bluuebunny/crossref_metadata_2025 huggingface dataset:
Engagement of private healthcare providers for case finding of Tuberculosis and Diabetes Mellitus in Pakistan
Authors: Habib Shifa Salman , Rafiq Sana , Jamal Wafa Zehra , Ayub Shaikh Mohammad , Ferrand Rashida Abbas , Khan Aamir , Zaidi Syed Mohammad Asad
Published: April 2020

Background: The rising co-epidemic of tuberculosis (TB) and diabetes mellitus (DM) is a challenge for constrained health systems in low and middle-income countries. Diabetes is a known risk factor for tuberculosis and associated with poor tuberculosis treatment outcomes, while tuberculosis is associated with worsening glycemic control. We investigated the performance of bi-directional TB and DM case finding approaches through a private-sector engagement model in Karachi, Pakistan. Methods: Between July 2016 and July 2018, private health care providers were engaged to generate referrals for bi-directional TB and DM screening at private diagnostic and treatment centers in Karachi, Pakistan. Individuals diagnosed with TB underwent glycated hemoglobin (HbA1c) testing at the time of anti-tuberculous treatment initiation and at three -month follow up stage. All individuals with a history of diabetes or random blood sugar of greater than 200 mg/dl were screened for TB using a chest X-ray and Xpert MTB/RIF. Results: A total of 6,312 persons with tuberculosis were tested on HbA1c at treatment initiation, of whom 1,516 (24%) were newly diagnosed with DM. About one third of those with HbA1c in the diabetic range (≥ 6.5%) at baseline were found to have a normal HbA1c (<5.7%) result at 3-month follow-up. A total of 3,824 individuals with DM, of whom 2,396 (63%) were known cases and 1,428 (37%) were newly identified with random blood sugar >200mg/dl, underwent chest x-ray and Xpert MTB/RIF testing, with 321 (13.4%) known and 54 (3.8%) new diabetics respectively identified with tuberculosis. Conclusion: This study demonstrates a high yield of TB and DM through bidirectional screening and the feasibility of engagement of private sector in finding missing cases of tuberculosis and diabetes. Given the high prevalence of undiagnosed DM in individuals with TB tuberculosis patients, there is a need to scale-up DM screening within TB programmes. Increased awareness of the high risk of TB among individuals with DM is needed among private health providers and screening for TB among diabetics should be strongly considered.
The burden and outcomes of stroke in young adults at a tertiary hospital in Tanzania: A comparison with older adults
Authors: Matuja Sarah Shali , Munseri Patricia , Khanbhai Khuzeima
Published: April 2020

Background: Stroke burden in young adults is growing associated with unique risk factors and devastating outcomes. We aimed to investigate the magnitude, risk factors and outcomes of first ever stroke in young adults ≤45 years compared to older adults >45 years.Methods: All patients with a World Health Organization clinical definition of stroke at a tertiary hospital in Tanzania were enrolled. The National Institute of Health Stroke Scale and Modified Rankin Scale were used to assess admission stroke severity and outcomes respectively. Kaplan-Meier analysis was used to describe survival and Cox-proportional hazards model was used to examine predictors of fatality.Results: We enrolled 369 first ever stroke participants over 8 months. First strokes accounted for one quarter of medical admissions in both younger and older groups, 123/484 {(25.4%) [95% CI 21.5% - 29.3%]} and 246/919 {(26.8%) [95% CI 23.9% - 29.6%]} respectively. Hemorrhagic stroke occurred in 47 (42.3%) vs 62 (27.2%) for the young and old respectively p=0.005. Factors associated with stroke in the young were: a new diagnosis of hypertension in 33 (26.8%) vs 23 (9.3%) p<0.001, HIV infection 12 (9.8%) vs 7 (2.8%) p=0.005, use of hormonal contraception in females 33 (48.5%) vs 13 (9.4%) p<0.001, elevated serum low density lipoproteins 28 (27.7%) vs 29 (16.4%) p=0.024, hypercholesteremia 34 (31.2%) vs 40 (20.2%), p=0.031, sickle cell disease 11 (9.7%) vs 9 (4.2%) p=0.047 and thrombocytosis 12 (16.9%) vs 8 (5.6%) p=0.007. The overall 30-day fatality rate was 215 (61.3%); 57 (49.1%) vs 158 (67.2%) in the young and old respectively. Independent predictors of fatality were: severe stroke {HR 10.35 (95% CI: 1.397–76.613)}, leukocytosis {HR 2.23 (95% CI: 1.448–3.419)} and fever {HR 1.79 (95% CI: 1.150–2.776)}.Conclusions: There is a high burden of stroke in young adults that is coupled with a high 30-day fatality rate. Screening and management of hypertension is crucial in the prevention of stroke. More research is needed to identify factors which cause death, allowing the development of sustainable interventions to reduce early post stroke fatality in this group.
FDNC5/Irisin improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells for myocardial infarction
Authors: Deng Jingyu , Zhang Ning , Wang Yong , Yang Chao , Xin Chao , Zhao Jinming , Jin Zhitao , Cao Feng , Zhang Zheng
Published: April 2020

Background: The beneficial functions of bone marrow mesenchymal stem cells (BM-MSCs) decline with decreased cells survival, limiting their therapeutic efficacy for myocardial infarction (MI). Irisin, a novel myokine which is cleaved from its precursor fibronectin type III domain-containing protein 5 (FNDC5), is believed involved in a cardioprotective effect but little was known on injured BM-MSCs and MI repair yet. Here, we investigated whether FNDC5 or irisin could improve the low viability of transplanted BM-MSCs and increase their therapeutic efficacy after MI. Methods: BM-MSCs, isolated from dual-reporter firefly luciferase and enhanced green fluorescent protein positive (Fluc+– eGFP+) transgenic mice, were exposed to normoxic condition and hypoxic stress for 12 h, 24 h, and 48 h, respectively. In addition, BM-MSCs were treated with irisin (20 nmol/L) and FNDC5-OV in serum deprivation (H/SD) injury. Furthermore, BM-MSCs were engrafted into infarcted hearts with or without FNDC5-OV. Results: Hypoxic stress contributed to increased apoptosis, decreased cells viability and paracrine effects of BM-MSCs while irisin or FNDC5-OV alleviated these injuries. Longitudinal in vivo bioluminescence imaging illustrated that FNDC5-MSCs treatment improved the survival of transplanted BM-MSCs, which ameliorated the increased apoptosis and decreased angiogenesis of BM-MSCs in vivo. Furthermore, FNDC5-MSCs therapy significantly reduced fibrosis and alleviated injured heart function. Conclusions: The present study indicated that irisin or FNDC5 improved BM-MSCs engraftment and paracrine effects in infarcted hearts, which might provide a potential therapeutic target for MI.
Proximal and distal predictors of self-regulatory change in children aged 4 to 7 years
Authors: Williams Kate E , Howard Steven J.
Published: April 2020

Background Growth in early self-regulation skills has been linked to positive health, wellbeing, and achievement trajectories across the lifespan. While individual studies have documented specific influences on self-regulation competencies in early childhood, few have modelled a comprehensive range of predictors of self-regulation change across health, development, and environment simultaneously. This study aimed to examine the concurrent associations among a range of proximal and distal influences on change in children’s self-regulation skills over 2 years from age 4-5 years. Methods Data from the Longitudinal Study of Australian Children (N= 4983) were used in a structural equation model, predicting a multi-source composite measure of self-regulation at each of 4-5 years and 6-7 years. By controlling for earlier self-regulation and covariates, the model examined the relative contributions of a comprehensive range of variables to self-regulation change including health, development, educational, home environment, time-use, and neighbourhood characteristics. Results The significant predictors of children’s self-regulation growth across 4 to 7 years were fewer behavioural sleep problems, higher gross motor and pre-academic skills, lower levels of maternal and paternal angry parenting, and lower levels of financial hardship. There were also marginal effects for high-quality home learning environments and child-educator relationships. Conclusion Findings suggest that if we are to successfully foster children’s self-regulation skills, interventionists would do well to operate not only on children’s current capacities but also key aspects of their surrounding context.
Lumbar plain radiograph is not reliable to identify lumbosacral transitional vertebra types according to Castellvi classification principle
Authors: Hou Lisheng , Bai Xuedong , Li Haifeng , Gao Tianjun , Li Wei , Wen Tianyong , He Qing , Ruan Dike , Shi Lijing , Bing Wei
Published: April 2020

Background: The anteroposterior view of the lumbar plain radiograph (AP-LPR) was chosen as the original and first radiographic tool to determine and classify lumbosacral transitional vertebra with morphological abnormality (MA-LSTV) according to the Castellvi classification. However, recent studies found that AP-LPR might not be sufficient to detect or classify MA-LSTV correctly. The present study aims to verify the reliability of AP-LPR on detecting and classifying MA-LSTV types, taking coronal reconstructed CT images (CT-CRIs) as the gold criteria. Methods: Patients with suspected MA-LSTVs determined by AP-LPR were initially enrolled. Among them, those who received CT-CRIs were formally enrolled to verify the sensitivity of AP-LPR on detecting and classifying MA-LSTV types according to the Castellvi classification principle. Results: A total of 298 cases were initially enrolled as suspected MA-LSTV, among which 91 cases who received CT-CRIs were enrolled into the final study group. All suspected MA-LSTVs were verified to be real MA-LSTVs by CT-CRIs. However, 35.2% of the suspected MA-LSTV types judged by AP-LPR were not consistent with the final types judged by CT-CRIs. Two suspected type IIIa and 20 suspected type IIIb MA-LSTVs were verified to be true, while 9 of 39 suspected type IIa, 9 and 3 of 17 suspected type IIb, and 11 of 13 suspected type IV MA-LSTVs were verified to truly be type IIIa, IIIb, IV and IIIb MA-LSTVs by CT-CRIs, respectively. Incomplete joint-like structure (JLS) or bony union structure (BUS) and remnants of sclerotic band (RSB) between the transverse process (TP) and sacrum were considered to be the main reasons for misclassification.Conclusion: Although AP-LPR could correctly detect MA-LSTV, it could not give accurate type classification. CT-CRIs could provide detailed information between the TP and sacrum area and could be taken as the gold standard to detect and classify MA-LSTV.
A prospective observational study on critically ill children with diaphragmatic dysfunction: clinical outcomes and risk factors
Authors: Xue Yang , Yang Chun-Feng , Ao Yu , Qi Ji , Jia Fei-Yong
Published: April 2020

Background Diaphragmatic dysfunction (DD) has a great negative impact on clinical outcomes, and it is a well-recognized complication in adult patients with critical illness. However, DD is largely unexplored in the critically ill pediatric population. The aim of this study was to identify risk factors associated with DD, and to investigate the effects of DD on clinical outcomes among critically ill children. Methods Diaphragmatic function was assessed by diaphragm ultrasound. According to the result of diaphragmatic ultrasound, all enrolled subjects were categorized into the DD group (n=24) and the non-DD group (n=46). Collection of sample characteristics in both groups include age, sex, height, weight, primary diagnosis, complications, laboratory findings, medications, ventilatory time and clinical outcomes. Results The incidence of DD in this PICU was 34.3%. The level of CRP at discharge (P=0.003) in the DD group was higher than the non-DD group, and duration of elevated C-reactive protein (CRP) (P<0.001), sedative days (P=0.008) and ventilatory treatment time (P<0.001) in the DD group was significantly longer than the non-DD group. Ventilatory treatment time and duration of elevated CRP were independently risk factors associated with DD. Patients in the DD group had longer PICU length of stay, higher rate of weaning or extubation failure and higher mortality. Conclusion DD is associated with poorer clinical outcomes in critically ill childern, which include a longer PICU length of stay, higher rate of weaning or extubation failure and a higher mortality. The ventilatory treatment time and duration of elevated CRP are main risk factors of DD in critically ill children.
Impairment of maturation of BMP-6 (35kDa) correlates with delayed fracture healing in experimental diabetes
Authors: Guo Qi-Dong , Wang Wei-Jie , Abboud Rami , Guo Zheng
Published: April 2020

Background: Although it is known that diabetes interferes with fracture healing, the mechanisms remain poorly understood. The aim of this study was to investigate the correlation of BMP-6 and BMP-9 with the impairment in fracture healing in diabetes, by analyses of the difference in size and calcification of the callus, mechanical endurance and expressing BMP-6 and BMP-9 in the callus, using a clinical related diabetic rodent model. Methods: We evaluated femur fracture healing by quantification of size and calcification of the callus by X-ray, histological and histochemical images, loading capacity of the fractured bone and amount of BMP-6 in the callus and the bones using Western blot assay. Results: Significant upregulation of BMP-6 in the callus and the fractured bones of both non-diabetic and the diabetic animals was observed, at the end of the 2nd and the 4th weeks after fracture. However, significantly lower levels of BMP-6 at 35kDa with smaller sizes of calcified callus and poor loading capacity of the healing bones were detected in the diabetic animals, compared to the non-diabetic controls. The impairment of the maturation procedure of BMP-6 (35 kDa) from precursors may be underlying the downregulation of the BMP-6 in diabetic animals. Conclusions: It could be concluded that the delayed fracture healing in the diabetic animals is correlated with deficiency of BMP-6 (35 kDa), which may be caused by impairment of maturation procedure of BMP-6 from precursors to functioning format. This is a primary study but an important step to explore the molecular pathogenesis of impairment of fracture healing in diabetes and to molecular therapeutic approach for the impairment of fracture healing.
Constitutively Active Androgen Receptor Supports the Metastatic Phenotype of Endocrine-Resistant Hormone Receptor-Positive Breast Cancer
Authors: Bahnassy Shaymaa , Bawa-Khalfe Tasneem , Thangavel Hariprasad , Quttina Maram , Khan Ashfia , Dhanyalayam Dhanya , Ritho Joan , Karami Samaneh , Ren Jing
Published: April 2020

Background: Hormone receptor positive (HR+) breast cancer (BCa) is the most frequently diagnosed subtype. Acquired and intrinsic resistance to conventional endocrine therapy (ET) commonly occurs and prompts incurable metastatic disease. Hence, ET-resistant (ET-R) HR+ BCa presents a therapeutic challenge. Previous studies show elevated androgen receptor (AR) that supports resistance to ET tamoxifen and correlates with HR+ BCa metastasis. Yet surprisingly, studies with AR-blocker enzalutamide (Enz) in ET-R HR+ BCa present conflicting results. We now report that a constitutively active, unique from canonical Enz-targeted, AR accumulates in endocrine resistant HR+ BCa cells. Methods: AR protein profiles in acquired and intrinsic ET-R HR+-BCa were defined with cell-free modification tests, in-house in-vivo SUMOylation assays, and PLA imaging. Genomic activity of native AR and modified-AR mimetic was tested with reporter assays and limited transcriptome analysis. Spheroid growth and migration studies were used to evaluate inhibitory actions of Enz and combinatorial therapy. Results: Sustained higher molecular weight SUMO-modified AR (SUMO-AR) persists in acquired and intrinsic ET-R BCa cell lines. Concurrently, SUMO isoforms and global SUMO-modified proteome also accumulates in the same cell lines. We identified AR as a novel substrate for the SUMO-E3 ligase HSPB1/Hsp27. Independent of ligand, SUMO-AR is resilient to ubiquitin-mediated proteasomal degradation, enriched in the nucleus, readily chromatin-bound, and transcriptionally active. Constitutive SUMO-AR initiates a gene-expression profile that favors epithelial-mesenchymal transition. Enz combined with a SUMO inhibitor attenuates migration and metastatic phenotype of ET-R HR+ BCa. Conclusion: Targeting both unmodified and SUMO-modified AR prevents the metastatic progression of HR+ BCa with ET-R.
Understanding the Social Construction of Health by Incorporating Biomarker in the Contemporary China
Authors: xie donghong , Wang Jiwen
Published: April 2020

Background: Researchers interested in the effect of health on various life outcomes often use self-reported health and disease as an indicator of true, underlying health status. However, the validity of reporting is questionable as it relies on the awareness, recall bias and social desirability. Accordingly, the measured biomarker is generally regarded as a more precise indication of the disease. Objectives: The study aimed to examine the discrepancy between the reporting and biomarkers of hypertension and diabetes in the contemporary China, and explore sociodemographic characteristics that are correlated with misreporting. Methods: Using data from the third wave of China Health and Retirement Longitudinal Study (CHARLS), we selected individuals aged 40-85 years old who participated in both a health interview survey and a biomarker examination. Sensitivity, specificity, false negative reporting and false positive reporting were used as measurements of (dis)agreements or (in)validity. Binary and multinomial logistic regression were used to estimate under-report or over-report of hypertension and diabetes. Results: Self-reported hypertension and diabetes showed low sensitivity (71.98% and 49.21%, respectively) but high specificity (93.71% and 98.05%, respectively). False positive reporting of hypertension and diabetes were 3.85% and 1.67%, while false negative reports were extremely high at 10.85% and 7.38%. Education degree, hukou, age and gender affected both the specific error and the overall error of reporting hypertension and diabetes, but there were some differences in the magnitude and direction. Conclusion: Self-reported conditions underestimate the disease burden of hypertension and diabetes. Adding objective measurements into social survey could improve data accuracy allowing better understanding of socioeconomic inequalities in health, especially collecting biological indicators for populations with limited access to regular healthcare in China. Furthermore, there is an urgent need to provide basic health education and physical examination to citizens, to facilitate access to healthcare and make focused interventions to lower the incidence and unawareness of disease in China.
Longitudinal prospective evaluation of oral health-related quality of life in young patients undergoing fixed orthodontic appliance treatment
Authors: Elhussein Mustafa , Benson Philip
Published: April 2020

Background: The objectives of this study were to investigate relationships between change in the aesthetic appearance before and after orthodontic treatment and patient-reported change in oral health-related quality of life (OHRQoL), and to assess the responsiveness of two OHRQoL measures to any changes from orthodontic treatment.Methods: Two hundred and one participants in a randomized clinical trial, involving two teaching hospitals and four specialist practices, were administered one of two age-specific questionnaires, either the Child Perceptions Questionnaire (CPQ11-14-ISF-16) or the Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ), before and after orthodontic treatment. Clinical photographs were assessed by two groups of laypeople and orthodontists using the Index of Orthodontic Treatment Need Aesthetic Component (IOTN-AC).Results: There was a mean reduction in the total CPQ11-14-ISF-16 scores of 3.9 (SD=8.0), and a mean reduction of 34.2 (SD=18.5) in the total PIDAQ score. CPQ11-14-ISF-16 demonstrated poor longitudinal construct validity (p=0.155). Correlations between the change in total CPQ11-14-ISF-16 scores and change in IOTN-AC assessments was small for both orthodontists (r=-0.084; p=0.516) and laypeople (r=-0.140; p=0.225). There were higher associations between the improvement in the Social well-being (SWB) subdomain and improvement in IOTN-AC. Correlations between the changes in total PIDAQ scores and the IOTN-AC assessments, were higher in comparison to the correlations with CPQ11-14 (orthodontists; r=0.223, laypeople; r=0.025).Conclusion: CPQ11-14-ISF-16 and IOTN-AC measure different attributes. This demonstrated the role of SWB on children OHRQoL. Condition-specific measures (PIDAQ) are more responsive to change in self-reported OHRQoL than generic measures (CPQ11-14-ISF-16) after treatment.
Rabies virus phosphoprotein P5 binding to BECN1 regulates self-replication by CASP2-mediated autophagy signaling pathway
Authors: Liu Juan , Liao Min , Yan Yan , Wang Hailong , Yang Hui , Zhou Jiyong
Published: April 2020

Background
Rabies virus (RABV) is reported to encode five phosphoproteins (P), which are involved in viral genomic replication, axonal transport, oxidative stress, interferon antagonism, and autophagy induction. However, the functions of the different P proteins are poorly understood.
Methods
Immunofluorescence staining and western blot were performed to detect the autophagy activity, the form of ring-like structure, and the colocalization of BECN1 and P. Coimmunoprecipitation was performed to detect the interaction between P and BECN1. QRT-PCR and TCID50 assay were performed to detect the replication level of RABV. Small interfering RNA was used to detect the autophagy signaling pathway.
Results
We found that P5 attaches to N-terminal residues 1–139 of BECN1 (beclin1) on the BECN1 ring-like structure through amino acid residues 173–222 of P5. Subsequently, we found that P5-induced autophagosomes did not fuse with lysosomes. Becn1 silencing did not recover P5 overexpression-induced promotion of RABV replication. Mechanistically, RABV protein PΔN82 (P5) induced incomplete autophagy via the CASP2 (caspase2)-mediated signaling pathway
Conclusions
Our data indicate that P5 binding to the BECN1 ring benefits RABV replication by inducing CASP2 signaling pathway-dependent incomplete autophagy, which provides a potential target for antiviral drugs against RABV.
CT-Guided Hook-Wire Localization of Malignant Pulmonary Nodules for Video Assisted Thoracoscopic Surgery
Authors: Zhang Huijun , Li Ying , Yimin Nadier , He Zelai , Chen Xiaofeng
Published: April 2020

Objectives: Video assisted thoracoscopic surgery (VATS) can currently be used to diagnose and treat pulmonary nodules. However, intraoperative location of pulmonary nodules in VATS is challenging due to their small diameter and deep location in the pulmonary parenchyma. The purpose of this study was to report the clinical safety and effectiveness of CT-guided hook-wire for preoperative localization of malignant pulmonary nodules smaller than 1 cm in diameter.Methods: From February 2017 to January 2018, we collected the data of 80 patients with malignant pulmonary nodules less than 1 cm in diameter who underwent CT-guided hook-wire preoperative localization and VATS surgery. The effectiveness of preoperative localization was evaluated based on surgical duration, success rate of VATS surgery, and localization-related complications.Results: The diameter of pulmonary nodules were 0.85 ± 0.17 mm with a distance to the pleural surface of 19.66 ± 14.10 mm. The length of the hook-wire in the lung parenchyma was 29.17 ± 13.14 mm and hook-wire dislodgement occurred in 2 patients. Complications included 27 cases of minor pneumothorax and 18 cases of mild parenchymal hemorrhage. A significant correlation was observed between the length of the hook-wire in the lung parenchyma and mild parenchymal hemorrhage (P = 0.044). The average time of hook-wire localization was 9.0 ± 2.6 min and the average operation time for VATS was 89.02 ± 23.35 min without conversion thoracotomy.Conclusions: CT-guided hook-wire localization of the lesion during VATS resection is safe for malignant pulmonary nodules with diameter less than 1 cm.
Attitude and Practice Towards Aflatoxin Contamination in Food and Sociodemographic Factors Contributed Toward Urinary AFM1 Occurrence Among Residents in Hulu Langat, Selangor, Malaysia
Authors: Sulaiman Siti Husna , Chang Wei Lin , Jamaluddin Rosita , Sabran Mohd Redzwan
Published: April 2020

Background: Aflatoxin occurrence could be affected by several factors. This study aimed to assess the association between knowledge, attitude and practice (KAP) towards aflatoxin and sociodemographic factors with urinary AFM1 occurrence among residents in Hulu Langat, Selangor. Methods: A cross-sectional study was conducted among healthy Malaysian adults aged 18 to 60 years in six subdistricts of Hulu Langat, Selangor. Sociodemographic factors and KAP towards aflatoxin were assessed via questionnaires while morning urine sample was collected for AFM 1 analysis. Of 444 respondents, the urinary AFM 1 level was detected in 199 samples (detection rate = 44.8 %). From 37 positive samples with AFM 1 level above the detection limit of 0.64 ng/ml, the mean value was 1.23 ± 0.91 ng/ml with a range of 0.65 – 5.34 ng/ml (median = 0.89 ng/ml). The variables were examined based on the occurrence of urinary AFM 1 biomarker. Results: Findings showed that there were significant differences in urinary AFM1 occurrence across ethnicity ( p <0.01), age group ( p <0.05), monthly household income ( p <0.01), as well as attitude ( p <0.01) and practice ( p <0.05) towards aflatoxin contamination in food. Binomial logistic regression confirmed that ethnicity and monthly household income were the factors contributing to urinary aflatoxin occurrence ( p <0.01). Chinese were 3.20 times more likely to have aflatoxin exposure than the non-Chinese. Detected urinary AFM 1 was more common among household with income more than RM 1500 monthly. Conclusion: The results provided an insight to explain the variation in aflatoxin occurrence among the population. Trial registration: Ethics Committee for Research Involving Human Subjects Universiti Putra Malaysia (JKEUPM), project number: FPSK (EXP16) P047
The urgency of severity and mortality risk assessments for COVID-19: A summary from death cases in Wuhan, China
Authors: Yang Feihong , Gan Jiaohong , Zou Hao , Zhang Zhongxiang , Zhao Yan , Jiang Cheng , Xia Jian
Published: April 2020

Background To investigate the clinical characteristics of 21 death cases and evaluate potential factors of disease severity and mortality risk in COVID-19. Methods Retrospective analysis was used to study the clinical data of 21 death cases with COVID-19. The assessment of disease severity and mortality risk were conducted by APACHE II, SOFA, MuLBSTA and PSI scores. Results The age was 66±14 years-old and 15 (71.4%) were men. 16 (76.2%) patients had chronic medical illnesses. 12 (57.1%) patients were overweight. Decreased lymphocytes were observed in 17 (81.0%) patients on admission. Elevated D-dimer levels were noticed in 11 (52.4%) patients and increased much more when pneumonia deteriorated. The initial APACHE II and SOFA scores demonstrated 18 (85.7%) and 13 (61.9%) patients in middle-risk levels, respectively. MuLBSTA and PSI scores after admission showed high-risk mortality in 13 (61.9%) patients. Most patients developed sequent organ failure and finally caused death. Conclusion Older, male, overweight patients, combined with chronic medical histories, continuous decreased lymphocyte proportion and increased D-dimer might have a higher risk of death. The combination of general scoring (SOFA) and pneumonia specific scoring (MuLBSTA and PSI) after admission might be more sensitive to assess the mortality risk for critical patients in COVID-19.
Isolation and characterization of chitosan from Ugandan edible mushrooms, Nile perch scales and banana weevils for biomedical applications.
Authors: Ssekatawa Kenneth , Byarugaba Denis K. , Wampande Eddie M. , Moja Tlou N. , Nxumalo Edward , Maaza Malik , Sackey Juliet , Ejobi Francis , Kirabira John Baptist
Published: April 2020

Background: Of recent, immense attention has been given to chitosan in the biomedical field due to its valuable biochemical and physiological properties such as biodegradability, biocompatibility, non-immunogenicity, reactivity, solubility and non-toxicity. For instance, chitosan has exhibited distinguished bioactivity not limited to only antimicrobial activity but also promotion of wound healing and immune system augmentation in model animals. Therefore, chitosan has attracted application as a nano drug targeted delivery system. Traditionally, the chief source of chitosan is chitin from crab and shrimp shells obtained as waste products in the seafood industry. Chitin is also an important component of fish scales, insects and fungal cell walls, therefore, Uganda’s edible mushrooms, Nile perch scales and banana weevils can be used as alternative sources of chitin and obviously chitosan. Thus, the aim of this study was to isolate and characterize chitosan from locally available material for potential use in the biomedical field. Methods: Chitin was extracted from banana weevils, Nile perch scales and mushrooms powder by demineralization with 1.0M HCl solution, then deproteinization with 1.0M NaOH. Chitosan was prepared by treating chitin with 50% NaOH at 100°C for 8 hrs. Chitosan ash and moisture contents were determined gravimetrically while solubility was computed as percentage dry weight of suspended chitosan. FTIR was used to determine the DD while XRD was used to estimate the crystallinity of chitosan. Results: Ash and moisture contents ranged from 3.5 to 15% and 3.5 to 6.4% respectively while solubility level varied from 57 to 68%. FTIR spectra reveal high degree of similarity between locally isolated chitosan and commercial chitosan with DD ranging from 77.8 to 79.1%. X-Ray Diffraction (XRD) patterns exhibited peaks at 2θ values of 19.5° for both chitosan extracted from Mushrooms and banana weevils while chitosan from Nile perch scales registered 3 peaks at 2θ angles of 12.3°, 20.1° and 21.3° comparable to the established commercial chitosan (Sigma Aldrich) XRD pattern. Conclusion: Ash content, moisture content, DD, FTIR spectra and XRD pattern revealed that chitosan isolated from locally available materials has physicochemical properties comparable to conventional chitosan and therefore it can be used in the biomedical field.
Protective Effects of DAla2-GIP-GLU-PAL against Cognitive Deficits and Amyloid Deposition in APP/PS1 AD Mice Associated with Reduction of Neuroinflammation
Authors: Qi Jinshun , Yuan Li , Zhang Jun , Holscher Christian , Yang Jun-Ting , Wu Mei-Na , Wang Zhao-Jun , Cai Hong-Yan , Han Ling-Na , Shi Hui , Han Yu-Fei
Published: April 2020

Background

Alzhermer’s disease (AD) is a neurodegenerative disease characterized by progressive decline in cognitive function and high-density deposition of amyloid-β (Aβ) plaques in the brain. Type 2 diabetes mellitus (T2DM) is an important risk factor for AD. Glucose-dependent insulinotropic polypeptide (GIP) has been identified to be effective in T2DM treatment and neuroprotection. The present study further investigated the neuroprotective effects of a novel long lasting GIP analogue DAla2GIP-Glu-PAL in 9-month-old APP swe /PS1 dE9 (APP/PS1) AD mice.

Methods

Multiple behavioral tests including new object recognition, Y maze and Morris water maze were performed to examine the cognitive function of mice. In vivo hippocampal late-phase long-term potentiation (L-LTP) was recorded to reflect synaptic plasticity. Immunohistochemistry and immunofluorescence were used to examine the Aβ plaques and neuroinflammation in the brain. The expression levels of cAMP, S99 p-PKA, S133 p-CREB, S468 NF-κBp65 and IL-1β were detected by western blotting or ELISA.

Results

DAla2GIP-Glu-PAL effectively improved cognitive behaviors and synaptic plasticity of APP/PS1 mice, with increased new object recognition, spontaneous alternation and target quadrant swimming time, as well as enhanced in vivo hippocampal L-LTP. DAla2GIP-Glu-PAL significantly reduced Aβ deposition and inhibited astrocyte proliferation, IL-1β secretion and NF-κB activation. Besides, . DAla2GIP-Glu-PAL also up-regulated cAMP/PKA/CREB signal transduction in the hippocampus of APP/PS1 mice.

Conclusion

DAla2GIP-Glu-PAL improves cognitive behaviors, long-term synaptic plasticity and pathological damages in APP/PS1 mice, which are associated with the reduction of neuroinflammation and the up-regulation of cAMP/PKA/CREB signaling in the hippocampus. This study suggests a potential benefit of DAla2GIP-Glu-PAL in the treatment of AD.
Intravenous Calcium as a Pressor in a Swine Model of Hypoxic Lifeless Shock
Authors: Lindqwister Alexander , Lampe Joshua W. , Gould Jeffrey R. , Kaufman Christopher L. , Moodie Karen , Paradis Norman
Published: April 2020

Background: Resuscitation from hypoxic lifeless shock (LS, previously called pseudo-PEA) is often associated with hypotension refractory to catecholamine pressors. We hypothesized that this post-resuscitation state may be associated with hypocalcemia and the hypotension responsive to intravenous calcium. Results: Using pre-existing data from our hypoxic swine LS model, we measured blood pressure, hemodynamics, and electrolytes. In 9 animals with refractory hypotension we administered 37 boluses of intravenous calcium in the dosage range of 5 -20 mg. Physiological data were analyzed on a heartbeat by heartbeat basis. The midpoint of the calcium response was defined using change of curvature feature detection. Hemodynamic parameters were shifted such that the value at the midpoint was equal to zero. Comparisons were made between the average values in the time period 40-35 seconds before the bolus and 35-40 seconds after the bolus. Of the 37 administered boluses, 34 manifested a reaction in the blood pressure, with mean aortic pressure, systolic and diastolic pressures all increasing post bolus administration. Conclusions: Ionized hypocalcemia and hypotension may be common after resuscitation from hypoxic lifeless shock. Administration of intravenous calcium may be associated with a pressor-like response. Hypocalcemia is an etiology for hypotension, and intravenous calcium as a therapy in this setting should be further investigated.
Electrically stimulable indium tin oxide plate for long-term in vitro cardiomyocyte culture
Authors: Moon Sung-Hwan , Cho Young-Woo , Shim Hye-Eun , Choi Jae-Hak , Jung Chan-Hee , Hwang In-Tae , Kang Sun-Woong
Published: April 2020

Background: We investigated whether electrical stimulation via indium tin oxide (ITO) could enhance the in vitro culture of neonatal rat ventricular myocytes (NRVMs), which are important in vitro models for studying the mechanisms underlying many aspects of cardiology.Methods: Cardiomyocytes were obtained from 1-day-old neonatal rat heart ventricles. To evaluate function of NRVMs cultured on ITO with electrical stimulation, the cell viability, change of cell morphology, immunochemistry using cardiac-specific antibodies, and gene expression were tested.Results: Defined sarcomeric structure, cell enlargement, and increased distribution of NRVMs appeared in the presence of electrical stimulation. These characteristics were absent in NRVMs cultured under standard culture conditions. In addition, the expression levels of cardiomyocyte-specific and ion channel markers were higher in NRVMs seeded on ITO-coated dishes than in the control group at 14 days after seeding. ITO-coated dishes could effectively provide electrical cues to support the in vitro culture of NRVMs.Conclusions: These results provide supporting evidence that electrical stimulation via ITO can be effectively used to maintain culture and enhance function of cardiomyocytes in vitro.
Health-related quality of life of people living with HIV/AIDS: the role of social inequalities and disease-related factors
Authors: Nigusso Fikadu Tadesse , Mavhandu-Mudzusi Azwihangwisi Helen
Published: April 2020

Background: Health-related quality of life (HRQoL) serves as a direct measure of individuals’ health, life expectancy and the impact that the utilisation of health care has on quality of life. The purpose of this study is to assess the HRQoL of people living with HIV and AIDS, and to ascertain its association with the social inequalities and clinical determinants among people living with HIV in Benishangul Gumuz Regional State, Ethiopia.Methods: A cross-sectional study was conducted between December 2016 and February 2017; 390 people at two referral hospitals and three health centres participated in the study. The Patient-Reported Outcomes Measurement Information System Global Health Scale (PROMIS Global 10) was used to measure key HRQoL domains. Physical Health Summary (PHS) and Mental Health Summary (MHS) scores were employed. PHS and MHS scores below 50 (the standardised mean score) were determined to be poor and above 50 to be good. Bivariate and multivariate logistic regression analyses were used to identify factors associated with PHS and MHS scores.Results: This study included 259 (66.4%) females and 131 (33.6%) males. The PHS scores ranged from 16.2 to 67.7 with a mean of 48.8 (SD = 8.9). Almost 44.6% of the study population has a PHS score of below 50; the MHS scores ranged from 28.4 to 67.6 with a mean of 50.8 (SD = 8.1). About 41.8% of the study population has an MHS score of below 50. Unemployment, household food insecurity and comorbidities with HIV were associated with both poor PHS and poor MHS scores. The demographic factors associated with poor PHS scores were being a member of the Oromo ethnic group and having non-Christian religious affiliations; while age of below 25 years were inversely associated with poor PHS. The least wealth index score was also associated with a poor MHS score.Conclusion: Overall, socioeconomic inequalities and HIV-related clinical factors play an important role in improving the HRQoL of PLWHA. Many of these determinants are alterable risk factors. Appropriate strategies can improve the holistic management of chronic HIV care and maximise PLWHAs’ HRQoL. Such strategies require the adoption of comprehensive interventions, including policies and programmes that would improve the health, wellbeing and livelihood of PLWHAs.
Effects of oral contraceptives on the quality of life of women with polycystic ovary syndrome: a crossover randomized controlled trial
Authors: Amiri Mina , Nahidi Fatemeh , Bidhendi-Yarandi Razieh , Khalili Davood , Tohidi Maryam , Tehrani Fahimeh Ramezani
Published: April 2020

Background and objective A limited number of studies have evaluated the effects of oral contraceptives (OCs) on the quality of life (QOL) of polycystic ovary syndrome (PCOS) patients. This study aimed to compare the effects of using OCs containing levonorgestrel (LNG) and those containing desogestrel (DSG), cyproterone acetate (CPA) or drospirenone (DRSP) for 6 months on the QOL with PCOS. Methods In this crossover randomized controlled 6-arm trial, 200 eligible patients with PCOS scheduled for OC therapy were randomly assigned to one of the 6 study arms. All 6 arms include two 6-month treatment periods, one period with OCs containing LNG, and the other with each of the 3 OCs containing DSG, CPA, or DRSP. Outcomes of interest were the total score of QOL and its domains. Results Finally, a total of 88 patients were analyzed for this study. The results showed that use of OCs containing DSG, CPA, and DRSP for 3 months was not associated with significant differences in the total scores of QOL compared to those OCs containing LNG, whereas, after 6 months of treatment, patients treated with OCs containing CPA had more improvements in their total scores of QOL, in comparison to OCs containing LNG (P < 0.042). We found no significant differences in QoL domains, including psychosocial–emotional, self-image, fertility, sexual function, hirsutism, and obesity-menstrual disorders after 3- 6 months of treatment with DSG, CPA, or DRSP, compared to LNG. The sequence and period effects were not significant in any of the analyses at 3 and 6 months of treatment. The carry-over effect was not significant for most outcomes assessed. Conclusions This crossover study demonstrated non-inferiority of OCs with newer generation progestins on different domains of QOL, in comparison with older compounds, although usage of products containing CPA was significantly associated with more improvement in total QOL of PCOS patients, compared to those containing LNG after 6-month of treatment.
Dietary nutrient intake related to higher grade cervical intraepithelial neoplasia risk: A Chinese population-based study
Authors: Wang Zhe , Yang Aimin , Yang Jing , Zhao Weihong , Wang Zhilian , Wang Wei , Wang Jintao , Song Jinghui , Li Li , Lv Weiguo , Li Dongyan , Liu Huiqiang , Wang Chen , Hao Min
Published: April 2020

Background Dietary nutrient intake plays a significant role in carcinogenesis. Few studies have investigated the association between dietary nutrient intake and cervical intraepithelial neoplasia (CIN) risk in China.Methods Data on 2,304 women from an ongoing cohort comprising 40,000 women from China in 2014 were included. We randomly selected 218 out of 2304 people as subjects during 2019. All participants were surveyed through in-person interviews, physical examinations, and laboratory tests. Clinical data were obtained from physical examinations and laboratory tests. Dietary intakes were assessed using a semiquantitative food frequency questionnaire. Nutrition intakes from 26 food sources were calculated using a comprehensive validated database. Descriptive statistics were used to describe the frequency and proportion, and mean and standard deviation of the demographic characteristics. Characteristics were examined for significant differences, and Pearson chi-square tests were used for categoric variables. Logistic regression was used to obtain odds ratios (ORs) and confidence intervals (CIs) for CIN risk in each nutritional ingredient quartile relative to that in the highest quartile.Results The food frequency questionnaire exhibited acceptable reproducibility and reasonable validity in assessing nutrient intakes among these women. After adjusting for multiple confounders, several dietary nutrients showed significant associations with CIN2 + risk. Low dietary folate intake was associated with the risk of CIN2+ (first versus fourth quartile: OR = 1.55, 95% CI: 1.03–2.33). Similar results were also observed for vitamin B6 (OR = 1.63, 95% CI: 1.08–2.46), vitamin C (OR = 1.59, 95% CI: 1.05–2.42), niacin (OR = 1.65, 95% CI: 1.08–2.51), and vitamin K (second versus fourth quartile: OR = 1.60, 95% CI: 1.05–2.44).Conclusions Low folate; vitamin B6, C, and K; and niacin intakes were associated with CIN2 + risk. Nutrients may influence the development of higher grade CIN and cervical cancer.Trial registration: The study was registered in the Chinese Clinical Trial Register (ChiCTR-ROC-15006479) (http://www.chictr.org.cn).
Recurrent Synovitis of Hip and MEFV Gene Related Arthritis in Children
Authors: Salehzadeh Farhad , Mirzarahimi Mehrdad
Published: April 2020

Background : Recurrent and relapsing arthritis has been proposed to describe a group of arthritis with recurring and periodic nature, in which the joints are intermittently involved. This study reports three non-FMF patients with heterozygous MEFV gene mutations and an extraordinary arthritis as a recurrent synovitis of hip (RSH) Methods : During 16-years from 2003 to 2019 at pediatric rheumatologic clinic among 195 recorded files with chronic oligoarthritis, 3 patients with diagnosis of recurrent synovitis of hip (RSH) were reviewed thoroughly. Peripheral blood was collected from patients and the samples were screened for the 12 common MEFV gene pathogenic variants. Results: This study included three patients, two female and one male with relapsing idiopathic arthritis that has been located on hip joints as a sole manifestation and pathologic findings of MEFV mutations as follow: A744S, V726A, and R761H. Conclusion : On the basis of possible role of MEFV gene in different rheumatic disease, MEFV gene related arthritis may be considered as a background of RSH particularly in Mediterranean area.
Effect of Electroacupuncture on Spinal Cord Injury in Mice: Inhibition Of Inflammatory Response and Oxidative Stress via ApoE and Nrf2
Authors: Dai Ni , Tang Chenglin , Zhao Hongdi , Dai Pan , Huang Siqin
Published: April 2020

Background: Spinal cord injury (SCI) is a catastrophic central nervous system disease. Inflammatory response and oxidative stress are two critical factors in the pathophysiological process of SCI and closely involved with Apolipoprotein E(ApoE) and Nuclear factor erythroid 2-related factor (Nrf2). Electroacupuncture (EA) has perfectly neuroprotective effect on SCI. However, the underlying mechanism by which EA mediates the inflammatory response and oxidative stress is not completely elucidated. In the present study, we investigated the signaling pathways that EA regulates inflammatory response and oxidative stress through elevation of ApoE and Nrf2 after SCI.Methods: C57BL/6 Wide Type (WT) mice and ApoE -/- mice were subjected to SCI model by a serrefine clamping. Neurological function was detected by BMS scores, ultrastructure of demyelinationed axons was observed by transmission electron microscopy. ApoE, pro- and anti- inflammatory cytokines, oxidative stress-relevant proteins were determined by histochemistry technology. Two-way ANOVA was applied to BMS scores. One-way ANOVA and Bonferroni's multiple comparison test were used to analyse differences among groups.Results: BMS scores were increased gradually and demyelinated axons were improved by EA gradually with the expression of ApoE. EA can inhibit inflammatory response by activation of ApoE, which decreased pro-inflammatory cytokines(TNF-α, IL-6, and IL-1β) expression and increased anti-inflammatory cytokines(IL-10 and TGF-β1).Meanwhile, EA can also inhibit oxidative stress by elevation of Nrf2,which induced HO-1 and NQO1 expression in WT and ApoE -/- mice.Conclusions: EA is a reliable treatment for promoting functional recovery of SCI. Thesynergisticrole of ApoE and Nrf2 in EA regulating inflammatory response and oxidative stress is decisiveto recovery after SCI.