Tag: nevin manimala

Brain Commun. 2021 Jun 26;3(3):fcab143. doi: 10.1093/braincomms/fcab143. eCollection 2021.

ABSTRACT

Since amyotrophic lateral sclerosis cases exhibit significant heterogeneity, we aim to investigate the association of lipid composition of plasma and CSF with amyotrophic lateral sclerosis diagnosis, its progression and clinical characteristics. Lipidome analyses would help to stratify patients on a molecular basis. For this reason, we have analysed the lipid composition of paired plasma and CSF samples from amyotrophic lateral sclerosis cases and age-matched non-amyotrophic lateral sclerosis individuals (controls) by comprehensive liquid chromatography coupled to mass spectrometry. The concentrations of neurofilament light chain-an index of neuronal damage-were also quantified in CSF samples and plasma. Amyotrophic lateral sclerosis versus control comparison, in a moderate stringency mode, showed that plasma from cases contains more differential lipids (n = 122 for raw P < 0.05; n = 27 for P < 0.01) than CSF (n = 17 for raw P < 0.05; n = 4 for P < 0.01), with almost no overlapping differential species, mainly characterized by an increased content of triacylglyceride species in plasma and decreased in CSF. Of note, false discovery rate correction indicated that one of the CSF lipids (monoacylglycerol 18:0) had high statistic robustness (false discovery rate-P < 0.01). Plasma lipidomes also varied significantly with the main involvement at onset (bulbar, spinal or respiratory). Notably, faster progression cases showed particular lipidome fingerprints, featured by decreased triacylclycerides and specific phospholipids in plasma, with 11 lipids with false discovery rate-P < 0.1 (n = 56 lipids in plasma for raw P < 0.01). Lipid species associated with progression rate clustered in a relatively low number of metabolic pathways, mainly triacylglyceride metabolism and glycerophospholipid and sphingolipid biosynthesis. A specific triacylglyceride (68:12), correlated with neurofilament content (r = 0.8, P < 0.008). Thus, the present findings suggest that systemic hypermetabolism-potentially sustained by increased triacylglyceride content-and CNS alterations of specific lipid pathways could be associated as modifiers of disease progression. Furthermore, these results confirm biochemical lipid heterogeneity in amyotrophic lateral sclerosis with different presentations and progression, suggesting the use of specific lipid species as potential disease classifiers.

PMID:34396104 | PMC:PMC8361390 | DOI:10.1093/braincomms/fcab143

Brain Commun. 2021 Jun 4;3(3):fcab128. doi: 10.1093/braincomms/fcab128. eCollection 2021.

ABSTRACT

Alternating hemiplegia of childhood is a rare neurodevelopmental disorder caused by ATP1A3 mutations. Some evidence for disease progression exists, but there are few systematic analyses. Here, we evaluate alternating hemiplegia of childhood progression in humans and in the D801N knock-in alternating hemiplegia of childhood mouse, Mashlool, model. This study performed an ambidirectional (prospective and retrospective data) analysis of an alternating hemiplegia of childhood patient cohort (n = 42, age 10.24 ± 1.48 years) seen at one US centre. To investigate potential disease progression, we used linear mixed effects models incorporating early and subsequent visits, and Wilcoxon Signed Rank test comparing first and last visits. Potential early-life clinical predictors were determined via multivariable regression. We also compared EEG background at first encounter and at last follow-up. We then performed a retrospective confirmation study on a multicentre cohort of alternating hemiplegia of childhood patients from France (n = 52). To investigate disease progression in the Mashlool mouse, we performed behavioural testing on a cohort of Mashlool^– mice at prepubescent and adult ages (n = 11). Results: US patients, over time, demonstrated mild worsening of non-paroxysmal disability index scores, but not of paroxysmal disability index scores. Increasing age was a predictor of worse scores: P < 0.0001 for the non-paroxysmal disability index, intellectual disability scale and gross motor scores. Earliest non-paroxysmal disability index score was a predictor of last visit non-paroxysmal disability index score (P = 0.022), and earliest intellectual disability score was a predictor of last intellectual disability score (P = 0.035). More patients with EEG background slowing were noted at last follow-up as compared to initial (P = 0.015). Similar worsening of disease with age was also noted in the French cohort: age was a significant predictor of non-paroxysmal disability index score (P = 0.001) and first and last non-paroxysmal disability index score scores significantly differed (P = 0.002). In animal studies, adult Mashlool mice had, as compared to younger Mashlool mice, (i) worse balance beam performance; (ii) wider base of support; (iii) higher severity of seizures and resultant mortality; and (iv) no increased predisposition to hemiplegic or dystonic spells. In conclusion, (i) non-paroxysmal alternating hemiplegia of childhood manifestations show, on average over time, progression associated with severity of early-life non-paroxysmal disability and age. (ii) Progression also occurs in Mashlool mice, confirming that ATP1A3 disease can lead to age-related worsening. (iii) Clinical findings provide a basis for counselling patients and for designing therapeutic trials. Animal findings confirm a mouse model for investigation of underlying mechanisms of disease progression, and are also consistent with known mechanisms of ATP1A3-related neurodegeneration.

PMID:34396101 | PMC:PMC8361420 | DOI:10.1093/braincomms/fcab128

NAR Genom Bioinform. 2021 Aug 11;3(3):lqab072. doi: 10.1093/nargab/lqab072. eCollection 2021 Sep.

ABSTRACT

Estimating the co-expression of cell identity factors in single-cell is crucial. Due to the low efficiency of scRNA-seq methodologies, sensitive computational approaches are critical to accurately infer transcription profiles in a cell population. We introduce COTAN, a statistical and computational method, to analyze the co-expression of gene pairs at single cell level, providing the foundation for single-cell gene interactome analysis. The basic idea is studying the zero UMI counts’ distribution instead of focusing on positive counts; this is done with a generalized contingency tables framework. COTAN can assess the correlated or anti-correlated expression of gene pairs, providing a new correlation index with an approximate p-value for the associated test of independence. COTAN can evaluate whether single genes are differentially expressed, scoring them with a newly defined global differentiation index. Similarly to correlation network analysis, it provides ways to plot and cluster genes according to their co-expression pattern with other genes, effectively helping the study of gene interactions, becoming a new tool to identify cell-identity markers. We assayed COTAN on two neural development datasets with very promising results. COTAN is an R package that complements the traditional single cell RNA-seq analysis and it is available at https://github.com/seriph78/COTAN.

PMID:34396096 | PMC:PMC8356963 | DOI:10.1093/nargab/lqab072

Turk J Phys Med Rehabil. 2021 May 25;67(2):233-241. doi: 10.5606/tftrd.2021.6887. eCollection 2021 Jun.

ABSTRACT

OBJECTIVES: This study aims to develop measurement tools for assessing patients’ functional status with rheumatoid arthritis (RA) in terms of upper and lower extremity function and to evaluate the tools’ construct validities with classical and modern psychometric approaches.

PATIENTS AND METHODS: Between April 2010 and April 2012, a total of 300 patients with RA (77 males, 223 females; mean age: 52.3±11.5 years; range, 18 to 82 years) who answered items from a range of widely used instruments were included. After examining initial dimensionality with exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and Rasch analysis were used to evaluate the tools’ construct validities. The data-model fit was evaluated with goodness-of-fit (GoF) statistics in CFA, while the tools were examined in terms of item and person fit, unidimensionality and differential item functioning (DIF) from the perspective of Rasch analysis.

RESULTS: According to EFA, two dimensions were identified and named as “self-care-mobility-household activities related to lower extremity” and “self-care-mobility-household activities related to upper extremity” taking into account the factor loadings and the clinical classifications. While the clinical classification was tested with CFA, all items were loaded on their pre-defined dimensions with the factor loadings of ≥0.40 and GoF statistics were within the acceptable ranges. When the “self-care-mobility-household activities related to upper extremity” and “self-care-mobility-household activities related to lower extremity” tools were evaluated via the Rasch analysis, both tools were found to fit the Rasch model expectations, with a mean item fit statistics of -0.528 logit (standard deviation [SD]: 1.365) and -0.213 (SD: 1.168; mean person fit statistics of -0.412 logit (SD: 1.160) and -0.303 logit (SD: 0.859), respectively.

CONCLUSION: For the evaluation of a scale’s construct validity, it is recommended to use the Rasch analysis in tandem with factor analytic methods, as the Rasch analysis explores a scale’s construct validity in terms of item and person fit, DIF and unidimensionality which is the only aspect of the factor analysis.

PMID:34396075 | PMC:PMC8343153 | DOI:10.5606/tftrd.2021.6887

Turk J Phys Med Rehabil. 2021 May 25;67(2):242-249. doi: 10.5606/tftrd.2021.5481. eCollection 2021 Jun.

ABSTRACT

OBJECTIVES: This study aims to investigate the association of COL4A1 and COL4A2 gene polymorphisms with susceptibility to risk of developing cerebral palsy (CP) and severity of CP.

PATIENTS AND METHODS: Between December 2016 and June 2017, a total of 176 patients with CP (101 males, 75 females; mean age 71.8±37.9 months; range, 24 to 184 months) and age-, sex-, and ethnically-matched 178 (90 males, 88 females; mean age 69.3±55.2 months; range, 24 to 214 months) controls were included. Two polymorphisms of COL4A1 (rs1961495) and COL4A2 (rs9521733) genes were typed from genomic deoxyribonucleic acid. Genotype distributions and allelic frequencies were compared between the patient and control groups. Gross Motor Function Classification System, the use of medical drugs, type of involvement, number of affected limbs, accompanying conditions, birth weight, gestational age, and magnetic resonance imaging (MRI) findings were used to evaluate the disease severity and their relationships with the COL4A1 and COL4A2 gene polymorphisms.

RESULTS: There was no statistically significant difference between the groups in terms of genotype distribution and allele frequency of COL4A1 and COL4A2 gene polymorphisms (p>0.05). In addition, there was no relationship between severity of CP and two gene polymorphisms (p>0.05). A significant association was detected between the COL4A2 polymorphism and growth retardation in CP. The TT genotype (57.1%) and T allele (76.2%) were higher, compared to CC (4.8%) and CT genotypes (38.1%) and C allele (23.8%) in patients with CP with growth retardation (p=0.03 for genotype and p=0.01 for allele frequency).

CONCLUSION: These findings suggest that COL4A1 and COL4A2 gene polymorphisms are not associated with susceptibility to CP in a group of Turkish populations, although COL4A2 gene polymorphism may be associated with growth retardation in patients with CP.

PMID:34396076 | PMC:PMC8343154 | DOI:10.5606/tftrd.2021.5481

J Tradit Chin Med. 2021 Aug;41(4):539-545. doi: 10.19852/j.cnki.jtcm.2021.03.006.

ABSTRACT

OBJECTIVE: To evaluate the efficacy of gecko polysaccharide on the cyclophosphamide-induced suppressed immune response in mice.

METHODS: Polysaccharides were extracted from fresh gecko for the first time using an orthogonal method and protein was removed using Sevag reagent (chloroform:N-butanol, 5:1, v/v). The gecko polysaccharide (GPCE) content was determined by the phenol-concentrated sulfuric acid method. An immunocompromised mouse model was established by intraperitoneally injecting cyclophosphamide at 100 mg/kg into 48 mice. The effects of GPCE on immune regulation in mice were assessed by a thymus-spleen index, serum hemolysin levels, and the proliferation of splenic lymphocytes. Spleen cell CD4+, CD8+, and the CD4+/CD8+ ratio were evaluated by flow cytometry and the tumor necrosis factor-α (TNF-α) levels were measured by ELISA.

RESULTS: The optimal extraction process for gecko polysaccharide included a 1:20 ratio of material to liquid (v/v), an extraction temperature of 60 ℃ and a time of 2 h. The polysaccharide content of the extract was 65.74%. GPCE was analyzed by HPLC and primarily contained glucose and small amounts of mannose, rha, and gal. Compared with the model, the thymus index, the spleen index were indices for GPCE increased with dose, whereas the high and medium groups exhibited significant differences (P < 0.05, P < 0.01). Higher doses of GPCE increased serum TNF-α levels and there was a significant difference between the medium and high GPCE doses and the model (P < 0.05, P < 0.01); The number of CD4+ cells and the CD4+/CD8+ ratio in the gecko polysaccharide group were increased (P < 0.05) and there was no statistical difference in the number of CD8+ cells in the gecko polysaccharide group (P > 0.05); The high GPCE dose significantly increased the level of serum hemolysin (P < 0.01).

CONCLUSIONS: Gecko polysaccharide significantly improved the suppressed immune response induced by cyclophosphamide in mice and promoted the secretion of tumor necrosis factor. The mechanism of gecko polysaccharide as an antitumor agent warrants further study.

PMID:34392646 | DOI:10.19852/j.cnki.jtcm.2021.03.006

Trends Psychiatry Psychother. 2021 Aug 11. doi: 10.47626/2237-6089-2021-0279. Online ahead of print.

ABSTRACT

INTRODUCTION: There are several negative impacts on the physical and mental health of people presenting internet addiction, especially for the development of mood disorders, such as depression.

OBJECTIVE: The aim of the study was to evaluate the association between internet addiction and depressive symptoms, as well as to test the mediating role of physical activity in this association.

METHODS: A cross-sectional study was conducted among undergraduate students from three universities (one private and two public institution) from southern Brazil. Depressive symptoms were measured with the Beck Depression Inventory (BDI-21), internet addiction with the Internet Addiction Test (IAT-20) and physical activity was assessed with the International Physical Activity Questionnaire (IPAQ – short version). Poisson regression and the Karlson-Holm-Breen mediation method were used to the statistical analyses.

RESULTS: We have observed a dose-response relation between internet addiction and depressive symptoms. Levels of physical activity mediated the association between moderate internet addiction and depressive symptoms, accounting for 10.7% of the effect observed.

CONCLUSION: Internet addiction can be detrimental to individuals’ health, and contribute to the development of depressive symptoms. Along with psychological and pharmacological therapies, prescription of physical activities are recommended.

PMID:34392666 | DOI:10.47626/2237-6089-2021-0279

Trends Psychiatry Psychother. 2021 Apr-Jun;43(2):126-133. doi: 10.47626/2237-6089-2020-0022.

ABSTRACT

OBJECTIVE: Breast cancer is the most common cancer in women worldwide. Many of these patients suffer from multiple psychological symptoms. The present study aimed to investigate the impact of acceptance and commitment therapy (ACT) on depression, pain acceptance, and psychological flexibility in married women with breast cancer.

METHODS: The present study was a pre- and post-test clinical trial with intervention and control groups. The research population consisted of women with breast cancer referred to the Ayatollah Yasrebi and Shahid Beheshti Hospitals in Kashan in 2018. Through a purposive sampling method, 40 women were selected and randomly divided into two groups, namely, intervention (n = 20) and control (n = 20). The applied tools included the Depression, Anxiety and Stress Scale (DASS-21), Chronic Pain Acceptance Questionnaire 8 (CPAQ-8), and Acceptance and Action Questionnaire – II (AAQ-II). Data were analyzed by SPSS 16 using descriptive statistics and analysis of variance (ANOVA).

RESULTS: The results showed that ACT treatment significantly reduced the mean scores of depression compared to the control group (F = 107.72, p < 0.001). The mean scores of pain acceptance (F = 9.58, p < 0.05) and psychological flexibility (F = 10.61, p < 0 .05) significantly increased in comparison with the control group.

CONCLUSION: ACT can be considered as an effective therapeutic approach to reduce depression and increase pain acceptance and psychological flexibility in women with breast cancer. These changes appear to be due to improved acceptance of thoughts and feelings associated with cancer and increased psychological flexibility, which is the primary goal of ACT treatment.

CLINICAL TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT), IRCT20190518043620N1.

PMID:34392667 | DOI:10.47626/2237-6089-2020-0022

Int J Biostat. 2021 Aug 16. doi: 10.1515/ijb-2020-0144. Online ahead of print.

ABSTRACT

The timings of visits in observational longitudinal data may depend on the study outcome, and this can result in bias if ignored. Assessing the extent of visit irregularity is important because it can help determine whether visits can be treated as repeated measures or as irregular data. We propose plotting the mean proportions of individuals with 0 visits per bin against the mean proportions of individuals with >1 visit per bin as bin width is varied and using the area under the curve (AUC) to assess the extent of irregularity. The AUC is a single score which can be used to quantify the extent of irregularity and assess how closely visits resemble repeated measures. Simulation results confirm that the AUC increases with increasing irregularity while being invariant to sample size and the number of scheduled measurement occasions. A demonstration of the AUC was performed on the TARGet Kids! study which enrolls healthy children aged 0-5 years with the aim of investigating the relationship between early life exposures and later health problems. The quality of statistical analyses can be improved by using the AUC as a guide to select the appropriate analytic outcome approach and minimize the potential for biased results.

PMID:34392639 | DOI:10.1515/ijb-2020-0144

J Tradit Chin Med. 2021 Aug;41(4):507-514. doi: 10.19852/j.cnki.jtcm.2021.03.002.

ABSTRACT

OBJECTIVE: To use evidence-based medicine to systematically evaluate the effectiveness and safety of acupuncture therapy for improving anorexia in tumor patients.

METHODS: We queried the China National Knowledge Infrastructure Database (CNKI), China Science and Technology Journal Database (VIP), Wanfang Data, PubMed, Cochrane Library, and Embase databases to identify reports of randomized controlled trials (RCTs) that applied acupuncture therapy to improve anorexia in tumor patients, and used Rev Man 5.3 software to conduct a Meta-analysis of the effective rate, appetite score, Karnofsky Performance Status (KPS) score, Functional Assessment of Anorexia/Cachexia Therapy (FAACT) appetite scale, and body weight in each study. Subgroup analysis was conducted based on whether radiotherapy or chemotherapy were also administered.

RESULTS: A total of 10 RCTs were included with a total of 648 patients, including 343 patients in the treatment group and 305 patients in the control group. The Meta-analysis results showed that the clinical efficacy, appetite score, KPS score, and FAACT score of the treatment group (which received acupuncture to improve appetite) were better than those of the control group, and the difference was statistically significant (P < 0.05); however, there was no statistically significant difference in body weight between the treatment group and the control group (P > 0.05). The results of the subgroup analysis showed that the effective rate and appetite score for patients with long-term and chronic loss of appetite who underwent acupuncture were better than those of the control group, and the difference was statistically significant (P < 0.05).

CONCLUSIONS: Acupuncture therapy has good efficacy and safety in the treatment of anorexia in tumor patients, and it also has good efficacy and safety for long-term and chronic loss of appetite. The reliability and stability of the above results need to be confirmed by high-quality RCTs with larger sample sizes.

PMID:34392642 | DOI:10.19852/j.cnki.jtcm.2021.03.002