Identifying Dementia Risk in Older Veterans Using A Mailing Survey.

Evidence suggests that dementia can be prevented. Patients with frailty may be particularly at risk for cognitive impairment (CI). The aim of this study was to determine dementia risk in older Veterans and whether the risk varies according to frailty status. We also evaluated the feasibility of mailed dementia risk screening. Participants were mailed a questionnaire and the Self-Administered Gerocognitive Examination (SAGE). High dementia risk was defined as having mild cognitive impairment (MCI) on SAGE or a CAIDE score ≥6. Out of 5,432 mailed surveys, we obtained a response rate of 19.75%. Most responders completed the questionnaire items. We identified a total of 689 (75.9%) subjects to be at high risk for dementia. Individuals with frailty were at a greater risk for dementia when compared to robust individuals OR:1.921 (95%CI:1.259-2.930), p=.002. The mailed screening represents a convenient, alternative and scalable approach to screen for dementia risk.

Identification of nanoscale dissipation processes by dynamic atomic force microscopy.

Identification of energy-dissipation processes at the nanoscale is demonstrated by using amplitude-modulation atomic force microscopy. The variation of the energy dissipated on a surface by a vibrating tip as a function of its oscillation amplitude has a shape that singles out the dissipative process occurring at the surface. The method is illustrated by calculating the energy-dissipation curves for surface energy hysteresis, long-range interfacial interactions and viscoelasticity. The method remains valid with independency of the amount of dissipated energy per cycle, from 0.1 to 50 eV. The agreement obtained between theory and experiments performed on silicon and polystyrene validates the method.

Effects of a cognitive-behavioral HIV prevention intervention among HIV negative male substance abusers in VA residential treatment.

This investigation compared the effectiveness of a cognitive-behavioral HIV risk reduction intervention with a standard care (SC) comparison condition in modifying HIV risk related knowledge, beliefs, attitudes, and behavior at 6-month and 12-month follow-ups among 149 HIV seronegative males. The two intervention conditions were administered while participants were in inpatient alcohol and other drug abuse treatment. Global drug abuse severity, as well as injection drug abuse, decreased significantly from preintervention to follow-up across conditions. There were significant increases in the proportions reporting sexual activity and increases in levels of unprotected sex acts between baseline and follow-up across conditions. However, no changes in sex risk behavior were found among those who reported sexual activity both prior to and after intervention across conditions. Participants revealed relatively adequate knowledge regarding HIV and HIV risk reduction practices, strong belief in the utility of safer practices and in their ability to enact such practices, and relatively strong commitment to practice safer sex across conditions at baseline assessment. In general, substantial postintervention improvements over baseline levels in these areas were not found. Relatively modest changes in sexual self-efficacy and in safe-sex guidelines were identified in analyses involving the total sample. Exploratory subgroup analysis suggested increases in knowledge and reductions in susceptibility and anxiety among those who reported sexual activity both prior to and after intervention. Among participants reporting initiation of sexual activity after intervention, those receiving SC revealed changes in perceived susceptibility and in condom attitudes. A discussion is presented of challenges associated with providing meaningful HIV risk reduction intervention when baseline levels of sex risk behavior, perceived HIV infection susceptibility, and HIV anxiety are only moderate and when initial levels of sexual self-efficacy and commitment are relatively high.

Adherence, side effects and efficacy of stavudine plus lamivudine plus nelfinavir in treatment-experienced HIV-infected patients.

OBJECTIVES: To evaluate adherence, side effects and efficacy of a modality of highly active antiretroviral therapy (HAART) in HIV-infected patients. METHODS: In a cohort, prospective study, 65 previously treated patients received stavudine plus lamivudine plus nelfinavir. Fifty-three participants (81%) had a history of intravenous drug use. Patients were evaluated at 3-month intervals. The association of adherence with demographic variables, hepatitis C virus infection, number of stopped antiretroviral regimens, HIV RNA level, CD4 cell count, and adverse effects to drugs was assessed. RESULTS: After a median follow-up of 12 months, 30 participants (46%) showed adequate adherence in all visits. An association was observed between adherence and female sex: 18 of 47 men (38%) vs. 12 of 18 women (67%) presented adequate adherence in all visits (P=0. 0416). An association was also observed between adherence and low baseline HIV RNA level (P=0.0229). Discontinuation of treatment took place because of refusal to take medication in 11 participants (17%) and because of side effects in seven participants (11%). Undetectable HIV RNA level was achieved in 26 patients (40%) at 3 months and in lower percentages at months 6, 9 and 12. CONCLUSIONS: Overall adherence to the employed HAART regimen was poor. Female sex and low baseline HIV RNA were associated with better adherence. Refusal to take medications and side effects were the main reasons to stop therapy. At 3 months' follow-up, virological efficacy was achieved in 40% of patients.

A randomized, comparative study of lamivudine plus stavudine, with indinavir or nelfinavir, in treatment-experienced HIV-infected patients.

OBJECTIVE: To compare adherence and clinical outcome with two modalities of highly active antiretroviral therapy (HAART), in HIV-infected patients. DESIGN: Randomized, open-label, prospective study. SETTING: Tertiary care centre in Spain. PATIENTS: A total of 112 non-naive HIV-infected patients, recruited from March 1998 through August 1998, were studied. INTERVENTIONS: Triple drug therapy with stavudine and lamivudine, plus indinavir or nelfinavir. MAIN OUTCOME MEASURES: Adherence, side-effects, and immunological, virological, and clinical efficacy of treatment were assessed at 3-month intervals. RESULTS: After a median follow-up of 9 months, 32% of patients in the indinavir group versus 50% of those in the nelfinavir group showed adequate adherence in all clinical appointments (P= 0.0559). Adherence was superior in the nelfinavir group in every visit. After 6 months of treatment 48% of subjects in the indinavir group and 70% of those in the nelfinavir group exhibited adequate adherence (P= 0.0311). After 9 months 35% of patients in the indinavir group and 59% of those in the nelfinavir group showed adequate adherence (P= 0.0291). Side-effects provoked discontinuation of treatment in 34% of patients in the indinavir group and 12% of patients in the nelfinavir group (P= 0.0073). Immunological and virological efficacy were similar in both groups. CONCLUSIONS: Adherence to a HAART regimen with stavudine plus lamivudine plus nelfinavir was superior to a regimen with stavudine plus lamivudine plus indinavir. Side-effects provoked more discontinuation of treatment in the indinavir group than in the nelfinavir group.

Stavudine, lamivudine and indinavir in drug abusing and non-drug abusing HIV-infected patients: adherence, side effects and efficacy.

OBJECTIVES: To compare adherence and clinical outcome with highly active antiretroviral therapy (HAART) in intravenous drug users (IDUs) and subjects with other HIV risk behaviours (non-IDUs). METHODS: A total of 133 non-naive HIV-infected patients, 95 (71%) IDUs and 38 (29%) non-IDUs received triple drug therapy with stavudine, lamivudine, and indinavir. Adherence, side effects, and immunological and virological efficacy of treatment were assessed every 3 months. RESULTS: During a median follow-up of 12 months, 43 patients (32% of the total) showed adequate adherence in all clinical appointments. Adherence was superior in non-IDUs than in IDUs in every visit, but a significant difference was found only at 6 months, when 22 (58%) non-IDUs versus 37 (39%) IDUs were adherent (P = 0.047). Mildly increased bilirubin was observed in 69 (52%) patients, and renal colic in 34 (26%). No difference in side effects was found between IDUs and non-IDUs. After 6 months of treatment, 35 (43%) participants presented a CD4 cell count increase >100x10(6)/l, and 47 (58%) achieved undetectable HIV RNA (lower limit of detection: 200 copies/ml). CD4 cell count and HIV RNA responses were similar in both groups. CONCLUSIONS: Adherence to the employed HAART regimen was poor. Non-IDUs were more adherent than IDUs, but the difference between both groups was small. Side effects and efficacy were similar in IDUs and non-IDUs.

DNA synthesis during hormone-dependent mammary tumor regression in rats.

A serial biopsy method was developed to study DNA synthesis in 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors during the regression process induced by bromocryptine (CB-154) administration in highly inbred female SD rats. With this technique the changes in tumor size could be correlated with those of DNA synthesis in single regressing tumors. DNA synthesis was estimated by the in vitro incorporation of tritiated thymidine into DNA which correlated well (correlation coefficient r = 0.95) with the in vivo mitotic activity of these neoplasms. Neither the biopsies themselves nor the estral status of the hosts affected significantly the rate of tumor DNA synthesis. DNA synthesis decreased sharply 4-8 days after the beginning of CB-154 treatment, whereas tumor shrinkage occurred more gradually. In conclusion, the serial biopsy method is a reliable technique for the estimation of changes in DNA synthesis in regressing DMBA-induced rat mammary tumors, whereas the measurement of the rate of tumor shrinkage is not.

Effects of bovine growth hormone on RNA synthesis in brain and liver of neonatal hypothyroid rats.

The action of growth hormone upon RNA synthesis was studied in isolated nuclei from cerebrum and liver of hypothyroid rats. The acute administration of bovine growth hormone (bGH) to cretinoid rats, 10 days after birth, stimulated the endogeneous activity of RNA polymerase I and II in both organs. The transcription of ribosomal RNA in cerebrum and hnRNA in liver increased 40 min. after the injection and continued to be higher than in controls until 14 hrs. An increase in the synthesis of hepatic ribosomal RNA occurred 5 hrs. after treatment, the effect persisting during the whole period studied. The activity of cerebral RNA polymerase II displayed a bimodal curve with an early stimulation at 40 min. and a second one at 14 hrs. The results give evidence in favour of the action of growth hormone during the postnatal development of rat brain.

An electrophoretic analysis of proteolipids from different rat brain subcellular fractions.

Proteolipid proteins were extracted from adult rat brain subcellular fractions and purified by chromatography on Sephadex LH-60. Polyacrylamide gel electrophoresis of the delipidized proteins, in the presence or absence of 8 M urea, was carried out with all fractions. The distribution of the various types of proteolipid proteins was studied and their molecular weight calculated by the Ferguson relationship. Several bands of proteolipid proteins were found in the five membrane fractions analyzed. Some of them, such as the 17.5 K and 37 K components were very prominent in mitochondria and synaptosomes. The 30 K component was found in myelin-derived membranes and in microsomes, while the 20 K and 25 K proteolipid proteins were present in all subcellular fractions. The 30 K component (proteolipid protein (PLP)), typical of the purified myelin membranes, showed a similar distribution to that of 2',3'-cyclic-nucleotide 3'-phosphohydrolase (EC 3.1.4.37) activity, while the other major proteolipid protein present in all subcellular fractions (25 K) did not show such parallelism, indicating that it might not be an exclusive component of myelin. The electrophoretic pattern of microsomal proteolipid proteins did not show the high molecular weight components (aggregates of PLP) which are found in myelin. Furthermore, the 30 K component showed a smaller Y0 value than that of the 30 K found in myelin. Thus the presence of 30 K proteolipid protein in microsomes should not be considered as being due to myelin contamination.

Rapid purification of proteolipids from rat brain subcellular fractions by chromatography on a lipophilic dextran gel.

Proteolipids from adult rat brain subcellular fractions were purified by a one-step procedure involving chromatography through Sephadex LH-60 eluted with an acidified chloroform-methanol mixture. The protein peak was eluted with the void volume and was free of adventitious lipids. The degree of purification was similar to that attained with the neutral-acidified chloroform-methanol dialysis method with the advantage that this new procedure can be carried out in only 3 h, with a recovery of proteins of 95-100%. Samples containing different lipid/protein ratios passed through the gel gave similar elution profiles. When labeled amino acids or palmitic acid were added to myelin total lipid extracts, no radioactivity was eluted with the protein, indicating that the proteolipid apoproteins purified by this method do not adsorb hydrophobic low-molecular-weight compounds.

Thyroid hormones effects on RNA synthesis in brain and liver of neonatal hypothyroid rats.

The effect of replacement therapy with thyroid hormones upon RNA transcription was studied in isolated nuclei of cerebrum and liver from hypothyroid rats. The chronic administration of T4 to hypothyroid rats, from the 5th day of life, during ten days, corrected the RNA synthesis in isolated nuclei from cerebrum and liver. The injection of a single dose of T3 to neonatally thyroidectomized rats, ten days after birth, enhanced the endogeneous activity of RNA polymerase I and II of cerebrum and liver. In cerebrum the transcription of ribosomal RNA increased 40 minutes after T3 injection, this activity being constant during the whole period studied. On the other hand, the synthesis of heterogeneous RNA showed an increase only 5 hrs. after the beginning of the treatment. In liver, the lag period is higher for both enzymes, being the maximal response achieved 5 hs. after the hormonal administration.

Age-dependent changes of uridine nucleotide and RNA metabolism in the brain of normal and hypothyroid rats.

The effects of neonatal thyroidectomy on the incorporation in vivo of labelled orotic acid into acid-soluble uridine nucleotides, nuclear RNA and microsomal RNA of the rat brain were studied at 10 and 30 days of age. It was found that the conversion of orotate into uridine nucleotides is high at the earliest stage and does not change upon maturation. At any stage, the neonatal lack of thyroid function does not effect the conversion of orotate into uridine nucleotides. Neonatal thyroidectomy led to a significant decrease in the synthesis of cerebral RNA only at 10 days after birth.

Age-dependent changes of uridine nucleotide and RNA metabolism in the brain of normal and hypothyroid rats

The effects of neonatal thyroidectomy on the incorporation in vivo of labelled orotic acid into acid-soluble uridine nucleotides, nuclear RNA and microsomal RNA of the rat brain were studied at 10 and 30 days of age. It was found that the conversion of orotate into uridine nucleotides is high at the earliest stage and does not change upon maturation. At any stage, the neonatal lack of thyroid function does not effect the conversion of orotate into uridine nucleotides. Neonatal thyroidectomy led to a significant decrease in the synthesis of cerebral RNA only at 10 days after birth.