Miracle-dz/UniFAR-FTUs huggingface dataset:
Salmonella Fimbrial Protein FimH Is Involved in Expression of Proinflammatory Cytokines in a Toll-Like Receptor 4-Dependent Manner

Type 1 fimbriae are proteinaceous filamentous structures present on bacterial surfaces and are mainly composed of the major fimbrial protein subunit FimA and the adhesive protein FimH, which is located at the tip of the fimbrial shaft. Here, we investigated the involvement of type 1 fimbriae in the expression of proinflammatory cytokines in macrophages infected with Salmonella enterica serovar Typhimurium. ABSTRACT Type 1 fimbriae are proteinaceous filamentous structures present on bacterial surfaces and are mainly composed of the major fimbrial protein subunit FimA and the adhesive protein FimH, which is located at the tip of the fimbrial shaft. Here, we investigated the involvement of type 1 fimbriae in the expression of proinflammatory cytokines in macrophages infected with Salmonella enterica serovar Typhimurium. The level of interleukin-1β (IL-1β) mRNA was lower in macrophages infected with fimA or fimH mutant strains than in those infected with wild-type Salmonella. Treatment of macrophages with purified recombinant FimH protein, but not FimA, resulted in the activation of the mitogen-activated protein kinase and nuclear factor κB signaling pathways, leading to the expression of not only IL-1β but also other proinflammatory cytokines, such as IL-6 and tumor necrosis factor alpha. However, FimH carrying an N-terminal region deletion or heat-treated FimH did not show such effects. The expression of FimH-induced IL-1β was inhibited by treatment with the Toll-like receptor 4 (TLR4) inhibitor TAK-242 but not by treatment with polymyxin B, a lipopolysaccharide antagonist. Furthermore, FimH treatment stimulated HEK293 cells expressing TLR4 and MD-2/CD14 but did not stimulate HEK293 cells expressing only TLR4. Collectively, FimH is a pathogen-associated molecular pattern of S. enterica serovar Typhimurium that is recognized by TLR4 in the presence of MD-2 and CD14 and plays a significant role in the expression of proinflammatory cytokines in Salmonella-infected macrophages.
Maternal Executive Function and Sleep Interact in the Prediction of Negative Parenting

ABSTRACT Objective/Background: Poorer executive function (EF) has been implicated in the etiology of negative parenting (e.g., harsh, reactive, intrusive). EF may be affected by good or poor quality sleep, and thus sleep may be involved in negative parenting. In the current exploratory study, we investigated the additive and interactive effects of maternal EF and sleep indicators in the statistical prediction of negative parenting. Patients/Methods: A sample of 241 mothers of 2.5-year-olds (51% girls) completed questionnaires, wore wrist actigraphs for one week, and completed several EF tasks during a laboratory visit. Results/Conclusions: We found that sleep activity (e.g., nighttime waking and movements) interacted with EF in predicting negative parenting practices, such that poorer EF was linked with more negative parenting only in the context of higher levels of night waking. Sleep duration also interacted with EF, such that EF and parenting were no longer associated when sleep durations were short. The findings have implications for incorporating sleep into our understanding of maternal cognitive self-regulation and harsh parenting during early childhood development.
Ovine Models of Congenital Heart Disease and the Consequences of Hemodynamic Alterations for Pulmonary Artery Remodeling

&NA; The natural history of pulmonary vascular disease associated with congenital heart disease (CHD) depends on associated hemodynamics. Patients exposed to increased pulmonary blood flow (PBF) and pulmonary arterial pressure (PAP) develop pulmonary vascular disease more commonly than patients exposed to increased PBF alone. To investigate the effects of these differing mechanical forces on physiologic and molecular responses, we developed two models of CHD using fetal surgical techniques: 1) left pulmonary artery (LPA) ligation primarily resulting in increased PBF and 2) aortopulmonary shunt placement resulting in increased PBF and PAP. Hemodynamic, histologic, and molecular studies were performed on control, LPA, and shunt lambs as well as pulmonary artery endothelial cells (PAECs) derived from each. Physiologically, LPA, and to a greater extent shunt, lambs demonstrated an exaggerated increase in PAP in response to vasoconstricting stimuli compared with controls. These physiologic findings correlated with a pathologic increase in medial thickening in pulmonary arteries in shunt lambs but not in control or LPA lambs. Furthermore, in the setting of acutely increased afterload, the right ventricle of control and LPA but not shunt lambs demonstrates ventricular‐vascular uncoupling and adverse ventricular‐ventricular interactions. RNA sequencing revealed excellent separation between groups via both principal components analysis and unsupervised hierarchical clustering. In addition, we found hyperproliferation of PAECs from LPA lambs, and to a greater extent shunt lambs, with associated increased angiogenesis and decreased apoptosis in PAECs derived from shunt lambs. A further understanding of mechanical force‐specific drivers of pulmonary artery pathology will enable development of precision therapeutics for pulmonary hypertension associated with CHD.
Psychometric properties and feasibility of use of dementia specific quality of life instruments for use in care settings: a systematic review

ABSTRACT Background: Over 400,000 people live in care home settings in the UK. One way of understanding and improving the quality of care provided is by measuring and understanding the quality of life (QoL) of those living in care homes. This review aimed to identify and examine the psychometric properties including feasibility of use of dementia-specific QoL measures developed or validated for use in care settings. Design: Systematic review. Methods: Instruments were identified using four electronic databases (PubMed, PsycINFO, Web of Science, and CINAHL) and lateral search techniques. Searches were conducted in January 2017. Studies which reported on the development and/or validation of dementia specific QoL instruments for use in care settings written in English were eligible for inclusion. The methodological quality of the studies was assessed using the COSMIN checklist. Feasibility was assessed using a checklist developed specifically for the review. Results: Six hundred and sixteen articles were identified in the initial search. After de-duplication, screening and further lateral searches were performed, 25 studies reporting on 9 dementia-specific QoL instruments for use in care home settings were included in the review. Limited evidence was available on the psychometric properties of many instruments identified. Higher-quality instruments were not easily accessible or had low feasibility of use. Conclusions: Few high-quality instruments of QoL validated for use in care home settings are readily or freely available. This review highlights the need to develop a well-validated measure of QoL for use within care homes that is also feasible and accessible.
Hydroxy group requirement for halofuginone-dependent inhibition of muscle fibrosis and improvement of histopathology in the mdx mouse model for Duchenne muscular dystrophy.

In Duchenne muscular dystrophy (DMD), the progressive loss of muscle and its ability to function is associated with significant fibrosis, representing the major disease complication in patients. Halofuginone, a halogenated analog of the naturally occurring febrifugine, has been shown to prevent fibrosis in various animal models, including those of muscular dystrophies. Here, two optically active enantiomers of deoxyhalofuginone-a halofuginone analogue in which the hydroxy group in position 3 was removed from the piperidinyl entity-were evaluated with respect to their effect on muscle histopathology in mdx mice. Male mdx mice were treated with either deoxyhalofuginone (as single enantiomers or in racemic form), or halofuginone, for 10 weeks, starting at the age of 4 weeks. Halofuginone caused a significant reduction in total collagen content, degenerative areas, as well as in utrophin and phosphorylated-Smad3 levels in the mdx diaphragms. However, neither the deoxyhalofuginone enantiomers, nor its racemic form had any effect on these parameters. A positive effect of the deoxyhalofuginone (+)-enantiomer was observed on myofiber diameters; however, it was lesser than that of halofuginone. It is concluded that the hydroxy group plays a key role in halofuginone's effects related to fibrosis in DMD, and points towards the transforming growth factor β/Smad3 signaling pathway being involved in this inhibition. Elucidation of the structure-function relationship of halofuginone, in relation to inhibiting fibrosis in muscular dystrophies, is of the utmost importance for creating the next generation of anti-fibrotic therapies that will be more efficacious and less toxic, hence improving life quality of patients.
Oncocytic poorly differentiated (insular) thyroid carcinoma mimicking metastatic adenocarcinoma. A case report and review of the literature

We report the cytohistologic and immunohistochemical findings of an oncocytic variant of poorly differentiated thyroid carcinoma in a 76‐year old man with a prior history of prostatic adenocarcinoma. The man complained of a palpable nodule in the right thyroid lobe and cervical lymph node. Fine‐needle aspiration (FNA) in both cases yielded solid clusters of cells/insulae, microfollicles, and isolated atypical cells. Considering the patient's past history, an initial diagnosis of metastasis from prostate adenocarcinoma was considered. However, immunohistochemical staining of liquid‐based cytology specimens (Thin‐Prep) showed diffuse positive results for TTF‐1 and thyroglobulin. The patient underwent total thyroidectomy with bilateral neck dissection. Histologic and immunohistochemical evaluation showed a poorly differentiated oncocytic thyroid carcinoma with lymphovascular invasion and lymph node metastases. To our knowledge, this is the first description of the immunocytochemical evaluation of this rare variant of poorly differentiated thyroid carcinoma using FNA and liquid based cytology.
Pengaruh Lama Hipertensi Terhadap Penyakit Jantung Koroner di Poliklinik Kardiologi RSUP. Dr. Mohammad Hoesin Palembang 2012

Penyakit Jantung Koroner (PJK) merupakan penyebab kematian utama di dunia. Menurut World Health Organization (WHO) tahun 2008, diperkirakan 7,3 juta penduduk dunia meninggal akibat PJK. Angka kematian akibat PJK di Indonesia juga terus meningkat dari tahun ke tahun. Hipertensi merupakan faktor risiko penting terjadinya PJK. Deteksi dini dan perawatan hipertensi yang efektif dapat menurunkan angka kematian. Penelitian ini bertujuan untuk mengetahui pengaruh lama hipertensi terhadap PJK di Poliklinik Kardiologi RSUP Dr. Mohammad Hoesin Palembang.Penelitian ini merupakan penelitian observasional analitik dengan desain cross sectional. Sampel penelitian adalah 107 dari 13.396 pasien penyakit jantung hipertensi di Poliklinik Kardiologi RSUP Dr. Mohammad Hoesin Palembang tahun 2012. Hasil penelitian menunjukkan proporsi PJKsebesar 44,9%. Penderita PJK paling banyak adalah laki-laki (72,9%) dan kelompok usia 45â€“64 tahun (75,0%). Penderita PJK paling sering dijumpai dengan keluhan nyeri dada (43,8%) dan lama hipertensi 11â€“15 tahun (47,9%). Sebagian besar pasien menderita hipertensi derajat 1 (47,9%). Kebanyakan pasien memiliki kadar total kolesterol (41,7%), kolesterol LDL (29,2%), kolesterol HDL (41,7%), trigliserida (43,8%), dan gula darah sewaktu (81,3%) yang normal. Hasil analisis menggunakan uji Chi-square menunjukkan ada hubungan antara lama hipertensi dengan PJK ( p= 0,028) dan lama hipertensi 11â€“15 tahun berisiko 2,957 kali menderita PJK dibandingkan lama hipertensi 1â€“10 tahun.Terdapat pengaruh lama hipertensi terhadap PJK, semakin lama hipertensi maka semakin tinggi risiko terjadinya PJK.
Significant differences in T cell receptor repertoires in lung adenocarcinomas with and without epidermal growth factor receptor mutations

Recent clinical trials of non‐small cell lung cancer with immune checkpoint inhibitors revealed that patients with epidermal growth factor receptor (EGFR) mutations had more unfavorable outcomes compared with those with wild‐type EGFR. However, the underlying mechanism for the link between EGFR mutations and immune resistance remains unclear. We performed T cell receptor (TCR) repertoire analysis of resected lung adenocarcinoma tissues with and without EGFR mutations to investigate the characteristics of TCR repertoires. We collected a total of 39 paired (normal and tumor) lung tissue samples (20 had EGFR mutations) and conducted TCR repertoire analysis as well as whole‐exome sequencing (WES) and transcriptome analysis. The TCR diversity index in EGFR‐mutant tumors was significantly higher than that in EGFR‐wild‐type tumors (median [range] 552 [162‐1,135] vs 230 [30‐764]; P < .01), suggesting higher T cell clonal expansion in EGFR‐wild‐type tumors than in EGFR‐mutant tumors. In WES, EGFR‐mutant tumors showed lower numbers of non‐synonymous mutations and predicted neoantigens than EGFR‐wild‐type tumors (P < .01, P = .03, respectively). The number of non‐synonymous mutations revealed a positive correlation with the sum of frequencies of the TCRβ clonotypes of 1% or higher in tumors (r = .52, P = .04). The present study demonstrates significant differences in TCR repertoires and the number of predicted neoantigens between EGFR‐mutant and wild‐type lung tumors. Our findings provide important information for understanding the molecular mechanism behind EGFR‐mutant patients showing unfavorable responses to immune checkpoint inhibitors.
Anthropometric measures and their association with risk factors for cardio-metabolic diseases in Kenyan adults

Abstract Background: The prevalence of cardio-metabolic diseases (CMD) is drastically increasing worldwide. Anthropometric measures of fat accumulation are correlated with CMD and Metabolic Syndrome (MS), but few studies have addressed this association in sub-Saharan African populations. Aim: To investigate the association between anthropometric features, MS and other CMD risk factors in a population from Kenya. Subjects and methods: In this cross-sectional study including 1405 Kenyans, anthropometric measurements including visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) were carried out. Fasting blood glucose and standard oral glucose tolerance test, fasting serum insulin and plasma lipids were analysed. Homeostatic model assessment of insulin resistance was calculated. Systolic and diastolic blood pressures were measured. Results: CMD risk factors and MS were associated with all anthropometric features, except for high-density lipoprotein cholesterol levels (p < 0.05). The strongest association between MS and anthropometrics was seen with SAT (β = 1.45 ± 0.32 in men and 0.88 ± 0.14 in women, both p < 0.05). Conclusions: Anthropometric measures, especially features of central obesity such as VAT and SAT, are relevant indicators of cardio-metabolic health in Kenyan populations. SAT is the strongest predictor of MS. These results highlight the need for further research on the pathological implication of VAT and SAT, in order to understand patterns of fat distribution and cardio-metabolic health among different ethnic groups.
The Negative Impact of Higher Body Mass Index on Sperm Quality and Erectile Function: A Cross-Sectional Study Among Chinese Males of Infertile Couples

The objective of the current study was to explore the role of body mass index (BMI) in sperm quality and erectile function in Chinese males of infertile couples. A total of 28 fertility centers in different regions of China were enrolled. Patient data were collected from June 1, 2017, through October 31, 2017. Semen analyses and demographic data were collected and the five-item International Index of Erectile Function (IIEF-5) questionnaire was used to evaluate the erectile function in participants with different BMIs. In total, 3,174 Chinese men of infertile couples with an average age of 33.11 ± 6.08 years were enrolled. The occurrence of obesity, overweight, normal weight, and underweight were 5.4%, 36.6%, 56.8%, and 1.2%, respectively. In addition to hypertension and diabetes, primary infertility, a longer course of infertility, and chronic prostatitis were risk factors for obesity. Compared with men of normal weight, adjusted odds ratios (ORs) for men with obesity, overweight, and underweight for semen volume <2 ml were 2.53 (95% CI [1.61, 3.97]), 1.33 (95% CI [1.09, 1.62]), and 0.84 (95% CI [0.29, 2.43]); for sperm progressive motility (A + B) (%) <32, the ORs were 1.60 (95% CI [1.16, 2.22]), 1.30 (95% CI [1.12, 1.51]), and 1.03 (95% CI [0.54, 1.98]); and for IIEF-5 ≤ 21, the ORs were 1.52 (95% CI [1.10, 2.10]), 1.11 (95% CI [0.96, 1.30]), and 0.62 (95% CI [0.31, 1.26]), respectively. Obesity was associated with lower semen volume, lower sperm motility, and erectile dysfunction in Chinese males of infertile couples.
Penile Circumferential Fascio- Cutaneous Onlay flap urethroplasty for Complex long Anterior Urethral Strictures. A Prospective Single centre experience with Five years follow up

Introduction: Long, complex strictures of the anterior urethra are a challenge and a variety of techniques to reconstruct complex anterior urethral strictures are presently available. Penile Circumferential fasciocutaneous flap urethroplasty is a useful technique for a long anterior urethral stricture due to the flap's hairless nature , mobility and ample length. Aims and Objectives: To assess the surgical outcomes of urethroplasty for a complex anterior urethral stricture, using a penile Circumferential fasciocutaneous Flap like postoperative complications, stricture free period. Material & Methods: Between 2007 to 2013, A total of 86 patients with long anterior urethral strictures of more than 5 cms in the age group of 20–65 yrs were subjected to circumferential penile skin urethroplasty . Results: The median intraoperative stricture length was 6.5 cms with median operating time of 100 minutes (90–145 min) and blood loss of 100 ml. All patients had five years of follow up. Year wise success rate was 92 % , 89 %, 84 %, 80 % & 79 %. 12.72% of the patients had recurrent strictures. Conclusion: Penile circular fasciocutaneous flap urethroplasty is a useful method for the reconstruction of a long anterior urethral stricture. A sufficient healthy margin should be acquired for better surgical results due to the fact that most recurrence occurs at the junction of the flap.
Circulatory microRNAs are not effective biomarkers of muscle size and function in middle-aged men.

Loss of muscle size and strength with aging is a major cause of morbidity. Although muscle size and strength are measured by imaging or fiber cross-sectional staining and exercise testing, respectively, the development of circulatory biomarkers for these phenotypes would greatly simplify identification of muscle function deficits. MicroRNAs (miRNAs) are short noncoding RNAs that regulate gene translation and, thereby, contribute to muscle phenotype. To assess circulatory miRNAs (c-miRNAs) applicability as potential biomarkers of muscular phenotypes, fasting plasma and muscle samples were obtained from 50 middle-aged healthy men [mean (SD); age: 48.8 yr (SD 4.5); BMI: 26.6 kg/m2 (SD 3.3)]. RT-PCR of 38 miRNAs with known regulatory function within skeletal muscle identified four c-miRNAs (miR-221, miR-451a, miR-361, and miR-146a) related to either total body lean mass, leg lean mass, and 50% thigh cross-sectional area (CSA), but not strength. There was no relationship with the expression of these miRNAs in muscle. Six miRNAs within muscle were correlated with whole body lean mass, leg lean mass, and isometric knee extension torque (miR-133a and miR-146a), and 50% thigh CSA (miR-486, miR-208b, miR-133b, and miR-208a). Only miR-23b demonstrated a relationship between tissue and circulatory expression; however, only 10% of the variance was explained. miR-146a in both plasma and muscle was related to phenotype; however, no relationship between plasma and muscle expression was evident. A different subset of miRNAs correlated to muscle phenotype in muscle compared with plasma samples, suggesting that c-miRNA biomarkers of muscle phenotype are likely unrelated to muscle expression in healthy individuals.
Interactions of the dynein-2 intermediate chain WDR34 with the light chains are required for ciliary retrograde protein trafficking

The dynein-2 complex drives retrograde ciliary protein trafficking by associating with the intraflagellar transport (IFT) machinery, containing IFT-A and IFT-B complexes. We recently showed that the dynein-2 complex, which comprises 11 subunits, can be divided into three subcomplexes: DYNC2H1–DYNC2LI1, WDR34–DYNLL1/DYNLL2–DYNLRB1/DYNLRB2, and WDR60–TCTEX1D2–DYNLT1/DYNLT3. In this study, we demonstrated that the WDR34 intermediate chain interacts with the two light chains, DYNLL1/DYNLL2 and DYNLRB1/DYNLRB2, via its distinct sites. Phenotypic analyses of WDR34-knockout cells exogenously expressing various WDR34 constructs showed that the interactions of the WDR34 intermediate chain with the light chains are crucial for ciliary retrograde protein trafficking. Furthermore, we found that expression of the WDR34 N-terminal construct encompassing the light chain–binding sites but lacking the WD40 repeat domain inhibits ciliary biogenesis and retrograde trafficking in a dominant-negative manner, probably by sequestering WDR60 or the light chains. Taken together with phenotypic differences of several WDR34-knockout cell lines, these results indicate that incorporation of DYNLL1/DYNLL2 and DYNLRB1/DYNLRB2 into the dynein-2 complex via interactions with the WDR34 intermediate chain is crucial for dynein-2 function in retrograde ciliary protein trafficking.
LRP5 in age-related changes in vascular and alveolar morphogenesis in the lung

Aging is associated with impaired angiogenesis and lung alveolar regeneration, which contributes to the increased susceptibility to chronic lung diseases (CLD). We have reported that the Wnt ligand co-receptor, low-density lipoprotein receptor-related protein 5 (LRP5), stimulates angiogenesis and lung alveolar regeneration. However, the role of LRP5 in age-related decline in vascular and alveolar morphogenesis remains unclear. In this report, we have demonstrated that vascular and alveolar structures are disrupted in the 24-month (24M) old mouse lungs. The expression of LRP5 and the major angiogenic factors, VEGFR2 and Tie2, is lower in endothelial cells (ECs) isolated from 24M old mouse lungs compared to those from 2M old mouse lungs. Vascular and alveolar formation is attenuated in the hydrogel implanted on the 24M old mouse lungs, while overexpression of LRP5, which restores angiogenic factor expression, reverses vascular and alveolar morphogenesis in the gel. Compensatory lung growth after unilateral pneumonectomy is inhibited in 24M old mice, which is reversed by overexpression of LRP5. These results suggest that LRP5 mediates age-related inhibition of angiogenesis and alveolar morphogenesis. Modulation of LRP5 may be a novel intervention to rejuvenate regenerative ability in aged lung and will lead to the development of efficient strategies for aging-associated CLD.