Postoperative infections: Aetiology, incidence and risk factors among neurosurgical patients in Mthatha, South Africa

Background. Despite progress in hospital care, infections continue to represent one of the major complications among hospitalised patients.Objectives. To determine the aetiology and incidence of hospital-acquired infections and their associated risk factors following neurosurgical procedures.Methods. A retrospective study was conducted from October 2013 to September 2014. Data including demographics, hospitalisation period, type of operation and primary diagnosis were collected. Post-surgical infections were confirmed microbiologically. SPSS (Statistical Package for the Social Sciences) version 23 was used for statistical analysis.Results. Among a total of 1 688 patients who underwent neurosurgical operations, the incidence of post-surgical infections was 4.2% per year. Post-surgical infections were significantly associated with craniotomy (p<0.0001), prolonged stay in hospital (≥30 days) (p=0.008), and patient age ≥35 years (p=0.05). Staphylococcus aureus was the most frequently isolated pathogen (19.7%), followed by Klebsiella pneumoniae (12.7%). A total of 42.9% of S. aureus isolates were methicillin-resistant S. aureus (MRSA), but all these isolates were susceptible to vancomycin; 44.4% of K. pneumoniae isolates were extended-spectrum beta-lactamase (ESBL)-positive, but were susceptible to carbapenems, piperacillin-tazobactam and amikacin.Conclusions. Post-surgical infections remain an important problem in neurosurgery. Increased resistance to causative pathogens is a major concern.

Proteogenomic analysis of human colon cancer reveals new therapeutic opportunities

We performed the first proteogenomic study on a prospectively collected colon cancer cohort. Comparative proteomic and phosphoproteomic analysis of paired tumor and normal adjacent tissues produced a catalog of colon cancer-associated proteins and phosphosites, including known and putative new biomarkers, drug targets, and cancer/testis antigens. Proteogenomic integration not only prioritized genomically inferred targets, such as copy-number drivers and mutation-derived neoantigens, but also yielded novel findings. Phosphoproteomics data associated Rb phosphorylation with increased proliferation and decreased apoptosis in colon cancer, which explains why this classical tumor suppressor is amplified in colon tumors and suggests a rationale for targeting Rb phosphorylation in colon cancer. Proteomics identified an association between decreased CD8 T cell infiltration and increased glycolysis in microsatellite instability-high (MSI-H) tumors, suggesting glycolysis as a potential target to overcome the resistance of MSI-H tumors to immune checkpoint blockade. Proteogenomics presents new avenues for biological discoveries and therapeutic development

HDNetDB: A Molecular Interaction Database for Network-Oriented Investigations into Huntington’s Disease

Huntington's disease (HD) is a progressive and fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene. Although HD is monogenic, its molecular manifestation appears highly complex and involves multiple cellular processes. The recent application of high throughput platforms such as microarrays and mass-spectrometry has indicated multiple pathogenic routes. The massive data generated by these techniques together with the complexity of the pathogenesis, however, pose considerable challenges to researchers. Network-based methods can provide valuable tools to consolidate newly generated data with existing knowledge, and to decipher the interwoven molecular mechanisms underlying HD. To facilitate research on HD in a network-oriented manner, we have developed HDNetDB, a database that integrates molecular interactions with many HD-relevant datasets. It allows users to obtain, visualize and prioritize molecular interaction networks using HD-relevant gene expression, phenotypic and other types of data obtained from human samples or model organisms. We illustrated several HDNetDB functionalities through a case study and identified proteins that constitute potential cross-talk between HD and the unfolded protein response (UPR). HDNetDB is publicly accessible at http://hdnetdb.sysbiolab.eu.CHDI Foundation [A-2666]; Portuguese Fundacao para a Ciencia e a Tecnologia [SFRH/BPD/70718/2010, SFRH/BPD/96890/2013, IF/00881/2013, UID/BIM/04773/2013 - CBMR, UID/Multi/04326/2013 - CCMAR]info:eu-repo/semantics/publishedVersio

Haematological profile of adult sickle cell disease patients in North Maharashtra

Background: Sickle cell anaemia is a major genetic disease in India that presents major challenges to our health care systems. Aim and Objective: The aim of this study was to evaluate the haematological profile of Sickle Cell Disease (SCD) patients in the steady state from tribal population of North Maharashtra. Material & methods: Thirty six sickle cell disease patients in steady state, 43 sickle cell carriers and 43 normal healthy volunteers with age group18-40 years were recruited for the study. Subjects having history of vaso-occlussive crisis, blood transfusion and serious illness within last three months were excluded from the study. Results: We found low levels of haemoglobin 7.86 ± 1.93gm/dl, Red Blood Cell count 2.93 ± 0.73 milli/cmm, as well as the Packed Cell Volume 27.18 ± 5.35% in the male and female SCD patients when compared with the carriers and normal subjects. Mean Corpuscular Volume 93.91 ± 6.9 was found to be higher whereas Mean Corpuscular Haemoglobin Concentration 28.71 ± 2.19 values were less (P<0.05) in the patients than the carriers and controls. Mean Corpuscular Haemoglobin 26.91 ± 2.07 levels of the patients were not statistically significant when compared with carriers and normal subjects. Conclusion: Our results show, moderate to severe anemia and high foetal haemoglobin levels in the adult SCD patients. Sickle cell carriers and the normal control subjects showed mild to moderate anaemia. The occurrence of anaemia in these patients suggests that there is strong need to monitor these patients, to prevent triggering factors of vaso-occlussive crisis. The data so obtained would help in the management, prevention and control programme for SCD patients at the primary health care centers in India

A novel role of ADGRF1 (GPR110) in promoting cellular quiescence and chemoresistance in human epidermal growth factor receptor 2-positive breast cancer

While G protein-coupled receptors (GPCRs) are known to be excellent drug targets, the second largest family of adhesion-GPCRs is less explored for their role in health and disease. ADGRF1 (GPR110) is an adhesion-GPCR and has an important function in neurodevelopment and cancer. Despite serving as a poor predictor of survival, ADGRF1’s coupling to G proteins and downstream pathways remain unknown in cancer. We evaluated the effects of ADGRF1 overexpression on tumorigenesis and signaling pathways using two human epidermal growth factor receptor-2-positive (HER2+) breast cancer (BC) cell-line models. We also interrogated publicly available clinical datasets to determine the expression of ADGRF1 in various BC subtypes and its impact on BC-specific survival (BCSS) and overall survival (OS) in patients. ADGRF1 overexpression in HER2+ BC cells increased secondary mammosphere formation, soft agar colony formation, and % of Aldefluor-positive tumorigenic population in vitro and promoted tumor growth in vivo. ADGRF1 co-immunoprecipitated with both Gαs and Gαq proteins and increased cAMP and IP1 when overexpressed. However, inhibition of only the Gαs pathway by SQ22536 reversed the pro-tumorigenic effects of ADGRF1 overexpression. RNA-sequencing and RPPA analysis revealed inhibition of cell cycle pathways with ADGRF1 overexpression, suggesting cellular quiescence, as also evidenced by cell cycle arrest at the G0/1 phase and resistance to chemotherapy in HER2+ BC. ADGRF1 was significantly overexpressed in the HER2-enriched BC compared to luminal A and B subtypes and predicted worse BCSS and OS in these patients. Therefore, ADGRF1 represents a novel drug target in HER2+ BC, warranting discovery of novel ADGRF1 antagonists

NPY1R exerts inhibitory action on estradiol-stimulated growth and predicts endocrine sensitivity and better survival in ER-positive breast cancer

G Protein-Coupled Receptors (GPCRs) represent the largest superfamily of cell-surface proteins. However, the expression and function of majority of GPCRs remain unexplored in breast cancer (BC). We interrogated the expression and phosphorylation status of 398 non-sensory GPCRs using the landmark BC proteogenomics and phosphoproteomic dataset from The Cancer Genome Atlas. Neuropeptide Y Receptor Y1 (NPY1R) gene and protein expression were significantly higher in Luminal A tumors versus other BC subtypes. The trend of NPY1R gene, protein, and phosphosite (NPY1R-S368s) expression was decreasing in the order of Luminal A, Luminal B, Basal, and human epidermal growth factor receptor 2 (HER2) subtypes. NPY1R gene expression increased in response to estrogen and reduced with endocrine therapy in estrogen receptor-positive (ER+) BC cells and xenograft models. Conversely, NPY1R expression decreased in ER+ BC cells resistant to endocrine therapies (estrogen deprivation, tamoxifen, and fulvestrant) in vitro and in vivo. NPY treatment reduced estradiol-stimulated cell growth, which was reversed by NPY1R antagonist (BIBP-3226) in ER+ BC cells. Higher NPY1R gene expression predicted better relapse-free survival and overall survival in ER+ BC. Our study demonstrates that NPY1R mediates the inhibitory action of NPY on estradiol-stimulated growth of ER+ BC cells, and its expression serves as a biomarker to predict endocrine sensitivity and survival in ER+ BC patients

Human cytomegalovirus may promote tumour progression by upregulating arginase-2

10.18632/oncotarget.9722Oncotarget73047221-4723