ABSTRACT
Background:
Increasing numbers of mutations causing monogenic forms of Parkinson's disease (PD) have been described, mostly among patients in Europe and North America. Since genetic ...architecture varies between different populations, studying the specific genetic profile of Brazilian patients is essential for improving genetic counseling and for selecting patients for clinical trials.
Objective:
We conducted a systematic review to identify genetic studies on Brazilian patients and to set a background for future studies on monogenic forms of PD in Brazil.
Methods:
We searched MEDLINE, EMBASE and Web of Science from inception to December 2019 using terms for "Parkinson's disease", "genetics" and "Brazil". Two independent reviewers extracted the data. For the genes
LRRK2
and
PRKN
, the estimated prevalence was calculated for each study, and a meta-analysis was performed.
Results:
A total of 32 studies were included, comprising 94 Brazilian patients with PD with a causative mutation, identified from among 2,872 screened patients (3.2%).
PRKN
mutations were causative of PD in 48 patients out of 576 (8.3%).
LRRK2
mutations were identified in 40 out of 1,556 patients (2.5%), and p.G2019S was the most common mutation (2.2%).
Conclusions:
PRKN
is the most common autosomal recessive cause of PD, and
LRRK2
is the most common autosomal dominant form. We observed that there was a lack of robust epidemiological studies on PD genetics in Brazil and, especially, that the diversity of Brazil’s population had not been considered.
To evaluate the impact of COVID-19 on clinical and surgical practice, educational activities, health and lifestyle behavior of Brazilian urology residents.
A web-based survey was sent to 468 ...Brazilian urology residents from postgraduate years (PGY) 3 to 5 to collect data on clinical practice and training after 4 months of COVID-19. We also assessed health-related and behavior changes, rate of infection by SARS-CoV-2, deployment to the front line of COVID-19, residents' concerns, and access to personal protective equipment (PPE).
Massive reductions in elective and emergency patient consultations, diagnostic procedures and surgeries were reported across the country, affecting PGY 3 to 5 alike. Most in-person educational activities were abolished. The median damage to the urological training expected for 2020 was 6.0 3.4 -7.7, on a scale from 0 to 10, with senior residents estimating a greater damage (P < 0.001). Educational interventions developed included online case-based discussions, subspeciality conferences and lectures, and grand rounds. Most senior residents favored extending residency to compensate for training loss and most younger residents favored no additional training (p< 0.001). Modifications in health and lifestyle included weight gain (43.8%), reduced physical activity (68.6%), increased alcoholic intake (44.9%) and cigarette consumption (53.6%), worsening of sexual life (25.2%) and feelings of sadness or depression (48,2%). Almost half were summoned to work on the COVID-19 front-line and 24.4% had COVID-19. Most residents had inadequate training to deal with COVID-19 patients and most reported a shortage of PPE. Residents' concerns included the risk of contaminating family members, being away from residency program, developing severe COVID-19 and overloading colleagues.
COVID-19 had a massive impact in Brazilian urology residents´ training, health and lifestyle behavior, which may reflect what happened in other medical specialties. Studies should confirm these findings to help developing strategies to mitigate residents' losses.
Ant species (Hymenoptera, Formicidae) from the seasonally dry tropical forest of northeastern Brazil: a compilation from field surveys in Bahia and literature records. The Caatingas occur ...predominantly in northeastern Brazil and comparatively it is the biome that received less attention than any other ecosystem in Brazil, representing the region where invertebrate groups are less known. We present here the first list of ant species of the Caatingas, compiling information from the literature, from a study of samples preserved in alcohol in the Laboratory of Entomology (Universidade Estadual de Feira de Santana), and from a field survey conducted in Milagres, Bahia, submitting standardized 1-m² samples of the leaf-litter to Winkler extractors. Summing all information, 11 subfamilies, 61 genera and 173 species (plus one subspecies) of ants are recognized in the biome. This species number does not consider morphospecies that could not be named due to the lack of reliable recent taxonomic information for some Neotropical ant genera. The list presented here for ant species of the Caatingas is therefore underestimated, but it is relevant because it allows the identification of areas to be sampled in order to improve our knowledge of the diversity of ants in this biome.
The design and synthesis of artificial receptors based on molecular imprinting (MI) technology for the development of a new MIP-based biosensor for detection of the stress biomarker α-amylase in ...human saliva in point-of-care (PoC) applications is described in this work. The portable electrochemical devices for monitoring α-amylase consists of cost-effective and disposable gold screen-printed electrodes (AuSPEs). To build the electrochemical device, the template biomolecule was firstly immobilized directly over the working area of the gold chip previously activated with a self-assembled monolayer (SAM) of cysteamine (CA). Then, pyrrole (Py) monomer was selected as building block of a polymeric network prepared by CV electropolymerization. After the electropolymerization process, the enzyme was removed from the polymer film in order to build the specific recognition sites for the target enzyme. The MIP biosensor showed a very wide linear concentration range (between 3.0 × 10−4 to 0.60 mg mL−1 in buffer solution and between 3.0 × 10−4 to 3.0 × 10−2 mg mL−1 in human saliva) and low detection levels were achieved (LOD < 3.0 × 10−4 mg mL−1) using square wave voltammetry (SWV) as the electroanalytical technique.
Abstract Background Prostate cancer (PrCa) is the most frequently diagnosed cancer in men. Variants in known moderate- to high-penetrance genes explain less than 5% of the cases arising at ...early-onset (< 56 years) and/or with familial aggregation of the disease. Considering that BubR1 is an essential component of the mitotic spindle assembly checkpoint, we hypothesized that monoallelic BUB1B variants could be sufficient to fuel chromosomal instability (CIN), potentially triggering (prostate) carcinogenesis. Methods To unveil BUB1B as a new PrCa predisposing gene, we performed targeted next-generation sequencing in germline DNA from 462 early-onset/familial PrCa patients and 1,416 cancer patients fulfilling criteria for genetic testing for other hereditary cancer syndromes. To explore the pan -cancer role of BUB1B , we used in silico BubR1 molecular modeling, in vitro gene-editing, and ex vivo patients’ tumors and peripheral blood lymphocytes. Results Rare BUB1B variants were found in ~ 1.9% of the early-onset/familial PrCa cases and in ~ 0.6% of other cancer patients fulfilling criteria for hereditary disease. We further show that BUB1B variants lead to decreased BubR1 expression and/or stability, which promotes increased premature chromatid separation and, consequently, triggers CIN, driving resistance to Taxol-based therapies. Conclusions Our study shows that different BUB1B variants may uncover a trigger for CIN-driven carcinogenesis, supporting the role of BUB1B as a ( pan )-cancer predisposing gene with potential impact on genetic counseling and treatment decision-making.
Patients with rheumatoid arthritis (RA) have different presentations and prognoses. Cluster analysis based on proteomic signatures creates independent phenogroups of patients with different ...pathophysiological backgrounds. We aimed to identify distinct pathophysiological clusters of RA patients based on circulating proteomic biomarkers.
This was a cohort study including 399 RA patients. Clustering was performed on 94 circulating proteins (92 CVDII Olink®, high-sensitivity troponin T, and C-reactive protein). Unsupervised clustering was performed using a partitioning cluster algorithm.
The clustering algorithm identified two distinct clusters: cluster 1 (n = 223) and cluster 2 (n = 176). Compared with cluster 1, cluster 2 included older patients with a higher burden of comorbidities (cardiovascular and RA related), more erosive and longer RA duration, more dyspnoea and fatigue, walking a shorter distance in the Six-Minute Walk Test, with more severe diastolic dysfunction, and a 4.5-fold higher risk of death or hospitalization for cardiovascular reasons. Tumour necrosis factor (TNF) receptor superfamily-related pathways were mainly responsible for the model's discriminative ability.
Using unsupervised cluster analysis based on proteomic phenotypes, we identified two clusters of RA patients with distinct biomarkers profiles, clinical characteristics, and different outcomes that could reflect different pathophysiological backgrounds. TNF receptor superfamily-related proteins may be used to distinguish subgroups.
Cellulose nanofibers (CNFs) are natural polymers with physical-chemical properties that make them very attractive for modulating stem cell differentiation, a crucial step in tissue engineering and ...regenerative medicine. Although cellulose is cytocompatible, when materials are in nanoscale, they become more reactive, needing to evaluate its potential toxic effect to ensure safe application. This study aimed to investigate the cytocompatibility of cotton CNF and its differentiation capacity induction on stem cells from human exfoliated deciduous teeth. First, the cotton CNF was characterized. Then, the cytocompatibility and the osteogenic differentiation induced by cotton CNF were examined. The results revealed that cotton CNFs have about 6-18 nm diameters, and the zeta potential was −10 mV. Despite gene expression alteration, the cotton CNF shows good cytocompatibility. The cotton CNF induced an increase in phosphatase alkaline activity and extracellular matrix mineralization. The results indicate that cotton CNF has good cytocompatibility and can promote cell differentiation without using chemical inducers, showing great potential as a new differentiation inductor for tissue engineering and regenerative medicine applications.
Emerging evidence of antibody-independent functions, as well as the clinical efficacy of anti-CD20 depleting therapies, helped to reassess the contribution of B cells during multiple sclerosis (MS) ...pathogenesis.
To investigate whether CD19
B cells may share expression of the serine-protease granzyme-B (GzmB), resembling classical cytotoxic CD8
T lymphocytes, in the peripheral blood from relapsing-remitting MS (RRMS) patients.
In this study, 104 RRMS patients during different treatments and 58 healthy donors were included. CD8, CD19, Runx3, and GzmB expression was assessed by flow cytometry analyses.
RRMS patients during fingolimod (FTY) and natalizumab (NTZ) treatment showed increased percentage of circulating CD8
GzmB
T lymphocytes when compared to healthy volunteers. An increase in circulating CD19
GzmB
B cells was observed in RRMS patients during FTY and NTZ therapies when compared to glatiramer (GA), untreated RRMS patients, and healthy donors but not when compared to interferon-β (IFN). Moreover, regarding Runx3, the transcriptional factor classically associated with cytotoxicity in CD8
T lymphocytes, the expression of GzmB was significantly higher in CD19
Runx3
-expressing B cells when compared to CD19
Runx3
counterparts in RRMS patients.
CD19
B cells may exhibit cytotoxic behavior resembling CD8
T lymphocytes in MS patients during different treatments. In the future, monitoring "cytotoxic" subsets might become an accessible marker for investigating MS pathophysiology and even for the development of new therapeutic interventions.
Carboxylated multi-wall carbon nanotube (MWCNT-COOH) presents unique properties due to nanoscale dimensions and permits a broad range of applications in different fields, such as bone tissue ...engineering and regenerative medicine. However, the cytocompatibility of MWCNT-COOH with human stem cells is poorly understood. Thus, studies elucidating how MWCNT-COOH affects human stem cell viability are essential to a safer application of nanotechnologies. Using stem cells from the human exfoliated deciduous teeth model, we have evaluated the effects of MWCNT-COOH on cell viability, oxidative cell stress, and DNA integrity. Results demonstrated that despite the decreased metabolism of mitochondria, MWCNT-COOH had no toxicity against stem cells. Cells maintained viability after MWCNT-COOH exposure. MWCNT-COOH did not alter the superoxide dismutase activity and did not cause genotoxic effects. The present findings are relevant to the potential application of MWCNT-COOH in the tissue engineering and regenerative medicine fields.
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