Quantitative measurement of contact area and electron transport across platinum nanocontacts for scanning probe microscopy and electrical nanodevices.
Conductive modes of atomic force microscopy are widely used to characterize the electronic properties of materials, and in such measurements, contact size is typically determined from current flow. Conversely, in nanodevice applications, the current flow is predicted from the estimated contact size. In both cases, it is very common to relate the contact size and current flow using well-established ballistic electron transport theory. Here we performed 19 electromechanical tests of platinum nanocontacts with in situ transmission electron microscopy to measure contact size and conductance. We also used molecular dynamics simulations of matched nanocontacts to investigate the nature of contact on the atomic scale. Together, these tests show that the ballistic transport equations under-predict the contact size by more than an order of magnitude. The measurements suggest that the low conductance of the contact cannot be explained by the scattering of electrons at defects nor by patchy contact due to surface roughness; instead, the lower-than-expected contact conductance is attributed to approximately a monolayer of insulating surface species on the platinum. Surprisingly, the low conductance persists throughout loading and even after significant sliding of the contact in vacuum. We apply tunneling theory and extract best-fit barrier parameters that describe the properties of this surface layer. The implications of this investigation are that electron transport in device-relevant platinum nanocontacts can be significantly limited by the presence and persistence of surface species, resulting in current flow that is better described by tunneling theory than ballistic electron transport, even for cleaned pure-platinum surfaces and even after loading and sliding in vacuum.


Erwinia uzenensis sp. nov., a novel pathogen that affects European pear trees (Pyrus communis L.).
Bacteria were isolated from black lesions on shoots of European pear trees (Pyrus communis L.) in an orchard in Japan. Previous characterization of this novel pathogen by phenotypic and genotypic methods suggested that it should belong to the genus Erwinia but might not correspond to either Erwinia amylovora or Erwinia pyrifoliae. Here, phylogenetic analyses of the 16S rRNA gene, gyrB, and rpoD gene sequences indicated that it could not be assigned to any recognized species of the genus Erwinia. DNA-DNA hybridization confirmed that the bacterial strains represented a novel species. The DNA G+C contents, the fatty acid profile and phenotypic characteristics resembled those previously reported for members of the genus Erwinia. On the basis of these and previous results, the pathogen represents a novel species of the genus Erwinia, for which the name Erwinia uzenensis sp. nov. (type strain: YPPS 951(T) = LMG 25843(T) = NCPPB 4475(T)) is proposed.


Polymorphisms of toll-like receptors 2 and 9 and severity and prognosis of bacterial meningitis in Chinese children.
Toll-like receptors (TLRs) play a crucial role in innate immunity, protecting the host from bacterial pathogens. We investigated whether bacterial meningitis (BM) in children was associated with gene polymorphisms in TLR2 (rs3804099), TLR3 (rs3775291 and rs3775290) and TLR9 (rs352139 and rs352140). Blood samples were taken from 218 child patients with confirmed BM and 330 healthy adult controls (HC) and polymorphisms of these genes were analyzed by PCR-based sequencing. For TLR2 rs3804099, frequencies of the minor allele C were markedly higher in patients with severe BM (defined as CSF glucose concentration ≤ 1.5 mmol/L and seizures) than those without (43.5% and 40.1% vs. 30.1% and 29.1%, p = 0.008 and p = 0.016, respectively). For TLR9 rs352139, patients who carried genotype AA and minor allele A developed seizures less often than those without (OR = 0.289, p = 0.003 and OR = 0.568, p = 0.004, respectively). However, for TLR9 rs352140, patients who carried genotype TT and minor allele T developed seizures more often than those without (OR = 3.385, p = 0.004 and OR = 1.767, p = 0.004, respectively). Our finding suggested that genetic variations in TLR2 and TLR9 are associated with severity and prognosis of bacterial meningitis in Chinese children. However, the results should be interpreted with caution since the number of subjects included was limited.


The Current State of Physics Plan Review Training in Medical Physics Residency Programs in North America.
This study aimed to identify the current state of residency training in physics plan reviews. A voluntary, anonymous survey was sent to all program directors of accredited therapeutic medical physics residency programs in North America. Survey questions were developed to determine whether and how residents are trained in physics plan reviews. Survey questions were developed using expert validation and cognitive pretesting. Using a prospectively approved study (COMIRB 18-1073), responses were collected from 70 program directors, representing a 70% response rate. All respondents (100%) designated patient safety to be the purpose of physics plan reviews. Of the respondents, 94% indicated that physicists should first receive training in physics plan reviews while in a residency program. The vast majority of respondents (99%) provide training to residents in physics plan reviews. Although 57 programs (81% of respondents) have residents perform physics plan reviews as part of clinical practice (with varying levels of independence), 13 programs (19% of respondents) do not. The majority of respondents use the following training methods: observe staff physicists (96%), perform supervised reviews on actual patients for training or clinical practice (93%), use a checklist (80%), and read reference materials (62%). Although simulation plans with embedded errors would be implemented by 71% of respondents, they are currently used in only 19% of programs. The present study is the first to characterize chart-check teaching practices in medical physics residency programs. The vast majority of programs currently train residents in physics plan reviews. The most common teaching methods are observing and performing physics plan reviews, but there is variability in the level of resident involvement in clinical practice for physics plan reviews. There is room for the field to consider advancing current training methods, which is especially important given the critical roles that physics plan reviews have with regard to patient safety.


Diet of patients after pouch surgery may affect pouch inflammation.
To investigate the diet of pouch patients compared to healthy controls, and to correlate pouch patients' diet with disease behavior. Pouch patients were recruited and prospectively followed-up at the Comprehensive Pouch Clinic at the Tel Aviv Sourasky Medical Center. Pouch behavior was determined based on clinical, endoscopic and histological criteria. Healthy age- and sex-matched volunteers were selected from the "MABAT" Israeli Nutrition and Public Health Governmental Study and served as the control group. All the participants completed a 106-item food frequency questionnaire categorized into food groups and nutritional values based on those used in the United States Department of Agriculture food pyramid and the Israeli food pyramid. Data on Dietary behavior, food avoidance, the use of nutritional supplements, physical activity, smoking habits, and body-mass index (BMI) were also obtained. Pouch patients who had familial adenomatous polyposis (n = 3), irritable pouch syndrome (n = 4), or patients whose pouch surgery took place less than one year previously (n = 5) were excluded from analysis. The pouch patients (n = 80) consumed significantly more from the bakery products food group (1.2 ± 1.4 servings/d vs 0.6 ± 1.1 servings/d, P < 0.05) and as twice as many servings from the oils and fats (4.8 ± 3.4 servings/d vs 2.4 ± 2 servings/d, P < 0.05), and the nuts and seeds food group (0.3 ± 0.6 servings/d vs 0.1 ± 0.4 servings/d, P < 0.05) compared to the controls (n = 80). The pouch patients consumed significantly more total fat (97.6 ± 40.5 g/d vs 84.4 ± 39 g/d, P < 0.05) and fat components [monounsaturated fatty acids (38.4 ± 16.4 g/d vs 30 ± 14 g/d, P < 0.001), and saturated fatty acids (30 ± 15.5 g/d vs 28 ± 14.1 g/d, P < 0.00)] than the controls. In contrast, the pouch patients consumed significantly fewer carbohydrates (305.5 ± 141.4 g/d vs 369 ± 215.2 g/d, P = 0.03), sugars (124 ± 76.2 g/d vs 157.5 ± 90.4 g/d, P = 0.01), theobromine (77.8 ± 100 mg/d vs 236.6 ± 244.5 mg/d, P < 0.00), retinol (474.4 ± 337.1 μg/d vs 832.4 ± 609.6 μg/d, P < 0.001) and dietary fibers (26.2 ± 15.4 g/d vs 30.7 ± 14 g/d, P = 0.05) than the controls. Comparisons of the food consumption of the patients without (n = 23) and with pouchitis (n = 45) showed that the former consumed twice as many fruit servings as the latter (3.6 ± 4.1 servings/d vs 1.8 ± 1.7 servings/d, respectively, P < 0.05). In addition, the pouchitis patients consumed significantly fewer liposoluble antioxidants, such as cryptoxanthin (399 ± 485 μg/d vs 890.1 ± 1296.8 μg/d, P < 0.05) and lycopene (6533.1 ± 6065.7 μg/d vs 10725.7 ± 10065.9 μg/d, P < 0.05), and less vitamin A (893.3 ± 516 μg/d vs 1237.5 ± 728 μg/d, P < 0.05) and vitamin C (153.3 ± 130 mg/d vs 285.3 ± 326.3 mg/d, P < 0.05) than the patients without pouchitis. The mean BMI of the pouchitis patients was significantly lower than the BMI of the patients with a normal pouch: 22.6 ± 3.2 vs 27 ± 4.9 (P < 0.001). Decreased consumption of antioxidants by patients with pouchitis may expose them to the effects of inflammatory and oxidative stress and contribute to the development of pouchitis.


Precision of using contralateral lesser trochanter as a landmark to prevent rotational malalignment in fracture shaft of femur: a human cadaveric study.
Rotational Malalignment is abnormal rotational alignment between proximal and distal parts of femoral bone. If there is more than 15 degrees of rotational malalignment in femoral bone, the patient will have abnormality of gait and they will have difficulties to perform their daily life activities. The chances to have rotational malalignment in femoral fracture are increased after intramedullary nailing which is more than plate and screws fixation. In this study, we used contralateral Lesser Trochanter to be the reference for rotational determiner. 17 pairs of never-broken cadeveric femur in the same person were randomly sampling and then measured the anteversion of both cadeveric femurs. Lessor trochanter of normal leg was measured to be as the landmark. The rotational malalignment was determined based on the differences between the starting angle and measured angle. Repeated measurements were done by the same investigators, other staffs, residents, and medical students to examine the precision. There was no statistically significance of both bone sides reported by intra-inter examiners (p-value = 0.904). However, we found high correlation for rotational malalignment in all 3 intra-examiners (p-value < 0.0001), and the intraclass-correlation coefficient was 0.919 (0.819-0.968). Moreover, there was also a good correlation in all 3 Inter-examiners; statistically significant (p-value = 0.009), and ICC was 0.726 (0.198-0.926). Our finding confirmed that the accuracy of contralateral lessor trochanter which was used to be a landmark for prevention of rotational malalignment in fracture of femoral shaft was highly reliable.


Primary ependymoma in the posterior mediastinum.
A 46-year-old woman was referred to our hospital because of back pain and an abnormality on chest imaging. Chest computed tomography showed a well-delineated tumor in the left paravertebral space. Histological analysis of the resected tumor revealed perivascular pseudorosettes, and immunoreactivity for glial fibrillary acidic protein established the diagnosis of ependymoma. A few cases have been reported in the ovary, broad ligament, sacrococcygeal region, lungs, and mediastinum, but the pathogenesis has not yet been clarified. Female predominance in these tumors and organogenesis of the sites may suggest a key to the pathogenesis.


The Impact of Air Pollution on Hospitalization for Cardiovascular and Cerebrovascular Disease in Shenyang, China.
The aim of this study was to investigate the overall impact of PM2.5, PM10, NO2, SO2, CO, and O3 on the admission of cardiovascular and cerebrovascular disease. We collected data on cardiovascular and cerebrovascular disease admissions from two hospitals in Shenyang Liaoning, China from Jan 2014 to Dec 2017, as well as daily measurements of six pollutants at 11 sites in Shenyang. The generalized additive model was used to assess the association between daily contaminants and admission to cardiovascular and cerebrovascular disease. The single-contamination model showed a significant correlation between NO2, O3, PM10 and cardiovascular and cerebrovascular diseases at lag0 day. Air pollutants had lag effects on different gender groups. Excess relative risks (ERs) associated with a 10 μg/m3 increase were 1.522(1.057, 1.988) on lag02 for NO2, 0.547% (0.367%, 0.728%), 0.133% (0.061%, 0.205%) on lag3 for O3 and PM10. The dual pollutant model showed that the effects of NO2, O3, and PM10 after adjusting the influence of other pollutants were still statistically significant. Short-term exposure to ambient air pollution (NO2, O3, and PM10) may be associated with an increased risk of daily cardiovascular and cerebrovascular admission, which may provide reliable evidence for further understanding of the potential adverse effects of air pollution on cardiovascular and cerebrovascular diseases.


Cytokeratin shedding in urine as a biological marker for bladder cancer: monoclonal antibody-based evaluation.
Cytokeratin shedding into urine was measured using a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) in 282 individuals. Samples included urine from normal controls, patients with urogenital conditions and bladder cancer patients. A monoclonal antibody prepared against cytokeratins extracted from a hyperkeratotic low grade squamous cell carcinoma (UNME/K1) was used in the assay. The results indicated reasonable levels of sensitivity (83%), specificity (67%) and overall accuracy (70%) in the detection of bladder cancer. The levels of sensitivity in detecting squamous and transitional cell carcinoma patients were 87 and 73% respectively. The low level of specificity was due to a high frequency of false positive results (55%) within the urogenital controls; this suggests that further immunochemical and immunohistopathological analyses of associated urothelial cytokeratins are required.


Hydroxytyrosol Alleviates Dextran Sulfate Sodium-Induced Colitis by Modulating Inflammatory Responses, Intestinal Barrier, and Microbiome.
Hydroxytyrosol (HT), a polyphenol derived from olive oil, was examined against dextran sulfate sodium (DSS)-induced colitis to study its potential in preventing colitis and the underlying mechanisms involved. The low dose and high dose of HT used in mice were 10 and 50 mg/kg, respectively. Research findings have shown that HT is effective in preventing colitis by alleviating the signs of colitis. HT intervention significantly reduces colitis markers such as myeloperoxidase (MPO) and proinflammatory cytokine (IL-6, IL-1β, and TNF-α). Also, mice treated with a high dose of HT showed increased secretion of antioxidant enzymes (heme oxygenase-1 (HO) and anti-inflammatory cytokine (IL-10) by 2.32- and 2.28-fold, respectively, in comparison to the DSS-treated group. Modulation effects of HT on the antioxidant signal pathway (NRF2) and the inflammatory pathway (NF-κB) were confirmed. Meanwhile, HT promoted the regeneration of the intestinal barrier and maintained intestinal functional homeostasis by boosting the regeneration of goblet cells and the expression of mucin protein (Muc2) and tight junction (TJ) proteins (claudin-1, occludin, and Zonula Occludens-1). Moreover, HT intervention obviously transformed the gut microbiota, leading to a lower abundance of inflammation-related microbes (e.g., Bacteroidaceae and Desulfovibrionaceae) and a higher level of short-chain fatty acids (SCFAs) producing bacteria (e.g., Lachnospiraceae, Muribaculaceae, ASF356, and Colidextribacter). Scientific evidence for the beneficial effect of the "Mediterranean diet" (MD) on intestinal health was achieved by elucidating the alleviation mechanism of hydroxytyrosol on colitis.


Social Intuition and Social Information in Physical Child Abuse Evaluation and Diagnosis.
Poor and minority children with injuries concerning for abuse are evaluated and diagnosed for abuse differentially. We hypothesized that 2 steps in the decision-making process would influence evaluation and diagnosis: social intuition from meeting the family and objective social information associated with child abuse risk. Between 2009 and 2013, 32 child abuse pediatricians (CAPs) submitted 730 child abuse consultations including original medical evaluations and diagnoses. CAPs evaluated and diagnosed each other's cases. Comparisons of evaluations and diagnoses were made by levels of social understanding available to the CAP: meeting the family (social intuition and information), reading the case (social information), and reading the case without social information. Evaluations were compared with a consensus gold standard by using logistic regression modeling adjusting for child and CAP characteristics. Diagnostic categories were compared by level of social understanding and diagnostic certainty by using contingency tables. CAPs without access to social intuition were approximately twice as likely to perform gold standard evaluations for neurotrauma and long bone fracture compared with CAPs who met families. Diagnostic agreement fell from 73.3% (95% confidence interval [CI]: 70.1%-76.5%) when social information was present to 66.5% (95% CI: 63.1%-70.0%) when social information was restricted. In cases with less certainty, agreement dropped to 51.3% (95% CI: 46.0%-56.7%). Social intuition and information play a role in the physical child abuse decision-making process, which may contribute to differential diagnosis. Simple interventions including decision tools, check lists, and peer review may structure evaluations to ensure children's equal treatment.


Data-driven quantification of the robustness and sensitivity of cell signaling networks.
Robustness and sensitivity of responses generated by cell signaling networks has been associated with survival and evolvability of organisms. However, existing methods analyzing robustness and sensitivity of signaling networks ignore the experimentally observed cell-to-cell variations of protein abundances and cell functions or contain ad hoc assumptions. We propose and apply a data-driven maximum entropy based method to quantify robustness and sensitivity of Escherichia coli (E. coli) chemotaxis signaling network. Our analysis correctly rank orders different models of E. coli chemotaxis based on their robustness and suggests that parameters regulating cell signaling are evolutionary selected to vary in individual cells according to their abilities to perturb cell functions. Furthermore, predictions from our approach regarding distribution of protein abundances and properties of chemotactic responses in individual cells based on cell population averaged data are in excellent agreement with their experimental counterparts. Our approach is general and can be used to evaluate robustness as well as generate predictions of single cell properties based on population averaged experimental data in a wide range of cell signaling systems.


Clinical, pathological and genetic features of primary mediastinal large B-cell lymphomas and mediastinal gray zone lymphomas in children.
Background Primary mediastinal large B-cell lymphoma is a rare lymphoma accounting for no more than 3% of all B-cell lymphomas in children and adolescents. However, patients in this young age group with this lymphoma have the shortest event-free survival of patients with any B-cell lymphoma under current standard chemotherapy protocols. Lymphomas with features intermediate between primary mediastinal large B-cell lymphoma and classical Hodgkin's lymphoma (mediastinal gray zone lymphomas) have been acknowledged in the latest World Health Organization classification. Recent studies suggest that mediastinal gray zone lymphomas have an aggressive clinical course whereas patients, at least adult ones, with primary mediastinal large B-cell lymphoma might respond very well to chemotherapy in combination with anti-CD20 antibody. We aimed to evaluate whether biological differences or so far unrecognized admixed mediastinal gray zone lymphomas might explain the relatively poor outcome of pediatric patients with apparent primary mediastinal large B-cell lymphoma. We, therefore, performed a retrospective histopathological, immunohistochemical and interphase cytogenetic analysis of 52 pediatric lymphomas. The childhood primary mediastinal large B-cell lymphomas (n=44) showed a similar pattern of histology, immunophenotype and gains at 9p (59%) and 2p (41%) as adult cases, as determined from published data. We identified only four so far unrecognized cases of mediastinal gray zone lymphoma among 52 lymphomas registered in previous trials. Conclusions Mediastinal gray zone lymphoma is very rare in children and adolescents. It does, therefore, seem unlikely that these lymphomas account for the unsatisfactory clinical results with current therapy protocols in pediatric patients. These data have major implications for the design of future treatment protocols for mediastinal lymphomas in children and adolescents.


Biosynthesis and desaturation of prokaryotic galactolipids in leaves and isolated chloroplasts from spinach.
Mono- and digalactosyldiacylglycerol (MGDG and DGDG) were isolated from the leaves of sixteen 16:3 plants. In all of these plant species, the sn-2 position of MGDG was more enriched in C(16) fatty acids than sn-2 of DGDG. The molar ratios of prokaryotic MGDG to prokaryotic DGDG ranged from 4 to 10. This suggests that 16:3 plants synthesize more prokaryotic MGDG than prokaryotic DGDG. In the 16:3 plant Spinacia oleracea L. (spinach), the formation of prokaryotic galactolipids was studied both in vivo and in vitro. In intact spinach leaves as well as in chloroplasts isolated from these leaves, radioactivity from [1-(14)C]acetate accumulated 10 times faster in MGDG than in DGDG. After 2 hours of incorporation, most labeled galactolipids from leaves and all labeled galactolipids from isolated chloroplasts were in the prokaryotic configuration. Both in vivo and in vitro, the desaturation of labeled palmitate and oleate to trienoic fatty acids was higher in MGDG than in DGDG. In leaves, palmitate at the sn-2 position was desaturated in MGDG but not in DGDG. In isolated chloroplasts, palmitate at sn-2 similarly was desaturated only in MGDG, but palmitate and oleate at the sn-1 position were desaturated in MGDG as well as in DGDG. Apparently, palmitate desaturase reacts with sn-1 palmitate in either galactolipid, but does not react with the sn-2 fatty acid of DGDG. These results demonstrate that isolated spinach chloroplasts can synthesize and desaturate prokaryotic MGDG and DGDG. The finally accumulating molecular species, MGDG(18:3/16:3) and DGDG(18:3/16:0), are made by the chloroplasts in proportions similar to those found in leaves.


Differential regulation of IGF-I, its receptor and GH receptor mRNAs in the right ventricle and caval vein in volume-loaded genetically hypertensive and normotensive rats.
It has been suggested, mainly by in vitro findings, that cardiovascular tissue in the spontaneously hypertensive rat (SHR) should be more prone to proliferate/hypertrophy than that of the Wistar-Kyoto rat (WKY). The present study tests the hypothesis that the tissue of the low-pressure compartment in SHR, being structurally similar to that of the WKY, shows an increased growth response due to activation of the GH-IGF-I system. An aortocaval fistula (ACF) was induced in 64 SHR and WKY male rats and 44 rats served as controls. They were all followed for 1, 2, 4 and 7 days after surgery. In separate groups of SHR (n=4) and WKY (n=3), central venous pressure was measured by telemetry recordings prior to opening of the fistula and for up to 16 h post-surgery. Systolic blood pressure was measured during the week post-surgery. The right ventricular (RV) and the caval vein IGF-I mRNA and RV IGF-I receptor and GH receptor mRNAs were quantitated by means of solution hybridisation assay. In rats with ACF the systolic blood pressure decreased, approximately 29% in SHR and 16% in WKY between 1 and 7 days post-surgery (P<0.05, n=5-6 in each group). SHR with ACF showed a transient elevation in central venous pressure vs WKY. Within the week following fistula induction both strains showed a similar, pronounced increase in RV hypertrophy. SHR with ACF showed a smaller, or even blunted, overall response with respect to activation of the GH-IGF-I system compared with WKY, the latter showing clear-cut elevation of gene expressions. Two days after shunt opening in SHR, RV and caval vein IGF-I mRNA increased by 57% and 108% (P<0.05 for both, n=5-6 in each group) respectively, and these expressions were then turned off, whereas RV GH receptor and IGF-I receptor mRNA expression remained unaffected compared with WKY rats. WKY rats showed on average a later and a greater response of GH-IGF-I system mRNA expression vs SHR. The present in vivo study suggests that the SHR requires less activation of the GH-IGF-I system for creating a given adaptive structural growth response.


Selective Pressures Explain Differences in Flower Color among Gentiana lutea Populations.
Flower color variation among plant populations might reflect adaptation to local conditions such as the interacting animal community. In the northwest Iberian Peninsula, flower color of Gentiana lutea varies longitudinally among populations, ranging from orange to yellow. We explored whether flower color is locally adapted and the role of pollinators and seed predators as agents of selection by analyzing the influence of flower color on (i) pollinator visitation rate and (ii) escape from seed predation and (iii) by testing whether differences in pollinator communities correlate with flower color variation across populations. Finally, (iv) we investigated whether variation in selective pressures explains flower color variation among 12 G. lutea populations. Flower color influenced pollinator visits and differences in flower color among populations were related to variation in pollinator communities. Selective pressures on flower color vary among populations and explain part of flower color differences among populations of G. lutea. We conclude that flower color in G. lutea is locally adapted and that pollinators play a role in this adaptation.


Moving upward in a downturn.
As the recent bursting of the new economy bubble has shown, business cycles are still wih us. The question, then, is, what executives should do to help their companies weather these downturns. As in so many instances, there are conventional approaches that appear to make sense in the short term. But while these approaches seem reasonable in the heat of the moment, they can eventually damage competitive positions and financial performance. Drawing on extensive research of Fortune 500 companies that have lived through industry downturns and economic recessions over the past two decades, Darrell Rigby, a director of Bain & Company, reveals how companies need to go against the grain of convention and exploit industry downturns to harness their unique opportunities for upward mobility. The author explains that every downturn goes through three phases. He examines each phase and shows how successful players navigate the huge waves of a downturn. Smart executives, he says, don't panic: they look bad news in the eye and institutionalize an approach to detecting storms. Rather than hedge their bets through diversification, they focus on their core businesses and spend to gain market share. They manage costs relentlessly during good times and bad. They keep a long-term view and strive to maintain the loyalty of employees, suppliers, and customers. And coming out of the downturn, they maintain momentum in their businesses to stay ahead of the competition they've already surpassed. Every industry will face periodic downturns of varying severity, says Rigby. But executives with the vision and ingenuity to take unconventional approaches can buoy their companies to new heights.


Exercise and antiretroviral adherence in adults living with HIV: A systematic review.
This systematic review assessed the relationship between exercise and ART adherence in adults living with HIV. A comprehensive search through June 2020 for relevant studies was conducted, and PRISMA guidelines were followed. To be included, studies had to meet the following criteria: (a) published in a peer-reviewed journal; and (b) examined the relationship between exercise and ART adherence. A total of 4310 studies were identified, and nine were included. The majority (five out of nine) of studies found a significant and positive relationship between exercise and ART adherence. Strengths, limitations, and future directions are discussed.


[The role of vitamin D deficiency in the pathogenesis of falls and fractures].
The diverse effects of vitamin D in human body became known during the last years. Vitamin D deficiency causes many problems in medical care. Important roles of vitamin D are the regulation of calcium metabolism and the effect on bone metabolism. The authors review literature data on vitamin D deficiency recognized as an important risk factor in the pathogenesis of falls and fractures and they call attention of Hungarian physicians to the importance of vitamin D substitution. Supplementation of vitamin D deficiency is particularly important in the elderly age-group.


Mutant and wild-type alpha-synuclein interact with mitochondrial cytochrome C oxidase.
Alpha-synuclein, a presynaptic protein, was found to be the major component in the Lewy bodies (LB) in both inherited and sporadic Parkinson's disease (PD). Furthermore, rare mutations of alpha-synuclein cause autosomal-dominant PD. However, it is unknown how alpha-synuclein is involved in the pathogenesis of nigral degeneration in PD. In this study, we examine the protein-protein interactions of wild-type and mutant (A53T) a-synuclein with adult human brain cDNA expression library using the yeast two-hybrid technique. We found that both normal and mutant alpha-synuclein specifically interact with the mitochondrial complex IV enzyme, cytochrome C oxidase (COX). Wild-type and mutant alpha-synuclein genes were further fused with c-Myc tag and translated in rabbit reticulocyte lysate. Using anti-c-Myc antibody, we demonstrated that both wild-type and mutant alpha-synuclein, coimmunoprecipitated with COX. We also showed that potassium cyanide, a selective COX inhibitor, synergistically enhanced the sensitivity of SH-SY5Y neuroblastoma cells to dopamine-induced cell death. In conclusion, we found specific protein-protein interactions of alpha-synuclein, a major LB protein, to COX, a key enzyme of the mithochondrial respiratory system. This interaction suggests that alpha-synuclein aggregation may contribute to enhance the mitochondrial dysfunction, which might be a key factor in the pathogenesis of PD.


Water-borne transmission drives avian influenza dynamics in wild birds: the case of the 2005-2006 epidemics in the Camargue area.
Transmission and persistence of avian influenza viruses (AIV) among wildlife remains an unresolved issue because it depends both on the ecology of the host (e.g. population density, migration) and on the environment (e.g. AIV persistence in water). We have developed a mathematical model that accounts for both AIV epidemics and bird community dynamics. The model is parameterized using bird counts and AIV prevalence data. Results suggest that the transmission patterns driving the dynamics of infection at our study site (Camargue, South of France) involved both a density-dependent and a water-borne transmission processes. Water-borne transmission is, however, the main determinant of the disease dynamics and observed prevalence level. This pattern of transmission highlights the importance of the persistence of viral particles in water in AIV dynamics in wild birds.


Impulsivity on a Go/No-go task for intravenous cocaine or food in male and female rats selectively bred for high and low saccharin intake.
The purpose of this study was to examine a form of impulsive behavior (impaired inhibition) using cocaine or food reward in addiction-prone and addiction-resistant rats that were bred for high saccharin (HiS) or low saccharin (LoS) intake, respectively. A Go/No-go procedure was used to examine cocaine and food reinforcement (Go component) and the inhibition of responding during a subsequent period of nonreward (No-go component). Rats were initially trained to self-administer intravenous cocaine (0.4 mg/kg) under an FR 1 schedule during daily Go/No-go sessions consisting of three components of cocaine reinforcement (Go) alternating with two nonreward components (No-go), each signaled by different stimuli. Responding and drug intake were compared under three FR values (FR 1, FR 3, and FR 5) and three cocaine doses (0.2, 0.4, and 0.8 mg/kg). A similar Go/No-go procedure was used with food reinforcement and the same three FR conditions. During the Go components for intravenous cocaine, female rats self-administered more infusions at the 0.2 and 0.4 mg/kg doses than males, indicating a sex difference in cocaine intake. During the No-go periods under the cocaine condition, HiS rats and females responded significantly more than LoS rats and males, indicating phenotype and sex differences in impaired inhibition. During the Go components with food reward, males responded more and earned more pellets than females, but there were no phenotype or sex differences in No-go responding (impulsivity). The results indicate that HiS rats and females are more prone than LoS rats and males to impulsive drug-seeking behavior.


Neural stem cells and neurogenesis in the adult zebrafish brain: origin, proliferation dynamics, migration and cell fate.
Lifelong neurogenesis in vertebrates relies on stem cells producing proliferation zones that contain neuronal precursors with distinct fates. Proliferation zones in the adult zebrafish brain are located in distinct regions along its entire anterior-posterior axis. We show a previously unappreciated degree of conservation of brain proliferation patterns among teleosts, suggestive of a teleost ground plan. Pulse chase labeling of proliferating populations reveals a centrifugal movement of cells away from their places of birth into the surrounding mantle zone. We observe tangential migration of cells born in the ventral telencephalon, but only a minor rostral migratory stream to the olfactory bulb. In contrast, the lateral telencephalic area, a domain considered homologous to the mammalian dentate gyrus, shows production of interneurons and migration as in mammals. After a 46-day chase, newborn highly mobile cells have moved into nuclear areas surrounding the proliferation zones. They often show HuC/D immunoreactivity but importantly also more specific neuronal identities as indicated by immunoreactivity for tyrosine hydroxylase, serotonin and parvalbumin. Application of a second proliferation marker allows us to recognize label-retaining, actively cycling cells that remain in the proliferation zones. The latter population meets two key criteria of neural stem cells: label retention and self renewal.


Neuropsychological and Behavioural Short-Term Effects of Cognitive Remediation Therapy in Adolescent Anorexia Nervosa: A Pilot Study.
Cognitive remediation therapy (CRT) aims to strengthen weak cognitive flexibility and central coherence in adult and adolescent anorexia nervosa (AN). Currently, there are no studies in adolescents with AN that control for learning effects because of re-testing while evaluating CRT. Twenty in- and outpatients with AN aged 12 to 18 years received CRT. Assessment took place directly before and after the intervention. Performance was compared to 20 age-, gender-, IQ-, and test-retest interval matched healthy controls, which did not receive CRT. AN patients showed an improvement in flexibility on neuropsychological assessment directly after CRT, whereas HC did not improve over time. Self-report assessment of flexibility, as well as central coherence, did not show significant improvement after CRT. Results suggest that CRT may be beneficial for enhancing flexibility in adolescents with AN. However, randomized controlled studies are essential to determine the actual efficacy of this intervention.


Bibliometric Analysis of Manuscript Characteristics That Influence Citations: A Comparison of Six Major Radiology Journals.
The objective of our study was to investigate radiology manuscript characteristics that influence citation rate, capturing features of manuscript construction that are discrete from study design. Consecutive articles published from January 2004 to June 2004 were collected from the six major radiology journals with the highest impact factors: Radiology (impact factor, 5.076), Investigative Radiology (2.320), American Journal of Neuroradiology (AJNR) (2.384), RadioGraphics (2.494), European Radiology (2.364), and American Journal of Roentgenology (2.406). The citation count for these articles was retrieved from the Web of Science, and 29 article characteristics were tabulated manually. A point-biserial correlation, Spearman rank-order correlation, and multiple regression model were performed to predict citation number from the collected variables. A total of 703 articles-211 published in Radiology, 48 in Investigative Radiology, 106 in AJNR, 52 in RadioGraphics, 129 in European Radiology, and 157 in AJR-were evaluated. Punctuation was included in the title in 55% of the articles and had the highest statistically significant positive correlation to citation rate (point-biserial correlation coefficient [rpb] = 0.85, p < 0.05). Open access status provided a low-magnitude, but significant, correlation to citation rate (rpb = 0.140, p < 0.001). The following variables created a significant multiple regression model to predict citation count (p < 0.005, R2 = 0.186): study findings in the title, abstract word count, abstract character count, total number of words, country of origin, and all authors in the field of radiology. Using bibliometric knowledge, authors can craft a title, abstract, and text that may enhance visibility and citation count over what they would otherwise experience.


Polymorphic mutation frequencies of clinical and environmental Stenotrophomonas maltophilia populations.
Mutation frequencies were studied in 174 Stenotrophomonas maltophilia isolates from clinical and nonclinical environments by detecting spontaneous rifampin-resistant mutants in otherwise-susceptible populations. The distribution of mutation frequencies followed a pattern similar to that found for other bacterial species, with a modal value of 1 x 10(-8). Nevertheless, the proportion of isolates showing mutation frequencies below the modal value (hypomutators) was significantly higher for S. maltophilia than those so far reported in other organisms. Low mutation frequencies were particularly frequent among environmental S. maltophilia strains (58.3%), whereas strong mutators were found only among isolates with a clinical origin. These results indicate that clinical environments might select bacterial populations with high mutation frequencies, likely by second-order selection processes. In several of the strong-mutator isolates, functional-complementation assays with a wild-type allele of the mutS gene demonstrated that the mutator phenotype was due to the impairment of MutS activity. In silico analysis of the amino acid changes present in the MutS proteins of these hypermutator strains in comparison with the normomutator isolates suggests that the cause of the defect in MutS might be a H683P amino acid change.


Coronavirus: An insight into global research until outbreak of COVID-19 and its implications for the future.
The currently prevailing global threat of COVID-19 caused the publication numbers on coronaviruses to explode. The awareness of the scientific and public community is enormous. But what about the sense of all these undertakings and what can be learned about the future for a better understanding? These questions were answered with established bibliometric analyses of the time until the avalanche of publications unfolded. Chronological, geographical aspects of publication output on coronavirus were also evaluated under the influence of epidemiological and socio-economic parameters. The trend in publication and citation numbers shows the strong influence of the past pandemics SARS and MERS with an untypical decline afterward. Research is becoming increasingly multidisciplinary over time. The USA and China, as the countries with the highest number of publications, are being displaced by other countries in the consideration of socio-economic and epidemiological aspects, which shows the effect of regional interest in corona research. A significant correlation was found between the number of SARS cases per country and related publications, while no correlation was found for MERS cases and articles. The results underline the need for sustainable and forward-looking approaches that should not end with the containment of COVID-19.


Spondylolysis.
Spondylolysis is a bony defect of the pars interarticularis and most often results from repetitive stress. Although spondylolysis is usually asymptomatic, symptomatic spondylolysis is the most common cause of identifiable back pain in children and adolescent athletes. A thorough history and physical exam, as well as appropriate imaging studies are helpful in diagnosis. General first-ine therapy for spondylolysis is conservative and consists of rest from sports, core strengthening, as well as spinal bracing. Patients who have failed conservative therapy may consider surgical repair. This article aims to review the epidemiology, pathophysiology, presentation, and treatment options of spondylolysis.


Hypoxia-Inducible Lysine Methyltransferases: G9a and GLP Hypoxic Regulation, Non-histone Substrate Modification, and Pathological Relevance.
Oxygen sensing is inherent among most animal lifeforms and is critical for organism survival. Oxygen sensing mechanisms collectively trigger cellular and physiological responses that enable adaption to a reduction in ideal oxygen levels. The major mechanism by which oxygen-responsive changes in the transcriptome occur are mediated through the hypoxia-inducible factor (HIF) pathway. Upon reduced oxygen conditions, HIF activates hypoxia-responsive gene expression programs. However, under normal oxygen conditions, the activity of HIF is regularly suppressed by cellular oxygen sensors; prolyl-4 and asparaginyl hydroxylases. Recently, these oxygen sensors have also been found to suppress the function of two lysine methyltransferases, G9a and G9a-like protein (GLP). In this manner, the methyltransferase activity of G9a and GLP are hypoxia-inducible and thus present a new avenue of low-oxygen signaling. Furthermore, G9a and GLP elicit lysine methylation on a wide variety of non-histone proteins, many of which are known to be regulated by hypoxia. In this article we aim to review the effects of oxygen on G9a and GLP function, non-histone methylation events inflicted by these methyltransferases, and the clinical relevance of these enzymes in cancer.


The Role of Retrospective Data Review in the Personal Use of Real-Time Continuous Glucose Monitoring: Perceived Impact on Quality of Life and Health Outcomes.
Background: To explore whether regularly reviewing one's own retrospective continuous glucose monitoring (CGM) data might be linked with perceived quality of life (QoL) and glycemic benefits. Methods: Adults with type 1 diabetes (N = 300) or insulin-using type 2 diabetes (N = 198) using the Dexcom G5 Mobile or G6 Real-Time CGM (RT-CGM) system and receiving the weekly CLARITY summary report of their glucose data completed a survey exploring their use of the report and its perceived value and impact on QoL and glycemic outcomes. Regression analyses examined whether personal use of the report was associated with QoL, perceived glycemic outcomes, and RT-CGM metrics. Results: The majority reported that receiving and viewing the report contributed to improved hypoglycemic confidence (75.9%) and overall well-being (50.0%), reduced diabetes distress (59.3%-74.1%), and helped to improve A1C (73.1%) and reduce problems with hypoglycemia (61.8%) and chronic hyperglycemia (73.1%). Regularly reviewing the report with family or friends (positive predictor) and doing nothing with the report's information (negative predictor) were independently associated with QoL and perceived glycemic outcomes. Surprisingly, both predictors were also associated with poorer glycemic control (e.g., greater % time above range >180). Conclusions: These findings suggest that receiving a weekly RT-CGM summary report may contribute to QoL and health benefits, especially if the individual chooses to actively review and make use of the report's findings and openly reviews the findings with family or friends. Prospective studies are needed to more precisely determine how retrospective RT-CGM data summaries can best be presented and utilized effectively by adults with diabetes to enhance health outcomes.


The addition of mycophenolate mofetil to antiretroviral therapy including abacavir is associated with depletion of intracellular deoxyguanosine triphosphate and a decrease in plasma HIV-1 RNA.
Mycophenolic acid (MPA) enhances the in vitro activity of abacavir (ABC) and other nucleoside analog reverse transcriptase inhibitors (NRTIs) against sensitive and NRTI-resistant HIV-1. This may occur via depletion of intracellular deoxyguanosine triphosphate (dGTP). Mycophenolate mofetil (MMF) 500 mg twice daily was added as a single agent to the antiretroviral regimens of five patients failing maximal available therapy. Therapy included ABC, and in most cases didanosine (DDI) and tenofovir (TDF). At entry, mean plasma HIV-1 RNA (VL) was 5.02 log copies/mL (median 4.78, range 4.71-5.63) and mean CD4 count was 106/microL (median 117, range 11-174). MMF was well tolerated. CD4 cell counts did not change significantly from baseline for up to 60 weeks of follow-up. Three of five subjects had VL declines of >0.5 log copies/mL immediately after adding MMF; a fourth subject had a sustained decline of >0.5 log copies/mL after week 8. Declines of >0.5 log copies/mL were lost in two patients at 6 and 8 weeks, and persisted in two patients at 36 and 60 weeks of follow-up, respectively. An increase in the ratio of carbovir triphosphate (CBV-TP), the active antiviral metabolite of ABC, to dGTP was documented in 3 of 4 subjects in temporal association with decreased VL. Trough plasma MPA levels ranged from 0.26-1.67 microg/mL; peak levels 90 minutes after dosing from 1.20-7.77 microg/mL. AUC of MPA appeared little changed when measured over 28 weeks of therapy. Declines in VL were observed in association with measurable changes in the CBV-TP/dGTP ratio in some patients, whereas MPA AUC was below the 30-60 microg*hr/mL range targeted in organ transplantation. The possibility that MMF may enhance the effect of selected NRTIs and be tolerated in late stage HIV disease deserves careful randomized study.


Predominance of defective proviral sequences in an HIV + long-term non-progressor.
We examined the accessory genes and envelope V3 region of provirus obtained over a 5 year period from an HIV+ long-term non-progressor with very low viral load and no in vitro recoverable virus during that same time span. LTR sequences supported normal Tat-mediated promoter activity. Multiple clones of nef sequences were highly conserved with < 10% containing frame shift or stop codon mutations. Functional analysis of the predominant nef sequence indicated wild type downregulation of surface CD4 and good function in a complementation infectivity assay. By contrast, inactivating mutations were found in 64% of amplicons containing vif, vpr, vpu, tat1, and rev1, and in 41% of amplicons containing env V3. Identical inactive sequences were obtained at an interval of 2 years, suggesting persistence of quiescent defective provirus in a long-lived clonal cell population. Furthermore, genetic distance versus time analysis revealed an absence of progressive evolution or arborization of quasispecies over time. This contrasts with data generated from other asymptomatic HIV+ individuals. The non-progressive pattern of env sequence diversity and low R2 for genetic divergence over time suggests that the defective provirus circulating in the periphery of this patient represents a randomly sampled 'fossil record' of earlier replication competent HIV-1 genomes.


iTRAQ-Based Quantitative Proteomic Analysis of Antibacterial Mechanism of Milk-Derived Peptide BCp12 against Escherichia coli.
BCp12 is a novel casein-derived antibacterial peptide with a broad-spectrum antibacterial effect. However, its action mechanism against E. coli is unknown. In this study, the growth curve showed that BCp12 had excellent antibacterial activity against E. coli. Red (propidium iodide staining) and green (fluorescein isothiocyanate staining) fluorescence signals were detected at the edges of the E. coli cells treated with BCp12. scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images showed that E. coli cells became rough and shrunken, and part of the cell contents leaked to form a cavity. Furthermore, the iTRAQ proteome analysis showed that 193 and 174 proteins were significantly up-regulated and down-regulated, respectively, after BCp12 treatment. Four enzymes involved in fatty acid degradation of E. coli were down-regulated, disrupting the synthesis of cell membranes. Molecular docking and gel retardation assays showed that BCp12 could bind to genes encoding four key enzymes involved in the fatty acid degradation pathway through hydrogen bonding and hydrophobic interactions, thus significantly inhibiting their activities. Overall, the results indicate that BCp12 inhibits the growth of E. coli, causing metabolic disorders, thus destroying the structure of cell membranes.


Effects of Training Status and Exercise Mode on Global Gene Expression in Skeletal Muscle.
The aim of this study was to investigate differences in skeletal muscle gene expression of highly trained endurance and strength athletes in comparison to untrained individuals at rest and in response to either an acute bout of endurance or strength exercise. Endurance (ET, n = 8, VO2max 67 ± 9 mL/kg/min) and strength athletes (ST, n = 8, 5.8 ± 3.0 training years) as well as untrained controls (E-UT and S-UT, each n = 8) performed an acute endurance or strength exercise test. One day before testing (Pre), 30 min (30'Post) and 3 h (180'Post) afterwards, a skeletal muscle biopsy was obtained from the m. vastus lateralis. Skeletal muscle mRNA was isolated and analyzed by Affymetrix-microarray technology. Pathway analyses were performed to evaluate the effects of training status (trained vs. untrained) and exercise mode-specific (ET vs. ST) transcriptional responses. Differences in global skeletal muscle gene expression between trained and untrained were smaller compared to differences in exercise mode. Maximum differences between ET and ST were found between Pre and 180'Post. Pathway analyses showed increased expression of exercise-related genes, such as nuclear transcription factors (NR4A family), metabolism and vascularization (PGC1-α and VEGF-A), and muscle growth/structure (myostatin, IRS1/2 and HIF1-α. The most upregulated genes in response to acute endurance or strength exercise were the NR4A genes (NR4A1, NR4A2, NR4A3). The mode of acute exercise had a significant effect on transcriptional regulation Pre vs. 180'Post. In contrast, the effect of training status on human skeletal muscle gene expression profiles was negligible compared to strength or endurance specialization. The highest variability in gene expression, especially for the NR4A-family, was observed in trained individuals at 180'Post. Assessment of these receptors might be suitable to obtain a deeper understanding of skeletal muscle adaptive processes to develop optimized training strategies.


Chemical characterization and immunomodulatory properties of polysaccharides isolated from probiotic Lactobacillus casei LOCK 0919.
The Lactobacillus casei strain, LOCK 0919, is intended for the dietary management of food allergies and atopic dermatitis (LATOPIC® BIOMED). The use of a probiotic to modulate immune responses is an interesting strategy for solving imbalance problems of gut microflora that may lead to various disorders. However, the exact bacterial signaling mechanisms underlying such modulations are still far from being understood. Here, we investigated variations in the chemical compositions and immunomodulatory properties of the polysaccharides (PS), L919/A and L919/B, which are produced by L. casei LOCK 0919. By virtue of their chemical features, such PS can modulate the immune responses to third-party antigens. Our results revealed that L919/A and L919/B could both modulate the immune response to Lactobacillus planatarum WCFS1, but only L919/B could alter the response of THP-1 cells (in terms of tumor necrosis factor alpha production) to L. planatarum WCFS1 and Escherichia coli Nissle 1917. The comprehensive immunochemical characterization is crucial for the understanding of the biological function as well as of the bacteria-host and bacteria-bacteria cross-talk.


Airway Mucins Inhibit Oxidative and Non-Oxidative Bacterial Killing by Human Neutrophils.
Neutrophil killing of bacteria is mediated by oxidative and non-oxidative mechanisms. Oxidants are generated through the NADPH oxidase complex, whereas antimicrobial proteins and peptides rank amongst non-oxidative host defenses. Mucus hypersecretion, deficient hydration and poor clearance from the airways are prominent features of cystic fibrosis (CF) lung disease. CF airways are commonly infected by Pseudomonas aeruginosa and Burkholderia cepacia complex bacteria. Whereas the former bacterium is highly sensitive to non-oxidative killing, the latter is only killed if the oxidative burst is intact. Despite an abundance of neutrophils, both pathogens thrive in CF airway secretions. In this study, we report that secreted mucins protect these CF pathogens against host defenses. Mucins were purified from CF sputum and from the saliva of healthy volunteers. Whereas mucins did not alter the phagocytosis of Pseudomonas aeruginosa and Burkholderia cenocepacia by neutrophils, they completely suppressed bacterial killing. Accordingly, mucins markedly inhibited non-oxidative bacterial killing by neutrophil granule extracts, or by lysozyme and the cationic peptide, human β defensin-2 (HBD2). Mucins also suppressed the neutrophil oxidative burst through a charge-dependent mechanism that could be reversed by the cationic aminoglycoside, tobramycin. Our data indicate that airway mucins protect Gram-negative bacteria against neutrophil killing by suppressing the oxidative burst and inhibiting the bactericidal capacity of cationic proteins and peptides. Mucin hypersecretion, dehydration, stasis and anionic charge represent key therapeutic targets for improving host defenses and airway inflammation in CF and other muco-secretory airway diseases.


Dispersion capacity of Triatoma sherlocki, Triatoma juazeirensis and laboratory-bred hybrids.
Flight dispersion is recognized as one of the most important mechanisms for triatomine house infestation. Triatoma sherlocki and T. juazeirensis are closely related species that occur within the same ecotope and their possible reproductive boundaries are unknown. T. sherlocki has shorter wings than T. juazeirensis; a characteristic that possibly implies in reduced flight dispersion, however, this species has been found to invade and colonize homes in Bahia, Brazil. Here, we tested the flight potential of T. sherlocki, compared to that of T. juazeirensis and laboratory-bred hybrids. Insects were kept in an apparatus designed to distinguish flyers from nonflyers. Fifty-one and 53% of T. juazeirensis and hybrids were flyers respectively, whereas no T. sherlocki were recorded to fly. Morphometric analysis of the main structures associated with the locomotor abilities showed that hybrids exhibited intermediate size for most of characters. The width of pronotum of both hybrids and T. juazeirensis was significantly larger than T. sherlocki. We suggested that lack of flight ability of T. sherlocki is possibly a result of reduced wing size and distinct shape, combined with undeveloped flight muscles in a shorter thoracic box. The mobility of T. sherlocki might be compensated by its significantly longer legs, and may possibly increase its ability to invade human dwellings by active dispersion. What is more, this study showed that hybrids between T. sherloki and T. juazeirensis have intermediate morphological characters that may give them higher fitness than their parents, and thus may advance the process of house infestation by either fight or walking in case of an eventual natural hybridization.


Cylindrical PVDF film transmitters and receivers for air ultrasound.
Cylindrical polyvinylidene fluoride (PVDF) film transducers for transmission and reception of 40-kHz ultrasonic waves in air have been investigated. A key feature of such transducers is their omni-directional polar response. An optimized structure comprises a cylindrical PVDF film element resting on a spool without a mechanical bond to it. Various key design equations to obtain the required ultrasonic performance both as transmitter and receiver are shown, which include resonance frequency, acoustic pressure, angle performance, back air cavity effect, and receiver sensitivity. Measurements of actual frequency response of transmitter output and receiver sensitivity, angular performance, back air space effect, and temperature effect are presented. The results agree well with the theoretical predictions. It has been shown that this device is well-suited for practical application as an ultrasonic ranging device.


Evolution and modulation of intracellular calcium release during long-lasting, depleting depolarization in mouse muscle.
Intracellular calcium signals regulate multiple cellular functions. They depend on release of Ca(2+) from cellular stores into the cytosol, a process that in many types of cells appears to be tightly controlled by changes in [Ca(2+)] within the store. In contrast with cardiac muscle, where depletion of Ca(2+) in the sarcoplasmic reticulum is a crucial determinant of termination of Ca(2+) release, in skeletal muscle there is no agreement regarding the sign, or even the existence of an effect of SR Ca(2+) level on Ca(2+) release. To address this issue we measured Ca(2+) transients in mouse flexor digitorum brevis (FDB) skeletal muscle fibres under voltage clamp, using confocal microscopy and the Ca(2+) monitor rhod-2. The evolution of Ca(2+) release flux was quantified during long-lasting depolarizations that reduced severely the Ca(2+) content of the SR. As in all previous determinations in mammals and non-mammals, release flux consisted of an early peak, relaxing to a lower level from which it continued to decay more slowly. Decay of flux in this second stage, which has been attributed largely to depletion of SR Ca(2+), was studied in detail. A simple depletion mechanism without change in release permeability predicts an exponential decay with time. In contrast, flux decreased non-exponentially, to a finite, measurable level that could be maintained for the longest pulses applied (1.8 s). An algorithm on the flux record allowed us to define a quantitative index, the normalized flux rate of change (NFRC), which was shown to be proportional to the ratio of release permeability P and inversely proportional to Ca(2+) buffering power B of the SR, thus quantifying the 'evacuability' or ability of the SR to empty its content. When P and B were constant, flux then decayed exponentially, and NFRC was equal to the exponential rate constant. Instead, in most cases NFRC increased during the pulse, from a minimum reached immediately after the early peak in flux, to a time between 200 and 250 ms, when the index was no longer defined. NFRC increased by 111% on average (in 27 images from 18 cells), reaching 300% in some cases. The increase may reflect an increase in P, a decrease in B, or both. On experimental and theoretical grounds, both changes are to be expected upon SR depletion. A variable evacuability helps maintain a constant Ca(2+) output under conditions of diminishing store Ca(2+) load.


Bioinformatics approaches in clinical proteomics.
Protein expression profiling is increasingly being used to discover, validate and characterize biomarkers that can potentially be used for diagnostic purposes and to aid in pharmaceutical development. Correct analysis of data obtained from these experiments requires an understanding of the underlying analytic procedures used to obtain the data, statistical principles underlying high-dimensional data and clinical statistical tools used to determine the utility of the interpreted data. This review summarizes each of these steps, with the goal of providing the nonstatistician proteomics researcher with a working understanding of the various approaches that may be used by statisticians. Emphasis is placed on the process of mining high-dimensional data to identify a specific set of biomarkers that may be used in a diagnostic or other assay setting.


Inhibitory effect of polaprezinc on the inflammatory response to Helicobacter pylori.
Helicobacter pylori-infected gastrointestinal mucosa is frequently infiltrated by polymorphonuclear leukocytes (PMN) and monocytes, and these invading cells have been implicated in gastrointestinal mucosal inflammation. To clarify the efficacy of polaprezinc, a chelate compound consisting of zinc and L-carnosine, against H pylori-induced inflammation including PMN infiltration, the in vitro effects of this drug on interleukin (IL)-8 production by an established gastric cancer cell line (MKN 45 cells) and on PMN-endothelial cell adhesive interactions was investigated. Polaprezinc and zinc sulphate inhibited IL-8 production by MKN 45 cells in response to stimulation with H pylori water extract (HPE) in a dose-dependent manner from 10(-7) M to 10(-5) M. In addition, the expression of CD11b and CD18 on PMN and PMN-dependent adhesion to endothelial cells elicited by HPE was inhibited by polaprezinc and zinc sulphate in a concentration-dependent manner. L-carnosine did not have any effects on IL-8 production or PMN-endothelial cell interactions. These results suggest that polaprezinc, mainly the zinc component, may inhibit H pylori-induced PMN-mediated gastric inflammation by attenuating CD11b/CD18 expression on PMN and IL-8 production from gastric epithelial cells.


Comparison between intravenous recombinant human erythropoietin and subcutaneous injection in Thai hemodialysis patients.
To compare the efficacy, safety and side effects between subcutaneous and intravenous route of erythropoietin administration in Thai hemodialysis patients. Retrospective study. Retrospective study of hemodialysis patients who switched the route of erythropoietin administration from subcutaneous to intravenous in the Renal Unit Department of Medicine, Bangkok Metropolitan Medical College and Vajira Hospital and Thammasat University was carried out. All patients' information was obtained from the medical records. 60 patients with stable hematocrit level in the last 3 months of the subcutaneous phase who were switched to intravenous route of erythropoietin administration for at least 6 months were recruited The mean hematocrit level of patients in the last 3 months of the subcutaneous period was 30.49+/-4.21%. After switching to the intravenous route for 6 months, the mean hematocrit level was 30.24+/-4.99%. Two patients had to increase the erythropoietin dosage and no side effects were found in the present study. The mean dosage of erythropoietin administered intravenously was not statistically different from the subcutaneous route. There was no correlation between age, sex, cause of renal failure, transferrin saturation, reticulocyte count, C reactive protein and the dosage of erythropoietin, together with the hematocrit level. No other side effects were encountered during the intravenous phase. This study has shown that the subcutaneous erythropoietin in hemodialysis patients can be changed to the intravenous route in the same dosage with good response and stable hematocrit.


The association between the Val158Met polymorphism of the catechol-O-methyl transferase gene and morphological abnormalities of the brain in chronic schizophrenia.
The catechol-O-methyl transferase (COMT) gene is considered to be a promising schizophrenia susceptibility gene. A common functional polymorphism (Val158Met) in the COMT gene affects dopamine regulation in the prefrontal cortex (PFC). Recent studies suggest that this polymorphism contributes to poor prefrontal functions, particularly working memory, in both normal individuals and patients with schizophrenia. However, possible morphological changes underlying such functional impairments remain to be clarified. The aim of this study was to examine whether the Val158Met polymorphism of the COMT gene has an impact on brain morphology in normal individuals and patients with schizophrenia. The Val158Met COMT genotype was obtained for 76 healthy controls and 47 schizophrenics. The diagnostic effects, the effects of COMT genotype and the genotype-diagnosis interaction on brain morphology were evaluated by using a voxel-by-voxel statistical analysis for high-resolution MRI, a tensor-based morphometry. Patients with schizophrenia demonstrated a significant reduction of volumes in the limbic and paralimbic systems, neocortical areas and the subcortical regions. Individuals homozygous for the Val-COMT allele demonstrated significant reduction of volumes in the left anterior cingulate cortex (ACC) and the right middle temporal gyrus (MTG) compared to Met-COMT carriers. Significant genotype-diagnosis interaction effects on brain morphology were noted in the left ACC, the left parahippocampal gyrus and the left amygdala-uncus. No significant genotype effects or genotype-diagnosis interaction effects on morphology in the dorsolateral PFC (DLPFC) were found. In the control group, no significant genotype effects on brain morphology were found. Schizophrenics homozygous for the Val-COMT showed a significant reduction of volumes in the bilateral ACC, left amygdala-uncus, right MTG and left thalamus compared to Met-COMT schizophrenics. Our findings suggest that the Val158Met polymorphism of the COMT gene might contribute to morphological abnormalities in schizophrenia.


Quality appraisal of clinical guidelines for recurrent urinary tract infections using AGREE II: a systematic review.
Recommendations for preventing and diagnosing recurrent urinary tract infection (UTI) tend to vary between clinical practice guidelines (CPGs) because of low-quality scientific evidence, potentially leading to practice variation and suboptimal care. We assessed the quality of existing CPGs for recurrent UTI. A systematic search was performed from January 2000 to June 2021 in PubMed and EMBASE for CPGs on recurrent UTI prevention or hospital diagnostics in Dutch, English, and Spanish. Each CPG was assessed by four appraisers in a multidisciplinary review team, using the Appraisal of Guidelines, Research, and Evaluation II (AGREE II) instrument. We identified and assessed eight CPGs published between 2013 and 2021. The scope and purpose (mean and standard deviation: 67.3 ± 21.8) and clarity of presentation (74.8 ± 17.6) domains scored highly. However, issues with methods, patient participation, conflict of interests, and facilitators and barriers were common and resulted in lower scores for the rigour of development (56.9 ± 25.9), applicability (19.6 ± 23.4), stakeholder involvement (50.4 ± 24.6), and editorial independence (62.1 ± 23.1) domains. Overall, two CPGs were recommended, three were recommended with modifications, and three were not recommended. Significant room for improvement exists in the quality of CPGs for recurrent UTI, with most displaying serious limitations in the stakeholder involvement, rigour of development, and applicability domains. These aspects must be improved to decrease diagnostic and therapeutic uncertainty. Developers could benefit from using checklists and following guidelines when developing de novo CPGs.


Primary ventricular fibrillation complicating acute myocardial infarction: an assessment of predictability and prognosis.
In order to identify patients with a high risk of developing primary ventricular fibrillation (PVF) following acute myocardial infarction (AMI) and to examine the prognostic significance of this arrhythmia, 46 patients who developed PVF were compared to a group of 80 patients who had AMI without PVF. A computerized, multivariate discriminant analysis identified several significant correlates of PVF. Higher rates of hypokalemia, complete left bundle branch block, 3rd-degree AV block and a lower frequency of diabetes were found in the PVF group. No difference was found with respect to the frequency of warning arrhythmias. A discriminant function constructed on the basis of the significant variables had a 4.3% false-negative rate in predicting PVF. Recurrent ventricular fibrillation occurred in nine patients, four of whom died. In-hospital mortality was significantly higher in the PVF than in the control group. As PVF is associated, in part, with treatable derangements and increased mortality, every endeavor should be made to prevent its occurrence.


Health beliefs and barriers related to HIV prevention and screening among students of the University of Vlora: a cross-sectional study.
Previous researchers have found that young university students can have a high level of knowledge about HIV/AIDS infection, but they are still not utilizing the existing HIV prevention methods. As a result there is a need to determine which factors and barriers influence the use of existing HIV screening and prevention methods among students of the University of Vlora in Albania. This was a cross-sectional study conducted among university students in the district of Vlora, Albania from April to June 2018. Stratified, multi-stage sampling technique was used to select randomly study subjects. A structured, self-administered questionnaire was used for data collection. Bivariate and multivariate logistic regression analysis was employed to reflect the relationship between variables. The mean age of the participants (710) was 20.85 ± 2.1 years. 38% of them believe that chances of getting HIV would not stop them to have sexual intercourse with more than one partner, 69% report that using a condom seems like an insult to their partner. 78% of the students with sexual experience didn't used Voluntary Counseling and Testing services. The students from the rural area (AOR = 0.50, 95% CI [0.30-0.82]) and those of first academic year (AOR second/first year =2.31, 95% CI [1.33-3.99], AOR third/first year =1.18, 95% CI [0.65-2.13]) were less likely to use HIV service. The findings reveal that health beliefs and barriers are good predictors of the preventive behaviours toward HIV infection. The survey has provided evidence to suggest that creating awareness about HIV prevention among student community, especially those from non-health sciences and rural areas could contribute to increased uptake of the VCT services, the condom use and to reduce the identified stigmatizing barriers.


Tuberculosis attributed to household contacts in the Philippines.
Data on the burden of disease from tuberculosis (TB) in Filipino households are limited. To determine the magnitude of undiagnosed TB in TB households, and the demographic and socio-economic factors associated with TB in the Philippines, household contacts of adult smear-positive TB patients seen from July 2001 to June 2003 were assessed based on interview, chest X-ray, tuberculin skin test and sputum examination. History of TB and older age were independently associated with TB disease, and age and duration of cohabitation with TB infection. TB and TB infection are highly prevalent in TB households in the Philippines.


Comparisons and Intercorrelations of Physical Performance Variables of Operational Preparedness in Special Operations Forces.
Marine Forces Special Operations Command (MARSOC) deploys teams of operators (OP) and enablers (EN) to accomplish special operations missions. OP and EN are required to train and deploy together to accomplish these missions; however, they have different training and selection pipelines. Advanced strength and conditioning training strategies are applied to both OP and EN to enhance physical preparedness; however, it is unclear how the selection pipeline of these two personnel types affects overall physical preparedness and the relationships between performance variables. The purpose of this study is to gain a greater understanding of the relationships of a wide array of physical preparedness variables in OP and EN in an effort to streamline testing and training strategies. For this study, 155 male (82 OP, 73 EN) MARSOC personnel (age: 29.5 ± 4.9 years, mass: 87.9 ± 11.1 kg, height: 1.79 ± 0.07 m) completed a physical preparedness assessment that included a DEXA assessment of body composition (BF%), 27.4 m sprint (30 yd), countermovement jump (VJ), 5-10-5 pro-agility (Agility), medicine ball toss (UBP), isometric mid-thigh pull (IMTP), and a 30 second (AnC) and 5 minute (AC) non-motorized treadmill run. Independent samples t tests, Mann-Whitney U tests, and Spearman's Rank correlations were used to compare variables between OP and EN. OP demonstrated greater VJ, UBP, IMTP, AnC, and AC (P < 0.05); and significantly lower BF% and agility time (P < 0.05). Measurements of mass, height, body mass index, and 30 yd were not significantly different (P > 0.05). Weak to moderate correlations were seen between anthropometric and performance variables. OP and EN demonstrated similar correlations for most performance and anthropometric variables. These results suggest that MARSOC OP demonstrate better physical preparedness over EN, while similar trends are observed between performance variables. Tests with moderate to high correlations may be removed from the protocol to account for testing time constraints. Height, weight, and BF% variables are poorly correlated with performance, particularly in OP, questioning their value in physical performance assessments in this population.


Ovarian abscess from Salmonella: a case report.
An ovarian site of Salmonella bacteremia is rare. The contents of a teratoma may hide the organisms easily. Clinicians should be alert to this possibility when the patient had a teratoma with Salmonella infection. A 19-year-old woman presented with a missed menstrual period. An adnexal mass was found during a routine gynecologic examination. The patient had had gastroenteritis 2 months earlier but did not complain of a gastrointestinal problem at presentation. Exploratory laparotomy was performed for a suspected ovarian tumor. An infective teratoma was considered, but the infection source was unknown until the culture report showed a Salmonella infection. Salmonella infection is a self-limiting, febrile disease and is unlikely to involve organs other than the gut. A nontyphoid ovarian abscess became a rare late complication of acute gastroenteritis. Clinicians should pay special attention to the differential diagnosis of ovarian tumor in patients with a history of Salmonella infection, especially those with such ovarian lesions as endometrioma or teratoma and with recent abdominal pain, as noted in this case.


Augmentation of arginase Ⅱ expression in the human endometrial epithelium in the secretory phase.
L-arginine is the common substrate for arginase and nitric oxide synthase (NOS). Arginase converts L-arginine to urea and L-ornithine. L-Ornithine is the principal precursor for the production of polyamines and L-proline, which are required for cell proliferation and collagen synthesis. Endothelial NOS is expressed in the human endometrial glandular epithelium, but the expression and physiological roles of arginase in the human endometrium are not clear. The objective of this study was to investigate the expression and distribution patterns of arginases Ⅰ (A-Ⅰ) and Ⅱ (A-Ⅱ) in the human endometrium by using immunohistochemistry, reverse transcription-polymerase chain reaction (RTPCR), and western blotting. A-Ⅰ and A-Ⅱ were detected by immunohistochemistry in human endometrial epithelial cells during the proliferative and secretory phases of the menstrual cycle. RT-PCR showed that A-Ⅰ and A-Ⅱ mRNA were expressed in human endometrial tissue. Western blotting analysis results showed the expression of A-Ⅱ protein. Immunohistochemistry and western blotting results showed that expression levels of A-Ⅱ were significantly higher in the secretory phase than in the proliferative phase. Increased A-Ⅱ levels in the secretory phase may be responsible for endometrial growth by increasing polyamines and proline products.


Improving sudden unexplained infant death investigation practices: an evaluation of the Centers for Disease Control and Prevention's SUID Investigation Training Academies.
Lack of thorough sudden unexplained infant death investigations (SUIDIs) has hindered accurate cause-of-death determination, infant mortality surveillance, and prevention strategies. To standardize SUIDI practices, the Centers for Disease Control and Prevention created a reporting form, guidelines, training curriculum, and SUIDI Training Academies using a train-the-trainer format. The training goal was to train teams of five in each state, who would reach an additional 1250 participants.The aim of this study is to evaluate the SUIDI Training Academies by determining professional characteristics of participants, assessing the level of confidence in infant death investigation components, enumerating the number of secondary trainings, and discussing recommendations for future trainings.To evaluate the training and the success of the train-the-trainer strategy, we used training evaluations, participant lists, and Web-based training logs to assess participant knowledge, skills, perceptions, and characteristics and number of secondary trainings.We trained 270 trainers at 5 SUIDI Training Academies. Greater than 96% of respondents reported confidence in case investigation skills and reported that hands-on laboratory sessions facilitated the practice of new skills. Academy trainers have trained greater than 23,000 medicolegal professionals, exceeding the training goal. This evaluation allowed us to identify opportunities to improve future SUIDI trainings.


Evaluation of functional relationship between mouse hippocampal cholinergic and nitrergic systems in anxiogenic-like behavior.
Although a body of evidence shows the crucial role of hippocampal nitrergic and cholinergic systems in the modulation of anxiety, little is known about their functional relationship with regard to anxiety. The present study investigated the relationship between intra-CA1 administration of a nicotinic acetylcholine receptor antagonist (mecamylamine) and a nitric oxide synthase inhibitor [Nω-nitro-L-arginine methyl ester (L-NAME)] or its precursor (L-arginine) in anxiety-related behaviors. Mice received bilateral intra-CA1 injections of either L-NAME or L-arginine in the presence of mecamylamine and were subsequently tested in the elevated plus maze. A dose of 0.5 μg/0.5 μl mecamylamine bilaterally administered into CA1 did not change the percentage of open arm time (%OAT) or the percentage of open arm entries (%OAE) in the elevated plus maze task and thus was considered as a subeffective dose. Intra-CA1 administration of either L-arginine (1 and 1.5 μg/0.5 μl, bilaterally) or L-NAME (at 60 ng/0.5 μl, bilaterally) decreased %OAT, which represents an anxiogenic-like effect. Coadministration of the subeffective dose of mecamylamine together with the lower doses of L-NAME (10 and 30 ng/0.5 μl, bilaterally) or L-arginine (0.5 μg/0.5 μl, bilaterally) led to a decrease in %OAT and %OAE. Thus, both L-NAME and L-arginine showed anxiogenic-like effects, but the effects of mecamylamine were too small to support a functional relationship between the hippocampal cholinergic and nitrergic systems.


Conjugation of the ubiquitin-like protein NEDD8 to cullin-2 is linked to von Hippel-Lindau tumor suppressor function.
The von Hippel-Lindau tumor suppressor protein pVHL assembles with cullin-2 (hCUL-2) and elongin B/C forming a protein complex, CBCVHL, that resembles SKP1-CDC53-F-box protein ubiquitin ligases. Here, we show that hCUL-2 is modified by the conserved ubiquitin-like protein NEDD8 and that NEDD8-hCUL-2 conjugates are part of CBCVHL complexes in vivo. Remarkably, the formation of these conjugates is stimulated by the pVHL tumor suppressor. A tumorigenic pVHL variant, however, is essentially deficient in this activity. Thus, ligation of NEDD8 to hCUL-2 is linked to pVHL activity and may be important for pVHL tumor suppressor function.


Targeted Therapies in Cancer: To Be or Not to Be, Selective.
Development of targeted therapies in recent years revealed several nonchemotherapeutic options for patients. Chief among targeted therapies is small molecule kinase inhibitors targeting key oncogenic signaling proteins. Through competitive and noncompetitive inhibition of these kinases, and therefore the pathways they activate, cancers can be slowed or completely eradicated, leading to partial or complete remissions for many cancer types. Unfortunately, for many patients, resistance to targeted therapies, such as kinase inhibitors, ultimately develops and can necessitate multiple lines of treatment. Drug resistance can either be de novo or acquired after months or years of drug exposure. Since resistance can be due to several unique mechanisms, there is no one-size-fits-all solution to this problem. However, combinations that target complimentary pathways or potential escape mechanisms appear to be more effective than sequential therapy. Combinations of single kinase inhibitors or alternately multikinase inhibitor drugs could be used to achieve this goal. Understanding how to efficiently target cancer cells and overcome resistance to prior lines of therapy became imperative to the success of cancer treatment. Due to the complexity of cancer, effective treatment options in the future will likely require mixing and matching these approaches in different cancer types and different disease stages.


Asynchronous vowel-pair identification across the adult life span for monaural and dichotic presentations.
Temporal order abilities decrease with age. Declining temporal processing abilities may influence the identification of rapid vowel sequences. Identification patterns for asynchronous vowel pairs were explored across the life span. Young, middle-aged, and older listeners completed temporal order tasks for pairs of 70-ms and 40-ms vowel stimuli. For a given vowel duration, naturally spoken vowels were equated for duration, intensity, and fundamental frequency. Listeners completed monaural and dichotic temporal order tasks that involved identifying the vowel pair in the correct order. The stimulus onset asynchrony that yielded 50% accuracy for identifying the vowel pair in the correct order was used to equate performance among listeners. Vowel identification response patterns were determined at this stimulus onset asynchrony threshold. Vowel identification patterns were largely consistent across age groups. Older listeners were influenced by the order of certain vowel pairs. Not all vowel pairs were identified equally well. Vowel dominance patterns were also observed, with /a/ being identified most accurately for the vowel pairs tested. Formant dynamics explained, in part, identification and confusion patterns. Vowel identification accuracy patterns were reasonably similar across the life span, regardless of presentation mode, vowel duration, or effect of considerable stimulus exposure. Large effects of vowel order were observed, particularly for older listeners.


Transfer Learning Effects of Biofeedback Running Retraining in Untrained Conditions.
Running gait retraining via peak tibial shock biofeedback has been previously shown to reduce impact loading and mitigate running-related symptoms. In previous research, peak tibial shock is typically measured and trained for one limb at a single constant training speed during all training sessions. The goal of this study was to determine how runners transfer learning in the trained limb to the untrained limb at different unconstrained speeds. Thirteen runners (3 females, age = 41.1 ± 6.9 yr, running experience = 6.8 ± 4.4 yr, weekly running distance = 30.7 ± 22.2 km) underwent running gait biofeedback retraining via continuous tibial acceleration measured at the right distal tibia. Before and after the training, participants were asked to run at their self-selected constrained training speeds (2.8 ± 0.2 m·s) and at 110% and 90% of the training speed. Pretraining and posttraining peak tibial shock values for each limb were compared. Participants reduced peak tibial shock in the trained limb by 35% to 37% (P < 0.05, Cohen's d = 0.78-0.85), and in the untrained limb by 20% to 23% (P < 0.05, Cohen's d = 0.51-0.71) across the three testing speeds. The reduction was not significantly different between the trained and untrained limbs (P = 0.31-0.79, Cohen's d = 0.18-0.45). Similarly, there was no difference in peak tibial shock reduction among the three running speeds (P = 0.48-0.61, Cohen's d = 0.06-0.45). Participants demonstrated transfer learning effects evidenced by concomitant reduced peak tibial shock in the untrained limb, and the learning effects were retrained when running at a 10% variance of the training speed.


Molecular characterization of Hepatitis C virus 3a in Peshawar.
The purpose of this study was to explore molecular epidemiology of HCV genotype 3a in Peshawar based on sequencing and phylogenetic analysis of Core region of HCV genome. Chronically infected Hepatitis C virus infected patients enrolled under the Prime Minister Hepatitis C control program at three Tertiary care units of Peshawar [Khyber Teaching Hospital Peshawar, Lady Reading Hospital Peshawar, Hayat Abad Medical Complex Peshawar] were included in this cross sectional observational study. Qualitative detection of HCV and HCV genotyping was carried out by a modified reverse transcription-polymerase chain reaction (RT-PCR) and type specific genotyping assay. The Core gene of HCV genotype 3a was amplified, cloned and sequenced. The sequences obtained were used for phylogenetic analysis using MEGA 6 software. Among the 422 (82.75 %) PCR positive samples, 192 (45.5 %) were identified as having HCV genotype 3a infection. HCV Core gene sequencing was carried out randomly for the characterization of HCV 3a. Nucleotide sequence analysis of the obtained viral genomic sequences based on partial HCV 3a Core gene sequences with reference sequences from different countries showed that our sequences clustered with some local and regional sequences with high bootstrap values. HCV 3a is highly prevalent in Peshawar, Pakistan and its phylogenetics based on Core gene sequences indicate the prevalence of different lineages of HCV 3a in Peshawar which may have consequences for disease management strategies causing more economic pressure on the impoverished population due to possible antiviral resistance.


[The variants of enteral distress syndrome correction with peritonitis].
To determine the effectiveness of a new treatment regimen for patients with widespread peritonitis with an accent on enteroprotection based on the use of a drug of the metabolic type of action of remaxol and physiotherapy. Clinical and laboratory studies of 82 patients with widespread peritonitis, mainly with grade 2 severity according to the Mannheim peritonitis Index, severe form - according to the ARASNE II scale. In the 1st group (28) patients underwent intraoperative intestinal intubation in the traditional way; in the 2nd (22) - intestinal intubation according to the original method; in the 3rd (32) - intestinal intubation according to the original method and combined use of remaxol (parenterally, enterally and intraperitoneally). An intestinal tube of an original design was used, which allows electrical stimulation of the duodenum in the postoperative period. The study evaluates clinical data, the results of instrumental and laboratory studies: ultrasound examination of the abdominal cavity, assessment of the functional state of the small intestine, a number of indicators of homeostasis. It was shown that in patients with acute widespread peritonitis who underwent intestinal intubation according to the original method (group 2), as well as in combination with remaxol (group 3), the postoperative period was relatively more favorable. One of the factors optimizing the course of the disease was the relatively rapid restoration of the structural and functional state of the small intestine due to its electrical stimulation. The clinical and laboratory positive effect was especially significant in the 3rd group of patients, in which the use of remaxol, which has a membrane-stabilizing effect, played a special role in the enteroprotective effect. Timely correction of enteral distress syndrome resulted in a significant decrease in the severity of the syndrome of endogenous intoxication and oxidative stress, which was important in significantly improving the results of treatment of patients. The use of technical innovations in the form of an original nasointestinal tube, which allows to quickly restore intestinal motility due to electrical stimulation, as well as the use of remaxol (parenterally, enterally and intraperitoneally) significantly optimize the course of the early postoperative period of patients with acute widespread peritonitis.


The assault on your financials.
Hospital executives are confronting what may be unprecedented pressure on their bottom lines as forces converge from all directions: Medicare cuts brought on by the Balanced Budget Amendment, slow pays and denial of claims by managed care plans, the staggering cost of new technology, and big increases in pharmaceutical costs.


Purification and characterization of a new GTP-binding protein of Mr 24,000 in bovine brain membranes.
A GTP-binding protein with an Mr of 24,000 was purified from a cholate extract of bovine brain membranes in addition to the previously reported alpha beta gamma-trimeric GTP-binding proteins (G proteins). Partial amino acid sequence analysis of the purified 24-kDa protein revealed that it was not identical to any of the low Mr GTP-binding proteins already reported, but similar to the rac-gene products serving as the substrate of an ADP-ribosyltransferase (C3) purified from the culture medium of Clostridium botulinum type C. However, the 24-kDa protein was not ADP-ribosylated by the botulinum C3 enzyme. The 24-kDa protein was purified as a nucleotide-free form and characterized by the following unique properties distinct from those of alpha beta gamma-trimeric G proteins. (1) Mg2+ was essentially required for nucleotide binding to the 24-kDa protein; there was a progressive increase in its binding affinity for nucleotides as the concentration of the divalent cation was increased. (2) Nucleotides previously bound to the 24-kDa protein were rapidly dissociated from the protein in Mg(2+)-free medium, in accord with the fact that the protein was indeed purified as a nucleotide-free form with Mg(2+)-free solutions. (3) The 24-kDa protein apparently exhibited much lower GTPase activity than do alpha beta gamma-trimeric G proteins because the product GDP was released from the 24-kDa protein in exchange for the substrate GTP only at a very low rate. Based on these findings, a possible role of the 24-kDa protein in cellular signalling is discussed in comparison with well characterized alpha beta gamma-trimeric G proteins.


Pain in acute and chronic wounds: a descriptive study.
The significance of pain in wound healing is much neglected because of biases against pain management in general, a lack of knowledge of available analgesics, and difficulties associated with pain measurement. To assess pain in patients suffering from acute and chronic wounds, a 1-day descriptive study was conducted involving 50 patients, 26 with acute wounds and 24 with chronic wounds, served by the wound clinic of a university hospital. Patients responded to questions regarding onset, location, type, and intensity of pain using the Visual Analog and Visual Reporting Scales and to statements about aggravating and relieving factors and overall impact on their quality of life using a 5-point scale where 5 = totally agree and 1 = completely disagree. Results showed pain was commonly mild to moderate (41 patients, 88%), located in and around wound (43 patients, 93.5%), occurred most frequently during dressing change (30 patients, 65%), and was relieved by medications (39 patients, 84.8%) and positioning (17 patients, 37%). The most commonly affected quality of life variables were physical activity (40 patients, 87% of patients) and social functioning (23 patients, 50%). Controlling wound pain can play a major role in improving patient quality of life.


Preoperative Use of Alpha-1 Receptor Blockers in Male Patients Undergoing Extracorporeal Shock Wave Lithotripsy for a Ureteral Calculus.
In this retrospective single-center cohort study, we investigated the impact of preoperative use of an alpha-1 adrenergic receptor (AR) blocker on the outcome of single-session extracorporeal shock wave lithotripsy (SWL) in 193 male patients who underwent SWL for a single ureteral calculus between 2006 and 2016. We reviewed their medical records to obtain the data on the preoperative use of alpha-1 AR blockers. The primary outcome was treatment success after single-session SWL. We performed a multivariable logistic regression analysis adjusting for clinically important confounders to examine the association between preoperative use of alpha-1 AR blockers and the treatment success of SWL. Among the 193 patients, 15 (7.8%) were taking an alpha-1 AR blocker preoperatively. A multivariable analysis showed that preoperative use of an alpha-1 AR blocker was a significant negative predictor for treatment success of SWL (adjusted odds ratio 0.17; 95% confidence intervals, 0.04-0.74). Our findings suggest that the preoperative use of an alpha-1 AR blocker was a negative predictor of treatment success of SWL in male patients with a single ureteral calculus. Clinicians should pay more attention to the preoperative drug use in determining an appropriate stone therapy modality.


Perceived health from biological motion predicts voting behaviour.
Body motion signals socially relevant traits like the sex, age, and even the genetic quality of actors and may therefore facilitate various social judgements. By examining ratings and voting decisions based solely on body motion of political candidates, we considered how the candidates' motion affected people's judgements and voting behaviour. In two experiments, participants viewed stick figure motion displays made from videos of politicians in public debate. Participants rated the motion displays for a variety of social traits and then indicated their vote preference. In both experiments, perceived physical health was the single best predictor of vote choice, and no two-factor model produced significant improvement. Notably, although attractiveness and leadership correlated with voting behaviour, neither provided additional explanatory power to a single-factor model of health alone. Our results demonstrate for the first time that motion can produce systematic vote preferences.


Non-synonymous SNP in the ApoR gene associated with pork meat quality.
Two novel non-synonymous SNPs in the 2nd and 3rd exons of the porcine ApoR gene are reported. One was identified as a novel SNP significantly associated with multiple traits of pork meat quality. The data can provide a useful resource for developing a marker in the genetic improvement of pigs.


Effect of low grade radiofrequency heating on arterial vasospasm in the porcine model.
Nineteen pigs were studied in order to assess the effect of low grade, radiofrequency-powered, thermal balloon angioplasty on the vasoconstrictor response of peripheral arteries. A mechanical stimulus was used to induce vasospasm. Thermal angioplasty reduced the extent of inducible vasospasm from 79% to 6% compared to nonthermal control inflations, which reduced the vasoconstrictor response from 75% to 60% (P < 0.001). Histologic studies demonstrated that the extent of myocyte necrosis was significantly greater in the thermally treated arteries than in the control vessels (P < 0.01). Thermal balloon angioplasty at 60 degrees C significantly attenuates peripheral arterial vasospasm induced by mechanical trauma in the porcine model. This paralytic effect may be related to the loss of myocytes secondary to thermal necrosis.


[Role of anidulafungin in critically ill patients].
The most frequent invasive fungal infections in critically ill patients are invasive candidiasis, among which is candidemia. In the last few years, these infections have become more common in intensive care units (ICU), including those produced by species other than Candida albicans. This phenomenon may lead to the development of species resistant to antifungal agents. To start the most appropriate treatment, early diagnosis of the infection is essential, which would reduce empirical antibiotic treatment and increase the proportion of advanced or directed antibiotic therapy. Given the poor reliability of the available diagnostic techniques, new strategies are currently being employed in the ICU, such as the use of scores to evaluate the presence of fungal infections. The therapeutic arsenal against these infections has been increased and the introduction of anidulafungin represents the addition of a highly appropriate drug for the treatment of invasive candidiasis in immunocompetent critically ill patients.