Impact of Beyond Fistula programming on economic, psychosocial and empowerment outcomes following female genital fistula repair: A retrospective study.

OBJECTIVE: To retrospectively assess changes in economic status, psychosocial status and empowerment among women who participated in Beyond Fistula reintegration programming following fistula repair. METHODS: We conducted a retrospective study among 100 Beyond Fistula program participants capturing sociodemographic characteristics, obstetric and fistula history, program participation, and our primary outcomes: economic status, psychosocial status, and empowerment via quantitative survey at two time points: before program participation and currently. Data were collected from November 2020 to July 2021 from 2013 to 2019 program participants. We compared outcomes across these two time points using paired t tests or McNemar's tests. RESULTS: The proportion of individuals owning property (28.0% vs. 38.0%, P = 0.006), having a current source of income (19.0% vs. 56.0%, P < 0.001), and saving or investing income (11.0% vs. 37.0%, P < 0.001) increased significantly from pre- to post-programming. We also identified statistically significant increases from pre- to post-programming in self-esteem (5.0 [IQR 4.0-5.0] vs. 5.0 [IQR 5.0-5.0], P < 0.001), reintegration (53.0 [IQR 43.0-69.0] vs. 65.0 [IQR 51.0-72.0], P < 0.001) and level of input into household economic decision making (2.0 [SD 1.0] vs. 2.3 [SD 1.0], P = 0.004). CONCLUSION: Beyond Fistula programming likely improved economic status, psychosocial status, and empowerment of participants. Post-surgical interventions incorporating a holistic approach can advance recovery through supporting psychosocial and economic wellbeing and should be offered to women undergoing genital fistula repair.

Effectiveness and cost-effectiveness of an electronic mindfulness-based intervention to improve maternal mental health in the peripartum: study protocol for a randomised controlled trial.

BACKGROUND: Perinatal women are highly vulnerable to developing mental health issues and particularly susceptible to a recurrence of psychiatric illness. Poor mental health during the perinatal period can have long-term impacts on the physical and psychiatric health of both mother and child. A potentially useful strategy to improve women's mental health is through a mobile application teaching mindfulness, an evidence-based technique helping individuals focus on the present moment. METHODS: A mixed method, prospective randomised controlled trial. The study group comprise women aged 18 years and over, who are attending the public and private maternity clinics at Mater Mothers' Hospital. A sample of 360 prenatal women will be randomised into the intervention group (with the use of the mindfulness app) or usual care. Participants will remain in the study for 11 months and will be assessed at four timepoints for changes in postnatal depression, mother-infant bonding, and quality of life. A cost-effectiveness evaluation will also be conducted using quality-adjusted life year (QALY) calculations. A random selection of intervention participants will be invited to attend focus groups to give feedback on the mindfulness app. DISCUSSION: Previous studies have found mindfulness interventions can reduce stress, anxiety, depression, and sleep disturbances in a prenatal population. The risks of the intervention are low, but could be of significant benefit for women who are unable to attend face-to-face appointments due to geographical, financial, or time barriers; during endemic or pandemic scenarios; or due to health or mobility issues. TRIAL REGISTRATION: This study was approved by the Mater Misericordiae Human Research Ethics Committee (83,589). Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12622001581752 ( https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385107&isReview=true ). Registered on 22 Dec. 2022.

Association of Serum Pyridoxal Phosphate Levels with Established Status Epilepticus.

BACKGROUND: The objective of this study was to determine the prevalence of pyridoxine deficiency, measured by pyridoxal phosphate (PLP) levels, in patients admitted to the hospital with established (benzodiazepine-resistant) status epilepticus (SE) (eSE) and to compare to three control groups: intensive care unit (ICU) patients without SE (ICU-noSE), non-ICU inpatients without SE (non-ICU), and outpatients with or without a history of epilepsy (outpatient). METHODS: This retrospective cohort study was conducted at the University of North Carolina Hospitals and Yale New Haven Hospital. Participants included inpatients and outpatients who had serum PLP levels measured during clinical care between January 2018 and March 2021. The first PLP level obtained was categorized as normal (> 30 nmol/L), marginal (≤ 30 nmol/L), deficient (≤ 20 nmol/L), and severely deficient (≤ 5 nmol/L). RESULTS: A total of 293 patients were included (52 eSE, 40 ICU-noSE, 44 non-ICU, and 157 outpatient). The median age was 55 (range 19-99) years. The median PLP level of the eSE group (12 nmol/L) was lower than that of the ICU-noSE (22 nmol/L, p = 0.003), non-ICU (16 nmol/L, p = 0.05), and outpatient groups (36 nmol/L, p < 0.001). Patients with eSE had a significantly higher prevalence of marginal and deficient PLP levels (90 and 80%, respectively) than patients in each of the other three groups (ICU-noSE: 70, 50%; non-ICU: 63, 54%; outpatient: 38, 21%). This significantly higher prevalence persisted after correcting for critical illness severity and timing of PLP level collection. CONCLUSIONS: Our study confirms previous findings indicating a high prevalence of pyridoxine deficiency (as measured by serum PLP levels) in patients with eSE, including when using a more restricted definition of pyridoxine deficiency. Prevalence is higher in patients with eSE than in patients in all three control groups (ICU-noSE, non-ICU, and outpatient). Considering the role of pyridoxine, thus PLP, in the synthesis of γ-aminobutyric acid and its easy and safe administration, prospective studies on pyridoxine supplementation in patients with eSE are needed.

Integrative Genomics Identifies the Molecular Basis of Resistance to Azacitidine Therapy in Myelodysplastic Syndromes.

Myelodysplastic syndromes and chronic myelomonocytic leukemia are blood disorders characterized by ineffective hematopoiesis and progressive marrow failure that can transform into acute leukemia. The DNA methyltransferase inhibitor 5-azacytidine (AZA) is the most effective pharmacological option, but only ∼50% of patients respond. A response only manifests after many months of treatment and is transient. The reasons underlying AZA resistance are unknown, and few alternatives exist for non-responders. Here, we show that AZA responders have more hematopoietic progenitor cells (HPCs) in the cell cycle. Non-responder HPC quiescence is mediated by integrin α5 (ITGA5) signaling and their hematopoietic potential improved by combining AZA with an ITGA5 inhibitor. AZA response is associated with the induction of an inflammatory response in HPCs in vivo. By molecular bar coding and tracking individual clones, we found that, although AZA alters the sub-clonal contribution to different lineages, founder clones are not eliminated and continue to drive hematopoiesis even in complete responders.

Morphometric analysis of inflammation in bronchial biopsies following exposure to inhaled diesel exhaust and allergen challenge in atopic subjects.

BACKGROUND: Allergen exposure and air pollution are two risk factors for asthma development and airway inflammation that have been examined extensively in isolation. The impact of combined allergen and diesel exhaust exposure has received considerably less attention. Diesel exhaust (DE) is a major contributor to ambient particulate matter (PM) air pollution, which can act as an adjuvant to immune responses and augment allergic inflammation. We aimed to clarify whether DE increases allergen-induced inflammation and cellular immune response in the airways of atopic human subjects. METHODS: Twelve atopic subjects were exposed to DE 300 µg.m(-3) or filtered air for 2 h in a blinded crossover study design with a four-week washout period between arms. One hour following either filtered air or DE exposure, subjects were exposed to allergen or saline (vehicle control) via segmental challenge. Forty-eight hours post-allergen or control exposure, bronchial biopsies were collected. The study design generated 4 different conditions: filtered air + saline (FAS), DE + saline (DES), filtered air + allergen (FAA) and DE + allergen (DEA). Biopsies sections were immunostained for tryptase, eosinophil cationic protein (ECP), neutrophil elastase (NE), CD138, CD4 and interleukin (IL)-4. The percent positivity of positive cells were quantified in the bronchial submucosa. RESULTS: The percent positivity for tryptase expression and ECP expression remained unchanged in the bronchial submucosa in all conditions. CD4 % positive staining in DEA (0.311 ± 0.060) was elevated relative to FAS (0.087 ± 0.018; p = 0.035). IL-4% positive staining in DEA (0.548 ± 0.143) was elevated relative to FAS (0.127 ± 0.062; p = 0.034). CD138 % positive staining in DEA (0.120 ± 0.031) was elevated relative to FAS (0.017 ± 0.006; p = 0.015), DES (0.044 ± 0.024; p = 0.040), and FAA (0.044 ± 0.008; p = 0.037). CD138% positive staining in FAA (0.044 ± 0.008) was elevated relative to FAS (0.017 ± 0.006; p = 0.049). NE percent positive staining in DEA (0.224 ± 0.047) was elevated relative to FAS (0.045 ± 0.014; p = 0.031). CONCLUSIONS: In vivo allergen and DE co-exposure results in elevated CD4, IL-4, CD138 and NE in the respiratory submucosa of atopic subjects, while eosinophils and mast cells are not changed. TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01792232.

Effects of nutrient and lime additions in mine site rehabilitation strategies on the accumulation of antimony and arsenic by native Australian plants.

The effects of nutrient and lime additions on antimony (Sb) and arsenic (As) accumulation by native Australian and naturalised plants growing in two contaminated mine site soils (2,735 mg kg(-1) and 4,517 mg kg(-1) Sb; 826 mg kg(-1) and 1606 As mgkg(-1)) was investigated using a glasshouse pot experiment. The results indicated an increase in soil solution concentrations with nutrient addition in both soils and also with nutrient+lime addition for Sb in one soil. Metalloid concentrations in plant roots were significantly greater than concentrations in above ground plant parts. The metalloid transfer to above ground plant parts from the roots and from the soil was, however, low (ratio of leaf concentration/soil concentration≪1) for all species studied. Eucalyptus michaeliana was the most successful at colonisation with lowest metalloid transfer to above ground plant parts. Addition of nutrients and nutrients+lime to soils, in general, increased plant metalloid accumulation. Relative As accumulation was greater than that of Sb. All the plant species studied were suitable for consideration in the mine soil phytostabilisation strategies but lime additions should be limited and longer term trials also recommended.

Nutritional status and socio-ecological factors associated with overweight/obesity at a rural-serving US-Mexico border university.

INTRODUCTION: Globesity (the global epidemic of obesity), like undernutrition at the opposite end of the malnutrition spectrum, affects virtually all age and socioeconomic groups in developed and developing countries. Genetics, comorbid diseases and lifestyle factors have been associated with obesity and weight gain for college students. Little is known about obesity and lifestyle factors of campus students and employees located in rural areas. The purpose of this study was to examine the prevalence of overweight/obesity and socioecological elements of the obesogenic environment at a rural-serving US-Mexico border university. METHODS: Data were collected using a cross-sectional, convenience sample by anasynchronous electronic survey submitted to approximately 23 000 students, faculty and staff on the main campus of New Mexico State University. Self-reported anthropometric indicators were used as proxy measures of nutritional status. Factors analyzed include the prevalence overweight/obesity from calculated body mass index (BMI) and self-identified body image in the contexts of sex, age, ethnicity, role at the university (student or employee) and residence. Body mass index categories were analyzed for associations with reported prevalence of stress indicators such as clinically diagnosed anxiety or depression, and major diseases such as diabetes, hypertension, heart disease, cancer and stroke. RESULTS: A total of 3962 completed surveys were analyzed. Self-reported respondent rates (n = 3962) of overweight and obese individuals (47.2%) were less than those reported for the state (60.7%) in a 2010 national survey. When BMI was analyzed by sex, there was a significant difference (p = 0.003) between males and females. More males were overweight and obese than females. When BMI and BMI categories were assessed by age, ethnicity, role at the university and residence, each variable was found to have statistically significant differences. CONCLUSION: No one demographic or socioecological factor appears to have a predominant role in predicting obesity in the participants studied at this rural-serving university. The authors conclude that levels of overweight and obesity are multifactorial and should be addressed with more holistic actions. These findings suggest that future studies should look more closely at stressors in the environment as well as culturally acceptable versus ideal notions of weight and corpulence. Study findings also suggest that early intervention will be critical to reducing levels of overweight/obesity and associated complications as the population ages. Finally, this study provides evidence for health educators and policy makers to go beyond exercise and calories in/out to develop educational materials that can cross many barriers of culture, age, ethnicity, educational level, residence and body image.

Salmon consumption by pregnant women reduces ex vivo umbilical cord endothelial cell activation.

BACKGROUND: In vitro exposure of endothelial cells (ECs) to n-3 (omega-3) long-chain PUFAs (LCPUFAs) reduces cell adhesion molecule (CAM) expression. However, to our knowledge, no previous human studies have examined the influence of an altered diet on CAM expression. OBJECTIVE: We assessed whether salmon (rich in n-3 LCPUFAs) consumption twice a week during pregnancy affected offspring umbilical vein EC CAM expression. DESIGN: Women were randomly assigned to maintain their habitual diets or to consume 2 portions of salmon per week during pregnancy months 4-9. ECs were isolated from umbilical cord veins collected at birth and cultured. The cell surface expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) was assessed by flow cytometry after the culture of ECs in the presence and absence of bacterial LPS for 24 h. Cytokine and growth factor concentrations in culture supernatant fluid were measured by using a multiplex assay. RESULTS: LPS increased the expression of VCAM-1 and the production of several cytokines and growth factors. The level of ICAM-1 expression per cell [ie, the median fluorescence intensity (MFI)] was increased by LPS stimulation in the control group (16.9 ± 2.4 compared with 135.3 ± 20.2; P < 0.001) and to a lesser extent in the salmon group (14.1 ± 3.8 compared with 65.8 ± 22.4; P = 0.037). The ICAM-1 MFI in the salmon group after LPS stimulation was lower than in the control group (P = 0.006). CONCLUSION: Increased dietary salmon intake in pregnancy dampens offspring EC activation, which implicates a role for n-3 LCPUFAs in the suppression of inflammatory processes in humans. This trial was registered at clinicaltrials.gov as NCT00801502.

Chronic preclinical safety evaluation of Hematide, a pegylated peptidic erythropoiesis stimulating agent in monkeys.

Hematide is a synthetic peptide-based, pegylated erythropoiesis stimulating agent in clinical development for treatment of anemia. To support chronic clinical dosing requirements, a 9-month repeat dose IV monkey safety study was undertaken. Animals received 0, 0.2, 2 or 20 mg/kg hematide IV every three weeks for nine months followed by a 14-week recovery. Hematide administration was associated with time and dose-dependent polycythemia. Histological findings were related to exaggerated pharmacology that was secondary to the administration of an erythropoiesis stimulating agent to a normocythemic animal. In conclusion, these results support the use of repeated administration of hematide for the correction of anemia.

Preclinical safety and pharmacology of Hematide, a peptidic erythropoiesis stimulating agent (ESA), in rats and monkeys.

The pharmacology, toxicokinetics, and safety of Hematide, a synthetic peptidic erythropoiesis-stimulating agent (ESA), were characterized. Hematide was given intravenously (0, 0.5, 5, and 50 mg/kg) weekly for five weeks with a 6- (rat) and 12-week (monkey) recovery period. The pharmacological action of Hematide resulted in polycythemia. Histopathology consistent with drug-induced exaggerated pharmacology was observed primarily in rats. Secondary sequelae resulting from pronounced polycythemia was considered the cause of deaths in rats and a single high-dose monkey. Toxicokinetic analysis indicated prolonged exposure. In conclusion, Hematide is a potent ESA and the safety and efficacy profile support clinical development.