotionally driven and addictive-like eating behaviors in interventions for promoting healthy eating and weight management.


Immunology of the gut: role of the eosinophil.
The gut wall is one of the conspicuous sites of eosinophil accumulation, presumably because of local chemotactic stimuli. It is reasonable to assume that one chemotactic factor is released by the mast cell, which is often found in proximity to the eosinophil. The association of eosinophils and eosinophilia with allergic disorders has long been recognized, and recent work has shown that increased eosinophil production is mediated by the lymphocyte. That process shares characteristics with other immunological actions. An increased rate of eosinophil tissue accumulation and destruction may be the factor which initiates the mechanism for increased production. None of many hypotheses about the 'function' of the eosinophil is substantiated; nevertheless it seems likely that this member of the immunological apparatus, which tends to be distributed in the front line (mucosal and cutaneous tissues), fulfils some normal protective or homeostatic function. Aside from that assumed normal function, there is growing clinical evidence that eosinophils can at times cause host injury, for example in such states as eosinophilic gastroenteritis and endomyocarditis.


The pulmonary pathology of COVID-19.
A growing number of international postmortem studies identify acute and organizing diffuse alveolar damage (DAD) as the main pathologic feature of lung injury in patients with COVID-19. Other forms of acute lung injury, including organizing pneumonia, and acute fibrinous and organizing pneumonia are seen. Acute neutrophilic infiltrates have been observed, most frequently as the manifestation of a superimposed bacterial pneumonia. SARS-CoV-2 has been detected in type I and type II pneumocytes and bronchial epithelial cells using electron microscopy, immunohistochemistry, and in situ hybridization, and likewise, viral transcripts were localized with RNA probes in pneumocytes. However, the presence of true viral cytopathic effect seen with light microscopy remains to be defined. Interestingly, vascular changes are frequently observed in association with DAD, which include severe endothelial injury/endothelialitis, hemorrhage, and thrombotic and microangiopathic vasculopathy. Since similar vascular changes also occur in cases of DAD independent of the etiology, whether the vascular pathology in COVID lungs has unique features and represents a separate pathologic process is under investigation.


A noninternalized nondesensitized truncated AT1A receptor transduces an amplified ANG II signal.
The structural determinants of the rat angiotensin (ANG) II AT1A receptor involved in receptor internalization, desensitization, and activation are investigated by producing six mutants that had progressively larger deletions of the cytoplasmic tail (-13, -19, -24, -31, -46, and -56 residues, respectively). After stable transfection of the cDNAs into Chinese hamster ovary cells, all mutants, except the most truncated, exhibit normal [Sar1]ANG II affinities [dissociation constant (Kd) = 0.19-0.70 nM] compared with the wild-type (WT) receptor (Kd = 0.62 nM) and are able to activate a Gq/11 protein and a phospholipase C as measured by the ANG II-induced inositol phosphate (IP) turnover in the different clones. However, one of these mutants, delta 329 (deletion of 31 residues), exhibits a peculiar phenotype. This mutant shows a reduced ligand-induced internalization as measured by the acid-washing procedure (only 32% of receptors are internalized vs. 83% for WT). Moreover, the delta 329 mutant is less desensitized by a pretreatment with either ANG II (15% desensitization of ANG II-stimulated IP turnover vs. 60% for WT receptor) or the phorbol ester phorbol 12-myristate 13-acetate (no desensitization vs. 29% for WT receptor). These functional modifications of the delta 329 mutant are associated with the transduction of an amplified signal as demonstrated on both IP turnover and an integrated physiological effect of ANG II. Taken together, these data indicate that the sequence 329SLSTKMS335 of the rat AT1A receptor is involved in both receptor internalization and desensitization. This is the first demonstration that a desensitization- and internalization-defective AT1A receptor mutant is also hyperreactive and mediates augmented cellular responses.


Health impact assessment of liquid biofuel production.
Bioethanol and biodiesel as potential substitutes for fossil fuels in the transportation sector have been analyzed for environmental suitability. However, there could be impacts on human health during the production, therefore adverse health effects have to be analyzed. The aim of this study is to analyze to what health risk factors humans are exposed to in the production of biofuels and what the size of the health effects is. A health impact assessment expressed as disability adjusted life years (DALYs) was conducted in SimaPro 7.1 software. The results show a statistically significant lower carcinogenic impact of biofuels (p < 0.05) than fossil fuels. Meanwhile, the impact of organic respirable compounds is smaller for fossil fuels (p < 0.05) than for biofuels. Analysis of inorganic compounds like PM₁₀,₂.₅, SO₂ or NO(x) shows some advantages of sugar beet bioethanol and soybean biodiesel production (p < 0.05), although production of sugarcane bioethanol shows larger impacts of respirable inorganic compounds than for fossil fuels (p < 0.001). Although liquid biofuels are made of renewable energy sources, this does not necessary mean that they do not represent any health hazards.


Interpretable Autoencoders Trained on Single Cell Sequencing Data Can Transfer Directly to Data from Unseen Tissues.
Autoencoders have been used to model single-cell mRNA-sequencing data with the purpose of denoising, visualization, data simulation, and dimensionality reduction. We, and others, have shown that autoencoders can be explainable models and interpreted in terms of biology. Here, we show that such autoencoders can generalize to the extent that they can transfer directly without additional training. In practice, we can extract biological modules, denoise, and classify data correctly from an autoencoder that was trained on a different dataset and with different cells (a foreign model). We deconvoluted the biological signal encoded in the bottleneck layer of scRNA-models using saliency maps and mapped salient features to biological pathways. Biological concepts could be associated with specific nodes and interpreted in relation to biological pathways. Even in this unsupervised framework, with no prior information about cell types or labels, the specific biological pathways deduced from the model were in line with findings in previous research. It was hypothesized that autoencoders could learn and represent meaningful biology; here, we show with a systematic experiment that this is true and even transcends the training data. This means that carefully trained autoencoders can be used to assist the interpretation of new unseen data.


Inhibition of leucocyte motility and prevention of immune-complex experimental colitis by hydroxychloroquine.
The inhibitory effects of hydroxychloroquine on leucocyte motility have been compared with those of prednisolone. It has been shown to have similar potency to prednisolone as an inhibitor of human neutrophil and monocyte motility. Hydroxychloroquine has then been compared with placebo in the prevention of an immune-complex experimental colitis in rabbits. Rectal biopsies were taken from rabbits 24 hours after initiation of colitis, coded, and graded histologically. The summated gradings for acute inflammation and goblet cell depletion had worsened more in the control rabbits (mean grade +6.7) than in the treated rabbits (mean grade +1.8) P less than 0.05. There was no difference in the mononuclear cell infiltrate between the two groups. Hydroxychloroquine, which is a potent inhibitor of leucocyte motility, effectively prevents the acute inflammatory infiltrate in this experimental colitis model and therefore merits trial in human ulcerative colitis.


Network Management System for IoT Based on Dynamic Systems.
The Internet of Things (IoT) has the potential to transform the public sector by combining the leading technical and business trends of mobility, automation, and data analysis to dramatically alter the way public bodies collect data and information. Embedded sensors, actuators, and other devices that capture and transmit information about network activity in real-time are used in the Internet of Things to connect networks of physical objects. The design of a network management system for an IoT network is presented in this paper, which uses the edge computing model. This design is based on the Internet management model, which uses the SNMP protocol to communicate between managed devices, and a gateway, which uses the SOAP protocol to communicate with a management application. This work allowed for the identification and analysis of the primary network management system initiatives for IoT networks, in which there are four fundamental device management requirements for any deployment of IoT devices: provisioning and authentication, configuration and control, monitoring and diagnostics, and software updates and maintenance.


Trends in palatine tonsillar cancer incidence and mortality rates in the United States.
The purpose of this paper is to describe the extent of the public health problem presented by palatine tonsillar cancer in the United States by analyzing recent incidence and mortality rate trends. Using the National Cancer Institutes' Surveillance, Epidemiology and End Results (SEER) Program database, age-adjusted incidence rates (1973-2001) for five histological types of palatine tonsillar cancer by race and sex were calculated. For total palatine tonsillar cancer age-specific incidence (1973-2001) and mortality (1969-2001) rates by race and sex were calculated. Mortality and population data were obtained from the National Center for Health Statistics (NCHS) and the U.S. Census Bureau. The Joinpoint Regression Model was employed to establish the statistical significance of incidence and mortality rate trends. The majority of palatine tonsillar cases diagnosed in SEER-9 registries from 1973 to 2001 occurred among white males, age 40-64 years, with squamous cell carcinoma (SCC). The highest incidence of palatine tonsillar cancer occurred in black males, followed by white males with SCC. For age 40-64 years, palatine tonsillar incidence rates significantly declined for white females and black females, rose and then declined for black males, but increased from 1988 for white males. For age 65+ years, incidence significantly declined among white males. Palatine tonsillar cancer mortality rates for age 40-64 years significantly declined for white females. Rates also declined for black females (1981-2001) and black males (1985-2001) in this age group while rates for white males declined significantly from 1969 to 1987, but stabilized at nearly 0.4 through 2001. Mortality for the age group, 65+, significantly rose and fell for white females and declined for white males. Beginning in the late 1980s, and continuing through 2001, the risk for white males, age 40-64 years, of developing palatine tonsillar cancer increased. In contrast, the risk for white males, age 65 years and older, of developing palatine tonsillar cancer and of dying from this disease decreased during the study period.


Functional mapping of rbOCT1 and rbOCT2 activity in the S2 segment of rabbit proximal tubule.
A strategy was developed to determine the distribution of activity mediated by the organic cation (OC) transporters OCT1 and OCT2 in rabbit renal proximal tubule (RPT). Both transporters displayed similar affinities for tetraethylammonium (TEA; in CHO-K1 cells, TEA concentrations that resulted in half-maximal transport were 19.9 and 34.5 microM for OCT1 and OCT2, respectively). Similarly, some OCs showed little capacity to discriminate between the two processes (IC50 values for ephedrine of 13.6 and 24.2 microM for OCT1 and OCT2, respectively). However, OCT2 had a higher affinity for cimetidine and [2-(4-nitro-2,1,3-benzoxadiazol-7-yl) aminoethyl]trimethylammonium (NBD-TMA; 1.3 and 1.4 microM, respectively) than did OCT1 (97.3 and 108 microM, respectively). Conversely, OCT1 had a higher affinity for tyramine and pindolol than did OCT2 (21.2 and 2.4 vs. 361 and 50 microM, respectively). We designated these as "discriminatory inhibitors" and used them to determine the relative contribution of OCT1 and OCT2 for TEA transport in single S2 segments of rabbit RPT. Cimetidine and NBD-TMA were high-affinity inhibitors of TEA transport in S2 segments (median IC50 values of 12.3 and 1.4 microM, respectively); in comparison, tyramine and pindolol were low-affinity inhibitors (265 and 69.3 microM, respectively). These IC50 values were sufficiently close to those for OCT2 to support the conclusion that TEA transport in the S2 segment of rabbit RPT is dominated by OCT2. However, the profile of inhibition of tyramine (an OCT1-selective substrate) transport in single S2 segments indicated that, despite a comparatively low level of expression, OCT1 can play a dominant role in the uptake of selected OC substrates.


Reliability and validity of a questionnaire for self-assessment of complete dentures.
Demand for complete denture treatment is expected to rise over several decades. However, to date, no questionnaire on complete dentures, as evaluated by edentulous patients, has been shown to be reliable and valid. This study sought to assess the reliability and validity of Patient's Denture Assessment (PDA), which provides a multidimensional evaluation of dentures among edentulous patients. Patients, who had new complete dentures fabricated at the University Hospital of Dentistry, Tokyo Medical and Dental University through 2009 to 2010, were enrolled. The reliability of the PDA was determined by examining internal consistency and test-retest reliability. Internal consistency for all of the question items and the six subscales was measured using Cronbach's α and average inter-item correlation coefficients among 93 participants. For 33 of these participants, test-retest reliability was determined at a 2 month-interval using the interclass correlation coefficients (ICCs) and 95% confidence interval for the summary scores and the six subscale scores. The PDA was validated in 93 participants by examining the difference in the summary score and the six subscale scores of the PDA before and after replacement with new dentures by the paired t-test. Ability to detect change was also tested in 93 patients using effect size. The Cronbach's α for the PDA ranged from 0.56 to 0.93. The average inter-item correlation coefficients ranged from 0.28 to 0.83. ICCs for the PDA ranged from 0.37 to 0.83. The paired t-test showed a significant difference between the summary score and the six subscale scores before and after replacement with new dentures (p < 0.05) and the effect size was 0.97. The PDA demonstrated good reliability by assessing internal consistency and test-retest reliability. In addition, the PDA demonstrated good validity by assessing discriminant validity. Thus, the PDA could help dentists obtain a detailed understanding of the patients' perceptions in using their dentures.


Evaluating hematuria in adults.
Although most causes of hematuria are benign, urinary tract bleeding may signal the existence of a life-threatening disease. Gross and microscopic hematuria share a common differential diagnosis, including urinary tract infection, urolithiasis and bladder cancer. Clinical evaluation may be guided by the patient's age, sex, medical history and physical examination. Intravenous pyelography or sonography is usually the first procedure performed, although cystoscopy is indicated in the face of active bleeding. Those patients who remain undiagnosed after a complete evaluation should be followed with routine urinalysis and cytology to allow early detection of malignancy.


Emergence and persistence of CXCR4-tropic HIV-1 in a population of men from the multicenter AIDS cohort study.
We examined the emergence of CXCR4 (i.e., X4) tropism in 67 male human immunodeficiency virus type 1 (HIV-1) seroconverters from the Multicenter AIDS Cohort Study (MACS) who were selected to reflect the full spectrum of rates of HIV-1 disease progression. A mean of 10 serial samples per donor were evaluated by a laboratory-validated, commercially available assay to determine phenotypic coreceptor use. A total of 52% of men had dual- or mixed-tropic HIV-1 detected at 1 or more of the time points tested. Use of X4 by HIV-1 was detected more frequently among men who developed AIDS (defined as a CD4(+) T cell count of <200 cells/muL and/or an AIDS-defining illness) < or =11 years after seroconversion than among those who did not (P = .005), as well as among men who exhibited a total T cell count decline (i.e., a CD3(+) inflection point), compared with those who did not (P = .03). For men in whom both X4 virus and an inflection point were detected, emergence of X4 virus preceded the inflection point by a median of 0.83 years. The median CD4(+) T cell count at first detection of X4 viruses before the onset of AIDS was 475 cells/microL. We conclude that HIV-1 variants that used X4 frequently emerged at high CD4(+) T cell counts and may contribute to the decrease in T cell numbers during late HIV-1 infection.


Polyphenol Metabolite Pyrogallol-O-Sulfate Decreases Microglial Activation and VEGF in Retinal Pigment Epithelium Cells and Diabetic Mouse Retina.
(Poly)phenol-derived metabolites are small molecules resulting from (poly)phenol metabolization after ingestion that can be found in circulation. In the last decade, studies on the impact of (poly)phenol properties in health and cellular metabolism accumulated evidence that (poly)phenols are beneficial against human diseases. Diabetic retinopathy (DR) is characterized by inflammation and neovascularization and targeting these is of therapeutic interest. We aimed to study the effect of pyrogallol-O-sulfate (Pyr-s) metabolite in the expression of proteins involved in retinal glial activation, neovascularization, and glucose transport. The expression of PEDF, VEGF, and GLUT-1 were analyzed upon pyrogallol-O-sulfate treatment in RPE cells under high glucose and hypoxia. To test its effect on a diabetic mouse model, Ins2Akita mice were subjected to a single intraocular injection of the metabolite and the expression of PEDF, VEGF, GLUT-1, Iba1, or GFAP measured in the neural retina and/or retinal pigment epithelium (RPE), two weeks after treatment. We observed a significant decrease in the expression of pro-angiogenic VEGF in RPE cells. Moreover, pyrogallol-O-sulfate significantly decreased the expression of microglial marker Iba1 in the diabetic retina at different stages of disease progression. These results highlight the potential pyrogallol-O-sulfate metabolite as a preventive approach towards DR progression, targeting molecules involved in both inflammation and neovascularization.


Prostaglandins, arachidonic acid, and inflammation.
The enzymatic oxidation of arachidonic acid has been shown to yield potent pathological agents by two major pathways. Those of the prostaglandin (PG) pathway, particularly PGE2, have been implicated as inflammatory mediators for many years. The discovery and biological activities of thromboxane A2 and prostacyclin as well as a destructive oxygen-centered radical as additional products of this biosynthetic pathway now require these to be considered as potential inflammatory mediators. Like PGE2, their biosynthesis is prevented by nonsteroidal anti-inflammatory agents. More recently, the alternative metabolic route, the lipoxygenase pathway, has been shown to yield a new class of arachidonic acid oxygenation products, called the leukotrienes, which also appear to be important inflammatory mediators. Unlike the prostaglandins, some of which play important roles as biological regulators, the actions of the lipoxygenase products appear to be exclusively of a pathological nature.


Human left atrial appendage anatomy and overview of its clinical significance.
The left atrial appendage (LAA) is an important anatomic region since it is a source of thromboembolism in patients with atrial fibrillation. Although this anatomic and clinical relation it has received little attention until recent years. This descriptive laboratory study was performed in 56 hearts of adult formalin fixed cadavers. The morphological characteristics of LAA were recorded. The distances between the orifices of left superior pulmonary veins (LSPV), circumflex artery, left anterior descending (LAD) artery, mitral valve and LAA were also measured in this study. The morphological appearance of the LAA was classified into two different ways. There were two types according to the first classification: slender like a crooked finger (in 73.2%) and stump-like (in 26.8%). The lobe number of LAA was two in 64.3% specimens and three in 35.7%. The types of LAA were Cactus (24%), Chicken Wing (12%), Windsock (38%) and Cauliflower (26%) according to the second classification. The LAA orifice was oval-shaped in 37.5% and round-shaped in 62.5%. The bridge on the orifice was determined in one specimen. The longest diameter of LAA orifice was 16.5±4 mm. The presence of accessory left atrial appendage was observed in one specimen. The distance between LAA orifice and oval fossa was 27.5±5.5 mm. We highlighted the anatomic features of LAA and LAA orifice. LAA diameters, shape and the relation between neighboring structures in relation to atrial fibrillation and surgical approaches were discussed.


Cardiac involvement of major thalassemia and evaluation of total serum creatine kinase and creatine kinase-mB isoenzyme and cardiac troponinI in these patients.
The goal of this study was the evaluation of specific markers of myocardial injury that includes CK-MB and troponin I in major thalassemic patients. Regular blood transfusion is the main treatment in major thalassemia. One of the most important complications of regular blood transfusion is iron overload that eventually involves many organs like heart and cause myocardial injury. Sixty patients with transfusion-dependent major thalassemia, at the age range of 8 to 15 years in Tabriz Pediatric Medical Center were chosen. Measurement of Hb, Hct and serum ferritin were performed in hospital laboratory, but total serum Creatine Kinase (CK) by photometric and isoenzyme of CK-MB by immunologic DGKC and cardiac troponin I (cTnI) were tested by ELISA methods in Shaheed Madani heart center laboratory before blood transfusion. For all patients echocardiography and ECG assessment of cardiac function were done by a pediatric cardiologist and results were statistically analyzed. Forty nine patients (group A) had normal left ventricular ejection fraction (LVEF = 50-70%) and 11 patients (group B) had reduced LVEF (20-45%). There was no statistical difference between two groups in average volume of blood transfusion (p = 0.074). Although total CK and CK-MB isoenzyme were higher in group B but there was no statistically meaningful difference between two groups (p = 0.123, p = 0.111). Troponin I also was higher in group B but statistically analysis showed no correlation between cardiac function and troponin I level in these groups (p = 0.827). This study showed that cardiac markers are not helpful for recognition of cardiac involvement in major thalassemia.


Prehistoric tuberculosis in america: adding comments to a literature review.
Tuberculosis is a prehistoric American human disease. This paper reviews the literature and discusses hypotheses for origins and epidemiological patterns of prehistoric tuberculosis. From the last decades, 24 papers about prehistoric tuberculosis were published and 133 cases were reviewed. In South America most are isolated case studies, contrary to North America where more skeletal series were analyzed. Disease was usually located at the deserts of Chile and Peru, Central Plains in USA, and Lake Ontario in Canada. Skeletal remains represent most of the cases, but 16 mummies have also been described. Thirty individuals had lung disease, 19 of them diagnosed by the ribs. More then 100 individuals had osseous tuberculosis and 26 also had it in other organs. As today, transmission of the infection and establishment of the disease were favored by cultural and life-style changes such as sedentarization, crowding, undernutrition, use of dark and insulated houses, and by the frequency of interpersonal contacts. The papers confirm that despite previous perceptions, tuberculosis seems to have occurred in America for millennia. It only had epidemiological expression when special conditions favored its expansion. Occurring as epidemic bursts or low endemic disease, it had differential impact on groups or social segments in America for at least two millennia.


Supra-treatment threshold neonatal jaundice: Incidence in HIV-exposed compared to non-exposed neonates at Queen Elizabeth Central Hospital in Blantyre, Malawi.
Jaundice is the yellowish pigmentation of the skin, sclera, and mucous membranes resulting from bilirubin deposition. Children born to mothers with HIV are more likely to be born premature, with low birth weight, and to become septic-all risk factors for neonatal jaundice. Further, there has been a change in the prevention of mother-to-child transmission (PMTCT) of HIV guidelines from single-dose nevirapine to a six-week course, all of which theoretically put HIV-exposed newborns at greater risk of developing neonatal jaundice. We carried out a study to determine the incidence of severe and clinical neonatal jaundice in HIV-exposed neonates admitted to the Chatinkha Nursery (CN) neonatal unit at Queen Elizabeth Central Hospital (QECH) in Blantyre. Over a period of four weeks, the incidence among non-exposed neonates was also determined for comparison between the two groups of infants. Clinical jaundice was defined as transcutaneous bilirubin levels greater than 5 mg/dL and severe jaundice as bilirubin levels above the age-specific treatment threshold according the QECH guidelines. Case notes of babies admitted were retrieved and information on birth date, gestational age, birth weight, HIV status of mother, type of feeding, mode of delivery, VDRL status of mother, serum bilirubin, duration of stay in CN, and outcome were extracted. Of the 149 neonates who were recruited, 17 (11.4%) were HIV-exposed. One (5.88%) of the 17 HIV-exposed and 19 (14.4%) of 132 HIV-non-exposed infants developed severe jaundice requiring therapeutic intervention (p = 0.378). Eight (47%) of the HIV-exposed and 107 (81%) of the non-exposed neonates had clinical jaundice of bilirubin levels greater than 5 mg/dL (p < 0.001). The study showed a significant difference in the incidence of clinical jaundice between the HIV-exposed and HIV-non-exposed neonates. Contrary to our hypothesis, however, the incidence was greater in HIV-non-exposed than in HIV-exposed infants.


Allergen-induced histaminergic and non-histaminergic activation of itch C-fiber nerve terminals in mouse skin.
Acute cutaneous exposure to allergen often leads to itch, but seldom pain. The effect of mast cell activation on cutaneous C-fibers was studied using innervated isolated mouse skin preparation that allows for intra-arterial delivery of chemicals to the nerve terminals in the skin. Allergen (ovalbumin) injection into the isolated skin of actively sensitized mice strongly stimulated chloroquine (CQ)-sensitive C-fibers (also referred to as "itch" nerves); on the other hand, CQ-insensitive C-fibers were activated only modestly, if at all. The histamine H1 receptor antagonist pyrilamine abolished itch C-fibers response to histamine, but failed to significantly reduce the response to ovalbumin. Ovalbumin also strongly activated itch C-fibers in skin isolated from Mrgpr-cluster Δ-/- mice. When pyrilamine was studied in the Mrgpr-cluster Δ-/- mice thereby eliminating the influence of both histamine H1 and Mrgpr receptors (MrgprA3 and C11 are selectively expressed by itch nerves), the ovalbumin response was very nearly eliminated. The data indicate that the acute activation of itch C-fibers in mouse skin is largely secondary to the combined effect of activation of histamine H1 and Mrpgr receptors.


Clinically derived dose effect relationship for hyperthermia given in combination with low dose radiotherapy.
A group of 36 patients, treated on 44 fields with fractionated treatments of local high-frequency induced hyperthermia and radiotherapy to the low total dose of 14-25 Gy, was retrospectively evaluated for differences between responders (i.e., complete and partial responders) and non-responders. A response rate of 86% was achieved, comprising 14% (6/44) complete and 73% (32/44) partial response. There was an indication that the probability of complete response is greater in smaller tumours. The tumour temperatures achieved were higher in the responders than in the non-responders. Logistic analysis was performed on the mean temperature achieved. This temperature parameter yielded a significant positive dose-effect relationship with regard to therapeutic effect, from which a 50% effective dose of 38.8 degrees C was calculated. The data indicate that to obtain the maximum therapeutic effect, i.e., greater than 95% response rate, tumour temperatures above 42.5 degrees C need to be achieved.


Green fluorescent protein and its derivatives as versatile markers for gene expression in living Drosophila melanogaster, plant and mammalian cells.
We have investigated the utility of the green fluorescent protein (GFP) as a marker for gene expression in living adult Drosophila melanogaster (Dm) and cultured plant and mammalian cells. Using Dm, we generated transgenic flies bearing a glass-responsive gfp fusion gene to test the utility of GFP as a spatial reporter. In the adult living fly, GFP is clearly visible in the ocelli and the eye. We have optimized the use of filters for distinguishing the GFP signal from abundant autofluorescence in living Dm. In addition, we have used GFP to identify photoreceptor cells in pupal eye cultures that have been fixed and stained according to standard histological procedures. GFP was also detected in individual living plant cells following transient transfection of soybean suspension cultures, demonstrating that GFP is an effective transformation marker in plant cells. Similarly, transient transfection of mammalian cells with a modified form of GFP, S65T, allowed detection of single living cells expressing the reporter. This modified form of GFP gave a robust signal that was resistant to photobleaching. We then used a CellScan system exhaustive photon reassignment (EPR) deconvolution algorithm to generate high-resolution three-dimensional images of GFP fluorescence in the living cell.


Effects of exercise and weight loss in older adults with obstructive sleep apnea.
Obstructive sleep apnea (OSA) is prevalent among older individuals and is linked to increased cardiovascular disease morbidity. This study examined the change in OSA severity after exercise training and dietary-induced weight loss in older adults and the association of the changes in OSA severity, body composition, and aerobic capacity with arterial distensibility. Obese adults (n = 25) with OSA, age 60 yr or older, were instructed to participate in supervised exercise (3 d·wk) and follow a calorie-restricted diet. Baseline assessments of OSA parameters, body weight and composition, aerobic capacity, and arterial distensibility were repeated at 12 wk. Nineteen participants completed the intervention. At 12 wk, there were reductions in body weight (-9%) and percentage of total body fat (-5%) and trunk fat (-8%) whereas aerobic capacity improved by 20% (all P < 0.01). The apnea-hypopnea index decreased by 10 events per hour (P < 0.01) and nocturnal SaO2 (mean SaO2) improved from 94.9% at baseline to 95.2% after intervention (P = 0.01). Arterial distensibility for the group was not different from that at baseline (P = 0.99), yet individual changes in distensibility were associated with the change in nocturnal desaturations (r = -0.49, P = 0.03) but not with the change in body weight, apnea-hypopnea index, or aerobic capacity. The severity of OSA was reduced after an exercise and weight loss program among older adults, suggesting that this lifestyle approach may be an effective first-line nonsurgical and nonpharmacological treatment for older patients with OSA.


Feasibility study of lesion classification via contrast-agent-aided UWB breast imaging.
This letter investigates the feasibility of applying contrast agents for lesion classification in ultra wideband (UWB) breast imaging. Previous study has focused on distinguishing benign from malignant masses by exploiting their morphology-dependent backscatter signature via the complex natural resonances of the late-time target response. The tissue differentiation capability, however, deteriorates severely if the intrinsic contrast between the dielectric properties of dysplastic and normal tissues are small. A possible solution to this problem is proposed in this letter via the use of microwave contrast agents, where the damping factors of the differential backscatter responses before and after the infusion of contrast agents to a dysplastic inclusion are used to correlate with the anomaly shapes. The feasibility of this approach for lesion classification is demonstrated through comprehensive simulation studies using realistic numerical breast models.


Salmeterol in the treatment of chronic asthma.
Salmeterol is a highly selective beta 2-adrenoreceptor agonist with a long duration of action--as long as 12 hours or more. When inhaled twice daily in the management of chronic asthma, salmeterol can improve lung function and the quality of life for patients with asthma, and reduce acute asthma exacerbations. It is also a useful adjunct in the treatment of exercise-induced asthma and nocturnal asthma. In patients who continue to have symptomatic asthma despite the regular use of an inhaled corticosteroid, salmeterol acts as a secondary controller of symptoms and reduces the need for inhaled short-acting beta 2-agonist "rescues". Since salmeterol is different from other beta 2 agonists, patients must be carefully educated in its proper use. Salmeterol should be administered in combination with an inhaled anti-inflammatory medication as adjunctive therapy, but it should not be used for rescue bronchodilatation.


[Immunocytochemical study of the myoepithelial cells in fibrocystic disease and ductal carcinoma of the breast].
Myoepithelial cells (MC) were identified and the pattern of their distribution in dysplasia and duct carcinoma of the mammary gland was studied using a monospecific antiserum to smooth-muscle myosin of the human uterus, by the indirect Coons' method under luminescent microscope. Samples of the operation material from 10 patients with fibrous-cystic mastopathy and 26 patients with duct carcinoma were examined. In solid (7 observations) and comedo (4 observations) carcinomas with the structure of cancer in situ, MC were found intact in the periphery. In invasive growth of these tumors as well as in scirrhus (5 observations) and adenocarcinoma (10 observations) MC disappeared from the duct structures and were absent in carcinoma proliferates. Positive immunofluorescence in the conventional location of MC in the alveolar duct system of the mammary gland allows sufficiently valid identification and study of the distribution and changes in these cells. The immunocytochemical verification of MC in dysplasia and duct carcinoma indicates the possibility of using MC as markers of duct carcinoma in situ; MC disappearance from the duct structures characterizes the beginning of the infiltrative tumor growth.


Central Mechanisms of Itch.
This chapter summarizes recent findings regarding the central transmission of acute and chronic itch. Itch is transduced by cutaneous pruriceptors that transmit signals to neurons in the superficial spinal cord. Spinal itch-signaling circuits utilize several neuropeptides whose receptors represent novel targets to block itch transmission. Itch is relieved by scratching, which activates spinal interneurons to inhibit itch-transmitting neurons. Spinal itch transmission is also thought to be modulated by descending pathways. Itch is transmitted rostrally via ascending pathways to activate a variety of brain regions involved in sensory discrimination of affective and motor responses to itch. The pathophysiological mechanisms of chronic itch are poorly understood but likely involve sensitization of itch-signaling pathways and/or dysfunction of itch-inhibitory circuits. Improved understanding of central itch mechanisms has identified a number of novel targets for the development of antipruritic treatment strategies.


Chlorophyll catabolism in senescing plant tissues: In vivo breakdown intermediates suggest different degradative pathways for Citrus fruit and parsley leaves.
High-pressure liquid chromatography was used to separate chlorophyll derivatives in acetone extracts from senescing Citrus fruit peel, autumnal Melia azedarach L. leaves, and dark-held detached parsley (Petroselinum sativum L.) leaves. Chlorophyllide a and another polar, dephytylated derivative accumulated in large amounts in senescing Citrus peel, particularly in fruit treated with ethylene. Ethylene also induced a 4-fold increase in the specific activity of Citrus chlorophyllase (chlorophyll chlorophyllidohydrolase, EC 126.96.36.199). Detailed kinetics based on a hexane/acetone solvent partition system showed that the in vivo increase in dephytylated derivatives coincided with the decrease in total chlorophyll. Polar, dephytylated derivatives accumulated also in senescing Melia leaves. Senescing parsley leaves revealed a very different picture. The gradual disappearance of chlorophyll a was accompanied by an increase in pheophytin a and by the transient appearance of several phytylated derivatives. Only pheophytin a and an adjacent peak were left when all the chlorophyll a had disappeared. The pathways for breakdown of chlorophyll in the Citrus and parsley senescence systems are discussed.


IDE Degrades Nociceptin/Orphanin FQ through an Insulin Regulated Mechanism.
Insulin-degrading enzyme (IDE) was applied to catalyze hydrolysis of Nociceptin/Orphanin 1-16 (OFQ/N) to show the involvement of the enzyme in degradation of neuropeptides engaged in pain transmission. Moreover, IDE degradative action towards insulin (Ins) was inhibited by the OFQ/N fragments, suggesting a possible regulatory mechanism in the central nervous system. It has been found that OFQ/N and Ins affect each other degradation by IDE, although in a different manner. Indeed, while the digestion of OFQ/N is significantly affected by the presence of Ins, the kinetic profile of the Ins hydrolysis is not affected by the presence of OFQ/N. However, the main hydrolytic fragments of OFQ/N produced by IDE exert inhibitory activity towards the IDE-mediated Ins degradation. Here, we present the results indicating that, besides Ins, IDE cleaves neuropeptides and their released fragments act as inhibitors of IDE activity toward Ins. Having in mind that IDE is present in the brain, which also contains Ins receptors, it cannot be excluded that this enzyme indirectly participates in neural communication of pain signals and that neuropeptides involved in pain transmission may contribute to the regulation of IDE activity. Finally, preliminary results on the metabolism of OFQ/N, carried out in the rat spinal cord homogenate in the presence of various inhibitors specific for different classes of proteases, show that OFQ/N proteolysis in rat spinal cord could be due, besides IDE, also to a cysteine protease not yet identified.


Exhaled nitric oxide in acute respiratory syncytial virus bronchiolitis.
To investigate fractional exhaled nitric oxide (FeNO) levels in infants during acute respiratory syncytial virus (RSV) bronchiolitis and during convalescence. Prospective cohort study. Comparison of FeNO levels between infants with laboratory-confirmed acute RSV bronchiolitis and 2 control groups: healthy infants and infants with recurrent wheezing. The Department of Pediatric Emergency Medicine and the Pediatric Pulmonary Clinic of the Tel Aviv Medical Center from November 2008 to July 2009. The FeNO levels were measured at referral and at 2 visits over 4 months after convalescence. The FeNO level was measured using the multiple-breath exhalation technique. Forty-four infants with acute RSV bronchiolitis (mean [SD] age, 6.8 [7.3] months), 21 infants with recurrent wheezing (mean [SD] age, 10.8 [7.59] months), and 32 age-matched healthy controls (mean [SD] age, 6.8 [9.1] months). Follow-up data were available for 22 children (55%) for the first follow-up visit and for 11 children (25%) for the second follow-up visit. Acute RSV bronchiolitis. The FeNO levels during acute RSV bronchiolitis vs controls and FeNO levels during follow-up vs acute-stage disease. Mean FeNO levels for RSV-positive infants were significantly lower compared with healthy controls and infants with recurrent wheezing: mean (SD), 1.89 (1.76) parts per billion (ppb), 7.28 (4.96) ppb, and 4.86 (7.49) ppb, respectively (P<.001). The FeNO levels at the 2- and 4-month follow-up visits increased to 7.74 (5.13) ppb and 11.37 (6.29) ppb, respectively (P=.001). The FeNO levels are temporarily reduced during acute RSV bronchiolitis and increase during convalescence to normal levels and higher. The mechanisms for this suppression and its relation to future wheezing and asthma need to be studied.


Rapid determination of cell mass and density using digitally controlled electric field in a microfluidic chip.
The density of a single cell is a fundamental property of cells. Cells in the same cycle phase have similar volume, but the differences in their mass and density could elucidate each cell's physiological state. Here we report a novel technique to rapidly measure the density and mass of a single cell using an optically induced electrokinetics (OEK) microfluidic platform. Presently, single cellular mass and density measurement devices require a complicated fabrication process and their output is not scalable, i.e., it is extremely difficult to measure the mass and density of a large quantity of cells rapidly. The technique reported here operates on a principle combining sedimentation theory, computer vision, and microparticle manipulation techniques in an OEK microfluidic platform. We will show in this paper that this technique enables the measurement of single-cell volume, density, and mass rapidly and accurately in a repeatable manner. The technique is also scalable - it allows simultaneous measurement of volume, density, and mass of multiple cells. Essentially, a simple time-controlled projected light pattern is used to illuminate the selected area on the OEK microfluidic chip that contains cells to lift the cells to a particular height above the chip's surface. Then, the cells are allowed to "free fall" to the chip's surface, with competing buoyancy, gravitational, and fluidic drag forces acting on the cells. By using a computer vision algorithm to accurately track the motion of the cells and then relate the cells' motion trajectory to sedimentation theory, the volume, mass, and density of each cell can be rapidly determined. A theoretical model of micro-sized spheres settling towards an infinite plane in a microfluidic environment is first derived and validated experimentally using standard micropolystyrene beads to demonstrate the viability and accuracy of this new technique. Next, we show that the yeast cell volume, mass, and density could be rapidly determined using this technology, with results comparable to those using the existing method suspended microchannel resonator.


Herpes simplex virus type-selective enzyme-linked immunosorbent assay with Helix pomatia lectin-purified antigens.
Helix pomatia lectin-purified antigens with specific reactivity to herpes simplex virus type 1 (HSV-1) and HSV-2 antibodies in human sera were used in an enzyme-linked immunosorbent assay. The type specificity of the antigens was assessed by double immunodiffusion precipitation in gel against rabbit HSV-1 and HSV-2 hyperimmune sera, and by enzyme-linked immunosorbent assay with human reference sera containing antibodies to either type of HSV. Fifty-two sera from patients with documented infection with either HSV-1 or HSV-2 were assayed for HSV type-specific immunoglobulin G antibodies. The reactivity of the sera against lectin-purified antigens correlated completely with the results of virus typing. We conclude that HSV type-specific immunoglobulin G antibodies can easily be measured by enzyme-linked immunosorbent assay with the use of Helix pomatia lectin-purified HSV-1 and HSV-2 antigens.


Laparoscopic hysterectomy for benign indications: clinical practice guideline.
Since the introduction of minimally invasive gynecologic surgery, the percentage of advanced laparoscopic procedures has greatly increased worldwide. It seems therefore, timely to standardize laparoscopic gynecologic care according to the principles of evidence-based medicine. With this goal in mind-the Dutch Society of Gynecological Endoscopic Surgery initiated in The Netherlands the development of a national guideline for laparoscopic hysterectomy (LH). This present article provides a summary of the main recommendations of the guideline. This guideline was developed following the Dutch guideline of medical specialists and in accordance with the AGREE II tool. Clinically important issues were firstly defined and translated into research questions. A literature search per topic was then conducted to identify relevant articles. The quality of the evidence of these articles was rated following the GRADE systematic. An expert panel consisting of 18 selected gynecologists was consulted to formulate best practice recommendations for each topic. Ten topics were considered in this guideline, including amongst others, the different approaches for hysterectomy, advice regarding tissue extraction, pre-operative medical treatment and prevention of ureter injury. This work resulted in the development of a clinical practical guideline of LH with evidence- and expert-based recommendations. The guideline is currently being implemented in The Netherlands. A guideline for LH was developed. It gives an overview of best clinical practice recommendations. It serves to standardize care, provides guidance for daily practice and aims to guarantee the quality of LH at an (inter)national level.


Eculizumab Maintenance and the Prevention of Atypical Hemolytic Uremic Syndrome Relapse During Pregnancy: A Case Report.
Atypical hemolytic uremic syndrome is a thrombotic microangiopathy that can cause life-threatening anemia, thrombocytopenia, and acute renal failure. When triggered during pregnancy or the acute postpartum period, the disease is referred to as pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS). Women who suffer P-aHUS may later want to consider future pregnancy. These patients are at high, though not well-estimated, risk of relapse. Eculizumab, a monoclonal antibody against complement 5 (C5), has been highly successful in treating acute attacks of P-aHUS, but little is known about the effectiveness of eculizumab maintenance therapy throughout pregnancy. In this case report, we present a woman whose first pregnancy was complicated by severe P-aHUS. In her next pregnancy, she was maintained on eculizumab. She delivered a healthy infant at term and had no recurrences of P-aHUS during the pregnancy or in the postpartum period.


Changes in reward contingency modulate the trial-to-trial variability of hippocampal place cells.
Pyramidal cells in the rodent hippocampus often exhibit clear spatial tuning. Theories of hippocampal function suggest that these "place cells" implement multiple, independent neural representations of position (maps), based on different reference frames or environmental features. Consistent with the "multiple maps" theory, previous studies have shown that manipulating spatial factors related to task performance modulates the within-session variability (overdispersion) of cells in the hippocampus. However, the influence of changes in reward contingency on overdispersion has not been examined. To test this, we first trained rats to collect food from three feeders positioned around a circular track (task(1)). When subjects were proficient, the reward contingency was altered such that every other feeder delivered food (task(2)). We recorded ensembles of hippocampal neurons as rats performed both tasks. Place cell overdispersion was high during task(1) but decreased significantly during task(2), and this increased reliability could not be accounted for by changes in running speed or familiarity with the task. Intuitively, decreased variability might be expected to improve neural representations of position. To test this, we used Bayesian decoding of hippocampal spike trains to estimate subjects' location. Neither the amount of probability decoded to subjects' position (local probability) nor the difference between estimated position and true location (decoding accuracy) differed between tasks. However, we found that hippocampal ensembles were significantly more self-consistent during task(2) performance. These results suggest that changes in task demands can affect the firing statistics of hippocampal neurons, leading to changes in the properties of decoded neural representations.


Internalization and fate of Escherichia coli O157:H7 in leafy green phyllosphere tissue using various spray conditions.
In the past decade, leafy greens have been implicated in several outbreaks of foodborne illness, and research has focused on contamination during preharvest operations. Concerns have been raised that internalization of pathogens into the edible tissue occurs where postharvest chemical interventions would be ineffective. This study was initiated to measure the degree and fate of Escherichia coli O157:H7 internalized in the phyllosphere tissue of leafy greens when spray conditions, inoculum level, and type of leafy green were varied. Two spraying treatments were applied: (i) spraying individual spinach or lettuce leaves on plants once with a high dose (7 to 8 log CFU/ml) of E. coli O157:H7 and (ii) spraying spinach, lettuce, or parsley plants repeatedly (once per minute) with a low dose (2.7 to 4.2 log CFU/ml) of E. coli O157:H7 over a 10- to 20-min period. With the high-dose spray protocol, no significant differences in the prevalence of internalization occurred between Shiga toxin-negative E. coli O157:H7 isolates and virulent isolates (P > 0.05), implying that the Shiga toxin virulence factors did not influence internalization or the subsequent fate of those populations under these test conditions. Significantly greater internalization of E. coli O157:H7 occurred in spinach leaves compared with lettuce leaves when leaves were sprayed once with the high-dose inoculum (P < 0.05), whereas internalization was not observed in lettuce leaves but continued to be observed in spinach and parsley leaves following repeated spraying of the low-dose inoculum. Based on these results, it is surmised that a moisture film was generated when spraying was repeated and this film assisted in the mobilization of pathogen cells to plant apertures, such as stomata. E. coli O157:H7 cells that were internalized into spinach tissue using a low-dose repeat-spray protocol were temporary residents because they were not detected 2 days later, suggesting that plant-microbe interactions may be responsible.


Complexity and significance in computer simulations of physiological systems.
Complexity in a theoretical model may or may not be associated with a high level of arbitrariness, depending on how the model is constructed. In this paper I use examples from cardiac electrophysiology to illustrate two techniques for maintaining significance in complex simulations. First, the approaches of analysis and synthesis are compared as methods of constructing models of complex systems. When a model is constructed by synthesis of known principles, facts, and subunits, it may have any degree of complexity without losing significance; the same is not true for analysis models. Significance can also be maintained by assembling a limited model to test a specific hypothesis of mechanism.


A redescription of Myxobolus inornatus from young-of-the-year smallmouth bass (Micropterus dolomieu).
During investigations of young-of-the year smallmouth bass ( Micropterus dolomieu ) mortalities in the Susquehanna River, Pennsylvania, U.S.A. and affected tributaries, raised areas were noted in the muscle in the vicinity of the caudal peduncle. The raised areas were caused by plasmodia of a myxozoan parasite. Spores found within plasmodia were similar to those of Myxobolus inornatus previously described from the caudal peduncle of fingerling largemouth bass ( Micropterus salmoides ) in Montana. Here, M. inornatus is redescribed based on histologic comparisons and spore measurements. The addition of spore photographs, line drawings, a voucher specimen, and partial small-subunit ribosomal (rSSU) DNA gene sequence are new in this study. This is also the first description of M. inornatus from smallmouth bass. The plasmodia of M. inornatus were grossly observed at the base of the caudal and dorsal fins and were 280.3 ± 33.5 (range 77.1-920.3) μm long and 320.6 ± 41.0 (range 74.85-898.4) μm wide. In some instances, plasmodia of M. inornatus were large enough to rupture the epidermis or were associated with misaligned vertebrae. The slightly pyriform spores were 11.3 ± 0.2 (range 8.6-17.4) μm in length and 8.6 ± 0.2 (range 7.1-13.7) μm wide with an iodinophilous vacuole and a sutural ridge with 8 to 10 sutural folds. The SSU rDNA gene sequence places M. inornatus in a sister group with Myxobolus osburni .


Pediatric Patient with Ischemic Stroke: Initial Approach and Early Management.
Acute Ischemic Stroke (AIS) in children is an acute neurologic emergency associated with significant morbidity and mortality. Although the incidence of AIS in pediatric patients is considerably lower than in adults, the overall cumulative negative impact of the quality of life could be even higher in children. The age-related variable clinical presentation could result in a delay in diagnosis and could negatively influence the overall outcome. The early management should be based on early recognition, acute transfer to pediatric AIS centre, standardised approach (ABCDE), early neurologic examination together with neuroimaging (preferable Magnetic Resonance Imaging-MRI). The treatment is based on supportive therapy (normoxemia, normocapnia, normotension and normoglycemia) in combination with intravenous/intraarterial thrombolytic therapy and/or mechanical thrombectomy in selected cases. Pediatric stroke centres, together with the implementation of local stroke management protocols, could further improve the outcome of pediatric patients with AIS.


Changes in leaf cuticular waxes of sesame (Sesamum indicum L.) plants exposed to water deficit.
Sesame (Sesamum indicum L.) is one of the most important oilseed crops, having seeds and oil that are highly valued as a traditional health food. The objective of this study was to evaluate leaf cuticular wax constituents across a diverse selection of sesame cultivars, and the responses of these waxes to drought-induced wilting. Water-deficit was imposed on 18 sesame cultivars by withholding irrigation for 15d during the post-flowering stage, and the effect on seed yield and leaf waxes compared with a well-watered control. Leaf cuticular waxes were dominated by alkanes (59% of total wax), with aldehydes being the next-most abundant class. Compared to well-irrigated plants, drought treatment caused an increase in wax amount on most cultivars, with only three cultivars having a notable reduction. When expressed as an average across all cultivars, drought treatment caused a 30% increase in total wax amount, with a 34% increase in total alkanes, a 13% increase in aldehydes, and a 28% increase in the total of unknowns. In all cultivars, the major alkane constituents were the C27, C29, C31, C33, and C35 homologs, whereas the major aldehydes were the C30, C32, and C34 homologs, and drought exposure had only minor effects on the chain length distribution within these and other wax classes. Drought treatments caused a large decrease in seed yield per plant, but did not affect the mean weight of individual seeds, showing that sesame responds to post-flowering drought by reducing seed numbers, but not seed size. Seed yield was inversely correlated with the total wax amount (-0.466*), indicating that drought induction of leaf wax deposition does not contribute directly to seed set. Further studies are needed to elucidate the ecological role for induction of the alkane metabolic pathway by drought in regulating sesame plant survival and seed development in water-limiting environments.


Continuing Education Offering: Clinical Assessment of Symptom-Focused Health-Related Quality of Life in HIV/AIDS.
The routine clinical evaluation of health-related quality of life (HRQOL) improves quality of care in patients with HIV/AIDS by effectively assessing and optimizing treatment outcomes, enhancing patient adherence, improving communication between patients and clinicians/nurses, and documenting changes in patients' health status over time. Existing HRQOL assessment tools may not be appropriate for this purpose, as they are designed for clinical trials and research, and exclude several aspects relevant to QOL in patients with HIV/AIDS in the clinical setting. Therefore, there is a need for a new, user-friendly, HIV-specific clinical assessment tool that briefly but effectively evaluates symptom-related HRQOL issues most relevant to patients with HIV/AIDS, including fatigue, depression, pain, nausea and vomiting, sleep disturbances, sexual dysfunction, and body image changes. This article describes the role of nurses in HRQOL assessment in HIV/AIDS, compares commonly used assessment tools, and evaluates the applicability of these tools for routine clinical use in this patient population.


Adsorption of RNA on mineral surfaces and mineral precipitates.
The prebiotic significance of laboratory experiments that study the interactions between oligomeric RNA and mineral species is difficult to know. Natural exemplars of specific minerals can differ widely depending on their provenance. While laboratory-generated samples of synthetic minerals can have controlled compositions, they are often viewed as "unnatural". Here, we show how trends in the interaction of RNA with natural mineral specimens, synthetic mineral specimens, and co-precipitated pairs of synthetic minerals, can make a persuasive case that the observed interactions reflect the composition of the minerals themselves, rather than their being simply examples of large molecules associating nonspecifically with large surfaces. Using this approach, we have discovered Periodic Table trends in the binding of oligomeric RNA to alkaline earth carbonate minerals and alkaline earth sulfate minerals, where those trends are the same when measured in natural and synthetic minerals. They are also validated by comparison of co-precipitated synthetic minerals. We also show differential binding of RNA to polymorphic forms of calcium carbonate, and the stabilization of bound RNA on aragonite. These have relevance to the prebiotic stabilization of RNA, where such carbonate minerals are expected to have been abundant, as they appear to be today on Mars.


Lack of Evidence for Regional Brain Volume or Cortical Thickness Abnormalities in Youths at Clinical High Risk for Psychosis: Findings From the Longitudinal Youth at Risk Study.
There is cumulative evidence that young people in an "at-risk mental state" (ARMS) for psychosis show structural brain abnormalities in frontolimbic areas, comparable to, but less extensive than those reported in established schizophrenia. However, most available data come from ARMS samples from Australia, Europe, and North America while large studies from other populations are missing. We conducted a structural brain magnetic resonance imaging study from a relatively large sample of 69 ARMS individuals and 32 matched healthy controls (HC) recruited from Singapore as part of the Longitudinal Youth At-Risk Study (LYRIKS). We used 2 complementary approaches: a voxel-based morphometry and a surface-based morphometry analysis to extract regional gray and white matter volumes (GMV and WMV) and cortical thickness (CT). At the whole-brain level, we did not find any statistically significant difference between ARMS and HC groups concerning total GMV and WMV or regional GMV, WMV, and CT. The additional comparison of 2 regions of interest, hippocampal, and ventricular volumes, did not return any significant difference either. Several characteristics of the LYRIKS sample like Asian origins or the absence of current illicit drug use could explain, alone or in conjunction, the negative findings and suggest that there may be no dramatic volumetric or CT abnormalities in ARMS.


Copper chelators: chemical properties and bio-medical applications.
Copper is present in different concentrations and chemical forms throughout the earth crust, surface and deep water and even, in trace amounts, in the atmosphere itself. Copper is one of the first metals used by humans, the first artifacts dating back 10,000 years ago. Currently, the world production of refined copper exceeds 16,000 tons/year. Copper is a micro-element essential to life, principally for its red-ox properties that make it a necessary cofactor for many enzymes, like cytochrome-c oxidase and superoxide dismutase. In some animal species (e.g. octopus, snails, spiders, oysters) copper-hemocyanins also act as carriers of oxygen instead of hemoglobin. However, these red-ox properties also make the pair Cu(+)/Cu(2+) a formidable catalyst for the formation of reactive oxygen species, when copper is present in excess in the body or in tissues. The treatment of choice in cases of copper overloading or intoxication is the chelation therapy. Different molecules are already in clinical use as chelators or under study or clinical trial. It is worth noting that chelation therapy has also been suggested to treat some neurodegenerative diseases or cardiovascular disorders. In this review, after a brief description of the homeostasis and some cases of dyshomeostasis of copper, the main (used or potential) chelators are described; their properties in solution, even in relation to the presence of metal or ligand competitors, under physiological conditions, are discussed. The legislation of the most important Western countries, regarding both the use of chelating agents and the limits of copper in foods, drugs and cosmetics, is also outlined.


Effect of Axial Eye Length on Retinal Vessel Parameters in 6 to 12-Year-Old Malay Girls.
Retinal vessel analysis is affected by both systemic and ocular factors. Malays are the major ethnicity in South East Asia. Data on the retinal microvasculature in Malays is limited, especially among children. We aim to evaluate the influence of ocular biometry on retinal vessel parameters in young Malay girls. This was a cross-sectional, hospital-based study involving 86 Malay girls aged 6 to 12 years old in Hospital Universiti Sains Malaysia from 2015-2016. Ocular examination, refraction, biometry, retinal photography, and anthropometric measurements were performed. The central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE) and overall fractal dimension (Df) were measured using validated computer-based methods (Singapore I vessel analyzer, SIVA version 3.0, Singapore). The associations of ocular biometry and CRAE, CRVE and Df were analyzed using multivariable analysis. The mean CRAE, CRVE and Df in Malay girls were 171.40 (14.40) um, 248.02 (16.95) um and 1.42 (0.05) respectively. Each 1 mm increase in axial length was associated with a reduction of 4.25 um in the CRAE (p = 0.03) and a reduction of 0.02 in the Df (p = 0.02), after adjustment for age, blood pressure and body mass index. No association was observed between axial length and CRVE. Anterior chamber depth and corneal curvature had no association with CRAE, CRVE or Df. Axial length affects retinal vessel measurements. Narrower retinal arterioles and reduced retinal fractal dimension were observed in Malay girls with longer axial lengths.


[Derivative allergens as predictors of allergic predisposition in next generations].
Through studding of statistical data was performed the analysis of allergosis sickness rate in Georgia during the last ten years (1998-2004) and was determined the steady rise of allergic illnesses with prevailing bronchial asthma in allergology. Were searched the main reasons for development of allergic illnesses and risk factors that provide formation of allergic disposition among the children, the parents of which were examined and treated in Allergology Clinic of Tbilisi State Medical University in 2004-2005. Among 535 examined adults ill with allergosis 2/5 were ill with bronchial asthma, 20% - with drug allergy, 13% - food-borne allergy, 11% - allergic dermatitis; the group of patients sick with insectallergy appeared the minimum - 1,5%. Among the allergens caused development of allergy is home dust, drug and food-borne allergens. Was determined the significant role of work contact with occupational allergens of patients in formation of allergic diseases among the children: correlative coefficient PR made 2,03 in 95% interval confidence within 1,36 - 3,09. Among the occupational allergens the chemical allergens were predominated (pesticides, synthetic detergents, drugs, dyestuff and dissolvent) - at about 75% from the total number of "guilty" allergens.


Sedentary Behavior and Light Physical Activity Are Associated with Brachial and Central Blood Pressure in Hypertensive Patients.
Physical activity is recommended as a part of a comprehensive lifestyle approach in the treatment of hypertension, but there is a lack of data about the relationship between different intensities of physical activity and cardiovascular parameters in hypertensive patients. The purpose of this study was to investigate the association between the time spent in physical activities of different intensities and blood pressure levels, arterial stiffness and autonomic modulation in hypertensive patients. In this cross-sectional study, 87 hypertensive patients (57.5 ± 9.9 years of age) had their physical activity assessed over a 7 day period using an accelerometer and the time spent in sedentary activities, light physical activities, moderate physical activities and moderate-to-vigorous physical activities was obtained. The primary outcomes were brachial and central blood pressure. Arterial stiffness parameters (augmentation index and pulse wave velocity) and cardiac autonomic modulation (sympathetic and parasympathetic modulation in the heart) were also obtained as secondary outcomes. Sedentary activities and light physical activities were positively and inversely associated, respectively, with brachial systolic (r = 0.56; P < 0.01), central systolic (r = 0.51; P < 0.05), brachial diastolic (r = 0.45; P < 0.01) and central diastolic (r = 0.42; P < 0.05) blood pressures, after adjustment for sex, age, trunk fat, number of antihypertensive drugs, accelerometer wear time and moderate-to-vigorous physical activities. Arterial stiffness parameters and cardiac autonomic modulation were not associated with the time spent in sedentary activities and in light physical activities (P > 0.05). Lower time spent in sedentary activities and higher time spent in light physical activities are associated with lower blood pressure, without affecting arterial stiffness and cardiac autonomic modulation in hypertensive patients.


Black, Asian and minority ethnic female nurses: colonialism, power and racism.
The history of black, Asian and minority ethnic (BAME) women who came to the UK to work as nurses is interwoven with the history of the NHS. The colonial construct of the BAME female nurse is embedded in British society. From the post-second-world-war years to the 1960s, to today, BAME women chose to become nurses and work in the 'motherland', a term regularly used by those immigrating to England from the former colonies. The experiences of the BAME female nurse in the 1970s and early 1980s were of overt racism and lack of advancement. Although racism was less overt in the late 1980s and 1990s, these experiences continued and BAME female nurse advancement levels remained lower than among their white female counterparts. In the 21st century there continues to be significant differences in treatment of BAME female nurses compared with white nursing colleagues, with the enduring effects of the coloniser holding the power to impact on the BAME female nurse who is the colonised, racially stereotyped and less powerful. There are multifaceted reasons for the unequal treatment of BAME female nurses. However, the persistent construct of colonialism and power needs to be recognised if the NHS is to acknowledge ongoing racialised inequalities experienced by BAME female nurses. A recognition of racist and sexist discriminatory actions must occur to permit the development of equal opportunity strategies to address these unacceptable inequalities and generate a real cultural shift.


Mrp4 confers resistance to topotecan and protects the brain from chemotherapy.
The role of the multidrug resistance protein MRP4/ABCC4 in vivo remains undefined. To explore this role, we generated Mrp4-deficient mice. Unexpectedly, these mice showed enhanced accumulation of the anticancer agent topotecan in brain tissue and cerebrospinal fluid (CSF). Further studies demonstrated that topotecan was an Mrp4 substrate and that cells overexpressing Mrp4 were resistant to its cytotoxic effects. We then used new antibodies to discover that Mrp4 is unique among the anionic ATP-dependent transporters in its dual localization at the basolateral membrane of the choroid plexus epithelium and in the apical membrane of the endothelial cells of the brain capillaries. Microdialysis sampling of ventricular CSF demonstrated that localization of Mrp4 at the choroid epithelium is integral to its function in limiting drug penetration into the CSF. The topotecan resistance of cells overexpressing Mrp4 and the polarized expression of Mrp4 in the choroid plexus and brain capillary endothelial cells indicate that Mrp4 has a dual role in protecting the brain from cytotoxins and suggest that the therapeutic efficacy of central nervous system-directed drugs that are Mrp4 substrates may be improved by developing Mrp4 inhibitors.


[Specialized medical service for polytrauma in a large city].
On the basis of studying of trauma epidemiolgy in a large city, principles of optimal organization of specialized medical service for patients with polytrauma have been developed. Urgent specialized service and further treatment of patients with this pathology should be fulfilled in a special department organized on the basis of a multi-profile hospital. The center of this department represents a specialized unit for patients with multiple and combined traumas supplied with all necessary specialists and means required for the management of this difficult group of patients.


[Adsorption of Vi antigen on human erythrocytes].
The accumulation of Vi-antigen in the human body was studied with the use of such characteristic as the specific adsorption capacity of red blood cells. This parameter was shown to depend on the phenotype in the ABO blood group system. In cases of typhoid fever an increase in the adsorption capacity of red blood cells was observed at the acute period of the disease. These changes were particularly manifest in patients belonging to groups O and A. The authors suggest that the adsorption of the antigen on red blood cells has a definite kinetics related to the dynamics of the infectious process.


Defining and Developing a Global Public Health Course for Public Health Graduates.
Global public health is increasingly being seen as a speciality field within the university education of public health. However, the exact meaning of global public health is still unclear, resulting in varied curricula and teaching units among universities. The contextual differences between high- and low- and middle-income countries, and the process of globalization need to be taken into account while developing any global public health course. Global public health and public health are not separable and global public health often appears as an extension of public health in the era of globalization and interdependence. Though global public health is readily understood as health of global population, it is mainly practiced as health problems and their solutions set within low- and middle-income countries. Additional specialist competencies relevant to the context of low- and middle-income countries are needed to work in this field. Although there can be a long list of competencies relevant to this broad topic, available literature suggests that knowledge and skills related with ethics and vulnerable groups/issues; globalization and its impact on health; disease burden; culture, society, and politics; and management are important.


Catching a resurgence: Increase in SARS-CoV-2 viral RNA identified in wastewater 48 h before COVID-19 clinical tests and 96 h before hospitalizations.
Curtailing the Spring 2020 COVID-19 surge required sweeping and stringent interventions by governments across the world. Wastewater-based COVID-19 epidemiology programs have been initiated in many countries to provide public health agencies with a complementary disease tracking metric and non-discriminating surveillance tool. However, their efficacy in prospectively capturing resurgences following a period of low prevalence is unclear. In this study, the SARS-CoV-2 viral signal was measured in primary clarified sludge harvested every two days at the City of Ottawa's water resource recovery facility during the summer of 2020, when clinical testing recorded daily percent positivity below 1%. In late July, increases of >400% in normalized SARS-CoV-2 RNA signal in wastewater were identified 48 h prior to reported >300% increases in positive cases that were retrospectively attributed to community-acquired infections. During this resurgence period, SARS-CoV-2 RNA signal in wastewater preceded the reported >160% increase in community hospitalizations by approximately 96 h. This study supports wastewater-based COVID-19 surveillance of populations in augmenting the efficacy of diagnostic testing, which can suffer from sampling biases or timely reporting as in the case of hospitalization census.


Resonance coupling and polarization conversion in terahertz metasurfaces with twisted split-ring resonator pairs.
We investigate edge-coupling of twisted split-ring resonator (SRR) pairs in the terahertz (THz) frequency range. Using a simple coupled-resonator model we show that such a system exhibits resonance splitting and cross-polarization conversion. Numerical simulations and experimental measurements agree well with theoretical calculations, verifying the resonance splitting as a function of the coupling strength given by the SRR separation. We further show that a metal ground plane can be integrated to significantly enhance the resonance coupling, which enables the effective control of resonance splitting and the efficiency and bandwidth of the cross-polarization conversion. Our findings improve the fundamental understanding of metamaterials with a view of accomplishing metamaterial functionalities with enhanced performance, which is of great interest in realizing THz functional devices required in a variety of applications.


Bacterial infections in a pediatric cohort of primary and acquired complement deficiencies.
Acquired complement deficiency can occur in the setting of autoimmune syndromes, such as systemic lupus erythematosus (SLE), with very low or, occasionally, undetectable C3 levels. Based on inherited complement defects, patients with transiently low complement may be at similar risk for serious bacterial infection, but the degree of risk related to C3 level and temporal association is unknown. We performed a retrospective study including pediatric patients with undetectable total complement activity or absent individual complement components measured at our institution from 2002 to 2018. We assessed annual rate of serious bacterial infection (SBI) defined as requiring hospitalization and/or parenteral antibiotics by manual chart review. Among included SLE patients, we assessed the 30-day probability of SBI for given C3 measurements using a logistic regression model to determine risk. Primary complement deficiency was analyzed for SBI rate as comparison. Covariates included age, level of immune suppression and history of lupus nephritis. Acquired complement deficiency secondary to SLE-related disease [n = 44] was the most common underlying diagnosis associated with depressed complement levels and were compared to a cohort of primary complement deficient patients [n = 18]. SBI per 100 person-years and cohort demographics were described in parallel. Our logistic regression analysis of pediatric patients with SLE showed low C3 level was temporally associated with having an SBI event. Given equivalent immunosuppression, patients with an SBI had lower C3 levels at the beginning of the observation period relative to patients without SBI. Pediatric patients with the diagnosis of SLE can develop very low C3 levels that associate with risk of serious bacterial infection comparable to that of patients with primary complement deficiency. Patients prone to severe complement consumption may particularly be at risk.


[Biosynthesis of 5- methoxy-N-acetyltryptamine (melatonin) in enterochromaffin cells].
Chromatographic analysis of the alkaline extract of the gastrointestinal mucosa of rabbits rich in enterochromaffin cells displayed the presence of melatonin (5-methoxy-N-acetyltryptamine) and its precursors (5-oxytryptophane, tryptamine, serotonine, mexamine) in it. Detection of precursors indicated that not a passive accumulation, but an active synthesis of melatonin occurred in the enterochromaffin cells. Epiphysis was not the only place of melatonin synthesis. Functional condition of enterochromaffin cells was largely determined by the extent of physiological and pathological reactions of the organism.


Localization of the candidate genes ELOVL5 and SCD1 for 'male effect' pheromone synthesis in goats (Capra hircus).
The 'male effect' is a well-known phenomenon in female sheep and goats, whereby pheromone-induced activation of reproductive function occurs. In a previous study, we showed that the genes for elongation of long-chain fatty acids family member 5 (ELOVL5) and stearoyl-CoA desaturase 1 (SCD1) increased their expression significantly, concomitant with induction of pheromone synthesis. Therefore, these genes were considered to be prime candidate genes for pheromone synthesis. In the present study, we performed in situ hybridization to investigate where these two genes are expressed in goat skin. Strong positive signals were detected for both genes in the head skin of the male goat, which is the main site of pheromone production, and were mainly in the basal layer of the sebaceous gland cells, with the remaining cells showing negligible signals. None of the cells in the rump skin of the male goat or the head skin of the orchidectomized goat, neither of which produce pheromone, exhibited strong positive signals. The present study demonstrates that expression of these two candidate genes for pheromone synthesis is primarily localized in the sebaceous glands of the pheromone-producing skin region.


Ethylene Oxide Gas Sterilization of Medical Devices.
Ethylene oxide gas is an agent in the sterilization of medical devices due to its effectiveness and compatibility with most materials. The advantages and disadvantages, as well as its recommended uses, are explored in this review article. The variables and their relevance on process optimization are described, the types of processing cycles are detailed and emphasis is given to the design and validation of the sterilization process.


Meta-analysis of all immune epitope data in the Flavivirus genus: inventory of current immune epitope data status in the context of virus immunity and immunopathology.
A meta-analysis was performed in order to inventory the immune epitope data related to viruses in the genus Flavivirus. Nearly 2000 epitopes were captured from over 130 individual Flavivirus-related references identified from PubMed and reported as of September 2009. This report includes all epitope structures and associated immune reactivity from the past and current literature, including: the epitope distribution among pathogens and related strains, the epitope distribution among different pathogen antigens, the number of epitopes defined in human and animal models of disease, the relationship between epitopes identified in different disease states following natural (or experimental) infection, and data from studies focused on candidate vaccines. We found that the majority of epitopes were defined for dengue virus (DENV) and West Nile virus (WNV). The prominence of DENV and WNV data in the epitope literature is likely a reflection of their overall worldwide impact on human disease, and the lack of vaccines. Conversely, the relatively smaller number of epitopes defined for the other viruses within the genus (yellow fever and Japanese encephalitis virus) most likely reflects the presence of established prophylaxis and/or their more modest impact on morbidity and mortality globally. Through this work we hope to provide useful data to those working in the area of Flavivirus research.


[Behavior and evolution].
Main works of D.K. Belyaev on genetic and evolutionary aspects of behavior are reviewed. Principal trends in development of this problem in modern science are considered. The role of Darwinian evolution in formation of human and animal behavior and evolutionary significance of behavior are discussed.


Grain-growth Inhibitor with Three-section-sintering for Highly Dispersed Single-crystal NCM90 Cubes.
Single crystallization of LiNix Coy Mn1-x-y O2 (NCM) is currently an effective strategy to improve the cycling life of NCM cathode, owing to the reduced surface area and enhanced mechanical strength, but the application of single crystal NCM(SC-NCM) is being hindered by severe particle agglomeration and poor C-rate performance. Here, a strategy of three-section-sintering(TSS) with the presence of grain-growth inhibitor was proposed, in which, the TSS includes three sections of phase-formation, grain-growth and phase-preservation. While, the addition of MoO3 inhibits the grain growth and restrains the particle agglomeration. With the help of TSS and 1 mol % of MoO3 , highly dispersed surface Mo-doped SC-NCM(MSC-NCM) cubes are obtained with the average diameter of 1.3 μm. Benefiting from the surface Mo-doping and the reduced surface energy, the Li+ -migration preferred (1 0 4) crystalline facet is exposed as the dominant plane in MSC-NCM cubes, because of which, C-rate performance is significantly improved compared with the regular SC-NCM. Furthermore, this preparation strategy is compatible well with the current industrial production line, providing an easy way for the large-scale production of SC-NCM.


Utility of routine screening for alpha-1 antitrypsin deficiency in patients with bronchiectasis.
Alpha-1 antitrypsin deficiency (AATD) is a cause of bronchiectasis. Guidelines for bronchiectasis from the British Thoracic Society do not recommend to routinely test patients for AATD. In contrast, guidelines for AATD recommend routine screening. This contradiction, in part, results from the lack of data from large studies performing comprehensive screening. We screened 1600 patients with bronchiectasis at two centres in the UK from 2012 to 2016. In total, only eight individuals with AATD were identified representing 0.5% of the overall population. We conclude that routine screening for AATD in bronchiectasis in the UK has a low rate of detection. Further studies are required in different geographical regions, which may have a higher prevalence of AATD.


The Effects of Increased Body Temperature on Motor Control during Golf Putting.
This study investigated the effect of increased core temperature on the performance outcome and movement kinematics of elite golfers during a golf putting task. The study aimed to examine individual differences in the extent to which increased temperature influenced the rate of putting success, whether increased temperature speeded up the timing of the putting downswing and whether elite golfers changed their movement kinematics during times of thermal stress. Six participants performed 20 putts to each of four putt distances (1, 2, 3, and 4 m) under normal temperature conditions and when core body temperature was increased. There was no significant difference in the number of successful putts between the two temperature conditions, but there was an increase in putterhead velocity at ball impact on successful putts to distances of 1 and 4 m when temperature was elevated. This reflected an increase in swing amplitude rather than a reduction in swing duration as hypothesized. There were individual differences in the motor control response to thermal stress as three of the golfers changed the kinematic parameters used to scale their putting movements to achieve putts of different distances at elevated temperatures. Theoretical implications for these findings and the practical implications for elite golfers and future research are discussed.


Impact of Wooden Breast myopathy on in vitro protein digestibility, metabolomic profile, and cell cytotoxicity of cooked chicken breast meat.
This study investigated the impacts of Wooden Breast (WB) abnormality on in vitro protein digestibility and cytotoxicity of cooked chicken breast meat. Chicken breasts without (non-WB, n = 6) or with severe WB condition (WB, n = 6) were cooked and subjected to static in vitro protein digestion. The results showed no significant differences in free-NH2, degree of hydrolysis and distribution of peptide molecular weight between non-WB and WB samples at late intestinal digestion (P5), suggesting no adverse effects of WB on protein digestibility. Based on peptidomic analysis, P5 fraction of WB showed greater content of peptides with oxidative modification than that of non-WB. Untargeted metabolomics did not find any metabolites with potential toxicity either in non-WB and WB. Hydrolyzed non-WB and WB (1.56-100 µg/mL) did not affect viability of Caco-2 and Vero cells but addition of WB samples reduced Caco-2 cell viability compared with non-WB.


Primary hypogonadism and partial alopecia in three sibs with müllerian hypoplasia in the affected females.
We describe 3 sibs, two females and a male, with hypogonadism, defective Müllerian development in the sisters, and partial alopecia consisting of cranial hair only in the center of the scalp. One sister had absent gonads, the other had streak ovaries; both had markedly hypoplastic internal genitalia. Their brother had hormonal and histologic findings consistent with germinal cell aplasia. In view of the fact that the parents were consanguineous, autosomal recessive inheritance of the syndrome is likely.


Dose Escalated Radiation Therapy for Glioblastoma Multiforme: An International Systematic Review and Meta-Analysis of 22 Prospective Trials.
Limited evidence is available on the utility of dose-escalated radiation therapy (DE-RT) with or without temozolomide (TMZ) versus standard-of-care radiation therapy (SoC-RT) for patients with newly diagnosed glioblastoma multiforme. We performed a systematic review/meta-analysis to compare overall survival (OS) and progression-free survival (PFS) between DE-RT and SoC-RT. We used a Population, Intervention, Control, Outcomes, Study Design/Preferred Reporting Items for Systematic Reviews and Meta-analyses/Meta-analysis of Observational Studies in Epidemiology selection criterion to identify studies. The primary and secondary outcomes were 1-year OS and 1-year PFS, respectively. Outcomes and comparisons were subdivided based on receipt of TMZ and MGMT status. DE-RT was defined based on equivalent dose calculations. Random effects meta-analyses using the Knapp-Hartung correction, arcsine transformation, and restricted maximum likelihood method were conducted. Meta-regression was used to compare therapeutic (eg, DE-RT or TMZ) and pathologic characteristics (eg, MGMT methylation status) using the Wald-type test. Across 22 published studies, 2198 patients with glioblastoma multiforme were included; 507 received DE-RT. One-year OS after DE-RT alone was higher than SoC-RT alone (46.3% vs 23.4%; P = .02) as was 1-year PFS (17.9% vs 5.3%; P = .02). No significant difference in 1-year OS (73.2% vs 64.4%; P = .23) or 1-year PFS (44.5% vs 44.3%; P = .33) between DE-RT + TMZ and SoC-RT + TMZ was noted. No difference in 1-year OS was noted between DE-RT + TMZ and SoC-RT + TMZ in either MGMT methylated (83.2% vs 73.2%; P = .23) or MGMT unmethylated (72.6% vs 50.6%; P = .16) patients. DE-RT alone resulted in superior PFS and OS versus SoC-RT alone. DE-RT + TMZ did not lead to improved outcomes versus SoC-RT + TMZ. No differential benefit based on MGMT status was found. Future studies are warranted to define which subgroups benefit most from DE-RT.


Mandibular bone graft material for reconstruction of alveolar cleft defects: long-term results.
To analyze the long-term effect of mandibular bone as donor material in bone grafting of the alveolar process defect in patients with unilateral cleft lip and palate (UCLP), compared with iliac crest cancellous bone. During a 7-year period, 101 UCLP patients were bone grafted, 57 cases with iliac crest cancellous bone and 44 with mandibular symphyseal bone. The long-term results with an observation time of more than 4 years were analyzed with respect to marginal bone level and dental and gingival condition in the grafted area. Complications were recorded. The bone level in the grafted area was satisfactory in both groups. Impaction of cleft-side canines was found in 35% of the patients in both groups. Patients with agenesis of the cleft side lateral incisor had significantly more impacted canines, compared with patients with a cleft-side lateral situated in the lesser maxillary segment, probably due to the fact that the lateral incisors help in guiding the canine down through the grafted area. The number of complications was scarce, although both groups demonstrated some gingival retraction with a longer crown length at the cleft side central incisor. The findings of this study have changed our strategy in bone grafting. Timing of orthodontic treatment and bone grafting has been more varied depending on the position and presence of teeth in the cleft area. Bone grafting of the alveolar process is not just a local treatment of a bony defect, but in respect to the burden of treatment, bone grafting of the alveolar process has to be planned in accordance with orthodontic treatment and maxillofacial growth.


[Beriberi after esophagectomy].
A 55-years-old man with a history of alcoholism, hypertension and obesity was diagnosed of epidermoid carcinoma of the middle third portion of the esophagus. He was treated with two cycles of cytostatics with cisplatin and 5-fluorouracil. Due to his poor general health an inability to swallow solids and liquids, he received parenteral nutrition for 20 days using a commercial formula lacking in vitamins and minerals. During distal esophagectomy we observed a tendency to hypotension and severe metabolic acidosis that was unexplained by the hemodynamic profile and that persisted throughout the first 24 hours after surgery. Once these complications were corrected, he was weaned from mechanical ventilation and the following neurological signs were observed: temporal and spacial disorientation, aphasia, ophthalmoplegia with divergent strabismus and later conduction aphasia, amnesia and confabulation. Circulation was hyperdynamic, requiring inotropics and vasoconstrictors. Korsakoff syndrome secondary to Wernicke's encephalopathy was diagnosed, and the response to thiamine treatment was favorable. Beriberi can be found in hospitalized patients and the anesthesiologist may be involved in their perioperative care. Symptoms resolve easily with vitamin B1 treatment, which is ideally provided along with other hydrosoluble vitamins. Treatment should be prompt because delay leads to greater morbiomortality.