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Competing Interests: Conflicts of interest The authors declare no conflicts of interest.

Background: Recent evidence suggests that perioperative semaglutide use is associated with increased residual gastric content (RGC) and risk of bronchoaspiration under anesthesia. We compared the occurrence of increased RGC in semaglutide users and non-users undergoing esophagogastroduodenoscopy to define the time interval at which RGC becomes comparable between groups., Methods: This was a single-center retrospective electronic chart review at a tertiary hospital. Patients undergoing esophagogastroduodenoscopy under deep sedation/general anesthesia between July/2021-July/2023 were included and divided into two (SG = semaglutide, NSG = non-semaglutide) groups, according to whether they had received semaglutide within 30 days prior to the esophagogastroduodenoscopy. Univariate and multivariate logistic regression were performed to explore which factors were associated with increased RGC, defined as any amount of solid content, or > 0.8 mL/Kg (measured from the aspiration/suction canister) of fluid content., Results: Among the 1094 (SG = 123; NSG = 971) patients included, increased RGC was observed in 56 (5.12%), being 25 (20.33%) in the SG and 31 (3.19%) in the NSG (p < 0.001). Following weighted analysis, the presence of ongoing digestive symptoms (nausea/vomiting, dyspepsia, and/or bloating/abdominal distension) pre-esophagogastroduodenoscopy [OR = 15.1 (95% confidence interval (CI) 9.85-23.45)] and the time intervals of preoperative semaglutide interruption < 8 days [OR 10.0 (95%CI 6.67-15.65)] and 8-14 days [4.59 (95%CI 2.91-7.37)] remained significantly associated with increased RGC. Following inverse probability treatment weighting adjustment including a composite variable 'time intervals of semaglutide interruption' versus 'presence of ongoing digestive symptoms', only time intervals > 14 days and without digestive symptoms showed no association with increased RGC [OR = 0.77 (95%CI 0.22-2.01)]., Conclusions: Perioperative semaglutide use is associated with increased RGC in patients undergoing elective esophagogastroduodenoscopy. Preoperative discontinuation of > 21 days and > 14 days in patients with and without ongoing digestive symptoms, respectively, resulted in RGC similar to non-semaglutide users., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Medical errors may be occasionally explained by inattentional blindness (IB), i.e., failing to notice an event/object that is in plain sight. We aimed to determine whether age/experience, restfulness/fatigue, and previous exposure to simulation education may affect IB in the anesthetic/surgical setting., Methods: In this multicentre/multinational study, a convenience sample of 280 anesthesiologists watched an attention-demanding video of a simulated trauma patient undergoing laparotomy and (independently/anonymously) recorded the abnormalities they noticed. The video contained four expected/common abnormalities (hypotension, tachycardia, hypoxia, hypothermia) and two prominently displayed unexpected/rare events (patient's head movement, leaky central venous line). We analyzed the participants' ability to notice the expected/unexpected events (primary outcome) and the proportion of expected/unexpected events according to age group and prior exposure to simulation education (secondary outcomes)., Results: Anesthesiologists across all ages noticed fewer unexpected/rare events than expected/common ones. Overall, younger anesthesiologists missed fewer common events than older participants did (P = 0.02). There was no consistent association between age and perception of unexpected/rare events (P = 0.28), although the youngest cohort (< 30 yr) outperformed the other age groups. Prior simulation education did not affect the proportion of misses for the unexpected/rare events but was associated with fewer misses for the expected/common events. Self-perceived restfulness did not impact perception of events., Conclusion: Anesthesiologists noticed fewer unexpected/rare clinical events than expected/common ones in an attention-demanding video of a simulated trauma patient, in keeping with IB. Prior simulation training was associated with an improved ability to notice anticipated/expected events, but did not reduce IB. Our findings may have implications for understanding medical mishaps, and efforts to improve situational awareness, especially in acute perioperative and critical care settings., (© 2024. Canadian Anesthesiologists' Society.)

Background: Semaglutide is a long-acting glucagon-like peptide-1 receptor agonist known to delay gastric emptying. Despite a growing body of evidence, its peri-operative safety profile remains uncertain, particularly with regard to the risk of increased residual gastric content and aspiration of gastric contents during anaesthesia. We hypothesised that semaglutide interruption of ≤ 10 days before elective surgical procedures is insufficient to reduce or normalise the residual gastric content, despite fasting intervals that comply with current guidelines., Methods: In this prospective observational study, we recruited patients who received pre-operative once-weekly subcutaneous semaglutide within 10 days of the procedure (semaglutide group) and control patients who had not been exposed to semaglutide (non-semaglutide group). On the day of surgery, all patients underwent pre-operative point-of-care gastric ultrasound to evaluate their residual gastric content. Increased residual gastric content was defined as any solid content or > 1.5 ml.kg -1 of clear fluids as assessed by gastric ultrasound., Results: We recruited 220 patients, 107 in the semaglutide group and 113 in the non-semaglutide group. Increased residual gastric content was found in 43/107 patients (40%) in the semaglutide group and 3/113 (3%) in the non-semaglutide group (p < 0.001). In propensity-weighted analysis, semaglutide use (OR 36.97, 95%CI 16.54-99.32), age (OR 0.95, 95%CI 0.93-0.98) and male sex (OR 2.28, 95%CI 1.29-4.06) were significantly associated with increased residual gastric content. There were no cases of pulmonary aspiration of gastric contents., Conclusion: Pre-operative semaglutide use within 10 days of elective surgical procedures was independently associated with increased risk of residual gastric content on pre-operative gastric ultrasound assessment., (© 2024 The Author(s). Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

Acamprosate is a Food and Drug Administration (FDA) approved medication for the treatment of alcohol use disorder (AUD). However, only a subset of patients achieves optimal treatment outcomes. Currently, no biological measures are utilized to predict response to acamprosate treatment. We applied our established pharmaco-omics informed genomics strategy to identify potential biomarkers associated with acamprosate treatment response. Specifically, our previous open-label acamprosate clinical trial recruited 442 patients with AUD who were treated with acamprosate for three months. We first performed proteomics using baseline plasma samples to identify potential biomarkers associated with acamprosate treatment outcomes. Next, we applied our established "proteomics-informed genome-wide association study (GWAS)" research strategy, and identified 12 proteins, including interleukin-17 receptor B (IL17RB), associated with acamprosate treatment response.​ A GWAS for IL17RB concentrations identified several genome-wide significant signals. Specifically, the top hit single nucleotide polymorphism (SNP) rs6801605 with a minor allele frequency of 38% in the European American population mapped 4 kilobase (Kb) upstream of IL17RB, and intron 1 of the choline dehydrogenase (CHDH) gene on chromosome 3 (p: 4.8E-20). The variant genotype (AA) for the SNP rs6801605 was associated with lower IL17RB protein expression. In addition, we identified a series of genetic variants in IL17RB that were associated with acamprosate treatment outcomes. Furthermore, the variantgenotypes for all of those IL17RB SNPs were protective for alcohol relapse. Finally, we demonstrated that the basal level of mRNA expression of IL17RB was inversely correlated with those of nuclear factor-κB (NF-κB) subunits, and a significantly higher expression of NF-κB subunits was observed in AUD patients who relapsed to alcohol use. In summary, this study illustrates that IL17RB genetic variants might contribute to acamprosate treatment outcomes. This series of studies represents an important step toward generating functional hypotheses that could be tested to gain insight into mechanisms underlying acamprosate treatment response phenotypes. (The ClinicalTrials.gov Identifier: NCT00662571)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Insects encounter various environmental stresses, in response to which they generate reactive oxygen species (ROS). Superoxide dismutase (SOD) is an antioxidant metalloenzyme that scavenges superoxide radicals to prevent oxidative damage., Objective: To investigate expressions of SODs under oxidative stress in Tenebrio molitor., Methods: Here, we investigated the transcriptional expression of SODs by pesticide and heavy metals in Tenebrio moltior. First, we searched an RNA-Seq database for T. molitor SOD (TmSOD) genes and identified two SOD isoforms (TmSOD1-iso1 and iso2). We examined their activities under developmental stage, tissue-specific, and various types (pesticide and heavy metal) of oxidative stress by using qPCR., Results: Our results revealed two novel forms of TmSODs. These TmSODs had a copper/zinc superoxide dismutase domain, active site, Cu 2+ binding site, Zn 2+ binding site, E-class dimer interface, and P-class dimer interface. TmSODs (TmSOD1-iso1 and iso2) were expressed in diverse developmental phases and tissues. Pesticides and heavy metals caused an upregulation of these TmSODs., Conclusion: Our findings suggest that the two TmSODs have different functions in T. molitor, providing insights into the detoxification ability of T. molitor., (© 2024. The Author(s) under exclusive licence to The Genetics Society of Korea.)

Purpose: Point-of-care ultrasound (POCUS) allows for rapid bedside assessment and guidance of patient care. Recently, POCUS was included as a mandatory component of Canadian anesthesiology training; however, there is no national consensus regarding the competencies to guide curriculum development. We therefore aimed to define national residency competencies for basic perioperative POCUS proficiency., Methods: We adopted a Delphi process to delineate relevant POCUS competencies whereby we circulated an online survey to academic anesthesiologists identified as POCUS leads/experts (n = 25) at all 17 Canadian anesthesiology residency programs. After reviewing a list of competencies derived from the Royal College of Physicians and Surgeons of Canada's National Curriculum, we asked participants to accept, refine, delete, or add competencies. Three rounds were completed between 2022 and 2023. We discarded items with < 50% agreement, revised those with 50-79% agreement based upon feedback provided, and maintained unrevised those items with ≥ 80% agreement., Results: We initially identified and circulated (Round 1) 74 competencies across 19 clinical domains (e.g., basics of ultrasound [equipment, nomenclature, clinical governance, physics]; cardiac [left ventricle, right ventricle, valve assessment, pericardial effusion, intravascular volume status] and lung ultrasound anatomy, image acquisition, and image interpretation; and clinical applications [monitoring and serial assessments, persistent hypotension, respiratory distress, cardiac arrest]). After three Delphi rounds (and 100% response rate maintained), panellists ultimately agreed upon 75 competencies., Conclusion: Through national expert consensus, this study identified POCUS competencies suitable for curriculum development and assessment in perioperative anesthesiology. Next steps include designing and piloting a POCUS curriculum and assessment tool(s) based upon these nationally defined competencies., (© 2024. Canadian Anesthesiologists' Society.)

Purpose of Review: To summarize the mechanism of action, clinical outcomes, and perioperative implications of glucagon-like peptide-1 receptor agonists (GLP-1-RAs). Specifically, this review focuses on the available literature surrounding complications (primarily, bronchoaspiration) and current recommendations, as well as knowledge gaps and future research directions on the perioperative management of GLP-1-RAs., Recent Findings: GLP-1-RAs are known to delay gastric emptying. Accordingly, recent case reports and retrospective observational studies, while anecdotal, suggest that the perioperative use of GLP-1-RAs may increase the risk of bronchoaspiration despite fasting intervals that comply with (and often exceed) current guidelines. As a result, guidelines and safety bulletins have been published by several Anesthesiology Societies., Summary: While rapidly emerging evidence suggests that perioperative GLP-1-RAs use is associated with delayed gastric emptying and increased risk of bronchoaspiration (particularly in patients undergoing general anesthesia and/or deep sedation), high-quality studies are needed to provide definitive answers with respect to the safety and duration of preoperative drug cessation, and optimal fasting intervals according to the specific GLP-1-RA agent, the dose/duration of administration, and patient-specific factors. Meanwhile, clinicians must be aware of the potential risks associated with the perioperative use of GLP-1-RAs and follow the recommendations put forth by their respective Anesthesiology Societies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Human advancements in agriculture, urbanization, and industrialization have led to various forms of environmental pollution, including heavy metal pollution. Insects, as highly adaptable organisms, can survive under various environmental stresses, which induce oxidative damage and impair antioxidant systems. To investigate the peroxidase (POX) family in Tenebrio molitor, we characterized two POXs, namely TmPOX-iso1 and TmPOX-iso2. The full-length cDNA sequences of TmPox-iso1 and TmPox-iso2 respectively consisted of an open reading frame of 1815 bp encoding 605 amino acids and an open reading frame of 2229 bp encoding 743 amino acids. TmPOX-iso1 and TmPOX-iso2 homologs were found in five distinct insect orders. In the phylogenetic tree analysis, TmPOX-iso1 was clustered with the predicted POX protein of T. castaneum, and TmPOX-iso2 was clustered with the POX precursor protein of T. castaneum. During development, the highest expression level of TmPox-iso1 was observed in the pre-pupal stage, while that of TmPox-iso2 expression were observed in the pre-pupal and 4-day pupal stages. TmPox-iso1 was primarily expressed in the early and late larval gut, while TmPox-iso2 mRNA expression was higher in the fat bodies and Malpighian tubules. In response to cadmium chloride treatment, TmPox-iso1 expression increased at 3 hours and then declined until 24 hours, while in the zinc chloride-treated group, TmPox-iso1 expression peaked 24 hours after the treatment. Both treated groups showed increases in TmPox-iso2 expression 24 hours after the treatments., (© 2024. The Author(s) under exclusive licence to The Genetics Society of Korea.)

Purpose: Rib fracture(s) is a common and painful injury often associated with significant morbidity (e.g., respiratory complications) and high mortality rates, especially in the elderly. Risk stratification and prompt implementation of analgesic pathways using a multimodal analgesia approach comprise a primary endpoint of care to reduce morbidity and mortality associated with rib fractures. This narrative review aims to describe the most recent evidence and care pathways currently available, including risk stratification tools and pharmacologic and regional analgesic blocks frequently used as part of the broadly recommended multimodal analgesic approach., Source: Available literature was searched using PubMed and Embase databases for each topic addressed herein and reviewed by content experts., Principal Findings: Four risk stratification tools were identified, with the Study of the Management of Blunt Chest Wall Trauma score as most predictive. Current evidence on pharmacologic (i.e., acetaminophen, nonsteroidal anti-inflammatory drugs, gabapentinoids, ketamine, lidocaine, and dexmedetomidine) and regional analgesia (i.e., thoracic epidural analgesia, thoracic paravertebral block, erector spinae plane block, and serratus anterior plane block) techniques was reviewed, as was the pathophysiology of rib fracture(s) and its associated complications, including the development of chronic pain and disabilities., Conclusion: Rib fracture(s) continues to be a serious diagnosis, with high rates of mortality, development of chronic pain, and disability. A multidisciplinary approach to management, combined with appropriate analgesia and adherence to care bundles/protocols, has been shown to decrease morbidity and mortality. Most of the risk-stratifying care pathways identified perform poorly in predicting mortality and complications after rib fracture(s)., (© 2024. Canadian Anesthesiologists' Society.)

Apart from their diagnostic, monitoring, or prognostic utility in clinical settings, molecular biomarkers may be instrumental in understanding the pathophysiology of psychiatric disorders, including schizophrenia. Using untargeted metabolomics, we recently identified eight cerebrospinal fluid (CSF) metabolites unique to first-episode psychosis (FEP) subjects compared to healthy controls (HC). In this study, we sought to investigate the CSF proteomic signatures associated with FEP. We employed 16-plex tandem mass tag (TMT) mass spectrometry (MS) to examine the relative protein abundance in CSF samples of 15 individuals diagnosed with FEP and 15 age-and-sex-matched healthy controls (HC). Multiple linear regression model (MLRM) identified 16 differentially abundant CSF proteins between FEP and HC at p < 0.01. Among them, the two most significant CSF proteins were collagen alpha-2 (IV) chain (COL4A2: standard mean difference [SMD] = -1.12, p = 1.64 × 10 -4 ) and neuron-derived neurotrophic factor (NDNF: SMD = -1.03, p = 4.52 × 10 -4 ) both of which were down-regulated in FEP subjects compared to HC. We also identified several potential CSF proteins associated with the pathophysiology and the symptom profile and severity in FEP subjects, including COL4A2, NDNF, hornerin (HRNR), contactin-6 (CNTN6), voltage-dependent calcium channel subunit alpha-2/delta-3 (CACNA2D3), tropomyosin alpha-3 chain (TPM3 and TPM4). Moreover, several protein signatures were associated with cognitive performance. Although the results need replication, our exploratory study suggests that CSF protein signatures can be used to increase the understanding of the pathophysiology of psychosis., Competing Interests: Declaration of competing interest All authors declare that the research was conducted without commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: Conflicts of interest The authors declare no have conflicts of interest.

The primary objective of our study was to determine the proportion of intermediate-risk PE patients undergoing mechanical thrombectomy (MT) who achieved therapeutic anticoagulation (AC) at the time of the procedure. The salient findings of our study showed that only a minority of patients (14.3%) were in the therapeutic range by ACT at the time of MT (primary outcome). Furthermore, in this higher-risk PE cohort selected for MT, 18.2% of patients were subtherapeutic after initially reaching therapeutic AC, 43% experienced supratherapeutic AC at some point before MT, and less than half (43%) attained therapeutic AC at 6 hours, highlighting the necessity for optimizing anticoagulation practices in acute PE., Competing Interests: Conflict of interest Dr. Bangalore- Advisory board- Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, REATA, Inari, Truvic, Argon., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Breast reconstruction is an integral part of breast cancer care. There are 2 main types of breast reconstruction: alloplastic (using implants) and autologous (using the patient's own tissue). The latter creates a more natural breast mound and avoids the long-term need for surgical revision-more often associated with implant-based surgery. The deep inferior epigastric perforator (DIEP) flap is considered the gold standard approach in autologous breast reconstruction. However, complications do occur with DIEP flap surgery and can stem from poor flap tissue perfusion/oxygenation. Hence, the development of strategies to enhance flap perfusion (eg, goal-directed perioperative fluid therapy) is essential. Current perioperative fluid therapy is traditionally guided by subjective criteria, which leads to wide variations in clinical practice., Objective: The main objective of this trial is to determine whether the use of minimally invasive cardiac output (CO) monitoring for guiding intravenous fluid administration, combined with low-dose dobutamine infusion (via a treatment algorithm), will increase tissue oxygenation in patients undergoing DIEP flap surgery., Methods: With appropriate institutional ethics board and Health Canada approval, patients undergoing DIEP flap surgery are randomly assigned to receive CO monitoring for the guidance of intraoperative fluid therapy in addition to a low-dose dobutamine infusion (which potentially improves flap oxygenation) versus the current standard of care. The primary outcome is tissue oxygenation measured via near-infrared spectroscopy at the perfusion zone furthest from the perforator vessels 45 minutes after vascular reanastomosis of the DIEP flap. Low dose (2.5 μg/kg/hr) dobutamine infusion continues for up to 4 hours postoperatively, provided there are no associated complications (ie, persistent tachycardia). Flap oxygenation, hemodynamic parameters, and any medication-associated side effects/complications are monitored for up to 48 hours postoperatively. Complications, rehospitalizations, and patient satisfaction are also collected until 30 days postoperatively., Results: Funding and regulatory approvals were obtained in 2019, but the study recruitment was interrupted by the COVID-19 pandemic. As of October 4, 2023, 34 participants have been recruited. Because of the significant delays associated with the pandemic, the expected completion date was extended. We expect the study to be completed and ready for potential news release (as appropriate) and publication by July 2024. No patients have suffered any adverse effects/complications from participating in this study, and none have been lost to follow-up., Conclusions: CO-directed fluid therapy in combination with a low-dose dobutamine infusion via a treatment algorithm has the potential to improve DIEP flap tissue oxygenation and reduce complications following DIEP flap breast reconstruction surgery. However, given that the investigators remain blinded to group randomization, no comment can be made regarding the efficacy of this intervention for improving tissue oxygenation at this time. Nevertheless, no patients have been withdrawn for safety concerns thus far, and compliance remains high., Trial Registration: Clinicaltrials.gov NCT04020172; https://clinicaltrials.gov/study/NCT04020172., (©Glenio B Mizubuti, Anthony M-H Ho, Rachel Phelan, Deborah DuMerton, Jessica Shelley, Elorm Vowotor, Jessica Xiong, Bethany Smethurst, Michael McMullen, Wilma M Hopman, Glykeria Martou, Robert Wesley Edmunds, Robert Tanzola. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 22.11.2023.)

Mealworms beetles, Tenebrio molitor, are the limelight next-generation food for humans due to their high nutrient contents. Since Tenebrio molitor is used as feed for pets and livestock in addition to their ability to decompose polystyrene and plastic waste, it is recognized as an insect with an industrial core value. Therefore, it is important to study the immune mechanism related to the development and infection of mealworms for mass breeding purposes. The immune deficiency (Imd) signaling is one of the main pathways with pivotal roles in the production of antimicrobial peptides (AMPs). Transforming growth factor-β activated kinase (TAK1) is one of the Imd pathway components, forms a complex with TAK1 binding protein 2 (TAB2) to ultimately help activate the transcription factor Relish and eventually induce host to produce AMPs. Relatively, little has been revealed about TAK1 in insect models, especially in the T. molitor. Therefore, this study was conducted to elucidate the function of TmTak1 in T. molitor. Our results showed that the highest and lowest mRNA expression of TmTak1 were found in egg and young larvae respectively. The tissue-specific expression patterns were reported in the gut of T. molitor larvae and the fat bodies of adults. Systemic microbial challenge illustrated TmTak1 high expression following the fungal infection in all dissected tissues except for the whole body. However, silencing TmTak1 experiments showed that the survivability of T. molitor larvae affected significantly following Escherichia coli infection. Accordingly, AMP induction after TmTak1 knock down was mainly reported in the integument and the fat bodies., (© 2023. The Author(s).)

Toll and IMD pathways regulate antimicrobial innate immune responses in insect model systems. The transcriptional activation of antimicrobial peptides (AMPs) confers humoral immunity in the host against invaded pathogens. The IKK kinase complex (IKKα, IKKβ, and the regulatory subunit IKKγ/NEMO) centrally regulates the NF-κB response to various stimuli. It triggers an appropriate antimicrobial immune response in the host. In this study, a TmIKKβ (or TmIrd5) homolog was screened from the RNA-seq database of the coleopteran beetle, Tenebrio molitor. A single exon characterizes the TmIKKβ gene, and the open reading frame (ORF) comprises of 2112 bp that putatively encodes a polypeptide of 703 amino acid residues. TmIKKβ contains a serine/threonine kinase domain and is phylogenetically close to Tribolium castaneum IKKβ homolog (TcIKKβ). TmIKKβ transcripts were highly expressed in the early pupal (P1) and adult (A5) stages. Among the tissues, TmIKKβ showed higher expression in the integument of the last instar larvae and the fat body and hemocytes of 5-day-old adults. TmIKKβ mRNA was upregulated post-E. coli challenge to the host. Moreover, RNAi-based TmIKKβ mRNA silencing increased host larvae' susceptibility against E. coli, S. aureus and C. albicans. TmIKKβ RNAi in the fat body led to a downregulation in mRNA expression of ten out of fourteen AMP genes, including TmTenecin1, -2, and -4; TmDefensin, and -like; TmColeoptericinA, and -B; and TmAttacin1a, -1b, and -2, suggesting the requirement of the gene in antimicrobial innate immune responses. Further, a decrease in the mRNA expression of NF-κB factors such as TmRelish, TmDorsal1, and TmDorsal2 in the fat body of T. molitor larvae was observed post-microorganisms challenge. Thus, TmIKKβ regulates antimicrobial innate immune responses in T. molitor., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Study Objective: Semaglutide is a long-acting glucagon-like peptide-1 receptor agonist used for management of type 2 diabetes and/or obesity. To test the hypothesis that perioperative semaglutide use is associated with delayed gastric emptying and increased residual gastric content (RGC) despite adequate preoperative fasting, we compared the RGC of patients who had and had not taken semaglutide prior to elective esophagogastroduodenoscopy. The primary outcome was the presence of increased RGC., Design: Single-center retrospective electronic chart review., Setting: Tertiary hospital., Patients: Patients undergoing esophagogastroduodenoscopy under deep sedation/general anesthesia between July/2021-March/2022., Interventions: Patients were divided into two (SG = semaglutide, NSG = non-semaglutide) groups, according to whether they had received semaglutide within 30 days prior to the esophagogastroduodenoscopy., Measurements: Increased RGC was defined as any amount of solid content, or > 0.8 mL/Kg (measured from the aspiration/suction canister) of fluid content., Main Results: Of the 886 esophagogastroduodenoscopies performed, 404 (33 in the SG and 371 in the NSG) were included in the final analysis. Increased RGC was observed in 27 (6.7%) patients, being 8 (24.2%) in the SG and 19 (5.1%) in the NSG (p < 0.001). Semaglutide use [5.15 (95%CI 1.92-12.92)] and the presence of preoperative digestive symptoms (nausea/vomiting, dyspepsia, abdominal distension) [3.56 (95%CI 2.2-5.78)] were associated with increased RGC in the propensity weighted analysis. Conversely, a protective [0.25 (95%CI 0.16-0.39)] effect against increased RGC was observed in patients undergoing esophagogastroduodenoscopy combined with colonoscopy. In the SG, the mean time of preoperative semaglutide interruption in patients with and without increased RGC was 10.5 ± 5.5 and 10.2 ± 5.6 days, respectively (p = 0.54). There was no relationship between semaglutide use and the amount/volume of RGC found on esophagogastroduodenoscopy (p = 0.99). Only one case (in the SG) of pulmonary aspiration was reported., Conclusions: Semaglutide was associated with increased RGC in patients undergoing elective esophagogastroduodenoscopy. Digestive symptoms prior to esophagogastroduodenoscopy were also predictive of increased RGC., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Although Toll-like receptors have been widely identified and functionally characterized in mammalian models and Drosophila , the immunological function of these receptors in other insects remains unclear. Here, we explored the relevant innate immune response of Tenebrio molitor ( T. molitor ) Toll-3 against Gram-negative bacteria, Gram-positive bacteria, and fungal infections. Our findings indicated that TmToll-3 expression was mainly induced by Candida albicans infections in the fat bodies, gut, Malpighian tubules, and hemolymph of young T . molitor larvae. Surprisingly, Escherichia coli systemic infection caused mortality after TmToll-3 knockdown via RNA interference (RNAi) injection, which was not observed in the control group. Further analyses indicated that in the absence of TmToll-3 , the final effector of the Toll signaling pathway, antimicrobial peptide (AMP) genes and relevant transcription factors were significantly downregulated after E. coli challenge. Our results indicated that the expression of almost all AMP genes was suppressed in silenced individuals, whereas the expression of relevant genes was positively regulated after fungal injection. Therefore, this study revealed the immunological involvement of TmToll-3 in T. molitor in response to systematic infections.

Objectives: The American Society of Regional Anesthesia and Pain Medicine's guidelines recommend a 1-hour interval after neuraxial anesthesia (NA) before systemic heparinization to mitigate the risk of spinal hematoma (SH). The study authors aimed to characterize the time interval between NA and systemic heparinization in vascular surgery patients (primary outcome). The secondary outcomes included the historic incidence of SH, and risk estimation of the SH formation based on available data. Heparin dose, length of surgery, difficulty and/or the number of NA attempts, and patient demographics were recorded., Design: A retrospective analysis between April 2012 and April 2022., Setting: A single (academic) center., Participants: Vascular surgery patients., Interventions: Intravenous heparin administration., Measurements and Main Results: All (N = 311) vascular patients were reviewed, of whom 127 (5 femoral-femoral bypass, 67 femoral-popliteal bypass, and 55 endovascular aneurysm repairs [EVAR]) received NA and were included in the final analysis. Patients receiving general anesthesia alone (N = 184) were excluded. Neuraxial anesthesia included spinal (N = 119), epidural (N = 4), or combined spinal-epidural (N = 4) blocks. The average time between NA and heparin administration was 42.8 ± 22.1 minutes, with 83.7% of patients receiving heparin within 1 hour of NA. The time between NA and heparin administration was 40.4 ± 22.3, 50.1 ± 23.4, and 31.3 ± 12.5 minutes for femoral-femoral bypass, femoral-popliteal bypass, and EVAR, respectively. Heparin was administered after 1 hour of NA in 20% of femoral-femoral bypass, 27% of femoral-popliteal bypass, and 3.9% of EVAR patients. No SHs were reported during the study period., Conclusions: The vast majority of vascular surgery patients at the authors' center received heparin within 1 hour of NA. Further studies are required to assess if their findings are consistent in other vascular surgery settings and/or centers., Competing Interests: Conflict of Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Trehalose, a nonreducing disaccharide, functions as a stress protectant in many organisms, including bacteria. In symbioses involving bacteria, the bacteria have to overcome various stressors to associate with their hosts; thus, trehalose biosynthesis may be important for symbiotic bacteria. Here, we investigated the role of trehalose biosynthesis in the Burkholderia -bean bug symbiosis. Expression levels of two trehalose biosynthesis genes, otsA and treS , were elevated in symbiotic Burkholderia insecticola cells, and hence mutant Δ otsA and Δ treS strains were generated to examine the functions of these genes in symbiosis. An in vivo competition assay with the wild-type strain revealed that fewer Δ otsA cells, but not Δ treS cells, colonized the host symbiotic organ, the M4 midgut, than wild-type cells. The Δ otsA strain was susceptible to osmotic pressure generated by high salt or high sucrose concentrations, suggesting that the reduced symbiotic competitiveness of the Δ otsA strain was due to the loss of stress resistance. We further demonstrated that fewer Δ otsA cells infected the M4 midgut initially but that fifth-instar nymphs exhibited similar symbiont population size as the wild-type strain. Together, these results demonstrated that the stress resistance role of otsA is important for B. insecticola to overcome the stresses it encounters during passage through the midgut regions to M4 in the initial infection stage but plays no role in resistance to stresses inside the M4 midgut in the persistent stage. IMPORTANCE Symbiotic bacteria have to overcome stressful conditions present in association with the host. In the Burkholderia -bean bug symbiosis, we speculated that a stress-resistant function of Burkholderia is important and that trehalose, known as a stress protectant, plays a role in the symbiotic association. Using otsA , the trehalose biosynthesis gene, and a mutant strain, we demonstrated that otsA confers Burkholderia with competitiveness when establishing a symbiotic association with bean bugs, especially playing a role in initial infection stage. In vitro assays revealed that otsA provides the resistance against osmotic stresses. Hemipteran insects, including bean bugs, feed on plant phloem sap, which may lead to high osmotic pressures in the midguts of hemipterans. Our results indicated that the stress-resistant role of otsA is important for Burkholderia to overcome the osmotic stresses present during the passage through midgut regions to reach the symbiotic organ.

Aims: Brain-derived neurotrophic factor (BDNF) levels may be associated with alcohol use disorders (AUD) and alcohol consumption, correlate with sleep disturbance and be influenced by sex differences and sex hormones. These associations have not been examined in a single sample accounting for all these factors., Methods: Data from 190 participants (29.4% female) with AUD were utilized. Sleep quality, craving intensity, depression, anxiety and alcohol consumption were assessed using the Pittsburgh Sleep Quality Index (PSQI), Penn Alcohol Craving Scale (PACS), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7) and Timeline Follow Back for 90 days(TLFB 90). Inventory of Drug Taking Situations (IDTS) assessed the tendency to drink in positive/negative emotional states. Serum BDNF (sBDNF) and plasma sex hormones (estrogen, progesterone, testosterone, FSH and SHBG) were measured. Pearson correlation analyses were used to examine the association between sBDNF and these measures in the entire sample and in men and women separately. Higher order interaction effects between these factors were evaluated for their association with sBDNF using a backward selection model., Results: No significant correlations between sBDNF levels and sex hormones, PSQI, PHQ-9, PACS, IDTS scores and alcohol consumption were found (all P-values > 0.05). sBDNF levels were negatively correlated with GAD-7 scores in men (r = -0.1841; P = 0.03). When considering all quadratic and two-way interactions among PSQI, PHQ-9, GAD-7, mean and max drinks/day, number of drinking days, heavy drinking days, and sex no higher order moderating effects of sBDNF levels were found., Conclusion: Our study revealed no significant associations between sBDNF and alcohol measures, sleep, depression and sex hormones suggesting limited utility as a biomarker., (© The Author(s) 2023. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

Background: Sex-related steroid hormones and proteins may contribute to the sex differences in the characteristics and health consequences of alcohol use disorder. This study aimed to examine the associations between alcohol dependence (AD) and sex-related hormones/proteins using a population-based dataset., Methods: We retrieved serum total testosterone (TT) and estradiol (TE2), sex hormone binding globulin (SHBG), and albumin levels along with clinical data from the UK Biobank. Hormone/protein levels were compared between AD (lifetime AD and/or related diagnoses; 2218 males; 682 females) and control (no aforementioned diagnoses and AUDIT<8; 198,058 males; 250,830 females) groups with sex-dependent linear regression models adjusting for age and body mass index. Moderation and mediation analyses were performed to test whether SHBG was a moderator and/or mediator between hormones and AD or current drinking., Results: AD males had higher TT, TE2, and SHBG levels but lower bioavailable testosterone, bioavailable estradiol, and albumin levels than controls (p adjusted <0.001). After adjusting for menopause, AD females had higher TT and lower albumin levels than controls (p adjusted <0.001). These differences remained after accounting for current drinking frequency (p < 0.001). SHBG moderated TT's effect on AD in males (p interaction <0.001). SHBG was a positive mediator between TT and AD in both sexes and between TE2 and AD in males (p < 0.001), but a negative mediator between TT and current drinking in controls (both sexes) and AD males (p < 0.001)., Conclusions: Testosterone and estradiol levels are altered in males and females with AD distinctly regardless of current drinking frequency. SHBG may play a critical role in these associations., Competing Interests: Declaration of Competing Interest No conflict declared., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Symbiosis requires the adaptation of symbiotic bacteria to the host environment. Symbiotic factors for bacterial adaptation have been studied in various experimental models, including the Burkholderia -bean bug symbiosis model. Previously identified symbiotic factors of Burkholderia symbionts of bean bugs provided insight into the host environment being stressful to the symbionts. Because DegP, which functions as both a protease and a chaperone, supports bacterial growth under various stressful conditions, we hypothesized that DegP might be a novel symbiotic factor of Burkholderia symbionts in the symbiotic association with bean bugs. The expression level of degP was highly elevated in symbiotic Burkholderia cells in comparison with cultured cells. When the degP -deficient strain competed for symbiotic association against the wild-type strain, the Δ degP strain showed no symbiotic competitiveness. In vivo monoinfection with the Δ degP strain revealed a lower symbiont titer in the symbiotic organ than that of the wild-type strain, indicating that the Δ degP strain failed to persist in the host. In in vitro assays, the Δ degP strain showed susceptibility to heat and high-salt stressors and a decreased level of biofilm formation. To further determine the role of the proteolytic activity of DegP in symbiosis, we generated missense mutant DegP S248A exhibiting a defect in protease activity only. The Δ degP strain complemented with degP S248A showed in vitro characteristics similar to those of the Δ degP strain and failed to persist in the symbiotic organ. Together, the results of our study demonstrated that the proteolytic activity of DegP, which is involved in the stress resistance and biofilm formation of the Burkholderia symbiont, plays an essential role in symbiotic persistence in the host bean bug. IMPORTANCE Bacterial DegP has dual functions as a protease and a chaperone and supports bacterial growth under stressful conditions. In symbioses involving bacteria, bacterial symbionts encounter various stressors and may need functional DegP for symbiotic association with the host. Using the Burkholderia -bean bug symbiosis model, which is a useful model for identifying bacterial symbiotic factors, we demonstrated that DegP is indeed a symbiotic factor of Burkholderia persistence in its host bean bug. In vitro experiments to understand the symbiotic mechanisms of degP revealed that degP confers resistance to heat and high-salt stresses. In addition, degP supports biofilm formation, which is a previously identified persistence factor of the Burkholderia symbiont. Furthermore, using a missense mutation in a protease catalytic site of degP , we specifically elucidated that the proteolytic activity of degP plays essential roles in stress resistance, biofilm formation, and, thus, symbiotic persistence in the host bean bug.

Lifetime history of major depressive disorder (MDD) has a sex-specific association with pretreatment alcohol consumption in patients with alcohol dependence. Here, we investigated the association of genetic load for MDD estimated using a polygenic risk score (PRS) with pretreatment alcohol consumption assessed with Timeline Follow Back in a sample of 287 men and 156 women meeting DSM-IV-TR criteria for alcohol dependence. Preferred drinking situations were assessed using the Inventory of Drug Taking Situations (IDTS). Linear models were used to test for association of normalized alcohol consumption measures with the MDD-PRS, adjusting for ancestry, age, sex, and number of days sober at baseline. We fit models both with and without adjustment for MDD history and alcohol-use-related PRSs as covariates. Higher MDD-PRS was associated with lower 90-day total alcohol consumption in men (β = -0.16, p = 0.0012) but not in women (β = 0.11, p = 0.18). The association of MDD-PRS with IDTS measures was also sex-specific: higher MDD-PRS was associated with higher propensity to drink in temptation-related situations in women, while the opposite (negative association)was found in men. MDD-PRS was not associated with lifetime MDD history in our sample, and adjustment for lifetime MDD and alcohol-related PRSs did not impact the results. Our results suggest that genetic load for MDD impacts pretreatment alcohol consumption in a sex-specific manner, which is similar to, but independent from, the effect of history of MDD. The clinical implications of these findings and contributing biological and psychological factors should be investigated in future studies., Competing Interests: Conflict of Interest Statement Co-authors disclosed relationships with funding sources, which may be perceived as potential conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Repeated excessive alcohol consumption increases the risk of developing cognitive decline and dementia. Hazardous drinking among older adults further increases such vulnerabilities. To investigate whether alcohol induces cognitive deficits in older adults, we performed a chronic intermittent ethanol exposure paradigm (ethanol or water gavage every other day 10 times) in 8-week-old young adult and 70-week-old aged rats. While spatial memory retrieval ascertained by probe trials in the Morris water maze was not significantly different between ethanol-treated and water-treated rats in both age groups after the fifth and tenth gavages, behavioral flexibility was impaired in ethanol-treated rats compared to water-treated rats in the aged group but not in the young adult group. We then examined ethanol-treatment-associated hippocampal proteomic and phosphoproteomic differences distinct in the aged rats. We identified several ethanol-treatment-related proteins, including the upregulations of the Prkcd protein level, several of its phosphosites, and its kinase activity and downregulation in the Camk2a protein level. Our bioinformatic analysis revealed notable changes in pathways involved in neurotransmission regulation, synaptic plasticity, neuronal apoptosis, and insulin receptor signaling. In conclusion, our behavioral and proteomic results identified several candidate proteins and pathways potentially associated with alcohol-induced cognitive decline in aged adults., Competing Interests: The authors declare the following competing financial interest(s): Dr. Doo-Sup Choi is a scientific advisory board member to Peptron Inc. and Peptron had no role in the preparation, review, or approval of the manuscript nor the decision to submit the manuscript for publication. The remaining authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 The Authors. Published by American Chemical Society.)

To describe an alternative method of measuring the Epidural Waveform Analysis (EWA), a technique through which anesthesiologists can confirm the position of a needle and/or catheter tip in the epidural space. EWA consists of epidural catheter transduction with a pressure system typically used for invasive arterial blood pressure monitoring which generates a characteristic oscillatory waveform (provided the catheter tip is within the epidural space) in synchrony with the pulsatile epidural circulation. The technique requires a double-male connector, a 3-way stopcock and an arterial pressure extension tubing along with the patient's existing arterial line setup while ensuring a meticulously sterile technique to mitigate the risks of neuraxial infection. The technique described herein has been successfully and routinely applied within our institution to measure EWA with the advantage of being potentially less wasteful. EWA allows anesthesiologists to confirm the correct position of an epidural needle/catheter. We describe a method of successfully measuring EWA while reducing wastefulness., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

The antimicrobial roles of Toll-like receptors have been mainly identified in mammalian models and Drosophila . However, its immunological function in other insects has yet to be fully clarified. Here, we determined the innate immune response involvement of TmToll-2 encountering Gram-negative, Gram-positive, and fungal infection. Our data revealed that TmToll-2 expression could be induced by Escherichia coli , Staphylococcus aureus , and Candida albicans infections in the fat bodies, gut, Malpighian tubules, and hemolymph of Tenebrio molitor young larvae. However, TmToll-2 silencing via RNAi technology revealed that sole E. coli systemic infection caused mortality in the double-strand RNA TmToll-2 -injected group compared with that in the control group. Further investigation indicated that in the absence of TmToll-2 , the final effector of Toll signaling pathway, antimicrobial peptide (AMP) genes and relevant transcription factors were significantly downregulated, mainly E. coli post-insult. We showed that the expression of all AMP genes was suppressed in the main immune organ of insects, namely, fat bodies, in silenced individuals, while the relevant expressions were not affected after fungal infection. Thus, our research revealed the immunological roles of TmToll-2 in different organs of T. molitor in response to pathogenic insults.

Background: Bipolar disorder (BD) presents with high obesity and type 2 diabetes (T2D) and pathophysiological and phenomenological abnormalities shared with cardiometabolic disorders. Genomic studies may help define if they share genetic liability. This selective review of BD with obesity and T2D will focus on genomic studies, stress their current limitations and guide future steps in developing the field., Methods: We searched electronic databases (PubMed, Scopus) until December 2021 to identify genome-wide association studies, polygenic risk score analyses, and functional genomics of BD accounting for body mass index (BMI), obesity, or T2D., Results: The first genome-wide association studies (GWAS) of BD accounting for obesity found a promising genome-wide association in an intronic gene variant of TCF7L2 that was further replicated. Polygenic risk scores of obesity and T2D have also been associated with BD, yet, no genetic correlations have been demonstrated. Finally, human-induced stem cell studies of the intronic variant in TCF7L2 show a potential biological impact of the products of this genetic variant in BD risk., Limitations: The narrative nature of this review., Conclusions: Findings from BD GWAS accounting for obesity and their functional testing, have prompted potential biological insights. Yet, BD, obesity, and T2D display high phenotypic, genetic, and population-related heterogeneity, limiting our ability to detect genetic associations. Further studies should refine cardiometabolic phenotypes, test gene-environmental interactions and add population diversity., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Liver resection patients may be at an increased risk of local anesthetic (LA) toxicity because the liver is essential for metabolizing LA and producing proteins (mainly α 1 -acid glycoprotein (AAG)) that bind to it and reduce the free (and pharmacologically active/toxic) levels in circulation. The liver resection itself, manipulation during surgery, and pre-existing liver disease may all interfere with normal hepatic protein synthesis and result in an attenuation of the increased AAG (a positive acute-phase protein) that normally occurs postoperatively. The purpose of this study was to determine whether the AAG response is attenuated postoperatively following liver resection and whether patients approach toxicity thresholds with continuous postoperative epidural infusion of bupivacaine., Methods: Prospective, observational study with blood drawn preoperatively, in the postanesthetic care unit, on postoperative day (POD) 2, and prior to discontinuation of epidural analgesia on POD3/POD4. Plasma was analyzed for total and unbound bupivacaine via liquid chromatography-mass spectrometry and AAG via ELISA. Signs/symptoms of local anesthetic systemic toxicity (LAST), pain, and sedation scores were also recorded., Results: For the 19 patients completed, total plasma bupivacaine was correlated with total administered, but unbound levels were not associated with the total administered. Unlike non-hepatectomy surgery where unbound LA plasma levels remain stable (or decrease) with continuous postoperative epidural administration, we observed an overall increase. Several patients approached toxicity thresholds and 47% reported at least one symptom of LAST, but no epidurals were discontinued because of LAST. In contrast to the AAG response reported following major non-liver surgery where AAG levels increase twofold, we observed a reduction until POD2 and the magnitude was proportional to resection weight., Discussion: Our results are supported by the literature in suggesting that major liver resection patients may be at an increased vulnerability for LAST. Factors such as the extent of liver disease, resection and intraoperative blood loss should be considered when using continuous postoperative epidural infusion of bupivacaine and vigilance should be used in monitoring, for signs/symptoms of LAST, even for those subtle and non-specific. Future research will be required to verify these findings., Trial Registration Number: NCT03145805., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The American Society of Anesthesiologists Physical Status (ASA-PS) is a grading system routinely adopted worldwide by physicians to classify patients' overall health status. Concerns have been raised surrounding the subjectiveness of this system, potentially leading to poor inter-rater agreement/reliability. We hypothesized that physicians are overconfident when assigning ASA-PS scores and that presenting them with the ASA-PS definitions/examples would improve accuracy. We therefore evaluated participants' accuracy and self-reported confidence on the ASA-PS Classification System (1) while assigning ASA-PS according to their baseline knowledge/judgment; and (2) after a single exposure to the ASA-PS definitions/examples., Design: Prospective before-and-after web-based study., Participants: 272 anesthesiologists and 114 non-anesthesiologists., Interventions: Participants voluntarily answered a web-based questionnaire consisting of 10 hypothetical cases. They were asked to assign an ASA-PS score and rate their perceived self-confidence level (20-100%) on the accuracy of their assigned score for each case both (1) before and (2) after reviewing the ASA-PS definitions/examples. The correct ASA-PS for each hypothetical case was determined by consensus among investigators., Measurements: Participants' accuracy, self-reported confidence, and calibration of confidence on the application of ASA-PS Classification System. Agreement between measures was tested using kappa coefficient., Results: Anesthesiologists had better accuracy than non-anesthesiologists both on initial [6(5-7) vs. 4(3-5) out of 10; p < 0.001] as well as subsequent [7(6-8) vs. 6(4-7); p < 0.001] ASA-PS score assignments. Participants' self-reported confidence was greater than their accuracy for assigned ASA-PS scores (p < 0.001). ASA-PS agreement between anesthesiologists and non-anesthesiologists was poor (κ < 0.20). Participants' accuracy for hypothetical cases of ASA-PS I, II, and III involving adult patients was overall greater than for ASA-PS IV, V, and III (the latter involving a neonate) for both anesthesiologists and non-anesthesiologists (p < 0.001)., Conclusions: Physicians tend to disagree and be overconfident when assigning ASA-PS scores. A brief consultation of the ASA-PS definitions/examples improves the accuracy for both anesthesiologists and non-anesthesiologists., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Yellow mealworm ( Tenebrio molitor ) is a highly beneficial beetle that serves as an excellent source of edible protein as well as a practical study model. Therefore, studying its immune system is important. Like in other insects, the innate immune response effected through antimicrobial peptides production provides the most critical defense armory in T. molitor . Immune deficiency (Imd) signaling is one of the major pathways involved in the humoral innate immune response in this beetle. However, the nature of the molecules involved in the signaling cascade of the Imd pathway, from recognition to the production of final effectors, and their mechanism of action are yet to be elucidated in T. molitor model. In this review, we present a general overview of the current literature available on the Imd signaling pathway and its identified interaction partners in T. molitor ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jang, Kojour, Patnaik, Han and Jo.)

Psychotic disorders are currently diagnosed by examining the patient's mental state and medical history. Identifying reliable diagnostic, monitoring, predictive, or prognostic biomarkers would be useful in clinical settings and help to understand the pathophysiology of schizophrenia. Here, we performed an untargeted metabolomics analysis using ultra-high pressure liquid chromatography coupled with time-of-flight mass spectroscopy on cerebrospinal fluid (CSF) and serum samples of 25 patients at their first-episode psychosis (FEP) manifestation (baseline) and after 18 months (follow-up). CSF and serum samples of 21 healthy control (HC) subjects were also analyzed. By comparing FEP and HC groups at baseline, we found eight CSF and 32 serum psychosis-associated metabolites with non-redundant identifications. Most remarkable was the finding of increased CSF serotonin (5-HT) levels. Most metabolites identified at baseline did not differ between groups at 18-month follow-up with significant improvement of positive symptoms and cognitive functions. Comparing FEP patients at baseline and 18-month follow-up, we identified 20 CSF metabolites and 90 serum metabolites that changed at follow-up. We further utilized Ingenuity Pathway Analysis (IPA) and identified candidate signaling pathways involved in psychosis pathogenesis and progression. In an extended cohort, we validated that CSF 5-HT levels were higher in FEP patients than in HC at baseline by reversed-phase high-pressure liquid chromatography. To conclude, these findings provide insights into the pathophysiology of psychosis and identify potential psychosis-associated biomarkers., (© 2022. The Author(s).)

Competing Interests: Conflicts of interest The authors declare no conflicts of interest.

Objective: Despite advances in health care and ample resources, post-partum hemorrhage (PPH) rates are increasing in high income countries. Although guidelines recommend therapeutic uterotonics, timing of administration is open to judgement and most often based on (inherently inaccurate) visual estimates of blood loss. With severe hemorrhage, every minute of delay can have significant consequences. Our objective was to examine the timing of uterotonic administration and its impact upon maternal outcomes. We hypothesized that increased time to uterotonic administration following the identification of PPH would be associated with a greater decline in hemoglobin (Hb) and higher odds of hypotension and transfusion., Methods: We reviewed all cases of PPH that occurred at an academic centre between June 2015 and September 2017. All cases of primary PPH (i.e., those declared within 24 h of delivery with estimated blood loss [EBL] >500 mL for vaginal and >1000 mL for cesarean deliveries) were analyzed. Patient records were excluded if they were missing information regarding time of PPH declaration, uterotonic administration, and/or Hb measures, or if a pre-existing medical condition could have contributed to PPH., Results: Of 4397 births, there were 259 (5.9%) cases of primary PPH, of which 128 were included in this analysis. For these patients, each 5-minute delay in uterotonic treatment was associated with 26% higher odds of hypotension following delivery of any type. For vaginal deliveries (n = 86), each 5-minute delay was associated with 31% and 34% higher odds of hypotension and transfusion, respectively., Conclusion: In this study, delay in administration of therapeutic uterotonics was associated with a higher incidence of hypotension and transfusion in primary PPH patients., (Copyright © 2021 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

COVID-19-related in-hospital mortality has been reported at 30.7-47.3% in Brazil, however studies assessing exclusively private hospitals are lacking. This is important because of significant differences existing between the Brazilian private and public healthcare systems. We aimed to determine the COVID-19-related in-hospital mortality and associated risk factors in a Brazilian private network from March/2020 to March/2021. Data were extracted from institutional database and analyzed using Cox regression model. Length of hospitalization and death-related factors were modeled based on available independent variables. In total, 38,937 COVID-19 patients were hospitalized of whom 3058 (7.8%) died. Admission to the intensive care unit occurred in 62.5% of cases, and 11.5% and 3.8% required mechanical ventilation (MV) and renal replacement therapy (RRT), respectively. In the adjusted model, age ≥ 61 years-old, comorbidities, and the need for MV and/or RRT were significantly associated with increased mortality (p < 0.05). Obesity and hypertension were associated with the need for MV and RRT (p < 0.05)., (© 2022. The Author(s).)

Male and female human subjects show contrasting propensities to misuse drugs of addiction, including alcohol. These differences lead to different psychological and neurological consequences, such as the likelihood of developing dependence. The pattern and extent of brain damage in alcohol-use disorder cases also varies with comorbid disease. To explore mechanisms that might underlie these outcomes, we used autopsy tissue to determine mRNA transcript expression in relation to genotype for two GABA A receptor subunit genes. We used quantitative Real-Time PCR to measure GABRA6 and GABRA2 mRNA concentrations in dorsolateral prefrontal and primary motor cortices of alcohol-use disorder subjects and controls of both sexes with and without liver disease who had been genotyped for these GABA A receptor subunit genes. Cirrhotic alcohol-use disorder cases had significantly higher expression of GABRA6 and GABRA2 transcripts than either controls or non-cirrhotic alcohol-use disorder cases. Differences were observed between sexes, genotypes and brain regions. We show that sex differences in subjects with GABRA6 and GABRA2 variants may contribute to differences in susceptibility to alcohol-use disorder and alcohol-induced cirrhosis., (© 2022 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.)

Effective pain control after major surgery in neonates presents many challenges. Parenteral opioids (and co-analgesics) are often used but inadequate analgesia and oversedation are not uncommon. Although continuous thoracic epidural analgesia is highly effective and opioid-sparing, its associated risks and the need for staff with specialised skills and/or neonatal intensive care unit staff buy-in may preclude this option even in many academic centres. We present the case of a six-day-old infant who underwent upper abdominal surgery and received intermittent morphine doses via a tunnelled caudal epidural catheter, which provided satisfactory analgesia and facilitated early extubation.