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Background: Chronic kidney disease (CKD) is a major global health concern with increasing prevalence and associated complications. Obesity and obesity-related metabolic disorders have been linked to chronic kidney disease (CKD), although the evidence is still inconsistent. To investigate the relationship between different obesity phenotypes and the risk of CKD, we conducted a systematic review and meta-analysis., Method: We conducted a comprehensive search of databases for all relevant studies up to February 2024, without imposing a specific start date, for observational studies assessing the relationship between obesity phenotypes and incident kidney dysfunction. We used fixed and random effects models for the meta-analysis, subgroup analyses were carried out to explore heterogeneity, and Egger's and Begg's tests were used to assess publication bias., Result: This meta-analysis included 13 eligible observational studies with 492,829 participants. Pooling the studies regardless of the effect measure showed that individuals with metabolically unhealthy normal weight (MUNW) (ES = 1.58, 95% CI = 1.43-1.76), metabolically healthy obese (MHO) (ES = 1.20, 95% CI = 1.06-1.34), and metabolically unhealthy obese (MUO) (ES = 1.90, 95% CI = 1.63-2.20) phenotypes had a significantly increased risk for kidney dysfunction (KD) events. On the other hand, MUOW individuals did not significantly correlate with risk of CKD (ES = 1.63, 95% CI = 0.97-2.23) compared to the MHNW phenotype., Conclusion: Healthy overweight and obese individuals had higher risk for the incident KD events; refuting the notion that metabolically healthy overweight and obese phenotypes are benign conditions., Level of Evidence: III Evidence obtained from well-designed cohort or cross-sectional studies., (© 2024. The Author(s).)

Background: Childhood and adolescent obesity pose significant challenges to global health, with escalating prevalence and associated short- and long-term health consequences. This longitudinal study leveraged data from the Tehran Lipid and Glucose Study (TLGS) to investigate the trends of obesity among Tehranian children and adolescents over a 21-year period., Methods: Utilizing data from TLGS phases I to VII (1999-2021), we included 3845 participants aged 3-18 years at the beginning of phase I. Anthropometric measures, including height and weight, were collected, and body mass index (BMI) was calculated. Childhood obesity (2-19 years) was defined as BMI-for-age > 2SD based on World Health Organization (WHO) standards, and adult obesity was defined as BMI ≥ 30. Descriptive statistics, trend analysis, prevalence calculations, odds ratios, and interaction analyses were employed for data interpretation., Results: The mean BMI increased from 18.46 ± 4.37 kg/m² at Phase I to 26.36 ± 5.03 kg/m² at Phase VII. Boys exhibited a greater increase in BMI than girls, and age at study entry influenced BMI trajectories. The prevalence of obesity rose from 6.4% at Phase I to 21.5% at Phase VII, with a more pronounced increase in boys. Odds ratios for obesity steadily increased across phases, indicating a growing risk. Interaction analyses revealed age-specific dynamics, with older participants demonstrating lower odds ratios initially but higher odds ratios in later phases., Conclusion: Our study shows a worrisome increase in childhood obesity among Tehranian children and adolescents over 21 years. Sex- and age-specific trends emphasize the necessity for targeted interventions, informing policymakers, healthcare practitioners, and educators regarding public health strategies and interventions against the obesity epidemic., (© 2024. The Author(s).)

The complicated relevance between stress and pain has been identified. Neurotransmitters and neuropeptides of various brain areas play a role in this communication. Pain inhibitory response is known as stress-induced analgesia (SIA). The studies demonstrated that the nucleus accumbens (NAc) is critical in modulating pain. As a neuropeptide, orexin is crucially involved in initiating behavioral and physiological responses to threatening and unfeeling stimuli. However, the role of the orexin receptors of the NAc area after exposure to restraint stress (RS) as acute physical stress in the modulation of acute pain is unclear. One hundered twenty adult male albino Wistar rats (230-250 g) were used. Animals were unilaterally implanted with cannulae above the NAc. The SB334867 and TCS OX2 29 were used as antagonists for OX1r and OX2r, respectively. Different doses of the antagonists (1, 3, 10, and 30 nmol/0.5 µl DMSO) were microinjected intra-NAc five minutes before exposure to RS (3 hours). Then, the tail-flick test as a model of acute pain was performed, and the nociceptive threshold (Tail-flick latency; TFL) was measured in 60-minute time set intervals. According to this study's findings, the antinociceptive effects of RS in the tail-flick test were blocked during intra-NAc administration of SB334867 or TCS OX2 29. The RS as acute stress increased TFL and deceased pain-like behavior responses. The 50 % effective dose values of the OX1r and OX2r antagonists were 12.82 and 21.64 nmol, respectively. The result demonstrated contribution of the OX1r into the NAc was more remarkable than that of the OX2r on antinociceptive responses induced by the RS. Besides, in the absence of RS, the TFL was attenuated. The current study's data indicated that OX1r and OX2r into the NAc induced pain modulation responses during RS in acute pain. In conclusion, the findings revealed the involvement of intra-NAc orexin receptors in improving SIA., Competing Interests: Declaration of Competing Interest The authors have no financial or non-financial interests to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Cushing's syndrome (CS) poses diagnostic challenges, particularly in distinguishing pituitary-dependent Cushing's syndrome, Cushing's disease (CD), from the ectopic ACTH syndrome (EAS). This study evaluated the diagnostic value of the desmopressin stimulation test (DST) in patients with ACTH-dependent CS in helping this discrimination., Methods: Twenty-three ACTH-dependent CS patients underwent sequential DST, bilateral inferior petrosal sinus sampling (BIPSS), and transsphenoidal surgery (TSS). Two definitions of a positive DST results were applied. Diagnostic performance was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios. To avoid bias from predetermined criteria, we generated univariate receiver-operating characteristic (ROC) curves, plotting sensitivity against 1-specificity at various percentage cortisol and ACTH response levels., Results: Against BIPSS, DST demonstrated robust sensitivity (Definition 1: 90.0%, Definition 2: 76.2%) and overall accuracy (Definition 1: 87.0%, Definition 2: 73.9%). PPV was high (Definition 1: 95.0%, Definition 2: 94.1%), but NPV indicated potential false negatives. Compared to TSS, DST showed good sensitivity (Definition 1: 90.9-77.3%) and PPV (100.0%) but limited NPV (16.7%). The likelihood ratios emphasized the diagnostic value of the test. Notably, against TSS, DST showed perfect discriminatory power (AUC 1.000 for percent ACTH, 0.983 for percent cortisol)., Conclusion: The desmopressin test shows promise in accurately identifying the underlying cause of ACTH-dependent CS, potentially reducing the reliance on invasive procedures and providing a practical solution for managing complex cases. Further research with larger cohorts is required to validate the utility of the DST in routine clinical practice.

Objectives: The global population is undergoing rapid aging, and the consequential decline in skeletal muscle mass with age presents substantial health risks, underscoring the importance of precise identification and gender-specific measurements. This study aimed to investigate the prevalence of low muscle mass among individuals aged > 60 years and identifying potential risk factors., Methods: This study, conducted within the framework of Phase VII of the Tehran Lipid and Glucose Study (TLGS), included 860 participants selected through meticulous inclusion and exclusion criteria, focusing on good health. Various demographic, anthropometric, and metabolic measurements were collected, and bioelectrical impedance analysis (BIA) was employed for skeletal muscle mass assessment. Multiple logistic regression analysis was conducted to evaluate associations between low muscle mass and various factors., Results: The prevalence of low skeletal muscle mass was 16.4% (CI: 14.06-19.03), with gender-based variations (20.24% (CI: 16.66-24.36) in males vs. 12.73% (CI: 9.92-16.19) in females). Multiple logistic regression analysis revealed associations between low muscle mass and increasing age, male gender, smoking, low physical activity, and higher HDL levels ( P  < 0.05). Protective effects were observed with higher BMI, weight, height, waist and hip circumference, and serum triglyceride levels ( P  < 0.05)., Conclusion: This study provides valuable insights into the prevalence and related factors of low skeletal muscle mass among older adults. Addressing modifiable risk factors and promoting healthy lifestyle behaviors are crucial steps in preventing and managing sarcopenia. Further longitudinal research is recommended to explore causal pathways and inform targeted interventions for optimizing muscle health across the lifespan., Competing Interests: Competing interestsNone., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Stress and pain are interleaved at numerous levels - influencing each other. Stress can increase the nociception threshold in animals, long-known as stress-induced analgesia (SIA). Orexin is known as a neuropeptide that modulates pain. The effect of stress on the mesolimbic system in the modulation of pain is known. The role of the intra-accumbal orexin receptors in the modulation of acute pain by forced swim stress (FSS) is unclear. In this study, 117 adult male albino Wistar rats (270-300 g) were used. The animals were unilaterally implanted with cannulae above the NAc. The antagonist of the orexin-1 receptor (OX1r), SB334867, and antagonist of the orexin-2 receptor (OX2r), TCS OX2 29, were microinjected into the NAc in different doses (1, 3, 10, and 30 nmol/0.5 µl DMSO) before exposure to FSS for a 6-min period. The tail-flick test was carried out as an assay nociception of acute pain, and the nociceptive threshold [tail-flick latency (TFL)] was measured for 60-minute. The findings demonstrated that exposure to acute stress could remarkably increase the TFLs and antinociceptive responses. Moreover, intra-accumbal microinjection of SB334867 or TCS OX2 29 blocked the antinociceptive effect of stress in the tail-flick test. The contribution of orexin receptors was almost equally modulating SIA. The present study's findings suggest that OX1r and OX2r within the NAc modulate stress-induced antinociceptive responses. The intra-accumbal microinjection of orexin receptors antagonists declares inducing antinociceptive responses by FSS in acute pain. Proposedly, intra-accumbla orexinergic receptors have a role in the development of SIA., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Fragmented QRS (fQRS), which is associated with rhythm disturbances, can predispose the heart to fatal ventricular arrhythmias. Recently, accumulating studies indicates that fQRS is associated with poor prognosis in various types of cardiomyopathies. Therefore, we assessed the association between fQRS with all-cause mortality and major arrhythmic events (MAEs) in patients with nonischemic cardiomyopathy, in this systematic review and meta-analysis study., Methods: We performed a comprehensive search in databases of PubMed/Medline, EMBASE, and Web of Science from the beginning to December 31, 2022. Published observational studies (cohorts, case-control, or analytical cross-sectional studies) were included that report the prognostic value of fQRS in patients with different types of nonischemic cardiomyopathies for MAEs (sudden cardiac death, sudden cardiac arrest, sustained ventricular tachycardia [VT], ventricular fibrillation [VF], and appropriate shock) and all-cause mortality. We pooled risk ratios (RRs) through raw data and adjusted hazard ratios (aHRs) using "Comprehensive Meta-Analysis" software, Version 2.0., Results: Nineteen cohort and three analytical cross-sectional studies were included in this meta-analysis involving a total of 4318 subjects with nonischemic cardiomyopathy (1279 with fQRS and 3039 without fQRS). FQRS was significantly associated with an increased risk of all-cause mortality in patients with nonischemic cardiomyopathy (pooled RR: 1.920; 95% confidence interval [CI]: 1.388-2.656, p  < 0.0001/pooled HR: 1.729; 95% CI: 1.327-2.251, p  < 0.0001). Also, the risk of developing MAEs in the presence of fQRS was significantly increased (pooled RR: 2.041; 95% CI: 1.644-2.533, p  < 0.0001/pooled HR: 3.626; 95% CI: 2.119-6.204, p  < 0.0001). In the subgroup analysis, the strongest association between fQRS presence and increased MAEs was observed in patients with hypertrophic cardiomyopathy (HCM) (pooled RR: 3.44; 95% CI: 2.07-5.71, p  < 0.0001/pooled HR: 3.21; 95% CI: 2.04-5.06, p  < 0.0001)., Conclusion: Fragmented QRS could be a prognostic marker for all-cause mortality and MAEs in patients with various types of nonischemic cardiomyopathies, particularly HCM., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Objectives: It has not been established whether vitamin D deficiency is associated with anthropometric state; therefore, this systematic review examined the relationship between serum vitamin D levels with anthropometrics and adiposity across different ages., Methods: Studies that examined vitamin D deficiency with adiposity measures in different age groups were searched in the PubMed, Scopus, Embase, and Google Scholar databases until November 2023. Two investigators independently reviewed titles and abstracts, examined full-text articles, extracted data, and rated the quality in accordance with the Newcastle-Ottawa criteria., Results: Seventy-two studies, with a total of 59,430 subjects, were included. Of these studies, 27 cross-sectional studies and one longitudinal study (with 25,615 participants) evaluated the possible link between 25(OH)D serum concentrations and anthropometric/adiposity indices in the pediatric population. Forty-two cross-sectional studies and two cohort investigations (with 33,815 participants) investigated the relationship between serum 25(OH)D levels and adiposity measures in adults and/or the elderly population. There is evidence supporting links between vitamin D deficiency and obesity, and revealed an inverse association between vitamin D and adiposity indicators, specifically in female subjects. However, the effects of several confounding factors should also be considered., Conclusion: Most published studies, most of which were cross-sectional, reported a negative association between vitamin D and female adiposity indicators. Therefore, serum vitamin D levels should be monitored in overweight/obese individuals.

Background: Chronic kidney disease (CKD) is a major global health concern with increasing prevalence and associated complications. Metabolic syndrome (MetS) has been linked to CKD, but the evidence remains inconsistent. We conducted a systematic review and meta-analysis to investigate the association between MetS and kidney dysfunction., Method: We conducted a comprehensive search of databases until December 2022 for cohort studies assessing the association between MetS and incident kidney dysfunction. Meta-analysis was performed using fixed and random effects models. Subgroup analyses were conducted to explore heterogeneity. Publication bias was assessed using Egger's and Begg's tests., Result: A total of 24 eligible studies, involving 6,573,911 participants, were included in this meta-analysis. MetS was significantly associated with an increased risk of developing CKD (OR, 1.42; 95% CI, 1.28, 1.57), albuminuria or proteinuria (OR, 1.43; 95% CI, 1.10, 1.86), and rapid decline in kidney function (OR, 1.25; 95% CI, 1.07, 1.47). Subgroup analyses showed a stronger association as the number of MetS components increased. However, gender-specific subgroups demonstrated varying associations., Conclusion: Metabolic syndrome is a significant risk factor for kidney dysfunction, requiring close renal monitoring. Lifestyle changes and targeted interventions may help reduce CKD burden. Further research is needed to understand the connection fully and assess intervention efficacy., Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01348-5., Competing Interests: Competing interestsNone., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Stress suppresses the sense of pain, a physiological phenomenon known as stress-induced analgesia (SIA). Brain orexin peptides regulate many physiological functions, including wakefulness and nociception. The contribution of the orexinergic system within the nucleus accumbens (NAc) in the modulation of antinociception induced by forced swim stress (FSS) remains unclear. The present study addressed the role of intra-accumbal orexin receptors in the antinociceptive responses induced by FSS during the persistent inflammatory pain model in the rat. Stereotaxic surgery was performed unilaterally on 106 adult male Wistar rats weighing 250-305 g. Different doses (1, 3, 10, and 30 nmol/ 0.5 μl DMSO) of orexin-1 receptor (OX1r) antagonist (SB334867) or OX2 receptor antagonist (TCS OX2 29) were administered into the NAc five minutes before exposure to FSS for a 6-min period. The formalin test was carried out using formalin injection (50 μl; 2.5%) into the rat's hind paw plantar surface, which induces biphasic pain-related responses. The first phase begins immediately after formalin infusion and takes 3-5 min. Subsequently, the late phase begins 15-20 min after formalin injection and takes 20-40 min. The findings demonstrated that intra-accumbal microinjection of SB334867 or TCS OX2 29 attenuated the FSS-induced antinociception in both phases of the formalin test, with the TCS OX2 29 showing higher potency. Moreover, the effect of TCS OX2 29 was more significant during the early phase of the formalin test. The results suggest that OX1 and OX2 receptors in the NAc might modulate the antinociceptive responses induced by the FSS., (Copyright © 2023. Published by Elsevier Ltd.)