The sand rat, Psammomys obesus, develops type 2 diabetic retinopathy similar to humans.

PURPOSE: Diabetic retinopathy (DR) is a leading cause of blindness, yet pertinent animal models are uncommon. The sand rat (Psammomys obesus), exhibiting diet-induced metabolic syndrome, might constitute a relevant model. METHODS: Adult P. obesus (n = 39) were maintained in captivity for 4 to 7 months and fed either vegetation-based diets (n = 13) or standard rat chow (n = 26). Although plant-fed animals exhibited uniform body weight and blood glucose levels over time, nearly 60% of rat chow-raised animals developed diabetes-like symptoms (test group). Animals were killed, and their eyes and vitreous were processed for immunochemistry. RESULTS: Compared with plant-fed animals, diabetic animals showed many abnormal vascular features, including vasodilation, tortuosity, and pericyte loss within the blood vessels, hyperproteinemia and elevated ratios of proangiogenic and antiangiogenic growth factors in the vitreous, and blood-retinal barrier breakdown. Furthermore, there were statistically significant decreases in retinal cell layer thicknesses and densities, accompanied by profound alterations in glia (downregulation of glutamine synthetase, glutamate-aspartate transporter, upregulation of glial fibrillar acidic protein) and many neurons (reduced expression of protein kinase Cα and Cξ in bipolar cells, axonal degeneration in ganglion cells). Cone photoreceptors were particularly affected, with reduced expression of short- and mid-/long-wavelength opsins. Hypercaloric diet nondiabetic animals showed intermediate values. CONCLUSIONS: Simple dietary modulation of P. obesus induces a rapid and severe phenotype closely resembling human type 2 DR. This species presents a valuable novel experimental model for probing the neural (especially cone photoreceptor) pathogenic modifications that are difficult to study in humans and for screening therapeutic strategies.

Quetiapine affects neuropeptide Y and corticotropin-releasing hormone in cerebrospinal fluid from schizophrenia patients: relationship to depression and anxiety symptoms and to treatment response.

Cumulative evidence indicates that neuropeptides play a role in the pathophysiology of schizophrenia. Early data showed increased neuropeptide Y (NPY) in cerebrospinal fluid (CSF) from schizophrenia patients and data from rodents show that antipsychotic drugs modulate NPY levels in and release from selected rat brain regions. In view of these findings we investigated whether the atypical antipsychotic quetiapine, originally used as an antipsychotic but subsequently shown to be efficient also in major depressive disorder and in both poles of bipolar disorder, would affect NPY-like immunoreactivity (-LI), and corticotropin-releasing hormone (CRH)-LI levels in CSF of schizophrenia patients. NPY-LI and CRH-LI in CSF were determined in 22 patients with schizophrenia. Lumbar puncture was performed at baseline and again after 4 wk of quetiapine treatment (600 mg/d). Patients were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and at weekly intervals. Quetiapine treatment was associated with a significant increase in NPY-LI (p<0.001) and decrease in CRH-LI (p<0.01). Stepwise multiple regression analysis revealed that ΔNPY-LI and ΔCRH-LI levels predicted 63% (p<0.001) of the variability of the ΔPANSS total score, ΔNPY-LI 42% (p<0.05) of the ΔPANSS anxiety items (G2) and ΔCRH-LI 40% (p=0.05) of the ΔPANSS depression items (G6). These results suggest that while quetiapine's effects on monoamines are probably related to its antipsychotic properties, the modulation of NPY and CRH accounts for its antidepressant and anxiolytic effects and can be markers of response.

O efeito do sorriso na percepção psicológica da pessoa

O objectivo do estudo foi o de verificar o efeito do sorriso na percepção psicológica da pessoa em jovens, adultos, idosos e jovens negros. Pretendia-se verificar se o sorriso contribui para os traços diferenciais entre os grupos humanos em estudo e se o mesmo era descritor de género. O estudo envolveu um delineamento transversal analítico ou estudo não-experimental, também classificado por estudo pós-facto, estudo de observação passiva ou estudo correlacional e de observação, de comparação entre grupos, mediante o juízo ou julgamento psicológico da face neutra e do tipo de sorriso contrastados, de matriz factorial 4 x 2 x 2 (face neutra, sorriso fechado, sorriso superior, sorriso largo; género dos estímulos; género dos respondentes) e a sua finalidade foi descrever a percepção psicológica do sorriso em função das variáveis género do estímulo, género do respondente e grupo étnico, na Escala de Percepção do Sorriso (EPS), em formato diferenciador semântico, com 19 itens bipolares opostos, tendo a avaliação sido feita numa escala ordinal de 1 a 7 pontos, nas dimensões Avaliação (12 itens) e Movimento Expressivo (7 itens) resultante dos estudos preliminares sobre a atractividade facial (estudo preliminar 1) e a escolha de dípolos de adjectivos preditores para percepção psicológica da face neutra (estudo preliminar 2). Nos estudos principais 1, 2 e 3 foram utilizados 24 estímulos fotográficos apresentando o tipo de sorriso (fechado, superior e largo) e a face neutra (12 do estímulo mulher e 12 do estímulo homem) referentes aos três grupos etários (18-25 anos, 40-50 anos e 60-70 anos) e a Escala de Percepção do Sorriso (EPS) foi aplicada a uma amostra não probabilística ou intencional do tipo homogénea de 480 participantes portugueses de ambos os géneros (240 mulheres e 240 homens) distribuídos por grupos etários de jovens (80 mulheres e 80 homens, média: 22.2 anos), adultos (80 mulheres e 80 homens, média: 43.1 anos) e idosos (80 mulheres e 80 homens, média: 65.0 anos) No estudo principal 4, foram utilizados 8 estímulos fotográficos apresentando o tipo de sorriso (fechado, superior e largo) e a face neutra (4 do estímulo mulher e 4 do estímulo homem) de universitários de Cabo Verde, a estudar em Portugal, e a Escala de Percepção do Sorriso (EPS) foi aplicada a uma amostra não probabilística ou intencional do tipo homogénea de 160 participantes de ambos os géneros (80 mulheres e 80 homens) e estudantes universitários portugueses (média: 21.8 anos). Os resultados revelam e confirmam o efeito do sorriso na percepção psicológica da pessoa, à semelhança de outros estudos, isto é, sorrir torna a percepção psicológica mais positiva ou negativa e verifica-se que tal sucede em função do género do estímulo e do género do respondente. As diferenças significativas na percepção da face neutra e tipo de sorriso contrastados são justificadas pela pertença de género de quem os percepciona e pela pertença do género de quem é percepcionado. Tal apenas não sucede no factor Avaliação do grupo dos adultos. Os resultados obtidos indicam que, quer no factor Avaliação quer no factor Movimento Expressivo, os tipos de sorriso largo e superior são os que registam médias ponderadas mais elevadas. Pelo contrário, a face neutra e o sorriso fechado registam valores menos elevados na percepção. A análise da percepção da pessoa em função da face neutra e tipo de sorriso contrastados revelou uma correspondência entre a expressão facial, o género do estímulo e o género do respondente. No factor Avaliação, a mulher é percepcionada mais positivamente que o homem, verificando-se o inverso no factor Movimento Expressivo no grupo dos adultos e dos idosos. Verificou-se efeito do sorriso na percepção psicológica dos estímulos de cor negra. No grupo dos jovens que percepcionaram estímulos de cor negra, o homem é considerado mais positivo que a mulher em ambos os factores. O efeito significativo do género revela que a sua percepção é condicionada pelo seu próprio género. Os resultados apontam ainda para a configuração pronunciada de uma hierarquização ascendente da face neutra e tipo de sorriso contrastados em dois conjuntos bem delimitados e distinguindo diferentes formas topográficas de sorrir: a face neutra e o sorriso fechado e o sorriso superior e o sorriso largo.

O efeito do sorriso na percepção psicológica da pessoa

O objectivo do estudo foi o de verificar o efeito do sorriso na percepção psicológica da pessoa em jovens, adultos, idosos e jovens negros. Pretendia-se verificar se o sorriso contribui para os traços diferenciais entre os grupos humanos em estudo e se o mesmo era descritor de género. O estudo envolveu um delineamento transversal analítico ou estudo não-experimental, também classificado por estudo pós-facto, estudo de observação passiva ou estudo correlacional e de observação, de comparação entre grupos, mediante o juízo ou julgamento psicológico da face neutra e do tipo de sorriso contrastados, de matriz factorial 4 x 2 x 2 (face neutra, sorriso fechado, sorriso superior, sorriso largo; género dos estímulos; género dos respondentes) e a sua finalidade foi descrever a percepção psicológica do sorriso em função das variáveis género do estímulo, género do respondente e grupo étnico, na Escala de Percepção do Sorriso (EPS), em formato diferenciador semântico, com 19 itens bipolares opostos, tendo a avaliação sido feita numa escala ordinal de 1 a 7 pontos, nas dimensões Avaliação (12 itens) e Movimento Expressivo (7 itens) resultante dos estudos preliminares sobre a atractividade facial (estudo preliminar 1) e a escolha de dípolos de adjectivos preditores para percepção psicológica da face neutra (estudo preliminar 2). Nos estudos principais 1, 2 e 3 foram utilizados 24 estímulos fotográficos apresentando o tipo de sorriso (fechado, superior e largo) e a face neutra (12 do estímulo mulher e 12 do estímulo homem) referentes aos três grupos etários (18-25 anos, 40-50 anos e 60-70 anos) e a Escala de Percepção do Sorriso (EPS) foi aplicada a uma amostra não probabilística ou intencional do tipo homogénea de 480 participantes portugueses de ambos os géneros (240 mulheres e 240 homens) distribuídos por grupos etários de jovens (80 mulheres e 80 homens, média: 22.2 anos), adultos (80 mulheres e 80 homens, média: 43.1 anos) e idosos (80 mulheres e 80 homens, média: 65.0 anos) No estudo principal 4, foram utilizados 8 estímulos fotográficos apresentando o tipo de sorriso (fechado, superior e largo) e a face neutra (4 do estímulo mulher e 4 do estímulo homem) de universitários de Cabo Verde, a estudar em Portugal, e a Escala de Percepção do Sorriso (EPS) foi aplicada a uma amostra não probabilística ou intencional do tipo homogénea de 160 participantes de ambos os géneros (80 mulheres e 80 homens) e estudantes universitários portugueses (média: 21.8 anos). Os resultados revelam e confirmam o efeito do sorriso na percepção psicológica da pessoa, à semelhança de outros estudos, isto é, sorrir torna a percepção psicológica mais positiva ou negativa e verifica-se que tal sucede em função do género do estímulo e do género do respondente. As diferenças significativas na percepção da face neutra e tipo de sorriso contrastados são justificadas pela pertença de género de quem os percepciona e pela pertença do género de quem é percepcionado. Tal apenas não sucede no factor Avaliação do grupo dos adultos. Os resultados obtidos indicam que, quer no factor Avaliação quer no factor Movimento Expressivo, os tipos de sorriso largo e superior são os que registam médias ponderadas mais elevadas. Pelo contrário, a face neutra e o sorriso fechado registam valores menos elevados na percepção. A análise da percepção da pessoa em função da face neutra e tipo de sorriso contrastados revelou uma correspondência entre a expressão facial, o género do estímulo e o género do respondente. No factor Avaliação, a mulher é percepcionada mais positivamente que o homem, verificando-se o inverso no factor Movimento Expressivo no grupo dos adultos e dos idosos. Verificou-se efeito do sorriso na percepção psicológica dos estímulos de cor negra. No grupo dos jovens que percepcionaram estímulos de cor negra, o homem é considerado mais positivo que a mulher em ambos os factores. O efeito significativo do género revela que a sua percepção é condicionada pelo seu próprio género. Os resultados apontam ainda para a configuração pronunciada de uma hierarquização ascendente da face neutra e tipo de sorriso contrastados em dois conjuntos bem delimitados e distinguindo diferentes formas topográficas de sorrir: a face neutra e o sorriso fechado e o sorriso superior e o sorriso largo.

Patterns of calcium-binding proteins support parallel and hierarchical organization of human auditory areas.

The human primary auditory cortex (AI) is surrounded by several other auditory areas, which can be identified by cyto-, myelo- and chemoarchitectonic criteria. We report here on the pattern of calcium-binding protein immunoreactivity within these areas. The supratemporal regions of four normal human brains (eight hemispheres) were processed histologically, and serial sections were stained for parvalbumin, calretinin or calbindin. Each calcium-binding protein yielded a specific pattern of labelling, which differed between auditory areas. In AI, defined as area TC [see C. von Economo and L. Horn (1930) Z. Ges. Neurol. Psychiatr.,130, 678-757], parvalbumin labelling was dark in layer IV; several parvalbumin-positive multipolar neurons were distributed in layers III and IV. Calbindin yielded dark labelling in layers I-III and V; it revealed numerous multipolar and pyramidal neurons in layers II and III. Calretinin labelling was lighter than that of parvalbumin or calbindin in AI; calretinin-positive bipolar and bitufted neurons were present in supragranular layers. In non-primary auditory areas, the intensity of labelling tended to become progressively lighter while moving away from AI, with qualitative differences between the cytoarchitectonically defined areas. In analogy to non-human primates, our results suggest differences in intrinsic organization between auditory areas that are compatible with parallel and hierarchical processing of auditory information.

Pial and arachnoid welding for restoration of normal cord anatomy after excision of intramedullary spinal cord tumors.

A significant postoperative problem in patients undergoing excision of intramedullary tumors is painful dysesthesiae, attributed to various causes, including edema, arachnoid scarring and cord tethering. The authors describe a technique of welding the pia and arachnoid after the excision of intramedullary spinal cord tumors used in seven cases. Using a fine bipolar forcep and a low current, the pial edges of the myelotomy were brought together and welded under saline irrigation. A similar method was used for closing the arachnoid while the dura was closed with a running 5-0 vicryl suture. Closing the pia and arachnoid restores normal cord anatomy after tumor excision and may reduce the incidence of postoperative painful dysesthesiae.

Estudio sobre prevalencia de a sarcopenia en una unidad de pacientes crónicos

la sarcopenia es un trastorno complejo, de etiología multifactorial que consta de la pérdida de masa corporal junto con una disminución de la fuerza y del rendimiento físico. Este estudio he evaluado la prevalencia de la sarcopenia en una población de 205 pacientes hospitalizados en una unidad de crónicos del Hospital La Fe de Valencia. También se ha evaluado la posible relación de la sarcopenia con otros factores como la comorbilidad, la discapacidad, la desnutrición, la disfagia orofaringea y las complicaciones intrahospitalarias. La prevalencia de sarcopenia fue muy elevada (76,4%), con porcentajes muy superiores a lo descrito en la literatura. También se encontró una relación estadísticamente significativa con la edad avanzada, la disminución de peso y de IMC, la disminución de la circunferencia braquial y la disfagia. Es necesario realizar estudios de carácter prospectivo y con una muestra superior de pacientes para alcanzar conclusiones más definitivas.

Differential vulnerability of neurochemically identified subpopulations of retinal neurons in a monkey model of glaucoma.

The vulnerability of subpopulations of retinal neurons delineated by their content of cytoskeletal or calcium-binding proteins was evaluated in the retinas of cynomolgus monkeys in which glaucoma was produced with an argon laser. We quantitatively compared the number of neurons containing either neurofilament (NF) protein, parvalbumin, calbindin or calretinin immunoreactivity in central and peripheral portions of the nasal and temporal quadrants of the retina from glaucomatous and fellow non-glaucomatous eyes. There was no significant difference between the proportion of amacrine, horizontal and bipolar cells labeled with antibodies to the calcium-binding proteins comparing the two eyes. NF triplet immunoreactivity was present in a subpopulation of retinal ganglion cells, many of which, but not all, likely correspond to large ganglion cells that subserve the magnocellular visual pathway. Loss of NF protein-containing retinal ganglion cells was widespread throughout the central (59-77% loss) and peripheral (96-97%) nasal and temporal quadrants and was associated with the loss of NF-immunoreactive optic nerve fibers in the glaucomatous eyes. Comparison of counts of NF-immunoreactive neurons with total cell loss evaluated by Nissl staining indicated that NF protein-immunoreactive cells represent a large proportion of the cells that degenerate in the glaucomatous eyes, particularly in the peripheral regions of the retina. Such data may be useful in determining the cellular basis for sensitivity to this pathologic process and may also be helpful in the design of diagnostic tests that may be sensitive to the loss of the subset of NF-immunoreactive ganglion cells.

Establishment of models to study mouse and human retinogenesis "in vitro" : isolation and characterization of retinal stem cells

SUMMARY IN FRENCH Les cellules souches sont des cellules indifférenciées capables a) de proliférer, b) de s'auto¬renouveller, c) de produire des cellules différenciées, postmitotiques et fonctionnelles (multipotencialité), et d) de régénérer le tissu après des lésions. Par exemple, les cellules de souches hematopoiétiques, situées dans la moelle osseuse, peuvent s'amplifier, se diviser et produire diverses cellules différenciées au cours de la vie, les cellules souches restant dans la moelle osseuse et consentant leur propriété. Les cellules souches intestinales, situées dans la crypte des microvillosités peuvent également régénérer tout l'intestin au cours de la vie. La rétine se compose de six classes de neurones et d'un type de cellule gliale. Tous ces types de cellules sont produits par un progéniteur rétinien. Le pic de production des photorécepteurs se situe autour des premiers jours postnatals chez la souris. A cette période la rétine contient les cellules hautement prolifératives. Dans cette étude, nous avons voulu analyser le phénotype de ces cellules et leur potentiel en tant que cellules souches ou progénitrices. Nous nous sommes également concentrés sur l'effet de certains facteurs épigéniques sur leur destin cellulaire. Nous avons observé que toutes les cellules prolifératives isolées à partir de neurorétines postnatales de souris expriment le marqueur de glie radiaire RC2, ainsi que des facteurs de transcription habituellement trouvés dans la glie radiaire (Mash1, Pax6), et répondent aux critères des cellules souches : une capacité élevée d'expansion, un état indifférencié, la multipotencialité (démontrée par analyse clonale). Nous avons étudié la différentiation des cellules dans différents milieux de culture. En l'absence de sérum, l'EGF induit l'expression de la β-tubulin-III, un marqueur neuronal, et l'acquisition d'une morphologie neuronale, ceci dans 15% des cellules présentes. Nous avons également analysé la prolifération de cellules. Seulement 20% des cellules incorporent le bromodéoxyuridine (BrdU) qui est un marqueur de division cellulaire. Ceci démontre que l'EGF induit la formation des neurones sans une progression massive du cycle cellulaire. Par ailleurs, une stimulation de 2h d'EGF est suffisante pour induire la différentiation neuronale. Certains des neurones formés sont des cellules ganglionnaires rétiniennes (GR), comme l'indique l'expression de marqueurs de cellules ganglionnaires (Ath5, Brn3b et mélanopsine), et dans de rare cas d'autres neurones rétiniens ont été observés (photorécepteurs (PR) et cellules bipolaires). Nous avons confirmé que les cellules souches rétiniennes tardives n'étaient pas restreintes au cours du temps et qu'elles conservent leur multipotencialité en étant capables de générer des neurones dits précoces (GR) ou tardifs (PR). Nos résultats prouvent que l'EGF est non seulement un facteur contrôlant le développement glial, comme précédemment démontré, mais également un facteur efficace de différentiation pour les neurones rétiniens, du moins in vitro. D'autre part, nous avons voulu établir si l'oeil adulte humain contient des cellules souches rétiniennes (CSRs). L'oeil de certains poissons ou amphibiens continue de croître pendant l'âge adulte du fait de l'activité persistante des cellules souches rétiniennes. Chez les poissons, le CSRs se situe dans la marge ciliaire (CM) à la périphérie de la rétine. Bien que l'oeil des mammifères ne se développe plus pendant la vie d'adulte, plusieurs groupes ont prouvé que l'oeil de mammifères adultes contient des cellules souches rétiniennes également dans la marge ciliaire plus précisément dans l'épithélium pigmenté et non dans la neurorétine. Ces CSRs répondent à certains critères des cellules souches. Nous avons identifié et caractérisé les cellules souches rétiniennes résidant dans l'oeil adulte humain. Nous avons prouvé qu'elles partagent les mêmes propriétés que leurs homologues chez les rongeurs c.-à-d. auto-renouvellement, amplification, et différenciation en neurones rétiniens in vitro et in vivo (démontré par immunocoloration et microarray). D'autre part, ces cellules peuvent être considérablement amplifiées, tout en conservant leur potentiel de cellules souches, comme indiqué par l'analyse de leur profil d'expression génique (microarray). Elles expriment également des gènes communs à diverses cellules souches: nucleostemin, nestin, Brni1, Notch2, ABCG2, c-kit et son ligand, aussi bien que cyclin D3 qui agit en aval de c-kit. Nous avons pu montré que Bmi1et Oct4 sont nécessaires pour la prolifération des CSRs confortant leur propriété de cellules souches. Nos données indiquent que la neurorétine postnatale chez la souris et l'épithélium pigmenté de la marge ciliaire chez l'humain adulte contiennent les cellules souches rétiniennes. En outre, nous avons développé un système qui permet d'amplifier et de cultiver facilement les CSRs. Ce modèle permet de disséquer les mécanismes impliqués lors de la retinogenèse. Par exemple, ce système peut être employé pour l'étude des substances ou des facteurs impliqués, par exemple, dans la survie ou dans la génération des cellules rétiniennes. Il peut également aider à disséquer la fonction de gènes ou les facteurs impliqués dans la restriction ou la spécification du destin cellulaire. En outre, dans les pays occidentaux, la rétinite pigmentaire (RP) touche 1 individu sur 3500 et la dégénérescence maculaire liée à l'âge (DMLA) affecte 1 % à 3% de la population âgée de plus de 60 ans. La génération in vitro de cellules rétiniennes est aussi un outil prometteur pour fournir une source illimitée de cellules pour l'étude de transplantation cellulaire pour la rétine. SUMMARY IN ENGLISH Stem cells are defined as undifferentiated cells capable of a) proliferation, b) self maintenance (self-renewability), c) production of many differentiated functional postmitotic cells (multipotency), and d) regenerating tissue after injury. For instance, hematopoietic stem cells, located in bone marrow, can expand, divide and generate differentiated cells into the diverse lineages throughout life, the stem cells conserving their status. In the villi crypt, the intestinal stem cells are also able to regenerate the intestine during their life time. The retina is composed of six classes of neurons and one glial cell. All these cell types are produced by the retinal progenitor cell. The peak of photoreceptor production is reached around the first postnatal days in rodents. Thus, at this stage the retina contains highly proliferative cells. In our research, we analyzed the phenotype of these cells and their potential as possible progenitor or stem cells. We also focused on the effect of epigenic factor(s) and cell fate determination. All the proliferating cells isolated from mice postnatal neuroretina harbored the radial glia marker RC2, expressed transcription factors usually found in radial glia (Mash 1, Pax6), and met the criteria of stem cells: high capacity of expansion, maintenance of an undifferentiated state, and multipotency demonstrated by clonal analysis. We analyzed the differentiation seven days after the transfer of the cells in different culture media. In the absence of serum, EGF led to the expression of the neuronal marker β-tubulin-III, and the acquisition of neuronal morphology in 15% of the cells. Analysis of cell proliferation by bromodeoxyuridine incorporation revealed that EGF mainly induced the formation of neurons without stimulating massively cell cycle progression. Moreover, a pulse of 2h EGF stimulation was sufficient to induce neuronal differentiation. Some neurons were committed to the retinal ganglion cell (RGC) phenotype, as revealed by the expression of retinal ganglion markers (Ath5, Brn3b and melanopsin), and in few cases to other retinal phenotypes (photoreceptors (PRs) and bipolar cells). We confirmed that the late RSCs were not restricted over-time and conserved multipotentcy characteristics by generating retinal phenotypes that usually appear at early (RGC) or late (PRs) developmental stages. Our results show that EGF is not only a factor controlling glial development, as previously shown, but also a potent differentiation factor for retinal neurons, at least in vitro. On the other hand, we wanted to find out if the adult human eye contains retina stem cells. The eye of some fishes and amphibians continues to grow during adulthood due to the persistent activity of retinal stem cells (RSCs). In fish, the RSCs are located in the ciliary margin zone (CMZ) at the periphery of the retina. Although, the adult mammalian eye does not grow during adult life, several groups have shown that the adult mouse eye contains retinal stem cells in the homologous zone (i.e. the ciliary margin), in the pigmented epithelium and not in the neuroretina. These RSCs meet some criteria of stem cells. We identified and characterized the human retinal stem cells. We showed that they posses the same features as their rodent counterpart i.e. they self-renew, expand and differentiate into retinal neurons in vitro and in vivo (indicated by immunostaining and microarray analysis). Moreover, they can be greatly expanded while conserving their sternness potential as revealed by the gene expression profile analysis (microarray approach). They also expressed genes common to various stem cells: nucleostemin, nestin, Bmil , Notch2, ABCG2, c-kit and its ligand, as well as cyclin D3 which acts downstream of c-kit. Furthermore, Bmil and Oct-4 were required for RSC proliferation reinforcing their stem cell identity. Our data indicate that the mice postnatal neuroretina and the adult pigmented epithelium of adult human ciliary margin contain retinal stem cells. We developed a system to easily expand and culture RSCs that can be used to investigate the retinogenesis. For example, it can help to screen drugs or factors involved, for instance, in the survival or generation of retinal cells. This could help to dissect genes or factors involved in the restriction or specification of retinal cell fate. In Western countries, retinitis pigmentosa (RP) affects 1 out of 3'500 individuals and age-related macula degeneration (AMD) strikes 1 % to 3% of the population over 60. In vitro generation of retinal cells is thus a promising tool to provide an unlimited cell source for cellular transplantation studies in the retina.

DSM-5: a collection of psychiatrist views on the changes, controversies, and future directions.

The recent release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) by the American Psychiatric Association has led to much debate. For this forum article, we asked BMC Medicine Editorial Board members who are experts in the field of psychiatry to discuss their personal views on how the changes in DSM-5 might affect clinical practice in their specific areas of psychiatric medicine. This article discusses the influence the DSM-5 may have on the diagnosis and treatment of autism, trauma-related and stressor-related disorders, obsessive-compulsive and related disorders, mood disorders (including major depression and bipolar disorders), and schizophrenia spectrum disorders.