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The Hippo signaling pathway is a master regulator of organ growth, tissue homeostasis, and tumorigenesis. The activity of the Hippo pathway is controlled by various upstream components, including Expanded (Ex), but the precise molecular mechanism of how Ex is regulated remains poorly understood. Here we identify Plenty of SH3s (POSH), an E3 ubiquitin ligase, as a key component of Hippo signaling in DrosophilaPOSH overexpression synergizes with loss of Kibra to induce overgrowth and up-regulation of Hippo pathway target genes. Furthermore, knockdown of POSH impedes dextran sulfate sodium-induced Yorkie-dependent intestinal stem cell renewal, suggesting a physiological role of POSH in modulating Hippo signaling. Mechanistically, POSH binds to the C-terminal of Ex and is essential for the Crumbs-induced ubiquitination and degradation of Ex. Our findings establish POSH as a crucial regulator that integrates the signal from the cell surface to negatively regulate Ex-mediated Hippo activation in Drosophila.
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Proteínas de Transporte/metabolismo , Proteínas do Citoesqueleto/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Ubiquitina/metabolismo , Animais , Proteínas de Transporte/genética , Proteínas do Citoesqueleto/genética , Sulfato de Dextrana , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Deleção de Genes , Genoma , Intestinos/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Ligação Proteica , Proteínas Serina-Treonina Quinases/genética , Proteólise , Transdução de Sinais , Células-Tronco/efeitos dos fármacos , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismoRESUMO
This paper examines the factors associated with the cultural phenomenon of bacha posh in Afghanistan (in which girls are dressed and raised as boys), which occurs against a background of rigid gender norms and the male-centric nature of Afghan families. Survey data were collected from 1463 women in two provinces of Afghanistan, Kabul and Nangarhar. The primary outcome is a nominal variable, derived from the question, 'Do you have any girl in your family who has been raised for any time as a boy?' Independent variables comprise women's socio-demographic characteristics, family composition, economic characteristics, patriarchal gender attitudes and perceptions of community patriarchal attitudes. Factors associated with bacha posh include women having fewer sons and more daughters, working in the past three months and having less patriarchal gender attitudes. That bacha posh is often driven by a large number of daughters in the family with a corresponding low number of sons suggests that bacha posh is a response to very contextual features of Afghan life, including the preference for sons. Bacha posh in the family is linked to less patriarchal gender norms and can be a way for girls and women to acquire education, mobility and engagement in income-generating activities.
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Educação Infantil/etnologia , Características da Família/etnologia , Identidade de Gênero , Núcleo Familiar/etnologia , Adolescente , Adulto , Afeganistão/etnologia , Criança , Feminino , Humanos , Pessoa de Meia-Idade , Fatores Socioeconômicos , Adulto JovemRESUMO
BACKGROUND: Apoptosis plays an important role in the regulation of healthy tissue growth and development as well as in controlling the maintenance of homeostasis in exercising muscles. During an intensive physical effort, the regulation of cell death by apoptosis results in the replacement of unaccustomed muscle cells by new cells that are better suited to exercise. The aim of this study was to determine the expression of two genes (SH3FR1 and SH3RF2) that control apoptosis in muscle tissues during training periods characterized by different intensities. The gene expression levels were estimated using real-time PCR method in skeletal muscle biopsies collected from 15 Arabian horses (untrained, after an intense gallop phase, and at the end of the racing season). An association study was performed on 250 Arabian horses to assess the effect of the SH3RF2:c.796 T > C (p.Ser266Pro) variant on race performance traits in flat gallop-racing. RESULTS: A gene expression analysis confirmed a significant decrease (p < 0.01) in the anti-apoptotic SH3RF2 (POSHER) gene during training periods that differed in intensity. The highest SH3RF2 expression level was detected in the muscles of untrained horses, whereas the lowest expression was identified at the end of the racing season in horses that were fully adapted to the exercise. A non-significant decrease in SH3RF1 gene expression following the training periods was observed. Moreover, a serine substitution by proline at amino acid position 266 (CC genotype) was negatively associated with the probability of winning races, the number of races in which a horse occurred and the financial value of the prizes. Horses with the TT genotype achieved the highest financial benefits, both for total winnings and for winnings per race in which the horses participated. CONCLUSIONS: The present study showed the supposed regulation mechanism of exercise-induced apoptosis in horses at the molecular level. The identified SH3RF2: c.796 T > C missense variant was associated with selected racing performance traits, which is important information during the evaluation of horses' exercise predisposition. The association results and frequencies of the CT and TT genotypes suggest the possibility of using SH3RF2 variant in selection to improve the racing performance of Arabian horses.
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Proteínas Reguladoras de Apoptose/genética , Apoptose/genética , Cavalos/genética , Músculo Esquelético/metabolismo , Condicionamento Físico Animal/fisiologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Expressão Gênica , Genótipo , Cavalos/fisiologia , Aptidão Física/fisiologia , Polimorfismo de Nucleotídeo Único , Corrida/fisiologiaRESUMO
Serine/threonine kinase Akt is a downstream effector of the phosphoinositide 3-kinase pathway that is involved in many processes, including providing neuroprotection to stressed photoreceptor cells. Akt exists in three isoforms designated as Akt1, Akt2, and Akt3. All of these isoforms are expressed in the retina. We previously reported that Akt2 knockout mice were susceptible to light stress-induced photoreceptor degeneration, whereas Akt1 deletion had no effect on the retina. We hypothesized that the phenotype of Akt2 knockout mice may be due to the inactivation of specific substrate(s) in the retina. Yeast two-hybrid screening of a bovine retinal cDNA library with Akt2 identified a multidomain protein, POSH (plenty of SH3s), that acts as a scaffold for the JNK pathway of neuronal death. Our results suggest a stable interaction between Akt2 and POSH. Previous studies show that overexpression of POSH leads to cell death. The cell death that we observed in Akt2 knockout mice could be due to the absence of inactivation of POSH-mediated JNK signaling in the retina.
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Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Proteínas do Citoesqueleto/fisiologia , Proteínas do Olho/fisiologia , Sistema de Sinalização das MAP Quinases , Proteínas Proto-Oncogênicas c-akt/fisiologia , Retina/enzimologia , Ubiquitina-Proteína Ligases/fisiologia , Animais , Bovinos , DNA Complementar/genética , Proteínas do Olho/genética , Células HEK293 , Humanos , Camundongos , Camundongos Knockout , Fenótipo , Mapeamento de Interação de Proteínas , Isoformas de Proteínas/deficiência , Isoformas de Proteínas/genética , Isoformas de Proteínas/fisiologia , Proteínas Proto-Oncogênicas c-akt/deficiência , Proteínas Proto-Oncogênicas c-akt/genética , Técnicas do Sistema de Duplo-HíbridoRESUMO
Following increased interest in and use of new public management (NPM), greater regulation has been introduced into many Western health systems. Yet, the effects have revealed the negative aspects of NPM. Positive organizational scholars have argued that adversity can give rise to positive deviance. Yet as a form of noncompliance, positive deviance can be difficult to examine. This methodological article demonstrates how the combined methodologies of positive organizational scholarship in healthcare (POSH) and video reflexive ethnography (VRE) can help examine positive deviance. This study illustrates the methodological utility of POSH VRE to respectfully study the impact of NPM-inspired expectations on public health clinicians, positively reframe how clinicians constructively respond to and manage obstruction, and reveal the unintended effects of NPM-inspired expectations. As a participatory methodology, POSH VRE can promote trust between researchers and clinicians, thereby unveiling instances of positive deviance to NPM in healthcare.
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Processos Grupais , Inovação Organizacional , Administração em Saúde Pública , Projetos de Pesquisa , Gravação de Videoteipe , Antropologia Cultural , HumanosRESUMO
Background: Laryngeal cancer is a common advanced head and neck cancer. Surgery, radiation, chemotherapy, or a combination of these treatments are used to treat locally advanced laryngeal cancer. Total laryngectomy is generally preferred for T3-4 laryngeal cancers, despite being an invasive procedure. Post-surgical hypocalcemia is a known complication of neck compartment surgeries, and patients who have undergone laryngectomy are at a higher risk of developing hypoparathyroidism, leading to hypocalcemia. This study aims to investigate the prevalence and risk factors of hypocalcemia in individuals following laryngectomy. Method: This retrospective study examined 50 consecutive laryngectomy patients over eight years. Data on demographic characteristics, medical history, surgical details, pre-and post-operative calcium levels, neck dissection laterality, history of radiotherapy were collected. Hypocalcemia was defined as calcium levels < 8.5 mg/dl or corrected calcium < 8.5 mg/dl. Statistical analyses included paired t-tests, Wilcoxon signed-rank tests, and binary logistic regression using R studio. Results: The mean age of participants was 59 years, predominating males (94%) and habitual smokers (94%). Squamous cell carcinoma was the most prevalent (98%) pathological diagnosis, and various surgical techniques were employed. While initial comparisons showed no significant changes in calcium levels pre-and post-operatively, adjusting for albumin levels revealed a significant association. Logistic regression identified neck dissection, low pre-operative calcium, radiotherapy, and total thyroidectomy as significant predictors of post-operative hypocalcemia (p < 0.05). Conclusion: Surgical factors such as neck dissection and total thyroidectomy, alongside albumin levels, significantly impact postoperative hypocalcemia. These findings underscore the need for meticulous monitoring and potential preventive measures to manage calcium imbalance post-laryngectomy.
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BACKGROUND: The phrase "too posh to push" was coined over 14 years ago to describe maternal request for cesarean section in the absence of clinical indications. The phrase was readily taken up and used by the United Kingdom media despite limited evidence that many women request cesarean sections or have an aversion to vaginal birth. The objectives of this study were to explore the way in which the phrase was used; the context and themes associated with it. METHODS: To better understand the part the news media might play in public and health care professionals' perceptions, all articles using the phrase in eight UK national weekday newspapers from 1999 to 2011 (n = 335) were subjected to content analysis. RESULTS: Key themes have changed over the years but some themes, such as celebrity cesareans, the risks of cesarean section, and the rising cesarean rate, have remained. Four different definitions of the term "too posh to push" were identified. Levels of usage of these terms changed over time. Misinterpretation of the National Sentinel Cesarean Section Audit results and a tendency to confuse elective cesarean section with maternal request for a cesarean have suggested that more "too posh to push" cesareans occurred than is probably the case. CONCLUSION: The phrase seems to have become well established. It is likely that press handling of the topic has continued to contribute to the impression that cesarean purely for maternal request is common. The association with celebrity continues to fuel press interest in the topic.
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Cesárea/psicologia , Características Culturais , Procedimentos Cirúrgicos Eletivos/psicologia , Idioma , Jornais como Assunto/tendências , Aceitação pelo Paciente de Cuidados de Saúde , Cesárea/estatística & dados numéricos , Cesárea/tendências , Procedimentos Cirúrgicos Eletivos/estatística & dados numéricos , Procedimentos Cirúrgicos Eletivos/tendências , Feminino , Humanos , Gravidez , Fatores Socioeconômicos , Reino UnidoRESUMO
Post-surgical hypoparathyroidism (POSH) is a recognised complication of total thyroidectomy, leading to hypocalcaemia and its associated adverse effects. This retrospective study aimed to determine the incidence of POSH and identify perioperative predictors for its development. Data from patients who underwent total or completion thyroidectomy between January 2017 and July 2022 were retrospectively analysed. The incidence of POSH was assessed, and patients were categorised into transient or prolonged POSH at six months postoperatively. Potential predictors for POSH were investigated including gender, histological diagnosis, and preoperative thyroid function. A total of 133 adult patients were included in the study. The incidence of patients recovering from transient POSH within six months was 15%, and 5% had prolonged POSH beyond six months of surgery. Parathyroid hormone (PTH) levels normalised in 83% of prolonged POSH patients within 14-33 months, reducing the incidence of persistent POSH to 0.75%. Despite normal PTH levels, overall, 3% had persistent marginally low calcium levels (mean 2.11 mmol/L) in keeping with relative parathyroid insufficiency. Histological diagnosis of malignancy was the only significant risk factor for both transient and prolonged POSH (RR 2.95, CI 1.54 to 5.67, p = 0.001) in this cohort. Cautious capsular dissection during thyroidectomy and protection of the parathyroid glands and vascular supply produce a low incidence of POSH. Although the vast majority of patients with POSH recover after six months, hypocalcaemia may persist due to relative parathyroid insufficiency, requiring long-term calcium supplementation. Further research is needed to determine the best strategies for preventing and treating this condition.
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Hipocalcemia , Hipoparatireoidismo , Adulto , Humanos , Hipocalcemia/etiologia , Hipocalcemia/complicações , Tireoidectomia/efeitos adversos , Estudos Retrospectivos , Cálcio/uso terapêutico , Incidência , Hipoparatireoidismo/epidemiologia , Hipoparatireoidismo/etiologia , Hipoparatireoidismo/diagnóstico , Hormônio Paratireóideo , Glândulas Paratireoides , Complicações Pós-Operatórias/etiologiaRESUMO
Mutation or disruption of the Shank/ProSAP family of genes is a high risk factor for autism spectrum disorders (ASDs) and intellectual disability. N-methyl-D-aspartate glutamate receptor (NMDAR) dysfunction contributes to the development of autism-like behaviors. However, the molecular mechanism of Shank-mediated NMDAR modulation is still not clear. Here, we show that the scaffold protein plenty of SH3s (POSH) directly interacts with two other scaffold proteins, PSD95 and SHANK2/3, at excitatory synapses. In POSH conditional knockout (cKO) mice, normal synaptic clustering of NMDAR/PSD-95/SHANK complex is disrupted, accompanied by abnormal dendritic spine development and glutamatergic transmission in hippocampal neurons. POSH cKO mice display profound autism-like behaviors, including impairments in social interactions, social communication, repetitive behaviors, and deficits in learning and memory. Thus, POSH clusters at the postsynaptic density (PSD) with PSD-95 and SHANK2/3 and plays important roles in the signaling mechanisms of the NMDAR/PSD-95/POSH/SHANK complex as well as in spine development and brain function.
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Proteínas Adaptadoras de Transdução de Sinal , Ácido Aspártico , Proteínas do Citoesqueleto , Ácido Glutâmico , Receptores de N-Metil-D-Aspartato , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Ácido Aspártico/metabolismo , Proteínas do Citoesqueleto/metabolismo , Proteína 4 Homóloga a Disks-Large/metabolismo , Ácido Glutâmico/metabolismo , Camundongos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Sinapses/metabolismo , Transmissão SinápticaRESUMO
OBJECTIVES: In Afghanistan, strong son preferences render women with lower social capital. A practice was created to overcome this gender bias, known as bacha posh, which literally translates to 'dressing up as a boy'. This exploratory study aims to understand gender roles, identities, and experiences of Afghan women in order to understand why this cultural practice has arisen. DESIGN: Utilising a social constructivist approach, qualitative data was collected from Afghan migrant women in Melbourne, Australia, using semi-structured in-depth interviews (n=10) and a group discussion (n=1). The interviews were conducted in Dari, translated and transcribed to English and thematically analysed using NVivo 12. RESULTS: Key findings identified include the perception of an easy transition for girls to become and return from being bacha posh, community members knowing bacha posh are girls but concealing the truth to maintain family honour, and societal and familial son preferences playing a significant role in becoming bacha posh. Most participants perceived bacha posh to be an unnecessary practice, but understood that it may be an act of desperation forced upon them by the rigidity of Afghan society. CONCLUSIONS: This exploratory analysis makes an important contribution to understanding gender roles, identities and bacha posh in Afghanistan, and is the first qualitative study exploring how gender roles and norms in Afghanistan have led to the bacha posh phenomenon. Exploring how social and gender norms and son preferences contribute to the emergency of bacha posh is critical to understand challenges faced by this group, and how these power structures influence daily living.
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Mineral oil hydrocarbons (MOH) in milk powders, particularly in infant formulas, have been and continue to be a major concern to the public worldwide. These contaminants are likely derived from environmental pollution, manufacturing process and packaging materials. In this study, 23 Chinese commercial milk powder products packaged in four types of materials, i.e. metal cans, paper containers, paperboard boxes with internal bags, and aluminium foil-plastic bags, were collected and stored for 1 year. The total and surface MOH in these samples were detected and compared before and after storage to understand the MOH migration during storage, despite no mineral oil saturated hydrocarbons (MOAH) were detected. The contents of mineral oil saturated hydrocarbons (MOSH) and polyolefin oligomeric saturated hydrocarbons (POSH) in metal cans were the least among the four packages and changed little during storage, which suggested that little MOH migration occurred in metal material. Despite all the food contact materials in the other three packagings were the aluminium foil-plastic composite, the similar low migration occurred in the aluminium foil-plastic bags and internally contained composite bag(s) in paperboard boxes. However, both total and surface MOSH and POSH easily migrated from the paper-plastic-aluminium composite of paper containers during storage. These findings are helpful for the selection of packaging materials in manufacturing milk powder products or other foods.
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Contaminação de Alimentos/análise , Hidrocarbonetos/análise , Leite/química , Óleo Mineral/análise , Polienos/análise , Alumínio/química , Animais , Cromatografia Gasosa , Cromatografia Líquida de Alta Pressão , Embalagem de Alimentos , Inocuidade dos Alimentos , Humanos , Papel , Plásticos/químicaRESUMO
Recently, mineral oil hydrocarbons (MOH) in various foods have raised significant concern, especially for infants and young children due to their potential adverse health effects. Two fractions can be distinguished by certain analytical techniques, mineral oil saturated hydrocarbons (MOSH) and mineral oil aromatic hydrocarbons (MOAH). The toxicological profile of MOSH and MOAH differs greatly. The toxicity of MOSH is linked with long-term accumulation of some hydrocarbons. MOAH with three to seven, non- or simple-alkylated, aromatic rings may be mutagenic and carcinogenic. However, data on the occurrence of mineral oils in commercial complementary foods for infants and young children are lacking in China. In the present study, 100 commercial food samples were collected, including 26 pureed or paste canned foods, 21 high-protein ground cereal foods (rice flour), 25 raw cereal foods (noodles), and 28 cereal-based molar sticks and biscuits. The content of MOSH and MOAH in those samples was determined by optimised sample preparation methods combined with on-line high-performance liquid chromatography coupled with gas chromatography and flame ionisation detector (HPLC-GC-FID), with a limit of quantification of 0.5 mg/kg. The results indicated that there were no MOAH detected in any of the foods, but MOSH and polyolefin oligomeric saturated hydrocarbons (POSH) existed in most of the food samples, at <0.5-23.68 mg/kg. Moreover, the data and chromatograms of the MOSH and POSH also indicated that these contaminants were closely correlated to their ingredients and manufacturers. The current study provides basic data to understand MOH exposure and consequent health impact.
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Análise de Alimentos , Contaminação de Alimentos/análise , Hidrocarbonetos/análise , Óleo Mineral/química , Povo Asiático , Cromatografia Gasosa , Cromatografia Líquida de Alta Pressão , Humanos , Lactente , Recém-NascidoRESUMO
Mineral oil contaminants migrated from food contact materials have raised much concern in the past few decades. However, survey data of the occurrence of mineral oils in foods are only available for a limited variety of foods, which do not include the contaminants in Chinese milk powders. Thus, to conduct an analysis of mineral oils migrated into milk powder products from different packaging materials, 50 Chinese commercial samples (including 38 infant formulas), which were packaged in metal cans, paper containers, paper boxes and aluminium foil-plastic bags, were analysed. Mineral oil saturated hydrocarbons (MOSH), polyolefin oligomeric saturated hydrocarbons (POSH) and aromatic hydrocarbons (MOAH) migrated into those samples were extracted and quantitatively analysed by on-line liquid chromatography coupled with gas chromatography (LC-GC). The results indicated no surface MOAH was detected in any of the samples, while 33 samples contained MOSH/POSH with surface contents of 0.10 ~ 5.09 mg kg-1. Moreover, the amounts of those MOSH/POSH are closely related to packaging materials, among which the surface contamination values of products in metal cans were the lowest, followed by products in paper containers and boxes, and the values of samples in aluminium foil-plastic bags were the highest. In addition, the surface MOSH/POSH content exhibited a positive correlation with fat content in the samples due to their similar polarities.
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Laticínios/análise , Contaminação de Alimentos/análise , Hidrocarbonetos/análise , Fórmulas Infantis/análise , Leite/química , Óleo Mineral/análise , Animais , China , Humanos , Lactente , PósRESUMO
OBJECTIVE: Interdisciplinary management of elderly patients requiring spine surgery has been shown to improve short- and long-term outcomes. The aim of this study was to determine whether an interdisciplinary team approach mitigates use of intensive care unit (ICU) resources. METHODS: A unique comanagement model for elderly patients undergoing lumbar fusion surgery was implemented at a major academic medical center. The Peri-operative Optimization of Senior Health Program (POSH) was launched with the aim of improving outcomes in elderly patients (>65 years old) undergoing complex lumbar spine surgery. In this model, a geriatrician evaluates elderly patients preoperatively, comanages daily throughout hospital course, and coordinates multidisciplinary rehabilitation, along with the neurosurgical team. We retrospectively reviewed the first 100 cases after the initiation of the POSH protocol and compared them with the immediately preceding 25 cases to assess the rates of ICU transfer and independent predictors of ICU admission. RESULTS: A total of 125 patients undergoing lumbar decompression and fusion surgery were enrolled in this pilot program. Baseline characteristics and intraoperative variables, as well as number of fusion levels and duration of surgery, were similar between both cohorts. There was a significant difference in the use of ICU services (ICU admission rates) between both cohorts, with the non-POSH cohort having a 3-fold increase compared with the POSH cohort (P < 0.0001). In a multivariate analysis, lack of an interdisciplinary comanagement team approach was an independent predictor for ICU transfers in elderly patients undergoing corrective surgery (odds ratio 8.51, 95% confidence interval 2.972-24.37, P < 0.0001). CONCLUSIONS: Our study suggests that an interdisciplinary comanagement model between geriatrics and neurosurgery is independently associated with reduced use of critical care services.
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Cuidados Críticos/estatística & dados numéricos , Procedimentos Neurocirúrgicos/métodos , Equipe de Assistência ao Paciente , Cuidados Pós-Operatórios/estatística & dados numéricos , Escoliose/cirurgia , Idoso , Idoso de 80 Anos ou mais , Administração de Caso , Protocolos Clínicos , Estudos de Coortes , Descompressão Cirúrgica , Feminino , Geriatria , Humanos , Vértebras Lombares/cirurgia , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos , Escoliose/reabilitação , Fusão Vertebral , Resultado do TratamentoRESUMO
Total knee arthroplasty (TKA) is the most commonly performed inpatient surgical procedure within the USA and is estimated to reach 3.48 million procedures annually by 2030. As value-based care initiatives continue to focus on hospital readmission rates and patient satisfaction, it has become essential for health care providers to develop and implement a multidisciplinary approach to enhance TKA outcomes while minimizing unnecessary expenditures. Through this necessity, clinical care pathways have been developed to standardize, organize, and improve the quality and efficiency of patient care while simultaneously encouraging the collaboration among various medical care providers. Here, we review several systems based programs and specialty care practices that can be adopted into the standard orthopedic practice.
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OBJECTIVES: Plenty of SH3 (POSH) was originally found to be a key regulator of neuronal apoptosis, axon outgrowth, and neuronal migration. However, the role of POSH in epilepsy has not been reported. METHODS: We investigated the expression of POSH in patients with intractable temporal epilepsy (TLE) and in a kainic acid (KA)-induced mouse model, and then we performed behavioral, electrophysiological and biochemical analyses after the lentivirus (LV)-mediated knockdown or overexpression of POSH in the KA-induced model. RESULTS: POSH overexpression shortened the latency of seizure onset, increased the frequency of spontaneous recurrent seizures, and increased the frequency of electrical epileptic discharges, while POSH knockdown had contrasting effects. Whole-cell patch-clamp recordings confirmed that POSH overexpression and knockdown were associated with increased and decreased miniature excitatory postsynaptic currents (mEPSCs) and N-methyl-D-aspartate receptor (NMDAR)-mediated currents, respectively. Finally, co-immunoprecipitation showed that POSH and NMDA receptor subunit 1 (NMDAR1) precipitated with each other, and western blot analysis revealed that the surface expression of NMDAR1 was altered in the hippocampus of epileptic mice. CONCLUSION: These results show that POSH plays a critical role in the progression of epileptic seizures via NMDAR trafficking and suggest that the protein is a novel target for the treatment of human epilepsy.
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Epilepsia do Lobo Temporal/fisiopatologia , Terapia de Alvo Molecular , Receptores de N-Metil-D-Aspartato/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Adolescente , Adulto , Animais , Modelos Animais de Doenças , Epilepsia/genética , Epilepsia/fisiopatologia , Epilepsia/terapia , Epilepsia do Lobo Temporal/genética , Epilepsia do Lobo Temporal/terapia , Feminino , Técnicas de Silenciamento de Genes , Hipocampo/patologia , Humanos , Ácido Caínico/toxicidade , Lentivirus/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Técnicas de Patch-Clamp , Ubiquitina-Proteína Ligases/genética , Adulto JovemRESUMO
OBJECTIVE Geriatric patients undergoing lumbar spine surgery have unique needs due to the physiological changes of aging. They are at risk for adverse outcomes such as delirium, infection, and iatrogenic complications, and these complications, in turn, contribute to the risk of functional decline, nursing home admission, and death. Whether preoperative and perioperative comanagement by a geriatrician reduces the incidence of in-hospital complications and length of in-hospital stay after elective lumbar spine surgery remains unknown. METHODS A unique model of comanagement for elderly patients undergoing lumbar fusion surgery was implemented at a major academic medical center. The Perioperative Optimization of Senior Health (POSH) program was launched with the aim of improving outcomes in elderly patients (> 65 years old) undergoing complex lumbar spine surgery. In this model, a geriatrician evaluates elderly patients preoperatively, in addition to performing routine preoperative anesthesia surgical screening, and comanages them daily throughout the course of their hospital stay to manage medical comorbid conditions and coordinate multidisciplinary rehabilitation along with the neurosurgical team. The first 100 cases were retrospectively reviewed after initiation of the POSH protocol and compared with the immediately preceding 25 cases to assess the incidence of perioperative complications and clinical outcomes. RESULTS One hundred twenty-five patients undergoing lumbar decompression and fusion were enrolled in this pilot program. Baseline characteristics were similar between both cohorts. The mean length of in-hospital stay was 30% shorter in the POSH cohort (6.13 vs 8.72 days; p = 0.06). The mean duration of time between surgery and patient mobilization was significantly shorter in the POSH cohort compared with the non-POSH cohort (1.57 days vs 2.77 days; p = 0.02), and the number of steps ambulated on day of discharge was 2-fold higher in the POSH cohort (p = 0.04). Compared with the non-POSH cohort, the majority of patients in the POSH cohort were discharged to home (24% vs 54%; p = 0.01). CONCLUSIONS Geriatric comanagement reduces the incidence of postoperative complications, shortens the duration of in-hospital stay, and contributes to improved perioperative functional status in elderly patients undergoing elective spinal surgery for the correction of adult degenerative scoliosis.
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Tempo de Internação , Vértebras Lombares/cirurgia , Região Lombossacral/cirurgia , Procedimentos Neurocirúrgicos , Complicações Pós-Operatórias , Idoso , Idoso de 80 Anos ou mais , Descompressão Cirúrgica/métodos , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Humanos , Masculino , Procedimentos Neurocirúrgicos/métodos , Período Pós-Operatório , Estudos Prospectivos , Fusão Vertebral/métodosRESUMO
The recruitment of Graduates into the nursing profession is seen as advantageous in the academic literature. Conversely educated nurses are often portrayed in the media as "too posh to wash". We would argue these conflicting discourses have a negative effect on graduate entry nurse education. Graduate nursing students may be particularly susceptible to "Imposter Phenomenon" a concept that describes an "internal experience of intellectual phoniness" exhibited by individuals who appear successful to others, but internally feel incompetent. We would like to encourage debate through the presentation of a small set of pilot data that established that 70% of the participants had frequent to intense experiences of Imposter Phenomenon. Students experienced feelings of failure despite consistent high achievement. Our findings and the prevalent negative rhetoric surrounding highly educated student nurses raise concerns regarding the impact of the anti-intellectualism on the Graduate entry student's perception of self. Others may argue that this could simply be a 'natural' or expected level of anxiety in a time of transition that has no lasting impact. We debate this issue in relation to the existing literature to encourage critical dialogue.
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Atitude do Pessoal de Saúde , Educação de Pós-Graduação em Enfermagem , Ajustamento Social , Estudantes de Enfermagem/psicologia , Humanos , Seleção de Pessoal/métodosRESUMO
Many foods are contaminated by hydrocarbons of mineral oil or synthetic origin. High performance liquid chromatography on-line coupled with gas chromatography and flame ionization detection (HPLC-GC-FID) is a powerful tool for the quantitative determination, but it would often be desirable to obtain more information about the type of hydrocarbons in order to identify the source of the contamination and specify pertinent legislation. Comprehensive two-dimensional gas chromatography (GC×GC) is shown to produce plots distinguishing mineral oil saturated hydrocarbons (MOSH) from polymer oligomeric saturated hydrocarbons (POSH) and characterizing the degree of raffination of a mineral oil. The first dimension separation occurred on a phenyl methyl polysiloxane, the second on a dimethyl polysiloxane. Mass spectrometry (MS) was used for identification, FID for quantitative determination. This shows the substantial advances in chromatography to characterize complex hydrocarbon mixtures even as contaminants in food.