Protein kinase C delta mediates Pasireotide effects in an ACTH-secreting pituitary tumor cell line.

PURPOSE: Clinical control of corticotroph tumors is difficult to achieve since they usually persist or relapse after surgery. Pasireotide is approved to treat patients with Cushing's disease for whom surgical therapy is not an option. However, Pasireotide seems to be effective only in a sub-set of patients, highlighting the importance to find a response marker to this approach. Recent studies demonstrated that the delta isoform of protein kinase C (PRKCD) controls viability and cell cycle progression of an in vitro model of ACTH-secreting pituitary tumor, the AtT-20/D16v-F2 cells. This study aims at exploring the possible PRKCD role in mediating Pasireotide effects. METHODS: It was assessed cell viability, POMC expression and ACTH secretion in AtT20/D16v-F2 cells over- or under-expressing PRKCD. RESULTS: We found that Pasireotide significantly reduces AtT20/D16v-F2 cell viability, POMC expression and ACTH secretion. In addition, Pasireotide reduces miR-26a expression. PRKCD silencing decreases AtT20/D16v-F2 cell sensitivity to Pasireotide treatment; on the contrary, PRKCD overexpression increases the inhibitory effects of Pasireotide on cell viability and ACTH secretion. CONCLUSION: Our results provide new insights into potential PRKCD contribution in Pasireotide mechanism of action and suggest that PRKCD might be a possible marker of therapeutic response in ACTH-secreting pituitary tumors.

ATPergic signaling disruption in human sepsis as a potential source of biomarkers for clinical use.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated inflammatory response to infection. To date, there is no specific treatment established for sepsis. In the extracellular compartment, purines such as adenosine triphosphate (ATP) and adenosine play essential roles in the immune/inflammatory responses during sepsis and septic shock. The balance of extracellular levels among ATP and adenosine is intimately involved in the signals related to immune stimulation/immunosuppression balance. Specialized enzymes, including CD39, CD73, and adenosine deaminase (ADA), are responsible to metabolize ATP to adenosine which will further sensitize the P2 and P1 purinoceptors, respectively. Disruption of the purinergic pathway had been described in the sepsis pathophysiology. Although purinergic signaling has been suggested as a potential target for sepsis treatment, the majority of data available were obtained using pre-clinical approaches. We hypothesized that, as a reflection of deregulation on purinergic signaling, septic patients exhibit differential measurements of serum, neutrophils and monocytes purinergic pathway markers when compared to two types of controls (healthy and ward). It was observed that ATP and ADP serum levels were increased in septic patients, as well as the A2a mRNA expression in neutrophils and monocytes. Both ATPase/ADPase activities were increased during sepsis. Serum ATP and ADP levels, and both ATPase and ADPase activities were associated with the diagnosis of sepsis, representing potential biomarkers candidates. In conclusion, our results advance the translation of purinergic signaling from pre-clinical models into the clinical setting opening opportunities for so much needed new strategies for sepsis and septic shock diagnostics and treatment.

Machine-learning algorithm in acute stroke: real-world experience.

AIM: To assess the clinical performance of a commercially available machine learning (ML) algorithm in acute stroke. MATERIALS AND METHODS: CT and CT angiography (CTA) studies of 104 consecutive patients (43 females, age range 19-93, median age 62) performed for suspected acute stroke at a single tertiary institution with real-time ML software analysis (RAPID™ ASPECTS and CTA) were included. Studies were retrospectively reviewed independently by two neuroradiologists in a blinded manner. RESULTS: The cohort included 24 acute infarcts and 16 large vessel occlusions (LVO). RAPID™ ASPECTS interpretation demonstrated high sensitivity (87.5%) and NPV (87.5%) but very poor specificity (30.9%) and PPV (30.9%) for detection of acute ischaemic parenchymal changes. There was a high percentage of false positives (51.1%). In cases of proven LVO, RAPID™ ASPECTS showed good correlation with neuroradiologists' blinded independent interpretation, Pearson correlation coefficient = 0.96 (both readers), 0.63 (RAPID™ vs reader 1), 0.69 (RAPID™ vs reader 2). RAPID™ CTA interpretation demonstrated high sensitivity (92.3%), specificity (85.3%), and negative predictive (NPV) (98.5%) with moderate positive predictive value (PPV) (52.2%) for detection of LVO (N=13). False positives accounted for 12.5% of cases, of which 27.3% were attributed to arterial stenosis. CONCLUSION: RAPID™ CTA was robust and reliable in detection of LVO. Although demonstrating high sensitivity and NPV, RAPID™ ASPECTS interpretation was associated with a high number of false positives, which decreased clinicians' confidence in the algorithm. However, in cases of proven LVO, RAPID™ ASPECTS performed well and had good correlation with neuroradiologists' blinded interpretation.

Efecto in vitro de 2 compuestos bioactivos, el ácido gálico y el galato de metilo, sobre la urolitiasis / In vitro effects of 2 bioactive compounds, gallic acid and methyl gallate, on urolithiasis

Introducción y objetivos: El objetivo de este estudio fue evaluar el papel de 2 compuestos fenólicos naturales ampliamente distribuidos, el ácido gálico (AG) y el galato de metilo (GM), en un modelo in vitro de urolitiasis, utilizando la metodología de formación de cristales de oxalato de calcio, el tipo más común de cálculos urinarios o renales.Material y métodosLos compuestos AG y GM fueron sometidos a actividades de «anticristalización» en diferentes concentraciones (0,003-0,03mg/mL), y la cantidad y morfología de los cristales se determinó por microscopia después de 60min.ResultadosEl AG inhibió alrededor del 44-57% de la formación total de cristales de cristales de oxalato de calcio, mientras que el GM inhibió alrededor del 48,35%, en comparación con las muestras expuestas al vehículo (agua destilada; grupo de control negativo). La exposición a AG y GM inhibió la formación de cálculos de tipo monohidrato, considerada la categoría de cristales más común y dañina. Los compuestos también disminuyeron la absorbancia, lo que a su vez está relacionado con una reducción de la agregación y precipitación de cristales de oxalato de calcio.ConclusionesEn conjunto, este estudio muestra, por primera vez, que el AG y el GM son compuestos prometedores con propiedades antiurolitiásicas, brindando nuevas perspectivas para futuros estudios in vivo del potencial de estos compuestos en el tratamiento y/o prevención de los cálculos urinarios o renales. (AU)

Introduction and objectives: This study aimed to evaluate the role of 2 widely distributed natural phenolic compounds, gallic acid (GA) and methyl gallate (MG), in an in vitro model of urolithiasis, by using the methodology of calcium oxalate crystals formation, which is the most common type of urinary or kidney stones.Material and methodsThe compounds GA and MG were subjected to anti-crystallization activities in different concentrations (0.003-0.03mg/mL), and the quantity and morphology of crystals were determined by microscopy after 60min.ResultsGA inhibited about 44-57% of the total calcium oxalate crystals formation, while MG inhibited about 48.35%, when compared to vehicle-exposed samples (distilled water; negative control group). GA and MG exposure inhibited monohydrate type calculi formation, which is considered the most common and harmful crystal category. The compounds also decreased absorbance, which in turn is related to reduced calcium oxalate crystals aggregation and precipitation.ConclusionsAltogether, this study shows, for the first time, that GA and MG are promising compounds with antiurolithiatic properties, opening new perspectives for future in vivo evaluations of the potential of these compounds in the treatment and/or prevention of urinary or kidney stones. (AU)

In vitro effects of two bioactive compounds, gallic acid and methyl gallate, on urolithiasis.

INTRODUCTION AND OBJECTIVES: This study aimed to evaluate the role of two widely distributed natural phenolic compounds, gallic acid (GA) and methyl gallate (MG), in an in vitro model of urolithiasis, by using the methodology of calcium oxalate (CaOx) crystals formation, which is the most common type of urinary or kidney stones. MATERIAL AND METHODS: The compounds GA and MG were subjected to anti-crystallization activities in different concentrations (0.003-0.03 mg/mL), and the quantity and morphology of crystals were determined by microscopy after 60 min. RESULTS: GA inhibited about 44-57% of the total CaOx crystals formation, while MG inhibited about 48.35%, when compared to vehicle-exposed samples (distilled water; negative control group). GA and MG exposure inhibited monohydrate type calculi formation, which is considered the most common and harmful crystal category. The compounds also decreased absorbance, which in turn is related to reduced CaOx aggregation and precipitation. CONCLUSIONS: Altogether, this study shows, for the first time, that GA and MG are promising compounds with antiurolithiatic properties, opening new perspectives for future in vivo evaluations of the potential of these compounds in the treatment and/or prevention of urinary or kidney stones.

Genetic associations of fatigue and other symptoms following breast cancer treatment: A prospective study.

BACKGROUND: Cancer-related fatigue, mood disturbances, pain and cognitive disturbance are common after adjuvant cancer therapy, but vary considerably between individuals despite common disease features and treatment exposures. A genetic basis for this variability was explored in a prospective cohort. METHODS: Physical and psychological health of women were assessed prospectively following therapy for early stage breast cancer with self-report questionnaires. Participation in a genetic association sub-study was offered. Indices for the key symptom domains of fatigue, pain, depression, anxiety, and neurocognitive difficulties were empirically derived by principal components analysis from end-treatment questionnaires, and then applied longitudinally. Genetic associations were sought with functional single nucleotide polymorphisms (SNPs) in pro- and anti-inflammatory cytokine genes - tumour necrosis factor (TNF)-α (-308 â€‹GG), interferon (IFN)-É£ (+874 â€‹TA), interleukin (IL)-10 (1082 â€‹GA and -592 CA), IL-6 (-174 â€‹GC), IL-1ß (-511 â€‹GA). RESULTS: Questionnaire data was available for 210 participants, of whom 111 participated in the genetic sub-study. As expected, symptom domain scores generally improved over several months following treatment completion. Tumour and adjuvant treatment related factors were unassociated with either severity or duration of the individual symptom domains, but severity of symptoms at end-treatment was strongly associated with duration for each domain (all p â€‹< â€‹0.05). In multivariable analyses, risk genotypes were independently associated with: fatigue with IL-6 -174 â€‹GG/GC and IL-10 -1082 GG; depression and anxiety with IL-10 -1082 AA; neurocognitive disturbance: TNF-α -308 GG; depression IL-1ß (all p â€‹< â€‹0.05). The identified SNPs also had cumulative effects in prolonging the time to recovery from the associated symptom domain. CONCLUSIONS: Genetic factors contribute to the severity and duration of common symptom domains after cancer therapy.

In vitro effects of 2 bioactive compounds, gallic acid and methyl gallate, on urolithiasis. / Efecto in vitro de 2 compuestos bioactivos, el ácido gálico y el galato de metilo, sobre la urolitiasis.

INTRODUCTION AND OBJECTIVES: This study aimed to evaluate the role of 2 widely distributed natural phenolic compounds, gallic acid (GA) and methyl gallate (MG), in an in vitro model of urolithiasis, by using the methodology of calcium oxalate crystals formation, which is the most common type of urinary or kidney stones. MATERIAL AND METHODS: The compounds GA and MG were subjected to anti-crystallization activities in different concentrations (0.003-0.03mg/mL), and the quantity and morphology of crystals were determined by microscopy after 60min. RESULTS: GA inhibited about 44-57% of the total calcium oxalate crystals formation, while MG inhibited about 48.35%, when compared to vehicle-exposed samples (distilled water; negative control group). GA and MG exposure inhibited monohydrate type calculi formation, which is considered the most common and harmful crystal category. The compounds also decreased absorbance, which in turn is related to reduced calcium oxalate crystals aggregation and precipitation. CONCLUSIONS: Altogether, this study shows, for the first time, that GA and MG are promising compounds with antiurolithiatic properties, opening new perspectives for future in vivo evaluations of the potential of these compounds in the treatment and/or prevention of urinary or kidney stones.

TLR4 expression and functionality are downregulated in glioblastoma cells and in tumor-associated macrophages: A new mechanism of immune evasion?

Glioblastoma (GB) is the most common and aggressive form of primary brain tumor, in which the presence of an inflammatory environment, composed mainly by tumor-associated macrophages (TAMs), is related to its progression and development of chemoresistance. Toll-Like Receptors (TLRs) are key components of the innate immune system and their expression in both tumor and immune-associated cells may impact the cell communication in the tumor microenvironment (TME), further modeling cancer growth and response to therapy. Here, we investigated the participation of TLR4-mediated signaling as a mechanism of induced-immune escape in GB. Initially, bioinformatics analysis of public datasets revealed that TLR4 expression is lower in GB tumors when compared to astrocytomas (AST), and in a subset of TAMs. Further, we confirmed that TLR4 expression is downregulated in chemoresistant GB, as well as in macrophages co-cultured with GB cells. Additionally, TLR4 function is impaired in those cells even following stimulation with LPS, an agonist of TLR4. Finally, experiments performed in a cohort of clinical primary and metastatic brain tumors indicated that the immunostaining of TLR4 and CD45 are inversely proportional, and confirmed the low TLR4 expression in GBs. Interestingly, the cytoplasmic/nuclear pattern of TLR4 staining in cancer tissues suggests additional roles of this receptor in carcinogenesis. Overall, our data suggest the downregulation of TLR4 expression and activity as a strategy for GB-associated immune escape. Additional studies are necessary to better understand TLR4 signaling in TME in order to improve the benefits of immunotherapy based on TLR signaling.

A tool to predict survival in stage IV entero-pancreatic NEN.

PURPOSE: Well-differentiated stage IV neuroendocrine neoplasms (NEN) have an extremely heterogeneous, unpredictable clinical behavior. Survival prognostic markers, such as the recently proposed NEP-Score, would be very useful for better defining therapeutic strategies. We aim to verify NEP-Score applicability in an independent cohort of stage IV well-differentiated (WD) gastroentero-pancreatic (GEP) NEN, and identify a derivate prognostic marker taking into account clinical and pathological characteristics at diagnosis. METHODS: Age, site of primary tumor, primary tumor surgery, symptoms, Ki67, timing of metastases of 27 patients (10 females; mean age at diagnosis 60.2 ± 2.9 years) with stage IV WD GEP NEN were evaluated to calculate the NEP-Score at the end of follow-up (NEP-T). We calculated the NEP-Score at diagnosis (NEP-D), which does not consider the appearance of new metastases during follow-up. Patients were subdivided according to whether they were alive or not at the end of follow-up (EOF) and an NEP-Score threshold was investigated to predict survival. RESULTS: Mean NEP-T and mean NEP-D were significantly lower in 15 live patients as compared to 12 deceased patients (p < 0.01) at EOF. We identified an NEP-D = 116 as the cutoff that significantly predicts survival. No gender differences were identified. CONCLUSIONS: In our series, we confirmed NEP-Score applicability. In addition, we propose NEP-D as a simple, quick and cheap prognostic score that can help clinicians in decision making. NEP-D threshold can predict NEN aggressiveness and may be used to define the best personalized therapeutic strategy.

Is Dexamethasone superior to Ketorolac in reducing pain, swelling and trismus following mandibular third molar removal? A split mouth triple-blind randomized clinical trial.

BACKGROUND: The preemptive use of anti-inflammatory drugs, such as corticosteroids and NSAIDs, has the potential to reduce pain, swelling and trismus following oral surgery. The aim of this study was to compare the efficacy of dexamethasone and ketorolac tromethamine in reducing pain, swelling and trismus after mandibular third molar removal. MATERIAL AND METHODS: The researches implemented a triple-blind, randomized clinical trial. The study was conducted with ASA I individuals aging between 18 and 35 years, which were randomized and submitted to two interventions, one with 8mg dexamethasone and the other with 20mg ketorolac tromethamine given 1h before the procedure. The primary predictor variable was the use of dexamethasone or ketorolac. The primary outcome variable was the postoperative pain level, measured with a Visual Analogue Scale. The secondary outcome variables were the amount of rescue analgesic consumed, swelling and trismus. Repeated-measures ANOVA and t-test for paired samples were used to compare the means. Significance was set at p < 0.05. RESULTS: Fifty individuals were randomized and allocated to intervention, and the sample was composed of 40 subjects who completed the study (27 female and 13 male). Dexamethasone, when compared to ketorolac tromethamine, showed a significantly higher reduction in pain level at 8h, 16h, 24h, 32h, 40h and 72h, in swelling and trismus at 24h, 48h, 72h and 7 days and in total number of rescue analgesics taken up to 72h postoperative (p < 0.05). CONCLUSIONS: The clinical performance of dexamethasone in controlling pain, swelling and trismus after mandibular third molar removal was superior to ketorolac tromethamine's.

A critical appraisal of evidence in the use of preprocedural mouthwash to avoid SARS-CoV-2 transmission during oral interventions.

OBJECTIVE: The study aimed to review and report the current evidence supporting the use of mouthwashes as a preprocedural protocol on dental offices. MATERIALS AND METHODS: This study is a secondary one that performed a comprehensive literature search of scientific studies published up to 10th August 2020 in PubMed, Scopus, Web of Science, and Scientific Electronic Library Online (Scielo) databases. The electronic search strategy was performed using free text and DeCS/MeSH terms. RESULTS: Only five studies were included in this work, despite 140 studies that were identified with the research strategy. In vivo studies were carried out in two works, in vitro studies were described in two papers, and a in silico approach was used in one work. No cetylpyridinium chloride studies were identified, while chlorhexidine and povidone studies were more studied. CONCLUSIONS: There is reduced evidence about how preprocedural mouthwashes decrease SARS-CoV-2 salivary load.

Prevalence of ulcerative stomatitis in arbovirus infections in a Brazilian Northeast population.

BACKGROUND: Although there are no population-based studies that support an association, there are reports in the literature of mucocutaneous, vesiculobullous and ulcerated lesions in the oral mucosa in cases of arbovirus infection. The aim of this study is to analyze the prevalence of ulcerative stomatitis in individuals affected by arboviruses in a population of the municipality of Arcoverde, Pernambuco, Brazil. MATERIAL AND METHODS: 1,003 people living in an area assigned to a Primary Health Care Unit were interviewed. A structured questionnaire was used for data collection, with questions about sociodemographic variables, residence conditions, general health information, as well as information about the general signs and symptoms of arboviruses and specifically about oral lesions. RESULTS: Of the 1,003 individuals interviewed, 815 (81.25%) were infected by one or more arboviruses. Of these, 147 (18%) reported ulcerated oral lesions during arbovirus infections. The association between arbovirus infections and the presence of ulcerated oral lesions was statistically significant (p = 0.000). CONCLUSIONS: In these cases, the ulcerated lesions on the oral mucosa appear to be associated with arbovirus infection, especially Chikungunya, although the pathophysiological mechanisms are not defined, and the studies are not sufficient to confirm this association.

Furoxan derivatives demonstrated in vivo efficacy by reducing Mycobacterium tuberculosis to undetectable levels in a mouse model of infection.

OBJECTIVES: The most recent survey conducted by the World Health Organization described Tuberculosis (TB) as one of the top 10 causes of death and the leading cause of death from a single infectious agent. The increasing number of TB-resistant cases has contributed to this scenario. In light of this, new strategies to control and treat the disease are necessary. Our research group has previously described furoxan derivatives as promising scaffolds to be explored as new antitubercular drugs. RESULTS: Two of these furoxan derivatives, (14b) and (14c), demonstrated a high selectivity against Mycobacterium tuberculosis. The compounds (14b) and (14c) were also active against a latent M. tuberculosis strain, with MIC90 values of 6.67 µM and 9.84 µM, respectively; they were also active against monoresistant strains (MIC90 values ranging from 0.61 to 20.42 µM) and clinical MDR strains (MIC90 values ranging from 3.09 to 42.95 µM). Time-kill experiments with compound (14c) showed early bactericidal effects that were superior to those of the first- and second-line anti-tuberculosis drugs currently used in therapy. The safety of compounds (14b) and (14c) was demonstrated by the Ames test because these molecules were not mutagenic under the tested conditions. Finally, we confirmed the safety, and high efficacy of compounds (14b) and (14c), which reduced M. tuberculosis to undetectable levels in a mouse aerosol model of infection. CONCLUSION: Altogether, we have identified two advanced lead compounds, (14b) and (14c), as novel promising candidates for the treatment of TB infection.

The centrality of workers to sustainability based on values: Exploring ergonomics to introduce new rationalities into decision-making processes.

This article presents the results of an academic research project connecting the discipline of ergonomics (and work-related issues) with the theme of sustainability. Despite the stated aim of creating value for stakeholders, including employees, companies face difficulties in introducing effective sustainability policies. The research question addressed in this article is the following: How can companies improve their decision-making processes to increase workers' wellbeing using policies integrating issues related to corporate sustainability and ergonomics? Currently, corporate sustainability is focused mainly on the triple bottom line (TBL) concept. In this context, the integration of ergonomics is fragmented and arguably separate from strategic human-resource functions (which have largely been the primary promoter of the internal-social component of corporate sustainability). This research argues that corporate sustainability requires a new step, improving the decision-making process, with the inclusion of more types of rationalities and the recognition of the centrality of workers in the process of creating sustainable action. When corporate sustainability policies focus on worker centrality, they open space for the integration of ergonomics as a pillar of an organization's corporate sustainability strategy. Based on a complex view of work systems, ergonomics can introduce values aligned with sustainability and promote cooperation in organizations. Different stakeholders working at companies can make use of different concepts proposed by ergonomics and other work sciences to support changes in their decision-making processes. In view of broader sustainability objectives, integrating different work-related considerations can help improve performance, including productivity, quality and health.

Pain during and after-hernioplasty in raquidian or locorregional anesthesia by locking peripheral nerves.

PURPOSE: To analyze pain scores after surgery in a group of patients submitted to inguinal hernia repair under peripheral nerve block with local or spinal anesthesia. METHODS: Fifty patients were divided into two groups (both with 25 patients each). In the first group the patients were submitted to herniorrhaphy under peripheral block and local anesthesia (LG) and in the other group the patients were submitted to the same procedure under spinal anesthesia (RG). The pain was assessed using the international visual analog pain scale at four different moments. The analysis cost of the procedure was performed using the hospital's average final cost, without including medical expenses. RESULTS: The groups were homogeneous in relation to the epidemiological and clinical features. There was no significant difference between the pain in the intraoperative period and in the return visit for both groups (p = 0.17 and p = 0.18). In the immediate postoperative period, both groups reported no pain at all. In general, the RG reported a greater pain score (16% for RG and 12% for LG). Complications were more frequent in patients submitted to spinal anesthesia (40% versus 8%) (p = 0.008). The surgical time was higher in the LG (39.3 ± 9.2 min) versus (28.7 ± 7.5 min) (p = 0.01). The average final cost of the procedure was US$ 100.98 for the LG and US$ 166.19 for the RG (p = 0.00). CONCLUSION: The inguinal hernioplastia under local anesthesia plus sedation is a safe method, with a low incidence of complications, great acceptance by patients and less expensive.

The predictive and prognostic significance of liquid biopsy in advanced epidermal growth factor receptor-mutated non-small cell lung cancer: A prospective study.

OBJECTIVE: To determine the predictive and prognostic roles of three blood-based biomarkers: circulating tumour DNA (ctDNA), circulating tumour cells (CTC) and carcinoembryonic antigen (CEA), in patients with advanced epidermal growth factor receptor-mutated (EGFR+) lung cancer. MATERIALS AND METHODS: We recruited 28 patients with 103 serial blood samples. We performed mutational analyses for EGFR mutations using droplet digital PCR (ddPCR) on ctDNA. We evaluated the accuracy of EGFR mutation detection in ctDNA compared with tissue biopsy. We also quantified CTCs, ctDNA and CEA in serially collected blood samples, and evaluated the baseline and changes in these blood-based biomarkers with clinical outcomes. RESULTS: EGFR mutation detection in plasma was highly concordant as compared with tissue biopsy. Detectable baseline ctDNA was associated with higher disease burden (p < 0.01). Early disappearance of ctDNA at 4 weeks was associated with radiological response at 12 weeks of treatment (p = 0.01) and improved progression free survival (PFS) (HR 5.47, 95%CI 1.32-22.72, p = 0.02) and overall survival (OS) (HR 5.46, 95%CI 1.28-23.22, p = 0.02). A decrease in CTC count at 4 weeks was associated with improved PFS (HR 3.81, 95%CI 1.13-12.79, p = 0.03) but not OS. 85% of patients with radiological progression had a ctDNA rise compared with 22% of patients with stable disease (p=0.01). ctDNA rise was seen on average 170 days prior to radiological progression. There is a significant association between the rise of CEA level with radiological progression (p=0.001). CONCLUSION: Early change in ctDNA, CTC and CEA levels may be long-term predictors of treatment benefit and failure prior to availability of radiological response data.

Reproducibility of quantitative sensory testing applied to musculoskeletal orofacial region: Site and sex differences.

BACKGROUND: This study estimated the inter-rater reliability and agreement of the somatosensory assessment performed at masseter and temporomandibular joint (TMJ) region in a group of healthy female and male participants. METHODS: Forty healthy participants (20 men and 20 women) were evaluated in two sessions by two different examiners. Cold detection threshold (CDT), warm detection threshold (WDT), thermal sensory limen (TSL), cold pain threshold (CPT), heat pain threshold (HPT), mechanical detection threshold (MDT), mechanical pain threshold (MPT), wind-up ratio (WUR) and pressure pain threshold (PPT) were assessed on the skin overlying TMJ and masseter body. Mixed ANOVA, intraclass correlation coefficients (ICC) and standard error of measurement (SEM) were applied to the data (α = 5%). Nonoverlapping 95% confidence intervals (95% CI) of ICCs were considered significantly different. RESULTS: The ICCs of 77% of all quantitative sensory testing (QST) measurements were considered fair to excellent (ICCs: 0.47-0.97), and WUR presented the lowest values. The reliability of WDT, TSL and HPT of masseter was significantly higher than TMJ, whereas the MDT reliability of TMJ was higher than masseter. In addition, the following combination of test/sites presented significantly lower ICCs for women: HPT, MDT of TMJ and MPT of both TMJ and masseter. Finally, the highest SEM values were presented for CPT and MPT. CONCLUSION: The overall somatosensory assessment of the masticatory structures performed by two examiners can be considered sufficiently reliable to discriminate participants, except WUR. Possible site and sex influences on the reproducibility parameters should be taken into account for an appropriate interpretation and clinical application of QST. SIGNIFICANCE: The test site and participant's sex can significantly influence the relative reliability and agreement of quantitative sensory testing applied to musculoskeletal orofacial region, which affect the capacity to discriminate participants and to evaluate changes over time.

New findings in facial-onset sensory and motor neuronopathy (FOSMN) syndrome.

Facial-onset sensory and motor neuronopathy (FOSMN) syndrome represents a rare, slowly progressive, lower motor neuron disease with sensory compromise, involving mainly the face, bulbar region and upper limbs. However, non-motor symptoms and neurogenetic studies have rarely been evaluated in large case series. In the present study, 10 unrelated Brazilian patients with FOSMN syndrome underwent extensive clinical, laboratory, neurophysiological and neurogenetic assessment. Median age at symptom onset was 52.1 years, and men and women were equally affected. Patients presented with hemifacial or bilateral facial paresthesia and weakness, which evolved with dysphagia, dysphonia, and facial and tongue atrophy and, finally, a dropped-head, upper limb weakness and syringomyelia-like sensory disturbances in the upper limbs. All 10 patients showed chronic diffuse neurogenic compromise of bulbar, cervical and thoracic myotomes, and abnormal blink reflex tests. A positive family history of neurodegeneration was identified in six cases, and revealed pathogenic gene variants in three families (involving VCP, TARDBP and CHCHD10). Thus, our case series has revealed new findings regarding FOSMN syndrome: (i) its clinical course is not always benign, with poorer prognoses associated with dropped-head syndrome and early bulbar compromise; (ii) FOSMN syndrome may be part of a complex familial neurodegenerative spectrum; and (iii) a definite genetic basis may be observed in some cases.

Cannabinoid CB1 Receptor Antagonist Rimonabant Decreases Levels of Markers of Organ Dysfunction and Alters Vascular Reactivity in Aortic Vessels in Late Sepsis in Rats.

Sepsis is a life-threatening condition with high mortality rates that is caused by dysregulation of the host response to infection. We previously showed that treatment with the cannabinoid CB1 receptor antagonist rimonabant reduced mortality rates in animals with sepsis that was induced by cecal ligation and puncture (CLP). This improvement in the survival rate appeared to be related to an increase in arginine vasopressin (AVP) levels 12 h after CLP. The present study investigated the effects of rimonabant on organ dysfunction, hematologic parameters, and vascular reactivity in male Wistar rats with sepsis induced by CLP. Intraperitoneal treatment with rimonabant (10 mg/kg, 4 h after CLP) abolished the increase in the plasma levels of lactate, lactate dehydrogenase, glucose, and creatinine kinase MB without altering hematological parameters (i.e., leukopenia and a reduction of platelet counts). CLP increased plasma levels of nitrate/nitrite (NOx) and induced vasoconstriction in the tail artery. The treatment of CLP rats with rimonabant did not alter NOx production but reduced the vasoconstriction. Rimonabant also attenuated the hyperreactivity to AVP induced by CLP without affecting hyporesponsiveness to phenylephrine in aortic rings. These results suggest that rimonabant reduces organ dysfunction during sepsis, and this effect may be related to AVP signaling in blood vessels. This effect may have contributed to the higher survival rate in rimonabant-treated septic animals.

Knowledge Among University Students in Rio de Janeiro Regarding Transplant Organ Donation.

INTRODUCTION: Organ transplantation is often the only possible treatment to save the lives of patients with end-stage organ failure. Limiting factors include failure to notify in cases of patients with brain death, the inefficient procurement and distribution of organs, the lack of specific educational policies for health care professionals, lack of knowledge on the organ transplantation process, and family refusal for organ donation. OBJECTIVE: To evaluate the knowledge of students enrolled in different undergraduate university courses in Rio de Janeiro on the regulations and strategies governing transplant organ donation in Brazil. METHODS: This qualitative, observational study used a 10-item questionnaire aimed at obtaining data on respondents' general knowledge regarding organ donation and transplantation. The questionnaire was applied using either a printed or an electronic version developed on Google Forms and was completed anonymously. RESULTS: Overall, 587 questionnaires were completed. The participants were divided into 3 groups according to their field of study: 256 (43.6%) from courses related to arts and humanities, 159 (27.1%) from science and technology-related courses, and 172 (29.3%) from the biomedical field. Most respondents (396; 67.5%) were unaware of the criteria required to be an organ transplant donor. CONCLUSION: There is a significant lack of knowledge among university students on issues related to the organ donation and transplantation process in Brazil.