Category: Nevin Manimala

Cytokine. 2023 May 27;168:156231. doi: 10.1016/j.cyto.2023.156231. Online ahead of print.

ABSTRACT

BACKGROUND: Burn injury is a sudden and traumatic injury that affects a large part of the population worldwide, who are placed at high risk of developing hypertrophic scars (HTS). HTS are a fibrotic scar resulting in painful contracted and raised scarring, affecting mobility in joints and work life, as well as cosmetically. The aim of this research was to enhance our understanding of the systematic response of monocytes and cytokines in wound healing after burn injury, in order to develop novel approaches to prevention and treatment of HTS.

METHODS: Twenty-seven burn patients and thirteen healthy individuals were recruited in this study. Burn patients were stratified by burn total body surface area (TBSA). Peripheral blood samples were taken post-burn injury. Serum and peripheral blood mononuclear cells (PBMCs) were separated from the blood samples. This research investigated cytokines IL-6, IL-8, IL1RA, IL-10, and chemokine pathways SDF-1/CXCR4, MCP-1/CCR2, RANTES/CCR5 during the wound healing process in burn patients with varying severity of injuries by using enzyme-linked immunosorbent assays. PBMCs were stained for monocytes and the chemokine receptors by flow cytometry. Statistical analysis was done by one-way ANOVA with a Tukey correction, and regression analysis was performed using Pearson’s Correlation analysis.

RESULTS: The CD14⁺CD16^– monocyte subpopulation is larger in patients who developed HTS at 4-7 days. The CD14⁺CD16⁺ monocyte subpopulation is smaller in the first week of injury, where it is similar after 8 days. Burn injury increased CXCR4, CCR2, and CCR5 expressions in CD14⁺ CD16⁺ monocytes. Increases in MCP-1 at 0-3 days after burn injury was positively correlated with burn severity. IL-6, IL-8, RANTES, and MCP-1 significantly increased with increasing burn severity.

CONCLUSIONS: Monocytes and their chemokine receptors, as well as systemic levels of cytokines in wound healing of burn patients and scar development will require ongoing assessment to enhance our understanding of the abnormal wound healing after burn injury.

PMID:37247448 | DOI:10.1016/j.cyto.2023.156231

Water Res. 2023 May 21;240:120110. doi: 10.1016/j.watres.2023.120110. Online ahead of print.

ABSTRACT

There has been a significant increase in antimicrobial agents (AAs) usage, globally – however the relative consumption is unevenly distributed between nations. Inappropriate use of antibiotics can harbour inherent antimicrobial resistance (AMR); therefore, it is important to understand and monitor community-wide prescribing and consumption behaviours throughout different communities around the world. Wastewater-Based Epidemiology (WBE) is a novel tool enabling low cost and large scale studies focussed on AA usage patterns. The back-calculation of community antimicrobial intake was performed from quantities measured in municipal wastewater and informal settlement discharge in the city of Stellenbosch, utilising WBE. Seventeen antimicrobials, and their human metabolites, were evaluated, in concordance with prescription records corresponding to the catchment region. The proportional excretion, biological/chemical stability, and method recovery of each analyte were all crucial factors in the efficacy of the calculation. Mass per day measurements were normalised to the catchment area via population estimates. Municipal wastewater treatment plant population estimates were used to normalise the wastewater samples and prescription data (mg/day/1000 inhabitants). Population estimates for the informal settlements were less accurate due to a lack of reliable sources that were relevant to the sampling time period. Both mass loads and normalised loads suggested higher than average usage throughout the settlements, relative to municipal wastewater. This was seen most prominently in emtricitabine and lamivudine; but also, sulfamethoxazole, trimethoprim, sulfadiazine, clindamycin, ciprofloxacin, ofloxacin, and doxycycline. Urban water fingerprinting (UWF) data triangulation with prescription datasets showed good correlations for several antimicrobial agents (AAs) (e.g., clindamycin, clarithromycin, ofloxacin, and doxycycline). It also revealed discrepancies in usage for some compounds (e.g., tetracycline and sulfapyridine). This might be linked with a lack of pharma compliance in prescription datasets; erroneous association of prescription boundaries with the sewerage catchment; and/or uncertainties within the sewerage catchment (e.g., population estimations). The UWF tool provided a comprehensive overview of multiclass AAs usage, both prescription and over-the counter. For example, tetracycline was not reported in available prescription statistics, but was detected at an average of 18.4 mg/day/1000inh; and no antiviral prescriptions were obtained, but emtricitabine and lamivudine were quantified at 2415.4 and 144.4 mg/day/1000inh, respectively. A lack of clarity regarding prescriptions and a lack of inclusion of several critical (often over-the-counter) medications in public health databases makes WBE a useful and comprehensive epidemiology tool for tracking pharma usage within a catchment.

PMID:37247434 | DOI:10.1016/j.watres.2023.120110

Percept Mot Skills. 2023 May 29:315125231179591. doi: 10.1177/00315125231179591. Online ahead of print.

ABSTRACT

Previous mastery motivational climate (MMC) movement interventions have enhanced fundamental motor skill (FMS) competence across diverse groups of preschool-age children. Yet, an adequate intervention length has not been established. Our purposes in this study were to (i) compare FMS competence in preschool children across two doses of MMC interventions, and (ii) describe changes in children’s FMS ‘mastery’ across doses. We used secondary data analysis from a larger MMC intervention study in which 32 children (M_age = 4.4) received FMS testing (TGMD-3) at the mid-point of intervention and at post-intervention. A two-way mixed ANOVA with Group as the independent variable and FMS competence across three Time points as the repeated measure was significant for both Group and Time main effects for locomotor and ball skill competences separately. There was a statistically significant interaction between Group and Time on locomotor (p = .02) and ball skills (p < .001). Both groups showed significant improvements in their locomotor skills at each time point, but the intervention group improved faster than the comparison group. For ball skills, only the MMC group significantly improved by mid-intervention, and the comparison group showed significant improvements from pre-to post-intervention only. Children in this study were most likely to show mastery in running first, followed by sliding at mid-intervention. Few children mastered skipping, galloping, and hopping across the study. For ball skills, overhand and underhand throwing were more likely to be mastered, and few children mastered one and two-hand striking across the study. Collectively, these findings suggest that duration of instructional minutes may not be the most effective proxy for identifying a dose-response relationship of MMC intervention. Moreover, focusing on the patterns of skill mastery can help inform researchers and practitioners as to how to allocate instructional time during MMC interventions to optimize FMS competence for young children.

PMID:37247423 | DOI:10.1177/00315125231179591

Age Ageing. 2023 May 1;52(5):afad080. doi: 10.1093/ageing/afad080.

ABSTRACT

BACKGROUND: midlife hearing loss is a potentially modifiable risk factor for dementia. Addressing comorbid hearing loss and cognitive impairment in services for older adults may offer opportunities to reduce dementia risk.

OBJECTIVE: to explore current practice and views amongst UK professionals regarding hearing assessment and care in memory clinics and cognitive assessment and care in hearing aid clinics.

METHODS: national survey study. Between July 2021 and March 2022, we distributed the online survey link via email and via QR codes at conferences to professionals working in National Health Service (NHS) memory services and audiologists working in NHS and private adult audiology services. We present descriptive statistics.

RESULTS: 135 professionals working in NHS memory services and 156 audiologists (68% NHS, 32% private sector) responded. Of those working in memory services, 79% estimate that >25% of their patients have significant hearing difficulties; 98% think it useful to ask about hearing difficulties and 91% do so; 56% think it useful to perform a hearing test in clinic but only 4% do so. Of audiologists, 36% estimate that >25% of their older adult patients have significant memory problems; 90% think it useful to perform cognitive assessments, but only 4% do so. Main barriers cited are lack of training, time and resources.

CONCLUSIONS: although professionals working in memory and audiology services felt addressing this comorbidity would be useful, current practice varies and does not generally address it. These results inform future research into operational solutions to integrating memory and audiology services.

PMID:37247401 | DOI:10.1093/ageing/afad080

Genome Biol Evol. 2023 May 29:evad096. doi: 10.1093/gbe/evad096. Online ahead of print.

ABSTRACT

The determination of the last common ancestor (LCA) of a group of species plays a vital role in evolutionary theory. Traditionally, an LCA is inferred by the rooting of a fully resolved species tree. From a theoretical perspective, however, inference of the LCA amounts to the reconstruction of just one branch – the root branch – of the true species tree, and should therefore be a much easier task than the full resolution of the species tree. Discarding the reliance on a hypothesised species tree and its rooting leads us to re-evaluate what phylogenetic signal is directly relevant to LCA inference, and to recast the task as that of sampling the total evidence from all gene families at the genomic scope. Here we reformulate LCA and root inference in the framework of statistical hypothesis testing and outline an analytical procedure to formally test competing a-priori LCA hypotheses and to infer confidence sets for the earliest speciation events in the history of a group of species. Applying our methods to two demonstrative datasets we show that our inference of the opisthokonta LCA is well in agreement with the common knowledge. Inference of the proteobacteria LCA shows that it is most closely related to modern Epsilonproteobacteria, raising the possibility that it may have been characterized by a chemolithoautotrophic and anaerobic life-style. Our inference is based on data comprising between 43% (opisthokonta) and 86% (proteobacteria) of all gene families. Approaching LCA inference within a statistical framework renders the phylogenomic inference powerful and robust.

PMID:37247390 | DOI:10.1093/gbe/evad096

Brain. 2023 May 29:awad183. doi: 10.1093/brain/awad183. Online ahead of print.

ABSTRACT

Intraneuronal accumulation of misfolded α-synuclein is the pathological hallmark of Parkinson’s disease and dementia with Lewy bodies, often co-occurring with variable degrees of Alzheimer’s disease related neuropathology. Genetic association studies have successfully identified common variants associated with disease risk and phenotypic traits in Lewy body disease, yet little is known about the genetic contribution to neuropathological heterogeneity. Using summary statistics from Parkinson’s disease and Alzheimer’s disease genome wide association studies we calculated polygenic risk scores and investigated the relationship with Lewy, amyloid-β, and tau pathology. Associations were nominated in neuropathologically defined samples with Lewy body disease from the Netherlands Brain Bank (n = 217 and followed up in an independent sample series from the Mayo Clinic Brain Bank (n = 394). We also generated stratified polygenic risk scores based on single-nucleotide polymorphisms annotated to eight functional pathways or cell types previously implicated in Parkinson’s disease and assessed for association with Lewy pathology in subgroups with and without significant Alzheimer’s disease co-pathology. In an ordinal logistic regression model the Alzheimer’s disease polygenic risk score was associated with concomitant amyloid-β and tau pathology in both cohorts. Moreover, both cohorts showed a significant association between lysosomal pathway polygenic risk and Lewy pathology, which was more consistent than the association with a general Parkinson’s disease risk score and specific to the subset of samples without significant concomitant Alzheimer’s disease related neuropathology. Our findings provide proof of principle that the specific risk alleles a patient carries for Parkinson’s and Alzheimer’s disease also influence key aspects of the underlying neuropathology in Lewy body disease. The interrelations between genetic architecture and neuropathology are complex, as our results implicate lysosomal risk loci specifically in the subset of samples without Alzheimer’s disease co-pathology. Our findings hold promise that genetic profiling may help predict the vulnerability to specific neuropathologies in Lewy body disease, with potential relevance for the further development of precision medicine in these disorders.

PMID:37247383 | DOI:10.1093/brain/awad183

West Afr J Med. 2023 May 27;40(5):553-561.

ABSTRACT

BACKGROUND: Inhalational therapy is the cornerstone in the management of chronic obstructive pulmonary disease (COPD) patients. Patients’ peak inspiratory flow impacts effective dry powder inhaler (DPI) delivery and management outcome.

OBJECTIVE: This study assessed peak inspiratory flow rates (PIFR) and determined the factors associated with suboptimal inspiratory flow rates among COPD patients.

METHODS: A descriptive cross-sectional study was conducted among 60 participants (30 stable COPD patients and 30 age-and-sex matched controls). Socio-demographic characteristics was obtained and spirometry was done for all participants. PIFR assessment was done using the In-Check Dial Meter and was categorized as suboptimal (< 60L/min) or optimal (≥ 60L/min). P values less than 0.05 were taken as statistically significant.

RESULTS: Mean age of the COPD patients and healthy controls were both 67.8 ± 10.3 years, with 53.3% being females. Post-bronchodilation FEV 1/FVC% for COPD patients was 54.15 ± 11.27%. The mean PIFR among COPD patients was significantly lower than that of healthy controls, in all DPIs simulated, especially for Clickhaler (46.2±13.4 vs 60.5±11.4L/min, p<0.001). A significant proportion of COPD patients had suboptimal PIFR, in the simulated resistances against Clickhaler and Turbuhaler (70% vs 80%; p<0.001). Older age, shorter height and low BMI were associated with suboptimal PIFR among COPD patients. However, independent predictors of suboptimal PIFR were BMI, PEFR, FEV1% and FVC%.

CONCLUSION: Suboptimal PIFR was found in a significant number of COPD patients when compared with healthy respondents. Routine assessment using In-Check Dial meter should be done to determine the suitability of dry powder inhalers for patients with COPD.

PMID:37247343

West Afr J Med. 2023 May 27;40(5):546-552.

ABSTRACT

BACKGROUND: Inappropriate health-seeking behaviour has been associated with unfavourable health outcomes. This study determined the association between socio-demographic characteristics and health-seeking behaviour and the association between health-seeking behaviour and health outcomes of patients attending the health insurance clinic of a tertiary hospital.

METHODS: The study was carried out between July and November 2021, involving patients who attended the NHIS clinic, of Ekiti State University Teaching Hospital, Ado Ekiti, between 2009 and 2018. The records were reviewed, and data about their socio-demographic characteristics, the period between when symptoms started and the time of presentation in the clinic with the outcome of the patient, were extracted and analysed.

RESULTS: A total of 12,200 patients were seen within the period under review. Females were 51.1%, Yorubas were 92.0%, Christians 95.5%, 51.1% had tertiary education, and 32.5% had primary education. Looking at timely reporting, 58% reported at the clinic 48 hours after symptoms while 23% reported within 24 hours. Of those who presented within 24 hours, 13.1% were admitted compared to 2.2% of those who presented after 48 hours. The association between timeliness of reporting and outcome was statistically significant with p value < 0.05.

CONCLUSION: The severity of the illness determined the timeliness of presentation at the Clinic despite being insured. Social and behavioural change intervention is recommended for attitudinal change to improve health-seeking behaviour.

PMID:37247332

Asian Pac J Cancer Prev. 2023 May 1;24(5):1797-1808. doi: 10.31557/APJCP.2023.24.5.1797.

ABSTRACT

BACKGROUND: Prostate-specific membrane antigen (PSMA) was first noticed in prostate cancer cells, thereafter, It has been found in the endothelial cells of neovasculature in a variety of tumors, but not in normal vascular endothelium, This specificity makes PSMA an ideal molecule for vascular targeting in Cancer theranostics (i.e., combined diagnostic and therapeutic).

OBJECTIVES: The objective of this study was to evaluate the immunohistochemical (IHC) expression of PSMA in the neovasculature (identified by CD 31) of high-grade gliomas (HGGs) and to Correlate PSMA IHC expression in HGGs with clinicopathological features, to detect its possible role in tumor angiogenesis, where PSMA can be used as a future diagnostic and therapeutic target.

MATERIALS AND METHODS: This retrospective study included a total of 69 archived, formalin-fixed, paraffin-embedded tissue blocks of HGGs, including 52 cases classified as WHO grade IV (75.4%) and 17 cases as WHO grade III (24.6%). The samples were immunohistochemically analyzed for PSMA expression (in both TMV and parenchymal tumor cells) which was assessed using the composite PSMA immunostaining score. A score (0) was considered negative while scores 1-7 were considered positive (1-4, 5-6, or 7; weak, moderate, or strong respectively).

RESULTS: PSMA is expressed specifically and significantly in endothelial cells of tumor microvessels (TMV) of HGGs, A statistically significant relationship was detected between PSMA IHC expression in both TMV and in parenchymal tumor cells (TC) and various glioma subtypes (P-value < 0.05 and <0.001 respectively). Positive PSMA immunostaining in TMV was detected in all anaplastic ependymoma cases and in near all cases of classic GB and GB with oligodendroglial features more than other subtypes, with P-value specifically for PSMA positivity/negativity in TMV statistically significant (0.022). While for Tumor cells, Positive PSMA immunostaining was detected in all anaplastic ependymoma, most anaplastic astrocytoma and classic GB cases in contrary to other variants, with P-value statistically extremely significant (< 0.001). Comparing PSMA IHC expression in TMV and its expression in TC, it was significantly expressed in TMV of 82.7% versus TC of 51.9% of grade IV cases. Likewise, in GB with oligodendroglial features and gliosarcoma, the majority of cases showed positive staining in their TMV [8/8 (100%), 9/13 (69.2%) respectively], and, the reverse occurs in tumor cells where the majority of cases did NOT show staining in the tumor cells for PSMA (5/8 (62.5%), 11/13 (84.6%) of cases respectively), which was statistically significant (P-value ≤ 0.05) besides the significant difference in the pattern of staining according to composite PSMA scoring (P-value ≤ 0.05).

CONCLUSION: PSMA has a possible role in tumor angiogenesis, therefore it might be considered a potential promising endothelial target for Cancer theranostics with PSMA-based agents, in addition, PSMA was expressed significantly in TC of HGGs, thus, it appears to be involved in biologic behavior, carcinogenesis and tumor progression.

PMID:37247303 | DOI:10.31557/APJCP.2023.24.5.1797

Asian Pac J Cancer Prev. 2023 May 1;24(5):1737-1741. doi: 10.31557/APJCP.2023.24.5.1737.

ABSTRACT

OBJECTIVE: This study aimed to examine the expression of Histone H3.3 glycine 34 to tryptophan (G34W) mutant protein in Giant Cell Tumor of Bone (GCTB).

METHODS: This analytic observation research used a cross-sectional study design on 71 bone tumors. The cases involved 54 tissue samples diagnosed as GCBT. It was divided into GCTB primer (n=37), recurrent GCTB (n=5), GCTB with metastasis (n=9), and malignant GCTB (n=3). There were 17 samples mimics of GCTB also tested, including chondroblastoma (n=1), giant cell reparative granuloma (n=2), giant cell of tendon sheath (n=7), chondromyxoid fibroma (n=2), aneurysmal bone cyst (n=2), and giant cell-rich osteosarcoma (n=3). The Immunohistochemistry was used to evaluate the expression of G34W-mutated protein in these bone tumors.

RESULT: The representation H3.3 (G34W) was expressed in the nuclei of mononuclear stromal cells but not stained on osteoclast-like giant cells. This study was analyzed by the Chi-square test, Fisher’s test, specificity test, and sensitivity test. We obtained p = 0.001 for Histone H3.3 (G34W) mutant expression in GCTB vs Non-GCTB. Statistically, there was no significant difference in the expression level of Histone H3.3 (G34W) in the GCTB and its variants p-value = 0.183. We also obtained that the specificity of Histone H3.3 expression on GCTB was 100% and the sensitivity of Histone H3.3 on GCTB was 77.8%.

CONCLUSION: Histon H3.3 mutant as a mutated driver gene in an Indonesian GCTB can assist to diagnose GCTB and compare it from other bone tumors.

PMID:37247296 | DOI:10.31557/APJCP.2023.24.5.1737