Co-infection in patients with hypoxemic pneumonia due to COVID-19 in Reunion Island.
This study aimed to evaluate the incidence of co-infection with different types of pathogens in patients with hypoxemic pneumonia due to coronavirus disease 2019 (COVID-19) in Reunion Island.This observational study using a prospectively collected database of hypoxemic pneumonia due to COVID-19 cases was conducted at Félix Guyon University Hospital in Reunion Island, France.Between 18 March 2020 and 15 April 2020, 156 patients were admitted to our hospital for COVID-19. A total of 36 patients had hypoxemic pneumonia (23.1%) due to COVID-19. Thirty of these cases (83.3%) were imported by travelers returning mainly from metropolitan France and Spain. Patients were screened for co-infection with other pathogens at admission: 31 (86.1%) by multiplex polymerase chain reaction (PCR) and 16 (44.4%) by cytobacteriological examination of sputum culture. Five patients (13.9%) were found to have co-infection: 1 with influenza virus A H1N1 (pdm09) associated with Branhamella catarrhalis, 1 with Streptococcus pneumoniae associated with Haemophilus influenzae, 1 with Human Coronavirus 229E, 1 with Rhinovirus, and 1 with methicillin-susceptible Staphylococcus aureus. Patients with co-infection had higher D-dimer levels than those without co-infection (1.36 [1.34-2.36] μg/mL vs 0.63 [0.51-1.12] μg/mL, P = .05).The incidence of co-infection in our cohort was higher than expected (13.9%). Three co-infections (with influenza virus A(H1N1) pdm09, Streptococcus pneumoniae, and Staphylococcus aureus) required specific treatment. Patients with hypoxemic pneumonia due to COVID-19 should be screened for co-infection using respiratory cultures or multiplex PCR. Whilst our study has a number of limitations, the results from our study suggest that in the absence of screening, patients should be commenced on treatment for co-infection in the presence of an elevated D-dimer.


Recent advances in congenital ichthyoses.
In 2010, a new classification of the congenital ichthyoses was published. At the time, the causative genes were known in many but not all instances. The goal of this review is to provide an update on molecular and clinical findings in congenital ichthyosis and to revise evidence-based and emerging treatments. Mutations in genes encoding for desmosomal components have recently been shown to cause three clinically overlapping entities: peeling skin disease; severe dermatitis, multiple allergies and metabolic wasting syndrome; and Netherton syndrome. Mutations in keratin 10 have been identified as the cause of ichthyosis with confetti, a rare form of ichthyosis characterized by severe erythroderma in which healthy spots gradually develop since childhood. There is no curative treatment for the congenital ichthyoses. A recent systematic review of randomized clinical trials of ichthyosis treatments revealed that research evidence of therapy is poor. The expanding phenotype and genotype of the ichthyoses facilitates accurate clinical diagnosis and permits a deeper knowledge of the epidermal pathophysiology. Although curative treatment is yet to come, N-acetylcysteine has recently been added to the therapeutic armamentarium and topical enzyme replacement therapy has emerged as a promising alternative in TG1-deficient individuals.


Vessel suppressed chest Computed Tomography for semi-automated volumetric measurements of solid pulmonary nodules.
To evaluate whether vessel-suppressed computed tomography (VSCT) can be reliably used for semi-automated volumetric measurements of solid pulmonary nodules, as compared to standard CT (SCT) MATERIAL AND METHODS: Ninety-three SCT were elaborated by dedicated software (ClearRead CT, Riverain Technologies, Miamisburg, OH, USA), that allows subtracting vessels from lung parenchyma. Semi-automated volumetric measurements of 65 solid nodules were compared between SCT and VSCT. The measurements were repeated by two readers. For each solid nodule, volume measured on SCT by Reader 1 and Reader 2 was averaged and the average volume between readers acted as standard of reference value. Concordance between measurements was assessed using Lin's Concordance Correlation Coefficient (CCC). Limits of agreement (LoA) between readers and CT datasets were evaluated. Standard of reference nodule volume ranged from 13 to 366 mm3. The mean overestimation between readers was 3 mm3 and 2.9 mm3 on SCT and VSCT, respectively. Semi-automated volumetric measurements on VSCT showed substantial agreement with the standard of reference (Lin's CCC = 0.990 for Reader 1; 0.985 for Reader 2). The upper and lower LoA between readers' measurements were (16.3, -22.4 mm3) and (15.5, -21.4 mm3) for SCT and VSCT, respectively. VSCT datasets are feasible for the measurements of solid nodules, showing an almost perfect concordance between readers and with measurements on SCT.


Enhanced detection of sleep apnoea using heart-rate, respiration effort and oxygen saturation derived from a photoplethysmography sensor.
This paper presents a study on identifying sleep apnoea using the photoplethysmography (PPG) measurements, which is obtained from the SpO2 sensor. Using a database of polysomnogram (PSG) records of 52 patients, the heart rate and breathing effort information was derived from the PPG measurements and then features are extracted and processed by a classifier to detect one-minute epochs of sleep apnoea. The ground truth labels for the epochs were determined by trained technicians using the full PSG signal. Pulse oximetry (SpO2) measurements from the same sensor are also used in the classification process for comparison and in combination with the PPG results. The results show that both the heart rate and respiratory effort information derived from the PPG signal were able to detect apnoeic epochs with some success. The best classification performance of 87% for correctly labelling the epochs was obtained when the SpO2 features and the PPG features were combined.


[Effect of Electroacupuncture at Distal and Proximal Acupoints on Expression of Spinal p 38 Mitogen-activated Protein Kinase and Cyclic Adenosine 3',5'-monophosphate in Rats with Lumbago].
To observe the influence of Electroacupuncture (EA) stimulation of different distal-proximal acupoints combination groups on pain reaction, spinal p 38 mitogen-activated protein kinase (p 38 MAPK) expression and cyclic adenosine 3', 5'-monophosphate (cAMP) content in experimental lumbago rats. Seventy-eight male SD rats were randomized into normal, model, sham operation, EX-B 2-BL 25 (proximal acupoints, PA), BL 40-BL 60 (distal acupoints, DA) and DA+PA groups. The lumbago model was established by implanting the autologous nucleus pulposus to the site close to the left L 5 dorsal root ganglion and the surface of dura mate of spinal cord. EA (2 Hz/100 HZ,1-3 mA) was applied at bilateral EX-B 2-BL 25 or BL 40-BL 60 or both for 20 minutes, once daily for 7 days. The mechanical pain threshold was measured, and the expression of p 38 MAPK in the lumbar spinal cord was detected by immunohistochemistry and Western blot, separately. The content of cAMP in spinal cord (L 4-L 6) was measured by enzyme-linked immunosorbent assay (ELISA). After mode-ling, the mechanical pain threshold percentages were significantly decreased on day 3, 5 and 7 (P<0.01), and after EA stimulation of DA,PA and DA+PA, the decreased pain threshold was significantly increased at the 3 time-points (P<0.01), and the effects of both PA and DA+PA were markedly superior to that of DA (P<0.05, P<0.01). Following modeling, lumbar spinal p 38 MAPK immunoactivity and protein expression, and cAMP content were obviously up-regulated (P<0.01). Compared with the model group, the levels of p 38 MAPK immunoactivity and protein expression in the 3 EA groups and the sham group, and cAMP contents in both PA and DA+PA groups (not in the DA and sham groups) were considerably down-regulated (P<0.01, P<0.05). EA stimulation of distal+proximal acupoints and proximal acupoints near the focus can raise pain threshold in lumbago rats, which may be associated with their effects in suppressing lumbago-induced increase of expression of spinal p 38 MAPK protein and cAMP content. The effects of EA of distal+proximal acupoints and proximal acupoints are better than those of EA of simple distal acupoints.


Degradation of 40 selected pharmaceuticals by UV/H2O2.
The occurrence of pharmaceuticals in source waters is increasing. Although UV advanced oxidation is known to be an effective barrier against micropollutants, degradation rates are only available for limited amounts of pharmaceuticals. Therefore, the degradation of a large group of pharmaceuticals has been studied in this research for the UV/H2O2 process under different conditions, including pharmaceuticals of which the degradation by UV/H2O2 was never reported before (e.g., metformin, paroxetine, pindolol, sotalol, venlafaxine, etc.). Monochromatic low pressure (LP) and polychromatic medium pressure (MP) lamps were used for three different water matrices. In order to have well defined hydraulic conditions, all experiments were conducted in a collimated beam apparatus. Degradation rates for the pharmaceuticals were determined. For those compounds used in this research that are also reported in literature, measured degradation results are in good agreement with literature data. Pharmaceutical degradation for only photolysis with LP lamps is small, which is increased by using a MP lamp. Most of the pharmaceuticals are well removed when applying both UV (either LP or MP) and H2O2. However, differences in degradation rates between pharmaceuticals can be large. For example, ketoprofen, prednisolone, pindolol are very well removed by UV/H2O2, whereas metformin, cyclophosphamide, ifosfamide are very little removed by UV/H2O2.


Endogenous ethylene production is a potential problem in the measurement of nitrogenase activity associated with excised corn and sorghum roots.
Endogenous ethylene production was evaluated as a source of ethylene during acetylene reduction assays with freshly collected roots of field-grown corn, Zea mays L. cv Funks G-4646, and sorghum, Sorghum bicolor (L.) Moench. cv CK-60A. Ethylene production was not detected when roots were incubated in air without acetylene. The presence of endogenous ethylene production was confirmed when roots were incubated anaerobically and in the presence of 40 millimolar sodium hydrosulfite. Ethylene oxidase activity was also associated with excised roots. The rate of ethylene oxidation was higher than the rates of ethylene accumulation during either acetylene reduction assays or anaerobic incubations. These results indicate that the procedure of incubating roots of grasses in air to monitor endogenous ethylene production is not a valid control in acetylene reduction studies with grasses. The presence of endogenous ethylene production during acetylene reduction assays was demonstrated by using either CO to inhibit nitrogenase activity or chloramphenicol to inhibit nitrogenase synthesis in freshly excised roots.


[Comparative study of a rapid testing with real time RT-PCR for diagnosis of influenza AH1N1 2009].
Compare QuickVue Influenza A+B test with real-time RT-PCR for the diagnosis of influenza AH1N1 2009. Retrospective-comparative study of 135 respiratory specimens from individuals with symptoms of influenza processed from May 2009 to October 2010.The above mentioned tests were performed simultaneously. For statistic analysisthe softwareof Confidence IntervalAnalysis 2000 was used. The parameters obtained were: sensitivity 62.96; specificity 94.44; negative predictive value 62.9; positive predictive value 94.44; positive likelihood ratio 11.33; negative likelihood ratio 0.39. Confidence intervals to 95,were calculated to all of the above data. The test QuickVue InfluenzaA+B is a rapid,simple test,with lower cost than real-time RT-PCR useful for identifying the type of virus outbreaks of influenza in a given population.It correlates well with more specific test and similar reports.


Effect of carvedilol on coronary flow reserve in patients with hypertensive left-ventricular hypertrophy.
Patients with hypertensive left-ventricular hypertrophy (LVH) have lower coronary flow reserve (CFR). Whether carvedilol can improve CFR of patients with hypertensive LVH is unknown. We aimed to investigate the effects of carvedilol on CFR in patients with hypertensive LVH. Sixty-three patients were randomly divided into two groups for treatment with carvedilol or metoprolol. The peak diastolic coronary flow velocity in the left anterior descending coronary artery at rest and at maximal vasodilation with dipyridamole infusion was recorded by transesophageal echocardiography (TEE), then CFR was calculated at baseline and at the end of 6 months of therapy. Left-ventricular mass index (LVMI) was calculated by 2-D echocardiography. Endothelium-dependent and -independent reactivity of the brachial artery was measured. Levels of plasma endothelin-1 (ET1), nitric oxide (NO) and other metabolites were monitored and analyzed before and after 6-month therapy. Both blood pressure and heart rate decreased significantly in the two treatment groups after therapy (p<0.05). With carvedilol treatment, LVMI was lower (p<0.05), endothelium function of the brachial artery was higher (p<0.05), and peak diastolic coronary flow velocity at rest and at maximal vasodilation after dipyridamole infusion was significantly higher (p<0.05) than with metoprolol treatment, which led to a significantly higher CFR (p<0.05). Changes in CFR and LVMI with carvedilol treatment were inversely correlated (R(2)=0.474, p=0.036). With carvedilol treatment, plasma level of ET-1 was lower, but that of NO was significantly higher than with metoprolol treatment (both p<0.05). The CFR of patients with hypertensive LVH but not coronary artery disease could increase with 6-month carvedilol therapy.


Silencing Doublesex expression triggers three-level pheromonal feminization in Nasonia vitripennis males.
Doublesex (Dsx) has a conserved function in controlling sexual morphological differences in insects, but our knowledge of its role in regulating sexual behaviour is primarily limited to Drosophila. Here, we show with the parasitoid wasp Nasonia vitripennis that males whose Dsx gene had been silenced (NvDsx-i) underwent a three-level pheromonal feminization: (i) NvDsx-i males were no longer able to attract females from a distance, owing to drastically reduced titres of the long-range sex pheromone; (ii) NvDsx-i males were courted by wild-type males as though they were females, which correlated with a lower abundance of alkenes in their cuticular hydrocarbon (CHC) profiles. Supplementation with realistic amounts of synthetic (Z)-9-hentriacontene (Z9C31), the most significantly reduced alkene in NvDsx-i males, to NvDsx-i males interrupted courtship by wild-type conspecific males. Supplementation of female CHC profiles with Z9C31 reduced courtship and mating attempts by wild-type males. These results prove that Z9C31 is crucial for sex discrimination in N. vitripennis; and (iii) Nvdsx-i males were hampered in eliciting female receptivity and thus experienced severely reduced mating success, suggesting that they are unable to produce the to-date unidentified oral aphrodisiac pheromone reported in N. vitripennis males. We conclude that Dsx is a multi-level key regulator of pheromone-mediated sexual communication in N. vitripennis.


Glycogen synthase deficiency (glycogen storage disease type 0) presenting with hyperglycemia and glucosuria: report of three new mutations.
Although glycogen storage disease type 0 (GSD0) is included in the differential diagnosis of ketotic hypoglycemia, it usually is not considered in the evaluation of glucosuria or hyperglycemia. We describe two children with GSD0, confirmed by mutation analysis, who had glucosuria and hyperglycemia. Because of the variable presentation of this disorder and previous dependence on liver biopsy to confirm diagnosis, it is likely that GSD0 is underdiagnosed.


Effect of clinical mutations on functionality of the human riboflavin transporter-2 (hRFT-2).
The Brown-Vialetto-Van Laere syndrome (BVVLS) is a rare neurological disease characterized by ponto-bulbar palsy, bilateral sensorineural deafness, and respiratory insufficiency. Recent genetic studies have identified mutations in the C20orf54 gene, which encodes the human riboflavin (RF) transporter -2 (hRFT-2) and suggested their link to the manifestation of BVVLS. However, there is nothing currently known about the effect of these mutations on functionality of hRFT-2, a protein that is expressed in a variety of tissues with high expression in the intestine. We addressed this issue using the human-derived intestinal epithelial Caco-2 cells. Our results showed significant (P<0.01) impairment in RF uptake by Caco-2 cells transiently expressing W17R, P28T, E36K, E71K, and R132W (but not L350M) hRFT-2 mutants. This impairment in RF transport was not due to a decrease in transcription and/or translation of hRFT-2, since mRNA and protein levels of the carrier were similar in cells expressing the mutants and wild-type hRFT-2. Confocal images of live Caco-2 cells transiently transfected with hRFT-2 mutants (fused with green fluorescent protein) showed the P28T, E36K, E71K, and R132W mutants were retained within the endoplasmic reticulum, while the W17R and L350M mutants were expressed at the cell membrane; cell surface expression of the W17R mutant was further confirmed by direct determination of cell surface transporter density. These results show for the first time that some of the BVVLS associated mutations in hRFT-2 affect the transporter functionality and that this effect is mediated via alterations in membrane targeting and/or activity of the transporter.


Phosphorylation of Marburg virus NP region II modulates viral RNA synthesis.
Phosphorylation of the Marburg virus nucleoprotein NP is distributed over 7 regions (I-VII) in its C-terminus. The exact localization of phosphorylated amino acids and function of NP phosphorylation are unknown. Here, we show that the major phosphate acceptor sites in NP region II are serine 446 and serines 453-455; the latter are located in a cluster of 6 serine residues (aa 450-455). The function of phosphorylation in region II was tested using an infectious virus-like particle assay. Phosphorylation influenced reporter gene activity that reflects viral transcription and replication. An NP mutant mimicking 3 phosphorylated serine residues at position 453-455 supported reporter gene activity better than wild-type NP. Negative charges at positions 450-452 and when the serine cluster was completely substituted by alanine inhibited reporter gene activity significantly. These data support the idea that phosphorylation of NP region II modulates viral RNA synthesis in transcription and/or replication.


Endometriosis causing intussusception of the ileum into the colon.
Intussusception of the caecum occurs about twenty times less frequently in adults as compared to children and in 90% of these cases is caused by intestinal tumors. Intussusception of the ileum usually causes intestinal obstruction which requires urgent surgical intervention. So far only a few cases of intussusception due to the presence of endometrial tumor have been described. The clinical course, imaging and laboratory tests are not specific for endometriosis. The macroscopic appearance of the tumor during laparotomy is also not diagnostic. In case of endometriosis, the diagnosis can only be made on the basis of the histopathological examination of the excised tumor In this report, we present the diagnostic process and treatment of a patient with intussusception of the ileum to the ascending and transverse colon due to cecal tumor During the operation, the surgeon suspected a cancerous tumor and performed a right hemicolectomy The final diagnosis of endometriosis was made on the basis of the histopathological analysis.


Oxygen free radicals and pelvic adhesion formation: II. The interaction of oxygen free radicals and adhesion-preventing solutions.
A three-part animal and in vitro study gives evidence that oxygen free radicals are produced by intraperitoneal macrophages in response to pelvic surgery. These macrophages appear to ingest high-molecular-weight substances used to prevent adhesions (such as 32% dextran 70 and carboxymethylcellulose). However, the production of oxygen free radicals is not enhanced by the presence of 32% dextran 70 or carboxymethyl cellulose.


NCAM1 and GDF15 are biomarkers of Charcot-Marie-Tooth disease in patients and mice.
Molecular markers scalable for clinical use are critical for the development of effective treatments and the design of clinical trials. Here, we identify proteins in sera of patients and mouse models with Charcot-Marie-Tooth disease (CMT) with characteristics that make them suitable as biomarkers in clinical practice and therapeutic trials. We collected serum from mouse models of CMT1A (C61 het), CMT2D (GarsC201R, GarsP278KY), CMT1X (Gjb1-null), CMT2L (Hspb8K141N) and from CMT patients with genotypes including CMT1A (PMP22d), CMT2D (GARS), CMT2N (AARS) and other rare genetic forms of CMT. The severity of neuropathy in the patients was assessed by the CMT Neuropathy Examination Score (CMTES). We performed multitargeted proteomics on both sample sets to identify proteins elevated across multiple mouse models and CMT patients. Selected proteins and additional potential biomarkers, such as growth differentiation factor 15 (GDF15) and cell free mitochondrial DNA, were validated by ELISA and quantitative PCR, respectively. We propose that neural cell adhesion molecule 1 (NCAM1) is a candidate biomarker for CMT, as it was elevated in Gjb1-null, Hspb8K141N, GarsC201R and GarsP278KY mice as well as in patients with both demyelinating (CMT1A) and axonal (CMT2D, CMT2N) forms of CMT. We show that NCAM1 may reflect disease severity, demonstrated by a progressive increase in mouse models with time and a significant positive correlation with CMTES neuropathy severity in patients. The increase in NCAM1 may reflect muscle regeneration triggered by denervation, which could potentially track disease progression or the effect of treatments. We found that member proteins of the complement system were elevated in Gjb1-null and Hspb8K141N mouse models as well as in patients with both demyelinating and axonal CMT, indicating possible complement activation at the impaired nerve terminals. However, complement proteins did not correlate with the severity of neuropathy measured on the CMTES scale. Although the complement system does not seem to be a prognostic biomarker, we do show complement elevation to be a common disease feature of CMT, which may be of interest as a therapeutic target. We also identify serum GDF15 as a highly sensitive diagnostic biomarker, which was elevated in all CMT genotypes as well as in Hspb8K141N, Gjb1-null, GarsC201R and GarsP278KY mouse models. Although we cannot fully explain its origin, it may reflect increased stress response or metabolic disturbances in CMT. Further large and longitudinal patient studies should be performed to establish the value of these proteins as diagnostic and prognostic molecular biomarkers for CMT.


Production of a cloned mouse by nuclear transfer from a fetal fibroblast cell of a mouse closed colony strain.
We have tested a closed colony mouse strain as a source for nuclei donors to determine differences in cloning efficiency. When donor nuclei were isolated from fetal fibroblast cells and injected into recipient oocytes from closed colony mice (ICR), reconstructed oocytes developed to full term and the success rate of cloning was 0.1%. This result indicates that cloning efficiency does not depend on the cell type. The body weight of the cloned mouse was lighter than controls, and the lifetime of the cloned mouse was the average for a mouse. These results contradict commonly-held views on cloning.


Silica self-assembly and synthesis of microporous and mesoporous silicates.
The microstructure of silica in basic aqueous solutions containing organic cations and prepared from monomeric precursors is reviewed and interpreted within the context of classical ideas of self-assembly of molecular aggregates. The solution properties can be understood by using the pseudo-phase separation approach coupled to the acid-base chemistry of silanol groups and the Poisson-Boltzmann equation. The silica nanoparticles frequently observed in these systems have a core-shell structure with silica in the core and the organic cations at the shell. Individual particles are observed when the forces between particles are repulsive-as is the case for small cations such as tetramethylammonium or tetrapropylammonium-and extended structures such as M41S materials are formed when the forces are attractive--as is the case for surfactants such as cetyltrimethylammonium. These ideas are useful to understand the evolution of zeolite synthesis gels from nucleation to crystal growth. Although at room temperature the silica and the organic cations are segregated, upon heating the organic cations are embedded within the particles. This transformation signals the onset of structure direction whereby the size and geometry of the organic cation induce changes in the structure of silica that may lead to zeolite nuclei.


Editorial Perspective: A call to collective action - improving the implementation of evidence in children and young people's mental health.
With growing mental health needs of children and young people and the increasing demand on children and young people's mental health services, narrowing the evidence to practice implementation gap has never been more important. Implementation science and research provides useful theory, identification of barriers and facilitators as well as suggested strategies for improved uptake of evidence-based treatments, but the application of these is often limited. Supporting optimal learning and implementation cultures based on collaborative, relational and pragmatic action planning is likely key. We propose suggested next steps and recommendations to move this agenda forward within the children and young people's mental health field with a 'call to action'. With the need for specific roles and clear accountability, we emphasise that between clinicians, researchers, consumers and policy makers this is everyone's business.


Computational models for identifying potential P-glycoprotein substrates and inhibitors.
Multidrug resistance mediated by ATP binding cassette (ABC) transporters such as P-glycoprotein (P-gp) represents a serious problem for the development of effective anticancer drugs. In addition, P-gp has been shown to reduce oral absorption, modulate hepatic, renal, or intestinal elimination, and restrict blood-brain barrier penetration of several drugs. Consequently, there is a great interest in anticipating whether drug candidates are P-gp substrates or inhibitors. In this respect, two different computational models have been developed. A method for discriminating P-gp substrates and nonsubstrates has been set up based on calculated molecular descriptors and multivariate analysis using a training set of 53 diverse drugs. These compounds were previously classified as P-gp substrates or nonsubstrates on the basis of the efflux ratio from Caco-2 permeability measurements. The program Volsurf was used to compute the compounds' molecular descriptors. The descriptors were correlated to the experimental classes using partial least squares discriminant analysis (PLSD). The model was able to predict correctly the behavior of 72% of an external set of 272 proprietary compounds. Thirty of the 53 previously mentioned drugs were also evaluated for P-gp inhibition using a calcein-AM (CAM) assay. On the basis of these additional P-gp functional data, a PLSD analysis using GRIND-pharmacophore-based descriptors was performed to model P-gp substrates having poor or no inhibitory activity versus inhibitors having no evidence of significant transport. The model was able to discriminate between 69 substrates and 56 inhibitors taken from the literature with an average accuracy of 82%. The model allowed also the identification of some key molecular features that differentiate a substrate from an inhibitor, which should be taken into consideration in the design of new candidate drugs. These two models can be implemented in a virtual screening funnel.


Study on the effect of polysaccharides from Solanum nigrum Linne on cellular immune function in tumour-bearing mice.
We investigated the anti-tumour effect of polysaccharides from Solanum nigrum Linne, and its relationship with the immune function of tumour-bearing organisms. MTT assay was used to observe the effect of different doses of polysaccharides from Solanum nigrum Linne on proliferation of lymphocytes in tumour-bearing mice. ELISA assay was also used to detect the levels of IL-2 in mice, and a laser scanning confocal microscope was used to detect the effect of polysaccharides from Solanum nigrum Linne on intralymphocytic free calcium ion concentration in tumour-bearing mice. Different doses of polysaccharides from Solanum nigrum Linne significantly inhibited the growth of mouse H22 solid tumours, improved the survival time of tumour-bearing mice, increased the proliferation of lymphocytes, elevated the levels of IL-2, and increased the concentration of calcium ions in the lymphocytes. Polysaccharides from Solanum nigrum Linne have certain anti-tumour effect, which is related with the cellular immune function that regulates the body.


Switch Off Totally or Switch Off Strategically? The Consequences of Thinking About Work on Job Performance.
As a universal workplace phenomenon, the impact of work-related rumination on job performance is attracting scholars' attention. In the current study, the relationship between two types of work-related rumination, counterproductive behavior, and creativity at work were examined, as well as the mechanism of this association. Participants were 1109 employees from a variety of jobs in mainland China. The results showed that affective rumination was negatively associated with employees' work creativity and positively associated with counterproductive behavior. On the contrary, problem-solving pondering was positively related to creativity and negatively related to counterproductive behavior. The loss of self-control resource partially mediated the link between affective rumination and counterproductive behavior. Problem-solving pondering had no significant impact on self-control resource. Results suggest the significant effects of problem-solving pondering may be positive in the workplace and clarify the self-control resource is the internal mechanism linking rumination and job performance.


Detection of activity limitations in older adults with MCI or Alzheimer's disease through evaluation of perceived difficulty in use of everyday technology: a replication study.
Earlier research indicates that the ability to use everyday technology (ET) may be sensitive to subtle functional change. People with mild cognitive impairment (MCI) have been identified as significantly more disabled in ET use compared to controls, albeit less disabled than people with dementia. The aim of this study was to investigate the replicability of these findings using an improved version of the Everyday Technology Use Questionnaire (ETUQ) to compare perceptions of relevance and difficulty in ET use in participants with MCI or Alzheimer's disease (AD) and controls. Additional aims were to explore the validity of ETUQ, and the relationships between perceived difficulty in ET use and cognitive status, mood state, and involvement in everyday life activities. In total, 118 participants were included, 37 with AD, 37 with MCI, and 44 controls. Analyses confirmed that the rating scale of the ETUQ functioned well. The three groups overlapped but differed significantly in their perceptions of ETs relevance (p < 0.05) as well as of difficulties in ET use (p < 0.001). Moderate correlations were also found between ETUQ measures and cognitive status, mood, and involvement in activities, the strongest being that between ETUQ measures and involvement in activities (r = 0.563). Taken together, the findings underscore the plausibility of disability already in people with MCI, as the use of ET strongly correlates to involvement in activities. It is therefore important that professionals who meet older adults with cognitive impairment take this aspect of function into account in assessments and targeted interventions.


The analysis of the ethical, organizational and legal aspects of Polish biobanks activity.
Biobanks create new opportunities for the public health (Public Health Genomics) but need some regulations. Polish biobanks are in the phase of dynamic transformations aiming at integrating their activity and adjusting them to the international standards. The aim of this article is to present the current standards held in the most important Polish institutions collecting biological samples. A survey was conducted by the questionnaire filled by managers and directors of 24 Polish biobanks. Questions concerned obtaining patient informed consent (also a consent to some future researches and access to dates by other organizations), protection of privacy, storage of the samples and the relevant information, the opinion related to the need of establishing Polish national DNA data bank and possibilities of the scientific international cooperation. The written consent to carry out research on the samples is obtained almost everywhere, but 29% of biabanks does not acquire the consent for the future usage of the samples. Almost all inquired banks (93%, n = 22) declare the willingness to start an international cooperation. Most of respondents support the idea of establishing the Polish national DNA bank by the fusion of the already existing banks. The inquiry findings point that the current biobanks procedures do not differ to any relevant degree from procedures applied in the West European countries. Many of Polish biobanking organizations are willing to cooperate with foreign sites. It may enhance the European biobanking network and gene-environmental research.


Treatments in depression.
Major depression is believed to be a multifactorial disorder involving predisposing temperament and personality traits, exposure to traumatic and stressful life events, and biological susceptibility. Depression, both unipolar and bipolar, is a "phasic" disease. Stressful life events are known to trigger depressive episodes, while their influence seems to decrease over the course of the illness. This suggests that depression is associated with progressive stress response abnormalities, possibly linked to impairments of structural plasticity and cellular resilience. It therefore appears crucial to adequately treat depression in the early stages of the illness, in order to prevent morphological and functional abnormalities. While evidence suggests that a severely depressed patient needs antidepressant drug therapy and that a non-severely depressed patient may benefit from other approaches (ie, "nonbiological"), little research has been done on the effectiveness of different treatments for depression. The assertion that the clinical efficacy of antidepressants is comparable between the classes and within the classes of those medications may be true from a statistical viewpoint, but is of limited value in practice. The antidepressant drugs may produce differences in therapeutic response and tolerability. Among the possible predictors of outcome in depression treatment, those derived from clinical assessment, neuroendocrine investigations, polysomnographic sleep parameters, genetic variables, and brain imaging techniques have been extensively studied. This article also reviews therapeutic strategies used when initial treatment fails, and describes briefly new concepts in antidepressant therapies such as the regulation of disturbances in circadian rhythms. The treatment of depressive illness does not stop with treatment of acute episodes, and has to be envisaged as a continuous therapeutic intervention, of which we are still not able to determine the optimal duration of treatment and the moment that it should be ceased.


The effects of gonadotropin treatment on the immunological features of male patients with idiopathic hypogonadotropic hypogonadism.
There is a significant line of evidence for a role of androgens in the modulation of the immune system. However, little is known about immunological features of male patients with idiopathic hypogonadotropic hypogonadism (IHH) and the potential effects of gonadotropin treatment. Thus, the objective of this study was to evaluate the levels of selected soluble immune parameters [IgA, IgG, IgM, C3c, C4, interleukin-2 (IL-2), and IL-4], the CD4+/CD8 ratio, and counts of total lymphocyte and some subpopulation of lymphocytes (CD3+, CD4+, CD8+, and CD19+ cells) before and after gonadotropin treatment in men with IHH. Twenty-nine IHH patients and 19 age-matched healthy controls were included in the study. The patients were treated with human menopausal gonadotropin/hCG for 6 months. The pretreatment levels of serum Igs, C3c, IL-2, and IL-4 in the patients were significantly higher than those in the controls (P<0.001 for all). After treatment, all Igs (P<0.001), C3c (P<0.01), and IL-2 and IL-4 levels (P<0.005) were decreased significantly compared to pretreatment levels. Pretreatment lymphocyte counts (P<0.05); the percentages of CD3+ cells (P<0.001), CD4+ cells (P< 0.001), and CD19+ cells (P<0.001); and the CD4/CD8+ ratio in the patient group were significantly higher (P<0.05) than those in the controls. After treatment, the lymphocyte count (P<0.001); CD3+ (P<0.01), CD4+ (P<0.001), and CD19+ (P<0.005) cells; and the CD4-/CD8+ ratio (P<0.001) were decreased, but CD8+ cells were increased significantly (P<0.001). In summary, lack of testosterone action results in the enhancement of cellular and humoral immunity. The results of this study allowed us to conclude that testosterone deficiency affects both cell-mediated and humoral immunity, and these may be modulated with gonadotropin therapy in male patients with IHH.


Willingness to Receive COVID-19 Vaccination among Older Adults in Saudi Arabia: A Community-Based Survey.
Identifying the factors driving vaccine hesitancy can improve vaccine attitudes and motivate individuals to have the recommended vaccinations. However, failure to address the issue directly, or worse, ignoring it, could deepen such concerns, resulting in lower vaccination rates, leading to elevated rates of illness and vaccine-preventable deaths among older adults. The aim of this study was to explore the rate of acceptance of the COVID-19 vaccine among older adults in Saudi Arabia, along with the associated predicting factors and reasons for hesitancy. This study extracted data from a cross-sectional online survey on the acceptability of COVID-19 vaccination in Saudi Arabia, which was conducted from 8 to 14 December 2020. The sample of the study included 488 older adults aged 50 and older. The major data analytic tools employed in the study were bivariate and multivariable regression analyses. Among the 488 participants, 214 (43.85%) reported willingness to accept the COVID-19 vaccine when available. Older men were more likely to be willing to be vaccinated (adjusted odds ratio (aOR): 2.277; 95% confidence interval (CI): 1.092-4.745) than older women. High levels of education were significantly associated with willingness to be vaccinated. Older adults who had previously refused any vaccine were less likely to take the COVID-19 vaccine (aOR: 0.358; 95% CI: 0.154-0.830). Those who expressed a high or very high level of concern related to becoming infected were more likely to accept the vaccine against COVID-19 (aOR: 4.437; 95% CI: 2.148-9.168). Adverse side effects (27.01%), and safety and efficacy concerns (22.63%) were the most commonly cited reasons for vaccine hesitancy. The vaccination acceptance rate among older adults in Saudi Arabia is low. Interventions designed specifically for older adults addressing worries and concerns related to the vaccine are of paramount importance. In particular, these interventions should be tailored to address gender-based and health literacy level differences.


Primary bone adult T cell lymphoma with multiple skeletal lesions and debilitating painful osteolysis: a case report.
There have been only a limited number of reports on primary adult T cell lymphoma/leukemia (ATL) in the bone. This is a case report of a 75-year-old patient initially reporting multiple bone pains that were attributed to osteolytic ATL. The patient developed spontaneous chest/back pain and visited a local hospital. Laboratory tests showed high levels of alkaline phosphatase (ALP), and computed tomography (CT) revealed skeletal lesions with osteolysis. Although multiple myeloma was initially suspected, the results of bone marrow aspiration and bone biopsy were inconsistent. After he was referred to our hospital, mild hypercalcemia (10.4 mg/dL) with low-normal intact parathyroid hormone (PTH) (27 pg/mL), low parathyroid hormone-related protein (PTHrP), and elevated 1,25-dihydroxy vitamin D (1,25OH2D) levels (136 pg/mL) narrowed the differential diagnosis down to lymphomatous and granulomatous diseases, and then, the high serum soluble IL-2 receptor (3,450 U/mL) and the flower cells recognized in the peripheral blood sample suggested the involvement of ATL. Finally, the reevaluation of the iliac bone biopsy sample led us to the histological diagnosis of ATL infiltration in the bone. The subsequent two courses of chemotherapy in addition to denosumab resulted in an objective partial metabolic response indicated in 18-fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Although very rare, the bone involvement of ATL could be used for the differential diagnosis for local osteolytic bone pain in addition to multiple myeloma and metastatic bone diseases.


Influence of different staining beverages on color stability, surface roughness and microhardness of silorane and methacrylate-based composite resins.
To investigate the influence of different staining beverages on color stability, surface roughness and microhardness of silorane and methacrylate-based composite resins. Three different composite resins (Filtek Silorane, Filtek P60, Filtek Supreme XT) were tested. Thirty cylindrical specimens (10 × 2 mm) per material were prepared and polished with a series of aluminum-oxide polishing disks. Each group was then randomly subdivided into three groups according to the test beverages: distilled water (control), cola and coffee. The samples were immersed into different beverages for 15 days. Color, surface roughness and microhardness values were measured by a spectrophotometer, prophylometer and Vickers hardness device respectively, at baseline and after 15 days. The data were subjected to statistical analysis. Immersion in coffee resulted in a significant discoloration for all the composites tested, although the color change was lower in Filtek Silorane than that of MBCs (p < 0.05). All the composites tested showed similar surface roughness changes after immersion in different beverages (p > 0.05). Besides coffee caused more roughness change than others. Immersion in coffee caused highest microhardness change in Filtek Supreme XT (p < 0.05). Cola and coffee altered, to some degree, the color, surface roughness and/or microhardness of the tested resin composites, depending on the characteristics of the materials.


Audiovisual non-verbal dynamic faces elicit converging fMRI and ERP responses.
In an everyday social interaction we automatically integrate another's facial movements and vocalizations, be they linguistic or otherwise. This requires audiovisual integration of a continual barrage of sensory input-a phenomenon previously well-studied with human audiovisual speech, but not with non-verbal vocalizations. Using both fMRI and ERPs, we assessed neural activity to viewing and listening to an animated female face producing non-verbal, human vocalizations (i.e. coughing, sneezing) under audio-only (AUD), visual-only (VIS) and audiovisual (AV) stimulus conditions, alternating with Rest (R). Underadditive effects occurred in regions dominant for sensory processing, which showed AV activation greater than the dominant modality alone. Right posterior temporal and parietal regions showed an AV maximum in which AV activation was greater than either modality alone, but not greater than the sum of the unisensory conditions. Other frontal and parietal regions showed Common-activation in which AV activation was the same as one or both unisensory conditions. ERP data showed an early superadditive effect (AV > AUD + VIS, no rest), mid-range underadditive effects for auditory N140 and face-sensitive N170, and late AV maximum and common-activation effects. Based on convergence between fMRI and ERP data, we propose a mechanism where a multisensory stimulus may be signaled or facilitated as early as 60 ms and facilitated in sensory-specific regions by increasing processing speed (at N170) and efficiency (decreasing amplitude in auditory and face-sensitive cortical activation and ERPs). Finally, higher-order processes are also altered, but in a more complex fashion.


Trypsin inhibition by macrocyclic and open-chain variants of the squash inhibitor MCoTI-II.
MCoTI-I and MCoTI-II from the seeds of Momordica cochinchinensis are inhibitors of trypsin-like proteases and the only known members of the large family of squash inhibitors that are cyclic and contain an additional loop connecting the amino- and the carboxy-terminus. To investigate the contribution of macrocycle formation to biological activity, we synthesized a set of open-chain variants of MCoTI-II that lack the cyclization loop and contain various natural and non-natural amino acid substitutions in the reactive-site loop. Upon replacement of P1 lysine residue #10 within the open-chain variant of MCoTI-II by the non-natural isosteric nucleo amino acid AlaG [beta-(guanin-9-yl)-L-alanine], a conformationally restricted arginine mimetic, residual inhibitory activity was detected, albeit reduced by four orders of magnitude. While the cyclic inhibitors MCoTI-I and MCoTI-II were found to be very potent trypsin inhibitors, with picomolar inhibition constants, the open-chain variants displayed an approximately 10-fold lower affinity. These data suggest that the formation of a circular backbone in the MCoTI squash inhibitors results in enhanced affinity and therefore is a determinant of biological activity.


Varying Photoperiod, Ribulose 1,5-Bisphosphate Carboxylase/Oxygenase and CO(2) Uptake in Thalassiosira fluviatilis (Bacillariophyceae).
The purpose of this research was to test the hypothesis that acclimation of the unicellular marine alga, Thalassiosira fluviatilis Hustedt, to short photoperiods results in decreased cellular concentrations of ribulose 1,5-bisphosphate carboxylase/oxygenase and decreased rates of light-saturated CO(2) uptake. Cells were acclimated to photoperiods of 6:18, 12:12, and 18:6 h:h light:dark, and concentrations of the large subunit of the enzyme and responses of CO(2) uptake to varying irradiance were measured. Concentrations of the large subunit, which weighed approximately 50 kilodaltons, were conserved while rates of CO(2) uptake under light saturation and limitation, and cellular contents of chlorophyll a increased as photoperiod decreased. Apparently, these cells acclimate to short photoperiods by increasing rates of CO(2) uptake under saturating irradiances by increasing in vivo activation of ribulose 1,5-bisphosphate carboxylase/oxygenase. Also, chlorophyll-specific concentrations and specific activities of the enzyme appear to be lower and higher, respectively, in diatomaceous algae than in higher plants.


Recovering evolutionary trees under a more realistic model of sequence evolution.
We report a new transformation, the LogDet, that is consistent for sequences with differing nucleotide composition and that have arisen under simple but asymmetric stochastic models of evolution. This transformation is required because existing methods tend to group sequences on the basis of their nucleotide composition, irrespective of their evolutionary history. This effect of differing nucleotide frequencies is illustrated by using a tree-selection criterion on a simple distance measure defined solely on the basis of base composition, independent of the actual sequences. The new LogDet transformation uses determinants of the observed divergence matrices and works because multiplication of determinants (real numbers) is commutative, whereas multiplication of matrices is not,except in special symmetric cases. The use of determinants thus allows more general models of evolution with a symmetric rates of nucleotide change. The transformation is illustrated on a theoretical data set (where existing methods select the wrong tree) and with three biological data sets: chloroplasts, birds/mammals (nuclear), and honeybees ( mitochondrial ) . The LogDet transformation reinforces the logical distinction between transformations on the data and tree-selection criteria. The overall conclusions from this study are that irregular A,C,G,T compositions are an important and possible general cause of patterns that can mislead tree-reconstruction methods, even when high bootstrap values are obtained. Consequently, many published studies may need to be reexamined.


Effect of vascular amyloid on white matter disease is mediated by vascular dysfunction in cerebral amyloid angiopathy.
We postulated that vascular dysfunction mediates the relationship between amyloid load and white matter hyperintensities (WMH) in cerebral amyloid angiopathy (CAA). Thirty-eight cognitively healthy patients with CAA (mean age 70 ± 7.1) were evaluated. WMH was quantified and expressed as percent of total intracranial volume (pWMH) using structural MRI. Mean global cortical Distribution Volume Ratio representing Pittsburgh Compound B (PiB) uptake (PiB-DVR) was calculated from PET scans. Time-to-peak [TTP] of blood oxygen level-dependent response to visual stimulation was used as an fMRI measure of vascular dysfunction. Higher PiB-DVR correlated with prolonged TTP (r = 0.373, p = 0.021) and higher pWMH (r = 0.337, p = 0.039). Prolonged TTP also correlated with higher pWMH (r = 0.485, p = 0.002). In a multivariate linear regression model, TTP remained independently associated with pWMH (p = 0.006) while PiB-DVR did not (p = 0.225). In a bootstrapping model, TTP had a significant indirect effect (ab = 0.97, 95% CI: 0.137-2.461), supporting that the association between PiB-DVR and pWMH is mediated by TTP response. There was no longer a direct effect independent of the hypothesized pathway. Our study suggests that the effect of vascular amyloid load on white matter disease is mediated by vascular dysfunction in CAA. Amyloid lowering strategies might prevent pathophysiological processes leading to vascular dysfunction, therefore limiting ischemic brain injury.


Left Anterior Thoracotomy Minimally Invasive Aortic Valve Replacement Following Left Pneumonectomy.
We report the case of a 59-year-old man referred for aortic valve replacement for severe, symptomatic aortic insufficiency who underwent a minimally invasive left anterior thoracotomy aortic valve replacement. This approach was facilitated by his history of a left pneumonectomy for lung cancer 7 years prior to presentation, which resulted in a significant left mediastinal shift. The cannulation strategy and exposure were analogous to what would be expected from a standard right anterior thoracotomy minimally invasive aortic valve replacement. The minimally invasive approach allowed for early extubation and mobilization in a patient with moderate baseline pulmonary dysfunction.


Geographic tongue treated with topical tacrolimus.
Geographic tongue, or benign migratory glossitis, is usually an asymptomatic inflammatory disorder of the tongue mucosa of unknown etiology. It is characterized by circinate, erythematous, ulcer-like lesions of the dorsum and lateral border of the tongue due to loss of filiform papillae of the tongue epithelium. Symptomatic treatments have not been evaluated rigorously. We describe herein two cases of adult patients with persistent and painful geographic tongue successfully treated with topical application of 0.1% tacrolimus ointment. To our knowledge, this is the first report of successful treatment with topical 0.1% tacrolimus for symptomatic geographic tongue. Clinical trials are needed to confirm the efficacy and the safety of topical tacrolimus in treating geographic tongue.


Preparation, Physicochemical Properties and Hemocompatibility of Biodegradable Chitooligosaccharide-Based Polyurethane.
The purpose of this study was to develop a process to achieve biodegradable chitooligosaccharide-based polyurethane (CPU) with improved hemocompatibility and mechanical properties. A series of CPUs with varying chitooligosaccharide (COS) content were prepared according to the conventional two-step method. First, the prepolymer was synthesized from poly(ε-caprolactone) (PCL) and uniform-size diurethane diisocyanates (HBH). Then, the prepolymer was chain-extended by COS in N,N-dimethylformamide (DMF) to obtain the weak-crosslinked CPU, and the corresponding films were obtained from the DMF solution by the solvent evaporation method. The uniform-size hard segments and slight crosslinking of CPU were beneficial for enhancing the mechanical properties, which were one of the essential requirements for long-term implant biomaterials. The chemical structure was characterized by FT-IR, and the influence of COS content in CPU on the physicochemical properties and hemocompatibility was extensively researched. The thermal stability studies indicated that the CPU films had lower initial decomposition temperature and higher maximum decomposition temperature than pure polyurethane (CPU-1.0) film. The ultimate stress, initial modulus, and surface hydrophilicity increased with the increment of COS content, while the strain at break and water absorption decreased, which was due to the increment of crosslinking density. The results of in vitro degradation signified that the degradation rate increased with the increasing content of COS in CPU, demonstrating that the degradation rate could be controlled by adjusting COS content. The surface hemocompatibility was examined by protein adsorption and platelet adhesion tests. It was found that the CPU films had improved resistance to protein adsorption and possessed good resistance to platelet adhesion. The slow degradation rate and good hemocompatibility of the CPUs showed great potential in blood-contacting devices. In addition, many active amino and hydroxyl groups contained in the structure of CPU could carry out further modification, which made it an excellent candidate for wide application in biomedical field.


The relationship between mitral annular systolic velocity and ejection fraction in patients with preserved global systolic function of the left ventricle.
The aim of the study was to investigate the relationship between the ejection fraction (EF) and the mitral annular systolic velocity (Sm) in patients with preserved left ventricular systolic function (EF>55%). The study task was to evaluate whether the assessment of Sm(avg) can be used as an alternative to the Simpson's method in assessment of the EF. The expected benefit was that Sm could be used to predict EF, when EF is difficult to assess due to poor image quality (IQ). Sm was obtained by spectral pulse wave Tissue Doppler Imaging (pwTDI) from the lateral and septal sites of the mitral annulus (MA) and an averaged value was calculated - Sm(avg). EF was assessed using Simpson's rule. Participants were divided into controls (n=70), hypertensive (HTN, n=56), HTN with diastolic dysfunction (HTN/DD, n=65), HTN with diabetes mellitus (HTN/DM, n=52) and HTN with DD and DM (HTN/DD/DM, n=65). Sm(avg) showed strong correlation with EF (r=0.978; p<0.0001). There were no significant differences between the correlation coefficients between the subgroups and the controls. The mathematical model that the study recommended to assess the EF is: EF=45.0 + 2 × Sm(avg). The assessment of Sm(avg) could be used as an alternative to EF. This approach may be useful especially when the IQ is poor. The method maintains high accuracy and reproducibility in prediction of the EF.


Representation of multi-target activity landscapes through target pair-based compound encoding in self-organizing maps.
Activity landscape representations provide access to structure-activity relationships information in compound data sets. In general, activity landscape models integrate molecular similarity relationships with biological activity data. Typically, activity against a single target is monitored. However, for steadily increasing numbers of compounds, activity against multiple targets is reported, resulting in an opportunity, and often a need, to explore multi-target structure-activity relationships. It would be attractive to utilize activity landscape representations to aid in this process, but the design of activity landscapes for multiple targets is a complicated task. Only recently has a first multi-target landscape model been introduced, consisting of an annotated compound network focused on the systematic detection of activity cliffs. Herein, we report a conceptually different multi-target activity landscape design that is based on a 2D projection of chemical reference space using self-organizing maps and encodes compounds as arrays of pair-wise target activity relationships. In this context, we introduce the concept of discontinuity in multi-target activity space. The well-ordered activity landscape model highlights centers of discontinuity in activity space and is straightforward to interpret. It has been applied to analyze compound data sets with three, four, and five target annotations and identify multi-target structure-activity relationships determinants in analog series.


Augmented B lymphocyte response to antigen in the absence of antigen-induced B lymphocyte signaling in an IgG-transgenic mouse line.
IgG-containing B cell antigen receptor (IgG-BCR), the BCR mostly expressed on memory B cells, contains a distinct signaling function from IgM-BCR or IgD-BCR expressed on naïve B cells. Because naïve B cells transgenic for IgG exhibit augmented response to antigens similar to memory B cells, the distinct signaling function of IgG-BCR appears to play a role in augmented antibody responses of memory B cells. However, how IgG-BCR signaling augments B cell responses is not yet well understood. Here we demonstrate that B cells from IgG-transgenic mice are anergic with defect in generation of BCR signaling upon BCR ligation. However, these IgG-transgenic B cells generate markedly augmented antibody response to a T cell-dependent antigen, probably due to hyper-responsiveness to a T cell-derived signal through CD40. Both BCR signaling defect and augmented response to CD40 ligation are partially restored in xid IgG-transgenic mice in which BCR signaling is down-modulated due to a loss-of-function mutation in the tyrosine kinase Btk crucial for BCR signaling. Thus, IgG-BCR induces augmented B cell responses in the absence of antigen-induced BCR signaling probably through high ligand-independent BCR signaling that may "idle" B cells to make them ready to respond to T cell help. This finding strongly suggests a crucial role of ligand-independent signaling in receptor function.


Telomerase can inhibit the recombination-based pathway of telomere maintenance in human cells.
Telomere length can be maintained by telomerase or by a recombination-based pathway. Because individual telomeres in cells using the recombination-based pathway of telomere maintenance appear to periodically become extremely short, cells using this pathway to maintain telomeres may be faced with a continuous state of crisis. We expressed telomerase in a human cell line that uses the recombination-based pathway of telomere maintenance to test whether telomerase would prevent telomeres from becoming critically short and examine the effects that this might have on the recombination-based pathway of telomere maintenance. In these cells, telomerase maintains the length of the shortest telomeres. In some cases, the long heterogeneous telomeres are completely lost, and the cells now permanently contain short telomeres after only 40 population doublings. This corresponds to a telomere reduction rate of 500 base pairs/population doubling, a rate that is much faster than expected for normal telomere shortening but is consistent with the rapid telomere deletion events observed in cells using the recombination-based pathway of telomere maintenance (Murnane, J. P., Sabatier, L., Marder, B. A., and Morgan, W. F. (1994) EMBO J. 13, 4953-4962). We also observed reductions in the fraction of cells containing alternative lengthening of telomere-associated promyelocytic leukemia bodies and extrachromosomal telomere repeats; however, no alterations in the rate of sister chromatid exchange were observed. Our results demonstrate that human cells using the recombination-based pathway of telomere maintenance retain factors required for telomerase to maintain telomeres and that once the telomerase-based pathway of telomere length regulation is engaged, recombination-based elongation of telomeres can be functionally inhibited.


Evaluation of Web-Based Continuing Professional Development Courses: Aggregate Mixed-Methods Model.
Many continuing professional development (CPD) Web-based programs are not explicit about underlying theory and fail to demonstrate impact. The aim of this study was to develop and apply an aggregate mixed-methods evaluation model to describe the paradigm, theoretical framework, and methodological approaches used to evaluate a CPD course in tobacco dependence treatment, the Training Enhancement in Applied Cessation Counseling and Health (TEACH) project. We evaluated the effectiveness of the 5-week TEACH Web-based Core Course in October 2015. The model of evaluation was derived using a critical realist lens to incorporate a dimension of utilitarian to intuitionist approaches. In addition, we mapped our findings to models described by Fitzpatrick et al, Moore et al, and Kirkpatrick. We used inductive and deductive approaches for thematic analysis of qualitative feedback and dependent samples t tests for quantitative analysis. A total of 59 participants registered for the course, and 48/59 participants (81%) completed all course requirements. Quantitative analysis indicated that TEACH participants reported (1) high ratings (4.55/5, where 5=best/excellent) for instructional content and overall satisfaction of the course (expertise and consumer-oriented approach), (2) a significant increase (P ˂.001) in knowledge and skills (objective-oriented approach), and (3) high motivation (78.90% of participants) to change and sustain practice change (management-oriented approach). Through the intuitionist lens, inductive and deductive qualitative thematic analysis highlighted three central themes focused on (1) knowledge acquisition, (2) recommendations to enhance learning for future participants, and (3) plans for practice change in the formative assessment, and five major themes emerged from the summative assessment: (1) learning objectives, (2) interprofessional collaboration, (3) future topics of relevance, (4) overall modification, and (5) overall satisfaction. In the current aggregate model to evaluate CPD Web-based training, evaluators have been influenced by different paradigms, theoretical lenses, methodological approaches, and data collection methods to address and respond to different needs of stakeholders impacted by the training outcomes.


Molecular genetic testing of polymorphisms associated with venous thrombosis: a review of molecular technologies.
The growing knowledge of genetic polymorphisms predisposing to venous thrombosis has increased the demand for genetic testing of associated risk factors. This has prompted the need for simple, fast, reliable, and cost-effective genotyping methods for identification of those mutations. In the past decade, a large variety of DNA mutation analysis methods have been developed for detection of genetic variants associated with venous thrombosis, including PCR-based and PCR-independent technologies. Each of these technologies possesses unique advantages, but all have a common goal of simplifying and expediting mutation analysis. This review describes some of the commonly used technologies and commercially available platforms employed in clinical laboratories for genetic testing of thrombophilia. The choice of a technology for each individual laboratory would primarily depend on the specific requirements for the assay's accuracy, reliability, speed, throughput, and cost-effectiveness.


Comparison of fetal lung maturation in fetuses with intrauterine growth restriction with control group, using lung volume, lung/liver and lung/muscle signal intensity and apparent diffusion coefficient ratios on different magnetic resonance imaging sequences.
To compare lung volume, lung apparent diffusion coefficient (ADC) and signal intensity ratio (SIR) on different magnetic resonance imaging (MRI) sequences between intrauterine growth restriction (IUGR) fetuses and the control group. 49 IUGR and 58 non-IUGR fetuses were imaged using 3 Tesla MRI units. Total lung volume (TLV), lung/liver SIR (LLSIR) and lung/muscle SIR (LMSIR) in T1 and T2-weighted sequences and lung/liver ADC ratio (LLADCR) and lung/muscle ADC ratio (LMADCR) were assessed. LLSIR and LMSIR were significantly higher in the T1-weighted sequence (p-value: .03) and LLADCR and LMADCR were significantly lower on diffusion-weighted imaging (DWI) in IUGR fetuses compared to the control group (p-value: .01). There was no significant difference in SIRs in the T2-weighted sequence between the two groups. Although TLV was increased with gestational age in both groups, it was significantly lower in the IUGR group (mean: 82 ± 22.7 ml vs. 110.8 ± 18 ml, p-value: <.001). The T1-weighted sequence and DWI seem to be better than the T2-weighted sequence for assessing the faint difference of lung maturity between groups. However, SIR differences were not as meaningful as TLV differences and this could be related to the complex maturation process in IUGR fetuses as the effect of higher endogenous corticosteroids.


The contribution of Juan Rosai to the pathology of soft tissue tumors.
The conceptual evolution in the field of soft tissue tumor pathology has been mostly driven by a relatively small group of individuals that includes giants of the past and the present such as James Ewing, Raffaele Lattes, Arthur Purdy Stout, Franz Enzinger, Sharon Weiss, Lennart Angervall, Harry Evans, Marku Miettinen, and Christopher Fletcher. Juan Rosai, not only exerted an immense impact on surgical pathology in general, but in consideration of his unique talent in identifying novel clinicopathologic entities, has also contributed remarkably to current understanding of mesenchymal neoplasms. The creation of desmoplastic small round cell tumor certainly ranks among his most relevant efforts, although he actually put his mark on a broad variety of soft tissue lesions, including vascular neoplasms. It would be impossible to include in a single article all the entities that he created or contributed to refine; therefore, this review is limited to a selection of what we believe represent true milestones.


Preferential radiosensitization to glioblastoma cancer stem cell-like cells by a Hsp90 inhibitor, N-vinylpyrrolidone-AUY922.
The present study examined the radiosensitization induced by a heat shock protein 90 inhibitor, N-vinylpyrrolidone (NVP)-AUY922, in CD133-positive cells in a hypoxic area of T98G spheroids. CD133-positive cells that are induced in the hypoxic microenvironment of spheroids have previously been reported to exhibit cancer stem cell-like properties. The present study used CD133-positive cells from a glioblastoma cell line (T98G) as cancer stem cell-like cells. CD133-positive and negative cells were sorted from T98G spheroids using fluorescence-activated cell sorting and used for colony formation assay. Colony formation assay results indicated that NVP-AUY922 enhanced radiosensitivity more strongly in CD133-positive cells compared with CD133-negative cells. This result showed that NVP-AUY922 was a preferential radiosensitization candidate targeting glioblastoma cancer stem cells. The mechanisms underlying radiosensitization by NVP-AUY922 are discussed in relation to the properties of cancer stem cells. Overall, HIF-1α inhibition by NVP-AUY922 may induce higher sensitization of cancer stem cells to radiation.


Mariner 6 and 7 ultraviolet spectrometers.
The ultraviolet spectrometers that observed the atmosphere of Mars in July and August of 1969 consist of a planetary coronagraph and an Ebert-Fastie monochromator. The spectral range 1100-4300 A was measured using two photomultiplier tubes, one with a cesium iodide photocathode, the other with a bialkali photocathode. These tubes were operated with fixed high voltage supplies and charge sensitive amplifiers. The instruments were calibrated by comparison with a tungsten lamp, a sodium salicylate screen, and a flowing nitric oxide cell. The instruments were able to satisfactorily reject off-axis light at a distance of 6600 km and measure the emission spectrum of the upper atmosphere 170 km above the surface.


Introducing an innovative method in team conferences.
An innovative method to structure multidisciplinary team conferences in rehabilitation medicine was developed: Rehabilitation Activities Profile report system (RAP-TEAM). Experiences with introduction of RAP-TEAM and the study of its effects on the satisfaction of professionals are described. RAP-TEAM was introduced in three teams. RAP-TEAM did not influence the satisfaction of professionals in two teams; satisfaction in the third team even decreased. Nevertheless, professionals report more benefits than disadvantages of RAP-TEAM. Several possible explanations for these results and the methodological problems with this kind of evaluation study are discussed. The most important explanation is that introduction of an innovative method should be allowed sufficient time before it could become effective. Recommendations for a successful introduction of innovative changes are made. All people concerned must be aware that a process of change is not simple, and needs the full attention of all.


Obstructive Sleep Apnea and Atrial Fibrillation.
Atrial fibrillation (AF) is the most common arrhythmia, increasing with age and comorbidities. Obstructive sleep apnea (OSA) is a chronic sleep disorder more common in older men. It has been shown that OSA is linked to AF. Nonetheless, the prevalence of OSA in patients with AF remains unknown because OSA is significantly underdiagnosed. This review, including 54,271 patients, carried out a meta-analysis to investigate the association between OSA and AF. We also performed a meta-regression to explore cofactors influencing this correlation. A strong link was found between these two disorders. The incidence of AF is 88% higher in patients with OSA. Age and hypertension independently strengthened this association, indicating that OSA treatment could help reduce AF recurrence. Further research is needed to confirm these findings. Atrial Fibrillation (AF) is the most common arrhythmia, increasing with age and comorbidities. Obstructive sleep apnea (OSA) is a regulatory respiratory disorder of partial or complete collapse of the upper airways during sleep leading to recurrent pauses in breathing. OSA is more common in older men. Evidence exists that OSA is linked to AF. Nonetheless, the prevalence of OSA in patients with AF remains unknown because OSA is underdiagnosed. In order to investigate the incidence of AF in OSA patients, we carried out a meta-analysis including 20 scientific studies with a total of 54,271 subjects. AF was present in 4801 patients of whom 2203 (45.9%) had OSA and 2598 (54.1%) did not. Of a total of 21,074 patients with OSA, 2203 (10.5%) had AF and 18,871 (89.5%) did not. The incidence of AF was 88% higher in patients with OSA. We performed a meta-regression to explore interacting factors potentially influencing the occurrence of AF in OSA. Older age and hypertension independently strengthened this association. The clinical significance of our results is that patients with OSA should be referred early to the cardiologist. Further research is needed for the definition of the mechanisms of association between AF and OSA.


Mixtures of protic ionic liquids and propylene carbonate as advanced electrolytes for lithium-ion batteries.
In this study we investigated the chemical-physical properties of mixtures containing the protic ionic liquid (PIL) N-butyl-pyrrolidinium bis(trifluoromethanesulfonyl)imide (PYRH4TFSI), propylene carbonate (PC) and lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) in view of their use as electrolytes for lithium-ion batteries (LIBs). We showed that these electrolytic solutions might display conductivity and viscosity comparable to those of conventional electrolytes. Depending on the amount of PIL present inside the mixtures, such mixtures might also display the ability to suppress the anodic dissolution of Al. Furthermore, we showed that the coordination of lithium ions by TFSI in PIL-PC mixtures appears to be different than the one observed for mixtures of PC and aprotic ionic liquids (AILs). When used in combination with a battery electrode, e.g. lithium iron phosphate (LFP), these mixtures allow the achievement of high performance also at a very high C-rate.


Prenatal ultrasound diagnosis of poland syndrome.
Poland syndrome is a congenital nongenetic anomaly characterized by unilateral chest wall hypoplasia, ipsilateral hand abnormalities, and hemivertebrae. It has not ben described so far in the fetus. The patient was referred for suspected left-arm hypomelia at 22 weeks of gestation. On ultrasonography, we confirmed the presence of severe left-sided hypomelia and detected an asymmetry of the rib cage and 3 thoracic hemivertebrae. The absence of heart defects led us to make the putative diagnosis of Poland syndrome. After termination of pregnancy, the diagnosis was confirmed by the pathologist. The possibility of diagnosing Poland syndrome in utero is important for proper management and counseling. If the syndrome is suspected in a fetus, counselors may refer to specific postnatal data to provide the couple with survival rates, treatment options, and results and morbidity figures. If the pregnancy is terminated, a detailed necropsy is warranted to confirm the diagnosis because familial transmission has been reported.


To explant or not to explant: an invasive and noninvasive monitoring protocol to determine the need of continued ventricular assist device support.
Predictors of myocardial recovery after ventricular assist device (VAD) implantation are not well defined. The authors report their current VAD weaning protocol. Between 2003 and 2006, 38 patients received VAD implants. The authors performed 5 tests in 4 patients in whom echocardiography findings suggested myocardial recovery after implant. The protocol consists of assessing symptoms, electrocardiographic findings, hemodynamics, and cardiac function at baseline and as VAD support is weaned. As a result, 3 patients passed the weaning protocol and were explanted. There has been no recurrence of heart failure 667, 752, and 1007 days after explant, respectively. One patient failed the protocol after 151 days of support because of low cardiac index during the protocol. This patient was transplanted. This current experience of VAD weaning protocol is a novel tool to identify candidates for successful VAD explantation.


Increased expression of annexin A3 is a mechanism of platinum resistance in ovarian cancer.
Resistance to platinum drugs has emerged as a major obstacle in the treatment of ovarian cancers. Through proteomic analysis, we have found that the expression of annexin A3, a member of the Ca(2+) and phospholipid-binding annexin family, is significantly increased in platinum-resistant ovarian cell lines. Anti-annexin A3 immunostaining indicated that cancers from platinum-resistant patients also possess higher levels of annexin A3 than those from platinum-sensitive patients. Although expression of annexin A3 made susceptible ovarian cancer cells more resistant to platinum, expression of antisense annexin A3 downregulated its expression and rendered the resistant cells more sensitive to platinum. In athymic mice, the growth of tumors from inoculated SKOV3 cells was inhibited by the administration of platinum, whereas tumors from annexin A3-expressing SKOV3/Ann were resistant to platinum treatment. Interestingly, the intracellular platinum concentration and platinum-DNA binding are significantly lower in annexin A3-overexpressing cells than those in parental cells. The lower cisplatin concentration was also accompanied by reduced induction of p53, which could be restored by downregulation of annexin A3. These results indicate that increased expression of annexin A3 is a mechanism of platinum resistance in ovarian cancer. It seems to act by preventing uptake or accumulation of platinum in cells. Therefore, it is conceivable that annexin A3 could be a target for therapeutic intervention and may also serve as a biomarker for drug resistance in ovarian cancer patients.


Alu insertion polymorphisms in Native Americans and related Asian populations.
Alu insertions provide useful markers for the study of inter-population affinities and historical processes, but data on these systems are not numerous in Native Americans and related populations. The study aimed to answer the following questions: (a) do the population relationships found agree with ethnic, historical and geographical data? and (b) what can heterozygote levels and associated results inform us about the events that led to the colonization of the New World? Twelve Alu insertion polymorphisms were studied in 330 individuals belonging to South American Native, Siberian and Mongolian populations. These data were integrated with those from 526 persons, to ascertain the relationships between Asian, Northern Arctic and Amerindian populations. A decreasing trend concerning heterozygosities and amount of gene flow was observed in the three sets, in the order indicated above. Most results indicated the validity of these subdivisions. However, no clear structure could be observed within South American Natives, indicating the importance of dispersive (genetic drift, founder effects) factors in their differentiation. The answers to the questions are: (a) yes; and (b) an initial moderate bottleneck, intensified by more recent historical events (isolation and inbreeding), can explain the current Amerindian pattern of diversity.


Toward a Differential Diagnosis of Hidden Hearing Loss in Humans.
Recent work suggests that hair cells are not the most vulnerable elements in the inner ear; rather, it is the synapses between hair cells and cochlear nerve terminals that degenerate first in the aging or noise-exposed ear. This primary neural degeneration does not affect hearing thresholds, but likely contributes to problems understanding speech in difficult listening environments, and may be important in the generation of tinnitus and/or hyperacusis. To look for signs of cochlear synaptopathy in humans, we recruited college students and divided them into low-risk and high-risk groups based on self-report of noise exposure and use of hearing protection. Cochlear function was assessed by otoacoustic emissions and click-evoked electrocochleography; hearing was assessed by behavioral audiometry and word recognition with or without noise or time compression and reverberation. Both groups had normal thresholds at standard audiometric frequencies, however, the high-risk group showed significant threshold elevation at high frequencies (10-16 kHz), consistent with early stages of noise damage. Electrocochleography showed a significant difference in the ratio between the waveform peaks generated by hair cells (Summating Potential; SP) vs. cochlear neurons (Action Potential; AP), i.e. the SP/AP ratio, consistent with selective neural loss. The high-risk group also showed significantly poorer performance on word recognition in noise or with time compression and reverberation, and reported heightened reactions to sound consistent with hyperacusis. These results suggest that the SP/AP ratio may be useful in the diagnosis of "hidden hearing loss" and that, as suggested by animal models, the noise-induced loss of cochlear nerve synapses leads to deficits in hearing abilities in difficult listening situations, despite the presence of normal thresholds at standard audiometric frequencies.


Dexamethasone Does Not Inhibit Treadmill Training-Induced Angiogenesis in Myocardium: Role of MicroRNA-126 Pathway.
Dexamethasone (DEX) has important anti-inflammatory activities; however, it induces hypertension and skeletal muscle microcirculation rarefaction. Nevertheless, nothing is known about DEX outcomes on cardiac microcirculation. By contrast, exercise training prevents skeletal and cardiac microvessel loss because of microRNA expression and a better balance between their related angiogenic and apoptotic proteins in spontaneously hypertensive rats. The purpose of this study was to investigate whether DEX and/or exercise training could induce microRNA alterations leading to cardiac angiogenesis or microvascular rarefaction. Animals performed 8 weeks of exercise training and were treated with DEX (50 μg/kg per day, subcutaneously) for 14 days. Cardiovascular parameters were measured, and the left ventricle muscle was collected for analyses. DEX treatment increased arterial pressure and did not cause cardiac microcirculation rarefaction. Treadmill training prevented the DEX-induced increase in arterial pressure. In addition, training, regardless of DEX treatment, increased microRNA-126 expression, phospho-protein kinase B/protein kinase B, and endothelial nitric oxide synthase levels associated with cardiac angiogenesis. In conclusion, this study suggests, for the first time, that treadmill training induces myocardial angiogenesis because of angiogenic pathway improvement associated with an increase in microRNA-126. Furthermore, DEX, per se, did not cause capillary density alterations and did not attenuate cardiac angiogenesis induced by training.


Marine environment pollution: The contribution of mass spectrometry to the study of seawater.
The study of marine pollution has been traditionally addressed to persistent chemicals, generally known as priority pollutants; a current trend in environmental analysis is a shift toward "emerging pollutants," defined as newly identified or previously unrecognized contaminants. The present review is focused on the peculiar contribution of mass spectrometry (MS) to the study of pollutants in the seawater compartment. The work is organized in five paragraphs where the most relevant groups of pollutants, both "classical" and "emerging," are presented and discussed, highlighting the relative data obtained by the means of different MS techniques. The hyphenation of MS and separative techniques, together with the development of different ion sources, makes MS and tandem MS the analytical tool of choice for the determination of trace organic contaminants in seawater. © 2016 Wiley Periodicals, Inc. Mass Spec Rev 37:492-512, 2018.


Excess female child mortality in the developing world during the 1970s and 1980s.
"How did...excess female child mortality evolve from the 1970s to the 1980s, during a period when mortality declined significantly? Is there a relationship between the intensity of the phenomenon and levels of mortality or certain social development indicators? These are some of the questions which the article discusses on the basis of reliable and comparable data taken from approximately 60 [developing] countries."


SL2MF: Predicting Synthetic Lethality in Human Cancers via Logistic Matrix Factorization.
Synthetic lethality (SL) is a promising concept for novel discovery of anti-cancer drug targets. However, wet-lab experiments for detecting SLs are faced with various challenges, such as high cost, low consistency across platforms, or cell lines. Therefore, computational prediction methods are needed to address these issues. This paper proposes a novel SL prediction method, named SL2 MF, which employs logistic matrix factorization to learn latent representations of genes from the observed SL data. The probability that two genes are likely to form SL is modeled by the linear combination of gene latent vectors. As known SL pairs are more trustworthy than unknown pairs, we design importance weighting schemes to assign higher importance weights for known SL pairs and lower importance weights for unknown pairs in SL2 MF. Moreover, we also incorporate biological knowledge about genes from protein-protein interaction (PPI) data and Gene Ontology (GO). In particular, we calculate the similarity between genes based on their GO annotations and topological properties in the PPI network. Extensive experiments on the SL interaction data from SynLethDB database have been conducted to demonstrate the effectiveness of SL2 MF.


GenClust: a genetic algorithm for clustering gene expression data.
Clustering is a key step in the analysis of gene expression data, and in fact, many classical clustering algorithms are used, or more innovative ones have been designed and validated for the task. Despite the widespread use of artificial intelligence techniques in bioinformatics and, more generally, data analysis, there are very few clustering algorithms based on the genetic paradigm, yet that paradigm has great potential in finding good heuristic solutions to a difficult optimization problem such as clustering. GenClust is a new genetic algorithm for clustering gene expression data. It has two key features: (a) a novel coding of the search space that is simple, compact and easy to update; (b) it can be used naturally in conjunction with data driven internal validation methods. We have experimented with the FOM methodology, specifically conceived for validating clusters of gene expression data. The validity of GenClust has been assessed experimentally on real data sets, both with the use of validation measures and in comparison with other algorithms, i.e., Average Link, Cast, Click and K-means. Experiments show that none of the algorithms we have used is markedly superior to the others across data sets and validation measures; i.e., in many cases the observed differences between the worst and best performing algorithm may be statistically insignificant and they could be considered equivalent. However, there are cases in which an algorithm may be better than others and therefore worthwhile. In particular, experiments for GenClust show that, although simple in its data representation, it converges very rapidly to a local optimum and that its ability to identify meaningful clusters is comparable, and sometimes superior, to that of more sophisticated algorithms. In addition, it is well suited for use in conjunction with data driven internal validation measures and, in particular, the FOM methodology.


Sub-lethal effects of a glyphosate-based commercial formulation and adjuvants on juvenile oysters (Crassostrea gigas) exposed for 35days.
Glyphosate-based herbicides include active matter and adjuvants (e.g. polyethoxylated tallow amines, POEAs). In addition to a previous investigation on the effect of glyphosate on oysters, the aim of the present study was to investigate the effects of sub-chronic exposures (35days) to three concentrations (0.1, 1 and 100μgL-1) of Roundup Express® (REX) and POEAs on oysters belonging to the same age group. Low mortality rates were calculated, and only few significant differences (i.e. shell length) between exposure conditions were observed at a given date. However, when comparing the biomarker's temporal variations, some different patterns (e.g. condition index, reproduction, parameters of oxidative stress) were observed depending on the molecules and concentrations. These results suggest that a longer exposure to an environmental concentration (0.1μgL-1) of REX and POEAs could induce harmful effects on oysters.


Gut Microbiota and Host Metabolism: What Relationship.
A large number of genomic studies have reported associations between the gut microbiota composition and metabolic diseases such as obesity or type 2 diabetes. This led to the widespread idea that a causal relationship could exist between intestinal microbiota and metabolic diseases. At odds with this idea, some compelling studies reported that global changes in microbiota composition have no effect on the host metabolism in obese mice or humans. However, specific bacteria are able to confer host metabolic benefits, such as Akkermansia muciniphila or Prevotella copri, when they are given by gavage in obese mice. A crucial link by which gut bacteria communicate with the host mucosa is based on metabolites or low-molecular-weight compounds. Among them, short-chain fatty acids produced from the fermentation of dietary fibers initiate beneficial effects on the host metabolism via the activation of intestinal gluconeogenesis (a mucosal function exerting antidiabetic and antiobesity effects through the activation of gut-brain neural circuits). However, fermentation of short-chain fatty acids is a function that is widespread among the main bacterial phyla and thus weakly depends on microbiota composition. Therefore, even if some bacteria may confer on the host metabolic benefits, the causal role of microbiota in metabolic diseases is not established.


Suicide outside of prison settings among males under investigation for sex offenses in Ireland during 1990 to 1999.
Thirty-two cases of suicide outside prison were identified among 7008 Irish men under investigation for sexual offenses between 1990 and 1999. Previously this risk category has not been identified. Risk ratios of 1/1644 for those accused of offenses against adults, and 1/24 for those accused of offending against minors, respectively, were estimated based on the conservative estimates found here. The increase in the base rate of suicide in Ireland during the study period is an insufficient explanation. The frequency is comparable to prison suicides for the period, and the population of risk may overlap. The incidence increases over the study period. It outpaces increases in prosecutions and may reflect responses to the changing social environment of these investigations. These men use community psychiatric services that may need to become aware of the increased risk of suicide they pose.


To Those Who Have, More Will Be Given? Effects of an Instructional Time Reform on Gender Disparities in STEM Subjects, Stress, and Health.
Educational reformers all around the globe are continuously searching for ways to make schools more effective and efficient. In Germany, this movement has led to reforms that reduced overall school time of high track secondary schools from 9 to 8 years, which was compensated for by increasing average instruction time per week in lower secondary school (Grades 5-10). Based on prior research, we assumed that this reform might increase gender disparities in STEM-related outcomes, stress, and health because it required students to learn similar content in less amount of time. Therefore, we investigated how the school time reform affected gender disparities at the end of upper secondary school between 2011 and 2013. Specifically, we considered representative data of the last two cohorts who completed lower secondary school before the reform (N = 2,405) and the first two cohorts after the reform (N = 2,413) from the National Educational Panel Study. Potential differences in gender disparities were investigated for upper secondary school outcomes of subject-specific standardized test performance, self-concept, and interest in mathematics, biology and physics, as well as outcomes of school-related stress and health. Overall, we found substantial disparities between girls and boys, which seemed to change little after the reform. Exceptions were the statistically significant gender × reform interactions for one stress dimension (Overload) and two health dimensions (Overburdening and Achievement-related fear) which increased for both boys and girls, but more strongly for girls.


Experimental Study on Rebar Corrosion Using the Galvanic Sensor Combined with the Electronic Resistance Technique.
In this paper, a new kind of carbon steel (CS) and stainless steel (SS) galvanic sensor system was developed for the study of rebar corrosion in different pore solution conditions. Through the special design of the CS and SS electronic coupons, the electronic resistance (ER) method and zero resistance ammeter (ZRA) technique were used simultaneously for the measurement of both the galvanic current and the corrosion depth. The corrosion processes in different solution conditions were also studied by linear polarization resistance (LPR) and the measurements of polarization curves. The test result shows that the galvanic current noise can provide detailed information of the corrosion processes. When localized corrosion occurs, the corrosion rate measured by the ER method is lower than the real corrosion rate. However, the value measured by the LPR method is higher than the real corrosion rate. The galvanic current and the corrosion current measured by the LPR method shows linear correlation in chloride-containing saturated Ca(OH)₂ solution. The relationship between the corrosion current differences measured by the CS electronic coupons and the galvanic current between the CS and SS electronic coupons can also be used to evaluate the localized corrosion in reinforced concrete.


Fatal and non-fatal injuries from vessels under air pressure in construction.
Using a surveillance system that captures data on construction workers treated in an urban emergency department, we identified a series of injuries caused by vessels and tools under air pressure. We describe those six cases, as well as similar cases found in the Census of Fatal Occupational Injuries; we also review data from the National Surveillance for Traumatic Occupational Fatalities database and data from the Bureau of Labor Statistics. Among the injuries and deaths for which we had good case descriptions, the majority would have been prevented by adherence to existing Occupational Safety and Health Administration standards in the construction industry.


Agmatine Alleviates Cisplatin-Induced Ototoxicity by Activating PI3K/AKT Signaling Pathway.
Cisplatin-induced ototoxicity can be partially attributed to excessive reactive oxygen species (ROS) production, and agmatine is well-known for the activation of the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) pathway to inhibit ROS production. Whether agmatine could be used to alleviate cisplatin-induced ototoxicity is investigated. Cisplatin-exposed House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and cochlear explants showed increased ROS production detected by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining and decreased cell viability detected by Cell Counting Kit-8 (CCK-8) or Myosin 7a staining, which could be reversed by the agmatine pretreatment. Cisplatin intraperitoneally injected C57BL/6 mice demonstrated damaged auditory function as indicated by distortion products otoacoustic emissions (DPOAEs) and auditory brainstem response (ABR) assays, and trans-tympanically administrated agmatine in the left ears could partly prevent the auditory function loss. Mechanistically, downregulated B-cell lymphoma 2 (Bcl-2) expression, upregulated Bcl2-associated x (Bax) expression, and diminished p-PI3K and p-AKT expression were detected in cisplatin-exposed HEI-OC1 cells and cochlear explants, which could be prevented by the pretreatment with agmatine. Our investigation demonstrates that agmatine pretreatment could alleviate cisplatin-induced ototoxicity with the activation of PI3K/AKT signaling pathway.


Passivating ZnO Surface States by C60 Pyrrolidine Tris-Acid for Hybrid Solar Cells Based on Poly(3-hexylthiophene)/ZnO Nanorod Arrays.
Construction of ordered electron acceptors is a feasible way to solve the issue of phase separation in polymer solar cells by using vertically-aligned ZnO nanorod arrays (NRAs). However, the inert charge transfer between conducting polymer and ZnO limits the performance enhancement of this type of hybrid solar cells. In this work, a fullerene derivative named C60 pyrrolidine tris-acid is used to modify the interface of ZnO/poly(3-hexylthiophene) (P3HT). Results indicate that the C60 modification passivates the surface defects of ZnO and improves its intrinsic fluorescence. The quenching efficiency of P3HT photoluminescence is enhanced upon C60 functionalization, suggesting a more efficient charge transfer occurs across the modified P3HT/ZnO interface. Furthermore, the fullerene modified hybrid solar cell based on P3HT/ZnO NRAs displays substantially-enhanced performance as compared to the unmodified one and the devices with other modifiers, which is contributed to retarded recombination and enhanced exciton separation as evidenced by electrochemical impedance spectra. Therefore, fullerene passivation is a promising method to ameliorate the connection between conjugated polymers and metal oxides, and is applicable in diverse areas, such as solar cells, transistors, and light-emitting dioxides.