bluuebunny/crossref_metadata_2025 huggingface dataset:
Musculoskeletal symptoms and their associated risk factors among Saudi office workers: a cross-sectional study
Authors: AlOmar Reem S. , AlShamlan Nouf A. , Alawashiz Saad , Badawood Yaser , Ghwoidi Badr A. , Abugad Hassan
Published: September 2021

Background

Musculoskeletal disorders are common worldwide. Several factors are suggested in their aetiology, one of which is ergonomics alongside other individual factors. This study aims at investigating the prevalence of musculoskeletal disorders among administrative office workers at a large university in Saudi Arabia.

Methods

This cross-sectional study recruited office workers at a Saudi university. A questionnaire was used that involved three sections, the first section consisted of sociodemographic questions, the second included the Rapid Office Strain Assessment (ROSA) checklist to assess ergonomic factors possibly involved, and the third included the Nordic Musculoskeletal Questionnaire to measure the outcome. Bi-variate analyses were performed by Chi-Squared tests and T-tests where appropriate, and a multivariable logistic regression was done to yield odds ratios (OR) and 95% confidence intervals (CIs).

Results

The prevalence of musculoskeletal symptoms in any region during the past 12 months preceding the study was 84.5%, and only 30% have sought medical advice. The most common area of complaint was the lower back (54.5%). After adjustment, age and years of experience were positively associated with musculoskeletal symptoms (OR = 1.04, 95% CI = 1.01–1.09 and OR = 1.10, 95% CI = 1.05–1.15). Normal weight was associated with a significant reduction in risk (OR = 0.10, 95% CI = 0.05–0.18). ROSA score was an independent risk factor (OR = 1.77, 95% CI = 1.05–2.96).

Conclusions

Musculoskeletal symptoms were highly prevalent in the current sample. Identified predictors may support the need for interventions to reduce risk.
The application of enhanced recovery after surgery and negative-pressure wound therapy in the perioperative period of elderly patients with colorectal cancer
Authors: Liu Han-rong , Yang Ping , Han Song , Zhang Yu , Zhu Hui-yin
Published: September 2021

Objective

To Explore the perioperative application of enhanced recovery after surgery (ERAS) and negative-pressure wound therapy in the elderly patients with colorectal cancer.

Methods

A retrospective clinical data were studied in the patients with colorectal cancer in Department of General Surgery in Shanghai Fourth People,s Hospital (from March, 2017 to March, 2019), One hundred and fifty patients with undergoing radical surgery for colorectal cancer were divided into two groups: ERAS group (n = 76 cases, accepting ERAS management) and Conventional treatment(CT) group (n = 74 cases, accepting traditional treatment), Bleeding in operation, the time of postoperative anal flatus, number of wound dressing changing, time of wound healing, the length of postoperative hospital stay, readmission rate, postoperative complication, were compared between the two groups.

Results

ERAS was associated with less bleeding in operation, less Wound fat liquefaction, less wound dressing changing, less time of wound healing, less time of postoperative anal flatus compare to CT group (P < 0.05); anastomotic fistula, readmission rate is similar in two groups (P > 0.05).

Conclusion

The modified ERAS can be safely applied to the perioperative period of elderly colorectal cancer patients and promote recovery; negative-pressure wound therapy is helpful for wound healing and promoting rehabilitation.
Obesity management in polycystic ovary syndrome: disparity in knowledge between obstetrician-gynecologists and reproductive endocrinologists in China
Authors: Ma Ruilin , Zou Ying , Wang Wei , Zheng Qingmei , Feng Ying , Dong Han , Tan Zhangyun , Zeng Xiaoqin , Zhao Yinqing , Deng Yan , Wang Yanfang , Sun Aijun
Published: September 2021

Background

Obesity is associated with the development of polycystic ovary syndrome (PCOS) and contributes substantially to metabolic abnormalities in women with PCOS. The study aimed to describe and compare the practices of physicians in the diagnosis, evaluation, and treatment of obesity in patients with PCOS.

Methods

Reproductive endocrinologists (Repro-Endo) and obstetrician-gynecologists (non-reproductive medicine specialty, OB-Gyn) in China participated in a survey, and their responses were analyzed using χ2 tests, Fisher exact tests, and multivariable logistic regression analysis.

Results

The study analyzed 1318 survey responses (85.8% OB-Gyn; 97.3% women). Body mass index was the most common diagnostic criterion for obesity; only 1.3% of participants measured waist circumference to identify abdominal obesity. More Repro-Endo participants (25% of all participants) enquired about the psychological problems of patients with obesity than OB-Gyn participants, and 42.5% of participants reported ordering both a lipid profile and oral glucose tolerance test (OGTT) for patients with obesity and PCOS. Multivariable analysis, that included physician’s specialty, age, hospital grade, and number of patients with PCOS seen annually, revealed that OB-Gyn participants were less likely to order OGTT (OR, 0.3; 95% CI, 0.2–0.4) and lipid profile (OR, 0.2; 95% CI, 0.1–0.3) than Repro-Endo participants. The most common treatments for patients with PCOS were lifestyle modification (> 95%) and metformin (> 80%). More Repro-Endo participants prescribed metformin at a dose of 1.5 g/day compared with OB-Gyn (47.6% vs. 26.3%), and more OB-Gyn participants reported being unclear about the appropriate dosage of metformin for patients with obesity and PCOS (8.9% vs. 1.6%).

Conclusion

Our survey identified knowledge gaps in metabolic screening for patients with obesity and PCOS and a disparity in the evaluation and treatment of obesity in PCOS among different specialties. Similarly, it highlights the need to improve obesity management education for physicians caring for women with PCOS.
“What are we doing to our babies’ teeth?” Barriers to establishing oral health practices for Indigenous children in South Australia
Authors: Poirier Brianna , Hedges Joanne , Smithers Lisa , Moskos Megan , Jamieson Lisa
Published: September 2021

Background

During the 1970s, optimal oral health was experienced more frequently amongst Indigenous children in Australia than their non-Indigenous counterparts. As a result of public health interventions targeting oral disease, oral health has improved for most children; however, Indigenous children today experience oral disease at alarmingly high rates. A history of colonisation, assimilation, racism and cultural annihilation has had profound impacts on oral health for Indigenous peoples; compounded by environmental dispossession and a shift from traditional diets to one of processed and nutrient-poor foods, often high in sugar.

Methods

This project aimed to identify factors related to the increased occurrence of caries in Indigenous children. Using purposive sampling from the larger project, this paper thematically analyses 327 motivational interviews to explore current barriers impeding parental efforts to establish oral health and nutrition practices for Indigenous children. Representation of socioeconomic positions of families were compared across themes, as based on maternal age, employment, residency and number of children in care.

Results

Findings resulted in a conceptual model of barriers that exist across knowledge, social, structural and parental factors. Major thematic results include: social consumption of processed foods, busy households, misleading nutrition marketing, sugar cravings and lack of oral health and nutrition knowledge.

Conclusion

A discussion of the findings results in the following recommendations increased oral health promotion efforts in non-metropolitan areas; utilisation of community experiences in creating strategies that encourage oral health and nutrition knowledge; and the extension of oral health initiatives and future research to include all family members.

Trial registration Australian New Zealand Clinical Trial Registry ACTRN12611000111976; registered 01/02/2011.
SIESTA: a quick interprofessional learning activity fostering collaboration and communication between paediatric nursing trainees and medical students
Authors: Friedrich Sebastian , Straub Christine , Bode Sebastian Felix Nepomuk , Heinzmann Andrea
Published: September 2021

Background

Interprofessional education has emerged as a key concept in education of health professionals over the last 20 years. Positive effects of interprofessional education have been shown, but it has proved to be more time-consuming than traditional teaching methods. We therefore developed a 30-minute interprofessional learning activity, using peer-teaching methods. We were interested in effects on and ways of interprofessional learning, including conditions and resources that make it successful despite limited time.

Methods

Speed InterprofESsional Peer Teaching PaediAtric (SIESTA) was developed in the context of an interprofessional training ward. 20 paediatric nursing trainees and 20 medical students were enrolled in the study. Two students from each profession participated in a total of four SIESTA sessions each, supervised by registered paediatric nurses and paediatricians. We used a mixed-methods approach of quantitative and qualitative data (questionnaires, semi-guided focus group interviews) to evaluate self-perceived interprofessional competencies, interprofessional learning gains and ways of interprofessional learning.

Results

Questionnaires were obtained from all participants (n = 40) and n = 26 took part in the group interviews. Participants from both professions reported an increase in self-perceived understanding of interprofessional roles and tasks. Communication and cooperation emerged as important aspects. The workplace-based nature of SIESTA promoted interprofessional learning, while peer teaching fostered a safe learning environment. Regarding time constraints participants suggested thorough preparation and structuring by facilitators as a solution.

Conclusions

Our short interprofessional peer teaching activity showed promising results. Participants reported enhanced interprofessional competencies and provided suggestions for successful learning in limited time. Further studies should include an objective assessment of the interprofessional learning progress. The SIESTA concept can be easily adapted to other medical fields, providing interprofessional learning opportunities for many more health care professionals to come.
Burdens, resources, health and wellbeing of nurses working in general and specialised palliative care in Germany – results of a nationwide cross-sectional survey study
Authors: Diehl Elisabeth , Rieger Sandra , Letzel Stephan , Schablon Anja , Nienhaus Albert , Escobar Pinzon Luis Carlos , Dietz Pavel
Published: September 2021

Background

Palliative care in Germany is divided into general (GPC) and specialised palliative care (SPC). Although palliative care will become more important in the care sector in future, there is a large knowledge gab, especially with regard to GPC. The aim of this study was to identify and compare the burdens, resources, health and wellbeing of nurses working in GPC and SPC. Such information will be helpful for developing prevention programs in order to reduce burdens and to strengthen resources of nurses.

Methods

In 2017, a nationwide cross-sectional survey was conducted. In total, 437 nurses in GPC and 1316 nurses in SPC completed a questionnaire containing parts of standardised instruments, which included parts of the Copenhagen Psychosocial Questionnaire (COPSOQ), the Patient Health Questionnaire (PHQ-2), the Resilience Scale (RS-13) Questionnaire, a single question about back pain from the health survey conducted by the Robert Koch Institute as well as self-developed questions. The differences in the variables between GPC and SPC nurses were compared.

Results

SPC nurses reported higher emotional demands as well as higher burdens due to nursing care and the care of relatives while GPC nurses stated higher quantitative demands, i.e. higher workload. SPC nurses more often reported organisational and social resources that were helpful in dealing with the demands of their work. Regarding health, GPC nurses stated a poorer health status and reported chronic back pain as well as a major depressive disorder more frequently than SPC nurses. Furthermore, GPC nurses reported a higher intention to leave the profession compared to SPC nurses.

Conclusions

The findings of the present study indicate that SPC could be reviewed as the best practice example for nursing care in Germany. The results may be used for developing target group specific prevention programs for improving health and wellbeing of nurses taking the differences between GPC and SPC into account. Finally, interventional and longitudinal studies should be conducted in future to determine causality in the relationship of burdens, resources, health and wellbeing.
The iSplit GFP assay detects intracellular recombinant proteins in Bacillus subtilis
Authors: Lenz Patrick , Hilgers Fabienne , Burmeister Alina , Zimmermann Leonie , Volkenborn Kristina , Grünberger Alexander , Kohlheyer Dietrich , Drepper Thomas , Jaeger Karl-Erich , Knapp Andreas
Published: September 2021

Background

Bacillus subtilisis one of the most important microorganisms for recombinant protein production. It possesses the GRAS (generally recognized as safe) status and a potent protein secretion capacity. Secretory protein production greatly facilitates downstream processing and thus significantly reduces costs. However, not all heterologous proteins are secreted and intracellular production poses difficulties for quantification. To tackle this problem, we have established a so-called intracellular split GFP (iSplit GFP) assay inB. subtilisas a tool for the in vivo protein detection during expression in batch cultures and at a single-cell level. For the iSplit GFP assay, the eleventh β-sheet ofsfGFP is fused to a target protein and can complement a detector protein consisting of the respective truncatedsfGFP (GFP1-10) to form fluorescent holo-GFP.

Results

As proof of concept, the GFP11-tag was fused C-terminally to theE. coliβ-glucuronidase GUS, resulting in fusion protein GUS11. Variable GUS and GUS11 production levels inB. subtiliswere achieved by varying the ribosome binding site via spacers of increasing lengths (4–12 nucleotides) for the GUS-encoding gene. Differences in intracellular enzyme accumulation were determined by measuring the GUS11 enzymatic activity and subsequently by adding the detector protein to respective cell extracts. Moreover, the detector protein was co-produced with the GUS11 using a two-plasmid system, which enabled the in vivo detection and online monitoring of glucuronidase production. Using this system in combination with flow cytometry and microfluidics, we were able to monitor protein production at a single-cell level thus yielding information about intracellular protein distribution and culture heterogeneity.

Conclusion

Our results demonstrate that the iSplit GFP assay is suitable for the detection, quantification and online monitoring of recombinant protein production inB. subtilisduring cultivation as well as for analyzing production heterogeneity and intracellular localization at a single-cell level.

Graphic abstract
Combining malaria vaccination with chemoprevention: a promising new approach to malaria control
Authors: Greenwood Brian , Cairns Matthew , Chaponda Mike , Chico R. Matthew , Dicko Alassane , Ouedraogo Jean-Bosco , Phiri Kamija S. , ter Kuile Feiko O. , Chandramohan Daniel
Published: September 2021

Malaria control has stalled in a number of African countries and novel approaches to malaria control are needed for these areas. The encouraging results of a recent trial conducted in young children in Burkina Faso and Mali in which a combination of the RTS,S/AS01Emalaria vaccine and seasonal malaria chemoprevention led to a substantial reduction in clinical cases of malaria, severe malaria, and malaria deaths compared with the administration of either intervention given alone suggests that there may be other epidemiological/clinical situations in which a combination of malaria vaccination and chemoprevention could be beneficial. Some of these potential opportunities are considered in this paper. These include combining vaccination with intermittent preventive treatment of malaria in infants, with intermittent preventive treatment of malaria in pregnancy (through vaccination of women of child-bearing age before or during pregnancy), or with post-discharge malaria chemoprevention in the management of children recently admitted to hospital with severe anaemia. Other potential uses of the combination are prevention of malaria in children at particular risk from the adverse effects of clinical malaria, such as those with sickle cell disease, and during the final stages of a malaria elimination programme when vaccination could be combined with repeated rounds of mass drug administration. The combination of a pre-erythrocytic stage malaria vaccine with an effective chemopreventive regimen could make a valuable contribution to malaria control and elimination in a variety of clinical or epidemiological situations, and the potential of this approach to malaria control needs to be explored.
From the factory to the field: considerations of product characteristics for insecticide-treated net (ITN) bioefficacy testing
Authors: Skovmand Ole , Dang Duoc M. , Tran Trung Q. , Bossellman Rune , Moore Sarah J.
Published: September 2021

Background

Insecticide-treated nets (ITNs) undergo a series of tests to obtain listing by World Health Organization (WHO) Prequalification. These tests characterize the bioefficacy, physical and chemical properties of the ITN. ITN procurers assume that product specifications relate to product performance. Here, ITN test methods and their underlying assumptions are discussed from the perspective of the ITN manufacturing process and product characteristics.

Methods

Data were extracted from WHO Pesticide Evaluation Scheme (WHOPES) meeting reports from 2003 to 2017, supplemented with additional chemical analysis to critically evaluate ITNs bioassays with a focus on sampling, washing and wash resistance, and bioefficacy testing. Production methods for ITNs and their impact on testing outcomes are described.

Results and recommendations

ITNs are not homogenous products. They vary within panels and between the sides and the roof. Running tests of wash resistance using a before/after tests on the same sample or band within a net reduces test variability. As mosquitoes frequently interact with ITN roofs, additional sampling of the roof when evaluating ITNs is advisable because in nets where roof and sides are of the same material, the contribution of roof sample (20–25%) to the average is less than the tolerance for the specification (25%). Mosquito mortality data cannot be reliably used to evaluate net surface concentration to determine regeneration time (RT) and resistance to washing as nets may regenerate beyond the insecticide concentrations needed to kill 100% of susceptible mosquitoes. Chemical assays to quantify surface concentration are needed. The Wash Resistance Index (WRI) averaged over the first four washes is only informative if the product has a log linear loss rate of insecticide. Using a WRI that excludes the first wash off gives more reliable results. Storage conditions used for product specifications are lower than those encountered under product shipping and storage that may exceed 50 °C, and should be reconsidered. Operational monitoring of new ITNs and linking observed product performance, such as bioefficacy after 2 or 3 years of use, with product characteristics, such as WRI, will aid the development of more robust test methods and product specifications for new products coming to market.
Mithramycin delivery systems to develop effective therapies in sarcomas
Authors: Estupiñán Óscar , Niza Enrique , Bravo Iván , Rey Verónica , Tornín Juan , Gallego Borja , Clemente-Casares Pilar , Moris Francisco , Ocaña Alberto , Blanco-Lorenzo Verónica , Rodríguez-Santamaría Mar , Vallina-Álvarez Aitana , González M. Victoria , Rodríguez Aida , Hermida-Merino Daniel , Alonso-Moreno Carlos , Rodríguez René
Published: September 2021

Background

Sarcomas comprise a group of aggressive malignancies with very little treatment options beyond standard chemotherapy. Reposition of approved drugs represents an attractive approach to identify effective therapeutic compounds. One example is mithramycin (MTM), a natural antibiotic which has demonstrated a strong antitumour activity in several tumour types, including sarcomas. However, its widespread use in the clinic was limited by its poor toxicity profile.

Results

In order to improve the therapeutic index of MTM, we have loaded MTM into newly developed nanocarrier formulations. First, polylactide (PLA) polymeric nanoparticles (NPs) were generated by nanoprecipitation. Also, liposomes (LIP) were prepared by ethanol injection and evaporation solvent method. Finally, MTM-loaded hydrogels (HG) were obtained by passive loading using a urea derivative non-peptidic hydrogelator. MTM-loaded NPs and LIP display optimal hydrodynamic radii between 80 and 105 nm with a very low polydispersity index (PdI) and encapsulation efficiencies (EE) of 92 and 30%, respectively. All formulations show a high stability and different release rates ranging from a fast release in HG (100% after 30 min) to more sustained release from NPs (100% after 24 h) and LIP (40% after 48 h). In vitro assays confirmed that all assayed MTM formulations retain the cytotoxic, anti-invasive and anti-stemness potential of free MTM in models of myxoid liposarcoma, undifferentiated pleomorphic sarcoma and chondrosarcoma. In addition, whole genome transcriptomic analysis evidenced the ability of MTM, both free and encapsulated, to act as a multi-repressor of several tumour-promoting pathways at once. Importantly, the treatment of mice bearing sarcoma xenografts showed that encapsulated MTM exhibited enhanced therapeutic effects and was better tolerated than free MTM.

Conclusions

Overall, these novel formulations may represent an efficient and safer MTM-delivering alternative for sarcoma treatment.

Graphical abstract
Frequency of deep vein thrombosis at admission for acute stroke and associated factors: a cross-sectional study
Authors: Mori Takahisa , Yoshioka Kazuhiro , Tanno Yuhei
Published: September 2021

Background

Intermittent pneumatic compression (IPC) is commonly used to prevent deep vein thrombosis (DVT) during hospitalization in patients with acute stroke. However, if DVT exists at admission, IPC of the legs with DVT may cause migration of the thrombi, resulting in pulmonary emboli. Whole-leg ultrasonography (wl-US) is a practical tool to detect DVT; however, wl-US is not always performed at admission in all stroke patients. This retrospective cross-sectional study aimed to investigate DVT frequency and identify significant factors indicating the presence of DVT at admission for acute stroke.

Methods

We included patients admitted within 24 h of stroke onset between 2017 and 2019. Patients who did not undergo blood tests for D-dimer or wl-US within 72 h of arrival were excluded. We collected patient data on age; sex; anthropometric variables; presence of DVT on wl-US; and biomarkers such as D-dimer, high-sensitivity C-reactive protein (hs-CRP), and lipids.

Results

Of 1129 acute stroke patients, 917 met our inclusion criteria. DVT was detected in 161 patients (17.6 %). Patients with DVT were older; were more likely to be female; had lower body weight; had higher D-dimer and hs-CRP levels; had lower albumin, hemoglobin, and triglyceride levels; and had higher National Institutes of Health Stroke Scale and pre-stroke modified Rankin scale scores than patients without DVT (n = 756). In addition, multiple logistic regression analysis showed that sex (female) and D-dimer levels (≥ 1.52 µg/mL) were independent significant factors for the presence of DVT. Among 161 patients with DVT, 78 (48.4 %) had both these significant factors. Among 756 patients without DVT, 602 (79.6 %) had no or one significant factor. The odds ratio of the presence of DVT in patients with both significant factors was 6.29, using patients without any significant factors as the group for comparison.

Conclusions

The frequency of DVT is high in acute stroke patients at admission. Female sex and a high D-dimer level were independent significant factors for the presence of DVT. Therefore, in patients with these two significant factors at admission, IPC should be avoided or wl-US should be performed before IPC.
Coevolution of COVID-19 research and China’s policies
Authors: Cheng Xi , Tang Li , Zhou Maotian , Wang Guoyan
Published: September 2021

Background

In the era of evidence-based policy-making (EBPM), scientific outputs and public policy should engage with each other in a more interactive and coherent way. Notably, this is becoming increasingly critical in preparing for public health emergencies.

Methods

To explore the coevolution dynamics between science and policy (SAP), this study explored the changes in, and development of, COVID-19 research in the early period of the COVID-19 outbreak in China, from 30 December 2019 to 26 June 2020. In this study, VOSviewer was adopted to calculate the link strength of items extracted from scientific publications, and machine learning clustering analysis of scientific publications was carried out to explore dynamic trends in scientific research. Trends in relevant policies that corresponded to changing trends in scientific research were then traced.

Results

The study observes a salient change in research content as follows: an earlier focus on “children and pregnant patients”, “common symptoms”, “nucleic acid test”, and “non-Chinese medicine” was gradually replaced with a focus on “aged patients”, “pregnant patients”, “severe symptoms and asymptomatic infection”, “antibody assay”, and “Chinese medicine”. “Mental health” is persistent throughout China’s COVID-19 research. Further, our research reveals a correlation between the evolution of COVID-19 policies and the dynamic development of COVID-19 research. The average issuance time of relevant COVID-19 policies in China is 8.36 days after the launching of related research.

Conclusions

In the early stage of the outbreak in China, the formulation of research-driven-COVID-19 policies and related scientific research followed a similar dynamic trend, which is clearly a manifestation of a coevolution model (CEM). The results of this study apply more broadly to the formulation of policies during public health emergencies, and provide the foundation for future EBPM research.
Innate immune responses after stimulation with Toll-like receptor agonists in ex vivo microglial cultures and an in vivo model using mice with reduced microglia
Authors: Carroll James A. , Race Brent , Williams Katie , Striebel James F. , Chesebro Bruce
Published: September 2021

Background

Past experiments studying innate immunity in the central nervous system (CNS) utilized microglia obtained from neonatal mouse brain, which differ developmentally from adult microglia. These differences might impact our current understanding of the role of microglia in CNS development, function, and disease.

Methods

Cytokine protein secretion was compared in ex vivo P3 and adult microglial cultures after exposure to agonists for three different toll-like receptors (TLR4, lipopolysaccharide [LPS]; TLR7, imiquimod [IMQ]; and TLR9, CpG Oligodeoxynucleotide [CpG-ODN] 1585). In addition, changes in inflammatory gene expression in ex vivo adult microglia in response to the TLR agonists was assessed. Furthermore, in vivo experiments evaluated changes in gene expression associated with inflammation and TLR signaling in brains of mice with or without treatment with PLX5622 to reduce microglia.

Results

Ex vivo adult and P3 microglia increased cytokine secretion when exposed to TLR4 agonist LPS and to TLR7 agonist IMQ. However, adult microglia decreased expression of numerous genes after exposure to TLR 9 agonist CpG-ODN 1585. In contrast, in vivo studies indicated a core group of inflammatory and TLR signaling genes increased when each of the TLR agonists was introduced into the CNS. Reducing microglia in the brain led to decreased expression of various inflammatory and TLR signaling genes. Mice with reduced microglia showed extreme impairment in upregulation of genes after exposure to TLR7 agonist IMQ.

Conclusions

Cultured adult microglia were more reactive than P3 microglia to LPS or IMQ exposure. In vivo results indicated microglial influences on neuroinflammation were agonist specific, with responses to TLR7 agonist IMQ more dysregulated in mice with reduced microglia. Thus, TLR7-mediated innate immune responses in the CNS appeared more dependent on the presence of microglia. Furthermore, partial responses to TLR4 and TLR9 agonists in mice with reduced microglia suggested other cell types in the CNS can compensate for their absence.
Acute myocardial infarction associated with abacavir and tenofovir based antiretroviral drug combinations in the United States
Authors: Dorjee Kunchok , Desai Manisha , Choden Tsering , Baxi Sanjiv M. , Hubbard Alan E. , Reingold Arthur L.
Published: September 2021

Introduction

Although individual antiretroviral drugs have been shown to be associated with elevated cardiovascular disease (CVD) risk, data are limited on the role of antiretroviral drug combinations. Therefore, we sought to investigate CVD risk associated with antiretroviral drug combinations.

Methods

Using an administrative health-plan dataset, risk of acute myocardial infarction (AMI) associated with current exposure to antiretroviral drug combinations was assessed among persons living with HIV receiving antiretroviral therapy (ART) across the U.S. from October 2009 through December 2014. To account for confounding-by-indication and for factors simultaneously acting as causal mediators and confounders, we applied inverse probability of treatment weighted marginal structural models to longitudinal data of patients.

Results

Over 114,417 person-years (n = 73,071 persons) of ART exposure, 602 cases of AMI occurred at an event rate of 5.26 (95% CI: 4.86, 5.70)/1000 person-years. Of the 14 antiretroviral drug combinations studied, persons taking abacavir-lamivudine-darunavir had the highest incidence rate (IR: 11/1000; 95% CI: 7.4–16.0) of AMI. Risk (HR; 95% CI) of AMI was elevated for current exposure to abacavir-lamivudine-darunavir (1.91; 1.27–2.88), abacavir-lamivudine-atazanavir (1.58; 1.08–2.31), and tenofovir-emtricitabine-raltegravir (1.35; 1.07–1.71). Tenofovir-emtricitabine-efavirenz was associated with reduced risk (0.65; 0.54–0.78). Abacavir-lamivudine-darunavir was associated with increased risk of AMI beyond that expected of abacavir alone, likely attributable to darunavir co-administration. We did not find an elevated risk of AMI when abacavir-lamivudine was combined with efavirenz or raltegravir.

Conclusion

The antiretroviral drug combinations abacavir-lamivudine-darunavir, abacavir-lamivudine-atazanavir and tenofovir-emtricitabine-raltegravir were found to be associated with elevated risk of AMI, while tenofovir-emtricitabine-efavirenz was associated with a lower risk. The AMI risk associated with abacavir-lamivudine-darunavir was greater than what was previously described for abacavir, which could suggest an added risk from darunavir. The results should be confirmed in additional studies.
Do international trade and investment agreements generate regulatory chill in public health policymaking? A case study of nutrition and alcohol policy in South Africa
Authors: Milsom Penelope , Smith Richard , Modisenyane Simon Moeketsi , Walls Helen
Published: September 2021

Background

Trade and health scholars have raised concern that international trade and particularly investment disputes may be used by transnational health harmful commodity corporations (THCCs) to effectively generate public health regulatory chill. The purpose of this study was to contribute to the limited evidence base of trade or investment dispute-related regulatory chill using a case study of nutrition and alcohol policy in South Africa.

Methods

We conducted 35 semi-structured interviews with 36 key stakeholders involved in nutrition, alcohol and/or trade/investment policymaking in South Africa. Interview transcripts were analyzed using thematic analysis. We used Schram et al’s theory on three forms of regulatory chill (anticipatory, response and precedential) to guide the analysis. We report evidence on each form of regulatory chill as well as specific contextual factors that may influence the risk of regulatory chill.

Results

Trade obligations were found to generate a significantly greater anticipatory-type chilling effect on nutrition and alcohol regulation than South Africa’s investment treaty obligations. Response chill was reported to have occurred in relation to South Africa’s proposed tobacco plain packaging regulation while awaiting the outcome of both Australia’s investor-state and WTO state-state disputes. No cases were reported of THCCs threatening an investor-state dispute over nutrition or food regulations, but there were reported cases of THCCs using arguments related to South Africa’s trade obligations to oppose policy action in these areas. No evidence of nutrition or alcohol policy precedential chill were identified. Factors affecting the risk of policy chill include legitimacy and perceived bias of the dispute system, costs involved in pursuing a regulation/defending a dispute and capacity to pay, social acceptability of the industry, a product’s perceived risk to health and confidence in a successful dispute outcome e.g. through cross-border policy learning.

Conclusions

Our findings indicate that currently, South Africa’s trade obligations have a more prominent role in inhibiting nutrition and alcohol action than investment treaty-related concerns. However, given the potential for wider use of the ISDS mechanism by THCCs in the future, strategies to protect public health policy space in the context of both international trade and investment treaty and dispute settlement contexts remain important.
A cross-sectional study of lactation room quality and Dutch working mothers’ satisfaction, perceived ease of, and perceived support for breast milk expression at work
Authors: van Dellen Sjoukje A. , Wisse Barbara , Mobach Mark P. , Albers Casper J. , Dijkstra Arie
Published: September 2021

Background

The challenge of combining professional work and breastfeeding is a key reason why women choose not to breastfeed or to stop breastfeeding early. We posited that having access to a high-quality lactation room at the workplace could influence working mothers’ satisfaction and perceptions related to expressing breast milk at work, which could have important longer term consequences for the duration of breastfeeding. Specifically, we aimed to (1) develop a checklist for assessing the quality of lactation rooms and (2) explore how lactation room quality affects lactating mothers’ satisfaction and perceptions. Drawing on social ecological insights, we hypothesized that the quality of lactation rooms (operationalized as any space used for expressing milk at work) would be positively related to mothers’ satisfaction with the room, perceived ease of, and perceived support for milk expression at work.

Methods

We conducted two studies. In Study 1 we developed a lactation room quality checklist (LRQC) and assessed its reliability twice, using samples of 33 lactation rooms (Study 1a) and 31 lactation rooms (Study 1b). Data were collected in the Northern part of the Netherlands (between December 2016 and April 2017). Study 2 comprised a cross-sectional survey of 511 lactating mothers, working in a variety of Dutch organizations. The mothers were recruited through the Facebook page of a popular Dutch breastfeeding website. They completed online questionnaires containing the LRQC and measures aimed at assessing their satisfaction and perceptions related to milk expression at work (in June and July 2017).

Results

The LRQC was deemed reliable and easy to apply in practice. As predicted, we found that objectively assessed higher-quality lactation rooms were associated with increased levels of satisfaction with the lactation rooms, perceived ease of milk expression at work, and perceived support from supervisors and co-workers for expressing milk in the workplace.

Conclusions

The availability of a high-quality lactation room could influence mothers’ decisions regarding breast milk expression at work and the commencement and/or continuation of breastfeeding. Future studies should explore whether and how lactation room quality affects breastfeeding choices, and which aspects are most important to include in lactation rooms.
Wild-type FUS corrects ALS-like disease induced by cytoplasmic mutant FUS through autoregulation
Authors: Sanjuan-Ruiz Inmaculada , Govea-Perez Noé , McAlonis-Downes Melissa , Dieterle Stéphane , Megat Salim , Dirrig-Grosch Sylvie , Picchiarelli Gina , Piol Diana , Zhu Qiang , Myers Brian , Lee Chao-Zong , Cleveland Don W , Lagier-Tourenne Clotilde , Da Cruz Sandrine , Dupuis Luc
Published: September 2021

Mutations in FUS, an RNA-binding protein involved in multiple steps of RNA metabolism, are associated with the most severe forms of amyotrophic lateral sclerosis (ALS). Accumulation of cytoplasmic FUS is likely to be a major culprit in the toxicity ofFUSmutations. Thus, preventing cytoplasmic mislocalization of the FUS protein may represent a valuable therapeutic strategy. FUS binds to its own pre-mRNA creating an autoregulatory loop efficiently buffering FUS excess through multiple proposed mechanisms including retention of introns 6 and/or 7. Here, we introduced a wild-typeFUSgene allele, retaining all intronic sequences, in mice whose heterozygous or homozygous expression of a cytoplasmically retained FUS protein (Fus∆NLS) was previously shown to provoke ALS-like disease or postnatal lethality, respectively. Wild-type FUS completely rescued the early lethality caused by the twoFus∆NLSalleles, and improved the age-dependent motor deficits and reduced lifespan caused by heterozygous expression of mutant FUS∆NLS. Mechanistically, wild-type FUS decreased the load of cytoplasmic FUS, increased retention of introns 6 and 7 in the endogenous mouseFusmRNA, and decreased expression of the mutant mRNA. Thus, the wild-typeFUSallele activates the homeostatic autoregulatory loop, maintaining constant FUS levels and decreasing the mutant protein in the cytoplasm. These results provide proof of concept that an autoregulatory competent wild-type FUS expression could protect against this devastating, currently intractable, neurodegenerative disease.
APOΕ4 lowers energy expenditure in females and impairs glucose oxidation by increasing flux through aerobic glycolysis
Authors: Farmer Brandon C. , Williams Holden C. , Devanney Nicholas A. , Piron Margaret A. , Nation Grant K. , Carter David J. , Walsh Adeline E. , Khanal Rebika , Young Lyndsay E. A. , Kluemper Jude C. , Hernandez Gabriela , Allenger Elizabeth J. , Mooney Rachel , Golden Lesley R. , Smith Cathryn T. , Brandon J. Anthony , Gupta Vedant A. , Kern Philip A. , Gentry Matthew S. , Morganti Josh M. , Sun Ramon C. , Johnson Lance A.
Published: September 2021

Background

Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer’s disease (AD), as well as in young cognitively normal carriers of the Ε4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field.

Methods

Here, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4.

Results

Single-cell analysis of brain tissue from mice expressing human APOE revealed E4-associated decreases in genes related to oxidative phosphorylation, particularly in astrocytes. This shift was confirmed on a metabolic level with isotopic tracing of 13C-glucose in E4 mice and astrocytes, which showed decreased pyruvate entry into the TCA cycle and increased lactate synthesis. Metabolic phenotyping of E4 astrocytes showed elevated glycolytic activity, decreased oxygen consumption, blunted oxidative flexibility, and a lower rate of glucose oxidation in the presence of lactate. Together, these cellular findings suggest an E4-associated increase in aerobic glycolysis (i.e. the Warburg effect). To test whether this phenomenon translated to APOE4 humans, we analyzed the plasma metabolome of young and middle-aged human participants with and without the Ε4 allele, and used indirect calorimetry to measure whole body oxygen consumption and energy expenditure. In line with data from E4-expressing female mice, a subgroup analysis revealed that young female E4 carriers showed a striking decrease in energy expenditure compared to non-carriers. This decrease in energy expenditure was primarily driven by a lower rate of oxygen consumption, and was exaggerated following a dietary glucose challenge. Further, the stunted oxygen consumption was accompanied by markedly increased lactate in the plasma of E4 carriers, and a pathway analysis of the plasma metabolome suggested an increase in aerobic glycolysis.

Conclusions

Together, these results suggest astrocyte, brain and system-level metabolic reprogramming in the presence of APOE4, a ‘Warburg like’ endophenotype that is observable in young females decades prior to clinically manifest AD.
Protein degradation technology: a strategic paradigm shift in drug discovery
Authors: Li Haobin , Dong Jinyun , Cai Maohua , Xu Zhiyuan , Cheng Xiang-Dong , Qin Jiang-Jiang
Published: September 2021

Targeting pathogenic proteins with small-molecule inhibitors (SMIs) has become a widely used strategy for treating malignant tumors. However, most intracellular proteins have been proven to be undruggable due to a lack of active sites, leading to a significant challenge in the design and development of SMIs. In recent years, the proteolysis-targeting chimeric technology and related emerging degradation technologies have provided additional approaches for targeting these undruggable proteins. These degradation technologies show a tendency of superiority over SMIs, including the rapid and continuous target consumption as well as the stronger pharmacological effects, being a hot topic in current research. This review mainly focuses on summarizing the development of protein degradation technologies in recent years. Their advantages, potential applications, and limitations are also discussed. We hope this review would shed light on the design, discovery, and clinical application of drugs associated with these degradation technologies.
Delayed pubarche
Authors: Baldo Francesco , Barbi Egidio , Tornese Gianluca
Published: September 2021

In healthy adolescents, delayed pubarche is generally a benign condition that is caused by a physiological discrepancy between gonadarche and adrenarche. In presence of other clinical signs and symptoms, delayed pubarche can be caused by single or multiple hormones deficiency (such as adrenal insufficiency, panhypopituitarism and hypothyroidism) and/or genetic conditions (Turner syndrome, androgen insensitivity syndrome). Exposition to endocrine disruptors has also been described as a possible cause of delay of pubic hair development. Basic blood tests, karyotype and first level imaging studies are helpful in the differential diagnosis.
Acupuncture for combat post-traumatic stress disorder: trial development and methodological approach for a randomized controlled clinical trial
Authors: Hollifield Michael , Hsiao An-Fu , Carrick Kala , Gory Munoz Andrea , Calloway Teresa , Cocozza Karen , Smith Besa , Smith Tyler , Jovanovic Tanja , Norrholm Seth , Sokhadze Estate , Reist Christopher
Published: September 2021

Background

Post-traumatic stress disorder (PTSD) is a significant public health problem, affecting approximately 7% of the general population and 13–18% of the combat Veteran population. The first study using acupuncture for PTSD in a civilian population showed large pre- to post-treatment effects for an empirically developed verum protocol, which was equivalent to group cognitive behavior therapy and superior to a wait-list control. The primary objective of this study is to determine both clinical and biological effects of verum acupuncture for combat-related PTSD in treatment-seeking US Veterans.

Methods

This is a two-arm, parallel-group, prospective randomized placebo-controlled clinical trial. The experimental condition is verum acupuncture and the placebo control is sham (minimal) acupuncture in 1-h sessions, twice a week for 12 weeks. Ninety subjects will provide adequate power and will be allocated to group by an adaptive randomization procedure. The primary outcome is change in PTSD symptom severity from pre- to post-treatment. The secondary biological outcome is change from pre- to post-treatment in psychophysiological response, startle by electromyographic (EMG) eyeblink. Assessments will be conducted at pre-, mid-, post-, and 1-month post-treatment, blind to group allocation. Intent-to-treat analyses will be conducted.

Discussion

The study results will be definitive because both clinical and biological outcomes will be assessed and correlated. Issues such as the number needed for recruitment and improvement, use of sham acupuncture, choice of biological measure, and future research need will be discussed.

Trial registration

ClinicalTrials.gov NCT02869646. Registered on 17 August 2016.