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Moises das Virgens Santana,1 Maria Beatriz S Magulas,1 Guilherme Castro Brito,1 Mariana Chaves Santos,1 Tainara Gomes de Oliveira,1 Wanderson Gabriel Gomes de Melo,2 Napoleao Martins Argolo Neto,2 Fernanda Roberta Marciano,1,3 Bartolomeu Cruz Viana,1,3 Anderson Oliveira Lobo1 1LIMAV-Interdisciplinary Laboratory for Advanced Materials, UFPI - Federal University of Piaui, Teresina, PI, 64049-550, Brazil; 2Integrated Center for Morphology and Stem Cell Research, Postgraduate Program in Technologies Applied to Animals of Regional Interest, Federal University of Piaui, Teresina, PI, 64049-550, Brazil; 3Department of Physics, UFPI - Federal University of Piaui, Teresina, PI, 64049-550, BrazilCorrespondence: Anderson Oliveira Lobo, Email lobo@ufpi.edu.brPurpose: Tissue engineering aims to recreate natural cellular environments to facilitate tissue regeneration. Gelatin methacrylate (GelMA) is widely utilized for its biocompatibility, ability to support cell adhesion and proliferation, and adjustable mechanical characteristics. This study developed a GelMA and graphene bioink platform at concentrations of 1, 1.5, and 2 mg/mL to enhance scaffold properties for tissue engineering applications.Patients and Methods: Graphene was incorporated into GelMA matrices to improve mechanical strength and electrical conductivity of the bioinks. The compressive strength and thermal stability of the resulting GelMA/graphene scaffolds were assessed through DSC analysis and mechanical testing. Cytotoxicity assays were conducted to determine cell survival rates. Cryoprinting at − 30°C was employed to preserve scaffold structure and function. The chorioallantoic membrane (CAM) assay was used to evaluate biocompatibility and angiogenic potential.Results: The integration of graphene significantly amplified the compressive strength and thermal stability of GelMA scaffolds. Cytotoxicity assays indicated robust cell survival rates of 90%, confirming the biocompatibility of the developed materials. Cryoprinting effectively preserved scaffold integrity and functionality. The CAM assay validated the biocompatibility and angiogenic potential, demonstrating substantial vascularization upon scaffold implantation onto chick embryo CAM.Conclusion: Integrating graphene into GelMA hydrogels, coupled with low-temperature 3D printing, represents a potent strategy for enhancing scaffold fabrication. The resultant GelMA/graphene scaffolds exhibit superior mechanical properties, biocompatibility, and pro-vascularization capabilities, making them highly suitable for diverse tissue engineering and regenerative medicine applications.Keywords: GelMA, graphene, cryoprinting, hydrogels and tissue engineering

Anethole, an antioxidant found in plants, appears to improve the survival of spermatozoa during semen cryopreservation. This study assessed the effects of commercial trans-anethole in ram semen cryopreservation. Thirty ejaculates from six rams were diluted in media containing anethole at the following concentrations: CONT (0 μM), AN10 (10 μM), AN50 (50 μM), and AN100 (100 μM). Semen was slow-frozen, preserved in liquid nitrogen, and thawed. Anethole at 10 μM or 50 μM did not compromise any studied sperm quality parameter but increased pre-freezing functionality of membrane and mitochondrial activity. At 10 μM, anethole reduced post-thawing spermatozoa lipoperoxidation. At 50 μM, anethole sustained higher mitochondrial activity after thawing, reduced minor defects in sperm, and increased the number of sperm binding to perivitelline membrane, while keeping lipoperoxidation levels as in control. Anethole at 100 μM promoted higher pre- and post-freezing mitochondrial activity and higher number of sperm binding to perivitelline membrane, in comparison to control. Additionally, some post-thawing kinematic parameters were enhanced by anethole at 100 μM. Of note, mitochondrial activity and lipoperoxidation were higher with anethole at 100 μM in comparison to 50 μM, not differing from control. At the hypoosmotic test, the highest concentration (100 μM) tested reduced sperm osmotic resistance. The results of this study indicate that using anethole in cryopreservation media promoted mostly positive effects on the fresh and post-thawed ram semen, and the advantages vary according to its concentration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Brain vascular pathology is an important comorbidity in Alzheimer's disease (AD), with white matter damage independently predicting cognitive impairment. However, it is still unknown how vascular pathology differentially impacts primary age-related tauopathy (PART) compared to AD. Therefore, our objectives were to compare the brain microangiopathic burden in patients with PART and AD, evaluated by MRI, while assessing its relation with neuropathological findings, patterns of brain atrophy and degree of clinical impairment., Methods: Clinical information, brain MRI (T1 and T2-FLAIR) and neuropathological data were obtained from the National Alzheimer's Coordinating Centre ongoing study, with a total sample of 167 patients identified, that were divided according to the presence of neuritic plaques in Consortium to Establish a Registry for Alzheimer's disease (CERAD) 0 to 3. Microangiopathic burden and brain atrophy were evaluated by two certified neuroradiologists, using, respectively, the Fazekas score and previously validated visual rating scales to assess brain regional atrophy., Results: Significant correlations were found between the Fazekas score and atrophy in the fronto-insular and medial temporal regions on both groups, with PART showing overall stronger positive correlations than in AD, especially in the fronto-insular region. For this specific cohort, no significant correlations were found between the Fazekas score and the degree of clinical impairment., Conclusion: Our results show that PART presents different pathological consequences at the brain microvascular level compared with AD and further supports PART as an independent pathological entity from AD., Competing Interests: Declarations. Ethics approval: Study protocols were approved by the respective institutional review boards at each local Alzheimer’s Disease Centers. Informed consent: Written informed consent was provided by all participants at each local Alzheimer’s Disease Centers, and participants that contributed to the National Alzheimer’s Coordinating Center Neuropathology Data Set gave consent to autopsy. Competing interests: M.Q.N. is an Editorial Board Member of this journal, namely in Head and Neck/ENT Radiology Section. T.G.O. is a scientific advisor and shareholder of Ceracuity Inc, has been a consultant for Sonae and Guidepoint, has received fees as a speaker from Eisai and conference fees covered from Roche., (© 2024. The Author(s).)

The precise neurophysiological changes prompted by meningeal lymphatic dysfunction remain unclear. Here, we showed that inducing meningeal lymphatic vessel ablation in adult mice led to gene expression changes in glial cells, followed by reductions in mature oligodendrocyte numbers and specific lipid species in the brain. These phenomena were accompanied by altered meningeal adaptive immunity and brain myeloid cell activation. During brain remyelination, meningeal lymphatic dysfunction provoked a state of immunosuppression that contributed to delayed spontaneous oligodendrocyte replenishment and axonal loss. The deficiencies in mature oligodendrocytes and neuroinflammation due to impaired meningeal lymphatic function were solely recapitulated in immunocompetent mice. Patients diagnosed with multiple sclerosis presented reduced vascular endothelial growth factor C in the cerebrospinal fluid, particularly shortly after clinical relapses, possibly indicative of poor meningeal lymphatic function. These data demonstrate that meningeal lymphatics regulate oligodendrocyte function and brain myelination, which might have implications for human demyelinating diseases., Competing Interests: Declaration of interests S.D.M. is listed as an inventor in patents and patent applications concerning modulating lymphatic vessels in neurological diseases (University of Virginia Licensing & Ventures Group and PureTech Ventures LLC). S.R.I. has received honoraria/research support from UCB, Immunovant, MedImmun, Roche, Janssen, Cerebral therapeutics, ADC therapeutics, Brain, CSL Behring, and ONO Pharma, receives licensed royalties on patent application WO/2010/046716 entitled “Neurological Autoimmune Disorders,” and has filed two other patents entitled “Diagnostic method and therapy” (WO2019211633 and US-2021-0071249-A1; PCT application WO202189788A1) and “Biomarkers” (PCT/GB2022/050614 and WO202189788A1)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Montane cloud forests are highly threatened ecosystems that are vulnerable to climate change. These complex habitats harbor many species that suffer the negative consequences of this global phenomenon, such as shifts in their distribution and habitat use. The Central American clouded oncilla (Leopardus pardinoides oncilla) is the smallest and most endangered wild cat in Mesoamerica and is primarily reported in cloud forests throughout its distribution. The species is poorly understood, with no studies conducted in Central America assessing its habitat preferences. To bridge this knowledge gap, we sampled two mountain ranges in Costa Rica with camera traps and conducted an occupancy analysis to understand the anthropogenic and environmental features that influence oncilla habitat use within them. Additionally, we conducted spatial predictions of habitat use across its northern and southern range in Costa Rica to identify priority conservation areas for the species. We found that Central American clouded oncilla habitat use is driven primarily by environmental factors. Our results showed that oncillas select habitats with denser tree cover at high elevations, closer to permanent water sources, which may provide them with high prey density and a favorable habitat structure for their survival. Spatial predictions identified two main regions as conservation priority areas where threat mitigation efforts and monitoring should be implemented: the Caribbean slope of the Talamanca mountains, and the Arenal-Monteverde forest complex. The occupancy modeling approach turned out to be very useful to assess the spatial associations of the species with the environment and mapping the conservation priority areas. Future research and mitigation actions should focus on potential threats that could negatively impact Central American clouded oncilla populations and habitat use, including the role of mesopredators and feral species., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ramírez-Fernández et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Unraveling how Alzheimer's disease (AD) genetic risk is related to neuropathological heterogeneity, and whether this occurs through specific biological pathways, is a key step toward precision medicine., Methods: We computed pathway-specific genetic risk scores (GRSs) in non-demented individuals and investigated how AD risk variants predict cerebrospinal fluid (CSF) and imaging biomarkers reflecting AD pathology, cardiovascular, white matter integrity, and brain connectivity., Results: CSF amyloidbeta and phosphorylated tau were related to most GRSs. Inflammatory pathways were associated with cerebrovascular disease, whereas quantitative measures of white matter lesion and microstructure integrity were predicted by clearance and migration pathways. Functional connectivity alterations were related to genetic variants involved in signal transduction and synaptic communication., Discussion: This study reveals distinct genetic risk profiles in association with specific pathophysiological aspects in predementia stages of AD, unraveling the biological substrates of the heterogeneity of AD-associated endophenotypes and promoting a step forward in disease understanding and development of personalized therapies., Highlights: Polygenic risk for Alzheimer's disease encompasses six biological pathways that can be quantified with pathway-specific genetic risk scores, and differentially relate to cerebrospinal fluid and imaging biomarkers. Inflammatory pathways are mostly related to cerebrovascular burden. White matter health is associated with pathways of clearance and membrane integrity, whereas functional connectivity measures are related to signal transduction and synaptic communication pathways., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Mucopolysaccharidoses (MPS) are rare metabolic diseases that impair respiratory function leading to respiratory failure. This study aimed to compare maximal inspiratory and expiratory pressures (MIP and MEP) obtained in children with MPS and compare with predicted values from previous studies involving healthy children., Methods: This is a cross-sectional study, in which the chest deformity was evaluated; MIP, MEP through digital manometer, and lung function through spirometry. MIP and MEP were compared with five different predict equations and with a control group of healthy children. Agreement between respiratory muscle weakness regarding absolute values of MIP and MEP in relation to predictive values by the equations included in the study were assessed by Kappa coefficient., Results: MPS group was composed of 22 subjects. 45.5% had pectus carinatum, 36.4% pectus excavatum, and presented lower MIP (37.14±36.23 cmH2O) and MEP (60.09±22.3 cmH2O) compared with control group (22 healthy subjects) (MIP: 91.45±35.60; MEP: 95.73±22.38). Only the MEP equations proposed by Tomalak et al. were close to those found in our MPS children (P=0.09). In the MPS group it was observed a weak agreement between inspiratory weakness through absolute and predicted values in only two equations: Tomalak et al. and Domenèch-Clar et al. (for both: k=0.35, P value =0.03); and for MEP a moderate agreement was found using all predictive equations., Conclusions: In MPS children MRP data should not be normalized using the reference equations for healthy ones, is more coherent to longitudinally follow absolute pressures and lung volumes in this group.

Background: Antibodies against leucine-rich glioma inactivated protein 1 (LGI1) constitute a common form of autoimmune encephalitis. On MR imaging, it may show T2 FLAIR hyperintensities of the medial temporal lobe (T2 FLAIR-MTL), involve the basal ganglia, or be unremarkable., Purpose: We performed a systematic review and meta-analysis to obtain prevalence estimates of abnormal findings on MR imaging in anti-LGI1 encephalitis. A human brain map of the LGI1 microarray gene expression was derived from the Allen Human Brain Atlas., Data Sources: PubMed and Web of Science were searched with the terms "LGI1" and "encephalitis" from inception to April 7, 2022., Study Selection: Thirty-one research publications, encompassing case series and retrospective cohort and case-control studies, with >10 patients with anti-LGI1 encephalitis and MR imaging data were included., Data Analysis: Pooled prevalence estimates were calculated using Freeman-Tukey double-arcsine transformation. Meta-analysis used DerSimonian and Laird random effects models., Data Synthesis: Of 1318 patients in 30 studies, T2 FLAIR-MTL hyperintensities were present in 54% (95% CI, 0.48-0.60; I 2 = 76%). Of 394 patients in 13 studies, 27% showed bilateral (95% CI, 0.19-0.36; I 2 = 71%) and 24% unilateral T2 FLAIR-MTL abnormalities (95% CI, 0.17-0.32; I 2 = 61%). Of 612 patients in 15 studies, basal ganglia abnormalities were present in 10% (95% CI, 0.06-0.15; I 2 = 67%). LGI1 expression was highest in the amygdala, hippocampus, and caudate nucleus., Limitations: Only part of the spectrum of MR imaging abnormalities in anti-LGI1 encephalitis could be included in a meta-analysis. MR imaging findings were not the main outcomes in most studies, limiting available information. I 2 values ranged from 62% to 76%, representing moderate-to-large heterogeneity., Conclusions: T2 FLAIR-MTL hyperintensities were present in around one-half of patients with anti-LGI1. The prevalence of unilateral and bilateral presentations was similar, suggesting unilaterality should raise the suspicion of this disease in the appropriate clinical context. Around 10% of patients showed basal ganglia abnormalities, indicating that special attention should be given to this region. LGI1 regional expression coincided with the most frequently reported abnormal findings on MR imaging. Regional specificity might be partially determined by expression levels of the target protein., (© 2024 by American Journal of Neuroradiology.)

Competing Interests: Declaration of competing interest We would like to inform that the authors of the manuscript entitled “Effects of whole-body vibration exercise on functional capacity, muscle strength and thickness, and quality of life of post-COVID-19 patients: Case report” have no conflict of interest and all the authors assume the responsibility for this paper.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that primarily affects the hippocampus. Since hippocampal studies have highlighted a differential subregional regulation along its longitudinal axis, a more detailed analysis addressing subregional changes along the longitudinal hippocampal axis has the potential to provide new relevant biomarkers. This study included structural brain MRI data of 583 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cognitively normal (CN) subjects, mild cognitively impaired (MCI) subjects and AD patients were conveniently selected considering the age and sex match between clinical groups. Structural MRI acquisitions were pre-processed and analysed with a new longitudinal axis segmentation method, dividing the hippocampus in three subdivisions (anterior, intermediate, and posterior). When normalizing the volume of hippocampal sub-divisions to total hippocampus, the posterior hippocampus negatively correlates with age only in CN subjects (r = -.31). The longitudinal ratio of hippocampal atrophy (anterior sub-division divided by the posterior one) shows a significant increase with age only in CN (r = .25). Overall, in AD, the posterior hippocampus is predominantly atrophied early on. Consequently, the anterior/posterior hippocampal ratio is an AD differentiating metric at early disease stages with potential for diagnostic and prognostic applications., (© 2024 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Psychosis in Alzheimer's Disease (AD) is prevalent and indicates poor prognosis. However, the neuropathological, cognitive and brain atrophy patterns underlying these symptoms have not been fully elucidated. In this study, we evaluated 178 patients with AD neuropathological change (ADNC) and ante-mortem volumetric brain magnetic resonance imaging (MRI). Presence of psychosis was determined using the Neuropsychiatric Inventory Questionnaire. Clinical Dementia Rating Sum-of-boxes (CDR-SB) was longitudinally compared between groups with a follow-up of 3000 days using mixed-effects multiple linear regression. Neuropsychological tests closest to the time of MRI and brain regional volumes were cross-sectionally compared. Psychosis was associated with lower age of death, higher longitudinal CDR-SB scores, multi-domain cognitive deficits, higher neuritic plaque severity, Braak stage, Lewy Body pathology (LB) and right temporal lobe regional atrophy. Division according to the presence of LB showed differential patterns of AD-typical pathology, cognitive deficits and regional atrophy. In conclusion, psychosis in ADNC with and without LB has clinical value and associates with subgroup patterns of neuropathology, cognition and regional atrophy., (Copyright © 2024. Published by Elsevier Inc.)

AbstractLocomotion is essential for survival, but it requires resources such as energy and metabolites and therefore may conflict with other physiological processes that also demand resources, particularly expensive processes such as immunological responses. This possible trade-off may impose limits on either the magnitude of immune responses or the patterns of activity and performance. Previous studies have shown that invasive species may have a depressed immune response, allowing them to maintain locomotor function and reproduction even when sick. This may contribute to the ecological success of invasive species in colonization and dispersal. In contrast, noninvasive species tend to reduce activity as a response to infection. Here, we studied the impact of a simulated infection on locomotor performance and voluntary movement in the anurans Xenopus laevis (a globally invasive species) and Xenopus allofraseri (a noninvasive congeneric). We found that a simulated infection reduces locomotor performance in both species, with an accentuated effect on X. allofraseri . Voluntary movement was marginally different between species. Our data suggest that a simulated infection leads to behavioral depression and reduced locomotor performance in anurans and show that this effect is limited in the invasive X. laevis . Contrasting responses to an immune challenge have been reported in the few amphibian taxa analyzed to date and suggest relationships between ecology and immunology that deserve further investigation. Specifically, a depressed immune response may underlie a propension to invasion in some species. Whether this is a general trend for invasive species remains to be tested, but our data add to the growing body of work documenting depressed immune systems in invasive species.

Apolipoprotein E (APOE) genetic variants are most notably known for their divergent impact on the risk of developing Alzheimer's disease. While APOE genotype has been consistently shown to modulate lipid metabolism in a variety of cellular contexts, the effect of APOE alleles on the lipidome in hepatocytes is unknown. In this study, we investigated the contribution of APOE alleles to lipidomic profiles of donor-derived primary human hepatocytes from 77 subjects. Lipidomic data obtained by liquid chromatography-mass spectrometry were analyzed across ε2/ε3, ε3/ε3, and ε3/ε4 genotypes to reveal how APOE modulates lipid relative levels over age and between groups. Hepatic APOE concentration, measured by ELISA, was assessed for correlation with lipid abundance in subjects grouped as per APOE genotype and sex. APOE genotype-specific differential lipidomic signatures associated with age for multiple lipid classes but did not differ between sexes. Compared to ε2/ε3, ε3/ε4 hepatocytes had higher abundance of acylcarnitines (AC) and acylphosphatidylglycerol (AcylPG) as a class, as well as higher medium and long-chain ACs, AcylPG, phosphatidylglycerol (PG), bis(monoacylglycerol)phosphate (BMP), monoacylglycerol (MG) and diacylglycerol (DG) species. The ε3/ε4 hepatocytes also exhibited a higher abundance of medium and long-chain ACs compared to the ε3/ε3 hepatocytes. Only in the ε3/ε4 hepatocytes, APOE concentration was lower and showed a negative correlation with BMP levels, specifically in females. APOE genotype dictates a differential lipidome in primary human hepatocytes. The lipids involved suggest mitochondrial dysfunction with accompanying alterations in neutral lipid storage, reflective of a general disturbance of free fatty acid metabolism in human hepatocytes with the ε4 allele., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Recently, the tiger-cat species complex was split into Leopardus tigrinus and Leopardus guttulus, along with other proposed schemes. We performed a detailed analysis integrating ecological modeling, biogeography, and phenotype of the four originally recognized subspecies-tigrinus, oncilla, pardinoides, guttulus-and presented a new multidimensional niche depiction of the species. Species distribution models used > 1400 records from museums and photographs, all checked for species accuracy. Morphological data were obtained from institutional/personal archives. Spotting patterns were established by integrating museum and photographic/camera-trap records. Principal component analysis showed three clearly distinct groups, with the Central American specimens (oncilla) clustering entirely within those of the Andes, namely the pardinoides group of the cloud forests of the southern Central-American and Andean mountain chains (clouded tiger-cat); the tigrinus group of the savannas of the Guiana Shield and central/northeastern Brazil (savanna tiger-cat); and the guttulus group in the lowland forests of the Atlantic Forest domain (Atlantic Forest tiger-cat). This scheme is supported by recent genetic analyses. All species displayed different spotting patterns, with some significant differences in body measurements/proportions. The new distribution presented alarming reductions from the historic range of - 50.4% to - 68.2%. This multidimensional approach revealed a new species of the elusive and threatened tiger-cat complex., (© 2024. The Author(s).)

Growth and maturation are central concerns in the organization of training and competitions in youth sports. This study examined maturity-associated variation in body size and adiposity among adolescent girls participating in competitive age group youth soccer. The sample included 441 players 10.08-16.73 years of age. Stature and body mass were measured and body composition was predicted. The Fels method was used to estimate skeletal age. Skeletally maturity status (late, average or early maturing) was based on the difference between chronological and skeletal age for each player. Mean stature approximated the 50 th percentiles of the general population in all competitive age groups, while mean weight fluctuated between 50 th and 75 th percentiles. Age- and maturity-specific means for estimated fat mass ranged between 18.0% and 28.2%. The number of players classified as skeletally mature increased with competitive age groups (under-13: 0%; under-15: 8%; under-17: 49%). In general, early maturing girls tended to be heavier than their age group peers and especially when compared to late maturing players., Competing Interests: Statement The authors report no conflict of interest, (Thieme. All rights reserved.)

Mesocarnivores play a key role in ecosystem dynamics through the regulation of prey populations and are sensitive to environmental changes; thus, they are often considered good model organisms for conservation planning. However, data regarding the factors that influence the habitat use of threatened small wild felids such as the Andean tiger cat (Leopardus tigrinus pardinoides) are scarce. We conducted a two-year survey with 58 camera trap stations to evaluate the determinants of Andean tiger cat habitat use in three protected areas in the Middle Cauca, Colombia. We developed site occupancy models and found that Andean tiger cat habitat use increased with leaf litter depth at intermediate elevations and far from human settlements. Through conditional cooccurrence models, we found that Andean tiger cat habitat use was invariant to the presence of prey or potential intraguild competitors and killers/predators, but its detectability increased when they were present and detected. This suggests that Andean tiger cats may be more likely to be detected in sites with high prey availability. We found that Andean tiger cats preferred sites with deep leaf litter, which is a particular feature of cloud forests that provides suitable conditions for ambush hunting and hiding from intraguild enemies. Our results showed that Andean tiger cats avoided human settlements, which may minimize potential mortality risks in those areas. Moreover, the restricted use of middle elevations by Andean tiger cats suggested that they could be used as a sentinel species to track the effects of climate change since their suitable habitat is likely to be projected upward in elevation. Future conservation actions must be focused on identifying and mitigating human-related threats close to the Andean tiger cat habitat while preserving microhabitat conditions and the existing networks of protected areas., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Cepeda-Duque et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Purpose: Cerebral amyloid angiopathy is characterized by amyloid β deposition in leptomeningeal and superficial cortical vessels. Cognitive impairment is common and may occur independent of concomitant Alzheimer disease neuropathology. It is still unknown which neuroimaging findings are associated with dementia in cerebral amyloid angiopathy and whether they are modulated by sex. This study compared MR imaging markers in patients with cerebral amyloid angiopathy with dementia or mild cognitive impairment or who are cognitively unimpaired and explored sex-specific differences., Materials and Methods: We studied 58 patients with cerebral amyloid angiopathy selected from the cerebrovascular and memory outpatient clinics. Clinical characteristics were collected from clinical records. Cerebral amyloid angiopathy was diagnosed on MR imaging on the basis of the Boston criteria. Visual rating scores for atrophy and other imaging features were independently assessed by 2 senior neuroradiologists., Results: Medial temporal lobe atrophy was higher for those with cerebral amyloid angiopathy with dementia versus those cognitively unimpaired ( P = .015), but not for those with mild cognitive impairment. This effect was mainly driven by higher atrophy in men with dementia, compared with women with and without dementia ( P = .034, P = .012; respectively) and with men without dementia ( P = .012). Enlarged perivascular spaces in the centrum semiovale were more frequent in women with dementia versus men with and without dementia ( P = .021, P = .011; respectively) and women without dementia ( P = .011)., Conclusions: Medial temporal lobe atrophy was more prominent in men with dementia, whereas women showed a higher number of enlarged perivascular spaces in the centrum semiovale. Overall, this finding suggests differential pathophysiologic mechanisms with sex-specific neuroimaging patterns in cerebral amyloid angiopathy., (© 2023 by American Journal of Neuroradiology.)

Paper-based electrochemical analytical devices (ePADs) have gained significant interest as promising analytical units in recent years because they can be fabricated in simple ways, are low-cost, portable, and disposable platforms that can be applied in various fields. In this sense, paper-based electrochemical biosensors are attractive analytical devices since they can promote diagnose several diseases and potentially allow decentralized analysis. Electrochemical biosensors are versatile, as the measured signal can be improved by using mainly molecular technologies and nanomaterials to attach biomolecules, resulting in an increase in their sensitivity and selectivity. Additionally, they can be implemented in microfluidic devices that drive and control the flow without external pumping and store reagents, and improve the mass transport of analytes, increasing sensor sensitivity. In this review, we focus on the recent developments in electrochemical paper-based devices for viruses' detection, including COVID-19, Dengue, Zika, Hepatitis, Ebola, AIDS, and Influenza, among others, which have caused impacts on people's health, especially in places with scarce resources. Also, we discuss the advantages and disadvantages of the main electrode's fabrication methods, device designs, and biomolecule immobilization strategies. Finally, the perspectives and challenges that need to be overcome to further advance paper-based electrochemical biosensors' applications are critically presented., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Early Alzheimer's disease (AD) is associated with hippocampal hyperactivity and decreased sleep quality. Here we show that homeostatic mechanisms transiently counteract the increased excitatory drive to CA1 neurons in App NL-G-F mice, but that this mechanism fails in older mice. Spatial transcriptomics analysis identifies Pmch as part of the adaptive response in App NL-G-F mice. Pmch encodes melanin-concentrating hormone (MCH), which is produced in sleep-active lateral hypothalamic neurons that project to CA1 and modulate memory. We show that MCH downregulates synaptic transmission, modulates firing rate homeostasis in hippocampal neurons and reverses the increased excitatory drive to CA1 neurons in App NL-G-F mice. App NL-G-F mice spend less time in rapid eye movement (REM) sleep. App NL-G-F mice and individuals with AD show progressive changes in morphology of CA1-projecting MCH axons. Our findings identify the MCH system as vulnerable in early AD and suggest that impaired MCH-system function contributes to aberrant excitatory drive and sleep defects, which can compromise hippocampus-dependent functions., (© 2023. The Author(s).)

Objective  Research and identification of Cutibacterium acnes ( C. acnes ) and other microorganisms in deep tissue samples collected in clean shoulder surgeries of patients who did not undergo any previous invasive joint procedure and who had no clinical history of infection. Methods  We analyzed the results of cultures of intraoperative deep tissue samples from 84 patients submitted to primary clean shoulder surgery. Tubes containing culture medium were used for storage and transport of anaerobic agents, prolonged incubation time, and mass spectrometer for diagnosis of bacterial agents. Results  Bacteria growth was evidenced in 34 patients (40.4%) of the 84 included in the study. Of these, 23 had growth of C. acnes in at least one sample of deep tissue collected, corresponding to 27.3% of the total patients. The second most common agent was Staphylococcus epidermidis , present in 7.2% of the total individuals included. We showed a higher relationship between sample positivity and males, a lower mean age, absence of diabetes mellitus, ASA I score, and antibiotic prophylaxis in anesthetic induction with cefuroxime. Conclusions  A high percentage of isolates of different bacteria was found in shoulder tissue samples of patients undergoing clean and primary surgeries, who had no history of previous infection. Identification of C. acnes was high (27.6%), and Staphylococcus epidermidis was the second most frequent agent (7.2%)., Competing Interests: Conflito de Interesses Os autores declaram não haver conflito de interesses., (Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

The semi-arid Caatinga is the largest dry forest ecoregion in the Americas; nevertheless, it is experiencing alarming rates of habitat loss. Most vegetation fragments in the biome are either unprotected or within private lands; however, these private areas are susceptible to anthropogenic activity, and often have the presence of non-native wildlife such as domestic dogs and cats. Two small felid species, the northern tiger cat and the jaguarundi co-occur throughout the Caatinga and have overlapping niches, which require segregation mechanisms to avoid interference competition. Assessing these species strategies for coexistence is crucial, as it can guide conservation actions. With this aim, a private ranch in the Brazilian Caatinga drylands was surveyed and multi-species occupancy models were used to assess co-occurrence patterns between northern tiger cats and jaguarundis. The degree of temporal overlap between both felids and domestic dogs and cats were also assessed. Evidence was found of positive co-occurrence between tiger cats and jaguarundis, suggesting a lack of spatial segregation at our study site; and low temporal overlap was found between both felids, with tiger cats being nocturnal and jaguarundis diurnal. High temporal overlap was found though between domestic dogs and both wild felid species. Our results suggest that small felids can coexist in private areas of the Caatinga with sufficient habitat. However, there is a need to highlight the potential threat of disease transmission by non-native carnivores as something that should be addressed in these private landscapes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Fox-Rosales, de Oliveira. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Titanate nanotubes were synthesized and subjected to an ion exchange reaction with erbium salt aqueous solution to obtain titanate nanotubes exchanged with erbium (3+) ions. In order to evaluate the effects of the thermal treatment atmosphere on the structural and optical properties of erbium titanate nanotubes, we subjected them to heat treatment in air and argon atmospheres. For comparison, titanate nanotubes were also treated in the same conditions. A complete structural and optical characterizations of the samples was performed. The characterizations evidenced the preservation of the morphology with the presence of phases of erbium oxides decorating the surface of the nanotubes. Variations in the dimensions of the samples (diameter and interlamellar space) were promoted by the replacement of Na + by Er 3+ and the thermal treatment in different atmospheres. In addition, the optical properties were investigated by UV-Vis absorption spectroscopy and photoluminescence spectroscopy. The results revealed that the band gap of the samples depends on the variation of diameter and sodium content caused by ion exchange and thermal treatment. Furthermore, the luminescence strongly depended on vacancies, evidenced mainly by the calcined erbium titanate nanotubes in argon atmosphere. The presence of these vacancies was confirmed by the determination of Urbach energy. The results suggest the use of thermal treated erbium titanate nanotubes in argon atmosphere in optoelectronics and photonics applications, such as photoluminescent devices, displays, and lasers.

Alcohol use, abuse, and addiction, and resulting health hazards are highly sex-dependent with unknown mechanisms. Previously, strong links between the SMPD3 gene and its coded protein neutral sphingomyelinase 2 (NSM) and alcohol abuse, emotional behavior, and bone defects were discovered and multiple mechanisms were identified for females. Here we report strong sex-dimorphisms for central, but not for peripheral mechanisms of NSM action in mouse models. Reduced NSM activity resulted in enhanced alcohol consumption in males, but delayed conditioned rewarding effects. It enhanced the acute dopamine response to alcohol, but decreased monoaminergic systems adaptations to chronic alcohol. Reduced NSM activity increased depression- and anxiety-like behavior, but was not involved in alcohol use for the self-management of the emotional state. Constitutively reduced NSM activity impaired structural development in the brain and enhanced lipidomic sensitivity to chronic alcohol. While the central effects were mostly opposite to NSM function in females, similar roles in bone-mediated osteocalcin release and its effects on alcohol drinking and emotional behavior were observed. These findings support the view that the NSM and multiple downstream mechanism may be a source of the sex-differences in alcohol use and emotional behavior., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Determining the amount of medication used is essential for correctly managing treatment systems. The unauthorized use of drugs and the importance of determining the absorbed and required dose of drugs in target organs are essential factors that justify the design of new drug monitoring systems. Electrochemical sensors and biosensors based on nanomaterials have been developed for drug monitoring in the past few years. The use of nanomaterials to optimize the analyte detection process and facilitate electron transfer in electrochemical processes has enhanced intermolecular interactions and increased diagnostic sensitivity. Considering this review, in the first part, the evaluation of cancer drugs is examined, which can be used to determine the exact dose of the drug required in different stages of cancer. Accurate monitoring of cancer drugs can increase patient life expectancy, reduce side effects, and increase economic savings. In the next section, sensors and biosensors designed for antibiotics are examined. Accurate measurement of antibiotics for determining the effectiveness of the dose in controlling infections and preventing antibiotic resistance is possible with the help of these drug diagnostic platforms. In the next part, the diagnosis of different hormones is considered. Abnormal amounts (low/high) of hormones cause multiple physiological complications and various disabilities. Therefore, accurate determination of hormone levels can effectively treat hormonal changes. In the last section, other drugs, including drugs and analgesics for which the use of electrochemical diagnostic platforms can significantly help drug distribution and social health systems, are also discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Amazonian mammal diversity is exceptionally high, yet new taxonomic discoveries continue to be made and many questions remain for understanding its diversification through time and space. Here we investigate the diversification of spiny rats in the genus Makalata, whose species are strongly associated with seasonally flooded forests, watercourses and flooded islands. We use a biogeographical approach based on a mitochondrial cytochrome b gene through divergence time estimation and reconstruction of ancestral areas and events. Our findings indicate an ancient origin of Makalata for the Guiana Shield and Eastern Amazonia as ancestral area. A first cladogenetic event led to a phylogeographic break into two broader clades of Makalata through dispersal, implying a pattern of western/Eastern Amazonian clades coinciding with the Purus Arch (middle Miocene). Most of subclades we infer originated between the late Pliocene to the early Pleistocene, with few recent exceptions in the early Pliocene through dispersal and vicariant events. The hypothesis of rivers as dispersal barriers is not corroborated for Makalata, as expected for mammalian species associated with seasonally flooded environments. We identify two key events for the expansion and diversification of Makalata species: the presence of geologically stable areas in the Guiana and Brazilian shields and the transition from lacustrine conditions in western Amazonia (Acre system) to a river system, with the establishment of the Amazon River transcontinental system and its tributaries. Our results are congruent with older geological scenarios for the Amazon basin formation (Miocene), but we do not discard the influence of recent dynamics on some speciation events and, mainly, on phylogeographic structuring processes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Miranda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Several forest types compose the apparently homogenous forest landscape of the lowland Amazon. The seasonally flooded forests ( igapós ) of the narrow floodplains of the blackwater rivers of the Amazon basin support their community of animals; however, these animals are required to adapt to survive in this environment. Furthermore, several taxa are an important source of seasonal resources for the animals in the adjacent unflooded forest ( terra firme ). During the low-water phase, the igapó becomes available to terrestrial species that make use of terra firme and igapó forests. Nonetheless, these lateral movements of terrestrial mammals between hydrologically distinct forest types remain poorly understood. This study tested the hypothesis that the attributes of the assemblages (abundance, richness, evenness, and functional groups) of the terrestrial mammals in both these forest types of the Cuieiras River basin, which is located in the Central Amazon, are distinct and arise from the ecological heterogeneity induced by seasonal floods. After a sampling effort of 10,743 camera trap days over four campaigns, two for the terra firme (6,013 trap days) and two for the igapó forests (4,730 trap days), a total of 31 mammal species (five were considered eventual) were recorded in both forest types. The species richness was similar in the igapó and terra firme forests, and the species abundance and biomass were greater in the terra firme forest, which were probably due to its higher primary productivity; whereas the evenness was increased in the igapós when compared to the terra firme forest. Although both forest types shared 84% of the species, generally a marked difference was observed in the composition of the terrestrial mammal species. These differences were associated with abundances of some specific functional groups, i.e ., frugivores/granivores. Within-group variation was explained by balanced variation in abundance and turnover, which the individuals of a given species at one site were substituted by an equivalent number of individuals of a different species at another site. However, the occupancy was similar between both forest types for some groups such as carnivores. These findings indicate that seasonal flooding is a relevant factor in structuring the composition of terrestrial mammal assemblages between terra firme and floodplain forests, even in nutrient-poor habitats such as igapós . The results also highlight the importance of maintaining the mosaic of natural habitats on the scale of the entire landscape, with major drainage basins representing management units that provide sufficiently large areas to support a range of ecological processes ( e.g ., nutrient transport, lateral movements and the persistence of apex predators)., Competing Interests: The authors declare that they have no competing interests., (© 2022 Gonçalves et al.)

Understanding the distribution patterns of threatened species is central to conservation. The Amazonian distribution of the northern tiger cat (N-tiger cat, Leopardus tigrinus) and its interspecific relationship with the ocelot, its potential intraguild killer, are intriguing. Here, we combined presence/absence records with species distribution models (SDMs) to determine N-tiger cat occurrence in the Amazon. We also modeled ocelot density from 46 published estimates. The N-tiger cat's presence in the Amazon was negatively influenced by ocelot density and net primary productivity and positively influenced by savannas and precipitation in the driest month. The best-fitting model predicted highly patchy N-tiger cat occurrence over an area of 236,238.67 km 2 , almost exclusively in savanna enclaves. Additionally, 312,348 camera trap-days at 49 sites in the Amazon revealed no N-tiger cats. The ocelot densities were significantly higher in areas with denser vegetation cover and warmer habitats, with predicted densities ≥ 0.6 ind/km 2 throughout most of the biome. The lowest ocelot densities (≤ 0.06 ind/km 2 ) were observed along the predicted range of N-tiger cats. Our findings highlight that the N-tiger cat's presence in the Amazon is restricted to savannas and highly influenced by ocelot density, emphasizing the importance of including species interactions in SDMs., (© 2022. The Author(s).)

Our study compared brain MRI with neuropathological findings in patients with primary age-related tauopathy (PART) and Alzheimer's disease (AD), while assessing the relationship between brain atrophy and clinical impairment. We analyzed 233 participants: 32 with no plaques ("definite" PART-BRAAK stage higher than 0 and CERAD 0), and 201 cases within the AD spectrum, with 25 with sparse (CERAD 1), 76 with moderate (CERAD 2), and 100 with severe (CERAD 3) degrees of neuritic plaques. Upon correcting for age, sex, and age difference at MRI and death, there were significantly higher levels of atrophy in CERAD 3 compared to CERAD 1-2 and a trend compared to PART (p = 0.06). In the anterior temporal region, there was a trend for higher levels of atrophy in PART compared to Alzheimer's disease spectrum cases with CERAD 1 (p = 0.08). We then assessed the correlation between regional brain atrophy and CDR sum of boxes score for PART and AD, and found that overall cognition deficits are directly correlated with regional atrophy in the AD continuum, but not in definite PART. We further observed correlations between regional brain atrophy with multiple neuropsychological metrics in AD, with PART showing specific correlations between language deficits and anterior temporal atrophy. Overall, these findings support PART as an independent pathologic process from AD., (Copyright © 2022. Published by Elsevier Inc.)

Background: Puberty is a period of intense changes in human body and, additionally, participation in sports is viewed as prominent form of physical activity among male adolescent athletes. The current study was aimed to examine the intra-individual changes in body composition and bone tissue during years of maximal growth and the effect of 12-month participation in sports contrasting in mechanical impact., Methods: The sample included 40 male adolescent athletes (soccer: n = 20; swimming: n = 20) aged 12.57 ± 0.37 years who were followed for 12 months. Stature and body mass were measured, bone mineral content (BMC), areal bone mineral density (aBMD), lean soft and fat tissues assessed using DXA. Food intake was estimated using a questionnaires and training sessions individually monitored. Repeated measures ANOVA tested the differences between sports and 12-month intra-individual variation (time moments: TM1, TM2). The analyses on aBMD for total body and total body less head were repeated controlling for variation in stature at baseline., Results: Soccer players completed 63 ± 31 sessions (95 ± 47 h). Respective values for swimmers were 248 ± 28 sessions and 390 ± 56 h. In general, the analysis of aBMD as dependent variable evidenced significant effect of sport-associated variation (F = 5.254, p < 0.01; η 2  = 0.35) and 12-month increments, particularly at lower limbs (F = 97.238, p < 0.01; η 2  = 0.85). Respective mean values for aBMD were SCC TM1  = 0.885 g.cm -2 , SWM TM1  = 0.847 g.cm -2 , SCC TM2  = 0.939 g.cm -2 , SWM TM2  = 0.880. Regarding the lean soft tissue, the magnitude of effects was very large for intra-individual variation (F = 223.043, p < 0.01; η 2  = 0.92) and moderate between sports (F = 7.850, p < 0.01; η 2  = 0.41): SCC TM1  = 30.6 kg, SWM TM1  = 34.9 kg, SCC TM2  = 35.8 kg, SWM TM2  = 40.5 kg). Finally, d-cohen values reporting percentage of intra-individual changes in aBMD between soccer players ad swimmers were large for the trochanter (d = 1.2; annual increments: SCC = 8.1%, SWM = 3.6%)., Conclusion: Puberty appeared as a period of significant intra-individual changes in lean soft tissue and bone mineral density. With increasing accumulated training experience, mean difference between sports contrasting in mechanical impact tended to me more pronounced in particular at the lower limbs., (© 2022. The Author(s).)

Apolipoprotein E ε4 (APOE4) is the primary genetic risk factor for the late-onset form of Alzheimer's disease (AD). Although the reason for this association is not completely understood, researchers have uncovered numerous effects of APOE4 expression on AD-relevant brain processes, including amyloid beta (Aβ) accumulation, lipid metabolism, endosomal-lysosomal trafficking, and bioenergetics. In this study, we aimed to determine the effect of APOE4 allelic dosage on regional brain lipid composition in aged mice, as well as in cultured neurons. We performed a targeted lipidomic analysis on an AD-vulnerable brain region (entorhinal cortex; EC) and an AD-resistant brain region (primary visual cortex; PVC) from 14-15 month-old APOE3/3, APOE3/4, and APOE4/4 targeted replacement mice, as well as on neurons cultured with conditioned media from APOE3/3 or APOE4/4 astrocytes. Our results reveal that the EC possesses increased susceptibility to APOE4-associated lipid alterations compared to the PVC. In the EC, APOE4 expression showed a dominant effect in decreasing diacylglycerol (DAG) levels, and a semi-dominant, additive effect in the upregulation of multiple ceramide, glycosylated sphingolipid, and bis(monoacylglycerol)phosphate (BMP) species, lipids known to accumulate as a result of endosomal-lysosomal dysfunction. Neurons treated with conditioned media from APOE4/4 vs. APOE3/3 astrocytes showed similar alterations of DAG and BMP species to those observed in the mouse EC. Our results suggest that APOE4 expression differentially modulates regional neuronal lipid signatures, which may underlie the increased susceptibility of EC-localized neurons to AD pathology., (© 2022. The Author(s).)

Background: The classification of health problems of persons with Mucopolysaccharidosis (MPS) based on the International Classification of Functioning, Disability and Health (ICF) may contribute to better understanding the disease impacts. The ICF is a useful tool to describe disabilities and functioning, especially in diseases with multisystemic involvement., Aim: To identify and classify the health needs of persons with non-neuronopathic MPS according to the ICF., Design: A cross-sectional study., Setting: Department of Physical Therapy (Federal University, Brazil)., Population: Persons with non-neuronopathic MPS., Methods: Semi-structured interviews covering all components of the ICF were conducted to know the patients' perspectives of their health problems (patient-reported outcomes). The speeches were transcribed verbatim and analyzed by researchers to identifying meaningful concepts. Then, the concept units were linked to ICF components and the magnitude of the problem to ICF qualifiers. Data are shown by descriptive statistics and separated into two groups: children and adolescents, and adults., Results: A total of 60 different ICF categories were used to classify participants' functioning. A total of 28 and 51 categories was necessary to classify the health problems of children and adults, respectively. Additionally, 16 categories related to contextual factors were used, of which eight and 12 were identified as facilitators by children, adolescents, and adults, respectively. The main problems were related to supportive functioning of arms or legs (b7603), pain in the body part (b2801), respiratory functions (b440), and voice functions (b310). Limitations in the activity and participation component were related to walking (d450), fine hand use (d440), washing oneself (d510), and dressing (d540). Recreation and leisure (d920) was restricted to approximately half of the studied population., Conclusions: People with MPS face impairments of body structures and functions, activity limitations and restrictions to participation. Environmental factors may be act as facilitators of these problems., Clinical Rehabilitation Impact: The ICF is a useful tool to classify the health problems of people with non-neuropathic MPS. The planning of rehabilitation programs needs to covers all components of functioning to provide a biopsychosocial model of care. The ICF categories may direct health professionals to more effective targets.

Introduction  Idiopathic sudden sensorineural hearing loss (ISSHL) is a disabling otologic urgency whose ethiopathogenesis is still controversial. Only in recent years metabolic syndrome (MetS) has been implicated as a possible aggravating factor in the prognosis of recovery from ISSHL. Objective  To assess whether the preexistence of MetS interferes on hearing recovery levels. Methods  Retrospective cohort study composed of adult (> 18 years old) ISSHL patients admitted for treatment between January 2015 and December 2019. To diagnose ISSHL, we used pure-tone audiometry, and identified MetS patients based on the criteria of the United States National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III). The treatment protocol comprised hospitalization for five days for the intravenous administration of dexamethasone, audiometric surveillance, imaging and blood analyses, and, based on recovery, the planning of rescue treatments (intratympanic administration of dexamethasone and/or hyperbaric oxygen). The Siegel criteria were used to evaluate the hearing outcomes. Results  The final sample was composed of 81 patients, 48 without MetS (nMetS) and 33 with MetS. Regarding the Siegel recovery category, the nMetS group had significantly better results ( p  = 0.001), with 44% of complete recoveries against 6% in the MetS, and 58% of the MetS patients had the worst outcome, contrasting with 27% in the nMetS group. The nMetS group had an overall better evolution in terms of hearing recovery and had a significant improvement in the median hearing gain (20.6 dB versus 8.8 dB; p  = 0.008). Additionally, the multivariate analysis revealed that the presence of MetS is a significant risk factor for a worse outcome (odds ratio [OR] = 0.30; 95% confidence interval [95%CI] = 0.10-0.85). Conclusion  Regardless of age, gender, the initial audiometry threshold, and autoimmunity, MetS is a clear risk factor for a worse outcome regarding the recovery of hearing after ISSHL., Competing Interests: Conflict of Interests The authors have no conflict of interests to declare., (Fundação Otorrinolaringologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Titanium nanotubes have attractive morphological and physicochemical properties for several applications, such as high surface area, mesoporous structure, good stability, ion exchange capacity, and antibacterial property. Therefore, the field of nanotube applications is increasingly expanding, such as in solar cells sensitized by dye, photocatalysis, and antibacterial activity, among others. Therefore, a study of the antibacterial properties of sodium titanate nanotubes (Na-TiNTs) was carried out together with physicochemical characterizations, such as Raman spectroscopy which shows a peak characteristic of Na-O-Ti from nanotube-agglomerated regions. The XRD diffractogram confirmed the Raman spectra and evidenced the crystalline structure associated to Na-TiNT, which showed the characteristic peaks of the sodium trititanate crystal. SEM and TEM images showed the morphology of hollow nanotubes and forming semispherical particles. EDS shows the percentage values of each of the compounds in the Na-TiNT. The bacterial activity of the Na-TiNT was analyzed in Escherichia coli , Staphylococcus aureus , and Pseudomonas aeruginosa . Na-TiNT modified the activity of the gentamicin and norfloxacin antibiotics against multiresistant strains. Synergistic effects against Gram-positive S. aureus 10 and Gram-negative P. aeruginosa 15 bacteria were observed when the Na-TiNT was associated with gentamicin, reducing the concentration of this antibiotic that is required to inhibit bacterial growth. Another synergic effect was observed for S. aureus 10 with norfloxacin., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Enzo V. H. Agressott et al.)

A maturity-associated gradient among adolescent athletes in many sports tends to favour early maturing participants. This study was aimed to describe inter-individual variance in growth and skeletal maturation among male youth table tennis. The sample included 99 players registered in competitive clubs for at least 2 years. Chronological age (CA) ranged 10.00-14.63 years. Stature and body mass were plotted relative to US references. Skeletal age (SA) was estimated with the Fels method. Maturity status was given as SA minus CA. Somatic maturation was derived from predicted age at peak height velocity. Mean values for stature and weight were above the reference medians from 10 to 13 years and at the median in the oldest group. In general, SA was in advance to CA (CA: 12.45 ± 1.28 years; SA: 13.44 ± 2.37 years). The majority of the players were early maturing according to SA (52%) and average maturing based on the somatic indicator (80%). The results suggested that table tennis tends to retain taller and heavier participants who are somewhat advanced in skeletal maturity. Participation in youth table tennis and opportunities to win need to consider age- and maturity-associated variations, particularly regarding bands for competitions.

Objective: The purpose of the study was to evaluate the agreement between the Fels and Greulich-Pyle methods for the assessment of skeletal age (SA) in female youth soccer players., Methods: The sample included 441 Portuguese players 10.08-16.73 years of age who regularly participated in organized and competitive soccer. Standardized radiographs of the left hand-wrist were obtained and analyzed by an experienced examiner. SA was estimated with the Fels and Greulich-Pyle (GP) methods. Differences between SA and chronological age (CA) were used to define skeletal maturity groups: late, average and early maturing. In addition to descriptive statistics, Cohen's kappa and Lin concordance correlation coefficients were used to evaluate agreement between methods., Results: Intraindividual differences in SA based on the two methods varied between 0.10 to 1.47 years among age groups with larger mean differences at older ages. Agreement of maturity classifications between methods was 74% at younger ages (under-13: kappa = 0.48; under-14: kappa = 0.39; Lin CCC = 0.68) and declined with increasing CA (under-17: 19% agreement; kappa = 0.001; Lin CCC = 0.11). About 19% of the total sample was skeletally mature with the Fels method and an SA was not assigned; in contrast, no players were skeletally mature with the GP method., Conclusions: GP SAs were systematically lower than Fels SAs among female soccer players. Intraindividual variability in SAs between methods was considerable. The findings highlight the impact of method on estimates of maturity status., (© 2021 Wiley Periodicals LLC.)

Mental disorders are highly comorbid and occur together with physical diseases, which are often considered to arise from separate pathogenic pathways. We observed in alcohol-dependent patients increased serum activity of neutral sphingomyelinase. A genetic association analysis in 456,693 volunteers found associations of haplotypes of SMPD3 coding for NSM-2 (NSM) with alcohol consumption, but also with affective state, and bone mineralisation. Functional analysis in mice showed that NSM controls alcohol consumption, affective behaviour, and their interaction by regulating hippocampal volume, cortical connectivity, and monoaminergic responses. Furthermore, NSM controlled bone-brain communication by enhancing osteocalcin signalling, which can independently supress alcohol consumption and reduce depressive behaviour. Altogether, we identified a single gene source for multiple pathways originating in the brain and bone, which interlink disorders of a mental-physical co-morbidity trias of alcohol abuse-depression/anxiety-bone disorder. Targeting NSM and osteocalcin signalling may, thus, provide a new systems approach in the treatment of a mental-physical co-morbidity trias., (© 2021. The Author(s).)

Surgical intervention is necessary following nerve trauma. Tubular prostheses can guide growing axons and inserting substances within these prostheses can be positive for the regeneration, making it an alternative for the current standard tools for nerve repair. Our aim was to investigate the effects of fibrin glue BthTL when combined with a synthetic TNF mimetic-action peptide on nerve regeneration. Male Wistar rats suffered left sciatic nerve transection. For repairing, we used empty silicon tubes (n = 10), tubes filled with fibrin glue BthTL (Tube + Glue group, n = 10) or tubes filled with fibrin glue BThTL mixed with TNF mimetic peptide (Tube + Glue + Pep group, n = 10). Animals were euthanized after 45 days. We collected nerves to perform immunostaining (neurofilament, GAP43, S100-β, NGFRp75 and Iba-1), light and transmission electron microscopy (for counting myelinated, unmyelinated and degenerated fibers; and for the evaluation of morphometric aspects of regenerated fibers) and collagen staining. All procedures were approved by local ethics committee (protocol 063/17). Tube + Glue + Pep group showed intense inflammatory infiltrate, higher Iba-1 expression, increased immunostaining for NGFRp75 receptor (which characterizes Schwann cell regenerative phenotype), higher myelin thickness and fiber diameter and more type III collagen deposition. Tube + Glue group showed intermediate results between empty tube and Tube + Glue + Pep groups for anti-NGFRp75 immunostaining, inflammation and collagen; on fiber counts, this group showed more degenerate fibers and fewer unmyelinated axons than others. Empty tube group showed superiority only in GAP43 immunostaining. A combination of BthTL glue and TNF mimetic peptide induced greater axonal regrowth and remyelination., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Intracerebral hemorrhage (ICH) recurrence risk is known to be higher in patients with cerebral amyloid angiopathy (CAA) as compared to other causes of ICH. Risk factors for ICH recurrence are not completely understood, and our goal was to study specific imaging microangiopathy markers., Methods: Retrospective case-control study of patients with non-traumatic ICH admitted to a single center between 2014 and 2017 who underwent magnetic resonance imaging (MRI). Clinical characteristics of the index event and occurrence of death and ICH recurrence were collected from clinical records. MRI images were independently reviewed by 2 neuroradiologists. Groups of patients with CAA-related and CAA-unrelated ICH defined were compared. Presence of CAA was defined according to the Boston modified criteria. Survival analysis with Kaplan-Meier curves and Cox-regression analyses was performed to analyze ICH recurrence-free survival., Results: Among 448 consecutive patients with non-traumatic ICH admitted during the study period, 104 were included in the study, mean age 64 years (±13.5), median follow-up of 27 months (interquartile range, IQR 16-43), corresponding to 272 person-years of total follow-up. CAA-related ICH patients presented higher burden of lobar microbleeds (p < 0.001), higher burden of enlarged perivascular spaces (EPVS) in centrum semiovale (p < 0.001) and more frequently presented cortical superficial siderosis (cSS; p < 0.001). ICH recurrence in patients with CAA was 12.7 per 100 person-years, and no recurrence was observed in patients without CAA. Variables associated with ICH recurrence in the whole population were age (hazard ratio [HR] per 1-year increment = 1.05, 95% CI 1.00-1.11, p = 0.046), presence of disseminated cSS (HR 3.32, 95% CI 1.09-10.15, p = 0.035) and burden of EPVS in the centrum semiovale (HR per 1-point increment = 1.80, 95% CI 1.04-3.12, p = 0.035)., Conclusions: This study confirms a higher ICH recurrence risk in patients with CAA-related ICH and suggests that age, disseminated cSS, and burden of EPVS in the centrum semiovale are associated with ICH recurrence., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Background: Skeletal age (SA) is considered the best method of assessing biological maturation. The aim of this study was to determine intra-observer (reproducibility) and inter-observer agreement of SA values obtained via the Greulich-Pyle (GP) method. In addition, the variation in calculated SAs by alternative GP protocols was examined., Methods: The sample was composed of 100 Portuguese female soccer players aged 12.0-16.7 years. SAs were determined using the GP method by two observers (OB1: experience < 100 exams using GP; OB2: experience > 2000 exams using several methods). The radiographs were examined using alternative GP protocols: (wholeGP) the plate was matched to the atlas as an overall approach; (30-boneGP) bone-by-bone inspections of 30-bones; (GPpmb) bone-by-bone inspections of the pre-mature bones only. For the 30-boneGP and GPpmb approaches, SA was calculated via the mean (M) and the median (Md)., Results: Reproducibility ranged 82-100% and 88-100% for OB1 and OB2, respectively. Inter-observer agreement (100 participants multiplied by 30 bones) was 92.1%. For specific bones, agreement rates less than 90% were found for scaphoid (81%), medial phalange V (83%), trapezium (84%) and metacarpal V (87%). Differences in wholeGP SAs obtained by the two observers were moderate (d-cohen was 0.79). Mean differences between observers when using bone-by bone SAs were trivial (30-boneGP: d-cohen less than 0.05; GPpmb: d-cohen less than 0.10). The impact of using the mean or the median was negligible, particularly when analyses did not include bones scored as mature., Conclusion: The GP appeared to be a reasonably reproducible method to assess SA and inter-observer agreement was acceptable. There is evidence to support a recommendation of only scoring pre-mature bones during later adolescence. Further research is required to examine whether these findings are consistent in younger girls and in boys.

The tumor suppressor gene TP53 is the most commonly mutated gene in human cancer. In addition to loss of tumor suppressor functions, mutations in TP53 promote cancer progression by altering cellular iron acquisition and metabolism. A newly identified role for TP53 in the coordination of iron homeostasis and cancer cell survival lies in the ability for TP53 to protect against ferroptosis, a form of iron-mediated cell death. The purpose of this study was to determine the extent to which TP53 mutation status affects the cellular response to ferroptosis induction. Using H1299 cells, which are null for TP53, we generated cell lines expressing either a tetracycline inducible wild-type (WT) TP53 gene, or a representative mutated TP53 gene from six exemplary "hotspot" mutations in the DNA binding domain (R273H, R248Q, R282W, R175H, G245S, and R249S). TP53 mutants (R273H, R248Q, R175H, G245S, and R249S) exhibited increased sensitivity ferroptosis compared to cells expressing WT TP53. As iron-mediated lipid peroxidation is critical for ferroptosis induction, we hypothesized that iron acquisition pathways would be upregulated in mutant TP53-expressing cells. However, only cells expressing the R248Q, R175H, and G245S TP53 mutation types exhibited statistically significant increases in spontaneous iron regulatory protein (IRP) RNA binding activity following ferroptosis activation. Moreover, changes in the expression of downstream IRP targets were inconsistent with the observed differences in sensitivity to ferroptosis. These findings reveal that canonical iron regulatory pathways are bypassed during ferroptotic cell death. These results also indicate that induction of ferroptosis may be an effective therapeutic approach for tumor cells expressing distinct TP53 mutation types.

Soccer is the most popular sport in the world and, since it is a contact sport, players are at risk for head injury, including concussion. Here, we proposed to investigate the association of heading and concussion with macroscopic brain structure among adult amateur soccer players. For this study, 375 amateur soccer players (median age 23 years) completed HeadCount-12m to estimate heading over the 12 months prior to MRI and lifetime concussion. T1-weighted 3D magnetization prepared rapid acquisition gradient echo (MP-RAGE) MRI was performed at 3 Tesla. Parcellation was performed using Freesurfer to extract regional gray and white matter volumes as well as regional cortical thickness and total intracranial volume. Regional cortical brain volumes were normalized by total intracranial volume. We categorized heading into quartiles and concussion as 0, 1 or 2 or more. Generalized linear regressions were used to test the association of heading or concussion with each brain morphometry metric, including age and sex, as covariates. Neither heading nor concussion were associated with reduced brain volume or cortical thickness. We observed that greater heading was associated with greater gray matter volume in the left inferior parietal area, which may reflect effects related to training., Competing Interests: The authors have declared that no competing interests exist.

Phosphatidic acid (PA) is a signaling lipid involved in the modulation of synaptic structure and functioning. Based on previous work showing a decreasing PA gradient along the longitudinal axis of the rodent hippocampus, we asked whether the dorsal hippocampus (DH) and the ventral hippocampus (VH) are differentially affected by PA modulation. Here, we show that phospholipase D1 (PLD1) is a major hippocampal PA source, compared to PLD2, and that PLD1 ablation affects predominantly the lipidome of the DH. Moreover, Pld1 knockout (KO) mice show specific deficits in novel object recognition and social interaction and disruption in the DH-VH dendritic arborization differentiation in CA1/CA3 pyramidal neurons. Also, Pld1 KO animals present reduced long-term depression (LTD) induction and reduced GluN2A and SNAP-25 protein levels in the DH. Overall, we observe that PLD1-derived PA reduction leads to differential lipid signatures along the longitudinal hippocampal axis, predominantly affecting DH organization and functioning., Competing Interests: Declaration of Interests G.D.P. is a full-time employee of Denali Therapeutics. G.D.P. and T.G.O. are listed as inventors on the patent number WO2010138869A1, “Modulation of Phospholipase D for the Treatment of Neurodegenerative Disorders.” R.B.C., G.D.P., and T.G.O. are listed as inventors on the patent number US20120302604A1, “Modulation of Phospholipase D for the Treatment of the Acute and Chronic Effects of Ethanol.”, (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Sporadic Parkinson's disease (PD) patients have lower α-galactosidase A (α-GAL A) enzymatic activity and Fabry disease (FD) patients potentially carry an increased risk of PD., Objective: Determination of PD prevalence in FD and clinical, biochemical and vascular neuroimaging description of FD pedigrees with concomitant PD., Methods: Clinical screening for PD in 229 FD patients belonging to 31 families, harbouring GLA gene mutation p.F113L, and subsequent pedigree analysis. Gender-stratified comparison of FD+/PD+ patients with their family members with FD but without PD (FD+/PD-) regarding Mainz scores, plasma & leukocytes α-GAL A enzymatic activity, urinary Gb3 and plasma Lyso-Gb3, vascular brain neuroimaging., Results: Prevalence of PD in FD was 1.3% (3/229) (3% in patients aged ≥50 years). Three FD patients, one female (73 years old) (P1) and two males (60 and 65 years old) (P2 and P3), three different pedigrees, presented akinetic-rigid PD, with weak response to levodopa (16% - 36%), and dopaminergic deficiency on 18F-DOPA PET. No pathogenic mutations were found in a PD gene panel. FD+/PD+ patients had worse clinical severity of FD (above upper 75% IQR in Mainz scores), and cortico-subcortical white matter/small vessel lesions. P3 patient was under enzyme therapy, started 1 year before PD diagnosis. P2-P3 patients had higher leucocyte α-GAL A activity (2,2-3 vs.1,0 (median)(nmol/h/mg))., Conclusion: We have shown a high prevalence of PD in a late-onset phenotype of FD, presenting high cerebrovascular burden and weak response to levodopa. Further studies will untangle how much of this PD phenotype is due to Gb3 deposition versus cerebrovascular lesions in the nigro-striatal network.

Lipids play an important role in neurodegeneration, neuroinflammation, and psychiatric disorders and an imbalance in sphingolipid levels is associated with disease. Although early diagnosis and intervention of these disorders would clearly have favorable long-term outcomes, no diagnostic tests currently exist that can accurately identify people at risk. Reliable prognostic biomarkers that are easily accessible would be beneficial to determine therapy and treatment response in clinical trials. Recent advances in lipidomic investigation methods have greatly progressed the knowledge of sphingolipids in neurodegenerative and psychiatric disorders over the past decades although more longitudinal studies are needed to understand its exact role in these disorders to be used as potential tools in the clinic. In this review, we give an overview of the current knowledge of sphingolipids in neurodegenerative and psychiatric disorders and explore recent advances in investigation methods. Finally, the potential of sphingolipid metabolism products and signaling molecules as potential biomarkers for diagnosis, prognostic, or surrogate markers of treatment response is discussed., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Alzheimer disease (AD) is a neurodegenerative disorder characterized pathologically by the accumulation of amyloid-beta (Aβ) plaques and tau neurofibrillary tangles (NFTs). Recently, primary age-related tauopathy (PART) has been described as a new anatomopathological disorder where NFTs are the main feature in the absence of neuritic plaques. However, since PART has mainly been studied in post-mortem patient brains, not much is known about the clinical or neuroimaging characteristics of PART. Here, we studied the clinical brain imaging characteristics of PART focusing on neuroanatomical vulnerability by applying a previously validated multiregion visual atrophy scale. We analysed 26 cases with confirmed PART with paired clinical magnetic resonance imaging (MRI) acquisitions. In this selected cohort we found that upon correcting for the effect of age, there is increased atrophy in the medial temporal region with increasing Braak staging (r = 0.3937, p = 0.0466). Upon controlling for Braak staging effect, predominantly two regions, anterior temporal (r = 0.3638, p = 0.0677) and medial temporal (r = 0.3836, p = 0.053), show a trend for increased atrophy with increasing age. Moreover, anterior temporal lobe atrophy was associated with decreased semantic memory/language (r = - 0.5823, p = 0.0056; and r = - 0.6371, p = 0.0019, respectively), as was medial temporal lobe atrophy (r = - 0.4445, p = 0.0435). Overall, these findings support that PART is associated with medial temporal lobe atrophy and predominantly affects semantic memory/language. These findings highlight that other factors associated with aging and beyond NFTs could be involved in PART pathophysiology.

Xenarthrans-anteaters, sloths, and armadillos-have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, 10 anteaters, and 6 sloths. Our data set includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the southern United States, Mexico, and Caribbean countries at the northern portion of the Neotropics, to the austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n = 5,941), and Cyclopes sp. have the fewest (n = 240). The armadillo species with the most data is Dasypus novemcinctus (n = 11,588), and the fewest data are recorded for Calyptophractus retusus (n = 33). With regard to sloth species, Bradypus variegatus has the most records (n = 962), and Bradypus pygmaeus has the fewest (n = 12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other data sets of Neotropical Series that will become available very soon (i.e., Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans data set. Please cite this data paper when using its data in publications. We also request that researchers and teachers inform us of how they are using these data., (© 2019 The Authors. Ecology © 2019 The Ecological Society of America.)

Lysophosphatidic acid (LPA) is an important bioactive lipid species that functions in intracellular signaling through six characterized G protein-coupled receptors (LPA 1-6 ). Among these receptors, LPA 1 is a strong candidate to mediate the central effects of LPA on emotion and may be involved in promoting normal emotional behaviors. Alterations in this receptor may induce vulnerability to stress and predispose an individual to a psychopathological disease. In fact, mice lacking the LPA 1 receptor exhibit emotional dysregulation and cognitive alterations in hippocampus-dependent tasks. Moreover, the loss of this receptor results in a phenotype of low resilience with dysfunctional coping in response to stress and induces anxiety and several behavioral and neurobiological changes that are strongly correlated with mood disorders. In fact, our group proposes that maLPA1-null mice represent an animal model of anxious depression. However, despite the key role of the LPA-LPA 1 -pathway in emotion and stress coping behaviors, the available information describing the mechanisms by which the LPA-LPA 1 -pathway regulates emotion is currently insufficient. Because activation of LPA 1 requires LPA, here, we used a Matrix-Assisted Laser Desorption/ Ionization mass spectrometry-based approach to evaluate the effects of an LPA 1 receptor deficiency on the hippocampal levels of LPA species. Additionally, the impact of stress on the LPA profile was also examined in both wild-type (WT) and the Malaga variant of LPA1-null mice (maLPA 1 -null mice). Mice lacking LPA 1 did not exhibit gross perturbations in the hippocampal LPA species, but the LPA profile was modified, showing an altered relative abundance of 18:0 LPA. Regardless of the genotype, restraint stress produced profound changes in all LPA species examined, revealing that hippocampal LPA species are a key target of stress. Finally, the relationship between the hippocampal levels of LPA species and performance in the elevated plus maze was established. To our knowledge, this study is the first to detect, identify and profile LPA species in the hippocampus of both LPA 1 -receptor null mice and WT mice at baseline and after acute stress, as well as to link these LPA species with anxiety-like behaviors. In conclusion, the hippocampal LPA species are a key target of stress and may be involved in psychopathological conditions.