Follow-up of women with cervical adenocarcinoma in situ treated by conization: A single centre clinical experience.

OBJECTIVE: Hysterectomy has been the historical gold standard final step in the treatment algorithm of adenocarcinoma in situ (AIS) recommended by most North American colposcopy guidelines. AIS disproportionately affects young childbearing age women, therefore a fertility sparing treatment option is desirable. Our study examines the impact of conservative treatment of AIS with conization followed by serial surveillance. METHODS: A retrospective chart review was completed of patients treated for AIS from 2006 to 2020. Charts were identified by pathologic diagnosis of AIS on cervical and uterine specimens. Charts were excluded if AIS was not treated with conization, if AIS was not confirmed on initial conization specimen, or if invasive disease was found at initial conization. RESULTS: 121 patient charts were analyzed. Median age of patients at first conization and hysterectomy was 34.8 and 40.9, respectively. First conization was by Cold Knife Cone in 58% of patients, and by Loop Electrosurgical Excisional Procedure in 42% of patients. Median follow-up period in our study was 609 days. 5% of patients had recurrence, with only one patient who recurred as cancer. One case of recurrence had a positive initial conization margin. Median time to recurrence was 700 days. 47% of patients underwent eventual hysterectomy. Residual AIS was found in 23% of hysterectomy specimens. Adenocarcinoma was diagnosed on hysterectomy specimen in four patients. CONCLUSION: Our study demonstrates the oncologic safety of treating AIS with conization and serial surveillance. Routine hysterectomy completed as a part of the AIS treatment algorithm, as in current clinical guidelines, is unnecessary.

First recorded presence of anthropogenic fly-ash particles in coral skeletons.

Fly-ash particles formed during industrial fossil-fuel combustion show a globally observed rapid increase in concentration within natural archives post-1950 and have been proposed as a marker for the Anthropocene Epoch. Here, we present the first record of fly-ash particles incorporated into coral skeletons. Particles are present in Mediterranean corals between CE 1957 and 1992 at concentrations of 8-30 g-1 coral, mirroring the period of increased industrial activity in the area, and corroborating with spheroidal carbonaceous particle (SCP) records globally. The findings have important implications for the use of SCPs as markers in natural archives. With the exception of microplastics, this is the first evidence of particulate contamination in corals collected from natural environments. Further research is needed to understand incorporation pathways into coral skeletons, any subsequent ecotoxicological impact of contaminants, and the influence on overall coral health globally.

What is the impact of antidepressant side effects on medication adherence among adult patients diagnosed with depressive disorder: A systematic review.

BACKGROUND: Medication adherence is a prerequisite to achieving beneficial treatment outcomes. In major depressive disorder, many patients fail to complete medication regimens, raising concern for poor treatment outcomes. It is usual to experience adverse drug reactions (ADRs) while taking antidepressants, and relative discomfort is reported by patients. AIMS: The present review focuses on the presence of antidepressant-related side effects and the subsequent relationship with medication non-adherence. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Following the preliminary research, the research question and eligibility criteria were created based on the PICO framework. All articles retrieved from the selected databases were exported to Covidence, a Systematic Review managing software tool. Two reviewers assessed the papers to identify the risk of bias using the Joanna Briggs Institute critical appraisal tool for cross-sectional studies. Seven studies with a low-moderate risk of bias fulfilled the eligibility criteria and were conducted from 2013 to 2020 in Europe, Africa and Asia. RESULTS: The results demonstrated high levels of suboptimal adherence ranging from 46% to 83% amongst the studied population. A variety of side effects were reported by a significant number of participants predominantly with moderate severity. A correlation between the presence of ADRs and suboptimal rates of adherence to antidepressants was found. Somnolence and headaches among other unspecified ADRs were found to increase the dropout rates for selective serotonin reuptake inhibitors. CONCLUSIONS: The present study elucidates the need for effective interventions to facilitate antidepressant adherence and enhance doctor-patient communication, benefiting both the individuals and the healthcare system and leading to better clinical outcomes and reduction of relapse-related costs.

Demonstration of chemotherapeutic mediated lymphatic changes in meningeal lymphatics in vitro, ex vivo, and in vivo.

Systemic chemotherapeutics target cancer cells but are also known to impact other cells away from the tumor. Questions remain whether systemic chemotherapy crosses the blood-brain barrier and causes inflammation in the periphery that impacts the central nervous system (CNS) downstream. The meningeal lymphatics are a critical component that drain cerebrospinal fluid from the CNS to the cervical lymph nodes for immunosurveillence. To develop new tools for understanding chemotherapy-mediated effects on the meningeal lymphatics, we present two novel models that examine cellular and tissue level changes. Our in vitro tissue engineered model of a meningeal lymphatic vessel lumen, using a simple tissue culture insert system with both lymphatic endothelial and meningeal cells, examines cell disruption. Our ex vivo model culturing mouse meningeal layers probes structural changes and remodeling, correlating to an explant tissue level. To gain a holistic understanding, we compare our in vitro and ex vivo models to in vivo studies for validation and a three-tier methodology for examining the chemotherapeutic response of the meningeal lymphatics. We have demonstrated that the meningeal lymphatics can be disrupted by systemic chemotherapy but show differential responses to platinum and taxane chemotherapies, emphasizing the need for further study of off-target impacts in the CNS.

Plant size, latitude, and phylogeny explain within-population variability in herbivory.

Interactions between plants and herbivores are central in most ecosystems, but their strength is highly variable. The amount of variability within a system is thought to influence most aspects of plant-herbivore biology, from ecological stability to plant defense evolution. Our understanding of what influences variability, however, is limited by sparse data. We collected standardized surveys of herbivory for 503 plant species at 790 sites across 116° of latitude. With these data, we show that within-population variability in herbivory increases with latitude, decreases with plant size, and is phylogenetically structured. Differences in the magnitude of variability are thus central to how plant-herbivore biology varies across macroscale gradients. We argue that increased focus on interaction variability will advance understanding of patterns of life on Earth.

Antibiotic resistance genes in the gut microbiota of mothers and linked neonates with or without sepsis from low- and middle-income countries.

Early development of the microbiome has been shown to affect general health and physical development of the infant and, although some studies have been undertaken in high-income countries, there are few studies from low- and middle-income countries. As part of the BARNARDS study, we examined the rectal microbiota of 2,931 neonates (term used up to 60 d) with clinical signs of sepsis and of 15,217 mothers screening for blaCTX-M-15, blaNDM, blaKPC and blaOXA-48-like genes, which were detected in 56.1%, 18.5%, 0% and 4.1% of neonates' rectal swabs and 47.1%, 4.6%, 0% and 1.6% of mothers' rectal swabs, respectively. Carbapenemase-positive bacteria were identified by MALDI-TOF MS and showed a high diversity of bacterial species (57 distinct species/genera) which exhibited resistance to most of the antibiotics tested. Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae/E. cloacae complex, the most commonly found isolates, were subjected to whole-genome sequencing analysis and revealed close relationships between isolates from different samples, suggesting transmission of bacteria between neonates, and between neonates and mothers. Associations between the carriage of antimicrobial resistance genes (ARGs) and healthcare/environmental factors were identified, and the presence of ARGs was a predictor of neonatal sepsis and adverse birth outcomes.

Advancing our understanding of skeletal muscle across the lifecourse: Protocol for the MASS_Lifecourse study and characteristics of the first 80 participants.

INTRODUCTION: Sarcopenia, the age-related loss of skeletal muscle strength and mass, carries a significant burden for affected individuals. There has been little investigation of sarcopenia using experimental medicine techniques to study human muscle tissue in detail. The aim of the Muscle Ageing Sarcopenia Studies Lifecourse (MASS_Lifecourse) study is to recruit up to 160 participants, equally divided between females and males between ages 45 and 85 years for detailed phenotyping of skeletal muscle health. Here we describe the protocol for the study and the characteristics of the first 80 participants. METHODS: We are recruiting participants from three sources in the north-east of England. Study fieldwork comprises a home visit (or videocall) for consent and assessment of health, cognition, lifestyle, and wellbeing. This is followed by a visit to a clinical research facility for assessment of sarcopenia status and collection of samples including a vastus lateralis muscle biopsy. We produced descriptive statistics for the first 80 participants, including expressing their grip strength relative to normative data in the form of Z-scores. RESULTS: The first 80 participants (53.8 % female) covered the target ages, ranging from 48 to 84 years. They were regularly physically active, reported good physical function and had a prevalence of sarcopenia (including probable sarcopenia) of 11.3 % based on the revised European consensus. Their grip strength was similar to that in the general population, with a mean Z-score of 0.09 standard deviations (95 % CI: -1.64, 1.83) above that expected. CONCLUSIONS: The MASS_Lifecourse study combines comprehensive health and lifestyle data with a range of biological samples including skeletal muscle. The findings from planned analyses should contribute to improvements in the diagnosis, treatment, and prevention of sarcopenia.

The P4 study: Subsequent pregnancy maternal physiology after hypertensive and normotensive pregnancies.

OBJECTIVES: Hypertensive disorders of pregnancy are associated with subsequent increased risk of cardiometabolic disease. Adverse cardiometabolic measures are noted soon after hypertensive versus normotensive pregnancy (NP); to what degree these persist into a subsequent pregnancy (SP) is unknown. This study aimed to assess women's physiology early in SP after hypertensive pregnancy (HP: preeclampsia or gestational hypertension) or NP and compare SP to 6 months postpartum findings from the index pregnancy. STUDY DESIGN: Prospective sub-study of the P4 (Postpartum, Physiology, Psychology and Paediatric) observational cohort. Measurements six months after NP versus HP, and the SP at 11-13 weeks gestation. MAIN OUTCOME MEASURES: Blood pressure (BP), blood and urine tests (urine ACR, HOMA-IR, LDL cholesterol), body composition, and contribution of maternal characteristics and inter-pregnancy factors to BP and body fat (FM%) in SP. RESULTS: 49 women (34 NP, 15 HP). In the SP, post-HP women had higher BP (112/70 mmHg HP vs 102/64 mmHg NP; p < .001), with no significant drop from six months postpartum to early SP. On regression analysis, systolic and diastolic BP at 6-months were the major predictors for SP systolic (p < 0.001) and diastolic (p = 0.009) BP respectively in the SP. Longer interpregnancy interval and increased FM% 6-months postpartum were associated with higher SP FM% (p < 0.001). CONCLUSIONS: BP and body fat six months postpartum were similar early in the SP for HP group, and postpartum BP and FM% were major predictors of their corresponding SP measurements. Postpartum/inter-pregnancy intervention programs to improve these cardiometabolic risk markers might help improve women's long-term health and require investigation.

Exit strategies: optimising feasible surveillance for detection, elimination, and ongoing prevention of COVID-19 community transmission.

BACKGROUND: Following implementation of strong containment measures, several countries and regions have low detectable community transmission of COVID-19. We developed an efficient, rapid, and scalable surveillance strategy to detect remaining COVID-19 community cases through exhaustive identification of every active transmission chain. We identified measures to enable early detection and effective management of any reintroduction of transmission once containment measures are lifted to ensure strong containment measures do not require reinstatement. METHODS: We compared efficiency and sensitivity to detect community transmission chains through testing of the following: hospital cases; fever, cough and/or ARI testing at community/primary care; and asymptomatic testing; using surveillance evaluation methods and mathematical modelling, varying testing capacities, reproductive number (R) and weekly cumulative incidence of COVID-19 and non-COVID-19 respiratory symptoms using data from Australia. We assessed system requirements to identify all transmission chains and follow up all cases and primary contacts within each chain, per million population. RESULTS: Assuming 20% of cases are asymptomatic and 30% of symptomatic COVID-19 cases present for testing, with R = 2.2, a median of 14 unrecognised community cases (8 infectious) occur when a transmission chain is identified through hospital surveillance versus 7 unrecognised cases (4 infectious) through community-based surveillance. The 7 unrecognised community upstream cases are estimated to generate a further 55-77 primary contacts requiring follow-up. The unrecognised community cases rise to 10 if 50% of cases are asymptomatic. Screening asymptomatic community members cannot exhaustively identify all cases under any of the scenarios assessed. The most important determinant of testing requirements for symptomatic screening is levels of non-COVID-19 respiratory illness. If 4% of the community have respiratory symptoms, and 1% of those with symptoms have COVID-19, exhaustive symptomatic screening requires approximately 11,600 tests/million population using 1/4 pooling, with 98% of cases detected (2% missed), given 99.9% sensitivity. Even with a drop in sensitivity to 70%, pooling was more effective at detecting cases than individual testing under all scenarios examined. CONCLUSIONS: Screening all acute respiratory disease in the community, in combination with exhaustive and meticulous case and contact identification and management, enables appropriate early detection and elimination of COVID-19 community transmission. An important component is identification, testing, and management of all contacts, including upstream contacts (i.e. potential sources of infection for identified cases, and their related transmission chains). Pooling allows increased case detection when testing capacity is limited, even given reduced test sensitivity. Critical to the effectiveness of all aspects of surveillance is appropriate community engagement, messaging to optimise testing uptake and compliance with other measures.

Maternal macro- and micronutrient intake six months after hypertensive versus normotensive pregnancy: is poor diet quality contributing to future cardiometabolic disease risk?

BACKGROUND: Hypertensive pregnancy is associated with increased long-term cardiometabolic disease risk. Assessing dietary intake patterns after hypertensive (HP) versus normotensive pregnancy (NP) may provide insights into the mechanism of this risk. METHODS: This study was a prospective sub-study of the P4 (Postpartum, Physiology, Psychology and Paediatrics) cohort. Women were studied six months after NP versus HP (preeclampsia or gestational hypertension). Dietary energy, macronutrient and micronutrient intake were measured using a three-day food diary (FoodWorks™) and assessed against Australian and New Zealand Nutrient Reference Values to determine nutritional adequacy. Comparisons between breastfeeding and non-breastfeeding women were assessed, and linear regression modelling (using hypertensive status, breastfeeding status, and demographic/pregnancy variables) performed to assess predictors of energy intake. RESULTS: Seventy-four women (60 NP, 14 HP) were included. HP women had higher mean body mass index (p = 0.02) and lower breastfeeding rates (29% HP versus 83% NP, p < 0.001) compared to NP women. Twenty-four-hour energy intake and total fat intake were 17% and 20% lower after HP respectively. Nutrient deficiencies were prevalent across all participants, however more HP women had inadequate magnesium, calcium and phosphorus intake. Breastfeeding women had significantly increased energy (17%), carbohydrate (15%) and total fat intake (21%), and increased vitamin A, vitamin E, riboflavin, magnesium and iron intake compared to non-breastfeeding women. HP and breastfeeding status were independent predictors of energy intake. CONCLUSIONS: HP women had lower micronutrient intake and greater prevalence of nutritional inadequacy compared to NP women, reflecting poorer diet quality and potentially contributing to future increased cardiometabolic disease risk.

Association Between Minimum Inhibitory Concentration, Beta-lactamase Genes and Mortality for Patients Treated With Piperacillin/Tazobactam or Meropenem From the MERINO Study.

INTRODUCTION: This study aims to assess the association of piperacillin/tazobactam and meropenem minimum inhibitory concentration (MIC) and beta-lactam resistance genes with mortality in the MERINO trial. METHODS: Blood culture isolates from enrolled patients were tested by broth microdilution and whole genome sequencing at a central laboratory. Multivariate logistic regression was performed to account for confounders. Absolute risk increase for 30-day mortality between treatment groups was calculated for the primary analysis (PA) and the microbiologic assessable (MA) populations. RESULTS: In total, 320 isolates from 379 enrolled patients were available with susceptibility to piperacillin/tazobactam 94% and meropenem 100%. The piperacillin/tazobactam nonsusceptible breakpoint (MIC >16 mg/L) best predicted 30-day mortality after accounting for confounders (odds ratio 14.9, 95% confidence interval [CI] 2.8-87.2). The absolute risk increase for 30-day mortality for patients treated with piperacillin/tazobactam compared with meropenem was 9% (95% CI 3%-15%) and 8% (95% CI 2%-15%) for the original PA population and the post hoc MA populations, which reduced to 5% (95% CI -1% to 10%) after excluding strains with piperacillin/tazobactam MIC values >16 mg/L. Isolates coharboring extended spectrum ß-lactamase (ESBL) and OXA-1 genes were associated with elevated piperacillin/tazobactam MICs and the highest risk increase in 30-day mortality of 14% (95% CI 2%-28%). CONCLUSIONS: After excluding nonsusceptible strains, the 30-day mortality difference from the MERINO trial was less pronounced for piperacillin/tazobactam. Poor reliability in susceptibility testing performance for piperacillin/tazobactam and the high prevalence of OXA coharboring ESBLs suggests that meropenem remains the preferred choice for definitive treatment of ceftriaxone nonsusceptible Escherichia coli and Klebsiella.

Delivering remote consultations: Talking the talk.

INTRODUCTION: There is an increasing affinity for remote health consultations (including telephone and virtual platforms), enabling new models of accessing services to evolve. Whilst many key skills are transferable from traditional to remote consultations, there is even greater emphasis on verbal communication skills during these interactions. PURPOSE: This masterclass considers the communication skills required for delivering remote health care consultations, in particular focussing on: 12 interactional features in an opening sequence of a remote call; active listening; how to offer advice using the Ask-Offer-Ask framework; and subtleties in phrasing and prosody when closing a call that may indicate a level of satisfaction (or otherwise). IMPLICATIONS: In planning for digitally-enabled services to become mainstream, the differences in communication between remote and face-to-face consultations must be recognised and embraced.

Provincial Veterinary Services respond to drought in South Africa.

In 2018, Cape Town, South Africa, nearly ran out of water. That this has not yet happened is in large part due to the water-saving efforts of its citizens. It is highly likely that this situation will be repeated in Cape Town and that similar situations will be experienced by major cities in other parts of the world. Efforts to save water should thus continue and the lessons learned in Cape Town should be shared. The functioning of Veterinary Services during a drought is affected in the same way as any business, in terms of running an office, but veterinary professionals face an increased risk of exposure to pathogens, compared to that of many occupations, and of veterinary officials becoming disease vectors. One component of Veterinary Services is veterinary laboratory services. Laboratory procedures rely heavily on water and, without advance planning, a laboratory's function can be severely limited by a restricted water supply. In many cases, innovative water-saving techniques can be used to reduce water use substantially without compromising the quality of the services offered. Here, the authors share their experiences and some lessons learned while working in Veterinary Services in the Western Cape province of South Africa.

En 2018, la ville du Cap en Afrique du Sud a failli manquer d'eau. Si la pénurie totale a pu être évitée, ce fut en grande partie grâce aux efforts déployés par les habitants pour économiser l'eau. Or, il est très probable que cette situation se reproduise au Cap et que des situations analogues surviennent dans nombre de grandes métropoles d'autres régions du monde. C'est pourquoi il convient de poursuivre les efforts d'économie d'eau et de partager avec d'autres les enseignements tirés dans la ville du Cap. L'impact de la sécheresse sur le fonctionnement des Services vétérinaires est similaire à celui de toute organisation en termes de gestion administrative ; en revanche, par rapport à d'autres professionnels, les vétérinaires de terrain sont davantage exposés à des agents pathogènes et au risque de devenir eux-mêmes vecteurs de maladies. Les laboratoires vétérinaires sont l'une des composantes des Services vétérinaires. Les procédures de laboratoire sont amplement tributaires de l'eau ; or, en l'absence d'une planification préalable, les activités d'un laboratoire pourraient être gravement mises à mal par des restrictions de l'approvisionnement en eau. Dans bien des cas, il est possible d'utiliser des techniques innovantes pour économiser l'eau afin d'en diminuer la consommation sans pour autant compromettre la qualité des services rendus. Les auteurs font part de leur expérience et de certains enseignements tirés lorsqu'ils travaillaient dans les Services vétérinaires de la province du Cap-Occidental en Afrique du Sud.

En 2018 faltó poco para que Ciudad del Cabo (Sudáfrica) se quedara sin agua. Si las cosas aún no han llegado a este extremo es, en gran parte, gracias a los esfuerzos de los habitantes por economizar agua. Es muy probable que en el futuro Ciudad del Cabo vuelva a sufrir esta situación y que grandes metrópolis de otras partes del mundo conozcan dificultades parecidas. Por ello hay que perseverar en los esfuerzos de ahorro de agua y se deben compartir las enseñanzas extraídas en Ciudad del Cabo. Durante una sequía, el funcionamiento de los Servicios Veterinarios se ve afectado del mismo modo que cualquier otra actividad, por lo que respecta al trabajo de oficina, pero además los profesionales del ramo, en comparación con los de otros muchos sectores, corren mayor peligro de exposición a patógenos, lo que a su vez entraña el riesgo de que los propios veterinarios ejerzan de vectores de la enfermedad. Uno de los puntales de los Servicios Veterinarios son los laboratorios veterinarios, cuyo quehacer depende en gran medida del uso de agua. Por ello, cuando no se ha planificado con antelación la eventualidad de una penuria de agua, esta puede imponer graves cortapisas a las funciones de laboratorio. En muchos casos es posible emplear innovadoras técnicas de ahorro de agua para reducir sustancialmente las cantidades utilizadas sin menoscabo de la calidad de los servicios dispensados. Los autores comparten su experiencia y algunas de las lecciones que extrajeron de su trabajo en los Servicios Veterinarios de la provincia sudafricana del Cabo Occidental.

Mitochondrial Isolevuglandins Contribute to Vascular Oxidative Stress and Mitochondria-Targeted Scavenger of Isolevuglandins Reduces Mitochondrial Dysfunction and Hypertension.

Hypertension remains a major health problem in Western Societies, and blood pressure is poorly controlled in a third of patients despite use of multiple drugs. Mitochondrial dysfunction contributes to hypertension, and mitochondria-targeted agents can potentially improve treatment of hypertension. We have proposed that mitochondrial oxidative stress produces reactive dicarbonyl lipid peroxidation products, isolevuglandins, and that scavenging of mitochondrial isolevuglandins improves vascular function and reduces hypertension. To test this hypothesis, we have studied the accumulation of mitochondrial isolevuglandins-protein adducts in patients with essential hypertension and Ang II (angiotensin II) model of hypertension using mass spectrometry and Western blot analysis. The therapeutic potential of targeting mitochondrial isolevuglandins was tested by the novel mitochondria-targeted isolevuglandin scavenger, mito2HOBA. Mitochondrial isolevuglandins in arterioles from hypertensive patients were 250% greater than in arterioles from normotensive subjects, and ex vivo mito2HOBA treatment of arterioles from hypertensive subjects increased deacetylation of a key mitochondrial antioxidant, SOD2 (superoxide dismutase 2). In human aortic endothelial cells stimulated with Ang II plus TNF (tumor necrosis factor)-α, mito2HOBA reduced mitochondrial superoxide and cardiolipin oxidation, a specific marker of mitochondrial oxidative stress. In Ang II-infused mice, mito2HOBA diminished mitochondrial isolevuglandins-protein adducts, raised Sirt3 (sirtuin 3) mitochondrial deacetylase activity, reduced vascular superoxide, increased endothelial nitric oxide, improved endothelium-dependent relaxation, and attenuated hypertension. Mito2HOBA preserved mitochondrial respiration, protected ATP production, and reduced mitochondrial permeability pore opening in Ang II-infused mice. These data support the role of mitochondrial isolevuglandins in endothelial dysfunction and hypertension. We conclude that scavenging of mitochondrial isolevuglandins may have therapeutic potential in treatment of vascular dysfunction and hypertension.

Scavenging of reactive dicarbonyls with 2-hydroxybenzylamine reduces atherosclerosis in hypercholesterolemic Ldlr-/- mice.

Lipid peroxidation generates reactive dicarbonyls including isolevuglandins (IsoLGs) and malondialdehyde (MDA) that covalently modify proteins. Humans with familial hypercholesterolemia (FH) have increased lipoprotein dicarbonyl adducts and dysfunctional HDL. We investigate the impact of the dicarbonyl scavenger, 2-hydroxybenzylamine (2-HOBA) on HDL function and atherosclerosis in Ldlr-/- mice, a model of FH. Compared to hypercholesterolemic Ldlr-/- mice treated with vehicle or 4-HOBA, a nonreactive analogue, 2-HOBA decreases atherosclerosis by 60% in en face aortas, without changing plasma cholesterol. Ldlr-/- mice treated with 2-HOBA have reduced MDA-LDL and MDA-HDL levels, and their HDL display increased capacity to reduce macrophage cholesterol. Importantly, 2-HOBA reduces the MDA- and IsoLG-lysyl content in atherosclerotic aortas versus 4-HOBA. Furthermore, 2-HOBA reduces inflammation and plaque apoptotic cells and promotes efferocytosis and features of stable plaques. Dicarbonyl scavenging with 2-HOBA has multiple atheroprotective effects in a murine FH model, supporting its potential as a therapeutic approach for atherosclerotic cardiovascular disease.

Professional and interprofessional identities: a scoping review.

Identity development within the interprofessional field is an emerging area of research. This scoping review aims to establish how professional and interprofessional identities are defined, conceptualized, theorized and measured within the interprofessional literature. Six databases were systematically searched for papers focusing on professional and/or interprofessional identities in interprofessional healthcare and education using a scoping review methodology. A total of 84 papers were included. Most papers discussed professional identity only; the minority discussed both identities. There were three key findings. First, no universal definition of interprofessional identity exists. Second, there is no shared understanding of interprofessional identity and its relationship with professional identity. Third, poor alignment between definitions, conceptualizations, theories and measures of interprofessional identity exists. The absence of a psychometrically robust instrument that specifically measures interprofessional identity and the short-term focus of current interprofessional identity research further limits understanding. Research that critically examines professional and interprofessional identity development should be underpinned by clear definitions, concepts, theories and measures of both identities. High-quality research will allow greater understanding of interprofessional identity development and its impact on interprofessional practice.

Safety, tolerability, and pharmacokinetics of repeated oral doses of 2-hydroxybenzylamine acetate in healthy volunteers: a double-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: 2-Hydroxybenzylamine (2-HOBA) is a selective dicarbonyl electrophile scavenger being developed as a nutritional supplement to help protect against the development of conditions associated with dicarbonyl electrophile formation, such as the cognitive decline observed with Mild Cognitive Impairment or Alzheimer's disease. METHODS: This study evaluated the safety, tolerability, and pharmacokinetics of repeated oral doses of 2-HOBA acetate (500 or 750 mg) administered to healthy volunteers every eight hours for two weeks. The effects of 2-HOBA on cyclooxygenase function and cerebrospinal fluid penetrance of 2-HOBA were also investigated. RESULTS: Repeated oral administration of 2-HOBA was found to be safe and well-tolerated up to 750 mg TID for 15 days. 2-HOBA was absorbed within 2 h of administration, had a half-life of 2.10-3.27 h, and an accumulation ratio of 1.38-1.52. 2-HOBA did not interfere with cyclooxygenase function and was found to be present in cerebrospinal fluid 90 min after dosing. CONCLUSIONS: Repeated oral administration of 2-HOBA was found to be safe and well-tolerated. These results support continued development of 2-HOBA as a nutritional supplement. TRIAL REGISTRATION: Studies are registered at ClinicalTrials.gov (NCT03555682 Registered 13 June 2018, NCT03554096 Registered 12 June 18).