Miracle-dz/UniFAR-FTUs huggingface dataset:
Dairy products do not lead to alterations in body weight or fat mass in young women in a 1-y intervention.

BACKGROUND Previous results suggested that increased intake of dairy calcium is associated with reduced weight and fat mass. OBJECTIVE The purpose of this study was to determine whether long-term increases in consumption of dairy calcium alter body weight and fat mass in young, healthy women. DESIGN We used a randomized, 1-y intervention for dairy calcium. Subjects were 155 young (aged 18-30 y), healthy, normal-weight women with intake of dietary calcium < 800 mg/d and energy intake </= 2200 kcal/d. Women were randomly assigned to 1 of 3 groups: 1) control: continue established dietary intake; 2) medium dairy: substitute dairy products to achieve intake of calcium of approximately 1000-1100 mg/d and maintain isocaloric intake; 3) high dairy: substitute dairy products to achieve intake of calcium of 1300-1400 mg/d and maintain isocaloric intake. The main outcome measures were 1-y changes in body weight (in kg) and fat mass (in kg). One hundred thirty-five women completed the trial. RESULTS Mean intakes of calcium during the intervention were 742.4 +/- 321.5, 1026.4 +/- 311.3, and 1131.29 +/- 337.2 mg/d for the control, medium-dairy, and high-dairy groups, respectively (P < 0.0001). No significant differences were observed in the mean 1-y change in body weight between the control, medium-dairy, and high-dairy groups (0.8 +/- 2.8, 0.7 +/- 3.0, and 1.5 +/- 4.1 kg, respectively; P = 0.45). No significant differences were observed in the mean 1-y change in fat mass between the control, medium-dairy, and high-dairy groups (-0.5 +/- 2.5, 0.3 +/- 2.7, and 0.5 +/- 3.5 kg, respectively; P = 0.26). CONCLUSION Increased intake of dairy products does not alter body weight or fat mass in young, healthy women over 1 y.
Effect of low-fat, fermented milk enriched with plant sterols on serum lipid profile and oxidative stress in moderate hypercholesterolemia.

BACKGROUND Plant sterol (PS)-enriched foods have been shown to reduce plasma LDL-cholesterol concentrations. In most studies, however, PSs were incorporated into food products of high fat content. OBJECTIVE We examined the effect of daily consumption of PS-supplemented low-fat fermented milk (FM) on the plasma lipid profile and on systemic oxidative stress in hypercholesterolemic subjects. DESIGN Hypercholesterolemic subjects (LDL-cholesterol concentrations >or=130 and <or= 190 mg/dL; n = 194) consumed 2 low-fat portions of FM in the same meal daily for 6 wk. Subjects were randomly assigned to 2 groups: low-fat FM enriched with 0.8 g PS ester per portion or control FM. Plasma concentrations of lipids, oxidized LDL, beta-carotene, beta-sitosterol, campesterol, and high-sensitivity C-reactive protein were measured during the trial. RESULTS Plasma LDL-cholesterol concentrations were reduced by 9.5% and 7.8% after 3 and 6 wk, respectively, in the 1.6-g/d PS group compared with the control group, whereas plasma triacylglycerol and HDL-cholesterol concentrations were not significantly affected. In addition, there were no significant changes in serum beta-carotene on normalization to LDL cholesterol during the study period in both groups, whereas plasma concentrations of oxidized LDL were reduced significantly in the PS group compared with the control group (-1.73 compared with 1.40 U/L, respectively; P < 0.05). Plasma sitosterol concentrations were increased by 35% (P < 0.001 compared with control); however, campesterol concentrations did not change during the study period. CONCLUSION Daily consumption of 1.6 g PS in low-fat FM efficiently lowers LDL cholesterol in subjects with moderate hypercholesterolemia without deleterious effects on biomarkers of oxidative stress.
Chronic hypoxia alters glucose utilization during GSH-dependent detoxication in rat small intestine.

We showed that hypoxia alters glutathione (GSH)-dependent detoxication and induces mucosal metabolic instability. To determine the impact of these changes and the role of reductant supply in intestinal lipid peroxide disposition, pair-fed (16 g/day) Sprague-Dawley rats were exposed to air (20.9% O2; n = 6) or 10% O2( n = 6) for 10 days. Jejunal and ileal everted sacs were exposed to 75 μM peroxidized fish oil with or without 10 mM glucose or 1 mM GSH. Peroxide transport was determined as the abluminal recovery of thiobarbituric acid-reactive substances. Peroxide recovery in hypoxic intestine was twice that in normoxic intestine. Addition of GSH and glucose did not affect peroxide recovery, indicating reduced intracellular GSH-dependent metabolism and enhanced output by the hypoxic intestine. Glucose uptake by normoxic and hypoxic intestine is similar, whereas its utilization for detoxication is decreased in hypoxic cells. Determination of NADPH supply indicates that decreased glucose availability for NADPH production during hypoxia impairs GSH disulfide reduction, compromises hydroperoxide metabolism, and increases peroxide output from hypoxic intestine.
Partial restoration of cAMP-stimulated CFTR chloride channel activity in ΔF508 cells by deoxyspergualin.

Deletion of the codon encoding phenylalanine 508 (ΔF508) is the most common mutation in cystic fibrosis (CF) and results in a trafficking defect. Mutant ΔF508-CF transmembrane conductance regulator (CFTR) protein retains functional activity, but the nascent protein is recognized as abnormal and, in consequence, is retained in the endoplasmic reticulum (ER) and degraded. It has been proposed that this retention in the ER is mediated, at least in part, by the cellular chaperones heat shock protein (HSP) 70 and calnexin. We have investigated the ability of deoxyspergualin (DSG), a compound known to compete effectively for binding with HSP70 and HSP90, to promote trafficking of ΔF508-CFTR to the cell membrane. We show that DSG treatment of immortalized human CF epithelial cells (ΔF508) and cells expressing recombinant ΔF508-CFTR partially restored cAMP-stimulated CFTR Cl-channel activity at the plasma membrane. Although there are several possible explanations for these results, one simple interpretation is that DSG may have altered the interaction between ΔF508-CFTR and its associated chaperones. If this is correct, agents capable of altering the normal functioning of cellular chaperones may provide yet another means of restoring CFTR Cl- channel activity to CF subjects harboring this class of mutations.
Risk of hepatitis C virus related hepatocellular carcinoma between subjects with spontaneous and treatment-induced viral clearance

Background/Aims Both spontaneous hepatitis C virus (HCV) clearance and the achievement of sustained virological response (SVR) by anti-viral therapy greatly reduce the incidence of hepatocellular carcinoma (HCC). The current study aimed to compare the risk of HCC between the two patient groups Methods A total of 313 subjects with spontaneous HCV clearance (SC) and 564 age- and sex-matched patients in the treatment-induced SVR group were enrolled for analysis. Results Nineteen (2.2%) of the 877 patients developed HCC during 6,963 person-years of follow-up. Fourteen (2.5%) SVR patients and 5 (1.6%) SC patients developed HCC (P=0.004). Cox regression analysis of factors predictive of HCC included SVR (versus SC: hazard ratio [HR]/ 95% confidence interval [CI]: 5.83/1.27-26.88), diabetes (HR/CI:3.41/1.21-9.58), and age (HR/CI: 1.07/1.01-1.14). Of the 564 SVR patients, eleven (5.9%) of the 187 patients with fibrosis stage 2-4 (F2-4) and 2 (0.9%) of the 226 patients with F01 developed HCC (P=0.01). Compared to SC subjects, only SVR patients with F2-4 (P<0.001) but not F0-1(P=0.60) had a higher risk of HCC development. Cox-regression analysis using liver fibrosis as a variable demonstrated that factors associated with HCC included SVR with F2-4 (versus SC: HR/CI: 10.06/2.20-45.98), diabetes (HR/CI:3.23/1.14-9.19), and age (HR/CI: 1.08 1.02-1.15). Conclusions Compared to subjects with spontaneous viral clearance, subjects with antiviral treatment-induced HCV viral clearance remain at high risk for HCC development, especially if they have significant hepatic fibrosis. These results may provide important information for decision-making regarding the prioritization of current direct antiviral agents in resource-limited countries.
Linear growth retardation in Zanzibari school children.

This paper describes the longitudinal changes in height and weight of children in school grades 1-3 on Pemba Island, Zanzibar, a poor rural population in which parasitic infections and anemia are highly prevalent. Heights and weights of children were measured at base line, and 6 and 12 mo later, and were compared with U.S. reference data. At base line, the prevalence of height-for-age Z-score < -2 rose from 14% in 7-y-old children to 83% in 13-y-old children. Prevalence of weight-for-age Z-score < -2 in children < 10 y was approximately 10% or less. Median 6-mo height increments for Pembian boys were around the 5th percentile at age 8 and around the 10th percentile from age 9 to 13 y. Height increments for girls improved from below the 25th percentile to above the median in this age range. Based on the longitudinal yearly gains observed, boys accumulate a height deficit of 11.9 cm and girls 8.5 cm, relative to the reference population. In multivariate analyses, a small part of the variability in growth increments was explained by ascariasis and anemia (for weight gain) and schistosomiasis (for height gain). A review of other growth data from rural African Bantu populations provides supporting evidence that stunting occurs in older as well as younger children. It has been controversial whether school-based health and nutrition interventions could induce catch-up growth in already stunted children. Our results suggest that appropriate interventions might actually prevent stunting in late childhood.
A Vaccine Platform against Arenaviruses Based on a Recombinant Hyperattenuated Mopeia Virus Expressing Heterologous Glycoproteins

ABSTRACT Several Old World and New World arenaviruses are responsible for severe endemic and epidemic hemorrhagic fevers, whereas other members of the Arenaviridae family are nonpathogenic. To date, no approved vaccines, antivirals, or specific treatments are available, except for Junín virus. However, protection of nonhuman primates against Lassa fever virus (LASV) is possible through the inoculation of the closely related but nonpathogenic Mopeia virus (MOPV) before challenge with LASV. We reasoned that this virus, modified by using reverse genetics, would represent the basis for the generation of a vaccine platform against LASV and other pathogenic arenaviruses. After showing evidence of exoribonuclease (ExoN) activity in NP of MOPV, we found that this activity was essential for multiplication in antigen-presenting cells. The introduction of multiple mutations in the ExoN site of MOPV NP generated a hyperattenuated strain (MOPVExoN6b) that is (i) genetically stable over passages, (ii) has increased immunogenic properties compared to those of MOPV, and (iii) still promotes a strong type I interferon (IFN) response. MOPVExoN6b was further modified to harbor the envelope glycoproteins of heterologous pathogenic arenaviruses, such as LASV or Lujo, Machupo, Guanarito, Chapare, or Sabia virus in order to broaden specific antigenicity while preserving the hyperattenuated characteristics of the parental strain. Our MOPV-based vaccine candidate for LASV, MOPEVACLASV, was used in a one-shot immunization assay in nonhuman primates and fully protected them from a lethal challenge with LASV. Thus, our hyperattenuated strain of MOPV constitutes a promising new live-attenuated vaccine platform to immunize against several, if not all, pathogenic arenaviruses. IMPORTANCE Arenaviruses are emerging pathogens transmitted to humans by rodents and responsible for endemic and epidemic hemorrhagic fevers of global concern. Nonspecific symptoms associated with the onset of infection make these viruses difficult to distinguish from other endemic pathogens. Moreover, the unavailability of rapid diagnosis in the field delays the identification of the virus and early care for treatment and favors spreading. The vaccination of exposed populations would be of great help to decrease morbidity and human-to-human transmission. Using reverse genetics, we generated a vaccine platform for pathogenic arenaviruses based on a modified and hyperattenuated strain of the nonpathogenic Mopeia virus and showed that the Lassa virus candidate fully protected nonhuman primates from a lethal challenge. These results showed that a rationally designed recombinant MOPV-based vaccine is safe, immunogenic, and efficacious in nonhuman primates.
Glucocorticoids have pleiotropic effects on small intestinal crypt cells.

Glucocorticoids have long been known to accelerate maturation of the intestinal tract, but the molecular mechanisms that account for their physiological function in the epithelium remain poorly characterized. Using rat intestinal epithelial cell lines (IEC-6, IEC-17, and IEC-18) as models, we have characterized glucocorticoid receptors in crypt cells and documented striking morphological, ultrastructural, and functional alterations induced by these hormones in intestinal cells. They include arrest of growth, formation of tight junctions, appearance of long, slender microvilli, reorganization of the endoplasmic reticulum and trans-Golgi network, and downregulation of the cell cycle regulatory proteins cyclin-dependent kinase 6 and p27Kip1. These effects are consistent with the activation or modulation of multiple genes important in the physiological function of absorptive villous cells but are probably not directly involved in the induction of cell differentiation.
Variants in the CYP2B6 3′UTR Alter In Vitro and In Vivo CYP2B6 Activity: Potential Role of MicroRNAs

CYP2B6*6 and CYP2B6*18 are the most clinically important variants causing reduced CYP2B6 protein expression and activity. However, these variants do not account for all variability in CYP2B6 activity. Emerging evidence has shown that genetic variants in the 3′UTR may explain variable drug response by altering microRNA regulation. Five 3′UTR variants were associated with significantly altered efavirenz AUC0‐48 (8‐OH‐EFV/EFV) ratios in healthy human volunteers. The rs70950385 (AG>CA) variant, predicted to create a microRNA binding site for miR‐1275, was associated with a 33% decreased CYP2B6 activity among normal metabolizers (AG/AG vs. CA/CA (P < 0.05)). In vitro luciferase assays were used to confirm that the CA on the variant allele created a microRNA binding site causing an 11.3% decrease in activity compared to the AG allele when treated with miR‐1275 (P = 0.0035). Our results show that a 3′UTR variant contributes to variability in CYP2B6 activity.
Influence of Mechanically Induced Damage on Durability and Service Life of Reinforced Concrete Structures

Concrete specimens have been exposed to direct tensile stress up to 85 % of the tensile strength. The damage induced into the composite structure of concrete by applied tensile load has been quantified by measuring the porosity and determining a damage index. Both the porosity and the damage index increase with increasing applied tensile stress. Chloride penetration into undamaged and damaged concrete has been determined. It could be shown that during the initial phase of salt water absorption, capillary absorption is the dominant transport mechanism. Chloride is transported with the penetrating liquid into the pore system. Later the rate of capillary absorption becomes very slow and diffusion takes over the transport. For this reason during the first month of contact of the surface of concrete with salt solution the coefficient of capillary absorption is considered to describe penetration of chloride correctly. The coefficient of capillary absorption increases with increasing applied tensile load. At a later stage the rate of chloride penetration can be described by means of a diffusion coefficient. The diffusion coefficient also increases if the specimens have been loaded before the test. It is shown that chloride uptake of concrete is a complex process and further tests are necessary to provide a solid basis for prediction of service life of reinforced concrete structures in marine environment.
Curcumin restores glutathione-S-transferase activity for LNCaP prostate cancer cells

Prostate cancer is a leading cause of death in males aged fifty and over. Glutathione transferase (GST) activity is depressed in prostate cancer cells. The aim of this study was to assess GST reactivation in LNCaP prostate cancer cells treated with curcumin or 5-azacitidine (5-Aza) which is a known hypomethylation agent. GST activity was determined using monochlorobimane (MCB). Cell viability was assessed with resazurin (Vision blue TM) or 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-di-phenyltetrazolium- bromide (MTT). From the results, treatment with >5 μM of curcumin or 5-Aza for 3 or 6 days depressed LNCaP cell viability. The concentrations of curcumin leading to 50% reduction of LNCaP cell viability (IC50) was 10-25 μM or 2-3 μM for 3 days or 6 days of treatment, respectively. The IC50 with 5-Aza was 17-23 μM (3 days) or 50-52 μM (6 days). Combination treatment using curcumin and 5-Aza showed complimentary interactions affecting cell viability. Low levels of curcumin or 5-Aza had no effect on GST activity. By contrast, cytotoxic doses of curcumin or 5-Aza increased GST activity by 450-750 % (3days) or 161-2800 % (6days). In conclusion, GST reactivation was feasible but only when LNCaP prostate cancer cells were treated with cytotoxic doses of curcumin or 5-azacytidne.
Synthesis Under Microwave Irradiation and Molecular Docking of Some Novel Bioactive Thiadiazoles.

BACKGROUND A novel series of fused imidazole was prepared from the reaction of 2- bromoacetyl-3-phenyl-1,3,4-thiadiazole with various heterocyclic amines under microwave irradiation. The structures of all the novel products were elucidated based on the elemental analysis and spectral data. RESULTS In addition, the biological activity of the newly synthesized compounds was evaluated and the results obtained indicate their potency as anti-inflammatory, analgesic and anti- ulcer agents. CONCLUSION The binding mechanism of the most active compounds was studied using MOE to analyze the molecular interactions.
Tyrosine kinase inhibitors and antioxidants modulate NF-κB and NOS-II induction in retinal epithelial cells.

Bovine retinal pigmented epithelial (RPE) cells express an inducible nitric oxide synthase (NOS-II) after activation with interferon-γ (IFN-γ) and lipopolysaccharide (LPS). Experiments were performed to investigate the effects of tyrosine kinase inhibitors (genistein and herbimycin A) and antioxidants [pyrrolidine dithiocarbamate (PDTC) and butyl hydroxyanisol] on NOS-II induction. The LPS-IFN-γ-induced nitrite release was inhibited in a concentration-dependent manner by these compounds. Analysis by Northern blot showed that this inhibitory effect correlated with a decrease in NOS-II mRNA accumulation. Analysis by electrophoretic mobility shift assay of the activation of the transcription factor nuclear factor-κB (NF-κB) involved in NOS-II induction demonstrated that LPS alone or combined with IFN-γ induced NF-κB binding. NF-κB activation was not changed by the presence of tyrosine kinase inhibitors but was totally prevented by PDTC pretreatment. Immunocytochemistry experiments confirmed the reduction of the nuclear translocation of NF-κB only by PDTC. Our results demonstrated the existence in retinal pigmented epithelial cells of different intracellular signaling pathways in NOS-II induction, since tyrosine kinase inhibitors blocked NOS-II mRNA accumulation without inhibiting NF-κB activation. Furthermore, the LPS-IFN-γ-induced NOS-II mRNA accumulation was sensitive to cycloheximide, suggesting that, in addition to NF-κB, transcriptional factors that require new protein synthesis are involved in NOS-II induction.
Intestinal parasites increase the dietary lysine requirement in chronically undernourished Indian men.

BACKGROUND We previously used the 24-h indicator amino acid balance method to show that the lysine requirement in undernourished Indian men from low socioeconomic and unsanitary environments is approximately 50% higher than the mean requirement of 30 mg lysine. kg(-1). d(-1) in well-nourished men. OBJECTIVE It is possible that this higher lysine requirement in persons with chronic undernutrition is due to environmental influences, including the presence of intestinal parasites. We assessed this possibility by using 24-h indicator amino acid balance (with leucine) at both the "normal" requirement for lysine intake and the higher requirement, before and after successful treatment to eradicate intestinal parasites in affected, undernourished men. DESIGN Fourteen chronically undernourished men were studied before and after treatment for intestinal parasites, during each of two 7-d (6-d dietary adaptation plus 1-d tracer experiment) diet periods supplying either 30 (n = 7) or 45 (n = 7) mg lysine. kg(-1). d(-1) from an L-amino acid diet. Twenty-four-hour indicator amino acid balance was estimated on day 6 by [(13)C]leucine tracer infusion. RESULTS Before the parasite treatment, subjects were in neutral 24-h leucine balance at both lysine intakes. After the eradication of intestinal parasites, there was a significant (P < 0.001) improvement in 24-h leucine balances, which were positive at both lysine intakes. CONCLUSIONS On the basis of the 24-h indicator amino acid balance approach, it appears that intestinal infestation with parasites increases the requirement for lysine and that this may be one factor responsible for the higher lysine requirement observed in persons with chronic undernutrition.
The challenge of opt-outs from NHS data: a small-area perspective

One of the founding principles of the NHS is that it offers comprehensive, universal and free public health services at the point of delivery. As a result, NHS data provide a huge and invaluable resource of routinely collected primary (e.g. visits to GP practices) and secondary (e.g. hospital admissions, outpatient appointments, A&E attendances) healthcare data covering near-100% of the population of England. NHS Digital has the responsibility for collecting and publishing data and information from across the health and social care system in England and controls the dissemination of these data. Detailed analysis of NHS data by public health and research institutions has the potential to considerably improve health and social care in England. Data privacy and confidentiality of identifiable health data are a legal responsibility of the NHS, and a source of concern for patients. As illustrated by recent controversies and cyber-attacks,1,2 ensuring data security has become a growing technological challenge for the NHS, for example, with the move towards electronic health records. As per the NHS Constitution,3 patients have the right to request that their confidential information is not used beyond their own care and treatment. This right was formalized in January 2014 through an opt-out system, following a recommendation made by the National Data Guardian (NDG) for Health and Care, Dame Fiona Caldicott, in her 2013 report.4 A National Data Opt-out Programme is scheduled to replace the current two types of opt-outs from March 2018, following new recommendations made by the NDG in her Review of data security, consent and opt-outs published in 2016.5 Public health research, including disease surveillance, can contribute vital information for the direct care and treatment of patients,6,7 as well as broader issues related to population health,8 but many studies are no longer granted access to the full national health datasets held by NHS Digital. Our aim here is to comment, ahead of the launch of the new National Data Opt-out Programme, on the potential consequences of these non-random gaps in national health databases. This is particularly a concern for research that is currently unable to access complete health data, i.e. where opt-outs are upheld, such as, for example, small-area health studies of non-communicable diseases.9