Nevin Manimala

J Mol Model. 2021 Apr 17;27(5):128. doi: 10.1007/s00894-021-04732-1.

ABSTRACT

The COVID-19 main protease (Mpro), one of the conserved proteins of the novel coronavirus is crucial for its replication and so is a very lucrative drug target. Till now, there is no drug molecule that has been convincingly identified as the inhibitor of the function of this protein. The current pandemic situation demands a shortcut to quickly reach to a lead compound or a drug, which may not be the best but might serve as an interim solution at least. Following this notion, the present investigation uses virtual screening to find a molecule which is alraedy approved as a drug for some other disease but could be repurposed to inhibit Mpro. The potential of the present method of work to identify such a molecule, which otherwise would have been missed out, lies in the fact that instead of just using the crystallographically identified conformation of the receptor’s ligand binding pocket, molecular dynamics generated ensemble of conformations has been used. It implicitly included the possibilities of “induced-fit” and/or “population shift” mechanisms of ligand fitting. As a result, the investigation has not only identified antiviral drugs like ribavirin, ritonavir, etc., but it has also captured a wide variety of drugs for various other diseases like amrubicin, cangrelor, desmopressin, diosmin, etc. as the potent possibilities. Some of these ligands are versatile to form stable interactions with various different conformations of the receptor and therefore have been statistically surfaced in the investigation. Overall the investigation offers a wide range of compounds for further testing to confirm their scopes of applications to combat the COVID-19 pandemic.

PMID:33864532 | DOI:10.1007/s00894-021-04732-1

Behav Genet. 2021 Apr 17. doi: 10.1007/s10519-021-10057-9. Online ahead of print.

NO ABSTRACT

PMID:33864530 | DOI:10.1007/s10519-021-10057-9

Arch Gynecol Obstet. 2021 Apr 17. doi: 10.1007/s00404-021-06043-5. Online ahead of print.

ABSTRACT

PURPOSE: To assess the efficacy of phloroglucinol for acceleration of labour.

METHODS: Randomized controlled trials (RCTs) comparing phloroglucinol with placebo were searched in PubMed, Embase and the Cochrane Library. Literatures were collected up to April 2020. Primary outcomes were the duration of labour and average blood loss. Finally, a total of 4 RCTs, 377 patients were included in this meta-analysis. The included RCTs were analyzed by the software Rev Man 5. 3.

RESULTS: In the phloroglucinol group, the duration of the first stage was reduced by 116.04 min (95% CI 107.71 to 124.68), and the duration of the second stage was reduced by 10.75 min (95% CI 8.79 to 12.70). The average blood loss was reduced by 16.07 ml, which was statistically different from the control group.

CONCLUSION: The application of phloroglucinol is proved to be effective for accelerating the labour process, reducing the risk of maternal and neonatal complications.

PMID:33864511 | DOI:10.1007/s00404-021-06043-5

Int Arch Occup Environ Health. 2021 Apr 17. doi: 10.1007/s00420-021-01694-y. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine if exposure to cold environments, during work or leisure time, was associated with increased reporting of airway symptoms in the general population of northern Sweden.

METHODS: Through a population-based postal survey responded to by 12627 subjects, ages 18-70, living in northern Sweden, the occurrence of airway symptoms was investigated. Cold exposure during work or leisure time was self-reported on numerical rating scales. Binary logistic regression was used to determine the statistical association between cold exposure and airway symptoms.

RESULTS: For currently working subjects (N = 8740), reporting any occupational cold exposure was associated to wheeze (OR 1.3; 95% CI 1.1-1.4); chronic cough (OR 1.2; 95% CI 1.1-1.4); and productive cough (OR 1.3; 95% CI 1.1-1.4), after adjusting for gender, age, body mass index, daily smoking, asthma, and chronic obstructive pulmonary disease. Leisure-time cold exposure was not significantly associated to reporting airway symptoms.

CONCLUSIONS: Occupational cold exposure was an independent predictor of airway symptoms in northern Sweden. Therefore, a structured risk assessment regarding cold exposure could be considered for inclusion in the Swedish workplace legislation.

PMID:33864489 | DOI:10.1007/s00420-021-01694-y

Eur Arch Otorhinolaryngol. 2021 Apr 17. doi: 10.1007/s00405-021-06818-1. Online ahead of print.

ABSTRACT

PURPOSE: Evaluate the impact of perennial allergic rhinitis (PAR) on the health-related quality of life (HRQL) and measure performance issues that are of major concerns for PAR patients, as well as determining the effect of intra-nasal steroids (INS) on PAR and associated congestion, sleep complaints, and daytime sleepiness.

METHODS: This study was a cross-sectional study. A total of 78 PAR patients underwent otorhinolaryngological examination and skin test. All participants filled in the Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire (NRQLQ), the Stanford Sleepiness Scale (SSS), and the Epworth Sleepiness Scale (ESS). Participants were asked to undergo treatment with Budesonide (BUD) topical aqueous nasal spray for eight weeks. After the treatment period, all participants were again asked to answer the three questionnaires.

RESULTS: The results of this study found statistically significant improvements in the overall NRQLQ score (p < 0.001) and individual NRQLQ domain scores (p < 0.05) after INS treatment. A statistically significant reduction in symptom severity in the four NRQLQ domains before and after treatment was found (p < 0.05), except for restlessness, post-nasal drip, and avoiding symptom triggers (p = 0.575, 0.172, and 0.705, respectively). There was a statistically significant difference in ESS and SSS scores before and after treatment (p < 0.001).

CONCLUSION: PAR has a significant impact on sleep quality and, as a result, a lower QOL. This study demonstrates that INS is an effective modality in the treatment of PAR and positively impacts patients’ QOL by improving nasal symptoms, daytime fatigue, and somnolence, and sleep quality.

PMID:33864483 | DOI:10.1007/s00405-021-06818-1

Int Urogynecol J. 2021 Apr 17. doi: 10.1007/s00192-021-04783-1. Online ahead of print.

ABSTRACT

INTRODUCTION AND HYPOTHESIS: We hypothesized that differences in post-partum levator hiatus (LH) measurements, as well as the area of urethra and bladder (AUB), viewed under ultrasound, correlate with diastasis rectus abdominis (DRA) occurrence. The primary objective of this study is to determine ultrasound parameters available for diagnosing DRA in post-partum women. We compared LH and AUB measurements under ultrasound in primiparous women, with and without DRA, at 24-26 weeks postpartum.

METHODS: One hundred ninety-four women underwent routine examination, including a self-made clinical symptoms questionnaire, DRA evaluation, and LH and AUB measurements. Independent samples t- and chi-squared tests were used to compare the differences between women with and without DRA.

RESULTS: DRA incidence was significantly higher among those who underwent cesarean section (CS) than for vaginal delivery (VD) (P = 0.038). DRA patients could potentially have urinary urgency, frequency, pain, dysuria, and perineal tears. Additionally, statistically significant differences were found between VD patients, with or without DRA, in the resting LH transverse diameter (TrD) (P = 0.032) and the area of the levator hiatus (ALH) (P = 0.048) as well as AUB at Valsalva (P = 0.049). No differences, however, were found between the DRA and no DRA groups for all those measurements among women who had cesarean deliveries.

CONCLUSIONS: DRA was more likely in post-CS women. Furthermore, the results showed a plausible association between DRA occurrence and LH expansion, especially in women with VD under rest and Valsalva. This could be useful for developing therapeutic plans based on these parameters for post-partum rehabilitation of women with DRA to avoid long-term complications.

PMID:33864477 | DOI:10.1007/s00192-021-04783-1

Int Urogynecol J. 2021 Apr 17. doi: 10.1007/s00192-021-04797-9. Online ahead of print.

ABSTRACT

INTRODUCTION AND HYPOTHESIS: The purpose of this article is to understand that the majority of studies investigating the role of risk factors for maternal birth trauma and pelvic floor disorders are designed using causal inferential statistical methods and have not been designed to investigate the more useful goal of clinical prediction.

METHODS: A review of the literature was conducted to describe notable causal and predictive associations between risk factors and maternal birth trauma outcomes. Examples were obtained to illustrate and contrast differences in clinical usefulness between causal and predictive models.

RESULTS: Effects of pregnancy and childbirth on the risk of maternal birth trauma outcomes and subsequent pelvic floor disorders are an area of profound investigation. Numerous observational studies provide evidence that pregnancy and childbirth play a causal role in the increasing prevalence of these outcomes, and clinicians must rely on this observational evidence to guide decisions about preventing maternal birth trauma and pelvic floor disorders. However, there are important differences between the design and evaluation of models for a predictive context including: study design goals, inclusion or exclusion of candidate risk factors, model evaluation and the additional need to assess model error.

CONCLUSION: This article contrasts how causal and predictive modeling approaches are different and argues that indiscriminately modeling risk factors for birth trauma and pelvic floor disorder outcomes is costly to women.

PMID:33864475 | DOI:10.1007/s00192-021-04797-9

Int Urogynecol J. 2021 Apr 17. doi: 10.1007/s00192-021-04710-4. Online ahead of print.

ABSTRACT

INTRODUCTION AND HYPOTHESIS: While pelvic organ prolapse is common in clinical observation, there is a lack of evidence regarding its actual proportion and associated factors in the study area. Understanding the prevalence and risk factors could potentially help with prevention. Thus, this study aimed to determine the prevalence and associated factors related to pelvic organ prolapse in the Amhara region, northwest Ethiopia.

METHODS: An institutional-based cross-sectional study was conducted among 424 women, recruited by the systematic random sampling technique. Data were collected in a face-to-face interview using a structured and pre-tested questionnaire to assess the symptoms of pelvic organ prolapse and the socio-demographic, obstetric, gynecologic, medical and surgical characteristics. The stage of prolapse was determined by pelvic examination using the Simplified Pelvic Organ Prolapse Quantification staging system. Descriptive statistics and logistic regression analyses were employed.

RESULTS: The overall prevalence of pelvic organ prolapse (stage I-IV) was found to be 37.6% when determined by pelvic examination and 9.2% as assessed by prolapse symptoms. Age ≥ 40 years [AOR 2.46 (1.320, 5.314)], age at first delivery ≤ 20 years [AOR 4.719 (2.44, 9.11)], carrying heavy objects for ≥ 5 hours a day [AOR 12.724 (4.89, 33.07)], parity ≥ 4 [AOR 3.739 (1.693, 8.208)], prolonged labor [AOR 3.487 (1.699, 7.159)], constipation [AOR 2.835 (1.273, 6.317)] and anemia [AOR 2.22 (1.049, 4.694)] were significantly associated with pelvic organ prolapse.

CONCLUSION: Prevalence of pelvic organ prolapse is high in the area; thus, developing information and education programs on avoiding risk factors is advisable to reduce the problem.

PMID:33864474 | DOI:10.1007/s00192-021-04710-4

Indian Pediatr. 2021 Apr 17:S097475591600311. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the prognostic value of amplitude-integrated EEG in term neonates with encephalopathy.

METHODS: In this prospective observational study we enrolled 58 term neonates with encephalopathy from March, 2019 to March, 2020. Level of alertness was ascertained as per Volpe’s classification and tone as per Amiel-Tison scale of tone assessment. Abnormal aEEG was defined as background activity other than continuous normal voltage, or immature or absent sleep-wake cycle, or presence of electrical seizure. Primary outcome was abnormal neurological examination at discharge and/or death prior to discharge.

RESULTS: Out of 58 neonates, aEEG was abnormal for 50 (86.2%). There was a statistically significant association between abnormal aEEG findings and primary outcome (P=0.04). The aEEG score cut-off of >2 had satisfactory sensitivity (88.8%) and specificity (79.5%) to predict primary outcome.

CONCLUSIONS: Abnormal aEEG had good sensitivity but low specificity to predict primary outcome in term neonates with encephalopathy.

PMID:33864450

Proteomics Clin Appl. 2021 Apr 17:e2100002. doi: 10.1002/prca.202100002. Online ahead of print.

ABSTRACT

OBJECTIVE: We aim to investigate the changes of plasma proteome among mild, severe AIS patients and healthy controls.

METHODS: In this retrospective study, 84 individuals including 56 confirmed AIS patients (27 follow-up AIS patients and 29 surgical AIS patients) and another 28 healthy teenagers. Plasma samples were obtained and Quadrupole-Orbitrap Mass Spectrometer was performed to identify proteins in AIS patients and control group. T-test and ANOVA were performed to screen for differential proteins. GO and KEGG pathway, Pearson’s correlation analysis and PLS model were applied to identify enriched proteins, investigate correlation between proteins and Cobb angles. ELISA was performed to further verify the quantitative proteomics results.

RESULTS: A total of 349 proteins were identified, among which 55 protein levels changed significantly in AIS group, compared with control group. Post hoc test indicated 36 proteins were significantly different between surgical and control group, 35 proteins between follow-up and control group. Fibronectin, fibrinogen and calmodulin were statistically different among three groups through MS and were positively correlated with the Cobb angle.

CONCLUSIONS: We performed the proteomic study and revealed that fibronectin, fibrinogen and calmodulin might not only be considered as biomarkers for AIS but could be correlated with curve severity. This article is protected by copyright. All rights reserved.

PMID:33864425 | DOI:10.1002/prca.202100002