Control hospitalario de la diabetes y de la hiperglucemia: una auditoría en hospitales españoles / Inpatient management of diabetes and hyperglycemia: an audit of Spanish hospitals

Objetivos Evaluación de la calidad de la asistencia a los pacientes con diabetes mellitus ingresados en España. Métodos Estudio transversal que incluyó a 1.193 (26,7%) pacientes con diabetes tipo 2 o hiperglucemia de un total de 4.468 pacientes ingresados en los servicios de medicina interna de 53 hospitales (España). Se recogieron datos demográficos, adecuación de la monitorización de la glucemia capilar, tratamiento administrado durante el ingreso y terapia recomendada al alta. Resultados La edad mediana fue de 80 años (74-87), 561 (47%) pacientes eran mujeres, con un índice de Charlson de 4 (2-6) puntos, siendo clasificados frágiles 742 (65%). La mediana de glucemia al ingreso fue de 155 (119-213) mg/dL. Al tercer día de ingreso el número de glucemias capilares en objetivo (80-180mg/dL) fue de 792/1.126 (70,3%) en el predesayuno, 601/1.083 (55,4%) en la precomida, 591/1.073 (55,0%) en la precena y 317/529 (59,9%) durante la noche. Se observó hipoglucemia en 35 (0,9%) pacientes. El tratamiento durante el ingreso fue realizado con insulina en escala móvil en 352 (40,5%) pacientes, insulina basal y análogos de insulina rápida en 434 (50%) y dieta exclusivamente en 101 (9,1%). Un total de 735 (61,6%) pacientes disponían de un valor reciente de HbA1c. En el alta se incrementó el uso de iSGLT2 (30,1 vs. 21,6%; p<0,001) y el uso de insulina basal (25,3 vs. 10,1%; p<0,001). Conclusiones Existe un excesivo uso de insulina en escala móvil, una deficiente información de los valores de HbA1c y una prescripción aún deficiente de tratamientos con beneficio cardiovascular al alta (AU)

Objectives Evaluation of the quality of care for patients with diabetes mellitus admitted to hospitals in Spain. Methods Cross-sectional study in one day that included 1193 (26.7%) patients with type 2 diabetes or hyperglycemia out of 4468 patients admitted to the internal medicine departments of 53 hospitals in Spain. We collected demographic data, adequacy of capillary glycemic monitoring, treatment administered during admission, and recommended therapy at discharge. Results The median age of the patients was 80 years (74-87), of which 561 (47%) were women, with a Charlson index of 4 points (2-6), and 742 (65%) were fragile. Median blood glucose on admission was 155mg/dL (119-213). On the third day, the number of capillary blood glucose levels in target (80-180mg/dL) was pre-breakfast 792/1126 (70.3%), pre-lunch 601/1083 (55.4%), pre-dinner 591/1073 (55.0%) and night 317/529 (59.9%). A total of 35 patients (0.9%) were suffering from hypoglycemia. Treatment during hospitalization was performed with sliding scale insulin in 352 (40.5%) patients, with basal insulin and rapid insulin analogs in 434 (50%), or with diet exclusively in 101 (9.1%). A total of 735 (61.6%) patients had a recent HbA1c value. At the time of discharge, the use of iSGLT2 increased significantly (30.1% vs. 21.6%; p<0.001), as well as the use of basal insulin (25.3% vs. 10.1%; p<0.001). Conclusions There is an excessive use of insulin on a sliding scale as well as deficient information on HbA1c values and an even deficient prescription at the discharge of treatments with cardiovascular benefit (AU)

Inpatient management of diabetes and hyperglycaemia: an audit of Spanish hospitals.

OBJECTIVES: Evaluation of quality of care for patients with diabetes mellitus admitted to hospitals in Spain. METHODS: Cross-sectional study in one day that included 1193 (26.7%) patients with type 2 diabetes or hyperglycaemia out of a total of 4468 patients admitted to the internal medicine departments of 53 hospitals in Spain. We collected demographic data, adequacy of capillary glycaemic monitoring, treatment administered during admission, and recommended therapy at discharge. RESULTS: The median age of the patients was 80 years [74-87], of which 561 (47%) were women, with a Charlson index of 4 points [2-6], and 742 (65%) were fragile. Median blood glucose on admission was 155 mg/dl [119-213]. On the third day, the number of capillary blood glucose levels in target (80-180 mg/dl) at pre-breakfast was 792/1126 (70.3%), pre-lunch 601/1083 (55.4%), pre-dinner 591/1073 (55.0%), and at night 317/529 (59.9%). A total of 35 patients (0.9%) were suffering from hypoglycemia. Treatment during hospitalization was performed with sliding scale insulin in 352 (40.5%) patients, with basal insulin and rapid insulin analogues in 434 (50%), or with diet exclusively in 101 (9.1%). A total of 735 (61.6%) patients had a recent HbA1c value. At discharge, the use of SGLT2i increased significantly (30.1% vs. 21.6%; p < 0.001), as did the use of basal insulin (25.3% vs. 10.1%; p < 0.001). CONCLUSIONS: There is an excessive use of sliding scale insulin as well as insufficient information on HbA1c values and prescription upon discharge of treatments with cardiovascular benefit.

Seguimiento a largo plazo de los pacientes operados de cáncer de pulmón / Spanish Society of Thoracic Surgery (SECT) consensus document. Long-term follow-up for operated patients with lung cancer

El tratamiento más efectivo para el cáncer de pulmón es la resección pulmonar completa, si bien las recidivas llegan hasta el 10% y la aparición de segundos primarios, hasta el 6%. Será, por tanto, indispensable el seguimiento de estos pacientes para la detección y tratamiento precoces de estos eventos; sin embargo, no existe una definición de la forma, tiempo y cadencia de estos seguimientos. En el presente documento de consenso, tratamos de definirlos con base en la evidencia científica disponible. Se realiza una revisión crítica de la bibliografía (metaanálisis, revisiones sistemáticas, revisiones, recomendaciones de consenso de sociedades científicas, estudios controlados aleatorizados, estudios controlados no aleatorizados, estudios observacionales y estudios de series de casos) y comunicaciones a los principales congresos de oncología y cirugía torácica en castellano, inglés y francés. Se clasifican las evidencias halladas siguiendo el sistema GRADE. Queda definido, según la evidencia existente, que se debe realizar un seguimiento del paciente resecado por cáncer pulmonar, así como que este seguimiento debe ser estrecho durante los primeros años y con realización de TC (no siendo necesario el seguimiento con tomografía por emisión de positrones-tomografía computarizada [PET-TC], biomarcadores o broncoscopia). Se recomienda también en ese seguimiento el cese del hábito tabáquico (AU)

The most effective treatment for lung cancer is complete lung resection, although recurrences reach up to 10% and the appearance of second neoplasms, up to 6%. Therefore, the follow-up of these patients will be essential for the early detection and treatment of these events; however, there is no definition of the form, time and cadence of these follow-ups. In this consensus document, we try to define them based on the available scientific evidence. A critical review of the literature is carried out (meta-analysis, systematic reviews, reviews, consensus recommendations of scientific societies, randomized controlled studies, non-randomized controlled studies, observational studies and case series studies) and communications to the main congresses on oncology and thoracic surgery in Spanish, English and French. The evidences found are classified following the GRADE system. It is defined according to the existing evidence that the patient resected for lung cancer should be followed up, as well as that this follow-up should be close during the first years and with CT (not being necessary to follow up with PET-CT, biomarkers or bronchoscopy). Cessation of smoking is also recommended in this follow-up (AU)

Utilidad de la ECMO sobre el injerto pulmonar disfuncionante en un modelo porcino estandarizado de trasplante unipulmonar / [Usefulness of ECMO on dysfunctional lung graft in a standardized porcine model of one-lung transplant]

Objetivo: Establecer un modelo de muerte encefálica y trasplante pulmonar y analizar el posible papel protector del oxigenador de membrana extracorpóreo (ECMO).Métodos: Se emplearon 20 cerdos hembras, 10 donantes y 10 receptoras. Las receptoras del Grupo A (n = 5) fueron sometidas a un trasplante unipulmonar izquierdo (Tx-UPI) sin ECMO. Las receptoras del Grupo B (n = 5) se sometieron a un Tx-UPI con ECMO venoarterial (ECMO-VA). Se recopilaron datos funcionales e histológicos en situación basal, a los 10 minutos de clampar el hilio derecho (Tiempo 1) y a las 2 horas (Tiempo 2). Se analizó la expresión proteica de marcadores de inflamación y de la ruta de hipoxia.Resultados: El modelo de muerte encefálica empleado, seguido de un tiempo de isquemia frío prolongado (20 horas) dio lugar a la aparición de un edema pulmonar severo. Tras el implante, 3 receptores del grupo A sobrevivieron hasta el Tiempo 2, falleciendo 2 por edema pulmonar masivo. Por el contrario, todos los animales del Grupo B sobrevivieron, siendo la PaO2 en ese momento de 462,72 mmHg. Hubo un incremento de la expresión de IL6, TNF, PCR, AC IX y el VEGF, así como un descenso en la expresión de IL8 y GLUT1, al usar la ECMO.Conclusiones: Se ha desarrollado un modelo porcino estandarizado y reproducible de muerte encefálica, que simula el proceso clínico de la donación pulmonar. Este modelo puede servir de plataforma para investigar posibles dianas terapéuticas. (AU)

Objective: Establish a model of brain death and lung transplantation and analyze the possible protective role of extracorporeal membrane oxygenation (ECMO).Methods: 20 female pigs were used, 10 donors and 10 recipients. Group A recipients (n = 5) underwent left-sided single- lung transplantation (LUCT-Tx) without ECMO. Group B recipients (n = 5) underwent ICU-Tx with venoarterial ECMO (VA-ECMO). Functional and histological data were collected at baseline, 10 minutes after clamping the right hilum (Time 1) and 2 hours (Time 2). Protein expression of inflammation markers and the hypoxia pathway was analyzed.Results: The brain death model used, followed by a prolonged cold ischemia time (20 hours) gave rise to the appearance of severe pulmonary edema. After implantation, 3 group A recipients survived until Time 2, with 2 dying from massive pulmonary edema. In contrast, all the animals in Group B survived, with PaO2 at that time being 462.72 mmHg. There was an increase in the expression of IL6, TNFα, CRP, AC IX and VEGF, as well as a decrease in the expression of IL8 and GLUT1, when using ECMO.Conclusions: A standardized and reproducible porcine model of brain death has been developed, which simulates the clinical process of lung donation. This model can serve as a platform to investigate possible therapeutic targets. (AU)

Raspberry Pi based photovoltaic I-V curve tracer.

This paper details the design and implementation of a photovoltaic current - voltage (I-V) tracer. The I-V tracer employs a capacitive load controlled by a raspberry pi model 4B. The complete measurement system includes protections, capacitor charging/discharging power electronics and current, voltage, irradiance and temperature sensors. Results, which include maximum power point, open circuit voltage, short circuit current and module efficiency, are displayed on an LCD touch display. Detailed description of the required software and the graphical user interface is also presented. This measurement system is very useful for testing photovoltaic installations, allowing an immediate verification whether the panels fulfill with the specifications and detection of possible failures.

Streptococcus pneumoniae prevalence in nasopharynx, oropharynx and gingival sulcus in Brazilian adults:A preliminary study.

AIM: This study aimed to evaluate the prevalence of S. pneumoniae colonization in three different sites in healthy adults: nasopharynx, oropharynx and gingival sulcus. METHODS: Two-hundred and sixty five adults, aged 20-60 years, who attended dental clinics in one public university (n = 106) and one military institution (n = 159) were enrolled in this study. Pneumococcal detection was performed by direct culture (DC) and PCR for lytA gene after a broth enrichment step. Capsular types were determined by sequential multiplex PCR. RESULTS: We identified 18 (6.8%) pneumococcal carriers among 265 adults by PCR, but only one (0.4%) pneumococcal strain was isolated by DC method. Oropharynx (17; 6.4%) was the main source of S. pneumoniae. Colonization of gingival sulcus and nasopharynx was found in 4 (1.5%) and 2 (0.8%) adults, respectively. Nine distinct capsular types were detected from 9 adults and co-colonization with 2 serotypes was confirmed in 4 (1.5%) subjects. Factors associated with carriage were being females, low level of schooling, non-military and regular medication. We observed a low (6.8%) pneumococcal carriage prevalence, but oropharyngeal samples yielded more sensitive results, especially by the PCR-based detection methodology. CONCLUSION: Gingival sulcus was found to be a possible reservoir for S. pneumoniae independently of the oropharynx or nasopharynx colonization.

Effect of supplementation of valine to chicken extender on sperm cryoresistance and post-thaw fertilization capacity.

Recent reports showed a positive correlation between frozen-thawed rooster sperm DNA integrity and the concentrations of valine in seminal plasma. The present study evaluated the effect of supplementing valine to semen extender for freezing sperm of 2 endangered local Spanish chicken breeds with different sperm cryoresistance: Red Villafranquina (VF) showing low sperm DNA integrity after cryopreservation and Quail Castellana that shows higher DNA integrity. One pool of semen per breed was obtained twice a week for 10 wk (n = 40, 20 per breed). Each pool was divided into 2 fractions. One of these fractions was frozen in presence of valine as additive in the extender (concentration 10 mmol), whereas the other was used as control. The evaluation of the samples before and after freezing-thawing included motility (CASA-Mot system), viability (propidium iodide and SYBR-14), DNA integrity (terminal deoxynucleotidyl transferase dUTP nick end labeling), and fertility rate (percentage of eggs with blastoderm development after artificial insemination). Supplementation of valine increased several motility variables of fresh semen. In VF breed, valine increased percentage of progressive motile sperm (P = 0.025), curvilinear velocity (P = 0.033), straight-line velocity (P = 0.040), and average path velocity (P = 0.033), whereas progressive motile sperm (P = 0.019), curvilinear velocity (P = 0.006), straight-line velocity (P = 0.003) and average path velocity (P = 0.004) were improved in the Quail Castellana breed. Valine addition increased the DNA integrity of cryopreserved semen (decreased post-thaw DNA fragmentation) in both breeds, with a significant effect (P = 0.002) in VF (36.3% VF-control vs 31%VF-valine). As expected, Quail Castellana cryopreserved sperm control showed higher fertility rate (34.4% ± 12.1) than VF cryopreserved sperm control (16.1% + 6.2). Supplementing valine to the freezing extender doubled (P = 0.026) the fertility rate of VF (32.6% ± 12.2) compared with the control (16.1% + 6.2). In conclusion, supplementation of valine to chicken freezing extenders shows a positive effect on DNA fragmentation and fertilizing ability of frozen-thawed sperm, with a better response in a breed considered as the lowest freezer in our conservatory.

Evaluation of genetic risk related to catechol-O-methyltransferase (COMT) and ß2-adrenergic receptor (ADRB2) activity in different diagnostic subgroups of temporomandibular disorder in Brazilian patients.

The aim of this study was to evaluate the possible association between polymorphisms in the catechol-O-methyltransferase (COMT) and ß2-adrenergic receptor (ADRB2) genes and muscular temporomandibular disorders (TMD). This was a case-control study. Individuals were evaluated using the Research Diagnostic Criteria for Temporomandibular Disorders and were divided into three groups: unaffected (no TMD) (n=154); exclusively muscular TMD (n=49); exclusively articular TMD (n=49). Genomic DNA was obtained from saliva samples, and single nucleotide polymorphisms in the COMT (rs165774, rs6269, rs9332377) and ADRB2 (rs2053044, rs1042713, rs1042714) genes were investigated. The TT genotype for the COMT rs9332377 gene was highly associated with the presence of muscular TMD (P= 0.03). With respect to the ADRB2 gene, the non-polymorphic AA genotype in the rs1042713 region was more prevalent in the articular TMD group than in the muscular TMD group (P= 0.05). This study supports the hypothesis that alterations in the COMT and ADRB2 genes influence the muscular pathophysiology.

Marcadores pronóstico en la carcinogénesis pulmonar. Ruta SIAH2-DYRK2 / Prognostic markers in lung carcinogenesis. SIAH2-DYRK2 route

El cáncer de pulmón (CP) es la primera causa de muerte por cáncer en el mundo. Su elevada mortalidad refleja, en parte, la limitada eficacia de las terapias actualmente disponibles. Dada la pobre supervivencia actual del CP, y la demostrada evidencia de que el diagnóstico precoz reduce la mortalidad, ha cobrado especial interés la búsqueda de biomarcadores. Recientemente, se ha atribuido a DYRK2 un papel relevante en el desarrollo y progresión tumoral relacionado con la inducción de la apoptosis en respuesta al estrés oncogénico. Así, se identificó a DYRK2 como el gen más frecuentemente sobre- expresado en el adenocarcinoma de pulmón, siendo además un factor pronóstico favorable en estos tumores. Asimismo, se ha demostrado la existencia de una regulación mutua entre DYRK2 y la ubiquitín-ligasa SIAH2, en el control de la respuesta a hipoxia y el daño genotóxico. La búsqueda de nuevas dianas y estrategias terapéuticas supone un paso clave para la lucha contra el cáncer de pulmón. El objetivo del trabajo fue investigar qué papel juegan las proteínas SIAH2-DYRK2 en la carcinogénesis pulmonar, así como determinar el impacto clínico-patológico de su expresión en el tejido neoplásico. La modulación de la ruta SIAH2-DYRK2 podría ser empleada como una terapia dirigida en pacientes con cáncer de pulmón

Lung cancer (LC) continues to be the leading cause of cancer-related mortality worldwide. The high mortality highlights the limited efficacy of available therapies for LC treatment. Given the poor survival rate of LC, and considering that early diagnosis reduces mortality, special interest exists nowadays in searching for lung cancer biomarkers. Recently, it has been suggested a possible role of DYRK2 in the development and progression of tumors, related to the induction of apoptosis in response oncogenic stress. In this regard, DYRK2 was identified as the most commonly up-regulated gene in lung adenocarcinomas, as well as a favourable prognostic factor in these tumors. Moreover, a mutual regulation between DYRK2 and the ubiquitin-ligase SIAH2 in response to hypoxia and DNA-damage signaling pathways has been demonstrated. It is of paramount importance to search for new targets and therapeutic strategies in lung cancer. The aim of the study was to analyse the role of SIAH2-DYRK2 in the development of lung cancer, and to assess the clinical and pathological effects of the expression of these proteins in lung cancer tissue. Modulation of the route SIAH2- DYRK2 might be used as a new targeted therapy in lung cancer patients

Meat quality traits in the Greater rhea (Rhea americana) as influenced by muscle, sex and age.

Meat from the Greater rhea (Rhea americana) could compete with traditional red meats, diversifying the market of protein products of animal origin. The meat from 32 rheas was used to study quality aspects and this included ultimate pH (pHu), color, water-holding capacity (WHC%), cooking loss (CL%) and tenderness. The muscles sampled were the Gastrocnemius pars externa, Iliofibularis and Obturatorius medialis from both sexes at multiple ages (10, 12, 14, 16 months). Age at slaughter affected WHC%, CL%, and color in raw meat and tenderness in cooked meat. Muscles under study showed differences in terms of pHu, raw meat color, and tenderness of cooked meat. Sex did not have a significant effect on any of the variables studied. According to our results, rhea meat from younger animals, between 10 to 14 months old, was tender and moderately juicy and the visual color was appreciated by the consumers.

"Evita Una Muerte, Esta en Tus Manos" Program: Bystander First Aid Training for Terrorist Attacks.

BACKGROUND: The latest terrorist attacks in Europe and in the rest of the world, and the military experience in the most recent conflicts leave us with several lessons learned. The most important is that the fate of the wounded rests in the hands of the one who applies the first dressing, because the victims usually die within the first 10 minutes, before professional care providers or police personnel arrive at the scene. A second lesson is that the primary cause of preventable death in these types of incidents involving explosives and firearms is massive hemorraghe. OBJECTIVE: There is a need to develop a training oriented to citizens so they can identify and use available resources to avoid preventable deaths that occur in this kind of incidents, especially massive hemorrhage. METHODS: A 7-hour training intervention program was developed and conducted between January and May 2017. Data were collected from participants' answers on a multiple-choice test before and after undertaking the training. Improved mean score for at least 75% of a group's members on the posttraining test was considered reflective of adequate knowledge. RESULTS: A total of 173 participants (n = 74 men [42.8%]; n = 99 women [57.2%]) attended the training. They were classified into three groups: a group of citizens/ first responders with no prior health training, a group of health professionals, and a group of nursing students. Significant differences (ρ < .05) between mean pre- and post-training test scores occurred in each of the three groups. CONCLUSION: There was a clear improvement in the knowledge of the students after the training when pre- and post-training test scores were compared within the three groups. The greatest improvement was seen in the citizens/first responders group.

Efectos del sistema endocannabinoide en el sistema respiratorio. Papel de los receptores TRPV1 en la fibrogénesis pulmonar / Endocannabinoid system effects on the respiratory system. The role of TRPV1 receptors in pulmonary fibrosis

Objetivos: establecer un modelo murino de fibrosis pulmonar inducida por bleomicina, investigando el posible papel protector del sistema endocannabinoide (SE) frente a la fibrosis. Métodos: se emplearon ratones salvajes (C5BL/6 y Balb/c) así como la cepa TRPV1-/-. Tras una única dosis intratraqueal de bleomicina, se analizó la respuesta fibrótica mediante un análisis histológico, la determinación de la expresión de marcadores del proceso profibrótico, el estudio de la actividad mieloperoxidasa y del contenido en hidroxiprolina del pulmón, así como el análisis de la expresión génica de VIP, PACAP, IL-1β, IL-6, TNF-α e IL-11, y el estado de activación de las rutas MAPKs (fosfo-JNK, fosfo-ERK) de la ruta de NF-κB (p-IκBα), la ruta de β-catenina y del TGFβ (GSK-3B), la activación de SMAD (pSMAD2) y pSTAT3, a nivel proteico. Resultados: la fibrosis pulmonar inducida por bleomicina en los ratones de la cepa TRPV- /- fue más severa que en la cepa salvaje C5BL/6. El contenido en hidroxiprolina y la actividad mieloperoxidasa fue mayor en los ratones TRPV1-/-. Se detectó un incremento significativo en la expresión génica de citoquinas proinflamatorias (TNF-a, IL-1b, IL11 e IL-6), pero no de VIP o PACAP, en la cepa TRPV1-/-. A nivel proteico, la expresión de pIKBα, pSTAT3, pSMAD2 y pJNK, pero no la de pERK, se vio incrementada en los ratones TRPV1-/-. Conclusiones: el modelo murino de fibrosis pulmonar inducida por bleomicina sigue siendo clave para continuar profundizando los conocimientos acerca de la patogénesis de la FPI. La modulación del SE podría tener un papel protector frente a la fibrosis pulmonar

Objectives: to establish a murine model of bleomycin-induced pulmonary fibrosis, analysing the possible protective role of the Endocannabinoid System (ES) against fibrosis. Methods: wild C5BL/6 and Balb/c mice, as well as the genetically modified strain TRPV1- /- were used. After a single dose of intratracheal bleomycin, the fibrotic response was analysed though histologic studies, the assessment of proinflammatory markers, myeloperoxidase activity, hydroxyproline content, genetic expression of VIP, PACAP, IL-1 β, IL-6, TNF-α and IL-11, as well as MAPK route (phospho-JNK, phospho-ERK), NF-κB (p-IκBα), β-cathenin, TGF-β (GSK-3B), SMAD (p-SMAD2) and pSTAT3, at a protein level. Results: pulmonary fibrosis was more severe in TRPV1-/- mice compared to C5BL/6 mice. A significant increase in proinflammatory markers such as TNF-α, IL-1β, IL11 and IL-6, but not VIP or PACAP, was observed. pIKBα, pSTAT3, pSMAD2 and pJNK, but not pERK, were increased at a protein level in TRPV-/- mice. Conclusions: the murine model of bleomycin-induced lung fibrosis remains a keystone to pioneer current investigation in lung fibrosis. Modulation of the ES might have a protective role

Haplotypes of the RANK and OPG genes are associated with chronic arthralgia in individuals with and without temporomandibular disorders.

The aim of this study was to evaluate the association between genetic polymorphisms and the comorbid presence of chronic systemic arthralgia in patients with articular temporomandibular disorders (TMD). Subjects were evaluated for the presence of TMD and asked about the presence of chronic joint pain. Four groups were included in the study: articular TMD and systemic arthralgia (n=85), no articular TMD and systemic arthralgia (n=82), articular TMD and no systemic arthralgia (n=21), no articular TMD and no systemic arthralgia (control, n=72). A total of 14 single nucleotide polymorphisms in the OPG, RANK, and RANKL genes were investigated. In the statistical analysis, a P-value of <0.05 was considered significant. For the OPG gene, an association was observed between the group with chronic arthralgia and joint TMD and the control group (P=0.04). There was also a tendency towards an association of the haplotype CGCCAA with an increased risk of developing chronic joint pain, even in the absence of TMD (P=0.06). For the RANK gene, the AGTGC haplotype was associated with the lowest risk of presenting chronic joint pain in individuals without TMD (P=0.03). This study supports the hypothesis that changes in the OPG and RANK genes influence the presence of chronic joint pain in individuals with and without TMD.

Can by-products replace conventional ingredients in concentrate of dairy goat diet?

Intensive dairy goat production in the Mediterranean basin is based on imported conventional ingredients to be included in concentrates. Fourteen Murciano-Granadina goats in the middle of the third lactation were allocated into 2 groups of 7 animals each fed, respectively, a control diet based on alfalfa hay and concentrate in a 40:60 ratio, and a diet in which the concentrate included tomato fruits, citrus pulp, brewer's grain and brewer's yeast (T100CBY) to study the effect of diet on nutrient utilization, ruminal fermentation, purine derivatives excretion in urine, milk yield and composition, and methane emissions. No effect of the diet on total dry matter intake was observed. Digestibility of neutral detergent fiber and acid detergent fiber were higher for T100CBY compared with the control diet. The N in feces and urine was lower and balance and retained N were higher in animals fed T100CBY than the control diet. Milk protein N and energy were similar for both diets. Metabolizable energy per energy intake and metabolizable energy per digestible energy were higher and energy in methane was lower with diet T100CBY than with the control. Milk yield and composition were not affected by diet, with the exception of protein, casein, and total solids, which were higher for diet T100CBY than the control. Diet T100CBY promoted less saturated fatty acids and higher mono- and polyunsaturated fatty acids in milk than the control diet. Diet T100CBY produced less methane and NH3 concentration in the rumen, higher propionate, and a lower acetate-to-propionate ratio without an effect on the volatile fatty acid concentration. The concentrate with by-products did not affect urinary excretion of total purine derivatives, reduced feeding costs, and increased profit margin by 14 and 16% compared with the control. The mixture of tomato fruits, citrus pulp, brewer's grain, and brewer's yeast could replace 47% of conventional ingredients (corn, wheat bran, sunflower meal, and soy flour) in the concentrate of the dairy goat diet, reducing feeding cost and methane production, leading to a healthier fatty acids profile in milk without compromising nutrient utilization or milk yield.

Association between temporomandibular disorders and pain in other regions of the body.

The pain from temporomandibular disorder (TMD) is often associated with physical symptoms of other chronic pain disorders and comorbidities, such as generalised muscle and joint pain. However, this association is not widely studied. To evaluate the prevalence of comorbid pain in joints, specifically in the knees, hips, ankles, shoulders, wrists and elbows, in individuals with and without TMD. We evaluated 337 patients from a public hospital in the city of Rio de Janeiro, Brazil. The Research Diagnostic Criteria for TMD questionnaire were used for the diagnosis of TMD. To assess the presence of other joint pain, the patients were asked to answer questions considering: the presence of pain in the knee, hip, ankle, shoulder, wrist and elbow joints and time duration of pain. Individuals with TMD are 5·5 times more likely to present with other joint pain compared with those without the disorder. TMD muscle disorders were most associated with a higher number of pain at the other locations. There was a significant association between the presence of pain at the other locations, muscle (P < 0·001) and joint disorders (P = <0·001), as well as age advance, in TMD participants, showed to be a covariate factor for pain at the other locations. Individuals with TMD showed a high prevalence of pain in other joints of the body when compared with individuals without the disorder, and knee pain was the most prevalent pain complaint.

Oxidative stress downstream of mTORC1 but not AKT causes a proliferative defect in cancer cells resistant to PI3K inhibition.

Compounds targeting phosphatidylinositol-3-kinase/mammalian target of rapamycin (PI3K/mTOR) signaling are being investigated in multiple clinical settings, but drug resistance may reduce their benefit. Compound rechallenge after drug holidays can overcome such resistance, yet little is known about the impact of drug holidays on cell biochemistry. We found that PI3K inhibitor (PI3Ki)-resistant cells cultured in the absence of PI3Ki developed a proliferative defect, increased oxygen consumption and accumulated reactive oxygen species (ROS), leading to lactate production through hypoxia-inducible factor-1α. This metabolic imbalance was reversed by mammalian target of rapamycin complex 1 (mTORC1) inhibitors. Interestingly, neither AKT nor c-MYC was involved in mediating the metabolic phenotype, despite the latter contributing to resistant cells' proliferation. These data suggest that an AKT-independent PI3K/mTORC1 axis operates in these cells. The excessive ROS hampered cell division, and the metabolic phenotype made resistant cells more sensitive to hydrogen peroxide and nutrient starvation. Thus, the proliferative defect of PI3Ki-resistant cells during drug holidays is caused by defective metabolic adaptation to chronic PI3K/mTOR pathway inhibition. This metabolic imbalance may open the therapeutic window for challenge with metabolic drugs during drug holidays.

Resultados de la resección pulmonar infralobar, comparada con la lobectomía, en el tratamiento quirúrgico del carcinoma broncogénico en estadio precoz / Outcomes of sublobar resection, compared with lobectomy, in the surgical management of early stage non-small cell lung cancer

OBJETIVOS: la resección infralobar (RI) en el carcinoma broncogénico de célula no pequeña (CBCNP) en estadio precoz está ganando popularidad. Sin embargo, la cantidad óptima de parénquima pulmonar a resecar sigue siendo objeto de controversia. Analizamos si la RI difiere de la lobectomía (L) como tratamiento quirúrgico estándar de los pacientes con CBCNP en estadio precoz. MÉTODOS: se analizaron 493 resecciones pulmonares consecutivas realizadas en un periodo de 14 años. 266 pacientes con CBCNP en estadio I fueron sometidos a una lobectomía (L = 178), o a una resección pulmonar atípica/segmentectomía (RI = 88). Se compararon factores demográficos, oncológicos, quirúrgicos y postoperatorios. RESULTADOS: no se observaron diferencias en las características de los pacientes, la mortalidad perioperatoria o la tasa de complicaciones. En los pacientes con CBCNP en estadio I (n = 266) la tasa de recurrencia loco-regional (RI vs L): 14% vs 16% (p = 0,06), metástasis a distancia: 8% vs 9% (p = 0,33), supervivencia (a los 3, 5 años): 78%, 74% vs 74%, 69% (p = 0,37), supervivencia libre de enfermedad (a los 3, 5 años): 82%, 36% vs 80%, 56% (p = 0,93), supervivencia libre de metástasis a distancia (a los 3, 5 años): 90%, 80% vs 86%, 83% (p = 0,73). Complicaciones postquirúrgicas: 30% vs 36% (p = 0,21), mortalidad perioperatoria: 2% vs 5% (p = 0,64). CONCLUSIONES: la resección pulmonar infralobar posee unas tasas aceptables de morbimortalidad y puede ser equivalente a la lobectomía, desde el punto de vista oncológico, en el CBCNP en estadio I

OBJECTIVE: sublobar resection (SLR) for early stage NSCLC is gaining acceptance in the recent years, especially in aging population or with decreased pulmonary function. The optimal extent of surgical resection in stage I NSCLC remains controversial. This study was designed to determine whether SLR differs from lobectomy (L) as the standard of care for the surgical treatment of patients with early stage NSCLC. METHODS: we retrospectively reviewed 493 consecutive lung resections performed over a 5-year period at a single center. A total of 266 patients with NSCLC underwent either lobectomy (L Group: 178 patients), or wedge/segmentectomy (SLR Group: 88 patients) for stage I NSCLC. Demographic, oncological, surgical and postoperative variables were compared between groups. RESULTS: overall, no differences were observed between SLR and L in patient characteristics, 30-day mortality and complications. In stage I patients (n = 266), local recurrence (SLR vs L): 14% vs 16% (p = .06), distant recurrence: 8% vs 9% (p = .33), survival (at 3, 5 years): 78%, 74% vs 74%, 69% (p = .37), local disease-free survival (at 3, 5 years): 82%, 36% vs 80%, 56% (p = .93), distant disease-free survival (at 3, 5 years): 90%, 80% vs 86%, 83% (p = .73). Postoperative complications: 30% vs 36% (p = .21), 30-day mortality: 2% vs 5% (p = .64). CONCLUSION: sublobar resection has acceptable morbidity and mortality rates, and could be oncologically equivalent to lobectomy in stage I NSCLC

ESRRB polymorphisms are associated with comorbidity of temporomandibular disorders and rotator cuff disease.

Temporomandibular disorders (TMD) are associated with comorbidity. Shoulder pain is among the symptoms associated with TMD. The purpose of this study was to investigate the association between TMD and rotator cuff disease (RCD) and related genetic aspects. All subjects underwent orofacial and shoulder examinations. The control group comprised 30 subjects with no pain. Affected subjects were divided into three groups: RCD (TMD-free, n=16), TMD (RCD-free, n=13), and TMD/RCD (patients with both RCD and TMD, n=49). A total of eight single nucleotide polymorphisms in the ESRRB gene were investigated. A chemiluminescent immunoassay was used to measure estradiol levels. Surface electromyography recorded head and cervical muscle activity. The χ(2) test and Student t-test/Mann-Whitney test were used to assess the significance of nominal and continuous variables. A P-value of <0.05 was considered significant. TMD subjects were seven times more susceptible to RCD than controls. The rs1676303 TT (P=0.02) and rs6574293 GG (P=0.04) genotypes were associated with RCD and TMD, respectively. TMD/RCD subjects showed associations with rs4903399 (P=0.02), rs10132091 (P=0.02), and CTTCTTAG/CCTCTCAG (P=0.01) haplotypes and lower muscle activity. Estradiol levels were similar among groups. This study supports TMD as a risk factor for RCD. ESRRB haplotypes and low muscle activity are common biomechanical characteristics in subjects with both diseases.

Aplicación de un sistema in silico múltiple para la priorización en la selección de compuestos antimaláricos / Multiple in silico genetic toxicity alerting tools for antimalarial compounds prioritization

Introducción: Como parte del compromiso de GSK en la reducción del fracaso en las fases de desarrollo clínico y preclínico, se ha implementado en las fases más tempranas de desarrollo una estrategia para evitar los problemas de genotoxicidad que son los que, en mayor manera, pueden obstaculizar la progresión a fases más avanzadas. El objetivo de este trabajo es aplicar la nueva estrategia de GSK para la priorización de compuestos que permita seleccionar aquellas estructuras con menor riesgo de genotoxicidad utilizando una combinación de herramientas computacionales que predice el resultado del test de Ames. Materiales y Métodos: Compuestos de la colección de GSK, activos en el screening fenotípico frente a P. falciparum, fueron utilizados en este estudio. Tres modelos, Derek Nexus (Lhasa Limited, Leeds, UK), Leadscope y un método de mecánica cuántica desarrollado internamente se utilizaron para las predicciones in silico. Resultados: la combinación de los tres modelos de predicción tuvo un porcentaje de éxito del 75% con sólo 1 falso positivo. Conclusiones: Moléculas con 2 o más alertas de genotoxicidad generadas por este sistema múltiple deberían ser despriorizadas o ensayadas experimentalmente cuanto antes para descartar su riesgo de genotoxicidad (AU)

Introduction: As part of the commitment of GSK in reducing attrition rate in clinical and preclinical stages, it has been set up in early stages of development (H2L, Lead Op) a candidate quality strategy to avoid genotoxicity liabilities that mainly can stop the progression of compound towards advanced stages. The aim of the study is to apply the new strategy in order to triage structures with less genotoxicity risk by means an in silico multiple system that predicts the outcome of Ames test. Material & Methods: Active compounds against P. falciparum phenotypic screening from GSK collection were used. Three different models: Derek Nexus (Lhasa Limited, Leeds, UK), Leadscope and a quantum mechanics method developed internally were used for in silico predictions. Results: The use of three models have an accurately success rate, greater than 75% with only 1 false positives. Conclusions: Those molecules that fire 2 or more genotoxicity alerts should be deprioritised or tested experimentally in Ames test to confirm or discharge the genotoxicity risk (AU)

Quimerismo donante-receptor como origen del desarrollo de bronquiolitis obliterante en un modelo experimental de retrasplante de tráquea en ratas / Donor-receiver chimerism as the ori gin of obliterative bronchiolitis in an experimental model for trachea re transplant in rats

OBJETIVOS: 1. Desarrollar un modelo de bronquiolitis obli-terante en ratas (BO), mediante trasplante heterotópico de tráquea; 2. Eliminar el componente de rechazo alogénico me-diante el reimplante del injerto en un animal isogénico; y 3. Estudiar la respuesta inflamatoria persistente que podría auto-perpetuar la lesión.MÉTODOS: Se utilizaron ratas de las razas Lewis (LW), Wistar (W) y Brown Norway (BN). Se realizaron trasplantes singéni-cos (LW-LW, n=14; W-W, n=6; y BN-BN, n=6) y alogénicos AB (LW-W, n=6; BN-LW, n=6; y W-LW, n=6), alojando el injerto en el tejido celular subcutáneo cervical. Tras 15 días, se explantó el injerto e implantó en una tercera rata singéni-ca o alogénica por otros 15 días, estableciendo un modelo de retrasplante A-B-A y A-B-B. Los injertos se procesaron para realizar estudios histológicos e inmunohistoquímicos. El ori-gen de las células epiteliales se analizó mediante PCR.RESULTADOS: El retrasplante de tráquea, tanto en el diseño A-B-B como A-B-A, dió lugar a la aparición de una rápida respuesta inflamatoria compatible con un proceso de BO, en aquellos animales que habían desarrollado rechazo por tras-plante alogénico previo. En trasplantes ♀-♂-♀, se detectaron células con el cromosoma Y en tráqueas del 2º receptor ♀.CONCLUSIONES: En el modelo de retrasplante de tráquea en ratas, junto a los hallazgos típicos de BO se produce una res-puesta inflamatoria leve-moderada compatible con un recha-zo celular MHC incompatible. Células procedentes del primer receptor se integrarían en la tráquea del segundo trasplante, produciéndose un quimerismo donante receptor, que sería el responsable, en último término, del desarrollo de BO

OBJECTIVES: 1. Develop an obliterative bronchiolitis (OB) model in rats, by means of heterotopic trachea transplant; 2. Eliminate the allogenic rejection component by re-implanting a graft in an isogenic animal; and 3. Study the persistent in-flammatory response that could self-perpetuate the injury. METHODS: The following rat breeds were used: Lewis (LW), Wistar (W) and Brown Norway (BN). Syngenic (LW-LW, n=14; W-W, n=6; and BN-BN, n=6) and allogenic AB (LW-W, n=6; BN-LW, n=6; and W-LW, n=6) transplants were performed, housing the graft in the cervical subcutaneous ce-llular tissue. After 15 days, the graft was removed and implan-ted into a third syngenic or allogenic rat for another 15 days, to establish a re-transplant model A-B-A and A-B-B. The grafts were processed to carry out histological and immunohistoche-mical studies. The origin of the epithelial cells was analyzed using PCR. RESULTS: The tracheal re-transplant, both in the A-B-B and A-B-A design, gave rise to the appearance of a rapid inflam-matory response compatible with OB process, in those ani-mals that rejected the transplant due to previous allogenic transplant. In ♀ -♂ -♀ transplants, cells were detected with the Y chromosome in trachea of the 2nd ♀ receiver. CONCLUSIONS: In the trachea re-transplant model in rats, together with typical OB discoveries, a compatible slight-moderate inflammatory response takes place with an MHC incompatible cellular rejection. Cells from the first receiver became integrated into the trachea of the second transplant, producing a donor-receiver chimerism that would, in the final location, be responsible for the development of OB. Key words: Lung transplant, chronic rejection, obliterative bronchiolitis, chronic dysfunction of the lung graft