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Limb, sex, but not acute dietary capsaicin, modulate the near-infrared spectroscopy-vascular occlusion test estimate of muscle metabolism.
Greaves, LM, Zaleski, KS, Matias, AA, Gyampo, AO, Giuriato, G, Lynch, M, Lora, B, Tomasi, T, Basso, E, Finegan, E, et al
Physiological reports. 2024;(6):e15988
Abstract
The downward slope during the near-infrared spectroscopy (NIRS)-vascular occlusion test (NIRS-VOT) is purported as a simplified estimate of metabolism. Whether or not the NIRS-VOT exhibits sex- or limb-specificity or may be acutely altered remains to be elucidated. Thus, we investigated if there is limb- or sex specificity in tissue desaturation rates (DeO2) during a NIRS-VOT, and if acute dietary capsaicin may alter this estimate of muscle metabolism. Young healthy men (n = 25, 21 ± 4 years) and women (n = 20, 20 ± 1 years) ingested either placebo or capsaicin, in a counterbalanced, single-blind, crossover design after which a simplified NIRS-VOT was conducted to determine the DeO2 (%/s), as an estimate of oxidative muscle metabolism, in both the forearm (flexors) and thigh (vastus lateralis). There was a significant limb effect with the quadriceps having a greater DeO2 than the forearm (-2.31 ± 1.34 vs. -1.78 ± 1.22%/s, p = 0.007, ηp 2 = 0.19). There was a significant effect of sex on DeO2 (p = 0.005, ηp 2 = 0.203) with men exhibiting a lesser DeO2 than women (-1.73 ± 1.03 vs. -2.36 ± 1.32%/s, respectively). This manifested in significant interactions of limb*capsaicin (p = 0.001, ηp 2 = 0.26) as well as limb*capsaicin*sex on DeO2 (p = 0.013, ηp 2 = 0.16) being observed. Capsaicin does not clearly alter O2-dependent muscle metabolism, but there was apparent limb and sex specificity, interacting with capsaicin in this NIRS-derived assessment.
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High dose cholecalciferol supplementation causing morning blood pressure reduction in patients with type 1 diabetes mellitus and cardiovascular autonomic neuropathy.
Felício, J, Moraes, L, Lemos, G, Souza, Í, Vieira, G, Silva, L, Queiroz, N, Souza, AC, Melo, F, Neto, JFA, et al
Scientific reports. 2024;(1):6374
Abstract
We evaluated the association of cardiovascular autonomic neuropathy (CAN), blood pressure (BP) and Vitamin D (VD) levels before and after high-dose cholecalciferol supplementation (4000/10,000) UI/day) for 12 weeks in patients (N = 67) with type 1 diabetes mellitus (T1DM). Based on this prospective controlled pilot study, patients were divided into group 1 (N = 23 with CAN) and group 2 (N = 44 without CAN). At baseline, group 1 had higher systolic BP (SBP) during sleep (115 ± 14 vs. 107 ± 12 mmHg, p = 0.04) and lower nocturnal dipping (3 ± 5 vs. 8 ± 6%, p = 0.009). Among those with loss of nocturnal dipping, 45.4% (20/44) had CAN, while in normal nocturnal dipping group it occurred only in 13% (3/23) (p = 0.007). Non-dipper group had worse CAN parameters when compared to dipper group [Very low frequency (VLF) (2.5 ± 0.5vs.2.8 ± 0.4 s, p = 0.01), total power (TP) (2.9 ± 0.6 vs. 3.3 ± 0.4 s, p = 0.01), Valsalva coefficient (1.5 ± 0.4 vs. 1.8 ± 0.6, p = 0.06)]. After VD, only group 1 improved CAN parameters [TP (2.5 ± 0.4 vs. 2.8 ± 0.6, p = 0.01) and VLF (2.2 ± 0.4 vs. 2.4 ± 0.5, p = 0.03). Group 1 presented a reduction in morning SBP (120 ± 20 vs. 114 ± 17 mmHg, p = 0.038) and in morning SBP surge (13 ± 13 vs. 5 ± 14, p = 0.04). High-dose VD was associated with improved CAN parameters and reduced awake SBP and morning SBP surge. These findings suggest that VD may benefit patients with cardiovascular autonomic neuropathy. ISRCTN32601947, registration date: 31/07/2017.
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Sweat induction using Pilocarpine microneedle patches for sweat testing in healthy adults.
Chen, JY, Li, S, Silva, GL, Chandler, JD, Prausnitz, MR, Guglani, L
Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 2024;(1):112-119
Abstract
BACKGROUND The sweat test using pilocarpine iontophoresis remains the gold standard for diagnosing cystic fibrosis, but access and reliability are limited by specialized equipment and insufficient sweat volume collected from infants and young children. These shortcomings lead to delayed diagnosis, limited point-of-care applications, and inadequate monitoring capabilities. METHODS We created a skin patch with dissolvable microneedles (MNs) containing pilocarpine that eliminates the equipment and complexity of iontophoresis. Upon pressing the patch to skin, the MNs dissolve in skin to release pilocarpine for sweat induction. We conducted a non-randomized pilot trial among healthy adults (clinicaltrials.gov, NCT04732195) with pilocarpine and placebo MN patches on one forearm and iontophoresis on the other forearm, followed by sweat collection using Macroduct collectors. Sweat output and sweat chloride concentration were measured. Subjects were monitored for discomfort and skin erythema. RESULTS Fifty paired sweat tests were conducted in 16 male and 34 female healthy adults. MN patches delivered similar amounts of pilocarpine into skin (1.1 ± 0.4 mg) and induced equivalent sweat output (41.2 ± 25.0 mg) compared to iontophoresis (1.2 ± 0.7 mg and 43.8 ± 32.3 mg respectively). Subjects tolerated the procedure well, with little or no pain, and only mild transient erythema. Sweat chloride concentration measurements in sweat induced by MN patches (31.2 ± 13.4 mmol/L) were higher compared to iontophoresis (24.0 ± 13.2 mmol/L). Possible physiological, methodological, and artifactual causes of this difference are discussed. CONCLUSIONS Pilocarpine MN patches present a promising alternative to iontophoresis to enable increased access to sweat testing for in-clinic and point-of-care applications.
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Development and effectiveness of a mobile-based autonomy support program for the prevention of metabolic syndrome in middle-aged women.
Seo, M, Jun, EY, Oh, H
Frontiers in public health. 2024;:1334988
Abstract
OBJECTIVE Utilizing self-directed strategies for maintaining and managing healthy lifestyle habits is efficient, and it is essential to consider individual motivation, as it is a factor that directly influences the adoption and maintenance of healthy behaviors. The study aimed to assess the effects of a mobile-based autonomy support program on basic psychological needs, autonomous motivation, health behavior, and metabolic syndrome indicators in middle-aged women. METHODS This study was a non-randomized controlled trial with a pre-test and post-test design, focused on validating a mobile-based autonomy-supportive program to prevent metabolic syndrome in middle-aged women. The experimental group participated in a 12-week mobile-based autonomy support program, which included components such as education, physical activity guidance, dietary management, and real-time data monitoring. In contrast, the control group was provided with comparable educational resources. Assessments of basic psychological needs, autonomous motivation, health behavior, and metabolic syndrome indicators were conducted at baseline and again at the 12-week mark. RESULTS After a 12-week period, the experimental group demonstrated significant enhancements in autonomy (p = 0.004) and competence (p < 0.001), two key dimensions of basic psychological needs. Autonomous motivation (p < 0.001) and health behavior scores (p < 0.001) were also significantly higher in the experimental group, while waist circumference (p = 0.048) and systolic blood pressure (p = 0.011) were significantly reduced. Other variables such as relatedness, high-density cholesterol, fasting blood sugar, diastolic blood pressure, and neutral fat scores were also improved in the experimental group, but these changes were not statistically significant. CONCLUSION The autonomy support program offers a cost-effective and community-accessible health care strategy for middle-aged women and may be integrated into various nursing practices.
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Microbial-derived imidazole propionate links the heart failure-associated microbiome alterations to disease severity.
Raju, SC, Molinaro, A, Awoyemi, A, Jørgensen, SF, Braadland, PR, Nendl, A, Seljeflot, I, Ueland, PM, McCann, A, Aukrust, P, et al
Genome medicine. 2024;(1):27
Abstract
BACKGROUND Interactions between the gut microbiota, diet, and host metabolism contribute to the development of cardiovascular disease, but a firm link between disease-specific gut microbiota alterations and circulating metabolites is lacking. METHODS We performed shot-gun sequencing on 235 samples from 166 HF patients and 69 healthy control samples. Separate plasma samples from healthy controls (n = 53) were used for the comparison of imidazole propionate (ImP) levels. Taxonomy and functional pathways for shotgun sequencing data was assigned using MetaPhlAn3 and HUMAnN3 pipelines. RESULTS Here, we show that heart failure (HF) is associated with a specific compositional and functional shift of the gut microbiota that is linked to circulating levels of the microbial histidine-derived metabolite ImP. Circulating ImP levels are elevated in chronic HF patients compared to controls and associated with HF-related gut microbiota alterations. Contrary to the microbiota composition, ImP levels provide insight into etiology and severity of HF and also associate with markers of intestinal permeability and systemic inflammation. CONCLUSIONS Our findings establish a connection between changes in the gut microbiota, the presence, etiology, and severity of HF, and the gut-microbially produced metabolite ImP. While ImP appears promising as a circulating biomarker reflecting gut dysbiosis related to HF, further studies are essential to demonstrate its causal or contributing role in HF pathogenesis. TRIAL REGISTRATION NCT02637167, registered December 22, 2015.
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Gut microbiome and serum amino acid metabolome alterations in autism spectrum disorder.
Chang, X, Zhang, Y, Chen, X, Li, S, Mei, H, Xiao, H, Ma, X, Liu, Z, Li, R
Scientific reports. 2024;(1):4037
Abstract
Gut microbiota and their metabolic products might play important roles in regulating the pathogenesis of autism spectrum disorder (ASD). The purpose of this study was to characterize gut microbiota and serum amino acid metabolome profiles in children with ASD. A non-randomized controlled study was carried out to analyze the alterations in the intestinal microbiota and their metabolites in patients with ASD (n = 30) compared with neurotypical controls (NC) (n = 30) by metagenomic sequencing to define the gut microbiota community and liquid chromatography/mass spectrometry (LC/MS) analysis to characterize the metabolite profiles. Compared with children in the NC group, those in the ASD group showed lower richness, higher evenness, and an altered microbial community structure. At the class level, Deinococci and Holophagae were significantly lower in children with ASD compared with TD. At the phylum level, Deinococcus-Thermus was significantly lower in children with ASD compared with TD. In addition, the functional properties (such as galactose metabolism) displayed significant differences between the ASD and NC groups. Five dominant altered species were identified and analyzed (LDA score > 2.0, P < 0.05), including Subdoligranulum, Faecalibacterium_praushitzii, Faecalibacterium, Veillonellaceae, and Rumminococcaceae. The peptides/nickel transport system was the main metabolic pathway involved in the differential species in the ASD group. Decreased ornithine levels and elevated valine levels may increase the risk of ASD through a metabolic pathway known as the nickel transport system. The microbial metabolism in diverse environments was negatively correlated with phascolarctobacterium succinatutens. Our study provides novel insights into compositional and functional alterations in the gut microbiome and metabolite profiles in ASD and the underlying mechanisms between metabolite and ASD.
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Neurostimulation for Advanced Parkinson Disease and Quality of Life at 5 Years: A Nonrandomized Controlled Trial.
Jost, ST, Aloui, S, Evans, J, Ashkan, K, Sauerbier, A, Rizos, A, Petry-Schmelzer, JN, Gronostay, A, Fink, GR, Visser-Vandewalle, V, et al
JAMA network open. 2024;(1):e2352177
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Abstract
IMPORTANCE Deep brain stimulation of the subthalamic nucleus (STN-DBS) improves quality of life (QOL) in patients with advanced Parkinson disease (PD). However, controlled studies with more than 3 years of follow-up are lacking. OBJECTIVE To investigate the long-term effects of STN-DBS on QOL compared with standard-of-care medication (MED). DESIGN, SETTING, AND PARTICIPANTS In this prospective, observational, quasi-experimental, longitudinal nonrandomized controlled trial, 183 patients were screened for eligibility and 167 were enrolled from March 1, 2011, to May 31, 2017, at 3 European university centers. Propensity score matching for demographic and clinical characteristics was applied to 108 patients with PD (62 in the STN-DBS group and 46 in the MED group), resulting in a well-balanced, matched subcohort of 25 patients per group. Data analysis was performed from September 2022 to January 2023. EXPOSURE Treatment for PD of STN-DBS or MED. MAIN OUTCOMES AND MEASURES Assessments included Parkinson's Disease Questionnaire 8 (PDQ-8), Unified PD Rating Scale-motor examination, Scales for Outcomes in PD-activities of daily living (ADL) and motor complications, and levodopa-equivalent daily dose. Within-group longitudinal outcome changes, between-group differences, and correlations of change scores were analyzed. RESULTS The study population in the analysis included 108 patients (mean [SD] age, 63.7 [8.3] years; 66 [61.1%] male). At 5-year follow-up, PDQ-8 and ADL worsened only in the MED group (PDQ-8 change, -10.9; 95% CI, -19.0 to -2.7; P = .01; ADL change: -2.0; 95% CI, -3.1 to -0.8; P = .002), whereas both outcomes remained stable in the STN-DBS group (PDQ-8 change, -4.3; 95% CI, -13.2 to 4.7; P = .34; ADL change, -0.8; 95% CI, -2.5 to 1.0; P = .38). Changes in PDQ-8 and ADL correlated moderately (rs = .40, P = .008). Furthermore, STN-DBS outcomes were favorable for motor complications (median difference in change scores between STN-DBS and MED, -2.0; 95% CI, -4.0 to -1.0; P = .003), mobility (-1.0; 95% CI, -2.0 to 0; P = .03), and levodopa-equivalent daily dose reduction (-821.4; 95% CI, -1111.9 to -530.8; P < .001). CONCLUSIONS AND RELEVANCE This study provides evidence of differences in QOL outcomes at 5-year follow-up between STN-DBS (stable) and MED (worsened), mainly driven by the favorable effect of STN-DBS on mobility (class IIb evidence). The association between changes in QOL and ADL, but not motor impairment or complications, highlights the relative importance of ADL outcomes for long-term DBS assessments. TRIAL REGISTRATION German ClinicalTrials Registry: DRKS00006735.
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Prior acute exercise restores postprandial fat oxidation in active cannabis users.
Schubert, MM, Terauds, S, Plant, M, Handler, G, Atkins, C, Mendez, C
Physiological reports. 2024;(5):e15968
Abstract
Data suggest cannabis users have similar or lower levels of blood lipids compared to nonusers. However, the extent to which cannabis users experience postprandial lipemia is not known. Eleven cannabis users and 11 nonusers completed either rest or 1 h of exercise at their ventilatory threshold the evening before a meal tolerance test (MTT). Substrate oxidation, blood pressure, and capillary blood were obtained before and every 30-60 min post-meal for 3 h. Linear mixed models were utilized to examine differences in variables between groups, conditions, across time, and their interactions. Exercise led to increased fat oxidation post-MTT (p < 0.05), with cannabis users exhibiting higher AUC compared to the control trial (p < 0.05). Exercise also caused significantly lower levels of triglycerides (p < 0.05). Metabolic flexibility was improved in cannabis users in the exercise trial only (p < 0.05). No effect of group, trial, or interactions were detected for other variables of interest (all p > 0.05). This study indicated that prior exercise improves lipid metabolism in cannabis users and nonusers after a high-fat meal test. Cannabis users appear sensitive to the effects of exercise. Future studies should incorporate additional meals and variables related to cardiovascular health and metabolism.
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Effectiveness of locally produced ready-to-use supplementary foods on the prevention of stunting in children aged 6-23 months: a community-based trial from Pakistan.
Fazid, S, Haq, ZU, Gillani, BH, Khan, AJ, Khan, MN, Khan, A, Garzon, C, Habib, I, Tanimoune, M, Ihtesham, Y, et al
The British journal of nutrition. 2024;(7):1189-1195
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Abstract
Undernutrition is a major public health problem in developing countries. Around 40·2 % of children are stunted in Pakistan. This longitudinal study aimed to assess the effectiveness of locally produced ready-to-use supplementary foods in the prevention of stunting by detecting change in of children in intervention v. control arm against the 2006 WHO growth reference. A community-based non-randomised cluster-controlled trial was conducted from January 2018 to December 2020 in the district of Kurram, Khyber Pakhtunkhwa, Pakistan. A total of 80 clusters (each cluster comprising ≈ 250-300 households) were defined in the catchment population of twelve health facilities. Children aged 6-18 months were recruited n 1680. The intervention included a daily ration of 50 g - locally produced ready-to-use-supplementary food (Wawa-Mum). The main outcome of this study was a change in length for age z-score (LAZ) v. WHO growth standards. Comparison between the interventions was by t test and ANOVA. Cox proportional hazard models were used to assess the association between stunting occurrence and the utilisation of locally produced supplement. Out of the total 1680, fifty-one out of the total 1680, 51·1 out of the total 1680 and 51·1 % (n 859) were male. Mean age 13·9 months (sd + 859) were male. Mean age 13·9 months (sd + -4·4). At baseline, 36·9 % (n 618) were stunted. In the intervention group, mean LAZ score significantly increased from -1·13(2·2 sd) at baseline to -0·93(1·8 sd) at 6-month follow-up (P value 0·01) compared with the control group. The incidence rate of stunting in the intervention arm was 1·3 v. 3·4 per person year in the control arm. The control group had a significantly increased likelihood of stunting (Hazard Ratio (HR) 1·7, 95 % CI 1·46, 2·05, P value < 0·001) v. the intervention group. Locally produced ready-to-use supplementary food is an effective intervention for reducing stunting in children below 2 years of age. This can be provided as part of a malnutrition prevention package to overcome the alarming rates of stunting in Pakistan.
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Prediction of Cerebral Palsy or Death among Preterm Infants Who Survive the Neonatal Period.
Peaceman, AM, Mele, L, Rouse, DJ, Leveno, KJ, Mercer, BM, Varner, MW, Reddy, UM, Wapner, RJ, Sorokin, Y, Thorp, JM, et al
American journal of perinatology. 2024;(6):783-789
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OBJECTIVE To assess whether neonatal morbidities evident by the time of hospital discharge are associated with subsequent cerebral palsy (CP) or death. STUDY DESIGN This is a secondary analysis of data from a multicenter placebo-controlled trial of magnesium sulfate for the prevention of CP. The association between prespecified intermediate neonatal outcomes (n = 11) and demographic and clinical factors (n = 10) evident by the time of discharge among surviving infants (n = 1889) and the primary outcome of death or moderate/severe CP at age 2 (n = 73) was estimated, and a prediction model was created. RESULTS Gestational age in weeks at delivery (odds ratio [OR]: 0.74, 95% confidence interval [CI]: 0.67-0.83), grade III or IV intraventricular hemorrhage (IVH) (OR: 5.3, CI: 2.1-13.1), periventricular leukomalacia (PVL) (OR: 46.4, CI: 20.6-104.6), and male gender (OR: 2.5, CI: 1.4-4.5) were associated with death or moderate/severe CP by age 2. Outcomes not significantly associated with the primary outcome included respiratory distress syndrome, bronchopulmonary dysplasia, seizure, necrotizing enterocolitis, neonatal hypotension, 5-minute Apgar score, sepsis, and retinopathy of prematurity. Using all patients, the receiver operating characteristic curve for the final prediction model had an area under the curve of 0.84 (CI: 0.78-0.89). Using these data, the risk of death or developing CP by age 2 can be calculated for individual surviving infants. CONCLUSION IVH and PVL were the only neonatal complications evident at discharge that contributed to an individual infant's risk of the long-term outcomes of death or CP by age 2. A model that includes these morbidities, gestational age at delivery, and gender is predictive of subsequent neurologic sequelae. KEY POINTS · Factors known at hospital discharge are identified which are independently associated with death or CP by age 2.. · A model was created and validated using these findings to counsel parents.. · The risk of death or CP can be calculated at the time of hospital discharge..