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Abstract Electrostatic self-assembly was used to fabricate new smart multi-layer coatings, using a recombinant elastin-like polymer (ELP) and chitosan as the counterion macromolecule. The ELP was bioproduced, purified and its purity and expected molecular weight were assessed. Aggregate size measurements, obtained by light scattering of dissolved ELP, were performed as a function of temperature and pH to assess the smart properties of the polymer. The build-up of multi-layered films containing ELP and chitosan, using a layer-by-layer methodology, was followed by quartz-crystal microbalance with dissipation monitoring. Atomic force microscopy analysis permitted to demonstrate that the topography of the multi-layered films could respond to temperature. This work opens new possibilities for the use of ELPs in the fabrication of biodegradable smart coatings and films, offering new platforms in biotechnology and in the biomedical area.

Introduction: Bruxism is defined as a repetitive masticatory muscle activity that can manifest it upon awakening (awake bruxism-AB) or during sleep (sleep bruxism-SB). Some forms of both, AB and SB can be associated to many other coexistent factors, considered of risk for the initiation and maintenance of the bruxism. Although controversial, the term 'secondary bruxism' has frequently been used to label these cases. The absence of an adequate definition of bruxism, the non-distinction between the circadian manifestations and the report of many different measurement techniques, however, are important factors to be considered when judging the literature findings. The use (and abuse) of drugs, caffeine, nicotine, alcohol and psychoactive substances, the presence of respiratory disorders during sleep, gastroesophageal reflux disorders and movement, neurological and psychiatric disorders are among these factors. The scarcity of controlled studies and the complexity and interactions among all aforementioned factors, unfortunately, does not allow to establish any causality or temporal association with SB and AB. The supposition that variables are related depends on different parameters, not clearly demonstrated in the available studies., Objectives: This narrative review aims at providing oral health care professionals with an update on the co-risk factors and disorders possibly associated with bruxism. In addition, the authors discuss the appropriateness of the term 'secondary bruxism' as a valid diagnostic category based on the available evidence., Conclusion: The absence of an adequate definition of bruxism, the non-distinction between the circadian manifestations and the report of many different measurement techniques found in many studies preclude any solid and convincing conclusion on the existence of the 'secondary' bruxism., (© 2023 John Wiley & Sons Ltd.)

Objective: to evaluate the incompleteness of Mortality Information System (Sistema de Informações sobre Mortalidade - SIM) data on deaths from external causes (ECs) in the state of Rio Grande do Sul, Brazil, 2000-2019., Methods: This was an ecological study, using SIM data on all deaths from external causes and, specifically, from transport accident, homicides, suicides and falls; the analysis of the trend of incompleteness was performed by means of Prais-Winsten regression, with a 5% significance level., Results: A total of 146,882 deaths were evaluated; sex (0.1%), place of death (0.1%) and age (0.4%) showed the lowest incompleteness in 2019; the proportion of incompleteness showed a decreasing trend for the place of death and schooling, an increasing trend for marital status and a stable trend for age and race/skin color, among all types of death evaluated., Conclusion: the variables analyzed reached a high degree of completion; with the exception of marital status and schooling, for which unsatisfactory scores persisted for deaths from ECs, both total and by subgroups.

Infectious bovine rhinotracheitis (IBR) and bovine meningoencephalitis are caused by Bovine alphaherpesvirus (BoHV) types 1 and 5, which seriously threaten the global cattle industry. Vaccination to improve immunity is the most direct and effective means to prevent these conditions. Glycoprotein B (gB) is essential for the attachment of both viruses to permissive cells, and is a major target of the host immune system, inducing a strong humoral response. The aim of this study was to evaluate, in a murine model, the immune response of a candidate vaccine formulation composed of a chimeric BoHV-1 and BoHV-5 gB (DgB), expressed in Komagataella phaffii . The chimeric DgB vaccine adjuvanted with Montanide 50 ISA V2 or aluminum hydroxide was administered intramuscularly or subcutaneously. A control group and a group that received a commercial vaccine were inoculated subcutaneously. Higher titers of neutralizing antibodies against BoHV-1, BoHV-5, and a natural BoHV-1/5 recombinant strain were obtained with the oil-based candidate vaccine formulation administered intramuscularly. The results demonstrated that the chimeric DgB conserved important epitopes that were able to stimulate a humoral immune response capable of neutralizing BoHV-1, BoHV-5, and the recombinant strain, suggesting that the vaccine antigen is a promising candidate to be further evaluated in cattle.

Background: Bovine herpes virus (BoHV 1 and BoHV-5) are the causative agents of infectious bovine rhinotracheitis (IBR). IBR is responsible for important economic losses in the cattle industry. The envelope glycoprotein B (gB) is essential for BoHV infection of cattle's upper respiratory and genital tract. gB is one of the main candidate antigens for a potential recombinant vaccine since it induces a strong and persistent immune response., Results: In this study, gB of BoHV-1 and BoHV-5 was characterized in terms of function, structure, and antigenicity through bioinformatics tools. gB showed conserved sequence and structure, so, both domains named PH Like 1 and 2 domains of each virus were selected for the design of a bivalent vaccine candidate. The immunoinformatic study showed that these two domains have epitopes recognizable by B and T lymphocytes, followed by this, the cDNA domains from BoHV-1/5 gB (Domains-gB) were transformed into the yeast Komagataella phaffii GS115 (previously known as Pichia pastoris). A recombinant protein with molecular weight of about 110 kDa was obtained from the culture media. The vaccine candidate protein (Domains-gB) was recognized by a monoclonal antibody from a commercial ELISA kit used for IBR diagnostic, which may suggest that the epitopes are conserved of the entire infectious virus., Conclusion: Overall, it was shown that the recombinant domains of BoHV-1/5 gB have antigenic and immunogenic properties similar to the native gB. This vaccine candidate is promising to be used in future studies to assess its immunogenicity in an animal model., (© 2023. The Author(s).)

Background: Pentavalent antimonials (PAs) are the primary therapeutic option for American tegumentary leishmaniasis (ATL). However, the use of these drugs is complicated by adverse events (AEs), resistance and contraindications. Alternative therapies relative effectiveness is not well established., Objective: This study compared the effectiveness of liposomal amphotericin B (LAB) with intravenous meglumine antimoniate (NMG) in the treatment of ATL. We also analysed and compared associated AEs and treatment interruption rates., Methods: This was a retrospective cohort study from Brazil. The potential risk factors for the primary outcome were age, sex, total cutaneous lesion area, presence of mucosal lesions, AEs and treatment interruption. The primary outcome was lesion healing within 6 months of treatment. AEs and treatment interruption were also analysed. Multiple analytic strategies were employed to evaluate the reliability of the results., Results: Before propensity score (PS) matching, patients in the LAB group were older and had a higher frequency of mucosal lesions. The NMG group had a higher cure rate than the LAB group (cure rate 88% versus 55% respectively) in the adjusted analysis (relative risk (RR)=1.55 95% CI: 1.19 - 2.02) and after PS matching (RR=1.63 95% CI: 1.20 - 2.21). NMG group had a higher AE rate (event rate 52% versus 44%) in the adjusted analysis (RR= 1.61, 95% CI: 1.06 - 2.43, p=0.02), but this result was not observed after PS matching (RR= 0.87, 95% CI: 0.49 -1.52, p= 0.61)., Conclusions: We observed that the NMG group had a higher cure rate than the LAB group, with an equivocally higher EV rate in the adjusted analysis., 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 Barroso, Gonçalves, Barbosa, da Motta, Freire, Gomes and Sampaio.)

Malnutrition in heart failure (HF) is frequent and associated with a worse prognosis. Due to differences in investment and the profile of those assisted, the objective of this study was to evaluate the frequency of malnutrition in hospitalized patients with HF and its association with clinical outcomes in the public and private health systems. Methodology: A cross-sectional study, with 247 volunteers hospitalized with HF in three public hospitals and one private hospital in Aracaju, SE, Brazil. A subjective global nutritional assessment (SGA) and mini nutritional assessment (MNA) were performed. Results: Sample with 72.5% users of the public health system and 75.3% with malnutrition (public = 74.9%; private = 76.5%; p = 0.793). Regardless of the healthcare system, hospital stay (>14 days) was longer (p = 0.020) among those with malnutrition (48.4%) than well-nourished patients (29.5%). Malnutrition in the public system had higher mortality (7.5%; 5.8%; p < 0.001) and hospital transfer rate (21.1%; 0.0%; p < 0.001) than those in the private system. Death after discharge was observed only in the public system (p = 0.039). Conclusion: Malnutrition was frequent in both systems and was associated with longer hospital stays and, in the public hospital, in-hospital death and transfers.

Background: "The effective treatment of Heart Failure (HF) involves care with food intake. Recently, the Ministry of Health created the Brazilian Cardioprotective Diet and its dietary index, BALANCE, which assesses adherence to the standard's recommendations"., Methods: This observational prospective study is part of the Congestive Heart Failure Registry (VICTIM-CHF) of Aracaju/SE. Observations and data collection took place from April 2018 to February 2021. Sociodemographic and clinical aspects and food consumption were evaluated. Food intake was determined using the food frequency questionnaire. Foods were categorized using the BALANCE dietary index into green, yellow, blue and red food groups. The BALANCE dietary index was obtained using median and interquartile ranges, scores of the Mann-Whitney U test, and associations between clinical variables and the index, through linear regression., Results: Participants included 240 patients with HF (61.12 ± 1.06 years), who were assisted by the Unified Health System (67.5%). Individuals with a partner showed greater adherence to the green food group recommendations (0.09; 0.00-0.17). The lowest adherence to recommendations regarding the blue food group was observed in individuals with excess weight, who had a higher consumption of foods rich in animal protein (0.54; 0.38-0.78). As for the red food group (ultra-processed foods) the highest adherence was observed by patients with diabetes mellitus (0.41; 0.05-0.77). The greatest adherence to the yellow food group, and a higher score, was observed in patients with the smallest left ventricular systolic diameter (LVSD)., Conclusions: Being married was directly associated with the consumption of foods in the green group, while being overweight and having diabetes were inversely associated with adherence to the blue and red food groups, respectively. Greater adherence to the yellow food group recommendations was inversely associated with less change in the DSFVE.

Background: The high rates of hospitalization and mortality caused by Heart Failure (HF) have attracted the attention of health sectors around the world. Dietary patterns that involve food combinations and preparations with synergistic or antagonistic effects of different dietary components can influence the worsening and negative outcomes of this disease. Objectives: To describe the dietary patterns of patients hospitalized for HF decompensation and associate them with demographic, economic, and clinical factors, and the type of care provided in Sergipe. Materials and Methods: Cross-sectional study that is part of the Congestive Heart Failure Registry (VICTIM-CHF)” of Aracaju/SE. Prospective data collection took place with all patients hospitalized between April 2018 and February 2021 in cardiology referral hospitals, 2 public and 1 private. The data collected were sociodemographic, clinical, lifestyle, anthropometric and food consumption variables. Daily dietary intake was estimated by applying a semiquantitative food frequency questionnaire. The extraction of dietary patterns, by exploratory factor analysis, was performed after grouping the foods according to the nutritional value and form of preparation into 34 groups. To assess the association between the factorial scores for adherence to the standards and the variables studied, the Mann-Whitney U test was applied. Linear regressions were also performed, considering the dietary pattern (one for each pattern) as a dependent variable. Results: The study included 240 patients hospitalized for HF decompensation, most of them elderly (mean age 61.12 ± 1.06 years), male (52.08%) and attended by the Unified Health System—SUS (67.5%). Three dietary patterns were identified, labeled “traditional” (typical foods of the Brazilian northeastern population added to ultra-processed foods), “Mediterranean” (foods recommended by the Mediterranean diet) and “dual” (healthy foods combined with fast and easy-to-prepare foods like snacks, bread, sweets and desserts). Adherence to the “traditional” pattern was greater among men (p < 0.031) and non-diabetics (p < 0.003). The “Mediterranean” was more consumed by the elderly (p < 0.001), with partners (p = 0.001) and a lower income (p < 0.001), assisted by the SUS (p < 0.001) and without hypertension (p = 0,04). The “dual” diet pattern had greater adherence by the elderly (p < 0.001), self-declared non-black (p = 0.012), with higher income (p < 0.001), assisted in the private sector (p < 0.001) and with less impaired functional capacity (p = 0.037). It was also observed that being female (p = 0.031) and being older reduced the average scores of performing the “traditional” pattern (p = 0.002). Regarding the type of service, being from the public service reduced the average scores for adhering to the “dual” pattern (p = 0.008). Conclusions: Three dietary patterns representative of the population were found, called traditional, Mediterranean and dual, which were associated with demographic, economic and clinical factors. Thus, these standards must be considered in the development of nutritional strategies and recommendations in order to increase adherence to diets that are more protective against cardiovascular diseases.

Introduction : The Activities-specific Balance Confidence scale is the most used tool to quantify balance confidence, a psychological factor related to balance impairment among older adults. Objective : To investigate the validity and reliability of the original and short versions of the Brazilian Activities-specific Balance Confidence scales, to determine cutoff points for balance impairments and to identify the determinants of balance confidence of community-dwelling older adults. Methods : The validity of both versions of the scales was verified by correlating its results with postural balance, fear of falling and mobility (n = 105). Both scales were administered with a 30 min (interrater reliability, n = 158) and 1-week intervals (intrarater reliability, n = 105). Receiver operating characteristic curve was used to determine the cutoff points, and linear regression was applied to identify the determinants of balance confidence. Results : The Brazilian versions of the scale correlated to postural balance, fear of falling and mobility ( p < .05). Excellent interrater (α = 0.946, 95% CI: 0.902-0.976; α = 0.932, 95% CI: 0.918-0.960) and intrarater reliability (α = 0.946, 95% CI: 0.905-0.960; α = 0.952, 95% CI: 0.921-0.965) were found for the original and short versions.  Values of ≤67% (sensitivity: 81%, specificity: 77.4%) and ≤44% (sensitivity: 87.5%, specificity: 82.1%) were observed to identify balance impairments for the original and short versions of the scale. Physical inactivity, fear of falling, imbalance sensation, and number of falls are the main determinants of balance confidence. Conclusion : Both scales are valid and reliable to assess balance confidence. Cutoff points to identify balance impairments were determined and some factors may act as possible predictors of balance confidence.

Visceral leishmaniasis (VL) is a public health problem in Brazilian municipalities. As much as there is a planning of public policies regards VL in São Paulo State, new cases have been reported and spread. This paper aims to discuss how the Center for Zoonoses Control conducts its actions spatially in endemic city of Presidente Prudente, São Paulo State. Data are from the Municipal Health Department of Presidente Prudente, Adolfo Lutz Institute, and Brazilian Institute of Geography and Statistics. We spatially estimated the dog population per census tract and used geoprocessing tools to perform choropleth maps, spatial trends, and spatial autocorrelation. We found a spatial pattern of higher prevalence in the city's outskirt and a positive statistically significant spatial autocorrelation (I = 0.2, p-value < 0.000) with clusters of high-high relationships in the Northwest part of the city. Moreover, we identified a different direction in the path of the conducted serosurveys versus the canine VL trend, which stresses the fragility of the Center for Zoonoses Control actions to control the disease. The Center for Zoonoses Control always seems to chase the disease. The spatial analysis may be useful for rethinking how the service works and helps in public policies.

Osteoporosis therapies leveraging bisphosphonates and mineral components (e.g., magnesium, calcium, and strontium) have been raising attention because of their potential for managing this ever-growing disease. The administration of multicomponent therapeutics (combined therapy) in elderly patients is complex and suffers from low patient adherence. Herein, we report an all-in-one combination of four antiosteoporotic components into a new family of coordination complexes: [M 2 (H 4 alen) 4 (H 2 O) 2 ]·1.5H 2 O [where M 2+ = Mg 2+ ( 1 ), (Mg 0.535 Ca 0.465 ) 2+ ( 2 ) and (Mg 0.505 Ca 0.450 Sr 0.045 ) 2+ ( 3 )]. These solid-state complexes were prepared, for the first time, through microwave-assisted synthesis. It is demonstrated that the compounds are capable of releasing their antiosteoporotic components, both in conditions that mimic the path along the gastrointestinal tract and in long periods under physiological conditions (pH ∼7.4). More importantly, when administered in low concentrations, the compounds did not elicit a cytotoxic effect toward liver, kidney, and osteoblast-like cell lines. Besides, it is important to highlight the unique coordination complex with four bone therapeutic components, [(Mg 0.505 Ca 0.450 Sr 0.045 ) 2 (H 4 alen) 4 (H 2 O) 2 ]·1.5H 2 O ( 3 ), which significantly promoted osteoblast metabolic activity up to ca. 1.4-fold versus the control group. These findings bring this type of compounds one-step closer to be considered as an all-in-one and more effective treatment for managing chronic bone diseases, prompting further research on their therapeutic properties.

Background: Dentists are exposed to contamination by SARS-CoV-2 due to dental interventions, leading to a state of alert and potential risk of negative impact in mental health and sleep quality, associated with Temporomandibular Disorder (TMD) and bruxism., Objective: to evaluate the psychosocial status, sleep quality, symptoms of TMD, and bruxism in Brazilian dentists (DSs) during the COVID-19 pandemic., Methodology: The sample (n=641 DSs) was divided into three groups (quarantined DSs; DSs in outpatient care; and frontline professionals), which answered an electronic form containing the TMD Pain Screening Questionnaire (Diagnostic Criteria for Temporomandibular Disorders - DC/TMD), the Pittsburgh Sleep Quality Index (PSQI), the Depression, Anxiety and Stress Scale (DASS-21), and the sleep and awake bruxism questionnaire. ANOVA test and Mann Whitney post-test were used, with Bonferroni adjustment (p<0.016) and a 95% confidence level., Results: Probable TMD was found in 24.3% (n=156) of the participants, while possible sleep and awake bruxism were diagnosed in 58% (n=372) and 53.8% (n=345) of them, respectively. Among all variables evaluated, only symptoms of depression were significantly greater in the quarantined DSs group when compared to those who were working at the clinical care (p=0.002). Working DSs were significantly less likely (OR=0.630, p=0.001) to have depressive symptoms. Those who were not worried or less worried about the pandemic were less likely to experience stress (OR=0.360), anxiety (OR=0.255), and poor sleep quality (OR=0.256). Sleep had a strong positive and moderate correlation with psychological factors on frontline workers and DSs in outpatient care, respectively., Conclusion: The results suggest confinement may have a more negative impact on the life of DSs than the act of being actively working. The concern about Covid-19 and poor sleep quality was significantly prevalent and may negatively affect the quality of life of DSs. Thus, further research on the topic is needed.

The present review describes the various roles of cyclodextrins (CDs) in vaccines against viruses and in antiviral therapeutics. The first section describes the most commonly studied application of cyclodextrins-solubilisation and stabilisation of antiviral drugs; some examples also refer to their beneficial taste-masking activity. The second part of the review describes the role of cyclodextrins in antiviral vaccine development and stabilisation, where they are employed as adjuvants and cryopreserving agents. In addition, cyclodextrin-based polymers as delivery systems for mRNA are currently under development. Lastly, the use of cyclodextrins as pharmaceutical active ingredients for the treatment of viral infections is explored. This new field of application is still taking its first steps. Nevertheless, promising results from the use of cyclodextrins as agents to treat other pathologies are encouraging. We present potential applications of the results reported in the literature and highlight the products that are already available on the market.

Bisphosphonates, used for a long time in osteoporosis management, are currently the target of intensive research, from pre-formulation studies to more advanced stages of clinical practice. This review presents an overview of the contributions of this family of compounds to human health, starting with the chemistry and clinical uses of bisphosphonates. Following this, their pharmacology is described, highlighting administration-borne handicaps and undesirable effects. The last three sections of the review describe the research efforts that seek to curb delivery-related issues and expand bisphosphonate use. Innovative routes and strategies of administration, such as nano-encapsulation for oral intake or injectable cements for local or in-bone delivery are presented, as well as the latest results of case studies or preclinical studies proposing new therapeutic indications for the clinically approved bisphosphonates. Finally, a selection of anti-infectious bisphosphonate new drug candidates is shown, with focus on the molecules reported in the last two decades.

Background and Objective: The routine practice of self-medication of blood pressure (BP) not oriented with pulse devices may not be precisely useful in the control of BP and can lead the patient to self-medicate in error. Thus, we need to evaluate the non-oriented self-assessment of BP in real-life circumstances in hypertensive patients. The objective of this study was to evaluate in hypertensive patients the association of BP self-measurement with its control, as well as the presence of anxiety disorders, the occurrence of unscheduled visits to the emergency room, and self-medication. Materials and Methods: An observational study was carried out with 1000 hypertensive volunteers (age: 61.0 ± 12.5). Using a questionnaire, sociodemographic and clinical data on BP control were collected. Anxiety was assessed by the State-Trait Anxiety Inventory (STAI). Results: The group that performed non-oriented self-measurement of BP, showed that they had higher frequencies of self-medication (57.9%, p < 0.05) and more unscheduled visits to the emergency room (68%, p < 0.05). In addition, a lower level of BP control (46.8%, p < 0.05) was associated with higher levels of anxiety (52.3%, p < 0.05) in the group that performed non-oriented self-measurements of BP. Conclusion: The practice of non-oriented self-assessment of BP was associated with negative factors such as high levels of anxiety and higher frequencies of self-medication and unscheduled emergency visits.

Osteoporosis, Paget's disease and osteosarcoma are a few examples of bone tissue disorders that affect millions of people worldwide. These conditions can strictly limit the lifestyle of patients and may even lead to their demise. To prevent this or, at least, try to manage the situation, there are several treatments available on the market. Notwithstanding, research has been driven by the possibility to improve the existing therapies, as well as to find new approaches that could better respond to these diseases. In this Review the path is shown through which, in recent years, coordination compounds have been prepared and manufactured to be applied in the management of bone tissue disorders. Starting with the design and preparation of the coordination compounds with various dimensionalities, two approaches have been used: (1) they are prepared as three-dimensional cages that can act as delivery systems for therapeutic substances, or (2) they are constructed/prepared from compounds with intrinsic therapeutic properties. Following this, several strategies have been explored to manufacture the effective delivery to the patients. The versatility of coordination compounds has allowed their use in the preparation of drug tablets, coatings for titanium implants, or even scaffolds for bone tissue engineering. In the end, it becomes clear that these compounds can be a valuable approach to reach a better treatment for bone tissue disorders. Nonetheless, along the road, a few bumps have appeared concerning the therapeutic profile, such as the effect of the structural arrangement or particle size., (© 2020 Wiley-VCH GmbH.)

Thrombin triggers cellular responses that are crucial for development and progression of cancer, such as proliferation, migration, oncogene expression and angiogenesis. Thus, biomolecules capable of inhibiting this protease have become targets in cancer research. The present work describes the in vitro antitumor properties of a chondroitin sulfate with anti-thrombin activity, isolated from the Litopenaeus vannamei shrimp (sCS). Although the compound was unable to induce cytotoxicity or cell death and/or cell cycle changes after 24 h incubation, it showed a long-term antiproliferative effect, reducing the tumor colony formation of melanoma cells by 75% at 100 μg/mL concentration and inhibiting the anchorage-independent colony formation. sCS reduced 66% of melanoma cell migration in the wound healing assay and 70% in the transwell assay. The compound also decreased melanin and TNF-α content of melanoma cells by 52% and 75% respectively. Anti-angiogenic experiments showed that sCS promoted 100% reduction of tubular structure formation at 100 μg/mL. These results are in accordance with the sCS-mediated in vitro expression of genes related to melanoma development (Cx-43, MAPK, RhoA, PAFR, NFKB1 and VEGFA). These findings bring a new insight to CS molecules in cancer biology that can contribute to ongoing studies for new approaches in designing anti-tumor therapy., Competing Interests: Declaration of competing interest The authors state that they have no conflict of interest., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Theoretical and analytical thermal and electrical properties are studied through the 2,7-Di([1,1'-biphenyl]-4-yl)-9H-fluorene aromatic system as a prototype of a molecular switch. Variations of the dihedral angles between the two Benzene rings at each end of the molecule have been considered, thus determining the dependence on the structural variation of the molecule when the aromatic system is connected between metal contacts. The molecule is modeled through a Tight-Binding Hamiltonian where-from the analytical process of decimation and using Green's functions-the probability of transmission ( T ) is calculated by using the Fisher-Lee relationship. Consequently, the thermal and electrical transport properties such as I - V curves, quantum noise ( S ), Fano factor ( F ), electrical conductance ( G ), thermal conductance ( κ ), Seebeck coefficient ( Q ), and merit number ( Z T ) are calculated. The available results offer the possibility of designing molecular devices, where the change in conductance or current induced by a stereoelectronic effect on the molecular junctions (within the aromatic system) can produce changes on the insulating-conductive states.

Bisphosphonates (BPs), well-known medicinal compounds used for osteoporosis management, are currently the target of intensive research, from basic pre-formulation studies to more advanced stages of clinical practice. The high demand by the pharmaceutical industry inherently requires an easy, efficient and quick preparation of BPs. Current synthetic procedures are, however, still far from ideal. This work presents a comprehensive compilation of reports on the synthesis of the commercially available bisphosphonates that are pharmaceutical active ingredients. Current limitations to the conventional synthesis are assessed, and paths towards their improvement are described, either through the use of alternative solvents and/or by selecting appropriate ratios of the reactants. Innovative processes, such as microwave-assisted synthesis, are presented as more environmental-friendly and effective methods. The main advantages and setbacks of all syntheses are provided as a way to clarify and promote the development of simpler and improved procedures. Only in this way one will be able to efficiently respond to the future high demand of BPs, mostly due to the increase in life span in occidental countries.

Most cancers have lost a critical DNA damage response (DDR) pathway during tumor evolution. These alterations provide a useful explanation for the initial sensitivity of tumors to DNA-targeting chemotherapy. A striking example is dysfunctional homology-directed repair (HDR), e.g., due to inactivating mutations in BRCA1 and BRCA2 genes. Extensive efforts are being made to develop novel targeted therapies exploiting such an HDR defect. Inhibitors of poly(ADP-ribose) polymerase (PARP) are an instructive example of this approach. Despite the success of PARP inhibitors, the presence of primary or acquired therapy resistance remains a major challenge in clinical oncology. To move the field of precision medicine forward, we need to understand the precise mechanisms causing therapy resistance. Using preclinical models, various mechanisms underlying chemotherapy resistance have been identified. Restoration of HDR seems to be a prevalent mechanism but this does not explain resistance in all cases. Interestingly, some factors involved in DNA damage response (DDR) have independent functions in replication fork (RF) biology and their loss causes RF instability and therapy sensitivity. However, in BRCA-deficient tumors, loss of these factors leads to restored stability of RFs and acquired drug resistance. In this review we discuss the recent advances in the field of RF biology and its potential implications for chemotherapy response in DDR-defective cancers. Additionally, we review the role of DNA damage tolerance (DDT) pathways in maintenance of genome integrity and their alterations in cancer. Furthermore, we refer to novel tools that, combined with a better understanding of drug resistance mechanisms, may constitute a great advance in personalized diagnosis and therapeutic strategies for patients with HDR-deficient tumors., (Copyright © 2020 Liptay, Barbosa and Rottenberg.)

Objectives: To assess patients with and without temporomandibular disorders (TMD) infrared thermography according to the differences in thermal radiance using quantitative sensitivity and specificity tests; and to evaluate the thermal asymmetry and the correlation of the thermal intensity with the intensity of pain upon palpation., Methods: This cross-sectional study performed a quantitative evaluation of clinical and thermographic examinations. The volunteers were evaluated for the presence of TMD using RDC/TMD (Diagnostic Research Criteria for Temporomandibular Disorders), and were divided into two groups: TMD group ( n = 45); control group ( n = 41), composed of volunteers without TMD, according to the Fonseca Anamnestic Index. The images were assessed for selected regions of interest for the masseter, anterior temporal and TMJ muscles. The mean values ​​of the areas of both groups were compared under the receiver operating characteristic curve. Spearman correlation analysis (non-parametric data) between pain level and mean temperature, by region, and the Pearson's χ 2 test was used to verify the association between the presence of temperature and pain asymmetry. The level of significance was set at p < 0.05., Results: Both Groups, with and without TMD, presented with absolute and non-dimensional mean temperature without statistical differences ( p >0.05). When correlating temperature with intensity of pain upon palpation, a negative correlation was observed for the masseter muscle., Conclusion: Infrared Thermography resulted in low area under the curve, making it difficult to differentiate TMD via thermographic analysis. The intensity of pain upon palpation in patients with TMD may be accompanied by a decrease in local temperature.

In this work, we used the rigid tetrapodal organic linker, [1,1'-biphenyl]-3,3',5,5'-tetrayltetrakis(phosphonic acid) (H 8 btp), for the preparation of two lanthanide-organic framework families of compounds: layered [Ln 7 (H 5 btp) 4 (H 5.5 btp) 2 (H 6 btp) 2 (H 2 O) 12 ]∙23.5H 2 O∙MeOH [where Ln 3+ = Eu 3+ ( 1Eu ) and Gd 3+ ( 1Gd )], prepared using microwave-irradiation followed by slow evaporation; 3D [Ln 4 (H 3 btp)(H 4 btp)(H 5 btp)(H 2 O) 8 ]∙3H 2 O [where Ln 3+ = Ce 3+ ( 2Ce ), Pr 3+ ( 2Pr ), and Nd 3+ ( 2Nd )], obtained from conventional hydro(solvo)thermal synthesis. It is shown that in this system, by carefully selecting the synthetic method and the metal centers, one can increase the dimensionality of the materials, also increasing structural robustness (particularly to the release of the various solvent molecules). Compound 1 is composed of 2D layers stacked on top of each other and maintained by weak π-π interactions, with each layer formed by discrete 1D organic cylinders stacked in a typical brick-wall-like fashion, with water molecules occupying the free space in-between cylinders. Compound 2, on the other hand, is a 3D structure with small channels filled with crystallization water molecules. A full solid-state characterization of 1 and 2 is presented (FT-IR spectroscopy, SEM microscopy, thermogravimetric studies, powder X-ray diffraction and thermodiffractometry). The photoluminescence of 1Eu was investigated.

A one-dimensional ladder-type coordination polymer, poly[[(μ 2 -hydroxido)(μ 2 -1 H -pyrazole-3,5-di-carboxyl-ato)gallium(III)] monohydrate], [Ga(C 5 H 2 N 2 O 4 )(OH)(H 2 O)] n or [Ga(HPDC)(OH)(H 2 O)] n , I , isotypic with a V 3+ coordination polymer previously reported by Chen et al. [ J. Coord. Chem. (2008). 61 , 3556-3567] was prepared from Ga 3+ and pyrazole-3,5-di-carb-oxy-lic acid monohydrate (H 3 PDC·H 2 O). Compound I was isolated using three distinct experimental methods: hydro-thermal (HT), microwave-assisted (MWAS) and one-pot (OP) and the crystallite size should be fine-tuned according to the method employed. The coordination polymeric structure is based on a dimeric Ga 3+ moiety comprising two μ 2 -bridging hydroxide groups, which are inter-connected by HPDC 2- anionic organic linkers. The close packing of individual polymers is strongly directed by the supra-molecular inter-actions, namely several O-H⋯O and N-H⋯O hydrogen-bonding inter-actions., (© Simões et al. 2019.)

Oxaliplatin is a third-generation platinum drug commonly used as the first line treatment of metastatic colorectal cancer. Oxaliplatin-based anticancer regimens course with dose-limiting neurotoxicity. The pharmacological strategies used to manage such side effect are not totally effective. Metformin is an anti-diabetic drug that is described to negatively modulate painful diabetic neuropathy. Then, this study aimed to assess the effect of metformin in the oxaliplatin-induced peripheral sensory neuropathy in mice. For that purpose, Swiss male mice were injected with oxaliplatin (1, 2 or 4 mg/kg, i.v., twice a week with a total of nine injections) alone or in combination with daily administration of metformin (250 mg/kg, p.o.). Thermal and mechanical nociceptive tests were performed once a week for five weeks. Then, the animals were euthanized on day 35 post-first injection of oxaliplatin and the dorsal root ganglia were harvested for the assessment of c-Fos and ATF3 expressions. Oxaliplatin caused a nociceptive response accompanied by the increased expression of c-Fos and ATF3 in the dorsal root ganglia and spinal cord. In addition, the oxaliplatin-associated nociception was significantly attenuated by metformin (P < 0.05), which also reduced the expression of c-Fos and ATF3 (P < 0.05). Therefore, metformin protected from the peripheral sensory neuropathy induced by oxaliplatin, which was confirmed by the reduction of c-Fos and ATF3 expression, two known neuronal activation and damage markers, respectively., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Montelukast (MLK), an oral antiasthmatic drug with growing use, requires special care in formulation and storage to avoid its degradation by action of light and water. This work investigates the increase in the stability of montelukast as the effect of molecular encapsulation with gamma-cyclodextrin (γ-CD) by means of a solvent-free method, cogrinding. As a first step, a 1:1 preferred stoichiometry is established for this hostguest system using a combination of molecular modeling and the continuous variation method. The solid 1:1 inclusion compound, γ-CD·MLK, is obtained by 2 comilling procedures. For comparison purposes, γ-CD·MLK is also prepared by a classical codissolution procedure and isolated by freeze-drying. Products were characterized by powder X-ray diffraction, 13 C{ 1 H} CP-MAS NMR, scanning electron microscopy, Fourier-transform infrared spectroscopy, thermogravimetry, and differential scanning calorimetry, which confirm inclusion, demonstrate the formation of amorphous products by comilling, and highlight the importance of the amorphous nature of the starting materials for the stability of the comilled final product. The dissolution profile of montelukast when released from the comilled products shows equivalent concentrations to those obtained with the same mass of the pure drug, with the extra advantage of keeping the solution stability (unaltered concentration) for longer periods., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Zebrafish have a high capacity to replace lost neurons after brain injury. New neurons involved in repair are generated by a specific set of glial cells, known as ependymoglial cells. We analyze changes in the transcriptome of ependymoglial cells and their progeny after injury to infer the molecular pathways governing restorative neurogenesis. We identify the aryl hydrocarbon receptor (AhR) as a regulator of ependymoglia differentiation toward post-mitotic neurons. In vivo imaging shows that high AhR signaling promotes the direct conversion of a specific subset of ependymoglia into post-mitotic neurons, while low AhR signaling promotes ependymoglial proliferation. Interestingly, we observe the inactivation of AhR signaling shortly after injury followed by a return to the basal levels 7 days post injury. Interference with timely AhR regulation after injury leads to aberrant restorative neurogenesis. Taken together, we identify AhR signaling as a crucial regulator of restorative neurogenesis timing in the zebrafish brain., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

TiO 2 is a common inorganic filter used in sunscreens due to its photoprotective effect on the skin against UV radiation. However, the use of this kind of material in cosmetics is limited by its inherent photocatalytic activity. It is known that coating on TiO 2 surface can improve some features. Although, many of the methodologies used for this purpose are still laborious and time-consuming. Thus, this work reports a novel, easy, cheap and fast strategy to coat TiO 2 particles by using a sonochemistry approach, aiming to decrease photocatalytic activity and to enhance colloidal stability. For this proposal, SiO 2 , Al 2 O 3 , ZrO 2 and sodium polyacrylate (PAANa) were used to tune the surface of commercial TiO 2 particles and they were applied in a sunscreen formulation. The samples were characterized by XRPD, FT-IR, DLS, EDS, SEM and TEM. The photocatalytic activity and UV-shielding ability were also evaluated. The sunscreen formulations were prepared and characterized by zeta potential, DLS, and Sun Protection Factor (SPF). FT-IR, EDS, and charge surface of the particles confirmed the success of the sonochemistry coating. Additionally, TiO 2 @Al 2 O 3 , TiO 2 @SiO 2 and TiO 2 @PAANa show a lower photocatalytic activity than original TiO 2 with similar UV-shielding ability. The sunscreens produced with the coated TiO 2 have similar SPF to the one with commercial TiO 2 . Specifically, the sunscreen with TiO 2 @PAANa shows an increase in colloidal stability. Herein, the incorporation of the sonochemical-coated TiO 2 particles in sunscreen formulations may produce sunscreens with better aesthetic appearance and a greater health security due to its lower free radicals production., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This study verified the occurrence of dental sensitivity in patients submitted to a 35% hydrogen peroxide based product (Whiteness HP Maxx 35% - FGM), skin cold sensation threshold (SCST) and its influence on dental sensitivity. Sixty volunteers were divided into 4 groups (n = 15), according to SCST (low: GI and GIII, and high: GII and IV) and bleaching treatment (hydrogen peroxide: GI and GII, and placebo: GIII and GIV). SCST was determined in the inner forearm for 6 different times using a neurosensory analyzer, the TSA II (Medoc Advanced Medical Systems, Ramat Yishai, Northern District, Israel). Dental sensitivity measurements were performed 10 different times using a thermal stimulus and an intraoral device attached to TSA II, positioned in the buccal surface of the upper right central incisor. Spontaneous dental sensitivity was also determined using the Visual Analogue Scale (VAS). Data were submitted to Student's t-test and Pearson's Correlation Test (α=0.05). SCST remained the same during bleaching treatment. Distinct responses of dental sensitivity were found in patients with low and high SCST during the first and third bleaching session (p≤0.05). The teeth submitted to the bleaching treatment became more sensitive to cold than those treated with placebo. Moreover, data obtained with TSA and VAS presented moderate correlation. Bleaching treatment increased dental sensitivity and skin cold sensation threshold might represent a determining factor in this occurrence, since low and high SCST patients had different responses to the thermal stimulus in the teeth.

Background/aims: Definitive polycystic ovary syndrome (PCOS) diagnosis should exclude thyroid dysfunctions. The purpose of the study is to examine the impact of subclinical hypothyroidism on the characteristics of PCOS patients., Methods: A meta-analysis of the published observational studies was conducted. Medline, Scopus, and Cochrane database search was performed to identify the studies that compared euthyroid PCOS and subclinical hypothyroidism (SCH)-PCOS patients. A total of 9 studies were selected, totalizing the inclusion of 1,537 euthyroid PCOS and 301 SCH-PCOS. The data were expressed as raw mean difference and standard error, using the random-effects model. Heterogeneity among studies was examined using the Cochran's test (Q) and I2 statistics., Results: Anthropometrical parameters were similar in both groups. Total cholesterol (TC) and triglyceride (TG) were higher in SCH-PCOS (p = 0.036 and p = 0.012). High-density lipoprotein cholesterol was lower in the SCH-PCOS group (p = 0.018). Fasting glucose was lower in euthyroid PCOS (p = 0.022). All androgen levels were similar in both group (p > 0.05 for all)., Conclusion: TC, TG and fasting glucose were higher in SCH-PCOS patients. Because of the heterogeneity among studies, some summarized results should be interpreted with caution. Consistent data for future studies addressing PCOS diagnosis are provided., (© 2017 S. Karger AG, Basel.)

The present study aimed to assess the accuracy of linear measurements performed with two software packages in multislice (MSCT) and cone beam (CBCT) computed tomography (CT) images. The sample consisted of 10 human mandibles marked standardly 8 times with metallic orthodontic wires. The mandibles underwent both MSCT and CBCT scanning and were measured linearly and digitally with two software packages, namely Studio 3.1® (Anne Solutions®, SP, Brazil) (ST) and Implant Viewer 2.817® (Anne Solutions®, SP, Brazil) (IV). The linear measurements were the mandibular height (MH) and width (MW), and the distance from the alveolar ridge to the mandibular canal (AC). To validate the measurements, the mandibles were sectioned in the marked regions and measured with a digital caliper. Statistically significant differences were not observed between the measurements (MH, MW, and AC) taken digitally with the two software packages from images obtained from the two scanning modalities (MSCT and CBCT) and the measurements taken manually with a digital caliper (p>0.05). MSCT and CBCT images measured digitally with ST and IV software packages resulted in reliable outcomes when compared to measurements obtained manually. Both software and imaging modalities are reliably useful for planning surgical procedure in the dental practice.

Background: The purpose of the study was to examine whether patients with subclinical hypothyroidism (SCH) should be excluded before making a diagnosis of polycystic ovary syndrome (PCOS)., Methods: Seven hundred sixteen patients, 462 with true PCOS, 31 with PCOS-SCH, and 223 normal cycling women were enrolled. Clinical, metabolic, and hormonal parameters among the groups were investigated. Continuous variables were compared by one-way analysis of variance. Proportions were compared using Z test. Fisher test was used to compare categorical variables. Simple correlation was performed using Spearman's coefficient. Correlation between thyroid stimulating hormone (TSH) and dependent variables were performed using backward multiple regression. The significance level was set at 0.05., Results: True polycystic ovary and polycystic ovary with subclinical hypothyroidism patients presented similar anthropometrical parameters. C-peptide was higher in polycystic ovary patients than in the other groups (p=0.014). Prevalence of glucose intolerance (p=0.186) and insulin resistance (p=0.293) was not statistically different in polycystic ovary and polycystic ovary with subclinical hypothyroidism. TSH levels showed positive correlation with lean body mass (p=0.032), total cholesterol (p=0.046, insulin (p=0.048) and prolactin (p=0.047). Backward multiple regression model retained TC, insulin, and PRL as predictors of TSH levels (p=0.011)., Conclusion: Anthropometric parameters and ovary morphology were similar in both PCOS and PCOS-with-SCH patients. Regarding hormones, only C-peptide was higher in PCOS group. TSH correlated with total cholesterol, insulin, and prolactin. Before PCOS diagnosis, the exclusion criterion thyroid dysfunction should be standardized and subclinical hypothyroidism should not exclude a diagnosis of PCOS.

The present study evaluates the acute toxicity of synthetic grape, plum and orange flavourings in root meristem cells of Allium cepa at the doses of 3.5, 7.0 and 14.0 mL/kg and exposure times of 24 and 48 h, and in bone marrow erythrocytes of mice treated orally for seven days with 0.5, 1.0, 2.0, 5.0 and 10.0 mL/kg of flavouring. The results of the plant test showed that grape, plum and orange flavourings, at both exposure times, inhibited cell division and promoted the formation of a significant number of micronuclei and mitotic spindle changes. These alterations were observed in at least one exposure time analysed, demonstrating a significant cytotoxic, genotoxic and mutagenic activity. In mouse bioassay, animals treated with 2.0, 5.0 and 10.0 mL/kg of flavouring died before the seventh day of treatment. The amounts of 0.5 and 1.0 mL/kg of the three additives were cytotoxic to erythrocytes, and treatment with the grape flavouring significantly induced the formation of micronucleated cells in the bone marrow of animals. Therefore, under the study conditions, the grape, plum and orange flavouring additives promoted significant toxicity to cells of the test systems used.

Montelukast sodium is a leukotriene antagonist of growing interest as an alternative therapy for asthma across different age groups due to its bronchoprotective, anti-inflammatory and anti-allergic properties. Currently, montelukast is commercialized only in oral solid dosage forms, which are the favorite of adult patients but may pose challenges in administration to children of young age or patients suffering from dysphagia. This review presents a comprehensive revision of scientific reports and patents on emerging strategies for the delivery of montelukast. A common ground to these reports is the pursue of an enhanced montelukast performance, by increasing its bioavailability and physico-chemical stability. A wide variety of strategies can be found, from the formation of supramolecular adducts with cyclodextrins to encapsulation in nanoparticles and liposomes. The new dosage forms for montelukast are designed for non-enteric absorption, some for absorption in the oral cavity and another two being for local action in the nasal mucosa or in the pulmonary epithelium. The review describes the emerging delivery strategies to circumvent the current limitations to the use of montelukast that are expected to ultimately lead to the development of more patient-compliant dosage forms.

Objective: To analyse the subtalar eversion range of motion during walking in women with fibromyalgia., Method: Twenty women diagnosed with fibromyalgia were directed to walk barefoot at comfortable and self-paced speed on a 7m walkway. Subtalar eversion range of motion was measured using the difference between the maximum and minimum values of subtalar eversion in stance phase. A range of motion between 4°-6° was considered as reference values for subtalar eversion during gait. Descriptive statistics were performed., Results: In both right and left lower limb analysis of subtalar eversion range of motion, five women showed joint hypomobility, and twelve showed hypermobility. Only one patient performed unaltered subtalar eversion range of motion in both lower limbs. Both joints expressed high variability, and there were no significant differences between the right and left sides., Conclusions: The findings suggest that biomechanical function of the subtalar joint eversion during the loading response phase of gait in women with fibromyalgia, by excessive rigidity or complacency joint, tends to be impaired. This finding suggests that the indication of walking as an auxiliary strategy in the treatment of women with fibromyalgia should be preceded by thorough examination of the mechanical conditions of the subtalar joint of the patient., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Adult neural stem cells (aNSCs) in zebrafish produce mature neurons throughout their entire life span in both the intact and regenerating brain. An understanding of the behavior of aNSCs in their intact niche and during regeneration in vivo should facilitate the identification of the molecular mechanisms controlling regeneration-specific cellular events. A greater understanding of the process in regeneration-competent species may enable regeneration to be achieved in regeneration-incompetent species, including humans. Here we describe a protocol for labeling and repetitive imaging of aNSCs in vivo. We label single aNSCs, allowing nonambiguous re-identification of single cells in repetitive imaging sessions using electroporation of a red-reporter plasmid in Tg(gfap:GFP)mi2001 transgenic fish expressing GFP in aNSCs. We image using two-photon microscopy through the thinned skull of anesthetized and immobilized fish. Our protocol allows imaging every 2 d for a period of up to 1 month. This methodology allowed the visualization of aNSC behavior in vivo in their natural niche, in contrast to previously available technologies, which rely on the imaging of either dissociated cells or tissue slices. We used this protocol to follow the mode of aNSC division, fate changes and cell death in both the intact and injured zebrafish telencephalon. This experimental setup can be widely used, with minimal prior experience, to assess key factors for processes that modulate aNSC behavior. A typical experiment with data analysis takes up to 1.5 months.

Adult Neural Stem Cells (aNSCs) generate new neurons that integrate into the pre-existing networks in specific locations of the Vertebrate brain. Moreover, aNSCs contribute with new neurons to brain regeneration in some non-mammalian Vertebrates. The similarities and the differences in the cellular and molecular processes governing neurogenesis in the intact and regenerating brain are still to be assessed. Toward this end, we recently established a protocol for non-invasive imaging of aNSC behavior in their niche in vivo in the adult intact and regenerating zebrafish telencephalon. We observed different modes of aNSC division in the intact brain and a novel mode of neurogenesis by direct conversion, which contributes to stem cell depletion with age. After injury, the generation of neurons is increased both by the activation of additional aNSCs and a shift in the division mode of aNSCs, thereby contributing to the successful neuronal regeneration. The cellular behavior we observed opens new questions regarding long-term aNSC maintenance in homeostasis and in regeneration. In this commentary we discuss our data and new questions arising in the context of aNSC behavior, not only in zebrafish but also in other species, including mammals.

Purpose: The glutathione family (GST) genes appear to play a role in the genesis of endometriosis. This case-control study aimed to compare the frequencies of GSTM1 and GSTT1 polymorphisms in women with endometriosis and women without endometriosis., Methods: Polymerase chain reaction was performed to analyze the GSTM1 and GSTT1 genotypes among women with surgically and histologically confirmed endometriosis (case group n = 121) and in women without evidence of endometriosis confirmed by laparoscopy for investigation the infertility or for laparoscopic tubal sterilization (control group n = 97)., Result(s): No differences in the frequencies of GSTM1 polymorphism (null genotype) were observed between the cases and controls: odds ratio (OR) = 1.13; 95 % CI 0.656-1.93 (p = 0.659). The GSTT1 polymorphism (null genotype) was more prevalent in the endometriosis group than in the control group (OR = 0.53; 95 % CI 0.94-0.29 (p = 0.039). No relationship between menstrual cycle interval and GSTM1 null genotype frequency was observed in either cases or controls (p = 0.370 and p = 0.664, respectively). In addition, no relationship between menstrual cycle interval and GSTT1 null genotype was observed in cases (p = 0.797) or controls (p = 0.052)., Conclusions: GSTM1 null genotype frequency was similar between cases and controls. The GSTT1 null genotype was more frequent in the control group.

High-performance liquid chromatography (HPLC) coupled to a diode-array detector (DAD) and electrospray ionization mass spectrometry (MS) was applied for the separation and identification of phenolic compounds in the n-hexane, ethyl acetate and methanol crude extract of Barbacenia blanchetii. The MS, MSn and UV data together with chemosystematic evidence allowed the structural characterization of five compounds: tricin, chrysoeriol, epi-gallocatechin, kaempferol 3-O-glucoside and caffeoylquinic acid. At the same time, these extracts were evaluated against butyrylcholinesterase using Ellman's method. All extracts inhibited BuChE in a concentration-dependent form; however, the methanol extract showed a better effect that the other extracts. These compounds have been identified previously in the Velloziaceae family, but for the first time as constituents of B. blanchetii.

Adult neural stem cells are the source for restoring injured brain tissue. We used repetitive imaging to follow single stem cells in the intact and injured adult zebrafish telencephalon in vivo and found that neurons are generated by both direct conversions of stem cells into postmitotic neurons and via intermediate progenitors amplifying the neuronal output. We observed an imbalance of direct conversion consuming the stem cells and asymmetric and symmetric self-renewing divisions, leading to depletion of stem cells over time. After brain injury, neuronal progenitors are recruited to the injury site. These progenitors are generated by symmetric divisions that deplete the pool of stem cells, a mode of neurogenesis absent in the intact telencephalon. Our analysis revealed changes in the behavior of stem cells underlying generation of additional neurons during regeneration., (Copyright © 2015, American Association for the Advancement of Science.)

Aim: To compare the corticosteroidogenic enzyme activities between normal cycling non-polycystic ovary syndrome (PCOS), and normoandrogenic PCOS (NA-PCOS) and hyperandrogenic PCOS (HA-PCOS) patients., Methods: This cohort study was conducted at Julio Muller University Hospital and Tropical Institute of Reproductive Medicine and Menopause, and enrolled 114 non-PCOS women and 355 PCOS patients. The steroidogenic enzyme activities were measured using the serum steroid product/precursor molar ratio., Results: In the Δ5 pathway the 17,20 lyase activity was equally low in the NA-PCOS and HA-PCOS women compared with the non-PCOS women (P < 0.01 and P < 0.001, respectively). In the Δ4 pathway, the 17,20 lyase activity was higher only in the HA-PCOS group (P < 0.001). The 17-hydroxylase activity was the same in PCOS and non-PCOS subjects (P > 0.05). The 3β-hydroxysteroid dehydrogenase II (3β-HSDII) activity was higher in the conversion of dehydroepiandrosterone into androstenedione in the HA-PCOS than in the NA-PCOS (P < 0.05) and the non-PCOS patients (P < 0.01). The aromatase activity was lower in the HA-PCOS than in the NA-PCOS (P < 0.05) patients and non-PCOS subjects (P < 0.01). In HA-PCOS subjects, the 17,20 lyase activity was related to insulin, estradiol, total testosterone concentrations and free androgen index in the Δ5 pathway. 3β-HSDII showed weak correlation with estradiol in the HA-PCOS group. Anthropometric parameters had little impact, if any, on the steroidogenic enzyme activities., Conclusion: The NA-PCOS and HA-PCOS patients demonstrated different enzyme activities, and the results provided new directions for future studies including PCOS patients with different phenotypes., (© 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.)

Purpose: To study the anti-inflammatory actions of electroacupuncture (EAc) on an experimental colitis model in mice., Methods: Thirty-eight male Swiss mice, divided in five groups, were subjected to induction of colitis by TNBS in 50% ethanol. Saline (SAL) and ethanol (ETNL) groups served as controls. TNBS+EAc and TNBS+ dexamethasone subgroups were treated with EAc 100Hz and dexamethasone (DEXA) 1 mg/Kg/day, respectively. After three days, a colon segment was obtained for quantification of myeloperoxidase (MPO) activity, immunohistochemistry for iNOS, malondialdehyde (MDA) and cytokines (IL-1β and IL-10)., Results: Neutrophilic activity, assayed as MPO activity, was significantly higher in the TNBS colitis group than that in the saline control group. TNBS+EAc group showed suppression of IL-10 in the colon. EAc treatment significantly reduced the concentration of MDA and the expression of iNOS, as compared to the other groups., Conclusion: Electroacupuncture 100Hz applied to acupoint ST-36 promotes an anti-inflammatory action on the TNBS-induced colitis, mediated by increase of IL-10 and decrease of iNOS expression.

Background: In non-PCOS patients the concentration of glycated hemoglobin (HbA1C) has been employed to identify individuals at higher risk for impaired glucose tolerance (IGT) and diabetes mellitus. A few studies have examined the role of HbA1C in PCOS patients and current results are controversial., Aim: To compare the strength of the association between glycated hemoglobin and other predictors of cardiovascular risk in polycystic ovary syndrome (PCOS)., Methods: This cross-sectional study enrolled 197 PCOS patients and 72 non-PCOS women. Transvaginal ultrasound, biochemical and hormone measurement were performed. Glycated hemoglobin (HbA1C) was correlated with other variables related to dysmetabolic/vascular diseases., Results: The HbA1C levels were 6.0±1.4% and 4.9±0.4% in PCOS patients and non-PCOS controls, respectively (p<0.001). The HbA1C levels were≥5.7% in 46.4% of PCOS and in none of the control subjects (OR=90.8). HbA1C was well-correlated with several anthropometric, metabolic and endocrine parameters. Stepwise multiple regression including HbA1C and other known predictors of cardiovascular risk resulted in a significant model in which body mass index (BMI) and free testosterone exhibited the best correlation with HbA1C (adjusted R(2)=0.530; F=39.8; p<0.001)., Conclusion: HbA1C was elevated and correlated with anthropometric, biochemical and endocrine variables of metabolic/vascular disease risks in PCOS patients. Combined HbA1C, BMI and free testosterone levels provided a significant model with potential use to evaluate metabolic/vascular disease in PCOS patients., (© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To determine the prevalence of chromosomal abnormalities and microdeletions on Y chromosome in infertile patients with oligozoospermia or azoospermia in Mato Grosso state, Brazil., Methods: This cross-sectional study enrolled 94 men from infertile couples. Karyotype analysis was performed by lymphocyte culture technique. DNA from each sample was extracted using non-enzymatic method. Microdeletions were investigated by polymerase chain reaction (PCR)., Results: With the use of cytogenetic analysis, five patients (5.3%) had abnormal karyotype, one azoospermic patient (1.1%) had karyotype 46,XY,t(7;1) (qter-p35), one (1.1%) with mild oligozoospermia had karyotype 46,XY,delY(q), and two other azoospermic patients had karyotype 47,XXY, consistent with Klinefelter syndrome (KS). One of them (1.1%) with severe oligozoospermia had karyotype 46,XY,8p+. Microdeletion on Y chromosome was found in the azoospermia factor c (AZFc) region in only one azoospermic patient (1.1%)., Conclusions: The prevalence of genetic abnormalities in oligo/azoospermic Brazilian men from infertile couple was 5.3%, and microdeletion on Y chromosome was not a common finding in this population (1.1%).

Background: To determine the prevalence of elevated glycated hemoglobin (HbA1c) and to examine its relationship with other carbohydrate metabolic parameter among Brazilian women with polycystic ovary syndrome (PCOS)., Methods: A cross-sectional study including 288 PCOS patients was conducted. Anthropometrical, clinical, biochemical and endocrine parameters were evaluated., Results: The mean age was 26.92 ± 5.51 years. HbA1c mean concentration was 5.83±1.34%. In 38.54% of patients, HbA1c was ≥ 5.7%. HbA1c was positively correlated with body weight (r = 0.142, P = 0.017), body mass index (P = 0.000), waist:hip ratio (P = 0.000), fat mass (P = 0.000), conicity index (P = 0.000), triglyceride (P = 0.001), C-peptide (P = 0.000), total testosterone (P = 0.003), free testosterone (P = 0.000), free androgen index (P = 0.006) and fasting insulin (P = 0.025). Using the oral glucose tolerance test, HbA1c showed positive correlation with glucose concentrations at any point in time (P < 0.05)., Conclusions: HbA1c was elevated in nearly 40% of PCOS patients and it showed positive correlation with several anthropometric and metabolic factors and androgen levels. The current study provides further evidence that HbA1C is higher in PCOS patients and may have a potential role in the prediction of dysglycemic disease in these women.