Miracle-dz/UniFAR-FTUs huggingface dataset:
Influence of high-carbohydrate mixed meals with different glycemic indexes on substrate utilization during subsequent exercise in women.

BACKGROUND Few data exist on the metabolic responses to mixed meals with different glycemic indexes and their effects on substrate metabolism during exercise in women. OBJECTIVE We examined the effects of preexercise mixed meals providing carbohydrates with high (HGI) or low glycemic index (LGI) on substrate utilization during rest and exercise in women. DESIGN Eight healthy, active, eumenorrheic women [aged 18.6 +/- 0.9 y; body mass: 59.9 +/- 7.1 kg; maximal oxygen uptake (VO(2)max): 48.7 +/- 1.1 mL . kg(-1) . min(-1)] completed 2 trials. On each occasion, subjects were provided with a test breakfast 3 h before performing a 60-min run at 65% VO(2)max on a motorized treadmill. Both breakfasts provided 2 g carbohydrate/kg body mass and were isoenergetic. The calculated GIs of the meals were 78 (HGI) and 44 (LGI). RESULTS Peak plasma glucose and serum insulin concentrations were greater after the HGI breakfast than after the LGI breakfast (P < 0.05). No significant differences in substrate oxidation were reported throughout the postprandial period. During exercise, the estimated rate of fat oxidation was greater in the LGI trial than in the HGI trial (P < 0.05). Similarly, plasma free fatty acid and glycerol concentrations were higher throughout exercise in the LGI trial (P < 0.05). No significant differences in plasma glucose or serum insulin were observed during exercise. CONCLUSION Altering the GI of the carbohydrate within a meal significantly changes the postprandial hyperglycemic and hyperinsulinemic responses in women. A LGI preexercise meal resulted in a higher rate of fat oxidation during exercise than did an HGI meal.
Comparison of isotope dilution with bioimpedance spectroscopy and anthropometry for assessment of body composition in asymptomatic HIV-infected and HIV-uninfected breastfeeding mothers.

BACKGROUND The effect of breastfeeding on the nutrition of HIV-infected (HIV+) mothers is unknown. Simple, valid methods are needed for body-composition assessment of HIV+ women. OBJECTIVE We compared the ability of bioimpedance spectroscopy (BIS) and anthropometry with that of isotope dilution (2H2O) to measure fat-free mass (FFM) and fat mass (FM) in HIV+ and HIV-uninfected (HIV-) breastfeeding South African mothers. DESIGN Total body water (TBW) content of 68 lactating mothers (20 HIV+, 48 HIV-) was measured 10 wk after delivery by using BIS and 2H2O to measure FFM and FM. Anthropometric measurements included body mass index (BMI; in kg/m2), midupper arm circumference (MUAC), and 4 skinfold thicknesses. RESULTS TBW, FFM, and FM measurements determined by BIS were correlated with 2H2O measurements in HIV+ (r = 0.664, 0.621, and 0.872, respectively; P < 0.01) and HIV- (r = 0.876, 0.868, and 0.932, respectively; P < 0.001) mothers. TBW measured by BIS was greater than that measured by the 2H2O method in both HIV+ (1.8 L) and HIV- (1.5 L) women; FM or FFM did not differ significantly by method. BMI, MUAC, and all skinfold-thickness measurements correlated strongly (r > 0.62, P < 0.001) with FM measured by 2H2O in both groups. BMI and MUAC correlated (r > 0.64, P < 0.001) with FFM in HIV- mothers but not in HIV+ mothers. CONCLUSIONS In HIV+ and HIV- breastfeeding mothers, BIS provides an estimate of body composition comparable to that obtained with the 2H2O method. BMI and MUAC are useful in predicting FM in both groups but are not valid measures of FFM in HIV+ mothers.
Detection of Mycoplasma spp., herpesviruses, topiviruses, and ferlaviruses in samples from chelonians in Europe

We tested samples from 1,015 chelonians in Europe for Mycoplasma spp. , herpesviruses, ranaviruses, picornaviruses, and ferlaviruses by PCR. Mycoplasma spp. were detected in 42.1% and herpesviruses were detected in 8.0% of tested chelonians. Differentiation of the herpesviruses revealed that 46.9% of the detected chelonian viruses were testudinid herpesvirus 1 (TeHV-1) and 54.3% were TeHV-3, including co-detections of TeHV-1 and -3 in 3 tortoises. TeHV-4 was detected in a leopard tortoise (Stigmochelys pardalis), and a herpesvirus that could not be further characterized was found in a pond slider (Trachemys scripta). Picornaviruses (topiviruses) were detected in 2.2% of the tested animals; ferlaviruses were found in 0.6%; no ranaviruses were detected in any of the animals tested. Mycoplasma spp. were detected significantly more often in Horsfield’s tortoises (Testudo horsfieldii), leopard tortoises, and Indian star tortoises (Geochelone elegans) than in other species. Horsfield’s tortoises were also significantly more often positive for TeHV-1. Mycoplasma and TeHV-1 were co-detected in 3.0%, and mycoplasma and TeHV-3 in 2.3%. The TeHV-4–positive tortoise was also positive for mycoplasma. Mycoplasma and picornaviruses were co-detected in 1.2% of the tortoises. A spur-thighed tortoise (Testudo graeca) was positive for mycoplasma and a ferlavirus. In some cases, >2 pathogens were detected. A significant correlation between mycoplasma and herpesvirus detection was found. Of all tested animals, 47.6% were positive for at least one pathogen, demonstrating the importance of pathogen detection in captive chelonians.
Dietary acrylamide intake and the risk of renal cell, bladder, and prostate cancer.

BACKGROUND Acrylamide, a probable human carcinogen, was recently detected in various heat-treated carbohydrate-rich foods. Epidemiologic studies on the relation with cancer have been few and largely negative. OBJECTIVE We aimed to prospectively examine the association between dietary acrylamide intake and renal cell, bladder, and prostate cancers. DESIGN The Netherlands Cohort Study on diet and cancer includes 120,852 men and women aged 55-69 y. At baseline (1986), a random subcohort of 5000 participants was selected for a case-cohort analysis approach using Cox proportional hazards analysis. Acrylamide intake was assessed with a food-frequency questionnaire at baseline and was based on chemical analysis of all relevant Dutch foods. RESULTS After 13.3 y of follow-up, 339, 1210, and 2246 cases of renal cell, bladder, and prostate cancer, respectively, were available for analysis. Compared with the lowest quintile of acrylamide intake (mean intake: 9.5 microg/d), multivariable-adjusted hazard rates for renal cell, bladder, and prostate cancer in the highest quintile (mean intake: 40.8 microg/d) were 1.59 (95% CI: 1.09, 2.30; P for trend = 0.04), 0.91 (95% CI: 0.73, 1.15; P for trend = 0.60), and 1.06 (95% CI: 0.87, 1.30; P for trend = 0.69), respectively. There was an inverse nonsignificant trend for advanced prostate cancer in never smokers. CONCLUSIONS We found some indications for a positive association between dietary acrylamide and renal cell cancer risk. There were no positive associations with bladder and prostate cancer risk.
Essential fatty acid composition of plasma phospholipids and birth weight: a study in term neonates.

BACKGROUND Essential fatty acids (EFAs) in umbilical cord blood samples are associated with attained birth weight in premature infants and low-birth-weight neonates. OBJECTIVE The objective was to investigate relations between the EFA composition of cord and maternal plasma phospholipids and birth weight in term neonates. DESIGN This was a cross-sectional study in 627 singletons born at term. The plasma phospholipid EFA composition of the mothers was determined by gas-liquid chromatography at study entry (< or = 16 wk gestation), at delivery, and in cord plasma at birth. Birth weights were normalized to SD scores. RESULTS In cord plasma, the dihomo-gamma-linolenic acid concentration was positively related to weight SD scores. Both arachidonic acid (AA) and docosahexaenoic acid (DHA) were negatively related to weight SD scores. EFA-status indicators showed similar negative associations, whereas eicosatrienoic acid concentrations were positively related to neonatal size. In maternal plasma, proportions of n-3 long-chain polyenes (LCPs) and n-6 LCPs decreased during pregnancy. Larger decreases in AA, DHA, n-3 LCP, and n-6 LCP fractions were observed in mothers of heavier babies. Higher concentrations of LCPs in maternal plasma were, however, not related to a larger infant size at birth. CONCLUSIONS A lower biochemical EFA status in umbilical cord plasma and a larger decrease in maternal plasma LCP concentrations are associated with a higher weight-for-gestational-age at birth in term neonates. Our findings do not support a growth-stimulating effect of AA or DHA; however, they do suggest that maternal-to-fetal transfer of EFAs might be a limiting factor in determining neonatal EFA status.
Evidence for genetic regulation of vitamin D status in twins with multiple sclerosis23

Background: Multiple sclerosis (MS) risk is determined by both genes and environment. One of the most striking features of MS is its geographic distribution, particularly the pattern of high MS frequency in areas with low sunlight exposure, the main inducer of vitamin D synthesis. Recent epidemiologic, experimental, and clinical evidence support an effect for low environmental supplies of vitamin D in mediating an increased susceptibility to MS. Objectives: We 1) examined the association of serum 25-hydroxy-vitaminD [25(OH)D] concentrations and MS status and 2) assessed the genetic contribution to serum 25(OH)D concentrations and tested for its association with genetic variants in 2 candidate genes [vitamin D receptor and 1-α-hydroxylase (CYP27B1)]. Design: We used a twin study approach, comprising adult pairs identified from the longitudinal population-based Canadian Collaborative Project on Genetic Susceptibility to MS. Monozygotic (MZ; n = 40) and dizygotic (DZ; n = 59) pairs, both concordant and discordant for MS, were studied. End-of-winter serum 25(OH)D concentrations were measured by radioimmunoassay, and genotypes were assessed by single nucleotide polymorphism (SNP) assay. Results: Serum concentrations of 25(OH)D were highly correlated in MS-concordant pairs (r = 0.83, P < 0.001), but they were not significantly associated with having the disease (P = 0.4) when analyzed by logistic regression. Intraclass correlation for 25(OH)D concentration was significantly greater in MZ pairs (MZ, r: 0.71 > DZ r: 0.32, P = 0.006). Significant associations of 2 CYP27B1 SNP variants and 25(OH)D concentrations were observed. Conclusion: The findings indicate important genetic influences on regulation of seasonal circulating 25(OH)D concentrations in MS twins.
miRNA-1246 induces pro-inflammatory responses in mesenchymal stem/stromal cells by regulating PKA and PP2A

The tumor microenvironment (TME) has an impact on breast cancer progression by creating a pro-inflammatory milieu within the tumor. However, little is known about the roles of miRNAs in cells of the TME during this process. We identified six putative oncomiRs in a breast cancer dataset, all strongly correlating with poor overall patient survival. Out of the six candidates, miR-1246 was upregulated in aggressive breast cancer subtypes and expressed at highest levels in mesenchymal stem/stroma cells (MSCs). Functionally, miR-1246 led to a p65-dependent increase in transcription and release of pro-inflammatory mediators IL-6, CCL2 and CCL5 in MSCs, and increased NF-κB activity. The pro-inflammatory phenotype of miR-1246 in MSCs was independent of TNFα stimulations and mediated by direct targeting of the tumor-suppressors PRKAR1A and PPP2CB. In vitro recapitulation of the TME revealed increased Stat3 phosphorylation in breast epithelial (MCF10A) and cancer cells (SK-BR-3, MCF7, T47D) upon incubation with conditioned medium (CM) of MSCs overexpressing miR-1246. Additionally, this stimulation enhanced proliferation of MCF10A cells, increased migration of MDA-MB-231 cells and induced attraction of THP-1 monocytic cells. Our data shows that miR-1246 acts as both key-enhancer of pro-inflammatory responses in MSCs and putative oncomiR in breast cancer, suggesting its influence on cancer-related inflammation and breast cancer progression.
The difficulties with vitamin B12

A 22-year-old woman presented with progressive sensory ataxia and optic neuropathy. Previous investigation by her general practitioner had found a low serum vitamin B12, which had been corrected with oral supplementation. Neurological investigations showed raised plasma homocysteine and methylmalonic acid towards the upper limit of normal with a low serum vitamin B12. MRI showed an extensive cord lesion in keeping with subacute combined degeneration of the spinal cord. We treated her with high dose parenteral vitamin B12 and she has made a partial recovery. We discuss the management of patients who present with neurological manifestations of vitamin B12 deficiency; highlighting the fact that parenteral replacement is needed in such cases, even if the serum vitamin B12 level appears to be normal. We also discuss ancillary investigations that should be performed in patients with suspected vitamin B12 deficiency.
Mechanisms and kinetics of uptake and efflux of L-methionine in an intestinal epithelial model (Caco-2).

Mechanism and kinetics of uptake and efflux of L-methionine in a human intestinal epithelial model system (Caco-2) were studied to understand the transcellular transport process and to determine its rate-limiting step. The kinetic studies indicated that uptakes from both the apical and basolateral sides were saturable [for apical uptake: Km = 0.96 mmol/L, maximum flux = 673 pmol/(min.cm2); for basolateral uptake: Km = 3.46 mmol/L, maximum flux = 3480 pmol/(min.cm2)], whereas the efflux from these two membranes was apparently linear for intracellular concentrations < 6.5 mmol/L [for apical efflux, the apparent first-order rate constant = 1.01 x 10(-4) cm/min; for basolateral efflux, the rate constant = 1.78 x 10(-4) cm/min]. The results of inhibition studies indicate the apical uptake is partially active and Na(+)-dependent via a combination of amino acid transport systems B0,+ and ASC, which is somewhat different from the less energy- and Na(+)-dependent basolateral uptake. The basolateral uptake is also more dependent on system L and exhibits high counter-exchange capability. Finally, the rate-limiting step in the apical to basolateral transport of methionine is determined to be the basolateral efflux.
Immunomodulator effect of topical zinc oxide application in tuberculin skin test

OBJECTIVE: We aimed to evaluate the sensitivity of tuberculin skintest (purified protein derivative-PPD) by topical zinc application on test site to improve diagnostic reliability. METHODS: We performed this study in 100 children aged 6–14 years, and plasma zinc levels were analyzed after 10–12 hours fasting. After PPD, we applied 40% zinc oxide cream on one forearm and placebo on the other forearm. PPD indurations were measured 72 hours later. RESULTS: In this study, 26% of the children showed increases in PPD induration following local zinc applications. There was no correlation between indurations size and serum zinc levels. CONCLUSION: We concluded that topical zinc cream application can enhance sensitivity of tuberculin reactivityin the diagnosis of tuberculosis.
Tofacitinib Therapy for Rheumatoid Arthritis: A Direct Comparison Study between Biologic-naïve and Experienced Patients

Objective This study was designed to directly compare the outcomes of tofacitinib therapy for methotrexate-refractory rheumatoid arthritis (RA) between biologic-naïve patients and patients who had experienced an inadequate response to biological agents. Methods We prospectively enrolled and followed 113 patients who had a high or moderate clinical disease activity index (CDAI) (36 biologic-naïve patients and 77 biologic-experienced patients). Patients received 5 mg of tofacitinib twice daily. Effectiveness and adverse events were examined at month 6 of treatment. Results At month 6, 65 patients (57.5%) reached CDAI50, which is defined as achieving ≥50% improvement. The number of previous biological agents was twice as high in CDAI50 non-responders as in responders (2.2 versus 1.1, p＜0.001), but there was no significant difference in the type of previous agents or the reason for discontinuation. According to a multivariate logistic regression analysis, the previous use of biological agents [odds ratio (OR) 4.48, p=0.002] and the concurrent use of prednisolone (OR 2.40, p=0.047) were associated with a failure to achieve a CDAI 50 response. Biologic-naïve patients were more likely to achieve CDAI50 than biologic-experienced patients (80.6% versus 46.8%, p=0.001). Mean CDAI values were higher in biologic-experienced patients (11.4 versus 4.8, p=0.001), and remission rates were higher in biologic-naïve patients (41.7% versus 11.7%, p=0.001). Biologic-naïve patients more rapidly achieved remission. Rates of discontinuation resulting from adverse events were similar in both groups. Conclusion Although tofacitinib can provide an effective treatment option for intractable RA patients, its impact on outcomes is lower in patients with previous biologic failure.
Pexophagy is responsible for 65% of cases of peroxisome biogenesis disorders

ABSTRACT Peroxisome biogenesis disorders (PBDs) is a group of diseases caused by mutations in one of the peroxins, proteins responsible for biogenesis of the peroxisomes. In recent years, it became clear that many peroxins (e.g., PEX3 and PEX14) play additional roles in peroxisome homeostasis (such as promoting autophagic degradation of peroxisomes or pexophagy), which are often opposite to their originally established functions in peroxisome formation and maintenance. Even more interesting, the peroxins that make up the peroxisomal AAA ATPase complex (AAA-complex) in yeast (Pex1, Pex6 and Pex15) or mammals (PEX1, PEX6, PEX26) are responsible for the downregulation of pexophagy. Moreover, this might be even their primary role in human: to prevent pexophagy by removing from the peroxisomal membrane the ubiquitinated peroxisomal matrix protein import receptor, Ub-PEX5, which is also a signal for the Ub-binding pexophagy receptor, NBR1. Remarkably, the peroxisomes rescued from pexophagy by autophagic inhibitors in PEX1G843D (the most common PBD mutation) cells are able to import matrix proteins and improve their biochemical function suggesting that the AAA-complex per se is not essential for the protein import function in human. This paradigm-shifting discovery published in the current issue of Autophagy has raised hope for up to 65% of all PBD patients with various deficiencies in the AAA-complex. Recognizing PEX1, PEX6 and PEX26 as pexophagy suppressors will allow treating these patients with a new range of tools designed to target mammalian pexophagy.
Effect of zinc on the treatment of Plasmodium falciparum malaria in children: a randomized controlled trial.

BACKGROUND Zinc supplementation in young children has been associated with reductions in the incidence and severity of diarrheal diseases, acute respiratory infections, and malaria. OBJECTIVE The objective was to evaluate the potential role of zinc as an adjunct in the treatment of acute, uncomplicated falciparum malaria; a multicenter, double-blind, randomized placebo-controlled clinical trial was undertaken. DESIGN Children (n = 1087) aged 6 mo to 5 y were enrolled at sites in Ecuador, Ghana, Tanzania, Uganda, and Zambia. Children with fever and >or=2000 asexual forms of Plasmodium falciparum/ micro L in a thick blood smear received chloroquine and were randomly assigned to receive zinc (20 mg/d for infants, 40 mg/d for older children) or placebo for 4 d. RESULTS There was no effect of zinc on the median time to reduction of fever (zinc group: 24.2 h; placebo group: 24.0 h; P = 0.37), a >or=75% reduction in parasitemia from baseline in the first 72 h in 73.4% of the zinc group and in 77.6% of the placebo group (P = 0.11), and no significant change in hemoglobin concentration during the 3-d period of hospitalization and the 4 wk of follow-up. Mean plasma zinc concentrations were low in all children at baseline (zinc group: 8.54 +/- 3.93 micro mol/L; placebo group: 8.34 +/- 3.25 micro mol/L), but children who received zinc supplementation had higher plasma zinc concentrations at 72 h than did those who received placebo (10.95 +/- 3.63 compared with 10.16 +/- 3.25 micro mol/L, P < 0.001). CONCLUSION Zinc does not appear to provide a beneficial effect in the treatment of acute, uncomplicated falciparum malaria in preschool children.
Household exposure to passive cigarette smoking and serum micronutrient concentrations.

BACKGROUND The associations observed between passive smoking and adverse health outcomes have generated controversy. In part, this could be because the diets of passive smokers, like those of active smokers, differ from those of persons who are not exposed to cigarette smoke, especially with regard to antioxidants. OBJECTIVE Our objective was to assess the relation between household exposure to passive smoking and serum concentrations of retinol, tocopherols, and carotenoids. DESIGN A cross-sectional study was conducted in Washington County, MD, to compare exposure to passive smoking at home, recorded in a private census of county residents in 1975, with micronutrient concentrations assayed in serum collected in 1974. This comparison was possible for 1590 control subjects in nested case-control studies conducted between 1986 and 1998. RESULTS Among persons who were not current smokers, those who lived with smokers tended to have lower serum total carotenoid, alpha-carotene, ss-carotene, and cryptoxanthin concentrations than did those who lived in households with no smokers. There was little evidence that exposure to passive smoking was associated with reduced serum concentrations of lutein and zeaxanthin, lycopene, retinol, alpha-tocopherol, or gamma-tocopherol. CONCLUSIONS Among nonsmokers, exposure to passive smoking tended to be associated with lower serum concentrations of the carotenoids most strongly associated with active smoking (total carotenoids, alpha-carotene, ss-carotene, and cryptoxanthin). The associations were weaker for passive smoking than for active smoking. The consistency of the associations observed for active and passive smoking indicates that exposure to passive smoking may result in decreased circulating concentrations of selected micronutrients.
Enhancing Neurosurgical Education in Low- and Middle-income Countries: Current Methods and New Advances

Low- and middle-income countries (LMICs) face a critical shortage of basic surgical services. Adequate neurosurgical services can have a far-reaching positive impact on society’s health care and, consequently, the economic development in LMICs. Yet surgery, and specifically neurosurgery has been a long neglected sector of global health. This article reviews the current efforts to enhance neurosurgery education in LMICs and outlines ongoing approaches for improvement. In addition, we introduce the concept of a sustainable and cost-effective model to enhance neurosurgical resources in LMICs and describe the process and methods of online curriculum development.