Validity of central pain processing biomarkers for predicting the occurrence of oncological chronic pain: a study protocol.

BACKGROUND: Despite recent improvements in cancer detection and survival rates, managing cancer-related pain remains a significant challenge. Compared to neuropathic and inflammatory pain conditions, cancer pain mechanisms are poorly understood, despite pain being one of the most feared symptoms by cancer patients and significantly impairing their quality of life, daily activities, and social interactions. The objective of this work was to select a panel of biomarkers of central pain processing and modulation and assess their ability to predict chronic pain in patients with cancer using predictive artificial intelligence (AI) algorithms. METHODS: We will perform a prospective longitudinal cohort, multicentric study involving 450 patients with a recent cancer diagnosis. These patients will undergo an in-person assessment at three different time points: pretreatment, 6 months, and 12 months after the first visit. All patients will be assessed through demographic and clinical questionnaires and self-report measures, quantitative sensory testing (QST), and electroencephalography (EEG) evaluations. We will select the variables that best predict the future occurrence of pain using a comprehensive approach that includes clinical, psychosocial, and neurophysiological variables. DISCUSSION: This study aimed to provide evidence regarding the links between poor pain modulation mechanisms at precancer treatment in patients who will later develop chronic pain and to clarify the role of treatment modality (modulated by age, sex and type of cancer) on pain. As a final output, we expect to develop a predictive tool based on AI that can contribute to the anticipation of the future occurrence of pain and help in therapeutic decision making.

Clinical and genetic factors involved in Porto-sinusoidal vascular disorder after oxaliplatin exposure.

BACKGROUND AND AIMS: Oxaliplatin (OX) has been described as a potential etiologic agent for porto-sinusoidal vascular disorder (PSVD). Our aim was to describe the natural history of PSVD due to OX in colon cancer (CRC) and identify risk factors for its development. METHODS: We made a multicenter retrospective case-control (ratio 1:3) study with patients diagnosed of PSVD-OX. Baseline data, end of treatment, years of follow-up and diagnosis of PSVD were collected and compared to controls (without PSVD). Besides, 16 different SNPs were selected from bibliography and analyzed by genotyping in the case group to identify potential genetic risk factors. RESULTS: 41 cases were identified, with a median time to PSVD diagnosis after the end of OX of 34 months. Spleen diameter was the strongest predictor of PSVD during treatment (OR 43.94 (14.48-133.336); p < 0.0001). Additionally, thrombocytopenia (<150 × 10^9) at one year was a significant disease risk marker (OR 9.35; 95% CI: 3.71-23.58; p = 0.001). We could not establish any significant association between the selected SNPs and PSVD diagnosis. CONCLUSION: The increase of spleen diameter is the strongest predictor of PSVD in patients treated with OX for CRC. These patients could be candidates for a specific follow-up of portal hypertension-related complications.

Conditioned pain modulation (CPM) paradigm type affects its sensitivity as a biomarker of fibromyalgia.

Fibromyalgia (FM) is a widespread chronic pain syndrome, possibly associated with the presence of central dysfunction in descending pain inhibition pathways. Conditioned Pain Modulation (CPM) has been proposed as a biomarker of FM. Nonetheless, the wide variety of methods used to measure CPM has hampered robust conclusions being reached. To clarify the validity of CPM as a biomarker of FM, we tested two CPM paradigms (parallel and sequential) in a sample of 23 female patients and 23 healthy women by applying test (mechanical) stimuli and conditioning (pressure cuff) stimuli. We evaluated whether CPM indices could correctly classify patients and controls, and we also determined the correlations between the indices and clinical variables such as symptomatology, disease impact, depression, quality of life, pain intensity, pain interference, fatigue and numbness. In addition, we compared the clinical status of CPM responders (efficient pain inhibitory mechanism) and non-responders. We observed that only parallel CPM testing correctly classified about 70% of patients with FM. In addition, more than 80% of healthy participants were found to be responders, while the rate was about 50% in the FM patients. The sequential CPM test was not as sensitive, with a decrease of up to 40% in the response rate for both groups. On the other hand, we did not observe any correlation between CPM measures and clinical symptoms. In summary, our findings demonstrate the influence of the CPM paradigm used and confirm that CPM may be a useful marker to complement FM diagnosis. However, the findings also cast doubts on the sensitivity of CPM as a marker of pain severity in FM.

Evaluation of commercial doses of a feed additive and silymarin on broiler performance with and without CCl4-induced liver damage.

Improving productive performance is a daily challenge in the poultry industry. Developing cost-effective additives and strategies that improve performance in antibiotic-free poultry production is critical to maintaining productivity and efficiency. This study evaluates the influence of a commercially available phytogenic feed additive (CA-PFA, that comprises silymarin, betaine and curcumin extracts as main ingredients) and silymarin on commercial broilers' productive performance and liver function with and without carbon tetrachloride (CCl4)-induced liver damage. The experiment was conducted in a completely randomized design, with six treatments, eight replicates, and eight birds per replicate in 18 one-day-old male broilers (Cobb Vantress 500) each; under a 3 × 2 factorial arrangement (3 diets x 2 levels of CCl4, 0 and 1 mL/kg body weight orally). The experimental treatments included 3 diets, commercially recommended doses of CA-PFA (500 mg/kg of feed; this dose provides 70 mg/kg of silymarin, besides the other active ingredients included in the formulation), silymarin (250 mg/kg of feed, containing 28% of active ingredient; this dose provides 70 mg/kg of silymarin as active ingredient) and an additive-free basal diet as a control. A standard commercial silymarin was used as a reference due to its well-known and extensively studied hepatoprotective properties that can mitigate the negative effects of CCl4 in the liver. The data were analyzed as a 2-way ANOVA, and the means showing significant (P ≤ 0.05) differences were then compared using the Post-Hoc Tukey HSD test. No interaction was detected between factors. Exposure to CCl4 had a noticeable detrimental effect on alertness, productive performance, and liver function of broilers without a significant increase in mortality. Including CA-PFA in the diet improved productive performance compared to the basal diet from day 21 to the end of the trial, on day 42. While no influence in feed intake was detected for any treatment, CA-PFA improved body weight gain (BWG) and feed conversion ratio (FCR) significantly (P < 0.05) from day 21 to the end of the trial in healthy and CCl4-exposed birds. The results show that CA-PFA supplementation improves performance parameters in broilers with and without CCl4-induced liver damage, when compared to a basal diet and the addition of a standard commercial silymarin product.

A specific gut microbiota signature is associated with an enhanced GLP-1 and GLP-2 secretion and improved metabolic control in patients with type 2 diabetes after metabolic Roux-en-Y gastric bypass.

Objective: To determine changes in incretins, systemic inflammation, intestinal permeability and microbiome modifications 12 months after metabolic RYGB (mRYGB) in patients with type 2 diabetes (T2D) and their relationship with metabolic improvement. Materials and methods: Prospective single-center non-randomized controlled study, including patients with class II-III obesity and T2D undergoing mRYGB. At baseline and one year after surgery we performed body composition measurements, biochemical analysis, a meal tolerance test (MTT) and lipid test (LT) with determination of the area under the curve (AUC) for insulin, C-peptide, GLP-1, GLP-2, and fasting determinations of succinate, zonulin, IL-6 and study of gut microbiota. Results: Thirteen patients aged 52.6 ± 6.5 years, BMI 39.3 ± 1.4 kg/m2, HbA1c 7.62 ± 1.5% were evaluated. After mRYGB, zonulin decreased and an increase in AUC after MTT was observed for GLP-1 (pre 9371 ± 5973 vs post 15788 ± 8021 pM, P<0.05), GLP-2 (pre 732 ± 182 vs post 1190 ± 447 ng/ml, P<0.001) and C- peptide, as well as after LT. Species belonging to Streptococaceae, Akkermansiacea, Rickenellaceae, Sutterellaceae, Enterobacteriaceae, Oscillospiraceae, Veillonellaceae, Enterobacterales_uc, and Fusobacteriaceae families increased after intervention and correlated positively with AUC of GLP-1 and GLP-2, and negatively with glucose, HbA1c, triglycerides and adiposity markers. Clostridium perfringens and Roseburia sp. 40_7 behaved similarly. In contrast, some species belonging to Lachnospiraceae, Erysipelotricaceae, and Rumnicocaceae families decreased and showed opposite correlations. Higher initial C-peptide was the only predictor for T2D remission, which was achieved in 69% of patients. Conclusions: Patients with obesity and T2D submitted to mRYGB show an enhanced incretin response, a reduced gut permeability and a metabolic improvement, associated with a specific microbiota signature.

Racial and Ethnic Demographic Reporting in Phase 2 Proton Therapy Clinical Trials: A Review.

Purpose: Equitable inclusion of racial and ethnic participation in clinical trials is crucial to improving disparities in health care, especially for historically marginalized populations. Our study aims to describe the racial and ethnic demographics of patients enrolled in published phase 2 clinical trials involving proton therapy in the United States. Materials and Methods: Published manuscripts were identified in PubMed, Embase, World of Science, and Cochrane. Phase 2 trials evaluating proton therapy for US patients were included. For each article in the study, data were collected comprising authors, title, and publication year, and clinical trial numbers were verified. Additional data included tumor site, primary institution, sample size, reported race/ethnicity, and raw number/percentile of race/ethnicity. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were used. Results: Overall, 970 titles were identified; 636 remained after duplicate screening, and 75 full-text articles were assessed. We identified 38 eligible manuscripts for inclusion comprising 2648 patients. Only 15 (39%) of the publications reported race/ethnicity. Of these, 8 (21%) and 10 (26%) documented Hispanic or Black trial participants, respectively; however, only 6 (16%) documented trial participation for both Hispanic and Black patients. Of the 1409 patients with a documented race/ethnicity, 89.0% (n = 1254) were non-Hispanic white, 5.3% (n = 75) were Black, and 2.2% (n = 31) were Hispanic. Other and unknown race/ethnicity comprised the remaining patients (3.5%; n = 49). Conclusion: We identified underreporting of demographic data in published phase 2 proton therapy trials, which unfortunately mirrored underreporting for cancer drug clinical trials. We also noted dramatic Black and Hispanic patient underrepresentation across the trials in which race and ethnicity are reported. Findings highlight the urgent need to identify and address barriers to proton therapy trials for Black and Hispanic patients ensuring clinical trials in radiation oncology are representative of the patients seen in clinical practice.

Increased STAT3 Activation in Periodontitis Drives Inflammatory Bone Loss.

Periodontitis is one of the most prevalent human inflammatory diseases. It is characterized by periodontal tissue destruction, progressively driven by the host response. In this regard, cytokines associated with tissue destruction, such as interleukin (IL)-6 and IL-23, use a common signaling pathway mediated by STAT3. This transcription factor is also needed for IL-17A production, a key mediator in periodontitis pathogenesis. Although several studies have reported increased activation of STAT3 in experimental periodontitis, a detailed characterization of STAT3 activation in human gingival tissues and its involvement in alveolar bone loss has yet to be explored. Using a cross-sectional study design, we detected increased proportions of pSTAT3-positive cells during periodontitis compared with health, particularly in epithelial cells and T cells. Other cell types of hematopoietic and nonhematopoietic origin also display STAT3 activation in gingival tissues. We detected increased STAT3 phosphorylation and expression of STAT3-related genes during experimental periodontitis. Next, we evaluated the role of STAT3 in alveolar bone destruction using a mouse model of STAT3 loss of function (mut-Stat3 mice). Compared with controls, mut-Stat3 mice had reduced alveolar bone loss following ligature-induced periodontitis. We also evaluated pharmacologic inhibition of STAT3 in ligature-induced periodontitis. Like mut-Stat3 mice, mice treated with STAT3 small-molecule inhibitor had reduced bone loss compared with controls. Our results demonstrate that STAT3 activation is increased in epithelial and T cells during periodontitis and indicate a pathogenic role of STAT3 in inflammatory alveolar bone loss.

Prevalence of ocular findings and their association with glycemia in dogs with diabetes mellitus: A 10-year clinical study (2009-2019).

Background: Although ocular findings in diabetic patients are well described, prevalence data for those is unknown. Aim: To describe the prevalence of ocular findings and their association with glycemia in dogs with diabetes mellitus. Methods: Medical records from diabetic dogs assessed by the ophthalmology and the internal medicine services at the Veterinary Teaching Hospital of the Autonomous University of Barcelona were reviewed (2009-2019). Results: Seventy-five dogs (150 eyes) of both genders (51/75 females; 68% and 24/75 males; 32%) and a mean age of 9.37 ± 2.43 years, were included. The most common ocular findings were cataracts (146/150; 97.3%), vitreous degeneration (45/98; 45.9%), anterior uveitis (47/150; 31.3%), aqueous deficiency dry eye (ADDE) (33/150; 22%), diffuse corneal edema (31/150; 20.7%), non-proliferative retinopathy (13/98; 13.3%), and lipid keratopathy (9/150; 6%). The most prevalent type of cataracts observed (78/146; 53.4%) was intumescent, which was commonly accompanied by non-proliferative retinopathy (p = 0.003). Among the diabetic dogs, blood glucose levels were statistically higher in dogs with non-proliferative retinopathy or anterior uveitis (p < 0.005). Conclusions: Ocular complications of diabetes mellitus in dogs are numerous, being the most frequent intumescent cataracts, vitreous degeneration, anterior uveitis, ADDE, diffuse corneal edema, and non-proliferative retinopathy. This high prevalence warrants a more detailed ophthalmic evaluation in diabetic dogs especially for those undergoing cataract surgery. Furthermore, a predisposition for anterior segment inflammation and non-proliferative retinopathy is suggested when fasting plasma glucose is higher than 600 mg/dl..

Protective effects of the succinate/SUCNR1 axis on damaged hepatocytes in NAFLD.

OBJECTIVE: Succinate and succinate receptor 1 (SUCNR1) are linked to fibrotic remodeling in models of non-alcoholic fatty liver disease (NAFLD), but whether they have roles beyond the activation of hepatic stellate cells remains unexplored. We investigated the succinate/SUCNR1 axis in the context of NAFLD specifically in hepatocytes. METHODS: We studied the phenotype of wild-type and Sucnr1-/- mice fed a choline-deficient high-fat diet to induce non-alcoholic steatohepatitis (NASH), and explored the function of SUCNR1 in murine primary hepatocytes and human HepG2 cells treated with palmitic acid. Lastly, plasma succinate and hepatic SUCNR1 expression were analyzed in four independent cohorts of patients in different NAFLD stages. RESULTS: Sucnr1 was upregulated in murine liver and primary hepatocytes in response to diet-induced NASH. Sucnr1 deficiency provoked both beneficial (reduced fibrosis and endoplasmic reticulum stress) and detrimental (exacerbated steatosis and inflammation and reduced glycogen content) effects in the liver, and disrupted glucose homeostasis. Studies in vitro revealed that hepatocyte injury increased Sucnr1 expression, which when activated improved lipid and glycogen homeostasis in damaged hepatocytes. In humans, SUCNR1 expression was a good determinant of NAFLD progression to advanced stages. In a population at risk of NAFLD, circulating succinate was elevated in patients with a fatty liver index (FLI) ≥60. Indeed, succinate had good predictive value for steatosis diagnosed by FLI, and improved the prediction of moderate/severe steatosis through biopsy when added to an FLI algorithm. CONCLUSIONS: We identify hepatocytes as target cells of extracellular succinate during NAFLD progression and uncover a hitherto unknown function for SUCNR1 as a regulator of hepatocyte glucose and lipid metabolism. Our clinical data highlight the potential of succinate and hepatic SUCNR1 expression as markers to diagnose fatty liver and NASH, respectively.

Avances en tuberculosis en el 54° Congreso Chileno de enfermedades respiratorias. 3a parte: Prevención de la tuberculosis activa mediante el tratamiento de la tuberculosis latente / Advances in tuberculosis at the 54th Chilean Congress of Respiratory Diseases. Part 3: prevention of active tuberculosis by treating latent tuberculosis

La infección tuberculosa latente (ITL) es un estado asintomático de la infección por Mycobacterium tuberculosis incapaz de transmitir la infección a otros, pero con el potencial de originar una tuberculosis (TBC) activa en el infectado, especialmente ante la presencia de factores de riesgo inmunológico. Es importante en personas de riesgo de desarrollar TBC reconocer la ITL utilizando test como la reacción a la tuberculina (PPD o TST) y los ensayos de liberación de Interferón-γ (IGRAs). Sin embargo, estos tests tienen limitaciones en su capacidad de predicción de riesgo de evolución de infección a enfermedad lo que conlleva a tener que tratar muchas personas para evitar algún caso de enfermedad. Nuevos tests se encuentran en desarrollo para mejorar la sensibilidad de reconocimiento de la ITL, distinguir infecciones recientes (que tienen el mayor riesgo de progresión a enfermedad) e incluso con la capacidad de detectar enfermedad subclínica o inicial. Para reducir la probabilidad de enfermar por TBC se utilizan tratamientos preventivos con fármacos, pero la cobertura mundial de esta terapia es reducida y la adherencia a terapias auto-administradas, como en el caso del uso de isoniazida diaria oral, es también baja. Otro problema de esta terapia son los riesgos de reacciones adversas (hepatitis, erupciones cutáneas) aunque no frecuentes. La recomendación de terapia actual de la ITL incluye el uso de rifamicinas y sus derivados. La asociación de isoniazida con rifapentina en una dosis semanal durante tres meses, administrada bajo supervisión, es la terapia de primera línea para mayores de 2 años, mostrando menos riesgo de hepatotoxicidad y mayor adherencia.

Latent Tuberculosis infection (LTBI) is the asymptomatic state of infection caused by Mycobacterium tuberculosis. Although untransmissible, LTBI can progress to active tuberculosis (TB), especially in people with immune risk factors. It is important to recognize LTBI in people at risk of developing TB; tuberculin skin test (PPD or TST) or interferon-γ release assays (IGRAs) are current diagnostic tests. However, these tests have limitations in their ability to predict subjects who will evolve from infection to disease; consequently, a large number of people with LTBI need treatment to avoid a reduced number of future TB disease cases. Newer tests are under development to improve the sensitivity in recognizing LTBI, distinguish recent infections with highest risk of progression to disease, and even be able to detect initial subclinical disease. Antimicrobial preventive treatment effectively reduces the probability of getting sick with TB, but worldwide availability of TB preventive therapy is limited, and adherence to self-administered therapies, as in the case of the use of daily oral isoniazid, is low. Adverse reactions risk (hepatitis, skin rash) although infrequent, is another problem with these therapies. Currently, LTBI management guidelines include regimens with use of rifamycins and their derivatives. The combination of isoniazid and rifapentine in a weekly dose for three months administered under supervision is the first line choice for LTBI therapy in those over 2 years of age, showing less hepatoxicity risk and greater adherence.

Avances en tuberculosis en el 54º congreso chileno de enfermedades respiratorias. 2ª parte: nuevas normas técnicas chilenas para el control y eliminación de la tuberculosis / New Chilean technical standards for the control and elimination of tuberculosis

La incidencia de la tuberculosis (TBC) en Chile se ha ido incrementando en el último quinquenio, excepto al inicio de la pandemia de Covid-19, donde la pesquisa de TBC se redujo en forma importante. El escenario epidemiológico actual dista del objetivo propuesto en la Estrategia Nacional de Salud (ENS) de la década 2011-2020 (un plan nacional de gobierno para enfermedades relevantes en la población) que consistía en alcanzar una tasa de incidencia de todas las formas de TBC menor a 5 / 100.000 habitantes. La nueva ENS para la década 2021-2030 propone reducir la incidencia de la enfermedad mediante el diagnóstico oportuno y precoz focalizando las intervenciones en las poblaciones de riesgo de la enfermedad (grupos vulnerables), a modo de pesquisa activa y no solo como pesquisa por consultas espontáneas de sintomáticos respiratorios, o tamizajes masivos que pueden no seleccionar a la población de riesgo. También propone intervenir en la prevención priorizando el estudio y tratamiento de la población con Infección Tuberculosa Latente (ITL) de mayor riesgo de progresión hacia la enfermedad. Por último, se pretende mejorar la eficiencia del proceso de tratamiento de la TBC, optimizando el acceso y adherencia a las terapias de los casos activos de TBC como medida de incrementar la proporción de curación. Una nueva norma ministerial para el manejo y control de la TBC puede ayudar enormemente a esta propuesta. Esta norma entrada plenamente en vigencia el año 2022 entrega las herramientas operacionales para cumplir el objetivo señalado para la nueva ENS. La norma incorpora actividades tendientes a lograr una mayor cobertura de estudio y tratamiento de la ITL en grupos específicos, donde se incluyen, además de los contactos infantiles, a los contactos adultos y a otros grupos vulnerables. La terapia para esta condición se realizará utilizando la asociación de Isoniazida con Rifapentina de preferencia. Esta terapia se aplica bajo supervisión en una dosis semanal durante 3 meses (12 dosis) y ha demostrado mejor adherencia y menor toxicidad hepática. Para el diagnóstico oportuno de TBC la pesquisa se ha focalizado en los sintomáticos respiratorios (tos con expectoración) de más de 2 semanas en personas que pertenecen a alguno de los grupos vulnerables, o que tienen rasgos clínicos muy sugerentes de la enfermedad (fiebre, sudoración vespertina, hemoptisis, compromiso del estado general). Como herramienta diagnóstica deja de utilizarse la baciloscopía por su baja sensibilidad y es sustituida por pruebas moleculares, siendo la plataforma automatizada de amplificación de ADN del complejo M. tuberculosis más utilizada y disponible en los servicios de salud públicos el GeneXpert MTB/RIF Ultra, que además entrega información de la susceptibilidad a la rifampicina a través de la identificación de una mutación específica del genoma (gen rpoB). Con esta tecnología se agiliza el proceso diagnóstico (puede obtener resultados durante el día de ejecución, habitualmente no demoraría más de 2 horas) y es de alta sensibilidad (sensibilidad muy similar al cultivo). El tratamiento de la TBC sensible a los fármacos del esquema primario (rifampicina = R, isoniazida = H, etambutol = E y pirazinamida = Z) consiste en la administración diaria en la fase inicial (con los 4 fármacos) durante 2 meses y en la fase de continuación (con isoniazida y rifampicina) durante 4 meses, totalmente supervisado. La TBC con resistencia a rifampicina tiene tratamiento con un esquema acortado oral de 9 meses con nuevos fármacos: bedaquilina, linezolid, clofazimina y levofloxacino (6 meses con los 4 fármacos, seguido de 3 meses con clofazimina y levofloxacino). Estas terapias de alta calidad son seguras y prometen mejores resultados de curación. La nueva norma significa una mayor cobertura para la erradicación de los reservorios de la enfermedad y una mayor precisión en el diagnóstico de las fuentes de trasmisión comunitaria de la enfermedad, siendo un aporte significativo hacia la eliminación de la TBC en el país.

The incidence of tuberculosis (TB) in Chile has been increasing in the last five years except at the beginning of the Covid-19 pandemic where TB screening has clearly decreased. The current epidemiological scenario is far from the goal proposed in the National Health Strategy (NHS) of the decade 2011-2020 (a national government plan for relevant diseases in the population) which was to achieve an incidence rate of all forms of TB less than 5/100,000 inhabitants. The new NHS for the decade 2021-2030 proposes to reduce the incidence of the disease through timely and early diagnosis by focusing interventions on populations at risk of the disease (vulnerable groups), as an active screening and not only as screening for spontaneous consultations of respiratory symptomatic or mass screenings that may not select the population at risk. It also proposed to intervene in prevention prioritizing the study and treatment of the population with Latent Tuberculosis Infection (LTI) at higher risk of progression to the disease. Finally, it intends to improve the efficiency of the TB treatment process, optimizing access and adherence to therapies of active TB cases as a measure to increase the cure rate. A new ministerial standard for the management and control of TB can greatly help this proposal. This standard, fully effective in 2022, provides the operational tools to meet the objective set for the new NHS. The standard incorporates activities aimed at achieving greater coverage of study and treatment of LTI in specific groups, which include, in addition to child contacts, adult contacts and other vulnerable groups. Therapy for this condition will be performed using the combination of isoniazid with rifapentine preferably. Therapy is administered under supervision and patients receive therapy once a week for 12 doses for 3 months. This therapy has shown better adherence and lower liver toxicity. For the timely diagnosis of TB, case finding has focused on respiratory symptoms (cough and expectoration) for more than 2 weeks, in individuals that belong to one of the vulnerable groups, or that have additional clinical features very suggestive of the disease (fever, afternoon sweats, hemoptysis, compromise of the general condition). Smear sputum as a diagnostic tool is no longer used due to low sensitivity and it was replaced by molecular tests in automated platform for DNA amplification of the mycobacterium TB complex. The more used and available in public health services is GeneXpert MTB / RIF Ultra, which also provides information on susceptibility to rifampicin through the identification of a specific genome mutation (rpoB gene). With this technology, the diagnostic process is streamlined (you can obtain results during the day of execution, usually it would not take more than 2 hours) and sensitivity is high (sensitivity very similar to culture). Treatment of TB sensitive to first line drugs (rifampicin, isoniazid, ethambutol and pyrazinamide) consists of daily administration in the initial phase (with four drugs) for 2 months and in the continuation phase (with isoniazid and rifampicin) for 4 months, fully supervised. In rifampicin resistant TB, the treatment is a shortened oral regimen of 9 months with new drugs: bedaquiline, linezolid, clofazimine and levofloxacin (six months with four drugs, followed by three months with clofazimine and levofloxacin). These high-quality therapies are safe and promise better healing results. The new national standards mean a greater coverage for the eradication of the reservoirs of the disease and a greater precision in the diagnosis of the sources of community transmission of tuberculosis, being a significant contribution towards the path of control and elimination of TB in the country.

Avances en tuberculosis en el 54° congreso chileno de enfermedades respiratorias. 1ra parte: nuevos esquemas acortados para tuberculosis drogoresistente ¿son adecuados para todos? / New shortened schemes for drug-resistant tuberculosis: are they suitable for everyone?

En esta presentación se realiza un recorrido a través de los diferentes esquemas terapéuticos de la tuberculosis drogo-resistente. Se muestra como los investigadores utilizan los nuevos fármacos disponibles y desarrollan diferentes esquemas cada vez más acortados y de administración por vía oral exclusiva, con la intención de lograr una mayor eficacia de curación de la tuberculosis resistente, con menos efectos colaterales y menor letalidad. La búsqueda de esquemas con una duración similar a las terapias de casos sensibles de tuberculosis (esquemas primarios de 6 meses) es el objetivo principal. Las pruebas moleculares como el Xpert ayudan enormemente a seleccionar los esquemas de terapia, según el perfil de susceptibilidad de los casos (resistencia a isoniazida, rifampicina, fluorquinolonas y combinaciones). Las terapias actuales de la tuberculosis drogo-resistente se basan en nuevos fármacos como fluorquinolonas, bedaquilina y linezolid, pero otros fármacos como pretomanid y delamanid también están siendo recomendados.

This presentation takes a tour through the different therapeutic schemes of drug-resistant tuberculosis. It shows how researchers use the new drugs available and develop different increasingly shortened schedules and exclusive oral administration, with the intention of achieving greater efficacy in curing resistant tuberculosis, with fewer side effects and lower lethality. The search for regimens with a duration similar to therapies of sensitive cases of tuberculosis (primary regimens of 6 months) is the main objective. Molecular tests, such as Xpert, greatly help in selecting therapy regimens, according to the susceptibility profile of the cases (resistance to isoniazid, rifampicin, fluorquinolones and combinations). Current drug-resistant tuberculosis therapies are based on new drugs such as fluorquinolones, bedaquiline and linezolid, but other drugs such as pretomanid and delamanid are also being recommended.

Multiparticulate Systems of Meloxicam for Colonic Administration in Cancer or Autoimmune Diseases.

The aim of this research is the development of new colonic release systems of meloxicam (MLX) a non-steroidal anti-inflammatory drug (NSAIDs) with pH and time-dependent vehicles for cancer or autoimmune diseases. The colon has a higher pH than the rest of the gastrointestinal tract (GIT) and this can be used as a modified release strategy. Eudragit® polymers are the most widely used synthetic products in the design of colonic release formulations because they might offer mucoadhesiveness and pH-dependent release. Colonic delivery systems produced with pH-dependent and permeable polymers (FS-30D) or with pH-independent and low permeability polymers (NM-30D), must dissolve at a pH range of 6.0-7.0 to delay the release of the drug and prevent degradation in the GIT, before reaching the colon. The conditions prepared to simulate a gastrointestinal transit showed the CNM multiparticulate system, composed of Eudragit® NM and cellulose, as the best release option for MLX with a more sustained release with respect to the other formulations. CNM formulation followed Higuchi and First-order release kinetics, thus MLX release was controlled by a combination of diffusion and polymers swelling/eroding processes.

Tuberculosis latente: diagnóstico y tratamiento actual / Latent tuberculosis: current diagnosis and treatment

Resumen La infección tuberculosa latente (TL) afecta al 23% de la población y constituye un reservorio de tuberculosis (TBC) ya que 10% progresa hacia una TBC. La TL se reconoce por pruebas como la tuberculina (PPD o TST) y los ensayos de liberación de Interferón gama (IGRAs). La sensibilidad de IGRAs (versión Quantiferon TB Gold plus) es 94% y del PPD 77%. La especificidad del Quantiferon TB Gold Plus es 97% y del PPD 68%. El valor predictivo de progresión a TBC activa de estas pruebas es bajo (PPD: 1,5%, IGRAs: 2,7%) pero mejora en personas de alto riesgo de contraer TBC (PPD: 2,4%, IGRAs: 6,8%). Las personas con pruebas negativas que posteriormente presentan viraje (prueba positiva) tienen mayor riesgo de progresión a TBC activa. Estas pruebas son útiles en el seguimiento de contactos intradomiciliarios, extranjeros de países con altas tasas de TBC, inmunosuprimidos, enfermedad renal crónica, diabetes, silicosis y secuelas pulmonares de TBC no tratada. En la terapia de TL se utiliza isoniazida (H) auto-administrada por plazos de 6 a 12 meses con eficacia protectora de 60% y riesgo de toxicidad hepática de 2% pero con baja adherencia (50-70%). La asociación de H con rifapentina en dosis única semanal durante 12 semanas tiene eficacia de 81%, adherencia de 82% y baja toxicidad hepática (0,4%). Nuevos biomarcadores de TL y vacunas que mejoren la inmunidad en TL se encuentran en estudio. El tratamiento de la TL puede reducir la incidencia de TBC a largo plazo.

Latent tuberculosis infection (LT) affects 23% of the population and constitutes a reservoir of tuberculosis (TB) as 10% progresses to TB. LT is recognized by tests such as tuberculin (PPD or TST) and Interferon gamma release assays (IGRAs). The sensitivity of IGRAs (Quantiferon TB Gold plus version) is 94% and PPD 77%. The specificity of Quantiferon TB Gold Plus is 97% and PPD 68%. The predictive value of progression to active TB of these tests is low (PPD: 1.5%, IGRAs: 2.7%) but improves in people at high risk of contracting TB (PPD: 2.4%, IGRAs: 6.8%). People with negative tests who subsequently turn around (positive) have a higher risk of progression to active TB. These tests are useful in the follow-up of intra-household contacts, foreigners from countries with high rates of TB, immunosuppressed, chronic kidney disease, diabetes, silicosis and pulmonary sequelae of untreated TB. In LT therapy, self-administered isoniazid (H) is used for periods from 6 to 12 months with protective efficacy of 60% and risk of liver toxicity of 2%, but with low adherence (50-70%). The association of H with rifapentine in a single weekly dose for 12 weeks has efficacy of 81%, adherence of 82% and low liver toxicity (0.4%). New LT biomarkers and vaccines that improve immunity in LT are under study. Treatment of LT may reduce the incidence of TB in the long term.

Relationship between surface dissolved iron inventories and net community production during a marine heatwave in the subarctic northeast Pacific.

From winter 2013-14 to the end of 2015-16, a high pressure atmospheric system induced elevated sea surface temperatures in the offshore subarctic northeast Pacific, resulting in a marine heatwave. Increased stratification due to the heatwave resulted in shoaling of the winter mixed layer and a decrease in nutrient re-supply to the euphotic zone. Here, we investigate relationships between dissolved iron (dFe) and macronutrients, net community production (NCP), (micro)nutrient uptake ratios, and phytoplankton community composition in the winter and summer from 2012 to 2015 to gain insight into coupled biogeochemical responses to the heatwave. Our investigation highlights the importance of external dFe supply during marine heatwave events, as a more shallow mixed layer reduces the transport of essential (micro)macronutrients to the surface layer. We conclude that recycled dFe did not contribute to NCP in 2014, but rather the vertical displacement of dFe rich water unrelated to mixed layer deepening played a major role. In 2015, such transport was not detected, resulting in abnormally low dFe and shift toward higher biomass of pico- and nano-phytoplankton size-classes.

Active and sham transcranial direct current stimulation (tDCS) improved quality of life in female patients with fibromyalgia.

PURPOSE: Fibromyalgia (FM) is a chronic pain syndrome with a strong impact on quality of life (QoL). Treatment of this condition remains a challenge, due to the scarce evidence for the effectiveness of the therapeutic approaches available. Current attention is focused on transcranial direct current stimulation (tDCS), which has yielded promising results for pain treatment. Rather than focusing only on pain relief, in this study, we aimed to determine how active or sham tDCS (over three cortical targets -the primary motor cortex, the dorsolateral prefrontal cortex and the operculo-insular cortex-) affect QoL in patients with FM. METHODS: Using a double-blind, placebo-controlled design, we applied fifteen tDCS sessions of 20' to initial 130 participants (randomized to any of the four treatment groups). We evaluated the QoL (assessed by SF-36) and the symptoms' impact (assessed by FIQ-R) in baseline, after treatment and at 6 months follow-up. RESULTS: All groups were comparable as regards age, medication pattern and severity of symptoms before the treatment. We found that QoL and symptoms' impact improved in all treatment groups (including the sham) and this improvement lasted for up to 6 months. However, we did not observe any group effect nor group*treatment interaction. CONCLUSIONS: After the intervention, we observed a non-specific effect that may be due to placebo, favoured by the expectations of tDCS efficacy and psychosocial variables inherent to the intervention (daily relationship with therapists and other patients in the clinic). Therefore, active tDCS is not superior to sham stimulation in improving QoL in FM.

Toward real applicability of electro-ozonizers: Paying attention to the gas phase using actual commercial PEM electrolyzers technology.

This work focuses on increasing the TRL of electro-ozonizer technology by evaluating the effect of electrolyte composition and operation conditions on the production of ozone, using an actual commercial cell, CONDIAPURE®, in conditions similar to what could be expected in a real application. Not only is attention paid to the changes in the concentration of ozone in the liquid phase, but also to those observed in the gas phase. The electrolyte and its recirculation flowrate, as well as operation temperatures and pressures are found to have significant influence on production rates. The most efficient way to produce ozone is operating at low temperatures and high pressures. In this work, 0.25 and 0.21 mg O3/min were obtained operating at 10 A in electrolytes consisting of aqueous solutions of perchloric and sulfuric acid, respectively, in tests carried out at 13 °C and 2 bars of gauge pressure. The negative effect of scavengers that appear electrochemically along the production of ozone is very important and seems to be partially compensated when organics are present in the solution due to the competition between the reaction of these scavengers with ozone or organics.