Short-term Changes in Self-rating Depression Scale Scores after Smoking Cessation in Neurotic Patients

Objective The psychological status is a key factor in smoking continuance. However, details on short-term changes in mild depressive states after smoking cessation (SC) are still unknown. The purpose of the present study was to investigate these short-term changes. Methods A total of 989 patients who visited our SC Clinic were assessed using the Zung Self-Rating-Depression-Scale (SDS), an official instrument to measure depressive tendencies. The participants were classified into normal and neurotic groups based on their SDS scores during their initial visit; they were assessed again 2, 4, 8, and 12 weeks thereafter. Results The majority of patients in the neurotic group were women. These patients were also younger, with a higher nicotine dependence, and presented with a lower successful SC rate than the patients in the normal group. A decrease in SDS scores after starting the SC treatment was observed only in the neurotic group, especially during the first two weeks. In patients who continued to smoke, no improvement in depressive tendencies was noted in this period. Conclusion Depressive tendencies of patients with neurosis improve in the initial stages of the SC treatment (i.e., within two weeks after starting the treatment). This finding fills the mentioned knowledge gap regarding the effects of SC on mild depressive states in the short term.     

Effect of radioactivity outside the field of view on image quality of dedicated breast positron emission tomography: preliminary phantom and clinical studies

Annals of Nuclear Medicine - Semi-quantitative positron emission tomography (PET) values, such as the maximum standardized uptake value (SUVmax), are widely used to identify malignant lesions and...     

Voxel-based analysis of age and gender effects on striatal [123I] FP-CIT binding in healthy Japanese adults

Annals of Nuclear Medicine - Although previous studies have investigated age and gender effects on striatal subregional dopamine transporter (DaT) binding, these studies were mostly based on a...     

Prostanoids in the Therapy of Glaucoma

Elevated intraocular pressure (IOP) is one of the most important risk factors for the development of glaucoma, which is a progressive optic neuropathy. Lowering IOP is currently the only therapeutic approach to the therapy of glaucoma. Since the use of pilocarpine eye drops for glaucoma treatment was reported in the late 1870s, academic researchers and pharmaceutical companies attempted to discover new drugs with more potent, prolonged, and safer IOP‐reducing effects. These persistent efforts finally paid off, and prostanoids with FP‐receptor agonist activity were found to be very potent IOP‐lowering agents. To date, three prostanoids (latanoprost, travoprost and bimatoprost) have been launched in many countries, and now a new FP‐receptor agonist, tafluprost, is entering clinical development. All of these prostanoids are superior to the β‐adrenoceptor antagonists in their IOP‐lowering efficacy, and no severe side effects have been reported in their long‐term clinical use. In addition, tafluprost may be expected to improve ocular blood flow. Hence, prostanoids currently occupy center stage among glaucoma medications. It cannot be denied that in terms of efficacy, safety, patient compliance, and medical economy prostanoids are currently the first‐line medicines among ocular antihypertensive drugs.     

ATP1A3 variants and slowly progressive cerebellar ataxia without paroxysmal or episodic symptoms in children

A heterogeneous spectrum of clinical manifestations caused by mutations in ATP1A3 have been previously described. Here we report two cases of infantile‐onset cerebellar ataxia, due to two different ATP1A3 variants. Both patients showed slowly progressive cerebellar ataxia without paroxysmal or episodic symptoms. Brain magnetic resonance imaging revealed mild cerebellar cortical atrophy in both patients. Whole exome sequencing revealed a de novo heterozygous variant in ATP1A3 in both patients. One patient had the c.460A>G (p.Met154Val) variant, while the other carried the c.1050C>A (p.Asp350Lys) variant. This phenotype was characterized by a slowly progressive cerebellar ataxia since the infantile period, which has not been previously described in association with ATP1A3 variants or in ATP1A3‐related clinical conditions. Our report contributes to extend the phenotypic spectrum of ATP1A3 mutations, showing paediatric slowly progressive cerebellar ataxia with mild cerebellar atrophy alone as an additional clinical presentation of ATP1A3‐related neurological disorders.     

The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation

The establishment of the epigenetic mark H4K20me1 (monomethylation of H4K20) by PR-Set7 during G₂/M directly impacts S-phase progression and genome stability. However, the mechanisms involved in the regulation of this event are not well understood. Here we show that SirT2 regulates H4K20me1 deposition through the deacetylation of H4K16Ac (acetylation of H4K16) and determines the levels of H4K20me2/3 throughout the cell cycle. SirT2 binds and deacetylates PR-Set7 at K90, modulating its chromatin localization. Consistently, SirT2 depletion significantly reduces PR-Set7 chromatin levels, alters the size and number of PR-Set7 foci, and decreases the overall mitotic deposition of H4K20me1. Upon stress, the interaction between SirT2 and PR-Set7 increases along with the H4K20me1 levels, suggesting a novel mitotic checkpoint mechanism. SirT2 loss in mice induces significant defects associated with defective H4K20me1–3 levels. Accordingly, SirT2-deficient animals exhibit genomic instability and chromosomal aberrations and are prone to tumorigenesis. Our studies suggest that the dynamic cross-talk between the environment and the genome during mitosis determines the fate of the subsequent cell cycle.     

E6-AP association promotes SOD1 aggresomes degradation and suppresses toxicity

Protein aggregation and ordered fibrillar amyloid deposition inside and outside of the central nervous system cells is the common pathologic hallmark of most aging-related neurodegenerative disorders. Dominant mutations in the gene encoding superoxide dismutase 1 (SOD1) protein are linked to familial amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by progressive degeneration of motor neurons, leading to muscle paralysis and death. The major histochemical hallmark in the remaining motor neurons of ALS is the intracellular accumulation of ubiquitinated inclusions consisting of insoluble aberrant protein aggregates. However, the molecular pathomechanisms underlying the process have been elusive. Here for the first time, we report that E6-AP, a homologous to E6-AP C terminus-type E3 ubiquitin ligase depleted in ALS mouse models before neurodegeneration. E6-AP coimmunoprecipitates with the SOD1 protein and is predominantly mislocalized in mutant SOD1-containing inclusion bodies. Overexpression of E6-AP increases the ubiquitination and facilitates degradation of SOD1 proteins. Finally, we show that the overexpression of E6-AP suppresses the aggregation and cell death mediated by mutated SOD1 proteins and cellular protective effect is more prominent when E6-AP is overexpressed along with Hsp70. These data suggest that enhancing the activity of E6-AP ubiquitin ligase might be a viable therapeutic strategy to eliminate mutant SOD1-mediated toxicity in ALS.     

Induction of Mutant Sik3Sleepy Allele in Neurons in Late Infancy Increases Sleep Need

Sleep is regulated in a homeostatic manner. Sleep deprivation increases sleep need, which is compensated mainly by increased EEG δ power during non-rapid eye movement sleep (NREMS) and, to a lesser extent, by increased sleep amount. Although genetic factors determine the constitutive level of sleep need and sleep amount in mice and humans, the molecular entity behind sleep need remains unknown. Recently, we found that a gain-of-function Sleepy (Slp) mutation in the salt-inducible kinase 3 (Sik3) gene, which produces the mutant SIK3(SLP) protein, leads to an increase in NREMS EEG δ power and sleep amount. Since Sik3^Slp mice express SIK3(SLP) in various types of cells in the brain as well as multiple peripheral tissues from the embryonic stage, the cell type and developmental stage responsible for the sleep phenotype in Sik3^Slp mice remain to be elucidated. Here, we generated two mouse lines, synapsin1^CreERT2 and Sik3^ex13flox mice, which enable inducible Cre-mediated, conditional expression of SIK3(SLP) in neurons on tamoxifen administration. Administration of tamoxifen to synapsin1^CreERT2 mice during late infancy resulted in higher recombination efficiency than administration during adolescence. SIK3(SLP) expression after late infancy increased NREMS and NREMS δ power in male synapsin1^CreERT2; Sik3^ex13flox/+ mice. The expression of SIK3(SLP) after adolescence led to a higher NREMS δ power without a significant change in NREMS amounts. Thus, neuron-specific expression of SIK3(SLP) after late infancy is sufficient to increase sleep.SIGNIFICANCE STATEMENT The propensity to accumulate sleep need during wakefulness and to dissipate it during sleep underlies the homeostatic regulation of sleep. However, little is known about the developmental stage and cell types involved in determining the homeostatic regulation of sleep. Here, we show that Sik3^Slp allele induction in mature neurons in late infancy is sufficient to increase non-rapid eye movement sleep amount and non-rapid eye movement sleep δ power. SIK3 signaling in neurons constitutes an intracellular mechanism to increase sleep.