Miracle-dz/UniFAR-FTUs huggingface dataset:
Spinal high‐mobility group box‐1 induces long‐lasting mechanical hypersensitivity through the toll‐like receptor 4 and upregulation of interleukin‐1β in activated astrocytes

Intrathecal treatment with recombinant high‐mobility group box‐1 (rHMGB1) in naïve mice leads to a persistent and significantly decreased hind paw withdrawal threshold to mechanical stimuli, suggesting that spinal HMGB1 evokes abnormal pain processing. By contrast, repeated intrathecal treatment with anti‐HMGB1 antibody significantly reverses hind paw mechano‐hypersensitivity in mice with a partial sciatic nerve ligation (PSNL). By contrast, the cellular mechanism by which spinal HMGB1 induces neuropathic pain has yet to be fully elaborated. The current study tested the hypothesis that spinal HMGB1 could induce mechanical hypersensitivity through the activation of specific receptor in glial cells. Intrathecal pretreatment with toll‐like receptor (TLR) 4 inhibitors, but not TLR5, receptor for advanced glycation end‐products and C‐X‐C chemokine receptor type 4 inhibitors, prevented rHMGB1‐evoked mechanical hypersensitivity. Activation of spinal astrocytes appears to be crucial for the mechanism of action of rHMGB1 in naïve mice, as intrathecal pretreatment with astrocytic inhibitors prevented the rHMGB1‐induced mechanical hypersensitivity. Interleukin‐1β (IL‐1β) was up‐regulated within activated astrocytes and block of TLR4 prevented the upregulation of IL‐1β. Interleukin‐1β appears to be secreted by activated astrocytes, as IL‐1β neutralizing antibody prevented rHMGB1‐induced mechanical hypersensitivity. Furthermore, intrathecal pretreatment with either MK801 or gabapentin prevented the rHMGB1‐induced mechanical hypersensitivity, suggesting roles for spinal glutamate and the N‐methyl‐d‐aspartate receptor in the mediation of rHMGB1‐induced mechanical hypersensitivity. Thus, the current findings suggest that spinal HMGB1 upregulates IL‐1β in spinal astrocytes through a TLR4‐dependent pathway and increases glutamatergic nociceptive transduction. These spinal mechanisms could be key steps that maintain neuropathic pain.
Outcomes of Double-Mobility Prosthesis in Trapeziometacarpal Joint Arthritis With a Minimal 3 Years of Follow-Up: An Advantage for Implant Stability

Background: New generation of total trapeziometacarpal joint prosthesis using double mobility concept has been used for several years. The aim of this study was to evaluate the dislocation rate with this implant after a minimal 3 years of follow-up. Methods: From September 2013 to August 2015, 200 trapeziometacarpal prostheses were implanted in 179 patients. Clinico-radiological follow-up was performed with an average of 48.2 months (36-60 months). Survival rate and dislocation rate were analyzed. Loosening of the implants and other intercurrent events were noticed. Results: Visual analog scale, Quick-DASH, strengths and range of motion improved significantly. We report a survival rate of 97% with only 0.5% of dislocation of prosthesis at 48 months of follow-up. Intercurrent events rate were similar to the ones found in literature or other studies. Conclusions: After a minimal of 3 years of follow-up, prosthesis with double mobility seemed to bring better stability in implant for thumb prosthetic replacement.
Subcutaneous emphysema in patients undergoing root canal treatment: a systematic review of the factors affecting its development and management.

BACKGROUND Subcutaneous emphysema is an infrequent mishap during root canal treatment which, in rare cases, can lead to severe complications. AIM To systematically review the literature on the factors affecting the development of subcutaneous emphysema during root canal treatment, and on its management. DATA SOURCES An electronic search was conducted in EMBASE (1947-2018), LILACS (1982-2018), PubMed (1950-2018), SciELO (1997-2018), Scopus (1970-2018), Web of Science (1900-2018), and two grey literature databases. Moreover, all issues of nine journals and four endodontic textbooks were hand-searched. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, INTERVENTIONS The retrieved studies were screened by two reviewers to select clinical studies, case reports or case series describing subcutaneous emphysema that developed during or immediately after root canal treatment in adult patients. STUDY APPRAISAL AND SYNTHESIS METHODS Included studies were critically appraised according to a custom list of quality requirements. The extracted data were arranged in tables and they were combined through a narrative synthesis. RESULTS The search retrieved 99 unique articles. Thirty six case reports and 15 case series describing 65 cases of subcutaneous emphysema in total were included in this review. The methodological quality was medium. Reported cases of emphysema more often involved females and maxillary teeth. Drying of the root canal system with air under pressure, inadvertent extrusion of hydrogen peroxide through the apical foramen, the air-water spray produced by handpieces or laser devices, and the use of ozone gas were the most commonly suspected causes. Its management involved prescription of antibiotics and NSAIDs/analgesics, local application of ice packs or compresses, and hospitalization. The signs and symptoms resolved completely within 1-17 days. LIMITATIONS Case reports and case series are a low level of evidence. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS Subcutaneous emphysema can develop during both non-surgical and surgical root canal treatment. Pressurized air streams or air-water sprays should not be directed towards the root canals or areas with mucosal discontinuity. None of the management approaches is clearly related to expedited recovery. Guidelines should be developed in order to avoid unnecessary or potentially harmful interventions. This article is protected by copyright. All rights reserved.
TANGO2 deficiency as a cause of neurodevelopmental delay with indirect effects on mitochondrial energy metabolism

Exome sequencing has recently identified mutations in the gene TANGO2 (transport and Golgi organization 2) as a cause of developmental delay associated with recurrent crises involving rhabdomyolysis, cardiac arrhythmias, and metabolic derangements. The disease is not well understood, in part as the cellular function and subcellular localization of the TANGO2 protein remain unknown. Furthermore, the clinical syndrome with its heterogeneity of symptoms, signs, and laboratory findings is still being defined. Here, we describe 11 new cases of TANGO2‐related disease, confirming and further expanding the previously described clinical phenotype. Patients were homozygous or compound heterozygous for previously described exonic deletions or new frameshift, splice site, and missense mutations. All patients showed developmental delay with ataxia, dysarthria, intellectual disability, or signs of spastic diplegia. Of importance, we identify two subjects (aged 12 and 17 years) who have never experienced any overt episode of the catabolism‐induced metabolic crises typical for the disease. Mitochondrial complex II activity was mildly reduced in patients investigated in association with crises but normal in other patients. In one deceased patient, post‐mortem autopsy revealed heterotopic neurons in the cerebral white matter, indicating a possible role for TANGO2 in neuronal migration. Furthermore, we have addressed the subcellular localization of several alternative isoforms of TANGO2, none of which were mitochondrial but instead appeared to have a primarily cytoplasmic localization. Previously described aberrations in Golgi morphology were not observed in cultured skin fibroblasts.
Reversible Cerebral Vasoconstriction Syndrome.

Autoři deklarují, že v souvislosti s předmětem studie nemají žádné komerční zájmy. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. Redakční rada potvrzuje, že rukopis práce splnil ICMJE kritéria pro publikace zasílané do biomedicínských časopisů. The Editorial Board declares that the manu script met the ICMJE “uniform requirements” for biomedical papers.
Binocular game versus part-time patching for treatment of anisometropic amblyopia in Chinese children: a randomised clinical trial

Aims To compare amblyopic-eye visual acuity (VA) and binocularity improvement of a binocular game with part-time patching in the treatment of Chinese children with anisometropic amblyopia. Methods 103 Chinese children aged 3–13 years with anisometropic amblyopia were recruited in a randomised clinical trial. Eligible participants were randomly assigned to the binocular, patching and combined groups. Primary outcome was amblyopic-eye VA improvement at 3 months. Secondary outcomes included reduction of suppression and change of stereoacuity. Results Of 85 completed participants, 44 (52%) were women and mean (SD) age was 5.99 (2.33) years. At 3 months, mean (95% CI) amblyopic-eye VA improved 0.18 (0.10–0.26), 0.28 (0.19–0.36) and 0.30 (0.21–0.39) logarithm of the minimum angle of resolution in the binocular, patching and combined groups, respectively. After adjusting for baseline VA, the difference was statistically significant (F=6.29, p=0.003), favouring as follows: the combined group, the patching group and the binocular group. After treatment, Titmus (x2 binocular=9.75, p=0.007; x2 combined=9.35, p=0.009) and dynamic stereoacuity (x2 binocular=12.56, p=0.01; x2 combined=12.66, p=0.01) improved only in the binocular and combined groups. Among groups, only Titmus improvement differed significantly (F=49.55, p<0.001). Changes of other types of stereoacuity and interocular suppression were similar. Conclusions The binocular game used in this study could improve amblyopic-eye VA and binocularity in Chinese children with anisometropic amblyopia, but it was less effective than patching in amblyopic-eye VA improvement and showed no superiority in binocularity over patching. It remains unclear whether the low treatment response of this binocular game was due to limitations of the study or its low treatment effect.
Effects of a topically applied anaesthetic on the behaviour, pain sensitivity and weight gain of dairy calves following thermocautery disbudding with a local anaesthetic

ABSTRACT Aims: To compare the effect of a topically applied anaesthetic to no pain relief or meloxicam on the behavioural responses, pain sensitivity and weight gain of calves following disbudding with or without sedation. Methods: A total of 364, 2–6 week-old calves from three commercial farms were systematically allocated to one of six treatment groups. All calves received a cornual nerve block prior to disbudding, with half restrained in a crate and half sedated with xylazine. Within these groups one third received no further treatment (control), one third were treated with meloxicam >10 minutes prior to disbudding and one third received a topical anaesthetic applied to the horn bud wounds following disbudding. The frequency of ear flicks, head shakes, head scratches and pain sensitivity of the wound were recorded on up to eight occasions over 24 hours after disbudding. Calves were weighed before, and 7 and 28 days after, disbudding to determine average daily weight gain (ADG). Results: Compared to calves in the crate-control group, all other groups had reduced ear flicks at all times following disbudding (p < 0.01). Treatment with meloxicam and topical anaesthesia in addition to sedation reduced head scratches compared to calves in the crate-control group (p ≤ 0.013). At 22 hours after disbudding head shakes were reduced in sedated calves treated with topical anaesthetic compared to calves in the crate-control group (p < 0.001). Pain sensitivity was lower in all sedated calves than unsedated calves (p < 0.001). The ADG between Days 0–7 was 0.14 (95% CI = 0.015–0.274) kg/day greater in sedated calves treated with meloxicam than calves in the crate-control group (p = 0.03), and the ADG between Days 0–28 tended to be 0.06 (95% CI=−0.01–0.13) kg/day greater in sedated calves treated with topical anaesthetic than calves in the crate-control group (p = 0.09). Conclusion and clinical relevance: Sedation of calves for disbudding reduced the pain experienced in the following 24 hours. There was a benefit to providing calves with topical anaesthetic following disbudding on behavioural responses and pain sensitivity, which was similar to that of treating calves with meloxicam.
Perspectives of key stakeholders on employment of autistic adults across the united states, australia, and sweden

Despite efforts to improve employment outcomes for autistic individuals, internationally their employment rates remain low. There is a need to better understand the factors influencing successful employment for autistic adults in the labor market from the perspectives of multiple key stakeholders. This study represents the second in a series of papers conducted as part of an International Society for Autism Research policy brief aimed at improving employment outcomes for autistic individuals. A community consultation methodology using focus groups, forums, and interviews was applied with autistic individuals (n = 19), family members (n = 18), service providers (n = 21), employers (n = 11), researchers (n = 5), and advocacy group representatives (n = 5) in Australia, Sweden, and the United States, aiming to identify the factors perceived to determine gaining and maintaining employment for autistic individuals. Directed content analysis, guided by the International Classification of Functioning, Disability and Health (ICF), was conducted to investigate the key factors influencing employment outcomes for autistic individuals. Meaningful verbal concepts, or units of text with common themes, were also derived from the qualitative data and then linked and compared to the ICF Autism Spectrum Disorder (ASD) Core‐sets. Across countries, activity and participation and environmental factor categories of the ICF were the most associated with employment outcomes. Results suggest that removal of environmental barriers and enhancing environmental facilitators may assist to remediate ASD‐related difficulties in the workplace. Autism Res 2019, © 2019 International Society for Autism Research, Wiley Periodicals, Inc.
Associated factors for progression to AIDS among HIV-infected people who use drugs: a retrospective cohort study in Dongguan, China

Objectives Injection drug use is the most important risk factor for the spread of HIV in China over the past two decades. People who use drugs (PWUD) who were diagnosed at an early stage with HIV have gradually developed AIDS. This study investigated the factors associated with disease progression following HIV diagnosis in PWUD. Design This study used a retrospective cohort study. Setting This investigation was conducted in Dongguan city, Guangdong Province, China. Participants A total of 2969 PWUD with HIV were recruited from 1 January 1995 to 31 December 2014. Primary and secondary outcome measures Kaplan-Meier method, Logistic regression and Cox proportional hazards regression model were applied to identify the related factors of progression to AIDS following HIV diagnosis. Results The study revealed that age at diagnosis, marital status, baseline CD4 T-cell counts and highly active antiretroviral therapy (HAART) were statistically significant (p<0.01), either in the patients with HIV or in patients with AIDS. Compared with HIV-infected individuals of 18 years, patients with AIDS who were at least 36 years of age possessed sharply increased HR for developing AIDS (HR=7.016, 95% CI 6.083 to 8.092, p=0.001). The single HIV-positive individuals (HR=0.691, 95% CI 0.588 to 0.811, p=0.001) were less likely to develop AIDS compared with married ones. Increasing baseline CD4 T-cell counts, HAART (HR=0.599, 95% CI 0.517 to 0.693, p=0.001) and condom usage (HR=0.825, 95% CI 0.710 to 0.959, p=0.012) were associated with delayed progression to AIDS. Conclusions Our study found that increasing baseline CD4 T-cell counts, HAART and condom usage might be associated with delayed the progression of HIV to AIDS, while increasing age at diagnosis, marital status increased hazard for developing AIDS.
Characterization of Copy Number Variations in Oral Cavity Squamous Cell Carcinoma Reveals a Novel Role for MLLT3 in Cell Invasiveness.

BACKGROUND DNA copy number variations (CNVs) are a hallmark of cancer, and the current study aimed to demonstrate the profile of the CNVs for oral cavity squamous cell carcinoma (OSCC) and elucidate the clinicopathological associations and molecular mechanisms of a potential marker derived from CNVs, mixed-lineage leukemia translocated to chromosome 3 protein (MLLT3), in OSCC carcinogenesis. MATERIALS AND METHODS CNVs in 37 OSCC tissue specimens were analyzed using a high-resolution microarray, the OncoScan array. Gene expression was analyzed by real-time polymerase chain reaction in 127 OSCC and normal tissue samples. Cell function assays included cell cycle, migration, invasion and chromatin immunoprecipitation assays. RESULTS We found a novel copy number amplified region, chromosome 9p, encompassing MLLT3 via the comparison of our data set with six other OSCC genome-wide CNV data sets. MLLT3 overexpression was associated with poorer overall survival in patients with OSCC (p = .048). MLLT3 knockdown reduced cell migration and invasion. The reduced invasion ability in MLLT3-knockdown cells was rescued with double knockdown of MLLT3 and CBP/p300-interacting transactivator with ED rich carboxy-terminal domain 4 (CITED4; 21.0% vs. 61.5%). Knockdown of MLLT3 impaired disruptor of telomeric silencing-1-like (Dot1L)-associated hypermethylation in the promoter of the tumor suppressor, CITED4 (p < .001), and hence dysregulated HIF-1α-mediated genes (TWIST, MMP1, MMP2, VIM, and CDH1) in OSCC cells. CONCLUSION We identified unique CNVs in tumors of Taiwanese patients with OSCC. Notably, MLLT3 overexpression is related to the poorer prognosis of patients with OSCC and is required for Dot1L-mediated transcriptional repression of CITED4, leading to dysregulation of HIF-1α-mediated genes. IMPLICATIONS FOR PRACTICE This article reports unique copy number variations in oral cavity squamous cell carcinoma (OSCC) tumors of Taiwanese patients. Notably, MLLT3 overexpression is related to the poorer prognosis of patients with OSCC and is required for Dot1L-mediated transcriptional repression of CITED4, leading to dysregulation of HIF-1α-mediated genes.
Partial protection from cyclical selection generates a high level of polymorphism at multiple non‐neutral sites

Temporally varying selection is known to maintain genetic polymorphism under certain restricted conditions. However, if part of a population can escape from selective pressure, a condition called the “storage effect” is produced, which greatly promotes balanced polymorphism. We investigate whether seasonally fluctuating selection can maintain polymorphism at multiple loci, if cyclically fluctuating selection is not acting on a subpopulation called a “refuge. ” A phenotype with a seasonally oscillating optimum is determined by alleles at multiple sites, across which the effects of mutations on phenotype are distributed randomly. This model resulted in long‐term polymorphism at multiple sites, during which allele frequencies oscillate heavily, greatly increasing the level of nonneutral polymorphism. The level of polymorphism at linked neutral sites was either higher or lower than expected for unlinked neutral loci. Overall, these results suggest that for a protein‐coding sequence, the nonsynonymous‐to‐synonymous ratio of polymorphism may exceed one. In addition, under randomly perturbed environmental oscillation, different sets of sites may take turns harboring long‐term polymorphism, thus making trans‐species polymorphism (which has been predicted as a classical signature of balancing selection) less likely.
Burden Among Parents of Children With Cancer in Jordan: Prevalence and Predictors

Background A diagnosis of cancer in children affects the children themselves and their entire family. Cancer treatment places parents under continuous stress and increases their life burdens. Objective The aim of this study was to assess the burden level and predictors as perceived by Jordanian parents of children with cancer. Methods A cross-sectional survey design was used to conduct the study in 2 hospitals. A sample of 264 parents of children with cancer was recruited. Data were collected using 2 instruments: the Zarit Burden Interview and the Hospital Anxiety and Depression Scale. Results The mean burden score was 38.1 (SD, 16.6), and 75.4% of parents experienced mild to severe levels of burden. Having a chronic disease, financial constraints, high levels of anxiety and depression, a child with advanced cancer, and a child experiencing pain, nausea, and vomiting predicted higher levels of burden. Conclusions Characteristics of both parents and children affect perceived levels of burden, and thus both should be taken into consideration by healthcare providers, and nurses in particular. Various interventions can be suggested to reduce the parents’ burden, including financial support, psychiatric care, and focused management of symptoms. Implications for Practice Powered by Editorial Manager and ProduXion Manager from Aries Systems Corporation, assessment of burden and screening for at-risk parents is of high importance and could be conducted briefly at admission and repeated thereafter. Healthcare institutions may need to offer various types of interventions for parents who are at high risk of burden to improve their quality of life and reduce their suffering.
Evolution of Bird Sex Chromosomes Narrated by Repetitive Sequences: Unusual W Chromosome Enlargement in Gallinula melanops (Aves: Gruiformes: Rallidae)

Among birds, species with the ZZ/ZW sex determination system generally show significant differences in morphology and size between the Z and W chromosomes (with the W usually being smaller than the Z). In the present study, we report for the first time the karyotype of the spot-flanked gallinule (Gallinula melanops) by means of classical and molecular cytogenetics. The spot-flanked gallinule has 2n = 80 (11 pairs of macrochromosomes and 29 pairs of microchromosomes) with an unusual W chromosome that is larger than the Z. Besides being totally heterochromatic, it has a secondary constriction in its long arm corresponding to the nucleolar organizer region, as confirmed by both silver staining and mapping of 18S rDNA probes. This is an unprecedented fact among birds. Additionally, 18S rDNA sites were also observed in 6 microchromosomes, while 5S rDNA was found in just 1 microchromosomal pair. Seven out of the 11 used microsatellite sequences were found to be accumulated in microchromosomes, and 6 microsatellite sequences were found in the W chromosome. In addition to the involvement of heterochromatin and repetitive DNAs in the differentiation of the large W chromosome, the results also show an alternative scenario that highlights the plasticity that shapes the evolutionary history of bird sex chromosomes.