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Abstract Background Women who gain too much weight in pregnancy are at increased risk of disease and of having children with increased risk. Interventions to improve health behaviours are usually designed for a general population of pregnant women, and trial outcomes show an average impact that does not represent the differences between individuals. To inform the development of future interventions, this study explored the factors that influenced women’s diet and physical activity during pregnancy and aimed to identify the needs of these women with regards to lifestyle support. Methods Women who completed a trial of vitamin D supplementation and nurse support in pregnancy were invited to take part in an interview. Seventeen women were interviewed about their lifestyles during pregnancy, the support they had, and the support they wanted. Interview transcripts were coded thematically and analysed to understand the factors that influenced the diets and physical activity levels of these women and their engagement with resources that could provide support. Results Women identified barriers to eating well or being physically active, and pregnancy-specific issues like nausea and pain were common. Women’s interest in maintaining a healthy lifestyle and their engagement with lifestyle support was related to the extent to which they self-identified as healthy people. Health-disengaged women were disinterested in talking about their lifestyles while health-focused women did not feel that they needed extra support. Women between these ends of the ‘health identity’ spectrum were interested in improving their health, and were able to identify barriers as well as sources of support. Conclusions Lifestyle interventions in pregnancy should be adapted to meet the needs of individuals with different health identities, and encouraging a change in health identity may be one way of supporting sustained change in health behaviours.

IntroductionBrain hemorrhage was found between 13 and 16 days after acute whole-body 9.5 Gy 60Co-γ irradiation (IR). This study tested countermeasures mitigating brain hemorrhage and increasing survival from IR. Previously, we found that pegylated G-CSF therapy (PEG) (i.e., Neulasta®, an FDA-approved drug) improved survival post-IR by 20–40%. This study investigated whether Ciprofloxacin (CIP) could enhance PEG-induced survival and whether IR-induced brain hemorrhage could be mitigated by PEG alone or combined with CIP.MethodsB6D2F1 female mice were exposed to 60Co-γ-radiation. CIP was fed to mice for 21 days. PEG was injected on days 1, 8, and 15. 30-day survival and weight loss were studied in mice treated with vehicles, CIP, PEG, or PEG + CIP. For the early time point study, blood and sternums on days 2, 4, 9, and 15 and brains on day 15 post-IR were collected. Platelet numbers, brain hemorrhage, and histopathology were analyzed. The cerebellum/pons/medulla oblongata were detected with glial fibrillary acidic protein (GFAP), p53, p16, interleukin-18 (IL-18), ICAM1, Claudin 2, ZO-1, and complement protein 3 (C3).ResultsCIP + PEG enhanced survival after IR by 85% vs. the 30% improvement by PEG alone. IR depleted platelets, which was mitigated by PEG or CIP + PEG. Brain hemorrhage, both surface and intracranial, was observed, whereas the sham mice displayed no hemorrhage. CIP or CIP + PEG significantly mitigated brain hemorrhage. IR reduced GFAP levels that were recovered by CIP or CIP + PEG, but not by PEG alone. IR increased IL-18 levels on day 4 only, which was inhibited by CIP alone, PEG alone, or PEG + CIP. IR increased C3 on day 4 and day 15 and that coincided with the occurrence of brain hemorrhage on day 15. IR increased phosphorylated p53 and p53 levels, which was mitigated by CIP, PEG or PEG + CIP. P16, Claudin 2, and ZO-1 were not altered; ICAM1 was increased.DiscussionCIP + PEG enhanced survival post-IR more than PEG alone. The Concurrence of brain hemorrhage, C3 increases and p53 activation post-IR suggests their involvement in the IR-induced brain impairment. CIP + PEG effectively mitigated the brain lesions, suggesting effectiveness of CIP + PEG therapy for treating the IR-induced brain hemorrhage by recovering GFAP and platelets and reducing C3 and p53.

Insufficient invasion of conceptus-derived trophoblast cells in the maternal decidua is a key event in the development of early-onset preeclampsia (PE), a subtype of PE associated with high maternal and fetal morbidity and mortality. Kisspeptins, a family of peptides previously shown to inhibit trophoblast cell invasion, have been implicated in the pathogenesis of early-onset PE. However, a role of kisspeptin signaling during the genesis of this syndrome has not been elucidated. Herein, we used the preeclamptic-like BPH/5 mouse model to investigate kisspeptin expression and potential upstream regulatory mechanisms in a PE-like syndrome. Expression of the kisspeptin encoding gene, Kiss1, and the 10-amino-acid kisspeptide (Kp-10), are upregulated in the non-pregnant uterus of BPH/5 females during diestrus and in the maternal-fetal interface during embryonic implantation and decidualization. Correspondingly, the dysregulation of molecular pathways downstream to kisspeptins also occurs in this mouse model. BPH/5 females have abnormal sex steroid hormone profiles during early gestation. In this study, the normalization of circulating concentrations of 17β-estradiol (E2) and progesterone (P4) in pregnant BPH/5 females not only mitigated Kiss1 upregulation, but also rescued the expression of multiple molecules downstream to kisspeptin and ameliorated adverse fetoplacental outcomes. Those findings suggest that uterine Kiss1 upregulation occurs pre-pregnancy and persists during early gestation in a PE-like mouse model. Moreover, this study highlights the role of sex steroid hormones in uteroplacental Kiss1 dysregulation and the improvement of placentation by normalization of E2, P4 and Kiss1.

Abstract Empathy, the understanding of the emotional state of others, can be examined across species using the Perception Action Model, where shared affect promotes an action by “Observers” to aid a distressed “Target”. The anterior insula (AI) has garnered interest in empathic behavior due to its role integrating sensory and emotional information of self and other. In the following studies, the AI was inhibited pharmacologically and chemogenetically during targeted helping. We demonstrate the insula is active during, and is necessary for the maintenance of, targeted helping. Analysis of ultrasonic vocalizations revealed distress calls from Targets increased when Observers’ helping was attenuated due to insula inhibition. Targets’ elevated distress was directly correlated to Observers’ diminished helping behavior, suggesting emotional transfer between Observer and Target is blunted following Observer AI inhibition. Finally, the AI may selectively blunt targeted helping, as social exploration did not change in a social reward place conditioning task. These studies help further establish the anterior insula as a critical node in the empathic brain during targeted helping, even in the absence of direct social contact.

Here, the authors perform repurposing screens of the ReFRAME drug library in two cell lines and identify inhibitors of SARS-CoV-2 infection. Antiviral activity of prodrug MK-4482 is confirmed in hamsters.

Background: Coarctation of the aorta (CoA; constriction of the proximal descending thoracic aorta) is among the most common congenital cardiovascular defects. Coarctation-induced mechanical perturbations trigger a cycle of mechano-transduction events leading to irreversible precursors of hypertension including arterial thickening, stiffening, and vasoactive dysfunction in proximal conduit arteries. This study sought to identify kinetics of the stress-mediated compensatory response leading to these alterations using a preclinical rabbit model of CoA. Methods: A prior growth and remodeling (G&R) framework was reformulated and fit to empirical measurements from CoA rabbits classified into one control and nine CoA groups of various severities and durations (n = 63, 5–11/group). Empirical measurements included Doppler ultrasound imaging, uniaxial extension testing, catheter-based blood pressure, and wire myography, yielding the time evolution of arterial thickening, stiffening, and vasoactive dysfunction required to fit G&R constitutive parameters. Results: Excellent agreement was observed between model predictions and observed patterns of arterial thickening, stiffening, and dysfunction among all CoA groups. For example, predicted vascular impairment was not significantly different from empirical observations via wire myography (p-value > 0.13). Specifically, 48% and 45% impairment was observed in smooth muscle contraction and endothelial-dependent relaxation, respectively, which were accurately predicted using the G&R model. Conclusions: The resulting G&R model, for the first time, allows for prediction of hypertension precursors at neonatal ages that is currently challenging to examine in preclinical models. These findings provide a validated computational tool for prediction of persistent arterial dysfunction and identification of revised severity–duration thresholds that may ultimately avoid hypertension from CoA.

Childhood and adolescent obesity is a serious health problem that is on the rise at the global level. Earlier, certain diseases such as Type 2 diabetes, high blood pressure, and heart disease affected only adults, but now they are being detected in young children as well. Several studies based on machine learning have been proposed to develop obesity prediction models or to determine key determinants of obesity for designing intervention tools. Despite having a rich and diverse set of literature on obesity prediction models, obesity rates are at an all-time high for both children and adolescents. There is a need of proper understanding and critical analysis of existing machine learning models in order to design effective strategies for curbing obesity at childhood and adolescent level. This paper surveys the growing body of recent literature on machine and deep learning models for obesity prediction by providing a coherent view (critical analysis) of the limitations of the existing systems. The taxonomy of the existing literature on obesity prediction into methods used, predicted outcome, factors used, type of datasets, and the associated purpose, is discussed for analysis of the state-of-the-art. This analysis revealed that a) prediction-focused models do not use variables from as many domains as predictor-focused models do, b) very few studies proposed gender-specific and race-specific obesity prediction models, c) lack of large-scale multimodal datasets and d) existing predictor-focused models obtain an accuracy range of [53.7%, 96%] with an optimum set of predictors. Further, computer vision-based methods for obesity prediction and interpretable techniques for understanding the outcome of the models are discussed as well. In addition, we have also identified novel research directions. The overall aim is to advance the state-of-the-art and improve the quality of discourse in this field.

There is a growing appreciation for the idea that bacterial utilization of host-derived lipids, including cholesterol, supports Mycobacterium tuberculosis (Mtb) pathogenesis. This has generated interest in identifying novel antibiotics that can disrupt cholesterol utilization by Mtb in vivo. Here we identify a novel small molecule agonist (V-59) of the Mtb adenylyl cyclase Rv1625c, which stimulates 3', 5'-cyclic adenosine monophosphate (cAMP) synthesis and inhibits cholesterol utilization by Mtb. Similarly, using a complementary genetic approach that induces bacterial cAMP synthesis independent of Rv1625c, we demonstrate that inducing cAMP synthesis is sufficient to inhibit cholesterol utilization in Mtb. Although the physiological roles of individual adenylyl cyclase enzymes in Mtb are largely unknown, here we demonstrate that the transmembrane region of Rv1625c is required during cholesterol metabolism. Finally, the pharmacokinetic properties of Rv1625c agonists have been optimized, producing an orally-available Rv1625c agonist that impairs Mtb pathogenesis in infected mice. Collectively, this work demonstrates a role for Rv1625c and cAMP signaling in controlling cholesterol metabolism in Mtb and establishes that cAMP signaling can be pharmacologically manipulated for the development of new antibiotic strategies.

This study uses airborne data from two field campaigns off the California coast to characterize aerosol size distribution characteristics in the entrainment interface layer (EIL), a thin and turbulent layer above marine stratocumulus cloud tops, which separates the stratocumulus-topped boundary layer (STBL) from the free troposphere (FT). The vertical bounds of the EIL are defined in this work based on considerations of buoyancy and turbulence using thermodynamic and dynamic data. Aerosol number concentrations are examined from three different probes with varying particle diameter (Dp) ranges: > 3 nm, > 10 nm, and 0.11–3.4 µm. Relative to the EIL and FT layers, the sub-cloud (SUB) layer exhibited lower aerosol number concentrations and higher surface area concentrations. High particle number concentrations between 3 and 10 nm in the EIL are indicative of enhanced nucleation, assisted by high actinic fluxes, cool and moist air, and much lower surface area concentrations than the STBL. Slopes of number concentration versus altitude in the EIL were correlated with the particle number concentration difference between the SUB and lower FT layers. The EIL aerosol size distribution was influenced by varying degrees from STBL aerosol versus subsiding FT aerosol depending on the case examined. These results emphasize the important role of the EIL in influencing nucleation and aerosol–cloud–climate interactions.

As the need for environmental certification systems grows, Leadership in Energy and Environmental Design for New Construction (LEED-NC) is being widely adopted in the US to evaluate the environmental performance of buildings. However, no research has been conducted to investigate its economic impact on appraised land value. The objectives of this study are to quantify the impact of the LEED-NC Credit Alternative Transportation: Public Transportation Access (PTA) in the sustainable sites category on appraised land value and to develop a regression model that predicts the appraised unit value of parcels. San Francisco County was chosen because of its well-organized transportation systems. First, a LEED-NC map was created to identify PTA-qualified parcels. Second, sample parcels were randomly selected. Last, Pearson's correlation analysis, one-way ANOVA, and multiple linear regression analysis were sequentially performed. The results of this study indicated that the LEED PTA criteria are significant factors associated with an increase in the appraised unit value of parcels within San Francisco County. The findings of this study can encourage real-estate developers to site their projects according to the LEED-NC PTA criteria. [ABSTRACT FROM AUTHOR]

Abstract Multicatalytic proteinase complex (MCP) was studied in skeletal muscle of the hibernating ground squirrel, Spermophilus tridecemlineatus. MCP was partially purified using a S-400 gel filtration column and Centricon concentrating devices and assayed fluorometrically using three AMC-labeled substrates. Km and Vmax values were determined for each substrate with no significant differences between the enzyme from euthermic versus hibernating animals when assayed at 23 °C. However, properties of MCP from euthermic and hibernating ground squirrels were differentially affected by low assay temperature (8–10 °C) and also differed from the mouse enzyme, the data indicating that ground squirrel MCP is better suited for low temperature function. MCP preferentially degrades oxidatively-damaged proteins and quantification of protein carbonyl content showed that the level of oxidatively-damaged protein in skeletal muscle decreased by > 75% during hibernation suggesting a continuing role for the MCP in the torpid state. (Mol Cell Biochem 271: 205–213, 2005) [ABSTRACT FROM AUTHOR]

This is the last in a series of articles guiding nursing administrators from broad marketing strategy to tactics and specific applications. The first article laid the foundation for developing a market-driven strategic plan. The second focused on marketing from the inside out. This final article explores the benefits of specialty nurse certification as a strategy for nursing administrators to retain and recruit the most qualified nurses and to differentiate their services from those of competitors. The article includes findings from the American Association of Critical-Care Nurses’ proprietary research, suggestions on how to support certification, and a case study of one hospital’s experience in conducting a CCRN certification drive as part of their critical care nurse competency program. [ABSTRACT FROM AUTHOR]

The quinazolines CBR417 and CBR490 were previously shown to be potent anti-wolbachials that deplete Wolbachia endosymbionts of filarial nematodes and present promising pre-clinical candidates for human filarial diseases such as onchocerciasis. In the present study we tested both candidates in two models of chronic filarial infection, namely the Litomosoides sigmodontis and Brugia pahangi jird model and assessed their long-term effect on Wolbachia depletion, microfilariae counts and filarial embryogenesis 16−18 weeks after treatment initiation (wpt). Once per day (QD) oral treatment with CBR417 (50 mg/kg) for 4 days or twice per day (BID) with CBR490 (25 mg/kg) for 7 days during patent L. sigmodontis infection reduced the Wolbachia load by >99% and completely cleared peripheral microfilaremia from 10–14 wpt. Similarly, 7 days of QD treatments (40 mg/kg) with CBR417 or CBR490 cleared >99% of Wolbachia from B. pahangi and reduced peritoneal microfilariae counts by 93% in the case of CBR417 treatment. Transmission electron microscopy analysis indicated intensive damage to the B. pahangi ovaries following CBR417 treatment and in accordance filarial embryogenesis was inhibited in both models after CBR417 or CBR490 treatment. Suboptimal treatment regimens of CBR417 or CBR490 did not lead to a maintained reduction of the microfilariae and Wolbachia load. In conclusion, CBR417 or CBR490 are pre-clinical candidates for filarial diseases, which achieve long-term clearance of Wolbachia endosymbionts of filarial nematodes, inhibit filarial embryogenesis and clear microfilaremia with treatments as short as 7 days. Keywords: Quinazoline, Litomosoides sigmodontis, Brugia pahangi, Filaria, Doxycycline, Wolbachia, Macrofilaricidal, Microfilariae

People who inject drugs (PWID) are disproportionately affected by hepatitis C virus (HCV) infections and are frequently homeless. To improve HCV case finding in these individuals, we examined the feasibility of rapid HCV RNA testing in homeless services in Amsterdam. In 2020, we provided a comprehensive service to homeless facilities, which included workshops on HCV for personnel, a “hepatitis ambassador” at each facility, a rapid, onsite HCV RNA fingerstick test service, and assistance with linkage to care. Risk factors for HCV RNA-positive status were examined using Bayesian logistic regression. Of the 152 participants enrolled, 150 (87% men; median age: 47 years) accepted rapid HCV testing. Seven tested HCV RNA positive (4.7%, 95%CrI = 1.31–8.09; 7/150). Of these, five (71%) were linked to care, of whom four (57%, 4/7) initiated treatment and one (14%, 1/7) delayed treatment due to a drug–drug interaction. Of these four people, two completed treatment (50%), of whom one (25%) achieved sustained virologic response after 12 weeks. HCV RNA-positive individuals were more likely to originate from Eastern Europe (posterior-odds ratio (OR) = 3.59 (95% credible interval (CrI) = 1.27–10.04)) and to inject drugs (ever: posterior-OR = 3.89 (95% CrI = 1.37–11.09); recent: posterior-OR = 3.94 (95% CrI = 1.29–11.71)). We identified HCV RNA-positive individuals and linkage to care was relatively high. Screening in homeless services with rapid testing is feasible and could improve HCV case finding for PWID who do not regularly attend primary care or other harm reduction services for people who use drugs.

The increasing occurrence of natural disasters and their related damage have led to a growing demand for models that predict financial loss. Although considerable research on the financial losses related to natural disasters has found significant predictors, there has been a lack of comprehensive study that addresses the relationship among vulnerabilities, natural disasters, and the economic losses of individual buildings. This study identifies the vulnerability indicators for hurricanes to establish a metric to predict the related financial loss. We classify hurricane-prone areas by highlighting the spatial distribution of losses and vulnerabilities. This study used a Geographical Information System (GIS) to combine and produce spatial data and a multiple regression method to establish a wind damage prediction model. As the dependent variable, we used the value of the Texas Windstorm Insurance Association (TWIA) claim payout divided by the appraised values of the buildings to predict real economic loss. As independent variables, we selected a hurricane indicator and built environment vulnerability indicators. The model we developed can be used by government agencies and insurance companies to predict hurricane wind damage.

Aircraft–based measurements of cloud condensation nuclei (CCN), accumulation mode and Aitken mode number concentrations, cloud drop number concentration (CDNC), and selected ancillary measurements are presented for the three large, semi-permanent marine stratocumulus decks of the earth (in the Pacific offshore of California and Chile and in the Atlantic offshore of Namibia). Based on these data, a simple linear relationship between CDNC and the accumulation mode number concentration (AMNC) is derived via regression. The slope of the regression is 0.72 ± 0.04 with an R2 of 0.90, higher than those found for CDNC-CCN linear regressions. Explanations of the relatively favorable CDNC-AMNC relationship and its utility for climate studies are discussed.

Aircraft-based measurements of aerosol light-scattering coefficient, cloud condensation nuclei (CCN) measured directly or by proxy, and aerosol chemical composition are reported for three different years in the region of the large stratocumulus deck off the California coast. Receptor modeling is used to differentiate the contributions of the main aerosol sources to the light scattering and CCN activity. The contribution of anthropogenic sources to the two climatically important aerosol parameters (for direct and indirect forcing) varied from year to year but, on average, was found to be 67% in the case of CCN concentration and 57% in the case of light-scattering coefficient.

BACKGROUND:HIV patients on suppressive antiretroviral therapy have undetectable viremia making it impossible to screen plasma HIV tropism if regimen change is required during suppression. We investigated the prevalence and predictors of tropism switch from CCR5-using ("R5") to non-CCR5-using ("non-R5") before and after viral suppression in the initially therapy-naïve HOMER cohort from British Columbia, Canada. METHODS:We compared pre-therapy and post-suppression viral genotypic tropism in patients who initiated on PI/NNRTI-based antiretroviral regimens between 1996-1999 (n = 462). Virologic suppression was defined as having two consecutive viral loads of

This article reflects on the development of Computer Assisted Qualitative Data Analysis Software (CAQDAS) briefly before describing how the software can be harnessed to aid the process of research. It shows how data from a multi-user project looking at governance in UK Foundation Trust hospitals was enhanced and made clearer through the application of a specific method of gathering and coding data using a qualitative data analysis software package: Applying searches based on word frequency counts within NVivo 8 provided an initial categorisation of topics in an efficient manner allowing for a targeted examination of the overall data. This technique has been called by us the Mustard seed approach as it starts small and builds into something bigger over time. URL: http://nbn-resolving.de/urn:nbn:de:0114-fqs130231

This paper explores the analysis of complex multi-media data that highlights the latest advances in the kinds of data that can be analyzed using qualitative analytic software. The data examined consists of multiple simultaneous video streams with different video and audio content. The researchers found that multiple simultaneous transcripts can be useful in making sense of the very fast-moving content of these complex media files. The data capture and analysis techniques described provide the researcher with a tremendous level of access to a huge amount of simultaneous data, but the authors suggest that researchers in the analytic environment described are able to function well in the task of managing, understanding, and analyzing very complex data that captures very complex occurrences in the real world. URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs1101172

For the KWALON 2010 conference, several software representatives were given a common data set consisting of text and media files about the financial crisis of 2008 – 2009. This paper focuses on the process of analyzing the media files in this data set using Transana, a software package designed for the transcription and qualitative analysis of video and audio data. The authors describe several styles of transcription used in the process of making sense of the data, the selection and coding of analytically interesting segments of the media files, and working with coded data to develop a coherent narrative from this data. They also describe their collaborative process, as facilitated by the software, and how that affected the analysis of the data. Finally, the authors describe the results of their analysis in terms of the multi-layered narrative of the data, and discuss the limitations of that analysis. URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs1101169