Amphetamine-Induced Dopamine Release and Neurocognitive Function in Treatment-Naive Adults with ADHD

Converging evidence from clinical, preclinical, neuroimaging, and genetic research implicates dopamine neurotransmission in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The in vivo neuroreceptor imaging evidence also suggests alterations in the dopamine system in ADHD; however, the nature and behavioral significance of those have not yet been established. Here, we investigated striatal dopaminergic function in ADHD using [¹¹C]raclopride PET with a d-amphetamine challenge. We also examined the relationship of striatal dopamine responses to ADHD symptoms and neurocognitive function. A total of 15 treatment-free, noncomorbid adult males with ADHD (age: 29.87±8.65) and 18 healthy male controls (age: 25.44±6.77) underwent two PET scans: one following a lactose placebo and the other following d-amphetamine (0.3 mg/kg, p.o.), administered double blind and in random order counterbalanced across groups. In a separate session without a drug, participants performed a battery of neurocognitive tests. Relative to the healthy controls, the ADHD patients, as a group, showed greater d-amphetamine-induced decreases in striatal [¹¹C]raclopride binding and performed more poorly on measures of response inhibition. Across groups, a greater magnitude of d-amphetamine-induced change in [¹¹C]raclopride binding potential was associated with poorer performance on measures of response inhibition and ADHD symptoms. Our findings suggest an augmented striatal dopaminergic response in treatment-naive ADHD. Though in contrast to results of a previous study, this finding appears consistent with a model proposing exaggerated phasic dopamine release in ADHD. A susceptibility to increased phasic dopamine responsivity may contribute to such characteristics of ADHD as poor inhibition and impulsivity.     

Association of methylenetetrahydrofolate reductase polymorphisms with susceptibility to Alzheimer's disease

Background

Genetic risk factors play an important role in the pathogenesis of Alzheimer's disease (AD). In this case-control study, we examined the C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene and their correlation with this pathology.

Objective

To verify the association between MTHFR C677T and A1298C polymorphisms and Alzheimer's disease.

Method

This work was conducted as a case–control study. Cases consisted of thirty-eight patients and 100 individuals without dementia constituted the control group. Genotyping of MTHFR polymorphisms was performed on patients and controls.

Result

Genetic analyses did not indicate a significant association between the MTHFR C677T mutation and AD (C/T: 63.15% versus 39%, p = 0.087). However, the genotype prevalence of the missense variant MTHFR A1298C was significantly different between patients and controls (A/C: 55% versus 7%, p < 10⁻³). Our data suggest an association between the MTHFR A1298C mutation and AD; however, the MTHFR C677T mutation did not contribute to susceptibility for AD.

Conclusion

The MTHFR A1298C polymorphism is a possible risk factor for Alzheimer's disease.     

High responsivity and 1/f noise of an ultraviolet photodetector based on Ni doped ZnO nanoparticles

This study involves the novel fabrication of a high responsivity, fast response, and low-cost (UV) photodetector (PD) based on ZnO/Ni nanoparticles deposited on a glass substrate. The ZnO/Ni nanoparticles were synthesized using a polyol process. The structure and the morphology of the samples were characterized by X-ray diffraction (XRD) and Transmission Electron Microscopy (TEM). Optical properties were measured using UV-visible, diffuse reflectance and photoluminescence (PL) spectroscopy. The photodetector exhibited high photoresponse characteristics under 375 nm laser excitation. Our device shows a high responsivity (121 A W⁻¹) with rise time (about 5.52 s) and fall time (about 12 s) at a bias voltage of 1 V. The device exhibits excellent reproducibility and stability characteristics with time. The noise spectra obtained from the UV photodetector were caused by the 1/f noise. The noise-equivalent power (NEP) is 1.08 × 10⁻⁹ W. Thus, the polyol process can be a useful and effective method for improving the performance of ZnO/Ni UV photodetectors.

This study involves the novel fabrication of a high responsivity, fast response, and low-cost (UV) photodetector (PD) based on ZnO/Ni nanoparticles deposited on a glass substrate.     

Molecular genetic analysis of Tunisian patients with a classic form of 21-hydroxylase deficiency: identification of four novel mutations and high prevalence of Q318X mutation

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders mainly due to defects in the steroid 21-hydroxylase (CYP21) gene. To determine the mutational spectrum in the Tunisian CAH population, the CYP21 active gene was analyzed in 51 unrelated patients using our cascade strategy (digestion by restriction enzyme, sequencing). All patients had a classical form of 21-hydroxylase deficiency. Mutations were detected in over 94% of the chromosomes examined. The most frequent mutation in the Tunisian CAH population was found to be Q318X, with large prevalence (35.3%), in contrast to 0.5-13.8% described in other series. Incidence of other mutations does not differ, as previously described: large deletions (19.6%), mutation in intron 2 (17.6%), and I172N (10.8%). Four novel mutations were found in four patients with the salt-wasting form. These four novel mutations include three point mutations that have not been reported to occur in the CYP21P pseudogene: R483W, W19X, 2669insC, and one small conversion of DNA sequence from exon 5 to exon 8. Our results have shown a good genotype/phenotype correlation in the case of most mutations. This is the first report of screening for mutations of 21-hydroxylase gene in the Tunisian population and even in the Arab population.     

Investigation of optical and electrical properties of the semiconducting α-KZnPO4 compound

We used the solid state method to synthesize the α-KZnPO₄ compound. The X-ray diffraction pattern revealed that the sample represents a single hexagonal phase with a P6₃ space group. The chemical composition of the compound was examined by energy dispersive spectroscopy. The optical absorption measurement confirmed the semiconductor nature of the compound with a band gap around 4.52 eV. Furthermore, the electrical properties of the material were analyzed by means of the impedance spectroscopy, in a frequency range from 100 Hz to 1 MHz and a temperature range from 583 K to 673 K. The dependency of s(T) on temperature showed that the overlapping large polaron tunneling model is the mechanism responsible for AC conduction in the compound. A correlation between the crystal structure and the ionic conductivity was established and discussed. Finally, the temperature variation of M′′ peak showed a thermally activated relaxation process and a temperature-dependent stretching exponent β parameter.

We used the solid state method to synthesize the α-KZnPO₄ compound.     

Novel RAB3GAP1 Mutation in the First Tunisian Family With Warburg Micro Syndrome

Background and PurposeWarburg Micro syndrome (WARBM) is a rare autosomal recessive genetic disease characterized by ocular, neurologic, and endocrine anomalies. WARBM is a phenotypically and genetically heterogeneous syndrome caused by mutations in RAB3GAP1, RAB3GAP2, RAB18, and TBC1D20. Here we present the clinical and genetic characterization of a consanguineous Tunisian family with a WARBM phenotype presenting two pathogenic variations, one of which is on RAB3GAP1.MethodsWe applied whole-exome sequencing (WES) to two affected young males presenting a WARBM-compatible phenotype.ResultsWe reveal a new variation in RAB3GAP1 ({"type":"entrez-nucleotide","attrs":{"text":"NM_012233.3","term_id":"1677500243"}}NM_012233.3: c.297del, p.Gln99fs) and another variation in ABCD1 ({"type":"entrez-nucleotide","attrs":{"text":"NM_000033","term_id":"1519313321"}}NM_000033: c.896A>G, p.His299Arg). Each of these mutations, which in silico predictions concluded as being pathogenic variations, affects a critical protein region. Both affected males presented a WARBM-compatible phenotype, with severe intellectual disability, severe developmental delay, postnatal growth delay, postnatal microcephaly, congenital bilateral cataracts, general hypotonia, and a thin corpus callosum without a splenium. However, intrafamilial clinical heterogeneity was present, since only the oldest child had large ears, microphthalmia, foot deformities, and a genital anomaly, and only the youngest child had microcornea. Despite the mutation identified in ABCD1, our patients did not have any X-linked symptoms of adrenoleukodystrophy disorder that are usually caused by ABCD1 mutations, which prompted our interest in clinical monitoring.ConclusionsWES analysis of a consanguineous Tunisian family with WARBM revealed a novel variation in RAB3GAP1 ({"type":"entrez-nucleotide","attrs":{"text":"NM_012233.3","term_id":"1677500243"}}NM_012233.3: c.297del, p.Gln99fs) that is most likely pathogenic and allowed us to confirm the diagnosis of WARBM.     

Effects of Permethrin on Biomarkers in Mediterranean Clams (Ruditapes decussatus)

The present study was focused on the assessment of Catalase (CAT) and Acetylcholinesterase (AChE) activities in Mediterranean clams (Ruditapes decussatus) exposed to 50, 100 and 150 μg/L of Permethrin for 5, 10, 15, 20 and 25 days. In water, the measured concentrations of Permethrin in the treated aquariums were respectively 16.66, 38.24 and 55.61 μg/L. Results showed that CAT activity was increased after 5 days of exposure to high concentration reaching maximum value of 10.14 μmol/min/mg proteins after 25 days. However, no significant changes in AChE activity after 5 days of exposure were detected in all treated groups. AChE activity was significantly inhibited after 10 days with 100 and 150 μg/L and still depending on concentration and time. Maximum inhibition of AChE activity was reached after 25 days with the highest concentration of Permethrin. Our data indicated that exposure to Permethrin modifies biomarker profiles inducing oxidative stress and reducing AChE activity in Mediterranean clams.