bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of tobacco and alcohol use in the interaction of social determinants of non-communicable diseases in Nepal: a systems perspective
Authors: Sharma Sudesh Raj , Matheson Anna , Lambrick Danielle , Faulkner James , Lounsbury David W , Vaidya Abhinav , Page Rachel
Published: April 2020

Background: Tobacco and alcohol use are major behavioural risks in developing countries like Nepal, which are contributing to a rapid increase in non-communicable diseases (NCDs). This causal relationship is further complicated by the multi-level social determinants such as socio-political context, socio-economic factors and health systems. The systems approach has potential to facilitate understanding of such complex causal mechanisms. The objective of this paper is to describe the role of tobacco and alcohol use in the interaction of social determinants of NCDs in Nepal. Method: The study was a qualitative study design guided by the Systemic Intervention methodology. The study involved key informant interviews (n=63) and focus group discussions (n=12) at different levels (policy, district and/or community) and was informed by the adapted Social Determinants of Health Framework . The data analysis involved case study-based thematic analysis using framework approach and development of causal loop diagrams. The study also involved three sense-making sessions with key stakeholders. Results: Three key interacting themes emerged during the data analysis. Widespread availability of tobacco and alcohol products contributed to the use and addiction of tobacco and alcohol. Low focus on prevention by health systems and policy influence of tobacco and alcohol companies were the major contributors to the problem. Gender and socio-economic status of families/communities were identified as key social determinants of tobacco and alcohol use. These interacting themes were utilised to develop causal loop diagrams and system archetypes. Conclusion: Tobacco and alcohol use facilitated interaction of the social determinants of NCDs in the context of Nepal. Socio-economic status of families was both driver and outcome of tobacco and alcohol use. Health system actions to prevent NCDs were delayed mainly due to lack of system insights and policy influence. A multi-sectoral response led by the health system is urgently needed.
M1 macrophage features in severe Plasmodium falciparum malaria patients with pulmonary oedema
Authors: Klinkhamhom Aekkarin , Glaharn Supattra , Sris Charit , Ampawong Sumate , Krudsood Srivicha , Ward Stephen A. , Viriyavejakul Parnpen
Published: April 2020

Background Pulmonary oedema (PE) is a serious complication of severe P. falciparum malaria which can lead to acute lung injury in severe cases. Lung macrophages are activated during malaria infection due to a complex host-immune response. The molecular basis for macrophage polarisation is still unclear but understanding the predominant subtypes could lead to new therapeutic strategies where the diseases present with lung involvement. The present study was designed to study the polarisation of lung macrophages, as M1 or M2 macrophages, in the lungs of severe P. falciparum malaria patients with and without evidence of PE. Methods Lung tissue samples, taken from patients who died from severe P. falciparum malaria, were categorised into severe malaria with PE and without PE (non-PE). Expression of surface markers (CD68- all macrophages, CD40- M1 macrophage and CD163- M2 macrophage) on activated lung macrophages was used to quantify M1/M2 macrophage subtypes. Results Lung injury was demonstrated in malaria patients with PE. The expression of CD40 (M1 macrophage) was prominent in the group of severe P. falciparum malaria patients with PE ( p < 0.05), whereas there was no difference observed for CD163 (M2 macrophage) between PE and non-PE groups. Conclusions The study demonstrates M1 polarisation in lung tissues from severe P. falciparum malaria infections with PE. Understanding the nature of macrophage characterisation in malaria infection may provide new insights into therapeutic approaches that could be deployed to reduce lung damage in severe P. falciparum malaria.
Serum IgG-induced microglial activation enhances neuronal cytolysis via the NO/sGC/PKG pathway in children with opsoclonus-myoclonus syndrome and neuroblastoma
Authors: Ding Xu , Yang Wei , Ren Qinghua , Hu Jiajian , Yang Shen , Han Wei , Wang Jing , Wang Xu , Wang Huanmin
Published: April 2020

Background: Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disease. Some children with OMS also have neuroblastoma (NB). We and others have previously documented that serum IgG from children with OMS and NB induces neuronal cytolysis and activates several signaling pathways. However, the mechanisms underlying OMS remain unclear. Here we investigated whether nitric oxide (NO) from activated microglias and its cascade contribute to neuronal cytolysis in pediatric OMS.Methods: The activation of cultured cerebral cortical and cerebellar microglias incubated with sera or IgG isolated from sera of children with OMS and NB was measured by the expression of the activation marker, cytokines and NO. Neuronal cytolysis was determined after exposing to IgG-treated microglia conditioned media. Using inhibitors and activators, the effects of NO synthesis and its intracellular cascade, namely soluble guanylyl cyclase (sGC) and protein kinase G (PKG), on neuronal cytolysis were evaluated.Results: Incubation with sera or IgG from children with OMS and NB increased the activation of cerebral cortical and cerebellar microglias, but not the activation of astrocytes or the cytolysis of glial cells. Moreover, the cytolysis of neurons was elevated by conditioned media from microglias incubated with IgG from children with OMS and NB. Furthermore, the expression of NO, sGC and PKG was increased. Neuronal cytolysis was relieved by the inhibitors of NO signaling, while neuronal cytolysis was exacerbated by the activators of NO signaling but not proinflammatory cytokines. The cytolysis of neurons was suppressed by pretreatment with the microglial inhibitor minocycline, a clinically tested drug. Finally, increased microglial activation did not depend on the Fab fragment of serum IgG.Conclusions: Serum IgG from children with OMS and NB potentiates microglial activation, which induces neuronal cytolysis through the NO/sGC/PKG pathway, suggesting an applicability of microglial inhibitor as a therapeutic candidate.
Cattle gastrointestinal nematode egg-spiked faecal samples: high recovery rates using the Mini-FLOTAC technique
Authors: Amadesi Alessandra , Bosco Antonio , Rinaldi Laura , Cringoli Giuseppe , Claerebout Edwin , Maurelli Maria Paola
Published: April 2020

Background : Faecal egg count (FEC) techniques are commonly used to detect gastrointestinal nematode (GIN) in cattle and to determine anthelmintic efficacy/resistance through the faecal egg count reduction test (FECRT). Mini-FLOTAC is one of the techniques recommended for a standardised FEC/FECRT of helminth eggs in cattle. However, only one paper evaluated the recovery rate of GIN eggs by Mini-FLOTAC (compared to McMaster and modified-Wisconsin) in cattle, using only the level of contamination of 200 eggs per gram (EPG) of faeces and using GIN eggs collected from goat faeces to spike faecal samples from cattle. To further study the recovery rate of added GIN eggs from cattle, this study was conducted in two laboratories, one in Belgium and one in Italy to evaluate sensitivity, accuracy, precision and reproducibility of Mini-FLOTAC and McMaster (at two reading levels: grids and chambers) for the detection of GIN eggs in spiked bovine faecal samples. Methods: In both countries, spiked cattle faecal samples with five different levels of egg contamination (10, 50, 100, 200 and 500 EPG) of GINs were used. The study was performed in both laboratories by the same expert operator and using the same standard operating procedures (SOPs) for Mini-FLOTAC and McMaster. Sensitivity, accuracy and precision were calculated for each technique and for each level of contamination. Moreover, statistical analyses were performed to evaluate differences between performances of techniques used. Results : Mini-FLOTAC had a higher sensitivity (100% at all EPG levels for Mini-FLOTAC vs 0-66.6% for McMaster chambers and grids at levels <100 EPG), a higher accuracy (98.1% mean value for Mini-FLOTAC vs 83.2% for McMaster grids and 63.8% for McMaster chambers) and a lower coefficient of variation (10.0% for Mini-FLOTAC vs 47.5% for McMaster grids and 69.4% for McMaster chambers) than McMaster. There was no significant difference between the recovery of GIN eggs from the two studies performed in Belgium and in Italy. Conclusions : The high GIN eggs recovery rate detected by Mini-FLOTAC and the similar results obtained in Belgium and in Italy indicated that the diagnostic performance of a FEC technique was not regard to the laboratory environment.
Pseudoscorpion Wolbachia symbionts: Diversity and Evidence for a New Supergroup S
Authors: Lefoulon Emilie , Clark Travis , Borveto Fanni , Perriat-Sanguinet Marco , Moulia Catherine , Slatko Barton , Gavotte Laurent
Published: April 2020

Background Wolbachia are the most widely spread endosymbiotic bacteria, present in a wide variety of insects and two families of nematodes, but as of now, relatively little genomic data has been available. The Wolbachia symbiont can be parasitic, as described for many arthropod systems, an obligate mutualist, as in filarial nematodes or a combination of both in some organisms. They are currently classified into 16 monophyletic lineage groups ("supergroups"). Although the nature of these symbioses remains largely unknown, expanded Wolbachia genomic data will contribute to understanding their diverse symbiotic mechanisms and evolution. Results This report focuses on Wolbachia infections in three pseudoscorpion species infected by two distinct groups of Wolbachia strains , based upon multi-locus phylogenies. Geogarypus minor harbours w Gmin and Chthonius ischnocheles harbours w Cisc, both closely related to supergroup H, while Atemnus politus harbours w Apol, a member of a novel supergroup S along with Wolbachia from the pseudoscorpion Cordylochernes scorpioides ( w Csco), most closely related to Wolbachia supergroups C and F. Using target enrichment by hybridization with Wolbachia -specific biotinylated probes to capture large fragments of Wolbachia DNA, we produced two draft genomes of w Apol. Annotation of w Apol highlights presence of a biotin operon, which is incomplete in many sequenced Wolbachia genomes. Conclusions The present study highlights at least two symbiont acquisition events among pseudoscorpion species. Phylogenomic analysis indicates that the Wolbachia from Atemnus politus ( w Apol), forms a separate supergroup ("S") with the Wolbachia from Cordylochernes scorpioides (w Csco). Interestingly, the biotin operon, present in w Apol, appears to have been horizontally transferred multiple times along Wolbachia evolutionary history.
Evaluation of the effect of an "Internet plus medical"-based health management service model in patients with nonalcoholic fatty liver disease
Authors: Yang Yan , Tian Cui-Huan , Dai Jun , Zhang Wei , Li Shu-Qing , Min Xiang , Wang Yan-Yan , Cao Juan
Published: April 2020

Objectives: To observe the effect of an "Internet plus medical"-based health management service model in patients with nonalcoholic fatty liver disease (NAFLD) and to explore an effective model for NAFLD health management to provide a reference for NAFLD treatment and nursing. Methods: The present study was a randomized, controlled, parallel-group comparison trial. A total of 519 patients with NAFLD were randomly assigned to a routine health education group (N=258) or a health management platform group (N=261). The routine health education group received routine health education, and the health management platform group was treated with the "Internet plus medical"-based health management service model to manage NAFLD. The new model provides closed-loop services for the prevention and rehabilitation of NAFLD through the process of grouping, filing, evaluating, planning, intervening, assessing stage and following up. The two groups were observed for 24 weeks. The results of basic indicators, laboratory indicators, body composition analyses, controlled attenuation parameters (CAP) and quality of life assessment questionnaires were used as evaluation indices. All data of the participants were collected and analyzed prior to and following the intervention, and the differences between the two groups were compared. Results: Compared with the routine health education group, the NAFLD health management service model based on “Internet plus medical” treatment effectively reduced the weight (-3.80±3.11vs -0.12±3.42, P =0.047), body mass index (BMI) (-1.73±1.20 vs -0.14±1.68, P =0.031), CAP (-48.42±10.13 vs 4.13±7.45, P =0.044), aspartate transaminase (AST)/alanine aminotransferase (ALT) value (0.18±0.37 vs 0.04±0.11, P = 0.037), body fat content(-2.24±2.58 vs -0.86±2.78, P =0.194) and visceral fat area(-10.87±15.34 vs -0.55±19.13, P =0.047) of NAFLD patients and improve the quality of life of NAFLD patients in terms of physiological role(96.59 ±11.31 vs 90.69 ± 13.49, P =0.027), vitality (86.57±6.07 vs 81.94±5.78, P =0.001) and general health(78.05±6.35vs 73.61±10.12, P =0.044 ). Conclusions: The results of the present study preliminarily confirm the validity and development prospects of the "Internet plus medical"-based health management service model in NAFLD. This finding suggests that the model is an evidence-based model of health education and management for NAFLD prevention in China.
IC100: A Novel Anti-Asc Monoclonal Antibody Improves Functional Outcomes In An Animal Model Of Multiple Sclerosis
Authors: Desu Haritha L , Plastini Melanie , Illiano Placido , Bramlett Helen M , Dietrich W. Dalton , Vaccari Juan Pablo de Rivero , Brambilla Roberta , Keane Robert W.
Published: April 2020

Background The inflammasome adaptor apoptosis-associated speck-like protein containing a CARD (ASC) is involved in immune signaling by bridging the interactions between inflammasome sensors and caspase-1. Strong experimental evidence has shown that ASC-/- mice are protected from disease progression in animal models of multiple sclerosis (MS), suggesting that targeting inflammasome activation via ASC inhibition may be a promising therapeutic strategy in MS. Thus, the goal of our study is to test the efficacy of IC100, a novel humanized antibody targeting ASC, in preventing and/or suppressing disease in the experimental autoimmune encephalomyelitis (EAE) model of MS. Methods We employed the EAE model of MS where disease was induced by immunization of C57BL/6 mice with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55). Mice were treated with vehicle or increasing doses of IC100 (10, 30 and 45 mg/kg) and clinical disease course was evaluated up to 35 days post EAE induction. Immune cell infiltration into the spinal cord and microglia responses were assessed.Results We show that IC100 treatment reduced the severity of EAE when compared to vehicle-treated controls. At a dose of 30 mg/kg, IC100 significantly reduced the number of CD4+ and CD8+ T cells and CD11b+MHCII+ activated myeloid cells entering the spinal cord from the periphery, and reduced the number of total and activated microglia. Conclusions These data indicate that IC100 suppresses the immune-inflammatory response that drives EAE development and progression, thereby identifying ASC as a promising target for the treatment of MS as well as other neurological diseases with a neuroinflammatory component.
Reducing miR485-3p ameliorates Alzheimer`s disease pathology by regulation of amyloid beta and neuro-inflammation
Authors: Koh Han Seok , Jang Hannah , Tae Sookil , Lee mi-sun , Min Jae-Woong , Mun Hui jin , Lee Ji na , Lee Hyo Jin , KIM Dae Hoon , Cho Hyun-Jeong , Ryu Jin-Hyeob
Published: April 2020

Background

Alzheimer`s disease (AD) is a progressive neurodegenerative disease worldwide. Accumulation of amyloid-β (Aβ), neurofibrillary tangles and neuroinflammation play the important neuro-pathology in patients with AD. miRNA is multifunctional and involved in physiological and pathological processes. Recently, microRNAs have been linked to neurodegenerative diseases. However, it is little known whether miRNA dysregulation contributes to AD pathology progression such as Ab processing, phagocytosis and neuroinflammation. Here, we identify miR485-3p as a novel modulator of AD pathology in 5XFAD mice.
Methods

To study the role of miR485-3p in AD, we used in control or miR485-3p antisense oligonucleotides (miR485-3p ASO) injected 5XFAD mouse model. Changes of Ab processing, clearance and inflammation were analyzed by biochemical method in vitro and in vivo.
Results

This study suggests that miR485-3p, a novel miRNA targeting SIRT1 may contribute to pathogenesis in an AD mouse. We found SIRT1 is significantly reduced in the precentral gyrus of Alzheimer patient`s and in 5XFAD mice. To determine whether the inhibition of miRNA 485-3p would affect AD pathology, we studied the effect of the antisense oligo in the brain of 5XFAD mice through direct intracerebral ventricular injection with miR485-3p ASO. We demonstrated that miR485-3p ASO significantly reduced Aβ plaque and amyloid biosynthetic enzyme. Importantly, the attenuation of Aβ plaques through miR485-3p ASO was mediated through Aβ phagocytic activity of glial cells, by which it can directly target CD36. MiR485-3p ASO also decreased inflammatory responses. Collectively, these responses inhibited neuronal loss caused by Aβ lead to improvements of cognitive impairment.
Conclusion

Our data provide evidence for the molecular mechanisms which underlie the miR485-3p ASO responses in an AD mouse model. These results suggest that attenuating miRNA 485-3p levels might represent a novel therapeutic approach in AD.
Impacts of Remote Ischemic Preconditioning on Major Adverse Kidney Events Within 90 Days After Open Total Aortic Arch Replacement: A Post-Hoc Analysis of a Previous Randomized Controlled Trial
Authors: Chen Yimeng , Wang Guyan , Zhou Hui , Yang Lijing , Zhang Congya , Yang Xiying , Lei Guiyu
Published: April 2020

Background In the previous randomized controlled trial by our research group, we evaluated the effect of remote ischemic preconditioning (RIPC) in 130 patients (65 per arm) on acute kidney injury (AKI) within 7 days of open total aortic arch replacement. Significantly fewer RIPC-treated patients than sham-treated patients developed postoperative AKI, and, epically, RIPC significantly reduced serious AKI (stage II–III). However, the long-term effect of RIPC in patients undergoing open total aortic arch replacement is unclear.Methods This study was a post-hoc analysis. We aimed to assess the roles of RIPC in major adverse kidney events (MAKE), defined as consisting persistent renal dysfunction, renal replacement therapy and mortality, within 90 days after surgery in patients receiving open total aortic arch replacement.Results In this 90-day follow-up study, data were available for all study participants. We found that RIPC failed to improve the presence of MAKE within 90 days after surgery (RIPC: 7 of 65[10.8%]) vs sham: 15 of 65[23.1%]; P = 0.061). In those patients who developed AKI after surgery, we found that the rate of MAKE within 90 days after surgery differed between the RIPC group and the sham group (RIPC: 4 of 36[11.2%]; sham: 14 of 48[29.2%]; P = 0.046).Conclusions At 90 days after open total aortic arch replacement, we failed to find a difference between the renoprotective effects of RIPC and sham treatment. The effectiveness or ineffectiveness of RIPC should be further investigated in a large randomized sham-controlled trial.Trial registration This study was approved by the Ethics Committee of Fuwai Hospital (No. 2016–835) and our previous study was registered at clinicaltrials.gov before patient enrollment (NCT03141385; principal investigator: G.W.; date of registration: March 5, 2017).
Thyroid hormone mediates cardioprotection against postinfarction remodeling and dysfunction through the IGF-1/PI3K/AKT signaling pathway
Authors: Zeng Bin , Liao Xiaoting , Liu Lei , Zhang Caixia , Ruan Huaiyu
Published: April 2020

Background
Severe cardiovascular diseases, such as myocardial infarction or heart failure, can alter thyroid hormone (TH) secretion and peripheral conversion, leading to low triiodothyronine (T3) syndrome. Accumulating evidence suggests that TH has protective properties against cardiovascular diseases and that treatment with TH can effectively reduce myocardial damage after myocardial infarction (MI). However, the potential mechanisms are not clear. This study was designed to investigate the effect of T3 pretreatment on cardiac function and pathological changes in mice subjected to MI and the underlying mechanisms.
Methods
Adult male C57BL/6 mice underwent surgical ligation of the left anterior descending coronary artery (LAD) (or sham operation) to establish a myocardial infarction model. T3, BMS-754807 (inhibitor of insulin-like growth factor-1 receptor (IGF-1R)) or vehicle was administered before surgery.
Results
Compared with the MI group, the T3 pretreatment group exhibited significant attenuation of the myocardial infarct area, inhibition of cardiomyocyte apoptosis and fibrosis, and improved left ventricular function after MI. In addition, T3 exhibited an enhanced potency to stimulate angiogenesis and exert anti-inflammatory effects by reducing the levels of serum inflammatory cytokines after myocardial infarction. However, all of these protective effects were inhibited by the IGF-1R inhibitor BMS-754807. Moreover, the protein expression of IGF-1/PI3K/AKT signaling-related proteins, such as IGF-1, IGF-1R, phosphorylated PI3K (p-PI3K) and p-AKT was significantly upregulated in MI mice that received T3 pretreatment, and BMS-754807 pretreatment blocked the upregulation of the expression of these signaling-related proteins.
Conclusion
T3 pretreatment can protect the heart against dysfunction post-MI through its anti-apoptotic, anti-fibrotic, anti-inflammatory and angiogenesis-stimulating effects, which may be mediated by the activation of the IGF-1/PI3K/AKT signaling pathway.
Analysis of Risk Factors of Severe COVID-19 Patients
Authors: Yin Qin , Fu Zhen , Xie Jiao , Yang Jie , Li Fengqin , Zhu Wangcai , Yu Yihan , Zhang Jixian
Published: April 2020

Objective: To explore relevant risk factors for severity of patients with novel coronavirus pneumonia (COVID-19).Methods: The clinical data of 292 patients with COVID-19 admitted to Hubei Provincial Hospital of Integrated Chinese & Western Medicine from January 1, 2020 to February 29, 2020 were analyzed retrospectively. Patients were divided into mild or severe group according to the Guidance for Corona Virus Disease 2019 (7th version) released by the Chinese National Health Committee. The clinical data were collected at the time of admission, including demographics, clinicalcharacteristics, laboratory test results, imaging characteristics and outcome of treatment. We applied univariable and multivariable logistic regression methods to explore the risk factorsassociated with severity of the disease.Results: The median age of patients in the severe group((68.19 ± 12.51)years) was significantly older than mild group((54.14 ± 13.62)years). The male sex was more predominant in severe group (63.45%) than that of mild group (38.1%). There were more smokers (8.97% vs 1.36%) and drinkers (4.14% vs 0%) in severe group than that of mild group. Patients in the severe group had more underlying diseases. Hypertension(48.97% vs 23.81%),coronary heart disease (22.07% vs 1.36%, P < 0.0001), chronic obstructive pulmonary disease (6.21% vs 1.36%), malignant tumor (7.59% vs 2.04%) and chronic kidney disease (3.45% vs 0%) were more frequent in severe group than in mild group.The dyspnea, chest tightness and dry cough were more common in severe group (43.45%, 66.9% and 66.21%) than in mild group (23.13%, 44.22% and 53.74%). Abnormality of chest radiography were more frequent in the severe group, there were more ground glass opacities, consolidation of lung and white lung in the severe cases (88.97%, 44.07% and 46.21%) than in mild cases (78.91%, 19.05% and 2.04%). Patients in the severe group were more likely to receive methylprednisolone, oxygen therapy and mechanical ventilation. Lasso algorithm showed that age, C-reactive protein (CRP), creatine kinase (CK) and α-hydroxybutyrate dehydrogenase (α-HBDB) were the independent risk factors for severeCOVID-19, and CD4+T lymphocyte count was the protective factor.Conclusion: This large-scale retrospective study of 292 COVID-19 patients revealed that age, CRP, CK,α-HBDB and CD4+T lymphocyte were independent risk factors for severity of COVID-19. Identifying patients with risk factors at an early stage of the disease are helpful for outcome prediction and clinical management.
Assessing longitudinal and cross-sectional effects of age on adult obesity in an Iranian population: results from a large population-based cohort study
Authors: Alhossaini Mahsa Rafiee , Kazemnejad Anoshirvan , Zayeri Farid , Sadeghi Masoumeh
Published: April 2020

The authors have requested that this preprint be removed from Research Square.
Resistance to ventricular fibrillation predicted by the QRS/QTc - ratio in an intact rat model of hypothermia/rewarming
Authors: Dietrichs Erik Sveberg , Kondratiev Timofey , McGlynn Karen , Smith Godfrey , Tveita Torkjel
Published: April 2020

Background
Accidental hypothermia is associated with increased risk for arrhythmias, including ventricular fibrillation and cardiac arrest. Recently QRS/QTc was proposed as an ECG-marker, where decreasing QRS/QTc ratio could predict ventricular arrhythmias in such patients. If reliable it should also predict nonappearance of arrhythmias, observed in species like rat that regularly tolerate prolonged hypothermia, during sustained sinus rhythm.
Methods
A rat model designed for studying cardiovascular function during cooling, 4 h experimental hypothermia (15 °C core temperature) and subsequent rewarming was used, and ECG recorded throughout the experimental protocol.
Results
No ventricular arrhythmias occured and there was no sign of a hypothermia-induced reduction of QRS/QTc values during moderate hypothermia. The ratio steadily increased throughout the entire cooling period and remained above normothermic baseline until rewarmed.
Conclusion
Different from the high incidence of hypothermia-induced ventricular arrhythmias in accidental hypothermia patients, where QRS/QTc ratio is decreased in moderate hypothermia, hypothermia and rewarming of rats is not associated with increased risk for ventricular fibrillation. This resistance to lethal hypothermia-induced arrhythmias was predicted by the QRS/QTc ratio.
Mechanisms underlying the predictive power of high skeletal muscle uptake of FDG in Amyotrophic Lateral Sclerosis
Authors: Marini Cecilia , Cossu Vanessa , Bonifacino Tiziana , Bauckneht Matteo , Torazza Carola , Bruno Silvia , Castellani Patrizia , Ravera Silvia , Milanese Marco , Venturi Consuelo , Carlone Sebastiano , Piccioli Patrizia , Emionite Laura , Morbelli Silvia , Orengo Anna Maria , Donegani Maria Isabella , Miceli Alberto , Raffa Stefano , Marra Stefano , Cortese Katia , Grillo Federica , Fiocca Roberto , Bonanno Giambattista , Sambuceti Gianmario
Published: April 2020

BackgroundUsing a computational approach to PET/CT images, we recently reported that enhanced 18F-fluorodeoxyglucose (FDG) uptake in skeletal muscles predicts aggressiveness and outcome in patients with amyotrophic lateral sclerosis (ALS). The present experimental study aimed to assess the mechanisms underlying the predictive potential of this metabolic shift in SOD1G93A mice as a model of ALS.Methods.The study included 15 SOD1G93A mice and 15 wild-type mice (around 120-days-old). Mice were submitted to micro-PET imaging. Enzymatic pathways and response to oxidative stress were evaluated in harvested quadriceps and hearts by biochemical, immunohistochemical and immunofluorescence analysis. Colocalization between the endoplasmic reticulum (ER) and the fluorescent FDG analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) were performed in fresh skeletal muscle sections. Finally, mitochondrial ultrastructure and bioenergetic evaluation were evaluated in harvested quadriceps and hearts.ResultsFDG retention was significantly higher in hindlimb skeletal muscles of symptomatic SOD1G93A mice with respect to control ones. This difference was not explained by any acceleration in cytosolic glucose degradation through glycolysis or pentose phosphate pathway (PPP). Similarly, it was independent of inflammatory infiltration. Rather, the high FDG retention in SOD1G93A skeletal muscle was associated with an accelerated generation of reactive oxygen species. This redox stress selectively involved the ER and the local PPP triggered by hexose-6P-dehydrogenase. ER involvement was confirmed by the colocalization of the 2-NBDG with a vital ER tracker. The oxidative damage in transgenic skeletal muscle was associated with a severe impairment in the crosstalk between ER and mitochondria combined with alterations in mitochondrial ultrastructure and fusion/fission balance. The expected respiratory damage was confirmed by a deceleration in ATP synthesis and oxygen consumption rate. These same abnormalities were represented to markedly lower degree in the myocardium, as a sample of non-voluntary skeletal muscle.ConclusionSkeletal muscle of SOD1G93A mice reproduces the increased FDG uptake observed in ALS patients. This finding reflects the selective activation of the ER-PPP in response to a significant redox stress associated with alterations of mitochondrial ultrastructure, networking and connection with the ER itself. This scenario is less severe in cardiomyocytes suggesting a relevant role for either communication with synaptic plaque or contraction dynamics.
Evaluation of ESBL (Extended Spectrum Beta-Lactamase) Producing Escherichia Coli Isolated from Patients with Urinary Tract Infection by Phenotypic and Genotypic Methods
Authors: Namaei Mohammad Hasan , Hamzei Hengameh , Moghanni Marzie , Ebrahimzadeh Azadeh
Published: April 2020

Background: Urinary Tract Infection (UTI) is the most common bacterial infection in the world. E. coli is the predominant Pathogen. This study evaluates the prevalence of ESBL in E. colis isolated from patients with urinary tract infections with phenotypic and genotypic methods.Methods: This descriptive-analytical study was done on 155 isolates of E. coli isolated from patients with urinary tract infection who had received the study consent. After accurate identification of E. coli strains. ESBL production for Escherichia coli isolates which are resistant to ceftriaxone or ceftazidime was evaluated by CDT method. TEM, SHV and CTX-M genes were identified by PCR.Results: The results showed that 30 strains from 155 strains of E. coli had ESBL. Strains of ESBL producer were more in males was lower in educated persons. 38.9% of ESBL producer had antibiotic use, 29.9% -producing Escherichia hospitalization and 31.6% uti history. The highest level of drug allergy in the ESBL was related to nitrofurantoin, and the highest resistance was related to cefazolin, co-trimoxazole. The CTX-M and the CTX-M15 gene were found in 92.7% and 57.1% of cases, respectively; also the SHV and TEM genes were not found in any of ESBL-producing Escherichia coli strains. Most therapeutic response in patients was related to cefexime, ciprofloxacin and nitrofurantoin 27.4%, 26% 21.9%, respectively.Conclusion: This study showed that the history of antibiotic use, hospitalization, uti related to increase of ESBL-producing in E. coli isolates., the CTMX-M gene is the most common gene in ESBL-producing E. coli strains.
Arthroscopic superior capsule reconstruction using autologous fascia lata and biceps tendon augmentation
Authors: Hsu Chen-Heng , Chiu Chih-Hao , Weng Chun-Jui , Hsu Kuo-Yau , Chan Yi-Sheng , Chen Alvin Chao-Yu
Published: April 2020

Background: While arthroscopic superior capsule reconstruction (SCR) has been recently introduced to treat irreparable rotator cuff tear with encouraging outcomes, graft options and fixation remain debated. The purpose of this article is to describe a novel technique and present preliminary results in using long head of biceps tendon (LHBT) as augmentation for SCR with fascia lata autograft.Methods: Retrospective analysis was performed on 18 patients undergoing arthroscopic SCR with LHBT augmentation for irreparable rotator cuff tear between October 2017 and November 2019. Preoperative radiographic survey confirmed massive rotator cuff tear with moderate to severe muscle fatty infiltration and availability of LHBT. Fascia lata autograft harvested from ipsilateral thigh was folded and securely sutured. The folded fascia graft was then introduced through standard anterolateral portal and fixed to superior glenoid superiorly and greater tuberosity laterally with suture anchors. Anteriorly, fascia lata graft was sutured with proximal portion of LHBT instead of subscapularis tendon. A full coverage of rotator cuff defect by facial graft was then confirmed arthroscopically to allow tension-free suturing between posterior margin of fascia graft and residual infraspinatus tendon. Postoperative abduction brace and regular follow-up was arranged.Results: Being intact in 4 patients and either partially torn or subluxed in 14 patients, LHBT in all 18 patients were available for augmentation surgery. Preliminary functional survey revealed encouraging outcomes with a mean follow-up of 11.5 months. Nine patients with more than one year follow-up regained full forward elevation; ASES improved from 24.3 to 90.2. Acromiohumeral distance improved from 3.3 mm to 8.6 mm with radiographic analysis in those 9 patients.Conclusions: Arthroscopically LHBT augmented SCR is a novel technique and can be one of feasible opinions for irreparable rotator cuff tear.
The Physical Activity Wearables in the Police Force (PAW-Force) study: Acceptability and impact
Authors: Buckingham Sarah Ann , Morrissey Karyn , Williams Andrew James , Price Lisa , Harrison John
Published: April 2020

Background: Policing is a highly stressful and increasingly sedentary occupation. The study aim was to assess the acceptability and impact of a mobile health (mHealth) technology intervention (Fitbit® activity monitor and ‘Bupa Boost’ smartphone app) to promote physical activity (PA), reduce sedentary time, and improve health and wellbeing, perceived stress and perceived productivity in the police force.Methods: Single-group, pre-post, mixed methods pilot study. Police officers and staff (n=180) were recruited from two police forces in South West England. Participants used the technology for 12 weeks (an ‘individual’ then ‘social’ phase) followed by five months of optional use. Data sources included Fitbit®-recorded objective step count, questionnaire surveys and semi-structured interviews (n=32). Outcome assessment points were baseline (week 0), mid-intervention (week 6), post-intervention (week 12) and follow-up (month 8). Paired t-tests were used to investigate changes in quantitative outcomes. Qualitative analysis involved framework and thematic analysis.Results: Engagement with and perceived acceptability of the intervention was high overall, but a small number of participants reported negative physical (skin irritation) and psychological (feelings of guilt and anxiety) consequences of technology use. Changes in mean daily step count were non-significant (p>0.05), but self-reported PA increased in the short term (e.g. +465.4 MET-minutes/week total PA baseline to week 12, p=0.011) and longer term (e.g. +420.5 MET-minutes/week moderate-to-vigorous PA baseline to month 8, p=0.024). The greatest impact on behaviour was perceived by less active officers and staff. Individual app features (such as goal-setting and self-monitoring) were generally preferred to social components (social comparison, competitions and support). There were no significant changes in sedentary time; the findings highlighted the importance of context and external influences on behaviour. From baseline to month 8, there was a significant improvement in mental health-related quality of life (SF-12 mental component score +1.75 points, p=0.020). Despite interview-reported improvements in health and wellbeing, survey-assessed changes in physical health-related quality of life, perceived stress and perceived productivity were non-significant.Conclusions: mHealth technology is an acceptable and potentially impactful intervention for increasing PA in the police force. The intervention was less useful for reducing sedentary time and the impact on secondary outcomes is unclear.Trial registration: Registered with ClinicalTrials.gov on 30th May 2017 – retrospectively registered*. Registration number: NCT03169179, URL: https://clinicaltrials.gov/ct2/show/NCT03169179.
Phase II Multicenter Randomized Controlled Clinical Trial on the Efficacy of Intra-articular Injection of Autologous Bone Marrow Mesenchymal Stem Cells with Platelet Rich Plasma for the Treatment of Knee Osteoarthritis
Authors: Lamo-Espinosa José María , Blanco Juan F. , Sánchez Mikel , Moreno Victoria , Granero-Moltó Froilán , Sánchez-Guijo Fermín , Crespo-Cullel Íñigo , Mora Gonzalo , Vicente Diego Delgado San , Pompei-Fernández Orlando , Aquerreta Jesús Dámaso , Núñez-Córdoba Jorge María , Vitoria María , Valentí-Azcárate Andrés , Andreu Enrique J. , Cañizo María del Consuelo del , Valentí-Nin Juan Ramón , Prósper Felipe
Published: April 2020

Background
Mesenchymal stromal cells are a safe and promising option to treat knee osteoarthritis as previously demonstrated in different clinical trials. However, their efficacy, optimal dose and addition of adjuvants must be determined. Here, we evaluated the clinical effects of a dose of 100 × 106 bone marrow mesenchymal stromal cells (BM-MSCs) in combination with Platelet Rich Plasma (PRGF®) as adjuvant in a randomized clinical trial.
Methods
A phase II, multicenter, randomized clinical trial with active control was conducted. Sixty patients diagnosed with knee OA were randomly assigned to 3 weekly doses of PRGF® or intraarticular administration of 100 × 106 cultured autologous BM-MSCs plus PRGF®. Patients were followed up for 12 months, and pain and function were assessed using VAS and WOMAC and by measuring the knee range of motion range. X-ray and magnetic resonance imaging analyses were performed to analyze joint damage.
Results
No adverse effects were reported after BM-MSC administration or during follow-up. According to VAS, the mean value (SD) for PRGF® and BM-MSC with PRGF® went from 5 (1.8) to 4.5 (2.2) (p = 0.389) and from 5.3 (1.9) to 3.5 (2.5) (p = 0.01), respectively at 12 months.. In WOMAC, the mean (SD) baseline and 12-month overall WOMAC scores in patients treated with PRGF® was 31.9 (16.2) and 22.3 (15.8) respectively (p = 0.002) while that for patients treated with BM-MSC plus PRGF® was 33.4 (18.7) and 23.0 (16.6) (p = 0.053). Although between groups statistically significances have been not detected, only patients being treated with BM-MSC plus PRGF® could be considered as a OA treatment responders following OARSI criteria. X-ray and MRI (WORMS protocol) revealed no changes in knee joint space width or joint damage.
Conclusions
Treatment with BM-MSC associated with PRGF® was shown to be a viable therapeutic option for osteoarthritis of the knee, with clinical improvement at the end of follow-up. Further phase III clinical trials would be necessary to confirm the efficacy.
Comparison of COVID-19 Patterns Between Severely-Struck Italy and the Rest of the Worlds: An Observational Study
Authors: Jen Tung-Hui , Kan Wei-Chih , Yeh Yu-Tsen , Lin Jui-Chung John , Chien Tsair-Wei
Published: April 2020

Background The country of Italy was placed on lockdown when the number of cases of COVID-19 increased exponentially. It is of great concern which countries/regions would have the most similar patterns to Italy and the comparison of patterns, assuming homogeneity of variance within datasets, among regions worldwide, became necessary. There were no results in past literature regarding the identification of COVID-19 patterns among countries/regions. We were therefore motivated to propose an appropriate mathematic method, using a specific country/region (e.g., Italy), for example, in detecting similar patterns at the respective peak of the outbreak. A visual display highlighting COVID-19 patterns was proposed in this study using vector mathematics.Methods We downloaded COVID-19 outbreak numbers with confirmed cases in countries/regions on a daily basis from the Github website. The top peak point was identified for each country/region. Next, thirteen-time points were assigned before and after the inflection point. COVID-19 patterns were assessed by inspecting both similarity and distance using angle(or cosine theta in trigonometric function) and Chi-square statistics. Two sets of data on confirmed cases, one based on cases per 100,000 population and the other does not, were compared using rankings as well as four quadrants divided by similarity and distance. An app was developed to display regions with similar COVID-19 patterns to the selected country.Results The top four countries presenting with the most similar COVID-19 patterns to Italy were Switzerland, Norway, Iceland, and Luxembourg with Chi-square statistics per one freedom degree at 0.12, 0.37, 0.58, and 0.80, respectively, based on a population of 100,000. Visualizations with four quadrants and world map were shown on Google Maps. Rank correlation in rankings was − 0.03 between two sets of confirmed cases with and without using the basis of cases per population of 100,000.Conclusion We proposed and demonstrated a method using both criteria of similarity and distance from vectors in mathematics to identify countries that are most similar to Italy in terms of the pattern at the peak of the outbreak. The app was developed to display countries/regions with the most similar COVID-19 patterns to the targeted country/region using a dashboard laid on Google Maps. This method can be generalized and applied to study other countries/regions for the current pandemic and other past infectious disease in history.
Research on COVID-19 prevention and control strategies, and the effect of home quarantine in Shenzhen, China, 2020
Authors: Author) Zi-Qian Xu(Co-first , Author)) Jing-Zhong Wang(Co-first , Wang Hai-Rui , He Jian-Fan , Wang Bing , Yang Yong-Cun , Xian Hui-Xia , Zhang Ya-De , Feng Si-Yang , Li Min-Min , Song Li-Xia , Author) Xuan Zou(Co-corresponding , Author) Jian-Hua Lu(Co-corresponding
Published: April 2020

AbstractBackground: To study the prevention and control strategies of coronavirus disease 2019 (COVID-19), and to analyze the infection of the home-quarantined individuals with epidemic histories (came from Hubei and any other affected regions), but without symptoms in the three incubations after Wuhan closure in Shenzhen.Methods: The sample size was 2,004 individuals based on multistage sampling during the pre-investigation. Based on the results of the pre-investigation, the formal investigation expanded the sample size to 57,012 individuals. A single throat swab was collected from each individual for nucleic acid testing (NAT) by reverse transcription-polymerase chain reaction (RT-PCR). NAT was performed by a third-party institution, BGI. We collected information related to demographics, disease history, travel history, and personal protective measures before home quarantine, and monitored close-contact histories using the We Chat questionnaire.Results: The total infection rate of home-quarantined individuals was 0.11% (95% CI: 0.05%–0.24%) out of the total sample size of 59,016. The detection period for seven confirmed cases was primarily concentrated between February 8 and 18, 2020, which was during the second incubation period after Wuhan's closure. The home quarantined individuals with epidemic histories (came from Hubei and any other affected regions) were considered the high risk population during the first two incubations after Wuhan’s closure. No positive cases were detected from February 25 to present (the third incubation after Wuhan’s closure). The number of newly-confirmed cases per day was 0 for 8 days from February 22 to 29 in Shenzhen. Thus, the strategies of prevention and control were effective.Conclusions: The strategies and policies were effective for the prevention and control of COVID-19. Additionally, the strategy of implementing NAT during the first two incubations for home-quarantined individuals with epidemic histories (came from Hubei and any other affected regions), but without symptoms, facilitated early detection, early reporting, early diagnosis, early quarantining, and early treatment. However, our findings do not support NAT for home quarantined persons during the third incubation after Wuhan’s closure to present.
Burden of stigma among tuberculosis patients in a pastoralist community in Kenya: A mixed methods study.
Authors: Mbuthia Grace Wambura , Nyamogoba Henry DN , Chiang Silvia S. , McGarvey Stephen T
Published: April 2020

Background

Tuberculosis (TB) stigma remains a barrier to early diagnosis and treatment completion. Increased understanding of stigma is necessary for improved interventions to minimise TB stigma and its effects. The purpose of this study is to quantitatively measure TB stigma and to explore its manifestation among TB patients in a rural Kenyan community.
Methods

This was a hospital based study using explanatory sequential mixed methods approach. In the quantitative study, a questionnaire containing socio-demographic characteristics and scales measuring perceived TB stigma and experienced TB stigma, was administered to 208 adult pulmonary TB patients receiving treatment in West Pokot County. The qualitative data were collected through 15 in-depth interviews and 6 focus group discussions with TB patients. Descriptive and bivariate analysis was done for the quantitative data while the thematic analysis was done for qualitative data.
Results

The internal consistency reliability coefficients were satisfactory with Cronbach alphas of 0.87 and 0.86 for the 11-item and 12-item stigma measurement scale. The investigation revealed that TB stigma was high. TB stigma was exemplified through patients being isolated by others, self-isolation, fear to disclose TB diagnosis, association of TB with HIV and lack of social support. Being a woman was significantly associated with high levels of both experienced stigma (p = 0.007) and perceived stigma (p = 0.005) while age, marital status, occupation and the patient’s religion were not.
Conclusion

There is a need to implement stigma reduction interventions in order to improve TB program outcomes.