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Purpose of Review As maternal mortality climbs in the USA with mental health conditions driving these preventable deaths, the field of reproductive psychiatry must shift towards identification of women and other birthing individuals at risk and facilitating access. This review brings together recent studies regarding risk of perinatal depression and highlights important comorbidities that place individuals at higher vulnerability to poor perinatal outcomes. Recent Findings Recent research suggests that identifying risk for perinatal depression including historical diagnoses of depression, anxiety, trauma, and comorbid substance use and intimate partner violence may move the field to focus on preventive care in peripartum populations. Emerging data shows stark health inequities in racial and ethnic minority populations historically marginalized by the health system and in other vulnerable groups such as LGBTQ+ individuals and those with severe mental illness. Summary Innovative models of care using systems-level approaches can provide opportunities for identification and risk analyses of vulnerable peripartum patients and facilitate access to therapeutic or preventive interventions. Utilizing intergenerational approaches and leveraging multidisciplinary teams that thoughtfully target high-risk women and other birthing individuals could promote significant changes to population-level care in maternal health.

Background: Military sexual trauma (MST) that involves assault is associated with poorer sexual function in U. S. women service members/veterans (SM/Vs). Theory of sexual function suggests that the presence of higher depression severity and more negative sexual self-schemas may contribute to sexual dysfunction. This has yet to be examined in partnered women SM/Vs who are survivors of MST. Objective: Using path analysis, the current study examined the associations of MST type, depression, sexual self-schemas, and sexual function in 818 partnered women SM/Vs. Method: Three separate mediation models were tested, all testing indirect effects of depression and sexual self-schemas on the association of MST type and sexual function. In Model 1, the mediation model assumed that exposure to MST predicted more severe depression, which then predicted more negative sexual self-schemas. More negative sexual self-schemas, in turn, predicted poorer sexual function. In Model 2, the mediation model assumed that exposure to MST predicted more negative sexual self-schemas, which then predicted more severe depression. More severe depression, in turn, predicted poorer sexual function. In Model 3, the mediation model assumed a parallel mediation in that exposure to MST predicted more severe depression and more negative sexual self-schemas, which in turn, predicted poorer sexual function. Results: The best fitting model suggested a parallel mediation of higher depression severity (estimate: −1.30, confidence interval: −1.91,-.69) and more negative sexual self-schemas (estimate: −2.09, confidence interval: −2.94,-1.24) on the association of assault MST and poorer sexual function (Model 3). Harassment-only MST was unrelated to sexual function through mediated pathways. Conclusions: Interventions to improve sexual function among MST survivors who experienced assault should address negative sexual self-schemas related to sexual performance and depressive symptoms. Cognitive behavioural interventions that include challenging maladaptive cognitions may be well suited to address this clinical need. Mechanisms of poor sexual function in military sexual trauma (MST) survivors are under-studied. Depression and sexual self-schemas mediated this association in assault survivors. Cognitive behavioral therapies that challenge maladaptive cognitions may decrease sexual dysfunction.

Objectives To examine with a parallel group study design the performance and physiological responses to a 14-day off-season ‘live high-train low in the heat’ training camp in elite football players. Methods Seventeen professional Australian Rules Football players participated in outdoor football-specific skills (32±1°C, 11.5 h) and indoor strength (23±1°C, 9.3 h) sessions and slept (12 nights) and cycled indoors (4.3 h) in either normal air (NORM, n=8) or normobaric hypoxia (14±1 h/day, FiO2 15.2–14.3%, corresponding to a simulated altitude of 2500–3000 m, hypoxic (HYP), n=9). They completed the Yo-Yo Intermittent Recovery level 2 (Yo-YoIR2) in temperate conditions (23±1°C, normal air) precamp (Pre) and postcamp (Post). Plasma volume (PV) and haemoglobin mass (Hbmass) were measured at similar times and 4 weeks postcamp (4WPost). Sweat sodium concentration ((Na+)sweat) was measured Pre and Post during a heat-response test (44°C). Results Both groups showed very large improvements in Yo-YoIR2 at Post (+44%; 90% CL 38, 50), with no between-group differences in the changes (−1%; −9, 9). Postcamp, large changes in PV (+5.6%; −1.8, 5.6) and (Na+)sweat (−29%; −37, −19) were observed in both groups, while Hbmass only moderately increased in HYP (+2.6%; 0.5, 4.5). At 4WPost, there was a likely slightly greater increase in Hbmass (+4.6%; 0.0, 9.3) and PV (+6%; −5, 18, unclear) in HYP than in NORM. Conclusions The combination of heat and hypoxic exposure during sleep/training might offer a promising ‘conditioning cocktail’ in team sports.

Neonatal hemophagocytic lymphohistiocytosis (HLH) is a medical emergency that can be associated with significant morbidity and mortality. Often these patients present with familial HLH (f-HLH), which is caused by gene mutations interfering with the cytolytic pathway of cytotoxic T-lymphocytes (CTLs) and natural killer cells. Here we describe a male newborn who met the HLH diagnostic criteria, presented with profound cholestasis, and carried a maternally inherited heterozygous mutation in [ , c.568C>T (p.Arg190Cys)] in addition to a severe pathogenic variant in [ , hemizygous c.1153T>C (Cys385Arg)]. Although mutations in gene are associated with f-HLH type 5, the clinical and biological relevance of the p.Arg190Cys mutation identified in this patient was uncertain. To assess its role in disease pathogenesis, we performed functional assays and biochemical and microscopic studies. We found that p.Arg190Cys mutation did not alter the expression or subcellular localization of STXBP2 or STX11, neither impaired the STXBP2/STX11 interaction. In contrast, forced expression of the mutated protein into normal CTLs strongly inhibited degranulation and reduced the cytolytic activity outcompeting the effect of endogenous wild-type STXBP2. Interestingly, arginine 190 is located in a structurally conserved region of STXBP2 where other f-HLH-5 mutations have been identified. Collectively, data strongly suggest that STXBP2-R190C is a deleterious variant that may act in a dominant-negative manner by probably stabilizing non-productive interactions between STXBP2/STX11 complex and other still unknown factors such as the membrane surface or Munc13-4 protein and thus impairing the release of cytolytic granules. In addition to the contribution of STXBP2-R190C to f-HLH, the accompanied mutation may have compounded the clinical symptoms; however, the extent by which deficiency has contributed to HLH in our patient remains unclear.

Older age consistently relates to a lesser ability to fully recover from a traumatic brain injury (TBI); however, there is limited data to explicate the nature of age-related risks. This study was undertaken to determine the relationship of age on gene-activity following a TBI, and how this biomarker relates to changes in neuroimaging findings. A young group (between the ages of 19 and 35 years), and an old group (between the ages of 60 and 89 years) were compared on global gene-activity within 48 h following a TBI, and then at follow-up within 1-week. At each time-point, gene expression profiles, and imaging findings from both magnetic resonance imaging (MRI) and computed tomography were obtained and compared. The young group was found to have greater gene expression of inflammatory regulatory genes at 48 h and 1-week in genes such as basic leucine zipper transcription factor 2 (BACH2), leucine-rich repeat neuronal 3 (LRRN3), and lymphoid enhancer-binding factor 1 (LEF1) compared to the old group. In the old group, there was increased activity in genes within S100 family, including calcium binding protein P (S100P) and S100 calcium binding protein A8 (S100A8), which previous studies have linked to poor recovery from TBI. The old group also had reduced activity of the noggin (NOG) gene, which is a member of the transforming growth factor-β superfamily and is linked to neurorecovery and neuroregeneration compared to the young group. We link these gene expression findings that were validated to neuroimaging, reporting that in the old group with a MRI finding of TBI-related damage, there was a lesser likelihood to then have a negative MRI finding at follow-up compared to the young group. Together, these data indicate that age impacts gene activity following a TBI, and suggest that this differential activity related to immune regulation and neurorecovery contributes to a lesser likelihood of neuronal recovery in older patients as indicated through neuroimaging.

Constitutive activation of the JAK/STAT3 pathway is a major contributor to oncogenesis. In the present study, structure–activity relationship (SAR) studies with five cucurbitacin (Cuc) analogs, A, B, E, I, and Q, led to the discovery of Cuc Q, which inhibits the activation of STAT3 but not JAK2; Cuc A which inhibits JAK2 but not STAT3 activation; and Cuc B, E, and I, which inhibit the activation of both. Furthermore, these SAR studies demonstrated that conversion of the C3 carbonyl of the cucurbitacins to a hydroxyl results in loss of anti-JAK2 activity, whereas addition of a hydroxyl group to C11 of the cucurbitacins results in loss of anti-STAT3 activity. Cuc Q inhibits selectively the activation of STAT3 and induces apoptosis without inhibition of JAK2, Src, Akt, Erk, or JNK activation. Furthermore, Cuc Q induces apoptosis more potently in human and murine tumors that contain constitutively activated STAT3 (i.e., A549, MDA-MB-435, and v-Src/NIH 3T3) as compared to those that do not (i.e., H-Ras/NIH 3T3, MDA-MB-453, and NIH 3T3 cells). Finally, in a nude mouse tumor xenograft model, Cuc Q, but not Cuc A, suppresses tumor growth indicating that JAK2 inhibition is not sufficient to inhibit tumor growth and suggesting that the ability of Cuc Q to inhibit tumor growth is related to its anti-STAT3 activity. These studies further validate STAT3 as a drug discovery target and provide evidence that pharmacological agents that can selectively reduce the P-STAT3 levels in human cancer cells result in tumor apoptosis and growth inhibition.

Background Sexual violence (SV) and intimate partner violence (IPV) experiences are major social determinants of adverse health. There is limited prevalence data on these experiences for veterans, particularly across sociodemographic groups. Objective To estimate the prevalence of SV before, during, and after military service and lifetime and past-year IPV for women and men, and explore differences across sociodemographic groups. Design Data are from two national cross-sectional surveys conducted in 2020. Weighted prevalence estimates of SV and IPV experiences were computed, and weighted logistic regression models were used for comparisons across gender, race, ethnicity, sexual orientation, and age. Participants Study 1 included veterans of all service eras ( N  = 1187; 50.0% women; 29% response rate). Study 2 included recently separated post-9/11 veterans ( N  = 1494; 55.2% women; 19.4% response rate). Main Measures SV was assessed with the Deployment Risk and Resilience Inventory-2 (DRRI-2). IPV was assessed with the extended Hurt-Insult-Threaten-Scream Tool. Key Results Women were more likely than men to experience pre-military SV (study 1: 39.9% vs. 8.7%, OR = 6.96, CIs: 4.71–10.28; study 2: 36.2% vs. 8.6%, OR = 6.04, CIs: 4.18–8.71), sexual harassment and/or assault during military service (study 1: 55.0% vs. 16.8%, OR = 6.30, CIs: 4.57–8.58; study 2: 52.9% vs. 26.9%, OR = 3.08, CIs: 2.38–3.98), and post-military SV (study 1: 12.4% vs. 0.9%, OR = 15.49, CIs: 6.42–36.97; study 2: 7.5% vs. 1.5%, OR = 5.20, CIs: 2.26–11.99). Women were more likely than men to experience lifetime IPV (study 1: 45.7% vs. 37.1%, OR = 1.38, CIs: 1.04–1.82; study 2: 45.4% and 34.8%, OR = 1.60, CIs: 1.25–2.04) but not past-year IPV (study 1: 27.9% vs. 28.3%, OR = 0.95, CIs: 0.70–1.28; study 2: 33.1% vs. 28.5%, OR = 1.24, CIs: 0.95–1.61). When controlling for gender, there were few differences across other sociodemographic groups, with the exception of sexual orientation. Conclusions Understanding veterans’ experiences of SV and IPV can inform identification and intervention efforts, especially for women and sexual minorities.

Agricultural nutrient losses contribute to hypoxia in the Gulf of Mexico and eutrophication in the Great Lakes. Our objective was to assess effects of topography, geomorphology, climate, cropping systems and land use and conservation practices on hydrology and nutrient fate and transport in the St. Joseph River watershed. We monitored five sites (298 to 4,300 ha [736 to 10,600 ac]) on two drainage ditches within the St. Joseph River watershed in northeastern Indiana. Row crop agriculture, primarily corn ( Zea mays L.) and soybean ( Glycine max [L.] Merr.), is the dominant land use (~60%) in this pothole or closed depression landscape. The hydrology is dominated by subsurface tile drainage supplemented with surface drainage of remote potholes. Vegetative buffer strips have been implemented along >60% of the agricultural drainage ditches. The vegetative buffer strips play an invaluable role protecting water quality though by acting as natural setbacks during fertilizer and pesticide applications. Multiple regressions indicated land cropped to corn and areas with direct drainage or potholes are highly sensitive to nutrient losses. Future conservation assessment efforts in this and similar watersheds should focus on management of potholes in cropped fields and the subsequent effect of those practices on tile drainage water.

Background: The role of palliative resection of the primary tumour in patients who present with metastatic colorectal cancer is unclear. Aims: This study compared the incidence of major intestinal complications in such patients who received chemotherapy treatment with or without prior palliative resection of the primary tumour. Patients: The incidence of intestinal obstruction, perforation, fistula formation, and gastrointestinal haemorrhage, and the requirement for abdominal radiotherapy in patients with metastatic colorectal cancer treated at a single institution over a 10 year period was determined. Results: Eighty two patients received initial treatment with chemotherapy without resection of the primary tumour (unresected group) and 280 patients had undergone prior resection (resected group). In the unresected group, the incidence of peritonitis, fistula formation, and intestinal haemorrhage was 2.4% (95% confidence interval (CI) 0.3–8.5%), 3.7% (95% CI 0.8–10.3%), and 3.7% (95% CI 0.8–10.3%), respectively, and was not significantly different from the resected group. Intestinal obstruction affected 13.4% (95% CI 6.9–22.7%) of patients in the unresected group and 13.2% (95% CI 9.2–17.2%) of patients in the resected group. More patients in the unresected group required ⩾3 blood transfusions (14.6% v 7.5%; p=0.048) and abdominal radiotherapy (18.3% v 9.6%; p=0.03) than the resected group. Conclusions: The incidence of major intestinal complications in patients with unresected colorectal cancer and synchronous metastases who receive initial treatment with chemotherapy is low. Chemotherapy may be successfully used as initial treatment for such patients with no increased risk of most major intestinal complications compared with patients who have undergone initial resection of the primary tumour.

Applications of animal manures have increased soil test P values in many parts of the USA and thus increased the risk that soil P will be transferred to surface water and decrease water quality. To continue farming these areas, landowners need tools to reduce the risk of P losses. A field experiment was conducted near Kurten, TX, on a Zulch fine sandy loam (thermic Udertic Paleustalfs) with Bray-1 P values exceeding 3000 mg P kg(-1) soil (dry wt.) in the A(p) horizon to evaluate the effectiveness of soil amendments for reducing soil test P values. Soils were amended annually from 1999 to 2001 with 1.5 and 5.0 Mg gypsum ha(-1), 1.4 Mg alum ha(-1), or 24.4 Mg ha(-1) of waste paper product high in Al alone or in combination with 1.5 Mg gypsum ha(-1) and/or 1.4 Mg alum ha(-1). These treatments supplied a maximum of 225 and 1163 kg ha(-1) yr(-1) of Al and Ca, respectively. Soil Bray-1 P and dissolved reactive P levels were monitored from 1999 to 2004. None of the soil amendment treatments affected Bray-1 P values. Only annual additions of 5.0 Mg gypsum ha(-1) from 1999 to 2001 significantly reduced soil dissolved reactive P. Dissolved reactive P levels reached minimal levels after two applications of 5.0 Mg gypsum ha(-1) but increased in 2003 and 2004. These results indicate that soil dissolved reactive P levels can be reduced if sufficient amounts of gypsum were added to supply Ca in amounts similar to the soil test P values.