Familial partial lipodystrophy presenting as metabolic syndrome.
We report the first described case of a heterozygous p.R545H (c.1634 G > A) missense mutation in the LMNA gene with clinical features compatible with Dunnigan-type 2 familial partial lipodystrophy (FPLD2). The case presented as metabolic syndrome to a specialist clinical service and highlights the overlap between FPLD2 and the metabolic syndrome. The associations with type 2 diabetes mellitus, fatty liver disease, polycystic ovarian syndrome, and hypertriglyceridemia are highlighted. The importance of evaluating patients for these associated conditions is discussed, and the potential mechanisms of disease are briefly outlined. The mutation has been previously reported in a heart failure database without a clinical description. The links between heart failure and the clinical condition are briefly considered.


Hepatitis C virus NS3 protease is activated by low concentrations of protease inhibitors.
The nonstructural protein 3 (NS3) of hepatitis C virus (HCV) is a bifunctional enzyme with a protease and a helicase functionality located in each of the two domains of the single peptide chain. There is little experimental evidence for a functional role of this unexpected arrangement since artificial single domain forms of both enzymes are catalytically competent. We have observed that low concentrations of certain protease inhibitors activate the protease of full-length NS3 from HCV genotype 1a with up to 100%, depending on the preincubation time and the inhibitor used. The activation was reduced, but not eliminated, by increased ionic strength, lowered glycerol concentration, or lowered pH. In all cases, it was at the expense of a significant loss of activity. Activation was not seen with the artificial protease domain of genotype 1b NS3 fused with a fragment of the NS4A cofactor. This truncated and covalently modified enzyme form was much less active and exhibited fundamentally different catalytic properties to the full-length NS3 protease without the fused cofactor. The most plausible explanation for the activation was found to involve a slow transition between two enzyme conformations, which differed in their catalytic ability and affinity for inhibitors. Equations derived based on this assumption resulted in better fits to the experimental data than the equation for simple competitive inhibition. The mechanism may involve an inhibitor-induced stabilization of the helicase domain in a conformation that enhances the protease activity, or an improved alignment of the catalytic triad in the protease. The proposed mnemonic mechanism and derived equations are viable for both these explanations and can serve as a basic framework for future studies of enzymes activated by inhibitors or other ligands.


Synthesis of Free-Standing Flexible rGO/MWCNT Films for Symmetric Supercapacitor Application.
Herein, we report a novel, simple, and cost-effective way to synthesize flexible and conductive rGO and rGO/MWCNT freestanding films. The effects of MWCNT addition on the electrochemical performance of rGO/MWCNT nanocomposite films are investigated in some strong base aqueous electrolytes, such as KOH, LiOH, and NaOH via three-electrode system. The supercapacitor behavior of the films is probed via cyclic voltammetry, galvanostatic charging-discharging, and electrochemical impedance spectroscopy. The structural and morphological studies of the films are performed by X-ray diffractometer, Raman spectrometer, surface area analyzer, thermogravimetric analysis, field emission scanning electron microscope and transmission electron microscope. The rGO/MWCNT film synthesized with 10 wt% MWCNTs (GP10C) exhibits high specific capacitance of 200 Fg-1, excellent cyclic stability with 92% retention after 15,000 long cycle test, small relaxation time constant (~ 194 ms), and high diffusion coefficient (7.8457 × 10-9 cm2 s-1) in 2 M KOH electrolyte. Furthermore, the symmetric supercapacitor coin cell with GP10C as both anode and cathode using 2 M KOH as electrolyte demonstrates high energy density of 29.4 Whkg-1 and power density of 439 Wkg-1 at current density 0.1 Ag-1 and good cyclic stability with 85% retention of the initial capacitance at 0.3 Ag-1 after 10,000 cycles. Such a high performance of the GP10C film in the supercapacitor can be ascribed to the large surface area and small hydration sphere radius and high ionic conductivity of K+ cations in KOH electrolyte.


Pulmonary effects of short term selenium deficiency.
Selenium dependent glutathione peroxidase (GPx) reduces hydrogen peroxide (H2O2) and organic hydrogen peroxides in both normal and pathological states. Chronic dietary deficiency of selenium results in a gradual decrease in GPx and altered response to environmental stress. However, glutathione-S-transferase (GST) isozymes may increase and compensate for chronic GPx deficiency. The pattern of antioxidant enzyme activity and immunolocalisation of various enzymes in rat lung has not been described in short term (< 3 weeks) acute selenium deficiency. The time course of GPx depletion from rat lung (measured every five days in subgroups of rats) during acute dietary selenium deficiency was evaluated. After 20 days of depletion, enzyme activity of lung GPx, catalase, superoxide dismutase (SOD), glutathione reductase (GR), glucose-6-phosphodiesterase (G-6-PD), and GST were determined. Immunohistochemical localisation of GPx and SOD was also performed. The response to lethal hyperoxia (> 95%) in control and selenium deficient rats was then established. At 20 days, lung GPx activity in the rats fed a selenium deficient diet was one third less than in control animals who received a normal diet, while changes in blood enzymes between control and deficient animals were similar. Other lung enzyme activities remained normal with the exception of cyanide inhibited SOD activity measured in selenium deficient rat lungs which declined to approximately 50% of normal. Immunohistochemical localisation of GPx showed a generalised loss of the enzyme throughout the lung parenchyma with some possible sparing of activity in epithelial cells of the bronchioles. When exposed to lethal hyperoxia, selenium deficient animals were more susceptible than control rats. This is the earliest time at which dietary selenium deficiency has been shown to produce moderate loss of GPx activity. This change in activity was associated with increased susceptibility to pulmonary oxidant stress. However, the role of decreased SOD activity (presumed to represent copper, zinc SOD), although unexpected, may have been a major contributor to increased damage from hyperoxia. These results emphasise the complex potential interaction of elemental deficiency with the natural antioxidant response to lethal hyperoxia.


The inhibitory effect of serum from hairy-cell leukaemia patients on normal progenitor cells may disappear following prolonged treatment with alpha-interferon.
The possibility that serum from hairy-cell leukaemia (HCL) patients at diagnosis may show an inhibitory effect on the in vitro colony growth of normal haemopoietic progenitor cells has been suggested. Several studies have documented the efficacy of alpha-Interferon (alpha-IFN) in inducing a complete restoration of peripheral blood values and, in some cases, a complete clinical remission. In this study we have evaluated the regulatory effect of serum, collected before and after 3 and 12 months of alpha-IFN treatment, from 10 patients with untreated HCL, on the in vitro growth of normal bone marrow CFU-GM, BFU-E and CFU-MK. The effect of conditioned media, prepared from enriched hairy cells (HC) cultured in synthetic medium, on the growth of normal haemopoietic progenitors was also investigated. The results obtained confirm that sera from untreated HCL patients display a variable degree of inhibitory activity in the progenitor cell compartments analysed. Disappearance of the inhibitory activity, particularly evident for the erythroid compartment, was found only in patients who displayed a disappearance of circulating HC and a good haematological response after prolonged (12 months) treatment with alpha-IFN. The possibility that the serum of patients with HCL may contain a haemopoietic inhibitory factor, released by the neoplastic HC population, is suggested.


Association of busulfan exposure with survival and toxicity after haemopoietic cell transplantation in children and young adults: a multicentre, retrospective cohort analysis.
Intravenous busulfan combined with therapeutic drug monitoring to guide dosing improves outcomes after allogeneic haemopoietic cell transplantation (HCT). The best method to estimate busulfan exposure and optimum exposure in children or young adults remains unclear. We therefore assessed three approaches to estimate intravenous busulfan exposure (expressed as cumulative area under the curve [AUC]) and associated busulfan AUC with clinical outcomes in children or young adults undergoing allogeneic HCT. In this retrospective analysis, patients from 15 centres in the Netherlands, USA, Canada, Switzerland, UK, Italy, Germany, and Australia who received a busulfan-based conditioning regimen between March 18, 2001, and Feb 12, 2015, were included. Cumulative AUC was calculated by numerical integration using non-linear mixed effect modelling (AUCNONMEM), non-compartmental analysis (AUC from 0 to infinity [AUC0-∞] and to the next dose [AUC0-τ]), and by individual centres using various approaches (AUCcentre). The main outcome of interest was event-free survival. Other outcomes of interest were graft failure or relapse, or both; transplantation-related mortality; acute toxicity (veno-occlusive disease or acute graft versus-host disease [GvHD]); chronic GvHD; overall survival; and chronic-GvHD-free event-free survival. We used propensity-score-adjusted Cox proportional hazard models, Weibull models, and Fine-Gray competing risk regressions for statistical analyses. 790 patients were enrolled, 674 of whom were included: 274 (41%) with malignant and 400 (59%) with non-malignant disease. Median age was 4·5 years (IQR 1·4-10·7). The median busulfan AUCNONMEM was 74·4 mg × h/L (95% CI 31·1-104·6), which correlated with the standardised method AUC0-∞ (r2=0·74), but the latter correlated poorly with AUCcentre (r2=0·35). Estimated 2-year event-free survival was 69·7% (95% CI 66·2-73·0). Event-free survival at 2 years was 77·0% (95% CI 72·1-82·9) in the 257 patients with an optimum intravenous busulfan AUC of 78-101 mg × h/L compared with 66·1% (60·9-71·4) in the 235 patients at the low historical target of 58-86 mg × h/L and 49·5% (29·2-66·0) in the 44 patients with a high (>101 mg × h/L) busulfan AUC (p=0·011). Compared with the low AUC group, graft failure or relapse occurred less frequently in the optimum AUC group (hazard ratio [HR] 0·57, 95% CI 0·39-0·84; p=0·0041). Acute toxicity (HR 1·69, 1·12-2·57; p=0·013) and transplantation-related mortality (2·99, 1·82-4·92; p<0·0001) were significantly higher in the high AUC group (>101 mg × h/L) than in the low AUC group (<78 mg × h/L), independent of indication; no difference was noted between AUC groups for chronic GvHD (<78 mg × h/L vs ≥78 mg × h/L, HR 1·30, 95% CI 0·73-2·33; p=0·37). Improved clinical outcomes are likely to be achieved by targeting the busulfan AUC to 78-101 mg × h/L using a new validated pharmacokinetic model for all indications. Research Allocation Program and the UCSF Helen Friller Family Comprehensive Cancer Center and the Mt Zion Health Fund of the University of California, San Francisco.


Endothelial NOS and the blockade of LTP by NOS inhibitors in mice lacking neuronal NOS.
Long-term potentiation (LTP) is a persistent increase in synaptic strength implicated in certain forms of learning and memory. In the CA1 region of the hippocampus, LTP is thought to involve the release of one or more retrograde messengers from the postsynaptic cell that act on the presynaptic terminal to enhance transmitter release. One candidate retrograde messenger is the membrane-permeant gas nitric oxide (NO), which in the brain is released after activation of the neuronal-specific NO synthase isoform (nNOS). To assess the importance of NO in hippocampal synaptic plasticity, LTP was examined in mice where the gene encoding nNOS was disrupted by gene targeting. In nNOS- mice, LTP induced by weak intensity tetanic stimulation was normal except for a slight reduction in comparison to that in wild-type mice and was blocked by NOS inhibitors, just as it was in wild-type mice. Immunocytochemical studies indicate that in the nNOS- mice as in wild-type mice, the endothelial form of NOS (eNOS) is expressed in CA1 neurons. These findings suggest that eNOS, rather than nNOS, generates NO within the postsynaptic cell during LTP.


TENTS guidelines: development of post-disaster psychosocial care guidelines through a Delphi process.
How best to plan and provide psychosocial care following disasters remains keenly debated. To develop evidence-informed post-disaster psychosocial management guidelines. A three-round web-based Delphi process was conducted. One hundred and six experts rated the importance of statements generated from existing evidence using a one to nine scale. Participants reassessed their original scores in the light of others' responses in the subsequent rounds. A total of 80 (72%) of 111 statements achieved consensus for inclusion. The statement 'all responses should provide access to pharmacological assessment and management' did not achieve consensus. The final guidelines recommend that every area has a multi-agency psychosocial care planning group, that responses provide general support, access to social, physical and psychological support and that specific mental health interventions are only provided if indicated by a comprehensive assessment. Trauma-focused cognitive-behavioural therapy (CBT) is recommended for acute stress disorder or acute post-traumatic stress disorder, with other treatments with an evidence base for chronic post-traumatic stress disorder being made available if trauma-focused CBT is not tolerated. The Delphi process allowed a consensus to be achieved in an area where there are limitations to the current evidence.


HaploPOP: a software that improves population assignment by combining markers into haplotypes.
In ecology and forensics, some population assignment techniques use molecular markers to assign individuals to known groups. However, assigning individuals to known populations can be difficult if the level of genetic differentiation among populations is small. Most assignment studies handle independent markers, often by pruning markers in Linkage Disequilibrium (LD), ignoring the information contained in the correlation among markers due to LD. To improve the accuracy of population assignment, we present an algorithm, implemented in the HaploPOP software, that combines markers into haplotypes, without requiring independence. The algorithm is based on the Gain of Informativeness for Assignment that provides a measure to decide if a pair of markers should be combined into haplotypes, or not, in order to improve assignment. Because complete exploration of all possible solutions for constructing haplotypes is computationally prohibitive, our approach uses a greedy algorithm based on windows of fixed sizes. We evaluate the performance of HaploPOP to assign individuals to populations using a split-validation approach. We investigate both simulated SNPs data and dense genotype data from individuals from Spain and Portugal. Our results show that constructing haplotypes with HaploPOP can substantially reduce assignment error. The HaploPOP software is freely available as a command-line software at www.ieg.uu.se/Jakobsson/software/HaploPOP/.


Altered regulation of matrix metalloproteinase-2 in aortic remodeling during aging.
To elucidate potential mechanisms of enhanced type 2 matrix metalloprotease levels and activity within the thickened aged rat aorta, the present study measured its mRNA and protein levels and those of its membrane bound activator, MT1-MMP, its endogenous tissue inhibitor, TIMP-2, tissue type, and urokinase plasminogen activators and their receptors, and an inhibitor of plasminogen activation in aortae from Fisher 344X Brown Norway rats, 2 to 30 months of age. Semiquantitative immunohistochemistry, in situ hybridization, and in situ zymography of aortae detected a marked age-associated increase in gelatinolytic activity of type 2 metalloprotease within the thickened intima, internal elastic lamina, and elastic fibers in the inner part of the thickened tunica media, whereas the intimal tissue inhibitor of metalloprotease-2 mRNA and protein levels were not age related. Both activators of plasminogen and their receptors increased approximately 2-fold within the intima between 2 to 30 months. Similar, but not identical, age-associated changes in factors that regulate protease activity within the aortic media were also observed. We conclude that discordant regulation of factors that determine the activation status of type 2 matrix metalloprotease, coupled with an increase in the expression of its zymogen, occur with aging, which lead to an increase in the amount of activated protease. These factors are candidate mechanisms for age-associated vascular remodeling, a potent risk factor for vascular diseases with advancing age.


The role of protein kinase C in CD8+ T lymphocyte effector responses.
Rare CD8+ T cells present in beta2microglobulin-deficient (beta2m-/-) mice reject allogeneic tumors but not syngeneic wild-type tumors. The lack of syngeneic tumor rejection in vivo is correlated with a partial response of beta2m-/- CD8+ cell lines to syngeneic tumor cells in vitro. This partial response is characterized by perforin/granzyme-mediated cytolytic activity in the absence of cytokine secretion or proliferation. Allogeneic tumors induce cytolysis, cytokine secretion, and proliferation. Cytokine secretion may therefore be an important effector mechanism for tumor rejection by CD8+ T cells. To determine the missing signaling events needed for cytokine secretion as well as the events inducing the isolated cytotoxic response, we attempted to restore cytokine secretion of beta2m-/- CD8+ cells to syngeneic MHC class I. Phorbol ester and syngeneic tumor cells acted synergistically to induce full responsiveness of beta2m-/- CD8+ cells. However, this synergistic induction of cytokine secretion used a different pathway than that induced by alloantigen. Protein kinase C (PKC) inhibitor prevented the syngeneic class I plus PMA-induced cytokine secretion, but not allo-class I-induced cytokine secretion. In contrast to the PKC independent alloantigen-induced cytokine secretion, cytolysis of both allogeneic and syngeneic targets was PKC dependent. The differential dependence of effector functions on PKC activation was also found in beta2m+/+ CD8+ T cells. Thus, two distinct signaling pathways (PKC dependent and PKC independent) may ultimately converge to induce cytokine secretion in CD8+ cells. The TCR engagement-initiated pathway is PKC independent, whereas the phorbol ester-activated pathway is PKC dependent.


How reliable are clinical systems in the UK NHS? A study of seven NHS organisations.
It is well known that many healthcare systems have poor reliability; however, the size and pervasiveness of this problem and its impact has not been systematically established in the UK. The authors studied four clinical systems: clinical information in surgical outpatient clinics, prescribing for hospital inpatients, equipment in theatres, and insertion of peripheral intravenous lines. The aim was to describe the nature, extent and variation in reliability of these four systems in a sample of UK hospitals, and to explore the reasons for poor reliability. Seven UK hospital organisations were involved; each system was studied in three of these. The authors took delivery of the systems' intended outputs to be a proxy for the reliability of the system as a whole. For example, for clinical information, 100% reliability was defined as all patients having an agreed list of clinical information available when needed during their appointment. Systems factors were explored using semi-structured interviews with key informants. Common themes across the systems were identified. Overall reliability was found to be between 81% and 87% for the systems studied, with significant variation between organisations for some systems: clinical information in outpatient clinics ranged from 73% to 96%; prescribing for hospital inpatients 82-88%; equipment availability in theatres 63-88%; and availability of equipment for insertion of peripheral intravenous lines 80-88%. One in five reliability failures were associated with perceived threats to patient safety. Common factors causing poor reliability included lack of feedback, lack of standardisation, and issues such as access to information out of working hours. Reported reliability was low for the four systems studied, with some common factors behind each. However, this hides significant variation between organisations for some processes, suggesting that some organisations have managed to create more reliable systems. Standardisation of processes would be expected to have significant benefit.


[Improvement of the feed value of straw by pelleting and sodium hydroxide addition. 1. Changes in the digestibility of rye and wheat straw].
Four series of pelleting experiments were conducted using straw from winter rye and winter wheat crops. Pelleting was done with and without grain addition. In each of the experimental series, 7 NaOH dosage levels were tested Further, 2 to 5% urea were added to the mixture to be pelleted. The 28 different pellet batsches and untreated straw were fed to sheep to study digestibility. Evaluation by difference trial revealed that straw pelleting without NaOH addition reduces the digestibility of organic matter by 4.7 units, on the average, whilst NaOH addition was found to increase digestibility depending on the dose applied. The following relationship was found between digestibility of straw dry matter (y) and NaOH dose in g/kg straw dry matter (x): y = 43.4 + 0.358x -0.00116x2. The grain proportion proved largely inert as far as the NaOH action is concerned. In one experimental series in which wheat straw without grain addition had been compacted at high pressing temperatures, an additional disintegration effect was observed irrespective of the NaOH dose applied. It increased digestibility by 8.0 units and is very likely to originate from the specific action of urea.


Genomic prediction of crossbred dairy cattle in Tanzania: A route to productivity gains in smallholder dairy systems.
Selection based on genomic predictions has become the method of choice for genetic improvement in dairy cattle. This offers huge opportunity for developing countries with little or no pedigree data, and preliminary studies have shown promising results. The African Dairy Genetic Gains (ADGG) project initiated a digital system of dairy performance data collection, accompanied by genotyping in Tanzania in 2016. Currently, ADGG has the largest body of dairy performance data generated in East Africa from a smallholder dairy system. This study examines the use of genomic best linear unbiased prediction (GBLUP) and single-step (ss)GBLUP for the estimation of genetic parameters and accuracy of genomic prediction for daily milk yield and body weight in Tanzania. The estimates of heritability for daily milk yield from GBLUP and ssGBLUP were essentially the same, at 0.12 ± 0.03. The heritability estimates for daily milk yield averaged over the whole lactation from random regression model (RRM) GBLUP or ssGBLUP were 0.22 and 0.24, respectively. The heritability of body weight from GBLUP was 0.24 ± 04 but was 0.22 ± 04 from the ssGBLUP analysis. Accuracy of genomic prediction for milk yield from a forward validation was 0.57 for GBLUP based on fixed regression model or 0.55 from an RRM. Corresponding estimates from ssGBLUP were 0.59 and 0.53, respectively. Accuracy for body weight, however, was much higher at 0.83 from GBLUP and 0.77 for ssGBLUP. The moderate to high levels of accuracy of genomic prediction (0.53-0.83) obtained for milk yield and body weight indicate that selection on the basis of genomic prediction is feasible in smallholder dairy systems and most probably the only initial possible pathway to implementing sustained genetic improvement programs in such systems.


Experience with prazosin in a clinical setting.
In a three-phase study that began in 1969, prazosin was shown to be especially suitable for use in treatment of hypertensive patients with gout, renal disease, or borderline diabetes, owing to the sparing of organ systems often harmed by other antihypertensive drugs.


Glucose Transporter Type I Deficiency (G1D) at 25 (1990-2015): Presumptions, Facts, and the Lives of Persons With This Rare Disease.
As is often the case for rare diseases, the number of published reviews and case reports of glucose transporter type I deficiency (G1D) approaches or exceeds that of original research. This can indicate medical interest, but also scientific stagnation. In assessing this state of affairs here, we focus not on what is peculiar or disparate about G1D, but on the assumptions that have reigned thus far undisputed, and critique them as a potential impediment to progress. To summarize the most common G1D phenotype, we trace the 25-year story of G1D in parallel with the natural history of one of two index patients, identified in 1990 by one of us (G.M.R.) and brought up to date by the other (J.M.P.) while later examining widely repeated but little-scrutinized statements. Among them are those that pertain to assumptions about brain fuels; energy failure; cerebrospinal glucose concentration; the purpose of ketogenic diet; the role of the defective blood-brain barrier; genotype-phenotype correlations; a bewildering array of phenotypes; ictogenesis, seizures, and the electroencephalograph; the use of mice to model the disorder; and what treatments may and may not be expected to accomplish. We reach the forgone conclusion that the proper study of mankind-and of one of its ailments (G1D) -is man itself (rather than mice, isolated cells, or extrapolated inferences) and propose a framework for rigorous investigation that we hope will lead to a better understanding and to better treatments for this and for rare disorders in general. These considerations, together with experience drawn from other disorders, lead, as a logical consequence, to the nullification of the view that therapeutic development (i.e., trials) for rare diseases could or should be accelerated without the most vigorous scientific scrutiny: trial and error constitute an inseparable couple, such that, at the present time, hastening the former is bound to precipitate the latter.


Characterization of premalignant neurogenic rat cells in vitro.
In long term culture of N-ethyl-N-nitrosourea (ENU) exposed fetal BD IX-rat brains, cells proliferate and form aggregates (nodules) in vitro, starting 2-3 months after the transplacental carcinogen injection in vivo. Cell nodules of cultures from 3-6 months after ENU exposure were investigated for the presence of organoid structures, signs of differentiation, and differentiation products. Organoid structures were absent as were signs of differentiation into more mature neuroglial cells since a relatively uniform immature cell population was typical for the nodules studied. Nuclear changes in form of nuclear envelope dilatation, margination and condensation of chromatin were present. The S-100 protein was generally expressed by the neuroglial cells in this premalignant phase; GFA and 14.3.2. protein were expressed to a variable degree. The cells showed enhanced proliferation. In conclusion there was a gradual change of differentiation accompanied by the acquisition of atypical nuclear structure in the premalignant phase studied.


Use of biological detection methods to assess dioxin-like compounds in sediments of Bohai Bay, China.
Bohai Bay, in the western region of northeastern China's Bohai Sea, receives water from large rivers containing various pollutants including dioxin-like compounds (DLCs). This study used the established zebrafish (Danio rerio) model, its known developmental toxicity endpoints and sensitive molecular analyses to evaluate sediments near and around an industrial effluent site in Bohai Bay. The primary objective was to assess the efficacy of rapid biological detection methods as an addition to chemical analyses. Embryos were exposed to various concentrations of sediment extracts as well as a 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) positive control. Exposure to sediment extract nearest the discharge site (P1) resulted in the most severe- and highest rates of change in embryos and larvae, suggesting that DLC contaminated sediment probably did not occur much beyond it. P1 extract resulted in concentration dependent increases in mortality and pericardial edema. Its highest concentration caused up-regulation of P-450 (CYP)-1A1(CYP1A) mRNA expression at 72 h post fertilization (hpf), an increase in its expression in gill arches as observed by whole mount in situ hybridization, and an increased signal in the Tg(cyp1a: mCherry) transgenic line. The pattern and magnitude of response was very similar to that of TCDD and supported the presence of DLCs in these sediment samples. Follow-up chemical analysis confirmed this presence and identified H7CDF, O8CDF and O8CDD as the main components in P1 extract. This study validates the use of biological assays as a rapid, sensitive, and cost-effective method to evaluate DLCs and their effects in sediment samples. Additionally, it provides support for the conclusion that DLCs have limited remobilization capacity in marine sediments.


[Characteristics of collagen metabolism in duodenal ulcer].
We studied the content of collagen metabolites in patients with duodenal ulcer (blood plasma, urea, and samples of the duodenal mucous tunic and mouth fluid). We also defined the role of an affected collagen metabolism in the formation and cicatrization of duodenal ulcer; finally, we ascertained that the nature of the detected changes in different biological substrate is unidirectional.


Accurate distortion estimation and optimal bandwidth allocation for scalable H.264 video transmission over MIMO systems.
In this paper, we propose an optimal strategy for the transmission of scalable video over packet-based multiple-input multiple-output (MIMO) systems. The scalable extension of H.264/AVC that provides a combined temporal, quality and spatial scalability is used. For given channel conditions, we develop a method for the estimation of the distortion of the received video and propose different error concealment schemes. We show the accuracy of our distortion estimation algorithm in comparison with simulated wireless video transmission with packet errors. In the proposed MIMO system, we employ orthogonal space-time block codes (O-STBC) that guarantee independent transmission of different symbols within the block code. In the proposed constrained bandwidth allocation framework, we use the estimated end-to-end decoder distortion to optimally select the application layer parameters, i.e., quantization parameter (QP) and group of pictures (GOP) size, and physical layer parameters, i.e., rate-compatible turbo (RCPT) code rate and symbol constellation. Results show the substantial performance gain by using different symbol constellations across the scalable layers as compared to a fixed constellation.


A global perspective of the genetic basis for carbonyl stress resistance.
The accumulation of protein adducts caused by carbonyl stress (CS) is a hallmark of cellular aging and other diseases, yet the detailed cellular effects of this universal phenomena are poorly understood. An understanding of the global effects of CS will provide insight into disease mechanisms and can guide the development of therapeutics and lifestyle changes to ameliorate their effects. To identify cellular functions important for the response to carbonyl stress, multiple genome-wide genetic screens were performed using two known inducers of CS. We found that different cellular functions were required for resistance to stress induced by methylglyoxal (MG) and glyoxal (GLY). Specifically, we demonstrate the importance of macromolecule catabolism processes for resistance to MG, confirming and extending known mechanisms of MG toxicity, including modification of DNA, RNA, and proteins. Combining our results with related studies that examined the effects of ROS allowed a comprehensive view of the diverse range of cellular functions affected by both oxidative and carbonyl stress. To understand how these diverse cellular functions interact, we performed a quantitative epistasis analysis by creating multimutant strains from those individual genes required for glyoxal resistance. This analysis allowed us to define novel glyoxal-dependent genetic interactions. In summary, using multiple genome-wide approaches provides an effective approach to dissect the poorly understood effects of glyoxal in vivo. These data, observations, and comprehensive dataset provide 1) a comprehensive view of carbonyl stress, 2) a resource for future studies in other cell types, and 3) a demonstration of how inexpensive cell-based assays can identify complex gene-environment toxicities.


Understanding the Effects of Stigma Messages: Danger Appraisal and Message Judgments.
Media coverage of health issues has been criticized for creating health stigmas. The model of stigma communication (MSC, Smith, 2007) provides insights into why this is so, but it has two problems: Some of its mediators have not been supported, and it does not do a good job of predicting the transmission of stigma messages (i.e., social transmission). We present a revised model of stigma message effects in which exposure to stigma messages leads to stigma beliefs and stigmatization as a result of a person-oriented danger appraisal. In addition, message judgments-shock value and common ground-are introduced as mediators of the relationship between danger appraisal and social transmission. Participants (N = 200) were randomly assigned to read a health story written either with or without the intrinsic features of stigma messages. The revised model of stigma-message effects was supported: Reading a health news story written with (vs. without) the intrinsic features of stigma messages resulted in greater danger appraisal, which directly predicted stigma-related outcomes and indirectly predicted social transmission through message judgments. Social transmission varied by message judgment: Shocking messages were shared in ways that facilitate diffusion, but common ground messages were shared with influential others, suggesting different means by which stigma as a collective norm may emerge from interactions among community members.


Cellular mechanism of action of metformin.
Metformin is a hypoglycemic drug effective in the treatment of non-insulin-dependent diabetes mellitus and increasingly used in Canada and Europe. Effects on intestinal glucose absorption, insulin secretion, and hepatic glucose production are insufficient to explain its hypoglycemic action, with most evidence suggesting that the major effect of the drug is on glucose utilization. In vivo and in vitro studies have demonstrated that metformin stimulates the insulin-induced component of glucose uptake into skeletal muscle and adipocytes in both diabetic individuals and animal models. This increase is more significant in diabetic than in nondiabetic animals, suggesting an enhanced action of the drug in the hyperglycemic state. The increase in glucose uptake is also reflected in an increase in the insulin-dependent portion of glucose oxidation. Potential sites of action of metformin are the insulin receptor and the glucose transporters. Although metformin increases insulin binding in various cell types, this effect is not universal and does not correlate with stimulation of glucose utilization. In contrast, direct effects of the drug on the glucose-transport system have been demonstrated. Metformin elevates the uptake of nonmetabolizable analogues of glucose in both nondiabetic rat adipocytes and diabetic mouse muscle. In the latter, the stimulatory effect of the drug is additive to that of insulin. In human and rat muscle cells in culture, metformin increases glucose-analogue transport independently of and additive to insulin, suggesting an insulin-dependent action. Most of these results suggest that the basis for the hypoglycemic effect of this biguanide is probably at the level of skeletal muscle by increasing glucose transport across the cell membrane.


Identification of genes regulating gene targeting by a high-throughput screening approach.
Homologous gene targeting (HGT) is a precise but inefficient process for genome engineering. Several methods for increasing its efficiency have been developed, including the use of rare cutting endonucleases. However, there is still room for improvement, as even nuclease-induced HGT may vary in efficiency as a function of the nuclease, target site, and cell type considered. We have developed a high-throughput screening assay for the identification of factors stimulating meganuclease-induced HGT. We used this assay to explore a collection of siRNAs targeting 19,121 human genes. At the end of secondary screening, we had identified 64 genes for which knockdown affected nuclease-induced HGT. Two of the strongest candidates were characterized further. We showed that siRNAs directed against the ATF7IP gene, encoding a protein involved in chromatin remodeling, stimulated HGT by a factor of three to eight, at various loci and in different cell types. This method thus led to the identification of a number of genes, the manipulation of which might increase rates of targeted recombination.


The influence of microplastics and halogenated contaminants in feed on toxicokinetics and gene expression in European seabass (Dicentrarchus labrax).
When microplastics pollute fish habitats, it may be ingested by fish, thereby contaminating fish with sorbed contaminants. The present study investigates how combinations of halogenated contaminants and microplastics associated with feed are able to alter toxicokinetics in European seabass and affect the fish. Microplastic particles (2%) were added to the feed either with sorbed contaminants or as a mixture of clean microplastics and chemical contaminants, and compared to feed containing contaminants without microplastics. For the contaminated microplastic diet, the accumulation of polychlorinated biphenyls (PCBs) and brominated flame retardants (BFRs) in fish was significantly higher, increasing up to 40 days of accumulation and then reversing to values comparable to the other diets at the end of accumulation. The significant gene expression results of liver (cyp1a, il1β, gstα) after 40 days of exposure indicate that microplastics might indeed exacerbate the toxic effects (liver metabolism, immune system, oxidative stress) of some chemical contaminants sorbed to microplastics. Seabass quickly metabolised BDE99 to BDE47 by debromination, probably mediated by deiodinase enzymes, and unlike other contaminants, this metabolism was unaffected by the presence of microplastics. For the other PCBs and BFRs, the elimination coefficients were significantly lower in fish fed the diet with contaminants sorbed to microplastic compared to the other diets. The results indicate that microplastics affects liver detoxification and lipid distribution, both of which affect the concentration of contaminants.


Reliability of the interprofessional collaborator assessment rubric (ICAR) in multi source feedback (MSF) with post-graduate medical residents.
Increased attention on collaboration and teamwork competency development in medical education has raised the need for valid and reliable approaches to the assessment of collaboration competencies in post-graduate medical education. The purpose of this study was to evaluate the reliability of a modified Interprofessional Collaborator Assessment Rubric (ICAR) in a multi-source feedback (MSF) process for assessing post-graduate medical residents' collaborator competencies. Post-graduate medical residents (n = 16) received ICAR assessments from three different rater groups (physicians, nurses and allied health professionals) over a four-week rotation. Internal consistency, inter-rater reliability, inter-group differences and relationship between rater characteristics and ICAR scores were analyzed using Cronbach's alpha, one-way and two-way repeated measures ANOVA, and logistic regression. Missing data decreased from 13.1% using daily assessments to 8.8% utilizing an MSF process, p = .032. High internal consistency measures were demonstrated for overall ICAR scores (α = .981) and individual assessment domains within the ICAR (α = .881 to .963). There were no significant differences between scores of physician, nurse, and allied health raters on collaborator competencies (F2,5 = 1.225, p = .297, η2 = .016). Rater gender was the only significant factor influencing scores with female raters scoring residents significantly lower than male raters (6.12 v. 6.82; F1,5 = 7.184, p = .008, η 2 = .045). The study findings suggest that the use of the modified ICAR in a MSF assessment process could be a feasible and reliable assessment approach to providing formative feedback to post-graduate medical residents on collaborator competencies.


[Serologic screening of infectious diseases in blood banks as an indicator of morbidity in the population].
Screening tests of 62,814 blood donations carried out between October 85 and October 87 in all five blood banks of Goiânia, Central Brazil, were analysed. The private institutions (3 blood banks) collected 80% of all donations and the remaining were collected by public blood banks. Seroprevalence of HIV, HBsAg, Chagas' disease and syphilis were compared with data obtained in the surveillance system and from previous surveys in an attempt to validate this source of health information. A seroprevalence of 0.07% for AIDS (one ELISA test) was calculated, which may suggest the presence of 1900 infected individuals, in the population of the State of Goiás as a whole. This figure seems reasonably close to the official data obtained by compulsory notification. For Chagas' disease, hepatitis B and syphilis seroprevalence of 3.3%, 1.3% and 4.1% were obtained, respectively. The potential usefulness and the limitations of screening in blood banks as a source of reliable morbidity indicator is discussed.


Neuroprotective and antinociceptive effects of rosemary (Rosmarinus officinalis L.) extract in rats with painful diabetic neuropathy.
Diabetes mellitus is associated with the development of neuronal tissue damage in different central and peripheral nervous system regions. A common complication of diabetes is painful diabetic peripheral neuropathy. We have explored the antihyperalgesic and neuroprotective properties of Rosmarinus officinalis L. extract (RE) in a rat model of streptozotocin (STZ)-induced diabetes. The nociceptive threshold and motor coordination of these diabetic rats was assessed using the tail-flick and rotarod treadmill tests, respectively. Activated caspase-3 and the Bax:Bcl-2 ratio, both biochemical indicators of apoptosis, were assessed in the dorsal half of the lumbar spinal cord tissue by western blotting. Treatment of the diabetic rats with RE improved hyperglycemia, hyperalgesia and motor deficit, suppressed caspase-3 activation and reduced the Bax:Bcl-2 ratio, suggesting that the RE has antihyperalgesic and neuroprotective effects in this rat model of STZ-induced diabetes. Cellular mechanisms underlying the observed effects may, at least partially, be related to the inhibition of neuronal apoptosis.


Association between gestational levels of toxic metals and essential elements and cerebral palsy in children.
Cerebral palsy (CP) is the most common motor disability in childhood, but its causes are only partly known. Early-life exposure to toxic metals and inadequate or excess amounts of essential elements can adversely affect brain and nervous system development. However, little is still known about these as perinatal risk factors for CP. This study aims to investigate the associations between second trimester maternal blood levels of toxic metals, essential elements, and mixtures thereof, with CP diagnoses in children. In a large, population-based prospective birth cohort (The Norwegian Mother, Father, and Child Cohort Study), children with CP diagnoses were identified through The Norwegian Patient Registry and Cerebral Palsy Registry of Norway. One hundred forty-four children with CP and 1,082 controls were included. The relationship between maternal blood concentrations of five toxic metals and six essential elements and CP diagnoses were investigated using mixture approaches: elastic net with stability selection to identify important metals/elements in the mixture in relation to CP; then logistic regressions of the selected metals/elements to estimate odds ratio (OR) of CP and two-way interactions among metals/elements and with child sex and maternal education. Finally, the joint effects of the mixtures on CP diagnoses were estimated using quantile-based g-computation analyses. The essential elements manganese and copper, as well as the toxic metal Hg, were the most important in relation to CP. Elevated maternal levels of copper (OR = 1.40) and manganese (OR = 1.20) were associated with increased risk of CP, while Hg levels were, counterintuitively, inversely related to CP. Metal/element interactions that were associated with CP were observed, and that sex and maternal education influenced the relationships between metals/elements and CP. In the joint mixture approach no significant association between the mixture of metals/elements and CP (OR = 1.00, 95% CI = [0.67, 1.50]) was identified. Using mixture approaches, elevated levels of copper and manganese measured in maternal blood during the second trimester could be related to increased risk of CP in children. The inverse associations between maternal Hg and CP could reflect Hg as a marker of maternal fish intake and thus nutrients beneficial for foetal brain development.


[Breast cancer grading by automated image processing].
Individual oncological therapy of carcinoma of the breast depends on information on the individual prognosis and malignancy. Image processing and analysis of the digital structure of the cellular nucleus adds new prognostic data to standard morphological and biochemical parameters and should be used for further individualisation of oncological therapy.


Morphing discrete diffraction in nonlinear Mathieu lattices.
Discrete optical gratings are essential components to customize structured light waves, determined by the band structure of the periodic potential. Beyond fabricating static devices, light-driven diffraction management requires nonlinear materials. Up to now, nonlinear self-action has been limited mainly to discrete spatial solitons. Discrete solitons, however, are restricted to the eigenstates of the photonic lattice. Here, we control light formation by nonlinear discrete diffraction, allowing for versatile output diffraction states. We observe morphing of diffraction structures for discrete Mathieu beams propagating nonlinearly in photosensitive media. The self-action of a zero-order Mathieu beam in a nonlinear medium shows characteristics similar to discrete diffraction in one-dimensional waveguide arrays. Mathieu beams of higher orders show discrete diffraction along curved paths, showing the fingerprint of respective two-dimensional photonic lattices.


An unexpected presentation of a traumatic wound on the lower lip: a case report.
Traumatic lip injuries present major challenges in terms of reconstructive options and the outcome of surgical management. The aetiology of lip injuries includes human bite as interpersonal violence. Bite wounds are always considered to be complex injuries contaminated with unique polymicrobial inoculum. A classification of facial bite injuries has been included and the surgical management of these lesions has also been discussed. We report a rare bite injury on the lower lip that resembled an ulcerative process. A 30-year-old African man presented with a severe tissue defect on his lower lip to a Dental and Oral Department in Tanzania. He explained that 12 days ago he had been involved in a fight and someone had bitten his lower lip. An orofacial examination confirmed a serious loss of lip tissue that resembled a chronic ulcerative process. Accurate assessment of the lesion was made by a thorough evaluation of some parameters such as size, depth, presence of granulation tissue, fibrin coverage, wound edges, exudates and/or necrosis. A surgical debridement under local anaesthesia was carried out. Afterwards a layered suture was performed. Eventually the healing was complete and satisfactory. A severe bite avulsive wound on the lower lip, despite the elapsed time before treatment, may have an excellent prognosis after a simple surgical procedure.


Association between cataract and cotinine-verified smoking status in 11 435 Korean adults using Korea National Health and Nutrition Examination Survey data from 2008 to 2016.
To investigate the association between cataract and cotinine-verified smoking status. Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, South Korea. Retrospective study. Participants were randomly selected using data collected by the Korea National Health and Nutrition Examination Survey from 2008 to 2016. Participants completed a questionnaire to self-report smoking status and a history of cataract, among other variables. To identify the relationship between cataract and smoking, a new variable was used to define smoking status, survey-cotinine-verified smoking status (SCS)-the combination of self-reported smoking status and cotinine-verified smoking status- and thus identify hidden smokers. In total, 11 435 participants were eligible for final analysis. The study comprised 4925 men and 6510 women; the mean age was 52.86 ± 16.83 years (median: 54 years). Of 2292 SCS smokers, 382 (16.7%) were nonsmokers according to their self-report. Notably, the ratio of the cotinine-verified to self-reported smoking rate of women was greater than that of men, 1.60 and 1.06, respectively. This indicated that female hidden smokers may affect the results of studies based on self-reported questionnaires. Multivariate logistic regression analysis showed that smoking was correlated with cataract (odds ratio [OR], 1.37 [95% CI, 1.07-1.76]; OR, 1.35 [CI, 1.12-1.64]; and OR, 1.36 [CI, 1.10-1.69]) for self-reported, cotinine-verified, and SCS, respectively. No statistically significant sex difference was found. Smoking was associated with cataract, but it did not vary by sex. Female hidden smoking must be considered when investigating the association between smoking and cataract based on self-reported questionnaires.


Recreational football for disease prevention and treatment in untrained men: a narrative review examining cardiovascular health, lipid profile, body composition, muscle strength and functional capacity.
Over the past 10 years, researchers have studied the effects of recreational football training as a health-promoting activity for participants across the lifespan. This has important public health implications as over 400 million people play football annually. Results from the first randomised controlled trial, published in the BJSM in January 2009, showed that football increased maximal oxygen uptake and muscle and bone mass, and lowered fat percentage and blood pressure, in untrained men, and since then more than 70 articles about football for health have been published, including publications in two supplements of the Scandinavian Journal of Medicine and Science in Sports in 2010 and 2014, prior to the FIFA World Cup tournaments in South Africa and Brazil. While studies of football training effects have also been performed in women and children, this article reviews the current evidence linking recreational football training with favourable effects in the prevention and treatment of disease in adult men.


Protective Effects of Ethanolic Extracts from Artichoke, an Edible Herbal Medicine, against Acute Alcohol-Induced Liver Injury in Mice.
Oxidative stress and inflammation are well-documented pathological factors in alcoholic liver disease (ALD). Artichoke (Cynara scolymus L.) is a healthy food and folk medicine with anti-oxidative and anti-inflammatory properties. This study aimed to evaluate the preventive effects of ethanolic extract from artichoke against acute alcohol-induced liver injury in mice. Male Institute of Cancer Research mice were treated with an ethanolic extract of artichoke (0.4, 0.8, and 1.6 g/kg body weight) by gavage once daily. Up to 40% alcohol (12 mL/kg body weight) was administered orally 1 h after artichoke treatment. All mice were fed for 10 consecutive days. Results showed that artichoke extract significantly prevented elevated levels of aspartate aminotransferase, alanine aminotransferase, triglyceride, total cholesterol, and malondialdehyde. Meanwhile, the decreased levels of superoxide dismutase and glutathione were elevated by artichoke administration. Histopathological examination showed that artichoke attenuated degeneration, inflammatory infiltration and necrosis of hepatocytes. Immunohistochemical analysis revealed that expression levels of toll-like receptor (TLR) 4 and nuclear factor-kappa B (NF-κB) in liver tissues were significantly suppressed by artichoke treatment. Results obtained demonstrated that artichoke extract exhibited significant preventive protective effect against acute alcohol-induced liver injury. This finding is mainly attributed to its ability to attenuate oxidative stress and suppress the TLR4/NF-κB inflammatory pathway. To the best of our knowledge, the underlying mechanisms of artichoke on acute ALD have been rarely reported.


Financial dashboard reporting for the hospital industry.
Most senior executives and board members experience information overload in their decision making roles. They simply receive an excessive amount of unrelated data that is not benchmarked to standards that enable them to make effective decisions. This is an unfortunate situation given the information technology and the availability of public data that exists today. Many firms in a variety of industry sectors have combined the concept of "balanced scorecards" with "dashboard" reporting to revamp their senior level executive reporting systems. A sample dashboard reporting system for a hospital is outlined in this paper.


Pulmonary inflammatory cell response to sustained endotoxin administration.
We have developed a model of human sepsis in sheep. Twenty-four hours after continuous infusion of Escherichia coli endotoxin (lipopolysaccharide) (10 ng.kg-1.min-1) was begun, pulmonary transvascular fluid flux was almost five times the baseline values, cardiac output was nearly doubled, and mean arterial pressure was reduced by approximately 20 mmHg. At this time, the animals were killed and their lungs were fixed by endotracheal installation of 2.5% glutaraldehyde at 25 cmH2O pressure. Morphometry was performed by point counting, and data were expressed as relative volume density. Pulmonary edema and congestion were observed in sheep receiving lipopolysaccharide, whereas sham controls appeared normal. There was an increase in interstitial volume density. There was a significant increase (P < 0.01) in volume density of the pulmonary intravasculature (180%), interstitial macrophages (270%), and mast cells (240%). The volume densities of intravascular and interstitial polymorphonuclear neutrophils also showed a small insignificant increase.


Assessment of social and economic influences on blood pressure of adolescents in public and private schools: an epidemiological study.
The high prevalence of hypertension in high school students in Sorocaba, São Paulo, Brazil, has already been described. In this study, within a new sample of high school students from public and private schools, we evaluated if socioeconomic and lifestyle influence on blood pressure values. This is an epidemiological study, which is part of the activities of a community-based work conducted by medical students. They give speeches to high school students aiming at stimulating a healthy lifestyle and primary prevention of hypertension. In a random sample of 410 students in junior high school (209 from public schools and 201 from private schools), we determined the weight, height, and blood pressure, furthermore, a questionnaire identifying epidemiological and socioeconomic status was applied. No statistical differences were found among students from public and private schools regarding the distribution of gender, body mass index (BMI), systolic and diastolic blood pressure, prevalence of hypertension (16.3%), percentage of smokers (5.9%), regular physical activity, and family history of hypertension. In public schools, there is a higher percentage of African descendents students and a higher percentage of students who also work due to low family income. Men from public and private schools have higher prevalence of hypertension, and their mean blood pressure is higher than in women. BMI has a positive correlation with systolic and diastolic blood pressure. Hypertension and other cardiovascular risk factors have an early beginning and require educational interventions for primary prevention. Socioeconomic factors do not affect blood pressure in adolescence.


Major gynecologic and obstetric surgery in Jehovah's Witnesses.
A retrospective study of 165 Jehovah's Witnesses and 164 Jehovah's Witnesses and 164 control patients compared the morbidity and mortality associated with major obstetric and gynecologic surgery in the 2 groups. There were no deaths and few complications in either group. There were few differences in preoperative and postoperative hemoglobin values. Medicolegal implications of performing major surgery without blood transfusions are discussed. The study adds evidence that major operative procedures can be carried out on Jehovah's Witness patients without blood transfusions or blood products.


Effectiveness of Trigger Point Manual Treatment on the Frequency, Intensity, and Duration of Attacks in Primary Headaches: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
A variety of interventions has been proposed for symptomatology relief in primary headaches. Among these, manual trigger points (TrPs) treatment gains popularity, but its effects have not been investigated yet. The aim was to establish the effectiveness of manual TrP compared to minimal active or no active interventions in terms of frequency, intensity, and duration of attacks in adult people with primary headaches. We searched MEDLINE, COCHRANE, Web Of Science, and PEDro databases up to November 2017 for randomized controlled trials (RCTs). Two independent reviewers appraised the risk-of-bias (RoB) and the grading of recommendations, assessment, development, and evaluation (GRADE) to evaluate the overall quality of evidence. Seven RCTs that compared manual treatment vs minimal active intervention were included: 5 focused on tension-type headache (TTH) and 2 on Migraine (MH); 3 out of 7 RCTs had high RoB. Combined TTH and MH results show statistically significant reduction for all outcomes after treatment compared to controls, but the level of evidence was very low. Subgroup analysis showed a statistically significant reduction in attack frequency (no. of attacks per month) after treatment in TTH (MD -3.50; 95% CI from -4.91 to -2.09; 4 RCTs) and in MH (MD -1.92; 95% CI from -3.03 to -0.80; 2 RCTs). Pain intensity (0-100 scale) was reduced in TTH (MD -12.83; 95% CI from -19.49 to -6.17; 4 RCTs) and in MH (MD -13.60; 95% CI from -19.54 to -7.66; 2RCTs). Duration of attacks (hours) was reduced in TTH (MD -0.51; 95% CI from -0.97 to -0.04; 2 RCTs) and in MH (MD -10.68; 95% CI from -14.41 to -6.95; 1 RCT). Manual TrPs treatment of head and neck muscles may reduce frequency, intensity, and duration of attacks in TTH and MH, but the quality of evidence according to GRADE approach was very low for the presence of few studies, high RoB, and imprecision of results.


EMG-FRNet: A feature reconstruction network for EMG irrelevant gesture recognition.
With the development of deep learning technology, gesture recognition based on surface electromyography (EMG) signals has shown broad application prospects in various human-computer interaction fields. Most current gesture recognition technologies can achieve high recognition accuracy on a wide range of gesture actions. However, in practical applications, gesture recognition based on surface EMG signals is susceptible to interference from irrelevant gesture movements, which affects the accuracy and security of the system. Therefore, it is crucial to design an irrelevant gesture recognition method. This paper introduces the GANomaly network from the field of image anomaly detection into surface EMG-based irrelevant gesture recognition. The network has a small feature reconstruction error for target samples and a large feature reconstruction error for irrelevant samples. By comparing the relationship between the feature reconstruction error and the predefined threshold, we can determine whether the input samples are from the target category or the irrelevant category. In order to improve the performance of EMG irrelevant gesture recognition, this paper proposes a feature reconstruction network named EMG-FRNet for EMG irrelevant gesture recognition. This network is based on GANomaly and incorporates structures such as channel cropping (CC), cross-layer encoding-decoding feature fusion (CLEDFF), and SE channel attention (SE). In this paper, Ninapro DB1, Ninapro DB5 and self-collected datasets were used to verify the performance of the proposed model. The Area Under the receiver operating characteristic Curve (AUC) values of EMG-FRNet on the above three datasets were 0.940, 0.926 and 0.962, respectively. Experimental results demonstrate that the proposed model achieves the highest accuracy among related research.


[Primary leiomyosarcoma of the omentum].
The clinical and histological findings of a patient with a primary omental leiomyosarcoma are described. A 29 years old female patient presented with a 11 month history of constipation, progressive abdominal swelling and weight gain over the last 4 months. On physical examination a large abdominal tumor was found. An ultrasonographic evaluation disclosed a giant mass with a mixed content, of approximately 40 x 17 cm size. Two days latter a celiotomy was done, finding the tumor mass depending of the great omentum, with high vascularity and no evidence of metastasis. A complete resection was performed. The histopathologic report was of primary omental leiomyosarcoma. This tumor is very rare and the case presented is possibly the sixth in the indexed world literature.


Extracellular histones play an inflammatory role in acid aspiration-induced acute respiratory distress syndrome.
Systemic inflammation is a key feature in acid aspiration-induced acute respiratory distress syndrome (ARDS), but the factors that trigger inflammation are unclear. The authors hypothesize that extracellular histones, a newly identified inflammatory mediator, play important roles in the pathogenesis of ARDS. The authors used a hydrochloric acid aspiration-induced ARDS model to investigate whether extracellular histones are pathogenic and whether targeting histones are protective. Exogenous histones and antihistone antibody were administered to mice. Heparin can bind to histones, so the authors studied whether heparin could protect from ARDS using cell and mouse models. Furthermore, the authors analyzed whether extracellular histones are clinically involved in ARDS patients caused by gastric aspiration. Extracellular histones in bronchoalveolar lavage fluid of acid-treated mice were significantly higher (1.832 ± 0.698) at 3 h after injury than in sham-treated group (0.63 ± 0.153; P = 0.0252, n = 5 per group). Elevated histones may originate from damaged lung cells and neutrophil infiltration. Exogenous histones aggravated lung injury, whereas antihistone antibody markedly attenuated the intensity of ARDS. Notably, heparin provided a similar protective effect against ARDS. Analysis of plasma from ARDS patients (n = 21) showed elevated histones were significantly correlated with the degree of ARDS and were higher in nonsurvivors (2.723 ± 0.2933, n = 7) than in survivors (1.725 ± 0.1787, P = 0.006, n = 14). Extracellular histones may play a contributory role toward ARDS by promoting tissue damage and systemic inflammation and may become a novel marker reflecting disease activity. Targeting histones by neutralizing antibody or heparin shows potent protective effects, suggesting a potentially therapeutic strategy.


Prognostic value of patient-reported quality of life for survival in oesophagogastric cancer: analysis from the population-based POCOP study.
Accumulating evidence of trials demonstrates that patient-reported health-related quality of life (HRQoL) at diagnosis is prognostic for overall survival (OS) in oesophagogastric cancer. However, real-world data are lacking. Moreover, differences in disease stages and tumour-specific symptoms are usually not taken into consideration. The aim of this population-based study was to assess the prognostic value of HRQoL, including tumour-specific scales, on OS in patients with potentially curable and advanced oesophagogastric cancer. Data were derived from the Netherlands Cancer Registry and the patient reported outcome registry (POCOP). Patients included in POCOP between 2016 and 2018 were stratified for potentially curable (cT1-4aNallM0) or advanced (cT4b or cM1) disease. HRQoL was measured with the EORTC QLQ-C30 and the tumour-specific OG25 module. Cox proportional hazards models assessed the impact of HRQoL, sociodemographic and clinical factors (including treatment) on OS. In total, 924 patients were included. Median OS was 38.9 months in potentially curable patients (n = 795) and 10.6 months in patients with advanced disease (n = 129). Global Health Status was independently associated with OS in potentially curable patients (HR 0.89, 99%CI 0.82-0.97), together with several other HRQoL items: appetite loss, dysphagia, eating restrictions, odynophagia, and body image. In advanced disease, the Summary Score was the strongest independent prognostic factor (HR 0.75, 99%CI 0.59-0.94), followed by fatigue, pain, insomnia and role functioning. In a real-world setting, HRQoL was prognostic for OS in patients with potentially curable and advanced oesophagogastric cancer. Several HRQoL domains, including the Summary Score and several OG25 items, could be used to develop or update prognostic models.


Compensatory Neural Tract from Contralesional Fornical Body to Ipsilesional Medial Temporal Lobe in a Patient with Mild Traumatic Brain Injury: A Case Report.
The authors attempted to demonstrate the compensatory process for an injured fornical crus after mild traumatic brain injury, using follow-up diffusion tensor tractography. A 50-yr-old female patient had a mild traumatic brain injury resulting from a collision that occurred while driving a sedan that was hit from the side. The patient complained of memory impairment since the onset of head trauma and underwent neuropsychologic evaluation at 2 mos after onset with global memory: 77 (6%ile) on the Memory Assessment Scale. She underwent rehabilitation, including cognitive therapy and cholinergic drugs until 12 mos after onset. At that time, she showed improvement of memory impairment with global memory: 90 (25%ile) on the Memory Assessment Scale. On 2-mo diffusion tensor tractography, a discontinuation was observed in the left fornical crus. By contrast, on 12-mo diffusion tensor tractography, the left discontinued fornical crus was shortened; instead, a neural tract from the right fornical body extended to the left medial temporal lobe via the splenium of the corpus callosum and the left fornical column was elongated to the left medial temporal lobe. The authors report on a patient who showed a compensatory neural tract from the contralesional fornical body to the ipsilesional medial temporal lobe via the corpus callosum after mild traumatic brain injury.


The modular curriculum of medicine at the Charité Berlin - a project report based on an across-semester student evaluation.
Aim: The introduction of a reform clause into the German licensing laws for medical doctors has enabled German faculties to pilot alternative designs for medical degree programmes. The aim of this project report is to outline the curricular features of the modular curriculum of medicine (MCM) at the Charité and to assess the results of its implementation based on a student evaluation across semesters. Project outline: The MCM was planned and implemented in a competency- and outcome-based manner from 2010-2016 in a faculty-wide process. The curriculum is characterised by a modular structure, longitudinal teaching formats and the integration of basic and clinical science. In the winter semester 2017, evaluations by students in semesters 1-10 were carried out. The results were analysed descriptively, and the coverage of overarching learning outcomes was compared to the results of a survey carried out amongst students on the traditional regular curriculum of medicine track in 2016. Results: A total of 1,047 students participated in the across-semester evaluation (return rate 35%). A high percentage of the respondents positively rated the achieved curricular integration and longitudinal teaching formats. The majority of the respondents agreed with the relevance of the overarching learning outcomes. Students' evaluations of the coverage of learning outcomes showed a differentiated picture for the MCM. Compared to the regular curriculum track, the coverage in the MCM programme showed substantial improvements in all aspects. Students found themselves to be better prepared for the M2 state examination and the practical year. The students' overall satisfaction with their decisions to study in the MCM was high. Conclusions: The results of the student evaluation show that a significant improvement in medical education has been achieved at the Charité with the new integrated, outcome-oriented design and the implementation of the MCM. At the same time, ongoing weaknesses have been revealed that serve as a basis for the continued development of the curriculum. This report aims to contribute to the discussion of the future of undergraduate medical education in Germany.


Serotonergic drugs for depression and beyond.
The current generation of antidepressant drugs acts predominantly by targeting the serotonin transporter (SERT). The original trend to do this selectively (e.g., with SSRIs or selective serotonin reuptake inhibitors) has given way to combining various additional pharmacologic mechanisms with SERT inhibition, including dual actions by single drugs (e.g., SNRIs or serotonin norepinephrine reuptake inhibitors), or by augmenting SSRIs with a second drug of a different mechanism (e.g., bupropion with dopamine and norepinephrine reuptake inhibition; trazodone with 5HT2A antagonism; mirtazapine with 5HT2A/5HT2C/5HT3/alpha2 antagonism; buspirone or some atypical antipsychotics with 5HT1A partial agonism; other atypical antipsychotics with 5HT2C/5HT7 antagonism and other mechanisms). Novel drugs in development include those that combine multiple simultaneous pharmacologic mechanisms in addition to SERT inhibition within the same molecule, such as vilazodone (combining 5HT1A partial agonism with SERT inhibition), triple reuptake inhibitors (combining norepinephrine and dopamine reuptake inhibition with SERT inhibition), and vortioxetine, a multimodal antidepressant combining actions at the G protein receptor mode (5HT1A and 5HT1B partial agonism and 5HT7 antagonism), at the ion channel mode (5HT3 antagonism) as well as the neurotransmitter transporter mode (SERT inhibition). These various strategies that build upon SERT inhibition provide promise for novel therapeutic approaches to depression, including the possibility of targeting residual symptoms not well treated by SERT inhibition alone, and reducing side effects, such as sexual dysfunction.


Divergent four-point dynamic density correlation function of a glassy suspension.
We use a recently derived diagrammatic formulation of the dynamics of interacting Brownian particles [G. Szamel, J. Chem. Phys. 127, 084515 (2007)10.1063/1.2759487] to study a four-point dynamic density correlation function. We resum a class of diagrams which separate into two disconnected components upon cutting a single propagator. The resulting formula for the four-point correlation function can be expressed in terms of three-point functions closely related to the three-point susceptibility introduced by Biroli et al. [Phys. Rev. Lett. 97, 195701 (2006)10.1103/PhysRevLett.97.195701] and the standard two-point correlation function. The four-point function has a structure very similar to that proposed by Berthier and collaborators [Science 310, 1797 (2005)10.1126/science.1120714; J. Chem. Phys. 126, 184503 (2007)10.1063/1.2721554]. It exhibits a small wave vector divergence at the mode-coupling transition.


[New data on thymomegaly as a syndrome of congenital (primary) immunodeficiency].
Basing on a combined clinicomorphological investigation of the thymicolymphatic and neuroendocrine systems including measurements of blood thymic hormones and their levels in thymic tissue it is shown that congenital thymomegaly can be considered a dysfunction of the hypothalamo-hypophysial system. The dysfunction manifests with polyglandular endocrinopathy and congenital immunodeficiency related to the group of thymus-dependent immunodeficiencies. Thymomegaly is often coupled with congenital malformations.


Cost identification of abdominal aortic aneurysm imaging by using time and motion analyses.
To compare the costs of performing helical computed tomographic (CT) angiography with three-dimensional rendering versus intraarterial digital subtraction angiography (DSA) for preoperative imaging of abdominal aortic aneurysms (AAAs). A single observer determined the variable direct costs of performing nine intraarterial DSA and 10 CT angiographic examinations in age- and general health-matched patients with AAA by using time and motion analyses. All personnel directly involved in the cases were tracked, and the involvement times were recorded to the nearest minute. All material items used during the procedures were recorded. The cost of labor was determined from personnel reimbursement data, and the cost of materials, from vendor pricing. The variable direct costs of laboratory tests and using the ambulatory treatment unit for postprocedural monitoring, as well as all fixed direct costs, were assessed from hospital accounting records. The total costs were determined for each procedure and compared by using the Student t test and calculating the CIs. The mean total direct cost of intraarterial DSA (+/- SD) was $1,052 +/- 71, and that of CT angiography was $300 +/- 30, which are significantly different (P < 4.1 x 10(-11)). With 95% confidence, intraarterial DSA cost 3.2-3.7 times more than CT angiography for the assessment of AAA. Assuming equal diagnostic utility and procedure-related morbidity, institutions may have substantial cost savings whenever CT angiography can replace intraarterial DSA for imaging AAAs.


Association of a common variant of the CASP8 gene with reduced risk of breast cancer.
Apoptosis, or programmed cell death, is perturbed in many cancers. We tested the hypothesis that coding polymorphisms of the death receptor 4 (DR4), caspase-8 (CASP8), and caspase-10 (CASP10) genes might act as low-penetrance breast cancer genes. Single-nucleotide polymorphisms (SNPs) of these genes were genotyped in a series of 999 breast cancer case patients and 996 control subjects from Sheffield, U.K., and in a second, independent U.K. population of 2192 case patients and 2262 control subjects from East Anglia. In the Sheffield study, the rare H allele of CASP8, D302H, was associated with a reduced risk of breast cancer in a dose-dependent manner (P(trend) = .007). Furthermore, the CASP8 D302H association, but not that of the other CASP8 SNPs examined (T21914C, G50121A, and G50358A), was replicated in the East Anglian study. The combined adjusted odds ratios for breast cancer were 0.83 (95% confidence interval [CI] = 0.74 to 0.94) for the DH heterozygote and 0.58 (95% CI = 0.39 to 0.88) for the HH homozygote (P(trend) = .0002, adjusted for study). The reproducible, dose-dependent association of CASP8 D302H with breast cancer indicates the potential importance of inherited variation in the apoptosis pathway in breast cancer susceptibility.


Quality of caesarean delivery services and documentation in first-line referral facilities in Afghanistan: a chart review.
Increasing appropriate use and documentation of caesarean section (CS) has the potential to decrease maternal and perinatal mortality in settings with low CS rates. We analyzed data collected as part of a comprehensive needs assessment of emergency obstetric and newborn care (EmONC) facilities in Afghanistan to gain a greater understanding of the clinical indications, timeliness, and outcomes of CS deliveries. Records were reviewed at 78 government health facilities expected to function as EmONC providers that were located in secure areas of the country. Information was collected on the three most recent CS deliveries in the preceding 12 months at facilities with at least one CS delivery in the preceding three months. After excluding 16 facilities with no recent CS deliveries, the sample includes 173 CS deliveries at 62 facilities. No CS deliveries were performed in the previous three months at 21% of facilities surveyed; all of these were lower-level facilities. Most CS deliveries (88%) were classified as emergencies, and only 12% were referrals from another facility. General anesthesia was used in 62% of cases, and spinal or epidural anesthesia in 34%. Only 28% of cases were managed with a partograph. Surgery began less than one hour after the decision for a CS delivery in just 30% of emergency cases. Among the 173 cases, 27 maternal deaths, 28 stillbirths, and 3 early neonatal deaths were documented. In cases of maternal and fetal death, the most common indications for CS delivery were placenta praevia or abruption and malpresentation. In 62% of maternal deaths, the fetus was stillborn or died shortly after birth. In 48% of stillbirths, the fetus had a normal heart rate at the last check. Information on partograph use was missing in 38% of cases, information on parity missing in 23% of cases and indications for cesareans missing in 9%. Timely referral within and to EmONC facilities would decrease the proportion of CS deliveries that develop to emergency status. While the substantial mortality associated with CS in Afghanistan may be partly due to women coming late for obstetric care, efforts to increase the availability and utilization of CS must also focus on improving the quality of care to reduce mortality. Key goals should be encouraging use of partographs and improving decision-making and documentation around CS deliveries.


Weighted Walking Influences Lower Extremity Coordination in Children on the Autism Spectrum.
There is sparse quantitative research regarding gait coordination patterns of children on the autism spectrum, though previous studies, relying only upon observational data, have alluded to characteristically poor movement coordination. This study compared walking with a weighted vest, a backpack carriage, and an unloaded walking condition on lower extremity coordination among 10 male children (aged 8-17 years) on the autism spectrum. All participants completed 15 gait trials in the following three conditions: (a) unloaded, (b) wearing a backpack weighted with 15% body mass, and (c) wearing a vest weighted with 15% body mass. We used continuous relative phase analysis to quantify lower extremity coordination and analyzed data through both group and single-subject comparisons. We used the Model Statistic to test for statistical significance at each of the normalized data points for each segment couple (thigh-leg, leg-foot, and thigh-foot). The first 10 and last 10 stride blocks were tested for possible accommodation strategies. Group comparisons revealed no coordination changes among the three conditions (likely due to insufficient statistical power), while single-subject comparisons exposed significant decreased variability in gait coordination patterns ( p < .05) in both loaded conditions, relative to the unloaded condition. These participants exhibited variable coordination patterns during the unloaded gait. When walking with loads, coordination pattern variability of the lower extremities was decreased. This finding suggests that walking while carrying or wearing heavy objects may reduce the number of potential motor pattern choices and thus decrease the overall variability of lower extremity movement patterns. Additional research with a larger and more diverse participant sample is required to confirm this conclusion.


The microbiology of stockfish during the drying process.
Stockfish is made by drying species of fish in the open air to a final water content of 17-18% (w/w). By this treatment the fish acquires a very characteristic flavour. A study was made of the microbiology of blue ling (Molva dypterygia dypterygia) during this process. Aerobic plate counts at 22 degrees C in the flesh of the fish reached a maximum of 4.1 x 10(7)/g dry weight, after drying for 30 days. Analyses of the aerobic/facultatively anaerobic bacterial flora in the flesh showed initially a dominance of Moraxella and Acinetobacter-like spp. As the drying progressed a Gram positive, catalase negative flora appeared, increasing its proportion to 77% of the bacterial content of the fish. Representative strains of these bacteria were identified as Lactobacillus plantarum.


Urothelial cancer and some industry-related chemicals: an evaluation of the epidemiologic literature.
In a previous cohort study by our group, certain industry-related chemicals were judged as warranting further attention as possible urothelial carcinogens. In this paper, the epidemiologic literature of cancer of the lower urinary tract is evaluated for these substances. We would like to add combustion gases/soot from coal to the substances considered as increasing the risk of urothelial cancer. It is, however, uncertain whether this risk is due to contaminants of aromatic amines in tar volatiles or whether it depends on other agents, such as nitroarenes or polycyclic aromatic hydrocarbons. Furthermore, we find some support for the hypothesis that exposure to chlorinated aliphatic hydrocarbons increases the risk of urothelial cancer. For creosote, cutting fluids and cutting oils, hair dyes, and polychlorinated biphenyls, data are scarce. Available data do not support the hypothesis that asbestos is associated with urothelial cancer. "Publication bias," such that only limited information was available, was judged to be a potential problem in the review for many, but not all, of the substances investigated.


6-Gingerol, an active constituent of ginger, attenuates lipopolysaccharide-induced oxidation, inflammation, cognitive deficits, neuroplasticity, and amyloidogenesis in rat.
This study examined the protective effect of 6-Gingerol (6G) against lipopolysaccharide (LPS)-induced cognitive impairments, oxidative stress, neuroplasticity, amyloidogenesis, and inflammation. Male rats were allocated into six groups in this manner; Group I placed on normal saline only. Group II was treated for 7 days with LPS alone intraperitoneally at 250 µg/kg body weight (bw). Group III received 6G alone at 50 mg/kg bw orally for 14 days. Groups IV and V received 6G at 20 and 50 mg/kg bw for 7 days, respectively, and LPS for another 7 days to induce neurotoxicity. Group VI received 5 mg/kg bw of donepezil for 7 days and LPS for 7 days. Pretreatment with 20 and 50 mg/kg bw of 6G protected against LPS-mediated learning and memory function, and also locomotor and motor deficits. Besides, 20 and 50 mg/kg bw 6G mitigated LPS-induced alteration in markers of oxidative stress. Furthermore, induction of amyloidogenesis associated with disruption of histoarchitecture and high expression of interleukin 1β, inducible nitric oxide synthase, amyloid precursor protein (APP), β-secretase 1, and brain-derived neurotrophic factor by LPS was mitigated by the two doses of 6G in the rat hippocampus and cerebral cortex region of the brain. 6G pretreatment at the two doses mitigated LPS-mediated histopathological changes in the hippocampus and cerebral cortex of rats. Overall, our results demonstrate that the protective effect of 6G is mediated through the reversal of neurobehavioral deficit, oxidative stress, inflammation, and amyloidogenesis, thus making 6G a possible chemoprophylactic agent against brain injury as a result of LPS exposure. PRACTICAL APPLICATIONS: In the search for a holistic prevention of inflammation-associated neurodegeneration, nutraceuticals are becoming prominent. Hence, this study presents 6G, an active constituent of ginger, as a chemoprotective, antioxidant, and anti-inflammatory agent, which is able to ameliorate cognitive impairments, oxidative stress, neuroplasticity, amyloidogenesis, and inflammation in LPS-induced rat model of neuroinflammation.


Current Progress in Electrotransfection as a Nonviral Method for Gene Delivery.
Electrotransfection (ET) is a nonviral method for delivery of various types of molecules into cells both in vitro and in vivo. Close to 90 clinical trials that involve the use of ET have been performed, and approximately half of them are related to cancer treatment. Particularly, ET is an attractive technique for cancer immunogene therapy because treatment of cells with electric pulses alone can induce immune responses to solid tumors, and the responses can be further enhanced by ET of plasmid DNA (pDNA) encoding therapeutic genes. Compared to other gene delivery methods, ET has several unique advantages. It is relatively inexpensive, flexible, and safe in clinical applications, and introduces only naked pDNA into cells without the use of additional chemicals or viruses. However, the efficiency of ET is still low, partly because biological mechanisms of ET in cells remain elusive. In previous studies, it was believed that pDNA entered the cells through transient pores created by electric pulses. As a result, the technique is commonly referred to as electroporation. However, recent discoveries have suggested that endocytosis plays an important role in cellular uptake and intracellular transport of electrotransfected pDNA. This review will discuss current progresses in the study of biological mechanisms underlying ET and future directions of research in this area. Understanding the mechanisms of pDNA transport in cells is critical for the development of new strategies for improving the efficiency of gene delivery in tumors.


TaS3 Nanofibers: Layered Trichalcogenide for High-Performance Electronic and Sensing Devices.
Layered materials, like transition metal dichalcogenides, exhibit broad spectra with outstanding properties with huge application potential, whereas another group of related materials, layered transition metal trichalcogenides, remains unexplored. Here, we show the broad application potential of this interesting structural type of layered tantalum trisulfide prepared in a form of nanofibers. This material shows tailorable attractive electronic properties dependent on the tensile strain applied to it. Structure of this so-called orthorhombic phase of TaS3 grown in a form of long nanofibers has been solved and refined. Taking advantage of these capabilities, we demonstrate a highly specific impedimetric NO gas sensor based on TaS3 nanofibers as well as construction of photodetectors with excellent responsivity and field-effect transistors. Various flexible substrates were used for the construction of a NO gas sensor. Such a device exhibits a low limit of detection of 0.48 ppb, well under the allowed value set by environmental agencies for NOx (50 ppb). Moreover, this NO gas sensor also showed excellent selectivity in the presence of common interferences formed during fuel combustion. TaS3 nanofibers produced in large scale exhibited excellent broad application potential for various types of devices covering nanoelectronic, optoelectronic, and gas-sensing applications.


Selective influence of menstrual cycle on perception of stimuli with reproductive significance.
Sixteen healthy women (20-32 years) not taking oral contraceptives were tested at three phases of their menstrual cycles (menses, preovulatory phase, and midluteal phase). Another 16 women taking oral contraceptives served as age-matched controls, and were tested during menses and during phases corresponding to the preovulatory and midluteal phase. On each test occasion, perception was assessed of visual stimuli belonging to three categories: sex (nude men), babies, and stimuli related to body care. Also, meaningless syllables were given. Stimuli were presented by a tachistoscope. Presentation of each stimulus was repeated until the subject signaled recognition. Trials to recognition and correctness of the recognition response were recorded. In spontaneously cycling women effects of the phase of the menstrual cycle depended on the stimulus meaning: During the preovulatory phase, there was an increase in the number of correctly recognized sex stimuli (p < 0.05) and of stimuli falsely recognized as sex stimuli (p < 0.05). The number of stimuli falsely recognized as body care was reduced during this phase (p < 0.05). Moreover, during the luteal phase, the number of trials to recognition of baby stimuli was diminished (p < 0.01). In women taking contraceptives, no stimulus specific changes occurred, but correct recognition was generally improved during the luteal phase. Rather than supporting a general influence of the normal menstrual cycle on perceptual functions, the present results demonstrate that the effects of the menstrual cycle depend on the meaning of the stimulus with the perception of sexual stimuli, but not of stimuli related to maternal nurture, being improved during the preovulatory phase.


RESPIRATORY EFFECTS UPON THE VISUAL THRESHOLD.
Measurements are reported of the effects of respiratory stresses upon the absolute threshold of peripheral (rod) vision. Since subjects were kept wholly dark adapted and the photochemical system of the rods therefore stationary, the changes recorded may be assumed to have originated more centrally. To this degree the measurements provide a quantitative index of central nervous imbalance. Breathing room air or 32 to 36 per cent oxygen at about double the normal rate causes the visual threshold to fall to approximately half the normal value within 5 to 10 minutes. This change is due primarily to alkalosis induced by the hyperventilation, and can be abolished or reversed by adding carbon dioxide to the inspired mixtures. Normal or rapid breathing of 2 per cent carbon dioxide causes no change in threshold; with 5 per cent carbon dioxide the threshold is approximately doubled. Breathing 10 per cent oxygen at the normal rate also approximately doubles the threshold. This effect is compensated in part by rapid breathing. When 10 per cent oxygen is breathed at twice the normal rate the threshold usually falls at first, then slowly rises to supernormal levels. Due primarily to variations in their breathing patterns subjects yield characteristically different responses on sudden exposure to low oxygen tensions with breathing uncontrolled. The threshold may either rise or fall; and on release from anoxia it may rise, or fall to normal or subnormal levels. The threshold adjusts to anoxia rapidly; exposures lasting 5 to 6 hours do not produce greater or more persistent changes than those of much shorter duration.


Outcomes of Endoscopic Therapy for Luminal Strictures in Crohn's Disease.
We sought to describe the outcomes of endoscopic therapy of luminal strictures in patients with Crohn's disease (CD) at a large tertiary referral center. All patients who had undergone endoscopic dilation of CD strictures between January 1, 1990 and November 30, 2013 were identified. Demographics, disease characteristics including medication use and history of surgeries, details of endoscopic procedures, and long-term outcomes were analyzed. A successful procedure was defined as ability of the endoscope to pass through the stricture after dilation or effacement of the dilating balloon under fluoroscopy. Kaplan-Meier and Cox proportional hazards analysis were used. For this study 286 index procedures for CD-related stricture dilation were performed in 273 patients (53.8% women) with median age of 45.9 years (range, 14.9-92.2). The most common stricture locations were ileocolonic anastomosis (36.4%) and colon (13.9%). One hundred fourteen (41.8%) patients had a second dilation. The cumulative probability of need for a second dilation following the index procedure was 33.6% at 1 year (95% CI, 25.9%-38.7%), 53.9% at 3 years (45.9%-61.2%), and 60.2% at 5 years (51.4%-67.5%). Six adverse events occurred after the first procedure: 4 perforations, 1 patient with bleeding, and 1 patient with abdominal pain requiring hospitalization. A total of 82 (30%) patients required surgery for their stricture. In a large cohort, endoscopic stricture dilation in CD was safe and effective. About 33% of patients required a second dilation at 1 year after the initial dilation; younger age and smaller inner diameter of the index stricture predicted need for a second dilation. 10.1093/ibd/izy049_video1izy049.video15794820307001.


Molecular mechanism of plant growth promotion and induced systemic resistance to tobacco mosaic virus by Bacillus spp.
Bacillus spp., as a type of plant growth-promoting rhizobacteria (PGPR), were studied with regards promoting plant growth and inducing plant systemic resistance. The results of greenhouse experiments with tobacco plants demonstrated that treatment with the Bacillus spp. significantly enhanced the plant height and fresh weight, while clearly lowering the disease severity rating of the tobacco mosaic virus (TMV) at 28 days post-inoculation (dpi). The TMV accumulation in the young non-inoculated leaves was remarkably lower for all the plants treated with the Bacillus spp. An RTPCR analysis of the signaling regulatory genes Coi1 and NPR1, and defense genes PR-1a and PR-1b, in the tobacco treated with the Bacillus spp. revealed an association with enhancing the systemic resistance of tobacco to TMV. A further analysis of two expansin genes that regulate plant cell growth, NtEXP2 and NtEXP6, also verified a concomitant growth promotion in the roots and leaves of the tobacco responding to Bacillus spp.


Acute Kidney Injury in the 2019 Novel Coronavirus Disease.
The 2019 novel coronavirus disease (CO-VID-19) is a newly defined serious infectious disease caused by the SARS-CoV-2 virus. The epidemic started in Wuhan, China, in December of 2019 and quickly spread to over 200 countries. It has affected 4,258,666 people, with 294,190 deaths worldwide by May 15, 2020. COVID-19 is characterized by acute respiratory disease, with 80% of patients presenting mild like flu-like symptoms; however, 20% of patients may have a severe or critical clinical presentation, which likely causes multiple organ injuries (e.g., kidney, heart, blood, and nervous system). Among them, acute kidney injury (AKI) is a critical complication due to its high incidence and mortality rate. Here we present a review of the current understanding of AKI in COVID-19. CO-VID-19 is a catastrophic contagious disease caused by the coronavirus, and the AKI induced by COVID-19 significantly increases the mortality rate. In this review, we summarize the clinical characteristics of COVID-19 induced AKI by focusing on its epidemiology, pathogenesis, clinical diagnosis, and treatment. Multiple studies have shown that COVID-19 may involve the kidneys and cause AKI. This article reviews the characteristics of COVID-19-induced AKI largely based on up-to-date studies in the hope that it will be helpful in the current global fight against and treatment of COVID-19.


Gaussian noise up-sampling is better suited than SMOTE and ADASYN for clinical decision making.
Clinical data sets have very special properties and suffer from many caveats in machine learning. They typically show a high-class imbalance, have a small number of samples and a large number of parameters, and have missing values. While feature selection approaches and imputation techniques address the former problems, the class imbalance is typically addressed using augmentation techniques. However, these techniques have been developed for big data analytics, and their suitability for clinical data sets is unclear.This study analyzed different augmentation techniques for use in clinical data sets and subsequent employment of machine learning-based classification. It turns out that Gaussian Noise Up-Sampling (GNUS) is not always but generally, is as good as SMOTE and ADASYN and even outperform those on some datasets. However, it has also been shown that augmentation does not improve classification at all in some cases.