Maternal and cord blood miR-223 expression associates with prenatal tobacco smoke exposure and low regulatory T-cell numbers.
There is evidence that microRNAs (miRNAs) are sensitive to environmental stressors, including tobacco smoke. On the other hand, miRNAs are involved in immune regulation, such as regulatory T (Treg) cell differentiation. The aim of the present study was to investigate the association between prenatal tobacco smoke exposure, miRNAs, and Treg cell numbers. Within a prospective mother-child study (Lifestyle and Environmental Factors and Their Influence on Newborns Allergy Risk), we analyzed the expression of miR-155 and miR-223 together with Treg cell numbers in maternal blood during pregnancy, as well as in cord blood (n = 441). Tobacco smoke exposure was assessed based on questionnaire answers and maternal urine cotinine levels. Additionally, the concentration of smoking-related volatile organic compounds was measured in dwellings of study participants. Both maternal and cord blood miR-223 expressions were positively correlated with maternal urine cotinine levels. An association was also found between maternal miR-223 expression and indoor concentrations of benzene and toluene. High miR-223 expression was associated with lower Treg cell numbers in maternal and cord blood. Furthermore, children with lower Treg cell numbers at birth had a higher risk of atopic dermatitis during the first 3 years of life. The concentration of the toluene metabolite S-benzylmercapturic acid in maternal urine was associated with decreased cord blood, but not maternal blood, miR-155 expression. A relationship between miR-155 expression and Treg cell numbers was not found. For the first time, we show that maternal tobacco smoke exposure during pregnancy correlates with the level of miRNA-223 expression in blood, with an effect on children's cord blood Treg cell numbers and subsequent allergy risk.


Short- and long-term functional results following drug-coated balloons versus drug- eluting stents in small coronary vessels: The RESTORE quantitative flow ratio study.
Background Immediate and long-term functional outcomes after percutaneous treatment of small vessel disease (SVD) with drug-coated balloon (DCB) versus drug-eluting stent (DES) remain unknown. The study sought to investigate whether treatment of de novo SVD with DCB yields similar functional results compared with DES, as judged with angiography-based quantitative flow ratio (QFR). Methods and results QFR was measured at pre-procedural, post-procedural and 9-month angiography in all available subjects from the non-inferiority RESTORE SVD China trial, in which patients were randomized to Restore DCB (n = 116) or Resolute DES (n = 114) study arms. Primary outcome of this analysis was 9-month QFR. Pre-procedural, post-procedural and 9-month QFR was performed in 84.8% (195/230), 83.0% (191/230) and 93.8% (181/193) cases, respectively. At 9 months, the QFR of DCB showed no significant difference to DES (0.88 ± 0.23 vs. 0.92 ± 0.12, p = 0.12). Both 9-month QFR and the QFR difference between post-procedure and 9-month follow-up were correlated with angiographic percentage of diameter stenosis and late loss, and predictive of 2-year clinical outcome. Conclusions Treatment of coronary SVD with DCB resulted in similar 9-month functional results compared with DES. This study provides evidences to the value of QFR as a mean of evaluating device performance after coronary revascularization. Clinical trial registration URL: https://www.clinicaltrials.gov; ClinicalTrial.gov: Identifier: NCT02946307.


Building optimal regression tree by ant colony system-genetic algorithm: application to modeling of melting points.
The classification and regression trees (CART) possess the advantage of being able to handle large data sets and yield readily interpretable models. A conventional method of building a regression tree is recursive partitioning, which results in a good but not optimal tree. Ant colony system (ACS), which is a meta-heuristic algorithm and derived from the observation of real ants, can be used to overcome this problem. The purpose of this study was to explore the use of CART and its combination with ACS for modeling of melting points of a large variety of chemical compounds. Genetic algorithm (GA) operators (e.g., cross averring and mutation operators) were combined with ACS algorithm to select the best solution model. In addition, at each terminal node of the resulted tree, variable selection was done by ACS-GA algorithm to build an appropriate partial least squares (PLS) model. To test the ability of the resulted tree, a set of approximately 4173 structures and their melting points were used (3000 compounds as training set and 1173 as validation set). Further, an external test set containing of 277 drugs was used to validate the prediction ability of the tree. Comparison of the results obtained from both trees showed that the tree constructed by ACS-GA algorithm performs better than that produced by recursive partitioning procedure.


Spiritual care experiences by cancer patients, their family caregivers and healthcare team members in oncology practice settings: A qualitative study.
Integrating spirituality into the patient care within a healthcare team, increases the ability to provide "holistic care" for cancer patients. The spiritual care experiences of different involved persons can be a guide for future planning. Therefore, this study aimed to explore the spiritual care experiences of hospitalized cancer patients, their family caregivers and healthcare team members in oncology settings. This is a descriptive qualitative study which was conducted with 21 participants, who were selected by purposive sampling. Semi-structured interviews were used to collect the data. The data were analyzed with conventional content analysis method. Two themes of "systematic care" and "caring with paradoxical results" were extracted from the spiritual care experiences of our participants. Spiritual care as professional, comprehensive, collaborative and artistic care should be provided in a multidisciplinary healthcare team for cancer patients. Otherwise, patients may experience deprivation of spiritual services and consequently, spiritual distress.


Diagonal reverse-phase chromatography applications in peptide-centric proteomics: ahead of catalogue-omics?
Diagonal electrophoresis/chromatography was described 40 years ago and was used to isolate specific sets of peptides from simple peptide mixtures such as protease digests of purified proteins. Recently, we have adapted the core technology of diagonal chromatography so that the technique can be used in so-called gel-free, peptide-centric proteome studies. Here we review the different procedures we have developed over the past few years, sorting of methionyl, cysteinyl, amino terminal, and phosphorylated peptides. We illustrate the power of the technique, termed COFRADIC (combined fractional diagonal chromatography), in the case of a peptide-centric analysis of a sputum sol phase sample of a patient suffering from chronic obstructive pulmonary disease (COPD). We were able to identify an unexpectedly high number of intracellular proteins next to known biomarkers.


PI3K inhibitor GDC-0941 enhances apoptotic effects of BH-3 mimetic ABT-737 in AML cells in the hypoxic bone marrow microenvironment.
Both phosphatidylinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin signaling and antiapoptotic Bcl-2 family members are critical for survival of acute myeloid leukemia (AML) cells. Here, we demonstrate the antileukemic effects of simultaneous inhibition of PI3K by the selective class I PI3K inhibitor GDC-0941 and of Bcl-2 family members by the BH3 mimetic ABT-737 in the context of the bone marrow microenvironment, where hypoxia and interactions with bone marrow stromal cells promote AML cell survival and chemoresistance. The combination of GDC-0941 and ABT-737 profoundly downregulated antiapoptotic Mcl-1 expression levels, activated BAX, and induced mitochondrial apoptosis in AML cells co-cultured with bone marrow stromal cells under hypoxic conditions. Hypoxia caused degradation of Mcl-1 and rendered Mcl-1-overexpressing OCI-AML3 cells sensitive to ABT-737. Our findings suggest that pharmacologic PI3K inhibition by GDC-0941 enhances ABT-737-induced leukemia cell death even under the protective conditions afforded by the bone marrow microenvironment. Combined blockade of PI3K and Bcl-2 pathways down-regulates anti-apoptotic Mcl-1 expression PI3K and Bcl-2 induced Mcl-1 down-regulation activates BAX PI3K and Bcl-2 blockage induces apoptosis in AML under hypoxic BM microenvironment.


The role of clinical phenotypes in decisions to limit life-sustaining treatment for very old patients in the ICU.
Limiting life-sustaining treatment (LST) in the intensive care unit (ICU) by withholding or withdrawing interventional therapies is considered appropriate if there is no expectation of beneficial outcome. Prognostication for very old patients is challenging due to the substantial biological and functional heterogeneity in that group. We have previously identified seven phenotypes in that cohort with distinct patterns of acute and geriatric characteristics. This study investigates the relationship between these phenotypes and decisions to limit LST in the ICU. This study is a post hoc analysis of the prospective observational VIP2 study in patients aged 80 years or older admitted to ICUs in 22 countries. The VIP2 study documented demographic, acute and geriatric characteristics as well as organ support and decisions to limit LST in the ICU. Phenotypes were identified by clustering analysis of admission characteristics. Patients who were assigned to one of seven phenotypes (n = 1268) were analysed with regard to limitations of LST. The incidence of decisions to withhold or withdraw LST was 26.5% and 8.1%, respectively. The two phenotypes describing patients with prominent geriatric features and a phenotype representing the oldest old patients with low severity of the critical condition had the largest odds for withholding decisions. The discriminatory performance of logistic regression models in predicting limitations of LST after admission to the ICU was the best after combining phenotype, ventilatory support and country as independent variables. Clinical phenotypes on ICU admission predict limitations of LST in the context of cultural norms (country). These findings can guide further research into biases and preferences involved in the decision-making about LST. Trial registration Clinical Trials NCT03370692 registered on 12 December 2017.


Real-world comparative effectiveness of shockwave lithotripsy versus ureterorenoscopy for the treatment of urinary stones.
To identify clinical and non-clinical predictors of treatment failure and perioperative complications following ureterorenoscopy versus shockwave lithotripsy. The New York State Department of Health Statewide Planning and Research Cooperative System (SPARCS) database was used to identify 226,331 patients who underwent index ureteroscopy or shockwave lithotripsy for renal stones from 2000 to 2016. Propensity-matched generalized linear-mixed modeling was utilized to compare failure and complication rates between the two procedure groups. 219,383 individuals meeting inclusion criteria who underwent either ureterorenoscopy (n = 124,342) or shockwave lithotripsy (n = 95,041) in New York State between 2000 and 2016 were included in our analysis. After propensity score matching, patients undergoing shockwave lithotripsy were found to have decreased odds of experiencing any type of 30-day complication (P < 0.001 for all) but increased odds of treatment failure at both 90 (OR 1.70, 95% CI 1.64-1.77) and 180 (OR 1.83, 95% CI 1.76-1.89) days (P < 0.001 for both). Patients undergoing shockwave lithotripsy experienced significantly higher odds of treatment failure, although this undesirable outcome appears to be partially offset by lower 30-day complication rates.


Four new species of Anenterotrema Stunkard, 1938 (Digenea: Dicrocoellidae) infecting phyllostomid bats in the Peruvian Amazon.
During a research of digeneans (Platyhelminthes: Trematoda) infecting leaf-nosed bats (Chiroptera: Phyllostomidae) from the Kawsay Biological Station in Madre de Dios, southeastern Peru, four new species were described based on light and scanning electron microscopy (SEM): Anenterotrema paramegacetabulum n. sp. from the seba's short-tailed bat Carollia perspicillata Linnaeus, A. hastati n. sp., A. kawsayense n. sp., and A. peruense n. sp. from the greater spear-nosed bat Phyllostomus hastatus (Pallas). Anenterotrema paramegacetabulum n. sp. differs from all congeners by having a terminal oral sucker, a transversely elongated ventral sucker without clamp-shaped, and by having the testes located immediately posterior to ventral sucker. Anenterotrema hastati n. sp. is easily differentiated from the other congeneric species by having an almost clamp-shaped oral sucker, well-developed cirrus sac, a bilobulated seminal receptacle, and a group of well-developed unicellular glands located anterolateral to cirrus sac. Anenterotrema kawsayense n. sp. is characterized by possessing protuberances on the anterior margin of the oral sucker. Anenterotrema peruense n. sp. is mainly characterized by having the testes located principally anterior to ventral sucker and the cirrus sac located perpendicular to midline of the body. The present finding brings to 12, the number of known species of Anenterotrema. A key to the species of Anenterotrema Stunkard, 1938 is provided.


Association between age, sex and cervical and upper cervical rotation tests. Descriptive and correlational study in healthy volunteers.
Active cervical spine rotation (ACROM Rot) shows cervical rotation and flexion rotation test (FRT); side-bending rotation test (SBRT) and upper cervical axial rotation test (C0-C2ART) are described to measure upper cervical rotation. The objectives of this study are (1) to describe the normal range of motion (ROM) of ACROM Rot, and the ROM in FRT, SBRT and C0-C2ART tests; (2) to explore the correlation among the four tests and (3) to investigate the influence of age and sex in their ROM. A cross-sectional study was carried out with healthy volunteers from 18 to 75 years of age. Tests were measured using a CROM device and a bubble inclinometer. Descriptive analysis was performed to establish normative data for the ROM tests. Correlation analysis was conducted to understand the relation between upper and global cervical rotation ROM and among the three upper cervical rotation tests. Linear regression models were developed to understand the influence of age and sex in the ROM of all tests. Normative values were obtained from 122 healthy volunteers (50% male), by sex and age strata. The degree of correlation ranged between 0.582 (p < 0.01) for FRT and ACROM Rot left and 0.217 (p < 0.05) for SBRT and C0-C2ART left. Linear regression models showed the influence of sex for ACROM Rot right (men -4.64° less than women), SBRT (men -4.1° less than women) left and C0-C2ART right and left (men -2.24° and -1.78° less than women). The age influenced rotation ROM with a decrease for every 10 years of -2.11° and -1.96° for ACROM Rot right and left, of -1.72° and -1.26° for FRT right and left and -0.58° and -0.41° for C0-C2ART right and left in the linear regression models. No association was found between age and SBRT (p = 0.63 for right SBRT and p = 0.49 for left SBRT). Weak-to-moderate correlation was found between the upper cervical spine rotation tests and with the ACROM. Women had a larger ROM in ACROM Rot right, SBRT left and C0-C2ART. Decreases in ROM related with age were observed for ACROM Rot, FRT and C0-C2ART but not for SBRT.


Electrical stimulation accelerates neuromuscular junction formation through ADAM19/neuregulin/ErbB signaling in vitro.
The mechanism by which electrical stimulation affects formation of neuromuscular junctions (NMJs) remains unknown. NG108-15, a neural cell line, is commonly used in in vitro co-culture models of myotubes to observe synapse formation; therefore, we employed this model to observe the effects of electrical stimulation on NMJ formation. Initially, L6 cells were differentiated and NG108-15 cells were then added to the same culture dish. After 2 and 3 days of co-culture, the cells were electrically stimulated at 50 V and 0.5 Hz for 0, 5, 30, and 60 min (C, ES5, ES30, and ES60 groups, respectively) and were analyzed after co-culture for 4 days. Immunofluorescence experiments showed significantly increased aggregation of acetylcholine receptors and inhibition of neural outgrowth in the ES30 and ES60 groups. Furthermore, ADAM19 and phospho-ErbB3 were found to be specifically localized in co-cultured NG108-15 cells. Immunoblotting demonstrated that synapsin 1, ADAM19 precursor and its activated form, phospho-ErbB3, and ERK1 protein levels had increased in an electrical stimulation period-dependent manner. Thus, we found that electrical stimulation accelerated NMJ formation, possibly through activation of ADAM19/neuregulin/ErbB signaling in NG108-15 cells.


Detangling the mechanisms and timing of MHC-dependent sexual selection using Soay sheep.
Immune defence is a key component of fitness, and individuals are expected to have evolved preferences for mates that ensure immunocompetent offspring. Potential preferences include those for mates with specific heritable immune gene profiles ("good genes") or for immunogenetically dissimilar mates to increase offspring immune gene diversity. The major histocompatibility complex (MHC) is by far the most investigated immune gene in mate choice studies, but we still know very little about its role in sexual selection for genetic benefits. In this issue of Molecular Ecology, Huang et al. capitalize on the extraordinary wealth of behavioural, life history and genetic/genomic data from the free-living Soay sheep population on the Island of Hirta to address this problem. While the authors find evidence of both pre- and postcopulatory MHC-based sexual selection, postcopulatory MHC-dissimilar mate choice is indistinguishable from genome-wide effects, suggesting it is a byproduct of inbreeding avoidance in Soay sheep. The study's comprehensive sampling ensures that inferences are generalizable to the entire population and provides a gold standard for studies investigating immune gene-based sexual selection.


The Evolution of Transforaminal Endoscopic Spine Surgery.
Transforaminal endoscopic spine surgery (T-ESS) has become a well-accepted technique. The first attempts at percutaneous discectomy by Kambin and Hijikata opened a new chapter of endoscopic spine surgery. By the last quarter of the twentieth century, spine surgeons had begun to adopt this novel technique. Many researchers helped advance endoscopic spine surgery, but the turning point was the description of a safe transforaminal triangle of safety by Parviz Kambin. Since then, the indications for T-ESS have increased as a result of the description of different surgical approaches such as inside-out, outside-in, and half-and-half. We present a review of crucial historical advancements in T-ESS and also discuss the evolution of endoscopes, the techniques used, development of endoscopic instruments and equipment, transforaminal thoracic endoscopy, transforaminal endoscopic interbody fusions, the growth of extended indications, and the future direction of T-ESS. This review provides a detailed description of key historical moments and a bird's-eye view of the vast scope of T-ESS.


Low-dose dental irradiation decreases oxidative stress in osteoblastic MC3T3-E1 cells without any changes in cell viability, cellular proliferation and cellular apoptosis.
Cellular responses following low-dose irradiation have been widely debated. Several studies have revealed detrimental effects of low-dose irradiation; however, some studies have shown contrasting results. Moreover, the effects of periapical irradiation on osteoblastic cells have not yet been revealed. Therefore, in this study, we tested the hypothesis that low-dose dental irradiation of osteoblastic cells reduces reactive oxygen species (ROS) production and leads to increased cellular proliferation and high-dose dental irradiation of osteoblastic cells increases ROS production and leads to cellular apoptosis. We irradiated MC3T3-E1 cells with various doses of periapical irradiation (0, 1, 2, 5 and 10 doses, 1.5 mGy/dose). We evaluated cell viability using MTT assay, the expression of Bax and Bcl-2, as markers for apoptosis and the expression of cyclin D1 as a marker for cell proliferation 24h after each irradiation. We also measured ROS production 4h following each irradiation. ROS production was significantly reduced after one dose of periapical irradiation (1.5 mGy); however, after 10 doses (15 mGy), ROS production was significantly increased (p<0.05). None of the doses of dental radiation affected cell viability as determined by MTT assay, nor did they change the apoptotic marker: (the Bax/Bcl-2 ratio). However, 10 doses of dental irradiation significantly decreased the expression of cyclin D1. Our findings suggest that low-dose dental radiation may help to detoxify osteoblastic cells by reducing ROS production without any changes in cell viability, cellular apoptosis or proliferation. However, high-dose dental radiation impairs osteoblastic proliferation via increase ROS production without any changes in cell viability or apoptotic responses.


Heart Rate Variability in Children With Autism Spectrum Disorder and Associations With Medication and Symptom Severity.
Decreased heart rate variability (HRV) is considered a common marker of autonomic dysfunction that contributes to poor health outcomes. While some studies have suggested that children with autism spectrum disorder (ASD) show reduced HRV, research is yet to consider whether this may be associated with medication use and symptom severity. This study examined the relationship between resting state HRV, medication use and symptom severity in children diagnosed with ASD. Children with ASD (N = 86), aged between 3 and 12 years (M = 8.09), were compared to 44 neurotypical children of similar age (M = 7.15). Laboratory assessment of HRV involved 5 min of non-invasive baseline electrocardiogram assessments while participants viewed an age-appropriate non-verbal animated video. Time-domain and frequency-domain HRV measures were analyzed. ASD symptom severity was assessed using the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) and Social Responsiveness Scale (SRS-2). Results indicated that children with ASD exhibited reduced resting HRV relative to neurotypical children. Subsequent analyses within the ASD group suggested that this group difference was greater in children who were taking psychotropic medication (N = 36). Our data also provides tentative evidence of a relationship between HRV and social impairment symptoms in children with ASD, with more severe repetitive behaviors (as measured by the ADOS-2) associated with decreased resting HRV. Overall, these findings suggest that HRV may be atypical in children with ASD and suggest the importance of exploring HRV as a risk factor for cardiovascular health in this group. LAY SUMMARY: Cardiac activity, such as heart rate variability (HRV), can provide insight into the autonomic nervous system. This study reports on the association between resting-state HRV and autonomic nervous system activity in young children with autism spectrum disorder (ASD) compared to neurotypical children. These results may help us understand what underlies autonomic nervous system dysfunction and the potential pathophysiological mechanisms leading to increased cardiovascular risk in ASD.


RNAi and RNAa--the yin and yang of RNAome.
RNA interference (RNAi) is a powerful technology with huge applications for functional genomics, target identification in drug discovery and elucidation of molecular signaling pathways. Current RNAi studies have demonstrated the clinical potential of small interfering RNAs (siRNAs) in metabolic diseases, cancer, AIDS, malaria, neurodegenerative disorders, dental diseases and other illnesses. Interestingly, recent studies have shown that the small RNA molecules, either indigenously produced as microRNAs (miRNAs) or exogenously administered synthetic dsRNAs could effectively activate a particular gene in a sequence specific manner instead of silencing it. This novel, but still uncharacterized, phenomenon has been termed as RNA activation (RNAa). The paradoxical concept of Yin and Yang, which describe two primal opposing but complementary principles, can potentially be applied to elucidate the complex phenomenon of RNAa/RNAi in the RNAome. This warrants a proper understanding of the RNAi/RNAa molecular pathways in living organisms before any of the small dsRNAs can potentially be exploited for therapeutics in human beings.


Dynamics of base pairs with low stability in RNA by solid-state nuclear magnetic resonance exchange spectroscopy.
Base pairs are fundamental building blocks of RNA. The base pairs of low stability are often critical in RNA functions. Here, we develop a solid-state NMR-based water-RNA exchange spectroscopy (WaterREXSY) to characterize RNA in solid. The approach uses different chemical exchange rates between iminos and water to evaluate base pair stability; the less stable ones would exchange more frequently, leading to stronger cross-peaks on WaterREXSY. Applied to the riboA71-adenine complex (the 71nt-aptamer domain of add adenine riboswitch from Vibrio vulnificus), the U47⋅U51 base pair, which is critical in ligand binding, was found to be less stable than other base pairs. The imino-water exchange rates of U47 at different temperatures are about 500-800 s-1, indeed indicative of low stability. This implies a highly complex and plastic triad involving U47⋅U51 and that the opening of the U47⋅U51 base pair may be the early stage of ligand release.


Implementation Science for closing the treatment gap for mental disorders by translating evidence base into practice: experiences from the PRIME project.
This paper utilizes the experience of PRIME (Programme for Improving Mental health care) to exemplify how implementation science provides key insights and approaches to closing the treatment gap for mental disorders. The real-world application of strategies described in the implementation science literature, accompanied by use of alternative, rigorous evaluation methods to assess their impact on patient outcomes, can help in closing the mental health treatment gap in disadvantaged populations.


Abnormal distribution of hippocampal mossy fibers in rats exposed to X-irradiation in utero.
The effects of prenatal X-irradiation (0.3, 0.6, 1.2 or 1.8 Gy) on the hippocampal development were examined at six weeks of age in rats. The laminar structure of the hippocampus was deranged in the rats exposed to 0.6 Gy or more. Pyramidal cells in the CA-3 region were more susceptible than those in the CA-1 region. Aberrant mossy fiber terminals were observed in the stratum oriens of the CA-3 region (infrapyramidal mossy fibers) in rats exposed to 0.3 Gy or more.


Improved performance of enzyme-linked immunosorbent assays and the effect of human immunodeficiency virus coinfection on the serologic detection of herpes simplex virus type 2 in Rakai, Uganda.
Ugandan subjects (820) were tested by Focus HerpeSelect enzyme-linked immunosorbent assay (ELISA), Kalon herpes simplex virus type 2 ELISA, and BioKit rapid test, and the results were compared to those of Western blotting. Higher-than-standard-index cutoff values gave optimal sensitivity and specificity. Kalon ELISA was the optimal assay when an index value of 1.5 was used (sensitivity, 91.7%; specificity, 92.4%).


Detection and analysis of protofibrils and fibrils of hemoglobin: implications for the pathogenesis and cure of heme loss related maladies.
TFE induces structural alterations of proteins similar to the lipid environment of biological membranes, implicating these studies worthy of analyzing protein conformation in membranes such as red blood cells (RBCs). Heme loss occurs on rupturing of RBCs as found in diseases namely haemophilia, haemolytic anaemia, diabetes mellitus. TFE can be implied in discovering therapeutic targets, as it mimics the biological membrane environment. A global transition of hemoglobin (Hb) in presence of TFE was studied by using multi-methodological approach. The presence of partially folded state of Hb at 15% v/v TFE was confirmed by altered tryptophan environment, and retention of native-like secondary and tertiary structure. Molten globule state was observed at 20% v/v TFE as detected by increase tryptophan and high ANS fluorescence, slight alterations in Soret band relative to native. TFE on increasing concentration induced protofibrils at 25% v/v and fibrils at 45% v/v as depicted by altered tryptophan environment, heme loss, increase in non-native β-sheet secondary and tertiary structure, large hydrodynamic radii of heme-protein, high ANS, thioflavin T fluorescence and shift in Congo Red absorbance. Comet assay showed that protofibrils are cytotoxic to lymphocytes. SEM and XRD confirmed these aggregates to be fibrillar in nature.


Do pregnant women and those at risk of developing post-natal depression consume lower amounts of long chain omega-3 polyunsaturated fatty acids?
The aims were to compare intakes of long chain omega-3 polyunsaturated fatty acid (LC n-3 PUFA) in pregnant and non-pregnant women in Australia and to compare these intakes to the Australian National Nutrition Survey of 1995 (NNS95) [1] and to determine if the LC n-3 PUFA intakes differed in women who may be 'at risk' compared with women 'not at risk' of developing post-natal depression (PND). A validated LC n-3 PUFA food frequency questionnaire and pregnant women's Edinburgh Postnatal Depression Scale (EPDS) scores were used. LC n-3 PUFA intakes were comparable to the NNS95 but did not differ due to pregnancy or whether or not a woman is at risk of developing PND.


Development of bespoke hardware and software to enable testing of a novel method of managing the charge and discharge of series-connected battery packs.
The novel feature of the method of battery management under development and testing is that routine balancing of the cells is eliminated throughout the service life of the battery pack. This requires preparation of the battery cells and configuration of the rigs in such a way as to ensure that the cells are accurately balanced on assembly and that thereafter there is no cell-to-cell variation in charge current or load at any time, measured to a low microamp level. In addition, the method requires a special charge control algorithm which was devised in order to accommodate cell-to-cell variations in capacity and dynamic response. Comprehensive experimental testing of this method, which is fully described in the associated paper (Hardy et al., 2023), required the development of hardware and software which would combine the necessary functions of a battery test rig and a battery management system capable of carrying out the special method of charge control described below. These included:•The automated control of contactors, loads and chargers to perform multiple charge/discharge cycles to predetermined patterns of current and maximum and minimum cell voltages.•Monitoring of cell voltages, current and temperature and the provision of test and diagnostic data.•Performing the safety functions of a Battery Management System to ensure that no cell was permitted to exceed limitations of current, voltage or temperature. The hardware and software were developed through three phases of testing with the operational principles (but not all the hardware and software elements) carrying over from one phase to the next.


Association between dairy intake and risk of incident dementia: the Ohsaki Cohort 2006 Study.
To investigate the association between dairy intake and risk of incident dementia in older adults. A longitudinal analysis of dairy intake with incident dementia was conducted using a cohort study of 11,637 non-disabled Japanese older adults aged ≥ 65 years followed-up for up to 5.7 years (mean: 5.0 years). Data on milk, yogurt, and cheese intake were collected using a validated food frequency questionnaire. Total dairy intake was calculated as the sum of the daily intake of milk, yogurt, and cheese, which was sex-specifically categorized in quintiles. Dementia cases were retrieved from the public long-term care insurance database. Cox proportional hazards model was used to estimate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incident dementia. During 58,013 person-years of follow-up, 946 persons developed dementia. In the primary analysis, compare to the lowest quintile of total dairy intake, Q2 showed a slightly decreased incident dementia risk (HR for Q2 vs Q1: 0.90, 95% CI: 0.73-1.10) after fully adjusted for demographic, lifestyle, psychological, and nutritional factors, and diseases history. Compared to non-consumers of milk, those consuming for 1-2 times/month showed a lower risk of incident dementia (fully-adjusted HR: 0.76, 95% CI: 0.57-1.02). Daily yogurt consumers also had a reduced risk (fully-adjusted HR: 0.89, 95% CI: 0.74-1.09). But daily cheese consumers showed an increased risk of dementia (fully-adjusted HR: 1.28, 95% CI: 0.91-1.79). In the sensitivity analysis where we excluded dementia cases ascertained in the first 2 years, results were consistent with those from the primary analysis and we further found that yogurt intake might be inversely associated with dementia risk (p for trend = 0.025). Low total dairy intake or low milk intake frequency might be associated with lower incident dementia risk, however daily cheese consumers seemed to have an increased risk. Our study also suggested a possible inverse dose-response association between yogurt consumption and dementia risk, but further studies are needed to confirm whether this benefit was from yogurt intake itself or as a part of a healthy dietary pattern.


Competition for Gβγ dimers mediates a specific cross-talk between stimulatory and inhibitory G protein α subunits of the adenylyl cyclase in cardiomyocytes.
Heterotrimeric G proteins are key regulators of signaling pathways in mammalian cells. Beyond G protein-coupled receptors, the amount and mutual ratio of specific G protein α, β, and γ subunits determine the G protein signaling. However, little is known about mechanisms that regulate the concentration and composition of G protein subunits at the plasma membrane. Here, we show a novel cross-talk between stimulatory and inhibitory G protein α subunits (Gα) that is mediated by G protein βγ dimers and controls the abundance of specific Gα subunits at the plasma membrane. Firstly, we observed in heart tissue from constitutively Gαi2- and Gαi3-deficient mice that the loss of Gαi2 and Gαi3 was accompanied by a slight increase in the protein content of the nontargeted Gαi isoform. Therefore, we analyzed whether overexpression of selected Gα subunits conversely impairs endogenous G protein α and β subunit levels in cardiomyocytes. Integration of overexpressed Gαi2 subunits into heterotrimeric G proteins was verified by co-immunoprecipitation. Adenoviral expression of increasing amounts of Gαi2 led to a reduction of Gαi3 (up to 90 %) and Gαs (up to 75 %) protein levels. Likewise, increasing amounts of adenovirally expressed Gαs resulted in a linear 75 % decrease in both Gαi2 and Gαi3 protein levels. In contrast, overexpression of either Gαi or Gαs isoform did not influence the amount of Gαo and Gαq, both of which are not involved in the regulation of adenylyl cyclase activity. The mRNA expression of the disappearing endogenous Gα subunits was not affected, indicating a posttranslational mechanism. Interestingly, the amount of endogenous G protein βγ dimers was not altered by any Gα overexpression. However, the increase of Gβγ level by adenoviral expression prevented the loss of endogenous Gαs and Gαi3 in Gαi2 overexpressing cardiomyocytes. Thus, our results provide evidence for a novel mechanism cross-regulating adenylyl cyclase-modulating Gαi isoforms and Gαs proteins. The Gα subunits apparently compete for a limited amount of Gβγ dimers, which are required for G protein heterotrimer formation at the plasma membrane.


Upper tract management when posterior urethral valve ablation is insufficient.
Of 105 boys with posterior urethral valves managed during a 10-year period most were managed by primary valve ablation. However, 39 of these boys required concomitant or additional procedures to 71 massively dilated ureters because of azotemia, infection and/or progressive upper tract deterioration. In 17 boys 25 ureters could be reconstructed primarily by varying degrees of ureteral tailoring. When there was severe infection, azotemia and/or doubt as to the function of the affected renal unit, staged reconstruction was initiated by cutaneous ureterostomy. One-fourth of these ureterostomy diverted children died of azotemia despite free urinary drainage. Those who went on to have staged reconstruction, despite multiple surgical procedures, retained intact urinary systems with acceptable function.


Inaccuracy of self-reported low sodium diet.
This study evaluates how often the self-report of a low sodium (Na) intake is reflected by a low 24-h urinary sodium excretion and examines the influence of incomplete urinary collections on this comparison. In a study in which 24-h urine collections were obtained for measurement of Na and creatinine excretion, 120 participants were asked whether their Na intake was low, medium, or high. A 24-h urine collection was considered complete if creatinine excretion was ≥20 mg/kg in men or ≥15 mg/kg in women, and incomplete if below those amounts. The kappa statistic was computed to assess the level of agreement between 24-h Na excretion, dichotomized at 100 meq and self-report responses. Agreement between self-reported and actual Na excretion was poor. The kappa statistic was 0.18 for the total sample, 0.04 for complete collectors, and 0.51 for incomplete collectors, respectively. Overall, 24-h Na excretion exceeded 100 meq among 75% of those reporting an average or high Na intake, but it also exceeded 100 meq among 57% of those reporting a low sodium intake. Further, among those reporting a low sodium intake, Na excretion exceeded 100 meq in 80% of those who submitted a complete collection, but in only 29% of those who submitted an incomplete collection. These findings suggest that many individuals who report a low salt diet actually excrete ≥100 meq/day. Na intake is also frequently underestimated because many 24-h urine collections are incomplete.


Some biochemical characteristics of L1210 cell lines resistant to 6-mercaptopurine and 6-thioguanine and with increased sensitivity to methotrexate.
L1210 cells resistant to 6MP and 6TG exhibit increased sensitivity to MTX compared to the parent line. The differential response of parent and purine analog-resistant cell lines to MTX is not due to host influences, for both L1210/6MP and L1210/6TG cell lines are cross-resistant to 6-MeMPR, an inhibitor of de novo synthesis, and cultured L1210/6MP cells are more sensitive to MTX than the parent cell line. Following treatment of tumor-bearing mice with MTX, the drug concentration in L1210/6TG cells was about 50% greater than in L1210/0 cells for 24 hr and may account, wholly or in part, for the increased sensitivity of the L1210/6TG cell line to MTX. L1210/6MP cells, however, accumulated less MTX than L1210/0 cells, indicating that an equivalent mechanism is not operative in these cells. DHFR activity in L1210/6TG cells was the same as that in L1210/0 cells, but activity in L1210/6MP cells was lower by 60%. Cultured L1210/6MP cells also exhibited a deficiency in DHFR activity as compared to the parent cell line. The sensitivity of the enzyme to MTX was the same for all three cell lines propagated in vivo. Therefore, the increased sensitivity of the L1210/6MP cell line to MTX may be due, in part, to decreased DHFR activity. Significantly lower levels of GTP + GDP and CTP in 6TG-resistant cells than in parent cells 4 hr after the administration of MTX to tumor-bearing mice may be related to the increased MTX sensitivity of these cells. Our results indicate that the observed alterations in drug sensitivity are associated with more than one biochemical change and that these changes are different in the two purine analog-resistant cell lines.


Metabotropic receptors for ATP and UTP: exploring the correspondence between native and recombinant nucleotide receptors.
In the past five years, an extended series (P2Y1-n) of metabotropic nucleotide (P2) receptors has been cloned from vertebrate tissues; these receptors are activated by either ATP or UTP, or both nucleotides. While certain cloned P2Y receptors appear to correspond functionally to particular native P2 receptor phenotypes, such pharmacological phenotypes could be explained by either a combination of several members of the P2Y1-n series being coexpressed in the same tissue or the existence of novel, uncloned P2Y subtypes. Here, Brian King, Andrea Townsend-Nicholson and Geoffrey Burnstock review recent findings on the matter of pharmacological relationships between native P2 and cloned P2Y receptors.


A single-center experience on exchange transfusion therapy in 123 full-term cases of severe neonatal hyperbilirubinemia in Wuhan.
To describe the clinical experience in application of exchange transfusion therapy (ETT) in the treatment of severe neonatal hyperbilirubinemia. The clinical data and examination results of severe neonatal hyperbilirubinemia full-term cases treated by ETT were analyzed retrospectively, the etiology and risk factors of severe neonatal hyperbilirubinemia were statistically analyzed, and the statistical characteristics of the children in each etiological group and the incidence of adverse events of ETT were analyzed. The age of jaundice, peak total bilirubin after phototherapy and ETT in 123 full-term infants were 2.0 (1.0, 3.0) days, 4.0 (2.0, 7.0) days and 4.0 (2.0, 7.0) days, respectively, of which 68 were male and 55 were female. The main pathogeny of severe neonatal hyperbilirubinemia was blood group incompatibility hemolytic disease of newborn (HDN). Age of ETT, total bilirubin after ETT, gender and BAEP results were different between ABE and non-ABE infants. Weight loss can be used as a predictor of hospitalization length. The major adverse events related to ETT were hypocalcemia, hypomagnesemia, hyponatremia and thrombocytopenia. ETT can rapidly reduce the level of total bilirubin to prevent ABE and play an important role in the treatment of neonatal hyperbilirubinemia, but the whole process of ETT needs to be closely monitored.


Effects of sodium-glucose cotransporter 2 inhibitors on hypoglycaemia in brittle diabetic patients with decreased endogenous insulin secretion.
The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2Is) on fasting blood glucose concentration (FBG) in patients with unstable FBG despite undergoing intensive insulin therapy (IIT) remain unclear. This study aimed to identify the effects of SGLT2Is on unstable FBGs. Thirty brittle diabetic patients with unstable FBGs despite undergoing IIT were included in the study. SGLT2Is were added and used in combination. We evaluated the data of the subjects in Evaluation 1 (immediately before using SGLT2Is) and evaluations 2, 3 and 4 (4, 24 and 48 weeks after starting concomitant therapy, respectively). FBGs were measured every day for a period of 28 days immediately before conducting Evaluations 1, 2, 3 and 4. The mean value of the 28 sets of FBG data (FBG mean) and their standard deviation (SD) values were established as each evaluation's FBGs. The changes in the mean values of the 30 subjects as well as their SD before and after concomitant therapy were evaluated. The concomitant use of SGLT2Is helped reduce not only FBG mean but also SD. FBG max dropped, and the frequency of occurrence of hyperglycaemic FBG (>11.1 mmol/L) decreased. However, FBG min did not drop, and the frequency of occurrence of hypoglycaemic FBG (<3.9 mmol/L) increased. The frequency of occurrence of subjective hypoglycaemia decreased. The decrease in the SD of FBG was related to the decrease in subjective hypoglycaemia. Concomitant use of SGLT2Is in patients with brittle diabetes appears to be useful in terms of improvement of FBG and fewer occurrences of hypoglycaemic events.


Positive associations between cannabis and alcohol use polygenic risk scores and phenotypic opioid misuse among African-Americans.
This study examined whether polygenic risk scores (PRS) for lifetime cannabis and alcohol use were associated with misusing opioids, and whether sex differences existed in these relations in an urban, African-American sample. Data were drawn from three cohorts of participants (N = 1,103; 45% male) who were recruited in first grade as part of a series of elementary school-based, universal preventive intervention trials conducted in a Mid-Atlantic region of the U.S. In young adulthood, participants provided a DNA sample and reported on whether they had used heroin or misused prescription opioids in their lifetime. Three substance use PRS were computed based on prior GWAS: lifetime cannabis use from Pasman et al. (2018), heavy drinking indexed via maximum number of drinks from Gelernter et al. (2019), and alcohol consumption from Kranzler et al. (2019). Higher PRS for lifetime cannabis use, greater heavy drinking, and greater alcohol consumption were associated with heightened risk for misusing opioids among the whole sample. Significant sex by PRS interactions were also observed such that higher PRS for heavy drinking and alcohol consumption were associated with a greater likelihood of opioid misuse among males, but not females. Our findings further elucidate the genetic contributions to misusing opioids by showing that the genetics of cannabis and alcohol consumption are associated with lifetime opioid misuse among young adults, though replication of our findings is needed.


Aluminum uptake and migration from the soil compartment into Betula pendula for two different environments: a polluted and environmentally protected area of Poland.
This paper presents the impact of soil contamination on aluminum (Al) concentrations in plant parts of Betula pendula and a possible way of migration and transformation of Al in the soil-root-stem-twig-leaf system. A new procedure of Al fractionation based on extraction in water phase was applied to obtain and measure the most available forms of Al in soils and B. pendula samples. In addition, total Al content was determined in biological samples and pseudo total Al content in soil samples collected under plant saplings, using atomic absorption spectrometry with flame atomization. A number of relations concerning the occurrence of Al and Ca in soils and plant parts of B. pendula (tap roots, lateral roots, stem, twigs, and leaves) were observed. Based on the research findings, the mechanism of Al migration from soil to the leaves of B. pendula can be presented. It was found that aluminum uptake may be limited in roots by high calcium concentration. The application of a new procedure based on the simple sequential extraction of water-soluble fractions (the most available and exchangeable fractions of Al) can be used as an effective tool for the estimation of aluminum toxicity in soils and plants.


Papillary carcinoma of the thymus gland.
In 1999, the World Health Organization introduced a new classification of a rare thymic cancer called papillary adenocarcinoma of the thymus gland. In this study we report on a case of papillary thymic carcinoma in a 29-year-old woman. Histologically, the tumor consisted of a papillary component admixed with a solid component, a component that is commonly found in type A thymoma.


Coexistence between human and wildlife: the nature, causes and mitigations of human wildlife conflict around Bale Mountains National Park, Southeast Ethiopia.
Human-wildlife conflict occurs when the needs and behavior of wildlife impact negatively on humans or when humans negatively affect the needs of wildlife. To explore the nature, causes and mitigations of human wildlife conflict, the coexistence between human and wildlife assessment was conducted around Bale Mountains National Park. Data were collected by means of household questionnaires, focus group discussion, interview, field observation and secondary sources. The nature and extent of human wildlife conflict in the study area were profoundly impacted humans, wild animal and the environment through crop damage, habitat disturbance and destruction, livestock predation, and killing of wildlife and human. The major causes of conflict manifested that agricultural expansion (30%), human settlement (24%), overgrazing by livestock (14%), deforestation (18%), illegal grass collection (10%) and poaching (4%). To defend crop raider, farmers have been practiced crop guarding (34%), live fencing (26%), scarecrow (22%), chasing (14%), and smoking (5%). However, fencing (38%), chasing (30%), scarecrow (24%) and guarding (8%) were controlling techniques to defend livestock predator animals. As emphasized in this study, human-wildlife conflicts are negative impacts on both human and wildlife. Accordingly, possible mitigate possibilities for peaceful co-existence between human and wildlife should be create awareness and training to the local communities, identifying clear border between the closure area and the land owned by the residents, formulate rules and regulation for performed local communities, equal benefit sharing of the local communities and reduction of human settlement encroachment into the national park range. Generally, researcher recommended that stakeholders and concerned bodies should be creating awareness to local community for the use of wildlife and human-wildlife conflict mitigation strategies.


Pancreatic cancer drug-sensitivity predicted by synergy of p53-Activator Wnt Inhibitor-2 (PAWI-2) and protein biomarker expression.
Today, pancreatic cancer (PC) is a major health problem in the United States. It remains a challenge to develop efficacious clinically useful PC therapies. New avenues, based on translational approaches and innovative validated biomarkers could be a preclinical option to evaluate PC drug candidates or drug combinations before clinical trials. Herein, we describe evaluation of combination therapies by incorporating a novel pathway modulator, p53-Activator Wnt Inhibitor-2 (PAWI-2) with other FDA-approved cancer drugs that have been used in PC clinical trials. PAWI-2 is a potent inhibitor of drug-resistant PC cells that has been shown to selectively ameliorate human pancreatic cancer stem cells (i.e., hPCSCs, FGβ3 cells). In the present study, we showed PAWI-2 produced therapeutic synergism with certain types of anti-cancer drugs. These drugs themselves oftentimes do not ameliorate PC cells (especially PCSCs) due to high levels of drug-resistance. PAWI-2 has the ability to rescue the potency of drugs (i.e., erlotinib, trametinib) and inhibit PC cell growth. Key molecular regulators of PAWI-2 could be used to predict synergistic/antagonistic effects between PAWI-2 and other anti-cancer drugs. Anti-cancer results showed potency could be quite accurately correlated to phosphorylation of optineurin (OPTN) in PC cells. Synergism/antagonism was also associated with inhibition of PCSC marker SOX2 that was observed in FGβ3 cells. Synergism broadens the potential use of PAWI-2 as an adjunct chemotherapy in patients with PC that have developed resistance to first-line targeted therapies or chemotherapies.


Potential role of hematopoietic stem cell transplantation in children with secondary acute lymphocytic leukemia.
Secondary acute lymphocytic leukemias (ALL) are uncommon events in the pediatric patient population. There are few detailed reports on the laboratory characteristics and clinical course of patients with secondary lymphocytic leukemia. Historically, these patients have had a poor outcome. We report two patients treated at one institution who developed treatment-related secondary ALL. Both patients underwent hematopoietic stem cell transplantation, one with a compatible unrelated donor cord blood unit and one with an HLA-matched sibling donor bone marrow. One of the two patients survives disease-free 3 years after transplantation.


Pathogenic "germline" variants associated with myeloproliferative disorders in apparently normal individuals: Inherited or acquired genetic alterations?
Myeloproliferative syndromes (MPS) are hematologic malignancies due to the expansion of an abnormal hematopoietic stem cell. They include chronic myeloid leukemia (CML) and non-CML MPS such as polycythemia vera, essential thrombocythemia and primary myelofibrosis. The latter are distinguished by somatic pathogenic variants affecting JAK2, CALR, or MPL genes. Apparent germline pathogenic variants have been reported in the general population. Here, we found that two gnomAD data-sets report more homozygotes than expected for the JAK2 c.1849G > T(Val617Phe) variant. We propose that somatic gene conversion can explain the presence of those unexpected homozygotes in normal populations. Consistently, homozygous individuals are older than 65 years. We also found a lower-than-expected frequency of the JAK2 variant in younger individuals suggesting that somatic mutation can underlie its presence in (at least some) heterozygotes. Regarding pathogenic variants in MPL and CALR, they are also present in the gnomAD data-sets explored. However, we cannot conclude that such seemingly germline variants are in fact somatic alterations. These results suggest that apparently normal individuals bearing MPS-related variants can be subclinical/undiagnosed MPS cases of somatic origin. It would be interesting to assess the hematologic phenotype of such individuals and the presence of the relevant variants in other tissues.


Ventricular fibrillation associated with early repolarization in a patient with thyroid storm.
We present a case of a 69-year-old male who was hospitalized for the treatment of thyroid storm due to Grave's disease, who presented with unexpected ventricular fibrillation (VF). The possible etiology was early repolarization (ER), characterized by J-point elevation in inferior and posterolateral leads, unmasked by the attenuation of beta-adrenergic effect with normalization of thyroid hormones and following the administration of a beta-blocker. Our case focuses attention on the occurrence of VF in a patient with ER during the treatment of hyperthyroidism, which to our knowledge is the first such report.


Distinct Prognosis of Minimal Residual Disease According to Breast Cancer Subtype in Patients with Breast or Nodal Pathologic Complete Response After Neoadjuvant Chemotherapy.
Few studies have reported on patient prognosis according to residual cancer burden after neoadjuvant chemotherapy (NAC). Herein, we evaluated the survival of patients based on residual disease after NAC to identify subpopulations with distinct prognoses. We retrospectively reviewed 728 patients treated with NAC from 2010 to 2017. Patients were divided into four subgroups depending on post-surgical residual disease according to the staging system: pathological complete response (pCR) (ypT0/TisN0), minimal residual disease (MRD) (ypT1mi/T1aN0 or ypT0/Tis ypN0i+/N1mic), node-only pCR (≥ ypT1b ypN0), and breast-only pCR (ypT0/Tis ≥ ypN1a). Clinicopathological characteristics and survival outcomes were analyzed by adjusting for factors affecting survival. Overall, 50.4% (n = 367) of patients achieved pCR, with the MRD group accounting for 16.5% (n = 120). Although age and clinical stage were not different among the study groups, histologic grade, subtypes, chemotherapy response, and local treatment showed differences. Event-free survival (EFS) and overall survival (OS) demonstrated no significant difference between the pCR and MRD groups. In the multivariate analysis, pCR status was the only significant factor in EFS, and no statistical difference was noted between the pCR and MRD groups. However, clinical stage, pCR status, and subtype significantly affected the OS. MRD showed favorable outcomes in terms of both EFS and OS in all subtypes, except for those with triple-negative breast cancer (TNBC). Patients with MRD showed outcomes comparable to those of patients who achieved pCR and may be candidates for de-escalation of post-NAC treatment, except for those with a TNBC subtype.


Spotlighting the imbalance: Gender disparities among speakers and awardees at pediatric emergency medicine conferences.
There are wide variations in the gender makeup of speakers at national pediatric emergency medicine (PEM) conferences with no significant change in recent years. Gender disparities exist among national speakers and award recipients. PEM represents the intersection of pediatrics, a female-dominated specialty with approximately 58% women, and emergency medicine, a male-dominated specialty. We describe the proportion of women speakers and award recipients at two national PEM conferences, the American Academy of Pediatrics (AAP) Section on Emergency Medicine (SOEM) and the Advanced PEM Assembly (APEMA), to the AAP National Conference & Exhibition (NCE), a national pediatric conference. Data from SOEM and APEMA, obtained from 2016 to 2021 were compared to the 2021 NCE. Invited speakers, abstract presenters, and award recipients were identified. Gender was determined by searching each individual's name for self-identification. Gender proportions were compared across conferences, speaker type, and year. Compared to the NCE, a significantly smaller proportion of women were invited speakers at APEMA (NCE 59.9% vs. APEMA 38.8%, p < 0.001), but similar proportions of women were invited speakers (53.9%, p = 0.178) and awardees at SOEM (50% vs. 50%, p = 1.0). A larger number of women were SOEM abstract presenters than invited speakers (63.3% vs. 53.9%, p = 0.041). Between 2016 and 2021, the proportion of women invited speakers (SOEM, p = 0.744; APEMA, p = 0.947) or abstract presenters (SOEM, p = 0.632) did not significantly change. Compared to NCE, women are underrepresented as speakers at APEMA, but not at SOEM. Abstract presenters are more likely to be women compared to invited speakers. While awards appear equally distributed, recipients do not mirror the proportion of women in PEM. Conference organizers and leaders in PEM should ensure gender equity in national recognition.


Quantitative evaluation of oral function in acute and recovery phase of idiopathic facial palsy; a preliminary controlled study.
Patients with peripheral facial palsy frequently complain of fluid leakage and food retention during meals. We investigated oral function during eating in adults with peripheral facial palsy. A prospective two-phase controlled observational study. Data were collected at the ENT clinic in Nihon University Itabashi Hospital (patients) and Nihon University Dental Hospital (controls) between September 2009 and August 2011 and analysed at the Department of Oral Diagnostic Sciences in Nihon University School of Dentistry. Fourteen patients with acute idiopathic facial palsy and 14 controls completed Study 1. Sixteen patients with acute idiopathic facial palsy and 16 controls completed Study 2. In Study 1, oral vestibular cleansing capability was assessed by measuring the amount of rice remaining in the oral vestibule after mastication. In Study 2, masticatory efficiency was evaluated by measuring glucose eluted from gummy jelly during chewing. These oral functions were observed at the first visit and final visit (after patients with facial palsy had recovered). Oral vestibular cleansing capability at the first visit was significantly decreased by facial palsy (P < 0.001 versus healthy volunteers and P < 0.001 versus contralateral side) but recovered as facial muscular function improved (P = 0.034). There was a significant correlation between improvement in paralysis and decreased food retention (r = -0.528, P = 0.010). At the first visit, masticatory efficiency on the affected side was significantly lower than that of controls (P = 0.002) but had mostly recovered after resolution of facial palsy (P = 0.033). Oral functions were decreased by peripheral facial palsy. Oral vestibular cleansing capability was more significantly associated than masticatory efficiency with facial muscle function. Our data suggest that peripheral facial palsy impairs eating and worsens oral hygiene, which may result in oral disease.


Dynamic Changes in Fibrinogen and Prognosis of Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis.
This study aimed to investigate the association between dynamic changes in fibrinogen and the prognosis of acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT). We measured fibrinogen levels at admission and 24 h after IVT in 364 consecutively recruited AIS patients. The primary outcome was the composite measure of death or major disability (modified Rankin Scale score 3-6) at 3 months. During the 3-month follow-up, 127 (34.89%) patients experienced death or major disability. After multivariate adjustment, a ≥ 2.5% increase in fibrinogen was associated with an increased risk of the primary outcome (odds ratio [OR], 2.26; 95% confidence interval [CI] 1.08-4.75; p trend = 0.030) when 2 extreme tertiles were compared. Each 1% increase in fibrinogen after IVT was associated with a 1% increase in the risk of the primary outcome (OR 1.01, 95% CI 1.00-1.03). Multivariable-adjusted spline regression revealed a linear dose-response relationship between fibrinogen changes after IVT and the primary outcome (p for linearity = 0.032). The addition of fibrinogen changes to conventional risk factors improved the re-classification (but not discrimination) of the primary outcome (net reclassification index 27.6%, p = 0.011). These findings indicated that an increase in fibrinogen after IVT was associated with an increased risk of death or major disability in AIS patients, suggesting that monitoring the dynamic profile of fibrinogen levels may help neurologists improve stroke outcomes in clinical settings.


Cataract, glaucoma, and diabetic retinopathy are independent risk factors affecting falls in the older adult with eye diseases.
Falls are the leading cause of injury-related hospitalization in older adult, presenting a significant public health concern. To examine the specific eye diseases for risk factors of falls in the older adult. A total of 775 older adults admitted to tertiary care hospitals were divided into a fall or non-fall group based on a questionnaire. Logistic regression analysis was used to identify factors associated with falls. With 208 falls, 775 participants were recruited. The major associated factors of falls were older age (Odds ratios [OR]: 1.05), female (OR: 1.91), cardiovascular diseases (OR: 1.65), more outdoor activities (OR: 2.81), cataract (OR: 1.65), glaucoma (OR: 1.63), diabetic retinopathy (OR: 2.72). Our study demonstrates that cataract, glaucoma, and diabetic retinopathy in the older adult with eye diseases are independent risk factors of falls, which may shed light on the prevention of falls in the older adult with eye diseases.


[Differential diagnosis of the microcalcifications. The calcified mastopathic microcyst (author's transl)].
Coarse plaqued calcifications which were up to now regarded as typical for sclerosing adenosis appear on the lateral films often as sickle- or linear shaped configurations. This pattern - described by the author as "tea-cup-phenomenon" corresponds to the microcyst filled with calcium milk. The sclerosing adenosis cannot be identified with this type of calcification.


Role of protein kinase C and the Na+/H+ antiporter in suppression of apoptosis by granulocyte macrophage colony-stimulating factor and interleukin-3.
Granulocyte macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) suppress apoptosis in hemopoietic cells, a process of active cell death characterized by the degradation of genomic DNA into oligonucleosomic fragments. The present study was therefore initiated with the view that the two growth factors may trigger the same early events in the cell, leading to suppression of apoptosis. We provide evidence here for a role of protein kinase C and of the Na+/H+ antiporter in the signal transduction pathways activated by binding of GM-CSF or IL-3 to their respective receptors, resulting in suppression of apoptosis in target cells. First, kinetic studies indicate that the process is irreversible after two hours of deprivation. The suppression of apoptosis by GM-CSF and IL-3 is dose-dependent, with half-efficient concentrations that are in the range of the dissociation constants of the high affinity GM-CSF or IL-3 receptor, respectively. Second, the use of three inhibitors of protein kinase C (PKC), H7, staurosporine, and sphingosine, in concentrations that are below their toxicity limits, revert the suppression of apoptosis by IL-3 and GM-CSF. Conversely, the use of 12-O-tetradecanoylphorbol-13-acetate (TPA), a PKC activator, allows a bypass of receptor activation in suppression of apoptosis. Western blotting of cytosolic and membrane proteins indicate that exposure of the cells to GM-CSF, IL-3, or TPA results in translocation of PKC to the cell membrane. Our data, therefore, indicate that the activation of PKC is important in suppression of apoptosis by GM-CSF and IL-3. Third, the two amiloride derivatives 5-(N,N-hexamethylene) and 5-(N-ethyl-N-isopropyl)amiloride that specifically block the function of the Na+/H+ antiport also revert the protective effect of GM-CSF, IL-3, and TPA on MO7-E cells. Further, exposure of the cells to GM-CSF, IL-3, or TPA results in sustained pHi alkalinizatio, which is abrogated when the cells are preincubated with 5-(N-ethyl-N-isopropyl)amiloride, a specific inhibitor of the antiport. Preincubation of the cells with staurosporine, a PKC inhibitor, also significantly reduces the effect of GM-CSF or IL-3 on pHi. Taken together, our data indicate that a functional antiport is required in suppression of apoptosis by GM-CSF, IL-3, or TPA. Furthermore, our results are consistent with the view that GM-CSF or IL-3 receptor activation initiates the sequential activation of PKC and of the Na+/H+ antiporter, resulting in suppression of apoptosis in target cells.


De novo synthesis of NGF subunits in S-180 mouse sarcoma cell line.
It is an accepted hypothesis that the nerve growth factor protein (NGF) plays an important role in the development of vertebrate sympathetic and sensory ganglia and has effects on some central neurons. The best known NGF species is that isolated from mouse submaxillary gland, MSG-NGF. MSG-NGF can be isolated as a subunit containing protein, 7S-NGF, made up of three dissimilar subunits called alpha-, beta-, and gamma-NGF. Beta-NGF is the biologically active subunit and its synthesis in vivo and in vitro has been demonstrated. Less is known about the synthesis of the alpha- and gamma-NGF or the assembly of the subunits into the 7S complex. In order to develop a clonal model system for the study of NGF synthesis, processing and secretion, affinity chromatography techniques were applied to cell extracts of S180 mouse sarcoma, a cell line known to synthesize NGF. After incubating S180 cells in 35S-Methionine, cell extracts were exposed to antibody directed against alpha-NGF, gamma-NGF or beta-NGF covalently bound to Sepharose beads in order to elute and characterize the desired NGF subunits. Parallel experiments using immunoabsorbed [35S]Methionine-beta-NGF were carried out in the presence or absence of excess NGF, in order to demonstrate the specificity of this procedure. Affinity chromatography with a substrate analogue to arginine ester bound to Sepharose beads was also used to isolate de novo synthesized gamma-NGF.(ABSTRACT TRUNCATED AT 250 WORDS)


Good clinical practice research guidelines reviewed, emphasis given to responsibilities of investigators: second article in a series.
Investigators should be aware of the importance of Good Clinical Practice guideline compliance.


T-Cell Clustering in Neoplastic Follicles of Follicular Lymphoma.
The nonneoplastic microenvironment is abundant in follicular lymphoma. Its composition has been reported to be associated with the course of the disease. Lack of animal models hampers studies of interaction between lymphoma and bystander cells. We aimed to identify indicators of cellular interaction exemplified by nonrandom distribution of cell types within neoplastic follicles. Physiological germinal centers and follicles in follicular lymphoma were stained to identify macrophages, all T, follicular T-helper, dendritic and B cells. Density of cell types and cell distribution (spatial point pattern) were analyzed by digital image analysis. The density of all T, follicular T-helper and dendritic cells was higher in the dark zone than in the light zone of physiological germinal centers. Densities of cell types in follicular lymphoma were intermediate between the light and the dark zone. All cell types analyzed showed a completely random spatial distribution pattern within the dark and the light zone, respectively. In follicular lymphoma B cells and macrophages displayed complete spatial randomness. In contrast, all T cells, follicular T-helper cells and dendritic cells showed clustering of each individual cell type within a radius of 6-10 μm in the lymphoma. We conclude that the distribution of nonneoplastic cells within follicles of follicular lymphoma is not random. T cells and dendritic cells form clusters within the follicles, suggestive of sites of interaction between microenvironment and lymphoma cells. These clusters might help to understand the interaction of lymphoma cells with the microenvironment and might provide a structure for therapeutic intervention.


Spinal anaesthesia in obstetrics.
This article provides a comprehensive review of the technique, drugs of choice, and potential side effects and complications associated with the drugs used and the single-shot spinal anaesthesia (SSS) technique for caesarean delivery. Although neuraxial analgesia and anaesthesia are generally considered safe, all interventions come with potential adverse effects. As such, the practice of obstetric anaesthesia has evolved to minimize such risks. This review highlights the safety and efficacy of SSS for caesarean delivery while also discussing potential complications such as hypotension, postdural puncture headache, and nerve injury. In addition, drug selection and dosages are examined as well, emphasizing the importance of individualized treatment plans and close monitoring for optimal outcomes.


The IS10 transposase mRNA is destabilized during antisense RNA control.
RNA stability is an important component of gene expression, and antisense RNAs have been proposed to alter target RNA stability. We show here that the IS10 transposase mRNA, RNA-IN, is rendered unstable during control by the IS10 antisense RNA, RNA-OUT. Destabilization requires RNA-OUT/RNA-IN pairing and ribonuclease III cleavage. Independent of such cleavage, RNA-OUT is rendered unstable through disruption of its secondary structure. Pairing has no other obvious effects on RNA-IN transcription or stability. Nevertheless, RNA-IN destabilization is not required for antisense control in vivo. In the accompanying paper [Ma,C. and Simons, R.W. (1990) EMBO J., 9, 1267-1274 we show that pairing blocks ribosome binding to RNA-IN. Were it not for control at this level, destabilization would play a more prominent role.


Experimental field study of the relative costs and benefits to wild tamarins (Saguinus imperator and S. fuscicollis) of exploiting contestable food patches as single- and mixed-species troops.
Several species of tamarins form stable mixed-species troops in which groups of each species feed, forage, rest, and travel together during much of the year. Although the precise set of factors that facilitate this ecological relationship remains unclear, predator detection and foraging benefits are presumed to play a critical role in maintaining troop stability. In this work we present data from an experimental field study designed to examine how factors such as social dominance and within-patch foraging decisions affect the costs and benefits to tamarins of visiting feeding sites as single- and mixed-species troops. Our data indicate that when they exploited contestable food patches (sets of eight feeding platforms, two of which contained a 100-g banana), each tamarin species experienced foraging costs when they arrived as part of a mixed-species troop. These costs were found to be less severe for emperor tamarins because they were socially dominant to saddle-back tamarins and could displace them at feeding sites. We conclude that the foraging benefits to tamarins residing in mixed-species troops are asymmetrical, and that at feeding sites in which the amount of food in a patch is insufficient to satiate all troop members, even minor differences in the timing of return to food patches and changes in troop cohesion have a measurable effect on the costs and benefits to participating tamarin species.


Theory-Based Nursing Research: A Qualitative Evaluation of the Experiences of Nurse Educators.
Investigation of thoughts, experiences, and attitudes of nurse educators regarding theory-based research is important. Ultimately, nurse educators are the producers of nursing knowledge and providers of education. The aim of this study is to understand the experiences of nurse educators in selecting and using nursing theory to guide and inform the quality of their research. This study has a descriptive phenomenological design, and the sample was comprised of nine nurse educators who had experience with theory-based research. The data were collected via in-depth personal interviews using a semi-structured survey form. The data were analyzed with content analysis as described by Graneheim and Lundman. Four themes emerged from the results of the study: "awareness of theory," "meaning of theory-based research," "harmony with the theory," and "changing towards scholarship," with 10 subthemes. It was determined that theory-based research helps nurse educators to improve themselves in academic and personal terms. Although the process of translating theory into research presents several challenges, all participants expressed that theory-based research contributed to their "theory advancing nursing science."


Disseminated intravascular coagulation.
Etiology, pathogenesis, clinical features, laboratory findings, and therapy of disseminated intravascular coagulation (DIC) in the dog and the cat are reviewed.


Photocatalytic E→Z Contra-Thermodynamic Isomerization of Vinyl Silanes with Lewis Base.
Herein, we disclosed the contra-thermodynamic E→Z isomerization of alkenyl silanes, according to the in situ formation of a chromophoric species, in the presence of rac-BINAP as the catalyst. The reaction carried out in DMSO or CH3 CN under irradiation at 405 nm allowed the interconversion of the E-isomers into the Z-congeners in good to excellent yields and outstanding Z/E selectivities, on 18 examples. Finally, the mechanism of this E→Z isomerization was studied to get insight into the reaction mechanism.


NRF2 inhibition represses ErbB2 signaling in ovarian carcinoma cells: implications for tumor growth retardation and docetaxel sensitivity.
NF-E2-related factor 2 (NRF2) is a transcription factor that regulates the expression of various antioxidant and detoxifying enzymes. Although the benefit of NRF2 in cancer prevention is well established, its role in cancer pathobiology was recently discovered. In this study, the role of NRF2 in tumor growth and docetaxel sensitivity was investigated in ErbB2-overexpressing ovarian carcinoma SKOV3 cells. Interfering RNA-mediated stable inhibition of NRF2 in SKOV3 cells repressed NRF2 signaling, resulting in cell growth arrest at G(0)/G(1) phase and tumor growth retardation in mouse xenografts. Microarray analysis revealed that ErbB2 expression is substantially reduced in NRF2-inhibited SKOV3 and this was further confirmed by RT-PCR and immunoblot analysis. Repression of ErbB2 led to a decrease in phospho-AKT and enhanced p27 protein, reinforcing the effect of NRF2 knockdown on SKOV3 growth. Furthermore, NRF2 inhibition-mediated ErbB2 repression increases the sensitivity of these cells to docetaxel cytotoxicity and apoptosis. The linkage between NRF2 and ErbB2 was confirmed in the ErbB2-positive breast cancer cell line BT-474: NRF2 knockdown suppressed ErbB2 expression and enhanced docetaxel sensitivity. Our results provide insight into the coordinated regulation of signaling molecules responding to environmental stress and suggest that NRF2 modulation might be a therapeutic strategy to limit tumor growth and enhance sensitivity to taxane-based chemotherapy.


Monitoring of spasticity and functional ability in individuals with incomplete spinal cord injury with a functional electrical stimulation cycling system.
The aim of this study was to investigate the integration of motor function and spasticity assessment of individuals with spinal cord injury into cycling therapy. Twenty-three participants with incomplete spinal cord injury performed 18 training sessions (standard deviation (SD) 14) on an instrumented tricycle combined with functional electrical stimulation. Each therapy session included a power output test to assess the participants' ability to pedal actively and a spasticity test routine that measures the legs' resistance to the pedalling motion. In addition, the required time for the therapy phases was monitored. The results of the power output test showed a monthly increase in power output of 4.4 W (SD 13.7) at 30 rpm and 18.2 W (SD 23.9) at 60 rpm. The results of the spasticity assessment indicate a 12.2 W (SD 9.7) reduction in resistance at 60 rpm after the FES training for the subject group with spasticity. In clinical use over a time-period of 2 years this combined form of therapy and motor function assessment was well accepted by participants. The active power output test and the spasticity test routine offered a proper tool to monitor participants' progress in functional rehabilitation and changes in spasticity.


Influence of pH, layer charge location and crystal thickness distribution on U(VI) sorption onto heterogeneous dioctahedral smectite.
The UO2(2+) adsorption on smectite (samples BA1, PS2 and PS3) with a heterogeneous structure was investigated at pH 4 (I=0.02M) and pH 6 (I=0.2M) in batch experiments, with the aim to evaluate the influence of pH, layer charge location and crystal thickness distribution. Mean crystal thickness distribution of smectite crystallite used in sorption experiments range from 4.8nm (sample PS2), to 5.1nm (sample PS3) and, to 7.4nm (sample BA1). Smaller crystallites have higher total surface area and sorption capacity. Octahedral charge location favor higher sorption capacity. The sorption isotherms of Freundlich, Langmuir and SIPS were used to model the sorption experiments. The surface complexation and cation exchange reactions were modeled using PHREEQC-code to describe the UO2(2+) sorption on smectite. The amount of UO2(2+) adsorbed on smectite samples decreased significantly at pH 6 and higher ionic strength, where the sorption mechanism was restricted to the edge sites of smectite. Two binding energy components at 380.8±0.3 and 382.2±0.3eV, assigned to hydrated UO2(2+) adsorbed by cation exchange and by inner-sphere complexation on the external sites at pH 4, were identified after the U4f7/2 peak deconvolution by X-photoelectron spectroscopy. Also, two new binding energy components at 380.3±0.3 and 381.8±0.3eV assigned to AlOUO2(+) and SiOUO2(+) surface species were observed at pH 6.


Hypertension Control Rate Should be Defined Consistently and Used to Motivate Action to Improve.
Hypertension has been poorly controlled with the old target of less than 140/90 (mmHg). Currently, the average control rate in the United States is about 50% with the old goal of 140/90. If the new goal of 130/80 is used, the control rate would dramatically decrease. For hypertension management, the traditional stepped-care method needs to be replaced with new approaches using single-pill combination pharmacotherapy (polypill) or using hemodynamic data for drug selection and titration to target underlying cardiovascular abnormalities when cardiovascular disease is present. With the old goal of 140/90, these new approaches have achieved a control rate of 90%. The evidence indicates that new models of therapy and patient support can dramatically improve control rate. However, a key requirement is the will to act. Standardizing and publishing the control rate per medical group could motivate clinicians to implement best practices and expedite a rapid shift to better hypertension management.


A method for bevelling of microelectrodes by means of vibration.
A technique for the rapid bevelling of glass and metallic microelectrodes is described. The method utilizes end friction of the electrode tips on the fine-grained surface of a quartz plate vibrating at the mechanical resonance frequency of the system. A electromagnetic vibrator is supplied with alternating current at a frequency equal to the mechanical resonance frequency of the system (200-300 s-1).


Inverse Resolution Limit of Partition Density and Detecting Overlapping Communities by Link-Surprise.
Finding overlapping communities of complex networks remains a challenge in network science. To address this challenge, one of the widely used approaches is finding the communities of links by optimizing the objective function, partition density. In this study, we show that partition density suffers from inverse resolution limit; it has a strong preference to triangles. This resolution limit makes partition density an improper objective function for global optimization. The conditions where partition density prefers triangles to larger link community structures are analytically derived and confirmed with global optimization calculations using synthetic and real-world networks. To overcome this limitation of partition density, we suggest an alternative measure, Link Surprise, to find link communities, which is suitable for global optimization. Benchmark studies demonstrate that global optimization of Link Surprise yields meaningful and more accurate link community structures than partition density optimization.


Disengagement of motor cortex from movement control during long-term learning.
Motor learning involves reorganization of the primary motor cortex (M1). However, it remains unclear how the involvement of M1 in movement control changes during long-term learning. To address this, we trained mice in a forelimb-based motor task over months and performed optogenetic inactivation and two-photon calcium imaging in M1 during the long-term training. We found that M1 inactivation impaired the forelimb movements in the early and middle stages, but not in the late stage, indicating that the movements that initially required M1 became independent of M1. As previously shown, M1 population activity became more consistent across trials from the early to middle stage while task performance rapidly improved. However, from the middle to late stage, M1 population activity became again variable despite consistent expert behaviors. This later decline in activity consistency suggests dissociation between M1 and movements. These findings suggest that long-term motor learning can disengage M1 from movement control.


Highly selective separation of eucalyptus hemicellulose by salicylic acid treatment with both aromatic and hydroxy acids.
Aromatic and hydroxyl acid treatments demonstrate their respective characteristics for the separation of lignocellulosic biomass. In this study, the effect of salicylic acid (SA-A) treatment on the separation of eucalyptus components with both aromatic and hydroxyl acid properties was analyzed. The optimal conditions were SA-A concentration 9.0%, reaction temperature 140 °C and time 75 min. The separation yield of xylose was 85.93%. The separation of cellulose and lignin was inhibited by SA-A treatment in contrast to the separation by glycolic acid and p-toluenesulfonic acid treatment. Moreover, SA-A treatment resulted in a larger fiber crystallinity index and higher thermal stability. The SA-A-treated samples contained lignin that was rich in β-O-4 and hydroxyl groups. The degradation and condensation of lignin was inhibited. The selectivity of aromatic acids for separating hemicellulose and protecting the lignin structure using hydroxy acids was demonstrated. Thus, new and efficient organic acid treatments can be developed.


HPV antibody levels and clinical efficacy following administration of a prophylactic quadrivalent HPV vaccine.
The efficacy of the quadrivalent Human Papillomavirus (HPV) vaccine is thought to be mediated by humoral immunity. We evaluated the correlation between quadrivalent HPV vaccine-induced serum anti-HPV responses and efficacy. 17,622 women were vaccinated at day 1, and months 2 and 6. At day 1 and at 6-12 months intervals for up to 48 months, subjects underwent Papanicolaou and genital HPV testing. No immune correlate of protection could be found due to low number of cases. Although 40% of vaccine subjects were anti-HPV 18 seronegative at end-of-study, efficacy against HPV 18-related disease remained high (98.4%; 95% CI: 90.5-100.0) despite high attack rates in the placebo group. These results suggest vaccine-induced protection via immune memory, or lower than detectable HPV 18 antibody titers.


Contributions of infertility treatment to very-low-birth-weight multiple birth infants receiving neonatal intensive care.
This study was undertaken to determine proportions of very-low-birth-weight (VLBW) multiple birth infants receiving neonatal intensive care whose mothers received various types of infertility treatment and to evaluate infertility treatment-associated morbidity and mortality. Study infants were multiples with birth weight 401 to 1500 g cared for in Cincinnati neonatal intensive care units from January 1996 to December 2000. Data were obtained retrospectively from the National Institute for Child Health and Human Development Neonatal Research Network registry. Use of infertility treatment (in vitro fertilization, injection or oral ovulation, and intrauterine insemination) was determined by maternal interview or chart review. The generalized estimating equation approach to logistic regression was used. The study included 382 infants of 212 mothers: 201=spontaneous conception (53%), 93=in vitro fertilization (24%), 55=injection (14%), 15=oral (4%), and 18=intrauterine insemination (5%). Neither gestational age nor birth weight differed between groups. More female (58%, P=.003) and white infants (95%, P<.001) resulted from infertility treatment-induced pregnancies than from spontaneous pregnancies. Advancing gestational age significantly decreased odds for all outcomes. Of VLBW multiples receiving neonatal intensive care, 47% are associated with infertility treatment. Infertility treatment does not influence outcomes in VLBW multiples.


Efficacy of herbal anti-microbial soap in Tinea corporis: A randomized controlled study.
Curcuma longa L., Azadirachta indica A Juss. Cassia tora L. has been used in Unani medicine for various skin ailments. Several researches have been conducted on these plants which have shown anti-microbial, anti-bacterial, anti-fungal, antiviral, anti-oxidant, wound healing, anti-inflammatory, and immune modulation activities. Skin diseases and the use of these drugs are mentioned in classical Unani literature like The Canon of medicine, Continens Liber, Hippocratic treatments, The Complete Book of the Medical Art etc. AIM: The aim of the study was to formulate anti-microbial soap and to evaluate its clinical efficacy of in the management of Tinea corporis. The anti-microbial soap was prepared by hydroalcholic extracts of Curcuma longa L., Azadirachta indica A Juss. and Cassia tora L. The prepared soap was evaluated for various physicochemical parameters, microbiological evaluation, stability study, skin irritation, In-vitro anti-microbial activity, GCMS analysis, and a clinical trial was carried out to evaluate its efficacy. A Single Blind Randomized Placebo Controlled trail on 30 patients aged between 18 and 60 years of either gender was carried out. The participants were randomly allocated to receive either anti-microbial soap or Placebo soap for 4 weeks. Subjective parameters including erythema, pruritis and desquamation were assessed weekly while as objective parameter including Photograph of lesion, Total Symptom Score (TSS) and KOH mount was assessed at baseline and at the end of the trial. The improvement in subjective parameters was found significant in test group. Erythema, scaling, and desquamation was completely relieved by 70%, 80% and 25% patients respectively in test group while as none of the patients got complete relief in control group. There was statistically significant reduction in average TSS 8.65 ± 0.6708 to 3.05 ± 1.35 p < 0.001. KOH mount turned negative in 80% patients in test group while as only 20% turned negative in control group. It is concluded that Unani drugs can be utilized in better way by modifying into a convenient dosage form. Anti-microbial soap was formulated by adding minimal additives to achieve effectiveness, with cost effective benefits and less or no side effects. Anti-microbial soap was effective in management of management of Tinea corporis. Moreover further studies on large sample size are required to fine-tune these observations.


Child passenger restraint use and emergency department--reported injuries: a special study using the National Electronic Injury Surveillance System-All Injury Program, 2004.
In 2004, more than 180,000 child passengers aged <or=12 years sought care in U.S. hospital emergency departments (EDs) for injuries sustained in motor-vehicle crashes (MVCs). We expanded the National Electronic Injury Surveillance System-All Injury Program for 635 injured children aged <or=12 years treated at 15 hospital EDs in 2004 by collecting multiple injury diagnoses and interviewing parents about MVC circumstances. Nine percent of the children were unrestrained and 36% were inappropriately restrained. Blacks and Hispanics were about six times more likely to be unrestrained than Non-Hispanic Whites (12% and 14%, respectively, vs. 2%). Seventy-seven percent of inappropriate restraint use occurred among children aged 4-8 years, who were prematurely placed in seatbelts. Eight percent of children required hospitalization; unrestrained children were three times more likely to be hospitalized than restrained children (21% vs. 7%). Age-appropriate restraint use should be promoted for child passengers, particularly among Blacks, Hispanics, and children riding in trucks.


Impact of cardiovascular risk factors on chronic abdominal pain after laparoscopic gastric bypass.
Patients with chronic pain after laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery frequently report intense postprandial abdominal pain. Reduced blood supply due to atherosclerosis was hypothesised to be a contributing cause. This was a retrospective, single-centre cohort study including all patients with LRYGB surgery from 2010 through 2015. Data from multiple registries, medical records and a questionnaire were used. The risk of chronic abdominal pain was analysed using multivariate logistic regression. We included 787 patients. Among these, 177 (23%) patients were defined as having chronic abdominal pain. The median follow-up was 63 months. When investigating the impact of risk factors for atherosclerosis including dyslipidaemia, Type 2 diabetes, hypertension, smoking and cardiovascular co-morbidities, the "atherosclerosis composite score" was a significant risk factor (odds ratio = 1.22, 95% confidence interval: 1.02-1.45). In a multivariate model specifically investigating dyslipidaemia, the association with chronic abdominal pain was non-significant. In this exploratory study, development of chronic abdominal pain was significantly associated with risk factors for atherosclerosis, but the specific association with dyslipidaemia was non-significant. The study was supported by the Danish Medical Association's Research Foundation and the Edgar Schnohr Foundation. The study was approved by the Danish Data Protection Agency (No. REG-063-2017).


Protein arginine methylation regulates insulin signaling in L6 skeletal muscle cells.
Protein N-arginine methyltransferase (PRMT)1 catalyzes arginine methylation in a variety of substrates, although the potential role of PRMT1 in insulin action has not been defined. We therefore investigated the effect of PRMT1-mediated methylation on insulin signaling and glucose uptake in skeletal L6 myotubes. Exposure of L6 myotubes to insulin rapidly induced translocation of PRMT1 and increased its catalytic activity in membrane fraction. Several proteins in the membrane fraction were arginine-methylated after insulin treatment, which were inhibited by pretreatment with an inhibitor of methyltransferase, 5'-deoxy-5'-(methylthio)adenosine (MTA), or a small interfering RNA against PRMT1 (PRMT1-siRNA). Inhibition of arginine methylation with MTA or PRMT1-siRNA diminished later phase of insulin-stimulated tyrosine phosphorylation of insulin receptor (IR) beta and IRS-1, association of IRS-1 with p85alpha subunit of PI3-K, and glucose uptake. Our results suggest that PRMT1-mediated methylation serves as a positive modulator of IR/IRS-1/PI3-K pathway and subsequent glucose uptake in skeletal muscle cells.


An Integrated Computer-Aided Design and Manufacturing Workflow for Synthetic Biology.
Biological computer-aided design and manufacturing (bioCAD/CAM) tools facilitate the design and build processes of engineering biological systems using iterative design-build-test-learn (DBTL) cycles. In this book chapter, we highlight some of the bioCAD/CAM tools developed and used at the US Department of Energy (DOE) Joint Genome Institute (JGI), Joint BioEnergy Institute (JBEI), and Agile BioFoundry (ABF). We demonstrate the use of these bioCAD/CAM tools on a common workflow for designing and building a multigene pathway in a hierarchical fashion. Each tool presented in this book chapter is specifically tailored to support one or more specific steps in a workflow, can be integrated with the others into design and build workflows, and can be deployed at academic, government, or commercial entities.


Graphene oxide nanosheets versus carbon nanofibers: Enhancement of physical and biological properties of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) films for biomedical applications.
Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a microbial biodegradable polymer with a wide range of potential industrial applications. However, its biomedical uses could increase exponentially if certain physical and biological properties were enhanced without compromising on the non-cytotoxic property of this biocompatible polymer. Graphene oxide (GO) nanosheets and carbon nanofibers (CNFs) have proven to be very promising reinforcing agents for the development of new composite materials. Therefore, PHBV films were prepared with 1% w/w of GO nanosheets or CNFs with the aim of enhancing their compression performance, thermal behaviour, wettability and cell adhesion using canine adipose-derived mesenchymal stem cells, and antibacterial activity against the model bacterium Staphylococcus aureus. The results of this study showed that both nanomaterials produced similar enhancements of the physical properties. However, PHBV/GO exhibited higher proliferative activity against time, cell adhesion and antibacterial activity than that of PHBV/CNFs. Nonetheless, both PHBV/GO and PHBV/CNFs composite films have shown considerable promise for biomedical applications.


Articulatin B chain induced dendritic cells maturation and driven type I T helper cells and cytotoxic T cells activation.
Articulatin (AT), purified from the Chinese mistletoe (Viscum articulatum), belongs to the family of type II ribosome-inactivating proteins (RIPs) that contain two subunits, the A and B chains. The B chain of AT is believed to function by means of interacting with the galactose moiety of glycoproteins or glycolipids on the cell membrane and is internalized into cells through endocytosis. In the study, we aim to investigate the immunomodulatory effects of recombinant articulatin B chain (rATB) on mouse bone marrow-derived dendritic cells (BM-DCs). Detection of surface markers expression on BM-DCs by flow cytometry. Analysis of RNA and protein expression by RNAseq and Western blotting assays. Assessment of the adaptive immune responses using an in vivo mouse model. Our study presents novel results showing the activation of mouse BM-DCs by rATB, which leads to the induction of CD80, CD86, and MHC II expression as well as primed type I CD4+ T cell differentiation and CD8+ T cell activation. RNAseq and Western blotting assays revealed rATB-induced BM-DC activation to be dependent on the MAPK and NF-κB signaling pathways. In a mouse model, rATB was observed to have adjuvant effects that induced an antigen-specific Th1 immune response. Based on in vitro and in vivo assays, this study shows rATB acting as a potential adjuvant that induces BM-DC activation and antigen-specific Th1 related immune response. rATB might have potential applicability in the development of vaccines against pathogens and tumors.