Intestinal inflammation marker calprotectin regulates epithelial intestinal zinc metabolism and proliferation in mouse jejunal organoids.

Calprotectin (CP), a heterodimer of S100A8 and S100A9, is expressed by neutrophils and a number of innate immune cells and is used widely as a marker of inflammation, particularly intestinal inflammation. CP is a ligand for toll-like receptor 4 (TLR4) and the receptor for advanced glycation end products (RAGE). In addition, CP can act as a microbial modulatory agent via a mechanism termed nutritional immunity, depending on metal binding, most notably Zn2+. The effects on the intestinal epithelium are largely unknown. In this study we aimed to characterize the effect of calprotectin on mouse jejunal organoids as a model epithelium, focusing on Zn2+ metabolism and cell proliferation. CP addition upregulated the expression of the Zn2+ absorptive transporter Slc39a4 and of methallothionein Mt1 in a Zn2+-sensitive manner, while downregulating the expression of the Zn2+ exporter Slc30a2 and of methallothionein 2 (Mt2). These effects were greatly attenuated with a CP variant lacking the metal binding capacity. Globally, these observations indicate adaptation to low Zn2+ levels. CP had antiproliferative effects and reduced the expression of proliferative and stemness genes in jejunal organoids, effects that were largely independent of Zn2+ chelation. In addition, CP induced apoptosis modestly and modulated antimicrobial gene expression. CP had no effect on epithelial differentiation. Overall, CP exerts modulatory effects in murine jejunal organoids that are in part related to Zn2+ sequestration and partially reproduced in vivo, supporting the validity of mouse jejunal organoids as a model for mouse epithelium.

Mesh repair for lateral inguinal hernias: a non-evidence-based practice.

INTRODUCTION: The EHS clinical guidelines recommend the use of mesh to repair symptomatic primary inguinal hernias (PIH) in adult males but, in spite of this, it begs the question as to why there is still place for tissue techniques. Lack of stratification of patients according to risk of recurrence in RCTs might be a cause of results disparity, since medial and mixed are hernias with higher risk of recurrence (HRRH), whereas lateral hernias present a lower risk (LRRH). OBJECTIVE: To determine whether the lack of stratification may lead to questionable conclusions regarding the protective effect of mesh techniques and to identify other methodological flaws. METHODS: In the RCTs included in the clinical guidelines that addressed recurrences of PIH after mesh and non-mesh techniques, we assessed the type of hernias classification used, the number needed to treat in LRRH and HRRH and the statistical power. RESULTS: Most of trials were underpowered; five studies classified the hernia types; in the three studies that compared the recurrence rates of LRRH and HRRH the effect of mesh techniques was small; only two trials record data needed to calculate the NNT in LRRH (46 y 84 patients, respectively). CONCLUSION: The idea that mesh techniques reduce the recurrence rate in all PIHs is not supported by high level of evidence. The NNT for pure lateral hernias was very high and should be interpreted taking into account chronic pain rates and costs.

Synergistic mode of action of catechin, vanillic and protocatechuic acids to inhibit the adhesion of uropathogenic Escherichia coli on silicone surfaces.

AIMS: To study the individual and combined contribution of catechin, protocatechuic and vanillic acids to inhibit the adhesion of uropathogenic Escherichia coli (UPEC) on the surface of silicone catheters. METHODS AND RESULTS: The adhesion of UPEC to silicone catheters during the exposure to nonlethal concentrations of phenolic compounds was measured, as well as changes in motility, presence of fimbriae, extra-cellular polymeric substances, surface charge, hydrophobicity and membrane fluidity. The phenolic combination reduced 26-51% of motility, 1 log CFU per cm2 of adhered bacteria and 20-40% the carbohydrate and protein content in the biofilm matrix. Curli fimbriae, surface charge and cell hydrophobicity were affected to a greater extent by the phenolic combination. In the mixture, vanillic acid was the most effective for reducing bacterial adhesion, extra-polymeric substance production, motility, curli fimbriae and biofilm structure. Notwithstanding, protocatechuic acid caused major changes in the bacterial cell surface properties, whereas catechin affected the cell membrane functionality. CONCLUSION: Catechin, protocatechuic and vanillic acids have different bacterial cell targets, explaining the synergistic effect of their combination against uropathogenic E. coli. SIGNIFICANCE AND IMPACT OF STUDY: This study shows the contribution of catechin, protocatechuic and vanillic acids in producing a synergistic mixture against the adhesion of uropathogenic E. coli on silicone catheters. The action of catechin, vanillic and protocatechuic acids included specific contributions of each compound against the E. coli membrane's integrity, motility, surface properties and production of extracellular polymeric substances. Therefore, the studied mixture of phenolic compounds could be used as an antibiotic alternative to reduce urinary tract infections associated with silicone catheters.

Virulence of Pseudomonas aeruginosa exposed to carvacrol: alterations of the Quorum sensing at enzymatic and gene levels.

The main goal of this study was to evaluate the inhibition of Pseudomonas aeruginosa virulence factors and Quorum Sensing during exposure to carvacrol. P. aeruginosa (ATCC 10154) was exposed to carvacrol determining changes in biofilm development, motility, acyl-homoserine lactones (AHL) synthesis and relative expression of lasI/lasR. Docking analysis was used to determinate interactions between carvacrol with LasI and LasR proteins. P. aeruginosa produced 60% lower AHLs when exposed to carvacrol (1.9 mM) compared to control, without affecting cellular viability, indicating a reduction on the LasI synthase activity. AHL-C12, C6, and C4 were detected and related to biofilm development, motility, and pyocyanin production, respectively. The presence of carvacrol reduced the expression of lasR, without affecting lasI gen. Moreover, computational docking showed interactions of carvacrol with amino acids in the active site pocket of LasI (-5.6 kcal mol-1) and within the binding pocket of LasR (-6.7 kcal mol-1) of P. aeruginosa. These results demonstrated that virulence of P. aeruginosa was reduced by carvacrol, by inhibiting LasI activity with the concomitant reduction on the expression of lasR, biofilm and swarming motility. This study provides relevant information about the effect of carvacrol against quorum sensing to inhibit virulence factors of P. aeruginosa at enzymatic and gene levels. These findings can contribute to the development of natural anti-QS products, which can affect pathogenesis.

'Ripple' effect on infant zBMI trajectory of an internet-based weight loss program for low-income postpartum women.

BACKGROUND: Weight loss interventions can have positive 'ripple' effects on untreated partners in the home, but ripple effects on infants are unknown. OBJECTIVE: To examine whether a 12-month internet-based weight loss intervention for postpartum mothers had a positive ripple effect on participants' infants. METHODS: A 12-month cluster randomized, assessor-blind, clinical trial enrolling 371 postpartum women at 12 Women, Infants, Children clinics in CA. Clinics were randomized to standard Women, Infants, Children or an internet-based weight loss intervention for mothers. RESULTS: A total of 333 of the 371 (89.8%) mothers assented for infant participation. Infants were 5.3 ± 3.2 months; 75.9% were Hispanic and 64% were breastfeeding. Infant retention was 272/333 (82.7%) at 6 months post enrollment and 251/333 (75.3%) at 12 months post enrollment. In intent-to-treat analysis, a significant interaction between group and time was observed (p = 0.008) with the offspring of intervention mothers exhibiting lower zBMI change from study entry through 6 months (0.23 [CI, 0.03, 0.44] vs. 0.65 [0.50, 0.79] zBMI change, respectively; p = 0.001) but was not significant through 12 months (p = 0.16). Regardless of group, maternal reports at the final assessment indicated that infants (aged =17.2 ± 3.4 months) consumed sweetened beverages (0.93 ± 1.5/week), juice (2.0 ± 1.4/day), 'junk food' (7.8 ± 5.4/week) and fast food (2/month), and 46.7% of the infants had a TV in their bedroom. CONCLUSIONS: An internet-based weight loss program for low-income, postpartum mothers had a positive 'ripple' effect on the zBMI of infants in the home during the first 6 months of treatment.

Prenatal lead exposure in relation to age at menarche: results from a longitudinal study in Mexico City.

Animal and cross-sectional epidemiological studies suggest that prenatal lead exposure is related to delayed menarche, but this has not been confirmed in longitudinal studies. We analyzed this association among 200 girls from Mexico City who were followed since the first trimester of gestation. Maternal blood lead levels were analyzed once during each trimester of pregnancy, and daughters were asked about their first menstrual cycle at a visit between the ages of 9.8 and 18.1 years. We estimated hazard ratios (HRs) and 95% confidence intervals (CI) for probability of menarche over the follow-up period using interval-censored Cox models, comparing those with prenatal blood lead level ⩾5 µg/dl to those with prenatal blood lead <5 µg/dl. We also estimated HRs and 95% CI with conventional Cox regression models, which utilized the self-reported age at menarche. In adjusted analyses, we accounted for maternal age, maternal parity, maternal education, and prenatal calcium treatment status. Across trimesters, 36-47% of mothers had blood lead levels ⩾5 µg/dl. Using interval-censored models, we found that during the second trimester only, girls with ⩾5 µg/dl prenatal blood lead had a later age at menarche compared with girls with prenatal blood lead levels <5 µg/dl (confounder-adjusted HR=0.59, 95% CI 0.28-0.90; P=0.05). Associations were in a similar direction, although not statistically significant, in the conventional Cox regression models, potentially indicating measurement error in the self-recalled age at menarche. In summary, higher prenatal lead exposure during the second trimester could be related to later onset of sexual maturation.

Eclampsia como manifestación clínica de enfermedad trofoblástica gestacional: reporte de caso / Eclampsia as clinical presentation of gestational trophoblastic disease: case report

Introducción: La eclampsia es una complicación severa y poco frecuente del embarazo, apareciendo generalmente luego de las 34 semanas de edad gestacional. El diagnóstico de preeclampsia antes de las 20 semanas de edad gestacional se asocia con patología del trofoblasto. Presentación del caso: Paciente femenina de 18 años, 3 embarazos, 0 partos, 2 abortos, cursando embarazo de 14 semanas de edad gestacional, consulta por haber presentado síndrome convulsivo con crisis generalizadas de tipo tónico-clónicas y amaurosis posterior. Se sospecha síndrome de hipertensión endocraneana y se solicita resonancia magnética de encéfalo, que muestra múltiples lesiones córtico-subcorticales, sugiriendo síndrome de encefalopatía posterior reversible. Una ecografía obstétrica informa placenta aumentada de tamaño con múltiples imágenes econegativas con aspecto de panal de abeja, oligohidroamnios y feto con latidos positivos, sin anomalías anatómicas. La gonadotrofina coriónica humana fue de 11538440 U/L. Evoluciona con compromiso de conciencia y tres episodios de convulsión generalizada de tipo tónico-clónica con mala respuesta a diazepam y adecuada respuesta a sulfato de magnesio. Se pesquisa crisis hipertensiva y proteinuria de 24 horas de 8 gramos. Se decide interrupción del embarazo y manejo en Unidad de Paciente Crítico. Legrado aspirativo sin incidentes. La biopsia indica mola hidatidiforme parcial con feto sin malformaciones externas. Evolución favorable con negativización de gonadotrofina coriónica humana en controles posteriores. Discusión: El desarrollo de eclampsia antes de las 20 semanas es anecdótico con pocos casos reportados y su aparición debe hacer sospechar una patología del trofoblasto.

Introduction: Preeclampsia is a severe complication of pregnancy, usually appearing after 34 weeks of gestational age. The diagnosis of preeclampsia before 20 weeks of gestational age is associated with trophoblastic disease. Case report: Female patient, 18 years old, 3 pregnancies, 0 deliveries, 2 abortions, 14 weeks pregnant. Presents with generalized tonicclonic seizures and amaurosis. Clinical evaluation compatible with intracranial hypertension síndrome and magnetic resonance imaging of the brain is requested, showing multiple cortico-subcortical lesions, suggesting posterior reversible encephalopathy syndrome. Ultrasound evaluation informs increased size placenta, multiple echo-negativa images with honeycomb disposition, oligohydramnios and present fetal heartbeats. No fetal anatomic abnormalities. Human chorionic gonadotrophin level was 11538440 U/L. Clinical presentation evolves with impaired conscousness and three generalized tonic-clonic crisis, showing poor response to intravenous diazepam and appropriate response to magnesium sulfate. Hypertensive crisis develops and the result of 24 hour proteinuria is 8 grams. Due to mater nal risk pregnancy was interrupted and uterine aspirage was performed. Patient was managed in the Intensive Care Unit. Biopsy informed partial hydatidiform mole and fetus with no anatomical abnormalities. Clinical evolution was positive and human chorionic gonadotrophin level below detection during follow-up. Discussion: Development of eclapsia before 20 weeks of gestational age is anecdotal with few reported cases and could be indicative of gestational trophoblastic disease.

Esteatosis hepatica aguda en el tercer trimestre de embarazo gemelar: reporte de caso / Acute hepatic esteatosis during third trimester twin pregnancy: case report

Introducción: La esteatosis hepática aguda del embarazo (EHAE) es una patología metabólica grave e infrecuente caracterizada por esteatosis hepática microvesicular que conduce a insuficiencia hepática aguda. Aparece generalmente en el tercer trimestre de gestación y se reconoce el embarazo gemelar como un factor de riesgo para su desarrollo. Presentación del caso: Paciente femenina de 25 años sin antecedentes médicos, 2 embarazos, 1 parto y 0 abortos, cursando embarazo gemelar de 31 semanas de gestación, consultó por presentar cuadro de dolor abdominal, vómitos e ictericia. Se sospechó hepatitis aguda y se decidió hospitalizar. Al ingreso una ecografía obstétrica precisó latidos fetales ausentes decidiéndose interrupción del embarazo de urgencia. La paciente evolucionó con síndrome confusional y epistaxis masiva requiriendo transfusión. Exámenes de ingreso evidenciaron insuficiencia renal, insuficiencia hepática y trombocitopenia. Ingresó a Unidad de Paciente Crítico con diagnóstico de síndrome de HELLP requiriendo soporte con ventilación mecánica. Persistió con mala evolución clínica por lo que se solicitó tomografía de abdomen y pelvis mostrando signos de pancreatitis aguda y hematoma subcapsular hepático. Exámenes de control objetivaron hiperbilirrubinemia, transaminasas elevadas, hipoalbuminemia, hipocolesterolemia y tiempo de protrombina elevado. Se planteó diagnóstico de esteatosis hepática aguda del embarazo. Ingresó a lista de espera para trasplante hepático. Posteriormente evolucionó con mejoría espontánea de la función hepática y se logró extubar tras dos semanas de hospitalización. Discusión: El desarrollo de esteatosis hepática aguda del embarazo es infrecuente y potencialmente grave debiéndose interrumpir el embarazo precozmente y manejarse en unidades de paciente crítico debido a su alta mortalidad.

Introduction: Acute hepatic esteatosis of pregnancy (AHEP) is a serious and uncommon metabolic pathology characterized by microvesicular liver steatosis leading to acute liver failure. It usually appears in the third trimester of gestation and twin pregnancy is recognized as a risk factor for its development. Case Report: A 25-year-old female patient with no medical history, 2 pregnancies, 1 childbirth and 0 abortions, having a twin pregnancy of 31 weeks' gestation, consulted for abdominal pain, vomiting and jaundice. Acute hepatitis was suspected and it was decided to hospitalize. On admission, an obstetric ultrasonography screened for absent fetal beats, deciding to interrupt the pregnancy. The patient evolved with confusional syndrome and massive epistaxis requiring transfusion. She presented renal failure, hepatic failure, and thrombocytopenia. He entered a Critical Patient Unit with diagnosis of HELLP syndrome requiring support with mechanical ventilation. It persisted with poor clinical evolution, requiring tomography of the abdomen and pelvis showing signs of acute pancreatitis and subcapsular hepatic hematoma. Control examinations aimed at hyperbilirubinemia, elevated transaminases, hypoalbuminemia, hypocholesterolemia and elevated prothrombin time. A diagnosis of acute fatty liver of pregnancy was made. He entered the waiting list for liver transplantation. Subsequently it evolved with spontaneous improvement of the liver function and was able to extubate after two weeks of hospitalization. Discussion: The development of acute fatty liver of pregnancy is infrequent and potentially serious due to early termination of pregnancy and management in critical patient units due to its high mortality.

Molecular analysis of complex cases of alpha- and beta-thalassemia in Mexican mestizo patients with microcytosis and hypochromia reveals two novel alpha(0) -thalassemia deletions - -(Mex1) and - -(Mex2).

INTRODUCTION: Alpha-thalassemia (α-thal) is a common monogenic disorder worldwide. In mixed ethnic populations, α-thal and beta-thalassemia (ß-thal) can be expected, sometimes giving complex phenotypes, which without molecular analysis are not easily explained. We performed the molecular identification of α- and ß-thal alleles in 51 Mexican patients with microcytosis, hypochromia, and normal or low levels of HbA2 . METHODS: Common deletional alleles (-α(3.7) , -α(4.2) , - -(SEA) , - -(MED) , - -(FIL) , - -(THAI) , -α(20.5) ) and α-triplication were studied by gap-PCR and nondeletional alleles (α(IVSI) ((-5nt)) , α2 (NcoI) , α1 (NcoI) ) by ARMS. ß-thal alleles Cd39 (C>T), IVS1:1 (G>A), IVS1:110 (G>A), and Spanish δß-thal were also investigated. DNA sequencing was performed on HBA2, HBA1, and HBB genes. Negative samples were subjected to MLPA. RESULTS: In 35 subjects, we identified the mutations, -α(3.7) , - -(SEA) , - -(FIL) , α(IVSI) ((-5nt)) , and ααα(anti3.7) and two novel deletion alleles - -(Mex1) (6.8-8.9 kb) and - -(Mex2) (77.6-135.7 kb). Four individuals also had a ß-thal allele (Cd39/IVS1:110). No α-thal alleles were observed in 16 subjects, but three had a ß-thal mutation Cd39, IVS1:110, and Spanish δß-thal. CONCLUSION: α-thal is relatively common in Mexican patients, the combination with ß-thal is sometimes unexpected, and this underlines the importance of performing molecular analysis for both α- and ß-genes defects in patients showing microcytic hypochromic anemia.

The Americleft Project: A Comparison of Short- and Longer-Term Secondary Alveolar Bone Graft Outcomes in Two Centers Using the Standardized Way to Assess Grafts Scale.

OBJECTIVE: To compare length of follow-up and cleft site dental management on bone graft ratings from two centers. DESIGN: Blind retrospective analysis of cleft site radiographs and chart reviews for determination of cleft-site lateral incisor management. PATIENTS: A total of 78 consecutively grafted patients with complete clefts from two major cleft/craniofacial centers (43 from Center 1 and 35 from Center 2). INTERVENTIONS: Secondary iliac crest alveolar bone grafting, at a mean age of 9 years 9 months (Center 1: 9 years 7 months; Center 2: 10 years 0 month). MAIN OUTCOME MEASURES: The Americleft Standardized Way to Assess Grafts scale from 0 (failed graft) to 6 (ideal) was used to rate graft outcome at two time points (T1, T2). Average T1 was 11 years 1 month of age, 1 year 3 months postgraft. Average T2 was 17 years 11 months of age, 8 years 0 months postgraft. Six trained and calibrated raters scored each radiograph twice. Reliability was calculated at T1 and T2 using weighted kappa. A paired Wilcoxon signed rank test (P < .05) tested T1 and T2 differences for each center. A Kruskal-Wallis test was used to determine the significance of differences between centers at T1 and T2. Correlation tested whether T1 ratings predicted T2. Linear regression determined possible factors that might contribute to graft rating changes over time. RESULTS: Reliability was good at T1 and T2 (interrater = .713 and .701, respectively; intrarater = .790 and .805, respectively). Center 1 scores were significantly better than those from Center 2 at both T1 (5.21 versus 3.29) and T2 (5.18 versus 3.44). There was no statistical difference between T1 and T2 scores for either center; although, there was a greater chance of bone graft score improving with completion of canine eruption and substitution for missing lateral incisors. CONCLUSIONS: Short-term ratings of graft outcomes identified significant differences between centers that persisted over time. Dental cleft-site management influenced final graft outcome.

The Americleft Project: A Proposed Expanded Nasolabial Appearance Yardstick for 5- to 7-Year-Old Patients With Complete Unilateral Cleft Lip and Palate (CUCLP).

OBJECTIVE: To develop a yardstick of reference photographs for nasolabial appearance assessments of 5- to 7-year-old patients with complete unilateral cleft lip and palate (CUCLP). DESIGN: Blind retrospective analysis of clinical records and comparison to historical controls. PATIENTS: Subjects were two groups of 6- to 12-year-olds (n = 124 and n = 135) and one group of 5- to 7-year-olds (n = 149) with nonsyndromic CUCLP from three previous Americleft studies, including cohorts from seven different cleft/craniofacial centers. INTERVENTIONS: All patients received the infant management protocols of their respective centers. Eleven trained and calibrated judges (five participated in all three studies) did blind ratings of nasolabial appearance using the Asher-McDade method. MAIN OUTCOME MEASURES: Patients receiving the most consistent ratings between judges, selected first from the groups of 6- to 12-year-olds, were used to create a pilot yardstick for eventual use in the third study of 5- to 7-year-olds. For each of the Asher-McDade categories, 8 of the 5- to 7-year-old patients receiving the most consistent scores between raters were ranked by 10 judges for a final elimination to leave three per category. RESULTS: Using this method of successive changes in rating methods, a new reference yardstick for nasolabial appearance rating was established and linked to the original Asher-McDade method as well as the single examples in a previously published yardstick for patients with CUCLP. Pilot testing using the yardstick improved reliabilities. CONCLUSIONS: Use of an expanded nasolabial yardstick of reference photographs representative of the range of possibilities of each of the five Asher-McDade categories is now available to see if reliability of these ratings can be improved.

Comparación entre cirugía retrógrada intrarrenal y litotricia extracorpórea para el tratamiento de la litiasis de polo inferior renal de hasta 15 mm. Estudio prospectivo aleatorizado / Comparison between retrograde intrarenal surgery and extracorporeal shock wave lithotripsy in the treatment of lower pole kidney stones up to 15 mm. Prospective, randomized study

Introducción: La litrotricia extracorpórea (LEC) es el tratamiento más recomendado para la litiasis renal menor de 2 cm. Sin embargo, las bajas tasas libre de cálculos (SFR) en litiasis de polo renal inferior hace plantear nuevas técnicas que ofrezcan mejores resultados, como la cirugía intrarrenal retrógrada (CRIR). Objetivo: Comparar la eficacia del tratamiento con LEC vs la CRIR en términos de SFR postratamiento en pacientes con litiasis renal de polo inferior de menos de 15 mm. Material y métodos: Se realizó un estudio prospectivo aleatorizado para evaluar los resultados de LEC y CRIR en pacientes portadores de litiasis renal de polo inferior menor a 15 mm. De un total de 55 pacientes en 31 se realizaron LEC (grupo 1) y 24 CRIR (grupo 2). Se evaluó el tamaño de la litiasis, lateralidad, tiempo operatorio, complicaciones de las técnicas según escala de Clavien, SFR y litiasis residuales a los 2 meses evaluado por tomografía computarizada de abdomen y pelvis sin contraste. Se realizó análisis estadístico para comparar las variables utilizando el programa Stata 11. Resultados: Los grupos no mostraron diferencias significativas en sus características generales, a excepción del tiempo operatorio (mayor para CRIR). CRIR mostró tener mayor proporción de SFR y de litiasis menor de 3 mm. Además CRIR mostró menor tasa de litiasis clínicamente significativa, siendo esta asociación estadísticamente significativa (0% vs 42,3%; p < 0,05). En el subgrupo de pacientes con litiasis entre 10 y 15 mm CRIR presento mayor SFR (75% vs 41,2%) y menor tasa de litiasis clínicamente significativa (0% vs 58,8%), alcanzando significación estadística (valor de p < 0,05). No se registraron complicaciones perioperatorias Clavien III o mayores para ambas técnicas. Conclusiones: En el tratamiento de litiasis de polo inferior CRIR mostró globalmente resultados de SFR similares a LEC y una menor tasa de litiasis residual clínicamente significativa, más aún en el subgrupo de pacientes con litiasis entre 10 y 15 mm, que mostró mejor SFR y mejor tasa de litiasis residual clínicamente significativa. Se requiere un mayor tamaño muestral para confirmar este resultado

Introduction: Extracorporeal Shock Wave Lithotripsy (ESWL) is currently the recommended treatment for intra-renal calculi smaller than 2 cm. However the low Stone Free Rate (SFR) in lower pole calculi gives rise to new techniques, such us retrograde intrarenal surgery (RIRS), for improve the surgery outcomes. Objective: To compare the efficacy of a treatment with ESWL with RIRS, in terms of SFR after surgery, in patients with kidney stones up to 15 mm in the lower pole. Material and methods: A prospective study was carried out in order to assess the results of ESWL and RIRS in patients with lower pole stones less than 15 mm. Among a total of 55 patients, 31 were underwent to ESWL (Group 1) and the remaining 24 to RIRS (Group 2). Clinical data recorded, including general characteristics of each patient, were: calculi size, side, operative time, complications according to Clavien scale, SFR and the presence of residual fragments at 2 months post-treatment assessed by a CT scan. STATA 11 was used to perform the statistical analysis. Results: There were no differences for general descriptors among groups with the exception of a significantly longer operative time for RIRS. The rates of SFR and residual fragments lesser than 3 mm. were lower in the RIRS group than in ESWL ones. RIRS also showed a lower rate of clinically significant fragments (0% vs 42.3%. P < .05). In the subgroup of patients with stones between 10/15 mm RIRS showed higher SFR (75% vs. 41.2%) and a lower rate of stones > 3 mm (0% vs. 58.8%), being statistically significant (P < .05). Clavien III or higher complications were not reported in any of the groups. Conclusions: In the treatment of lower pole stone RIRS has the same results than ESWL in terms of SFR. Regarding absence of a clinically significant residual fragment, RIRS was superior to ESWL. A bigger sample size is required in order to confirm this results

Influence of a flooding dose of valine on key indicators of metabolic status in the growing pig.

A key concern with the flooding dose technique for measuring protein synthesis is that a large dose of amino acid (AA) can potentially change the animals' hormonal and nutritional status, which in turn can influence protein synthesis. Among stable isotope tracers, 1-[(13)C]-valine is the preferred AA for measuring protein synthesis in gut tissue and mucins. A study was conducted to determine the impact of a flooding dose of valine on the metabolic status of pigs. Six barrows [16.5 kg body weight (BW)] were randomly assigned to intravenous infusions of either 150 mM valine (1.5 mmol/kg BW) or physiological saline, following a crossover design. Blood samples were taken 10 min prior to infusion, at the end of infusion, at 10-min intervals for 60 min post-infusion, and at 90 and 120 min post-infusion. Plasma concentrations of insulin, glucose, AA, urea nitrogen and packed cell volume (PCV) were measured. Infusion of valine increased plasma valine concentrations (4129 vs. 582 µM; P < 0.05) but had no influence on PCV (26.4% vs. 27.2%) and plasma concentrations of glucose (6.0 vs. 5.8 mM) and insulin (8.2 vs. 8.5 µU/ml; P > 0.10). Plasma urea nitrogen concentration was reduced with valine infusion (8.5 vs. 7.8 mg/dl; P < 0.05). A flooding dose of valine had no impact on plasma concentrations of AA, and specifically branched-chain AA such as leucine (240 vs. 231 µM) and isoleucine (310 vs. 331 µM; P > 0.10). There was, however, a slight increase in the plasma concentrations of threonine (224 vs. 263 µM; P < 0.05) and a tendency towards reduced glycine (1387 vs. 1313 µM; P < 0.10). The results indicate that a flooding dose of valine does not cause a substantial change in the metabolic status of growing pigs and is therefore suitable for measuring protein synthesis rates.

Comparison between retrograde intrarenal surgery and extracorporeal shock wave lithotripsy in the treatment of lower pole kidney stones up to 15 mm. Prospective, randomized study.

INTRODUCTION: Extracorporeal Shock Wave Lithotripsy (ESWL) is currently the recommended treatment for intra-renal calculi smaller than 2 cm. However the low Stone Free Rate (SFR) in lower pole calculi gives rise to new techniques, such us retrograde intrarenal surgery (RIRS), for improve the surgery outcomes. OBJECTIVE: To compare the efficacy of a treatment with ESWL with RIRS, in terms of SFR after surgery, in patients with kidney stones up to 15 mm in the lower pole. MATERIAL AND METHODS: A prospective study was carried out in order to assess the results of ESWL and RIRS in patients with lower pole stones less than 15 mm. Among a total of 55 patients, 31 were underwent to ESWL (Group 1) and the remaining 24 to RIRS (Group 2). Clinical data recorded, including general characteristics of each patient, were: calculi size, side, operative time, complications according to Clavien scale, SFR and the presence of residual fragments at 2 months post-treatment assessed by a CT scan. STATA 11 was used to perform the statistical analysis. RESULTS: There were no differences for general descriptors among groups with the exception of a significantly longer operative time for RIRS. The rates of SFR and residual fragments lesser than 3 mm. were lower in the RIRS group than in ESWL ones. RIRS also showed a lower rate of clinically significant fragments (0% vs 42.3%. P < .05). In the subgroup of patients with stones between 10/15 mm RIRS showed higher SFR (75% vs. 41.2%) and a lower rate of stones>3 mm (0% vs. 58.8%), being statistically significant (P < .05). Clavien III or higher complications were not reported in any of the groups. CONCLUSIONS: In the treatment of lower pole stone RIRS has the same results than ESWL in terms of SFR. Regarding absence of a clinically significant residual fragment, RIRS was superior to ESWL. A bigger sample size is required in order to confirm this results.

The effects of lip revision surgery on nasolabial esthetics in patients with cleft lip.

OBJECTIVES: 1) To determine the concordance among surgeons on subjective assessments of nasolabial esthetics in children with repaired cleft lip; and 2) to evaluate longitudinal changes in nasolabial esthetics in relation to cleft lip revision surgery. SETTING AND SAMPLE POPULATION: School of Dentistry at University of North Carolina, Chapel Hill. Children with repaired unilateral cleft lip: 32 had lip revision surgery and 27 did not have surgery. MATERIALS AND METHODS: Retrospective observational study from a non-randomized clinical trial. Ratings of nasolabial esthetics performed by six surgeons using the Asher-McDade scale at baseline and 12-month follow-up. RESULTS: Concordance among surgeons ranged from poor to acceptable. Nasolabial ratings at follow-up were better in the Revision group than in the Non-Revision group, although differences were small. The most prevalent change in the Revision Group was improvement in one or more units on the scale, while 'no change' was most prevalent in the Non-Revision group. Participants in the Revision group were more likely to receive a 'no' in relation to the need for lip or nose revision at the follow-up visit. CONCLUSION: There were mild esthetic improvements observed in relation to lip revision surgery, which should be interpreted with caution given the subjectivity of the rating method used.

Oregano essential oil-pectin edible films as anti-quorum sensing and food antimicrobial agents.

Edible films can be used as carriers for antimicrobial compounds to assure food safety and quality; in addition, pathogenesis of food bacteria is related to a cell to cell communication mechanism called quorum sensing (QS). Oregano essential oil (OEO) has proved to be useful as food antimicrobial; however, its food applications can be compromised by the volatile character of its active constituents. Therefore, formulation of edible films containing OEO can be an alternative to improve its food usages. QS inhibitory activity of OEO and pectin-OEO films was evaluated using Chromobacterium violaceum as bacterial model. Additionally, antibacterial activity was tested against Escherichia coli O157:H7, Salmonella Choleraesuis, Staphylococcus aureus, and Listeria monocytogenes. OEO was effective to inhibit bacterial growth at MIC of 0.24 mg/mL for all tested bacteria and MBC of 0.24, 0.24, 0.48, and 0.24 mg/mL against E. coli O157:H7, S. Choleraesuis, S. aureus, and L. monocytogenes, respectively. Pectin-films incorporated with 36.1 and 25.9 mg/mL of OEO showed inhibition diameters of 16.3 and 15.2 mm for E. coli O157:H7; 18.1 and 24.2 mm for S. Choleraesuis; 20.8 and 20.3 mm for S. aureus; 21.3 and 19.3 mm for L. monocytogenes, respectively. Pectin-OEO film (15.7 mg/mL) was effective against E. coli O157:H7 (9.3 mm), S. aureus (9.7 mm), and L. monocytogenes (9.2 mm), but not for S. Choleraesuis. All concentrations of OEO (0.0156, 0.0312, 0.0625 and 0.125 mg/mL) and pectin-OEO films (15.7, 25.9 and 36.1 mg/mL) showed a significant anti-QS activity expressed as inhibition of violacein production by C. violaceum. Additionally, the application of pectin-OEO films was effective reducing total coliforms, yeast, and molds of shrimp and cucumber slices stored at 4°C during 15 d. These results demonstrated the potential of pectin films enriched with OEO as food related microorganisms and QS inhibitors.

Modulación del metabolismo de esfingolípidos en cáncer de vejiga como una potencial estrategia para optimizar resultados de terapias intravesicales para tumores de vejiga no musculoinvasores / Modulation of sphingolipid metabolism in bladder cancer as a potential strategy to optimize outcomes of intravesical therapies for non-muscle invasive bladder cancers

El cáncer de vejiga representa un problema de salud pública importante a nivel mundial. En Chile su relevancia es aún mayor en la región de Antofagasta. Este cáncer se caracteriza por una alta tasa de recurrencia, por lo que los pacientes requieren un seguimiento estricto que afecta su calidad de vida e implica elevados costos para los sistemas de salud. Esto explica la necesidad de optimizar los tratamientos actuales (quimioterapia e inmunoterapia con BCG intravesical) para reducir las tasas de recurrencia y progresión. Los esfingolípidos son lípidos bioactivos que a nivel celular cumplen funciones relacionadas con la regulación del crecimiento, proliferación, migración, invasión, resistencia a drogas y apoptosis. La evidencia disponible a la fecha sobre el rol de los esfingolípidos en cáncer de vejiga es escasa, pero sugiere que en este cáncer existe un metabolismo esfingolipídico desplazado hacia la reducción de los niveles intracelulares de ceramida y esfingosina (esfingolípidos pro-apoptóticos) y aumento de esfingosina 1-fosfato (esfingolípido anti-apoptótico). La manipulación del metabolismo esfingolipídico para invertir esta relación se propone en esta revisión como una estrategia que podría ayudar a optimizar el efecto de las terapias disponibles actualmente para reducir las recurrencias y progresiones de los tumores de vejiga no músculo-invasores...

Bladder cancer is an important health problem worldwide. In Chile it has particular relevance in the region of Antofagasta. This cancer is characterized by a high recurrence rate, for which patients need a strict follow up that impairs their quality of life and determines increased costs for health care systems. These facts explain the necessity of optimizing the actual treatments (chemotherapy and BCG immunotherapy) for reducing the rates of recurrence and progression. Sphingolipids are bioactive lipids that at a cellular level have roles related to the regulation of growth, proliferation, migration, invasiveness, drug resistance and apoptosis. To date, the available evidence about the role of sphingolipids in bladder cancer is scarce, but suggests that in this cancer there is a sphingolipid metabolism shifted towards a reduction of the intracellular levels of ceramide and sphingosine (pro-apoptotic sphingolipids) and an increase of sphingosine 1-phosphate (anti-apoptotic sphingolipid). In this review we propose that the manipulation of the sphingolipid metabolism to invert this balance can contribute to optimize the effect of the actual therapies to reduce the rates of recurrence and progression of non-muscle invasive bladder cancers...

Association analysis of vitamin D receptor gene polymorphisms and bone mineral density in postmenopausal Mexican-Mestizo women.

We investigated associations between vitamin D receptor (VDR) gene polymorphisms, FokI T>C (rs2228570), BsmI G>A (rs1544410), ApaI G>T (rs7975232), and TaqI T>C (rs731236), with bone mineral density (BMD) in postmenopausal Mexican-Mestizo women. Three hundred and twenty postmenopausal women participated, who were classified according to World Health Organization criteria as non-osteoporotic (Non-OP; N = 88), osteopenic (Opn; N = 144), and osteoporotic (OP; N = 88). BMD measurements at the lumbar (L1-L4) spine and at the left and right femoral neck were obtained by dual-energy X-ray absorptiometry. Single nucleotide polymorphisms (SNPs) were genotyped using real-time polymerase chain reaction and TaqMan probes. Genotype and allelic frequencies of the 4 VDR SNPs were similar among the 3 groups. Polymorphic allele frequencies were as follows: FokI (C) 0.53, 0.49, 0.56; BsmI (A) 0.26, 0.22, 0.23; ApaI (T) 0.43, 0.39, 0.44; TaqI (C) 0.27, 0.22, 0.23 for the Non-OP, Opn, and OP groups, respectively. Although no associations were found between the SNPs and BMD, based on the putative function of the FokI SNP, we constructed, for the first time, the haplotype with the 4 VDR SNPs, and found that the CGGT haplotype differed between the Non- OP and OP groups (21.8 vs 31.8%, P < 0.05). The risk analysis for this haplotype was nearly significant under the dominant model (OR = 1.783, 95%CI = 0.98-3.25, P = 0.058). This result suggests a possible susceptibility effect of the C allele of the FokI SNP for the development of osteoporosis in postmenopausal Mexican-Mestizo women.

Esfingosina-1-fosfato y cánceres urológicos: identificando potenciales blancos terapéuticos en su etabolismo y señalización / Sphingosine-1-phosphate and urological cancers: identifying potential therapeutic targets in its metabolism and signalling

Los lípidos no sólo son moléculas estructurales de las membranas. Hay numerosos ejemplos de lípidos que median acciones fisiológicas dentro de las células. Específicamente, esfingolípidos como ceramida, esfingosina y esfingosina-1-fosfato (S1P) han sido involucrados en el control del crecimiento celular, la proliferación y la migración, todo lo cual se ha relacionado con el cáncer.Los efectos pro-apoptóticos de la ceramida y la esfingosina son revertidos por S1P. Por lo tanto, el destino de la célula puede ser modulada mediante el cambio de la proporción de estos esfingolípidos (el modelo reóstato). S1P promueve la proliferación celular, el crecimiento, la supervivencia, la migración, invasión y resistencia fármacos y radiación, en parte a través de receptores de membrana (S1PR1-5). La sobreexpresión de enzimas productoras de S1P y el aumento de los niveles de S1P se ha descrito en muchos tipos de cáncer, incluyendo cánceres urológicos. Por lo tanto, se pueden identificar posibles objetivos terapéuticos en el metabolismo y las vías de señalización de los esfingolípidos, cuya relevancia clínica debe ser determinada en futuros estudios.

Lipids are not only structural molecules of the membranes. There are numerous examples of lipids mediating physiologic actions within the cells. Specifically, sphingolipids like ceramide, sphingosine and sphingosine-1-phosphate (S1P) have been described to be involved in the control of cell growth, proliferation and migration, all of which has been linked to cancer. The pro-apoptotic effects of ceramide and sphingosine are opposed by S1P. Therefore, the fate of the cell can be modulated by changing the ratio of these sphingolipids (the rheostat model). S1P promotes cell proliferation, growth, survival, migration, invasion and resistance to drugs and radiation, in part mediated by S1P membrane receptors (S1PR1-5). Overexpression of S1P producing enzymes and increased S1P levels has been described in many cancers, including urological cancers. Therefore, potential therapeutic targets can be recognized in the metabolism and signaling pathways of sphingolipids and their clinical relevance have to be determined in future studies.

Esteroides androgénicos anabolizantes: consecuencias en el hombre / Anabolic androgenic steroids: consequences in the man

El abuso de Esteroides Androgénicos Anabolizantes (EAA) se ha convertido en una práctica frecuente en hombres. Deportistas de alto rendimiento y fisicoculturistas eran los usuarios más frecuentes de este tipo de fármacos, sin embargo, en los últimos 10 años se ha observado una preocupante prevalencia de abuso en hombres jóvenes y usuarios de gimnasios con el fin simplemente de mejorar su aspecto físico. Muchas veces este tipo de fármacos son adquiridos al margen de la legalidad, promocionados en internet, sin la supervisión médica, necesaria al sostener una terapia hormonal. La autoadministración de EAA en altas dosis guarda implicancias negativas poco conocidas o inadvertidas por lo usuarios. Dentro de estas destacan las consecuencias andrológicas propias del abuso de estas sustancias como son la disfunción sexual, alteraciones reproductivas, metabólicas y psicógenas. El objetivo de esta revisión es acercar el conocimiento actual sobre los riesgos e implicancias en el hombre del abuso de los EAA.

Anabolic Androgenic Steroid (EAA) Abuse has turned into a common practice upon men. High performance sportsmen and body builders were the most common users of these drugs, but in the last 10 years there has been a worrying prevalence of abuse in young men and fitness studio users with the aim of obtaining better physical aspect. Many times these drugs are bought at the margins of legality, promoted in Internet, without the medical supervision needed for hormonal therapy. Self-administration of EAA in high doses has negative effects that may be not known or unnoticed by users. Some of them are Sexual Dysfunction, reproductive, metabolic or psychological alterations. The purpose of this revision is to come closer to today’s knowledge of the risks of abuse of EAA in men.