Review on special emphasis of bortezomib on relapsed/refractory myeloma

Refractory or relapsed Multiple Myeloma (MM) is a plasma cell neoplasia characterized by paraproteins in the urine or serum and a bone marrow plasmacytosis of over 10%. Multiple/refractory myeloma is a neoplasm of plasma cells and exact cause of multiple myeloma is remain unidentified, it is characterized by accumulation of malignant plasma cells in the bone marrow, leading to bone marrow failure, anemia, skeletal destruction, renal failure, increased susceptibility to infection and hypercalcemia. The survival time for the patients with refractory or multiple myeloma can be prolonged with treatment of newer and more target specific approach. The proteasome inhibitors are an important class of anti-myeloma drugs that have efficacy to disrupt the proteolytic structure of tumor cells and enhancing their susceptibility to apoptosis. Bortezomib has a significant clinical efficacy against refractory multiple myeloma. Bortezomib is the most commonly used and clinically tested proteasome inhibitor and which is effective in prolonging the overall survival in several trials. Bortezomib combinations with other drugs such as dexamethasone and cyclophosphamide are the choice of treatment for standard risk patients following the mSMART guidelines. The success with lower dosage of bortezomib in elderly patient’s proven efficacious subcutaneous usage and its useful proteasome inhibitor to enhance patient’s compliance and reduces toxicity and costs of therapy. This review discusses on special emphasis of bortezomib on relapsed/refractory multiple myeloma as front-line treatment.

A Rare Metastasis to the Bladder

Primary bladder cancer is the fifth most common malignancy but secondary malignancies of the bladder are rare. Distinguishing primary adenocarcinomas of the bladder from secondary adenocarcinomas is difficult and relies on immunohistochemical staining. Prostate, colorectal, breast, and lung all can produce metastatic adenocarcinomas to the bladder. Further management of the malignancy varies depending on the source, thus making proper diagnosis critical. We present only the fifth documented case of metastatic adenocarcinoma of the lung to bladder and performed a review of the literature

Numerical Optimization of a Premixer for an Internal Combustion Engine using Producer Gas as a Fuel

269-275Gasification seems to be one of the sustainable green energy solutions to fulfill the current and future energy needs. For efficient utilization of producer gas on existing IC Engines, carburetor/premixer needs to be carefully designed and developed to achieve uniform mixing quality. A long radius nozzle type premixer has been designed for natural gas engine to be operated on producer gas as an alternate fuel. Different configurations of T – Type premixers with single air entry and twin air entry with different throat diameters and hole sizes are numerically analysed using ANSYS® CFX. Turbulence is modelled using RNG k - ε closure model. Mixer performance is compared in terms of constituents’ mass fraction, flow Uniformity Index (UI) and pressure penalty. Numerical analysis reveals that throat diameter, air entry type and air hole diameter governs mixing and pressure drop. Out of all configurations, twin air entry type premixer provides better mixing of producer gas and air. The optimized design of premixer shows that the absolute deviation in mass fraction of individual constituent lies in the range of ± 1.73% with respect to the actual mass fractions obtained. The average absolute deviation calculated is 1.37% with Uniformity Index 0.958 at the exit plane while the pressure drop across the premixer is 951 Pa

A project for future life—Swedish women's thoughts on childbearing lacking experience of giving birth and parenthood

A lifeworld hermeneutic approach was used in order to understand Swedish women's thoughts on childbearing. Nine women were interviewed, and they ranged in age from 22 to 28 years and represented diverse socioeconomic, educational, sexual, and fertility backgrounds. All women were similar in that they lacked experience of giving birth and parenthood. The analysis showed that childbearing includes dimensions of both immanence and transcendence. Immanence, as childbearing is seen as stagnant to women's freedom in present life. Transcendence, as childbearing is thought of as a project for future life, a part of female identity, and a conscious standpoint for which the woman wants to be prepared and for which she wants to create the best conditions

Temporal Changes in Extracellular Vesicle Hemostatic Protein Composition Predict Favourable Left Ventricular Remodeling after Acute Myocardial Infarction

The subset of plasma extracellular vesicles (EVs) that coprecipitate with low-density lipoprotein (LDL-EVs) carry coagulation and fibrinolysis pathway proteins as cargo. We investigated the association between LDL-EV hemostatic/fibrinolysis protein ratios and post-acute myocardial infarction (post-AMI) left ventricular (LV) remodeling which precedes heart failure. Protein concentrations of von Willebrand factor (VWF), SerpinC1 and plasminogen were determined in LDL-EVs extracted from plasma samples obtained at baseline (within 72 h post-AMI), 1 month and 6 months post-AMI from 198 patients. Patients were categorized as exhibiting adverse (n = 98) or reverse (n = 100) LV remodeling based on changes in LV end-systolic volume (increased or decreased ≥15) over a 6-month period. Multiple level longitudinal data analysis with structural equation (ML-SEM) model was used to assess predictive value for LV remodeling independent of baseline differences. At baseline, protein levels of VWF, SerpinC1 and plasminogen in LDL-EVs did not differ between patients with adverse versus reverse LV remodeling. At 1 month post-AMI, protein levels of VWF and SerpinC1 decreased whilst plasminogen increased in patients with adverse LV remodeling. In contrast, VWF and plasminogen decreased whilst SerpinC1 remained unchanged in patients with reverse LV remodeling. Overall, compared with patients with adverse LV remodeling, higher levels of SerpinC1 and VWF but lower levels of plasminogen resulted in higher ratios of VWF:Plasminogen and SerpinC1:Plasminogen at both 1 month and 6 months post-AMI in patients with reverse LV remodeling. More importantly, ratios VWF:Plasminogen (AUC = 0.674) and SerpinC1:Plasminogen (AUC = 0.712) displayed markedly better prognostic power than NT-proBNP (AUC = 0.384), troponin-I (AUC = 0.467) or troponin-T (AUC = 0.389) (p \u3c 0.001) to predict reverse LV remodeling post-AMI. Temporal changes in the ratios of coagulation to fibrinolysis pathway proteins in LDL-EVs outperform current standard plasma biomarkers in predicting post-AMI reverse LV remodeling. Our findings may provide clinical cues to uncover the cellular mechanisms underpinning post-AMI reverse LV remodeling

First time pregnant women's experiences in early pregnancy

Background: There are few studies focusing on women's experiences of early pregnancy. Medical and psychological approaches have dominated the research. Taking women's experiences seriously during early pregnancy may prevent future suffering during childbirth. Aim: To describe and understand women's first time experiences of early pregnancy. Method: Qualitative study using a phenomenological hermeneutic approach. Data were collected via tape-recorded interviews in two antenatal care units in Sweden. Twelve first time pregnant women in week 10–14, aged between 17 and 37 years participated. Results: To be in early pregnancy means for the women a life opening both in terms of life affirming and suffering. The central themes are: living in the present and thinking ahead, being in a change of new perspectives and values and being in change to becoming a mother. Conclusions: The results have implications for the midwife's encounter with the women during pregnancy. Questions of more existential nature, instead of only focusing the physical aspects of the pregnancy, may lead to an improvement in health condition and a positive experience for the pregnant woman

Defining the characteristics and expectations of fluid bolus therapy: a worldwide perspective

Purpose: The purpose of the study is to understand what clinicians believe defines fluid bolus therapy (FBT) and the expected response to such intervention. Methods: We asked intensive care specialists in 30 countries to participate in an electronic questionnaire of their practice, definition, and expectations of FBT. Results: We obtained 3138 responses. Despite much variation, more than 80% of respondents felt that more than 250 mL of either colloid or crystalloid fluid given over less than 30 minutes defined FBT, with crystalloids most acceptable. The most acceptable crystalloid and colloid for use as FBT were 0.9% saline and 4% albumin solution, respectively. Most respondents believed that one or more of the following physiological changes indicates a response to FBT: a mean arterial pressure increase greater than 10 mm Hg, a heart rate decrease greater than 10 beats per minute, an increase in urinary output by more than 10 mL/h, an increase in central venous oxygen saturation greater than 4%, or a lactate decrease greater than 1 mmol/L. Conclusions: Despite wide variability between individuals and countries, clear majority views emerged to describe practice, define FBT, and identify a response to it. Further investigation is now required to describe actual FBT practice and to identify the magnitude and duration of the physiological response to FBT and its relationship to patient-centered outcomes.Facultad de Ciencias Médica