Biofilms on glacial surfaces: hotspots for biological activity.

Glaciers are important constituents in the Earth's hydrological and carbon cycles, with predicted warming leading to increases in glacial melt and the transport of nutrients to adjacent and downstream aquatic ecosystems. Microbial activity on glacial surfaces has been linked to the biological darkening of cryoconite particles, affecting albedo and increased melt. This phenomenon, however, has only been demonstrated for alpine glaciers and the Greenland Ice Sheet, excluding Antarctica.

Recent treatment advances and novel therapies in pancreas cancer: a review.

Purpose: Over the last couple of years, we have witnessed the availability of a wide variety of different therapeutic agents and the identification of effective combinations of existing ones that have transformed the way we approach and treat pancreatic cancer. Proof of this are the recent validations that combinations of conventional chemotherapy drugs, the FOLFIRINOX regimen and gemcitabine plus nab-paclitaxel, significantly improves clinical outcomes in patients with metastatic disease. However, deeper and more sophisticated understanding of the biology of this cancer as well as the ability to develop better and perhaps more precise drugs predict that the landscape may be changing even more.

Is there a role for the quantification of RRM1 and ERCC1 expression in pancreatic ductal adenocarcinoma?

Background: RRM1 and ERCC1 overexpression has been extensively investigated as potential predictive markers of tumor sensitivity to conventional chemotherapy agents, most thoroughly in lung cancer. However, data in pancreatic cancer are scarce.

Methods: We investigated the mRNA and protein expression of ERCC1 and RRM1 by RT-PCR and immunohistochemistry (IHC) in formalin-fixed, paraffin-embedded pancreatic ductal carcinoma (PDA) tissues.

Guidelines for application of continuous subcutaneous insulin infusion (insulin pump) therapy in the perioperative period.

Case reports indicate that diabetes patients receiving outpatient insulin pump therapy have been allowed to continue treatment during surgical procedures. Although allowed during surgery, there is actually little information in the medical literature on how to manage patients receiving insulin pump therapy during a planned surgical procedure. A multidisciplinary work group reviewed current information regarding the use of insulin pumps in the perioperative period.

Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer.

Background: Preclinical data support further investigation of ascorbic acid in pancreatic cancer. There are currently insufficient safety data in human subjects, particularly when ascorbic acid is combined with chemotherapy.

Methods And Findings: 14 subjects with metastatic stage IV pancreatic cancer were recruited to receive an eight week cycle of intravenous ascorbic acid (three infusions per week), using a dose escalation design, along with standard treatment of gemcitabine and erlotinib.

The effects of ischemia with and without remote conditioning on hyperemia induced decline in carotid-radial pulse wave velocity.

Ischemic conditioning has long held promise for preventing ischemic-reperfusion (I-R) injury. Although a number of studies have evaluated the effects of brief repeated episodes of ischemia before a prolonged ischemic episode on the cardiovascular system using clinical endpoints, more sensitive techniques by which to measure its effects are lacking. Since endothelial function is sensitive to I-R injury, flow mediated dilation of the brachial artery has been proposed for this purpose, but has significant limitations.

Reversible posterior leukoencephalopathy syndrome associated with concurrent bevacizumab, gemcitabine, and oxaliplatin for cholangiocarcinoma.

Introduction: Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare disorder characterized by altered mental status, seizure, hypertension, and symmetrical white matter edema (leukoencephalopathy) typically in the posterior cerebral hemispheres on brain imaging. It is often linked to certain medication use, in particular, chemotherapeutic agents. Here, we present a case of chemotherapy-related RPLS and review the current literature on this topic.

Temporal and geographic patterns of hypoglycemia among hospitalized patients with diabetes mellitus.

Background: Hypoglycemia is often cited as a barrier to achieving inpatient glycemic targets. We sought to characterize hypoglycemic events in our institution by work-shift cycle and by specific treatment area.

Methods: Capillary (bedside) and blood (laboratory) glucose values of <70 mg/dl for patients with either a known diagnosis of diabetes or with evidence of hyperglycemia were abstracted from our laboratory database for hospitalizations between October 1, 2007, and February 3, 2008.

Understanding and improving management of inpatient diabetes mellitus: the Mayo Clinic Arizona experience.

We present an overview of strategies our institution has taken to understand the state of its inpatient diabetes management. We first describe how we utilized information systems to assess inpatient glycemic control and insulin management in noncritically ill patients and discuss our findings regarding mean bedside glucose levels, the prevalence and frequency hypoglycemic and hyperglycemic events, the patterns of insulin therapy, and evidence of inpatient clinical inertia. We also review the development of a survey to determine practitioner attitudes and beliefs about inpatient diabetes.

Inpatient to outpatient transfer of diabetes care: planing for an effective hospital discharge.

Objective: To review data on diabetes discharge planning, provide a definition of an effective diabetes discharge, and summarize one institution's diabetes discharge planning processes in a teaching hospital.

Methods: We performed a MEDLINE search of the English-language literature published between January 1998 and December 2007 for articles related to the inpatient to outpatient transition of diabetes care. Regulatory guidelines about discharge planning were reviewed.

The reliability of a single pulse oximetry reading as a screening test for congenital heart disease in otherwise asymptomatic newborn infants.

Routine pulse oximetry has been studied to detect children with otherwise undiagnosed congenital heart disease prior to nursery discharge. The reported sensitivities in asymptomatic patients have been less than expected and vary widely, bringing into question the reliability of the test. The purpose of this study was to assess whether routine pulse oximetry contributes to identifying patients with critical congenital heart disease and to determine the reliability of a single pulse oximeter reading in screening asymptomatic newborn infants.

Reliability of a single pulse oximetry reading as a screening test for congenital heart disease in otherwise asymptomatic newborn infants: the importance of human factors.

Background: The use of routine pulse oximetry to detect neonates with undiagnosed congenital heart disease before nursery discharge has been studied. The reported sensitivities with asymptomatic patients have been less than expected and vary widely, bringing into question the reliability of the test. This study aimed to assess whether routine pulse oximetry contributes to identifying patients with critical congenital heart disease, and to determine the reliability of a single pulse oximeter reading for screening asymptomatic newborn infants.

The mismatch DNA repair heterodimer, hMSH2/6, regulates BLM helicase.

The human MSH2/6 complex is essential for mismatch recognition during the repair of replication errors. Although mismatch repair components have been implicated in DNA homologous recombination repair, the exact function of hMSH2/6 in this pathway is unclear. Here, we show that the recombinant hMSH2/6 protein complex stimulated the ability of the Bloom's syndrome gene product, BLM, to process Holliday junctions in vitro, an activity that could also be regulated by p53.

Somatic mutation of hPMS2 as a possible cause of sporadic human colon cancer with microsatellite instability.

Inactivation of DNA-mismatch repair underlies the genesis of microsatellite unstable (MSI) colon cancers. hPMS2 is one of several genes encoding components of the DNA-mismatch repair complex, and germline hPMS2 mutations have been found in a few kindreds with hereditary nonpolyposis colorectal carcinoma (HNPCC), in whom hereditary MSI colon cancers develop. However, mice bearing null hPMS2 genes do not develop colon cancers and hPMS2 mutations in sporadic human colon cancers have not been described.

Repair of large insertion/deletion heterologies in human nuclear extracts is directed by a 5' single-strand break and is independent of the mismatch repair system.

The repair of 12-, 27-, 62-, and 216-nucleotide unpaired insertion/deletion heterologies has been demonstrated in nuclear extracts of human cells. When present in covalently closed circular heteroduplexes or heteroduplexes containing a single-strand break 3' to the heterology, such structures are subject to a low level repair reaction that occurs with little strand bias. However, the presence of a single-strand break 5' to the insertion/deletion heterology greatly increases the efficiency of rectification and directs repair to the incised DNA strand.

Isolation of MutSbeta from human cells and comparison of the mismatch repair specificities of MutSbeta and MutSalpha.

A human MSH2-human MSH3 (hMSH2.hMSH3) complex of approximately 1:1 stoichiometry (human MutSbeta (hMutSbeta)) has been demonstrated in several human tumor cell lines and purified to near homogeneity. In vitro, hMutSbeta supports the efficient repair of insertion/deletion (I/D) heterologies of 2-8 nucleotides, is weakly active on a single-nucleotide I/D mispair, and is not detectably active on the eight base-base mismatches.

Increased transversions in a novel mutator colon cancer cell line.

We describe a novel mutator phenotype in the Vaco411 colon cancer cell line which increases the spontaneous mutation rate 10-100-fold over background. This mutator results primarily in transversion base substitutions which are found infrequently in repair competent cells. Of the four possible types of transversions, only three were principally recovered.

A naturally occurring hPMS2 mutation can confer a dominant negative mutator phenotype.

Defects in mismatch repair (MMR) genes result in a mutator phenotype by inducing microsatellite instability (MI), a characteristic of hereditary nonpolyposis colorectal cancers (HNPCC) and a subset of sporadic colon tumors. Present models describing the mechanism by which germ line mutations in MMR genes predispose kindreds to HNPCC suggest a "two-hit" inactivation of both alleles of a particular MMR gene. Here we present experimental evidence that a nonsense mutation at codon 134 of the hPMS2 gene is sufficient to reduce MMR and induce MI in cells containing a wild-type hPMS2 allele.

Binding of human recombinant 125I-interferon gamma to receptors on human cells.

Recombinant human interferon gamma (rIFN-gamma) produced in Escherichia coli was labeled with 125I to study its binding to receptors of HeLa and lymphoblastoid cells. All the cell lines examined had receptors for rIFN-gamma, although the binding varied considerably among different cell lines. The binding of 125I-rIFN-gamma was competed up to 90% by the addition of unlabeled rIFN-gamma, although not by the addition of IFN-alpha or -beta.

Binding of unglycosylated and glycosylated human recombinant interferon-gamma to cellular receptors.

Recombinant human interferons (IFNs), either unglycosylated produced in E. coli (rIFN-gamma) or glycosylated produced in CHO cells (g-rIFN-gamma), were labeled with 125I to similar specific activities to study their interaction with cell-surface receptors. When analyzed by gel electrophoresis, rIFN-gamma run as a single polypeptide of Mr 15,000-17,000, whereas g-rIFN-gamma separated into three components of Mr 20,000, 22,000, and 43,000, which corresponded to the known size of the two monomeric and one dimeric forms of glycosylated natural IFN-gamma.

Training in large group therapy.

The widespread use of large group meetings as a treatment modality has exceeded the availability of staff trained in large group methods. The basic elements of an inservice training program are regular attendance by experienced senior staff who serve as role models, the serious and open use of review meetings following each large group meeting, and the establishment of group norms that facilitate functioning. A few crucial norms are identified and their importance is illustrated with examples from large group meetings.