Category: Nevin Manimala

BMC Microbiol. 2023 Dec 12;23(1):396. doi: 10.1186/s12866-023-03094-3.

ABSTRACT

Malaria is a persistent illness that is still a public health issue. On the other hand, marine organisms are considered a rich source of anti‑infective drugs and other medically significant compounds. Herein, we reported the isolation of the actinomycete associated with the Red Sea sponge Callyspongia siphonella. Using “one strain many compounds” (OSMAC) approach, a suitable strain was identified and then sub-cultured in three different media (M1, ISP2 and OLIGO). The extracts were evaluated for their in-vitro antimalarial activity against Plasmodium falciparum strain and subsequently analyzed by Liquid chromatography coupled with high-resolution mass spectrometry (LC-HR-MS). In addition, MetaboAnalyst 5.0 was used to statistically analyze the LC-MS data. Finally, Molecular docking was carried out for the dereplicated metabolites against lysyl-tRNA synthetase (PfKRS1). The phylogenetic study of the 16S rRNA sequence of the actinomycete isolate revealed its affiliation to Streptomyces genus. Antimalarial screening revealed that ISP2 media is the most active against Plasmodium falciparum strain. Based on LC-HR-MS based metabolomics and multivariate analyses, the static cultures of the media, ISP2 (ISP2-S) and M1 (M1-S), are the optimal media for metabolites production. OPLS-DA suggested that quinone derivatives are abundant in the extracts with the highest antimalarial activity. Fifteen compounds were identified where eight of these metabolites were correlated to the observed antimalarial activity of the active extracts. According to molecular docking experiments, saframycin Y3 and juglomycin E showed the greatest binding energy scores (-6.2 and -5.13) to lysyl-tRNA synthetase (PfKRS1), respectively. Using metabolomics and molecular docking investigation, the quinones, saframycin Y3 (5) and juglomycin E (1) were identified as promising antimalarial therapeutic candidates. Our approach can be used as a first evaluation stage in natural product drug development, facilitating the separation of chosen metabolites, particularly biologically active ones.

PMID:38087203 | DOI:10.1186/s12866-023-03094-3

BMC Palliat Care. 2023 Dec 12;22(1):198. doi: 10.1186/s12904-023-01317-y.

ABSTRACT

OBJECTIVE: The aims of the study were first to explore the adaptive leisure activities of classified nursing model from the perspective of nurse-patient interactive care, and to explore its impact on the physical and mental health of patients with colon cancer.

METHODS: From September 2017 to March 2022 as the observation time node, 82 patients with colon cancer who met the established inclusion and exclusion criteria were regarded as the research objects through the random number table as the grouping tool. The two groups of patients were named as the research group and the control group, with 41 patients in each group. The control group implemented routine nursing measures, and the research group implemented classified nursing mode and adaptive leisure activity mode. The two groups of patients received 4 weeks of nursing intervention. With the help of self-rating anxiety scale, self-rating depression scale, self-care ability evaluation scale and health status survey brief form, the two groups of patients were compared before intervention and at the end of the 4th week after intervention.

RESULTS: After the intervention, the anxiety score (t = 6.656, p < 0.001) and depression score (t = 4.851, p < 0.001) of the research group were lower than those of the control group, and the difference was statistically significant. After the intervention, the self-concept (t = 4.845, p < 0.001), self-responsibility (t = 6.071, p < 0.001), self-care skills (t = 3.341, p < 0.001), health knowledge (t = 3.698, p < 0.001) and total score (t = 9.246, p < 0.001) of the research group were higher than those of the control group, and the difference was statistically significant. After the intervention, physical functioning (t = 8.141, p < 0.001), bodily pain (t = 6.083, p < 0.001), general health (t = 9.424, p < 0.001), role-physical (t = 8.057, p < 0.001), role-emotional (t = 13.252, p < 0.001), mental health (t = 12.565, p < 0.001), social functioning (t = 10.813, p < 0.001) and vitality score (t = 12.890, p < 0.001) of the research group were higher than those of the control group, with significant differences.

CONCLUSION: Interactive care through adaptive leisure nursing improves mental well-being, self-management, and psychosocial functioning in elderly colon cancer patients, promoting overall health.

PMID:38087201 | DOI:10.1186/s12904-023-01317-y

J Gen Intern Med. 2023 Dec 12. doi: 10.1007/s11606-023-08415-w. Online ahead of print.

ABSTRACT

BACKGROUND: We define a “flagship hospital” as the largest academic hospital within a hospital referral region and a “flagship system” as a system that contains a flagship hospital and its affiliates. It is not known if patients admitted to an affiliate hospital, and not to its main flagship hospital, have better outcomes than those admitted to a hospital outside the flagship system but within the same hospital referral region.

OBJECTIVE: To compare mortality at flagship hospitals and their affiliates to matched control patients not in the flagship system but within the same hospital referral region.

DESIGN: A matched cohort study PARTICIPANTS: The study used hospitalizations for common medical conditions between 2018-2019 among older patients age ≥ 66 years. We analyzed 118,321 matched pairs of Medicare patients admitted with pneumonia (N=57,775), heart failure (N=42,531), or acute myocardial infarction (N=18,015) in 35 flagship hospitals, 124 affiliates, and 793 control hospitals.

MAIN MEASURES: 30-day (primary) and 90-day (secondary) all-cause mortality.

KEY RESULTS: 30-day mortality was lower among patients in flagship systems versus control hospitals that are not part of the flagship system but within the same hospital referral region (difference= -0.62%, 95% CI [-0.88%, -0.37%], P<0.001). This difference was smaller in affiliates versus controls (-0.43%, [-0.75%, -0.11%], P=0.008) than in flagship hospitals versus controls (-1.02%, [-1.46%, -0.58%], P<0.001; difference-in-difference -0.59%, [-1.13%, -0.05%], P=0.033). Similar results were found for 90-day mortality.

LIMITATIONS: The study used claims-based data.

CONCLUSIONS: In aggregate, within a hospital referral region, patients treated at the flagship hospital, at affiliates of the flagship hospital, and in the flagship system as a whole, all had lower mortality rates than matched controls outside the flagship system. However, the mortality advantage was larger for flagship hospitals than for their affiliates.

PMID:38087179 | DOI:10.1007/s11606-023-08415-w

AIDS Behav. 2023 Dec 13. doi: 10.1007/s10461-023-04220-y. Online ahead of print.

ABSTRACT

Improvement in treatment options has increased the survival of people living with HIV (PLHIV). Thus, we evaluated the factors associated with better health-related quality of life (HRQoL) among PLHIV in Brazil. This was a cross-sectional study carried out among 349 PLHIV. Data were collected using an interview-based questionnaire, and HRQoL was assessed by the Brazilian version of the WHOQOL HIV BREF instrument. We used non-hierarchical cluster analysis (K-means) to compile the WHOQOL HIV BREF’s overall and domain scores into a unique more multidimensional measure for HRQoL consisting of three clusters: poor, fair and good; associations with clusters of better HRQoL were assessed using multinomial logistic regression models. The mean and median overall HRQoL scores were 15.13 (SD = 3.39) and 16, respectively. The reliability and validity of the Brazilian version of the WHOQOL HIV BREF instrument was confirmed among PLHIV in a non-metropolitan, medium-sized municipality of Brazil, which reaffirmed the cross-cultural validity of this instrument. The factors male sex; heterosexual and asexual orientations; higher individual income; undetectable viral load; absence of any comorbidity and presence of an infectious or a chronic comorbidity, with mental illness as the reference; and never having consumed illegal substances were independently associated with good HRQoL. Thus, the compilation of the WHOQOL HIV BREF’s overall and domain scores into a unique multidimensional measure for HRQoL, which this study proposed for the first time, may facilitate more robust interpretations and models of predictors. These differentials could simplify HRQoL as an indicator of health and wellbeing to be routinely used as a key outcome in the clinical management of patients and in the global monitoring of health system responses to HIV.

PMID:38087154 | DOI:10.1007/s10461-023-04220-y

Brain Imaging Behav. 2023 Dec 12. doi: 10.1007/s11682-023-00835-w. Online ahead of print.

ABSTRACT

To comprehensively investigate the potential temporal dynamic and static abnormalities of spontaneous brain activity (SBA) in left temporal lobe epilepsy (LTLE) and right temporal lobe epilepsy (RTLE) and to detect whether these alterations correlate with cognition. Twelve SBA metrics, including ALFF, dALFF, fALFF, dfALFF, ReHo, dReHo, DC, dDC, GSCorr, dGSCorr, VMHC, and dVMHC, in 46 LTLE patients, 43 RTLE patients, and 53 healthy volunteers were compared in the voxel-wise analysis. Correlation analyses between metrics in regions showing statistic differences and epilepsy duration, epilepsy severity, and cognition scores were also performed. Compared with the healthy volunteers, the alteration of SBA was identified both in LTLE and RTLE patients. The ALFF, fALFF, and dALFF values in LTLE, as well as the fALFF values in RTLE, increased in the bilateral thalamus, basal ganglia, mesial temporal lobe, cerebellum, and vermis. Increased dfALFF in the bilateral basal ganglia, increased ReHo and dReHo in the bilateral thalamus in the LTLE group, increased ALFF and dALFF in the pons, and increased ReHo and dReHo in the right hippocampus in the RTLE group were also detected. However, the majority of deactivation clusters were in the ipsilateral lateral temporal lobe. For LTLE, the fALFF, DC, dDC, and GSCorr values in the left lateral temporal lobe and the ReHo and VMHC values in the bilateral lateral temporal lobe all decreased. For RTLE, the ALFF, fALFF, dfALFF, ReHo, dReHo, and DC values in the right lateral temporal lobe and the VMHC values in the bilateral lateral temporal lobe all decreased. Moreover, for both the LTLE and RTLE groups, the dVMHC values decreased in the calcarine cortex. The most significant difference between LTLE and RTLE was the higher activation in the cerebellum of the LTLE group. The alterations of many SBA metrics were correlated with cognition and epilepsy duration. The patterns of change in SBA abnormalities in the LTLE and RTLE patients were generally similar. The integrated application of temporal dynamic and static SBA metrics might aid in the investigation of the propagation and suppression pathways of seizure activity as well as the cognitive impairment mechanisms in TLE.

PMID:38087148 | DOI:10.1007/s11682-023-00835-w

Parasitol Res. 2023 Dec 13;123(1):33. doi: 10.1007/s00436-023-08040-w.

ABSTRACT

Fasciolosis is a zoonosis that limits the productivity of ruminants worldwide, but there is a lack of information on its occurrence in Burundi. Therefore, this study aimed to fill the information gap by determining the prevalence and risk factors associated with bovine fasciolosis in the Imbo Region of Burundi. Two prevalence studies were conducted in parallel in the five communes of the five provinces in the Imbo region. In the first study, a total of 426 fecal samples were collected from randomly selected cattle farms and microscopically examined to determine Fasciola egg burden. Survey data on cattle husbandry were collected from owners of these cattle and analyzed to determine the risk factors for bovine fasciolosis. In the second study, 467 cattle were randomly selected in abattoirs and their livers were examined postmortem to determine liver fluke burdens. Data were entered separately into Microsoft Excel and analyzed using R software. The overall prevalence of bovine fasciolosis was 47.7% (42.9-52.4, 95% CI) for microscopic examination and 33.2% (28.9-37.5, 95% CI) for postmortem examinations. The majority of positive cattle (60.6%) had light intensity infections as determined by eggs per gram of feces (epg). Postmortem examinations corroborated these results and indicated that 80% of cattle had light intensity infections. Chi-square analysis showed a statistical association with the presence of bovine fasciolosis and the age, sex, and origin of cattle and the practices of cattle owners (P < 0.05).

PMID:38087118 | DOI:10.1007/s00436-023-08040-w

Nat Med. 2023 Dec 12. doi: 10.1038/s41591-023-02601-3. Online ahead of print.

ABSTRACT

To support a strategy to eliminate cervical cancer as a public health problem, the World Health Organisation (WHO) reviewed its guidelines for screening and treatment of cervical pre-cancerous lesions in 2021. Women living with HIV have 6-times the risk of cervical cancer compared to women in the general population, and we harnessed a model platform (‘Policy1-Cervix-HIV’) to evaluate the benefits and harms of a range of screening strategies for women living with HIV in Tanzania, a country with endemic HIV. Assuming 70% coverage, we found that 3-yearly primary HPV screening without triage would reduce age-standardised cervical cancer mortality rates by 72%, with a number needed to treat (NNT) of 38.7, to prevent a cervical cancer death. Triaging HPV positive women before treatment resulted in minimal loss of effectiveness and had more favorable NNTs (19.7-33.0). Screening using visual inspection with acetic acid (VIA) or cytology was less effective than primary HPV and, in the case of VIA, generated a far higher NNT of 107.5. These findings support the WHO 2021 recommendation that women living with HIV are screened with primary HPV testing in a screen-triage-and-treat approach starting at 25 years, with regular screening every 3-5 years.

PMID:38087116 | DOI:10.1038/s41591-023-02601-3

J Prev (2022). 2023 Dec 12. doi: 10.1007/s10935-023-00756-w. Online ahead of print.

ABSTRACT

Predictors of hypertension (HTN) control status have not been well understood in India. This information is crucial for policymakers and program managers to devise newer HTN control strategies and implement relevant policies and programs. Therefore, we undertook this meta-analysis to estimate the effect of various factors on the control status of HTN in India. We systematically searched PubMed and Embase for observational studies and community-based trials published between April 2013 and March 2021 conducted among people (≥ 15 years) with hypertension in India. Quality of studies was assessed using Newcastle Ottawa (NO) scale. Meta-analysis was performed using random effects model. We reported the effect of various factors on the prevalence of controlled HTN using pooled odds ratio (OR) with 95% confidence interval (CI). Of the 842 studies screened, we analyzed nine studies that included 2,441 individuals. Based on the NO scale, majority (90%) of studies had a low risk of bias. The odds of having controlled HTN were significantly higher among women (OR 1.78, 95% CI 1.62-1.95), those aged > 45 years (OR 1.69, 95% CI 1.44-1.97), and those residing in urban parts of India (OR 1.74; 95% CI 1.48-2.03). These measures varied considerably across different regions of the country. Very few studies reported data on the relationship between behavioural risk factors of non-communicable diseases (NCDs) and HTN control status. We did not find any statistically significant differences between behavioural risk factors of NCDs and HTN control status. To improve HTN control in India, the ongoing/newer HTN control programs need to target men, those aged 15-45, and rural residents. Future studies on HTN control determinants should report disaggregated data and use standardized definitions for behavioral risk factors to enhance reliability and comprehensiveness of findings on the determinants of HTN control in future reviews.

PMID:38087106 | DOI:10.1007/s10935-023-00756-w

Nat Struct Mol Biol. 2023 Dec;30(12):1947-1957. doi: 10.1038/s41594-023-01161-x. Epub 2023 Dec 12.

ABSTRACT

JTE-607 is an anticancer and anti-inflammatory compound and its active form, compound 2, directly binds to and inhibits CPSF73, the endonuclease for the cleavage step in pre-messenger RNA (pre-mRNA) 3′ processing. Surprisingly, compound 2-mediated inhibition of pre-mRNA cleavage is sequence specific and the drug sensitivity is predominantly determined by sequences flanking the cleavage site (CS). Using massively parallel in vitro assays, we identified key sequence features that determine drug sensitivity. We trained a machine learning model that can predict poly(A) site (PAS) relative sensitivity to compound 2 and provide the molecular basis for understanding the impact of JTE-607 on PAS selection and transcription termination genome wide. We propose that CPSF73 and associated factors bind to the CS region in a sequence-dependent manner and the interaction affinity determines compound 2 sensitivity. These results have not only elucidated the mechanism of action of JTE-607, but also unveiled an evolutionarily conserved sequence specificity of the mRNA 3′ processing machinery.

PMID:38087090 | DOI:10.1038/s41594-023-01161-x

J Cancer Educ. 2023 Dec 12. doi: 10.1007/s13187-023-02390-w. Online ahead of print.

ABSTRACT

There is a paucity of formalized exposure to Radiation Oncology (RO) for preclinical medical students across the United States as well as barriers to implementation within undergraduate medical education curriculum at many institutions. We present a novel approach to implementing an introductory RO didactic lecture to second-year medical students by interweaving associated oncological and ionizing radiation content represented on the United States Medical Licensing Exam® (USMLE®) Step 1 examination. Students had synchronous and asynchronous opportunities to engage with the 1.0-h didactic lecture administered by an attending Radiation Oncologist faculty member. Students were electronically invited to anonymously rank the effectiveness of the lecture materials on a 5-point Likert scale. Performance on standardized board-style questions regarding radiation biology and radiation side effects was recorded before and after the lecture and compared to the historic performance of previous institutional second-year medical student cohorts. The lecture material effectiveness received a mean score of 4.50 on a 5-point Likert scale. There was a statistically significant improvement in student performance on a board-style radiation side effect question from 39% on a pretest to 76% on a posttest. A USMLE® topic-based approach may be an effective way to implement a formalized introduction to RO to preclinical medical students while simultaneously improving performance on relevant standardized board-style questions. Providing evidence that RO topics appear on the USMLE® Step 1 examination curriculum was a powerful incentive for implementation when negotiating with curriculum offices.

PMID:38087075 | DOI:10.1007/s13187-023-02390-w