Ultrasound Blood-Brain Barrier Opening and Aducanumab in Alzheimer's Disease.

Antiamyloid antibodies have been used to reduce cerebral amyloid-beta (Aß) load in patients with Alzheimer's disease. We applied focused ultrasound with each of six monthly aducanumab infusions to temporarily open the blood-brain barrier with the goal of enhancing amyloid removal in selected brain regions in three participants over a period of 6 months. The reduction in the level of Aß was numerically greater in regions treated with focused ultrasound than in the homologous regions in the contralateral hemisphere that were not treated with focused ultrasound, as measured by fluorine-18 florbetaben positron-emission tomography. Cognitive tests and safety evaluations were conducted over a period of 30 to 180 days after treatment. (Funded by the Harry T. Mangurian, Jr. Foundation and the West Virginia University Rockefeller Neuroscience Institute.).

Estimation and probabilistic projection of age- and sex-specific mortality rates across Brazilian municipalities between 2010 and 2030.

BACKGROUND: Mortality rate estimation in small areas can be difficult due the low number of events/exposure (i.e. stochastic error). If the death records are not completed, it adds a systematic uncertainty on the mortality estimates. Previous studies in Brazil have combined demographic and statistical methods to partially overcome these issues. We estimated age- and sex-specific mortality rates for all 5,565 Brazilian municipalities in 2010 and forecasted probabilistic mortality rates and life expectancy between 2010 and 2030. METHODS: We used a combination of the Tool for Projecting Age-Specific Rates Using Linear Splines (TOPALS), Bayesian Model, Spatial Smoothing Model and an ad-hoc procedure to estimate age- and sex-specific mortality rates for all Brazilian municipalities for 2010. Then we adapted the Lee-Carter model to forecast mortality rates by age and sex in all municipalities between 2010 and 2030. RESULTS: The adjusted sex- and age-specific mortality rates for all Brazilian municipalities in 2010 reveal a distinct regional pattern, showcasing a decrease in life expectancy in less socioeconomically developed municipalities when compared to estimates without adjustments. The forecasted mortality rates indicate varying regional improvements, leading to a convergence in life expectancy at birth among small areas in Brazil. Consequently, a reduction in the variability of age at death across Brazil's municipalities was observed, with a persistent sex differential. CONCLUSION: Mortality rates at a small-area level were successfully estimated and forecasted, with associated uncertainty estimates also generated for future life tables. Our approach could be applied across countries with data quality issues to improve public policy planning.

Cortical Thickness Correlates of Go/No-go and Motor Sequencing in Mild Cognitive Impairment and Suspected Alzheimer Disease Dementia.

BACKGROUND: While the cognitive hallmark of typical Alzheimer's disease (AD) is impaired memory consolidation, increasing evidence suggests that the frontal lobes and associated executive functions are also impacted. OBJECTIVE: We examined two neurobehavioral executive function tasks and associations with cortical thickness in patients diagnosed with mild cognitive impairment (MCI), suspected AD dementia, and a healthy control group. METHODS: First, we compared group performances on a go/no-go (GNG) task and on Luria's Fist-Edge-Palm (FEP) motor sequencing task. We then examined correlations between neurobehavioral task performance and the thickness of frontal cortical regions, AD signature regions, broader unbiased brain regions, and white matter hyperintensities (WMH). RESULTS: Participants with MCI performed worse than healthy controls, but better than participants with suspected AD dementia on both tasks. Both GNG and FEP (to a slightly greater extent) tasks showed diffuse associations with most AD signature regions and multiple additional regions within the temporal, parietal, and occipital cortices. Similarly, both tasks showed significant associations with all other cognitive tasks examined. Of the frontal regions examined, only the middle frontal gyrus and pars opercularis were associated with performance on these tasks. Interactions between the precuneus and transtemporal gyri were most predictive of GNG task performance, while the interaction between superior temporal and lingual gyri was most predictive of FEP task performance. CONCLUSION: This study replicates difficulties with both GNG and FEP tasks in participants with MCI and AD dementia. Both tasks showed widespread associations with the cortical thickness of various brain structures rather than localizing to frontal regions, consistent with the diffuse nature of AD.

Cesarean sections and early-term births according to Robson classification: a population-based study with more than 17 million births in Brazil.

BACKGROUND: Cesarean section (CS) rates are increasing worldwide and are associated with negative maternal and child health outcomes when performed without medical indication. However, there is still limited knowledge about the association between high CS rates and early-term births. This study explored the association between CSs and early-term births according to the Robson classification. METHODS: A population-based, cross-sectional study was performed with routine registration data of live births in Brazil between 2012 and 2019. We used the Robson classification system to compare groups with expected high and low CS rates. We used propensity scores to compare CSs to vaginal deliveries (1:1) and estimated associations with early-term births using logistic regression. RESULTS: A total of 17,081,685 live births were included. Births via CS had higher odds of early-term birth (OR 1.32; 95% CI 1.32-1.32) compared to vaginal deliveries. Births by CS to women in Group 2 (OR 1.50; 95% CI 1.49-1.51) and 4 (OR 1.57; 95% CI 1.56-1.58) showed the highest odds of early-term birth, compared to vaginal deliveries. Increased odds of an early-term birth were also observed among births by CS to women in Group 3 (OR 1.30, 95% CI 1.29-1.31), compared to vaginal deliveries. In addition, live births by CS to women with a previous CS (Group 5 - OR 1.36, 95% CI 1.35-1.37), a single breech pregnancy (Group 6 - OR 1.16; 95% CI 1.11-1.21, and Group 7 - OR 1.19; 95% CI 1.16-1.23), and multiple pregnancies (Group 8 - OR 1.46; 95% CI 1.40-1.52) had high odds of an early-term birth, compared to live births by vaginal delivery. CONCLUSIONS: CSs were associated with increased odds of early-term births. The highest odds of early-term birth were observed among those births by CS in Robson Groups 2 and 4.

Perinatal Health in Amazon Triple Border Region: Cross-Sectional Analysis Comparing Outcomes in the Brazilian, Peruvian and Colombian Population.

OBJECTIVE: To investigate the perinatal outcomes in Brazilian, Peruvian, and Colombian women in a Brazilian reference maternity hospital based at Amazon triple border region. METHOD: A cross-sectional case study of data from 3242 live birth certificates issued at the Tabatinga public maternity hospital, in the countryside of Amazonas, in the period between January 2015 and December 2017. Maternal and perinatal independent variables were analysed based on central tendency and variability, and frequency distribution for categorical variables. The Pearson's Chi-Square test and univariate analyses were performed to estimate probability ratios (Odds Ratio-OR). RESULTS: Significant differences were found in the education level in the three population groups, as well as in the number of previous pregnancies, antenatal consultations, month of initial prenatal care, and type of delivery. Brazilian pregnant women had more prenatal consultations, caesarean sections, and premature births. Peruvian and Colombian women started antenatal care later, and those with high-risk pregnancies tended to deliver in their home country. CONCLUSION FOR PRACTICE: Our findings show some singularities in the care of women and infants in the Amazonian triple border region. The Brazilian Unified Health Care System performs an important role in the guarantee of free access to health services, and ensures comprehensive care for women and infants, promoting human rights in border regions regardless of nationality.

Physical disabilities caused by leprosy in 100 million cohort in Brazil.

BACKGROUND: Leprosy continues to be an important cause of physical disability in endemic countries such as Brazil. Knowledge of determinants of these events may lead to better control measures and targeted interventions to mitigate its impact on affected individuals. This study investigated such factors among the most vulnerable portion of the Brazilian population. METHODS: A large cohort was built from secondary data originated from a national registry of applicants to social benefit programs, covering the period 2001-2015, including over 114 million individuals. Data were linked to the leprosy notification system utilizing data from 2007 until 2014. Descriptive and bivariate analyses lead to a multivariate analysis using a multinomial logistic regression model with cluster-robust standard errors. Associations were reported as Odds Ratios with their respective 95% confidence intervals. RESULTS: Among the original cohort members 21,565 new leprosy cases were identified between 2007 and 2014. Most of the cases (63.1%) had grade zero disability. Grades 1 and 2 represented 21 and 6%, respectively. Factors associated with increasing odds of grades 1 and 2 disability were age over 15 years old (ORs 2.39 and 1.95, respectively), less schooling (with a clear dose response effect) and being a multibacillary patient (ORs 3.5 and 8.22). Protective factors for both grades were being female (ORs 0.81 and 0.61) and living in a high incidence municipality (ORs 0.85 and 0.67). CONCLUSIONS: The findings suggest that the developing of physical disabilities remains a public health problem which increases the burden of leprosy, mainly for those with severe clinical features and worse socioeconomic conditions. Early diagnosis is paramount to decrease the incidence of leprosy-related disability and our study points to the need for strengthening control actions in non-endemic areas in Brazil, where cases may be missed when presented at early stages in disease. Both actions are needed, to benefit patients and to achieve the WHO goal in reducing physical disabilities among new cases of leprosy.

The ability of Lactococcus lactis subsp. lactis bv. diacetylactis strains in producing nisin.

Lactococcus lactis subsp. lactis bv. diacetylactis is a relevant microorganism for the dairy industry because of its role in the production of aromatic compounds. Despite this technological property, the identification of bacteriocinogenic potential of obtained strains can offer the additional positive aspect of biosafety. A panel of 15 L. lactis subsp. lactis bv. diacetylactis strains was characterised for the presence and expression of bacteriocin related genes, and further investigated regarding the nisin operon. Eight strains were positive only for nisA, and one strain (SBR4) presented a full nisin operon, with sequencing that was shown to be similar to nisin Z. Only SBR4 presented inhibitory activity against 16 microbial target strains. The growth curves of selected targets strains confirmed the inhibitory activity of SBR4 and consequently the nisin production. This research has demonstrated the inhibitory potential of L. lactis subsp. lactis bv. diacetylactis strain, SBR4, due to its ability to produce nisin Z. This biopreservative potential, associated to previously characterised technological properties, allow the indication of this strain as a promising candidate to be used by the dairy industry as a starter or adjunct culture.

Intranetwork and internetwork connectivity in patients with Alzheimer disease and the association with cerebrospinal fluid biomarker levels.

BACKGROUND: In the last decade, many studies have reported abnormal connectivity within the default mode network (DMN) in patients with Alzheimer disease. Few studies, however, have investigated other networks and their association with pathophysiological proteins obtained from cerebrospinal fluid (CSF). METHODS: We performed 3 T imaging in patients with mild Alzheimer disease, patients with amnestic mild cognitive impairment (aMCI) and healthy controls, and we collected CSF samples from the patients with aMCI and mild Alzheimer disease. We analyzed 57 regions from 8 networks. Additionally, we performed correlation tests to investigate possible associations between the networks' functional connectivity and the protein levels obtained from the CSF of patients with aMCI and Alzheimer disease. RESULTS: Our sample included 41 patients with Alzheimer disease, 35 with aMCI and 48 controls. We found that the main connectivity abnormalities in those with Alzheimer disease occurred between the DMN and task-positive networks: these patients presented not only a decreased anticorrelation between some regions, but also an inversion of the correlation signal (positive correlation instead of anticorrelation). Those with aMCI did not present statistically different connectivity from patients with Alzheimer disease or controls. Abnormal levels of CSF proteins were associated with functional disconnectivity between several regions in both the aMCI and mild Alzheimer disease groups, extending well beyond the DMN or temporal areas. LIMITATIONS: The presented data are cross-sectional in nature, and our findings are dependent on the choice of seed regions used. CONCLUSION: We found that the main functional connectivity abnormalities occur between the DMN and task-positive networks and that the pathological levels of CSF biomarkers correlate with functional connectivity disruption in patients with Alzheimer disease.

Benzodiazepines for restless legs syndrome.

BACKGROUND: Restless legs syndrome (RLS) is a common disease affecting about 5% to 15% of the population. Symptoms of RLS can be severe in a minority of and can have a major impact on sleep, mostly sleep initiation, and quality of life. Benzodiazepines are drugs that can induce and maintain sleep and, hence, intuitively are thought to be beneficial to people with RLS. Altough benzodiazepines, particularly clonazepam, are used to treat RLS symptoms, a systematic review done by the American Academy of Sleep Medicine stated that benzodiazepines should not be used as a first-line treatment, although could be used as a coadjuvant therapy. OBJECTIVES: To evaluate the efficacy and safety of benzodiazepine compared to placebo or other treatment for idiopathic RLS, including unconfounded trials comparing benzodiazepines versus open control. SEARCH METHODS: In March 2016 we searched CENTRAL, MEDLINE, Embase and LILACS We checked the references of each study and contacted study authors to identify any additional studies. We considered studies published in any language. SELECTION CRITERIA: Randomised clinical trials of benzodiazepine treatment in idiopathic RLS. DATA COLLECTION AND ANALYSIS: We did not perform data collection and analysis, since we did not include any studies, MAIN RESULTS: We did not identify any studies that met the inclusion criteria of the review. Two cross-over studies are awaiting classification because the cross-over trials did not give data at the end of the first cross-over period. AUTHORS' CONCLUSIONS: The effectiveness of benzodiazepines for RLS treatment is currently unknown.

Vulnerability to loss of follow-up and death due to tuberculosis among homeless individuals in Brazil: a retrospective cohort study. / Vulnerabilidade à perda de seguimento e ao óbito por tuberculose nas pessoas em situação de rua no Brasil: um estudo de coorte retrospectiva.

This retrospective cohort study identified factors associated with loss of follow-up and death due to tuberculosis (TB) in the homeless population (HP) in Brazil, estimating odds ratios (OR) and their 95% confidence intervals (95%CI) by multinomial logistic regression. A total of 3,831 TB cases in this population were analyzed, of which 57.0% had unfavorable outcomes. Loss of follow-up was associated with: history of abandonment (OR=2.38; 95%CI 2.05-2.77), unknown HIV serology (OR=1.79; 95%CI 1.38-2.32), HIV coinfection (OR=1.73; 95%CI 1.46-2.06), drug use (OR=1.54; 95%CI 1.31-1.80), age (OR=0.98; 95%CI 0.97-0.99), mixed clinical form (OR=0.64; 95%CI 0.42-0.97), extrapulmonary form (OR=0.46; 95%CI 0.29-0.73), government beneficiary (OR=0.64; 95%CI 0.50-0.81), and supervised treatment (OR=0.52; 95%CI 0.45-0.60). Regarding death, the following were associated: age (OR=1.03; 95%CI 1.01-1.05), unknown HIV serology (OR=2.39; 95%CI 1.48-3.86), alcohol consumption (OR=1.81; 95%CI 1.27-2.58), and supervised treatment (OR=0.70; 95%CI 0.51-0.96). Overlapping vulnerabilities in the health-disease process of homeless individuals with TB were observed, requiring comprehensive and cross-sectoral care practices.

Esta coorte retrospectiva identificou os fatores associados à perda de seguimento e ao óbito por tuberculose na população em situação de rua no Brasil, estimando-se as odds ratios (OR) e seus intervalos de confiança de 95% (IC95%) por regressão logística multinominal. Analisaram-se 3.831 casos de tuberculose nessa população, dos quais 57,0% tiveram desfechos desfavoráveis. Associaram-se à perda de seguimento: histórico de abandono (OR=2,38; IC95% 2,05-2,77), desconhecimento da sorologia do HIV (OR=1,79; IC95% 1,38-2,32) e coinfecção com HIV (OR=1,73; IC95% 1,46-2,06), uso de drogas (OR=1,54; IC95% 1,31-1,80), idade (OR=0,98; IC95% 0,97-0,99), forma clínica mista (OR=0,64; IC95% 0,42-0,97) e extrapulmonar (OR=0,46; IC95% 0,29-0,73), auxílio de programa governamental (OR=0,64; IC95% 0,50-0,81) e tratamento supervisionado (OR=0,52; IC95% 0,45-0,60). Em relação ao óbito, associaram-se: idade (OR=1,03; IC95% 1,01-1,05), desconhecimento da sorologia do HIV (OR=2,39; IC95% 1,48-3,86), uso de álcool (OR=1,81; IC95% 1,27-2,58) e tratamento supervisionado (OR=0,70; IC95% 0,51-0,96). Percebeu-se a sobreposição de vulnerabilidades no processo saúde-doença das pessoas em situação de rua com tuberculose, demandando práticas cuidativas intersetoriais e integrais.

Assessment of safety and in situ antibacterial activity of Weissella cibaria strains isolated from dairy farms in Minas Gerais State, Brazil, for their food application.

Weissella cibaria W21, W25, and W42 strains have previously been characterized for their antagonism against a range of foodborne pathogens. However, prior to their use as protective agents, further analyses such as their safety and in situ activity are needed. The safety of W. cibaria W21, W25, and W42 strains was predicted in silico and confirmed experimentally. Analyses of their genomes using appropriate software did not reveal any acquired antimicrobial resistance genes, nor mobile genetic elements (MGEs). The survival of each strain was determined in vitro under conditions mimicking the gastrointestinal tract (GIT). Thus, hemolysis analysis was performed using blood agar and the cytotoxicity assay was determined using a mixture of two cell lines (80% of Caco-2 and 20% of HT-29). We also performed the inflammation and anti-inflammation capabilities of these strains using the promonocytic human cell line U937. The Weissella strains were found to be haemolysis-negative and non-cytotoxic and did not induce any inflammation. Furthermore, these strains adhered tightly to intestinal Caco-2 cell-lines and exerted in situ anti-proliferative activity against methicillin-resistant Staphylococcus aureus (strain MRSA S1) and Escherichia coli 181, a colistin-resistant strain. However, the W. cibaria strains showed low survival rate under simulated GIT conditions in vitro. The unusual LAB-strains W. cibaria strains W21, W25, and W42 are safe and endowed with potent antibacterial activities. These strains are therefore good candidates for industrial applications. The results of this study provide a characterization and insights into Weissella strains, which are considered unusual LAB, but which prompt a growing interest in their bio-functional properties and their potential industrial applications.

Incidence and risk factors of tuberculosis among 420 854 household contacts of patients with tuberculosis in the 100 Million Brazilian Cohort (2004-18): a cohort study.

BACKGROUND: Although household contacts of patients with tuberculosis are known to be particularly vulnerable to tuberculosis, the published evidence focused on this group at high risk within the low-income and middle-income country context remains sparse. Using nationwide data from Brazil, we aimed to estimate the incidence and investigate the socioeconomic and clinical determinants of tuberculosis in a cohort of contacts of tuberculosis patients. METHODS: In this cohort study, we linked individual socioeconomic and demographic data from the 100 Million Brazilian Cohort to mortality data and tuberculosis registries, identified contacts of tuberculosis index patients diagnosed from Jan 1, 2004 to Dec 31, 2018, and followed up the contacts until the contact's subsequent tuberculosis diagnosis, the contact's death, or Dec 31, 2018. We investigated factors associated with active tuberculosis using multilevel Poisson regressions, allowing for municipality-level and household-level random effects. FINDINGS: We studied 420 854 household contacts of 137 131 tuberculosis index patients. During the 15 years of follow-up (median 4·4 years [IQR 1·9-7·6]), we detected 8953 contacts with tuberculosis. The tuberculosis incidence among contacts was 427·8 per 100 000 person-years at risk (95% CI 419·1-436·8), 16-times higher than the incidence in the general population (26·2 [26·1-26·3]) and the risk was prolonged. Tuberculosis incidence was associated with the index patient being preschool aged (<5 years; adjusted risk ratio 4·15 [95% CI 3·26-5·28]) or having pulmonary tuberculosis (2·84 [2·55-3·17]). INTERPRETATION: The high and sustained risk of tuberculosis among contacts reinforces the need to systematically expand and strengthen contact tracing and preventive treatment policies in Brazil in order to achieve national and international targets for tuberculosis elimination. FUNDING: Wellcome Trust and Brazilian Ministry of Health.

Geography and public health: analysis of the epidemiological dynamics of meningitis in Brazil, between 2010 and 2019.

OBJECTIVE: To analyze the spatiotemporal epidemiological dynamics of meningitis in Brazil, between 2010 and 2019. METHODS: Descriptive ecological study with cases and deaths due to meningitis in Brazil (2010-2019) in the National Notifiable Diseases Information System (Sistema de Informações de Agravos de Notificação - SINAN). The following analyses were performed: (I) frequency analyses of cases and deaths, prevalence rates, mortality, lethality, Fisher's exact test, and chi-square test; (II) Prais-Winstein regression; and (III) Global, Local Moran's index, and Kernel density. RESULTS: 182,126 cases of meningitis were reported in Brazil, of which 16,866 (9.26%) resulted in death, with prevalence rates of 9.03/100,000 inhabitants, mortality of 0.84/100,000 inhabitants, and lethality of 9.26%. There was a noted trend of decreasing prevalence rates (-9.5%, 95% confidence interval - 95%CI -13.92; -4.96, p<0.01) and mortality (-11.74%, 95%CI -13.92; -9.48, p<0.01), while lethality remained stable (-2.08%, 95%CI -4.9; 0.8; p<0.1941). The majority of cases were viral meningitis (45.7%), among 1-9 years old (32.2%), while the highest proportion of deaths was due to bacterial meningitis (68%), among 40-59 years old (26.3%). In the Moran and Kernel maps of prevalence and mortality rates, municipalities in the South, Southeast, and the capital of Pernambuco in the Northeast stood out with high rates; as for lethality, the North, Northeast, and Southeast coastal areas were highlighted. CONCLUSION: A decrease in meningitis cases and deaths was found in this study; however, the lethality rate was higher in areas with lower prevalence, emphasizing the need to enhance actions for identifying, monitoring, and providing health care for cases, as well as expanding vaccination coverage.

Novel Class of Crystal/Glass Ultrafine Nanolaminates with Large and Tunable Mechanical Properties.

The control of local heterogeneities in metallic glasses (MGs) represents an emerging field to improve their plasticity, preventing the propagation of catastrophic shear bands (SBs) responsible for the macroscopically brittle failure. To date, a nanoengineered approach aimed at finely tuning local heterogeneities controlling SB nucleation and propagation is still missing, hindering the potential to develop MGs with large and tunable strength/ductility balance and controlled deformation behavior. In this work, we exploited the potential of pulsed laser deposition (PLD) to synthesize a novel class of crystal/glass ultrafine nanolaminates (U-NLs) in which a ∼4 nm thick crystalline Al separates 6 and 9 nm thick Zr50Cu50 glass nanolayers, while reporting a high density of sharp interfaces and large chemical intermixing. In addition, we tune the morphology by synthesizing compact and nanogranular U-NLs, exploiting, respectively, atom-by-atom or cluster-assembled growth regimes. For compact U-NLs, we report high mass density (∼8.35 g/cm3) and enhanced and tunable mechanical behavior, reaching maximum values of hardness and yield strength of up to 9.3 and 3.6 GPa, respectively. In addition, we show up to 3.6% homogeneous elastoplastic deformation in compression as a result of SB blocking by the Al-rich sublayers. On the other hand, nanogranular U-NLs exhibit slightly lower yield strength (3.4 GPa) in combination with enhanced elastoplastic deformation (∼6%) followed by the formation of superficial SBs, which are not percolative even at deformations exceeding 15%, as a result of the larger free volume content within the cluster-assembled structure and the presence of crystal/glass nanointerfaces, enabling to accommodate SB events. Overall, we show how PLD enables the synthesis of crystal/glass U-NLs with ultimate control of local heterogeneities down to the atomic scale, providing new nanoengineered strategies capable of deep control of the deformation behavior, surpassing traditional trade-off between strength and ductility. Our approach can be extended to other combinations of metallic materials with clear interest for industrial applications such as structural coatings and microelectronics (MEMS and NEMS).

More Similar than Different: Memory, Executive Functions, Cortical Thickness, and Glucose Metabolism in Biomarker-Positive Alzheimer's Disease and Behavioral Variant Frontotemporal Dementia.

Background: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are typically associated with very different clinical and neuroanatomical presentations; however, there is increasing recognition of similarities. Objective: To examine memory and executive functions, as well as cortical thickness, and glucose metabolism in AD and bvFTD signature brain regions. Methods: We compared differences in a group of biomarker-defined participants with Alzheimer's disease and a group of clinically diagnosed participants with bvFTD. These groups were also contrasted with healthy controls (HC). Results: As expected, memory functions were generally more impaired in AD, followed by bvFTD, and both clinical groups performed more poorly than the HC group. Executive function measures were similar in AD compared to bvFTD for motor sequencing and go/no-go, but bvFTD had more difficulty with a set shifting task. Participants with AD showed thinner cortex and lower glucose metabolism in the angular gyrus compared to bvFTD. Participants with bvFTD had thinner cortex in the insula and temporal pole relative to AD and healthy controls, but otherwise the two clinical groups were similar for other frontal and temporal signature regions. Conclusions: Overall, the results of this study highlight more similarities than differences between AD and bvFTD in terms of cognitive functions, cortical thickness, and glucose metabolism. Further research is needed to better understand the mechanisms mediating this overlap and how these relationships evolve longitudinally.

Evaluation of low-level laser therapy in patients with acute and chronic temporomandibular disorders.

The purpose of this study was to address the following question: among patients with acute or chronic temporomandibular disorders (TMD), does low-level laser therapy (LLLT) reduce pain intensity and improve maximal mouth opening? The sample comprised myogenic TMD patients (according Research Diagnostic Criteria for TMD). Inclusion criteria were: male/female, no age limit, orofacial pain, tender points, limited jaw movements and chewing difficulties. Patients with other TMD subtypes or associated musculoskeletal/rheumatologic disease, missing incisors teeth, LLLT contra-indication, and previous TMD treatment were excluded. According to disease duration, patients were allocated into two groups, acute (<6 months) and chronic TMD (≥ 6 months). For each patient, 12 LLLT sessions were performed (gallium-aluminum-arsenide; λ = 830 nm, P = 40 mW, CW, ED = 8 J/cm(2)). Pain intensity was recorded using a 10-cm visual analog scale and maximal mouth opening using a digital ruler (both recorded before/after LLLT). The investigators were previously calibrated and blinded to the groups (double-blind study) and level of significance was 5% (p < 0.05). Fifty-eight patients met all criteria, 32 (acute TMD), and 26 (chronic TMD). Both groups had a significant pain intensity reduction and maximal mouth opening improvement after LLLT (Wilcoxon test, p < 0.001). Between the groups, acute TMD patient had a more significant pain intensity reduction (Mann-Whitney test, p = 0.002) and a more significant maximal mouth opening improvement (Mann-Whitney test, p = 0.011). Low-level laser therapy can be considered as an alternative physical modality or supplementary approach for management of acute and chronic myogenic temporomandibular disorder; however, patients with acute disease are likely to have a better outcome.

Effects of square-stepping exercise on cognitive functions of older people.

AIM: Cognitive functions can decline with age, and interventions focusing on stimulating them may have positive results. Previous studies have shown that square-stepping exercise (SSE) has a good influence on balance, but this exercise also seems to promote cognitive stimulation. Therefore, the purpose of the present study was to analyse the effect of 16 weeks of SSE on cognitive functions in non-demented community-dwelling older people. METHODS: This was a longitudinal, non-randomized study. Forty-one older adults (60 years and older) were recruited, and 21 participated in the SSE group (practised only SSE sequences) and 20 were in the control group (continued with their activities of daily living). Both groups were evaluated using the Mini-Mental State Examination, the Digit Span test, the Toulouse-Pierón Attention Test and the Modified Card Sorting Test. RESULTS: The SSE group showed a significant improvement in global cognitive status, concentrated attention and mental flexibility after 16 weeks of the SSE intervention. CONCLUSION: Evidence shows that SSE is a physical activity that positively influences cognitive functions in non-demented older people.

Effect of agility ladder training with a cognitive task (dual task) on physical and cognitive functions: a randomized study.

Introduction: Agility training (AT) is used to improve neuromuscular performance and dynamic balance, which are crucial for the physical function of older adults. Activities of daily living, which decrease with age, involve tasks that simultaneously require motor, and cognitive abilities and can be considered dual tasks. Methods: This study investigates a training program's physical and cognitive effects using an agility ladder on healthy older adults. This program consisted of 30-min sessions twice per week and lasted for 14 weeks. The physical training included four different sequences with progressive difficulty levels, while the cognitive training (CT) included different verbal fluency (VF) tasks for each physical task. Sixteen participants (mean age of 66.9 ± 5.0 years) were allocated to two groups: AT alone (AT) and dual-task training (AT combined with CT [AT + CT]). Assessments were performed before and after 14 weeks of interventions using physical functional tests (e.g., Illinois agility test, five times sit-to-stand test, timed up and go [TUG], and one-leg stand) and cognitive tests (cognitive TUG, verbal fluency, attention, and scenery picture memory test). Results: After this period, both groups had significant differences in physical performance, muscle power, agility, static and dynamic balance, and short-term memory, whereas only the AT + CT group improved phonological verbal fluency, executive function (TUG combined with a cognitive task), attention (trail-making test-B), and short-term memory (scenery picture memory test). Conclusion: Indicating that only the group that received direct cognitive training had better enhanced cognitive function. Clinical trial registration: www.ClinicalTrials.gov, identifier: RBR-7t7gnjk.

Evaluation of phenotypic detection of carbapenemase-producing Pseudomonas spp. from clinical isolates.

Carbapenems are considered last-resort antibiotics for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. Although the main mechanism of carbapenem-resistance in Pseudomonas aeruginosa is the loss of OprD porin, carbapenemases continue to be a problem worldwide. The aim of this study was to evaluate the performance of phenotypic tests (Carba NP, Blue Carba, and mCIM/eCIM) for detection of carbapenemase-producing Pseudomonas spp. in Brazil. One hundred twenty-seven Pseudomonas spp. clinical isolates from different Brazilian states were submitted to phenotypic and molecular carbapenemase detection. A total of 90 carbapenemase-producing P. aeruginosa and 5 Pseudomonas putida (35, blaVIM-2; 17, blaSPM-1; 2, blaIMP-10; 1, blaVIM-24; 1, blaNDM-1; 39, blaKPC-2). The phenotypic Carba NP, Blue Carba, and mCIM/eCIM showed sensitivity of 94.7%, 93.6%, and 93.6%, and specificity of 90.6%, 100%, and 96.8%, respectively. However, only the Carba NP presented the highest sensitivity and showed the ability in differentiating the carbapenemases between class A and class B using EDTA. Blue Carba failed to detect most of the class B carbapenemases, having the worst performance using EDTA. Our results show changes in the epidemiology of the spread of carbapenemases and the importance of their detection by phenotypic and genotypic tests. Such, it is essential to use analytical tools that faithfully detect bacterial resistance in vitro in a simple, sensitive, rapid, and cost-effective way. Much effort must be done to improve the current tests and for the development of new ones.