Nevin Manimala

Photodiagnosis Photodyn Ther. 2021 Oct 3:102569. doi: 10.1016/j.pdpdt.2021.102569. Online ahead of print.

ABSTRACT

PURPOSE: To determine the effect of angiotensin-converting enzyme (ACE) inhibitors on choroidal vascularity using the binarization method in a group of treatment-naïve hypertensive patients.

METHODS: There were 48 treatment-naive hypertensive patients who were diagnosed according to the “2013 European Society of Hypertension/European Society of Cardiology” guideline and started angiotensin-converting enzyme inhibitor perindopril (Coversyl) in the study. As a control group, 48 healthy volunteers were randomly selected among people who attended the outpatient clinic for routine ophthalmological examination. Enhanced-depth imaging optical coherence tomography (EDI-OCT) images were captured at baseline and at 1 month after treatment. Binarization of the EDI-OCT images was performed by Image-J software. The choroidal thickness (CT), total choroidal area, luminal area, stromal area, and choroidal vascularity index (CVI) were measured.

RESULTS: There was a statistically significant increase in CT at all locations (subfoveal, nasal, and temporal) at 1 month after treatment compared with baseline (for all, p˂0.001). Choroidal structural parameters and the mean CVI were statistically significantly increased at 1 month after treatment (for all, p˂0.001). When compared, there was no statistically significant difference for the vascular parameters between the control group and the patient group at 1 month (for all, p>0.05).

CONLUSION: A statistically significant improvement was demonstrated in the choroidal vascular parameters except for the stromal area after treating with an ACE inhibitor in a group of hypertensive patients.

PMID:34614428 | DOI:10.1016/j.pdpdt.2021.102569

N Engl J Med. 2021 Oct 6. doi: 10.1056/NEJMoa2114114. Online ahead of print.

ABSTRACT

BACKGROUND: Waning of vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (Covid-19) is a concern. The persistence of BNT162b2 (Pfizer-BioNTech) vaccine effectiveness against infection and disease in Qatar, where the B.1.351 (or beta) and B.1.617.2 (or delta) variants have dominated incidence and polymerase-chain-reaction testing is done on a mass scale, is unclear.

METHODS: We used a matched test-negative, case-control study design to estimate vaccine effectiveness against any SARS-CoV-2 infection and against any severe, critical, or fatal case of Covid-19, from January 1 to September 5, 2021.

RESULTS: Estimated BNT162b2 effectiveness against any SARS-CoV-2 infection was negligible in the first 2 weeks after the first dose. It increased to 36.8% (95% confidence interval [CI], 33.2 to 40.2) in the third week after the first dose and reached its peak at 77.5% (95% CI, 76.4 to 78.6) in the first month after the second dose. Effectiveness declined gradually thereafter, with the decline accelerating after the fourth month to reach approximately 20% in months 5 through 7 after the second dose. Effectiveness against symptomatic infection was higher than effectiveness against asymptomatic infection but waned similarly. Variant-specific effectiveness waned in the same pattern. Effectiveness against any severe, critical, or fatal case of Covid-19 increased rapidly to 66.1% (95% CI, 56.8 to 73.5) by the third week after the first dose and reached 96% or higher in the first 2 months after the second dose; effectiveness persisted at approximately this level for 6 months.

CONCLUSIONS: BNT162b2-induced protection against SARS-COV-2 infection appeared to wane rapidly following its peak after the second dose, but protection against hospitalization and death persisted at a robust level for 6 months after the second dose. (Funded by Weill Cornell Medicine-Qatar and others.).

PMID:34614327 | DOI:10.1056/NEJMoa2114114

J Hepatobiliary Pancreat Sci. 2021 Oct 6. doi: 10.1002/jhbp.1054. Online ahead of print.

ABSTRACT

BACKGROUND: The prognostic implication of mutant KRAS (mKRAS) among patients with primary disease in the rectum remains unknown.

METHODS: From 2000 to 2018, patients undergoing hepatectomy for colorectal liver metastases at 10 collaborating international institutions with documented KRAS status were surveyed.

RESULTS: A total of 834 (65.8%) patients with primary colon cancer and 434 (34.2%) patients with primary rectal cancer were included. In patients with primary colon cancer, mKRAS served as a reliable prognostic biomarker of poor overall survival (OS) (hazard ratio (HR): 1.58, 95%CI 1.28-1.95) in the multivariable analysis. Although a trend towards significance was noted, mKRAS was not found to be an independent predictor of OS in patients with primary rectal tumors (HR 1.34, 95%CI 0.98-1.80). For colon cancer, the specific codon impacted in mKRAS appears to reflect underlying disease biology and oncologic outcomes, with codon 13 being associated with particularly poor OS in patients with left-sided tumors (codon 12, HR 1.56, 95%CI 1.22-1.99; codon 13, HR 2.10 95%CI 1.43-3.08;). Stratifying the rectal patient population by codon mutation did not confer prognostic significance following hepatectomy.

CONCLUSIONS: While the left-sided colonic disease is frequently grouped with rectal disease, our analysis suggests that there exist fundamental biologic differences that drive disparate outcomes. Although there was a trend toward significance of KRAS mutations for patients with primary rectal cancers, it failed to achieve statistical significance.

PMID:34614304 | DOI:10.1002/jhbp.1054

Mol Ecol. 2021 Oct 6. doi: 10.1111/mec.16211. Online ahead of print.

ABSTRACT

The natural host ranges of many viruses are restricted to very specific taxa. Little is known about the molecular barriers between species that lead to the establishment of this restriction or generally prevent virus emergence in new hosts. Here, we identify genomic polymorphisms in a natural rodent host associated with a strong genetic barrier to the transmission of European Tula orthohantavirus (TULV). We analyzed the very abrupt spatial transition between two major phylogenetic clades in TULV across the comparatively much wider natural hybrid zone between evolutionary lineages of their reservoir host, the common vole (Microtus arvalis). Genomic scans of 79 225 Single Nucleotide Polymorphisms (SNPs) in 323 TULV infected host individuals detected 30 SNPs that were consistently associated with the TULV clades CEN.S or EST.S in two replicate sampling transects. Focusing the analysis on 199 voles with evidence of genomic admixture at the individual level (0.1 – 0.9) supported statistical significance for all 30 loci. Host genomic variation at these SNPs explained up to 37.6% of clade-specific TULV infections. Genes in the vicinity of associated SNPs include SAHH, ITCH and two members of the Syngr gene family, which are involved in functions related to immune response or membrane transport. This study demonstrates the relevance of natural hybrid zones as systems not only for studying processes of evolutionary divergence and speciation, but also for the detection of evolving genetic barriers for specialized parasites.

PMID:34614264 | DOI:10.1111/mec.16211

Mol Ecol. 2021 Oct 6. doi: 10.1111/mec.16213. Online ahead of print.

ABSTRACT

Unisexual vertebrates typically form through hybridization events between sexual species in which reproductive mode transitions occur in the hybrid offspring. This evolutionary history is thought to have important consequences for the ecology of unisexual lineages and their interactions with congeners in natural communities. However, these consequences have proven challenging to study owing to uncertainty about patterns of population genetic diversity in unisexual lineages. Of particular interest is resolving the contribution of historical hybridization events vs. postformational mutation to patterns of genetic diversity in nature. Here we use restriction site associated DNA genotyping to evaluate genetic diversity and demographic history in Aspidoscelis laredoensis, a diploid unisexual lizard species from the vicinity of the Rio Grande River in southern Texas and northern Mexico. The sexual progenitor species from which one or more lineages are derived also occur in the Rio Grande Valley region, although patterns of distribution across individual sites are quite variable. Results from population genetic and phylogenetic analyses resolved the major axes of genetic variation in this species and highlight how these match predictions based on historical patterns of hybridization. We also found discordance between results of demographic modelling using different statistical approaches with the genomic data. We discuss these insights within the context of the ecological and evolutionary mechanisms that generate and maintain lineage diversity in unisexual species. As one of the most dynamic, intriguing, and geographically well investigated groups of whiptail lizards, these species hold substantial promise for future studies on the constraints of diversification in unisexual vertebrates.

PMID:34614250 | DOI:10.1111/mec.16213

Int Endod J. 2021 Oct 6. doi: 10.1111/iej.13638. Online ahead of print.

ABSTRACT

AIM: To investigate the influence of strain differences in immune responses on the pathogenesis of experimental periapical lesions in Dark Agouti (DA) and Albino Oxford (AO) inbred strains of rats.

METHODOLOGY: Periapical lesions were induced in male DA and AO rats by pulp exposure of the first mandibular right molars to the oral environment. Animals were sacrificed 21 days after pulp exposure. The mandibular jaws were retrieved and prepared for radiographic, pathohistological, immunohistochemical analysis, real-time PCR, and flow cytometry. Blood samples and the supernatant of periapical lesions were collected for measurement of cytokines and oxidative stress marker levels. Statistical analysis was performed the Kruskal-Wallis H and Mann-Whitney U non-parametric tests or parametric One-Way ANOVA and Independent Samples T-test to determine the differences between groups depending on the normality of the data. A significant difference was considered when p values were < .05.

RESULTS: DA rats developed significantly larger (p˂.05) periapical lesions compared to AO rats as confirmed by radiographic and pathohistological analysis. The immunohistochemical staining intensity for CD3 was significantly higher in periapical lesions of DA rats compared to AO rats (p˂.05). In DA rats, periapical lesions had a significantly higher (p˂.05) percentage of CD3+ cells compared to AO rats. Also, the percentage of INF-γ, IL-17, and IL-10 CD3+CD4+ cells was significantly higher in DA rats (p˂.05). DA rats had a significantly higher Th17/Th10 ratio. RT-PCR expression of IL-1β, INF-γ, and IL-17 genes was significantly higher in periapical lesions of DA compared to AO rats (p˂.05). The receptor activator of nuclear factor kappa-Β ligand/osteoprotegerin ratio was higher in DA compared to AO rats with periapical lesions (p˂.05). Systemic levels of TNF-α and IL-6 were significantly higher in DA compared to AO rats (p˂.05). Levels of lipid peroxidation measured as thiobarbituric acid reactive substances and reduced glutathione were significantly higher (p˂.05) in the supernatant in the periapical lesions of DA rats.

CONCLUSION: After pulp exposure, Dark Agouti rats developed much larger periapical lesions compared to Albino Oxford rats. Genetically determined differences in immunopathology have been demonstrated to be a significant element defining the severity of periapical lesions.

PMID:34614243 | DOI:10.1111/iej.13638

JPEN J Parenter Enteral Nutr. 2021 Oct 6. doi: 10.1002/jpen.2272. Online ahead of print.

ABSTRACT

BACKGROUND: The glucagon-like peptide 2 (GLP-2) analogue teduglutide is an effective drug for the treatment of patients suffering from short bowel syndrome with intestinal failure (SBS-IF). This intestinotrophic peptide improves intestinal capacity for fluid and nutrient absorption through induction of mucosal growth and reduction of gastrointestinal motility. Clinical trials demonstrated the efficacy of teduglutide in reducing the need for parenteral support. This study describes an SBS-IF patient population receiving teduglutide therapy in a specialized medical care setting.

METHOD: A retrospective analysis was performed using data of patients suffering from non-malignant SBS-IF. They were treated with teduglutide in a multidisciplinary SBS-IF program at a single university medical center between June 2016 and June 2020.

RESULTS: Thirteen patients were treated with teduglutide and included into the final analysis. Mean small bowel length was 82±31cm with 77% of patients having their colon in continuity. Over a median follow-up period of 107 weeks, all patients (13/13, 100%) responded to the therapy with a clinically significant reduction of parenteral support volume. Mean parenteral support reduction increased with therapy duration and ranged from -82.5% at week 24 (n = 13) to -100% in patients (n = 5) who were treated for 144 weeks. Enteral autonomy was achieved in 12/13 (92%). Teduglutide therapy also improved stool frequency and consistency, changed dietary habits and reduced disease-associated sleep disruptions.

CONCLUSION: Integrating SBS-IF patients treated with teduglutide in a pro-active and tight-meshed patient care program significantly improves the clinical outcome leading to an increased proportion of patients who reach enteral autonomy. This article is protected by copyright. All rights reserved.

PMID:34614239 | DOI:10.1002/jpen.2272

Public Health Nurs. 2021 Oct 6. doi: 10.1111/phn.12978. Online ahead of print.

ABSTRACT

BACKGROUND: The COVID-19 pandemic has highlighted the importance of a strong, effective public health nursing workforce while also requiring public health nursing faculty to adapt teaching strategies as courses transitioned online. It is essential to understand how the pandemic-enforced transition from face-to-face to remote learning impacts student outcomes. The purpose of this paper is to compare student learning outcomes in a pre-licensure public health nursing course before, during, and after the transition to remote learning.

METHODS: Descriptive statistics were computed for assignments, exams, and final course grades for three terms (Fall 2019, Spring 2020 and Fall 2020).

RESULTS: Analysis showed statistically significant differences between terms for assignments and exams but not the final course grade. However, these differences were driven by small standard deviations rather than differences between mean scores demonstrating that there was actual little difference in student learning outcomes across terms.

CONCLUSIONS: Authors suggest strategies to support consistent academic outcomes and future research needed understand student learning outcomes during the pandemic; ultimately building the public health nursing workforce necessary to address the current and future public health crises.

PMID:34614222 | DOI:10.1111/phn.12978

J Community Psychol. 2021 Oct 6. doi: 10.1002/jcop.22727. Online ahead of print.

ABSTRACT

Helminthiasis causes iron deficiency anemia, pica, growth, and mental retardation in children. Deworming exercises are being included as part of various interventional programs to reduce the disease burden. However, the success or failure of such activities in terms of household caregivers’ knowledge and practice of deworming is not usually adequately evaluated, thus this study. This was a cross-sectional descriptive study carried out in the rural community of Enugu State, Nigeria. Pretested semi-structured interviewer-administered questionnaire was used. Inferential statistics, χ² test, and t-test were also used in the analysis for categorical and continuous variables, respectively. A total of 294 preschool children and 250 caregivers were studied. Among the caregivers, 212 (71.9%) had good knowledge and 149 (50.5%) had good practice of deworming. There was a statistically significant association between the age of respondents and knowledge score (χ² = 6.471, p = 0.039) and between the educational level of respondents and practice score (χ² = 30.632, p < 0.001). Most respondents in the rural community had a good knowledge of worm infestation and only half had good practice of deworming. Also, there was a significant difference between the age of respondents and knowledge of helminthiasis and between the educational level of respondents and deworming activities of respondents.

PMID:34614217 | DOI:10.1002/jcop.22727

Cancer. 2021 Oct 6. doi: 10.1002/cncr.33939. Online ahead of print.

ABSTRACT

BACKGROUND: TAILORx (Trial Assigning Individualized Options for Treatment) prospectively assessed fatigue and endocrine symptoms among women with early-stage hormone receptor-positive breast cancer and a midrange risk of recurrence who were randomized to endocrine therapy (E) or chemotherapy followed by endocrine therapy (CT+E).

METHODS: Participants completed the Functional Assessment of Chronic Illness Therapy-Fatigue, the Patient-Reported Outcomes Measurement Information System-Fatigue Short Form, and the Functional Assessment of Cancer Therapy-Endocrine Symptoms at the baseline and at 3, 6, 12, 24, and 36 months. Linear regression was used to model outcomes on baseline symptoms, treatment, and other factors.

RESULTS: Participants (n = 458) in both treatment arms reported greater fatigue and endocrine symptoms at early follow-up in comparison with the baseline. The magnitude of change in fatigue was significantly greater for the CT+E arm than the E arm at 3 and 6 months but not at 12, 24, or 36 months. The CT+E arm reported significantly greater changes in endocrine symptoms from the baseline to 3 months in comparison with the E arm; change scores were not significantly different at later time points. Endocrine symptom trajectories by treatment differed by menopausal status, with the effect larger and increasing for postmenopausal patients.

CONCLUSIONS: Adjuvant CT+E was associated with greater increases in fatigue and endocrine symptoms at early time points in comparison with E. These differences lessened over time, and this demonstrated early chemotherapy effects more than long-term ones. Treatment arm differences in endocrine symptoms were more evident in postmenopausal patients.

LAY SUMMARY: Participants in TAILORx (Trial Assigning Individualized Options for Treatment) with early-stage hormone receptor-positive breast cancer and an intermediate risk of recurrence were randomly assigned to endocrine or chemoendocrine therapy. Four hundred fifty-eight women reported fatigue and endocrine symptoms at the baseline and at 3, 6, 12, 24, and 36 months. Both groups reported greater symptoms at early follow-up versus the baseline. Increases in fatigue were greater for the chemoendocrine group than the endocrine group at 3 and 6 months but not later. The chemoendocrine group reported greater changes in endocrine symptoms in comparison with the endocrine group at 3 months but not later.

PMID:34614209 | DOI:10.1002/cncr.33939