Nevin Manimala

SAR QSAR Environ Res. 2023 Jul-Sep;34(8):639-659. doi: 10.1080/1062936X.2023.2247326.

ABSTRACT

2,4-Disubstituted quinoline derivatives were designed based on a 3D-QSAR study, synthesized and evaluated for antimalarial activity. A large dataset of 178 quinoline derivatives was used to perform a 3D-QSAR study using CoMFA and CoMSIA models. PLS analysis provided statistically validated results for CoMFA (r²_ncv = 0.969, q² = 0.677, r²_cv = 0.682) and CoMSIA (r²_ncv = 0.962, q² = 0.741, r²_cv = 0.683) models. Two series of a total of 40 2,4-disubstituted quinoline derivatives were designed with amide (quinoline-4-carboxamide) and secondary amine (4-aminoquinoline) linkers at the -C4 position of the quinoline ring. For the purpose of selecting better compounds for synthesis with good pEC₅₀ values, activity prediction was carried out using CoMFA and CoMSIA models. Finally, a total of 10 2,4-disubstituted quinoline derivatives were synthesized, and screened for their antimalarial activity based on the reduction of parasitaemia. Compound #5 with amide linker and compound #19 with secondary amine linkers at the -C4 position of the quinoline ring showed maximum reductions of 64% and 57%, respectively, in the level of parasitaemia. In vivo screening assay confirmed and validated the findings of the 3D-QSAR study for the design of quinoline derivatives.

PMID:37651746 | DOI:10.1080/1062936X.2023.2247326

Retina. 2023 Aug 29. doi: 10.1097/IAE.0000000000003918. Online ahead of print.

ABSTRACT

PURPOSE: To determine the utility of Ultra-widefield (UWF) imaging in detecting pathologic peripheral retinal tears and holes.

METHODS: This was a retrospective, observational study. One-hundred and ninety-eight eyes of 198 patients diagnosed with acute posterior vitreous detachment were included. Eyes were divided into two groups: 89 eyes with peripheral retinal holes and tears treated with laser retinopexy (treatment group) and 109 control eyes. Patients underwent UWF imaging and indirect ophthalmoscopy with scleral depression. UWF images from both groups were reviewed by two blinded graders and then compared to funduscopic exam and medical records.

RESULTS: UWF imaging identified 60 of the 89 eyes (sensitivity of 67.4%) found to have treatment-requiring peripheral retinal lesions and 107 of the 109 control eyes (specificity of 98.2%).The distribution of misses based on octant location did reach statistical significance (p=0.004). Lesions anterior to the equator were more likely to be missed (21/41 eyes, 51.2%) compared to those located posterior to the equator (4/20 eyes, 25.0%) and at the equator (4/28, 14.3%), p=0.002. The combined discordance rate between graders in the entire cohort was 12.1% (24/198 eyes) yielding an inter-rater agreement of 87.9%.

CONCLUSIONS: UWF imaging showed a moderate sensitivity and high specificity in detecting treatment requiring retinal tears and holes, with high inter-rater agreement. Given there is only a moderate sensitivity in identifying treatment requiring retinal tears and holes, UWF imaging can assist with clinical exam, but a 360-degree scleral depressed exam should remain the gold standard.

PMID:37651732 | DOI:10.1097/IAE.0000000000003918

Eur J Prev Cardiol. 2023 Aug 31:zwad267. doi: 10.1093/eurjpc/zwad267. Online ahead of print.

ABSTRACT

AIMS: Isolated sinus node dysfunction (ISND) is a sinus node dysfunction without atrial fibrillation. A high risk of ischaemic stroke (IS) has been reported in ISND populations. However, current guidelines do not recommend anticoagulation in ISND management. P-wave indicates ISND-related atrial remodelling. P-wave indices and the CHA2DS2-VASc score may contribute to risk stratification for ISND-related IS.

METHODS AND RESULTS: In this multi-centre longitudinal cohort, ISND patients were divided into development (n = 1185) and external validation (n = 988) cohorts. Ischaemic stroke prediction capacity of the P-combined score was assessed with regard to discrimination, calibration, and clinical effectiveness. The cut-off value of the score was confirmed by using a restricted cubic spline curve. One hundred and twenty-four (10.46%) ISND patients developed IS [1.63%/year; 95% confidence interval (CI): 1.49-1.78%/year] after a median 3.02-year follow-up in the development cohort. The P-wave terminal force in electrocardiogram-lead V1 (PTFV1) was the only significantly abnormal P-wave index (adjusted hazard ratio: 2.56; 95% CI: 1.72-3.80). Therefore, we incorporated the PTFV1 with the CHA2DS2-VASc score to generate a P-combined score. For a 5-year IS risk, the P-combined score improved Harrell’s C-statistic (95% CI) from 0.678 (0.618-0.738) to 0.716 (0.657-0.774) and 0.747 (0.677-0.816) to 0.808 (0.747-0.868) in the development and validation cohorts, respectively, along with calibration and decision curve analyses. The cut-off value of the score was 3 in the development cohort and well-discriminated in the validation cohort.

CONCLUSION: Chinese ISND patients have a higher IS risk than the general population. Compared with the CHA2DS2-VASc score, the PTFV1-combined CHA2DS2-VASc score shows a better risk-stratification capacity for ISND-related IS.

PMID:37651722 | DOI:10.1093/eurjpc/zwad267

Am J Hosp Palliat Care. 2023 Aug 31:10499091231199722. doi: 10.1177/10499091231199722. Online ahead of print.

ABSTRACT

Introduction: The hospice-in-place program at Vanderbilt University Medical Center (VUMC) is available to patients and families who elect for hospice benefits and are too unstable to be transported for hospice care. The goal of this study was to assess the satisfaction of family members of patients who died while hospitalized at VUMC and received hospice-in-place compared to the families of patients who did not receive hospice care. Methods: Next-of-kin satisfaction was measured through the administration of qualitative interviews and quantitative questionnaires. Semi-structured interviews were audio-recorded, and transcripts were analyzed using an iterative inductive-deductive approach to develop a conceptual framework. Participants were also asked to respond to a 10-question satisfaction questionnaire. Results: Forty participants were enrolled: 20 next-of-kin of patients who received hospice-in-place and 20 next-of-kin of patients who passed without hospice. Factors influencing satisfaction were organized into a conceptual framework with three categories: individual-level factors, systems-level factors, and modifying factors. For the questionnaires, the hospice-in-place group had a mean satisfaction score of 4.54 (0.76) out of five, while the non-hospice group had a mean score of 4.14 (1.00). A comparison of the two groups’ responses did not show a statistically significant difference (P = 0.06). Discussion: Quantitative findings of this study showed improved satisfaction but were unable to show a significant difference in satisfaction with hospice-in-place compared to traditional care. Questionnaire results suggest that both types of care yield high satisfaction scores and are successfully supporting patients and families. The conceptual framework also adds to the understanding of end-of-life experiences at VUMC.

PMID:37651687 | DOI:10.1177/10499091231199722

Am J Hematol. 2023 Aug 31. doi: 10.1002/ajh.27059. Online ahead of print.

ABSTRACT

Low hemoglobin is widely used as an indicator of iron deficiency anemia in India and other low-and-middle income counties, but anemia need not accurately reflect iron deficiency. We examined the relationship between hemoglobin and biomarkers of iron status in antenatal and postnatal period. Secondary analysis of uncomplicated singleton pregnancies in two Indian study cohorts: 1132 antenatal women in third trimester and 837 postnatal women 12-72 h after childbirth. Associations of hemoglobin with ferritin in both data sets, and with sTfR, TSAT, and hepcidin in the postnatal cohort were examined using multivariable linear regression. Multinomial logistic regression was used to examine the association between severity of anemia and iron status. Regression models were adjusted for potential confounders. Over 55% of the women were anemic; 34% of antenatal and 40% of postnatal women had low ferritin, but 4% antenatal and 6% postnatal women had high ferritin. No evidence of association between hemoglobin and ferritin was observed (antenatal: adjusted coefficient [aCoef] -0.0004, 95% confidence interval [CI] -0.001, 0.001; postnatal: aCoef -0.0001, 95% CI -0.001, 0.001). We found a significant linear association of hemoglobin with sTfR (aCoef -0.04, 95% CI -0.07, -0.01), TSAT (aCoef -0.005, 95% CI -0.008, -0.002), and hepcidin (aCoef 0.02, 95% CI 0.02, 0.03) in postnatal women. Likelihood of low ferritin was more common in anemic than non-anemic women, but high ferritin was also more common in women with severe anemia in both cohorts. Causes of anemia in pregnant and postpartum women in India are multifactorial; low hemoglobin alone is not be a useful marker of iron deficiency.

PMID:37651649 | DOI:10.1002/ajh.27059

J Glob Health. 2023 Sep 1;13:04085. doi: 10.7189/jogh.13.04085.

ABSTRACT

BACKGROUND: Strabismus is a misalignment of the visual axis that affects 2-3% of the population and can lead to loss of binocular vision. It is currently controversial whether there is a gender difference in the most common form of visual misalignment: horizontal strabismus. Some studies claimed that more females than males have an outward deviation (exotropia), while others concluded that there is no significant gender difference. No previous work has systematically explored gender differences in horizontal strabismus or has compared the results of population-based studies with those of clinic-based studies.

METHODS: We conducted a systematic review and meta-analysis of studies reporting the prevalence of horizontal strabismus. We included 73 population-based studies and compared their disclosed gender population with that in 141 comparable clinical-based studies. We analysed the data according to gender, strabismus type (esotropia, exotropia), and geographic region/ethnicity.

RESULTS: Summary statistics showed a nearly identical prevalence of horizontal strabismus (2.558% for males, 2.582% for females), esotropia (1.386% males vs. 1.377% females), and of exotropia (1.035% males vs. 1.043% females). Meta-analysis results showed that these differences between males and females were not statistically significant (odds ratio (OR) = 1.01; 95% confidence interval (CI) = 0.97-1.10), but that females were significantly more frequent (by 7.50%) in clinic-based studies than males, with 5.00% more females for esotropia, and 12.20% more females for exotropia when adjusted for the population’s sex ratio. The extent of the female gender bias differed between geographic regions/societies, with Asians having the lowest bias towards females and Latin American countries having the strongest bias.

CONCLUSIONS: Males and females have the same prevalence of horizontal strabismus, including exotropia. Females with strabismus seek health care or are brought to clinics significantly more often than males. This is an example of gender bias in health care in favour of females rather than males, apparently because parents – erroneously fearing only cosmetic consequences – are more concerned about strabismus in their daughters than their sons. Societal attitudes towards females, as well as economic factors (insurance status), appear to be relevant factors that determine the magnitude of the gender bias in horizontal strabismus.

PMID:37651634 | DOI:10.7189/jogh.13.04085

Brief Funct Genomics. 2023 Aug 31:elad039. doi: 10.1093/bfgp/elad039. Online ahead of print.

ABSTRACT

DNA-binding proteins (DBPs) play critical roles in many biological processes, including gene expression, DNA replication, recombination and repair. Understanding the molecular mechanisms underlying these processes depends on the precise identification of DBPs. In recent times, several computational methods have been developed to identify DBPs. However, because of the generic nature of the models, these models are unable to identify species-specific DBPs with higher accuracy. Therefore, a species-specific computational model is needed to predict species-specific DBPs. In this paper, we introduce the computational DBPMod method, which makes use of a machine learning approach to identify species-specific DBPs. For prediction, both shallow learning algorithms and deep learning models were used, with shallow learning models achieving higher accuracy. Additionally, the evolutionary features outperformed sequence-derived features in terms of accuracy. Five model organisms, including Caenorhabditis elegans, Drosophila melanogaster, Escherichia coli, Homo sapiens and Mus musculus, were used to assess the performance of DBPMod. Five-fold cross-validation and independent test set analyses were used to evaluate the prediction accuracy in terms of area under receiver operating characteristic curve (auROC) and area under precision-recall curve (auPRC), which was found to be ~89-92% and ~89-95%, respectively. The comparative results demonstrate that the DBPMod outperforms 12 current state-of-the-art computational approaches in identifying the DBPs for all five model organisms. We further developed the web server of DBPMod to make it easier for researchers to detect DBPs and is publicly available at https://iasri-sg.icar.gov.in/dbpmod/. DBPMod is expected to be an invaluable tool for discovering DBPs, supplementing the current experimental and computational methods.

PMID:37651627 | DOI:10.1093/bfgp/elad039

Physiother Theory Pract. 2023 Aug 31:1-8. doi: 10.1080/09593985.2023.2253313. Online ahead of print.

ABSTRACT

BACKGROUND: Poststroke shoulder pain (PSSP) is a common poststroke complication. Even though it is a common phenomenon, it is unclear how it impacts the patient’s life.

OBJECTIVE: To investigate the differences in upper extremity function, sleep quality, and functional independence between patients with and without PSSP.

METHODS: This cross-sectional study included 63 participants with stroke (32 patients with PSSP and 31 patients without PSSP). Shoulder pain was evaluated with a Visual Analog Scale and the participants were divided into two groups as those with and without PSSP. The upper extremity function was assessed with the Disabilities of the Arm, Shoulder, and Hand Questionnaire, the Arm Motor Ability Test, and the Nine Hole Peg Test. Sleep quality was assessed with Pittsburgh Sleep Quality Index and the functional independence was assessed with the Functional Independence Measure. All data were analyzed using the program IBM SPSS Statistics 22.0. The Mann-Whitney U test was used to compare the non-normally distributed parameters, and the Chi-square test was used to compare the ordinal variables. The Spearman correlation test was used for the relationship and a linear regression test was used for regression.

RESULTS: Upper extremity function decreased (p < .05), only the sleep disturbance sub-parameter of sleep quality increased (p = .01), and functional independence increased in patients with PSSP (p < .001). There was a moderate relationship between pain and upper extremity function and a fair relationship between pain and sleep quality (use of sleep medications, daytime dysfunction sub-parameters) (p < .05).

CONCLUSIONS: PSSP impairs upper extremity functions, which play an important role in activities of daily living, and reduces functional independence. These results suggest that it is important to evaluate shoulder pain and examine the factors affecting pain in the rehabilitation of patients with stroke.

PMID:37651602 | DOI:10.1080/09593985.2023.2253313

Clin Spine Surg. 2023 Aug 22. doi: 10.1097/BSD.0000000000001512. Online ahead of print.

ABSTRACT

STUDY DESIGN: A retrospective cohort.

OBJECTIVE: We utilize big data and modeling techniques to create optimized comorbidity indices for predicting postoperative outcomes following cervical spine fusion surgery.

SUMMARY OF BACKGROUND DATA: Cervical spine decompression and fusion surgery are commonly used to treat degenerative cervical spine pathologies. However, there is a paucity of high-quality data defining the optimal comorbidity indices specifically in patients undergoing cervical spine fusion surgery.

METHODS: Using data from 2016 to 2019, we queried the Nationwide Readmissions Database (NRD) to identify individuals who had received cervical spine fusion surgery. The Johns Hopkins Adjusted Clinical Groups (JHACG) frailty-defining indicator was used to assess frailty. To measure the level of comorbidity, Elixhauser Comorbidity Index (ECI) scores were queried. Receiver operating characteristic curves were developed utilizing comorbidity indices as predictor variables for pertinent complications such as mortality, nonroutine discharge, top-quartile cost, top-quartile length of stay, and 1-year readmission.

RESULTS: A total of 453,717 patients were eligible. Nonroutine discharges occurred in 93,961 (20.7%) patients. The mean adjusted all-payer cost for the procedure was $22,573.14±18,274.86 (top quartile: $26,775.80) and the mean length of stay was 2.7±4.4 days (top quartile: 4.7 d). There were 703 (0.15%) mortalities and 58,254 (12.8%) readmissions within 1 year postoperatively. Models using frailty+ECI as primary predictors consistently outperformed the ECI-only model with statistically significant P-values for most of the complications assessed. Cost and mortality were the only outcomes for which this was not the case, as frailty outperformed both ECI and frailty+ECI in cost (P<0.0001 for all) and frailty+ECI performed as well as ECI alone in mortality (P=0.10).

CONCLUSIONS: Our data suggest that frailty+ECI may most accurately predict clinical outcomes in patients receiving cervical spine fusion surgery. These models may be used to identify high-risk populations and patients who may necessitate greater resource utilization following elective cervical spinal fusion.

PMID:37651572 | DOI:10.1097/BSD.0000000000001512

Ther Drug Monit. 2023 Aug 24. doi: 10.1097/FTD.0000000000001137. Online ahead of print.

NO ABSTRACT

PMID:37651569 | DOI:10.1097/FTD.0000000000001137