Adolescent Body Mass Index and Early Chronic Kidney Disease in Young Adulthood.

Importance: Despite increasing obesity rates in adolescents, data regarding early kidney sequelae are lacking. Objective: To assess the association between adolescent body mass index (BMI) and early chronic kidney disease (CKD) in young adulthood (<45 years of age). Design, Setting, and Participants: This cohort study linked screening data of mandatory medical assessments of Israeli adolescents to data from a CKD registry of a national health care system. Adolescents who were aged 16 to 20 years; born since January 1, 1975; medically evaluated for mandatory military service through December 31, 2019; and insured by Maccabi Healthcare Services were assessed. Individuals with kidney pathology, albuminuria, hypertension, dysglycemia, or missing blood pressure or BMI data were excluded. Body mass index was calculated as weight in kilograms divided by height in meters squared and categorized by age- and sex-matched percentiles according to the US Centers for Disease Control and Prevention. Follow-up started at the time of medical evaluation or January 1, 2000 (whichever came last), and ended at early CKD onset, death, the last day insured, or August 23, 2020 (whichever came first). Data analysis was performed from December 19, 2021, to September 11, 2023. Main Outcomes and Measures: Early CKD, defined as stage 1 to 2 CKD by moderately or severely increased albuminuria, with an estimated glomerular filtration rate of 60 mL/min/1.73 m2 or higher. Results: Of 629 168 adolescents evaluated, 593 660 (mean [SD] age at study entry, 17.2 [0.5] years; 323 293 [54.5%] male, 270 367 [45.5%] female) were included in the analysis. During a mean (SD) follow-up of 13.4 (5.5) years for males and 13.4 (5.6) years for females, 1963 adolescents (0.3%) developed early CKD. Among males, the adjusted hazard ratios were 1.8 (95% CI, 1.5-2.2) for adolescents with high-normal BMI, 4.0 (95% CI, 3.3-5.0) for those with overweight, 6.7 (95% CI, 5.4-8.4) for those with mild obesity, and 9.4 (95% CI, 6.6-13.5) for those with severe obesity. Among females, the hazard ratios were 1.4 (95% CI, 1.2-1.6) for those with high-normal BMI, 2.3 (95% CI, 1.9-2.8) for those with overweight, 2.7 (95% CI, 2.1-3.6) for those with mild obesity, and 4.3 (95% CI, 2.8-6.5) for those with severe obesity. The results were similar when the cohort was limited to individuals who were seemingly healthy as adolescents, individuals surveyed up to 30 years of age, or those free of diabetes and hypertension at the end of the follow-up. Conclusions and Relevance: In this cohort study, high BMI in late adolescence was associated with early CKD in young adulthood. The risk was also present in seemingly healthy individuals with high-normal BMI and before 30 years of age, and a greater risk was seen among those with severe obesity. These findings underscore the importance of mitigating adolescent obesity rates and managing risk factors for kidney disease in adolescents with high BMI.

Dihydroxyphenylacetaldehyde Lowering Treatment Improves Locomotor and Neurochemical Abnormalities in the Rat Rotenone Model: Relevance to the Catecholaldehyde Hypothesis for the Pathogenesis of Parkinson's Disease.

The catecholaldehyde hypothesis for the pathogenesis of Parkinson's disease centers on accumulation of 3,4-dihydroxyphenylacetaldehyde (DOPAL) in dopaminergic neurons. To test the hypothesis, it is necessary to reduce DOPAL and assess if this improves locomotor abnormalities. Systemic administration of rotenone to rats reproduces the motor and central neurochemical abnormalities characterizing Parkinson's disease. In this study, we used the monoamine oxidase inhibitor (MAOI) deprenyl to decrease DOPAL production, with or without the antioxidant N-acetylcysteine (NAC). Adult rats received subcutaneous vehicle, rotenone (2 mg/kg/day via a minipump), or rotenone with deprenyl (5 mg/kg/day i.p.) with or without oral NAC (1 mg/kg/day) for 28 days. Motor function tests included measures of open field activity and rearing. Striatal tissue was assayed for contents of dopamine, DOPAL, and other catechols. Compared to vehicle, rotenone reduced locomotor activity (distance, velocity and rearing); increased tissue DOPAL; and decreased dopamine concentrations and inhibited vesicular sequestration of cytoplasmic dopamine and enzymatic breakdown of cytoplasmic DOPAL by aldehyde dehydrogenase (ALDH), as indicated by DA/DOPAL and DOPAC/DOPAL ratios. The addition of deprenyl to rotenone improved all the locomotor indices, increased dopamine and decreased DOPAL contents, and corrected the rotenone-induced vesicular uptake and ALDH abnormalities. The beneficial effects were augmented when NAC was added to deprenyl. Rotenone evokes locomotor and striatal neurochemical abnormalities found in Parkinson's disease, including DOPAL buildup. Administration of an MAOI attenuates these abnormalities, and NAC augments the beneficial effects. The results indicate a pathogenic role of DOPAL in the rotenone model and suggest that treatment with MAOI+NAC might be beneficial for Parkinson's disease treatment.

Risk factors for injuries along an infantry commanders course.

To determine the influence of prevention programme on somatosensory ability in combat soldiers during 14-weeks of an infantry commanders course, two cohorts were recruited (INT-group, n = 196; CONT-group, n = 169). Soldiers were tested pre-and post-course for anthropometric measurements, proprioceptive ability, dynamic postural balance, and filled CAIT questionnaire. The INT-group performed injury prevention exercises and the CONT-group continued with their routine physical fitness lessons. All musculoskeletal injuries were recorded along the course. In the CONT-group 24.2% and in the INT-group 19.9% suffered injury during the course. The rates of injuries were not significantly different between groups (χ2(1) = .677 p = .411). Previous injury (OR = 3.349, 95% CI = 1.283-8.740), pre-course BMI (OR = 1.216, 95% CI = 1.064-1.389), and pre-course proprioception ability (OR = .870, 95% CI = .810-.935) were factors associated with injury in the CONT-group. Pre-course proprioception ability (OR = .769, 95% CI = .699-.846) and pre-course CAIT score (OR = .087, 95% CI = .027-.276) were factors in the INT-group. Soldiers who received injury prevention exercises had a similar prevalence of total musculoskeletal injuries as those who did not receive these exercises. Risk factors for injuries were different in the two groups.

Venous thromboembolism among physically active young adult females.

Background: Young adult females are at risk of venous thromboembolism (VTE) due to various acquired and transient factors. In recent years, a growing number of females have engaged in strenuous physical activity, but its role as a risk factor for VTE is uncertain. Objectives: To determine the incidence of VTE in young adult females engaged in strenuous physical activity. Methods: A large national cohort of female individuals enlisted in the Israeli Defense Forces between 2012 and 2019 was analyzed. The study group consisted of participants undergoing strenuous physical training during their military service, while the control group maintained regular activity levels. We compared the incidence of VTE between the groups and adjusted for potential risk factors using a multivariate Cox analysis. Results: The cohort included 160,718 female individuals aged 18 to 21years, of whom 11,745 engaged in strenuous physical activity and 148,973 served as controls. During a mean follow-up of 1.7 years, VTE occurred in 5 individuals (0.04%) in the strenuous activity group and 47 individuals (0.03%) in the control group. The incidence per 10,000 person-years was 2.41 (95% CI, 0.78-5.62) for the strenuous activity group and 1.82 (95% CI, 1.34-2.42) for the controls. Strenuous activity did not increase the risk for VTE in univariate or multivariate regression, with a hazard ratio (HR) of 1.27 (95% CI, 0.49-4.22). Use of oral contraceptives was the only significant risk factor, demonstrating dose effect; HR 1.95 (95% CI, 1.06-3.57) for low dose and HR 3.62 (95% CI, 1.40-9.37) for medium estrogen dose contraceptives. Conclusion: Strenuous physical activity did not increase the risk for VTE among a large cohort of young adult female individuals.

The Use of Brain Natriuretic Peptide as a Decision-supporting Tool in Hospitalized Patients.

BACKGROUND: Most dyspneic patients in internal medicine departments have co-morbidities that interfere with the clinical diagnosis. The role of brain natriuretic peptide (BNP) levels is well-established in the acute setting but not in hospitalized patients. OBJECTIVES: To evaluate the additive value of BNP tests in patients with dyspnea admitted to medical wards who did not respond to initial treatment. METHODS: We searched the records of patients who were hospitalized in the department of internal medicine D at Sheba Medical Center during 2012 and were tested for BNP in the ward. Data collected included co-morbidity, medical treatments, diagnosis at presentation and discharge, lab results including BNP, re-hospitalization, and mortality at one year following hospitalization. RESULTS: BNP results were found for 169 patients. BNP was taken 1.7 ± 2.7 days after hospitalization. According to BNP levels, dividing the patients into tertiles revealed three equally distributed groups with a distinctive character. The higher tertile was associated with higher rates of cardiac co-morbidities, including heart failure, but not chronic obstructive pulmonary disease. Higher BNP levels were related to one-year re-hospitalization and mortality. In addition, higher BNP levels were associated with higher rates of in-admission diagnosis change. CONCLUSIONS: BNP levels during hospitalization in internal medicine wards are significantly related to cardiac illness, the existence of heart failure, and patient prognosis. Thus, BNP can be a useful tool in managing dyspneic patients in this setting.

Early detection of COVID-19 outbreaks using textual analysis of electronic medical records.

PURPOSE: Our objective was to develop a tool promoting early detection of COVID-19 cases by focusing epidemiological investigations and PCR examinations during a period of limited testing capabilities. METHODS: We developed an algorithm for analyzing medical records recorded by healthcare providers in the Israeli Defense Forces. The algorithm utilized textual analysis to detect patients presenting with suspicious symptoms and was tested among 92 randomly selected units. Detection of a potential cluster of patients in a unit prompted a focused epidemiological investigation aided by data provided by the algorithm. RESULTS: During a month of follow up, the algorithm has flagged 17 of the units for investigation. The subsequent epidemiological investigations led to the testing of 78 persons and the detection of eight cases in four clusters that were previously gone unnoticed. The resulting positive test rate of 10.25% was five time higher than the IDF average at the time of the study. No cases of COVID-19 in the examined units were missed by the algorithm. CONCLUSIONS: This study depicts the successful development and large scale deployment of a textual analysis based algorithm for early detection of COVID-19 cases, demonstrating the potential of natural language processing of medical text as a tool for promoting public health.

The rat rotenone model reproduces the abnormal pattern of central catecholamine metabolism found in Parkinson's disease.

Recent reports indicate that Parkinson's disease (PD) involves specific functional abnormalities in residual neurons - decreased vesicular sequestration of cytoplasmic catecholamines via the vesicular monoamine transporter (VMAT) and decreased aldehyde dehydrogenase (ALDH) activity. This double hit builds up the autotoxic metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), the focus of the catecholaldehyde hypothesis for the pathogenesis of PD. An animal model is needed that reproduces this abnormal catecholamine neurochemical pattern. Adult rats received subcutaneous vehicle or the mitochondrial complex 1 inhibitor rotenone (2 mg/kg/day via a minipump) for 10 days. Locomotor activity was recorded, and striatal tissue sampled for catechol contents and catechol ratios that indicate the above abnormalities. Compared to vehicle, rotenone reduced locomotor activity (P=0.002), decreased tissue dopamine concentrations (P=0.00001), reduced indices of vesicular sequestration (3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine) and ALDH activity (DOPAC/DOPAL) (P=0.0025, P=0.036), and increased DOPAL levels (P=0.04). The rat rotenone model involves functional abnormalities in catecholaminergic neurons that replicate the pattern found in PD putamen. These include a vesicular storage defect, decreased ALDH activity and DOPAL build-up. The rat rotenone model provides a suitable in vivo platform for studying the catecholaldehyde hypothesis.

Young Adults with Mild Asthma in a High-Risk Occupation: Incidence and Risk Factors for Exacerbation.

BACKGROUND: The effects of high-risk environment on young adults with mild asthma were never fully tested in practice, as most high-risk occupations do not welcome them. This study examines the effect of combat training on asthma worsening in the Israeli Defense Forces. METHODS: Persons with asthma in remission and mild intermittent asthma who underwent combat training between 2014 and 2017 were compared in terms of disease worsening to their counterparts performing clerical duties during a follow-up of 8 months. Among combat trainees, exposure to known triggers for asthma exacerbation and health status on enlistment were assessed as risk factors for asthma exacerbation. RESULTS: Asthma worsening among persons with asthma in remission was twice as common among those who are undergoing training compared to persons performing clerical duties. This difference was smaller among mild intermittent asthmatics. For both asthma severities, rates of asthma exacerbation requiring emergency room treatment were several times higher among the training group. Among individuals undergoing training, mild intermittent asthma was a significant risk factor for asthma worsening compared to asthma in remission (OR 1.99 [1.44-2.75]) while age (OR 0.67 [0.53-0.85]) and immigration to Israel (OR 0.55 [0.31-0.95]) were significant protective factors. INTERPRETATION: Young adults with mild asthma are at significant risk for severe exacerbations when exposed to high-risk environment even among individuals who have long been symptom free. No single risk factor was found to have an independent effect suggesting a synergistic mechanism that is harder to mitigate.

Medial tibial stress fracture diagnosis and treatment guidelines.

OBJECTIVES: To validate and make evidence based changes to the Israel Defense Forces medial tibial stress fracture diagnosis and treatment protocol. DESIGN: Prospective cohort study. METHODS: 429 Elite infantry recruits were reviewed for signs and symptoms of medial tibial stress fracture during 14 weeks of basic training. Suspicion of medial tibial stress fracture was based on the presence of pain, tenderness <1/3 the length of the tibia and a positive fulcrum and/or hop test. Recruits with suspected medial tibial stress fractures were initially treated with 10-14 days of rest. Bone scan was performed only when recruits failed to respond to the rest regimen or required immediate diagnosis. RESULTS: 31 Out of 49 recruits with a suspicion of medial tibial stress fracture underwent bone scan, including 8/26 recruits whose symptoms did not resolve after being treated clinically as stress fractures. There was a significantly greater incidence of medial tibial stress fractures when a positive hop test was present in addition to tibial pain and tenderness (p=0.0001), odds ratio 52.04 (95% CL, 2.80-967.74). Medial tibial stress fracture was found to occur when the band of tibial tenderness was ≤10cm in length. Tibial pain scores were not predictive of stress fracture. CONCLUSIONS: This validation study provides the clinician with evidence based guidelines for the clinical diagnosis and treatment of medial stress fractures and their differentiation from shin splints. An initial treatment protocol without the use of imaging was found to be effective in more than two-thirds of the cases.

Ethnic Variability Among Jews is Associated With Hypertension: Results of a Nationwide Study of 1.44 Million Adolescents.

BACKGROUND: Adolescent hypertension is a major cardiovascular risk factor that may be related to ethnic variability. Contemporary Jews can be divided into three distinct ethnic groups: Ashkenazi, Oriental, and Sephardi origins. The aim of our study was to investigate the association of ethnicity and hypertension among Israeli adolescents. METHODS: We conducted a population retrospective cohort study of males and females, aged 16-19, eligible for mandatory military service in the Israeli Defense Forces (IDF) between 1994 and 2013. Medical and sociodemographic data, including body mass index (BMI), age, years of education, residential socioeconomic status, and parents' country of birth, were retrieved. Ethnicity of the parents was based upon their country of birth. The examinees were assigned to a certain ethnicity only if both parents had the same ethnicity. Logistic regression models were applied to compute the odds ratio (OR) and 95% confidence intervals (95% CI) for hypertension among the different Jewish ethnicities. RESULTS: The final cohort included 1,445,176 adolescents, of whom 716,289 were born to parents of the same Jewish ethnicity. Ashkenazi ethnicity was associated with an increased risk of hypertension compared to Sephardi and Oriental ethnicities (adjusted OR of 2.93 (95% CI, 2.52-3.41) and 1.56 (1.38-1.77), respectively). Oriental ethnicity was associated with an increased risk of hypertension compared with the Sephardi ethnicity (OR of 1.91 (1.60-2.27)). Similar results were observed in a sub-analysis, which included only Israeli-born examinees. CONCLUSIONS: Our results indicate that ethnicity is significantly associated with hypertension among Jewish adolescents. Ashkenazi Jews had the highest risk of hypertension.