Transpersonal perspectives of spiritual experiences in epilepsy

Insight into the phenomenology of spiritual experiences of those with epilepsy offers a move away from current reductive explanations. This research will offer a voice for an often ignored and stigmatised group, aiming to understand their attribution of spirituality to experiences of auras. Connections with other altered states of consciousness will explore whether epileptic experiences of spirituality can be placed within a wider context of well-being and the human condition

PD-1, PD-L1 and PD-L2 Gene Expression on T-Cells and Natural Killer Cells Declines in Conjunction with a Reduction in PD-1 Protein during the Intensive Phase of Tuberculosis Treatment.

BACKGROUND: The PD-1 axis is a cell intrinsic immunoregulatory pathway that mediates T cell exhaustion in chronic infection particularly in some viral infections. We hypothesized that PD-1, PD-L1 and PD-L2 would be highly expressed in untreated tuberculosis patients compared to controls due to their chronic infection and would decrease with successful TB treatment. MATERIALS AND METHODS: Untreated tuberculosis patients (n = 26) were recruited at diagnosis and followed up during treatment. Household contacts (n = 24) were recruited to establish baseline differences. Blood gene expression ex vivo was investigated using qRT-PCR. Flow cytometry was performed to establish protein expression patterns. RESULTS: PD-L1 gene expression was found to be elevated in active TB disease; however, this was not observed for PD-1 or PD-L2. The intensive phase of TB treatment was associated with a significant decline in PD-1, PD-L1 and PD-L2 gene expression. PD-1 protein expression on the surface of NK cells, CD8+ and CD4+ T cells was similar in patients with active TB disease compared to controls but declined with successful TB treatment, with the greatest decline occurring on the NK cells followed by CD8+ T cells and then CD4+ T cells. Granzyme B/PD-1 co-expression declined with successful intensive phase treatment. CONCLUSION: Modulation of PD-1/PD-L1 pathway through TB treatment indicates changes in the peripheral T cell response caused by live Mycobacterium tuberculosis (Mtb) followed by the response to dead bacilli, antigen-release and immuno-pathology resolution. The PD-1 axis could be a host drug target for immunomodulatory treatments in the future

Using Environmental DNA to Detect Whales and Dolphins in the New York Bight

Determining how cetaceans and other threatened marine animals use coastal habitats is critical to the effective conservation of these species. Environmental DNA (eDNA) is an emerging tool that can potentially be used to detect cetaceans over broad spatial and temporal scales. In particular, eDNA may present a useful complementary method for monitoring their presence during visual surveys in nearshore areas, and for co-detecting prey. In conjunction with ongoing visual surveys, we tested the ability of eDNA metabarcoding to detect the presence and identity of cetaceans in the New York Bight (NYB), and to identify fish species (potential prey) present in the area. In almost all cases in which humpback whales and dolphins were visually observed, DNA from these species was also detected in water samples. To assess eDNA degradation over time, we took samples in the same location 15 and 30min after a sighting in seven instances, and found that eDNA often, but not always, dropped to low levels after 30min. Atlantic menhaden were detected in all samples and comprised the majority of fish sequences in most samples, in agreement with observations of large aggregations of this important prey species in the NYB. While additional data are needed to better understand how factors such as behavior and oceanographic conditions contribute to the longevity of eDNA signals, these results add to a growing body of work indicating that eDNA is a promising tool to complement visual and acoustic surveys of marine megafauna

A transpersonal exploration of epilepsy & its numinous, cosmic states

Transpersonal experiences offer personal transformation by highlighting the contrast between felt experience and a previously held sense of self-identity and world (Walsh & Vaughn, 1980). They are highly subjective — often labelled as irrational or pathological (Walsh & Vaughan, 1993), thus posing difficulty for ‘objective’ approaches to human research (Anderson & Braud, 2011). A contemporary, qualitative, autobiographical genre of research, auto-ethnography offers voice to personal experience in such a way that the quality and depth of experience is felt by the reader (Boylorn, 2006; Jago, 2002). It seeks to evoke a lived experience within a socio-cultural context, initiating personal and societal change (Ellis, 2000). Using a variety of creative genres (Bochner & Ellis, 2002), it emphasises embodied expression from the heart (Grant, Short & Turner, 2013). In this talk I will explain how auto-ethnography can be applied as a transpersonal research method. I will discuss its use within my research into transpersonal experiences occurring during epileptic events and the specific character and intensity of the feelings that accompany them (Trimble & Freeman, 2006). Examination of altered states of consciousness is an established area in transpersonal psychology (e.g. Tart, 1975; Grof, 1975). In my research, I will be using a lucid dreaming technique developed by Hamilton (2014) to explore my own epileptic events. This is an established therapeutic technique that I employ in my transpersonal practice. I will be using this technique of my own epileptic experiences to present and analyse using the auto-ethnographic method. By providing details into the auto-ethnographic approach, I will demonstrate how it provides a deep understanding of experiences that are not easily accessible through other research methods (Laslett, 1999)

Mobilisation in the EveNing to TreAt deLirium (MENTAL):protocol for a mixed-methods feasibility randomised controlled trial

INTRODUCTION: Delirium is common in critically ill patients and is associated with longer hospital stays, increased mortality and higher healthcare costs. A number of risk factors have been identified for the development of delirium in intensive care, two of which are sleep disturbance and immobilisation. Non-pharmacological interventions for the management of intensive care unit (ICU) delirium have been advocated, including sleep protocols and early mobilisation. However, there is a little published evidence evaluating the feasibility and acceptability of evening mobilisation. METHODS AND ANALYSIS: Mobilisation in the EveNing to TreAt deLirium (MENTAL) is a two-centre, mixed-methods feasibility randomised controlled trial (RCT). Sixty patients will be recruited from ICUs at two acute NHS trusts and randomised on a 1:1 basis to receive additional evening mobilisation, delivered between 19:00 and 21:00, or standard care. The underpinning hypothesis is that the physical exertion associated with evening mobilisation will promote better sleep, subsequently having the potential to reduce delirium incidence. The primary objective is to assess the feasibility and acceptability of a future, multicentre RCT. The primary outcome measures, which will determine feasibility, are recruitment and retention rates, and intervention fidelity. Acceptability of the intervention will be evaluated through semi-structured interviews of participants and staff. Secondary outcome measures include collecting baseline, clinical and outcome data to inform the power calculations of a future definitive trial. ETHICS AND DISSEMINATION: Ethical approval has been obtained through the Wales Research and Ethics Committee 6 (22/WA/0106). Participants are required to provide written informed consent. We aim to disseminate the findings through international conferences, international peer-reviewed journals and social media. TRIAL REGISTRATION NUMBER: NCT05401461

Intrathecal enzyme replacement for Hurler syndrome: biomarker association with neurocognitive outcomes.

PurposeAbnormalities in cerebrospinal fluid (CSF) have been reported in Hurler syndrome, a fatal neurodegenerative lysosomal disorder. While no biomarker has predicted neurocognitive response to treatment, one of these abnormalities, glycosaminoglycan nonreducing ends (NREs), holds promise to monitor therapeutic efficacy. A trial of intrathecal enzyme replacement therapy (ERT) added to standard treatment enabled tracking of CSF abnormalities, including NREs. We evaluated safety, biomarker response, and neurocognitive correlates of change.MethodsIn addition to intravenous ERT and hematopoietic cell transplantation, patients (N = 24) received intrathecal ERT at four peritransplant time points; CSF was evaluated at each point. Neurocognitive functioning was quantified at baseline, 1 year, and 2 years posttransplant. Changes in CSF biomarkers and neurocognitive function were evaluated for an association.ResultsOver treatment, there were significant decreases in CSF opening pressure, biomarkers of disease activity, and markers of inflammation. Percent decrease in NRE from pretreatment to final intrathecal dose posttransplant was positively associated with percent change in neurocognitive score from pretreatment to 2 years posttransplant.ConclusionIntrathecal ERT was safe and, in combination with standard treatment, was associated with reductions in CSF abnormalities. Critically, we report evidence of a link between a biomarker treatment response and neurocognitive outcome in Hurler syndrome

What motivates community mental and behavioral health organizations to participate in LGBTQ+ cultural competency trainings?

LGBTQ+ populations show elevated rates of poor mental health and substance use relative to their heterosexual and cisgender counterparts but often experience stigma and marginalization when seeking mental health care. Mental and behavioral health organizations and therapists recognize a need for LGBTQ+ cultural competency training opportunities and are interested in participating in these trainings. Professional organizations and state licensing bodies should consider policies that require accredited graduate programs and continuing education opportunities to include LGBTQ+ training and competencies.The constantly evolving language, understanding, and cultural context regarding the mental health of lesbian, gay, bisexual, transgender, queer, and other sexual and gender diverse individuals (LGBTQ+) require mental health providers to obtain LGBTQ+ cultural competency training to be affirmative and effective with this population. Unfortunately, many providers are not obtaining this ongoing training and mental health disparities continue to plague LGBTQ+ populations. Guided by the Consolidation Framework for Implementation Research (CFIR), we conducted eight focus groups with community mental and behavioral health organization (MBHO) administrators (e.g., directors, clinical supervisors) and therapists to explore what factors facilitated or inhibited their adoption and implementation of a multicomponent LGBTQ+ cultural competency training program that required administrator and therapist participation in multiple learning sessions over several months (i.e., workshop, clinical consultation, and organizational technical assistance). Results from template analysis supported CFIR-aligned themes, including characteristics of individuals, inner setting, outer setting, and process, and two additional codes—marketing and other/previous training opportunities—emerged from the focus group data. Findings suggest that therapists are motivated to engage in such a program because they want to feel more efficacious, and administrators see the benefits of LGBTQ+ training programs for their clientele and marketing. Barriers to adoption and implementation include cost and personnel resistance, although participants believed these barriers were surmountable. Emphasizing therapist efficacy, clientele need, and benefits for marketing mental and behavioral health services could motivate MBHOs’ and therapists’ adoption and implementation of LGBTQ+ cultural competency training.This work was supported by the University of Maryland Prevention Research Center cooperative agreement no. U48DP006382 from the Centers for Disease Control and Prevention (CDC). Any interpretations and opinions expressed herein are solely those of the authors and may not reflect those of the CDC

Disseminated Effects in Agent Based Models: A Potential Outcomes Framework and Application to Inform Pre-Exposure Prophylaxis Coverage Levels for HIV Prevention

Pre-exposure prophylaxis (PrEP) for HIV prevention may not only benefit the individual who uses it, but also their uninfected sexual risk contacts. We developed an agent-based model using a novel trial emulation approach to quantify disseminated effects of PrEP use among men who have sex with men in Atlanta, USA from 2015 to 2017. Components (subsets of agents connected through partnerships in a sexual network, but not sharing partnerships with any other agents) were first randomized to an intervention coverage level or control, then within intervention components, eligible agents were randomized to PrEP. We estimated direct and disseminated (indirect) effects using randomization-based estimators and reported corresponding 95% simulation intervals across scenarios ranging from 10% to 90% coverage in the intervention components. A population of 11,245 agents was simulated with an average of 1,551 components identified. Comparing agents randomized to PrEP in 70% coverage components to control agents, there was a 15% disseminated risk reduction in HIV incidence (95% simulation intervals = 0.65, 1.05). Individuals not on PrEP may receive a protective benefit by being in a sexual network with higher PrEP coverage. Agent-based models are useful to evaluate possible direct and disseminated effects of HIV prevention modalities in sexual networks

Associations between long chain polyunsaturated fatty acids and cardiovascular lipid risk factors in youth with type 1 diabetes: SEARCH Nutrition Ancillary Study

In this longitudinal study we explored the relationships between plasma n-3 and n-6 polyunsaturated fatty acids (PUFAs) and Δ5 and Δ6 desaturase activities (D5D and D6D, respectively) and fasting lipids in youth with type 1 diabetes (T1D)

The ecology of immune state in a wild mammal, Mus musculus domesticus

The immune state of wild animals is largely unknown. Knowing this and what affects it is important in understanding how infection and disease affects wild animals. The immune state of wild animals is also important in understanding the biology of their pathogens, which is directly relevant to explaining pathogen spillover among species, including to humans. The paucity of knowledge about wild animals' immune state is in stark contrast to our exquisitely detailed understanding of the immunobiology of laboratory animals. Making an immune response is costly, and many factors (such as age, sex, infection status, and body condition) have individually been shown to constrain or promote immune responses. But, whether or not these factors affect immune responses and immune state in wild animals, their relative importance, and how they interact (or do not) are unknown. Here, we have investigated the immune ecology of wild house mice—the same species as the laboratory mouse—as an example of a wild mammal, characterising their adaptive humoral, adaptive cellular, and innate immune state. Firstly, we show how immune variation is structured among mouse populations, finding that there can be extensive immune discordance among neighbouring populations. Secondly, we identify the principal factors that underlie the immunological differences among mice, showing that body condition promotes and age constrains individuals’ immune state, while factors such as microparasite infection and season are comparatively unimportant. By applying a multifactorial analysis to an immune system-wide analysis, our results bring a new and unified understanding of the immunobiology of a wild mammal