Nevin Manimala

mSystems. 2021 Oct 26;6(5):e0009521. doi: 10.1128/mSystems.00095-21. Epub 2021 Oct 26.

ABSTRACT

The novel coronavirus SARS-CoV-2, which emerged in late 2019, has since spread around the world and infected hundreds of millions of people with coronavirus disease 2019 (COVID-19). While this viral species was unknown prior to January 2020, its similarity to other coronaviruses that infect humans has allowed for rapid insight into the mechanisms that it uses to infect human hosts, as well as the ways in which the human immune system can respond. Here, we contextualize SARS-CoV-2 among other coronaviruses and identify what is known and what can be inferred about its behavior once inside a human host. Because the genomic content of coronaviruses, which specifies the virus’s structure, is highly conserved, early genomic analysis provided a significant head start in predicting viral pathogenesis and in understanding potential differences among variants. The pathogenesis of the virus offers insights into symptomatology, transmission, and individual susceptibility. Additionally, prior research into interactions between the human immune system and coronaviruses has identified how these viruses can evade the immune system’s protective mechanisms. We also explore systems-level research into the regulatory and proteomic effects of SARS-CoV-2 infection and the immune response. Understanding the structure and behavior of the virus serves to contextualize the many facets of the COVID-19 pandemic and can influence efforts to control the virus and treat the disease. IMPORTANCE COVID-19 involves a number of organ systems and can present with a wide range of symptoms. From how the virus infects cells to how it spreads between people, the available research suggests that these patterns are very similar to those seen in the closely related viruses SARS-CoV-1 and possibly Middle East respiratory syndrome-related CoV (MERS-CoV). Understanding the pathogenesis of the SARS-CoV-2 virus also contextualizes how the different biological systems affected by COVID-19 connect. Exploring the structure, phylogeny, and pathogenesis of the virus therefore helps to guide interpretation of the broader impacts of the virus on the human body and on human populations. For this reason, an in-depth exploration of viral mechanisms is critical to a robust understanding of SARS-CoV-2 and, potentially, future emergent human CoVs (HCoVs).

PMID:34698547 | DOI:10.1128/mSystems.00095-21

J Comput Biol. 2021 Oct 25. doi: 10.1089/cmb.2021.0306. Online ahead of print.

ABSTRACT

This article presents a novel scalable character-based phylogeny algorithm for dense viral sequencing data called SPHERE (Scalable PHylogEny with REcurrent mutations). The algorithm is based on an evolutionary model where recurrent mutations are allowed, but backward mutations are prohibited. The algorithm creates rooted character-based phylogeny trees, wherein all leaves and internal nodes are labeled by observed taxa. We show that SPHERE phylogeny is more stable than Nextstrain’s, and that it accurately infers known transmission links from the early pandemic. SPHERE is a fast algorithm that can process >200,000 sequences in <2 hours, which offers a compact phylogenetic visualization of Global Initiative on Sharing All Influenza Data (GISAID).

PMID:34698524 | DOI:10.1089/cmb.2021.0306

Nurs Educ Perspect. 2021 Nov-Dec 01;42(6):371-373. doi: 10.1097/01.NEP.0000000000000786.

ABSTRACT

The purpose of this quasi-experimental study was to evaluate best strategies for teaching intimate partner violence (IPV) education in an undergraduate community health nursing course. Results suggest gaming was a more effective strategy than storytelling for knowledge acquisition and storytelling was more effective for knowledge retention. IPV-related nursing interventions can impact client outcomes; therefore, education is needed prior to entering the workforce. The evaluation of strategies to improve knowledge acquisition and retention of IPV content is essential to ensure best practices for detection and intervention.

PMID:34698473 | DOI:10.1097/01.NEP.0000000000000786

Diagn Cytopathol. 2021 Oct 26. doi: 10.1002/dc.24896. Online ahead of print.

ABSTRACT

BACKGROUND: Preserving the optimal quality of DNA and RNA is mandatory for molecular testing in lung adenocarcinoma cytological smears (LACSs).

METHODS: DNA and RNA were isolated from 90 frozen unstained and 46 May Grünwald Giemsa (MGG) stained LACSs prepared from bronchial washing (BW), bronchial brushing (BB), and pleural effusion (PE) samples during 3 years. Concentrations of nucleic acids in all LACSs were assessed by spectrophotometric analysis. Fragmentation of DNA and RNA was determined by PCR amplification of selected genes. Amplicons of 100, 200, 300, 400, and 600 bp were used for DNA and 108 bp-long HPRT1 transcript fragment for RNA fragmentation analysis.

RESULTS: Among 90 frozen LACSs, significantly lower DNA concentrations of BB and RNA concentrations of BW samples frozen for 6-10 months were observed in comparison with samples frozen for longer periods (p < .05). Among 46 paired LACSs, 44 (95.7%) frozen and 15 (32.6%) MGG-stained samples showed 600 bp-long DNA amplicons. Statistically significant difference (p < .05) in the fragmentation of DNA between frozen and MGG-stained LACSs was observed (p < .05), with DNA being less fragmented in frozen LACSs. In addition, 33 (71.7%) frozen and 36 (78.2%) MGG-stained LASCs showed HPRT1 gene amplicon of 108 bp. RNA was less fragmented in 3-year old MGG-stained samples than in LACSs frozen for 3 years.

CONCLUSION: DNA and RNA extracted from frozen and MGG-stained LACSs showed different results depending on the time of storage and/or type of samples, but in general all samples had adequate quantity and quality for downstream molecular testing.

PMID:34698443 | DOI:10.1002/dc.24896

Pediatr Transplant. 2021 Oct 26:e14158. doi: 10.1111/petr.14158. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of this study was to assess improvements in long-term survival of pediatric patients after liver transplantation by analyzing outcomes in transplant recipients who survived beyond 1 year after transplantation. There has been a marked increase in the 1-year survival of pediatric patients, from 78% in transplant recipients between 1987 and 1990 to 95% in transplant recipients between 2011 and 2017. The long-term outcomes have not seen a similar trend, creating a disparity that warrants analysis.

METHODS: We analyzed 13 753 pediatric patients who survived for 1 year after receiving orthotopic liver transplantation between 1987 and 2017. The study period was divided into six eras. Outcomes were analyzed using the Kaplan-Meier method for time-to-event analysis, and multivariable Cox regression.

RESULTS: There were no significant gains in long-term outcomes among 1-year survivors over the past three decades. Log-rank tests for equality of survivor functions between each era and 1987-1990 were not statistically significant. Cause of death analysis revealed that although infections caused 20.6% of deaths in patients transplanted between 1987 and 1990, this number dropped to 5.6% in those transplanted between 2011 and 2017 (p = .01). Malignancy caused 10.6% of deaths in 1987-1990 but caused 22.2% of the deaths in 2011-2017 (p = .04).

CONCLUSION: Despite the gratifying gains in short-term survival of pediatric patients, 1-year survivors have no significant improvements in long-term survival after undergoing a liver transplantation. Long-term sequelae of immunosuppression, such as malignancy and infection, continue to be the most common causes of death. This study highlights the necessity for better long-term management of immunosuppression.

PMID:34698432 | DOI:10.1111/petr.14158

Diabet Med. 2021 Oct 26:e14733. doi: 10.1111/dme.14733. Online ahead of print.

ABSTRACT

AIMS: This real-world observational clinical programme evaluated short and medium-term effects of intermittent flash glucose monitoring on HbA1c, glycaemic variability and lifestyle behavioural changes.

METHODS: Two first-generation Libre flash glucose monitoring sensors were provided 3-4 months apart with a food, activity diary, user evaluation survey and treatment modification after each sensor wear. T-tests were used to compare glucose variables within each sensor (week 1 vs. week 2) and between sensors (1^st sensor vs. 2^nd sensor). EasyGV software was used to calculate glycaemic variability.

RESULTS: From 42 type 1 diabetes and 120 type 2 diabetes participants, there was no statistically significant change in mean HbA1c for participants with type 1 diabetes at 3-4 months after the 1^st sensor but there was a statistically significant HbA1c reduction for participants with type 2 diabetes [-4 mmol/mol (-0.4%), p=0.008], despite no statistically significant differences in carbohydrate intake, exercise frequency and duration. Greater reduction was seen in those with baseline HbA1c> 86 mmol/mol (10%) in both type 1 [-12 mmol/mol (-1.1%), p=0.009] and type 2 diabetes [-11 mmol/mol (-1.0%), p=0.001). Both type 1 and type 2 diabetes showed improvements in Glucose Management Indicator and percentage time-above-range when comparing week 1 vs. week 2 of the same sensor. Higher scan frequency resulted in improved glycaemic parameters and certain measures of glycaemic variability. Majority of participants (85%) agreed that flash glucose monitoring is a useful device but only 60% were keen to use it for daily monitoring.

CONCLUSION: Constant feedback from flash glucose monitoring improves glycaemic parameters within the first week of wear. Intermittent use 3-4 months apart resulted in greater improvements for those with higher baseline HbA1c.

PMID:34698420 | DOI:10.1111/dme.14733

Prostate. 2021 Oct 26. doi: 10.1002/pros.24260. Online ahead of print.

ABSTRACT

BACKGROUND: The Gleason scoring system is the most widely used method to assess prostate adenocarcinoma pathology however interobserver variability is significant. Gleason score, PSA level, and clinical stage comprise the NCCN risk stratification that guides treatment decision making. Given the importance of an accurate Gleason score and wide interobserver variability, referral centers routinely review outside pathology at the time of consultation. We sought to address the impact a secondary pathology review had on radiation therapy treatment recommendations in men with prostate cancer at our institution.

METHODS: We retrospectively collected patient data on 342 patients seen at our institution from January 2012 to December 2018. Clinicopathologic data were used to subdivide patients into risk groups and available treatment options per NCCN criteria. Cases reviewed by our genitourinary pathologist (GUP) were compared with reports from outside pathologists. Inter-rater reliability between pathologists was assessed with weighted Cohen’s kappa statistic and agreement of treatment options was determined by McNemar’s exact tests.

RESULTS: GUP scored more cores positive in 16.47% of cases on secondary review. Primary Gleason score was changed in 12.28% of patients and secondary score in 26.02% of cases. Total Gleason score was different in 29.24% of cases, 19.01% were downgraded and 10.23% upgraded. The weighted kappa statistic was 0.759 (95% confidence interval [CI]: 0.711, 0.807). 18.77% of patients were assigned to a different NCCN risk group following secondary review. The weighted kappa statistic comparing NCCN risk stratification was 0.802 (95% CI: 0.754, 0.850). Secondary review influenced radiation therapy recommendations pertaining to brachytherapy boost and androgen deprivation therapy in men with high risk disease (χ² = 5.33, p = 0.0386; χ² = 8.05, p = 0.0072, respectively). Kappa statistic was found to be highest when GUP assessed high-risk disease versus all other categories (κ = 0.823, 95% CI: 0.750, 0.895).

CONCLUSIONS: We found nearly one in five men (18.7%) was assigned a different NCCN risk group and thus offered potentially different treatment options after a secondary pathology review at our institution. Given the inherent nature of prostate cancer and lung disease-specific survival associated with modern therapies, our study demonstrates the importance of a secondary pathology review and its potential impact on radiation therapy recommendations.

PMID:34698410 | DOI:10.1002/pros.24260

Allergy. 2021 Oct 26. doi: 10.1111/all.15152. Online ahead of print.

NO ABSTRACT

PMID:34698405 | DOI:10.1111/all.15152

J Med Virol. 2021 Oct 26. doi: 10.1002/jmv.27408. Online ahead of print.

ABSTRACT

The pro-inflammatory (Th1) cytokines namely IL-2, IL-6, IL-12, IFN-γ, TNF-α are vital in the clearance of HIV infection. This prospective cohort study aimed to evaluate the polymorphisms of Th1 cytokine genes and their corresponding plasma cytokine levels in HIV-1 positive and exposed uninfected (EU) infants born to HIV-1 positive mothers. CD4 count, viral load of HIV-1 positive mothers was done using commercially available reagents. Cytokine genotyping analysis and levels was done in 20 HIV-1 positive and 54 EU infants. The polymorphisms of Th1 cytokines were done using PCR-SSP method. Plasma cytokine levels estimated using Bio-Plex-Pro cytokine assay (BIO-RAD; USA).Results revealed treatment status of the mothers and viral load were the two confounding factors having significant effect on HIV status of the infant. TNF-α GG genotype is significantly higher in EU infants as compared to HIV-1 positive infants. GG genotype was associated with high TNF- α levels in HIV-1 positive infants but the difference was not statistically significant. HIV-1 positive infants with -IFN-γ (+874) TT genotype was significantly associated with high IFN-γ levels. To the best of our knowledge this is the first study reporting the role of Th1 cytokine gene polymorphisms and their corresponding plasma cytokine levels in HIV-1 positive and EU infants from India. This article is protected by copyright. All rights reserved.

PMID:34698402 | DOI:10.1002/jmv.27408

Acta Obstet Gynecol Scand. 2021 Oct 26. doi: 10.1111/aogs.14254. Online ahead of print.

ABSTRACT

INTRODUCTION: To determine the impact on preterm birth (PTB) of a history of large loop excision of the transformation zone (LLETZ)-alone compared with a history of previous preterm birth-alone (PPTB) or a history of both (LLETZ+PPTB). Secondary analyses were performed to evaluate the impact of antenatal interventions, depth of cervical excision, and patient risk factors on PTB rate in each cohort.

MATERIAL AND METHODS: A retrospective observational cohort study of women referred to a tertiary Antenatal Prematurity Prevention Clinic with a history of LLETZ, PPTB, or LLETZ+PPTB. Information was collated from routinely collected clinical data on patient demographics, previous obstetric history, LLETZ dimensions, antenatal investigations/interventions, and gestation at delivery.

RESULTS: A total of 1231 women with singleton pregnancies were included, 543 with history of LLETZ-alone, 607 with a history of PPTB-alone and 81 with a history of LLETZ+PPTB. PTB rates were 8.8% in the LLETZ-alone group, which mirrored the PTB rate in the local background obstetric population (8.9%) compared with 28.7% in the PPTB-alone and 37.0% in the LLETZ+PPTB cohorts. PTB rates were higher in LLETZ cohorts treated with antenatal intervention (cervical cerclage or progesterone pessary) and there was no evidence of an effect of intervention on risk of PTB in post-excision patients with identified shortened mid-trimester cervical length. Logistic regression modeling identified PPTB as a strong predictor of recurrent PTB. Excision depth was correlated with gestation at delivery in the LLETZ-alone group (r = -0.183, p < 0.01) although this only reached statistical significance at depths of 20 mm or more (odds ratio [OR] 3.40, 95% CI 1.04-1.11, p = 0.04). Depth of excision was not correlated with delivery gestation in the LLETZ+PPTB group (r = -0.031, p = 0.82).

CONCLUSIONS: PPTB has a greater impact on subsequent PTB risk compared with depth of cervical excisional treatment. The value and nature of antenatal interventions should be investigated in the post-excision population.

PMID:34698370 | DOI:10.1111/aogs.14254