An expression module of WIPF1-coexpressed genes identifies patients with favorable prognosis in three tumor types

Wiskott–Aldrich syndrome (WAS) predisposes patients to leukemia and lymphoma. WAS is caused by mutations in the protein WASP which impair its interaction with the WIPF1 protein. Here, we aim to identify a module of WIPF1-coexpressed genes and to assess its use as a prognostic signature for colorectal cancer, glioma, and breast cancer patients. Two public colorectal cancer microarray data sets were used for discovery and validation of the WIPF1 co-expression module. Based on expression of the WIPF1 signature, we classified more than 400 additional tumors with microarray data from our own experiments or from publicly available data sets according to their WIPF1 signature expression. This allowed us to separate patient populations for colorectal cancers, breast cancers, and gliomas for which clinical characteristics like survival times and times to relapse were analyzed. Groups of colorectal cancer, breast cancer, and glioma patients with low expression of the WIPF1 co-expression module generally had a favorable prognosis. In addition, the majority of WIPF1 signature genes are individually correlated with disease outcome in different studies. Literature gene network analysis revealed that among WIPF1 co-expressed genes known direct transcriptional targets of c-myc, ESR1 and p53 are enriched. The mean expression profile of WIPF1 signature genes is correlated with the profile of a proliferation signature. The WIPF1 signature is the first microarray-based prognostic expression signature primarily developed for colorectal cancer that is instrumental in other tumor types: low expression of the WIPF1 module is associated with better prognosis

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Inherited p40phox deficiency differs from classic chronic granulomatous disease

Biallelic loss-of-function (LOF) mutations of the NCF4 gene, encoding the p40phox subunit of the phagocyte NADPH oxidase, have been described in only 1 patient. We report on 24 p40phox-deficient patients from 12 additional families in 8 countries. These patients display 8 different in-frame or out-of-frame mutations of NCF4 that are homozygous in 11 of the families and compound heterozygous in another. When overexpressed in NB4 neutrophil-like cells and EBV-transformed B cells in vitro, the mutant alleles were found to be LOF, with the exception of the p.R58C and c.120_134del alleles, which were hypomorphic. Particle-induced NADPH oxidase activity was severely impaired in the patients' neutrophils, whereas PMA-induced dihydrorhodamine-1,2,3 (DHR) oxidation, which is widely used as a diagnostic test for chronic granulomatous disease (CGD), was normal or mildly impaired in the patients. Moreover, the NADPH oxidase activity of EBV-transformed B cells was also severely impaired, whereas that of mononuclear phagocytes was normal. Finally, the killing of Candida albicans and Aspergillus fumigatus hyphae by neutrophils was conserved in these patients, unlike in patients with CGD. The patients suffer from hyperinflammation and peripheral infections, but they do not have any of the invasive bacterial or fungal infections seen in CGD. Inherited p40phox deficiency underlies a distinctive condition, resembling a mild, atypical form of CGD.info:eu-repo/semantics/publishedVersio

Inherited p40^{phox} deficiency differs from classic chronic granulomatous disease

Biallelic loss-of-function (LOF) mutations of the NCF4 gene, encoding the p40^{phox} subunit of the phagocyte NADPH oxidase, have been described in only 1 patient. We report on 24 p40^{phox}-deficient patients from 12 additional families in 8 countries. These patients display 8 different in-frame or out-of-frame mutations of NCF4 that are homozygous in 11 of the families and compound heterozygous in another. When overexpressed in NB4 neutrophil-like cells and EBV-transformed B cells in vitro, the mutant alleles were found to be LOF, with the exception of the p.R58C and c.120_134del alleles, which were hypomorphic. Particle-induced NADPH oxidase activity was severely impaired in the patients’ neutrophils, whereas PMA-induced dihydrorhodamine-1,2,3 (DHR) oxidation, which is widely used as a diagnostic test for chronic granulomatous disease (CGD), was normal or mildly impaired in the patients. Moreover, the NADPH oxidase activity of EBV-transformed B cells was also severely impaired, whereas that of mononuclear phagocytes was normal. Finally, the killing of Candida albicans and Aspergillus fumigatus hyphae by neutrophils was conserved in these patients, unlike in patients with CGD. The patients suffer from hyperinflammation and peripheral infections, but they do not have any of the invasive bacterial or fungal infections seen in CGD. Inherited p40^{phox} deficiency underlies a distinctive condition, resembling a mild, atypical form of CGD

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Anales de la Academia de Medicina de Medellín, Año 1, No. 06. Abril. 1888. Primera época

Extracto del acta del 9 de julio de 1888. Pag.165-167 * Sres. Academicos. Pag.167-170 * Informe del Secretatrio. Pag. 170- 185 * Discurso del Gobernador del Departamento. Pag.185-186 * El Carbunclo. Pag.186-190 * Higiene de la Ciudad. El Polvo. Pag. 190-193 * Circular. Pag.19

Letras y Encajes

Letras y Encajes publica su primer número en 1926; esta revista fue fundada por mujeres de la clase dirigente de Medellín, muchas de ellas socias de la institución cultural Centro Femenino de Estudios (Sofía Ospina de Navarro, Teresa Santamaría de González, Ángela Villa de Toro y Alicia Merizalde de Echavarría), a lo largo del tiempo se consolidó como la revista femenina más importante del país, dirigida a mujeres de la clase alta y media, abordaba temas que giraban alrededor del hogar, la religión, la literatura y la moda de la época. La revista circuló mensualmente hasta 1959. Sus principales redactoras eran mujeres, pero contaba con la colaboración ocasional de algunos hombres y con traducciones de autoras y autores extranjeras

Potential cognitive endophenotypes in multigenerational families: segregating ADHD from a genetic isolate

Endophenotypes are neurobiological markers cosegregating and associated with illness. These biomarkers represent a promising strategy to dissect ADHD biological causes. This study was aimed at contrasting the genetics of neuropsychological tasks for intelligence, attention, memory, visual-motor skills, and executive function in children from multigenerational and extended pedigrees that cluster ADHD in a genetic isolate. In a sample of 288 children and adolescents, 194 (67.4%) ADHD affected and 94 (32.6%) unaffected, a battery of neuropsychological tests was utilized to assess the association between genetic transmission and the ADHD phenotype. We found significant differences between affected and unaffected children in the WISC block design, PIQ and FSIQ, continuous vigilance, and visual-motor skills, and these variables exhibited a significant heritability. Given the association between these neuropsychological variables and ADHD, and also the high genetic component underlying their transmission in the studied pedigrees, we suggest that these variables be considered as potential cognitive endophenotypes suitable as quantitative trait loci (QTLs) in future studies of linkage and association