Increased Levels of Genomic Instability and Mutations in Homologous Recombination Genes in Locally Advanced Rectal Carcinomas

Pre-operative 5-fluoracil-based chemoradiotherapy (nCRT) is the standard treatment for patients with locally advanced rectal cancer (LARC). Patients with pathological complete response (pCR–0% of tumor cells in the surgical specimen after nCRT) have better overall survival and lower risk of recurrence in comparison with incomplete responders (pIR). Predictive biomarkers to be used for new therapeutic strategies and capable of stratifying patients to avoid overtreatment are needed. We evaluated the genomic profiles of 33 pre-treatment LARC biopsies using SNP array and targeted-next generation sequencing (tNGS). Based on the large number of identified genomic alterations, we calculated the genomic instability index (GII) and three homologous recombination deficiency (HRD) scores, which have been reported as impaired DNA repair markers. We observed high GII in our LARC cases, which was confirmed in 165 rectal cancer cases from TCGA. Patients with pCR presented higher GII compared with pIR. Moreover, a negative correlation between GII and the fraction of tumor cells remaining after surgery was observed (ρ = –0.382, P = 0.02). High HRD scores were detected in 61% of LARC, of which 70% were incomplete responders. Using tNGS (105 cancer-related genes, 13 involved in HR and 5 in mismatch repair pathways), we identified 23% of cases with mutations in HR genes, mostly in pIR cases (86% of mutated cases). In agreement, the analysis of the TCGA dataset (N = 145) revealed 21% of tumors with mutations in HR genes. The HRD scores were shown to be predictive of better response to PARP-inhibitors and platinum-based chemotherapy in breast and ovarian cancer. Our results suggest that the same strategy could be applied in a set of LARC patients with HRD. In conclusion, we identified high genomic instability in LARC, which was related to alterations in the HR pathway, especially in pIR. These findings suggest that patients with impaired HRD would clinically benefit from PARP-inhibitors and platinum-based therapy

Factura, 1916 jul. 31, Madrid, de R. Catin Manufacture générale de Caouchouc al Sr. D. Moisés Martínez

Factura impresa en azul en ambas caras sin cumplimentar el reverso, numerada "341" y manuscrita en tinta negra en la aparece impresa la palabra "EXTRACTO"Alcance y contenido: Comunicación al Sr. Moisés Martínez de Zaragoza del extracto de su cuenta correspondiente al mes de la fecha que presenta un saldo a favor de la empresa de 295,25 pesetas. Para el reembolso se indica que se haga un giro de igual importe por conducto de D. Roberto Ripollés. Se indican fechas en la factura de operaciones diferentes que corresponden al 3 y 6 de julioEn la parte superior aparece impreso el nombre: "Manufacture générale de Caouchouc". En el lado izquierdo superior. Datos de dirección, teléfono y telégrafo: "Despacho y Fábrica / Zurbano, 64 Moderno / Teléfono 520 / Dirección telegráfica PARCAT, MADRID"Aparece indicada la persona destinataria y la localidad: "Sr. D. Moisés Martínez de Zaragoza"Firma rubricada de R. Catin en la que aparece un sello en tinta azul del mismo con el nombre de la empresaMembrete en azul sin ornamento, formado por el nombre. La dirección y la publicidad figuran en el lado derecho con notas explicativas de funcionamiento. Se presentan en líneas diferentes y tipografía variada según el resalte de la informaciónPapel en color crem

Analisa Kandungan Hara Kompos Limbah Daun Teh.

Limbah daun teh yang merupakan sisa hasil pengolahan dan dianggap sudah tidak dapat digunakan lagi pada umumnya akan dibuang. Namun limbah tersebut sebenarnya masih dapat diolah menjadi pupuk organik yang bermanfaat bagi tanaman. Penelitian pengolahan limbah kompos daun teh menjadi pupuk organik ini dilaksanakan di Laboratorium Teknologi Benih Universitas Methodist pada bulan Desember 2017-Januari 2018 dengan tujuan untuk membandingkan pengaruh dua jenis bioaktivator terhadap rasio C/N dan Ni, Na, Co, Mo, Mn tersedia pada kompos limbah daun teh. Dalam penelitian ini digunakan metode Uji T dua sampel dengan 1 taraf yaitu Bioaktivator Biotriba (B1) = 15 kg limbah daun teh + 15 ml biotriba/1 liter air dan Bioaktivator Primadec (P1) = 15 kg limbah daun teh + 150 ml larutan primadec diulang sebanyak = 3 kali. Parameter yang diamati, kandungan Ni (Nikel), kandungan Na (Natrium), kandungan Mn (Mangan), kandungan Mo (Molibdenum), kandungan Co (Cobalt), kandungan Karbon (C-Organik), Kandungan N (N-Total). Hasil dari pengamatan parameter pada penelitian ini menunjukkan bahwa kedua jenis bioaktivator yaitu bioaktivator biotriba dan bioaktivator primadec menunjukkan perubahan nilai unsure hara yang dikandung selama pengomposan

Aminoglycoside exposure and renal function before lung transplantation in adult cystic fibrosis patients

Background: Patients with cystic fibrosis (CF) are at risk of kidney injury even before undergoing lung transplantation, because of prolonged exposure to aminoglycosides (AGs), chronic dehydration and complications of diabetes mellitus. The usual equations estimating the glomerular filtration rate (GFR), such as Cockcroft-Gault and Modification of Diet in Renal Disease, are not adapted to the CF population due to patients' low body weight and reduced muscle mass. The aim of this study was to precisely measure GFR in adult CF patients and to see whether repeated AG treatment would impair renal function before lung transplantation. Methods: Inulin or iohexol clearances were performed in 25 adult CF patients when they entered the lung transplant waiting list. No patient was treated with AGs at the time of GFR measurement. Body mass index (BMI), history of diabetes mellitus and blood pressure were recorded. Exposure to intravenous (IV) AGs within 5 years prior to the GFR measurement was obtained from the patient's medical files. Urine samples were collected to check for albuminuria and proteinuria. Results: The population was predominantly female (67%). The mean age was 32 years, the mean BMI was 19 kg/m2 and 28% had CF-related diabetes. Median exposure to IV AG within 5 years before GFR measurement was 155 days with a mean dosage of 7.7mg/kg/day. The mean measured GFR was 106 mL/min/1.73 m2 and the mean estimated GFR according to the Chronic Kidney Disease Epidemiology Collaboration formula was 124 mL/min/1.73 m2. Conclusion: Despite prolonged exposure to high-dose IV AG, no decline in GFR was observed in these patients

Quantitative histomorphometric analysis of halved iliac crest bone biopsies yield comparable ROD diagnosis as full 7.5mm wide samples

BACKGROUND AND OBJECTIVES: Histomorphometric analysis of a transiliac bone biopsy is the gold standard for the diagnosis of renal osteodystrophy (ROD). This procedure is costly, invasive and usually performed with a trephine with an internal diameter of 7.5 mm. Our objective was to evaluate the accuracy of ROD diagnosis on halved histological bone sections to determine if they are comparable to the standard 7.5 mm samples. DESIGN: We included 68 bone biopsies performed in CKD patients for diagnostic purposes with a 7.5 mm diameter trephine. Quantitative histomorphometric analysis of the whole bone samples was performed including assessment of bone mineralization, turnover and volume. Each histological section (representing the whole 7.5 mm diameter biopsy) was then divided lengthwise in two hemisections (representing the 3.5 mm diameter biopsy). Histomorphometric analysis was repeated this time on the two hemibiopsies for each sample, blinded from initial results. Diagnoses were classified as osteitis fibrosa, adynamic bone disease, mixed uremic bone disease, osteomalacia or other. Correlations between the whole sample and the hemibiopsies for each parameter were studied. Concordance between the various bone parameters and final ROD diagnosis obtained from the whole section versus the two hemi sections was evaluated. RESULTS: Highly significant correlations were found between parameters measured on the whole section and the corresponding hemisections, with r coefficient of 0.98 for osteoid surface and thickness and bone formation rate, 0.97 for osteoclast surface, and 0.96 for bone volume (p \textless 0.001). Final diagnosis was in full accordance between the whole biopsy and the two corresponding hemi-biopsies in 91% of cases. CONCLUSIONS: Accurate diagnosis of ROD type was obtained by evaluation of bone surface areas of 3 mm diameter. These data suggest that small invasive bone biopsies might provide accurate ROD diagnostics while decreasing both invasiveness and cost of the procedure