Viscous dynamics associated with hypoexcitation and structural disintegration in neurodegeneration via generative whole-brain modeling.

INTRODUCTION: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) lack mechanistic biophysical modeling in diverse, underrepresented populations. Electroencephalography (EEG) is a high temporal resolution, cost-effective technique for studying dementia globally, but lacks mechanistic models and produces non-replicable results. METHODS: We developed a generative whole-brain model that combines EEG source-level metaconnectivity, anatomical priors, and a perturbational approach. This model was applied to Global South participants (AD, bvFTD, and healthy controls). RESULTS: Metaconnectivity outperformed pairwise connectivity and revealed more viscous dynamics in patients, with altered metaconnectivity patterns associated with multimodal disease presentation. The biophysical model showed that connectome disintegration and hypoexcitability triggered altered metaconnectivity dynamics and identified critical regions for brain stimulation. We replicated the main results in a second subset of participants for validation with unharmonized, heterogeneous recording settings. DISCUSSION: The results provide a novel agenda for developing mechanistic model-inspired characterization and therapies in clinical, translational, and computational neuroscience settings.

Model-Free Control of a Soft Pneumatic Segment.

Soft robotics faces challenges in attaining control methods that ensure precision from hard-to-model actuators and sensors. This study focuses on closed-chain control of a segment of PAUL, a modular pneumatic soft arm, using elastomeric-based resistive sensors with negative piezoresistive behaviour irrespective of ambient temperature. PAUL's performance relies on bladder inflation and deflation times. The control approach employs two neural networks: the first translates position references into valve inflation times, and the second acts as a state observer to estimate bladder inflation times using sensor data. Following training, the system achieves position errors of 4.59 mm, surpassing the results of other soft robots presented in the literature. The study also explores system modularity by assessing performance under external loads from non-actuated segments.

A cretaceous frog with eggs from northwestern China provides fossil evidence for sexual maturity preceding skeletal maturity in anurans.

Mesozoic fossils of frogs are rare in the palaeontological record, particularly those exhibiting soft tissues that offer limited insights into early life-history characteristics. Here we report on a skeletally immature frog from the Lower Cretaceous of northwest China, with egg masses in the body and eggs in the oviduct, indicative of a gravid female. CT reconstruction of the specimen allows referral to Gansubatrachus qilianensis and we assign it as a paratype complementing the diagnosis of the type species. The new fossil, which might represent a younger individual than the holotype of Gansubatrachus, shows that sexual maturation occurred before full adulthood in this frog and provides evidence of death linked to mating behaviour. We also discuss other potential sources of variation and life-history traits of Gansubatrachus. The new finding represents the oldest Early Cretaceous frog preserving in situ eggs and provides a glimpse into ancient anuran development during Mesozoic times.

Non-invasive diagnosis of diaphragmatic paralysis in botulism using ultrasound.

This case study explores foodborne botulism, a severe illness caused by botulinum neurotoxin-contaminated food. It leads to bilateral descending paralysis, involving the diaphragm. We highlight diaphragmatic ultrasound as a non-invasive diagnostic tool. A 50-year-old obese male developed diplopia and weakness after consuming contaminated food, rapidly progressing to severe symptoms. Mechanical ventilation became necessary due to respiratory failure. Diaphragmatic ultrasound confirmed bilateral diaphragm paralysis despite early antitoxin treatment. The patient experienced complications, requiring tracheostomy and rehabilitation. After five months, he fully recovered diaphragmatic function. This study underscores botulism's life-threatening nature and the vital role of supportive care. Diaphragmatic ultrasound is a safe and effective method for assessing diaphragmatic function in such cases, obviating ionizing radiation exposure. We recommend its routine use for evaluating botulism-induced paralysis.

Neurocognitive correlates of semantic memory navigation in Parkinson's disease.

Cognitive studies on Parkinson's disease (PD) reveal abnormal semantic processing. Most research, however, fails to indicate which conceptual properties are most affected and capture patients' neurocognitive profiles. Here, we asked persons with PD, healthy controls, and individuals with behavioral variant frontotemporal dementia (bvFTD, as a disease control group) to read concepts (e.g., 'sun') and list their features (e.g., hot). Responses were analyzed in terms of ten word properties (including concreteness, imageability, and semantic variability), used for group-level comparisons, subject-level classification, and brain-behavior correlations. PD (but not bvFTD) patients produced more concrete and imageable words than controls, both patterns being associated with overall cognitive status. PD and bvFTD patients showed reduced semantic variability, an anomaly which predicted semantic inhibition outcomes. Word-property patterns robustly classified PD (but not bvFTD) patients and correlated with disease-specific hypoconnectivity along the sensorimotor and salience networks. Fine-grained semantic assessments, then, can reveal distinct neurocognitive signatures of PD.

Predicting mortality in severe Covid-19 Pneumonia: the role of right ventricular dysfunction.

PURPOSE: There is evidence that COVID-19 can have a clinically significant effect on the right ventricle (RV). Our objective was to enhance the efficiency of assessing RV dilation for diagnosing ACP by utilizing both linear measurements and qualitative assessment and its usefulness as an independent predictor of mortality. METHODS: This is an observational, retrospective and single-center study of the Intensive Care Unit of the Sanatorio de Los Arcos in Buenos Aires, Argentina from March 2020 to January 2022. All patients admitted with acute respiratory distress syndrome due to COVID-19 pneumonia (C-ARDS) on mechanical ventilation who were assessed by transthoracic echocardiography (TTE) were included. RESULTS: A total of 114 patients with C-ARDS requiring invasive mechanical ventilation were evaluated by echocardiography. 12.3% had RV dilation defined as a RV basal diameter greater than 41 mm, and 87.7% did not. Acute cor pulmonale (ACP) defined as RV dilation associated with paradoxical septal motion was found in 6.1% of patients. 7% had right ventricular systolic dysfunction according to qualitative evaluation. The different RV echocardiographic variables were studied with a logistic regression model as independent predictors of mortality. In the multivariate analysis, both the RV basal diameter and the presence of ACP showed to be independent predictors of in-hospital mortality with OR of 3.16 (95% CI 1.36-7.32) and 3.64 (95% CI 1.05-12.65) respectively. CONCLUSION: An increase in the RV basal diameter and the presence of ACP measured by TTE are independent predictors of in-hospital mortality in patients with C-ARDS.

The BrainLat project, a multimodal neuroimaging dataset of neurodegeneration from underrepresented backgrounds.

The Latin American Brain Health Institute (BrainLat) has released a unique multimodal neuroimaging dataset of 780 participants from Latin American. The dataset includes 530 patients with neurodegenerative diseases such as Alzheimer's disease (AD), behavioral variant frontotemporal dementia (bvFTD), multiple sclerosis (MS), Parkinson's disease (PD), and 250 healthy controls (HCs). This dataset (62.7 ± 9.5 years, age range 21-89 years) was collected through a multicentric effort across five Latin American countries to address the need for affordable, scalable, and available biomarkers in regions with larger inequities. The BrainLat is the first regional collection of clinical and cognitive assessments, anatomical magnetic resonance imaging (MRI), resting-state functional MRI (fMRI), diffusion-weighted MRI (DWI), and high density resting-state electroencephalography (EEG) in dementia patients. In addition, it includes demographic information about harmonized recruitment and assessment protocols. The dataset is publicly available to encourage further research and development of tools and health applications for neurodegeneration based on multimodal neuroimaging, promoting the assessment of regional variability and inclusion of underrepresented participants in research.

Additive Manufacturing of Fe-Mn-Si-Based Shape Memory Alloys: State of the Art, Challenges and Opportunities.

Additive manufacturing (AM) constitutes the new paradigm in materials processing and its use on metals and alloys opens new unforeseen possibilities, but is facing several challenges regarding the design of the microstructure, which is particularly awkward in the case of functional materials, like shape memory alloys (SMA), as they require a robust microstructure to withstand the constraints appearing during their shape change. In the present work, the attention is focused on the AM of the important Fe-Mn-Si-based SMA family, which is attracting a great technological interest in many industrial sectors. Initially, an overview on the design concepts of this SMA family is offered, with special emphasis to the problems arising during AM. Then, such concepts are considered in order to experimentally develop the AM production of the Fe-20Mn-6Si-9Cr-5Ni (wt%) SMA through laser powder bed fusion (LPBF). The complete methodology is approached, from the gas atomization of powders to the LPBF production and the final thermal treatments to functionalize the SMA. The microstructure is characterized by scanning and transmission electron microscopy after each step of the processing route. The reversibility of the ε martensitic transformation and its evolution on cycling are studied by internal friction and electron microscopy. An outstanding 14% of fully reversible thermal transformation of ε martensite is obtained. The present results show that, in spite of the still remaining challenges, AM by LPBF offers a good approach to produce this family of Fe-Mn-Si-based SMA, opening new opportunities for its applications.

Mechanism of substrate binding and transport in BASS transporters.

The bile acid sodium symporter (BASS) family transports a wide array of molecules across membranes, including bile acids in humans, and small metabolites in plants. These transporters, many of which are sodium-coupled, have been shown to use an elevator mechanism of transport, but exactly how substrate binding is coupled to sodium ion binding and transport is not clear. Here, we solve the crystal structure at 2.3 Å of a transporter from Neisseria meningitidis (ASBTNM) in complex with pantoate, a potential substrate of ASBTNM. The BASS family is characterised by two helices that cross-over in the centre of the protein in an arrangement that is intricately held together by two sodium ions. We observe that the pantoate binds, specifically, between the N-termini of two of the opposing helices in this cross-over region. During molecular dynamics simulations the pantoate remains in this position when sodium ions are present but is more mobile in their absence. Comparison of structures in the presence and absence of pantoate demonstrates that pantoate elicits a conformational change in one of the cross-over helices. This modifies the interface between the two domains that move relative to one another to elicit the elevator mechanism. These results have implications, not only for ASBTNM but for the BASS family as a whole and indeed other transporters that work through the elevator mechanism.

New and previously known ectoparasitic monogenoids (Platyhelminthes) on native and non-native fishes from tributaries of the Usumacinta River basin (southern Mexico), a Neotropical transition zone.

During a research on morphological diversity of gill ectoparasites on native and non-native fishes from tributaries (Palizada, El Recreo and Lacantún rivers) of the Usumacinta River Basin in the states of Campeche, Tabasco, and Chiapas (southern Mexico), the following monogenoids were found: Icelanonchohaptor tropicalis n. sp. on Usumacinta buffalo Ictiobus meridionalis (Günther, 1868) (Catostomidae); Heteropriapulus simplexiodes n. sp. and Heteropriapulus heterotylioides n. sp. on catfishes Pterygoplichthys pardalis (Castelnau, 1855) (Loricariidae) (type host) and Pterygoplichthys disyunctivus (Weber, 1991); Ligictaluridus mirabilis (Mueller 1937; Klassen and Beverley-Burton1985 from the southern blue catfish Ictalurus meridionalis (Günther, 1864) (Ictaluridae); Aristocleidus mexicanus Mendoza-Franco and Vidal-Martínez, 2001 on Eugerres mexicanus (Steindachner, 1863) (Gerreidae) (all monogenoidean species in the Dactylogyridae); and Diplectanocotyla megalopis Rakotofiringa and Oliver1987 (Diplectanidae) on tarpon Megalops atlanticus Valenciennes, 1847 (Megalopidae). The new species of Icelanonchohaptor and Heteropriapulus are herein described for the first time from a native catostomid and non-native Pterygoplichthys spp., respectively. While I. tropicalis n. sp. and L. mirabilis are morphologically comparable with their congeners from the Nearctic (i.e., United States and Canada), all other monogenoids exhibited Neotropical affinities. Present study shown that the gill monogenoids on native and non-native fishes in the Neotropical Mexican transition zone of the Usumacinta River basin are equally represented by species with Nearctic and Neotropical affinities including those adapted to freshwater environment in this area from marine ancestry.

The value of speckle tracking echocardiography in diagnosing minoxidil-induced cardiotoxicity: a case report.

Minoxidil is a drug designed for the treatment of arterial hypotension. Due to its secondary effect of hypertrichosis, it is also used for alopecia treatment. We present a case of a 50-year-old female patient who was orally consuming Minoxidil for medical reasons. She presented with severe hypotension, requiring vasoactive drugs, and evidence of myocardial injury was detected using speckle tracking echocardiography. It is worth noting that the patient did not have any coronary heart disease, and the myocardial injury was found to be associated with Minoxidil consumption. Remarkably, the patient showed signs of reversal 72 h after stopping the drug. To our knowledge, this is the first reported case of subendocardial injury associated with Minoxidil, using speckle tracking echocardiography. In the resolution of the case, it was essential to rule out differential diagnoses, administer vasopressors, and use the speckle tracking echocardiography, which allowed for the objective assessment of myocardial injury and the monitoring of the patient during their hospitalization.

Mechanism of substrate binding and transport in BASS transporters.

The Bile Acid Sodium Symporter (BASS) family transports a wide array of molecules across membranes, including bile acids in humans, and small metabolites in plants. These transporters, many of which are sodium-coupled, have been shown to use an elevator mechanism of transport, but exactly how substrate binding is coupled to sodium ion binding and transport is not clear. Here we solve the crystal structure at 2.3 Å of a transporter from Neisseria Meningitidis (ASBTNM) in complex with pantoate, a potential substrate of ASBTNM. The BASS family is characterised by two helices that cross-over in the centre of the protein in an arrangement that is intricately held together by two sodium ions. We observe that the pantoate binds, specifically, between the N-termini of two of the opposing helices in this cross-over region. During molecular dynamics simulations the pantoate remains in this position when sodium ions are present but is more mobile in their absence. Comparison of structures in the presence and absence of pantoate demonstrates that pantoate elicits a conformational change in one of the cross-over helices. This modifies the interface between the two domains that move relative to one another to elicit the elevator mechanism. These results have implications, not only for ASBTNM but for the BASS family as a whole and indeed other transporters that work through the elevator mechanism.

The neurocognitive impact of loneliness and social networks on social adaptation.

Social adaptation arises from the interaction between the individual and the social environment. However, little empirical evidence exists regarding the relationship between social contact and social adaptation. We propose that loneliness and social networks are key factors explaining social adaptation. Sixty-four healthy subjects with no history of psychiatric conditions participated in this study. All participants completed self-report questionnaires about loneliness, social network, and social adaptation. On a separate day, subjects underwent a resting state fMRI recording session. A hierarchical regression model on self-report data revealed that loneliness and social network were negatively and positively associated with social adaptation. Functional connectivity (FC) analysis showed that loneliness was associated with decreased FC between the fronto-amygdalar and fronto-parietal regions. In contrast, the social network was positively associated with FC between the fronto-temporo-parietal network. Finally, an integrative path model examined the combined effects of behavioral and brain predictors of social adaptation. The model revealed that social networks mediated the effects of loneliness on social adaptation. Further, loneliness-related abnormal brain FC (previously shown to be associated with difficulties in cognitive control, emotion regulation, and sociocognitive processes) emerged as the strongest predictor of poor social adaptation. Findings offer insights into the brain indicators of social adaptation and highlight the role of social networks as a buffer against the maladaptive effects of loneliness. These findings can inform interventions aimed at minimizing loneliness and promoting social adaptation and are especially relevant due to the high prevalence of loneliness around the globe. These findings also serve the study of social adaptation since they provide potential neurocognitive factors that could influence social adaptation.

Evaluating the Utility of Portal Vein Pulsatility Index for Detecting Fluid Unresponsiveness in the Intensive Care Unit.

OBJECTIVE: The primary aim of the authors' study was to evaluate the capacity of the portal vein pulsatility index (PVP) to detect fluid unresponsiveness in patients admitted to intensive care. DESIGN: This was a retrospective, diagnostic accuracy study SETTING: At a tertiary medical-surgical intensive care unit in Buenos Aires, Argentina. PARTICIPANTS: Patients were included during usual care in the intensive care unit, who were evaluated by ultrasonography for the flow of the portal vein, calculating their PVP prior to fluid expansion. INTERVENTIONS: Patients who exhibited an increase of <15% in left ventricle outflow tract velocity-time integral after receiving 500 mL of Ringer Lactate were considered non-responders to fluids. MEASUREMENTS AND MAIN RESULTS: The authors included a total of 63 patients between January 2022 and October 2022. The area under the receiver operating characteristic curve for PVP to predict fluid unresponsiveness was 0.708 (95% CI 0.580 to 0.816). A value of the PVP >32% predicted fluid unresponsiveness with a sensitivity of 30.8% (95% CI 17% to 47.6%) and specificity of 100% (95% CI 85.8 to 100). The positive predictive value was 100%, and the negative predictive value was 47.1% (95% CI 41.9% to 52.3%). CONCLUSIONS: Although PVP has limited value as the sole indicator for fluid management decisions, it can be used as a stopping rule or combined with other diagnostic tests to improve the accuracy of fluid responsiveness assessment.

Multiclass characterization of frontotemporal dementia variants via multimodal brain network computational inference.

Characterizing a particular neurodegenerative condition against others possible diseases remains a challenge along clinical, biomarker, and neuroscientific levels. This is the particular case of frontotemporal dementia (FTD) variants, where their specific characterization requires high levels of expertise and multidisciplinary teams to subtly distinguish among similar physiopathological processes. Here, we used a computational approach of multimodal brain networks to address simultaneous multiclass classification of 298 subjects (one group against all others), including five FTD variants: behavioral variant FTD, corticobasal syndrome, nonfluent variant primary progressive aphasia, progressive supranuclear palsy, and semantic variant primary progressive aphasia, with healthy controls. Fourteen machine learning classifiers were trained with functional and structural connectivity metrics calculated through different methods. Due to the large number of variables, dimensionality was reduced, employing statistical comparisons and progressive elimination to assess feature stability under nested cross-validation. The machine learning performance was measured through the area under the receiver operating characteristic curves, reaching 0.81 on average, with a standard deviation of 0.09. Furthermore, the contributions of demographic and cognitive data were also assessed via multifeatured classifiers. An accurate simultaneous multiclass classification of each FTD variant against other variants and controls was obtained based on the selection of an optimum set of features. The classifiers incorporating the brain's network and cognitive assessment increased performance metrics. Multimodal classifiers evidenced specific variants' compromise, across modalities and methods through feature importance analysis. If replicated and validated, this approach may help to support clinical decision tools aimed to detect specific affectations in the context of overlapping diseases.

The impact of loneliness and social adaptation on depressive symptoms: Behavioral and brain measures evidence from a brain health perspective.

Introduction: Early detection of depression is a cost-effective way to prevent adverse outcomes on brain physiology, cognition, and health. Here we propose that loneliness and social adaptation are key factors that can anticipate depressive symptoms. Methods: We analyzed data from two separate samples to evaluate the associations between loneliness, social adaptation, depressive symptoms, and their neural correlates. Results: For both samples, hierarchical regression models on self-reported data showed that loneliness and social adaptation have negative and positive effects on depressive symptoms. Moreover, social adaptation reduces the impact of loneliness on depressive symptoms. Structural connectivity analysis showed that depressive symptoms, loneliness, and social adaptation share a common neural substrate. Furthermore, functional connectivity analysis demonstrated that only social adaptation was associated with connectivity in parietal areas. Discussion: Altogether, our results suggest that loneliness is a strong risk factor for depressive symptoms while social adaptation acts as a buffer against the ill effects of loneliness. At the neuroanatomical level, loneliness and depression may affect the integrity of white matter structures known to be associated to emotion dysregulation and cognitive impairment. On the other hand, socio-adaptive processes may protect against the harmful effects of loneliness and depression. Structural and functional correlates of social adaptation could indicate a protective role through long and short-term effects, respectively. These findings may aid approaches to preserve brain health via social participation and adaptive social behavior.

Hypothalamic-pituitary-gonadal axis disturbance and its association with insulin resistance in kidney transplant recipients / Distúrbio do eixo hipotálamo-hipófise-gonadal e sua associação com resistência à insulina em receptores de transplante renal

Abstract Objective: To evaluate hypothalamic-pi- tuitary-gonadal (HPG) axis alterations at 1 and 12 months after kidney transplan- tation (KT) and their association with in- sulin resistance. Methods: A retrospective clinical study was conducted in a tertiary care center in kidney transplantation recipients (KTRs) aged 18- 50 years with primary kidney disease and stable renal graft function. LH, FSH, E2/T, and HOMA-IR were assessed at 1 and 12 months after KT. Results: Twenty-five KTRs were included; 53% were men, and the mean age was 30.6±7.7 years. BMI was 22.3 (20.4-24.6) kg/m2, and 36% had hypogonadism at 1 month vs 8% at 12 months (p=0.001). Re- mission of hypogonadism was observed in all men, while in women, hypogonadotropic hypogonadism persisted in two KTRs at 12 months. A positive correlation between go- nadotrophins and age at 1 and 12 months was evident. Fifty-six percent of patients had insulin resistance (IR) at 1 month and 36% at 12 months (p=0.256). HOMA-IR showed a negative correlation with E2 (r=- 0.60; p=0.050) and T (r=-0.709; p=0.049) at 1 month, with no correlation at 12 months. HOMA-IR at 12 months after KT correlated positively with BMI (r=0.52; p=0.011) and tacrolimus dose (r=0.53; p=0.016). Conclusion: Successful KT restores the HPG axis in the first year. Hypogonadism had a negative correlation with IR in the early pe- riod after KT, but it was not significant at 12 months.

Resumo Objetivo: Avaliar as alterações do eixo hipotálamo-hipófise-gonadal (HHG) em 1 e 12 meses após transplante renal (TR) e sua associação com a resistência à insulina. Métodos: Foi realizado um estudo clínico retrospectivo em um centro de cuidados terciários em receptores de transplante renal (RTR) com idade entre 18-50 anos com doença renal primária e função do enxerto renal estável. LH, FSH, E2/T e HOMA-IR foram avaliados em 1 e 12 meses após o TR. Resultados: foram incluídos 25 RTR; 53% eram homens e a média de idade foi de 30,6±7,7 anos. O IMC foi de 22,3 (20,4-24,6) kg/m2 e 36% apresentaram hipogonadismo em 1 mês vs 8% aos 12 meses (p=0,001). A remissão do hipogonadismo foi observada em todos os homens, enquanto nas mulheres, o hipogonadismo hipogonadotrófico persistiu em dois RTR aos 12 meses. Ficou evidente uma correlação positiva entre gonadotrofinas e idade em 1 e 12 meses. Cinquenta e seis por cento dos pacientes apresentaram resistência à insulina (RI) em 1 mês e 36% aos 12 meses (p=0,256). O HOMA-IR mostrou uma correlação negativa com E2 (r=-0,60; p=0,050) e T (r=-0,709; p=0,049) em 1 mês, sem correlação em 12 meses. O HOMA-IR aos 12 meses após TR correlacionou-se positivamente com o IMC (r=0,52; p=0,011) e a dose de tacrolimus (r=0,53; p=0,016). Conclusão: O TR bem-sucedido restaura o eixo HHG no primeiro ano. O hipogonadismo apresentou uma correlação negativa com a RI no período inicial após o TR, mas essa correlação não foi significativa aos 12 meses.