Ferulago angulata Methanolic Extract Protects PC12 Cells Against Beta-amyloid-induced Toxicity.

Introduction: Alzheimer's disease (AD) is an age-dependent neurodegenerative disease. Beta-amyloid (Aß)-induced neurotoxicity has a pivotal role in AD pathogenesis; therefore, the modulation of Aß toxicity is the promising therapeutic approach to control the disease progression. Medicinal plants because of their multiple active ingredients are effective in complex diseases, such as AD. Therefore, several studies have studied medicinal plants to find an effective treatment for AD. Ferulago angulata is a medicinal plant with antioxidant and neuroprotective activity. The present study was done to assess the protective effect of the methanolic extract of Ferulago angulate on Aß-induced toxicity and oxidative stress in PC12 cells. Methods: The methanolic extract of aerial parts of the plant was prepared by the maceration method. PC12 cells were cultured according to a standard protocol. PC12 cells were incubated for 24 hours with Aß alone, and Aß in combination with various concentrations of the F. angulata extract. Cell viability was determined by the methyl thiazole tetrazolium (MTT) assay. Also, reactive oxygen species (ROS) production and the activity of acetylcholine esterase (AChE), glutathione peroxidase (GPx), and caspase-3 enzymes were measured. Results: The extract dose-dependently protected PC12 cells against Aß-induced cell death. Also, Aß increased ROS production, AChE, and caspase-3 activity, and decreased the GPx activity, which all were ameliorated by F. angulata extract. Conclusion: F. angulata extract protects against Aß-induced oxidative stress and apoptosis. These effects may be due to the antioxidant and anticholinesterase activity of the extract. It is recommended to assess F. angulata extract as an anti-AD agent. Highlights: Ferulago angulata extract dose-dependently ameliorates Aß-induced cytotoxicity in PC12 cells.Aß induced oxidative stress in PC12 cells, which was attenuated by the F. angulata extract.Aß increased acetylcholinesterase activity in PC12 cells, which was prevented by the F. angulata extract. Plain Language Summary: Alzheimer's disease (AD) is a common form of dementia in the elderly with a complex pathophysiology. Beta-amyloid (Aß)- induced neurotoxicity plays a pivotal role in AD progression. So far, there is no cure for AD. Medicinal plants contain various pharmacologically active compounds that make them suitable for the treatment of complex diseases. In this study, the anti-AD effect of F. angulata extract was investigated by assessing its protective effect against Aß-induced toxicity in PC12 cells F. angulata extract improved Aß-induced toxicity by diminishing oxidative stress and apoptosis. Therefore, F. angulata extract merits further studies for use in the treatment of AD.

Triglycerides and Renal Outcomes According to Albuminuria and in Consideration of Other Metabolic Syndrome Components in Diabetic US Veterans.

INTRODUCTION: Hypertriglyceridemia, a component of the metabolic syndrome, is a known independent predictor of albuminuria and chronic kidney disease (CKD) in the general population. Previous studies have shown that the relationship of triglycerides (TGs) with outcomes changes across stages of CKD. Our objective was to examine the association of TG independent of other metabolic syndrome components with renal outcomes in diabetic patients with or without CKD. METHODS: This retrospective cohort study included diabetic US veteran patients with valid data on TGs, estimated glomerular filtration rate (eGFR), and albuminuria (urinary albumin/creatinine ratio) between fiscal years 2004 and 2006. Using Cox models adjusted for clinical characteristics and laboratory markers, we evaluated the relationship of TG with incident albuminuria (stratified by eGFR category) and based on eGFR (stratified by baseline albuminuria categories). To evaluate the relationship of TG with time to end-stage renal disease (ESRD), we stratified models by baseline CKD stage (eGFR category) and baseline albuminuria stage ascertained at time of TG measurement. RESULTS: In a cohort of 138,675 diabetic veterans, the mean ± SD age was 65 ± 11 years old and included 3% females and 14% African Americans. The cohort also included 28% of patients with non-dialysis-dependent CKD (eGFR <60 mL/min/1.73 m2), as well as 28% of patients with albuminuria (≥30 mg/g). The median (IQR) of serum TG was 148 (100, 222) mg/dL. We observed a slight positive linear association between TG and incident CKD after adjustment for Case-Mix and Laboratory variables among non-albuminuric and microalbuminuric patients. The relationship of high TG trended towards a higher risk of ESRD in CKD 3A non-albuminuric patients and in CKD 3A and 4/5 patients with microalbuminuria. CONCLUSION: In a large cohort, we have shown that elevated TGs are associated with all kidney outcomes tested independently of other metabolic syndrome components in diabetic patients with normal eGFR and normal albumin excretion rate, but the association is weaker in some groups of diabetic patients with preexisting renal complications.

Hepatitis C Virus Testing and Care Cascade Among Transgender and Gender Diverse Individuals.

INTRODUCTION: Hepatitis C virus (HCV) prevalence among transgender and gender-diverse individuals ranges from 1.8% to 15.7% versus 1% in the general population. Previous HCV studies inclusive of transgender and gender-diverse individuals primarily rely on convenience-based sampling methods or are geographically restricted. The purpose of this study is to compare the prevalence of HCV diagnoses, testing, and care engagement between transgender and gender-diverse and cisgender individuals. METHODS: Using Optum's de-identified Clinformatics® Data Mart Database, in 2022, the unadjusted prevalence of HCV testing among all adults and people who inject drugs from January 2001 to December 2019 was measured. Multivariable logistic regression was used to compare the adjusted odds of HCV diagnoses and care engagement by gender subgroup. RESULTS: The overall unadjusted frequency of HCV diagnoses among transgender and gender-diverse individuals was approximately 3 times that of cisgender individuals (1.06% vs 0.38%, p<0.001), including among people who inject drugs (6.36% vs 2.36%, p=0.007). Compared with cisgender women, transfeminine/nonbinary individuals had over 5 times the adjusted odds of a HCV diagnosis and approximately 3.5 times the odds of being tested for HCV. In addition, compared with cisgender women, transfeminine/nonbinary individuals had significantly increased odds of having a HCV‒related procedure (e.g., abdominal ultrasounds, liver biopsies, Fibroscans). Cisgender men had significantly increased odds of receiving HCV medication compared with cisgender women. CONCLUSIONS: Although testing was higher among transgender and gender-diverse individuals, the higher overall frequency of HCV diagnoses among transgender and gender-diverse than among cisgender individuals signals persistent health disparities. Interventions are warranted to prevent HCV and increase ongoing testing and treatment uptake among transgender and gender-diverse populations.

Chromosome number, sex determination, and meiotic chromosome behavior in the praying mantid Hierodula membranacea.

Praying mantids are important models for studying a wide range of chromosome behaviors, yet few species of mantids have been characterized chromosomally. Here we show that the praying mantid Hierodula membranacea has a chromosome number of 2n = 27, and X1X1X2X2 (female): X1X2Y (male) sex determination. In male meiosis I, the X1, X2, and Y chromosomes of H. membranacea form a sex trivalent, with the Y chromosome associating with one spindle pole and the X1 and X2 chromosomes facing the opposite spindle pole. While it is possible that such a sex trivalent could experience different spindle forces on each side of the trivalent, in H. membranacea the sex trivalent aligns at the spindle equator with all of the autosomes, and then the sex chromosomes separate in anaphase I simultaneously with the autosomes. With this observation, H. membranacea can be used as a model system to study the balance of forces acting on a trivalent during meiosis I and analyze the functional importance of chromosome alignment in metaphase as a preparatory step for subsequent correct chromosome segregation.

Association of Serum Triglycerides and Renal Outcomes among 1.6 Million US Veterans.

BACKGROUND: Previous studies have suggested that metabolic syndrome (MetS) components are associated with renal outcomes, defined as a decline in kidney function or reaching end-stage renal disease (ESRD). Elevated triglycerides (TGs) are a component of MetS that have been reported to be associated with renal outcomes. However, the association of TGs with renal outcomes in chronic kidney disease (CKD) patients independent of the other components of the MetS remains understudied. METHODS: We examined 1,657,387 patients with data on TGs and other components of MetS in 2004-2006 and followed up until 2014. Patients with ESRD on renal replacement therapy were excluded. We examined time to ESRD, estimated glomerular filtration rate (eGFR) slope (renal function decline), and time to incident CKD (eGFR <60 mL/min/1.73 m2) among baseline normal kidney function (non-CKD) patients, using Cox or logistic regression, adjusted for clinical characteristics and MetS components. We also stratified analyses by the number of MetS components. RESULTS: The cohort was on average 64 years old and comprised 5% females, 15% African Americans, and 24% with nondialysis-dependent CKD. Among non-CKD patients, the adjusted relationship of TGs with time to incident CKD was strong and linear. Compared to TGs 120-<160 mg/dL, higher TGs were associated with a faster renal function decline across all CKD stages. Elevated TGs ≥240 mg/dL were associated with a faster time to ESRD among non-CKD and CKD stages 3A-3B, while the risk gradually declined to null or lower in CKD stages 4-5. Models were robust after MetS component adjustment and stratification. CONCLUSION: Independent of MetS components, high TGs levels were associated with a higher incidence of CKD and a faster renal function decline, yet showed no or inverse associations with time to ESRD in CKD stages 4-5. Examining the effects of TGs-lowering interventions on incident CKD and kidney preserving therapy warrants further studies including clinical trials.

Serum Low-Density Lipoprotein Cholesterol and Cardiovascular Disease Risk Across Chronic Kidney Disease Stages (Data from 1.9 Million United States Veterans).

In the general population, elevated low-density lipoprotein (LDL) cholesterol levels are an important risk factor for cardiovascular disease (CVD) and mortality; however, the association of LDL with mortality risk and cardiovascular events are less clear in chronic kidney disease (CKD). We sought to examine the relationship of LDL with mortality and rates of atherosclerotic cardiovascular disease (ASCVD) and non-atherosclerotic cardiovascular-related (non-ASCVD) hospitalizations across CKD stages. Our analytical cohort consisted of 1,972,851 United States veterans with serum LDL data between 2004 and 2006. Associations of LDL with all-cause and cardiovascular mortality across CKD stages were evaluated using Cox proportional hazard models with adjustment for demographics, comorbid conditions, smoking status, prescription of statins and non-statin lipid-lowering drugs, body mass index, albumin, high-density lipoprotein, and triglycerides. Associations between LDL and ASCVD and non-ASCVD hospitalizations were estimated using negative binomial regression models across CKD stages. The cohort consisted of 5% female, 14% Black, 29% diabetic, 33% statin-users, and 44% current smokers, with a mean patient age of 64 ± 14 years. Patients with high LDL (≥160 mg/dL) had a higher risk of all-cause and cardiovascular mortality as well as ASCVD and non-ASCVD hospitalization rates across all CKD stages compared with the reference (LDL 70 to <100 mg/dL). The associations with all-cause and cardiovascular mortality and ASCVD hospitalization rate were attenuated at higher CKD stages. These trends were reversed with amplification of the association of high LDL with non-ASCVD hospitalization at higher CKD stages. In conclusion, associations of LDL with mortality and both ASCVD and non-ASCVD hospitalizations are modified according to kidney disease stage.

Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Use Associated with Reduced Mortality and Other Disease Outcomes in US Veterans with COVID-19.

OBJECTIVE: To determine the association between angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) use and coronavirus disease 2019 (COVID-19) severity and outcomes in US veterans. PATIENTS AND METHODS: We retrospectively examined 27,556 adult US veterans who tested positive for COVID-19 between March to November 2020. Logistic regression and Cox proportional hazards models using propensity score (PS) for weight, adjustment, and matching were used to examine the odds of an event within 60 days following a COVID-19-positive case date and time to death, respectively, according to ACEI and/or ARB prescription within 6 months prior to the COVID-19-positive case date. RESULTS: The overlap PS weighted logistic regression model showed lower odds of an intensive care unit (ICU) admission (odds ratio [OR] 95% CI 0.77, 0.61-0.98) and death within 60 days (0.87, 0.79-0.97) with an ACEI or ARB prescription. Veterans with an ARB-only prescription also had lower odds of an ICU admission (0.64, 0.44-0.92). The overlap PS weighted model similarly showed a lower risk of time to all-cause mortality in veterans with an ACEI or ARB prescription (HR [95% CI]: 0.87, 0.79-0.97) and an ARB only prescription (0.78, 0.67-0.91). Veterans with an ACEI prescription had higher odds of experiencing a septic event within 60 days after the COVID-19-positive case date (1.22, 1.02-1.46). CONCLUSION: In this study of a national cohort of US veterans, we found that the use of an ACEI/ARB in patients with COVID-19 was not associated with increased mortality and other worse outcomes. Future studies should examine underlying pathways and further confirm the relationship of ACEI prescription with sepsis.

Risk of Atherosclerotic Cardiovascular Disease and Nonatherosclerotic Cardiovascular Disease Hospitalizations for Triglycerides Across Chronic Kidney Disease Stages Among 2.9 Million US Veterans.

Background High triglycerides are associated with atherosclerotic cardiovascular disease (ASCVD) risks. Among patients with advanced chronic kidney disease (CKD), the association of elevated triglycerides with mortality is diminished and, thus, we investigated the relationship of triglycerides with ASCVD and non-ASCVD hospitalizations across CKD stages. Methods and Results The cohort comprised 2 963 176 veterans who received care in 2004 to 2006 (baseline) and were followed up to 2014. Using Cox models, we evaluated baseline and time-varying triglycerides with time to ASCVD or non-ASCVD hospitalizations, stratified by baseline CKD stage, and adjusted for demographics and baseline or time-updated clinical characteristics. The cohort mean±SD age was 63±14 years, with a baseline median (interquartile range) triglycerides level of 127 (87-189) mg/dL, and a quarter had prevalent CKD. There was a linear association between baseline triglycerides and ASCVD risk; however, the risk with high triglycerides ≥240 mg/dL attenuated with worsening CKD stages (reference: triglycerides 120 to <160 mg/dL). Baseline triglycerides were associated with a U-shaped relationship for non-ASCVD events in patients with CKD 3A to 3B. Patients with late-stage CKD had lower to null relationships between baseline triglycerides and non-ASCVD events. Time-varying triglycerides associations with ASCVD were similar to baseline analyses. Yet, the time-varying triglycerides relationship with non-ASCVD events was inverse and linear, where elevated triglycerides were associated with lower risks. Conclusions Associations of higher triglycerides with ASCVD and non-ASCVD events declined across advancing CKD stages, where a lower to null risk was observed in patients with advanced CKD. Studies are needed to examine the impact of advanced CKD on triglycerides metabolism and its association with outcomes in this high-risk population.

Validating Data-Driven Methods for Identifying Transgender Individuals in the Veterans Health Administration of the US Department of Veterans Affairs.

We sought to operationalize and validate data-driven approaches for identifying transgender individuals in the Veterans Health Administration (VHA) of the US Department of Veterans Affairs (VA) through a retrospective analysis using VA administrative data from 2006-2018. Besides diagnoses of gender identity disorder (GID), a combination of non-GID data elements was used to identify potentially transgender veterans, including 1) an International Classification of Diseases (Ninth or Tenth Revision) code of endocrine disorder, unspecified or not otherwise specified; 2) receipt of sex hormones not associated with the sex documented in the veteran's records (gender-affirming hormone therapy); and 3) a change in the veteran's administratively recorded sex. Both GID and non-GID data elements were applied to a sample of 13,233,529 veterans utilizing the VHA of the VA between January 2006 and December 2018. We identified 10,769 potentially transgender veterans. Based on a high positive predictive value for GID-coded veterans (83%, 95% confidence interval: 77, 89) versus non-GID-coded veterans (2%, 95% confidence interval: 1, 11) from chart review validation, the final analytical sample comprised only veterans with a GID diagnosis code (n = 9,608). In the absence of self-identified gender identity, findings suggest that relying entirely on GID diagnosis codes is the most reliable approach for identifying transgender individuals in the VHA of the VA.

Longitudinal Changes in Liver Enzyme Levels Among Transgender People Receiving Gender Affirming Hormone Therapy.

BACKGROUND: The effect of gender affirming hormone therapy (GAHT) on clinical laboratory parameters, including levels of liver enzymes alanine aminotransferase (ALT) and aspartate transaminase (AST), is an area of uncertainty in transgender health. AIM: We sought to estimate the distribution parameters of liver enzyme levels among transmasculine (TM) and transfeminine (TF) persons receiving GAHT relative to the corresponding measures in cisgender reference groups, and to evaluate longitudinal changes in these laboratory measures following GAHT initiation. METHODS: The data for this longitudinal study included 624 TF and 438 transmasculine (TM) people as well as 4,090 cisgender males and 4,797 cisgender females enrolled in 3 integrated health systems. Time under observation was divided into 2 intervals: from the first blood test to the date of the first filled GAHT prescription and from GAHT initiation to the most recent ALT or AST measurement. Linear mixed models were used to compare changes in log-transformed ALT and AST values among transgender cohort members before and after GAHT initiation, and relative to the reference groups. The results were expressed as relative differences (in %) and the ratios of these differences (ratios-of-ratios) along with the 95% confidence intervals (CIs). OUTCOMES: Changes in ALT and AST levels among transgender people over time and relative to the corresponding changes in cisgender referents. RESULTS: Among TM study participants, the post GAHT ratios-of-ratios for AST were 1.61 (95% CI: 1.13, 2.31) and 1.57 (95% CI: 1.06, 2.31) relative to cisgender males and females respectively. For ALT, the corresponding comparisons yielded the ratios-of-ratios (95% CIs) of 2.06 (1.67, 2.54) and 1.90 (1.50, 2.40). No statistically significant changes were observed among TF participants. Other factors associated with higher liver enzyme levels included alcohol use/abuse and obesity. CLINICAL IMPLICATIONS: TM persons may experience modest increases in ALT and AST concentrations following testosterone initiation; however, clinical significance of the observed association remains unclear and requires further investigation. By contrast, feminizing GAHT is unlikely to induce appreciable changes in liver enzyme levels. STRENGTH AND LIMITATIONS: The strengths of this study are the longitudinal design and the ability to assemble an unselected cohort nested within large health systems. The main limitations include the lack of information on hormone levels and the inability to take into account GAHT doses and routes of administration. CONCLUSION: The influence of long-term GAHT on ALT and AST levels appears modest and not likely to reflect clinically meaningful changes in liver function. Hashemi L, Zhang Q, Getahun D, et al. Longitudinal Changes in Liver Enzyme Levels Among Transgender People Receiving Gender Affirming Hormone Therapy. J Sex Med 2021;18:1662-1675.

Pore-scale modelling and sensitivity analyses of hydrogen-brine multiphase flow in geological porous media.

Underground hydrogen storage (UHS) in initially brine-saturated deep porous rocks is a promising large-scale energy storage technology, due to hydrogen's high specific energy capacity and the high volumetric capacity of aquifers. Appropriate selection of a feasible and safe storage site vitally depends on understanding hydrogen transport characteristics in the subsurface. Unfortunately there exist no robust experimental analyses in the literature to properly characterise this complex process. As such, in this work, we present a systematic pore-scale modelling study to quantify the crucial reservoir-scale functions of relative permeability and capillary pressure and their dependencies on fluid and reservoir rock conditions. To conduct a conclusive study, in the absence of sufficient experimental data, a rigorous sensitivity analysis has been performed to quantify the impacts of uncertain fluid and rock properties on these upscaled functions. The parameters are varied around a base-case, which is obtained through matching to the existing experimental study. Moreover, cyclic hysteretic multiphase flow is also studied, which is a relevant aspect for cyclic hydrogen-brine energy storage projects. The present study applies pore-scale analysis to predict the flow of hydrogen in storage formations, and to quantify the sensitivity to the micro-scale characteristics of contact angle (i.e., wettability) and porous rock structure.

The quest for cardiovascular disease risk prediction models in patients with nondialysis chronic kidney disease.

PURPOSE OF REVIEW: Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). However, traditional CVD risk prediction equations do not work well in patients with CKD, and inclusion of kidney disease metrics such as albuminuria and estimated glomerular filtration rate have a modest to no benefit in improving prediction. RECENT FINDINGS: As CKD progresses, the strength of traditional CVD risk factors in predicting clinical outcomes weakens. A pooled cohort equation used for CVD risk prediction is a useful tool for guiding clinicians on management of patients with CVD risk, but these equations do not calibrate well in patients with CKD, although a number of studies have developed modifications of the traditional equations to improve risk prediction. The reason for the poor calibration may be related to the fact that as CKD progresses, associations of traditional risk factors such as BMI, lipids and blood pressure with CVD outcomes are attenuated or reverse, and other risk factors may become more important. SUMMARY: Large national cohorts such as the US Veteran cohort with many patients with evolving CKD may be useful resources for the developing CVD prediction models; however, additional considerations are needed for the unique composition of patients receiving care in these healthcare systems, including those with multiple comorbidities, as well as mental health issues, homelessness, posttraumatic stress disorders, frailty, malnutrition and polypharmacy. Machine learning over conventional risk prediction models may be better suited to handle the complexity needed for these CVD prediction models.

Epidemiological considerations in transgender health: A systematic review with focus on higher quality data.

Background: High quality data pertaining to the size of the transgender and gender diverse (TGD) population are scant, however, several recently published studies may provide more reliable contemporary estimates. Aims: To summarize the estimated number and proportion of TGD individuals overall and across age groups, based on most accurate data. Methods: This systematic review focused on recent studies (published from 2009 through 2019) that utilized sound methodology in assessing the proportion of TGD people in the general population. Publications were included if they used clear definitions of TGD status, and calculated proportions based on a well-defined sampling frame. Nineteen eligible publications represented two broad categories of studies: those that used data from large health care systems; and those that identified TGD individuals from population surveys. Results: Among health system-based studies, TGD persons were identified using relevant diagnostic codes or clinical notes. The proportions of individuals with a TGD-relevant diagnosis or other recorded evidence ranged between 17 and 33 per 100,000 enrollees. In population surveys TGD status was ascertained based on self-report with either narrow or broad definitions. The survey-based estimates were orders of magnitude higher and consistent across studies using similar definitions. When the surveys specifically inquired about 'transgender' identity, the estimates ranged from 0.3% to 0.5% among adults, and from 1.2% to 2.7% among children and adolescents. When the definition was expanded to include broader manifestations of 'gender diversity', the corresponding proportions increased to 0.5-4.5% among adults and 2.5-8.4% among children and adolescents. Upward temporal trends in the proportion of TGD people were consistently observed. Conclusions: Current data indicate that people who self-identify as TGD represent a sizable and increasing proportion of the general population. This proportion may differ, depending on inclusion criteria, age, and geographic location, but well-conducted studies of similar type and design tend to produce comparable results.

A Case-Based Review of Iron Overload With an Emphasis on Porphyria Cutanea Tarda, Hepatitis C, C282Y Heterozygosity, and Coronary Artery Disease.

Iron overload can impact disease progression and treatment options for patients with comorbid conditions, such as porphyria cutanea tarda, hepatitis C virus, and coronary artery disease.

Incidentally Discovered Ochronosis Explaining Decades of Chronic Pain.

Although commonly detected early in life, alkaptonuria, a rare congenital metabolic disorder, can be challenging to diagnosis and treat in older patients.

Early Marriage and Negative Life Events Affect on Depression in Young Adults and Adolescents.

BACKGROUND: Negative life events (NLEs) and early marriage (EM), a worldwide social silent problem, are increasing in prevalence globally. Evidence is lacking regarding their impact on depression. We assessed the impact of EM and NLEs on depression among adolescents, young adults and adults in Iran. METHODS: A population-based descriptive study was performed among urban and rural population aged 13-40 years. Beck depression inventory scale II and life event questionnaire were used to assess the severity of depression and NLEs, respectively. EM was defined as a marriage or union between two persons in which one or both parties are younger than 18. RESULTS: In a total of 530 participants (300 female and 230 male) with a mean age of 26.78 ± 5.06, almost 46% had depressive symptoms. A trend was found between rising age and depression so that among the three groups of study subjects, adults had the highest prevalence rate (49.34%). After adjusting for age, residence, substance abuse, alcohol abuse, unemployment and other NLEs by multiple regression, we found statistically significant relationships between depression and EM (2.77; CI: 1.75-4.57), and NLEs (2.78; CI: 1.85-4.19). Among types of NLEs, marital conflicts (5.8; CI: 1.60-20.81), loss of loved ones (6.12; CI: 1.28-28.26) and financial problems (13.79; CI: 1.72-108.17) were associated with depression risk. CONCLUSION: Life skills improving program with intersectoral collaborative care to reduce determinants of EM and NLEs in the community, as well as training and screening for depression among adolescents and adulthood are necessary.

Anti-Influenza Virus Activity and Phenolic Content of Pomegranate (Punica granatum L.) Peel Extract and Fractions.

BACKGROUND: Influenza virus, associated with high level of morbidity and mortality, has been recently considered a public health concern while the choices for the control and treatment of the disease are limited. The present study was conducted to evaluate activity of pomegranate peel extract and its fractions against Influenza A virus in vitro . METHODS: In this research, ethyl alcohol extract of pomegranate peel was prepared and subjected to fractionation with different polarities. The potential in vitro anti-influenza A virus activity of the extract and fractions was assessed using Cytopathic Effect (CPE) reduction assay, Hemagglutinin Assay (HA), and 50% Tissue Culture Infectious Doses (TCID50) method in Madin-Darby Canine Kidney (MDCK) cells. RESULTS: The crude pomegranate peel extract and its n-butanol and ethyl acetate fractions had the highest inhibitory effect against influenza A virus with IC50 value of 6.45, 6.07 and 5.6 µg/ml in MDCK cells, respectively. Our results also showed that, the production of virus was significantly reduced upon treatment with crude extract, n-butanol and ethyl acetate fractions in a dose-dependent manner (p<0.05). CONCLUSION: Based on our results, the ethyl alcohol extract and its polar fractions of pomegranate peel can inhibit influenza A virus replication in vitro. Therefore, further characterization of its active ingredients and the mechanism of action should be carried out.

Natural cycle versus artificial cycle in frozen-thawed embryo transfer: A randomized prospective trial.

OBJECTIVE: To investigate whether there was a difference in pregnancy outcomes between modified natural cycle frozen-thawed embryo transfer (NC-FET) cycles and artificial cycles (AC)-FET in women who all had regular menstrual cycles. MATERIALS AND METHODS: One hundred seventy patients who met the inclusion criteria and had at least two cryopreserved embryos were included in a prospective randomized controlled trial. Eighty-five patients were randomized based on Bernoulli distribution into the following two groups: 1) Modified NC-FET using human chorionic gonadotropin for ovulation induction and 2) AC-FET, in which endometrial timing was programmed with estrogen and progesterone. The main studied outcome measure was the clinical pregnancy rate per cycle. RESULTS: No significant differences were found between the two groups with regard to the chemical, clinical, and ongoing pregnancy rates (48.2% vs 45.9%, p>0.05; 38.9% vs 35.3%, p>0.05; and 37.6% vs 34.1%, p>0.05, respectively), as well as the live birth or miscarriage rates per cycle (35.3% vs 31.8%, p>0.05; and 1.2% vs 1.2%, p>0.05, respectively). CONCLUSION: These findings suggest that although both FET protocols are equally effective in terms of pregnancy outcomes in women with regular menstrual cycles, NC-FET is more favorable because it requires no medication, has no adverse events, and has a significant cost reduction.

The Clinical Pathophysiology of Chronic Systemic Sclerosis.

Primary care providers should monitor disease progression in the skin and in the pulmonary, renal, cardiac, and gastrointestinal systems in patients with systemic sclerosis, a rare autoimmune and connective tissue disease.

Transgender Care in the Primary Care Setting: A Review of Guidelines and Literature.

For patients who desire transgender care, providers must use appropriate language, know the basics of cross-sex hormone therapy, and understand the risks and adverse effects of treatment options.