Biomarcadores asociados con la supervivencia y la respuesta terapéutica a la radioembolización con esferas cargadas de itrio-90 en las metástasis hepáticas del carcinoma colorrectal: nuestra experiencia / Biomarkers associated with survival and favourable outcome of radioembolization with yttrium-90 glass microspheres for colon cancer liver metastases: Single centre experience

Objetivo: Analizar la eficacia terapéutica, seguridad y valor pronóstico de diferentes biomarcadores de la radioembolización transarterial con esferas de itrio-90 (TARE) en pacientes con metástasis hepáticas de cáncer colorrectal. Material y métodos: Estudio prospectivo que incluye los pacientes con metástasis hepáticas de cancer colorrectal tratados con TARE entre noviembre de 2015 y junio de 2020. Se analizó la respuesta terapéutica (3 y 6 meses, criterios RECIST v1.1) mediante el cálculo de las tasas de respuesta tumoral objetiva (ORR) y de control de la enfermedad (DCR), así como la asociación de los biomarcadores con la respuesta terapéutica y la supervivencia global (SG) y libre de progresión (SLP). Resultados: Treinta TARE en 23 pacientes (edad media 61,61±9,13 años; 56,5% varones). La ORR a los 3 meses fue del 16,7% y el DCR del 53,3%. A los 6 meses progresaron el 80% de los pacientes. La ORR y DCR se asociaron con la edad (p=0,047), tratamiento con bevacizumab (p=0,008), hemoglobina (p=0,008), NLR (p=0,040), albúmina (p=0,012) y GPT (p=0,023) previas a la TARE, y la dosis absorbida tumoral estimada>115Gy (p=0,033). La mediana de SG fue de 12 meses (IC 95%: 4,75-19,25 meses) y de SLP 3 meses (IC 95%: 2,41-3,59 meses). La SG se asoció con la cirugía del tumor primario (p=0,019), mutación KRAS (p=0,024), hemoglobina (p=0,009), NLR (p=0,005) y PLR (p=0,042) previos a la TARE. Conclusión: Los biomarcadores con capacidad para predecir el pronóstico y respuesta terapéutica a la TARE incluyen desde parámetros bioquímicos a factores relacionados con la dosimetría tumoral estimada (AU)

Objetivo: To determine the therapeutic effectiveness and safety of transarterial radioembolization (TARE) with Yttrium-90 in patients with colorectal cancer (CRC) liver metastases and to evaluate the prognostic value of different biomarkers. Material and methods: This prospective longitudinal study enrolled consecutive patients with CRC liver metastases treated with TARE between November 2015 and june 2020. The therapeutic response at three and six months (RECIST1.1 criteria) and the relationship of biomarkers with therapeutic response, by calculating objective tumor response rates (ORR) and disease control (DCR), and overall survival (OS) and progression-free (PFS). Results: Thirty TAREs were performed in 23 patients (mean age, 61,61±9,13 years; 56,5% male). At three months, the objective response rate (ORR) was 16,7% and the disease control rate (DCR) 53,3%. At six months, the disease progressed in 80%. The ORR and DCR were significantly associated with age at diagnosis (P=.047), previous bevacizumab treatment (P=.008), pre-TARE haemoglobin (P=.008), NLR (P=.040), pre-TARE albumin (P=.012), pre-TARE ALT (P=.023) and tumour-absorbed dose>115Gy (P=.033). Median overall survival (OS) was 12 months (95% CI, 4.75-19.25 months) and median progression-free survival (PFS) 3 months (95% CI, 2.41-3.59). OS was significantly associated with primary tumour resection (P=.019), KRAS mutation (HR: 5.15; P=.024), pre-TARE haemoglobin (HR: .50; p=.009), pre-TARE NLR (HR: 1.65; P=.005) and PLR (HR: 1.01; P=.042). Conclusion: TARE prognosis and therapeutic response were predicted by different biomarkers, ranging from biochemical parameters to tumour dosimetrics (AU)

Biomarkers associated with survival and favourable outcome of radioembolization with yttrium-90 glass microspheres for colon cancer liver metastases: Single centre experience.

OBJECTIVE: To determine the therapeutic effectiveness and safety of transarterial radioembolization (TARE) with Yttrium-90 in patients with colorectal cancer (CRC) liver metastases and to evaluate the prognostic value of different biomarkers. MATERIAL AND METHODS: This prospective longitudinal study enrolled consecutive patients with CRC liver metastases treated with TARE between November 2015 and june 2020. The therapeutic response at three and six months (RECIST1.1 criteria) and the relationship of biomarkers with therapeutic response, by calculating objective tumor response rates (ORR) and disease control (DCR), and overall survival (OS) and progression-free (PFS). RESULTS: Thirty TAREs were performed in 23 patients (mean age, 61.61 ±â€¯9.13 years; 56.5% male). At three months, the objective response rate (ORR) was 16.7% and the disease control rate (DCR) 53.3%. At six months, the disease progressed in 80%. The ORR and DCR were significantly associated with age at diagnosis (P = 0.047), previous bevacizumab treatment (P = 0.008), pre-TARE haemoglobin (P = 0.008), NLR (P = 0.040), pre-TARE albumin (P = 0.012), pre-TARE ALT (P = 0.023) and tumour-absorbed dose > 115 Gy (P = 0.033). Median overall survival (OS) was 12 months (95% CI, 4.75-19.25 months) and median progression-free survival (PFS) 3 months (95% CI, 2.41-3.59). OS was significantly associated with primary tumour resection (P = 0.019), KRAS mutation (HR: 5.15; P = 0.024), pre-TARE haemoglobin (HR: 0.50; p = 0.009), pre-TARE NLR (HR: 1.65; P = 0.005) and PLR (HR: 1.01; P = 0.042). CONCLUSION: TARE prognosis and therapeutic response were predicted by different biomarkers, ranging from biochemical parameters to tumour dosimetrics.

Biomarkers associated with survival and favourable outcome of radioembolization with yttrium-90 glass microspheres for colon cancer liver metastases: Single centre experience. / Biomarcadores asociados con la supervivencia y la respuesta terapéutica a la radioembolización con esferas cargadas de itrio-90 en las metástasis hepáticas del carcinoma colorrectal: nuestra experiencia.

OBJETIVE: To determine the therapeutic effectiveness and safety of transarterial radioembolization (TARE) with Yttrium-90 in patients with colorectal cancer (CRC) liver metastases and to evaluate the prognostic value of different biomarkers. MATERIAL AND METHODS: This prospective longitudinal study enrolled consecutive patients with CRC liver metastases treated with TARE between November 2015 and june 2020. The therapeutic response at three and six months (RECIST1.1 criteria) and the relationship of biomarkers with therapeutic response, by calculating objective tumor response rates (ORR) and disease control (DCR), and overall survival (OS) and progression-free (PFS). RESULTS: Thirty TAREs were performed in 23 patients (mean age, 61,61±9,13 years; 56,5% male). At three months, the objective response rate (ORR) was 16,7% and the disease control rate (DCR) 53,3%. At six months, the disease progressed in 80%. The ORR and DCR were significantly associated with age at diagnosis (P=.047), previous bevacizumab treatment (P=.008), pre-TARE haemoglobin (P=.008), NLR (P=.040), pre-TARE albumin (P=.012), pre-TARE ALT (P=.023) and tumour-absorbed dose>115Gy (P=.033). Median overall survival (OS) was 12 months (95% CI, 4.75-19.25 months) and median progression-free survival (PFS) 3 months (95% CI, 2.41-3.59). OS was significantly associated with primary tumour resection (P=.019), KRAS mutation (HR: 5.15; P=.024), pre-TARE haemoglobin (HR: .50; p=.009), pre-TARE NLR (HR: 1.65; P=.005) and PLR (HR: 1.01; P=.042). CONCLUSION: TARE prognosis and therapeutic response were predicted by different biomarkers, ranging from biochemical parameters to tumour dosimetrics.

Early socialization and environmental enrichment of lactating piglets affects the caecal microbiota and metabolomic response after weaning.

The aim of this study was to determine the possible impact of early socialization and an enriched neonatal environment to improve adaptation of piglets to weaning. We hypothesized that changes in the microbiota colonization process and in their metabolic response and intestinal functionality could help the animals face weaning stress. A total of 48 sows and their litters were allotted into a control (CTR) or an enriched treatment (ENR), in which piglets from two adjacent pens were combined and enriched with toys. The pattern of caecal microbial colonization, the jejunal gene expression, the serum metabolome and the intestinal physiology of the piglets were assessed before (-2 d) and after weaning (+ 3d). A differential ordination of caecal microbiota was observed after weaning. Serum metabolome suggested a reduced energetic metabolism in ENR animals, as evidenced by shifts in triglycerides and fatty acids, VLDL/LDL and creatine regions. The TLR2 gene showed to be downregulated in the jejunum of ENR pigs after weaning. The integration of gene expression, metabolome and microbiota datasets confirmed that differences between barren and enriched neonatal environments were evident only after weaning. Our results suggest that improvements in adaptation to weaning could be mediated by a better response to the post-weaning stress.

Efficacy of Paclitaxel Balloon for Hemodialysis Stenosis Fistulae After One Year Compared to High-Pressure Balloons: A Controlled, Multicenter, Randomized Trial.

PURPOSE: A controlled, prospective, multicenter, randomized trial to compare primary patency after angioplasty with a drug-coated balloon versus plain angioplasty balloon in stenosis of dysfunctional fistulae and grafts for hemodialysis. MATERIALS AND METHODS: A total of 136 patients (148 angioplasties) at four centers were randomized to receive a drug-coated balloon or plain angioplasty balloon after satisfactory angioplasty with a high-pressure balloon. The inclusion criteria were clinical signs of vascular dysfunction confirmed by Doppler Ultrasound and/or angiography. The primary endpoint was target lesion patency defined as time elapsed between the completion of effective and the appearance of restenosis at 6 and 12 months after angioplasty. Secondary endpoints included the relationship between the location of the stenosis, previous angioplasty, demographic variables and survival. RESULTS: Primary patency after angioplasty was higher in the group treated with the drug-coated balloon than the plain angioplasty balloon (153.01 to 141.69 days at 6 months; 265.78 to 237.83 days at 12 months). Drug-coated balloon angioplasty resulted in superior patency after 6 and 12 months, but this result was not statically significant (P = 0.068 at 6 months; P = 0.369 at 12 months). There was no relation between target lesion patency and the other variables studied. Overall mortality in the plain angioplasty balloon group was higher (9% vs. 5.7%) but not statistically significant. CONCLUSIONS: Drug-coated balloon angioplasty resulted in superior survival of dysfunctional peripheral vascular access at 6 and 12 months, but this result was not statistically significant. Both arms show equivalent complications and similar mortality. LEVEL OF EVIDENCE: Level Ia, therapeutic study, RCT. EBM ratings will be based on a scale of 1-5.

[Use of metaphyseal stems «Proxima¼ DePuy: our experience to more than five years]. / Utilización de los vástagos metafisarios «Próxima¼ DePuy: nuestra experiencia a más de cinco años.

The total hip arthroplasty with short stems to preserve bone is a good choice in young patients that expected future revision surgery, it is also a good choice when we use approaches for minimal invasive surgeries. In this study, we have evaluated, clinically and radiologically, our experience in total hip arthroplasty with the use of short stems and metaphyseal anchorage. In total we have involved 23 patients with a mean age of 50.2 years (range 45 to 69 y/o) at the time of surgery. The median follow-up was greater than five years. There was a slight Varus femoral stem in three cases, one of them in severe varus. The latter presented continuous pain in the lateral aspect of the thigh that increased with time, with a diaphyseal reaction and an increase in radiolucencies around the stem that required revision surgery 12 months postoperative. A longer follow-up is required to analyze the results and confirm the durability of the observed clinical findings. Patients were evaluated radiological and clinically using the scale of Merle dAubigné (MD).

La artroplastía total de cadera con los vástagos cortos encaminada a preservar el hueso es una buena opción en pacientes jóvenes a quienes se les prevé futuras cirugías de revisión. También es una buena elección cuando se utilizan cirugías con abordajes miniinvasivos. En este estudio clínico y radiológico hemos evaluado nuestra experiencia en el uso de artroplastía total de cadera con vástagos cortos de anclaje metafisario tipo DePuy Próxima. En total se han intervenido 23 pacientes con una edad media de 50.2 años (rango de 45 a 69 años) en el momento de la cirugía. El seguimiento medio fue de más de cinco años. Hubo un ligero varo del tallo femoral en tres casos, uno de ellos en varo severo. Este último caso presentó dolor continuo en las caras laterales del muslo que aumentó con el tiempo junto con una reacción diafisaria y un aumento en el tallo que requirió cirugía de revisión a los 12 meses postoperatorios. Se requiere un seguimiento más prolongado para analizar los resultados y confirmar la durabilidad de los resultados clínicos observados. Los pacientes fueron evaluados radiológica y clínicamente utilizando el baremo de Merle dAubigné (MD).

Utilización de los vástagos metafisarios «Próxima¼ DePuy: nuestra experiencia a más de cinco años / Use of metaphyseal stems «Proxima¼ DePuy: our experience to more than five years

Resumen: La artroplastía total de cadera con los vástagos cortos encaminada a preservar el hueso es una buena opción en pacientes jóvenes a quienes se les prevé futuras cirugías de revisión. También es una buena elección cuando se utilizan cirugías con abordajes miniinvasivos. En este estudio clínico y radiológico hemos evaluado nuestra experiencia en el uso de artroplastía total de cadera con vástagos cortos de anclaje metafisario tipo DePuy Próxima. En total se han intervenido 23 pacientes con una edad media de 50.2 años (rango de 45 a 69 años) en el momento de la cirugía. El seguimiento medio fue de más de cinco años. Hubo un ligero varo del tallo femoral en tres casos, uno de ellos en varo severo. Este último caso presentó dolor continuo en las caras laterales del muslo que aumentó con el tiempo junto con una reacción diafisaria y un aumento en el tallo que requirió cirugía de revisión a los 12 meses postoperatorios. Se requiere un seguimiento más prolongado para analizar los resultados y confirmar la durabilidad de los resultados clínicos observados. Los pacientes fueron evaluados radiológica y clínicamente utilizando el baremo de Merle d'Aubigné (MD).

Abstract: The total hip arthroplasty with short stems to preserve bone is a good choice in young patients that expected future revision surgery, it is also a good choice when we use approaches for minimal invasive surgeries. In this study, we have evaluated, clinically and radiologically, our experience in total hip arthroplasty with the use of short stems and metaphyseal anchorage. In total we have involved 23 patients with a mean age of 50.2 years (range 45 to 69 y/o) at the time of surgery. The median follow-up was greater than five years. There was a slight Varus femoral stem in three cases, one of them in severe varus. The latter presented continuous pain in the lateral aspect of the thigh that increased with time, with a diaphyseal reaction and an increase in radiolucencies around the stem that required revision surgery 12 months postoperative. A longer follow-up is required to analyze the results and confirm the durability of the observed clinical findings. Patients were evaluated radiological and clinically using the scale of Merle d'Aubigné (MD).

In silico analysis of the competition between Streptococcus sanguinis and Streptococcus mutans in the dental biofilm.

During dental caries, the dental biofilm modifies the composition of the hundreds of involved bacterial species. Changing environmental conditions influence competition. A pertinent model to exemplify the complex interplay of the microorganisms in the human dental biofilm is the competition between Streptococcus sanguinis and Streptococcus mutans. It has been reported that children and adults harbor greater numbers of S. sanguinis in the oral cavity, associated with caries-free teeth. Conversely, S. mutans is predominant in individuals with a high number of carious lesions. Competition between both microorganisms stems from the production of H2 O2 by S. sanguinis and mutacins, a type of bacteriocins, by S. mutans. There is limited evidence on how S. sanguinis survives its own H2 O2 levels, or if it has other mechanisms that might aid in the competition against S. mutans, nonetheless. We performed a genomic and metabolic pathway comparison, coupled with a comprehensive literature review, to better understand the competition between these two species. Results indicated that S. sanguinis can outcompete S. mutans by the production of an enzyme capable of metabolizing H2 O2 . S. mutans, however, lacks the enzyme and is susceptible to the peroxide from S. sanguinis. In addition, S. sanguinis can generate energy through gluconeogenesis and seems to have evolved different communication mechanisms, indicating that novel proteins may be responsible for intra-species communication.

Thyroid hormones are essential to preserve non-proliferative cells of adult neurogenesis of the dentate gyrus.

Thyroid hormones (THs) regulate adult hippocampal neurogenesis, a process that involves both cell populations that dynamically switch between pools of proliferative and quiescent cells, and cells that definitely leave the cell cycle to maturate into granular neurons. This investigation was carried out to determine the role of THs on the mitotic activity of specific proliferative cell populations and the preservation of non-proliferative cells participating in the neurogenic process of the dentate gyrus (DG) of the hippocampus. Hypothyroidism was induced in male adult Wistar rats with methimazole for 28days. We quantified the total number of proliferative cells (BrdU+), proliferative type 1 (BrdU+/GFAP+), and 2b and 3 (BrdU+/DCX+) cells. Early non-proliferative cells (BrdU-/DCX+ cells lacking dendritic process), postmitotic neuroblasts (Tuj 1+ cells lacking dendritic process), and immature granular neurons (IGN; DCX+ or Tuj 1+ and the presence of dendritic processes into granular or molecular layer) were also included. The evidence showed that the proliferation of Type 1, 2b and 3 cells is not modified by hypothyroidism. In contrast, hypothyroidism reduced the number of early non-proliferative cells and also leads to a decrement in the number of IGN. Our results show that proliferative cells of the DG are not sensitive to thyroid perturbations. However, THs are essential to preserve cell populations that leave the cell cycle in the DG of the hippocampus.

Surgical intestinal manipulation increases gene expression of TrkA, CGRP, and PAR-2 IN dorsal root ganglia in the rat.

BACKGROUND: Surgical handling of the bowel evokes degranulation of peritoneal mast cells (PMC). Nonetheless, role of PMCs in postoperative ileus (POI) is somewhat controversial. We aimed to investigate if intestinal manipulation elicits changes in afferent mediators related to MC activation and alteration of gastrointestinal (GI) motility. METHODS: Postoperative ileus was induced by intestinal manipulation in Sprague-Dawley rats. Additionally, compound 48/80 (C48/80) and ketotifen were used to modulate MC activity. Rat mast cell protease 6 (RMCP-6, ELISA) release was determined in peritoneal lavage 20 min after intestinal manipulation. At 24 h, GI transit was determined. Gene expression of calcitonin gene-related peptide (CGRP), protease-activated receptor-2 (PAR-2), nerve growth factor (NGF), and TrkA receptor was determined (PCR) in dorsal root ganglia (DRG). Ileal wall inflammation was assessed by myeloperoxidase (MPO) activity, interleukin-6 expression (IL-6). KEY RESULTS: Intestinal manipulation and exposure to C48/80-induced degranulation of PMCs delayed GI transit and up-regulated IL-6 and MPO activity. Intestinal manipulation, but not C48/80, up-regulated CGRP, PAR-2, and NGF/TrkA in DRGs. Ketotifen only improved gastric emptying and fecal output. Up-regulation of CGRP and TrkA expression in DRG was not prevented by ketotifen. CONCLUSIONS & INFERENCES: Postoperative ileus is accompanied by activation of CGRP, NGF-TrkA, and PAR-2 in DRGs. Our results suggest that these mediators could be a target in further POI studies in order to find new therapeutic targets for this medical condition.

Persistent alterations in colonic afferent innervation in a rat model of postinfectious gut dysfunction: Role for changes in peripheral neurotrophic factors.

BACKGROUND: Visceral hypersensitivity in the inflamed gut is related partly to the effects of peripheral neurotrophic factors (NTFs) on local afferent neurons. However, alterations in sensory afferents of distant areas remain unexplored. Using the Trichinella spiralis infection model, which causes a jejunitis, we investigated the remodeling of colonic afferents and the potential role of NTFs. METHODS: Rats were infected with T. spiralis. Inflammatory-like changes, mucosal mast cells (MMCs) dynamics, and expression of nerve growth factor and glial cell line-derived NTFs (glial cell-derived neurotrophic factor, artemin, and neurturin) were determined in the colon up to day 30 postinfection. Functional responses of colonic afferents were determined assessing changes in the expression of sensory-related markers in thoracolumbar (TL)/lumbosacral (LS) dorsal root ganglias (DRGs) following intracolonic capsaicin. KEY RESULTS: Trichinella spiralis induced an inflammatory-like response within the colon, partly resolved at day 30 postinfection, except for a persistent MMC infiltrate. While the jejunum of infected animals showed an up-regulation in the expression of NTFs, a transitory down-regulation was observed in the colon. Overall, T. spiralis effects on DRGs gene expression were restricted to a transient down-regulation of TPRV1. Stimulation with intracolonic capsaicin induced a down-regulation of TRPV1 levels in TL and LS DRGs, an effect enhanced in LS DRGs of infected animals, regardless the postinfection time considered. CONCLUSIONS & INFERENCES: During intestinal inflammation, spread morphological and functional alterations, including remodeling of visceral afferents, are observed outside the primary region affected by the insult. Similar mechanisms might be operating in states of widespread alterations of visceral sensitivity.

l-Theanine prevents carbon tetrachloride-induced liver fibrosis via inhibition of nuclear factor κB and down-regulation of transforming growth factor ß and connective tissue growth factor.

Here we evaluated the ability of L-theanine in preventing experimental hepatic cirrhosis and investigated the roles of nuclear factor-κB (NF-κB) activation as well as transforming growth factor ß (TGF-ß) and connective tissue growth factor (CTGF) regulation. Experimental hepatic cirrhosis was established by the administration of carbon tetrachloride (CCl4) to rats (0.4 g/kg, intraperitoneally, three times per week, for 8 weeks), and at the same time, adding L-theanine (8.0 mg/kg) to the drinking water. Rats had ad libitum access to water and food throughout the treatment period. CCl4 treatment promoted NF-κB activation and increased the expression of both TGF-ß and CTGF. CCl4 increased the serum activities of alanine aminotransferase and γ-glutamyl transpeptidase and the degree of lipid peroxidation, and it also induced a decrease in the glutathione and glutathione disulfide ratio. L-Theanine prevented increased expression of NF-κB and down-regulated the pro-inflammatory (interleukin (IL)-1ß and IL-6) and profibrotic (TGF-ß and CTGF) cytokines. Furthermore, the levels of messenger RNA encoding these proteins decreased in agreement with the expression levels. L-Theanine promoted the expression of the anti-inflammatory cytokine IL-10 and the fibrolytic enzyme metalloproteinase-13. Liver hydroxyproline contents and histopathological analysis demonstrated the anti-fibrotic effect of l-theanine. In conclusion, L-theanine prevents CCl4-induced experimental hepatic cirrhosis in rats by blocking the main pro-inflammatory and pro-fibrogenic signals.

Early constraints in sexual dimorphism: survival benefits of feminized phenotypes.

Sexual dimorphism (SD) has evolved in response to selection pressures that differ between sexes. Since such pressures change across an individual's life, SD may vary within age classes. Yet, little is known about how selection on early phenotypes may drive the final SD observed in adults. In many dimorphic species, juveniles resemble adult females rather than adult males, meaning that out of the selective pressures established by sexual selection feminized phenotypes may be adaptive. If true, fitness benefits of early female-like phenotypes may constrain the expression of male phenotypes in adulthood. Using the common kestrel Falco tinnunculus as a study model, we evaluated the fitness advantages of expressing more feminized phenotypes at youth. Although more similar to adult females than to adult males, common kestrel fledglings are still sexually dimorphic in size and coloration. Integrating morphological and chromatic variables, we analysed the phenotypic divergence between sexes as a measure of how much each individual looks like the sex to which it belongs (phenotypic sexual resemblance, PSR). We then tested the fitness benefits associated with PSR by means of the probability of recruitment in the population. We found a significant interaction between PSR and sex, showing that in both sexes more feminized phenotypes recruited more into the population than less feminized phenotypes. Moreover, males showed lower PSR than females and a higher proportion of incorrect sex classifications. These findings suggest that the mechanisms in males devoted to resembling female phenotypes in youth, due to a trend to increase fitness through more feminized phenotypes, may provide a mechanism to constrain the SD in adulthood.

Mast cell degranulation inhibits motor patterns of human ileum and sigmoid colon in vitro: relevance for postoperative ileus.

BACKGROUND: Local release of mast cell proteases during gastrointestinal surgery is associated with the inhibition of motility and postoperative ileus (POI). We determined whether activation of intramuscular mast cell affects the motor patterns of the human ileum and colon and whether proteases are involved. METHODS: Motor response of ileal and colonic circular muscle strips was measured in organ bath. Mast cell degranulation was induced by compound 48/80 (c48/80; 25-675 µg/mL). Motor response was quantified as tone, rhythmic phasic contractions (RPCs) and contractions to electric field stimulation (EFS; 40 Hz), and bethanechol-evoked contractions. Ketotifen (10(-6) mol/L) and a protease inhibitor cocktail (P8340) were used to evaluate the role of mast cell mediators. KEY RESULTS: (a) c48/80 impaired the spontaneous and the electrically evoked motor response in small bowel and colonic strips (sigmoid colon EC50 : 460.0 µg/mL for RPCs and 8.9 µg/mL for electrically evoked contraction amplitudes) and bethanechol-evoked contractions. (b) Preincubation with ketotifen (10(-6) mol/L, 1 h) prevented the impairment of RPCs and EFS-evoked contractions in the sigmoid colon and ileum but not in the right colon. (c) Preincubation with P8340 also prevented the impairment of contractions in the sigmoid colon but not in the ileum or the right colon. CONCLUSIONS & INFERENCES: Mast cell degranulation by c48/80 inhibits the spontaneous and the nerve-mediated motor response in the human ileum and colon. The effect is partially mediated by mast cell proteases and could be relevant in the pathophysiology of POI.

Peritoneal mast cell degranulation and gastrointestinal recovery in patients undergoing colorectal surgery.

BACKGROUND: Degranulation of peritoneal mast cells (MCs) induced by intestinal manipulation has been proposed as a pathophysiological factor in postoperative ileus (POI). We aimed to explore the relationship between peritoneal and colonic MC degranulation and gastrointestinal (GI) recovery following colectomy. METHODS: Patients undergoing elective laparoscopic cholecystectomy (using a laparoscope and small abdominal incisions, n = 14), and elective laparoscopic (n = 32) or open partial colectomy (through a large abdominal incision, n = 10) were studied. MC protease tryptase and chymase were studied in peritoneal fluid at the beginning, middle, and end of each surgical intervention. Density of MCs in colectomy samples were examined and oro-caecal transit time by breath test, GI function recovery by clinical composite endpoint GI-2 and association between MC proteases and clinical recovery. KEY RESULTS: Open and laparoscopic colectomy caused greater peritoneal release of tryptase and chymase (323.0 ng/mL [IQR: 53.05-381.4] and 118.6 ng/mL [IQR: 53.60-240.3]), than cholecystectomy (41.64 ng/mL [IQR: 11.17-90.93]) at the end of the surgical intervention. However, there were no differences between laparoscopic and open colectomy. Increased peritoneal protease release during surgery was observed in patients who developed POI after colectomy. CONCLUSIONS & INFERENCES: Colorectal surgery causes protease release from peritoneal MCs. Protease release does not differ between both types of colectomy (laparoscopy vs laparotomy). However, MC activation is increased in colectomy patients developing POI. Therefore, degranulation of peritoneal MCs as a factor contributing to human POI after colectomy might be considered in future studies as a target to avoid POI.

Ultrasound as predictor of histologic subtypes linked to recurrence in basal cell carcinoma of the skin.

BACKGROUND: Basal cell carcinoma (BCC) recurrences, especially in the facial region, represent a complex cosmetic problem. To date the possibility of predicting recurrence is supported solely by the histologic subtype. OBJECTIVE: To evaluate the relationship between BCC histologic subtypes linked to high and low risk of recurrence and the presence of hyperechoic spots on sonography. METHODS: Retrospective analysis of the pre-surgical ultrasound examinations of primary BCC tumours with visualization and counting of intra-tumoural hyperechoic spots. The data were then correlated with the corresponding histologic subtype. RESULTS: Thirty one patients with histologically proven BCC were included in the study. Hyperechoic spots were detected in all cases and there was a positive, statistically significant association between hyperechoic spots count and high recurrence risk histologic subtypes. Higher hyperechoic spots count was found in the recurrence-prone micronodular, sclerosing variant and morpheiform BCC subtypes. Low risk and high risk of recurrence showed a significant difference on the mean hyperechoic spots count of 5.5 (range: 3-25) and 8 (4-81). A cut-off point ≥7 hyperechoic spots presented a sensitivity of 79% and specificity of 53% for predicting the high risk of recurrence subtypes. CONCLUSION: The presence and count of hyperechoic spots within BCC lesions may help predicting the high risk of recurrence histologic subtypes.

Genetic basis and fitness correlates of dynamic carotenoid-based ornamental coloration in male and female common kestrels Falco tinnunculus.

Knowledge of the genetic basis of sexual ornaments is essential to understand their evolution through sexual selection. Although carotenoid-based ornaments have been instrumental in the study of sexual selection, given the inability of animals to synthesize carotenoids de novo, they are generally assumed to be influenced solely by environmental variation. However, very few studies have directly estimated the role of genes and the environment in shaping variation in carotenoid-based traits. Using long-term individual-based data, we here explore the evolutionary potential of a dynamic, carotenoid-based ornament (namely skin coloration), in male and female common kestrels. We first estimate the amount of genetic variation underlying variation in hue, chroma and brightness. After correcting for sex differences, the chroma of the orange-yellow eye ring coloration was significantly heritable (h2±SE=0.40±0.17), whereas neither hue (h2=0) nor brightness (h2=0.02) was heritable. Second, we estimate the strength and shape of selection acting upon chromatic (hue and chroma) and achromatic (brightness) variation and show positive and negative directional selection on female but not male chroma and hue, respectively, whereas brightness was unrelated to fitness in both sexes. This suggests that different components of carotenoid-based signals traits may show different evolutionary dynamics. Overall, we show that carotenoid-based coloration is a complex and multifaceted trait. If we are to gain a better understanding of the processes responsible for the generation and maintenance of variation in carotenoid-based coloration, these complexities need to be taken into account.

ESLAV/ECLAM/LAVA/EVERI recommendations for the roles, responsibilities and training of the laboratory animal veterinarian and the designated veterinarian under Directive 2010/63/EU.

Directive 2010/63/EU was adopted in September 2010 by the European Parliament and Council, and became effective in January 2013. It replaces Directive 86/609/EEC and introduces new requirements for the protection of animals used for scientific purposes. In particular, it requires that establishments that breed, supply or use laboratory animals have a designated veterinarian (DV) with expertise in laboratory animal medicine, or a suitably qualified expert where more appropriate, charged with advisory duties in relation to the well-being and treatment of the animals. This paper is a report of an ESLAV/ECLAM/LAVA/EVERI working group that provides professional guidance on the role and postgraduate training of laboratory animal veterinarians (LAVs), who may be working as DVs under Directive 2010/63/EU. It is also aimed at advising employers, regulators and other persons working under the Directive on the role of the DV. The role and responsibilities of the DV include the development, implementation and continuing review of an adequate programme for veterinary care at establishments breeding and/or using animals for scientific purposes. The programme should be tailored to the needs of the establishment and based on the Directive's requirements, other legislations, and current guidelines in laboratory animal medicine. Postgraduate laboratory animal veterinary training should include a basic task-specific training module for DVs to complement veterinary competences from graduation, and continuing professional development on the basis of a gap analysis. A tiered approach to further training in laboratory animal veterinary medicine and science offers career development pathways that are mutually beneficial to LAVs and establishments.

Metacarpophalangeal and interphalangeal joint arthrodesis: a comparative study between tension band and compression screw fixation.

A retrospective, comparative cohort study was performed of metacarpophalangeal or proximal interphalangeal joint arthrodesis with either tension band (n = 28) or compression (Acutrak Mini) screw (n = 29) methods. We compared rate of union, healing time, complications, and re-operation rate. Union was achieved in 26/28 (92.8%) of the tension band group (9.4 weeks) and 24/28 (85.7%) of the compression screw group (9.8 weeks). Only 28 patients in the screw group were assessed for union as one patient in the screw group sustained a fracture at the time of insertion and was converted to tension band fixation. The complication rate was 8/28 (28.6%) in the tension band group and 8/29 (27.6%) in the compression screw group. Re-operation rate was 9/28 (32.1%) in the tension band group and 1/29 (3.6%) in the compression screw group. Our findings indicate that bone healing, healing time, and complications are similar in both groups. The tension band technique had a significantly higher re-operation rate (hardware removal), but was the technique for salvage following failure of the screw technique.

Influence of land use and climate on the load of suspended solids in catchments of Andean rivers.

Understanding the interaction between anthropogenic land use and the rainfall pattern can be crucial to predict changes in total suspended solids (TSS) in streams and rivers. We assessed the effects of land use and annual rainfall on the TSS load of 19 southern Chilean catchments. The results indicated that the concentration of TSS increased in catchments with a rainy regime and greater annual precipitation. TSS load also increased as the surface of open areas increased at the catchment scale and decreased with increasing cover of glaciers and perennial snow. However, we did not find support for models with interaction terms between climate and land use. Results suggest that a regional decrease in annual rainfall accompanied by an increase in the altitude of the zero isotherms, as predicted by climate models, should have multiple effects on TSS. In particular, increased TSS load can be expected from a contraction of glaciers and perennial snow areas as well as the intensification of new crops and urban expansion.