Improving STING Agonist Delivery for Cancer Immunotherapy Using Biodegradable Mesoporous Silica Nanoparticles

Stimulator of interferon genes (STING) activation by intratumoral STING agonist treatment has been recently shown to eradicate tumors in preclinical models of cancer immunotherapy, generating intense research interest and leading to multiple clinical trials. However, there are many challenges associated with STING agonist‐based cancer immunotherapy, including low cellular uptake of STING agonists. Here, biodegradable mesoporous silica nanoparticles (bMSN) with an average size of 80 nm are developed for efficient cellular delivery of STING agonists. STING agonists delivered via bMSN potently activate innate and adaptive immune cells, leading to strong antitumor efficacy and prolonged animal survival in murine models of melanoma. Delivery of immunotherapeutic agents via biodegradable bMSN is a promising approach for improving cancer immunotherapy.Biodegradable mesoporous silica nanoparticles enhance cellular delivery of stimulator of interferon genes (STING) agonists and achieve greater antitumor therapeutic efficacy than free STING agonists in murine models of melanoma. Biodegradable mesoporous silica nanoparticles are a promising platform for cancer immunotherapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163388/3/adtp202000130_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163388/2/adtp202000130.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163388/1/adtp202000130-sup-0001-SuppMat.pd

Controlling shareholders’ ownership structure, foreign investors’ monitoring, and investment efficiency

This study examines the effect of control-ownership wedge (the difference between control rights and cash flow rights) on investment efficiency. Subsequently, the authors analyze how the level of foreign investor monitoring influences the association between control-ownership wedge and investment efficiency. The results of the analyses show that investment efficiency deteriorates as control-ownership wedge increases. This, in turn, suggests that when this wedge increases, agency problems and information asymmetry between controlling and minority shareholders become more severe. The authors also perform an analysis by dividing the samples into four groups based on foreign investor ratio from the least to the greatest. The result shows that control-ownership wedge deteriorates investment efficiency in the group with the least foreign investor ratio. The result reveals that foreign investor monitoring is effective corporate governance mechanism to monitor the controlling shareholders’ investment decisions. We also find that higher control-ownership wedge with over-investment tendency negatively affects firm performance, which implies an inefficient investment behavior. This result suggests that as controlling shareholders’ ownership increases, controlling shareholders becomes more and more reluctant to assume a loss of firm value as a result of reduced investment efficiency. This study provides additional evidence that the greater control-ownership wedge decreases investment efficiency, while recent studies on the relation between control-ownership wedge and investment efficiency suggest mixed evidence. In addition, the results show that foreign investors play an effective monitoring role when controlling shareholders are in position of exercising exclusive power. The results indicate the importance of external investors’ monitoring over investment decisions. Keywords: control-ownership wedge, foreign ownership, investment efficiency, over-investment, under-investment. JEL Classification: G32, M4

Ductographic Findings of Breast Cancer

Ductography has become the gold standard for the evaluation of patients exhibiting pathologic nipple discharges. In nine patients (age range, 29-67 years; median age, 51 years) with invasive (n=5) or intraductal (n=4) cancer, ductographic findings were recorded, then correlated with mammographic and sonographic findings. Common ductographic findings included complete ductal obstruction, multiple irregular filling defects in the nondilated peripheral ducts, ductal wall irregularities, periductal contrast extravasation, and ductal displacement. Faint microcalcifications or ill-defined masses, which were not opacified by contrast material, were often discovered adjacent to ductal abnormalities. Mammographically and sonographically occult diffusely spreading intraductal cancers often manifested as pathologic nipple discharge. In such cases, meticulous ductographic examinations and interpretations were crucial in order not to miss breast cancers

Asymptomatic subjects with diabetes have a comparable risk of coronary artery disease to Non-diabetic subjects presenting chest pain: a 4-year community-based prospective study

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background Although diabetes mellitus is an important risk factor of coronary artery disease (CAD), routine screening for CAD is not recommended for asymptomatic diabetic patients. We assessed the impact of chest pain on CAD risk according to the presence or absence of diabetes mellitus. Methods We investigated the future CAD event rate in subjects with and without chest pain according to the presence or absence of diabetes in a prospective large-scale community-based study in Korea. Results Among 8,574 subjects (4,032 men and 4,542 women) without a history of CAD, 0.8% and 2.2% of non-diabetic and diabetic subjects, respectively, reported newly developed CAD events during 4 years of follow-up. Although the presence of chest pain at baseline was also significantly associated with an increased risk of CAD of more than 2-fold in both non-diabetic and diabetic subjects (P < 0.01), the risk of future CVD event in asymptomatic diabetic patients was not significantly different from that in non-diabetic subjects with chest pain (hazard ratio, 0.907; 95% confidence interval, 0.412 – 1.998). Conclusions The CAD event rate of asymptomatic subjects with diabetes was comparable to that of non-diabetic subjects reporting chest pain. Considering the high risk of CAD in asymptomatic diabetic patients, more clinical trials aimed at formulating strategies to screen asymptomatic diabetic subjects should be carried out

Renal transplantation in a patient with Bartter syndrome and glomerulosclerosis

Bartter syndrome (BS) is a clinically and genetically heterogeneous inherited renal tube disorder characterized by renal salt wasting, hypokalemic metabolic alkalosis and normotensive hyperreninemic hyperaldosteronism. There have been several case reports of BS complicated by focal segmental glomerulosclerosis (FSGS). Here, we have reported the case of a BS patient who developed FSGS and subsequent end-stage renal disease (ESRD) and provided a brief literature review. The patient presented with classic BS at 3 months of age and developed proteinuria at 7 years. Renal biopsy performed at 11 years of age revealed a FSGS perihilar variant. Hemodialysis was initiated at 11 years of age, and kidney transplantation was performed at 16 years of age. The post-transplantation course has been uneventful for more than 3 years with complete disappearance of BS without the recurrence of FSGS. Genetic study revealed a homozygous p.Trp(TGG)610Stop(TGA) mutation in the CLCNKB gene. In summary, BS may be complicated by secondary FSGS due to the adaptive response to chronic salt-losing nephropathy, and FSGS may progress to ESRD in some patients. Renal transplantation in patients with BS and ESRD results in complete remission of BS

Recurred pneumocephalus in a head trauma patient following positive pressure mask ventilation during induction of anesthesia -A case report-

Pneumocephalus is a condition which usually results from head trauma. It has been known that iatrogenic pneumocephalus can occur as a complication of positive pressure mask ventilation during induction of anesthesia or ventilatory care for head trauma patients. We report a case of mask ventilation during anesthesia induction in a 50-year-old male patient with head trauma. Initial pneumocephalus associated with cerebrospinal fluid leakage was diagnosed immediate following head injury involving facial sinuses. He was managed with emergent lumbar drainage and supportive care. Pneumocephalus recurred following positive pressure mask ventilation (PPMV) during anesthesia induction for surgery on the right arm. Recurred pneumocephalus was managed with high flow oxygen and supportive care. Anesthesiologists should be aware of pneumocephalus as a potential complication of PPMV in head trauma patients, even after resolution of previous pneumocephalus

Identification of the early and late responder genes during the generation of induced pluripotent stem cells from mouse fibroblasts

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