bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiological study on animal bite cases referred to Haji Daii health Center in Kermanshah province, Iran during 2013–2017
Authors: Janatolmakan Maryam , Delpak Mojtaba , Abdi Alireza , Mohamadi Sabah , Andayeshgar Bahare , Khatony Alireza
Published: March 2020

Background

Over thousands of animal bite cases are reported annually worldwide and in Iran placing a large financial burden on the health and economy. The aim of this study was to evaluate the epidemiology of animal bite cases in Kermanshah, Iran through 2013–2017.

Methods

In this cross-sectional study, 5618 animal bite cases in Kermanshah from 2013 to 2017 were studied. Data were analyzed using descriptive and inferential statistics.

Results

In the study period, 5618 animal bite cases were found. The prevalence of animal bites was estimated between 42.55–45.66 per100000 populations during 2013–2017. An increasing significant trend was found for prevalence of animal bites (Average annual percent change [AAPC] + 4.9,P-trend< 0.001) over a 5-years’ time period. The mean age of the subjects was 32.7 ± 18.3 years. Of the studied subjects 76.3% were male, and 34% had non-governmental jobs. Dogs were found as the cause of animal bites in 72% of the cases. Of the studied cases, 82% had received rabies vaccination for three times.

Conclusion

The results showed an increasing significant trend for animal bites in Kermanshah. Development of interventional programs, such as limiting stray dogs, vaccination of dogs and raising public awareness are essential.
Regional differences in the global burden of age-related macular degeneration
Authors: Xu Xiayan , Wu Jing , Yu Xiaoning , Tang Yelei , Tang Xiajing , Shentu Xingchao
Published: March 2020

Background

Age-related Macular Degeneration (AMD) is the leading cause of blindness. This study aims to analyze regional differences on the global burden of AMD and help direct related policy making.

Methods

Disability-adjusted life years (DALY) data were collected from the Global Burden of Disease Study (GBD) 2017 to estimate the AMD burden. Mean education years, human development index (HDI) and Public Health Expenditure were extracted from the Human Development Report 2018, and latitude data were obtained from the Google Earth. These four factors were analyzed to see their importance in regional differences of AMD burden, using Kruskal-Wallis test, Dunn’s multiple comparisons test as well as regression analysis.

Results

Global age-standardized DALY rates have decreased since 2011. Based on the WHO region system, age-standardized DALY rates in African and Eastern Mediterranean region were significantly lower than those of other four regions. Linear regression analysis indicated that age-standardized DALY rates were inversely related to HDI and mean education years.

Conclusions

The age-standardized AMD burden had a decreasing tendency recently. Lower socioeconomic status and fewer education years were associated with higher AMD burden. The finding of this study may highlight the importance of national development and education on relieving AMD burden.
Coexistence of diffuse panbronchiolitis and sarcoidosis revealed during splenectomy: a case report
Authors: Akaba Tomohiro , Takeyama Kiyoshi , Kondo Mitsuko , Kobayashi Fumi , Okabayashi Asako , Sawada Tatsuo , Tagaya Etsuko
Published: March 2020

Background

Sarcoidosis is a systemic granulomatous disease caused by CD4+ cell-dominant inflammation. Meanwhile, diffuse panbronchiolitis is a chronic inflammatory respiratory disease predominantly caused by CD8+ lymphocytes and neutrophils. Herein, we report a rare case of sarcoidosis in which the clinical presentation had become evident as diffuse panbronchiolitis after splenectomy for sarcoidosis.

Case presentation

A 23-year-old Japanese woman was referred to our hospital due to splenomegaly of unknown etiology. Upon admission, chest computed tomography scan revealed centrilobular and randomly distributed small nodules in both lungs. Bronchoalveolar lavage revealed a high proportion of lymphocytes and a decreased CD4/CD8 ratio. However, the biopsy specimens obtained from both the liver and lungs revealed noncaseating epithelioid granulomas, which confirmed the diagnosis of sarcoidosis. The patient underwent splenectomy due to progressive cytopenia and high risk of splenic rupture. After the surgery, the condition of the patient was consistently good for 3 months. Then, she gradually developed productive cough and dyspnea. Both sinus and chest computed tomography scan revealed chronic paranasal sinusitis and deterioration of centrilobular nodules in both lung fields, respectively. The second bronchoalveolar lavage revealed a high proportion of neutrophils, and the bronchoalveolar lavage fluid tested positive for Hemophilus influenzae. The titer of cold agglutinin was elevated, thereby confirming the diagnosis of diffuse panbronchiolitis. On the basis of the clinical and radiological findings, the condition of the patient improved with low-dose macrolide therapy for 3 months.

Conclusions

The coexistence of sarcoidosis and diffuse panbronchiolitis has not been previously reported, and the hidden profiles of diffuse panbronchiolitis may have been revealed by splenectomy.
Finite elements analysis of the temporomandibular joint disc in patients with intra-articular disorders
Authors: Lai Linfeng , Huang Chenyao , Zhou Fan , Xia Fujian , Xiong Guofeng
Published: March 2020

Background

Intra-articular disorders (ID) or anterior and/or medial displacement of the temporomandibular joint disorder (TMJ) disc are the most common form of TMJ dysfunction (TMD). TMD causes changes in the friction coefficient during TMJ movement. Herein, we provided a three-dimensional (3D) finite-elements model (FEM) including the maxilla, disc, and mandible and evaluated the stress distribution with different friction coefficient.

Methods

Fourteen volunteers without TMD and 20 patients with MRI-diagnosed TMD were selected. CT and MRI data were collected to build the 3D FEA model of the mandible and TMJ disc. Stress distribution with different friction coefficient was measured.

Result

In the normal model, stress distribution on the TMJ disc was 2.07 ± 0.17, 1.49 ± 0.14, and 1.41 ± 0.14 MPa with 0.001, 0.3, and 0.4 friction coefficient, respectively. In the TMD model, stress distribution was 3.87 ± 0.15, 7.23 ± 0.22, and 7.77 ± 0.19 MPa respectively.

Conclusion

When the friction coefficient of the side with anterior displacement increased, stress on the disc, condyle and mandible of the opposite side increased. Simultaneously, stress values of the disc, condyle and mandible were higher than those of the normal lateral joint.
Activation of the Nrf2/HO-1 pathway by curcumin inhibits oxidative stress in human nasal fibroblasts exposed to urban particulate matter
Authors: Kim Ji-Sun , Oh Jeong-Min , Choi Hyunsu , Kim Sung Won , Kim Soo Whan , Kim Byung Guk , Cho Jin Hee , Lee Joohyung , Lee Dong Chang
Published: March 2020

Background

Particulate matter (PM) can cause various negative acute and chronic diseases of the respiratory system, including the upper airways. Curcumin has been reported to have anti-inflammatory and anti-oxidative effects; therefore, we investigated the effects of curcumin on nasal fibroblasts exposed to urban PM (UPM).

Methods

Samples of inferior turbinate tissue were obtained from six patients. Flow cytometry was used to assess the levels of reactive oxygen species (ROS) following the treatment of nasal fibroblasts with UPM and/or curcumin. We evaluated the effects of UPM and/or curcumin on the expression of phosphorylated ERK, Nrf2, HO-1, and SOD2 in fibroblasts by Western blotting.

Results

When UPM was applied to nasal fibroblasts, ROS production was significantly increased in a dose-dependent manner. UPM-exposed fibroblasts caused the activation of ERK to increase HO-1 expression and decrease SOD2 expression. Treatment with curcumin reduced the UPM-mediated increase in ROS; this decrease in ROS occurred in a dose-dependent manner. The UPM-induced activation of ERK was inhibited by curcumin. Nrf2 production was also promoted to increase the expression of HO-1 and SOD2 by curcumin.

Conclusion

Curcumin reduced ROS production caused by UPM in human nasal fibroblasts in a dose-dependent manner, suggesting that curcumin has anti-oxidative effects and may be useful in the treatment of nasal diseases caused by UPM, such as allergic and chronic rhinitis.
Neonatal care and community-level treatment seeking for possible severe bacterial infection (PSBI) in Amhara, Ethiopia
Authors: Asfaha Meron D. , Comeau Dawn L. , Spangler Sydney A. , Spratt Brandon L. , Alamineh Lamesgin , Gobezayehu Abebe G. , Cranmer John N.
Published: March 2020

Background

In Ethiopia, neonatal mortality accounts for approximately 54% of under-five deaths with the majority of these deaths driven by infections. Possible Severe Bacterial Infection (PSBI) in neonates is a syndromic diagnosis that non-clinical health care providers use to identify and treat newborns with signs of sepsis. In low- and middle–income countries, referral to a hospital may not be feasible due to transportation, distance or finances. Growing evidence suggests health extension workers (HEWs) can identify and manage PSBI at the community level when referral to a hospital is not possible. However, community-based PSBI care strategies have not been widely scaled-up. This study aims to understand general determinants of household-level care as well as household care seeking and decision-making strategies for neonatal PSBI symptoms.

Methods

We conducted eleven focus group discussions (FGDs) to explore illness recognition and care seeking intentions from four rural kebeles in Amhara, Ethiopia. FGDs were conducted among mothers, fathers and households with recruitment stratified among households that have had a newborn with at least one symptom of PSBI (Symptomatic Group), and households that have had a newborn regardless of the child’s health status (Community Group). Data were thematically analyzed using MAXQDA software.

Results

Mothers were described as primary caretakers of the newborn and were often appreciated for making decisions for treatment, even when the father was not present. Type of care accessed was often dependent on conceptualization of the illness as simple or complex. When symptoms were not relieved with clinical care, or treatments at facilities were perceived as ineffective, alternative methods were sought. Most participants identified the health center as a reliable facility. While designed to be the first point of access for primary care, health posts were not mentioned as locations where families seek clinical treatment.

Conclusions

This study describes socio-contextual drivers for PSBI treatment at the community level. Future programming should consider the role community members have in planning interventions to increase demand for neonatal care at primary facilities. Encouragement of health post utilization could further allow for heightened accessibility-acceptability of a simplified PSBI regimen.
Pragmatic adaptation of implementation research measures for a novel context and multiple professional roles: a factor analysis study
Authors: Smith Justin D. , Rafferty Miriam R. , Heinemann Allen W. , Meachum Mariah K. , Villamar Juan , Lieber Richard L. , Brown C. Hendricks
Published: March 2020

Background

Although some advances have been made in recent years, the lack of measures remains a major challenge in the field of implementation research. This results in frequent adaptation of implementation measures for different contexts—including different types of respondents or professional roles—than those for which they were originally developed and validated. The psychometric properties of these adapted measures are often not rigorously evaluated or reported. In this study, we examined the internal consistency, factor structure, and structural invariance of four well-validated measures of inner setting factors across four groups of respondents. The items in these measures were adapted as part of an evaluation of a large-scale organizational change in a rehabilitation hospital, which involved transitioning to a new building and a new model of patient care, facilitated by a significant redesign of patient care and research spaces.

Methods

Items were tailored for the context and perspective of different respondent groups and shortened for pragmatism. Confirmatory factor analysis was then used to test study hypotheses related to fit, internal consistency, and invariance across groups.

Results

The survey was administered to approximately 1208 employees; 785 responded (65% response rate) across the roles of clinician, researcher, leader, support staff, or dual clinician and researcher. For each of the four scales, confirmatory factor analysis demonstrated adequate fit that largely replicated the original measure. However, a few items loaded poorly and were removed from the final models. Internal consistencies of the final scales were acceptable. For scales that were administered to multiple professional roles, factor structures were not statistically different across groups, indicating structural invariance.

Conclusions

The four inner setting measures were robust for use in this new context and across the multiple stakeholder groups surveyed. Shortening these measures did not significantly impair their measurement properties; however, as this study was cross sectional, future studies are required to evaluate the predictive validity and test-retest reliability of these measures. The successful use of adapted measures across contexts, across and between respondent groups, and with fewer items is encouraging, given the current emphasis on designing pragmatic implementation measures.
Perspectives on program mis-implementation among U.S. local public health departments
Authors: Allen Peg , Jacob Rebekah R. , Parks Renee G. , Mazzucca Stephanie , Hu Hengrui , Robinson Mackenzie , Dobbins Maureen , Dekker Debra , Padek Margaret , Brownson Ross C.
Published: March 2020

Background

Public health resources are limited and best used for effective programs. This study explores associations of mis-implementation in public health (ending effective programs or continuing ineffective programs) with organizational supports for evidence-based decision making among U.S. local health departments.

Methods

The national U.S. sample for this cross-sectional study was stratified by local health department jurisdiction population size. One person was invited from each randomly selected local health department: the leader in chronic disease, or the director. Of 600 selected, 579 had valid email addresses; 376 completed the survey (64.9% response). Survey items assessed frequency of and reasons for mis-implementation. Participants indicated agreement with statements on organizational supports for evidence-based decision making (7-point Likert).

Results

Thirty percent (30.0%) reported programs often or always ended that should have continued (inappropriate termination); organizational supports for evidence-based decision making were not associated with the frequency of programs ending. The main reason given for inappropriate termination was grant funding ended (86.0%). Fewer (16.4%) reported programs often or always continued that should have ended (inappropriate continuation). Higher perceived organizational supports for evidence-based decision making were associated with less frequent inappropriate continuation (odds ratio = 0.86, 95% confidence interval 0.79, 0.94). All organizational support factors were negatively associated with inappropriate continuation. Top reasons were sustained funding (55.6%) and support from policymakers (34.0%).

Conclusions

Organizational supports for evidence-based decision making may help local health departments avoid continuing programs that should end. Creative mechanisms of support are needed to avoid inappropriate termination. Understanding what influences mis-implementation can help identify supports for de-implementation of ineffective programs so resources can go towards evidence-based programs.
Assessing medical impoverishment and associated factors in health care in Ethiopia
Authors: Obse Amarech G. , Ataguba John E.
Published: March 2020

Background

About 5% of the global population, predominantly in low- and middle-income countries, is forced into poverty because of out-of-pocket (OOP) health spending. In most countries in sub-Saharan Africa, the share of OOP health spending in current health expenditure exceeds 35%, increasing the likelihood of impoverishment. In Ethiopia, OOP payments remained high at 37% of current health expenditure in 2016. This study assesses the impoverishment resulting from OOP health spending in Ethiopia and the associated factors.

Methods

This paper uses data from the Ethiopian Household Consumption Expenditure Survey (HCES) 2010/11. The HCES covered 10,368 rural and 17,664 urban households. OOP health spending includes spending on various outpatient and inpatient services. Impoverishing impact of OOP health spending was estimated by comparing poverty estimates before and after OOP health spending. A probit model was used to assess factors that are associated with impoverishment.

Results

Using the Ethiopian national poverty line of Birr 3781 per person per year (equivalent to US$2.10 per day), OOP health spending pushed about 1.19% of the population (i.e. over 957,169 individuals) into poverty. At the regional level, impoverishment ranged between 2.35% in Harari and 0.35% in Addis Ababa. Living in rural areas (highland, moderate, or lowland) increased the likelihood of impoverishment compared to residing in an urban area. Households headed by males and adults with formal education are less likely to be impoverished by OOP health spending, compared to their counterparts.

Conclusion

In Ethiopia, OOP health spending impoverishes a significant number of the population. Although the country had piloted and initiated many reforms, e.g. the fee waiver system and community-based health insurance, a significant proportion of the population still lacks financial protection. The estimates of impoverishment from out-of-pocket payments reported in this paper do not consider individuals that are already poor before paying out-of-pocket for health services. It is important to note that this population may either face deepening poverty or forgo healthcare services if a need arises. More is therefore required to provide financial protection to achieve universal health coverage in Ethiopia, where the informal sector is relatively large.
Persistent DNA damage triggers activation of the integrated stress response to promote cell survival under nutrient restriction
Authors: Clementi Elena , Inglin Larissa , Beebe Erin , Gsell Corina , Garajova Zuzana , Markkanen Enni
Published: March 2020

Background

Base-excision repair (BER) is a central DNA repair mechanism responsible for the maintenance of genome integrity. Accordingly, BER defects have been implicated in cancer, presumably by precipitating cellular transformation through an increase in the occurrence of mutations. Hence, tight adaptation of BER capacity is essential for DNA stability. However, counterintuitive to this, prolonged exposure of cells to pro-inflammatory molecules or DNA-damaging agents causes a BER deficiency by downregulating the central scaffold protein XRCC1. The rationale for this XRCC1 downregulation in response to persistent DNA damage remains enigmatic. Based on our previous findings that XRCC1 downregulation causes wide-ranging anabolic changes, we hypothesised that BER depletion could enhance cellular survival under stress, such as nutrient restriction.

Results

Here, we demonstrate that persistent single-strand breaks (SSBs) caused by XRCC1 downregulation trigger the integrated stress response (ISR) to promote cellular survival under nutrient-restricted conditions. ISR activation depends on DNA damage signalling via ATM, which triggers PERK-mediated eIF2α phosphorylation, increasing translation of the stress-response factor ATF4. Furthermore, we demonstrate that SSBs, induced either through depletion of the transcription factor Sp1, responsible for XRCC1 levels, or through prolonged oxidative stress, trigger ISR-mediated cell survival under nutrient restriction as well. Finally, the ISR pathway can also be initiated by persistent DNA double-strand breaks.

Conclusions

Our results uncover a previously unappreciated connection between persistent DNA damage, caused by a decrease in BER capacity or direct induction of DNA damage, and the ISR pathway that supports cell survival in response to genotoxic stress with implications for tumour biology and beyond.
In vitro screening antiviral activity of Thai medicinal plants against porcine reproductive and respiratory syndrome virus
Authors: Arjin Chaiwat , Pringproa Kidsadagon , Hongsibsong Surat , Ruksiriwanich Warintorn , Seel-audom Mintra , Mekchay Supamit , Sringarm Korawan
Published: March 2020

Background

Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) results in economic losses in the swine industry globally. Several studies have investigated the use of plant extracts in the prevention and control of PRRS outbreaks. Thai medicinal plants may be useful for treating PRRSV infection in pigs. Therefore, we investigated the in vitro anti-PRRSV and antioxidant properties of seven Thai medicinal plants:Caesalpinia sappanLinn.,Garcinia mangostanaLinn.,Houttuynia cordata,Perilla frutescens,Clinacanthus nutans,Phyllanthus emblica, andTiliacora triandra.

Results

Using antiviral screening, we observed thatT. triandraextract strongly inhibited PRRSV infectivity in MARC-145 cells [virus titer 3.5 median tissue culture infective dose (TCID50)/ml (log10)] at 24 h post-infection, whereasC. sappanextract strongly inhibited PRRSV replication [virus titer 2.5 TCID50/ml (log10)] at 72 h post-infection.C. sappanextract had the highest total phenolic content [220.52 mM gallic acid equivalent/g] and lowest half-maximal inhibitory concentration [1.17 mg/ml in 2,2-diphenyl-1-picrylhydrazyl and 2.58 mg/ml in 2,2-azino-bis (3-ethylbenzothiazo-line-6-sulfonic acid) diammonium salt].

Conclusion

T. triandraextract could inhibit PRRSV infectivity, whereasC. sappanextract was the most effective in inhibiting PRRSV replication in MARC-145 cells. This study elucidates the antiviral activities of Thai medicinal plant extracts in vivo. The results promise that Thai medicinal plant extracts, particularlyT. triandraandC. sappanextracts, can be developed into pharmaceutical drugs for the prevention of PRRS in pigs.
Identification of miRNA-mRNA associations in hepatocellular carcinoma using hierarchical integrative model
Authors: Varghese Rency S. , Zhou Yuan , Barefoot Megan , Chen Yifan , Di Poto Cristina , Balla Abdalla Kara , Oliver Everett , Sherif Zaki A. , Kumar Deepak , Kroemer Alexander H. , Tadesse Mahlet G. , Ressom Habtom W.
Published: March 2020

Background

The established role miRNA-mRNA regulation of gene expression has in oncogenesis highlights the importance of integrating miRNA with downstream mRNA targets. These findings call for investigations aimed at identifying disease-associated miRNA-mRNA pairs. Hierarchical integrative models (HIM) offer the opportunity to uncover the relationships between disease and the levels of different molecules measured in multiple omic studies.

Methods

The HIM model we formulated for analysis of mRNA-seq and miRNA-seq data can be specified with two levels: (1) a mechanistic submodel relating mRNAs to miRNAs, and (2) a clinical submodel relating disease status to mRNA and miRNA, while accounting for the mechanistic relationships in the first level.

Results

mRNA-seq and miRNA-seq data were acquired by analysis of tumor and normal liver tissues from 30 patients with hepatocellular carcinoma (HCC). We analyzed the data using HIM and identified 157 significant miRNA-mRNA pairs in HCC. The majority of these molecules have already been independently identified as being either diagnostic, prognostic, or therapeutic biomarker candidates for HCC. These pairs appear to be involved in processes contributing to the pathogenesis of HCC involving inflammation, regulation of cell cycle, apoptosis, and metabolism. For further evaluation of our method, we analyzed miRNA-seq and mRNA-seq data from TCGA network. While some of the miRNA-mRNA pairs we identified by analyzing both our and TCGA data are previously reported in the literature and overlap in regulation and function, new pairs have been identified that may contribute to the discovery of novel targets.

Conclusion

The results strongly support the hypothesis that miRNAs are important regulators of mRNAs in HCC. Furthermore, these results emphasize the biological relevance of studying miRNA-mRNA pairs.
Circular RNA circVAPA knockdown suppresses colorectal cancer cell growth process by regulating miR-125a/CREB5 axis
Authors: Zhang Xiaoyu , Xu Yingying , Yamaguchi Kenji , Hu Jinping , Zhang Lianbo , Wang Jianfeng , Tian Jifeng , Chen Wanying
Published: March 2020

Background

Colorectal cancer (CRC) is a malignant tumor, and the overall prognosis of patients with advanced CRC is still unsatisfactory. Circular RNAs (circRNAs) vesicle-associated membrane protein-associated protein A (circVAPA) could act as an underlying biomarker in CRC. This study aimed to explore the mechanism of circVAPA in the regulation of CRC growth.

Methods

CircVAPA level was measured in CRC tumor tissues. The expression levels of circVAPA, VAPA mRNA, microRNA-125a (miR-125a), and cAMP response element binding 5 (CREB5) in CRC cells were detected by RT-qPCR. Cell cycle progression, migration and invasion, extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were measured by flow cytometry, transwell assays and Seahorse XF96 Glycolysis Analyzer, severally. The levels of glucose uptake, lactate and ATP production were examined by Glucose Uptake Colorimetric Assay kit, Lactate Assay kit and ATP Colorimetric Assay kit, respectively. The interaction between miR-125a and circVAPA or CREB5 was predicted by Starbase or DIANA TOOL, and verified by the dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays.

Results

CircVAPA level was up-regulated in CRC tumor tissues. Expression levels of circVAPA and CREB5 were increased, and miR-125a was decreased in CRC cells. CircVAPA knockdown repressed CRC cells cycle progression, migration, invasion and glycolysis. CircVAPA acted as a miR-125a sponge to regulate CREB5 expression. Rescue assay confirmed that miR-125a deletion or CREB5 overexpression weakened the inhibitory effect of circVAPA knockdown on CRC growth.

Conclusion

Our studies disclosed that circVAPA knockdown suppressed CRC cells cycle progression, migration, invasion and glycolysis partly by modulating miR-125a/CREB5 axis, suggesting a potential therapeutic strategy for CRC treatment.
Effects of body condition on the insulin resistance, lipid metabolism and oxidative stress of lactating dairy cows
Authors: Wu Jiajin , Liu Jianxin , Wang Diming
Published: March 2020

Background

Overconditioned dairy cows are prone to greater insulin resistance in transition to successfully adapt to negative energy balance. The associations among body condition score (BCS), insulin resistance, lipid metabolism and oxidative stress in cows during late lactation with positive energy balance remain to be elucidated.

Methods

The objectives of this study were to investigate insulin sensitivity and oxidative status in late lactating dairy cows with different BCS but similar milk production, parity and days in milk. Forty-two multiparous Holstein cows were fed the same diet under the same management and divided into three groups based on BCS: low BCS (LBCS; BCS ≤ 2.75; n = 12), medium BCS (MBCS; 3.0 ≤ BCS ≤ 3.5; n = 15) or high BCS (HBCS; BCS ≥ 3.75; n = 15). Blood samples used for analysis of biochemical and hematological parameters were collected from the coccygeal vein at the end of experiment.

Results

The concentrations of insulin and nonesterified fatty acid were higher and the revised quantitative insulin sensitivity check index (RQUICKI) was lower in HBCS cows than in LBCS and MBCS cows. These results suggest that insulin resistance exacerbates lipolysis in HBCS cows. Serum concentrations of very low-density lipoprotein, apolipoprotein A-I, and apolipoprotein B were lower in HBCS cows than in LBCS or MBCS cows. Although LBCS and MBCS cows had higher reactive oxygen species levels than did HBCS cows, the malondialdehyde concentration was not different among cows with different BCS. Ceruloplasmin activity was higher in MBCS and HBCS cows than in LBCS cows, but superoxide dismutase, glutathione peroxidase, and paraoxonase activities were not different among cows with different BCS. Despite the higher percentage of granulocytes in MBCS cows than in HBCS cows, no differences were found in leukocyte counts, red blood cell profiles and platelet profiles among the cows in the three groups.

Conclusions

Results of this study showed that compared with MBCS and LBCS cows, HBCS cows at late lactation stage may have accumulated more hepatic triacylglycerol and lower antioxidant potential due to greater insulin resistance.
Drug affinity and targeted delivery: double functionalization of silk spheres for controlled doxorubicin delivery into Her2-positive cancer cells
Authors: Kucharczyk Kamil , Florczak Anna , Deptuch Tomasz , Penderecka Karolina , Jastrzebska Katarzyna , Mackiewicz Andrzej , Dams-Kozlowska Hanna
Published: March 2020

Background

The optimal drug delivery system should be biocompatible, biodegradable, and allow the sustained release of the drug only after it reaches the target cells. Silk, as a natural polymer, is a great candidate for building drug carriers. Genetically engineered silks offer the possibility of functionalization. Previously, we characterized bioengineered silk spheres that were functionalized with H2.1 peptide that selectively delivered a drug to Her2-positive cancer cells. However, drug leakage from the silk spheres showed the need for improved control.

Results

To control the drug loading and release, we designed and produced functional silk (DOXMS2) that contains a DOX peptide with an affinity for doxorubicin. The DOXMS2 spheres showed the decreased release of doxorubicin compared with MS2 particles. Next, the DOXMS2 silk was blended with the H2.1MS1 polymer to improve the control of doxorubicin binding and release into Her2-positive cancer cells. The H2.1MS1:DOXMS2 particles showed the highest doxorubicin-loading capacity and binding per cell, which resulted in the highest cytotoxic effect compared with that of other sphere variants. Since drug release at a pH of 7.4 from the blended H2.1MS1:DOXMS2 particles was significantly lower than from blended spheres without DOXMS2 silk, this indicated that such particles could control the release of the drug into the circulatory system before the carrier reached the tumor site.

Conclusions

This strategy, which is based on the blending of silks, allows for the generation of particles that deliver drugs in a controlled manner.
Patterns of tobacco and e-cigarette use status in India: a cross-sectional survey of 3000 vapers in eight Indian cities
Authors: Sharan Rajeshwar Nath , Chanu Tongbram Malemnganbi , Chakrabarty Tapan Kumar , Farsalinos Konstantinos
Published: March 2020

Background

Tobacco smoking is one of the biggest and avoidable public health threats in the world, especially in low- and middle-income countries. India represents a highly complex public health environment due to the large number of smokers and complexities arising from tobacco use in different forms, including a variety of smokeless tobacco (SLT) products. Electronic cigarettes, an alternative nicotine delivery system with significantly less harmful emissions than smoke, could be an option for those who are unable to achieve smoking abstinence using other available means. This study, which we believe is the first of this kind in India, was conducted to obtain data on the characteristics and tobacco use profile of e-cigarette users (vapers) in India.

Methods

An interview-based survey was performed in the 8 largest metropolitan cities in India using a convenience sampling approach involving a total of 3000 subjects. Inclusion criteria were being a current e-cigarette user and aged 18 years or more. Interviewers were asked to continue recruitment until a total sample of 375 was reached in each target city.

Results

A total of 3000 vapers (81.4% males and 18.6% females, median age 29 years) participated to the study. The majority (80%) were first exposed to nicotine via tobacco smoking, SLT use, or both. Most of the subjects (79%) believed that e-cigarettes were less harmful than smoking. The vast majority of smokers (71.3%) reported smoking cessation (30.0%) or reduction in consumption (41.3%) with the help of e-cigarettes. Similar changes were observed in SLT users. Participants reported minimal side effects and some health benefits after e-cigarette use initiation.

Conclusion

Indian vapers who participated to this study were predominantly smokers and SLT users before e-cigarette use initiation, with the majority subsequently quitting or reducing tobacco use. Minimal side effects of e-cigarette were experienced, while some health benefits were also reported.
“Am I gonna get in trouble for acknowledging my will to be safe?”: Identifying the experiences of young sexual minority men and substance use in the context of an opioid overdose crisis
Authors: Goodyear Trevor , Mniszak Caroline , Jenkins Emily , Fast Danya , Knight Rod
Published: March 2020

Background

North America and other parts of the globe are in the midst of a public health emergency related to opioid overdoses and a highly contaminated illicit drug supply. Unfortunately, there is a substantial gap in our understandings about how this crisis affects key populations not conventionally identified within overdose-related surveillance data. This gap is particularly pronounced for gay, bisexual, and other men who have sex with men (sexual minority men)—a population that experiences substance use-related inequities across adolescence and young adulthood.

Methods

We draw on in-depth semi-structured interviews conducted in 2018 with a diverse sample (N = 50) of sexual minority men ages 15–30 who use substances and live in Vancouver, Canada, to identify how patterns and contexts of substance use are occurring in the context of the opioid overdose crisis.

Results

Our analysis revealed three themes: awareness, perceptions, and experiences of risk; strategies to mitigate risk; and barriers to safer substance use. First, participants described how they are deeply impacted by the contaminated illicit drug supply, and how there is growing apprehension that fatal and non-fatal overdose risk is high and rising. Second, participants described how procuring substances from “trustworthy” drug suppliers and other harm reduction strategies (e.g., drug checking technologies, Naloxone kits, not using alone) could reduce overdose risk. Third, participants described how interpersonal, service-related, and socio-structural barriers (e.g., drug criminalization and the lack of a regulated drug supply) limit opportunities for safer substance use.

Conclusions

Equity-oriented policies and programming that can facilitate opportunities for safer substance use among young sexual minority men are critically needed, including community- and peer-led initiatives, access to low-barrier harm reduction services within commonly frequented social spaces (e.g., Pride, night clubs, bathhouses), nonjudgmental and inclusive substance use-related health services, the decriminalization of drug use, and the provision of a safe drug supply.
Unusually persistent Gαi-signaling of the neuropeptide Y2 receptor depletes cellular Gi/o pools and leads to a Gi-refractory state
Authors: Ziffert Isabelle , Kaiser Anette , Babilon Stefanie , Mörl Karin , Beck-Sickinger Annette G.
Published: March 2020

Background

A sensitive balance between receptor activation and desensitization is crucial for cellular homeostasis. Like many other GPCR, the human neuropeptide Y2 receptor (hY2R) undergoes ligand dependent activation and internalization into intracellular compartments, followed by recycling to the plasma membrane. This receptor is involved in the pathophysiology of distinct diseases e.g. epilepsy and cancer progression and conveys anorexigenic signals which makes it an interesting and promising anti-obesity target. However, Y2R desensitization was observed after daily treatment with a selective PYY13–36 analog in vivo by a yet unknown mechanism.

Materials

We studied the desensitization and activatability of recycled Y2R in transiently transfected HEK293 cells as well as in endogenously Y2R expressing SH-SY5Y and SMS-KAN cells. Results were evaluated by one-way ANOVA and Tukey post test.

Results

We observed strong desensitization of the Y2R in a second round of stimulation despite its reappearance at the membrane. Already the first activation of the Y2R leads to depletion of the functional cellular Gαi/o protein pool and consequently desensitizes the linked signal transduction pathways, independent of receptor internalization. This desensitization also extends to other Gαi/o-coupled GPCR and can be detected in transfected HEK293 as well as in SH-SY5Y and SMS-KAN cell lines, both expressing the Y2R endogenously. By overexpression of chimeric Gαqi proteins in a model system, activation has been rescued, which identifies a critical role of the G protein status for cellular signaling. Furthermore, Y2R displays strong allosteric coupling to inhibitory G proteins in radioligand binding assays, and loses 10-fold affinity in the G protein-depleted state observed after activation, which can be largely abrogated by overexpression of the Gαi-subunit.

Conclusion

The unusually persistent Gαi-signaling of the Y2R leads to a state of cellular desensitization of the inhibitory Gαi-pathway. The strong allosteric effects of the Y2R-Gαi-interaction might be a mechanism that contributes to the burst of Gαi-signaling, but also serves as a mechanism to limit the Y2-mediated signaling after recycling. Thus, the cell is left in a refractory state, preventing further Gαi-signaling of the Y2R itself but also other Gαi/o-coupled receptors by simply controlling the repertoire of downstream effectors.

Graphical abstract
IL-9 and IL-9-producing cells in tumor immunity
Authors: Wan Jie , Wu Yinqiu , Ji Xiaoyun , Huang Lan , Cai Wei , Su Zhaoliang , Wang Shengjun , Xu Huaxi
Published: March 2020

Interleukin (IL)-9 belongs to the IL-2Rγc chain family and is a multifunctional cytokine that can regulate the function of many kinds of cells. It was originally identified as a growth factor of T cells and mast cells. In previous studies, IL-9 was mainly involved in the development of allergic diseases, autoimmune diseases and parasite infections. Recently, IL-9, as a double-edged sword in the development of cancers, has attracted extensive attention. Since T-helper 9 (Th9) cell-derived IL-9 was verified to play a powerful antitumor role in solid tumors, an increasing number of researchers have started to pay attention to the role of IL-9-skewed CD8+ T (Tc9) cells, mast cells and Vδ2 T cell-derived IL-9 in tumor immunity. Here, we review recent studies on IL-9 and several kinds of IL-9-producing cells in tumor immunity to provide useful insight into tumorigenesis and treatment.

Graphical abstract
Inpatient mortality in transition-aged youth with rheumatic disease: an analysis of the National Inpatient Sample
Authors: Jensen Paul T. , Koh Keumseok , Cash Rebecca E. , Ardoin Stacy P. , Hyder Ayaz
Published: March 2020

Background

Transition from pediatric to adult care is a vulnerable time for youth with chronic diseases. In youth with rheumatic disease, studies show high rates of loss to follow up and increased disease activity. However, mortality data are lacking. In this study, we assessed whether transitional age is a risk factor for inpatient mortality.

Methods

We analyzed the 2012–2014 National Inpatient Sample database, a representative sample of discharges in the United States. Individuals with rheumatic diseases were identified by International Statistical Classification of Disease – 9 (ICD-9) codes at time of discharge. Youth were categorized into three age groups: pre-transitional (11–17), transitional (18–24) and post transitional (25–31). We fitted univariable and multivariable logistic regression models to assess whether transitional age was a risk factor for inpatient mortality.

Results

There were 30,269 hospital discharges which met our inclusion criteria of diagnosis and age. There were 195 inpatient deaths (0.7%). The most common causes of death were infection (39.5%), pulmonary disease (13.8%), and cardiac disease (11.2%). The Odds ratio for inpatient mortality of a transitional-aged individual was 1.18 compared to controls (p = 0.3). Black race (OR = 1.4), male sex (OR = 1.75), and a diagnosis of systemic sclerosis (OR = 4.81) or vasculitis (OR = 2.85) were the greatest risk factors of inpatient mortality.

Conclusion

Transitional age was not a risk factor for inpatient mortality in this study. We did identify other risk factors other than age. Further studies are required to assess if there is an increased risk of mortality in outpatients of the transitional age group.
DDX5 potentiates HIV-1 transcription as a co-factor of Tat
Authors: Sithole Nyaradzai , Williams Claire A. , Abbink Truus E. M. , Lever Andrew M. L.
Published: March 2020

Background

HIV-1 does not encode a helicase and hijacks those of the cell for efficient replication. We and others previously showed that the DEAD box helicase, DDX5, is an essential HIV dependency factor. DDX5 was recently shown to be associated with the 7SK snRNP. Cellular positive transcription elongation factor b (P-TEFb) is bound in an inactive form with HEXIM1/2 on 7SK snRNP. The Tat/P-TEFb complex is essential for efficient processivity of Pol II in HIV-1 transcription elongation and Tat competes with HEXIM1/2 for P-TEFb. We investigated the precise role of DDX5 in HIV replication using siRNA mediated knockdown and rescue with DDX5 mutants which prevent protein–protein interactions and RNA and ATP binding.

Results

We demonstrate a critical role for DDX5 in the Tat/HEXIM1 interaction. DDX5 acts to potentiate Tat activity and can bind both Tat and HEXIM1 suggesting it may facilitate the dissociation of HEXIM1/2 from the 7SK-snRNP complex, enhancing Tat/P-TEFb availability. We show knockdown of DDX5 in a T cell line significantly reduces HIV-1 infectivity and viral protein production. This activity is unique to DDX5 and cannot be substituted by its close paralog DDX17. Overexpression of DDX5 stimulates the Tat/LTR promoter but suppresses other cellular and viral promoters. Individual mutations of conserved ATP binding, RNA binding, helicase related or protein binding motifs within DDX5 show that the N terminal RNA binding motifs, the Walker B and the glycine doublet motifs are essential for this function. The Walker A and RNA binding motifs situated on the transactivation domain are however dispensable.

Conclusion

DDX5 is an essential cellular factor for efficient HIV transcription elongation. It interacts with Tat and may potentiate the availability of P-TEFb through sequestering HEXIM1.
Diasporic medical tourism: a scoping review of quantitative and qualitative evidence
Authors: Mathijsen Aneta , Mathijsen François Pierre
Published: March 2020

Background

There is a growing recognition of the significance of the diasporic dimension of medical travel. Explanations of medical tourism are increasingly presented in a wider context of transnationalism, diaspora and migration. Yet diaspora and cross-border travellers rarely get through the broader narrative of medical travel.

Objective

Our aim in this scoping review was to extend the current knowledge on the emerging subject of diasporic travels for medical purposes. Specifically, we reviewed the existing literature on what is known about the determinants and motivational factors of diasporic medical tourism; its geographic scope and its quantitative estimation.

Methods

Using a scoping review methodology, we conducted the search in seven electronic databases. It resulted in 210 records retrieved. Ultimately, 28 research papers and 6 non-research papers (published between 2002 and 2019) met the following criteria: 1) focus on healthcare and health-related practices, 2) transnational perspective, 3) healthcare consumption in the country of origin (homeland) while being a resident of another country, 4) published in English.

Results

The findings from our review highlighted the importance of diasporic medical patients who had been researched and analysed on four continents. Even though quantitative evidence has been scarce, the data analysed in the scoping review pointed to the existence of non-negligible level of diasporic medical tourism in Northern America, and in Europe. Various motivational factors were enumerated with their frequency of occurrence: medical culture (12), time availability (“by the way of being home”) (9), communication (6), dissatisfaction with the current system (6), healthcare insurance status (5), quality of healthcare (5), second opinion (3), and value for money (3).

Conclusion

Diasporic medical tourists constitute an attractive segment of consumers that is still not well understood and targeted. They are part of transnational communities that cultivate the links between the two nations. They simultaneously participate in bi-lateral healthcare systems via return visits which impact the health systems of sending and receiving countries in a substantial way. In the current globalised, connected and migratory context, transnationalism seems to represent an answer to many local healthcare-related barriers. Sending and receiving countries have put in place an array of programmes and policies addressed to the diasporic medical travellers.
Exploring the challenges and opportunities towards optimal breastfeeding in Ethiopia: a formative qualitative study
Authors: Gebremariam Kidane Tadesse , Zelenko Oksana , Hadush Znabu , Mulugeta Afework , Gallegos Danielle
Published: March 2020

Background

Breastfeeding, particularly exclusive breastfeeding, is essential to ensure the short- and long-term health of infants and mothers. Sub-optimal breastfeeding practices currently take place in low income countries contributing to morbidity and mortality. This research explored the challenges and opportunities around exclusive breastfeeding in a large city in Ethiopia to inform a larger breastfeeding intervention.

Methods

Fathers and mothers who had children less than 2 years of age, and who could speak, and understand Tigrigna were recruited from two health centres located in Mekelle, Ethiopia. Two focus group discussions (FGDs) with fathers and two FGDs with mothers (n = 42) were conducted using a semi-structured interview guide to explore the challenges and opportunities related to breastfeeding. Discussions were audio-recorded and transcribed in Tigrigna and translated to English. The data were manually analysed using thematic analysis, generating open codes which were grouped to form themes.

Results

Four themes with 11 sub-themes emerged. The themes identifies were: conflicted emotions on the birth of baby (feeling happy and feeling worried); perspectives on intergenerational approaches (old-fashioned beliefs of grandparents and the power of science, breastfeeding in public, breastfeeding knowledge); gender roles as barriers and enablers (the burden on women, changes in men’s roles and the financial status of the household); the role of healthcare (delivery of health information to parents, the role of health care providers and perceptions of inadequate milk supply).

Conclusion

Parents reported a range of opportunities with respect to breastfeeding, including the power of a scientific approach, the positive role of healthcare, and shifts within gender roles that maximized the potential support from fathers. However, there remains a tension between the beliefs of older generations and current best-practice. Parents continue to need ongoing support in order to practice optimal breastfeeding.