mTORC1-induced retinal progenitor cell overproliferation leads to accelerated mitotic aging and degeneration of descendent Müller glia.

Retinal progenitor cells (RPCs) divide in limited numbers to generate the cells comprising vertebrate retina. The molecular mechanism that leads RPC to the division limit, however, remains elusive. Here, we find that the hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) in an RPC subset by deletion of tuberous sclerosis complex 1 (Tsc1) makes the RPCs arrive at the division limit precociously and produce Müller glia (MG) that degenerate from senescence-associated cell death. We further show the hyperproliferation of Tsc1-deficient RPCs and the degeneration of MG in the mouse retina disappear by concomitant deletion of hypoxia-induced factor 1-alpha (Hif1a), which induces glycolytic gene expression to support mTORC1-induced RPC proliferation. Collectively, our results suggest that, by having mTORC1 constitutively active, an RPC divides and exhausts mitotic capacity faster than neighboring RPCs, and thus produces retinal cells that degenerate with aging-related changes.

Clinical and economic benefits associated with the use of powered and tissue-specific endoscopic staplers among the patients undergoing thoracoscopic lobectomy for lung cancer.

Background: Thoracoscopic lobectomy for lung cancer is a complex procedure where endoscopic staplers play a critical role in transecting the lung parenchyme, vasculature, and bronchus. This retrospective study was performed to investigate the economic benefits of powered and tissue-specific endoscopic staplers such as gripping surface technology (GST) and powered vascular stapler (PVS) compared to standard staplers.Methods: Two hundred and seventy-five patients who received a thoracoscopic lobectomy between 2008 and 2016 were included. Group 1 (n = 117) consisted of patients who received the operation with manual endoscopic staplers, whereas Group 2 (n = 158) consisted of patients who received the operation with GST and PVS.Results: Patient demographics and clinical characteristics were comparable, except smoking history, pulmonary function, and pleural adhesion. All patients received the operation successfully without mortalities and broncho-pleural fistula. Operation time and blood loss were higher in Group 1. Pleurodesis was performed less in Group 2 than in Group 1 (18.0% vs 3.8%, p < 0.0001). Group 2 had statistically significant lower adjusted hospital costs (Korean Won, 14,610,162 ± 4,386,628 vs 12,876,111 ± 5,010,878, p < 0.0001), lower adjusted hemostasis related costs (198,996 ± 110,253 vs 175,291 ± 191,003, p = 0.0101); lower cartridge related adjusted costs (1,105,091 ± 489,838 vs 839,011 ± 307,894, p < 0.0001) compared to Group 1. As well, Group 2 showed ∼12% lower adjusted total hospital costs compared to Group 1. Multivariable analysis revealed that Group 1 was related to increased hospital costs.Conclusions: This study showed that thoracoscopic lobectomy with powered and tissue-specific endoscopic staplers were associated with better clinical outcomes and reduced adjusted hospital costs when compared in Korean real-world settings.

mTORC1 accelerates retinal development via the immunoproteasome.

The numbers and types of cells constituting vertebrate neural tissues are determined by cellular mechanisms that couple neurogenesis to the proliferation of neural progenitor cells. Here we identified a role of mammalian target of rapamycin complex 1 (mTORC1) in the development of neural tissue, showing that it accelerates progenitor cell cycle progression and neurogenesis in mTORC1-hyperactive tuberous sclerosis complex 1 (Tsc1)-deficient mouse retina. We also show that concomitant loss of immunoproteasome subunit Psmb9, which is induced by Stat1 (signal transducer and activator of transcription factor 1), decelerates cell cycle progression of Tsc1-deficient mouse retinal progenitor cells and normalizes retinal developmental schedule. Collectively, our results establish a developmental role for mTORC1, showing that it promotes neural development through activation of protein turnover via a mechanism involving the immunoproteasome.

Association between supplementary private health insurance and visits to physician offices versus hospital outpatient departments among adults with diabetes in the universal public insurance system.

BACKGROUND: Diabetes mellitus is a chronic disease with a high prevalence across the world as well as in South Korea. Most cases of diabetes can be adequately managed at physician offices, but many diabetes patients receive outpatient care at hospitals. This study examines the relationship between supplementary private health insurance (SPHI) ownership and the use of hospitals among diabetes outpatients within the universal public health insurance scheme. METHODS: Data from the 2011 Korea Health Panel, a nationally representative sample of Korean individuals, was used. For the study, 6,379 visits for diabetes care were selected while controlling for clustered errors. Multiple logistic regression models were used to examine determinants of hospital outpatient services. RESULTS: This study demonstrated that the variables of self-rated health status, comorbidity, unmet need, and alcohol consumption significantly correlated with the choice to use a hospital services. Patients with SPHI were more likely to use medical services at hospitals by 1.71 times (95% CI 1.068-2.740, P = 0.026) compared to patients without SPHI. CONCLUSIONS: It was confirmed that diabetic patients insured by SPHI had more use of hospital services than those who were not insured. People insured by SPHI seem to be more likely to use hospital services because SPHI lightens the economic burden of care.

The Determinants of Choosing Traditional Korean Medicine or Conventional Medicine: Findings from the Korea Health Panel.

The purpose of this study is to identify key factors that determine a person's decision to seek treatment from traditional Korean medicine (TKM) instead of conventional medicine through analysis of nationally representative data from Korea, where a dual healthcare system exists. The analysis is based on episodic data from the 2008 and 2009 Korea Health Panel. The main dependent variable is the selection between TKM and conventional medicine. We used a multiple logistic regression model to identify the determinants of TKM while controlling for clustered error. Approximately 5% of all doctor's visits were characterized as TKM services. Urban residents were 1.441 times more likely to use TKM than rural residents (P = 0.001). The probability of choosing TKM over conventional medicine for a range of conditions compared to the reference condition (gastrointestinal disease) was as follows: circulatory system diseases (OR 5.267, P < 0.001), nervous system diseases (OR 12.054, P < 0.001), musculoskeletal system diseases (OR 20.579, P < 0.001), and neoplasms (OR 0.209, P = 0.004). Certain diseases are significantly more likely to be treated by TKM than by conventional medicine. This suggests that many people view TKM as being additionally effective for specific diseases, particularly musculoskeletal disorders.

Time trend of out-of-pocket expenditure among cancer inpatients: evidence from Korean tertiary hospitals.

BACKGROUND: This study aimed to examine out-of-pocket expenditure for cancer treatments of hospitalized patients and to analyze changing patterns over time. MATERIALS AND METHODS: This study examined data of all cancer patients receiving inpatient care from two tertiary hospitals from January 2003 to December 2010. Medical expenditures per admission were calculated and classified into those covered and uncovered by the Korean National Health Insurance (NHI) and co-payment. RESULTS: The medical expenditure per admission increased slowly from 3,455 thousand Korean won (KRW) to 4,068 thousand KRW. While expenditures covered by the NHI have increased annually, co-payments have generally decreased. The out-of-pocket expenditure ratio, which means the proportion of uncovered expenditure and co-payment among total medical expenditure dropped sharply from 2005 to 2007 and was maintained at a similar level after 2007. Medical expenditures, NHI coverage, and the out-of-pocket expenditure ratio differed across cancer types. CONCLUSIONS: It is necessary to continually monitor the expenditure of uncovered services by the NHI, and to provide policies to reduce this economic burden. In addition, an individual approach considering cancer type-specific characteristics and medical utilization should be provided.