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Lactic acid bacteria (LABs) are microorganisms of significant scientific and industrial importance and have great potential for application in meat and meat products. This comprehensive review addresses the main characteristics of LABs, their nutritional, functional, and technological benefits, and especially their importance not only as starter cultures. LABs produce several metabolites during their fermentation process, which include bioactive compounds, such as peptides with antimicrobial, antidiabetic, antihypertensive, and immunomodulatory properties. These metabolites present several benefits as health promoters but are also important from a technological point of view. For example, bacteriocins, organic acids, and other compounds are of great importance, whether from a sensory or product quality or a safety point of view. With the production of GABA, exopolysaccharides, antioxidants, and vitamins are beneficial metabolites that influence safety, technological processes, and even health-promoting consumer benefits. Despite the benefits, this review also highlights that some LABs may present virulence properties, requiring critical evaluation for using specific strains in food formulations. Overall, this review hopes to contribute to the scientific literature by increasing knowledge of the various benefits of LABs in meat and meat products.

The pathogenic nature of infections caused by Candida spp. underscores the necessity for novel therapeutic agents. Extracts of Schinopsis brasilienses Engl are \ a promising source of agents with antifungal effects. This study aimed to assess the antifungal potential of the leaf extract of S. brasilienses. The antifungal activity was evaluated by determining the minimum inhibitory concentrations and fungicide concentrations (MIC and MFC). The antibiofilm potential was assessed by counting colony-forming units/mL. The study examined the inhibition kinetics of fungal growth and potential synergism between gallic acid or the extract and nystatin using the Checkerboard method. Cytotoxicity was evaluated through the MTT assay. The extract exhibited antifungal effect against all tested strains, with MIC and MFC ranging from 31.25-250 μg/mL. Gallic acid, the main isolated compound, displayed a MIC of 2000 μg/mL. The extract of S. brasilienses at 31.25 μg/mL inhibited the formation of biofilm by C. albicans and significantly reduced the mass of mature biofilm after 24 and 48 h (p < 0. 05). At a concentration of 125 μg/mL, the extract demonstrated significant inhibition of fungal growth after 6 hours. The combination of gallic acid or extract with nystatin did not exhibit synergistic or antagonistic effect. Furthermore, the extract did not induce cytotoxicity to a human cell line. The extract of S. brasiliensis demonstrates antifungal activity against Candida, generally exhibiting fungicidal action and capacity to inhibit biofilm formation as well as reduce mature biofilms. Additionally, the extract showed low cytotoxicity to human cells.

To investigate the effectiveness of paced breathing guided by biofeedback on clinical and functional outcomes of patients with chronic obstructive pulmonary disease (COPD). An uncontrolled pilot study comprising a training with paced breathing guided by biofeedback (three sessions of 35 min per week) was conducted over four weeks (12 sessions). Assessments included respiratory muscle strength (using a manovacuometer), anxiety (Beck Anxiety Inventory), depression (Beck Depression Inventory), dyspnea (Baseline Dyspnea Index), functionality (Timed Up and Go Test), health status (COPD Assessment Test) and health-related quality of life (Saint George's Respiratory Questionnaire). The sample consisted of nine patients with a mean age of 68.2 ± 7.8 years. After intervention, patients significantly improved in health status and health-related quality of life, assessed using the COPD Assessment Test (p < 0.001) and Saint George's Respiratory Questionnaire (p < 0.001); anxiety (p < 0.001); and depression (p = 0.001). Patients also significantly improved in dyspnea (p = 0.008), TUG (p = 0.015), CC Score (p = 0.031), and maximum inspiratory (p = 0.004) and expiratory pressures (p < 0.001). An intervention with paced breathing guided by biofeedback promoted positive results on dyspnea, anxiety, depression, health status and perceived health-related quality of life in patients with COPD. Moreover, gains in respiratory muscle strength and functional performance were observed, affecting the performance of daily activities., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Rootstocks less vigorous are among the most crucial management techniques to modernize fruit cultivation. Replanting with fallow land has become necessary due to a lack of land to establish new orchards., Objective: The aim of this study is to determine the effect of various rootstocks of the American Geneva® series on the yield performance of the apple ( Malus domestica Borkh) cultivars 'Gala Select' and 'Fuji Suprema' under replanting conditions in southern Brazil. Methods : After two years of fallow land, the experiments were initiated in 2017 and conducted during the 2018, 2019, 2020, and 2021 growing seasons in Painel and Caxias do Sul municipalities at the Santa Catarina and the Rio Grande do Sul State, respectively. The 'Gala Select' and 'Fuji Suprema' were grafted onto the G.202, G.814, G.210, and G.213 Geneva series rootstocks in a tall spindle training system using a randomized complete block design with four replicates. Principal component analysis (PCA) was used to assess the interrelationship among the variable's vigor, productivity, and fruit quality., Results: The PCA result showed significant differences in vigor, productivity, and fruit quality when the G.210 and G.213 and G.814 and G.213 Geneva series rootstocks were used in combination with Gala Select and Fuji Suprema cultivars, respectively. The PCA analysis clustered all cultivar/rootstock combinations into two groups, based on their vigor and productivity and the yield performance and fruit quality data, that differed significantly among combinations and regions. The 'Gala Select'/G.202 and 'Fuji Suprema'/G.213 combinations were less vigorous than the 'Gala Select'/G.210 and 'Fuji Suprema'/G.814 combinations. However, 'Gala Select'/G.210 (semi-dwarfing) and G.213 (dwarfing) are the combinations with high yield performance, productive efficiency and fruit quality, being more reliable to the producer, and less vigorous, resulting in lower labor costs under replating conditions, with two years of fallow land, from 2018 until 2021 growing seasons., Competing Interests: On behalf of all Co-authors and been the Corresponding Author, I declare must disclose any financial and personal relationships with other people or organizations that could inappropriately influence (bias) their work., (© 2023 The Authors.)

Objective: To analyze respiratory muscle strength of patients with heart failure (HF) and correlate with functional capacity., Methods: This cross-sectional study involved patients with compensated HF of both sexes, aged above 18 years. Respiratory muscle strength was assessed by measuring maximum inspiratory (MIP) and expiratory pressures (MEP) using a manovacuometer. Patients were randomized into two groups to assess functional capacity: six-minute walk test (6MWT) and incremental shuttle walk test (ISWT)., Results: Forty-eight patients were evaluated (23 from 6MWT and 25 from ISWT group). Most were male (67.8%), with mean age of 62.3 years and left ventricular ejection fraction of 40.8%. Mean predicted values of MIP [81.2% (74.7-87.8%)] and MEP [95.6% (88.2-103.0%)] did not indicate respiratory muscle weakness. The higher the New York Heart Association (NYHA) functional class, the lower the MIP (p = .011) and MEP (p = .016) values. Physically active patients presented higher respiratory muscle strength than those sedentary (MIP: 104.5 vs. 71.9 cmH 2 O, p < .001; MEP: 120.0 vs. 91.1 cmH 2 O, p = .004). Functional capacity was impaired [6MWT: 416.0 m (372.8-459.3 m); ISWT: 304 m (263.4-344.9 m)], and distance covered in the ISWT was shorter than 6MWT group (p < .001). Distance covered in the ISWT group presented a moderate positive correlation with MIP (r = 0.45; p = .022) and MEP (r = 0.41; p = .041)., Conclusion: Most patients with HF presented respiratory muscle strength close to predicted values; however, sedentary patients and those with high NYHA functional class, showed reduced MIP and MEP. Functional capacity was reduced, and MIP and MEP correlated with distance covered in the ISWT.

Background: Biomarkers can help understand the impact of achieving therapeutic goals in developing vascular diseases in diabetics. Aim: To assess the association between lipid and glycemic profiles and endothelial biomarkers in diabetics. Methods: Cross-sectional study that evaluated lipid and glycemic levels and biomarkers (VCAM-1, Sdc-1, FGF-23 and KIM-1 in diabetics. Results: Higher VCAM-1 levels were associated with higher low-density lipoprotein cholesterol and non-high-density lipoprotein (HDL) cholesterol levels (in the group with inadequate glycohemoglobin A1c [HbA1c] levels), with higher glycemic levels (in the group with inadequate HDL cholesterol levels) and with lower HDL cholesterol levels (both groups). VCAM-1 was independently associated with not achieving adequate HbA1c levels. Conclusion: In uncontrolled diabetics, VCAM-1 was independently associated with having inadequate HbA1c levels, suggesting they may already have endothelial damage.

The aim of this study is to demonstrate the stability-indicating capacity of an analytical method for Eugenia uniflora, enhance understanding of the stability of myricitrin, and assess the effect of degradation of spray-dried extract (SDE) on antioxidant and antifungal activities. Validation of the stability-indicating method was carried out through a forced degradation study of SDE and standard myricitrin. The antioxidant and antifungal activities of SDE were evaluated both before and after degradation. The quantification method described was found to be both accurate and precise in measuring myricitrin levels in SDE from E. uniflora, with excellent selectivity that confirmed its stability-indicating capability. The forced degradation study revealed that the marker myricitrin is sensitive to hydrolysis, but generally stable under other stress conditions. By contrast, the standard myricitrin displayed greater susceptibility to degradation under forced degradation conditions. Analysis of the antioxidant activity of SDE before and after degradation showed a negative impact in this activity due to degradation, while no significant effect was observed on antifungal activity. The method described can be a valuable tool in the quality control of E. uniflora, and the findings can assist in determining the optimal conditions and storage of products derived from this species., (© 2023 John Wiley & Sons Ltd.)

The aim of the present study was to report on the occurrence of parasitism by Amblyomma rotundatum ticks on two species of Teiidae lizards and test the presence of rickettsiae in the collected ticks, in the western Brazilian Amazon region. Ticks were collected in July 2019, from a fragment of terra firme forest in the municipality of Senador Guiomard, Acre, Brazil. Two lizards that were infested by immature stages of ticks were caught using mist net and Tomahawk traps. Ectoparasites were collected manually, and the lizard specimens were identified and released at the same location where they had been caught. Three nymphs and 49 larvae were collected from Ameiva ameiva, while 25 nymphs and nine larvae were collected from Tupinambis cuzcoensis, which are both in the family Teiidae. The ticks were identified morphologically as belonging to the genus Amblyomma. Nymphs were identified at species level through molecular analysis, resulting in the tick species Amblyomma rotundatum. This is the first record of parasitism by the tick A. rotundatum on T. cuzcoensis lizard, and the first report of an association between A. rotundatum and the lizard species A. ameiva and T. cuzcoensis in Acre, in the western part of the Amazon region.

The gaining popularity of tobacco and nicotine delivery products, such as electronic cigarettes (e-cigarettes) being perceived as relatively safe is of a medical concern. The long-term safety of these new products remains uncertain for oral health. In this study, in vitro effects of e-liquid were assessed in a panel of normal oral epithelium cell lines (NOE and HMK), oral squamous cell carcinoma (OSCC) human cell lines (CAL27 and HSC3), and a mouse oral cancer cell line (AT84) using cell proliferation, survival/cell death, and cell invasion assays. In addition, signaling pathways underlying the pro-invasive activity of e-cigarettes were evaluated by gene and protein expression analysis. We demonstrated that e-liquid promotes proliferation and anchorage-independent growth of OSCC and induces morphological changes associated with enhanced motility and invasive phenotypes. Furthermore, e-liquid-exposed cells express significantly reduced cell viability, regardless of e-cigarette flavour content. At the gene expression level, e-liquid induces changes in gene expression consistent with epithelial to mesenchymal transition (EMT) revealed by reduced expression of cell epithelial markers such as E-cadherin and enhanced expression of mesenchymal proteins like vimentin and B-catenin seen both in OSCC cell lines and normal oral epithelium cells. In summary, the ability of e-liquid to induce proliferative and invasive properties along the activation of the EMT process can contribute to the development of tumorigenesis in normal epithelial cells and promote aggressive phenotype in pre-existing oral malignant cells., (© 2023. The Author(s).)

Statement of Problem: Stone casts are subject to contamination, but whether disinfectants incorporated into the stone are effective is unclear., Purpose: The purpose of this in vitro study was to evaluate the antimicrobial activity and the mechanical and surface properties of self-disinfecting gypsum (SDG) and gypsum mixed with 2% chlorhexidine (GCHX)., Material and Methods: Antimicrobial action was evaluated using the diffusion-disk technique on Streptococcus aureus and Candida albicans 1 hour and 24 hours after pouring the gypsum. The groups were SDG, GCHX, a positive control (PC) of gypsum mixed with distilled water, and a negative control (NC) of filter paper disk soaked with 2% chlorhexidine; n=8. Inhibition halos were measured using the ImageJ software program and statistically analyzed using the repeated measures mixed ANOVA with time×group interaction. Compressive strength (CS) in MPa and surface roughness (SR) in μm (parameters: Ra - roughness average; and Sa - 3-dimensional (3D) arithmetic mean of the surface profile) tests were performed to characterize the specimens (evaluated groups: SDG, GCHX, and PC; n=10). CS data were analyzed by a 2-way ANOVA with time×group interaction, and SR data by a 1-way ANOVA (α=.05)., Results: For S aureus, there were differences between GCHX and SDG at 1 hour and 24 hours (P<.05), but no significant differences were found for C albicans (P>.05). GCHX was better than PC, except for C albicans, and showed a reduction in CS when compared with PC and SDG (P<.05) at all time intervals. The SR of GCHX increased (Ra:1.76, Sa:2.08) when compared with PC (Ra:0.89, Sa:1.12) and SDG (Ra:1.03, Sa:1.35) (Ra: P<.004 and Sa: P<.001)., Conclusions: The antimicrobial activity of GCHX against S aureus was better than that of SDG, but neither had an effect against C albicans. As for CS and SR, GCHX presented a decrease in properties when compared with PC and SDG but was within the American Dental Association #25 specification values., (Copyright © 2022 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Papillary thyroid carcinoma (PTC) is the most common malignancy of the thyroid gland and early stages are curable. However, a subset of PTCs shows an unusually aggressive phenotype with extensive lymph node metastasis and higher incidence of locoregional recurrence. In this study, we investigated a large cohort of PTC cases with an unusual aggressive phenotype using a high-throughput RNA sequencing (RNA-Seq) to identify differentially regulated genes associated with metastatic PTC. All metastatic PTC with mutated BRAF (V600E) but not BRAF wild-type expressed an up-regulation of R-Spondin Protein 4 (RSPO4) concomitant with an upregulation of genes involved in focal adhesion and cell-extracellular matrix signaling. Further immunohistochemistry validation confirmed the upregulation of these target genes in metastatic PTC cases. Preclinical studies using established PTC cell lines support that RSPO4 overexpression is associated with BRAF V600E mutation and is a critical upstream event that promote activation of kinases of focal adhesion signaling known to drive cancer cell locomotion and invasion. This finding opens up the potential of co-targeting B-Raf, RSPO and focal adhesion proteins as a pharmacological approach for aggressive BRAF V600E PTC.

Objective: Currently, not much is known about the interactions between voice and growth hormone (GH). We have described large kindred with isolated GH deficiency (IGHD) due to a GHRH receptor mutation, resulting in severe short stature and high-pitched voice. These IGHD individuals have little interest in GH treatment, as they consider themselves "short long-lived people", rather than patients. Interestingly, they report normal general quality of life, but they rate their Voice-Related Quality of Life (V-RQOL) as low. Here, we assessed the social and auditory-perceptual impacts of artistic-intervention voice therapy with semioccluded vocal tract exercises (SOVTE) and choral singing, on their voices., Methods: Seventeen GH-naïve adult IGHD individuals were enrolled in a single-arm interventional pre-post study with 13 weekly sessions of choir singing over 90 days. Outcome measures were V-RQOL scores, self-assessment of voice, and auditory-perceptual analysis (GRBAS scale, G: grade of the severity of dysphonia; R: roughness; B: breathiness; A: asthenia; and S: strain)., Results: Marked improvements in total (p = 0.0001), physical (p = 0.0002), and socioemotional (p = 0.0001) V-RQOL scores and in self-assessment of voice (p = 0.004) were found. The general grades of vocal deviation (p = 0.0001), roughness (p = 0.0001), breathiness (p = 0.0001) and strain (p = 0.0001) exhibited accentuated reductions., Conclusion: Voice therapy with semioccluded vocal tract exercises and choral training improved social impact and perceptual voice assessments in IGHD subjects and markedly improved their voice-related quality of life. This is particularly important in a setting where GH replacement therapy is not widely accepted.

Coffee ( Coffea arabica L.) presents an asynchronous flowering regulated by an endogenous and environmental stimulus, and anthesis occurs once plants are rehydrated after a period of water deficit. We evaluated the evolution of Abscisic Acid (ABA), ethylene, 1-aminocyclopropane-1-carboxylate (ACC) content, ACC oxidase (ACO) activity, and expression analysis of the Lysine Histidine Transporter 1 ( LHT1 ) transporter, in the roots, leaves, and flower buds from three coffee genotypes ( C. arabica L. cv Oeiras, Acauã, and Semperflorens) cultivated under field conditions with two experiments. In a third field experiment, the effect of the exogenous supply of ACC in coffee anthesis was evaluated. We found an increased ACC level, low ACO activity, decreased level of ethylene, and a decreased level of ABA in all tissues from the three coffee genotypes in the re-watering period just before anthesis, and a high expression of the LHT1 in flower buds and leaves. The ethylene content and ACO activity decreased from rainy to dry period whereas the ABA content increased. A higher number of opened and G6 stage flower buds were observed in the treatment with exogenous ACC. The results showed that the interaction of ABA-ACO-ethylene and intercellular ACC transport among the leaves, buds, and roots in coffee favors an increased level of ACC that is most likely, involved as a modulator in coffee anthesis. This study provides evidence that ACC can play an important role independently of ethylene in the anthesis process in a perennial crop., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 López, Silva Santos, Marquez Gutiérrez, Jaramillo Mesa, Cardon, Espíndola Lima, Almeida Lima and Chalfun-Junior.)

The continuous interest in discovering new bioactive molecules derived from natural products (NP) has stimulated the development of improved screening assays to help overcome challenges in NP-based drug discovery. Here, we describe a unique platform for the online screening of acetylcholinesterase inhibitors without the need for pre-treating the sample. In the current study, we have demonstrated the ability to combine reversed-phase separation with a capillary immobilized enzyme reactor (cIMER) in two-dimensional liquid chromatography system coupled with mass spectrometry detection. We systematically investigated the effects of method parameters that are of practical significance and are known to affect the enzyme assay and interfere in the analysis such as: bioreactor dimensions, loop sizes, amount of immobilized enzyme, second dimension flow rates, reaction time, substrate concentration, presence of organic modifier, limit of detection and signal suppression. The performance of this new platform was evaluated using a mixture containing three known AChE inhibitors (tacrine, galanthamine and donepezil) and an ethanolic extract obtained from the dry bulbs of Hippeastrum calyptratum (Amaryllidaceae) was investigated to provide a proof of concept of the applicability of the platform for the analysis of complex mixtures such as those derived from NPs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Seidl, Lima, Leme, Pires, Stoll and Cardoso.)

Background: Hemispherectomy has an established role as a treatment of last resort in patients with unilateral hemispheric lesions suffering from refractory epilepsy., Methods: Seven patients were evaluated at our Epilepsy Unit. We compared the seizure outcome at 6 months, 1, 2, 5 years post-surgery, as well as at end follow-up (mean 7.1 years) using Engel classification. Reduction of antiepileptic drugs (AEDs) was also assessed utilizing equal time frames., Results: The mean age of seizure onset was 5.4 years. Engel I was achieved in 5 patients at 6 months (71.4%). Engel at 1 year was predicted by the Engel at 6 months (p=0.013) with a similar number of patients being classified as Engel I outcome. Engel at 2 years was also predicted by Engel at 6 months and at 1 year (p=0.030). At end follow-up only 3 patients (42.9%) remained categorized as Engel I outcome. There was a trend toward a stability in Engel classification. All patients with developmental causes for their epilepsy experienced some deterioration of the surgical outcomes. Conversely, all patients with acquired causes were stable throughout follow-up. Seizure outcome at 6 months was worse in the patients who had post-op complications (p=0.044). Adult and pediatric populations did not differ significantly in any tested variable., Conclusions: Hemispherectomy is a valuable resource for seizure control in properly selected patients. Engel patient's evolution could be predicted at 6 months interval. Hemispherectomy could be considered a useful attitude in difficult cases., (Copyright © 2021 Sociedad Española de Neurocirugía. Published by Elsevier España, S.L.U. All rights reserved.)

The commercial determinants of health (CDoH) describe the adverse health effects associated with for-profit actors and their actions. Despite efforts to advance the definition, conceptualization, and empirical analyses of CDoH, the term's practical application to mitigate these effects requires the capacity to measure the influences of specific components of CDoH and the cumulative impacts of CDoH on the health and well-being of specific populations. Building on the Global Burden of Disease Study, we begin by conceptualizing CDoH as risk factor exposures that span agency and structural influences. We identify 6 components of these influences and propose an initial set of indicators and datasets to rank exposures as high, medium, or low. These are combined into a commercial determinants of health index (CDoHi) and illustrated by 3 countries. Although now a proof of concept, comparative analysis of CDoH exposures by population, over time and space, and their associated health outcomes will become possible with further development of indicators and datasets. Expansion of the CDoHi and application to varied populations groups will enable finer targeting of interventions to reduce health harms. The measurement of improvements to health and wellness from such interventions will, in turn, inform overall efforts to address the CDoH.

In recent years, the concept of commercial determinants of health (CDoH) has attracted scholarly, public policy, and activist interest. To date, however, this new attention has failed to yield a clear and consistent definition, well-defined metrics for quantifying its impact, or coherent directions for research and intervention. By tracing the origins of this concept over 2 centuries of interactions between market forces and public health action and research, we propose an expanded framework and definition of CDoH. This conceptualization enables public health professionals and researchers to more fully realize the potential of the CDoH concept to yield insights that can be used to improve global and national health and reduce the stark health inequities within and between nations. It also widens the utility of CDoH from its main current use to study noncommunicable diseases to other health conditions such as infectious diseases, mental health conditions, injuries, and exposure to environmental threats. We suggest specific actions that public health professionals can take to transform the burgeoning interest in CDoH into meaningful improvements in health. ( Am J Public Health . 2021;111(12):2202-2211. https://doi.org/10.2105/AJPH.2021.306491).

Black, Asian and Minority Ethnic (BAME) populations are at an increased risk of developing COVID-19 and consequentially more severe outcomes compared to White populations. The aim of this study was to quantify how much of the disproportionate disease burden can be attributed to ethnicity and deprivation as well as its interaction. An ecological study was conducted using data derived from the Office for National Statistics data at a Local Authority District (LAD) level in England between 1st March and 17th April 2020. The primary analysis examined how age adjusted COVID-19 mortality depends on ethnicity, deprivation, and the interaction between the two using linear regression. The secondary analysis using spatial regression methods allowed for the quantification of the extent of LAD spillover effect of COVID-19 mortality. We find that in LADs with the highest deprivation quartile, where there is a 1 percentage point increase in "Black-African (regression coefficient 2.86; 95% CI 1.08-4.64)", "Black-Caribbean (9.66: 95% CI 5.25-14.06)" and "Bangladeshi (1.95: 95% CI 1.14-2.76)" communities, there is a significantly higher age-adjusted COVID-19 mortality compared to respective control populations. In addition, the spatial regression results indicated positive significant correlation between the age-adjusted mortality in one LAD and the age-adjusted mortality in a neighbouring LAD, suggesting a spillover effect. Our results suggest targeted public health measures to support those who are deprived and belong to BAME communities as well as to encourage restricted movement between different localities to limit disease propagation.

Objective: Propose a standard, fast and accurate protocol for the processing of the temporomandibular joint (TMJ) of adults' rats for histology and immunohistochemistry reactions., Design: Wistar male rats were perfused with paraformaldehyde (4 %). The heads were fixed in formaldehyde 10 % solution for 48 h. After that, the heads were sectioned in a sagittal plane and fixed for plus 48 h. Decalcification was performed using 20 % formic acid for 96 h and delimitation of TMJ area was done. Detailed methodology to a standard extraction and processing of TMJ to histological sections is described. Different buffers, equipment, temperature and time were tested to optimize immunostaining. Morphological preservation and antigenicity were evaluated by hematoxylin and eosin staining and immunohistochemistry reaction., Results: The current findings demonstrated that TMJ fixed in 10 % formaldehyde and decalcified in 20 % formic acid optimized decalcification processing time with preservation of cell morphology. Antigen retrieval with citrate buffer in pressure cooker (2 min at 100 °C and 5 min at room temperature) demonstrated the best protocol to preservation of the structures of TMJ., Conclusions: This work demonstrates in detail a methodology of a fast and accurate TMJ processing for histology and immunohistochemistry reactions that guarantee tissue integrity and quality of staining., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Soft sensors based on deep learning have been growing in industrial process applications, inferring hard-to-measure but crucial quality-related variables. However, applications may present strong non-linearity, dynamicity, and a lack of labeled data. To deal with the above-cited problems, the extraction of relevant features is becoming a field of interest in soft-sensing. A novel deep representative learning soft-sensor modeling approach is proposed based on stacked autoencoder (SAE), mutual information (MI), and long-short term memory (LSTM). SAE is trained layer by layer with MI evaluation performed between extracted features and targeted output to evaluate the relevance of learned representation in each layer. This approach highlights relevant information and eliminates irrelevant information from the current layer. Thus, deep output-related representative features are retrieved. In the supervised fine-tuning stage, an LSTM is coupled to the tail of the SAE to address system inherent dynamic behavior. Also, a k-fold cross-validation ensemble strategy is applied to enhance the soft-sensor reliability. Two real-world industrial non-linear processes are employed to evaluate the proposed method performance. The obtained results show improved prediction performance in comparison to other traditional and state-of-art methods. Compared to the other methods, the proposed model can generate more than 38.6% and 39.4% improvement of RMSE for the two analyzed industrial cases.

The objective of this experiment was to evaluate the effect of two different pasture-based finishing strategies and lairage time on steers welfare in Uruguayan conditions. Sixty Hereford (H) and Braford (B) steers were assigned to two different diets for finishing purposes: (D1) native pasture plus corn grain (1% of live weight) (H n = 15, B n = 15) and (D2) high-quality pasture (H n = 15, B n = 15). The average daily gain was registered every 14 days, and temperaments were individually assessed one week before slaughter by three individual tests: crush score, flight time and exit speed, building a multicriterial temperament index (TIndex). Animals were slaughtered the same day in two groups (50% from D1 and 50% from D2 in each group) after traveling for 3.5 h and staying 15 (long lairage) and 3 h (short lairage) in the lairage pens, respectively. The behaviors were observed during lairage, and physiological indicators were used to assess stress at the farm after transport, after lairage and at slaughter. Bruises incidence and final pH were registered at the abattoir as a means of assessing the overall animal welfare. Calmer animals had higher average daily gains with no differences either between diets or between breeds. Calmer animals also had a lower stress response during all preslaughter stages, regardless of the time in lairage. Transport did not imply psychological stress (cortisol) for any slaughter group, but physical stress was evident after transport in both groups through NEFA and CPK increases. Bruise incidences did not differ between lairage groups. The short lairage group did not have enough time to cope with the environment before slaughter, with the consequent deleterious effects on the carcass pH. Animals from the long lairage group had a higher metabolic response shown through NEFA values, but they had enough time to rest and recover overnight, reaching final pH values lower than 5.8, considered the upper limit of the normal range. According to this experiment, with pasture-based animals without fasting on the farm and after 3.5 h of transportation, a resting period of 15 h in lairage should be better than a 3-h one.

Head and neck squamous cell carcinoma (HNSCC), a prevalent cancer worldwide, has a high incidence of loco-regional dissemination, frequent recurrence, and lower 5-year survival rates. Current gold standard treatments for advanced HNSCC rely primarily on radiotherapy and chemotherapy but with limited efficacy and significant side effects. In this study, we characterized a novel 5-fluorouracil (5-FU) carrier composed of chitosan solution (CS) and polycaprolactone (PCL) microparticles (MPs) in HNSCC preclinical models. The designed MPs were evaluated for their size, morphology, drug entrapment efficiency (EE%) and in vitro drug release profile. The anti-cancer activity of 5-FU-loaded particles was assessed in HNSCC human cell lines (CAL27 and HSC3) and in a preclinical mouse model (AT84) utilizing cell proliferation and survival, cell motility, and autophagy endpoints. The results demonstrated a 38.57 % in 5-FU entrapment efficiency associated with reduced 5-FU in vitro release up to 96 h post-exposure. Furthermore, CS-decorated PCL MPs were able to promote a significant inhibition of cancer cell proliferation based on the metabolic and colony formation assays, in comparison to controls. In contrast, CS-decorated PCL MPs did not influence the pharmacological efficacy of 5-FU to inhibit in vitro cancer cell migration. Last, cell protein analysis revealed a significant increase of autophagy and cell death evaluated by LC3-II expression and PARP1 cleavage, respectively. In summary, these results support the potential utility of CS-decorated PCL MPs as an effective 5-FU-delivery carrier to improve HNSCC therapeutic management., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Hemispherectomy has an established role as a treatment of last resort in patients with unilateral hemispheric lesions suffering from refractory epilepsy., Methods: Seven patients were evaluated at our Epilepsy Unit. We compared the seizure outcome at 6 months, 1, 2, 5 years post-surgery, as well as at end follow-up (mean 7.1 years) using Engel classification. Reduction of antiepileptic drugs (AEDs) was also assessed utilizing equal time frames., Results: The mean age of seizure onset was 5.4 years. Engel I was achieved in 5 patients at 6 months (71.4%). Engel at 1 year was predicted by the Engel at 6 months (p=0.013) with a similar number of patients being classified as Engel I outcome. Engel at 2 years was also predicted by Engel at 6 months and at 1 year (p=0.030). At end follow-up only 3 patients (42.9%) remained categorized as Engel I outcome. There was a trend toward a stability in Engel classification. All patients with developmental causes for their epilepsy experienced some deterioration of the surgical outcomes. Conversely, all patients with acquired causes were stable throughout follow-up. Seizure outcome at 6 months was worse in the patients who had post-op complications (p=0.044). Adult and pediatric populations did not differ significantly in any tested variable., Conclusions: Hemispherectomy is a valuable resource for seizure control in properly selected patients. Engel patient's evolution could be predicted at 6 months interval. Hemispherectomy could be considered a useful attitude in difficult cases., (Copyright © 2021 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.)

The aim of this experiment was to evaluate the effect of different fattening systems from pasture to concentrate and temperament on animal welfare (AW) and meat quality (MQ). Eighty-four Hereford steers were randomly assigned to the following groups: T1, pasture (4% of animal live weight: LW); T2, pasture (3% LW) plus concentrate (0.6% LW); T3, pasture (3% LW) plus concentrate (1.2% LW); T4, an ad libitum concentrate treatment. Temperament was assessed by three individual tests: crush score, flight time, and exit speed, building a multicriterial temperament index (TIndex). The flight zone was also registered for each treatment. AW was assessed through the integration of indicators of productivity, physiology, and behavior, as well as by monitoring the health status within each treatment. Shear force was registered for MQ. Differences in average daily gain were due to the different energetic composition of the diets (T4 > T3 > T2 > T1) and were not attributable to animal welfare problems. Animals from T4 had the higher average daily gain (ADG) but welfare was negatively affected, being evident through physiological indicators, the restriction or deprivation of relevant behaviors, diet-related diseases, and mortality. T1, T2, and T3 did not appear to compromise animal welfare. However, strict preventive measures and monitoring should be taken during the habituation process and when using any new diet that includes concentrate, because of possible dietary diseases. Shear force values were lower in T1. None of the animals in our experiment were excitable or aggressive, but there was a positive response to handling in all treatments. In addition, regardless of diet, calmer animals had higher average daily gain and lower shear force values; thus, temperament appears to have a significant influence on productivity and meat quality.

Background: Brazil is an upper middle-income country in South America with the world's sixth largest population. Despite great advances in health-care services and cardiac surgical care in both its public and private health systems, little is known on the volume, outcomes, and trends of coronary artery bypass grafting (CABG) in Brazil's public health system., Objective: The aim of this study was to evaluate the outcome of CABG on the public health system from January 2008 to December 2017 through the database DATASUS., Methods: This study is based on publicly available material obtained from DATASUS, the Brazilian Ministry of Health's data processing system, on numbers of surgical procedures, death rates, length of stay, and costs. Only isolated CABG procedures were included in our study. We used the TabNet software from the DATASUS website to generate reports. The χ 2 test was used to compare death rates. A p < .05 was considered statistically significant., Results: We identified 226,697 CABG procedures performed from January 2008 to December 2017. The overall in-hospital mortality over the 10-year period was 5.7%. We observed statistically significant differences in death rates between the five Brazilian macro-regions. Death rates by state ranged from 2.6% to 13.1%. The national average mortality rate remained stable over the course of time., Conclusion: Over 10 years, a high volume of CABG was performed in the Brazilian Public Health System, with significant differences in mortality, number of procedures, and distribution of surgeries by region. Future databases involving all centers that perform CABG and carry out risk-adjusted analysis will help improve Brazilian results and enable policymakers to adopt appropriate health-care policies for greater transparency and accountability., (© 2021 Wiley Periodicals LLC.)

Structure-based molecular networking is useful as a dereplication strategy to identify known molecules, unknown close analogues, or compound families. On the other hand, the ligand fishing assay is a remarkable alternative to accelerate the screening process and to overcome the drawbacks of laborious experiments usually adopted in natural product research. The combination of these approaches contributes to high productivity in disclosing active metabolites and a decrease in lead time identification. To provide a valuable data base for the alkaloids of A. salzmannii bark herein we disclose thirty-one isoquinoline alkaloids including benzyltetrahydroisoquinolines, aporphines, proaporphines, and protoberberines. Among these, twenty-six have not been described for A. salzmannii including the unprecedented alkaloid N,O-dimethylcoclaurine N-oxide. In addition, norcoclaurine (1), norreticuline (13), N,O-dimethylcoclaurine N-oxide (15), and N-acetylasimilobine (24) are now reported for the first time as ligand for acetylcholinesterase., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Seasonality effects on the mineral profile of goats were evaluated. Fifty males were divided into two groups, one with mineral supplementation and one control. Seasonal evaluation was conducted during four periods: beginning, middle, and end of the dry period and middle of the rainy period. Rib and liver biopsies were performed, and blood was collected at each period to evaluate mineral accumulation. Ca, P, Cu, Fe, Mo, Zn, and Co concentrations were determined using inductively coupled plasma optical emission spectrometry after acid digestion. Normal Ca, P, and Mo; low Cu, Zn, and Co; and high Fe levels were observed in the diet. The young animals analyzed showed normal serum and bone Ca and P concentrations, suggesting no need for supplementation throughout the entire year under the conditions of this study. Iron showed high values throughout the year, being potentially dangerous especially owing to its antagonistic relationship with other elements. Cu and Zn deficiency in the diet was observed under the conditions of this study, requiring supplementation with values higher than those contained in the mineral supplement used in the middle and end of the dry period. The supply of specific mineral supplement formulated for animals farmed in the semiarid region is suggested and would reduce costs.

The aim of this study was to develop polymeric nanofibers for controlled administration of Amphotericin B (AmpB), using the solution centrifugation technique, characterizing its microstructural and physical properties, release rate, and activity against Leishmania and Candida species. The core-shell nanofibers incorporated with AmpB were synthesized by Solution Blow Spinning (SBS) and characterized by scanning electron microscopy (SEM), differential scanning calorimetry, X-Ray diffraction, and drug release assay. In vitro leishmanicidal and antifungal activity were also evaluated. Fibrous membranes with uniform morphology and smooth surfaces were produced. The intensity of the diffraction peaks becomes slightly more pronounced, assuming the increased crystallization in PLA/PEG at high AmpB loadings. Drug release occurred and the solutions with nanofibers to encourage greater incorporation of AmpB showed a higher concentration. In the results of the experiment with promastigotes, the wells treated with nanofibers containing concentrations of AmpB at 0.25, 0.5, and 1%, did not have any viable cells, similar to the positive control. Various concentrations of AmpB improved the inhibition of fungal growth. The delivery system based on PLA/PEG nanofibers was properly developed for AmpB, presenting a controlled release and a successful encapsulation, as well as antifungal and antileishmanial activity., (Copyright © 2020 Gonçalves, Rocha, Pires, Muniz, Maciel, de Lima, dos Santos, Batista, de Medeiros, de Medeiros, de Oliveira, Goulart, Bonan and Castellano.)

Head and neck cancer (HNC) is a complex and heterogeneous disease associated with high mortality and morbidity worldwide. Standard therapeutic management of advanced HNC, which is based on radiotherapy often combined with chemotherapy, has been hampered by severe long-term side effects. To overcome these side effects, tumor-selective nanoparticles have been exploited as a potential drug delivery system to improve HNC therapy. A combination of MEDLINE, EMBASE, Cochrane Oral Health Group's Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov from inception up to June 2020 was used for this systematic review. A total of 1747 published manuscripts were reviewed and nine relevant references were retrieved for analysis, while eight of them were eligible for meta-analysis. Based on these studies, the level of evidence about the efficacy of nanoformulation for HNC therapy on tumor response and adverse side effects (SAE) was low. Even though basic research studies have revealed a greater promise of nanomaterial to improve the outcome of cancer therapy, none of them were translated into clinical benefits for HNC patients. This systematic review summarized and discussed the recent progress in the development of targeted nanoparticle approaches for HNC management, and open-up new avenues for future perspectives.

Functionalized micro- and nano-sized magnetic beads (MBs) have been widely used as versatile supports for proteins, enzymes, and drugs. Immobilized protein on MB surfaces has been successfully applied for ligand fishing assays allowing for direct identification of active ligands from complex mixtures, such as natural products and synthetic libraries. MBs with different properties such as different core compositions, sizes, coatings, and surface modifications are available commercially. Studies have been conducted to understand the role of these properties for ligand fishing assays. Here we evaluated, for the first time, the effect of MB size on the ligand fishing assay for acetylcholinesterase from Electrophorus electricus (AChE). For this purpose, four commercially available amine-terminated magnetic particles with diameters ranging from 4.5 nm to 106 μm were evaluated to fish out galantamine, a well-known AChE inhibitor, from an aqueous solution. All MBs were efficient at using glutaraldehyde to covalently immobilize AChE. The particles with diameters of about 1 μm (small microparticles) presented a higher protein mass capacity per milligram of particle than did those with diameters of about 4.5 nm (nanoparticles) and those with diameters of about 106 μm (large microparticles). The influence of these supports on the produced AChE-MBs with regards to hydrolysis turnover and ligand fishing was evaluated and is fully discussed.

Regional metastasis is the single most important prognostic factor in oral squamous cell carcinoma (OSCC). Abnormal expression of N-myc downstream-regulated genes (NDRGs) has been identified to occur in several tumor types and to predict poor prognosis. In OSCC, the clinical significance of deregulated NDRG expression has not been fully established. In this study, NDRG1 relevance was assessed at gene and protein levels in 100 OSCC patients followed up by at least 10 years. Survival outcome was analyzed using a multivariable analysis. Tumor progression and metastasis was investigated in preclinical model using oral cancer cell lines (HSC3 and SCC25) treated with epidermal growth factor (EGF) and orthotopic mouse model of metastatic murine OSCC (AT84). We identified NDRG1 expression levels to be significantly lower in patients with metastatic tumors compared with patients with local disease only (P = 0.001). NDRG1 expression was associated with MMP-2, -9, -10 (P = 0.022, P = 0.002, P = 0.042, respectively) and BCL2 (P = 0.035). NDRG1 lower expression was able to predict recurrence and metastasis (log-rank test, P = 0.001). In multivariable analysis, the expression of NDRG1 was an independent prognostic factor (Cox regression, P = 0.013). In invasive OSCC cells, NDRG1 expression is diminished in response to EGF and this was associated with a potent induction of epithelial-mesenchymal transition phenotype. This result was further confirmed in an orthotopic OSCC mouse model. Together, this data support that NDRG1 downregulation is a potential predictor of metastasis and approaches aimed at NDRG1 signaling rescue can serve as potential therapeutic strategy to prevent oral cancer progression to metastasis., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The attempt to manage patients with acute myeloid leukemia as outpatients has become increasingly common due to high hospitalization costs, low availability for beds and patient preference. Publications on the subject are scarce, especially in low-income regions and the safety in this population remains to be determined. The present study aims to assess the safety of consolidation with high-dose cytarabine in the outpatient setting. Materials and Methods: We retrospectively analyzed 39 patients who underwent consolidation with high-dose cytarabine, between 2009 and 2018, at Ophir Loyola Hospital, in Belém, Brazil. Patients treated after 2015 were given high-dose cytarabine as outpatients due to the decision of medical staff. Results: Twenty-seven patients received 76 cycles of cytarabine as outpatients; males were 48.14% of the total population, with a median age of approximately 45 years. The occurrence of delay between cycles was significantly lower among outpatients (48.14% vs. 83.33%, p = 0.04). There was no difference in relapse rates, transfusion requirements and non-relapse mortality between both groups. Hospitalization was required in 40.74% of patients during outpatient cycles and 18.51% of blood cultures were positive for pathogens. Non-relapse mortality was significantly higher among patients above 50 years old and treated on an outpatient basis (44.4% vs. 5.60%, p = 0.03). Conclusion: High-dose cytarabine administration on an outpatient basis appears to be safe and effective in a low-income population at the Brazilian Amazon region, but toxicity seems to be increased for patients older than 50 years., (Copyright : © International Journal of Hematology-Oncology and Stem Cell Research & Tehran University of Medical Sciences.)

Introduction  The understanding of normal vocal production is essential to guide any voice professional as it is fundamental to understand the effects of the posterior glottal gap on the vocal quality. Objective  The aim of the present study was to verify the association between glottic closure, acoustic parameters, and some characteristics of the videolaryngostroboscopy of young women without vocal complaints nor laryngeal disorders. Methods  This is a cross-sectional study with 56 women between 20 and 30 years old who underwent videolaryngostroboscopy. The acoustic parameters of the vowel /a:/ were analyzed using the Praat software, Release 4.6.10 (Paul Boersman and David Weenik, Amsterdam, Netherlands). Statistical Analysis  The chi-squared, Fischer, and Kruskall-Wallis tests were applied, with 5% significance. Results  Significant occurrence of posterior glottal gap (85.71%, p  < 0.001), of normal vocal folds vibration amplitude (82.14%, p  < 0.001), and of absence of significant constriction of the laryngeal vestibule (98.21%, p  < 0.001); no significant association of the glottic closure with the vocal acoustic parameters; no significant association of glottic closure, vocal folds vibration amplitude, and constriction of the laryngeal vestibule. Conclusion  There was a predominance of posterior glottal gap, normal vocal folds vibration amplitude, and absence of laryngeal vestibule constriction, and no relation with the acoustic parameters, suggesting that the posterior glottal gap did not generate impact on the vocal production of the young adult women studied.

This work describes a new simultaneous on-flow dual parallel enzyme assay based on immobilized enzyme reactors (ICERs) with mass spectrometry detection. The novelty of this work relies on the fact that two different enzymes can be screened at the same time with only one single sample injection and in less than 6 min. The system consisted of two immobilized capillary enzyme reactors (ICERs). More specifically, the ICERs comprised two different enzymes that were accommodated in parallel and were placed between a liquid chromatography (LC) system and a mass spectrometer (MS). The resulting system could be adapted to other types of enzyme reactors with different supports. All the elements in the system were interfaced by means of two 10-port/two-position switching valves. Different tubing dimensions allowed us to monitor the activity of each enzyme independently during the same analysis. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) bioreactors were chosen as proof of concept. Acetylcholine (ACh) was used as substrate; the area of its protonated enzymatic hydrolysis product ion, choline, [M+H] + m/z 104.0, was monitored in the presence and absence of the standard cholinesterase inhibitor galantamine. This method proved to be an interesting tool for fast, simultaneous, and independent label-free dual enzyme inhibitor assay., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Secondary metabolites from natural products are a potential source of acetylcholinesterase inhibitors (AChEIs), which is a key enzyme in the treatment of many neurodegenerative diseases. Inspired by the reported activities of isoquinoline-derivative alkaloids herein we report the design, one step synthesis and evaluation by capillary enzyme reactor (ICER) of benzyl analogs ( 1a - 1e ) of the tetrahydroprotoberberine alkaloid stepholidine, which is abundant in Onychopetalum amazonicum . Docking analysis based on the crystal structure of Torpedo californica AChE ( Tc AChE) indicated that π-π interactions were dominant in all planned derivatives and that the residues from esteratic, anionic and peripheral subsites of the enzyme played key interaction roles. Due to the similarities observed when compared with galantamine in the AChE complex, the results suggest that ligand-target interactions would increase, especially for the N -benzyl derivatives. From a series of synthesized compounds, the alkaloids (7 R ,13a S )-7-benzylstepholidine ( 1a ), (7 S ,13a S )-7-benzylstepholidine ( 1b ), and ( S )-10- O -benzylstepholidine ( 1d ) are reported here for the first time. The on flow bioaffinity chromatography inhibition assay, based on the quantification of choline, revealed the N -benzylated compound 1a and its epimer 1b to be the most active, with IC 50 of 40.6 ± 1 and 51.9 ± 1 μM, respectively, and a non-competitive mechanism. The proposed approach, which is based on molecular docking and bioaffinity chromatography, demonstrated the usefulness of stepholidine as a template for the design of rational AChEIs and showed how the target-alkaloid derivatives interact with AChE., (Copyright © 2019 de Lima, Lima, Maciel, Valentim, Nunomura, Lima, Koolen, de Souza, Pinheiro, Cass and da Silva.)

Purpose: This study investigated the anti-Candida activity and the Shore A hardness of a tissue conditioner (Softone™) modified by incorporation of terpinen-4-ol and cinnamaldehyde., Material and Methods: Agar diffusion, microdilution, and mechanism of action methods were performed to determine to evaluate the antifungal activity of phytoconstituents. Then, phytoconstituents in varying concentrations were incorporated into the tissue conditioner. The anti-Candida effect of the modified conditioner was evaluated through agar punch well and biofilm formation methods. Shore A hardness of the experimental liners was evaluated after baseline, 24 h, 48 h, 4 days, and 7 days immersion on artificial saliva., Results: The phytoconstituents incorporated into Softone showed completely inhibited fungal growth in concentrations of 20-40% and did not present significant antifungal activity until their concentrations where higher than 5%. There were differences between non-modified Softone and M5, M10, C10, and T10% (p < 0.05). The groups containing 10-40% of cinnamaldehyde incorporated into Softone were able to completely inhibit the biofilm. Concentrations below 40% of terpinen-4-ol showed unsatisfactory biofilm inhibition. The T40% and C40% groups presented the lowest Shore A hardness values. Hardness values from groups T40% at 7 days (p = 0.476); C40% at 4 days (p = 0.058); and T20% (p = 0.058), C20% (p = 0.205), T30% (p = 0.154), and C30% (p = 0.874) after 48 h did not differ from the control group., Conclusions: Cinnamaldehyde incorporated into Softone inhibited Candida biofilm formation at concentrations of 10-40%, being more effective than terpinen-4-ol modification despite of halo inhibition observed by both products., Clinical Relevance: All modifications showed a very similar pattern of hardness being useful for clinical practice.

Objective: This study aimed to understand the relationship between the Clock Drawing Test (CDT) and decreased blood flow in mild cognitive impairment (MCI) patients, using single-photon emission computed tomography., Method: We characterized regional cerebral blood flow (rCBF) and the correlation with clinical variables and future conversion to dementia in 94 amnestic MCI patients. Blood perfusion data was correlated with the CDT (quantitative and qualitative scores) in order to evaluate their relationship and usefulness in predicting conversion to dementia., Results: MCI patients displayed reduced rCBF in brain areas including the caudate nucleus; the frontal, parietal, and temporal lobes; as well as the cerebral cortex and cerebellum. The decrease in rCBF was higher for patients who later developed dementia. At baseline, CDT scores of these patients correlated with hypoperfusion in cortical and subcortical areas typically affected in Alzheimer's disease (AD) median 3 years before developing dementia. CDT total score was significantly correlated with rCBF in the left temporal lobe and the putamen; the analysis of rCBF in Brodmann areas showed significant correlations between the several clock elements (face, numbers, and hands), underlying qualitative errors (stimulus-bound response and conceptual deficit), and rCBF, most significantly in the left inferior temporal gyrus, posterior entorhinal cortex, posterior cingulate cortex, left parahippocampal cortex, and left inferior prefrontal gyrus., Conclusions: This study showed that a quantitative score and a qualitative assessment of clock drawing (error analysis) corresponded to dysfunction in AD key areas at an early stage, supporting the CDT utility in the detection of prodromal AD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Bioactive glasses (BG) applications include tissue engineering for bone regeneration, coating for implants, and scaffolds for wound healing. BG can be conjugated to ions like silver, which might add some antimicrobial properties to this biomaterial. The immunomodulatory activity of ion-doped bioactive glasses particles was not investigated before. The aim of this work was to evaluate the cytotoxic and immunomodulatory effect of BG and silver-doped bioactive glass (BGAg) in human peripheral blood cells. BG and BGAg samples belonging to the system 58SiO 2 • (36-x)CaO · 6P 2 O 5 · xAg 2 O, where x = 0 and 1 mol%, respectively, were synthesized via sol-gel method and characterized. Cytotoxicity, modulation of cytokine production (TNF- α , IL-1 β , IL-6, IL-4, and IL-10), and oxidative stress response were investigated in human polymorphonuclear cells (PMNs) and peripheral blood mononuclear cells (PBMCs) cultures. Cell viability in the presence of BG or BGAg was concentration-dependent. In addition, BGAg presented higher PBMCs toxicity (LC50 = 0.005%) when compared to BG (LC50 = 0.106%). Interestingly, interleukin4 was produced by PBMCs in response to BG and BGAg in absence of phytohemagglutinin (PHA) and did not modulate PHA-induced cytokine levels. Subtoxic concentrations (0.031% for BG and 0.0008% for BGAg) did not change other cytokines in PBMCs nor reactive oxygen species (ROS) production by PMN. However, BG and BGAg particles decreased zymosan-induced ROS levels in PMN. Although ion incorporation increased BG cytotoxicity, the bioactive glass particles demonstrated a in vitro anti-inflammatory potencial. Future studies are needed to clarify the scavenger potential of the BG/BGAg particles/scaffolds as well as elucidate the effect of the anti-inflammatory potential in modulating tissue growth in vivo .

Background: In 2015, high rates of microcephaly were reported in Northeast Brazil following the first South American Zika virus (ZIKV) outbreak. Reported microcephaly rates in other Zika-affected areas were significantly lower, suggesting alternate causes or the involvement of arboviral cofactors in exacerbating microcephaly rates., Methods and Findings: We merged data from multiple national reporting databases in Brazil to estimate exposure to 9 known or hypothesized causes of microcephaly for every pregnancy nationwide since the beginning of the ZIKV outbreak; this generated between 3.6 and 5.4 million cases (depending on analysis) over the time period 1 January 2015-23 May 2017. The association between ZIKV and microcephaly was statistically tested against models with alternative causes or with effect modifiers. We found no evidence for alternative non-ZIKV causes of the 2015-2017 microcephaly outbreak, nor that concurrent exposure to arbovirus infection or vaccination modified risk. We estimate an absolute risk of microcephaly of 40.8 (95% CI 34.2-49.3) per 10,000 births and a relative risk of 16.8 (95% CI 3.2-369.1) given ZIKV infection in the first or second trimester of pregnancy; however, because ZIKV infection rates were highly variable, most pregnant women in Brazil during the ZIKV outbreak will have been subject to lower risk levels. Statistically significant associations of ZIKV with other birth defects were also detected, but at lower relative risks than that of microcephaly (relative risk < 1.5). Our analysis was limited by missing data prior to the establishment of nationwide ZIKV surveillance, and its findings may be affected by unmeasured confounding causes of microcephaly not available in routinely collected surveillance data., Conclusions: This study strengthens the evidence that congenital ZIKV infection, particularly in the first 2 trimesters of pregnancy, is associated with microcephaly and less frequently with other birth defects. The finding of no alternative causes for geographic differences in microcephaly rate leads us to hypothesize that the Northeast region was disproportionately affected by this Zika outbreak, with 94% of an estimated 8.5 million total cases occurring in this region, suggesting a need for seroprevalence surveys to determine the underlying reason., Competing Interests: The authors have declared that no competing interests exist.

Background: Hepatitis C is an important health problem. In Brazil, 1-2 million people are infected. Despite this expressive number, and the availability of very successful treatment, many patients remained undiagnosed mainly because of the asymptomatic nature of the infection., Objectives: To describe epidemiological characteristics of HCV-infected patients seen at referral centers in Brazil, the source of referral, and the time spanned to reach a reference center, in order to improve the identification of undiagnosed patients., Methods: Multicenter observational, cross-sectional study carried out in 15 centers of Brazil, between January/2016 and June/2017. Data of patients with a confirmed diagnosis (anti-HCV and HCV-RNA) were collected by interview using standard questionnaires and by review of charts., Results: Two thousand patients were included; 55.1% were male, mean age 58±11 years. Only 14.9% had higher education and 84.2% received up to five monthly minimum Brazilian wages (approximately US$260.00/month). The time between diagnosis and beginning of follow-up was 22.9 months. The most common reasons for testing were check-up (33.2%) and blood donation (19%). General practitioners diagnosed most of the patients (30.1%). Fibrosis stage was mainly evaluated by liver biopsy (61.5%) and 31.3% of the patients were cirrhotic at diagnosis., Conclusions: This multicenter Brazilian study showed that the mean time to reach a referral center for treatment was almost two years. Primary care physicians diagnoses most hepatitis C cases in the country. Population campaigns and medical education should be encouraged to intensify screening of asymptomatic individuals, considering the efficiency of check-ups in identifying new patients., (Copyright © 2019 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Subclinical hypocalcemia is a metabolic disorder characterised by a decrease in serum calcium (Ca) levels, with no clinical symptoms. The aim of this study was to determine the punctual prevalence of subclinical hypocalcemia in dairy cows, in the Sousa city micro-region, Paraíba state. Samples were collected from 29 dairy farms, consisting of 153 and 296 blood samples in the pre- and postpartum period respectively. In relation to the mineral supplementation profile, 89.25% of the properties use a commercial supplement. On average, 40.53% of lactating cows presented total serum Ca levels under the lower limit of 8.0 mg/dL, with an exclusive supplement of NaCl resulting in a higher percentage of cows, 61.11%, with the condition of subclinical hypocalcemia. For ionized Ca, the average prevalence of subclinical hypocalcemia was 21.16%. The prevalence of subclinical hypocalcemia for total serum Ca was 37.25 and 42.23% of cows in the pre- and postpartum period respectively. The type of mineral supplement did not influence (P > .05) total and ionized serum Ca levels in lactating cows. There was no significant difference (P > .05) for total and ionized serum Ca levels as a function of the reproductive period in lactating cows. Subclinical hypocalcemia was evident in the dairy cows under evaluation and occurred with an average punctual prevalence of 40.34%. Commercial supplement is the most common form of mineral mixture used; however, it was not able to promote an increase in the levels of total and ionized serum Ca levels due to errors in managing the supply.

The present study demonstrates the antifungal potential of chemically characterized essential oil (EO) of Cinnamomum zeylanicum Blume on Candida spp. biofilm and establishes its mode of action, effect on fungal growth kinetics, and cytotoxicity to human cells. The minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) values varied from 62.5 to 1,000 μ g/mL, and the effect seems to be due to interference with cell wall biosynthesis. The kinetics assay showed that EO at MICx2 (500 μ g/mL) induced a significant (p < 0.05) reduction of the fungal growth after exposure for 8 h. At this concentration, the EO was also able to hinder biofilm formation and reduce Candida spp. monospecies and multispecies in mature biofilm at 24 h and 48 h (p < 0.05). A protective effect on human red blood cells was detected with the EO at concentrations up to 750 μ g/mL, as well as an absence of a significant reduction (p > 0.05) in the viability of human red blood cells at concentrations up to 1,000 μ g/mL. Phytochemical analysis identified eugenol as the main component (68.96%) of the EO. C. zeylanicum Blume EO shows antifungal activity, action on the yeast cell wall, and a deleterious effect on Candida spp. biofilms. This natural product did not show evidence of cytotoxicity toward human cells.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are key cholinesterase enzymes responsible for the hydrolysis of acetylcholine into choline and acetic acid, an essential process for the restoration of the cholinergic neuron. The loss of cholinergic function in the central nervous system contributes to the cognitive decline associated with advanced age and Alzheimer's disease (AD). Inhibitions assays represent a significant role in the drug discovery process. Herein, we describe an improved label free method to screen and characterize new BChE ligands. The liquid chromatography system uses an immobilized capillary enzyme reactor (ICER) as a low affinity and high selectivity column coupled to a mass spectrometer (MS). The enzyme activity was evaluated by monitoring the choline's precursor ion [M + H] + m/z 104 for a brief period. The method was validated using two known cholinesterase inhibitors tacrine and galanthamine. The IC 50 values were 0.03 ± 0.006 μM and 0.88 ± 0.2 for tacrine and galanthamine respectively, and Ki was 0.11 ± 0.2 for galanthamine. The efficient combination of the huBChE-ICER with sensitive enzymatic assay detection such as MS, improved the reliable, fast identification of new ligands. Moreover, specific direct quantitation of the product contributes to the reduction of false positive and negative results., (Copyright © 2018. Published by Elsevier Inc.)

Background: and Purpose: Post-operative radiation therapy (PORT) is usually indicated for patients with breast cancer (BC) after neoadjuvant chemotherapy (NAC) and surgery. However, the optimal timing to initiation of PORT is currently unknown., Material and Methods: We retrospectively evaluated data from patients with BC who received PORT after NAC and surgery at our institution from 2008 to 2014. Patients were categorized into three groups according to the time between surgery and PORT: <8 weeks, 8-16 weeks and >16 weeks., Results: A total of 581 patients were included; 74% had clinical stage III. Forty-three patients started PORT within 8 weeks, 354 between 8 and 16 weeks and 184 beyond 16 weeks from surgery. With a median follow-up of 32 months, initiation of PORT up to 8 weeks after surgery was associated with better disease-free survival (DFS) (<8 weeks versus 8-16 weeks: HR 0.33; 95% CI 0.13-0.81; p = 0.02; <8 weeks versus >16 weeks: HR 0.38; 95% CI 0.15-0.96; p = 0.04) and better overall survival (OS) (<8 weeks versus 8-16 weeks: HR 0.22; 95% CI 0.05-0.90; p = 0.036; <8 weeks versus >16 weeks: HR 0.28; 95% CI 0.07-1.15; p = 0.08)., Conclusion: PORT started up to 8 weeks after surgery was associated with better DFS and OS in locally-advanced BC patients submitted to NAC. Our findings suggest that early initiation of PORT is critically important for these patients. However, the low numbers of patients and events in this study prevent us from drawing firm conclusions., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

We evaluated the antifungal and anti-biofilm activity, mechanism of action and cytotoxicity of chloramine T trihydrate (CAT) against Candida spp. The Minimum Inhibitory and Fungicidal Concentrations (MIC/MFC) of CAT were determined. Changes in CAT-treated C. albicans growth kinetics and micromorphology were evaluated, as well as the mechanism of action, and its effects on biofilm. Cytotoxicity was assessed by the hemolysis method. The data were analyzed by inferential statistics ( p ≤ 0.05). CAT showed antifungal activity against all strains, with MIC values ranging between 1.38 and 5.54 mmol/L (MIC 75% : 2.77 mmol/L). CAT demonstrated an immediate and sustained action on C. albicans growth kinetics, particularly at 2 × MIC. This compound likely acts on the cell wall and membrane permeability simultaneously and was found to cause changes in C. albicans micromorphology. Tha antibiofilm activity of CAT was similar to that of sodium hypochlorite ( p > 0.05) against mature biofilms. CAT was more effective than NaOCl in reducing mature biofilm upon 1-min exposure at 2 × MIC (24 h) and 4 × MIC (48 h) ( p < 0.05). Toxicological analysis revealed that CAT had hemolytic activity between 61 and 67.7% as compared to 100% by NaOCl. CAT has antifungal and anti-biofilm properties, probably acting on both cell wall and membrane permeability, and showed low toxicity in vitro., Competing Interests: The authors declare no conflict of interest.

Considerable interest in the relationship between biodiversity and disease has recently captured the attention of the research community, with important public policy implications. In particular, malaria in the Amazon region is often cited as an example of how forest conservation can improve public health outcomes. However, despite a growing body of literature and an increased understanding of the relationship between malaria and land use / land cover change (LULC) in Amazonia, contradictions have emerged. While some studies report that deforestation increases malaria risk, others claim the opposite. Assessing malaria risk requires examination of dynamic processes among three main components: (i) the environment (i.e. LULC and landscape transformations), (ii) vector biology (e.g. mosquito species distributions, vector activity and life cycle, plasmodium infection rates), and (iii) human populations (e.g. forest-related activity, host susceptibility, movement patterns). In this paper, we conduct a systematic literature review on malaria risk and deforestation in the Amazon focusing on these three components. We explore key features that are likely to generate these contrasting results using the reviewed articles and our own data from Brazil and Peru, and conclude with suggestions for productive avenues in future research.This article is part of the themed issue 'Conservation, biodiversity and infectious disease: scientific evidence and policy implications'., (© 2017 The Authors.)