Search

Abstract Introduction Polycystic ovary syndrome (PCOS) is a common endocrine pathology in women. In addition to infertility, women with PCOS have metabolic dysregulation which predisposes them to Type 2 diabetes, cardiovascular disease and non‐alcoholic fatty liver disease. Moreover, women with PCOS have changes in their gut microbial community that may be indicative of dysbiosis. While hyperandrogenism is associated with both the development of metabolic dysfunction and gut dysbiosis in females, the mechanisms involved are not well understood. Methods We used dihydrotestosterone (DHT) and ovariectomy (OVX) mouse models coupled with metabolic assessments and 16S rRNA gene sequencing to explore the contributions of hyperandrogenism and oestrogen deficiency to the development of insulin resistance and gut microbial dysbiosis in pubertal female mice. Results We demonstrated that, while DHT treatment or OVX alone were insufficient to induce insulin resistance during the pubertal‐to‐adult transition, combining OVX with DHT resulted in insulin resistance similar to that observed in letrozole‐treated mice with elevated testosterone and decreased oestrogen levels. In addition, our results showed that OVX and DHT in combination resulted in a distinct shift in the gut microbiome compared to DHT or OVX alone, suggesting that the substantial metabolic dysregulation occurring in the OVX + DHT model was accompanied by unique changes in the abundances of gut bacteria including S24‐7, Rikenellaceae and Mucispirillum schaedleri. Conclusions While hyperandrogenism plays an important role in the development of metabolic dysregulation in female mice, our results indicate that investigation into additional factors influencing insulin resistance and the gut microbiome during the pubertal‐to‐adult transition could provide additional insight into the pathophysiology of PCOS.

Humans can quickly infer when someone’s body movements are meant to be communicative. Here, the authors show that this capacity is underpinned by an expectation that communicative actions will efficiently reveal that they lack an external goal.

Abstract Background Despite the recent increase in HIV infections among adolescents, little is known about their HIV knowledge and perceptions. This study, therefore, sought to examine the factors associated with comprehensive HIV knowledge, stigma, and HIV risk perceptions among young adolescents aged 10–14 years in Akwa Ibom State, Nigeria. Additionally, consenting parents and assenting young adolescents were tested for HIV. Methods We used cross-sectional data from the 2017 Akwa Ibom AIDS Indicator Survey to analyze comprehensive HIV knowledge, stigma, and HIV risk perceptions among young adolescents. Demographic characteristics of young adolescents were summarized using descriptive statistics. Chi-square test (or Fisher’s exact test in cases of small subgroup sample sizes) was used to elicit associations between demographics and study outcomes. Separate multivariable logistic regression models were then conducted to determine associations with the study outcomes. Sampling weights were calculated in order to adjust for the sample design. P-values less than 0.05 were considered to be significant. Results A total of 1818 young adolescents were interviewed. The survey highlighted significant low levels of comprehensive HIV knowledge (9.4%) among young adolescents. Adolescent-parent discussions [AOR = 2.19, 95% C.I (1.10–4.38), p = 0.03], schools as sources of HIV information [AOR = 8.06, 95% C.I (1.70–38.33), p

The aim of this paper is to analyze how the governance of an enterprise blockchain ecosystem changes as it matures and increases in size. A review of the literature serves to identify five behavioral drivers of governance, which appear to affect the long-term viability of a blockchain ecosystem: access rights, decision rights, incentives, accountability, and conflict resolution. We subsequently report the findings from a comparative case study of how three large blockchain ecosystems implemented various governance mechanisms to exploit and modify the five behavioral drivers over time. Based on twenty-six interviews and approximately 200 h of participant observations, we propose an analytical framework that consists of three distinctive stages in the life cycle of a blockchain ecosystem. Each stage is characterized by an intricate relationship between off-chain and on-chain governance mechanisms. Based on these findings, various recommendations are provided to increase the long-term viability of blockchain ecosystems.

OBJECTIVES/GOALS: To describe a study to develop, test, and collect implementation data on a youth-led hypertension (HTN) education digital intervention that acts as an electronic tool to guide youth through learning and then teaching adults on how to achieve better HTN control. Adults with uncontrolled HTN are recruited from a New Jersey emergency department (ED). METHODS/STUDY POPULATION: Adults with HTN and youth (15-18 years) participate in a remote user-centered design session focus group to provide input in the development of the youth-led HTN education digital intervention. 100 adult ED patients with uncontrolled HTN (blood pressure (BP) ≥130/80 mm Hg) who live with a youth (15-18 years) and the youth themselves are recruited for a randomized control trial (RCT). The adult-youth dyad is randomized to one of two arms, each a 6-week program with youth earning a digital badge: 1) intervention- youth-led HTN education with the adult, or 2) control- youth learn life skills (such as job readiness/resume building). Implementation metrics are collected through a post-intervention survey and qualitative interviews on the digital badge intervention including acceptability, feasibility, and fidelity. RESULTS/ANTICIPATED RESULTS: We completed two youth focus groups (total of 8 participants) and data collection is ongoing. Youth have shown great interest in the intervention prototype and thought their peers would find it acceptable. They suggested additions to nutrition education activities, such as adding a sodium tracker and examples of high sodium foods. For the RCT, the primary study outcome is adult BP change (from baseline to 1 week and 2-months post-intervention), with secondary outcomes of HTN knowledge and youth self-efficacy. We anticipate that intervention arm adults will have a more significant decrease in BP than control arm adults. We also expect that HTN knowledge and youth self-efficacy will be higher for the intervention arm. Implementation data collected will allow for improvements to future renditions of the intervention. DISCUSSION/SIGNIFICANCE: Bringing health education home while simultaneously empowering youth is an innovative technology-driven model for improving BP for patients with uncontrolled HTN who may lack access to care. Outcomes of this project will result in a scalable and easily adoptable model to reach an otherwise difficult to reach adult population.

A 9-year-old spayed female German shepherd mixed-breed dog presented for seizures. Magnetic resonance imaging revealed an irregularly marginated intraparenchymal cerebral mass. Microscopic examination of brain tissue collected postmortem demonstrated perivascular whorling and interwoven bundles of spindle-shaped cells. On immunohistochemistry, the tumor cells tested positive for vimentin and negative for factor VIII-related antigen, CD18, CD45, CD3, CD20, GFAP, S-100, and desmin. Immunohistochemistry results, in combination with histopathologic morphology, were suggestive of a perivascular wall tumor. To the authors’ knowledge, this is the first case report to utilize both histopathology and immunohistochemistry to describe a perivascular wall tumor in the brain of a dog.

Abstract Long-term reconstituting haematopoietic stem cells (LT-HSCs) are used to treat blood disorders via stem cell transplantation. The very low abundance of LT-HSCs and their rapid differentiation during in vitro culture hinders their clinical utility. Previous developments using stromal feeder layers, defined media cocktails, and bioengineering have enabled HSC expansion in culture, but of mostly short-term HSCs and progenitor populations at the expense of naive LT-HSCs. Here, we report the creation of a bioengineered LT-HSC maintenance niche that recreates physiological extracellular matrix organisation, using soft collagen type-I hydrogels to drive nestin expression in perivascular stromal cells (PerSCs). We demonstrate that nestin, which is expressed by HSC-supportive bone marrow stromal cells, is cytoprotective and, via regulation of metabolism, is important for HIF-1α expression in PerSCs. When CD34+ve HSCs were added to the bioengineered niches comprising nestin/HIF-1α expressing PerSCs, LT-HSC numbers were maintained with normal clonal and in vivo reconstitution potential, without media supplementation. We provide proof-of-concept that our bioengineered niches can support the survival of CRISPR edited HSCs. Successful editing of LT-HSCs ex vivo can have potential impact on the treatment of blood disorders.

The amount of SARS-CoV-2 in a sample is often measured using Ct values. However, the same Ct value may correspond to different viral loads on different platforms and assays, making them difficult to compare from study to study. To address this problem, we developed ct2vl, a Python package that converts Ct values to viral loads for any RT-qPCR assay/platform. The method is novel in that it is based on determining the maximum PCR replication efficiency, as opposed to fitting a sigmoid (S-shaped) curve relating signal to cycle number. We calibrated ct2vl on two FDA-approved platforms and validated its performance using reference-standard material, including sensitivity analysis. We found that ct2vl-predicted viral loads were highly accurate across five orders of magnitude, with 1.6-fold median error (for comparison, viral loads in clinical samples vary over 10 orders of magnitude). The package has 100% test coverage. We describe installation and usage both from the Unix command-line and from interactive Python environments. ct2vl is freely available via the Python Package Index (PyPI). It facilitates conversion of Ct values to viral loads for clinical investigators, basic researchers, and test developers for any RT-qPCR platform. It thus facilitates comparison among the many quantitative studies of SARS-CoV-2 by helping render observations in a natural, universal unit of measure.

Regulation of interleukin-2 (IL-2) gene expression by the p50 and p65 subunits of the DNA binding protein NF-κB was studied in nontransformed [CD4.sup.+] T lymphocyte clones. A homodimeric complex of the NF-κB p50 subunit was found in resting T cells. The amount of p50-p50 complex decreased after full antigenic stimulation, whereasa the amount of the NF-κB p50-p65 heterodimer was increased. Increased expression of the IL-2 gene and activity of the IL-2 κB DNA binding site correlated with a decrease in the p50-p50 complex. Overexpression of p50 repressed IL-2 promoter expression. The switch from p50-p50 to p50-p65 complexes depended on a protein that caused sequestration of the p50-p50 complex in the nucleus., Tumor cell lines have proven vital to the study of gene regulation because they are easily grown and manipulated. However, nontransformed T cells exhibit biological characteristics that are not manifested [...]

The article presents a case study of a 1.5-year-old 16-kg spayed female Australian Cattle Dog was evaluated at a veterinary teaching hospital because of sudden-onset paraparesis that had progressed to paraplegia over the past three days. It mentions that differential diagnoses for acute deteriorating paraparesis-paraplegia in a dog included trauma with associated instability and inflammatory (immune-mediated myelitis).

Objectives: The sexually transmitted infections, Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV), and Mycoplasma genitalium (MG), have similar risk factors and symptoms, supporting use of a quadruplex test as an efficient diagnostic modality.We assessed the clinical and analytical performance of the Abbott Alinity m STI assay to detect these pathogens. Design and methods: Urine and genital swabs from 142 patient samples were tested from an adult outpatient population in the Northeast United States. The positive and negative percent agreement for CT, NG, and TV were determined by comparison with the Hologic Panther Aptima assay. The analytical sensitivity was determined through serial dilution of standards for CT, NG, TV, and MG in negative urine and swab matrix. Results: The positive and negative percent agreement of the Alinity m assay in comparison with the Hologic Panther Aptima assay were, respectively: CT [100.0% (90.6–100.0%) and 99.1% (94.8–100.0%)], NG [100.0% (89.6–100.0%) and 99.1% (94.9–100.0%)]; and TV [96.3% (81.7–99.8%) and 99.1% (95.2–100.0%)]. The limits of detection in urine and swab matrix were, respectively: CT ≤ 5, ≤1; NG ≤ 5, ≤5; TV ≤ 0.5, ≤0.5; and MG ≤ 500, ≤250 genome copies/mL. Conclusions: The Alinity m assay demonstrated excellent performance characteristics and identifies CT, NG, and TV accurately compared with a well-established comparator.

Human neuroimaging studies have revealed a dedicated cortical system for visual scene processing. But what is a “scene”? Here, we use a stimulus-driven approach to identify a stimulus feature that selectively drives cortical scene processing. Specifically, using fMRI data from BOLD5000, we examined the images that elicited the greatest response in the cortical scene processing system, and found that there is a common “vertical luminance gradient” (VLG), with the top half of a scene image brighter than the bottom half; moreover, across the entire set of images, VLG systematically increases with the neural response in the scene-selective regions (Study 1). Thus, we hypothesized that VLG is a stimulus feature that selectively engages cortical scene processing, and directly tested the role of VLG in driving cortical scene selectivity using tightly controlled VLG stimuli (Study 2). Consistent with our hypothesis, we found that the scene-selective cortical regions—but not an object-selective region or early visual cortex—responded significantly more to images of VLG over control stimuli with minimal VLG. Interestingly, such selectivity was also found for images with an “inverted” VLG, resembling the luminance gradient in night scenes. Finally, we also tested the behavioral relevance of VLG for visual scene recognition (Study 3); we found that participants even categorized tightly controlled stimuli of both upright and inverted VLG to be a place more than an object, indicating that VLG is also used for behavioral scene recognition. Taken together, these results reveal that VLG is a stimulus feature that selectively engages cortical scene processing, and provide evidence for a recent proposal that visual scenes can be characterized by a set of common and unique visual features.

A personal narrative is presented which explores the author's experience as a medical student with major depressive disorder, with topics mentioned such as the challenges of medical school, nervous breakdown she experienced two months into her second year, and a suicide committed by her classmate at the end of their third year of medical school.

ABSTRACT The continued need for molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the potential for self-collected saliva as an alternative to nasopharyngeal (NP) swabs for sample acquisition led us to compare saliva to NP swabs in an outpatient setting without restrictions to avoid food, drink, smoking, or tooth-brushing. A total of 385 pairs of NP and saliva specimens were obtained, the majority from individuals presenting for initial evaluation, and were tested on two high-sensitivity reverse transcriptase PCR (RT-PCR) platforms, the Abbott m2000 and Abbott Alinity m (both with limits of detection [LoD] of 100 copies of viral RNA/ml). Concordance between saliva and NP swabs was excellent overall (Cohen’s κ = 0.93) for both initial and follow-up testing, for both platforms, and for specimens treated with guanidinium transport medium as preservative as well as for untreated saliva (κ = 0.88 to 0.95). Viral loads were on average 16× higher in NP specimens than saliva specimens, suggesting that only the relatively small fraction of outpatients (∼8% in this study) who present with very low viral loads (

Despite over two decades of research on the neural mechanisms underlying human visual scene, or place, processing, it remains unknown what exactly a “scene” is. Intuitively, we are always inside a scene, while interacting with the outside of objects. Hence, we hypothesize that one diagnostic feature of a scene may be concavity, portraying “inside”, and predict that if concavity is a scene-diagnostic feature, then: 1) images that depict concavity, even non-scene images (e.g., the “inside” of an object – or concave object), will be behaviorally categorized as scenes more often than those that depict convexity, and 2) the cortical scene-processing system will respond more to concave images than to convex images. As predicted, participants categorized concave objects as scenes more often than convex objects, and, using functional magnetic resonance imaging (fMRI), two scene-selective cortical regions (the parahippocampal place area, PPA, and the occipital place area, OPA) responded significantly more to concave than convex objects. Surprisingly, we found no behavioral or neural differences between images of concave versus convex buildings. However, in a follow-up experiment, using tightly-controlled images, we unmasked a selective sensitivity to concavity over convexity of scene boundaries (i.e., walls) in PPA and OPA. Furthermore, we found that even highly impoverished line drawings of concave shapes are behaviorally categorized as scenes more often than convex shapes. Together, these results provide converging behavioral and neural evidence that concavity is a diagnostic feature of visual scenes.

Rapid change in business environment poses threat to business survival. It is crucial to examine the core of business sustainability. This paper proposes changeless factors in response to today’s business environment. Specifically, it addresses (1) the people factor (2) the purpose factor and (3) the principle factor as the pillars through which an organization finds its stability in the sea of business change. This paper demonstrates the unchanged factors to ensure business sustainability and to achieve long term objectives. After mapping the conceptual model, the paper devotes particular attention to conceptualizing the changeless cores of business. This research contributes practical insights for managers to further understand the cores of business sustainability. Specifically, it will assist managers to have clear goals in making decisions and managing change to enhance competitiveness in the business environment.

A 10-fold improvement in the signal-to-noise (S/N) ratio of an optically encoded silica particle-based immunoassay was achieved through incorporating a protein resistant poly(ethylene glycol) (PEG) surface layer and optimizing antibody immobilization conditions. PEG was activated using 2,2,2-trifluoroethanesulfonyl chloride (tresyl) and required a minimum reaction time of 1.5 h. The activated PEG had a reactive half-life of approximately 5 h when stored in acidified dimethyl sulfoxide (DMSO). By increasing the protein incubation time and concentration, a maximum antibody loading on the particle surface of 1.6 × 10−2molecules per nm2was achieved. The assay S/N ratio was assessed using a multiplexed multicomponent optically encoded species-specific immunoassay. Encoded particles were covalently grafted or nonspecifically coated with either bovine or mouse IgG for the simultaneous detection of complementary anti-IgG “target” or uncomplementary anti-IgG “noise”. The versatility and potential as a serum-based assay platform was demonstrated by immobilizing either a polyclonal antibody or an engineered single-chain variable fragment (scFv) capture probe on particles for the detection of the ovarian cancer biomarker, mesothelin (MSLN). The MLSN antigen was spiked into PBS buffer or 50% human serum. Both capture probe orientations, and media conditions showed similar low level detection limits of 5 ng/mL; however, a 40% decrease in maximum signal intensity was observed for assays run in 50% serum. [ABSTRACT FROM AUTHOR]

This study presents the use of flow cytometry as a high-throughput quantifiable technique to study multicomponent adsorption interactions between proteins and surfaces. Flow cytometry offers the advantage of high-throughput analysis of multiple parameters on a very small sampling scale. This enables flow cytometry to distinguish between individual adsorbent particles and adsorbate components within a suspension. As a proof of concept study, the adsorption of three proteinsbovine serum albumin (BSA), bovine immunoglobulin gamma (IgG) and fibrinogenonto five surface-modified organosilica microsphere surfaces was used as a model multicomponent system for analysis. By uniquely labeling each protein and solid support type with spectrally distinguishable fluorescent dyes, the adsorption process could be “multiplexed” allowing for simultaneous screening of multiple adsorbate (protein) and adsorbent (particle surface) interactions. Protein adsorption experiments quantified by flow cytometry were found to be comparable to single-component adsorption studies by solution depletion. Quantitative distribution of the simultaneous competitive adsorption of BSA and IgG indicated that, at concentrations below surface saturation, both proteins adsorbed onto the surface. However, at concentrations greater than surface saturation, BSA preferentially adsorbed. Multiplexed particle suspensions of optically encoded particles were modified to produce a positively and negatively charged surface, a grafted 3400 MW poly(ethylene glycol) layer, or a physisorbed BSA or IgG layer. It was observed that adsorption was rapid and irreversible on all of the surfaces, and preadsorbed protein layers were the most effective in preventing further protein adsorption. [ABSTRACT FROM AUTHOR]

The “informal” economy concerns activities directly bound to the most contemporary evolutions. Those related with the insertion of the ICTs in territories are demonstrations of a “paradoxical invention of the modernity” [JF Bayart 1994] with regard to the universalist classic model of the modernization spread by the West. Having explained briefly what we understand by “informal” according to various disciplinary approaches, we shall show how the insertion and the appropriation of the ICTs in the African cities gives place to a proliferation of new activities of service which are embedded in the urban fabric, adapt themselves to the low level of income of the populations and generate more or less qualified jobs which recover totally or partially from informal practices. We shall wonder finally about the proliferation of this “other economy” expression of the globalization.

We are, in 2006, at a crucial step of the Internet network development: the wide diffusion of the high bandwidth for new multi‑media uses which leads to rebuilding that one can characterize as a digital planning of territories. The problem is the same all around the world: to spread the high bandwidth at a correct cost for the various protagonists from the operator to the end‑user. The solutions to be implemented are the subject of discussions and struggles between various types of actors, private, public, associative, national and international, who are different according to their location at the center or in periphery of the system. Two economic logics are clashing: one which prevailed at the beginnings of the Internet, the co‑operative model where the network would become a world public property, and another which tends to spread today, the pure market logic. The case of Africa where the problems are exacerbated, illustrates what is at stake.

Our concrete analysis of the relationships between society and environment in coastal parts of Casamance, Guinea and Guinea Bissau associate two methods to represent a territory and its functioning that link space- and time- dimensions; SPOT's data and a model with "joined productions" or model of activities. The quantitative model created is nothing else than the systemic approach outcome in the material life field that is closely connected with operational research expressed in very general terms taking space in account. The analysis's heart is what links men, resources, technics in a changing territory. The term of "material production" does express this linkage, this interface. On the one hand, our researches are dealing with the processes by which humans make use of different forms of raw materials and goods available on their territory at the current of a given time, and on the other hand they are dealing with the result of these processes. So, we have defined a specific semantic and used a linear algebraic system, which materializes the connection rules of the processes, that is to say the phenomena of interconnected production and consumption, to build a formal and quantitative representation better adapted than natural language to a systemic and global description of societies' material reproduction. Such formalizations orientate the way of collecting data, especially in environments where statistics absence is generalized, they stimulate the functioning of a productive system, allow "to draw up the balance sheet" and to apprehend interactions, constraints, limiting factors existing at different levels of the material life functioning and allow to imagine the possible responses to cope with the changes (demographic growth, technical intensification, exodus). It is a contribution to the development "durability" on the lines as the models elaborated by Georgescu Roegen. That kind of quantitative method of analysis of a multifactual universe bound by changes can be in use to help with decisions; but it must be associated with other methods depending on anthropology to explain games and prospects from different actors beyond the material goods uses.