Concentrations plasmatiques des glutathions et leurs corrélations avec les caractéristiques cliniques et thérapeutiques des patients atteints de schizophrénie

IntroductionAltered glutathione systems (GSH) are suggested to participate in the pathophysiology of schizophrenia. The purpose of this study was to determine the plasmatic glutathione levels of patients with schizophrenia compared to healthy controls and to examine their relationships with clinical and therapeutic features.MethodsIt was a case-control study carried out on 100 patients with schizophrenia according to DSM-IV-TR criteria and 95 healthy controls. All patients were assessed by Clinical Global Impressions-severity (CGI-severity) and Global Assessment of Functioning (EGF). Most of the patients (55%) were under first-generation antipsychotics. Plasmatic glutathione levels (total glutathione GSHt, reduced glutathione GSHr, oxidized glutathione GSSG) were determined by spectrophotometry.ResultsThe levels of GSHt and GSHr were significantly decreased in schizophrenic patients in comparison with the healthy controls. These reductions were noted to be more pronounced in the untreated patients. No correlation was observed between the GSH levels and the clinical subtypes of schizophrenia and EGF scores. Depending on the therapeutic status, there were no significant differences in the GSH levels. In addition, there was no correlation between the GSH levels and the daily dosage of the antipsychotic treatment.ConclusionOur results suggest that the observed changes are related to the physiopathology of schizophrenia rather than to the presence of neuroleptic treatment. These results provide support for further studies of the possible role of antioxidants as neuroprotective therapeutic strategies.     

An analysis of the continuing professional development needs of radiographers and radiation therapists in Singapore

IntroductionContinuing Professional development (CPD) is deemed essential for the Radiographers (DR) and Radiation Therapists (RT) after Singapore commenced state registration. Diagnostic imaging and radiotherapy treatment services are constantly revolutionizing and those working in this field requires sufficient knowledge of the uptrends for training and development. The purpose of this survey is to identify the current training needs of the registered DR and RT in Singapore, and to understand their views about CPD activities.MethodsAn online questionnaire was disseminated by the Singapore Society of Radiographers (SSR) to all registered DR and RT in Singapore, and all practicing in restructured and private hospitals were included. Data collection took place from January 2018 to April 2018.Results102 responses were analysed, where 89 were DR and 13 were RT. CPD was provided in 72.5% (n = 74) of the participants’ institutions, and 69.6% (n = 71) of participants were aware of CPD. Interestingly, participants were significantly more likely to be unaware of CPD when working in an institution which do not offer CPD. Training programme objective was the most important factor for selecting a programme. 93.1% (n = 95) preferred SSR to support them for CPD. There were a few constraints to CPD engagements identified such as financial factors, lack of time, and institution availability.ConclusionThere was significant intrinsic motivation in a quality CPD activity. CPD activities should be current, accessible and relevant for the healthcare professionals to increase participation, which directly contributes to high standards of clinical care.Implications for practiceLocal healthcare institutions should be aware and address needs, gaps and aspirations of the local DR and RT community to ensure adequate preparation has been made upon initiation of mandatory CPD.     

Morphometry and localization of the temporal transverse Heschl’s gyrus in magnetic resonance imaging: a guide for cortical stimulation of chronic tinnitus

Purpose

Subjective tinnitus is considered a phantom auditory phenomenon. Recent studies show that electrical or magnetic stimulation of the cortex can alleviate some tinnitus. The usual target of the stimulation is the primary auditory cortex (PAC) on Heschl’s gyrus (HG). The objective of this study was to specify the anatomy of HG by magnetic resonance imaging (MRI).

Methods

Cerebral MRI of 60 patients with chronic tinnitus, carried out before neuronavigated repetitive transcranial magnetic stimulation targeting the auditory cortex, were included. 3D-T1 MRI was reformatted in Talairach–Tournoux’s stereotactic space, then the following steps were performed: morphometry of HG, localization of the probabilistic center of the PAC (pcPAC) chosen at the junction between the medial third and the lateral two-thirds of HG, relative to external and cortical landmarks, and identification of its coordinates relative to the bicommissural line (AC-PC).

Results

In relation to external landmarks, the pcPAC was identified around 5 cm above the root of the helix of the ear in the direction of a point on the vertex located 4 cm behind the coronal suture, for both sides. In Talairach–Tournoux’s stereotactic space with the anterior commissure as the origin, the pcPAC coordinates were x = 43, y = ?20, z = 6.8 on the right side, and x = ?42.5, y = ?21.5, and z = 6.5 on the left. Probabilistic maps of the presence of HG pointed to a relative contraction of data in space, despite inter- and intraindividual differences.

Conclusion

The choice of our stimulation target was established in the middle of the theoretical position of the PAC. MRI allows a reliable identification of the target structure.     

Mutation in Osteoactivin Decreases Bone Formation in Vivo and Osteoblast Differentiation in Vitro

We have previously identified osteoactivin (OA), encoded by Gpnmb, as an osteogenic factor that stimulates osteoblast differentiation in vitro. To elucidate the importance of OA in osteogenesis, we characterized the skeletal phenotype of a mouse model, DBA/2J (D2J) with a loss-of-function mutation in Gpnmb. Microtomography of D2J mice showed decreased trabecular mass, compared to that in wild-type mice [DBA/2J-Gpnmb⁺/SjJ (D2J/Gpnmb⁺)]. Serum analysis showed decreases in OA and the bone-formation markers alkaline phosphatase and osteocalcin in D2J mice. Although D2J mice showed decreased osteoid and mineralization surfaces, their osteoblasts were increased in number, compared to D2J/Gpnmb⁺ mice. We then examined the ability of D2J osteoblasts to differentiate in culture, where their differentiation and function were decreased, as evidenced by low alkaline phosphatase activity and matrix mineralization. Quantitative RT-PCR analyses confirmed the decreased expression of differentiation markers in D2J osteoblasts. In vitro, D2J osteoblasts proliferated and survived significantly less, compared to D2J/Gpnmb⁺ osteoblasts. Next, we investigated whether mutant OA protein induces endoplasmic reticulum stress in D2J osteoblasts. Neither endoplasmic reticulum stress markers nor endoplasmic reticulum ultrastructure were altered in D2J osteoblasts. Finally, we assessed underlying mechanisms that might alter proliferation of D2J osteoblasts. Interestingly, TGF-β receptors and Smad-2/3 phosphorylation were up-regulated in D2J osteoblasts, suggesting that OA contributes to TGF-β signaling. These data confirm the anabolic role of OA in postnatal bone formation.Osteoporosis is a growing public health problem, in part because of the increasing numbers of people living beyond the age of 65 years.¹ It is characterized by low bone mass due to increased bone resorption by osteoclasts and decreased bone formation by osteoblasts, with significant deterioration in the bone microarchitecture leading to high bone fragility and increased fracture risk.^1,2 The net effect of osteoporosis is low bone mass.¹ There is an increasing demand for identifying novel bone anabolic factors with potential therapeutic benefits in treating generalized bone loss, such as osteoporosis and/or major skeletal fracture.Osteoactivin is a novel glycoprotein first identified in natural mutant osteopetrotic rats.³ The same protein has been identified and named separately in several other species: as dendritic cell heparan sulfate proteoglycan integrin dependent ligand (DCHIL) in mouse dendritic cells,⁴ as transmembrane glycoprotein NMB (GPNMB) in human melanoma cell lines and melanocytes,⁵ and as hematopoietic growth factor inducible neurokinin (HGFIN) in human tumor cells.⁶ The current recommended name for the protein encoded by Gpnmb in mouse is transmembrane glycoprotein NMB (http://www.ncbi.nlm.nih.gov/protein/Q99P91.2); here, we continue to use osteoactivin (OA) for the protein and Gpnmb for the gene. OA is a type I transmembrane protein that consists of multiple domains, including an extracellular domain, transmembrane domain, and protein sorting signal sequence.⁷ Within the C-terminal domain, OA has an RGD motif, predicting an integrin attachment site.^3,7–9Our research group initially reported on the novel role of OA in osteoblast differentiation and function.^7–10 We demonstrated that OA expression has a temporal pattern during osteoblast differentiation, being highest during matrix maturation and culture mineralization in vitro.^7–11 Using loss-of–function and gain-of–function approaches in osteoblasts, we reported that OA overexpression increases osteoblast differentiation and function and that OA down-regulation decreases nodule formation, alkaline phosphatase (ALP) activity, osteocalcin (OC) production, and matrix mineralization in vitro.⁷ We also reported on the positive role of OA in mesenchymal stem cell (MSCs) differentiation into osteoblasts in vitro.¹² In another study, we showed that recombinant OA protein induces higher osteogenic potential of fetal-derived MSCs, compared with bone marrow–derived MSCs¹³ and its osteogenic effects in the mouse C3H10T1/2 MSC cell line were similar to those of recombinant BMP-2.¹² We also localized OA protein as associated predominately with osteoblasts lining trabecular bones in vivo,¹¹ and showed that local injection of recombinant OA increased bone mass in a rat model.¹⁴ Moreover, in a fracture repair model OA expression increased over time, reaching a maximum 2 weeks after fracture.¹¹ In a parallel study, recombinant OA supported bone regeneration and formation in a rat critical-size calvarial defect model.¹⁵ Others have shown that OA is highly expressed by osteoclasts in vitro, suggesting that it may regulate osteoclast formation and activity.¹⁶There is urgent need for an animal model to fully examine the role of OA in osteogenesis. Interestingly, a natural mutation of the Gpnmb gene has been identified in the DBA/2J (D2J) mouse strain.¹⁷ These mice exhibit high-frequency hearing loss, which begins at the time of weaning and becomes severe by 2 to 3 months of age.^18,19 Aged D2J mice also develop progressive eye abnormalities that closely mimic human hereditary glaucoma. The onset of disease symptoms falls roughly between 3 and 4 months of age, and disease becomes severe by 6 months of age.^5,20 D2J mice are homozygous for a nonsense mutation in the Gpnmb gene sequence that induces an early stop codon, generating a truncated protein sequence of 150 amino acids (aa) instead of the full-length 562-aa OA protein.⁵ The control for the D2J mouse is the wild-type DBA/2J-Gpnmb⁺/SjJ mouse (D2J/Gpnmb⁺), homozygous for the wild-type Gpnmb gene.²¹ These Gpnmb wild-type mice do not develop glaucoma, as D2J mice do, although they exhibit mild iris stromal atrophy.²¹In the present study, we used Gpnmb mutant (D2J) and Gpnmb wild-type (D2J/Gpnmb⁺) mice to gain insight into the role of OA in osteogenesis and in osteoblast differentiation and function. Here, we report that loss-of–function mutation of Gpnmb suppresses bone formation by directly affecting osteoblast proliferation and survival, leading to a decreased number of differentiated osteoblasts with suppressed activity in bone mineralization. Thus, our data point to OA as a novel and positive regulator of postnatal bone formation.     

Smoking prevention and cessation in the Africa and Middle East region: a consensus draft guideline for healthcare providers--executive summary

Despite the abundance of scientific evidence confirming the health consequences of smoking and other forms of tobacco use, the tobacco epidemic remains an important public health problem and by 2030 it is predicted that more than 80% of tobacco deaths will be in developing countries. In Africa and the Middle East, many local factors contribute to the initiation and maintenance of tobacco use. Although efforts to reduce the mortality and morbidity associated with smoking and tobacco dependence are underway, there is a need for guidance on how to utilize appropriate tobacco control policies and psychology- and pharmacology-based therapies to counter tobacco dependence as recommended by the Framework Convention on Tobacco Control (FCTC). A group of tobacco cessation experts from public health services and/or academic institutions in Africa and the Middle East participated in a series of four meetings held in Cairo, Cape Town, and Dubai between May 2008 and February 2011 to develop a draft guideline tailored to their region. This article provides the background to the development of this draft smoking cessation guideline and discusses how the recommendations can be implemented and progress monitored to promote both primary prevention and cessation of tobacco use within our countries. The draft guideline for Africa and the Middle East provides an important resource in combating the devastating effects of tobacco use in these regions which can be further localized through engagement with local stakeholders in the countries of the region.     

Screening of SLC26A4 gene in autoimmune thyroid diseases

The Pendred syndrome (PS) gene, SLC26A4, was involved in the genetic susceptibility of autoimmune thyroid disease (AITD) in Tunisian population. Recently, functional assays have shown a differential expression of SLC26A4 gene between Graves’ disease (GD) and Hashimoto's thyroiditis (HT). Here, by the mean of DHPLC and HRM, we explored the 21 exons and their flanking intronic sequences of 128 patients affected with GD (n = 64) or HT (n = 64). The pathogenic effect of identified variations on splice was investigated using the web server HSF. Eighteen allelic variations were identified and ranged on missense, sens and splice variations. Nine identified variations (c.‐66C>G, c.898A>C, c.1002‐9A>C, c.1061T>C, c.1544 + 9G>T, c.1545‐5T>G, c.1790T>C, c.1826T>G, c.2139T>G) were previously reported in hearing impairment studies. Forty‐seven per cent (30/64) of GD patients and 37,5% (24/64) of HT patients present at least one variant in the explored sequences. Moreover, the analysis of the variant distribution between HT (9 (5′UTR), 12 exonic and 13 intronic) and GD (18 (5′UTR), 13 exonic and 5 intronic) patients showed a significant difference (χ² = 6.54, 2df, P = 0.03). Interestingly, missense changes (I300L, p.M283I, F354S and p.L597S) affected conserved residues of pendrin. On the other hand, the HSF analyses ascertain that some variants identified in HT disease are predicted to have a pathogenic effect on splice. In conclusion, our analysis of SLC26A4 sequence variations suggested a distinct genetics basis between HT and GD patients, which should be confirmed on a large cohort.     

Multicystic lung revealing a Sjogren's syndrome

The Sjogren's syndrome is a chronic inflammatory autoimmune disease that affects primarily the exocrine glands, but can affect other organs particularly the lungs. Cystic lung disease is very significant but exceptionally recounted in the literature. We report the case of a patient, 54 years old, whose disease was discovered incidentally after a routine chest radiograph. The diagnosis of cystic lung revealing a primary Sjogren's syndrome was held before a group of radio-clinical, immunological and histological arguments. Through our observation, the diagnosis of Sjogren's syndrome should be included in the list of diagnoses to raise in a multicystic lung.