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Summary Glucagon‐like‐peptide 1 receptor agonists (GLP‐1RA) have transformed type 2 diabetes (T2D) and obesity management. Multiple regulatory agencies are investigating reported associations between GLP1‐RA and increased suicide attempts (SA), but observational data may be prone to confounding. Randomised control trials (RCT) of GLP‐1RA were largely undertaken in people at lower risk of SA. Real‐world data suggest semaglutide use associates with reduced suicidal ideation and depression but was under‐powered to statistically assess risk of SA. Mendelian randomisation (MR) leverages genetic instrument(s) to infer potential causal association between an exposure and an outcome. We undertook MR using missense variants in the gene encoding GLP1R that improve glycemia, lower T2D risk and/or lower BMI, to investigate potential causal association between GLP‐1RA and SA. In people of European ancestry, MR did not find evidence genetically proxied GLP1RA increased SA in a general population cohort: (rs10305492, exposure: HbA1c, odds ratio [OR] and 95% confidence interval [CI]: 1.38, 0.41–4.62, p = .60), (rs10305492, exposure: FG, OR 1.27, 0.52–3.13, p = .60) and (rs1042044, exposure BMI, OR 0.30, 0.06–1.48) with concordant results in a multi‐ancestry SA case–control cohort. In conclusion, we did not find MR evidence that increased GLP‐1RA impacts SA. This awaits confirmation with RCT and real‐world data. [ABSTRACT FROM AUTHOR]

Tissue fibrosis following tendon injury is a major clinical problem due to the increased risk of re-injury and limited treatment options; however, its mechanism remains unclear. Evidence suggests that insufficient resolution of inflammation contributes to fibrotic healing by disrupting tenocyte activity, with the NF-κB pathway being identified as a potential mediator. Equine embryonic stem cell (ESC) derived tenocytes may offer a potential cell-based therapy to improve tendon regeneration, but how they respond to an inflammatory environment is largely unknown. Our findings reveal for the first time that, unlike adult tenocytes, ESC-tenocytes are unaffected by IFN-γ, TNFα, and IL-1β stimulation; producing minimal changes to tendon-associated gene expression and generating 3-D collagen gel constructs indistinguishable from unstimulated controls. Inflammatory pathway analysis found these inflammatory cytokines failed to activate NF-κB in the ESC-tenocytes. However, NF-κB could be activated to induce changes in gene expression following stimulation with NF-κB pharmaceutical activators. Transcriptomic analysis revealed differences between cytokine and NF-κB signalling components between adult and ESC-tenocytes, which may contribute to the mechanism by which ESC-tenocytes escape inflammatory stimuli. Further investigation of these molecular mechanisms will help guide novel therapies to reduce fibrosis and encourage superior tendon healing. [ABSTRACT FROM AUTHOR]

Word formation in most languages is inextricably linked to a distinction between clitics and affixes. Although famous for its templatic morphological structure, Arabic also contains concatenative formatives some of whose status as clitics or affixes is controversial. It is well known that Arabic varieties exhibit a range of interacting shortening and lengthening processes. Some of the shortening processes have been linked to the clitic/affix distinction in the Arabic literature. In this paper, I discuss two vowel shortening processes, CSS‐Morph and CSS‐Phon, that are often conflated as the same Closed Syllable Shortening process. Based on evidence from 16 modern Arabic varieties, I show that these CSS processes are in fact two independent processes. While CSS‐Morph is a phonological alternation within a morphophonological context, CSS‐Phon is purely phonological. Neither provides evidence to classify any formative as a clitic or indeed differentiate between formatives as suffixes or clitics. [ABSTRACT FROM AUTHOR]

A series of experiments was designed to evaluate treatment schedules for control of the estrous cycle in which luteolysis is induced prior to atresia of the first follicular wave following a long-term progestin presynchronization treatment in beef heifers. The overarching hypothesis was that the proportion of heifers undergoing luteolysis and expressing estrus following PG administration would be affected by the duration of treatment with an intravaginal progesterone-releasing insert (CIDR; 1.38 g progesterone) and/or by the interval from CIDR removal to prostaglandin F 2ɑ (PG; 500 μg cloprostenol) administration. In each experiment, heifers were blocked by reproductive tract score (RTS) and body weight (BW) and were assigned randomly within block to treatment. In Experiment 1, heifers (n = 91) were assigned to one of four treatments in a 2 x 2 factorial design: presynchronization via CIDR treatment for either 14 d or 18 d with administration of PG either 8 d or 9 d following CIDR removal. In Experiment 2, heifers (n = 63) were assigned to receive administration of PG either 9 d or 10 d following a 14 d CIDR presynchronization. In Experiment 3, heifers (n = 83) were assigned to receive administration of PG either 9 d or 16 d following a 14 d CIDR presynchronization. In Experiment 1, there was a tendency for a greater proportion of heifers to express estrus by 96 h after PG administration when PG administration occurred 9 d versus 8 d after CIDR removal (P = 0.07). Additionally, serum estradiol (E 2) concentrations were greater at the time of PG administration when PG was administered 9 d versus 8 d after CIDR removal following an 18 d CIDR treatment (P = 0.006). In Experiment 2, pregnancy rate to AI (P/AI) was greater among heifers receiving PG administration 9 d versus 10 d after CIDR removal (P = 0.03). There was a tendency for largest follicle diameter (LFD) to be greater among non-estrous heifers receiving PG administration 10 d versus 9 d after CIDR removal when measured at timed AI (P < 0.08). In Experiment 3, there was a tendency for serum progesterone (P 4) concentrations at the time of PG administration to be greater among heifers receiving PG administration 16 d versus 9 d after CIDR removal (P = 0.07). These results provide a preliminary evaluation of the feasibility of inducing luteolysis prior to atresia of the first follicular wave following long-term progestin presynchronization. [Display omitted] • Shorter intervals to PG administration following progestin presynchronization were evaluated. • Inducing luteolysis prior to atresia of the first follicular wave may be feasible. • Shorter interval to PG could reduce pregnancy rates if some CL are not responsive. [ABSTRACT FROM AUTHOR]

Social workers have emerged as leaders within Addiction Consult Services (ACS) due to their ability to provide a wide range of services, from crisis work and brief therapeutic interventions to connecting patients to community resources. Many hospitals have implemented ACS to address the overdose crisis and the sharp rise in drug use-related infections, including skin and soft tissue infections, osteomyelitis, and endocarditis; a result of unaddressed systemic social determinants of health (SDOH). Yet, despite social workers being at the forefront of inpatient substance use work, little guidance exists regarding social work's role in leading person-centered addiction care and addressing SDOH in the hospital setting. The authors of this paper are licensed clinical social workers who have worked across five different health systems, engaging persons who use drugs (PWUD) in the context of an ACS. This paper examines five practice interventions of social work practice within hospitals that represent key points for innovation. Drawing on social work's unique commitments to social justice, strengths, and person-in-environment, these interventions operate within eco-social approaches to help us grapple more effectively with ways that health – and disease – are socially and economically produced by multiple interacting factors. We provide a clinical roadmap of interventions for social workers in hospital settings with PWUD to demonstrate how social work leadership within inpatient care models can help us better address the impacts of various intersecting SDOH on the care of PWUD. [ABSTRACT FROM AUTHOR]

The specific relationship between sexual coercion, intimate partner violence (IPV) during pregnancy, and intimate partner homicide (IPH) is poorly understood. Through a scoping literature review, we identified 101 studies on sexual coercion, IPV during pregnancy, and IPH and created a conceptual model suggesting unintended pregnancies may serve as both a risk factor for and a product of IPV that may escalate to IPH. We illustrate a healthcare systems intervention implication of this model in the context of the Colorado Family Planning Initiative (CFPI). Descriptive statistics suggest an inverse association between contraception access and IPH, which declined by 62% during the first 4 years of the CFPI. Interventions aimed at improving reproductive agency, including improving contraception access and reducing unintended pregnancy, may be a useful opportunity for clinician and health systems to contribute to reducing both lethal and nonlethal IPV. [ABSTRACT FROM AUTHOR]

Interest in the use of carbonate precipitation for the purposes of soil stabilization, carbon capture and environmental remediation has created a need for geophysical techniques capable of characterizing the 3-D extent of precipitation in the subsurface. The use of spectral induced polarization, a geophysical technique sensitive to mineral precipitation and dissolution processes, has been investigated in previous studies; nevertheless, debate still exists regarding measured induced polarization (IP) signals relating to the formation of calcite. In this study, calcite was precipitated within gel-saturated media through highly controlled double-diffusion methods. Three experiments were conducted to study both the inherent IP response of calcite in isolation, as well as the IP response when precipitated within a low-polarizability background medium (quartz sand) and a high-polarizability medium (a sand–magnetite mixture). The results support that in isolation, the polarization of the electrical double layer surrounding individual calcite grains is not a significant contributor to IP signatures from calcite precipitation. However, under certain circumstances the precipitation of calcite, in the quartz-sand and sand–magnetite mixtures, can produce a strong IP response when the precipitation blocks a current conduction pathway. If metallic mineral grains are present then they may act as conduits for current if they become embedded in an insulating calcite wall, creating a significant electrode polarization which dominates the IP signal. Equivalent circuit models indicate that the precipitation of calcite as a thin planar front normal to the current path is analogous to a simple lossy capacitor blocking most DC current but being thin enough to measurably polarize. Circuit models also suggest that the total impedance seen from the sand–magnetite sample is simply the sum of the impedance of the disseminated grains and the grains encased in the calcite front. The encased grains also have a higher relaxation time which may indicate a different polarization mechanism than from disseminated magnetite. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to establish the demographic profile of adult patients presenting with constipation and constipation‐related issues to an Australian tertiary hospital ED, investigate ED management and referral pathways in this cohort and determine satisfaction of these aspects of care from a patient's perspective. Methods: This is a single‐centre study conducted in an Australian tertiary hospital ED which sees 115 000 presentations annually. ED presentations of adults aged 18–80 years with symptoms of constipation were evaluated through retrospective electronic medical record audit and follow‐up by survey 3–6 months after their ED presentation. Results: The patients presenting to the ED with constipation had a median age of 48 years (IQR 33.5–63.5) and arrived self‐referred by private transport. Median length of stay was 292 min. 22% of patients reported they had previously attended the ED for the same issue within the previous year. Diagnosis of chronic constipation was inconsistent, with limited supporting documentation. Constipation was largely managed with aperients. Four in five patients were satisfied with ED care; however, 3–6 months post‐ED visit, 92% of patients reported ongoing bowel‐related issues, reflecting the chronic course of functional constipation. Conclusion: This is the first study to investigate the management of constipation in adult patients in an Australian ED setting. It is important that ED clinicians recognise that functional constipation is a chronic condition and many patients have persistent symptoms. There are opportunities for quality‐of‐care improvements including diagnostics, treatment, and referral post‐discharge to allied health, nursing and medical specialist services. [ABSTRACT FROM AUTHOR]

The increasing prevalence of antibiotic-resistant bacteria poses a significant threat to global human health. Countering this threat requires the public to understand the causes of, and risks posed by, antibiotic resistance (AR) to support changing healthcare and societal approaches to antibiotic use. To gauge public knowledge, we designed a questionnaire to assess awareness of causes of AR (both personal and societal) and knowledge of absolute and relative risks posed by antibiotic-resistant bacteria. Our findings reveal that while >90% respondents recognized personal behaviours as limiting AR, few individuals recognized the importance of societal factors e.g. the use of antibiotics in livestock. Furthermore, more respondents named viruses (either by name or as a group) than bacteria as reasons to take antibiotics, indicating lack of understanding. The absolute numbers of current and predicted future deaths attributed to antibiotic-resistant bacteria were under-estimated and respondents were more concerned about climate change and cancer than AR across all age groups and educational backgrounds. Our data reveal that despite heightened public awareness of infection-control measures following the COVID-19 pandemic, there remains a knowledge gap related to contributors and impacts of increasing numbers of antibiotic-resistant bacteria. [ABSTRACT FROM AUTHOR]

The current set of experiments was designed to explore the processing of spatial information during reading, specifically the spatial-shift effect and the spatial-gradient effect. Experiments 1 and 2 demonstrated that when participants were presented with text alone (i.e., without prior map memorization, virtual environments, task demands, or prior knowledge of the spatial information), the spatial-shift effect does emerge. Using the time to name a spatial location as a measure of spatial activation, participant naming times were faster for the original spatial location when the protagonist had moved a smaller distance relative to when the protagonist had moved a larger distance. Further, Experiment 3 provided evidence to support that a spatial gradient of activation is evident; this was done by adding an additional point of spatial distance in which the protagonist did not move from the initial location. The results are discussed within the context of the memory-based view of text comprehension. [ABSTRACT FROM AUTHOR]

Background: Brief motivational interventions (BMIs) are one of the most effective individually focused alcohol intervention strategies for college students. Despite the central theoretical role of motivation for change in BMIs, it is unclear whether BMIs increase motivation to change drinking behavior. We conducted a two‐step meta‐analysis of individual participant data (IPD) to examine whether BMIs increase motivation for change. N = 5903;59% women, 72% White) from Project INTEGRATE. The BMIs included individually delivered motivational interviewing with personalized feedback (MI + PF), stand‐alone personalized feedback (PF), and group‐based motivational interviewing (GMI). Methods: We included 15 trials of BMI (N = 5903;59% women, 72% White) from Project INTEGRATE. The BMIs included individually‐delivered motivational interviewing with personalized feedback (MI + PF), stand‐alone personalized feedback (PF), and group‐based motivational interviewing (GMI). Different measures and responses used in the original trials were harmonized. Effect size estimates were derived from a model that adjusted for baseline motivation and demographic variables for each trial (step 1) and subsequently combined in a random‐effects meta‐analysis (step 2). Results: The overall intervention effect of BMIs on motivation for change was not statistically significant (standard mean difference [SMD]: 0.026, 95% CI: [−0.001, 0.053], p = 0.06, k = 19 comparisons). Of the three subtypes of BMIs, GMI, which tended to provide motivation‐targeted content, had a statistically significant intervention effect on motivation, compared with controls (SMD: 0.055, 95% CI: [0.007, 0.103], p = 0.025, k = 5). By contrast, there was no evidence that MI + PF (SMD = 0.04, 95% CI: [−0.02, 0.10], k = 6, p = 0.20) nor PF increased motivation (SMD = 0.005, 95% CI: [−0.028, 0.039], k = 8, p = 0.75), compared with controls. Post hoc meta‐regression analysis suggested that motivation sharply decreased each month within the first 3 months postintervention (b = −0.050, z = −2.80, p = 0.005 for k = 14). Conclusions: Although BMIs provide motivational content and normative feedback and are assumed to motivate behavior change, the results do not wholly support the hypothesis that BMIs improve motivation for change. Changing motivation is difficult to assess during and following interventions, but it is still a theoretically important clinical endpoint. Further, the evidence cautiously suggests that changing motivation may be achievable, especially if motivation‐targeted content components are provided. [ABSTRACT FROM AUTHOR]

Historically, gaining peripheral intravenous (IV) access for patients with difficult intravenous access (DIVA) has been problematic and associated with increased complications, central venous access device insertion and reduced patient satisfaction. Consequently, extended-length peripheral intravenous catheters (PIVCs) have been developed, but to date no real-world data exploring their effectiveness with NHS patients has been published. This article reports on the results of introducing extended-length PIVCs, inserted using ultrasound guidance in patients with DIVA by a vascular access team. This began in 2019, across an adult tertiary hospital setting in the NHS with about 750 beds. The specialties at this hospital include, but are not limited to, emergency medicine; head and neck; vascular; diabetes and endocrinology; respiratory; care of the older person; stroke services; gastroenterology; and trauma and orthopaedics. The vascular access team recorded 1485 individual insertions between 2019 to 2022, with a mean dwell time of 6 days, a first attempt success rate of 91%, and a therapy completion rate of 75 and 78% for inpatient and outpatients respectively. Indications included administration of IV fluids, medication, blood products and access for investigations or procedures. Obtaining reliable IV access in patients with DIVA prevents treatment delays, cancelled or delayed procedures, both of which benefit patients and the healthcare organisation. The data presented in this study support the use of extended-length PIVCs in patients with DIVA and has led to the development of new referral pathways. [ABSTRACT FROM AUTHOR]

Introduction A unilateral or bilateral pars interarticularis defect (spondylolysis) is a leading cause of axial back pain in adolescent athletes. Currently, a spectrum of imaging modalities is used for assessment of pars interarticularis defects. Objectives The aim of this study is to compare the accuracy of chemical shift sequence (magnetic resonance imaging [MRI]) technique to conventional MRI sequences in the detection of pars defects. Patients and Methods Conventional T1, T2, and short tau inversion recovery sagittal and axial, as well as "in-" and "out-" phase chemical shift sagittal MRI sequences of 70 consecutive patients referred for low back pain were reviewed. Demographic details, clinical indication, and presence/diagnosis of pars defects using a 5-point Likert scale on both conventional and chemical shift MRI sequences. Spearman's correlation was used for statistical analysis. Intraclass correlation coefficient analysis was evaluated to assess the intraclass reliability between observers. Data were analyzed using DATAtab web-based statistics software (2022). Results A total of 70 patients with an average age of 54.34 years with a female predominance were included. There were 11 pars defects in the cohort. Both in and out phases of chemical shift imaging were able to identify pars defect and intact pars. However, out phase was relatively better in delineating pars defects, while the in phase was superior in identifying an intact pars, though this was not statistically significant. There was good intra- and interobserver reliabilities. Conclusion Chemical shift MRI sequence is a quicker, complementary technique to assess and analyze pars interarticularis confidently than conventionally utilized MRI sequences in patients being evaluated for axial back pain. [ABSTRACT FROM AUTHOR]

There is growing evidence that the provision of nutritious supplemental foods to undernourished pregnant women can improve maternal and infant outcomes. However, comparing and synthesizing the evidence base is complicated by differences in interventions and products and the use of ambiguous terminology. We aimed to define 2 common types of nutritious supplemental foods used in pregnancy, balanced energy-protein (BEP) supplements and lipid-based nutrient supplements (LNS), and to review the evidence supporting each via a narrative review of systematic reviews and meta-analyses (SRMAs). Information about the nutritional composition of the food supplements and their effects on maternal and infant outcomes was abstracted. Five SRMAs (n = 20 trials) evaluated the effect of BEP compared with no BEP/control (comparison group commonly received iron and folic acid [IFA]). BEP foods/products ranged in calories (118-1017 kcals), protein (3-50 g), fat (6-57 g), and micronutrient content. Overall, maternal BEP improved birth weight and reduced the risk of stillbirth and small for gestational age when compared with no BEP/control in pregnancy. Three SRMAs (n = 5 trials) evaluated the effect of LNS compared with IFA or multiple micronutrients (MMNs). The LNS interventions comprised small- and large-quantity LNS that ranged in calories (118-746 kcals), protein (3-21 g), fat (10-53 g), and micronutrient content. LNS compared with IFA increased pregnancy duration, birth weight, and birth length and reduced the risk of small for gestational age and infant stunting; however, no beneficial effect of LNS was identified when compared with MMN. Despite heterogeneity in the nutritional composition of BEP supplements, the evidence suggests that in nutritionally at-risk populations, these products may improve birth outcomes in pregnant women. The evidence is limited but promising when LNS is compared with IFA in improving maternal and infant outcomes. Overall, BEP, compared with MMN or LNS, are key areas that have not been studied and deserve attention. [ABSTRACT FROM AUTHOR]

Background. Cervical pregnancy, an uncommon type of ectopic pregnancy, can lead to devastating consequences if not diagnosed and treated early. Despite this, there are no specific guidelines on how to treat such pregnancies especially in advanced gestational ages (GAs). Case. This is a 35-year-old patient who presented to our hospital at 13 weeks GA after failing systemic multidose methotrexate therapy for a cervical ectopic pregnancy. Given desire to preserve fertility, a minimally invasive conservative approach was taken involving potassium chloride (KCl) and methotrexate injections into the gestational sac, followed by immediate Cook intracervical double balloon placement under direct ultrasound visualization, with removal of the balloon after 72 hours, and ultimately resolution of the pregnancy 12 weeks after the removal. Conclusion. Advanced first trimester cervical ectopic pregnancy after failure of methotrexate therapy was managed successfully with minimally invasive KCl and methotrexate injections in combination with cervical ripening balloon. [ABSTRACT FROM AUTHOR]

We sought to determine the feasibility of identifying and quantifying mesenchymal stem cells (MSCs) from umbilical cord blood (UCB) after delayed cord clamping in preterm and term births. We obtained 3 mL of UCB at various gestational ages after delayed cord clamping. UCB separated by density gradient centrifugation within 4 h of delivery was passed through magnetic bead micro-columns to exclude the CD34 + cell population. The samples were incubated with fluorescent-tagged mesenchymal cell marker antibodies CD 29, CD44, CD73, CD105, and hematopoietic cell marker CD45. The cell populations were analyzed by flow cytometry. Viable cells were assessed with 7-aminoactinomycin-D. The results were expressed in median (minimum to maximum) MSCs and compared between preterm and term samples. A total of 12 UCB samples (32–40 weeks) were obtained, 10 of which demonstrated MSCs, accounting for 0.0174% (0–14.7%) of the viable UCB mononuclear cells. MSCs comprised 0.148% (0.0006–1.59%) and 0.116% (0–14.7%) of the viable UCB mononuclear cells in the term (n = 5), 38.4 ± 1.3 weeks, and preterm (n = 7) samples, 34.6 ± 1.1, respectively, p = 0.17. There was an overall median of 96 (0–39,574) MSCs. There was no difference in the median numbers of MSCs identified between term and preterm UCB samples, 3384 (23–6042) and 36 (0–39,574), respectively, p = 0.12. Mesenchymal stem cells were identified and quantified in 5 of 7 preterm and all 5 term UCB 3-mL samples obtained after delayed cord clamping. [ABSTRACT FROM AUTHOR]

The Ediacaran--Cambrian boundary strata in the Great Basin of the southwestern United States record biological, geochemical, and tectonic change during the transformative interval of Earth history in which metazoans diversified. Here, we integrate new and compiled chemostratigraphic, paleontological, sedimentological, and stratigraphic data sets from the Death Valley region, the White-Inyo Ranges, and Esmeralda County in Nevada and California and evaluate these data within a regional geologic framework. A large negative carbon isotope (δ13C) excursion--also known as the Basal Cambrian Excursion, or BACE--is regionally reproducible, despite lateral changes in sedimentary facies and dolomitization across ~250 km, consistent with a primary marine origin for this perturbation. Across the southern Great Basin, Ediacaran body fossils are preserved in a variety of taphonomic modes, including cast and mold preservation, two-dimensional compressional preservation, two-dimensional and three-dimensional pyritization, and calcification. The stratigraphic framework of these occurrences is used to consider the relationships among taphonomic modes for fossil preservation and paleoenvironmental settings within this basin. In this region, Ediacaran-type fossils occur below the nadir of the BACE, while Cambrian-type trace fossils occur above. Sedimentological features that include giant ooids, stromatolites, and textured organic surfaces are widespread and abundant within the interval that records biotic turnover and coincide with basaltic volcanism and the BACE. We hypothesize that the prevalence of these sedimentological features, the BACE, and the disappearance of some Ediacaran clades were caused by environmental perturbation at the Ediacaran--Cambrian boundary. [ABSTRACT FROM AUTHOR]

Recreational fishing with the principal motivation of leisure is associated with important economic, social and conservation values. Nonetheless, it is also a primary pathway for the introduction and spread of invasive non‐native species and aquatic animal disease. Several studies have explored the overall biosecurity risk posed by recreational anglers based on self‐reported behaviours and the awareness of biosecurity campaigns. Nonetheless, there has been little in‐depth exploration of the characteristics of key stakeholders who are implementing biosecurity best practices and the barriers that prevent anglers from undertaking biosecurity measures in the field. This study addresses this knowledge gap using an online questionnaire to collect information on angler socio‐demographic characteristics, voluntary biosecurity behaviour and barriers affecting the implementation of biosecurity best practices in Great Britain. The results indicated that cleaning behaviours vary considerably among anglers, with angling frequency and the number of pieces of equipment affecting how likely anglers were to clean and dry these items. High levels of disinfectant use were reported among anglers, potentially attributed to the concurrent advocation of disinfectant to prevent the spread of aquatic animal disease. Barriers affecting the implementation of correct cleaning behaviours included a combination of factors, such as practicality, disability, lack of available information and individual values. These findings illustrate the importance for fishery managers, water companies and policymakers to tailor prevention measures and facilities for anglers to maximise the practicality of biosecurity measures and encourage long‐term implementation of best practices. [ABSTRACT FROM AUTHOR]

Tendon injuries occur commonly in both human and equine athletes, and poor tendon regeneration leads to functionally deficient scar tissue and an increased frequency of re-injury. Despite evidence suggesting inadequate resolution of inflammation leads to fibrotic healing, our understanding of the inflammatory pathways implicated in tendinopathy remains poorly understood, meaning successful targeted treatments are lacking. Here, we demonstrate IL-1β, TNFα and IFN-γ work synergistically to induce greater detrimental consequences for equine tenocytes than when used individually. This includes altering tendon associated and matrix metalloproteinase gene expression and impairing the cells' ability to contract a 3-D collagen gel, a culture technique which more closely resembles the in vivo environment. Moreover, these adverse effects cannot be rescued by direct suppression of IL-1β using IL-1RA or factors produced by BM-MSCs. Furthermore, we provide evidence that NF-κB, but not JNK, P38 MAPK or STAT 1, is translocated to the nucleus and able to bind to DNA in tenocytes following TNFα and IL-1β stimulation, suggesting this signalling cascade may be responsible for the adverse downstream consequences of these inflammatory cytokines. We suggest a superior approach for treatment of tendinopathy may therefore be to target specific signalling pathways such as NF-κB. [ABSTRACT FROM AUTHOR]

Since the 1980s, the existence of one or more extinction events in the late Ediacaran has been the subject of debate. Discussion surrounding these events has intensified in the last decade, in concert with efforts to understand drivers of global change over the Ediacaran-Cambrian transition and the appearance of the more modern-looking Phanerozoic biosphere. In this paper we review the history of thought and work surrounding late Ediacaran extinctions, with a particular focus on the last 5 years of paleontological, geochemical, and geochronological research. We consider the extent to which key questions have been answered, and pose new questions which will help to characterize drivers of environmental and biotic change. A key challenge for future work will be the calculation of extinction intensities that account for limited sampling, the duration of Ediacaran 'assemblage' zones, and the preponderance of taxa restricted to a single 'assemblage'; without these data, the extent to which Ediacaran bioevents represent genuine mass extinctions comparable to the 'Big 5' extinctions of the Phanerozoic remains to be rigorously tested. Lastly, we propose a revised model for drivers of late Ediacaran extinction pulses that builds off recent data and growing consensus within the field. This model is speculative, but does frame testable hypotheses that can be targeted in the next decade of work. [ABSTRACT FROM AUTHOR]

Management of cerebral venous thrombosis (CVT) involves minimizing expansion of the thrombus and promoting the recanalization of the venous sinus. While current guidelines include indications of endovascular management and anticoagulation with heparin and warfarin, the use of direct-acting oral anticoagulants (DOACs) has increased. In this study, we aim to conduct a network meta-analysis comparing these 3 therapeutic options: standard anticoagulation, DOACs, and endovascular treatments (EVTs). Seventeen of 2265 studies identified from 4 publication databases met inclusion criteria for this network meta-analysis. Outcomes analyzed included modified Rankin Scale score, complications, mortality, and 6-month recanalization rates using a frequentist network meta-analysis approach. For each outcome, the preferential order of each intervention was ranked hierarchically based on P-score calculations used for frequentist network meta-analyses. Modified Rankin Scale outcomes were not significantly different based on the type of treatment modality (i.e., standard anticoagulation, DOACs, or EVT). Evaluation of complications demonstrated that patients treated with EVT were significantly more likely to experience a worse outcome than individuals treated with standard anticoagulation (odds ratio [OR] = 1.83, P = 0.04). Other comparisons did not demonstrate a significant difference in adverse events. For all-cause mortality outcomes, EVT demonstrated significantly greater odds of mortality than standard anticoagulation (OR = 1.89, P = 0.02). Mortality between DOACs and standard anticoagulation was not significantly different. When comparing 6-month recanalization rates, DOACs and EVT were significantly more effective than standard anticoagulation (OR = 1.93, OR = 2.2, P < 0.05). EVT followed by DOACs was preferred over standard anticoagulation for 6-month recanalization rates. This network meta-analysis evaluates the outcomes in CVT treatment, comparing standard anticoagulation, DOACs, and EVT, with evidence that DOACs have similar outcomes to standard anticoagulation in the treatment of CVT. EVT resulted in an increased risk of overall mortality but improved 6-month recanalization rates. [Display omitted] [ABSTRACT FROM AUTHOR]

A case study of 15-year-old female is presented with right facial swelling. Topics include examines she developed swelling of her right upper lip after rupturing a pimple on her top lip and she had no previous skin infection, sinusitis, or other facial trauma and focuses on erythema developing and the swelling progressed to include her right eye, cheek, both lips, and around her jaw line.

Objectives: To reduce preventable deaths of newborns and children, the United Nations set a target rate per 1000 live births of 12 for neonatal mortality (NMR) and 25 for under-5 mortality (U5MR). The purpose of this paper is to define the minimum surgical workforce needed to meet these targets and evaluate the relative impact of increasing surgeon, anesthesia, and obstetrician (SAO) density on reducing child mortality. Methods: We conducted a cross-sectional study of 192 countries to define the association between surgical workforce density and U5MR as well as NMR using unadjusted and adjusted B-spline regression, adjusting for common non-surgical causes of childhood mortality. We used these models to estimate the minimum surgical workforce to meet the sustainable development goals (SDGs) for U5MR and NMR and marginal effects plots to determine over which range of SAO densities the largest impact is seen as countries scale-up SAO workforce. Results: We found that increased SAO density is associated with decreased U5MR and NMR (P < 0.05), adjusting for common non-surgical causes of child mortality. A minimum SAO density of 10 providers per 100,000 population (95% CI: 7–13) is associated with an U5MR of < 25 per 1000 live births. A minimum SAO density of 12 (95% CI: 9–20) is associated with an NMR of < 12 per 1000 live births. The maximum decrease in U5MR, on the basis of our adjusted B-spline model, occurs from 0 to 20 SAO per 100,000 population. The maximum decrease in NMR based on our adjusted B-spline model occurs up from 0 to 18 SAO, with additional decrease seen up to 80 SAO. Conclusions: Scale-up of the surgical workforce to 12 SAO per 100,000 population may help health systems meet the SDG goals for childhood mortality rates. Increases in up to 80 SAO/100,000 continue to offer mortality benefit for neonates and would help to achieve the SDGs for neonatal mortality reduction. [ABSTRACT FROM AUTHOR]

Objective: Individuals with intellectual and/or developmental disability (IDD) are often prescribed antipsychotics (APs). However, despite their known propensity to cause metabolic adverse effects, including weight gain, diabetes, and increased risk of cardiovascular events, there is currently a limited body of literature describing the metabolic consequences of AP use in this population. Methods: We searched MEDLINE, EMBASE, PsychINFO, CENTRAL, and CINAHL databases to identify all randomized trials that reported on the metabolic effects of APs in individuals with IDD. Random effects meta‐analyses were used to examine weight gain as both a continuous and dichotomous outcome. Results: Eighteen randomized trials met our inclusion criteria with a total of 1376 patients across a variety of IDDs. AP use was associated with significantly greater weight gain compared with placebo (Continuous: mean difference = 1.10 kg, [0.79, 1.40], p < 0.00001, I2 = 54%; Dichotomous: odds ratio = 3.94, [2.15, 7.23], p < 0.00001, I2 = 0). Sub‐group analysis revealed no significant effect of AP type. Data regarding the effects of APs on other metabolic outcomes were limited. Conclusion: This review (PROSPERO # CRD42021255558) demonstrates that AP use is associated with significant weight gain among patients with IDD. Concerningly, most reported studies were in children and adolescents, which sets up an already vulnerable population for adverse medical sequalae at an early age. There was also a lack of long‐term studies in adults with IDD. Further studies are required to better understand how AP use affects metabolic parameters in this group of individuals. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Responsive feeding may improve health outcomes in preterm and low birth weight (LBW) infants. Our objective was to assess effects of responsive compared with scheduled feeding in preterm and LBW infants. METHODS: Data sources include PubMed, Scopus, Web of Science, CINAHL, LILACS, and MEDICUS. Randomized trials were screened. Primary outcomes were mortality, morbidity, growth, neurodevelopment. Secondary outcomes were feed intolerance and duration of hospitalization. Data were extracted and pooled with random-effects models. RESULTS: Eleven eligible studies were identified, and data from 8 randomized control trials with 455 participants were pooled in the meta-analyses. At discharge, the mean difference in body weight between the intervention (responsive feeding) and comparison (scheduled feeding) was - 2.80 g per day (95% CI -3.39 to -2.22, I² = 0%, low certainty evidence, 4 trials, 213 participants); -0.99 g/kg per day (95% CI -2.45 to 0.46, I² = 74%, very low certainty evidence, 5 trials, 372 participants); -22.21 g (95% CI -130.63 to 86.21, I² = 41%, low certainty evidence, 3 trials, 183 participants). The mean difference in duration of hospitalization was -1.42 days (95% CI -5.43 to 2.59, I² = 88%, very low certainty evidence, 5 trials, 342 participants). There were no trials assessing other growth outcomes (eg, length and head circumference) mortality, morbidity or neurodevelopment. Limitations include a high risk of bias, heterogeneity, and small sample size in included studies. CONCLUSIONS: Overall, responsive feeding may decrease in-hospital weight gain. Although the evidence is very uncertain, responsive feeding may slightly decrease the duration of hospitalization. Evidence was insufficient to understand the effects of responsive compared with scheduled feeding on mortality, morbidity, linear growth, and neurodevelopmental outcomes in preterm and LBW infants. [ABSTRACT FROM AUTHOR]

Copper iodide (CuI) is a promising material for use as hole‐transport layers in electronic devices due to their solution processability and efficient hole conductivity. CuI has a rich chemistry with halide salts and solvents to which it may be exposed during device fabrication. Thus, care must be taken during device fabrication when CuI is used. We present a study using CuI as a hole transport layer in a p‐i‐n perovskite photovoltaic architecture. We studied how each of the components present in the perovskite precursor solution impacts the integrity of CuI films using power x‐ray diffraction, UV‐vis spectroscopy and impedance spectroscopy. Based on these studies, we show that DMSO, mixtures of γ‐butyrolactone:DMSO (v/v 7 : 3) and DMF:DMSO (v/v 8 : 2), and iodide ions can dissolve the CuI layer. We also how that by coating a layer of copper(II) acetate and utilizing the known Cu(II)/Cu(I) redox chemistry with iodide ions, we can preserve CuI in the presence of halide salts and solvents. [ABSTRACT FROM AUTHOR]

Enterotoxigenic Escherichia coli (ETEC) is a primary causative agent of diarrhea in travelers and young children in low-to-middle-income countries (LMICs). ETEC adhere to intestinal epithelia via colonization factors (CFs) and secrete heat-stable toxin (ST) and/or heat-labile toxin (LT), causing dysregulated cellular ion transport and water secretion. ETEC isolates often harbor genes encoding more than one CF that are targets as vaccine antigens. CFA/I is a major CF that is associated with ETEC that causes moderate-to-severe diarrhea and plays an important role in pathogenesis. The Global Enteric Multicenter Study finding that 78% of CFA/I-expressing ETEC also encode the minor CF CS21 prompted investigation of the combined role of these two CFs. Western blots and electron microscopy demonstrated growth media-dependent and strain-dependent differences in CFA/I and CS21 expression. The critical role of CFA/I in adherence by ETEC strains expressing CFA/I and CS21 was demonstrated using the human enteroid model and a series of CFA/I- and CS21-specific mutants. Furthermore, only anti-CFA/I antibodies inhibited adherence by global ETEC isolates expressing CFA/I and CS21. Delivery of ST and resulting cGMP secretion was measured in supernatants from infected enteroid monolayers, and strain-specific ST delivery and time-dependent cGMP production was observed. Interestingly, cGMP levels were similar across wildtype and CF-deficient strains, reflecting a limitation of this static aerobic infection model. Despite adherence by ETEC and delivery of ST, the enteroid monolayer integrity was not disrupted, as shown by the lack of decrease in transepithelial electrical resistance and the lack of IL-8 cytokines produced during infection. Taken together, these data demonstrate that targeting CFA/I in global clinical CFA/I-CS21 strains is sufficient for adherence inhibition, supporting a vaccine strategy that focuses on blocking major CFs. In addition, the human enteroid model has significant utility for the study of ETEC pathogenesis and evaluation of vaccine-induced functional antibody responses. Author summary: Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea in travelers and in young children in low-to-middle-income countries (LMIC). ETEC infects the small intestine using surface located adhesins called colonization factors (CFs) and delivers toxins to the intestine. These CFs are optimal targets for ETEC vaccine development for the induction of colonization-blocking responses. In the current study we investigated the role of 2 CFs, namely CFA/I and CS21 when they are simultaneously expressed in geographically diverse ETEC clinical isolates, in infection using the human enteroid model. This system is the most human relevant and sensitive model to study enteric pathogens. We determined that CFA/I was important for adherence to the human enteroid by ETEC strains expressing CFA/I and CS21. Strain-specific levels of toxin delivery were quantified but there was no difference between wildtype and CF-deficient mutant strains. This result highlights the opportunity to consider the effects of intestinal movement and oxygen levels in the model. Infected enteroids did not have disrupted cell monolayers or produce inflammatory signals. This study supports the strategy to target CFA/I in ETEC vaccine development and underscores the enteroid as a significant model system. [ABSTRACT FROM AUTHOR]

We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis. [ABSTRACT FROM AUTHOR]

Mapping accessible chromatin across time scales can give insights into its dynamic nature, for example during cellular differentiation and tissue or organism development. Analysis of such data can be utilised to identify functional cis-regulatory elements (CRE) and transcription factor binding sites and, when combined with transcriptomics, can reveal gene regulatory networks (GRNs) of expressed genes. Chromatin accessibility mapping is a powerful approach and can be performed using ATAC-sequencing (ATACseq), whereby Tn5 transposase inserts sequencing adaptors into genomic DNA to identify differentially accessible regions of chromatin in different cell populations. It requires low sample input and can be performed and analysed relatively quickly compared with other methods. The data generated from ATAC-seq, along with other genomic approaches, can help uncover chromatin packaging and potential cis-regulatory elements that may be responsible for gene expression. Here, we describe the ATAC-seq approach and give examples from mainly vertebrate embryonic development, where such datasets have identified the highly dynamic nature of chromatin, with differing landscapes between cellular precursors for different lineages. [ABSTRACT FROM AUTHOR]

Discrepancies in multi-informant reports of parenting practices represent a meaningful clinical construct that can be harnessed to predict adolescent mental health outcomes and shed light on the nature of parent-adolescent relationships. To date, however, no research has sought to examine discrepancies in perceptions of parenting practices among adolescents with histories of substance use disorders, a population for whom supportive parenting is a critical protective factor during the recovery process. This study examined parent-adolescent informant discrepancies of parenting practices and their associations with externalizing and internalizing symptomology among a sample of adolescents with substance use disorder histories. Data were analyzed from 294 adolescents (M adolescent age = 16 years; 45% female, 72% white) and their parents (87% female, 83% white) from a larger longitudinal study. Parenting practices of interest were positive parenting, inconsistent discipline, and poor monitoring. Polynomial regression analyses were used to test the discrepancy hypotheses. The results generally suggested null associations between single informant reports and internalizing and externalizing symptoms. Discrepancies were noted, however, in multi-informant reports of positive parenting, such that higher levels of adolescent-reported positive parenting were associated with higher levels of internalizing symptoms at high (but not low) levels of parent-reported positive parenting. Similarly, discrepancies were noted in multi-informant reports of poor monitoring, such that lower levels of adolescent-poor monitoring were associated with higher externalizing symptoms at low levels of parent-reported poor monitoring. The findings are discussed in terms of research and clinical implications of collecting and utilizing multi-informant data among clinical samples of adolescents with unique risk profiles. [ABSTRACT FROM AUTHOR]

Aim: To develop a valid, reliable research instrument to measure mechanisms associated with organisational learning in hospitals. Background: A valid, reliable instrument for measuring mechanisms of organisational learning would enable nurse leaders and researchers to improve health care through facilitation and study of organisational learning. Methods: The Organizational Learning in Hospitals model was used as a framework to develop the Organizational Learning Instrument‐Mechanisms. Cognitive interviews and expert reviews were used to refine and evaluate item‐level and scale‐level content validity. The instrument was distributed by email to a random sample of nurses working in inpatient hospitals in Utah (n = 1253). Confirmatory factor analysis was used to assess construct validity, and coefficient alpha was used to assess internal reliability. Results: Item‐level content validity scores were.88 to 1.0, and scale‐level content validity was.98 (maximum score = 1.0). Standardized factor loadings were.539–.956, with model fit statistics as follows: comparative fit index (CFI) =.975, Tucker–Lewis index (TLI) =.973 and root mean square error of approximation (RMSEA) =.059. Coefficient alpha scores were.77–.95 for the instrument's five factors. Conclusions: Initial testing indicates the Organizational Learning Instrument‐Mechanisms has adequate levels of reliability, content validity and construct validity. Implications for Nursing Management: Hospital leaders and researchers may begin using this instrument to improve and study the mechanisms of organisational learning in hospital units. [ABSTRACT FROM AUTHOR]

The article analyze the deliberative practices embedded in the FTNT initiative, identifying the ways in which this program was designed for. Topics discussed including explore FTNT's many venues of outreach in communities statewide, how the archival collection of the program constructs a narrative of civic engagement, and program of historical and rhetorical education for teachers and scholars.

Purpose: Similar to fingerprints, patterned grooves and ridges on the lips are unique to each person and have the potential to aid in human identification. This study analyzed inter-rater reliability among senior dental hygiene students tasked with classifying Cheiloscopy (human lip print) patterns to assess levels of agreement between participants. Methods: Researchers of this human subjects IRB approved study recruited a convenience sample of 50 volunteers and collected their lip prints. Cosmetic lipstick was applied to the volunteers' lips, then cellophane tape was used to retrieve the prints which were transferred to white bond paper for viewing. Following lip print collection, senior dental hygiene students (N=43) were recruited by email and assigned to an experimental group (n=14) who received a 15-minute presentation on Cheiloscopy classification procedures and had practice classifying lip print samples, or the control group (n=13) who did not receive the presentation or practice. Then, all participants were provided the 50 lip print samples to visually analyze and categorize according to the gold standard Suzuki and Tsuchihashi Cheiloscopy classification system. Results: Data collection is currently ongoing. Preliminary results indicated that the Kappa estimates for both groups suggest a fair level of agreement. The level of agreement was higher for the experimental group than the control group (37% vs. 22%), with a statistically significant difference (95% C.I. = (4.2%, 21.1%)). Conclusion: These results suggest that training increases levels of agreement between lip print raters; however, more research is needed on cheiloscopy calibration due to low levels of agreement with or without training. [ABSTRACT FROM AUTHOR]

Meta-analyses that statistically synthesize evidence from multiple research studies can play an important role in advancing evidence-informed prevention science. When done in the context of a well-conducted systematic review, meta-analysis is a powerful tool for synthesizing evidence and exploring research questions that are difficult to address in individual studies, such as the association of individual study limitations on intervention effect estimates, replicability of empirical findings, and variation of effect estimates across populations and settings. Alongside the rapid growth in the number of published reviews and meta-analyses, there has been a parallel growth in the development of meta-analytic techniques to handle the increasingly complex types of questions and types of evidence relevant to prevention science. Despite this rapid evolution of meta-analytic techniques and approaches, there is still a lag between the development of new techniques and their uptake by researchers in the field. This paper serves as a brief introduction to this special issue of Prevention Science, entitled "Modern Meta-Analytic Methods in Prevention Science," which highlights recent developments in meta-analytic methods and demonstrates their application to prevention research. This special issue makes an important contribution to the field by ensuring these methodological advances are widely accessible to prevention science researchers, thereby improving their uptake and utilization, and ultimately improving the utility and rigor of research syntheses for informing evidence-based decision making in prevention. [ABSTRACT FROM AUTHOR]

Aims: To estimate effects of brief substance use interventions delivered in general medical settings. Methods: A systematic review and meta‐analysis of randomized trials conducted since 1990 of brief substance use interventions in patients of any age or severity level recruited in general medical settings. Primary outcomes were any measure of substance use or substance‐related consequences (indexed with Hedges' g and risk ratios). Mixed‐effects meta‐regressions were used to estimate overall effects and predictors of effect variability. Analyses were conducted separately by brief intervention (BI) target substance: alcohol only or drugs. Findings A total of 116 trials (64 439 participants) were identified; 111 (62 263 participants) provided effect size data and were included in the meta‐analysis. Drug‐targeted BIs yielded significant small improvements in multiple drug/mixed substance use (Hedges' g(g¯) = 0.08; 95% CI = 0.002, 0.15), but after adjusting for multiple comparisons, they did not produce significant effects on cannabis use (g¯ = 0.06; 95% CI = 0.001, 0.12), alcohol use (g¯ = 0.08; 95% CI = −0.0003, 0.17), or consequences (g¯ = 0.05; 95% CI = 0.01, 0.10). Drug‐targeted BIs yielded larger improvements in multiple drug/mixed substance use when delivered by a general practitioner (g¯ = 0.19; 95% CI = 0.187, 0.193). Alcohol‐targeted BIs yielded small beneficial effects on alcohol use (g¯ = 0.12; 95% CI 0.08, 0.16), but no evidence of an effect on consequences (g¯ = 0.05; 95% CI = −0.04, 0.13). However, alcohol‐targeted BIs only had beneficial effects on alcohol use when delivered in general medical settings (g¯ = 0.17; 95% CI = 0.10, 0.24); the findings were inconclusive for those delivered in emergency department/trauma centers (g¯ = 0.05; 95% CI = 0.00, 0.10). Conclusions: When delivered in general medical settings, alcohol‐targeted brief interventions may produce small beneficial reductions in drinking (equivalent to a reduction in 1 drinking day per month). There is limited evidence regarding the effects of drug‐targeted brief interventions on drug use. [ABSTRACT FROM AUTHOR]

Background: Video magnification (VM) is a useful tool often employed in low vision rehabilitation (LVR), particularly when conventional magnification options are unable to fulfill a patient's reading goals. VM offers an alternative solution to overcoming the limitations of traditional low vision (LV) aids. Portability is an important feature that can extend the use of these devices into multiple settings and tasks. As with any LV aid, every portable VM device will have pros and cons that should be considered when prescribing. Case Reports: Five cases are discussed illustrating the application of a systematic approach to prescribing portable VM devices for LV patients with various levels of visual impairment. Standard measures of visual function, including visual acuity (VA), visual fields (VF), and contrast sensitivity, were reduced to different extents in each case. All patients communicated a chief complaint of decreased reading performance. Primary goals covered included spot reading, recreational volume reading, and vocational reading. These goals were all successfully met by carefully matching each patient's reading goals with a specific type and model of a portable VM device. Conclusion: Handheld VM devices offer a portable and adaptable solution for addressing a LV patient's reading needs, thereby making these devices appealing to both the LV provider and the patient. However, with such a large array of portable electronic magnifiers available on the market, the task of prescribing the most appropriate device for the LV patient can be challenging. A systematic LVR approach assessing all of the factors that may influence a patient's success with a portable VM device can ease the selection process. This paper will provide an overview of the vast number of options of portable VM devices available, review the patient and device selection criteria utilized for determining the most appropriate one, and demonstrate practical application of these devices in LVR through case presentation. [ABSTRACT FROM AUTHOR]

US military Veterans are at greater risk for suicide than those who have never served in the US military. Recent federal calls include the need to investigate military-specific suicide risk and protective factors among military-affiliated populations. To date, no study has examined the link between military identity, self-stigma, and suicide risk. The current study used a nationally representative sample of post-Vietnam US military Veterans (N = 1,461) in order to determine relationships between military identity, self-stigma, and suicide risk. Idealism (OR = 0.86) with less odds of elevated suicide risk, whereas individualism (OR = 1.15) and military self-stigma (OR = 1.39) were associated with increased odds of elevated suicide risk. Military self-stigma was found to mediate the relationship between military identity components and suicide risk. Implications for conceptualization of military Veteran identity, suicide prevention, and future research are discussed. [ABSTRACT FROM AUTHOR]

• The prior attempt risk group reported significantly higher rates of interpersonal violence than the ideation only group. • Teacher support, peer interactions, and neighborhood social connection buffered the association between sexual abuse and prior attempts. • Neighborhood social connection buffered the association between physical abuse and prior suicide attempts. • Tailored efforts to enhance social connectedness in youth exposed to violence could be a promising secondary suicide prevention strategy. Exposure to interpersonal violence is associated with elevated suicide risk. Preventing suicide among high-risk adolescents is most often discussed from a clinical treatment perspective, resulting in a gap in research examining whether school and community connectedness can buffer the relationships between forms of interpersonal violence and suicide risk in clinical samples of adolescents. Baseline data from 294 adolescents who received substance use treatment were analyzed to help fill this gap in research. Adolescents in this sample were at greater risk for suicidal thoughts and behaviors given their histories of substance use disorders and high rates of interpersonal violence, with 57% reporting experiencing at least one form of abuse/violence. Independent variables included lifetime exposure to physical abuse, sexual abuse, and weapon violence; moderators included various measures of school and community connectedness. Multinomial logistic regression models were estimated to examine the main and interaction effects predicting a three-category measure of suicide risk: non-suicidal, suicidal ideation only, and prior suicide attempts. Sexual abuse survivors had the highest predicted probability of a prior suicide attempt when reporting lower levels of teacher support, school-based positive peer interactions, or neighborhood social connection, but at higher levels of these protective factors, their predicted probability was similar to those not exposed to sexual abuse. The same protective pattern was observed for physical abuse survivors with high neighborhood social connection. The buffering effects observed in this study identified dimensions of school and community social connectedness as protective factors for youth exposed to abuse. Although promoting social connectedness is often cited as a universal suicide prevention approach, tailored efforts to enhance connectedness within this population may also be a promising secondary prevention strategy. Thus, in addition to clinical treatment, more emphasis should be placed on systems-level approaches to reducing risk among youth most vulnerable to suicide. [ABSTRACT FROM AUTHOR]

Objective: Dually diagnosed adolescents are a high-risk population for experiencing suicidal thoughts and behavior. Given that research suggests risk factors for suicidal ideation and suicide attempts may be different, this study examined whether internalizing disorder severity, frequency of substance use, and the interaction between them differentiated adolescents who attempted suicide from those who ideated. Methods: Baseline data from 287 adolescents who received formal substance use disorder (SUD) treatment were used in this analysis. Major depressive disorder (MDD) and generalized anxiety disorder (GAD) severity as well as past-3 month use of alcohol, cannabis, and other illicit drugs were considered. The outcome of interest was a three-category measure of suicide risk: no reported suicidal ideation or attempts, suicidal ideation only, and suicide attempts. Results: Over half of the sample disclosed prior suicidal ideation (30.0%) or attempts (27.9%). Multinomial logistic regression models indicated more severe MDD and GAD symptomology differentiated ideators from non-suicidal adolescents, but internalizing disorder severity did not differ between ideators and attempters. Substance use frequency did not differ between suicide risk groups. MDD severity and frequency of alcohol use interacted to increase the risk of attempts, yet the effects were minimal. Instead, prior weapon violence victimization and sexual abuse were the largest differentiators between attempters and ideators. Conclusions: Findings suggest that internalizing disorder severity and prior traumatic experiences put adolescents with SUD histories at higher risk of suicidal thoughts and behaviors. Thus, integrating evidence-based suicide prevention and intervention efforts into SUD treatment is critical, particularly for dually diagnosed adolescents who meet these risk profiles. Psychotherapy and medication may help curtail the development of ideation by reducing symptoms of MDD and GAD, whereas adolescents with prior traumatic experiences may benefit from additional treatments shown to lower risk of suicide attempts. [ABSTRACT FROM AUTHOR]

Background: Symmetric drug‐related intertriginous and flexural exanthema (SDRIFE) is a cutaneous drug reaction characterized by gluteal/anogenital erythema and symmetric involvement of other intertriginous location(s) without systemic signs. Clinicopathologic characterization has been limited to case reports and small series. We describe 19 new cases and review the literature to better define the clinical and histopathologic spectrum of SDRIFE. Methods: Pathology archives were searched for "SDRIFE" and "baboon syndrome." Cases meeting clinical criteria were included. Clinical and histopathologic features were recorded. Previous reports of SDRIFE with histopathologic descriptions were reviewed. Results: Nineteen new cases were included, over half triggered by antibiotics. Six new causative medications were identified. Median onset was 7 days. Typical lesions were erythematous plaques or papules with or without scale. The most common histopathologic finding was superficial perivascular lymphocytic infiltrate followed by dermal eosinophils, spongiosis, and orthokeratosis. Basal vacuolization and apoptotic keratinocytes were less common. Interstitial histiocytes were present in almost half of our cases. Other findings included atypical lymphocytes and "flame figure." Conclusions: Appreciation of the range of inciting medications and clinicopathologic features in SDRIFE will improve recognition of this condition. Although many histopathologic features overlap with other common dermatitides, biopsy may assist in excluding key clinical mimics. [ABSTRACT FROM AUTHOR]

Merkel cell carcinoma (MCC) is a rare, but aggressive skin cancer the incidence of which has increased significantly in recent years. The majority of MCCs have incorporated Merkel cell polyomavirus (VP-MCC) while the remainder are virus-negative (VN-MCC). Although a variety of therapeutic options have shown promise in treating MCC, there remains a need for additional therapeutics as well as probes for better understanding MCC. A high-throughput screening campaign was used to assess the ability of > 25,000 synthetic and natural product compounds as well as > 20,000 natural product extracts to affect growth and survival of VN-MCC and VP-MCC cell lines. Sixteen active compounds were identified that have mechanisms of action reported in the literature along with a number of compounds with unknown mechanisms. Screening results with pure compounds suggest a range of potential targets for MCC including DNA damage, inhibition of DNA or protein synthesis, reactive oxygen species, and proteasome inhibition as well as NFκB inhibition while also suggesting the importance of zinc and/or copper binding. Many of the active compounds, particularly some of the natural products, have multiple reported targets suggesting that this strategy might be a particularly fruitful approach. Processing of several active natural product extracts resulted in the identification of additional MCC-active compounds. Based on these results, further investigations focused on natural products sources, particularly of fungal origin, are expected to yield further potentially useful modulators of MCC. [ABSTRACT FROM AUTHOR]

Objective: Although a relationship between schizophrenia (SCZ), antipsychotic (AP) medication, and metabolic dysregulation is now well established, the effect of adiposity is less well understood. By synthesizing findings from imaging techniques that measure adiposity, our systematic review and meta‐analysis (PROSPERO CRD42020192977) aims to determine the adiposity‐related effects of illness and treatment in this patient population. Methods: We searched MEDLINE, EMBASE, PsychINFO and Scopus for all relevant case‐control and prospective longitudinal studies from inception until February 2021. Measures of adiposity including percent body fat (%BF), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) were analyzed as primary outcomes. Results: Our search identified 29 articles that used imaging methods to quantify adiposity among patients with SCZ spectrum disorders. Analyses revealed that patients have greater %BF (mean difference (MD) = 3.09%; 95% CI: 0.75–5.44), SAT (MD = 24.29 cm2; 95% CI: 2.97–45.61) and VAT (MD = 33.73 cm2, 95% CI: 4.19–63.27) compared to healthy controls. AP treatment was found to increase SAT (MD = 31.98 cm2; 95% CI: 11.33–52.64) and VAT (MD = 16.30 cm2; 95% CI: 8.17–24.44) with no effect on %BF. However, change in %BF was higher for AP‐free/AP‐naïve patients compared to treated patients. Conclusion: Our findings indicate that patients with SCZ spectrum disorders have greater adiposity than healthy controls, which is increased by AP treatment. Young, AP‐naïve patients may be particularly susceptible to this effect. Future studies should explore the effect of specific APs on adiposity and its relation to overall metabolic health. [ABSTRACT FROM AUTHOR]

Background: Stunting, an indicator of restricted linear growth, has become a primary measure of childhood undernutrition due to its persistent high prevalence globally, and importance for health and development. Although the etiology is recognized as complex, most analyses have focused on social and biomedical determinants, with limited attention on psychological factors affecting care and nurturing in the home. We assessed whether the psychological distress of parents is related to child linear growth and stunting, and documented the associated risk factors, and examined the relationship between parental distress and behavioral and other risk factors for stunting. Methods: We used data from the Indonesia National Health Survey 2013, including 46,315 children 6–59 months of age. Multivariate linear, logistic, and multilevel multinomial logistic regression, using survey weights, were used to assess the relationship between parental distress, as assessed by the WHO Self Reporting Questionnaire (SRQ20), with height-for-age z score (HAZ), stunting, and behavioral and other risk factors for stunting. Results: Maternal, paternal and parental distress (i.e. both maternal and paternal distress) were associated with reduced linear growth of the children by 0.086 (95% CI -0.17, -0.00), 0.11 (95% CI -0.24, -0.02) and 0.19 (95% CI -0.37, -0.00) HAZ-scores, respectively. Maternal and paternal distress increased the risk of mild stunting (HAZ <-1) by 33% (95% CI 1.17,1.50) and 37% (95% CI 1.18,1.60), and the risk of moderate stunting (HAZ <-2) by 25% (95% CI 1.10,1.43) and 28% (95% CI 1.08,1.51]), respectively. Parental stress increased the risk of moderate stunting by 40% (95% CI 1.06,1.85). Amongst specific groups of risk factors, the proportion of HAZ-score lost was associated with socioeconomic factors (30.3%) including, low wealth, low maternal occupational status, low maternal education, rural residence, and low paternal occupational status; physiological factors (15.5%) including low maternal height, low maternal mid-upper arm circumference, being male, low paternal height; behavioral factors (8.9%) including open garbage disposal, paternal smoking, not using iodized salt; and experiencing at least one infectious diseases episode (1.1%). Conclusions: Maternal, paternal and parental stress were associated with reduced linear growth of children. These findings highlight the complex etiology of stunting and suggest nutritional and other biomedical interventions are insufficient, and that promotion of mental and behavioral health programs for parents must be pursued as part of a comprehensive strategy to enhance child growth and development, i.e. improved caretaker capacity, integrated community development, improved parenting skills, as well as reduced gender discrimination, and domestic violence. [ABSTRACT FROM AUTHOR]

The article presents a research report on limited data exist to inform our basic understanding of micronutrient requirements in pregnancy. Topics include women and pregnant people have historically been underrepresented in research extend to the basic research informing nutrient reference values; and nutrient reference values are intended for use in population that basic science informing values with funders and researchers to address fundamental gaps in knowledge with high-quality research.

Aquatic invasions are a major ecological and socio-economic concern. Management of invasive aquatic populations requires a robust understanding of the effectiveness and suitability of control methods. In this review, we consider multiple control options for the management of invasive aquatic amphipods, exploring their efficacy and application constraints. Technological opportunities (pheromone, RNAi, biotechnologies) and gaps in our understanding around control mechanisms are identified, with the aim to improve management success of this order. Within this review, the UK invasion of the killer shrimp, Dikerogammarus villosus (Sowinsky, 1894) is used as a case study of the best explored example of invasive amphipod control. This species has had a range of ecological, physiological, pathological, and experimental research conducted upon it, which is highlighted from a management perspective. This same data, where available, has been synthesised for 46 other invasive amphipods, to probe for weaknesses that future management methods can exploit and be developed around. Successful management examples for invasive amphipod species remain rare. A lack of currently available tested options severely limits the possibility for amphipod management, post establishment. For future management to be successful, further work is needed to develop targeted and specific control methods, which ideally, are cost effective, have no/little associated ecological impacts, and can be broadly applied in closed and open water systems. Our synthesis presents opportunities for the further, informed development of control systems for invasive amphipods. [ABSTRACT FROM AUTHOR]

Purpose: Postural tachycardia syndrome (POTS), a syndrome characterized by orthostatic symptoms and a heart rate increase of at least 30 beats per minute in the absence of hypotension upon standing, is often accompanied by increased sympathetic activity and low blood volume. A common non-pharmacologic recommendation for patients with POTS is a high-sodium (HS) diet with the goal of bolstering circulating blood volume. The objective of this study is to assess the effects of 6 days of a HS diet on endothelial function in POTS. Methods: A total of 14 patients with POTS and 13 age-matched healthy controls, all females, were studied following 6 days on a low-sodium (LS) diet (10 mEq/day) and 6 days on a HS diet (300 mEq/day) in a crossover design. We measured endothelial function following reactive hyperemia in the brachial artery using flow-mediated dilation (FMD), leg blood flow (LBF) using strain gauge plethysmography in the calf, and reactive hyperemic index (RHI) in the microcirculation of the hand using pulsatile arterial tonometry. Results: On the LS diet, FMD% did not differ between patients with POTS and the healthy controls although peak brachial artery diameter was lower for the patient group. RHI was higher for the patient group than for the controls, but there were no differences in post-ischemic LBF increase. On the HS diet, there were no between-group differences in FMD%, LBF increase, or RHI. Conclusion: In summary, a HS diet for 6 days did not induce endothelial dysfunction. This non-pharmacologic treatment used for patients with POTS does not negatively affect endothelial function when used for a sub-acute duration. Trial registration: ClinicalTrials.gov NCT01550315; March 9, 2012. [ABSTRACT FROM AUTHOR]

There is an urgent need to better understand the micronutrient demands of pregnancy due to the complex physiological adaptations during the gestational period and the importance of micronutrients in maternal-fetal health. Rigorous studies of micronutrients in pregnancy are significantly lacking due to a number of issues including the exclusion of pregnant people in research, methodological barriers to studying micronutrients, and the multidisciplinary expertise required for such studies. Stable isotopes present a unique methodological opportunity to quantify pregnancy-related changes in the absorption, distribution, metabolism, and excretion of micronutrients. We demonstrate here through a rapid review of the published literature that this approach is dramatically underutilized outside of calcium. In this perspective, we discuss the use of stable isotopes to study micronutrient physiology and our experiences in addressing the need for more studies in this area. Finally, we discuss how we might overcome major barriers to move toward a better understanding of micronutrient physiology in pregnancy. [ABSTRACT FROM AUTHOR]

We address two aims: Aim 1 (Fitness Review) compares the effect of higher cardiorespiratory fitness (CRF) (e.g., endurance athletes) with lower CRF (e.g., sedentary adults) on cerebrovascular outcomes, including middle cerebral artery velocity (MCAv), cerebrovascular reactivity and resistance, and global cerebral blood flow, as assessed by transcranial Doppler (TCD) or magnetic resonance imaging (MRI). Aim 2 (Exercise Training Review) determines the effect of exercise training on cerebrovascular outcomes. Systematic review of studies with meta-analyses where appropriate. Certainty of evidence was assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Twenty studies (18 using TCD) met the eligibility criteria for Aim 1, and 14 studies (8 by TCD) were included for Aim 2. There was a significant effect of higher CRF compared with lower CRF on cerebrovascular resistance (effect size = -0.54, 95% confidence interval = -0.91 to -0.16) and cerebrovascular reactivity (0.98, 0.41-1.55). Studies including males only demonstrated a greater effect of higher CRF on cerebrovascular resistance than mixed or female studies (male only: -0.69, -1.06 to -0.32; mixed and female studies: 0.10, -0.28 to 0.49). Exercise training did not increase MCAv (0.05, -0.21 to 0.31) but showed a small nonsignificant improvement in cerebrovascular reactivity (0.60, -0.08 to 1.28; P = 0.09). Exercise training showed heterogeneous effects on regional but little effect on global cerebral blood flow as measured by MRI. High CRF positively effects cerebrovascular function, including decreased cerebrovascular resistance and increased cerebrovascular reactivity; however, global cerebral blood flow and MCAv are primarily unchanged following an exercise intervention in healthy and clinical populations. [ABSTRACT FROM AUTHOR]