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Objectives: Biomimetic remineralization strategies offer promising paths for managing caries- affected dentin by restoring its morphology and structural integrity. This pilot study aimed to assess the morphological and structural changes in dentin following two chemical artificial caries-affected dentin (ACAD) protocols, evaluate the effects of three biomimetic remineralization procedures (BRPs) on dentin structure, and determine the most effective ACAD-BRP combination. The BRPs studied were casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), self-assembling P11-4 (SAP-P11-4), and calcium phosphate polymer- induced liquid precursor (Ca/P-PILP). Methods: Seventy-two specimens of healthy human dentin were divided into twelve groups. Half of each group’s samples were analyzed using field-emission gun environmental scanning electron microscope/energy dispersive X-ray, while the other half were analyzed by X-ray diffraction and micro-Raman spectroscopy. Results: Results demonstrate alterations in dentin morphology and structure induced by the ACAD protocols, affirming their effectiveness in mimicking caries-affected dentin. Among the BRPs evaluated, CPP-ACP emerged as the most promising agent for promoting remineralization and restoring dentin structure. The combination of pH cycling with CPP-ACP exhibited superior efficacy in promoting dentin remineralization compared to other combinations. Conclusions: These findings highlight the potential of biomimetic remineralization strategies, particularly CPP-ACP combined with pH cycling, as effective approaches for managing caries-affected dentin and preserving dental health.

Abstract Background To report a case of IgG4-related pachymeningitis presenting with cystic lesions mimicking neurocysticercosis. Case presentation A 40-year-old female patient with tetraparesis, dysphagia and dysphonia was evaluated with clinical examination, magnetic resonance imaging, and meningeal biopsy. Magnetic resonance imaging (MRI) revealed diffuse pachymeningeal enhancement involving the cranial, cervical, thoracic, and lumbar segments with spinal cord compression and cystic lesions. CSF immunology was initially positive for cysticercus cellulosae. After disease progression a meningeal biopsy was compatible with IgG4 related disease. The patient had partial response to rituximab and needed multiple surgical procedures for spinal cord decompression and CSF shunting. Conclusions This case highlights the possibility of IgG4-related disease in patients with diffuse pachymeningitis causing spinal cord compression, even with cystic lesions on MRI. Diagnosis of IgG4-related pachymeningitis is paramount due to the possibility of treatment response to immunotherapy, particularly to anti-CD20 agents.

Background Autoimmune encephalitis (AIE) is a group of inflammatory diseases characterized by the presence of antibodies against neuronal and glial antigens, leading to subacute psychiatric symptoms, memory complaints, and movement disorders. The patients are predominantly young, and delays in treatment are associated with worse prognosis.

ABSTRACT A 34-year-old man developed severe envenomation after being bitten by a Crotalus durissus (rattlesnake), which was treated with anticrotalic serum. Three weeks later, the patient reported paresthesia and neuropathic pain in the left hand, which had progressed to all four limbs. Electroneuromyography revealed asymmetric axonal sensorimotor multiple mononeuropathy. The patient was treated with prednisone, and six months later there was significant improvement in sensorimotor conduction. This is the first reported case of multiple mononeuropathy associated with C. durissus envenomation. Post-snake envenomation peripheral neuropathy is a rare complication requiring prompt recognition and treatment to optimize nerve function and enhance patient outcomes.

Abstract Shared e-scooter systems have become an alternative for micromobility users in cities since 2017. The success of the shared e-scooter service can be related to the provision of more last-mile flexibility and convenience to users. They can also be seen as a replacement for private cars and on-demand ridesharing, especially in highly crowded urban environments. Therefore, the main objective of this research is to disclose the main characteristics that determine shared e-scooter usage and their policy implication in a medium-sized city in the North of Portugal. To meet this purpose, a survey was conducted, and statistical analyses were performed to correlate the sociodemographic characteristics of respondents with the willingness to use shared e-scooters. Results show that gender, origin of the trip, and the main mode of transport affect the usage of e-scooters, thus specific policies should be developed to decrease these inequalities. Special attention needs to be given to the creation and expansion of dedicated areas for e-scooter ridership, zoning, and some traffic calming measures to promote a safe, user-centric, and more pleasant environment for shared e-scooter riders.

Abstract Background Monogenic autoinflammatory disorders result in a diverse range of neurological symptoms in adults, often leading to diagnostic delays. Despite the significance of early detection for effective treatment, the neurological manifestations of these disorders remain inadequately recognized. Methods We conducted a systematic review searching Pubmed, Embase and Scopus for case reports and case series related to neurological manifestations in adult-onset monogenic autoinflammatory diseases. Selection criteria focused on the four most relevant adult-onset autoinflammatory diseases—deficiency of deaminase 2 (DADA2), tumor necrosis factor receptor associated periodic fever syndrome (TRAPS), cryopyrin associated periodic fever syndrome (CAPS), and familial mediterranean fever (FMF). We extracted clinical, laboratory and radiological features to propose the most common neurological phenotypes. Results From 276 records, 28 articles were included. The median patient age was 38, with neurological symptoms appearing after a median disease duration of 5 years. Headaches, cranial nerve dysfunction, seizures, and focal neurological deficits were prevalent. Predominant phenotypes included stroke for DADA2 patients, demyelinating lesions and meningitis for FMF, and meningitis for CAPS. TRAPS had insufficient data for adequate phenotype characterization. Conclusion Neurologists should be proactive in diagnosing monogenic autoinflammatory diseases in young adults showcasing clinical and laboratory indications of inflammation, especially when symptoms align with recurrent or chronic meningitis, small vessel disease strokes, and demyelinating lesions.

Objectives: To describe clinical-sociodemographic characteristics of patients with multiple sclerosis (MS) vaccinated against COVID-19, evaluating clinical worsening after vaccination and factors associated with vaccine refusal. Methods: This is a cross-sectional observational study with application of a structured form in patients with MS from Hospital Universitário Walter Cantídio addressing clinical, sociodemographic and psychological factors related to vaccination against COVID-19. Data were tabulated and described using means with standard deviation and frequency/proportion. Statistical analysis was performed adopting statistical significance of 5%. Results: Fifty-one patients (76.4% women) were evaluated, mean age 43.3 years (18-72). Of these, 29 (57%) had mild side effects and 7 had COVID-19 after vaccination. There was no significant increase in the annualized rate of relapses or expanded disability status scale. Twelve patients reported fear regarding vaccination, with intentional delay in 5 patients. The main sources of fear mentioned were social networks, television and friends/family. Conclusions: In this study, vaccination for COVID-19 in patients with multiple sclerosis proved to be safe, not leading to relapses or functional worsening after vaccination. The fear of vaccinating led to delay in some patients, and social networks were the main source of fear.

Shared e-scooters were introduced in cities as a promise to provide accessible, affordable, flexible, and sustainable mobility. However, it is still unknown if this mode can contribute to reaching sustainability and whether it is perceived by the population as enabling or hampering such endeavors. Therefore, the present research aims to further understand people's perceptions of shared e-scooters around sustainability issues, to identify the main influential factors for using and not using this mode of transport, and how regulation could affect the demand for shared e-scooter trips. For this, a Revealed Preference (RP) survey was implemented in the city of Braga, Portugal to gather information on the above-mentioned matters, and to provide guidance for future policy and transport planning. The survey results show that most users of shared e-scooters consider this mode of transport to be sustainable (98 %). Still, the perception differs among different socioeconomic groups, especially when considering the gender of respondents (ρ

Cerebrotendinous xanthomatosis (CTX) is a rare metabolic disorder caused by mutations in the CYP27A1 gene, leading to cholestanol accumulation in various tissues, including peripheral nerves. Polyneuropathy is an underrecognized feature with considerable variability in clinical presentation and neurophysiological findings in CTX. This review assesses the prevalence, clinical manifestations, and diagnostic methodologies of polyneuropathy in CTX, exploring its underlying mechanisms and potential treatment outcomes. A literature review was conducted using PubMed, Embase, and the Virtual Health Library databases with search terms related to CTX and polyneuropathy. A total of 892 articles were initially identified, with 59 selected for in-depth analysis. The review focused on studies examining peripheral nerve involvement in CTX, including nerve conduction studies, electromyography, and nerve ultrasound. Polyneuropathy in CTX was observed in 50% to 77.7% of patients across multiple case series. Neurophysiological findings varied, with reports of axonal, demyelinating, and mixed polyneuropathies. Clinical presentation included lower limb atrophy, pes cavus, and distal weakness, with sensory symptoms less frequently reported. Treatment with chenodeoxycholic acid (CDCA) showed potential in improving nerve conduction parameters, although the response was variable and dependent on the timing of intervention. Polyneuropathy in CTX presents significant diagnostic challenges due to its heterogeneous presentation and varying neurophysiological findings. Early recognition and intervention are crucial for improving patient outcomes. Peripheral nerve ultrasound is a promising diagnostic tool, complementing traditional neurophysiological assessments. Further research is needed to standardize protocols and explore the full therapeutic potential of CDCA in managing CTX-related polyneuropathy.

Objectives: To verify the association between the ABO blood type and the risk of SARS-CoV-2 infection and COVID-19 disease severity. Methods: This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), using the 2020 PRISMA Checklist and flow diagram, and articles selected for review were analyzed using the Newcastle-Ottawa Quality Rating Scale. The research question was: “Would the ABO blood group influence the risk of infection and clinical course of patients infected with SARS-CoV-2?”, The following databases were used: Embase, PubMed, Virtual Health Library (VHL), Web of Science, ScienceDirect and Scopus. The protocol for this review was registered in the Prospective Register of Systematic Reviews (PROSPERO), number CRD42021245945. Results: We found 798 articles across PubMed, Embase, Scopus, Web of Science, Science Direct and Virtual Health Library and 54 articles were included in the final analysis. Among 30 studies evaluating the risk of COVID-19 infection, 21 found significant correlations with ABO blood groups, 14 of them revealing an increased risk in blood group A and 15 studies showing a decreased risk in blood group O. Most studies found no significant correlation with disease severity or mortality. Conclusion: The qualitative assessment of available information suggests that blood group A may be a risk factor for COVID-19 infection and that blood group O may have a protective effect. We were unable to determine a clear association between the ABO blood group and mortality. These conclusions are based on highly heterogenous evidence.

Background Wyburn-Mason syndrome is a rare, non-hereditary congenital disease, belonging to the group of neurocutaneous syndromes with fewer than 100 cases reported since its first description in 1937.Case report A young adult man was initially evaluated at the age of 2 years for proptosis and progressive visual impairment of the right eye, followed by impairment in ocular abduction, adduction and elevation as well as amaurosis. MRI revealed an expansive formation centred in the right orbit compromising conal spaces with distortion of eye muscles and optic nerve. The lesion extended through the superior orbital fissure into the right cavernous sinus and to the contralateral orbit. Despite embolisation, proptosis and oedema of the periorbital tissue continued to worsen. The combination of facial, ocular and intracranial vascular malformations and the exclusion of alternative aetiologies led to a diagnosis of cerebrofacial arteriovenous metameric syndrome (CAMS) 1 (Wyburn-Mason syndrome).Discussion Important differential diagnoses are other CAMS, such as Sturge-Weber syndrome, as well as other conditions such as retinal cavernous haemangioma and vasoproliferative tumours. The optimal treatment regimen for severe cases of this syndrome is still unclear. Wyburn-Mason syndrome should be considered in patients presenting multiple arteriovenous malformations with orbital apex lesions.

Background: The occurrence of surgical site infections (SSIs) is associated with increased risk of mortality, development of other infections, and the need for reintervention, posing a significant health burden. The aim of this review was to examine the current data and guidelines around the use of antiseptic povidone‑iodine (PVP-I) for the prevention of SSIs at each stage of surgical intervention. Methods: A literature search for selected key words was performed using PubMed. Additional papers were identified based on author expertise. Results: Scientific evidence demonstrates that PVP-I can be used at every stage of surgical intervention: preoperative, intraoperative, and postoperative. PVP-I is one of the most widely used antiseptics on healthy skin and mucous membranes for preoperative surgical site preparation and is associated with a low SSI rate. For intraoperative irrigation, aqueous PVP-I is the recommended agent and has been demonstrated to decrease SSIs in a range of surgical settings, and for postoperative wound healing, there is a growing body of evidence to support the use of PVP-I. Conclusions: There is a need for more stringent study designs in clinical trials to enable meaningful comparisons between antiseptic agents, particularly for preoperative skin preparation. The use of a single agent (PVP-I) at each stage of surgical intervention could potentially provide advantages, including economic benefits, over agents that can only be used at discrete stages of the surgical procedure. Key message: Evidence supports the use of PVP-I at all stages of surgical intervention, from preoperative measures (including skin preparation, preoperative washing, and nasal decolonization) to intraoperative irrigation, through to postoperative wound management. However, there is a need for more stringent study designs in clinical trials to enable meaningful comparisons between antiseptic agents, particularly for preoperative skin preparation.

Gender dysphoria is socially more visible and discussed today, but still underdiagnosed. It refers to distress and/or impaired function caused by inconsistency between the sex assigned at birth and gender identification. Clinical manifestations are variable. Lack of training and investment in gender issues make the diagnosis and management in primary care complex, particularly in conservative and isolated communities, with poor access to information and specialized health services. We describe the diagnosis of gender dysphoria and use of a patient centered multidisciplinary and family approach in a 12-year-old rural born adolescent, assigned female at birth. Our aim is to raise awareness of early symptoms and signs of gender dysphoria and problems faced by transgender people and their families during childhood, leading to gender dysphoria, and we hope our successful approach might improve healthcare provision for these patients, particularly in rural areas.

The design of urban spaces that foster sustainable practices requires new analytical and structural approaches to spatial planning. An appropriate pedestrian network could significantly contribute to sustainable urban development goals, particularly by promoting sustainable mobility and pedestrian friendliness. With such goals, several attempts have been made to develop suitable models for pedestrian networks. However, something that is missing from the current literature is a framework that incorporates the main findings of the various studies as an integrated concise concept of the pedestrian network. To address this knowledge gap, this paper reviews studies on pedestrian networks and evaluates this concept based on the systematic 3W1H analysis method, which asks where, what, who, and how. In essence, the following questions are thus analyzed: Where is the pedestrian network located, What criteria play a role in the pedestrian network's performance, Who uses the pedestrian network, and How can the pedestrian network be analyzed? In this context, a systematic literature review is carried out by investigating studies conducted during the period 2001 to 2023 that appear in the Scopus database. The paper presents the results of the review of a selection of 67 papers dealing with pedestrian networks. Findings show that different models have been developed based on particular characteristics. Overall, researchers aimed to identify the most suitable network based on specific criteria for optimizing the walking experience in urban areas. By synthesizing the findings reported in these papers, this paper arguably contributes to a more comprehensive understanding of pedestrian networks, provides insights into the prioritization of design phases, facilitates the use of pedestrian network assessment models for future research, and creates a bigger picture for urban planners with a multidimensional view to a new sustainable urban structure.

Abstract Background Anti-NMDAR encephalitis is an emerging differential diagnosis of first episode and persistent psychosis in the psychiatric community, as clinical manifestations include psychiatric symptoms, cognitive dysfunction, seizures, decreased consciousness, and dyskinesias. This disease is associated with extreme delta brush (EDB), but the significance and temporal course of this EEG pattern still needs to be determined. Herein, we report a case of anti-NMDAR encephalitis with persistent psychosis associated with EDB occurrence on multiple occasions during a 5-year disease course. Case presentation A 15-year-old girl was diagnosed with anti-NMDAR encephalitis and treated with progressive improvement. Four years after initial manifestations, an EDB pattern was seen on electroencephalogram (EEG) without new neurological symptoms. She had residual symptoms of episodic auditory hallucinations and impulsivity. One year later, the patient had a recurrence of neurological symptoms (seizures, dyskinesias and impaired attention), persisting with EDB on EEG. Clinical symptoms and EDB resolved after second-line treatment with rituximab. Conclusion We describe the first case of persistent psychosis in anti-NMDAR encephalitis associated with extreme delta brush on multiple EEGs on prolonged follow-up. Electroencephalographic patterns such as EDB may serve as markers of residual disease activity, including psychiatric symptoms. Further studies with prolonged EEG monitoring are needed to better understand these findings.

Abstract The Geophysical and Astronomical Observatory of the University of Coimbra (OGAUC) was officially created in 2013 after merging of two historical institutions: the Astronomical Observatory and the Geophysical Institute. As a result of almost 200 years of observations and research in astronomy and geophysical sciences, the OGAUC possesses a unique and valuable collection of long‐term observational and instrumental records. These data have an indispensable value in current geophysical and climatic studies, being among the most complete and significant in Portugal and the world. The OGAUC's data collections are complemented by a vast technical‐scientific production such as reports, research memoranda, articles, books, and instruments. This archive is largely not inventoried and poorly studied (particularly concerning meteorological, geomagnetic, and seismological data). This paper highlights the importance of the OGAUC's extensive data collection and discusses the difficulties and barriers related to its inventorying, preservation, and dissemination to the scientific community, policymakers, stakeholders, and the general public.

BackgroundThe frequency of antibodies in autoimmune encephalitis (AIE) may vary in different populations, however, data from developing countries are lacking. To describe the clinical profile of AIE in Brazil, and to evaluate seasonality and predictors of AIE in adult and pediatric patients.MethodsWe evaluated patients with possible AIE from 17 centers of the Brazilian Autoimmune Encephalitis Network (BrAIN) between 2018 and 2022. CSF and serum were tested with TBAs and CBAs. Data on clinical presentation, complementary investigation, and treatment were compiled. Seasonality and predictors of AIE in adult and pediatric populations were analyzed.ResultsOf the 564 patients, 145 (25.7%) were confirmed as seropositive, 69 (12.23%) were seronegative according to Graus, and 58% received immunotherapy. The median delay to diagnosis confirmation was 5.97 ± 10.3 months. No seasonality variation was observed after 55 months of enrolment. The following antibodies were found: anti-NMDAR (n=79, 54%), anti-MOG (n=14, 9%), anti-LGI1(n=12, 8%), anti-GAD (n=11, 7%), anti-GlyR (n=7, 4%), anti-Caspr2 (n=6, 4%), anti-AMPAR (n=4, 2%), anti-GABA-BR (n=4, 2%), anti-GABA-AR (n=2, 1%), anti-IgLON5 (n=1, 1%), and others (n=5, 3%). Predictors of seropositive AIE in the pediatric population (n=42) were decreased level of consciousness (p=0.04), and chorea (p=0.002). Among adults (n=103), predictors of seropositive AIE were movement disorders (p=0.0001), seizures (p=0.0001), autonomic instability (p=0.026), and memory impairment (p=0.001).ConclusionMost common antibodies in Brazilian patients are anti-NMDAR, followed by anti-MOG and anti-LGI1. Only 26% of the possible AIE patients harbor antibodies, and 12% were seronegative AIE. Patients had a 6-month delay in diagnosis and no seasonality was found. Findings highlight the barriers to treating AIE in developing countries and indicate an opportunity for cost-effect analysis. In this scenario, some clinical manifestations help predict seropositive AIE such as decreased level of consciousness, chorea, and dystonia among children, and movement disorders and memory impairment among adults.

Abstract Introduction Long-onset COVID syndrome has been described in patients with COVID-19 infection with persistence of symptoms or development of sequelae beyond 4 weeks after the onset of acute symptoms, a medium- and long-term consequence of COVID-19. This syndrome can affect up to 32% of affected individuals, with symptoms of fatigue, dyspnea, chest pain, cognitive disorders, insomnia, and psychiatric disorders. The present study aimed to characterize and evaluate the prevalence of sleep symptoms in patients with long COVID syndrome. Methodology A total of 207 patients with post-COVID symptoms were evaluated through clinical evaluation with a neurologist and specific exams in the subgroup complaining of excessive sleepiness. Results Among 189 patients included in the long COVID sample, 48 (25.3%) had sleep-related symptoms. Insomnia was reported by 42 patients (22.2%), and excessive sleepiness (ES) was reported by 6 patients (3.17%). Four patients with ES were evaluated with polysomnography and test, multiple sleep latencies test, and actigraphic data. Two patients had a diagnosis of central hypersomnia, and one had narcolepsy. A history of steroid use was related to sleep complaints (insomnia and excessive sleepiness), whereas depression was related to excessive sleepiness. We observed a high prevalence of cognitive complaints in these patients. Conclusion Complaints related to sleep, such as insomnia and excessive sleepiness, seem to be part of the clinical post-acute syndrome (long COVID syndrome), composing part of its clinical spectrum, relating to some clinical data.

Abstract Background Turner syndrome (TS) is a rare condition associated with a completely or partially missing X chromosome that affects 1 in 2500 girls. TS increases the risk of autoimmune diseases, including Graves’ disease (GD). Moyamoya disease is a rare cerebral arteriopathy of unknown etiology characterized by progressive bilateral stenosis of the internal carotid artery and its branches. Both TS and GD have been associated with Moyamoya. Type 2 spinocerebellar ataxia (SCA2) is an autosomal dominant cerebellar ataxia caused by a CAG repeat expansion in ATXN2. We present the first case of Moyamoya syndrome in a patient with a previous diagnosis of TS and GD who tested positive for SCA2 and had imaging findings compatible with an overlap of SCA2 and Moyamoya. Case presentation A 43-year-old woman presented with mild gait imbalance for 2 years. Her family history was positive for type 2 spinocerebellar ataxia (SCA2). She had been diagnosed with Turner Syndrome (45,X) and Graves disease three years before. Brain MRI revealed bilateral frontal and parietal cystic encephalomalacia in watershed zones, atrophy of pons, middle cerebellar peduncles and cerebellum. MR angiography showed progressive stenosis of both internal carotid arteries with lenticulostriate collaterals, suggestive of Moya-Moya disease. Molecular analysis confirmed the diagnosis of SCA2. Conclusions With increased availability of tools for genetic diagnosis, physicians need to be aware of the possibility of a single patient presenting two or more rare diseases. This report underscores the modern dilemmas created by increasingly accurate imaging techniques and available and extensive genetic testing.

This Special Issue assembles papers that highlight different types of neurogenetic disorders that occur throughout human life, from childhood to adulthood, focusing on their natural history, epidemiology, diagnosis, and treatment approaches [...]

Abstract Background COVID-19 is a pandemic disease responsible for many deaths worldwide. Many neurological manifestations have been described. We report a case of normal pressure hydrocephalus (NPH) 2 months after acute COVID19 infection, in a patient without other risk factors. Case presentation A 45-year-old male patient presented an 8-month history of progressive gait disorder and cognitive impairment after being hospitalized for SARS-CoV-2 infection. Magnetic resonance imaging (MRI) was compatible with NPH. A spinal tap test was positive and there was progressive improvement after shunting, with complete resolution of symptoms. Conclusion Other infections such as syphilis, cryptococcosis and Lyme disease have been associated with NPH. Possible mechanisms for NPH after COVID include disruption of choroid plexus cells by direct viral invasion or as a result of neuroinflammation and cytokine release and hypercoagulability leading to venous congestion and abnormalities of CSF flow. Given the significance of NPH as a cause of reversible dementia, it is important to consider the possibility of a causal association with COVID19 and understand the mechanisms behind this association.

This work explores the conformational preferences and the structure-property correlations of poly(butylene 2,5-furandicarboxylate) (PBF), a longer chain analogue of the most well-known biobased polyester from the furan family, poly(ethylene 2,5-furandicarboxylate) (PEF). A thorough computational spectroscopic study–including infrared, Raman and inelastic neutron scattering spectroscopy, combined with discrete and periodic density functional theory calculations–allowed the identification of dominant structural motifs in the amorphous and crystalline regions. Discrete calculations and vibrational spectroscopy of semi-crystalline and amorphous samples strongly support the predominance of gauche, trans, gauche conformations of the butylene glycol fragment in both the crystalline and amorphous domains. In what concerns the furandicarboxylate fragment, amorphous domains are dominated by syn,syn conformations, while in the crystalline domains the anti,anti forms prevail. A possible crystalline structure–built from these conformational preferences and including a network of C-H···O hydrogen bond contacts—was optimized using periodic density functional theory. This proposed crystal structure avoids the unrealistic structural features of the previously proposed X-ray structure, provides an excellent description of the inelastic neutron scattering spectrum of the semi-crystalline form, and allows the correlation between microscopic structure and macroscopic properties of the polymer.

Cerebrotendinous Xanthomatosis represents a rare and underdiagnosed inherited neurometabolic disorder due to homozygous or compound heterozygous variants involving the CYP27A1 gene. This bile acid metabolism disorder represents a key potentially treatable neurogenetic condition due to the wide spectrum of neurological presentations in which it most commonly occurs. Cerebellar ataxia, peripheral neuropathy, spastic paraparesis, epilepsy, parkinsonism, cognitive decline, intellectual disability, and neuropsychiatric disturbances represent some of the most common neurological signs observed in this condition. Despite representing key features to increase diagnostic index suspicion, multisystemic involvement does not represent an obligatory feature and can also be under evaluated during diagnostic work-up. Chenodeoxycholic acid represents a well-known successful therapy for this inherited metabolic disease, however its unavailability in several contexts, high costs and common use in patients at late stages of disease course limit more favorable neurological outcomes for most individuals. This review article aims to discuss and highlight the most recent and updated knowledge regarding clinical, pathophysiological, neuroimaging, genetic and therapeutic aspects related to Cerebrotendinous Xanthomatosis.

Silva Nogueira - a série enquanto discurso moderno

Dystrophinopathies are muscle diseases caused by pathogenic variants in DMD, the largest gene described in humans, representing a spectrum of diseases ranging from asymptomatic creatine phosphokinase elevation to severe Duchenne muscular dystrophy (DMD). Several therapeutic strategies are currently in use or under development, each targeting different pathogenic variants. However, little is known about the genetic profiles of northeast Brazilian patients with dystrophinopathies. We describe the spectrum of pathogenic DMD variants in a single center in northeast Brazil. This is an observational, cross-sectional study carried out through molecular-genetic analysis of male patients diagnosed with dystrophinopathies using Multiplex Ligation-dependent Probe Amplification (MLPA) followed by Next-Generation Sequencing (NGS)-based strategies. A total of 94 male patients were evaluated. Deletions (43.6%) and duplications (10.6%) were the most recurring patterns of pathogenic variants. However, small variants were present in 47.1% of patients, most of them nonsense variants (27.6%). This is the largest South American single-center case series of dystrophinopathies to date. We found a higher frequency of treatment-amenable nonsense single-nucleotide variants than most previous studies. These findings may have implications for diagnostic strategies in less-known populations, as a higher frequency of nonsense variants may mean a higher possibility of treating patients with disease-modifying drugs.

Background: Congenital myopathy-13 (CMYP13), also known as Bailey-Bloch congenital myopathy and Native American myopathy (NAM), is a condition caused by biallelic missense pathogenic variants in STAC3, which encodes an important protein necessary for the excitation-relaxation coupling machinery in the muscle. Patients with biallelic pathogenic variants in STAC3 often present with congenital weakness and arthrogryposis, cleft palate, ptosis, myopathic facies, short stature, kyphoscoliosis, and susceptibility to malignant hyperthermia provoked by anesthesia. We present two unrelated cases of Bailey-Bloch congenital myopathy descendants of non-consanguineous parents, which were investigated for delayed psychomotor development and generalized weakness. To the best of our knowledge, these are the first descriptions of CMYP13 in Brazil. In both patients, we found the previously described pathogenic missense variant p.Trp284Ser in homozygosity. Conclusion: We seek to highlight the need for screening for CMYP13 in patients expressing the typical phenotype of the disease even in the absence of Lumbee Native American ancestry, and to raise awareness to possible complications like malignant hyperthermia in Bailey-Bloch congenital myopathy.

Supratentorial Lymphocytic Inflammation with Parenchymal Perivascular Enhancement Responsive to Steroids (SLIPPERS) is a rare variant of the CLIPPERS spectrum with less than ten reports published so far. There is ongoing discussion regarding whether SLIPPERS is a disease entity on its own or just an acronym encompassing many underlying diagnoses, such as sarcoidosis, vasculitis and anti-glial fibrillary acidic protein (GFAP)-associated disease. A 40-year-old woman presented with episodes of language and attention impairment. Magnetic resonance imaging (MRI) revealed T2/FLAIR hyperintense lesions in the subcortical white matter associated with a micronodular, curvilinear perivascular contrast-enhancement. Alternative diagnoses were excluded. There was a remarkable response to steroids. A relapse occurred after six years, and the biopsy showed perivascular T-cell lymphocytic infiltrate, without granulomas, vasculitis, or neoplasia. There was complete resolution of the relapse after steroids. This case represents the longest reported follow-up of a patient diagnosed with SLIPPERS, and brain biopsy after 6 years did not suggest alternative diagnoses. This report contributes to the discussion regarding the possibility that exclusive supratentorial CLIPPERS-like pathology might be an isolated disease entity, but more biopsy-proven cases with a longer follow-up are needed to support this hypothesis. Recently, GFAP astrocytopathy has been characterized and might correspond to a significant number of cases previously diagnosed as CLIPPERS or SLIPPERS.

Biallelic loss of function of IMPA1 causes autosomal recessive intellectual developmental disorder 59 (MRT59, OMIM #617323). MRT59 has been reported to present with significant intellectual disability and disruptive behavior, but little is known about the neurocognitive pattern of those patients. Thus, the aims of this study were: (1) to assess the cognitive profile of these patients, and (2) to evaluate their functional dependence levels. Eighteen adults, aged 37 to 89 years, participated in this study: nine MRT59 patients, five heterozygous carriers and four non-carrier family members. All of them were from a consanguineous family living in Northeast Brazil. All IMPA1 patients had the (c.489_493dupGGGCT) pathogenic variant in homozygosis. For cognitive assessment, the WASI battery was applied in nine MRT59 patients and compared to heterozygous carriers and non-carrier family members. Functional dependence was evaluated using the functional independence measure (FIM). Patients showed moderate to severe intellectual disability and severe functional disabilities. Heterozygous carriers did not differ from non-carriers. MRT59 patients should be followed up by health professionals in an interdisciplinary way to understand their cognitive disabilities and functional needs properly.

Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive disorder caused by pathogenic variants in CYP27A1, leading to a deficiency in sterol 27-hydroxylase. This defect results in the accumulation of cholestanol and bile alcohols in various tissues, including the brain, tendons and peripheral nerves. We conducted this review to evaluate lipid profile abnormalities in patients with CTX. A search was conducted in PubMed, Embase and the Virtual Health Library in January 2023 to evaluate studies reporting the lipid profiles of CTX patients, including the levels of cholestanol, cholesterol and other lipids. Elevated levels of cholestanol were consistently observed. Most patients presented normal or low serum cholesterol levels. A decrease in chenodeoxycholic acid (CDCA) leads to increased synthesis of cholesterol metabolites, such as bile alcohols 23S-pentol and 25-tetrol 3-glucuronide, which may serve as surrogate follow-up markers in patients with CTX. Lipid abnormalities in CTX have clinical implications. Cholestanol deposition in tissues contributes to clinical manifestations, including neurological symptoms and tendon xanthomas. Dyslipidemia and abnormal cholesterol metabolism may also contribute to the increased risk of atherosclerosis and cardiovascular complications observed in some CTX patients.

As there is a staggering increase in flooding worldwide, many countries have prioritized sustainability of their transportation sector through flood impact prediction to support the transition during flooding. As such, research regarding the flood impacts on transportation has dramatically increased in recent years. Hybrid methods play an important role in simulating the flood situation and its impacts on traffic networks. This article offers a systematic literature review of existing research which employ hybrid methods to assess the indirect impacts of flooding on transportation. In this study, 45 articles are reviewed systematically to answer 8 research questions regarding modeling the indirect impacts of flooding on transportation. The hybrid techniques observed in the existing literature are discussed and along with the main barriers to precise prediction of flooding’s indirect impacts on transportation, future research directions are also suggested.

Shared e-scooters were introduced in urban public spaces as a way to promote a modal shift from cars in short-distance trips, as well as to improve sustainability, resilience, and equity in urban transport. However, the expansion of shared e-scooter services in 2019 proved that this mode of transport, without integrated planning strategies, can bring some problems to cities, which are related to the illegal parking of e-scooters, an increase in head injuries, and the lack of population diversity among users. Regarding the latest, this research work aims at conducting a case study in the city of Braga, Portugal to reveal who the actual and potential users of shared e-scooters are and how their socioeconomic profile (e.g., gender, age, income range, literacy, occupation) and usage patterns related to the ones found in other cities. For this, a revealed preference survey was deployed on the case study site, and the respondents’ profiles were statistically correlated with the socioeconomic characteristics of the city’s general population in order to assess if this mode of transport provides an equitable service. Results show that shared e-scooters are not equally used by people of different genders, ages, and income ranges. Information on e-scooter usage inequalities across the population is useful for the city to proceed with more socially equitable mobility policies.

The effect of water on the physicochemical properties of deep eutectic solvents (DES) is a trending research topic. In this work, inelastic neutron scattering (INS) spectroscopy, was used to probe intermolecular interactions in the water-deep eutectic solvent mixtures for the cases of choline chloride (the hydrogen bond acceptor) and three different hydrogen bond donors, with different degrees of acidity: urea, glycerol and lactic acid. It was found that quenching samples in liquid nitrogen is a procedure that may retain the liquid phase morphology of DES at the low temperatures required by INS spectroscopy. The three studied systems share the preference of water molecules to bind to chloride anion, as predicted by numerous molecular dynamics simulations. Despite this similarity, the three systems present several distinct INS features upon water addition that are related to their unique properties and structure at the molecular level. In the choline chloride:urea system, water molecules promote a strengthening of hydrogen bonds with the NH and OH donors, while for the choline chloride:lactic acid system INS probed the existence of solvated DES clusters instead of specifically interfering water molecules. This study takes advantage from the unique capabilities of INS and paves the way for future studies in these systems.

This study aims to propose a method for mapping the implementation of active learning approaches by quantifying engineering teachers' self-perception. It also seeks to examine the correlations between the implementation of active learning approaches and training, as well as publications focused on active learning. To conduct the study, active learning concepts were defined, and a set of approaches were selected for consideration in the survey. A questionnaire was developed to collect data, which was completed by teachers of 246 courses from 14 engineering programs within a school of engineering. The findings revealed that only 11% of the courses studied did not implement any active learning approach. Project-Based Learning emerged as the most implemented approach, which aligns with the context of the engineering school. Additionally, positive correlations were found between training and the implementation of active learning approaches. This work makes contributions both to the theory, as it presents a way for measuring the perceived implementation of active learning approaches and the correlation with training and publications, and for institutional policy, as it shows the importance of training for that same implementation.

The SHAPE America National Physical Education Standards have long been the foundation for best practices in quality physical education. Following the 10-year cycle for revising the standards, a task force with diverse professional backgrounds convened to update the National Standards with special consideration for stakeholders who will be impacted by these changes--most notably, K-12 students. This article presents an overview of the new standards, outlining the changes and highlighting new features, including the move from five to four standards, the reconceptualization of physical literacy, and the shift to grade-span learning indicators with learning progressions. A unique feature of this overview is the inclusion of testimonials from practitioners explaining the new standards' benefits, effectiveness, and implementation, while emphasizing a holistic approach to physical education.