Collaboration, coordination and communication as facilitators of transitions for patients with advanced cancer: a scoping review linked to the Pal-Cycles project.

BACKGROUND: Person-centred care is becoming increasingly recognised as an important element of palliative care. The current review syntheses evidence in relation to transitions in advanced cancer patients with palliative care needs. The review focuses on specific elements which will inform the Pal-Cycles programme, for patients with advanced cancer transitioning from hospital care to community care. Elements of transitional models for cancer patients may include, identification of palliative care needs, compassionate communication with the patient and family members, collaborative effort to establish a multi-dimensional treatment plan, review and evaluation of the treatment plan and identification of the end of life phase. METHODS: A scoping review of four databases (MEDLINE, EMBASE, CINAHL, PsycINFO) was conducted to identify peer-reviewed studies published from January 2013 to October, 2022. A further hand-search of references to locate additional relevant studies was also undertaken. Inclusion criteria involved cancer patients transitions of care with a minimum of two of components from those listed above. Studies were excluded if they were literature reviews, if transition of care was related to cancer survivors, involved non-cancer patients, had paediatric population, if the transition implied a change of therapy and or a lack of physical transit to a non-hospital place of care. This review was guided by Arksey and O'Malley's framework and narrative synthesis was used. RESULTS: Out of 5695 records found, 14 records were selected. Transition models identified: increases in palliative care consultations, hospice referrals, reduction in readmission rates and the ability to provide end of life care at home. Transition models highlight emotional and spiritual support for patients and families. No uniform model of transition was apparent, this depends on the healthcare system where it is implemented. CONCLUSIONS: The findings highlight the importance of collaboration, coordination and communication as central mechanisms for transitional model for patients with advanced cancer. This may require careful planning and will need to be tailored to the contexts of each healthcare system.

Pharmacological Treatment for Dialysis-Related Muscle Cramps: A Systematic Review.

BACKGROUND: Patients with end-stage renal disease undergoing dialysis suffer from muscle cramps, a prevalent and burdensome symptom for which there is a paucity of efficient and safe treatments. AIM: What is the efficacy and safety of pharmacological interventions for the treatment of dialysis-related muscle cramps? DESIGN: A systematic review was conducted in OVID, CINAHL, PubMed, Web of Science, and Central Cochrane databases up to August 25, 2023. DATA SOURCES: Experimental studies reporting on a pharmacological intervention for the treatment of dialysis-related muscle cramps were included. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis, and the studies quality was assessed with the RoB2 tool. RESULTS: A total of 4660 studies were retrieved, and 13 articles were included. The studies reported on nine interventions: vitamin C, vitamin E, vitamin K2, vitamin B7, dextrose solutions, gabapentin, sodium chloride, creatine monohydrate, and L-carnitine. The studies testing L-carnitine and creatine monohydrate were the only ones deemed to have a low risk of bias. Side effects were reported in only two trials, consisting primarily of gastrointestinal discomfort and hyperglycemia. Vitamins C and E are the two most studied interventions that showed positive results in reducing the frequency, severity, and duration of dialysis-related muscle cramps. L-carnitine is a promising intervention that warrants further investigation. CONCLUSION: Our review consolidates the existing evidence, elucidating the range of treatments along with their potential benefits and limitations. Future studies should uphold high-quality standards, incorporate patient-reported outcomes, and utilize well-defined, robust samples to improve patient care.

Palliative care national plan implementation through stakeholder analysis.

BACKGROUND: National palliative care plans depend upon stakeholder engagement to succeed. Assessing the capability, interest, and knowledge of stakeholders is a crucial step in the implementation of public health initiatives, as recommended by the World Health Organisation. However, utilising stakeholder analysis is a strategy underused in public palliative care. OBJECTIVE: To conduct a stakeholder analysis characterising a diverse group of stakeholders involved in implementing a national palliative care plan in three rural regions of an upper-middle-income country. METHODS: A descriptive cross-sectional study design, complemented by a quantitative stakeholder analysis approach, was executed through a survey designed to gauge stakeholders' levels of interest and capability in relation to five fundamental dimensions of public palliative care: provision of services, accessibility of essential medicines, palliative care education, financial support, and palliative care vitality. Stakeholders were categorised as promoters (high-power, high-interest), latent (high-power, low-interest), advocates (low-power, high-interest), and indifferent (low-power and low-interest). Stakeholder self-perceived category and knowledge level were also assessed. RESULTS: Among the 65 surveyed stakeholders, 19 were categorised as promoters, 34 as advocates, 9 as latent, and 3 as indifferent. Stakeholders' self-perception of their category did not align with the results of the quantitative analysis. When evaluated by region and palliative care dimensions the distribution of stakeholders was nonuniform. Palliative care funding was the dimension with the highest number of stakeholders categorised as indifferent, and the lowest percentage of promoters. Stakeholders categorised as promoters consistently reported a low level of knowledge, regardless of the dimension, region, or their level of interest. CONCLUSIONS: Assessing the capability, interest, and knowledge of stakeholders is a crucial step when implementing public health initiatives in palliative care. It allows for a data-driven decision-making process on how to delegate responsibilities, administer financial resources, and establish governance boards that remain engaged and work efficiently.

Type 1 diabetes prevention clinical trial simulator: Case reports of model-informed drug development tool.

Clinical trials seeking to delay or prevent the onset of type 1 diabetes (T1D) face a series of pragmatic challenges. Despite more than 100 years since the discovery of insulin, teplizumab remains the only FDA-approved therapy to delay progression from Stage 2 to Stage 3 T1D. To increase the efficiency of clinical trials seeking this goal, our project sought to inform T1D clinical trial designs by developing a disease progression model-based clinical trial simulation tool. Using individual-level data collected from the TrialNet Pathway to Prevention and The Environmental Determinants of Diabetes in the Young natural history studies, we previously developed a quantitative joint model to predict the time to T1D onset. We then applied trial-specific inclusion/exclusion criteria, sample sizes in treatment and placebo arms, trial duration, assessment interval, and dropout rate. We implemented a function for presumed drug effects. To increase the size of the population pool, we generated virtual populations using multivariate normal distribution and ctree machine learning algorithms. As an output, power was calculated, which summarizes the probability of success, showing a statistically significant difference in the time distribution until the T1D diagnosis between the two arms. Using this tool, power curves can also be generated through iterations. The web-based tool is publicly available: https://app.cop.ufl.edu/t1d/. Herein, we briefly describe the tool and provide instructions for simulating a planned clinical trial with two case studies. This tool will allow for improved clinical trial designs and accelerate efforts seeking to prevent or delay the onset of T1D.

Comparing the Need and Development of Pediatric Palliative Care in Mexico: A Geographical Analysis.

CONTEXT: The Global Atlas of Palliative Care (GAPC) ranked Mexico's palliative care services at a preliminary integration stage into mainstream healthcare services. However, this data does not reflect pediatric palliative care (PPC) development. OBJECTIVES: To analyze the current need and level of development of PPC within Mexico. METHODS: PPC need was estimated using causes of death associated with serious health-related suffering from national mortality data from the General Directorate of Health Information. The level of development was measured through six indicators involving access to PPC services and opioids, then classified using the GAPC development categories adapted to regional territories based on available data. RESULTS: In 2021, 37,444 children died in Mexico. Of those, 10,677 (28.29%) died from conditions with serious health-related suffering, averaging a need for PPC of 25/100,000 children. Out of Mexico's 32 states, two (6.2%) had no PPC activity (category 1), twenty (62.6%) were in a capacity-building phase (category 2), eight (25%) had isolated PPC provision (category 3a), while two (6.2%) had generalized PPC provision (category 3b). No state had early (category 4a) or advanced PPC integration (category 4b). Overall, Mexico was classified as category 2. CONCLUSIONS: PPC services are distributed unevenly across the country, leading to inequitable access to care and an inability to meet the needs of patients and families. There is a disparity between the level of development of adult palliative care services and the underdevelopment of PPC in Mexico. This information can help stakeholders guide the development of PPC where it is needed most.

DNA G-quadruplexes in the genome of Trypanosoma cruzi as potential therapeutic targets for Chagas disease: Dithienylethene ligands as effective antiparasitic agents.

Chagas disease is caused by the parasite Trypanosoma cruzi and affects over 7 million people worldwide. The two actual treatments, Benznidazole (Bzn) and Nifurtimox, cause serious side effects due to their high toxicity leading to treatment abandonment by the patients. In this work, we propose DNA G-quadruplexes (G4) as potential therapeutic targets for this infectious disease. We have found 174 PQS per 100,000 nucleotides in the genome of T. cruzi and confirmed G4 formation of three frequent motifs. We synthesized a family of 14 quadruplex ligands based in the dithienylethene (DTE) scaffold and demonstrated their binding to these identified G4 sequences. Several DTE derivatives exhibited micromolar activity against epimastigotes of four different strains of T. cruzi, in the same concentration range as Bzn. Compounds L3 and L4 presented remarkable activity against trypomastigotes, the active form in blood, of T. cruzi SOL strain (IC50 = 1.5-3.3 µM, SI = 25-40.9), being around 40 times more active than Bzn and displaying much better selectivity indexes.

Movement-related increases in subthalamic activity optimize locomotion.

The subthalamic nucleus (STN) is traditionally thought to restrict movement. Lesion or prolonged STN inhibition increases movement vigor and propensity, while optogenetic excitation has opposing effects. However, STN neurons often exhibit movement-related increases in firing. To address this paradox, STN activity was recorded and manipulated in head-fixed mice at rest and during self-initiated and self-paced treadmill locomotion. We found that (1) most STN neurons (type 1) exhibit locomotion-dependent increases in activity, with half firing preferentially during the propulsive phase of the contralateral locomotor cycle; (2) a minority of STN neurons exhibit dips in activity or are uncorrelated with movement; (3) brief optogenetic inhibition of the lateral STN (where type 1 neurons are concentrated) slows and prematurely terminates locomotion; and (4) in Q175 Huntington's disease mice, abnormally brief, low-velocity locomotion is associated with type 1 hypoactivity. Together, these data argue that movement-related increases in STN activity contribute to optimal locomotor performance.

Stroke associated with primary membranous nephropathy in a young adult: Case report / Evento cerebral isquémico asociado con nefropatía membranosa primaria en un adulto joven: reporte de caso

INTRODUCTION: Stroke in young individuals is becoming increasingly prevalent worldwide. Its causes can vary widely, so a thorough investigation by a multidisciplinary team is needed. Pinpointing the precise underlying pathology responsible for the stroke yields benefits for patients, particularly in recurrent events. CASE PRESENTATION: A 38-year-old man presented to the emergency department with symptoms suggestive of stroke, including right hemiparesis, dysarthria, ataxic gait, and right central facial palsy. The brain magnetic resonance image revealed an ischemic lesion located in the left basal ganglia and near the corona radiata. Following an extensive workup, a diagnosis of nephrotic was reached. Histopathology and the exclusion of secondary causes confirmed primary membranous nephropathy as the underlying condition. The patient underwent treatment tailored to address the specific glomerulopathy, along with anticoagulation therapy and immunosuppression as per current guidelines. Subsequent assessments showed stabilization of renal function, resolution of the edema, and the absence of new thromboembolic events during follow-up. CONCLUSION: The nephrotic syndrome should be recognized as a potential underlying cause of stroke in young patients and, therefore, it should be included in the differential diagnosis during the evaluation of patients with coagulopathies. Nephrotic syndrome screening may be done by conducting a simple urinalysis readily available in most healthcare facilities. This underlines the importance of considering renal pathology in the assessment of stroke etiologies, especially when coagulation abnormalities are present.

Introducción. Los eventos cerebrovasculares en los jóvenes son un problema creciente en todo el mundo. Su etiología puede ser variada y requieren un trabajo riguroso de un equipo multidisciplinario. La identificación de la enfermedad específica que conduce al ictus tiene un impacto beneficioso en los pacientes, especialmente en aquellos con eventos recurrentes. Presentación del caso. Se presenta el caso de un hombre de 38 años que acudió al servicio de urgencias con hemiparesia derecha, disartria, ataxia y parálisis facial central derecha. La resonancia magnética cerebral reveló una lesión isquémica localizada en los ganglios basales izquierdos, cerca de la corona radiada. Después de un estudio exhaustivo, se estableció el diagnóstico de síndrome nefrótico. No obstante, al analizar las características histopatológicas y descartar otras causas secundarias, el diagnóstico final fue una nefropatía membranosa primaria. El paciente recibió tratamiento específico para su glomerulopatía, anticoagulación e inmunosupresión según las guías vigentes. Durante el seguimiento, se encontró estabilización de la función renal, el edema se resolvió y no se identificó ningún nuevo evento tromboembólico. Conclusión. El síndrome nefrótico debe considerarse entre las posibles causas del ictus en pacientes jóvenes y debería tenerse en cuenta en los estudios de coagulopatías. El tamizaje de esta enfermedad requiere únicamente un uroanálisis, el cual está disponible en la mayoría de los centros de atención de salud.

Pheochromocytoma/paraganglioma type 5 syndrome as a cause of secondary hypertension in a Colombian patient: case report / Síndrome de feocromocitoma-paraganglioma de tipo 5 como causa de hipertensión arterial en una paciente colombiana: reporte de caso

Pheochromocytoma is a tumor derived from neural crest cells able to produce sympathomimetic substances and, hence, a particular clinical picture. It is responsible for less than 1% of high blood pressure cases, with an estimated incidence between 0.4 and 0.6 cases per 100,000 people each year, and an average survival of seven years. Pheochromocytoma is a solid tumor with a high genetic component, as heritability can reach 40%. Once diagnosed, its treatment and prognosis are partly conditioned by the associated pathogenic variants that can be documented, especially those related to RET, SDHx, VHL, and NF1 genes. We present the case of a young woman with abdominal pain and high blood pressure, who was found to have a pheochromocytoma. Genetic testing detected a rare and recently discovered pathogenic variant: the SDHA:c.1A>C (p.Met1Leu). The patient responded adequately to the surgical treatment and continued the follow-up without documented recurrences. The diagnostic approach for pheochromocytoma patients must start with a clinical suspicion, followed by metabolite measurement in blood and urine, and finally, imaging. Currently, technology development allows precision medicine applicability. In this case of pheochromocytoma, recent developments in precision medicine resulted in the detection of associated genetic components involving the patient and her family. Adequate screening of the index patient is required for documenting pathogenic variants and better characterizing the disease.

El feocromocitoma es un tumor derivado de las células de la cresta neural con la capacidad de producir sustancias simpaticomiméticas y, por ende, un cuadro clínico particular. Causa menos del 1 % de los casos de hipertensión arterial sistémica y su incidencia se estima entre 0,4 y 0,6 casos por 100.000 personas cada año, con una supervivencia media de siete años. De todos los tumores sólidos, el feocromocitoma tiene un mayor componente genético, que puede heredarse hasta en el 40 % de los casos. Una vez diagnosticada la enfermedad, se debe definir el tratamiento y el pronóstico, en parte condicionados por las variantes genéticas asociadas, en especial RET, SDHx, VHL y NF1. Se presenta el caso de una mujer joven con dolor abdominal e hipertensión arterial sistémica, a quien se le diagnosticó feocromocitoma. Al secuenciar el exoma, se identificó una variante patogénica extremadamente rara y de reciente descubrimiento: SDHA: c.1A>C (p.Met1Leu). La paciente respondió adecuadamente al tratamiento quirúrgico y continuó en seguimiento sin recurrencias. El abordaje diagnóstico de los pacientes con feocromocitoma comienza con la sospecha clínica, seguida de la medición de determinados metabolitos en sangre y orina, y, finalmente, los estudios de imagenología. Los desarrollos tecnológicos actuales permiten la aplicación de la medicina de precisión en este campo. En este caso de feocromocitoma, se identificó un componente genético importante que no solo afecta al paciente, sino también, a sus familiares. La tamización adecuada del caso índice permite identificar mutaciones y caracterizar mejor la enfermedad.

Interoceptive awareness in a clinical setting: the need to bring interoceptive perspectives into clinical evaluation.

Interoceptive awareness (IA) is crucial to understanding mental health. The Multidimensional Assessment of Interoceptive Awareness (MAIA) scale, available in approximately 30 languages, has gained global recognition for its research applicability. This review highlights the critical importance of integrating IA evaluation in clinical settings, advocating for the MAIA scale's potential as a screening tool. Through an examination of academic databases, including Scopus, PubMed, Google Scholar, and J-STOR, our analysis spans seven mental health domains: eating disorders (ED), depression, stress, anxiety, autism spectrum disorder (ASD), chronic pain, and suicide ideation (SI). Thirty-eight studies showed links between several dimensions of IA with different disorders. That is, ED was related to Body Trust and Self-Regulation; anxiety to Body Listening, Emotional Awareness, and Self-Regulation; depression to Noticing and Emotional Awareness; ASD to Trusting, Emotional Awareness, and Noticing; chronic pain to Not-Worrying and Self-Regulation; and SI with Trusting. These insights hold profound implications for both clinical practice and mental health research. Integrating IA assessments into standard clinical protocols has the potential to improve our understanding of pathology, enrich patient care, and enhance therapeutic strategies.

Structure-Activity Study on Substituted, Core-Extended, and Dyad Naphthalene Diimide G-Quadruplex Ligands Leading to Potent Antitrypanosomal Agents.

Several G-quadruplex nucleic acid (G4s) ligands have been developed seeking target selectivity in the past decade. Naphthalene diimide (NDI)-based compounds are particularly promising due to their biological activity and red-fluorescence emission. Previously, we demonstrated the existence of G4s in the promoter region of parasite genomes, assessing the effectiveness of NDI-derivatives against them. Here, we explored the biological activity of a small library of G4-DNA ligands, exploiting the NDI pharmacophore, against both Trypanosoma brucei and Leishmania major parasites. Biophysical and biological assays were conducted. Among the various families analyzed, core-extended NDIs exhibited the most promising results concerning the selectivity and antiparasitic effects. NDI 16 emerged as the most potent, with an IC50 of 0.011 nM against T. brucei and remarkable selectivity vs MRC-5 cells (3454-fold). Fascinating, 16 is 480-fold more potent than the standard drug pentamidine (IC50 = 5.3 nM). Cellular uptake and parasite localization were verified by exploiting core-extended NDI red-fluorescent emission.

Water temperature and microenvironmental factors predict the presence and detection of the snail host of Fasciola hepatica in Andean Patagonia.

The transmission of Fasciola hepatica occurs only where there are -or recently were- aquatic or amphibious snails of the Lymnaeidae family, the intermediate host of this parasite. Direct detection of these snails is time-consuming and imprecise, hindering accurate and detailed mapping of transmission risk. To identify which microenvironmental factors could be used as proxies for the occurrence of the lymnaeid snail Galba viator, a major intermediate host in South America, a total of 183 1-m2 quadrants across diverse water bodies in an endemic area in Andean Patagonia were manually timed-searched for snails and microenvironmental variables were registered. Data was analyzed using a Bayesian hierarchical occupancy model that assessed the effects of the microenvironmental variables on the presence of snails while considering imperfect snail detection. The model estimated that G. viator predominantly inhabits shallow aquatic environments, in the presence of grasses, where snails of the genus Biomphalaria are also detected, and with scarce tree canopy cover. Physical factors affecting occupancy presumably act as proxies for the average water temperature, while the temperature at the time of sampling was found to affect snail detectability. The identified variables are easy, fast, and inexpensive to measure, and can complement management decisions and risk maps based on coarser remote-sensing data, particularly relevant in a context of growing resistance to anthelminthic drugs.

Negative density dependence characterizes mutualistic interactions between birds and fruiting plants across latitudes.

Negative density dependence (NDD) in biotic interactions of interference such as plant-plant competition, granivory and herbivory are well-documented mechanisms that promote species' coexistence in diverse plant communities worldwide. Here, we investigated the generality of a novel type of NDD mechanism that operates through the mutualistic interactions of frugivory and seed dispersal among fruit-eating birds and plants. By sampling community-wide frugivory interactions at high spatial and temporal resolution in Pennsylvania, Puerto Rico, Peru, Brazil and Argentina, we evaluated whether interaction frequencies between birds and fruit resources occurred more often (selection), as expected, or below expectations (under-utilization) set by the relative fruit abundance of the fruit resources of each plant species. Our models considered the influence of temporal scales of fruit availability and bird phylogeny and diets, revealing that NDD characterizes frugivory across communities. Irrespective of taxa or dietary guild, birds tended to select fruits of plant species that were proportionally rare in their communities, or that became rare following phenological fluctuations, while they mostly under-utilized abundant fruit resources. Our results demonstrate that negative density-dependence in frugivore-plant interactions provides a strong equalizing mechanism for the dispersal processes of fleshy-fruited plant species in temperate and tropical communities, likely contributing to building and sustaining plant diversity. This article is part of the theme issue 'Diversitydependence of dispersal: interspecific interactions determine spatial dynamics'.

Bio-inspired computational memory model of the Hippocampus: An approach to a neuromorphic spike-based Content-Addressable Memory.

The brain has computational capabilities that surpass those of modern systems, being able to solve complex problems efficiently in a simple way. Neuromorphic engineering aims to mimic biology in order to develop new systems capable of incorporating such capabilities. Bio-inspired learning systems continue to be a challenge that must be solved, and much work needs to be done in this regard. Among all brain regions, the hippocampus stands out as an autoassociative short-term memory with the capacity to learn and recall memories from any fragment of them. These characteristics make the hippocampus an ideal candidate for developing bio-inspired learning systems that, in addition, resemble content-addressable memories. Therefore, in this work we propose a bio-inspired spiking content-addressable memory model based on the CA3 region of the hippocampus with the ability to learn, forget and recall memories, both orthogonal and non-orthogonal, from any fragment of them. The model was implemented on the SpiNNaker hardware platform using Spiking Neural Networks. A set of experiments based on functional, stress and applicability tests were performed to demonstrate its correct functioning. This work presents the first hardware implementation of a fully-functional bio-inspired spiking hippocampal content-addressable memory model, paving the way for the development of future more complex neuromorphic systems.

Correlación entre la edad cronológica y dental con los estadios de maduración vertebral / Correlation between chronological and dental age with vertebral maturation stages

Introducción: el desarrollo esquelético y dental es una condición determinante como factor principal de mala oclusión e influye en la evaluación, diagnóstico y planificación de los tratamientos de ortodoncia. Objetivo: estimar la correlación entre la edad cronológica y dental con los estadios de maduración vertebral. Material y métodos: la edad cronológica y dental se estimó por los métodos de Baccetti y el de Demirjian, con la lectura de 400 radiografías panorámicas y laterales de cráneo de 205 mujeres y 195 varones, con edades entre 4 y 17 años. La significancia estadística se estableció con el valor p < 0.05 del coeficiente de correlación de Pearson utilizando el programa SPSS v.24. Resultados: se observó un mayor porcentaje entre el estadio D de Demirjian con el estadio I de madurez de las vértebras cervicales (CVM) de Baccetti, seguido del estadio de calcificación dentaria E con el estadio CVM II. Además, existió una correlación moderada entre el método de Baccetti y el método de Demirjian en la pieza 37 (R2 = 0.3741) para la apreciación de la edad cronológica de un individuo. Conclusión: existe una buena correlación entre la edad cronológica y dental con los estadios de la maduración vertebral cervical, sin existir diferencias significativas por el sexo del individuo (AU)

Introduction: skeletal and dental development is a determining condition as the main factor of malocclusion and influences the evaluation, diagnosis, and planning of orthodontic treatments. Objective: to estimate the correlation between chronological and dental age with vertebral maturation stages. Material and methods: chronological and dental age was estimated by the Baccetti and Demirjian methods, with the reading of 400 panoramic and lateral skull radiographs of 205 women, and 195 men, aged between 4 and 17 years. Statistical significance was established with the value p < 0.05 of the Pearson correlation coefficient using the SPSS v.24 program. Results: a higher percentage was observed between Demirjian stage D with Baccetti cervical vertebral maturation (MVC) stage I, followed by dental calcification stage E with MVC stage II. In addition, there was a moderate correlation between the Baccetti method and the Demirjian method in piece 37 (R2 = 0.3741) for the assessment of the CD of an individual. Conclusion: there is a good correlation between chronological and dental age with the stages of cervical vertebral maturation, without significant differences due to the sex of the individual (AU)

Comparative 3D genome analysis between neural retina and retinal pigment epithelium reveals differential cis-regulatory interactions at retinal disease loci.

BACKGROUND: Vision depends on the interplay between photoreceptor cells of the neural retina and the underlying retinal pigment epithelium (RPE). Most genes involved in inherited retinal diseases display specific spatiotemporal expression within these interconnected retinal components through the local recruitment of cis-regulatory elements (CREs) in 3D nuclear space. RESULTS: To understand the role of differential chromatin architecture in establishing tissue-specific expression at inherited retinal disease loci, we mapped genome-wide chromatin interactions using in situ Hi-C and H3K4me3 HiChIP on neural retina and RPE/choroid from human adult donor eyes. We observed chromatin looping between active promoters and 32,425 and 8060 candidate CREs in the neural retina and RPE/choroid, respectively. A comparative 3D genome analysis between these two retinal tissues revealed that 56% of 290 known inherited retinal disease genes were marked by differential chromatin interactions. One of these was ABCA4, which is implicated in the most common autosomal recessive inherited retinal disease. We zoomed in on retina- and RPE-specific cis-regulatory interactions at the ABCA4 locus using high-resolution UMI-4C. Integration with bulk and single-cell epigenomic datasets and in vivo enhancer assays in zebrafish revealed tissue-specific CREs interacting with ABCA4. CONCLUSIONS: Through comparative 3D genome mapping, based on genome-wide, promoter-centric, and locus-specific assays of human neural retina and RPE, we have shown that gene regulation at key inherited retinal disease loci is likely mediated by tissue-specific chromatin interactions. These findings do not only provide insight into tissue-specific regulatory landscapes at retinal disease loci, but also delineate the search space for non-coding genomic variation underlying unsolved inherited retinal diseases.

Seasonal occurrence and individual variability of bull sharks, Carcharhinus leucas, in a marine reserve of the southwestern Gulf of California.

Background: Studying how the bull sharks aggregate and how they can be driven by life history traits such as reproduction, prey availability, predator avoidance and social interaction in a National Park such as Cabo Pulmo, is key to understand and protect the species. Methods: The occurrence variability of 32 bull sharks tracked with passive acoustic telemetry were investigated via a hierarchical logistic regression model, with inference conducted in a Bayesian framework, comparing sex, and their response to temperature and chlorophyll. Results: Based on the fitted model, occurrence probability varied by sex and length. Juvenile females had the highest values, whereas adult males the lowest. A strong seasonality or day of the year was recorded, where sharks were generally absent during September-November. However, some sharks did not show the common pattern, being detected just for a short period. This is one of the first studies where the Bayesian framework is used to study passive acoustic telemetry proving the potential to be used in further studies.