Nevin Manimala

J Biomol Struct Dyn. 2022 Mar 23:1-18. doi: 10.1080/07391102.2022.2051745. Online ahead of print.

ABSTRACT

Hypoxia-inducible factor (HIF) is a transcriptional factor which plays a crucial role in tumour metastasis thereby responsible for development of various forms of cancers. Indazole derivatives have been reported in the literature as potent HIF-1α inhibitor via interaction with key residues of the HIF-1α active site. Taking into consideration the role HIF-1α in cancer and potency of indazole derivative against HIF-1α; it was considered of interest to correlate structural features of known indazole derivatives with specified HIF-1α inhibitory activity to map pharmacophoric features through Three-dimensional quantitative structural activity relationship (3D-QSAR) and pharmacophore mapping. Field and Gaussian based 3D-QSAR studies were performed to realize the variables influencing the inhibitory potency of HIF-1α inhibitors. Field and Gaussian- based 3D-QSAR models were validated through various statistical measures generated by partial least square (PLS). The steric and electrostatic maps generated for both 3D-QSAR provide a structural framework for designing new inhibitors. Further; 3D-maps were also helpful in understanding variability in the activity of the compounds. Pharmacophore mapping also generates a common five-point pharmacophore hypothesis (A₁D₂R₃R₄R₅_4) which can be employed in combination with 3D-contour maps to design potent HIF-1α inhibitors. Molecular docking and molecular dynamics (MD) simulation of the most potent compound 39 showed good binding efficiency and was found to be quite stable in the active site of the HIF-1α protein. The developed 3D-QSAR models; pharmacophore modelling; molecular docking studies along with the MD simulation analysis may be employed to design lead molecule as selective HIF-1α inhibitors for the treatment of Cancer.

PMID:35318905 | DOI:10.1080/07391102.2022.2051745

Behav Med. 2022 Mar 23:1-13. doi: 10.1080/08964289.2021.2021382. Online ahead of print.

ABSTRACT

The COVID-19 pandemic has drawn greater attention to social determinants of health and associated health inequities, which disproportionately affect vulnerable populations and places in the U.S. In this study, we explored geographic patterns of local-level COVID-19 vulnerability and associations with social and health determinants across Colorado. To conceptualize social and health determinants and how together they generate risk and exposure, we integrated the concepts of social vulnerability and syndemic to situate COVID-19 vulnerability within a broader hazards of place framework. Using geospatial statistics and GIS, we estimated census tract-level rates of COVID-19, which are not yet available in Colorado, and mapped areas of high and low incidence risk. We also developed composite indices that characterized social and health vulnerabilities to measure multivariate associations with COVID-19 rates. The findings revealed hotspots of persistent risk in mountain communities since the pandemic emerged in Colorado, as well as clusters of risk in the Urban Front Range’s central and southern counties, and across many parts of eastern Colorado. Vulnerability analyses indicate that COVID-19 rates were associated with mental health and chronic conditions along with social determinants that represent inequities in education, income, healthcare access, and race/ethnicity (minority percent of population), which may have disproportionately exposed some communities more than others to infection and severe health outcomes. Overall, the findings provide geographic health information about COVID-19 and vulnerability context, which may better inform local decision-making for interventions and policies that support equity of social determinants of health.Supplemental data for this article is available online at https://doi.org/10.1080/08964289.2021.2021382 .

PMID:35318900 | DOI:10.1080/08964289.2021.2021382

Ther Adv Respir Dis. 2022 Jan-Dec;16:17534666221087847. doi: 10.1177/17534666221087847.

ABSTRACT

BACKGROUND: During the novel coronavirus disease 2019 (COVID-19) pandemic raging around the world, the effectiveness of respiratory support treatment has dominated people’s field of vision. This study aimed to compare the effectiveness and value of high-flow nasal cannula (HFNC) with noninvasive ventilation (NIV) for COVID-19 patients.

METHODS: A comprehensive systematic review via PubMed, Web of Science, Cochrane, Scopus, WHO database, China Biology Medicine Disc (SINOMED), and China National Knowledge Infrastructure (CNKI) databases was conducted, followed by meta-analysis. RevMan 5.4 was used to analyze the results and risk of bias. The primary outcome is the number of deaths at day 28. The secondary outcomes are the occurrence of invasive mechanical ventilation (IMV), the number of deaths (no time-limited), length of intensive care unit (ICU) and hospital stay, ventilator-free days, and oxygenation index [partial pressure of arterial oxygen (PaO₂)/fraction of inhaled oxygen (FiO₂)] at 24 h.

RESULTS: In total, nine studies [one randomized controlled trial (RCT), seven retrospective studies, and one prospective study] totaling 1582 patients were enrolled in the meta-analysis. The results showed that the incidence of IMV, number of deaths (no time-limited), and length of ICU stay were not statistically significant in the HFNC group compared with the NIV group (ps = 0.71, 0.31, and 0.33, respectively). Whereas the HFNC group performed significant advantages in terms of the number of deaths at day 28, length of hospital stay and oxygenation index (p < 0.05). Only in the ventilator-free days did NIV show advantages over the HFNC group (p < 0.0001).

CONCLUSION: For COVID-19 patients, the use of HFNC therapy is associated with the reduction of the number of deaths at day 28 and length of hospital stay, and can significantly improve oxygenation index (PaO₂/FiO₂) at 24 h. However, there was no favorable between the HFNC and NIV groups in the occurrence of IMV. NIV group was superior only in terms of ventilator-free days.

PMID:35318888 | DOI:10.1177/17534666221087847

J Cosmet Laser Ther. 2022 Mar 23:1-5. doi: 10.1080/14764172.2022.2055079. Online ahead of print.

ABSTRACT

A picosecond-domain laser reportedly elicits positive treatment outcomes for acne scar and enlarged pores, but multiple sessions are often required. We sought to evaluate the efficacy of one-session fractional picosecond 1064-nm laser in treating atrophic acne scar and conspicuous pores. Fifty-nine acne scar patients with skin phototypes III and IV were treated with picosecond 1064-nm laser with microlens array (MLA) (8 mm spot, 0.8 J/cm², 10 Hz) for one session. The efficacy of acne scar was evaluated by Antera® 3D CS, whereas facial pore counts and diameter were evaluated by VISIA-CR and dermoscopic images, respectively. All measurements were performed at baseline, weeks 1, 2, 4 and 6. Acne scar volume and facial pore counts showed a statistically significant reduction at 1 week and subsequent follow-up period when compared to baseline (weeks 1-6; P < .001). The volume of acne scars and the number of enlarge pores decreased by 22.03% and 15.13%, respectively. Of note, there was no significant change in diameter of facial pores. The adverse events, including erythema and folliculitis, were mild and short-lived. A single session of picosecond 1064-nm laser with MLA was safe and effective in improving atrophic acne scar and the number of enlarged pores.

PMID:35318885 | DOI:10.1080/14764172.2022.2055079

Ann Med. 2022 Dec;54(1):858-866. doi: 10.1080/07853890.2022.2048884.

ABSTRACT

OBJECTIVES: The goal of this study is to analyse hospital costs and length of stay of patients admitted to psychiatric units in hospitals in a European region of the Mediterranean Arc. The aim is to identify the effects of comorbidities and other variables in order to create an explanatory cost model.

METHODS: In order to carry out the study, the Ministry of Health was asked to provide data on access to the mental health facilities of all hospitals in the region. Among other questions, this database identifies the most important diagnostic variables related to admission, like comorbidities, age and gender. The method used, based on the Manning-Mullahy algorithm, was linear regression. The results were measured by the statistical significance of the independent variables to determine which of them were valid to explain the cost of hospitalization.

RESULTS: Psychiatric inpatients can be divided into three main groups (psychotic, organic and neurotic), which have statistically significant differences in costs. The independent variables that were statistically significant (p <.05) and their respective beta and confidence intervals were: psychotic group (19,833.0 ± 317.3), organic group (9,878.4 ± 276.6), neurotic group (11,060.1 ± 287.6), circulatory system diseases (19,170 ± 517.6), injuries and poisoning (21,101.6 ± 738.7), substance abuse (20,580.6 ± 514, 6) and readmission (19,150.9 ± 555.4).

CONCLUSIONS: Unlike most health services, access to psychiatric facilities does not correlate with comorbidities due to the specific nature of this specialization. Patients admitted to psychosis had higher costs and a higher number of average staysKEY MESSAGESThe highest average hospital expenditure occurred in patients admitted for psychotic disorders.Due to the particularities of psychiatry units and unlike other medical specialties, the number of comorbidities did not influence the number of hospital stays or hospital expenditure.Apart from the main diagnostic group, the variables that were useful to explain hospital expenditure were the presence of poisoning and injuries as comorbidity, diseases of circulatory system as comorbidity, history of substance abuse and readmission.

PMID:35318876 | DOI:10.1080/07853890.2022.2048884

Zh Nevrol Psikhiatr Im S S Korsakova. 2022;122(3. Vyp. 2):59-62. doi: 10.17116/jnevro202212203259.

ABSTRACT

OBJECTIVE: To evaluate the effect of Mexidol on the recovery of cognitive functions in patients after ischemic stroke (IS).

MATERIAL AND METHODS: We examined 70 patients with acute IS, who were randomized into 2 groups by random sampling; The 1st group consisted of patients who, against the background of the main standard therapy for 14 days, received Mexidol intravenously, 500 mg 1 time per day, followed by oral administration of Mexidol FORTE 250, 750 mg per day for 60 days (40 patients; 28 men, 12 women). Group 2 consisted of 30 patients (21 men, 9 women) who received only standard therapy.

RESULTS: Baseline scores on the MoCA and MMSE scales did not differ between the two groups. Retesting showed that the improvement on these scales was statistically more significant in the 1st group. The analysis of indicators of the evoked potential P300 confirmed a more pronounced positive trend in the 1st group (p<0.01).

CONCLUSION: The use of sequential therapy with Mexidol is accompanied by a more complete recovery of cognitive functions in patients who have undergone IS.

PMID:35318844 | DOI:10.17116/jnevro202212203259

Geospat Health. 2022 Mar 22;17(s1). doi: 10.4081/gh.2022.1070.

ABSTRACT

After a two-year pandemic, coronavirus disease 2019 (COVID-19) is still a serious public health problem and economic stability worldwide, particularly in the Association of Southeast Asian Nations (ASEAN) countries. The objective of this study was to identify the wave periods, provide an accurate space-time forecast of COVID-19 disease and its relationship to vaccination rates. We combined a hierarchical Bayesian pure spatiotemporal model and locally weighted scatterplot smoothing techniques to identify the wave periods and to provide weekly COVID-19 forecasts for the period 15 December 2021 to 5 January 2022 and to identify the relationship between the COVID-19 risk and the vaccination rate. We discovered that each ASIAN country had a unique COVID-19 time wave and duration. Additionally, we discovered that the number of COVID-19 cases was quite low and that no weekly hotspots were identified during the study period. The vaccination rate showed a nonlinear relationship with the COVID-19 risk, with a different temporal pattern for each ASEAN country. We reached the conclusion that vaccination, in comparison to other interventions, has a large influence over a longer time span.

PMID:35318835 | DOI:10.4081/gh.2022.1070

Cancer Med. 2022 Mar 22. doi: 10.1002/cam4.4671. Online ahead of print.

ABSTRACT

Accumulating evidence indicates that alterations of gut microbiota are associated with colorectal cancer (CRC). Therefore, the use of gut microbiota for the diagnosis of CRC has received attention. Recently, several studies have been conducted to detect the differences in the gut microbiota between healthy individuals and CRC patients using machine learning-based gut bacterial DNA meta-sequencing analysis, and to use this information for the development of CRC diagnostic model. However, to date, most studies had small sample sizes and/or only cross-validated using the training dataset that was used to create the diagnostic model, rather than validated using an independent test dataset. Since machine learning-based diagnostic models cause overfitting if the sample size is small and/or an independent test dataset is not used for validation, the reliability of these diagnostic models needs to be interpreted with caution. To circumvent these problems, here we have established a new machine learning-based CRC diagnostic model using the gut microbiota as an indicator. Validation using independent test datasets showed that the true positive rate of our CRC diagnostic model increased substantially as CRC progressed from Stage I to more than 60% for CRC patients more advanced than Stage II when the false positive rate was set around 8%. Moreover, there was no statistically significant difference in the true positive rate between samples collected in different cities or in any part of the colorectum. These results reveal the possibility of the practical application of gut microbiota-based CRC screening tests.

PMID:35318827 | DOI:10.1002/cam4.4671

Neuropsychopharmacol Rep. 2022 Mar 22. doi: 10.1002/npr2.12247. Online ahead of print.

ABSTRACT

OBJECTIVES: Understanding how local “psychiatry clinic” characteristics shape research findings is essential for applying research into evolution, outcomes, and costs of mental health. However, a paucity of “psychiatry clinics” details has implications for the interpretation and utilization of this research.

METHODS: We reviewed data of 746 patients with new-onset schizophrenia on antipsychotic monotherapy seen over four years in an “adult psychiatry clinic” at Jazan Health, Saudi Arabia. Protocol-driven interviews and investigations were recorded prospectively and extracted from the medical records for the study. Summary statistics and logistic regression analyses were applied to assess patients’ characteristics and outcomes.

RESULTS: The median patient age was 32 (IQR 27-39) years. Of patients, 589 (79.0%) were male, and 679 (91.0%) had a low-level education. The median follow-up duration was 51.4 (IQR 27.4-96.3) weeks. The most used initial antipsychotic drugs were olanzapine (48.8%), haloperidol (13.9%), and aripiprazole (11.3%). The numbers of patients who retained the initial drug at 24 and 52 weeks were 539 (72.3%) and 325 (43.6%), respectively. The initial drug was changed in 246 (33.0%) patients. The median time to initial drug change was 43.9 (IQR 14.8-85.0) weeks. The logistic regression demonstrated that male sex (P < 0.004), young adult age group (P < 0.027), predominant positive symptoms (P < 0.021), treatment with haloperidol (P < 0.024), and khat use (P < 0.006) were significant factors for drug change.

CONCLUSIONS: This clinical records study demonstrated substantial individual variations in characteristics and in responding to initial antipsychotic medication. Insight into these findings will facilitate the planning for comprehensive research programs.

PMID:35318823 | DOI:10.1002/npr2.12247

Matern Child Nutr. 2022 Mar 22:e13352. doi: 10.1111/mcn.13352. Online ahead of print.

ABSTRACT

There is limited information on the feeding practices of 9.42 million children living within institution-based care (IBC) worldwide. Poor feeding practices can predispose or exacerbate malnutrition, illness and disability. Here we describe the feeding practices of children living within IBC based on a retrospective analysis of records from 3335 children, 0-18 years old, participating in Holt International’s Child Nutrition Program (CNP), from 36 sites in six countries. Data analysed included demographic information on age, sex, feeding practices, disabilities and feeding difficulties. Descriptive statistics were produced. A generalised linear model explored associations between feeding difficulties and disability and 2 × 2 tables examined feeding difficulties over time. An additional set of feeding observations with qualitative and quantitative data was analysed. At baseline, the median age of children was 16 months (0.66-68 months) with 1650/3335 (49.5%) females. There were 757/3335 (22.7%) children with disabilities; 550/984 (55.9%) were low birth weight; 311/784 (39.7%) were premature; 447/3113 (14.4%) had low body mass index and 378/3335 (11.3%) had feeding difficulties. The adjusted risk of having a feeding difficulty was 5.08 ([95% confidence interval: 2.65-9.7], p ≤ 0.001) times greater in children with disabilities than those without. Many children saw their feeding difficulties resolve after 1-year in CNP, 54/163 (33.1%) for children with disabilities and 57/106 (53.8%) for those without disabilities. Suboptimal hygiene, dietary and feeding practices were reported. In conclusion, feeding difficulties were common in IBC, especially among children with disabilities. Supporting safe interactive mealtimes for children living within IBC should be prioritised, to ensure overall health and development.

PMID:35318809 | DOI:10.1111/mcn.13352