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Seizures occur when there is a hyper-excitation of the outer layer of the brain, with subsequent excessive synchrony in a group of neurons. According to the World Health Organization (WHO), an estimated 50 million people are affected by this disease, a third of whom are resistant to the treatments available on the market. Caffeine (1,3,7-trimethylxanthine), which belongs to the purine alkaloid family, is the most widely consumed psychoactive drug in the world. It is ingested by people through drinks containing this substance, such as coffee, and as an adjuvant in analgesic therapy with non-steroidal antiflammatory drugs. The present study evaluated the electrocorticographic changes observed in the hippocampus of Wistar rats subjected to acute doses of caffeine (150 mg/kg i.p), which represents a toxic dose of caffeine corresponding to an estimated acute intake of more than 12 cups of coffee to record its convulsant activity. Our results showed, for the first time, that the administration of high doses of caffeine (150 mg/kg i.p.) in rats caused an increase in the spectral distribution of power in all frequency bands and suggested the appearance of periods of ictal and interictal peaks in the electrocorticogram (ECog). We have also shown that the anticonvulsants phenytoin, diazepam and phenobarbital have a satisfactory response when associated with caffeine., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Manganese (Mn 2+ ) is an abundant chemical element in the earth's crust and is present in soil, water, and industrial environments, including mining, welding, and battery manufacturing. Manganese (Mn) is an essential metal needed as a cofactor for many enzymes to maintain proper biological functions. Excessive exposure to Mn in high doses can result in a condition known as manganism, which results in disorders of the neurological, cardiac, and pulmonary systems. The aim of this study was to assess cardiac susceptibility to manganese intoxication in Colossoma macropomum subjected to a fixed concentration of 4 mg/mL for a period of up to 96 h. This study used 45 Tambaquis (30.38 ± 3.5 g) divided into five groups of 9 animals/treatment. The treated groups were exposed to the manganese concentration for a period of 24, 48, 72, and 96 h, after which the animals' ECGs were recorded, showing heart rate, R-R interval, P-Q interval, QRS complex duration and S-T interval. The results showed that cardiac activity decreased as the contact time increased, with an increase in the P-Q and S-T intervals. This indicates that the breakdown of circulatory homeostasis in these animals was caused by contact time with manganese.

The purpose of this study was to characterize the activity of essential oils from Nepeta Cataria (EON) at concentrations of 125 μ L  L-1, 150 μ L  L-1, 175 μ L  L-1, and 200 μ L  L-1 on the behavior of loss of the posture reflex and recovery of the posture reflex and electrocardiographic activity and recording of the opercular beat of Colossoma macropomum during immersion bathing for a period of 5 min, in order to obtain a window for safe use during anesthesia. The fish (23.38 ± 3.5 g) were assigned to the following experiments: experiment 1 (latency to loss and recovery of the posture reflex): (a) 125 μ L  L-1, (b) 150 μ L  L-1, (c) 175 μ L  L-1, and (d) 200 μ L  L-1 (n = 9) per group. Experiment 2 (electrocardiographic and heartbeat recordings): (a) control group; (b) vehicle control group (2 ml of alcohol per liter of water), (c) 125 μ L  L-1, (d) 150 μ L  L-1, (e) 175 μ L  L-1, and (f) 200 μ L  L-1 (n = 9), per group. All the concentrations used showed efficacy in inducing loss of the posture reflex and reversibility with recovery of the posture reflex, but the electrocardiographic recordings indicated morphographic changes such as bradycardia during induction and p wave apiculation during recovery at the highest concentrations tested. In this way, we suggest a safe use window for short-term anesthesia with EON in the concentration range of 125 to 150 μ L  L-1 for juvenile Colossoma macropomum., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: To describe the methodological challenges and strategies of a web survey on the working conditions and health among delivery workers., Methods: The study population consisted of Brazilian delivery workers operating in the national territory. Procedures include building solid and ongoing collaboration with worker representatives and conducting a four-month data collection from February to May 2022, sharing the link to the online questionnaire on social media such as social networks (Facebook, Instagram) and messaging apps (WhatsApp, Telegram)., Results: The recruitment of 41 leaders or influencers of delivery workers increased the dissemination of the study, some of whom participated in the consensual validation of the questionnaire; the production of content for social media for the dissemination of the questionnaire link on social networks and applications, and the in-person dissemination of the study at the delivery workers' meeting points during the workday played a fundamental role, totaling around 132 hours in 45 shifts. The strategies adopted for data collection with a hybrid approach to dissemination made it possible to carry out the web survey. After four months of the web survey, 564 delivery workers, 543 men and 18 women, responded to the online questionnaire., Conclusion: The web survey presented methodological strategies to overcome the challenge of reaching workers, including hybrid work, to increase the participation of workers, on whom epidemiological research is still scarce.

Nile tilapia, Oreochromis niloticus, is the most cultivated fish species in the world, due to its low cost, high growth rate, environmental adaptability, and resistance to disease and stress. Anesthetics for fish become necessary in management because they minimize mortality during transport and maintenance of ponds, one of the most used anesthetics is clove oil, which has eugenol as the major substance, representing 90-95 % of clove oil. The present study evaluates the effect of eugenol on cardiac activity in Oreochromis niloticus specimens and relates it to behavioral data to determine a concentration window for safe anesthesia. For the comportamental analysis, was used five treatments (50, 75, 100, 125, and 150 μL·L -1 ) were evaluated and for the eletrocardiographic test was used seven groups (Control, Vehicle, 50, 75, 100, 125, and 150 μL·L -1 ), n = 9/treatment, totaling 108 animals. Behavioral and electrocardiographic tests were performed on all treatments during induction and recovery. The results of the behavioral tests demonstrated the reversibility of the effects with recovery of the posture reflex, varying according to the concentration. The ECG results showed a slow recovery because, at concentrations above 100 μL·L -1 , there was no full reversibility of the cardiac effects in the observed experiment time, which could cause greater changes in the tilapia hemodynamics, which led us to identify a window for safe anesthesia. Eugenol is an effective anesthetic in Nile tilapia juveniles when used in concentrations ranging from 50 to 100 μL·L -1 , if there is a need for anesthetic deepening, doses above 100 μL·L -1 , however, the animals must be monitored due to hemodynamic changes., Competing Interests: Declaration of competing interest The authors declare no following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2024. Published by Elsevier Inc.)

The emergence and continued geographic expansion of arboviruses and the growing number of infected people have highlighted the need to develop and improve multiplex methods for rapid and specific detection of pathogens. Sequencing technologies are promising tools that can help in the laboratory diagnosis of conditions that share common symptoms, such as pathologies caused by emerging arboviruses. In this study, we integrated nanopore sequencing and the advantages of reverse transcription polymerase chain reaction (RT-PCR) to develop a multiplex RT-PCR protocol for the detection of Chikungunya virus (CHIKV) and several orthoflaviviruses (such as dengue ( Orthoflavivirus dengue ), Zika ( Orthoflavivirus zikaense ), yellow fever ( Orthoflavivirus flavi ), and West Nile ( Orthoflavivirus nilense ) viruses) in a single reaction, which provides data for sequence-based differentiation of arbovirus lineages.

BACKGROUND Learning to read and write depends on the effective functioning of various sensory systems, including the auditory system. Auditory information processing involves behavioral and electrophysiological processes. Electrophysiological procedures are used to investigate activity in the auditory pathway in response to sound stimuli, and the associated cortical activity in discrimination, integration, and attention. The study evaluated electrophysiological testing for an auditory processing disorder and reading performance in 54 school students aged between 8 and 12 years. MATERIAL AND METHODS The study involved 54 public school students aged between 8 and 12 years, who were divided into a study group and control group. All children underwent basic audiological assessment, rating of reading and writing ability, non-verbal intelligence, auditory brainstem response, long-latency auditory-evoked potentials (LLAEP), frequency following responses (FFR), and auditory training (AT). RESULTS The basic audiological evaluation showed a statistically significant difference between groups only for the frequency of 6 kHz. The LLAEP response had a statistically significant difference between groups for N1 latency, P300 latency, and amplitude. Finally, there was a statistically significant difference between pre-AT and post-AT to LLAEP for latencies of P2, N2, and P300 and amplitudes of N2 and P300, and to FFR for latency of wave C. CONCLUSIONS This study showed that electrophysiological tests are sensitive tools for identifying deficits in the auditory pathway. Moreover, latency measures can detect improvements from an auditory training program. In this way, an auditory intervention program might help children with reading and writing difficulties.

Objectives: This study examined changes in magnetic resonance imaging (MRI) of temporomandibular joints (TMJ) with anterior displacement disk without reduction (DDwoR) and its correlation to clinical symptoms., Methods: 190 individuals with DDwoR were evaluated according to Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) and MRI. Pain's chronicity/intensity and limited mouth opening (locking) were correlated with: TMJ degeneration (MRI T1), effusion (T2), disc's shape and position (proton density)., Results: In 103 TMJ with DDwoR, hemiconvex shape (41.6%), sclerosis (45.6%) and mild effusion (47.6%) were the most prevalent findings. There was not association ( p  > .05) between: different DDwoR positions with pain's intensity/chronicity; effusion with locking. Disk deformation was associated with degeneration ( p  = .034) and pain's intensity ( p  = .006). Locking was associated with degeneration ( p  = .05)., Conclusions: Condylar osteodegeneration is often related to DDwoR. Locking by DDwoR is associated with severe levels of chronic pain and articular disk deformation.

COVID-19 changed and challenged education, with schools obliged to adapt to online settings. This study aims to evaluate the impact of a mental health curriculum implemented at schools, considering the implementation settings: online, onsite, and mixed (online and onsite). From kindergarten to high school, 933 students were evaluated by teachers regarding their social and emotional learning, strengths and difficulties, and academic outcomesin two measuring times: pre- and post-test. A qualitative analysis of teachers' adaptations to the online implementation was also conducted. Results revealed a positive impact with both mixed and onsite implementation. However, the mixed format demonstrated significant positive changes between the pre-and post-test, namely in relationship skills, responsible decision-making, internalized problems, and academic achievement. The mixed format with few online activities appears to have a more positive impact on students. Nevertheless, implementing social and emotional skills (SES) activities exclusively online seems to positively affect some SES domains more than onsite and mixed formats. Teachers used synchronous (e.g., digital platforms) and asynchronous (e.g., extra resources) adaptations for the implementation. This study shows that implementing mental health programs at schools, in this case, PROMEHS, is beneficial for students, even amidst the pandemic, and regardless of the implementation settings., Competing Interests: The authors declare no conflict of interest.

Antitumor property of Crotoxin (CTX), the major toxin from Crotalus durissus terrificus snake venom, has been demonstrated in experimental animal models and clinical trials. However, the direct action of this toxin on the significant events involved in neovascularization, which are essential for tumor growth and survival, has not been confirmed. This study investigated the effects of CTX on the key parameters of neovascularization in two- and three-dimensional culture models. Murine endothelial cell lines derived from thymus hemangioma (t.End.1) were treated at different concentrations of CTX (6.25-200 nM). Endothelial cell proliferation, cell adhesion, and actin cytoskeletal dynamics on laminin (10 µg/ml), type I collagen (10 µg/ml), and fibronectin (3 µg/ml) were evaluated along with the endothelial cell migration and formation of capillary-like tubes in 3D Matrigel. CTX concentration of 50 nM inhibited tube formation on 3D Matrigel and impaired cell adhesion, proliferation, and migration under both culture medium and tumor-conditioned medium. These actions were not accountable for the loss of cell viability. Inhibition of cell adhesion to different extracellular matrix components was related to the reduction of αv and α2 integrin distribution and cytoskeletal actin polymerization (F-actin), accompanied by inhibition of focal adhesion kinase (FAK), Rac1 (GTPase) signaling proteins, and actin-related protein 2/3 (Arp 2/3) complex. This study proved that CTX inhibits the major events involved in angiogenesis, particularly against tumor stimuli, highlighting the importance of the anti-angiogenic action of CTX in inhibition of tumor progression., 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 © 2021 Kato, Pimenta, Almeida, Zambelli, Santos and Sampaio.)

Objective: Little is known about the efficacy of products aiming to prevent radiodermatitis, which affects between 90-95% of women with breast cancer. The use of antioxidants is promising, however, there is a lack of evidenceon their effectiveness. Here, the authors present a clinical trial protocol to evaluate the effects of applying a cream containing nanoparticles with vitamin E to prevent radiodermatitis in patients with breast cancer., Method: The protocol recommends that 108 women with breast cancer, receiving radiotherapy, are included in this triple-blinded, randomized, controlled study at an oncology hospital. Patients will be divided in three groups of 36 individuals each: group A will receive a cream with lipid nanoparticles and vitamin E, group B will receive a cream without nanoparticles nor vitamin E, and group C will receive a cream with nanoparticles without vitamin E. The primary endpoints will evaluate the incidence, degree, and time of onset of radiodermatitis. The secondary endpoints will focus on the quality of life, symptoms, and local temperature. Patients will be assessed three times a week, from the start of their radiotherapy treatment to two weeks after the last session. This protocol was approved by the research ethics committee of the institutions involved and registered on an international trials database.

Objectives: Arthrocentesis is the simplest surgical intervention for the temporomandibular joint (TMJ). It can be performed on an outpatient basis at a low cost and with low morbidity. The objective is to release the articular disc by disrupting the adhesion formed between its surfaces and the mandibular fossa through hydraulic pressure generated by irrigation of the upper compartment of the TMJ. Viscosupplementation with hyaluronic acid during or after arthrocentesis improves clinical outcomes, increases mouth opening, and reduces pain levels. The aim of this study was to evaluate the efficiency of arthrocentesis plus hyaluronic acid viscosupplementation through clinical examination and preoperative magnetic resonance imaging in patients with unilateral disc displacement without reduction (DDwoR)., Methods: This analytical retrospective cross-sectional study clinically and radiologically evaluated 72 patients of both sexes with unilateral DDwoR. The following data were collected: sex, pain, age, duration of pain, maximum mouth opening, and patient pain perception on a visual analog scale. TMJ arthrocentesis was performed only once for each of the indicated joints. Data were collected before arthrocentesis (baseline) and at 7, 14, 30, 60, 90, and 180 days after the procedure (final evaluation)., Results: Between the baseline and final evaluation, there was a significant reduction in pain (p=0.001) and restoration of articular function. In addition, there was a significant increase in maximum mouth opening (p=0.001)., Conclusion: Patients with DDwoR undergoing arthrocentesis combined with hyaluronic acid injection showed significant improvement in the perceived pain and maximum mouth opening in the mid-term follow-up periods.

The necessity of incorporating a resilience-informed approach into urban planning and its decision-making is felt now more than any time previously, particularly in low and middle income countries. In order to achieve a successful transition to sustainable, resilient and cost-effective cities, there is a growing attention given to more effective integration of nature-based solutions, such as Sustainable Drainage Systems (SuDS), with other urban components. The experience of SuDS integration with urban planning, in developed cities, has proven to be an effective strategy with a wide range of advantages and lower costs. The effective design and implementation of SuDS requires a multi-objective approach by which all four pillars of SuDS design (i.e., water quality, water quantity, amenity and biodiversity) are considered in connection to other urban, social, and economic aspects and constraints. This study develops a resilience-driven multi-objective optimisation model aiming to provide a Pareto-front of optimised solutions for effective incorporation of SuDS into (peri)urban planning, applied to a case study in Brazil. This model adopts the SuDS's two pillars of water quality and water quantity as the optimisation objectives with its level of spatial distribution as decision variables. Also, an improved quality of life index (iQoL) is developed to re-evaluate the optimal engineering solutions to encompass the amenity and biodiversity pillars of SuDS. Rain barrels, green roofs, bio-retention tanks, vegetation grass swales and permeable pavements are the suitable SuDS options identified in this study. The findings show that the most resilient solutions are costly but this does not guarantee higher iQoL values. Bio-retention tanks and grass swales play effective roles in promotion of water quality resilience but this comes with considerable increase in costs. Permeable pavements and green roofs are effective strategies when flood resilience is a priority. Rain barrel is a preferred solution due to the dominance of residential areas in the study area and the lower cost of this option., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Here, we present a fully validated method using a hollow-fibre liquid-phase microextraction technique for the determination by gas chromatography-mass spectrometry (GC-MS) of amphetamine (AMP), methamphetamine (MET), fenproporex (FEN), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxyethylamphetamine (MDEA) in whole blood. The validation parameters presented successful values within those recommended by the Scientific Working Group for Forensic Toxicology (SWGTox) in the Standard Practices for Method Validation in Forensic Toxicology. The limits of detection ranged from 1 to 3 ng/mL, and the limits of quantification ranged from 2 to 5 ng/mL. The determination coefficients (r 2 ) ranged from 0.990 to 0.997, and the method presented good intraday and interday accuracy (from 90.4% to 97.2%) and satisfactory recovery (from 68% to 110%). No carryover was observed. The heteroscedasticity was tested, and only AMP presented homoscedasticity. Weighting factors were applied to correct the linearity of MET (1/x 2 ), MDA (1/x), FEN (1/x 1/2 ), MDMA (1/x 2 ) and MDEA (1/y). Dilution integrity was tested at ratios of 1:2, 1:5 and 1:10, and all maintained intraday precision (from 94.9% to 99.3%) and interday precision (from 89.4% to 94.9%). The validated method was applied to six real whole blood samples from individuals suspected of consuming ecstasy, and MDMA, MDA and amphetamine were successfully identified and quantified., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

3D printing technologies have been considered an important technology due to the ease manufacturing of objects, freedom of design, waste minimization, and fast prototyping. In chemistry, this technology potentializes the fabrication of conductive electrodes in large scale for sensing applications. Herein, we reported the modification of a 3D printed graphene electrode with Prussian blue. The modified electrode (3DGrE/PB) was characterized by microscopy (SEM and AFM) and spectroscopic techniques, and its electrochemical properties were compared to the traditional electrodes: glassy carbon, gold, and platinum. The 3DGrE/PB was used in the sensing of hydrogen peroxide in real-world samples of milk and mouthwash, and the results obtained according to the technique of batch-injection analysis were satisfactory for the concentration range typically found in such samples. Thus, 3DGrE/PB can be used as a new platform for sensing of molecular targets.

Raman spectroelectrochemistry is a powerful technique for characterizing structural changes of materials during electrochemical reactions and investigating the mechanism of film deposition and adsorption processes on the surfaces of electrodes. Moreover, in situ measurements enable identification of catalytic sites and reaction intermediates, which facilitates the comprehension of reaction mechanisms. The limitations of this technique include the high-cost and the complexity of the experimental arrangement required by commercial spectroelectrochemical cells (SEC). Thus, 3D-printing technology emerges as an excellent alternative for the production of SEC, with desirable shape, low-cost, and robustness in a short period of time. In this work, an SEC and a 3D-printed working electrode were fabricated from acrylonitrile-butadiene-styrene (ABS) and conductive graphene polylactic acid (PLA) filaments, respectively. The proposed SEC and the 3D-printed electrode were printed within 3.5 h with an estimated cost of materials of less than US $2. Then, the 3D-printed SEC and the electrode were used in a study of structural changes of Prussian blue according to different voltage bias.

Background: Several lines of evidence indicate that medical schools have been failing to adequately nurture empathy and the ethical dimension in their graduates, the lack of which may play a central role in the genesis of medical errors, itself a major source of avoidable deaths, incapacity and wasted resources. It has been widely proposed that medical schools should adopt evaluation strategies as a means to promote a culture of respectful relationships. However, it is not clear if evaluation strategies in medical schools have addressed key domains related to that aim, such as ethics, through the perspective of their students. Hence, we conducted a national survey of instruments used by Brazilian medical schools to assess clerkship rotations from the perspective of students, with a main focus on the ethical domain., Methods: The authors invited 121 randomly selected institutions to participate in the study. Key informants answered a questionnaire about clerkship rotations and sent copies of any instrument used to assess the quality of clerkship rotations according to the students' perspectives., Results: Twenty-six (53%) of 49 participating schools used an instrument to assess the quality of clerkship rotations according to the perspective of students. Just 13 (27%) schools had instruments containing at least one question encompassing the ethical domain. Only 2 (4%) schools asked students specifically about the occurrence of any negative experience concerning the ethical domain during rotations. Merely 1 (2%) school asked students about having witnessed patient mistreatment and none asked about mistreatment against students themselves., Conclusions: There are several missed opportunities in the way medical schools assess the quality of clerkship rotations regarding the ethical domain. Closing the gap between usual institutional discourses regarding ethics and how that dimension is assessed within clerkship rotations might represent an important step towards the improvement of medical education and healthcare systems., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Dry socket (DS) is one the most common and symptomatic post-extraction complications; however, no consensus on its treatment has been reached. This study aimed to develop a novel dressing material for DS containing the phenolic agent guaiacol and evaluate its biological properties., Methods: An inclusion complex of guaiacol and β-cyclodextrin (Gu/βcd) was prepared by freeze-drying. Its antibacterial activity over six oral bacteria was analyzed using the microdilution method, and its cytotoxicity in osteoblasts was assessed with the MTT assay. The alveolar healing process induced by Gu/βcd was evaluated histologically after the treatment of DS in rats., Results: βcd complexation potentiated Gu's antibacterial effect and reduced its cytotoxicity in osteoblasts. Bone trabeculae were formed in the alveolar apices of rats treated with Gu/βcd by day 7. On day 14, woven bone occupied the apical and middle thirds of the sockets; on day 21, the entire alveolus was filled by newly formed bone, which was in a more advanced stage of repair than the positive control (Alvogyl™)., Conclusion: The improvement in Gu's biological properties in vitro and the rapid alveolar repair in comparison with Alvogyl™ in vivo demonstrated the benefits of the Gu/βcd complex as a future alternative for the treatment of DS.

Rheumatoid arthritis is a common inflammatory disease that causes destruction of joints. Accurate recognition of active disease has significant implications in determining appropriate treatment; however, there is significant inter-rater variability in clinical joint assessment. This study aimed to assess the utility of thermographic imaging in the evaluation of inflammatory arthritis activity as an adjunct to clinical assessment. This was a cross-sectional study of 79 subjects recruited from the University of Alberta Outpatient Rheumatology clinic comparing the hand joints of 49 patients with rheumatoid arthritis (RA) diagnosed by American College of Rheumatology (ACR) criteria to 30 healthy volunteers. Convenience sampling of consecutive RA patients was undertaken. The effect of clinical assessment (HAQ and DAS-28) on joint temperature was evaluated using a linear mixed effect model. A thermography camera, FLIR T300 model, 30 Hz, was used to obtain both thermographic and digital images on subjects. Pearson's correlation coefficient was used to assess the correlation of clinical assessments and average joint temperature averaged over all joints. Thermographic analysis did not associate with clinical measures of disease activity. In RA patients, there was no statistically significant relationship between joint temperature and clinical assessment of disease activity including Health Assessment Questionnaire (coefficient estimate - 0.54, p = 0.056), swollen joints (coefficient estimate - 0.09, p = 0.238), or serologic markers of inflammation such as CRP (coefficient estimate - 0.006, p = 0.602) and ESR (coefficient estimate - 0.01, p = 0.503). Evaluation of disease activity requires a multifaceted approach that includes clinical assessment and appropriate imaging. There may be a role for thermography in assessment of larger joints; however, it does not appear to be an effective modality for the small joints of the hand.

In recent years, the functions of glial cells, namely, astrocytes and microglia, have gained prominence in several diseases of the central nervous system, especially in glioblastoma (GB), the most malignant primary brain tumor that leads to poor clinical outcomes. Studies showed that microglial cells or astrocytes play a critical role in promoting GB growth. Based on the recent findings, the complex network of the interaction between microglial/astrocytes cells and GB may constitute a potential therapeutic target to overcome tumor malignancy. In the present review, we summarize the most important mechanisms and functions of the molecular factors involved in the microglia or astrocytes-GB interactions, which is particularly the alterations that occur in the cell's extracellular matrix and the cytoskeleton. We overview the cytokines, chemokines, neurotrophic, morphogenic, metabolic factors, and non-coding RNAs actions crucial to these interactions. We have also discussed the most recent studies regarding the mechanisms of transportation and communication between microglial/astrocytes - GB cells, namely through the ABC transporters or by extracellular vesicles. Lastly, we highlight the therapeutic challenges and improvements regarding the crosstalk between these glial cells and GB.

Objective: To provide age-corrected and education-corrected norms for the Montreal Cognitive Assessment (MoCA) and the Memory Index Score (MoCA-MIS) in Brazil., Methods: Community-dwelling outpatients were enrolled if they had no history of neurologic or psychiatric diseases and were not taking any drugs with effects on the central nervous system. Dementia has been excluded with the Functional Activities Questionnaire. The final sample consisted of 597 cognitively healthy Brazilians aged 50 to 90 years. To account for nonlinear relationships, we have used fractional polynomials that provide a flexible parameterization for continuous variables., Results: According to the original proposed cutoff (≤25 points), 87% of our sample would be considered impaired. Even using a more conservative suggestion (≤22 points), 67% of our normative sample would be regarded as impaired. These data reinforce the need of adjusting cutoffs for schooling in populations with heterogeneous educational backgrounds. MoCA scores presented a nonlinear positive association with education tending to a plateau at higher levels (P < 0.001). On the other hand, MoCA-MIS scores presented a nonlinear negative relationship with age, with an accelerated pattern at higher age levels (P < 0.001)., Conclusions: We presented normative data for the MoCA and the MoCA-MIS that will facilitate the use of the test in Brazil and, potentially, in other populations with substantial proportions of low-educated individuals. Moreover, we described a systematic approach for adjusting the effects of age and education using fractional polynomials and provided suggestions on how to account for the nonlinear relationship that is frequently encountered between demographic factors and measures of cognitive performance., (Copyright © 2018 John Wiley & Sons, Ltd.)

The Gené's organ (GO) secretes a waxy substance on eggs that reduces water loss and has antimicrobial properties. The current study evaluated morphological and histochemical aspects of GO in Amblyomma sculptum from the period of post-feeding - when ticks detach from the host - to the stage just before oviposition. In this species, GO is composed of a corpus and two pairs of glands, namely, cranial and caudal. Glandular cells are joined laterally by a system of interdigitating membranes with junctional complexes. Histochemistry showed that lipid droplets became more evident as GO developed, while glycogen gradually disappeared, and proteins were detected only near the onset of oviposition. The ultrastructural results revealed a marked distension of the cuticle filled with an amorphous material. Glandular cells showed poor endoplasmatic reticulum, many mitochondria mainly in the basal cell poles and a very developed basal labyrinth. We concluded that the development of GO in A. sculptum ticks was continuous and progressive, and it started after detachment from the host. Additionally, the ultrastructure study suggests that gland cells have an important absorption ability and a low synthetic activity, which indicates that the majority of wax precursors are derived from haemolymph., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

The association between hypertension and frailty syndrome in older adults remains unclear. There is scarce information about the prevalence of hypertension among frail elderly patients or on its relationship with frailty. Up to one quarter of frail elderly patients present without comorbidity or disability, yet frailty is a leading cause of death. The knowledge and better control of frailty risk factors could influence prognosis. The present study evaluated: (1) the prevalence of hypertension in robust, prefrail, and frail elderly; and (2) factors that might be associated with frailty including hypertension. A cross-sectional study was conducted in 619 older adults at a university-based outpatient center. Study protocol included sociodemographic data, measures of blood pressure and body mass index, frailty screening according to the internationally validated FRAIL (fatigue, resistance, ambulation, illnesses, and loss of weight) scale, number of comorbidities, drug use assessment, physical activity, cognitive status, and activities of daily living. Ordinal logistic regression was used to evaluate factors associated with frailty. Prevalence of hypertension and frailty was 67.3% and 14.8%, respectively, in the total sample. Hypertension was more prevalent in the prefrail (72.5%) and frail (83%) groups than among controls (51.7%). Hypertension, physical activity, number of prescribed drugs, and cognitive performance were significantly associated with frailty status. Hypertension presented an odds ratio of 1.77 towards frailty (95% confidence interval, 1.21-2.60; P = .002). Hypertension was more prevalent in frail elderly patients and was significantly associated with frailty. Intensive control of hypertension could influence the trajectory of frailty, and this hypothesis should be explored in future prospective clinical trials., (©2017 Wiley Periodicals, Inc.)

Traffic accidents are responsible for 1.25 million deaths worldwide and are the most common cause of death among those aged 15-29 years. In Brazil, traffic accidents caused more than 44,000 deaths in 2014. The use of psychoactive drugs is an important risk factor for being involved in traffic accidents. Previous studies have found that psychoactive substances are commonly used by truck drivers in Brazil to maintain their extensive work schedule and stay awake while driving during nighttime hours. The state of Sao Paulo is one of the most important states regarding goods transportation. Important highways cross through Sao Paulo to other regions from Brazil and to other countries in Latin America. This study aims to determine the prevalence of illicit drug use by truck drivers in the state of Sao Paulo through toxicological analyses of oral fluid. Truck drivers were randomly stopped by police officers on federal roads during morning hours. Oral fluid samples were collected using the Quantisal™ device. In addition, a questionnaire concerning sociodemographic characteristics and health information was administered. Oral fluid samples were screened for amphetamine, cocaine, and tetrahydrocannabinol (Δ9-THC) by ELISA and the confirmation was performed using ultra performance liquid chromatography with tandem mass spectrometry detection (UPLC-MS/MS). Of the 764 drivers stopped, 762 agreed to participate. The participants were driving an average of 614km and 9.4h a day. Of the total samples, 5.2% (n=40) tested positive for drugs. Cocaine was the most frequently found drug (n=21), followed by amphetamine (n=16) and Δ9-THC (n=8). All drivers were men with an average age of 42.5 years. With these results we were able to verify that many truck drivers were still consuming psychoactive drugs while driving, and cocaine was the most prevalent one. This reinforces the need for preventive measures aimed at controlling the use of illicit drugs by truck drivers in Brazil., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Type 2 diabetes mellitus currently ranks high among indicators used in Global Burden of Disease Studies. The current study estimated the burden of disease attributable to type 2 diabetes mellitus and its chronic complications in Brazil, 2008. We calculated disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) stratified by gender, age bracket, and major geographic region. Type 2 diabetes mellitus accounted for 5% of the burden of disease in Brazil, ranking 3rd in women and 6th in men in the composition of DALYs. The largest share of DALYs was concentrated in the 30-59-year age bracket and consisted mainly of YLDs. The highest YLL and YLD rates were in the Northeast and South of Brazil, respectively. Chronic complications represented 80% of YLDs from type 2 diabetes mellitus. Type 2 diabetes mellitus ranked as a leading health problem in Brazil in 2008, accounting for relevant shares of mortality and morbidity.

An optical fiber specklegram sensor interrogation method based on speckle pattern fragmentation is presented. The acquired specklegram images are divided in a square grid, creating sub-images that are further processed by a correlation technique, allowing the quantification of localized changes in the specklegrams. The methodology was tested on the assessment of linear displacements using a microbending transducer, by evaluating different grid sizes. For a 5×5 grid, a 2.53  mm -1 sensitivity over a 0.27 mm range was obtained, representing an extension of 237.5% in comparison to the standard interrogation technique. Therefore, the presented technique allows enhancing the sensor dynamic range without modifying the experimental setup.

Nanotechnology has provided powerful tools to improve the chemotherapy of cancer. Different nanostructures have been developed which deliver the anticancer drugs more selectively to tumor than to healthy tissues. The result has generally been the increase in efficacy and safety of classical anticancer drugs. In recent years, several studies have focused not only on the delivery of anticancer drugs to tumors, but also on delivering the drugs to specific organelles of cancer cells. Endoplasmic reticulum, Golgi apparatus, lysosomes, mitochondria, and nucleus have been the targets of different nanostructured drug delivery systems developed with the goal of circumventing drugresistance, increasing drug efficacy, and so on. So far, the results described in the literature show that this strategy may be used to improve chemotherapy outcomes. In this review a discussion is presented on the strategies described in the literature to deliver anticancer drugs to specific organelles of cancer cells by using nanostructures.

Introduction: Impaired wound healing has been widely reported in diabetes. Linoleic acid (LA) accelerates the skin wound healing process in non-diabetic rats. However, LA has not been tested in diabetic animals., Objectives: We investigated whether oral administration of pure LA improves wound healing in streptozotocin-induced diabetic rats., Methods: Dorsal wounds were induced in streptozotocin-induced type-1 diabetic rats treated or not with LA (0.22 g/kg b.w.) for 10 days. Wound closure was daily assessed for two weeks. Wound tissues were collected at specific time-points and used to measure fatty acid composition, and contents of cytokines, growth factors and eicosanoids. Histological and qPCR analyses were employed to examine the dynamics of cell migration during the healing process., Results: LA reduced the wound area 14 days after wound induction. LA also increased the concentrations of cytokine-induced neutrophil chemotaxis (CINC-2αβ), tumor necrosis factor-α (TNF-α) and leukotriene B4 (LTB4), and reduced the expression of macrophage chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1). These results together with the histological analysis, which showed accumulation of leukocytes in the wound early in the healing process, indicate that LA brought forward the inflammatory phase and improved wound healing in diabetic rats. Angiogenesis was induced by LA through elevation in tissue content of key mediators of this process: vascular-endothelial growth factor (VEGF) and angiopoietin-2 (ANGPT-2)., Conclusions: Oral administration of LA hastened wound closure in diabetic rats by improving the inflammatory phase and angiogenesis., Competing Interests: The authors have declared that no competing interests exist.

Objective: To propose a novel ultrasound scoring system for hand and wrist joints (US10) for evaluation of patients with early rheumatoid arthritis (RA) and to correlate the US10 with clinical, laboratory and functional variables., Methods: Forty-eight early RA patients underwent clinical and laboratory evaluations as well as blinded ultrasound (US) examinations at baseline, three, six and 12 months. The proposed US10 system involved the assessment of the wrist, second and third metacarpophalangeal and proximal interphalangeal joints. The score consisted of inflammation parameters (synovial proliferation [SP], power Doppler [PD] and tenosynovitis [TN]) and joint damage parameters (bone erosion [BE] and cartilage damage [CD]). SP, PD, BE and CD were scored qualitatively (0-1) and semi-quantitatively (grades 0-3). Tenosynovitis was scored as presence/absence. The evaluation also involved the 28-Joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ) and C-reactive protein level (CRP)., Results: Mean duration of symptoms was 7.58±3.59 months. Significant correlations (p<0.05) were found between inflammation parameters and CRP at baseline and between the changes in these variables throughout the study. Significant correlations (p<0.05) were found between DAS28 score and both PD and TN at baseline and between the changes in DAS28 score and both SP and TN throughout the follow up. Moreover, significant correlations were found between the changes in inflammation parameter scores and HAQ score throughout the follow up., Conclusion: The proposed US10 scoring system proved to be a useful tool for monitoring inflammation and joint damage in early RA patients, demonstrating significant correlations with longitudinal changes in disease activity and functional status., (Copyright © 2016 Elsevier Editora Ltda. All rights reserved.)

In forensic bioanalytical methods, there is a general agreement that calibrators should be prepared by fortifying analytes in matrix-based blank samples (matrix-based). However, in the case of vitreous humor (VH), the collection of blank samples for the validation and for routine analysis would require the availability of many cadavers. Besides the difficulty of obtaining enough blank VH, this procedure could also represent an ethical issue. Here, a study of matrix effect was performed taking into consideration human and bovine vitreous and saline solution (SS) (NaCl 0.9%). Tricyclic antidepressants [amitriptyline (AMI), nortriptyline (NTR), imipramine (IMI) and desipramine (DES)] were used as model analytes and were extracted from samples by means of liquid-phase microextraction and detected by gas chromatography-mass spectrometry. Samples of human and bovine VH and SS were prepared in six different concentrations of antidepressants (5, 40, 80, 120, 160 and 200 ng/mL) and were analyzed. Relative matrix effect was evaluated by applying a two-tailed homoscedastic Student's t-test, comparing the results obtained with the set of data obtained with human VH and bovine VH and SS. No significant matrix effect was found for AMI and NTR in the three evaluated matrices. However, a great variability was observed for IMI and DES for all matrices. Once compatibilities among the matrices were demonstrated, the method was fully validated for AMI and NTR in SS. The method was applied to six VH samples deriving from real cases whose femoral whole blood (FWB) was analyzed by a previously published method. An average ratio (VH/FWB) of ∼ 0.1 was found for both compounds., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

This study evaluated the flexion-relaxation phenomenon (FRP) and flexion-relaxation ratios (FR-ratios) using surface electromyography (sEMG) of the cervical extensor muscles of computer workers with and without chronic neck pain, as well as of healthy subjects who were not computer users. This study comprised 60 subjects 20-45years of age, of which 20 were computer workers with chronic neck pain (CPG), 20 were computer workers without neck pain (NPG), and 20 were control individuals who do not use computers for work and use them less than 4h/day for other purposes (CG). FRP and FR-ratios were analyzed using sEMG of the cervical extensors. Analysis of FR-ratios showed smaller values in the semispinalis capitis muscles of the two groups of workers compared to the control group. The reference FR-ratio (flexion relaxation ratio [FRR], defined as the maximum activity in 1s of the re-extension/full flexion sEMG activity) was significantly higher in the computer workers with neck pain compared to the CG (CPG: 3.10, 95% confidence interval [CI95%] 2.50-3.70; NPG: 2.33, CI95% 1.93-2.74; CG: 1.99, CI95% 1.81-2.17; p<0.001). The FR-ratios and FRR of sEMG in this study suggested that computer use could increase recruitment of the semispinalis capitis during neck extension (concentric and eccentric phases), which could explain our results. These results also suggest that the FR-ratios of the semispinalis may be a potential functional predictive neuromuscular marker of asymptomatic neck musculoskeletal disorders since even asymptomatic computer workers showed altered values. On the other hand, the FRR values of the semispinalis capitis demonstrated a good discriminative ability to detect neck pain, and such results suggested that each FR-ratio could have a different application., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The World Health Organization Essential Medicines List (WHO-LIST) and national essential medicines lists differ because many countries face significant challenges, such as product availability, cost, product quality and epidemiological disease profiles. In Brazil, governments pay for drugs that are included on the federal, state and municipal government (REMUME) lists. The extent to which municipal lists differ from state and national lists and from the WHO-LIST is unclear. We investigate the use of the WHO-LISTas a tool with which to evaluate the selection process for the essential psychiatric medicines in the public system coverage list of Brazilian communities (cities) and the use of the target drugs., Methods: Municipal health secretaries were interviewed regarding the selection process for REMUMEs and the antidepressants and benzodiazepines included in REMUMEs and reference lists. We calculated the use of REMUME drugs that appeared or did not appear on reference lists according to the defined daily dose (DDD) per 10,000 inhabitants., Results: Local physicians and pharmacists without specific training or explicit criteria developed the REMUMEs. Of the 13 drugs and 24 products (i.e., the different dosages of these 13 drugs) in the REMUMEs, 8 drugs and 10 products were included in at least one reference list and in one municipal list; 4 drugs and 6 products were included in at least one reference list but in none of the municipal lists; and 7 drugs and 8 products were included in at least one municipal list but in none of the reference lists. The antidepressants that appeared in at least one municipal list but in none of the reference lists represented 25.1 % (mean 60.9 DDD/10,000 inhabitants-day) of the usage. The benzodiazepines that appeared in at least one of the municipal lists but in none of the reference lists represented 14.7 % mean 18.5 DDD/10,000 inhabitants-day) of the usage., Conclusions: Brazilian cities have no rigorous processes for selecting the drugs that appear on their lists, and drugs that do not appear on the reference lists represent a significant proportion of antidepressant and benzodiazepine use, resulting in public health and social problems.

The advanced glycation end products (AGEs) of proteins are common factors in the pathophysiology of a number of disorders related to aging. The skin generation of AGEs occurs mainly through nonenzymatic glycation reactions of extracellular matrix (ECM) proteins in the dermis. The AGEs have been touted as one of the factors responsible for healing impairment and loss of elasticity of healing skin, affecting growth, differentiation, and cellular motility, as well as cytokines response, metalloproteinases expression, and vascular hemostasis. In this study, we generated an in vitro full-thickness reconstructed skin based on a glycated collagen matrix dermal compartment to evaluate the effects of glycation on dermal ECM and ultimately on the epidermis. Epidermal differentiation and stratification patterns and the glycation-induced ECM changes were evaluated by histology, immunohistochemistry, and mRNA levels. In this study, we reported for the first time that changes in the dermal matrix caused by collagen I in vitro glycation processes also affect the epidermal compartment. We demonstrated that glycation of collagen induces expression of carboxymethyllysine in dermal and epidermal compartments and, consequently, an aging phenotype consisting of poor stratification of epidermal layers and vacuolization of keratinocyte cytoplasm. Increased expression of cell-cell adhesion markers, such as desmoglein and E-cadherin in glycated skins, is observed in the stratum spinosum, as well as an increased compression of dermal collagen matrix. We also submitted our 3D model of reconstructed glycated skin to screening of anti-AGE molecules, such as aminoguanidine, which prevented the glycated morphological status. Controlled human studies investigating the effects of anti-AGE strategies against skin aging are largely missing. In this context, we proposed the use of skin equivalents as an efficient model to investigate cellular interactions and ECM changes in the aging skin, and to elucidate the role of anti-AGEs molecules in this process.

Obesity is a highly heritable but genetically heterogeneous disorder. Various well-known microdeletion syndromes (e.g. 1p36, 2q37, 6q16, 9q34, 17p11.2) can cause this phenotype along with intellectual disability (ID) and other findings. Chromosomal microarrays have identified 'new' microdeletion/duplication syndromes often associated with obesity. We report on 2 unrelated patients with an overlapping region of deletion at 1p21.3p21.2, and a third patient with a de novo recurrent unbalanced translocation der(8)t(8;12)(p23.1;p13.31), detected by 180K array CGH in a prospective cohort of syndromic obesity patients. Deletion of 1p21.3 is a rare condition, and there have been only 11 cases of the same recurrent translocation between chromosomes 8 and 12 [t(8;12)] reported to date. The former has been associated with ID, autistic spectrum disorder (ASD) and mild dysmorphic features, and in 4 patients who were obese or had a tendency to obesity, a minimal overlapping region of 2 genes, DPYD and MIR137, was detected; t(8;12) has recently been recognized to cause a childhood obesity syndrome due to duplication of the GNB3 gene. Thus, our findings add to the existing literature on the clinical description of these new syndromes, providing additional support that these loci are associated with syndromic obesity. We suggest that heterozygous loss of MIR137 may contribute to obesity as well as ID and ASD.

The control of the most important pest of stored maize, the weevil Sitophilus zeamais Motschulsky (Coleoptera: Curculionidae), is mainly achieved with the use of pyrethroid insecticides. However, the intensive use of these compounds has led to the selection of resistant populations and has compromised the control efficacy of this insect pest. Here, the toxicity of indoxacarb for a potential use in the control of S. zeamais was assessed on 13 Brazilian populations. Concentration-mortality bioassays, in the presence of synergists (piperonyl butoxide, triphenyl phosphate, and diethyl maleate), were used to assess potential metabolic-based indoxacarb resistance mechanisms. We also assessed the behavioral (locomotory) responses of these populations to indoxacarb exposure. The results showed significant differences between the populations (LD50 values ranged from 0.06 to 13.99 mg a.i/kg of grains), resulting in resistance ratios of >200-fold between the least (Canarana-MT) and the most (Espirito Santo do Pinhal-SP) susceptible populations. The results obtained with synergized indoxacarb suggest the involvement of esterases and glutathione-S-transferases on indoxacarb action, and also suggest the involvement of cytochrome P450-dependent monooxygenases as a potential indoxacarb resistance mechanism in Brazilian populations of S. zeamais. Although indoxacarb-induced behavioral avoidance varied among populations, some resistant populations (e.g., Canarana-MT) were able to reduce exposure to indoxacarb by spending more time in the nontreated areas. Collectively, our findings indicate that the behavioral (locomotory) and physiological responses of these insects may compromise the control efficacy of oxadiazine insecticides (e.g., indoxacarb) in Brazilian populations of S. zeamais., (© The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Compare the effectiveness of ultrasound and fluoroscopy to guide intra-articular injections (IAI) in selected cases., Material and Methods: A prospective study in our outpatient clinics at the Rheumatology Division at Universidade Federal de São Paulo (UNIFESP), Brazil, was conducted to compare the short-term (4 weeks) effectiveness of ultrasound and fluoroscopy-guided IAI in patients with rheumatic diseases. Inclusion criteria were: adults with refractory synovitis undergoing IAI with glucocorticoid. All patients had IAI performed with triamcinolone hexacetonide (20mg/ml) with varying doses according to the joint injected., Results: A total of 71 rheumatic patients were evaluated (52 women, 44 whites). Mean age was 51.9 ± 13 years and 47 of them (66.2%) were on regular DMARD use. Analysis of the whole sample (71 patients) and hip sub-analysis (23 patients) showed that significant improvement was observed for both groups in terms of pain (P < 0.001). Global analysis also demonstrated better outcomes for patients in the FCG in terms of joint flexion (P < 0.001) and percentage change in joint flexion as compared to the USG. Likert scale score analyses demonstrated better results for the patients in the USG as compared to the FCG at the end of the study (P < 0.05). No statistically significant difference between groups was observed for any other study variable., Discussion and Conclusion: Imaging-guided IAI improves regional pain in patients with various types of synovitis in the short term. For the vast majority of variables, no significant difference in terms of effectiveness was observed between fluoroscopy and ultrasound guided IAI.

Objectives: The aim of the present study was to demonstrate the utility of ultrasound to show subclinical feet disease in RA., Methods: The foot joints (talocrural, talocalcaneal, talonavicular, naviculocuneiform, calcaneocuboid, 5th tarsometatarsal and 1st to 5th metatarsophalangeal [MTP] joints) of 50 healthy subjects and 50 RA patients, with asymptomatic feet, were compared bilaterally. Statistical significance was set at 5%., Results: Twenty-two joints were examined per individual (2200 in the entire sample). Significantly higher values were found in the RA group regarding quantitative synovitis in all joints recesses (p<0.003), the presence of synovitis (p<0.035) (except the 5thtarsometatarsal and 3rdMTP joint), power Doppler (PD) signals (p<0.029) (talocalcaneal, talonavicular, 1st, 2nd, 3rd and 4thMTP joints) and bone erosion (p<0.003) (except for the talocrural and talocalcaneal joints). Synovitis, PD signals and erosion were observed in 18.3% and 3.05% (p<0.001), 5.77% and 0.22% (p<0.001) and 34.45% and 2.85% (p<0.001) of the RA group and control group, respectively. Greater DAS-28, HAQ and FFI values were associated with ultrasound findings in only some joints (p<0.046). Interobserver agreement was ≤0.686 for semi-quantitative synovitis, ≤0.641 for quantitative synovitis, ≤0.474 for PD signals and ≤1.000 for erosion. Low Cohen Kappa values were found in the correlation between radiography and ultrasound (0.084-0.400). CONCLUSIONS. Ultrasound on RA asymptomatic feet demonstrated a significantly greater number of inflammatory changes in current activity (synovitis, PD signals) and sequelae (erosion) in comparison to control subjects. In the midfoot, the talonavicular joint has the greatest number of ultrasound findings.

The scope of this study was to evaluate the sleep/wake cycle in shift work nurses, as well as their sleep quality and chronotype. The sleep/wake cycle was evaluated by keeping a sleep diary for a total of 60 nurses with a mean age of 31.76 years. The Horne & Östberg Questionnaire (1976) for the chronotype and the Pittsburgh Sleep Quality Index (PSQI) for sleep quality were applied. The results revealed a predominance of indifferent chronotypes (65.0%), followed by moderately evening persons (18.3%), decidedly evening persons (8.3%), moderately morning persons (6.6%) and decidedly morning persons (1.8%). The sleep quality perception was analyzed by the visual analogical scale, showing a mean score of 5.85 points for nighttime sleep and 4.70 points for daytime sleep, which represented a statistically significant difference. The sleep/wake schedule was also statistically different when considering weekdays and weekends. The PSQI showed a mean of 7.0 points, characterizing poor sleep quality. The results showed poor sleep quality in shift work nurses, possibly due to the lack of sport and shift work habits.

The aim of this study was to investigate whether treatment with tributyrin (Tb; a butyrate prodrug) results in protection against diet-induced obesity and associated insulin resistance. C57BL/6 male mice fed a standard chow or high-fat diet were treated with Tb (2 g/kg body wt, 10 wk) and evaluated for glucose homeostasis, plasma lipid profile, and inflammatory status. Tb protected mice against obesity and obesity-associated insulin resistance and dyslipidemia without food consumption being affected. Tb attenuated the production of TNFα and IL-1β by peritoneal macrophages and their expression in adipose tissue. Furthermore, in the adipose tissue, Tb reduced the expression of MCP-1 and infiltration by leukocytes and restored the production of adiponectin. These effects were associated with a partial reversion of hepatic steatosis, reduction in liver and skeletal muscle content of phosphorylated JNK, and an improvement in muscle insulin-stimulated glucose uptake and Akt signaling. Although part of the beneficial effects of Tb are likely to be secondary to the reduction in body weight, we also found direct protective actions of butyrate reducing TNFα production after LPS injection and in vitro by LPS- or palmitic acid-stimulated macrophages and attenuating lipolysis in vitro and in vivo. The results, reported herein, suggest that Tb may be useful for the treatment and prevention of obesity-related metabolic disorders.

Background: Wound healing is impaired in diabetes mellitus, but the mechanisms involved in this process are virtually unknown. Proteins belonging to the insulin signaling pathway respond to insulin in the skin of rats., Objective: The purpose of this study was to investigate the regulation of the insulin signaling pathway in wound healing and skin repair of normal and diabetic rats, and, in parallel, the effect of a topical insulin cream on wound healing and on the activation of this pathway., Research Design and Methods: We investigated insulin signaling by immunoblotting during wound healing of control and diabetic animals with or without topical insulin. Diabetic patients with ulcers were randomized to receive topical insulin or placebo in a prospective, double-blind and placebo-controlled, randomized clinical trial (NCT 01295177) of wound healing., Results and Conclusions: Expression of IR, IRS-1, IRS-2, SHC, ERK, and AKT are increased in the tissue of healing wounds compared to intact skin, suggesting that the insulin signaling pathway may have an important role in this process. These pathways were attenuated in the wounded skin of diabetic rats, in parallel with an increase in the time of complete wound healing. Upon topical application of insulin cream, the wound healing time of diabetic animals was normalized, followed by a reversal of defective insulin signal transduction. In addition, the treatment also increased expression of other proteins, such as eNOS (also in bone marrow), VEGF, and SDF-1α in wounded skin. In diabetic patients, topical insulin cream markedly improved wound healing, representing an attractive and cost-free method for treating this devastating complication of diabetes., Trial Registration: ClinicalTrials.gov NCT01295177.

The effects of oral ingestion of oleic (OLA) and linoleic (LNA) acids on wound healing in rats were investigated. LNA increased the influx of inflammatory cells, the concentration of hydrogen peroxide (H(2)O(2)) and cytokine-induced neutrophil chemoattractant-2αβ (CINC-2αβ), and the activation of the transcription factor activator protein-1 (AP-1) in the wound at 1  hour post wounding. LNA decreased the number of inflammatory cells and IL-1, IL-6, and macrophage inflammatory protein-3 (MIP-3) concentrations, as well as NF-κB activation in the wound at 24  hours post wounding. LNA accelerated wound closure over a period of 7 days. OLA increased TNF-α concentration and NF-κB activation at 1  hour post wounding. A reduction of IL-1, IL-6, and MIP-3α concentrations, as well as NF-κB activation, was observed 24  hours post wounding in the OLA group. These data suggest that OLA and LNA accelerate the inflammatory phase of wound healing, but that they achieve this through different mechanisms.

The present study investigated the effects of chronic hyperprolinemia on oxidative and metabolic status in liver and serum of rats. Wistar rats received daily subcutaneous injections of proline from their 6th to 28th day of life. Twelve hours after the last injection the rats were sacrificed and liver and serum were collected. Results showed that hyperprolinemia induced a significant reduction in total antioxidant potential and thiobarbituric acid-reactive substances. The activities of the antioxidant enzymes catalase and superoxide dismutase were significantly increased after chronic proline administration, while glutathione (GSH) peroxidase activity, dichlorofluorescin oxidation, GSH, sulfhydryl, and carbonyl content remained unaltered. Histological analyses of the liver revealed that proline treatment induced changes of the hepatic microarchitecture and increased the number of inflammatory cells and the glycogen content. Biochemical determination also demonstrated an increase in glycogen concentration, as well as a higher synthesis of glycogen in liver of hyperprolinemic rats. Regarding to hepatic metabolism, it was observed an increase on glucose oxidation and a decrease on lipid synthesis from glucose. However, hepatic lipid content and serum glucose levels were not changed. Proline administration did not alter the aminotransferases activities and serum markers of hepatic injury. Our findings suggest that hyperprolinemia alters the liver homeostasis possibly by induction of a mild degree of oxidative stress and metabolic changes. The hepatic alterations caused by proline probably do not implicate in substantial hepatic tissue damage, but rather demonstrate a process of adaptation of this tissue to oxidative stress. However, the biological significance of these findings requires additional investigation., (Copyright © 2011 Wiley Periodicals, Inc.)

During theoretical and practical activities in clinical training areas, nursing teachers provide the bases needed for the development of future professionals. The goal is to understand the experience of nursing teachers with nursing students in clinical training areas. Therefore, a phenomenological qualitative method was chosen, and Martin Heidegger's philosophical framework was used to support data analysis. Five faculty from a Chilean university participated in the study. The analysis permitted discovering the following themes: being a faculty at the hospital, contact with nurse practitioners and being a faculty in care teaching. The study demonstrated that teaching/care integration is a constructive element that facilitates the teaching and learning process, aiming to prepare nursing professionals who incorporate the bases of authentic care into their activities.

The aim of the present study was to investigate the long-term effectiveness of and tolerance to Yttrium-90 and Samarium-153-particulate hydroxyapatite radiation synovectomy in patients with rheumatoid arthritis (RA) and chronic knee synovitis. Eight-four patients (90 knees) with chronic knee synovitis and RA (according to the American College of Rheumatology criteria) participated in a controlled, double-blinded trial. Patients were randomized to receive an intra-articular injection with either 5 mCi Yttrium-90 plus 40 mg of triamcinolone hexacetonide (Y/TH Group), 15 mCi Samarium-153 hydroxyapatite plus 40 mg of triamcinolone hexacetonide (Sm/TH Group), or 40 mg triamcinolone hexacetonide alone (Control Group). Blinded examination at baseline, 1, 4, 12, 32, and 48 weeks post-intervention included a visual analog scale for joint pain and swelling, morning stiffness, range of motion, knee circumference, Likert scale, percentage of improvement, Stanford Health Assessment Questionnaire, Lequesne index, use of non-steroidal anti-inflammatory drugs and corticosteroids, events and adverse effects, calls to the physician, and hospital visits. There were three withdrawals prior to the injections. Regarding the pain, there was a significantly better response in the Y/TH Group versus the Sm/TH Group at T1 (p = 0.025) and versus TH alone at T48 (p = 0.026). The Sm/TH group had more adverse effects (p = 0.042), but these were mild and transitory. For the pain parameter alone, Yttrium-90 radiosynovectomy associated to TH proved superior to Samarium-153 hydroxyapatite radiosynovectomy associated to TH at T1 and to synovectomy with TH at T48. No other statistically significant inter-group differences were detected.