Nicotine exposure during adolescence: cognitive performance and brain gene expression in adult heterozygous reeler mice

Rationale

We have recently reported nicotine-induced stimulation of reelin and glutamic acid decarboxylase 67 (GAD67) mRNA expression levels in the brain of heterozygous reeler mice (HRM), a putative animal model for the study of symptoms relevant to major behavioral disorders.

Objectives

We aimed to evaluate long-term behavioral effects and brain molecular changes as a result of adaptations to nicotine exposure in the developing HRM males.

Methods

Adolescent mice (pnd 37–42) were exposed to oral nicotine (10 mg/l) in a 6-day free-choice drinking schedule. As expected, no differences in total nicotine intake between WT (wild-type) mice and HRM were found.

Results

Long-term behavioral effects and brain molecular changes, as a consequence of nicotine exposure during adolescence, were only evidenced in HRM. Indeed, HRM perseverative exploratory behavior and poor cognitive performance were modulated to WT levels by subchronic exposure to nicotine during development. Furthermore, the expected reduction in the expression of mRNA of reelin and GAD67 in behaviorally relevant brain areas of HRM appeared persistently restored by nicotine. For brain-derived neurotrophic factor (BDNF) mRNA expression, no genotype-dependent changes appeared. However, expression levels were increased by previous nicotine in brains from both genotypes. The mRNA encoding for nicotine receptor subunits (α7, β2 and α4) did not differ between genotypes and as a result of previous nicotine exposure.

Conclusion

These findings support the hypothesis of pre-existing vulnerability (based on haploinsufficiency of reelin) to brain and behavioral disorders and regulative short- and long-term effects associated with nicotine modulation.     

Influence of the Type of Cement on the Action of the Admixture Containing Aluminum Powder

The study of the effect of cement type on the action of an admixture increasing the volume of concrete (containing aluminum powder), used in amounts of 0.5–1.5% of cement mass, was presented. The tests were carried out on cement mortars with Portland (CEM I) and ground granulated blast-furnace slag cement (CEM III). The following tests were carried out for the tested mortars: the air content in fresh mortars, compressive strength, flexural strength, increase in mortar volume, bulk density, pore structure evaluation (by the computer image analysis method) and changes in the concentration of OH⁻ ions during the hydration of used cements. Differences in the action of the tested admixture depending on the cement used were found. To induce the expansion of CEM III mortars, a smaller amount of admixture is required than in the case of CEM I cement. Using the admixture in amounts above 1% of the cement mass causes cracks of mortars with CEM III cement due to slow hydrogen evolution, which occurs after mortar plasticity is lost. The use of an aluminum-containing admixture reduces the strength properties of the cement mortars, the effect being stronger in the case of CEM III cement. The influence of the sample molding time on the admixture action was also found.     

Extended-release naltrexone/bupropion and liver health: Pooled,post hoc analysis from four randomized controlled trials

Sustained weight loss improves liver histology in non-alcoholic fatty liver disease. This post hoc analysis of four phase III, 56-week, randomized controlled trials investigated if extended-release naltrexone and bupropion (NB) affects alanine aminotransferase (ALT) and Fibrosis-4 (FIB-4) index in adults with overweight or obesity. Two thousand and seventy-three subjects (NB = 1310; placebo = 763; 79.0% female; 81.6% Caucasian) had baseline mean weight 101 kg, body mass index 36.2 kg/m², ALT 26.9 IU/L and FIB-4 0.79. At 56 weeks, NB-treated subjects experienced more weight loss than placebo (8.7 vs. 3.2 kg, respectively, P < .0001). Weight loss, independent of treatment, was associated with improved ALT and FIB-4 (P < .0001). There was a significant independent effect of NB on change from baseline for FIB-4 (P < .0001), but not for ALT (P = .54). Categorical ALT response (from above to within normal ranges: 10-40 IU/L for men; 7-35 IU/L for women) and achievement of 25% and 50% reduction in ALT were greater for NB versus placebo, and independently affected by weight loss (P < .0001), but not treatment. NB-associated weight loss may improve liver health by normalizing ALT values for those with high baseline levels.     

From microbiota toward gastro-enteropancreatic neuroendocrine neoplasms: Are we on the highway to hell?

Gut microbiota is represented by different microorganisms that colonize the intestinal tract, mostly the large intestine, such as bacteria, fungi, archaea and viruses. The gut microbial balance has a key role in several functions. It modulates the host’s metabolism, maintains the gut barrier integrity, participates in the xenobiotics and drug metabolism, and acts as protection against gastro-intestinal pathogens through the host’s immune system modulation. The impaired gut microbiota, called dysbiosis, may be the result of an imbalance in this equilibrium and is linked with different diseases, including cancer. While most of the studies have focused on the association between microbiota and gastrointestinal adenocarcinomas, very little is known about gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). In this review, we provide an overview concerning the complex interplay between gut microbiota and GEP NENs, focusing on the potential role in tumorigenesis and progression in these tumors.

     

Psychiatric nursing staffs’ attitudes towards the use of containment methods in psychiatric inpatient care: An integrative review

One of the international objectives in psychiatric care is reducing the use of coercion. Containment methods are meant to keep patients safe, yet usually include coercion. Nurses play a key role in deciding whether or not containment should be used and, as such, their attitudes towards containment can significantly impact the extent to which these methods are applied. The aim of this integrative review was to identify, analyse, and synthesize the available research on psychiatric nursing staffs’ attitudes towards containment methods in inpatient psychiatric care. An electronic search was conducted using the CINAHL, Scopus, and PsycINFO databases. In addition, the citations of identified studies were screened for relevant research. A total of 24 relevant papers published between 2002 and 2017 were selected for further analysis. These studies revealed variation in nursing staffs’ attitudes towards the use of containment methods. The use of containment methods seems to be widely accepted and nurses reported rarely considering alternative measures. It appears that attitudes towards containment have continuously become more negative, although the change has not been very pronounced. The concept of attitude was only defined in two studies. Thus, future research should strive to clarify this concept, as a generally accepted definition for attitude within nursing research and the utilization of all dimensions of this concept are both essential to the nursing field. Currently, it would be important to focus on changing attitudes among psychiatric nursing staff to reduce the use of containment methods; this calls for more research on nursing staffs’ attitudes.     

Three novel mutations in CYP21 gene in Brazilian patients with the classical form of 21-hydroxylase deficiency due to a founder effect

Three different new mutations were found after CYP21 gene sequencing in three unrelated patients with the classical form of the 21-hydroxylase deficiency. These mutations were also screened in their affected relatives. In one patient and her brother, both affected with the simple virilizing form and in their aunt, with the nonclassical form, an AG>GG transition was found in the acceptor site of intron 2. In another patient with the salt wasting form, we found a 1003 1004 insA, in exon 4, that altered the reading frame and created a stop codon in codon 297. In the third patient and his sister, we found a C>T transition in codon 408. This transition led to the substitution of arginine by cysteine (R408C) in a conserved region where arginine is conserved in at least four different species. These siblings with the R408C mutation, both affected with the salt wasting form, have the IVS2-13A/C>G mutation in the other allele, suggesting that the R408C should lead to complete impairment of enzymatic activity. To rule out the possibility of polymorphism, R408C was screened through allele specific PCR, and it was not found in 100 normal alleles. The screening of these three new mutations by allele-specific PCR or enzymatic restriction in 212 CAH patients disclosed their presence in 2.3% (9/387) of the alleles. All three new mutations were found in compound heterozygous state with previously known mutations. Microsatellite studies, using markers flanking CYP21 gene, revealed that each new mutation presents the same haplotype, suggesting a gene founder effect, similar to what was previously observed with the G424S mutation also described in our population. Although microconversion events are the main cause of mutations in the CYP21 gene, random mutations with a common origin can also be the cause of 21-hydroxylase deficiency.