Digital single-operator video cholangioscopy in treating refractory biliary stones: a multicenter observational study.

BACKGROUND: Standard endoscopic treatment might fail to treat biliary stone disease. Here, we investigated the efficacy and safety of recently introduced digital single-operator video cholangioscopy (SOVC) for the treatment of difficult biliary stones. METHODS: Digital SOVC procedures, performed in two tertiary referral centers between 2015 and 2018, were retrospectively analyzed. Only patients with a previous failure of endoscopic standard treatment and a SOVC-based biliary stone treatment using electrohydraulic lithotripsy (EHL) or laser lithotripsy (LL) were included. The primary endpoint was to evaluate the stone removal rate per procedure and per patient. RESULTS: In total, 75 examinations with a digital SOVC-assisted biliary stone treatment, performed in 60 patients, were identified. Biliary stones were mainly located extrahepatic (64%) and less frequently intrahepatic (36%). The median stone size was 20 mm (interquartile range [IQR]: 10-25 mm) and the median stone number was 1 (IQR: 1-2). Digital SOVC-based treatment of biliary stone disease was successful in 95% of patients and 15% needed at least two treatment sessions. Evaluated per procedure, a complete stone removal was accomplished in 67% of all examinations (including initial and repeated procedures), while an incomplete stone removal was observed in 33% of cases. The per procedure analyzes revealed that the success rates for a complete stone removal were similar between LL and EHL (66% vs. 68%; p = 0.87). Complications, such as postinterventional cholangitis and pancreatitis occurred in 16% of examinations; however, except from one case, all were mild or moderate and no procedure-associated mortality occurred. CONCLUSIONS: Digital SOVC-assisted biliary stone treatment is highly effective even in cases with difficult biliary stones and might be considered the new standard of care for these patients. Furthermore, mild up to moderate complications were intermittently observed which might document the complexity of our included cases.

Probing the acetylation code of histone H4.

Histone modifications play crucial roles in genome regulation with lysine acetylation being implicated in transcriptional control. Here we report a proteome-wide investigation of the acetylation-dependent protein-protein interactions of the N-terminal tail of histone H4. Quantitative peptide-based affinity MS experiments using the SILAC approach determined the interactomes of H4 tails monoacetylated at the four known acetylation sites K5, K8, K12, and K16, bis-acetylated at K5/K12, triple-acetylated at K8/12/16 and fully tetra-acetylated. A set of 29 proteins was found enriched on the fully acetylated H4 tail while specific binders of the mono and bis-acetylated tails were barely detectable. These observations are in good agreement with earlier reports indicating that the H4 acetylation state establishes its regulatory effects in a cumulative manner rather than via site-specific recruitment of regulatory proteins.

Improved two-dimensional reversed phase-reversed phase LC-MS/MS approach for identification of peptide-protein interactions.

Quantitative mass spectrometry (MS) in combination with affinity purification approaches allows for an unbiased study of protein-protein and peptide-protein interactions. In shotgun approaches that are based on proteolytic digestion of complex protein mixtures followed by two-dimensional liquid-phase chromatography, the separation effort prior to MS analysis is focused on tryptic peptides. Here we developed an improved offline 2-D liquid chromatography-MS/MS approach for the identification and quantification of binding proteins utilizing reversed-phase capillary columns with acidic acetonitrile-containing eluents in both chromatographic dimensions. A specific fractionation scheme was applied in order to obtain samples with evenly distributed peptides and to fully utilize the separation space in the second dimension nanoLC-MS/MS. We report peptide-protein interaction studies to identify phosphorylation-dependent binding partners of the T cell adapter protein ADAP. The results of the SILAC-based pull-down experiments show this approach is well suited for distinguishing phosphorylation-specific interactions from unspecific binding events. The data provide further evidence that phosphorylated Tyr 595 of ADAP may serve as a direct binding site for the SH2 domains of the T cell proteins SLP76 and NCK. From a technical point of view we provide a detailed protocol for an offline 2-D RP-RP LC-MS/MS method that offers a robust and time-saving alternative for quantitative interactome analysis.

Asociación del peso al nacer con adiposidad en niños escolares de distintas regiones de argentina / Association of birth weight with adiposity in school children from different regions of argentina

Introducción: diversos estudios han sugerido que el bajo y alto peso al nacer (PN) se asocian a obesidad (OB) y sobrepeso (SP) durante la infancia y la edad adulta. Objetivos: determinar la asociación entre PN y OB en escolares de 9 años de tres regiones de Argentina. Materiales y métodos: las medidas antropométricas y la presión arterial (PA) se tomaron en 1.131 escolares (505 masculinos) de 8,8±2,1 años de edad promedio, en tres regiones de Argentina durante el año 2019. Se interrogó, además, acerca del peso al nacer y el estilo de vida. Resultados: el 21,1% (239) de los niños presentaba SP (IMC>85 <95 percentilo según CDC) y el 21,8% (246) OB (IMC>95 percentilo). La prevalencia de PN bajo (<2.500 g) fue de fue de 6,2% (n=70) y de PN alto (>4.000 g) de 7,3% (n=82). El puntaje z-IMC de los niños de 9 años aumentaba significativamente con el aumento del PN: PN bajo (z-IMC=0,33), normal (z-IMC=0,72) y alto (z-IMC=1,12). En modelos de regresión logística múltiple se observó que el PN bajo se asoció inversamente a la OB (OR, 0.41 [IC del 95%: 0,19-0,92]), mientras que el PN alto se asoció directamente con la OB ajustado por edad y sexo (OR, 2.48 [95% IC 1,53-4,02]). Conclusiones: nuestros datos indican que el alto PN, pero no el bajo PN, se asocia con OB en niños en edad escolar de 9 años, mientras que el bajo PN está inversamente asociado con OB.

Introduction: several studies have suggested that low and high birth weight are associated with obesity (OB) and overweight (OW) during childhood and adulthood. Objectives: to determine the association between birth weight and OB in 9-year-old schoolchildren from three areas of Argentina. Materials and methods: anthropometric measurements and blood pressure (BP) were taken in 1.131 schoolchildren (505 males) of an average age of 8.8±2.1 years in three areas of Argentina during 2019. Mothers were asked about their children's birth weight and lifestyle. Results: 21.1% (239) of the children had OW (BMI>85 <95 percentile according to the CDC) and 21.8% (246) OB (BMI>95 percentile). The prevalence of low birth weight (<2.500 g) was 6.2% (n=70) and of high birth weight (>4.000 g) was 7.3% (n=82). The 9-year-old z-BMI score increased significantly with increasing birth weight: low birth weight (z-BMI=0.33), normal (z-BMI=0.72) and high (z-BMI=1.12). In multiple logistic regression models, it was found that low birth weight was inversely associated with OB (OR, 0.41 [95% CI: 0.19-0.92]), while high birth weight was directly associated with OB adjusted for age and sex (OR, 2.48 [95% CI 1.53-4.02]). Conclusions: our data indicate that high birth weight, but not low birth weight, is associated with OB in 9-year-old schoolchildren, while low birth weight is inversely associated with OB