Co-expression in tissue-specific gene networks links genes in cancer-susceptibility loci to known somatic driver genes.

BACKGROUND: The genetic background of cancer remains complex and challenging to integrate. Many somatic mutations within genes are known to cause and drive cancer, while genome-wide association studies (GWAS) of cancer have revealed many germline risk factors associated with cancer. However, the overlap between known somatic driver genes and positional candidate genes from GWAS loci is surprisingly small. We hypothesised that genes from multiple independent cancer GWAS loci should show tissue-specific co-regulation patterns that converge on cancer-specific driver genes. RESULTS: We studied recent well-powered GWAS of breast, prostate, colorectal and skin cancer by estimating co-expression between genes and subsequently prioritising genes that show significant co-expression with genes mapping within susceptibility loci from cancer GWAS. We observed that the prioritised genes were strongly enriched for cancer drivers defined by COSMIC, IntOGen and Dietlein et al. The enrichment of known cancer driver genes was most significant when using co-expression networks derived from non-cancer samples of the relevant tissue of origin. CONCLUSION: We show how genes within risk loci identified by cancer GWAS can be linked to known cancer driver genes through tissue-specific co-expression networks. This provides an important explanation for why seemingly unrelated sets of genes that harbour either germline risk factors or somatic mutations can eventually cause the same type of disease.

Impact of Single-Time-Point Estimates of 177Lu-PRRT Absorbed Doses on Patient Management: Validation of a Trained Multiple-Linear-Regression Model in 159 Patients and 477 Therapy Cycles.

Dosimetry after 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) enables estimation of radiation doses absorbed by normal organs and target lesions. This process is time-consuming and requires multiple posttreatment studies on several subsequent days. In a previous study, we described a newly developed multiple-linear-regression model to predict absorbed doses (ADs) from a single-time-point (STP) posttreatment study acquired 168 h after the first infusion and 24 h after the following ones, with similar results to the standard multiple-time-point (MTP) protocol. The present study aimed to validate this model in a large patient cohort and to assess whether STP dosimetry affects patient management decisions compared with our MTP protocol. Methods: Quantitative 177Lu-DOTATATE SPECT/CT post-PRRT data from 159 consecutive patients (172 therapies, 477 therapy cycles) were retrospectively analyzed. ADs obtained from an STP model were compared with those obtained using an MTP model. We evaluated the impact of the STP model on the decision on whether PRRT should be stopped because of an expected kidney AD exceeding the safety threshold. We hypothesized that patient management based on the STP model does not differ from that based on the MTP model in at least 90% of the cases. Results: There was no difference in management decisions between the MTP and STP models in 170 of 172 therapies (98.8%). A Fisher χ2 test for combined probabilities produced a composite P value of 0.0003. Mean cumulative AD relative differences between the STP and MTP models were 0.8% ± 8.0%, -7.7% ± 4.8%, 0.0% ± 11.4%, -2.8% ± 6.3%, and -2.1% ± 18.4% for kidneys, bone marrow, liver, spleen, and tumors, respectively (Pearson r = 0.99 for all), for patients who underwent 4 therapy cycles. Similar results were obtained with fewer therapy cycles. Conclusion: Estimated radiation ADs and patient management decisions were similar with the STP and MTP models. The STP model can simplify the dosimetry process while also reducing scanner and staff time and improving patient comfort.

Impact of Envenomation With Snake Venoms on Rabbit Carcass Decomposition and Differential Adult Dipteran Succession Patterns.

The current study investigates the postmortem successional patterns of necrophagous dipteran insects and the rabbit carcass decomposition rate upon envenomation with snake venom. In total, 15 rabbits, Oryctolagus cuniculus domesticus L. (Lagomorpha, Leporidae), were divided into 3 groups (5 rabbits each; n = 5); the first and second groups were injected with lethal doses of venoms from the Egyptian cobra, Naja haje L. (Squamata, Elapidae), and the horned viper, Cerastes cerastes L. (Squamata, viperidae), respectively. The third group (control) was injected with 0.85% physiological saline and euthanized with CO2. The carcass decomposition stages: fresh, bloating, decay, and dry were recorded and monitored. Data revealed that envenomation shortened the decomposition process by 3 d, 20% shorter than the control. The overall succession pattern of fly species revealed a lower abundance during the fresh stage, which peaked during the decay stage, and declined to the minimum number in the dry stage at the end of the 15-d experimental duration. A total of 2,488 individual flies, belonging to 21 species of 10 families, were collected from all experimental carcasses. The Calliphoridae, Muscidae, and Sarcophagidae were the most abundant and diverse families, whereas the other seven families were rare and least abundant. Although C. cerastes venom was significantly less lethal than N. haje, it showed a faster carcass decomposition process and a higher impact on fly abundance. These data showed that envenomation impacts insect succession and carcass decomposition, which should be taken into account when using insects in forensic investigations since envenomation with snake venoms is one of the leading causes of death worldwide.

Organic Solar Cells Parameters Extraction and Characterization Techniques.

Organic photovoltaic research is continuing in order to improve the efficiency and stability of the products. Organic devices have recently demonstrated excellent efficiency, bringing them closer to the market. Understanding the relationship between the microscopic parameters of the device and the conditions under which it is prepared and operated is essential for improving performance at the device level. This review paper emphasizes the importance of the parameter extraction stage for organic solar cell investigations by offering various device models and extraction methodologies. In order to link qualitative experimental measurements to quantitative microscopic device parameters with a minimum number of experimental setups, parameter extraction is a valuable step. The number of experimental setups directly impacts the pace and cost of development. Several experimental and material processing procedures, including the use of additives, annealing, and polymer chain engineering, are discussed in terms of their impact on the parameters of organic solar cells. Various analytical, numerical, hybrid, and optimization methods were introduced for parameter extraction based on single, multiple diodes and drift-diffusion models. Their validity for organic devices was tested by extracting the parameters of some available devices from the literature.

Simple model for estimation of absorbed dose by organs and tumors after PRRT from a single SPECT/CT study.

BACKGROUND: Following each cycle of peptide receptor radionuclide therapy (PRRT), absorbed doses by tumors and normal organs are typically calculated from three quantitative single-photon emission computed tomography (SPECT)/computed tomography (CT) studies acquired at t1 = 24 h, t2 = 96 h, t3 = 168 h after the first cycle of treatment and from a single study at t1 after the subsequent cycles. In the present study, we have assessed the feasibility of a single SPECT/CT study after each PRRT cycle using a trained multiple linear regression (MLR) model for absorbed dose calculation and have evaluated its impact on patient management. Quantitative [177Lu]-DOTA-TATE SPECT/CT data after PRRT of seventy-two consecutive metastatic neuroendocrine tumors patients were retrospectively evaluated. A set of 40 consecutive studies was used to train the MLR model. The two independent variables of the model included the time of imaging after administration of the treatment and the radiopharmaceutical activity concentration in a given  organ/tumor. The dependent variable was the dose absorbed by the organ/tumor obtained with the standard protocol. For bone marrow dosimetry, the independent variables included the time of imaging, and the blood and remainder of the body activity concentration. The model was evaluated in 32 consecutive patients. Absorbed doses were assessed for kidneys, bone marrow, liver, spleen and tumor sites. RESULTS: There was no difference in management decisions, whether PRRT can be safely continued or not because unsafe absorbed dose to risk organs between the standard and the MLR model-based protocol using a single SPECT/CT study performed at t3 = 168 h after the first cycle and at t1 = 24 h after the subsequent cycles. Cumulative absorbed doses were obtained with mean relative differences of - 0.5% ± 5.4%, 1.6% ± 15.1%, - 6.2% ± 7.3%, - 5.5% ± 5.8% and 2.9% ± 12.7% for kidneys, bone marrow, liver, spleen and tumors, respectively (Pearson's r correlation coefficient 0.99, 0.91, 0.99, 0.99 and 0.97, respectively). CONCLUSION: Dosimetry calculations using a MLR model with a single SPECT/CT study are in good agreement with the standard protocol, while avoiding the use of dosimetry software and enabling improved patient comfort and reduced scanner and staff time.

Donor cell microchimerism in kidney transplantation: Implications for graft function.

Given the uncertainty regarding the relationship between donor cells at microchimeric levels and its influence on graft function and clinical outcome, we explored the extent and importance of donor microchimerism in kidney transplantation. Twenty patients with chronic kidney disease who had received allografts from living donors were studied. We examined peripheral whole blood samples from the recipients one month after the transplant, applying mitochondrial DNA variant-specific polymerase chain reaction (PCR) to identify and quantify donor cells in relation to allograft function and survival during three years of follow-up. Higher quantities of donor-derived cell microchimerism in the peripheral blood correlated with better graft function in the early postoperative period at 1 month (R2  = .536, p = .001) and predicted improved graft function 1 year following the transplant (R2  = .430, p = .008). Furthermore, early post-transplant quantities of donor cell microchimerism were an important predictor of improved kidney function 3 years after transplantation (R2  = .397, p = .021). However, donor cell microchimerism failed to predict patient and graft survival after 3 years (odds ratio = 0.536, p = .860). Our findings suggest that donor cell microchimerism plays an immunoregulatory role in kidney transplantation and contributes to donor-specific immune hypo-responsiveness and graft acceptance.

Bacteriuria in pregnancy varies with the ambiance: a retrospective observational study at a tertiary hospital in Doha, Qatar.

Objectives To explore the influence of ambient temperature and humidity on significant bacteriuria (SB) and urinary bacterial isolates in pregnant women. Methods A retrospective observational study was conducted in the sole tertiary-care hospital in Doha, Qatar. A sample of 1588 pregnant women delivering between June 2012 and March 2013 was randomly selected. Meteorological variables including ambient average daily temperature and humidity were sourced from online meteorological data, and patient information such as demographic data, urine culture results and bacterial isolates were collected from patient files. The receptor operative curve (ROC) analysis was used to determine the cutoff for temperature and humidity. Statistical analyses of associations between SB and bacterial isolates with respect to the ambient temperature and humidity were performed using Pearson's correlation, the chi-square (χ2) test and the Kruskal-Wallis test. Results Of the 21.24% positive cultures, 11.25% had SB. SB showed a significant strong positive (r = +0.677, n = 17, P = 0.003) and moderate negative (r = -0.587, n = 17, P = 0.013) correlation with average monthly temperature and humidity, respectively, with doubling of rates noted with temperatures ≥35°C (11.3% vs. 3.6%; P < 0.0001) and humidity ≤50% (10.6% vs. 3.2%; P < 0.0001). Escherichia coli and Group B Streptococcus (GBS) were the most common isolates. Conclusion This is the first study in this region that demonstrates maternal risk with SB, with ambient temperatures of ≥35°C and humidity ≤50%. The effect of these variables on the growth of various urinary bacteria has also been shown.

Effect of Duration of Intensive Care Unit Stay on Outcomes of Adult Living Donor Liver Transplant Recipients.

BACKGROUND AND AIM: Acute kidney injury (AKI) is common in patients undergoing liver transplantation and is associated with reduced patient and graft survival. The aim is to assess the occurrence of AKI following living donor liver transplantation and to evaluate the associated risk factors and outcomes. SUBJECTS AND METHODS: Forty-nine Egyptian patients with hepatitis C virus who underwent living donor liver transplantation were divided into Group A (17 patients with AKI defined as increased creatinine > 50% of the initial pretransplant level) and Group B (non-AKI patients). Fluid balance, kidney function, preoperative and intraoperative risk factors, outcomes, and 1-year mortality were assessed. RESULTS: The mean age was 48 ± 7.51 and the majority of patients assessed were men (89.8%). The 17 patients with AKI had higher preoperative creatinine and higher Model for End-Stage Liver Disease scores (1.3 ± 0.16, 15.7 ± 5.07, respectively) than the non-AKI patients (1.1 ± .15, 13.7 ± 4.61, respectively), with P values of .04 and < .01, respectively. They also had significantly lower levels of albumin (2.98 ± .50). AKI patients had longer intensive care unit (ICU) stays (10 ± 3 d) compared to non-AKI patients (5 ± 2), with a P value of .03. A logistic multivariable regression test revealed that only a long ICU stay is a predictor of developing acute kidney injury among patients who have undergone living donor liver transplantation (odds ratio 1.23, 95% confidence interval 1.1-2.1, with a P value of .012). CONCLUSION: Many pre- and intra-operative factors are associated with AKI development; however, a long ICU stay is an independent potential factor for kidney infection.

ANTIMICROBIAL ACTIVITY FOR EXCRETION AND SECRETION OF THE GREENBOTTLE FLY LARVAE LUCILIA SERICATA (MEIGEN) (DIPTERA: CALLIPHORIDAE).

Sterile larval excretion/secretion (ES) exhibited antibacterial activity against some species of bacteria. They were shown to inhibit the growth of Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis Gram-negative bacteria Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae and Fungi Geotricum candidum and Aspergillus fumigatus thus exhibited limited inhibitory effect towards Gram-positive bacteria Streptococcus pyogenes and Staphylococcus epidermidis and Gram-negative Proteous vulgaris and Fungi Syncephalastrum racemosum, Candida albicans, that effect was slowed down when challenged with secretion on a solid media but no zone of complete inhibition was detectqd. Growth inhibiting activity was determined in liquid growth media using the Gram-positive, Gram-negative bacterial and fungal strains as indicator organisms.

Intraumbilical injection of three different uterotonics in the management of retained placenta.

AIM: The aim of this work was to compare the effect of intraumbilical injection of three different uterotonic solutions in the management of retained placenta. MATERIALS AND METHODS: This study was conducted in Ain-Shams University Maternity Hospital, Cairo, Egypt. A total of 78 women with retained placenta (>30 min after delivery of the fetus) were included in the study and subdivided into three groups. Each group was injected with a different type of uterotonic into the umbilical vein after clamping it using the Pipingas technique. Uterotonics used were either 20 IU oxytocin dissolved in 30 mL saline (n=26), ergometrine 0.2 mg dissolved in 30 mL saline (n=27) or misoprostol 800 µg dissolved in 30 mL saline (n=25). RESULTS: The overall success rate of spontaneous placental separation within 30 min after intraumbilical injection of uterotonics was 56/78 (71.79%). The success rate was higher with misoprostol when compared to oxytocin and ergometrine but the difference was not significant (20/25 [80%], 19/26 [73.08%], 17/27 [62.96%], respectively, P>0.05). The injection-to-separation interval was significantly shorter in the misoprostol group than in the oxytocin and ergometrine groups (7.0±2.2 min, 13.14±3.76 min, 22.5±4.37 min, respectively, P<0.001). CONCLUSION: Intraumbilical injection of uterotonics, namely oxytocin, ergometrine and dissolved misoprostol in saline, are closely effective in the management of retained placenta, with misoprostol being slightly more effective. This method may have a role in minimizing the need for manual removal of the placenta and its adverse sequelae.