| 1. |
- Ababneh, Nidaa A., et al.
(author)
-
Identification of APTX disease-causing mutation in two unrelated Jordanian families with cerebellar ataxia and sensitivity to DNA damaging agents
- 2020
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:8
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Ataxia with oculomotor apraxia type 1 (AOA1) is a rare autosomal recessive cerebellar ataxia, caused by mutations in the APTX gene. The disease is characterized by early-onset cerebellar ataxia, oculomotor apraxia and severe axonal polyneuropathy. The aim of this study was to detect the disease-causing variants in two unrelated consanguineous Jordanian families with cerebellar ataxia using whole exome sequencing (WES), and to correlate the identified mutation(s) with the clinical and cellular phenotypes. METHODS: WES was performed in three affected individuals and segregation analysis of p.W279* APTX candidate variant was performed. Expression levels of APTX were measured in patients' skin fibroblasts and peripheral blood mononuclear cells, followed by western blot analysis in skin fibroblasts. Genotoxicity assay was performed to detect the sensitivity of APTX mutated cells to H2O2, MMC, MMS and etoposide. RESULTS: A recurrent homozygous nonsense variant in APTX gene (c.837G>A, p.W279*) was revealed in all affected individuals. qRT-PCR showed normal APTX levels in peripheral blood and lower levels in fibroblast cells. However, western blot showed the absence of APTX protein in patients' skin fibroblasts. Significant hypersensitivity to H2O2, MMC and etoposide and lack of sensitivity to MMS were noted. CONCLUSIONS: This is the first study to report the identification of a nonsense variant in the APTX gene (c.837G>A; p.W279*) in AOA1 patients within the Jordanian population. This study confirmed the need of WES to assist in the diagnosis of cerebellar ataxia and it emphasizes the importance of studying the pathophysiology of the APTX gene.
|
|
| 2. |
- Abe, Takafumi, et al.
(author)
-
Number of teeth and masticatory function are associated with sarcopenia and diabetes mellitus status among community-dwelling older adults : A Shimane CoHRE study
- 2021
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:6 June
-
Journal article (peer-reviewed)abstract
- Objectives: We aimed to examine the number of teeth and masticatory function as oral health indices and clarify their roles in the pathogenesis of sarcopenia and diabetes mellitus in communitydwelling older adults. Subjects and methods: This cross-sectional study was conducted with 635 older adults in Ohnan, Shimane Prefecture, in rural Japan. The number of teeth and masticatory function (measured by the number of gummy jelly pieces collected after chewing) were evaluated by dental hygienists. Sarcopenia status was assessed using handgrip strength, skeletal muscle index, calf circumference, and a possible sarcopenia diagnosis based on the Asian Working Group for Sarcopenia 2019. Diabetes mellitus status was defined as a hemoglobin A1c level ≥6.5% or self-reported diabetes. A multivariable logistic regression model was used to analyze the association between oral health, sarcopenia, and diabetes mellitus after adjusting for confounders. Results: After adjusting for all confounders, logistic regression analysis showed that the number of remaining teeth was negatively associated with a low level of handgrip strength (odds ratio [OR], 0.961; 95% confidence interval [CI], 0.932-0.992) and possible sarcopenia (OR, 0.949; 95% CI, 0.907-0.992). Higher levels of masticatory function were also negatively associated with a low level of handgrip strength (OR, 0.965; 95% CI, 0.941-0.990) and possible sarcopenia (OR, 0.941; 95% CI, 0.904-0.979). Logistic regression analysis showed that the number of remaining teeth and a higher level of masticatory function were negatively associated with diabetes mellitus (OR, 0.978; 95% CI, 0.957-0.999; OR, 0.976; 95% CI, 0.960-0.992, respectively). Conclusion: Our findings suggest that improvement in oral health, including the maintenance of masticatory function and remaining teeth, may contribute to the prevention of sarcopenia and diabetes mellitus in older adults.
|
|
| 3. |
- Abe, Takafumi, et al.
(author)
-
Social participation and physical prefrailty in older Japanese adults : The Shimane CoHRE study
- 2020
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:12 December
-
Journal article (peer-reviewed)abstract
- As older adults in an early stage (prefrailty) of frailty may return to a healthy state, it is necessary to examine the prevention of prefrailty. In this context, the number and types of social participation activities associated with physical prefrailty in community-dwelling older adults have remained relatively unexplored. This cross-sectional study investigates this issue by analyzing 616 participants living in Okinoshima, Shimane, a rural area of Japan, in 2019. Frailty was assessed using the 5-item frailty phenotype (unintentional weight loss, selfreported exhaustion, weakness, slow walking speed, and low physical activity). Data on social participation were obtained using a questionnaire based on participants' level of involvement with volunteer groups, sports clubs/groups, neighborhood associations, religious organizations/groups, and community elderly salons; their answers were categorized as "yes"if they answered "several times per year or more"and "no"if they answered "never."Binominal logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of prefrailty by the number or types of social participation activities, adjusted for gender, age, body mass index, smoking, medication-taking, educational attainment, working status, and living arrangement. Of the 616 participants, 273 (44.3%) and 28 (4.5%) had prefrailty and frailty, respectively. The analysis showed that the number of social participation activities was significantly associated with lower odds of prefrailty (OR = 0.83; 95% CI, 0.74-0.94). Regarding the types of social participation, sports clubs/groups were associated with lower odds of prefrailty (OR = 0.47; 95% CI, 0.31-0.73). Participation in neighborhood associations was associated with prefrailty/frailty (OR = 0.57; 95% CI, 0.37-0.86). These results suggest that increasing the number of social participation activities or involvement in sports clubs/groups and neighborhood associations may be important to prevent physical prefrailty in the older population.
|
|
| 4. |
- Aboshady, Hadeer Moursy, et al.
(author)
-
Genomic variants from RNA-seq for goats resistant or susceptible to gastrointestinal nematode infection
- 2021
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16
-
Journal article (peer-reviewed)abstract
- Gastrointestinal nematodes (GIN) are an important constraint in small ruminant production. Genetic selection for resistant animals is a potential sustainable control strategy. Advances in molecular genetics have led to the identification of several molecular genetic markers associated with genes affecting economic relevant traits. In this study, the variants in the genome of Creole goats resistant or susceptible to GIN were discovered from RNA-sequencing. We identified SNPs, insertions and deletions that distinguish the two genotypes, resistant and susceptible and we characterized these variants through functional analysis. The T cell receptor signalling pathway was one of the top significant pathways that distinguish the resistant from the susceptible genotype with 78% of the genes involved in this pathway showing genomic variants. These genomic variants are expected to provide useful resources especially for molecular breeding for GIN resistance in goats.
|
|
| 5. |
- Acciai, C, et al.
(author)
-
Institution and gender-related differences in publication speed before and during COVID-19
- 2022
-
In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:11, s. e0277011-
-
Journal article (peer-reviewed)abstract
- The COVID-19 pandemic elicited a substantial hike in journal submissions and a global push to get medical evidence quickly through the review process. Editorial decisions and peer-assessments were made under intensified time constraints, which may have amplified social disparities in the outcomes of peer-reviewing, especially for COVID-19 related research. This study quantifies the differential impact of the pandemic on the duration of the peer-review process for women and men and for scientists at different strata of the institutional-prestige hierarchy. Using mixed-effects regression models with observations clustered at the journal level, we analysed newly available data on the submission and acceptance dates of 78,085 medical research articles published in 2019 and 2020. We found that institution-related disparities in the average time from manuscript submission to acceptance increased marginally in 2020, although half of the observed change was driven by speedy reviews of COVID-19 research. For COVID-19 papers, we found more substantial institution-related disparities in review times in favour of authors from highly-ranked institutions. Descriptive survival plots also indicated that scientists with prestigious affiliations benefitted more from fast-track peer reviewing than did colleagues from less reputed institutions. This difference was more pronounced for journals with a single-blind review procedure compared to journals with a double-blind review procedure. Gender-related changes in the duration of the peer-review process were small and inconsistent, although we observed a minor difference in the average review time of COVID-19 papers first authored by women and men.
|
|
| 6. |
- Acuña Mora, Mariela, 1990, et al.
(author)
-
The longitudinal association between patient empowerment and patient-reported outcomes: What is the direction of effect?
- 2022
-
In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:11
-
Journal article (peer-reviewed)abstract
- Theoretical literature and cross-sectional studies suggest empowerment is associated with other patient-reported outcomes (PROs). However, it is not known if patient empowerment is leading to improvements in other PROs or vice versa.The present study aimed to examine the direction of effects between patient empowerment and PROs in young persons with congenital heart disease (CHD).As part of the STEPSTONES-CHD trial, adolescents with CHD from seven pediatric cardiology centers in Sweden were included in a longitudinal observational study (n = 132). Data were collected when patients were 16 (T0), 17 (T1) and 18 ½ years old (T2). The Gothenburg Young Persons Empowerment Scale (GYPES) was used to measure patient empowerment. Random intercepts cross-lagged panel models between patient empowerment and PROs (communication skills; patient-reported health; quality of life; and transition readiness) were undertaken.We found a significant cross-lagged effect of transition readiness over patient empowerment between T1 and T2, signifying that a higher level of transition readiness predicted a higher level of patient empowerment. No other significant cross-lagged relationships were found.Feeling confident before the transition to adult care is necessary before young persons with CHD can feel in control to manage their health and their lives. Clinicians interested in improving patient empowerment during the transitional period should consider targeting transition readiness.
|
|
| 7. |
- Adams, A. M., et al.
(author)
-
Growth dynamics among adolescent girls in Bangladesh : Evidence from nationally representative data spanning 2011-2014
- 2021
-
In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:7
-
Journal article (peer-reviewed)abstract
- BackgroundAdolescence is the last opportunity to reverse any growth faltering accumulated from fetal life through childhood and it is considered a crucial period to optimize human development. In Bangladesh, a growing double burden of underweight and obesity in adolescents is recognized, yet limited data exists on how, when, and where to intervene. This study assesses the dynamics of growth among adolescent girls in Bangladesh, providing insight about critical junctures where faltering occurs and where immediate interventions are warranted.MethodsWe pooled data from Bangladesh’s Food Security and Nutrition Surveillance Project collected between 2011 and 2014 to document the age dynamics of weight and linear growth. 20,572 adolescent girls were measured for height and 19,345 for weight. We constructed growth curves for height, weight, stunting, and underweight. We also stratified growth dynamics by wealth quintile to assess socioeconomic inequities in adolescent trajectories.ResultsHeight-for-age z-score (HAZ) in Bangladeshi girls deteriorates throughout adolescence and especially during the early years. Mean HAZ decreases by 0.20 standard deviations (sd) per year in early adolescence (10–14 years) vs 0.06 sd/year during late adolescence (15–19 years), while stunting increases by 16 percentage points (pp) vs 6.7 pp, respectively. Conversely, BMI-for-age z-score (BAZ) increases by 0.13 sd/year in early adolescence vs 0.02 sd/year in late adolescence, and underweight decreases by 12.8 pp vs 3.2 pp. Adolescent girls in all socioeconomic groups show a similar pattern of HAZ and BAZ dynamics, but the curve for the richest quintile stays above that of the poorest across all ages.ConclusionsTrends and levels of stunting and underweight among adolescent girls in Bangladesh are worrisome, suggesting substantial linear growth faltering in early adolescence, with improving weight-for-age occurring only as linear growth slows and stops. Given the rising burden of non-communicable diseases (NCDs) in Bangladesh and emerging evidence of the link between stunting and later chronic diseases, greater attention to adolescent growth and development is needed. Our findings suggest that, to address stunting, interventions in early adolescence would have the greatest benefits. School-based interventions could be a way to target this population.
|
|
| 8. |
- Afghahi, Henri, 1966, et al.
(author)
-
Long-term glycemic variability and the risk of mortality in diabetic patients receiving peritoneal dialysis.
- 2022
-
In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:1
-
Journal article (peer-reviewed)abstract
- The large amount of glucose in the dialysate used in peritoneal dialysis (PD) likely affects the glycemic control. The aim of this study was to investigate the association between HbA1c variability, as a measure of long-term glycemic variability, and the risk of all-cause mortality in diabetic patients with PD.325 patients with diabetes and ESRD were followed (2008-2018) in the Swedish Renal Registry. Patients were separated in seven groups according to level of HbA1c variability. The group with the lowest variability was denoted the reference. The ratio of the standard deviation (SD) to the mean of HbA1c, HbA1c (SD)/HbA1c (mean), i.e. the coefficient of variation (CV), was defined as HbA1c variability. Hazard ratios (HR) and 95% confidence intervals (CI) were examined using Cox regression analyses.During follow-up, 170 (52%) deaths occurred. The highest mortality was among patients with the second highest HbA1c variability, CV≥2.83 [n = 44 of which 68% patients died]. In the multivariate analyses where lowest HbA1c variability (CV≤0.51) was used as the reference group, HbA1c CV 2.83-4.60 (HR 3.15, 95% CI 1.78-5.55; p<0.001) and CV> 4.6 (HR 2.48, 95% CI 1.21-5.11; p = 0.014) were associated with increased risk of death.The high risk of all-cause mortality in patients with diabetes and PD increased significantly with elevated HbA1c variability, as measure of long-term glycemic control. This indicates that stable glycemia is associated with an improvement of survival; whereas more severe glycemic fluctuations, possibly caused by radical changes in dialysis regimes or peritonitis, are associated with a higher risk of mortality in diabetic patients with PD.
|
|
| 9. |
- Agback, Tatiana, et al.
(author)
-
H-1, C-13 and N-15 resonance assignment of the SARS-CoV-2 full-length nsp1 protein and its mutants reveals its unique secondary structure features in solution
- 2021
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16
-
Journal article (peer-reviewed)abstract
- Structural characterization of the SARS-CoV-2 full length nsp1 protein will be an essential tool for developing new target-directed antiviral drugs against SARS-CoV-2 and for further understanding of intra- and intermolecular interactions of this protein. As a first step in the NMR studies of the protein, we report the H-1, C-13 and N-15 resonance backbone assignment as well as the C beta of the apo form of the full-lengthSARS-CoV-2 nsp1 including the folded domain together with the flaking N- and C- terminal intrinsically disordered fragments. The 19.8 kD protein was characterized by high-resolution NMR. Validation of assignment have been done by using two different mutants, H81P and K129E/D48E as well as by amino acid specific experiments. According to the obtained assignment, the secondary structure of the folded domain in solution was almost identical to its previously published X-ray structure as well as another published secondary structure obtained by NMR, but some discrepancies have been detected. In the solution SARS-CoV-2 nsp1 exhibited disordered, flexible N- and C-termini with different dynamic characteristics. The short peptide in the beginning of the disordered C-terminal domain adopted two different conformations distinguishable on the NMR time scale. We propose that the disordered and folded nsp1 domains are not fully independent units but are rather involved in intramolecular interactions. Studies of the structure and dynamics of the SARS-CoV-2 mutant in solution are on-going and will provide important insights into the molecular mechanisms underlying these interactions.
|
|
| 10. |
- Agerskov, Simon, et al.
(author)
-
MRI diffusion and perfusion alterations in the mesencephalon and pons as markers of disease and symptom reversibility in idiopathic normal pressure hydrocephalus
- 2020
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:10
-
Journal article (peer-reviewed)abstract
- Introduction Core symptomatology in idiopathic normal pressure hydrocephalus (iNPH) points at dysfunction in the mesencephalon and pons indicating pathological changes in these regions, but only a few studies have addressed the issue. The aim of this study was to investigate diffusion (ADC) and perfusion patterns pre- and postoperatively in these areas in iNPH. Methods Twenty iNPH patients and 15 healthy controls were included. Patients underwent a clinical examination and brain MRI pre- and 3-6 months postoperatively. The MRI-scan included diffusion and dynamic susceptibility contrast perfusion weighted sequences. Regions of interest in the mesencephalon and pons were drawn on a FLAIR sequence and co-registered to ADC maps and perfusion data. Results There were no significant differences in pre or postoperative ADC compared to the control group, however postoperative ADC increased by 10% (p = 0.026) in the mesencephalon and 6% (p = 0.016) in the pons in all patients and also in the subgroup of shunt responders by 11% (p = 0.021) and 4% (p = 0.020), respectively. Preoperative relative cerebral blood flow (rCBF) was similar in iNPH patients and controls. Postoperatively, rCBF increased in shunt responders by 6% (p = 0.02) in the mesencephalon and 11% (p = 0.004) in the pons. This increase correlated with the degree of clinical improvement (r(s)= 0.80, p = 0.031 and r(s)= 0.66, p = 0.021, respectively). Conclusion The postoperative increase in ADC and the correlation between postoperative increase in rCBF and clinical improvement in the mesencephalon and pons shown in this study point at an involvement of these areas in the core pathophysiology and its reversibility in iNPH.
|
|
