bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated with SARS-CoV2 infection and care pathways among the most vulnerable populations living in Marseille: a case control study
Authors: Alsaïdi Ismaïl , De Sousa Santos Frédéric , Plard Bérengère , Janvier Elise , Tinland Aurélie , Hafni Abdelmajid , Mosnier Emilie
Published: September 2021

Background

The Covid-19 pandemic has led to substantial and unexpected increases in morbidity and mortality in France. Vulnerable populations housed in accommodation centres have a greater risk of infection because collective housing and their dependence on social support services mean it is more difficult to apply preventive measures. They are also at greater risk of developing severe forms of Covid-19 and waiting longer before seeking healthcare (for Covid-19 or other) treatment. We aimed to identify the factors associated with SARS-CoV2 infection in the most vulnerable populations in the city of Marseille.

Methods

The study sample comprised users of various services provided by the association AAJT in Marseille, France, some presenting symptoms suggestive of Covid-19 and others not. All had routine health surveillance provided by AAJT’s dedicated healthcare team between March 2020 and May 2020. Using univariate and multivariate analyses, we studied the influence of several variables on morbidity associated with Covid-19.

Results

The study included 64 participants, 29 of whom tested positive for Covid-19 and 35 control subjects. Median age was 21.16 years old. Individuals in the ‘Covid-19 case’ group (p < 0.005) – which included persons testing positive and those suspected of being infected – were younger. The study sample’s male/female ratio was seven. In our multivariate analyses, living in a shared apartment and poor adherence to social distancing measures were factors associated with Covid-19 infection. Furthermore, mental health problems - such as anxiety disorder - were very frequent in the study sample.

Conclusions

Allocating more and specific housing units to structures providing accommodation services to the most vulnerable people would seem to be a decisive factor in controlling the spread of SARS-CoV2, and deserves more attention from public authorities.
A review of the inclusion of equity stratifiers for the measurement of health inequalities within health and social care data collections in Ireland
Authors: Carroll Christopher , Evans Katie , Elmusharaf Khalifa , O’Donnell Patrick , Dee Anne , O’Donovan Diarmuid , Casey Marie
Published: September 2021

Background

Health equity differs from the concept of health inequality by taking into consideration the fairness of an inequality. Inequities may be culturally specific, based on social relations within a society. Measuring these inequities often requires grouping individuals. These groupings can be termed equity stratifiers. The most common groupings affected by health inequalities are summarised by the acronym PROGRESS (Place of residence, Race, Occupation, Gender, Religion, Education, Socioeconomic status, Social capital). The aim of this review was to examine the use of equity stratifiers in routinely collected health and social care data collections in Ireland.

Methods

One hundred and twenty data collections were identified from the Health Information and Quality Authority (HIQA) document, “Catalogue of national health and social care data collections: Version 3.0”. Managers of all the data collections included were contacted and a data dictionary was requested where one was not available via the HIQA website. Each of the data dictionaries available was reviewed to identify the equity stratifiers recorded.

Results

Eighty-three of the 120 data collections were considered eligible to be included for review. Twenty-nine data dictionaries were made available. There was neither a data dictionary available nor a response to our query from data collection managers for twenty-three (27.7%) of the data collections eligible for inclusion. Data dictionaries were from national data collections, regional data collections and national surveys. All data dictionaries contained at least one of the PROGRESS equity stratifiers. National surveys included more equity stratifiers compared with national and regional data collections. Definitions used for recording social groups for the stratifiers examined lacked consistency.

Conclusions

While there has been much discussion on tackling health inequalities in Ireland in recent years, health and social care data collections do not always record the social groupings that are most commonly affected. In order to address this, it is necessary to consider which equity stratifiers should be used for the Irish population and, subsequently, for agreed stratifiers to be incorporated into routine health data collection. These are lessons that can be shared internationally as other countries begin to address deficits in their use of equity stratifiers.
Association between self-control and health risk behaviors: a cross-sectional study with 9th grade adolescents in São Paulo
Authors: Astolfi Roberta Corradi , Leite Maria Alvim , Papa Cassio Henrique Gomide , Ryngelblum Marcelo , Eisner Manuel , Peres Maria Fernanda Tourinho
Published: September 2021

Background

Self-control (SC) has been consistently found associated with diverse health risk behaviors (HRBs), but little research refers to low- and middle-income countries. Furthermore, there is evidence that some HRBs tend to aggregate, however studies with the specific purpose of addressing the relation between SC and multiple health risk behaviors (MHRBs) are rare. The objective of this study is to analyze these associations and provide evidence to help filling these gaps.

Methods

A sample of 2106 9th grade students from the city of São Paulo responded a self-administered questionnaire in 2017. We tested the association of SC measured as an ordinal variable with four levels (higher, high, medium and low) with six HRBs (binge drinking, marijuana use, smoking, high consumption of ultra-processed food, sedentary behavior and bullying perpetration), in both separated and aggregated forms (MHRBs), controlling for potential confounders. Binary logistic regression was used to test the association between exposure (SC) and single outcomes. In order to analyze the association of SC with MHRBs, multinomial logistic regression was employed.

Results

SC was associated with five of six HRBs investigated and with MHRBs. The effect size of the association of SC and MHRBs increased in a steep pattern with accumulation of more HRBs.

Conclusion

Low self-control is associated with most HRBs investigated and the magnitude of the association increases when more than two or three HRBs are accumulated. There seems to be a group of adolescents in a position of pronounced vulnerability for MHRBs. This should be considered when designing public policy and prevention programs. In contexts of limited or scarce resources and public funds, interventions focusing the most vulnerable groups, instead of universal interventions, should be considered.
Low socioeconomic position is a risk factor for delay to treatment and mortality of testicular cancer patients in Hungary, a prospective study
Authors: Küronya Zsófia , Fröhlich Georgina , Ladányi Andrea , Martin Tamás , Géczi Lajos , Gyergyai Fruzsina , Horváth Orsolya , Kiszner Gergő , Kovács Ágnes , Dienes Tamás , Lénárt Enikő , Nagyiványi Krisztián , Szarvas Tibor , Szőnyi Mihály , Tóth Attila , Biró Krisztina
Published: September 2021

Background

In Hungary, the mortality rate for testicular germ cell cancer (TGCC) is 0,9/100000 which is significantly higher than the EU average. We prospectively evaluated the effect of socioeconomic position on patient delay and therapy outcomes.

Methods

Questionnaires on subjective social status (MacArthur Subjective Status Scale), objective socioeconomic position (wealth, education, and housing data), and on patient’s delay were completed by newly diagnosed TGCC patients.

Results

Patients belonged to a relatively high socioeconomic class, a university degree was double the Hungarian average, Cancer-specific mortality in the highest social quartile was 1.56% while in the lowest social quartile 13.09% (p = 0.02). In terms of patient delay, 57.2% of deceased patients waited more than a year before seeking help, while this number for the surviving patients was 8.0% (p = 0.0000). Longer patient delay was associated with a more advanced stage in non-seminoma but not in seminoma, the correlation coefficient for non-seminoma was 0.321 (p < 0.001). For patient delay, the most important variables were the mother’s and patient’s education levels (r = − 0.21, p = 0.0003, and r = − 0.20, p = 0.0005), respectively. Since the patient delay was correlated with the social quartile and resulted in a more advanced stage in non-seminoma, the lower social quartile resulted in higher mortality in non-seminoma patients (p = 0.005) but not in seminoma patients (p = 0.36) where the patient delay was not associated with a more advanced stage.

Conclusions

Based on our result, we conclude that to improve survival, we should promote testicular cancer awareness, especially among the most deprived populations, and their health care providers.
Who declines to respond to the reactions to race module?: findings from the South Carolina Behavioral Risk Factor Surveillance System, 2016–2017
Authors: Srivastav Aditi , Robinson-Ector Kaitlynn , Kipp Colby , Strompolis Melissa , White Kellee
Published: September 2021

Background

The inclusion of self-reported differential treatment by race/ethnicity in population-based public health surveillance and monitoring systems may provide an opportunity to address long-standing health inequalities. While there is a growing trend towards decreasing response rates and selective non-response in health surveys, research examining the magnitude of non-response related to self-reported discrimination warrants greater attention. This study examined the distribution of sociodemographic variables among respondents and non-respondents to the South Carolina Behavioral Risk Factor Surveillance System (SC-BRFSS) Reactions to Race module (6-question optional module capturing reports of race-based treatment).

Methods

Using data from SC-BRFSS (2016, 2017), we examined patterns of non-response to the Reactions to Race module and individual items in the module. Logistic regression models were employed to examine sociodemographic factors associated with non-response and weighted to account for complex sampling design.

Results

Among 21,847 respondents, 15.3% were non-responders. Significant differences in RTRM non-response were observed by key sociodemographic variables (e.g., age, race/ethnicity, labor market participation, and health insurance status). Individuals who were younger, Hispanic, homemakers/students, unreported income, and uninsured were over-represented among non-respondents. In adjusted analyses, Hispanics and individuals with unreported income were more likely to be non-responders in RTRM and across item, while retirees were less likely to be non-responders. Heterogeneity in levels of non-responses were observed across RTRM questions, with the highest level of non-response for questions assessing differential treatment in work (54.8%) and healthcare settings (26.9%).

Conclusions

Non-responders differed from responders according to some key sociodemographic variables, which could contribute to the underestimation of self-reported discrimination and race-related differential treatment and health outcomes. While we advocate for the use of population-based measures of self-reported racial discrimination to monitor and track state-level progress towards health equity, future efforts to estimate, assess, and address non-response variations by sociodemographic factors are warranted to improve understanding of lived experiences impacted by race-based differential treatment.
Evaluation of the impact of childhood 13-valent pneumococcal conjugate vaccine introduction on adult pneumonia in Ulaanbaatar, Mongolia: study protocol for an observational study
Authors: von Mollendorf Claire , Ulziibayar Mukhchuluun , Gessner Bradford D. , Do Lien Anh Ha , Nguyen Cattram D. , Beavon Rohini , Suuri Bujinlkham , Luvsantseren Dashtseren , Narangerel Dorj , Jenney Adam , Dunne Eileen M. , Satzke Catherine , Darmaa Badarchiin , Mungun Tuya , Mulholland E. Kim
Published: September 2021

Background

Community-acquired pneumonia is an important cause of morbidity and mortality in adults. Approximately one-third of pneumonia cases can be attributed to the pneumococcus. Pneumococcal conjugate vaccines (PCVs) protect against colonisation with vaccine-type serotypes. The resulting decrease in transmission of vaccine serotypes leads to large indirect effects. There are limited data from developing countries demonstrating the impact of childhood PCV immunisation on adult pneumonia. There are also insufficient data available on the burden and severity of all-cause pneumonia and respiratory syncytial virus (RSV) in adults from low resource countries. There is currently no recommendation for adult pneumococcal vaccination with either pneumococcal polysaccharide vaccine or PCVs in Mongolia. We describe the protocol developed to evaluate the association between childhood 13-valent PCV (PCV13) vaccination and trends in adult pneumonia.

Methods

PCV13 was introduced into the routine childhood immunisation schedule in Mongolia in a phased manner from 2016. In March 2019 we initiated active hospital-based surveillance for adult pneumonia, with the primary objective of evaluating trends in severe hospitalised clinical pneumonia incidence in adults 18 years and older in four districts of Ulaanbaatar. Secondary objectives include measuring the association between PCV13 introduction and trends in all clinically-defined pneumonia, radiologically-confirmed pneumonia, nasopharyngeal carriage of S. pneumoniae and pneumonia associated with RSV or influenza. Clinical questionnaires, nasopharyngeal swabs, urine samples and chest radiographs were collected from enrolled patients. Retrospective administrative and clinical data were collected for all respiratory disease-related admissions from January 2015 to February 2019.

Discussion

Establishing a robust adult surveillance system may be an important component of monitoring the indirect impact of PCVs within a country. Monitoring indirect impact of childhood PCV13 vaccination on adult pneumonia provides additional data on the full public health impact of the vaccine, which has implications for vaccine efficiency and cost-effectiveness. Adult surveillance in Mongolia will contribute to the limited evidence available on the burden of pneumococcal pneumonia among adults in low- and middle-income countries, particularly in the Asia-Pacific region. In addition, it is one of the few examples of implementing prospective, population-based pneumonia surveillance to evaluate the indirect impact of PCVs in a resource-limited setting.
Health care utilization and health-related quality of life of injury patients: comparison of educational groups
Authors: van der Vlegel Marjolein , Spronk Inge , Oude Groeniger Joost , Toet Hidde , Panneman Martien J. M. , Polinder Suzanne , Haagsma Juanita A.
Published: September 2021

Background

Differences in health care utilization by educational level can contribute to inequalities in health. Understanding health care utilization and health-related quality of life (HRQoL) of educational groups may provide important insights into the presence of these inequalities. Therefore, we assessed characteristics, health care utilization and HRQoL of injury patients by educational level.

Method

Data for this registry based cohort study were extracted from the Dutch Injury Surveillance System. At 6-month follow-up, a stratified sample of patients (≥25 years) with an unintentional injury reported their health care utilization since discharge and completed the EQ-5-Dimension, 5-Level (EQ-5D-5L) and visual analogue scale (EQ VAS). Logistic regression analyses, adjusting for patient and injury characteristics, were performed to investigate the association between educational level and health care utilization. Descriptive statistics were used to analyse HRQoL scores by educational level, for hospitalized and non-hospitalized patients.

Results

This study included 2606 patients; 47.9% had a low, 24.4% a middle level, and 27.7% a high level of education. Patients with low education were more often female, were older, had more comorbidities, and lived more often alone compared to patients with high education (p < 0.001). Patients with high education were more likely to visit a general practitioner (OR: 1.38; CI: 1.11–1.72) but less likely to be hospitalized (OR: 0.79; CI: 0.63–1.00) and to have nursing care at home (OR: 0.66; CI: 0.49–0.90) compared to their low educated counterparts. For both hospitalized an non-hospitalized persons, those with low educational level reported lower HRQoL and more problems on all dimensions than those with a higher educational level.

Conclusion

Post-discharge, level of education was associated with visiting the general practitioner and nursing care at home, but not significantly with use of other health care services in the 6 months post-injury. Additionally, patients with a low educational level had a poorer HRQoL. However, other factors including age and sex may also explain a part of these differences between educational groups. It is important that patients are aware of potential consequences of their trauma and when and why they should consult a specific health care service after ED or hospital discharge.
Population genetic analysis of the Plasmodium falciparum erythrocyte binding antigen-175 (EBA-175) gene in Equatorial Guinea
Authors: Yang Pei-Kui , Liang Xue-Yan , Lin Min , Chen Jiang-Tao , Huang Hui-Ying , Lin Li-Yun , Ehapo Carlos Salas , Eyi Urbano Monsuy , Zheng Yu-Zhong , Xie Dong-De , He Jin-Quan , Mo Huan-Tong , Chen Xin-Yao , Liu Xiang-Zhi , Wu Ying-E.
Published: September 2021

Background

Plasmodium falciparum erythrocyte binding antigen-175 (PfEBA-175) is a candidate antigen for a blood-stage malaria vaccine, while various polymorphisms and dimorphism have prevented to development of effective vaccines based on this gene. This study aimed to investigate the dimorphism of PfEBA-175 on both the Bioko Island and continent of Equatorial Guinea, as well as the genetic polymorphism and natural selection of global PfEBA-175.

Methods

The allelic dimorphism of PfEBA-175 region II of 297 bloods samples from Equatorial Guinea in 2018 and 2019 were investigated by nested polymerase chain reaction and sequencing. Polymorphic characteristics and the effect of natural selection were analyzed using MEGA 7.0, DnaSP 6.0 and PopART programs. Protein function prediction of new amino acid mutation sites was performed using PolyPhen-2 and Foldx program.

Results

Both Bioko Island and Bata district populations, the frequency of the F-fragment was higher than that of the C-fragment of PfEBA-175 gene. The PfEBA-175 of Bioko Island and Bata district isolates showed a high degree of genetic variability and heterogeneity, with π values of 0.00407 & 0.00411 and Hd values of 0.958 & 0.976 for nucleotide diversity, respectively. The values of Tajima's D of PfEBA-175 on Bata district and Bioko Island were 0.56395 and − 0.27018, respectively. Globally, PfEBA-175 isolates from Asia were more diverse than those from Africa and South America, and genetic differentiation quantified by the fixation index between Asian and South American countries populations was significant (FST > 0.15, P < 0.05). A total of 310 global isolates clustered in 92 haplotypes, and only one cluster contained isolates from three continents. The mutations A34T, K109E, D278Y, K301N, L305V and D329N were predicted as probably damaging.

Conclusions

This study demonstrated that the dimorphism of F-fragment PfEBA-175 was remarkably predominant in the study area. The distribution patterns and genetic diversity of PfEBA-175 in Equatorial Guinea isolates were similar another region isolates. And the levels of recombination events suggested that natural selection and intragenic recombination might be the main drivers of genetic diversity in global PfEBA-175. These results have important reference value for the development of blood-stage malaria vaccine based on this antigen.
Antibody signatures of asymptomatic Plasmodium falciparum malaria infections measured from dried blood spots
Authors: Markwalter Christine F. , Nyunt Myat Htut , Han Zay Yar , Henao Ricardo , Jain Aarti , Taghavian Omid , Felgner Philip L. , Han Kay Thwe , Nyunt Myaing M. , Plowe Christopher V.
Published: September 2021

Background

Screening malaria-specific antibody responses on protein microarrays can help identify immune factors that mediate protection against malaria infection, disease, and transmission, as well as markers of past exposure to both malaria parasites and mosquito vectors. Most malaria protein microarray work has used serum as the sample matrix, requiring prompt laboratory processing and a continuous cold chain, thus limiting applications in remote locations. Dried blood spots (DBS) pose minimal biohazard, do not require immediate laboratory processing, and are stable at room temperature for transport, making them potentially superior alternatives to serum. The goals of this study were to assess the viability of DBS as a source for antibody profiling and to use DBS to identify serological signatures of low-density Plasmodium falciparum infections in malaria-endemic regions of Myanmar.

Methods

Matched DBS and serum samples from a cross-sectional study in Ingapu Township, Myanmar were probed on protein microarrays populated with P. falciparum antigen fragments. Signal and trends in both sample matrices were compared. A case-control study was then performed using banked DBS samples from malaria-endemic regions of Myanmar, and a regularized logistic regression model was used to identify antibody signatures of ultrasensitive PCR-positive P. falciparum infections.

Results

Approximately 30% of serum IgG activity was recovered from DBS. Despite this loss of antibody activity, antigen and population trends were well-matched between the two sample matrices. Responses to 18 protein fragments were associated with the odds of asymptomatic P. falciparum infection, albeit with modest diagnostic characteristics (sensitivity 58%, specificity 85%, negative predictive value 88%, and positive predictive value 52%).

Conclusions

Malaria-specific antibody responses can be reliably detected, quantified, and analysed from DBS, opening the door to serological studies in populations where serum collection, transport, and storage would otherwise be impossible. While test characteristics of antibody signatures were insufficient for individual diagnosis, serological testing may be useful for identifying exposure to asymptomatic, low-density malaria infections, particularly if sero-surveillance strategies target individuals with low previous exposure as sentinels for population exposure.
Formulating RALA/Au nanocomplexes to enhance nanoparticle internalisation efficiency, sensitising prostate tumour models to radiation treatment
Authors: Bennie Lindsey A. , Feng Jie , Emmerson Christopher , Hyland Wendy B. , Matchett Kyle B. , McCarthy Helen O. , Coulter Jonathan A.
Published: September 2021

Background

Gold nanoparticles (AuNP) are effective radiosensitisers, however, successful clinical translation has been impeded by short systemic circulation times and poor internalisation efficiency. This work examines the potential of RALA, a short amphipathic peptide, to enhance the uptake efficiency of negatively charged AuNPs in tumour cells, detailing the subsequent impact of AuNP internalisation on tumour cell radiation sensitivity.

Results

RALA/Au nanoparticles were formed by optimising the ratio of RALA to citrate capped AuNPs, with assembly occurring through electrostatic interactions. Physical nanoparticle characteristics were determined by UV–vis spectroscopy and dynamic light scattering. Nano-complexes successfully formed at w:w ratios > 20:1 (20 µg RALA:1 µg AuNP) yielding positively charged nanoparticles, sized < 110 nm with PDI values < 0.52. ICP-MS demonstrated that RALA enhanced AuNP internalisation by more than threefold in both PC-3 and DU145 prostate cancer cell models, without causing significant toxicity. Importantly, all RALA-AuNP formulations significantly increased prostate cancer cell radiosensitivity. This effect was greatest using the 25:1 RALA-AuNP formulation, producing a dose enhancement effect (DEF) of 1.54 in PC3 cells. Using clinical radiation energies (6 MV) RALA-AuNP also significantly augmented radiation sensitivity. Mechanistic studies support RALA-AuNP nuclear accumulation resulting in increased DNA damage yields.

Conclusions

This is the first study to demonstrate meaningful radiosensitisation using low microgram AuNP treatment concentrations. This effect was achieved using RALA, providing functional evidence to support our previous imaging study indicating RALA-AuNP nuclear accumulation.

Graphic abstract
Thermo-sensitive electroactive hydrogel combined with electrical stimulation for repair of spinal cord injury
Authors: Liu Wei , Luo Yiqian , Ning Cong , Zhang Wenjing , Zhang Qingzheng , Zou Haifeng , Fu Changfeng
Published: September 2021

The strategy of using a combination of scaffold-based physical and biochemical cues to repair spinal cord injury (SCI) has shown promising results. However, integrating conductivity and neurotrophins into a scaffold that recreates the electrophysiologic and nutritional microenvironment of the spinal cord (SC) remains challenging. In this study we investigated the therapeutic potential of a soft thermo-sensitive polymer electroactive hydrogel (TPEH) loaded with nerve growth factor (NGF) combined with functional electrical stimulation (ES) for the treatment of SCI. The developed hydrogel exhibits outstanding electrical conductance upon ES, with continuous release of NGF for at least 24 days. In cultured nerve cells, TPEH loaded with NGF promoted the neuronal differentiation of neural stem cells and axonal growth, an effect that was potentiated by ES. In a rat model of SCI, TPEH combined with NGF and ES stimulated endogenous neurogenesis and improved motor function. These results indicate that the TPEH scaffold that combines ES and biochemical cues can effectively promote SC tissue repair.
Collaboration on evidence synthesis in Africa: a network study of growing research capacity
Authors: Pan Jiayi , Zhong Yongqi , Young Sarah , Niezink Nynke M. D.
Published: September 2021

Background

Evidence-based practice in medicine and social policy relies heavily on evidence synthesis. To translate evidence into practical guidelines for low- and middle-income countries, local expertise is essential. The objectives of this study are to assess the change in capacity for conducting evidence synthesis in Africa and to identify key African institutions for regional capacity-building. We take on a network perspective, considering that the position of an institution in the African evidence ecosystem is one constituent of its research capacity.

Methods

We systematically identified 3548 evidence synthesis publications between 2008 and 2019 with at least one author in Africa from the Web of Science Core Collection. These articles involved 3769 institutions. Longitudinal institution-level collaboration network data were constructed based on co-authorship information. We used social network analysis to examine the institutions’ connectivity and tendency for intra- and interregional collaboration. We also identified the degree- and betweenness-central African institutions and explored the structure and composition of their local network neighbourhoods.

Results

The number of African institutions involved in evidence synthesis has increased substantially over the last decade, from 31 in 2008 to 521 in 2019, and so has the number of evidence synthesis publications with authors in Africa. African institutions in the evidence ecosystem have also become more connected during this period. Although the amount of intercontinental collaboration continues to exceed that of regional collaboration, the tendency for African institutions to collaborate with partners in Africa is increasing. We identified seven institutions—in South Africa, Egypt and Uganda—as central to the collaboration networks between 2008 and 2019, all of whom showed a tendency to collaborate across sectors.

Conclusion

The development of more regionally based network-building initiatives would help to foster communities of practice and inter-institutional collaboration, strengthening regional research capacity. Moreover, the analysis in this study adds depth beyond a simple bibliometric analysis and illustrates that network analysis could provide a useful tool to evaluate the effectiveness of capacity-building strategies and programmes in the future.
Cost-effectiveness analysis for SilAtro-5-90 adjuvant treatment in the management of recurrent tonsillitis, compared with usual care only
Authors: Ostermann Thomas , Park A-La , De Jaegere Sabine , Fetz Katharina , Klement Petra , Raak Christa , McDaid David
Published: September 2021

Purpose

Antibiotics are one possible treatment for patients with recurrent acute throat infections (ATI), but effectiveness can be modest. In view of worries over antibiotic resistance, treatment pathways that reduce recurrence of ATI are essential from a public health perspective. Integrative treatment strategies can be an option but there is still a high demand to provide evidence of their cost effectiveness.

Methods

We constructed a 4-state Markov model to compare the cost-effectiveness of SilAtro-5-90 as adjuvant homeopathic therapy to care as usual with care as usual alone in reducing the recurrence of ATI for children and adults with suspected moderate recurrent tonsillitis. The analysis was performed from a societal perspective in Germany over a 2-year period. Results are reported separately for children < 12 and for individuals aged 12 and over. The model draws on evidence from a multi-centre randomised clinical trial that found this strategy effective in reducing recurrence of ATI. Costs in 2019 € and outcomes after 1 year are discounted at a rate of 3% per annum.

Results

For adults and adolescents aged 12 years and over, incremental cost per ATI averted in the adjuvant therapy group was €156.64. If individuals enter the model on average with a history of 3.33 previous ATIs, adjuvant therapy has both lower costs and better outcomes than care as usual. For children (< 12 years) adjuvant therapy had both lower costs and ATI than care as usual. The economic case is stronger if adjuvant treatment reduces surgical referral. At a hypothetical cost per ATI averted threshold of €1000 probabilistic sensitivity analysis suggests Silatro-5-90 has a 65% (adults) and 71% (children) chance of being cost-effective.

Conclusion

Our results indicate the importance of considering homeopathy as adjuvant therapy in the treatment of ATIs in individuals with recurrent tonsillitis from a socio-economic perspective. Further evaluation should assess how differences in uptake and sustained use of homeopathic adjuvant therapy, as well as changing patterns of antibiotic prescribing, impact on cost effectiveness.
Walking cadence (steps/min) and intensity in 61–85-year-old adults: the CADENCE-Adults study
Authors: Tudor-Locke Catrine , Mora-Gonzalez Jose , Ducharme Scott W. , Aguiar Elroy J. , Schuna John M. , Barreira Tiago V. , Moore Christopher C. , Chase Colleen J. , Gould Zachary R. , Amalbert-Birriel Marcos A. , Chipkin Stuart R. , Staudenmayer John
Published: September 2021

Background

Heuristic (i.e., evidence-based, rounded) cadences of ≥100 and ≥ 130 steps/min have consistently corresponded with absolutely-defined moderate (3 metabolic equivalents [METs]) and vigorous (6 METs) physical activity intensity, respectively, in adults 21–60 years of age. There is no consensus regarding similar thresholds in older adults.

Purpose

To provide heuristic cadence thresholds for 3, 4, 5, and 6 METs in 61–85-year-old adults.

Methods

Ninety-eight community-dwelling ambulatory and ostensibly healthy older adults (age = 72.6 ± 6.9 years; 49% women) walked on a treadmill for a series of 5-min bouts (beginning at 0.5 mph with 0.5 mph increments) in this laboratory-based cross-sectional study until: 1) transitioning to running, 2) reaching ≥75% of their age-predicted maximum heart rate, or 3) reporting a Borg rating of perceived exertion > 13. Cadence was directly observed and hand-tallied. Intensity (oxygen uptake [VO2] mL/kg/min) was assessed with indirect calorimetry and converted to METs (1 MET = 3.5 mL/kg/min). Cadence thresholds were identified via segmented mixed effects model regression and using Receiver Operating Characteristic (ROC) curves. Final heuristic cadence thresholds represented an analytical compromise based on classification accuracy (sensitivity, specificity, positive and negative predictive value, and overall accuracy).

Results

Cadences of 103.1 (95% Prediction Interval: 70.0–114.2), 116.4 (105.3–127.4), 129.6 (118.6–140.7), and 142.9 steps/min (131.8–148.4) were identified for 3, 4, 5, and 6 METs, respectively, based on the segmented regression. Comparable values based on ROC analysis were 100.3 (95% Confidence Intervals: 95.7–103.1), 111.5 (106.1–112.9), 116.0 (112.4–120.2), and 128.6 steps/min (128.3–136.4). Heuristic cadence thresholds of 100, 110, and 120 were associated with 3, 4, and 5 METs. Data to inform a threshold for ≥6 METs was limited, as only 6/98 (6.0%) participants achieved this intensity.

Conclusions

Consistent with previous data collected from 21–40 and 41–60-year-old adults, heuristic cadence thresholds of 100, 110, and 120 steps/min were associated with 3, 4, and 5 METs, respectively, in 61–85-year-old adults. Most older adults tested did not achieve the intensity of ≥6 METs; therefore, our data do not support establishing thresholds corresponding with this intensity level.

Trial registration

Clinicaltrials.gov NCT02650258. Registered 24 December
2015.
Longitudinal analysis of symptom-based clustering in patients with primary Sjogren’s syndrome: a prospective cohort study with a 5-year follow-up period
Authors: Lee Jennifer Jooha , Park Young Jae , Park Misun , Yim Hyeon Woo , Park Sung Hwan , Kwok Seung-Ki
Published: September 2021

Background

Sjogren’s syndrome (SS) is a heterogenous disease with various phenotypes. We aimed to provide a relevant subclassification based on symptom-based clustering for patients with primary (p) SS.

Methods

Data from patients in a prospective pSS cohort in Korea were analysed. Latent class analysis (LCA) was performed using patient reported outcomes, including pain, fatigue, dryness, and anxiety/depression. Clinical and laboratory differences between the classes were analysed. Latent transition analysis (LTA) was applied to the longitudinal data (annually for up to 5 years) to assess temporal stability of the classifications.

Results

LCA identified three classes among 341 patients with pSS (i.e., ‘high symptom burden’, ‘dryness dominant’, ‘low symptom burden’). Each group had distinct laboratory and clinical phenotypes. LTA revealed that class membership remained stable over time. Baseline class predicted future salivary gland function and damage accrual represented by a Sjogren’s syndrome disease damage index.

Conclusion

Symptom-based clustering of heterogenous patients with primary Sjogren’s syndrome provided a relevant classification supported by temporal stability over time and distinct phenotypes between the classes. This clustering strategy may provide more homogenous groups of pSS patients for novel treatment development and predict future phenotypic evolvement.
A new Mfn-2 related synthetic peptide promotes vascular smooth muscle cell apoptosis via regulating the mitochondrial apoptotic pathway by inhibiting Akt signaling
Authors: Zhang Xinxin , Xu Xiangyu , Lu Li , Wan Xiaoning , Qin Yating , Ruan Weibin , Lv Chao , He Lin , Guo Xiaomei
Published: September 2021

Background

Restenosis after angioplasty is a major challenge for the treatment of coronary artery diseases. Facilitation of vascular smooth muscle cell (VSMC) apoptosis may be an attractive approach to decrease the incidence of restenosis. We synthesized a 16-amino acid mitofusin-2 (Mfn-2) gene related peptide (MRSP) based on the sequence of the p21ras signature motif, the smallest functional sequence of the Mfn-2 gene with proapoptotic properties in VSMC. We investigated whether MRSP enhanced apoptotic activities to inhibit VSMC accumulation and neointimal hyperplasia in rats with carotid balloon injury.

Methods

VSMCs were treated with different concentrations of MRSP, the PI3K agonist 740 Y-P and the inhibitor LY294002. Cell apoptosis and related pathway molecules were assessed. MRSP was also given to rats with carotid artery balloon injury. Neointimal hyperplasia and cell apoptotic pathways were detected.

Results

In vitro experiments revealed that MRSP treatment significantly increased VSMC apoptosis and induced increases in procaspase-9 cleavage, caspase-3 activation, cytochrome c release from mitochondria to the cytoplasm and the Bax/Bcl-2 ratio but not caspase-8 expression, indicating that the mitochondrial apoptotic cascade was activated by MRSP, which might be attributed to suppression of the PI3K/Akt signaling pathway. We further found that the PI3K agonist 740 Y-P prevented and that the inhibitor LY294002 strengthened the proapoptotic effects of MRSP. MRSP strongly inhibited neointimal hyperplasia and VSMC accumulation, but increased VSMC apoptosis in the vascular wall after balloon injury. Moreover, MRSP substantially enhanced Bax and cleaved caspase-3 expression and decreased Bcl-2 levels in intima, accompanied by decreased levels of phosphorylated Akt and PI3K in vivo.

Conclusions

Taken together, the present study showed that MRSP treatment results in a strong proapoptotic effect by activating the mitochondrial apoptotic cascade through suppression of the PI3K/Akt pathway.
An emerging and variant viral promoter of HIV-1 subtype C exhibits low-level gene expression noise
Authors: Ali Haider , Bhange Disha , Mehta Kavita , Gohil Yuvrajsinh , Prajapati Harshit Kumar , Byrareddy Siddappa N. , Buch Shilpa , Ranga Udaykumar
Published: September 2021

Background

We observe the emergence of several promoter-variant viral strains in India during recent years. The variant viral promoters contain additional copies of transcription factor binding sites present in the viral modulatory region or enhancer, including RBEIII, LEF-1, Ap-1 and/or NF-κB. These sites are crucial for governing viral gene expression and latency. Here, we infer that one variant viral promoter R2N3-LTR containing two copies of RBF-2 binding sites (an RBEIII site duplication) and three copies of NF-κB motifs may demonstrate low levels of gene expression noise as compared to the canonical RN3-LTR or a different variant R2N4-LTR (a duplication of an RBEIII site and an NF-κB motif). To demonstrate this, we constructed a panel of sub-genomic viral vectors of promoter-variant LTRs co-expressing two reporter proteins (mScarlet and Gaussia luciferase) under the dual-control of Tat and Rev. We established stable pools of CEM.NKR-CCR5 cells (CEM-CCR5RL reporter cells) and evaluated reporter gene expression under different conditions of cell activation.

Results

The R2N3-LTR established stringent latency that was highly resistant to reversal by potent cell activators such as TNF-α or PMA, or even to a cocktail of activators, compared to the canonical RN3- or the variant R2N4-LTR. The R2N3-LTR exhibited low-level basal gene expression in the absence of cell activation that enhanced marginally but significantly when activated. In the presence of Tat and Rev, trans-complemented in the form of an infectious virus, the R2N3-LTR demonstrated gene expression at levels comparable to the wild-type viral promoter. The R2N3-LTR is responsive to Tat and Rev factors derived from viral strains representing diverse genetic subtypes.

Conclusion

With extremely low-level transcriptional noise, the R2N3-LTR can serve as an excellent model to examine the establishment, maintenance, and reversal of HIV-1 latency. The R2N3-LTR would also be an ideal viral promoter to develop high-throughput screening assays to identify potent latency-reversing agents since the LTR is not affected by the usual background noise of the cell.
Multiple phenotypic traits as triggers of host attacks towards ant symbionts: body size, morphological gestalt, and chemical mimicry accuracy
Authors: von Beeren Christoph , Brückner Adrian , Hoenle Philipp O. , Ospina-Jara Bryan , Kronauer Daniel J. C. , Blüthgen Nico
Published: September 2021

Background

Ant colonies are plagued by a diversity of arthropod guests, which adopt various strategies to avoid or to withstand host attacks. Chemical mimicry of host recognition cues is, for example, a common integration strategy of ant guests. The morphological gestalt and body size of ant guests have long been argued to also affect host hostility, but quantitative studies testing these predictions are largely missing. We here evaluated three guest traits as triggers of host aggression—body size, morphological gestalt, and accuracy in chemical mimicry—in a community of six Eciton army ant species and 29 guest species. We quantified ant aggression towards 314 guests in behavioral assays and, for the same individuals, determined their body size and their accuracy in mimicking ant cuticular hydrocarbon (CHC) profiles. We classified guests into the following gestalts: protective, myrmecoid, staphylinid-like, phorid-like, and larval-shaped. We expected that (1) guests with lower CHC mimicry accuracy are more frequently attacked; (2) larger guests are more frequently attacked; (3) guests of different morphological gestalt receive differing host aggression levels.

Results

Army ant species had distinct CHC profiles and accuracy of mimicking these profiles was variable among guests, with many species showing high mimicry accuracy. Unexpectedly, we did not find a clear relationship between chemical host similarity and host aggression, suggesting that other symbiont traits need to be considered. We detected a relationship between the guests’ body size and the received host aggression, in that diminutive forms were rarely attacked. Our data also indicated that morphological gestalt might be a valuable predictor of host aggression. While most ant-guest encounters remained peaceful, host behavior still differed towards guests in that ant aggression was primarily directed towards those guests possessing a protective or a staphylinid-like gestalt.

Conclusion

We demonstrate that CHC mimicry accuracy does not necessarily predict host aggression towards ant symbionts. Exploitation mechanisms are diverse, and we conclude that, besides chemical mimicry, other factors such as the guests’ morphological gestalt and especially their body size might be important, yet underrated traits shaping the level of host hostility against social insect symbionts.
HoMEcare aRm rehabiLItatioN (MERLIN): preliminary evidence of long term effects of telerehabilitation using an unactuated training device on upper limb function after stroke
Authors: Rozevink Samantha G. , van der Sluis Corry K. , Hijmans Juha M.
Published: September 2021

Background

While short term effects on upper limb function of stroke patients after training with robotic devices have been studied extensively, long term effects are often not addressed. HoMEcare aRm rehabiLItatioN (MERLIN) is a combination of an unactuated training device using serious games and a telerehabilitation platform in the patient’s home situation. Short term effects showed that upper limb function improved after training with MERLIN. The aim was to determine long term effects on upper limb function and quality of life.

Methods

Six months after cessation of the 6 week MERLIN training program, the upper limb function and quality of life of 11 chronic stroke patients were assessed. Upper limb function was measured using the Wolf Motor Function Test (WMFT), Action Research Arm Test (ARAT) and Fugl-Meyer Assessment-Upper Extremity (FMA-UE). EuroQoL-5D (EQ-5D) was used to measure quality of life.

Results

The WMFT, ARAT and EQ-5D did not show significant differences 6 months after the training period compared to directly after training. At 6 months follow-up, FMA-UE results were significantly better than at baseline. Time plots showed a decreasing trend in all tests.

Conclusion

Training effects were still present at 6 months follow-up, since arm function seemed similar to directly after training and FMA-UE results were better than at baseline. However, because of the decreasing trend shown in all tests, it is questionable if improvements will be maintained longer than 6 months. Due to the sample size and study design, results should be interpreted with caution.

Trial registration This study is registered at the Netherlands Trial Register (NL7535). Registered 18-02-2019,https://www.trialregister.nl/trial/7535
Control, power, and responsibility: a qualitative study of local perspectives on problem drinking in Peruvian Andean highlands
Authors: Yamaguchi Sakiko , Lencucha Raphael , Brown Thomas G.
Published: September 2021

Background

Alcohol control has emerged as an important global health challenge due to the expanding influence of alcohol companies and limited control measures imposed by governments. In the Peruvian Andean highland, the ritual function of collective drinking is reported to have been weakened in response to the increased availability of alcohol and the experience of political violence. This study seeks to merge the broader political economy with local experience and culture to provide a deeper understanding of the dynamic between global processes and local realities.

Methods

We used purposive sampling to recruit participants. We conducted in-depth interviews (n = 28) and focus group discussions (n = 19) with community participants, teachers, health workers, alcohol vendors and police officers. Thematic analysis identified patterns of individual and collective meaning situated in relation to social, political and economic factors.

Results

Local perspectives and behaviour regarding loss of control over alcohol are shaped through the complex patterns of power and meaning exerted and experienced by different actors. Participants’ emphasis on parents’ lack of control over alcohol use by “abandoned” children reflects the structural vulnerability of some Andean families struggling with economic hardships. Participants also emphasized how alcohol consumption was tied to forms of control exerted by men in households. Participants expressed that some men demonstrated their masculine identity and symbolic power as the breadwinner through spending on alcohol. The third emphasis was tied to the market economy. Participants expressed that the expansion of the alcohol market and perceived absence of government control coupled with macroeconomic conditions, like poverty, shaped patterns of alcohol consumption.

Conclusion

Our findings illustrate how problem drinking is shaped not simply by an individual drinker’s lack of self-control but also by a regulatory environment that enables the unrestrained marketing of alcohol products and the creation of a culture of consumption. Harmful consumption is mediated by the reshaping of the Andean cultural practice of collective drinking. Attending to local perspectives is essential for policies and interventions that connect structural dynamics with the cultural and experiential aspects of alcohol consumption.