Frequency of Hereditary and GBA1-Related Parkinsonism in Latin America: A Systematic Review and Meta-Analysis.

BACKGROUND: Identifying hereditary parkinsonism is valuable for diagnosis, genetic counseling, patient prioritization in trials, and studying the disease for personalized therapies. However, most studies were conducted in Europeans, and limited data exist on admixed populations like those from Latin America. OBJECTIVES: This study aims to assess the frequency and distribution of genetic parkinsonism in Latin America. METHODS: We conducted a systematic review and meta-analysis of the frequency of parkinsonian syndromes associated with genetic pathogenic variants in Latin America. We defined hereditary parkinsonism as those caused by the genes outlined by the MDS Nomenclature of Genetic Movement Disorders and heterozygous carriers of GBA1 pathogenic variants. A systematic search was conducted in PubMed, Web of Science, Embase, and LILACS in August 2022. Researchers reviewed titles and abstracts, and disagreements were resolved by a third researcher. After this screening, five researchers reanalyzed the selection criteria and extracted information based on the full paper. The frequency for each parkinsonism-related gene was determined by the presence of pathogenic/likely pathogenic variants among screened patients. Cochran's Q and I2 tests were used to quantify heterogeneity. Meta-regression, publication bias tests, and sensitivity analysis regarding study quality were also used for LRRK2-, PRKN-, and GBA1-related papers. RESULTS: We included 73 studies involving 3014 screened studies from 16 countries. Among 7668 Latin American patients, pathogenic variants were found in 19 different genes. The frequency of the pathogenic variants in LRRK2 was 1.38% (95% confidence interval [CI]: 0.52-2.57), PRKN was 1.16% (95% CI: 0.08-3.05), and GBA1 was 4.17% (95% CI: 2.57-6.08). For all meta-analysis, heterogeneity was high and publication bias tests were negative, except for PRKN, which was contradictory. Information on the number of pathogenic variants in the other genes is further presented in the text. CONCLUSIONS: This study provides insights into hereditary and GBA1-related parkinsonism in Latin America. Lower GBA1 frequencies compared to European/North American cohorts may result from limited access to gene sequencing. Further research is vital for regional prevalence understanding, enabling personalized care and therapies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Parkinson's Disease Gene Screening in Familial Cases from Central and South America.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease following Alzheimer's disease. Nearly 30 causative genes have been identified for PD and related disorders. However, most of these genes were identified in European-derived families, and little is known about their role in Latin American populations. OBJECTIVES: Our goal was to assess the spectrum and frequency of pathogenic variants in known PD genes in familial PD patients from Latin America. METHODS: We selected 335 PD patients with a family history of PD from the Latin American Research Consortium on the Genetics of PD. We capture-sequenced the coding regions of 26 genes related to neurodegenerative parkinsonism. Of the 335 PD patients, 324 had sufficient sequencing coverage to be analyzed. RESULTS: We identified pathogenic variants in 41 individuals (12.7%) in FBXO7, GCH1, LRRK2, PARK7, PINK1, PLA2G6, PRKN, SNCA, and TARDBP, GBA1 risk variants in 25 individuals (7.7%), and variants of uncertain significance in another 24 individuals (7.4%) in ATP13A2, ATP1A3, DNAJC13, DNAJC6, GBA1, LRKK2, PINK1, VPS13C, and VPS35. Of the 70 unique variants identified, 19 were more frequent in Latin Americans than in any other population. CONCLUSIONS: This is the first screening of known PD genes in a large cohort of patients with familial PD from Latin America. There were substantial differences in the spectrum of variants observed in comparison to previous findings from PD families of European origin. Our data provide further evidence that differences exist between the genetic architecture of PD in Latinos and European-derived populations. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Dynamic analyses of a soft tissue-implant interface: Biological responses to immediate versus delayed dental implants.

AIM: To qualitatively and quantitatively evaluate the formation and maturation of peri-implant soft tissues around 'immediate' and 'delayed' implants. MATERIALS AND METHODS: Miniaturized titanium implants were placed in either maxillary first molar (mxM1) fresh extraction sockets or healed mxM1 sites in mice. Peri-implant soft tissues were evaluated at multiple timepoints to assess the molecular mechanisms of attachment and the efficacy of the soft tissue as a barrier. A healthy junctional epithelium (JE) served as positive control. RESULTS: No differences were observed in the rate of soft-tissue integration of immediate versus delayed implants; however, overall, mucosal integration took at least twice as long as osseointegration in this model. Qualitative assessment of Vimentin expression over the time course of soft-tissue integration indicated an initially disorganized peri-implant connective tissue envelope that gradually matured with time. Quantitative analyses showed significantly less total collagen in peri-implant connective tissues compared to connective tissue around teeth around implants. Quantitative analyses also showed a gradual increase in expression of hemidesmosomal attachment proteins in the peri-implant epithelium (PIE), which was accompanied by a significant inflammatory marker reduction. CONCLUSIONS: Within the timeframe examined, quantitative analyses showed that connective tissue maturation never reached that observed around teeth. Hemidesmosomal attachment protein expression levels were also significantly reduced compared to those in an intact JE, although quantitative analyses indicated that macrophage density in the peri-implant environment was reduced over time, suggesting an improvement in PIE barrier functions. Perhaps most unexpectedly, maturation of the peri-implant soft tissues was a significantly slower process than osseointegration.

X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson's Disease.

BACKGROUND: Sex differences in Parkinson's disease (PD) risk are well-known. However, the role of sex chromosomes in the development and progression of PD is still unclear. OBJECTIVE: The objective of this study was to perform the first X-chromosome-wide association study for PD risk in a Latin American cohort. METHODS: We used data from three admixed cohorts: (1) Latin American Research consortium on the Genetics of Parkinson's Disease (n = 1504) as discover cohort, and (2) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (3) Bambui Aging cohort (n = 1442) as replication cohorts. We also developed an X-chromosome framework specifically designed for admixed populations. RESULTS: We identified eight linkage disequilibrium regions associated with PD. We replicated one of these regions (top variant rs525496; discovery odds ratio [95% confidence interval]: 0.60 [0.478-0.77], P = 3.13 × 10-5 replication odds ratio: 0.60 [0.37-0.98], P = 0.04). rs5525496 is associated with multiple expression quantitative trait loci in brain and non-brain tissues, including RAB9B, H2BFM, TSMB15B, and GLRA4, but colocalization analysis suggests that rs5525496 may not mediate risk by expression of these genes. We also replicated a previous X-chromosome-wide association study finding (rs28602900), showing that this variant is associated with PD in non-European populations. CONCLUSIONS: Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Huntington's Disease in Chile: Epidemiological and Genetic Aspects.

INTRODUCTION: Huntington's disease (HD) is a neurodegenerative, autosomal dominant disabling condition due to an expansion of the CAG trinucleotide in the HTT gene. Motor, psychiatric, and cognitive disorders characterize it. Chilean reports on HD in the era of molecular diagnosis were wanted. METHODS: This is a retrospective analysis of a prospective cohort of patients with HD seen at the Center for Movement Disorders (CETRAM) in Chile between 2013 and 2019. Sociodemographic, genotype, and neuropsychiatric features were investigated. RESULTS: One hundred three probands with HD were identified. The majority (63.1%) were born in the metropolitan region, followed by the VIII and V regions with 8.73% and 7.76%, respectively. When pedigrees were analyzed, ninety unrelated families encompassing 1,007 individuals were identified; among relatives, other 35 manifested HD, and 106 died of HD. Besides, five hundred seventy-nine individuals were at genetic risk. The minimum estimated prevalence of HD in Chile in 2019 was 0.72 × 100,000 inhabitants. The mean CAG repeats (CAGR) of 47.2 ± 10.74 for the expanded allele and 17.93 ± 2.05 for the normal allele. The mean age of onset was 41.39 ± 13.47 years. Juvenile cases represented 7.8% of this cohort, and 4.9% had a late onset. There was a negative correlation between the age of onset and the CAGR of the expanded allele (r =-0.84 p < 0.0001). Besides, 79.6% had a family history of HD. CONCLUSIONS: This is the first report characterizing genetics, motor, and neuropsychiatric features in patients with HD in Chile. The mean length of CAGR expansion of the abnormal allele was similar to previous reports in North America (i.e., Mexico and Canada) and higher than that reported in the neighboring country of Argentina. According to previous estimations, the minimal prevalence of HD in Chile may be lower than expected.

Wnt/ß-Catenin Signaling in Craniomaxillofacial Osteocytes.

PURPOSE OF REVIEW: There is a growing appreciation within the scientific community that cells exhibit regional variation. Whether the variation is attributable to differences in embryonic origin or anatomical location and mechanical loading has not been elucidated; what is clear, however, is that adult cells carry positional information that ultimately affects their functions. The purpose of this review is to highlight the functions of osteocytes in the craniomaxillofacial (CMF) skeleton as opposed to elsewhere in the body, and in doing so gain mechanistic insights into genetic conditions and chemically-induced diseases that particularly affect this region of our anatomy. RECENT FINDINGS: In the CMF skeleton, elevated Wnt/ß-catenin signaling affects not only bone mass and volume, but also mineralization of the canalicular network and osteocyte lacunae. Aberrant elevation in the Wnt/ß-catenin pathway can also produce micropetrosis and osteonecrosis of CMF bone, presumably due to a disruption in the signaling network that connects osteocytes to one another, and to osteoblasts on the bone surface.

Characterizing the Genetic Architecture of Parkinson's Disease in Latinos.

OBJECTIVE: This work was undertaken in order to identify Parkinson's disease (PD) risk variants in a Latino cohort, to describe the overlap in the genetic architecture of PD in Latinos compared to European-ancestry subjects, and to increase the diversity in PD genome-wide association (GWAS) data. METHODS: We genotyped and imputed 1,497 PD cases and controls recruited from nine clinical sites across South America. We performed a GWAS using logistic mixed models; variants with a p-value <1 × 10-5 were tested in a replication cohort of 1,234 self-reported Latino PD cases and 439,522 Latino controls from 23andMe, Inc. We also performed an admixture mapping analysis where local ancestry blocks were tested for association with PD status. RESULTS: One locus, SNCA, achieved genome-wide significance (p-value <5 × 10-8 ); rs356182 achieved genome-wide significance in both the discovery and the replication cohorts (discovery, G allele: 1.58 OR, 95% CI 1.35-1.86, p-value 2.48 × 10-8 ; 23andMe, G allele: 1.26 OR, 95% CI 1.16-1.37, p-value 4.55 × 10-8 ). In our admixture mapping analysis, a locus on chromosome 14, containing the gene STXBP6, achieved significance in a joint test of ancestries and in the Native American single-ancestry test (p-value <5 × 10-5 ). A second locus on chromosome 6, containing the gene RPS6KA2, achieved significance in the African single-ancestry test (p-value <5 × 10-5 ). INTERPRETATION: This study demonstrated the importance of the SNCA locus for the etiology of PD in Latinos. By leveraging the demographic history of our cohort via admixture mapping, we identified two potential PD risk loci that merit further study. ANN NEUROL 2021;90:353-365.

Genome-Wide Analysis of Copy Number Variation in Latin American Parkinson's Disease Patients.

BACKGROUND: Parkinson's disease is the second most common neurodegenerative disorder and affects people from all ethnic backgrounds, yet little is known about the genetics of Parkinson's disease in non-European populations. In addition, the overall identification of copy number variants at a genome-wide level has been understudied in Parkinson's patients. The objective of this study was to understand the genome-wide burden of copy number variants in Latinos and its association with Parkinson's disease. METHODS: We used genome-wide genotyping data from 747 Parkinson's disease patients and 632 controls from the Latin American Research Consortium on the Genetics of Parkinson's disease. RESULTS: Genome-wide copy number burden analysis showed that patients were significantly enriched for copy number variants overlapping known Parkinson's disease genes compared with controls (odds ratio, 3.97; 95%CI, 1.69-10.5; P = 0.018). PRKN showed the strongest copy number burden, with 20 copy number variant carriers. These patients presented an earlier age of disease onset compared with patients with other copy number variants (median age at onset, 31 vs 57 years, respectively; P = 7.46 × 10-7 ). CONCLUSIONS: We found that although overall genome-wide copy number variant burden was not significantly different, Parkinson's disease patients were significantly enriched with copy number variants affecting known Parkinson's disease genes. We also identified that of 250 patients with early-onset disease, 5.6% carried a copy number variant on PRKN in our cohort. Our study is the first to analyze genome-wide copy number variant association in Latino Parkinson's disease patients and provides insights about this complex disease in this understudied population. © 2020 International Parkinson and Movement Disorder Society.

Epidemiology of Parkinson's Disease in Chile.

INTRODUCTION: Parkinson's disease (PD) is one of the most common neurodegenerative disorders. There is no epidemiological description of PD in Chile and not many descriptions in Latin America. This study aims to describe the incidence and prevalence of PD in Chile. METHODS: The study group was the population on the public health system in Chile between 2010 and 2018 that were registered in the GES system as having PD. Crude and standardized prevalence and incidence were calculated with a 95% confidence interval. RESULTS: 33,345 patients were found in the register as confirmed cases with PD. The crude incidence in 2018 was 23.7/100,000; the crude prevalence in 2018 was 160.7/100,000. The male-to-female ratio was 1.03. CONCLUSION: The prevalence and incidence observed in the Chilean population are consistent with studies from other countries.

Localization System for Lightweight Unmanned Aerial Vehicles in Inspection Tasks.

This paper presents a localization system for Unmanned Aerial Vehicles (UAVs) especially designed to be used in infrastructure inspection, where the UAVs have to fly in challenging conditions, such as relatively high altitude (e.g., 15 m), eventually with poor or absent GNSS (Global Navigation Satellite System) signal reception, or the need for a BVLOS (Beyond Visual Line of Sight) operation in some periods. In addition, these infrastructure inspection applications impose the following requirements for the localization system: defect traceability, accuracy, reliability, and fault tolerance. Our system proposes a lightweight solution combining multiple stereo cameras with a robotic total station to comply with these requirements, providing full-state estimation (i.e., position, orientation, and linear and angular velocities) in a fixed and time-persistent reference frame. Moreover, the system can align and fuse all sensor measurements in real-time at high frequency. We have integrated this localization system in our aerial platform, and we have tested its performance for inspection in a real-world viaduct scenario, where the UAV has to operate with poor or absent GNSS signal at high altitude.

[Hospital admissions in Chile among patients with Parkinson's disease from 2001 to 2018]. / Hospitalización de pacientes con enfermedad de Parkinson en la población chilena entre 2001 y 2018.

BACKGROUND: The progression of Parkinson's disease is associated with complications, most of them preventable. AIM: To analyze hospitalizations with a diagnosis of Parkinson's disease in Chile, comparing the different health subsystems. MATERIAL AND METHODS: Analysis of hospital discharge database available at the website of the Chilean Ministry of Health. Discharges that incorporated the diagnosis of Parkinson's disease (ICD 10 code G20), between the years 2001 and 2018 were analyzed. RESULTS: The rate of discharges with the diagnosis of Parkinson's disease was 34.5 per 100,000 hospitalizations. The figures were 55.2 and 29.8 discharges per 100,000 in 2001 and 2018, respectively. Sixty seven percent of hospital admissions for Parkinson's occurred in the public sector and corresponded to beneficiaries of the public health insurance system (FONASA). Beneficiaries of private insurance systems accounted for 12% of hospital admissions. The mean hospital stay was 13.4 days. CONCLUSIONS: There is a decrease over time in the rate of hospitalizations with Parkinson's disease. This trend may be related with the incorporation of this disease in a special governmental program that guarantees a timely access to diagnosis and treatment.

Insulin-like growth factor 2 (IGF2) protects against Huntington's disease through the extracellular disposal of protein aggregates.

Impaired neuronal proteostasis is a salient feature of many neurodegenerative diseases, highlighting alterations in the function of the endoplasmic reticulum (ER). We previously reported that targeting the transcription factor XBP1, a key mediator of the ER stress response, delays disease progression and reduces protein aggregation in various models of neurodegeneration. To identify disease modifier genes that may explain the neuroprotective effects of XBP1 deficiency, we performed gene expression profiling of brain cortex and striatum of these animals and uncovered insulin-like growth factor 2 (Igf2) as the major upregulated gene. Here, we studied the impact of IGF2 signaling on protein aggregation in models of Huntington's disease (HD) as proof of concept. Cell culture studies revealed that IGF2 treatment decreases the load of intracellular aggregates of mutant huntingtin and a polyglutamine peptide. These results were validated using induced pluripotent stem cells (iPSC)-derived medium spiny neurons from HD patients and spinocerebellar ataxia cases. The reduction in the levels of mutant huntingtin was associated with a decrease in the half-life of the intracellular protein. The decrease in the levels of abnormal protein aggregation triggered by IGF2 was independent of the activity of autophagy and the proteasome pathways, the two main routes for mutant huntingtin clearance. Conversely, IGF2 signaling enhanced the secretion of soluble mutant huntingtin species through exosomes and microvesicles involving changes in actin dynamics. Administration of IGF2 into the brain of HD mice using gene therapy led to a significant decrease in the levels of mutant huntingtin in three different animal models. Moreover, analysis of human postmortem brain tissue and blood samples from HD patients showed a reduction in IGF2 level. This study identifies IGF2 as a relevant factor deregulated in HD, operating as a disease modifier that buffers the accumulation of abnormal protein species.

Pharmacokinetic evaluation of [18F]PR04.MZ for PET/CT imaging and quantification of dopamine transporters in the human brain.

PURPOSE: Dopamine transporters (DAT) modulate pre-synaptic dopamine and physiological functions such as movement and reward. DAT also mirrors disease state in neurological disorders, rendering it an essential diagnostic target. [18F]PR04.MZ is a new PET imaging agent for DAT with an improved affinity and selectivity profile, for which we here describe the complete pharmacokinetic evaluation in healthy controls. METHODS: Thirty-two healthy subjects underwent T1-weighted MRI and dynamic PET scans for 180 min with arterial blood sampling (n = 5) or 90 min without blood sampling (n = 25) after injection of 197.6 ± 12.2 MBq [18F]PR04.MZ. Blood and plasma metabolite analysis were performed. MRI-based normalization of brain images, delineation of VOIs, and kinetic modeling was conducted to determine distribution volumes (Vt) and binding potentials (BPnd). The impact of scan duration was evaluated and repeated PET scans were performed to assess test-retest variability (n = 5). A static imaging protocol has been validated for clinical applications. RESULTS: [18F]PR04.MZ showed rapid metabolization in circulation, very high uptake in striatum and midbrain, and very low non-specific binding. The two-tissue compartment model 2TCM provided best fits for measured time-activity-curves and calculated Vts in putamen, caudate, substantia nigra pars compacta (SNpc), and cerebellar cortex were 11.83, 9.73, 2.12, and 0.57, respectively. All non-invasive models correlated well with BPnd values derived from 2TCM but underestimated DAT availability by about 28-33%. Of those, simplified reference tissue model (SRTM) provided the best fits, lowest Akaike Information Criteria values, and BPnd values of 14.82, 11.95, and 2.63 in putamen, caudate, and SNpc, respectively. BPnd estimates for striatal regions and SNpc were stable between 90 and 130 min post-injection. Test-retest results were excellent, showing low variability in all and excellent reliability in most relevant regions. Static imaging from 60 to 90-min post-injection is a viable alternative for quantification. CONCLUSIONS: [18F]PR04.MZ is a PET tracer with very high affinity, selectivity, and specific uptake in striatum and midbrain. 2TCM and SRTM provide good fits, high and stable Vts or BPnds, and good test-retest reliability for precise quantification of DAT in human subjects.

Fully-Actuated Aerial Manipulator for Infrastructure Contact Inspection: Design, Modeling, Localization, and Control.

This paper presents the design, modeling and control of a fully actuated aerial robot for infrastructure contact inspection as well as its localization system. Health assessment of transport infrastructure involves measurements with sensors in contact with the bridge and tunnel surfaces and the installation of monitoring sensing devices at specific points. The design of the aerial robot presented in the paper includes a 3DoF lightweight arm with a sensorized passive joint which can measure the contact force to regulate the force applied with the sensor on the structure. The aerial platform has been designed with tilted propellers to be fully actuated, achieving independent attitude and position control. It also mounts a "docking gear" to establish full contact with the infrastructure during the inspection, minimizing the measurement errors derived from the motion of the aerial platform and allowing full contact with the surface regardless of its condition (smooth, rough, ...). The localization system of the aerial robot uses multi-sensor fusion of the measurements of a topographic laser sensor on the ground and a tracking camera and inertial sensors on-board the aerial robot, to be able to fly under the bridge deck or close to the bridge pillars where GNSS satellite signals are not available. The paper also presents the modeling and control of the aerial robot. Validation experiments of the localization system and the control system, and with the aerial robot inspecting a real bridge are also included.

[Nonmotor symptoms in 32 patients with Parkinson disease]. / Evaluación de síntomas no motores y descontrol de impulsos en usuarios con enfermedad de Parkinson por el médico en atención primaria.

BACKGROUND: Nonmotor symptoms of Parkinson disease significantly hamper the quality of life of patients and have prognostic significance. AIM: To evaluate the presence of nonmotor symptoms in patients with Parkinson disease. MATERIAL AND METHODS: A structured interview was carried out in 32 patients aged 74 ± 9 years (53% men) with Parkinson disease asking specifically for impulse control disorders and dopaminergic dysregulation. The following scales were also applied: Hoehn & Yahr scale, Montreal Cognitive Assessment, Geriatric depression scale, Nonmotor symptom scale and REM sleep scale. RESULTS: A high frequency of nonmotor symptoms was recorded, specially mood, sleep, urinary and gastrointestinal problems and impulse control disorders. CONCLUSIONS: Nonmotor symptoms must be actively sought and managed in patients with Parkinson disease.

Robotic System for Inspection by Contact of Bridge Beams Using UAVs.

This paper presents a robotic system using Unmanned Aerial Vehicles (UAVs) for bridge-inspection tasks that require physical contact between the aerial platform and the bridge surfaces, such as beam-deflection analysis or measuring crack depth with an ultrasonic sensor. The proposed system takes advantage of the aerodynamic ceiling effect that arises when the multirotor gets close to the bridge surface. Moreover, this paper describes how a UAV can be used as a sensor that is able to fly and touch the bridge to take measurements during an inspection by contact. A practical application of the system involving the measurement of a bridge's beam deflection using a laser tracking station is also presented. In order to validate our system, experiments on two different bridges involving the measurement of the deflection of their beams are shown.

Reduced Anterolateral Thigh Flap Donor-Site Morbidity Using Incisional Negative Pressure Therapy.

BACKGROUND: Primary closure of the donor-site after harvest of a large anterolateral thigh flap (ALT) is associated with significant morbidity. Incisional negative pressure therapy (INPT) may decrease complications in high-risk incisions. This study assessed if the incidence of complications after primary closure of the ALT flap donor-site decreases with INPT. METHODS: Retrospective cohort study of a prospectively maintained database including patients who underwent upper and lower limb reconstruction, using an ALT free flap with primary closure of the donor-site. Two groups were defined: primary closure and INPT (study group) and primary closure with traditional dressings (control group). Nonparametric statistics were employed to identify prognostic factors, p < 0,05. RESULTS: Fifty-eight free ALT flaps in 58 patients (study group n = 28; control group n = 30) were included. Median flap width and length were 9 cm (range: 5-14) and 25 cm (range: 10-48), respectively. Median follow-up was 19 months (range: 3-78 months). No significant differences in age or flap size were identified in both groups (p > 0.05). The global complication rate was 7.14% (n = 2) in the INPT group, and 37% (n = 11) in the control group (p = 0.007). The study group had a lower dehiscence and skin necrosis rate (p < 0.05). Multivariate logistic regression analysis showed IPNT was associated with a significant reduction of donor-site complications (p = 0.006), especially in patients with defects > 8 cm (p = 0.003). CONCLUSION: In this cohort study the use of INPT significantly reduced the donor-site morbidity after ALT flap harvest.

Evaluation of cardiovascular responses to silver nanoparticles (AgNPs) in spontaneously hypertensive rats.

Silver nanoparticles (AgNPs) are used in the medical, pharmaceutical and food industry. Adverse effects and toxicity induced by AgNPs upon cardiac function related to nitric oxide (NO) and oxidative stress (OS) are described. AgNPs-toxicity may be influenced by cardiovascular pathologies such as hypertension. However, the molecules involved under pathophysiological conditions are not well studied. The aim of this work was to evaluate perfusion pressure (PP) and left ventricle pressure (LVP) as physiological parameters of cardiovascular function in response to AgNPs, using isolated perfused hearts from spontaneously hypertensive rats (SHR), and identify the role of NO and OS. The results suggest that AgNPs reduced NO derived from endothelial/inducible NO-synthase and increased OS, leading to increased and sustained vasoconstriction and myocardial contractility. Additionally, the hypertension condition alters phenylephrine (Phe) and acetylcholine (ACh) classic effects. These data suggest that hypertension intensified AgNPs-cardiotoxicity. Nevertheless, the precise mechanism of action is still under elucidation.

[Clinical features of 63 patients with ataxia]. / Características clínicas de 63 pacientes con ataxia.

BACKGROUND: Ataxia can be classified as genetic, sporadic or acquired. AIM: To report the clinical features of a group of patients with ataxia. MATERIAL AND METHODS: Review of medical records of patients consulting in a specialized center in movement disorders. Those records in which the diagnosis of "ataxia" or "ataxic syndrome" appeared, were selected for the review. RESULTS: Of 4,282 records surveyed, the diagnosis of ataxia appeared in 95. After eliminating repeated or incomplete records, 63 were reviewed. RESULTS: Ataxia was sporadic, genetic and acquired in 27, 22 and 14 patients, respectively. The mean age at presentation for genetic, acquired and sporadic ataxia was 24, 46 and 53 years respectively. All autosomal dominant ataxias were type 3 spinocerebellar ataxia (SCA). Friedrich's ataxia was the most common recessive form. Most sporadic forms of ataxia were multiple system atrophy with predominant cerebellar ataxia (MSA-C) subtype. CONCLUSIONS: Considering the heterogeneity of patients with ataxia, we propose a method to approach them.