Impact of contact lens hygiene risk factors on the prevalence of contact lens-related keratitis in Alexandria-Egypt.

BACKGROUND: This study aimed at measuring the effect of contact lens hygiene risk factors on the prevalence of contact lens-related keratitis and identifying the specific risk factors to both microbial and non-microbial keratitis independently. METHODS: A cross-sectional study was conducted at Alexandria Ophthalmology Hospital from May to October 2023. All contact lens wearers attending the outpatient clinic had undergone face-to-face interviews using a standardized validated questionnaire which included demographic data and contact lenses (CLs) hygiene risk factors. Participants were classified into two groups; normal group and keratitis group. Keratitis group was further subdivided into non-microbial and microbial group. RESULTS: The study included 245 contact lens wearers; 149 normal cases, 50 (20.4%) contact lens-related non-microbial keratitis (CLNK) cases, and 46 (18.8%) contact lens-related microbial keratitis (CLMK) cases. Sharing contact lenses and eye trauma were significant risk factors for both CLNK (p=0.036), (p=0.001) and CLMK (p=0.003), (p=0.017). CLs wear duration for more than 12 hours was associated with an increased risk of CLNK by about 4 times (p=0.030) and overnight wear of contact lenses increased the risk of CLNK by 2.6 times (p=0.030). Showering or swimming in lenses was identified as a significant risk factor for CLMK (p=0.012), moreover washing lenses with tap water increased the risk of CLMK (p=0.030). CONCLUSIONS: Poor compliance with contact lenses hygiene rules results in a high prevalence of contact lens-related keratitis. Eye trauma and sharing contact lenses were significant hygiene risk factors for both contact lens-related non-microbial keratitis and contact lens-related microbial keratitis.

Intra- and Inter-Rater Reliability of Linear and Nonlinear Measures of Short-Term Heart Rate Variability Following Combat-Related Traumatic Injury.

BACKGROUND: Heart rate variability (HRV) is a marker of autonomic function. However, the reliability of short-term HRV measurement in individuals with combat-related traumatic injury (CRTI) remains undetermined. METHODS: An intra- and inter-rater reliability study was conducted using a subsample (n = 35) of British servicemen with CRTI enrolled in the ongoing ADVANCE study. A five-minute epoch of single-lead electrocardiogram data collected during spontaneous breathing was used to measure HRV. HRV analyses were independently performed by two examiners using Kubios. Intraclass correlation coefficient (ICC), standard error of measurement (SEM), minimum detectable change (MDC), and coefficient of variance were calculated for linear [root mean square of successive difference (RMSSD), standard deviation of NN interval, low-frequency, high-frequency, total power] and nonlinear (SD1-2, acceleration and deceleration capacities, sample entropy) measures. Bland-Altman %plots were used to assess bias in intra- and inter-rater HRV data. RESULTS: The mean age of participants was 39.3 ± 6.3 years. An excellent ICC score of 0.9998 (95% CI 0.9997, 0.9999) was observed for intra-rater analyses of RMSSD, and similar excellent ICC scores were seen for all other HRV measures. The inter-rater reliability analyses produced an excellent ICC score (range 0.97-1.00). Comparatively, frequency-domain measures produced higher MDC% and SEM% scores than time-domain and nonlinear measures in both inter- and intra-rater analyses. The Bland-Altman plots revealed relatively higher bias for frequency-domain and nonlinear measures than time-domain measures. CONCLUSION: ECG-related short-term HRV measures were reliable in injured servicemen under spontaneous breathing. However, the reliability appeared better with the time-domain measure than frequency-domain and nonlinear measures in this sample.

Validity of Ultra-Short-Term Heart Rate Variability Derived from Femoral Arterial Pulse Waveform in a British Military Cohort.

Various non-electrocardiogram (ECG) based methods are considered reliable sources of heart rate variability (HRV) measurement. However, the ultra-short recording of a femoral arterial waveform has never been validated against the gold-standard ECG-based 300s HRV and was the aim of this study.A validity study was conducted using a sample from the first follow-up of the longitudinal ADVANCE study UK. The participants were adult servicemen (n = 100); similar in age, rank, and deployment period (Afghanistan 2003-2014). The femoral arterial waveforms (14s) from the pulse wave velocity (PWV) assessment, and ECG (300s) were recorded at rest in the supine position using the Vicorder™ and Bittium Faros™ devices, respectively, in the same session. HRV analysis was performed using Kubios Premium. Resting heart rate (HR) and root mean square of successive differences (RMSSD) were reported. The Bland-Altman %plots were constructed to explore the PWV-ECG agreement in HRV measurement. A further exploratory analysis was conducted across methods and durations.The participants' mean age was 38.0 ± 5.3 years. Both PWV-derived HR (r = 0.85) and RMSSD (rs=0.84) showed strong correlations with their 300s-ECG counterparts (p < 0.001). Mean HR was significantly higher with ECG than PWV (mean bias: -12.71 ± 7.73%, 95%CI: -14.25%, -11.18%). In contrast, the difference in RMSSD between the two methods was non-significant [mean bias: -2.90 ± 37.82% (95%CI: -10.40%, 4.60%)] indicating good agreement. An exploratory analysis of 14s ECG-vs-300s ECG measurement revealed strong agreement in both RMSSD and HR.The 14s PWV-derived RMSSD strongly agrees with the gold-standard (300s-ECG-based) RMSSD at rest. Conversely, HR appears method sensitive.

AoUPRS: A Cost-Effective and Versatile PRS Calculator for the All of Us Program.

Background: The All of Us (AoU) Research Program provides a comprehensive genomic dataset to accelerate health research and medical breakthroughs. Despite its potential, researchers face significant challenges, including high costs and inefficiencies associated with data extraction and analysis. AoUPRS addresses these challenges by offering a versatile and cost-effective tool for calculating polygenic risk scores (PRS), enabling both experienced and novice researchers to leverage the AoU dataset for significant genomic discoveries. Results: AoUPRS is implemented in Python and utilizes the Hail framework for genomic data analysis. It offers two distinct approaches for PRS calculation: the Hail MatrixTable (MT) and the Hail Variant Dataset (VDS). The MT approach provides a dense representation of genotype data, while the VDS approach offers a sparse representation, significantly reducing computational costs. In performance evaluations, the VDS approach demonstrated a cost reduction of up to 99.51% for smaller scores and 85% for larger scores compared to the MT approach. Both approaches yielded similar predictive power, as shown by logistic regression analyses of PRS for coronary artery disease, atrial fibrillation, and type 2 diabetes. The empirical cumulative distribution functions (ECDFs) for PRS values further confirmed the consistency between the two methods. Conclusions: AoUPRS is a versatile and cost-effective tool that addresses the high costs and inefficiencies associated with PRS calculations using the AoU dataset. By offering both dense and sparse data processing approaches, AoUPRS allows researchers to choose the approach best suited to their needs, facilitating genomic discoveries. The tool's open-source availability on GitHub, coupled with detailed documentation and tutorials, ensures accessibility and ease of use for the scientific community.

Cardiovascular Autonomic Dysfunction in Hospitalized Patients with a Bacterial Infection: A Longitudinal Observational Pilot Study in the UK.

PURPOSE: A temporal reduction in the cardiovascular autonomic responses predisposes patients to cardiovascular instability after a viral infection and therefore increases the risk of associated complications. These findings have not been replicated in a bacterial infection. This pilot study will explore the prevalence of cardiovascular autonomic dysfunction (CAD) in hospitalized patients with a bacterial infection. METHODS: A longitudinal observational pilot study was conducted. Fifty participants were included: 13 and 37 participants in the infection group and healthy group, respectively. Recruitment and data collection were carried out during a two-year period. Participants were followed up for 6 weeks: all participants' cardiovascular function was assessed at baseline (week 1) and reassessed subsequently at week 6 so that the progression of the autonomic function could be evaluated over that period of time. The collected data were thereafter analyzed using STATA/SE version 16.1 (StataCorp). The Fisher Exact test, McNemar exact test, Mann-Whitney test and Wilcoxon test were used for data analysis. RESULTS: 32.4% of the participants in the healthy group were males (n = 12) and 67.6% were females (n = 25). Participants' age ranged from 33 years old to 76 years old with the majority being 40-60 years of age (62.1%) (Mean age 52.4 SD = 11.4). Heart rate variability (HRV) in response to Valsalva Maneuver, metronome breathing, standing and sustained handgrip in the infection group was lower than in the healthy group throughout the weeks. Moreover, both the HRV in response to metronome breathing and standing up showed a statistically significant difference when the mean values were compared between both groups in week 1 (p = 0.03 and p = 0.013). The prevalence of CAD was significantly higher in the infection group compared to healthy volunteers, both at the beginning of the study (p = 0.018) and at the end of follow up (p = 0.057), when all patients had been discharged. CONCLUSIONS: CAD, as assessed by the HRV, is a common finding during the recovery period of a bacterial infection, even after 6 weeks post-hospital admission. This may increase the risk of complications and cardiovascular instability. It may therefore be of value to conduct a wider scale study to further evaluate this aspect so recommendations can be made for the cardiovascular autonomic assessment of patients while they are recovering from a bacterial infectious process.

The relationship between ambulatory arterial stiffness index and incident atrial fibrillation.

BACKGROUND: The ambulatory arterial stiffness index (AASI) is an indirect measure of blood pressure variability and arterial stiffness which are atrial fibrillation (AF) risk factors. The relationship between AASI and AF development has not been previously investigated and was the primary aim of this study. METHODS: This was an observational cohort study of adults (aged 18-85 years) in sinus rhythm, who underwent 24-h ambulatory blood pressure monitoring (ABPM) for the diagnosis of hypertension or its control. RESULTS: Eight hundred and twenty-one patients (49% men) aged 58.7 ± 15.3 years were followed up for a median of 4.0 years (3317 patient-years). In total, 75 patients (9.1%) developed ≥1 AF episode during follow-up. The mean AASI was 0.46 ± 0.17 (median 0.46). AASI values (0.52 ± 0.16 vs. 0.45 ± 0.17; p < .001) and the proportion of AASI values above the median (65.3% vs. 48.4%; p = .005) were greater among the patients who developed AF versus those that did not respectively. AASI significantly correlated with age (r = .49; 95% confidence interval: 0.44-0.54: p < .001). On Kaplan-Meier analysis, higher baseline AASI by median, tertiles, and quartiles were all significantly associated with AF development (X2: 10.13; p < .001). On Cox regression analyses, both a 1-standard deviation increase and AASI > median were independent predictors of AF, but this relationship was no longer significant when age was included in the model. CONCLUSIONS: AASI is an independent predictor of AF development. However, this relationship becomes insignificant after adjustment for age which is higher correlated with AASI.

Exploratory analysis of spontaneous versus paced breathing on heart rate variability in veterans with combat-related traumatic injury.

BACKGROUND: Respiration is a crucial determinant of autonomic balance and heart rate variability (HRV). The comparative effect of spontaneous versus paced breathing on HRV has been almost exclusively explored in healthy adults and never been investigated in an injured military cohort. OBJECTIVE: To examine the effect of spontaneous versus paced breathing on HRV in veterans with combat-related traumatic injury (CRTI). DESIGN: Observational cohort study. SETTING: ArmeD serVices trAuma rehabilitatioN outComE (ADVANCE) study, Stanford Hall, UK. PARTICIPANTS: The sample consisted of 100 randomly selected participants who sustained CRTI (eg, amputation) during their deployment (Afghanistan 2003-2014) and were recruited into the ongoing ADVANCE prospective cohort study. INTERVENTION: Not applicable. MAIN OUTCOME MEASURE: HRV was recorded using a single-lead ECG. HRV data were acquired during a sequential protocol of 5-minute spontaneous breathing followed immediately by 5 minutes of paced breathing (six cycles/minute) among fully rested and supine participants. HRV was reported using time domain (root mean square of successive differences), frequency domain (low frequency and high frequency) and nonlinear (sample entropy) measures. The agreement between HRV during spontaneous versus paced breathing was examined using the Bland-Altman analysis. RESULTS: The mean age of participants was 36.5 ± 4.6 years. Resting respiratory rate was significantly higher with spontaneous versus paced breathing (13.4 ± 3.4 vs. 7.6 ± 2.0 breaths/minute; p < .001), respectively. Resting mean heart rate and root mean square of successive differences were significantly higher with paced breathing than spontaneous breathing (p < .001). Paced breathing significantly increased median low frequency power than spontaneous breathing (p < .001). No significant difference was found in the absolute power of high frequency between the two breathing protocols. The Bland-Altman analysis revealed poor agreement between HRV values during spontaneous and paced breathing conditions with wide limits of agreement. CONCLUSION: Slow-paced breathing leads to higher HRV than spontaneous breathing and could overestimate resting "natural-state" HRV.

Empagliflozin Reduces Liver Fat in Individuals With and Without Diabetes.

OBJECTIVE: To examine the effect of empagliflozin on liver fat content in individuals with and without type 2 diabetes (T2D) and the relationship between the decrease in liver fat and other metabolic actions of empagliflozin. RESEARCH DESIGN AND METHODS: Thirty individuals with T2D and 27 without were randomly assigned to receive in double-blind fashion empagliflozin or matching placebo (2:1 ratio) for 12 weeks. Participants underwent 75-g oral glucose tolerance testing and measurement of liver fat content with MRS before therapy and at study end. Hepatic glucose production before the start of therapy was measured with 3-3H-glucose. RESULTS: Empagliflozin caused an absolute reduction of 2.39% ± 0.79% in liver fat content compared with an increase of 0.91% ± 0.64% in participants receiving placebo (P < 0.007 with ANOVA). The decrease in liver fat was comparable in both individuals with diabetes and those without (2.75% ± 0.81% and 1.93% ± 0.78%, respectively; P = NS). The decrease in hepatic fat content caused by empagliflozin was strongly correlated with baseline liver fat content (r = -0.62; P < 0.001), decrease in body weight (r = 0.53; P < 0.001), and improvement in insulin sensitivity (r = -0.51; P < 0.001) but was not related to the decrease in fasting plasma glucose or HbA1c or the increase in hepatic glucose production. CONCLUSIONS: Empagliflozin is effective in reducing liver fat content in individuals with and without T2D. The decrease in liver fat content is independent of the decrease in plasma glucose concentration and is strongly related to the decrease in body weight and improvement in insulin sensitivity.

Ambulatory arterial stiffness index, mortality, and adverse cardiovascular outcomes; Systematic review and meta-analysis.

The ambulatory arterial stiffness index (AASI) is a novel measure of both blood pressure (BP) variability and arterial stiffness. This systematic review and meta-analysis was designed to evaluate the strength of the association between AASI and mortality and major adverse cardiovascular events (MACE). PubMed, Scopus, CINAHL, Google Scholar. and the Cochrane library were searched for relevant studies to July 31, 2023. Two investigators independently extracted data. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of all included articles. The relationship between baseline AASI and outcomes were examined using relative risk (RR) ratios with 95% confidence intervals (CI) with RevMan web. Thirteen studies were included and representing 28 855 adult patients who were followed up from 2.2 to 15.2 years. A 1-standard deviation (1-SD) increase in AASI was associated with a significant increase in all-cause death (RR 1.12; 95% CI: 0.95-1.32), stroke (RR 1.25; 95% CI: 1.09-1.44), and MACE (RR 1.07; 95% CI: 1.01-1.13; [I2  = 32%]). Higher dichotomized AASI (above vs. below researcher defined cut-offs) was associated with a significant increase in all-cause mortality (RR 1.19; 95% CI: 1.06-1.32), cardiovascular death (RR 1.29; 95% CI: 1.14-1.46), stroke (RR 1.57; 95% CI: 1.33-1.85), and MACE (RR1.29; 95% CI: 1.16-1.44). There was a significant risk of bias in more than 50% of studies with no evidence of significant publication bias. Higher AASI is associated with an increased risk of all-cause and cardiovascular death, stroke, and MACE. Further high-quality studies are warranted to determine reproducible AASI cut-offs to enhance its clinical risk precision.

The Influence of Physical and Mental Health Mediators on the Relationship Between Combat-Related Traumatic Injury and Ultra-Short-Term Heart Rate Variability in a U.K. Military Cohort: A Structural Equation Modeling Approach.

INTRODUCTION: Combat-related traumatic injury (CRTI) adversely affects heart rate variability (HRV). The mediating effect of mental and physical health factors on the relationship between CRTI, its severity and HRV has not been previously studied and investigated. MATERIALS AND METHODS: A cross-sectional mediation analysis of the ArmeD SerVices TrAuma and RehabilitatioN OutComE (ADVANCE) prospective cohort study was performed. The sample consisted of injured and uninjured British male servicemen who were frequency-matched based on their age, rank, role-in-theater, and deployment to Afghanistan (2003-2014). CRTI and injury severity (the New Injury Severity Scores [NISS] [NISS < 25 and NISS ≥ 25]) were included as exposure variables. HRV was quantified using the root mean square of successive differences (RMSSD) obtained using pulse waveform analysis. Depression and anxiety mediators were quantified using the Patient Health Questionnaire and Generalized Anxiety Disorder, respectively. Body mass index and the 6-minute walk test (6MWT) represented physical health measures. Two mediation pathways between exposure and outcome variables were examined in comparison with the uninjured group using structural equation modeling. RESULTS: Of 862 servicemen, 428 were injured and 434 were uninjured with the mean age at assessment of 33.9 ± 5.4 (range 23-59) years. Structural equation modeling revealed that depression, anxiety, and body mass index did not significantly mediate the relationship between injury/injury severity and RMSSD. However, the 6MWT significantly mediated the relationship between CRTI and RMSSD (27% mediation). The indirect effect of 6MWT on the relationship between injury severity (NISS ≥ 25 vs. uninjured) and RMSSD was -0.06 (95% CI: -0.12, -0.00, P < .05). CONCLUSIONS: The findings suggest that greater physical function may improve HRV following CRTI. Longitudinal studies are warranted to further validate these findings.

The impact of increased hepatic glucose production caused by empagliflozin on plasma glucose concentration in individuals with type 2 diabetes and nondiabetic individuals.

AIM: To examine the impact of increased hepatic glucose production (HGP) on the decrease in plasma glucose concentration caused by empagliflozin in individuals living with diabetes and in nondiabetic individuals. METHODS: A total of 36 individuals living with diabetes and 34 nondiabetic individuals were randomized to receive, in double-blind fashion, empagliflozin or matching placebo in a 2:1 treatment ratio. Following an overnight fast, HGP was measured with 3-3 H-glucose infusion before, at the start of, and 3 months after therapy with empagliflozin. RESULTS: On Day 1 of empagliflozin administration, the increase in urinary glucose excretion (UGE) in individuals with normal glucose tolerance was smaller than in those with impaired glucose tolerance and those living with diabetes, and was accompanied by an increase in HGP in all three groups. The amount of glucose returned to the systemic circulation as a result of the increase in HGP was smaller than that excreted by the kidney during the first 3 h after empagliflozin administration, resulting in a decrease in fasting plasma glucose (FPG) concentration. After 3 h, the increase in HGP was in excess of UGE, leading to a small increase in plasma glucose concentration, which reached a new steady state. After 12 weeks, the amount of glucose returned to the circulation due to the empagliflozin-induced increase in HGP was comparable with that excreted by the kidney in all three groups. CONCLUSION: The balance between UGE and increase in HGP immediately after sodium-glucose cotransporter-2 (SGLT2) inhibition determined the magnitude of decrease in FPG and the new steady state which was achieved. After 12 weeks, the increase in HGP caused by empagliflozin closely matched the amount of glucose excreted by the kidneys; thus, FPG level remained stable despite the continuous urinary excretion of glucose caused by SGLT2 inhibition.

A comprehensive overview of eco-friendly bio-fertilizers extracted from living organisms.

Currently, sustainable agriculture involves ecofriendly techniques, which include biofertilization. Biofertilizers increase plant productivity by improving soil fertility and nutrient content. A wide range of living organisms can be applied as biofertilizers and increase soil fertility without causing pollution due to their biodegradability. The organisms can be microorganisms like bacteria, microalgae, and micro fungi or macro organisms like macroalgae, macro fungi, and higher plants. Biofertilizers extracted from living organisms or their residues will be increasingly used rather than chemical fertilizers, which cause heavy metal accumulation in soil. Biofertilizer use aims for sustainable development in agriculture by maintaining the soil. This will mitigate climate change and related impacts and will also lower many serious diseases resulting from pollution such as cancer, liver and renal failure, and immune diseases. This review is a comprehensive overview of biofertilizers extracted from a range of living organisms from the Kingdoms Monera to Plantae and included bacteria, algae, fungi, and higher plants. Organisms that play a vital role in elevating soil nutrients in a safe, cheap, and ecofriendly manner are included in the review to promote their potential commercial application.

Inflammatory Cytokines Are Associated with Cognitive Dysfunction and Depressive State during Acute Bacterial Infections and the Recovery Phase.

During a bacterial infection, individuals may present with behavioral changes referred to as sickness behavior, which has been suggested is induced by the inflammatory markers that are released because of the infective immunological challenge. However, few studies have explored this multidimensional phenomenon in naturally occurring conditions. A longitudinal observational study was conducted to explore the role of inflammatory cytokines in mediating the sickness behavior during a bacterial infection. There were 13, 11 and 37 participants in the infection, hospital control and healthy groups, respectively. They were all followed up for 6 weeks and their inflammatory markers were quantified throughout those weeks. Cognitive function and depressive state were assessed by means of the Mini-Mental State Examination (MMSE) and Cornell Scale for Depression in Dementia (CSDD). Reductions in proinflammatory markers C-Reactive protein (CRP), interleukin - 6 (IL6) and tumor necrosis factor-α (TNFα) and increments in anti-inflammatory markers (interleukin - 4 (IL4)) were associated with an improvement in CSDD and MSEE in patients recovering from a bacterial infection. The correlation between inflammatory makers and CSDD was statistically significant for the CRP (r = 0.535, p = 0.001), the IL6 (r = 0.499, p < 0.001), the TNFα (r = 0.235, p = 0.007) and the IL4 (r = -0.321, p = 0.018). Inflammatory cytokines may mediate sickness behavior during acute illness. These results may enhance the understanding of the pathophysiology and potential treatment strategies to palliate this sickness behavior.

Reliability of carotid-femoral arterial waveforms for the derivation of ultra-short term heart rate variability in injured British servicemen: An inter-rater reliability study.

In this study, the comparative precision of carotid versus femoral arterial waveforms to measure ultra-short term heart rate variability (HRVUST) following traumatic injury was investigated for the first time. This was an inter-rater reliability study of 50 British servicemen (aged 23-44 years) with non-acute combat-related traumatic injury (CRTI). Paired continuous arterial waveform data for HRVUST analysis, were simultaneously sampled at the carotid and femoral arterial sites (14-16 seconds) during pulse wave velocity (PWV) measurement. HRVUST was reported as the root mean square of the successive differences (RMSSD). Following the determination of the superior sampling site (carotid versus femoral), the blinded inter-rater agreement in RMSSD for the preferred site was quantified using the Intra-class Correlation Coefficient (ICC) and the Bland-Altman plot. The mean age of participants was 34.06±4.88 years. The femoral site was superior to the carotid site with a significantly higher number of reliable signals obtained (Fisher's Exact test; p<0.001). The inter-rater agreement in femoral-derived RMSSD was excellent [ICC 0.99 (95%CI: 0.994-0.997)] with a moderate level of agreement (mean difference [bias]: 0.55; 95% CI: -0.13-1.24 ms). In this study, we demonstrated that the femoral artery is a more reliable site than the carotid artery for HRVUST measurement and post-trauma risk stratification following CRTI.

Donor Cell Leukemia Following Allogeneic Hematopoietic Stem Cell Transplantation.

Approximately 25,000 allogeneic transplants are performed annually worldwide; a figure that has steadily increased over the past three decades. The study of transplant recipient survivorship has become a cogent topic and post-transplant donor cell pathology warrants further study. Donor cell leukemia (DCL) is a rare but serious complication of allogeneic stem cell transplantation (SCT) where the recipient develops a form leukemia originating from the donor cells used for transplantation. Detection of abnormalities predicting donor cell pathology might inform donor selection, and the design of survivorship programs for early detection of these abnormalities might allow therapeutic intervention earlier in the disease course. We present four recipients of allogeneic hematopoietic stem cell transplant (HSCT) from our institution who developed donor cell abnormalities allogeneic SCT, highlighting their clinical characteristics and challenges.

Corticotropin releasing factor-1 receptor antagonism associated with favorable outcomes of male reproductive health biochemical parameters.

Background: Disruption in androgen profiles and testicular adrenal rest tumors in males with congenital adrenal hyperplasia (CAH) can negatively affect sexual activity and fertility. Adrenal hyperandrogenism suppresses gonadotropin secretion and testicular adrenal rest tumors (TARTS), despite being noncancerous lesions, cause obstructive azoospermia and impaired testosterone (T) production. Circulating T in men with uncontrolled CAH is often predominantly adrenal in origin, which is reflected in high androstenedione/testosterone ratios (A4/T). Therefore, decreased luteinizing hormone (LH) levels and an increased A4/T are markers of impaired fertility in these individuals. Methods: Oral tildacerfont 200 to 1000 mg once daily (QD) (n=10) or 100 to 200 mg twice daily (n=9 and 7) for 2 weeks (Study 201), and 400 mg QD (n=11) for 12 weeks (Study 202). Outcomes measured changes from baseline in A4, T, A4/T, and LH. Results: Mean T levels increased in Study 201 from 375.5 ng/dL to 390.5 ng/dL at week 2 (n=9), 485.4 ng/dL at week 4 (n=4) and 420.7 ng/dL at week 6 (n=4). In Study 202, T levels fluctuated in the normal range from 448.4 ng/dL at baseline to 412.0 ng/dL at week 12. Mean LH levels increased in Study 201 from 0.68 IU/L to 1.59 IU/L at week 2 (n=10), 1.62 IU/L at week 4 (n=5) and 0.85 IU/L at week 6 (n=4). In Study 202, mean LH levels increased from 0.44 IU/L at baseline to 0.87 IU/L at week 12. Mean A4/T decreased across both studies. In Study 201, the mean A4/T changed from a baseline of 1.28 to 0.59 at week 2 (n=9), 0.87 at week 4 (n=4), and 1.03 at week 6 (n=4). In Study 202, the A4/T decreased from baseline of 2.44 to 0.68 at week 12. Four men were hypogonadal at baseline; all experienced improved A4/T and 3/4 (75%) reached levels <1. Conclusion: Tildacerfont treatment demonstrated clinically meaningful reductions in A4 levels, and A4/T with concomitant increased LH levels indicating increased testicular T production. The data suggests improvement in hypothalamic-pituitary-gonadal axis function, but more data is required to confirm favorable male reproductive health outcomes.

Impacts of algae supplements (Arthrospira & Chlorella) on growth, nutrient variables, intestinal efficacy, and antioxidants in New Zealand white rabbits.

An 8-week trial to examine the impacts of Arthrospira platensis and Chlorella vulgaris on the growth, nutrient aspects, intestinal efficacy, and antioxidants of 75 New Zealand white male rabbits (initial body weight = 665.93 ± 15.18 g). Herein the study was designed in one-way ANOVA to compare the effects of the two algae species with two levels of supplementations in the feeds of New Zealand white rabbits. The rabbits were divided into five groups (n = 15/group), where the first group was allocated as the control group (Ctrl) while the second and third groups received A. platensis at 300 or 500 mg/kg diet (Ap300 or Ap500). The fourth and fifth groups fed C. vulgaris at 300 or 500 mg/kg diet (Ch300 or Ch500). The basal diet rabbits exhibited the lowest values of weight, lipase, protease, and the highest feed conversion ratio, which improved noticeably with algae addition, particularly with Ap500, Ch300, and Ch500. All tested groups showed normal intestinal structure. Amylase potency, hematological indicators, and serum biochemistry revealed non-significant variation except for a higher serum total protein and lower total cholesterol in algal groups. The best GPx existed in groups fed algal diets, while favorable SOD and CAT efficiency occurred at the higher level of Arthrospira and both levels of Chlorella. In conclusion, incorporating Arthrospira or Chlorella in the diet of New Zealand white rabbits improved performance, nutrient utilization, intestinal efficacy, and antioxidants. Arthrospira (Ap500) and Chlorella (Ch300 or Ch500) have almost the same beneficial effect on rabbit performance.

Distinct Mechanisms Responsible for the Increase in Glucose Production and Ketone Formation Caused by Empagliflozin in T2DM Patients.

OBJECTIVE: To examine the mechanisms responsible for the increase in glucose and ketone production caused by empagliflozin in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: Twelve subjects with T2DM participated in two studies performed in random order. In study 1, endogenous glucose production (EGP) was measured with 8-h infusion of 6,6,D2-glucose. Three hours after the start of 6,6,D2-glucose infusion, subjects ingested 25 mg empagliflozin (n = 8) or placebo (n = 4), and norepinephrine (NE) turnover was measured before and after empagliflozin ingestion with 3H-NE infusion. Study 2 was similar to study 1 but performed under pancreatic clamp conditions. RESULTS: When empagliflozin was ingested under fasting conditions, EGP increased by 31% in association with a decrease in plasma glucose (-34 mg/dL) and insulin (-52%) concentrations and increases in plasma glucagon (+19%), free fatty acid (FFA) (+29%), and ß-hydroxybutyrate (+48%) concentrations. When empagliflozin was ingested under pancreatic clamp conditions, plasma insulin and glucagon concentrations remained unchanged, and the increase in plasma FFA and ketone concentrations was completely blocked, while the increase in EGP persisted. Total-body NE turnover rate was greater in subjects receiving empagliflozin (+67%) compared with placebo under both fasting and pancreatic clamp conditions. No difference in plasma NE concentration was observed in either study. CONCLUSIONS: The decrease in plasma insulin and increase in plasma glucagon concentration caused by empagliflozin is responsible for the increase in plasma FFA concentration and ketone production. The increase in EGP caused by empagliflozin is independent of the change in plasma insulin or glucagon concentrations and is likely explained by the increase in NE turnover.

Association between non-acute Traumatic Injury (TI) and Heart Rate Variability (HRV) in adults: A systematic review and meta-analysis.

Heart rate variability (HRV) is a non-invasive measure of autonomic function. The relationship between unselected long-term traumatic injury (TI) and HRV has not been investigated. This systematic review examines the impact of non-acute TI (>7 days post-injury) on standard HRV indices in adults. Four electronic databases (CINAHL, Medline, Scopus, and Web of Science) were searched. The quality of studies, risk of bias (RoB), and quality of evidence (QoE) were assessed using Axis, RoBANS and GRADE, respectively. Using the random-effects model, mean difference (MD) for root mean square of successive differences (RMSSD) and standard deviation of NN-intervals (SDNN), and standardized mean difference (SMD) for Low-frequency (LF): High-Frequency (HF) were pooled in RevMan guided by the heterogeneity score (I2). 2152 records were screened followed by full-text retrieval of 72 studies. 31 studies were assessed on the inclusion and exclusion criteria. Only four studies met the inclusion criteria. Three studies demonstrated a high RoB (mean RoBANS score 14.5±3.31) with a low QoE. TI was associated with a significantly higher resting heart rate. Meta-analysis of three cross-sectional studies demonstrated a statistically significant reduction in RMSSD (MD -8.45ms, 95%CI-12.78, -4.12, p<0.0001) and SDNN (MD -9.93ms, 95%CI-14.82, -5.03, p<0.0001) (low QoE) in participants with TI relative to the uninjured control. The pooled analysis of four studies showed a higher LF: HF ratio among injured versus uninjured (SMD 0.20, 95%CI 0.01-0.39, p<0.04) (very low QoE). Albeit low QoE, non-acute TI is associated with attenuated HRV indicating autonomic imbalance. The findings might explain greater cardiovascular risk following TI. Trial registration PROSPERO registration number: CRD: CRD42021298530.

Brentuximab-Induced Colitis in a Non-Stem-Cell Transplant Patient.

Many chemotherapeutic agents have been associated with drug-induced colitis (DIC). With newer agents' expansion of approval as first-line therapy for common cancers, it is important to be cognizant of their association with DIC. We present a case of brentuximab-associated DIC in an elderly woman with CD30+ Hodgkin lymphoma. Brentuximab's association with DIC was suspected by others in the literature, but a history of stem-cell transplant in them would blur the association with graft-vs-host disease. Lack of stem-cell transplant in our patient makes the link between brentuximab and DIC unambiguous.