Category: Nevin Manimala

Brain. 2023 Apr 24:awad139. doi: 10.1093/brain/awad139. Online ahead of print.

ABSTRACT

Some carriers of human T-cell leukemia virus type 1 (HTLV-1), a retrovirus that primarily infects CD4+ T cells and causes lifelong infection, develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Current treatments for HAM/TSP are insufficient with problematic long-term side effects. This study evaluated the long-term safety and efficacy of the anti-CCR4 antibody mogamulizumab in patients with HAM/TSP over a 4-year period. We conducted an open-label, extended long-term study (UMIN trial number: UMIN000019942) of a Phase 1-2a trial with mogamulizumab for HAM/TSP (UMIN000012655). The study participants were patients with corticosteroid-resistant HAM/TSP who could walk 10 m with or without assistive tools. Mogamulizumab was administered at 0.01, 0.03, 0.1, or 0.3 mg/kg at intervals of ≥8 weeks (0.01 and 0.03 mg/kg) or ≥12 weeks (0.1 and 0.3 mg/kg). HTLV-1 proviral load, cerebrospinal fluid inflammatory markers, and clinical symptoms were summarized by descriptive statistics. Missing observations were imputed using the last-observation-carried-forward method. As a post-hoc analysis, we evaluated the therapeutic effect of mogamulizumab on gait function by comparing it with contemporary control data from a HAM/TSP patient registry. Of the 21 participants in the Phase 1-2a, 18 (86%) enrolled in the long-term study and 15 (71%) continued repeated doses of mogamulizumab for 4 years. The median dose was 0.1 mg/kg after 4 years. Seventeen of 21 participants (81%) experienced grade 1-2 skin-related adverse events. Observed grade 3 drug-related adverse effects included three cases of lymphopenia and one case each of microscopic polyangiitis, elevated levels of aspartate aminotransferase, and neutropenia. Four of 21 participants (19%) developed neutralizing antibodies. After 4 years, the peripheral blood proviral load and the number of infected cells in CSF decreased by 60.7% and 66.3%, respectively. Neopterin and CXCL10 CSF concentrations decreased by 37.0% and 31.0%, respectively. Among the 18 participants, spasticity and Osame Motor Disability Score (OMDS) improved in 17 (94%) and 4 (22%), respectively. However, 10 m walking time worsened by 7.3% on average. Comparison with the contemporary control group demonstrated that mogamulizumab inhibited OMDS progression (p = 0.02). The results of the study suggest that mogamulizumab has long-term safety and inhibitory effect on lower limb motor disability progression in corticosteroid-treated patients with HAM/TSP. This will provide a basis for the application of mogamulizumab in HAM/TSP treatment.

PMID:37093965 | DOI:10.1093/brain/awad139

Genome Biol Evol. 2023 Apr 24:evad067. doi: 10.1093/gbe/evad067. Online ahead of print.

ABSTRACT

The pangenome is the set of all genes present in a prokaryotic population. Most pangenomes contain many accessory genes of low and intermediate frequencies. Different population genetics processes contribute to the shape of these pangenomes, namely selection and fitness-independent-processes such as gene transfer, gene loss, and migration. However, their relative importance is unknown and highly debated. Here we argue that the debate around prokaryotic pangenomes arose due to the imprecise application of population genetics models. Most importantly, two different processes of horizontal gene transfer act on prokaryotic populations, which are frequently confused, despite their fundamentally different behavior. Genes acquired from distantly related organisms (termed here acquiring gene transfer, AGT) is most comparable to mutation in nucleotide sequences. In contrast, gene gain within the population (termed here spreading gene transfer, SGT) has an effect on gene frequencies that is identical to the effect of positive selection on single genes. We thus show that selection and fitness-independent population genetic processes affecting pangenomes are indistinguishable at the level of single gene dynamics. Nevertheless, population genetics processes are fundamentally different when considering the joint distribution of all accessory genes across individuals of a population. We propose that, to understand to which degree the different processes shaped pangenome diversity, the development of comprehensive models and simulation tools is mandatory. Furthermore, we need to identify summary statistics and measurable features that can distinguish between the processes, where considering the joint distribution of accessory genes across individuals of a population will be particularly relevant.

PMID:37093956 | DOI:10.1093/gbe/evad067

Med Sci Sports Exerc. 2023 Apr 24. doi: 10.1249/MSS.0000000000003196. Online ahead of print.

ABSTRACT

INTRODUCTION: Physical activity levels have decreased over past decades with most adolescents neither meeting the current physical activity recommendations nor demonstrating adequate cardiorespiratory fitness. Motor competence (MC) is foundational for a physically active lifestyle; however, children demonstrate significant differences in their levels of MC in a broad foundation of movement skills. This study investigated developmental patterns of physical activity and cardiorespiratory fitness in children across 4 years based on their longitudinal MC profiles.

METHODS: The data included annual measurements of MC, accelerometry-measured moderate-to-vigorous physical activity (MVPA), and cardiorespiratory fitness over 4 years from the age 11 to 15 (n = 1147, girls 582, boys 565). Latent profile analysis was used to identify longitudinal MC profiles and latent growth curve modeling to examine intercepts and slopes (s) of MVPA and cardiorespiratory fitness in these MC profiles.

RESULTS: Three different longitudinal MC profiles were identified: low, moderate, and high. The MC profiles showed significant differences in intercepts of cardiorespiratory fitness and MVPA. The high MC profile showed the highest intercepts for both, but also a statistically significant decline in MVPA over time (s = -3.36, p < .001). Cardiorespiratory fitness increased similarly in all three profiles over time: low (s = 1.20, p < .01), moderate (s = 1.28, p < .001), high (s = 2.21, p < .001).

CONCLUSIONS: These results highlight the long-term associations between different MC profiles and development of MVPA and cardiorespiratory fitness. Adolescents with lower MC demonstrated lower levels of MVPA and cardiorespiratory fitness, indicating decreased participation in physical activities that can optimally enhance cardiorespiratory fitness. However, significant differences in MVPA levels between MC profiles faded over time in adolescence, whereas significant differences in cardiorespiratory fitness remained.

PMID:37093949 | DOI:10.1249/MSS.0000000000003196

J Speech Lang Hear Res. 2023 Apr 24:1-24. doi: 10.1044/2023_JSLHR-22-00545. Online ahead of print.

ABSTRACT

PURPOSE: The clinical use of event-related potentials in patients with language disorders is increasingly acknowledged. For this purpose, normative data should be available. Within this context, healthy aging and gender effects on the electrophysiological correlates of semantic sentence comprehension were investigated.

METHOD: One hundred and ten healthy subjects (55 men and 55 women), divided among three age groups (young, middle aged, and elderly), performed a semantic sentence congruity task in the visual modality during electroencephalographic recording.

RESULTS: The early visual complex was affected by increasing age as shown by smaller P2 amplitudes in the elderly compared to the young. Moreover, the N400 effect in the elderly was smaller than in the young and was delayed compared to latency measures in both middle-aged and young subjects. The topography of age-related amplitude changes of the N400 effect appeared to be gender specific. The late positive complex effect was increased at frontal electrode sites from middle age on, but this was not statistically significant. No gender effects were detected regarding the early P1, N1, and P2, or the late positive complex effect.

CONCLUSION: Especially aging effects were found during semantic sentence comprehension, and this from the level of perceptual processing on. Normative data are now available for clinical use.

PMID:37093923 | DOI:10.1044/2023_JSLHR-22-00545

Int J Dent Hyg. 2023 Apr 24. doi: 10.1111/idh.12678. Online ahead of print.

ABSTRACT

OBJECTIVES: Translating the Oral Health Assessment Tool (OHAT) into Dutch and assessing the inter-rater reliability among community nurses.

METHODS: The original version of the OHAT was translated following the five stages of the ‘Guidelines for the Process of Cross-Cultural Adaptation’. After a forward and backward translation, consensus on the pre-final version was obtained in an expert panel discussion. This version was pre-tested on its comprehensibility among 31 nurses and hereafter finalized. Then, inter-rater reliability of the OHAT-NL was determined by two trained nurses during oral assessments of 37 care-dependent community-dwelling older people. Intraclass correlation coefficient (ICC) and the Cohen’s kappa statistic for individual items were estimated.

RESULTS: Feedback from nurses in the pre-test did lead to minor changes of the OHAT-NL. Inter-rater reliability was good (ICC 0.79; 95% CI 0.63-0.89) on the total score. Agreement on item level ranged from fair to very good, the kappa ranged from 0.36-0.89.

CONCLUSIONS: OHAT is now available in Dutch having good inter-rater reliability among trained community nurses. Future research can further validate the OHAT-NL and develop intervention according to total OHAT-NL scores.

PMID:37093920 | DOI:10.1111/idh.12678

PLoS One. 2023 Apr 24;18(4):e0284893. doi: 10.1371/journal.pone.0284893. eCollection 2023.

ABSTRACT

Pregnancy is a condition of broad interest across many medical and health services research domains, but one not easily identified in healthcare claims data. Our objective was to establish an algorithm to identify pregnant women and their pregnancies in claims data. We identified pregnancy-related diagnosis, procedure, and diagnosis-related group codes, accounting for the transition to International Statistical Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) diagnosis and procedure codes, in health encounter reporting on 10/1/2015. We selected women in Merative MarketScan commercial databases aged 15-49 years with pregnancy-related claims, and their infants, during 2008-2019. Pregnancies, pregnancy outcomes, and gestational ages were assigned using the constellation of service dates, code types, pregnancy outcomes, and linkage to infant records. We describe pregnancy outcomes and gestational ages, as well as maternal age, census region, and health plan type. In a sensitivity analysis, we compared our algorithm-assigned date of last menstrual period (LMP) to fertility procedure-based LMP (date of procedure + 14 days) among women with embryo transfer or insemination procedures. Among 5,812,699 identified pregnancies, most (77.9%) were livebirths, followed by spontaneous abortions (16.2%); 3,274,353 (72.2%) livebirths could be linked to infants. Most pregnancies were among women 25-34 years (59.1%), living in the South (39.1%) and Midwest (22.4%), with large employer-sponsored insurance (52.0%). Outcome distributions were similar across ICD-9 and ICD-10 eras, with some variation in gestational age distribution observed. Sensitivity analyses supported our algorithm’s framework; algorithm- and fertility procedure-derived LMP estimates were within a week of each other (mean difference: -4 days [IQR: -13 to 6 days]; n = 107,870). We have developed an algorithm to identify pregnancies, their gestational age, and outcomes, across ICD-9 and ICD-10 eras using administrative data. This algorithm may be useful to reproductive health researchers investigating a broad range of pregnancy and infant outcomes.

PMID:37093890 | DOI:10.1371/journal.pone.0284893

PLoS One. 2023 Apr 24;18(4):e0284928. doi: 10.1371/journal.pone.0284928. eCollection 2023.

ABSTRACT

PURPOSE: COVID-19 pandemic caused an increase in digital screen time, which seemed to increase the prevalence of dry eye symptoms among the population with abnormally high digital screen usage hours. However, there are no reports of dry eye symptoms in school children with high digital usage hours. Therefore, the present study aimed to assess the prevalence of dry eye symptoms and evaluate the associated factors among school children aged 12 to 18 years during the COVID-19 outbreak.

METHODS: Multistage cluster sampling was applied, and six sections of online questionnaires were distributed to selected respondents in November 2021. The odds ratio (OR) with confidence intervals (CIs) for the factors was calculated using binary logistic regression. All statistical significance was determined at p < 0.05.

RESULTS: The findings revealed that 62.5% of 603 students showed symptoms of dry eye (DEQ-5 score ≥ 6). Significant associated factors included being female (adjusted OR (aOR) 1.54; 95% CIs 1.05-2.25), higher-grade student (aOR 1.77; 95% CIs 1.23-2.57), digital screen time use (6 to < 12 hours: aOR 2.00; 95% CIs 1.12-3.57, ≥12 hours: aOR 2.54; 95% CIs 1.39-4.76), and perceived stress (aOR 1.12; 95% CIs 1.08-1.16). The Thai-Perceived Stress Scale-10 scores were positively correlated with the scores on the 5-item dry eye questionnaire (Spearman’s r = 0.38, p-value < 0.01).

CONCLUSION: A high prevalence of dry eye symptoms might be common among school children during the COVID-19 outbreak. Significant risk factors include being female, being a higher-grade level student, prolonged use of digital screens, and perceived stress. However, contact lens use, smoking, and the most common digital device usage patterns were not found to be contributing factors.

PMID:37093868 | DOI:10.1371/journal.pone.0284928

J Chem Phys. 2023 Apr 28;158(16):161101. doi: 10.1063/5.0146711.

ABSTRACT

The chemical potential of adsorbed or confined fluids provides insight into their unique thermodynamic properties and determines adsorption isotherms. However, it is often difficult to compute this quantity from atomistic simulations using existing statistical mechanical methods. We introduce a computational framework that utilizes static structure factors, thermodynamic integration, and free energy perturbation for calculating the absolute chemical potential of fluids. For demonstration, we apply the method to compute the adsorption isotherms of carbon dioxide in a metal-organic framework and water in carbon nanotubes.

PMID:37093149 | DOI:10.1063/5.0146711

J Chem Phys. 2023 Apr 28;158(16):164502. doi: 10.1063/5.0137115.

ABSTRACT

How dense objects, particles, atoms, and molecules can be packed is intimately related to the properties of the corresponding hosts and macrosystems. We present results from extensive Monte Carlo simulations on maximally compressed packings of linear, freely jointed chains of tangent hard spheres of uniform size in films whose thickness is equal to the monomer diameter. We demonstrate that fully flexible chains of hard spheres can be packed as efficiently as monomeric analogs, within a statistical tolerance of less than 1%. The resulting ordered polymer morphology corresponds to an almost perfect hexagonal triangular (TRI) crystal of the p6m wallpaper group, whose sites are occupied by the chain monomers. The Flory scaling exponent, which corresponds to the maximally dense polymer packing in 2D, has a value of ν = 0.62, which lies between the limits of 0.50 (compact and collapsed state) and 0.75 (self-avoiding random walk).

PMID:37092880 | DOI:10.1063/5.0137115

J Chem Phys. 2023 Apr 28;158(16):164501. doi: 10.1063/5.0140951.

ABSTRACT

Clathrate hydrates are crystalline inclusion compounds wherein a water framework encages small guest atoms/molecules within its cavities. Among the others, methane clathrates are the largest fossil fuel resource still available. They can also be used to safely transport gases and can also form spontaneously under suitable conditions plugging pipelines. Understanding the crystallization mechanism is very important, and given the impossibility of experimentally identifying the atomistic path, simulations played an important role in this field. Given the large computational cost of these simulations, in addition to all-atom force fields, scientists considered coarse-grained water models. Here, we have investigated the effect of coarse-graining, as implemented in the water model mW, on the crystallization characteristics of methane clathrate in comparison with the all-atom TIP4P force field. Our analyses revealed that although the characteristics directly depending on the energetics of the water models are well reproduced, dynamical properties are off by the orders of magnitude. Being crystallization a non-equilibrium process, the altered kinetics of the process results in different characteristics of crystalline nuclei. Both TIP4P and mW water models produce methane clathrate nuclei with some amount of the less stable (in the given thermodynamic conditions) structure II phase and an excess of pentagonal dodecahedral cages over the tetrakaidecahedral ones regarding the ideal ratio in structure I. However, the dependence of this excess on the methane concentration in solution is higher with the former water model, whereas with the latter, the methane concentration in solution dependence is reduced and within the statistical error.

PMID:37092879 | DOI:10.1063/5.0140951