First phase viral kinetic parameters as predictors of treatment response and their influence on the second phase viral decline

It has recently been shown that upon initiation of interferon (IFN) treatment there is a biphasic decline in hepatitis C virus (HCV) RNA levels. In preliminary results, the rate of second phase viral decline has been shown to be an excellent predictor of treatment response. In this analysis, we determined whether the first phase viral kinetic parameters affected the rate of second phase viral decline. We also assessed whether first phase viral kinetic parameters could be used to predict treatment response within 24 h of initiating treatment. This study is a retrospective analysis of two completed studies from which detailed kinetic data were obtained in patients infected with genotype 1 HCV. In both studies, viral levels were measured frequently over the first 24 h, allowing the determination of IFNs effectiveness in blocking viral production and the viral load at the end of the first phase (v1). The second phase decline slope was calculated by log-linear regression on measurements of serum HCV RNA during days 2, 7 and 14. In study one, sustained viral response (SVR) rates were obtained, allowing the determination of the first phase's predictive power for SVR. Logistic regression and fisher exact tests were used to analyse data. In study one, no patient achieved SVR without an IFN effectiveness greater than 98% and a V1 less than 250 000 copies/mL. When V1 and IFN effectiveness were combined to predict SVR, a negative predictive value= 100%, positive predictive value=71% and accuracy of 95% was obtained after only 24 h of IFN treatment. Both studies illustrated strong correlations for both IFN effectiveness and V1 with the rate of 2nd phase slope (P < 0.001). V1 also correlated significantly with a calculation of infected cell loss (delta), which is a major determinant of the second phase viral decline. These results suggest that early viral kinetics may predict lack of response after only 24 h of treatment initiation and indicate a strong link between the degree of viral load reduction during the first phase, and the subsequent 2nd phase decline slope. This might be explained by a viral dynamics model assuming a jump-start of the immune response when viral loads are reduced below a threshold, subsequently giving rise to a faster 2nd phase decline slope.     

The cholesterol-regulated StarD4 gene encodes a StAR-related lipid transfer protein with two closely related homologues,StarD5 and StarD6

Using cDNA microarrays, we identified StarD4 as a gene whose expression decreased more than 2-fold in the livers of mice fed a high-cholesterol diet. StarD4 expression in cultured 3T3 cells was also sterol-regulated, and known sterol regulatory element binding protein (SREBP)-target genes showed coordinate regulation. The closest homologues to StarD4 were two other StAR-related lipid transfer (START) proteins named StarD5 and StarD6. StarD4, StarD5, and StarD6 are 205- to 233-aa proteins consisting almost entirely of START domains. These three constitute a subfamily among START proteins, sharing approximately 30% amino acid identity with one another, approximately 20% identity with the cholesterol-binding START domains of StAR and MLN64, and less than 15% identity with phosphatidylcholine transfer protein (PCTP) and other START domains. StarD4 and StarD5 were expressed in most tissues, with highest levels in liver and kidney, whereas StarD6 was expressed exclusively in the testis. In contrast to StarD4, expression of StarD5 and MLN64 was not sterol-regulated. StarD4, StarD5, and StarD6 may be involved in the intracellular transport of sterols or other lipids.     

Residual effects of daytime administration of melatonin on performance relevant to flight

There is a general consensus that melatonin possesses time-dependent hypnotic effects, but there is no information yet whether it has residual effects on neurobehavioral performance, especially after daytime administration. In the present study we investigated the possible residual effects of 3 mg melatonin on performance relevant to flight and on subjective feelings of sleepiness, arousal, activation and affect after a daytime nap, as a function of nap length. Fifteen reserve pilots of the Israeli Air Force participated in the study. The experiment consisted of four sessions during which either melatonin or placebo was administered at 16:00 h. In two conditions, subjects were allowed to sleep for 2 h (17:00-19:00 h) whereas in the other two only a 0.5-h nap was allowed. After the naps they started performing a flight simulator task every 2 h. Sleep efficiency significantly increased and sleep latency significantly decreased in both melatonin conditions compared to placebo. Flight performance was only mildly affected in the 0.5-h nap condition. Subjective assessment of sleepiness significantly differed between the two treatment conditions, only in the 0.5-h nap condition. Subjects felt sleepier 2-4 h after melatonin administration. To conclude, our data suggest that administration of melatonin before a brief daytime nap (about 0.5 h) may be associated with mild residual effects on psychomotor performance and may significantly affect subjective feeling of sleepiness for 2-4 h.     

A practical model for preventing type 2 diabetes in minority youth

PURPOSE: This article proposes a model grounded in behavioral theory and empirical evidence for use when developing a program to prevent type 2 diabetes in high-risk minority youth. METHODS: The model is based on key concepts of 4 behavioral theories: the Health Belief Model, Social Learning Theory, the Theory of Planned Behavior, and the Ecological Model. Determinants of behavior to target for change are selected based on their theoretical link to behavior change, their success in changing behavior in past programs, and through thorough formative research in the target community. RESULTS: Diabetes prevention in children requires modifying a complex set of behavior patterns. Social norms and the environment are especially important in children in whom cognitive processes have not fully developed. Family and community involvement is essential for developing a health program and providing a supportive environment in which to change behavior and ongoing reinforcement to maintain behavior changes. CONCLUSIONS: Behavioral theory informs the selection of factors to target in a behavioral intervention. Special considerations apply when working with children. A program to target risk must be based in behavioral theory, supported by practical data, and tailored to the needs and beliefs of the target community.     

Bilateral plasmacytoma of the breast: a case report

Plasmacytoma of the breast is a rare condition that may occur as a solitary finding or in association with multiple myeloma. Of the cases of plasmacytoma of the breast that have been described, nearly half have been bilateral. We report a case of bilateral plasmacytoma of the breast detected on a routine screening mammogram in a patient with a recent diagnosis of multiple myeloma.     

Embracing computer modeling to address pandemic influenza in the 21st century.

Reacting to a pandemic influenza outbreak will require the mass distribution of vaccine, when available, which will require county health departments to set up and operate one or more mass vaccination clinics, also known as points of dispensing (PODs). Carefully planning these PODs before an event occurs is a difficult but important job. First, this article describes a tool--the Clinic Planning Model Generator computer program--designed to help public health agencies evaluate and make adjustments to their POD plans. The Clinic Planning Model Generator was built on data from a smallpox exercise and other biological agent POD exercises. Second, this article demonstrates the application of the Clinic Planning Model Generator through an example pandemic influenza scenario. This work is the result of an ongoing collaboration between Montgomery County, Maryland's Advanced Practice Center for Public Health Emergency Preparedness and Response, and the Institute for Systems Research at the University of Maryland.     

Blunted hormone responses to Ipsapirone are associated with trait impulsivity in personality disorder patients.

Impulsive aggression is associated with central serotonergic dysfunction. Animal models particularly implicate the 5-HT(1A) receptor in this behavior. We tested the hypothesis that central 5-HT(1A) receptor function is impaired in impulsive aggressive personality disorder patients. A total of 52 individuals with DSM-III-R personality disorders, all medically healthy adult outpatients without concurrent psychiatric medication treatment, underwent serial plasma cortisol, prolactin, and temperature measurements before and after ipsapirone 20 mg oral administration. Subjects completed self-report measures of impulsivity, hostility, depression and anxiety, and childhood maltreatment. Stepwise regression analysis revealed impulsivity alone among symptom measures to be associated with significantly decreased peak cortisol and prolactin responses. Diagnoses of borderline personality disorder (BPD) and intermittent explosive disorder-revised (IED-R) were associated with significantly increased and decreased cortisol responses, respectively. However, post hoc analyses indicated that impulsivity was significantly negatively correlated with cortisol responses in the BPD group, and may mediate the association of both BPD and IED-R with altered cortisol responses. Temperature response was associated with neither diagnostic nor symptom measures. Neither diagnostic nor dimensional measures of depression or anxiety, nor severity of childhood maltreatment, were significantly associated with cortisol, prolactin, or temperature responses. Impulsivity is related to impaired function at (or downstream to) postsynaptic 5-HT(1A) receptors, and this relationship may be partly responsible for the association of impaired serotonergic function with diagnoses such as BPD and IED-R. In addition, D(2) receptor dysfunction may play a role in impulsivity, whereas 5-HT(1A) cell-body autoreceptor function may be spared in these disorders.