Tag: nevin manimala

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

Asian Pac J Cancer Prev. 2023 May 1;24(5):1731-1735. doi: 10.31557/APJCP.2023.24.5.1731.

ABSTRACT

OBJECTIVE: Our study aimed to characterize alteration in the immunohistochemical expression of estrogen, progesterone and androgen receptor in the tumour cells of primary pleomorphic adenomas and recurrent pleomorphic adenomas.

METHODS: A retrospective study of data including 30 cases of primary pleomorphic adenomas (PA) without recurrences and 15 cases of recurrent pleomorphic adenomas were examined (RPA). RPA included 8 males and 7 females. Immunohistochemical expression of estrogen, progesterone and androgen receptor was examined in the selected cases. The percentage of slides was semi-quantitatively assessed by two independent observers and scores were given. The statistical analysis included the use of descriptive statistics and proportional frequencies.

RESULTS: AR expression was identified in 12 (40. %) out of 30 cases of (PA) pleomorphic adenomas and 7 of 15 cases recurrent pleomorphic adenomas (RPA) (46 %). The results showed that ER and PR expression were negative in PA and RPA.

CONCLUSION: Androgen receptors might have role in pathogenesis of PA and RPA. Estrogen and progesterone receptors have no role in development of recurrent pleomorphic salivary adenoma.

PMID:37247295 | DOI:10.31557/APJCP.2023.24.5.1731

Asian Pac J Cancer Prev. 2023 May 1;24(5):1717-1723. doi: 10.31557/APJCP.2023.24.5.1717.

ABSTRACT

OBJECTIVE: The purpose of this study was to assess the immune response and malondialdehyde levels in irradiated rats supplemented with Curcuma xanthorriza Roxb extract as a candidate for mitigating radiation exposure.

METHODS: Twenty-four male Wistar rats were grouped into eight treatment groups, then Curcuma xanthorrhiza Roxb extract was administered orally and irradiated at 6 Gy. Measurement of rats IL-6 and INF-γ was performed using a sandwich ELISA Kit, while the MDA concentration was quantified according to the method of Wills (1971). The statistical test is determined by one way ANOVA test. P-value <0.05 was considered statistically significant.

RESULT: The concentration of IL-6 in all groups showed no statistically significant difference (P=0.18). There was an increase in the concentration of IL-6 in the group of rats irradiated with 6 Gy for 7 days and 14 days. Meanwhile, the INF-γ concentration also showed no significant results in all treatment groups (P=0.28). The average of MDA concentration showed a significant difference in the liver and spleen of irradiated rats at 6 Gy for 14 days compared to the control (0.044 nmol/mg vs 0.008 nmol/mg, P=0.03 and 0.032 nmol/mg vs 0.014 nmol/mg, P=0.05, respectively).

CONCLUSION: The administration of Curcuma xanthorriza Xorb extract was able to reduce MDA concentrations in the liver and spleen although not statistically significant. In addition, exposure to ionizing radiation at a dose of 6 Gy significantly increased lipid peroxidation in the liver and spleen by 5.5 times and 2.3 times, respectively.

PMID:37247293 | DOI:10.31557/APJCP.2023.24.5.1717

Asian Pac J Cancer Prev. 2023 May 1;24(5):1695-1700. doi: 10.31557/APJCP.2023.24.5.1695.

ABSTRACT

OBJECTIVE: To evaluate the anti-carcinogenic effect of Centella Asiatica on to evaluate the Anti-Carcinogenic Effect of Centella Asiatica on Oral Cancer Cell Line oral cancer cell line.

MATERIALS AND METHODS: Oral Cancer cell line and normal oral keratinocyte cell line were procured.Centella asiatica extract was prepared. The cells were then subjected to the test herbal specimens -Centella asiatica extract in succeeding concentrations of 25 µg/ml, 50 µg/ml, 100 µg/ml at time intervals of 24,48 and 72 hours. Cisplatin (2 µg/ml, 4 µg/ml, 6 µg/ml, 8 µg/ml) was used as a positive control. This experiment was done in triplets.

RESULTS: The study revealed that the p values were less than 0.05 at concentration 12.5µg/ml, 25µg/ml, 50 µg/ml,100 µg/ml and time period of 24hrs,48hrs,72hrs, thus implying that at these concentrations and time period, the obtained data were statistically significant, thus indicating that there is a statistically significantly decreases in the viable cells as the concentration of the drug as a time period increases The results reveals that centella asiatica possess potential effect of anti-carcinogenic, effect when compared to positive control (Cisplatin).

CONCLUSION: The current study reveals that Centella asiatica has an potential anti-carcinogenic effect on oral cancer cell line. So this can be used to treat oral cancer with minimal crippling as compared with allopathic drugs.

PMID:37247290 | DOI:10.31557/APJCP.2023.24.5.1695

Asian Pac J Cancer Prev. 2023 May 1;24(5):1677-1685. doi: 10.31557/APJCP.2023.24.5.1677.

ABSTRACT

AIM: Dose calculation accuracy between Anisotropic Analytical Algorithm (AAA) and Acuros XB (AXB) for various megavoltage (MV) photon beams for both flattening filter (FF) and flattening filter free (FFF) beams and to validate the accuracy of these dose calculations using inhomogeneous phantom in volumetric modulated arc therapy (VMAT).

MATERIAL AND METHODS: A Cheese Phantom having 20 holes that can be filled with all virtual water plugs or set of density calibration plugs was used for VMAT planning using two different algorithms using either single or double arc. Further phantom was used irradiate plan in linear accelerator and the point doses measured using a 0.053 cc A1SL ionization chamber along electrometer . Different plans, cylindrical shape, C-shaped and donut targets were planned 6MV, 10MV, 6FFF MV and 10FFF MV beam energy.

RESULT: The minimum average mean dose difference was 1.2% for PTV structures between AAA and AXB (p=0.02). Apart from these structures, the following density plugs have a more than 2% difference in maximum dose with statistical significance. (i) Solid water (MD=6.1%, p=0.016), (ii) Bone 200 (2.3%, p=0.029), (iii) CB_30% (MD=2.4%, p=0.050) and (iv) Cortical bone (MD=4.3%, p=0.018). In 6MV FFF and 10 MV FFF plans, the difference between AAA and AXB was not statistically significant (Fig 3). The Conformity index for the AAA less than that of AXB, in all energies and for all the PTVs. The CI was better in AXB than AAA, but the CI was not having much variation due to changes in beam energies, particularly for Cylinder shaped PTV.

CONCLUSION: All combinations of beam energy AAA showed higher values in the maximum dose than the Acuros XB, except for the lung insert. Nonetheless, AAA showed a higher mean dose than the Acuros XB. Differences between these two algorithms for most of the beam energies are minimal.

PMID:37247288 | DOI:10.31557/APJCP.2023.24.5.1677