3601 W 13 Mile Rd
Royal Oak MI 48073
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Mono-arginine Cholesterol-based Small Lipid Nanoparticles as a Systemic siRNA Delivery Platform for Effective Cancer Therapy. - Theranostics
Although efforts have been made to develop a platform carrier for the delivery of RNAi therapeutics, systemic delivery of siRNA has shown only limited success in cancer therapy. Cationic lipid-based nanoparticles have been widely used for this purpose, but their toxicity and undesired liver uptake after systemic injection owing to their cationic surfaces have hampered further clinical translation. This study describes the development of neutral, small lipid nanoparticles (SLNPs) made of a nontoxic cationic cholesterol derivative, as a suitable carrier of systemic siRNA to treat cancers. The cationic cholesterol derivative, mono arginine-cholesterol (MA-Chol), was synthesized by directly attaching an arginine moiety to cholesterol via a cleavable ester bond. siRNA-loaded SLNPs (siRNA@SLNPs) were prepared using MA-Chol and a neutral helper lipid, dioleoyl phosphatidylethanolamine (DOPE), as major components and a small amount of PEGylated phospholipid mixed with siRNA. The resulting nanoparticles were less than ~50 nm in diameter with neutral zeta potential and much lower toxicity than typical cationic cholesterol (DC-Chol)-based lipid nanoparticles. SLNPs loaded with siRNA against kinesin spindle protein (siKSP@SLNPs) exhibited a high level of target gene knockdown in various cancer cell lines, as shown by measurement of KSP mRNA and cell death assays. Furthermore, systemic injection of siKSP@SLNPs into prostate tumor-bearing mice resulted in preferential accumulation of the delivered siRNA at the tumor site and significant inhibition of tumor growth, with little apparent toxicity, as shown by body weight measurements. These results suggest that these SLNPs may provide a systemic delivery platform for RNAi-based cancer therapy.
Impact of postoperative complications on clinical and economic consequences in pancreatic surgery. - Annals of surgical treatment and research
Patients who develop complications consume a disproportionately large share of available resources in surgery; therefore the attention of healthcare funders focuses on the economic impact of complications. The main objective of this work was to assess the clinical and economic impact of postoperative complications in pancreatic surgery, and furthermore to assess risk factors for increased costs.In all, 161 consecutive patients underwent pancreatic resection. The costs of the treatment were determined and analyzed.The overall morbidity rate was 53.4%, and the in-hospital mortality rate was 3.7%. The median of costs for all patients without complication was 3,963 Euro, whereas the median of costs for patients with at least one complication was significantly increased at 10,670 Euro (P < 0.001). In multivariate analysis American Society of Anesthesiologists â‰¥ 3 (P = 0.006), multivisceral resection (P < 0.001) and any complication (P < 0.001) were independently associated with increased costs.Postoperative complications are associated with an increase in mortality, length of hospital stay, and hospital costs. The treatment costs increase with the severity of the postoperative complications. Those factors that are known to increase the treatment costs in pancreatic resection should be considered when planning patients for surgery.
Bioengineered yeast-derived vacuoles with enhanced tissue-penetrating ability for targeted cancer therapy. - Proceedings of the National Academy of Sciences of the United States of America
Despite the appreciable success of synthetic nanomaterials for targeted cancer therapy in preclinical studies, technical challenges involving their large-scale, cost-effective production and intrinsic toxicity associated with the materials, as well as their inability to penetrate tumor tissues deeply, limit their clinical translation. Here, we describe biologically derived nanocarriers developed from a bioengineered yeast strain that may overcome such impediments. The budding yeast Saccharomyces cerevisiae was genetically engineered to produce nanosized vacuoles displaying human epidermal growth factor receptor 2 (HER2)-specific affibody for active targeting. These nanosized vacuoles efficiently loaded the anticancer drug doxorubicin (Dox) and were effectively endocytosed by cultured cancer cells. Their cancer-targeting ability, along with their unique endomembrane compositions, significantly enhanced drug penetration in multicellular cultures and improved drug distribution in a tumor xenograft. Furthermore, Dox-loaded vacuoles successfully prevented tumor growth without eliciting any prolonged immune responses. The current study provides a platform technology for generating cancer-specific, tissue-penetrating, safe, and scalable biological nanoparticles for targeted cancer therapy.
The Protective Role of Resilience in Attenuating Emotional Distress and Aggression Associated with Early-life Stress in Young Enlisted Military Service Candidates. - Journal of Korean medical science
Early life stress (ELS) may induce long-lasting psychological complications in adulthood. The protective role of resilience against the development of psychopathology is also important. The purpose of this study was to investigate the relationships among ELS, resilience, depression, anxiety, and aggression in young adults. Four hundred sixty-one army inductees gave written informed consent and participated in this study. We assessed psychopathology using the Korea Military Personality Test, ELS using the Childhood Abuse Experience Scale, and resilience with the resilience scale. Analyses of variance, correlation analyses, and hierarchical multiple linear regression analyses were conducted for statistical analyses. The regression model explained 35.8%, 41.0%, and 23.3% of the total variance in the depression, anxiety, and aggression indices, respectively. We can find that even though ELS experience is positively associated with depression, anxiety, and aggression, resilience may have significant attenuating effect against the ELS effect on severity of these psychopathologies. Emotion regulation showed the most beneficial effect among resilience factors on reducing severity of psychopathologies. To improve mental health for young adults, ELS assessment and resilience enhancement program should be considered.
Intra-abdominal drainage following pancreatic resection: A systematic review. - World journal of gastroenterology
To study all the aspects of drain management in pancreatic surgery.We conducted a systematic review according to the PRISMA guidelines. We searched the Cochrane Central Registry of Controlled Trials, EMBASE, Web of Science, and PubMed (MEDLINE) for relevant articles on drain management in pancreatic surgery. The reference lists of relevant studies were screened to retrieve any further studies. We included all articles that reported clinical studies on human subjects with elective pancreatic resection and that compared various strategies of intra-abdominal drain management, such as drain vs no drain, selective drain use, early vs late drain extraction, and the use of different types of drains.A total of 19 studies concerned with drain management in pancreatic surgery involving 4194 patients were selected for this systematic review. We included studies analyzing the outcomes of pancreatic resection with and without intra-abdominal drains, studies comparing early vs late drain removal and studies analyzing different types of drains. The majority of the studies reporting equal or superior results for pancreatic resection without drains were retrospective and observational with significant selection bias. One recent randomized trial reported higher postoperative morbidity and mortality with routine omission of intra-abdominal drains. With respect to the timing of drain removal, all of the included studies reported superior results with early drain removal. Regarding the various types of drains, there is insufficient evidence to determine which type of drain is more suitable following pancreatic resection.The prophylactic use of drains remains controversial. When drains are used, early removal is recommended. Further trials comparing types of drains are ongoing.
Application of an Asthma Screening Questionnaire in Children with Sickle Cell Disease. - Pediatric allergy, immunology, and pulmonology
Objective: Asthma in sickle cell disease (SCD) patients is associated with elevated morbidity and mortality. Early detection and initiation of treatment may therefore lead to improved outcome. Utility of an asthma screening questionnaire to identify obstructive airway disease and physician diagnosed asthma in children with SCD at an outpatient setting as an effective, easy-to-administer screening tool has not previously been evaluated in this population. Methods: A previously validated asthma screening questionnaire and spirometry were prospectively administered to 41 SCD children at a routine clinic visit. Results: Prevalence of obstructive airway was 51.2% (nâ€‰=â€‰21) and physician diagnosis of asthma 33.3% (nâ€‰=â€‰13). Sensitivity (40%) and specificity (75%) of the questionnaire was poor in detecting obstructive airway disease, but sensitivity (77%), specificity (100%), positive predictive value (100%), and negative predictive value (90%) were high in detecting physician diagnosis of asthma. Conclusion: An asthma screening questionnaire could be a useful tool in identifying at-risk SCD children who may benefit from further management.
Use of a smartphone application to screen for bipolar spectrum disorder in a community sample. - Health informatics journal
This study describes the use of a smartphone application based on the Korean version of the Mood Disorder Questionnaire in screening for bipolar spectrum disorders in a large general population. All data were collected between May 2011 and July 2011. A total of 27,159 individuals participated in the survey, using a smartphone application. The prevalence of positive screening results for bipolar spectrum disorders among 27,159 participants using the smartphone Korean Mood Disorder Questionnaire application was 8.2â€‰percent. These results are similar to traditional paper-based results. The Korean Mood Disorder Questionnaire positive group exhibited more frequent occurrences of previous psychiatric treatment than the group with negative results. In a logistic regression analysis involving subjects with past psychiatric history, age group significantly predicted Korean Mood Disorder Questionnaire results. The smartphone application may be a useful screening tool for bipolar spectrum disorders. This study included only individuals who actively participated, and thus, the possibility of a selection bias should be considered.Â© The Author(s) 2015.
Korean Medication Algorithm for Bipolar Disorder 2014: comparisons with other treatment guidelines. - Neuropsychiatric disease and treatment
Our goal was to compare the recommendations of the Korean Medication Algorithm Project for Bipolar Disorder 2014 (KMAP-BP 2014) with other recently published guidelines for the treatment of bipolar disorder. We reviewed a total of four recently published global treatment guidelines and compared each treatment recommendation of the KMAP-BP 2014 with those in other guidelines. For the initial treatment of mania, there were no significant differences across treatment guidelines. All recommended mood stabilizer (MS) or atypical antipsychotic (AAP) monotherapy or the combination of an MS with an AAP as a first-line treatment strategy for mania. However, the KMAP-BP 2014 did not prefer monotherapy with MS or AAP for dysphoric/psychotic mania. Aripiprazole, olanzapine, quetiapine, and risperidone were the first-line AAPs in nearly all of the phases of bipolar disorder across the guidelines. Most guidelines advocated newer AAPs as first-line treatment options in all phases, and lamotrigine in depressive and maintenance phases. Lithium and valproic acid were commonly used as MSs in all phases of bipolar disorder. As research evidence accumulated over time, recommendations of newer AAPs - such as asenapine, paliperidone, lurasidone, and long-acting injectable risperidone - became prominent. This comparison identifies that the treatment recommendations of the KMAP-BP 2014 are similar to those of other treatment guidelines and reflect current changes in prescription patterns for bipolar disorder based on accumulated research data. Further studies are needed to address several issues identified in our review.
Targeted Therapy for Breast Cancer Stem Cells by Liposomal Delivery of siRNA against Fibronectin EDB. - Advanced healthcare materials
Targeted therapy for breast cancer stem cell (BCSC): A novel liposomal system (APTEDB -LS-siRNA(EDB) ) that enables simultaneous targeting and knockdown of extra domain B of fibronectin (EDB-FN) shows potent therapeutic efficacy in the BCSC-derived tumors in vivo.Â© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
DRAPA trial--closed-suction drains versus closed gravity drains in pancreatic surgery: study protocol for a randomized controlled trial. - Trials
The morbidity of pancreatic resection remains high, with pancreatic fistula being the most common cause. The important question is whether any postoperative treatment adjustment may prevent the development of clinically significant postoperative pancreatic fistulae. Recent studies have shown that intraabdominal drains and manipulation using them are of great importance. Although authors of a few retrospective reports have described good results of pancreatic resection without the use of intraabdominal drains, a recent prospective randomized trial showed that routine elimination of drains in pancreaticoduodenectomy is associated with poor outcome. An important issue arises as to which type of drain is most suitable for pancreatic resection. Two types of surgical drains exist: open drains and closed drains. Open drains are considered obsolete nowadays because of frequent retrograde infection. Closed drains include two types: passive gravity drains and closed-suction drains. Closed-suction drains are more effective, as they remove fluid from the abdominal cavity under light pressure. However, some surgeons believe that closed-suction drains represent a potential hazard to patients and that negative pressure might increase the risk of pancreatic fistulae. Nobody has yet specifically dealt with the question of which kind of drainage is most appropriate in pancreatic surgery.The aim of the DRAins in PAncreatic surgery (DRAPA) trial is to compare the closed-suction drain versus the closed passive gravity drain in pancreatic resection. DRAPA is a dual-centre, prospective, randomized controlled trial. The primary endpoint is the rate of postoperative pancreatic fistula; the secondary endpoint is postoperative morbidity with follow-up of 3 months.No study to date has compared different types of drains in pancreatic surgery. This study is designed to answer the question whether any particular type of drain might lower the rate of postoperative pancreatic fistula or other complications.ClinicalTrials.gov Identifier: NCT01988519. Registered 13 November 2013.
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3601 W 13 Mile Rd Royal Oak, MI 48073
3601 West 13 Mile Road
3601 W 13 Mile Rd