Unveiling the role of subjective cognitive complaints in predicting cognitive impairment in Parkinson´s Disease- A longitudinal study with 4 year of follow up.

BACKGROUND: Emerging data associated subjective cognitive complaints (SCC) with a heightened risk of future cognitive decline in Parkinson´s Disease (PD). OBJECTIVE: To determine whether SCC may predict the development of cognitive impairment in PD patients at baseline. METHODS: Over 4 years, major aspects of motor and non-motor symptoms were assessed. SCC were evaluated by non-motor symptoms scale domain-5 (NMSS5). The predictor value of SCC in cognitive change was assessed with univariate linear regression analyses, with NMSS5 at baseline as predictor. Change in cognition (ΔMoCA) was calculated by subtracting Montreal Cognitive Assessment Scale (MoCA) scores at baseline from scores obtained at reassessment and employed as the outcome. We replicated these analyses by employing alterations in MoCA subdomains as outcomes. RESULTS: 134 patients were evaluated at baseline, of those 73 PD patients were reassessed four years later. In our study, SCC didn´t act as a predictor for future cognitive decline. However, baseline NMSS5 was associated significantly with variation in attention, naming, and orientation domains. CONCLUSION: Our findings did not support that SCC in PD patients acts as a predictor of global cognitive decline. However, our findings enhance comprehension of how SCC correlates with performance in distinct cognitive areas, thereby providing better guidance for patients on their current complaints.

Comparison of Synthetic Pathways for Obtaining Fluorescent Nanomaterials Based on Halloysite and Carbon Dots for Potential Biological Sensing.

Recently, fluorescent sensors have gained considerable attention due to their high sensitivity, low cost and noninvasiveness. Among the different materials that can be used for this purpose, carbon dots (CDs) represent valuable candidates for applications in sensing. These, indeed, are easily synthesized, show high quantum yield and are highly biocompatible. However, it was pointed out that the photoluminescence properties of these nanomaterials are strictly dependent on the synthetic and purification methods adopted. The presence of halloysite nanotubes (HNTs), a natural, low cost and biocompatible clay mineral, has been found to be efficient in obtaining small and highly monodispersed CDs without long and tedious purification techniques. Herein, we report the comparison of synthetic pathways for obtaining halloysite-N-doped CDs (HNTs-NCDs) that could be used in biological sensing. One was based on the synthesis of N-doped CDs by a bottom-up approach on HNTs' surface by a MW pyrolysis process; the other one was based on the post-modification of pristine N-doped CDs with halloysite derivatives. The evaluation of the best synthetic route was performed by different physico-chemical techniques. It was found that the bottom-up approach led to the formation of N-doped CDs with different functional groups onto the HNTs' surface. This evidence was also translated in the different fluorescence quantum yields and the existence of several functional groups in the obtained materials was investigated by potentiometric titrations. Furthermore, the ability of the synthesized nanomaterials as sensors for Fe3+ ions detection was assessed by spectroscopic measurements, and the cellular uptake was verified by confocal/fluorescence microscopies as well.

New proposal of viral genome representation applied in the classification of SARS-CoV-2 with deep learning.

BACKGROUND: In December 2019, the first case of COVID-19 was described in Wuhan, China, and by July 2022, there were already 540 million confirmed cases. Due to the rapid spread of the virus, the scientific community has made efforts to develop techniques for the viral classification of SARS-CoV-2. RESULTS: In this context, we developed a new proposal for gene sequence representation with Genomic Signal Processing techniques for the work presented in this paper. First, we applied the mapping approach to samples of six viral species of the Coronaviridae family, which belongs SARS-CoV-2 Virus. We then used the sequence downsized obtained by the method proposed in a deep learning architecture for viral classification, achieving an accuracy of 98.35%, 99.08%, and 99.69% for the 64, 128, and 256 sizes of the viral signatures, respectively, and obtaining 99.95% precision for the vectors with size 256. CONCLUSIONS: The classification results obtained, in comparison to the results produced using other state-of-the-art representation techniques, demonstrate that the proposed mapping can provide a satisfactory performance result with low computational memory and processing time costs.

Global RNAseq of ocular cells reveals gene dysregulation in both asymptomatic and with Congenital Zika Syndrome infants exposed prenatally to Zika virus.

In 2015, Brazil reported an outbreak identified as Zika virus (ZIKV) infection associated with congenital abnormalities. To date, a total of 86 countries and territories have described evidence of Zika infection and recently the appearance of the African ZIKV lineage in Brazil highlights the risk of a new epidemic. The spectrum of ZIKV infection-induced alterations at both cellular and molecular levels is not completely elucidated. Here, we present for the first time the gene expression responses associated with prenatal ZIKV infection from ocular cells. We applied a recently developed non-invasive method (impression cytology) which use eye cells as a model for ZIKV studies. The ocular profiling revealed significant differences between exposed and control groups, as well as a different pattern in ocular transcripts from Congenital Zika Syndrome (CZS) compared to ZIKV-exposed but asymptomatic infants. Our data showed pathways related to mismatch repair, cancer, and PI3K/AKT/mTOR signaling and genes probably causative or protective in the modulation of ZIKV infection. Ocular cells revealed the effects of ZIKV infection on primordial neuronal cell genes, evidenced by changes in genes associated with embryonic cells. The changes in gene expression support an association with the gestational period of the infection and provide evidence for the resulting clinical and ophthalmological pathologies. Additionally, the findings of cell death- and cancer-associated deregulated genes raise concerns about the early onset of other potential pathologies including the need for tumor surveillance. Our results thus provide direct evidence that infants exposed prenatally to the Zika virus, not only with CZS but also without clinical signs (asymptomatic) express cellular and molecular changes with potential clinical implications.

Distinct gait dimensions are modulated by physical activity in Parkinson's disease patients.

Parkinson's disease (PD) is the fastest growing neurodegenerative disease, but disease-modifying or preventive treatments are lacking. Physical activity is a modifiable factor that decreases the PD risk and improves motor symptoms in PD. Understanding which dimensions of gait performance correlate with physical activity in PD can have important pathophysiological and therapeutic implications. Clinical/demographic data together with physical activity levels were collected from thirty-nine PD patients. Gait analysis was performed wearing seven inertial measurement units on the lower body, reconstructing the subjects' lower body motion using 3D kinematic biomechanical models. Higher physical activity scores were significantly correlated with MDS-UPDRS part III scores (r = - 0.58, p value = 9.2 × 10-5), age (r = - 0.39, p value = 1.5 × 10-2) and quality-of-life (r = - 0.47, p value = 5.9 × 10-3). Physical activity was negatively associated with MDS-UPDRS part III scores after adjusting for age and disease duration (ß = - 0.08530, p value = 0.0010). The effect of physical activity on quality-of-life was mediated by the MDS-UPDRS part III (62.10%, 95% CI = 0.0758-1.78, p value = 0.022). The level of physical activity was correlated primarily with spatiotemporal performance. While spatiotemporal performance displays the strongest association with physical activity, other quality-of-movement dimensions of clinical relevance (e.g., smoothness, rhythmicity) fail to do so. Interventions targeting these ought to be leveraged for performance enhancement in PD through neuroprotective and brain network connectivity strengthening. It remains to be ascertained to which extent these are amenable to modulation.

Convolutional Neural Network Applied to SARS-CoV-2 Sequence Classification.

COVID-19, the illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus belonging to the Coronaviridade family, a single-strand positive-sense RNA genome, has been spreading around the world and has been declared a pandemic by the World Health Organization. On 17 January 2022, there were more than 329 million cases, with more than 5.5 million deaths. Although COVID-19 has a low mortality rate, its high capacities for contamination, spread, and mutation worry the authorities, especially after the emergence of the Omicron variant, which has a high transmission capacity and can more easily contaminate even vaccinated people. Such outbreaks require elucidation of the taxonomic classification and origin of the virus (SARS-CoV-2) from the genomic sequence for strategic planning, containment, and treatment of the disease. Thus, this work proposes a high-accuracy technique to classify viruses and other organisms from a genome sequence using a deep learning convolutional neural network (CNN). Unlike the other literature, the proposed approach does not limit the length of the genome sequence. The results show that the novel proposal accurately distinguishes SARS-CoV-2 from the sequences of other viruses. The results were obtained from 1557 instances of SARS-CoV-2 from the National Center for Biotechnology Information (NCBI) and 14,684 different viruses from the Virus-Host DB. As a CNN has several changeable parameters, the tests were performed with forty-eight different architectures; the best of these had an accuracy of 91.94 ± 2.62% in classifying viruses into their realms correctly, in addition to 100% accuracy in classifying SARS-CoV-2 into its respective realm, Riboviria. For the subsequent classifications (family, genera, and subgenus), this accuracy increased, which shows that the proposed architecture may be viable in the classification of the virus that causes COVID-19.

Enrichment of Hydrogen Oxidizing Bacteria from High Temperature and Salinity Environments.

There is an urgent need for sustainable protein supply routes with low environmental footprint. Recently, the use of hydrogen oxidizing bacteria (HOB) as a platform for high quality microbial protein (MP) production has regained interest. This study aims to investigate the added value of using conditions such as salt and temperature to steer HOB communities to lower diversities, while maintaining a high protein content and a high quality amino acid profile. Pressure drop and hydrogen consumption were measured for 56 days to evaluate autotrophy of a total of six communities in serum flasks. Of the six communities, four were enriched under saline (0.0, 0.25, 0.5 and 1.0 mol NaCl l-1) and two under thermophilic conditions (65°C). Five communities enriched for HOB were subsequently cultivated in continuously stirred reactors under the same conditions to evaluate their potential as microbial protein producers. The protein percentages ranged from 41 to 80%. The highest protein content was obtained for the thermophilic enrichments. Amino acid profiles were comparable to protein sources commonly used for feed purposes. Members of the genus Achromobacter were found to dominate the saline enrichments while members of the genus Hydrogenibacillus were found to dominate the thermophilic enrichments. Here we show that enriching for HOB while steering the community toward low diversity and maintaining a high quality protein content can be successfully achieved, both in saline and thermophilic conditions.IMPORTANCE Alternative feed and food supply chains are required to decrease water and land use. HOB offer a promising substitute for traditional agricultural practice to produce microbial protein (MP) from residual materials and renewable energy. To safeguard product stability, the composition of the HOB community should be controlled. Defining strategies to maintain the stability of the communities is therefore key for optimization purposes. In this study, we use salt and temperature as independent conditions to stabilize the composition of the HOB communities. Based on the results presented, we conclude that HOB communities can be steered to have low diversity using the presented conditions while producing a desirable protein content with a valuable amino acid profile.

REM sleep behaviour disorder in essential tremor: A polysomnographic study.

Our objectives were to assess the prevalence of REM sleep behaviour disorder in patients with Essential Tremor, using video-polysomnography and to compare REM sleep behaviour disorder features in essential tremor with those of patients with alpha-synucleinopathies. Forty-nine patients with essential tremor were screened with the REM Sleep Behaviour Disorder Screening Questionnaire. Patients scoring positive and those with spontaneous complaints of REM sleep behaviour disorder (n = 6) underwent video-polysomnography. The clinical features of essential tremor were compared between patients with and without REM sleep behaviour disorder. Video-polysomnography data were compared between patients who had essential tremor and Parkinson's disease with REM sleep behaviour disorder and those with idiopathic REM sleep behaviour disorder. Fourteen patients (23.5%) screened positive for REM sleep behaviour disorder, confirmed by video-polysomnography in five (11.6%). All patients with essential tremor and REM sleep behaviour disorder had rest tremor, compared with 13 (34.2%) in the group with essential tremor but without REM sleep behaviour disorder (p = .009). In video-polysomnography, patients with essential tremor and REM sleep behaviour disorder were similar to patients with Parkinson's disease with REM sleep behaviour disorder and presented worse sleep dysfunction and lower severity of REM sleep behaviour disorder compared to those with idiopathic REM sleep behaviour disorder. We found a high prevalence of REM sleep behaviour disorder in patients with essential tremor, associated with a predominance of rest tremor. Polysomnography data from patients with essential tremor and REM sleep behaviour disorder were similar to those in patients with Parkinson's disease. This suggests a relation between this subgroup of patients with essential tremor and the alpha-synucleinopathies.

Do dreams tell the future? Dream content as a predictor of cognitive deterioration in Parkinson's disease.

Cross-sectional studies suggest a correlation between alterations in dream content reports and executive dysfunction tests in Parkinson's disease (PD), but this has not been assessed in longitudinal studies. Our objective was to assess the predictive value of dream content for progression of cognitive dysfunction in PD. We prospectively addressed all consecutive, non-demented patients with PD attending an outpatient clinic during a 1-year period. Dream reports were collected at baseline by means of a dream diary and analysed according to the Hall and Van de Castle system. Patients were assessed at baseline for rapid eye movement sleep behaviour disorder, motor stage, mood disorder and psychosis. The Montreal Cognitive Assessment (MoCA) was applied at baseline and 4 years later. Linear regression analysis was used to the test the relation between each dream index (predictors), demographic and other motor and non-motor variables (covariates), and change in MoCA scores (dependent variable). In all, 58 patients were assessed at both time points and 23 reported at least one dream (range 1-27, total 148). Aggression, physical activities, and negatively toned content predominated in dream reports. The MoCA scores decreased significantly from baseline to follow-up. In the multivariate model, negative emotion index was the strongest predictor of cognitive decline. We found a significant positive association between negative emotions in dreams at baseline and subsequent reduction in MoCA scores. These findings suggest that some dream content in patients with PD could be considered a predictor of cognitive decline, independent of other factors known to influence either dream content or cognitive deterioration.

Cellular Imprinting Proteomics Assay: A Novel Method for Detection of Neural and Ocular Disorders Applied to Congenital Zika Virus Syndrome.

Congenital Zika syndrome was first described due to increased incidence of congenital abnormalities associated with Zika virus (ZIKV) infection. Since the eye develops as part of the embryo central nervous system (CNS) structure, it becomes a specialized compartment able to display symptoms of neurodegenerative diseases and has been proposed as a noninvasive approach to the early diagnosis of neurological diseases. Ocular lesions result from defects that occurred during embryogenesis and can become apparent in newborns exposed to ZIKV. Furthermore, the absence of microcephaly cannot exclude the occurrence of ocular lesions and other CNS manifestations. Considering the need for surveillance of newborns and infants with possible congenital exposure, we developed a method termed cellular imprinting proteomic assay (CImPA) to evaluate the ocular surface proteome specific to infants exposed to ZIKV during gestation compared to nonexposure. CImPA combines surface cells and fluid capture using membrane disks and a large-scale quantitative proteomics approach, which allowed the first-time report of molecular alterations such as neutrophil degranulation, cell death signaling, ocular and neurological pathways, which are associated with ZIKV infection with and without the development of congenital Zika syndrome, CZS. Particularly, infants exposed to ZIKV during gestation and without early clinical symptoms could be detected using the CImPA method. Lastly, this methodology has broad applicability as it could be translated in the study of several neurological diseases to identify novel diagnostic biomarkers. Data are available via ProteomeXchange with identifier PXD014038.

Early Repolarization Pattern and Left Ventricular Mass in Hypertrophic Cardiomyopathy.

BACKGROUND: J-point elevation in the inferior and/or lateral leads is associated with an increased incidence of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM), although the exact underlying mechanism is not known. As severe left ventricular hypertrophy and late gadolinium enhancement (LGE) are important risk factors for SCD in this population, we aimed to assess whether there was an association between an early repolarization pattern (ERP) and greater left ventricular mass (LVM) and LGE extent among patients with HCM. METHODS: This was a retrospective cohort study of 85 consecutive patients with HCM who underwent cardiac magnetic resonance (CMR) and had an electrocardiogram without confounders (intraventricular conduction delay, complete left or right bundle branch block, or ventricular paced rhythm). Baseline characteristics and MRI-derived LVM and LGE extent were compared between patients with and without ERP. RESULTS: ERP was present in 9 out of 85 patients (10.6%). Patients with ERP had greater indexed LVM compared to those without (112.5 ± 26.3 vs. 87.8 ± 24.6 g/m2, p = 0.006). Logistic regression analysis revealed a 4.2-fold increase in the odds of prevalent ERP per standard deviation increase in body surface area-indexed LVM (odds ratio 4.2; 95% CI 1.54-11.4, p = 0.005). There were no statistically significant differences regarding LGE extent between groups. CONCLUSION: ERP is associated with greater CMR-derived LVM among patients with HCM. This finding could partially explain the association between J waves and a higher risk of SCD in this population. There were no differences in LGE extent. Further studies are needed to confirm this association and evaluate the importance of ERP as a marker of increased risk of SCD in HCM.

Proposal of the CAD System for Melanoma Detection Using Reconfigurable Computing.

This work proposes dedicated hardware to real-time cancer detection using Field-Programmable Gate Arrays (FPGA). The presented hardware combines a Multilayer Perceptron (MLP) Artificial Neural Networks (ANN) with Digital Image Processing (DIP) techniques. The DIP techniques are used to extract the features from the analyzed skin, and the MLP classifies the lesion into melanoma or non-melanoma. The classification results are validated with an open-access database. Finally, analysis regarding execution time, hardware resources usage, and power consumption are performed. The results obtained through this analysis are then compared to an equivalent software implementation embedded in an ARM A9 microprocessor.

Preparation, characterisation and cell viability of encapsulated Trichoderma asperellum in alginate beads.

Aim: The encapsulation of Trichoderma asperellum BRM-29104 using Ca-alginate matrix was evaluated.Methods: Intact and freeze-dried beads containing submerged conidia and microsclerotia (MS) of T. asperellum grown in liquid culture were prepared and characterised. Beads were stored at 8, 25, and 35 °C over 120 days.Results: The mean sizes of beads before and after freeze-drying were 2.5 ± 0.2 mm and 1.5 × 1.1 mm (± 0.1 mm), respectively. Freeze-dried beads stored at 8 °C were more effective in maintaining conidia concentration, while MS concentrations yielded 102 MS/g for both beads at 8 and 25 °C. The concentration of viable cells in freeze-dried beads stored at 8 °C attained 3.0 × 108 CFU/g after 120 days. FIRT analysis showed an interaction between the alginate and the cell wall of the fungus.Conclusion: These findings support the use of alginate beads followed by freeze drying and cold storage for maintenance of viability of T. asperellum.

Cognitive complaints in Parkinson's disease patients: from subjective cognitive complaints to dementia and affective disorders.

Subjective cognitive complaints (SCC) are frequent in elderly populations. PD patients report SCC more often than healthy controls. The association between SCC, objective cognitive impairment and affective symptoms remains controversial. We assessed consecutive PD patients between March 2014 and March 2015. Presence of SCC was defined as a score ≥ 1 in the Non-Motor Symptom Assessment Scale for Parkinson's Disease (NMSS) Domain 5. MoCA was used for cognitive impairment assessment. Pill Questionnaire measured the impact in daily activities. PD with Dementia (PDD) and PD with Mild Cognitive Impairment (PDMCI) were defined as the presence of cognitive impairment with or without impact on daily activities. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scales. Significance was set at p < 0.05. From 134 patients, 128 were included. PDD was diagnosed in 21 (16.4%), PDMCI in 31 (24.2%), and 76 (59.4%) had normal cognition (PDCN). SCC were present in 85% of whole cohort and evenly distributed (p = 0.361), PDD (95.2%), PDMCI (83.9%) and PDCN (82.9%). Severity was significantly different between PDD (20.00 ± 10.81), PDMCI (6.54 ± 5.5) and PDCN (6.97 ± 6.98), p < 0.001. A score ≥ 19 had a specificity of 77.3% and a sensitivity of 78.8% for identifying PDD. In PDCN, SCC severity was found to be related to depression (OR 1.23, CI 95% 1.02-1.47, p = 0.026) more than with MoCA scores (OR: 0.86, CI 95% 0.69-1.05, p = 0.141). SCC are common in PD. Their severity can help distinguish PDD from non-demented PD patients. In PDCN, SCC should alert the clinician for an affective disorder.

Motor and non-motor function predictors of mortality in Parkinson's disease.

Doubts persist regarding the influence of Parkinson's disease (PD) on mortality. Our objective was to assess mortality rates in a prospectively followed cohort of PD patients and the impact of motor and non-motor symptoms in survival. 130 consecutive PD patients were followed during a 4-year period or until death. Baseline assessment included motor function (UPDRSIII, Hoehn and Yahr-HY), incapacity (Schwab and England-S&E, UPDRS II), Health-Related quality of life (EuroQol), non-motor symptoms (Non-Motor Symptom Scale-NMSS, MoCA, REM sleep behavior disorder symptoms questionnaire) and comorbidity burden (Charlson Comorbidity Index-CCI). These were used as predictor variables. Standardized mortality rates (SMR) were calculated, comparing with the general population. The association between mortality and predictors was tested with univariate and multivariate Cox proportional hazard regression models. Overall and gender-related SMRs were similar to the general population. SMR for pneumonia was five times higher than in the general population. Age, disease duration, CCI, EuroQol, dementia, MoCA, S&E, NMSS Hallucinations, HY, and PIGD motor phenotype were significantly associated with mortality. Adjusting for age, gender and disease duration, S&E remained significantly associated with mortality. In multivariate logistic regression analysis, death was significantly associated with disease duration, CCI and NMSS-mood/cognition scores. PD was not associated with an excess of mortality, but conferred a higher probability of dying from pneumonia. Comorbidity was a major determinant, but disease duration, baseline incapacity, cognition, psychosis, mood complaints and HRQL also contributed significantly to mortality.

Evidence of amyloid-ß cerebral amyloid angiopathy transmission through neurosurgery.

Amyloid-ß (Aß) is a peptide deposited in the brain parenchyma in Alzheimer's disease and in cerebral blood vessels, causing cerebral amyloid angiopathy (CAA). Aß pathology is transmissible experimentally in animals and through medical procedures in humans, such as contaminated growth hormone or dura mater transplantation in the context of iatrogenic prion disease. Here, we present four patients who underwent neurosurgical procedures during childhood or teenage years and presented with intracerebral haemorrhage approximately three decades later, caused by severe CAA. None of these patients carried pathogenic mutations associated with early Aß pathology development. In addition, we identified in the literature four patients with a history of neurosurgical intervention and subsequent development of CAA. These findings raise the possibility that Aß pathology may be transmissible, as prion disease is, through neurosurgical procedures.

Electron Paramagnetic Resonance and Small-Angle X-ray Scattering Characterization of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Dibucaine Encapsulation.

Dibucaine (DBC) is one of the most potent long-acting local anesthetics, but it also has significant toxic side effects and low water solubility. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have been proposed as drug-delivery systems to increase the bioavailability of local anesthetics. The purpose of the present study was to characterize SLNs and NLCs composed of cetyl palmitate or myristyl myristate, a mixture of capric and caprylic acids (for NLCs only) plus Pluronic F68 prepared for the encapsulation of DBC. We intended to provide a careful structural characterization of the nanoparticles to identify the relevant architectural parameters that lead to the desirable biological response. Initially, SLNs and NLCs were assessed in terms of their size distribution, morphology, surface charge, and drug loading. Spectroscopic techniques (infrared spectroscopy and electron paramagnetic resonance, EPR) plus small-angle X-ray scattering (SAXS) provided information on the interactions between nanoparticle components and their structural organization. The sizes of nanoparticles were in the 180 nm range with low polydispersity and negative zeta values (-25 to -46 mV). The partition coefficient of DBC between nanoparticles and water at pH 8.2 was very high (>104). EPR (with doxyl-stearate spin labels) data revealed the existence of lamellar arrangements inside the lipid nanoparticles, which was also confirmed by SAXS experiments. Moreover, the addition of DBC increased the molecular packing of both SLN and NLC lipids, indicative of DBC insertion between the lipids, in the milieu assessed by spin labels. Such structural information brings insights into understanding the molecular organization of these versatile drug-delivery systems which have already demonstrated their potential for therapeutic applications in pain control.

Heart rate variability in Parkinson disease and idiopathic REM sleep behavior disorder.

PURPOSE: Heart rate variability, a marker of autonomic function modulation, is known to be blunted in Parkinson disease, although data remains conflicting and a putative modifying role of REM sleep behavior disorder persists unclarified. METHODS: We assessed ten patients with idiopathic REM sleep behavior disorder patients, 18 patients with Parkinson disease and REM behavior disorder and eight patients with Parkinson disease without REM sleep behavior disorder. Heart rate variability analysis was performed in 5-min epochs selected from wake, Non-REM and REM polysomnography records. We compared heart rate variability measures by stage between two sets of groups: Parkinson disease vs. idiopathic RBD and patients with vs. without RBD, by using repeated measures ANOVA. RESULTS: There were no heart rate variability differences between Parkinson disease and idiopathic REM sleep behavior disorder groups. There were significant stage vs. group interactions (p = 0.045) regarding the high frequencies components when comparing patients with and without REM sleep behavior disorder, with the former presenting lower values and attenuation of sleep stage variations. CONCLUSION: Our study suggests that RBD is related with reduction in parasympathetic modulation of heart rate variability and blunting of sleep stage related variations.

The Influence of Menopause in Multiple Sclerosis Course: A Longitudinal Cohort Study.

BACKGROUND: Hormonal variations are known to influence the course of multiple sclerosis (MS). OBJECTIVES: We aimed to evaluate the impact of menopause in MS course, including disease activity and disability progression. METHODS: We conducted a retrospective longitudinal cohort study including all women, older than 44, post-menopausal, with a diagnosis of MS at least 1 year before menopause. We evaluated the impact of menopause in MS course comparing clinical and radiologic outcomes within 5 years before and after menopause. We repeated the analysis in subgroups of patients without disease-modifying treatment (DMT) change or co-morbidities diagnosed during the observation period, considering that those factors might also impact MS outcomes. RESULTS: Thirty-seven women, with a mean age at the time of menopause of 49.8 (±4.06) years were included in the analysis. Within 5 years following menopause, we observed a decrease in the annualized relapse rate (0.37 ± 0.35 pre-menopause vs. 0.08 ± 0.18 post-menopause, p < 0.001) compared with the same period before menopause, while the EDSS progression rate remained stable (0.13 ± 0.24 EDSS point/year pre-menopausal vs. 0.13 ± 0.18 post-menopause, p = 0.935). EDSS progression events frequency was similar before and after the menopause (37.8 vs. 48.6%, respectively, p = 0.424). These observations persisted in patients' subgroups without DMT switch or co-morbidities. CONCLUSIONS: Following menopause, we observed a reduction in the relapse rate, but the disability progression continued at a similar rate, compared to the pre-menopausal period. These observations persisted in the subgroup of patients without changes in DMT or co-morbidities diagnosed during the observation period.

Development of solid dispersions of ß-lapachone in PEG and PVP by solvent evaporation method.

ß-lapachone (ßlap) has shown potential use in various medical applications. However, its poor solubility has limited its systemic administration and clinical applications. The aim of this work is to develop solid dispersions of ßlap using poly (ethylene glycol) (PEG 6000) and polyvinylpyrrolidone (PVP K30) as hydrophilic polymers and evaluate the dissolution rate in aqueous medium. Solid dispersions were prepared by solvent evaporation method using different weight ratios of ßlap and hydrophilic polymer (1:1, 1:2, and 1:3). Characterization performed by differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy showed that ßlap was molecularly dispersed within the polymer matrix. The in vitro dissolution tests showed an enhancement in the dissolution profile of ßlap as solid dispersions prepared in both PVP and PEG, although the former showed better results. The drug:polymer ratio influenced ßlap dissolution rate, as higher amounts of hydrophilic polymer led to enhanced drug dissolution. Thus, this study demonstrated that solid dispersions of ßlap in PVP offers an effective way to overcome the poor dissolution of ßlap.