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We examined 33 hypertensive (22 with comorbid type 2 diabetes mellitus (T2DM)) and 29 normotensive (8 with T2DM) middle-aged and elderly adults, comparable in age and education. Relative to normotensive participants, those with hypertension, in addition to a higher prevalence of periventricular white matter (WM) lesions, had significantly lower WM microstructural integrity of major fiber tracts as seen with MRI-based diffusion tensor imaging. Among participants with hypertension, those with co-morbid T2DM (n=22) had more widespread WM pathology than those without T2DM (n=11). Furthermore and consistent with previous research, both hypertension and T2DM were related to decreased retinal arterial diameter. Further exploratory analysis demonstrated that the observed retinal arteriolar narrowing among individual with hypertension was associated with widespread subclinical losses in WM microstructural integrity and these associations were present predominantly in the frontal lobe. We found that T2DM adds to the damaging effects of hypertension on cerebral WM, and notably these effects were independent of age and body mass index. Given that the decrease in retinal arteriolar diameter may be a biomarker for parallel pathology in cerebral arterioles, our data suggest that the frontal lobe may be particularly vulnerable to microvascular damage in the presence of hypertension and T2DM.

The aim of this audit was to quantify female representation in research on heat adaptation. Using a standardized audit tool, the PubMed database was searched for heat adaptation literature from inception to February 2023. Studies were included if they investigated heat adaptation among female and male adults (≥18–50 years) who were free from noncommunicable diseases, with heat adaptation the primary or secondary outcome of interest. The number and sex of participants, athletic caliber, menstrual status, research theme, journal impact factor, Altmetric score, Field-Weighted Citation Impact, and type of heat exposure were extracted. A total of 477 studies were identified in this audit, including 7,707 participants with ∼13% of these being female. Most studies investigated male-only cohorts (∼74%, n = 5,672 males), with ∼5% (n = 360 females) including female-only cohorts. Of the 126 studies that included females, only 10% provided some evidence of appropriate methodological control to account for ovarian hormone status, with no study meeting best-practice recommendations. Of the included female participants, 40% were able to be classified to an athletic caliber, with 67% of these being allocated to Tier 2 (i.e., trained/developmental) or below. Exercise heat acclimation was the dominant method of heat exposure (437 interventions), with 21 studies investigating sex differences in exercise heat acclimation interventions. We recommend that future research on heat adaptation in female participants use methodological approaches that consider the potential impact of sexual dimorphism on study outcomes to provide evidence-based guidelines for female athletes preparing for exercise or competition in hot conditions. [ABSTRACT FROM AUTHOR]

Abstract ConvitVax is a personalized vaccine for the treatment of breast cancer, composed of autologous tumor cells, bacillus Calmette-Guérin (BCG) and low concentrations of formalin. Previous pre-clinical studies show that this therapy induces a potent activation of the immune system and achieves an effective response against tumor cells, reducing the size of the tumor and decreasing the percentage of immunosuppressive cells. In the present study, we evaluate the toxicity of ConvitVax in healthy BALB/c mice to determine potential adverse effects related to the vaccine and each of its components. We used standard guidelines for pain, discomfort and distress recognition, continuously evaluated the site of the injection, and completed blood and urine clinical tests. Endpoint necropsy was performed, measuring the weight of organs and processing liver, kidney, thymus and lung for histological examination. Results show that the vaccine in its therapeutic dose, at 3 times its therapeutic concentration, and its individual components did not cause death or behavioral or biological changes, including any abnormalities in whole-body or organ weights, and tissue damage. These results support the safety of ConvitVax with minimal to no side-effects.

Breast cancer (BC) is the most common malignant tumor and the main cause of death in women worldwide. With increased knowledge regarding tumor escape mechanisms and advances in immunology, many new antitumor strategies such as nonspecific immunotherapies, monoclonal antibodies, anticancer vaccines, and oncolytic viruses, among others, make immunotherapy a promising approach for the treatment of BC. However, these approaches still require meticulous assessment and readjustment as resistance and modest response rates remain important barriers. In this article, we aim to summarize the most recent data available in BC immunotherapy to include the results of ongoing clinical trials and approved therapies used as monotherapies or in combination with conventional treatments. [ABSTRACT FROM AUTHOR]

Background Vascular function is compromised in Alzheimer disease (AD) years before amyloid and tau pathology are detected and a substantial body of work shows abnormal platelet activation states in patients with AD. The aim of our study was to investigate whether platelet function in middle age is independently associated with future risk of AD. Methods and Results We examined associations of baseline platelet function with incident dementia risk in the community‐based FHS (Framingham Heart Study) longitudinal cohorts. The association between platelet function and risk of dementia was evaluated using the cumulative incidence function and inverse probability weighted Cox proportional cause‐specific hazards regression models, with adjustment for demographic and clinical covariates. Platelet aggregation response was measured by light transmission aggregometry. The final study sample included 1847 FHS participants (average age, 53.0 years; 57.5% women). During follow‐up (median, 20.5 years), we observed 154 cases of incident dementia, of which 121 were AD cases. Results from weighted models indicated that platelet aggregation response to adenosine diphosphate 1.0 µmol/L was independently and positively associated with dementia risk, and it was preceded in importance only by age and hypertension. Sensitivity analyses showed associations with the same directionality for participants defined as adenosine diphosphate hyper‐responders, as well as the platelet response to 0.1 µmol/L epinephrine. Conclusions Our study shows individuals free of antiplatelet therapy with a higher platelet response are at higher risk of dementia in late life during a 20‐year follow‐up, reinforcing the role of platelet function in AD risk. This suggests that platelet phenotypes may be associated with the rate of dementia and potentially have prognostic value.

This study compared the recommended dose of sodium citrate (SC, 500 mg/kg body mass) and sodium bicarbonate (SB, 300 mg/kg body mass) for blood alkalosis (blood [HCO3−]) and gastrointestinal symptoms (GIS; number and severity). Sixteen healthy individuals ingested the supplements in a randomized, crossover design. Gelatin capsules were ingested over 15 min alongside a carbohydrate-rich meal, after which participants remained seated for forearm venous blood sample collection and completion of GIS questionnaires every 30 min for 300 min. Time-course and session value (i.e., peak and time to peak) comparisons of SC and SB supplementation were performed using linear mixed models. Peak blood [HCO3−] was similar for SC (mean 34.2, 95% confidence intervals [33.4, 35.0] mmol/L) and SB (mean 33.6, 95% confidence intervals [32.8, 34.5] mmol/L, p =.308), as was delta blood [HCO3−] (SC = 7.9 mmol/L; SB = 7.3 mmol/L, p =.478). Blood [HCO3−] was ≥6 mmol/L above baseline from 180 to 240 min postingestion for SC, significantly later than for SB (120–180 min; p <.001). GIS were mostly minor, and peaked 80–90 min postingestion for SC, and 35–50 min postingestion for SB. There were no significant differences for the number or severity of GIS reported (p >.05 for all parameters). In summary, the recommended doses of SC and SB induce similar blood alkalosis and GIS, but with a different time course. [ABSTRACT FROM AUTHOR]

Objective: Active neutrophils are important contributors to Alzheimer’s disease (AD) pathology through the formation of capillary stalls that compromise cerebral blood flow (CBF) and through aberrant neutrophil signaling that advances disease progression. The neutrophil to lymphocyte ratio (NLR) is a proxy of neutrophil-mediated inflammation, and higher NLR is found in persons diagnosed with clinical AD. The objective of this study was to investigate whether increased NLR in older adults is independently associated with the risk of subsequent dementia.Methods: We examined associations of baseline NLR with incident dementia risk in the community-based Framingham Heart Study (FHS) longitudinal cohorts. The association between NLR and risk of dementia was evaluated using the cumulative incidence function (CIF) and inverse probability-weighted Cox proportional cause-specific hazards regression models, with adjustment for age, sex, body mass index (BMI), systolic and diastolic blood pressure, diabetes, current smoking status, low-density lipoprotein (LDH), high-density lipoprotein (LDL), total cholesterol, triglycerides, and history of cardiovascular disease (CVD). Random forest survival models were used to evaluate the relative predictive value of the model covariates on dementia risk.Results: The final study sample included 1,648 participants with FHS (average age, 69 years; 56% women). During follow-up (median, 5.9 years), we observed 51 cases of incident dementia, of which 41 were AD cases. Results from weighted models suggested that the NLR was independently associated with incident dementia, and it was preceded in predictive value only by age, history of CVD, and blood pressure at baseline.Conclusion: Our study shows that individuals with higher NLR are at a greater risk of subsequent dementia during a 5.9-year follow-up period. Further evaluating the role of neutrophil-mediated inflammation in AD progression may be warranted.

This review examined the effect of acute heat mitigation strategies on physiological strain and exercise performance in females exercising in the heat. Three databases were searched for original research with an acute heat mitigation (intervention) and control strategy in active females and reporting core temperature, heart rate and/or aerobic exercise performance/capacity with ≥ 24°C wet bulb globe temperature. Hedges' g effect sizes were calculated to evaluate outcomes. Thirteen studies (n = 118) were included. Most studies that applied an acute heat mitigation strategy to females did not reduce thermal (9/10) or cardiovascular (6/6) strain or improve exercise performance/capacity (8/10). The most effective strategies for attenuating thermal strain were pre-cooling with ice-slurry (effect size = −2.2 [95% CI, −3.2, −1.1]) and ice-vests (−1.9 [−2.7, −1.1]), and pre- and per-cooling with an ice-vest (−1.8 [−2.9, −0.7]). Only pre-cooling with an ice-vest improved running performance (−1.8 [−2.9, −0.7]; ~0.43 min) whilst sodium hyperhydration improved cycling capacity at 70% V O2peak (0.8 [0.0, 1.6]; ~20.1 min). There is currently limited research on acute heat mitigation strategies in females, so the evidence for the efficacy is scarce. Some studies show beneficial effects with ice-slurry, ice-vests and sodium hyperhydration, which can guide future research to support female exercise performance in the heat. [ABSTRACT FROM AUTHOR]

Aims: To explore the relationship between nutritional intake, fermentable oligo‐, di, monosaccharides and polyols, and carbohydrate malabsorption, with gastrointestinal symptoms during a 56 km trail ultramarathon event and identify differences in nutritional intake between runners with severe and non‐severe gastrointestinal symptoms. Methods: Forty‐four ultramarathoners recorded and self‐reported dietary intake 3 days before, morning of, and during the ultramarathon with gastrointestinal symptoms obtained retrospectively and nutrient analysis via FoodWorks. Carbohydrate malabsorption was determined via breath hydrogen content pre‐ and post‐race. Spearman's rank‐order and Mann–Whitney U‐tests were used to identify relationships and differences between groups. Results: Total fermentable oligo‐, di, monosaccharides and polyols intake were not associated with gastrointestinal symptoms, but weak associations were observed for lower energy (rs = −0.302, p = 0.044) and fat intake (rs = −0.340, p = 0.024) 3 days before with upper gastrointestinal symptoms and higher caffeine intake 3 days before with overall gastrointestinal symptoms (rs = 0.314, p = 0.038). Total fermentable oligo‐, di‐, monosaccharides and polyols intake and breath hydrogen were not different between those with severe versus non‐severe symptoms (p > 0.05). Although those with severe symptoms had higher caffeine (p = 0.032), and total polyols intake (p = 0.031) 3 days before, and higher % energy from fat (p = 0.043) and sorbitol intake (p = 0.026) during the race, and slower ultramarathon finish times (p = 0.042). Conclusion: Total fermentable oligo‐, di‐, and monosaccharides intake and carbohydrate malabsorption were not associated with gastrointestinal symptoms. Additional research on the effect of fat, caffeine, and polyol intake on exercise‐associated gastrointestinal symptoms is warranted and presents new nutritional areas for consideration when planning nutritional intake for ultramarathoners. [ABSTRACT FROM AUTHOR]

Introduction The purpose of this study was to characterize using MRI the effects of a 10-week supervised exercise program on lower extremity skeletal muscle composition, nerve microarchitecture, and metabolic function in individuals with diabetic peripheral neuropathy (DPN).Research design and methods Twenty participants with DPN completed a longitudinal trial consisting of a 30-day control period, during which subjects made no change to their lifestyle, followed by a 10-week intervention program that included three supervised aerobic and resistance exercise sessions per week targeting the upper and lower extremities. The participants’ midcalves were scanned with multinuclear MRI two times prior to intervention (baseline1 and baseline2) and once following intervention to measure relaxation times (T1, T1ρ, and T2), phosphocreatine recovery, fat fraction, and diffusion parameters.Results There were no changes between baseline1 and baseline2 MRI metrics (p>0.2). Significant changes (p0.3) and tibial nerve fractional anisotropy (p>0.6) and apparent diffusion coefficient (p>0.4).Conclusions The 10-week supervised exercise intervention program successfully reduced adiposity and altered resting tissue properties in the lower leg in DPN. Gastrocnemius mitochondrial oxidative capacity and tibial nerve microarchitecture changes were not observed, either due to lack of response to therapy or to lack of measurement sensitivity.

Buffering agents have not been comprehensively profiled in terms of their capacity to influence water retention prior to exercise. The purpose of this investigation was to profile the fluid retention characteristics of sodium bicarbonate (BIC) and sodium citrate (CIT) to determine the efficacy of these buffering mediums as hyperhydrating agents. Nineteen volunteers (13 males and six females; age = 28.3 ± 4.9 years) completed three trials (randomized and cross-over design). For each trial, a baseline measurement of body mass, capillary blood, and urine was collected prior to ingestion of their respective condition (control condition [CON] = 25 ml/kg artificially sweetened water; BIC condition = CON + 7.5 g/L of sodium in the form of BIC; CIT condition = CON + 7.5 g/L of sodium in the form of CIT). The fluid loads were consumed in four equal aliquots (0, 20, 40 and 60 min; fluid intake was 1.972 ± 361 ml [CON]; 1.977 ± 360 ml [BIC]; 1.953 ± 352 ml [CIT]). Samples were recorded at 20 (body mass and urine) and 60 min (blood) intervals for 180 min. Blood buffering capacity (HCO3−) was elevated (p <.001) in both BIC (32.1 ± 2.2 mmol/L) and CIT (28.9 ± 3.8 mmol/L) at 180 min compared with CON (25.1 ± 1.8 mmol/L). Plasma volume expansion was greater (p <.001) in both BIC (8.1 ± 1.3%) and CIT (5.9 ± 1.8%) compared with CON (−1.1 ± 1.4%); whereas, total urine production was lower in BIC and CIT at 180 min (BIC vs. CON, mean difference of 370 ± 85 ml; p <.001; CIT vs. CON, mean difference of 239 ± 102 ml; p =.05). There were no increases observed in body mass (p =.9). Under resting conditions, these data suggest BIC and CIT induce a greater plasma hypervolemic response as compared with water alone. [ABSTRACT FROM AUTHOR]

Abstract Aims/hypothesis Midlife obesity is a risk factor for dementia. We investigated the impact of obesity on brain structure, metabolism, and cerebrospinal fluid (CSF) core Alzheimer's disease (AD) biomarkers in healthy elderly. Methods We selected controls from ADNI2 with CSF AD biomarkers and/or fluorodeoxyglucose positron emission tomography (FDG‐PET) and 3T‐MRI. We measured cortical thickness, FDG uptake, and CSF amyloid beta (Aβ)1‐42, p‐tau, and t‐tau levels. We performed regression analyses between these biomarkers and body mass index (BMI). Results We included 201 individuals (mean age 73.5 years, mean BMI 27.4 kg/m2). Higher BMI was related to less cortical thickness and higher metabolism in brain areas typically not involved in AD (family‐wise error [FWE]

Aim: This systematic literature review with meta‐analysis aimed to determine the effect of omega‐3 long chain polyunsaturated fatty acids on prostaglandin levels and pain severity in women with dysmenorrhoea and identify adverse side effects. Methods: A literature search was conducted in Embase, Scopus, Web of Science, MEDLINE complete, CINAHL and AMED databases (PROSPERO CRD42022340371). Included studies provided omega‐3 long chain polyunsaturated fatty acids compared to a control in women with dysmenorrhoea and reported pain and/or prostaglandin levels. A random effects meta‐analysis with Cohen's d effect size (95% confidence interval) was performed in SPPS for studies that reported pain outcomes. Study quality was assessed using the Academy of Nutrition and Dietetics Quality Criteria Checklist. Results: Twelve studies (n = 881 dysmenorrhoeal women) of predominantly neutral quality (83%) were included that provided daily supplementation of 300–1800 mg omega‐3 long chain polyunsaturated fatty acids over 2 or 3 months. Meta‐analysis (n = 8 studies) showed a large effect of omega‐3 long chain polyunsaturated fatty acids (d = −1.020, 95% confidence interval −1.53 to −0.51) at reducing dysmenorrhoea pain. No studies measured prostaglandin levels, 86% of studies measuring analgesic use showed a reduction with omega‐3 long chain polyunsaturated fatty acids and few studies reported mild adverse side effects in individual participants. Conclusions: Findings suggest that daily supplementation of 300–1800 mg omega‐3 long chain polyunsaturated fatty acids over 2–3 months are generally well tolerated and reduces pain and analgesic use in women with dysmenorrhoea. However, the neutral quality of research is limited by methodological issues and the mechanism of action remains to be determined. [ABSTRACT FROM AUTHOR]

Copyright of Gaceta Médica de Caracas is the property of Academia Nacional de Medicina and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Several mycobacterial antigens, identified by monoclonal antibodies and patient sera, have been found to be homologous to stress or heat-shock proteins (hsp) defined in Escherichia coli and yeast. A major antigen recognized by most Mycobacterium leprae-reactive human T cell lines and cell wall-reactive T cell clones is a 10-kD protein that has now been cloned and sequenced. The predicted amino acid sequence of this protein is 44% homologous to the hsp 10 (GroES) of E. coli. The purified native and recombinant 10-kD protein was found to be a stronger stimulator of peripheral blood T cell proliferation than other native and recombinant M. leprae proteins tested. The degree of reactivity paralleled the response to intact M. leprae throughout the spectrum of leprosy. Limiting-dilution analysis of peripheral blood lymphocytes from a patient contact and a tuberculoid patient indicated that approximately one third of M. leprae-reactive T cell precursors responded to the 10-kD antigen. T cell lines derived from lepromin skin tests were strongly responsive to the 10-kD protein. T cell clones reactive to both the purified native and recombinant 10-kD antigens recognized M. leprae-specific epitopes as well as epitopes crossreactive with the cognate antigen of M. tuberculosis. Further, the purified hsp 10 elicited strong delayed-type hypersensitivity reactions in guinea pigs sensitized to M. leprae. The strong T cell responses against the M. leprae 10-kD protein suggest a role for this heat-shock cognate protein in the protective/resistant responses to infection.

Much of the effort to understand the brain substrate of theory of mind and empathy has involved the study of individuals with deficits in that domain, such as those on the autism spectrum. Studying individuals with presumed superior abilities in picking up social signals may yield important additional information. We predicted that psychic readers may have superior abilities and tested this by contrasting a group of 22 professional psychic readers with matched controls on a measure of theory of mind (''Reading the Mind in the Eyes'' test) and a multidimensional measure of empathy [Interpersonal Reactivity Index (IRI)]. Although psychic readers were not superior in reading the language of the eyes, they were shown to have more cognitive empathy, as measured with the ''Fantasy'' subscale of the IRI. We discuss the merits of research involving ''experts'' in social cognition and propose other possible groups of ''master mindreaders.''

Copyright of Gaceta Médica de Caracas is the property of Academia Nacional de Medicina and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Leprosy is a slowly evolving disease that occurs mainly in adults. In this study, the Mamaría Village, state of Portuguesa was selected because it had one of the highest prevalence rates (13.25%) of leprosy cases in 1997. Between 1998-2004, 20.2% of the 89 cases registered in this village were less than 15 years old and 61.8% were males. Pau-cibacillary (PB) lesions were the predominant clinical forms identified, although also multibacillary (MB) forms were found. Additionally, 76% of the patients were bacteriologically negative. At the time of diagnosis, 75% of the patients presented with grade 0 disabilities, 23% with grade 1 and 2% with grade 2. Serum samples were collected from 18 PB and 15 MB patients, in addition to 14 family contacts, at the beginning and end of treatment. All the groups were re-evaluated during a three-year period (2008-2011). The proteins used for evaluation were ML0405, ML2331 and LID-1. These mycobacterial proteins were highly specific for Mycobacterium leprae and the IgG responses decreased in both MB and PB patients during multidrug treatment. Our results suggest that these antigens could be used as markers for successful treatment of non-reactional lepromatous patients.

William K Wedin,1 Lizmer Diaz-Gimenez,1 Antonio J Convit1,21Department of Psychiatry, NYU School of Medicine, New York, NY, USA; 2Nathan Kline Institute, Orangeburg, NY, USAObjective: The aim of this study was to describe the minimum number of anthropometric measures that will optimally predict insulin resistance (IR) and to characterize the utility of these measures among obese and nonobese adolescents.Research design and methods: Six anthropometric measures (selected from three categories: central adiposity, weight, and body composition) were measured from 1298 adolescents attending two New York City public high schools. Body composition was determined by bioelectric impedance analysis (BIA). The homeostatic model assessment of IR (HOMA-IR), based on fasting glucose and insulin concentrations, was used to estimate IR. Stepwise linear regression analyses were performed to predict HOMA-IR based on the six selected measures, while controlling for age.Results: The stepwise regression retained both waist circumference (WC) and percentage of body fat (BF%). Notably, BMI was not retained. WC was a stronger predictor of HOMA-IR than BMI was. A regression model using solely WC performed best among the obese II group, while a model using solely BF% performed best among the lean group. Receiver operator characteristic curves showed the WC and BF% model to be more sensitive in detecting IR than BMI, but with less specificity.Conclusion: WC combined with BF% was the best predictor of HOMA-IR. This finding can be attributed partly to the ability of BF% to model HOMA-IR among leaner participants and to the ability of WC to model HOMA-IR among participants who are more obese. BMI was comparatively weak in predicting IR, suggesting that assessments that are more comprehensive and include body composition analysis could increase detection of IR during adolescence, especially among those who are lean, yet insulin-resistant.Keywords: BMI, bioelectrical impedance analysis, waist circumference, HOMA, insulin resistance, type 2 diabetes