Usage Of Focused Assessment with Sonography in Trauma (Fast) Scan in Blunt Intraabdominal Trauma

Background Blunt intra-abdominal trauma (BAT) encompasses a major portion of trauma cases in the emergency department (ED). It poses a difficulty in diagnosis due to its low sensitivity and specificity of history and physical examination. Morison pouch is typically considered the most common area of free fluid (FF) in BAT visualized on the focused assessment with sonography in trauma (FAST) scan. However, no studies to date have investigated the correlation of the abdominal quadrant for positive FF with the type of abdominal trauma. This study aims to determine the most common quadrant and subquadrants for detecting FF and their association with the type of injury in BAT patients. Methods This multicenter study evaluated 86 BAT patients who presented to the ED. The FAST scan was performed per trauma life support protocol, and video clips were extracted for patients with positive FAST findings confirmed by abdominal computed tomography (CT) or exploratory laparotomy. The most common quadrant and subquadrant positive for FF were then determined. Positive quadrants and their association with type of injury were also analyzed. Areas studied were the right upper quadrant (RUQ), left upper quadrant (LUQ), and suprapubic area (SP). Subquadrant areas were RUQ 1–hepato-diaphragmatic; RUQ 2–Morison pouch; RUQ 3–caudal liver edge and superior para-colic gutter; LUQ 1–splenicdiaphragmatic; LUQ 2–spleno-renal; LUQ 3–around the inferior pole of kidney; SP 1–bilateral to bladder; SP 2–posterior to bladder; and SP 3–posterior to uterus. Results The most frequent region with positive FF results was the RUQ, seen in 82 (95.3%) patients. In subquadrant analysis, RUQ 3 was the most common region (78 patients, 90.75%), followed by RUQ 2 (73 patients, 84.9%) and LUQ 2 (51 patients, 59.3%). A significant association was observed between the LUQ region positive for FF and the presence of splenic injury (p = 0.006). Conclusion In patients with BAI, the RUQ is the most frequent quadrant and RUQ 3 is the most frequent subquadrant positive FF. A positive LUQ free fluid suggests the presence of splenic injury in BAT

Beneficial Effects of a Curcumin Derivative and Transforming Growth Factor-β Receptor I Inhibitor Combination on Nonalcoholic Steatohepatitis

Background Curcumin 2005-8 (Cur5-8), a derivative of curcumin, improves fatty liver disease via AMP-activated protein kinase activation and autophagy regulation. EW-7197 (vactosertib) is a small molecule inhibitor of transforming growth factor β (TGF-β) receptor I and may scavenge reactive oxygen species and ameliorate fibrosis through the SMAD2/3 canonical pathway. This study aimed to determine whether co-administering these two drugs having different mechanisms is beneficial. Methods Hepatocellular fibrosis was induced in mouse hepatocytes (alpha mouse liver 12 [AML12]) and human hepatic stellate cells (LX-2) using TGF-β (2 ng/mL). The cells were then treated with Cur5-8 (1 μM), EW-7197 (0.5 μM), or both. In animal experiments were also conducted during which, methionine-choline deficient diet, Cur5-8 (100 mg/kg), and EW-7197 (20 mg/kg) were administered orally to 8-week-old C57BL/6J mice for 6 weeks. Results TGF-β-induced cell morphological changes were improved by EW-7197, and lipid accumulation was restored on the administration of EW-7197 in combination with Cur5-8. In a nonalcoholic steatohepatitis (NASH)-induced mouse model, 6 weeks of EW-7197 and Cur5-8 co-administration alleviated liver fibrosis and improved the nonalcoholic fatty liver disease (NAFLD) activity score. Conclusion Co-administering Cur5-8 and EW-7197 to NASH-induced mice and fibrotic hepatocytes reduced liver fibrosis and steatohepatitis while maintaining the advantages of both drugs. This is the first study to show the effect of the drug combination against NASH and NAFLD. Similar effects in other animal models will confirm its potential as a new therapeutic agent

Triptolide-Mediated Apoptosis by Suppression of Focal Adhesion Kinase through Extrinsic and Intrinsic Pathways in Human Melanoma Cells

Triptolide (TPL) has been shown to inhibit cell proliferation and induce apoptosis in various human cancer cells; however, the precise mechanism of apoptosis induced by TPL in human melanoma cells has not yet been elucidated. In this study, we investigated the precise mechanism underlying cytocidal effects of TPL on human melanoma cells. Treatment of human melanoma cells with TPL significantly inhibited cell growth and induced apoptosis, as evidenced by flow cytometry and annexin V-fluorescein isothiocyanate analyses. TPL increased the levels of Fas and Fas-associated death domain (FADD) and induced cleavage of Bid by activation of caspase-8 and cytochrome c release from mitochondria to the cytosol, which resulted in activation of caspase-9 and caspase-3. Moreover, TPL-induced apoptosis in SK-MEL-2 cells was mediated through dephosphorylation of focal adhesion kinase (FAK) and its cleavage by caspase-8-mediated caspase-3 activation via upregulation of Fas expression. We also found that TPL mediated the dissociation of receptor-interacting protein (RIP) from FAK and enhanced the formation of RIP/Fas complex formation initiating cell death. In conclusion, our data firstly demonstrated that TPL induces apoptosis by both extrinsic and intrinsic apoptosis pathways in human melanoma cells and identified that RIP shuttles between Fas and FAK to mediate apoptosis

Amifostine ameliorates recognition memory defect in acute radiation syndrome caused by relatively low-dose of gamma radiation

This study examined whether amifostine (WR-2721) could attenuate memory impairment and suppress hippocampal neurogenesis in adult mice with the relatively low-dose exposure of acute radiation syndrome (ARS). These were assessed using object recognition memory test, the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, and immunohistochemical markers of neurogenesis [Ki-67 and doublecortin (DCX)]. Amifostine treatment (214 mg/kg, i.p.) prior to irradiation significantly attenuated the recognition memory defect in ARS, and markedly blocked the apoptotic death and decrease of Ki-67- and DCX-positive cells in ARS. Therefore, amifostine may attenuate recognition memory defect in a relatively low-dose exposure of ARS in adult mice, possibly by inhibiting a detrimental effect of irradiation on hippocampal neurogenesis

Ninjurin1 drives lung tumor formation and progression by potentiating Wnt/β-Catenin signaling through Frizzled2-LRP6 assembly

Cancer stem-like cells (CSCs) play a pivotal role in lung tumor formation and progression. Nerve injury-induced protein 1 (Ninjurin1, Ninj1) has been implicated in lung cancer; however, the pathological role of Ninj1 in the context of lung tumorigenesis remains largely unknown. The role of Ninj1 in the survival of non-small cell lung cancer (NSCLC) CSCs within microenvironments exhibiting hazardous conditions was assessed by utilizing patient tissues and transgenic mouse models where Ninj1 repression and oncogenic KrasG12D/+ or carcinogen-induced genetic changes were induced in putative pulmonary stem cells (SCs). Additionally, NSCLC cell lines and primary cultures of patient-derived tumors, particularly Ninj1high and Ninj1low subpopulations and those with gain- or loss-of-Ninj1 expression, and also publicly available data were all used to assess the role of Ninj1 in lung tumorigenesis. Ninj1 expression is elevated in various human NSCLC cell lines and tumors, and elevated expression of this protein can serve as a biomarker for poor prognosis in patients with NSCLC. Elevated Ninj1 expression in pulmonary SCs with oncogenic changes promotes lung tumor growth in mice. Ninj1high subpopulations within NSCLC cell lines, patient-derived tumors, and NSCLC cells with gain-of-Ninj1 expression exhibited CSC-associated phenotypes and significantly enhanced survival capacities in vitro and in vivo in the presence of various cell death inducers. Mechanistically, Ninj1 forms an assembly with lipoprotein receptor-related protein 6(LRP6) through its extracellular N-terminal domain and recruits Frizzled2 (FZD2) and various downstream signaling mediators, ultimately resulting in transcriptional upregulation of target genes of the LRP6/β-catenin signaling pathway. Ninj1 may act as a driver of lung tumor formation and progression by protecting NSCLC CSCs from hostile microenvironments through ligand-independent activation of LRP6/β-catenin signaling.This study was supported by the grants from the National Research Founda‑tion of Korea (NRF), the Ministry of Science and ICT (MSIT), Republic of Korea (No. NRF-2016R1A3B1908631)

Journey with Ting-Peng Liang in Pacific Asia Information Systems Field

Our respectful old friend Professor Ting-Peng Liang (in short, TP) whom we loved suddenly passed away on May 20, 2021. But we cannot forget his smile and passion, and his inerasable footprints in PACIS, PAJAIS, and AIS Community. He was the founder of PACIS, founding editor-in-chief of PAJAIS, and past president of AIS to list just a few. He was the pioneer who received the first AIS Fellow and the first LEO Award from Asia Pacific. That is why the leaders of the information systems field organized the first ever special tribute session in PACIS 2021 in memory of TP (https://aisel.aisnet.org/pacis2021/253/

Development of a novel direct compressible co-processed excipient and its application for formulation of Mirtazapine orally disintegrating tablets

Introduction: Orally disintegrating tablets (ODTs) are designed to dissolve in the oral cavity within 3 min, providing a convenient option for patients as they can be taken without water. Direct compression is the most common method used for ODTs formulations. However, the availability of single composite excipients with desirable characteristics such as good compressibility, fast disintegration, and a good mouth-feel suitable for direct compression is limited. Objective: This research was proposed to develop a co-processed excipient composed of xylitol, mannitol, and microcrystalline cellulose for the formulation of ODTs. Methods: A total of 11 formulations of co-processed excipients with different ratios of ingredients were prepared, which were then compressed into ODTs, and their characteristics were thoroughly examined. The primary focus was on evaluating the disintegration time and hardness of the tablets, as these factors are important in ensuring the ODTs meet the desired criteria. The model drug, Mirtazapine was then incorporated into the chosen optimized formulation. Results: The results showed that the formulation comprised of 10% xylitol, 10% mannitol and 80% micro-crystalline cellulose demonstrated the fastest disintegration time (1.77 ± 0.119 min) and sufficient hardness (3.521 ± 0.143 kg) compared to the other formulations. Furthermore, the drug was uniformly distributed within the tablets and fully released within 15 min. Conclusion: Therefore, the developed co-processed excipients show great potential in enhancing the functionalities of ODTs, offering a promising solution to improve the overall performance and usability of ODTs in various therapeutic applications

Exaggeration of wrinkles after botulinum toxin injection for forehead horizontal lines

There have been no long-term complications or life-threatening adverse effects related to botulinum toxin treatment for any cosmetic indications. Nevertheless, there are well-known, mild side effects of botulinum toxin treatment on the upper face, though most of them are self limited with time. However, excluding brow ptosis, reports about site specific side effects are few and anecdotal. We experienced cases of exaggeration of wrinkles after botulinum toxin injection for forehead horizontal lines, and report them here. In our cases, new appearance of a noticeable glabellar protrusion following botulinum toxin injection on the forehead was observed in 2 patients. Also, a new deep wrinkle on one side of the forehead just above the eyebrow appeared in another 2 patients. The exaggerated wrinkles nearly disappeared without treatment by week 4 in all subjects. These exaggerations of wrinkles may be caused by hyperactivity and overcompensation of untreated muscles. With the increasing availability of diverse botulinum toxin for cosmetic purposes, physicians and patients should be aware of this temporary change after therapeutic injections. We recommend explaining this possible effect prior to injection, for better understanding of treatment for cosmetic indications.OAIID:oai:osos.snu.ac.kr:snu2011-01/102/2008000790/3SEQ:3PERF_CD:SNU2011-01EVAL_ITEM_CD:102USER_ID:2008000790ADJUST_YN:NEMP_ID:A079501DEPT_CD:801CITE_RATE:.531FILENAME:botox and wrinkles.pdfDEPT_NM:의학과SCOPUS_YN:NCONFIRM:

Therapeutic potential of cladribine in combination with STAT3 inhibitor against multiple myeloma

<p>Abstract</p> <p>Background</p> <p>Cladribine or 2-chlorodeoxyadenosine (2-CDA) is a well-known purine nucleoside analog with particular activity against lymphoproliferative disorders, such as hairy cell leukemia (HCL). Its benefits in multiple myeloma (MM) remain unclear. Here we report the inhibitory effects of cladribine on MM cell lines (U266, RPMI8226, MM1.S), and its therapeutic potential in combination with a specific inhibitor of the signal transducer and activator of transcription 3 (STAT3).</p> <p>Methods</p> <p>MTS-based proliferation assays were used to determine cell viability in response to cladribine. Cell cycle progression was examined by flow cytometry analysis. Cells undergoing apoptosis were evaluated with Annexin V staining and a specific ELISA to quantitatively measure cytoplasmic histone-associated DNA fragments. Western blot analyses were performed to determine the protein expression levels and activation.</p> <p>Results</p> <p>Cladribine inhibited cell proliferation of MM cells in a dose-dependent manner, although the three MM cell lines exhibited a remarkably different responsiveness to cladribine. The IC50 of cladribine for U266, RPMI8226, or MM1.S cells was approximately 2.43, 0.75, or 0.18 μmol/L, respectively. Treatment with cladribine resulted in a significant G1 arrest in U266 and RPMI8226 cells, but only a minor increase in the G1 phase for MM1.S cells. Apoptosis assays with Annexin V-FITC/PI double staining indicated that cladribine induced apoptosis of U266 cells in a dose-dependent manner. Similar results were obtained with an apoptotic-ELISA showing that cladribine dramatically promoted MM1.S and RPMA8226 cells undergoing apoptosis. On the molecular level, cladribine induced PARP cleavage and activation of caspase-8 and caspase-3. Meanwhile, treatment with cladribine led to a remarkable reduction of the phosphorylated STAT3 (P-STAT3), but had little effect on STAT3 protein levels. The combinations of cladribine and a specific STAT3 inhibitor as compared to either agent alone significantly induced apoptosis in all three MM cell lines.</p> <p>Conclusions</p> <p>Cladribine exhibited inhibitory effects on MM cells <it>in vitro</it>. MM1.S is the only cell line showing significant response to the clinically achievable concentrations of cladribine-induced apoptosis and inactivation of STAT3. Our data suggest that MM patients with the features of MM1.S cells may particularly benefit from cladribine monotherapy, whereas cladribine in combination with STAT3 inhibitor exerts a broader therapeutic potential against MM.</p