Category: Nevin Manimala

Inorg Chem. 2023 Feb 23. doi: 10.1021/acs.inorgchem.2c04430. Online ahead of print.

ABSTRACT

The two new ternary amalgams K_1-xRb_xHg₁₁ [x = 0.472(7)] and Cs_3-xCa_xHg₂₀ [x = 0.20(3)] represent two different examples of how to create ternary compounds from binaries by statistical atom substitution. K_1-xRb_xHg₁₁ is a Vegard-type mixed crystal of the isostructural binaries KHg₁₁ and RbHg₁₁ [cubic, BaHg₁₁ structure type, space group Pm3̅m, a = 9.69143(3) Å, Rietveld refinement], whereas Cs_3-xCa_xHg₂₀ is a substitution variant of the Rb₃Hg₂₀ structure type [cubic, space group Pm3̅n, a = 10.89553(14) Å, Rietveld refinement] for which a fully substituted isostructural binary Ca phase is unknown. In K_1-xRb_xHg₁₁, the valence electron concentration (VEC) is not changed by the substitution, whereas in Cs_3-xCa_xHg₂₀, the VEC increases with the Ca content. Amalgams of electropositive metals form polar metal bonds and show “bad metal” properties. By thermal analysis, magnetic susceptibility and resistivity measurements, and density functional theory calculations of the electronic structures, we investigate the effect of the structural disorder introduced by creating mixed-atom occupation on the physical properties of the two new polar amalgam systems.

PMID:36821862 | DOI:10.1021/acs.inorgchem.2c04430

J Pediatr Gastroenterol Nutr. 2023 Feb 24:e003749. doi: 10.1097/MPG.0000000000003749. Online ahead of print.

ABSTRACT

OBJECTIVES: Pediatric patients undergoing esophagogastroduodenoscopy (EGD) commonly receive procedural sedation for comfort and to facilitate the procedure. EGD with procedural sedation carries the risk of several airway incidents and/or adverse events (AIAE). Topical pharyngeal anesthetics can blunt the airway reflexes and decrease the incidence of laryngospasm but has not been well studied with EGD under procedural sedation. We aimed to study the effect of adding a topical pharyngeal anesthetic (TPA) to propofol-based sedation on the rate of AIAE.

METHODS: This is a single-center, retrospective, observational cohort study. We compare AIAE rates (coughing, gagging, apnea, airway obstruction and laryngospasm) in children who received TPA as part of their propofol-based procedural sedation for EGD with those who did not receive TPA.

RESULTS: In 2021, 73 patients received TPA as part of the procedural sedation for EGD and 123 did not. The overall rate of AIAE was high with seventy-five (38%) patients experiencing one or more AIAE. Patients who received benzocaine spray experienced more AIAE than the control group [adjusted OR=1.16; 95% CI (1.01-1.34); p=0.037]. Coughing, gagging, apnea with desaturation rates and laryngospasm were similar in both groups [coughing adjusted OR=1.01; 95% CI (0.91-1.13); p=0.814] [gagging adjusted OR=1.01; 95% CI (0.91-1.13); p=0.814] [apnea adjusted OR=0.99; 95% CI (0.95-1.04); p=0.688] [laryngospasm OR=1.01; 95% CI (0.95-1.07); p=0.71]. The rate of airway obstruction requiring jaw thrust was higher in the benzocaine group but did not reach statistical significance [adjusted OR=1.11; 95% CI (0.97-1.26); p=0.133].

CONCLUSION: The use of topical pharyngeal benzocaine in children undergoing EGD with propofol-based sedation is associated with a higher overall AIAE rate. Most of the AIAE were mild incidents and only seven patients experienced true adverse events.

PMID:36821854 | DOI:10.1097/MPG.0000000000003749

Otolaryngol Head Neck Surg. 2023 Feb 23. doi: 10.1002/ohn.307. Online ahead of print.

ABSTRACT

OBJECTIVE: Assessing whether the additional use of narrow-band imaging (NBI) in transoral laser surgery (TOLS) for early laryngeal cancer improves clinical outcomes.

STUDY DESIGN: Randomized controlled trial, performed between September 2015 and November 2022.

SETTING: A tertiary referral hospital in The Netherlands.

METHODS: TOLS was carried out in 113 patients. The procedure was performed with white light imaging (WLI, n = 56) alone, or combined with NBI (n = 57). Patients received frequent follow-up laryngoscopy. Resection margin status, recurrence rate, and recurrence-free survival at 12 months, 18 months, and after study termination (maximum 86 months) were analyzed.

RESULTS: Thirty-one cases in the WLI group had a positive resection margin, versus 16 in the NBI group (p = .002). After 12 months, the recurrence-free survival was 92%: 87% for WLI versus 96% for NBI, p = .07. The recurrence rate was 7/56 (13%) for WLI, versus 2/57 (4%) for NBI, p = .09. After 18 months, the recurrence-free survival was 84% for WLI versus 96% for NBI, p = .02. The recurrence rate was 9/56 (16%) for WLI, versus 2/57 (4%) for NBI, p = .02. After study termination, the recurrence-free survival was 71% for WLI versus 83% for the NBI group (p = .08). The recurrence rate was 16/56 for WLI, versus 10/57 for NBI (p = .16).

CONCLUSION: The additional use of NBI during TOLS significantly decreased the number of positive resection margins. Although not statistically significant at all time points, patients treated with NBI-supported TOLS showed a lower recurrence rate and better recurrence-free survival. Further studies in larger patient groups are needed to confirm these results.

PMID:36821814 | DOI:10.1002/ohn.307

JCO Glob Oncol. 2023 Feb;9:e2200331. doi: 10.1200/GO.22.00331.

ABSTRACT

PURPOSE: The COVID-19 pandemic has affected public health worldwide. The efficacy and safety of COVID-19 vaccines have been evaluated in the general population; however, data on patients with malignancies are limited.

METHODS: This prospective longitudinal observational cohort study was conducted between June and July 2021. Enrolled adult patients with cancer were divided into chemotherapy and nonchemotherapy groups. All participants were immunized with two doses of the ChAdOx1 nCoV-19 or CoronaVac COVID-19 vaccines. The primary outcome was a comparison of the immunogenicity (as assessed by spike protein [anti-S] immunoglobulin G [IgG] antibody titers) of two doses of COVID-19 vaccine in the chemotherapy and nonchemotherapy groups. The secondary outcomes included the anti-S IgG seroconversion rate and vaccine safety in both groups.

RESULTS: Among the 173 enrolled patients with solid cancer, after COVID-19 vaccination, the chemotherapy group had a significantly lower median anti-S IgG titer than the nonchemotherapy group (26 v 237 U/mL, P < .001). A statistically significant difference in anti-S IgG titer was found between groups vaccinated with CoronaVac (7 v 90 U/mL, P < .001), but no difference was found in those vaccinated with ChAdOx1 nCoV-19 (818 v 1061 U/mL, P = .075). The anti-S IgG seroconversion rate was significantly lower in the chemotherapy group than that in the nonchemotherapy group (78.9% v 96.5%, P = .001). No new or serious vaccine-related adverse events were reported.

CONCLUSION: Patients with solid cancer receiving a COVID-19 vaccine while undergoing chemotherapy had lower immunogenicity responses to vaccination than those who were vaccinated while undergoing nonchemotherapy treatment. No statistically significant difference was observed in the COVID-19 vaccine safety profiles between groups.

PMID:36821802 | DOI:10.1200/GO.22.00331

Otolaryngol Head Neck Surg. 2023 Feb 23. doi: 10.1002/ohn.166. Online ahead of print.

ABSTRACT

The aim of this study was to prospectively evaluate the olfactory function in a series of individuals infected with SARS-CoV-2 and who had undergone psychophysical olfactory assessment prior to infection. Individuals unexposed to SARS-CoV-2 infection underwent a psychophysical evaluation of smell with the Sniffin’ Sticks test. The subjects were followed prospectively and included in the study if they developed SARS-CoV-2 infection with a second test 60 days after recovery. At the 60-day follow-up of the 41 included subjects, 2 (4.9%) self-reported persistent olfactory dysfunction (OD). The differences between TDI scores before and after infection were statistically significant (37 [interquartile range (IQR), 34.25-39.25] vs 34.75 [IQR, 32.25-38]; p = .021). Analyzing the individual olfactory domains, the differences were significant for threshold (T) (9.75 [IQR, 9-11.25] vs 8.25 [IQR, 7.25-10.25]; p = .009) but not for odor discrimination (D) (p = .443) and identification (I) (p = .159). SARS-CoV-2 causes a significant reduction in the olfactory function, in particular affecting the olfactory threshold, even in subjects who do not self-report an OD.

PMID:36821798 | DOI:10.1002/ohn.166

Genet Epidemiol. 2023 Feb 23. doi: 10.1002/gepi.22521. Online ahead of print.

ABSTRACT

Polygenic risk scores (PRS) quantify the genetic liability to disease and are calculated using an individual’s genotype profile and disease-specific genome-wide association study (GWAS) summary statistics. Type 1 (T1D) and type 2 (T2D) diabetes both are determined in part by genetic loci. Correctly differentiating between types of diabetes is crucial for accurate diagnosis and treatment. PRS have the potential to address possible misclassification of T1D and T2D. Here we evaluated PRS models for T1D and T2D in European genetic ancestry participants from the UK Biobank (UKB) and then in the Michigan Genomics Initiative (MGI). Specifically, we investigated the utility of T1D and T2D PRS to discriminate between T1D, T2D, and controls in unrelated UKB individuals of European ancestry. We derived PRS models using external non-UKB GWAS. The T1D PRS model with the best discrimination between T1D cases and controls (area under the receiver operator curve [AUC] = 0.805) also yielded the best discrimination of T1D from T2D cases in the UKB (AUC = 0.792) and separation in MGI (AUC = 0.686). In contrast, the best T2D model did not discriminate between T1D and T2D cases (AUC = 0.527). Our analysis suggests that a T1D PRS model based on independent single nucleotide polymorphisms may help differentiate between T1D, T2D, and controls in individuals of European genetic ancestry.

PMID:36821788 | DOI:10.1002/gepi.22521

Prim Care Companion CNS Disord. 2023 Feb 14;25(1):22m03267. doi: 10.4088/PCC.22m03267.

ABSTRACT

Objective: Improvement of cognitive function in patients with major depressive disorder (MDD) is an important treatment outcome. REL-1017 (esmethadone HCl) is a novel N-methyl-d-aspartate receptor (NMDAR) channel blocker and a potentially rapidly acting antidepressant. The objective of this study was to define the effects of REL-1017 on subjective cognitive measures in patients with MDD.

Methods: Post hoc analysis was conducted of subjective cognitive measures from the Montgomery-Asberg Depression Rating Scale (MADRS) and the Symptoms of Depression Questionnaire (SDQ) from a randomized, double-blind, placebo-controlled, Phase 2a study. The study, designed to assess the safety, tolerability, and efficacy of 2 dosages (25 mg and 50 mg) of REL-1017 as an adjunctive treatment in patients with MDD unresponsive to standard antidepressants, included 62 patients. We analyzed subjective cognitive measures derived from the MADRS and SDQ scales at baseline and up to day 14, 7 days after the last dose of study drug. We developed 2 composite indexes that included subjective cognitive measures selected from the MADRS and SDQ.

Results: The subanalysis of single measures and the 2 composite indexes derived from the MADRS and SDQ measures showed clinically meaningful and statistically significant improvements in cognitive function (P < .05).

Conclusions: In a Phase 2a clinical trial, REL-1017 improved subjective measures of cognitive impairment, in addition to improving total MADRS and SDQ scores. These results need to be confirmed in larger and longer studies in MDD that include objective measures of cognitive function. Phase 3 studies of REL-1017 for MDD are currently underway.

Clinical Trials Registration: ClinicalTrials.gov identifier: NCT03051256.

PMID:36821775 | DOI:10.4088/PCC.22m03267

Genome Biol Evol. 2023 Feb 23:evad032. doi: 10.1093/gbe/evad032. Online ahead of print.

ABSTRACT

The identification of genomic regions and genes that have evolved under natural selection is a fundamental objective in the field of evolutionary genetics. While various approaches have been established for the detection of targets of positive selection, methods for identifying targets of balancing selection, a form of natural selection that preserves genetic and phenotypic diversity within populations, have yet to be fully developed. Despite this, balancing selection is increasingly acknowledged as a significant driver of diversity within populations, and the identification of its signatures in genomes is essential for understanding its role in evolution. In recent years, a plethora of sophisticated methods have been developed for the detection of patterns of linked variation produced by balancing selection, such as high levels of polymorphism, altered allele frequency distributions, and polymorphism sharing across divergent populations. In this review, we provide a comprehensive overview of classical and contemporary methods, offer guidance on the choice of appropriate methods, and discuss the importance of avoiding artifacts and of considering alternative evolutionary processes. The increasing availability of genome-scale datasets holds the potential to assist in the identification of new targets and the quantification of the prevalence of balancing selection, thus enhancing our understanding of its role in natural populations.

PMID:36821771 | DOI:10.1093/gbe/evad032

Prim Care Companion CNS Disord. 2023 Feb 21;25(1):22r03304. doi: 10.4088/PCC.22r03304.

ABSTRACT

Objective: To better understand Takotsubo cardiomyopathy, a rare but life-threatening complication of acute substance withdrawal.

Data Sources: A PubMed search was conducted to identify relevant case reports through 2021 using the medical subject headings alcohol withdrawal, opioid withdrawal, benzodiazepine withdrawal OR withdrawal AND Takotsubo OR stress cardiomyopathy.

Study Selection: Case reports were included in the review if there was a diagnosis of Takotsubo cardiomyopathy in the setting of withdrawal from substances of abuse. Case reports were excluded if patients were withdrawing from other substances, actively intoxicated, or had myocardial ischemia.

Data Extraction and Synthesis: Data were manually abstracted for the variables of interest, including demographics, symptoms, medical evaluation, and treatment. Descriptive statistics of the demographics, symptoms, medical evaluation, and treatment of Takotsubo cardiomyopathy were analyzed.

Results: The mean (SD) age of patients experiencing withdrawal-associated Takotsubo cardiomyopathy was 50.8 years (15.2), and 64% of patients were female. The most common signs and symptoms were tachycardia (60%), changes in blood pressure (48%), altered mental status (48%), dyspnea (32%), nausea or vomiting (28%), and chest pain (28%). All patients with a reported electrocardiogram (92%) demonstrated ECG abnormalities; 76% had an elevated troponin level, and 24% had an elevated CK-MB level. Medications that could treat withdrawal and α₂-agonists were utilized for 60% and 12% of patients, respectively. Ventilator support, cardiopulmonary resuscitation, and intra-aortic balloon pump were needed for 24%, 8%, and 8%, respectively, of patients with withdrawal-associated Takotsubo cardiomyopathy.

Conclusions: Withdrawal-associated Takotsubo cardiomyopathy is a rare but potentially life-threatening complication of substance withdrawal. Clinicians should maintain a high degree of clinical suspicion for withdrawal-associated Takotsubo in patients with a history of substance use disorders or physical dependence on benzodiazepines or opioids, as the clinical presentation may be atypical.

PMID:36821769 | DOI:10.4088/PCC.22r03304

Occup Med (Lond). 2023 Feb 23:kqad015. doi: 10.1093/occmed/kqad015. Online ahead of print.

ABSTRACT

BACKGROUND: Current evidence is lacking to justify more stringent screening for obstructive sleep apnoea (OSA) in the rail industry. Population-based studies indicate a complex association between body mass index, age, apnoea-hypopnoea index and vehicle crash risk.

AIMS: To study the association between OSA severity and the occurrence of safety incidents in safety-critical rail workers with a confirmed diagnosis of OSA, and to identify if OSA treatment is associated with the occurrence of fewer safety incidents.

METHODS: A retrospective medical file audit was conducted on railway workers attending health assessments between 2016 and 2018, who met the criteria to be referred for sleep studies. The association between OSA severity, treatment and the number of incidents in the 3 years before their health assessment appointment was explored using a Poisson log-linear regression.

RESULTS: A substantial proportion (44%, 274/630) of railway workers with confirmed OSA had at least one incident in the 3 years prior to appointment. The odds of an incident were significantly reduced in those with moderate OSA compared with severe OSA (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.64-0.98), but not those with mild OSA (OR 0.97, 95% CI 0.76-1.24). There was a statistically significant relationship between combined OSA severity and treatment status, where the likelihood of an incident increased in those with severe untreated OSA compared with those receiving treatment (OR 1.75, 95% CI 1.16-2.64).

CONCLUSIONS: Our results suggest that more stringent screening to identify severe OSA early, and close surveillance of treatment of those with severe OSA, should be considered.

PMID:36821744 | DOI:10.1093/occmed/kqad015