bluuebunny/crossref_metadata_2025 huggingface dataset:
The protective effect of cannabinoid type II receptor agonist AM1241 on ConA-induced liver injury in mice via mitogen-activated protein kinase signalling pathway
Authors: Wu Yafeng , Ma Run , Long Cuizhen , Shu Yuanhui , He Ping , Zhou Yan , Xiang Yining , Wang Yuping
Published: August 2021

Introduction

The endocannabinoid system plays an important role in regulating the immune responses in inflammation. At present, there are no good clinical drugs for many immune liver diseases.

Methods

We explored the protective effect of the cannabinoid type II (CB2) receptor agonist AM1241 on the liver of mice with acute liver injury caused by concanavalin from the perspective of inflammation and immunity. Pathological evaluation in hepatic tissue was examined by haematoxylin and eosin (HE) staining and the levels of biochemical parameters in the serum were measured by automatic biochemical analysis. The content of inflammatory factors was measured by enzyme-linked immunosorbent assay and real-time quantitative reverse transcription polymerase chain reaction (real-time PCR). The liver apoptosis-related proteins were observed by immunohistochemistry. The expression of liver injury-related proteins was analysed by Western blot. Immune cells were isolated from the liver of mice and studied in vitro.

Results

Reduced levels of alanine transaminase and aspartate transaminase were observed in ConA-induced liver injury mice treated with AM1241, together with attenuated liver damage evidenced by H&E staining. Moreover, AM1241 inhibited the protein and gene expression levels of TNF-α, IL-6 and IFN-γ in the livers of mice. The phosphorylation levels of p38, JNK, ERK1/2, P65 and cAMP response element-binding protein (CREB) in the mouse were significantly reduced in AM1241 pretreatment, while the level of p-JNK increased. In addition, the P/T-P65 and P/T-CREB of the AM1241 pretreatment group were significantly reduced. The results of immunohistochemistry measurement are consistent with those of Western blotting. The CB2-mediated effect is through macrophage-like Kupffer cells.

Conclusion

Our study suggests that the ConA-induced liver injury model in mice is protected by CB2 agonist AM1241 by modulation of CB2 receptor-rich immune cells, for example, Kupffer cells. Reduced inflammatory responses regulate apoptosis/cell death in the liver particularly hepatocytes and other parenchymal cells.
Chicoric acid alleviates LPS-induced inflammatory response through miR-130a-3p/IGF-1pathway in human lung A549 epithelial cells
Authors: Yan Zheng , Huang Qing-Lan , Chen Jun , Liu Fan , Wei Yi , Chen Shu-Li , Wu Chun-Yan , Li Zhen , Lin Xiao-Ping
Published: August 2021

To investigate the effects and potential mechanisms of chicoric acid (CA) on LPS-induced inflammatory response in A549 cells. 0–800 μM CA was added to A549 cells to determine the toxicity of CA using MTT assay. Then, 2 μg/mL LPS and 50 μM CA were simultaneously added to A549 cells to investigate the effects of CA. In order to investigate the effects of miR-130a-3p and IGF-1 on LPS-induced A549 cells, cells were infected with inhibitor of miR-130a-3p and si RNA IGF-1. The levels of inflammatory cytokines such as IL-1β, IL-6, and TNF-α were measured by real-time RT-PCR and enzyme-linked immunosorbent (ELISA) assay. The IGF-1 pathway and NF-κB expression were measured using immunoblot assay. Moreover, a luciferase activity assay was used to indicate the binding site of miR-130a-3p on the 3′UTR of IGF-1. 0–50 μM CA had no toxicity on A549 cells. Thus, we chose 50 μM CA for the following study. CA attenuated the inflammatory response by LPS through decreasing IL-1β, IL-6, and TNF-α levels and increasing IGF-1/IGF-1R expression. Inhibition of miR-130a-3p reduced the inflammatory response and restored IGF-1/IGF-1R pathway induced by LPS. Furthermore, luciferase activity results indicated that miR-130a-3p directly targeted IGF-1 to regulate inflammatory response. CA alleviates LPS-induced inflammatory response through miR-130a-3p/IGF-1pathway in A549 cells.
Higher Charlson Comorbidity Index Increases 90-Day Readmission Rate with Poorer Functional Outcomes in Surgically Treated Hip Fracture Patients
Authors: Gatot Cheryl , Shern-En Tan Evan , Liow Ming Han Lincoln , Yongqiang Chen Jerry , Png Meng Ai , Tan Mann Hong , Howe Tet Sen , Bee Koh Joyce Suang
Published: August 2021

Introduction

The associated mortality and morbidity in hip fracture patients pose a major healthcare burden for ageing populations worldwide. We aim to analyse how an individual’s comorbidity profile based on age-adjusted Charlson Comorbidity Index (CCI) may impact on functional outcomes and 90-day readmission rates after hip fracture surgery.

Materials and Methods

Surgically treated hip fracture patients between 2013 and 2016 were followed up for 1-year and assessed using Parker Mobility Score (PMS), EuroQol-5D (EQ-5D) and Physical and Mental Component Scores (PCS and MCS, respectively) of Short Form-36 (SF-36). Statistical analysis was done by categorising 444 patients into three groups based on their CCI: (1) CCI 0–3, (2) CCI 4–5 and (3) CCI ≥ 6.

Results

PMS, EQ-5D and SF-36 PCS were significantly different amongst the CCI groups pre-operatively and post-operatively at 3, 6 and 12 months (all P < 0.05), with CCI ≥ 6 predicting for poorer outcomes. In terms of 90-day readmission rates, patients who have been readmitted have poorer outcome scores. Multivariate analysis showed that high CCI scores and 90-day readmission rate both remained independent predictors of worse outcomes for SF-36 PCS, PMS and EQ-5D.

Discussion

CCI scores ≥6 predict for higher 90-day readmission rates, poorer quality of life and show poor potential for functional recovery 1-year post-operation in hip fracture patients. 90-day readmission rates are also independently associated with poorer functional outcomes. Peri-operatively, surgical teams should liaise with medical specialists to optimise patients’ comorbidities and ensure their comorbidities remain well managed beyond hospital discharge to reduce readmission rates. With earlier identification of patient groups at risk of poorer functional outcomes, more planning can be directed towards appropriate management and subsequent rehabilitation.

Conclusion

Further research should focus on development of a stratified, peri-operative multidisciplinary, hip-fracture care pathway treatment regime based on CCI scores to determine its effectiveness in improving functional outcomes.
Augmentation of Primary ACL Reconstruction With a Modified Ellison Lateral Extra-articular Tenodesis in High-Risk Patients: A Pilot Study
Authors: Feller Julian A. , Devitt Brian M. , Webster Kate E. , Klemm Haydn J.
Published: August 2021

Background:

Lateral extra-articular tenodesis (LET) has been used to augment primary anterior cruciate ligament (ACL) reconstruction to reduce the risk of reinjury. Most LET procedures result in a construct that is fixed to both the femur and the tibia. In a modified Ellison procedure, the construct is only fixed distally, reducing the risk of inadvertently overconstraining the lateral compartment.

Purpose:

To evaluate the use of the modified Ellison procedure in a cohort of patients deemed to be at a high risk of further ACL injury after primary ACL reconstruction.

Study Design:

Case series; Level of evidence, 4.

Methods:

Included were 25 consecutive patients with at least 2 of the following risk factors: age <20 years at the time of surgery, previous contralateral ACL reconstruction, positive family history of ACL rupture (parent or sibling), generalized ligamentous laxity (Beighton ≥4), grade 3 pivot shift in the consulting room, a desire to return to a pivoting sport, and an elite or professional status. All patients underwent primary ACL reconstruction with an additional modified Ellison procedure. Postoperatively, patients completed the IKDC subjective knee evaluation form (International Knee Documentation Committee), KOOS Quality of Life subscale (Knee injury and Osteoarthritis Outcome Score), ACL–Return to Sport After Injury Scale, Marx Activity Rating Scale, and SANE score (Single Assessment Numeric Evaluation).

Results:

At 12-month follow-up, the mean outcome scores were as follows: SANE, 94/100; IKDC, 92/100; Marx, 13/16; ACL–Return to Sport, 85/100; and KOOS, 77/100. At 24 months, return-to-sport data were available for 23 of 25 patients; 17 (74%) were playing at the same level or higher than preinjury and 2 at a lower level. One patient (4%) sustained a contact mechanism graft rupture at 12 months. There were 2 (9%) contralateral ACL injuries, including 1 ACL graft rupture, at 11 and 22 months postoperatively. There was a further contralateral ACL graft rupture at 26 months.

Conclusion:

The use of the modified Ellison procedure as a LET augmentation of a primary ACL reconstruction to produce a low graft rupture rate appeared to be safe in a cohort considered to be at a high risk of reinjury. The procedure showed promise in terms of reducing further graft injuries.
Effects of 7-day supplementation with escalating doses of citrulline nitrate on resting and post-exercise blood pressure and safety biomarkers in healthy men: A randomized controlled trial
Authors: Todorovic Nikola , Stajer Valdemar , Ratgeber Laszlo , Betlehem Jozsef , Acs Pongras , Ostojic Sergej M
Published: August 2021

We investigated the effects of 7-day supplementation with three different dosages of citrulline nitrate (CN) on blood pressure at rest and after exercise, biochemical safety markers, and self-reported outcome measures of adverse events in healthy men. 12 apparently healthy young men (age 25.9 ± 4.0 years; weight 78.6 ± 10.0 kg, height 181.0 ± 7.0 cm) volunteered to participate in this double-blind, randomized, placebo-controlled cross-over trial. The dosages of CN were 1.5 g per day (low dose), 3.0 g per day (medium dose), and 6.0 g per day (high dose). No significant differences were found for systolic and diastolic blood pressure and heart rate at rest and after exercise between varying doses of CN and placebo ( p > 0.05). In addition, hematological indices, biochemical variables, and clinical enzyme profiles were not affected by either intervention ( p > 0.05), and the type and frequency of side effects were comparable to the placebo group. Citrulline nitrate was safe and well tolerated when administered for 7 days in dosages up to 6 g per day.
Climate Change and Trade Facilitation: Estimating Greenhouse Gas Emission Savings from Implementation of Cross-Border Paperless Trade in Asia and the Pacific
Authors: Duval Yann , Hardy Simon
Published: August 2021

The Framework Agreement on Facilitation of Cross-Border Paperless Trade in Asia and the Pacific entered into force in February 2021. While economic benefits associated with paperless trade facilitation are well known, little attention has been paid to measuring the potential environmental benefits. Accordingly, this article sets out to quantify the amount of greenhouse gas emissions that could be saved if all trade-related paper documents in the region are ultimately replaced by digital documents and data exchange, as foreseen in the regional framework agreement. This is carried out by combining detailed descriptions of trade transactions, data on trading volumes and relevant emission factors. Even with conservative assumptions, the emissions saved by fully digitalising a single end-to-end trade transaction are equivalent to planting 1.5 trees. For the Asia-Pacific, this implies savings of about 13 million tons of CO2e annually, equivalent to the carbon absorbed by 400 million trees. The results are driven by efficiency gains from handling data digitally rather than by the direct savings of paper and ink.

JEL Codes: F18, H83, Q56
NGA-subduction global ground motion models with regional adjustment factors
Authors: Parker Grace A , Stewart Jonathan P , Boore David M , Atkinson Gail M , Hassani Behzad
Published: August 2021

We develop semi-empirical ground motion models (GMMs) for peak ground acceleration, peak ground velocity, and 5%-damped pseudo-spectral accelerations for periods from 0.01 to 10 s, for the median orientation-independent horizontal component of subduction earthquake ground motion. The GMMs are applicable to interface and intraslab subduction earthquakes in Japan, Taiwan, Mexico, Central America, South America, Alaska, the Aleutian Islands, and Cascadia. The GMMs are developed using a combination of data inspection, data regression with respect to physics-informed functions, ground-motion simulations, and geometrical constraints for certain model components. The GMMs capture observed differences in source and path effects for interface and intraslab events, conditioned on moment magnitude, rupture distance, and hypocentral depth. Site effect and aleatory variability models are shared between event types. Regionalized GMM components include the model constant (that controls ground motion amplitude), anelastic attenuation, magnitude-scaling break point, linear site response, and sediment depth terms. We develop models for the aleatory between-event variability [Formula: see text], within-event variability [Formula: see text], single-station within-event variability [Formula: see text], and site-to-site variability [Formula: see text]. Ergodic analyses should use the median GMM and aleatory variability computed using the between-event and within-event variability models. An analysis incorporating non-ergodic site response should use the median GMM at the reference shear-wave velocity condition, a site-specific site response model, and aleatory variability computed using the between-event and single-station within-event variability models. Epistemic uncertainty in the median model is represented by standard deviations on the regional model constants, which facilitates scaled-backbone representations of model uncertainty in hazard analyses.
Lung Ultrasonography in Ruling Out COVID-19 Among Health Care Workers in Two Italian Emergency Departments: A Multicenter Study
Authors: Copetti Roberto , Amore Giulia , Giudice Caterina Anna , Orso Daniele , Cola Silvia , Pillinini Pierpaolo , Rocco Chiara , Cappello Dario , Dibenedetto Alessia Geneve , Meduri Stefano
Published: August 2021

Objective:

The low sensitivity of the real-time reverse transcription-polymerase chain reaction (rRT-PCR) test on the nasopharyngeal swab for SARS-CoV2 virus could cause infections among health care professionals and could be a source of viral spread. The aim of this study was to verify whether lung ultrasonography (LUS) had a negative predictive value (NPV) high enough to rule out coronavirus disease 2019 (COVID-19) in a cohort of health care employees, working in emergency departments (EDs).

Materials and Methods:

A multicenter prospective observational study was conducted in two EDs in Northeast Italy. An adjudication committee established the definitive diagnosis of COVID-19.

Results:

A cohort was enrolled of 155 possible patient cases (two true positives). Twenty-one health care employees presented with suggestive symptoms for COVID-19. The rRT-PCR test was positive in one of the two patients. LUS was suggestive for COVID-19 pneumonia in four patients. The diagnostic accuracy of LUS was 98.7% (95% confidence interval [CI] = 95.4%–99.8%). The NPV was 100% (95% CI = 100%–100%).

Conclusion:

LUS has a high enough NPV for excluding a COVID-19-related pneumonia in a cohort of health care employees who were exposed to the SARS-CoV2 virus.
Excess heme upregulates heme oxygenase 1 and promotes cardiac ferroptosis in mice with sickle cell disease
Authors: Menon Archita Venugopal , Liu Jing , Tsai Hanting Phoebe , Zeng Lingxue , Yang Seungjeong , Asnani Aarti , Kim Jonghan
Published: August 2021

Sickle cell disease (SCD) is characterized by increased hemolysis, which results in plasma heme overload and ultimately cardiovascular complications. Here, we hypothesized that increased heme in SCD causes upregulation of heme oxygenase 1 (Hmox1), which consequently drives cardiomyopathy through ferroptosis, an iron-dependent non-apoptotic form of cell death. First, we demonstrated that the Townes SCD mice had higher levels of hemopexin-free heme in the serum and increased cardiomyopathy, which was corrected by hemopexin supplementation. Cardiomyopathy in SCD mice was associated with upregulation of cardiac Hmox1, and inhibition or induction of Hmox1 improved or worsened cardiac damage, respectively. Because free iron, a product of heme degradation through Hmox1, has been implicated in toxicities including ferroptosis, we evaluated the downstream effects of elevated heme in SCD. Consistent with Hmox1 upregulation and iron overload, levels of lipid peroxidation and ferroptotic markers increased in SCD mice, which were corrected by hemopexin administration. Moreover, ferroptosis inhibitors decreased cardiomyopathy, whereas a ferroptosis inducer erastin exacerbated cardiac damage in SCD and induced cardiac ferroptosis in nonsickling mice. Finally, inhibition or induction of Hmox1 decreased or increased cardiac ferroptosis in SCD mice, respectively. Together, our results identify ferroptosis as a key mechanism of cardiomyopathy in SCD.
Whole-brain morphological alterations associated with trigeminal neuralgia
Authors: Mo Jiajie , Zhang Jianguo , Hu Wenhan , Luo Fang , Zhang Kai
Published: August 2021

Background

Novel neuroimaging strategies have the potential to offer new insights into the mechanistic basis for trigeminal neuralgia (TN). The present study aims to conduct whole-brain morphometry analyses of TN patients and to assess the value of group-level neocortical and subcortical structural patterns as tools for diagnostic biomarker exploration.

Methods

Cortical thickness, surface area, and myelin levels in the neocortex were measured via magnetic resonance imaging (MRI). The radial distance and the Jacobian determinant of the subcortex in 43 TN patients and 43 matched controls were compared. Pattern learning algorithms were employed to establish the utility of group-level MRI findings as tools for predicting TN. An additional 40 control patients with hemifacial spasms were then evaluated to assess algorithm sensitivity and specificity.

Results

TN patients exhibited reductions in cortical indices in the anterior cingulate cortex (ACC), the midcingulate cortex (MCC), and the posterior cingulate cortex (PCC) relative to controls. They further presented with widespread subcortical volume reduction that was most evident in the putamen, the thalamus, the accumbens, the pallidum, and the hippocampus. Whole brain-level morphological alterations successfully enable automated TN diagnosis with high specificity (TN: 95.35 %; disease controls: 46.51 %).

Conclusions

TN is associated with a distinctive whole-brain structural neuroimaging pattern, underscoring the value of machine learning as an approach to differentiating between morphological phenotypes, ultimately revealing the full spectrum of this disease and highlighting relevant diagnostic biomarkers.
OVarFlow: a resource optimized GATK 4 based Open source Variant calling workFlow
Authors: Bathke Jochen , Lühken Gesine
Published: August 2021

Background

The advent of next generation sequencing has opened new avenues for basic and applied research. One application is the discovery of sequence variants causative of a phenotypic trait or a disease pathology. The computational task of detecting and annotating sequence differences of a target dataset between a reference genome is known as "variant calling". Typically, this task is computationally involved, often combining a complex chain of linked software tools. A major player in this field is the Genome Analysis Toolkit (GATK). The "GATK Best Practices" is a commonly referred recipe for variant calling. However, current computational recommendations on variant calling predominantly focus on human sequencing data and ignore ever-changing demands of high-throughput sequencing developments. Furthermore, frequent updates to such recommendations are counterintuitive to the goal of offering a standard workflow and hamper reproducibility over time.

Results

A workflow for automated detection of single nucleotide polymorphisms and insertion-deletions offers a wide range of applications in sequence annotation of model and non-model organisms. The introduced workflow builds on the GATK Best Practices, while enabling reproducibility over time and offering an open, generalized computational architecture. The workflow achieves parallelized data evaluation and maximizes performance of individual computational tasks. Optimized Java garbage collection and heap size settings for the GATK applications SortSam, MarkDuplicates, HaplotypeCaller, and GatherVcfs effectively cut the overall analysis time in half.

Conclusions

The demand for variant calling, efficient computational processing, and standardized workflows is growing. The Open source Variant calling workFlow (OVarFlow) offers automation and reproducibility for a computationally optimized variant calling task. By reducing usage of computational resources, the workflow removes prior existing entry barriers to the variant calling field and enables standardized variant calling.
Integrated ionomic and transcriptomic dissection reveals the core transporter genes responsive to varying cadmium abundances in allotetraploid rapeseed
Authors: Zhou Ting , Yue Cai-peng , Zhang Tian-yu , Liu Ying , Huang Jin-yong , Hua Ying-peng
Published: August 2021

Background

Oilseed rape (B. napusL.) has great potential for phytoremediation of cadmium (Cd)-polluted soils due to its large plant biomass production and strong metal accumulation. Soil properties and the presence of other soluble compounds or ions, cause a heterogeneous distribution of Cd.

Results

The aim of our study was to reveal the differential responses ofB. napusto different Cd abundances. Herein, we found that high Cd (50 μM) severely inhibited the growth ofB. napus, which was not repressed by low Cd (0.50 μM) under hydroponic culture system. ICP-MS assays showed that the Cd2+concentrations in both shoots and roots under 50 μM Cd were over 10 times higher than those under 0.50 μM Cd. Under low Cd, the concentrations of only shoot Ca2+/Mn2+and root Mn2+were obviously changed (both reduced); under high Cd, the concentrations of most cations assayed were significantly altered in both shoots and roots except root Ca2+and Mg2+. High-throughput transcriptomic profiling revealed a total of 18,021 and 1408 differentially expressed genes under high Cd and low Cd conditions, respectively. The biological categories related to the biosynthesis of plant cell wall components and response to external stimulus were over-accumulated under low Cd, whereas the terms involving photosynthesis, nitrogen transport and response, and cellular metal ion homeostasis were highly enriched under high Cd. Differential expression of the transporters responsible for Cd uptake (NRAMPs), transport (IRTsandZIPs), sequestration (HMAs,ABCs, andCAXs), and detoxification (MTPs,PCR,MTs, andPCSs), and some other essential nutrient transporters were investigated, and gene co-expression network analysis revealed the core members of these Cd transporters. Some Cd transporter genes, especiallyNRAMPsandIRTs, showed opposite responsive patterns between high Cd and low Cd conditions.

Conclusions

Our findings would enrich our understanding of the interaction between essential nutrients and Cd, and might also provide suitable gene resources and important implications for the genetic improvement of plant Cd accumulation and resistance through molecular engineering of these core genes under varying Cd abundances in soils.
Loci and natural alleles for cadmium-mediated growth responses revealed by a genome wide association study and transcriptome analysis in rice
Authors: Yu Jianping , Liu Chaolei , Lin Hai , Zhang Bin , Li Xiaoxia , Yuan Qiaoling , Liu Tianjiao , He Huiying , Wei Zhaoran , Ding Shilin , Zhang Chao , Gao Hongsheng , Guo Longbiao , Wang Quan , Qian Qian , Shang Lianguang
Published: August 2021

Background

Cadmium (Cd) is a toxic heavy metal that is harmful to the environment and human health. Cd pollution threatens the cultivation of rice (Oryza sativaL.) in many countries. Improving rice performance under Cd stress could potentially improve rice productivity.

Results

In this study, 9 growth traits of 188 different cultivated rice accessions under normal and Cd stress conditions were found to be highly variable during the seedling stage. Based on ~3.3 million single nucleotide polymorphisms (SNPs), 119 Cd-mediated growth response (CGR) quantitative trait loci (QTL) were identified by a genome-wide association study (GWAS), 55 of which have been validated by previously reported QTL and 64 were new CGR loci. Combined with the data from the GWAS, transcriptome analysis, gene annotations from the gene ontology (GO) Slim database, and annotations and functions of homologous genes, 148 CGR candidate genes were obtained. Additionally, several reported genes have been found to play certain roles in CGRs. Seven Cd-related cloned genes were found among the CGR genes. Natural elite haplotypes/alleles in these genes that increased Cd tolerance were identified by a haplotype analysis of a diverse mini core collection. More importantly, this study was the first to uncover the natural variations of 5 GST genes that play important roles in CGRs.

Conclusion

The exploration of Cd-resistant rice germplasm resources and the identification of elite natural variations related to Cd-resistance will help improve the tolerance of current major rice varieties to Cd, as well as provide raw materials and new genes for breeding Cd-resistant varieties.
A timed activity protocol to address sleep-wake disorders in home dwelling persons living with dementia: the healthy patterns clinical trial
Authors: Hodgson Nancy A. , Gooneratne Nalaka , Perez Adriana , Talwar Sonia , Huang Liming
Published: August 2021

Background

Sleep-wake disorders occur in most persons living with dementia and include late afternoon or evening agitation, irregular sleep-wake rhythms such as daytime hypersomnia, frequent night awakenings, and poor sleep efficiency. Sleep-wake disorders pose a great burden to family caregivers, and are the principal causes of distress, poor quality of life, and institutionalization. Regulating the sleep-wake cycle through the use of light and activity has been shown to alter core clock processes and suggests that a combination of cognitive, physical, and sensory-based activities, delivered at strategic times, may be an effective mechanism through which to reduce sleep-wake disorders.

Methods

A definitive Phase III efficacy trial of the Healthy Patterns intervention, a home-based activity intervention designed to improve sleep-wake disorders and quality of life, is being conducted using a randomized two-group parallel design of 200 people living with dementia and their caregivers (dyads). Specific components of this one-month, home-based intervention involve 4 in-home visits and includes: 1) assessing individuals’ functional status and interests; 2) educating caregivers on environmental cues to promote activity and sleep; and 3) training caregivers in using timed morning, afternoon, and evening activities based on circadian needs across the day. The patient focused outcomes of interest are quality of life, measures of sleep assessed by objective and subjective indicators including actigraphy, subjective sleep quality, and the presence of neuropsychiatric symptoms. Caregiver outcomes of interest are quality of life, burden, confidence using activities, and sleep disruption. Salivary measures of cortisol and melatonin are collected to assess potential intervention mechanisms.

Discussion

The results from the ongoing study will provide fundamental new knowledge regarding the effects of timing activity participation based on diurnal needs and the mechanisms underlying timed interventions which can lead to a structured, replicable treatment protocol for use with this growing population of persons living with dementia.

Clinical trial registration

Clinicaltrials.gov# NCT03682185 athttps://clinicaltrials.gov/; Date of clinical trial registration: 24 September 2018.
Erythema induratum of Bazin as an indicative manifestation of cavitary tuberculosis in an adolescent: a case report
Authors: Yang Kun , Li Tingying , Zhu Xiaomei , Zou Yun , Liu Dongxian
Published: August 2021

Background

Erythema induratum of Bazin (EIB) is a rare cutaneous manifestation of tuberculosis (TB) that frequently occurs in middle-aged women. The clinical manifestations of EIB can mimic various skin diseases, easily leading to misdiagnosis or underdiagnosis. We report a case of a 16-year-old Chinese girl who initially presented with EIB and was subsequently diagnosed with cavitary TB.

Case presentation

The patient is a 16-year-old Chinese girl who presented with clusters of erythematous subcutaneous nodules on the posterior part of her right lower leg matching the clinical manifestations of EIB but was otherwise asymptomatic. The patient was subsequently diagnosed with cavitary TB on the basis of a positive result from a T-SPOT.TB test and the observation of cavitary lung lesions in chest computed tomography scanning. A good clinical response was observed in the patient after the initial phase of a standard 6-month antibiotic regimen.

Conclusions

Adolescents infected with Mycobacterium tuberculosis frequently present atypical symptoms. Cutaneous manifestations of tuberculosis in adolescents can be considered good clinical indicators to predict the underlying disease. Strong clinical suspicion is required for a prompt diagnosis in adolescents with EIB.
Association between CD4+ T cell counts and gut microbiota and serum cytokines levels in HIV-infected immunological non-responders
Authors: Lu Danfeng , Zhang Jian-Bo , Wang Yue-Xin , Geng Shi-Tao , Zhang Zunyue , Xu Yu , Li Shao-You , Wang Kun-Hua , Kuang Yi-Qun
Published: August 2021

Background

CD4+ T cell counts in certain human immunodeficiency virus (HIV)-infected patients called immunological non-responders (INRs) could not return to a normal level even with sustained antiretroviral therapy (ART) because of persistent immune activation, which is associated with pro-inflammatory cytokines production and an altered intestinal microbiome profile. Changes in gut bacterial composition have been linked to low CD4+ T cell counts in HIV-infected individuals. However, the association between CD4+ T cell counts and gut microbiota community composition and cytokines levels in INRs (CD4+ T cell counts < 500 cells/μL) from Yunnan Province, China, has not been previously investigated.

Methods

To address this issue, we carried out a cross-sectional study of 34 HIV-infected INRs. The patients were divided into CD4 count > 200 cells/μL group and CD4 count < 200 cells/μL group. The gut microbiota composition of each subject was analyzed by 16S rRNA gene sequencing. We also compared CD8+ T cell counts, pro-inflammatory cytokines levels, and nutritional status between the two groups.

Results

Compared to INRs with CD4 count > 200 cells/μL, those with CD4 count < 200 cells/μL had a lower CD4/CD8 ratio, lower nutritional status and higher serum levels of tumor necrosis factor (TNF)-α, interferon-γ-inducible protein (IP)-10 and interleukin (IL)-1α. Ruminococcaceae was less abundant in the CD4 count < 200 cells/μL group than in the CD4 count > 200 cells/μL group, and difference in alpha diversity was observed between the two groups. Moreover, CD4+ T cell counts were negatively associated with TNF-α and IL-1α levels and positively associated with the relative abundance of Ruminococcaceae.

Conclusions

Our study demonstrated that lower CD4+ T cell counts in INRs are associated with a reduced abundance of Ruminococcaceae in the gut and elevated serum pro-inflammatory cytokines levels. Thus, interventions targeting gut microbiota to increase CD4+ T cell counts are a potential strategy for promoting immune reconstitution in HIV-infected INRs.
Peripheral neuropathy in HIV-infected children attending care and treatment clinic, at Muhimbili National Hospital, Dar es Salaam: a cross sectional study
Authors: Amiji Insiyah A , Naburi Helga E , Kija Edward , Mumburi Livin P
Published: August 2021

Background

Peripheral neuropathy (PN) is a neurological complication of untreated Human Immunodeficiency Virus (HIV) infection or exposure to certain antiretroviral drugs. In Tanzania where HIV is a major public health problem, the burden of HIV associated peripheral neuropathy has not yet been well defined in children.Thisstudy investigated the prevalence and associated factors for peripheral neuropathy among children living with HIV, attending Care and Treatment Clinic (CTC) at Muhimbili National Hospital (MNH).

Materials and methods

A cross-sectional study was conducted among 383 HIV positive children aged 5 to 18 years at MNH, CTC in Dar es Salaam between October to December 2019. All participants provided written assent/consent. Structured questionnaires designed for this study was used to collect data and screening for peripheral neuropathy was done on each participant using the Pediatric modified Total Neuropathy Score (Ped m TNS) that includes subjective and objective assessment. A score of 5 or greater on the Ped m TNS was used to define peripheral neuropathy. Data analysis was done using SPSS Version 23.

Results

The prevalence of peripheral neuropathy among HIV infected children was 14.1 % (95 % CI (10.8 − 18 %). Common neuropathic symptoms were numbness, tingling sensation, reduced ankle reflexes and reduced sensation to light touch and pain that was limited to the toes. Low CD4 cell count (OR = 12.21; 95 % CI3.75–39.66; p = 0.0001), high viral load (OR = 10.54; 95 % CI 3.19–34.77; p = 0.0001), ART regime containing NRTI plus PI (OR = 3.93; 95 % CI 1.43– 10.74; p = 0.01) and the last exposure to isoniazid more than 6 months ago (OR = 3.71; 95 % CI 1.57–8.77; p = 0.003) were independent predictors for peripheral neuropathy.

Conclusion

Peripheral neuropathy is common among HIV infected children attending CTC at MNH and its frequency increases with advanced disease. The choice of ART regimen and other drugs for treating comorbid conditions should carefully be evaluated.
Performing central venous catheters in neonates and small infants undergoing cardiac surgery using a wireless transducer for ultrasound guidance: a prospective, observational pilot study
Authors: Schiefer Judith , Lichtenegger Paul , Zimpfer Daniel , Hutschala Doris , Kuessel Lorenz , Felli Alessia , Hornykewycz Stephan , Faybik Peter , Base Eva
Published: August 2021

Background

Neonates and small infants with congenital cardiac disease undergoing cardiac surgery represent major challenges facing paediatric anaesthesia and perioperative medicine. Aims.

We here aimed to investigate the success rates in performing ultrasound (US) guided central venous catheter insertion (CVC) in neonates and small infants undergoing cardiac surgery, and to evaluate the practicability and feasibility of thereby using a novel wireless US transducer (WUST).

Methods

Thirty neonates and small infants with a maximum body weight of 10 kg and need for CVC before cardiac surgery were included in this observational trial and were subdivided into two groups according to their weight: < 5 kg and ≥ 5 kg. Cannulation success, failure rate, essential procedure related time periods, and complications were recorded and the clinical utility of the WUST was assessed by a 5-point Likert scale.

Results

In total, CVC-insertion was successful in 27 (90%) of the patients and the first attempt was successful in 24 (78%) of patients. Success rates of CVC were 80% < 5 kg and 100% ≥5 kg. Comparing the two groups we found a clear trend towards longer needle insertion time in patients weighing < 5 kg (33 [28–69] vs. 24 [15–37]s, P = .07), whereas, the total time for catheter insertion and the duration of the whole procedure were similar in both groups (199 [167–228] vs. 178 [138–234] and 720[538–818] vs. 660 [562–833]s. In total, we report 3 (10%) cases of local hematoma as procedure-related complications. Assessments of the WUST revealed very good survey results for all parameters of practicability and handling (all ratings between 4.5 and 5.0).

Conclusion

Although difficulties in CVC-placement seem to relate to vessel size and patient’s weight, US guided CVC-insertion represents a valuable, fast, and safe intervention in neonates and small children undergoing cardiac surgery. Using the WUST is feasible for this clinical application and may aid in efforts aiming to optimize perioperative care.

Trial registration

Wireless US-guided CVC placement in infants; Clinicaltrials.gov: NCT04597021; Date of Registration: 21October, 2020; retrospectively registered.
Cost-effectiveness of a stepped care program to prevent depression among primary care patients with diabetes mellitus type 2 and/or coronary heart disease and subthreshold depression in comparison with usual care
Authors: van Dijk S. E. M. , Pols A. D. , Adriaanse M. C. , van Marwijk H. W. J. , van Tulder M. W. , Bosmans J. E.
Published: August 2021

Background

Patients with diabetes mellitus type 2 (DM2) and/or coronary heart disease (CHD) are at high risk to develop major depression. Preventing incident major depression may be an important tool in reducing the personal and societal burden of depression. The aim of the current study was to assess the cost-effectiveness of a stepped care program to prevent major depression (Step-Dep) in diabetes mellitus type 2 and/or coronary heart disease patients with subthreshold depression in comparison with usual care.

Methods

An economic evaluation with 12 months follow-up was conducted alongside a pragmatic cluster-randomized controlled trial from a societal perspective. Participants received care as usual (n = 140) or Step-Dep (n = 96) which consisted of four sequential treatment steps: watchful waiting, guided self-help, problem solving treatment and referral to a general practitioner. Primary outcomes were quality-adjusted life years (QALYs) and cumulative incidence of major depression. Costs were measured every 3 months. Missing data was imputed using multiple imputation. Uncertainty around cost-effectiveness outcomes was estimated using bootstrapping and presented in cost-effectiveness planes and acceptability curves.

Results

There were no significant differences in QALYs or depression incidence between treatment groups. Secondary care costs (mean difference €1644, 95% CI €344; €3370) and informal care costs (mean difference €1930, 95% CI €528; €4089) were significantly higher in the Step-Dep group than in the usual care group. The difference in total societal costs (€1001, 95% CI €-3975; €6409) was not statistically significant. The probability of the Step-Dep intervention being cost-effective was low, with a maximum of 0.41 at a ceiling ratio of €30,000 per QALY gained and 0.32 at a ceiling ratio of €0 per prevented case of major depression.

Conclusions

The Step-Dep intervention is not cost-effective compared to usual care in a population of patients with DM2/CHD and subthreshold depression. Therefore, widespread implementation cannot be recommended.

Trial registration

The trial was registered in the Netherlands Trial Register (NTR3715).
Dynamic monitor on psychological problems of medical aid teams in the context of corona virus disease 2019: a multi-stage and multi-factor quantitative study
Authors: Zhou Yanji , Li Chengyu , Zhang Xiyu , Xu Li , Li Yuze , Miao Wenqing , Dai Yingbo , You Dingyun , Li Ye
Published: August 2021

Background

To explore the psychological status and vulnerability characteristics of medical staff with the progress of the epidemic.

Methods

This study investigated the prevalence of mental problems of 2748 medical staff in four stages. The PHQ-9 (Patient Health Questionnaire), GAD-7 (Generalized Anxiety Disorder questionnaire), SSS (Somatization Symptom Checklist), Pittsburgh sleep quality index, and PCL-C (Self-rating scale for post-traumatic stress disorder) were used for the psychological evaluation, and univariate logistic standardised analysis, and multivariate logistic regression for data analysis.

Results

The prevalence of mental problems showed a statistically significant difference. In Stage 1, mild anxiety and mild depression reached the highest value of 41.4 and 40.72% respectively. Between 4 and 17 March that of mild depression rose from 16.07 to 26.7%, and between 17 and 26 March the prevalence of mild anxiety increased from 17.28 to 20.02%. Female, unmarried, and working in Wuhan are the risk factors of mental health of medical staff (P < 0.05).

Conclusion

The psychological status of the medical staff has changed dynamically. Stage 1 and the latter period of Stages 2 and 3 are the high-risk stages. Female and unmarried are the dangerous characteristics of psychological vulnerability.
Decision-making autonomy of women and other factors of anemia among married women in Ethiopia: a multilevel analysis of a countrywide survey
Authors: Tiruneh Fentanesh Nibret , Asres Degnet Teferi , Tenagashaw Mesfin Wogayehu , Assaye Hirut
Published: August 2021

Background

Anemia is one of the world’s public health problem, especially in developing nations. The majority of women of childbearing age (15–49) are affected by anemia. Women’s role in the decision-making process is significant for their health and related issues such as anemia. So far, there is no evidence of women’s decision-making autonomy on anemia. Consequently, this study aimed to robustly examine both individual- and group-level women’s decision-making autonomy and other determinants of anemia among married women in Ethiopia.

Methods

We examined data from an Ethiopian demographic and health survey conducted in 2016. Our analysis included 9220 married women of childbearing age (15–49 years). For bivariate analysis, we applied the chi-squared (X2) test. The relationship between individual and group-level women’s decision-making autonomy and anemia was assessed using multilevel binary logistic regression models while adjusting other socio-demographic and economic characteristics.

Results

In this study the magnitude of anemia was 30.5% (95% CI; 29.5–31.4). According to our multilevel analysis, group-level women’s autonomy was found to be negatively related with anemia than individual-level women’s autonomy (AOR = 0.53, 95% CI = 0.41–0.69). In addition, the indicator of women’s wealth index at group level was a protective factor (AOR = 0.68, 95% CI =0.51–0.90) to develop anemia. Among individual-level indicators women’s age (AOR = 0.73, 95% CI = 0.60–0.89), use of contraceptive (AOR = 0.66, 95% CI = 0.55–0.81), BMI (AOR = 0.71, 95% CI = 0.59–0.86) and employment status (AOR = 0.88, 95% CI = 0.79–0.98) were negatively related with anemia. While women who follow Muslim religion (AOR = 1.62, 95% CI = 1.32–1.97,), women who had five and above number of children (AOR = 93, 95% CI = 1.53–2.46), and who were pregnant (AOR = 1.21, 95% CI = 1.04–1.40) were positively associated with anemia.

Our final model showed that around 27% of the variability of having anemia was because of group-level differences (ICC = 0.27,P < 0.001). In addition, both individual and group-level factors account for 56.4% of the variance in the in the severity of anemia across communities (PCV = 56.4%).

Conclusions

Our study showed that empowering women within households is not only an important mechanism to reduce anemia among married women but also serves as a way to improve the lives of other women within the society.
The clinical and radiological characteristics of pulmonary cryptococcosis in immunocompetent and immunocompromised patients
Authors: Hu Yan , Ren Si-Ying , Xiao Peng , Yu Feng-Lei , Liu Wen-Liang
Published: August 2021

Background

We characterized the clinical features, radiographic characteristics, and response to treatment of immunocompetent and immunocompromised patients with pulmonary cryptococcosis (PC).

Methods

We retrospectively reviewed the medical records and radiological profiles of patients diagnosed with PC who received surgical resection between May 2015 and November 2020 in a tertiary referral center.

Results

A total of 21 males and 18 females were included in the study. 23 patients were immunocompetent and 20 out of the 39 were asymptomatic. Immunocompetent patients were diagnosed with PC at a younger age than immunocompromised patients (48.9 vs 57.1 years, P = 0.02). Single nodule pattern was the most frequent lesion pattern (33 out of 39, 84.6%) and right upper lobe was the most common site of location (15 out of 47, 31.9%). The majority of lesions were located peripherally (38 out of 47, 80.9%) and most lesions were 1–2 cm in diameter (30 out of 47, 63.8%). Cavitation was more likely to occur in immunocompromised patients (5 out of 11, 45.5%) than in immunocompetent patients (6 out of 36, 16.7%) (P = 0.04) and there was complete resolution of PC in all patients treated with anti-fungal therapy.

Conclusions

Immunocompetent patients were diagnosed with PC at a younger age than immunocompromised patients. Single nodule pattern was the most frequent lesion pattern in PC patients. Cavitation was more likely to occur in immunocompromised patients than in immunocompetent patients.
Flexible e-learning video approach to improve fundus examination skills for medical students: a mixed-methods study
Authors: Shikino Kiyoshi , Rosu Claudia A. , Yokokawa Daiki , Suzuki Shingo , Hirota Yusuke , Nishiya Katsumi , Ikusaka Masatomi
Published: August 2021

Background

Training for the fundus examination using traditional teaching is challenging, resulting in low generalist physicians’ confidence in performing the funduscopic examination. There is growing evidence suggesting a flexible e-learning video approach’s value in teaching physical examination procedures. However, whether the flexible e-learning video approach is superior to the traditional, face-to-face (F2F) lecture-based teaching for the funduscopic exam and the cognitive processes supporting its effectiveness has not yet been determined.

Methods

We conducted a sequential explanatory mixed-method study to compare the flexible e-learning video approach’s effectiveness versus the F2F lecture-based approach for teaching the funduscopic exam to medical students at Chiba University in Japan. Medical students were randomly assigned to either a flexible e-learning video approach group or a F2F lecture approach group. We then quantitatively measured the diagnostic accuracy of funduscopic findings before and after attending the specific classrooms. Next, we conducted student focus groups to explore the students’ thinking processes in the flexible e-learning video approach vs. the F2F lecture-based teaching of fundus examination. The qualitative data were analyzed using the qualitative content analysis method.

Results

The mean diagnostic accuracy scores in the post-test significantly increased from pre-test in the intervention group (36.6 to 63.4%,p < 0.001). Post-post comparisons across the two groups revealed a significant difference (intervention group 63.4% vs. control group 34.6%, p < 0.001). Six semi-structured focused group interviews were conducted (n = 36). In the flexible e-learning video approach group, we identified ten categories corresponding to four levels of the revised Bloom’s taxonomy: remember, understand, apply, analyze. Five categories were identified in the traditional F2F lecture approach group corresponding to three revised Bloom’s taxonomy levels: understand, apply, analyze. Interrater reliability was substantial (Cohen’s kappa = 0.81).

Conclusions

Teaching medical students funduscopic examination using the flexible e-learning video approach leads to improved diagnostic accuracy of funduscopic examinations. The flexible e-learning video teaching method enabled higher cognitive activity levels than the traditional, lecture-based classroom, as assessed using the revised Bloom’s taxonomy.

Trial registration

This study was registered with the University Hospital Medical Information Network Clinical Trials Registry on 08/02/2020 (Unique trial number:UMIN 000039434).