Miracle-dz/UniFAR-FTUs huggingface dataset:
Impacts of unfavourable lifestyle factors on biomarkers of liver function, inflammation and lipid status

Background Adopting a healthy lifestyle is associated with prolonged life expectancy. The main modifiable lifestyle-related risk factors are hazardous alcohol drinking, smoking, excess body weight and lack of physical activity. Our aim was to estimate the impact of unfavourable lifestyle factors on abnormalities in laboratory tests reflecting liver status, inflammation and lipid metabolism in a population-based cross-sectional study. Methods The study included 22,273 participants (10,561 men, 11,712 women) aged 25–74 years from the National FINRISK Study. Data on alcohol use, smoking, body weight, and physical activity were recorded from structured interviews. The risk scores for the various life style factors were established on a 0–8 scale and used to stratify the population in classes to allow estimates of their joint effects. Serum liver enzymes (GGT, ALT), C-reactive protein (CRP) and lipid profiles were measured using standard laboratory techniques. Results Consistent dose-response relationships were observed between the number of unfavourable risk factors and serum levels of GGT, ALT, CRP, cholesterol, HDL, LDL and triglycerides (p < 0.0005 for linear trend in all comparisons). When compared with those with zero risk factors, the multivariable-adjusted odds ratios (ORs) for abnormalities in all biomarkers were significantly higher in those with a sum of risk score two or more. The most striking increases in ORs in the group with the highest numbers of risk factors were observed among men in serum GGT: 26.6 (12.4–57.0), ALT: 40.3 (5.3–307.8), CRP: 16.2 (7.8–33.7) and serum triglycerides: 14.4 (8.6–24.0). Conclusions The data support the view that the presence of unfavourable life style risk factors is associated with distinct abnormalities in laboratory tests for liver function, inflammation and lipid status. Such biomarkers may prove to be of value in the assessment of interventions aimed at reducing unfavourable risk factors and in helping individuals in long-term maintenance of lifestyle modifications.
Nephroblastomas Show Low Expression of MicroR-204 and High Expression of its Target, the Oncogenic Transcription Factor MEIS1

By comparing several studies we identified a possible deregulation of the transcription factors PBX2 (pre–B-cell leukemia homeobox 2) and one of its binding partners, MEIS1 (Meis homeobox 1) in nephroblastomas. The regulation of MEIS1 is complex, and its expression is known to be influenced by changes of promoter methylation and binding of microRNA-204 (miR-204). Therefore, in our study, we assessed the expression of MEIS1 and PBX2 and the factors regulating expression of MEIS1 in nephroblastomas. MEIS1 and PBX2 messenger RNA (mRNA) and protein levels were investigated by quantitative real-time-polymerase chain reaction (qRT-PCR) and immunohistochemistry. Promoter methylation of MEIS1 was evaluated using a methylation-specific PCR assay. Expression levels of miR-204 were examined by qRT-PCR. Eighteen of 21 nephroblastomas showed a high level of MEIS1 mRNA, and 22 of 26 samples had a specific nuclear protein expression. MicroRNA-204 had a statistically significantly lower expression in all nephroblastomas investigated compared with renal parenchyma, but no change of MEIS1 promoter methylation status was noted. Eleven of 23 nephroblastomas had a high expression of PBX2 mRNA, and 15 of 23 samples had a specific nuclear protein expression was noted. In our study, we demonstrated an expression of MEIS1 and its binding partner PBX2 in most nephroblastomas. The statistically significantly lower expression of miR-204 in all nephroblastomas investigated might point to an involvement of miR-204 in the regulation of MEIS1 in nephroblastomas.
Tackling reservoir siltation by controlled sediment flushing: Impact on downstream fauna and related management issues

Sediment flushing can tackle reservoirs siltation and improve sediment flux through dammed rivers. However, the increase of the sediment loading below the dam can trigger a suite of undesired ecological effects in the downstream river reaches. To limit these drawbacks, sediment flushing can be controlled, by jointly regulating the sediment concentration of the evacuated water and the streamflow in the downstream channel. In this paper, we report on ten controlled sediment flushing operations (CSFOs), carried out between 2006 and 2012 in the central Italian Alps, at four hydropower reservoirs. These CSFOs displayed specific common traits: (i) Limits were set by the local environmental authorities concerning the allowable suspended sediment concentration. (ii) Reservoirs were fully drawn-down, earth-moving equipment was used to dislodge sediment, and the downstream water discharge was increased, compared to baseflow, by operating upstream intakes. (iii) Abiotic and biotic measurements in selected downstream reaches (before, during, and after the CSFOs) represented an integral part of the operations. In contrast, significant differences characterize the hydropower facilities (elevation and storage of reservoirs, in particular) as well as the basic CSFOs parameters (i.e., season, duration, mass and grain-size of the evacuated sediment, suspended sediment concentration). The macroinvertebrate assemblages resulted noticeably impacted by the CSFOs. In the short term, a significant density drop was observed, slightly influenced by the extent of the perturbation. In contrast, the latter appeared to control the assemblages contraction in terms of richness, according to the different sensitivity to sediment stress of the different taxa. The time employed to recover pre-CSFO standard ranged from few months to just under one year, and the related patterns would seem mostly correlated to the flushing season and to further site specificities. The density of trout populations was impacted as well, thus suggesting the adoption of mitigating strategies as removal by electrofishing before, and repopulation after the CSFO.
Absent Aortic Valve in DiGeorge Syndrome

A 20-week-old fetus with the 22q11.2 deletion characteristic of DiGeorge syndrome is described with vertebral segmentation abnormalities and complex cardiovascular anomalies including an absent aortic valve. This is only the second known case of absent aortic valve in association with DiGeorge syndrome. We discuss the association of absent aortic valve with other conotruncal defects and the utility of fetal echocardiography in the diagnosis of DiGeorge syndrome.
Immunopathology and Infectious Disease Islet-Cell-Specific T Cells Can Use Different Homing Mechanisms to Infiltrate and Destroy Pancreatic Islets

Organ infiltration by T cells depends on the adhesion molecules expressed in these sites and on homing receptors expressed by the T cells. Here, we have studied which form of priming can enable T cells to home to pancreatic islets. To this end, we have used transgenic mice expressing the model autoantigen ovalbumin in pancreatic islets and transgenic ovalbumin-specific CD4 and CD8 T cells. We demonstrate that these T cells were imprinted with homing receptor patterns characteristic for the site of priming, such as 4 7 integrin for mucosal antigen delivery or functionally active 4 1 integrin for islet autoantigens. The adhesion molecules corresponding to these receptors were found to be constitutively expressed in islets, enabling T cells bearing these receptors to infiltrate the islets and to cause diabetes. Disease was prevented only by blockade of the endothelial adhesion molecule, ligand of homing receptors with which the T cells were imprinted. Thus, different priming locations induced different homing mechanisms, allowing T cells to target the islets. This may contribute to the susceptibility of islets to T-cell-mediated attack. Furthermore, it may pertain to the design of adhesion-modulating therapies alone or in combination with external autoantigen administration. (Am J Pathol 2007, 170:240–250; DOI: 10.2353/ajpath.2007.060142)
HIV/AIDS Among Injecting Drug Users: A review on Epidemiology and Management of Occupational Exposure in Iranian Health Network Setting

Context: Human Immunodeficiency Virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) concentrated in injecting drug users (IDUs) is a major public health in Iran as well as throughout the world. Health care workers (HCW) are occupationally at the risk of HIV infection. The aim of this article is to review the information about the IDUs, epidemiology, diagnosis, natural course of infection, immunopathogenesis, and occupational risks associated with managing HIV in the health care workplace. Evidence Acquisition: Information obtained from previous investigation on HIV infection has yielded a better knowledge about HIV. Results: Because HCWs are at the risk of HIV infection from IDUs attending the health care units, knowledge about preventive strategy and the efficacy of post exposure anti-viral therapy enables general physicians to manage these every moment events. Conclusions: Based on existing data, HIV infection surveillance, performance of standard precaution, and post exposure prophylaxis with anti-retroviral drugs outlined in this review article represent reasonable interim approaches to this complex problem.
Posterior transpetrosal approach to aneurysms of the basilar trunk and vertebrobasilar junction

✓ Aneurysms of the basilar trunk and vertebrobasilar junction represent an exceptional challenge to the neurosurgeon. Surgical access to these deep and confined lesions is hampered by the direct proximity of highly vulnerable neural structures such as the brainstem and cranial nerves, as well as by the structure of the petrous bone, which blocks direct surgical approach to these aneurysms. A number of surgical tactics consisting of different supra- and infratentorial approaches have been applied over the years to gain access to these treacherous lesions. Only recently have lateral approaches, such as the anterior transpetrosal, the retrolabyrinthine—transsigmoidal, and the combined supra/infratentorial—posterior transpetrosal approaches, directed through parts of the petrous bone, been reported for surgery of basilar trunk and vertebrobasilar junction aneurysms. Because detailed reports of direct operative intervention using the transpetrosal route for these rare and difficult lesions are scarce, the auth.
Prevalence and risk factors of drug-related hospitalizations in multimorbid patients admitted to an internal medicine ward

Background Knowledge of risk factors for drug-related hospitalizations (DRHs) is limited. Aim To examine the prevalence of DRHs and the relationships between DRHs and various variables in multimorbid patients admitted to an internal medicine ward. Methods Multimorbid patients ≥ 18 years, using minimum of four regular drugs from minimum two therapeutic classes, were included from the Internal Medicine ward, Oslo University Hospital, Norway, from August 2014 to March 2016. Clinical pharmacists prospectively conducted medicines reconciliations and reviews to reveal drug-related problems (DRPs). Blinded for identified DRPs, an interdisciplinary group retrospectively made comprehensive, clinical assessments of each patient case to classify hospitalizations as drug-related (DRH) or non-drug-related (non-DRH). Age, sex distribution, Charlson Comorbidity Index (CCI), renal function, aberrant genotype frequencies, body-mass index, number of drugs, proportion of patients which received assistance for drug administration from the home care service, and/or through multidose-dispensed drugs, and occurrence of specific DRP subgroups, were compared separately between patients with DRHs versus non-DRHs, followed by multiple logistic regression analysis. Results Hospitalizations were classified as drug-related in 155 of the 404 included patients (38%). Factors significantly associated with DRHs were occurrence of adverse effect DRPs (adjusted odds ratio (OR) 3.3, 95% confidence interval (CI) 1.4–8.0), adherence issues (OR 2.9, 1.1–7.2), home care (OR 1.9, 1.1–3.5), drug monitoring DRPs (OR 1.9, 1.2–3.0), and CCI score ≥6 (OR 0.33, 0.14–0.77). Frequencies of aberrant genotypes did not differ between the patient groups, but in 41 patients with DRHs (26.5%), gene-drug interactions influenced the assessments of DRHs. Conclusion DRHs are prevalent in multimorbid patients with adverse effect DRPs and adherence issues as the most important risk factors.
Increasing the translation of mouse models of MERS coronavirus pathogenesis through kinetic hematological analysis

Newly emerging viral pathogens pose a constant and unpredictable threat to human and animal health. Coronaviruses (CoVs) have a penchant for sudden emergence, as evidenced by severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV) and most recently, swine acute diarrhea syndrome coronavirus (SADS-CoV). Small animal models of emerging viral pathogenesis are crucial to better understand the virus and host factors driving disease progression. However, rodent models are often criticized for their limited translatability to humans. The complete blood count is the most ordered clinical test in the United States serving as the cornerstone of clinical medicine and differential diagnosis. We recently generated a mouse model for MERS-CoV pathogenesis through the humanization of the orthologous entry receptor dipeptidyl peptidase 4 (DPP4). To increase the translatability of this model, we validated and established the use of an automated veterinary hematology analyzer (VetScan HM5) at biosafety level 3 for analysis of peripheral blood. MERS-CoV lung titer peaked 2 days post infection concurrent with lymphopenia and neutrophilia in peripheral blood, two phenomena also observed in MERS-CoV infection of humans. The fluctuations in leukocyte populations measured by Vetscan HM5 were corroborated by standard flow cytometry, thus confirming the utility of this approach. Comparing a sublethal and lethal dose of MERS-CoV in mice, analysis of daily blood draws demonstrates a dose dependent modulation of leukocytes. Major leukocyte populations were modulated before weight loss was observed. Importantly, neutrophil counts on 1dpi were predictive of disease severity with a lethal dose of MERS-CoV highlighting the predictive value of hematology in this model. Taken together, the inclusion of hematological measures in mouse models of emerging viral pathogenesis increases their translatability and should elevate the preclinical evaluation of MERS-CoV therapeutics and vaccines to better mirror the complexity of the human condition.
Internalin AB-expressing recombinant Lactobacillus casei protects Caco-2 cells from Listeria monocytogenes-induced damages under simulated intestinal conditions

Background Listeria monocytogenes is an intracellular foodborne pathogen that employs a number of strategies to survive challenging gastrointestinal conditions. It proliferates in the gut and subsequently causes listeriosis in high-risk individuals. Therefore, inhibition of its adherence to the intestinal receptors is crucial in controlling its infection. In this study, the effect of our previously developed recombinant Lactobacillus casei strain expressing invasion protein, Internalin AB of L. monocytogenes (LbcInlAB) on epithelial infection processes of the latter under simulated intestinal conditions was investigated. Materials and methods The confluent Caco-2 cell monolayer was pre-exposed to different L. casei strains at a multiplicity of exposure (MOE) of 10 for various periods before infection with L. monocytogenes at a multiplicity of infection (MOI) of 10 under simulated intestinal conditions. Subsequently, L. monocytogenes adhesion, invasion, and translocation, cytotoxicity and impact on tight junction integrity of the Caco-2 cells were analyzed. Results Under the simulated gastrointestinal condition, LbcInlAB showed a significant increase (p<0.0001) in adherence to, invasion and translocation through the Caco-2 cells when compared with the wild type strain. Although LbcInlAB strain exhibited enhanced inhibition of L. monocytogenes, it was not able to displace L. monocytogenes cells already attached to the monolayer. Additionally, pre-exposure to LbcInlAB reduced L. monocytogenes-mediated cytotoxicity and protected the tight junction barrier function. Conclusion The recombinant L. casei expressing InlAB shows potential for use as a prophylactic intervention strategy for targeted control of L. monocytogenes during the intestinal phase of infection.
Determining Provider Needs for Respite Training, Results of an Alabama Survey

The Alabama Lifespan Respite Resource Network™ enhances respite services for family caregivers. University evaluators conducted a statewide assessment of respite providers using multiple formats. The purpose was to determine met and unmet needs for respite training among providers serving family caregivers of individuals with disabilities and chronic illnesses. A total of 317 respite providers attempted and 191 completed survey items, revealing respite experience, disabilities and chronic illnesses, areas of difficulty, prior training and confidence, training needs and preferences. Results will be used by a state Network to match content and delivery of training to providers’ needs. Respite providers have important roles to play, sharing information about respite services and providers, advocating for caregiver eligibility to receive services, and participating in training paid and volunteer providers.
Home rehabilitation supported by a wearable soft-robotic device for improving hand function in older adults: A pilot randomized controlled trial

Background New developments, based on the concept of wearable soft-robotic devices, make it possible to support impaired hand function during the performance of daily activities and intensive task-specific training. The wearable soft-robotic ironHand glove is such a system that supports grip strength during the performance of daily activities and hand training exercises at home. Design This pilot randomized controlled clinical study explored the effect of prolonged use of the assistive ironHand glove during daily activities at home, in comparison to its use as a trainings tool at home, on functional performance of the hand. Methods In total, 91 older adults with self-perceived decline of hand function participated in this study. They were randomly assigned to a 4-weeks intervention of either assistive or therapeutic ironHand use, or control group (received no additional exercise or treatment). All participants performed a maximal pinch grip test, Box and Blocks test (BBT), Jebsen-Taylor Hand Function Test (JTHFT) at baseline and after 4-weeks of intervention. Only participants of the assistive and therapeutic group completed the System Usability Scale (SUS) after the intervention period. Results Participants of the assistive and therapeutic group reported high scores on the SUS (mean = 73, SEM = 2). The therapeutic group showed improvements in unsupported handgrip strength (mean Δ = 3) and pinch strength (mean Δ = 0.5) after 4 weeks of ironHand use (p≤0.039). Scores on the BBT and JTHFT improved not only after 4 weeks of ironHand use (assistive and therapeutic), but also in the control group. Only handgrip strength improved more in the therapeutic group compared to the assistive and control group. No significant correlations were found between changes in performance and assistive or therapeutic ironHand use (p≥0.062). Conclusion This study showed that support of the wearable soft-robotic ironHand system either as assistive device or as training tool may be a promising way to counter functional hand function decline associated with ageing.
Molecular Pathogenesis of Genetic and Inherited Diseases Defect of Hepatocyte Growth Factor Activator Inhibitor Type 1 / Serine Protease Inhibitor , Kunitz Type 1 ( Hai-1 / Spint 1 ) Leads to Ichthyosis-Like Condition and Abnormal Hair Development in Mice

From the Section of Oncopathology and Regenerative Biology,* Department of Pathology, the Section of Surgical Oncology and Regulation of Organ Function, Department of Surgery, and the Departments of Anatomy and Dermatology, Faculty of Medicine, University of Miyazaki, Miyazaki, and the Center for Animal Resources and Development, Institute of Resources Development and Analysis, Kumamoto University, Kumamoto, Japan
The effect of Helicobacter pylori infection and different H. pylori components on the proliferation and apoptosis of gastric epithelial cells and fibroblasts

Background Helicobacter pylori colonizes the human gastric mucosa, causing chronic inflammation, peptic ulcers and gastric cancer. A cascade of harmful processes results from the interaction of these bacteria with the gastric epithelium. Aim To investigate these processes in terms of upregulation of oxidative stress and cell apoptosis and downregulation of the pro-regenerative activity of cells. Methods We employed an in vivo guinea pig model at 7 or 28 days postinoculation with H. pylori, corresponding to an acute or chronic stage of infection, respectively, and an in vitro model of guinea pig primary gastric epithelial cells and fibroblasts treated with bacterial components: glycine acid extract (GE), urease subunit A (UreA), cytotoxin-associated gene A protein (CagA) and lipopolysaccharide (LPS). Cells were evaluated for metabolic activity (MTT reduction), myeloperoxidase (MPO) and metalloproteinase (MMP-9) secretion, lipid peroxidation (4-hydroxynonenal (4HNE)), migration (wound healing), proliferation (Ki-67 antigen) and cell apoptosis (TUNEL assay; Bcl-xL, Bax, Bcl-2 expression; caspase 3 cleavage). Results Significant infiltration of the gastric mucosa by inflammatory cells in vivo in response to H. pylori was accompanied by oxidative stress and cell apoptosis, which were more intense 7 than 28 days after inoculation. The increase in cell proliferation was more intense in chronic than acute infection. H. pylori components GE, CagA, UreA, and LPS upregulated oxidative stress and apoptosis. Only H. pylori LPS inhibited cell migration and proliferation, which was accompanied by the upregulation of MMP-9. Conclusions H. pylori infection induces cell apoptosis in conjunction with increased oxidative stress. Elevated apoptosis protects against deleterious inflammation and neoplasia; however, it reduces cell integrity. Upregulation of cell migration and proliferation in response to injury in the milieu of GE, CagA or UreA facilitates tissue regeneration but increases the risk of neoplasia. By comparison, downregulation of cell regeneration by H. pylori LPS may promote chronic inflammation.
Plasma ApoE elevations are associated with NAFLD: The PREVEND Study

Non-alcoholic fatty liver disease (NAFLD) is featured by increased plasma very low density lipoproteins (VLDL). The extent to which plasma apolipoprotein E (ApoE) levels are elevated in NAFLD is unclear. We determined whether plasma ApoE is elevated in subjects with suspected NAFLD. Plasma ApoE and genotypes were determined in 6,762 participants of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort. A Fatty Liver Index (FLI) ≥ 60 was used as a proxy of NAFLD. A total of 1,834 participants had a FLI ≥ 60, which coincided with increased triglycerides, non-HDL cholesterol, ApoB and ApoE (all P<0.001). In multivariable linear regression analysis, plasma ApoE levels were positively associated with an elevated FLI when taking account of ApoE genotypes and other clinical and laboratory covariates (fully adjusted model: β = 0.201, P<0.001). Stratified analysis for ApoE genotypes (ApoE ε3ε3 homozygotes, ApoE ε2 carriers, and ApoE ε3ε4 and ε4ε4 carriers combined), also showed positive associations of plasma ApoE levels with an elevated FLI in each group (all P<0.001). In conclusion, it is suggested that NAFLD is characterized by increased plasma ApoE levels, even when taking account of the various ApoE genotypes. Increased plasma ApoE may contribute to altered VLDL metabolism and to increased atherosclerosis susceptibility in NAFLD.