Damaged DNA Binding Protein 2 Plays a Role in Breast Cancer Cell Growth

The Damaged DNA binding protein 2 (DDB2), is involved in nucleotide excision repair as well as in other biological processes in normal cells, including transcription and cell cycle regulation. Loss of DDB2 function may be related to tumor susceptibility. However, hypothesis of this study was that DDB2 could play a role in breast cancer cell growth, resulting in its well known interaction with the proliferative marker E2F1 in breast neoplasia. DDB2 gene was overexpressed in estrogen receptor (ER)-positive (MCF-7 and T47D), but not in ER-negative breast cancer (MDA-MB231 and SKBR3) or normal mammary epithelial cell lines. In addition, DDB2 expression was significantly (3.0-fold) higher in ER-positive than in ER-negative tumor samples (P = 0.0208) from 16 patients with breast carcinoma. Knockdown of DDB2 by small interfering RNA in MCF-7 cells caused a decrease in cancer cell growth and colony formation. Inversely, introduction of the DDB2 gene into MDA-MB231 cells stimulated growth and colony formation. Cell cycle distribution and 5 Bromodeoxyuridine incorporation by flow cytometry analysis showed that the growth-inhibiting effect of DDB2 knockdown was the consequence of a delayed G1/S transition and a slowed progression through the S phase of MCF-7 cells. These results were supported by a strong decrease in the expression of S phase markers (Proliferating Cell Nuclear Antigen, cyclin E and dihydrofolate reductase). These findings demonstrate for the first time that DDB2 can play a role as oncogene and may become a promising candidate as a predictive marker in breast cancer

WiseEye: next generation expandable and programmable camera trap platform for wildlife research

Funding: The work was supported by the RCUK Digital Economy programme to the dot.rural Digital Economy Hub; award reference: EP/G066051/1. The work of S. Newey and RJI was part funded by the Scottish Government's Rural and Environment Science and Analytical Services (RESAS). Details published as an Open Source Toolkit, PLOS Journals at: http://dx.doi.org/10.1371/journal.pone.0169758Peer reviewedPublisher PD

Combining Computational Fluid Dynamics and Agent-Based Modeling: A New Approach to Evacuation Planning

We introduce a novel hybrid of two fields—Computational Fluid Dynamics (CFD) and Agent-Based Modeling (ABM)—as a powerful new technique for urban evacuation planning. CFD is a predominant technique for modeling airborne transport of contaminants, while ABM is a powerful approach for modeling social dynamics in populations of adaptive individuals. The hybrid CFD-ABM method is capable of simulating how large, spatially-distributed populations might respond to a physically realistic contaminant plume. We demonstrate the overall feasibility of CFD-ABM evacuation design, using the case of a hypothetical aerosol release in Los Angeles to explore potential effectiveness of various policy regimes. We conclude by arguing that this new approach can be powerfully applied to arbitrary population centers, offering an unprecedented preparedness and catastrophic event response tool

Identification of New Agonists and Antagonists of the Insect Odorant Receptor Co-Receptor Subunit

BACKGROUND: Insects detect attractive and aversive chemicals using several families of chemosensory receptors, including the OR family of olfactory receptors, making these receptors appealing targets for the control of insects. Insect ORs are odorant-gated ion channels, comprised of at least one common subunit (the odorant receptor co-receptor subunit, Orco) and at least one variable odorant specificity subunit. Each of the many ORs of an insect species is activated or inhibited by an unique set of odorants that interact with the variable odorant specificity subunits, making the development of OR directed insect control agents complex and laborious. However, several N-,2-substituted triazolothioacetamide compounds (VUAA1, VU0450667 and VU0183254) were recently shown to act directly on the highly conserved Orco subunit, suggesting that broadly active compounds can be developed. We have explored the chemical space around the VUAA1 structure in order to identify new Orco ligands. PRINCIPAL FINDINGS: We screened ORs from several insect species, using heterologous expression in Xenopus oocytes and an electrophysiological assay, with a panel of 22 compounds structurally related to VUAA1. By varying the nitrogen position in the pyridine ring and altering the moieties decorating the phenyl ring, we identified two new agonists and a series of competitive antagonists. Screening smaller compounds, similar to portions of the VUAA1 structure, also yielded competitive antagonists. Importantly, we show that Orco antagonists inhibit odorant activation of ORs from several insect species. Detailed examination of one antagonist demonstrated inhibition to be through a non-competitive mechanism. CONCLUSIONS: A similar pattern of agonist and antagonist sensitivity displayed by Orco subunits from different species suggests a highly conserved binding site structure. The susceptibility to inhibition of odorant activation by Orco antagonism is conserved across disparate insect species, suggesing the ligand binding site on Orco as a promising target for the development of novel, broadly active insect repellants

Constitutive RB1 mutation in a child conceived by in vitro fertilization: implications for genetic counseling

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to identify mutations associated with bilateral retinoblastoma in a quadruplet conceived by in vitro fertilization, and to trace the parental origin of mutations in the four quadruplets and their father.</p> <p>Methods</p> <p>Mutational screening was carried out by sequencing. Genotyping was carried out for determining quadruplet zygosity.</p> <p>Results</p> <p>The proband was a carrier of a novel <it>RB1</it> constitutive mutation (g.2056C>G) which was not detected in her father or her unaffected sisters, and of two other mutations (g.39606 C>T and g.174351T>A) also present in two monozygotic sisters. The novel mutation probably occurred de novo while the others were of likely maternal origin. The novel mutation, affecting the Kozak consensus at the 5'UTR of <it>RB1</it> and g.174351T>A were likely associated to retinoblastoma in the proband.</p> <p>Conclusion</p> <p>Molecular diagnosis of retinoblastoma requires genotypic data of the family for determining hereditary transmission. In the case of children generated by IVF with oocytes from an anonymous donor which had been stored in a cell repository, this might not be successfully accomplished, making precise diagnosis impracticable for genetic counseling.</p

Colostomy closure: how to avoid complications

Purpose: Colostomy is an operation frequently performed in pediatric surgery. Despite its benefits, it can produce significant morbidity. In a previous publication we presented our experience with the errors and complications that occurred during cases of colostomy creation. We now have focused in the morbidity related to the colostomy closure. The technical details that might have contributed to the minimal morbidity we experienced are described. Methods: The medical records of 649 patients who underwent colostomy closure over a 28-year period were retrospectively reviewed looking for complications following these procedures. Our perioperative protocol for colostomy closure consisted in: clear fluids by mouth and repeated proximal stoma irrigations 24 h prior to the operation. Administration of IV antibiotics during anesthesia induction and continued for 48 h. Meticulous surgical technique that included: packing of the proximal stoma, plastic drape to immobilize the surgical field, careful hemostasis, emphasis in avoiding contamination, cleaning the edge of the stomas to allow a good 2-layer, end-to-end anastomosis with separated long-term absorbable sutures, generous irrigation of the peritoneal cavity and subsequent layers with saline solution, closure by layers to avoid dead space, and avoidance of hematomas. No drains and no nasogastric tubes were used. Oral fluids were started the day after surgery and patients were discharged 48-72 h after the operation. Results: The original diagnoses of the patients were: anorectal malformation (583), Hirschsprung\u27s disease (53), and others (13). 10 patients (1.5%) had complications: 6 had intestinal obstruction (5 due to small bowel adhesions, 1 had temporary delay of the function of the anastomosis due to a severe size discrepancy between proximal and distal stoma with a distal microcolon) and 4 incisional hernias. There were no anastomotic dehiscences or wound infection. There was no bleeding, no anastomotic stricture and no mortality. Conclusion: Based on this experience we believe that colostomy closure can be performed with minimal morbidity provided a meticulous technique is observed. © 2010 The Author(s)

Neuronal circuitry for pain processing in the dorsal horn

Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region

Factors associated with return of spontaneous circulation after out-of-hospital cardiac arrest in Poland : a one-year retrospective study

Background: Out-of-hospital cardiac arrest (OHCA) is a common reason for calls for intervention by emergency medical teams (EMTs) in Poland. Regardless of the mechanism, OHCA is a state in which the chance of survival is dependent on rapid action from bystanders and responding health professionals in emergency medical services (EMS). We aimed to identify factors associated with return of spontaneous circulation (ROSC). Methods: The medical records of 2137 EMS responses to OHCA in the city of Wroclaw, Poland between July 2017 and June 2018 were analyzed. Results: The OHCA incidence rate for the year studied was 102 cases per 100,000 inhabitants. EMS were called to 2317 OHCA events of which 1167 (50.4%) did not have resuscitation attempted on EMS arrival. The difference between the number of successful and failed cardiopulmonary resuscitations (CPRs) was statistically significant (p < 0.001). Of 1150 patients in whom resuscitation was attempted, ROSC was achieved in 250 (27.8%). Rate of ROSC was significantly higher when CPR was initiated by bystanders (p < 0.001). Patients presenting with asystole or pulseless electrical activity (PEA) had a higher risk of CPR failure (86%) than those with ventricular fibrillation/ventricular tachycardia (VF/VT). Patients with VF/VT had a higher chance of ROSC (OR 2.68, 1.86–3.85) than those with asystole (p < 0.001). The chance of ROSC was 1.78 times higher when the event occurred in a public place (p < 0.001). Conclusions: The factors associated with ROSC were occurrence in a public place, CPR initiation by witnesses, and presence of a shockable rhythm. Gender, age, and the type of EMT did not influence ROSC. Low bystander CPR rates reinforce the need for further efforts to train the public in CPR

Influence of Comorbidities on Therapeutic Progression of Diabetes Treatment in Australian Veterans: A Cohort Study

BACKGROUND: This study assessed whether the number of comorbid conditions unrelated to diabetes was associated with a delay in therapeutic progression of diabetes treatment in Australian veterans. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort study was undertaken using data from the Australian Department of Veterans' Affairs (DVA) claims database between July 2000 and June 2008. The study included new users of metformin or sulfonylurea medicines. The outcome was the time to addition or switch to another antidiabetic treatment. The total number of comorbid conditions unrelated to diabetes was identified using the pharmaceutical-based comorbidity index, Rx-Risk-V. Competing risk regression analyses were conducted, with adjustments for a number of covariates that included age, gender, residential status, use of endocrinology service, number of hospitalisation episodes and adherence to diabetes medicines. Overall, 20134 veterans were included in the study. At one year, 23.5% of patients with diabetes had a second medicine added or had switched to another medicine, with 41.4% progressing by 4 years. The number of unrelated comorbidities was significantly associated with the time to addition of an antidiabetic medicine or switch to insulin (subhazard ratio [SHR] 0.87 [95% CI 0.84–0.91], P<0.001). Depression, cancer, chronic obstructive pulmonary disease, dementia, and Parkinson's disease were individually associated with a decreased likelihood of therapeutic progression. Age, residential status, number of hospitalisations and adherence to anti-diabetic medicines delayed therapeutic progression. CONCLUSIONS / SIGNIFICANCE: Increasing numbers of unrelated conditions decreased the likelihood of therapeutic progression in veterans with diabetes. These results have implications for the development of quality measures, clinical guidelines and the construction of models of care for management of diabetes in elderly people with comorbidities.Agnes I. Vitry, Elizabeth E. Roughead, Adrian K. Preiss, Philip Ryan, Emmae N. Ramsay, Andrew L. Gilbert, Gillian E. Caughey, Sepehr Shakib, Adrian Esterman, Ying Zhang and Robyn A. McDermot