Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional analysis of novel genetic variation in the thyroid hormone activating type 2 deiodinase.

CONTEXT Thyroid hormones (TH) are important for normal brain development and abnormal TH regulation in the brain results in neurocognitive impairments. The type 2 deiodinase (D2) is important for local TH control in the brain by generating the active hormone T3 from its precursor T4. Dysfunction of D2 likely results in a neurocognitive phenotype. No mutations in D2 have been reported yet. OBJECTIVE The objective of the study was to identify D2 mutations in patients with intellectual disability and to test their functional consequences. DESIGN, SETTING, AND PATIENTS The patients were selected from the multicenter Thyroid Origin of Psychomotor Retardation study, which is a cohort of 946 subjects with unexplained intellectual disability. Based on characteristic serum TH values, the coding region of the DIO2 gene was sequenced in 387 patients. Functional consequences were assessed by in vitro D2 assays or intact cell metabolism studies using cells transfected with wild-type or mutant D2. RESULTS Sequence analysis revealed two heterozygous mutations: c.11T>A (p.L4H) in three subjects and c.305C>T (p.T102I) in one subject. Sequence analysis of family members revealed several carriers, but no segregation was observed with thyroid parameters or neurocognitive phenotype. Extensive tests with different in vitro D2 assays did not show differences between wild-type and mutant D2. CONCLUSION This study describes the identification and functional consequences of novel genetic variation in TH activating enzyme D2. Family studies and functional tests suggest that these variants do not underlie the neurocognitive impairment. Altogether our data provide evidence of the existence of rare but apparently harmless genetic variants of D2.
Metabolomic profile associated with insulin resistance and conversion to diabetes in the Insulin Resistance Atherosclerosis Study.

CONTEXT Metabolomic profiling of amino acids and acylcarnitines has revealed consistent patterns associated with metabolic disease. OBJECTIVE This study used metabolomic profiling to identify analytes associated with insulin sensitivity (SI) and conversion to type 2 diabetes (T2D). DESIGN A multiethnic cohort from the Insulin Resistance Atherosclerosis Study. SETTING Community-based. PATIENTS A total of 196 subjects (European American, Hispanic, and African American) were selected to represent extremes of the SI distribution and conversion to T2D between baseline and followup exams. MAIN OUTCOME Mass spectrometry-based profiling of 69 metabolites. Subjects participated in a frequently sampled i.v. glucose tolerance test to measure SI and acute insulin response. T2D status was determined by a 2-hour oral glucose tolerance test. RESULTS Logistic regression analysis from 72 high and 75 low SI subjects revealed significantly decreased glycine and increased valine, leucine, phenylalanine, and combined glutamine and glutamate (P = .0079-7.7 × 10(-6)) in insulin-resistant subjects. Ethnic-stratified results were strongest in European Americans. Comparing amino acid profiles between subjects that converted to T2D (76 converters; 70 nonconverters) yielded a similar pattern of associations: decreased glycine and increased valine, leucine, and combined glutamine and glutamate (P = .016-.00010). Importantly, β-cell function as a covariate revealed a similar pattern of association. CONCLUSIONS A distinct pattern of differences in amino acids were observed when comparing subjects with high and low levels of SI. This pattern was associated with conversion to T2D, remaining significant when accounting for β-cell function, emphasizing a link between this metabolic profile and insulin resistance. These results demonstrate a consistent metabolic signature associated with insulin resistance and conversion to T2D, providing potential insight into underlying mechanisms of disease pathogenesis.
Volume de iogurte light e sensações subjetivas do apetite de homens eutróficos e com excesso de peso

OBJECTIVE: This study aimed to evaluate the effect of light yogurt volume on the food intake of healthy men regardless of other variables. METHODS: Air was added to the yogurt by mixing it with a commercially available product, Emustab®, (6g/300ml) and homogenized in a semi-industrial blender. Three volumes of yogurt were used: 300, 450 and 600ml. Twenty healthy volunteers participated in the study, 10 with normal weight, Body Mass Index from 19 to 24.9kg/m2 and 10 with excess weight, Body Mass Index >25kg/m2. Each one of them was given a yogurt volume in three different days in the morning, after a 12 hour fast. After the intake of each yogurt volume, a visual analog scale was used to assess the subjective sensations of satiety, hunger and desire for specific foods. RESULTS: Light yogurt volumes affected the satiety of both studied groups and the greater volume was more effective (p<0.01). The highest hunger score was obtained after the 300ml intake, followed by 450 and 600ml (p<0.01). The desire for sweet, salty and fatty foods and snacks was not influenced by time and yogurt volume in either studied group. Energy intake between the days which yogurt was consumed and yogurt was not consumed was not statistically different (p<0.05). CONCLUSION: The results of this study suggest that the volume of light yogurt, regardless of other factors, may influence appetite and satiety.
Le Sequenze Turbo Spin Echo

Le sequenze spin echo sono fino al giorno d'oggi le più utilizzate nella tomografia con Risonanza Magnetica. Il loro principale vantaggio è l'alta sensibilita alle patologie delle immagine pesate in T2. Recentemente sono state introdotte nuove sequenze, denominate Fast Spin Echo o Turbo Spin Echo, a seconda dell'industria che le produce, le quali grazie ad un diverso modo di acquisire i dati permettono di ridurre i tempi di esame, mantenendo un contrasto simile alle immagini ottenute con le spin echo convenzionali. Lo schema di acquisizione diverso comporta delle piccole differenze con le immagini a cui sono abituati i neuroradiologi: segnale iperintenso del grasso anche nelle immagini pesate in T2; minore sensibilita agli artefatti da suscettibilità; presenza di altri artefatti, quali quello da troncamento o l'effetto bordo, visibili soprattutto se non si scelgono opportunamente i parametri. Tali sequenze si sono rivelate molto interessanti non solo per il risparmio di tempo, ma anche per gli studi in alta risoluzione o per applicazioni cliniche particolari.
Lingonberry Anthocyanins Protect Cardiac Cells from Oxidative Stress‐Induced Apoptosis

Lingonberry grown in Canada contains exceptionally high levels of anthocyanins, the pigments that give the berries their red color, as well as other polyphenols, including resveratrol, quercetin, and proanthocyanidins, which may have antioxidant properties. Anthocyanin‐rich diets have been shown to be associated with decreased cardiovascular disease and overall mortality. Oxidative stress plays an important role in cardiovascular disease by impairing function and triggering apoptosis of cardiomyocytes. In this study, we investigated whether physiologically relevant doses of pure anthocyanins and lingonberry extracts could protect H9c2 cardiomyoblasts from oxidative stress‐induced cell death. Anthocyanins were added at 10 ng mL−1 (20 nmol L−1) to cell culture media prior to induction of oxidative stress with 600 μM hydrogen peroxide. After 2 hours of hydrogen peroxide treatment, apoptosis and necrosis were detected in H9c2 cells via flow cytometry using FLICA 660 caspase 3/7 combined with YO‐PRO‐1 to allow differentiation between viable, early apoptotic, late apoptotic, and necrotic cells. Apoptosis was confirmed using Hoechst 33258 and fluorescence microscopy. Each of the three major anthocyanins found in lingonberry, cyanidin‐3‐galactoside, cyandin‐3‐glucoside, and cyanidin‐3‐arabinoside, was protective against hydrogen peroxide‐induced apoptosis in H9c2 cells at 10 ng mL−1 and preserved the number of viable cells to match the non‐hydrogen peroxide‐treated group. A combination of the three anthocyanins tested at 10 ng mL−1 was also protective. A lingonberry extract tested at three concentrations produced a dose‐dependent protective effect. This study demonstrates that lingonberry anthocyanins could protect cardiac cells from oxidative stress‐induced apoptosis and may have cardioprotective effects.
Effects of sea ice cover on the swarming behaviour of Antarctic krill, Euphausia superba

Much of the distribution range of Antarctic krill, Euphausia superba, is covered by permanent or seasonal sea ice. Sea ice extent has been implicated as a major factor affecting reproductive success of krill and krill dispersal, but little is known of the way in which ice cover may influence krill behaviour. This is largely because the under-ice environment is difficult to study. Ship-borne echosounders have, however, detected krill aggregations in midwater in ice-covered regions. We used 120-kHz echograms collected underway during three cruises that crossed ice-covered and adjacent open waters in the Bellingshausen, Weddell, and Scotia seas to compare morphological and next-neighbour characteristics of krill swarms within and without ice cover. No significant differences were detected between the horizontal and vertical extent of swarms or swarm next-neighbour distance in ice-covered or open waters. Distributions of swarm mid-depths did, however, differ significantly between ice-covered and open areas in.
Neurobehavioral deficits, diseases, and associated costs of exposure to endocrine-disrupting chemicals in the European Union.

CONTEXT Epidemiological studies and animal models demonstrate that endocrine-disrupting chemicals (EDCs) contribute to cognitive deficits and neurodevelopmental disabilities. OBJECTIVE The objective was to estimate neurodevelopmental disability and associated costs that can be reasonably attributed to EDC exposure in the European Union. DESIGN An expert panel applied a weight-of-evidence characterization adapted from the Intergovernmental Panel on Climate Change. Exposure-response relationships and reference levels were evaluated for relevant EDCs, and biomarker data were organized from peer-reviewed studies to represent European exposure and approximate burden of disease. Cost estimation as of 2010 utilized lifetime economic productivity estimates, lifetime cost estimates for autism spectrum disorder, and annual costs for attention-deficit hyperactivity disorder. Setting, Patients and Participants, and Intervention: Cost estimation was carried out from a societal perspective, ie, including direct costs (eg, treatment costs) and indirect costs such as productivity loss. RESULTS The panel identified a 70-100% probability that polybrominated diphenyl ether and organophosphate exposures contribute to IQ loss in the European population. Polybrominated diphenyl ether exposures were associated with 873,000 (sensitivity analysis, 148,000 to 2.02 million) lost IQ points and 3290 (sensitivity analysis, 3290 to 8080) cases of intellectual disability, at costs of €9.59 billion (sensitivity analysis, €1.58 billion to €22.4 billion). Organophosphate exposures were associated with 13.0 million (sensitivity analysis, 4.24 million to 17.1 million) lost IQ points and 59 300 (sensitivity analysis, 16,500 to 84,400) cases of intellectual disability, at costs of €146 billion (sensitivity analysis, €46.8 billion to €194 billion). Autism spectrum disorder causation by multiple EDCs was assigned a 20-39% probability, with 316 (sensitivity analysis, 126-631) attributable cases at a cost of €199 million (sensitivity analysis, €79.7 million to €399 million). Attention-deficit hyperactivity disorder causation by multiple EDCs was assigned a 20-69% probability, with 19 300 to 31 200 attributable cases at a cost of €1.21 billion to €2.86 billion. CONCLUSIONS EDC exposures in Europe contribute substantially to neurobehavioral deficits and disease, with a high probability of >€150 billion costs/year. These results emphasize the advantages of controlling EDC exposure.
Rehabilitation training for home-based palliative care community health workers: a pilot study

Abstract Introduction Community health workers are an essential part of the delivery of palliative care in the resource-limited country of Malawi. The purpose of this pilot study was to evaluate a training programme in rehabilitation for home-based palliative community health workers. Methods The programme was a 3-day training in rehabilitation for palliative care for 20 community health workers at St Gabriel's, a rural referral hospital in Malawi. A pre- and post- knowledge test, a skills competency check, ongoing formative assessment, observations of skills in the home visit, and reporting of skills used in the village were used to evaluate the training programme. Results Participants (n = 20) showed significantly greater knowledge on the post-test (M = 7.35, SE = 0.406) than on the pre-test (M = 4.25, SE = 0.422, t (19) =−7.566, P = 0.000). Competency in all 22 physical therapy skills was demonstrated by 100% of the participants (n = 20). During the formative assessment and observations during the 3-day programme, participants were able to use all of the 22 physical therapy skills. At 2-week post-training, the participants surveyed (n = 14) reported using 21 of 22 physical therapy skills and teaching all 21 of the skills used to the caregiver of the patient. Discussion This study demonstrated the knowledge and skills learned in a training programme with lecture, practice sessions and application components in a resource-limited setting. The training programme provides a basis for future training and curriculum development for palliative care community health workers.
Effect of Short-term Intensive Insulin Therapy on Post-challenge Hyperglucagonemia in Early Type 2 Diabetes.

CONTEXT Hyperglucagonemia is a characteristic feature of type 2 diabetes (T2DM) that has been postulated to be due to β-cell dysfunction and the resultant loss of insulin-mediated α-cell suppression. When administered in early T2DM, short-term intensive insulin therapy (IIT) can improve β-cell function, resulting in reduced glycemic variability. OBJECTIVE To evaluate the impact of IIT on hyperglucagonemia and its associations with β-cell function and glycemic variability. Design/Setting/Participants/Intervention: Sixty-two patients with T2DM of mean 3.0 ± 2.1 years duration and glycated hemoglobin of 6.8 ± 0.7% underwent 4 weeks of IIT, consisting of basal detemir and premeal insulin aspart. MAIN OUTCOME MEASURES Glucagon response was measured by area under the glucagon curve (AUCglucagon) on oral glucose tolerance test at baseline and 1 day post-IIT. β-Cell function before and after IIT was assessed by Insulin Secretion-Sensitivity Index-2 and ΔISR0-120/Δglucose0-120*Matsuda index (where ISR is the prehepatic insulin secretion rate determined by C-peptide deconvolution). Glucose variability was assessed in both the first and last weeks by the coefficient of variation of capillary glucose on daily six-point self-monitoring profiles. RESULTS Both Insulin Secretion-Sensitivity Index-2 and ΔISR0-120/Δglucose0-120*Matsuda index demonstrated improvement in β-cell function after IIT (both P ≤ .02), accompanied by reduced glycemic variability (P = .05). There was a marked reduction in AUCglucagon after IIT, as compared to baseline (P < .001). However, the decrease in AUCglucagon was not associated with the change in either β-cell measure (both P ≥ .34) or glucose variability (P = .37). CONCLUSIONS Short-term IIT can reduce post-challenge hyperglucagonemia in early T2DM, but this effect does not appear to be due to improved β-cell function.
Reversible Albumin-Binding GH Possesses a Potential Once-Weekly Treatment Profile in Adult Growth Hormone Deficiency.

CONTEXT NNC0195-0092 is a reversible, albumin-binding GH derivative, developed for once-weekly administration. OBJECTIVES The objective of the study was to evaluate safety, local tolerability, pharmacodynamics, and pharmacokinetics of multiple, once-weekly doses of NNC0195-0092, compared with daily GH. DESIGN AND SETTING This was a phase 1, randomized, open-label, active-controlled, multiple-dose, dose-escalation trial. PATIENTS Thirty-four GH-treated adult subjects (male, n = 25) with GH deficiency participated in the study. INTERVENTIONS AND MAIN OUTCOME MEASURES Subjects were sequentially assigned into four cohorts of eight subjects, randomized within each cohort (3:1) to once-weekly NNC0195-0092 (n = 6) for 4 weeks (0.02, 0.04, 0.08, and 0.12 mg/kg) or daily injections of Norditropin NordiFlex (n = 2) for 4 weeks with a dose replicating the pretrial dose of somatropin. A safety assessment was performed prior to initiating treatment at the next dose level of NNC0195-0092. Daily GH treatment was discontinued 14 days before the trial start. Blood samples were drawn for assessment of safety, pharmacokinetics, pharmacodynamics (IGF-1 and IGF-binding protein-3) profiles, and immunogenicity studies. RESULTS Numbers of adverse events were similar at the dose levels of 0.02, 0.04, and 0.08 mg/kg NNC0195-0092 vs daily injections of Norditropin NordiFlex, whereas the number of adverse events was greater at the highest dose level of NNC0195-0092 (0.12 mg/kg). NNC0195-0092 (area under the curve[0-168h]) and peak plasma concentration) increased in a dose-dependent manner, and a dose-dependent increase in IGF-1 levels was observed. IGF-1 profiles were elevated for at least 1 week, and for the 0.02-mg/kg and 0.04-mg/kg NNC0195-0092 doses, the observed IGF-1 levels were similar to the levels for the active control group. CONCLUSION Four once-weekly doses of NNC0195-0092 (dose range 0.02-0.12 mg/kg) administered to adult patients with GH deficiency were well tolerated, and IGF-1 profiles were consistent with a once-weekly treatment profile. No clinically significant safety and tolerability signals causally related to NNC0195-0092 were identified, nor were any immunogenicity concerns revealed.
Menopausal Hormone Therapy and Mortality: A Systematic Review and Meta-Analysis.

OBJECTIVES The objective was to assess the effect of menopausal hormonal therapy (MHT) on all-cause and cause-specific mortality. METHODS We conducted a comprehensive search of several databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, and Scopus) from inception until August 2013. We included randomized controlled trials (RCTs) of more than 6 months of duration comparing MHT with no treatment. Pairs of independent reviewers selected trials, assessed risk of bias and extracted data. We estimated risk ratios (RRs) and 95% confidence intervals (CIs) using the random-effects model. RESULTS We included 43 RCTs at moderate risk of bias. Meta-analysis showed no effect on mortality (RR 0.99 [95% CI, 0.94-1.05]), regardless of MHT type or history of preexisting heart disease. No association was found between MHT and cardiac death (RR 1.04 [95% CI 0.87-1.23]) or stroke (RR 1.49 [95% CI 0.95-2.31]). Estrogen plus progesterone use was associated with a likely increase in breast cancer mortality (RR 1.96 [95% CI 0.98-3.94]), whereas estrogen use was not. MHT use was not associated with mortality of other types of cancer. In 5 trials, MHT was likely started at a younger age: 2 RCTs with mean age less than 60 and 3 RCTs with MHT started less than 10 years after menopause. Meta-analysis of these 5 RCTs showed a reduction of mortality with MHT (RR 0.70 [95% CI 0.52-0.95]). CONCLUSION The current evidence suggests that MHT does not affect the risk of death from all causes, cardiac death and death from stroke or cancer. These data may be used to support clinical and policy deliberations about the role of MHT in the care of symptomatic postmenopausal women.
The Impact of Hypoparathyroidism Treatment on the Kidney in Children: Long-Term Retrospective Follow-Up Study.

CONTEXT Adults with hypoparathyroidism have significant rates of nephrocalcinosis and impaired renal function. Little is known about the impact of hypoparathyroidism treatment on renal function in children. OBJECTIVES To determine the prevalence and predictors for renal abnormalities (nephrocalcinosis and decreased estimated glomerular filtration rate [eGFR]) in children with treated hypoparathyroidism. DESIGN AND SETTING A retrospective chart review of patients with permanent hypoparathyroidism at the Hospital for Sick Children, Toronto, between 1996 and 2013. PATIENTS Data of 29 patients (15 males) followed for at least 1 year with documented hypoparathyroidism were analyzed. Mean duration of follow up was 7.4 ± 5 years. MAIN OUTCOME MEASURES The presence or absence of nephrocalcinosis as detected on ultrasound and eGFR were evaluated. RESULTS Time-weighted average serum measurements were calculated for all biochemical variables. Mean total and ionized serum calcium were 8.9 ± 0.8 and 4.6 ± 0.5 mg/dL, respectively. Nephrocalcinosis was observed in 38% of the subjects, with the most significant predictors being the degree of relative hypercalcemia and hyperphosphatemia (R(2) = 0.47, P < . 01). Although all patients had an eGFR greater than 60, in 45% of the children, the eGRF was between 60 and 90 mL/min per 1.73 m(2). Higher calcium concentrations (r = -0.42, P = .02) and a greater proportion of time with relative hypercalcemia (r = -0.41, P = .03) were associated with lower eGFR. CONCLUSIONS Our results establish that children with hypoparathyroidism treated with calcitriol and calcium supplements are at risk for nephrocalcinosis and decreased eGFR. Because hypoparathyroidism is most commonly a life-long condition, careful monitoring and management of calcium abnormalities has important future implications.
Engineering bacterial two-component system PmrA/PmrB to sense lanthanide ions.

The Salmonella PmrA/PmrB two-component system uses an iron(III)-binding motif on the cell surface to sense the environmental or host ferric level and regulate PmrA-controlled gene expression. We replaced the iron(III)-binding motif with a lanthanide-binding peptide sequence that is known to selectively recognize trivalent lanthanide ions. The newly engineered two-component system (PmrA/PmrB) can effectively sense lanthanide ion and regulate gene expression in E. coli . This work not only provides the first known lanthanide-based sensing and response in live cells but also demonstrates that the PmrA/PmrB system is a suitable template for future synthetic biology efforts to construct bacteria that can sense and respond to other metal ions in remediation or sequestration.