Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Epidemiology of Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus in Wild, Captive and Laboratory Rats: Effect of Habitat on the Nasal S. aureus Population

Rats are a reservoir of human- and livestock-associated methicillin-resistant Staphylococcus aureus (MRSA). However, the composition of the natural S. aureus population in wild and laboratory rats is largely unknown. Here, 144 nasal S. aureus isolates from free-living wild rats, captive wild rats and laboratory rats were genotyped and profiled for antibiotic resistances and human-specific virulence genes. The nasal S. aureus carriage rate was higher among wild rats (23.4%) than laboratory rats (12.3%). Free-living wild rats were primarily colonized with isolates of clonal complex (CC) 49 and CC130 and maintained these strains even in husbandry. Moreover, upon livestock contact, CC398 isolates were acquired. In contrast, laboratory rats were colonized with many different S. aureus lineages—many of which are commonly found in humans. Five captive wild rats were colonized with CC398-MRSA. Moreover, a single CC30-MRSA and two CC130-MRSA were detected in free-living or captive wild rats. Rat-derived S. aureus isolates rarely harbored the phage-carried immune evasion gene cluster or superantigen genes, suggesting long-term adaptation to their host. Taken together, our study revealed a natural S. aureus population in wild rats, as well as a colonization pressure on wild and laboratory rats by exposure to livestock- and human-associated S. aureus, respectively.
Evidence of detrimental effects of prenatal alcohol exposure on offspring birthweight and neurodevelopment from a systematic review of quasi-experimental studies

Abstract Background Systematic reviews of prenatal alcohol exposure effects generally only include conventional observational studies. However, estimates from such studies are prone to confounding and other biases. Objectives To systematically review the evidence on the effects of prenatal alcohol exposure from randomized controlled trials (RCTs) and observational designs using alternative analytical approaches to improve causal inference. Search strategy Medline, Embase, Web of Science, PsychINFO from inception to 21 June 2018. Manual searches of reference lists of retrieved papers. Selection criteria RCTs of interventions to stop/reduce drinking in pregnancy and observational studies using alternative analytical methods (quasi-experimental studies e.g. Mendelian randomization and natural experiments, negative control comparisons) to determine the causal effects of prenatal alcohol exposure on pregnancy and longer-term offspring outcomes in human studies. Data collection and analysis One reviewer extracted data and another checked extracted data. Risk of bias was assessed using customized risk of bias tools. A narrative synthesis of findings was carried out and a meta-analysis for one outcome. Main results Twenty-three studies were included, representing five types of study design, including 1 RCT, 9 Mendelian randomization and 7 natural experiment studies, and reporting on over 30 outcomes. One study design–outcome combination included enough independent results to meta-analyse. Based on evidence from several studies, we found a likely causal detrimental role of prenatal alcohol exposure on cognitive outcomes, and weaker evidence for a role in low birthweight. Conclusion None of the included studies was judged to be at low risk of bias in all domains, results should therefore be interpreted with caution. Systematic review registration This study is registered with PROSPERO, registration number CRD42015015941
The Effects of Early-Onset Pre-Eclampsia on Placental Creatine Metabolism in the Third Trimester

Creatine is a metabolite important for cellular energy homeostasis as it provides spatio-temporal adenosine triphosphate (ATP) buffering for cells with fluctuating energy demands. Here, we examined whether placental creatine metabolism was altered in cases of early-onset pre-eclampsia (PE), a condition known to cause placental metabolic dysfunction. We studied third trimester human placentae collected between 27–40 weeks’ gestation from women with early-onset PE (n = 20) and gestation-matched normotensive control pregnancies (n = 20). Placental total creatine and creatine precursor guanidinoacetate (GAA) content were measured. mRNA expression of the creatine synthesizing enzymes arginine:glycine aminotransferase (GATM) and guanidinoacetate methyltransferase (GAMT), the creatine transporter (SLC6A8), and the creatine kinases (mitochondrial CKMT1A & cytosolic BBCK) was assessed. Placental protein levels of arginine:glycine aminotransferase (AGAT), GAMT, CKMT1A and BBCK were also determined. Key findings; total creatine content of PE placentae was 38% higher than controls (p < 0.01). mRNA expression of GATM (p < 0.001), GAMT (p < 0.001), SLC6A8 (p = 0.021) and BBCK (p < 0.001) was also elevated in PE placentae. No differences in GAA content, nor protein levels of AGAT, GAMT, BBCK or CKMT1A were observed between cohorts. Advancing gestation and birth weight were associated with a down-regulation in placental GATM mRNA expression, and a reduction in GAA content, in control placentae. These relationships were absent in PE cases. Our results suggest PE placentae may have an ongoing reliance on the creatine kinase circuit for maintenance of cellular energetics with increased total creatine content and transcriptional changes to creatine synthesizing enzymes and the creatine transporter. Understanding the functional consequences of these changes warrants further investigation.
Use of three pins in Gamma Knife stereotactic radiosurgery for brain metastases.

Purpose We present our institutional experience in treating brain metastases with GK-SRS and a headframe fixed to the skull with only 3 pins to avoid collisions between the headframe and the Gamma Knife (GK) machine. Methods and materials Among 3500 consecutive patients who received GK-SRS in 2011-2017, 50 had 1 of the 2 anterior pins removed immediately before treatment of ≥1 brain lesion. Endpoints were local control, dosimetric parameters, and toxicity. Results Median follow-up time for the 49 patients with follow-up was 7.0 months (range 0.2-57.0). Median number of lesions treated per session was 6 (range 1-18); a median 1 lesion was treated with 3-pin fixation (range 1-2) and a median 5 lesions treated with 4-pin fixation (range 0-17) during the same session. Lesions treated with 3-pin fixation were in the occipital lobe (n=41), cerebellum (n=9), or temporal lobe (n=1). No local failures were noted. The sole grade 2 toxicity (partial seizure) was attributed to treatment of a 4-pin-fixed lesion. Except for gradient index, dosimetry did not vary for lesions treated with 3-pin versus 4-pin fixation. Conclusions Treating brain metastases with 3-pin fixation did not compromise treatment outcome and is a good option for posterior brain metastases that cannot otherwise be treated with 4-pin GK-SRS.
Bioactives from Agri-Food Wastes: Present Insights and Future Challenges

Sustainable utilization of agri-food wastes and by-products for producing value-added products (for cosmetic, pharmaceutical or food industrial applications) provides an opportunity for earning additional income for the dependent industrial sector. Besides, effective valorisation of wastes/by-products can efficiently help in reducing environmental stress by decreasing unwarranted pollution. The major focus of this review is to provide comprehensive information on valorisation of agri-food wastes and by-products with focus laid on bioactive compounds and bioactivity. The review covers the bioactives identified from wastes and by-products of plants (fruits, exotic fruits, vegetables and seeds), animals (dairy and meat) and marine (fish, shellfish seaweeds) resources. Further, insights on the present status and future challenges of sustainably utilizing agri-food wastes/by-products for value addition will be highlighted.
Interpersonal functioning, support, and change in early-onset bipolar disorder: a transcendental phenomenological study of emerging adults

Abstract Background Early-onset bipolar disorder (EOBD) diagnoses have increased, yet much remains to be understood about its phenomenology. Research and treatment models developed for adult-onset bipolar disorder have largely overlooked qualitative inquiries and adolescent developmental considerations that influence course of illness. Aim The purpose of the current study was to obtain an understanding of the lived experience of interpersonal relationships and EOBD during adolescence through the retrospective report of emerging adults. Methods This study utilized a transcendental phenomenological design. A purposive sample of eight participants ages 18–25 participated in semi-structured interviews that explored the experience of interpersonal relationships and EOBD throughout adolescence. Results Participants described their experiences across three broad themes: managing and coping with EOBD; effect of EOBD on relationships; and change and uncertainty. Sub-themes include knowledge and denial of illness, involvement of others in treatment, support, difficulty maintaining social functioning, isolation and secrecy, and changes in relationships. Conclusions Participants characterized adolescence as a period of constant, simultaneous challenges in symptom management, maintaining social functioning, and concurrent changes in family and peer relationships that provide interpersonal support. Future qualitative studies should explore the implications of normative social development and family functioning for the course of illness and treatment outcomes.
A model of independence for

This article outlines the work undertaken to find a suitable model for planning respite care for children with disabilities. The model ‘This is Me’ and the informal life events assessment tool ‘Hello, This is Me! ’, which supports it, are described. The use of a person-centred care planning system is well documented in the care of adults with learning disabilities (Sanderson, 1997). This process should begin at the start of a person’s life, as recommended by The Children Act 1989, and the documents ‘Signposts for Success’ (NHS Executive, 1998) and ‘Don’t Forget Us’ (Mental Health Foundation, 1997). The article describes the development of a person-centred approach to respite care which is underpinned with a basic care premise.
The association between low vitamin D levels and suicide attempts in adolescents.

BACKGROUND Psychiatric disorders are the most common cause of suicide attempts. Some studies have shown there is a relationship between low vitamin D levels and psychiatric disorders. In this study, we examined the relationship between suicidal behavior and vitamin D levels in adolescents. METHOD This study included 215 patients who presented to the pediatric emergency department due to a suicide attempt (patient group) and 200 healthy individuals (control group). Demographic and clinical features of both groups were recorded, and serum vitamin D, calcium, and phosphorus levels were measured. The groups were compared in terms of these factors. All data were analyzed using the SPSS 20.0 (SPSS Inc., Illinois, USA) software program. RESULTS The mean vitamin D level was 19.4 ± 10 ng/mL in the control group and 12.3 ± 6 ng/mL in the patient group (t = 8.8 and P = .01). The mean serum total calcium level was 9.9 ± 0.3 mg/dL in the control group and 9.4 ± 0.5 mg/dL in the patient group (P < .01). CONCLUSIONS Vitamin D deficiency, which is a treatable condition, may be one of the causes of suicidal behavior in adolescents. Therefore, we believe that physicians who treat adolescents should consider vitamin D levels in routine examinations.
Endothelial Response Boosted by Platelet Lysate: The Involvement of Calcium Toolkit

Wound repair is a dynamic process during which crucial signaling pathways are regulated by growth factors and cytokines released by several kinds of cells directly involved in the healing process. However, the limited applications and heterogeneous clinical results of single growth factors in wound healing encouraged the use of a mixture of bioactive molecules such as platelet derivatives for best results in wound repair. An interesting platelet derivative, obtained from blood samples, is platelet lysate (PL), which has shown potential clinical application. PL is obtained from freezing and thawing of platelet-enriched blood samples. Intracellular calcium (Ca2+) signals play a central role in the control of endothelial cell survival, proliferation, motility, and differentiation. We investigated the role of Ca2+ signaling in the PL-driven endothelial healing process. In our experiments, the functional significance of Ca2+ signaling machinery was highlighted performing the scratch wound assay in presence of different inhibitors or specific RNAi. We also pointed out that the PL-induced generation of intracellular ROS (reactive oxygen species) via NOX4 (NADPH oxidase 4) is necessary for the activation of TRPM2 and the resulting Ca2+ entry from the extracellular space. This is the first report of the mechanism of wound repair in an endothelial cell model boosted by the PL-induced regulation of [Ca2+]i.
Diagnostic Values of Inflammatory and Angiogenic Factors for Acute Joint Bleeding in Patients With Severe Hemophilia A

This study was conducted to assess the levels of inflammatory factors and angiogenic factors in patients with severe hemophilia A and evaluate their diagnostic values for acute joint bleeding. This study included a total of 144 patients with severe hemophilia A. Of them, 66 had acute joint bleeding. Ninety healthy volunteers were recruited as control. The levels of leukocytes, monocytes, platelets, hemoglobin, phagocyte migration inhibitory factor (MIF), plasminogen, fibrin/fibrinogen degradation products, d-dimer, and α2 antifibrinolytic enzyme were measured using hematology analyzer. Thrombomodulin, endostatin, intercellular adhesion molecule 1, and vascular endothelial growth factor (VEGF) were assessed using enzyme-linked immunosorbent assay. Logistic regression analysis was performed to analyze the factors affecting acute joint bleeding. Compared with healthy volunteers, the levels of leukocytes, C-reactive protein (CRP), MIF, and VEGF were significantly (P < .05) elevated in the patients with severe hemophilia A and were significantly higher in patients with joint bleeding than in patients with nonbleeding (P < .05). Multivariate analysis showed that CRP and VEGF were independent risk factors for acute joint bleeding (P < .05). The area under the curve, sensitivity, and specificity of CRP for the diagnosis of acute joint bleeding were 0.829, 88.43%, and 67.87%, respectively, and those of VEGF were 0.758, 82.8%, and 68.3%, respectively. The levels of inflammatory factors and angiogenesis factors are elevated in patients with severe hemophilia A and both CRP and VEGF are closely related to acute joint bleeding and may be used as potential biomarkers for predicting acute joint bleeding in patients with severe hemophilia A.
Factors associated with death in bedridden patients in China: A longitudinal study

Background Immobility is common and associated with adverse outcomes in hospitalized patients, especially older people. However, the factors contributing to mortality in bedridden patients are not well known. This study aimed to estimate short-term mortality and analyze risk factors that affect the prognosis of bedridden patients. Methods This was a multicenter study in China involving 23,738 patients admitted to 25 hospitals between November 2015 and June 2016. All-cause mortality was recorded for 90 days after enrollment regardless of whether death occurred before or after discharge. Socio-demographic and clinical information was obtained from an electronic database. Univariate and multivariate Cox regression analysis was used to identify factors associated with mortality. Results In total, 23,738 hospitalized bedridden patients, there were 1,114 (4.7%) observed deaths. The overall mortality rate was therefore 4.7%. Of these, 318 (1.4%) died while hospitalized and 796 (3.4%) after discharge. The univariate Cox regression analysis showed that variables significantly associated with 90-day mortality included total time spent bedridden, urinary tract infection and pulmonary infection (p<0.05). The multivariate Cox regression analysis showed that the independent risk factors for death were age (adjusted hazard ratio [aHR] 1.006, 95% CI 1.000–1.011), and pulmonary infection (aHR 1.439, 95% CI 1.266–1.635). The hazard ratios for mortality were reduced with urinary tract infection and more time spent bedridden. Conclusions The mortality after discharge was significantly higher than mortality in hospital. The factors affecting short-term mortality in bedridden patients included age, time spent bedridden, urinary tract infection and pulmonary infection. This suggests these factors may be potential predictors of mortality in bedridden patients. It is essential for medical staff to improve health education of patients and family members, pay more attention to follow up after discharge and meet care needs at home.
Molecular Hydrogen Metabolism: a Widespread Trait of Pathogenic Bacteria and Protists

Pathogenic microorganisms use various mechanisms to conserve energy in host tissues and environmental reservoirs. One widespread but often overlooked means of energy conservation is through the consumption or production of molecular hydrogen (H2). Here, we comprehensively review the distribution, biochemistry, and physiology of H2 metabolism in pathogens. SUMMARY Pathogenic microorganisms use various mechanisms to conserve energy in host tissues and environmental reservoirs. One widespread but often overlooked means of energy conservation is through the consumption or production of molecular hydrogen (H2). Here, we comprehensively review the distribution, biochemistry, and physiology of H2 metabolism in pathogens. Over 200 pathogens and pathobionts carry genes for hydrogenases, the enzymes responsible for H2 oxidation and/or production. Furthermore, at least 46 of these species have been experimentally shown to consume or produce H2. Several major human pathogens use the large amounts of H2 produced by colonic microbiota as an energy source for aerobic or anaerobic respiration. This process has been shown to be critical for growth and virulence of the gastrointestinal bacteria Salmonella enterica serovar Typhimurium, Campylobacter jejuni, Campylobacter concisus, and Helicobacter pylori (including carcinogenic strains). H2 oxidation is generally a facultative trait controlled by central regulators in response to energy and oxidant availability. Other bacterial and protist pathogens produce H2 as a diffusible end product of fermentation processes. These include facultative anaerobes such as Escherichia coli, S. Typhimurium, and Giardia intestinalis, which persist by fermentation when limited for respiratory electron acceptors, as well as obligate anaerobes, such as Clostridium perfringens, Clostridioides difficile, and Trichomonas vaginalis, that produce large amounts of H2 during growth. Overall, there is a rich literature on hydrogenases in growth, survival, and virulence in some pathogens. However, we lack a detailed understanding of H2 metabolism in most pathogens, especially obligately anaerobic bacteria, as well as a holistic understanding of gastrointestinal H2 transactions overall. Based on these findings, we also evaluate H2 metabolism as a possible target for drug development or other therapies.
AB0704 Pulmonary Embolism in Oligosymptomatic Systemic Sclerosis Patients

Background Systemic Sclerosis (SSc) patients were recently described to have a higher risk of pulmonary embolism (PE) than healthy individuals1. Portuguese expert consensus2 recommends screening for PE when respiratory distress cannot be explained by the presence of cardiovascular or pulmonary interstitial involvement (ILD). Objectives We present our 5-year experience with PE in SSc patients. Methods We included all adult SSc patients submitted to lung ventilation/perfusion scintigraphy (V/Q scan) or CT pulmonary angiography (AngioCT) due to worsening dyspnea/fatigue or isolated reduction of the carbon monoxide diffusing capacity (DLCO), from January 2010 to December 2014. We collected demographic data, functional class according to the World Health Organization (WHO-FC) classification, comorbidities, risk factors for PE and results from AngioCT and V/Q scans. A descriptive statistical analysis was performed. Results Eighteen patients were included: 15 females, with a mean age of 55±14 years and median disease duration 2 (IQR 2.5) years. Nine patients were diagnosed with PE, 8 of which by V/Q scan and 1 using AngioCT. Eight patients had bilateral peripheral multisegmental PE and 1 unisegmental PE. Five PE patients had a WHO-FC of 1-2. Three of the remaining 4 patients with WHO-FC >2 had concomitant extensive ILD, and one patient had pulmonary hypertension. No patient had thrombophilia, previous surgery or cancer. The frequency of hypertension, diabetes, smoking, obesity and dyslipidemia was similar to patients without PE. Anti-topoisomerase positive SSc patients (Anti-topo+) were slightly overrepresented in the PE group (5 vs 2 Anti-topo+ patients without PE). Other disease imunophenotypes were equally distributed between subgroups. Conclusions Oligosymptomatic PE is common in SSc patients. Traditional procoagulant risk factors do not account for this increased risk. Disease-specific risk factors, such as vascular endothelial dysfunction, may be involved. The impact of PE in disease prognosis is yet unknown. References Chung WS, Lin CL, Sung FC, Hsu WH, Yang WT, Lu CC, Kao CH. Systemic sclerosis increases the risks of deep vein thrombosis and pulmonary thromboembolism: a nationwide cohort study. Rheumatology (Oxford). 2014 Sep;53(9):1639-45. doi: 10.1093/rheumatology/keu133. Epub 2014 Apr 8. Grupo de Estudos de Doenças Reumáticas Sistémicas (GEDRESIS). Manual Prático de Esclerose Sistémica. Sociedade Portuguesa de Reumatologia; 2014. Disclosure of Interest None declared
Engulfment and cannibalism drive persistence of chemotherapy-treated tumor cells: can they be targeted?

ABSTRACT The breast tumors that are most difficult to eradicate with chemotherapy have wild-type TP53 and preferentially enter senescence after treatment. One factor contributing to the persistence of senescent cells in residual disease: acquisition of a novel phenotype that allows cannibalism of entire cells and engulfment of other substrates.
Legionella pneumophila balances ubiquitin transglutamination

The effector MavC of the bacterial pathogen Legionella pneumophila catalyzes a noncanonical ubiquitination of the host ubiquitin‐conjugating E2 enzyme UBE2N by crosslinking a glutamine residue of ubiquitin to UBE2N lysine residues via its transglutaminase activity. A new study by Gan et al (2020) reveals that L. pneumophila reverses this noncanonical ubiquitination via its ubiquitin deamidase effector MvcA to allow precise temporal regulation of host signaling during infection.