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BACKGROUND: It is broadly acknowledged that children with Developmental Language Disorder (DLD) show verb-related limitations. While most previous studies have focused on tense, the mastery of lexical aspect-particularly telicity-has not been the primary focus of much research. Lexical aspect refers to whether an action has a defined endpoint (telic verbs) or not (atelic verbs). OBJECTIVE: This study investigates the effect of telicity on verb recognition in Chilean children with DLD compared to their typically developing (TD) peers using the Event-Related Potential (ERP) technique. METHOD: The research design is a mixed factorial design with between-group factors of 2 (DLD/TD) and within-group factors of 2 (telic/atelic verbs) and 2 (coherent/incoherent sentences). The participants were 36 school-aged children (18 DLD, 18 TD) aged 7 to 7 years and 11 months. The task required subjects to listen to sentences that either matched or did not match an action in a video, with sentences including telic or atelic verbs. RESULTS: The study found notable differences between groups in how they processed verbs (N400 and post-N400 components) and direct objects (N400 and P600 components). CONCLUSIONS: Children with DLD struggled to differentiate telic and atelic verbs, potentially because they employed overgeneralization strategies consistent with the Event Structural Bootstrapping model.
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Intestinal trematodes are among the most common types of parasitic worms. About 76 species belonging to 14 families have been recorded infecting humans. Infection commonly occurs when humans eat raw or undercooked foods that contain the infective metacercariae. These parasites are diverse in regard to their morphology, geographical distribution and life cycle, which make it difficult to study the parasitic diseases that they cause. Many of these intestinal trematodes have been considered as endemic parasites in the past. However, the geographical limits and the population at risk are currently expanding and changing in relation to factors such as growing international markets, improved transportation systems, new eating habits in developed countries and demographic changes. These factors make it necessary to better understand intestinal trematode infections. This chapter describes the main features of human intestinal trematodes in relation to their biology, epidemiology, host-parasite relationships, pathogenicity, clinical aspects, diagnosis, treatment and control.
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Enteropatias Parasitárias , Trematódeos , Infecções por Trematódeos , Animais , Infecções por Trematódeos/epidemiologia , Infecções por Trematódeos/parasitologia , Humanos , Enteropatias Parasitárias/parasitologia , Enteropatias Parasitárias/epidemiologia , Trematódeos/patogenicidade , Trematódeos/fisiologia , Interações Hospedeiro-Parasita , Equinostomíase/parasitologia , Equinostomíase/epidemiologia , Echinostoma/fisiologia , Echinostoma/patogenicidadeRESUMO
Proton MRS is used clinically to collect localized, quantitative metabolic data from living tissues. However, the presence of baselines in the spectra complicates accurate MRS data quantification. The occurrence of baselines is not specific to short-echo-time MRS data. In short-echo-time MRS, the baseline consists typically of a dominating macromolecular (MM) part, and can, depending on B0 shimming, poor voxel placement, and/or localization sequences, also contain broad water and lipid resonance components, indicated by broad components (BCs). In long-echo-time MRS, the MM part is usually much smaller, but BCs may still be present. The sum of MM and BCs is denoted by the baseline. Many algorithms have been proposed over the years to tackle these artefacts. A first approach is to identify the baseline itself in a preprocessing step, and a second approach is to model the baseline in the quantification of the MRS data themselves. This paper gives an overview of baseline handling algorithms and also proposes a new algorithm for baseline correction. A subset of suitable baseline removal algorithms were tested on in vivo MRSI data (semi-LASER at TE = 40 ms) and compared with the new algorithm. The baselines in all datasets were removed using the different methods and subsequently fitted using spectrIm-QMRS with a TDFDFit fitting model that contained only a metabolite basis set and lacked a baseline model. The same spectra were also fitted using a spectrIm-QMRS model that explicitly models the metabolites and the baseline of the spectrum. The quantification results of the latter quantification were regarded as ground truth. The fit quality number (FQN) was used to assess baseline removal effectiveness, and correlations between metabolite peak areas and ground truth models were also examined. The results show a competitive performance of our new proposed algorithm, underscoring its automatic approach and efficiency. Nevertheless, none of the tested baseline correction methods achieved FQNs as good as the ground truth model. All separately applied baseline correction methods introduce a bias in the observed metabolite peak areas. We conclude that all baseline correction methods tested, when applied as a separate preprocessing step, yield poorer FQNs and biased quantification results. While they may enhance visual display, they are not advisable for use before spectral fitting.
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Animals adapt to the daily changes in their environmental conditions by means of genetically encoded circadian clocks. These clocks, found throughout the tree of life, regulate diverse biological functions, and allow periodical changes in physiology and behaviour. The molecular underpinnings of these clocks have been extensively studied across taxa, revealing a brain-based system that coordinates rhythmic activities through neuronal networks and signalling pathways. Entrainment, the alignment of internal rhythms with external cues or zeitgebers, is crucial for the adaptive value of these internal clocks. While the solar light-dark cycle is a primary zeitgeber for most animals, other relevant cues such as temperature, meal timing, predators, anxiety, fear, physical activity, and social interactions also play roles in entraining circadian clocks. The search of a detailed description of the circadian clocks is a goal for neurobiology and an area of growing societal interests. Moreover, as disruptions in circadian rhythms are implicated in various diseases, understanding the entrainment pathways contributes to developing interventions for improved wellbeing and health outcomes. This review focuses on socially relevant cues, examining their impact on animal physiology and behaviour, and explores the sensory pathways transmitting information to the central clock.
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Digenetic trematodes form a major group of human parasites, affecting a large number of humans, especially in endemic foci. Over 100 species have been reported infecting humans, including blood, lung, liver and intestinal parasites. Traditionally, trematode infections have been diagnosed by parasitological methods based on the detection and the identification of eggs in different clinical samples. However, this is complicated due to the morphological similarity between eggs of different trematode species and other factors such as lack of sensitivity or ectopic locations of the parasites. Moreover, the problem is currently aggravated by migratory flows, international travel, international trade of foods and changes in alimentary habits. Although efforts have been made for the development of immunological and molecular techniques, the detection of eggs through parasitological techniques remains as the gold standard for the diagnosis of trematodiases. In the present chapter, we review the current status of knowledge on diagnostic techniques used when examining feces, urine, and sputum and also analyze the most relevant characteristics used to identify eggs with a quick key for the identification of eggs.
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Fezes , Trematódeos , Infecções por Trematódeos , Humanos , Infecções por Trematódeos/diagnóstico , Infecções por Trematódeos/parasitologia , Animais , Fezes/parasitologia , Escarro/parasitologia , Contagem de Ovos de Parasitas/métodosRESUMO
Introduction: Olfactory dysfunction (OD) is frequent after SARS-CoV-2 infection. The aim of this study was to examine if long-term OD is common in post-COVID condition, and the relationship between olfaction, cognition, neuropsychiatric symptoms, and disease duration in these patients. Methods: This study included 121 participants with post-COVID condition and 51 healthy controls (HC). A comprehensive neuropsychological and neuropsychiatric assessment was conducted, encompassing various domains, including general cognition, processing speed, verbal fluency, attention, verbal memory, visual memory, visuoconstructive ability, visuospatial ability, abstraction, executive functions, anxious-depressive symptoms, general health perception, fatigue level, sleep quality, and olfaction. Statistical analyses were carried out to understand the relationship of OD with cognition, and its role as moderator variable. Results: In total, 25% of the post-covid patients had a reduced smell capacity, while only 9.3% of HC presented OD. Post-COVID patients had statistically significantly worse cognitive performance and clinical status than HC. Verbal fluency (AUC = 0.85, p < 0.001), and attention (AUC = 0.82, p < 0.001) were the variables that best discriminate between groups. OD seemed to be a moderator between fatigue and cognition, and between disease duration and attention (ß = -0.04; p = 0.014). Discussion: The study highlights marked cognitive and neuropsychiatric sequelae in individuals post-COVID relative to HC. Olfactory impairment exhibits correlations with both cognitive performance and general health. Olfaction emerges as a potential prognostic marker owing to its moderating influence on disease severity indicators.
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Rapid eye movement (REM) sleep has been hypothesized to promote emotional resilience, but any neuronal circuits mediating this have not been identified. We find that in mice, somatostatin (Som) neurons in the entopeduncular nucleus (EPSom)/internal globus pallidus are predominantly active during REM sleep. This unique REM activity is both necessary and sufficient for maintaining normal REM sleep. Inhibiting or exciting EPSom neurons reduced or increased REM sleep duration, respectively. Activation of the sole downstream target of EPSom neurons, Vglut2 cells in the lateral habenula (LHb), increased sleep via the ventral tegmental area (VTA). A simple chemogenetic scheme to periodically inhibit the LHb over 4 days selectively removed a significant amount of cumulative REM sleep. Chronic, but not acute, REM reduction correlated with mice becoming anxious and more sensitive to aversive stimuli. Therefore, we suggest that cumulative REM sleep, in part generated by the EP â LHb â VTA circuit identified here, could contribute to stabilizing reactions to habitual aversive stimuli.
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Ansiedade , Sono REM , Animais , Camundongos , Sono REM/fisiologia , Ansiedade/fisiopatologia , Masculino , Área Tegmentar Ventral/fisiologia , Camundongos Endogâmicos C57BL , Gânglios da Base/fisiologia , Gânglios da Base/fisiopatologia , Neurônios/fisiologia , Núcleo Entopeduncular/fisiologia , Somatostatina/metabolismo , Habenula/fisiologia , Proteína Vesicular 2 de Transporte de Glutamato/metabolismo , Proteína Vesicular 2 de Transporte de Glutamato/genéticaRESUMO
Intestinal trematodes constitute a major group of helminths that parasitize humans and animals with relevant morbidity and mortality. Despite the importance of the intestinal trematodes in medical and veterinary sciences, immunology and pathology of these helminth infections have been neglected for years. Apart from the work focused on the members of the family Echnistomatidae, there are only very isolated and sporadic studies on the representatives of other families of digeneans, which makes a compilation of all these studies necessary. In the present review, the most salient literature on the immunology and pathology of intestinal trematodes in their definitive hosts in examined. Emphasis will be placed on members of the echinostomatidae family, since it is the group in which the most work has been carried out. However, we also review the information on selected species of the families Brachylaimidae, Diplostomidae, Gymnophallidae, and Heterophyidae. For most of these families, coverage is considered under the following headings: (i) Background; (ii) Pathology of the infection; (iii) Immunology of the infection; and (iv) Human infections.
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Enteropatias Parasitárias , Trematódeos , Infecções por Trematódeos , Animais , Humanos , Trematódeos/fisiologia , Trematódeos/imunologia , Infecções por Trematódeos/parasitologia , Infecções por Trematódeos/imunologia , Infecções por Trematódeos/veterinária , Enteropatias Parasitárias/imunologia , Enteropatias Parasitárias/parasitologia , Intestinos/parasitologia , Intestinos/patologia , Intestinos/imunologia , Interações Hospedeiro-Parasita/imunologiaRESUMO
Young children's linguistic and communicative abilities are foundational for their academic achievement and overall well-being. We present the positive outcomes of a brief tablet-based intervention aimed at teaching toddlers and preschoolers new word-object and letter-sound associations. We conducted two experiments, one involving toddlers ( ~ 24 months old, n = 101) and the other with preschoolers ( ~ 42 months old, n = 152). Using a pre-post equivalent group design, we measured the children's improvements in language and communication skills resulting from the intervention. Our results showed that the intervention benefited toddlers' verbal communication and preschoolers' speech comprehension. Additionally, it encouraged vocalizations in preschoolers and enhanced long-term memory for the associations taught in the study for all participants. In summary, our study demonstrates that the use of a ludic tablet-based intervention for teaching new vocabulary and pre-reading skills can improve young children's linguistic and communicative abilities, which are essential for future development.
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Oncogene-driven expression and activation of receptor tyrosine kinases promotes tumorigenesis and contributes to drug resistance. Increased expression of the kinases discoidin domain receptor 2 (DDR2), RET Proto-Oncogene (RET), Platelet Derived Growth Factor Receptor Alpha (PDGFRA), KIT Proto-Oncogene (KIT), MET Proto-Oncogene (MET), and anaplastic lymphoma kinase (ALK) independently correlate with decreased overall survival and event free survival of pediatric neuroblastoma. The multikinase inhibitor sitravatinib targets DDR2, RET, PDGFRA, KIT, and MET with low nanomolar activity and we therefore tested its efficacy against orthotopic and syngeneic tumor models. Sitravatinib markedly reduced cell proliferation and migration in vitro independently of N-Myc proto-oncogene (MYCN), ALK, or c-Myc proto-oncogene status and inhibited proliferation and metastasis of human orthotopic xenografts. Oral administration of sitravatinib to homozygous Th-MYCN transgenic mice (Th-MYCN+/+) after tumor initiation completely arrested further tumor development with no mice dying of disease while maintained on sitravatinib treatment (control cohort 57 days median time to sacrifice). Among these top kinases, DDR2 expression has the strongest correlation with poor survival and high stage at diagnosis and the highest sensitivity to the drug. We confirmed on-target inhibition of collagen-mediated activation of DDR2. Genetic knockdown of DDR2 partially phenocopies sitravatinib treatment, limiting tumor development and metastasis across tumor models. Analysis of single-cell sequencing data demonstrated that DDR2 is restricted to mesenchymal-type tumor subpopulations and is enriched in Schwann cell precursor subpopulations found in high-risk disease. These data define an unsuspected role for sitravatinib as a therapeutic agent in neuroblastoma and reveal a novel function for DDR2 as a driver of tumor growth and metastasis.
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Receptor com Domínio Discoidina 2 , Neuroblastoma , Proto-Oncogene Mas , Transdução de Sinais , Neuroblastoma/patologia , Neuroblastoma/metabolismo , Neuroblastoma/genética , Neuroblastoma/tratamento farmacológico , Animais , Humanos , Camundongos , Receptor com Domínio Discoidina 2/metabolismo , Receptor com Domínio Discoidina 2/genética , Metástase Neoplásica , Proliferação de Células , Ensaios Antitumorais Modelo de Xenoenxerto , Linhagem Celular Tumoral , Camundongos Transgênicos , FemininoRESUMO
OBJECTIVE: Mycobacterium avium complex (MAC) and Mycobacterium abscessus are a group of nontuberculous mycobacteria (NTM) that have been described as human pathogens. Their ability to develop biofilms in tissues and medical devices is one of the most important pathogenicity factors, with important implications in diagnosis and treatment. Macrolides are usually considered one of the bases of this treatment. METHODS: Here we have studied the biofilm prevention concentration (BPC) of 16 strains (n=16) with clarithromycin to avoid the biofilm development by these NTM. RESULTS: In this study, all M. abscessus strains have similar BPC, while MAC strains showed different values. For MAC the concentrations ranged between 1-16 mg/L, while for M. abscessus the concentration was 32 mg/L for all strains except one that was 64 mg/L. CONCLUSIONS: These results open the possibility of using macrolides for the prevention of biofilm development in patients with a risk of developing NTM disease.
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Antibacterianos , Biofilmes , Claritromicina , Testes de Sensibilidade Microbiana , Micobactérias não Tuberculosas , Claritromicina/farmacologia , Biofilmes/efeitos dos fármacos , Antibacterianos/farmacologia , Micobactérias não Tuberculosas/efeitos dos fármacos , Humanos , Infecções por Mycobacterium não Tuberculosas/microbiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/prevenção & controle , Complexo Mycobacterium avium/efeitos dos fármacos , Mycobacterium abscessus/efeitos dos fármacosRESUMO
INTRODUCTION: Diabetes is associated with a number of complications, particularly if glycaemic targets are not achieved. Glycaemic control is highly linked to treatment persistence and adherence. To understand the burden of poor persistence and adherence, this systematic literature review identified existing evidence regarding basal insulin adherence/non-adherence and persistence/non-persistence among people with diabetes in Western Europe (defined as the UK, France, Spain, Switzerland, the Netherlands, Ireland, Austria, Portugal, Denmark, Norway, Sweden, Finland, Italy, Germany, Iceland and Belgium). METHODS: Eligible studies were systematically identified from two databases, Medline and Embase (published between 2012 and June 2022). Conference abstracts from ISPOR and EASD were manually included. Identified studies were screened by two independent reviewers in a two-step blinded process. The eligibility of studies was decided on the basis of pre-established criteria. A proportional meta-analysis and comparative narrative analyses were conducted to analyse the included studies. RESULTS: Twelve studies were identified. Proportions of adherence/non-adherence and persistence/non-persistence varied across studies. Pooled rates of non-persistence at 6, 12 and 18 months were 20.3% (95% CI 13.8; 27.8), 33.8% (95% CI 24.1; 44.3) and 36.5% (95% CI 33.6; 39.4), respectively. In the literature, the proportion of adherent people ranged from 41% to 64% (using the outcome measure medication possession ratio (MPR) > 80%), with a pooled rate of 55.6% (95% CI 45.3; 65.6), suggesting that approximately 44% of people with type 2 diabetes (T2D) are non-adherent. CONCLUSION: The results highlight that almost half of patients with T2D in Western Europe have poor adherence to insulin therapy and, at 18 months, one in three patients do not persist on treatment. These findings call for new basal insulin therapies and diabetes management strategies that can improve treatment persistence and adherence among people with T2D.
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Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.
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Diabetes Mellitus Tipo 2 , Progressão da Doença , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Adipócitos/metabolismo , Cromatina/genética , Cromatina/metabolismo , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/genética , Diabetes Mellitus Tipo 2/classificação , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/genética , Células Endoteliais/metabolismo , Células Enteroendócrinas , Epigenômica , Predisposição Genética para Doença/genética , Ilhotas Pancreáticas/metabolismo , Herança Multifatorial/genética , Doença Arterial Periférica/complicações , Doença Arterial Periférica/genética , Análise de Célula ÚnicaRESUMO
Minimally invasive percutaneous insertion procedures are widely used techniques in medicine. Their success is highly dependent on the skills of the practitioner. This paper presents a haptic simulator for training in these procedures, whose key component is a real percutaneous insertion needle with a sensory system incorporated to track its 3D location at every instant. By means of the proposed embedded vision system, the attitude (spatial orientation) and depth of insertion of a real needle are estimated. The proposal is founded on a novel depth estimation procedure based on optical flow techniques, complemented by sensory fusion techniques with the attitude calculated with data from an Inertial Measurement Unit (IMU) sensor. This procedure allows estimating the needle attitude with an accuracy of tenths of a degree and the displacement with an accuracy of millimeters. The computational algorithm runs on an embedded computer with real-time constraints for tracking the movement of a real needle. This haptic needle location data is used to reproduce the movement of a virtual needle within a simulation app. As a fundamental result, an ergonomic and realistic training simulator has been successfully constructed for healthcare professionals to acquire the mental model and motor skills necessary to practice percutaneous procedures successfully.
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Fluxo Óptico , Humanos , Agulhas , Simulação por Computador , Movimento , Algoritmos , Interface Usuário-ComputadorRESUMO
High-risk neuroblastoma is a very aggressive pediatric cancer, accounting for ~15% of childhood cancer mortality. Therefore, novel therapeutic strategies for the treatment of neuroblastoma are urgently sought. Here, we focused on the potential implications of the Dual-specificity tYrosine-Regulated Kinase (DYRK) family and downstream signaling pathways. We used bioinformatic analysis of public datasets from neuroblastoma cohorts and cell lines to search correlations between patient survival and expression of DYRK kinases. Additionally, we performed biochemical, molecular, and cellular approaches to validate and characterize our observations, as well as an in vivo orthotopic murine model of neuroblastoma. We identified the DYRK3 kinase as a critical mediator of neuroblastoma cell proliferation and in vivo tumor growth. DYRK3 has recently emerged as a key regulator of several biomolecular condensates and has been linked to the hypoxic response of neuroblastoma cells. Our data suggest a role for DYRK3 as a regulator of the neuroblastoma-specific protein CAMKV, which is also required for neuroblastoma cell proliferation. CAMKV is a very understudied member of the Ca2+/calmodulin-dependent protein kinase family, originally described as a pseudokinase. We show that CAMKV is phosphorylated by DYRK3, and that inhibition of DYRK3 kinase activity induces CAMKV aggregation, probably mediated by its highly disordered C-terminal half. Importantly, we provide evidence that the DYRK3/CAMKV signaling module could play an important role for the function of the mitotic spindle during cell division. Our data strongly support the idea that inhibition of DYRK3 and/or CAMKV in neuroblastoma cells could constitute an innovative and highly specific intervention to fight against this dreadful cancer.
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BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and post-COVID condition can present similarities such as fatigue, brain fog, autonomic and neuropathic symptoms. METHODS: The study included 87 patients with post-COVID condition, 50 patients with ME/CFS, and 50 healthy controls (HC). The hemodynamic autonomic function was evaluated using the deep breathing technique, Valsalva maneuver, and Tilt test. The presence of autonomic and sensory small fiber neuropathy (SFN) was assessed with the Sudoscan and with heat and cold evoked potentials, respectively. Finally, a complete neuropsychological evaluation was performed. The objective of this study was to analyze and compare the autonomic and neuropathic symptoms in post-COVID condition with ME/CFS, and HC, as well as, analyze the relationship of these symptoms with cognition and fatigue. RESULTS: Statistically significant differences were found between groups in heart rate using the Kruskal-Wallis test (H), with ME/CFS group presenting the highest (H = 18.3; p ≤ .001). The Postural Orthostatic Tachycardia Syndrome (POTS), and pathological values in palms on the Sudoscan were found in 31% and 34% of ME/CFS, and 13.8% and 19.5% of post-COVID patients, respectively. Concerning evoked potentials, statistically significant differences were found in response latency to heat stimuli between groups (H = 23.6; p ≤ .01). Latency was highest in ME/CFS, and lowest in HC. Regarding cognition, lower parasympathetic activation was associated with worse cognitive performance. CONCLUSIONS: Both syndromes were characterized by inappropriate tachycardia at rest, with a high percentage of patients with POTS. The prolonged latencies for heat stimuli suggested damage to unmyelinated fibers. The higher proportion of patients with pathological results for upper extremities on the Sudoscan suggested a non-length-dependent SFN.
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COVID-19 , Síndrome de Fadiga Crônica , Síndrome da Taquicardia Postural Ortostática , Neuropatia de Pequenas Fibras , Humanos , Síndrome de Fadiga Crônica/diagnóstico , Síndrome de COVID-19 Pós-Aguda , COVID-19/complicações , Síndrome da Taquicardia Postural Ortostática/diagnósticoRESUMO
BACKGROUND AND OBJECTIVE: Multiple system atrophy is a rare and fatal neurodegenerative disorder, characterized by autonomic dysfunction in association with either parkinsonism or cerebellar signs. The pathologic hallmark is the presence of alpha-synuclein aggregates in oligodendrocytes, forming glial cytoplasmic inclusions. Clinically, it may be difficult to distinguish form other parkinsonisms or ataxias, particularly in the early stages of the disease. In this case series we aim to describe in detail the features of MSA patients. MATERIAL AND METHODS: Unified MSA Rating Scale (UMSARS) score, structural and functional imaging and cardiovascular autonomic testing, are summarized since early stages of the disease. RESULTS: UMSARS proved to be useful to perform a follow-up being longitudinal examination essential to stratify risk of poor outcome. Neuropathological diagnosis showed an overlap between parkinsonian and cerebellar subtypes, with some peculiarities that could help to distinguish from other subtypes. CONCLUSION: A better description of MSA features with standardized test confirmed by means of neuropathological studies could help to increase sensitivity.
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Doenças do Sistema Nervoso Autônomo , Atrofia de Múltiplos Sistemas , Transtornos Parkinsonianos , Humanos , Atrofia de Múltiplos Sistemas/diagnóstico , Atrofia de Múltiplos Sistemas/patologia , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , AtaxiaRESUMO
BACKGROUND: Despite the fact that prison inmates are a population at higher risk than other groups of suffering from intestinal parasite infections in relation to their living conditions, information about these diseases in prison environments is still scarce. Herein, we analyze the status of intestinal parasite infections in a Spanish prison. METHODS: A cross-sectional study involving 528 inmates was conducted from April to June 2022 among inmates at Centro Penitenciario Picassent (Valencia, Spain). Stool specimens were examined using the direct wet mount technique, the formol-ether concentration technique, and the Ziehl-Neelsen staining method. We used STATA 16.1 for data analysis. We consider a p-value less than 0.05 significant at a 95% confidence level. RESULTS: Of the 528 inmates (471 men and 57 women; a mean age of 41.94 years) enrolled in the study, 83 (15.7%) were infected. Only six species of protozoa were detected. The gut potential microeukaryotic pathobiont Blastocystis sp. was the predominant parasite, accounting for 37 (44.6%) of the infections. Gut parasite amebas (6.6%) and pathobionts (5.3%) were more prevalent than flagellates (2.3%). The prevalence of infection with pathogenic species (8.9%) was similar to that of non-pathogenic species (8.7%). Infection among men (15.2%) was higher than in women (0.6%) (p < 0.0001). In multivariate analysis, the country of birth (AOR = 0.31, 95% CI = 0.18-0.52) and the time spent in prison (AOR = 1.83, 95% CI = 1.06-3.14) were statistically significant associated to intestinal parasite infections (p < 0.0001 and p = 0.028, respectively). CONCLUSION: This study found low levels of intestinal parasite infections in the CPP which could be indicative of the implementation of sanitary measures in prison environments in Spain. The less time spent in prison favor the risk of having infection while the Spanish nationality of inmates could reduce the risk of infection. The main recommendation would be to introduce routine parasitological tests upon foreigners entering prison.
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Enteropatias Parasitárias , Prisioneiros , Masculino , Humanos , Feminino , Adulto , Espanha/epidemiologia , Estudos Transversais , Prisões , Enteropatias Parasitárias/epidemiologiaRESUMO
BACKGROUND: RUNX1 is a transcription factor and a master regulator for the specification of the hematopoietic lineage during embryogenesis and postnatal megakaryopoiesis. Mutations and rearrangements on RUNX1 are key drivers of hematological malignancies. In humans, this gene is localized to the 'Down syndrome critical region' of chromosome 21, triplication of which is necessary and sufficient for most phenotypes that characterize Trisomy 21. MAIN BODY: Individuals with Down syndrome show a higher predisposition to leukemias. Hence, RUNX1 overexpression was initially proposed as a critical player on Down syndrome-associated leukemogenesis. Less is known about the functions of RUNX1 in other tissues and organs, although growing reports show important implications in development or homeostasis of neural tissues, muscle, heart, bone, ovary, or the endothelium, among others. Even less is understood about the consequences on these tissues of RUNX1 gene dosage alterations in the context of Down syndrome. In this review, we summarize the current knowledge on RUNX1 activities outside blood/leukemia, while suggesting for the first time their potential relation to specific Trisomy 21 co-occurring conditions. CONCLUSION: Our concise review on the emerging RUNX1 roles in different tissues outside the hematopoietic context provides a number of well-funded hypotheses that will open new research avenues toward a better understanding of RUNX1-mediated transcription in health and disease, contributing to novel potential diagnostic and therapeutic strategies for Down syndrome-associated conditions.