Short-Term Environmental Enrichment Rescues Adult Neurogenesis and Memory Deficits in APPSw,Ind Transgenic Mice

Epidemiological studies indicate that intellectual activity prevents or delays the onset of Alzheimer's disease (AD). Similarly, cognitive stimulation using environmental enrichment (EE), which increases adult neurogenesis and functional integration of newborn neurons into neural circuits of the hippocampus, protects against memory decline in transgenic mouse models of AD, but the mechanisms involved are poorly understood. To study the therapeutic benefits of cognitive stimulation in AD we examined the effects of EE in hippocampal neurogenesis and memory in a transgenic mouse model of AD expressing the human mutant β-amyloid (Aβ) precursor protein (APPSw,Ind). By using molecular markers of new generated neurons (bromodeoxiuridine, NeuN and doublecortin), we found reduced neurogenesis and decreased dendritic length and projections of doublecortin-expressing cells of the dentate gyrus in young APPSw,Ind transgenic mice. Moreover, we detected a lower number of mature neurons (NeuN positive) in the granular cell layer and a reduced volume of the dentate gyrus that could be due to a sustained decrease in the incorporation of new generated neurons. We found that short-term EE for 7 weeks efficiently ameliorates early hippocampal-dependent spatial learning and memory deficits in APPSw,Ind transgenic mice. The cognitive benefits of enrichment in APPSw,Ind transgenic mice were associated with increased number, dendritic length and projections to the CA3 region of the most mature adult newborn neurons. By contrast, Aβ levels and the total number of neurons in the dentate gyrus were unchanged by EE in APPSw,Ind mice. These results suggest that promoting the survival and maturation of adult generated newborn neurons in the hippocampus may contribute to cognitive benefits in AD mouse models

Mechanistic Insights into Growth of Surface-Mounted Metal-Organic Framework Films Resolved by Infrared (Nano-) Spectroscopy

Control over assembly, orientation, and defect-free growth of metal-organic framework (MOF) films is crucial for their future applications. A layer-by-layer approach is considered a suitable method to synthesize highly oriented films of numerous MOF topologies, but the initial stages of the film growth remain poorly understood. Here we use a combination of infrared (IR) reflection absorption spectroscopy and atomic force microscopy (AFM)-IR imaging to investigate the assembly and growth of a surface mounted MOF (SURMOF) film, specifically HKUST-1. IR spectra of the films were measured with monolayer sensitivity and <10 nm spatial resolution. In contrast to the common knowledge of LbL SURMOF synthesis, we find evidence for the surface-hindered growth and large presence of copper acetate precursor species in the produced MOF thin-films. The growth proceeds via a solution-mediated mechanism where the presence of weakly adsorbed copper acetate species leads to the formation of crystalline agglomerates with a size that largely exceeds theoretical growth limits. We report the spectroscopic characterization of physisorbed copper acetate surface species and find evidence for the large presence of unexchanged and mixed copper-paddle-wheels. Based on these insights, we were able to optimize and automatize synthesis methods and produce (100) oriented HKUST-1 thin-films with significantly shorter synthesis times, and additionally use copper nitrate as an effective synthesis precursor

Mechanistic Insights into Growth of Surface-Mounted Metal-Organic Framework Films Resolved by Infrared (Nano-) Spectroscopy

Control over assembly, orientation, and defect-free growth of metal-organic framework (MOF) films is crucial for their future applications. A layer-by-layer approach is considered a suitable method to synthesize highly oriented films of numerous MOF topologies, but the initial stages of the film growth remain poorly understood. Here we use a combination of infrared (IR) reflection absorption spectroscopy and atomic force microscopy (AFM)-IR imaging to investigate the assembly and growth of a surface mounted MOF (SURMOF) film, specifically HKUST-1. IR spectra of the films were measured with monolayer sensitivity and <10 nm spatial resolution. In contrast to the common knowledge of LbL SURMOF synthesis, we find evidence for the surface-hindered growth and large presence of copper acetate precursor species in the produced MOF thin-films. The growth proceeds via a solution-mediated mechanism where the presence of weakly adsorbed copper acetate species leads to the formation of crystalline agglomerates with a size that largely exceeds theoretical growth limits. We report the spectroscopic characterization of physisorbed copper acetate surface species and find evidence for the large presence of unexchanged and mixed copper-paddle-wheels. Based on these insights, we were able to optimize and automatize synthesis methods and produce (100) oriented HKUST-1 thin-films with significantly shorter synthesis times, and additionally use copper nitrate as an effective synthesis precursor

Weight loss in patients taking felbamate

Felbamate is a new antiepileptic drug (AED) with a good safety profile. Anorexia has been reported in patients taking felbamate, but the incidence and severity of this side effect have not been adequately investigated. We studied 65 patients with intractable seizures who received adjunctive felbamate therapy as part of clinical research trials or in a compassionate-use program. Mean treatment time on felbamate was 23 weeks (+/- SD 16; range, 6-116 weeks). Forty-nine patients (75%) lost weight during the trials. For subjects older than 15 years, there was a mean weight loss of 3.17 kg or 4.11% of body weight (T = 191.5, z = 4.18, p 4 kg, and seven patients (11%) lost > 8 kg. Adjunctive treatment of adults with severe epilepsy with felbamate may be associated with clinically significant weight loss

Combined effect of GSTM1 gene deletion, GSTT1 gene deletion and MTHFR C677T mutation in male infertility

The aim of the study was to investigate the association between the GSTM1 and GSTT1 gene deletion and MTHFR C677T mutation and male infertility. The study has encompassed 52 infertile and 56 fertile males. Genotype distributions of GSTM1 and GSTT1 gene deletions and the MTHFR C677T mutation did not differ significantly among the analyzed groups, however, a difference in distribution of certain genotype combinations was observed. The obtained results indicate that carriers of double GSTM1/GSTT1 deletion and the MTHFR 677CC genotype are at higher risk of infertility than carriers of any other combination of genotypes (OR 3.5, 95%CI 0.68-18.30)