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Dominant negative (DN) mutations in signal transducer and activator of transcription 3 (STAT3) are known to cause hyper-IgE syndrome, a rare primary immunodeficiency. STAT3 DN patients are prone to develop fungal infections, including chronic mucocutaneous candidiasis due to impaired IL-17-mediated immunity, and pulmonary aspergillosis. Despite having preserved phagocyte functions, STAT3 DN patients present connective tissue abnormalities and a defect in the immunological skin barrier. Fusarium species are ubiquitous molds, whose potential to infect humans depends on the host's innate and cellular immune status. Our aim was to describe four STAT3 DN patients with fusariosis confined to the skin. Medical records were reviewed and summarized. Four patients, aged 4, 11, 30, and 33 years, presented with chronic skin lesions which started in the extremities. Two patients had remote lesions, and none had systemic involvement. Skin biopsies showed mycelial threads with deep inflammatory-occasionally granulomatous-infiltrates, reaching the dermis; cultures grew Fusarium solani. Response to treatment was heterogeneous, often requiring multimodal therapies, including topical antifungal preparations. In this work, we describe primary invasive cutaneous fusariosis as a syndromic entity in four STAT3 DN patients.

Threshold collision-induced dissociation of Th(OH)3+(H2O)n (n = 1-4) with xenon was performed using a guided ion beam tandem mass spectrometer. The primary dissociation pathway for all complexes is a loss of a single water molecule followed by the sequential loss of additional water molecules at higher collision energies. The data were analyzed using a statistical model after accounting for lifetime effects and reactant internal and kinetic energy distributions to obtain 0 K bond dissociation energies (BDEs). These were also converted using rigid rotor/harmonic oscillator approximations to yield thermodynamic values at room temperature. The 0 K BDEs of H2O ligands to Th(OH)3+ (IV) are experimentally determined for the first time as 106 ± 6, 89 ± 6, 76 ± 4, and 51 ± 4 kJ/mol for the first, second, third, and fourth water ligand added. These values agree reasonably well with values calculated at the B3LYP, B3PW91, and PBE0 levels of theory with aug-cc-pVQZ basis sets, whereas B3LYP-GD3BJ, MP2, and CCSD(T) single point energies with (without) counterpoise corrections systematically overestimate the bond energies by about 15 (20), 19 (25), and (18) kJ/mol, respectively.

Background and Objectives: Examine trends in opioid prescriptions after laparoscopic sterilization over time, and identify any individual patient, provider, or procedural factors influencing prescribing. Methods: A retrospective observational cohort analysis of laparoscopic sterilizations between January 1, 2016 and December 31, 2019 at Montefiore Medical Center. A review of the medical records was performed and information on patient demographics, comorbid conditions, and surgical characteristics were collected. The number of opioid pills prescribed postoperatively and any pain related patient calls, visits, or refills was recorded. Results: Between January 1, 2016 and December 31, 2019, 615 laparoscopic sterilizations were performed. The median number of opioid pills prescribed was 10, ranging from 0 to 40. There was a significant decrease in the number of opioid pills prescribed (p

Threshold collision-induced dissociation of Th(OH)

Obesity confers an overall increased risk for development of endometrial cancer. However there are conflicting reports regarding the effect of obesity on patients' overall and disease specific survival. The purpose of this study was to evaluate the effect of obesity on survival in women with endometrial cancer.After IRB approval, records of women with diagnosis and treatment of endometrial cancer from 1999 to 2016 were abstracted for histopathological, treatment and demographic data. Death was confirmed by query of the Social Security Death Index. Kaplan Meier survival curves and Cox regression modeling was performed with Stata version 14.0.Of 1732 evaluable patients, there were significant differences in age at diagnosis, histology (endometrioid versus non-endometrioid), stage, race, grade, hypertension, hyperlipidemia, diabetes, and treatment between normal weight, overweight, obese, and morbidly obese patients (p 0.01). There was a linear association of younger age at diagnosis with increasing obesity (p 0.01) RObesity is associated with younger age at diagnosis and earlier stage disease. Obesity is associated with improved disease specific survival for stage 3 and 4 non-endometrioid endometrial cancers.

Both IgCAMs and the actin cytoskeleton play critical roles in neuronal growth cone motility and guidance. However, it is unclear how IgCAM receptors transduce signals from the plasma membrane to induce actin remodeling. Previous studies have shown that local clustering and immobilization of apCAM, the Aplysia homolog of NCAM, induces Src kinase activity and F-actin polymerization in the peripheral domain of cultured Aplysia bag cell growth cones. Therefore, we wanted to test whether the Src kinase substrate and actin regulator cortactin could be a molecular link between Src activity and actin assembly during apCAM-mediated growth cone guidance. Here, we cloned Aplysia cortactin and showed that it is abundant in the nervous system. Immunostaining of growth cones revealed a strong colocalization of cortactin with F-actin in filopodial bundles and at the leading edge of lamellipodia. Perturbation of the cytoskeleton indicated that cortactin distribution largely depends on actin filaments. Furthermore, active Src colocalized with cortactin in regions of actin assembly, including leading edge and filopodia tips. Finally, we observed that cortactin, like F-actin, localizes to apCAM adhesion sites mediating growth cone guidance. Altogether, these data suggest that cortactin is a mediator of IgCAM-triggered actin assembly in the growth cone and involved in motility and guidance.

Recurrent heat waves, already a concern in rapidly growing and urbanizing South Asia, will very likely worsen in a warming world. Coordinated adaptation efforts can reduce heat’s adverse health impacts, however. To address this concern in Ahmedabad (Gujarat, India), a coalition has been formed to develop an evidence-based heat preparedness plan and early warning system. This paper describes the group and initial steps in the plan’s development and implementation. Evidence accumulation included extensive literature review, analysis of local temperature and mortality data, surveys with heat-vulnerable populations, focus groups with health care professionals, and expert consultation. The findings and recommendations were encapsulated in policy briefs for key government agencies, health care professionals, outdoor workers, and slum communities, and synthesized in the heat preparedness plan. A 7-day probabilistic weather forecast was also developed and is used to trigger the plan in advance of dangerous heat waves. The pilot plan was implemented in 2013, and public outreach was done through training workshops, hoardings/billboards, pamphlets, and print advertisements. Evaluation activities and continuous improvement efforts are ongoing, along with plans to explore the program’s scalability to other Indian cities, as Ahmedabad is the first South Asian city to address heat-health threats comprehensively.

Epidemiological studies have indicated the rather significant, yet unclear, impact of sex hormones on cardiovascular physiology and disease. Both observational studies and clinical trials have produced conflicting evidence as to the benefits of female sex hormones, particularly with regards to progesterone. Prolonged exposure to progesterone leads to break-through bleeding, vessel fragility and venous thromboembolisms. Currently, little is known on the molecular and cellular effects of progesterone on the cardiovascular system, or its cell specific functions. In fact, the vascular effects attributed to progesterone have been viewed, for the most part, as secondary consequences of its multiple systemic activities. Using a PRLacZ reporter mouse we have determined that progesterone receptor (PR) expression in the vasculature is restricted to endothelial cells of veins and lymphatics of the reproductive tract. Conditional deletion of PR from endothelial cells using VE-cadherin Cre leads to decreased vascular permeability in the uterus and ovary following treatment with progesterone. Transgenic misexpression of PR in the lung results in pathological vascular leakage and intravascular platelet adhesion in response to progesterone. Additionally, activation of PR within endothelial cells leads to the development of stress fibers, formation of inter-cellular gaps, increased permeability and changes in expression of cell-cell junctional proteins. These results reveal a previously unknown and direct role for PR on endothelial cell function with consequences for physiological permeability, blood vessel integrity and homeostasis.