Nanocrocin Protective Effects on Paraquat-Induced Oxidative Stress in the MRC-5 Cell Line.

Paraquat (PQ) herbicide poisoning is a severe medical problem in developing countries without suitable therapy. This study aimed to investigate the effects of crocin (CCN) and nano crocin (NCCN) on PQ -induced toxicity in the MRC-5 cell line. The results showed that the particle size of NCCN was 140.3 ± 18.0 nm, and the zeta potential of the optimal crocin-loaded niosomes was 23.4 ± 2.8 mV. The NCCN was more effective than CCN in the inhibition of PQ-induced toxicity. Treatment of the MRC-5 cells leads to a decrease in ROS and an increase in SOD, CAT, GPX, and TAC levels in PQ-CCN and PQ-NCCN groups compared with the PQ group. These changes tended to be positively associated with the NCCN compared to CCN. Overall, NCCN was more effective than crocin in treating PQ-induced toxicity in vitro and deserved further preclinical consideration.

Protective Effects of Xanthine Derivatives Against Arsenic Trioxide-Induced Oxidative Stress in Mouse Hepatic and Renal Tissues.

In this study, the protective efficacy of pentoxifylline (PTX) as a xanthine derivative against arsenic trioxide (ATO)-induced kidney and liver damage in mice was investigated. Thirty-six mice were divided into six groups, receiving intraperitoneal injections of saline, ATO, PTX, or a combination for four weeks. Blood samples were analyzed for serum biochemistry, while hepatic tissue underwent examination for histopathological changes and assessment of oxidative stress markers and antioxidant gene expression through Real-Time PCR. ATO exposure significantly increased serum markers (creatinine, ALT, BUN, ALP, AST) and induced histopathological changes in the liver. Moreover, it elevated renal and hepatic nitric oxide (NO) and lipid peroxidation (LPO) levels, and reduced antioxidant enzyme expression (CAT, GSR, GPx, MPO, SOD), total thiol groups (TTGs), and total antioxidant capacity (TAC). Conversely, PTX treatment effectively lowered serum hepatic and renal markers, improved antioxidant markers, and induced histopathological alterations. Notably, PTX did not significantly affect renal and hepatic NO levels. These findings suggest that PTX offers therapeutic potential in mitigating liver and acute kidney injuries induced by various insults, including exposure to ATO.

Efficacy of a standardized herbal product from Pistacia atlantica subsp. Kurdica in type 2 diabetic patients with hyperlipidemia: A triple-blind randomized clinical trial.

BACKGROUND: Hyperlipidemia is one of the consequences of type 2 diabetes mellitus (T2DM) that puts the patients at the risk of getting cardiovascular disease. Pistacia atlantica subsp. Kurdica is used by local people for the improvement of lipid and glucose indices. This study was carried out to evaluate clinical effects of P. atlantica subsp. Kurdica on hyperlipidemia related to T2DM patients. MATERIALS AND METHODS: In this randomized, triple-blind, and placebo-controlled study, type 2 diabetes patients with hyperlipidemia were randomly allocated to receive either P. atlantica kurdica or placebo capsule for 2 months. 58 Patients were followed up at the beginning and after the end of each month for assessment of lipid profiles, glucose indices, and liver and renal function tests. The herbal capsule was standardized according to volatile and nonvolatile compounds by GC-MS/FID and RP-HPLC-PDA, respectively. The total phenolic and flavonoid contents were also determined with a spectrophotometer. RESULTS: After 1 and 2 months of the intervention period, mean differences of 2HPP, total cholesterol, and LDL-c have been reduced significantly (P < 0.05) between the two groups, but there were not reported any significant statistical changes in FBS, HbA1c, TG, HDL-c, ALT, AST, and Cr. The herbal capsule was standardized according to benzoic acid, ballic acid, rutin, and quercetin standard (6.5, 2.1, 1.4, 0.7 mg, respectively), and also α-pinene as major volatile constituent 28.51%. CONCLUSION: According to results the P. atlantica kurdica is effective in the improvement of lipid profile and glucose indices in line with its local application. CLINICAL TRIAL ID: (IRCT201708109014N178).

Clinician perspectives on the need for training on caring for pregnant women with intellectual and developmental disabilities.

BACKGROUND: Women with intellectual and developmental disabilities (IDDs) experience disparities in obstetric care access and quality, in addition to communication gaps with healthcare providers. Many obstetric providers are untrained and uneducated about critical aspects of providing care to persons with IDDs. OBJECTIVE: The study was conducted to describe obstetric clinicians' training experiences related to providing obstetric care to women with IDDs, to assess the perceived need for formalized training, and to identify recommendations for training content. METHODS: This study involved qualitative individual interviews (n = 9) and one focus group (n = 8) with obstetric clinicians who self-reported experience caring for women with IDDs during pregnancy. Descriptive coding and content analysis techniques were used to develop an iterative codebook related to education and training; codes were applied to the data. Coded data were analyzed for larger themes and relationships. RESULTS: Analysis revealed three main themes: 1. Need for obstetric training and education: No participant reported receiving any training in caring for pregnant women with IDDs. Participants expressed a need for formal education. 2. Recommendations for formal training: Participants noted the need for training during residency and beyond, and all healthcare staff members should be included in training. 3. Training outcomes should increase knowledge, enhance attitudes, and develop practical skills related to care for pregnant women with IDDs. CONCLUSION: Results indicate a need for systematic training efforts regarding obstetric care for women with IDDs. Improved training and education may decrease health inequities and improve the quality of care, and thus pregnancy outcomes, for women with IDDs. LEVEL OF EVIDENCE: VI.

Complications following hysterectomy in women with intellectual and developmental disabilities.

BACKGROUND: Limited data exist on complications following hysterectomy among women with intellectual and developmental disabilities (IDD). OBJECTIVE: The objective was to assess the frequencies of postoperative complications in women with IDD following hysterectomy. METHODS: The National Inpatient Sample from 2014 to 2017 was queried using codes from the International Classification of Disease 9th and 10th revisions to identify women over 15 years of age with a diagnosis of an IDD undergoing hysterectomy. Comparisons were made to women without IDD undergoing the same procedure. Logistic regression analysis was performed to examine between group differences in the frequency of clinical post-surgical complications while adjusting for potential confounding variables. RESULTS: Of eligible women undergoing hysterectomy, 1,370 were identified as having IDD and 624,700 did not. Compared to controls, women with IDD were significantly younger (45 vs. 50 years, p < 0.001). Women with IDD were also more likely to have had governmental health insurance (83% vs. 34%, p < 0.001), an open hysterectomy approach (78% vs. 69%, p = 0.002), and longer hospital stays (4 vs. 3 days, p < 0.001). After adjusting for potential confounders, women with IDD had greater odds of postoperative urinary complications (OR 3.74, 95% CI 1.18-11.83) and complications related to decubitus ulcer formation (OR 8.97, 95% CI 2.10-38.36). CONCLUSIONS: Women with IDD have increased odds having urinary and decubitus ulcer complications following hysterectomy, compared to women without IDD. These results inform surgical decision-making and anticipatory guidance for these women and their caregivers.

PAPPA-mediated adipose tissue remodeling mitigates insulin resistance and protects against gestational diabetes in mice and humans.

Pregnancy is a physiological state of continuous adaptation to changing maternal and fetal nutritional needs, including a reduction of maternal insulin sensitivity allowing for appropriately enhanced glucose availability to the fetus. However, excessive insulin resistance in conjunction with insufficient insulin secretion results in gestational diabetes mellitus (GDM), greatly increasing the risk for pregnancy complications and predisposing both mothers and offspring to future metabolic disease. Here, we report a signaling pathway connecting pregnancy-associated plasma protein A (PAPPA) with adipose tissue expansion in pregnancy. Adipose tissue plays a central role in the regulation of insulin sensitivity, and we show that, in both mice and humans, pregnancy caused remodeling of adipose tissue evidenced by altered adipocyte size, vascularization, and in vitro expansion capacity. PAPPA is known to be a metalloprotease secreted by human placenta that modulates insulin-like growth factor (IGF) bioavailability through prolteolysis of IGF binding proteins (IGFBPs) 2, 4, and 5. We demonstrate that recombinant PAPPA can stimulate ex vivo human adipose tissue expansion in an IGFBP-5- and IGF-1-dependent manner. Moreover, mice lacking PAPPA displayed impaired adipose tissue remodeling, pregnancy-induced insulin resistance, and hepatic steatosis, recapitulating multiple aspects of human GDM. In a cohort of 6361 pregnant women, concentrations of circulating PAPPA are inversely correlated with glycemia and odds of developing GDM. These data identify PAPPA and the IGF signaling pathway as necessary for the regulation of maternal adipose tissue physiology and systemic glucose homeostasis, with consequences for long-term metabolic risk and potential for therapeutic use.

Upper Gastrointestinal Perforations: A Possible Danger of Antibiotic Overuse.

BACKGROUND: The role of changes in gut microflora on upper gastrointestinal (UGI) perforations is not known. We conducted a retrospective case-control study to examine the relationship between antibiotic exposure-a proxy for microbiome modulation-and UGI perforations in a national sample. METHODS: We queried a 5% random sample of Medicare (2009-2013) to identify patients ≥ 65 years old hospitalized with UGI (stomach or small intestine) perforations using International Classification of Diseases diagnosis codes. Cases with UGI perforations were matched with 4 controls, each based on age and sex. Exposure to outpatient antibiotics (0-30, 31-60, 61-90 days) prior to case patients' index hospitalization admission data was determined with Part D claims. Univariate and multivariable regression analyses were performed to evaluate the effect of antibiotic exposure on UGI perforation. RESULTS: Overall, 504 cases and 2016 matched controls were identified. Compared to controls, more cases had antibiotic exposure 0-30 days (19% vs. 3%, p < 0.001) and 31-60 days (5% vs. 2%, p < 0.001) prior to admission. In adjusted analyses, antibiotic exposure 0-30 days prior to admission was associated with 6.8 increased odds of an UGI perforation (95% CI 4.8, 9.8); 31-60 days was associated with 1.9 increased odds (95% CI 1.1, 3.3); and 61-90 days was associated with 3.7 increased odds (95% CI 2.0, 6.9). CONCLUSIONS: Recent outpatient antibiotic use, in particular in the preceding 30 days, is associated with UGI perforation among Medicare beneficiaries. Exposure to antibiotics, one of the most modifiable determinants of the microbiome, should be minimized in the outpatient setting.

A Systematic Review of Development Programs Designed to Address Leadership in Academic Health Center Faculty.

INTRODUCTION: To describe Academic Health Center (AHC) faculty leadership development program characteristics and categorize leadership topics into thematic areas suggesting competency domains to guide programmatic curricular development. METHODS: A systematic literature review was conducted (PubMed/MEDLINE, Scopus, Cumulative Index of Nursing and Allied Health Literature [CINAHL], and Journal Storage [JSTOR databases]). Eligible studies described programs with leadership development intent for faculty in AHCs. Information was extracted using a structured data form and process. RESULTS: Six hundred ninety citations were screened; 25 publications describing 22 unique programs were eligible. The majority (73%) were institutionally based; mean class size was 18.5 (SD ± 10.2, range 4.5-48); and mean in-person time commitment was 110 hours (SD ± 101.2, range 16-416), commonly occurring in regular intervals over months to years (n = 10, 45%). Six programs provided per participant costs (mean $7,400, range $1000-$21,000). Didactic teaching was the primary instructional method (99.5%); a majority (68%) included project work. Fourteen thematic content areas were derived from 264 abstracted topics. The majority or near majority incorporated content regarding leadership skills, organizational strategy and alignment, management, self-assessment, and finance/budget. DISCUSSION: Institutions and faculty invest significantly in leadership development programs, addressing perceived needs and with perceived benefit for both. The prevalence of common curricular content indicates that AHCs deem important faculty development in leadership, business, and self-assessment skills.

Attempted and Successful Vacuum-Assisted Vaginal Delivery by Prepregnancy Body Mass Index.

OBJECTIVE: To examine rates of attempted and successful vacuum-assisted vaginal delivery by prepregnancy body mass index (BMI). METHODS: We conducted a retrospective cohort study of 2,084 women with singleton gestations needing operative delivery assistance and vacuum-eligible (fully dilated, +2 station or greater, 34 weeks of gestation or greater) using 2006-2014 inpatient records. Prepregnancy BMI was categorized as underweight (less than 18.5), normal weight (18.5 to less than 25), overweight (25 to less than 30), or obese (30 or greater). Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) of attempted and successful vacuum-assisted vaginal delivery by prepregnancy BMI adjusted for age, race, marital status, parity, diabetes, labor induction-augmentation, episiotomy, gestational age, and neonatal birth weight. RESULTS: Thirty-nine percent of women requiring delivery assistance and eligible for a vacuum were overweight or obese, 79% had vacuum attempts, and 95.3% of attempted vacuum-assisted vaginal deliveries were successful. Compared with women who were normal weight prepregnancy (82.8%), women who were overweight or obese were less likely to have vacuum attempted (75.8%, OR 0.71, 95% CI 0.53-0.96 and 71.2%, OR 0.53, 95% CI 0.39-0.74, respectively). Among women with attempted vacuum-assisted vaginal delivery, successful delivery did not differ by prepregnancy BMI (92.6%, OR 0.54, 95% CI 0.21-1.37 for underweight; 94.5%, OR 1.07, 95% CI 0.57-2.00 for overweight; 96.3%, OR 1.09, 95% CI 0.51-2.33 for obese compared with 95.6% among normal-weight women). CONCLUSION: Among women in need of operative delivery assistance, prepregnancy obesity was associated with lower likelihood of attempted vacuum-assisted vaginal delivery but, if attempted, success rates were similar to rates among normal-weight women. With significant morbidity of second-stage cesarean delivery in obese women, research should examine whether vacuum-assisted vaginal delivery may be appropriate for additional obese patients.

Anticoagulant activity of isolated coumarins (suberosin and suberenol) and toxicity evaluation of Ferulago carduchorum in rats.

CONTEXT: Ferulago carduchorum Boiss. & Hausskn. (Apiaceae) is known as Chavil in Persian which grows in west of Iran. Local people add Chavil to dairy and oil ghee as a natural preservative to extend the expiration date. OBJECTIVE: The goal of this survey is the safety evaluation of the total extract of F. carduchorum in rats by determining both oral acute and subchronic toxicities; furthermore, the anticoagulant activity of isolated coumarins was evaluated. MATERIALS AND METHODS: The aerial parts of F. carduchorum were extracted by the percolation method. The anticoagulant activity of isolated coumarins was evaluated and the total extract was used to investigate acute and subchronic toxicity in rats. In the subchronic toxicity model, doses of 250, 500, and 1000 mg/kg of the extract were administered to treated groups for 30 consecutive days by gavage. RESULTS: According to the results of acute toxicity, the LD50 of Chavil extract was more than 2000 mg/kg. The subchronic study showed no significant difference (p > 0.05) between the groups treated with extract and control groups in hematological (erythrocyte, total and differential leukocyte, hematocrit, hemoglobin, platelet count) and biochemical parameter (glucose, albumin, cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) evaluations. The isolated coumarins (suberosin and suberenol) prolonged the prothrombin time (PT) at doses of 3 and 6 mg/kg compared with control (p < 0.05). The longest PT was for suberosin at 6 mg/kg (17.4 s). CONCLUSION: In conclusion, oral administration of the Chavil extract did not cause either acute or subchronic toxicities although the coumarins showed anticoagulant effect in rats.