Tropoelastin Improves Post-Infarct Cardiac Function.

BACKGROUND: Myocardial infarction (MI) is among the leading causes of death worldwide. Following MI, necrotic cardiomyocytes are replaced by a stiff collagen-rich scar. Compared to collagen, the extracellular matrix protein elastin has high elasticity and may have more favorable properties within the cardiac scar. We sought to improve post-MI healing by introducing tropoelastin, the soluble subunit of elastin, to alter scar mechanics early after MI. METHODS AND RESULTS: We developed an ultrasound-guided direct intramyocardial injection method to administer tropoelastin directly into the left ventricular anterior wall of rats subjected to induced MI. Experimental groups included shams and infarcted rats injected with either PBS vehicle control or tropoelastin. Compared to vehicle treated controls, echocardiography assessments showed tropoelastin significantly improved left ventricular ejection fraction (64.7±4.4% versus 46.0±3.1% control) and reduced left ventricular dyssynchrony (11.4±3.5 ms versus 31.1±5.8 ms control) 28 days post-MI. Additionally, tropoelastin reduced post-MI scar size (8.9±1.5% versus 20.9±2.7% control) and increased scar elastin (22±5.8% versus 6.2±1.5% control) as determined by histological assessments. RNA sequencing (RNAseq) analyses of rat infarcts showed that tropoelastin injection increased genes associated with elastic fiber formation 7 days post-MI and reduced genes associated with immune response 11 days post-MI. To show translational relevance, we performed immunohistochemical analyses on human ischemic heart disease cardiac samples and showed an increase in tropoelastin within fibrotic areas. Using RNA-seq we also demonstrated the tropoelastin gene ELN is upregulated in human ischemic heart disease and during human cardiac fibroblast-myofibroblast differentiation. Furthermore, we showed by immunocytochemistry that human cardiac fibroblast synthesize increased elastin in direct response to tropoelastin treatment. CONCLUSIONS: We demonstrate for the first time that purified human tropoelastin can significantly repair the infarcted heart in a rodent model of MI and that human cardiac fibroblast synthesize elastin. Since human cardiac fibroblasts are primarily responsible for post-MI scar synthesis, our findings suggest exciting future clinical translation options designed to therapeutically manipulate this synthesis.

Cardiovascular Risk Factors and Disparities in Management of Embolic Stroke: A Western Sydney Perspective.

BACKGROUND: Ischaemic stroke remains one of the leading causes of death and disability worldwide. The population of Western Sydney has a unique demographic with lower socioeconomic status and a culturally and linguistically diverse population. This study aims to investigate the demographics and cardiovascular risk factors of patients in Western Sydney, focusing on the prevalence and profile of cardioembolic (CE) strokes and embolic strokes of undetermined source (ESUS). METHOD: Prospective data were collected in 463 patients with ischaemic stroke presenting to a tertiary centre in Western Sydney, who underwent predischarge transthoracic echocardiography. Patients with haemorrhagic strokes or unclear stroke diagnosis were excluded. Analysis of stroke subtype (CE, ESUS, or non-embolic) and clinical characteristics was performed based on age, gender, and prior atrial fibrillation (AF) prevalence. RESULTS: Of the 463 patients, 147 (32%) had CE strokes, and 147 (32%) had ESUS. Cardioembolic (CE) strokes were associated with older age (≥65 years) and a history of congestive cardiac failure. Older patients had higher rates of hypertension, ischaemic heart disease, AF, and congestive heart failure. History of AF was present in 67 patients (14.5%); however, only 51% received anticoagulation before admission despite a low bleeding risk. The transthoracic echocardiography characteristics of ESUS/non-embolic strokes differed from those of CE strokes; 20% of patients with ESUS had an enlarged left atrium, suggesting a subset of patients with ESUS with a left atrial myopathy. CONCLUSIONS: Patients with ischaemic stroke in Western Sydney have a high prevalence of cardiovascular risk factors which were often undertreated. Half of the patients with prior AF did not receive anticoagulation despite low bleeding risk, indicating a gap in optimal stroke prevention. There were distinct echocardiographic characteristics among stroke subtypes. Further analysis of left atrium parameters may provide greater insights into the pathogenesis and prevention of embolic strokes.

Systemic lupus erythematosus associated with development of macrophage activation syndrome and disseminated aspergillosis.

PURPOSE: Macrophage activation syndrome (MAS) is a rare illness, especially in critically ill adults. The diagnosis of MAS is challenging, requiring the expertise of multiple specialists, and treatments for MAS can be associated with catastrophic complications. CLINICAL FEATURES: We describe the case of a 31-yr-old Vietnamese student who was diagnosed with cutaneous systemic lupus erythematosus (SLE) in November 2020 and was initiated on treatment with low-dose corticosteroids and hydroxychloroquine as an outpatient. Ten days later, she presented to hospital with decreased consciousness, fever, periorbital swelling, and hypotension necessitating intubation. Computed tomography angiography (CTA) and lumbar puncture did not show a stroke or central nervous system infection. Serology and clinical presentation were consistent with MAS. She was initially treated with 4.5 g pulse methylprednisolone and subsequently with the interleukin-1 receptor antagonist, anakinra, and maintenance corticosteroids because of persistently elevated inflammatory markers. Her intensive care unit stay was complicated by aspiration, airway obstruction due to fungal tracheobronchitis necessitating extracorporeal membrane oxygenation (ECMO), and ring-enhancing cerebral lesions, and, ultimately, massive hemoptysis resulting in death. CONCLUSIONS: Four features of this case merit discussion, including the: 1) infrequent association of SLE with MAS; 2) short interval between SLE diagnosis and critical illness; 3) manifestation of fungal tracheobronchitis with airway obstruction; and 4) lack of response to antifungal treatment while receiving ECMO.

RéSUMé: OBJECTIF: Le syndrome d'activation macrophagique (SAM) est une maladie rare, en particulier chez les adultes gravement malades. Le diagnostic d'un SAM est difficile à poser, nécessitant l'expertise de plusieurs spécialistes, et les traitements de ce syndrome peuvent être associés à des complications catastrophiques. CARACTéRISTIQUES CLINIQUES: Nous décrivons le cas d'une étudiante vietnamienne de 31 ans ayant reçu un diagnostic de lupus érythémateux disséminé (LED) cutané en novembre 2020; un traitement par corticostéroïdes à faible dose et hydroxychloroquine a été amorcé en ambulatoire. Dix jours plus tard, elle s'est présentée à l'hôpital avec une diminution de la conscience, de la fièvre, un gonflement périorbitaire et une hypotension nécessitant une intubation. L'angiographie par tomodensitométrie et la ponction lombaire n'ont pas révélé d'accident vasculaire cérébral ou d'infection du système nerveux central. La sérologie et la présentation clinique correspondaient à celles d'un SAM. Elle a d'abord été traitée avec 4,5 g de méthylprednisolone en injection ponctuelle, puis avec un antagoniste du récepteur à l'interleukine-1, l'anakinra et des corticostéroïdes d'entretien en raison de marqueurs inflammatoires élevés persistants. Son séjour en soins intensifs a été compliqué par une aspiration, une obstruction des voies aériennes due à une trachéobronchite fongique nécessitant une oxygénation par membrane extracorporelle (ECMO) et des lésions cérébrales avec rehaussement en anneau, et finalement une hémoptysie massive entraînant la mort. CONCLUSION: Quatre caractéristiques de ce cas méritent d'être discutées, soit: 1) l'association peu fréquente du lupus érythémateux disséminé avec un syndrome d'activation macrophagique; 2) le court intervalle entre le diagnostic de LED et la maladie grave; 3) l'apparition d'une trachéobronchite fongique avec obstruction des voies aériennes; et 4) l'absence de réponse au traitement antifongique pendant le traitement par ECMO.

Von Willebrand factor assays in patients with acquired immune thrombotic thrombocytopenia purpura treated with caplacizumab.

Acquired immune thrombotic thrombocytopenic purpura (iTTP) is a rare disease with a poor prognosis if undiagnosed. It is caused by autoantibody production to the von Willebrand factor (VWF) cleaving protease, A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). Caplacizumab, an immunoglobulin directed to the platelet glycoprotein Ibα receptor of VWF, has been reported to induce quicker resolution of iTTP compared to placebo. The laboratory measurement of VWF activity was significantly reduced in clinical trials of caplacizumab. Several VWF assays are available in the UK and this study investigated whether differences in VWF parameters were present in 11 patients diagnosed with iTTP and treated with daily caplacizumab. Chromogenic factor VIII activity, VWF antigen, collagen binding activity, VWF multimers and six VWF activity assays were measured prior to caplacizumab therapy and on several occasions during treatment. VWF antigen and collagen binding activity levels were normal or borderline normal in all patients. Ultra-large molecular weight multimers were present in all patients following treatment. VWF activity assays were normal or reduced during treatment, but this was reagent and patient dependant. In the unusual scenario of a caplacizumab-treated patient requiring measurement of VWF activity, it is important that laboratories understand how their local reagents perform as results cannot be predicted.

The predictive value of patient, therapist, and in-session ratings of motivational factors early in remote cognitive behavioural therapy for severe health anxiety.

OBJECTIVES: Remote psychotherapy and the prevalence of Severe Health Anxiety (SHA) are both growing as a result of the COVID-19 pandemic. Remotely delivered Cognitive Behavioural Therapy (rCBT) for SHA is evidenced as effective, but many who seek help do not benefit. Motivational processes can influence outcomes, but it is unclear what assessment methods offer the best clinical utility in rCBT for SHA. DESIGN: This study compared the predictive validity of patient, therapist and in-session ratings of motivational factors taken at session two of rCBT for SHA among high healthcare users experiencing multimorbidity. METHODS: Motivational factors were assessed for 56 participants who attended at least two sessions of CBT for SHA delivered via video-conferencing or telephone. Following session two, therapists and patients completed online assessments of patient motivation. Two trained observers also rated motivational factors and therapeutic alliance from in-session interactions using session two recordings and transcripts. Multilevel modelling was used to predict health anxiety and a range of secondary health outcomes from motivation assessments. RESULTS: Where patients were more actively engaged in discussion of positive changes during session two, greater outcome improvements ensued in health anxiety and all secondary outcomes. Conversely, larger proportions of session two spent describing problems predicted poorer outcomes. Therapist and patient assessments of motivation did not predict health anxiety, but therapist assessments of client confidence and motivation predicted all secondary outcomes. CONCLUSIONS: Motivation remains an important process in CBT when delivered remotely, and motivational factors may predict outcomes more consistently from in-session interactions, compared to self-reports.

Substance Use in Relation to Mental Illness: A Study of Mexican-Origin Latinos with Schizophrenia and Their Family Members.

Little is known about family context and substance use behaviors among Latinos with schizophrenia. Learning about patient and family caregiver perceptions of use is critical to our understanding of how best to support these vulnerable patients and family caregivers. This study explored perceptions of substance use in relation to mental illness among Latinos primarily of Mexican origin with schizophrenia and their family caregivers. Semistructured interviews were conducted with 34 participants (20 family caregivers; 14 patients) with direct and indirect substance use experience, in their preferred language. Data were analyzed using thematic analysis, which consisted of comparing codes across and within patient and family caregiver transcripts. Findings revealed that substance use affected well-being, particularly patient recovery and caregiver burden. Strategies to address well-being included limiting substance use, being vigilant about patient use, and communicating the negative impact of use. The environmental impact and stigma of substance use were major contextual challenges. Patients addressed these by limiting their socialization. Family social context was important to how substance use was perceived and managed by patients and caregivers. As such, treatment models should consider a holistic perspective that incorporates family context when addressing substance use among Latinos with schizophrenia.

Pluripotent stem cell-derived mesenchymal stromal cells improve cardiac function and vascularity after myocardial infarction.

BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) have been shown to improve cardiac function after injury and are the subject of ongoing clinical trials. In this study, the authors tested the cardiac regenerative potential of an induced pluripotent stem cell-derived MSC (iPSC-MSC) population (Cymerus MSCs) in a rat model of myocardial ischemia-reperfusion (I/R). Furthermore, the authors compared this efficacy with bone marrow-derived MSCs (BM-MSCs), which are the predominant cell type in clinical trials. METHODS: Four days after myocardial I/R injury, rats were randomly assigned to (i) a Cymerus MSC group (n = 15), (ii) a BM-MSC group (n = 15) or (iii) a vehicle control group (n = 14). For cell-treated animals, a total of 5 × 106 cells were injected at three sites within the infarcted left ventricular (LV) wall. RESULTS: One month after cell transplantation, Cymerus MSCs improved LV function (assessed by echocardiography) compared with vehicle and BM-MSCs. Interestingly, Cymerus MSCs enhanced angiogenesis without sustained engraftment or significant impact on infarct scar size. Suggesting safety, Cymerus MSCs had no effect on inducible tachycardia or the ventricular scar heterogeneity that provides a substrate for cardiac re-entrant circuits. CONCLUSIONS: The authors here demonstrate that intra-myocardial administration of iPSC-MSCs (Cymerus MSCs) provide better therapeutic effects compared with conventional BM-MSCs in a rodent model of myocardial I/R. Because of its manufacturing scalability, iPSC-MSC therapy offers an exciting opportunity for an "off-the-shelf" stem cell therapy for cardiac repair.

Improving natural product research translation: From source to clinical trial.

While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety and efficacy, CTs, especially phase III CTs, are costly and require rigorous planning to optimize the value of the information obtained. More effective bridging from NP research to CT was the goal of a September, 2018 transdisciplinary workshop. Participants emphasized that replicability and likelihood of successful translation depend on rigor in experimental design, interpretation, and reporting across the continuum of NP research. Discussions spanned good practices for NP characterization and quality control; use and interpretation of models (computational through in vivo) with strong clinical predictive validity; controls for experimental artefacts, especially for in vitro interrogation of bioactivity and mechanisms of action; rigorous assessment and interpretation of prior research; transparency in all reporting; and prioritization of research questions. Natural product clinical trials prioritized based on rigorous, convergent supporting data and current public health needs are most likely to be informative and ultimately affect public health. Thoughtful, coordinated implementation of these practices should enhance the knowledge gained from future NP research.

Predicting outcomes and sudden gains from initial in-session interactions during remote cognitive-behavioural therapy for severe health anxiety.

There has been a dramatic increase in remote psychotherapy since the onset of the COVID-19 crisis. There is also expected to be an increase in mental health problems in the wake of the COVID-19 pandemic. An increase in severe health anxiety (SHA) is particularly anticipated, for which cognitive-behavioural therapy (CBT) is a frontline treatment. However, it is unclear what interaction types are associated with outcome-improvement in remote-CBT (rCBT) for SHA. This study aimed to identify interaction types that predict outcomes and sudden gains in rCBT for SHA using initial therapy session content. Forty-eight participants in rCBT for SHA had interactions at their first sessions categorized and rated in terms of patient activation: an individual's confidence and ability to manage their health. Multilevel modelling assessed whether early interaction types predicted session-by-session wellbeing. For participants experiencing sudden gains (n = 12) interactions at the session directly prior to the gain were similarly categorized and rated. The scores were then compared with ratings for the preceding session. A smaller proportion of early sessions was taken up with problem descriptions among those with greater outcome improvements. There was also a significant reduction in the proportion of the session spent describing problems in the session directly prior to a sudden gain, as compared with the previous session. Conversely, clients with better outcomes made more positive evaluations of themselves and therapy, noticed more positive changes and made more contributions to structuring interactions at initial sessions. Specific early interaction types predict session-by-session outcomes and precede sudden gains in rCBT for SHA.

Cannabis Inflorescence for Medical Purposes: USP Considerations for Quality Attributes.

There is an active and growing interest in cannabis female inflorescence (Cannabis sativa) for medical purposes. Therefore, a definition of its quality attributes can help mitigate public health risks associated with contaminated, substandard, or adulterated products and support sound and reproducible basic and clinical research. As cannabis is a heterogeneous matrix that can contain a complex secondary metabolome with an uneven distribution of constituents, ensuring its quality requires appropriate sampling procedures and a suite of tests, analytical procedures, and acceptance criteria to define the identity, content of constituents (e.g., cannabinoids), and limits on contaminants. As an independent science-based public health organization, United States Pharmacopeia (USP) has formed a Cannabis Expert Panel, which has evaluated specifications necessary to define key cannabis quality attributes. The consensus within the expert panel was that these specifications should differentiate between cannabis chemotypes. Based on the secondary metabolite profiles, the expert panel has suggested adoption of three broad categories of cannabis. These three main chemotypes have been identified as useful for labeling based on the following cannabinoid constituents: (1) tetrahydrocannabinol (THC)-dominant chemotype; (2) intermediate chemotype with both THC and cannabidiol (CBD); and (3) CBD-dominant chemotype. Cannabis plants in each of these chemotypes may be further subcategorized based on the content of other cannabinoids and/or mono- and sesquiterpene profiles. Morphological and chromatographic tests are presented for the identification and quantitative determination of critical constituents. Limits for contaminants including pesticide residues, microbial levels, mycotoxins, and elemental contaminants are presented based on toxicological considerations and aligned with the existing USP procedures for general tests and assays. The principles outlined in this review should be able to be used as the basis of public quality specifications for cannabis inflorescence, which are needed for public health protection and to facilitate scientific research on cannabis safety and therapeutic potential.

Demographic and clinical profile of cardioembolic stroke patients in Western Sydney.

BACKGROUND: Cardioembolism (CE) contributes to a large proportion of ischaemic stroke. AIMS: To evaluate the demographic and clinical profile of CE stroke in Western Sydney. METHODS: A retrospective analysis of ischaemic stroke patients presenting to Westmead Hospital (January-October 2016) was performed. Strokes were classified by TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria into different categories. Clinical and demographic data were collected on all stroke patients, and differences between CE and other stroke causes were identified. RESULTS: Two hundred and twenty-eight consecutive patients (70.9 years; 53% male) were identified. By TOAST criteria, 21 (9%) had large-artery atherosclerosis, 94 (41%) CE, 10 (5%) small-vessel disease, 2 (1%) other aetiology and 101 (44%) undetermined aetiology. A significant proportion of CE stroke patients had cardiovascular risk factors including hypertension (66%), hypercholesterolaemia (50%), diabetes (26%) and ischaemic heart disease (28%). The majority (81%) of patients with CE had atrial flutter/flutter. CE stroke, compared with other types of stroke, was more common in females (56 vs 41%, P = 0.022) and patients with CE stroke were more likely to have previous cerebral ischaemia (34 vs 21%, P = 0.026), suggesting increased recurrence in this group. Of the patients with atrial flutter/flutter (n = 56), the majority (87%) had a high CHA2 DS2 -VASC score (≥2); however, a significant proportion (55.4%) were not on anticoagulation. CONCLUSIONS: Cardioembolic stroke remains a significant burden in Western Sydney, and it is likely that a significant proportion may be preventable, as evidenced by the substantial presence of modifiable cardiovascular risk factors, and inadequate anticoagulation of patients with atrial arrhythmias.

Patient activation in psychotherapy interactions: Developing and validating the consultation interactions coding scheme.

OBJECTIVE: We describe the development of an instrument aiming to offer interaction-level feedback based on "patient activation": client confidence and perceived ability to manage their health. METHOD: Twenty-two session-transcripts from cognitive behavioral therapy with high-users of healthcare were analyzed thematically, producing themes describing in-session interactions. Themes were subcategorized using patient activation theory into high and low activation presentations. Two coders new to the process were trained to use this consultation interactions coding scheme (CICS). Inter-rater reliability (IRR), convergent validity, and clinical utility were assessed and illustrated with extreme cases. RESULTS: Good-to-excellent IRR was achieved. The CICS, therapeutic alliance, and therapist competence were correlated. Client engagement in session-structuring interactions correlated with outcome. The highest CICS scorer showed multiple outcome-improvements, the lowest scorer reported deteriorations. CONCLUSIONS: This study presents the CICS's psychometric properties and indicates the value of client engagement in session-structuring.

Clinical and economic outcomes of remotely delivered cognitive behaviour therapy versus treatment as usual for repeat unscheduled care users with severe health anxiety: a multicentre randomised controlled trial.

BACKGROUND: It is challenging to engage repeat users of unscheduled healthcare with severe health anxiety in psychological help and high service costs are incurred. We investigated whether clinical and economic outcomes were improved by offering remote cognitive behaviour therapy (RCBT) using videoconferencing or telephone compared to treatment as usual (TAU). METHODS: A single-blind, parallel group, multicentre randomised controlled trial was undertaken in primary and general hospital care. Participants were aged ≥18 years with ≥2 unscheduled healthcare contacts within 12 months and scored >18 on the Health Anxiety Inventory. Randomisation to RCBT or TAU was stratified by site, with allocation conveyed to a trial administrator, research assessors masked to outcome. Data were collected at baseline, 3, 6, 9 and 12 months. The primary outcome was change in HAI score from baseline to six months on an intention-to-treat basis. Secondary outcomes were generalised anxiety, depression, physical symptoms, function and overall health. Health economics analysis was conducted from a health service and societal perspective. RESULTS: Of the 524 patients who were referred and assessed for trial eligibility, 470 were eligible and 156 (33%) were recruited; 78 were randomised to TAU and 78 to RCBT. Compared to TAU, RCBT significantly reduced health anxiety at six months, maintained to 9 and 12 months (mean change difference HAI -2.81; 95% CI -5.11 to -0.50; P = 0.017). Generalised anxiety, depression and overall health was significantly improved at 12 months, but there was no significant change in physical symptoms or function. RCBT was strictly dominant with a net monetary benefit of £3,164 per participant at a willingness to pay threshold of £30,000. No treatment-related adverse events were reported in either group. CONCLUSIONS: RCBT may reduce health anxiety, general anxiety and depression and improve overall health, with considerable reductions in health and informal care costs in repeat users of unscheduled care with severe health anxiety who have previously been difficult to engage in psychological treatment. RCBT may be an easy-to-implement intervention to improve clinical outcome and save costs in one group of repeat users of unscheduled care. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov on 19 Nov 2014 with reference number NCT02298036.

Microbiota and Body Composition During the Period of Complementary Feeding.

OBJECTIVES: This study aimed to explore the associations between food group intake, faecal microbiota profile, and body composition during the period of complementary feeding. METHODS: Diet was assessed using a quantitative food frequency questionnaire, faecal microbiota profile was assessed using 16S rRNA gene sequencing, and body composition was assessed using bioelectrical impedance analysis and dual energy x-ray absorptiometry, in a cohort of 50 infants aged 6 to 24 months of age. RESULTS: During this critical period of microbiota development, age was the strongest predictor of microbiota composition with network analysis revealing a cluster of genera positively associated with age. A separate cluster comprised genera associated with fat mass index with Bifidobacterium showing the strongest correlation with fat mass index (rho = 0.55, P = 0.001, false discovery rate [FDR] = 0.018). Dairy intake was both negatively correlated with Bacteroides (rho = -0.49, P < 0.001, FDR = 0.024) and positively correlated with lean mass index (rho = 0.44, P = 0.007, FDR = 0.024). Antibiotics use in the first month of life had the most striking influence on body composition and was associated with an increase in mean body mass index z score of 1.17 (P = 0.001) and body fat of 3.5% (P = 0.001). CONCLUSIONS: Our results suggested that antibiotics use in the first month of life had the most striking influence on body composition in this cohort of infants aged 6 to 24 months, whereas dairy intake interacted with both microbiota and body composition in early life.

The Terroir of Cannabis: Terpene Metabolomics as a Tool to Understand Cannabis sativa Selections.

The phytochemical diversity of Cannabis chemovars is not well understood, and many chemovars were created in informal breeding programs without records of parentage or the criteria for selection. Key criteria for selection sometimes included aroma notes and visual cues, which some breeders associated with pharmacological activity. We hypothesized that the process of selection for scents believed to be related to specific tetrahydrocannabinol levels has resulted in modified terpene biosynthesis in these chemovars. Thirty-two cannabinoids, 29 monoterpenes and 38 sesquiterpenes were measured in 33 chemovars from 5 licensed producers. A classification system based on cannabinoid content was used with targeted metabolomic tools to determine relationships in the phytochemistry. Three monoterpenes, limonene, ß-myrcene, and α-pinene, and two sesquiterpenes, caryophyllene and humulene, were abundant in the majority of chemovars. Nine terpenes were present in tetrahydrocannabinol-dominant chemovars. Three monoterpenes and four sesquiterpenes were predominantly found in cannabidiol-containing chemovars. Low abundance terpenes may have been the aromatic cues identified by breeders. The medicinal activity of some of the terpenes is likely to contribute to the pharmacological effect of specific chemovars. Together, these data demonstrate the synergy of compounds in Cannabis chemovars and point to the need for additional research to understand the phytochemical complexity.

Hope and Schizophrenia in the Latino Family Context.

This study explored hope among Latinos with schizophrenia and their family caregivers to gain a greater understanding of how it is experienced in the family context. Data were collected from 34 participants (14 individuals with schizophrenia; 20 family caregivers). Semistructured in-depth interviews were analyzed using thematic analysis, comparing codes across and within consumer and family caregiver transcripts. Findings revealed that hope was conceptualized as a multidimensional construct and was a vital resource for participants. Specifically, there was an emphasis on contextual factors that included religion and spirituality and interpersonal relationships. Findings underscore the need to expand our understanding of how hope is perceived and developed among Latinos and other underserved groups. This could lead to better recognition of this salient resource to incorporate its varied dimensions into treatment models that address the needs of consumers and family caregivers.

A Sociodemographic Profile of Asian Americans Served in Community Mental Health Centers for a Diagnosis of Schizophrenia Spectrum Disorder.

Little is known about Asian Americans treated for serious psychiatric disorders in the public mental health system. We characterized 75 Asian Americans seen at community mental health centers for a diagnosis of schizophrenia spectrum disorder to anticipate likely clients and gain insights into their service needs. Participants completed in-person interviews and self-report questionnaires on their demographic and social characteristics. The ethnically diverse sample featured mostly foreign-born individuals with long-standing schizophrenia. Findings highlighted participants' differential experience of social adversities and stressful events, but also revealed salient cultural resources that shielded some from the social sequelae of schizophrenia. Recovery-oriented mental health programs staffed by culturally and linguistically compatible providers remain key to engaging this marginalized population in service. Findings also uphold a holistic management of schizophrenia spectrum disorder among racial and ethnic minorities, taking into account the complex social needs of afflicted individuals.

Male-specific Association Between Fat-Free Mass Index and Fecal Microbiota in 2- to 3-Year-Old Australian Children.

OBJECTIVES: Maturation of the gut microbiota has been shown to influence childhood growth, whereas alterations in microbiota composition are proposed to be causally related to the development of overweight and obesity. The objective of this study is to explore the association between microbiota profile, body size, and body composition in young children. METHODS: Fecal microbiota was examined by 16S rRNA gene sequencing, whereas body composition was assessed using the deuterium oxide dilution technique in a cohort of 37 well-nourished 2- to 3-year-old Australian children. RESULTS: Microbiota composition (weighted UniFrac distance) was shown to be significantly associated with FFMI (fat-free mass index) z score (P = 0.027, adonis) in boys but not girls. In boys, FFMI z score was significantly correlated with the relative abundance of an OUT (Operational Taxonomic Unit) belonging to the Ruminococcaceae family (Rho = 0.822, P < 0.001, pFDR (false discovery rate adjusted P value) = 0.002, n = 18). At a FDR <0.2, FFMI z score in boys was positively associated with the relative abundance of OTU related to Dorea formicigenerans and Faecalibacterium prausnitzii and negatively correlated to an OTU related to Bacteroides cellulosilyticus. CONCLUSIONS: These results suggest that previously reported associations between microbiota composition and body size may be driven by an association with fat-free mass, particularly in males.

Single-Lab Validation for Determination of Kavalactones and Flavokavains in Piper methysticum (Kava).

Piper methysticum (Kava) is a plant whose roots are used in the preparation of traditional beverages with spiritual, medicinal, and social importance for the Pacific Islanders. Kava is also sold as a herbal supplement or recreational beverage consumed for its mild inebriating effect in Europe and North America. With an ongoing interest in the safety and quality of kava products, it is necessary to develop a validated method for determination of kava chemical composition to ensure confidence in quality assessment. Thus, an high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method was developed, optimized, and validated for determining six major kavalactones and three flavokavains in kava raw materials and finished products based on AOAC single-laboratory validation guidelines. This is the first fully validated analytical method for measuring kavalactones and flavokavains in a single run. The separation of the analytes was achieved in 10 min with an Agilent Poroshell C18 column using gradient separation. The sample was extracted with methanol first and then acetone. The signals were detected at 240 nm and 355 nm. The limit of quantification was under 1.2 µg/mL (0.3 mg/g) for kavalactones and under 0.35 µg/mL (0.01 mg/g) for flavokavains. The Horwitz ratio values described ranged from 0.3 to 1.82. The spike recovery experiments showed an accuracy between 92 and 105% for all analytes. The results of the study demonstrate that the method is fit for the purpose of determining methysticin, dihydromethysticin, kavain, dihydrokavain, yangonin, desmethoxyyangonin, flavokavain A, flavokavain B, and flavokavain C in kava raw material and finished products (dry-filled capsule, liquid phytocaps, and tincture).