Nevin Manimala

Sci Rep. 2021 Apr 15;11(1):8226. doi: 10.1038/s41598-021-87337-1.

ABSTRACT

Age-related macular degeneration (AMD) is a highly prevalent degenerative disease and a leading cause of vision loss worldwide. Evidence for an inflammatory component in the development of AMD exists, yet the exact mechanisms remain unclear. Bisretinoid N-retinylidene-N-retinylethanolamine (A2E) in retinal pigmental epithelial (RPE) cells, and in extracellular deposits constitutes a hallmark of AMD, but its role in the pathology of AMD is elusive. Here, we tested the hypothesis that A2E is responsible for the heightened inflammatory activity in AMD. To this end, we measured ex vivo mRNA expression of the cytokines TNF-α, IL-6, and IL-10 in whole blood samples after stimulation with A2E in a clinical sample of 27 patients with neovascular AMD and 24 patients with geographic atrophy secondary to AMD. Patients’ spouses (n = 30) were included as non-affected controls. After stimulation with A2E, no statistical differences were found in the median expression level of TNF-α, IL-6, IL-10 between the control group, and the neovascular AMD and the geographic atrophy group. Our findings do not support evidence for the hypothesis, that A2E per se contributes to heightened inflammatory activity in AMD.

PMID:33859228 | DOI:10.1038/s41598-021-87337-1

Sci Rep. 2021 Apr 15;11(1):8323. doi: 10.1038/s41598-021-86193-3.

ABSTRACT

In age-related macular degeneration (AMD) research, dark adaptation has been found to be a promising functional measurement. In more severe cases of AMD, dark adaptation cannot always be recorded within a maximum allowed time for the test (~ 20-30 min). These data are recorded either as censored data-points (data capped at the maximum test time) or as an estimated recovery time based on the trend observed from the data recorded within the maximum recording time. Therefore, dark adaptation data can have unusual attributes that may not be handled by standard statistical techniques. Here we show time-to-event analysis is a more powerful method for analysis of rod-intercept time data in measuring dark adaptation. For example, at 80% power (at α = 0.05) sample sizes were estimated to be 20 and 61 with uncapped (uncensored) and capped (censored) data using a standard t-test; these values improved to 12 and 38 when using the proposed time-to-event analysis. Our method can accommodate both skewed data and censored data points and offers the advantage of significantly reducing sample sizes when planning studies where this functional test is an outcome measure. The latter is important because designing trials and studies more efficiently equates to newer treatments likely being examined more efficiently.

PMID:33859209 | DOI:10.1038/s41598-021-86193-3

Nat Commun. 2021 Apr 15;12(1):2267. doi: 10.1038/s41467-021-22510-8.

ABSTRACT

Studies in humans and laboratory animals link stable gut microbiome “enterotypes” with long-term diet and host health. Understanding how this paradigm manifests in wild herbivores could provide a mechanistic explanation of the relationships between microbiome dynamics, changes in dietary resources, and outcomes for host health. We identify two putative enterotypes in the African buffalo gut microbiome. The enterotype prevalent under resource-abundant dietary regimes, regardless of environmental conditions, has high richness, low between- and within-host beta diversity, and enrichment of genus Ruminococcaceae-UCG-005. The second enterotype, prevalent under restricted dietary conditions, has reduced richness, elevated beta diversity, and enrichment of genus Solibacillus. Population-level gamma diversity is maintained during resource restriction by increased beta diversity between individuals, suggesting a mechanism for population-level microbiome resilience. We identify three pathogens associated with microbiome variation depending on host diet, indicating that nutritional background may impact microbiome-pathogen dynamics. Overall, this study reveals diet-driven enterotype plasticity, illustrates ecological processes that maintain microbiome diversity, and identifies potential associations between diet, enterotype, and disease.

PMID:33859184 | DOI:10.1038/s41467-021-22510-8

Rev Esp Salud Publica. 2021 Apr 16;95:e202104054.

ABSTRACT

OBJECTIVE: To face the COVID-19 pandemic, our intensive care and hospitalization units were expanded, surgical activity was limited to urgent and non-delayed procedures and teleconsultations were increased in order to minimize face-to-face consultations. The objective of this work was to learn users’ satisfaction with teleconsultations performed during the pandemic as well as its benefits, applications and areas for improvement.

METHODS: Cross-sectional study through a questionnaire with 26 closed questions and 5 open ones, grouped in 9 dimensions: patient characteristics; the query; treatment; utility; resolution; security; satisfaction; face-to-face modality and opportunities for improvement. Necessary sample size: 307 (confidence: 95%; error: 3%; expected satisfaction: 92%). Definitive sample: 352. Stratified random sampling by specialty. Period: March 16th-May 25th 2020. The statistical analysis was done with the statistical program SPSS vs.27.0. 95% confidence intervals were calculated.Statistical significance was established at p<0.05.

RESULTS: Patient profile: age 54 (SD: 18.6) years; 213 (60.5%) women. Calls made by doctors (298; 84.7%) and nurses (15; 4.3%); 342 (97.2%) attended at home. Reasons: follow-up (223; 63.4%); first consultation (45; 12.8%); result’s report (23; 6.5%) and manage an appointment (50; 14.2%). 29 (8.62%) were directed to another center. 335 (95.44%; 95% CI: 93.26%-97.62%) patients were satisfied and 309 (91.96%; 95% CI: 89.06%-94.87%) would recommend them. 351 (99.72%; 95% CI: 99.16%-99.99%) felt they were treated with kindness; 336 (95.96%; 95% CI: 93.81%-98.11%) considered sufficient care; 309 (95.96%; 95% CI: 93.81%-98.11%) were able to solve doubts; 311 (96.58%; 95% CI: 94.60%-98.57%) calmed down; for 245 (69.6%; 95% CI: 65.98%-74.67%) it was as useful as the face-to-face session; equally safe (240; 69.57%; 95% CI: 64.71%-74.42%) and beneficial (338; 96.02%; 95% CI: 94.25%-98.26%).

CONCLUSIONS: The high satisfaction expressed by users, the benefits verified and the high resolution of the teleconsultations, makes us consider expanding these services after the pandemic.

PMID:33859157

Otol Neurotol. 2021 Apr 14. doi: 10.1097/MAO.0000000000003128. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate local and systemic safety of bilateral iontophoretic administration of lidocaine with epinephrine or lidocaine alone to the tympanic membrane (TM).

STUDY DESIGN: A randomized, double-blind, two-arm study was conducted at a single center. Healthy adults were randomized to bilateral iontophoretic treatment with 2% lidocaine, 1:100,000 epinephrine, or 2% lidocaine (control). Otoscopy, cranial nerve examination, tympanometry, and audiometry safety evaluations were conducted before and 3-days post-procedure. Systemic safety was evaluated via analysis of vital signs taken before and up to 120 minutes post-iontophoresis, and blood samples collected before and up to 230 minutes post-iontophoresis.

RESULTS: Twenty-five subjects were treated with bilateral iontophoresis of either lidocaine and epinephrine (n = 15 subjects) or lidocaine alone (n = 10). Mean plasma epinephrine concentrations for both groups remained within the normal range for endogenous epinephrine. Mean plasma concentrations of lidocaine were not statistically different between groups, ranging from 0.245 to 2.28 ng/ml after administration of lidocaine with epinephrine (immediate post-iontophoresis to 230 min post-iontophoresis), compared with 1.35 to 2.14 ng/ml after administration of lidocaine alone. The presence of epinephrine slowed the systemic absorption of lidocaine. Lidocaine levels (Cmax 2.24 ng/ml) were approximately 2000-fold lower than the threshold for minor lidocaine toxicity. No device-, procedure- or drug-related adverse events were reported.

CONCLUSION: The local and systemic safety of bilateral iontophoretic delivery of 2% lidocaine, 1:100,000 epinephrine to the TM was demonstrated by low plasma levels of drug and absence of both serious and non-serious device-, procedure-, or drug-related adverse events.

PMID:33859140 | DOI:10.1097/MAO.0000000000003128

Otol Neurotol. 2021 Apr 14. doi: 10.1097/MAO.0000000000003177. Online ahead of print.

ABSTRACT

OBJECTIVES: Real-time electrocochleography (rt-ECochG) is a method to detect intracochlear potential changes during cochlear implantation (CI). Steep amplitude drops of the cochlear microphonic (CM) signal (so called “ECochG events”) have been correlated with worse residual hearing outcomes. However, the sensitivity and specificity of monitoring CM amplitude on its own are too low to use it as a biomarker. The aim of this article was to establish if additional signal components would help to better predict postoperative hearing outcomes.

DESIGN AND SETTING: Single-center, prospective cohort study at a tertiary referral hospital.

PARTICIPANTS AND INTERVENTIONS: Between 2017 and 2020, we included 73 adult patients receiving a lateral wall cochlear implant electrode. During electrode insertion, rt-ECochG measurements were performed.

MAIN OUTCOMES: We calculated a multiple regression analysis for patients with one ECochG event. The dependant variable was the relative acoustic hearing result 4 weeks after surgery. Independent variables were CM latency, a ratio of the auditory nerve neurophonic to the CM (the ANN/CM index) as well as CM signal recovery.

RESULTS: The change of the ANN/CM index linearly correlated with acoustic hearing outcomes 4 weeks after surgery. Adding this factor led to a statistically significant increase in the variance accounted for by the regression model.

CONCLUSIONS: When monitoring the implantation process with rt-ECochG, prediction of postoperative hearing thresholds is improved by addition of the ANN/CM index to a model that includes CM amplitude fluctuation.

PMID:33859138 | DOI:10.1097/MAO.0000000000003177

J Dev Behav Pediatr. 2021 Apr 13. doi: 10.1097/DBP.0000000000000951. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aims to characterize the association between maternal pregnancy intention and socioemotional developmental outcomes in a Brazilian sample of preschool-aged children.

METHODS: Data from children aged 4 to 5 years and their primary caregivers in Embu das Artes, a Brazilian municipality in the state of São Paulo, were collected in 2016. Maternal pregnancy intention was defined as intended or unintended, which was then further stratified as mistimed or unwanted. Outcomes included socioemotional developmental delay, internalizing and externalizing behaviors, and school readiness. We estimated risk ratios (RRs) for unadjusted and inverse-probability-weighted regression adjustment (IPWRA) analyses using 2-level (intended vs unintended) and 3-level (intended vs mistimed vs unwanted) exposure definitions.

RESULTS: Of 1,034 total mothers, 40.7% reported their pregnancy as intended, 46.0% as mistimed, and 13.4% as unwanted. In both unadjusted and IPWRA analyses comparing intended and unintended pregnancies, all associations failed to reach statistical significance. In the IPWRA analysis using the 3-level exposure definition, unwanted pregnancies were associated with higher risk of socioemotional developmental delay (RR = 1.14; 95% confidence interval [CI], 1.01-1.28) and co-occurring internalizing and externalizing behaviors (RR = 1.11, 95% CI, 1.00-1.22), compared with intended pregnancies.

CONCLUSION: There was higher risk of poor child outcomes among unwanted compared with intended pregnancies, whereas mistimed pregnancies were not associated with poor outcomes. Further research using standardized definitions of pregnancy intention along with targeted interventions that increase access to family planning services and counseling for parents of children born after unintended pregnancies is needed.

PMID:33859123 | DOI:10.1097/DBP.0000000000000951

AIDS. 2021 Apr 15. doi: 10.1097/QAD.0000000000002920. Online ahead of print.

ABSTRACT

BACKGROUND: HIV and HCV have each been linked with cardiac dysfunction. Studies of HIV have often lacked appropriate controls and primarily involved men, while data for HCV are sparse.

METHODS: We performed repeat echocardiography over a median interval of 12 years in participants from the Women’s Interagency HIV Study in order to evaluate the relationships of HIV and HCV with incident left ventricular (LV) dysfunction (systolic or diastolic).

RESULTS: Of the 311 women included (age 39 ± 9), 70% were HIV and 20% HCV positive. Forty three participants (13.8%) developed LV dysfunction, of which 79.1% was diastolic. Compared to participants with neither infection, the group with HIV-HCV coinfection showed a significantly increased risk of incident LV dysfunction after adjustment for risk factors (RR = 2.96 [95% CI = 1.05-8.31]), but associations for the HCV monoinfected and HIV monoinfected groups were not statistically significant (RR = 2.54 [0.83-7.73] and RR = 1.66 [0.65-4.25], respectively). Comparison of HCV-positive and HCV-negative women showed a significantly increased risk independent of covariates (RR = 1.96 [1.02-3.77]), but this was not the case for HIV-positive vs. HIV-negative women (RR = 1.43 [0.76-2.69]). There was no evidence of HCV-by-HIV interaction. A more restrictive definition of LV diastolic dysfunction led to fewer incident cases, but a similar, though non-significant, risk estimate for HCV.

CONCLUSIONS: Among middle-aged women, HCV but not HIV infection was associated with a pronounced risk of incident LV dysfunction. Although the influence of residual confounding cannot be excluded, these findings bolster the potential benefits that could be realized by adopting recent recommendations for expanding HCV screening and treatment.

PMID:33859109 | DOI:10.1097/QAD.0000000000002920

J Nurses Prof Dev. 2021 Apr 12. doi: 10.1097/NND.0000000000000740. Online ahead of print.

ABSTRACT

This study identified nurse preceptor role frequency to newly licensed registered nurses and how it made a difference to the preceptors’ job satisfaction. Statistical analysis revealed there was no difference in job satisfaction in preceptors who performed in the role one to four times than those who served five times or more, F(4, 124) = 0.261, p > .05. The study found variation in preceptor role preparation and differing registered nurse practice experience prior to performing as a preceptor.

PMID:33859098 | DOI:10.1097/NND.0000000000000740

Am J Dermatopathol. 2021 Apr 13. doi: 10.1097/DAD.0000000000001953. Online ahead of print.

ABSTRACT

Cutaneous malignant melanoma is an aggressive cancer that contributes significantly to cancer-related mortality. Over the years, a deeper scrutiny of melanoma biology has led to identification of diverse evolutionary patterns involving various genetic pathways. This study attempts to further understand the genetic landscape of cutaneous malignant melanoma in terms of loco-regional variations and malignant potential. Thirty-five cases of cutaneous malignant melanoma were retrieved from the archives and were classified based on location of the primary tumor and presence or absence of metastatic disease. Next-generation sequencing data consisting of base substitutions, copy number variations, indels, and rearrangements in a total of 324 genes were analyzed for recurrent genetic alterations. Statistical analysis was performed using IBM SPSS26 software. Mutations in KDM gene family were found in 62.5% of the melanomas in the head and neck as compared with 10% in melanomas of the extremity and trunk (P = 0.03). Mutations in the RAS gene family were found in 70% of melanomas in the extremities as compared to 12.5% in melanomas of the head and neck (P = 0.003). BTK gene mutations were found exclusively in melanomas of the head and neck (P = 0.032). CREBBP mutations were seen in 50% of the nonmetastatic melanomas as compared with 3.57% of metastatic melanomas (P = 0.005). This study highlights the loco-regional variations in cutaneous malignant melanoma for genetic alterations involving the KDM, RAS, and BTK gene family. In addition, the CREBBP mutational status is identified as a potential prognostic marker for predicting metastatic potential in cutaneous malignant melanomas.

PMID:33859081 | DOI:10.1097/DAD.0000000000001953