Charting the Course: Insights into Neuroendocrine Tumor Dynamics in the United States.

OBJECTIVE: To explore changing trends and characteristics in neuroendocrine tumors (NETs) epidemiology, focusing on demographics, clinical aspects, and survival, including the impact of social determinants of health (SDOH) on outcomes. BACKGROUND: The escalating incidence and prevalence of NETs underscore the pressing need for updated epidemiologic data to reveal the evolving landscape of this condition. Access to current information is imperative for informing clinical strategies and public health initiatives targeting NETs. METHODS: A retrospective, population-based study analyzed NET patient data from 1975 to 2020, using the Surveillance, Epidemiology, and End Results (SEER 8, 12, 18) program. We calculated annual age-adjusted incidence, prevalence, and 5-year overall survival (OS) rates. Survival trends from 2000 to 2019 were examined, employing the Fine-Gray model to evaluate cancer-specific mortality. RESULTS: NETs' age-adjusted incidence rate quadrupled from 1.5 per 100,000 in 1975 to 6.0 per 100,000 in 2020. A decline in incidence occurred from 6.8 per 100,000 in 2019 to 6.0 per 100,000 in 2020. All-cause survival multivariable analysis demonstrated high grade (HR: 2.95, 95% CI: 2.63-3.09, P<0.001), single patients (HR: 1.49, 95% CI: 1.45-1.54, P<0.001), and Black patients (HR: 1.17, 95% CI:1.13-1.22, P<0.001) all had worse survival than their controls. CONCLUSION: In conclusion, our study shows a steady increase in NETs incidence until 2019, with a decline in 2020. Understanding the reasons behind this trend is vital for improved management and public health planning. Further research should focus on the factors driving these changes to enhance our understanding of NET epidemiology.

Differences in Discounting Behavior and Brain Responses for Food and Money Reward.

Most neuroeconomic research seeks to understand how value influences decision-making. The influence of reward type is less well understood. We used functional magnetic resonance imaging (fMRI) to investigate delay discounting of primary (i.e., food) and secondary rewards (i.e., money) in 28 healthy, normal-weighted participants (mean age = 26.77; 18 females). To decipher differences in discounting behavior between reward types, we compared how well-different option-based statistical models (exponential, hyperbolic discounting) and attribute-wise heuristic choice models (intertemporal choice heuristic, dual reasoning and implicit framework theory, trade-off model) captured the reward-specific discounting behavior. Contrary to our hypothesis of different strategies for different rewards, we observed comparable discounting behavior for money and food (i.e., exponential discounting). Higher k values for food discounting suggest that individuals decide more impulsive if confronted with food. The fMRI revealed that money discounting was associated with enhanced activity in the right dorsolateral prefrontal cortex, involved in executive control; the right dorsal striatum, associated with reward processing; and the left hippocampus, involved in memory encoding/retrieval. Food discounting, instead, was associated with higher activity in the left temporoparietal junction suggesting social reinforcement of food decisions. Although our findings do not confirm our hypothesis of different discounting strategies for different reward types, they are in line with the notion that reward types have a significant influence on impulsivity with primary rewards leading to more impulsive choices.

"A perfect storm": Autistic experiences of menopause and midlife.

LAY ABSTRACT: Previous studies report that menopause can be a very difficult transition for some autistic people. This study focuses on how autistic people experience menopause and what support and information might help them. Autistic Community Research Associates played an important role in the research and co-authored this article. We held four focus groups and eight interviews online with 24 autistic participants who lived in either Canada (n = 13) or the United Kingdom (n = 11). We analysed participant conversations using a method called reflexive thematic analysis. Participants described many intense challenges during menopause. Four themes and eight subthemes were identified across participant groups: (1) Complexity, multiplicity and intensity of symptoms (0 subthemes); (2) Life experience and adversity converging at midlife (three subthemes); (3) The importance of knowledge and connection (two subthemes); and (4) Barriers to support and care (three subthemes). The experiences of our participants may not be the same as other autistic people, and the study could have been more inclusive of diverse autistic groups. However, hearing about the experiences of others may provide reassurance to autistic people who struggle with menopause and let them know they are not alone.

Potent HPIV3-neutralizing IGHV5-51 Antibodies Identified from Multiple Individuals Show L Chain and CDRH3 Promiscuity.

Human parainfluenza virus 3 (HPIV3) is a widespread pathogen causing severe and lethal respiratory illness in at-risk populations. Effective countermeasures are in various stages of development; however, licensed therapeutic and prophylactic options are not available. The fusion glycoprotein (HPIV3 F), responsible for facilitating viral entry into host cells, is a major target of neutralizing Abs that inhibit infection. Although several neutralizing Abs against a small number of HPIV3 F epitopes have been identified to date, relatively little is known about the Ab response to HPIV3 compared with other pathogens, such as influenza virus and SARS-CoV-2. In this study, we aimed to characterize a set of HPIV3-specific Abs identified in multiple individuals for genetic signatures, epitope specificity, neutralization potential, and publicness. We identified 12 potently neutralizing Abs targeting three nonoverlapping epitopes on HPIV3 F. Among these, six Abs identified from two different individuals used Ig heavy variable gene IGHV 5-51, with five of the six Abs targeting the same epitope. However, despite the use of the same H chain variable (VH) gene, these Abs used multiple different L chain variable genes (VL) and diverse H chain CDR 3 (CDRH3) sequences. Together, these results provide further information about the genetic and functional characteristics of HPIV3-neutralizing Abs and suggest the existence of a reproducible VH-dependent Ab response associated with VL and CDRH3 promiscuity. Understanding sites of HPIV3 F vulnerability and the genetic and molecular characteristics of Abs targeting these sites will help guide efforts for effective vaccine and therapeutic development.

Modelling Treatment Sequences in Immunology: Optimizing Patient Outcomes.

INTRODUCTION: For some immune-mediated disorders, despite the range of therapies available there is limited evidence on which treatment sequences are best for patients and healthcare systems. We investigated how their selection can impact outcomes in an Italian setting. METHODS: A 3-year state-transition treatment-sequencing model calculated potential effectiveness improvements and budget reallocation considerations associated with implementing optimal sequences in ankylosing spondylitis (AS), Crohn's disease (CD), non-radiographic axial spondyloarthritis (NR-AxSpA), plaque psoriasis (PsO), psoriatic arthritis (PsA), rheumatoid arthritis (RA), and ulcerative colitis (UC). Sequences included three biological or disease-modifying treatments, followed by best supportive care. Disease-specific response measures were selected on the basis of clinical relevance, data availability, and data quality. Efficacy was differentiated between biologic-naïve and experienced populations, where possible, using published network meta-analyses and real-world data. All possible treatment sequences, based on reimbursement as of December 2022 in Italy (analyses' base country), were simulated. RESULTS: Sequences with the best outcomes consistently employed the most efficacious therapies earlier in the treatment pathway. Improvements to prescribing practice are possible in all diseases; however, most notable was UC, where the per-patient 3-year average treatment failure was 37.3% higher than optimal. The results focused on the three most crowded and prevalent immunological sub-condition diseases in dermatology, rheumatology, and gastroenterology: PsO, RA, and UC, respectively. By prescribing from within the top 20% of the most efficacious sequences, the model found a 15.1% reduction in treatment failures, with a 1.59% increase in drug costs. CONCLUSIONS: Prescribing more efficacious treatments earlier provides a greater opportunity to improve patient outcomes and minimizes treatment failures.

Characterizing the relationship between gonadotropin releasing hormone (GnRH), kisspeptin, and RFamide related peptide 3 (RFRP-3) neurons in the equine hypothalamus across the estrous cycle and in the anovulatory seasons.

To understand better the role that kisspeptin plays in regulating seasonal and estrous cycle changes in the mare, this study investigated the number, location and interactions between GnRH, kisspeptin and RFRP-3 neurons in the equine hypothalamus. Hypothalami were collected from mares during the non-breeding season, vernal transition and various stages of the breeding season. Fluorescent immunohistochemistry was used to label the neuropeptides of interest. GnRH cells were observed primarily in the arcuate nucleus (ARC), while very few labeled cells were identified in the pre-optic area (POA). Kisspeptin cells were identified primarily in the ARC, with a small number of cells observed dorsal to the ARC, surrounding the third ventricle (3V). The mean number of kisspeptin cells varied between animals and typically showed no pattern associated with season or stage of estrous cycle, but a seasonal difference was identified in the ARC population. Small numbers of RFRP-3 cells were observed in the ARC, ventromedial hypothalamus (VMH) and dorsomedial hypothalamus (DMH). The mean number of RFRP-3 cells appeared higher in pre-ovulatory animals compared to all other stages. The percentage of GnRH cell bodies with kisspeptin appositions did not change with season or stage of estrous cycle. The percentage of kisspeptin cells receiving inputs from RFRP-3 fibers did not vary with season or stage of estrous cycle. These interactions suggest the possibility of the presence of an ultra-short loop feedback system between these three peptides. The changes in RFRP-3 neurons suggest the possibility of a role in the regulation of reproduction in the horse, but it is unlikely to be as a gonadotropin inhibitory factor.

Rendimiento diagnóstico de un nuevo software de aprendizaje profundo para corrección de atenuación en la imagen de perfusión miocárdica utilizando una cámara CZT cardiodedicada. Experiencia en la práctica clínica / Diagnostic performance of a novel deep learning attenuation correction software for MPI using a cardio dedicated CZT camera: Experience in the clinical practice

Objetivo Evaluar el rendimiento diagnóstico de un nuevo software de aprendizaje profundo para corrección de atenuación (SAPCA) en imágenes de perfusión miocárdica (IPM) utilizando una cámara cardiodedicada de cadmio-cinc-telurio (CZT) con correlación con angiografía coronaria (AC) para el diagnóstico de enfermedad arterial coronaria (EAC) en una población de alto riesgo. Métodos Estudio retrospectivo de 300 pacientes (196 varones [65%], edad media de 68 años) desde septiembre de 2014 hasta octubre de 2019. Posteriormente realizaron una IPM, seguida de AC dentro de los 6 meses posteriores a la IPM. La probabilidad media pretest para EAC según los criterios de la Sociedad Europea de Cardiología fue del 37%. La IPM se realizó en una cámara CZT cardio dedicada (D-SPECT® Spectrum Dynamics) usando un protocolo de 2 días, de acuerdo con las guías de la Sociedad Europea de Medicina Nuclear (EANM). La IPM fue evaluada con y sin el SAPCA. Resultados La precisión diagnóstica global de la IPM sin el SAPCA para identificar pacientes con cualquier EAC obstructiva en la AC fue del 87%, sensibilidad del 94%, especificidad del 57%, valor predictivo positivo del 91% y valor predictivo negativo del 64%. Utilizando el SAPCA, la precisión diagnóstica global fue del 90%, la sensibilidad del 91%, la especificidad del 86%, el valor predictivo positivo del 97% y el valor predictivo negativo del 66%. Conclusión El uso del novel SAPCA mejora el rendimiento diagnóstico de la IPM usando la cámara CZT D-SPECT®, especialmente reduciendo el número de resultados falsos positivos al reducir los artefactos (AU)

urpose To evaluate the diagnostic performance of a novel deep learning attenuation correction software (SAPCA) for myocardial perfusion imaging (MPI) using a cadmium-zinc-telluride (CZT) cardio dedicated camera with invasive coronary angiography (ICA) correlation for the diagnosis of coronary artery disease (CAD) in a high-risk population. Methods Retrospective study of 300 patients (196 males [65%], mean age 68 years) from September 2014 to October 2019 undergoing MPI, followed by ICA and evaluated by means of quantitative angiography software, within six months after the MPI. The mean pre-test probability score for coronary disease according to the European Society of Cardiology criteria was 37% for the whole cohort. The MPI was performed in a dedicated CZT cardio camera (D-SPECT® Spectrum Dynamics) with a two-day protocol, according to the European Association of Nuclear Medicine guidelines. MPI was retrospectively evaluated with and without the SAPCA. Results The overall diagnostic accuracy of MPI without SAPCA to identify patients with any obstructive CAD at ICA was 87%, Sensitivity 94%, Specificity 57%, positive predictive value 91% and negative predictive value 64%. Using SAPCA the overall diagnostic accuracy was 90%, sensitivity 91%, specificity 86%, positive predictive value 97% and negative predictive value 66%. Conclusion Use of the novel SAPCA enhances performance of the MPI using the CZT D-SPECT® camera and achieves improved results, especially avoiding artefacts and reducing the number of false positive results (AU)

Disentangling Population Health Management Initiatives in Diabetes Care: A Scoping Review.

Introduction: Population Health Management (PHM) focusses on keeping the whole population as healthy as possible. As such, it could be a promising approach for long-term health improvement in type 2 diabetes. This scoping review aimed to examine the extent to which and how PHM is used in the care for people with type 2 diabetes. Methods: PubMed, Web of Science, and Embase were searched between January 2000 and September 2021 for papers on self-reported PHM initiatives for type 2 diabetes. Eligible initiatives were described using the analytical framework for PHM. Results: In total, 25 studies regarding 18 PHM initiatives for type 2 diabetes populations were included. There is considerable variation in whether and how the PHM steps are operationalized in existing PHM initiatives. Population identification, impact evaluation, and quality improvement processes were generally part of the PHM initiatives. Triple Aim assessment and risk stratification actions were scarce or explained in little detail. Moreover, cross-sector integration is key in PHM but scarce in practice. Conclusion: Operationalization of PHM in practice is limited compared to the PHM steps described in the analytical framework. Extended risk stratification and integration efforts would contribute to whole-person care and further health improvements within the population.

Evaluation of Healthcare Utilisation and Expenditures in Persons with Type 2 Diabetes Undergoing Bariatric-Metabolic Surgery.

PURPOSE: Changes in healthcare utilisation and expenditures after bariatric-metabolic surgery (BMS) for people with type 2 diabetes mellitus (T2DM) are unclear. We used the Dutch national all-payer claims database (APCD) to evaluate utilisation and expenditures in people with T2DM who underwent BMS. METHODS: In this cohort study, patients with T2DM who had BMS in 2016 were identified in the APCD. This group was matched 1:2 to a control group with T2DM who did not undergo BMS based on age, gender and healthcare expenditures. Data on healthcare expenditures and utilisation were collected for 2013-2019. RESULTS: In total, 1751 patients were included in the surgery group and 3502 in the control group. After BMS, total median expenditures in the surgery group stabilised (€ 3156 to € 3120) and increased in the control group (€ 3174 to € 3434). Total pharmaceutical expenditures decreased 28% in the surgery group (€957 to €494) and increased 55% in the control group (€605 to €936). In the surgery group, 67.1% did not use medication for T2DM in 2019 compared to 13.3% in the control group. Healthcare use for microvascular complications increased in the control group, but not in the surgery group. CONCLUSION: BMS in people with T2DM stabilises healthcare expenditures and decreases medication use and care use for microvascular complications. In contrast, healthcare use and expenditures in T2DM patients who do not undergo surgery gradually increase over time. Due to the progressive nature of T2DM, it is expected that these differences will become larger in the long-term.

Preclinical safety evaluation of continuous UV-A lighting in an operative setting.

BACKGROUND: Germicidal ultraviolet (UV-C) light has been shown as an effective modality for disinfection in laboratory settings and in the operative room. Traditionally, short-wavelength UV-C devices, which have previously been shown to cause DNA damage, are utilized only for disinfection in pre- and post-operative settings and are not continuously active during operations. Continuous use of intraoperative UV light has potential to decrease pathogens and subsequent surgical site infections (SSIs), which arise in approximately 5-15% of operative cases. SSIs are a significant determinant of patient morbidity, readmission rates, and overall cost. Therefore, a method of UV light disinfection with a low risk of DNA damage is needed so that greater antimicrobial protection can be afforded to patients during the entirety of their surgical procedures. A new disinfection device that harnesses longer-wavelength UV-A light to disinfect the surgical field throughout the entirety of the procedure, including pre- and post-operation has been developed. METHODS: This study aimed to determine if UV-A light administered intraoperatively was safe, as defined by the minimal presence of DNA damage and safe amounts of reflection upon medical personnel. Using in vitro models, we examined the differential impacts of UV-C and UV-A light on DNA damage and repair pathways. In a murine model, we looked at the production of DNA damage photoproduction in relation to UV-A versus UV-C exposure. RESULTS: Our results show UV-A light does not induce a significant amount of DNA damage at the cellular or tissue level. Furthermore, a preclinical porcine study showed that surgical personnel were exposed to safe levels of UV-A irradiance from an overhead UV-A light used during an operation. The amount of UV-A transmitted through surgical personal protective equipment (PPE) also remained within safe levels. CONCLUSIONS: In conclusion, we found that UV-A may be safe for intraoperative use.

Placental characteristics and neonatal weights among women with malaria-preeclampsia comorbidity and healthy pregnancies.

BACKGROUND: Malaria and preeclampsia are leading causes of maternal morbidity and mortality in sub-Saharan Africa. They contribute significantly to poor perinatal outcomes like low neonatal weight by causing considerable placental morphological changes that impair placental function. Previous studies have described the effects of either condition on the placental structure but the structure of the placenta in malaria-preeclampsia comorbidity is largely understudied despite its high burden. This study aimed to compare the placental characteristics and neonatal weights among women with malaria-preeclampsia comorbidity versus those with healthy pregnancies. METHODOLOGY: We conducted a retrospective cohort study among 24 women with malaria-preeclampsia comorbidity and 24 women with healthy pregnancies at a County Hospital in Western Kenya. Neonatal weights, gross and histo-morphometric placental characteristics were compared among the two groups. RESULTS: There was a significant reduction in neonatal weights (P<0.001), placental weights (P = 0.028), cord length (P<0.001), and cord diameter (P<0.001) among women with malaria-preeclampsia comorbidity compared to those with healthy pregnancies. There was also a significant reduction in villous maturity (P = 0.016) and villous volume density (P = 0.012) with increased villous vascularity (P<0.007) among women with malaria-preeclampsia comorbidity compared to those with healthy pregnancies. CONCLUSION: Placental villous maturity and villous volume density are significantly reduced in patients with malaria-preeclampsia comorbidity with a compensatory increase in villous vascularity. This leads to impaired placental function that contributes to lower neonatal weights.

Rendimiento diagnóstico de diferentes protocolos de estrés cardiaco usados en imagen de perfusión miocárdica para el diagnóstico de enfermedad coronaria usando una cámara de cadmio-zinc-telurio con correlación con angiografía coronaria / Diagnostic performance of different cardiac stress protocols for myocardial perfusion imaging for the diagnosis of coronary artery disease using a cadmium-zinc-telluride camera with invasive coronary angiography correlation

Objetivo Evaluar el rendimiento diagnóstico de tres protocolos diferentes de estrés cardiaco utilizados en imagen de perfusión miocárdica (IPM), usando una cámara de cadmio-zinc-telurio (CZT) en correlación con angiografía coronaria (AC) para el diagnóstico de enfermedad arterial coronaria (EAC) en una población de alto riesgo. Métodos Estudio retrospectivo realizado en 263 pacientes (96 mujeres y 167 varones, edad media 68 años), de los cuales 119 realizaron una prueba de estrés con bicicleta (PEB), 113 una prueba de estrés farmacológica (PEF) y 31 una combinación de ambas (PEC), entre septiembre de 2014 y diciembre de 2018. Posteriormente realizaron una IPM, seguida de AC dentro de los seis meses posteriores a la IPM. La probabilidad preprueba media para EAC según los criterios de la Sociedad Europea de Cardiología fue de 36%. La IPM se realizó en una cámara CZT cardio dedicada (D-SPECT Spectrum Dynamics) con un protocolo de dos días, de acuerdo con las guías de la Asociación Europea de Medicina Nuclear (EANM). Resultados No se observaron diferencias significativas entre los diferentes protocolos de estrés en términos de precisión diagnóstica (PEB 85%, PEF 88%, PEC 84%). La exactitud diagnóstica general de IPM para identificar pacientes con cualquier EAC obstructiva en AC fue de 86%, sensibilidad de 93%, especificidad de 54%, VPP de 90% y VPN de 63%. Conclusión La cámara CZT D-SPECT logra resultados generales satisfactorios en el diagnóstico de la EAC, sin encontrar diferencias significativas en el rendimiento diagnóstico cuando la prueba de esfuerzo se realizó como PEB, PEF o PEC. (AU)

Purpose To evaluate the diagnostic performance of three different cardiac stress protocols for myocardial perfusion imaging (MPI) using a cadmium-zinc-telluride (CZT) camera with invasive coronary angiography (ICA) correlation for the diagnosis of coronary artery disease in a high risk population. Methods Retrospective study of 263 patients (96 women and 167 males, mean age 68 years) from which 119 patients performed a bicycle stress test (BST), 113 pharmacological stress test (PST) and 31 a combination of the two (CST) between September 2014 and December 2018. The patients then underwent myocardial perfusion imaging (MPI), followed by ICA and evaluated by means of quantitative angiography software, within six months after the MPI. The mean pre-test probability score for coronary disease according to the European Society of Cardiology criteria was 36% for the whole population. The MPI was performed in a dedicated CZT cardio camera (D-SPECT Spectrum Dynamics) with a two-day protocol, according to the European Association of Nuclear Medicine guidelines. Results No significant difference was observed between the three stress protocols in terms of diagnostic accuracy (BST 85%, PST 88% and CST 84%). The overall diagnostic accuracy of MPI to identify patients with any obstructive CAD at ICA was 86%, Sensitivity 93%, Specificity 54%, PPV 90% and NPV 63%. Conclusion The CZT D-SPECT camera achieves overall satisfactory results in the diagnosis of CAD, observing no significant differences in the diagnostic performance when the stress test was performed as a BST, PST or CST (AU)

Management of neuroendocrine tumor liver metastases.

BACKGROUND: Neuroendocrine Tumors (NETs) are a group of tumors that arise from neuroendocrine cells, and are increasing in incidence worldwide. These tumors often metastasize to the liver, and management of these neuroendocrine tumor liver metastases (NELMs) requires a multi-disciplinary approach. We aim to provide a comprehensive update for treatment of NELMs. METHODS: We completed a comprehensive systemic review of papers involving the diagnosis, treatment, and outcomes of NELMs. We identified 1612 records via Scopus database literature search. Two independent authors reviewed these records, with 318 meeting criteria for inclusion in the final systemic review. RESULTS: Primary tumor resection with resection of liver metastases is the treatment of choice for patients with NELMs. Liver-directed therapies and liver transplantation can be considered for patients with unresectable liver metastases. Systemic medical therapy is used for managing tumor burden and symptoms caused by NELMs. CONCLUSIONS: Advancement in liver-directed and targeted systemic therapies provide improved options for patients with unresectable tumors. Given the complexity of NELMs, management of NELMs necessitates multidisciplinary teams at comprehensive health centers.

Reductions in anxiety and depression symptoms in a subset of outpatients with problematic substance use who received ketamine-assisted psychotherapy: a two-year retrospective chart review.

Objective: Assess changes in symptoms of anxiety, depression, and psychosocial or spiritual distress before and after ketamine-assisted psychotherapy (KAP) in individuals with problematic substance use (PSU). Methods: A retrospective chart review was performed on participant data from two five-year prospective outcomes studies: the AIMS Medical Outcomes Study (AMOS) and the AIMS Cancer Outcomes Study (ACOS). The efficacy of KAP for anxiety, depression, and psychosocial or spiritual well being was assessed in patients with current, past, or high risk of substance use disorder. Validated psychometrics utilized were Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and the National Institute of Health - Healing Experiences of All Life Stressors (NIH-HEALS) questionnaires. Results: Between November 1, 2020 and October 31, 2022, a total of 18 patients identified with problematic substance use completed at least one KAP session and at least one baseline and post-KAP metric questionnaire. The PSU subpopulation average score changes were as follows: GAD-7 (-6.71 ± 9.15, n = 14); PHQ-9 (-7.44 ± 5.42, n = 16); and NIH-HEALS (5.13 ± 13.64, n = 15). The average score changes for the KAP population of enrolled subjects were as follows: GAD-7 (-2.45 ± 6.01, n = 104); PHQ-9 (-3.02 ± 6.01, n = 111); and NIH-HEALS (2.93 ± 11.91, n = 86). A comparison of average score changes (p < 0.05) between the PSU subpopulation and KAP population were as follows: GAD-7 (0.0219, 95% C.I. 1.37-8.11); PHQ-9 (0.0062, 95% C.I. 1.28-7.56); and NIH-HEALS (0.5197, 95% C.I. 8.96-4.56). For patients with PSU, results demonstrate statistically significant improvements in anxiety and depression symptoms after at least one KAP session. Average NIH-HEALS scores increased, though not by a statistically significant amount. Compared to the general population of enrolled KAP patients during this period, patients with PSU reported significantly greater average reductions in GAD-7 and PHQ-9 scores. Conclusion: Undergoing one to six ketamine-assisted psychotherapy (KAP) sessions was associated with improved anxiety and depression ratings in patients with problematic substance use. Two-thirds of participants also experienced improved psychosocial and spiritual well-being. The use of KAP may be important to consider as a therapy for reducing anxiety and depression symptoms in patients with problematic substance use.

Structural basis for respiratory syncytial virus and human metapneumovirus neutralization.

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) continue to be a global burden to infants, the elderly, and immunocompromised individuals. In the past ten years, there has been substantial progress in the development of new vaccine candidates and therapies against these viruses. These advancements were guided by the structural elucidation of the major surface glycoproteins for these viruses, the fusion (F) protein and attachment (G) protein. The identification of immunodominant epitopes on the RSV F and hMPV F proteins has expanded current knowledge on antibody-mediated immune responses, which has led to new approaches for vaccine and therapeutic development through the stabilization of pre-fusion constructs of the F protein and pre-fusion-specific monoclonal antibodies with high potency and efficacy. In this review, we describe structural characteristics of known antigenic sites on the RSV and hMPV proteins, their influence on the immune response, and current progress in vaccine and therapeutic development.

HPV vaccination acceptance and perceptions related to fertility and population control in the Gambia: An anthropological analysis.

This qualitative study using in-depth interviews and focus group discussions is the first to investigate HPV vaccination in The Gambia; it provides an in-depth analysis of uptake, knowledge, and perceptions of HPV vaccination as well as trust in Ministry of Health vaccination advice. Despite high uptake rates, knowledge of HPV vaccination was low, and the most prominent concern was that the vaccine could cause infertility or is a form of population control. Holistic approaches to addressing HPV vaccine concerns relating to fertility that consider socio-political contexts, including colonial histories, could lead to more positive vaccine perceptions, empowered decisions and to increasing vaccine uptake rates in The Gambia and elsewhere.

Serum miRNA profiles are altered in patients with primary sclerosing cholangitis receiving high-dose ursodeoxycholic acid.

Background & Aims: Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic liver disease that can lead to end-stage liver disease and cholangiocarcinoma. High-dose ursodeoxycholic acid (hd-UDCA, 28-30 mg/kg/day) was evaluated in a previous multicentre, randomised placebo-controlled trial; however, the study was discontinued early because of increased liver-related serious adverse events (SAEs), despite improvement in serum liver biochemical tests. We investigated longitudinal changes in serum miRNA and cytokine profiles over time among patients treated with either hd-UDCA or placebo in this trial as potential biomarkers for PSC and response to hd-UDCA, as well as to understand the toxicity associated with hd-UDCA treatment. Methods: Thirty-eight patients with PSC were enrolled in a multicentred, randomised, double-blinded trial of hd-UDCA vs. placebo. Results: Significant alterations in serum miRNA profiles were found over time in both patients treated with hd-UDCA or placebo. Additionally, there were striking differences between miRNA profiles in patients treated with hd-UDCA compared with placebo. In patients treated with placebo, the changes in concentration of serum miRNAs miR-26a, miR-199b-5p, miR-373, and miR-663 suggest alterations of inflammatory and cell proliferative processes consistent with disease progression. However, patients treated with hd-UDCA exhibited a more pronounced differential expression of serum miRNAs, suggesting that hd-UDCA induces significant cellular miRNA changes and tissue injury. Pathway enrichment analysis for UDCA-associated miRNAs suggested unique dysregulation of cell cycle and inflammatory response pathways. Conclusions: Patients with PSC have distinct miRNAs in the serum and bile, although the implications of these unique patterns have not been studied longitudinally or in relation to adverse events related to hd-UDCA. Our study demonstrates marked changes in miRNA serum profiles with hd-UDCA treatment and suggests mechanisms for the increased liver toxicity with therapy. Impact and implications: Using serum samples from patients with PSC enrolled in a clinical trial comparing hd-UDCA with placebo, our study found distinct miRNA changes in patients with PSC who are treated with hd-UDCA over a period of time. Our study also noted distinct miRNA patterns in patients who developed SAEs during the study period.

Data integration reveals dynamic and systematic patterns of breeding habitat use by a threatened shorebird.

Incorporating species distributions into conservation planning has traditionally involved long-term representations of habitat use where temporal variation is averaged to reveal habitats that are most suitable across time. Advances in remote sensing and analytical tools have allowed for the integration of dynamic processes into species distribution modeling. Our objective was to develop a spatiotemporal model of breeding habitat use for a federally threatened shorebird (piping plover, Charadrius melodus). Piping plovers are an ideal candidate species for dynamic habitat models because they depend on habitat created and maintained by variable hydrological processes and disturbance. We integrated a 20-year (2000-2019) nesting dataset with volunteer-collected sightings (eBird) using point process modeling. Our analysis incorporated spatiotemporal autocorrelation, differential observation processes within data streams, and dynamic environmental covariates. We evaluated the transferability of this model in space and time and the contribution of the eBird dataset. eBird data provided more complete spatial coverage in our study system than nest monitoring data. Patterns of observed breeding density depended on both dynamic (e.g., surface water levels) and long-term (e.g., proximity to permanent wetland basins) environmental processes. Our study provides a framework for quantifying dynamic spatiotemporal patterns of breeding density. This assessment can be iteratively updated with additional data to improve conservation and management efforts, because reducing temporal variability to average patterns of use may cause a loss in precision for such actions.