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.

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.

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.

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.

Maternal serum interleukin 6 and 8 and C-reactive protein in predicting the tocolytic therapy in preterm labor.

BACKGROUND: This study aimed to evaluate the relation between C-reactive protein (CRP), interleukin (IL) 6 and 8 with the response to tocolytic therapy. MATERIALS AND METHODS: A total of 75 singleton pregnant women between 18 and 35 years old, and with symptoms of preterm labor were hospitalized in "Shahid Beheshti" hospital in Isfahan, Iran. Tocolysis in patients was performed first with infusion of 4 g of magnesium sulfate 20% and then 2 g per hour continued. Next, they were followed till delivery time to assess the response to the treatment. Baseline data and serum levels of IL-6 and IL-8 and CRP were all recorded. RESULTS: A total of 16 patients with symptoms of preterm labor did not respond to the treatment and delivered prematurely and 59 women responded to tocolytic treatment and delivered at term. There was a significant relationship between serum IL-6, IL-8 and CRP levels with response to the treatment in cut-off > 45 for IL-6 [area under the curve [(AUC), 0.894; SE, 0.042; P-value < 0.0001, >171 for IL-8 (AUC, 0.864; SE, 0.059; P-value < 0.0001)] and >1.8 for CRP (AUC, 0.738; SE, 0.076; P-value = 0.001). Also, pairwise comparison of receiver operating characteristic curves between CRP, IL-6, and IL-8 showed that there were no significant differences between areas for IL-6 with IL-8 (P-value = 0.46); IL-6 with CRP (P-value = 0.086); and IL-8 with CRP (P-value = 0.18). CONCLUSION: Maternal serum concentrations of IL-6 and IL-8 and CRP can be used as appropriate biomarkers for predicting the response to tocolytic therapy in pregnant women and there were no significant differences between these markers in predicting tocolytic therapy.

A case of placental polyp after normal vaginal delivery.

Placental polyp is retained placental tissue within the endometrial cavity, which forms a nidus for inflammation and bleeding. There are very few reported cases of the clinical placental polyp. Here, we report a case of 34-year-old G4L3Ab1 woman with the chief complaint of intermittent vaginal bleeding since her last normal vaginal delivery 3 months ago. Serum human chorionic gonadotropin (hCG) titer was slightly elevated. A polypoid mass was detected within the endometrial cavity by imaging studies. History of the patient, mass lesion within the endometrial cavity and slightly elevated serum hCG titer raised the suspicion of trophoblastic neoplasms. Endometrial curettage yielded unsatisfactory specimen containing only fibrin deposition and was followed by total hysterectomy. The uterus showed slight global enlargement resulting from the presence of a polypoid mass within the endometrial cavity. The red-colored mass had a smooth outer surface and fragile consistency without any permeation into the myometrium. Pathology reported it as the placental polyp. Although very rare, placental polyp should be kept in mind as one of the reasons of abnormal uterine bleeding in parous women. Definite diagnosis is made by pathology examination.

Complete bicornuate uterus with complete transverse vaginal septum.

Bicornuate uterus has two symmetric uterine cavities that are fused caudally and have some degree of communication between two cavities, usually at the uterine isthmus. A complete bicornuate uterus has a seperatory cleft of tissue that is extended to the internal OS. Lesser degree of septation of the two uterine horns has constitution, a partial bicornuate uterus. Bicornuate uterus is a class of four anomaly of American fertility society classification of mullerian anomalies. Here we report a case of a 19-year-old female patient with complaint of abdominal pain and spotting since 4 months ago. In sonography it revealed bicornuate uterus and hematocolpos. The patient underwent general anesthesia and examination that reveal the transverse vaginal septum. Septum removed by resectoscope was successful.

The effect of celastrol in combination with 5-fluorouracil on proliferation and apoptosis of gastric cancer cell lines.

Background: Despite the availability of chemotherapy drugs such as 5-fluorouracil (5-FU), the treatment of some cancers such as gastric cancer remains challenging due to drug resistance and side effects. This study aimed to investigate the effect of celastrol in combination with the chemotherapy drug 5-FU on proliferation and induction of apoptosis in human gastric cancer cell lines (AGS and EPG85-257). Materials and Methods: In this in vitro study, AGS and EPG85-257 cells were treated with different concentrations of celastrol, 5-FU, and their combination. Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The synergistic effect of 5-FU and celastrol was studied using Compusyn software. The DNA content at different phases of the cell cycle and apoptosis rate was measured using flow cytometry. Results: Co-treatment with low concentrations (10% inhibitory concentration (IC10)) of celastrol and 5-FU significantly reduced IC50 (p < 0.05) so that 48 h after treatment, IC50 was calculated at 3.77 and 6.9 µM for celastrol, 20.7 and 11.6 µM for 5-FU, and 5.03 and 4.57 µM for their combination for AGS and EPG85-257 cells, respectively. The mean percentage of apoptosis for AGS cells treated with celastrol, 5-FU, and their combination was obtained 23.9, 41.2, and 61.9, and for EPG85-257 cells 5.65, 46.9, and 55.7, respectively. In addition, the 5-FU and celastrol-5-FU combination induced cell cycle arrest in the synthesis phase. Conclusions: Although celastrol could decrease the concentration of 5-fluorouracil that sufficed to suppress gastric cancer cells, additional studies are required to arrive at conclusive evidence on the anticancer effects of celastrol.

Gender-Affirming Hormone Treatment and Metabolic Syndrome Among Transgender Veterans.

Importance: Gender-affirming hormone treatment (GAHT) is a common therapy for transgender individuals to reduce gender dysphoria and improve quality of life. Clarifying the long-term effects of GAHT remains a priority in transgender health research. Objective: To explore whether sex hormones (estradiol and testosterone) are associated with the development of metabolic syndrome in transgender veterans compared with cisgender veterans. Design, Setting, and Participants: This retrospective, longitudinal cohort study used International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes for gender dysphoria from the Veterans Health Administration national database to identify transfeminine and transmasculine veterans receiving documented feminizing (estradiol) or masculinizing (testosterone) treatment from January 1, 2006, to December 31, 2019, and for whom the GAHT initiation date and metabolic syndrome component-related data were available. Transgender veterans were matched to cisgender referents. Exposure: Gender-affirming hormone treatment. Main Outcomes and Measures: Metabolic syndrome z-scores were calculated based on body mass index, systolic blood pressure, and levels of high-density lipoprotein cholesterol, triglycerides, and blood glucose. Changes in mean z-scores were compared among the transgender and cisgender groups before and after the index date (corresponding to GAHT initiation) using a repeated-measures analysis of variance model. Results: The cohort included 1290 participants: 645 transgender (494 [38.3%] transfeminine, 151 [11.7%] transmasculine) and 645 cisgender (280 [21.7%] female, 365 [28.3%] male). Mean (SD) age at the index date was 41.3 (13.2) years. Metabolic syndrome z-scores changed significantly over time and differed significantly across groups. Overall, transmasculine veterans had the greatest percentage increase in mean (SEM) z-scores after vs before the index date (298.0% [57.0%]; P < .001), followed by cisgender females (108.3% [27.5%]; P < .001), cisgender males (49.3% [27.5%]; P = .02), and transfeminine persons (3.0% [10.7%]; P = .77). Conclusions and Relevance: In this cohort study, in both cisgender and transgender veterans, estradiol was associated with reduced metabolic syndrome risk, whereas testosterone was associated with increased risk. However, transmasculine individuals had the greatest risk and transfeminine individuals had the lowest risk of metabolic syndrome associated with these hormones. This is relevant for the management of metabolic syndrome risk factors in cisgender and transgender individuals and to potentially predict the risk of atherosclerotic cardiovascular disease, type 2 diabetes, systolic hypertension, insulin resistance, and nonalcoholic fatty liver disease.

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.

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.

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.

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.

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.

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.

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.

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.

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.