Pharmacological Stimulation of the Brain Serotonin Receptor 7 as a Novel Therapeutic Approach for Rett Syndrome

Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioral and physiological symptoms. Mutations in the methyl CpG-binding protein 2 gene (MECP2) cause >95% of classic cases, and currently there is no cure for this devastating disorder. The serotonin receptor 7 (5-HT7R) is linked to neuro-physiological regulation of circadian rhythm, mood, cognition, and synaptic plasticity. We presently report that 5-HT7R density is consistently reduced in cortical and hippocampal brain areas of symptomatic MeCP2–308 male mice, a RTT model. Systemic repeated treatment with LP-211 (0.25 mg/kg once/day for 7 days), a brain-penetrant selective 5-HT7R agonist, was able to rescue RTT-related defective performance: anxiety-related profiles in a Light/Dark test, motor abilities in a Dowel test, the exploratory behavior in the Marble Burying test, as well as memory in the Novelty Preference task. In the brain of RTT mice, LP-211 also reversed the abnormal activation of PAK and cofilin (key regulators of actin cytoskeleton dynamics) and of the ribosomal protein (rp) S6, whose reduced activation in MECP2 mutant neurons by mTOR is responsible for the altered protein translational control. Present findings indicate that pharmacological targeting of 5-HT7R improves specific behavioral and molecular manifestations of RTT, thus representing a first step toward the validation of an innovative systemic treatment. Beyond RTT, the latter might be extended to other disorders associated with intellectual disability.     

The Effect of Cyanobacterial Biomass Enrichment by Centrifugation and GF/C Filtration on Subsequent Microcystin Measurement

Microcystins are cyclic peptides produced by multiple cyanobacterial genera. After accumulation in the liver of animals they inhibit eukaryotic serine/threonine protein phosphatases, causing liver disease or death. Accurate detection/quantification of microcystins is essential to ensure safe water resources and to enable research on this toxin. Previous methodological comparisons have focused on detection and extraction techniques, but have not investigated the commonly used biomass enrichment steps. These enrichment steps could modulate toxin production as recent studies have demonstrated that high cyanobacterial cell densities cause increased microcystin levels. In this study, three microcystin-producing strains were processed using no cell enrichment steps (by direct freezing at three temperatures) and with biomass enrichment (by centrifugation or GF/C filtration). After extraction, microcystins were analyzed using liquid chromatography-tandem mass spectrometry. All processing methods tested, except GF/C filtration, resulted in comparable microcystin quotas for all strains. The low yields observed for the filtration samples were caused by adsorption of arginine-containing microcystins to the GF/C filters. Whilst biomass enrichment did not affect microcystin metabolism over the time-frame of normal sample processing, problems associated with GF/C filtration were identified. The most widely applicable processing method was direct freezing of samples as it could be utilized in both field and laboratory environments.     

Psychiatric nursing care experiences of immigrant patients: A Focused ethnographic study

This study aimed to describe the psychiatric nursing care experiences of immigrant patients. The incidence of mental health problems is higher and the use of mental health services is lower among immigrants, especially refugees, compared with the majority of the population. The study uses a qualitative research approach, with an emphasis on focused ethnography research methods. The participants were immigrant patients (N = 14) residing in adult psychiatric wards of certain hospitals (N = 3) selected for the study. A majority of the participants were refugees or asylum seekers. A total of 21 in‐depth interviews were conducted. The experiences of these immigrant patients, both in their home countries and in their country of residence, had had an adverse effect on their mental health, with past traumatic experiences being the most central factor. Their symptoms included depression, anxiety, somatization, and psychosis. The findings show that the categories of factors that helped promote recovery among immigrant patients were nursing, medical treatment, care environment, and the patients' own methods. Based on the findings, a systematic evaluation of traumatic experiences is recommended for immigrants from countries with a history of war and/or political violence. Healthcare providers should also consider the importance of cultural desire in psychiatric nursing for the recovery of patients.     

Aminoacid Sequence of Dogfish M4 Lactate Dehydrogenase

About 80% of the aminoacid sequence of dogfish (Squalus acanthius) M(4) lactate dehydrogenase (EC 1.1.1.27) has been elucidated. Several sequence homologies with peptides from pig H(4) and pig M(4) lactate dehydrogenase are identified. Histidine 195 is homologous to the essential histidine residue in pig H(4) lactate dehydrogenase. Similarities in the sequence around the "essential" cysteine residue of lactate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, and yeast and liver alcohol dehydrogenase are delineated.     

Novel Betacoronavirus in Dromedaries of the Middle East, 2013

In 2013, a novel betacoronavirus was identified in fecal samples from dromedaries in Dubai, United Arab Emirates. Antibodies against the recombinant nucleocapsid protein of the virus, which we named dromedary camel coronavirus (DcCoV) UAE-HKU23, were detected in 52% of 59 dromedary serum samples tested. In an analysis of 3 complete DcCoV UAE-HKU23 genomes, we identified the virus as a betacoronavirus in lineage A1. The DcCoV UAE-HKU23 genome has G+C contents; a general preference for G/C in the third position of codons; a cleavage site for spike protein; and a membrane protein of similar length to that of other betacoronavirus A1 members, to which DcCoV UAE-HKU23 is phylogenetically closely related. Along with this coronavirus, viruses of at least 8 other families have been found to infect camels. Because camels have a close association with humans, continuous surveillance should be conducted to understand the potential for virus emergence in camels and for virus transmission to humans.     

New Hepatitis E Virus Genotype in Camels,the Middle East

In a molecular epidemiology study of hepatitis E virus (HEV) in dromedaries in Dubai, United Arab Emirates, HEV was detected in fecal samples from 3 camels. Complete genome sequencing of 2 strains showed >20% overall nucleotide difference to known HEVs. Comparative genomic and phylogenetic analyses revealed a previously unrecognized HEV genotype.Hepatitis E virus (HEV) belongs to the family Hepeviridae and genus Hepevirus. Among humans worldwide, HEV is the most common cause of acute viral hepatitis. The disease is generally self-limiting, but mortality rates are high among pregnant women and young infants. Chronic HEV infection is a problem for immunocompromised patients, such as those who have received a solid organ transplant and those with HIV infection. In addition to humans, HEV has been found in the other mammals: pigs, boar, deer, rodents, ferrets, rabbits, mongoose, bats, cattle, sheep, foxes, minks, and horses (1–3). Among the 4 known HEV genotypes, HEV1 and HEV2 infect only humans; whereas, HEV3 and HEV4 can infect humans, pigs, and other mammals. Human infections with HEV3 and HEV4 have been associated with consumption of raw or undercooked pork or game meat (4). Traditionally, HEV infection is mainly transmitted through water contaminated with infected feces. Since water supplies and sanitary infrastructures have been improved, animals have become a major source of human HEV infection. We detected HEV in fecal samples from dromedary camels in the Middle East.     

A safety,length of stay,and cost analysis of minimally invasive microsurgery for anterior circulation aneurysms

Objectives

The aim of our study was to evaluate minimally invasive techniques for the treatment of anterior circulation aneurysms versus standard surgery, and to calculate the impact of these techniques on health resources, length of stay, and treatment costs.

Methods

A consecutive series of 24 patients with ruptured and 30 with unruptured anterior circulation aneurysms treated with minimally invasive microsurgery (MIM) by the same surgeon was compared with a matched series of standard microsurgeries (SM) conducted for 23 ruptured and 22 unruptured aneurysms. Complication rates, aneurysm obliteration, modified Rankin Scale (mRS) outcomes, length of stay, and treatment costs were assessed.

Results

Surgical complications, aneurysm obliteration rates and mRS outcomes were comparable between MIM and SM groups in ruptured and unruptured aneurysm cohorts. MIM resulted in shorter operative times both in unruptured (102.7?±?4.35 vs 194.7?±?10.26 min, p?<?0.0001) and ruptured aneurysms (124.3?±?827 vs 209?±?13.84 min, p?<?0.0001). Length of stay was reduced in patients with MIM for unruptured aneurysms (1.55?±?24 vs 4.28?±?0.71 days, p?<?0.000,1) but not in those with ruptured aneurysms. MIM reduced treatment costs of unruptured aneurysm patients, mainly through reduced utilization of inpatient resources (non-acute bed costs in CAD: 371.2?±?80.99 vs 1440?±?224.1, p?<?0.0001), whereas costs were comparable in patients with ruptured aneurysms.

Conclusion

Minimally invasive surgery is a safe and effective approach for the treatment of ruptured and unruptured aneurysms of the anterior circulation. In patients with unruptured aneurysms, reduced invasiveness and shorter operative times decreased length of stay, which reflects improved patient postoperative recovery. Overall, this translated into bed resource economy and cost reduction.     

Low-Risk Diet and Lifestyle Habits in the Primary Prevention of Myocardial Infarction in Men : A Population-Based Prospective Cohort Study

Background

Adherence to a combination of healthy dietary and lifestyle practices may have an impressive impact on the primary prevention of myocardial infarction (MI).

Objectives

The aim of this study was to examine the benefit of combined low-risk diet and healthy lifestyle practices on the incidence of MI in men.

Methods

The population-based, prospective cohort of Swedish men comprised 45- to 79-year-old men who completed a detailed questionnaire on diet and lifestyle at baseline in 1997. In total, 20,721 men with no history of cancer, cardiovascular disease, diabetes, hypertension, or high cholesterol levels were followed through 2009. Low-risk behavior included 5 factors: a healthy diet (top quintile of Recommended Food Score), moderate alcohol consumption (10 to 30 g/day), no smoking, being physically active (walking/bicycling ≥40 min/day and exercising ≥1 h/week), and having no abdominal adiposity (waist circumference <95 cm).

Results

During 11 years of follow-up, we ascertained 1,361 incident cases of MI. The low-risk dietary choice together with moderate alcohol consumption was associated with a relative risk of 0.65 (95% confidence interval [CI]: 0.48 to 0.87) compared with men having 0 of 5 low-risk factors. Men having all 5 low-risk factors compared with those with 0 low-risk factors had a relative risk of 0.14 (95% CI: 0.04 to 0.43). This combination of healthy behaviors, present in 1% of the men, could prevent 79% (95% CI: 34% to 93%) of the MI events on the basis of the study population.

Conclusions

Almost 4 of 5 MIs in men may be preventable with a combined low-risk behavior.     

Recombinant human erythropoietin in very elderly patients with myelodysplastic syndromes: results from a retrospective study

Myelodysplastic syndromes (MDS) are common in elderly patients. Recombinant human erythro-poietin (rHuEPO) has been widely used to treat anemia in lower risk MDS patients, but few data are known about rHuEPO treatment in the very elderly patient group. In order to investigate the role of rHuEPO treatment in terms of response, overall survival (OS), and toxicity in a very elderly MDS patient group, 93 MDS patients treated with rHuEPO when aged ≥80 years were selected among MDS cases enrolled in a retrospective multicenter study by the cooperative group Gruppo Romano Mielodisplasie (GROM) from Jan 2002 to Dec 2010. At baseline, median age was 82.7 (range 80–99.1) with a median hemoglobin (Hb) level of 9 g/dl (range 6–10.8). The initial dose of rHuEPO was standard (epoetin alpha 40,000 IU/week or epoetin beta 30,000 IU/week) in 59 (63.4 %) pa-tients or high in 34 (36.6 %) (epoetin alpha 80,000 IU/week) patients. We observed an erythroid response (ER) in 59 (63.4 %) patients. No thrombotic event was reported. Independent predictive factors for ER were low transfusion requirement before treatment (p?=?0.004), ferritin <200 ng/ml (p?=?0.017), Hb >8 g/dl (p?=?0.034), and a high-dose rHuEPO treatment (p?=?0.032). Median OS from rHuEPO start was 49.3 months (95 % CI 27.5–68.4) in responders versus 30.6 months (95 % CI 7.3–53.8) in resistant patients (p?=?0.185). In conclusion, rHuEPO treatment is safe and effective also in the very elderly MDS patients. However, further larger studies are warranted to evaluate if EPO treatment could be worthwhile in terms of quality of life and cost-efficacy in very old patients.