Comparison of effects on low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with rosuvastatin versus atorvastatin in patients with type IIa or IIb hypercholesterolemia.

This randomized, double-blind, placebo-controlled trial was conducted in 52 centers in North America to compare the effects of the new, highly effective statin, rosuvastatin, with atorvastatin and placebo in hypercholesterolemic patients. After a 6-week dietary run-in, 516 patients with low-density lipoprotein (LDL) cholesterol > or =4.14 mmol/L (160 mg/dl) and < 6.47 mmol/L (250 mg/dl) and triglycerides < or =4.52 mmol/L (400 mg/dl) were randomized to 12 weeks of once-daily placebo (n = 132), rosuvastatin 5 mg (n = 128), rosuvastatin 10 mg (n = 129), or atorvastatin 10 mg (n = 127). The primary efficacy end point was percent change in LDL cholesterol. Secondary efficacy variables were achievement of National Cholesterol Education Program (NCEP) Adult Treatment Panel II (ATP II), ATP III, and European Atherosclerosis Society LDL cholesterol goals and percent change from baseline in high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, non-HDL cholesterol, apolipoprotein B, and apolipoprotein A-I. Rosuvastatin 5 and 10 mg compared with atorvastatin 10 mg were associated with greater LDL cholesterol reductions (-40% and -43% vs 35%; p <0.01 and p <0.001, respectively) and HDL cholesterol increases (13% and 12% vs 8%, p <0.01 and p <0.05, respectively). Total cholesterol and apolipoprotein B reductions and apolipoprotein A-I increases were also greater with rosuvastatin; triglyceride reductions were similar. Rosuvastatin 5 and 10 mg were associated with improved achievement in ATP II (84% in both rosuvastatin groups vs 73%) and ATP III (84% and 82% vs 72%) LDL cholesterol goals, and rosuvastatin 10 mg was more effective than atorvastatin in achieving European Atherosclerosis Society LDL cholesterol goals. Both treatments were well tolerated.     

Antifeedant and Insecticidal Activity of Plant Extracts Against <Emphasis Type="Italic">Spodoptera litura</Emphasis> (Fab.) and <Emphasis Type="Italic">Lipaphis erysimi</Emphasis>

The solvent extracts of four plants, viz. Polyalthia longifolia (Sonn.) Thw. (PL), Paederia foetida (PF), Limonia acidissima L. (LA) and Balanites aegyptiaca (L.) Del. (BA), from different families, were screened for their antifeedant, insecticidal and insect growth regulatory potential against important crop pests. The solvent extracts, namely methanol, petroleum ether, chloroform and water, of all four plants were tested for their bio-activity against lepidopteran insect pest, Spodoptera litura; and sucking insect pest, L. erysimi (mustard aphid). It was observed that Polyalthia longifolia (methanol extract) exhibited maximum potency with least concentration of 0.1 % (~1080 ppm) to give 50 % antifeedancy, followed by P. longifolia (petroleum ether) with a value of 0.2 % (~2360 ppm) and Limonia acidissima (methanol) and L. acidissima (petroleum ether). The least active compound for antifeedancy was found in the aqueous extract of Balanites aegyptica. Out of 16 plant extracts bio-assayed, methanol showed potential antifeedancy when compared with chloroform, water and petroleum ether extracts. But chloroform and petroleum ether extracts of all four plants gave very promising insecticidal activity against aphids, in comparison to other two extracts. L. acidissima (water), B. aegyptica (methanol), P. longifolia (methanol) and P. foetida (water) did not give any insecticidal activity with 50 % lethal concentration (LC₅₀) up to 0.1 % as maximum concentration.     

The effect of Baroque music on behavioural disturbances in patients with dementia

Aim: To study the effect of Baroque music in people with dementia. Methods: Patients in a multicultural dementia‐specific aged care facility were subjected to Baroque music in a cross‐over study. Results: There were significantly more behavioural disturbances during the weeks when Baroque music was played compared to control periods (0.2 more episodes per week, P= 0.01), and more episodes in the afternoon shift compared to evening shift (1 more episode per week, P= 0.001). Conclusion: These results confirm that music can influence behaviour but is contrary to previous results.     

Serum placental growth factor as a predictor of early onset preeclampsia in overweight/obese pregnant women

The purpose of this study was to analyze whether maternal serum placental growth factor (PlGF) could predict early onset preeclampsia (<32 weeks of gestation) in overweight/obese pregnant women, and whether it could do it more effectively than in normal/underweight pregnant women. A prospective cohort study was conducted on 1678 pregnant women with singleton pregnancies, who were grouped as underweight, normal, overweight, and obese on the basis of body mass index, followed by serum PlGF estimation at 20 to 22 weeks of gestation. A cut-off value of <144 pg/mL for PlGF was determined by Receiver Operating Characteristic curve analysis to identify risk of early onset preeclampsia. Univariate logistic regression analysis revealed significantly stronger association between PlGF <144 pg/mL and early onset preeclampsia in overweight/obese pregnant women (odds ratio 7.64; 95% confidence interval 5.34–10.12; P = .000) than in normal/underweight pregnant women (odds ratio 2.95; 95% confidence interval 1.74–4.26; P = .007). Weight and PlGF levels in study women had a significant negative correlation (r = 0.663; P = .002). Serum PlGF in early second trimester could be an effective predictor of early onset preeclampsia in overweight/obese pregnant women and may be more effective than in normal/underweight pregnant women.     

Neurocognitive impairment in obstructive sleep apnea

Obstructive sleep apnea syndrome (OSAS) is a common disorder with far-reaching health implications. One of the major consequences of OSAS is an impact on neurocognitive functioning. Several studies have shown that OSAS has an adverse effect on inductive and deductive reasoning, attention, vigilance, learning, and memory. Neurocognitive impairment can be measured objectively with tests such as the Wechsler Adult Intelligence Scale-Revised, the Psychomotor Vigilance Task, the Steer Clear Performance Test, and tests of repetitive finger tapping. In children, OSAS may cause attention-deficit hyperactivity disorder in addition to behavioral problems and learning disabilities. Risk factors for cognitive impairment include increasing age, male sex, apolipoprotein E ε4 allele positivity, current cigarette smoking, obesity, hypertension, diabetes mellitus, metabolic syndrome, Down syndrome, hypothyroidism, significant alcohol consumption, stroke, and the use of psychoactive medications. At a cellular level, OSAS likely causes cognitive impairment through intermittent hypoxia, hormonal imbalance, and/or systemic inflammation, either independently or via the resultant endothelial dysfunction that occurs. Excessive daytime sleepiness should be measured and minimized in all studies of neurocognitive impairment. Recent studies have used functional and structural neuroimaging to delineate the brain areas affected in patients with OSAS with neurocognitive dysfunction. A common finding in several of these studies is decreased hippocampal volume. Other affected brain areas include the frontal and parietal lobes of the brain, which show focal reductions in gray matter. These changes can be reversed at least partially with the use of CPAP, which highlights the importance of early recognition and treatment of OSAS. The currently available data in this field are quite limited, and more research is needed.     

Predictors of prolonged survival after allogeneic hematopoietic stem cell transplantation for multiple myeloma

A total of 149 patients with multiple myeloma (MM) who received allogeneic hematopoietic stem cell transplantation (allo-HCT) with myeloablative (MAC; n = 38) or reduced-intensity conditioning (RIC; n = 110) regimens at MD Anderson Cancer Center were evaluated. Of the total, 120 (81%) patients had relapsed or had refractory disease. Median age of MM patients was 50 (28-70) years with a followup time of 28.5 (3-164) months. The 100-day and 5-year treatment related mortality (TRM) rates were 17% and 47%, respectively. TRM was significantly lower with RIC regimens (13%) vs. 29% for MAC at 100 days (P = 0.012). The cumulative incidence of Grade II-IV acute graft-versus-host disease (GVHD) was 35% and chronic GVHD was 46%. PFS and OS at 5 years were 15% and 21%, respectively. In multivariate analysis, allo-HCT for primary remission consolidation was associated with longer PFS (HR 0.35; 95% CI, 0.18-0.67) and OS (HR 0.29; 95% CI 0.15-0.55), while absence of high-risk cytogenetics was associated with longer PFS only (HR 0.59; 95% CI 0.37-0.95). We observe that TRM has decreased with the use of RIC regimens, and long-term disease control can be expected in a subset of MM patients undergoing allo-HCT. Further studies should be conducted in carefully designed clinical trials in this patient population.     

Effect of tamoxifen on the enzymatic activity of human cytochrome CYP2B6

Tamoxifen is primarily used in the treatment of breast cancer. It has been approved as a chemopreventive agent for individuals at high risk for this disease. Tamoxifen is metabolized to a number of different products by cytochrome P450 enzymes. The effect of tamoxifen on the enzymatic activity of bacterially expressed human cytochrome CYP2B6 in a reconstituted system has been investigated. The 7-ethoxy-4-(trifluoromethyl)coumarin O-deethylation activity of purified CYP2B6 was inactivated by tamoxifen in a time- and concentration-dependent manner. Enzymatic activity was lost only in samples that were incubated with both tamoxifen and NADPH. The inactivation was characterized by a K(I) of 0.9 microM, a k(inact) of 0.02 min(-1), and a t(1/2) of 34 min. The loss in the 7-ethoxy-4-(trifluoromethyl)coumarin O-deethylation activity did not result in a similar percentage loss in the reduced carbon monoxide spectrum, suggesting that the heme moiety was not the major site of modification. The activity of CYP2B6 was not recovered after removal of free tamoxifen using spin column gel filtration. The loss in activity seemed to be due to a modification of the CYP2B6 and not reductase because adding fresh reductase back to the inactivated samples did not restore enzymatic activity. A reconstituted system containing purified CYP2B6, NADPH-reductase, and NADPH-generating system was found to catalyze tamoxifen metabolism to 4-OH-tamoxifen, 4'-OH-tamoxifen, and N-desmethyl-tamoxifen as analyzed by high-performance liquid chromatography analysis. Preliminary studies showed that tamoxifen had no effect on the activities of CYP1B1 and CYP3A4, whereas CYP2D6 and CYP2C9 exhibited a 25% loss in enzymatic activity.     

Growth patterns and anaemia status of HIV‐infected children living in an institutional facility in India

Objective  To understand the health status of HIV orphans in a well‐structured institutional facility in India. Method  Prospective longitudinal analysis of growth and anaemia prevalence among these children, between June 2008 and May 2011. Results  A total of 85 HIV‐infected orphan children residing at Sneha Care Home, Bangalore, for at least 1 year, were included in the analysis. Prevalence of anaemia at entry into the home was 40%, with the cumulative incidence of anaemia during the study period being 85%. At baseline, 79% were underweight and 72% were stunted. All children, irrespective of their antiretroviral therapy (ART) status, showed an improvement in nutritional status over time as demonstrated by a significant increase in weight (median weight‐for‐age Z‐score: ?2.75 to ?1.74, P < 0.001) and height Z‐scores (median height‐for‐age Z‐score: ?2.69 to ?1.63, P < 0.001). Conclusion  These findings suggest that good nutrition even in the absence of ART can bring about improvement in growth. The Sneha Care Home model indicates that the holistic approach used in the Home may have been helpful in combating HIV and poor nutritional status in severely malnourished orphaned children.     

Recruitment of medial prefrontal cortex neurons during alcohol withdrawal predicts cognitive impairment and excessive alcohol drinking

Chronic intermittent access to alcohol leads to the escalation of alcohol intake, similar to binge drinking in humans. Converging lines of evidence suggest that impairment of medial prefrontal cortex (mPFC) cognitive function and overactivation of the central nucleus of the amygdala (CeA) are key factors that lead to excessive drinking in dependence. However, the role of the mPFC and CeA in the escalation of alcohol intake in rats with a history of binge drinking without dependence is currently unknown. To address this issue, we examined FBJ murine osteosarcoma viral oncogene homolog (Fos) expression in the mPFC, CeA, hippocampus, and nucleus accumbens and evaluated working memory and anxiety-like behavior in rats given continuous (24 h/d for 7 d/wk) or intermittent (3 d/wk) access to alcohol (20% vol/vol) using a two-bottle choice paradigm. The results showed that abstinence from alcohol in rats with a history of escalation of alcohol intake specifically recruited GABA and corticotropin-releasing factor (CRF) neurons in the mPFC and produced working memory impairments associated with excessive alcohol drinking during acute (24–72 h) but not protracted (16 –68 d) abstinence. Moreover, abstinence from alcohol was associated with a functional disconnection of the mPFC and CeA but not mPFC and nucleus accumbens. These results show that recruitment of a subset of GABA and CRF neurons in the mPFC during withdrawal and disconnection of the PFC–CeA pathway may be critical for impaired executive control over motivated behavior, suggesting that dysregulation of mPFC interneurons may be an early index of neuroadaptation in alcohol dependence.     

Post‐transplantation cyclophosphamide versus conventional graft‐versus‐host disease prophylaxis in mismatched unrelated donor haematopoietic cell transplantation

Post‐transplantation cyclophosphamide (PTCy) is an effective strategy to prevent graft‐versus‐host disease (GVHD) after haploidentical haematopoietic cell transplantation (HCT). We determined the efficacy of PTCy‐based GVHD prophylaxis in human leucocyte antigen (HLA)‐mismatched unrelated donor (MMUD) HCT. We analysed 113 adult patients with high‐risk haematological malignancies who underwent one‐antigen MMUD transplantation between 2009 and 2013. Of these, 41 patients received PTCy, tacrolimus and mycophenolate mofetil (MMF) for GVHD prophylaxis; 72 patients received conventional prophylaxis with anti‐thymocyte globulin, tacrolimus and methotrexate. Graft source was primarily bone marrow (83% PTCy vs. 63% conventional group). Incidence of grade II–IV (37% vs. 36%, P = 0·8) and grade III–IV (17% vs. 12%, P = 0·5) acute GVHD was similar at day 100. However, the incidence of grade II‐IV acute GVHD by day 30 was significantly lower in the PTCy group (0% vs. 15%, P = 0·01). Median time to neutrophil (18 days vs. 12 days, P < 0·001) and platelet (25·5 days vs. 18 days, P = 0·05) engraftment was prolonged in PTCy group. Rates of graft failure, chronic GVHD, 2‐year non‐relapse mortality, relapse, progression‐free survival or overall survival were similar. Our results demonstrate that PTCy, tacrolimus and MMF for GVHD prophylaxis is safe and produced similar results as conventional prophylaxis in patients with one antigen HLA‐MMUD HCT.