Visualizing electron storage capacity distribution in biochar through silver tagging.

Electron storage capacity (ESC) is the capacity of a black carbon to store and reversibly donate and accept electrons in redox processes. Electrochemical and chemical analyses have shown the ESC of black carbon (e.g., plant-based biochars) was on the order of a few mmol/g. However, it remains unknown where ESC is located. The spatial distribution of ESC is important because it controls the bioaccessibility of ESC and the rates of biochar redox reactions. Here we used silver to tag the ESC of a wood-derived biochar. Ag+ was allowed to diffuse into the pores of reduced biochar at a constant pH. Up to 2.49 mmol Ag+/g biochar (corresponding to 62% of its ESC) was reduced to Ago nanoparticles (nAg), which served as an ESC marker and was visualized by electron microscopy. Abundant and dense nAg were observed on the biochar surface. In addition, microtomed samples showed ubiquitous and well-dispersed nAg in the interior of biochar, which explains pore diffusion-limited redox reactions and the partial bioaccessibility of its ESC. In addition to probing ESC distribution in black carbon, this method represents a new, ESC-based approach to incorporate large quantities of Ag and other redox-active elements into carbon media for potential environmental applications.

Identification and Prevention of Secondary Heart Failure: A Case Study.

Heart failure, a complex clinical syndrome affecting millions of Americans, is associated with high morbidity and mortality and a significant financial burden on the health care system. Recent health care reform efforts have focused on reducing 30-day heart failure hospital readmissions, increasing the cost-effectiveness of care provided to heart failure patients, and improving health outcomes for these patients. This case report describes an acutely ill patient with multiple comorbidities who was not initially admitted for heart failure but who developed acute decompensated heart failure during his hospital stay. The purpose of this in-depth analysis is to discuss the role of bedside nurses and advanced practice nurses in managing heart failure, describe the challenges of identifying secondary heart failure in patients with complex conditions, and suggest methods of improving health-related outcomes to prevent hospital readmissions.

Deleterious Germline Mutations in Patients With Apparently Sporadic Pancreatic Adenocarcinoma.

Purpose Deleterious germline mutations contribute to pancreatic cancer susceptibility and are well documented in families in which multiple members have had pancreatic cancer. Methods To define the prevalence of these germline mutations in patients with apparently sporadic pancreatic cancer, we sequenced 32 genes, including known pancreatic cancer susceptibility genes, in DNA prepared from normal tissue obtained from 854 patients with pancreatic ductal adenocarcinoma, 288 patients with other pancreatic and periampullary neoplasms, and 51 patients with non-neoplastic diseases who underwent pancreatic resection at Johns Hopkins Hospital between 2000 and 2015. Results Thirty-three (3.9%; 95% CI, 3.0% to 5.8%) of 854 patients with pancreatic cancer had a deleterious germline mutation, 31 (3.5%) of which affected known familial pancreatic cancer susceptibility genes: BRCA2 (12 patients), ATM (10 patients), BRCA1 (3 patients), PALB2 (2 patients), MLH1 (2 patients), CDKN2A (1 patient), and TP53 (1 patient). Patients with these germline mutations were younger than those without (mean ± SD, 60.8 ± 10.6 v 65.1 ± 10.5 years; P = .03). Deleterious germline mutations were also found in BUB1B (1) and BUB3 (1). Only three of these 33 patients had reported a family history of pancreatic cancer, and most did not have a cancer family history to suggest an inherited cancer syndrome. Five (1.7%) of 288 patients with other periampullary neoplasms also had a deleterious germline mutation. Conclusion Germline mutations in pancreatic cancer susceptibility genes are commonly identified in patients with pancreatic cancer without a significant family history of cancer. These deleterious pancreatic cancer susceptibility gene mutations, some of which are therapeutically targetable, will be missed if current family history guidelines are the main criteria used to determine the appropriateness of gene testing.

A novel approach for selecting combination clinical markers of pathology applied to a large retrospective cohort of surgically resected pancreatic cysts.

OBJECTIVE: Our objective was to develop an approach for selecting combinatorial markers of pathology from diverse clinical data types. We demonstrate this approach on the problem of pancreatic cyst classification. MATERIALS AND METHODS: We analyzed 1026 patients with surgically resected pancreatic cysts, comprising 584 intraductal papillary mucinous neoplasms, 332 serous cystadenomas, 78 mucinous cystic neoplasms, and 42 solid-pseudopapillary neoplasms. To derive optimal markers for cyst classification from the preoperative clinical and radiological data, we developed a statistical approach for combining any number of categorical, dichotomous, or continuous-valued clinical parameters into individual predictors of pathology. The approach is unbiased and statistically rigorous. Millions of feature combinations were tested using 10-fold cross-validation, and the most informative features were validated in an independent cohort of 130 patients with surgically resected pancreatic cysts. RESULTS: We identified combinatorial clinical markers that classified serous cystadenomas with 95% sensitivity and 83% specificity; solid-pseudopapillary neoplasms with 89% sensitivity and 86% specificity; mucinous cystic neoplasms with 91% sensitivity and 83% specificity; and intraductal papillary mucinous neoplasms with 94% sensitivity and 90% specificity. No individual features were as accurate as the combination markers. We further validated these combinatorial markers on an independent cohort of 130 pancreatic cysts, and achieved high and well-balanced accuracies. Overall sensitivity and specificity for identifying patients requiring surgical resection was 84% and 81%, respectively. CONCLUSIONS: Our approach identified combinatorial markers for pancreatic cyst classification that had improved performance relative to the individual features they comprise. In principle, this approach can be applied to any clinical dataset comprising dichotomous, categorical, and continuous-valued parameters.

Digital next-generation sequencing identifies low-abundance mutations in pancreatic juice samples collected from the duodenum of patients with pancreatic cancer and intraductal papillary mucinous neoplasms.

OBJECTIVE: Secretin-stimulated pancreatic juice contains DNA shed from cells lining the pancreatic ducts. Genetic analysis of this fluid may form a test to detect pancreatic ductal neoplasia. DESIGN: We employed digital next-generation sequencing ('digital NGS') to detect low-abundance mutations in secretin-stimulated juice samples collected from the duodenum of subjects enrolled in Cancer of the Pancreas Screening studies at Johns Hopkins Hospital. For each juice sample, digital NGS necessitated 96 NGS reactions sequencing nine genes. The study population included 115 subjects (53 discovery, 62 validation) (1) with pancreatic ductal adenocarcinoma (PDAC), (2) intraductal papillary mucinous neoplasm (IPMN), (3) controls with non-suspicious pancreata. RESULTS: Cases with PDAC and IPMN were more likely to have mutant DNA detected in pancreatic juice than controls (both p<0.0001); mutant DNA concentrations were higher in patients with PDAC than IPMN (p=0.003) or controls (p<0.001). TP53 and/or SMAD4 mutations were commonly detected in juice samples from patients with PDAC and were not detected in controls (p<0.0001); mutant TP53/SMAD4 concentrations could distinguish PDAC from IPMN cases with 32.4% sensitivity, 100% specificity (area under the curve, AUC 0.73, p=0.0002) and controls (AUC 0.82, p<0.0001). Two of four patients who developed pancreatic cancer despite close surveillance had SMAD4/TP53 mutations from their cancer detected in juice samples collected over 1 year prior to their pancreatic cancer diagnosis when no suspicious pancreatic lesions were detected by imaging. CONCLUSIONS: The detection in pancreatic juice of mutations important for the progression of low-grade dysplasia to high-grade dysplasia and invasive pancreatic cancer may improve the management of patients undergoing pancreatic screening and surveillance.

Obstructive Sleep Apnea and Pathological Characteristics of Resected Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Prospective studies have identified obstructive sleep apnea (OSA) as a risk factor for increased overall cancer incidence and mortality. The potential role of OSA in the risk or progression of specific cancers is not well known. We hypothesized that pathological differences in pancreatic cancers from OSA cases compared to non-OSA cases would implicate OSA in pancreatic cancer progression. METHODS: We reviewed the medical records of 1031 patients who underwent surgical resection without neoadjuvant therapy for pancreatic ductal adenocarcinoma (PDAC) at Johns Hopkins Hospital between 2003 and 2014 and compared the TNM classification of their cancer and their overall survival by patient OSA status. RESULTS: OSA cases were significantly more likely than non-OSA cases to have lymph node-negative tumors (37.7% vs. 21.8%, p = 0.004). Differences in the prevalence of nodal involvement of OSA vs. non-OSA cases were not associated with differences in other pathological characteristics such as tumor size, tumor location, resection margin status, vascular or perineural invasion, or other comorbidities more common to OSA cases (BMI, smoking, diabetes). A logistic regression model found that a diagnosis of OSA was an independent predictor of lymph node status (hazard ratio, 0.051, p = 0.038). Patients with OSA had similar overall survival compared to those without OSA (HR, 0.89, (0.65-1.24), p = 0.41). CONCLUSION: The observed pathological differences between OSA-associated and non-OSA-associated pancreatic cancers supports the hypothesis that OSA can influence the pathologic features of pancreatic ductal adenocarcinoma.

Hereditary Hemorrhagic Telangiectasia: A Primer for Critical Care Nurses.

Hereditary hemorrhagic telangiectasia is a rare, autosomal dominant genetic disease that causes abnormal growth of blood vessels and, subsequently, life-threatening arteriovenous malformations in vital organs. Epistaxis may be one of the initial clues that a patient has more serious, generalized arteriovenous malformations. Recommended treatment involves careful evaluation to determine the severity and risk of spontaneous rupture of the malformations and the management of various signs and symptoms. The disease remains undiagnosed in many patients, and health care providers may miss the diagnosis until catastrophic events happen in multiple family members. Prompt recognition of hereditary hemorrhagic telangiectasia and early intervention can halt the dangerous course of the disease. Critical care nurses can assist with early diagnosis within families with this genetic disease, thus preventing early death and disability.

Von Hippel-Lindau: Current Evidence in Diagnosis, Treatment, and Nursing Implications.

BACKGROUND: Von Hippel-Lindau (VHL) is a rare autosomal dominant hereditary disorder that predisposes individuals to benign and malignant tumors in the brain, eyes, kidneys, pancreas, genital tract, or other body parts. The VHL gene, which is located on the short arm of chromosome 3, prevents cells from dividing too rapidly. Mutations in the VHL gene result in uncontrollable cell growth and tumor formation. OBJECTIVES: The purpose of this article is to summarize the current research literature describing diagnosis, treatment, and nursing implications of VHL. METHODS: Three electronic databases, relevant journals, and relevant websites were searched. FINDINGS: The majority of patients affected with VHL have an affected parent, but a small percentage develop VHL from a new mutation that takes place in a single egg or sperm during conception or from a post-conception mutation. Genetic testing, either through sequence analysis, Southern blot analysis, or quantitative polymerase chain reaction, is considered standard in evaluating patients suspected of having VHL. A diagnosis of VHL can be made by identifying one VHL tumor for a patient who has a confirmed family history of VHL. The presence of at least two tumors is required to make a diagnosis of VHL in a patient without a positive family history. The nursing role includes providing resources on VHL genetic counseling, genetic testing, and palliative care.

Percutaneous closure of the left atrial appendage for stroke prevention in atrial fibrillation: an alternative to lifelong anticoagulation?

Atrial fibrillation is an important risk factor for thromboembolic stroke and it significantly increases the risk of stroke. The left atrial appendage (LAA) is the most common site of thrombus formation in nonvalvular atrial fibrillation, and the recent applications of percutaneous LAA closure devices offer a promising alternative for patients who are unable to tolerate lifelong anticoagulation. Critical care nurses who understand the procedures and are familiar with the various devices used for LAA closure will be well prepared to provide optimum care and appropriate education for these patients.

Understanding Insulin Pump Therapy.

It is estimated that 375,000 Americans are utilizing insulin pump therapy to manage their diabetes. This article will educate community health care nurses regarding use of the insulin pump, and how to operate special settings for more effective glycemic control. Complications of pump therapy, as well as hyperglycemia, are not always avoidable; however, interventions are in place to prevent and treat complications. Furthermore, important assessment questions are employed to assist community health nurses in evaluating the patient knowledge base and management skills of their disease process in hyperglycemic episodes and emergency situations.

Neuropathic Pain Management: A Reference for the Clinical Nurse.

The International Association for the Study of Pain neuropathic pain guidelines are presented. Nursing considerations, including neuropathic pain assessment and medication efficacy, are reported to explain medications' primary mechanisms of action and provide a nursing reference for patient education.

KRAS and guanine nucleotide-binding protein mutations in pancreatic juice collected from the duodenum of patients at high risk for neoplasia undergoing endoscopic ultrasound.

BACKGROUND & AIMS: Pancreatic imaging can identify neoplastic cysts but not microscopic neoplasms. Mutation analysis of pancreatic fluid after secretin stimulation might identify microscopic neoplasias in the pancreatic duct system. We determined the prevalence of mutations in KRAS and guanine nucleotide-binding protein α-stimulating genes in pancreatic juice from subjects undergoing endoscopic ultrasound for suspected pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasms, or pancreatic adenocarcinoma. METHODS: Secretin-stimulated juice samples were collected from the duodenum of 272 subjects enrolled in Cancer of the Pancreas Screening studies; 194 subjects were screened because of a family history of, or genetic predisposition to, pancreatic cancer, and 78 subjects were evaluated for pancreatic cancer (n = 30) or other disorders (controls: pancreatic cysts, pancreatitis, or normal pancreata, n = 48). Mutations were detected by digital high-resolution melt-curve analysis and pyrosequencing. The number of replicates containing a mutation determined the mutation score. RESULTS: KRAS mutations were detected in pancreatic juice from larger percentages of subjects with pancreatic cancer (73%) or undergoing cancer screening (50%) than controls (19%) (P = .0005). A greater proportion of patients with pancreatic cancer had at least 1 KRAS mutation detected 3 or more times (47%) than screened subjects (21%) or controls (6%, P = .002). Among screened subjects, mutations in KRAS (but not guanine nucleotide-binding protein α-stimulating) were found in similar percentages of patients with or without pancreatic cysts. However, a greater proportion of patients older than age 50 years had KRAS mutations (54.6%) than younger patients (36.3%) (P = .032); the older subjects also had more mutations in KRAS (P = .02). CONCLUSIONS: Mutations in KRAS are detected in pancreatic juice from the duodenum of 73% of patients with pancreatic cancer, and 50% of asymptomatic individuals with a high risk for pancreatic cancer. However, KRAS mutations were detected in pancreatic juice from 19% of controls. Mutations detected in individuals without pancreatic abnormalities, based on imaging analyses, likely arise from small pancreatic intraepithelial neoplasia lesions. ClinicalTrials.gov no: NCT00438906 and NCT00714701.

Sexual risk behaviors and acceptability of HIV pre-exposure prophylaxis among HIV-negative gay and bisexual men in serodiscordant relationships: a mixed methods study.

The objective of this mixed methods study was to examine current sexual risk behaviors, acceptability and potential adoption of pre-exposure prophylaxis (PrEP) for HIV prevention, and sexual behavior intentions with PrEP adoption among HIV-negative gay and bisexual men (GBM) in HIV serodiscordant relationships. A multiracial/ethnic sample of 25 HIV-negative GBM in serodiscordant relationships completed a qualitative interview and a brief interviewer-administered survey. A modified grounded theory approach was used to identify key themes relating to acceptability and future adoption of PrEP. Participants reported engaging in sexual risk behaviors that place them at risk for HIV infection. Participants also reported a high level of acceptability for PrEP and willingness to adopt PrEP for HIV prevention. Qualitative themes explaining future PrEP adoption included: (1) the opportunity to engage in sex using a noncondom HIV prevention method, (2) protection from HIV infection, and (3) less anxiety when engaging in sex with an HIV-positive partner. Associated with the future adoption of PrEP, a majority (64%) of participants indicated the likelihood for an increase in sexual risk behaviors and a majority (60%) of participants also indicated the likelihood for a decrease or abandonment of condom use, both of which are in contrast to the findings from the large iPrEx study. These findings suggest that the use of PrEP by HIV-negative GBM in serodiscordant relationships carries with it the potential for risk compensation. The findings suggest that PrEP only be offered as part of a comprehensive HIV prevention strategy that includes ongoing risk reduction counseling in the delivery of PrEP to help moderate risk compensation.

Screening and management of anal dysplasia and anal cancer in HIV-infected patients: a guide for practice.

People living with HIV infection have a significantly higher rate of anal cancer as compared with that of uninfected people. It is believed that high-grade anal dysplasia secondary to human papillomavirus infection is a precursor to anal cancer. Considering this, screening and treatment of high-grade anal dysplasia is a possible means of preventing the development of anal cancer. No national or international guidelines exist to guide practice for screening and management of anal dysplasia. On the basis of a review of research and expert recommendations, a guide to practice for screening and management of anal dysplasia and anal cancer is made for clinicians.

Condom attitudes, perceived vulnerability, and sexual risk behaviors of young Latino male urban street gang members: implications for HIV prevention.

We examined condom attitudes, perceived vulnerability to HIV, HIV testing experiences, and sexual and substance use risk behaviors of 161 active Latino male gang members, aged 18-26 years old, living in Los Angeles, California. Gang members reported negative condom attitudes and a perceived vulnerability to HIV. The majority (53%) of gang members reported unprotected vaginal intercourse (UVI) in the previous 12 months. Multivariate analyses indicated that participants who engaged in the following behaviors were more likely to report UVI: had sex with someone they just met (adjusted odds ratio [AOR] = 3.66), received money or drugs for sex (AOR = 5.05), or had sex with someone who had a sexually transmitted disease (AOR = 4.99). Participants with a higher perceived vulnerability to HIV were less likely to report UVI (AOR = 0.82). Our findings offer implications for development of an HIV prevention intervention for Latino male gang members.