Nevin Manimala

J Biomol Struct Dyn. 2022 Sep 9:1-17. doi: 10.1080/07391102.2022.2114938. Online ahead of print.

ABSTRACT

A series of novel 3-phenyl-1-(alkylphenyl)-9-oxa-4-azaphenanthren-10-ones and (E)-1-phenyl-3-(aryl)prop-2-en-1-ones were synthesized and characterized by IR, ¹H NMR, ¹³C spectroscopy and elemental analysis. The synthesized Compounds 5a-f were subjected to molecular docking simulation with three proteins, namely, tyrosyl-tRNA synthetase, heme oxygenase 1 and acetylcholinesterase to evaluate the antibacterial, antioxidant and acetylcholinesterase inhibition, respectively. Moreover, the docked poses of all compounds inside the proteins were subjected to further dynamic simulation through the calculation of the binding free energy using MM-GBSA analysis. Compound 5d exhibits high potential inhibition against antibacterial, antioxidant and acetylcholinesterase activities. Compounds 3d, 3f, 5a and 5d recorded an important scavenging activity in DPPH and ABTS assays. Investigation of the anti-acetylcholinesterase activity of the synthesized compounds showed that Compounds 5a and 3d are the most potent inhibitors against AchE, with percent inhibition values of 38 and 30%, respectively.Communicated by Ramaswamy H. Sarma.

PMID:36082583 | DOI:10.1080/07391102.2022.2114938

Ir J Psychol Med. 2022 Sep 9:1-8. doi: 10.1017/ipm.2022.40. Online ahead of print.

ABSTRACT

OBJECTIVES: Studies on patient-student relationships have to date largely focused on student attitudes. This study explores attitudes of patients with psychiatric illness in Ireland, towards medical students. Patients’ experience of consent for student involvement is an area of concern in previous studies and is also quantified here.

METHODS: This was a mixed-methods cross-sectional survey of Irish adult psychiatric patients. Quantitative analysis was carried out using SPSS 22 (Statistical Product and Service Solutions, Version 22, IBM). Differences on Likert score between groups (male/female, hospital site, past experience with students/ no experience) were analysed using ordinal logistic regression with a p-value below 0.05 being significant. Qualitative data were analysed by thematic analysis using OpenCode 4.03.

RESULTS: A total of 340 patients completed the survey. The mean age (sd) was 44.8 (16.3). 52.8% were female, 75.2% were outpatients. 24.3% had never met a medical student. Most patients were comfortable seeing students, but preferred students being passive observers. Patients with previous student experience had higher comfort levels and more positive attitudes. Although most patients (63.7%) strongly agreed they had been asked for consent, only 49.3% felt they had been given sufficient information. Qualitative data revealed preference for adequate information and notice of involvement. Patients felt pressured by student presence in certain circumstances.

CONCLUSIONS: Psychiatric patients are comfortable with students but many feel inadequately informed. Patients recognise the benefits of interacting with students. More information is needed regarding circumstances in which patients give consent to involvement with students.

PMID:36082526 | DOI:10.1017/ipm.2022.40

Mil Med. 2022 Sep 9:usac267. doi: 10.1093/milmed/usac267. Online ahead of print.

ABSTRACT

INTRODUCTION: The U.S. Navy offers an attractive opportunity for residency training in orthopedic surgery. The factors that Navy orthopedic residency program leadership finds important in applicant selection for training have not been reported. Additionally, data regarding the academic competitiveness of recently matched applicants have not been previously published. This study presents the results of two surveys administered to all navy orthopedic program directors and department chairmen, as well as data for United States Medical Licensing Examination (USMLE) Steps 1 and 2, medical school class percentile, leadership responsibilities, research endeavors, and letters of recommendation of both matched and unmatched applicants.

MATERIALS AND METHODS: Two anonymous surveys were administered to all program directors and department chairmen at Navy orthopedic residency training programs with questions designed to gauge perceived importance of various application factors when selecting for the match. The results were compiled, and mean levels of importance were reported. Deidentified data were collected on all applicants to Navy orthopedic residency programs from 2015 to 2019. Data points specific to USMLE Step 1 and 2 board scores, medical school class percentile, research, leadership, and letters of recommendation were analyzed using single and multiple logistic regression analyses, and odds ratios for each variable were calculated.

RESULTS: Navy leadership unanimously expressed that clerkship performance at the individual program director’s institution was most important, followed by Steps 1 and 2 licensing examination scores. Single logistic regression analyses showed that Step 1 score and clinical, leadership, and recommendation scores were statistically significant. When controlled for Step 1 score, only academic performance and leadership scores maintained statistical significance.

CONCLUSIONS: Applicants to Navy orthopedic surgery residency programs should strive to be competitive in all aspects of their application, with specific emphasis placed on outstanding performance during orthopedic clerkships, demonstration of leadership characteristics, and academic excellence. With transition to a pass/fail grading system for Step 1, there will be more emphasis on other measures of academic success, such as Step 2 scores and clinical clerkship grades.

PMID:36082505 | DOI:10.1093/milmed/usac267

J Biomech Eng. 2022 Sep 9. doi: 10.1115/1.4055564. Online ahead of print.

ABSTRACT

Musculoskeletal modelling and simulation has been an emerging trend in human gait analysis. It allows the user to isolate certain biomechanical condition and elucidate the dynamics of joints and muscles. This study used an open source musculoskeletal modelling and simulation tool, OpenSim to investigate the biomechanical effect of knee brace. It collected gait data from thirty-eight participants and examined the gait spatio-temporal parameters, joint angles and joint moments. Static optimization was performed to estimate the lower extremity muscle force. Statistical analysis was conducted to identify the difference between normal and abnormal gaits. The results demonstrated the feasibility of this method to investigate the interaction and coordination of lower extremity joints and muscles. The knee brace constrained the range of the motion of the knee during walking. It also changed the walking speed, step length and stance-to-swing ratio. Several significant differences were found in the joint moments and muscle forces of the rectus femoris, gastrocnemius, soleus and tibialis anterior. Musculoskeletal modelling and simulation tool offers a less invasive and practical alternative to analyze human motion. It also offers a means to investigate the effect of medical devices such as knee brace, which can be potentially beneficial for the future design and development of such devices and for derivation of rehabilitation treatment to improve patient’s gait.

PMID:36082472 | DOI:10.1115/1.4055564

J Clin Lab Anal. 2022 Sep;36(9):e24642. doi: 10.1002/jcla.24642. Epub 2022 Aug 10.

ABSTRACT

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease often accompanied by rapidly progressive renal failure, and the genetic background is still unknown. Our study was performed to test whether autophagy-related 16 like 1 (ATG16L1) rs4663402 and rs4663396 single nucleotide polymorphisms (SNPs) were associated with AAV in the Chinese Guangxi population.

METHODS: One hundred seventy seven unrelated AAV patients and 216 healthy controls were included in this case-control study. Multiplex polymerase chain reaction combined with high-throughput sequencing was used for typing, and SNPStats and SHEsis were used for association analysis, pairwise linkage disequilibrium, and haplotype analysis.

RESULTS: rs4663402 and rs4663396 were in Hardy-Weinberg equilibrium in AAV and control groups. The frequencies of rs4663402 AA, AT, and TT genotypes were 82.5%, 16.9%, and 0.6%, respectively, in patients with AAV, and 83.5%, 16.2%, and 0.5%, respectively, in controls. The frequencies of rs4663396 CC, CT, and TT genotypes were 63.8%, 33.9%, and 2.3%, respectively, in patients with AAV, and 69.2%, 26.6%, and 4.2%, respectively, in controls. Haplotype analysis revealed two SNPs in a single haplotype block (D’ = 1.0). Our logistic regression adjusted for sex and age showed no association between rs4663402 and rs4663396 and the risk for AAV in genetic models (p > 0.05). However, ATG16L1 rs4663396 CC and CT + TT genotypes exhibited statistically significant differences in the incidence of arthralgia (p = 0.03).

CONCLUSIONS: Our results indicated that ATG16L1 rs4663402 and rs4663396 polymorphisms were not associated with AAV in the Chinese Guangxi population. ATG16L1 rs4663396 CT + TT genotype may be associated with arthralgia.

PMID:36082465 | DOI:10.1002/jcla.24642

J Clin Lab Anal. 2022 Sep;36(9):e24645. doi: 10.1002/jcla.24645. Epub 2022 Aug 5.

ABSTRACT

BACKGROUND: Pregnancy is a prothrombotic condition which can be abnormally exaggerated in women with thrombophilia.

METHODS: In a prospective study, patients who delivered at term, by cesarean section, between 1 October 2017 and 1 December 2021, who already had a diagnosis of thrombophilia before coming to our hospital, were included in the study group (n = 80). A similar number of nonthrombophilia patients (n = 80) without any history of thrombotic events, age- and para-matched with the study group, were included in the control group. The postpartum uterine ultrasonographic scale (PUUS) values, in the first 24-48 h, were correlated with the patients’ data.

RESULTS: The P-LCR (platelet large cell ratio), was significantly higher in the treated thrombophilia group (p = 0.042). There was no correlation between PUUS and complete blood count values, coagulation factors, maternal characteristics, or fetal outcomes, except for postpartum neutrophils (p = 0.047) and postpartum platelet count (p = 0.046).

CONCLUSIONS: Postpartum uterine involution was not significantly different, after cesarean section, between treated thrombophilia patients and nonthrombophilia patients. Involution correlated only with postpartum neutrophils and postpartum platelet count.

PMID:36082463 | DOI:10.1002/jcla.24645

Arthritis Rheumatol. 2022 Sep 9. doi: 10.1002/art.42339. Online ahead of print.

ABSTRACT

OBJECTIVES: Gout patients often have multiple comorbidities, making them susceptible to SARS-CoV-2 infection and its severe outcomes; however, few studies have examined the association between gout and the risk of SARS-CoV-2 infection and its severe sequelae, especially after COVID-19 vaccination.

METHODS: We conducted two cohort studies using The Health Improvement Network. Individuals with gout and those without gout from the general population were followed from December 8^th , 2020, to October 31^st , 2021. We estimated the rate difference (RD) and hazard ratio (HR) of SARS-CoV-2 infection and its severe outcomes (i.e., hospitalization and death over 30 days after SARS-CoV-2 infection) for individuals with gout versus those without gout using Cox proportional hazard model according to COVID-19 vaccination status. We adjusted potential confounders using overlap weighting of exposure score.

RESULTS: Among the vaccinated cohort, 1,955 cases of breakthrough infection occurred in 54,576 individuals with gout (4.68/1000 person-months) and 52,468 cases in 1,336,377 individuals without gout (3.76/1000 person-months). The adjusted RD of breakthrough infection was 0.91 (95%CI: 0.62-1.20)/1000 person-months, and the adjusted HR was 1.24 (95%CI: 1.19-1.30). Gout was also associated with an increased risk of hospitalization (adjusted HR=1.30, 95%CI: 1.10-1.53) and death (adjusted HR=1.36, 95%CI: 0.87-2.13). Women with gout showed an increased risk of hospitalization (adjusted HR 1.55, 95%CI: 1.15-2.10) and death (adjusted HR=2.46, 95%CI: 1.12-5.41). Similar associations with gout were observed in the unvaccinated cohort.

CONCLUSIONS: These general population data suggest that individuals with gout, especially women, have higher risks of both SARS-CoV-2 infection and severe sequelae, even with vaccinations. This article is protected by copyright. All rights reserved.

PMID:36082457 | DOI:10.1002/art.42339

Int J Cancer. 2022 Sep 8. doi: 10.1002/ijc.34278. Online ahead of print.

ABSTRACT

Pleiotropy, which consists of a single gene or allelic variant affecting multiple unrelated traits, is common across cancers, with evidence for genome-wide significant loci shared across cancer and non-cancer traits. This feature is particularly relevant in multiple myeloma (MM) because several susceptibility loci that have been identified to date are pleiotropic. Therefore, the aim of this study was to identify novel pleiotropic variants involved in MM risk using 28,684 independent single nucleotide polymorphisms (SNPs) from GWAS Catalog that reached a significant association (P<5×10^-8 ) with their respective trait. The selected SNPs were analyzed in 2,434 MM cases and 3,446 controls from the International Lymphoma Epidemiology Consortium (InterLymph). The 10 SNPs showing the strongest associations with MM risk in InterLymph were selected for replication in an independent set of 1,955 MM cases and 1,549 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and 418 MM cases and 147,282 controls from the FinnGen project. The combined analysis of the three studies identified an association between DNAJB4-rs34517439-A and an increased risk of developing MM (OR=1.22, 95%CI 1.13-1.32, P=4.81×10^-7 ). rs34517439-A is associated with a modified expression of the FUBP1 gene, which encodes a multifunctional DNA and RNA-binding protein that it was observed to influence the regulation of various genes involved in cell cycle regulation, among which various oncogenes and oncosuppressors. In conclusion, with a pleiotropic scan approach we identified DNAJB4-rs34517439 as a potentially novel MM risk locus. This article is protected by copyright. All rights reserved.

PMID:36082445 | DOI:10.1002/ijc.34278

Hand (N Y). 2022 Sep 8:15589447221122822. doi: 10.1177/15589447221122822. Online ahead of print.

ABSTRACT

BACKGROUND: Posterior interosseous nerve (PIN) compression in the forearm without motor paralysis is a challenging clinical diagnosis. This retrospective study evaluated the clinical assessment, diagnostic studies, and outcomes following surgical decompression of the PIN in the forearm.

METHODS: This study reviewed 182 patients’ medical charts following PIN decompression between 2000 and 2020 by a single surgeon. After exclusion of combined nerve entrapments, polyneuropathy, motor palsy, or lateral epicondylitis, the study included 14 patients. Data collected included: clinical presentation and pain drawings, provocative testing, functional outcomes, and Disabilities of the Arm, Shoulder, and Hand (DASH) scores.

RESULTS: There were 15 PIN decompressions (14 patients, mean follow-up = 11.9 months). Clinical presentation included pain (n = 14) (proximal dorsal forearm, n = 14; distal forearm over radial sensory nerve, n = 3) and positive clinical tests (sensory collapse test over the radial tunnel, n = 8; pain with forearm pronation and compression over the radial tunnel, n = 10; Tinel sign, n = 5). Postoperatively, there were significant improvements in Visual Analog Scale pain scores (6.7 to 3.3, P = .0006), quality-of-life scores (74.7 to 32.7, P = .0001), and DASH scores (46.3 to 33.6, P = .02).

CONCLUSIONS: The PIN compression in the forearm without motor paralysis is a clinical diagnosis supported by pain drawings, pain quality, and provocative tests. Patients with persistent, therapy-resistant dorsal forearm pain should be evaluated for PIN compression. Surgical decompression provides statistically significant quantifiable improvement in pain and quality of life.

PMID:36082441 | DOI:10.1177/15589447221122822

J Cheminform. 2022 Sep 9;14(1):61. doi: 10.1186/s13321-022-00642-3.

ABSTRACT

Extraction of chemical formulas from images was not in the top priority of Computer Vision tasks for a while. The complexity both on the input and prediction sides has made this task challenging for the conventional Artificial Intelligence and Machine Learning problems. A binary input image which might seem trivial for convolutional analysis was not easy to classify, since the provided sample was not representative of the given molecule: to describe the same formula, a variety of graphical representations which do not resemble each other can be used. Considering the variety of molecules, the problem shifted from classification to that of formula generation, which makes Natural Language Processing (NLP) a good candidate for an effective solution. This paper describes the evolution of approaches from rule-based structure analyses to complex statistical models, and compares the efficiency of models and methodologies used in the recent years. Although the latest achievements deliver ideal results on particular datasets, the authors mention possible problems for various scenarios and provide suggestions for further development.

PMID:36076301 | DOI:10.1186/s13321-022-00642-3