Anal Cancers in Previously Screened Versus Unscreened Patients: Tumor Stage and Treatment Outcomes.

BACKGROUND: Targeted screening programs for patients at high risk for anal squamous-cell carcinoma have been proposed; however, the evidence in support of screening remains unclear. OBJECTIVE: This study aimed to determine whether screening high-risk patients (predominantly those living with HIV) detected squamous-cell carcinoma at an earlier stage compared to the routine practice of not screening. DESIGN: This is a cohort study. SETTINGS: This study was conducted at a quaternary care center in Canada. PATIENTS: Included patients were at least 18 years old with a pathologic diagnosis of invasive anal squamous-cell carcinoma between 2002 and 2022. INTERVENTIONS: Patients diagnosed through a high-risk screening program were compared to those who did not undergo screening. MAIN OUTCOME MEASURES: The primary outcome was clinical stage at presentation, categorized as T1N0M0 vs other. Secondary outcomes included treatments received, treatment failure, and overall survival. RESULTS: A total of 612 patients with anal squamous-cell carcinoma were included, with 26 of those patients diagnosed through a screening program. Patients with screen-detected cancers had greater odds of presenting with T1N0M0 tumors compared to unscreened patients (18 [69.2%] vs 84 [14.3%]; adjusted OR 9.95; 95% CI, 3.95-25.08). A propensity score-matched sensitivity analysis found similar results (OR 11.13; 95% CI, 4.67-26.52). Screened patients had greater odds of treatment with wide local excision alone, as opposed to any combination of chemotherapy, radiation therapy, and surgery (3 [12.5%] vs 18 [3.2%]; OR 4.38; 95% CI, 1.20-16.04). There were no statistically significant differences in treatment failure or overall survival between groups. LIMITATIONS: The small number of screened patients limits the power of the analysis. CONCLUSIONS: Screening for anal squamous-cell carcinoma among high-risk populations detects cancers at an earlier stage. Patients with screen-detected cancers also had a greater likelihood of being candidates for wide local excision alone, which may have spared them the morbidity associated with chemoradiotherapy or abdominoperineal resection. See Video Abstract. CNCERES DE ANO EN PACIENTES PREVIAMENTE DETECTADOS POR CRIBADO VERSUS NO DETECTADOS ESTADIO DEL TUMOR Y RESULTADOS DEL TRATAMIENTO: ANTECEDENTES:Se han propuesto programas de cribado dirigidos a pacientes con alto riesgo de carcinoma anal de células escamosas; sin embargo, la evidencia a favor de la detección sigue sin estar clara.OBJETIVO:Este estudio tuvo como objetivo determinar si el cribado de pacientes de alto riesgo (predominantemente aquellos que viven con el VIH) detectó el carcinoma de células escamosas en una etapa más temprana en comparación con la práctica habitual de no cribado.DISEÑO:Este es un estudio de cohortes.CONFIGURACIÓN:Este estudio se realizó en un centro de atención cuaternaria en Canadá.PACIENTES:Los pacientes incluidos tenían al menos 18 años con un diagnóstico patológico de carcinoma de células escamosas anal invasivo entre 2002 y 2022.INTERVENCIONES:Los pacientes diagnosticados mediante un programa de cribado de alto riesgo se compararon con aquellos que no se sometieron a cribado.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue el estadio clínico en la presentación, categorizado como T1N0M0 versus otro. Los resultados secundarios incluyeron los tratamientos recibidos, el fracaso del tratamiento y la supervivencia general.RESULTADOS:Se incluyeron un total de 612 pacientes con carcinoma anal de células escamosas, con 26 de esos pacientes diagnosticados a través de un programa de cribado. Los pacientes con cánceres detectados mediante cribado tenían mayores probabilidades de presentar tumores T1N0M0 en comparación con los pacientes no cribados (18 [69.2%] frente a 84 [14.3%]; razón de probabilidad ajustada 9.95; intervalo de confianza del 95 % 3.95 -25.08). Un análisis de sensibilidad emparejado por puntaje de propensión encontró resultados similares (odds ratio 11.13; intervalo de confianza del 95% 4.67 -26.52; p < 0.001). Los pacientes examinados tenían mayores probabilidades de recibir tratamiento con escisión local amplia sola, en comparación con cualquier combinación de quimioterapia, radiación y cirugía (3 [12.5%] frente a 18 [3.2%]; razón de probabilidad 4.38; intervalo de confianza del 95 % 1.20 -16.04). No hubo diferencias estadísticamente significativas en el fracaso del tratamiento o la supervivencia global entre los grupos.LIMITACIONES:El pequeño número de pacientes evaluados limita el poder del análisis.CONCLUSIONES:La detección del carcinoma anal de células escamosas entre las poblaciones de alto riesgo detecta los cánceres en una etapa más temprana. Los pacientes con cánceres detectados mediante cribado también tenían una mayor probabilidad de ser candidatos para una escisión local amplia sola, lo que puede haberles evitado la morbilidad asociada con la quimiorradioterapia o la resección abdominoperineal. (Traducción --Dr. Aurian Garcia Gonzalez ).

Low-Level Anorectal HIV Shedding despite Effective Antiretroviral Therapy Is Not Driven by Mucosal Inflammation.

Although antiretroviral treatment (ART) suppresses HIV RNA in blood and prevents transmission, low-level anorectal HIV RNA shedding persists in some ART-treated men who have sex with men. We collected anorectal biopsies and swabs from 55 men who have sex with men on effective ART, hypothesizing that anorectal shedding would be linked to microbiota-driven mucosal T cell activation. Lymphocytes were assessed by flow cytometry, soluble immune factors by multiplex immunoassay, neutrophils and epithelial integrity by immunofluorescence microscopy, and the anorectal microbiome by quantitative PCR and 16S rRNA gene sequencing. Unexpectedly, we found no evidence that anorectal HIV shedding was associated with the parameters of mucosal inflammation, including T cell activation, inflammatory cytokines, the density of neutrophils, or epithelial integrity. Moreover, the anorectal bacterial load was actually lower in the shedding group, with no major differences in bacterial composition. Instead, the strongest mucosal immune correlates of HIV shedding were an increase in central memory cell frequency and Ki67 expression as well as higher concentrations of the cytokine IL-7 in anorectal secretions. Anorectal HIV RNA shedding during effective ART was not driven by local inflammation; the associations seen with local homeostatic T cell proliferation will require further confirmation.

Low Energy Availability and Increased Risk of Relative Energy Deficiency in Sport (RED-S) During a 3767-km Thru-Hike on the Pacific Crest Trail: A Case Study.

Long-distance "thru-hiking" has extraordinary physical demands and has become increasingly popular. This report describes a man (55 y) who thru-hiked the Pacific Crest Trail in 2021 and was at risk of developing the relative energy deficiency in sport (RED-S) syndrome. Hiking distance was 3767 km over 128 d. Eighty-eight days (69%) were full days of hiking, covering 38±8 km/d (mean±SD) in 7.9±1.6 h/d. Exercise energy expenditure above rest (heart rate vs indirect calorimetry regression method) was 2834±1518 kcal/d, total energy expenditure was 5702±1323 kcal/d, and energy intake was 4141 kcal/d. Body mass decreased by 9%, and fat mass (dual-energy X-ray absorptiometry) decreased by 46%. Energy availability (energy intake minus exercise energy expenditure) was 19.3 kcal/d/kg fat-free mass, indicating low energy availability (defined as <30 kcal/d/kg). Dual-energy X-ray absorptiometry-measured spine bone mineral density (BMD) decreased by 8.6%, with little to no decrease in total hip (-1.0%) and femoral neck (-1.5%) BMD. Total cholesterol, low-density lipoprotein cholesterol, and triglycerides increased by 24, 39, and 57%, respectively. Within 8 mo after the hike, BMD and serum lipids nearly or fully returned to baseline. No changes in high-density lipoprotein cholesterol, glycemia, or blood pressure were observed. According to guidelines, these observations are consistent with a moderate risk of RED-S, and a medical evaluation and treatment plan are advisable in order to avoid clinical manifestations (eg, stress fractures, anemia, psychological disturbances). To minimize RED-S risk, it may be prudent for thru-hikers to optimize energy availability by moderating daily hiking distances and/or increasing food intake.

Anal dysplasia and HIV shedding in ART-treated men.

OBJECTIVES: Anal human papillomavirus (HPV) infection is highly prevalent among men who have sex with men (MSM). HPV-associated anal dysplasia has been linked with anal HIV RNA shedding despite antiretroviral therapy (ART). Since mucosal HIV levels are a key determinant of sexual transmission of the virus, this would have important public health implications. Therefore, we assessed the association between anal dysplasia and HIV shedding in ART-treated MSM from Toronto, Canada. METHODS: In 54 HIV-infected men on effective ART, we assessed anal HIV RNA shedding by PCR, HPV infection by microsphere-based genotyping and anal dysplasia by high-resolution anoscopy. All participants were enrolled between May 2017 and October 2018. RESULTS: The median duration of ART at the time of study enrolment was 18 years, with most participants being on an integrase inhibitor-based ART regimen. Low-level anal HIV RNA shedding was present in 15/54 (27.8%) participants. Neither the detection of shedding nor the level of HIV RNA was associated with anal dysplasia, HPV infection or antiretroviral regimen. CONCLUSIONS: HPV-associated anal dysplasia was not associated with anal HIV RNA shedding in this relatively small cohort of men on effective ART. While anal HIV RNA was detected more often than anticipated, shedding was low level and unlikely to cause HIV transmission. However, the immunological drivers of anal HIV RNA shedding in ART-treated individuals may merit further study.

Sex-specific effects of dehydroepiandrosterone (DHEA) on bone mineral density and body composition: A pooled analysis of four clinical trials.

OBJECTIVE: Studies of dehydroepiandrosterone (DHEA) therapy in older adults suggest sex-specific effects on bone mineral density (BMD) and body composition, but the ability of a single study to reach this conclusion was limited. We evaluated the effects of DHEA on sex hormones, BMD, fat mass and fat-free mass in older women and men enrolled in four similar clinical trials. DESIGN: Pooled analyses of data from four double-blinded, randomized controlled trials. PARTICIPANTS: Women (n = 295) and men (n = 290) aged 55 years or older who took DHEA or placebo tablet daily for 12 months. MEASUREMENTS: Twelve-month changes in BMD, fat mass, fat-free mass and serum DHEA sulphate (DHEAS), (17)estradiol, testosterone and insulin-like growth factor-1 (IGF-1). RESULTS: Women on DHEA had increases (mean ± SD; all P < 0.001 vs placebo) in DHEAS (231 ± 164 µg/dL), testosterone (18.6 ± 20.9 µg/dL), (17)estradiol (8.7 ± 11.0 pg/mL) and IGF-1 (25.1 ± 52.3 ng/mL), and men had increases in DHEAS (269.0 ± 177 µg/dL; P < 0.01), (17)estradiol (4.8 ± 12.2 pg/m; P < 0.01) and IGF-1 (6.3 ± 41.4 ng/mL; P < 0.05). Women on DHEA had increases in lumbar spine (1.0% ± 3.4%) and trochanter (0.5% ± 3.8%) BMD and maintained total hip BMD (0.0% ± 2.8%); men had no BMD benefit and a decrease in fat mass (-0.4 ± 2.6 kg; all P < 0.01 vs placebo). CONCLUSIONS: Dehydroepiandrosterone therapy may be an effective approach for preserving bone and muscle mass in women. Key questions are (a) the extent to which longer duration DHEA can attenuate the loss of bone and muscle in women, and (b) whether DHEA has a more favourable benefit-to-risk profile for women than oestrogen therapy.

Short-Term Mediterranean Diet Improves Endurance Exercise Performance: A Randomized-Sequence Crossover Trial.

Objective: Healthful dietary patterns have constituents that are known to improve exercise performance, such as antioxidants, nitrates, and alkalizing effects. However, ergogenic effects of such diets have not been evaluated. We hypothesized that a short-term Mediterranean diet results in better exercise performance, as compared to a typical Western diet. Methods: Eleven recreationally active women (n = 7) and men (n = 4) (body mass index, 24.6 ± 3.2 kg/m2; age 28 ± 3 years) were studied in a randomized-sequence crossover study, in which they underwent exercise performance testing on one occasion after 4 days of a Mediterranean diet and on another occasion after 4 days of a Western diet. A 9- to 16-day washout period separated the two trials. Endurance exercise performance was evaluated with a 5-km treadmill time trial. Anaerobic exercise performance tests included a Wingate cycle test, a vertical jump test, and hand grip dynamometry. Results: Five-kilometer run time was 6% ± 3% shorter (faster) in the Mediterranean diet trial than in the Western diet trial (27.09 ± 3.55 vs 28.59 ± 3.21 minutes; p = 0.030) despite similar heart rates (160 ± 5 vs 160 ± 4 beats/min; p = 0.941) and ratings of perceived exertion (14.6 ± 0.5 vs 15.0 ± 0.5; p = 0.356). No differences between the diet conditions were observed for anaerobic exercise tests, including peak and mean power from the Wingate test (both p ≥ 0.05), the vertical jump test (p = 0.19), and the hand grip strength test (p = 0.69). Conclusions: Our findings extend existing evidence of the health benefits of the Mediterranean diet by showing that this diet is also effective for improving endurance exercise performance in as little as 4 days. Further studies are warranted to determine whether a longer-term Mediterranean diet provides greater benefits and whether it might also be beneficial for anaerobic exercise performance and muscle strength and power.

ENU-induced mutation in the DNA-binding domain of KLF3 reveals important roles for KLF3 in cardiovascular development and function in mice.

KLF3 is a Krüppel family zinc finger transcription factor with widespread tissue expression and no previously known role in heart development. In a screen for dominant mutations affecting cardiovascular function in N-ethyl-N-nitrosourea (ENU) mutagenized mice, we identified a missense mutation in the Klf3 gene that caused aortic valvular stenosis and partially penetrant perinatal lethality in heterozygotes. All homozygotes died as embryos. In the first of three zinc fingers, a point mutation changed a highly conserved histidine at amino acid 275 to arginine (Klf3(H275R) ). This change impaired binding of the mutant protein to KLF3's canonical DNA binding sequence. Heterozygous Klf3(H275R) mutants that died as neonates had marked biventricular cardiac hypertrophy with diminished cardiac chambers. Adult survivors exhibited hypotension, cardiac hypertrophy with enlarged cardiac chambers, and aortic valvular stenosis. A dominant negative effect on protein function was inferred by the similarity in phenotype between heterozygous Klf3(H275R) mutants and homozygous Klf3 null mice. However, the existence of divergent traits suggested the involvement of additional interactions. We conclude that KLF3 plays diverse and important roles in cardiovascular development and function in mice, and that amino acid 275 is critical for normal KLF3 protein function. Future exploration of the KLF3 pathway provides a new avenue for investigating causative factors contributing to cardiovascular disorders in humans.

Investigation of an Outbreak of Variant Influenza A(H3N2) Virus Infection Associated With an Agricultural Fair-Ohio, August 2012.

BACKGROUND: In 2012, one third of cases in a multistate outbreak of variant influenza A(H3N2) virus ([H3N2]v) infection occurred in Ohio. We conducted an investigation of (H3N2)v cases associated with agricultural Fair A in Ohio. METHODS: We surveyed Fair A swine exhibitors and their household members. Confirmed cases had influenza-like illness (ILI) and a positive laboratory test for (H3N2)v, and probable cases had ILI. We calculated attack rates. We determined risk factors for infection, using multivariable log-binomial regression. RESULTS: We identified 20 confirmed and 94 probable cases associated with Fair A. Among 114 cases, the median age was 10 years, there were no hospitalizations or deaths, and 82% had swine exposure. In the exhibitor household cohort of 359 persons (83 households), we identified 6 confirmed cases (2%) and 40 probable cases (11%). An age of <10 years was a significant risk factor (P < .01) for illness. One instance of likely human-to-human transmission was identified. CONCLUSIONS: In this (H3N2)v outbreak, no evidence of sustained human-to-human (H3N2)v transmission was found. Our risk factor analysis contributed to the development of the recommendation that people at increased risk of influenza-associated complications, including children aged <5 years, avoid swine barns at fairs during the 2012 fair season.

Effects of Short-Term Docosahexaenoic Acid Supplementation on Markers of Inflammation after Eccentric Strength Exercise in Women.

The omega-3 fatty acid docosahexaenoic acid (DHA) has anti-inflammatory and anti-nociceptive (pain inhibiting) effects. Because strenuous exercise often results in local inflammation and pain, we hypothesized that DHA supplementation attenuates the rise in markers of local muscle inflammation and delayed onset muscle soreness (DOMS) that occur after eccentric strength exercise. Twenty-seven, healthy women (33 ± 2 y, BMI 23.1±1.0 kg·m(-2)) were randomized to receive 9d of 3000 mg/d DHA or placebo in a double-blind fashion. On day 7 of the supplementation period, the participants performed 4 sets of maximal-effort eccentric biceps curl exercise. Before and 48h after the eccentric exercise, markers of inflammation were measured including measures of muscle soreness (10-point visual analog pain scale, VAS), swelling (arm circumference), muscle stiffness (active and passive elbow extension), skin temperature, and salivary C-reactive protein (CRP) concentrations. As expected, muscle soreness and arm circumference increased while active and passive elbow extension decreased. The increase in soreness was 23% less in the DHA group (48h increase in VAS soreness ratings: 4.380.4 vs. 5.600.5, p=0.02). Furthermore, the number of subjects who were able to achieve full active elbow extension 48h after eccentric exercise was greater in the DHA group (71% vs. 15%, p = 0.006), indicating significantly less muscle stiffness. No between-group differences were observed for passive elbow extension (p = 0.78) or arm swelling (p = 0.75). Skin temperature and salivary CRP concentrations did not change from baseline to 48h after exercise in either group. These findings indicate that short-term DHA supplementation reduces exercise-induced muscle soreness and stiffness. Therefore, in addition to other health benefits that n-3 fatty acids have been associated with, DHA supplementation could be beneficial for improving tolerance to new and/or strenuous exercise programs and thereby might facilitate better training adaptations and exercise adherence. Key pointsSeven days of 3000 mg/day supplementation with algae-derived docosahexaenoic acid (DHA) attenuates the delayed onset muscle soreness and stiffness, and protects against the loss of joint range of motion that is caused by strenuous eccentric exercise.This benefit was observed in women, and supports the findings from other studies that were conducted on men or a combination of men and womenThe benefits from algae-derived DHA appear to be similar to those reported in other studies that used a combination of DHA and eicosapentaenoic acid (EPA) derived from fish oilThe findings of better recovery from strenuous exercise with DHA supplementation, paired with other research which demonstrated that DHA and EPA protect against chronic diseases suggest that DHA is an attractive optionThese findings have relevance to athletic populations, in that DHA would be expected to facilitate recovery and allow for better performance during training and competition. However, DHA supplementation might also benefit non-athletic populations, such as individuals starting new exercise programs and patient populations that are prone to muscle soreness (e.g. physical therapy patients).

Micronutrient Deficiencies in Patients With Heart Failure: Relationships With Body Mass Index and Age.

BACKGROUND: It is conceivable that lean patients (body mass index 18.5-24.9 kg/m(2)) with heart failure (HF) have low body weight due to low food consumption and that this may contribute to micronutrient deficiencies and to their poorer prognosis compared with overweight/obese patients. We hypothesized that lean patients have a greater number of inadequate micronutrient intakes (<50% of recommendations) than overweight/obese patients and that this also depends on age. METHODS AND RESULTS: Lean (n = 15) and overweight/obese (n = 49) patients underwent 24-hour diet and physical activity recall interviews. Inadequate essential micronutrient intakes were ubiquitous (intakes of 13 ± 1 of 27 micronutrients were inadequate) and did not depend on race, status, or access to supermarkets. Younger (40-64 y) lean patients had inadequate intakes of 20 ± 2 micronutrients, which was more than the other weight/age subgroups (all P < .01). Physical activity levels did not differ across weight and age groups. CONCLUSIONS: Patients with HF may be at risk of malnutrition due to numerous inadequate micronutrient intakes; younger lean patients may have an especially high risk. Future studies are needed to confirm these preliminary findings and to investigate the possibility that incorporating a micronutrient-dense meal plan will improve patient outcomes.

Dietary supplement use among participants of a databank and biorepository at a comprehensive cancer centre.

OBJECTIVE: We assessed the prevalence, patterns and predictors of dietary supplement use among participants of the databank and biorepository (DBBR) at a comprehensive cancer centre in western New York. DESIGN: Archived epidemiological questionnaire data were obtained from the DBBR at Roswell Park Cancer Institute. Descriptive statistics and logistic regression explored the prevalence, patterns and predictors of lifetime use of four common supplements (multivitamins, vitamin C, vitamin E and calcium) and use of multivitamins, sixteen single vitamins/minerals and eighteen herbal/specialty supplements within the previous 10 years. SETTING: Western New York, USA. SUBJECTS: DBBR participants (n 8096) enrolled between December 2003 and July 2012 were included in these analyses: 66.9 % (n 5418) with cancer, 65.6 % (n 5309) women, mean age for patients v. cancer-free controls 59.9 (SD 12.6) years and 50.7 (SD 15.4) years, respectively. RESULTS: Overall, 54.4 % of DBBR participants reported lifetime use of one or more supplements and 63.1 % reported use of one or more supplements within the previous 10 years (excluding multivitamins). Multivitamin use was high in this sample (lifetime: 64.1 %; 10 years: 71.3 %; current: 51.8 %). Supplementation was higher among cancer-free controls than cancer patients. Vitamin C, calcium and fish oil were the most common single vitamin, mineral and specialty product, respectively. CONCLUSIONS: A consistently high and increasing proportion of dietary supplement use over time remains clear. Supplementation is prevalent among cancer patients and may even be higher than predicted in cancer-free individuals. Further studies should assess the safety and efficacy of specific supplements in reducing disease risk.

Effects of dietary Acid load on exercise metabolism and anaerobic exercise performance.

Dietary acid load, quantified as the potential renal acid load (PRAL) of the diet, affects systemic pH and acid-base regulation. In a previous cross-sectional study, we reported that a low dietary PRAL (i.e. alkaline promoting diet) is associated with higher respiratory exchange ratio (RER) values during maximal exercise. The purpose of the present study was to confirm the previous findings with a short-term dietary intervention study. Additionally, we sought to determine if changes in PRAL affects submaximal exercise RER (as a reflection of substrate utilization) and anaerobic exercise performance. Subjects underwent a graded treadmill exercise test (GXT) to exhaustion and an anaerobic exercise performance test on two occasions, once after following a low-PRAL diet and on a separate occasion, after a high-PRAL diet. The diets were continued as long as needed to achieve an alkaline or acid fasted morning urine pH, respectively, with all being 4-9 days in duration. RER was measured during the GXT with indirect calorimetry. The anaerobic performance test was a running time-to-exhaustion test lasting 1-4 min. Maximal exercise RER was lower in the low-PRAL trial compared to the high-PRAL trial (1.10 ± 0.02 vs. 1.20 ± 0.05, p = 0.037). The low-PRAL diet also resulted in a 21% greater time to exhaustion during anaerobic exercise (2.56 ± 0.36 vs. 2.11 ± 0.31 sec, p = 0.044) and a strong tendency for lower RER values during submaximal exercise at 70% VO2max (0.88 ± 0.02 vs. 0.96 ± 0.04, p = 0.060). Contrary to our expectations, a short-term low-PRAL (alkaline promoting) diet resulted in lower RER values during maximal-intensity exercise. However, the low-PRAL diet also increased anaerobic exercise time to exhaustion and appears to have shifted submaximal exercise substrate utilization to favor lipid oxidation and spare carbohydrate, both of which would be considered favorable effects in the context of exercise performance. Key pointsShort-term (4-9 days) changes in the acid or alkaline promoting qualities of the diet, quantified as potential renal acid load (PRAL), alter systemic pH, as evidenced in the present study by changes in fasted morning urine pH. Low-PRAL (alkaline promoting) diets are characterized by high intakes of vegetables and fruits with limited consumption of meats, cheeses, and grains while high-PRAL diets are characterized by the opposite dietary pattern.An alkaline promoting (low-PRAL) diet increases anaerobic exercise performance, as evidenced by greater time-to-exhaustion during high-intensity treadmill running.Preliminary evidence suggests that an alkaline promoting (low-PRAL) diet increases lipid oxidation and may have a carbohydrate-sparing effect during submaximal endurance exercise, although further studies are needed.In contrast to what has been observed in response to habitual/long-term dietary patterns, a short-term low-PRAL diet does not increase maximal exercise respiratory exchange ratio and even appears to lower it. This suggests that short-term and long-term alterations in PRAL have different physiologic effects on this parameter.

Effects of oral sodium supplementation on indices of thermoregulation in trained, endurance athletes.

Guidelines recommend the consumption of sodium during exercise to replace losses in sweat; however, the effects of sodium on thermoregulation are less clear. To determine the effects of high-dose sodium supplementation on indices of thermoregulation and related outcomes, 11 endurance athletes participated in a double-blind, randomized-sequence, crossover study in which they underwent 2-hrs of endurance exercise at 60% heart rate reserve with 1800 mg of sodium supplementation (SS) during one trial and placebo (PL) during the other trial. A progressive intensity time-to-exhaustion test was performed after the 2-hr steady state exercise as an assessment of exercise performance. Sweat rate was calculated from changes in body weight, accounting for fluid intake and urinary losses. Ratings of perceived exertion (RPE) and heat stress were assessed using verbal numeric scales. Cardiovascular drift was determined from the rise in HR during the 2-hr steady state exercise test. Skin temperature was measured with an infrared thermometer. Dehydration occurred in both SS and PL trials, as evidenced by substantial weight loss (2.03 ± 0.43% and 2.27 ± 0.70%, respectively; p = 0.261 between trials). Sweat rate was 1015.53 ± 239.10 ml·hr(-1) during the SS trial and 1053.60±278.24 ml/hr during the PL trial, with no difference between trials (p = 0.459). Heat stress ratings indicated moderate heat stress ("warm/hot" ratings) but were not different between trials (p = 0.825). Time to exhaustion during the SS trial was 6.88 ± 3.88 minutes and during the PL trial averaged 6.96 ± 3.61 minutes, but did not differ between trials (p = 0.919). Cardiovascular drift, skin temperature, and RPE did not differ between trials (all p > 0.05). High-dose sodium supplementation does not appear to impact thermoregulation, cardiovascular drift, or physical performance in trained, endurance athletes. However, in light of the possibility that high sodium intakes might have other adverse effects, such as hypertension, it is our recommendation that athletes interpret professional recommendations for sodium needs during exercise with caution. Key pointsBased on current professional recommendations to replace sodium losses in sweat during exercise, some endurance athletes consume salt or other electrolyte supplements containing sodium during training and competition, however the effects of sodium on thermoregulation are less clear.High-dose sodium supplementation does not appear to impact thermoregulation, cardiovascular drift, or physical performance in trained, endurance athletes.The possibility remains that high sodium intakes might have other adverse effects. It is our recommendation that athletes interpret professional recommendations for sodium needs during exercise with caution.

Benefits of caloric restriction for cardiometabolic health, including type 2 diabetes mellitus risk.

In the United States, life expectancy has markedly increased during the past century, and population ageing is expected to double within the next 25 years. The process of ageing in a population is associated with the development of chronic diseases, such as type 2 diabetes mellitus, that can be prevented, and even reversed, with the implementation of healthy lifestyle interventions. The evidence to date, consolidated by the numerous epidemiological studies and clinical trials conducted, suggests that caloric restriction is an effective nutritional intervention for preventing most of these age-related conditions. At a metabolic level, caloric restriction with adequate nutrition has been shown to improve insulin sensitivity, reduce fasting glucose and insulin concentration and prevent obesity, type 2 diabetes, hypertension and chronic inflammation. The purpose of this article is to review current knowledge of the metabolic and clinical implications of caloric restriction with adequate nutrition for the prevention of type 2 diabetes and cardiovascular disease.

Zinc deficiency-associated dermatitis in infants during a nationwide shortage of injectable zinc - Washington, DC, and Houston, Texas, 2012-2013.

Injectable zinc, a vital component of parenteral nutrition (PN) formulations, has been in short supply in the United States since late 2012. In December 2012, three premature infants with cholestasis hospitalized in Washington, DC, experienced erosive dermatitis in the diaper area and blisters on their extremities, a condition that can be associated with zinc deficiency. All three infants were receiving PN because they had extreme cholestasis and were unable to be fed by mouth or tube. The PN administered to each infant was zinc deficient. Injectable zinc normally is added to PN for premature or medically compromised infants (e.g., those with cholestasis) by the hospital pharmacy because the amount of zinc needed by each patient differs; however, the pharmacy had run out of injectable zinc. No alternatives were available; other preparations of parenteral trace elements either contained insufficient zinc to meet infants' requirements or had the potential to cause trace element toxicity in infants with cholestasis (2). The dermatitis of one infant resolved after the patient was able to take nutrition by mouth. The other two infants were found to have low serum zinc levels. In January 2013, CDC was notified of four additional cases of zinc deficiency among infants with cholestasis who received zinc-deficient PN in a hospital in Houston, Texas. In collaboration with the Food and Drug Administration (FDA), the two hospitals obtained emergency shipments of injectable zinc. No additional cases were reported. Current injectable zinc supplies have been increasing as FDA collaborates with pharmaceutical companies to import emergency supplies. FDA is working to establish temporary backup sources should future shortages occur.