Effectiveness of a mindfulness and acceptance-based intervention for improving the mental health of adolescents with HIV in Uganda: An open-label trial.

Adolescents with HIV (AWH) face the double burden of dealing with challenges presented by their developmental phase while coping with stigma related to HIV, affecting their mental health. Poor mental health complicates adherence to daily treatment regimens, requiring innovative psychosocial support strategies for use with adolescents. We assessed the effectiveness of a mindfulness and acceptance-based intervention on the mental health of AWH in Uganda. One hundred and twenty-two AWH, mean age 17 ±1.59 (range 15 to 19 years), 57% female, receiving care at a public health facility in Kampala were enrolled in an open-label randomized trial (ClinicalTrials.gov: NCT05010317) with assessments at pre-and post-intervention. The mindfulness and acceptance-based intervention involved weekly 90-minute group sessions for four consecutive weeks facilitated by two experienced trainers. Sessions involved clarifying values, skillfully relating to thoughts, allowing and becoming aware of experiences non-judgmentally, and exploring life through trial and error. The control group received the current standard of care. Three mental health domains (depression, anxiety, and internalized stigma) were compared between the intervention and control groups. A linear mixed effects regression was used to analyze the effect of the intervention across the two time points. Results showed that the intervention was associated with a statistically significant reduction in symptoms of depression (ß = -10.72, 95%CI: 6.25, -15.20; p < .0001), anxiety (ß = -7.55, 95%CI: 2.66, -12.43; p = .0003) and stigma (ß = -1.40, 95%CI: 0.66 to -2.15; p = .0004) over time. Results suggest that mindfulness and acceptance-based interventions have the potential to improve the mental health of AWH.

Prediction of MET Overexpression in Lung Adenocarcinoma from Hematoxylin and Eosin Images.

Mesenchymal epithelial transition (MET) protein overexpression is a targetable event in non-small cell lung cancer and is the subject of active drug development. Challenges in identifying patients for these therapies include lack of access to validated testing, such as standardized immunohistochemistry assessment, and consumption of valuable tissue for a single gene/protein assay. Development of prescreening algorithms using routinely available digitized hematoxylin and eosin (H&E)-stained slides to predict MET overexpression could promote testing for those who will benefit most. Recent literature reports a positive correlation between MET protein overexpression and RNA expression. In this work, a large database of matched H&E slides and RNA expression data were leveraged to train a weakly supervised model to predict MET RNA overexpression directly from H&E images. This model was evaluated on an independent holdout test set of 300 overexpressed and 289 normal patients, demonstrating a receiver operating characteristic area under curve of 0.70 (95th percentile interval: 0.66 to 0.74) with stable performance characteristics across different patient clinical variables and robust to synthetic noise on the test set. These results suggest that H&E-based predictive models could be useful to prioritize patients for confirmatory testing of MET protein or MET gene expression status.

Applying an osteopathic intervention to improve mild to moderate mental health symptoms: a mixed-methods feasibility study protocol.

INTRODUCTION: Mental health services are stretched in the UK and are in need of support. One approach that could improve mental health symptoms is osteopathy. Research suggests that osteopathy influences psychophysiological factors, which could lead to improvements in mental health. The first objective of this protocol is to investigate the feasibility and acceptability of four osteopathic interventions. A secondary aim is to evaluate the interventions' effectiveness for improving psychophysiological and mental health outcomes. METHODS AND ANALYSIS: This study will be an explanatory mixed-methods design. Participants will be 30 adults who have mild to moderate mental health symptoms and not experiencing any issues with pain. The feasibility and acceptability of the interventions will be the primary outcomes. Secondary outcomes will be physiological measures including heart rate variability, interoceptive accuracy and blood pressure. Psychological outcomes, collected preintervention and postintervention, will also be measured by five standardised questionnaires, which include: (1) the Depression, Anxiety and Stress Scale (DASS); (2) the International Positive and Negative Affect Schedule-Short-Form; (3) Acceptance and Action Questionnaire-II; (4) the Self as Context Scale and (5) and the Multidimensional Assessment of Interoceptive Awareness Version 2. Participants will be randomised to one of four intervention groups and receive a single intervention treatment session. These intervention groups are: (1) high-velocity and articulation techniques, (2) soft-tissue massage, (3) craniosacral techniques, and (4) a combination of these three approaches. Mixed design two (preintervention and postintervention) by the four interventions analysis of covariance models will be used to analyse the quantitative data for each quantitative measure. Participants will also be interviewed about their experiences of the study and interventions and a thematic analysis will be used to analyse this qualitative data. This will aid the assessment of the feasibility and acceptability of the study design. ETHICS AND DISSEMINATION: The protocol for this feasibility study has received ethical approval from the Department of Psychology Ethics Committee at Swansea University, ethical review reference number: 2022-5603-4810. Feasibility results from this protocol will be published in a peer review journal and presented at both national and international conferences. DISCUSSION: This study will assess the feasibility and acceptability of conducting osteopathic interventions for improving mental health outcomes. The results from this will help to inform the development of a future randomised controlled trial. The study will also produce original data which could provide preliminary evidence of whether osteopathic approaches are of benefit to individual's mental health in the form of effect sizes, even if they are pain-free. TRIAL REGISTRATION NUMBER: NCT05674071.

Idiopathic distal sensory polyneuropathy: ACTTION diagnostic criteria.

OBJECTIVE: To present standardized diagnostic criteria for idiopathic distal sensory polyneuropathy (iDSP) and its subtypes: idiopathic mixed fiber sensory neuropathy (iMFN), idiopathic small fiber sensory neuropathy (iSFN), and idiopathic large fiber sensory neuropathy (iLFN) for use in research. METHODS: The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities and Networks (ACTTION) public-private partnership with the Food and Drug Administration convened a meeting to develop consensus diagnostic criteria for iMFN, iSFN, and iLFN. After background presentations, a collaborative, iterative approach was used to develop expert consensus for new criteria. RESULTS: An iDSP diagnosis requires at least 1 small fiber (SF) or large fiber (LF) symptom, at least 1 SF or LF sign, abnormalities in sensory nerve conduction studies (NCS) or distal intraepidermal nerve fiber density (IENFD), and exclusion of known etiologies. An iMFN diagnosis requires that at least 1 of the above clinical features is SF and 1 clinical feature is LF with abnormalities in sensory NCS or IENFD. Diagnostic criteria for iSFN require at least 1 SF symptom and at least 1 SF sign with abnormal IENFD, normal sensory NCS, and the absence of LF symptoms and signs. Diagnostic criteria for iLFN require at least 1 LF symptom and at least 1 LF sign with normal IENFD, abnormal sensory NCS, and absence of SF symptoms and signs. CONCLUSION: Adoption of these standardized diagnostic criteria will advance research and clinical trials and spur development of novel therapies for iDSPs.

Role of Sulfonylurea Receptor 1 and Glibenclamide in Traumatic Brain Injury: A Review of the Evidence.

Cerebral edema and contusion expansion are major determinants of morbidity and mortality after TBI. Current treatment options are reactive, suboptimal and associated with significant side effects. First discovered in models of focal cerebral ischemia, there is increasing evidence that the sulfonylurea receptor 1 (SUR1)-Transient receptor potential melastatin 4 (TRPM4) channel plays a key role in these critical secondary injury processes after TBI. Targeted SUR1-TRPM4 channel inhibition with glibenclamide has been shown to reduce edema and progression of hemorrhage, particularly in preclinical models of contusional TBI. Results from small clinical trials evaluating glibenclamide in TBI have been encouraging. A Phase-2 study evaluating the safety and efficacy of intravenous glibenclamide (BIIB093) in brain contusion is actively enrolling subjects. In this comprehensive narrative review, we summarize the molecular basis of SUR1-TRPM4 related pathology and discuss TBI-specific expression patterns, biomarker potential, genetic variation, preclinical experiments, and clinical studies evaluating the utility of treatment with glibenclamide in this disease.

MicroRNA Changes in Preconditioning-Induced Neuroprotection.

Preconditioning is a paradigm in which sublethal stress-prior to a more injurious insult-induces protection against injury. In the central nervous system (CNS), preconditioning against ischemic stroke is induced by short durations of ischemia, brief seizures, exposure to anesthetics, and other stresses. Increasing evidence supports the contribution of microRNAs (miRNAs) to the pathogenesis of cerebral ischemia and ischemic tolerance induced by preconditioning. Studies investigating miRNA changes induced by preconditioning have to date identified 562 miRNAs that change expression levels after preconditioning, and 15% of these changes were reproduced in at least one additional study. Of miRNAs assessed as changed by preconditioning in more than one study, about 40% changed in the same direction in more than one study. Most of the studies to assess the role of specific miRNAs in the neuroprotective mechanism of preconditioning were performed in vitro, with fewer studies manipulating individual miRNAs in vivo. Thus, while many miRNAs change in response to preconditioning stimuli, the mechanisms underlying their effects are not well understood. The data does suggest that miRNAs may play significant roles in preconditioning-induced neuroprotection. This review focuses on the current state of knowledge of the possible role of miRNAs in preconditioning-induced cerebral protection.

Anesthetic Management of Mitochondrial Encephalopathy With Lactic Acidosis and Stroke-Like Episodes (MELAS Syndrome) in a High-Risk Pregnancy: A Case Report.

MELAS syndrome (mitochondrial encephalopathy, lactic acidosis, and stroke-like symptoms) is a rare and complex mitochondrial disorder. We present the in-hospital course of a 36-year-old gravida 2, para 0 with MELAS syndrome and severe preeclampsia, complicated by hyponatremia, hyperkalemia, and diabetes. A retained placenta with postpartum hemorrhage required urgent instrumental delivery under spinal anesthesia, transfusion, and intensive care unit admission for pulmonary edema, effusions, and atelectasis. Postpartum endometritis and sepsis also were encountered. This is to our knowledge the first case report of obstetric complications in MELAS syndrome and highlights the salient metabolic sequelae of this syndrome.

In Vogue: Ketamine for Neuroprotection in Acute Neurologic Injury.

Neurologic deterioration following acute injury to the central nervous system may be amenable to pharmacologic intervention, although, to date, no such therapy exists. Ketamine is an anesthetic and analgesic emerging as a novel therapy for a number of clinical entities in recent years, including refractory pain, depression, and drug-induced hyperalgesia due to newly discovered mechanisms of action and new application of its known pharmacodynamics. In this focused review, the evidence for ketamine as a neuroprotective agent in stroke, neurotrauma, subarachnoid hemorrhage, and status epilepticus is highlighted, with a focus on its applications for excitotoxicity, neuroinflammation, and neuronal hyperexcitability. Preclinical modeling and clinical applications are discussed.

Biomarkers of Glycocalyx Injury are Associated with Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage: A Case Series Supporting a New Hypothesis.

BACKGROUND: Delayed cerebral ischemia (DCI) contributes to morbidity following aneurysmal subarachnoid hemorrhage; however, its etiology remains poorly understood. DCI is not only a consequence of angiographic vasospasm, but also involves microthrombosis and neuroinflammation, two events with unexplained phenomenology. The vascular endothelial glycocalyx mediates platelet aggregation and endothelial cell-leukocyte interactions and may play an important role in DCI pathogenesis. METHODS: We present a case series in which we conducted multiplex and singlet enzyme-linked immunosorbent assays of endothelial, glycocalyx, inflammatory, and neuroinjury proteins in both CSF and plasma in three patients during active DCI following SAH. Samples were obtained at baseline following surgical repair of SAH, and again at DCI onset. CSF was sampled at the same time points from in situ external ventricular drains. RESULTS: DCI was associated with significant elevations of soluble markers of endotheliopathy, including vascular adhesion protein-1, soluble fractions of endothelial cell adhesion molecules (CAMs), procoagulant tissue factor, and specific markers of glycocalyx injury, including syndecan-1, and CD44. These phenomena were also associated with an elevation of both circulating and CSF matrix metalloproteinases, which are known to cleave components of the glycocalyx. Elevation of vascular CAM-1 in the CSF with DCI indicated these events were possibly associated with the breakdown of brain microvasculature integrity. CONCLUSIONS: These preliminary data support the hypothesis that glycocalyx injury occurs in SAH, and might contribute to DCI by regulating cerebral microthrombosis and delayed neuroinflammation.

Individual variation evades the prisoner's dilemma.

BACKGROUND: The Prisoner's Dilemma (PD) is a widely used paradigm to study cooperation in evolutionary biology, as well as in fields as diverse as moral philosophy, sociology, economics and politics. Players are typically assumed to have fixed payoffs for adopting certain strategies, which depend only on the strategy played by the opponent. However, fixed payoffs are not realistic in nature. Utility functions and the associated payoffs from pursuing certain strategies vary among members of a population with numerous factors. In biology such factors include size, age, social status and expected life span; in economics they include socio-economic status, personal preference and past experience; and in politics they include ideology, political interests and public support. Thus, no outcome is identical for any two different players. RESULTS: We show that relaxing the assumption of fixed payoffs leads to frequent violations of the payoff structure required for a Prisoner's Dilemma. With variance twice the payoff interval in a linear PD matrix, for example, only 16% of matrices are valid. CONCLUSIONS: A single player lacking a valid PD matrix destroys the conditions for a Prisoner's Dilemma, so between any two players, PD games themselves are fewer still (3% in this case). This may explain why the Prisoner's Dilemma has hardly been found in nature, despite the fact that it has served as a ubiquitous (and still instructive) model in studies of the evolution of cooperation.