bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic analysis reveals independent evolution of Plasmodium falciparum populations in Ethiopia
Authors: Abera Deriba , Kibet Caleb K. , Degefa Teshome , Amenga-Etego Lucas , Bargul Joel L. , Golassa Lemu
Published: March 2021

Background

Plasmodium falciparum parasite populations in Ethiopia have been experiencing local selective pressures from drugs and immunity, leading to evolutionary adaptation. However, there was a paucity of data on genomic characterization and evolutionary adaptations of P. falciparum isolates from the central area of Ethiopia.

Methods

Whole-genome analysis of 25 P. falciparum isolates from central Ethiopia, specifically from West Arsi, were studied to determine their genetic diversity, population structures, and signatures of selection in known drug resistance alleles against global isolates from Cambodia, Thailand, DR Congo, and Malawi.

Results

A total of 18,517 high-quality single-nucleotide polymorphisms (SNPs) were identified in Ethiopian P. falciparum isolates. About 84% of the Ethiopian P. falciparum isolates had a FWS value > 0.95 showing a dominant single genotype infection in most isolates at the time of collection with little potential for out-crossing as expected in areas with low transmission intensity. Within-host diversity of Ethiopian infections was significantly different from East African (p < 0.001), but not Southeast Asian infections (P > 0.05). A significant population structure has been observed by PCA and population differentiation between Ethiopian parasites and East African (Fst ~ 10%) and Southeast Asian populations (Fst ~ 18%), suggesting limited gene flow and the independent evolution of the Ethiopian parasite population. Moreover, a total of 125 genes under balancing selection was found that include ama1, trap, eba175, and lsa3, previously identified as targets of human host immunity. Recent directional selection analysis using integrated standardized haplotype score (IHS) did not detect any selection signatures in the Pfcrt, Pfdhfr, Pfdhps, Pfmdr1, and PfK13 genes. However, known drug resistance-conferring mutations analysis showed that at least one SNP marker was fixed in these genes, but not in Pfdhps and PfK13.

Conclusion

Plasmodium falciparum populations in the central region of Ethiopia was structurally diverged from both Southeast Asian and other East African populations. Malaria infections in Ethiopia had low within-host diversity, and parasites carry fixed chloroquine resistance markers despite the withdrawal of this drug for the treatment of P. falciparum.
Insecticide-treated net utilization and associated factors among pregnant women and under-five children in East Belessa District, Northwest Ethiopia: using the Health Belief model
Authors: Yirsaw Amlaku Nigusie , Gebremariam Resom Berhe , Getnet Wallelign Alemnew , Mihret Muhabaw Shumye
Published: March 2021

Background

Malaria during pregnancy and childhood is one of the major public health challenges globally. Its prevalence is huge in Africa, especially in sub-Saharan countries and Ethiopia. Insecticide-treated mosquito net (ITN) use is one of the primary malaria preventive strategies. Previous studies did not adequately address the health belief and behaviour-related correlates of ITN using health belief model (HBM), although a number of studies were conducted in this theme. Therefore, this study was aimed at assessing the prevalence and associated factors of ITN utilization among pregnant women and under five children in east Belessa district, northwest Ethiopia, 2020.

Methods

A community-based cross-sectional mixed study was conducted in east Belessa district from February 01–30/2020. A total of 724 eligible participants were included in the quantitative study. A multistage cluster sampling technique was used. The quantitative data were collected using an interviewer-administered structured questionnaire. Data were entered into Epi data version 4.6.0.2 and then exported to SPSS version 16 for analysis. The binary logistic regression model was fitted and the level of significance was declared based on AOR with its 95% CI and p-value ≤ 0.05. Meanwhile, the qualitative data were collected using focus group discussions and key informant interviews, and analysed using a thematic analysis approach.

Results

The prevalence of ITN utilization was 56.5% (95% CI 53.0, 60.2) and independently predicted by a corrugated iron roof of the house (AOR = 1.53; 95% CI 1.15, 2.22), rural residence (AOR = 1.59; 95% CI 1.11,2.28), ≥ 2 number of rooms in the house (AOR = 1.56; 95% CI 1.06, 2.30) and high level of perceived barrier (AOR = 0.53; 95% CI 0.38,0.74). In the qualitative findings, the main barrier was connected to misconceptions and misperception towards malaria and ITN.

Conclusion

The prevalence of ITN utilization in the study area was lower than the national target (100%). It was significantly associated with household characteristics, residence, and level of a perceived barrier. Reversing the community’s misconceptions through information, education and communication (IEC), and behavioural change communication (BCC) would enhance ITN utilization.
What is the yield of malaria reactive case detection in the Greater Mekong Sub-region? A review of published data and meta-analysis
Authors: Deen Jacqueline , Mukaka Mavuto , von Seidlein Lorenz
Published: March 2021

Background

Reactive malaria case detection involves the screening of those in contact with index cases and is used in countries in the Greater Mekong Sub-region. The yield of reactive case detection, defined here as the percentage of positive malaria cases among potential contacts who were screened, was assessed.

Methods

A literature search was conducted on PubMed to identify studies on reactive case detection in the Greater Mekong Sub-region. Eligible published articles were reviewed and pooled estimates from the studies were calculated, by type of malaria test used.

Results

Eighty-five publications were retrieved, of which 8 (9.4%) eligible articles were included in the analysis. The yield from reactive case detection ranged from 0.1 to 4.2%, with higher rates from PCR testing compared with microscopy and/or rapid diagnostic test. The overall yield from microscopy and/or rapid diagnostic test was 0.56% (95% CI 0.31–0.88%), while that from PCR was 2.35% (95% CI 1.19–3.87%). The two studies comparing different target groups showed higher yield from co-workers/co-travellers, compared with household contacts.

Conclusion

In low malaria transmission settings, the effectiveness of reactive case detection is diminishing. In the Greater Mekong Sub-region, modifying reactive case detection from household contacts to co-workers/co-travellers and from testing to presumptive treatment of targeted contacts, could increase the impact of this approach.
Association between heaviness of cigarette smoking and serious psychological distress is stronger in women than in men: a nationally representative cross-sectional survey in Japan
Authors: Tomioka Kimiko , Shima Midori , Saeki Keigo
Published: March 2021

Background

Higher smoking prevalence in people with serious psychological distress (SPD) is well-recognized. However, gender and age differences in the association between heaviness of cigarette smoking and SPD have not been fully investigated.

Methods

We used anonymized data from a nationally representative survey in Japan (33,925 men and 37,257 women). SPD was measured using the Kessler 6-item Psychological Distress Scale and defined as ≥ 13 points. Multiple logistic regression analyses stratified by gender and age-groups (20–44 years, 45–64 years, and ≥ 65 years) were used to estimate adjusted odds ratio (aOR) and 95% confidence interval (CI) for SPD.

Results

After adjusting for sociodemographic confounders including education, equivalent household expenditures, and employment contract, women had a significant association between heavier smoking and more frequent SPD: compared to never-smokers, aORs (95% CIs) of ex-smokers, current light smokers who smoked 1–10 cigarettes per day (CPD), current moderate smokers 11–20 CPD, and current heavy smokers ≥ 21 CPD were 1.22 (0.92–1.63), 1.52 (1.25–1.84), 1.75 (1.46–2.09), and 2.22 (1.59–3.10), respectively (P-trend < 0.001). A significant positive association among women was consistent across all age-groups. Among men, there was no association between heaviness of cigarette smoking and SPD in all age-groups, and only current heavy smokers aged 20–44 years had a significantly higher OR for SPD (aOR, 1.37 [95% CI, 1.02–1.85]) than never-smokers.

Conclusions

There was a positive association between heaviness of cigarette smoking and SPD only among women, but not among men. For female smokers experiencing mental disorders, there is a need not only to improve mental health services but also to improve smoking-cessation support.
Associations of resilience with quality of life levels in adults experiencing homelessness and mental illness: a longitudinal study
Authors: Mejia-Lancheros Cilia , Woodhall-Melnik Julia , Wang Ri , Hwang Stephen W. , Stergiopoulos Vicky , Durbin Anna
Published: March 2021

Background

Homelessness constitutes a traumatic period that adversely impacts health and quality of life outcomes. The potential mitigating effects of resilience on quality of life levels in people experiencing homelessness are underresearched. This study assesses the longitudinal associations between resilience and quality of life scores among adults experiencing homelessness and mental illness.

Methods

This study is a secondary analysis of longitudinal data collected over 6 years from participants (N = 575) of the At Home/Chez Soi study on Housing First, Toronto site. Repeatedly measured resilience scores are the primary exposure and repeatedly measured global quality of life scores and mental health-specific quality of life scores are the primary outcomes. Mixed effect models were used to assess the association between the exposures and the outcomes.

Results

The majority of the participants were men (69.2%) and were on average 40.4 (± 11.8) years old at baseline. The average resilience score ranged between 5.00 to 5.62 over 8 data collection points across the 6-year follow-up period. After adjusting for gender, age, ethno-racial background, Housing First intervention, physical and mental comorbidities, and lifetime homelessness, higher resilience scores were positively associated with higher Global quality of life (Adjusted-coefficient: 0.23, 95% CI 0.19–0.27) and mental health-related quality of life values (Adjusted-coefficient: 4.15, 95% CI 3.35–4.95).

Conclusion

In homeless adults with mental illness, higher resilience levels were positively associated with higher global and mental health related quality of life values. Further interventions and services aimed to enhance resilience mechanisms and strategies are warranted to enhance better mental health and quality of life outcomes of this population group.

Trial registration

At Home/Chez Soi trial was registered with ISRCTN, ISRCTN42520374. Registered 18 September 2009, http://www.isrctn.com/ISRCTN42520374.
Psychometric validation of the French self and proxy versions of the PedsQL™ 4.0 generic health-related quality of life questionnaire for 8–12 year-old children
Authors: Amedro Pascal , Huguet Helena , Macioce Valerie , Dorka Raphael , Auer Annie , Guillaumont Sophie , Auquier Pascal , Abassi Hamouda , Picot Marie-Christine
Published: March 2021

Background

The Pediatric Quality of Life Inventory Version 4.0 (PedsQLTM4.0) is a generic health-related quality of life (HRQoL) questionnaire, widely used in pediatric clinical trials but not yet validated in France. We performed the psychometric validation of the self and proxy PedsQLTM4.0 generic questionnaires for French children aged 8–12 years old.

Methods

This bicentric cross-sectional study included 123 children and their parents with congenital heart disease (CHD) and 97 controls. The psychometric validation method was based on the consensus-based standards for the selection of health measurement instruments (COSMIN). The reliability was tested using the intraclass correlation coefficient (ICC). To evaluate the validity of this scale, content, face, criterion, and construct validity psychometric proprieties were tested. Acceptability was studied regarding questionnaires’ completion and the existence of a floor or a ceiling effect.

Results

Test–retest reliability intra-class correlation coefficients were mainly in good range (0.49–0.66). Face validity was very good among parents (0.85) and children (0.75). Content validity was good (0.70), despite misinterpretation of some items. In construct validity, each subscale had acceptable internal consistency reliability (Cronbach's α > 0.72 in self-reports, > 0.69 in proxy-reports). In the confirmatory factor analysis, the goodness-of-fit statistics rejected the original structure with 4 factors. The exploratory factor analysis revealed an alternative two-factor structure corresponding to physical and psychological dimensions. Convergent validity was supported by moderate (> 0.41) to high correlations (0.57) between PedsQL and Kidscreeen questionnaires for physical, emotion and school dimensions. The ability of the PedsQL to discriminate CHD severity was better with physical, social and total scores for both self-reports and proxy-reports.

Conclusions

The PedsQLTM4.0 generic self and proxy HRQoL questionnaires found good psychometric properties, with regard to acceptability, responsiveness, validity, and reliability. This instrument appeared to be easy to use and comprehend within the target population of children aged 8 to 12 years old and their parents.

Trial registration: This study was approved by the South-Mediterranean-IV Ethics Committee and registered on ClinicalTrials.gov (NCT01202916), https://clinicaltrials.gov/ct2/show/NCT01202916.
Effect of macrophages in semen on sperm quality
Authors: Chen Gangxin , Zheng Beihong
Published: March 2021

Background

This was a cross-sectional study in China which analyzed the levels of macrophages (Mφ) in semen and evaluated the influence of Mφ levels in semen on sperm quality.

Methods

The subjects involves 78 males, 25- to 35-year old. The samples were divided into a low group (Mφ < 6 × 105/ml) and a high group (Mφ > 6 × 105/ml). Evaluation included consideration of the influencing factors of male semen quality, macrophage concentration, sperm motility, morphology, membrane integrity DNA fragmentation index (DFI), anti-sperm antibodies (AsAb), IL-10, and IL-12 in semen.

Results

There was no difference in the physical or chemical indices of the semen, sperm concentration, AsAb, IL-10, or IL-12 between the two groups (P > 0.05). The percentage of sperm forward motility (PR%), the rate of normal sperm shape, and the integrity of cell membranes in the low group were higher than those in the high group (P < 0.05), while the percentage of sperm inactivity (IM%), the rate of sperm head deformity, the rate of deformity in the neck and middle segment, the sperm deformity index (SDI), the teratozoospermia index (TZI), and the sperm DFI in the low group were lower than those in the high group (P < 0.05). The concentration of Mφ in the semen was linearly correlated with sperm concentration, sperm PR%, IM%, sperm normal shape rate, head deformity rate, neck and middle deformity rate, SDI, TZI, sperm DFI, and sperm cell membrane integrity (P < 0.05), but there was no linear correlation with IL-10 or IL-12 (P > 0.05).

Conclusions

The Mφ concentration in semen is not significantly correlated with semen volume or sperm concentration, but negatively correlated with sperm motility, morphology, cell membrane integrity, and DNA damage rate. There is no significant correlation between the macrophages and the concentration of IL-10 or IL-12.
A systematic review of evidence-based practice implementation in drug and alcohol settings: applying the consolidated framework for implementation research framework
Authors: Louie Eva , Barrett Emma L. , Baillie Andrew , Haber Paul , Morley Kirsten C.
Published: March 2021

Background

There is a paucity of translational research programmes to improve implementation of evidence-based care in drug and alcohol settings. This systematic review aimed to provide a synthesis and evaluation of the effectiveness of implementation programmes of treatment for patients with drug and alcohol problems using the Consolidated Framework for Implementation Research (CFIR).

Methods

A comprehensive systematic review was conducted using five online databases (from inception onwards). Eligible studies included clinical trials and observational studies evaluating strategies used to implement evidence-based psychosocial treatments for alcohol and substance use disorders. Extracted data were qualitatively synthesised for common themes according to the CFIR. Primary outcomes included the implementation, service system or clinical practice. Risk of bias of individual studies was appraised using appropriate tools. A protocol was registered with (PROSPERO) (CRD42019123812) and published previously (Louie et al. Systematic 9:2020).

Results

Of the 2965 references identified, twenty studies were included in this review. Implementation research has employed a wide range of strategies to train clinicians in a few key evidence-based approaches to treatment. Implementation strategies were informed by a range of theories, with only two studies using an implementation framework (Baer et al. J Substance Abuse Treatment 37:191-202, 2009) used Context-Tailored Training and Helseth et al. J Substance Abuse Treatment 95:26-34, 2018) used the CFIR). Thirty of the 36 subdomains of the CFIR were evaluated by included studies, but the majority were concerned with the Characteristics of Individuals domain (75%), with less than half measuring Intervention Characteristics (45%) and Inner Setting constructs (25%), and only one study measuring the Outer Setting and Process domains. The most common primary outcome was the effectiveness of implementation strategies on treatment fidelity. Although several studies found clinician characteristics influenced the implementation outcome (40%) and many obtained clinical outcomes (40%), only five studies measured service system outcomes and only four studies evaluated the implementation.

Conclusions

While research has begun to accumulate in domains such as Characteristics of Individuals and Intervention Characteristics (e.g. education, beliefs and attitudes and organisational openness to new techniques), this review has identified significant gaps in the remaining CFIR domains including organisational factors, external forces and factors related to the process of the implementation itself. Findings of the review highlight important areas for future research and the utility of applying comprehensive implementation frameworks.
Combining losartan with radiotherapy increases tumor control and inhibits lung metastases from a HER2/neu-positive orthotopic breast cancer model
Authors: Li Wende , Li Sen , Chen Ivy X. , Liu Yujiao , Ramjiawan Rakesh R. , Leung Chi-Ho , Gerweck Leo E. , Fukumura Dai , Loeffler Jay S. , Jain Rakesh K. , Duda Dan G. , Huang Peigen
Published: March 2021

Background

Patients with metastatic HER2/neu-positive (HER2/neu +) breast cancer (BC) often experience treatment resistance, disease recurrences and metastases. Thus, new approaches for improving the treatment of HER2/neu + BC to prevent metastatic dissemination are urgently needed. Our previous studies have shown that losartan, an angiotensin receptor blocker, increases tumor perfusion and decreases hypoxia in a number of tumor models. Hypoxia reduces the efficacy of radiation and increases metastases. We therefore hypothesized that by modifying tumor stroma and increasing oxygenation, losartan will improve the outcome of radiotherapy and inhibit disease progression in a highly metastatic HER2/neu + murine BC model.

Methods

We established a metastatic HER2/neu + murine BC line (MCa-M3C) and used it to generate mammary fat pad isografts in syngeneic female FVB/N mice. Starting on day 3 after orthotopic tumor implantation, we administered a 7-day losartan treatment (40 mg/kg BW, gavage daily); or a 7-day losartan treatment followed by 20 Gy single dose local irradiation (S-IR) on day 10 (tumor size ~ 100 mm3), or 20 Gy local fractionated (5 × 4 Gy daily) irradiation (F-IR) on days 10–14. We analyzed tumor-growth delay (TGD), development of spontaneous lung metastases, animal survival, tumor vascular density, and tumor hypoxia.

Results

Treatments with S-IR, F-IR, Losartan + S-IR, or Losartan + F-IR resulted in a significantly increased TGD (8–16 days) in MCa-M3C tumors versus controls. However, the combination of Losartan + S-IR and Losartan + F-IR further enhanced tumor response to radiation alone by increasing TGD an additional 5 to 8 days for both single and fractionated dose irradiation (P < 0.01), decreasing lung metastasis (Losartan + IR vs. Control, P < 0.025), and increasing animal survival (Losartan + IR vs. Control, P = 0.0303). In addition, losartan treatment significantly increased tumor vascularity (P = 0.0314) and decreased pimonidazole positive (hypoxic) area (P = 0.0002).

Conclusions

Combining losartan with local irradiation significantly enhanced tumor response, at least in part via reduced tumor hypoxia presumably due to increased tumor perfusion. Our findings suggest that combining losartan with radiotherapy is a potential new treatment strategy for local control and inhibiting metastasis in HER2 + BC.
Survivorship and prognostic factors for pleomorphic liposarcoma: a population-based study
Authors: Wan Lu , Tu Chao , Qi Lin , Li Zhihong
Published: March 2021

Background

Pleomorphic liposarcoma is the least common but most aggressive subtype of liposarcoma. Very few studies have presented data on pleomorphic liposarcoma specifically, often including a limited number of cases and short-term follow-up. As a result, the survivorship and prognostic characteristics of this tumor remain incompletely identified.

Study design and setting

Cross-sectional analysis of the Surveillance Epidemiology and End Results database (1996–2015).

Results

Overall survival for the entire series was 54% (95% confidence interval [CI], 49–58%) and 40% (95% CI, 35–45%) at 5 and 10 years, respectively. Disease-specific survival for the entire series was 60% (95% CI, 56–65%) and 53% (95% CI, 48–58%) at 5 and 10 years, respectively. Patients who survived 10 years or more were more likely to die of events unrelated to pleomorphic liposarcoma. Univariate and multivariate analysis demonstrated that not receiving cancer-directed surgery was an independent poor prognostic factor. Older age (≥ 65 years old) was associated with worse overall survival but not disease-specific survival. Tumor stage and radiotherapy showed different impact on survival depending on tumor size. In comparison to localized staged tumors, regional stage only predicts poor survival in patients with tumor size less than 5 cm, while distant stage is an independent worse prognosis factor. Radiotherapy only benefits patients with tumor size larger than 10 cm. These results were confirmed in competing risk analysis.

Conclusion

Survival rates of patients with pleomorphic liposarcoma has not changed over the past 20 years. Patients with distant stage have poor prognosis; regional stage indicates worse survival in patients with tumor size less than 5 cm. Receiving surgery could prolong the survival, while radiotherapy only benefits patients with large tumor size (> 10 cm). Older age is associated with poor overall survival but not disease-specific survival. Routine patient surveillance following initial diagnosis should at least be 10 years for pleomorphic liposarcoma.
Pluripotent stem cell-derived models of neurological diseases reveal early transcriptional heterogeneity
Authors: Sorek Matan , Oweis Walaa , Nissim-Rafinia Malka , Maman Moria , Simon Shahar , Hession Cynthia C. , Adiconis Xian , Simmons Sean K. , Sanjana Neville E. , Shi Xi , Lu Congyi , Pan Jen Q. , Xu Xiaohong , Pouladi Mahmoud A. , Ellerby Lisa M. , Zhang Feng , Levin Joshua Z. , Meshorer Eran
Published: March 2021

Background

Many neurodegenerative diseases develop only later in life, when cells in the nervous system lose their structure or function. In many forms of neurodegenerative diseases, this late-onset phenomenon remains largely unexplained.

Results

Analyzing single-cell RNA sequencing from Alzheimer’s disease (AD) and Huntington’s disease (HD) patients, we find increased transcriptional heterogeneity in disease-state neurons. We hypothesize that transcriptional heterogeneity precedes neurodegenerative disease pathologies. To test this idea experimentally, we use juvenile forms (72Q; 180Q) of HD iPSCs, differentiate them into committed neuronal progenitors, and obtain single-cell expression profiles. We show a global increase in gene expression variability in HD. Autophagy genes become more stable, while energy and actin-related genes become more variable in the mutant cells. Knocking down several differentially variable genes results in increased aggregate formation, a pathology associated with HD. We further validate the increased transcriptional heterogeneity in CHD8+/− cells, a model for autism spectrum disorder.

Conclusions

Overall, our results suggest that although neurodegenerative diseases develop over time, transcriptional regulation imbalance is present already at very early developmental stages. Therefore, an intervention aimed at this early phenotype may be of high diagnostic value.
Treating to target in psoriatic arthritis: assessing real-world outcomes and optimising therapeutic strategy for adults with psoriatic arthritis—study protocol for the MONITOR-PsA study, a trials within cohorts study design
Authors: Rombach Ines , Tillett William , Jadon Deepak , Tucker Laura , Watson Marion , Francis Anne , Sinomati Yvonne , Eldridge Lucy , Dritsaki Melina , Dutton Susan J. , Al-Mossawi Hussein , Gullick Nicola , Thompson Ben , Coates Laura C.
Published: March 2021

Background

The Tight Control of psoriatic arthritis (TICOPA) trial confirmed improved clinical outcomes with a treat to target (T2T) strategy in psoriatic arthritis (PsA). This consisted of 4-weekly review and escalation of ‘step up’ therapy (single disease modifying therapy (DMARD), combination DMARDs and then biologics) based on remission criteria. Based on this, a T2T approach is supported by European PsA treatment recommendations. However, it is not commonly implemented in routine care primarily due to feasibility and cost concerns. In the TICOPA trial, the same treatment regime was used for all participants regardless of their disease profile. Despite the recognition of PsA as a highly heterogeneous condition, no studies have tailored which drugs are used depending on disease severity. The cohort will establish real world outcomes for the T2T approach in PsA and also form the basis of a trials within cohorts (TWiCs) design to test alternative therapeutic approaches within embedded clinical trials providing an evidence base for treatment strategy in PsA.

Methods

The Multicentre Observational Initiative in Treat to target Outcomes in Psoriatic Arthritis (MONITOR-PsA) cohort will apply a T2T approach within routine care. It will recruit newly diagnosed adult patients with PsA starting systemic therapies. The cohort is observational allowing routine therapeutic care within NHS clinics but a T2T approach will be supported when monitoring treatment within the cohort. Eligible participants will be adults (≥18 years) with active PsA with ≥ 1 tender or swollen joints or enthesis who have not previously had treatment with DMARDs for articular disease.

Discussion

This study is the first TWiC designed to support a fully powered randomised drug trial. The results from the observational cohort will be compared with those observed in the TICOPA trial investigating the clinical effectiveness and health care costs of the pragmatic T2T approach. Nested trials will provide definitive RCT evidence establishing the optimal management of PsA within the T2T approach. The TWiCs design allows robust generalizability to routine healthcare, avoids disappointment bias, aids recruitment and in future will allow assessment of longer-term outcomes.

Trial registration

ClinicalTrials.govNCT03531073. Retrospectively registered on 21 May 2018.
The comparative effect of exposure to various risk factors on the risk of hyperuricaemia: diet has a weak causal effect
Authors: Topless Ruth K. G. , Major Tanya J. , Florez Jose C. , Hirschhorn Joel N. , Cadzow Murray , Dalbeth Nicola , Stamp Lisa K. , Wilcox Philip L. , Reynolds Richard J. , Cole Joanne B. , Merriman Tony R.
Published: March 2021

Background

Prevention of hyperuricaemia (HU) is critical to the prevention of gout. Understanding causal relationships and relative contributions of various risk factors to hyperuricemia is therefore important in the prevention of gout. Here, we use attributable fraction to compare the relative contribution of genetic, dietary, urate-lowering therapy (ULT) and other exposures to HU. We use Mendelian randomisation to test for the causality of diet in urate levels.

Methods

Four European-ancestry sample sets, three from the general population (n = 419,060) and one of people with gout (n = 6781) were derived from the Database of Genotypes and Phenotypes (ARIC, FHS, CARDIA, CHS) and UK Biobank. Dichotomised exposures to diet, genetic risk variants, BMI, alcohol, diuretic treatment, sex and age were used to calculate adjusted population and average attributable fractions (PAF/AAF) for HU (≥0.42 mmol/L [≥7 mg/dL]). Exposure to ULT was also assessed in the gout cohort. Two sample Mendelian randomisation was done in the UK Biobank using dietary pattern-associated genetic variants as exposure and serum urate levels as outcome.

Results

Adherence to dietary recommendations, BMI (< 25 kg/m2), and absence of the SLC2A9 rs12498742 urate-raising allele produced PAFs for HU of 20 to 24%, 59 to 69%, and 57 to 64%, respectively, in the three non-gout cohorts. In the gout cohort, diet, BMI, SLC2A9 rs12498742 and ULT PAFs for HU were 12%, 49%, 48%, and 63%, respectively. Mendelian randomisation demonstrated weak causal effects of four dietary habits on serum urate levels (e.g. preferentially drinking skim milk increased urate, β = 0.047 mmol/L, P = 3.78 × 10−8). These effects were mediated by BMI, and they were not significant (P ≥ 0.06) in multivariable models assessing the BMI-independent effect of diet on urate.

Conclusions

Diet has a relatively minor role in determining serum urate levels and HU. In gout, the use of ULT was the largest attributable fraction tested for HU.
Visit-to-visit variability of serum uric acid measurements and the risk of all-cause mortality in the general population
Authors: Tian Xue , Wang Anxin , Zuo Yingting , Chen Shuohua , Zhang Licheng , Wu Shouling , Luo Yanxia
Published: March 2021

Background

Evidence on longitudinal variability of serum uric acid (SUA) and risk of all-cause mortality in the general population is limited, as many prior studies focused on a single measurement of SUA.

Methods

A total of 53,956 participants in the Kailuan study who underwent three health examinations during 2006 to 2010 were enrolled. Variability of SUA was measured using the coefficient of variation (primary index), standard deviation, average real variability, and variability independent of the mean. Cox proportional hazard regressions were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the association of variability of SUA with subsequent risk of all-cause mortality, considering its magnitude and the direction and across different baseline SUA categories.

Results

Over a median follow-up of 7.04 years, 2728 participants died. The highest variability of SUA was associated with an increased risk of all-cause mortality, the HR was 1.33 (95% CI, 1.20–1.49) compared with the lowest variability. In this group, both a large fall (HR, 1.28; 95% CI, 1.14–1.44) and rise (HR, 1.18; 95% 1.05–1.32) in SUA were related to risk of all-cause mortality. These associations were similar across different baseline SUA categories. Consistent results were observed in alternative measures of SUA variability. Moreover, individuals with higher variability in SUA were more related to common risk factors than those with stable SUA.

Conclusions

Higher variability in SUA was independently associated with the risk of all-cause mortality irrespective of baseline SUA and direction of variability in the general population.
The effects of WeChat-based educational intervention in patients with ankylosing spondylitis: a randomized controlled trial
Authors: Song Yuqing , Xie Xia , Chen Yanling , Wang Ying , Yang Hui , Nie Anliu , Chen Hong
Published: March 2021

Background

Ankylosing spondylitis (AS), as a common inflammatory rheumatic disease, often causes depression and impaired health-related quality of life (QoL). Although positive effects of patient education have been demonstrated, limited studies explored the benefits of education via mobile applications for AS patients. This study aimed to evaluate the effects of the WeChat-based educational intervention on depression, health-related QoL, and other clinical outcomes in AS patients.

Methods

We conducted a single-blind randomized controlled trial from March to December 2017. Patients were recruited and randomized into the intervention group which received a 12-week WeChat-based educational intervention (consisting of four individual online educational sessions, online educational materials) or the control group receiving standard care. Data was collected at baseline and 12 weeks. Outcomes were measured by Beck Depression Inventory-II, the Medical Outcomes Study Short Form 36-item Health Survey (SF-36), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Patient Global Score (BAS-G), and visual analog scales.

Results

A total of 118 patients with AS were included and analyzed. Measures at baseline were comparable between groups. After the intervention, the intervention group reported significant higher scores of all domains of SF-36 except for physical functioning and validity, compared with the control group. Additionally, patients in the intervention group had lower depressive symptoms than the control group. No significant difference in other outcomes was observed at 12 weeks.

Conclusions

This study found that the 12-week educational intervention via WeChat had positive effects on reducing depressive symptoms and improving health-related QoL in Chinese patients with AS. We suggest that this intervention can be integrated into current routine care of AS patients.

Trial registration

This study has been approved by the hospital’s ethics committee (ID: 20160364) in 2016 and registered at the Chinese Clinical Trial Registry (registry number: ChiCTR-IPR-16009293).
Effects of combining diaphragm training with electrical stimulation on pain, function, and balance in athletes with chronic low back pain: a randomized clinical trial
Authors: Otadi Khadijeh , Nakhostin Ansari Noureddin , Sharify Shahriar , Fakhari Zahra , Sarafraz Hadi , Aria Amir , Rasouli Omid
Published: March 2021

Background

It is unknown how diaphragm training combined with electrical stimulation affects pain, function, static stability, and balance in athletes with chronic low back pain (CLBP). This study aimed to explore the effects of combining diaphragm training with electrical stimulation on pain, function, static stability, and dynamic balance in athletes with nonspecific CLBP.

Methods

The design was a randomized clinical trial. A total of 24 amateur athletes (12 women, 12 men, mean age: 35.2 ± 9.8) with nonspecific CLBP were randomly allocated into two groups. The experimental group (n = 12) received diaphragm training plus Transcutaneous Electrical Nerve Stimulation (TENS), while the control group (n = 12) received TENS alone. Both groups underwent 12 sessions over a four-week period. Static stability, dynamic balance, pain, and function were measured pre- and post-intervention.

Results

Analysis of variance 2 × 2 revealed greater improvements in pain (p < 0.001), static stability (p < 0.001), and dynamic balance (p < 0.01) in the experimental group compared to the control group. Function was improved in both groups following the interventions (p < 0.001), and there was a trend of a larger improvement in the experimental group than the control group (p = 0.09). Fisher’s exact test showed that the experimental group reported ≥50% improvement only in the pain score, not function, compared to the group that received TENS alone (p = 0.005).

Conclusions

Pain, function, static stability, and dynamic balance were improved in both groups following 12 intervention sessions. However, pain, static stability, and dynamic balance were improved to a greater extent in diaphragm training plus TENS than TENS alone in amateur athletes with CLBP. Therefore, it seems beneficial to add diaphragm training to the rehabilitation program for athletes with nonspecific CLBP.

Trial registration

The trial was retrospectively registered in the Iranian Registry of Clinical Trials (www.irct.ir) on September 10, 2020 as IRCT20090228001719N8.
Lifestyle weight-loss intervention may attenuate methylation aging: the CENTRAL MRI randomized controlled trial
Authors: Yaskolka Meir Anat , Keller Maria , Bernhart Stephan H. , Rinott Ehud , Tsaban Gal , Zelicha Hila , Kaplan Alon , Schwarzfuchs Dan , Shelef Ilan , Gepner Yftach , Li Jun , Lin Yifei , Blüher Matthias , Ceglarek Uta , Stumvoll Michael , Stadler Peter F. , Stampfer Meir J. , Kovacs Peter , Liang Liming , Shai Iris
Published: March 2021

Background

DNA methylation age (mAge), a methylation biomarker for the aging process, might serve as a more accurate predictor of morbidity and aging status than chronological age. We evaluated the role of multiple factors, including fat deposition, cardiometabolic risk factors and lifestyle weight-loss intervention, on the deviation of mAge from chronological age (mAge deviation) or 18-month change in mAge (∆mAge). In this sub-study of the CENTRAL magnetic resonance imaging weight-loss trial, we evaluated mAge by a validated 240-CpG-based prediction formula at baseline and after 18-month intervention of either low fat (LF) or mediterranean/low carbohydrate (MED/LC) diets.

Results

Among 120 CENTRAL participants with abdominal obesity or dyslipidemia, mAge (mean ± SD: 60.3 ± 7.5 years) was higher than the chronological age (48.6 ± 9.3 years) but strongly correlated (r = 0.93;p = 3.1 × 10–53). Participants in the lowest tertile of mAge deviation from their chronological age had significantly lower waist-circumference, visceral adipose tissue, intrahepatic fat (IHF) content, fasting-glucose and HOMA-IR, as compared with participants in the highest sex-specific residual tertile (p < 0.05 for all). IHF% remained associated with greater mAge deviation after further adjustments (β = 0.23;p = 0.02). After 18-month weight-loss lifestyle intervention, mAge remained significantly correlated with chronological age (r = 0.94,p = 1.5 × 10–55). mAging occurred, with no difference between lifestyle intervention groups (∆ = 0.9 ± 1.9 years in MED/LC vs. ∆ = 1.3 ± 1.9 years in LF;p = 0.2); however, we observed a mAging attenuation in successful weight losers (> 5% weight loss) vs. weight-loss failures ( ∆ = 0.6 years vs. ∆ = 1.1 years;p = 0.04), and in participants who completed the trial with healthy liver fat content (< 5% IHF) vs. participants with fatty liver (∆ = 0.6 years vs. ∆ = 1.8 years;p = 0.003). Overall, 18 months of weight-loss lifestyle intervention attenuated the mAging of the men, mainly the older, by 7.1 months than the expected (p < 0.05).

Conclusions

Lifestyle weight-loss intervention may attenuate mAging. Deviation of mAge from chronological age might be related to body fat distribution and glycemic control and could indicate biological age, health status and the risk for premature cardiometabolic diseases.

Trial registration: ClinicalTrials.gov NCT01530724. Registered 10 February 2012,https://clinicaltrials.gov/ct2/show/study/NCT01530724.
Existence results for infinite systems of the Hilfer fractional boundary value problems in Banach sequence spaces
Authors: Gholami Yousef
Published: March 2021

The main aim of this paper is to present some existence criteria for an infinite system of Hilfer fractional boundary value problems of the form$$ \mathcal{D}_{a^{+}}^{\alpha,\beta }u_{i}=-F_{i}(t,u),\quad u_{i}(a)=u_{i}(b)=0, a< t< b,i=1,2,\ldots, $$Da+α,βui=−Fi(t,u),ui(a)=ui(b)=0,a<t<b,i=1,2,…,in Banach sequence spaces of$c_{0}$c0and$l_{p},p\geq 1$lp,p≥1types. Our approach is based on the Darbo-type fixed point theorems acting on the condensing operators. The obtained existence results in each of the above sequence spaces are illustrated by presenting some numerical examples.
Sharing and connecting with others – patient experiences of radically open dialectical behavior therapy for anorexia nervosa and overcontrol: a qualitative study
Authors: Isaksson Martina , Ghaderi Ata , Wolf-Arehult Martina , Öster Caisa , Ramklint Mia
Published: March 2021

Background

Recovery rates after psychological treatments for anorexia nervosa are low to moderate, and in adults, no treatment outperforms any other. The aim of this study was to evaluate patient experiences of Radically open dialectical behavior therapy (RO DBT), a treatment developed for disorders related to maladaptive overcontrol.

Methods

Eleven female patients with anorexia nervosa were interviewed after either treatment completion (eight patients) or drop-out (three patients) from RO DBT. Interviews were transcribed and analyzed with inductive thematic analysis.

Results

The analysis yielded five main themes: 1) a comprehensive treatment, 2) the benefits of sharing and connecting with others, 3) growing trust, 4) moving toward valued goals – but some remain, and 5) doing well in treatment.

Conclusion

Patients appreciated what they described as a comprehensive treatment and holistic view of their problems, which helped them reduce both maladaptive overcontrol and eating disorder symptoms. Gradually sharing personal experiences both in- and outside therapy was described as essential and led to enhanced social connectedness.

Trial registration

The intervention study (Isaksson M, et al. J Behav Ther Exp Psychiatry. 71, 2021) that preceded this interview study was performed by the first, second, third, and fifth author, preregistered in the ISRCTN registry (no:ISRCTN47156042).
Geographical accessibility of medicines: a systematic literature review of pharmacy mapping
Authors: Tharumia Jagadeesan Cindrel , Wirtz Veronika J.
Published: March 2021

Background

Measuring access to medicines has often been limited to assessing availability and affordability, while little is known regarding other dimensions of access including geographical accessibility. Our study aims to provide a systematic review of literature on the accessibility of medicines by studying the geographical distribution of pharmacies using Spatial Analytical methods.

Methods

As systematic review of scientific peer-reviewed literature between 2000 and 2018 was carried out using PubMed, Web of Science, Google Scholar, Google and the Preferred Reporting items for Systematic Reviews and Meta-Analyses (PRISMA). Data regarding pharmacy density, distance to pharmacies in relation of pharmacy to sociodemographic factors and pharmacy characteristics were extracted from studies that meet the inclusion criteria.

Findings

Twenty papers fulfilled our inclusion criteria, of which only three were from middle income countries and rest from high-income economies. Pharmacy density per population was reported in 15 studies. Although geographical information was utilized in all studies, only 14 studies reported distance to pharmacies represented as Euclidean (straight line) distance. Disparities in accessibility was reported according to population income and rural or urban location. Seven studies described additional pharmacy characteristics including opening hours, presence of a pharmacist and delivery services.

Conclusions

Geographical accessibility is a key dimension of access to medicines. Pharmacy density per population is a relevant indicator to assess geographical accessibility which should be complemented by an equity analysis using socio-demographic information and population perception of accessibility.
Conversion surgery for metastatic gastric cancer at 2 years after initial diagnosis of cancer of unknown primary with metastasis of cervical lymph nodes and ovary: a case report
Authors: Suzuki Masaki , Hosaka Hisashi , Fukai Yasuyuki , Mochida Yasushi , Ozawa Daigo , Kogure Norimichi , Yamada Kazunosuke , Ojima Hitoshi
Published: March 2021

Background

Patients with stage IV gastric cancer have a poor prognosis despite improvements in intensive treatment regimens, including chemotherapy. Recently, conversion surgery has received much attention as it can provide long-term survival in stage IV gastric cancer patients who are responsive to chemotherapy. Herein, we describe the case of a patient who underwent conversion surgery for metastatic gastric cancer that was performed over 2 years after an initial diagnosis of cancer of unknown primary (CUP) with metastasis of the cervical lymph nodes and the ovary.

Case presentation

A 67-year-old woman with cervical lymphadenopathy was referred to our hospital. Computed tomography showed left cervical lymphadenopathy and bilateral ovarian enlargement. Endoscopic survey revealed no signs of malignancy in the upper or the lower gastrointestinal tract. Pathological findings after cervical lymphadenectomy revealed a signet-ring cell carcinoma and were suggestive of gastric cancer metastases. However, multiple evaluations yielded no evidence of gastric cancer and the patient was diagnosed with CUP. She was prescribed chemotherapy for gastric cancer and underwent bilateral oophorectomy after undergoing chemotherapy for 18 months. Pathologic analysis of oophorectomy tissue revealed findings identical to those seen in the cervical lymph nodes. At about 2 years after the initial diagnosis, an esophagogastroduodenoscopy revealed evidence of gastric cancer. We performed a distal gastrectomy with D2 lymphadenectomy. Her postoperative course was uneventful and she remains alive with no signs of disease recurrence at 3 months post-surgery.

Conclusions

To the best of our knowledge, this is the first report describing successful conversion surgery for stage IV gastric cancer in a patient whose cancer was definitively diagnosed 2 years after an initial diagnosis of CUP.
External limiting membrane: retinal structural barrier in diabetic macular edema
Authors: Saxena Sandeep , Akduman Levent , Meyer Carsten H.
Published: March 2021

Advances in spectral-domain optical coherence tomography (SD-OCT) technology have enhanced the understanding of external limiting membrane (ELM) and ellipsoid zone (EZ) in diabetic macular edema. An increase in VEGF has been demonstrated to be associated with sequential ELM and EZ disruption on SD-OCT. An intact ELM is a prerequisite for an intact EZ in DME. Anti-VEGF therapy leads to restoration of barrier effect of ELM. The ELM restores first followed by EZ restoration.