Uncovering multiscale structure in the variability of larval zebrafish navigation.

Animals chain movements into long-lived motor strategies, exhibiting variability across scales that reflects the interplay between internal states and environmental cues. To reveal structure in such variability, we build Markov models of movement sequences that bridges across time scales and enables a quantitative comparison of behavioral phenotypes among individuals. Applied to larval zebrafish responding to diverse sensory cues, we uncover a hierarchy of long-lived motor strategies, dominated by changes in orientation distinguishing cruising versus wandering strategies. Environmental cues induce preferences along these modes at the population level: while fish cruise in the light, they wander in response to aversive stimuli, or in search for appetitive prey. As our method encodes the behavioral dynamics of each individual fish in the transitions among coarse-grained motor strategies, we use it to uncover a hierarchical structure in the phenotypic variability that reflects exploration-exploitation trade-offs. Across a wide range of sensory cues, a major source of variation among fish is driven by prior and/or immediate exposure to prey that induces exploitation phenotypes. A large degree of variability that is not explained by environmental cues unravels motivational states that override the sensory context to induce contrasting exploration-exploitation phenotypes. Altogether, by extracting the timescales of motor strategies deployed during navigation, our approach exposes structure among individuals and reveals internal states tuned by prior experience.

Racial Disparities in Glioblastoma Genomic Alterations: A Comprehensive Analysis of a Multi-institution Cohort of 2,390 patients.

BACKGROUND: While molecular biomarkers have significantly advanced precision oncology in glioblastoma, the prevalence of these biomarkers by race remains underexplored. This study aims to characterize the genomic alterations in glioblastoma across Asian, Black, and White patients, offering insights into racial disparities that may influence treatment outcomes and disease progression. METHODS: Analyzing data from the AACR-GENIE database V13.0, this study examined 2,390 primary glioblastoma samples from unique patients. Genomic alterations in 566 cancer-related genes were assessed using targeted next-generation sequencing (NGS) panels from three large cancer institutes. The patient cohort included 112 Asians, 67 Blacks, and 2,211 Whites. Statistical significance of associations between genomic alterations and race was evaluated using the Chi-squared test, with the Benjamini-Hochberg method applied to control for multiple testing adjustments. RESULTS: Significant racial differences were observed in the frequency of genomic alterations. Asians exhibited a higher frequency of TP53 alterations (52.68%, P<0.001), Blacks showed more frequent alterations in NRAS (7.46%, P<0.001), MTOR (10.45%, P=0.039), and TET2 (8.96%, P=0.039), and Whites had a higher occurrence of PTEN alterations (48.67%, P=0.045). Additionally, Black patients had an elevated rate of RET deletions (14.29%, P<0.001). CONCLUSIONS: This study identifies significant racial disparities in the alteration frequencies of six key glioblastoma genes: NRAS, TP53, MTOR, TET2, PTEN, and RET. These findings underscore the need for racial considerations in glioblastoma treatment strategies and highlight potential avenues for targeted therapeutic interventions. Further research is needed to explore the clinical implications of these genomic disparities.

Retinal Dystrophies Associated With Peripherin-2: Genetic Spectrum and Novel Clinical Observations in 241 Patients.

Purpose: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene. Methods: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations. Results: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, or vitelliform macular dystrophy (11%), central areolar choroidal dystrophy (28%), pseudo-Stargardt pattern dystrophy (41%), and retinitis pigmentosa (25%). Symptom onset was earlier in retinitis pigmentosa as compared with pseudo-Stargardt pattern dystrophy (34 vs 44 years; P = 0.004). The median visual acuity was 0.18 logMAR (interquartile range, 0-0.54 logMAR) and 0.18 logMAR (interquartile range 0-0.42 logMAR) in the right and left eyes, respectively. ERG showed a significantly reduced amplitude across all components (P < 0.001) and a peak time delay in the light-adapted 30-Hz flicker and single-flash b-wave (P < 0.001). Twenty-two variants were novel. The central areolar choroidal dystrophy phenotype was associated with 13 missense variants. The remaining variants showed marked phenotypic variability. Conclusions: We described six distinct FAF phenotypes associated with variants in the PRPH2 gene. One FAF phenotype may have multiple ERG phenotypes, demonstrating a discordance between structure and function. Given the vast spectrum of PRPH2 disease our findings are useful for future clinical trials.

Uncovering multiscale structure in the variability of larval zebrafish navigation.

Animals chain movements into long-lived motor strategies, resulting in variability that ultimately reflects the interplay between internal states and environmental cues. To reveal structure in such variability, we build models that bridges across time scales that enable a quantitative comparison of behavioral phenotypes among individuals. Applied to larval zebrafish exposed to diverse sensory cues, we uncover a hierarchy of long-lived motor strategies, dominated by changes in orientation distinguishing cruising and wandering strategies. Environmental cues induce preferences along these modes at the population level: while fish cruise in the light, they wander in response to aversive (dark) stimuli or in search for prey. Our method enables us to encode the behavioral dynamics of each individual fish in the transitions among coarse-grained motor strategies. By doing so, we uncover a hierarchical structure to the phenotypic variability that corresponds to exploration-exploitation trade-offs. Within a wide range of sensory cues, a major source of variation among fish is driven by prior and immediate exposure to prey that induces exploitation phenotypes. However, a large degree of variability is unexplained by environmental cues, pointing to hidden states that override the sensory context to induce contrasting exploration-exploitation phenotypes. Altogether, our approach extracts the timescales of motor strategies deployed during navigation, exposing undiscovered structure among individuals and pointing to internal states tuned by prior experience.

Homeless people: a review of personality disorders.

Personality disorders in homeless people pose a challenge to the medical community and society, requiring specialized approaches for these super-difficult patients. The prevalence of personality disorders is higher in homeless populations than in the general population. However, there is a knowledge gap regarding personality disorders among people experiencing homelessness, and the implications of this lack of recognition are substantial. This paper provides a brief narrative review of personality disorders among homeless individuals. The primary importance and specificity of these disorders in this population remain unexplored. We searched PubMed and Web of Science databases in February and November 2023 using the keywords 'homeless' and 'personality disorder', and selected fifty-eight studies to be included in this literature review. The main themes of the results were personality disorders in homeless individuals and comorbid psychiatric disorders; risk factors and other psychological and behavioral data; clinical and intervention outcomes; and challenges linked to assessment, treatment, and intervention. The homeless population experiences significant diagnostic variability and the diagnosis of personality disorders is still evolving, contributing to difficulties in diagnosis, assessment, and treatment. A future challenge is to raise clinical awareness and optimize research knowledge, assessment, and intervention in personality disorders among homeless individuals with comorbid psychiatric disorders.

Detection of tick-borne pathogens in Rhipicephalus bursa ticks collected from the autochthonous Garrano breed of horses in Portugal.

The Garrano is a semi-feral horse breed native to several mountains in the northern Iberian Peninsula. Despite being endangered, this unique breed of pony has managed to survive in the wild and continues to be selectively bred, highlighting their remarkable resilience and adaptability to harsh environments. Wildlife plays a critical role in the survival of tick vectors in their natural habitats and the transfer of tick-borne pathogens, as they can serve as reservoir hosts for many agents and amplifiers for these vectors. The semi-feral lifestyle of the Garrano horses makes them particularly vulnerable to exposure to numerous tick species throughout the year. Therefore, the aim of this study was to investigate the occurrence of Anaplasma, Ehrlichia, Babesia, Theileria, and spotted fever rickettsiae in the Garrano horse ticks to obtain a knowledge of circulating agents in this host population. The collected ticks (n = 455) were identified as Rhipicephalus bursa. DNA specimens were organized in pools of 5 ticks, for molecular screening. Pools PCR results confirmed the presence of Candidatus Rickettsia barbariae (n = 12 for the ompB gene, n = 11 for the ompA gene and n = 6 for the gltA gene), Babesia bigemina (n = 1), Babesia caballi (n = 3), Theileria equi (n = 15) and Theileria haneyi (n = 1).These results confirm the circulation of an emerging rickettsial spotted fever group member, Candidatus R. barbariae, in R. bursa ticks. Our findings demonstrated that Candidatus R. barbariae co-circulates with B. bigemina and T. equi, which are vectored by R. bursa. We are reporting for the first time, the detection of T. haneyi among R. bursa ticks feeding in the Garrano horses in Portugal. Surveillance studies for tick-borne infections are essential to provide information that can facilitate the implementation of preventive and control strategies.

A review of published studies on virtual reality in sexuality research.

INTRODUCTION: Virtual reality (VR) technology contributes to greater approach of methodological safety to make ecological validity more feasible and a growing interest in sexuality behaviors. OBJECTIVES: The aim of this study was to show VR in the sexuality area by a comprehensive review of outcomes, offer a synthesis of the studies, and make a methodological quality assessment of finding results. A secondary goal was to investigate the effect of immersion on diverse sexual responses outcomes. METHODS: We designed a review based on a systematic review strategy describing types of studies, participants, data collection and outcomes; searched in 4 electronic databases (PubMed, EMBASE, PsycINFO, and SciELO), and made a full-text screening process. RESULTS: The study found 18 articles that met research criteria synthesized within 3 outcome groups: erection measures, level of immersion, and biomarker studies. Synthesis shows a lack of methodological aspects that impair results, such as description of methods from bias protection, randomization, or concealment. The literature still needs to improve its methodology, even though it already shows relevant data for intervention in sexual dysfunction, forensic psychiatry, sexual attraction, orientation, and use of pornography. CONCLUSION: Current methodological issues need better design to highlight relevant issues in sexuality with stronger quality of design, opening boundaries to new diagnostic or interventional technologies to sexual health.

The socioeconomic epidemiology of inherited retinal diseases in Portugal.

BACKGROUND: Inherited retinal diseases (IRDs) are a group of rare degenerative disorders of the retina that can lead to blindness from birth to late middle age. Knowing the target population and its resources is essential to better plan support measures. The aim of this study was to evaluate the socioeconomic characteristics of regions in Portugal where IRD patients reside to inform the planning of vision aid and rehabilitation intervention measures. RESULTS: This study included 1082 patients from 973 families, aged 3 to 92 years, with a mean age of 44.8 ± 18.1 years. Patients living with an IRD were identified in 190 of the 308 municipalities. According to this study, the estimated IRD prevalence in Portugal was 10.4 per 100,000 inhabitants, and by municipalities, it ranged from 0 to 131.2 per 100,000 inhabitants. Overall, regions with a higher prevalence of IRD have a lower population density (r=-0.371, p < 0.001), a higher illiteracy rate (r = 0.404, p < 0.001) and an overall older population (r = 0.475, p < 0.001). Additionally, there is a lower proportion of doctor per capita (r = 0.350, p < 0.001), higher social security pensions beneficiaries (r = 0.439, p < 0.001), worse water quality for human consumption (r=-0.194, p = 0.008), fewer audiences at the cinema (r=-0.315, p < 0.001) and lower proportion of foreign guests in tourist accommodations (r=-0.287, p < 0.001). CONCLUSION: The number of identified patients with IRD varied between regions. Using data from national statistics (PORDATA), we observed differences in socioeconomic characteristics between regions. Multiple targeted aid strategies can be developed to ensure that all IRD patients are granted full clinical and socioeconomic support.

Mutational spectrum and deep phenotyping in Pseudoxanthoma Elasticum: Findings from a Portuguese cohort.

INTRODUCTION: Pseudoxanthoma Elasticum (PXE) is a rare autosomal recessive disorder originated by disease-causing variants in ABCC6 gene. The purpose of this study was to characterize the genetic landscape, phenotypic spectrum and genotype-phenotype correlations in a Portuguese cohort of PXE patients. METHODS: Multicentric cross-sectional study conducted in patients with a clinical and genetic diagnosis of PXE. Patients were identified using the IRD-PT registry (www.retina.com.pt). Genotypes were classified into 3 groups: (1) two truncating variants, (2) two non-truncating variants, or (3) mixed variants. Deep phenotyping comprised a comprehensive ophthalmologic and systemic evaluation using the updated Phenodex Score (PS). RESULTS: Twenty-seven patients (23 families) were included. Sixteen different ABCC6 variants were identified, 7 of which are novel. The most prevalent variant was the nonsense variant c.3421C > T p.(Arg1141*) with an allele frequency of 18.5%. All patients exhibited ocular manifestations. Cutaneous manifestations were present in most patients (88.9%, n = 24/27). A PS score > E2 was strongly associated with worse visual acuity (B = -29.02; p = 0.001). No association was found between genotypic groups and cutaneous, vascular or cardiac manifestations. CONCLUSIONS: This study describes the genetic spectrum of patients with PXE for the first time in a Portuguese cohort. A total of 16 different variants in ABCC6 were found (7 of which are novel), thus highlighting the genotypic heterogeneity associated with this condition and expanding its mutational spectrum. Still, no major genotype-phenotype associations could be established.

Coronary Intravascular Lithotripsy Effectiveness and Safety in a Real-World Cohort.

Background: Coronary artery calcification is a predictor of adverse outcomes after percutaneous coronary intervention (PCI). Intravascular lithotripsy (IVL) is a promising tool for the treatment of calcified lesions. The aim of this study was to assess the effectiveness and safety of IVL. Methods: A single-center observational study of PCI procedure, with assessment of the outcomes of patients undergoing PCI using IVL, was performed. Angiographic procedural success was used as the primary effectiveness endpoint. The primary safety endpoint was defined as a composite of cardiac death, myocardial infarction and target vessel revascularization within 30 days. Results: A total of 111 patients were included. Indications for PCI spanned the spectrum of chronic (53.2%) and acute coronary syndromes (43%). Lesion preparation before IVL was performed with non-compliant (42%), cutting or OPN (14.4%) balloons and with atherectomy techniques in 11% of procedures. Intravascular imaging was used in 21.6% of procedures. The primary effectiveness endpoint was achieved in 100% and the primary safety endpoint in 3.6% of procedures. Peri-procedural complications were minimal and successfully resolved. Conclusions: IVL was an effective and safe technique for the treatment of calcified coronary lesions. These findings contribute to the growing body of evidence supporting the use of IVL in the management of these challenging scenarios.

Prognostic impact of hyperreflective foci in nonsyndromic retinitis pigmentosa.

PURPOSE: To evaluate the prognostic impact of hyperreflective foci (HRF) on spectral-domain optical coherence tomography (SD-OCT) in nonsyndromic retinitis pigmentosa (RP). METHODS: Retrospective, single-center cohort study including genetically-tested RP patients with a minimum follow-up of 24 months. Clinical data including demographics, genetic results and best-corrected visual acuity (BCVA) at baseline and follow-up were collected. Horizontal and vertical SD-OCT scans were analyzed by 2 independent graders. Outer nuclear layer (ONL) thickness and ellipsoid zone (EZ) width were manually measured in horizontal and vertical scans. HRF were classified according to location: outer retinal layers within the central 3mm (central-HRF), outer retinal layers beyond the central 3mm (perifoveal-HRF), and choroid (choroidal-HRF). Central macular thickness (CMT), central point thickness (CPT) and choroidal thickness (CT) at baseline and follow-up were also recorded. RESULTS: A total of 175 eyes from 94 RP patients (47.9% female, mean age 50.7±15.5 years) were included, with a mean follow-up of 29.24±7.17 months. Mean ETDRS (early treatment diabetic retinopathy study) BCVA decreased from 61.09±23.54 to 56.09±26.65 (p=0.082). At baseline, 72 eyes (41.1%) showed central-HRF, 110 eyes (62.9%) had perifoveal-HRF and 149 eyes (85.1%) exhibited choroidal-HRF. Central-HRF and perifoveal-HRF were associated with worse final BCVA, as well as greater BCVA deterioration (all p<0.0029). Only central-HRF were associated with a worse final CMT (p<0.001). Shorter EZ widths were associated with all types of HRF (p<0.05). Perifoveal and choroidal-HRF predicted smaller final EZ areas (p<0.01). CONCLUSION: HRF are highly prevalent in RP patients and appear to have a negative prognostic impact in visual function and EZ area.

Seaweeds as Nutraceutical Elements and Drugs for Diabetes Mellitus: Future Perspectives.

Diabetes mellitus is a chronic metabolic condition marked by high blood glucose levels caused by inadequate insulin synthesis or poor insulin use. This condition affects millions of individuals worldwide and is linked to a variety of consequences, including cardiovascular disease, neuropathy, nephropathy, and retinopathy. Diabetes therapy now focuses on controlling blood glucose levels through lifestyle changes, oral medicines, and insulin injections. However, these therapies have limits and may not successfully prevent or treat diabetic problems. Several marine-derived chemicals have previously demonstrated promising findings as possible antidiabetic medicines in preclinical investigations. Peptides, polyphenols, and polysaccharides extracted from seaweeds, sponges, and other marine species are among them. As a result, marine natural products have the potential to be a rich source of innovative multitargeted medications for diabetes prevention and treatment, as well as associated complications. Future research should focus on the chemical variety of marine creatures as well as the mechanisms of action of marine-derived chemicals in order to find new antidiabetic medicines and maximize their therapeutic potential. Based on preclinical investigations, this review focuses on the next step for seaweed applications as potential multitargeted medicines for diabetes, highlighting the bioactivities of seaweeds in the prevention and treatment of this illness.

First investigation into the genetic control of meiosis in sugarcane.

The sugarcane (Saccharum spp.) genome is one of the most complex of all. Modern varieties are highly polyploid and aneuploid as a result of hybridization between Saccharum officinarum and S. spontaneum. Little research has been done on meiotic control in polyploid species, with the exception of the wheat Ph1 locus harboring the ZIP4 gene (TaZIP4-B2) which promotes pairing between homologous chromosomes while suppressing crossover between homeologs. In sugarcane, despite its interspecific origin, bivalent association is favored, and multivalents, if any, are resolved at the end of prophase I. Thus, our aim herein was to investigate the purported genetic control of meiosis in the parental species and in sugarcane itself. We investigated the ZIP4 gene and immunolocalized meiotic proteins, namely synaptonemal complex proteins Zyp1 and Asy1. The sugarcane ZIP4 gene is located on chromosome 2 and expressed more abundantly in flowers, a similar profile to that found for TaZIP4-B2. ZIP4 expression is higher in S. spontaneum a neoautopolyploid, with lower expression in S. officinarum, a stable octoploid species. The sugarcane Zip4 protein contains a TPR domain, essential for scaffolding. Its 3D structure was also predicted, and it was found to be very similar to that of TaZIP4-B2, reflecting their functional relatedness. Immunolocalization of the Asy1 and Zyp1 proteins revealed that S. officinarum completes synapsis. However, in S. spontaneum and SP80-3280 (a modern variety), no nuclei with complete synapsis were observed. Importantly, our results have implications for sugarcane cytogenetics, genetic mapping, and genomics.

Impact of symbiotic insect-specific viruses on mosquito vector competence for arboviruses.

Mosquitoes are vectors for arboviruses, such as dengue, Zika, and Chikungunya. Symbiotic interactions can affect the intrinsic ability of mosquitoes to acquire and transmit arboviruses, referred to as vector competence. Insect-specific viruses (ISVs) are commonly found in symbiotic associations with mosquitoes in the wild and can affect many aspects of mosquito biology. Here, we review current knowledge on the effects of symbiotic ISV-mosquito interactions on vector competence. We discuss potential mechanisms underlying these interactions and their implications for shaping new biological control strategies. Finally, we highlight the need for field data analyzing the circulation of ISVs in mosquitoes associated with mechanistic studies in the laboratory.

The adaptor protein 2 (AP2) complex modulates habituation and behavioral selection across multiple pathways and time windows.

Animals constantly integrate sensory information with prior experience to select behavioral responses appropriate to the current situation. Genetic factors supporting this behavioral flexibility are often disrupted in neuropsychiatric conditions, such as the autism-linked ap2s1 gene which supports acoustically evoked habituation learning. ap2s1 encodes an AP2 endocytosis adaptor complex subunit, although its behavioral mechanisms and importance have been unclear. Here, we show that multiple AP2 subunits regulate acoustically evoked behavior selection and habituation learning in zebrafish. Furthermore, ap2s1 biases escape behavior choice in sensory modality-specific manners, and broadly regulates action selection across sensory contexts. We demonstrate that the AP2 complex functions acutely in the nervous system to modulate acoustically evoked habituation, suggesting several spatially and/or temporally distinct mechanisms through which AP2 regulates escape behavior selection and performance. Altogether, we show the AP2 complex coordinates action selection across diverse contexts, providing a vertebrate model for ap2s1's role in human conditions including autism spectrum disorder.

Evolutionary and functional characterization of lagomorph guanylate-binding proteins: a story of gain and loss and shedding light on expression, localization and innate immunity-related functions.

Guanylate binding proteins (GBPs) are an evolutionarily ancient family of proteins that are widely distributed among eukaryotes. They belong to the dynamin superfamily of GTPases, and their expression can be partially induced by interferons (IFNs). GBPs are involved in the cell-autonomous innate immune response against bacterial, parasitic and viral infections. Evolutionary studies have shown that GBPs exhibit a pattern of gene gain and loss events, indicative for the birth-and-death model of evolution. Most species harbor large GBP gene clusters that encode multiple paralogs. Previous functional and in-depth evolutionary studies have mainly focused on murine and human GBPs. Since rabbits are another important model system for studying human diseases, we focus here on lagomorphs to broaden our understanding of the multifunctional GBP protein family by conducting evolutionary analyses and performing a molecular and functional characterization of rabbit GBPs. We observed that lagomorphs lack GBP3, 6 and 7. Furthermore, Leporidae experienced a loss of GBP2, a unique duplication of GBP5 and a massive expansion of GBP4. Gene expression analysis by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and transcriptome data revealed that leporid GBP expression varied across tissues. Overexpressed rabbit GBPs localized either uniformly and/or discretely to the cytoplasm and/or to the nucleus. Oryctolagus cuniculus (oc)GBP5L1 and rarely ocGBP5L2 were an exception, colocalizing with the trans-Golgi network (TGN). In addition, four ocGBPs were IFN-inducible and only ocGBP5L2 inhibited furin activity. In conclusion, from an evolutionary perspective, lagomorph GBPs experienced multiple gain and loss events, and the molecular and functional characteristics of ocGBP suggest a role in innate immunity.

Three-dimensional simulation for interventional cardiology procedures: Face and content validity.

INTRODUCTION AND OBJECTIVES: Three-dimensional (3D) model simulation provides the opportunity to manipulate real devices and learn intervention skills in a realistic, controlled, and safe environment. To ensure that simulators provide a realistic surrogate to real procedures they must undergo scientific validation. We aimed to evaluate the 3D-printed simulator SimulHeart® for face and content validity to demonstrate its value as a training tool in interventional cardiology (IC). METHODS: Health professionals were recruited from sixteen Portuguese IC units. All participants received a 30-minute theoretical introduction, 10-minute demonstration of each task and then performed the intervention on a 3D-printed simulator (SimulHeart®). Finally, a post-training questionnaire focusing on the appearance of the simulation, simulation content, and satisfaction/self-efficacy was administered. RESULTS: We included 56 participants: 16 "experts" (general and interventional cardiologists), 26 "novices" (cardiology residents), and 14 nurses and allied professionals. On a five-point Likert scale, the overall mean score of face validity was 4.38±0.35 and the overall mean score of content validity was 4.69±0.32. There was no statistically significant difference in the scores provided by "experts" and "novices". Participants reported a high level of satisfaction/self-efficacy with 60.7% considering it strongly improved their skills. The majority (82.1%) "agreed" or "strongly agreed" that after the simulation they felt confident to perform the procedure on a patient. CONCLUSION: The 3D-printed simulator (SimulHeart®) showed excellent face and content validity. 3D simulation may play an important role in future IC training programs. Further research is required to correlate simulator performance with clinical performance in real patients.