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BACKGROUND: Hypothetico-deductive reasoning used by novice nurses could limit their ability to explain a presenting care situation in its entirety. Hence, scholars recommend the use of abductive reasoning as an alternative approach. PURPOSE: This study explored the effects of abductive reasoning training on baccalaureate nursing students' hypothesis generation abilities. METHOD: Through a pretest-posttest study, we delivered educational training on abductive reasoning and examined hypothesis accuracy, expertise, and breadth. Participants generated scenario-specific hypotheses before and after the training. Academic content experts validated the scenarios, and 2 independent raters scored participants' hypotheses. RESULTS: Twenty first- and second-year nursing students participated in this pilot study. Posttest scores showed a significant improvement in participants' hypothesis generation abilities: accuracy (P < .001), expertise (P < .001), and breadth (P = .006). CONCLUSION: Abductive reasoning training in nursing education may improve students' hypothesis generation abilities.
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Educación en Enfermería , Estudiantes de Enfermería , Competencia Clínica , Razonamiento Clínico , Humanos , Proyectos Piloto , Estudiantes de Enfermería/psicologíaRESUMEN
Epidermal keratinocytes migrate through the epidermis up to the granular layer where, on terminal differentiation, they progressively lose organelles and convert into anucleate cells or corneocytes. Our report explores the role of autophagy in ensuring epidermal function providing the first comprehensive profile of autophagy marker expression in developing epidermis. We show that autophagy is constitutively active in the epidermal granular layer where by electron microscopy we identified double-membrane autophagosomes. We demonstrate that differentiating keratinocytes undergo a selective form of nucleophagy characterized by accumulation of microtubule-associated protein light chain 3/lysosomal-associated membrane protein 2/p62 positive autolysosomes. These perinuclear vesicles displayed positivity for histone interacting protein, heterochromatin protein 1α, and localize in proximity with Lamin A and B1 accumulation, whereas in newborn mice and adult human skin, we report LC3 puncta coincident with misshaped nuclei within the granular layer. This process relies on autophagy integrity as confirmed by lack of nucleophagy in differentiating keratinocytes depleted from WD repeat domain phosphoinositide interacting 1 or Unc-51 like autophagy activating kinase 1. Final validation into a skin disease model showed that impaired autophagy contributes to the pathogenesis of psoriasis. Lack of LC3 expression in psoriatic skin lesions correlates with parakeratosis and deregulated expression or location of most of the autophagic markers. Our findings may have implications and improve treatment options for patients with epidermal barrier defects.
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Autofagia , Núcleo Celular/metabolismo , Epidermis/fisiología , Queratinocitos/citología , Proteínas Asociadas a Microtúbulos/metabolismo , Animales , Animales Recién Nacidos , Diferenciación Celular , Células Cultivadas , Epidermis/embriología , Humanos , Lamina Tipo A/metabolismo , Lamina Tipo B/metabolismo , Lisosomas/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina , Ratones , Complejos Multiproteicos/metabolismo , Fagosomas/metabolismo , Psoriasis/patología , Piel/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
The protein iASPP (encoded by PPP1R13L) is an evolutionarily conserved p53 inhibitor, the expression of which is often upregulated in human cancers. We have recently shown that iASPP is a crucial regulator of epidermal homeostasis. Here, we report that iASPP also acts as autophagy inhibitor in keratinocytes. Our data show that depletion of iASPP protects keratinocytes from apoptosis by modulating the expression of Noxa (also known as PMAIP1). In our model, iASPP expression can affect the fission-fusion cycle, mass and shape of mitochondria. iASPP-silenced keratinocytes display disorganization of cytosolic compartments and increased metabolic stress caused by deregulation of mTORC1 signaling. Moreover, increased levels of lipidated LC3 protein confirmed the activation of autophagy in iASPP-depleted cells. We have identified a novel mechanism modulating autophagy in keratinocytes that relies upon iASPP expression specifically reducing the interaction of Atg5-Atg12 with Atg16L1, an interaction that is essential for autophagosome formation or maturation. Using organotypic culture, we further explored the link between autophagy and differentiation, and we showed that impairing autophagy affects epidermal terminal differentiation. Our data provide an alternative mechanism to explain how epithelial integrity is maintained against environmental stressors and might also improve the understanding of the etiology of skin diseases that are characterized by defects in differentiation and DNA damage responses.
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Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Queratinocitos/citología , Queratinocitos/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Apoptosis/fisiología , Autofagia/fisiología , Proteína 5 Relacionada con la Autofagia , Proteínas Relacionadas con la Autofagia , Proteínas Portadoras/metabolismo , Diferenciación Celular/fisiología , Células Epidérmicas , Epidermis/metabolismo , Humanos , Proteínas Asociadas a Microtúbulos/metabolismoRESUMEN
Anogenital malignancy has a significant association with high-risk mucosal alpha-human papillomaviruses (alpha-PV), particularly HPV 16 and 18 whereas extragenital SCC has been linked to the presence of cutaneous beta and gamma-HPV types. Vulval skin may be colonised by both mucosal and cutaneous (beta-, mu-, nu- and gamma-) PV types, but there are few systematic studies investigating their presence and their relative contributions to vulval malignancy. Dysregulation of AKT, a serine/threonine kinase, plays a significant role in several cancers. Mucosal HPV types can increase AKT phosphorylation and activity whereas cutaneous HPV types down-regulate AKT1 expression, probably to weaken the cornified envelope to promote viral release. We assessed the presence of mucosal and cutaneous HPV in vulval malignancy and its relationship to AKT1 expression in order to establish the corresponding HPV and AKT1 profile of normal vulval skin, vulval intraepithelial neoplasia (VIN) and vulval squamous cell carcinoma (vSCC). We show that HPV16 is the principle HPV type present in VIN, there were few detectable beta types present and AKT1 loss was not associated with the presence of these cutaneous HPV. We show that HPV16 early gene expression reduced AKT1 expression in transgenic mouse epidermis. AKT1 loss in our VIN cohort correlated with presence of high copy number, episomal HPV16. Maintained AKT1 expression correlated with low copy number, an increased frequency of integration and increased HPV16E7 expression, a finding we replicated in another untyped cohort of vSCC. Since expression of E7 reflects tumour progression, these findings suggest that AKT1 loss associated with episomal HPV16 may have positive prognostic implications in vulval malignancy.
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Carcinoma de Células Escamosas/metabolismo , Papillomavirus Humano 16/metabolismo , Infecciones por Papillomavirus/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Neoplasias de la Vulva/metabolismo , Animales , Carcinoma de Células Escamosas/virología , Estudios de Cohortes , ADN Viral/genética , Progresión de la Enfermedad , Femenino , Dosificación de Gen , Interacciones Huésped-Patógeno , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/fisiología , Humanos , Inmunohistoquímica , Ratones , Ratones Transgénicos , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/metabolismo , Infecciones por Papillomavirus/virología , Reacción en Cadena de la Polimerasa , Neoplasias del Cuello Uterino/virología , Vulva/metabolismo , Vulva/patología , Vulva/virología , Neoplasias de la Vulva/virologíaRESUMEN
In Qatar, cardiovascular diseases are the leading cause of death. Studies show that depression is associated with an increased morbidity and mortality among cardiovascular patients. Thus, early detection of, and intervention for, depression among cardiovascular patients can reduce cardiovascular morbidity and mortality, and save health care costs. To date there is no study in the Gulf region exploring depression among cardiovascular patients. The goals of our three-phase research program are to (1) understand the mental health issues, specifically depression, as experienced by cardiovascular patients living in the State of Qatar; (2) identify and implement strategies that would prevent depression and assist patients to deal with depression; and (3) evaluate, facilitate, and sustain strategies that are effective at reducing depression and foster its treatment among cardiovascular patients. This paper describe phase I of the research program. Using both quantitative and qualitative research methodologies, we will investigate (1) the prevalence and severity of depression among patients who have confirmed diagnosis of cardiovascular diseases (2) how contextual factors such as social, cultural, and economic factors contribute to the risk of depression and its management among cardiovascular patients, and (3) formulate effective intervention strategies that are expected to increase awareness, prevention of and treatment for depression among cardiovascular patients, thus reducing cardiovascular diseases morbidity and mortality in Qatar.
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Filaggrin variants are well-established risk factors for atopic eczema (AE). Recent studies suggest additional epidermal differentiation complex (EDC) gene associations with AE. In this issue, Marenholz and colleagues confirm this prediction and show that a small proline-rich protein 3 (SPRR3) variant confers susceptibility to AE. This finding suggests that further genetic and functional characterization of SPRR3 should be performed in patients with AE.
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Proteínas Ricas en Prolina del Estrato Córneo/genética , Dermatitis Atópica/genética , Epidermis/fisiología , Predisposición Genética a la Enfermedad/genética , Dermatitis Atópica/epidemiología , Dermatitis Atópica/patología , Proteínas Filagrina , Predisposición Genética a la Enfermedad/epidemiología , Humanos , Factores de RiesgoRESUMEN
The epidermal barrier varies over the body surface to accommodate regional environmental stresses. Regional skin barrier variation is produced by site-dependent epidermal differentiation from common keratinocyte precursors and often manifests as site-specific skin disease or irritation. There is strong evidence for body-site-dependent dermal programming of epidermal differentiation in which the epidermis responds by altering expression of key barrier proteins, but the underlying mechanisms have not been defined. The LCE multigene cluster encodes barrier proteins that are differentially expressed over the body surface, and perturbation of LCE cluster expression is linked to the common regional skin disease psoriasis. LCE subclusters comprise genes expressed variably in either external barrier-forming epithelia (e.g. skin) or in internal epithelia with less stringent barriers (e.g. tongue). We demonstrate here that a complex of TALE homeobox transcription factors PBX1, PBX2 and Pknox (homologues of Drosophila Extradenticle and Homothorax) preferentially regulate external rather than internal LCE gene expression, competitively binding with SP1 and SP3. Perturbation of TALE protein expression in stratified squamous epithelia in mice produces external but not internal barrier abnormalities. We conclude that epidermal barrier genes, such as the LCE multigene cluster, are regulated by TALE homeodomain transcription factors to produce regional epidermal barriers.
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Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Proteínas Represoras/metabolismo , Fenómenos Fisiológicos de la Piel/genética , Animales , Secuencia de Bases , Diferenciación Celular/genética , Diferenciación Celular/fisiología , Proteínas Ricas en Prolina del Estrato Córneo/genética , Células Epidérmicas , Epidermis/metabolismo , Humanos , Queratinocitos/metabolismo , Ratones , Ratones Transgénicos , Regiones Promotoras Genéticas , Proteínas Represoras/genética , Piel/citología , Piel/metabolismoRESUMEN
BACKGROUND: Research has shown strong links between parenting and child psychopathology. The moderating role of child gender is of particular interest, due to gender differences in socialization history and in the prevalence of psychiatric disorders. Currently there is little agreement on how gender moderates the relationship between parenting and child psychopathology. This study attempts to address this lack of consensus by drawing upon two theories (self-salience vs. gender stereotyped misbehaviour) to determine how child gender moderates the role of parenting, if at all. METHODS: Using generalized estimating equations (GEE) associations between three parenting dimensions (hostile-ineffective parenting, parental consistency, and positive interaction) were examined in relationship to child externalizing (physical aggression, indirect aggression, and hyperactivity-inattention) and internalizing (emotional disorder-anxiety) dimensions of psychopathology. A sample 4 and 5 year olds from the National Longitudinal Survey of Children and Youth (NLSCY) were selected for analysis and followed over 6 years (N = 1214). Two models with main effects (Model 1) and main effects plus interactions (Model 2) were tested. RESULTS: No child gender-by-parenting interactions were observed for child physical aggression and indirect aggression. The association between hostile-ineffective parenting and child hyperactivity was stronger for girls, though this effect did not reach conventional levels of statistical significance (p = .059). The associations between parenting and child emotional disorder did vary as a function of gender, where influences of parental consistency and positive interaction were stronger for boys. DISCUSSION: Despite the presence of a few significant interaction effects, hypotheses were not supported for either theory (i.e. self-salience or gender stereotyped misbehaviour). We believe that the inconsistencies in the literature regarding child gender-by-parenting interactions is due to the reliance on gender as an indicator of a different variable which is intended to explain the interactions. This may be problematic because there is likely within-gender and between-sample variability in such constructs. Future research should consider measuring and modelling variables that are assumed to explain such interactions when conducting gender-by-parenting research.
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BACKGROUND: Lone-mother led families are at increased risk of psychosocial disadvantage, social isolation and mental health morbidity. Community-based programs are more accessible for families seeking assistance. We examine the experiences of eight lone mothers participating in a larger randomized controlled trial (RCT) of a community-based education/support group program using mixed methods. METHODS: A purposeful sample of eight mothers participating in the intervention arm of an RCT of community-based support/education groups was selected for the qualitative study. Individual interviews asked mothers about themselves and their relationships with their children before and after the group. Interviews were taped, transcribed and content analysis was used to code and interpret the data. Quantitative data collected in the RCT were used to describe these mothers. RESULTS: Mothers participating in the RCT and qualitative study experienced multiple difficulties, including financial and mood problems. These mothers reported that before participating in the group, they had shared experiences of social isolation, stigma, a sense of failure, poor relationships with their children and difficulties with financial management. After the group, mothers identified improved self-esteem, support from other mothers, improved parenting skills and improved communication with their children as outcomes of group participation. CONCLUSIONS: The qualitative data revealed mothers' perceptions of specific areas that improved by participating in the group. The utility of complementary information provided by qualitative and quantitative methods in understanding program impact, as well as the need for broader assistance is noted.
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Madres/psicología , Grupos de Autoayuda , Padres Solteros/psicología , Adulto , Femenino , Financiación Personal , Humanos , Entrevistas como Asunto , Trastornos del Humor , Relaciones Madre-Hijo , Investigación Cualitativa , Autoimagen , Aislamiento Social , Adulto JovenRESUMEN
The skin as a surface organ is uniquely accessible for whole embryo/foetal analyses of developmental changes, such as gene induction, protein expression, formation of epidermal-derived appendages such as hair follicles and formation of the protective barrier. Such analyses have emphasised the heterogeneous nature of skin development, perhaps not surprisingly because epidermal development is programmed by heterogeneous underlying mesenchyme. It is necessary to account for this heterogeneity by precisely matching body sites when correlating sequential events during development, for example, the activation of gene expression, or comparing wild-type with mutant/knockout animals. In this chapter protocols designed to assay whole-mount in situ hybridisation and whole-mount barrier formation are presented. Formation of the protective barrier is the endpoint of epidermal terminal differentiation and defects in this process are reflected in failure, acceleration, or delay in barrier formation. Hence, these latter assays are of particular value as a rapid initial assay for epidermal developmental defects in genetically modified mice.
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Epidermis/embriología , Hibridación in Situ/métodos , ARN/análisis , Animales , Tipificación del Cuerpo/genética , Embrión de Mamíferos/metabolismo , Epidermis/metabolismo , Ratones , Piel/metabolismoRESUMEN
Acquisition of epidermal barrier function occurs late in mouse gestation. Several days before birth a wave of barrier acquisition sweeps across murine fetal skin, converging on dorsal and ventral midlines. We investigated the molecular pathways active during epidermal barrier formation. Akt signaling increased as the barrier wave crossed epidermis and Jun was transiently dephosphorylated. Inhibitor experiments on embryonic explants showed that the dephosphorylation of Jun was dependent on both Akt and protein phosphatase 2A (Pp2a). Inhibition of Pp2a and Akt signaling also caused defects in epidermal barrier formation. These data are compatible with a model for developmental barrier acquisition mediated by Pp2a regulation of Jun dephosphorylation, downstream of Akt signaling. Support for this model was provided by siRNA-mediated knockdown of Ppp2r2a (Pr55alpha or B55alpha), a regulatory subunit of Pp2a expressed in an Akt-dependent manner in epidermis during barrier formation. Ppp2r2a reduction caused significant increase in Jun phosphorylation and interfered with the acquisition of barrier function, with barrier acquisition being restored by inhibition of Jun phosphorylation. Our data provide strong evidence that Ppp2r2a is a regulatory subunit of Pp2a that targets this phosphatase to Jun, and that Pp2a action is necessary for barrier formation. We therefore describe a novel Akt-dependent Pp2a activity that acts at least partly through Jun to affect initial barrier formation during late embryonic epidermal development.
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Epidermis/embriología , Epidermis/enzimología , Proteína Fosfatasa 2/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Animales , Diferenciación Celular , Células Cultivadas , Células Epidérmicas , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Queratinocitos/enzimología , Ratones , Fosforilación , Proteína Fosfatasa 2/genética , ARN Interferente Pequeño/genética , Ratas , Técnicas de Cultivo de TejidosRESUMEN
Epithelial tumorigenesis has been linked to AKT up-regulation. Human papillomaviruses (HPV) cause anogenital cancers and anogenital HPV infection up-regulates AKT activity. Mounting evidence points to a role for cutaneous HPVs as etiologic factors in skin tumorigenesis. High-risk cutaneous beta HPVs have been linked to carcinogenesis in immunosuppressed patients, and high-risk cutaneous HPV8 genes enhance tumorigenesis in transgenic mice. We find that, in contrast to anogenital HPVs, cutaneous HPV8 early genes down-regulate epidermal AKT activity by down-regulating AKT1 isoform levels. This down-regulation occurs before papilloma formation or tumorigenesis and leads to cutaneous differentiation changes that may weaken the epidermal squame for viral release. We find that, in viral warts (papillomas) and HPV gene-induced epidermal tumors, AKT activity can be activated focally by up-regulation and phosphorylation of the AKT2 isoform. In squamous cell carcinomas (SCC), AKT1 down-regulation is also common, consistent with a viral influence, whereas AKT2 up-regulation is widespread. Activation of up-regulated AKT2 by serine phosphorylation associates with high-grade tumors. Our data suggest that AKT2 up-regulation is characteristic of SCC and that coincident AKT2 activation through serine phosphorylation correlates with malignancy. These findings highlight differences between the effects of anogenital and cutaneous HPV on epithelial AKT activity and furthermore show that AKT isoforms can behave differently during epidermal tumorigenesis. These findings also suggest AKT2 as a possible therapeutic tumor target in SCC.
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Carcinoma de Células Escamosas/genética , Proteínas Oncogénicas Virales/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Neoplasias Cutáneas/genética , Transactivadores/metabolismo , Alphapapillomavirus/genética , Animales , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/etiología , Células Cultivadas , Expresión Génica , Genes Virales , Humanos , Queratinocitos/citología , Queratinocitos/virología , Ratones , Técnicas de Cultivo de Órganos , Fosforilación , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/etiologíaRESUMEN
AKT activity has been reported in the epidermis associated with keratinocyte survival and differentiation. We show in developing skin that Akt activity associates first with post-proliferative, para-basal keratinocytes and later with terminally differentiated keratinocytes that are forming the fetal stratum corneum. In adult epidermis the dominant Akt activity is in these highly differentiated granular keratinocytes, involved in stratum corneum assembly. Stratum corneum is crucial for protective barrier activity, and its formation involves complex and poorly understood processes such as nuclear dissolution, keratin filament aggregation, and assembly of a multiprotein cell cornified envelope. A key protein in these processes is filaggrin. We show that one target of Akt in granular keratinocytes is HspB1 (heat shock protein 27). Loss of epidermal HspB1 caused hyperkeratinization and misprocessing of filaggrin. Akt-mediated HspB1 phosphorylation promotes a transient interaction with filaggrin and intracellular redistribution of HspB1. This is the first demonstration of a specific interaction between HspB1 and a stratum corneum protein and indicates that HspB1 has chaperone activity during stratum corneum formation. This work demonstrates a new role for Akt in epidermis.
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Diferenciación Celular , Epidermis/metabolismo , Proteínas de Choque Térmico/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Células Epidérmicas , Proteínas Filagrina , Proteínas de Choque Térmico HSP27 , Proteínas de Choque Térmico/química , Proteínas de Filamentos Intermediarios/metabolismo , Ratones , Ratones Noqueados , Fosforilación , Serina/metabolismoRESUMEN
A randomized control trial completed in the Hamilton-Wentworth and Halton regions of Ontario, Canada, was created to assess the effects and expense of age-appropriate provider-initiated and subsidized versus self-directed and self-financed methods of recreation. Upon completion, this study proved that the annual per-person expenditure for the subsidized, quality recreation paid for itself by children's lower use of healthcare and social services. The children within the subsidized recreation group had lower use of physician, physiotherapy, probation, children's aid society, social work, psychologist and services in comparison with those in the non-subsidized group. The subsidized group also proved to be beneficial for the parents as well. The use of health and social services, by the parents in the subsidized group, was also decreased in comparison with those of the self-financed group. This group also proved to have improvement of the global socioeconomic status, with a 10% greater exit from the social assistance program within 1 year.
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Servicios de Salud del Niño/estadística & datos numéricos , Gastos en Salud/estadística & datos numéricos , Trastornos Mentales/terapia , Asistencia Pública/economía , Recreación/economía , Adolescente , Niño , Preescolar , Análisis Costo-Beneficio , Estudios de Seguimiento , Humanos , Ontario , PadresRESUMEN
Haploinsufficiency of the ATP2A2 gene product, SERCA2, underlies most cases of Darier's disease. Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase isoform 2 (SERCA2) is an intracellular Ca2+ pump that replenishes ER Ca2+, and it seems likely that the disease manifests in stress-induced lesions because SERCA levels become limiting as extra demands are made on the pump in times of stress. However, Müller and colleagues (2006) present a radical new proposal invoking somatic mutation as the basis for Darier lesions. Using a novel animal model for depleted keratinocyte SERCA-gated Ca2+ stores, the authors show that keratinocytes from Darier-like lesions retain their distinctive phenotype after culture, suggesting heritable defects. Mechanistically linking stress, calcium levels, mutation, and disease pathogenesis is complicated, and the proposal is likely to be controversial. However, recent reports of age- and stress-dependent tumor formation in the mouse model for SERCA2 haploinsufficiency (ATP2A2 heterozygous mouse) support the proposal that deficiency in SERCA-gated ER Ca2+ replenishment may be linked to mutation accumulation.
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ATPasas Transportadoras de Calcio/genética , Enfermedad de Darier/genética , Enfermedad de Darier/patología , Mutagénesis , Animales , Perros , Humanos , Mutación , ATPasas Transportadoras de Calcio del Retículo SarcoplásmicoRESUMEN
OBJECTIVE: This study examined differences in children's behavior and expenditures for health and social services used when their parents with dysthymia did or did not respond to antidepressant therapy. METHOD: Children ages 4 to 16 years of consenting parents enrolled in a treatment trial for dysthymia who did and did not respond to treatment were compared at baseline and 24 months. The responder was a parent with at least a 40% reduction in his or her baseline depressive symptoms using the Montgomery Asberg Depression Rating Scale. Children's behavior was measured using the Child Behavior Checklist, and expenditures for health and social services use was measured in Canadian dollars using the Health and Social Service Utilization Questionnaire. RESULTS: Children of parents with dysthymia who responded to treatment had significantly greater reductions in emotional symptoms at 2-year follow-up than children of nonresponders, along with an economically important (not statistically significant) reduction in expenditures for health and social services use. CONCLUSIONS: Reductions in parental symptoms of dysthymia may be associated with reductions in childhood behavioral problems and in expenditures for the child's use of services.
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Trastornos de la Conducta Infantil/epidemiología , Servicios de Salud del Niño/economía , Hijo de Padres Discapacitados/psicología , Trastorno Distímico/tratamiento farmacológico , Gastos en Salud , Servicio Social/economía , Adolescente , Adulto , Análisis de Varianza , Estudios de Casos y Controles , Niño , Trastornos de la Conducta Infantil/economía , Preescolar , Trastorno Distímico/psicología , Femenino , Estudios de Seguimiento , Humanos , Modelos Logísticos , Masculino , Ontario/epidemiologíaRESUMEN
The late cornified envelope (LCE) gene cluster within the epidermal differentiation complex on human chromosome one (mouse chromosome three) contains multiple conserved genes encoding stratum-corneum proteins. Within the LCE cluster, genes form "groups" based on chromosomal position and protein homology. We link a recently accepted nomenclature for the LCE cluster (formerly XP5, small proline-rich-like, late-envelope protein genes) to gene structure, groupings, and chromosomal organization, and carry out a pan-cluster quantitative expression analysis in a variety of tissues and environmental conditions. This analysis shows that (i) the cluster organizes into two "skin" expressing groups and a third group with low-level, tissue-specific expression patterns in all barrier-forming epithelia tested, including internal epithelia; (ii) LCE genes respond "group-wise" to environmental stimuli such as calcium levels and ultraviolet (UV) light, highlighting the functional significance of groups; (iii) in response to UV stimulation there is massive upregulation of a single, normally quiescent, non-skin LCE gene; and (iv) heterogeneity occurs between individuals with one individual lacking expression of an LCE skin gene without overt skin disease, suggesting LCE genes affect subtle attributes of skin function. This quantitative and pan-cluster expression analysis suggests that LCE groups have distinct functions and that within groups regulatory diversification permits specific responsiveness to environmental challenge.