A Comparison of Complication Rates between Early and Delayed Surgery among Filipino Patients with Fragility Fractures of the Hip.

Objectives: Existing standards of care recommend operative management for fragility fractures of the hip. Early intervention has been associated with lower incidence of morbidity and mortality. A lack of consensus remains in the Philippines however, regarding timing of surgery. We sought to determine the effects of surgical timing on in-hospital complications among Filipino patients with fragility hip fractures. Methods: All patients admitted for fragility hip fractures in a single tertiary-care facility from 2014-2016 were analyzed retrospectively. Subjects treated within 72 hours were grouped under "early intervention," while those managed beyond were designated "delayed intervention." Primary outcomes were complications during admission, while secondary outcome was length of hospital stay. A total of 96 patients met our inclusion criteria, of which 41 (42.71%) underwent early intervention. Baseline characteristics for both groups were comparable. Results: A significantly lower incidence of pressure ulcers (2.4% for ≤72hours vs 45.5%; p=<0.0001), pneumonia (7.32% vs 47.27%; p=<0.0001), and urinary tract infection (4.88% vs 40%; p=<0.0001), as well as shorter hospital stay (mean: 8.85 days±5.4 vs 14.6 days±13.3; p=0.01) were seen in the early intervention group. More cases of documented deep vein thrombosis were recorded in the delayed intervention group (83.3% versus 16.6%), as was the only case of in-hospital mortality. Conclusion: Early intervention showed a significantly lower incidence of in-hospital complications among patients with fragility fractures of the hip, suggesting that surgery within 72 hours may lead to better outcomes by helping to reduce the incidence of pressure sores, pneumonia, and urinary tract infection among Filipinos with hip fractures, while reducing length of admission.

Simulating adaptive grazing management on soil organic carbon in the Southeast U.S.A. using MEMS 2.

Grazing lands play a significant role in global carbon (C) dynamics, holding substantial soil organic carbon (SOC) stocks. However, historical mismanagement (e.g., overgrazing and land-use change) has led to substantial SOC losses. Regenerative practices, such as adaptive multi-paddock (AMP) grazing, offer a promising avenue to improve soil health and help combat climate change by increasing SOC accrual, both in its particulate (POC) and mineral-associated (MAOC) organic C components. Because adaptive grazing patterns emerge from the combination of different levers such as frequency, intensity, and timing of grazing, studying AMP grazing management in experimental trials and representing it in models remains challenging. Existing ecosystem models lack the capacity to predict how different adaptive grazing levers affect SOC storage and its distribution between POC and MAOC and along the soil profile accurately. Therefore, they cannot adequately assist decision-makers in effectively optimizing adaptive practices based on SOC outcomes. Here, we address this critical gap by developing version 2.34 of the MEMS 2 model. This version advances the previous by incorporating perennial grass growth and grazing submodules to simulate grass green-up and dormancy, reserve organ dynamics, the influence of standing dead plant mass on new plant growth, grass and supplemental feed consumption by animals, and their feces and urine input to soil. Using data from grazing experiments in the southeastern United States and experimental SOC data from two conventional and three AMP grazing sites in Mississippi, we tested the capacity of MEMS 2.34 to simulate grass forage production, total SOC, POC, and MAOC dynamics to 1-m depth. Further, we manipulated grazing management levers, i.e., timing, intensity, and frequency, to do a sensitivity analysis of their effects on SOC dynamics in the long term. Our findings indicate that the model can represent bahiagrass forage production (BIAS = 9.51 g C m-2, RRMSE = 0.27, RMSE = 65.57 g C m-2, R2 = 0.72) and accurately captured the dynamics of SOC fractions across sites and depths (0-15 cm: RRMSE = 0.05; 15-100 cm: RRMSE = 1.08-2.07), aligning with patterns observed in the measured data. The model best captured SOC and MAOC stocks across AMP sites in the 0-15 cm layer, while POC was best predicted at-depth. Otherwise, the model tended to overestimate SOC and MAOC below 15 cm, and POC in the topsoil. Our simulations indicate that grazing frequency and intensity were key levers for enhancing SOC stocks compared to the current management baseline, with decreasing grazing intensity yielding the highest SOC after 50 years (63.7-65.9 Mg C ha-1). By enhancing our understanding of the effects of adaptive grazing management on SOC pools in the southeastern U.S., MEMS 2.34 offers a valuable tool for researchers, producers, and policymakers to make AMP grazing management decisions based on potential SOC outcomes.

Focal pharmacological manipulation of serotonin signaling in the amygdala does not alter social behavior.

Serotonin signaling plays critical roles in social and emotional behaviors. Likewise, decades of research demonstrate that the amygdala is a prime modulator of social behavior. Permanent excitotoxic lesions and transient amygdala inactivation consistently increase social behaviors in non-human primates. In rodents, acute systemic administration of drugs that increase serotonin signaling is associated with decreased social interactions. However, in primates, the direct involvement of serotonin signaling in the amygdala, particularly in affiliative social interaction, remains unexplored. Here, we examined the effects of serotonin manipulations within the amygdala on social behavior in eight pairs of familiar male macaques. We microinfused drugs targeting the serotonin system into either the basolateral (BLA) or central (CeA) amygdala and measured changes in social behavior. Surprisingly, the results demonstrated no significant differences in social behavior following the infusion of a selective serotonin reuptake inhibitor, 5-HT1A agonist or antagonist, 5-HT2A agonist or antagonist, or 5-HT3 agonist or antagonist into either the BLA or CeA. These findings suggest that serotonin signaling in the amygdala does not directly contribute to the regulation of social behavior between familiar conspecifics. Future research should explore alternative mechanisms and potential interactions with other brain regions to gain a comprehensive understanding of the complex neural circuitry governing social behavior.

Clinical guidelines for herpes labialis: recommendations and quality evaluation according to AGREE II.

Cold sores require Healthcare professionals to employ specific approaches for prevention and management, with the need for effective therapeutic guidelines and ongoing improvement in patient care. AIM: To evalúate the methodological quality of Clinical Guidelines (CG), clinical guides and manuals for care of the population affected by herpes labialis, to verify their compliance with evidence-based health standards. MATERIALS AND METHOD: A search was conducted for CG on labial herpes in the MedicalLiteratureAnalysis andRetrieval System Online (Medline) database, Google Scholar, Brazilian Virtual Health Library (BVS), and sites of institutions/professional categories, using the descriptors "herpes labialis" or "oral herpes". Document quality was assessed using the Appraisal of Guidelines for Research & Evaluation Instrument (AGREE II). The Kappa test was used to avoid randomness or poor agreement between results. RESULTS: Analysis of the 12 selected publications on the management of labial herpes revealed flaws in quality, as the publications did not follow a quality standard. The main quality flaws identified were in "rigor in development" and "applicability. ". CONCLUSIONS: Priorities need to be redefined in the development of CG for clinical practice related to fever blisters to reduce the variability of the quality standard, and generate reliable, applicable recommendations.

A Herpes labial requer dos profissionais abordagens específicas para prevenido e manejo, com a ne-cessidade de diretrizes terapéuticas eficazes e continuo aprimoramento do cuidado ao paciente. OBJETIVO: avaliar a qualidade metodológica de documentos que abordaram Diretrizes Clínicas (DC), guias clínicos e manuais para o cuidado da populando afetada pelo herpes labial, verificando sua conformidade com padroes de saúde baseados em evidencias. MATERIAIS E MÉTODO: As DC sobre herpes labial foram pesquisadas na base de dados Medical Literature Analysis and Retrieval System Online (Medline), Google Académico, Biblioteca Virtual em Saúde (BVS) e em sites de instituigoes/categorias profissionais, utilizando os descritores "herpes labial" ou "herpes oral". Utilizamos aferramenta The Appraisal of Guidelines for Research & Evaluation Instrument (AGREE II) para a avaliagdo da qualidade. O teste Kappa também foi utilizado para evitar aleatoriedade ou baixa concordáncia entre os resultados. RESULTADOS: Na análise das 12 publicagoes selecionadas sobre o manejo do herpes labial, foram identificadas falhas na qualidade dos documentos, que ndo seguiram um padrdo de qualidade. As principais falhas de qualidade identificadas foram em "rigor no desenvolvimento" e "aplicabilida-de". CONCLUSÃO: é necessário um reenfoque para definir prioridades no desenvolvimento de DC para a prática clínica do herpes labial, a fim de reduzir a variabilidade do padrdo de qualidade e gerar recomendagoes que possam ser confiáveis e aplicáveis.

Pattern-centric transformation of omics data grounded on discriminative gene associations aids predictive tasks in TCGA while ensuring interpretability.

The increasing prevalence of omics data sources is pushing the study of regulatory mechanisms underlying complex diseases such as cancer. However, the vast quantities of molecular features produced and the inherent interplay between them lead to a level of complexity that hampers both descriptive and predictive tasks, requiring custom-built algorithms that can extract relevant information from these sources of data. We propose a transformation that moves data centered on molecules (e.g., transcripts and proteins) to a new data space focused on putative regulatory modules given by statistically relevant co-expression patterns. To this end, the proposed transformation extracts patterns from the data through biclustering and uses them to create new variables with guarantees of interpretability and discriminative power. The transformation is shown to achieve dimensionality reductions of up to 99% and increase predictive performance of various classifiers across multiple omics layers. Results suggest that omics data transformations from gene-centric to pattern-centric data supports both prediction tasks and human interpretation, notably contributing to precision medicine applications.

Investigating relationships between the host genome, rumen microbiome, and dairy cow feed efficiency using mediation analysis with structural equation modeling.

The rumen microbiome is crucial for converting feed into absorbable nutrients used for milk synthesis, and the efficiency of this process directly impacts the profitability and sustainability of the dairy industry. Recent studies have found that the rumen microbial composition explains part of the variation in feed efficiency traits, including dry matter intake, milk energy, and residual feed intake. The main goal of this study was to reveal relationships between the host genome, rumen microbiome, and dairy cow feed efficiency using structural equation models. Our specific objectives were to (i) infer the mediation effects of the rumen microbiome on feed efficiency traits, (ii) estimate the direct and total heritability of feed efficiency traits, and (iii) calculate the direct and total breeding values of feed efficiency traits. Data consisted of dry matter intake, milk energy, and residual feed intake records, SNP genotype data, and 16S rRNA rumen microbial abundances from 448 mid-lactation Holstein cows from 2 research farms. We implemented structural equation models such that the host genome directly affects the phenotype (GP → P) and the rumen microbiome (GM → P), while the microbiome affects the phenotype (M → P), partially mediating the effect of the host genome on the phenotype (G → M → P). We found that 7 to 30% of microbes within the rumen microbial community had structural coefficients different from zero. We classified these microbes into 3 groups that could have different uses in dairy farming. Microbes with heritability <0.10 but significant causal effects on feed efficiency are attractive for external interventions. On the other hand, 2 groups of microbes with heritability ≥0.10, significant causal effects, and genetic covariances and causal effects with the same or opposite sign to feed efficiency are attractive for selective breeding, improving or decreasing the trait heritability and response to selection, respectively. In general, the inclusion of the different microbes in genomic models tends to decrease the trait heritability rather than increase it, ranging from -15% to +5%, depending on the microbial group and phenotypic trait. Our findings provide more understanding to target rumen microbes that can be manipulated, either through selection or management interventions, to improve feed efficiency traits.

TRPV4-Expressing Tissue-Resident Macrophages Regulate the Function of Collecting Lymphatic Vessels via Thromboxane A2 Receptors in Lymphatic Muscle Cells.

Rationale: TRPV4 channels are critical regulators of blood vascular function and have been shown to be dysregulated in many disease conditions in association with inflammation and tissue fibrosis. These are key features in the pathophysiology of lymphatic system diseases, including lymphedema and lipedema; however, the role of TRPV4 channels in the lymphatic system remains largely unexplored. TRPV4 channels are calcium permeable, non-selective cation channels that are activated by diverse stimuli, including shear stress, stretch, temperature, and cell metabolites, which may regulate lymphatic contractile function. Objective: To characterize the expression of TRPV4 channels in collecting lymphatic vessels and to determine the extent to which these channels regulate the contractile function of lymphatics. Methods and Results: Pressure myography on intact, isolated, and cannulated lymphatic vessels showed that pharmacological activation of TRPV4 channels with GSK1016790A (GSK101) led to contractile dysregulation. The response to GSK101 was multiphasic and included, 1) initial robust constriction that was sustained for ≥1 minute and in some instances remained for ≥4 minutes; and 2) subsequent vasodilation and partial or complete inhibition of lymphatic contractions associated with release of nitric oxide. The functional response to activation of TRPV4 channels displayed differences across lymphatics from four anatomical regions, but these differences were consistent across different species (mouse, rat, and non-human primate). Importantly, similar responses were observed following activation of TRPV4 channels in arterioles. The initial and sustained constriction was prevented with the COX inhibitor, indomethacin. We generated a controlled and spatially defined single-cell RNA sequencing (scRNAseq) dataset from intact and microdissected collecting lymphatic vessels. Our data uncovered a subset of macrophages displaying the highest expression of Trpv4 compared to other cell types within and surrounding the lymphatic vessel wall. These macrophages displayed a transcriptomic profile consistent with that of tissue-resident macrophages (TRMs), including differential expression of Lyve1 , Cd163 , Folr2 , Mrc1 , Ccl8 , Apoe , Cd209f , Cd209d , and Cd209g ; and at least half of these macrophages also expressed Timd4. This subset of macrophages also highly expressed Txa2s , which encodes the thromboxane A2 (TXA2) synthase. Inhibition of TXA2 receptors (TXA2Rs) prevented TRPV4-mediated contractile dysregulation. TXA2R activation on LMCs caused an increase in mobilization of calcium from intracellular stores through Ip3 receptors which promoted store operated calcium entry and vasoconstriction. Conclusions: Clinical studies have linked cancer-related lymphedema with an increased infiltration of macrophages. While these macrophages have known anti-inflammatory and pro-lymphangiogenic roles, as well as promote tissue repair, our results point to detrimental effects to the pumping capacity of collecting lymphatic vessels mediated by activation of TRPV4 channels in macrophages. Pharmacological targeting of TRPV4 channels in LYVE1-expressing macrophages or pharmacological targeting of TXA2Rs may offer novel therapeutic strategies to improve lymphatic pumping function and lymph transport in lymphedema.

PARROT BORNAVIRUSES IN PSITTACINES KEPT IN CAPTIVITY IN THE STATE OF SANTA CATARINA, BRAZIL.

Parrot bornaviruses are responsible for proventricular dilatation disease (PDD) in psittacines. This study aimed to determine the occurrence and factors associated with Parrot bornaviruses infection in psittacines kept in captivity in a state in the southern region of Brazil. A cross-sectional study was carried out with 192 birds from two facilities (A and B) in 2019, using choanal, esophageal, and cloacal swabs and feathers, totaling 768 samples subjected to reverse-transcription polymerase chain reaction (RT-PCR), for the matrix (M) protein gene with a final product of 350 base pairs (bp). Genetic sequencing of three positive samples was performed by the Sanger method. In the study, the overall virus occurrence was 35.9% (69/192), with 40.4% (42/104) in Facility A and 30.7% (27/88) in Facility B. Sequencing analysis of the samples revealed the presence of Parrot bornavirus 2 (PaBV-2) in both facilities. Swab samples from the choanal (40/69), esophageal (30/69), cloacal (35/69), and feather (15/69) tested positive, facilitating the molecular diagnosis of Parrot bornaviruses. The results indicated that there is no single ideal sample type for antemortem molecular diagnosis of this virus. Simultaneously testing all four samples at the same time point yielded more diagnoses than testing any single sample among the four. Most of the 29 sampled psittacine species were native, and 46.9% of the birds (90/192) consisted of endangered species. Among the psittacines that tested positive, 88.4% (61/69) were clinically healthy, and 8.7% (6/69) exhibited clinical or behavioral signs, including behavioral changes, alterations in feathering, and changes in body score at the time of collection. This study showcases the application of minimally invasive sampling for diagnosing Parrot bornaviruses, enabling sample collection when the birds are restrained for clinical evaluation. This approach facilitates a prompt and effective antemortem diagnosis, thereby serving as an efficient screening method for parrots kept in captivity.

Additive Manufacturing Titanium Dental Implants Placed in Sinuses Grafted with 70HA:30-TCP: A One-Year Retrospective Study for Evaluation of Survival Rate.

The present short-term retrospective study evaluated the implant survival rate and peri-implant bone loss around additive-manufactured titanium implants placed in sinuses grafted with Plenum Osshp (Plenum Bioengenharia, Jundia, SP, Brazil) (70HA:30ß-TCP) material. A total of 39 implants were inserted after 23 sinus floor elevation procedures in 16 consecutive patients. Prosthetic rehabilitation included fixed partial prostheses (three units), single crowns (eleven units), and fixed full arches (three units). Clinical and radiographic parameters of implant-supported restorations were evaluated after at least one year of occlusal loading. The implant-crown success criteria included the absence of pain, suppuration, and clinical mobility, an average distance between the implant shoulder and the first visible bone contact (DIB) < 1.0 mm from the initial surgery, and the absence of prosthetic complications at the implant-abutment interface. The overall cumulative implant survival rate was 97.43%. No prosthetic complications at the implant-abutment interface were reported. After one year, the mean DIB was 0.23 mm ± 0.14. Within the limits of this retrospective study, it can be concluded that 70 HA:30 ß-TCP allowed stable and reliable bone support to maintain healthy conditions around titanium dental implants produced by additive manufacturing.

Digest: When sexual selection hits the wall of natural selection.

Sexual selection often drives traits in a direction that is disfavored by natural selection. The balance between these two types of selection can shift rapidly in response to environmental changes. Gallagher et al. (2024) report such a shift in the cricket population following the introduction of a parasitoid fly. The ancestral male morph, though still preferred by females, has been supplanted by multiple novel morphs that are more difficult for the parasitoid to detect.

Pulmonary embolism versus pulmonary vasculitis in Hughes-Stovin syndrome: Characteristic computed tomography pulmonary angiographic findings and diagnostic and therapeutic implications. HSS International Study Group.

BACKGROUND AND AIM: Hughes-Stovin syndrome (HSS) is a rare systemic vasculitis with widespread venous/arterial thrombosis and pulmonary vasculitis. Distinguishing between pulmonary embolism (PE) and in-situ thrombosis in the early stages of HSS is challenging. The aim of the study is to compare clinical, laboratory, and computed tomography pulmonary angiography (CTPA) characteristics in patients diagnosed with PE versus those with HSS. METHODS: This retrospective study included 40 HSS patients with complete CTPA studies available, previously published by the HSS study group, and 50 patients diagnosed with PE from a single center. Demographics, clinical and laboratory findings, vascular thrombotic events, were compared between both groups. The CTPA findings were reviewed, with emphasis on the distribution, adherence to the mural wall, pulmonary infarction, ground glass opacification, and intra-alveolar hemorrhage. Pulmonary artery aneurysms (PAAs) in HSS were assessed and classified. RESULTS: The mean age of HSS patients was 35 ± 12.3 years, in PE 58.4 ± 17 (p < 0.0001). Among PE 39(78 %) had co-morbidities, among HSS none. In contrast to PE, in HSS both major venous and arterial thrombotic events are seen.. Various patterns of PAAs were observed in the HSS group, which were entirely absent in PE. Parenchymal hemorrhage was also more frequent in HSS compared to PE (P < 0.001). CONCLUSION: Major vascular thrombosis with arterial aneurysms formation are characteristic of HSS. PE typically appear loosely-adherent and mobile whereas "in-situ thrombosis" seen in HSS is tightly-adherent to the mural wall. Mural wall enhancement and PAAs are distinctive pulmonary findings in HSS. The latter findings have significant therapeutic ramifications.

TREM2 deficiency reprograms intestinal macrophages and microbiota to enhance anti-PD-1 tumor immunotherapy.

The gut microbiota and tumor-associated macrophages (TAMs) affect tumor responses to anti-programmed cell death protein 1 (PD-1) immune checkpoint blockade. Reprogramming TAM by either blocking or deleting the macrophage receptor triggering receptor on myeloid cells 2 (TREM2) attenuates tumor growth, and lack of functional TREM2 enhances tumor elimination by anti-PD-1. Here, we found that anti-PD-1 treatment combined with TREM2 deficiency in mice induces proinflammatory programs in intestinal macrophages and a concomitant expansion of Ruminococcus gnavus in the gut microbiota. Gavage of wild-type mice with R. gnavus enhanced anti-PD-1-mediated tumor elimination, recapitulating the effect occurring in the absence of TREM2. A proinflammatory intestinal environment coincided with expansion, increased circulation, and migration of TNF-producing CD4+ T cells to the tumor bed. Thus, TREM2 remotely controls anti-PD-1 immune checkpoint blockade through modulation of the intestinal immune environment and microbiota, with R. gnavus emerging as a potential probiotic agent for increasing responsiveness to anti-PD-1.

Shifts in uterine microbiome associated with pregnancy outcomes at first insemination and clinical cure in dairy cows with metritis.

Objectives were to assess differences in uterine microbiome associated with clinical cure and pregnancy outcomes in dairy cows treated for metritis. Cows with metritis (reddish-brownish, watery, and fetid vaginal discharge) were paired with cows without metritis based on parity and days postpartum. Uterine contents were collected through transcervical lavage at diagnosis, five days later following antimicrobial therapy (day 5), and at 40 days postpartum. Uterine microbiome was assessed by sequencing the V4 hypervariable region of the 16S rRNA gene. Although alpha-diversity based on Chao1, Shannon, and inverse Simpson indexes at diagnosis did not differ between cows with and without metritis, disease was associated with differences in beta-diversity. Prevalence of Porphyromonas, Bacteroides, and Veillonella was greater in cows with metritis. Streptococcus, Sphingomonas, and Ureaplasma were more prevalent in cows without metritis. Differences in beta-diversity between cows with and without metritis persisted on day 5. Uterine microbiome was not associated with clinical cure. Richness and alpha-diversity, but not beta-diversity, of uterine microbiome 40 days postpartum were associated with metritis and pregnancy. No relationship between uterine microbiome and pregnancy outcomes was observed. Results indicate that factors other than changes in intrauterine bacterial community underlie fertility loss and clinical cure in cows with metritis.

Pamrevlumab for Idiopathic Pulmonary Fibrosis: The ZEPHYRUS-1 Randomized Clinical Trial.

Importance: Current treatments for idiopathic pulmonary fibrosis slow the rate of lung function decline, but may be associated with adverse events that affect medication adherence. In phase 2 trials, pamrevlumab (a fully human monoclonal antibody that binds to and inhibits connective tissue growth factor activity) attenuated the progression of idiopathic pulmonary fibrosis without substantial adverse events. Objective: To assess the efficacy and safety of pamrevlumab for patients with idiopathic pulmonary fibrosis. Design, Setting, and Participants: Phase 3 randomized clinical trial including 356 patients aged 40 to 85 years with idiopathic pulmonary fibrosis who were not receiving antifibrotic treatment with nintedanib or pirfenidone at enrollment. Patients were recruited from 117 sites in 9 countries between July 18, 2019, and July 29, 2022; the last follow-up encounter occurred on August 28, 2023. Interventions: Pamrevlumab (30 mg/kg administered intravenously every 3 weeks; n = 181) or placebo (n = 175) for 48 weeks. Main Outcomes and Measures: The primary outcome was absolute change in forced vital capacity (FVC) from baseline to week 48. There were 5 secondary outcomes (including time to disease progression, which was defined as a decline of ≥10% in predicted FVC or death). The exploratory outcomes included patient-reported symptoms. Adverse events were reported. Results: Among 356 patients (mean age, 70.5 years; 258 [72.5%] were men; 221 [62.1%] were White), 277 (77.8%) completed the trial. There was no significant between-group difference for absolute change in FVC from baseline to week 48 (least-squares mean, -260 mL [95% CI, -350 to -170 mL] in the pamrevlumab group vs -330 mL [95% CI, -430 to -230 mL] in the placebo group; mean between-group difference, 70 mL [95% CI, -60 to 190 mL], P = .29). There were no significant between-group differences in any of the secondary outcomes or in the patient-reported outcomes. In the pamrevlumab group, there were 160 patients (88.4%) with treatment-related adverse events and 51 patients (28.2%) with serious adverse events vs 151 (86.3%) and 60 (34.3%), respectively, in the placebo group. During the study, 23 patients died in each group (12.7% in the pamrevlumab group vs 13.1% in the placebo group). Conclusions and Relevance: Among patients with idiopathic pulmonary fibrosis treated with pamrevlumab or placebo, there was no statistically significant between-group difference for the primary outcome of absolute change in FVC from baseline to week 48. Trial Registration: ClinicalTrials.gov Identifier: NCT03955146.

Characterizing unstructured data with the nearest neighbor permutation entropy.

Permutation entropy and its associated frameworks are remarkable examples of physics-inspired techniques adept at processing complex and extensive datasets. Despite substantial progress in developing and applying these tools, their use has been predominantly limited to structured datasets such as time series or images. Here, we introduce the k-nearest neighbor permutation entropy, an innovative extension of the permutation entropy tailored for unstructured data, irrespective of their spatial or temporal configuration and dimensionality. Our approach builds upon nearest neighbor graphs to establish neighborhood relations and uses random walks to extract ordinal patterns and their distribution, thereby defining the k-nearest neighbor permutation entropy. This tool not only adeptly identifies variations in patterns of unstructured data but also does so with a precision that significantly surpasses conventional measures such as spatial autocorrelation. Additionally, it provides a natural approach for incorporating amplitude information and time gaps when analyzing time series or images, thus significantly enhancing its noise resilience and predictive capabilities compared to the usual permutation entropy. Our research substantially expands the applicability of ordinal methods to more general data types, opening promising research avenues for extending the permutation entropy toolkit for unstructured data.

Pharmacological Inhibition of the Nucleus Accumbens Increases Dyadic Social Interaction in Macaques.

The nucleus accumbens (NAc) is a central component of the brain circuitry that mediates motivated behavior, including reward processing. Since the rewarding properties of social stimuli have a vital role in guiding behavior (both in humans and nonhuman animals), the NAc is likely to contribute to the brain circuitry controlling social behavior. In rodents, prior studies have found that focal pharmacological inhibition of NAc and/or elevation of dopamine in NAc increases social interactions. However, the role of the NAc in social behavior in nonhuman primates remains unknown. We measured the social behavior of eight dyads of male macaques following (1) pharmacological inhibition of the NAc using the GABAA agonist muscimol and (2) focal application of quinpirole, an agonist at the D2 family of dopamine receptors. Transient inhibition of the NAc with muscimol increased social behavior when drug was infused in submissive, but not dominant partners of the dyad. Focal application of quinpirole was without effect on social behavior when infused into the NAc of either dominant or submissive subjects. Our data demonstrate that the NAc contributes to social interactions in nonhuman primates.

Growth and carbon turnover of Piaractus mesopotamicus Holmberg, 1887 (Osteicthyes: Characidae): contribution of extruded feed and natural food.

Piaractus mesopotamicus, is a fish usually farmed in semi-intensive systems with access to natural food and supplementary feed. This study evaluates effects of feed allowance on the productive performance, carbon turnover and proportions of nutrient (carbon) contribution of feed and natural food for the growth of pacu. Juvenile fish were stocked in fiberglass tanks and fed to 100, 75, 50, 25, 0% apparent satiety (ApS), with a practical, extruded (C4 photosynthetic pathway) feed in a randomized design trial (n=3); plankton production for simulated semi-intensive farming system condition was induced by chemical fertilization. A control treatment was set up in tanks devoid of natural food. Data on muscle stable carbon isotope ratios were used to study carbon turnover using a relative growth-based model. Low variation of the δ13C impaired fitting a turnover model curve for the 0 and 25 % ApS treatments. Fish of the 100% and 75% ApS treatments reached circa 95% and 82.85% of the carbon turnover, respectively. Extruded feed was the main nutrient source for the growth of pacu in the semi-intensive, simulated farming condition. The current study contributes to the knowledge of the relationship between feeding rates and carbon turnover rates in the pacu muscle.

The Cloning and Characterization of a Three-Finger Toxin Homolog (NXH8) from the Coralsnake Micrurus corallinus That Interacts with Skeletal Muscle Nicotinic Acetylcholine Receptors.

Coralsnakes (Micrurus spp.) are the only elapids found throughout the Americas. They are recognized for their highly neurotoxic venom, which is comprised of a wide variety of toxins, including the stable, low-mass toxins known as three-finger toxins (3FTx). Due to difficulties in venom extraction and availability, research on coralsnake venoms is still very limited when compared to that of other Elapidae snakes like cobras, kraits, and mambas. In this study, two previously described 3FTx from the venom of M. corallinus, NXH1 (3SOC1_MICCO), and NXH8 (3NO48_MICCO) were characterized. Using in silico, in vitro, and ex vivo experiments, the biological activities of these toxins were predicted and evaluated. The results showed that only NXH8 was capable of binding to skeletal muscle cells and modulating the activity of nAChRs in nerve-diaphragm preparations. These effects were antagonized by anti-rNXH8 or antielapidic sera. Sequence analysis revealed that the NXH1 toxin possesses eight cysteine residues and four disulfide bonds, while the NXH8 toxin has a primary structure similar to that of non-conventional 3FTx, with an additional disulfide bond on the first loop. These findings add more information related to the structural diversity present within the 3FTx class, while expanding our understanding of the mechanisms of the toxicity of this coralsnake venom and opening new perspectives for developing more effective therapeutic interventions.