Balanced anesthesia in pigeons (Columba livia): a protocol that ensures stable vital parameters and feasibility during long surgeries in cognitive neuroscience.

In neuroscience, numerous experimental procedures in animal models require surgical interventions, such as the implantation of recording electrodes or cannulas before main experiments. These surgeries can take several hours and should rely on principles that are common in the field of research and medicine. Considering the characteristics of the avian respiratory physiology, the development of a safe and replicable protocol for birds is necessary to minimize side effects of anesthetic agents, circumvent technical limitations due to the insufficient availability of patient monitoring, and to maintain stable intraoperative anesthesia. Through the consistent and responsible implementation of the three R principle of animal welfare in science ("Replace, Reduce, Refine"), we aimed to optimize experimental methods to minimize the burden on pigeons (Columba livia) during surgical procedures. Here, surgeries were conducted under balanced anesthesia and perioperative monitoring of heart rate, oxygen saturation, body temperature, and the reflex state. The protocol we developed is based on the combination of injectable and inhalative anesthetic drugs [ketamine, xylazine, and isoflurane, supported by the application of an opiate for analgesia (e.g., butorphanol, buprenorphine)]. The combination of ketamine and xylazine with a pain killer is established in veterinary medicine across a vast variety of species. Practicability was verified by survival of the animals, fast and smooth recovery quantified by clinical examination, sufficiency, and stability of anesthesia. Independent of painful stimuli like incision or drilling, or duration of surgery, vital parameters were within known physiological ranges for pigeons. Our approach provides a safe and conservative protocol for surgeries of extended duration for scientific applications as well as for veterinary medicine in pigeons which can be adapted to other bird species.

The maternal and newborn health eCohort to track longitudinal care quality: study protocol and survey development.

The MNH eCohort was developed to fill gaps in maternal and newborn health (MNH) care quality measurement. In this paper, we describe the survey development process, recruitment strategy, data collection procedures, survey content and plans for analysis of the data generated by the study. We also compare the survey content to that of existing multi-country tools on MNH care quality. The eCohort is a longitudinal mixed-mode (in-person and phone) survey that will recruit women in health facilities at their first antenatal care (ANC) visit. Women will be followed via phone survey until 10-12 weeks postpartum. User-reported information will be complemented with data from physical health assessments at baseline and endline, extraction from MNH cards, and a brief facility survey. The final MNH eCohort instrument is centered around six key domains of high-quality health systems including competent care (content of ANC, delivery, and postnatal care for the mother and newborn), competent systems (prevention and detection, timely care, continuity, integration), user experience, health outcomes, confidence in the health system, and economic outcomes. The eCohort combines the maternal and newborn experience and, due to its longitudinal nature, will allow for quality assessment according to specific risks that evolve throughout the pregnancy and postpartum period. Detailed information on medical and obstetric history and current health status of respondents and newborns will allow us to determine whether women and newborns at risk are receiving needed care. The MNH eCohort will answer novel questions to guide health system improvements and to fill data gaps in implementing countries.

Added knowledge: The MNH eCohort will answer novel questions and provide information on undermeasured dimensions of MNH care quality included continuity of care, system competence, and user experience.Global health impact for policy and action: The data generated will inform policy makers to develop strategies to improve adherence to standards of care and quality for mothers and newborns.

Introducing Casbah, Kronus, and MmasiCarm, Members of the Mycobacteriophage Subcluster B3.

Background: As part of a large science education effort, bacteriophages that lyse Mycobacterium smegmatis mc2155 continue to be discovered. Materials and Methods: Phages were isolated from soil samples from urban sites in the Northeastern United States. Their genomes were sequenced, assembled, and bioinformatically compared. Results: Three lytic siphoviruses belonging to subcluster B3 with high similarity to each other and other B3 mycobacteriophages were isolated. These phages contain double-stranded DNA genomes (68,754 to 69,495 bp) with high GC content (67.4-67.5%) and 102-104 putative protein coding genes. Notable features include a HicA-like toxin and 33 genes exclusive to subcluster B3. One phage had an intein in its terminase sequence. Conclusions: Genomic analyses of these phages provide insights into genome evolution and horizontal gene transfer (HGT). The networks for HGT are apparently vast and gene specific. Interestingly, a number of genes are found in both B3 and Gordonia DR phages.

Antenatal care quality and detection of risk among pregnant women: An observational study in Ethiopia, India, Kenya, and South Africa.

BACKGROUND: Antenatal care (ANC) is an essential platform to improve maternal and newborn health (MNH). While several articles have described the content of ANC in low- and middle-income countries (LMICs), few have investigated the quality of detection and management of pregnancy risk factors during ANC. It remains unclear whether women with pregnancy risk factors receive targeted management and additional ANC. METHODS AND FINDINGS: This observational study uses baseline data from the MNH eCohort study conducted in 8 sites in Ethiopia, India, Kenya, and South Africa from April 2023 to January 2024. A total of 4,068 pregnant women seeking ANC for the first time in their pregnancy were surveyed. We built country-specific ANC completeness indices that measured provision of 16 to 22 recommended clinical actions in 5 domains: physical examinations, diagnostic tests, history taking and screening, counselling, and treatment and prevention. We investigated whether women with pregnancy risks tended to receive higher quality care and we assessed the quality of detection and management of 7 concurrent illnesses and pregnancy risk factors (anemia, undernutrition, obesity, chronic illnesses, depression, prior obstetric complications, and danger signs). ANC completeness ranged from 43% in Ethiopia, 66% in Kenya, 73% in India, and 76% in South Africa, with large gaps in history taking, screening, and counselling. Most women in Ethiopia, Kenya, and South Africa initiated ANC in second or third trimesters. We used country-specific multivariable mixed-effects linear regression models to investigate factors associated with ANC completeness. Models included individual demographics, health status, presence of risk factors, health facility characteristics, and fixed effects for the study site. We found that some facility characteristics (staffing, patient volume, structural readiness) were associated with variation in ANC completeness. In contrast, pregnancy risk factors were only associated with a 1.7 percentage points increase in ANC completeness (95% confidence interval 0.3, 3.0, p-value 0.014) in Kenya only. Poor self-reported health was associated with higher ANC completeness in India and South Africa and with lower ANC completeness in Ethiopia. Some concurrent illnesses and risk factors were overlooked during the ANC visit. Between 0% and 6% of undernourished women were prescribed food supplementation and only 1% to 3% of women with depression were referred to a mental health provider or prescribed antidepressants. Only 36% to 73% of women who had previously experienced an obstetric complication (a miscarriage, preterm birth, stillbirth, or newborn death) discussed their obstetric history with the provider during the first ANC visit. Although we aimed to validate self-reported information on health status and content of care with data from health cards, our findings may be affected by recall or other information biases. CONCLUSIONS: In this study, we observed gaps in adherence to ANC standards, particularly for women in need of specialized management. Strategies to maximize the potential health benefits of ANC should target women at risk of poor pregnancy outcomes and improve early initiation of ANC in the first trimester.

Human monoclonal antibodies protect against viral-mediated pneumococcal superinfection.

Introduction: Community-acquired pneumonia (CAP) is a global health concern, with 25% of cases attributed to Streptococcus pneumoniae (Spn). Viral infections like influenza A virus (IAV), respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) increase the risk of Spn, leading to severe complications due to compromised host immunity. Methods: We evaluated the efficacy of an anti-PhtD monoclonal antibody (mAb) cocktail therapy (PhtD3 + 7) in improving survival rates in three viral/bacterial coinfection models: IAV/Spn, hMPV/Spn, and RSV/Spn. Results: The PhtD3 + 7 mAb cocktail outperformed antiviral mAbs, resulting in prolonged survival. In the IAV/Spn model, it reduced bacterial titers in blood and lungs by 2-4 logs. In the hMPV/Spn model, PhtD3 + 7 provided greater protection than the hMPV-neutralizing mAb MPV467, significantly reducing bacterial titers. In the RSV/Spn model, PhtD3 + 7 offered slightly better protection than the antiviral mAb D25, uniquely decreasing bacterial titers in blood and lungs. Discussion: Given the threat of antibiotic resistance, our findings highlight the potential of anti-PhtD mAb therapy as an effective option for treating viral and secondary pneumococcal coinfections.

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.

An Analysis on the Effect of Income Changes in the Resection of Early-Stage Pancreatic Adenocarcinoma.

INTRODUCTION: The impact of socioeconomic inequalities on cancer care and outcomes has been well recognized and the underlying causes are likely multifactorial. Income is regarded as a cornerstone of socioeconomic status and has been assumed to correlate with access to care. We therefore sought to investigate whether income and changes in income would affect the rate of patients undergoing surgical resection for early-stage pancreatic cancer. METHODS: Inflation-adjusted income data were obtained from the United States Census Bureau from 2010 to 2019. The cancer data were obtained from the SEER database. Counties present in both data sets were included in the analysis. Patients with stage I or II pancreatic cancer who underwent formal resection were deemed to have undergone appropriate surgical management. Patients were grouped into an early (2010-2014) and late (2015-2019) time period. RESULTS: The final analysis included 23968 patients from 173 counties across 11 states. The resection rate was 45.1% for the entire study and rose from 42.8% to 47.4% from the early to late time periods (P < .001). The median change in income between the two time periods was an increase by $2387. The rate of resection was not dependent on income class or income change in our study population. CONCLUSION: Our surgical care of pancreatic cancer is improving with more patients undergoing resection. In addition, there are now fewer disparities between patients of lower-income and higher-income groups with respect to receiving surgical intervention. This implies that our access to care has improved over the past decade. This is an encouraging finding with regards to reducing health care disparities.

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.

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.

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.

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.

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.

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.

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.

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.