Artigos e Materiais de Revistas Científicas - LIM/40

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A coleção de Artigos e Materiais de Revistas Científicas engloba artigos originais, artigos de revisão, artigos de atualização, artigos técnicos, relatos de experiências, resenhas, ensaios, editoriais, cartas ao editor, debates, notas científicas e técnicas, depoimentos, entrevistas e pontos de vista. Consideram-se como artigos científicos originais os trabalhos redigidos para divulgação de informações e resultados sobre determinada pesquisa científica, publicados em periódico científico após avaliação por outros pesquisadores.

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Data-driven, cross-disciplinary collaboration: lessons learned at the largest academic health center in Latin America during the COVID-19 pandemic
(2024) RITTO, Ana Paula; ARAUJO, Adriana Ladeira de; CARVALHO, Carlos Roberto Ribeiro de; SOUZA, Heraldo Possolo De; FAVARETTO, Patricia Manga e Silva; SABOYA, Vivian Renata Boldrim; GARCIA, Michelle Louvaes; KULIKOWSKI, Leslie Domenici; KALLAS, Esper Georges; PEREIRA, Antonio Jose Rodrigues; COBELLO JUNIOR, Vilson; SILVA, Katia Regina; ABDALLA, Eidi Raquel Franco; SEGURADO, Aluisio Augusto Cotrim; SABINO, Ester Cerdeira; RIBEIRO JUNIOR, Ulysses; FRANCISCO, Rossana Pulcineli Vieira; MIETHKE-MORAIS, Anna; LEVIN, Anna Sara Shafferman; SAWAMURA, Marcio Valente Yamada; FERREIRA, Juliana Carvalho; SILVA, Clovis Artur; MAUAD, Thais; GOUVEIA, Nelson da Cruz; LETAIF, Leila Suemi Harima; BEGO, Marco Antonio; BATTISTELLA, Linamara Rizzo; DUARTE, Alberto Jose da Silva; SEELAENDER, Marilia Cerqueira Leite; MARCHINI, Julio; FORLENZA, Orestes Vicente; ROCHA, Vanderson Geraldo; MENDES-CORREA, Maria Cassia; COSTA, Silvia Figueiredo; CERRI, Giovanni Guido; BONFA, Eloisa Silva Dutra de Oliveira; CHAMMAS, Roger; BARROS FILHO, Tarcisio Eloy Pessoa de; BUSATTO FILHO, Geraldo
Introduction The COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency.Methods At the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank. Additionally, a COVID-19 curated collection was created within the institutional digital library of academic papers to map the research output.Results Over the course of the experience, the possible benefits and challenges of this type of research support approach were identified and discussed, leading to a set of recommended strategies to enhance collaboration within the research institution. Demographic and clinical data from COVID-19 hospitalizations were compiled in a database including adults and a minority of children and adolescents with laboratory confirmed COVID-19, covering 2020-2022, with approximately 350 fields per patient. To date, this database has been used in 16 published studies. Additionally, we assessed 700 adults 6 to 11 months after hospitalization through comprehensive, multidisciplinary in-person evaluations; this database, comprising around 2000 fields per subject, was used in 15 publications. Furthermore, thousands of blood samples collected during the acute phase and follow-up assessments remain stored for future investigations. To date, more than 3,700 aliquots have been used in ongoing research investigating various aspects of COVID-19. Lastly, the mapping of the overall research output revealed that between 2020 and 2022 our academic system produced 1,394 scientific articles on COVID-19.Discussion Research is a crucial component of an effective epidemic response, and the preparation process should include a well-defined plan for organizing and sharing resources. The initiatives described in the present paper were successful in our aim to foster large-scale research in our institution. Although a single model may not be appropriate for all contexts, cross-disciplinary collaboration and open data sharing should make health research systems more efficient to generate the best evidence.
Vocational Rehabilitation and Length of Stay at Work after Work-Related Musculoskeletal Disorders: A Longitudinal Study in Brazil
(2023) MIRANDA, C. B. de; SILVA-JUNIOR, J. S.; GARCIA, K. K. S.; SOUSA, F. N. E. F. de; FISCHER, F. M.
Vocational rehabilitation is an intervention to enhance the return to work and improve quality of life. The aim of this study was to evaluate sociodemographic and occupational factors associated with the length of stay at work among workers with work-related musculoskeletal disorders (WRMDs) who had undergone rehabilitation through the Brazilian public social security system. This was a longitudinal study among 680 workers with histories of disability due to WRMDs who returned to the formal job market after vocational rehabilitation between 2014 and 2018. Survival analysis was performed to identify the factors influencing permanence in work. Job dismissal occurred for 29.26% of the workers. The average duration of employment after returning to the formal job position was 56 months. The following factors were associated with shorter length of employment: living in the southeastern region (HR: 2.78; 95% CI 1.12–6.91) or southern region (HR: 2.68; 95% CI 1.04–6.90) of Brazil; working in transportation, storage or postal services (HR: 2.57; 95% CI 1.07–6.17); or working in financial activities, insurance or related services (HR: 2.70; 95% CI 1.05–6.89). These findings may contribute to the discussion about prevention of disability and interventions to ensure health care for workers with WRMD disabilities who undergo rehabilitation.
The concordance study of the portable camera FLIR C5 for detecting asymmetry of skin temperature in patients with stroke sequelae
(2023) ALFIERI, F. M.; SANTOS, A. C. A. dos; DIAS, C. da Silva; BATTISTELLA, L. R.
BACKGROUND: Low-cost portable infrared cameras are increasingly used for health assessments, especially for investigating the skin temperature of the whole body. However, some of these devices have not yet been tested for agreement with high-resolution cameras. Therefore, the objective of this study was to test the agreement of FLIR C5, a portable infrared thermographic camera, compared to the FLIR T650sc, a high-quality and high-resolution thermographic device, for detecting thermal asymmetry between both sides of the body of patients with motor sequelae after stroke. MATERIALS AND METHODS: This is an observational and cross-sectional study conducted in a physical rehabilitation facility with 14 patients with stroke sequelae. Participants had their temperature simultaneously measured by FLIR T650sc and FLIR C5 infrared thermography cameras and analyzed with the software FLIR Tools®. The temperature difference of each ROI measured by both cameras was compared with Lin's Concordance Correlation Coefficient (rho or ρc) and Bland Altman the limits of agreement (LOA). RESULTS: the temperatures measured by FLIR C5 were lower than those measured by FLIR T650sc, regardless of the region of interest or side (-0.65, SD 1.44). We observed that the general concordance was classified as adequate to excellent (ρc=0.859; 95%CI 0.817-0.901; p<0.001) and that the forearm and leg in the posterior view presented the sites with the best associations between the temperature readings of FLIR C5 and FLIR T650sc. CONCLUSIONS: The temperature asymmetry usually found among patients with stroke sequelae may be assessed by the portable infrared thermographic camera FLIR C5, given its suitable concordance with FLIR T650sc.
OPRM1 and BDNF polymorphisms associated with a compensatory neurophysiologic signature in knee osteoarthritis patients
(2023) GONCALVES, Fernanda de Toledo; MARQUES, Lucas Murrins; PESSOTTO, Anne Victorio; BARBOSA, Sara Pinto; IMAMURA, Marta; SIMIS, Marcel; FREGNI, Felipe; BATTISTELLA, Linamara
Objective: The present study investigated the relationship between three genetic polymor-phisms of OPRM1 (rs1799971 -A118G and rs1799972 -C17T) and BDNF (rs6265 -C196T) and EEG-measured brain oscillations in Knee Osteoarthritis (KOA) patients.Materials and Methods: We performed a cross-sectional analysis of a cohort study (DEFINE cohort), KOA arm, with 66 patients, considering demographic (age, sex, and education), clinical (pain intensity and duration), OPRM1 (rs1799971 -A118G and rs1799972 -C17T) and BDNF (rs6265 -C196T) genotypes, and electrophysiological measures. Brain oscillations relative power from Delta, Theta, Alpha, Low Alpha, High Alpha, Beta, Low Beta and High Beta oscillations were measured during resting state EEG. Multivariate regression models were used to explore the main brain oscillation predictors of the three genetic polymorphisms.Results: Our findings demonstrate that Theta and Low Beta oscillations are associated with the variant allele of OPRM1-rs1799971 (A118G) on left frontal and left central regions, respectively, while Alpha brain oscillation is associated with variant genotypes (CT/TT) of BDNF-rs6265 on frontal (decrease of oscillation power) and left central (increase of oscillation power) regions. No significant model was found for OPRM1-rs1799972 (C17T) in addition to the inclusion of pain intensity as a significant predictor of this last model.Conclusion: One potential interpretation for these findings is that polymorphisms of OPRM1 that is involved with endogenous pain control lead to increased compensatory oscillatory mechanisms, characterized by increased theta oscillations. Along the same line, polymorphisms of the BDNF lead to decreased alpha oscillations in the frontal area, likely also reflecting the disruption of resting states to also compensate for the increased injury associated with knee OA. It is possible that these polymorphisms require additional brain adaption to the knee OA related injury.(c) 2023 Published by Elsevier Masson SAS.
Robotic-Assisted Gait Training (RAGT) in Stroke Rehabilitation: A Pilot Study
(2023) NEVES, Mariana Vita Milazzotto; FURLAN, Leonardo; FREGNI, Felipe; BATTISTELLA, Linamara Rizzo; SIMIS, Marcel
Objective: To compare the effects of 2 types of robotic-assisted gait training (RAGT) devices that have been used in stroke rehabilitation. Design: Retrospective cohort.Setting: Rehabilitation hospital.Participants: 24 community dwelling people with stroke (N=24).Interventions: RAGT with either an exoskeleton (Lokomat) (mean age=53.8 years; 30% men; mean duration of stroke =17.8 months) or an end-effector (G-EO) (mean age=50.5 years; 77.8% men; mean duration of stroke =13.11) delivered 3 times per week (36 sessions total).Main Outcome Measures: The following tests/scales were employed before and after RAGT: Functional Ambulation Categories (FACs), timed Up and Go (TUG), 10-Meter Walk Test (10MWT), 6 -Minute Walk Test (6MWT), Trunk Impairment Scale, Dynamic Gait Index (DGI), Berg Balance Scale (BBS), and ability to climb stairs (time to climb 6 steps of 15 cm each; ability to climb stairs).Results: There were 5 dropouts, all from the G-EO group. At the end, 10 participants in the Lokomat and 9 in the G-EO group completed the intervention. From pre-to post-RAGT, G-EO patients improved on all functional tests/scales, whereas Lokomat patients improved only on the TUG, DGI, and BBS. Most patients showed improvements above the relative smallest real difference in the TUG, 10MWT, and 6MWT.Conclusions: Both end-effectors and exoskeletons may improve clinically relevant aspects of walking function. However, this study had a small sample, was retrospective, non-randomized, and had a significant number of drop-outs, therefore its findings should be interpreted carefully. Future studies are needed for investigating potential differences in clinical results, side effects, contraindications, and cost effectiveness between these 2 different types of RAGT.(c) 2023 The Authors.
EUS-guided choledochoduodenostomy for malignant biliary obstruction: A multicenter comparative study between plastic and metallic stents
(2023) SILVA, Rodrigo Roda Rodrigues da; FACANALI JUNIOR, Marcio Roberto; BRUNALDI, Vitor Ottoboni; OTOCH, Jose Pinhata; ROCHA, Ana Carolina Aguiar; ARTIFON, Everson Luiz de Almeida
Background and Objectives: EUS-guided choledochoduodenostomy (EUS-CDS) is commonly employed to address malignant biliary obstruction (MBO) after a failed ERCP. In this context, both self-expandable metallic stents (SEMSs) and double-pigtail stents (DPSs) are suitable devices. However, few data comparing the outcomes of SEMS and DPS exist. Therefore, we aimed to compare the efficacy and safety of SEMS and DPS at performing EUS-CDS. Methods: We conducted a multicenter retrospective cohort study between March 2014 and March 2019. Patients diagnosed with MBO were considered eligible after at least one failed ERCP attempt. Clinical success was defined as a drop of direct bilirubin levels >= 50% at 7 and 30 postprocedural days. Adverse events (AEs) were categorized as early (<= 7 days) or late (> 7 days). The severity of AEs was graded as mild, moderate, or severe. Results: Forty patients were included, 24 in the SEMS group and 16 in the DPS group. Demographic data were similar between the groups. Technical success rates and clinical success rates at 7 and 30 days were similar between the groups. Similarly, we found no statistical difference in the incidence of early or late AEs. However, there were two severe AEs (intracavitary migration) in the DPS group and none in the SEMS cohort. Finally, there was no difference in median survival (DPS 117 days vs. SEMS 217 days; P = 0.99). Conclusion: EUS-guided CDS is an excellent alternative to achieve biliary drainage after a failed ERCP for MBO. There is no significant difference regarding the effectiveness and safety of SEMS and DPS in this context.
Multiple TP53 p.R337H haplotypes and implications for tumor susceptibility
(2024) PINTO, Emilia M.; FRIDMAN, Cintia; FIGUEIREDO, Bonald C.; SALVADOR, Hector; TEIXEIRA, Manuel R.; PINTO, Carla; PINHEIRO, Manuela; KRATZ, Christian P.; LAVARINO, Cinzia; LEGAL, Edith A. M. F.; LE, Anh; KELLY, Gregory; KOEPPE, Erika; STOFFEL, Elena M.; BREEN, Kelsey; HAHNER, Stefanie; HEINZE, Britta; TECHAVICHIT, Piti; KRAUSE, Amanda; OGATA, Tsutomu; FUJISAWA, Yasuko; WALSH, Michael F.; RANA, Huma Q.; MAXWELL, Kara N.; GARBER, Judy E.; RODRIGUEZ-GALINDO, Carlos; RIBEIRO, Raul C.; ZAMBETTI, Gerard P.
The germline TP53 p.R337H mutation is reported as the most common germline TP53 variant. It exists at a remarkably high frequency in the population of southeast Brazil as founder mutation in two distinct haplotypes with the most frequent co-segregating with the p.E134* variant of the XAF1 tumor suppressor and an increased cancer risk. Founder mutations demonstrate linkage disequilibrium with neighboring genetic polymorphic markers that can be used to identify the founder variant in different geographic regions and diverse populations. We report here a shared haplotype among Brazilian, Portuguese, and Spanish families and the existence of three additional distinct TP53 p.R337H alleles. Mitochondrial DNA sequencing and Y-STR profiling of Brazilian carriers of the founder TP53 p.R337H allele reveal an excess of Native American haplogroups in maternal lineages and exclusively European haplogroups in paternal lineages, consistent with communities established through male European settlers with extensive intermarriage with Indigenous women. The identification of founder and independent TP53 p.R337H alleles underlines the importance for considering the haplo-type as a functional unit and the additive effects of constitutive polymorphisms and associated variants in modifier genes that can in-fluence the cancer phenotype.
A model for personalized diagnostics for non-specific low back pain: the role of the myofascial unit
(2023) SIKDAR, Siddhartha; SRBELY, John; SHAH, Jay; ASSEFA, Yonathan; STECCO, Antonio; DESTEFANO, Secili; IMAMURA, Marta; GERBER, Lynn H.
Low back pain (LBP) is the leading cause of disability worldwide. Most LBP is non-specific or idiopathic, which is defined as symptoms of unknown origin without a clear specific cause or pathology. Current guidelines for clinical evaluation are based on ruling out underlying serious medical conditions, but not on addressing underlying potential contributors to pain. Although efforts have been made to identify subgroups within this population based on response to treatment, a comprehensive framework to guide assessment is still lacking. In this paper, we propose a model for a personalized mechanism-based assessment based on the available evidence that seeks to identify the underlying pathologies that may initiate and perpetuate central sensitization associated with chronic non-specific low back pain (nsLBP). We propose that central sensitization can have downstream effects on the ""myofascial unit"", defined as an integrated anatomical and functional structure that includes muscle fibers, fascia (including endomysium, perimysium and epimysium) and its associated innervations (free nerve endings, muscle spindles), lymphatics, and blood vessels. The tissue-level abnormalities can be perpetuated through a vicious cycle of neurogenic inflammation, impaired fascial gliding, and interstitial inflammatory stasis that manifest as the clinical findings for nsLBP. We postulate that our proposed model offers biological plausibility for the complex spectrum of clinical findings, including tissue-level abnormalities, biomechanical dysfunction and postural asymmetry, ecological and psychosocial factors, associated with nsLBP. The model suggests a multi-domain evaluation that is personalized, feasible and helps rule out specific causes for back pain guiding clinically relevant management. It may also provide a roadmap for future research to elucidate mechanisms underlying this ubiquitous and complex problem.
Digital Platform for Continuous Monitoring of Patients Using a Smartwatch: Longitudinal Prospective Cohort Study
(2023) BIN, Kaio Jia; PRETTO, Lucas Ramos De; SANCHEZ, Fabio Beltrame; CASTRO, Fabio Pacheco Muniz De Souza e; RAMOS, Vinicius Delgado; BATTISTELLA, Linamara Rizzo
Background: Since the COVID-19 pandemic, there has been a boost in the digital transformation of the human society, where wearable devices such as a smartwatch can already measure vital signs in a continuous and naturalistic way; however, the security and privacy of personal data is a challenge to expanding the use of these data by health professionals in clinical follow-up for decision-making. Similar to the European General Data Protection Regulation, in Brazil, the Lei Geral de Protecao de Dados established rules and guidelines for the processing of personal data, including those used for patient care, such as those captured by smartwatches. Thus, in any telemonitoring scenario, there is a need to comply with rules and regulations, making this issue a challenge to overcome.Objective: This study aimed to build a digital solution model for capturing data from wearable devices and making them available in a safe and agile manner for clinical and research use, following current laws.Methods: A functional model was built following the Brazilian Lei Geral de Protecao de Dados (2018), where data captured by smartwatches can be transmitted anonymously over the Internet of Things and be identified later within the hospital. A total of 80 volunteers were selected for a 24-week follow-up clinical trial divided into 2 groups, one group with a previous diagnosis of COVID-19 and a control group without a previous diagnosis of COVID-19, to measure the synchronization rate of the platform with the devices and the accuracy and precision of the smartwatch in out-of-hospital conditions to simulate remote monitoring at home.Results: In a 35-week clinical trial, >11.2 million records were collected with no system downtime; 66% of continuous beats per minute were synchronized within 24 hours (79% within 2 days and 91% within a week). In the limit of agreement analysis, the mean differences in oxygen saturation, diastolic blood pressure, systolic blood pressure, and heart rate were -1.280% (SD 5.679%), -1.399 (SD 19.112) mm Hg, -1.536 (SD 24.244) mm Hg, and 0.566 (SD 3.114) beats per minute, respectively. Furthermore, there was no difference in the 2 study groups in terms of data analysis (neither using the smartwatch nor the gold-standard devices), but it is worth mentioning that all volunteers in the COVID-19 group were already cured of the infection and were highly functional in their daily work life.Conclusions: On the basis of the results obtained, considering the validation conditions of accuracy and precision and simulating an extrahospital use environment, the functional model built in this study is capable of capturing data from the smartwatch and anonymously providing it to health care services, where they can be treated according to the legislation and be used to support clinical decisions during remote monitoring.
Return to work after sick leave due to musculoskeletal disorder or injury: a longitudinal study conducted in Brazil
(2023) SILVA, Joao Silvestre; MARTINEZ, Maria Carmen; SEKIYA, Felipe Seiti; MIRANDA, Cristiano Barreto de; FISCHER, Frida Marina
BackgroundMusculoskeletal disorders and injuries (MSDI) are conditions that affect the locomotor system characterized by pain and impairment of functionality. They are the leading cause of years lived with disability. The aim of this study was to analyze the factors that influence the return to work (RTW) among workers on sick leave due to MSDI. MethodsA longitudinal study was conducted in the city of Sao Paulo, Brazil, between 2020-2022. The participants were 216 workers who required social security compensation due to MSDI. They filled out online questionnaires about their sociodemographic characteristics, health risk behaviors, work characteristics and health conditions. They were followed for 365 days after their first day of sick leave. A Cox regression was performed to identify the factors that influenced their first RTW.ResultsMost participants were male (53.0%), mean age was 39.5 years (SD 10.6), 70.4% returned to work within the one-year follow-up period. The mean duration of sick leave was 192.6 days. Factors associated with a lower RTW were age 40 years and older (HR 0.54; 95%CI 0.39-0.76) and the interaction between perceptions of the need for improvement in the physical and psychological domains of quality of life (HR 0.67; 95%CI 0.48-0.94).ConclusionsOccupational healthcare professionals should pay greater attention to patients who are aging and those with perceived worse physical and psychological conditions, in order to facilitate the reintegration process and promote sustained RTW after sick leave due to musculoskeletal disorder or injury.
Functional and Neural Correlates Associated with Conditioned Pain Modulation in Patients with Chronic Knee Osteoarthritis Pain: A Cross-Sectional Study
(2023) SIMIS, Marcel; PACHECO-BARRIOS, Kevin; VASQUEZ-AVILA, Karen; REBELLO-SANCHEZ, Ingrid; PARENTE, Joao; CASTELO-BRANCO, Luis; MARDUY, Anna; MELO, Paulo S. de; IMAMURA, Marta; BATTISTELLA, Linamara; FREGNI, Felipe
In this study, we aimed to assess the factors that predict a dysfunctional conditioned pain modulation (CPM) in chronic knee OA. Methods: This is a cross-sectional analysis of patients with chronic knee OA from a prospective cohort study in Brazil (n = 85). We performed linear and logistic multivariate regression models using the purposeful selection approach to test the relationship between the CPM in both knees (average) as a dependent variable and demographics, clinical, and neurophysiological as independent variables. Results: A significant negative association between WOMAC pain scores and CPM (beta: 0.13) was found. This association was modified by the subjects' race, being stronger in the non-white subjects. In our logistic regression models, pain intensity indexed with the WOMAC pain scale remained a significant association with dichotomized CPM. Furthermore, a significant CPM association with balance, indexed with the Berg Balance score, was evidenced ( beta: 0.04). Neurophysiological variables showed a significant negative relationship with CPM, such as the relative power of delta oscillations in the frontal area ( beta: 3.11) and central area ( beta: 3.23). There was no significant relationship between CPM and the following domains: cognitive, emotion, sleep, opioid receptor polymorphisms, and intrinsic variables of OA disease. There was no association of CPM with TMS-indexed inhibitory markers. Conclusions: These results may indicate that less function of the pain descending inhibitory system in patients with OA is correlated with higher activity-related pain (WOMAC), less balance, and cortical plasticity especially with increased low-frequency (delta) brain oscillations. These associations seem modified by race.
Analysis of genetic polymorphisms associated with the presence of freckles for phenotypic prediction
(2022) FRIDMAN, Cintia; FERREIRA, Marcelo Alves; MARANO, Leonardo Arduino; FORLENZA, Bettina Stingelin
The prediction of externally visible characteristics (EVCs) is a commonly used practice by the forensic sciences as an important resource in the investigation of criminal cases in which the identity of perpetrators or victims is unknown or even to recognize decomposed cadavers. With this purpose, genetic markers associated with pigmentation traits have been widely studied by forensic scientists and, nowadays, it is possible to predict phenotypic characteristics such as hair, eyes and skin colour, as well as the presence of skin freckles by analysing single nucleotide polymorphisms (SNPs). In this study, we analysed the association of six SNPs located in pigmentation genes to the presence of freckles in individuals from the Brazilian population for forensic DNA phenotyping. The study was based within the context of a larger project on a population sample of 534 adult Brazilians of both sexes and different skin colours. DNA was extracted from peripheral blood and genotyped using the TaqMan & REG; OpenArray & REG; Real-Time PCR System (ThermoFischer Scientific) technique. Statistical analyses were carried out with the R software (version 4.0.2). As for the results obtained, three SNPs were shown to be statistically associated to the freckling, rs12203592, rs1800404 and rs222847, with CT, AG and AA genotypes being the main contributors, respectively. Variables such as sex of the individuals and skin colour were found to also contribute to the manifestation of this pigmentation trait. Further statistical analyses will be carried out to evaluate the possibility of using the SNPs in this study for phenotyping prediction of the Brazilian population, improving existing DNA phenotyping models in forensic sciences.
Neurophysiological biomarkers of motor improvement from Constraint-Induced Movement Therapy and Robot-Assisted Therapy in participants with stroke
(2023) SIMIS, Marcel; THIBAUT, Aurore; IMAMURA, Marta; BATTISTELLA, Linamara Rizzo; FREGNI, Felipe
BackgroundThe mechanism of stroke recovery is related to the reorganization of cerebral activity that can be enhanced by rehabilitation therapy. Two well established treatments are Robot-Assisted Therapy (RT) and Constraint-Induced Movement Therapy (CIMT), however, it is unknown whether there is a difference in the neuroplastic changes induced by these therapies, and if the modifications are related to motor improvement. Therefore, this study aims to identify neurophysiological biomarkers related to motor improvement of participants with chronic stroke that received RT or CIMT, and to test whether there is a difference in neuronal changes induced by these two therapies.MethodsThis study included participants with chronic stroke that took part in a pilot experiment to compare CIMT vs. RT. Neurophysiological evaluations were performed with electroencephalography (EEG) and transcranial magnetic stimulation (TMS), pre and post rehabilitation therapy. Motor function was measured by the Wolf Motor Function Test (WMFT) and Fugl-Meyer Assessment Upper Limb (FMA-UL).ResultsTwenty-seven participants with chronic stroke completed the present study [mean age of 58.8 years (SD +/- 13.6), mean time since stroke of 18.2 months (SD +/- 9.6)]. We found that changes in motor threshold (MT) and motor evoked potential (MEP) in the lesioned hemisphere have a positive and negative correlation with WMFT improvement, respectively. The absolute change in alpha peak in the unlesioned hemisphere and the absolute change of the alpha ratio (unlesioned/lesioned hemisphere) is negatively correlated with WMFT improvement. The decrease of EEG power ratio (increase in the lesioned hemisphere and decrease in the unlesioned hemisphere) for high alpha bandwidths is correlated with better improvement in WMFT. The variable ""type of treatment (RT or CIMT)"" was not significant in the models.ConclusionOur results suggest that distinct treatments (RT and CIMT) have similar neuroplastic mechanisms of recovery. Moreover, motor improvements in participants with chronic stroke are related to decreases of cortical excitability in the lesioned hemisphere measured with TMS. Furthermore, the balance of both EEG power and EEG alpha peak frequency in the lesioned hemisphere is related to motor improvement.
Motor event-related synchronization as an inhibitory biomarker of pain severity, sensitivity, and chronicity in patients with knee osteoarthritis
(2022) MARQUES, L. M.; BARBOSA, S. P.; PACHECO-BARRIOS, K.; GONCALVES, F. T.; IMAMURA, M.; BATTISTELLA, L. R.; SIMIS, M.; FREGNI, F.
Objective: The study aimed to examine the clinical and neurophysiological predictors of motor event-related desynchronization (ERD) and synchronization (ERS) in patients with chronic pain due to knee osteoarthritis (KOA). Methods: We performed a cross-sectional analysis of our cohort study (DEFINE cohort), KOA arm, with 71 patients, including demographic, functionality, genetic and neurophysiological measures. ERD/ERS was evaluated during hand motor tasks (motor execution, active and passive observation, and imagery). Multivariate regression models were used to explore predictors of ERD/ERS. Results: Although we found an altered ERD/ERS pattern during motor execution and active observation, the ERS pattern could only be clearly differentiated after passive observation.‘. We found no predictors of ERD (excitatory biomarker). For ERS (inhibitory biomarker), our results showed that the main predictors differ across EEG frequency bands. Considering pain measures, we found that visual analogue scale (VAS, right knee) and chronicity of pain negatively predict low beta and high beta ERS, respectively. Pain threshold was positively correlated with alpha ERS, while 36-Item Short Form Survey (SF-36) emotional domain positively predicted beta ERS. Regarding transcranial magnetic stimulation (TMS) markers, intracortical inhibition (ICF) negatively predicted beta and low beta ERS, and left hemisphere cortical silent period (CSP) negatively predicted low beta ERS. Conclusion: Considering that higher power of ERS indicates a stronger cortical organization and inhibitory drive, our results show that limitation of activities due to emotional factors, lower pain threshold, higher VAS pain, and longer duration of pain are associated with lower ERS power (in alpha and beta frequencies), thus indicating a lower inhibitory drive. In the same direction, a lower inhibitory drive as indicated by higher ERS power is associated with higher ICF amplitude. Although there was a negative association between ERS and CSP, this may indicate that ICF values are adjusting CSP results. Our findings support the idea that a less organized cortical response as indicated by changes to the ERS is associated with higher pain correlates in subjects with KOA. © 2022
Motor Cortex Inhibition and Facilitation Correlates with Fibromyalgia Compensatory Mechanisms and Pain: A Cross-Sectional Study
(2023) PACHECO-BARRIOS, Kevin; PIMENTA, Danielle Carolina; PESSOTTO, Anne Victorio; FREGNI, Felipe
The role of transcranial magnetic stimulation (TMS) measures as biomarkers of fibromyalgia syndrome (FMS) phenotypes is still unclear. We aimed to determine the clinical correlates of TMS measures in FMS patients. We conducted a cross-sectional analysis that included 58 patients. We performed standardized TMS assessments, including resting motor threshold (MT), motor-evoked potential (MEP), short intracortical inhibition (SICI), and intracortical facilitation (ICF). Sociodemographic, clinical questionnaires, and quantitative sensory testing were collected from all of the patients. Univariate and multivariate linear regression models were built to explore TMS-associated factors. We found that SICI did not significantly correlate with pain levels but was associated with sleepiness, comorbidities, disease duration, and anxiety. On the other hand, ICF showed a positive correlation with pain levels and a negative correlation with body mass index (BMI). BMI was a negative effect modifier of the ICF and pain association. The clinical correlates of MT and MEP were scarce. Our results suggest that SICI and ICF metrics are potential phenotyping biomarkers in FMS related to disease compensation and levels of pain perception, respectively. The clinical translation of TMS paired-pulse protocols represents an opportunity for a mechanistic understanding of FMS and the future development of precision treatments.
Toxicity of Synthetic Cannabinoids in K2/Spice: A Systematic Review
(2023) OLIVEIRA, Mariana Campello de; VIDES, Mariana Capelo; LASSI, Dangela Layne Silva; TORALES, Julio; VENTRIGLIO, Antonio; BOMBANA, Henrique Silva; LEYTON, Vilma; PERICO, Cintia de Azevedo-Marques; NEGRAO, Andre Brooking; MALBERGIER, Andre; CASTALDELLI-MAIA, Joao Mauricio
(1) Background: Synthetic cannabinoids (SCs) are emerging drugs of abuse sold as 'K2', 'K9' or 'Spice'. Evidence shows that using SCs products leads to greater health risks than cannabis. They have been associated with greater toxicity and higher addiction potential unrelated to the primary psychoactive component of marijuana, & UDelta;9-tetrahydrocannabinol (& UDelta;9-THC). Moreover, early cases of intoxication and death related to SCs highlight the inherent danger that may accompany the use of these substances. However, there is limited knowledge of the toxicology of Spice ingredients. This systematic review intends to analyze the toxicity of SCs compounds in Spice/K2 drugs. (2) Methods: Studies analyzing synthetic cannabinoid toxicity and dependence were included in the present review. We searched the PubMed database of the US National Library of Medicine, Google Scholar, CompTox Chemicals, and Web of Science up to May 2022. (3) Results: Sixty-four articles reporting the effects of synthetic cannabinoids in humans were included in our review. Ten original papers and fifty-four case studies were also included. Fourteen studies reported death associated with synthetic cannabinoid use, with AB-CHMINACA and MDMB-CHMICA being the main reported SCs. Tachycardia and seizures were the most common toxicity symptoms. The prevalence of neuropsychiatric symptoms was higher in third-generation SCs. (4) Conclusion: SCs may exhibit higher toxicity than THC and longer-lasting effects. Their use may be harmful, especially in people with epilepsy and schizophrenia, because of the increased risk of the precipitation of psychiatric and neurologic disorders. Compared to other drugs, SCs have a higher potential to trigger a convulsive crisis, a decline in consciousness, and hemodynamic changes. Therefore, it is crucial to clarify their potential harms and increase the availability of toxicology data in both clinical and research settings.
Perspective on the use of investigative genetic genealogy in Brazil
(2022) BONAMIN, Pedro H. C.; MEDEIROS, Carlos E. M.; FRIDMAN, Cintia
Since 2018, investigative genetic genealogy (IGG) has been used as a novel technology to solve cold cases. But IGG presents several ethical issues regarding privacy and regulation. IGG has never been used in Brazil although the number of direct-to-consumer (DTC) ancestry tests has been increasing and its users use open platforms in which IGG can be applied, such as GEDMatch, being susceptible to the same ethical problems as in those countries where IGG is being applied. We conducted an online survey with 166 clients of DTC ancestry tests (DTC) and 35 Brazilian CODIS Administrators (ADM) to evaluate their knowledge about the forensic application of genetic genealogy, their opinion about it, and a possible application in Brazil. Both groups support using IGG in violent crimes and missing persons (58.5% of DTC and 34.3% of ADM) but also showed concerns about the legislation and ethical issues (78.9-55.4% DTC and 97-65% ADM). Furthermore, 20% of ADM were against the use of this technique compared to the DTC (4%), probably due to the lack of knowledge of the methodology, its scope, and limitations. These results show the need to broaden the discussion on the IGG in various sectors of society.
Analysis of isoalleles and flanking SNPs of STR markers by NGS to distinguish monozygotic twins
(2022) FONSECA, Renata I. B.; FRIDMAN, Cintia
DNA analysis for forensic investigations is based on the concept that everyone is genetically unique, except in cases of monozygotic (MZ) twins. The most used markers are STRs, analyzed by CE, but they don't allow the differentiation of MZ twins. Human identification using NGS is already part of some forensic laboratories and it enables reading the STRs' sequence and its isoalleles, but there is no reference to this application for differen-tiation of MZ twins. Herein, we evaluated the possibility to distinguish MZ using the Precision ID GlobalFilerTM NGS STR Panel v2. The CE and NGS profiles were compared for 16 pairs of MZ, and the allele results were concordant, except for one pair, which showed an allele dropout on Penta D, probably because of its low coverage. We observed isoalleles in both individuals of 3 pairs, each in a different marker: D2S441, D12S391, and D4S2408, respectively, which did not allow the differentiation within each pair. However, we observed 2 flanking SNPs, each one in a pair, in only one individual of the pair: rs560609904 in TPOX (G016A) and rs569521603 in D6S1043 (G027B), highlighting the possibility of differentiating MZ twins.
Health-related quality of life and functionality in primary caregiver of surviving pediatric COVID-19
(2023) MARTINS, Fernanda; GONCALVES, Fernanda T.; IMAMURA, Marta; BARBOZA, Daniela S.; MATHEUS, Denise; PEREIRA, Maria Fernanda B.; MARQUES, Heloisa H. S.; CORREA-SILVA, Simone; MONTENEGRO, Marilia M.; FINK, Thais T.; LINDOSO, Livia; BAIN, Vera; FERREIRA, Juliana C. O. A.; ASTLEY, Camilla; MATSUO, Olivia M.; SUGUITA, Priscila; TRINDADE, Vitor; PAULA, Camila S. Y.; LITVINOV, Nadia; PALMEIRA, Patricia; GUALANO, Bruno; DELGADO, Artur F.; CARNEIRO-SAMPAIO, Magda; FORSAIT, Silvana; ODONE-FILHO, Vicente; ANTONANGELO, Leila; BATTISTELLA, Linamara R.; SILVA, Clovis A.
ObjectivesTo prospectively assess health-related quality of life (HRQoL), global functionality, and disability in primary caregivers of surviving children and adolescents after COVID-19. MethodsA longitudinal observational study was carried out on primary caregivers of surviving pediatric post-COVID-19 patients (n = 51) and subjects without COVID-19 (n = 60). EuroQol five-dimension five-level questionnaire (EQ-5D-5L) and 12-question WHO Disability Assessment Schedule 2.0 (WHODAS 2.0) were answered for both groups. The univariate regression analysis was carried out using SPSS (v 20) and significance was established at 5%. ResultsThe median duration between COVID-19 diagnosis in children and adolescents and longitudinal follow-up visits was 4.4 months (0.8-10.7). The median age of children and adolescents caregivers with laboratory-confirmed COVID-19 was similar to primary caregivers of subjects without laboratory-confirmed COVID-19 [43.2 (31.6-60.9) vs. 41.5 (21.6-54.8) years, p = 0.08], as well as similar female sex (p = 1.00), level of schooling (p = 0.11), social assistance program (p = 0.28), family income/month U$ (p = 0.25) and the number of household's members in the residence (p = 0.68). The frequency of slight to extreme problems (level & GE; 2) of the pain/discomfort domain according to EQ-5D-5L score was significantly higher in the former group [74% vs. 52.5%, p = 0.03, OR = 2.57 (1.14-5.96)]. The frequency of disability according to WHODAS 2.0 total score was similar to those without disability and unknown (p = 0.79); however, with a very high disability in both groups (72.5% and 78.3%). Further analysis of primary caregivers of children and adolescents with post-COVID-19 condition (PCC) [n = 12/51 (23%)] compared to those without PCC [n = 39/51(77%)] revealed no differences between demographic data, EQ-5D-5L and WHODAS 2.0 scores in both groups (p > 0.05). ConclusionWe longitudinally demonstrated that pain/discomfort were predominantly reported in approximately 75% of primary caregiver of COVID-19 patients, with high disability in approximately three-quarters of both caregiver groups. These data emphasized the prospective and systematic caregiver burden evaluation relevance of pediatric COVID-19.
Economic analysis of antenatal screening for human T-cell lymphotropic virus type 1 in Brazil: an open access cost-utility model
(2023) ROSADAS, Carolina; SENNA, Katia; COSTA, Milene da; ASSONE, Tatiane; CASSEB, Jorge; NUKUI, Youko; COOK, Lucy; MARIANO, Livia; CASTRO, Bernardo Galvao; GRASSI, Maria Fernanda Rios; OLIVEIRA, Augusto Cesar Penalva de; CATERINO-DE-ARAUJO, Adele; MALIK, Bassit; BOA-SORTE, Ney; PEIXOTO, Paula; PUCCIONI-SOHLER, Marzia; SANTOS, Marisa; TAYLOR, Graham Philip
Background Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes severe diseases, such as aggressive cancer or progressive neurological disease. HTLV-1 affects mainly people in areas with low human development index and can be transmitted from mother to child, primarily through breastfeeding. Refraining from breastfeeding is an effective intervention to reduce the risk of infection in infants. However, HTLV-1 antenatal screening is not offered globally. According to WHO, the scarcity of cost-effectiveness studies is considered one of the major barriers to the implementation of policies to prevent HTLV-1 infection. Therefore, this study aimed to assess the cost-effectiveness of antenatal screening and postnatal interventions to prevent HTLV-1 mother-to-child transmission in Brazil and to develop an open-access, editable, mathematical model that can be used by other countries and regions to assess different scenarios. Methods In this cost-utility analysis, we constructed a decision tree and a Markov model to assess the cost-effectiveness of HTLV-1 antenatal screening and postnatal interventions (ie, avoidance of breastfeeding, by suppression of lactation with cabergoline, and provision of formula feed) to reduce transmission. For our model, we used data from Brazil and we took the perspective of the public health-care system to estimate costs. Findings The implementation of both screening and interventions would result in the prevention of 1039 infections in infants every year in Brazil with an incremental cost-effectiveness ratio (ICER) of US$11 415 per quality-adjusted lifeyear (QALY). 88% of all probabilistic sensitivity analysis simulations had ICER values lower than the Brazilian costeffectiveness threshold ($18 107 center dot 74 per QALY). HTLV-1 prevalence in pregnant women, the risk of HTLV-1 transmission when breastfeeding lasts for 6 months or more, and the cost of screening tests were the variables with the largest effect on ICER. Interpretation HTLV-1 antenatal screening is cost-effective in Brazil. An open-access model was developed, and this tool could be used to assess the cost-effectiveness of such policy globally, favouring the implementation of interventions to prevent HTLV-1 mother-to-child transmission worldwide.

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