Miracle-dz/UniFAR-FTUs huggingface dataset:
A Randomized Trial of High-Dose Vitamin D2 in Relapsing-remitting Multiple Sclerosis

Objective: Higher latitude, lower ultraviolet exposure, and lower serum 25-hydroxyvitamin D (25OHD) correlate with higher multiple sclerosis (MS) prevalence, relapse rate, and mortality. We therefore evaluated the effects of high-dose vitamin D2 (D2) in MS. Methods: Adults with clinically active relapsing-remitting MS (RRMS) were randomized to 6 months9 double-blind placebo-controlled high-dose vitamin D2, 6,000 IU capsules, dose adjusted empirically aiming for a serum 25OHD 130–175 nM. All received daily low-dose (1,000 IU) D2 to prevent deficiency. Brain MRIs were performed at baseline, 4, 5, and 6 months. Primary endpoints were the cumulative number of new gadolinium-enhancing lesions and change in the total volume of T2 lesions. Secondary endpoints were Expanded Disability Status Scale (EDSS) score and relapses. Results: Twenty-three people were randomized, of whom 19 were on established interferon or glatiramer acetate (Copaxone) treatment. Median 25OHD rose from 54 to 69 nM (low-dose D2) vs 59 to 120 nM (high-dose D2) ( p = 0.002). No significant treatment differences were detected in the primary MRI endpoints. Exit EDSS, after adjustment for entry EDSS, was higher following high-dose D2 than following low-dose D2 ( p = 0.05). There were 4 relapses with high-dose D2 vs none with low-dose D2 ( p = 0.04). Conclusion: We did not find a therapeutic advantage in RRMS for high-dose D2 over low-dose D2 supplementation. Classification of evidence: This study provides Class I evidence that high-dose vitamin D2 (targeting 25OHD 130–175 nM), compared to low-dose supplementation (1,000 IU/d), was not effective in reducing MRI lesions in patients with RRMS.
Mitochondrial specialization revealed by single muscle fiber proteomics: focus on the Krebs cycle

We have developed a highly sensitive mass spectrometry‐based proteomic workflow to examine the proteome of single muscle fibers. This study revealed significant differences in the mitochondrial proteome of the four major fiber types present in mouse skeletal muscle. Here, we focus on Krebs cycle enzymes and in particular on the differential distribution of the two mitochondrial isocitrate dehydrogenases, IDH2 and IDH3. Type 1/slow fibers contain high levels of IDH2 and relatively low levels of IDH3, whereas fast 2X and 2B fibers show an opposite expression pattern. The findings suggest that in skeletal muscle, IDH2 functions in the forward direction of the Krebs cycle and that substrate flux along the cycle occurs predominantly via IDH2 in type 1 fibers and via IDH3 in 2X and 2B fibers. IDH2‐mediated conversion of isocitrate to α‐ketoglutarate leads to the generation of NADPH, which is critical to buffering the H2O2 produced by the respiratory chain. Nicotinamide nucleotide transhydrogenase (NNT), the other major mito‐chondrial enzyme involved in NADPH generation, is also more abundant in type 1 fibers. We suggest that the continuously active type 1 fibers are endowed with a more efficient H2O2 scavenging capacity to cope with the higher levels of reactive oxygen species production.
Postoperative Validation of Bone-Anchored Implants in the Single-Sided Deafness Population

Objective The purpose of this study was to present objective and subjective outcomes on speech-in-noise testing as a predictor of patient performance after bone-anchored implant surgery in patients with single-sided deafness (SSD). Design Retrospective review of adult subjects who received bone-anchored implants for the indication of SSD comparing results on speech-in-noise measures in the unaided condition to postoperative aided condition using the patient’s external bone-anchored implant processor as a validation of device performance. Setting Tertiary referral center providing outpatient surgical and audiologic care. Patients Adult English speaking subjects with SSD who underwent bone-anchored implantation between 2005 and 2010. Intervention Subjects were evaluated with speech-in-noise measures in the sound field using a 90/270 speaker configuration in both the unaided and aided implant condition for validation of implant performance. Subjective benefit was evaluated using the Glasgow Hearing Aid Benefit Profile. Main Outcome Measures Outcome measures included signal-to-noise ratio (SNR) loss and word recognition ability in noise as measured using the QuickSIN and the Glasgow Hearing Aid Benefit Profile. Results A significant improvement in speech-in-noise measures was noted in the postoperative aided condition when compared with the unaided condition (Wilcoxon signed-rank test, p < 0.0001). Significant decrease in disability postoperatively also was observed (Wilcoxon signed-rank test, p < 0.001). Positive associations were observed for postoperative aided SNR loss and benefit, satisfaction, and use. Passing-Bablok regression analysis showed the preoperative and postoperative results to be statistically equivalent. Conclusion The results support the use of speech-in-noise measures as an accurate postimplantation assessment of overall benefit in patients with SSD. SNR loss is a good predictor of postoperative subjective benefit and satisfaction.
Tissue remodeling in periplaque regions of multiple sclerosis spinal cord lesions

Our knowledge of multiple sclerosis (MS) neuropathology has benefited from a number of studies that provided an in‐depth description of plaques and, more recently, diffuse alterations of the normal‐appearing white or grey matter. However, there have been few studies focusing on the periplaque regions surrounding demyelinated plaques, notably in MS spinal cords. In this context, the present study aimed to analyze the molecular immunopathology of periplaque demyelinated lesions (PDLs) in the spinal cord of patients with a progressive form of MS. To achieve this goal, the neuropathological features of PDLs were analyzed in postmortem tissues derived from the cervical spinal cord of 21 patients with primary or secondary progressive MS. We found that PDLs covered unexpectedly large areas of incomplete demyelination and were characterized by the superimposition of pro‐ and anti‐inflammatory molecular signatures. Accordingly, macrophages/microglia accumulated in PDLs but exhibited a poor phagocytic activity toward myelin debris. Interestingly, while genes of the oligodendrocyte lineage were consistently down‐regulated in PDLs, astrocyte‐related molecules such as aquaporin 4, connexin 43 and the glutamate transporter EAAT1, were significantly upregulated in PDLs at the mRNA and protein levels. Overall, our work indicates that in the spinal cord of patients with a progressive form of MS, a tissue remodeling process that is temporally remote from plaque development takes place in PDLs. We propose that in spinal cord PDLs, this process is supported by subtle alterations of astrocyte functions and by low‐grade inflammatory events that drive a slowly progressive loss of myelin and a failure of remyelination. GLIA 2014;62:1645–1658
A meta-analysis of police suicide rates: findings and issues.

Meta-analyses of police suicide rates and ratios to the comparison population were conducted using 101 samples from the literature. The large effect sizes (ES = .74) showed that suicide rates based on short time frames were significantly higher than for long time frames. There were regional differences such that rates in the Americas and Europe were higher than in the Caribbean and Asian regions. There were differences in rates between federal, regional, and municipal police forces. Issues researchers need to address include the use of long time frames; the reporting of more complete suicide statistics, including breakdowns by year, sex, and ethnic groups; and the rates for population comparison groups.
Incidence of bony outgrowths of the external ear canal in U.S. Navy divers.

Bony outgrowths of the temporal bone into the external ear canal are common in populations that participate in cold water activities. The incidence in professional divers is unknown. Eighty-seven U.S. Navy divers were interviewed and examined to determine the history of aquatic activity and degree of ear canal compromise. An age-matched control population of 42 non-divers without significant history of aquatic activities was also examined. The outgrowths, or exostoses, were found in 23 (26%) divers, and in no controls. Sixteen (70%) of the exostoses were minor, causing 10-20% narrowing of the auditory canal. The largest exostoses were found in divers with an extensive history of aquatic activities. The difference in total hours of aquatic activity was significant between divers and controls. The difference in total hours diving, as well as total time of all aquatic activities, was statistically significant between divers with exostoses and those divers without exostoses. The data confirm the relatively common incidence of this condition in a professional diving community.
Case-Control Pilot Study on Acute Diarrheal Disease in a Geographically Defined Pediatric Population in a Middle Income Country

Introduction Acute diarrheal disease (ADD) is a common cause of morbidity and mortality in children under 5 years of age. Understanding of the etiology of ADD is lacking in most low and middle income countries because reference laboratories detect limited number of pathogens. The objective of this study was to determine the feasibility to conduct a comprehensive case-control study to survey diarrheal pathogens among children with and without moderate-to-severe ADD. Materials and Methods Microbiology and molecular-based techniques were used to detect viral, bacterial, and parasitic enteropathogens. The study was conducted in Bucaramanga, Colombia, after Institutional Review Board approval was obtained. Results Ninety children less than 5 years of age were recruited after a written informed consent was obtained from parents or guardians. Forty-five subjects served as cases with ADD and 45 as controls. Thirty-six subjects out of 90 (40.0%) were positive for at least one enteropathogen, that is, 20 (44.4%) cases and 16 (35.5%) controls. Conclusions The three most common enteric pathogens were enteroaggregative E. coli (10.0%), Norovirus (6.7%), and Salmonella spp. (5.6%). The E. coli pathogens were 18.8% of all infections making them the most frequent pathogens. Half of ADD cases were negative for any pathogens.
Effect of larger ablation zone and transition zone on corneal optical aberrations after photorefractive keratectomy.

OBJECTIVE To evaluate the effects of photorefractive keratectomy on corneal optical aberrations using a 5.5-mm optical zone and a 7.0-mm transition zone. METHODS Videokeratographs of 72 eyes from 47 patients treated for low to moderate (1-9 diopters) myopia were obtained at the preoperative and 1-, 3-, 6-, 12-, and 18-month postoperative examinations. The videokeratoscopy data files were used to calculate the wavefront variance of the corneas for small (3-mm) and large (7-mm) pupils using a previously described method. RESULTS In general, all optical aberrations decreased postoperatively for 3-mm pupils and increased for 7-mm pupils compared with preoperative values. For 3-mm pupils, the 2 common optical aberrations (comalike [S(3)] and spherical-like [S(4)]) decreased postoperatively and never returned to preoperative values. For 7-mm pupils, however, comalike aberrations increased slightly and spherical-like aberrations increased by nearly an order of magnitude during the postoperative period. Similarly, for 3-mm pupils, the higher order S(5) and S(6) aberrations decreased throughout the postoperative period, with S(6) values showing an approximately 23-fold reduction at 12 and 18 months. For 7-mm pupils, S(5) and S(6) aberrations increased slightly, more so for S(5) (approximately 3-fold) than for S(6). Total wavefront aberrations decreased an average of 2.3 times postoperatively for 3-mm pupils, and increased significantly (P<.05) at all postoperative examinations for 7-mm pupils. Opening the pupil from 3 mm to 7 mm before surgery produced a 14-fold increase in total aberrations, whereas this same change produced an average 113-fold increase after photorefractive keratectomy. CONCLUSIONS Corneal optical aberrations after photorefractive keratectomy with a larger ablation zone and a transition zone are less pronounced and more physiologic than those associated with first-generation (5-mm) ablations with no transition zone. CLINICAL RELEVANCE Evaluating the postoperative corneal aberration structure will help us devise ways to minimize the wavefront aberrations of the eye through the creation of an ideal corneal first surface, thereby improving visual results for patients undergoing excimer laser ablations for refractive correction.
Factor analysis identifies subgroups of constipation.

AIM To determine whether distinct symptom groupings exist in a constipated population and whether such grouping might correlate with quantifiable pathophysiological measures of colonic dysfunction. METHODS One hundred and ninety-one patients presenting to a Gastroenterology clinic with constipation and 32 constipated patients responding to a newspaper advertisement completed a 53-item, wide-ranging self-report questionnaire. One hundred of these patients had colonic transit measured scintigraphically. Factor analysis determined whether constipation-related symptoms grouped into distinct aspects of symptomatology. Cluster analysis was used to determine whether individual patients naturally group into distinct subtypes. RESULTS Cluster analysis yielded a 4 cluster solution with the presence or absence of pain and laxative unresponsiveness providing the main descriptors. Amongst all clusters there was a considerable proportion of patients with demonstrable delayed colon transit, irritable bowel syndrome positive criteria and regular stool frequency. The majority of patients with these characteristics also reported regular laxative use. CONCLUSION Factor analysis identified four constipation subgroups, based on severity and laxative unresponsiveness, in a constipated population. However, clear stratification into clinically identifiable groups remains imprecise.
Hyporeactivity to interferon induction: characterization of a hyporeactive factor in the serum of encephalomyocarditis virus-infected mice

Mice infected with encephalomyocarditis virus develop a severe state of hyporeactivity to interferon induction. One mechanisms possibly responsibile for development of hyporesponsiveness in these animals is a circulating factor which can be detected in their serum 96 h after encephalomyocarditis virus infection (at the time of peak hyporeactivity in vivo). This report describes some of the physiocochemical characteristics of this serum hyporeactive factor (SHF). SHF is a protein with a molecular weight between 20,000 and 40,000 that was extremely labile at 56 C, losing greater than 90% of its biological activity in 8 min, but stable at 37 c for at least 4 h. Hyporeactive factor was also stable over a pH range of 2 to 11 for 48 h at 4 C. These results suggest that SHF is physicochemically similar to interferon. However, no interferon could be detected in the SHF preparation, and no loss in biological activity was observed when the serum factor was incubated with anti-interferon antibody, suggesting that they are separate substances.
Airways obstruction among older construction and trade workers at Department of Energy nuclear sites.

BACKGROUND A study of chronic obstructive pulmonary disease (COPD) among 7,579 current and former workers participating in medical screening programs at Department of Energy (DOE) nuclear weapons facilities through September 2008 was undertaken. METHODS Participants provided a detailed work and exposure history and underwent a respiratory examination that included a respiratory history, respiratory symptoms, a posterior-anterior (P-A) chest radiograph classified by International Labour Office (ILO) criteria, and spirometry. Statistical models were developed to generate group-level exposure estimates that were used in multivariate logistic regression analyses to explore the risk of COPD in relation to exposures to asbestos, silica, cement dust, welding, paints, solvents, and dusts/fumes from paint removal. Risk for COPD in the study population was compared to risk for COPD in the general US population as determined in National Health and Nutrition Examination Survey (NHANES III). RESULTS The age-standardized prevalence ratio of COPD among DOE workers compared to all NHANES III data was 1.3. Internal analyses found the odds ratio of COPD to range from 1.6 to 3.1 by trade after adjustment for age, race, sex, smoking, and duration of DOE employment. Statistically significant associations were observed for COPD and exposures to asbestos, silica, welding, cement dusts, and some tasks associated with exposures to paints, solvents, and removal of paints. CONCLUSIONS Our study of construction workers employed at DOE sites demonstrated increased COPD risk due to occupational exposures and was able to identify specific exposures increasing risk. This study provides additional support for prevention of both smoking and occupational exposures to reduce the burden of COPD among construction workers.
Analysis of Survival of Young and Old Aedes aegypti (Diptera: Culicidae) from Puerto Rico and Thailand

Abstract It generally is assumed that the daily probability of survival of wild adult mosquitoes is independent of age. To test this assumption we conducted mark-release-recapture studies in Puerto Rico and Thailand to determine if estimated daily survival rates between two different age cohorts of the dengue vector Aedes aegypti (L.) were the same. Survivorship was estimated with nonlinear regression analysis using bootstrapping to obtain estimates of errors. Initial recapture success of the younger cohort was greater than the older cohort at both locations. Our analysis revealed a significantly greater survival rate for the younger cohort of females in Puerto Rico, and no significant differences between age cohorts in Thailand. For comparison, a traditional approach for analyzing these type of data, linear regression of log-transformed captures over time (exponential model), was used to calculate the probability of daily survival based on slopes of linear regression lines for recaptured mosquitoes. With this method, the estimated daily survival rate of older females (13–23 d old) was significantly greater than survival of younger ones (3–13 d old) in Puerto Rico and Thailand. In addition, short-range movement of mosquitoes was observed in Puerto Rico; maximum dispersal distance detected was 79 m. Survival rates of adult Ae. aegypti may be age-dependent and nonlinear regression analysis is a sensitive approach for comparing patterns of mosquito survival based on mark, single release, multiple recapture data.
15-year prospective follow-up study of behavioral therapy in a large sample of inpatients with chronic tinnitus

Conclusion: The results of this study are in accordance with the assumption that cognitive-oriented therapy enabling the patient to live with tinnitus is of primary importance to enhance quality of life. Background and objectives: This study describes the success of an integrative behavioral–medicine inpatient treatment for complex chronic tinnitus and presents its long-term effects. In 1987 we developed and evaluated a new treatment concept of psychological treatment of complex chronic tinnitus based on international experience and results. To evaluate the influence, effects and individual results of the specific therapy we analyzed the data of 434 consecutively treated patients. To investigate the long-term effects of the treatment, we contacted the patients 15 years after discharge from the hospital. Patients and methods: We used the tinnitus questionnaire (TQ) and visual analog scales (VAS) for specific tinnitus variables (loudness, discomfort, control of tinnitus, stress, general mood). The German version of the Derogatis psychopathology checklist (SCL-90-R) was used to analyze the impact of additional symptoms (depression, anxiety, introversion, etc.). Results: Compared with a control group (patients on a waiting list) significant and clinically relevant effects were found. At the outcome, there were significant improvements in almost all parameters measured. For evaluation of the long-term effect we succeeded in contacting 312 of 434 former patients. Data were assessed using the same questionnaires that had been employed at the first contact. In all, 271 patients (86%) returned the questionnaires. Data for 244 cases (mean age 63 years; 79 females, 165 males) were complete enough to be used for data analysis. The results of the follow-up were as unexpected as clear: 15 years after conclusion of the treatment, the improvements of the tinnitus parameters and additional symptoms were stable when compared with the end of therapy.
Myelinated retinal fibers in autosomal recessive spastic ataxia of Charlevoix‐Saguenay

Background: Myelinated retinal nerve fibers are considered a hallmark of autosomal recessive spastic ataxia of Charlevoix‐Saguenay (ARSACS) in French Canadian patients. The demonstration of a worldwide distribution of this disease, as well as the almost invariable presence of a normal retina on fundoscopy in cases outside Canada, suggests that more quantitative methodologies are needed to assess the retina in ARSACS.
Nutrient dynamics and lignocellulose degradation in decomposing Quercus serrata leaf litter

The litter mass loss, concentration and mass of some major nutrient elements, degradation of lignin and cellulose in decomposing Quercus serrata Murray leaf litter were monitored for 3 years using the litterbag method. The mobility of elements during the course of the study was in the order of: K > P > C > Mg > Ca > N. Three patterns of nutrient dynamics were observed: (i) concentration increased while mass decreased (N, Mg and Ca); (ii) concentration and nutrient mass decreased (K and C); and (iii) both concentration and mass had fluctuated (P). The C to element ratio tended to increase as the element was released, and decreased as the element was retained. Nitrogen mobility in relation to carbon was characterized by three phases: (i) initial release; (ii) accumulation and (iii) final release. The decay rate (k) calculated from 0–6 months period was overestimated for an average annual rate while those of 0–36 months fit the negative single exponential model (Adj. r2 = 0.99) better than shorter periods. For lignin, the concentration had increased then decreased but tended to stabilize after 1 year while the lignin mass had continuously decreased throughout the study period. During the first 9 months, both the concentrations and mass of cellulose had fluctuated but declined thereafter. The amounts of N had initially increased but declined after 1 year; P had fluctuated while K, Ca, Mg and C had decreased throughout the study. N and C/N ratio exerted strong influence on mass loss during the first24 months but the influence of lignin emerged after 24 months.