9-HODE and 9-HOTrE alter mitochondrial metabolism, increase triglycerides, and perturb fatty acid uptake and synthesis associated gene expression in HepG2 cells.

Non-Alcoholic Fatty Liver Disease (NAFLD) prevalence is rising and can lead to detrimental health outcomes such as Non-Alcoholic Steatohepatitis (NASH), cirrhosis, and cancer. Recent studies have indicated that Cytochrome P450 2B6 (CYP2B6) is an anti-obesity CYP in humans and mice. Cyp2b-null mice are diet-induced obese, and human CYP2B6-transgenic (hCYP2B6-Tg) mice reverse the obesity or diabetes progression, but with increased liver triglyceride accumulation in association with an increase of several oxylipins. Notably, 9-hydroxyoctadecadienoic acid (9-HODE) produced from linoleic acid (LA, 18:2, ω-6) is the most prominent of these and 9-hydroxyoctadecatrienoic acid (9-HOTrE) from alpha-linolenic acid (ALA, 18:3, ω-3) is the most preferentially produced when controlling for substrate concentrations in vitro. Transactivation assays indicate that 9-HODE and 9-HOTrE activate PPARα and PPARγ. In Seahorse assays performed in HepG2 cells, 9-HOTrE increased spare respiratory capacity, slightly decreased palmitate metabolism, and increased non-glycolytic acidification in a manner consistent with slightly increased glutamine utilization; however, 9-HODE exhibited no effect on metabolism. Both compounds increased triglyceride and pyruvate concentrations, most strongly by 9-HOTrE, consistent with increased spare respiratory capacity. qPCR analysis revealed several perturbations in fatty acid uptake and metabolism gene expression. 9-HODE increased expression of CD36, FASN, PPARγ, and FoxA2 that are involved in lipid uptake and production. 9-HOTrE decreased ANGPTL4 expression and increased FASN expression consistent with increased fatty acid uptake, fatty acid production, and AMPK activation. Our findings support the hypothesis that 9-HODE and 9-HOTrE promote steatosis, but through different mechanisms as 9-HODE is directly involved in fatty acid uptake and synthesis; 9-HOTrE weakly inhibits mitochondrial fatty acid metabolism while increasing glutamine use.

Change in suicidal ideation, depression, and anxiety following collaborative care in the community.

BACKGROUND: The Collaborative Care Model (CoCM) increases access to mental health treatment and improves outcomes among patients with mild to moderate psychopathology; however, it is unclear how effective CoCM is for patients with elevated suicide risk. METHODS: We examined data from the Penn Integrated Care program, a CoCM program including an intake and referral management center plus traditional CoCM services implemented in primary care clinics within a large, diverse academic medical system. In this community setting, we examined: (1) characteristics of patients with and without suicidal ideation who initiated CoCM, (2) changes in suicidal ideation (Patient Health Questionnaire-9 [PHQ-9] item 9), depression (PHQ-9 total scores), and anxiety (Generalized Anxiety Disorder Scale-7 scores) from the first to last CoCM visit overall and across demographic subgroups, and (3) the relationship between amount of CoCM services provided and degree of symptom reduction. RESULTS: From 2018 to 2022, 3,487 patients were referred to CoCM, initiated treatment for at least 15 days, and had completed symptom measures at the first and last visit. Patients were 74% female, 45% Black/African American, and 45% White. The percentage of patients reporting suicidal ideation declined 11%-7% from the first to last visit. Suicidal ideation severity typically improved, and very rarely worsened, during CoCM. Depression and anxiety declined significantly among patients with and without suicidal ideation and across demographic subgroups; however, the magnitude of these declines differed across race, ethnicity, and age. Patients with suicidal ideation at the start of CoCM had higher depression scores than patients without suicidal ideation at the start and end of treatment. Longer CoCM episodes were associated with greater reductions in depression severity. CONCLUSIONS: Suicidal ideation, depression, and anxiety declined following CoCM among individuals with suicidal ideation in a community setting. Findings are consistent with emerging evidence from clinical trials suggesting CoCM's potential for increasing access to mental healthcare and improving outcomes among patients at risk for suicide.

Treating individuals with suicidal ideation in primary care: Patient-level characteristics associated with follow-up in the Collaborative Care Model.

INTRODUCTION: The Collaborative Care Model (CoCM) is an evidence-based approach which embeds behavioral health providers (BHPs) into primary care. Whether patients with suicidal ideation (SI) are willing to engage in CoCM is unclear. METHODS: Using Patient Health Questionnaire-9 (PHQ-9) administrative data from primary care practices within an urban academic health system, we identified patients with and without SI who were referred to a CoCM BHP. We compared engagement, defined as attendance at ≥1 CoCM visit, across groups. RESULTS: Between 2018 and 2022, 7391 primary care patients were referred to a CoCM BHP. Eight hundred and ninety-two of these patients reported SI on the PHQ-9 (754 on "several days" during the previous 2 weeks and 138 on "more than half or most days"). Across groups, most patients engaged in CoCM. Patients reporting SI on several days engaged at a lower rate (61.4%) than those reporting SI on more than half or most days (65.9%). Both SI groups engaged at a lower rate than the 6499 patients who did not report SI (67.5%). CONCLUSION: Most patients referred to a CoCM BHP engaged in ≥1 visit. Rates were lower for patients with SI, with the lowest rate among those reporting SI on several days.

Use of Glucocorticoids in Patients With Cancer: Potential Benefits, Harms, and Practical Considerations for Clinical Practice.

PURPOSE: Glucocorticoids are commonly used in patients with cancer for symptom relief or as part of their anticancer treatment. Despite their frequent use, indications and dosing regimens are not exclusively evidence-based and can come with a multitude of adverse effects, some of which can be life-threatening. The objective of this review is to update our current state of knowledge on the use of glucocorticoids in adult patients with cancer. METHODS AND MATERIALS: A comprehensive literature review (1949-2022) was conducted using search terms "glucocorticoids," "corticosteroids," and "cancer." Information was organized by main concepts including indications, potential benefits, and prevention and management of common side effects of glucocorticoid therapy, in addition to appropriate dosing and taper regimens. RESULTS: Glucocorticoids can be highly effective in improving outcomes and quality of life in patients with cancer. Their uses include management of disease manifestations, symptoms, and complications of cancer treatment. The lowest effective dose should be used and treatment duration should be minimized as clinically feasible. Side effects can be minimized by careful monitoring, continued assessment of benefits versus harms, and preventative measures for expected side effects. CONCLUSIONS: This review provides general principles and practical recommendations on the use of glucocorticoids in patients with cancer. Further prospective studies on the outcomes of patients on glucocorticoids may help guide practice.

The first UK report of a rare Cryptosporidium hominis genetic variant isolated during a complex Scottish swimming pool outbreak.

Cryptosporidium species are responsible for causing the majority of parasite-related gastrointestinal infections in the UK. This report describes an outbreak of 12 laboratory-confirmed cryptosporidiosis cases identified as part of a Scottish swimming pool investigation, with 9 primary and 3 secondary cases occurring over an 8-week period. Molecular speciation was successful for 11/12 cases, which revealed 10 Cryptosporidium hominis cases and 1 Cryptosporidium parvum case. Of the 10 C. hominis cases, further typing identified 7 as being an unusual sub-type, IbA6G3, which is the first description in the UK of this rare variant. The remaining three C. hominis cases were identified as the common IbA10G2 subtype. Following implementation of control measures on two occasions, no further cases were reported. This report highlights the importance of molecular typing to identify and characterize outbreaks, and emphasizes the need to adhere to swimming pool guidance. It also raises awareness of the potential for outbreaks to involve multiple species/sub-types, and emphasizes the importance of strong public health leadership to ensure effective multi-agency investigations and management of outbreaks.

Risk factors for carbapenemase-producing organisms among inpatients in Scotland: A national matched case-control study.

OBJECTIVE: To determine risk factors for carbapenemase-producing organisms (CPOs) and to determine the prognostic impact of CPOs. DESIGN: A retrospective matched case-control study. PATIENTS: Inpatients across Scotland in 2010-2016 were included. Patients with a CPO were matched with 2 control groups by hospital, admission date, specimen type, and bacteria. One group comprised patients either infected or colonized with a non-CPO and the other group were general inpatients. METHODS: Conditional logistic regression models were used to identify risk factors for CPO infection and colonization, respectively. Mortality rates and length of postisolation hospitalization were compared between CPO and non-CPO patients. RESULTS: In total, 70 CPO infection cases (with 210 general inpatient controls and 121 non-CPO controls) and 34 CPO colonization cases (with 102 general inpatient controls and 60 non-CPO controls) were identified. Risk factors for CPO infection versus general inpatients were prior hospital stay (adjusted odds ratio [aOR], 4.05; 95% confidence interval [CI], 1.52-10.78; P = .005), longer hospitalization (aOR, 1.07; 95% CI, 1.04-1.10; P < .001), longer intensive care unit (ICU) stay (aOR, 1.41; 95% CI, 1.01-1.98; P = .045), and immunodeficiency (aOR, 3.68; 95% CI, 1.16-11.66; P = .027). Risk factors for CPO colonization were prior high-dependency unit (HDU) stay (aOR, 11.46; 95% CI, 1.27-103.09; P = .030) and endocrine, nutritional, and metabolic (ENM) diseases (aOR, 3.41; 95% CI, 1.02-11.33; P = .046). Risk factors for CPO infection versus non-CPO infection were prolonged hospitalization (aOR, 1.02; 95% CI, 1.00-1.03; P = .038) and HDU stay (aOR, 1.13; 95% CI, 1.02-1.26; P = .024). No differences in mortality rates were detected between CPO and non-CPO patients. CPO infection was associated with longer hospital stay than non-CPO infection (P = .041). CONCLUSIONS: A history of (prolonged) hospitalization, prolonged ICU or HDU stay; ENM diseases; and being immunocompromised increased risk for CPO. CPO infection was not associated with increased mortality but was associated with prolonged hospital stay.

Radiological prevalence of osteoarthritis of the cervical region in 104 performing Warmblood jumpers.

BACKGROUND: Cervical osteoarthritis (OA) has been documented as a potential source of pain and poor performance in sport horses. OBJECTIVES: To assess the prevalence of cervical OA in a population of Warmblood jumpers and its correlation with age, level of performance, neck pain and mobility. STUDY DESIGN: Descriptive observational study. METHODS: Warmblood jumpers free of lameness or neurological disorders were selected. Cervical pain and range of motion of the neck were subjectively assessed. Left to right lateral views were taken at C3-C4, C4-C5, C5-C6 and C6-C7. The presence of OA at the cervical articular process joints (APJs) was evaluated and graded as absent, mild or moderate to severe by three board-certified radiologists. The agreement between radiologists and the potential associations between OA grades with age and other variables were statistically assessed (P < .05). RESULTS: One hundred and four horses were included [median age = 10 years (range 6-18 years)]. Agreement between radiologists varied from fair to substantial (Kappa-weighted 0.37-0.61). The C6-C7 APJ was most commonly affected by OA with only 32.7% of APJ considered free of radiographic abnormalities at this location versus 60.5% at C5-C6, 81.7% at C4-C5 and 84.6% at C3-C4. Horses competing in higher level classes (peak of performance) had significantly higher OA grades at C6-C7 (P = .013). There was no association between age, age when started jumping, neck pain and neck range of motion with the presence of OA on radiographs. MAIN LIMITATIONS: Open enrolment and lack of orthogonal views. CONCLUSIONS: This study showed that, although there is a range of interpretation of radiographic findings of the APJ, OA of the caudal cervical region is not rare in performing sound Warmblood jumpers. This suggests that OA in the caudal cervical region may be of low clinical significance.

Ensuring that COVID-19 research is inclusive: guidance from the NIHR INCLUDE project.

OBJECTIVE: To provide guidance to researchers, funders, regulators and study delivery teams to ensure that research on COVID-19 is inclusive, particularly of groups disproportionately affected by COVID-19 and who may have been historically under-served by research. SUMMARY OF KEY POINTS: Groups who are disproportionately affected by COVID-19 include (but are not limited to) older people, people with multiple long-term conditions, people with disabilities, people from Black, Asian and Ethnic minority groups, people living with obesity, people who are socioeconomically deprived and people living in care homes. All these groups are under-served by clinical research, and there is an urgent need to rectify this if COVID-19 research is to deliver relevant evidence for these groups who are most in need. We provide a framework and checklists for addressing key issues when designing and delivering inclusive COVID-19 research, based on the National Institute for Health Research INnovations in CLinical trial design and delivery for the UnDEr-served project roadmap. Strong community engagement, codevelopment and prioritisation of research questions and interventions are essential. Under-served groups should be represented on funding panels and ethics committees, who should insist on the removal of barriers to participation. Exclusion criteria should be kept to a minimum; intervention delivery and outcome measurement should be simple, flexible and tailored to the needs of different groups, and local advice on the best way to reach and engage with under-served communities should be taken by study delivery teams. Data on characteristics that allow identification of under-served groups must be collected, analyses should include these data to enable subgroup comparisons and results should be shared with under-served groups at an early stage. CONCLUSION: Inclusive COVID-19 research is a necessity, not a luxury, if research is to benefit all the communities it seeks to serve. It requires close engagement with under-served groups and attention to aspects of study topic, design, delivery, analysis and dissemination across the research life cycle.

Developing a roadmap to improve trial delivery for under-served groups: results from a UK multi-stakeholder process.

BACKGROUND: Participants in clinical research studies often do not reflect the populations for which healthcare interventions are needed or will be used. Enhancing representation of under-served groups in clinical research is important to ensure that research findings are widely applicable. We describe a multicomponent workstream project to improve representation of under-served groups in clinical trials. METHODS: The project comprised three main strands: (1) a targeted scoping review of literature to identify previous work characterising under-served groups and barriers to inclusion, (2) surveys of professional stakeholders and participant representative groups involved in research delivery to refine these initial findings and identify examples of innovation and good practice and (3) a series of workshops bringing together key stakeholders from funding, design, delivery and participant groups to reach consensus on definitions, barriers and a strategic roadmap for future work. The work was commissioned by the UK National Institute for Health Research Clinical Research Network. Output from these strands was integrated by a steering committee to generate a series of goals, workstream plans and a strategic roadmap for future development work in this area. RESULTS: 'Under-served groups' was identified and agreed by the stakeholder group as the preferred term. Three-quarters of stakeholders felt that a clear definition of under-served groups did not currently exist; definition was challenging and context-specific, but exemplar groups (e.g. those with language barriers or mental illness) were identified as under-served. Barriers to successful inclusion of under-served groups could be clustered into communication between research teams and participant groups; how trials are designed and delivered, differing agendas of research teams and participant groups; and lack of trust in the research process. Four key goals for future work were identified: building long-term relationships with under-served groups, developing training resources to improve design and delivery of trials for under-served groups, developing infrastructure and systems to support this work and working with funders, regulators and other stakeholders to remove barriers to inclusion. CONCLUSIONS: The work of the INCLUDE group over the next 12 months will build on these findings by generating resources customised for different under-served groups to improve the representativeness of trial populations.

Psychiatric consultation to the postpartum mother.

The immediate postpartum period is a time of acute vulnerability to mental illness, which presents unique challenges for the psychiatric consultant. Because the postpartum hospital stay is typically brief, the consultant must have a working knowledge of postpartum physiology and the myriad forms of mental illness that may emerge in this vulnerable time, in order to quickly make a diagnosis and formulate a treatment plan. This review aims to characterize the most common reasons for postpartum consultation, review postpartum physiology and psychiatric conditions, and propose an evidence-based, practical approach to treatment. A literature search using the terms "postpartum," "obstetric," "consultation," and "psychiatry" yielded six studies that identified reasons for psychiatric consultation to the obstetrics and gynecology services. These studies informed the structure of the article such that we review the most common reasons for consultation and how to approach each issue. The most common reason for consultation is past psychiatric history, often in the absence of current symptoms. For each clinical situation, including depression, adverse birth events, and psychosis, we present a differential diagnosis, as well as risk factors, clinical signs, and recommended treatment.

The prevalence of hepatitis C virus among people of South Asian origin in Glasgow - results from a community based survey and laboratory surveillance.

BACKGROUND: South Asians often present late with HCV or HBV related liver disease which could have been avoided with early diagnosis and subsequent treatment; however the prevalence of HCV/HBV among South Asians in Glasgow is not known. Accordingly, to inform the need for case finding among this group we aimed to examine the prevalence of Hepatitis C virus (HCV) among South Asians living in Glasgow. METHODS: A community-based survey recruited individuals at six mosques and four community centres serving the South Asian community during 2009-2010; participants had predominantly never been HCV tested. Laboratory surveillance data involving all individuals tested for HCV during 1993-2009 were examined and South Asians were identified using Nam Pehchan software. RESULTS: In the community-based survey, 2.6% of 1288 participants tested HCV-antibody positive; the prevalence ranged from 0.6% among those born in the UK to 3.1% among those born in Pakistan. The odds of testing HCV-antibody positive were significantly raised among those who had surgery in South Asia (aOR: 5.0, 95% CI: 2.0-12.3) and had either medical/dental treatment or an injection in South Asia (aOR: 2.2, 95% CI: 1.0-5.0). Of 6404 South Asians identified from laboratory surveillance data, 9.3% tested HCV positive. An estimated 38% (330/870) of HCV-infected South Asians living in Glasgow remain undiagnosed. CONCLUSIONS: South Asians living in Glasgow, particularly those born outside the UK are at greater risk of HCV infection than the general population. Efforts to increase awareness and testing in this population are warranted.

Non-toxigenic Vibrio cholerae bacteraemia: case report and review of the literature.

Vibrio cholerae is a serious public health problem worldwide, but in the UK, V. cholerae infections are rare. Here, we report a case of V. cholerae bacteraemia in an elderly patient. To our knowledge, this is the first non-travel-related V cholerae bacteraemia in the UK.