Hepatitis C virus-related complications are increasing in women veterans: A national cohort study.

There are gender-specific variations in the epidemiology and clinical course of hepatitis C virus (HCV) infection. However, few long-term longitudinal studies have examined trends in the incidence and prevalence of serious liver complications among women compared with men with HCV infection. We used the Veterans Administration Corporate Data Warehouse to identify all veterans with positive HCV viraemia from January 2000 to December 2013. We calculated gender-specific annual incidence and prevalence rates of cirrhosis, decompensated cirrhosis and hepatocellular cancer (HCC) adjusting for age, diabetes, HIV and alcohol use. We also calculated the average annual per cent change (AAPC) for each outcome by gender using piecewise linear regression in the Joinpoint software. We identified 264 409 HCV-infected veterans during 2000-2013, of whom 7162 (2.7%) were women. There were statistically significant increases over time in the incidence rates of cirrhosis, decompensated cirrhosis and HCC for both men and women. The annual-adjusted incidence rates of cirrhosis, decompensated cirrhosis and HCC were higher in men than women for all study years. However, these complications increased at a similar rate in both groups. Specifically, the AAPC for cirrhosis was 13.1 and 15.2, while it was 15.6 and 16.9 for decompensated cirrhosis and 21.0 and 25.3 for HCC in men and women, respectively (all test of parallelism not significant). The results were similar in the prevalence analyses, although AAPCs were slightly smaller for each outcome. In conclusion, we found an ongoing upward trend in the incidence and prevalence of HCV complications in this cohort of HCV-infected women. This increase in cirrhosis complications in women with active HCV infection is similar to those in men. With cure from HCV now becoming a reality, most of the projected burden of HCV is potentially preventable. However, benefits of HCV treatment will need to extend to all patients in order to stem the rising tide of HCV complications.

The carbon footprint of acute care: how energy intensive is critical care?

OBJECTIVES: Climate change has the potential to threaten human health and the environment. Managers in healthcare systems face significant challenges to balance carbon mitigation targets with operational decisions about patient care. Critical care units are major users of energy and hence more evidence is needed on their carbon footprint. STUDY DESIGN: The authors explore a methodology which estimates electricity use and associated carbon emissions within a Critical Care Unit (CCU). METHODS: A bottom-up model was developed and calibrated which predicted the electricity consumed and carbon emissions within a CCU based on the type of patients treated and working practices in a case study in Cornwall, UK. RESULTS: The model developed was able to predict the electricity consumed within CCU with an error of 1% when measured against actual meter readings. Just under half the electricity within CCU was used for delivering care to patients and monitoring their condition. CONCLUSIONS: A model was developed which accurately predicted the electricity consumed within a CCU based on patient types, medical devices used and working practice. The model could be adapted to enable it to be used within hospitals as part of their planning to meet carbon reduction targets.

Pro-inflammatory chemokine C-C motif ligand 16 (CCL-16) dysregulation in irritable bowel syndrome (IBS): a pilot study.

BACKGROUND: Irritable bowel syndrome (IBS) is a serious health problem that affects an estimated 10-15% of people worldwide and has economic consequences in the United States of over $30 billion annually. In the US, IBS affects all races and both sexes, with more females than males (2:1) reporting symptoms consistent with IBS. Although the etiology of this functional gastrointestinal disorder is unknown, literature suggests that a subclinical inflammatory component has a role in the etiologic mechanisms underlying IBS. The aim of this study was to evaluate the gene expression of inflammatory biomarkers in patients with and without IBS and among different IBS phenotypes. METHODS: Irritable bowel syndrome patients (n=12) that met Rome III Criteria for IBS longer than 6months were compared with healthy matched controls (n=12). Peripheral whole blood from fasting participants was collected and RNA was extracted. The expression of 96 inflammatory genes was then analyzed using a custom quantitative real-time PCR array. KEY RESULTS: CCL-16 gene expression was upregulated by 7.46-fold in IBS patients when compared with controls. CCL-16 was overexpressed by over 130-fold in IBS-constipation patients when compared with both controls and IBS-diarrhea patients. CONCLUSIONS & INFERENCES: These results further suggest a subclinical inflammatory component underlying IBS. To better understand the phenotypic differences in IBS it is important to broaden the study of these inflammatory and other biomarkers.

Medical conditions and symptoms associated with posttraumatic stress disorder in low-income urban women.

BACKGROUND: Epidemiological studies have consistently reported rates of posttraumatic stress disorder (PTSD) in women that are twice that of men. In men and women, PTSD has been associated with comorbid medical conditions, medical symptoms and lower self-rating of health. In low-income urban women, rates of PTSD are even more elevated than in suburban women and may be related to observed health disparities. METHODS: In this study, 250 women seeking healthcare at an urban clinic were interviewed for a PTSD diagnosis, major depressive disorder (MDD), the experience of traumatic events, the experience of current and past common medical conditions and symptoms, and subjective rating of health. A chart review was used to assess healthcare use in the past year. RESULTS: More current (5.2 vs. 3.8, p < 0.05) and past medical conditions (4.6 vs. 3.3, p < 0.05) were reported by women with a lifetime history of PTSD than by women without this history, after controlling for demographics and current depression. Women with lifetime PTSD also had more annual clinic appointments (5.9 vs. 3.8 p < 0.03) and were 2.4 times (p < 0.05) more likely to report lower appraisal of their physical health. CONCLUSIONS: These findings suggest that urban health-seeking women with PTSD experience health impairments that may cause increased morbidity and that healthcare providers should consider the health ramifications of PTSD when providing medical care to women.

Physicochemical factors affecting the rapid bactericidal efficacy of the phenolic antibacterial triclosan.

The antimicrobial activity of triclosan (TCS; 2,4,4'-trichloro-2'-hydroxydiphenyl ether) in aqueous solutions is shown to directly depend upon two key physicochemical parameters: % saturation and saturation solubility. Saturated solutions of TCS in water, water-propylene glycol (PG) mixtures, and aqueous surfactant systems are shown to effect rapid, potent bacterial reductions (e.g. >4 log(10) reduction of Staphylococcus aureus in 15 s contact time in a time kill suspension test). In surfactant solutions, increasing the surfactant: TCS ratio causes a decrease in antibacterial efficacy, consistent with a model for micellar solubilization where the micelle binding constant, K (=X/c(w)) increases with decreasing TCS concentration in the micelles (X), resulting in decreased concentration of bioavailable TCS in the water (continuous) phase (c(w)). The rapid and potent reductions of bacteria reported here were surprising and support the existence of a non-specific mode of action for TCS, such as gross membrane disruption, in addition to the specific modes of action reported by others.

Disposition of CP-671, 305, a selective phosphodiesterase 4 inhibitor in preclinical species.

1. The disposition of (+)-2-[4-({[2-(benzo[1,3] dioxol-5-yloxy)-pyridine-3-carbonyl]-amino)-methyl)-3-fluoro-phenoxyl-propionic acid (CP-671,305), a potent and selective inhibitor of phosphodiesterase 4 (subtype D), was characterized in several animal species in support of its selection for preclinical safety studies and potential clinical development. 2. CP-671,305 demonstrates generally favourable pharmacokinetic properties in all species examined. Systemic plasma clearance after intravenous administration was low in Sprague-Dawley rats (9.60+/-1.16 ml min(-1) kg(-1)), beagle dogs (2.90+/-0.81 ml min(-1) kg(-1)) and cynomolgus monkeys (2.94+/-0.87ml min(-1) kg(-1)) resulting in plasma half-lives > 5 h. Moderate to high bioavailability in rats (43-80%), dogs (45%) and monkeys (26%) was observed after oral dosing. In rats, oral pharmacokinetics were dose dependent over the dose range studied (10 and 25 mgkg(-1)). 3. CP-671,305 was > 97% bound to plasma proteins in rat, dog, monkey and human. 4. The principal route of clearance of CP-671,305 in rats and dogs was by renal and biliary excretion of unchanged drug. This finding was consistent with CP-671,305 resistance towards metabolism in hepatocytes and NADPH-supplemented liver microsomes from preclinical species and human. 5. CP-671,305 did not exhibit competitive inhibition of the five major cytochrome P450 enzymes, namely CYP1A2, 2C9, 2C19, 2D6 and 3A4 (IC50's > 50 microM). Likewise, no time-dependent inactivation of the five major cytochrome P450 enzymes was discernible with CP-671,305. 6. Overall, the results indicate that the absorption, distribution, metabolism and excretion (ADME) profile of CP-671,305 is relatively consistent across preclinical species and predict potentially favourable pharmacokinetic properties in humans, supporting its selection for toxicity/safety assessment studies and possible investigations in humans.

Naming the color of a word: is it responses or task sets that compete?

Subjects named the colors in which high- and low-frequency words and pronounceable nonwords, otherwise matched, were displayed. Color naming was slower for all three item types than for visually equivalent strings of nonalphanumeric symbols but was no slower for words than for nonwords, nor for high-frequency words than for low-frequency words. Unpronounceable letter strings had intermediate color-naming latencies. However, frequency and lexical status had large effects on latency for reading the same words and pseudowords aloud. Interference is thus predicted not by the strength of association between a letter string and its pronunciation but by the presence of word-like constituents. We argue that the interference from an unprimed noncolor word is due to, and isolates, one of two components of the classic Stroop effect: competition from the whole task set of reading. The other component, response competition, occurs only when lexical access is sufficiently primed.

Biological properties of herpes simplex virus 2 replication-defective mutant strains in a murine nasal infection model.

We used a mouse nasal model of herpes simplex virus 2 (HSV-2) infection to examine the biological properties of HSV-2 wild-type (wt), TK-negative, and replication-defective strains in vivo. Nasal septa tissue is the major site of wt viral replication post intranasal (i.n.) inoculation. The HSV-2 strain 186 syn(+)-1 wt virus caused lethal encephalitis at doses of 10(4) PFU and above per nostril, and at lower doses no neurons in the trigeminal ganglia were positive for the latency-associated transcript, indicating a lack of latent infection. The 186DeltaKpn TK-negative mutant virus replicated in nasal septa tissue but showed low-level replication in trigeminal ganglia at only one timepoint. In situ hybridization of trigeminal ganglia showed that the number of LAT-positive neurons was proportional to the inoculum dose from 10(3) to 10(6) PFU per nare. The replication-defective mutant virus 5BlacZ showed no replication in nasal septa tissue and no persistence of viral DNA at the inoculation site or the trigeminal ganglia. Nevertheless, inoculation of 5BlacZ or the double-mutant dl5-29 at distal sites reduced acute replication and latent infection of 186DeltaKpn following intranasal challenge. This infection model provides a biological system to test the properties of HSV-2 strains and shows that replication-defective mutant strains do not persist at sites of inoculation or in sensory ganglia but can induce immune protection that reduces the latent viral load of a challenge virus.

Treatment of a thyrotropinoma with octreotide-LAR in a patient with multiple endocrine neoplasia-1.

OBJECTIVE: To note that a thyrotropin (TSH)-secreting macroadenoma may be part of the multiple endocrine neoplasia-1 (MEN-1) syndrome and to report the use of octreotide-LAR (OCT-LAR) to treat a TSH-secreting macroadenoma in a patient with MEN-1 with previous surgery for hyperparathyroidism and gastrinoma. METHODS: We present a patient with a TSH-secreting pituitary macroadenoma and report the results of her endocrine, genetic, radiologic, and nuclear medicine testing and her response to treatment with octreotide (OCT), octreotide-LAR, and estrogen. RESULTS: This patient's TSH-induced hyperthyroidism responded to octreotide for 5 months and octreotide-LAR for more than 11 months. Her hypercalcemia normalized while she was taking estrogen. Her genetic testing is reported to show a genetic defect that is typical of patients with MEN-1. CONCLUSION: This report describes: (1) The use of octreotide-LAR to treat both a TSH-secreting pituitary tumor and a gastrinoma over 12 months; (2) the importance of including these tumors into the MEN-1 syndrome with its attendant implications; and (3) a genetic defect, typical of patients with MEN-1, associated with this tumor.

A dominant-negative herpesvirus protein inhibits intranuclear targeting of viral proteins: effects on DNA replication and late gene expression.

The d105 dominant-negative mutant form of the herpes simplex virus 1 (HSV-1) single-stranded DNA-binding protein, ICP8 (d105 ICP8), inhibits wild-type viral replication, and it blocks both viral DNA replication and late gene transcription, although to different degrees (M. Gao and D. M. Knipe, J. Virol. 65:2666-2675, 1991; Y. M. Chen and D. M. Knipe, Virology 221:281-290, 1996). We demonstrate here that this protein is also capable of preventing the formation of intranuclear prereplicative sites and replication compartments during HSV infection. We defined three patterns of ICP8 localization using indirect immunofluorescence staining of HSV-1-infected cells: large replication compartments, small compartments, and no specific intranuclear localization of ICP8. Cells that form large replication compartments replicate viral DNA and express late genes. Cells that form small replication compartments replicate viral DNA but do not express late genes, while cells without viral replication compartments are incapable of both DNA replication and late gene expression. The d105 ICP8 protein blocks formation of prereplicative sites and large replication compartments in 80% of infected cells and formation of large replication compartments in the remaining 20% of infected cells. The phenotype of d105 suggests a correlation between formation of large replication compartments and late gene expression and a role for intranuclear rearrangement of viral DNA and bound proteins in activation of late gene transcription. Thus, these results provide evidence for specialized machinery for late gene expression within replication compartments.

How the propagation of error through stochastic counters affects time discrimination and other psychophysical judgments.

The performance of fallible counters is investigated in the context of pacemaker-counter models of interval timing. Failure to reliably transmit signals from one stage of a counter to the next generates periodicity in mean and variance of counts registered, with means power functions of input and standard deviations approximately proportional to the means (Weber's law). The transition diagrams and matrices of the counter are self-similar: Their eigenvalues have a fractal form and closely approximate Julia sets. The distributions of counts registered and of hitting times approximate Weibull densities, which provide the foundation for a signal-detection model of discrimination. Different schemes for weighting the values of each stage may be established by conditioning. As higher order stages of a cascade come on-line the veridicality of lower order stages degrades, leading to scale-invariance in error. The capacity of a counter is more likely to be limited by fallible transmission between stages than by a paucity of stages. Probabilities of successful transmission between stages of a binary counter around 0.98 yield predictions consistent with performance in temporal discrimination and production and with channel capacities for identification of unidimensional stimuli.

Differential attrition rates and active parental consent.

Active parental consent in survey research poses ethical and practical concerns. One common argument against the requirement of active consent procedures is its effect on participation rates. There is additional concern that higher risk groups may be underrepresented in the final sample. Empirical support of differential attrition, however, is lacking. In the current multisite longitudinal study, passive consent procedures were approved for the collection of pretest data. For subsequent years of data collection, active parental consent procedures were required. In this article, we use the pretest data to examine demographic, attitudinal, and behavioral differences between those students for whom active consent was provided and those for whom active consent was either denied or for whom no response was received. The results indicate that active consent procedures produce deleterious effects on participation rates and lead to an underrepresentation of at-risk youth in the sample.

Reality check. Evaluating a school-based gang prevention model.

The Gang Resistance Education and Training (G.R.E.A.T.) program is a school-based gang prevention initiative developed in 1991 through the collaborative efforts of the Bureau of Alcohol, Tobacco, and Firearms, the Federal Law Enforcement Training Center, and the Phoenix Police Department. Uniformed law enforcement officers, certified as G.R.E.A.T. instructors, teach the 9-week curriculum to middle students. In 1994, the National Institute of Justice funded a national evaluation of the G.R.E.A.T. program. The process evaluation component of this larger study is reported. First, results of on-site observations of the G.R.E.A.T. Officer Training program, including an overview of the training activities, and the authors' assessment of the training process are reported. Second, observations of the implementation of the program by officers at six sites are reported. Of primary concern was whether the program delivered to students was similar to the program taught to the officers during the G.R.E.A.T. Officer Training.

Effect of palytoxin on endothelium-dependent and -independent relaxation in rat aortic rings.

Endothelium-intact rat aortic rings were incubated with palytoxin (PTX, 10(-11)-10(-9)M, 10 min) in oxygenated (O2 95%, CO2 5%) baths. Phenylephrine (PE)-contracted vascular rings demonstrated decreasing relaxation to acetylcholine (ACh), depending upon PTX incubation in a dose-dependent manner; however, sodium nitroprusside (NaNP) persisted in returning the ring to its pre-PE tension. After incubation with PTX, relaxation to the receptor-independent, endothelium-dependent relaxant A23187 was also attenuated. Thus, endothelium-dependent mechanism(s) normally responsive to both ACh and A23187, stimulators of nitric oxide (NO) release, were disrupted. Following incubation with PTX, endothelium-independent relaxation to NaNP remained intact but relaxation to atriopeptin II (APII) decreased. Electron microscopy demonstrated microvesiculation of endothelial cell cytoplasm and an irregular luminal surface following incubation with PTX. The intact response to NaNP, despite the loss of relaxation to ACh, indicated that soluble guanylate cyclase was not affected by PTX. However, loss of relaxation to AP-II, involving particulate guanylate cyclase of vascular smooth muscle (VSM), was inhibited by PTX pre-incubation. Determination of the site(s) of action of PTX requires further study.

Non-specific binding of palytoxin to plastic surfaces.

The changes in blood pressure induced by palytoxin (PTX) administered intravenously through polyethylene (PE) tubing were varied, suggesting either non-specific binding of the toxin to PE or deactivation. By spectrophotometry and HPLC, we found that PTX bound non-specifically to PE tubing and that this binding was attenuated by adding 0.1% rat serum albumin. Furthermore, the chemical stability and activity of PTX were not affected by exposure to room light and/or room temperature. Biological deactivation was excluded as a cause of the observed variability because the hypertensive and lethal effects of infused PTX, delayed with simultaneous administration of sodium nitroprusside (NNP), were in full evidence when the NNP was discontinued 35 min later.

Clinical and epidemiological features of neurotoxic shellfish poisoning in North Carolina.

BACKGROUND: In October 1987, a red tide due to P. brevis affected the North Carolina coast for the first time. The purpose of our study was to describe the clinical and epidemiological features of neurotoxic shellfish poisoning (NSP), an illness caused by eating shellfish contaminated with the neurotoxins of P. brevis. METHODS: Active surveillance was established for cases of NSP. A descriptive study of the NSP cases was then completed. RESULTS: Forty-eight persons, who had eaten oysters at 20 meals, met the case definition. A variety of gastrointestinal tract and neurological symptoms were reported. The illnesses were generally mild and of short duration, and there were no deaths. Forty-one (85 percent) affected persons lived in five communities located within a 70-kilometer area along the coast. Cases occurred from October 27 to December 9; 27 (56 percent) of the cases occurred before the first closure of affected shellfish waters on November 2. There was a significant increase in the illness attack rate with an increase in the number of oysters eaten. CONCLUSIONS: Routine monitoring of coastal waters for P. brevis is needed to facilitate earlier recognition of red tides, closure of affected areas, and education of the public before substantial exposure to contaminated shellfish occurs.

Surface characteristics of glass-ionomer cements when treated with cavity varnish.

Two glass-ionomer cements were evaluated. Sixty molds were prepared, 20 with a lining cement, 20 with a base cement, and 20 with a control cement. The samples were tested for hardness; the glass-ionomer materials proved to be significantly harder than the control.

Pineal function in burns: melatonin is not a marker for general sympathetic activity.

Burn injury in humans or rats is a model of marked elevation of general sympathetic activity for weeks, manifested in part by increased heart rate, metabolic rate, core temperature, and plasma and urinary catecholamines. Plasma melatonin was sampled at 2-h intervals for 24 h in 9 control subjects and 11 patients with severe burn injury. Daytime melatonin was not different between the groups, but nighttime values were significantly lower in the burn patients. A nocturnal surge was still significant in the patients. Resting heart rate and rectal temperature were elevated in the burn patients. In male Sprague-Dawley rats, pineal melatonin content did not differ between controls and those with an experimental burn at 4 h into the light phase nor during the nocturnal surge. Male Syrian hamsters with burns had lower daytime pineal melatonin content than did controls, but the nocturnal surge in pineal melatonin was not significantly different between groups, nor was daytime morning serum melatonin. Sympathetic activity appears partitioned, with that controlling melatonin (nocturnal surge) regulated independently. In agreement with our previous findings in other models, melatonin is not a marker for general sympathetic activity, even following severe burn injury.