Tag: nevin manimala

Chin Med. 2023 Jul 28;18(1):89. doi: 10.1186/s13020-023-00782-0.

ABSTRACT

BACKGROUND: Evaluating traditional Chinese medicine (TCM) quality is a powerful method to ensure TCM safety. TCM quality evaluation methods primarily include characterization evaluations and separate physical, chemical, and biological evaluations; however, these approaches have limitations. Nevertheless, researchers have recently integrated evaluation methods, advancing the emergence of frontier research tools, such as TCM quality markers (Q-markers). These studies are largely based on biological activity, with weak correlations between the quality indices and quality. However, these TCM quality indices focus on the individual efficacies of single bioactive components and, therefore, do not accurately represent the TCM quality. Conventionally, provenance, place of origin, preparation, and processing are the key attributes influencing TCM quality. In this study, we identified TCM-attribute-based quality indices and developed a comprehensive multiweighted multi-index-based TCM quality composite evaluation index (QCEI) for grading TCM quality.

METHODS: The area of origin, number of growth years, and harvest season are considered key TCM quality attributes. In this study, licorice was the model TCM to investigate the quality indicators associated with key factors that are considered to influence TCM quality using multivariate statistical analysis, identify biological-evaluation-based pharmacological activity indicators by network pharmacology, establish real quality indicators, and develop a QCEI-based model for grading TCM quality using a machine learning model. Finally, to determine whether different licorice quality grades differently reduced the inflammatory response, TNF-α and IL-1β levels were measured in RAW 264.7 cells using ELISA analysis.

RESULTS: The 21 quality indices are suitable candidates for establishing a method for grading licorice quality. A computer model was established using SVM analysis to predict the TCM quality composite evaluation index (TCM QCEI). The tenfold cross validation accuracy was 90.26%. Licorice diameter; total flavonoid content; similarities of HPLC chromatogram fingerprints recorded at 250 and 330 nm; contents of liquiritin apioside, liquiritin, glycyrrhizic acid, and liquiritigenin; and pharmacological activity quality index were identified as the key indices for constructing the model for evaluating licorice quality and determining which model contribution rates were proportionally weighted in the model. The ELISA analysis results preliminarily suggest that the inflammatory responses were likely better reduced by premium-grade than by first-class licorice.

CONCLUSIONS: In the present study, traditional sensory characterization and modern standardized processes based on production process and pharmacological efficacy evaluation were integrated for use in the assessment of TCM quality. Multidimensional quality evaluation indices were integrated with a machine learning model to identify key quality indices and their corresponding weight coefficients, to establish a multiweighted multi-index and comprehensive quality index, and to construct a QCEI-based model for grading TCM quality. Our results could facilitate and guide the development of TCM quality control research.

PMID:37501143 | DOI:10.1186/s13020-023-00782-0

Malar J. 2023 Jul 27;22(1):218. doi: 10.1186/s12936-023-04649-5.

ABSTRACT

BACKGROUND: Malaria, transmitted by the bite of infective female Anopheles mosquitoes, remains a global public health problem. The presence of invasive Anopheles stephensi, capable of transmitting Plasmodium vivax and Plasmodium falciparum, was first reported in Ethiopia in 2016. The ecology of this mosquito species differs from that of Anopheles arabiensis, the primary malaria vector in Ethiopia. This study aimed to evaluate the efficacy of selected insecticides, which are used in indoor residual spraying (IRS) and selected long-lasting insecticidal nets (LLINs) for malaria vector control against adult An. stephensi.

METHODS: Anopheles stephensi mosquitoes were collected as larvae and pupae from Awash Subah Kilo Town and Haro Adi village, Ethiopia. Adult female An. stephensi, reared from larvae and pupae collected from the field, aged 3-5 days were exposed to impregnated papers of IRS insecticides (propoxur 0.1%, bendiocarb 0.1%, pirimiphos-methyl 0.25%), and insecticides used in LLINs (alpha-cypermethrin 0.05%, deltamethrin 0.05% and permethrin 0.75%), using diagnostic doses and WHO test tubes in a bio-secure insectary at Aklilu Lemma Institute of Pathobiology, Addis Ababa University. For each test and control tube, batches of 25 female An. stephensi were used to test each insecticide used in IRS. Additionally, cone bioassay tests were conducted to expose An. stephensi from the reared population to four brands of LLINs, MAGNet™ (alpha-cypermethrin), PermaNet^® 2.0 (deltamethrin), DuraNet^© (alpha-cypermethrin) and SafeNet^® (alpha-cypermethrin). A batch of ten sugar-fed female mosquitoes aged 2-5 days was exposed to samples taken from five positions/sides of a net. The data from all replicates were pooled and descriptive statistics were used to describe features of the data.

RESULTS: All An. stephensi collected from Awash Subah Kilo Town and Haro Adi village (around Metehara) were resistant to all tested insecticides used in both IRS and LLINs. Of the tested LLINs, only MAGNet™ (alpha-cypermethrin active ingredient) caused 100% knockdown and mortality to An. stephensi at 60 min and 24 h post exposure, while all other net brands caused mortality below the WHO cut-off points (< 90%). All these nets, except SafeNet^®, were collected during LLIN distribution for community members through the National Malaria Programme, in December 2020.

CONCLUSIONS: Anopheles stephensi is resistant to all tested insecticides used in IRS and in the tested LLIN brands did not cause mosquito mortality as expected, except MAGNet. This suggests that control of this invasive vector using existing adult malaria vector control methods will likely be inadequate and that alternative strategies may be necessary.

PMID:37501142 | DOI:10.1186/s12936-023-04649-5

BMC Public Health. 2023 Jul 27;23(1):1439. doi: 10.1186/s12889-023-16282-7.

ABSTRACT

BACKGROUND: Although evidence on healthcare utilization avoidance during COVID-19 pandemic is emerging, such knowledge is limited in rural settings. An effective policy to the COVID-19 shocks and stresses in rural settings require empirical evidence to inform the design of health policies and programmes. To help overcome this evidence gap and also contribute to policy decisions, this study aimed at examining COVID-19-induced healthcare utilization avoidance and associated factors in rural India.

METHODS: This study used the third-round data from the COVID-19-Related Shocks in Rural India survey conducted between 20-24 September, 2020 across six states. The outcome variable considered in this study was COVID-19-induced healthcare utilization avoidance. Multivariable Binary Logistic Regression Model via Multiple Imputation was used to assess the factors influencing COVID-19-induced healthcare utilization avoidance.

RESULTS: Data on 4,682 respondents were used in the study. Of this, the prevalence of COVID-19-induced healthcare utilization avoidance was 15.5% in rural India across the six states. After adjusting for relevant covariates, participants from the Bihar State have significantly higher likelihood of COVID-19-induced healthcare utilization avoidance compared to those from the Andhra Pradesh. Also, participants whose educational level exceeds high school, those who use government hospital/clinic, engage in daily wage labour in agriculture have significantly higher odds of COVID-19-induced healthcare utilization avoidance compared to their counterparts.

CONCLUSION: Our study revealed that state of residence, type of health facility used, primary work activity and educational level were associated with COVID-19-induced healthcare utilization avoidance in rural India. The findings suggest that policy makers and public health authorities need to formulate policies and design interventions that acknowledge socioeconomic and demographic factors that influence healthcare use avoidance.

PMID:37501140 | DOI:10.1186/s12889-023-16282-7

BMC Med. 2023 Jul 27;21(1):274. doi: 10.1186/s12916-023-02965-w.

ABSTRACT

BACKGROUND: Persistent infection by oncogenic human papillomavirus (HPV) is necessary although not sufficient for development of cervical cancer. Behavioural, environmental, or comorbid exposures may promote or protect against malignant transformation. Randomised evidence is limited and the validity of observational studies describing these associations remains unclear.

METHODS: In this umbrella review, we searched electronic databases to identify meta-analyses of observational studies that evaluated risk or protective factors and the incidence of HPV infection, cervical intra-epithelial neoplasia (CIN), cervical cancer incidence and mortality. Following re-analysis, evidence was classified and graded based on a pre-defined set of statistical criteria. Quality was assessed with AMSTAR-2. For all associations graded as weak evidence or above, with available genetic instruments, we also performed Mendelian randomisation to examine the potential causal effect of modifiable exposures with risk of cervical cancer. The protocol for this study was registered on PROSPERO (CRD42020189995).

RESULTS: We included 171 meta-analyses of different exposure contrasts from 50 studies. Systemic immunosuppression including HIV infection (RR = 2.20 (95% CI = 1.89-2.54)) and immunosuppressive medications for inflammatory bowel disease (RR = 1.33 (95% CI = 1.27-1.39)), as well as an altered vaginal microbiome (RR = 1.59 (95% CI = 1.40-1.81)), were supported by strong and highly suggestive evidence for an association with HPV persistence, CIN or cervical cancer. Smoking, number of sexual partners and young age at first pregnancy were supported by highly suggestive evidence and confirmed by Mendelian randomisation.

CONCLUSIONS: Our main analysis supported the association of systemic (HIV infection, immunosuppressive medications) and local immunosuppression (altered vaginal microbiota) with increased risk for worse HPV and cervical disease outcomes. Mendelian randomisation confirmed the link for genetically predicted lifetime smoking index, and young age at first pregnancy with cervical cancer, highlighting also that observational evidence can hide different inherent biases. This evidence strengthens the need for more frequent HPV screening in people with immunosuppression, further investigation of the vaginal microbiome and access to sexual health services.

PMID:37501128 | DOI:10.1186/s12916-023-02965-w

BMC Geriatr. 2023 Jul 27;23(1):459. doi: 10.1186/s12877-023-04038-2.

ABSTRACT

BACKGROUND: Hip fractures are devastating injuries causing disability, dependence, and institutionalisation, yet hospital care is highly variable. This study aimed to determine hospital organisational factors associated with recovery of mobility and change in patient residence after hip fracture.

METHODS: A cohort of patients aged 60 + years in England and Wales, who sustained a hip fracture from 2016 to 2019 was examined. Patient-level Hospital Episodes Statistics, National Hip Fracture Database, and mortality records were linked to 101 factors derived from 18 hospital-level organisational metrics. After adjustment for patient case-mix, multilevel models were used to identify organisational factors associated with patient residence at discharge, and mobility and residence at 120 days after hip fracture.

RESULTS: Across 172 hospitals, 165,350 patients survived to discharge, of whom 163,230 (99%) had post-hospital discharge destination recorded. 18,323 (11%) died within 120 days. Among 147,027 survivors, 58,344 (40%) across 143 hospitals had their residence recorded, and 56,959 (39%) across 140 hospitals had their mobility recorded, at 120 days. Nineteen organisational factors independently predicted residence on hospital discharge e.g., return to original residence was 31% (95% confidence interval, CI:17-43%) more likely if the anaesthetic lead for hip fracture had time allocated in their job plan, and 8-13% more likely if hip fracture service clinical governance meetings were attended by an orthopaedic surgeon, physiotherapist or anaesthetist. Seven organisational factors independently predicted residence at 120 days. Patients returning to their pre-fracture residence was 26% (95%CI:4-42%) more likely if hospitals had a dedicated hip fracture ward, and 20% (95%CI:8-30%) more likely if treatment plans were proactively discussed with patients and families on admission. Seventeen organisational factors predicted mobility at 120 days. More patients re-attained their pre-fracture mobility in hospitals where (i) care involved an orthogeriatrician (15% [95%CI:1-28%] improvement), (ii) general anaesthesia was usually accompanied by a nerve block (7% [95%CI:1-12%], and (iii) bedside haemoglobin testing was routine in theatre recovery (13% [95%CI:6-20%]).

CONCLUSIONS: Multiple, potentially modifiable, organisational factors are associated with patient outcomes up to 120 days after a hip fracture, these factors if causal should be targeted by service improvement initiatives to reduce variability, improve hospital hip fracture care, and maximise patient independence.

PMID:37501122 | DOI:10.1186/s12877-023-04038-2

J Transl Med. 2023 Jul 27;21(1):506. doi: 10.1186/s12967-023-04374-2.

ABSTRACT

BACKGROUND: The activation of dendritic cells (DCs) is pivotal for generating antigen-specific T-cell responses to eradicate tumor cells. Hence, immunotherapies targeting this interplay are especially intriguing. Moreover, it is of interest to modulate the tumor microenvironment (TME), as this harsh milieu often impairs adaptive immune responses. Oncolytic viral therapy presents an opportunity to overcome the immunosuppression in tumors by destroying tumor cells and thereby releasing antigens and immunostimulatory factors. These effects can be further amplified by the introduction of transgenes expressed by the virus.

METHODS: Lokon oncolytic adenoviruses (LOAd) belong to a platform of chimeric serotype Ad5/35 viruses that have their replication restricted to tumor cells, but the expression of transgenes is permitted in all infected cells. LOAd732 is a novel oncolytic adenovirus that expresses three essential immunostimulatory transgenes: trimerized membrane-bound CD40L, 4-1BBL and IL-2. Transgene expression was determined with flow cytometry and ELISA and the oncolytic function was evaluated with viability assays and xenograft models. The activation profiles of DCs were investigated in co-cultures with tumor cells or in an autologous antigen-specific T cell model by flow cytometry and multiplex proteomic analysis. Statistical differences were analyzed with Kruskal-Wallis test followed by Dunn’s multiple comparison test.

RESULTS: All three transgenes were expressed in infected melanoma cells and DCs and transgene expression did not impair the oncolytic activity in tumor cells. DCs were matured post LOAd732 infection and expressed a multitude of co-stimulatory molecules and pro-inflammatory cytokines crucial for T-cell responses. Furthermore, these DCs were capable of expanding and stimulating antigen-specific T cells in addition to natural killer (NK) cells. Strikingly, the addition of immunosuppressive cytokines TGF-β1 and IL-10 did not affect the ability of LOAd732-matured DCs to expand antigen-specific T cells and these cells retained an enhanced activation profile.

CONCLUSIONS: LOAd732 is a novel immunostimulatory gene therapy based on an oncolytic adenovirus that expresses three transgenes, which are essential for mediating an anti-tumor immune response by activating DCs and stimulating T and NK cells even under imunosuppressive conditions commonly present in the TME. These qualities make LOAd732 an appealing new immunotherapy approach.

PMID:37501121 | DOI:10.1186/s12967-023-04374-2

Acta Neuropathol Commun. 2023 Jul 27;11(1):124. doi: 10.1186/s40478-023-01602-0.

ABSTRACT

To date, several studies on genomic events underlying medulloblastoma (MB) biology have expanded our understanding of this tumour entity and led to its division into four groups-WNT, SHH, group 3 (G3) and group 4 (G4). However, there is little information about the relevance of pathogenic mitochondrial DNA (mtDNA) mutations and their consequences across these. In this report, we describe the case of a female patient with MB and a mitochondriopathy, followed by a study of mtDNA variants in MB groups. After being diagnosed with G4 MB, the index patient was treated in line with the HIT 2000 protocol with no indications of relapse after five years. Long-term side effects of treatment were complemented by additional neurological symptoms and elevated lactate levels ten years later, resulting in suspected mitochondrial disease. This was confirmed by identifying a mutation in the MT-TS1 gene which appeared homoplasmic in patient tissue and heteroplasmic in the patient’s mother. Motivated by this case, we explored mtDNA mutations across 444 patients from ICGC and HIT cohorts. While there was no statistically significant enrichment of mutations in one MB group, both cohorts encompassed a small group of patients harbouring potentially deleterious mtDNA variants. The case presented here highlights the possible similarities between sequelae caused by MB treatment and neurological symptoms of mitochondrial dysfunction, which may apply to patients across all MB groups. In the context of the current advances in characterising and interpreting mtDNA aberrations, recognising affected patients could enhance our future knowledge regarding the mutations’ impact on carcinogenesis and cancer treatment.

PMID:37501103 | DOI:10.1186/s40478-023-01602-0

BMC Res Notes. 2023 Jul 27;16(1):158. doi: 10.1186/s13104-023-06395-y.

ABSTRACT

OBJECTIVE: To examine the clinical efficacy of prophylactic metoclopramide in reducing the incidence of nausea and vomiting in emergency department (ED) patients with acute pain who were treated with intravenous tramadol.

RESULTS: We conducted a single-center randomized, double-blinded, placebo-controlled trial. A total of 99 ED patients presented with acute pain were recruited. Sixty-four patients were randomized, 31 patients in the treatment arm and 33 in the control arm. Overall, there were no significant differences in baseline characteristics between treatment arm and control arm. Only one patient within each arm reported having nausea symptom. No patients reported vomiting episode. There was no statistically significant difference in the proportion of patients with nausea or vomiting symptoms between the two groups (3.2% in the treatment arm vs. 3.0% in the control arm, p = 1.000). The administration of prophylactic metoclopramide may not provide additional benefit in reducing the occurrence of nausea and/or vomiting episode in ED patients with acute pain treated with intravenous tramadol. Trial registration Randomized clinical trial TCTR20220525001; registration date: 21 October 2021. Retrospectively registered.

PMID:37501098 | DOI:10.1186/s13104-023-06395-y

Chaos. 2023 Jul 1;33(7):073151. doi: 10.1063/5.0159675.

ABSTRACT

Dynamical systems that are used to model power grids, the brain, and other physical systems can exhibit coexisting stable states known as attractors. A powerful tool to understand such systems, as well as to better predict when they may “tip” from one stable state to the other, is global stability analysis. It involves identifying the initial conditions that converge to each attractor, known as the basins of attraction, measuring the relative volume of these basins in state space, and quantifying how these fractions change as a system parameter evolves. By improving existing approaches, we present a comprehensive framework that allows for global stability analysis of dynamical systems. Notably, our framework enables the analysis to be made efficiently and conveniently over a parameter range. As such, it becomes an essential tool for stability analysis of dynamical systems that goes beyond local stability analysis offered by alternative frameworks. We demonstrate the effectiveness of our approach on a variety of models, including climate, power grids, ecosystems, and more. Our framework is available as simple-to-use open-source code as part of the DynamicalSystems.jl library.

PMID:37499248 | DOI:10.1063/5.0159675

JCO Oncol Pract. 2023 Jul 27:OP2300146. doi: 10.1200/OP.23.00146. Online ahead of print.

ABSTRACT

PURPOSE: Burkitt lymphoma is an aggressive B-cell lymphoma requiring intensive therapy, which places patients at risk for severe toxicity. However, few studies have described these patients’ clinical outcomes and health care utilization, particularly among older adults.

METHODS: We conducted a retrospective analysis of adults 40 years and older with Burkitt lymphoma at Massachusetts General Hospital and Dana-Farber Cancer Institute from February 1999 to December 2020 (N = 97). We abstracted patient characteristics, clinical outcomes, and health care utilization (unplanned hospitalizations, intensive care unit [ICU] admissions) during therapy from the electronic health record. Using univariate logistic regression, we examined factors associated with rates of unplanned hospitalization and ICU admission during therapy.

RESULTS: Among evaluable patients (median age, 69 years; 23.7% female; 19.3% with bone marrow involvement), 45.8% (38 of 83) experienced unplanned hospitalization and 23.2% (19 of 82) experienced ICU admission during therapy. Among those 70 years and older, rates of unplanned hospitalization and ICU admission were 36.8% (14 of 38) and 29.0% (11 of 38), respectively. Bone marrow involvement (odds ratio [OR], 3.00; P = .069) was associated with a nonsignificantly greater likelihood of unplanned hospitalization. Older age (OR, 1.06; P = .039), Charlson comorbidity index >0 (OR, 3.14; P = .038), and hypoalbuminemia (OR, 3.22; P = .035) were associated with greater likelihood of ICU admission. Overall, 8.7% (8 of 92) of patients died during treatment, all of whom were 70 years and older.

CONCLUSION: Adults with Burkitt lymphoma experience substantial rates of unplanned hospitalizations and ICU admissions, with older adults at especially high risk for ICU admission and death during treatment. Our findings underscore the need to develop supportive care interventions for patients with Burkitt lymphoma to help improve clinical outcomes and health care utilization.

PMID:37499211 | DOI:10.1200/OP.23.00146