Intensive cyclic chemotherapy and transplantation of autologous peripheral blood progenitor cells (PBPC) or whole blood in high-risk breast cancer — follow up at 10 years

Aim: The main aim of our paper is to contribute to objectification of currently widely discussed results of overall survival (OS), disease free survival (DFS) and time from relapse to tumor progression (TTP) in women with breast cancer. Methods: Forty consecutive patients fulfilling the eligibility criteria were admitted to the study. Fifty-six women were included in the control group. All patients received 6 cycles of adjuvant intensive cyclic combined chemotherapy with epirubicin 150 mg/m2 and cyclophosphamide 1250 mg/m2 (EC) applied each 14 days. To overcome haematological toxicity transplantations of autologous peripheral blood progenitor cells (PBPCs) or whole blood enriched of PBPC were used. Results: We found statistically significant difference in OS regardless of the stage of the disease to the benefit of women treated by intensive cyclic EC chemotherapy when compared with the control group. In evaluation of DFS no statistically significant difference was found in survival between the control group and the group with all stages of the disease. TTP in women without relation to the stage was statistically significantly longer than in the control group. Conclusion: In our study intensive cyclic EC chemotherapy did not show better curative effect when compared with conventional dosage chemotherapy.Цель:объективизация широко обсуждаемых результатов по общей выживаемости (OВ), периода ремиссии (ПР) и продолжительности периода от рецидива к опухолевой прогрессии (ПРОП) у больных раком молочной железы. Методы: обследовано 40 больных, отвечающих установленным критериям отбора, и 56 здоровых женщин, составивших контрольную группу. У всех больных проведено 6 циклов адъювантной интенсивной циклической комбинированной химио­терапии (эпирубицин — 150 мг/м2 и циклофосфамид — 1250 мг/м2 (ЭЦ)), проводимой каждые 14 дней. Для преодоления гематологической токсичности применяли трансплантацию клеток-предшественников периферической крови (КППК) или цельной крови, обогащенной КППК. Результаты: выявлены статистически значимые различия в ОВ, не зависящие от стадии заболевания, у пациенток, получавших интенсивную циклическую химиотерапию ЭЦ, по сравнению с контрольной группой. При оценке ПР не выявлено статистически значимых различий выживаемости между контрольной группой и больными во всех стадиях заболевания. ПРОП у пациенток независимо от стадии заболевания статистически значимо выше, чем таковой контрольной группы. Выводы: по результатам исследования, интенсивная циклическая химиотерапия ЭЦ не имеет лечебных преимуществ по сравнению со стандартной дозовой химиотерапией

Use of Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry to Demonstrate Decreased Serum Statin Levels after Extracorporeal LDL-Cholesterol Elimination

Background. Using our statin analysis method, it was possible to uncover a significant drop in statin levels (atorvastatin, simvastatin, and metabolites) after extracorporeal LDL-cholesterol elimination (EE) in severe familial hypercholesterolemia (FH). The purpose of this work was to identify the mechanism underlying this drop and its clinical significance as well as to propose measures to optimize a pharmacotherapeutical regimen that can prevent the loss of statins. Methods. Ultra High Performance Liquid Chromatography (UHPLC) connected to the triple quadrupole MS/MS system was used. Patients. A group of long-term treated patients (3–12 years of treatment) with severe FH (12 patients) and treated regularly by LDL-apheresis (immunoadsorption) or haemorheopheresis (cascade filtration) were included in this study. Results. After EE, the level of statins and their metabolites decreased (atorvastatin before/after LDL-apheresis: 8.83/3.46 nmol/l; before/after haemorheopheresis: 37.02/18.94 nmol/l). A specific loss was found (concentration of atorvastatin for LDL-apheresis/haemorheopheresis: 0.28/3.04 nmol/l in washing fluids; 11.07 nmol/l in filters). To prevent substantial loss of statin concentrations, a pharmacotherapeutic regimen with a longer time interval between the dose of statins and EE is recommended (15 hours). Conclusions. A specific loss of statins was found in adsorbent columns and filters. The decrease can be prevented by the suggested dosage scheme

Building A Winning NFL Roster: Best Practices For Sustained Success

The purpose of this capstone is to identify and analyze the factors that contribute to team success in the National Football League through a review of relevant literature, a survey of league personnel, and firsthand experience as a football administrator. This project first studies quantitative data regarding player acquisition, specifically the data behind the NFL entry draft. Next, the current literature regarding off the field processes such as leadership, organizational culture and engagement were reviewed and finally, a two-step Delphi method survey was distributed to a panel of current league professionals. This paper aims to find the most efficient and effective way for teams to acquire players and several ways to optimize that talent based on the best practices researched in organizational culture and leadership

Microbiome Composition and Function in Aquatic Vertebrates: Small Organisms Making Big Impacts on Aquatic Animal Health

Aquatic ecosystems are under increasing stress from global anthropogenic and natural changes, including climate change, eutrophication, ocean acidification, and pollution. In this critical review, we synthesize research on the microbiota of aquatic vertebrates and discuss the impact of emerging stressors on aquatic microbial communities using two case studies, that of toxic cyanobacteria and microplastics. Most studies to date are focused on host-associated microbiomes of individual organisms, however, few studies take an integrative approach to examine aquatic vertebrate microbiomes by considering both host-associated and free-living microbiota within an ecosystem. We highlight what is known about microbiota in aquatic ecosystems, with a focus on the interface between water, fish, and marine mammals. Though microbiomes in water vary with geography, temperature, depth, and other factors, core microbial functions such as primary production, nitrogen cycling, and nutrient metabolism are often conserved across aquatic environments. We outline knowledge on the composition and function of tissue-specific microbiomes in fish and marine mammals and discuss the environmental factors influencing their structure. The microbiota of aquatic mammals and fish are highly unique to species and a delicate balance between respiratory, skin, and gastrointestinal microbiota exists within the host. In aquatic vertebrates, water conditions and ecological niche are driving factors behind microbial composition and function. We also generate a comprehensive catalog of marine mammal and fish microbial genera, revealing commonalities in composition and function among aquatic species, and discuss the potential use of microbiomes as indicators of health and ecological status of aquatic ecosystems. We also discuss the importance of a focus on the functional relevance of microbial communities in relation to organism physiology and their ability to overcome stressors related to global change. Understanding the dynamic relationship between aquatic microbiota and the animals they colonize is critical for monitoring water quality and population health

Accession Site Does Not Influence the Risk of Stroke after Diagnostic Coronary Angiography or Intervention: Results from a Large Prospective Registry

INTRODUCTION: Periprocedural stroke represents a rare but serious complication of cardiac catheterization. Pooled data from randomized trials evaluating the risk of stroke following cardiac catheterization via transradial versus transfemoral access showed no difference. On the other hand, a significant difference in stroke rates favoring transradial access was found in a recent meta-analysis of observational studies. Our aim was to determine if there is a difference in stroke risk after transradial versus transfemoral catheterization within a contemporary real-world registry. METHODS: Data from 14,139 patients included in a single-center prospective registry between 2009 and 2016 were used to determine the odds of periprocedural transient ischemic attack (TIA) and stroke for radial versus femoral catheterization via multivariate logistic regression with Firth's correction. RESULTS: A total of 10,931 patients underwent transradial and 3,208 underwent transfemoral catheterization. Periprocedural TIA/stroke occurred in 41 (0.29%) patients. Age was the only significant predictor of TIA/stroke in multivariate analysis, with each additional year representing an odds ratio (OR) = 1.09 (CI 1.05-1.13, p < 0.000). The choice of accession site had no impact on the risk of periprocedural TIA/stroke (OR = 0.81; CI 0.38-1.72, p = 0.577). CONCLUSION: Observational data from a large prospective registry indicate that accession site has no influence on the risk of periprocedural TIA/stroke after cardiac catheterization

Structure of the human NK cell NKR-P1:LLT1 receptor:ligand complex reveals clustering in the immune synapse.

Signaling by the human C-type lectin-like receptor, natural killer (NK) cell inhibitory receptor NKR-P1, has a critical role in many immune-related diseases and cancer. C-type lectin-like receptors have weak affinities to their ligands; therefore, setting up a comprehensive model of NKR-P1-LLT1 interactions that considers the natural state of the receptor on the cell surface is necessary to understand its functions. Here we report the crystal structures of the NKR-P1 and NKR-P1:LLT1 complexes, which provides evidence that NKR-P1 forms homodimers in an unexpected arrangement to enable LLT1 binding in two modes, bridging two LLT1 molecules. These interaction clusters are suggestive of an inhibitory immune synapse. By observing the formation of these clusters in solution using SEC-SAXS analysis, by dSTORM super-resolution microscopy on the cell surface, and by following their role in receptor signaling with freshly isolated NK cells, we show that only the ligation of both LLT1 binding interfaces leads to effective NKR-P1 inhibitory signaling. In summary, our findings collectively support a model of NKR-P1:LLT1 clustering, which allows the interacting proteins to overcome weak ligand-receptor affinity and to trigger signal transduction upon cellular contact in the immune synapse

Lipoprotein-Associated Phospholipase A 2

Objective. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is extensively expressed by advanced atherosclerotic lesions and may play a role in plaque instability. We selected a group of elderly subjects that underwent transcatheter aortic valve implantation (TAVI) or balloon angioplasty (BA) and separated them into two groups, diabetic and nondiabetic, to compare the level of Lp-PLA2 mass between them. Methods. 44 patients aged 79.6±5.6 years with symptomatic severe aortic valve stenosis underwent TAVI (n=35) or BA (n=9). 21 subjects had confirmed type 2 diabetes mellitus. Lp-PLA2 mass was measured using an enzyme-linked immunosorbent assay kit (USCN Life Science, China) before and 3 days after the procedure. Results. Lp-PLA2 mass was significantly elevated in this population (1296±358 ng/mL before TAVI; 1413±268 ng/mL before BA) and further increased after TAVI (1604±437 ng/mL, P<0.01) or BA (1808±303 ng/mL, P<0.01). Lp-PLA2 mass was significantly increased on the diabetic group before these interventions. Conclusion. Lp-PLA2 may be a novel biomarker for the presence of rupture-prone atherosclerotic lesions in elderly patients. Levels of Lp-PLA2 in diabetic patients may accompany the higher amount of small dense LDL particles seen in these subjects

Predicting cleavability of peptide sequences by HIV protease via correlation-angle approach

In designing HIV protease inhibitors as potential drugs for AIDS therapy, knowledge about what peptide sequences in polyproteins are cleavable by HIV proteases is very useful. In this article, based on the formulation that any octapeptide can be uniquely expressed as a 160-dimensional vector and the principle that the similarity of any two such vectors is associated with their correlation angle, a new method is proposed to predict the cleavability of a peptide sequence by HIV-1 and HIV-2 proteases. The average predicted accuracy the new method for the 105 peptide sequences whose cleavability by HIV-1 protease is known is 96/105=9.14%, which is about 8% higher than that by the existing method for the same set of data. A considerably high rate of correct prediction was also obtained when the new method was used to predict the HIV-2 protease-cleaved sites in some proteins.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45081/1/10930_2005_Article_BF01028191.pd

Data Descriptor : A European Multi Lake Survey dataset of environmental variables, phytoplankton pigments and cyanotoxins

Under ongoing climate change and increasing anthropogenic activity, which continuously challenge ecosystem resilience, an in-depth understanding of ecological processes is urgently needed. Lakes, as providers of numerous ecosystem services, face multiple stressors that threaten their functioning. Harmful cyanobacterial blooms are a persistent problem resulting from nutrient pollution and climate-change induced stressors, like poor transparency, increased water temperature and enhanced stratification. Consistency in data collection and analysis methods is necessary to achieve fully comparable datasets and for statistical validity, avoiding issues linked to disparate data sources. The European Multi Lake Survey (EMLS) in summer 2015 was an initiative among scientists from 27 countries to collect and analyse lake physical, chemical and biological variables in a fully standardized manner. This database includes in-situ lake variables along with nutrient, pigment and cyanotoxin data of 369 lakes in Europe, which were centrally analysed in dedicated laboratories. Publishing the EMLS methods and dataset might inspire similar initiatives to study across large geographic areas that will contribute to better understanding lake responses in a changing environment.Peer reviewe