Miracle-dz/UniFAR-FTUs huggingface dataset:
Zika virus infection among symptomatic patients from two healthcare centers in Sao Paulo State, Brazil: prevalence, clinical characteristics, viral detection in body fluids and serodynamics

ABSTRACT Zika virus (ZIKV) clinical presentation and frequency/duration of shedding need further clarification. Symptomatic ZIKV-infected individuals identified in two hospitals in Sao Paulo State, Brazil, were investigated regarding clinical characteristics, shedding in body fluids, and serodynamics. Ninety-four of 235 symptomatic patients (Site A: 58%; Site B: 16%) had Real-Time PCR-confirmed ZIKV infection; fever, headache and gastrointestinal symptoms were less frequent, and rash was more frequent compared to ZIKV-negative patients. Real-Time PCR in serum had worse performance compared to plasma, while urine had the highest sensitivity. Shedding in genital fluids and saliva was rare. IgM positivity was the highest <14 days after the symptoms onset (86%), decreasing >28 days (24%); IgG positivity increased >14 days (96%) remaining positive in 94% of patients >28 days. ZIKV prevalence varied importantly in two neighboring cities during the same transmission season. Urine Real-Time PCR can improve diagnostic sensitivity; serum testing is less useful. Accurate serological tests are needed to improve diagnosis and surveillance.
Age and Perceived Employability as Moderators of Job Insecurity and Job Satisfaction: A Moderated Moderation Model

Workforce ageing and the need to work longer implies several challenges worldwide. Due to the potential for career prolongation, one such implication is to understand how age and perceived employability buffers relationship effects between job insecurity and job satisfaction. Therefore, this research aims to investigate the moderating roles of perceived employability and age on the relationship between job insecurity and job satisfaction. Hypotheses were tested using a three-way interaction model based on a cross-sectional design with a representative sample of 1,116 Chilean workers. Results show that age plays an important role in employees with high perceived employability; however, it has no effect on employees with low perceived employability. Younger workers with high perceived employability suffer less than do older employees with high perceived employability in terms of intrinsic job satisfaction. From a theoretical point of view, perceived employability in older workers does not reduce the unfavorable consequences of job insecurity. Regarding practical implications, organizations should manage and develop older workers by focusing on intrinsic aspects of their careers and on retirement preparation, as this will improve control and other positive resources in this population.
Validity of Self-reported Hypertension and Factors Related to Discordance Between Self-reported and Objectively Measured Hypertension: Evidence From a Cohort Study in Iran

Objectives Self-reporting can be used to determine the incidence and prevalence of hypertension (HTN). The present study was conducted to determine the validity of self-reported HTN and to identify factors affecting discordance between self-reported and objectively measured HTN in participants in the Ravansar Non-Communicable Diseases (RaNCD) cohort. Methods The RaNCD cohort included permanent residents of Ravansar, Iran aged 35-65 years. Self-reported data were collected before clinical examinations were conducted by well-trained staff members. The gold standard for HTN was anti-hypertensive medication use and blood pressure measurements. The sensitivity, specificity, positive and negative predictive values, and overall accuracy of self-reporting were calculated. Univariate and multivariate logistic regression were used to examine the discordance between self-reported HTN and the gold standard. Results Of the 10 065 participants in the RaNCD, 4755 (47.4%) were male. The prevalence of HTN was 16.8% based on self-reporting and 15.7% based on medical history and HTN measurements. Of the participants with HTN, 297 (18.8%) had no knowledge of their disease, and 313 (19.9%) had not properly controlled their HTN despite receiving treatment. The sensitivity, specificity, and kappa for self-reported HTN were 75.5%, 96.4%, and 73.4%, respectively. False positives became more likely with age, body mass index (BMI), low socioeconomic status, and female sex, whereas false negatives became more likely with age, BMI, high socioeconomic status, smoking, and urban residency. Conclusions The sensitivity and specificity of self-reported HTN were acceptable, suggesting that this method can be used for public health initiatives in the absence of countrywide HTN control and detection programs.
The Clinical Efficacy of a Pure Alginate Formulation (Lamina G) for Controlling Symptoms in Individuals with Reflux Symptoms: A Randomized Clinical Study

Background/Aims Bicarbonate-containing alginate formulations are reported to be effective for controlling reflux symptoms. However, the efficacy of Lamina G alginate without gas production has not been reported. The aim is to evaluate the efficacy of a non-bicarbonate alginate in individuals with reflux symptoms without reflux esophagitis. Methods Participants who had experienced heartburn or regurgitation for 7 consecutive days were randomized to one of the following treatment groups: proton pump inhibitors (PPI) plus alginate (combination) or PPI plus placebo (PPI only). In addition, as a reference group, patients received placebo plus alginate (alginate only). The primary endpoint compared the percentage of patients with complete resolution of symptoms for the final 7 days of the treatment. Secondary endpoints compared changes in symptom score, symptom-free days during the treatment period, the Reflux Disease Questionnaire, Patient Assessment of Upper Gastrointestinal Disorders (PAGI)-Quality of Life and PAGI-Symptoms Severity Index scores, the investigator’s assessment of symptoms, and incidence of adverse events. Results Complete resolution of heartburn or regurgitation was not significantly different between the combination and PPI only groups (58.7% vs 57.5%, p=0.903). The secondary endpoints were not significantly different between the two groups. Complete resolution of heartburn or regurgitation, did not differ between the alginate only reference group and the PPI only group (75.0% vs 57.5%, p=0.146). Conclusions The addition of non-bicarbonate alginate to PPI was no more effective than PPI alone in controlling reflux symptoms.
Application of a Strontium-Loaded, Phase-Transited Lysozyme Coating to a Titanium Surface to Enhance Osteogenesis and Osteoimmunomodulation

Background To fabricate strontium (Sr)-incorporated titanium (Ti) surfaces by a novel 1-step phase-transited lysozyme (PTL) treatment, and investigate the effects of the prepared samples on osteogenesis and osteoimmunoregulation. Material/Methods Five groups of titanium specimens were prepared, including Ti, PTL, PTL@10Sr (PTL coating with 10 mg/mL Sr), PTL@20Sr PTL coating with 20 mg/mL Sr), and PTL@50Sr (PTL coating with 50 mg/mL Sr) groups. Behaviors of bone marrow mesenchymal stem cells (BMSCs) such as initial attachment, spread, proliferation, and migration, on different surfaces were examined by immunofluorescence, MTS assay, and Transwell system. Then the osteogenic differentiation of BMSCs was detected. When an immune response was factored in, the polarization of macrophages induced by the prepared surfaces was detected by real-time PCR, and the response of BMSCs to macrophage-conditioned medium was assessed in terms of cell migration and osteogenic differentiation. Finally, an in vivo study was performed, using the rat femora implant model, to evaluate the potential for osteogenic induction and osteoimmunoregulation of materials. Results Our in vitro experiments indicated that PTL coating could improve cell spread and adhesion, and the stable Sr release of PTL@Sr layers could promote cell migration and osteogenesis. Moreover, PTL@Sr surface could regulate the immune response of macrophages resulting in enhanced BMSCs recruitment and osteogenic differentiation. The in vivo evaluation showed less inflammatory infiltration and improved bone formation in the PTL@20Sr group. Conclusions The Sr-loaded PTL layers have greater potential for the induction of osteogenic differentiation of BMSCs, meanwhile Sr-loaded PTL layers could adjust the immune response and thus promote osteogenesis both in vitro and in vivo.
Diagnostic delay of pediatric inflammatory bowel disease in Saudi Arabia

Background/Aim: Delay in the diagnosis of inflammatory bowel disease (IBD) is associated with complications. Our aim was to describe the pattern and risk factors associated with delay in the diagnosis of IBD in Saudi children. Patients and Methods: This was a multicenter study with a retrospective/prospective design. Data on diagnostic delay in children with Crohn's disease (CD) and ulcerative colitis (UC) were retrieved from physician's notes. Multivariate regression analysis was used to assess the risk factors associated with long delay in diagnosis. Results: There were 240 and 183 Saudi children with CD and UC, respectively. The median delays in diagnosis were 8 and 5 months in CD and UC, respectively, significantly longer in children with CD than UC (P < 0.001). Long diagnostic delays (>75th percentile) were 24 and 8.8 months for CD and UC, respectively. Ileal location was a significant risk factor in CD and the age of onset above 10 years was protective in UC. Conclusions: Long diagnostic delay in IBD was mainly due to the longer delay in gastroenterologist consultation. Review of the referral system is needed to focus on measures to reduce long delays in diagnosis. The ileal location as a risk factor in CD and age older than 10 years as protective in UC should help recognition and early referral.
Different Clinical Presentations and Management in Complete Androgen Insensitivity Syndrome (CAIS)

Complete androgen insensitivity syndrome (CAIS) is an X-linked recessive genetic disorder resulting from maternally inherited or de novo mutations involving the androgen receptor gene, situated in the Xq11-q12 region. The diagnosis is based on the presence of female external genitalia in a 46, XY human individual, with normally developed but undescended testes and complete unresponsiveness of target tissues to androgens. Subsequently, pelvic ultrasound or magnetic resonance imaging (MRI) could be helpful in confirming the absence of Mullerian structures, revealing the presence of a blind-ending vagina and identifying testes. CAIS management still represents a unique challenge throughout childhood and adolescence, particularly regarding timing of gonadectomy, type of hormonal therapy, and psychological concerns. Indeed this condition is associated with an increased risk of testicular germ cell tumour (TGCT), although TGCT results less frequently than in other disorders of sex development (DSD). Furthermore, the majority of detected tumoral lesions are non-invasive and with a low probability of progression into aggressive forms. Therefore, histological, epidemiological, and prognostic features of testicular cancer in CAIS allow postponing of the gonadectomy until after pubertal age in order to guarantee the initial spontaneous pubertal development and avoid the necessity of hormonal replacement therapy (HRT) induction. However, HRT is necessary after gonadectomy in order to prevent symptoms of hypoestrogenism and to maintain secondary sexual features. This article presents differential clinical presentations and management in patients with CAIS to emphasize the continued importance of standardizing the clinical and surgical approach to this disorder.
Self‐assembling peptide modified with QHREDGS as a novel delivery system for mesenchymal stem cell transplantation after myocardial infarction

The lower cell survival and retention in the hostile microenvironment after transplantation has been implicated as a major bottleneck in the advancement of stem cell therapy for myocardial infarction (MI). In this study, we designed a novel self‐assembling peptide (SAP) by attaching prosurvival peptide QHREDGS derived from angiopoeitin‐1 to the known SAP, RADA16‐I. The mesenchymal stem cells (MSCs) were harvested from male rats and cytoprotective effect of this designer SAP (DSAP) on cultured MSCs was detected by Hoechst 33342 staining after being exposed to oxygen and glucose deprivation (OGD). The cytoprotective effect of MSCs seeded in DSAP (DSAP‐MSCs) on OGD treated cardiomyocytes was examined by TUNEL staining, phosphorylated (p‐) protein kinase B (Akt) level, and ELISA. The therapeutic potential of MSC transplantation carried in DSAP was evaluated in a female rat MI model. PBS, MSCs alone, MSCs seeded in SAP (SAP‐MSCs), or DSAP‐MSCs were transplanted into the border of the infarcted area, respectively. DSAP not only increased the proliferation of MSCs and decreased apoptosis of MSCs after OGD treatment but also promoted the secretion of IGF‐1 and HGF in MSCs. Treatment with culture supernatant of DSAP‐MSCs markedly reduced the percentage of apoptotic cardiomyocytes and increased the level of p‐Akt. Compared with the MSC group and SAP‐MSC group, DSAP‐MSC injection improved cardiac function and reduced infarct size, collagen content, and cell apoptosis. The number of Y chromosome–positive cells and microvessels in the DSAP‐MSC group was higher than those in the MSC group and SAP‐MSC group. Moreover, DSAP‐MSC transplantation down‐regulated the expression of IL‐6 and IL‐1β and up‐regulated the level of VEGF and HGF. Interestingly, miR‐21 was enriched in DSAP‐MSC‐derived exosomes (DSAP‐MSC‐Exos) and the protection against cardiomyocyte apoptosis by DSAP‐MSC‐Exos was inhibited when miR‐21 was knocked down. Furthermore, miR‐21 contributed to the improvement of cardiac function after DSAP‐MSC‐Exo injection in a rat model of MI. Additionally, the combination of DSAP and cardiotrophin‐1 (Ctf1) pretreatment further improved the survival of MSCs and the efficiency of MSC transplantation. We proposed QHREDGS‐modified SAP as an effective cell delivery system and demonstrated that MSC transplantation in this DSAP promoted angiogenesis and paracrine, thereby reducing scar size and cell apoptosis as well as improving cardiac function probably via exosome‐mediated miR‐21 after MI. Furthermore, for the first time, we proposed that DSAP, especially working together with Ctf1 pretreatment, could be a valuable way to improve the survival of MSCs and the efficiency of MSC transplantation after MI. —Cai, H. , Wu, F. ‐Y. , Wang, Q. ‐L. , Xu, P., Mou, F. ‐F. , Shao, S. ‐J., Luo, Z. ‐R. , Zhu, J., Xuan, S. ‐S. , Lu, R. , Guo, H. ‐D. Self‐assembling peptide modified with QHREDGS as a novel delivery system for mesenchymal stem cell transplantation after myocardial infarction. FASEB J. 33, 8306–8320 (2019). www.fasebj. org
Tumor growth suppression using a combination of taxol-based therapy and GSK3 inhibition in non-small cell lung cancer

Glycogen synthase kinase-3 (GSK3) is over-expressed and hyperactivated in non-small cell lung carcinoma (NSCLC) and plays a role in ensuring the correct alignment of chromosomes on the metaphase plate during mitosis through regulation of microtubule stability. This makes the enzyme an attractive target for cancer therapy. We examined the effects of a selective cell-permeant GSK3 inhibitor (CHIR99021), used alone or in combination with paclitaxel, using an in vitro cell growth assay, a quantitative chromosome alignment assay, and a tumor xenograft model. CHIR99021 inhibits the growth of human H1975 and H1299 NSCLC cell lines in a synergistic manner with paclitaxel. CHIR99021 and paclitaxel promoted a synergistic defect in chromosomal alignment when compared to each compound administered as monotherapy. Furthermore, we corroborated our in vitro findings in a mouse tumor xenograft model. Our results demonstrate that a GSK3 inhibitor and paclitaxel act synergistically to inhibit the growth of NSCLC cells in vitro and in vivo via a mechanism that may involve converging modes of action on microtubule spindle stability and thus chromosomal alignment during metaphase. Our findings provide novel support for the use of the GSK3 inhibitor, CHIR99021, alongside taxol-based chemotherapy in the treatment of human lung cancer.
Roles of citric acid in conjunction with saline nebulization in experimental tracheostomy in guinea pigs

Abstract Purpose: Tracheostomy usually accompanied by the impairment of cough reflex, which may affect the clearance of secretions and result in the occurrence and development of pulmonary inflammation. Previous research has demonstrated that citric acid could effectively evoke cough. However, there are limited data available on this topic specific to the cough stimulation method, and the roles of citric acid in tracheostomy still remain obscure. The aims of present study were to identify the potential roles of citric acid in conjunction with saline nebulization in tracheostomy in guinea pigs. Materials and Methods: Experimental tracheostomy model was induced in guinea pigs, and different nebulization interventions were implemented. The expression of P-selectin and platelet count were analyzed by flow cytometer and automatic globulimeter, the histological changes in trachea and lung tissue were assessed by hematoxylin and eosin staining, and the inflammatory cytokines and substance P (SP) levels in bronchoalveolar lavage fluid were evaluated by enzyme-linked immunosorbent assay. Results: Tracheostomy resulted in the disorder of trachea mucosa and cilia, the inflammatory cell infiltration in lung tissue, the increase of IL-6, TNF-α levels and the decrease of SP level. Citric acid alone increase the SP level, and the joint action of citric acid and saline nebulization further showed significantly beneficial effects on pathological, inflammatory changes and SP level. Conclusions: Citric acid combined with saline nebulization contributes to the alleviation of tracheotomy-induced tracheal damage and pulmonary inflammation in an experimental tracheostomy model in guinea pigs. This may provide novel insights into the inflammation management and cough recovery after tracheostomy.
Conserved 2nd Residue of Helix 8 of GPCR May Confer the Subclass-Characteristic and Distinct Roles through a Rapid Initial Interaction with Specific G Proteins

To obtain a systematic view of the helix-8-second residue responsible for G protein-coupled receptor (GPCR)–G protein initial specific interactions, 786 human GPCRs were subclassified based on the pairs of agonist groups and target G proteins and compared with their conserved second residue of helix 8. Of 314 non-olfactory and deorphanized GPCRs, 273 (87%) conserved single amino acids in the subclasses, while 93 (58%) of the 160 subclasses possessed only a single GPCR member. Class B, C, Frizzled, and trace amine-associated GPCRs demonstrated 100% conservation, whereas class I and II olfactory and vomeronasal 1 receptors demonstrated much lower rates of conservation (20–47%). These conserved residues are characteristic of GPCR classes and G protein subtypes and confer their functionally-distinct roles.
Renal tubular P-glycoprotein expression is reduced in plasma cell disorders

Background P-glycoprotein (P-gp) transports many chemicals that vary greatly in their structure and function. It is normally expressed in renal proximal tubular cells. We hypothesized that P-gp expression influences light chain excretion. Therefore, we investigated whether renal tubular P-gp expression is altered in patients with plasma cell disorders. Methods We evaluated renal biopsy specimens from patients with plasma cell disorders (n = 16) and primary focal segmental glomerulosclerosis (the control group, n = 17). Biopsies were stained with an anti-P-gp antibody. Loss of P-gp expression was determined semi-quantitatively. Groups were compared for loss of P-gp expression, and clinical variables. Results P-gp expression loss was more severe in patients with plasma cell disorders than it was in those with glomerulonephritis (P = 0.021). In contrast, clinical and histological parameters including serum creatinine, level of urinary protein excretion, and interstitial fibrosis/tubular atrophy grade were not significantly different between the groups. P-gp expression loss increased with age in patients with plasma cell disorders (P = 0.071). This expression loss was not associated with serum creatinine, the level of urinary protein excretion or the interstitial fibrosis/tubular atrophy grade. There was no significant association between the severity of P-gp expression loss with the types and serum levels of light chains, isotypes and serum immunoglobulin levels. Conclusion Renal tubular P-gp expression is significantly down-regulated in patients with plasma cell disorders characterized by nephrotic range proteinuria. Additional studies are needed to determine whether reintroduction of renal tubular P-gp expression would mitigate the proximal tubular injury that is caused by free-light chains.
Microplastics in coastal areas and seafood: implications for food safety

ABSTRACT Microplastics have become ubiquitous in the marine environment. Microplastics have been detected in many coastal environments and species, including commercial seafood. This triggers concern about potential economic impacts and the risks of dietary exposure, especially for coastal communities. However, data regarding the levels of microplastics in coastal seafood and their toxicological effects are still limited. Accordingly, the dietary risk is still poorly explored. This review summarizes and discusses recent scientific findings on (i) the presence of microplastics in coastal waters, (ii) the occurrence of microplastics in coastal seafood and the likelihood of trophic transfer, and (iii) the effects of microplastics on coastal fish and shellfish species. Human toxicity data are also reviewed, but the risks for human health are difficult to determine due to limited data. Based on available worldwide data, the estimation of microplastics intake through seafood consumption shows a huge variation. Additionally, a lack of standardized analytical methods complicates the comparison of results between studies and therefore seriously affects the reliability of risk assessments. It is concluded that more exposure and toxicity data are needed properly to assess human health risks of microplastics in coastal seafood, and the lack of data currently impede the derivation of a risk-based food safety standard. The pros and cons of an interim solution, i.e. setting a provisional action level, are being discussed.