Surgical frontiers in war zones: perspectives and challenges of a humanitarian surgeon in conflict environments.

This opinion article delves into the complexities of surgical care in conflict zones, highlighting the challenges and ethical considerations faced by humanitarian surgeons. It emphasizes the importance of collaboration with local healthcare professionals and specialized training programs in preparing surgeons for the unique demands of conflict trauma and war surgery.

Morpho-Physiological Evaluation of Solanum betaceum Cav. In Vitro Cloned Plants: A Comparison of Different Micropropagation Methods.

Tamarillo (Solanum betaceum Cav.) is a subtropical solanaceous tree with increasing agronomic interest due to its nutritious edible fruits. Growing demand for tamarillo plants and fruits requires optimization of existing propagation methods and scaled-up systems for large-scale cloning of selected germplasm. Three in vitro protocols have been used to micropropagate tamarillo: (1) axillary shoot proliferation in a semisolid medium, (2) organogenesis, and (3) somatic embryogenesis procedures. Variables such as the age of the established shoot cultures and rooting treatments were also analyzed. The morphological and physiological quality of acclimatized plants derived from all the methodologies were compared, with seed-derived plants used as a control group. Overall, the results show that in vitro-derived plants have a similar development to seed-derived plants. Micropropagation by axillary shoot proliferation was highly efficient, with rooting rates above 80% in most treatments. Organogenesis induction was more effective from lamina explants using MS media with 2.0 mg·L-1 6-benzylaminopurine. Both organogenesis and somatic embryogenesis-derived plants were also morphologically and physiologically equivalent to seed and axillary shoot-derived plants. The specificities of each micropropagation method are discussed.

Targeted Axillary Dissection after Chemotherapy: Feasibility Study with Clip and Carbon Dye Tattoo - Neotarget Trial.

Background: Axillary staging in patients with complete response after neoadjuvant chemotherapy (NAC) is still controversial. Our objective was to test tattoo alone and subsequentially tattoo plus clip as markers in the targeted axillary dissection of ycN0 patients. Methods: Prospective cohort of cT1-T3, cN1 (proven histologically), M0 patients scheduled to receive NAC. Exclusion criteria were lobular histology, prior axillary surgery, and clinical N2/3. In cohort 1 this positive node (Neotarget node) was tattooed at diagnosis. If ycN0, a targeted axillary dissection was performed. After an interim analysis with negative results we changed the protocol in order to do a double marking procedure (Cohort 2): the positive node was clipped at diagnosis and after NAC a tattoo was done before surgery. Results: Thirteen patients in Cohort 1 and 18 patients in Cohort 2. Failure to identify the Neotarget node with multiple nodes retrieved in 9/13 (69%) of Cohort 1 patients. Also in 5/13 (38%) of Cohort 1 patients and 3/18 (17%) of Cohort 2 there was a failure to clearly identify tattooed nodes. In Cohort 2, clip identification by surgical specimen radiography allowed the identification of the tagged node in 17/18 (94,4%) of cases. The concordance between the clipped node and sentinel nodes was 16/18 (89%). Conclusions: The introduction of double marking by clipping the metastatic node and verifying their removal by surgical specimen radiography, using carbon ink as a tracer, allowed the identification of the metastatic node in 94% of cases, with a simple, reproducible, and easy-to-implement targeted axillary dissection procedure.

Staging of Endometrial Cancer Using Fusion T2-Weighted Images with Diffusion-Weighted Images: A Way to Avoid Gadolinium?

Endometrial cancer is the eighth most common cancer worldwide, and its prognosis depends on various factors, with myometrial invasion having a major impact on prognosis. Optimizing MRI protocols is essential, and it would be useful to improve the diagnostic accuracy without the need for other sequences. We conducted a retrospective, single-center study, which included a total of 87 patients with surgically confirmed primary endometrial cancer, and who had undergone a pre-operative pelvic MRI. All exams were read by an experienced radiologist dedicated to urogenital radiology, and the depth of myometrial invasion was evaluated using T2-Weighted Images (T2WI) and fused T2WI with Diffusion-Weighted Images (DWI). Both results were compared to histopathological evaluations. When comparing both sets of imaging (T2WI and fused T2WI-DWI images) in diagnosing myometrial invasion, the fused images had better accuracy, and this difference was statistically significant (p < 0.001). T2WI analysis correctly diagnosed 82.1% (70.6-88.7) of cases, compared to 92.1% correctly diagnosed cases with fused images (79.5-97.2). The addition of fused images to a standard MRI protocol improves the diagnostic accuracy of myometrial invasion depth, encouraging its use, since it does not require more acquisition time.

What we know so far about postural balance training: An exploratory scoping review of nomenclature and related issues.

BACKGROUND: Different terms are used to refer to postural balance training, but the ontological debate involving the concepts to pursue nomenclature consensus is unusual. OBJECTIVE: The goal of this study was to analyze how often the terms balance, neuromuscular, proprioceptive, functional and sensorimotor training/exercise are used in the literature, and to propose a conceptual critical appraisal to determine the most appropriate terminology to address postural balance exercises. METHODS: A literature search was conducted in the Scopus electronic database. Eligibility criteria: papers with the selected expressions on the title or keywords, published in English, were included. RESULTS: The most used term was balance training (471 of 1105 included papers). Europe, followed by Asia and North America, had the highest number of publications. In the 21st century, the number of publications increased considerably. However, the terms have conceptual differences and controversies regarding its use. CONCLUSION: Despite a large variety of exercise types and divergences, balance training seems to be the most suitable term, given it refers to postural equilibrium exercises.

Mídias sociais como fonte de conhecimento para o processo de parto normal / Los medios sociales como fuente de conocimientos para el proceso de parto normal / Social media as a source of knowledge for the process of normal delivery

RESUMO Objetivo: verificar o conhecimento adquirido pelas gestantes para o processo de parto normal através das mídias sociais e a influência sobre a experiência do parto. Metodologia: estudo qualitativo com 12 puérperas de um hospital filantrópico, na cidade de Recife-PE. Foram realizadas entrevistas individuais, entre dezembro de 2018 e fevereiro de 2019, e foi utilizada a metodologia de análise de conteúdo. Resultados: após análise, emergiram duas categorias: Uso da mídia social como suporte de informações durante a gestação, e Expectativa para o parto vaginal através do conhecimento adquirido versus a realidade da experiência do parto vaginal. Conclusão: em resposta ao déficit de educação em saúde, as mídias sociais ganharam espaço como principal fonte de informações e esclarecimento de dúvidas a respeito do parto. Os profissionais da saúde, conhecendo as fontes de informação utilizadas pelas gestantes, podem contribuir com as orientações e indicação de fontes seguras e com conteúdo de qualidade.

RESUMEN: Objetivo: verificar los conocimientos adquiridos por las embarazadas para el proceso de parto normal a través de los medios sociales y la influencia sobre la experiencia del parto. Metodología: estudio cualitativo realizado con 12 puérperas de un hospital filantrópico en la ciudad de Recife-PE. Se realizaron entrevistas individuales entre diciembre de 2018 y febrero de 2019 y se utilizó la metodología del análisis de contenido. Resultados: luego del análisis surgieron dos categorías: Uso de los medios sociales como soporte de información durante el embarazo, y Expectativa con respecto al parto vaginal a través del conocimiento adquirido versus la realidad de la experiencia del parto vaginal. Conclusión: en respuesta al déficit de educación en salud, los medios sociales ganaron espacio como fuente principal de información y aclaración de dudas con respecto al parto. Al conocer qué fuentes de información emplearon las embarazadas, los profesionales de la salud pueden contribuir con pautas orientadoras y con la indicación de fuentes seguras y que aporten contenido de calidad.

ABSTRACT Objective: To check the knowledge acquired by pregnant women through social media about the normal delivery process and the influence on the delivery experience. Method: A qualitative study with 12 puerperal women from a philanthropic hospital, in the city of Recife-PE. Individual interviews were conducted between December 2018 and February 2019, and the methodology of content analysis was used. Results: Two categories emerged after analysis: The use of social media as information sources during pregnancy, and Expectation towards vaginal delivery with the acquired knowledge versus the reality of the vaginal delivery experience. Conclusion: In response to the health education deficit, social media gained ground as the main source of information and clarification of pieces of doubt about childbirth. Health professionals, knowing the sources of information used by pregnant women, can contribute with the guidance and indication of safe sources with quality content.

Continuous spinal anaesthesia for partial gastrectomy in an adult patient with unrepaired tetralogy of Fallot.

Correction of tetralogy of Fallot during infancy usually eliminates the risks associated with general anaesthesia. In rare cases of uncorrected defects persisting into adulthood, anaesthetic management during non-cardiac surgery may therefore be challenging. We describe the use of continuous spinal anaesthesia to successfully circumvent the operative risk of major abdominal surgery in an adult patient with uncorrected tetralogy of Fallot.

Inorganic nitrate prevents the loss of tight junction proteins and modulates inflammatory events induced by broad-spectrum antibiotics: A role for intestinal microbiota?

Upon consumption, dietary nitrate is reduced to nitrite in the oral cavity and to nitric oxide (•NO) in the stomach. Here, •NO increases mucosal blood flow, mucus thickness and prevents microbial infections. However, the impact of nitrate on gut microbiota, a pleiotropic organism essential to maintain gastrointestinal and systemic welfare, remains elusive. This study investigates the impact of nitrate on gut microbiota profile and ensued mucosal effects during dysbiosis. Male Wistar rats were randomly distributed in 4 groups and the drinking water was supplemented for 7 days as follows: 1) antibiotic cocktail (neomycin, bacitracin and imipenem), 2) antibiotic cocktail + sodium nitrate, 3) sodium nitrate and 4) regular drinking water. Animals were weighted daily and feces were collected before and after the treatment. The stomach was isolated and the expression of occludin, claudin-5 as well as myeloperoxidase and iNOS was studied. Bacterial DNA was analyzed in fecal samples by PCR-DGGE genetic fingerprinting. Nitrate prevented antibiotic-induced body weight loss (1.9 ± 1.8% vs 8.9 ±â€¯1.8%, p < 0.05) and cecamegalia (7.1 ±â€¯0.5% vs 5.6 ±â€¯0.4%, p < 0.05). Gastric expression of occludin and claudin-5 tended to decrease during dysbiosis but both protein levels were recovered following nitrate consumption (p < 0.05). Similarly, nitrate inhibited the overexpression of myeloperoxidase and iNOS observed under dysbiosis (p < 0.05). Broad spectrum antibiotics significantly decreased microbiota richness and diversity in comparison to controls (p = 0.0016). After 7 days of treatment, whereas antibiotics reduced microbiota richness by 56%, it was observed that nitrate was able to prevent such microbial loss to only 48%, although without statistical differences (p = 0.068). This data suggests that dietary nitrate may be envisaged as a key component of functional foods with beneficial impact on gastric mucosal integrity during antibiotherapy but further studies are mandatory to better ascertain as to whether it modulates intestinal microbiota in terms of taxonomic and functional levels.

Hesperidin-Loaded Solid Lipid Nanoparticles: Development and Physicochemical Properties Evaluation.

Although nanocarrier systems have been investigated to function as therapeutic delivery agents to specific sites of the body, the drug encapsulation method is not always well elucidated. In this work, solid lipid nanoparticles (SLN) composed by stearic acid or cetostearyl alcohol were prepared by a hot homogenization method using poly(vinyl alcohol) or polysorbate as surfactant and loaded with hesperidin, a bioflavonoid that possesses many pharmacological properties. The obtained SLN were characterized by several physicochemical techniques to identify interactions between the constituents and to evaluate the drug incorporation into the nanoparticles. According to scanning electron microscopy and dynamic light scattering the hesperidin-loaded and unloaded SLN have spherical shapes, sizes ranging from 300 to 600 nm, zeta potentials varying from -35 to -20 mV, polydispersity indexes between 0.240 and 0.445, and entrapment efficiencies higher than 88%. X-ray diffraction showed the hesperidin amorphization due to its encapsulation in SLN, and also showed crystallization degree and polymorphic modification of the lipids after the SLN preparation. FTIR, Raman and Photoacoustic spectroscopy revealed no chemical reactions between drug and lipids, however, these results indicated that the drug was incorporated differently into nanoparticles based on the SLN composition. The analysis showed that stearic acid-based SLN prepared with polysorbate were more efficient to enclosure the hesperidin while the glycosydic part of the hesperidin was not entrapped in the cetostearyl alcohol-based SLN; instead, the hesperidin remained on the SLN surface due to lipid crystallization. The physicochemical characterization allowed identifying different types of hesperidin incorporation into the SLN, which can interact in a varied manner as targeted drug delivery systems.

Avaliação da satisfação de puérperas em relação ao parto / Evaluation about puerperals' satisfaction regarding parturition

Objetivo: analisar a satisfação acerca do trabalho de parto e parto de mulheres que pariram em uma maternidade de alto risco. Método: trata-se de estudo quantitativo, transversal, com 91 puérperas, realizado em um hospital de alta complexidade. Utilizaram-se um questionário sociodemográfico e um modelo adaptado do Questionário de Experiência e Satisfação com o Parto (QUESP). Realizaram-se a análise estatística descritiva e os testes estatísticos de Qui-quadrado e exato de Fisher apresentados em tabelas. Resultados: constataram-se que 61,67% das mulheres apresentaram baixa expectativa e 44%, baixa satisfação em relação ao Trabalho de Parto (TP) e Parto (P). Constatou-se que houve relação estatística significativa entre a expectativa e a satisfação das mulheres com o parto. Conclusão: sugere-se mais investigação sobre essa temática a fim de identificar as determinantes da satisfação, bem como de reorganização da política de assistência obstétrica.(AU)

Ajustes cinemáticos do complexo articular do tornozelo sobre diferentes superfícies instáveis / Kinematic adjustments of the ankle joint complex on different unstable surfaces

INTRODUÇÃO: Poucos estudos discutem as reações corporais de indivíduos saudáveis no momento em que os exercícios em superfícies instáveis estão sendo executados, embora os efeitos do treinamento ­ efeitos crônicos do exercício- sejam bastante estudados. OBJETIVO: Descrever a cinemática articular do tornozelo e retropé durante essa interação. MÉTODOS: Dezoito voluntários participaram do estudo. A posição articular da região do tornozelo foi estudada em três superfícies: Airex® Balance-pad, BOSU® e chão (controle). Para análise estatística, utilizou-se ANOVA e Pós-teste de Tuckey, considerando um nível de significância menor que 0,05. RESULTADOS: A posição articular da região tornozelo no plano sagital foi diferente no BOSU® em relação ao Airex® (p < 0.001) e ao chão (p < 0.001). O tornozelo ficou em posição mais próxima à neutra no AIREX® e no chão. Com o BOSU, a dorsiflexão foi acentuada. Não houve diferença da posição média no no plano frontal. A variabilidade da posição da região do tornozelo foi maior no BOSU® que no Airex® (p < 0.001) e no chão (p < 0.001), tanto no plano sagital, quanto no plano frontal. A frequência média de deslocamento da posição articular na região do tornozelo no plano sagital foi maior no BOSU® que no chão (p < 0.001); e no plano frontal, para o retropé, foi maior no BOSU® que no Airex® (p < 0.001) e chão (p < 0.001). CONCLUSÃO: Houve diferença no comportamento articular da região do tornozelo na condição BOSU® em relação às demais nas superfícies utilizadas, havendo um aumento das oscilações articulares no processo de controle postural em condições mais instáveis e maior dosiflexão no BOSU®. [AU]

INTRODUCTION: There are few studies approaching the bodily reactions of healthy individuals while performing exercises on unstable surfaces, although the training effects ­ exercise chronic effects - are well studied. OBJECTIVE: The goal of this study is to describe the ankle and rear foot region osteoarticular kinematic during this interaction. METHODS: Eighteen volunteers participated in the study. The ankle region osteoarticular displacement was studied in three different surfaces: AIREX® Balance-pad, BOSU® and Ground (control). Statistical analysis was performed using ANOVA and Tukey test, considering a significance level of 0.05. RESULTS: The position of the ankle joint in the sagittal plane was greater in the BOSU® than in the AIREX® (p < 0.001) and ground (p < 0.001). The ankle was close to the neutral position in the AIREX® and on the ground. With BOSU, the dorsiflexion was accentuated. Considering the frontal plane, there was no difference in the rear foot position. Moreover, the variability in the ankle region position in sagittal and frontal planes was higher in BOSU® than AIREX® (p < 0.001) and ground (p < 0.001). The mean frequency of the ankle position in the sagittal plane was greater in the BOSU® than on the ground (p < 0.001), and, in frontal plane, the rear foot frequency displacement was largest in the BOSU® than in the AIREX® (p < 0.001) and on the ground (p < 0.001). CONCLUSION: There were observed differences in ankle region postural control strategies in the BOSU® condition when compared with the other surfaces tested. The ankle and rear foot oscillations increase and there is a greater dorsiflexion for the postural control under the most unstable condition - BOSU. [AU]

Chemoembolization of Hepatocellular Carcinoma with Drug-Eluting Polyethylene Glycol Embolic Agents: Single-Center Retrospective Analysis in 302 Patients.

PURPOSE: To evaluate the efficacy and safety of transarterial chemoembolization with polyethylene glycol (PEG) drug-eluting embolic agents in the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A single-center retrospective study of 302 patients (258 men; 85.4%) with HCC treated during a 20-month period was conducted. The mean patient age was 66 years ± 10; 142 (47%) had Barcelona Clinic Liver Cancer stage A disease and 134 had (44.4%) stage B disease; 174 (57.6%) had a single HCC tumor, 65 (21.5%) had 2, and 62 (20.9%) had 3 or more. Mean index tumor size was 36.6 mm ± 24.8. One-month follow-up computed tomography (CT) response per modified Response Evaluation Criteria In Solid Tumors and clinical and biochemical safety were analyzed. Progression-free and overall survival were calculated by Kaplan-Meier method. RESULTS: Median follow-up time was 11.9 months (95% confidence interval, 11.0-13.0 mo). One-month follow-up CT revealed complete response in 179 patients (63.2%), partial response in 63 (22.3%), stable disease in 16 (5.7%), and progressive disease in 25 (8.8%). The most frequent complications were postembolization syndrome in 18 patients (6%), liver abscess in 5 (1.7%), and puncture-site hematoma in 3 (1%). Biochemical toxicities occurred in 57 patients (11.6%). Survival analysis at 12 months showed a progression-free survival rate of 65.9% and overall survival rate of 93.5%. Patients who received transplants showed a 57.7% rate of complete pathologic response. CONCLUSIONS: Chemoembolization with PEG embolic agents for HCC is safe and effective, achieving an objective response rate of 85.5%.

Microfluidic manufacturing of phospholipid nanoparticles: Stability, encapsulation efficacy, and drug release.

Liposomes have been the centre of attention in research due to their potential to act as drug delivery systems. Although its versatility and manufacturing processes are still not scalable and reproducible. In this study, the microfluidic method for liposomes preparation is presented. DMPC and DSPC liposomes containing two different lipid/cholesterol ratios (1:1 and 2:1) are prepared. Results from this preparation process were compared with the film hydration method in order to understand benefits and drawbacks of microfluidics. Liposomes characterisation was evaluated through stability studies, encapsulation efficacy and drug release profiles of hydrophilic and lipophilic compounds. Stability tests were performed during 3 weeks and the liposomes properties of the most stable formulations were determined using Infrared Microscopy and Atomic Force Microscopy. Microfluidic allows loading of drugs and assembly in a quick single step and the chosen flow ratio for liposomes formulation plays a fundamental role for particle sizes. One hydrophilic and one lipophilic compounds were incorporated showing how formulation and physic-chemical characteristics can influence the drug release profile.

Dietary nitrite induces occludin nitration in the stomach.

The clinical implications of the nitrate-nitrite-nitric oxide pathway have been extensively studied in recent years. However, the physiological impact of bioactive nitrogen oxides produced from dietary nitrate has remained largely elusive. Here, we report a hitherto unrecognized nitrite-dependent nitrating pathway that targets tight junction proteins in the stomach. Inorganic nitrate, nitrite or saliva obtained after the consumption of lettuce were administered by oral gavage to Wistar rats. The enterosalivary circulation of nitrate was allowed to occur for 4 h after which the animals were euthanized and the stomach collected. Nitrated occludin was detected by immunoprecipitation in the gastric epithelium upon inorganic nitrite administration (p < .05) but was not observed in the case of inorganic nitrate or human saliva administration. This observation, along with differences in •NO production rates from inorganic and salivary nitrite under simulated gastric conditions, suggests that competing reactions at acidic pH determine the production of nitrating agents (•NO2) or other, more stable, oxides. Accordingly, it is shown in vitro that salivary nitrite yields higher steady state concentrations of •NO (0.37 ± 0.01 µM) than sodium nitrite (0.12 ± 0.03 µM). Dietary-dependent reactions involving the production of nitrogen oxides should be further investigated as, in the context of occludin nitration, the consumption of green leafy vegetables (with high nitrate content), if able to modulate gut barrier function, may have important implications in the context of leaky gut disorders.

Laparoscopic cholecystectomy under continuous spinal anesthesia in a patient with Steinert's disease / Colecistectomia laparoscópica sob raquianestesia contínua em paciente com doença de Steinert

ABSTRACT Steinert's disease is an intrinsic disorder of the muscle with multisystem manifestations. Myotonia may affect any muscle group, is elicited by several factors and drugs used in general anesthesia like hypnotics, sedatives and opioids. Although some authors recommend the use of regional anesthesia or combined anesthesia with low doses of opioids, the safest anesthetic technique still has to be established. We performed a continuous spinal anesthesia in a patient with Steinert's disease undergoing laparoscopic cholecystectomy using 10 mg of bupivacaine 0.5% and provided ventilatory support in the perioperative period. Continuous spinal anesthesia was safely used in Steinert's disease patients but is not described for laparoscopic cholecystectomy. We reported a continuous spinal anesthesia as an appropriate technique for laparoscopic cholecystectomy and particularly valuable in Steinert's disease patients.

RESUMO A doença de Steinert é uma desordem intrínseca do músculo com manifestações multissistêmicas. A miotonia pode afetar qualquer grupo muscular e é provocada por vários fatores e medicamentos usados em anestesia geral, como hipnóticos, sedativos e opiáceos. Embora alguns autores recomendem o uso de anestesia regional ou anestesia combinada com opiáceos em doses baixas, a técnica anestésica mais segura ainda precisa ser estabelecida. Administramos raquianestesia contínua em um paciente com doença de Steinert submetido à colecistectomia laparoscópica, com 10 mg de bupivacaína a 0,5%, e fornecemos suporte ventilatório no período perioperatório. A raquianestesia contínua foi usada com segurança em pacientes com doença de Steinert, mas não foi relatada em colecistectomia laparoscópica. Relatamos a raquianestesia contínua como uma técnica adequada para a colecistectomia laparoscópica e particularmente valiosa em pacientes com doença de Steinert.

Laparoscopic cholecystectomy under continuous spinal anesthesia in a patient with Steinert's disease.

Steinert's disease is an intrinsic disorder of the muscle with multisystem manifestations. Myotonia may affect any muscle group, is elicited by several factors and drugs used in general anesthesia like hypnotics, sedatives and opioids. Although some authors recommend the use of regional anesthesia or combined anesthesia with low doses of opioids, the safest anesthetic technique still has to be established. We performed a continuous spinal anesthesia in a patient with Steinert's disease undergoing laparoscopic cholecystectomy using 10mg of bupivacaine 0.5% and provided ventilatory support in the perioperative period. Continuous spinal anesthesia was safely used in Steinert's disease patients but is not described for laparoscopic cholecystectomy. We reported a continuous spinal anesthesia as an appropriate technique for laparoscopic cholecystectomy and particularly valuable in Steinert's disease patients.

Extensive regulation of nicotinate phosphoribosyltransferase (NAPRT) expression in human tissues and tumors.

Nicotinamide adenine dinucleotide (NAD) is a cofactor in redox reactions and a substrate for NAD-consuming enzymes, such as PARPs and sirtuins. As cancer cells have increased NAD requirements, the main NAD salvage enzymes in humans, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase (NAPRT), are involved in the development of novel anti-cancer therapies. Knowledge of the expression patterns of both genes in tissues and tumors is critical for the use of nicotinic acid (NA) as cytoprotective in therapies using NAMPT inhibitors. Herein, we provide a comprehensive study of NAPRT and NAMPT expression across human tissues and tumor cell lines. We show that both genes are widely expressed under normal conditions and describe the occurrence of novel NAPRT transcripts. Also, we explore some of the NAPRT gene expression mechanisms. Our findings underline that the efficiency of NA in treatments with NAMPT inhibitors is dependent on the knowledge of the expression profiles and regulation of both NAMPT and NAPRT.

Short-term outcome of patients with possible transient ischemic attacks: a prospective study.

BACKGROUND: Patients with transient ischemic attack (TIA) have an increased risk of vascular events. There is scarce data regarding the prognosis of patients with transient neurological symptoms less typical of TIA, in whom a vascular origin cannot be excluded, also known as possible TIA. In this study we aimed to compare the short-term prognosis between TIA and Possible TIA patients. METHODS: Patients with transient neurological events consecutively referred to a TIA Clinic during five years were classified as TIA, Possible TIA or mimic. Patients were prospectively followed. We compared the outcome at 30 and 90 days after TIA or Possible TIA. The primary outcome was stroke and the secondary outcome was a combination of vascular events (stroke, TIA, myocardial infarction or vascular death). RESULTS: Two hundred and fifty eight TIA and 109 Possible TIA patients were included. Possible TIA patients had no stroke 30 and 90 days after the event. In contrast, 3.1 % and 4 % of TIA patients had stroke at the same time points. Combined vascular events occurred in 1.9 % of Possible TIA (myocardial infarction) and 9.8 % of TIA patients (stroke and TIA) after 30 days (OR = 0.18, 95 % CI 0.04 to 0.76, P = 0.02); and in 1.9 % of Possible TIA patients (myocardial infarction) and 11.3 % of TIA patients (stroke and TIA) after 90 days (OR = 0.16, 95 % CI 0.04 to 0.67, P = 0.012). CONCLUSIONS: In this exploratory study, Possible TIA patients had less short-term vascular events than TIA patients.

A dietary-driven redox modulation of gut microbiome-host interactions: the rescue of epithelial barrier and mucus production during dysbiosis by dietary nitrate.

Dietary nitrate, from green-leafy vegetables, is reduced to nitrite in the oral cavity and to nitric oxide ((•)NO) in the stomach. Gut microbiota is raising a great deal of interest since it has been recognized to be crucial to maintain gastrointestinal (GI) and systemic welfare. Dysbiosis (altered gut flora) is associated with increased epithelial permeability, deficient mucus production and with the activation of inflammatory pathways. Here we investigate whether dietary nitrate rescues GI physiology during dysbiosis. Four groups of Wistar rats were maintained in the animal facilities for 7 days during which, in addition to food, they had access to 1) water, 2) an antibiotic cocktail (neomycin, bacitracin, imipenem), 3) antibiotic cocktail sodium nitrate 10mM, 4) sodium nitrate. Animals were weighted daily. At the end of 7(th) day they were anesthetized (isoflurane) and euthanized. Ceca were collected and weighted. The stomach was isolated and occludin, claudin-5, ZO-1, iNOS and myeloperoxidase (MPO) were analyzed by western blot and immunofluorescence (n=4, triplicate). Values are mean±SEM. Antibiotic exposure prevented weight gain in all animals when compared to controls. Nitrate prevented body weight loss under dysbiosis. Ceca from animals with altered gut flora contained more fecal material than the ones from animals treated with nitrate under the same circumstances (18.47±0.99g vs 14.7±71.12g, p<0.05). Dysbiosis reduced occludin expression but supplementation with nitrate recovered this protein to control levels (p<0.05). No significant differences were observed for ZO-1 or claudin-5. Nitrate prevented MPO (115.70±5.36 vs 61.00±19.00, p<0.05; % of control) and iNOS (279.8±88.1 vs 57.3±18.4, p<0.05, % of control) overexpression under dysbiosis suggesting the prevention of an over stimulated inflammatory status in the gut. This data suggests that dietary nitrate may ensure gastric epithelial integrity and mucus production during dysbiosis. Supported by PTDC/AGR-ALI/115744/2009.

Effect of diabetes/hyperglycemia on the rat retinal adenosinergic system.

The early stages of diabetic retinopathy (DR) are characterized by alterations similar to neurodegenerative and inflammatory conditions such as increased neural apoptosis, microglial cell activation and amplified production of pro-inflammatory cytokines. Adenosine regulates several physiological functions by stimulating four subtypes of receptors, A1AR, A2AAR, A2BAR, and A3AR. Although the adenosinergic signaling system is affected by diabetes in several tissues, it is unknown whether diabetic conditions in the retina can also affect it. Adenosine delivers potent suppressive effects on virtually all cells of the immune system, but its potential role in the context of DR has yet to be studied in full. In this study, we used primary mixed cultures of rat retinal cells exposed to high glucose conditions, to mimic hyperglycemia, and a streptozotocin rat model of type 1 diabetes to determine the effect diabetes/hyperglycemia have on the expression and protein levels of adenosine receptors and of the enzymes adenosine deaminase and adenosine kinase. We found elevated mRNA and protein levels of A1AR and A2AAR, in retinal cell cultures under high glucose conditions and a transient increase in the levels of the same receptors in diabetic retinas. Adenosine deaminase and adenosine kinase expression and protein levels showed a significant decrease in diabetic retinas 30 days after diabetes induction. An enzymatic assay performed in retinal cell cultures revealed a marked decrease in the activity of adenosine deaminase under high glucose conditions. We also found an increase in extracellular adenosine levels accompanied by a decrease in intracellular levels when retinal cells were subjected to high glucose conditions. In conclusion, this study shows that several components of the retinal adenosinergic system are affected by diabetes and high glucose conditions, and the modulation observed may uncover a possible mechanism for the alleviation of the inflammatory and excitotoxic conditions observed in diabetic retinas.