Donepezil and related cholinesterase inhibitors as mood and behavioral controlling agents.

Acetylcholinesterase inhibitors (ChEIs) enhance neuronal transmission by increasing the availability of acetylcholine in muscarinic and nicotinic receptors. This effect is believed to be responsible for the beneficial and protective effects of ChEIs on cognition in patients with Alzheimer's disease (AD). Effects of ChEIs on mood and behavior have also been reported. Earlier observations were limited by the exclusive availability of intravenous forms of administration, the short half-life of the formulations, and the high frequency of peripheral side effects. The introduction, in recent years, of better tolerated and less invasive compounds has rekindled the interest in cholinergic central nervous system mechanisms and has given rise to studies in areas other than cognition. The ChEI donepezil has been involved in the largest number of studies and positive reports. Preliminary observations suggest the possible value of ChEIs in the management of behavioral dysregulation, apathy, irritability, psychosis, depression, mania, tics, and delirium and in the diagnosis of depression, panic, and personality disorders

To respond or not to respond - a personal perspective of intestinal tolerance

For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research

Reducing Alaska Native paediatric oral health disparities: a systematic review of oral health interventions and a case study on multilevel strategies to reduce sugar-sweetened beverage intake

Background. Tooth decay is the most common paediatric disease and there is a serious paediatric tooth decay epidemic in Alaska Native communities. When untreated, tooth decay can lead to pain, infection, systemic health problems, hospitalisations and in rare cases death, as well as school absenteeism, poor grades and low quality-of-life. The extent to which population-based oral health interventions have been conducted in Alaska Native paediatric populations is unknown. Objective. To conduct a systematic review of oral health interventions aimed at Alaska Native children below age 18 and to present a case study and conceptual model on multilevel intervention strategies aimed at reducing sugar-sweetened beverage (SSB) intake among Alaska Native children. Design. Based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Statement, the terms “Alaska Native”, “children” and “oral health” were used to search Medline, Embase, Web of Science, GoogleScholar and health foundation websites (1970–2012) for relevant clinical trials and evaluation studies. Results. Eighty-five studies were found in Medline, Embase and Web of Science databases and there were 663 hits in GoogleScholar. A total of 9 publications were included in the qualitative review. These publications describe 3 interventions that focused on: reducing paediatric tooth decay by educating families and communities; providing dental chemotherapeutics to pregnant women; and training mid-level dental care providers. While these approaches have the potential to improve the oral health of Alaska Native children, there are unique challenges regarding intervention acceptability, reach and sustainability. A case study and conceptual model are presented on multilevel strategies to reduce SSB intake among Alaska Native children. Conclusions. Few oral health interventions have been tested within Alaska Native communities. Community-centred multilevel interventions are promising approaches to improve the oral and systemic health of Alaska Native children. Future investigators should evaluate the feasibility of implementing multilevel interventions and policies within Alaska Native communities as a way to reduce children's health disparities

NucTools: analysis of chromatin feature occupancy profiles from high-throughput sequencing data

Background: Biomedical applications of high-throughput sequencing methods generate a vast amount of data in which numerous chromatin features are mapped along the genome. The results are frequently analysed by creating binary data sets that link the presence/absence of a given feature to specific genomic loci. However, the nucleosome occupancy or chromatin accessibility landscape is essentially continuous. It is currently a challenge in the field to cope with continuous distributions of deep sequencing chromatin readouts and to integrate the different types of discrete chromatin features to reveal linkages between them. Results: Here we introduce the NucTools suite of Perl scripts as well as MATLAB- and R-based visualization programs for a nucleosome-centred downstream analysis of deep sequencing data. NucTools accounts for the continuous distribution of nucleosome occupancy. It allows calculations of nucleosome occupancy profiles averaged over several replicates, comparisons of nucleosome occupancy landscapes between different experimental conditions, and the estimation of the changes of integral chromatin properties such as the nucleosome repeat length. Furthermore, NucTools facilitates the annotation of nucleosome occupancy with other chromatin features like binding of transcription factors or architectural proteins, and epigenetic marks like histone modifications or DNA methylation. The applications of NucTools are demonstrated for the comparison of several datasets for nucleosome occupancy in mouse embryonic stem cells (ESCs) and mouse embryonic fibroblasts (MEFs). Conclusions: The typical workflows of data processing and integrative analysis with NucTools reveal information on the interplay of nucleosome positioning with other features such as for example binding of a transcription factor CTCF, regions with stable and unstable nucleosomes, and domains of large organized chromatin K9me2 modifications (LOCKs). As potential limitations and problems we discuss how inter-replicate variability of MNase-seq experiments can be addressed

Biomineralisation by earthworms: an investigation into the stability and distribution of amorphous calcium carbonate

Background Many biominerals form from amorphous calcium carbonate (ACC), but this phase is highly unstable when synthesised in its pure form inorganically. Several species of earthworm secrete calcium carbonate granules which contain highly stable ACC. We analysed the milky fluid from which granules form and solid granules for amino acid (by liquid chromatography) and functional group (by Fourier transform infrared (FTIR) spectroscopy) compositions. Granule elemental composition was determined using inductively coupled plasma-optical emission spectroscopy (ICP-OES) and electron microprobe analysis (EMPA). Mass of ACC present in solid granules was quantified using FTIR and compared to granule elemental and amino acid compositions. Bulk analysis of granules was of powdered bulk material. Spatially resolved analysis was of thin sections of granules using synchrotron-based μ-FTIR and EMPA electron microprobe analysis. Results The milky fluid from which granules form is amino acid-rich (≤ 136 ± 3 nmol mg−1 (n = 3; ± std dev) per individual amino acid); the CaCO3 phase present is ACC. Even four years after production, granules contain ACC. No correlation exists between mass of ACC present and granule elemental composition. Granule amino acid concentrations correlate well with ACC content (r ≥ 0.7, p ≤ 0.05) consistent with a role for amino acids (or the proteins they make up) in ACC stabilisation. Intra-granule variation in ACC (RSD = 16%) and amino acid concentration (RSD = 22–35%) was high for granules produced by the same earthworm. Maps of ACC distribution produced using synchrotron-based μ-FTIR mapping of granule thin sections and the relative intensity of the ν2: ν4 peak ratio, cluster analysis and component regression using ACC and calcite standards showed similar spatial distributions of likely ACC-rich and calcite-rich areas. We could not identify organic peaks in the μ-FTIR spectra and thus could not determine whether ACC-rich domains also had relatively high amino acid concentrations. No correlation exists between ACC distribution and elemental concentrations determined by EMPA. Conclusions ACC present in earthworm CaCO3 granules is highly stable. Our results suggest a role for amino acids (or proteins) in this stability. We see no evidence for stabilisation of ACC by incorporation of inorganic components

Chronic kidney disease in the type 2 diabetic patients: prevalence and associated variables in a random sample of 2642 patients of a Mediterranean area

Background: Kidney disease is associated with an increased total mortality and cardiovascular morbimortality in the general population and in patients with Type 2 diabetes. The aim of this study is to determine the prevalence of kidney disease and different types of renal disease in patients with type 2 diabetes (T2DM). Methods: Cross-sectional study in a random sample of 2,642 T2DM patients cared for in primary care during 2007. Studied variables: demographic and clinical characteristics, pharmacological treatments and T2DM complications (diabetic foot, retinopathy, coronary heart disease and stroke). Variables of renal function were defined as follows: 1) Microalbuminuria: albumin excretion rate & 30 mg/g or 3.5 mg/mmol, 2) Macroalbuminuria: albumin excretion rate & 300 mg/g or 35 mg/mmol, 3) Kidney disease (KD): glomerular filtration rate according to Modification of Diet in Renal Disease < 60 ml/min/1.73 m2 and/or the presence of albuminuria, 4) Renal impairment (RI): glomerular filtration rate < 60 ml/min/1.73 m2, 5) Nonalbuminuric RI: glomerular filtration rate < 60 ml/min/1.73 m2 without albuminuria and, 5) Diabetic nephropathy (DN): macroalbuminuria or microalbuminuria plus diabetic retinopathy. Results: The prevalence of different types of renal disease in patients was: 34.1% KD, 22.9% RI, 19.5% albuminuria and 16.4% diabetic nephropathy (DN). The prevalence of albuminuria without RI (13.5%) and nonalbuminuric RI (14.7%) was similar. After adjusting per age, BMI, cholesterol, blood pressure and macrovascular disease, RI was significantly associated with the female gender (OR 2.20; CI 95% 1.86-2.59), microvascular disease (OR 2.14; CI 95% 1.8-2.54) and insulin treatment (OR 1.82; CI 95% 1.39-2.38), and inversely associated with HbA1c (OR 0.85 for every 1% increase; CI 95% 0.80-0.91). Albuminuria without RI was inversely associated with the female gender (OR 0.27; CI 95% 0.21-0.35), duration of diabetes (OR 0.94 per year; CI 95% 0.91-0.97) and directly associated with HbA1c (OR 1.19 for every 1% increase; CI 95% 1.09-1.3). Conclusions: One-third of the sample population in this study has KD. The presence or absence of albuminuria identifies two subgroups with different characteristics related to gender, the duration of diabetes and metabolic status of the patient. It is important to determine both albuminuria and GFR estimation to diagnose KD

How Much Does Effortful Thinking Underlie Observers’ Reactions to Victimization?

From blaming to helping innocent victims, just-world research has revealed that observers react to victimization in a variety of ways. Recent research suggests that such responses to victimization require effortful thought, whereas other research has shown that people can react to these situations intuitively. Along with manipulating just-world threat, across seven experiments, we manipulated or measured participants’ level of mental processing before assessing judgments of victim derogation, blame, willingness to help, and ultimate justice reasoning. The effect of just-world threat on these responses held constant over a range of manipulations/measures, suggesting that the processes involved in maintaining a belief in a just world are not restricted to the rational, deliberative level of mental processing but also occur intuitively

Parasites and immunotherapy: with or against?

Immunotherapy is a sort of therapy in which antibody or antigen administrates to the patient in order to treat or reduce the severity of complications of disease. This kind of treatment practiced in a wide variety of diseases including infectious diseases, autoimmune disorders, cancers and allergy. Successful and unsuccessful immunotherapeutic strategies have been practiced in variety of parasitic infections. On the other hand parasites or parasite antigens have also been considered for immunotherapy against other diseases such as cancer, asthma and multiple sclerosis. In this paper immunotherapy against common parasitic infections, and also immunotherapy of cancer, asthma and multiple sclerosis with parasites or parasite antigens have been reviewe

Parental attributions of control for child behaviour and their relation to discipline practices in parents of children with and without developmental delays

Children with developmental delays (DD) are at risk for developing behavior problems. Research suggests that parents’ causal attributions for child behavior are related to parenting. This study investigated this association in parents of children with DD compared to parents of typically developing (TD) children. It specifically focused on attributions of child control by separating these from attributions of responsibility, blame and intent, and from attributions of parent control and responsibility. Fifty-one parents of children with DD and 69 parents of TD children completed two questionnaires. The Written Analogue Questionnaire measured causal attributions. The Parenting Scale measured dysfunctional discipline practices. Parents of children with DD viewed the child’s role in problematic behavior more positively while also viewing misbehavior as more fixed than parents of TD children. Parents of TD children who viewed their child as more in control over misbehavior used less dysfunctional discipline, but this association was not found for parents of children with DD. The results advance understanding of how parents perceive behavior problems in children with DD and the important role these perceptions play in parental behavior management strategies. More importantly, these perceptions relate to discipline practices differently for parents of children with DD compared to parents of TD children, highlighting that parent interventions should be adapted to the specific needs of parents of children with DD