Personalizing Nutrition Strategies: Bridging Research and Public Health.

In recent years, although life expectancy has increased significantly, non-communicable diseases (NCDs) continue to pose a significant threat to the health of the global population. Therefore, eating habits have been recognized as key modifiable factors that influence people's health and well-being. For this reason, it is interesting to study dietary patterns, since the human diet is a complex mixture of macronutrients, micronutrients, and bioactive compounds, and can modulate multiple physiological processes, including immune function, the metabolism, and inflammation. To ensure that the data we acquired were current and relevant, we searched primary and secondary sources, including scientific journals, bibliographic indexes, and databases in the last 15 years with the most relevant articles. After this search, we observed that all the recent research on NCDs suggests that diet is a critical factor in shaping an individual's health outcomes. Thus, cardiovascular, metabolic, mental, dental, and visual health depends largely on the intake, habits and patterns, and nutritional behaviors. A diet high in processed and refined foods, added sugars, and saturated fats can increase the risk of developing chronic diseases. On the other hand, a diet rich in whole, nutrient-dense foods, such as vegetables, fruits, nuts, legumes, and a high adherence to Mediterranean diet can improve health's people.

Validation of Modaplex POLE mutation assay in endometrial carcinoma.

The TCGA-based molecular classification of endometrial cancer has emerged as an important tool to stratify patients according to prognosis. A simplified scheme has been proposed, by using immunohistochemistry for p53, MSH6, and PMS2 and a molecular test for POLE mutations (NGS or Sanger sequencing, techniques that are not available in many centers worldwide). In this study, we validate a novel method that allows simultaneous analysis of multiple pathogenic POLE mutations. The Modaplex technology integrates polymerase chain reaction and capillary electrophoresis. The design of this study encompassed 4 different steps: (1) a retrospective-pilot phase, with 80 tumors, balancing the four molecular subgroups. (2) A retrospective phase of 25 tumors obtained between 2016 and 2020, and 30 tumors obtained between 2000 and 2015. (3) An inter-laboratory corssavalidation step with 19 cases (belonging to phases 1 and 2). (4) A prospective cohort of 123 tumors, of unknown POLE status, with simultaneous validation by Sanger sequencing. A total of 258 samples were analyzed. In the first and second phases, the test showed positive/negative predictive values of 100%, by correctly identifying POLE mutation status in 79/79 and 55/55 cases. Phase 3 showed 100% of inter-laboratory consistency. Phase 4 showed 16 positive samples out of the 123 prospective cases. Overall, the test has revealed sensitivity and specificity of 100%, identifying a total of 47 POLE-mutated tumors. We have shown that this technique allows faster and easier identification of multiple pathogenic POLE mutations with high robustness and confidence when comparing to other tests such as Sanger sequencing.

Global Impacts of Western Diet and Its Effects on Metabolism and Health: A Narrative Review.

The Western diet is a modern dietary pattern characterized by high intakes of pre-packaged foods, refined grains, red meat, processed meat, high-sugar drinks, candy, sweets, fried foods, conventionally raised animal products, high-fat dairy products, and high-fructose products. The present review aims to describe the effect of the Western pattern diet on the metabolism, inflammation, and antioxidant status; the impact on gut microbiota and mitochondrial fitness; the effect of on cardiovascular health, mental health, and cancer; and the sanitary cost of the Western diet. To achieve this goal, a consensus critical review was conducted using primary sources, such as scientific articles, and secondary sources, including bibliographic indexes, databases, and web pages. Scopus, Embase, Science Direct, Sports Discuss, ResearchGate, and the Web of Science were used to complete the assignment. MeSH-compliant keywords such "Western diet", "inflammation", "metabolic health", "metabolic fitness", "heart disease", "cancer", "oxidative stress", "mental health", and "metabolism" were used. The following exclusion criteria were applied: (i) studies with inappropriate or irrelevant topics, not germane to the review's primary focus; (ii) Ph.D. dissertations, proceedings of conferences, and unpublished studies. This information will allow for a better comprehension of this nutritional behavior and its effect on an individual's metabolism and health, as well as the impact on national sanitary systems. Finally, practical applications derived from this information are made.

The Role of Adipokines in Health and Disease.

Adipokines are cell-signaling proteins secreted by adipose tissue that has been related to a low-grade state of inflammation and different pathologies. The present review aims to analyze the role of adipokines in health and disease in order to understand the important functions and effects of these cytokines. For this aim, the present review delves into the type of adipocytes and the cytokines produced, as well as their functions; the relations of adipokines in inflammation and different diseases such as cardiovascular, atherosclerosis, mental diseases, metabolic disorders, cancer, and eating behaviors; and finally, the role of microbiota, nutrition, and physical activity in adipokines is discussed. This information would allow for a better understanding of these important cytokines and their effects on body organisms.

Oxidative stress-induced FAK activation contributes to uterine serous carcinoma aggressiveness.

Uterine serous carcinoma (USC) is an aggressive form of endometrial cancer (EC), characterized by its high propensity for metastases. In fact, while endometrioid endometrial carcinoma (EEC), which accounts for 85% of EC, presents a good prognosis, USC is the most frequently fatal. Herein, we used for the first time a peptide-based tyrosine-kinase-activity profiling approach to quantify the changes in tyrosine kinase activation between USC and EEC. Among the tyrosine kinases highly activated in USC, we identified focal adhesion kinase (FAK). We conducted mechanistic studies using cellular models. In a USC cell line, targeting FAK either by inhibitors PF-573228 and defactinib (VS-6063) or by gene silencing limits 3D cell growth and reduces cell migration. Moreover, results from our studies suggest that oxidative stress is increased in USC tumors compared to EEC ones. Reactive oxygen species (ROS) induce tyrosine phosphorylation of FAK and a concomitant tyrosine phosphorylation of paxillin, a mediator of FAK signal transduction. Mechanistically, by tracking hundreds of individual cells per condition, we show that ROS increased cell distance and migration velocity, highlighting the role of ROS-FAK-PAX signaling in cell migration. Both defactinib and ROS scavenger N-acetylcysteine (NAC) revert this effect, pointing toward ROS as potential culprits for the increase in USC cell motility. A proof of concept of the role of FAK in controlling cell growth was obtained in in vivo experiments using cancer-tissue-originated spheroids (CTOS) and a patient-derived orthotopic xenograft model (orthoxenograft/PDOX). Defactinib reduces cell proliferation and protein oxidation, supporting a pro-tumoral antioxidant role of FAK, whereas antioxidant NAC reverts FAK inhibitor effects. Overall, our data points to ROS-mediated FAK activation in USC as being responsible for the poor prognosis of this tumor type and emphasize the potential of FAK inhibition for USC treatment.

Pediatric morbidity after oral surgery procedures under general anaesthesia: A systematic review.

The aim of this study is to carry out a systematic review of the existing literature on postoperative morbidity after general anaesthesia (GA) in the dental care of paediatric patients, its frequency, characteristics and association with the intervention performed. MATERIAL AND METHODS: An exhaustive search of the literature published up to 23 February 2022 was carried out in PubMed, Web of Science, Cochrane and EBSCO, with the following strategy: (infant OR child OR adolescent) AND (Oral Surgical Procedures OR Dentistry, Operative) AND Anesthesia, General AND Postoperative Complications. RESULTS: The most frequent reason for the indication of general anaesthesia was dental caries and its complications (up to 91.0% of patients), followed by lack of cooperation/anxiety and/or fear for dental procedures in the office (between 39.8 and 47.9%). There is a higher prevalence for treatments in the special patient group reaching 87.7% compared to 63.3% in healthy patients. The main comorbidities recorded were: physical or mental disability, neurological, haematological, cardiac disorders, asthma, Down's syndrome; it was not possible to establish their association with the intervention performed. Regarding complications, complaints occurred between 43.0 and 98.9% of cases within the first 24 hours, the main reason being pain (between 14.0% and 95.0%). CONCLUSIONS: Pediatric dental procedures under GA carry a very low risk of major complications, but have a virtually universal incidence of minor complications.

Importancia del estigma en epilepsia / Importance of Stigma in Epilepsy

Resumen El estigma es un fenómeno caracterizado por una respuesta negativa hacia una persona poseedora de un atributo diferente dentro del grupo social en el que se desarrolla. Se han descrito dos tipos de estigma: el percibido (sentido o interiorizado) y el promovido (social o promulgado). Dentro de las enfermedades con más carga asociada a estigma se encuentra la epilepsia, una de las enfermedades neurológicas más prevalentes a nivel mundial y de curso crónico. En los últimos años, se ha mostrado mayor interés en el estudio de este fenómeno, ya que afecta de manera directa la calidad de vida de las personas con epilepsia, influyendo en su desarrollo personal, escolar, laboral y pronóstico.

Abstract Stigma is a phenomenon characterized by a negative response to a person possessing a different attribute within the social group it develops. Two types of stigmas have been described: perceived (felt) and promoted (enacted). Among the diseases with the greatest burden associated with stigma is epilepsy, one of the most prevalent neurological diseases worldwide and with a chronic course. In recent years, greater interest has been shown in the study of this phenomenon since it directly affects the quality of life of people with epilepsy, influencing their personal, academic and work development and prognosis.

Comparison of the Idylla™ MSI assay with the Promega™ MSI Analysis System and immunohistochemistry on formalin-fixed paraffin-embedded tissue of endometrial carcinoma: results from an international, multicenter study.

Determination of microsatellite instability (MSI) and mismatch repair deficiency (MMRD), respectively, in endometrial carcinomas (ECs) is important for diagnostic and prognostic purposes, identification of Lynch syndrome carriers, and selection of patients for immunotherapy. The Idylla™ MSI assay is fully automated, does not require non-tumoral tissue, and can be performed in about 150 min. Two hundred forty-two formalin-fixed paraffin-embedded (FFPE) EC samples from 7 international centers were tested by the Idylla™ MSI assay and compared to the Promega™ MSI Analysis System and immunohistochemistry (IHC) for MMR proteins. The cases were selected with an enrichment of MSI EC to around 40%. Concordance was 87.5% between the Idylla™ MSI assay and IHC and 88.58% between IHC and Promega™ MSI assay. Concordance between Idylla™ and Promega™ MSI assays was 89.91%. Discordant results occurred more frequently in cases with MSH6 or PMS2 deficiency. Invalid cases occurred with the three techniques (IHC, 7.00%; Promega™ MSI assay, 5.37%; and Idylla™ MSI assay, 2.47%). The concordance rate between Idylla™ MSI assay and the other 2 methods increased to 88.83% for IHC and to 91.22% for the Promega™ MSI assay when the cutoff of instability in the scoring system was moved from 0.5 to 0.3. The Idylla™ MSI assay is a rapid and highly concordant test for MSI in EC. Modification of the Idylla™ scoring system could increase the sensitivity and specificity of the MSI assay for EC analysis.

Physical activity and COVID-19. The basis for an efficient intervention in times of COVID-19 pandemic.

The Coronavirus Disease 2019 (COVID-19) pandemic has shocked world health authorities generating a global health crisis. The present study aimed to analyze the different factors associated with physical activity that could have an impact in the COVID-19, providing a practical recommendation based on actual scientific knowledge. We conducted a consensus critical review using primary sources, scientific articles, and secondary bibliographic indexes, databases, and web pages. The method was a narrative literature review of the available literature regarding physical activity and physical activity related factors during the COVID-19 pandemic. The main online database used in the present research were PubMed, SciELO, and Google Scholar. COVID-19 has negatively influenced motor behavior, levels of regular exercise practice, eating and nutritional patterns, and the psychological status of citizens. These factors feed into each other, worsening COVID-19 symptoms, the risk of death from SARS-CoV-2, and the symptoms and effectiveness of the vaccine. The characteristics and symptoms related with the actual COVID-19 pandemic made the physical activity interventions a valuable prevention and treatment factor. Physical activity improves body composition, the cardiorespiratory, metabolic, and mental health of patients and enhancing antibody responses in vaccination.

Harassment of health professionals by the infant food industry at scientific events / Assédio da indústria de alimentos infantis a profissionais de saúde em eventos científicos

ABSTRACT OBJECTIVE To analyze the receipt of sponsorships from breast-milk substitute companies by health professionals in scientific events. METHODS Multicenter study (Multi-NBCAL) performed from November 2018 to November 2019 in six cities in different Brazilian regions. In 26 public and private hospitals, pediatricians, nutritionists, speech therapists, and a hospital manager were interviewed using a structured questionnaire. Descriptive analyses were carried out regarding the health professionals' knowledge about the Norma Brasileira de Comercialização de Alimentos para Lactentes e Crianças de Primeira Infância, Bicos, Chupetas e Mamadeiras (NBCAL - Brazilian Code of Marketing of Infant and Toddlers Food and Childcare-related Products), companies sponsoring scientific events, and material or financial sponsorships received, according to profession. RESULTS We interviewed 217 health professionals, mainly pediatricians (48.8%). Slightly more than half of the professionals (54.4%) knew NBCAL, most from Baby-friendly Hospitals. Most health professionals (85.7%) attended scientific events in the last two years, more than half of them (54.3%) sponsored by breast-milk substitute companies, especially Nestlé (85.1%) and Danone (65.3%). These professionals received sponsorships in the events, such as office supplies (49.5%), meals or invitations to parties (29.9%), promotional gifts (21.6%), payment of the conference registration fee (6.2%) or ticket to the conference (2.1%). CONCLUSION The infant food industries violate NBCAL by harassing health professionals in scientific conferences, offering diverse material and financial sponsorships.

RESUMO OBJETIVO Analisar o recebimento de patrocínios da indústria de substitutos do leite materno por profissionais de saúde em eventos científicos. MÉTODOS Inquérito multicêntrico (Multi-NBCAL) conduzido entre novembro de 2018 e novembro de 2019 em seis cidades de diferentes regiões brasileiras. Em 26 hospitais públicos e privados foram entrevistados pediatras, nutricionistas, fonoaudiólogos e um membro da chefia, mediante questionário estruturado. Foram realizadas análises descritivas do conhecimento dos profissionais de saúde sobre a Norma Brasileira de Comercialização de Alimentos para Lactentes e Crianças de Primeira Infância, Bicos, Chupetas e Mamadeiras (NBCAL), das empresas patrocinadoras de eventos científicos e dos patrocínios financeiros ou materiais recebidos, conforme a categoria profissional. RESULTADOS Foram entrevistados 217 profissionais de saúde, principalmente pediatras (48,8%). Pouco mais da metade dos profissionais (54,4%) afirmaram conhecer a NBCAL, principalmente em Hospitais Amigos da Criança. A maior parte (85,7%) dos profissionais de saúde havia participado de congressos científicos nos últimos dois anos, mais da metade, 54,3%, deles apoiados pela indústria de substitutos do leite materno, em especial pela Nestlé (85,1%) e Danone (65,3%). Patrocínios foram recebidos por esses profissionais nos eventos, como materiais de escritório (49,5%), refeições ou convites para festas (29,9%), brindes (21,6%), pagamento de inscrição (6,2%) ou de passagem para o congresso (2,1%). CONCLUSÃO As indústrias de alimentos infantis infringem a NBCAL ao assediar profissionais de saúde em congressos científicos, oferecendo patrocínios materiais e financeiros diversos.

Olfactory function in patients with temporal lobe epilepsy; correlation of functional magnetic resonance imaging for olfaction with the laterality of the epileptic focus.

The olfactory function shares the same cerebral structures as those involved in the origin and propagation of focal temporal lobe seizures. Likewise, functional magnetic resonance imaging (fMRI) allows the study of olfactory function. This suggests that by quantitatively studying the olfactory function with an olfactory paradigm through fMRI it is possible to identify the functional alteration produced by the epileptic focus. The objective of the present study was to assess the olfactory function in the side of the epileptic focus in patients with mesial temporal lobe epilepsy, using fMRI for smell, and propose a non-invasive diagnostic method for patients candidates to mesial temporal lobe epilepsy surgery. METHODS: Patients (n = 18) with clinical diagnosis of mesial temporal lobe epilepsy, refractory to pharmacological treatment: 7 patients (38.9%) with non-invasive studies consistent enough to submit them to anterior temporal lobectomy, and 11 (61.1%) patients where focal onset seizures were identified by stereoelectroencephalography (SEEG) on the left temporal lobe in 5 (27.8%) and in both temporal lobes in 2 (11.1%). Patients were evaluated using EEG, MRI, neuropsychological data, and fMRI with olfactory paradigm. Results of the fMRI were compared with the laterality of the epileptic focus determined by intracranial electroencephalogram recordings through stereotactically placed electrodes, and with post-surgical outcome at one year of follow-up. RESULTS: fMRI showed a lower olfactory activation in 81.8% concordant with unilateral onset seizures. There were significant differences of olfactory fMRI activation between epileptic and non-epileptic foci. CONCLUSION: Functional magnetic resonance imaging with an olfactory paradigm may be a non-invasive diagnostic tool to determine the laterality of seizure onset in the mesial temporal lobe.

Differential Immunoexpression of BRAF/V600E, Senescence Markers, PTEN, and T-type Calcium Channels in Acquired Naevi According to their Histopathological and Dermoscopic Classification.

BRAF/V600E mutation and other cell growth/growth-control mechanisms are involved in naevogenesis and melanomagenesis. Immunoexpression of BRAF/V600E and other molecules (p16, phosphatase and tensin homologue (PTEN), Ki67, hTERT and Cav3.1 and 3.2 calcium channels) were investigated in 80 histopatho-logically and dermoscopically classified acquired naevi. Regarding BRAF/V600E, dysplastic naevi showed lower immunostaining than common naevi, which was significant in comparison with intradermal naevi, which showed the highest BRAF/V600E histoscore. Junctional naevi showed the lowest BRAF/V600E levels. Globular/cobblestone and reticular dermoscopic patterns were consistently associated with high and low BRAF/V600E immunoexpression, respectively, but Zalaudek's peripheral globule pattern (CR/PG) showed the highest BRAF/V600E immunoexpression. Among global patterns, the previously not investigated multicomponent pattern showed the lowest BRAF/V600E immunoexpression. Regarding the remaining biomarkers, new immunohistochemical features were found, in particular p16 and PTEN low expression in multicomponent pattern; and Ki67, hTERT and Cav.3.1 high expression in CR/PG. In conclusion, histopathology and dermoscopy provide complementary information regarding the biology of melanocytic naevi.

BRAFV600E Mutant Allele Frequency (MAF) Influences Melanoma Clinicopathologic Characteristics.

BACKGROUND: Cutaneous melanoma shows high variability regarding clinicopathological presentation, evolution and prognosis. METHODS: Next generation sequencing was performed to analyze hotspot mutations in different areas of primary melanomas (MMp) and their paired metastases. Clinicopathological features were evaluated depending on the degree of variation of the BRAFV600E mutant allele frequency (MAF) in MMp. RESULTS: In our cohort of 14 superficial spreading, 10 nodular melanomas and 52 metastases, 17/24 (71%) melanomas had a BRAFV600E mutation and 5/24 (21%) had a NRASQ61 mutation. We observed a high variation of BRAFV600E MAF (H-BRAFV600E) in 7/17 (41%) MMp. The H-BRAFV600E MMp were all located on the trunk, had lower Breslow and mitotic indexes and predominantly, a first nodal metastasis. Regions with spindled tumor cells (Spin) and high lymphocytic infiltrate (HInf) were more frequent in the H-BRAFV600E patients (4/7; 57%), whereas regions with epithelial tumor cells (Epit) and low lymphocytic infiltrate (LInf) were predominant (6/10; 60%) and exclusive in the low BRAFV600E MAF variation tumors (L-BRAFV600E). The H-BRAFV600E/Spin/HInf MMp patients had better prognostic features and nodal first metastasis. CONCLUSIONS: The H-BRAFV600E MMp were located on the trunk, had better prognostic characteristics, such as lower Breslow and mitotic indexes as well as high lymphocytic infiltrate.

Factores psicosociales del personal de una organización educativa y su relación con desgaste psíquico / Psychosocial Factors in Workers of an Educational Organization and their Relationship with Psychic Exhaustion

Resumen. Objetivo. Evaluar los factores psicosociales percibidos por los trabajadores en una organización pública de educación superior y su relación con el desgaste psíquico. Método. La investigación fue transversal, participaron 292 trabajadores y se utilizó una batería que evalúa las dimensiones: Contexto de Trabajo, Contenido de Trabajo y Factores Individuales, como variables independientes y Desgaste Psíquico como variable dependiente. Resultados. La percepción de los participantes resultó favorable en más del 80%. Las dimensiones psicosociales indicaron una correlación media, positiva y estadísticamente significativa con el Desgaste Psíquico, consistente con los análisis Odds Ratio. Factores Individuales fue la dimensión de mayor influencia acorde con el modelo de regresión lineal múltiple, seguida de Contenido de Trabajo.

Abstract. Objective. To evaluate the psychosocial factors perceived by workers in a higher education public organization and their relationship with the psychic exhaustion. Method. Research was cross-sectional, 292 workers participated and it was used a test battery to evaluate the dimensions: Work Context, Work Content and Individual Factors, as independent variables and Psychic Exhaustion as a dependent variable. Results. Perception of the participants was favorable by more than 80%. Psychosocial dimensions indicated a medium, positive and statistically significant correlation with the Psychic Exhaustion, consistent with Odds Ratio analysis. Individual Factors was the dimension with the greatest influence according to the multiple linear regression model, followed by Work Content.

Multi-center real-world comparison of the fully automated Idylla™ microsatellite instability assay with routine molecular methods and immunohistochemistry on formalin-fixed paraffin-embedded tissue of colorectal cancer.

Microsatellite instability (MSI) is present in 15-20% of primary colorectal cancers. MSI status is assessed to detect Lynch syndrome, guide adjuvant chemotherapy, determine prognosis, and use as a companion test for checkpoint blockade inhibitors. Traditionally, MSI status is determined by immunohistochemistry or molecular methods. The Idylla™ MSI Assay is a fully automated molecular method (including automated result interpretation), using seven novel MSI biomarkers (ACVR2A, BTBD7, DIDO1, MRE11, RYR3, SEC31A, SULF2) and not requiring matched normal tissue. In this real-world global study, 44 clinical centers performed Idylla™ testing on a total of 1301 archived colorectal cancer formalin-fixed, paraffin-embedded (FFPE) tissue sections and compared Idylla™ results against available results from routine diagnostic testing in those sites. MSI mutations detected with the Idylla™ MSI Assay were equally distributed over the seven biomarkers, and 84.48% of the MSI-high samples had ≥ 5 mutated biomarkers, while 98.25% of the microsatellite-stable samples had zero mutated biomarkers. The concordance level between the Idylla™ MSI Assay and immunohistochemistry was 96.39% (988/1025); 17/37 discordant samples were found to be concordant when a third method was used. Compared with routine molecular methods, the concordance level was 98.01% (789/805); third-method analysis found concordance for 8/16 discordant samples. The failure rate of the Idylla™ MSI Assay (0.23%; 3/1301) was lower than that of referenced immunohistochemistry (4.37%; 47/1075) or molecular assays (0.86%; 7/812). In conclusion, lower failure rates and high concordance levels were found between the Idylla™ MSI Assay and routine tests.

Electrical Stimulation of Subiculum for the Treatment of Refractory Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis: A 2-Year Follow-Up Study.

INTRODUCTION: Evidence has been provided that the subiculum may play an important role in the generation of seizures. Electrical stimulation at this target has been reported to have anticonvulsive effects in kindling and pilocarpine rat models, while in a clinical study of hippocampal deep brain stimulation (DBS), contacts closest to the subiculum were associated with a better anticonvulsive effect. OBJECTIVES: To evaluate the effect of electrical stimulation of the subiculum in patients with refractory mesial temporal lobe epilepsy (MTLE) who have hippocampal sclerosis (HS). METHODS: Six patients with refractory MTLE and HS, who had focal impaired awareness seizures (FIAS) and focal to bilateral tonic-clonic seizures (FBTCS), had DBS electrodes implanted in the subiculum. During the first month after implantation, all patients were OFF stimulation, then they all completed an open-label follow-up of 24 months ON stimulation. DBS parameters were set at 3 V, 450 µs, 130 Hz, cycling stimulation 1 min ON, 4 min OFF. RESULTS: There was a mean reduction of 49.16% (±SD 41.65) in total seizure number (FIAS + FBTCS) and a mean reduction of 67.93% (±SD 33.33) in FBTCS at 24 months. FBTCS decreased significantly with respect to baseline, starting from month 2 ON stimulation. CONCLUSIONS: Subiculum stimulation is effective for FBTCS reduction in patients with MTLE and HS, suggesting that the subiculum mediates the generalization rather than the genesis of mesial temporal lobe seizures. Better results are observed at longer follow-up times.

Colitis Isquémica en Dolicomegacolon Andino

Resumen La colitis isquémica representa la forma más frecuente de isquemia intestinal ( 60-70%) como consecuencia de privación transitoria del flujo vascular por alteraciones anatómicas funcionales, locales o sistémicas. Se presenta el caso clínico de paciente de 70 años de edad procedente de La Paz Bolivia, ciudad a 3 650 m.s.n.m. a quien se diagnosticó colitis isquémica por torsión del eje mesentérico a nivel de colon sigmoides asociado a dolicomegacolon andino, procediendo a colectomía izquierda y anastomosis termino-terminal, con buena evolución.

Abstract Ischaemic colitis represents the most frequent form of intestinal ischaemia (60-70%) as a consequence of transient deprivation of vascular flow due to functional, local or systemic anatomical alterations. We present a case report of a 70-year-old patient from La Paz, Bolivia, a city at an altitude of 3 650 m.a.m.s.l., who was diagnosed with ischaemic colitis as a result of torsion of the mesenteric axis at the level of the sigmoid colon associated with Andean dolichomegacolon, followed by left colectomy and termino-terminal anastomosis, with satisfactory evolution.

Detection of somatic mutations in peritoneal lavages and plasma of endometrial cancer patients: A proof-of-concept study.

Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries. Although most patients are diagnosed at early stages, 15-20% will relapse despite local treatment. Presently, there are no reliable markers to identify patients with worse outcomes who may benefit from adjuvant treatments, such as chemotherapy, and liquid biopsies may be of use in this setting. Peritoneal lavages are systematically performed during endometrial surgery but little data are available about their potential as liquid biopsies. We analyzed KRAS and PIK3CA mutations in paired surgical biopsies, blood and cytology-negative peritoneal lavages in a cohort of 50 EC patients. Surgical biopsies were submitted to next-generation sequencing (NGS) while circulating-free DNA (cfDNA) purified from plasma and peritoneal lavages was analyzed for KRAS and PIK3CA hotspot mutations using a sensitive quantitative polymerase chain reaction (PCR) assay. NGS of biopsies revealed KRAS, PIK3CA or concomitant KRAS + PIK3CA mutations in 33/50 (66%) EC patients. Of those, 19 cases carried hotspot mutations. Quantitative PCR revealed KRAS and/or PIK3CA mutations in the lavages of 9/19 (47.4%) hotspot EC patients. In contrast, only 2/19 (10.5%) blood samples from hotspot EC patients were positive. Mutations found in cfDNA consistently matched those in paired biopsies. One of the two patients positive in plasma and lavage died in less than 6 months. In conclusion, mutational analysis in peritoneal lavages and blood from early stage EC is feasible. Further studies are warranted to determine if it might help to identify patients with worse prognosis. Human genes discussed: KRAS, KRAS proto-oncogene, GTPase; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha.

Cannabidiol Acts at 5-HT1A Receptors in the Human Brain: Relevance for Treating Temporal Lobe Epilepsy.

Experimental evidence indicates that cannabidiol (CBD) induces anxiolytic and antiepileptic effects through the activation of 5-HT1A receptors. These receptors are coupled to Gi/o proteins and induce inhibitory effects. At present, the interaction of CBD with 5-HT1A receptors in the human brain is unknown. The aim of this study focused on evaluating the interaction between CBD and 5-HT1A receptors in cell membranes obtained from the hippocampus and temporal neocortex of autopsies and patients with drug-resistant mesial temporal lobe epilepsy (DR-MTLE). Cell membranes were isolated from the hippocampus and temporal neocortex of a group of patients with DR-MTLE who were submitted to epilepsy surgery (n = 11) and from a group of autopsies (n = 11). The [3H]-8-OH-DPAT binding assay was used to determine the pharmacological interaction of CBD with 5-HT1A receptors. The [35S]-GTPγS assay was used to investigate the CBD-induced activation of Gi/o proteins through its action on 5-HT1A receptors.The CBD affinity (pK i) for 5-HT1A receptors was similar for autopsies and patients with DR-MTLE (hippocampus: 4.29 and 4.47, respectively; temporal neocortex: 4.67 and 4.74, respectively). Concerning the [35S]-GTPγS assay, no statistically significant changes were observed for both hippocampal and neocortical tissue (p > 0.05) at low CBD concentrations (1 pM to 10 µM). In contrast, at high concentrations (100 µM), CBD reduced the constitutive activity of Gi/o proteins of autopsies and DR-MTLE patients (hippocampus: 39.2% and 39.6%, respectively; temporal neocortex: 35.2% and 24.4%, respectively). These changes were partially reversed in the presence of WAY-100635, an antagonist of 5-HT1A receptors, in the autopsy group (hippocampus, 59.8%, p < 0.0001; temporal neocortex, 71.5%, p < 0.0001) and the group of patients with DR-MTLE (hippocampus, 53.7%, p < 0.0001; temporal neocortex, 68.5%, p < 0.001). Our results show that CBD interacts with human 5-HT1A receptors of the hippocampus and temporal neocortex. At low concentrations, the effect of CBD upon Gi/o protein activation is limited. However, at high concentrations, CBD acts as an inverse agonist of 5-HT1A receptors. This effect could modify neuronal excitation and epileptic seizures in patients with DR-MTLE.

Intratumour heterogeneity in endometrial serous carcinoma assessed by targeted sequencing and multiplex ligation-dependent probe amplification: a descriptive study.

AIMS: Endometrial serous carcinoma (ESC) represents the most aggressive subtype of endometrial carcinoma (EC). According to The Cancer Genome Atlas (TCGA), ESC exhibits a genomic profile characterised by frequent TP53 mutations and somatic copy-number alterations (SCNA). Several studies have suggested the role of intratumour heterogeneity (ITH) in tumour progression and therapy resistance, highlighting ITH as a challenge for personalised medicine. ITH is described as the co-existence of clonal and subclonal cellular populations within a single tumour. To date, the extent and prevalence of ITH in ESC have not been fully evaluated. The aim of this study was to address ITH analysis in ESC. We performed a descriptive integrated molecular approach using targeted sequencing and multiplex ligation-dependent probe amplification (MLPA) to identify mutations and SCNA patterns, respectively. METHODS AND RESULTS: Eight ESC were examined, selecting three tumour regions per case and their corresponding normal tissue. For targeted sequencing a gene panel of 40 genes based on TCGA and other survey data was performed. For MLPA different probe mixes were used to detect SCNA in 106 genes. Analysis of mutations and SCNA were performed in each sample and comparative analysis of the three tumour regions was also conducted. Targeted sequencing showed that mutations in TP53, PIK3CA and PPP2R1A were ubiquitous in all tumour regions. Moreover, MLPA results demonstrated a high frequency of SCNA, according to the already known presence of genomic instability in ESC. Unlike the homogeneous distribution of somatic mutations, SCNA exhibited ITH affecting targetable genes such as ERBB2. CONCLUSIONS: Our study suggests that somatic gene copy-number alterations are the main source of ITH in ESC.