Brain Charts for the Rhesus Macaque Lifespan.

Recent efforts to chart human brain growth across the lifespan using large-scale MRI data have provided reference standards for human brain development. However, similar models for nonhuman primate (NHP) growth are lacking. The rhesus macaque, a widely used NHP in translational neuroscience due to its similarities in brain anatomy, phylogenetics, cognitive, and social behaviors to humans, serves as an ideal NHP model. This study aimed to create normative growth charts for brain structure across the macaque lifespan, enhancing our understanding of neurodevelopment and aging, and facilitating cross-species translational research. Leveraging data from the PRIMatE Data Exchange (PRIME-DE) and other sources, we aggregated 1,522 MRI scans from 1,024 rhesus macaques. We mapped non-linear developmental trajectories for global and regional brain structural changes in volume, cortical thickness, and surface area over the lifespan. Our findings provided normative charts with centile scores for macaque brain structures and revealed key developmental milestones from prenatal stages to aging, highlighting both species-specific and comparable brain maturation patterns between macaques and humans. The charts offer a valuable resource for future NHP studies, particularly those with small sample sizes. Furthermore, the interactive open resource (https://interspeciesmap.childmind.org) supports cross-species comparisons to advance translational neuroscience research.

"More Areas of Grey": Ambiguities in Neuropalliative Care.

Neuropalliative care as a clinical speciality aims to address the unique end-of-life needs and concerns of patients with neurologic disease. Although literature has outlined clinical hurdles, a more nuanced understanding of how neuropalliative care was experienced, conceptualized, and enacted could provide context and depth to better outline practice and research priorities. This article presents findings from an ethnographic study of neuropalliative care conducted in a university-affiliated, tertiary care neurological hospital in Canada with a dedicated neuropalliative consultation service. Specifically, this article examines how clinical hurdles outlined in the neuropalliative literature were experienced and addressed by multiple stakeholders, including patients, families, and clinicians. These clinical hurdles include locating the scope of neuropalliative care, ascertaining the impact of prognostic uncertainty and poor recognition of the dying patient, and navigating the tensions between curative and palliative philosophies. In the discussion, the implications of these clinical hurdles are addressed, concluding with reflections on the role of ethnography, palliative care in the context of functional changes, and broadening approaches to uncertainty.

Antileishmanial activity of a dillapiole derivative obtained from Piper aduncum L. (Piperaceae).

Cutaneous leishmaniasis (CL) is considered a public health problem. Current treatments have disadvantages because they are invasive and have serious side effects, and thus there is a need for research into new, more effective pharmacological alternatives. Plants are promising sources of bioactive substances, and new analogues can be obtained through chemical reactions. The present study aimed to evaluate the antileishmanial effects of the analog dillapiole n-butyl ether (DBE) extracted from Piper aduncum leaves. The cytotoxic potential of DBE was evaluated at concentrations of 15.62 to 500 µM in peritoneal macrophages for 48 h, and in RAW 264.7 macrophages for 72 h using a dose-response method. The antileishmanial activity in L. amazonensis promastigotes used concentrations of 0.2 to 4.5 µM for 24, 48 and 72 h and the quantification of the cellular infection rate used a concentration of 4.5 µM of DBE against the amastigote forms internalized in macrophages for 24 h and 48 h. Nitric oxide was quantified from macrophages previously treated with DBE for 24 h and 48 h. The dosage of reactive oxygen species used a concentration of 4.5 µM of DBE incubated together with dichlorofluorescein acetate for 1, 3, 6, and 24 h. For the molecular modeling of DBE, the Leishmania protein, available in the "Protein Data Bank" database, was used. The studied molecule was not toxic to cells and presented a CC50 of 413 µM in peritoneal macrophages and 373.5 µM in RAW 264.7. The analogue inhibited promastigote forms of L. amazonensis with an IC50 of 1.6 µM for 72 h. DBE presented an infection rate of 17% and 12%, dillapiole of 24% and 14% and Pentacarinat® of 10% and 9% over 48 h. DBE demonstrated a binding energy of -7.8 for the U53 enzyme. It is concluded that the analogue showed promising antileishmanial activity for future in vivo tests.

NPCC4: Tail risk, climate drivers of extreme heat, and new methods for extreme event projections.

We summarize historic New York City (NYC) climate change trends and provide the latest scientific analyses on projected future changes based on a range of global greenhouse gas emissions scenarios. Building on previous NPCC assessment reports, we describe new methods used to develop the projections of record for sea level rise, temperature, and precipitation for NYC, across multiple emissions pathways and analyze the issue of the "hot models" associated with the 6th phase of the Coupled Model Intercomparison Project (CMIP6) and their potential impact on NYC's climate projections. We describe the state of the science on temperature variability within NYC and explain both the large-scale and regional dynamics that lead to extreme heat events, as well as the local physical drivers that lead to inequitable distributions of exposure to extreme heat. We identify three areas of tail risk and potential for its mischaracterization, including the physical processes of extreme events and the effects of a changing climate. Finally, we review opportunities for future research, with a focus on the hot model problem and the intersection of spatial resolution of projections with gaps in knowledge in the impacts of the climate signal on intraurban heat and heat exposure.

NPCC4: Climate change and New York City's flood risk.

This chapter of the New York City Panel on Climate Change 4 (NPCC4) report provides a comprehensive description of the different types of flood hazards (pluvial, fluvial, coastal, groundwater, and compound) facing New York City and provides climatological context that can be utilized, along with climate change projections, to support flood risk management (FRM). Previous NPCC reports documented coastal flood hazards and presented trends in historical and future precipitation and sea level but did not comprehensively assess all the city's flood hazards. Previous NPCC reports also discussed the implications of floods on infrastructure and the city's residents but did not review the impacts of flooding on the city's natural and nature-based systems (NNBSs). This-the NPCC's first report focused on all drivers of flooding-describes and profiles historical examples of each type of flood and summarizes previous and ongoing research regarding exposure, vulnerability, and risk management, including with NNBS and nonstructural measures.

Morphological dental age estimation of adults using the radiographic canine pulp/tooth area ratio.

The reduction of the pulpal space following the deposition of secondary dentin is a radiographically visible morphological feature associated with aging. Currently, there is no reference morphological sample for the Northern Brazilian population when it comes to the radiographically visible dental features for age estimation. This study aimed to test an existing method for age estimation based on the canine pulp/tooth area (PTA) ratio and develop a population-specific equation. The sample consisted of 100 peri-apical radiographs of Brazilian males (n=46) and females (n=54) from the Northern geographic region. The age of the sampled participants was between 18 and 72 years (mean age=45.43±14.39years). The estimated age was obtained with the Cameriere's method. A statistically significant negative (r=-0.595) association was observed between the permanent canine PTA and the chronological age (P=0.0001). A population-specific equation was structured with a 4-fold (75%×25%) cross-validation, leading to a mean absolute error of 9.59years, and root mean square error of 11.66years (r2=0.363). This study provided evidence to support the use of Cameriere's pulp/tooth area ratio for the radiographic dental age estimation of Northern Brazilian adults, especially adjusted with a population-specific equation.

Basic action protocol for the outpatient management of chronic heart failure of the Spanish society of internal medicine.

Chronic heart failure (CHF) represents a challenge for the healthy system due to its high prevalence, high burden of morbidity and mortality, and high consumption of health resources. To address this problem, it is necessary to develop efficient management strategies that include both hospital care and outpatient care. The primary objective is to stabilize the patient and prevent decompensation, with the consequent improvement in quality of life, reduction in hospital admissions and emergency department care, and, consequently, reduction in healthcare costs. In this context, the heart failure and atrial fibrilation working group of the Spanish Society of Internal Medicine has developed a protocol for the management of outpatient CHF, that addresses, from the perspective of Internal medicine, all the problems suffered by the patient with CHF. This protocol aims to optimize pharmacological treatment, control cardiovascular risk factors and various comorbidities, educate the patient and their environment about the disease, promote adherence to treatment and stablish follow-up adapted to their condition.

Investigating the potential of pyrazine dioxide based-compounds as organic electrodes for batteries.

Understanding structure-property relationship in redox-active molecular species is of central importance in various fields, including many medicinal and chemical applications. The quest for performant organic electrodes in the context of energy storage calls for pioneering studies to develop new and possibly optimal materials. Beyond modifying the molecular design of the existing compounds through functionalization, expansion of the search enabling the advent of efficient new backbones can potentially lead to breakthroughs in this research area. The number of already identified families able to constitute negative organic electrodes is much lower than that of their positive counterparts, which calls for finding ways to bridge this gap. To expand the dataset of known predicted redox potentials and in view of reaching an educated guess about the abilities of some eventual new redox active electrodes, we examined the properties of pyrazine N,N'-dioxide (PZDO) and its fully methylated functionalized derivative (TeMePzDO). The aspects and mechanisms driving the various features characteristic of these compounds were unraveled through molecular and periodic DFT calculations combined with accurate electronic structure analysis. The predicted molecular redox/crystalline intercalation potentials lead to the classification of PZDO and TeMePzDO systems within the class of negative electrodes, with features that are significantly appealing compared to those of some existing systems with backbones suited for such kind of application.

Double Internal Hernia: Laparoscopic Resolution.

Gastric bypass surgery is a common and effective procedure for obesity and associated comorbidities. However, long-term complications, such as internal hernias, can pose diagnostic and therapeutic challenges. Internal hernias after gastric bypass are rare but can lead to severe complications, including volvulus and bowel ischemia. Understanding the anatomical variations and employing laparoscopic techniques for resolution are crucial in managing these cases.

"We are not the person we will be when these things happen:" Reflections on personhood from an ethnography of neuropalliative care.

Neuropalliative care developed to address the needs of patients living with life-limiting neurologic disease. One critical consideration is that disease-related changes to cognition, communication, and function challenge illness experiences and care practices. We conducted an ethnography to understand neuropalliative care as a phenomenon; how it was experienced, provided, conceptualized. Personhood served as our conceptual framework; with its long philosophical history and important place in nursing theory, we examined the extent to which it captured neuropalliative experiences and concerns. Personhood contextualized complex losses, aligning the impact of functional and relational changes. Cognition, communication, and functional alterations stretched conceptions of personhood, insinuating it can be relational, fluid, adaptive. Although normative conceptions of personhood guided research and decision-making, ethical considerations suggested personhood could be transformed, remade. We consider the implications of our findings through three themes. First, we examine how literature on illness experience fails to integrate the realities of people living with and dying from neurologic disease; we counter this by interrogating the concept of experience. Second, we turn to Ricoeur's work on recognition to illuminate relational conceptions of personhood to inform care practices. Finally, we reflect on how personhood can bridge the gap left by functional changes, enhance relational engagement, and promote dignity at the end of life.

Machine learning assisted 5-part tooth segmentation method for CBCT-based dental age estimation in adults.

BACKGROUND: The utilization of segmentation method using volumetric data in adults dental age estimation (DAE) from cone-beam computed tomography (CBCT) was further expanded by using current 5-Part Tooth Segmentation (SG) method. Additionally, supervised machine learning modelling -namely support vector regression (SVR) with linear and polynomial kernel, and regression tree - was tested and compared with the multiple linear regression model. MATERIAL AND METHODS: CBCT scans from 99 patients aged between 20 to 59.99 was collected. Eighty eligible teeth including maxillary canine, lateral incisor, and central incisor were used in this study. Enamel to dentine volume ratio, pulp to dentine volume ratio, lower tooth volume ratio, and sex was utilized as independent variable to predict chronological age. RESULTS: No multicollinearity was detected in the models. The best performing model comes from maxillary lateral incisor using SVR with polynomial kernel ( = 0.73). The lowest error rate achieved by the model was given also by maxillary lateral incisor, with 4.86 years of mean average error and 6.05 years of root means squared error. However, demands a complex approach to segment the enamel volume in the crown section and a lengthier labour time of 45 minutes per tooth.

Enhancing children's participation in dental research: A commentary.

The concept of childhood has evolved over the years, inspired by the United Nations Convention on the Rights of the Child in 1989, shifting from developmental models to a conception of childhood that recognizes children as moral agents. This evolution highlights the importance of respecting children's agency and their right to be heard in matters that are related to them. In conventional health research, however, children's voices are often inadequately accessed. In this commentary, we discuss the imperative to recognize children's agency in dental research and a shift from research on children to research with and by children. Moreover, we underscore the importance of actively seeking and listening to children's voices and recognizing their agency in shaping research and healthcare practices in the field of dentistry. Further, we explore the application of participatory research approaches in dental research and provide examples of studies that have involved children in various capacities. We conclude this commentary by emphasizing the potential benefits of participatory research in both qualitative and quantitative dental studies to promote deeper understanding, clearer communication, and stronger advocacy regarding children's interests. Primarily, we call for greater recognition of children's agency in dental research and advocate for more inclusive and child-centred research methodologies.

Nadir prostate-specific antigen after salvage cryotherapy as a potential prognostic factor for oncologic outcomes.

PURPOSE: To report oncologic outcomes of patients undergoing salvage cryotherapy (SCT) for local recurrence of prostate cancer (PCa) and to establish a nadir PSA (nPSA) value that best defines long-term oncologic success. METHODS: Retrospective study of men who underwent SCT for local recurrence of PCa between 2008 and 2020. SCT was performed in men with biochemical recurrence (BCR), after primary treatment and with biopsy-proven PCa local recurrence. Survival analysis with Kaplan-Meier and Cox models was performed. We determined the optimal cutoff nPSA value after SCT that best classifies patients depending on prognosis. RESULTS: Seventy-seven men who underwent SCT were included. Survival analysis showed a 5-year biochemical recurrence-free survival (BRFS), androgen deprivation therapy-free survival (AFS), and metastasis-free survival (MFS) after SCT of 48.4%, 62% and 81.3% respectively. On multivariable analysis for perioperative variables associated with BCR, initial ISUP, pre-SCT PSA, pre-SCT prostate volume and post-SCT nPSA emerged as variables associated with BCR. The cutoff analysis revealed an nPSA < 0.5 ng/ml to be the optimal threshold that best defines success after SCT. 5-year BRFS for patients achieving an nPSA < 0.5 vs nPSA ≥ 0.5 was 64% and 9.5% respectively (p < 0.001). 5-year AFS for men with nPSA < 0.5 vs ≥ 0.5 was 81.2% and 12.2% (p < 0.001). Improved 5-year MFS for patients who achieved nPSA < 0.5 was also obtained (89.6% vs 60%, p = 0.003). CONCLUSION: SCT is a feasible rescue alternative for the local recurrence of PCa. Achieving an nPSA < 0.5 ng/ml after SCT is associated with higher long-term BRFS, AFS and MFS rates.

Development and growth of bovine calves demi-embryos.

The aim of this study was to investigate the growth and development of animals produced from demi-embryos and compare them with whole embryos from fetus to adult life. To achieve this, calves produced from fresh demi-embryos and whole embryos were individually transferred and monitored from 60 days of pregnancy until slaughter at 550 days. Ultrasound scans were conducted on fetuses at 60 and 90 days to evaluate the biparietal, abdominal, umbilical cord, orbital, and aorta diameters. Subsequently, morphological traits of newborn calves were measured at 0, 7, and 21 days (N = 18). Live weight was recorded at birth, weaning, and every 30 days thereafter until slaughter at 550 days. The growth curve of each group was modeled using logistic regression, and the factors of the respective functions were compared. As early as 60 days of pregnancy, ultrasound evaluations revealed no morphometric differences between fetuses produced from demi-embryos and those from whole embryos. This lack of differentiation persisted in the morphometric evaluations of newborns up to 21 days of age, as well as in live weight and the growth curve from birth to slaughter. Moreover, there were no significant differences between the groups in terms of rib eye area and fat thickness evolution. Consequently, individuals from demi-embryos exhibited no discernible disparities to those whole embryos in growth and development from 60 days of gestation, through birth, and into adulthood.

Radiographic morphology of canines tested for sexual dimorphism via convolutional-neural-network-based artificial intelligence.

The permanent left mandibular canines have been used for sexual dimorphism when human identification is necessary. Controversy remains whether the morphology of these teeth is actually useful to distinguish males and females. This study aimed to assess the sexual dimorphism of canines by means of a pioneering artificial intelligence approach to this end. A sample of 13,046 teeth radiographically registered from 5838 males and 7208 females between the ages of 6 and 22.99 years was collected. The images were annotated using Darwin V7 software. DenseNet121 was used and tested based on binary answers regarding the sex (male or female) of the individuals for 17 age categories of one year each (i.e. 6-6.99, 7.7.99… 22.22.99). Accuracy rates, receiver operating characteristic (ROC) curves and confusion matrices were used to quantify and express the artificial intelligence's classification performance. The accuracy rates across age categories were between 57-76% (mean: 68%±5%). The area under the curve (AUC) of the ROC analysis was between 0.58 and 0.77. The best performances were observed around the age of 12 years, while the worst were around the age of 7 years. The morphological analysis of canines for sex estimation should be restricted and allowed in practice only when other sources of dimorphic anatomic features are not available.

Preeclampsia pravastatin early VS late treatment: Effects on oxidative stress and vascular reactivity.

Early diagnosis and efficient treatment of preeclampsia remains a medical challenge and etiological factors converge in a deficient placentation that triggers oxidative stress. There is evidence that statins show antioxidant effects that can improve endothelial function without adverse perinatal effects. We aimed to compare early vs. late pravastatin treatment on the oxidative stress and cardiovascular features of an experimental model of preeclampsia. Female Wistar rats were randomly divided into preeclampsia phenotype rats (PEP) developed by sub renal aortic coarctation (SRAC) and healthy pregnant rats (C). Each group received pravastatin (5 mg/Kg) p.o. either for one week before and during the first week or during the last two weeks of gestation. Blood pressure was determined using the plethysmographic method. Phenylephrine (Phe)-induced contractility was evaluated in isolated thoracic and abdominal aortic rings with or without endothelium. Blood samples were obtained to determine anion superoxide concentration as indicator of NADPH activity. Two-way ANOVA and Bonferroni post hoc tests were used to define statistical significance. Early or late pravastatin treatment decreased hypertension of PEP animals but did not change BP of the healthy pregnant group. Thoracic and abdominal aorta from PEP rats showed increased contractility that was reverted by pravastatin early treatment in endothelium intact rings. Pravastatin did not significantly change contractility neither in the thoracic nor in the abdominal aorta segments from healthy pregnant control rats (C), and decrease anion superoxide concentration by NADPH activity. We conclude pravastatin can improve both blood pressure and endothelium-dependent Phe-induced contractility in an experimental model of preeclampsia by reducing oxidative stress.

Applying artificial intelligence to determination of legal age of majority from radiographic data.

Forensic odontologists use biological patterns to estimate chronological age for the judicial system. The age of majority is a legally significant period with a limited set of reliable oral landmarks. Currently, experts rely on the questionable development of third molars to assess whether litigants can be prosecuted as legal adults. Identification of new and novel patterns may illuminate features more dependably indicative of chronological age, which have, until now, remained unseen. Unfortunately, biased perceptions and limited cognitive capacity compromise the ability of researchers to notice new patterns. The present study demonstrates how artificial intelligence can break through identification barriers and generate new estimation modalities. A convolutional neural network was trained with 4003 panoramic-radiographs to sort subjects into 'under-18' and 'over-18' age categories. The resultant architecture identified legal adults with a high predictive accuracy equally balanced between precision, specificity and recall. Moving forward, AI-based methods could improve courtroom efficiency, stand as automated assessment methods and contribute to our understanding of biological ageing.