BackgroundBreast cancer is the most common cancer in women. Among the survivors, depression is one of the most common psychiatric comorbidities. This paper reports the point prevalence of major depressive disorder among breast cancer patients and the association between family support and major depressive disorder.MethodsClinical data were collected from a breast cancer clinic of a general hospital in central Taiwan. Participants included 300 patients who were older than 18 years and diagnosed with breast cancer. Among these individuals, we used Mini International Neuropsychiatric Interview (a structural diagnostic tool for psychiatric disorders) to ascertain if they had major depressive disorder. We also used the Family Adaptability, Partnership, Growth, Affection, and Resolve score to assess the family support.ResultsThe point prevalence of major depressive disorder among breast cancer patients was 8.33%, and this was positively associated with insomnia, psychiatric family history, pain severity, and radiotherapy and negatively associated with menopause, cancer duration, hormone therapy, and family support. Family support (adjusted odds ratio =0.87, 95% CI: 0.78–0.98) was found to be an associated factor for major depressive disorder in breast cancer patients after controlling for potential risk factors.ConclusionMajor depressive disorder is a common comorbidity among breast cancer patients. Family support is an important associated factor for these patients. Health care professionals should evaluate mood problems and family support while treating these patients.

Health care providers should make use of community-oriented intervention programmes that aim to strengthen psychosocial functioning. Particularly, programmes that enhance health status and mutuality should be identified and developed for both individuals with schizophrenia and their families.

Huntington’s disease (HD) is an autosomal-dominant brain disorder caused by mutant huntingtin (mHtt). Although the detailed mechanisms remain unclear, the mutational expansion of polyglutamine in mHtt is proposed to induce protein aggregates and neuronal toxicity. Previous studies have shown that the decreased insulin sensitivity is closely related to mHtt-associated impairments in HD patients. However, how mHtt interferes with insulin signaling in neurons is still unknown. In the present study, we used a HD cell model to demonstrate that the miR-302 cluster, an embryonic stem cell-specific polycistronic miRNA, is significantly downregulated in mHtt-Q74-overexpressing neuronal cells. On the contrary, restoration of miR-302 cluster was shown to attenuate mHtt-induced cytotoxicity by improving insulin sensitivity, leading to a reduction of mHtt aggregates through the enhancement of autophagy. In addition, miR-302 also promoted mitophagy and stimulated Sirt1/AMPK-PGC1α pathway thereby preserving mitochondrial function. Taken together, these results highlight the potential role of miR-302 cluster in neuronal cells, and provide a novel mechanism for mHtt-impaired insulin signaling in the pathogenesis of HD.

BackgroundClerkship provides a unique way of transferring the knowledge and skills gathered during medical school’s curriculum into real-ward clinical care environment. The annual program evaluation has indicated that the training of clerks in diagnostic and clinical reasoning skills needed to be enhanced. Recently, “clinical excellence” program have been promoted in our institution to augment the excellence in clinical care of new clerks. Current study aims to evaluate whether this pilot program improve the “clinical excellence” of new clerks.MethodsIn a pilot study, groups of new clerks in years 2013 and 2014 voluntarily attended either a small-group brainstorming course or a didactic classroom tutoring courses as part of their 3-month internal medicine clinical rotation block. A third group of new clerks did not join either of the above courses and this group served as the control group. Pre-block/post-block self-assessment and post-block 5-station mini-Objective Subjective Clinical Examinations (OSCEs) were used to evaluate the effectiveness of these two additional courses that trained diagnostic and clinical reasoning skills.ResultsOvertime, the percentages of new clerks that attended voluntarily either the small-group brainstorming or classroom tutoring courses were increased. Higher post-block self-assessed diagnostic and clinical reasoning skill scores were found among individuals who attended the small-group brainstorming courses compared to either the didactic group or the control group. In a corresponding manner, the small-group brainstorming group obtained higher summary OSCEdiag and OSCEreason scores than either the didactic group or control group. For all basic images/laboratory OSCE stations, the individual diagnostic skill (OSCEdiag) scores of the small-group brainstorming group were higher than those of the didactic group. By way of contrast, only the clinical reasoning skill (OSCEreason) scores of the basic electrocardiogram and complete blood count + biochemistry OSCE station of thesmall-group brainstorming group were higher than those of the didactic group. Among the small-group brainstorming group, clerks with higher cumulative learning hours (>30-h) had significant higher OSCEdiag and OSCEreason scores (>400) than those with less cumulative learning hours.ConclusionOur pilot study provides a successful example of the use of a small-group tutoring courses for augmenting the diagnostic and clinical reasoning skills of new clerks. The positive results obtained during the initial 2-year long pilot “clinical excellence” program have encouraged the formal implementation of this course as part of the clerkship curriculum.Electronic supplementary materialThe online version of this article (doi:10.1186/s12909-016-0843-6) contains supplementary material, which is available to authorized users.

Huntington’s disease (HD) is a progressive and fatal neurodegenerative disease caused by CAG repeat expansion in the coding region of huntingtin (HTT) protein. The accumulation of mutant HTT (mHTT) contributes to neurotoxicity by causing autophagy defects and oxidative stress that ultimately lead to neuronal death. Interestingly, epidemiologic studies have demonstrated that the prevalence of type-2 diabetes, a metabolic disease mainly caused by defective insulin signaling, is higher in patients with HD than in healthy controls. Although the precise mechanisms of mHTT-mediated toxicity remain unclear, the blockade of brain insulin signaling may initiate or exacerbate mHTT-induced neurodegeneration. In this study, we used an in vitro HD model to investigate whether neuronal insulin signaling is involved in mHTT-mediated neurotoxicity. Our results demonstrated that mHTT overexpression significantly impairs insulin signaling and causes apoptosis in neuronal cells. However, treatment with liraglutide, a GLP-1 analogue, markedly restores insulin sensitivity and enhances cell viability. This neuroprotective effect may be attributed to the contribution of the upregulated expression of genes associated with endogenous antioxidant pathways to oxidative stress reduction. In addition, liraglutide stimulates autophagy through AMPK activation, which attenuates the accumulation of HTT aggregates within neuronal cells. Our findings collectively suggest that liraglutide can rescue impaired insulin signaling caused by mHTT and that GLP-1 may potentially reduce mHTT-induced neurotoxicity in the pathogenesis of HD.

This raised the possibility that insulin resistance could be one of the causative factors of αSyn toxicity, and the strategies for insulin sensitization may have therapeutic potential for synucleinopathies including DLB.

Huntington's disease (HD) is a progressive and fatal neurodegenerative disease caused by CAG repeat expansion in the coding region of huntingtin (HTT) protein. The accumulation of mutant HTT (mHTT) contributes to neurotoxicity by causing autophagy defects and oxidative stress that ultimately lead to neuronal death. Interestingly, epidemiologic studies have demonstrated that the prevalence of type-2 diabetes, a metabolic disease mainly caused by defective insulin signaling, is higher in patients with HD than in healthy controls. Although the precise mechanisms of mHTT-mediated toxicity remain unclear, the blockade of brain insulin signaling may initiate or exacerbate mHTT-induced neurodegeneration. In this study, we used an in vitro HD model to investigate whether neuronal insulin signaling is involved in mHTT-mediated neurotoxicity. Our results demonstrated that mHTT overexpression significantly impairs insulin signaling and causes apoptosis in neuronal cells. However, treatment with liraglutide, a GLP-1 analogue, markedly restores insulin sensitivity and enhances cell viability. This neuroprotective effect may be attributed to the contribution of the upregulated expression of genes associated with endogenous antioxidant pathways to oxidative stress reduction. In addition, liraglutide stimulates autophagy through AMPK activation, which attenuates the accumulation of HTT aggregates within neuronal cells. Our findings collectively suggest that liraglutide can rescue impaired insulin signaling caused by mHTT and that GLP-1 may potentially reduce mHTT-induced neurotoxicity in the pathogenesis of HD.

Amyloid β (Aβ) is a peptide fragment of the amyloid precursor protein that triggers the progression of Alzheimer’s Disease (AD). It is believed that Aβ contributes to neurodegeneration in several ways, including mitochondria dysfunction, oxidative stress and brain insulin resistance. Therefore, protecting neurons from Aβ-induced neurotoxicity is an effective strategy for attenuating AD pathogenesis. Recently, applications of stem cell-based therapies have demonstrated the ability to reduce the progression and outcome of neurodegenerative diseases. Particularly, Nanog is recognized as a stem cell-related pluripotency factor that enhances self-renewing capacities and helps reduce the senescent phenotypes of aged neuronal cells. However, whether the upregulation of Nanog can be an effective approach to alleviate Aβ-induced neurotoxicity and senescence is not yet understood. In the present study, we transiently overexpressed Nanog—both in vitro and in vivo—and investigated the protective effects and underlying mechanisms against Aβ. We found that overexpression of Nanog is responsible for attenuating Aβ-triggered neuronal insulin resistance, which restores cell survival through reducing intracellular mitochondrial superoxide accumulation and cellular senescence. In addition, upregulation of Nanog expression appears to increase secretion of neurotrophic factors through activation of the Nrf2 antioxidant defense pathway. Furthermore, improvement of memory and learning were also observed in rat model of Aβ neurotoxicity mediated by upregulation of Nanog in the brain. Taken together, our study suggests a potential role for Nanog in attenuating the neurotoxic effects of Aβ, which in turn, suggests that strategies to enhance Nanog expression may be used as a novel intervention for reducing Aβ neurotoxicity in the AD brain.