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The human immunodeficiency virus epidemic continues in sub-Saharan Africa, and particularly affects adolescent girls and women who have limited access to antiretroviral therapy. Here we report that the risk of vaginal simian immunodeficiency virus (SIV)mac251 acquisition is reduced by more than 90% using a combination of a vaccine comprising V1-deleted (V2 enhanced) SIV envelope immunogens with topical treatment of the zinc-finger inhibitor SAMT-247. Following 14 weekly intravaginal exposures to the highly pathogenic SIVmac251, 80% of a cohort of 20 macaques vaccinated and treated with SAMT-247 remained uninfected. In an arm of 18 vaccinated-only animals without microbicide, 40% of macaques remained uninfected. The combined SAMT-247/vaccine regimen was significantly more effective than vaccination alone. By analysing immune correlates of protection, we show that, by increasing zinc availability, SAMT-247 increases natural killer cytotoxicity and monocyte efferocytosis, and decreases T-cell activation to augment vaccine-induced protection.

The growing presence of Unmanned Aerial Vehicles (UAVs) in all sectors of society poses new security threats to civilian and military sectors. In response, new UAV detection systems have and are being developed. Current systems use techniques such as Radio Detection And Ranging (RADAR), visual recognition, and Radio Frequency (RF). Another promising solution for UAV detection uses acoustic emissions. Past researchers demonstrated the ability to use UAV acoustic signatures to determine whether a UAV carries a payload and the weight of that payload at close range with high-quality microphones. This research expands the field of study by performing acoustic payload detection using cell phones and at farther range by developing the system called HurtzHunter. The system collects audio data and extracts Mel-Frequency Cepstrum Coefficients (MFCCs) to train Support Vector Machines (SVMs). The HurtzHunter system tests acoustic payload detection with one high-quality microphone and six different cell phones at 7 m - 100 m ground distance from the UAV. At each distance, the experiment runs 6 flights each with a unique payload attached to the UAV. The HurtzHunter design achieves an 88.26% - 99.93% payload prediction accuracy depending on the configuration.

Intraoperative teaching is a critical component of surgery residents' education. Although prior studies have investigated best practices from the viewpoint of the expert educator, the perspective of the learner has been less explored. This study examined the ideal faculty teaching behaviors that optimize intraoperative teaching from the surgical residents' perspective.Using a grounded theory method, this study explored perspectives on intraoperative faculty teaching qualities of 5 focus groups of categorical clinical general surgical residents of the same postgraduate year from June to August 2021. Focus group discussions were recorded, transcribed, and coded. Emerging themes were identified, along with their corresponding subthemes.Thirty-nine general surgery residents participated in the focus groups. Overall, 6 themes emerged regarding resident priorities of intraoperative teaching, with 10 subthemes. Themes included the following: (1) character, with subthemes of caring, respect for resident, and self-control; (2) intraoperative skill, with subthemes of clinical and operative skill and modeling leadership in the operating room; (3) instructional approach; (4) feedback, with subthemes of content of feedback and debriefing; (5) discernment of resident needs, with subthemes of managing expectations, individualizing instruction, and autonomy; and (6) variety of teachers.Certain tangible strategies, such as demonstrating genuine care for the learner, using clear directional words, and giving actionable feedback, were considered vital by residents. In the development of great surgical educators, the emphasis should not be on conformity to a single idealized teaching style but should celebrate and encourage diversity of personas and teaching styles within a department or program.

Accounting for poro-mechanical effects in full-field reservoir simulation studies and uncertainty quantification workflows using complex reservoir models is challenging, mainly because of the high computational cost. We hence introduce an alternative approach that couples hydrodynamics through existing flow diagnostics simulations with poro-mechanics to screen the impact of coupled poro-mechanical processes on reservoir performance without significantly increasing computational overheads. In flow diagnostics, time-of-flight distributions and influence regions can be used to characterise the flow field in the reservoir, which depends on the distribution of petrophysical properties that are altered due to production-induced changes in pore pressure and effective stress. These extended flow diagnostics calculations hence enable us to quickly screen how the dynamics in the reservoirs (e.g. reservoir connectivity, displacement efficiency, and well allocation factors) are affected by the complex interactions between poro-mechanics and hydrodynamics. Our poro-mechanically informed flow diagnostics account for steady-state and single-phase flow conditions based on the poro-elastic theory and assume that the reservoir does not contain fractures. Fluid flow and rock deformation calculations are coupled sequentially. The equations are discretised using a finite-volume method with two-point flux-approximation and the virtual element method, respectively. The solution of the coupled system considers stress-dependent permeabilities. Due to the steady-state nature of the calculations and the effective proposed coupling strategy, these calculations remain computationally efficient while providing first-order approximations of the interplay between poro-mechanics and hydrodynamics, as we demonstrate through a series of case studies. The extended flow diagnostic approach hence provides an efficient complement to traditional reservoir simulation and uncertainty quantification workflows and enable us to assess a broader range of reservoir uncertainties.

Pelvic organ prolapse (POP) is a gynecological problem that can worsen the psychosocial, economic, and sexual function of women and often relapses after surgery. POP is associated with weakness of the pelvic floor supporting structures. Pelvic organ prolapse is associated with a reduced quality of life for millions of women worldwide. The purpose of this study was to determine the role of the MMP-1 rs 1799750 gene polymorphisms as a risk factor for pelvic organ prolapse in Balinese women. This observational case-control study involves 30 patients with pelvic organ prolapse as the case group and 30 patients without pelvic organ prolapse as the control group. The study was conducted at the Integrated Biomedical Laboratory, Faculty of Medicine, Udayana University. Three milliliters of venous blood samples were taken from each patient and DNA examination was performed to determine MMP-1 gene polymorphisms. Risk assessment of the MMP-1 gene polymorphism for pelvic organ prolapse was done by controlling for confounding variables, including age, parity, heavy work, body mass index, menopausal status, and history of hysterectomy, through multivariate logistic regression conditional test. Result from this study is the MMP-1 gene polymorphism increased the risk of pelvic organ prolapse 4.33 times compared to non-prolapsed in Balinese women (OR 4.33, 95%CI 1.20 -15.61, p = 0.020). After controlling for various confounding variables, MMP-1 gene polymorphism still increased the risk of pelvic organ prolapse up to 5.52 times (AOR 5.52, 95%CI 1.352-22.50, p = 0.02). Conclusion from this study is MMP-1 gene polymorphism significantly increases the risk of pelvic organ prolapse in Balinese women.

This study aims to determine the role of type B progesterone receptor gene polymorphisms as a risk factor for pelvic organ prolapse in Balinese women. This paired case-control study involves 29 patients with pelvic organ prolapse as the case group and 29 patients without pelvic organ prolapse as the control group. The study was conducted at Sanglah Hospital, Denpasar and the Integrated Biomedical Laboratory, Faculty of Medicine, Udayana University. Three milliliters of venous blood samples were taken from each patient and PCR examination was performed to determine the type b progesterone receptor gene polymorphisms. Risk assessment of the type b progesterone receptor gene polymorphism for pelvic organ prolapse was done by controlling for confounding variables, including age, parity, body mass index, occupation, menopausal status, and history of hysterectomy, through multiple logistic regression tests. The type b progesterone receptor gene polymorphism increased the risk of pelvic organ prolapse three times compared to non-prolapsed in Balinese women (OR 3.90, 95%CI 1.16-13.07, p = 0.023). After controlling for various confounding variables, type b progesterone receptor gene polymorphism still increased the risk of pelvic organ prolapse up to four times (AOR 4.54, 95%CI 1.16-17.68, p = 0.029). The type b progesterone receptor gene polymorphism significantly increases the risk of pelvic organ prolapse in Balinese women.

Introduction We assessed students' perception of the impact of the pandemic on their well-being, education, academic achievement, and whether grit and resilience alter students’ ability to mitigate the stress associated with disruptions in education. We hypothesized that students would report a negative impact, and those with higher grit and resilience scores would be less impacted. Methods A multidisciplinary team of educators created and distributed a survey to medical students. Survey results were analyzed using descriptive statistics, ANOVA, and multivariate linear regressions. A p-value

Aflatoxins are carcinogens mainly produced by Aspergillus flavus and A. parasiticus in susceptible crops, including pistachio. The primary inoculum sources of these pathogens are plant debris in the orchard soils. In Californian fields, one approach to controlling aflatoxin contamination is based on releasing the atoxigenic strain of A. flavus AF36 in inoculated (coated) sorghum grains (AF36 Prevail). However, this control method can fail due to poor sporulation of the AF36 strain or sorghum grain losses due to predation. In 2008 and 2018, we showed that toxigenic and atoxigenic isolates of Aspergillus spp. frequently colonized fallen inflorescences of male pistachio trees. Under controlled conditions, strain AF36 profusely colonized pistachio male inflorescences when humidity was higher than 90%. However, there were significant differences between types of inflorescence (aerial > fallen). In 2016, we considerably (P = 0.015) increased the population of AF36 on the canopies of trees when fallen inflorescences were inoculated with AF36, compared with untreated trees. In 2017 and 2018, these differences were not detected (P > 0.05) due to cross-contamination of strain AF36 between seasons and neighboring plots. In any case, the density of AF36 spores on the canopy of the inflorescence-treated trees was similar (P > 0.05) to that on trees treated with the commercial product. Here, we present a new method for applying strain AF36 based on using a natural, abundant, and uniformly distributed substrate in pistachio fields, and we discuss how it can be improved. Furthermore, our results indicate that, in pistachio orchards where biocontrol practices are not conducted, eliminating this important source of toxigenic Aspergillus inoculum is recommended.

Background: Psychosocial stress, particularly chronic unpredictable stress (CUS) has been identified as a risk factor for cardiovascular disease, but the effects of CUS on left ventricle (LV) function, geometry and systemic hemodynamics remains unclear. Moreover, whether and to what degree CUS activates intracellular formation of the inflammasome, including the NOD-LRR pyrin containing protein 3 (NLRP3) remains unknown. Accordingly, the central hypothesis of this project was that in a murine model of CUS, shifts in LV geometry and systemic hemodynamics would occur and be associated with the induction of NLRP3. Methods and Results: Mice (C57BL/6, 10wks of age, equal sex, n=16) were subjected to CUS for 4 weeks which entailed daily random stressors including tilted cage, wet bedding, and overnight light. Referent age and sex matched non CUS mice served as controls (n=16). LV function was assessed by high fidelity ultrasound and blood pressure measurements by tail cuff for both referent control and CUS mice. The changes in ambient heart rate (HR), LV end-systolic volume (LVEDV), and systolic blood pressure (SBP) were expressed as a function of referent control. All results are reported as mean ± SEM. While LV ejection fraction was equivalent between CUS and control groups (70 ± 3 vs. 67 ± 3%, respectively, p=0.48), HR trended higher (4.5 ± 3.1%, p=0.08), LVEDV was lower (-11 ± 5%, p=0.03) and SBP was elevated (12.1 ± 4.9%, p=0.04) - all indicative of heightened sympathetic tone. LV myocardial NLRP3 (rtPCR) was increased (1.47 ± 0.22 fold change, p=0.04) with CUS as was IL-1β (1.43 ± 0.20 fold change, p=0.05), a downstream cytokine activated by NLRP3. Conclusion: CUS, in and of itself, shifts LV geometry, causes mild hypertension and induction of the myocardial inflammasome- all of which would exacerbate/contribute to cardiovascular disease. This work was supported in part by National Institutes of Health grant R01HL130972-01A1 (F.G.S.), R01HL5949 (F.G.S.), RO1DK132948 (C.W. & F.P.), R01 MH129798 (SKW) and P20GM109091 (F.H.) as well as a Merit Award from the Veterans Health Administration, BX000168-10A1 (F.G.S.), BX005320 (F.G.S.), BX002604 (M.J.R.), and VISN7 RDA (F.H.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Observational studies have reported an inverse association between vitamin D intake and breast cancer risk. We examined whether vitamin D supplementation in high-risk premenopausal women reduces mammographic density (MD), an established breast cancer risk factor. We conducted a multicenter randomized double-blind placebo-controlled trial in premenopausal women at high risk for breast cancer [5-year risk ≥ 1.67%, lifetime risk ≥ 20%, lobular carcinoma in situ, prior stage 0–II breast cancer, hereditary breast cancer syndrome, or high MD (heterogeneously/extremely dense)], with a baseline serum 25-hydroxyvitamin D [25(OH)D] ≤ 32 ng/mL. Participants were randomized to 12 months of vitamin D3 20,000 IU/week or matching placebo. The primary endpoint was change in MD from baseline to 12 months using the Cumulus technique. Secondary endpoints included serial blood biomarkers [25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)D), insulin-like growth factor (IGF)-1, IGF-binding protein-3] and MD change at 24 months. Among 208 women randomized, median age was 44.6 years, 84% were white, 33% had baseline 25(OH)D < 20 ng/mL, and 78% had high baseline MD. Comparing the active and placebo groups at 12 months, MD changes were small and did not significantly differ. Mean MD changes at 12 and 24 months were −0.3% and −1.2%, respectively, in the active arm and +1.5% and +1.6% with placebo (P > 0.05). We observed a mean change in serum 25(OH)D of +18.9 versus +2.8 ng/mL (P < 0.01) and IGF-1 of −9.8 versus −1.8 ng/mL (P = 0.28), respectively. At 12 months, MD was positively correlated with serum IGF-1 and IGF-1/IGFBP-3 (P < 0.01). This trial does not support the use of vitamin D supplementation for breast cancer risk reduction.

Table of baseline characteristics of participants evaluable for the primary endpoint

Aim: To determine whether term pregnant women with human immunodeficiency virus infection who received antiretroviral therapy had high apoptosis inducing factor expression in the placenta. Methods: This cross-sectional analytical study was conducted at Sanglah General Hospital, Denpasar, and educational network hospitals. Subjects collected were termed pregnant women with HIV (+) who received antiretroviral therapy (ART) 6 months as a risk group and pregnant women with HIV (-) as a non-risk group. AIF expression was assessed by immunohistochemical examination of placental tissue. The AIF expression cut-off value was determined by constructing a receiver operating characteristics (ROC) curve. The chi-square test assessed the difference in proportion by displaying the prevalence ratio (RP) results. The significance of this study was p

Introduction: Bacteriuria in pregnancy is quite common, with the prevalence of asymptomatic bacteriuria occurring in about 2-5% of pregnancies, acute cystitis occurring in 1.3% of pregnancies and acute pyelonephritis occurring in about 3%. If not treated properly, asymptomatic bacteriuria can increase the risk of pyelonephritis and the incidence of low birth weight (LBW). This study aims to describe the characteristics of patients with bacteriuria in pregnant women at Sanglah Hospital. Acknowledging the characteristics of patients with bacteriuria may help the screening process establish an early diagnosis and management. Methods: This study is a retrospective descriptive study carried out at Sanglah Hospital Denpasar from January 2018 to January 2020. Pregnant women diagnosed with bacteriuria in pregnancy from January 2018 to January 2020 at Sanglah Hospital Denpasar who had met the inclusion criteria and did not meet the exclusion criteria were included in the study. Data regarding the patient’s age, gestational age when bacteriuria was diagnosed, UTI complaints, bacterial urine levels, and culture results were collected for each subject. Results: Based on the results of this study, it was found that the prevalence of positive bacteriuria from January 2018 to 2020 was 0.89%. Most of the pregnant women diagnosed with bacteriuria were aged 20-35 years (77.1%), had gestational age of 0 - 28 weeks (64.9%), were multigravida (52.7%), and had high school education level (50.8%). The majority of pregnant women who experience bacteriuria were included in the group of asymptomatic bacteriuria (64.9%). The urinalysis results on pregnant women with bacteriuria showed that most of the pregnant women (45.6%) had +1 bacteria levels, followed by +2 and +3 bacteria levels, namely 28% and 26.4%, respectively. Conclusion: Bacteriuria in pregnancy is still a problem that is often encountered in daily practice

Summary Accounting for poro-mechanical effects in full-field reservoir simulation studies and uncertainty quantification workflows is still limited, mainly because of their high computational cost. We introduce a new approach that couples hydrodynamics and poro-mechanics with dual-porosity flow diagnostics to analyze how poro-mechanics could affect reservoir dynamics in naturally fractured reservoirs without significantly increasing computational overhead. Our new poro-mechanically informed dual-porosity flow diagnostics account for steady-state and single-phase flow conditions in the fractured medium while the fracture-matrix fluid exchange is approximated using a physics-based transfer rate coefficient, which models two-phase flow using an analytical solution for spontaneous imbibition or gravity drainage. The deformation of the system is described by the dual-porosity poro-elastic theory, which is based on mixture theory and micromechanics to compute the effective stresses and strains of the rock matrix and fractures. The solutions to the fluid flow and rock deformation equations are coupled sequentially. The governing equations for fluid flow are discretized using a finite-volume method with two-point flux-approximation while the governing equations for poro-mechanics are discretized using the virtual element method. The solution of the coupled system considers stress-dependent permeabilities for fractures and matrix. Our framework is implemented in the open-source MATLAB Reservoir Simulation Toolbox (MRST). We present a case study using a fractured carbonate reservoir analog to illustrate the integration of poro-mechanics within the dual-porosity flow diagnostics framework. The extended flow diagnostics calculations enable us to quickly screen how the dynamics in fractured reservoirs (e.g., reservoir connectivity, sweep efficiency, and fracture-matrix transfer rates) are affected by the complex interactions between poro-mechanics and fluid flow where changes in pore pressure and effective stress modify petrophysical properties and hence affect reservoir dynamics. Because of the steady-state nature of the calculations and the effective coupling strategy, these calculations do not incur significant computational overheads. They provide an efficient complement to traditional reservoir simulation and uncertainty quantification workflows because they enable us to assess a broader range of reservoir uncertainties (e.g., geological, petrophysical, and hydromechanical uncertainties). The capability of studying a much broader range of uncertainties allows the comparison and ranking from a large ensemble of reservoir models and select individual candidates for more detailed full-physics reservoir simulation studies without compromising on assessing the range of uncertainties inherent to fractured reservoirs.

Flow in fractures is sensitive to their geometrical surface characteristics. The surface can undergo deformation if there is a change in stress. Natural fractures have complex geometries and rough surfaces which complicates the modelling of deformation and fluid flow. In this paper, we present a computational model that takes a digital image of a rough fracture surface and provides a stress–permeability relationship. The model is based on a first-principle contact mechanics approach at the continuum scale. Using this first principle approach, we investigate numerically the effect of fracture surface roughness and shifting of surfaces on the permeability evolution under applied stress and compare the results with laboratory experiments. A mudrock core fracture surface was digitalized using an optical microscope, and 2D cross sections through fracture surface profiles were taken for the modelling. Mechanical deformation is simulated with the contact mechanics based Virtual Element Method solver that we developed within the MATLAB Reservoir Simulation Toolbox platform. The permeability perpendicular to the fracture cross section is determined by solving the Stokes equation using the Finite Volume Method. A source of uncertainty in reproducing laboratory results is that the exact anchoring of the two opposite surfaces is difficult to determine while the stress–permeability relationship is sensitive to the exact positioning. We, therefore, investigate the sensitivity to a mismatch in two scenarios: First, we assess the stress–permeability of a fracture created using two opposing matched surfaces from the rock sample, consequently applying relative shear. Second, we assess the stress–permeability of fractures created by randomly selecting opposing surfaces from that sample. We find that a larger shift leads to a smaller drop in permeability due to applied stress, which is in line with a previous laboratory study. We also find that permeability tends to be higher in fractures with higher roughness within the investigated stress range. Finally, we provide empirical stress–permeability relationships for various relative shears and roughnesses for use in hydro-mechanical studies of fractured geological formations.

The development of an effective vaccine to protect against HIV acquisition will be greatly bolstered by in-depth understanding of the innate and adaptive responses to vaccination. We report here that the efficacy of DNA/ALVAC/gp120/alum vaccines, based on V2-specific antibodies mediating apoptosis of infected cells (V2-ADCC), is complemented by efferocytosis, a cyclic AMP (cAMP)-dependent antiphlogistic engulfment of apoptotic cells by CD14+ monocytes. Central to vaccine efficacy is the engagement of the CCL2/CCR2 axis and tolerogenic dendritic cells producing IL-10 (DC-10). Epigenetic reprogramming in CD14+ cells of the cyclic AMP/CREB pathway and increased systemic levels of miRNA-139-5p, a negative regulator of expression of the cAMP-specific phosphodiesterase PDE4D, correlated with vaccine efficacy. These data posit that efferocytosis, through the prompt and effective removal of apoptotic infected cells, contributes to vaccine efficacy by decreasing inflammation and maintaining tissue homeostasis.

Bulk tank milk (BTM) is regularly used for surveillance on dairy farms for disease conditions such as mastitis and Johne's disease. In this study, we used 16S rRNA sequencing and bait-capture enrichment to characterize the microbiota and resistome of BTM, and investigate potential differences between the cream or pellet fractions. A total of 12 BTM samples were taken from 12 Prince Edward Island dairy farms, in Atlantic Canada, in duplicates. The DNA was analyzed by high-throughput sequencing of the 16S rRNA gene and a suite of antimicrobial resistance (AMR) genes. Target-capture enrichment of AMR genes was conducted before shotgun sequencing. The bioinformatics pipelines QIIME 2 and AMR++ were used for microbiota and resistome analysis, respectively. Differences between microbiotae were evaluated qualitatively with nonmetric multidimensional scaling and quantitatively with permutational ANOVA of UniFrac distances. A total of 47 phyla were present across the BTM samples. Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria were the most abundant phyla. At the genus level, Corynebacterium, Acinetobacter, Lactobacillus, and Turicibacter were the most abundant. There was no significant difference in the Faith's phylogenetic diversity between the cream and pellet fraction. Faith's phylogenetic diversity differed marginally by stall type. There were 10,217 hits across 80 unique AMR genes, with tetracycline resistance being the most common class.

This study sheds new light on the way that group B Streptococcus (GBS) defends itself against oxidative stress in the infected host. The enzyme encoded by the GBS gene npx is an NADH peroxidase that, our study reveals, provides defense against macrophage-derived reactive oxygen stress and facilitates infections of the uterus during pregnancy. This enzyme could represent a tractable target for future treatment strategies against invasive GBS infections.

Streptococcus agalactiae, also known as group B Streptococcus (GBS), is a Gram-positive encapsulated bacterium that colonizes the gastrointestinal tract of 30 to 50% of humans. GBS causes invasive infection during pregnancy that can lead to chorioamnionitis, funisitis, preterm prelabor rupture of membranes (PPROM), preterm birth, neonatal sepsis, and maternal and fetal demise. Upon infecting the host, GBS encounters sentinel innate immune cells, such as macrophages, within reproductive tissues. Once phagocytosed by macrophages, GBS upregulates the expression of the gene

Aflatoxins are carcinogens mainly produced by

Antimicrobial resistance (AMR) is considered a critical threat to public health, and genomic/metagenomic investigations featuring high-throughput analysis of sequence data are increasingly common and important. We previously introduced MEGARes, a comprehensive AMR database with an acyclic hierarchical annotation structure that facilitates high-throughput computational analysis, as well as AMR++, a customized bioinformatic pipeline specifically designed to use MEGARes in high-throughput analysis for characterizing AMR genes (ARGs) in metagenomic sequence data. Here, we present MEGARes v3.0, a comprehensive database of published ARG sequences for antimicrobial drugs, biocides, and metals, and AMR++ v3.0, an update to our customized bioinformatic pipeline for high-throughput analysis of metagenomic data (available at MEGLab.org). Database annotations have been expanded to include information regarding specific genomic locations for single-nucleotide polymorphisms (SNPs) and insertions and/or deletions (indels) when required by specific ARGs for resistance expression, and the updated AMR++ pipeline uses this information to check for presence of resistance-conferring genetic variants in metagenomic sequenced reads. This new information encompasses 337 ARGs, whose resistance-conferring variants could not previously be confirmed in such a manner. In MEGARes 3.0, the nodes of the acyclic hierarchical ontology include 4 antimicrobial compound types, 59 resistance classes, 233 mechanisms and 1448 gene groups that classify the 8733 accessions.

Streptococcus agalactiae, also known as Group BStreptococcus(GBS), is a Gram- positive encapsulated bacterium that colonizes the gastrointestinal tract of 30-50% of humans. GBS causes invasive infection during pregnancy that can lead to chorioamnionitis, funisitis, preterm prelabor rupture of membranes (PPROM), preterm birth, neonatal sepsis, and maternal and fetal demise. Upon infecting the host, GBS encounters sentinel innate immune cells, such as macrophages, within reproductive tissues. Once phagocytosed by macrophages, GBS upregulates expression of the gene,npx, which encodes a NADH peroxidase. GBS mutants with anpxdeletion (Δnpx) are exquisitely sensitive to reactive oxygen stress. Furthermore, we have shown thatnpxis required for GBS survival in both THP-1 and placental macrophages. In anin vivomurine model of ascending GBS vaginal infection during pregnancy,npxis required for invasion of reproductive tissues and is critical for inducing disease progression including PPROM and preterm birth. Reproductive tissue cytokine production was also significantly diminished in Δnpxinfected animals compared to those infected with wild type (WT)-GBS. Complementationin transreversed this phenotype, indicatingnpxis critical for GBS survival and initiation of proinflammatory signaling in the gravid host.

There are no standard prioritization criteria for evaluating thermal energy storage (TES) options for use in integrated energy systems. A framework for proposing, analyzing, and presenting energy s...

Chronic infection with Helicobacter pylori increases risk of gastric diseases including gastric cancer. Despite development of a robust immune response, H. pylori persists in the gastric niche. Progression of gastric inflammation to serious disease outcomes is associated with infection with H. pylori strains which encode the cag Type IV Secretion System (cag T4SS). The cag T4SS is responsible for translocating the oncogenic protein CagA into host cells and inducing pro-inflammatory and carcinogenic signaling cascades. Our previous work demonstrated that nutrient iron modulates the activity of the T4SS and biogenesis of T4SS pili. In response to H. pylori infection, the host produces a variety of antimicrobial molecules, including the iron-binding glycoprotein, lactoferrin. Our work shows that apo-lactoferrin exerts antimicrobial activity against H. pylori under iron-limited conditions, while holo-lactoferrin enhances bacterial growth. Culturing H. pylori in the presence of holo-lactoferrin prior to co-culture with gastric epithelial cells, results in repression of the cag T4SS activity. Concomitantly, a decrease in biogenesis of cag T4SS pili at the host-pathogen interface was observed under these culture conditions by high-resolution electron microscopy analyses. Taken together, these results indicate that acquisition of alternate sources of nutrient iron plays a role in regulating the pro-inflammatory activity of a bacterial secretion system and present novel therapeutic targets for the treatment of H. pylori-related disease.

Background Antimicrobials are used in food-producing animals for purposes of preventing, controlling, and/or treating infections. In swine, a major driver of antimicrobial use is porcine reproductive and respiratory syndrome (PRRS), which is caused by a virus that predisposes infected animals to secondary bacterial infections. Numerous antimicrobial protocols are used to treat PRRS, but we have little insight into how these treatment schemes impact antimicrobial resistance (AMR) dynamics within the fecal microbiome of commercial swine. The aim of this study was to determine whether different PRRS-relevant antimicrobial treatment protocols were associated with differences in the fecal microbiome and resistome of growing pigs. To accomplish this, we used a metagenomics approach to characterize and compare the longitudinal wean-to-market resistome and microbiome of pigs challenged with PRRS virus and then exposed to different antimicrobial treatments, and a group of control pigs not challenged with PRRS virus and having minimal antimicrobial exposure. Genomic DNA was extracted from pen-level composite fecal samples from each treatment group and subjected to metagenomic sequencing and microbiome-resistome bioinformatic and statistical analysis. Microbiome-resistome profiles were compared over time and between treatment groups. Results Fecal microbiome and resistome compositions both changed significantly over time, with a dramatic and stereotypic shift between weaning and 9 days post-weaning (dpw). Antimicrobial resistance gene (ARG) richness and diversity were significantly higher at earlier time points, while microbiome richness and diversity were significantly lower. The post-weaning shift was characterized by transition from a Bacteroides-dominated enterotype to Lactobacillus- and Streptococcus-dominated enterotypes. Both the microbiome and resistome stabilized by 44 dpw, at which point the trajectory of microbiome-resistome maturation began to diverge slightly between the treatment groups, potentially due to physical clustering of the pigs. Challenge with PRRS virus seemed to correspond to the re-appearance of many very rare and low-abundance ARGs within the feces of challenged pigs. Despite very different antimicrobial exposures after challenge with PRRS virus, resistome composition remained largely similar between the treatment groups. Differences in ARG abundance between the groups were mostly driven by temporal changes in abundance that occurred prior to antimicrobial exposures, with the exception of ermG, which increased in the feces of treated pigs, and was significantly more abundant in the feces of these pigs compared to the pigs that did not receive post-PRRS antimicrobials. Conclusions The fecal microbiome-resistome of growing pigs exhibited a stereotypic trajectory driven largely by weaning and physiologic aging of the pigs. Events such as viral illness, antimicrobial exposures, and physical grouping of the pigs exerted significant yet relatively minor influence over this trajectory. Therefore, the AMR profile of market-age pigs is the culmination of the life history of the individual pigs and the populations to which they belong. Disease status alone may be a significant driver of AMR in market-age pigs, and understanding the interaction between disease processes and antimicrobial exposures on the swine microbiome-resistome is crucial to developing effective, robust, and reproducible interventions to control AMR.

Histone modifications alter numerous cornerstone processes in eukaryotes, including metabolism, physiology, and immunity. Numerous bacterial pathogens can alter expression of host-derived sirtuins to deacetylate histones in order to promote infection, yet, a bacterial-derived sirtuin has yet to be investigated to deacetylate host histones. Using Campylobacter jejuni, the leading cause of bacterial-derived gastroenteritis, we found a secreted sirtuin, SliP, which binds to and deacetylates neutrophil histones. We found neutrophil activation and extrusion of neutrophil extracellular traps was SliP dependent, whereby sliP mutants are unable to activate neutrophils or promote NETosis. Leveraging the mouse model of campylobacteriosis, we further demonstrate the sliP mutant can efficiently infect IL-10-/- mice, but induction of proinflammatory cytokine production and gastrointestinal pathology is SliP-dependent. In conclusion, we investigate a unique bacterial effector which targets host histones and is responsible for the inflammatory response and tissue pathology observed during campylobacteriosis.HighlightsC. jejuni encodes a secreted effector, SliP, which functions as a canonical sirtuinSliP binds to and deacetylates neutrophil histone H3 during bacterial infectionC. jejuni-induced neutrophil activation and NETosis are SliP-dependentInflammation and tissue pathology during C. jejuni infection is SliP-dependent

Teaching mathematics involves a variety of techniques and approaches in order to reach students’ academic needs in a way that aids them in achieving at the level required by state standards. One of the ways that educators are meeting the needs of their students is through using computer-based programs. In this study, 17 fifth grade students were placed into two groups and assigned computer-based programs. One program, MobyMax, offered students scaffolding measures to aid in concept development. The other program, IXL, offered students detailed feedback in response to their answer submissions. This study was designed to determine the impact of the features of the two computer-based programs on student achievement through problem solving and their level of motivation. Students in both groups experienced gains in problem solving ability on average. Time spent on the program did not appear to be a contributing factor to gain score for problem solving. And student motivation showed little change throughout using either computer-based program.

Background The global COVID-19 pandemic has placed tremendous physical and mental strain on the US healthcare system. Studies examining the effects of outbreaks have demonstrated both an increased prevalence and long-term development of Post-Traumatic Stress Disorder (PTSD) symptoms in healthcare providers. We sought to assess the impact of the COVID-19 pandemic on the psychological well-being of medical providers, medical trainees, and administrators at a large academic center to identify stressors and moderators to guide future mental health and hospital-system interventions. Methods A 42-item survey examining specific stressors, grit, and resilience was widely distributed to physicians, residents, fellows, and administrators a large academic institution for departmental distribution. Survey results were analyzed using descriptive statistics, ANOVA, and multivariate linear regressions. A p-value, Highlights • Healthcare providers are experiencing higher levels of stress during the COVID-19 pandemic. • Healthcare providers have high resilience, which is protective against stress and other negative psychological factors resulting from this pandemic. • Future research should evaluate the efficacy of mental skills and resilience training in frontline workers to reduce symptoms of PTSD in future times of global crisis.

The American Board of Surgery (ABS) has required Fundamentals of Endoscopic Surgery (FES) certification for general surgery applicants since 2018. Flexible Endoscopy Curriculum (FEC) completion is recommended prior to taking the FES exam. The objective of the study was to determine if FEC completion prepares individuals to pass the FES manual skills test.Participants included first-attempt FES examinees from June 2014 to February 2019. De-identified data were reviewed, Self-reported data included gender, PGY, glove size, upper (UE) and lower (LE) endoscopy experience, simulation training time, and participation in an endoscopy rotation (ER). FES skills exam performance was reported by FES staff. Those completing all vs. none of the FEC were compared.Of 2023 participants identified, 809 (40.0%) reported completion of all FEC components, 1053 (52.1%) completed of some, and 161 (8.0%) completed none. Men and candidates taking FES later in residency were more likely to complete all FEC requirements (p = 0.002, p 0.001). FES pass rates were higher for those who completed all FEC components compared to those who completed none (88.4% vs 72.7%, p 0.001). On logistic regression analysis, completion of all components (OR 2.3, 95% CI 1.5-3.7, p 0.001) and male gender (OR 3.1, 95% CI 1.7-5.7, p 0.001) were predictors of passing, while glove size (OR 1.5, 95% CI 1.0-2.5, p = 0.08), simulator time (OR 1.1, 95% CI 0.9-1.4, p = 0.37) and PGY were not (OR 1.1, 95% CI 0.9-1.4, p = 0.38). On multivariate analysis controlling for glove size and gender, completion of all FEC components was still associated with a higher likelihood of passing the FES skills exam (OR 1.6, 95% CI 1.2-2.1, p 0.001).Completion of FEC is strongly associated with passing the FES skills test. This study supports the ABS recommendation for completion of FEC prior to taking the FES skills test.

Streptococcus species are common causes of human infection. These Gram-positive, encapsulated bacterial pathogens infect diverse anatomic spaces, leading to infections including skin and soft tissue infection, endocarditis, pneumonia, meningitis, sinusitis, otitis media, chorioamnionitis, sepsis, and even death. Risk for streptococcal infection is highest in low- and middle-income countries where micronutrient deficiency is common. Epidemiological data reveal that vitamin D deficiency is associated with enhanced risk of streptococcal infection and cognate disease outcomes. Additionally, vitamin D improves antibacterial defenses by stimulating innate immune processes such as phagocytosis and enhancing production of reactive oxygen species (oxidative burst) and antimicrobial peptides (including cathelicidin and lactoferrin), which are important for efficient killing of bacteria. This review presents the most recent published work that studies interactions between the micronutrient vitamin D, the host immune system, and pathogenic streptococci as well as comparisons with other relevant infection models.

Introduction: Uterine prolapse is the descent of the uterus into the vagina or out of the vagina as a result of the failure of the ligament as a pelvic support. Uterine prolapse has multifactorial risk factors, but in every case of uterine prolapse, weakness is found in the pelvic floor supporting tissues, including the sacrouterine ligament. Childbirth is direct trauma that cause damage and weakness of levaor ani muscle, which leads to stretch of sacrouterine ligament that plays important role in maintaining uterus in its normal position. The main structure of the sacrouterine ligament consists of cells and extracellular matrix such as collagen, elastin, glycoproteins (fibronectin, tenascin, link protein, fibromodulin and dan osteopontin) and proteoglycans (agrecan, versican, biglican, dan perlecan). Tenascin is a major oligomeric glycoprotein found in the extracellular matrix. Tenascin has an important role not only during development but also when there are pathological conditions in adulthood such as tissue injury and tumorigenesis. Based on the current research, there are four tenascin groups, that are: tenascin-C, tenascin-R, tenascin-X, tenascin-Y and tenascin-W. If there is an expression of tenascin-C disturbance  in the sacrouterine ligament, it will cause uterine prolapse. The purpose of this study was to prove the high expression of tenascin-C in the sacrouterine ligament as a risk factor for stage III-IV uterine prolapse.Method: This research is an observational study with case control design. Forty four cases was included in this study. Twenty-two cases of III-IV degree uterine prolapse as study group and another 22 non-prolapse cases as a control group. This research was carried out in Sanglah General Hospital and Patobiology Laboratory of the Faculty of Veterinary Medicine UNUD. Samples were taken from the sacrouterine ligament of grade III-IV uterine prolapse patients and uterine non-prolapse patients, that had been performed total hysterectomy.Result: The results showed that high tenascin-C expression was a risk factor for stage III - IV uterine prolapse by 5.9 times (OR = 5.9; IK 95% = 1.59-22.32; p = 0.006).Conclusion: It can be concluded that high expression of tenascin-C in the sacrouterine ligament is a risk factor of III-IV degree uterine prolapse.  Latar Belakang: Prolaps uterus adalah turunnya uterus ke dalam liang vagina atau keluar liang vagina sebagai akibat gagalnya ligmentum penyokong dasar panggul. Prolaps uterus memiliki faktor risiko yang bersifat multifaktorial, namun pada setiap kasus prolaps uterus, selalu ditemukan kelemahan pada jaringan penyangga dasar panggul, termasuk ligamentum sakrouterina. Trauma langsung pada jalan lahir yang mengakibatkan kerusakan dan kelemahan otot levaor ani sehingga mengakibatkan ligamentum sakrouterina meregang untuk mempertahankan uterus dalam posisi normal. Struktur utama ligamen sakrouterina terdiri dari sel dan matriks ekstraseluler seperti kolagen, elastin, glikoprotein (fibronectin, tenascin, link protein, fibromodulin ) dan proteoglikan (agrecan, versican, biglican, dan perlecan). Tenascin merupakan suatu glikoprotein oligomerik utama yang terdapat pada matriks ekstraseluler. Tenascin memiliki peranan penting tidak hanya pada masa perkembangan tetapi juga saat terjadi kondisi patologis pada usia dewasa seperti cedera jaringan dan tumorigenesis. Berdasarkan penelitian saat ini, dikenal empat kelompok tenascin yaitu : tenascin-C, tenascin-R, tenascin-X, tenascin-Y dan tenascin-W. Apabila terjadi gangguan dalam ekspresi tenascin-C pada ligamentum sakrouterina akan menyebabkan terjadinya prolaps uterus. Tujuan penelitian ini adalah untuk membuktikan ekspresi tenascin-C yang tinggi pada ligamentum sakrouterina sebagai faktor risiko terjadinya prolaps uterus derajat III-IV.Metode: Penelitian ini merupakan rancangan observasional dengan kasus kontrol. Terdapat 22 kasus prolaps uterus derajat III-IV sebagai kelompok kasus dan 22 kasus non prolaps sebagai kelompok kontrol. Penelitian ini dikerjakan di RSUP Sanglah dan Laboratorium Patobiologi FKH UNUD. Sampel diambil dari ligamentum sakrouterina pasien prolaps uterus derajat III-IV dan non-prolaps uterus yang telah dilakukan histerektomi total.Hasil: Hasil penelitian didapatkan bahwa ekspresi tenacin-C yang tinggi merupakan faktor risiko terjadinya prolaps uterus derajat III - IV sebesar 5,9 kali (OR =5,9; IK 95% =1,59-22,32; p =0,006).Simpulan: Sehingga dapat disimpulkan bahwa ekspresi tenascin-C yang tinggi pada ligamentum sakrouterina sebagai faktor risiko terjadinya prolaps uterus derajat III-IV.

Flow modelling challenges in fractured reservoirs have led to the development of many simulation methods. It is often unclear which method should be employed. High-resolution discrete fracture and matrix (DFM) studies on small-scale representative models allow us to identify dominant physical processes influencing flow. We propose a workflow that utilizes DFM studies to characterize subsurface flow dynamics. The improved understanding facilitates the selection of an appropriate method for large-scale simulations. Validation of the workflow was performed via application on a gas reservoir represented using an embedded discrete fracture model, followed by the comparison of results obtained from hybrid and dual-porosity representations against fully explicit simulations. The comparisons ascertain that the high-resolution small-scale DFM studies lead to a more accurate upscaled model for full field simulations. Additionally, we find that hybrid implicit–explicit representations of fractures generally outperform pure continuum-based models.

Streptococcal species are gram positive bacteria responsible for a variety of disease outcomes including pneumonia, meningitis, endocarditis, erysipelas, necrotizing fasciitis, periodontitis, skin and soft tissue infections, chorioamnionitis, premature rupture of membranes, preterm birth, and neonatal sepsis. In response to streptococcal infections, the host innate immune system deploys a repertoire of antimicrobial and immune modulating molecules. One important molecule that is produced in response to streptococcal infections is lactoferrin. Lactoferrin has antimicrobial properties including the ability to bind iron with high affinity and sequester this important nutrient from an invading pathogen. Additionally, lactoferrin has the capacity to alter the host inflammatory response and contribute to disease outcome. This review presents the most recent published work that studies the interaction between the host innate immune protein lactoferrin and the invading pathogen, Streptococcus.

We have previously shown that augmenting orthogonal matching pursuit (OMP) with an additional step in the identification stage of each pursuit iteration yields improved $k$ -sparse reconstruction and denoising performance relative to baseline OMP. At each iteration a “path” or geodesic, is generated between the two dictionary atoms that are most correlated with the residual and from this path a new atom that has a greater correlation to the residual than either of the two bracketing atoms is selected. Here, we provide new computational results illustrating improvements in sparse coding and denoising on canonical datasets using both learned and structured dictionaries. The two methods of constructing a path are investigated for each dictionary type: the Euclidean geodesic formed by a linear combination of the two atoms and the 2-Wasserstein geodesic corresponding to the optimal transport map between the atoms. We prove here the existence of a higher-correlation atom in the Euclidean case under assumptions on the two bracketing atoms and introduce algorithmic modifications to improve the likelihood that the bracketing atoms meet those conditions. Although, we demonstrate our augmentation on OMP alone, in general it may be applied to any reconstruction algorithm that relies on the selection and sorting of high-similarity atoms during an analysis or identification phase.

Human T cell leukemia virus type 1 (HTLV-1) persists in the host despite a vigorous immune response that includes cytotoxic T cells (CTL) and natural killer (NK) cells, suggesting the virus has developed effective mechanisms to counteract host immune surveillance. We recently showed that in vitro treatment of HTLV-1-infected cells with the drug pomalidomide (Pom) increases surface expression of MHC-I, ICAM-1, and B7-2, and significantly increases the susceptibility of HTLV-1-infected cells to NK and CTL killing, which is dependent on viral orf-I expression. We reasoned that by restoring cell surface expression of these molecules, Pom treatment has the potential to reduce virus burden by rendering infected cells susceptible to NK and CTL killing. We used the rhesus macaque model to determine if Pom treatment of infected individuals activates the host immune system and allows recognition and clearance of HTLV-1-infected cells. We administered Pom (0.2 mg/kg) orally to four HTLV-1-infected macaques over a 24 day period and collected blood, urine, and bone marrow samples throughout the study. Pom treatment caused immune activation in all four animals and a marked increase in proliferating CD4+, CD8+, and NK cells as measured by Ki-67+ cells. Activation markers HLA-DR, CD11b, and CD69 also increased during treatment. While we detected an increased frequency of cells with a memory CD8+ phenotype, we also found an increased frequency of cells with a Treg-like phenotype. Concomitant with immune activation, the frequency of detection of viral DNA and the HTLV-1-specific humoral response increased as well. In 3 of 4 animals, Pom treatment resulted in increased antibodies to HTLV-1 antigens as measured by western blot and p24Gag ELISA. Consistent with Pom inducing immune and HTLV-1 activation, we measured elevated leukotrienes LTB4 and LTE4 in the urine of all animals. Despite an increase in plasma LTB4, no significant changes in plasma cytokine/chemokine levels were detected. In all cases, however, cellular populations, LTB4, and LTE4 decreased to baseline or lower levels 2 weeks after cessation of treatment. These results indicated that Pom treatment induces a transient HTLV-1-specific immune activation in infected individuals, but also suggest Pom may not be effective as a single-agent therapeutic.

In recent years, nanomechanics has evolved into a mature field, with wide-ranging impact from sensing applications to fundamental physics, and it has now reached a stage which enables the fabrication and study of ever more elaborate devices. This has led to the emergence of arrays of coupled nanomechanical resonators as a promising field of research, serving as model systems to study collective dynamical phenomena such as synchronization or topological transport. From a general point of view, the arrays investigated so far represent scalar fields on a lattice. Moving to a scenario where these could be extended to vector fields would unlock a whole host of conceptually interesting additional phenomena, including the physics of polarization patterns in wave fields and their associated topology. Here we introduce a new platform, a two-dimensional array of coupled nanomechanical pillar resonators, whose orthogonal vibration directions encode a mechanical polarization degree of freedom. We demonstrate direct optical imaging of the collective dynamics, enabling us to analyze the emerging polarization patterns and follow their evolution with drive frequency., 7 pages main text, 5 figures, 11 pages appendices

It is often said that a deep learning model is "invariant" to some specific type of transformation. However, what is meant by this statement strongly depends on the context in which it is made. In this paper we explore the nature of invariance and equivariance of deep learning models with the goal of better understanding the ways in which they actually capture these concepts on a formal level. We introduce a family of invariance and equivariance metrics that allows us to quantify these properties in a way that disentangles them from other metrics such as loss or accuracy. We use our metrics to better understand the two most popular methods used to build invariance into networks: data augmentation and equivariant layers. We draw a range of conclusions about invariance and equivariance in deep learning models, ranging from whether initializing a model with pretrained weights has an effect on a trained model's invariance, to the extent to which invariance learned via training can generalize to out-of-distribution data., Comment: To appear at NeurIPS 2022

Background: Completion of the Fundamentals of Laparoscopic (FLS) and Endoscopic Surgery (FES) Programs has been required by the American Board of Surgery (ABS) for general surgery certification for several years. While validity evidence exists to support these assessments as high stakes examinations, retrospective studies on pass rates have noticed an alarming trend in gender-based performance discrepancy, with men consistently outperforming women. Purpose: The purpose of this study was to investigate the following questions: 1) What is the relationship between demographic variables and performance of endosurgical skills? 2) What is the relationship between visuospatial aptitude and performance? 3) What is the underlying etiology of gender-based discrepancy? 4) Does the robotic platform minimize gender-based performance discrepancy? Methods: Sixty-nine novice participants completed a visuospatial aptitude assessment and a series of tasks on an endoscopic simulator, robotic simulator, laparoscopic box trainer, and robotic dome trainer. Bivariate analyses were performed to analyze the relationship between performance and demographic variables, which guided subsequent multivariate linear regression analyses. Results: While performance on the laparoscopic tasks was less uniform, men outperformed women on all 3 FES tasks (18.1 points, p < 0.001 for FES Navigation, 19.9 points, p < 0.001 for FES Retroflexion, and 18.3 points, p < 0.001 for FES Tool Manipulation). Men also scored higher in the visuospatial aptitude assessment by 4.7 points (p < 0.001). After controlling for gender, visuospatial aptitude, the interaction between gender and visuospatial aptitude, glove size, hand dominance, height, ethnicity and ergonomics, visuospatial aptitude remained the only significant variable associated with all three FES tasks (Table 1). There was also no gender-related difference with regards to the robotic simulator or dome trainer, suggesting that when known differences between genders relating to grip strength and physical motor behavior are mitigated through an ergonomically unbiased platform, performance differences dissipate. Discussion: Our study supports the conclusion that previously observed gender differences in surgical performance are the result of visuospatial aptitude difference, not gender, and perpetuating the false belief that men are inherently better than women in surgical domains further amplifies the stereotype threat women in surgery face.