Foxo3 is required for the regulation of oxidative stress in erythropoiesis

Erythroid cells accumulate hemoglobin as they mature and as a result are highly prone to oxidative damage. However, mechanisms of transcriptional control of antioxidant defense in erythroid cells have thus far been poorly characterized. We observed that animals deficient in the forkhead box O3 (Foxo3) transcription factor died rapidly when exposed to erythroid oxidative stress-induced conditions, while wild-type mice showed no decreased viability. In view of this striking finding, we investigated the potential role of Foxo3 in the regulation of ROS in erythropoiesis. Foxo3 expression, nuclear localization, and transcriptional activity were all enhanced during normal erythroid cell maturation. Foxo3-deficient erythrocytes exhibited decreased expression of ROS scavenging enzymes and had a ROS-mediated shortened lifespan and evidence of oxidative damage. Furthermore, loss of Foxo3 induced mitotic arrest in erythroid precursor cells, leading to a significant decrease in the rate of in vivo erythroid maturation. We identified ROS-mediated upregulation of P21(CIP1/WAF1/Sdi1) (also known as Cdkn1a) as a major contributor to the interference with cell cycle progression in Foxo3-deficient erythroid precursor cells. These findings establish an essential nonredundant function for Foxo3 in the regulation of oxidative stress, cell cycle, maturation, and lifespan of erythroid cells. These results may have an impact on the understanding of human disorders in which ROS play a role

Association of serum brain derived neurotropic factor with duration of drug-naive period and positive-negative symptom scores in drug naive schizophrenia

<div><p>Introduction</p><p>The aim of this study was to compare the serum brain derived neurotropic factor (BNDF) levels of patients with schizophrenia who had never received an antipsychotic treatment with those of a control group. Also, to analyze the relationship between the Positive and Negative Symptom Scale (PANSS) scores and BDNF levels of the patients during the period they were drug-naive.</p><p>Materials and methods</p><p>The sample of the study comprised patients who presentedto the Psychiatry Clinic and were admitted after a distinctive schizophrenia diagnosis was made in accordance with the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) diagnosis classification and who were not using and never had any antipsychotic medicine. A total of 160 participants were included in the study, 80 of whom had schizophrenia patients and 80 constituted the age- and sex-matched healthy control group. Before the start of the treatment, the serum samples to be checked for the BDNF levels were collected from the patients.</p><p>Results</p><p>The difference between the average BDNF levels of the groups were statistically significant (t = -5.25; p˂.001). An analysis as to whether there was a relation between the BDNF levels and the drug-naïve duration indicated no correlations. An examination of the relationship between PANSS scores and BDNF levels of the patients yielded no correlations.</p><p>Discussion</p><p>Serum BDNF levels seem to be one of the indicators of schizophrenia and its progress; nevertheless, we still do not have sufficient information about this neurotropic factor. In light of our study, the neurodevelopmental changes that occur at disease onset of the illness prominently affect the progress of the illness, which highlights the importance of the treatment in the early stages.</p></div

The clinical features of the patients participating in the study.

<p>The clinical features of the patients participating in the study.</p

Comparison of BDNF and PANSS scores between the different drug-naïve duration groups.

<p>Comparison of BDNF and PANSS scores between the different drug-naïve duration groups.</p

Demographical features of the participating patients and control group.

<p>Demographical features of the participating patients and control group.</p

Dot plot of control and patients groups.

<p>Dot plot of control and patients groups.</p

Suicidal hanging in Istanbul, Turkey: 1979-2012 Autopsy results

WOS: 000355681900010PubMed ID: 26048496A retrospective study was carried out on 4549 which is the total number of hanging cases autopsied at Forensic Medicine Institute in Istanbul, Turkey. 4502 hanging cases of suicidal origin were detected and evaluated in terms of demographic features, the type of hanging material used for ligature, internal findings in neck organs, toxicological findings and microscopic findings. Of these suicides, 3295 (73.2%) were males and 1207 (26.8%) were females. The average age of the victims was 37.8 (SD 1.6). Crude suicidal hanging rate is approximately two-fold increase in women, while it is about five-to six-fold increase in men during 33 years. 1424 of the victims committed suicide by hanging themselves at home, and 441 of them in prison and indoor areas. The alcohol in the blood of all autopsy victims was tested and results were positive for 687 people. A drug active agent was detected in 108 (2.4%) victims: 70 (1.5%) of them were antidepressants, 20 (0.5%) of them were analgesic/anti-inflammatory/anti-histaminic and 18 (0.4%) of them were antipsychotic. In the examination of the psychoactive substances in blood and urine, any of such substances was not detected in 4146 of the victims. However, victims' blood and urine contained a sedative-hypnotic-anxiolytic with 74 (1.6%), a cannabinoid with 16 (0.4%) and an opioid with 12 (0.3%). Psychoactive substance examination was not carried out for 243 victims. Of these cases, 4060 (90.2%), ecchymosis in soft tissues and 2800 (62.1%) fracture in neck organs was found. (C) 2015 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved

Adult Foot Macrodactyly: A Case Report and Review of the Literature

Macrodactyly of the foot is a rare congenital anomaly characterized by an enlargement of the soft tissue and osseous elements. It is difficult to treat this disorder when both the functional and cosmetic problems are addressed simultaneously. In the presented case, we describe an adult male patient with macrodactyly of the great toe, who underwent surgical correction consisting of amputation with debulking of soft tissues. To our knowledge, only a few cases regarding adults with macrodactyly of the foot have been reported in the literature. We advocate early surgical treatment of macrodactyly of the foot to enhance the quality of social life. [Arch Clin Exp Surg 2014; 3(2.000): 123-128