Quantitation of Human Seroresponsiveness to Merkel Cell Polyomavirus

Merkel cell carcinoma (MCC) is a relatively uncommon but highly lethal form of skin cancer. A majority of MCC tumors carry DNA sequences derived from a newly identified virus called Merkel cell polyomavirus (MCV or MCPyV), a candidate etiologic agent underlying the development of MCC. To further investigate the role of MCV infection in the development of MCC, we developed a reporter vector-based neutralization assay to quantitate MCV-specific serum antibody responses in human subjects. Our results showed that 21 MCC patients whose tumors harbored MCV DNA all displayed vigorous MCV-specific antibody responses. Although 88% (42/48) of adult subjects without MCC were MCV seropositive, the geometric mean titer of the control group was 59-fold lower than the MCC patient group (p<0.0001). Only 4% (2/48) of control subjects displayed neutralizing titers greater than the mean titer of the MCV-positive MCC patient population. MCC tumors were found not to express detectable amounts of MCV VP1 capsid protein, suggesting that the strong humoral responses observed in MCC patients were primed by an unusually immunogenic MCV infection, and not by viral antigen expressed by the MCC tumor itself. The occurrence of highly immunogenic MCV infection in MCC patients is unlikely to reflect a failure to control polyomavirus infections in general, as seroreactivity to BK polyomavirus was similar among MCC patients and control subjects. The results support the concept that MCV infection is a causative factor in the development of most cases of MCC. Although MCC tumorigenesis can evidently proceed in the face of effective MCV-specific antibody responses, a small pilot animal immunization study revealed that a candidate vaccine based on MCV virus-like particles (VLPs) elicits antibody responses that robustly neutralize MCV reporter vectors in vitro. This suggests that a VLP-based vaccine could be effective for preventing the initial establishment of MCV infection

Prolonged exposure for the treatment of Spanish-speaking Puerto Ricans with posttraumatic stress disorder: a feasibility study

<p>Abstract</p> <p>Background</p> <p>Most of the empirical studies that support the efficacy of prolonged exposure (PE) for treating posttraumatic stress disorder (PTSD) have been conducted on white mainstream English-speaking populations. Although high PTSD rates have been reported for Puerto Ricans, the appropriateness of PE for this population remains unclear. The purpose of this study was to examine the feasibility of providing PE to Spanish speaking Puerto Ricans with PTSD. Particular attention was also focused on identifying challenges faced by clinicians with limited experience in PE. This information is relevant to help inform practice implications for training Spanish-speaking clinicians in PE.</p> <p>Results</p> <p>Fourteen patients with PTSD were randomly assigned to receive PE (n = 7) or usual care (UC) (n = 7). PE therapy consisted of 15 weekly sessions focused on gradually confronting and emotionally processing distressing trauma-related memories and reminders. Five patients completed PE treatment; all patients attended the 15 sessions available to them. In UC, patients received mental health services available within the health care setting where they were recruited. They also had the option of self-referring to a mental health provider outside the study setting. The Clinician-Administered PTSD Scale (CAPS) was administered at baseline, mid-treatment, and post-treatment to assess PTSD symptom severity. Treatment completers in the PE group demonstrated significantly greater reductions in PTSD symptoms than the UC group. Forty percent of the PE patients showed clinically meaningful reductions in PTSD symptoms from pre- to post-treatment.</p> <p>Conclusions</p> <p>PE appears to be viable for treating Puerto Rican Spanish-speaking patients with PTSD. This therapy had good patient acceptability and led to improvements in PTSD symptoms. Attention to the clinicians' training process contributed strongly to helping them overcome the challenges posed by the intervention and increased their acceptance of PE.</p

Elevated Paracellular Glucose Flux across Cystic Fibrosis Airway Epithelial Monolayers Is an Important Factor for Pseudomonas aeruginosa Growth.

People with cystic fibrosis (CF) who develop related diabetes (CFRD) have accelerated pulmonary decline, increased infection with antibiotic-resistant Pseudomonas aeruginosa and increased pulmonary exacerbations. We have previously shown that glucose concentrations are elevated in airway surface liquid (ASL) of people with CF, particularly in those with CFRD. We therefore explored the hypotheses that glucose homeostasis is altered in CF airway epithelia and that elevation of glucose flux into ASL drives increased bacterial growth, with an effect over and above other cystic fibrosis transmembrane conductance regulator (CFTR)-related ASL abnormalities. The aim of this study was to compare the mechanisms governing airway glucose homeostasis in CF and non-CF primary human bronchial epithelial (HBE) monolayers, under normal conditions and in the presence of Ps. aeruginosa filtrate. HBE-bacterial co-cultures were performed in the presence of 5 mM or 15 mM basolateral glucose to investigate how changes in blood glucose, such as those seen in CFRD, affects luminal Ps. aeruginosa growth. Calu-3 cell monolayers were used to evaluate the potential importance of glucose on Ps. aeruginosa growth, in comparison to other hallmarks of the CF ASL, namely mucus hyperviscosity and impaired CFTR-dependent fluid secretions. We show that elevation of basolateral glucose promotes the apical growth of Ps. aeruginosa on CF airway epithelial monolayers more than non-CF monolayers. Ps. aeruginosa secretions elicited more glucose flux across CF airway epithelial monolayers compared to non-CF monolayers which we propose increases glucose availability in ASL for bacterial growth. In addition, elevating basolateral glucose increased Ps. aeruginosa growth over and above any CFTR-dependent effects and the presence or absence of mucus in Calu-3 airway epithelia-bacteria co-cultures. Together these studies highlight the importance of glucose as an additional factor in promoting Ps. aeruginosa growth and respiratory infection in CF disease

EXTRA: Towards the exploitation of eXascale technology for reconfigurable architectures

© 2016 IEEE. To handle the stringent performance requirements of future exascale-class applications, High Performance Computing (HPC) systems need ultra-efficient heterogeneous compute nodes. To reduce power and increase performance, such compute nodes will require hardware accelerators with a high degree of specialization. Ideally, dynamic reconfiguration will be an intrinsic feature, so that specific HPC application features can be optimally accelerated, even if they regularly change over time. In the EXTRA project, we create a new and flexible exploration platform for developing reconfigurable architectures, design tools and HPC applications with run-time reconfiguration built-in as a core fundamental feature instead of an add-on. EXTRA covers the entire stack from architecture up to the application, focusing on the fundamental building blocks for run-time reconfigurable exascale HPC systems: new chip architectures with very low reconfiguration overhead, new tools that truly take reconfiguration as a central design concept, and applications that are tuned to maximally benefit from the proposed run-time reconfiguration techniques. Ultimately, this open platform will improve Europe's competitive advantage and leadership in the field

The use of adherence aids by adults with diabetes: A cross-sectional survey

BACKGROUND: Adherence with medication taking is a major barrier to physiologic control in diabetes and many strategies for improving adherence are in use. We sought to describe the use of mnemonic devices and other adherence aids by adults with diabetes and to investigate their association with control of hyperglycemia, hyperlipidemia and hypertension. METHODS: Cross sectional survey of diabetic adults randomly selected from Primary Care practices in the Vermont Diabetes Information System. We used linear regression to examine the associations between the use of various aids and physiologic control among subjects who used oral agents for hyperglycemia, hypercholesterolemia, and hypertension. RESULTS: 289 subjects (mean age 65.4 years; 51% female) used medications for all three conditions. Adherence aids were reported by 80%. The most popular were day-of-the-week pill boxes (50%), putting the pills in a special place (41%), and associating pill taking with a daily event such as a meal, TV show, or bedtime (11%). After adjusting for age, sex, marital status, income, and education, those who used a special place had better glycemic control (A1C -0.36%; P = .04) and systolic blood pressure (-5.9 mm Hg; P = .05) than those who used no aids. Those who used a daily event had better A1C (-0.56%; P = .01) than patients who used no aids. CONCLUSION: Although adherence aids are in common use among adults with diabetes, there is little evidence that they are efficacious. In this study, we found a few statistically significant associations with adherence aids and better diabetes control. However, these findings could be attributed to multiple comparisons or unmeasured confounders. Until more rigorous evaluations are available, it seems reasonable to recommend keeping medicines in a special place for diabetic adults prescribed multiple medications

Clinico-pathological profile of sinonasal masses: an experience in national ear care center Kaduna, Nigeria

<p>Abstract</p> <p>Background</p> <p>The presence of a mass in the nose and paranasal sinuses may seem to be a simple problem; however it raises many questions about the differential diagnosis. The aim of this study is to evaluate the clinico-pathological profile of sinonasal masses in our environment</p> <p>This is a retrospective analytical review of all the patients with sinonasal masses that presented to the national ear care center, Kaduna over a six year (2003-2008) period. Their biodata, clinical profile and histological diagnoses were analyzed.</p> <p>Findings</p> <p>A total of 76 patients were analyzed, age range 5 to 64 yrs with a mean age of 33.3 yr median and modal age of 35.00 (SD = 13.1 ± 1.5). Majority of the patients were in the age groups 21-50 yrs. There were 34 male and 42 female with M: F ratio of 1:1.2. The main presenting symptoms are nasal blockage 97.4% and rhinorrhea 94.7%. It was bilateral in 34 (44.7%), left side in 24(31.6%) and right side in 18(23.7%) patients. The commonest clinical diagnoses were simple nasal polyp 47(61.8%) and antrochoanal polyp 10(13.2%). About 59 (77.6%) were benign, 2 (2.6%) were malignant and 15 (19.7%) were lost to follow up. The commonest histological diagnosis is simple inflammatory nasal polyp in 28 (36.8%) patients and the least was nasal capillary hemangioma 2 (2.6%). About 55(72.4%) patients had surgical treatment.</p> <p>Conclusions</p> <p>Nasal obstruction and rhinorrhea are the commonest symptoms of presentation, simple inflammatory nasal polyp is still the commonest histological pattern seen in our environment, and surgery is still the best modality of treatment for benign tumor thus the need for advocacy for early recognition and referral to the ENT surgeon.</p

Reducing HIV Risks Among Active Injection Drug and Crack Users: The Safety Counts Program

The efficacy of Safety Counts, a CDC-diffused intervention, was reanalyzed. In a quasi experimental, cross-over design, injection drug users (IDU) and crack users in two neighborhoods were assigned by neighborhood to receive individual Voluntary HIV Counseling and Testing or Safety Counts and 78% were reassessed at 5–9 months. Drug users in the Safety Counts program reported significantly greater reductions in risky sex, crack and hard drug use, and risky drug injection. The more sessions of Safety Counts attended, the greater were the reductions in risky acts. Different analytic decisions result in very different findings for the same intervention. Safety Counts is an effective intervention for IDU and crack users. Analytic decision of intervention outcomes is highly related to evaluations of an intervention’s efficacy