Cochrane review on 'Statins for the treatment of dementia'

OBJECTIVES: This review aimed to assess the clinical efficacy and tolerability of statins in the treatment of dementia. METHODS: We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group, The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS, as well as many trials registries and grey literature sources (27 October 2008). Double-blind, randomized controlled trials of statins given for at least 6?months in people with a diagnosis of dementia were included. Two independent authors extracted and assessed data independently against the inclusion criteria. Data were pooled where appropriate and entered into a meta-analysis. RESULTS: Three studies were identified (748 participants, age range 50-90?years). All patients had a diagnosis of probable or possible Alzheimer's disease according to standard criteria, and most patients were established on a cholinesterase inhibitor. Change in Alzheimer's Disease Assessment Scale cognitive subscale from baseline was a primary outcome in three studies; when data were pooled, statins did not provide any beneficial effect in this cognitive measure (mean difference -1.12; 95% confidence interval -3.99, 1.75; p?=?0.44). All studies provided a change in Mini-Mental State Examination from baseline; there was no significant benefit from statins in this cognitive measure when the data were pooled (mean difference -1.53; 95% confidence interval -3.28; 0.21, p?=?0.08). There were no studies identified assessing the role of statins in treatment of vascular dementia. There was no evidence that statins were detrimental to cognition. CONCLUSIONS: There is insufficient evidence to recommend statins for the treatment of dementia. Copyright © 2012 John Wiley & Sons, Ltd.

Baseline Soil Variation Is a Major Factor in Arsenic Accumulation in Bengal Delta Paddy Rice

Factors responsible for paddy soil arsenic accumulation in the tubewell irrigated systems of the Bengal Delta were investigated. Baseline (i.e., nonirrigated) and paddy soils were collected from 30 field systems across Bangladesh. For each field, soil sampled at dry season (Boro) harvest i.e., the crop cycle irrigated with tubewell water, was collected along a 90 m transect away from the tubewell irrigation source. Baseline soil arsenic levels ranged from 0.8 to 21. mg/kg, with lower values found on the Pliestocene Terrace around Gazipur (average, 1.6 +/- 0.2 mg/kg), and higher levels found in Holecene sediment tracts of Jessore and Faridpur (average, 6.6 +/- 1.0 mg/kg). Two independent approaches were used to assess the extent of arsenic build-up in irrigated paddy soils. First, arsenic build-up in paddy soil at the end of dry season production (irrigated - baseline soil arsenic) was regressed against number of years irrigated and tubewell arsenic concentration. Years of irrigation was not significant (P 0.711), indicating no year-on-year arsenic build-up, whereas tubewell As concentration was significant (P = 0.008). The second approach was analysis of irrigated soils for 20 fields over 2 successive years. For nine of the fields there was a significant (P <0.05) decrease in soil arsenic from year 1 to 2, one field had a significant increase, whereas there was no change for the remaining 10. Over the dry season irrigation cycle, soil arsenic built-up in soils at a rate dependent on irrigation tubewell water, 35* (tubewell water concentration in mg/kg, mg/L). Grain arsenic rises steeply at low soil/shoot arsenic levels, plateauing out at concentratations. Baseline soil arsenic at Faridpur sites corresponded to grain arsenic levels at the start of this saturation phase. Therefore, variation in baseline levels of soil arsenic leads to a large range in grain arsenic. Where sites have high baseline soil arsenic, further additional arsenic from irrigation water only leads to a gradual increase in grain arsenic concentration.

Anthropometric measurements from a cross-sectional survey of community dwelling subjects aged over 90 years of age

To measure anthropometric variables of weight, height, body mass index (BMI) and triceps skin fold thickness (TSF) and produce local percentiles for > 90 y old subjects. To assess prevalence of conventional measures of under nutrition (BMI at or below 18.5 kg/m2) or over nutrition (BMI values > 30 kg/m2) in this age group.

Simple intervention method to reduce fumonisin exposure in a subsistence maize-farming community in South Africa

In the Centane magisterial area of South Africa, high rates of oesophageal cancer have been associated with home-grown maize contaminated with fumonisins. The aim of this study was to implement a simple intervention method to reduce fumonisin exposure in a subsistence-farming community. The hand-sorting and washing procedures, based on traditional maize-based food preparation practices, were previously customised under laboratory-controlled conditions. Home-grown maize and maize-based porridge collected at baseline were analysed for fumonisin B1, B2 and B3. The geometric mean (95% confidence interval) of fumonisin contamination in the home-grown maize at baseline was 1.67 (1.21-2.32) mg kg-1 and 1.24 (0.75-2.04) mg kg -1 (dry weight) in the porridge. Fumonisin exposure was based on individual stiff porridge consumption and the specific fumonisin levels in the porridge (dry weight) consumed. Porridge (dry weight) consumption at baseline was 0.34 kg day-1 and fumonisin exposure was 6.73 (3.90-11.6) mu g kg-1 body weight day-1. Female participants (n = 22) were trained to recognise and remove visibly infected/damaged kernels and to wash the remaining maize kernels. The discarded kernels represented 3.9% by weight and the fumonisins varied from 17.1 to 76.9 mg kg-1. The customised hand-sorting and washing procedures reduced fumonisin contamination in the maize and porridge by 84 and 65%, respectively. The intervention reduced fumonisin exposure by 62% to 2.55 (1.94-3.35) mu g kg-1 body weight day-1. This simple intervention method has the potential to improve food safety and health in subsistence-farming communities consuming fumonisin-contaminated maize as their staple diet.

Mitomycin-C supplemented trabeculectomy, phacoemulsification, and foldable lens implantation

Purpose: To evaluate the outcome of combined mitomycin-C filtering surgery, phacoemulsification, and foldable intraocular lens (IOL) implantation. Setting: Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. Methods: This retrospective study evaluated 182 eyes of 174 patients who had combined mitomycin-C trabeculectomy, phacoemulsification, and insertion of a foldable IOL through a 3.5 mm incision. Success of the combined procedure was defined as intraocular pressure (IOP) below 21 mm Hg, with or without medications, and no serious complication. Success rates were calculated using the Kaplan-Meier actuarial method. Results: Mean follow-up was 16.7 months ± 5.4 (SD). The probability of success at 6, 12, 18, and 24 months was 98.3, 95.6, 90.6, and 88.0%, respectively. When compared with preoperativety, visual acuity improved one or more lines in 148 eyes (81.3%) and worsened one or more lines in 15 (8.2%); 111 eyes (61.0%) achieved visual acuity of 20/40 or better. The most frequent complication was posterior capsule opacification requiring capsulotomy, which occurred in 22 cases (12.0%). Conclusion: The 1 year and 2 year IOP control rate of combined mitomycin-C filtering procedures and phacoemulsification in glaucoma patients was high.

A 75-81 GHz, 14.3 dBm Peak Output Power, 21 dB Peak Gain, SiGe Power-Combining Amplifier Operating from a Single 3.3 V Supply

A compact differential 4-way power combiner with 2.3 dB loss and high common-mode rejection characteristic for use in mm-wave PAs is presented. A complete circuit comprised of a power splitter, two-stage cascode PA array, and a power combiner was implemented in SiGe technology. Measured small-signal gain of at least 17 dB was obtained from 74.5 GHz to 80.5 GHz with a peak 21 dB at 79 GHz. The prototype delivered 13.2 dBm P1dB and 14.3 dBm Psat when operated from a single 3.3 V supply at 75 GHz.

Fast-drying multi-laminate bioadhesive films for transdermal and topical drug delivery

No bioadhesive patch-based system is currently marketed. This is despite an extensive number of literature reports on such systems detailing their advantages over conventional pressure sensitive adhesive-based patches in wet environments and describing successful delivery of a diverse array of drug substances. This lack of proprietary bioadhesive patches is largely due to the fact that such systems are exclusively water-based, meaning drying is difficult. In this paper we describe, for the first time, a novel multiple lamination method for production of bioadhesive patches. In contrast to patches produced using a conventional casting approach, which took 48 hours to dry, bioadhesive films prepared using the novel multiple lamination method were dried in 15?min and were folded into formed patches in a further 10?min. Patches prepared by both methods had comparable physicochemical properties. The multiple lamination method allowed supersaturation of 5-aminolevulinic acid to be achieved in formed patch matrices. However, drug release studies were unable to show an advantage for supersaturation with this particular drug, due to its water high solubility. The multiple lamination method allowed greater than 90% of incorporated nicotine to remain within formed patches, in contrast to the 48% achieved for patches prepared using a conventional casting approach. The procedure described here could readily be adapted for automation by industry. Due to the reduced time, energy and ensuing finance now required, this could lead to bioadhesive patch-based drug delivery systems becoming commercially viable. This would, in turn, mean that pathological conditions occurring in wet or moist areas of the body could now be routinely treated by prolonged site-specific drug delivery, as mediated by a commercially produced bioadhesive patch.

Measurement of nasal patency in anesthetized and conscious dogs

Experiments were undertaken to characterize a noninvasive chronic, model of nasal congestion in which nasal patency is measured using acoustic rhinometry. Compound 48/80 was administered intranasally to elicit nasal congestion in five beagle dogs either by syringe (0.5 ml) in thiopental sodium-anesthetized animals or as a mist (0.25 ml) in the same animals in the conscious state. Effects of mast cell degranulation on nasal cavity volume as well as on minimal cross-sectional area (A(min)) and intranasal distance to A(min) (D(min)) were studied. Compound 48/80 caused a dose-related decrease in nasal cavity volume and A(min) together with a variable increase in D(min). Maximal responses were seen at 90-120 min. Compound 48/80 was less effective in producing nasal congestion in conscious animals, which also had significantly larger basal nasal cavity volumes. These results demonstrate the utility of using acoustic rhinometry to measure parameters of nasal patency in dogs and suggest that this model may prove useful in studies of the actions of decongestant drugs.

Health status and 6 years survival of 552 90+ Italian sib-ships recruited within the EU Project GEHA (GEnetics of Healthy Ageing).

In a scenario of increasing life expectancy worldwide, it is mandatory to identify the characteristics of a healthy aging phenotype, including survival predictors, and to disentangle those related to environment/lifestyle versus those related to familiarity/genetics. To this aim we comprehensively characterised a cohort of 1,160 Italian subjects of 90 years and over (90+, mean age 93 years; age range 90-106 years) followed for 6 years survival, belonging to 552 sib-ships (familiar longevity) recruited (2005-2008) within the EU-funded GEHA project in three Italian geographic areas (Northern, Central and Southern Italy) different for urban/rural and socio-economical characteristics. On the whole, the following factors emerged as significant predictors of survival after 90 years of age: absence of cognitive impairment and physical disability, high hand grip strength scores and body mass index (BMI) values, "excellent/good" self-reported health, high haemoglobin and total cholesterol levels and low creatinine levels. These parameters, excluding BMI values, were also significantly associated within sib-ships, suggesting a strong familial/genetic component. Geographical micro-heterogeneity of survival predictors emerged, such as functional and physical status being more important in Southern than in Central and Northern Italy. In conclusion, we identified modifiable survival predictors related to specific domains, whose role and importance vary according to the geographic area considered and which can help in interpreting the genetic results obtained by the GEHA project, whose major aim is the comprehensive evaluation of phenotypic and genetic data.

How to classify the Oldest Old according to Health Status: A study of 1160 subjects belonging to 552 90+ Italian sibships characterised by familial longevity recruited within the GeHA EU project

The health status of the oldest old, the fastest increasing population segment worldwide, progressively becomes more heterogeneous, and this peculiarity represents a major obstacle to their classification. We compared the effectiveness of four previously proposed criteria (Franceschi et al., 2000; Evert et al., 2003; Gondo et al., 2006; Andersen-Ranberg et al., 2001) in 1160 phenotypically fully characterized Italian siblings of 90 years of age and older (90+, mean age: 93 years; age range: 90–106 years) belonging to 552 sib-ships, recruited in Northern, Central and Southern Italy within the EU-funded project GEHA, followed for a six-year-survival. Main findings were: (i) ‘‘healthy’’ subjects varied within a large range, i.e. 5.2% (Gondo), 8.7% (Evert), 17.7% (Franceschi), and 28.5% (Andersen-Ranberg); (ii) Central Italy subjects showed better health than those from Northern and Southern Italy; (iii) mortality risk was correlated with health status independently of geographical areas; and (iv) 90+ males, although fewer in number, were healthier than females, but with no survival advantage. In conclusion, we identified a modified version of Andersen-Ranberg criteria, based on the concomitant assessment of two basic domains (cognitive, SMMSE; physical, ADL), called ‘‘Simple Model of Functional Status’’ (SMFS), as the most effective proxy to distinguish healthy from not-healthy subjects. This model showed that health status was correlated within sib-ships, suggesting a familial/genetic component.

Endothelial lineage differentiation from induced pluripotent stem cells is regulated by microRNA-21 and transforming growth factor beta2 (TGF-β2) pathways

Finding a suitable cell source for endothelial cells (ECs) for cardiovascular regeneration is a challenging issue for regenerative medicine. In the paper we describe a novel mechanism regulating induced pluripotent stem cells (iPSC) differentiation into ECs, with a particular focus on miRNAs and their targets. We first established a protocol using collagen IV and VEGF to drive the functional differentiation of iPSCs into ECs and compared the miRNA signature of differentiated and undifferentiated cells. Among the miRNAs overrepresented in differentiated cells, we focused on microRNA-21 (miR-21) and studied its role in iPSC differentiation. Overexpression of miR-21 in pre-differentiated iPSCs induced EC marker upregulation and in vitro and in vivo capillary formation; accordingly, inhibition of miR-21 produced the opposite effects. Importantly, miR-21 overexpression increased TGF-β2 mRNA and secreted protein level, consistent with the strong upregulation of TGF-β2 during iPSC differentiation. Indeed, treatment of iPSCs with TGFβ-2 induced EC marker expression and in vitro tube formation. Inhibition of SMAD3, a downstream effector of TGFβ-2, strongly decreased VE-cadherin expression. Furthermore, TGFβ-2 neutralization and knockdown inhibited miR-21-induced EC marker expression. Finally, we confirmed the PTEN/Akt pathway as a direct target of miR-21 and we showed that PTEN knockdown is required for miR-21 mediated endothelial differentiation. In conclusion, we elucidated a novel signaling pathway that promotes the differentiation of iPSC into functional ECs suitable for regenerative medicine applications.

Risk of Several Cancers is Higher in Urban Areas after Adjusting for Socioeconomic Status. Results from a Two-Country Population-Based Study of 18 Common Cancers

Some studies suggest that there are urban-rural variations in cancer incidence but whether these simply reflect urban-rural socioeconomic variation is unclear. We investigated whether there were urban-rural variations in the incidence of 18 cancers, after adjusting for socioeconomic status. Cancers diagnosed between 1995 and 2007 were extracted from the population-based National Cancer Registry Ireland and Northern Ireland Cancer Registry and categorised by urban-rural status, based on population density of area of residence at diagnosis (rural 15 people per hectare). Relative risks (RR) were calculated by negative binomial regression, adjusting for age, country and three area-based markers of socioeconomic status. Risks were significantly higher in both sexes in urban than rural residents with head and neck (males RR urban vs. rural = 1.53, 95 % CI 1.42-1.64; females RR = 1.29, 95 % CI 1.15-1.45), esophageal (males 1.21, 1.11-1.31; females 1.21, 1.08-1.35), stomach (males 1.36, 1.27-1.46; females 1.19, 1.08-1.30), colorectal (males 1.14, 1.09-1.18; females 1.04, 1.00-1.09), lung (males 1.54, 1.47-1.61; females 1.74, 1.65-1.84), non-melanoma skin (males 1.13, 1.10-1.17; females 1.23, 1.19-1.27) and bladder (males 1.30, 1.21-1.39; females 1.31, 1.17-1.46) cancers. Risks of breast, cervical, kidney and brain cancer were significantly higher in females in urban areas. Prostate cancer risk was higher in rural areas (0.94, 0.90-0.97). Other cancers showed no significant urban-rural differences. After adjusting for socioeconomic variation, urban-rural differences were evident for 12 of 18 cancers. Variations in healthcare utilization and known risk factors likely explain some of the observed associations. Explanations for others are unclear and, in the interests of equity, warrant further investigation. © 2014 The New York Academy of Medicine.

Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age

The genetic contribution to the variation in human lifespan is approximately 25%.  Despite the large number of identified disease-susceptibility loci, it is not known which loci influence population mortality.  We performed a genome-wide association meta-analysis of 7729 long-lived individuals of European descent (≥ 85 years) and 16121 younger controls (< 65 years) followed by replication in an additional set of 13060 long-lived individuals and 61156 controls. In addition, we performed a subset analysis in cases ≥ 90 years. We observed genome-wide significant association with longevity, as reflected by survival to ages beyond 90 years, at a novel locus, rs2149954, on chromosome 5q33.3 (OR = 1.10, P =1.74 x 10-8). We also confirmed association of rs4420638 on chromosome 19q13.32 (OR = 0.72, P = 3.40 x 10-36), representing the TOMM40/APOE/APOC1 locus. In a prospective meta-analysis (n = 34103) the minor allele of rs2149954 (T) on chromosome 5q33.3 associates with increased survival (HR = 0.95, P = 0.003). This allele has previously been reported to associate with low blood pressure in middle age. Interestingly, the minor allele (T) associates with decreased cardiovascular mortality risk, independent of blood pressure. We report on the first GWAS-identified longevity locus on chromosome 5q33.3 influencing survival in the general European population. The minor allele of this locus associates with low blood pressure in middle age, although the contribution of this allele to survival may be less dependent on blood pressure. Hence, the pleiotropic mechanisms by which this intragenic variation contributes to lifespan regulation have to be elucidated.

Antioxidant Activity of Sesame (Seasamum indicum L.) Cake Extract for the Stabilization of Olein Based Butter

This study investigated the effect of ethanolic sesame cake extract on oxidative stabilization of olein based butter. Fractionation of cream was performed by the dry fractionation technique at 10 °C, ethanolic sesame cake extract (SCE) was incorporated into olein butter at three different concentrations; 50, 100, 150 ppm (T1, T2, T3) and compared with a control. The total phenolic content of SCE was 1.72 (mg gallic acid equivalent g−1 dry weight). The HPLC characterization of ethanolic sesame cake revealed the presence of antioxidant substances viz. sesamol, sesamin and sesamolin in higher extents. The DPPH free radical scavenging activity of SCE was 83 % as compared to 64 and 75 % in BHA and BHT. Fractionation of milk fat at 10 °C significantly (p < 0.05) influenced the fatty acid profile of olein and stearin fractions from the parent milk fat. Concentration of oleic acid and linoleic acid in olein fraction was 29.62 and 33.46 % greater than the parent milk fat. The loss of C18:1 in 90 days stored control and T3 was 24.37 and 3.58 %, respectively, 58 % C18:2 was broken down into oxidation products over 8.55 % loss in T3. The peroxide value of control, T1, T2, BHT and T3 in the Schaal oven test was 8.59, 8.12, 5.34, 4.52 and 2.49 (mequiv O2/kg). The peroxide value and anisidine value of 3 months stored control and T3 were 1.21, 0.42 (mequiv O2/kg) and 27.25, 13.25, respectively. The concentration of conjugated dienes in T3 was substantially less than the control. The induction period of T3 was considerably higher than BHT with no difference in sensory characteristics (p > 0.05). Ethanolic SCE can be used for the long-term preservation of olein butter, with acceptable sensory characteristics.