Miracle-dz/UniFAR-FTUs huggingface dataset:
Nonunion and Reoperation Following Proximal Interphalangeal Joint Arthrodesis and Associated Patient Factors

Background Proximal interphalangeal joint (PIPJ) arthrodesis can provide reliable pain relief and restore hand function in patients with PIPJ arthritis. However, there is a paucity of literature on patient-specific preoperative risk factors that are associated with adverse outcomes after PIPJ arthrodeses. Therefore, the primary purpose of this study was to assess preoperative predictors of nonunion and reoperation after PIPJ arthrodesis. Methods This study identified all patients who underwent PIPJ arthrodesis at a single community practice between 1987 and 2013. The final analysis included 415 PIPJs treated with arthrodesis. The mean follow-up was 1.3 years. Data on preoperative diagnosis, demographics, comorbidities, and operative techniques were recorded, as well as the occurrence of nonunions and reoperations. Logistic regression models were used to identify independent risk factors of nonunion and reoperation. Results There were 40 nonunions (10%) and 62 reoperations (15%). Of the reoperations, there were 39 incidences of isolated hardware removal, 9 irrigation and debridement, 8 amputations, 5 revision arthrodeses, and 1 corrective osteotomy. The highest number of nonunions occurred in the traumatic diagnosis group (37%), followed by the rheumatoid group (23%) and the scleroderma group (15%). The highest number of reoperations occurred within the traumatic joint disorder group (40%), followed by the rheumatoid group (24%) and the scleroderma group (11%). Multivariate analysis revealed that male sex (P < .01) and hepatic disease (P = .03) were significant risk factors of nonunion. Male sex was also significantly associated with increased reoperation risk (P < .01). Conclusion Risks of nonunions and reoperations after PIPJ arthrodeses are low; however, these findings may guide clinicians and patients in the preoperative decision-making process and help with targeted postoperative surveillance to mitigate these risks.
NEW FOSSIL EPHEMEROPTERA AND COLEOPTERA FROM THE LADINIAN(MIDDLE TRIASSIC) OF CANTON TICINO (SWITZERLAND)

Two insects are described from the sediments of the uppermost Ladinian (Middle Triassic) of Meride (Canton Ticino, Switzerland). Tintorina triassica gen. n. sp. n. , a representative of a new family, Tintoriniidae, of the Ephemeroptera, is described on the basis of two specimens, one being almost complete; a single elytron is ascribed to Notocupes sp. ind. (Cupedidae, Coleoptera). The ephemeroptera specimens possibly belong to a previously unrecognized Triassic suborder/order within the infraorder Ephemeroidea. Apart from the taxonomic interest of this find, it is pointed out that these are the first fossil insects found in the classic deposits of Monte San Giorgio-Besano, famous mostly for its vertebrates. The presence of Ephemeroptera confirms the existence of land with adjacent fresh-water basins where the preservation of many organisms in fine-grained matrix was possible.
Molecular pathogenesis of spinal bulbar muscular atrophy (Kennedy's disease) and avenues for treatment

Purpose of review The aim of this study was to illustrate the current understanding and avenues for developing treatment in spinal and bulbar muscular atrophy (SBMA), an inherited neuromuscular disorder caused by a CAG trinucleotide repeat expansion in the androgen receptor (AR) gene. Recent findings Important advances have been made in characterizing the molecular mechanism of the disease, including the disruption of protein homeostasis, intracellular trafficking and signalling pathways. Biomarkers such as MRI quantification of muscle volume and fat fraction have been used to track disease progression, and will be useful in future clinical studies. Therapies tested and under development have been based on diverse strategies, including targeting mutant AR gene expression, stability and activity, and pathways that mitigate disease toxicity. Summary We provide an overview of the recent advances in understanding the SBMA disease mechanism and highlight efforts to translate these insights into well tolerated and effective therapy.
Acceleration of Extracellular Electron Transfer by Alternative Redox-Active Molecules to Riboflavin for Outer-Membrane Cytochrome c of Shewanella oneidensis MR-1

Extracellular electron transfer (EET) between outer membrane c-type cytochromes (OM c-Cyts) of Shewanella oneidensis MR-1 and anodic and cathodic electrodes is markedly enhanced by the presence of riboflavin that operates as a redox active center in OM c-Cyt protein OmcA. Here, to obtain insight into the EET mechanism via bound riboflavin in OmcA, we replaced riboflavin with two flavin-like polycyclic molecules, safranin (Saf) and anthraquinone-1-sulfonate (α-AQS), and examined the influence of the interaction with OmcA and the potential of these redox molecules for the rate of cathodic EET by MR-1 in vivo. The results of electrochemical assays with wild-type and mutant strains of MR-1 lacking OmcA showed that both Saf and α-AQS increased the cathodic current production for fumarate reduction at −0.45 V versus SHE as a bound cofactor in OmcA. Dissociation constant and enhancement factor analyses of Saf and α-AQS suggested that the N(5) atom in the isoalloxazine ring of riboflavin is important for the affi.
A randomized trial of a brief behavioral health lifestyle program for outpatient cardiology clinics

Research on lifestyle programs for patients with coronary artery disease (CAD) has largely recruited from hospitals and/or recruited following acute coronary syndrome. By contrast, this study evaluated a 3-session behavioral health program for patients with stable CAD treated in an outpatient cardiology clinic. Thirty-three patients were randomized to the behavioral lifestyle intervention or to Treatment as Usual (TAU). A priori feasibility and acceptability criteria were met, and reliable change analyses revealed that at post-treatment and 30-day follow-up, significantly more intervention participants than TAU participants exhibited increased self-efficacy compared with baseline.
The effect of intermittent hypoxia training on migraine: a randomized controlled trial.

OBJECTIVE To study the effect of intermittent hypoxia training (IHT) for migraine. DESIGN A single-blind, randomized controlled trial. All participants were recruited from a rehabilitation department in an acute university-affiliated hospital. METHODS Participants with migraines were randomly assigned to two groups (IHT group and control group). The Migraine Disability Assessment (MIDAS), Visual Analog Scale (VAS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Vascular endothelial growth factor (VEGF), calcitonin gene related peptide (CGRP) and cerebrovascular hemodynamic parameters were collected at baseline and end of the 8th week. The attack frequencies of migraines were evaluated at 3 months. RESULTS Among the 48 subjects, five males and forty-three females, the ages ranged from 19 to 53 years old (mean ± SD = 31.3±7.78). MIDAS, SF-36, VAS, BAI, BDI, VEGF, CGRP and cerebrovascular hemodynamic parameters were improved after IHT intervention. There were significant differences between IHT group and the control group in MIDAS, SF-36, VAS, BAI, BDI, VEGF, CGRP and cerebrovascular hemodynamic parameters at the end of the 8th weeks (P<0.05). Attack frequencies were improved within 3 months after IH training intervention (P<0.01), but not in the control group (P>0.05). No adverse events occurred during the study. CONCLUSION IHT could improve migraines after intervention up to three months. IHT could be an effective method for relieving a migraine.
The problem of vaccination refusal: a review with guidance for pediatricians

Purpose of review In the wake of multiple recent outbreaks of the measles and other vaccine-preventable diseases, it is crucial to understand and address parental concerns about vaccination. The purposes of this review are: to identify the causes of vaccine resistance, to elucidate the variables that have led to the success or failure of interventions to date, and to consider implications for pediatricians treating children whose parents are vaccination-resistant. Recent findings Recent research draws on insights from cognitive science to understand vaccine resistance and to develop more effective interventions. Studies show that vaccine resistors are more likely to value lifestyle liberty, to favor individualistic over hierarchical worldviews, and to believe in conspiracy theories. Interventions that seek primarily to correct erroneous beliefs about the dangers of vaccination are likely to fail or even backfire. On the other hand, intervention strategies, such as motivational interviewing, in which the provider elicits and shows respect for parents’ values and concerns while empowering them to make well informed and well reasoned decisions, are more likely to be successful. Parents cite a trusting relationship with their pediatrician as the most important factor influencing their decision to vaccinate. Summary Pediatricians are in the best position to successfully apply insights from cognitive science and intervention research to overcome vaccination-hesitancy.
Prognostic value of the TGFβ1 rs4803455 single nucleotide polymorphism in small cell lung cancer

Background: Small cell lung cancer (SCLC) is one of the greatest therapeutic challenges of oncology. Potential associations between single nucleotide polymorphisms in heat shock protein β1 (HSPB1) and transforming growth factor β1 (TGFβ1) and survival have been investigated. Methods: A prospective multicenter study of 94 patients with SCLC treated between 2013 and 2016 was conducted. Clinical, tumour-related, therapeutic, and genetic (9 SNPs of TGFβ1 gene and 5 of HSPB1 gene) variables were analyzed. Results: The cohort included 77 men and 17 women with a median age of 61 years. Eighty percent presented with limited stage at diagnosis and received thoracic radiation with a median dose of 45 Gy (twice-daily radiation in 42%). Forty-seven percent received concurrent platinum-based chemotherapy and 57% received prophylactic cranial irradiation (PCI). Overall survival (OS) was 34% at 2 years and 16% at 3 years. In multivariate analysis, the rs4803455:CA genotype of the TGFβ1 gene showed a statistically significant association with lower disease-free survival (DFS; hazard ratio [HR] 3.13; confidence interval [CI] 1.19–8.17; p = 0.020) and higher local recurrence (HR 3.80; CI 1.37–10.5; p = 0.048), and a marginal association with lower OS (HR 1.94; CI 0.98–3.83; p = 0.057). A combined analysis showed that patients receiving PCI and carrying the rs4803455:CA genotype had statistically significant lower OS (p < 0.001) and DFS (p < 0.001) than patients receiving PCI and carrying the rs4803455:AA genotype. Conclusions: Genetic analysis showed the CA genotype of TGFβ1 SNP rs4803455 was associated with worse prognosis in patients with SCLC and could be considered as a potential biomarker.
Inflammatory risk factors for hypertriglyceridemia in patients with severe influenza

Objective Inflammation and viral infections can induce significant changes in lipid metabolism. Hypertriglyceridemia (HTG) often occurs secondary to obesity, which is an independent risk factor for influenza virus infection. However, the inflammatory risk factors contributing to HTG in patients with severe influenza have yet to be elucidated. Materials and methods Plasma and bronchoalveolar lavage fluid (BALF) samples were collected from 33 patients with severe influenza (n = 26 control patients with normal serum triglyceride levels and n = 7 HTG patients with serum triglycerides >2.3 mM). Levels of 45 putative inflammatory risk factors were quantitated using a commercial enzyme-linked immunosorbent assay kit. Results Plasma levels of interferon (IFN)-γ, interleukin (IL)-18, IL-1 receptor antagonist (IL-1RA), monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, hepatocyte growth factor, stem cell factor, and vascular endothelial growth factor A were significantly higher in HTG patients compared with control patients. BALF samples from HTG patients contained significantly higher levels of IL-1RA and lower levels of IFN-γ-inducible protein-10. Conclusion HTG in patients with severe influenza is associated with alterations in several inflammatory risk factors. Our results provide new insights that may enable more effective clinical management of severe influenza combined with HCT.
Thyroid hormone receptors are required for the melatonin‐dependent control of Rfrp gene expression in mice

Mammals adapt to seasons using a neuroendocrine calendar defined by the photoperiodic change in the nighttime melatonin production. Under short photoperiod, melatonin inhibits the pars tuberalis production of TSHβ, which, in turn, acts on tanycytes to regulate the deiodinase 2/3 balance resulting in a finely tuned seasonal control of the intra‐hypothalamic thyroid hormone T3. Despite the pivotal role of this T3 signaling for synchronizing reproduction with the seasons, T3 cellular targets remain unknown. One candidate is a population of hypothalamic neurons expressing Rfrp, the gene encoding the RFRP‐3 peptide, thought to be integral for modulating rodent's seasonal reproduction. Here we show that nighttime melatonin supplementation in the drinking water of melatonin‐deficient C57BL/6J mice mimics photoperiodic variations in the expression of the genes Tshb, Dio2, Dio3, and Rfrp, as observed in melatonin‐proficient mammals. Notably, we report that this melatonin regulation of Rfrp expression is no longer observed in mice carrying a global mutation of the T3 receptor, TRα, but is conserved in mice with a selective neuronal mutation of TRα. In line with this observation, we find that TRα is widely expressed in the tanycytes. Altogether, our data demonstrate that the melatonin‐driven T3 signal regulates RFRP‐3 neurons through non‐neuronal, possibly tanycytic, TRα.
Bacteria elevate extracellular adenosine to exploit host signaling for blood-brain barrier disruption

ABSTRACT Bacterial meningitis remains a substantial cause of mortality worldwide and survivors may have severe lifelong disability. Although we know that meningeal bacterial pathogens must cross blood-central nervous system (CNS) barriers, the mechanisms which facilitate the virulence of these pathogens are poorly understood. Here, we show that adenosine from a surface enzyme (Ssads) of Streptococcus suis facilitates this pathogen’s entry into mouse brains. Monolayer translocation assays (from the human cerebrovascular endothelium) and experiments using diverse inhibitors and agonists together demonstrate that activation of the A1 adenosine receptor signaling cascade in hosts, as well as attendant cytoskeleton remodeling, promote S. suis penetration across blood-CNS barriers. Importantly, our additional findings showing that Ssads orthologs from other bacterial species also promote their translocation across barriers suggest that exploitation of A1 AR signaling may be a general mechanism of bacterial virulence.
Hepatoprotective Effects of the Triterpenes Isolated from the Stem Bark of Diospyros cordifolia Roxb

The hepatoprotective activity of the chemical constituents isolated from the stem bark of Diospyros cordifolia Roxb. was screened on male Wister strain rats against carbon tetrachloride induced toxic hepatitis. Significant hepatoprotective activity was observed in the active constituents, ursolic acid, lupeol and betulin isolated from the petroleum ether extract of stem bark. The hepatoprotective activity was assessed by the assay of liver function parameters viz. serum total bilirubin, total protein, alanine aminotransaminase, aspartate aminotransaminase and alkaline phosphatase activities. Histopathological studies also evidenced the hepatoprotective effect of the tested constituents. Ursolic acid showed more significant hepatoprotective activity than lupeol and betulin. The results have comparison with the standard hepatoprotective drug silymarin.
Acute effects of body-weight resistance exercises on blood pressure and glycemia in middle-aged adults with hypertension

ABSTRACT Objective The purpose of the present study was to evaluate the acute effects of single session of body-weight resistance exercises on blood pressure (BP) and glycemia in middle-aged adults with hypertension. Methods Twenty-three participants took part in this trial with crossover design and performed two experimental sessions in a random order: Body-weight resistance exercise session (BWR) and a control session without exercise. BWR was composed of four exercises: inverted row, squat, , and sit-ups. The participants performed 3 sets of 30 s, in which they were instructed to perform as much repetitions as possible and as fast as possible. After each session, BP and glycemia were measured continuously for 60 min. Results Systolic BP decreased after BWR when compared with control at post 45ʹ: −7 (95%CI:-11 to −2) mmHg, p = . 003 and post60ʹ: −7 (95%CI:-12 to −3) mmHg, p = . 003. Diastolic BP decreased after BWR when compared with control at post 15ʹ: −6 (95%CI:-9 to −3) mmHg, p < . 001; post 30ʹ: −6 (95%CI:-9 to −2) mmHg, p = . 001; post45ʹ: −5 (95%CI:-9 to −2) mmHg, p = . 005; and post60ʹ: −6 (95%CI: −8 to −3) mmHg, p < . 001. No significant difference was found in glycemia between BWR and control sessions. Conclusion BWR acutely reduces BP in middle-aged adults with hypertension without effects on usual glycemia responses. This alternative form of resistance training could facilitate access, adherence, and reduce health costs related to exercise programs.
Delta-like ligand 4-mediated Notch signaling controls proliferation of second heart field progenitor cells by regulating Fgf8 expression

ABSTRACT The role played by the Notch pathway in cardiac progenitor cell biology remains to be elucidated. Delta-like ligand 4 (Dll4), the arterial-specific Notch ligand, is expressed by second heart field (SHF) progenitors at time-points that are crucial in SHF biology. Dll4-mediated Notch signaling is required for maintaining an adequate pool of SHF progenitors, such that Dll4 knockout results in a reduction in proliferation and an increase in apoptosis. A reduced SHF progenitor pool leads to an underdeveloped right ventricle (RV) and outflow tract (OFT). In its most severe form, there is severe RV hypoplasia and poorly developed OFT resulting in early embryonic lethality. In its milder form, the OFT is foreshortened and misaligned, resulting in a double outlet right ventricle. Dll4-mediated Notch signaling maintains Fgf8 expression by transcriptional regulation at the promoter level. Combined heterozygous knockout of Dll4 and Fgf8 demonstrates genetic synergy in OFT alignment. Exogenous supplemental Fgf8 rescues proliferation in Dll4 mutants in ex-vivo culture. Our results establish a novel role for Dll4-mediated Notch signaling in SHF biology. More broadly, our model provides a platform for understanding oligogenic inheritance that results in clinically relevant OFT malformations. Summary: Dll4-mediated Notch signaling ensures an adequate pool of second heart field progenitors during heart development by maintaining levels of key proteins, such as Fgf8.
Associations between maternal lifetime stressors and negative events in pregnancy and breast milk-derived extracellular vesicle microRNAs in the programming of intergenerational stress mechanisms (PRISM) pregnancy cohort

ABSTRACT Maternal stress is associated with adverse child health. Breast milk microRNAs encapsulated in extracellular vesicles (EVs) are involved in mother-infant biochemical communication during early-life programming. We leverage the PRogramming of Intergenerational Stress Mechanisms (PRISM) pregnancy cohort to investigate associations between maternal stress and breast milk EV-microRNAs. Lifetime stress and negative life events (NLEs) during pregnancy were assessed using the Life Stressor Checklist-Revised (LSCR) and the Crisis in Family Systems-Revised surveys, respectively. RNA was extracted from breast milk EVs (N = 80; collected 6.1 ± 5.9 weeks postnatally), and microRNAs were profiled using the TaqMan OpenArray Human miRNA panel. Associations between stress scores and detection (yes/no) of 173 microRNAs identified in 20–80% of samples were assessed using logistic regression; associations with expression levels of 205 EV-microRNAs identified in >50% of samples were assessed using linear regression. In adjusted models, detection of 60 and 44 EV-microRNAs was associated with higher LSCR and NLE scores, respectively (p < 0.05). Expression level of 8 and 17 EV-microRNAs was associated with LSCR and NLE scores, respectively, at our a priori criteria of p < 0.05 and |B regression|>0.2. Enriched KEGG pathways for microRNAs associated with stress scores included fatty acid metabolism and the Hippo signaling pathway. Maternal lifetime stress and NLEs during pregnancy were both associated with detection and expression level of breast milk EV-microRNAs, although associations with microRNA profiles differed between stress measures. Further research is needed to identify biological pathways impacted by associated microRNAs and investigate relationships with child health outcomes. Abbreviations: EV: extracellular vesicle; PRISM: PRogramming of Intergenerational Stress Mechanisms pregnancy cohort; LSCR: Life Stressor Checklist-Revised survey; NLE: negative life event; CRISYS-R: Crisis in Family Systems-Revised survey; KEGG: Kyoto Encyclopaedia of Genes and Genomes; NYC: New York City; SD: standard deviation; IQR: interquartile range; Cq: relative cycle threshold values; PCA: principal component analysis
Short bowel syndrome and the impact on patients and their families: a qualitative study.

BACKGROUND Short bowel syndrome (SBS) is a malabsorptive condition that can result in intestinal failure (SBS-IF). Many patients with SBS-IF require home parenteral nutrition (PN) for survival. However, PN has profound effects on patients and their family members. The present study aimed to understand the lived experience of SBS-IF for patients and their families. METHODS In-depth semi-structured qualitative interviews were conducted with 15 patients with SBS-IF and five adult family members living with someone with SBS-IF. A patient-centric approach was taken, with a patient steering group providing input and guidance to develop the interview guide. Key concepts were identified using thematic analysis of interview transcripts. RESULTS Patients' lives were dominated by having SBS-IF. They described physical impacts that included patient-reported signs and symptoms and physical restrictions comprising of restrictions on daily life, actives of daily living and physical functioning. In addition, they encountered emotional impacts with a plethora of negative feelings and social impacts, such as difficulties socialising and maintaining relationships. Patients coped by adapting their life around SBS-IF, having support and adopting an attitude of gratitude and acceptance. Family members were also affected and, along with patients, appreciated the respite of a night off from infusions. CONCLUSIONS Patients and families face many difficulties with SBS-IF. Healthcare professionals can support patients by facilitating them explore what others have found beneficial; adapting their life around PN, viewing PN with acceptance and trying to cultivate gratitude. Further research into the support required for families may be beneficial.