Effects of (2<i>R</i>,6<i>R</i>)-hydroxynorketamine in assays of acute pain-stimulated and pain-depressed behaviors in mice

by Todd M. Hillhouse, Kaitlyn J. Partridge, Patrick I. Garrett, Sarah C. Honeycutt, Joseph H. Porter

Ketamine has been shown to produce analgesia in various acute and chronic pain states; however, abuse liability concerns have limited its utility. The ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) has been shown to produce antidepressant-like effects similar to ketamine without abuse liability concerns. (2R,6R)-HNK produces sustained analgesia in models of chronic pain, but has yet to be evaluated in models of acute pain. The present study evaluated the efficacy of acute (2R,6R)-HNK administration (one injection) in assays of pain-stimulated (52- and 56-degree hot plate test and acetic acid writhing) and pain-depressed behavior (locomotor activity and rearing) in male and female C57BL/6 mice. In assays of pain-stimulated behaviors, (2R,6R)-HNK (1–32 mg/kg) failed to produce antinociception in the 52- and 56-degree hot plate and acetic acid writhing assays. In assays of pain-depressed behaviors, 0.56% acetic acid produced a robust depression of locomotor activity and rearing that was not blocked by pretreatment of (2R,6R)-HNK (3.2–32 mg/kg). The positive controls morphine (hot plate test) and ketoprofen (acetic acid writhing, locomotor activity, and rearing) blocked pain-stimulated and pain-depressed behaviors. Finally, the effects of intermittent (2R,6R)-HNK administration were evaluated in 52-degree hot plate and pain-depressed locomotor activity and rearing. Intermittent administration of (2R,6R)-HNK also did not produce antinociceptive effects in the hot plate or pain-depressed locomotor activity assays. These results suggest that (2R,6R)-HNK is unlikely to have efficacy in treating acute pain; however, the efficacy of (2R,6R)-HNK in chronic pain states should continue to be evaluated.

Specific nanoprobe design for MRI: Targeting laminin in the blood-brain barrier to follow alteration due to neuroinflammation

by Juan F. Zapata-Acevedo, Mónica Losada-Barragán, Johann F. Osma, Juan C. Cruz, Andreas Reiber, Klaus G. Petry, Amael Caillard, Audrey Sauldubois, Daniel Llamosa Pérez, Aníbal José Morillo Zárate, Sonia Bermúdez Muñoz, Agustín Daza Moreno, Rafaela V. Silva, Carmen Infante-Duarte, William Chamorro-Coral, Rodrigo E. González-Reyes, Karina Vargas-Sánchez

Chronic neuroinflammation is characterized by increased blood-brain barrier (BBB) permeability, leading to molecular changes in the central nervous system that can be explored with biomarkers of active neuroinflammatory processes. Magnetic resonance imaging (MRI) has contributed to detecting lesions and permeability of the BBB. Ultra-small superparamagnetic particles of iron oxide (USPIO) are used as contrast agents to improve MRI observations. Therefore, we validate the interaction of peptide-88 with laminin, vectorized on USPIO, to explore BBB molecular alterations occurring during neuroinflammation as a potential tool for use in MRI. The specific labeling of NPS-P88 was verified in endothelial cells (hCMEC/D3) and astrocytes (T98G) under inflammation induced by interleukin 1β (IL-1β) for 3 and 24 hours. IL-1β for 3 hours in hCMEC/D3 cells increased their co-localization with NPS-P88, compared with controls. At 24 hours, no significant differences were observed between groups. In T98G cells, NPS-P88 showed similar nonspecific labeling among treatments. These results indicate that NPS-P88 has a higher affinity towards brain endothelial cells than astrocytes under inflammation. This affinity decreases over time with reduced laminin expression. In vivo results suggest that following a 30-minute post-injection, there is an increased presence of NPS-P88 in the blood and brain, diminishing over time. Lastly, EAE animals displayed a significant accumulation of NPS-P88 in MRI, primarily in the cortex, attributed to inflammation and disruption of the BBB. Altogether, these results revealed NPS-P88 as a biomarker to evaluate changes in the BBB due to neuroinflammation by MRI in biological models targeting laminin.

Estimating infection prevalence using the positive predictive value of self-administered rapid antigen diagnostic tests: An exploration of SARS-CoV-2 surveillance data in the Netherlands from May 2021 to April 2022

by Koen M.F. Gorgels, Senna C.J.L. van Iersel, Sylvia F.A. Keijser, Christian J.P.A. Hoebe, Jacco Wallinga, Albert J. van Hoek

Measuring the severity of the disease of SARS-CoV-2 is complicated by the lack of valid estimations for the prevalence of infection. Self-administered rapid antigen diagnostic tests (Ag-RDTs) were available in the Netherlands since March 2021, requiring confirmation by reverse-transcription polymerase chain reaction (RT-PCR) for positive results. We explored the possibility of utilizing the positive predictive value (PPV) of Ag-RDTs to estimate SARS-CoV-2 prevalence. We used data from all Public Health service testing facilities between 3 May 2021 and 10 April 2022. The PPV was calculated by dividing the number of positive RT-PCR results by the total number of confirmation tests performed, and used to estimate the prevalence and compared with the number of COVID-19 hospital admissions. In total 3,599,894 cases were included. The overall PPV was 91.8% and 88.8% were symptomatic. During our study period, the estimated prevalence ranged between 2–22% in symptomatic individuals and 2–14% in asymptomatic individuals, with a correlation between the estimated prevalence and hospital admissions two weeks later (r = 0.68 (p

<i>Metarhizium</i> spp. isolates effective against Queensland fruit fly juvenile life stages in soil

by Madita Prince, Aimee C. McKinnon, Diana Leemon, Tim Sawbridge, John Paul Cunningham

Queensland fruit fly, Bactrocera tryoni, Froggatt (Diptera: Tephritidae) is Australia’s primary fruit fly pest species. Integrated Pest Management (IPM) has been adopted to sustainably manage this polyphagous species with a reduced reliance on chemical pesticides. At present, control measures are aimed at the adult stages of the fly, with no IPM tools available to target larvae once they exit the fruit and pupate in the soil. The use of entomopathogenic fungi may provide a biologically-based control method for these soil-dwelling life stages. The effectiveness of fungal isolates of Metarhizium and Beauveria species were screened under laboratory conditions against Queensland fruit fly. In bioassays, 16 isolates were screened for pathogenicity following exposure of third-instar larvae to inoculum-treated vermiculite used as a pupation substrate. The best performing Metarhizium sp. isolate achieved an average percentage mortality of 93%, whereas the best performing Beauveria isolate was less efficient, with an average mortality of 36%. Susceptibility to infection during different development stages was investigated using selected fungal isolates, with the aim of assessing all soil-dwelling life stages from third-instar larvae to final pupal stages and emerging adults. Overall, the third larval instar was the most susceptible stage, with average mortalities between 51–98% depending on the isolate tested. Moreover, adult mortality was significantly higher when exposed to inoculum during pupal eclosion, with mortalities between 56–76% observed within the first nine days post-emergence. The effect of temperature and inoculum concentration on insect mortality were assessed independently with candidate isolates to determine the optimum temperature range for fungal biological control activity and the rate required for application in field conditions. Metarhizium spp. are highly efficacious at killing Queensland fruit fly and have potential for use as biopesticides to target soil-dwelling and other life stages of B. tryoni.

Psychometric properties of the Fluoride Hesitancy Identification Tool (FHIT)

by Adam C. Carle, Isabella Pallotto, Todd C. Edwards, Richard Carpiano, Darragh C. Kerr, Donald L. Chi

Introduction

Some caregivers are hesitant about topical fluoride for their children despite evidence that fluoride prevents caries and is safe. Recent work described a five domain model of caregivers’ topical fluoride hesitancy. We developed the Fluoride Hesitancy Identification Tool (FHIT) item pool based on the model. This study sought to evaluate the FHIT’s psychometric properties in an effort to generate a short, simple to score, reliable, and valid tool that measures caregivers’ topical fluoride hesitancy.

Methods

In 2021 and 2022, we conducted an observational, cross-sectional study of caregivers, collecting data from two independent caregiver samples (n₁ = 523; n₂ = 612). The FHIT item pool included 33 items. We used confirmatory factor analyses (CFA) to examine whether the FHIT items measured five separate domains as hypothesized and to reduce the number of items. We then fit item response theory (IRT) models and computed Cronbach’s alpha for each domain. Last, we examined the construct validity of the FHIT and evaluated scoring approaches.

Results

After dropping 8 items, CFA supported a five factor model of topical fluoride hesitancy, with no cross-loadings (RMSEA = 0.079; SRMR = 0.057; CFI = 0.98; TLI = 0.98). We further reduced the items to four per domain (20 items total). Marginal alphas showed that the item sets provided reliability of ≥0.90 at hesitancy levels at and above average. The domains correlated more strongly with each other and topical fluoride refusal than with other questions on the survey.

Discussion

Our results support the FHIT’s ability to reliably and validly measure five domains of topical fluoride hesitancy using the average score of the four items in each domain.

Genetic profiling of rat gliomas and cardiac schwannomas from life-time radiofrequency radiation exposure study using a targeted next-generation sequencing gene panel

by Ashley M. Brooks, Andrea Vornoli, Ramesh C. Kovi, Thai Vu T. Ton, Miaofei Xu, Ahmed Mashal, Eva Tibaldi, Federica Gnudi, Jian-Liang Li, Robert C. Sills, John R. Bucher, Daniele Mandrioli, Fiorella Belpoggi, Arun R. Pandiri

The cancer hazard associated with lifetime exposure to radiofrequency radiation (RFR) was examined in Sprague Dawley (SD) rats at the Ramazzini Institute (RI), Italy. There were increased incidences of gliomas and cardiac schwannomas. The translational relevance of these rare rat tumors for human disease is poorly understood. We examined the genetic alterations in RFR-derived rat tumors through molecular characterization of important cancer genes relevant for human gliomagenesis. A targeted next-generation sequencing (NGS) panel was designed for rats based on the top 23 orthologous human glioma-related genes. Single-nucleotide variants (SNVs) and small insertion and deletions (indels) were characterized in the rat gliomas and cardiac schwannomas. Translational relevance of these genetic alterations in rat tumors to human disease was determined through comparison with the Catalogue of Somatic Mutations in Cancer (COSMIC) database. These data suggest that rat gliomas resulting from life-time exposure to RFR histologically resemble low grade human gliomas but surprisingly no mutations were detected in rat gliomas that had homology to the human IDH1 p.R132 or IDH2 p.R172 suggesting that rat gliomas are primarily wild-type for IDH hotspot mutations implicated in human gliomas. The rat gliomas appear to share some genetic alterations with IDH1 wildtype human gliomas and rat cardiac schwannomas also harbor mutations in some of the queried cancer genes. These data demonstrate that targeted NGS panels based on tumor specific orthologous human cancer driver genes are an important tool to examine the translational relevance of rodent tumors resulting from chronic/life-time rodent bioassays.

Nasopharyngeal carriage of <i>Streptococcus pneumoniae</i> among children <5 years of age in Indonesia prior to pneumococcal conjugate vaccine introduction

by Dodi Safari, Wa Ode Dwi Daningrat, Jennifer L. Milucky, Miftahuddin Majid Khoeri, Wisiva Tofriska Paramaiswari, Wisnu Tafroji, Korrie Salsabila, Yayah Winarti, Amin Soebandrio, Sri Rezeki Hadinegoro, Ari Prayitno, Lana Childs, Fabiana C. Pimenta, Maria da Gloria Carvalho, Tamara Pilishvili

Pneumococcal conjugate vaccines (PCVs) prevent nasopharyngeal colonization with vaccine serotypes of Streptococcus pneumoniae, leading to reduced transmission of pneumococci and stronger population-level impact of PCVs. In 2017 we conducted a cross-sectional pneumococcal carriage study in Indonesia among children aged

Sex differences in growth and mortality in pregnancy-associated hypertension

by Jess C. Hercus, Katherine X. Metcalfe, Julian K. Christians

Background

It is hypothesized that male fetuses prioritize growth, resulting in increased mortality, whereas females reduce growth in the presence of adversity. Preeclampsia reflects a chronic condition, in which fetuses have the opportunity to adjust growth. If females reduce their growth in response to preeclampsia, but males attempt to maintain growth at the cost of survival, we predict that differences in birthweight between preeclamptic and non-preeclamptic pregnancies will be greater among females, whereas differences in mortality will be greater among males.

Methods

We analysed data from the Centers for Disease Control and Prevention. We compared pregnancies with pregnancy-associated hypertension (PAH) and controls.

Results

The difference in birthweight between pregnancies affected by PAH and controls varied by fetal sex and gestational age. Among pregnancies of White individuals, at 34–35 weeks, the difference between PAH and controls was higher among females, as predicted. However, this pattern was reversed earlier in pregnancy and around term. Such variation was not significant in Black pregnancies. In both Black and White pregnancies, early in gestation, males had lower odds of death in PAH pregnancies, but higher odds of death in control pregnancies, counter to our prediction. Later, males had higher odds of death in PAH and controls, although the increased odds of death in males was not higher in PAH pregnancies than in controls. Overall, the difference in birthweight between surviving and non-surviving infants was greater in males than in females, opposite to our prediction.

Conclusions

The impact of PAH on birthweight and survival varies widely throughout gestation. Differences in birthweight and survival between male and female PAH and controls are generally not consistent with the hypothesis that males prioritize fetal growth more than females, and that this is a cause of increased mortality in males.

Reallocating time between device-measured 24-hour activities and cardiovascular risk in Asian American immigrant women: An isotemporal substitution model

by Chorong Park, Britta Larsen, Simona C. Kwon, Yuhe Xia, Marianna LaNoue, Victoria V. Dickson, Harmony R. Reynolds, Tanya M. Spruill

The 24-hour day consists of physical activity (PA), sedentary behavior, and sleep, and changing the time spent on one activity affects the others. Little is known about the impact of such changes on cardiovascular risk, particularly in Asian American immigrant (AAI) women, who not only have a higher cardiovascular risk but also place greater cultural value on family and domestic responsibilities compared to other racial/ethnic groups. The purpose of this study was to evaluate the effects of reallocating 30 minutes of each 24-hour activity component for another on BMI, waist circumference, and blood pressure in AAI women. Seventy-five AAI women completed 7 days of hip and wrist actigraphy monitoring and were included in the analysis (age = 61.5±8.0 years, BMI = 25.5±3.6 kg/m², waist circumference = 85.9±10.2 cm). Sleep was identified from wrist actigraphy data, and moderate-to-vigorous PA (MVPA), light PA, and sedentary behavior identified from hip actigraphy data. On average, the women spent 0.5 hours in MVPA, 6.2 hours in light PA, 10 hours in sedentary activities, and 5.3 hours sleeping within a 24-hour day. According to the isotemporal substitution models, replacing 30 minutes of sedentary behavior with MVPA reduced BMI by 1.4 kg/m² and waist circumference by 4.0 cm. Replacing that same sedentary time with sleep reduced BMI by 0.5 kg/m² and waist circumference by 1.4 cm. Replacing 30 minutes of light PA with MVPA decreased BMI by 1.6 kg/m² and waist circumference by 4.3 cm. Replacing 30 minutes of light PA with sleep also reduced BMI by 0.8 kg/m² and waist circumference by 1.7 cm. However, none of the behavioral substitutions affected blood pressure. Considering AAI women’s short sleep duration, replacing their sedentary time with sleep might be a feasible strategy to reduce their BMI and waist circumference.

Individual and environmental variables related to outdoor walking among older adults: Verifying a model to guide the design of interventions targeting outdoor walking

by Yixiu Liu, Nancy M. Salbach, Sandra C. Webber, Ruth Barclay

Objective

To estimate the relationships between individual and environmental variables and outdoor walking (OW) in older adults with OW limitations through verifying a conceptual model.

Methods

Baseline data from 205 older adults participating in a randomized trial of a park-based OW program were analyzed using structural equation modeling. We evaluated a three latent factor model: OW (accelerometry and self-report); individual factors (balance; leg strength; walking self-confidence, speed and endurance; mental health; education; income; car access); and environmental factors (neighbourhood walkability components).

Results

Mean age was 75 years; 73% were women. Individual factors was significantly associated with OW (β = 0.39, p p Conclusions

Better walking capacity and more confidence in the ability to walk outdoors are associated with higher OW in older adults. Better neighbourhood walkability is indirectly associated with more OW. The conceptual model demonstrates an individual and environment association; if the capacity of the individual is increased (potentially through walking interventions), they may be able to better navigate environmental challenges.

Endorsement of COVID-19 misinformation among criminal legal involved individuals in the United States: Prevalence and relationship with information sources

by Xiaoquan Zhao, Aayushi Hingle, Cameron C. Shaw, Amy Murphy, Breonna R. Riddick, Rochelle R. Davidson Mhonde, Bruce G. Taylor, Phoebe A. Lamuda, Harold A. Pollack, John A. Schneider, Faye S. Taxman

Criminal legal system involvement (CLI) is a critical social determinant of health that lies at the intersection of multiple sources of health disparities. The COVID-19 pandemic exacerbates many of these disparities, and specific vulnerabilities faced by the CLI population. This study investigated the prevalence of COVID-19-related misinformation, as well as its relationship with COVID-19 information sources used among Americans experiencing CLI. A nationally representative sample of American adults aged 18+ (N = 1,161), including a subsample of CLI individuals (n = 168), were surveyed in February-March 2021. On a 10-item test, CLI participants endorsed a greater number of misinformation statements (M = 1.88 vs. 1.27) than non-CLI participants, p

Stress appraisal in the workplace and its associations with productivity and mood: Insights from a multimodal machine learning analysis

by Mohamad Awada, Burcin Becerik Gerber, Gale M. Lucas, Shawn C. Roll

Previous studies have primarily focused on predicting stress arousal, encompassing physiological, behavioral, and psychological responses to stressors, while neglecting the examination of stress appraisal. Stress appraisal involves the cognitive evaluation of a situation as stressful or non-stressful, and as a threat/pressure or a challenge/opportunity. In this study, we investigated several research questions related to the association between states of stress appraisal (i.e., boredom, eustress, coexisting eustress-distress, distress) and various factors such as stress levels, mood, productivity, physiological and behavioral responses, as well as the most effective ML algorithms and data signals for predicting stress appraisal. The results support the Yerkes-Dodson law, showing that a moderate stress level is associated with increased productivity and positive mood, while low and high levels of stress are related to decreased productivity and negative mood, with distress overpowering eustress when they coexist. Changes in stress appraisal relative to physiological and behavioral features were examined through the lenses of stress arousal, activity engagement, and performance. An XGBOOST model achieved the best prediction accuracies of stress appraisal, reaching 82.78% when combining physiological and behavioral features and 79.55% using only the physiological dataset. The small accuracy difference of 3% indicates that physiological data alone may be adequate to accurately predict stress appraisal, and the feature importance results identified electrodermal activity, skin temperature, and blood volume pulse as the most useful physiologic features. Implementing these models within work environments can serve as a foundation for designing workplace policies, practices, and stress management strategies that prioritize the promotion of eustress while reducing distress and boredom. Such efforts can foster a supportive work environment to enhance employee well-being and productivity.

Experiences of women living with Polycystic Ovary Syndrome: A pilot case-control, single-cycle, daily Menstrual Cycle Diary study during the SARS-CoV-2 pandemic

by Kaitlin Nelson, Sonia Shirin, Dharani Kalidasan, Jerilynn C. Prior

Polycystic Ovary Syndrome (PCOS) affects many people and is often distressing. Much medical literature about diagnosis and treatment exists, but little is known about PCOS menstrual cycle-related experiences except that cycles tend to be far-apart and unpredictable. Our purpose was to examine the menstrual cycle and daily life experiences in those with PCOS having approximately month-apart cycles compared with age and BMI-matched cohort controls using data from the Menstruation & Ovulation Study 2 (MOS2) during the first 1.5 years of SARS-CoV-2 pandemic. We hypothesized that those with PCOS would experience lower self-worth and more negative moods. This is a single-cycle prospective case-control study in community-dwelling women ages 19–35 years. Eight reported physician-diagnosed PCOS and were matched (1:3 ratio) with controls by age (within .6 years) and BMI (within .19 BMI units). Experiences were recorded daily (Menstrual Cycle Diary©, Diary). All kept daily morning temperatures to assess luteal phase lengths by the validated Quantitative Basal Temperature© analysis method. From 112 in MOS2, 32 women were compared: eight with PCOS versus 24 controls. Demographic, socioeconomic, comorbidities and lifestyle variables were not different between the two groups. Cycle lengths were similar in PCOS and controls (one PCOS and control each had oligomenorrhea; most lengths were 21–35 days, P = .593). Unexpectedly, luteal phase lengths were also similar between PCOS and controls (P = .167); anovulation occurred in 5 with PCOS, and in 9 controls. There were no significant Diary differences between the two groups except for greater “outside stress” in the PCOS group (P = .020). In contrast to our hypotheses, there were no significant differences in feelings of self-worth, anxiety nor depression. The SARS-CoV-2 pandemic was a stressful time for women. MOS2 captured granular menstrual cycles, ovulation and daily experiences in women with PCOS compared with age- and BMI-matched controls. These pilot data in women with milder PCOS are the first of more research required to understand the daily experiences in those living with PCOS.

Long- versus short-duration systemic corticosteroid regimens for acute exacerbations of COPD: A systematic review and meta-analysis of randomized trials and cohort studies

by Zhen Zhao, Owen Lou, Yiyang Wang, Raymond Yin, Carrie Gong, Florence Deng, Ethan C. Wu, Jing Yi Xie, Jerry Wu, Avery Ma, Yongzhi Guo, Wei Ting Xiong

While systemic corticosteroids quicken patient recovery during acute exacerbations of COPD, they also have many adverse effects. The optimal duration of corticosteroid administration remains uncertain. We performed a systematic review and meta-analysis to compare patient outcomes between short- (≤7 days) and long- (>7 days) corticosteroid regimens in adults with acute exacerbations of COPD. MEDLINE, EMBASE, CENTRAL, and hand searches were used to identify eligible studies. Risk of bias was assessed using the Cochrane RoB 2.0 tool and ROBINS-I. Data were summarized as ORs (odds ratios) or MDs (mean differences) whenever possible and qualitatively described otherwise. A total of 11532 participants from eight RCTs and three retrospective cohort studies were included, with 1296 from seven RCTs and two cohort studies eligible for meta-analyses. Heterogeneity was present in the methodology and settings of the studies. The OR (using short duration as the treatment arm) for mortality was 0.76 (95% CI = 0.40–1.44, n = 1055). The MD for hospital length-of-stay was -0.91 days (95% CI = -1.81–-0.02 days, n = 421). The OR for re-exacerbations was 1.31 (95% CI = 0.90–1.90, n = 552). The OR for hyperglycemia was 0.90 (95% CI = 0.60–1.33, n = 423). The OR for infection incidence was 0.96 (95% CI = 0.59–1.156, n = 389). The MD for one-second forced expiratory volume change was -18.40 mL (95% CI = -111.80–75.01 mL, n = 161). The RCTs generally had low or unclear risks of bias, while the cohort studies had serious or moderate risks of bias. Our meta-analyses were affected by imprecision due to insufficient data. Some heterogeneity was present in the results, suggesting population, setting, and treatment details are potential prognostic factors. Our evidence suggests that short-duration treatments are not worse than long-duration treatments in moderate/severe exacerbations and may lead to considerably better outcomes in milder exacerbations. This supports the current GOLD guidelines. Trial registration: Our protocol is registered in PROSPERO: CRD42023374410.

Risk of sexually transmitted infections among U.S. military service members in the setting of HIV pre-exposure prophylaxis use

by Jason M. Blaylock, Evan C. Ewers, Elizabeth J. Bianchi, David B. King, Rosemary O. Casimier, Hector Erazo, Stephen Grieco, Jenny Lay, Sheila A. Peel, Kayvon Modjarrad, Charmagne G. Beckett, Jason F. Okulicz, Paul T. Scott, Shilpa Hakre

Background

The evidence for an increased incidence of sexually transmitted infections (STIs) among patients utilizing HIV pre-exposure prophylaxis (PrEP) has been inconsistent. We assessed the risk of incident STI while on PrEP compared to periods off PrEP among military service members starting PrEP.

Methods

Incidence rates of chlamydia, gonorrhea, syphilis, hepatitis C virus, and HIV were determined among military service members without HIV prescribed daily oral tenofovir disoproxil fumarate and emtricitabine for HIV PrEP from February 1, 2014 through June 10, 2016. Hazard ratios for incident STIs were calculated using an Anderson-Gill recurrent event proportional hazard regression model.

Results

Among 755 male service members, 477 (63%) were diagnosed with incident STIs (overall incidence 21.4 per 100 person-years). Male service members had a significantly lower risk of any STIs (adjusted hazard ratio (aHR) 0.21, 95% CI 0.11–0.40) while using PrEP compared to periods off PrEP after adjustment for socio-demographic characteristics, reasons for initiating PrEP, surveillance period prior to PrEP initiation, and the effect of PrEP on site and type of infection in multivariate analysis. However, when stratifying for anatomical site and type of infection, the risk of extragenital gonorrhea infection (pharyngeal NG: aHR 1.84, 95% CI 0.82–4.13, p = 0.30; rectal NG: aHR 1.23, 95% CI 0.60–2.51, p = 1.00) and extragenital CT infection (pharyngeal CT: aHR 2.30, 95% CI 0.46–11.46, p = 0.81; rectal CT: aHR 1.36, 95% CI 0.81–2.31, p = 0.66) was greater on PrEP compared to off PrEP although these values did not reach statistical significance.

Conclusions

The data suggest entry into PrEP care reduced the overall risk of STIs following adjustment for anatomical site of STI and treatment. Service members engaged in PrEP services also receive more STI prevention counseling, which might contribute to decreases in STI risk while on PrEP.

Multiocular defect in the Old English Sheepdog: A canine form of Stickler syndrome type II associated with a missense variant in the collagen-type gene <i>COL11A1</i>

by Katherine Stanbury, Renata Stavinohova, Louise Pettitt, Chris Dixon, Ellen C. Schofield, Bryan Mclaughlin, Inka Pettinen, Hannes Lohi, Sally L. Ricketts, James A. Oliver, Cathryn S. Mellersh

Multiocular defect has been described in different canine breeds, including the Old English Sheepdog. Affected dogs typically present with multiple and various ocular abnormalities. We carried out whole genome sequencing on an Old English Sheepdog that had been diagnosed with hereditary cataracts at the age of five and then referred to a board-certified veterinary ophthalmologist due to owner-reported visual deterioration. An ophthalmic assessment revealed that there was bilateral vitreal degeneration, macrophthalmos, and spherophakia in addition to cataracts. Follow-up consultations revealed cataract progression, retinal detachment, uveitis and secondary glaucoma. Whole genome sequence filtered variants private to the case, shared with another Old English Sheepdog genome and predicted to be deleterious were genotyped in an initial cohort of six Old English Sheepdogs (three affected by multiocular defect and three control dogs without evidence of inherited eye disease). Only one of the twenty-two variants segregated correctly with multiocular defect. The variant is a single nucleotide substitution, located in the collagen-type gene COL11A1, c.1775T>C, that causes an amino acid change, p.Phe1592Ser. Genotyping of an additional 14 Old English Sheepdogs affected by multiocular defect revealed a dominant mode of inheritance with four cases heterozygous for the variant. Further genotyping of hereditary cataract-affected Old English Sheepdogs revealed segregation of the variant in eight out of nine dogs. In humans, variants in the COL11A1 gene are associated with Stickler syndrome type II, also dominantly inherited.

Organisation and delivery of a dedicated multidisciplinary prone ventilation team in the intensive care unit: Strategies and lessons from COVID-19

by Luke Bracegirdle, Matthew Stubbs, Rezaur Rahman, Alexander I. R. Jackson, Helmi C. Burton-Papp, Robert Chambers, Sanjay Gupta, Michael P. W. Grocott, Ahilanandan Dushianthan

Background

COVID-19 placed immense strain on healthcare systems, necessitating innovative responses to the surge of critically ill patients, particularly those requiring mechanical ventilation. In this report, we detail the establishment of a dedicated critical care prone positioning team at University Hospital Southampton in response to escalating demand for prone positioning during the initial wave of the pandemic.

Methods

The formation of a prone positioning team involved meticulous planning and collaboration across disciplines to ensure safe and efficient manoeuvrers. A comprehensive training strategy, aligned with national guidelines, was implemented for approximately 550 staff members from a diverse background. We surveyed team members to gain insight to the lived experience.

Results

A total of 78 full-time team members were recruited and successfully executed over 1200 manoeuvres over an eight-week period. Our survey suggests the majority felt valued and expressed pride and willingness to participate again should the need arise.

Conclusion

The rapid establishment and deployment of a dedicated prone positioning team may have contributed to both patient care and staff well-being. We provide insight and lessons that may be of value for future respiratory pandemics. Future work should explore objective clinical outcomes and long-term sustainability of such services.

Dietary eating patterns, dairy consumption, and anxiety: A systematic literature review

by Naimisha Movva, Heidi Reichert, Naushin Hooda, Lauren C. Bylsma, Meghan Mitchell, Sarah S. Cohen

Background

Nutrition affects both physical and mental health but evidence is mixed regarding potential associations between anxiety and diet, particularly dairy consumption. We conducted a systematic literature review (SLR) of dairy consumption and/or various dietary patterns and risk of anxiety.

Methods

Literature searches were conducted in PubMed and Embase. All study designs except case reports, small case series, and SLRs were considered for inclusion. Reference lists of previously published SLRs were reviewed for any relevant additional studies. Studies of populations without dairy sensitivities exploring the association between dietary patterns and/or dairy consumption and anxiety published through May 2022 were identified using predefined eligibility criteria. Study quality was determined using the Academy of Nutrition and Dietetics Quality Criteria Checklist.

Results

For this SLR, 132 studies were included; 80 were cross-sectional. Studies examined different dietary patterns (e.g., Mediterranean, gluten-free) and anxiety using various anxiety scales, with 19 studies specifically reporting on whole dairy consumption and anxiety. Dairy consumption was significantly associated with a lower risk of anxiety in 7 studies, while the remaining 12 studies showed no significant associations. Evidence was mixed for the association between various dietary patterns and anxiety, but more studies observed a lower risk of anxiety with greater adherence to “healthy” diets (e.g., Mediterranean, diet quality score, vegetarian/vegan) than a higher risk. Notable heterogeneity in study populations, time periods, geographical locations, dietary assessment methods, and anxiety scales was observed.

Conclusions

The results of this SLR suggest a potential link between diet including diary consumption and anxiety, but future studies, especially with longitudinal designs that measure diet and anxiety at several timepoints and comprehensively adjust for confounders, are needed to fully understand the relationship between diet and anxiety.

Characterization of Type VI secretion system in <i>Edwardsiella ictaluri</i>

by Safak Kalindamar, Hossam Abdelhamed, Adef O. Kordon, Hasan C. Tekedar, Lesya Pinchuk, Attila Karsi

Edwardsiella ictaluri is a Gram-negative facultative intracellular fish pathogen causing enteric septicemia of catfish (ESC). While various secretion systems contribute to E. ictaluri virulence, the Type VI secretion system (T6SS) remains poorly understood. In this study, we constructed 13 E. ictaluri T6SS mutants using splicing by overlap extension PCR and characterized them, assessing their uptake and survival in channel catfish (Ictalurus punctatus) peritoneal macrophages, attachment and invasion in channel catfish ovary (CCO) cells, in vitro stress resistance, and virulence and efficacy in channel catfish. Among the mutants, EiΔevpA, EiΔevpH, EiΔevpM, EiΔevpN, and EiΔevpO exhibited reduced replication inside peritoneal macrophages. EiΔevpM, EiΔevpN, and EiΔevpO showed significantly decreased attachment to CCO cells, while EiΔevpN and EiΔevpO also displayed reduced invasion of CCO cells (p EiΔevpA, EiΔevpH, EiΔevpM, EiΔevpN, and EiΔevpO were susceptible to oxidative stress in both nutrient-rich and minimal medium. In fish challenges, EiΔevpD, EiΔevpE, EiΔevpG, EiΔevpJ, and EiΔevpK exhibited attenuation and provided effective protection against E. ictaluri wild-type (EiWT) infection in catfish fingerlings. However, their attenuation and protective efficacy were lower in catfish fry. These findings shed light on the role of the T6SS in E. ictaluri pathogenesis, highlighting its significance in intracellular survival, host cell attachment and invasion, stress resistance, and virulence. The attenuated T6SS mutants hold promise as potential candidates for protective immunization strategies in catfish fingerlings.

A high-fat and fructose diet in dogs mirrors insulin resistance and β-cell dysfunction characteristic of impaired glucose tolerance in humans

by Justin M. Gregory, Guillaume Kraft, Chiara Dalla Man, James C. Slaughter, Melanie F. Scott, Jon R. Hastings, Dale S. Edgerton, Mary C. Moore, Alan D. Cherrington

This study examined the impact of a hypercaloric high-fat high-fructose diet (HFFD) in dogs as a potential model for human impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). The HFFD not only led to weight gain but also triggered metabolic alterations akin to the precursors of human T2DM, notably insulin resistance and β-cell dysfunction. Following the HFFD intervention, the dogs exhibited a 50% decrease in insulin sensitivity within the first four weeks, paralleling observations in the progression from normal to IGT in humans. Calculations of the insulinogenic index using both insulin and C-peptide measurements during oral glucose tolerance tests revealed a significant and sustained decrease in early-phase insulin release, with partial compensation in the later phase, predominantly stemming from reduced hepatic insulin clearance. In addition, the Disposition Index, representing the β-cell’s capacity to compensate for diminished insulin sensitivity, fell dramatically. These results confirm that a HFFD can instigate metabolic changes in dogs akin to the early stages of progression to T2DM in humans. The study underscores the potential of using dogs subjected to a HFFD as a model organism for studying human IGT and T2DM.