A functional 5HT2A receptor polymorphism (His452Tyr) and memory performances in Alzheimer's disease

The functional His452Tyr polymorphism in the 5HT2A receptor has been described to be associated with verbal memory in healthy adults, with worse episodic memory performances in Tyr452 (T) carriers. The aim of our study was to investigate a possible effect of this polymorphism on memory performances in Alzheimer disease (AD). We enrolled 169 patients affected by probable AD. 5HT2A genotype was determined as previously described. According to their genotype, patients were divided in T carriers (?n = 111) and non-carriers (?n = 69). We evaluated the possible effect of 5HT2A polymorphism on verbal memory tasks. A one-way MANOVA analysis did not show a positive interaction between the two groups (?p > 0.05) at the baseline and at the follow-up. Nevertheless, the analyses of the single-task effect showed lower performances for non-T carriers only in Rey's recognition task. Recent data reported poorer memory performances in healthy subjects carrying the T variant, in age-dependent manner (no differences between T vs. nT carriers were observed for age >50 years). In our AD sample, we did not find significant differences in verbal memory scores in T vs. nT carriers while a significant difference was found only in attentional task. At variance with that in healthy subjects, no correlation has been found between memory profiles of AD patients and His452Tyr polymorphism.     

Alterations in the subcellular distribution of NADPH oxidase p47phox in hypothalamic paraventricular neurons following slow‐pressor angiotensin II hypertension in female mice with accelerated ovarian failure

At younger ages, women have a lower risk for hypertension than men, but this sexual dimorphism declines with the onset of menopause. These differences are paralleled in rodents following “slow‐pressor” angiotensin II (AngII) administration: young male and aged female mice, but not young females, develop hypertension. There is also an established sexual dimorphism both in the cardiovascular response to the neurohypophyseal hormone arginine vasopressin (AVP) and in the expression of oxidative stress. We examined the relationship between AngII‐mediated hypertension and the cellular distribution of the superoxide generating NADPH oxidase (NOX) in AVP‐expressing hypothalamic paraventricular nucleus (PVN) neurons in “menopausal” female mice. Dual‐labeling immunoelectron microscopy was used to determine whether the subcellular distribution of the organizer/adapter NOX p47^phox subunit is altered in PVN dendrites following AngII administered (14 days) during the “postmenopausal” stage of accelerated ovarian failure (AOF) in young female mice treated with 4‐vinylcyclohexene diepoxide. Slow‐pressor AngII elevated blood pressure in AOF females and induced a significant increase in near plasmalemmal p47^phox and a decrease in cytoplasmic p47^phox in PVN AVP dendrites. These changes are the opposite of those observed in AngII‐induced hypertensive male mice (Coleman et al. [2013] J. Neurosci. 33:4308‐4316) and may be ascribed in part to baseline differences between young females and males in the near plasmalemmal p47^phox on AVP dendrites seen in the present study. These findings highlight fundamental differences in the neural substrates of oxidative stress in the PVN associated with AngII hypertension in postmenopausal females compared with males. J. Comp. Neurol. 524:2251–2265, 2016. © 2015 Wiley Periodicals, Inc.     

11p15 duplication and 13q34 deletion with Beckwith–Wiedemann syndrome and factor VII deficiency

Here we report a patient with 11p15.4p15.5 duplication and 13q34 deletion presenting with Beckwith–Wiedemann syndrome (BWS) and moderate deficiency of factor VII (FVII). The duplication was initially diagnosed on methylation‐sensitive multiplex ligation‐dependent probe amplification. Array comparative genome hybridization confirmed its presence and indicated a 13q34 distal deletion. The patient's clinical symptoms, including developmental delay and facial dysmorphism, were typical of BWS with paternal 11p15 trisomy. Partial 13q monosomy in this patient is associated with moderate deficiency of FVII and may also overlap with a few symptoms of paternal 11p15 trisomy such as developmental delay and some facial features. To our knowledge this is the first report of 11p15.4p15.5 duplication associated with deletion of 13q34 and FVII deficiency. Moreover, this report emphasizes the importance of detailed clinical as well as molecular examinations in patients with BWS features and developmental delay.     

Multidimensional anatomy of ‘modern type depression’ in Japan: A proposal for a different diagnostic approach to depression beyond the DSM‐5

Japan's prototype of depression was traditionally a melancholic depression based on the premorbid personality known as shūchaku‐kishitsu proposed by Mitsuzo Shimoda in the 1930s. However, since around 2000, a novel form of depression has emerged among Japanese youth. Called ‘modern type depression (MTD)’ by the mass media, the term has quickly gained popularity among the general public, though it has not been regarded as an official medical term. Likewise, lack of consensus guidelines for its diagnosis and treatment, and a dearth of scientific literature on MTD has led to confusion when dealing with it in clinical practice in Japan. In this review article, we summarize and discuss the present situation and issues regarding MTD by focusing on historical, diagnostic, psychosocial, and cultural perspectives. We also draw on international perspectives that begin to suggest that MTD is a phenomenon that may exist not only in Japan but also in many other countries with different sociocultural and historical backgrounds. It is therefore of interest to establish whether MTD is a culture‐specific phenomenon in Japan or a syndrome that can be classified using international diagnostic criteria as contained in the ICD or the DSM. We propose a novel diagnostic approach for depression that addresses MTD in order to combat the current confusion about depression under the present diagnostic systems.     

干扰素调节因子-5的研究进展

干扰素调节因子-5能诱导IFN-α、IFN-β产生,也能促进IL-6、IL-12b、IL-17、IL-23、TNF等细胞因子的分泌,从而参与机体的免疫反应、细胞生长、细胞分化、细胞凋亡、肿瘤发生和细胞信号转导等过程.干扰素调节因子-5在人体许多疾病的发生、发展中起重要作用.深入研究干扰素调节因子-5有助于我们可以更好地阐明相关疾病的发病机制并为治疗这些相关疾病提供理论依据和相应的靶点.     

Is the presence of an uncleaved embryo on day 3 a useful predictor of outcomes following day 5 transfer?

Purpose

This study aimed to determine whether the presence of an uncleaved embryo on day 3 is predictive of cycle outcome after day 5 transfer (D5 ET).

Methods

In vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles from January 2013 to November 2014 with D5 ET were analyzed for the presence of at least one uncleaved embryo on day 3 (D3). Each index cycle (n = 70) was compared with two matched control cycles without uncleaved embryos. The main outcome measures included embryo quality, implantation rate, and clinical pregnancy rate.

Results

Fifty-nine of 3896 total embryos in this study were uncleaved on D3 (1.5 %). Cycles with uncleaved embryos had more oocytes retrieved (20.6 vs. 17.5), lower proportions of good quality embryos on D3 (52.4 vs. 66.1 %), and fewer usable embryos (transferred or frozen) on D5 (42.4 vs. 50.8 %). However, there were no significant differences in the incidence of cycles with a positive hCG, or in the rates of implantation, clinical pregnancy, or live birth.

Conclusions

Although an uncleaved embryo on D3 is associated with reduced conversion of sibling embryos to the blastocyst stage on D5, overall quality of those embryos forming blastocysts is not markedly decreased and clinical outcomes are not compromised.