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The Lake Titicaca Basin is one of the regions in the world where both primary village and state formation occurred in prehistory. Although agriculture has been discussed as the central engine fueling these processes, fish and other aquatic resources were significant but little-understood components of the region's ancient economy. In this paper, we use zooarchaeological analysis of faunal remains from 367 flotation samples recovered from five archaeological sites to discuss the interplay between fishing, environmental change, and the emergence of sociopolitical complexity in the Taraco Peninsula of Lake Titicaca. Our results suggest that fishing comprised a significant component of the local inhabitants' diet between 1500 BC and 1100 AD. The intensity of fish procurement, however, varied through time and independently of both climatic and population change. We interpret variation in fish consumption through time as a product of group and individual decisions to optimize resource use in a context of dynamic environmental and sociopolitical variability. © 2014 Elsevier Inc.

Marc Kelliny, Paul E Croarkin, Katherine M Moore, William V Bobo Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA Abstract: This article reviews the pharmacological profile and available efficacy and tolerability/safety data for vortioxetine, one of the most recent antidepressant drugs to be approved in the USA for the treatment of major depressive disorder (MDD) in adults. The efficacy of vortioxetine for treating MDD in adults is supported by eight positive short-term (6- to 12-weeks) randomized, placebo-controlled trials, and one positive randomized, double-blind, 52-week relapse prevention trial. Based on pooled data from short-term randomized trials and from longer-term studies, vortioxetine appears to be well tolerated and to have a low incidence of adverse effects on sexual functioning. Vortioxetine also appears to be effective for treating symptoms of MDD in the elderly based on the results of one randomized trial for which recruitment was focused on this specific population. Nevertheless, effectiveness studies that directly compare the clinical effects of vortioxetine with other established antidepressant drugs are lacking, and there is no evidence as yet that vortioxetine is more clinically effective than other types of antidepressants. Some preliminary suggestions concerning the place of vortioxetine among the broad range of pharmacological treatments for adults with MDD are provided. Keywords: vortioxetine, Lu AA21004, pharmacological profile, pharmacokinetics, drug interactions, adverse effects/side effects/safety, depression, major depression

Richard A Epstein,1 Katherine M Moore,2 William V Bobo2 1Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN, 2Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA Abstract: In pregnant women with major depression, the overarching goal of treatment is to achieve or maintain maternal euthymia, thus limiting both maternal and fetal exposure to the harmful effects of untreated or incompletely treated depression. However, the absence of uniformly effective therapies with guaranteed obstetric and fetal safety makes the treatment of major depression during pregnancy among the most formidable of clinical challenges. Clinicians and patients are still faced with conflicting data and expert opinion regarding the reproductive safety of antidepressants in pregnancy, as well as large gaps in our understanding of the effectiveness of most antidepressants and nonpharmacological alternatives for treating antenatal depression. In this paper, we provide a clinically focused review of the available information on potential maternal and fetal risks of untreated maternal depression during pregnancy, the effectiveness of interventions for maternal depression during pregnancy, and potential obstetric, fetal, and neonatal risks associated with antenatal antidepressant use. Keywords: depression, major depressive disorder, pregnancy, antidepressants, safety

Objective: To determine the risk of congenital cardiac abnormalities associated with use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy.Patients and Methods: We conducted a retrospective review of the medical records of all pregnant women presenting at Mayo Clinic's site in Rochester, MN, from January 1, 1993, to July 15, 2005, and identified 25,214 deliveries. A total of 808 mothers were treated with SSRIs at some point during their pregnancy. We reviewed the medical records of the newborns exposed to SSRIs during pregnancy to analyze their outcomes, specifically for congenital heart disease and persistent pulmonary hypertension of the newborn.Results: Of the study patients, 808 (3.2%) took an SSRI at some point during the antenatal period. Of the 25,214 deliveries, 208 newborns (0.8%) were diagnosed as having congenital heart disease. Of the 808 women exposed to SSRI during pregnancy, 3 (0.4%) had congenital heart disease compared with 205 (0.8%) of the 24,406 women not exposed to an SSRI (P=.23). Of the total number of deliveries, 16 newborns were diagnosed as having persistent pulmonary hypertension of the newborn, none of whom had exposure to SSRIs (P>.99).Conclusion: Our data are reassuring regarding the safety of using SSRIs during pregnancy. [ABSTRACT FROM AUTHOR]

BACKGROUND: The New York City Department of Health and Mental Hygiene (DOHMH) coordinates the administration of timely postexposure prophylaxis (PEP) to contacts of hepatitis A cases, making prompt disease reporting especially valuable. Electronic laboratory reporting (ELR) has been shown to improve timeliness of infectious disease reporting, and DOHMH began receiving hepatitis A reports via ELR in 2002. OBJECTIVES: (1) to quantify the increase in the proportion of hepatitis A reports received electronically, (2) to assess how implementation of ELR affected the reporting time of hepatitis A, and (3) to assess how changes in reporting time impacted the ability to offer timely prophylaxis to contacts. METHODS: We evaluated the proportion of reports received via ELR and the annual reporting time of all hepatitis A reports and quantified the individuals who received PEP from 2000 to 2006. The specific impact of ELR on laboratory reporting time was assessed for nine laboratories certified as of July 2006. RESULTS: The proportion of hepatitis A reports received via ELR increased during the study period to 35 percent in 2006. Electronic laboratory reporting improved the reporting time for most of the laboratories certified to report electronically, with a median decrease of 17 days. In 2006, DOHMH administered PEP to 299 individuals; a fourfold increase from 2000. CONCLUSIONS: Electronic laboratory reporting provides timely disease data to health departments. Increased utilization of ELR can have a remarkable impact on public health surveillance and response. [ABSTRACT FROM AUTHOR]

In September 2004, Kingston, Frontenac, Lennox and Addington (KFL and A) Public Health, in collaboration with the Public Health Division of the Ontario Ministry of Health and Long-Term Care, Queen's University, the Public Health Agency of Canada, Kingston General Hospital and Hotel Dieu Hospital, began a 2-year pilot project to implement and evaluate an emergency department (ED) chief complaint syndromic surveillance system. Our objective was to evaluate a comprehensive and readily deployable real-time regional syndromic surveillance program and to determine its ability to detect gastrointestinal or respiratory outbreaks well in advance of traditional reporting systems. In order to implement the system, modifications were made to the University of Pittsburgh's Real-time Outbreak and Disease Surveillance (RODS) system, which has been successfully integrated into public health systems, and has enhanced communication and collaboration between them and EDs. This paper provides an overview of a RODS-based syndromic surveillance system as adapted for use at a public health unit in Kingston, Ontario. We summarize the technical specifications, privacy and security considerations, data capture, classification and management of the data streams, alerting and public health response. We hope that the modifications described here, including the addition of unique data streams, will provide a benchmark for future Canadian syndromic surveillance systems. [ABSTRACT FROM AUTHOR]

OBJECTIVE: There is a paucity of information regarding the usefulness of non-traditional data streams for real-time syndromic surveillance systems. The objective of this paper is to examine the temporal relation between Ontario's emergency department (ED) visits and telephone health line (Telehealth) call volume for respiratory illnesses to test the feasibility of using Ontario's Telehealth system for real-time surveillance. METHODS: Retrospective time-series data from the National Ambulatory Care Reporting System (NACRS) and the Telehealth Ontario program from June 1, 2004, to March 31, 2006, were analyzed. The added value of Telehealth Ontario data was determined by comparing it temporally with NACRS data, which uses the International Classification of Diseases (ICD) 10-Canadian Enhancement coding system for discharge diagnoses. RESULTS: Telehealth Ontario had 216 105 calls for respiratory complaints, while 819 832 ICD-coded complaints from NACRS were identified with a comparable diagnosis of respiratory illness. Telehealth Ontario call volume was heavily weighted for the 0-4 years age group (49%), while the NACRS visits were mainly from those 18-64 years old (44%). The Spearman rank correlation coefficient was calculated to be 0.97, with the time-series analysis also resulting in significant correlations at lags (semi-monthly) 0 and 1, indicating that increases in Telehealth Ontario call volume correlate with increases in NACRS discharge diagnosis data for respiratory illnesses. CONCLUSION: Telehealth Ontario call volume fluctuation reflects directly on ED respiratory visit data on a provincial basis. These call complaints are a timely, useful and representative data stream that shows promise for integration into a real-time syndromic surveillance system. [ABSTRACT FROM AUTHOR]

Plasma amino acid levels were measured in autistic and Asperger syndrome patients, their siblings, and parents. The results were compared with values from age-matched controls. Patients with autism or Asperger syndrome and their siblings and parents all had raised glutamic acid, phenylalanine, asparagine, tyrosine, alanine, and lysine (p < .05) than controls, with reduced plasma glutamine. Other amino acids were at normal levels. These results show that children with autistic spectrum disorders come from a family background of dysregulated amino acid metabolism and provide further evidence for an underlying biochemical basis for the condition. [ABSTRACT FROM AUTHOR]

This pilot study examined the effect of the Wilbarger brushing and joint compression protocol and sensory diet on symptoms associated with Sensory Defensiveness among 3 women with histories of self-injurious behaviors. Data were collected through interview, the 50-item Sensory Defensiveness Screening for Adults, and patient journals. Treatment lasted approximately 1 month. Symptoms and patterns of role engagement and self-injury were compared before and nine months after treatment. At follow-up all participants were re-engaged in valued roles with no incidents of self-injury. Respective items endorsed by participants on the Sensory Defensiveness Screening for Adults dropped from 58% to 54%, 43% to 18%, and 72% to 36%. This treatment approach appeared to have some positive influence on Sensory Defensive symptoms. Results suggest that it may be useful in treating women with a history of self-injurious behavior and they indicate the need for further investigation of this treatment approach. [ABSTRACT FROM AUTHOR]

The World Health Organization estimates that 58% of pregnant women in developing countries are anemic. In spite of the fact that most ministries of health in developing countries have policies to provide pregnant women with iron in a supplement form, maternal anemia prevalence has not declined significantly where large-scale programs have been evaluated. During the period 1991-98, the MotherCare Project and its partners conducted qualitative research to determine the major barriers and facilitators of iron supplementation programs for pregnant women in eight developing countries. Research results were used to develop pilot program strategies and interventions to reduce maternal anemia. Across-region results were examined and some differences were found but the similarity in the way women view anemia and react to taking iron tablets was more striking than differences encountered by region, country or ethnic group. While women frequently recognize symptoms of anemia, they do not know the clinical term for anemia. Half of women in all countries consider these symptoms to be a priority health concern that requires action and half do not. Those women who visit prenatal health services are often familiar with iron supplements, but commonly do not know why they are prescribed. Contrary to the belief that women stop taking iron tablets mainly due to negative side effects, only about one-third of women reported that they experienced negative side effects in these studies. During iron supplementation trials in five of the countries, only about one-tenth of the women stopped taking the tablets due to side effects. The major barrier to effective supplementation programs is inadequate supply. Additional barriers include inadequate counseling and distribution of iron tablets, difficult access and poor utilization of prenatal health care services, beliefs against consuming medications during pregnancy, and in most countries, fears that taking too much iron may cause too much blood or a big baby, making delivery more difficult. Facilitators include women's recognition of improved physical well being with the alleviation of symptoms of anemia, particularly fatigue, a better appetite, increased appreciation of benefits for the fetus, and subsequent increased demand for prevention and treatment of iron deficiency and anemia. [ABSTRACT FROM AUTHOR]

Background and Aims: Endoscopic mucosal resection (EMR) of large colorectal lesions can be challenging, and residual lesions after EMR can progress to colorectal cancer. We aimed to assess the efficacy and safety of adding thermal ablation of margins [using argon plasma coagulation (APC) or snare tip soft coagulation (STSC)] in reducing recurrence rates after EMR., Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) identified from PubMed, Cochrane Library, and Embase. The primary outcome was the recurrence rate. Secondary outcomes were overall adverse events (AEs) and delayed bleeding. We pre-specified subgroup analyses by lesion size, thermal ablation technique, and resection type. The random-effects model was used to calculate the pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was assessed using the Cochran's Q test and I 2 statistics., Results: We included four RCTs (815 patients and 872 colorectal lesions). Thermal ablation reduced recurrence rates [RR 0.31; 95%CI (0.20-0.47); I 2  = 0%], while the risk of overall AEs [RR 0.93; 95%CI (0.73-1.17); I 2  = 0%] was similar between both groups. The results were consistent in subgroup analyses of APC, STSC, polyps > 20 mm, and piece-meal resection., Conclusion: Thermal ablation of margins following EMR reduced recurrence rates while maintaining a comparable safety profile., Competing Interests: Declarations. Disclosures: Paula Santo, Gilmara Coelho Meine, Erica Uchoa Holanda, Eduardo Cerchi Barbosa, Stefano Baraldo, Angelica Luciana Nau, and Karollyna Maria Henry Moore have no conflicts of interest or financial ties to disclose., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ethylene glycol dinitrate (EGDN) is a nitrate ester explosive widely used in military ordnance and missile systems. This study investigates the decomposition dynamics of the EGDN cation using a comprehensive approach that combines femtosecond time-resolved mass spectrometry (FTRMS) experiments with ab initio electronic structure and molecular dynamics computations. We identify three distinct dissociation time scales for the metastable EGDN cation of approximately 40-60 fs, 340-450 fs, and >2 ps. The observed dissociation time scales are rationalized by electronic and geometric relaxation of multiple EGDN conformers. These insights are crucial for advancing knowledge of the initial molecular decomposition processes that are central to the detonation physics of nitrate esters, which can lead to improving safety protocols and optimizing the performance of nitrate ester explosives in various applications.

Introduction: This paper developed and used practice vignettes to understand sexual assault nurse examiners' perceptions of self-confidence to provide care for Black, Indigenous, and transgender sexual violence survivors. Sexual assault nurse examiners are uniquely positioned to provide patient-centered postsexual violence health care but not all sexual assault nurse examiners receive culturally specific and identity-affirming training. Black/African American, Indigenous, and/or transgender people disproportionately experience sexual violence but may receive poorer health care after sexual violence compared with white cisgender people. Understanding sexual assault nurse examiner confidence to provide this care is paramount to improving sexual assault nurse examiner training and patient outcomes., Methods: In collaboration with a nurse advisory board, researchers developed and validated 3 case vignettes that manipulated the race or gender of the patient. A fourth previously validated vignette that assessed sexual assault nurse examiner care for a transgender patient also was administered. Sexual assault nurse examiners then answered questions about their confidence to provide (1) a patient-centered safety plan, (2) patient-centered referrals, and (3) care without personal biases influencing care. The current study used a cross-sectional online self-report survey with 4 sexual assault nurse examiner patient vignettes randomized across a convenience sample of 70 sexual assault nurse examiners recruited from a midwestern state., Results: On average, sexual assault nurse examiners rated the vignettes as realistic. Sexual assault nurse examiners reported lower confidence to develop a patient-centered safety plan, provide care without allowing personal biases to influence that care, and provide patient-centered referrals for Black, Indigenous, and/or transgender survivors compared with white cisgender survivors., Discussion: Training and mentorship programs could improve sexual assault nurse examiner confidence to provide trauma- and violence-informed care for Black, Indigenous, and transgender survivors, and vignettes could be used to measure changes in confidence owing to training., (Copyright © 2024 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)

Introduction: Despite advances in obstetric care, postpartum hemorrhage (PPH) is a leading cause of maternal mortality worldwide. Prior reviews of studies published through 2016 suggest an association of antidepressant use during late pregnancy and increased risk of PPH. However, a causal link between prenatal antidepressants and PPH remains controversial. Objectives: This systematic literature review aimed to synthesize the empirical evidence on the association of antidepressant exposure in late pregnancy with the risk of PPH, including studies published before and after 2016. Methods: A systematic literature search was conducted using PubMed, OVID Medline, EMBASE, SCOPUS, PsycINFO, and CINAHL from inception to September 9, 2023. Original, peer-reviewed studies (published in English) that reported on the frequency or risk of PPH in women with evidence of antidepressant use during pregnancy and included at least one control group were included. Results: Twenty studies (eight published after 2016) met inclusion criteria, most of which focused on the risks of PPH associated with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). The main findings from the individual studies were mixed, but the majority documented statistically significant associations of PPH with late prenatal exposure, especially for exposures occurring within 30 days of delivery, compared with unexposed deliveries. Fourteen studies addressed underlying antidepressant indications or their correlates. Few studies focused on prenatal antidepressants and the risk of well-defined severe PPH or on antidepressant dose changes and general PPH risk. None examined competing risks of antidepressant discontinuation on mental health outcomes. Conclusions: Late pregnancy exposure to antidepressants may be a minor risk factor for PPH, but it is unclear to what extent reported associations are causal in nature, as opposed to correlational (effects related to nonpharmacological factors including maternal indication). For patients needing antidepressants during pregnancy, current evidence does not favor routinely discontinuing antidepressants specifically to reduce the risk of PPH.

Pulsed laser ablation in organic solvents is widely used to produce oxide-free metal and metal carbide nanoparticles, often with carbon coatings resulting from laser-induced reactions in the organic solvent. To gain insight into how the molecular structure of the solvent affects these reaction pathways, this work investigates ablation of the C 6 H 14 isomers n -hexane, 2-methylpentane, and 3-methylpentane through characterization of the gas and liquid products with mass spectrometry. Ablation of each C 6 H 14 isomer produces a distinct distribution of product molecular weights and isomers. 2-methylpentane preferentially produces C 3 and C 9 , whereas 3-methylpentane produces C 2 , C 4 , C 8 , and C 10 products. These preferential product distributions, along with the lack of such selectivity in n -hexane, arise from differences in the most favorable C-C bond scission pathways in each C 6 H 14 isomer. Moreover, the particular isomers of C 8 H 18 , C 9 H 20 , C 10 H 22 , and C 12 H 26 produced by ablation of each C 6 H 14 isomer indicate that the vast majority of reaction pathways involve addition reactions between a fragment radical and parent C 6 H 14 or between two C 6 H 14 molecules, without molecular rearrangement. This propensity toward direct addition suggests that the chemical reactions induced by ultrashort pulsed laser ablation proceed on faster time scales than those of radical rearrangements.

Introduction: Lithium remains a gold standard treatment for bipolar disorder including during peripartum. Historically, guidelines advised against breastfeeding while taking lithium though recent data suggest it is acceptable for a healthy infant. Lack of awareness of acceptability contributes to decreased patient and clinician comfort and low breastfeeding rates. We report current breastfeeding rates, monitoring practices, and infant outcomes with lithium exposure in breastmilk at our institution. Methods: A retrospective chart review was conducted at a single academic medical center using records from 2013 to 2023. Electronic medical records were queried to identify patients prescribed lithium postpartum. Data were collected on timing of lithium initiation, lithium dose and concentration, breastfeeding status, and infant outcomes. Results: A total of 18 cases of lithium use in the postpartum period were identified. A total of 39% ( n = 7) of patients taking lithium postpartum breastfed. Most patients, 61% ( n = 11), initiated lithium prior to pregnancy, 11% ( n = 2) initiated during pregnancy and 27% ( n = 5) started postpartum. Four infant charts were reviewed with no reports of adverse events. Of these infants, average maternal lithium dose was 750 mg daily, with an average maternal serum lithium concentration of 0.62 mmol/L and average infant serum lithium concentration of 0.16 mmol/L. Conclusion: Our data demonstrate most patients using lithium postpartum have been taking lithium long-term and are not breastfeeding. Lithium exposure in breastmilk appears to be tolerated by healthy infants. There is a need for ongoing research and education on acceptability and infant monitoring recommendations to support patients who would like to breastfeed while on lithium.

Waning immunity and the emergence of immune evasive SARS-CoV-2 variants jeopardize vaccine efficacy leading to breakthrough infections. We have previously shown that innate immune cells play a critical role in controlling SARS-CoV-2. To investigate the innate immune response during breakthrough infections, we modeled breakthrough infections by challenging low-dose vaccinated mice with a vaccine-mismatched SARS-CoV-2 Beta variant. We found that low-dose vaccinated infected mice had a 2-log reduction in lung viral burden, but increased immune cell infiltration in the lung parenchyma, characterized by monocytes, monocyte-derived macrophages, and eosinophils. Single cell RNA-seq revealed viral RNA was highly associated with eosinophils that corresponded to a unique IFN-γ biased signature. Antibody-mediated depletion of eosinophils in vaccinated mice resulted in increased virus replication and dissemination in the lungs, demonstrating that eosinophils in the lungs are protective during SARS-CoV-2 breakthrough infections. These results highlight the critical role for the innate immune response in vaccine mediated protection against SARS-CoV-2.

Background: Intimate Partner Violence (IPV) is a significant public health concern that disproportionately impacts Indigenous American women more than any other ethnic/racial group in the United States., Purpose: This study aims to inform the work of nurses and allied health professionals by providing insight into the lived realities of Indigenous women in urban areas and how IPV manifests in the lives of Indigenous women., Methods: Postcolonial and Indigenous feminist frameworks informed this qualitative study. Using thematic analysis, we analyzed data from semi-structured individual interviews with 34 Indigenous women in large urban areas in the upper Midwest., Findings: This manuscript discusses one broad theme: experiences of IPV during pregnancy and the devastating impacts on women and their children in the form of intergenerational trauma. Under this broad theme, we identified two sub-themes: impacts of IPV on individual pregnancy experiences and linkages to adverse pregnancy-related outcomes related to physical IPV during the childbearing years., Conclusion: This Indigenous-led study informs the development of effective Indigenous-specific interventions to minimize barriers to accessing prenatal care and help-seeking when experiencing IPV to reduce the devastating consequences for Indigenous women and their families., Competing Interests: Declaration of competing interest The authors have disclosed that they have no significant relationships with or financial interest in any commercial companies pertaining to this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The effects of immunodeficiency associated with chronic HIV infection on COVID-19 disease and viral persistence have not been directly addressed in a controlled setting. In this pilot study, we exposed two pigtail macaques (PTMs) chronically infected with SIVmac239, exhibiting from very low to no CD4 T cells across all compartments, to SARS-CoV-2. We monitored the disease progression, viral replication, and evolution, and compared these outcomes with SIV-naïve PTMs infected with SARS-CoV-2. No overt signs of COVID-19 disease were observed in either animal, and the SARS-CoV-2 viral kinetics and evolution in the SIVmac239 PTMs were indistinguishable from those in the SIV-naïve PTMs in all sampled mucosal sites. However, the single-cell RNA sequencing of bronchoalveolar lavage cells revealed an infiltration of functionally inert monocytes after SARS-CoV-2 infection. Critically, neither of the SIV-infected PTMs mounted detectable anti-SARS-CoV-2 T-cell responses nor anti-SARS-CoV-2 binding or neutralizing antibodies. Thus, HIV-induced immunodeficiency alone may not be sufficient to drive the emergence of novel viral variants but may remove the ability of infected individuals to mount adaptive immune responses against SARS-CoV-2.

Background: Forensic nurse examiners, including sexual assault nurse examiners, provide care for survivors holistically through healthcare, emotional support, connection to follow-up care, safety planning, and, if desired, evidence collection to aid in the prosecution of sexual assault. There is increasing recognition that trauma-informed care must also include an understanding of the impacts of structural violence on minoritized patients to ensure health equity., Aim: To help address this guidance gap, we expanded Campbell and colleagues' empowering care model using a trauma- and violence-informed care (TVIC) lens., Methods: We used an iterative discussion-based process that included five joint meetings between a seven-member transdisciplinary research team and a five-member nurse advisory board., Results: In a TVIC-informed empowering care model, we propose behavioral examples for forensic nurses for each of Campbell et al.'s five key domains of empowering care for forensic nurse examinations (i.e., build rapport and establish trust, show compassion, provide patient-directed care, convey professionalism, and provide resource referral and follow-up)., Conclusions: These behavioral examples for nurses can help guide forensic nurse training and practice to reduce disparities in treatment and follow-up support. Structures and systems are needed that enable forensic nurses to provide trauma- and violence-informed empowering care to survivors of sexual assault and, over time, increase the accessibility of forensic nurse examinations and improve patient outcomes., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 International Association of Forensic Nurses.)

Zika virus (ZIKV) is a mosquito-borne flavivirus that caused an epidemic in the Americas in 2016 and is linked to severe neonatal birth defects, including microcephaly and spontaneous abortion. To better understand the host response to ZIKV infection, we adapted the 10× Genomics Chromium single-cell RNA sequencing (scRNA-seq) assay to simultaneously capture viral RNA and host mRNA. Using this assay, we profiled the antiviral landscape in a population of human monocyte-derived dendritic cells infected with ZIKV at the single-cell level. The bystander cells, which lacked detectable viral RNA, expressed an antiviral state that was enriched for genes coinciding predominantly with a type I interferon (IFN) response. Within the infected cells, viral RNA negatively correlated with type I IFN-dependent and -independent genes (the antiviral module). We modeled the ZIKV-specific antiviral state at the protein level, leveraging experimentally derived protein interaction data. We identified a highly interconnected network between the antiviral module and other host proteins. In this work, we propose a new paradigm for evaluating the antiviral response to a specific virus, combining an unbiased list of genes that highly correlate with viral RNA on a per-cell basis with experimental protein interaction data., Importance: Zika virus (ZIKV) remains a public health threat given its potential for re-emergence and the detrimental fetal outcomes associated with infection during pregnancy. Understanding the dynamics between ZIKV and its host is critical to understanding ZIKV pathogenesis. Through ZIKV-inclusive single-cell RNA sequencing (scRNA-seq), we demonstrate on the single-cell level the dynamic interplay between ZIKV and the host: the transcriptional program that restricts viral infection and ZIKV-mediated inhibition of that response. Our ZIKV-inclusive scRNA-seq assay will serve as a useful tool for gaining greater insight into the host response to ZIKV and can be applied more broadly to the flavivirus field., Competing Interests: The authors declare no conflict of interest.

Background: Psychiatric disorders differ in their prevalence, symptom profiles, and disease courses in men and women. However, sex differences in psychiatric disorders have not received enough attention to guide treatment recommendations. This systematic review aims to summarize sex differences in the treatment responses and adverse effects of mood stabilizers and antipsychotics transdiagnostically., Methods: We conducted a systematic review following the PRISMA 2020 statement (CRD42020212478). A literature search was conducted using MEDLINE, Embase, Cochrane Central, PsycINFO, Web of Science Core Collection, and Scopus databases. Studies comparing mood stabilizer or antipsychotic treatment outcomes in men and women were included. JBI critical appraisal checklists were used to assess bias risk., Results: Out of 4866 records, 129 reports (14 on mood stabilizers, 115 on antipsychotics) with varying designs were included. Sample sizes ranged from 17 to 22,774 participants (median = 147). The most common psychiatric diagnoses were schizophrenia spectrum (n = 109, 84.5 %) and bipolar disorders (n = 38, 29.5 %). Only four studies explored sex differences in mood stabilizer treatment response. In 40 articles on antipsychotic treatment response, 18 indicated no sex difference, while 16 showed females had better outcomes. Women had more adverse effects with both mood stabilizers and antipsychotics. The risk of bias was low in 84 (65.1 %) of studies., Limitations: Substantial heterogeneity among the studies precluded performing a meta-analysis., Conclusion: Number of studies focusing on sex differences in treatment outcomes of mood stabilizers is limited. Women may respond better to antipsychotics than men, but also experience more side effects. The impact of pharmacokinetics on sex differences warrants more attention., Competing Interests: Declaration of competing interest ME's spouse is an employee of Sanofi. MAF has received grant support from Assurex Health and Mayo Foundation, received CME travel and honoraria from Carnot Laboratories and American Physician Institute, and has Financial Interest / Stock ownership / Royalties from Chymia LLC. All other authors report no financial relationships with commercial interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

0rtho -Nitroaniline (ONA) is a model for the insensitive high explosive 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) that shares strong hydrogen bonding character between adjacent nitro and amino groups. This work reports femtosecond time-resolved mass spectrometry (FTRMS) measurements and theoretical calculations that explain the high stability of the ONA cation compared with related nitroaromatic molecules. Ab initio calculations found that the lowest-lying electronic excited state of the ONA cation, D 1 , lies more than 2 eV above the ground state, and the energetic barriers to rearrangement and dissociation reactions exceed this D 1 energy. These theoretical results were confirmed by FTRMS pump-probe measurements showing that (1) fragment ions represented less than 30% of the total ion yield when a 10 14 W cm -2 , 1300 nm, 20 fs pump pulse was used to ionize ONA; and (2) 3.1 eV (400 nm) photons were required to induce dissociation of the ONA cation. Stronger coupling between the ground D 0 and excited D 4 states of the ONA cation at the geometry of neutral ONA resulted in a transient enhancement of fragment ion yields at <300 fs pump-probe delay times, prior to relaxation of the ONA cation to its optimal geometry.

There is increasing interest in individualizing treatment selection for more than 25 regulatory approved treatments for major depressive disorder (MDD). Despite an inconclusive efficacy evidence base, antidepressants (ADs) are prescribed for the depressive phase of bipolar disorder (BD) with oftentimes, an inadequate treatment response and or clinical concern for mood destabilization. This study explored the relationship between antidepressant response in MDD and antidepressant-associated treatment emergent mania (TEM) in BD. We conducted a genome-wide association study (GWAS) and polygenic score analysis of TEM and tested its association in a subset of BD-type I patients treated with SSRIs or SNRIs. Our results did not identify any genome-wide significant variants although, we found that a higher polygenic score (PGS) for antidepressant response in MDD was associated with higher odds of TEM in BD. Future studies with larger transdiagnostic depressed cohorts treated with antidepressants are encouraged to identify a neurobiological mechanism associated with a spectrum of depression improvement from response to emergent mania., (© 2024. The Author(s).)

We report a chemically motivated, single-step method to enhance metal deposition onto silicon laser-induced periodic surface structures (LIPSSs) using reactive laser ablation in liquid (RLAL). Galvanic replacement (GR) reactions were used in conjunction with RLAL (GR-RLAL) to promote the deposition of Au and Cu nanostructures onto a Si LIPSS. To increase the deposition of Au, sacrificial metals Cu, Fe, and Zn were used; Fe and Zn also enhanced the deposition of Cu. We show that the deposited metal content, surface morphology, and metal crystallite size can be tuned based on the difference in electrochemical potentials of the deposited and sacrificial metal. Compared to the Au and Cu reference samples, GR more than doubled the metal content on the LIPSS and reduced metal crystallite sizes by up to 20%. The ability to tune the metal content and crystalline domain size simultaneously makes GR-RLAL a potentially useful approach in the manufacturing of functional metal-LIPSS materials such as surface-enhanced Raman spectroscopy substrates.

Imipramine class tricyclic antidepressants have low ionization efficiencies that make them difficult to detect by using secondary ion mass spectrometry. Ultraviolet picosecond laser desorption postionization (ps-LDPI-MS) is examined here for the detection of four tricyclic antidepressants: imipramine, desipramine, amitriptyline, and clomipramine. About 30 ps laser pulses at either 213 nm (5.8 eV) or 355 nm (3.5 eV) are used for desorption of samples under vacuum, 7.9 eV (157 nm) fluorine laser pulses are used for post-ionization, and the ions so formed are detected by time-of-flight mass spectrometry. Detection of imipramine by 213 nm ps-LDPI-MS shows less fragmentation than either 355 nm ps-LDPI-MS or prior results from 800 nm fs-LDPI-MS. Ionization energies of imipramine, desipramine, amitriptyline, and clomipramine are predicted using density functional theory calculations and used to explain the corresponding ps-LDPI-MS data for these four compounds as resulting from single-photon ionization. The experimental observation of low-mass amine-containing fragments with calculated ionization energies below 7.9 eV is attributed mostly to dissociation during laser desorption, followed by single-photon ionization of the neutral fragments rather than the more traditional mechanism of unimolecular dissociation following single-photon ionization of the parent molecule.

Persistent and uncontrolled SARS-CoV-2 replication in immunocompromised individuals has been observed and may be a contributing source of novel viral variants that continue to drive the pandemic. Importantly, the effects of immunodeficiency associated with chronic HIV infection on COVID-19 disease and viral persistence have not been directly addressed in a controlled setting. Here we conducted a pilot study wherein two pigtail macaques (PTM) chronically infected with SIVmac239 were exposed to SARS-CoV-2 and monitored for six weeks for clinical disease, viral replication, and viral evolution, and compared to our previously published cohort of SIV-naïve PTM infected with SARS-CoV-2. At the time of SARS-CoV-2 infection, one PTM had minimal to no detectable CD4+ T cells in gut, blood, or bronchoalveolar lavage (BAL), while the other PTM harbored a small population of CD4+ T cells in all compartments. Clinical signs were not observed in either PTM; however, the more immunocompromised PTM exhibited a progressive increase in pulmonary infiltrating monocytes throughout SARS-CoV-2 infection. Single-cell RNA sequencing (scRNAseq) of the infiltrating monocytes revealed a less activated/inert phenotype. Neither SIV-infected PTM mounted detectable anti-SARS-CoV-2 T cell responses in blood or BAL, nor anti-SARS-CoV-2 neutralizing antibodies. Interestingly, despite the diminished cellular and humoral immune responses, SARS-CoV-2 viral kinetics and evolution were indistinguishable from SIV-naïve PTM in all sampled mucosal sites (nasal, oral, and rectal), with clearance of virus by 3-4 weeks post infection. SIV-induced immunodeficiency significantly impacted immune responses to SARS-CoV-2 but did not alter disease progression, viral kinetics or evolution in the PTM model. SIV-induced immunodeficiency alone may not be sufficient to drive the emergence of novel viral variants.

Mice were immunized with a combination of self-amplifying (sa) RNA constructs for the F1 and V antigens of Yersinia pestis at a dose level of 1 μg or 5 μg or with the respective protein sub-units as a reference vaccine. The immunization of outbred OF1 mice on day 0 and day 28 with the lowest dose used (1 μg) of each of the saRNA constructs in lipid nanoparticles protected 5/7 mice against subsequent sub-cutaneous challenge on day 56 with 180 cfu (2.8 MLD) of a 2021 clinical isolate of Y. pestis termed 10-21/S whilst 5/7 mice were protected against 1800cfu (28MLD) of the same bacteria on day 56. By comparison, only 1/8 or 1/7 negative control mice immunized with 10 μg of irrelevant haemagglutin RNA in lipid nanoparticles (LNP) survived the challenge with 2.8 MLD or 28 MLD Y. pestis 10-21/S, respectively. BALB/c mice were also immunized with the same saRNA constructs and responded with the secretion of specific IgG to F1 and V, neutralizing antibodies for the V antigen and developed a recall response to both F1 and V. These data represent the first report of an RNA vaccine approach using self-amplifying technology and encoding both of the essential virulence antigens, providing efficacy against Y. pestis . This saRNA vaccine for plague has the potential for further development, particularly since its amplifying nature can induce immunity with less boosting. It is also amenable to rapid manufacture with simpler downstream processing than protein sub-units, enabling rapid deployment and surge manufacture during disease outbreaks., 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 © 2023 Shattock, Andrianaivoarimanana, McKay, Randriantseheno, Murugaiah, Samnuan, Rogers, Tregoning, Rajerison, Moore, Laws and Williamson.)

Omicron SARS-CoV-2 variants escape vaccine-induced neutralizing antibodies and cause nearly all current COVID-19 cases. Here, we compared the efficacy of three booster vaccines against Omicron BA.5 challenge in rhesus macaques: mRNA-1273, the Novavax ancestral spike protein vaccine (NVX-CoV2373), or Omicron BA.1 spike protein version (NVX-CoV2515). All three booster vaccines induced a strong BA.1 cross-reactive binding antibody and changed immunoglobulin G (Ig) dominance from IgG1 to IgG4 in the serum. All three booster vaccines also induced strong and comparable neutralizing antibody responses against multiple variants of concern, including BA.5 and BQ.1.1, along with long-lived plasma cells in the bone marrow. The ratio of BA.1 to WA-1 spike-specific antibody-secreting cells in the blood was higher in NVX-CoV2515 animals compared with NVX-CoV2373 animals, suggesting a better recall of BA.1-specific memory B cells by the BA.1 spike-specific vaccine compared with the ancestral spike-specific vaccine. Further, all three booster vaccines induced low levels of spike-specific CD4 but not CD8 T cell responses in the blood. After challenge with SARS-CoV-2 BA.5 variant, all three vaccines showed strong protection in the lungs and controlled virus replication in the nasopharynx. In addition, both Novavax vaccines blunted viral replication in nasopharynx at day 2. The protection against SARS-CoV-2 BA.5 infection in the upper respiratory airways correlated with binding, neutralizing, and ADNP activities of the serum antibody. These data have important implications for COVID-19 vaccine development, because vaccines that lower nasopharyngeal virus may help to reduce transmission.