Miracle-dz/UniFAR-FTUs huggingface dataset:
Locomotor Deficiencies and Aberrant Development of Subtype-Specific GABAergic Interneurons Caused by an Unliganded Thyroid Hormone Receptor α1

Thyroid hormone (TH) deficiency during development causes severe and permanent neuronal damage, but the primary insult at the tissue level has remained unsolved. We have defined locomotor deficiencies in mice caused by a mutant thyroid hormone receptor α1 (TRα1) with potent aporeceptor activity attributable to reduced affinity to TH. This allowed identification of distinct functions that required either maternal supply of TH during early embryonic development or sufficient innate levels of hormone during late fetal development. In both instances, continued exposure to high levels of TH after birth and throughout life was needed. The hormonal dependencies correlated with severely delayed appearance of parvalbumin-immunoreactive GABAergic interneurons and increased numbers of calretinin-immunoreactive cells in the neocortex. This resulted in reduced numbers of fast spiking interneurons and defects in cortical network activity. The identification of locomotor deficiencies caused by insufficient supply of TH during fetal/perinatal development and their correlation with subtype-specific interneurons suggest a previously unknown basis for the neuronal consequences of endemic cretinism and untreated congenital hypothyroidism, and specifies TRα1 as the receptor isoform mediating these effects.
Effects of Physical Activity on Diabetes Management and Lowering Risk for Type 2 Diabetes

Abstract Physical activity is a proven form of diabetes management and is considered a cornerstone in the prevention of diabetes. In children with diabetes, physical activity may improve insulin sensitivity and glucose uptake in skeletal muscle. Aerobic-based physical activity lasting 40-60 minutes daily for a minimum of four months is shown to enhance insulin sensitivity, and may reduce the risk for type 2 diabetes. An important adjunct to aerobic-based physical activity for diabetes prevention is resistance training. The American Academy of Pediatrics supports properly supervised strength/resistance training as a safe method for strength development in preadolescent children. Resistance training may increase skeletal muscle mass, therefore increasing whole-body glucose disposal capacity. In addition to immediate health benefits during childhood, increased physical activity in children and adolescents is likely to contribute to the establishment of healthy leisure habits over a lifetime and improved adult cardiovascular health. Large-scale intervention studies, however, are needed to determine the most effective physical activity strategies for prevention and management of type 2 diabetes in children and adolescents.
The Relationship between Religion/Spirituality and Mental Health in Patients on Maintenance Dialysis

The religious beliefs and spirituality of patients on dialysis therapy have not been studied extensively. This study aimed to investigate the relation of religion/spirituality to mental health and health representations among haemodialysis and peritoneal dialysis patients. A sample of 144 patients was recruited from three general hospitals in the broader area of Athens, consisting of 84 patients undergoing in-centre Haemodialysis (HD) and 60 patients in Continuous Ambulatory Peritoneal Dialysis (CAPD/PD). Measurements were conducted with the following instruments: the World Health Organization Quality of Life instrument (WHOQOL-BREF), the General Health Questionnaire (GHQ-28), the State-Trait Anxiety Inνentory (STAI 1/STAI 2), the Center for Epidemiologic Studies Depression Scale (CES-D) and the Multidimensional Health Locus of Control (MHLC). Religion/spirituality was associated negatively with all the subscales of GHQ-28 (somatic symptoms, anxiety/insomnia, social dysfunction, severe depression) and the GHQ-28 total score. It was also related negatively to depression, measured by CES-D scale, as well as state and trait anxiety and positively to internal health locus of control. The present study demonstrates the importance of religion/spirituality in understanding health representations of patients with Chronic Kidney Disease (CKD) and the contribution of religious beliefs to mental health.
Carriage of Streptoccoccus pneumoniae in healthy adults aged 60 years or over in a population with very high and long-lasting pneumococcal conjugate vaccine coverage in children

A serial cross-sectional study of nasopharyngeal carriage among adults aged 60 y or over was conducted in winter-spring 2012 with the aim to describe circulating Streptococcus pneumoniae in an area, Liguria Administrative Region, where the vaccine was implemented for a decade and coverage in pediatric age group reached a value close to 100% for more than 5 y, determining a picture of very high vaccine immunological pressure. The serotype-specific carriage picture in adults was compared with that observed in children by means of a cross-sectional study performed one year before using the same sampling and laboratory methods. Cluster sampling enrolled 283 adults, representative of the open population. Detection of multi-serotype carriage was performed using, real-time PCR and primer specific PCRs. Carriage prevalence of participants with at least one positive sample adjusted for age, i.e., period prevalence, was 18.7%, considering the Ligurian population as standard population, showing that the pneumococcal carriage in the elderly is not a rare event as emerged in other surveys. The long-term use of PCV7 has resulted in strong decrease of vaccine types carriage among adults and children. A multivariate analysis showed that age class and contact with children attending day care covariates were strongly associated with Streptococcus pneumoniae carriage. A strong link between the picture observed in < 5-y-old children and ≥ 60-y-old adults emerged: a strong correlation of specific-serotype prevalence between adults and children and risk factor analysis supported the role played by inter-age-group transmission.
Dynamic Engagement of Human Motion Detectors across Space–Time Coordinates

Motion detection is a fundamental property of the visual system. The gold standard for studying and understanding this function is the motion energy model. This computational tool relies on spatiotemporally selective filters that capture the change in spatial position over time afforded by moving objects. Although the filters are defined in space–time, their human counterparts have never been studied in their native spatiotemporal space but rather in the corresponding frequency domain. When this frequency description is back-projected to spatiotemporal description, not all characteristics of the underlying process are retained, leaving open the possibility that important properties of human motion detection may have remained unexplored. We derived descriptors of motion detectors in native space–time, and discovered a large unexpected dynamic structure involving a >2× change in detector amplitude over the first ∼100 ms. This property is not predicted by the energy model, generalizes across the visual field, and is robust to adaptation; however, it is silenced by surround inhibition and is contrast dependent. We account for all results by extending the motion energy model to incorporate a small network that supports feedforward spread of activation along the motion trajectory via a simple gain-control circuit.
Postnatal Loss of P/Q-Type Channels Confined to Rhombic-Lip-Derived Neurons Alters Synaptic Transmission at the Parallel Fiber to Purkinje Cell Synapse and Replicates Genomic Cacna1a Mutation Phenotype of Ataxia and Seizures in Mice

Ataxia, episodic dyskinesia, and thalamocortical seizures are associated with an inherited loss of P/Q-type voltage-gated Ca2+ channel function. P/Q-type channels are widely expressed throughout the neuraxis, obscuring identification of the critical networks underlying these complex neurological disorders. We showed recently that the conditional postnatal loss of P/Q-type channels in cerebellar Purkinje cells (PCs) in mice (purky) leads to these aberrant phenotypes, suggesting that intrinsic alteration in PC output is a sufficient pathogenic factor for disease initiation. The question arises whether P/Q-type channel deletion confined to a single upstream cerebellar synapse might induce the pathophysiological abnormality of genomically inherited P/Q-type channel disorders. PCs integrate two excitatory inputs, climbing fibers from inferior olive and parallel fibers (PFs) from granule cells (GCs) that receive mossy fiber (MF) input derived from precerebellar nuclei. In this study, we introduce a new mouse model with a selective knock-out of P/Q-type channels in rhombic-lip-derived neurons including the PF and MF pathways (quirky). We found that in quirky mice, PF-PC synaptic transmission is reduced during low-frequency stimulation. Using focal light stimulation of GCs that express optogenetic light-sensitive channels, channelrhodopsin-2, we found that modulation of PC firing via GC input is reduced in quirky mice. Phenotypic analysis revealed that quirky mice display ataxia, dyskinesia, and absence epilepsy. These results suggest that developmental alteration of patterned input confined to only one of the main afferent cerebellar excitatory synaptic pathways has a significant role in generating the neurological phenotype associated with the global genomic loss of P/Q-type channel function.
Electroencephalographic Topography Measures of Experienced Utility

Economic theory distinguishes two concepts of utility: decision utility, objectively quantifiable by choices, and experienced utility, referring to the satisfaction by an obtainment. To date, experienced utility is typically measured with subjective ratings. This study intended to quantify experienced utility by global levels of neuronal activity. Neuronal activity was measured by means of electroencephalographic (EEG) responses to gain and omission of graded monetary rewards at the level of the EEG topography in human subjects. A novel analysis approach allowed approximating psychophysiological value functions for the experienced utility of monetary rewards. In addition, we identified the time windows of the event-related potentials (ERP) and the respective intracortical sources, in which variations in neuronal activity were significantly related to the value or valence of outcomes. Results indicate that value functions of experienced utility and regret disproportionally increase with monetary value, and thus contradict the compressing value functions of decision utility. The temporal pattern of outcome evaluation suggests an initial (∼250 ms) coarse evaluation regarding the valence, concurrent with a finer-grained evaluation of the value of gained rewards, whereas the evaluation of the value of omitted rewards emerges later. We hypothesize that this temporal double dissociation is explained by reward prediction errors. Finally, a late, yet unreported, reward-sensitive ERP topography (∼500 ms) was identified. The sources of these topographical covariations are estimated in the ventromedial prefrontal cortex, the medial frontal gyrus, the anterior and posterior cingulate cortex and the hippocampus/amygdala. The results provide important new evidence regarding “how,” “when,” and “where” the brain evaluates outcomes with different hedonic impact.
Tumour necrosis factor α converting enzyme (TACE) activity in the colonic mucosa of patients with inflammatory bowel disease

Background: Anti-tumour necrosis factor α (TNF-α) antibodies are effective in Crohn's disease and perhaps ulcerative colitis but antigenicity and the high cost have raised interest in other strategies to block TNF-α. These include the TNF-α converting enzyme (TACE) which releases soluble TNF-α from transmembrane pro-TNF-α. Aim: To investigate whether TACE activity is present in human colonic mucosa. Materials and methods: Detergent extracts of cell membranes from colonic biopsies were obtained from 12 controls and 28 patients with inflammatory bowel disease. Enzyme activity was measured by hydrolysis assays using pro-TNF-α or oligopeptide substrates spanning the known pro-TNF-α cleavage site at Ala(76)-Val(77). Cleavage products were identified by western blotting, high pressure liquid chromatography, or mass spectrometry. TACE protein was localised by immunohistochemistry and identified by western blotting of detergent extracts from purified lamina propria mononuclear cells (LPMNC) or epithelial cells. Results: Detergent extracts released TNF-α from pro-TNF-α and cleaved a model oligopeptide as predicted. Substrate hydrolysis was sensitive to known TACE/matrix metalloproteinase (MMP) inhibitors, but not trocade which has low activity against TACE. The median TACE level was increased in active ulcerative colitis (147 arbitrary units (AU)/mg; p<0.01) but not in Crohn's disease (81 AU/mg) compared with controls (79 AU/mg). Both the full length proform and the active form of TACE protein were expressed in LPMNC cells and epithelial cells. Conclusions: Functional TACE activity is ubiquitously expressed in the human colon and increased in ulcerative colitis, raising interest in MMP inhibitors targeting TACE.
Serum uric acid is associated with non-dipping circadian pattern in young patients (30–40 years old) with newly diagnosed essential hypertension

Abstract Background: We aimed at evaluating the relationship between the circadian blood pressure rhythm and UA level in young patients (30–40 years old) with newly diagnosed essential hypertension. Methods: The study included 62 essential hypertensive patients and 29 healthy controls (20 men, 35 ± 3 years) divided into two groups according to 24-hour ABPM resuts: 30 dippers and 32 nondippers. Results: Nondippers showed significantly higher both serum UA levels compared to dippers and controls (6.1 ± 0.7, 5.2 ± 0.9 and 4.1 ± 0.9 mg/dL, p < 0.001, respectively); and high sensitivity C-reactive protein (hsCRP) (4.1 ± 2.2 mg/L, 3.3 ± 1.9 mg/L, and 1.4 ± 0.9 mg/L, p < 0.001, respectively). After adjusting for age, sex, body mass index, smoking, creatinine levels, hsCRP and comorbidity, multivariate logistic regression analysis revealed an independent association between serum UA levels and nondipper pattern (OR 2.44, 95%CIs 1.4–4.1, p = 0.002). Conclusion: Serum UA is independently associated with nondipper circadian pattern in young patients with newly diagnosed essential hypertension.
Aging and a Peripheral Immune Challenge Interact to Reduce Mature Brain-Derived Neurotrophic Factor and Activation of TrkB, PLCγ1, and ERK in Hippocampal Synaptoneurosomes

For reasons that are not well understood, aging significantly increases brain vulnerability to challenging life events. High-functioning older individuals often experience significant cognitive decline after an inflammatory event such as surgery, infection, or injury. We have modeled this phenomenon in rodents and have previously reported that a peripheral immune challenge (intraperitoneal injection of live Escherichia coli) selectively disrupts consolidation of hippocampus-dependent memory in aged (24-month-old), but not young (3-month-old), F344xBN rats. More recently, we have demonstrated that this infection-evoked memory deficit is mirrored by a selective deficit in long-lasting synaptic plasticity in the hippocampus. Interestingly, these deficits occur in forms of long-term memory and synaptic plasticity known to be strongly dependent on brain-derived neurotrophic factor (BDNF). Here, we begin to test the hypothesis that the combination of aging and an infection might disrupt production or processing of BDNF protein in the hippocampus, decreasing the availability of BDNF for plasticity-related processes at synaptic sites. We find that mature BDNF is markedly reduced in Western blots of hippocampal synaptoneurosomes prepared from aged animals following infection. This reduction is blocked by intra-cisterna magna administration of the anti-inflammatory cytokine IL-1Ra (interleukin 1-specific receptor antagonist). Levels of the pan-neurotrophin receptor p75NTR and the BDNF receptor TrkB (tropomyosin receptor kinase B) are not significantly altered in these synaptoneurosomes, but phosphorylation of TrkB and downstream activation of PLCγ1 (phospholipase Cγ1) and ERK (extracellular response kinase) are attenuated—observations consistent with reduced availability of mature BDNF to activate TrkB signaling. These data suggest that inflammation-evoked reductions in BDNF at synapses might contribute to inflammation-evoked disruptions in long-term memory and synaptic plasticity in aging.
Seroprevalence of antibodies against measles, rubella, mumps, varicella-zoster, and B. Pertussis in young adults of Madrid, Spain

In recent years, there has been an increase in the number of cases of certain immunopreventable diseases in our country. A high proportion of these have been recorded among the young adult population. The aim of this study was to determine the seroprevalence of antibodies against immunopreventable diseases with the greatest health impacts on the young adult population (19–39 y of age) in Madrid. We collected a total of 1,153 serum samples from healthy volunteers undergoing routine medical visits and used ELISA to determine the presence of IgG antibodies against measles, rubella, mumps, and varicella zoster, as well as Bordetella pertussis. The Pearson’s χ2 test was used to compare prevalences, the Mann-Whitney U test was used to compare means, and the Kruskal-Wallis test was applied for variables with more than 2 categories. Statistical significance was achieved with p values of < 0.05. The global prevalence of antibodies was 92.1% for measles, 94.4% for rubella, 88.3% for mumps, 92.8% for varicella zoster, and 70.2% for B. pertussis. No statistically significant differences were found between genders. The prevalence of antibodies against measles was more than 95% in the group of individuals born after 1986, and the percentage of individuals susceptible to rubella was less than 5% in women born after 1986. In spite of adequate vaccination coverage, in our region, a population of young adults exists who have not achieved the objectives of the WHO for the elimination of measles and congenital rubella syndrome.
Passive immunization for the public health control of communicable diseases: Current status in four high-income countries and where to next

The practice of passive immunization with human immune globulin (IG) for the control of communicable diseases (measles, rubella and hepatitis A) differs somewhat between Australia, the United States of America, the United Kingdom, and New Zealand despite the many similarities of these countries, including disease incidence rates and population immunity. No minimum effective dose of IG has been identified for protecting susceptible contacts of measles or hepatitis A. Recommended passive immunization practice for susceptible pregnant contacts of rubella is based on limited evidence in all countries. We suggest that gaps in the evidence base need to be addressed to appropriately inform the role of passive immunization in public health practice into the future.
Temporal Sequence of Attentional Modulation in the Lateral Intraparietal Area and Middle Temporal Area during Rapid Covert Shifts of Attention

In the visual system, spatial attention enhances sensory responses to stimuli at attended locations relative to unattended locations. Which brain structures direct the locus of attention, and how is attentional modulation delivered to structures in the visual system? We trained monkeys on an attention-switch task designed to precisely measure the onset of attentional modulation during rapid shifts of spatial attention. Here we show that attentional modulation appears substantially earlier in the lateral intraparietal area (LIP) than in an anatomically connected lower visual area, the middle temporal area. This temporal sequence of attentional latencies demonstrates that endogenous changes of state can occur in higher visual areas before lower visual areas and satisfies a critical prediction of the hypothesis that LIP is a source of top-down attentional signals to early visual cortex.
Effectiveness of one dose of mumps vaccine against clinically diagnosed mumps in Guangzhou, China, 2006–2012

Although mumps-containing vaccines were introduced in China in 1990s, mumps continues to be a public health concern due to the lack of decline in reported mumps cases. To assess the mumps vaccine effectiveness (VE) in Guangzhou, China, we performed a 1:1 matched case-control study. Among children in Guangzhou aged 8 mo to 12 y during 2006 to 2012, we matched one healthy child to each child with clinically diagnosed mumps. Cases with clinically diagnosed mumps were identified from surveillance sites system and healthy controls were randomly sampled from the Children’s Expanded Programmed Immunization Administrative Computerized System in Guangzhou. Conditional logistic regression was used to calculate VE. We analyzed the vaccination information for 1983 mumps case subjects and 1983 matched controls and found that the overall VE for 1 dose of mumps vaccine, irrespective of the manufacture, was 53.6% (95% confidence interval [CI], 41.0–63.5%) to children aged 8 mo to 12 y. This post-marketing mumps VE study found that immunization with one dose of the mumps vaccine confers partial protection against mumps disease. Evaluation of the VE for the current mumps vaccines, introduction of a second dose of mumps vaccine, and assessment of modifications to childhood immunization schedules is essential.
A Synthetic Reinforcement Patch in Repair of Challenging Two-Tendon Rotator Cuff Tears

Background The repair of chronic massive tendon tears may be a challenging procedure, especially with a frayed tendon caused by degeneration. The aim of this case series was to evaluate the outcome of a synthetic patch in the repair of complex rotator cuff tears, with regard to shoulder function, pain relief and quality of life. Methods A synthetic patch (Artelon® Tissue Reinforcement; Artimplant AB, Västra Frölunda, Sweden) was used in 17 patients with challenging repairs of chronic rotator cuff tears. The outcome of surgical treatment was evaluated after 3, 6 and 12 months by the Constant functional score and the Western Ontario Rotator Cuff (WORC) score. Results Significantly less pain and improved shoulder function, as evaluated by the Constant score, was seen 1 year after surgery, as well as an increased WORC score as a measure of improved disease-related quality of life. Re-operation was performed in one patient as a result of a re-tear. There were no complications related to the use of the reinforcement patch. Conclusions This case series showed satisfying results in technically challenging repairs of rotator cuff tears with the use of a synthetic reinforcement patch. Postoperatively, the patients showed less pain and improved shoulder function to the extent to perform better in daily life activities.