Aerobiological Stabilities of Different Species of Gram-Negative Bacteria, Including Well-Known Biothreat Simulants, in Single-Cell Particles and Cell Clusters of Different Compositions.
The ability to perform controlled experiments with bioaerosols is a fundamental enabler of many bioaerosol research disciplines. A practical alternative to using hazardous biothreat agents, e.g., for detection equipment development and testing, involves using appropriate model organisms (simulants). Several species of Gram-negative bacteria have been used or proposed as biothreat simulants. However, the appropriateness of different bacterial genera, species, and strains as simulants is still debated. Here, we report aerobiological stability characteristics of four species of Gram-negative bacteria (Pantoea agglomerans, Serratia marcescens, Escherichia coli, and Xanthomonas arboricola) in single-cell particles and cell clusters produced using four spray liquids (H2O, phosphate-buffered saline[PBS], spent culture medium[SCM], and a SCM-PBS mixture). E. coli showed higher stability in cell clusters from all spray liquids than the other species, but it showed similar or lower stability in single-cell particles. The overall stability was higher in cell clusters than in single-cell particles. The highest overall stability was observed for bioaerosols produced using SCM-containing spray liquids. A key finding was the observation that stability differences caused by particle size or compositional changes frequently followed species-specific patterns. The results highlight how even moderate changes to one experimental parameter, e.g., bacterial species, spray liquid, or particle size, can strongly affect the aerobiological stability of Gram-negative bacteria. Taken together, the results highlight the importance of careful and informed selection of Gram-negative bacterial biothreat simulants and also the accompanying particle size and composition. The outcome of this work contributes to improved selection of simulants, spray liquids, and particle size for use in bioaerosol research.IMPORTANCE The outcome of this work contributes to improved selection of simulants, spray liquids, and particle size for use in bioaerosol research. Taken together, the results highlight the importance of careful and informed selection of Gram-negative bacterial biothreat simulants and also the accompanying particle size and composition. The results highlight how even moderate changes to one experimental parameter, e.g., bacterial species, spray liquid, or particle size, can strongly affect the aerobiological stability of Gram-negative bacteria. A key finding was the observation that stability differences caused by particle size or compositional changes frequently followed species-specific patterns.


Diffusion tensor imaging to aid subgenual cingulum target selection for deep brain stimulation in depression.
The most investigated target for deep brain stimulation in depression is the subgenual cingulate gyrus (Cg25) which has been shown to be a critical hub for signalling in the condition. Diffusion tensor imaging (DTI) is a form of MR sequence that can visualise white matter connections and potentially aid target selection. To assess whether targets selected using DTI to find the area of maximal tract crossover (maximal isotropy) underlying the subgenual cingulum differ significantly in location from those selected using standard T(2) sequences. Fifty-nine non-depressed adult volunteers underwent MR imaging using T(1), T(2) and DTI sequences of the brain. Each patient had targets selected for both hemispheres using both T(2) and DTI sequences. The significance of the differences in coordinates in all three dimensions was tested using the paired t test. There was a significant difference in the mediolateral (x) and dorsoventral (z) coordinates of DTI targets when compared with T(2) targets (p < 0.001). Targets within Cg25 selected using DTI are significantly different in location from those selected using T(2) sequences and have the potential to enhance treatment outcome by reducing the impact of interindividual variability.


Sub-projection-noise sensitivity in broadband atomic magnetometry.
We demonstrate sub-projection-noise sensitivity of a broadband atomic magnetometer using quantum nondemolition spin measurements. A cold, dipole-trapped sample of rubidium atoms provides a long-lived spin system in a nonmagnetic environment, and is probed nondestructively by paramagnetic Faraday rotation. The calibration procedure employs as known reference state, the maximum-entropy or "thermal" spin state, and quantitative imaging-based atom counting to identify electronic, quantum, and technical noise in both the probe and spin system. The measurement achieves a sensitivity 1.6 dB (2.8 dB) better than projection-noise (thermal state quantum noise) and will enable squeezing-enhanced broadband magnetometry.


Role of PEPT2 in peptide/mimetic trafficking at the blood-cerebrospinal fluid barrier: studies in rat choroid plexus epithelial cells in primary culture.
Recent studies have established the functional and molecular presence of a high-affinity peptide transporter, PEPT2, in whole tissue rat choroid plexus. However, the precise membrane location and directionality of PEPT2-mediated transport is uncertain at present. In this study, we examined the transport kinetics of a model dipeptide, glycylsarcosine (GlySar), along with the protein expression of PEPT2 using primary cell cultures of choroidal epithelium from neonatal rats. GlySar accumulation and transepithelial transport were 3 to 4 times higher when introduced from the apical as opposed to the basal side of the monolayers. GlySar apical uptake was also stimulated by an inwardly directed proton gradient. The uptake of GlySar was inhibited by di/tripeptides, carnosine, and alpha-amino cephalosporins but was unaffected by amino acids, cephalosporins lacking an alpha-amino group, and organic anions and cations. The Michaelis constant (K(m)) of GlySar was 59.6 microM for apical uptake and 1.4 mM for basal uptake; this is consistent with the high-affinity properties of PEPT2 at the apical membrane. Immunoblot analyses and immunofluorescent confocal microscopy demonstrated the presence of PEPT2, but not PEPT1, in rat choroid plexus epithelial cells. Moreover, PEPT2 was present in the apical and subapical regions of the cell but was absent in the basolateral membrane. These findings demonstrate, for the first time, that PEPT2 protein is present at the apical membrane of choroidal epithelial cells and that it is functionally active at this membrane surface. The results suggest that PEPT2 may have a role in the efflux of peptides and/or mimetics from cerebrospinal fluid to the blood.


Reduced cerebral vasomotor reactivity as an indicator of postoperative confusion.
Surgical intervention in elderly patients carries a high risk. A frequent problem with surgery in these patients is the occurrence of a temporary confusional state, which increases both the risk of postoperative complications and the need for intensive care. We hypothesised that, in part, temporary confusional state results from cerebral hypoxia occurring in response to blood pressure fluctuations during surgery. To assess whether disruption of autoregulation of cerebral blood vessels plays a role in temporary confusional state, we studied 31 patients over 55 years of age, using the Doppler-carbon dioxide test. We determined whether vasomotor reactivity could be used diagnostically to identify those patients most likely to experience temporary confusional state. Blood flow velocity in the middle cerebral artery was detected using Doppler ultrasound, and hypercapnia was induced by breathing carbon dioxide until an end-tidal concentration of 8.0% by volume was reached. Vasomotor reactivity was calculated on the basis of the changes in blood flow velocity in response to the increase in carbon dioxide. Temporary confusional state was assessed using the Syndrome Short Test (Syndrom-Kurztest). We found that resting blood flow velocity was inversely related to age (p < 0.05). In addition, there was a significant inverse correlation between vasomotor reactivity and temporary confusional state (p < 0.05). These data indicate that vasomotor reactivity, as measured by the Doppler-carbon dioxide test, is a reliable tool to identify patients at risk for postoperative psychological disturbances.


Immunotherapy of asthma using CpG oligodeoxynucleotides.
Asthma and other atopic disorders have increased in prevalence and severity over the past three decades. Reduced risk of atopic disease associated with early life exposure to infections and microbes has raised the possibility that pathogen-associated molecular patterns (PAMPs) may confer protection against allergic disorders, a concept that has been named the "Hygiene Hypothesis". This relationship is most likely mediated through the induction of specific patterns of anti-atopic immune responses that follow engagement of innate immune mechanisms. Bacterial DNA is one such immunostimulatory microbe-associated ligand, whose properties can be mimicked by oligodeoxynucleotides (ODN) containing unmethylated cytosine-guanine dinucleotides in specific base sequences (CpG motifs), motifs characteristic of prokaryotic DNA that have been suppressed in eukaryotic DNA. Based initially on observations that CpG ODN induced Th1-type patterns of immune responses, we proposed that CpG ODN might represent a novel therapeutic strategy for the prevention and treatment of atopic disorders. Current understanding suggests multiple mechanisms of action of CpG ODN, but our initial hypothesis has been supported by extensive studies demonstrating, in animal models, efficacy in both incipient and established atopic asthma. These preclinical studies are now being translated into clinical trials exploring this new approach to immunotherapy for atopic disease.


A low-power photonic quantization approach using OFDM subcarrier spectral shifts.
Photonic analog-to-digital conversion and optical quantization are demonstrated, based on the spectral shifts of orthogonal frequency division multiplexing subcarriers and a frequency-packed arrayed waveguide grating. The system is extremely low-energy consuming since the spectral shifts are small and generated by cross-phase modulation, using a linear-slope high-speed and low-jitter pulse train generated by a mode locked laser diode. The feasibility of a 2, 3 and 4-bit optical quantization scheme is demonstrated.


2,2'-Fluorine mono-carbonyl curcumin induce reactive oxygen species-Mediated apoptosis in Human lung cancer NCI-H460 cells.
In this paper, we synthesized three fluorine-substituted mono-carbonyl curcumin analogs and evaluated their cytotoxicity against several cancer cells by the MTT assay. The results exhibited that all the three compounds were more active than the leading curcumin. Especially, 2,2'-F mono-carbonyl curcumin, 1a, surfaced as an important lead compound displaying almost 4-fold cytotoxicity relative to curcumin. More importantly, 1a was more stable in (RPMI)-1640 medium and more massive uptake than curcumin, which may be relationship to their cytotoxicity, apoptotic acitivity and reactive oxygen species generation. And then, the generation of reactive oxygen species can disrupt the intracellular redox balance, induce lipid peroxidation, cause the collapse of the mitochondrial membrane potential and ultimately lead to apoptosis. The results not only suggest that 2,2'-F mono-carbonyl curcumin (1a) may cause cancer cells apoptosis through reactive oxygen species-Mediated pathway, but also gives us an important information for design of mono-carbonyl curcumin analog.


Modulation of hypericin photodynamic therapy by pretreatment with 12 various inhibitors of arachidonic acid metabolism in colon adenocarcinoma HT-29 cells.
One proposal to increase the efficiency of photodynamic therapy (PDT) is to accompany photosensitization with other treatment modalities, including modulation of arachidonic acid (AA) metabolism. The aim of this study was to evaluate the effectiveness of a combined modality approach employing 48 and 24 h pretreatment with various inhibitors of lipoxygenase (LOX; nordihydroguaiaretic acid, esculetin, AA-861, MK-886 and baicalein), cyclooxygenase (COX; diclofenac, flurbiprofen, ibuprofen, indomethacin, SC-560 and rofecoxib) and cytochrome P450-monooxygenase (proadifen) pathways, followed by hypericin-mediated PDT. Cytokinetic parameters like MTT assay, adherent and floating cell numbers, viability and cell cycle distribution analysis were examined 24 h after hypericin activation. Pretreatment of human colon cancer cells HT-29 prior to PDT with 5-LOX inhibitor MK-886 as well as 5, 12-LOX and 12-LOX inhibitors (esculetin and baicalein, respectively) resulted in significant and dose-dependent effects on all parameters tested. Pretreatment with diclofenac, flurbiprofen, ibuprofen and indomethacin, the nonspecific COX inhibitors, promoted hypericin-mediated PDT, but these effects were probably COX-independent. In contrast, application of SC-560 and rofecoxib, specific inhibitors of COX-1 and COX-2, respectively, attenuated PDT. Inhibition of P450 monooxygenase with proadifen implied also the significance of this metabolic pathway in cell survival and cell resistance to hypericin photocytotoxicity. In conclusion, our results testify that application of diverse inhibitors of AA metabolism may have different consequences on cellular response to hypericin-mediated PDT and that some of them could be considered for potentiation of PDT.


Is there silicon in flowers and what does it tell us?
The emergence of flowers marked an important development in plant evolution. Flowers in many species evolved to attract animal pollinators to increase fertilisation chances. In leaves, silicon (Si) discourages herbivores, for example by wearing down mouthparts. Flowers are essentially modified leaves and hence may also have the capacity to accumulate Si. If Si in flowers discourages animal visitors as it does in leaves, Si accumulation may be disadvantageous for pollination. Whether flowers accumulate Si, and what the implications may be, was not known for many species. We analysed leaves and flowers of different taxa, separated into their different anatomical parts. Flowers mostly have low Si concentrations in all parts (mean ± SE of BSi in mg g-1 was 0.22 ± 0.04 in petals, 0.59 ± 0.24 in sepals, 0.14 ± 0.03 in stamens, 0.15 ± 0.04 in styles and stigmas and 0.37 ± 0.19 in ovaries for a subset of 56 species). In most cases, less Si was accumulated in flowers than in leaves (mean ± SE of BSi in mg g-1 was 1.51 ± 0.55 in whole flowers vs. 2.97 ± 0.57 in leaves in 104 species) though intriguing exceptions are found, with some species accumulating more Si in flowers than leaves. The large variation in concentration among flowers across the taxa examined, with a particularly high concentration in grass inflorescences, tantalisingly suggests differences in the use of Si for flowers across plant groups. We conclude that the study of the functions of Si for flowers warrants more attention, with pollination strategy a potential contributing factor.


Low-expression of TMEM100 is associated with poor prognosis in non-small-cell lung cancer.
Transmembrane protein 100 (TMEM100) was first identified as a transcript from the mouse genome. Recent studies have demonstrated that TMEM100 is involved in hepatocellular carcinoma (HCC) malignancy. However, the distribution and clinical significance of TMEM100 in non-small-cell lung carcinoma (NSCLC) remains poorly understood. This study aims to explore the significance of TMEM100 expression in NSCLC. We found that TMEM100 expression was significantly reduced in NSCLC tissues when compared with that in adjacent normal lung tissues (P<0.001). Kaplan-Meier survival analysis showed that overall survival of patients with lower expressions of TMEM100 was significantly shorter (n=152, P<0.05). In addition, TMEM100 overexpression in NSCLC cell lines inhibited cell proliferation in vitro and in vivo. Transwell migration and invasion assay showed that TMEM100 significantly suppressed the migration and invasion of NSCLC cell lines. In contrast, knocking down TMEM100 promoted NSCLC proliferation and migration. Finally, we found that TMEM100 worked as a cancer suppressor gene mainly by inhibiting the TNF signaling pathway. In conclusion, TMEM100 acted as a tumor suppressor in NSCLC and may prove to be a potential prognostic biomarker and therapeutic target for NSCLC.


Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial.
Most patients with irritable bowel syndrome (IBS) are managed in primary care. When first-line therapies for IBS are ineffective, the UK National Institute for Health and Care Excellence guideline suggests considering low- dose tricyclic antidepressants as second-line treatment, but their effectiveness in primary care is unknown, and they are infrequently prescribed in this setting. This randomised, double-blind, placebo-controlled trial (Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment [ATLANTIS]) was conducted at 55 general practices in England. Eligible participants were aged 18 years or older, with Rome IV IBS of any subtype, and ongoing symptoms (IBS Severity Scoring System [IBS-SSS] score ≥75 points) despite dietary changes and first-line therapies, a normal full blood count and C-reactive protein, negative coeliac serology, and no evidence of suicidal ideation. Participants were randomly assigned (1:1) to low-dose oral amitriptyline (10 mg once daily) or placebo for 6 months, with dose titration over 3 weeks (up to 30 mg once daily), according to symptoms and tolerability. Participants, their general practitioners, investigators, and the analysis team were all masked to allocation throughout the trial. The primary outcome was the IBS-SSS score at 6 months. Effectiveness analyses were according to intention-to-treat; safety analyses were on all participants who took at least one dose of the trial medication. This trial is registered with the ISRCTN Registry (ISRCTN48075063) and is closed to new participants. Between Oct 18, 2019, and April 11, 2022, 463 participants (mean age 48·5 years [SD 16·1], 315 [68%] female to 148 [32%] male) were randomly allocated to receive low-dose amitriptyline (232) or placebo (231). Intention-to-treat analysis of the primary outcome showed a significant difference in favour of low-dose amitriptyline in IBS-SSS score between groups at 6 months (-27·0, 95% CI -46·9 to -7·10; p=0·0079). 46 (20%) participants discontinued low-dose amitriptyline (30 [13%] due to adverse events), and 59 (26%) discontinued placebo (20 [9%] due to adverse events) before 6 months. There were five serious adverse reactions (two in the amitriptyline group and three in the placebo group), and five serious adverse events unrelated to trial medication. To our knowledge, this is the largest trial of a tricyclic antidepressant in IBS ever conducted. Titrated low-dose amitriptyline was superior to placebo as a second-line treatment for IBS in primary care across multiple outcomes, and was safe and well tolerated. General practitioners should offer low-dose amitriptyline to patients with IBS whose symptoms do not improve with first-line therapies, with appropriate support to guide patient-led dose titration, such as the self-titration document developed for this trial. National Institute for Health and Care Research Health Technology Assessment Programme (grant reference 16/162/01).


Flow cytometric recognition of clastogen induced chromatin damage in G0/G1 lymphocytes by non-stoichiometric Hoechst fluorochrome binding.
Changes in chromatin structure were induced in human peripheral blood lymphocytes. Resting G0/G1 cells were exposed to either X-rays, mitomycin C, or bleomycin and stimulated with PHA. Exposure to such agents provokes an increase in the non-cycling cell fraction; and a distinctive, non-cycling G-/G1 subpopulation appears which is characterized by a 23% reduced Hoechst fluorescence intensity. This novel subpopulation was found as early as 24 h after PHA stimulation; it was still present in 72 h cultures. Bromodeoxyuridine (BrdUrd/Hoechst 33258-ethidium bromide (EB) flow cytometric analysis revealed increments of this subpopulation from 2% of the non-cycling cell fraction in the control culture to 29% (X-rays), 15% (mitomycin C), and 24% (bleomycin) after clastogen exposure. In the presence of the ligase inhibitor 3-aminobenzamide, this aberrant cell population increased significantly after X-ray treatment. With the aid of a viable BrdUrd/Hoechst staining assay, the newly identified non-cycling subpopulation with decreased Hoechst 33258 binding was identified as a distinctive signal cluster. Other than the regular non-cycling and cycling cell fractions, this subpopulation with non-stoichiometric Hoechst dye binding showed progressive uptake of ethidium bromide; however, by such criteria 44% of the subpopulation was still viable. It is concluded that the clastogen induced subpopulation of non-cycling cells represents damaged cells with altered dye binding properties.


[Street prostitution and drug addiction].
Street-based prostitution accounts for 10% of the prostitution activity in Denmark, mainly involving female drug addicts. We studied a group of women with a common history of substance abuse and their comparative psychosocial characteristics, correlated with whether they had previously been a prostitute or not. Their psychic symptoms were evaluated and compared with those of controls. 27 females receiving maintenance treatment for substance abuse completed a questionnaire dealing with their social background, substance abuse profile, and history of sexual abuse and prostitution, as well as their current health status, including SCL-90. The scores were compared to those of a control group of an age- and gender-matched Danish standard population. Neglect in childhood and adulthood corresponded to international findings. 14 of the women had previous sex-trading experience, and early use of heroin and cocaine was a predictor for starting a career in prostitution. The SCL-90 scores for the dimensions of somatization and depression were significantly higher for drug-abusing women in general than in the control group. The scores of drug-abusing former prostitutes were similarly significantly higher on most of the dimensions except the hostility dimension when compared to those of drug-abusing women who had never been involved in prostitution. Rape and domestic violence were characteristic phenomena among drug-abusing prostitutes (p < or = 0.05). Victimization during childhood and adulthood constitutes a serious risk for generating social vulnerability through drug addiction and prostitution. Various psychosocial stress factors among street-based prostitutes indicate the need for broader psychiatric approaches in Danish drug addiction maintenance programmes.


Intraspecific phytochemical variation shapes community and population structure for specialist caterpillars.
Chemically mediated plant-herbivore interactions contribute to the diversity of terrestrial communities and the diversification of plants and insects. While our understanding of the processes affecting community structure and evolutionary diversification has grown, few studies have investigated how trait variation shapes genetic and species diversity simultaneously in a tropical ecosystem. We investigated secondary metabolite variation among subpopulations of a single plant species, Piper kelleyi (Piperaceae), using high-performance liquid chromatography (HPLC), to understand associations between plant phytochemistry and host-specialized caterpillars in the genus Eois (Geometridae: Larentiinae) and associated parasitoid wasps and flies. In addition, we used a genotyping-by-sequencing approach to examine the genetic structure of one abundant caterpillar species, Eois encina, in relation to host phytochemical variation. We found substantive concentration differences among three major secondary metabolites, and these differences in chemistry predicted caterpillar and parasitoid community structure among host plant populations. Furthermore, E. encina populations located at high elevations were genetically different from other populations. They fed on plants containing high concentrations of prenylated benzoic acid. Thus, phytochemistry potentially shapes caterpillar and wasp community composition and geographic variation in species interactions, both of which can contribute to diversification of plants and insects.


Burden of antimicrobial resistance in an era of decreasing susceptibility.
Antimicrobial resistance has become a global problem. Many pathogens are becoming multidrug-resistant with the attendant increased risk of failure of standard therapies and the under-recognised outcomes such as increased morbidity, mortality, length of hospitalization and costs of treatment. Areas covered: We undertook a review of the literature using standard search engines including PubMed, Google Scholar, Scopus and internet sources. Key search terms included antimicrobial resistance, antibiotic resistance, bacterial resistance, clinical outcomes, economic consequences, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Streptococcus pneumoniae and Staphylococcus aureus. Expert commentary: Antimicrobial resistance among the five-species presented demonstrates a major, and increasing, deleterious impact seen in each of the key outcomes measured. These negative changes, at a personal, health system and Societal levels, further emphasise the growing problem of increasing antimicrobial resistance at a global level and the vital need for new antimicrobials.


Joint temporal trends in river thermal and hydrological conditions can threaten the downstream migration of the critically endangered European eel.
Climate change is modifying the hydrological and thermal regimes of rivers worldwide, threatening the triggering of organisms' key life-cycle processes. European eel (Anguilla anguilla) is a critically endangered fish species that migrates over several thousand kilometres between its rearing habitats in continental waters of Europe and North Africa and its spawning area in the Sargasso Sea. Downstream migration of adult eels occurs during periods of decreasing river water temperature associated with high discharge but changes in these environmental cues may affected eel migratory conditions. An innovative multivariate method was developed to analyse long-term datasets of daily water temperature, discharge and eel passage in two European rivers. Over the past 50 years, water temperature and discharge increased in both rivers during the downstream migration period from August to November. Silver eels preferentially migrated at temperatures between 10 and 20 °C combined with high discharge. Environmental changes have resulted in the migration of silver eels under warmer water temperatures. This example illustrates how the changes in environmental cues have led to a growing mismatch between the migratory conditions preferentially selected and those actually used, which may threaten the completion of the eel's life cycle and ultimately the persistence of this already critically endangered species.


The effects of volatile anesthetics on the relative amplitudes and latencies of spinal and muscle potentials evoked by transcranial magnetic stimulation.
The effects of halothane, enflurane, or isoflurane on motor-evoked potentials via transcranial magnetic stimulation were investigated in cats. Time and dose effects on muscle potentials and spinal potentials were determined by measuring relative changes in amplitudes and latencies. In 16 cats, muscle potentials and spinal potentials were evoked transcranially using magnetic stimulation. Potentials were recorded every 2 minutes for 10 minutes at end-tidal anesthetic concentrations of 0.25%, 0.5%, 0.75%, or 1.0%, and for 10 minutes after agents were removed. These anesthetics significantly attenuated the amplitude, but not the latency of muscle potentials. Effects were reversible and time and dose dependent. In contrast, these agents had little or no effect on amplitudes or latencies of spinal potentials. Monitoring intraoperative changes in spinal potentials may provide useful information regarding motor pathway assessment, because anesthetics have minimal effects on spinal potentials, whereas this is not so for muscle potentials.


How Effective the Mindfulness-Based Cognitive Behavioral Therapy on Quality of Life in Women With Menopause.
In woman's life menopause can cause psychological and somatic disturbances. Psychological and behavioural intervention is effective in reducing menopause-related symptoms. The present study was done to find effectiveness of mindfulness-based cognitive behavioural therapy (MBCT) on quality of life among menopausal women. The present study was double-blind randomized trial conducted among menopausal women at tertiary care hospital, Chennai, Tamil Nadu. The study was conducted among 50 women who had attained menopause. They were randomly divided into intervention (n = 25) and control (n = 25) groups. The MBCT was given once a week to intervention group over eight one-hour sessions and control group received no intervention. The data collection instruments included a demographic questionnaire, Kupperman's index, and menopause-related quality of life questionnaire, which were fulfilled by both groups before, immediately after, and 2 weeks after completion of intervention. Paired t-test was applied before intervention and at 10 weeks for both the groups. The difference between the scores before and after intervention i.e after 10 weeks in all the domains and total domain was significant in intervention group compared to control group. Mindfulness based approaches may improve severity of vasomotor and psychological symptoms of menopause, thus enhancing quality of life.


A novel mechanism involved in the coupling of mitochondrial biogenesis to oxidative phosphorylation.
Mitochondria are essential organelles that are central to a multitude of cellular processes, including oxidative phosphorylation (OXPHOS), which produces most of the ATP in animal cells. Thus it is important to understand not only the mechanisms and biogenesis of this energy production machinery but also how it is regulated in both physiological and pathological contexts. A recent study by Ostojić et al. [Cell Metabolism (2013) 18, 567-577] has uncovered a regulatory loop by which the biogenesis of a major enzyme of the OXPHOS pathway, the respiratory complex III, is coupled to the energy producing activity of the mitochondria.


Swelling of Graphene Oxide Membranes in Aqueous Solution: Characterization of Interlayer Spacing and Insight into Water Transport Mechanisms.
Graphene oxide (GO) has recently emerged as a promising 2D nanomaterial to make high-performance membranes for important applications. However, the aqueous-phase separation capability of a layer-stacked GO membrane can be significantly limited by its natural tendency to swell, that is, absorb water into the GO channel and form an enlarged interlayer spacing (d-spacing). In this study, the d-spacing of a GO membrane in an aqueous environment was experimentally characterized using an integrated quartz crystal microbalance with dissipation and ellipsometry. This method can accurately quantify a d-spacing in liquid and well beyond the typical measurement limit of ∼2 nm. Molecular simulations were conducted to fundamentally understand the structure and mobility of water in the GO channel, and a theoretical model was developed to predict the d-spacing. It was found that, as a dry GO membrane was soaked in water, it initially maintained a d-spacing of 0.76 nm, and water molecules in the GO channel formed a semiordered network with a density 30% higher than that of bulk water but 20% lower than that of the rhombus-shaped water network formed in a graphene channel. The corresponding mobility of water in the GO channel was much lower than in the graphene channel, where water exhibited almost the same mobility as in the bulk. As the GO membrane remained in water, its d-spacing increased and reached 6 to 7 nm at equilibrium. In comparison, the d-spacing of a GO membrane in NaCl and Na2SO4 solutions decreased as the ionic strength increased and was ∼2 nm at 100 mM.


A digital module for cardiac pacemaker assessment.
The accuracy of a digital pacemaker testing module incorporated into a digital recording electrocardiograph has been tested against two other methods of waveform recording. Measurements of rate (pulse interval), pulse width, pulse amplitude and ratio of trailing edge to the leading edge amplitude were found to be highly accurate. The pulse shapes were faithfully recorded. The practical clinical use of the method is discussed.


An automated screening test for antibodies to human immunodeficiency virus-1.
An automated pretransfusion testing system was applied to HIV antibody screening by a gelatin particle agglutination (HIV-PA) test. The test conditions for the test, such as diluent, plate shape, and incubation time, were applicable not only for the HIV-PA test but also for other routine tests, including those for hepatitis B surface antigen and HTLV-1 antibodies. After a 60-minute incubation, the plates were read automatically and then were assessed visually. Tests with seropositive samples obtained from hemophiliacs and an HIV enzyme immunoassay (EIA) familiarization panel showed that the automated HIV-PA test was more sensitive than the EIA and did not show a false-negative result. Of 11,300 blood donors, 44 were positive by the automated test, and 51 were positive by the EIA. None of the blood donors was confirmed to be seropositive. Using the automated test, a large number of samples could be screened in a relatively short time without a significant increase of nonspecific reactions.


Prolongation of the QT interval by ketanserin.
In hypertensive patients single doses of ketanserin 40 mg prolonged the corrected QT interval (QTc) for at least 8 hours, with a maximal increase of 35 ms (P less than 0.001, n = 6) after 2 hours. During chronic dosing (20 and 40 mg b.d.) the QTc was further prolonged, by 46 and 45 ms respectively. QTc prolongation after treatment with a mean dose of 73 mg/day for 7 weeks (n = 26) was significantly related to body weight (r = -0.58, P less than 0.01), and to the dose of ketanserin corrected for body weight (r = 0.63, P less than 0.01), but not to plasma concentrations of ketanserin, ketanserinol, potassium or calcium. High doses of ketanserin (mean dose 167 mg/day, n = 9) increased the QTc by 40 ms (P less than 0.001), with prolongation of up to 80 ms in individual patients. Treatment with ketanserin at doses proposed for clinical use (40-80 mg/day) may carry a risk of ventricular arrhythmias.


Spermatogenesis associated 22 is required for DNA repair and synapsis of homologous chromosomes in mouse germ cells.
Analysis of the N-ethyl-N-nitrosourea (ENU)-induced repro42 mutation previously identified spermatogenesis associated 22 (Spata22) as a gene required for meiotic progression and fertility in both male and female mice, but its specific contribution to the process was unclear. Here, we report on a novel, null allele of Spata22 (Spata22Gt ) and confirm its requirement for germ cell development. Similar to repro42 mutant mice, histological and mating analyses indicate that gametogenesis is profoundly affected in Spata22Gt/Gt males and females, resulting in infertility. Cytological examination confirms that germ cells do not progress beyond zygonema and meiotic arrest is linked to impairment of both synapsis and DNA repair. Analysis of SPATA22 distribution reveals that it localizes to foci associated with meiotic chromosomes during prophase I and that the number of foci peaks at zygonema; there are also more SPATA22 foci in oocytes than in spermatocytes. Furthermore, SPATA22 co-localizes with a number of proteins involved in meiotic recombination, including RAD51, DMC1, and MLH1, and is present until mid-pachynema, suggesting a role in resolution of recombination intermediates. In fact, SPATA22 co-localizes with MLH1 in more than 20% of foci at pachynema. Analysis of Spata22Gt/Gt meiocytes confirms that SPATA22 is required for localization of MEIOB but not RPA (two proteins known to interact with SPATA22), and immunoblotting corroborates that production of MEIOB is indeed decreased in the absence of SPATA22. Together, these data suggest that SPATA22 is required for both meiotic recombination and synapsis during meiosis in mice.


[Remifentanil--ultra-short acting opioid and its possible applications in anesthesiology].
Remifentanil is a new, ultra-short acting opioid, which may be applied in several branches of anaesthesia. Data concerning pharmacokinetics and pharmacodynamics as well as review of references regarding practical use, combining this drug with other anaesthetics agents and side effects are given. Particular attention is paid to the usefulness of remifentanil to provide good control of haemodynamics and stress response during surgical procedures. Remifentanil also seems to be very effective in the intensive care setting and for pain control during various medical procedures.


The role of the sodium cycle of energy coupling in the emergence and persistence of natural foci of modern cholera.
A hypothesis on the appearance and persistence of natural foci of cholera based on ecological and bioenergetic features of the process has been developed. The main causes of persistence and propagation of modern cholera are: 1) inability of various bacteria, including the genus Vibrio and many cyanobacterial species, to perform energy coupling, depending on external conditions, by means of two cycles (the proton and sodium cycles); induction of the sodium cycle of energy coupling increases the resistance of bacteria to various environmental factors, such as high concentrations of sodium, alkaline pH, and a high proton conductance of coupling membranes [1], and probably the virulence of the vibrios; 2) development of cyanobacteria in an aquatic environment enriched with Na+ accelerates alkalization of the medium and stimulates the development of the community of cyanobacteria with Vibrio cholerae, an autochthonous inhabitant of saline water bodies and marine shallow waters; 3) salinization of water bodies accelerates their blooming and enriches them with soluble organic matter, a substrate for vibrios inhabiting the biotope; 4) further propagation of cholera infection is related to eating heat-untreated hydrobionts from blooming water bodies [2].


Hidden variation in polyploid wheat drives local adaptation.
Wheat has been domesticated into a large number of agricultural environments and has the ability to adapt to diverse environments. To understand this process, we survey genotype, repeat content, and DNA methylation across a bread wheat landrace collection representing global genetic diversity. We identify independent variation in methylation, genotype, and transposon copy number. We show that these, so far unexploited, sources of variation have had a significant impact on the wheat genome and that ancestral methylation states become preferentially "hard coded" as single nucleotide polymorphisms (SNPs) via 5-methylcytosine deamination. These mechanisms also drive local adaption, impacting important traits such as heading date and salt tolerance. Methylation and transposon diversity could therefore be used alongside SNP-based markers for breeding.


Magnetization dynamics and its scattering mechanism in thin CoFeB films with interfacial anisotropy.
Studies of magnetization dynamics have incessantly facilitated the discovery of fundamentally novel physical phenomena, making steady headway in the development of magnetic and spintronics devices. The dynamics can be induced and detected electrically, offering new functionalities in advanced electronics at the nanoscale. However, its scattering mechanism is still disputed. Understanding the mechanism in thin films is especially important, because most spintronics devices are made from stacks of multilayers with nanometer thickness. The stacks are known to possess interfacial magnetic anisotropy, a central property for applications, whose influence on the dynamics remains unknown. Here, we investigate the impact of interfacial anisotropy by adopting CoFeB/MgO as a model system. Through systematic and complementary measurements of ferromagnetic resonance (FMR) on a series of thin films, we identify narrower FMR linewidths at higher temperatures. We explicitly rule out the temperature dependence of intrinsic damping as a possible cause, and it is also not expected from existing extrinsic scattering mechanisms for ferromagnets. We ascribe this observation to motional narrowing, an old concept so far neglected in the analyses of FMR spectra. The effect is confirmed to originate from interfacial anisotropy, impacting the practical technology of spin-based nanodevices up to room temperature.


Comparative study of drug use among undergraduate students at the University of São Paulo--São Paulo campus in 1996 and 2001.
To compare the rate of drug use prevalence and to investigate opinions regarding such use among undergraduate students at the University of São Paulo--São Paulo campus in 1996 and again in 2001. Both studies followed the same procedures of sampling and data collection. A random sample of undergraduate students, divided into the areas Humanities, Exact Sciences and Biologic Sciences, responded to an anonymous and self-report survey regarding the use of licit and illicit drugs within the last 30 days, within the last 12 months and over the lifetime of the subject. The two surveys were compared through the construction of (95%) confidence intervals for the prevalence differences for each substance by area and by total number of students. The Wald test for homogeneity was applied in order to compare the prevalences. High approval of regularly trying and using cocaine, crack, amphetamines and inhalants was observed. The drugs that showed statistic significant increasing were:lifetime use: alcohol, tobacco, marijuana, inhalants, hallucinogens, amphetamines, anti cholines, barbiturics and any illicit drug;last-12-month use: marijuana, inhalants, amphetamines, hallucinogens and any illicit drug;last-30-day use: marijuana, inhalants, amphetamines and any illicit drug. The observed difference in the use of some drugs between the two surveys appears to be a consequence of the higher rates of favorable opinions regarding trying and regularly using some psychoactive substances, a finding that mirrors global trends in drug use.


High-Affinity Fluorogenic Substrate for Tissue Transglutaminase Reveals Enzymatic Hysteresis.
Transglutaminases (TGases) are a family of calcium-dependent enzymes primarily known for their ability to cross-link proteins. Transglutaminase 2 (TG2) is one isozyme in this family whose role is multifaceted. TG2 can act not only as a typical transamidase through its catalytic core but also as a G-protein via its GTP binding site. These two discrete activities are tightly regulated by both environmental stimuli and redox reactions. Ubiquitously expressed in humans, TG2 has been implicated in numerous disease pathologies that require extensive investigation. The catalytic activity of TG2 can be monitored through various mechanisms, including hydrolysis, transamidation, or cleavage of isopeptide bonds. Activity assays are required to monitor the activity of this isozyme not only for studying its transamidation reaction but also for validation of therapeutics designed to abolish this activity. Herein, we present the design, synthesis, and evaluation of a new TG2 activity substrate based on a previously optimized inhibitor scaffold. The substrate APH7 exhibits excellent affinity, selectivity, and reactivity with TG2 (KM = 3.0 μM). Furthermore, its application also allowed the discovery of unique hysteresis at play within the catalytic activity and inhibition reactivity of TG2.


Using negative pressure wound therapy with instillation and dwell time to create a path to closure for older patients with chronic wounds: a retrospective case series.
Chronic podiatric wounds are common causes of morbidity and mortality in older patients. Negative pressure wound therapy with instillation and dwell time (NPWTi-d) has been recommended in wounds with high levels of exudate, contaminated wounds, and wounds in which healing progression has stalled. This retrospective case series describes the use of NPWTi-d to prepare 4 chronic wounds for closure in older patients with multiple comorbidities. Patients (N = 4) ranged in age from 65 to 95 years and had wounds present for at least 90 days. Previous treatments included conventional NPWT and debridement. NPWTi-d consisted of instillation of 10 to 20 mL normal saline, dwell time for 1 minute, followed by 3-hour cycles of -125 mm Hg. Antibiotics were administered as needed. Wounds included a 210-day Wagner grade 3 diabetic foot ulcer (3.2 × 1.8 × 0.3 cm³), a 90-day dehisced wound (9.5 × 2.6 × 0.4 cm³), a 300-day neuropathic ulcer (0.7 × 0.5 × 2.1 cm³), and a 150-day Wagner grade 2 diabetic foot ulcer (4.5 × 3.3 × 0.9 cm³). NPWTi-d was applied for 3 to 33 days, when care was transitioned to advanced wound dressings. All 4 wounds responded positively to therapy, exhibiting reduced slough, growing granulation tissue, and size reduction. Closure was achieved in all cases. In these 4 patients, NPWTi-d, used as part of a treatment regimen including debridement, antibiotics, and advanced wound dressings, was effective in creating an environment that promoted wound healing and prepared the wounds for eventual closure.


Awareness, Knowledge, and Coverage of Vaccination Against Tetanus, Diphtheria, and Pertussis Among Medical Students of Karachi: A Cross-sectional Analysis.
Background Along with reducing the global burden of diphtheria, pertussis and tetanus, the DPT3 (diphtheria-pertussis-tetanus) vaccine protects health care professionals (HCPs) as well as vulnerable patients in their care. This study evaluates awareness, knowledge and coverage of DPT3 vaccine and boosters among medical students of public university in Karachi, Pakistan. Methods A cross-sectional study consisting of 281 participants selected through convenience sampling was conducted from July 2017 to July 2018 using a self-administered questionnaire. Results While 93% participants received childhood doses of DPT3, only 39.2% received adult boosters. Students with positive immunization history in childhood and family vaccination routines were more likely to get adult boosters. Eighty-six percent of the students were unaware that their university had a recommended vaccination program as a part of the admission process. The assessment of awareness and knowledge revealed that only 10.5% individuals could be regarded as well-aware, 20.3% (n = 58) students as unaware, and 69.2% (n = 198) participants as moderately aware. Conclusion The level of awareness, knowledge and coverage of DPT3 vaccine is insufficient among medical students of a public university of Karachi; universities are recommended to take measures to enhance knowledge and ensure strict adherence of students to appropriate vaccination programs.


Thyroid dysfunction in isolated adrenocorticotropic hormone (ACTH) deficiency: case report and literature review.
A case of isolated ACTH deficiency accompanying transient primary hypothyroidism was reported along with a review of literature on isolated ACTH deficiency in Japan with special reference to its association with thyroid function. Our case, a 56-year-old woman, developed somnolence and hypoglycemia due to isolated ACTH deficiency. She also had the features of hypothyroidism, namely mounding phenomenon, muscle rigidity, increased plasma myogenic enzymes and cold intolerance. Both free T3 and free T4 were decreased, and basal as well as TRH-stimulated TSH levels were abnormally high. Plasma thyroglobulin was increased and no anti-thyroid antibodies were detected. All thyroid related physical and biochemical abnormalities disappeared after hydrocortisone replacement. A review of the literature on 103 cases disclosed that more than half the cases with isolated ACTH deficiency had a high plasma level of TSH, basal and/or TRH-induced, while the antithyroid antibodies were reported to be positive in only 13 cases. In more than 70% of such cases, the abnormality in the pituitary-thyroid axis was transient and was reversed by glucocorticoid replacement. Our case and cases in the literature indicate that the interference of thyroid hormone synthesis and/or secretion by glucocorticoid deficiency per se is the major cause of thyroid dysfunction rather than associated autoimmune thyroid disease.


Development and mapping of SSR markers for maize.
Microsatellite or simple sequence repeat (SSR) markers have wide applicability for genetic analysis in crop plant improvement strategies. The objectives of this project were to isolate, characterize, and map a comprehensive set of SSR markers for maize (Zea mays L.). We developed 1051 novel SSR markers for maize from microsatellite-enriched libraries and by identification of microsatellite-containing sequences in public and private databases. Three mapping populations were used to derive map positions for 978 of these markers. The main mapping population was the intermated B73 x Mo17 (IBM) population. In mapping this intermated recombinant inbred line population, we have contributed to development of a new high-resolution map resource for maize. The primer sequences, original sequence sources, data on polymorphisms across 11 inbred lines, and map positions have been integrated with information on other public SSR markers and released through MaizeDB at URL:www.agron.missouri.edu. The maize research community now has the most detailed and comprehensive SSR marker set of any plant species.


Comparative Metabolomic Analysis Reveals the Role of OsHPL1 in the Cold-Induced Metabolic Changes in Rice.
Cytochrome P450 (CYP74) family members participate in the generation of oxylipins and play essential roles in plant adaptation. However, the metabolic reprogramming mediated by CYP74s under cold stress remains largely unexplored. Herein, we report how cold-triggered OsHPL1, a member of the CYP74 family, modulates rice metabolism. Cold stress significantly induced the expression of OsHPL1 and the accumulation of OPDA (12-oxo-phytodienoic acid) and jasmonates in the wild-type (WT) plants. The absence of OsHPL1 attenuates OPDA accumulation to a low temperature. Then, we performed a widely targeted metabolomics study covering 597 structurally annotated compounds. In the WT and hpl1 plants, cold stress remodeled the metabolism of lipids and amino acids. Although the WT and hpl1 mutants shared over one hundred cold-affected differentially accumulated metabolites (DAMs), some displayed distinct cold-responding patterns. Furthermore, we identified 114 and 56 cold-responding DAMs, specifically in the WT and hpl1 mutants. In conclusion, our work characterized cold-triggered metabolic rewiring and the metabolic role of OsHPL1 in rice.


Assessment of a newly developed, active pneumatic-driven, sensorimotor test and training device.
The sensorimotor system (SMS) plays an important role in sports and in every day movement. Several tools for assessment and training have been designed. Many of them are directed to specific populations, and have major shortcomings due to the training effect or safety. The aim of the present study was to design and assess a dynamic sensorimotor test and training device that can be adjusted for all levels of performance. The novel pneumatic-driven mechatronic device can guide the trainee, allow independent movements or disrupt the individual with unpredicted perturbations while standing on a platform. The test-reliability was evaluated using intraclass correlation coefficient (ICC). Subjects were required to balance their center of pressure (COP) in a target circle (TITC). The time in TITC and the COP error (COPe) were recorded for analysis. The results of 22 males and 14 females (23.7 ± 2.6 years) showed good to excellent test-retest reliability. The newly designed Active Balance System (ABS) was then compared with the Biodex Balance System SD® (BBS). The results of 15 females, 14 males (23.4 ± 1.6 years) showed modest correlation in static and acceptable correlation in dynamic conditions, suggesting that ABS could be a reliable and comparable tool for dynamic balance assessments.


Caged substrates applied to high content screening: an introduction with an eye to the future.
The use of photoremovable protecting groups in biology affords the end user high temporal, spatial, and concentration control of reagents and substrates. High content screening and other large-scale biology applications would benefit greatly from these advantages. Herein, we report progress in this field by highlighting the recent development of controllable siRNA (csiRNA), which is a dormant siRNA that can be activated using 365 nm light. Two different experimental designs are described to highlight the temporal and concentration variables that can be controlled. First, the RNAi process is activated at two timepoints, 24- and 48-h post-transfection, to demonstrate that the action of csiRNA does not begin until activated. Second, increasing light dosage exposure to cells transfected with csiRNA that controls the concentration of active siRNA molecules. All experiments are conducted in a 96-well format with light delivered through the UCOM device.


Angiographically Occult Subarachnoid Hemorrhage: Yield of Repeat Angiography, Influence of Initial CT Bleed Pattern, and Sources of Diagnostic Error in 242 Consecutive Patients.
Nearly 20% of patients with spontaneous SAH have no definitive source on initial DSA. The purpose of this study was to investigate the timing and yield of repeat DSA, to clarify the influence of initial CT bleed pattern, and to characterize sources of diagnostic error in this scenario. We evaluated the yield of repeat DSA and clinical outcomes stratified by hemorrhage pattern on CT in consecutive patients with nontraumatic SAH with negative initial DSA findings at a referral center. Cases in which the culprit lesion was subsequently diagnosed were classified as physiologically occult (ie, undetectable) on the initial DSA, despite adequate technique and interpretation or misdiagnosed due to operator-dependent error. Two hundred forty-two of 1163 (20.8%) patients with spontaneous SAH had negative initial DSA findings between 2009 and 2018. The SAH CT pattern was nonperimesencephalic (41%), perimesencephalic (36%), sulcal (18%), and CT-negative (5%). Repeat DSA in 135/242 patients (55.8%) revealed a source in 10 patients (7.4%): 4 saccular aneurysms, 4 atypical aneurysms, and 2 arteriovenous shunts. The overall yield of repeat DSA was 11.3% with nonperimesencephalic and 2.2% for perimesencephalic patterns. The yield of the second and third DSAs with a nonperimesencephalic pattern was 7.7% and 12%, respectively. Physiologically occult lesions accounted for 6/242 (2.5%) and operator-dependent errors accounted for 7/242 (2.9%) of all angiographically occult lesions on the first DSA. Atypical aneurysms and small arteriovenous shunts are important causes of SAH negative on angiography. Improving DSAs technique can modestly reduce the need for repeat DSA; however, a small fraction of SAH sources remain occult despite adequate technique. These findings support the practice of repeating DSA in patients with a nonperimesencephalic SAH pattern.


Antimicrobial activity of Stomoxys calcitrans against Beauveria bassiana sensu lato isolates.
This study had the aims of evaluating the antimicrobial characteristics of Stomoxys calcitrans (Diptera: Muscidae) larvae against the fungal isolates CG138, CG228 and ESALQ986 of Beauveria bassiana sensu lato (Balsamo-Crivelli) Vuillemin, 1912 (Hypocreales: Cordycipitaceae). S. calcitrans eggs, larvae and pupae were exposed to these same isolates. Statistical analysis showed that the immature stages of S. calcitrans were not susceptible to the fungal isolates used, regardless of the exposure method. Diffusion test on solid culture medium reveled that macerated S. calcitrans larvae exposed to isolate CG138 reduced CG138 fungal development. The analysis of the chromatographic profiles indicated that the macerate or mucus of larvae of the control group and the groups exposed to the isolate CG138 presented different profiles. Reduced development of the isolate CG138 on the larvae cuticle was observed by means of scanning electron microscopy.


Characterization of ESBL-producing Escherichia coli recovered from companion dogs in Tai'an, China.
Animals are considered to be reservoirs of extended-spectrum beta-lactamase (ESBL)-producing bacteria, but few epidemiological data on ESBL-producing Escherichia coli urinary tract isolates in pet dogs are available in China. This study was conducted to describe the prevalence and characterization of ESBL producers among E. coli urinary tract isolates from pet dogs in Tai'an, China. A total of 118 E. coli were obtained from urinary samples of 80 companion dogs suffering from acute or chronic cystitis, of which three isolates from different dogs were ESBL producers. One isolate from dog A was of phylogroup A/ST410/CTX-M-15/TEM-1; one from dog B was of phylogroup B1/ST533/CTX-M-15/TEM-1; one from dog C was of phylogroup D/ST648/CTX-M-15. All ESBL producers were resistant to ampicillin, cephalexin, cefalotin, cefpodoxime, ceftiofur, enrofloxacin, marbofloxacin, and trimethoprim/sulfamethoxazole, but were susceptible to imipenem and amoxicillin/clavulanic acid. E. coli of ST533 carrying blaCTX-M-15 were first detected in pet dogs in China. Collectively, the findings could expand our knowledge about the prevalence and characterization of ESBL-producing E. coli urinary tract isolates in pet dogs in China.


On the development of antifungal agents: perspective of the U.S. Food and Drug Administration.
As medical advances have prolonged the lives of patients with cancer, recipients of organ transplants, and patients with AIDS, there has been a marked increase in the number of fungal infections. Because of the known toxicity associated with amphotericin B, which has been the mainstay of therapy for systemic fungal infections, there has been a pressing need for regimens that are more effective and less toxic and that are more easily complied with by patients. This article provides a brief overview of the regulatory process of drug approval and discusses issues specific to the design of clinical trials for the treatment of systemic fungal diseases.


Overview of structure and function of mammalian cilia.
Cilia are membrane-bounded, centriole-derived projections from the cell surface that contain a microtubule cytoskeleton, the ciliary axoneme, surrounded by a ciliary membrane. Axonemes in multiciliated cells of mammalian epithelia are 9 + 2, possess dynein arms, and are motile. In contrast, single nonmotile 9 + 0 primary cilia are found on epithelial cells, such as those of the kidney tubule, but also on nonepithelial cells, such as chondrocytes, fibroblasts, and neurons. The ciliary membranes of all cilia contain specific receptors and ion channel proteins that initiate signaling pathways controlling motility and/or linking mechanical or chemical stimuli, including sonic hedgehog and growth factors, to intracellular transduction cascades regulating differentiation, migration, and cell growth during development and in adulthood. Unique motile 9 + 0 cilia, found during development at the embryonic node, determine left-right asymmetry of the body.


Composition and distribution of medically important phlebotomines (Diptera: Psychodidae) in the municipalities of Tierralta and Valencia (Córdoba, Colombia).
Ecoepidemiological studies of cutaneous leishmaniasis and regular monitoring of Lutzomyia species have generated a knowledge base that can be used for control and prevention strategies targeted at the disease transmission dynamics in focal areas of Colombia. In this study, the presence and spatial distribution of phlebotomines of medical importance in the municipalities of Tierralta (El Loro and Tuis Tuis villages) and Valencia (Guadua and Mieles villages) were determined. Entomological surveys were performed in 2015 (months of June, September and November) and samples were collected via CDC-traps located in intradomicilary and peridomiciliary areas in the municipalities of Tierralta and Valencia (Department of Córdoba, Colombia). Active searches were also carried out with a mouth aspirator to collect adult phlebotomines from resting sites. ANOVA and Kruskal-Wallis tests were performed to assess if the differences between the communities of phlebotomines. Spatial distribution maps of the Lutzomyia species were generated. A high species diversity of Lutzomyia was observed with a total of 1677 Lutzomyia individuals belonging to 12 species. Among these species, Lu. panamensis was the most abundant (80.18%). The composition of the intradomicilary and peridomiciliary phlebotomines varied significantly (F = 0.9962; df = 1; p = 0.02895). Species like Lu. carpenteri, Lu. camposi, Lu. dysponeta, Lu. atroclavata and Lu. yuilli yuilli were recorded for the first time in the Department of Córdoba, Colombia. The spatial distribution shows that Lu. panamensis and Lu. gomezi are predominant and present in areas with high concentration of houses. This study provides basic information on new records of phlebotomines in the Department of Córdoba. The results suggest that greater vector-human contact occurs in the peridomiciliary environment and that a high number of Lutzomyia species associated with the transmission of leishmaniasis are present in Colombia.


Does pregnancy increase cardiac risk for LQT1 patients with the KCNQ1-A341V mutation?
The purpose of this study was to assess the pregnancy-related cardiovascular risk in LQT1 patients. Only 1 study addressed this issue in genotyped patients and reported that the highest risk is for LQT2 patients. This case-control study, performed in a cohort of patients from 22 families affected by LQT1 and all sharing the common KCNQ1-A341V mutation, involved 36 mutation carriers and 24 of their unaffected sisters for a total of 182 pregnancies. There were 3 (2.6%) cardiac events (2 cardiac arrests) in the 115 LQT1 pregnancies. Because they occurred only among the 27 mothers with previous symptoms, all off-therapy, the risk for symptomatic patients is 11%, but decreases to 0 in symptomatic patients treated with beta-blockers. Carriers and control subjects did not differ for the incidence of miscarriage (10% vs. 15%). Cesarean sections (C-sections), elective or owing to fetal distress, were performed more often in carriers than in non-carriers (27% vs. 14%). Beta-blocker therapy did not influence the prevalence of fetal distress. Among the infants born to carriers, all those with fetal distress were carriers of the A341V mutation (10 of 10, 100%). Among the offspring of the carriers, 48 of 92 (52%) were mutation carriers, and of those, 15% died suddenly at age 14 +/- 6 years. Women affected by the common KCNQ1-A341V mutation are at low risk for cardiac events during pregnancy and without excess risk of miscarriage; their infants delivered by C-section because of fetal distress are extremely likely to also be mutation carriers. Beta-blockers remain recommended. These conclusions likely apply to most LQT1 patients.


Identification of Post-myocardial Infarction Blood Expression Signatures Using Multiple Feature Selection Strategies.
Myocardial infarction (MI) is a type of serious heart attack in which the blood flow to the heart is suddenly interrupted, resulting in injury to the heart muscles due to a lack of oxygen supply. Although clinical diagnosis methods can be used to identify the occurrence of MI, using the changes of molecular markers or characteristic molecules in blood to characterize the early phase and later trend of MI will help us choose a more reasonable treatment plan. Previously, comparative transcriptome studies focused on finding differentially expressed genes between MI patients and healthy people. However, signature molecules altered in different phases of MI have not been well excavated. We developed a set of computational approaches integrating multiple machine learning algorithms, including Monte Carlo feature selection (MCFS), incremental feature selection (IFS), and support vector machine (SVM), to identify gene expression characteristics on different phases of MI. 134 genes were determined to serve as features for building optimal SVM classifiers to distinguish acute MI and post-MI. Subsequently, functional enrichment analyses followed by protein-protein interaction analysis on 134 genes identified several hub genes (IL1R1, TLR2, and TLR4) associated with progression of MI, which can be used as new diagnostic molecules for MI.


Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib.
Ibrutinib is associated with bleeding-related adverse events of grade ≤ 2 in severity, and infrequently with grade ≥ 3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ≤ 2 bleeding-related adverse events in 55% of 85 patients. No grade ≥ 3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months, suggesting that the risk of bleeding decreases with continued therapy. At baseline, von Willebrand factor and factor VIII levels were often high and normalized on treatment. Platelet function measured via the platelet function analyzer (PFA-100™) was impaired in 22 patients at baseline and in an additional 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not. Compared to untreated chronic lymphocytic leukemia patients, response to collagen showed a mild further decrement on ibrutinib, while response to adenosine diphosphate improved. All parameters associated with a significantly increased risk of bleeding-related events were present at baseline, including prolonged epinephrine closure time (HR 2.74, P=0.012), lower levels of von Willebrand factor activity (HR 2.73, P=0.009) and factor VIII (HR 3.73, P=0.0004). In conclusion, both disease and treatment-related factors influence the risk of bleeding. Patients at greater risk for bleeding of grade ≤ 2 can be identified by clinical laboratory tests and counseled to avoid aspirin, non-steroidal anti-inflammatory drugs and fish oils. ClinicalTrials.gov identifier NCT01500733.


PHYSICAL THERAPY INTERVENTION FOR MEDIAL PATELLOFEMORAL LIGAMENT RECONSTRUCTION AFTER REPEATED LATERAL PATELLAR SUBLUXATION/DISLOCATION.
The incidence of patellar subluxation or dislocation has been documented up to 43/100,000 with females more prevalent then males. There are many contributing factors involving the hip, knee, and ankle that lead to patellar subluxation. A patellar position of lateral tilt with lateral glide may indicate weakness of the vastus medialis oblique (VMO) and adductors, increased tightness in the iliotibial band, and overpowering of the vastus lateralis. Patella alta can predispose an individual to lateral dislocation due to the patella placement outside of the femoral trochlear groove with a disadvantage of boney stability. Other factors that may cause the patella to laterally sublux or dislocate during a functional activity or sporting activity include a position of femoral external rotation, tibial internal rotation, and excessive contraction of the vastus lateralis. The medial patellofemoral ligament (MPFL) aids in the prevention of a lateral patellar subluxation or dislocation. In cases where there is recurrent subluxation/dislocation and Magnetic Resonance Imaging confirms a MPFL tear, a reconstruction may be the treatment of choice. The purpose of this case series is to describe the post-surgical physical therapy management of MPFL reconstructions, outcomes using the Modified Cincinnati Knee Outcome Measure (MCKOM) and to propose staged physical therapy interventions for this pathology in the form of a treatment progression. Post-operative management data and outcomes were retrospectively collected using a detailed chart review methodology from seven subjects who underwent MPFL reconstruction. The Modified Cincinnati Knee Outcome Measure (MCKOM) was analyzed for each participant in four sections that were most important to the return and maintenance of participation in sport. At follow-up the mean scores for the seven subjects in Section 3 (instability) was 19.3/20, Section 4 (overall activity level) was 17.3/20, Section 7 (running activity) was 4.5/5, and Section 8 (jumping and twisting) was 4.3/5. Overall all subjects scored over an 80 which indicated excellent results for return to activity/sport. In this case series, seven subjects after MPFL reconstruction returned to sport or functional activity following a physical therapy treatment progression including proprioceptive-focused, and dynamic rehabilitation, along with a home exercise program. Based on these positive results and a review of relevant literature regarding MPFL rehabilitation, a rehabilitation progression was presented. Level 4- Case Series.


Antimildew Effect of Three Phenolic Compounds and the Efficacy of Antimildew Sliced Bamboo Veneer.
The development of the bamboo industry has been hindered by environmental issues caused by the application of bamboo preservatives. Chinese herbal phenolic compounds have been shown to possess broad-spectrum, potent antimildew properties, making them promising candidates for the development of new bamboo mildew inhibitors. In this study, we investigated the antimildew properties of three phenolic compounds, eugenol, carvacrol, and paeonol, against common mildews in bamboo materials using the Oxford cup method and the double-dilution method. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to analyze the antimildew mechanism and its effects on mildew cell morphology. Our results showed that carvacrol exhibited the strongest antimildew activity, with minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values of 1.56 mg/mL and 1.76 mg/mL, respectively, followed by eugenol and paeonol. At a concentration of 25 mg/mL, eugenol and carvacrol had an inhibitory rate of over 50% against various mildews. Different concentrations of the three compounds significantly disrupted the morphology and structural integrity of mildew hyphae, with the extent of damage increasing with concentration and treatment duration. In the sliced bamboo mildew prevention experiment, carvacrol at a concentration of 29.25 mg/mL was found to be highly effective against all tested mildews. Our study provides new insights and a theoretical basis for the development of eco-friendly bamboo mildew inhibitors based on plant phenolic compounds.


[Neuroprotective mechanisms of vascular endothelial growth factor].
Vascular endothelial growth factor (VEGF), originally discovered in tumor cells, is an angiogenic factor essential for new blood vessel formation during embryogenesis and in many pathological conditions. There is a growing body of evidence that VEGF can act directly on neurons and plays a new role as a neuroprotective factor via multiple mechanisms. Moreover, VEGF modulates neurogenesis in constitutive neurogenic and non-neurogenic regions of adult mammalian brains, which is a promising therapeutic strategy for neuronal replacement in traumatic brain injury and neurodegenerative diseases. Here, we mainly reviewed the neuroprotection of VEGF against ischemic brain injury and its mechanisms.


Effect of propranolol and pindolol on the up-regulation of lymphocytic beta adrenoceptors during acute submaximal physical exercise. A placebo-controlled double-blind study.
The effect of beta-adrenoceptor antagonists, with and without intrinsic sympathomimetic activity, on the regulation of lymphocytic beta adrenoceptors during acute physical exercise was studied. Seven healthy volunteers underwent a graded maximal ergometer test after treatment for 7 days with placebo, propranolol (2 x 80 mg/day), or pindolol (2 x 10 mg/day). Each subject received the three types of drug treatment in a double-blind, randomized fashion, with 3 weeks wash-out periods between the on-drug periods. The mean resting density of lymphocytic beta adrenoceptors was 46 +/- 5 fmol/mg protein (mean +/- SEM) during placebo, 53 +/- 5 fmol/mg protein during propranolol, and 29 +/- 4 fmol/mg protein during pindolol treatment (p less than 0.05, pindolol vs. propranolol). Exercise induced a significant up-regulation of the beta-adrenoceptor density during each treatment modality, but the increment was attenuated during propranolol (mean elevation, 16 +/- 2 fmol/mg protein, p less than 0.05) and pindolol intake (13 +/- 4 fmol/mg protein, p less than 0.02) as compared with the placebo value (56 +/- 13 fmol/mg protein). Moreover, exercise-induced increment of lymphocytic cyclic AMP (cAMP) production was virtually abolished by the two beta-adrenoceptor antagonists. In conclusion, administration of beta-adrenoceptor antagonists is associated with a subnormal up-regulation of the lymphocytic beta-adrenoceptors and alterations in their functioning during heavy physical effort. This attenuation is not modified by intrinsic sympathomimetic activity of the compound.


Research and Forecast Analysis of Financial Stability for Policy Uncertainty.
The instability of financial market will have a great impact on money, bonds, and stocks and affect the economic development of society and people's lives. Therefore, it is very necessary for us to study and predict the financial stability. According to the forecast results, we will analyze and make a series of preparatory measures. First, we make a series of analyses on the structure and significance of policy uncertainty and financial stability. This paper introduces the advantages and disadvantages of the P/L model, the KLS signal method, and the BP neural network model for financial stability early warning, It is clearly pointed out that the BP neural network is more reliable and accurate, Then, the BP neural network, the ant colony algorithm, and the genetic algorithm are used to predict the opening price, closing price, highest price, and lowest price of KDJ index of Cathay Pacific Group's 5-day data. Compared with the real value, we find that the BP neural network is almost the smallest in forecasting the opening price and closing price, or the lowest price and the highest price, and has good stability, which once again proves the feasibility of applying the BP neural network to the research and prediction of financial stability.


Development of convergent synaptic inputs to subpopulations of autonomic neurons.
Visceromotor neurons in mammalian prevertebral sympathetic ganglia receive convergent synaptic inputs from spinal preganglionic neurons and peripheral intestinofugal neurons projecting from the enteric plexuses. Vasomotor neurons in the same ganglia receive only preganglionic inputs. How this pathway-specific pattern of connectivity is established is unknown. We have used a combination of immunohistochemical, ultrastructural, and electrophysiological techniques to investigate the development of synaptic inputs onto visceromotor and vasomotor neurons in the celiac ganglion of guinea pigs. Functional synaptogenesis occurred primarily from early fetal (F30-F35) to midfetal (F36-F45) stages, after the neurochemical differentiation of vasomotor and visceromotor neurons but before establishment of their electrophysiological phenotypes. Intestinofugal inputs were detected only on presumptive visceromotor neurons located primarily in medial regions of the ganglion. The number of ultrastructurally identified synaptic profiles increased in parallel with functional synaptogenesis, especially in medial regions, where dendritic growth rates also were higher. However, the expression of immunoreactivity to choline acetyltransferase in the terminals of inputs was very low until late fetal stages, after functional transmission already had been established. These results show that peripheral intestinofugal neurons directly establish appropriate functional connections with their target visceromotor neurons simultaneously with the development of functional preganglionic inputs to both visceromotor and vasomotor neurons. It seems likely that synaptogenesis occurs independently of the neurochemical differentiation of the target neurons but is closely related to the pathway-specific dendritic development of those neurons.


Neuroimaging investigation of the intracranial vasculature is warranted in older adults with lacunes of presumed vascular origin.
Lacunes of presumed vascular origin are perceived as biomarkers of cerebral small vessel disease (cSVD), although they may also be related to other pathogenetic mechanisms. We aimed to assess whether lacunes are more often associated with intracranial artery stenosis (IAS) than with white matter hyperintensities (WMH) of presumed vascular origin (a biomarker of cSVD) in older adults. This study included 585 individuals aged ≥60 years living in rural Ecuador. Logistic regression models were fitted to assess the strength of the association between IAS or moderate-to-severe WHM on one side, and lacunes on the other. Mediation analysis was used to estimate the percentage of the effect of IAS on lacunes that was mediated by WMH. Lacunes were noticed in 62 (11%) individuals, IAS in 39 (7%), and moderate-to-severe WMH in 169 (29%). Fourteen of 39 individuals (36%) with IAS had lacunes, which corresponded to the territory of the stenotic artery in 50% of cases. Lacunes have a larger association with IAS than with moderate-to-severe WMH. The estimated prevalence rate of lacunes independently of any confounder was 10.6% (95% C.I.: 8.3-12.9%), which increased to 22.2% in subjects with IAS, but only to 16.4% among those with moderate-to-severe WMH. Only 24.5% of the effect of IAS on lacunes was mediated by WMH. Lacunes are more often associated with IAS than with WMH at the population level. Neuroimaging investigation of the intracranial vasculature in individuals with lacunes will provide informed-based decisions for secondary stroke prevention.


Efficacy and safety of beclomethasone dipropionate breath-actuated or metered-dose inhaler in pediatric patients with asthma.
Breath-actuated inhalers (BAI) eliminate the need for hand-breath coordination and, therefore, simplify the delivery of inhaled medication. To evaluate the efficacy and safety of beclomethasone dipropionate BAI and metered-dose inhaler (MDI) versus placebo in pediatric patients ages 4-11 years with persistent asthma. In this double-blind, double-dummy, phase III study, 628 children with persistent asthma were randomly assigned (1:1:1:1:1) to twice-daily beclomethasone dipropionate (BAI 80 μg/day, BAI 160 μg/day, MDI 80 μg/day, or MDI 160 μg/day) or to placebo. Efficacy over 12 weeks was assessed by spirometry, peak expiratory flow (PEF) measurements and other clinical end points. The primary efficacy end point was the baseline-adjusted trough morning percent predicted forced expiratory volume in 1 second (PPFEV1) area under the effect curve from 0 to 12 weeks (AUEC[0-12 weeks]). PPFEV1 AUEC(0-12 weeks) showed numerical improvements from baseline in the BAI 80 μg/day and BAI 160 μg/day groups and MDI 80 μg/day and MDI 160 μg/day groups; however, these improvements were not significant versus placebo for any group after hierarchical testing was applied. Consistent improvements were noted in the active treatment groups versus placebo for the weekly average trough morning and evening PEFs, and with BAI 80 μg/day versus placebo for rescue albuterol/salbutamol use and the total daily asthma symptom score. Most patients indicated that the BAI device was easy or very easy to use. Adverse events were comparable across the groups; the incidence of oral candidiasis ranged from 0.8 to 3.2%. Although the primary efficacy end point was not demonstrated, consistent improvements in PEF and other clinical end points were observed with beclomethasone dipropionate BAI, particularly at the 80 μg/day dose. These clinical benefits, combined with the need for better symptom control in children with asthma, supported the development of beclomethasone dipropionate BAI.


High contrast Kr gas jet K alpha x-ray source for high energy density physics experiments.
A high contrast 12.6 keV Kr K alpha source has been demonstrated on the petawatt-class Titan laser facility using strongly clustering Kr gas jet targets. The contrast ratio (K alpha to continuum) is 65, with a competitive ultrashort pulse laser to x-ray conversion efficiency of 10(-5). Filtered shadowgraphy indicates that the Kr K alpha and K beta x rays are emitted from a roughly 1x2 mm(2) emission volume, making this source suitable for area backlighting and scattering. Spectral calculations indicate a typical bulk electron temperature of 50-70 eV (i.e., mean ionization state 13-16), based on the observed ratio of K alpha to K beta. Kr gas jets provide a debris-free high energy K alpha source for time-resolved diagnosis of dense matter.


Does gamification increase engagement with online programs? A systematic review.
Engagement in online programs is difficult to maintain. Gamification is the recent trend that offers to increase engagement through the inclusion of game-like features like points and badges, in non-game contexts. This review will answer the following question, 'Are gamification strategies effective in increasing engagement in online programs?' Eight databases (Web of Science, PsycINFO, Medline, INSPEC, ERIC, Cochrane Library, Business Source Complete and ACM Digital Library) were searched from 2010 to the 28th of October 2015 using a comprehensive search strategy. Eligibility criteria was based on the PICOS format, where "population" included adults, "intervention" involved an online program or smart phone application that included at least one gamification feature. "Comparator" was a control group, "outcomes" included engagement and "downstream" outcomes which occurred as a result of engagement; and "study design" included experimental studies from peer-reviewed sources. Effect sizes (Cohens d and 95% confidence intervals) were also calculated. 1017 studies were identified from database searches following the removal of duplicates, of which 15 met the inclusion criteria. The studies involved a total of 10,499 participants, and were commonly undertaken in tertiary education contexts. Engagement metrics included time spent (n = 5), volume of contributions (n = 11) and occasions visited to the software (n = 4); as well as downstream behaviours such as performance (n = 4) and healthy behaviours (n = 1). Effect sizes typically ranged from medium to large in direct engagement and downstream behaviours, with 12 out of 15 studies finding positive significant effects in favour of gamification. Gamification is effective in increasing engagement in online programs. Key recommendations for future research into gamification are provided. In particular, rigorous study designs are required to fully examine gamification's effects and determine how to best achieve sustained engagement.


Psychometric Evaluation of the Cognitive State Test (COST) in a Sample of Iranian Elderly People.
An absolute prerequisite to the effective management of dementia is its early diagnosis. Successful dementia screening requires precise and sensitive instruments that can be completed even by illiterate elderly people. The aim of this study was to evaluate the psychometric properties of the Persian version of the cognitive state test (COST). This methodologic study was conducted in Kashan, Iran, during 2013 - 2014. A purposeful sample of 150 healthy elderly people and 50 elderly patients with dementia was recruited. After translating the instrument by using the standard forward-backward technique, we assessed its qualitative and quantitative face and content validity. The validity of the test was assessed by using the concurrent validity and the exploratory factor analysis. We also calculated Cronbach's alpha and employed the test-retest method for evaluating the internal consistency and the stability of the test, respectively. Study data were analyzed by using the SPSS v16.0, the Spearman-Brown, and the intraclass correlation coefficient tests and the principal components factor analysis with varimax rotation. The Persian COST consists of nineteen items. The impact scores, the content validity ratios and the content validity indices of all test items were greater than 4.5, 0.69, and 0.84, respectively. The COST had a significant correlation with the clinical dementia rating (rS = -0.76, P value < 0.001), indicating an acceptable concurrent validity for the test. The exploratory factor analysis revealed a five-factor structure that explained 60.59% of the total variance of the total cognitive state score. The Cronbach's alpha, Spearman-Brown, and interclass correlation coefficients were 0.82, 0.95, and 0.88, respectively (P value < 0.001). The Persian version of the COST can be used as a valid and reliable instrument for assessing cognitive state and screening dementia in literate and illiterate elderly people.


Standardizing antimicrobial disk sensitivity testing.
Before antimicrobial sensitivity testing, any pathogens must be isolated by streaking the clinical specimen on a plate of nutritive medium. Selecting a drug based on tests of a mixed culture from which a pathogen has not been isolated encourages unnecessary treatment. A plate of Mueller-Hinton agar is swabbed with an inoculum from a standardized broth culture. Drug-impregnated paper disks are applied to the plate at least 3 cm apart and at least 2 cm from the plate's edge. The zone of inhibition varies with each drug and is measured, after overnight incubation at 35-37 C, with the aid of over-the-shoulder lighting and a dark background.


[Application value of color Doppler ultrasonography in the diagnosis of ruptured tunica albuginea of the corpus cavernosum penis].
To assess the accuracy and value of ultrasonography in the diagnosis of ruptured tunica albuginea (RTA) of the corpus cavernosum penis. Factors affecting prognosis were analyzed. This retrospective study included 57 cases of RTA of the corpus cavernosum penis ultrasonographically diagnosed and surgically treated in Peking University First Hospital from 2013 to 2021. We analyzed the location, size and number of ruptures and the presence or absence of urethral injury, and compared the intraoperative with the ultrasonographic findings. Of the 57 cases of RTA of the corpus cavernosum penis diagnosed by ultrasonography, 54 (94.7%) were confirmed by surgery. Preoperative ultrasonography indicated 2 cases of bilateral RTA and 6 cases of urethral injury, while surgery revealed 7 cases of bilateral RTA and 13 cases of combined urethral injury. Those with urethral injury developed no urethral stricture or urinary fistula after one-stage urethral repair. And no severe or moderate ED was found in any of the patients during the 12-month follow-up. Ultrasonography has a high accuracy in the diagnosis of ruptured tunica albuginea of the corpus cavernosum penis, and contributes to the determination of the site of surgical incision.


Risk Factors for Self-injurious Behavior in an Inpatient Psychiatric Sample of Children with Autism Spectrum Disorder: A Naturalistic Observation Study.
Limited information about self-injurious behavior (SIB) is known for children and adolescents with Autism Spectrum Disorder (ASD) who require intensive behavioral health interventions. We examined risk-factors for SIB in 302 individuals with ASD (ages 4-20) admitted to six specialized psychiatric inpatient units. Seventy-four percent were reported by a caregiver to display SIB, however, only 25% were observed to engage in daily SIB during hospitalization. Those exhibiting SIB across environments had significantly higher ratings on caregiver questionnaires of SIB severity. Tree-structured classification was used to develop and validate two predictive models, one indicating which inpatient youth with ASD are likely to have SIB and a second indicating which individuals with SIB at home are likely to continue in an inpatient setting.


Oncocytic adrenocortical carcinomas: a pathological and immunohistochemical study of four cases in comparison with conventional adrenocortical carcinomas.
Clinicopathological features of four cases of oncocytic adrenocortical carcinomas were studied. All tumors were large, circumscribed tumors with average size and weight of 11.5 cm and 586 g, respectively. The cut surfaces were yellow or brown and tan with areas of hemorrhage, necrosis, fibrosis, myxoid and cystic change. The tumor cells were exclusively oncocytic with a diffuse or compact and solid arrangement. Nuclear atypia was identified but mitosis was rare. Capsular invasion was identified in all tumors and vascular invasion was identified in one tumor. All tumors were immunoreactive for vimentin and inhibins. Immunoreactivity for pancytokeratin, synaptophysin and S-100 protein was variable and focal. All tumors had low proliferative indices, of less than 1%, and were negative for p53 protein. Ultrastructurally, the cytoplasm of tumor cells showed numerous mitochondria in a compact arrangement. Oncocytic adrenocortical carcinomas showed a similar sex ratio, slightly older mean age, similar left predilection, slightly smaller size and lighter weight compared with the conventional carcinomas. We suggest that most oncocytic adrenocortical carcinomas might be low-grade malignancies with less aggressive histological features compared with conventional carcinomas. However, they should be excised completely because of the likelihood of recurrence and metastasis during the follow-up period.


How camouflage works.
For camouflage to succeed, an individual has to pass undetected, unrecognized or untargeted, and hence it is the processing of visual information that needs to be deceived. Camouflage is therefore an adaptation to the perception and cognitive mechanisms of another animal. Although this has been acknowledged for a long time, there has been no unitary account of the link between visual perception and camouflage. Viewing camouflage as a suite of adaptations to reduce the signal-to-noise ratio provides the necessary common framework. We review the main processes in visual perception and how animal camouflage exploits these. We connect the function of established camouflage mechanisms to the analysis of primitive features, edges, surfaces, characteristic features and objects (a standard hierarchy of processing in vision science). Compared to the commonly used research approach based on established camouflage mechanisms, we argue that our approach based on perceptual processes targeted by camouflage has several important benefits: specifically, it enables the formulation of more precise hypotheses and addresses questions that cannot even be identified when investigating camouflage only through the classic approach based on the patterns themselves. It also promotes a shift from the appearance to the mechanistic function of animal coloration.This article is part of the themed issue 'Animal coloration: production, perception, function and application'.


Studies on the existence of synergism between different antibiotics and a phenothiazine tranquilizer, promazine, possessing antimicrobial property.
Different antibiotics were tested for their capacity to exhibit synergism when used in combination with promazine (Pr), a tranquilizer endowed with powerful antimicrobial property. For this purpose the minimum inhibitory concentration (MIC) of different antibiotics and Pr was first determined by spot inoculation technique on nutrient agar plates to select the concentrations of the antibiotics and Pr to be used as well as the sensitive strains. It was observed that Pr in combination with tetracycline (Tc) demonstrated a marked enhancement of the inhibitory capacity of each drug, both against the Gram-positive and Gram-negative bacteria, following disc diffusion technique. The in vitro findings were further substantiated with the in vivo effects of Pr along with Tc using Salmonella typhimurium NCTC 74 as the challenge strain in mice. The synergism obtained was further corroborated in terms of the increase in the size of their inhibition zones compared with their unaltered individual zones to determine the level of significance. This result was also confirmed by the checkerboard test using doubling dilutions of both the agents.


Management of acute diarrhea.
Acute diarrhea in adults is usually caused by bacterial infection, parasitic infestation, food poisoning, or drugs. In this review, we summarize the pros and cons of medical therapies, point out certain areas of controversy, and propose a rationale for early intervention. Discussion is limited to the use of antidiarrheal agents and antibiotics in acute infectious diarrhea.


Elucidation of molecular targets of bioactive principles of black cumin relevant to its anti-tumour functionality - An Insilico target fishing approach.
Black cumin (Nigella sativa) is a spice having medicinal properties with pungent and bitter odour. It is used since thousands of years to treat various ailments, including cancer mainly in South Asia and Middle Eastern regions. Substantial evidence in multiple research studies emphasizes about the therapeutic importance of bioactive principles of N. sativa in cancer bioassays; however, the exact mechanism of their anti-tumour action is still to be fully comprehended. The current study makes an attempt in this direction by exploiting the advancements in the Insilico reverse screening technology. In this study, three different Insilico Reverse Screening approaches have been employed for identifying the putative molecular targets of the bioactive principles in Black cumin (thymoquinone, alpha-hederin, dithymoquinone and thymohydroquinone) relevant to its anti-tumour functionality. The identified set of putative targets is further compared with the existing set of experimentally validated targets, so as to estimate the performance of insilico platforms. Subsequently, molecular docking simulations studies were performed to elucidate the molecular interactions between the bioactive compounds & their respective identified targets. The molecular interactions of one such target identified i.e. VEGF2 along with thymoquinone depicted one H-bond formed at the catalytic site. The molecular targets identified in this study need further confirmatory tests on cancer bioassays, in order to justify the research findings from Insilico platforms. This study has brought to light the effectiveness of usage of Insilico Reverse Screening protocols to characterise the un-identified target-ome of poly pharmacological bioactive agents in spices.


Oxidized Milk Induces Spatial Learning and Memory Impairment by Altering Gut Microbiota in Offspring Mice during Pregnancy and Lactation.
Early adverse diet exposures are known to be associated with increased risk of learning and memory injury in offspring, yet whether oxidized milk is involved in such an effect has been largely unknown. Here, we focused on oxidized milk intake in mice during pregnancy and lactation to measure the changes in the learning and memory ability in offspring and also probed into the relevant association with gut microbiota. Milk was oxidized with H2O2-Cu or HClO, resulting in different degrees of oxidative damage. KM female mice were fed H2O2-Cu, HClO, or normal control diets immediately after caging until their offspring were 3-weeks old. Behavioral tests were then performed to test the learning and memory ability, and 16S rRNA sequencing was completed with harvested fecal contents. As analyzed, fecal microflora in mice with oxidized milk was affected, mainly reflected in decreased mucin-degrading bacteria, Akkermansia and Lactobacillus, and in reversely increased pro-inflammatory bacteria Shigella, pathobiont Mucispirillum, nervous associated bacteria Ruminococcus, Escherichia, and Desulfovibrio. In the meantime, the inflammation developed in mice was aggravated accompanied by increased expression of relevant genes, while the genes and proteins associated with the learning and memory ability were down-regulated. Further behavioral tests proved impairment of the learning and memory ability in offspring. In general, milk of oxidative damage is a risk factor of the impaired transgenerational ability in learning and memory, which is associated with gut microbiota and intestinal mucosa conditions. This finding may help support the potential of early adverse diet as a harmful factor in learning and memory.


Luminescence Fine Structures in Single Lead Halide Perovskite Nanocrystals: Size Dependence of the Exciton-Phonon Coupling.
Lead halide perovskite nanocrystals (NCs) have superior photoluminescence (PL) properties, such as high PL quantum yields and wide PL wavelength tunability, for optoelectronic applications. Here, we report the PL spectra of single formamidinium lead halide perovskite FAPbX3 (X = Br, I) NCs examined by single-dot spectroscopy at low temperature. We found four PL peaks in the low-energy region below the strong exciton PL peak that originate from two longitudinal-optical (LO) phonon replicas of the exciton PL, biexcitons, and charged excitons (trions). The binding energies of the biexcitons and trions become larger as the NCs decrease in size. The LO phonon energies show no size dependence, but the Huang-Rhys factors, which reflect the strength of the exciton-phonon coupling, become larger for smaller NCs. Our findings provide important insights into the exciton properties of perovskite NCs.