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Background. Dexmedetomidine is a selective α-2 agonist commonly used for sedation that has been used in obstetric anesthesia for multimodal labor analgesia, postcesarean delivery analgesia, and perioperative shivering. This study evaluated the role of intravenous dexmedetomidine to provide rescue analgesia and/or sedation during cesarean delivery under neuraxial anesthesia. Methods. We conducted a single-center, retrospective cohort study of all parturients undergoing cesarean delivery under neuraxial anesthesia between December 1, 2018, and November 30, 2019, who required supplemental analgesia during the procedure. Patients were divided into two groups: patients who received intravenous dexmedetomidine (Dexmed group) and patients who received adjunct medications such as fentanyl, midazolam, ketamine, and nitrous oxide (Standard group). Primary outcome was incidence of conversion to general anesthesia. Results. During the study period, 107 patients received adjunct medications. There was no difference in conversion to general anesthesia between the Dexmed group and the Standard group (6% (4/62) vs. 9% (4/45); p = 0.718 ). In the Dexmed group, the mean dexmedetomidine dose received was 37 μg (range 10 to 140 μg). While the use of inotropic/vasopressor medications was common and similar in both groups, there was an increase in the incidence of bradycardia (Dexmed 15% vs. Standard 2%; p = 0.042 ) but not hypotension (Dexmed 24% vs. Standard 24%; p = 1.00 ) in the Dexmed group. Conclusion. In patients who required supplemental analgesia for cesarean delivery, those who received dexmedetomidine versus other medications had a similar rate of conversion to general anesthesia, a statistically significant increase in bradycardia, but no difference in the incidence of hypotension.

Background High-impact pathogenic variants in more than a thousand genes are involved in Mendelian forms of neurodevelopmental disorders (NDD). Methods This study describes the molecular and clinical characterisation of 28 probands with NDD harbouring heterozygous AGO1 coding variants, occurring de novo for all those whose transmission could have been verified (26/28). Results A total of 15 unique variants leading to amino acid changes or deletions were identified: 12 missense variants, two in-frame deletions of one codon, and one canonical splice variant leading to a deletion of two amino acid residues. Recurrently identified variants were present in several unrelated individuals: p.(Phe180del), p.(Leu190Pro), p.(Leu190Arg), p.(Gly199Ser), p.(Val254Ile) and p.(Glu376del). AGO1 encodes the Argonaute 1 protein, which functions in gene-silencing pathways mediated by small non-coding RNAs. Three-dimensional protein structure predictions suggest that these variants might alter the flexibility of the AGO1 linker domains, which likely would impair its function in mRNA processing. Affected individuals present with intellectual disability of varying severity, as well as speech and motor delay, autistic behaviour and additional behavioural manifestations. Conclusion Our study establishes that de novo coding variants in AGO1 are involved in a novel monogenic form of NDD, highly similar to the recently reported AGO2 -related NDD.

Key points Raynaud's phenomenon may occur as a primary problem or secondary to an autoimmune disease such as scleroderma, mixed connective tissue disease, SLE, or Sjogren's. Lingual Raynaud's is rare, but it is important to recognize as it is often attributed to autoimmune disease. There is a wide range of symptoms in lingual Raynaud's from asymptomatic to severe, throbbing pain. Meticulous history taking is essential.

ABSTRACT Background The COVID-19 pandemic displaced newly matched emergency medicine “pre-interns” from in-person educational experiences at the end of medical school. This called for novel remote teaching modalities. Objective This study assesses effectiveness of a multisite Accreditation Council for Graduate Medical Education (ACGME) sub-competency-based curricular implementation on Slack during the first wave of the COVID-19 pandemic in the United States. Methods Emergency medicine residency programs were recruited via national organization listservs. Programs designated instructors to manage communications and teaching for the senior medical students who had matched to their programs (pre-interns) in spring/summer 2020. Pre- and post-surveys of trainees and instructors assessed perceived preparedness for residency, perceived effectiveness of common virtual educational modalities, and concern for the pandemic's effects on medical education utilizing a Likert scale of 1 (very unconcerned) to 5 (very concerned). Data were analyzed using descriptive statistics and the t test. Results Of 276 possible residency programs, 28 enrolled. Of 324 possible pre-interns, 297 (91.7%) completed pre-surveys in April/May and 249 (76.9%) completed post-surveys in June/July. The median weeks since performing a physical examination was 8 (IQR 7–12), since attending in-person didactics was 10 (IQR 8–15) and of rotation displacement was 4 (IQR 2–6). Perceived preparedness increased both overall and for 14 of 21 ACGME Milestone topics taught. Instructors reported higher mean concern (4.32, 95% CI 4.23–4.41) than pre-interns (2.88, 95% CI 2.74–3.02) regarding the pandemic's negative effects on medical education. Conclusions Pre-interns reported improvements in residency preparedness after participating in this ACGME sub-competency-based curriculum on Slack.

AbstractElevated blood levels of C‐reactive protein (CRP) have been linked to colorectal cancer (CRC) survival. We evaluated genetic variants associated with CRP levels and their interactions with sex and lifestyle factors in association with CRC‐specific mortality. Our study included 16 142 CRC cases from the International Survival Analysis in Colorectal Cancer Consortium. We identified 618 common single nucleotide polymorphisms (SNPs) associated with CRP levels from the NHGRI‐EBI GWAS Catalog. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between SNPs and CRC‐specific mortality adjusting for age, sex, genotyping platform/study and principal components. We investigated their interactions with sex and lifestyle factors using likelihood ratio tests. Of 5472 (33.9%) deaths accrued over up to 10 years of follow‐up, 3547 (64.8%) were due to CRC. No variants were associated with CRC‐specific mortality after multiple comparison correction. We observed strong evidence of interaction between variant rs1933736 at FRK gene and sex in relation to CRC‐specific mortality (corrected Pinteraction = .0004); women had higher CRC‐specific mortality associated with the minor allele (HR = 1.11, 95% CI = 1.04‐1.19) whereas an inverse association was observed for men (HR = 0.88, 95% CI = 0.82‐0.94). There was no evidence of interactions between CRP‐associated SNPs and alcohol, obesity or smoking. Our study observed a significant interaction between sex and a CRP‐associated variant in relation to CRC‐specific mortality. Future replication of this association and functional annotation of the variant are needed.