Dendrimer-Encapsulated Nanoparticles: New Synthetic and Characterization Methods and Catalytic Applications

In this article we describe the synthesis, characterization, and applications of dendrimer-encapsulated nanoparticles (DENs). These materials are synthesized using a template approach in which metal ions are extracted into the interior of dendrimers and then subsequently reduced chemically to yield nearly size-monodisperse particles having diameters in the 1-2 nm range. Monometallic, bimetallic (alloy and core@shell), and semiconductor nanoparticles have been prepared by this route. The dendrimer component of these composites serves not only as a template for preparing the nanoparticle replica, but also as a stabilizer for the nanoparticle. In this perspective, we report on progress in the synthesis, characterization, and applications of these materials since our last review in 2005. Significant advances in the synthesis of core@shell DENs, characterization, and applications to homogeneous and heterogeneous catalysis (including electrocatalysis) are emphasized.U.S. Department of Energy, Office of Basic Energy Sciences DE-FG02-09ER16090U.S. National Science Foundation 0847957Robert A. Welch Foundation F-0032Chemistr

The Prognostic Significance of the Preoperative Full Blood Count after Resection of Colorectal Liver Metastases

Introduction. Increased preoperative platelet and neutrophil counts are risk factors for decreased survival in several different malignancies. Our aim was to investigate the relationship between overall or disease-free survival after resection of CRLM and the preoperative haematological parameters. Methods. We reviewed a cohort of 140 patients who underwent resection of CRLM with curative intent, utilising prospectively maintained databases. Patient demographics, operative details, FBC, CRP, INR, histopathology results, and survival data were examined. Kaplan-Meier survival and Cox regression analyses were used to determine the impact of all variables on survival. Results. 140 patients (96 males) with a median age of 67 years (range 33–82 years) underwent resection of CRLM. A significant correlation was exhibited between preoperative platelet count and neutrophil count (rho = 0.186, P = .028). When modelled as continuous covariates in a Cox regression hazards, an increased preoperative platelet (P = .02) and neutrophil counts (P ≤ .001) were significantly associated with overall survival. Of the haematological parameters assessed only preoperative platelet count showed a strong trend of association with disease free survival; however this failed to reach statistical significance (P = .076). Conclusions. Increased preoperative platelet and neutrophil counts are independent risk factors for decreased survival in patients undergoing resection of CRLM in our series of patients. These findings require validation in larger studies to determine their relationship with survival. Further research into the role of these cell types in tumour progression, particularly in the development and inhibition of angiogenesis, is warranted

Parallel Evaluation of Multi-join Queries

A number of execution strategies for parallel evaluation of multi-join queries have been proposed in the literature. In this paper we give a comparative performance evaluation of four execution strategies by implementing all of them on the same parallel database system, PRISMA/DB. Experiments have been done up to 80 processors. These strategies, coming from the literature, are named: Sequential Parallel, Synchronous Execution, Segmented Right-Deep, and Full Parallel. Based on the experiments clear guidelines are given when to use which strategy. This is an extended abstract; the full paper appeared in Proc. ACM SIGMOD'94, Minneapolis, Minnesota, May 24–27, 199

Timed up and go test and long-term survival in older adults after oncologic surgery

BACKGROUND: Physical performance tests are a reflection of health in older adults. The Timed Up and Go test is an easy-to-administer tool measuring physical performance. In older adults undergoing oncologic surgery, an impaired TUG has been associated with higher rates of postoperative complications and increased short term mortality. The objective of this study is to investigate the association between physical performance and long term outcomes. METHODS: Patients aged ≥65 years undergoing surgery for solid tumors in three prospective cohort studies, ‘PICNIC’, ‘PICNIC B-HAPPY’ and ‘PREOP’, were included. The TUG was administered 2 weeks before surgery, a score of ≥12 seconds was considered to be impaired. Primary endpoint was 5-year survival, secondary endpoint was 30-day major complications. Survival proportions were estimated using Kaplan-Meier curves. Cox- and logistic regression analysis were used for survival and complications respectively. Hazard ratios (aHRs) and Odds ratios (aOR) were adjusted for literature-based and clinically relevant variables, and 95% confidence intervals (95% CIs) were estimated using multivariable models. RESULTS: In total, 528 patients were included into analysis. Mean age was 75 years (SD 5.98), in 123 (23.3%) patients, the TUG was impaired. Five-year survival proportions were 0.56 and 0.49 for patients with normal TUG and impaired TUG respectively. An impaired TUG was an independent predictor of increased 5-year mortality (aHR 1.43, 95% CI 1.02-2.02). The TUG was not a significant predictor of 30-day major complications (aOR 1.46, 95% CI 0.70-3.06). CONCLUSIONS: An impaired TUG is associated with increased 5-year mortality in older adults undergoing surgery for solid tumors. It requires further investigation whether an impaired TUG can be reversed and thus improve long-term outcomes. TRIAL REGISTRATION: The PICNIC studies are registered in the Dutch Clinical Trial database at www.trialregister.nl: NL4219 (2010-07-22) and NL4441 (2014-06-01). The PREOP study was registered with the Dutch trial registry at www.trialregister.nl: NL1497 (2008-11-28) and in the United Kingdom register (Research Ethics Committee reference 10/H1008/59). https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/?page=15&query=preop&date_from=&date_to=&research_type=&rec_opinion=&relevance=true. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12877-022-03585-4

Long-Term Survival and Risk of Institutionalization in Onco-Geriatric Surgical Patients:Long-Term Results of the PREOP Study

OBJECTIVES: To evaluate long-term survival and institutionalization in onco-geriatric surgical patients, and to analyze the association between these outcomes and a preoperative risk score. DESIGN: Prospective cohort study with long-term follow-up. SETTING: International and multicenter locations. PARTICIPANTS: Patients aged 70 years or older undergoing elective surgery for a malignant solid tumor at five centers (n = 229). MEASUREMENTS: We assessed long-term survival and institutionalization using the Preoperative Risk Estimation for Onco-geriatric Patients (PREOP) score, developed to predict the 30-day risk of major complications. The PREOP score collected data about sex, type of surgery, and the American Society for Anesthesiologists classification, as well as the Timed Up & Go test and the Nutritional Risk Screening results. An overall score higher than 8 was considered abnormal. RESULTS: We included 149 women and 80 men (median age = 76 y; interquartile range = 8). Survival at 1, 2, and 5 years postoperatively was 84%, 77%, and 56%, respectively. Moreover, survival at 1 year was worse for patients with a PREOP risk score higher than 8 (70%) compared with 8 or lower (91%). Of those alive at 1 year, 43 (26%) were institutionalized, and by 2 years, almost half of the entire cohort (46%) were institutionalized or had died. A PREOP risk score higher than 8 was associated with increased mortality (hazard ratio = 2.6; 95% confidence interval [CI] = 1.7-4.0), irrespective of stage and age, but not with being institutionalized (odds ratios = 1 y, 1.6 [95% CI =.7-3.8]; 2 y, 2.2 [95% CI =.9-5.5]). CONCLUSION: A high PREOP score is associated with mortality but not with remaining independent. Despite acceptable survival rates, physical function may deteriorate after surgery. It is imperative to discuss treatment goals and expectations preoperatively to determine if they are feasible. Using the PREOP risk score can provide an objective measure on which to base decisions. J Am Geriatr Soc 68:1235–1241, 2020

Discovery of a AHR pelargonidin agonist that counter-regulates Ace2 expression and attenuates ACE2-SARS-CoV-2 interaction

The severe acute respiratory syndrome (SARS)-CoV-2 is the pathogenetic agent of Corona Virus Induced Disease (COVID)19. The virus enters the human cells after binding to the angiotensin converting enzyme (ACE)2 receptor in target tissues. ACE2 expression is induced in response to inflammation. The colon expression of ACE2 is upregulated in patients with inflammatory bowel disease (IBD), highlighting a potential risk of intestinal inflammation in promoting viral entry in the human body. Because mechanisms that regulate ACE2 expression in the intestine are poorly understood and there is a need of anti-SARS-CoV-2 therapies, we have settled to investigate whether natural flavonoids might regulate the expression of Ace2 in intestinal models of inflammation. The results of these studies demonstrated that pelargonidin activates the Aryl hydrocarbon Receptor (AHR) in vitro and reverses intestinal inflammation caused by chronic exposure to high fat diet or to the intestinal braking-barrier agent TNBS in a AhR-dependent manner. In these two models, development of colon inflammation associated with upregulation of Ace2 mRNA expression. Colon levels of Ace2 mRNA were directly correlated with Tnf-α mRNA levels. Molecular docking studies suggested that pelargonidin binds a fatty acid binding pocket on the receptor binding domain of SARS-CoV-2 Spike protein. In vitro studies demonstrated that pelargonidin significantly reduces the binding of SARS-CoV-2 Spike protein to ACE2 and reduces the SARS-CoV-2 replication in a concentration-dependent manner. In summary, we have provided evidence that a natural flavonoid might hold potential in reducing intestinal inflammation and ACE2 induction in the inflamed colon in a AhR-dependent manner

"A few good men": Public sector audit in the Swan River Colony, 1828-1835

The appointment of the Auditor General to undertake public sector audit is the primary instrument used to safeguard public finances in most contemporary Westminster-based democracies. It is axiomatic that the independence of the Auditor General from executive government is a critical element in ensuring the effectiveness of the role, yet this separation is a relatively recent phenomenon. Those responsible for nineteenth century public sector audit in the Australian colonies operated in what would today be considered an unacceptable environment, with little, if any, independence from the executive arm of government. Yet, while several other Australian colonies suffered from the mismanagement of government finances, there is nothing to show that the Swan River Colony experienced much more than clerical errors and minor administrative oversights. In this article, we explore the extent to which satisfactory public financial management in the Swan River Colony occurred as a result of both good financial management systems (in the context of the era) and the appointment of competent and ethical administrators – “a few good men”

Extensive necrosis of visceral melanoma metastases after immunotherapy

<p>Abstract</p> <p>Background</p> <p>The prognosis for metastatic melanoma remains poor even with traditional decarbazine or interferon therapy. 5-year survival is markedly higher amongst patients undergoing metastatectomy. Unfortunately not all are suitable for metastatectomy. Alternative agents for systemic therapy have, to date, offered no greater rates of survival beyond traditional therapy. A toll-like receptor 9 agonist, PF-3512676 (formerly known as CPG 7909) is currently being evaluated for its potential.</p> <p>Case presentation</p> <p>We present the case of a 54-year-old Caucasian male with completely resected metastatic cutaneous melanoma after immunotherapy. The patient initially progressed during adjuvant high-dose interferon, with metastases to the liver, spleen, and pelvic lymph nodes. During an 18-month treatment period with PF-3512676 (formerly known as CPG 7909), a synthetic cytosine-phosphorothioate-guanine rich oligodeoxynucleotide, slow radiologic disease progression was demonstrated at the original disease sites. Subsequent excision of splenic and pelvic nodal metastases was performed, followed by resection of the liver metastases. Histologic examination of both hepatic and splenic melanoma metastases showed extensive necrosis. Subsequent disease-free status was demonstrated by serial positron emission tomography (PET).</p> <p>Conclusion</p> <p>Existing evidence from phase I/II trials suggests systemic treatment with PF-3512676 is capable of provoking a strong tumor-specific immune response and may account for the prolonged tumor control in this instance.</p

Correction: "Timed Up &amp; Go":A Screening Tool for Predicting 30-Day Morbidity in Onco-Geriatric Surgical Patients? A Multicenter Cohort Study (vol 9, e0086863, 2014)

<p>Correction: "Timed Up & Go": A Screening Tool for Predicting 30-Day Morbidity in Onco-Geriatric Surgical Patients? <i>A Multicenter Cohort Study</i></p