Association of vitamin D deficiency and vitamin D receptor (VDR) gene single-nucleotide polymorphism (rs7975232) with risk of preeclampsia.

BACKGROUND: Preeclampsia has a multifactorial-yet-elusive etiology. Recent reports suggest a link between preeclampsia and vitamin D (VD) metabolic axis. Genetic variations like single-nucleotide polymorphisms (SNPs) of vitamin D receptor (VDR) gene can alter the metabolic role of VD, which have been shown by several genetic association studies. However, there is discordance among these studies. OBJECTIVE: The current study aimed to investigate the association of VDR gene polymorphism (ApaI) and VD deficiency with risk of developing preeclampsia. PATIENTS AND METHOD: In this case-control study, 40 preeclamptic and 40 normotensive pregnant women were compared for VD status and VDR gene polymorphism. Serum 25-hydroxyvitamin-D [25(OH) D] level was determined by enzyme-linked immunosorbent assay (ELISA) and VDR gene polymorphism Apa1 was analyzed by Allele specific polymerase chain reaction (AS-PCR) using sequence specific primers. RESULTS: Serum levels of 25(OH) D were very low but comparable in both preeclamptic and normotensive pregnant women. The difference between the two groups were not statistically significant (p = .423). VDR gene polymorphism ApaI (rs7975232) was found not to have significant association with the risk of developing preeclampsia. The frequencies of wild genotype (GG) in preeclamptic and normotensive women were 27.5% and 22.5% respectively. A total of 25% of preeclamptic women had mutant homozygous genotype (TT) and 17.5% of normotensive women had mutant homozygous genotype. The frequency of mutant heterozygous genotype (GT) in preeclamptic patients was 47.5% and in normotensive women was 60%. The variation of wild and mutant genotypes between the two groups was not statistically significant (p > .05). CONCLUSION: This study showed that VDR gene polymorphism (ApaI) and VD deficiency are not associated with the risk of preeclampsia.

Effects of different progesterone levels on reproductive outcomes in assisted reproductive technologies: from molecular basis to treatment strategies.

PURPOSE: The aim of this narrative review is to offer an overview about the role of progesterone levels on pregnancy outcome in patients undergoing assisted reproductive technologies (ARTs). METHODS: A detailed computerized search of the literature was performed in the main electronic databases (MEDLINE, EMBASE, Web of Science) to determine the importance of elevated progesterone levels at different stages of the cycle for pregnancy rates in the in vitro fertilization (IVF) cycle. Our review also provides information on the differences between elevated progesterone levels and their interpretation in normal and in poorly responding women. RESULTS: After careful evaluation, our search strategy yielded a total of 15 included articles, showing the possible factors that may have had an impact on the increased progesterone level before human chorionic gonadotropin (HCG) injection and the different thresholds above which the pregnancy rate was lower. Furthermore, increased progesterone on cycle day 2 or 3 could serve as a marker for increased progesterone in the late follicular phase, which is associated with a lower pregnancy rate. CONCLUSION: Despite the literature data that support the negative effect of elevated progesterone on fresh cycles, due to lack of randomized controlled trials, the value of measuring progesterone in daily practice is questionable. Available evidence supports the detrimental effect of elevated progesterone in different subgroups of women, although there is still the need for defining different thresholds and durations of high progesterone exposure. The need for various thresholds for different cohorts of women, the inter-assay variability is making this decision harder.

The short-term impact of high energy nutritional supplements on energy balance in underweight primi-gravidae: A randomized controlled trial.

OBJECTIVE: To determine the impact of high-energy nutritional supplements on appetite, appetite regulators, energy intake and macronutrients level among underweight primigravidae. Methods: The single-blind randomised controlled trial was conducted from April 26, 2018, to August 10, 2019, in tertiary care hospitals of Khyber Pakhtunkhwa province of Pakistan, after approval from the ethics review committee of Khyber Medical University, Peshawar, and comprised underweight primigravidae who were randomly allocated to high energy nutritional supplement group A and placebo group B. Appetite questionnaires were filled and blood samples were obtained in fasting state, at 30, 60, 120, 210 and 270 minutes to measure blood glucose, insulin, peptide YY and cholecystokinin. Breakfast and lunch were served at 30 minutes and 210 minutes after supplementation, respectively. Data was analysed using SPSS 20. RESULTS: Of the 36 subjects, 19(52.8%) were in group A and 17(47.2%) were in group B. The overall mean age was 18.66 ± 2.5 years. Energy intake in group A was significantly higher than group B (p<0.001), and so were mean protein and fats (p<0.001). The subjective appetite perceptions for 'hunger' and 'desire to eat' were significantly lower (p<0.001) before lunch in group A. Plasma concentrations of appetite hormones corresponded to the appetite perceptions and were significantly higher in group A after breakfast and lunch for peptide YY, cholecystokinin and insulin compared to group B (p<0.001). CONCLUSIONS: High-energy nutritional supplement was found to have short-term suppressive effect on energy intake and appetite. Trial registration: ClinicalTrials.gov Identifier: ISRCTN 10088578. Registered on 27 March 2018. https://www.isrctn.com/ ISRCTN10088578.

Temporal Trends in Internal vs. External Referrals for TAVR in a Large Academic Center: Patients Characteristics and Outcomes.

Background: Since transcatheter aortic valve replacement (TAVR) first became approved for inoperable patients followed by high, intermediate-, and low-risk patients, referrals to TAVR centers have rapidly increased. The purpose of this study was to investigate referral patterns to a large academic TAVR center in the state of North Carolina and evaluate differences between externally and internally referred patients. Methods: Data for all patients who underwent TAVR at our institution between November 2014 and March 2020 were pulled from the Transcatheter Valve Therapy Registry. The electronic medical record was used to determine the referral source. The descriptive statistical analysis was performed using Excel (Microsoft, Redmond, Washington). Results: 491 patients underwent TAVR at our institution between November 2014 and March 2020. Half of the patients were referred by a cardiologist within the same health system (N = 250, 50.9%). Other referral sources included a cardiologist external to the health system (N = 210, N = 42.8%) and a surgeon or proceduralist (such as urologist, surgeon, or gastroenterologist) during the workup for another procedure (N = 26, 5.3%). Over time, there was a trend toward an increasing proportion of patients referred by a cardiologist external to our system, but this trend did not reach statistical significance (20.0% in 2014, 29.2% in 2015, 30.7% in 2016, 53.0% in 2017, 36% in 2018, 48.4% in 2019, and 56.8% in 2020, p=0.06 using the Mann-Kendall trend test). Externally referred patients were less likely to have private insurance and were more likely to have a reduced ejection fraction and had a higher mean gradient across the valve. Postprocedure, externally referred patients were more likely to have the procedure under moderate sedation and less likely to be discharged home. Conclusions: This study presents the referral pattern to a large TAVR center in North Carolina. Over time, there was an increase in external referrals suggesting that TAVR is increasingly adopted as an important component of the management of aortic valve stenosis. Internally and externally referred patients have differences in baseline demographic and clinical characteristics which may have an impact on clinical outcomes.

Very high PD-L1 expression as a prognostic indicator of overall survival among patients with advanced non-small cell lung cancer receiving anti-PD-(L)1 monotherapies in routine practice.

PURPOSE: Programmed death or ligand-1 (PD-(L)1) pathway inhibitors confer improved survival as the first-line treatment for advanced non-small cell lung cancer (aNSCLC) in patients with PD-L1 expression (PD-L1 + e ≥ 50%) compared to platinum-doublet chemotherapy and have become a standard therapy. Some recent evidence suggests that among aNSCLC patients with PD-L1 + e of ≥50% receiving pembrolizumab monotherapy, very high levels of PD-L1 + e (≥90%) may be associated with better outcomes. We sought to assess whether very high PD-L1 + e (≥90%) compared to high PD-L1 + e (50%-89%) is associated with an overall survival benefit in aNSCLC patients receiving anti-PD-(L)1 monotherapies. METHODS: We conducted a single-site retrospective cohort study of aNSCLC patients who initiated PD-(L)1 inhibitor monotherapy as the first-line treatment from October 24, 2016, to August 25, 2021, and had a PD-L1 + e ≥ 50%. The primary outcome was overall survival, measured from the start of the first-line PD-(L)1 inhibitor monotherapy (index date) to date of death or last confirmed activity prior to the cohort exit date. Propensity score-based inverse probability weighting (IPW) was used to control for confounding in Kaplan-Meier curves and Cox proportional hazard regression analysis. RESULTS: One hundred sixty-six patients with aNSCLC receiving PD-(L)1 inhibitor monotherapy met inclusion criteria. 54% were female, 90% received pembrolizumab, median age was 68 years, 70% had non-squamous cell carcinoma, 94% had a history of smoking, 29% had a KRAS mutation, and 37% had very high PD-L1 + e. Unweighted covariates at cohort entry were similar between groups (absolute standardized mean differences [SMDs] <0.1) except for race (SMD = 0.2); age at therapy initiation (SMD = 0.13); smoking status (SMD = 0.13), and BRAF mutation status (SMD = 0.11). After weighting, baseline covariates were well balanced (all absolute SMDs <0.1). In the weighted analysis, having a very high PD-L1 + e was associated with lower mortality (weighted hazard ratio 0.57, 95% CI 0.36-0.90) and longer median survival: 3.85 versus 1.49 years. CONCLUSIONS: Very high PD-L1 + e (≥90%) was associated with an overall survival benefit over high PD-L1 + e (50%-89%) in patients receiving the first-line PD-(L)1 inhibitor monotherapy in a model controlling for potential confounders. These findings should be confirmed in a larger real-world data set.

QoS-Aware Cost Minimization Strategy for AMI Applications in Smart Grid Using Cloud Computing.

Cloud computing coupled with Internet of Things technology provides a wide range of cloud services such as memory, storage, computational processing, network bandwidth, and database application to the end users on demand over the Internet. More specifically, cloud computing provides efficient services such as "pay as per usage". However, Utility providers in Smart Grid are facing challenges in the design and implementation of such architecture in order to minimize the cost of underlying hardware, software, and network services. In Smart Grid, smart meters generate a large volume of different traffics, due to which efficient utilization of available resources such as buffer, storage, limited processing, and bandwidth is required in a cost-effective manner in the underlying network infrastructure. In such context, this article introduces a QoS-aware Hybrid Queue Scheduling (HQS) model that can be seen over the IoT-based network integrated with cloud environment for different advanced metering infrastructure (AMI) application traffic, which have different QoS levels in the Smart Grid network. The proposed optimization model supports, classifies, and prioritizes the AMI application traffic. The main objective is to reduce the cost of buffer, processing power, and network bandwidth utilized by AMI applications in the cloud environment. For this, we developed a simulation model in the CloudSim simulator that uses a simple mathematical model in order to achieve the objective function. During the simulations, the effects of various numbers of cloudlets on the cost of virtual machine resources such as RAM, CPU processing, and available bandwidth have been investigated in cloud computing. The obtained simulation results exhibited that our proposed model successfully competes with the previous schemes in terms of minimizing the processing, memory, and bandwidth cost by a significant margin. Moreover, the simulation results confirmed that the proposed optimization model behaves as expected and is realistic for AMI application traffic in the Smart Grid network using cloud computing.

Adverse Events of Novel Therapies for Hematologic Malignancies: What Emergency Physicians Should Know.

In the past decade, rapid advances in therapeutic target discovery in hematologic malignancies have led to many clinical studies demonstrating efficacy of novel agents. Between 2014 and 2018, Food and Drug Administration approvals of new drugs and agents have increased, with greater than 2 dozen novel agents. Rapidly identifying the risk profiles of these cancer therapeutics that may present with acute toxicities and understanding the timing, sequence, duration, and treatment of disease processes are the most important challenges faced by practitioners in emergency medicine, even in nononcologic centers. The emergency medicine literature lags behind rapid advances in oncology, and guidelines for rapid recognition and management of these emerging entities are not familiar. In this Review Article, we discuss the most recent and clinically relevant developments in the arena of hematologic malignancies, further expanding on drug toxicities and their clinical presentations and offering suggestions for management. Specifically, we discuss immune-related adverse events after immune checkpoint inhibitor therapy (including myocarditis and hemophagocytic lymphohistiocytosis), chimeric antigen receptor-T cell therapy, cytokine release syndrome, chimeric antigen receptor-T cell-related encephalopathy syndrome, differentiation syndrome, sinusoid occlusion syndrome, QT-interval prolongation, and tumor lysis syndrome. Rapid advances in hematology and oncology will bring many new challenges for emergency health care providers in the near future; thus, the urgency to raise awareness among this community.

Unpasteurised milk consumption as a potential risk factor for toxoplasmosis in females with recurrent pregnancy loss.

In women with a bad obstetric history, certain infections are associated with recurrent foetal loss. One of the common infectious agents is a protozoan parasite, Toxoplasma gondii. The aim of this study was to assess unpasteurised milk consumption as a potential risk factor for toxoplasmosis in females with recurrent pregnancy loss from the province of Khyber Pakhtunkhwa, Pakistan. In this study, we recruited a total of 360 females, comprising a study group of 180 females with previous history of recurrent pregnancy loss and a control group of 180 females with no such history. Blood serum from the participants was analysed for Toxoplasma gondii IgM antibodies by enzyme linked immunosorbent assay. Among the study group, 23 (12.8%) females were serologically positive for IgM antibodies against Toxoplasma gondii, whilst 157 (87.2%) were IgM negative. In the control group, only two (4.8%) females were IgM positive, whilst 178 (95.2%) were IgM negative. Bad pregnancy outcome in the study group and control group was observed to be significantly different (p < .0001). In both of these groups, unpasteurised milk consumption was found as a major risk factor for Toxoplasma gondii infection. A routine serological investigation should be carried out in pregnant women to rule out toxoplasmosis and reduce the risk of recurrent pregnancy loss as well as congenital toxoplasmosis in newborns.Impact statementWhat is already known on this subject? Seropositivity for Toxoplasma gondii antibodies ranges from 7% to 51% in different regions of the world. The prevalence rate varies because of differences in climate, culture, food habits, behaviour, personal hygiene and cooking habits of different societies and ethnic groups. Various risk factors have been identified that contribute to a high prevalence rate of the disease, including consumption of raw or poorly cooked meat, physical contact with cats or cat litter, consumption of unwashed raw vegetables and fruits, drinking of contaminated water and milk. We presumed that consuming unpasteurised milk could be a potential risk factor for developing toxoplasmosis in pregnant women.What the results of this study add? This study demonstrates high seroprevalence of Toxoplasma gondii antibodies in females of child bearing age that have consumed unpasteurised milk and is a potential risk factor for developing toxoplasmosis.What the implications are of these findings for clinical practice and/or further research? Our findings suggest that primary preventive measures (personal hygiene, frequent hand washing and consuming pasteurised milk) should be taken by health surveillance authorities to focus on families, especially pregnant women, to educate them about personal hygiene, contact with cattle or using their milk and milk products. The latter is especially important to aware them about the hazards of consuming unpasteurised and contaminated milk.

Treatment with Metformin and Combination of Metformin Plus Pioglitazone on Serum Levels of IL-6 and IL-8 in Polycystic Ovary Syndrome: A Randomized Clinical Trial.

Elevated serum levels of inflammatory mediators in conditions such as PCOS reflect a low-grade chronic inflammation and this has been attributed to be associated with insulin-resistance in PCOS. Therefore, insulin-sensitizing agents are suggested to improve both reproductive as well as metabolic aspects of PCOS. This study aimed to compare the effects of metformin taken alone with that of a combination of metformin and pioglitazone on menstrual cycle, hormonal parameters, insulin resistance, and inflammatory biomarkers in women with PCOS. One hundred and six women with PCOS participated in the study. All subjects were randomized into two-arm intervention groups (Arm 1 and 2). Participants in Arm-1 received metformin (500 mg BD) daily while those in Arm-2 a combination of metformin (500 mg BD) and pioglitazone (15 mg BD) for 12 wks. Serum levels of IL-6 and IL-8 were measured using ELISA whereas insulin resistance was assessed using HOMA-IR. At baseline women with PCOS had significantly elevated circulating concentrations of IL-6 and IL-8. Treatment decreased IL-6 in both the groups, however, only the combination group showed a significant decrease (p=0.005). Serum IL-8 level had a significant decrease after treatment in both groups (p <0.001). HOMA-IR and insulin levels also decreased in both the groups (both p <0.001). Testosterone, FSH, and prolactin significantly decreased in both groups. LH also decreased in both groups, however, the change was significant only in the combination group (p=0.013). Combination of metformin and pioglitazone therapy was more effective as compared to metformin alone in reducing the levels of IL-6 and IL-8 as well as insulin resistance in PCOS.

Use of Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Autoimmune Disease: A Systematic Review.

Background: Cancer immunotherapy with checkpoint inhibitors (CPIs) is associated with frequent immune-related adverse events (irAEs) and is often not recommended for patients with concomitant autoimmune disease. Purpose: To summarize the evidence on adverse events associated with CPIs in patients with cancer and preexisting autoimmune disease. Data Sources: MEDLINE, EMBASE, Web of Science, PubMed ePubs, and the Cochrane Central Register of Controlled Trials through September 2017 with no language restrictions. Study Selection: Original case reports, case series, and observational studies describing patients with cancer and autoimmune disease who were receiving CPIs. Data Extraction: 2 reviewers independently extracted data and assessed the quality of reporting. Data Synthesis: 123 patients in 49 publications were identified; 92 (75%) had exacerbation of preexisting autoimmune disease, irAEs, or both. No differences in adverse events were observed in patients with active versus inactive disease. Patients receiving immunosuppressive therapy at initiation of CPI therapy seemed to have fewer adverse events than those not receiving treatment. Most flares and irAEs were managed with corticosteroids; 16% required other immunosuppressive therapies. Adverse events improved in more than half of patients without discontinuation of CPI therapy. Three patients died of adverse events. Limitations: The quality and quantity of data were limited. Case reports typically describe unique manifestations and are not generalizable to the population at large. Because there were no prospective observational studies, incidence could not be determined. Conclusion: Flares and irAEs in patients with autoimmune disease who are receiving CPIs can often be managed without discontinuing therapy, although some events may be severe and fatal. Prospective longitudinal studies are needed to establish incidence of adverse events and evaluate risk-benefit ratios and patient preferences in this population. Primary Funding Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Correlation of plasma kisspeptin with total testosterone levels in smokeless tobacco and smoking tobacco users in a healthy cohort: A cross-sectional study.

Human infertility is a worldwide health issue and is the inability to conceive following twelve months of unprotected sexual intercourse. Consistent studies reiterated tobacco abuse to be an important risk factor which adversely effects male fertility. This study aims to determine the correlation of kisspeptin and total testosterone levels in smokeless tobacco, smoking tobacco users and healthy controls. A total of 180 subjects were selected using random sampling technique. Non-fasting blood samples (5 ml) were drawn, and ELISA technique was used for the evaluation of plasma levels of kisspeptin and total testosterone. Total testosterone was found to be significantly high in smokers and smokeless tobacco users, while the level of kisspeptin was found to be significantly high in smokeless tobacco users only as compared to control group. Furthermore, the level of cholesterol was found to be significantly low, whereas HDL and triglycerides were found to be significantly high in smokeless tobacco users relative to control subjects. Findings of this study suggest that tobacco use has impact on HPG axis by affecting kisspeptin level. The increase in kisspeptin level can affect hypothalamic function leading to pituitary and gonadal dysfunction along with impairment of reproduction. The finding that smokeless tobacco significantly raises kisspeptin strengthens the idea that smokeless tobacco use has more potent effects centrally compared to smoking.

Extramedullary Plasmacytoma Involving the Trachea: A Case Report and Literature Review.

BACKGROUND: Extramedullary plasmacytoma is an uncommon type of plasma cell neoplasm that occurs outside of the bone marrow. Very rarely, extramedullary plasmacytomas can involve the trachea, causing significant respiratory distress. CASE REPORT: We describe a patient with a history of multiple myeloma who presented with voice hoarseness and dyspnea and was found to have airway obstruction due to an extramedullary plasmacytoma near the larynx. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: It is important to investigate the possibility of upper airway obstruction in cancer patients presenting with hoarseness and dyspnea to prevent incorrect management, which can lead to fatal results. In particular, wheezing and dyspnea in patients with a history of asthma may not always be due to asthma exacerbation. Computed tomography scans and emergency laryngoscopy have been shown to be useful in aiding with correct diagnosis of upper airway obstruction, ensuring appropriate treatment.

Association of hypoadiponectemia with smokeless/dipping tobacco use in young men.

BACKGROUND: Low levels of adiponectin, an adipocytokine with anti-diabetic, antiatherogenic and cardioprotective properties, is associated with increased risk of coronary disease in young men. Previous studies have demonstrated that smokeless tobacco is linked with a reduction of plasma adiponectin levels. However, the influence of smokeless tobacco (dipping tobacco) on plasma adiponectin levels still remains unknown. This study was conducted to assess the plasma adiponectin levels in young men who were using dipping tobacco. METHODS: This was a community based study, which consisted of 186 young lean healthy males aged 20 to 35 years. Among these, 96 men were dipping tobacco users (BMI = 23.07 ± 2.68) and 90 were non-dipping tobacco users (BMI = 23.67 ± 1.46). Serum adiponectin levels were assessed by Enzyme Linked ImmunoSorbent Assay (ELISA). RESULTS: A statistically significant difference in the mean adiponectin level between tobacco dipper and non-dipper groups was observed (p = 0.0001). A significant difference between the two groups was also observed in baseline parameters including triglyceride and random blood sugar levels (p < 0.05). However, no significant difference was observed between the two groups in other clinical parameters. CONCLUSIONS: Findings of this study suggest that dipping tobacco use was significantly associated with low level of adiponetin in community dwelling young males. This emphasizes the importance of developing community intervention to reduce the use of dipping tobacco, which will reduce the tobacco associated disease burden in the community and will improve public health.

Nanoscale poly(4-hydroxybutyrate)-mPEG carriers for anticancer drugs delivery.

Despite several advancements in chemotherapy, cancer is still the second most frequent cause of mortality worldwide. Drug delivery to solid tumors is one of the most challenging aspects in cancer therapy. In pharmaceutical industries biodegradable polymeric nanoparticles as drug carriers have attracted great research interest because of their biocompatibility, biodegradability and sustained release of drugs. In our study we prepared poly(4-hydroxybutyrate)-mPEG (P(4HB)-mPEG) nanocarriers for the delivery of cisplatin as anticancer drug to mouse hippocampal HT22 cells. P(4HB) is more suitable candidate to be utilized in pharmaceutical industries due to its wide medical applications. P(4HB) is a homopolymer of 4-hydroxybutyrate (4HB), and belongs to a diverse class of materials called polyhydroxyalkanoates (PHA) produced by microorganisms inside the cells as energy storage materials. P(4HB) has certain unique properties such as biocompatibility and rapid in vivo degradation, which differentiate it from others PHA based polymers. Novel amorphous amphiphilic block copolymer P(4HB)-mPEG nanocarriers were prepared and characterized. Flow cytometry, and confocal microscopy revealed a suppression effect by the cisplatin loaded nanocarriers on HT22 cell growth, and enhancement of apoptotic process of the cells compared to free drug treated cells. The amorphous polymeric nanocarriers could be effective vehicles for the sustained delivery of toxic anticancer drugs for the therapy of cancer.

Intuitive weights of harm for therapeutic decision making in smear-negative pulmonary Tuberculosis: an interview study of physicians in India, Pakistan and Bangladesh.

BACKGROUND: To estimate the amount of regret and weights of harm by omission and commission during therapeutic decisions for smear-negative pulmonary Tuberculosis. METHODS: An interviewer-administered survey was done among young physicians in India, Pakistan and Bangladesh with a previously used questionnaire. The physicians were asked to estimate probabilities of morbidity and mortality related with disease and treatment and intuitive weights of omission and commission for treatment of suspected pulmonary Tuberculosis. A comparison with weights based on literature data was made. RESULTS: A total of 242 physicians completed the interview. Their mean age was 28 years, 158 (65.3%) were males. Median probability (%) of mortality and morbidity of disease was estimated at 65% (inter quartile range [IQR] 50-75) and 20% (IQR 8-30) respectively. Median probability of morbidity and mortality in case of occurrence of side effects was 15% (IQR 10-30) and 8% (IQR 5-20) respectively. Probability of absolute treatment mortality was 0.7% which was nearly eight times higher than 0.09% reported in the literature data. The omission vs. commission harm ratios based on intuitive weights, weights calculated with literature data, weights calculated with intuitive estimates of determinants adjusted without and with regret were 3.0 (1.4-5.0), 16 (11-26), 33 (11-98) and 48 (11-132) respectively. Thresholds based on pure regret and hybrid model (clinicians' intuitive estimates and regret) were 25 (16.7-41.7), and 2(0.75-7.5) respectively but utility-based thresholds for clinicians' estimates and literature data were 2.9 (1-8.3) and 5.9 (3.7-7.7) respectively. CONCLUSION: Intuitive weight of harm related to false-negatives was estimated higher than that to false-positives. The mortality related to treatment was eightfold overestimated. Adjusting expected utility thresholds for subjective regret had little effect.

Neurokinin B Administration Induces Dose Dependent Proliferation of Seminal Vesicles in Adult Rats.

BACKGROUND: Neurokinin B; an endogenous decapeptide, mediates its reproductive physiological actions through gonadotropin releasing hormone. Despite the potential role of Neurokinin B on seminal vesicles, its effects on seminal vesicles in adult male mammals remain elusive. We aimed to investigate the potentials of variable doses of Neurokinin B, its agonist and antagonist on histomorphology and expression of NK3R on seminal vesicles, and secretory activity of seminal vesicles in adult male rats. METHODS: Adult male Sprague Dawley rats (n=10 in each group) were administered intraperitoneally with Neurokinin B in three variable doses: 1 µg, 1 ηg and 10 ρg while, Senktide (Neurokinin B agonist) and SB222200 (Neurokinin B antagonist) in 1 µg doses consecutively for 12 days. After 12 days of peptide treatment, half of the animals (n=05) in each group were sacrificed while remaining half (n=05) were kept for another 12 days without any treatment to investigate treatment reversal. Seminal vesicles were dissected and excised tissue was processed for light microscopy, immunohistochemistry and estimation of seminal fructose levels. RESULTS: Treatment with Neurokinin B and Senktide significantly increased while SB222200 slightly decrease the seminal vesicles weight, epithelial height and seminal fructose levels as compared to control. Light microscopy revealed increased epithelial height and epithelial folding as compared to control in all Neurokinin B and Senktide treated groups while decreased in SB222200. Effects of various doses of Neurokinin B, Senktide and SB222200 on seminal vesicles weight, epithelial height, seminal fructose levels and histomorphology were reversed when rats were maintained without treatments. Immuno-expression of Neurokinin B shows no change in treatment and reversal groups. CONCLUSION: Continuous administration of Neurokinin B and Senktide effect positively while SB222200 have detrimental effects on cellular morphology, epithelial height and seminal fructose levels in seminal vesicles. Effects of peptide treatments depicted a reversal towards control group when rats were kept without any treatment.

Punicalagin improves inflammation and oxidative stress in rat model of pelvic inflammatory disease.

Pelvic inflammatory disease (PID) is one of the major public health concerns accounting for 30% of infertility and 50% of ectopic pregnancy cases due to severe inflammation and fibrosis. Punicalagin® are known to exhibit potent anti-inflammatory activity. The aim of this study was to demonstrate the anti-inflammatory and antioxidant effects of Punicalagin®, against pelvic inflammatory disease in rats. Female Sprague Dawley rats (n = 24) were divided into 6 groups (n = 4) as control, PID, prophylactic (low dose and high dose) and therapeutic group (low dose and high dose). PID model was constructed by implanting the rat cervix with mixed microbe (Escherichia Coli and Staphylococcus Aureus) solution. Prophylactic group was gavaged with 3 mg/kg (low dose) and 6 mg/kg (high dose) Punicalagin® daily starting one day before PID induction and therapeutic group was gavaged with 3 mg/kg (low dose) and 6 mg/kg (high dose) Punicalagin® daily starting 1 day after confirmation of PID model. Rats were sacrificed at the end of experiment and samples from upper genital tract were collected for ELISA, antioxidant assay and histopathological examination. According to results, obvious signs of inflammation and oxidative stress including infiltration of neutrophils and significantly raised levels of cytokines, and oxidative stress markers were observed in PID group when compared to control group. Punicalagin® significantly decreased the levels of IL-1ß, catalase and lipid peroxidation in both prophylactic and therapeutic groups when compared to PID group. Punicalagin® also decreased the infiltration of leucocytes in uterus of prophylactic and therapeutic group when compared to PID group, as determined by histological examination. On basis of these results, we concluded that Punicalagin® showed anti-inflammatory and antioxidant potential in rat model of pelvic inflammatory disease and could be used as possible therapeutic agent in treatment of PID.

Cross-cultural adaptation and psychometric validation of the brief assessment of recovery capital (BARC-10) scale into Bangla.

Recovery capital is a construct central to the substance use disorder treatment and recovery field. Lack of structured instrument for its assessment in the local context necessitated the translation of the English self-assessment version of the "Brief Assessment of Recovery Capital" (BARC-10) scale to Bangla and the study of its psychometric properties. The objective was to develop a culturally adapted and validated Bangla version of the BARC-10 scale for substance use disorders patients. This study conducted in the period of January 2021 to March 2022 in the department of Psychiatry of a tertiary hospital and central drug addiction treatment center. Initially BARC-10 questionnaire was translated into Bangla (T1 and T2) by 2 separate translators and then synthesis of a single version (T12) was done based on the previous translations. After that 2 back translations (BT1 and BT2) were done by 2 more translators based on the synthesized version (T12). By reviewing all these forward and backward translations, an expert committee made the pre-final version after making some linguistic modification. Then data collection was done among 100 subjects who were selected purposively. Reliability was assessed by Cronbach alpha. Content validity, face validity and Construct validity by factor analysis were measured. Internal consistency measured by Cronbach alpha found was 0.846. No significant change in Cronbach alpha was observed following deleting any item. Confirmatory factor analysis revealed a good fit to data by a chi-square/df value1.33, RMSEA value 0.058. Kaiser-Meyer-Olkin value (.840) showed sampling adequacy. Exploratory factor analysis of the principal component identified 2 factors which had eigenvalues of more than 1. Scree plot also revealed similar factors. These 2 factors together explained 53.1% of the variance. All items were loaded under 2 factors after varimax rotation. The validated Bangla version of the BARC-10 demonstrated high internal reliability and validity. It can potentially be applied in "recovery-oriented" deaddiction service.