Multiple Myeloma in the Era of Novel Agents and Stem Cell Therapies

The recent availability of several lines of novel therapeutic agents such as immunomodulatory agents, proteasome inhibitors, and monoclonal antibodies; the widespread utilization of hematopoietic stem cell transplantation; the use of advanced diagnostic techniques that allow risk stratification and monitoring of treatment responses; and the general improvement in health care have revolutionized treatment of patients with multiple myeloma and this has translated into significant improvements in survival outcomes. Monitoring of minimal residual disease can guide the intensity of treatment, and the efficient application of modern diagnostic tools in monitoring treatment responses in real-world clinical practice can hopefully be achieved in the near future. The recent use of quadruplet regimens in the treatment of patients with multiple myeloma has translated into unprecedented treatment responses and survival outcomes. Also, chimeric antigen receptor T-cell therapy and bispecific antibodies represent a new dimension in the precision medicine in MM. Additionally, our ability to induce deep responses has improved, and the treatment goal in myeloma patients tolerating the recommended therapy has moved from delay of disease progression to induction of the deepest possible response

Seasonal variations in scrotal circumference and semen characteristics of Naimi and Najdi rams in Saudi Arabia

In the present study, the authors analysed the effects of seasonal variations on the scrotal circumference and semen characteristics in two ram breeds in Saudi Arabia, namely Naimi and Najdi. Five rams of each breed were used in this experiment. Scrotal circumference and semen characteristics were evaluated in each ram twice a month throughout the year. Significant differences were observed in the scrotal circumference between various seasons. The largest production of semen was recorded mainly in spring, whereas the lowest semen volume was produced in summer. The pH of the semen was slightly alkaline and significantly lower in autumn than in spring. Furthermore, the highest value of the total number of sperm per ejaculate was observed in spring for both breeds. The results indicated that mass motility increased significantly in autumn compared with winter, spring, and summer. Progressive motility was significantly lower during the months of summer and spring. However, no significant differences were recorded between autumn and winter. Hence, the presence of significant seasonal variations in semen quantity and quality of Naimi and Najdi rams suggests the viability of increased utilization of rams in spring and autumn for semen collection and reproductive practices.Keywords: Mass motility, progressive motility, semen volume, sperm concentratio

Outpatient Autologous Hematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma

Autologous hematopoietic stem cell transplantation is still the standard of care in patients with multiple myeloma who are eligible for transplantation, despite the recent availability of several lines of novel therapies. Several studies have shown that autologous transplantation using non-cryopreserved stem cells is safe, cost-effective, and leads to outcomes that are equivalent to transplantation of cryopreserved autologous stem cells. With daily clinical evaluation and intensive supportive care, performance of autologous stem cell transplantation at outpatient setting is safe, feasible, and cost-effective. However, there are specific inclusion and exclusion criteria that should be taken into consideration to select the right candidates for this modality of transplantation. Recipients of outpatient transplantation may require hospitalization in case of certain complications, such as febrile neutropenia, sepsis, decrease in performance status, and severe mucositis. Following outpatient autologous transplantation, maintenance therapy is usually given till disease progression

An Update on Hematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma

Over the past two decades, treatment of multiple myeloma (MM) has advanced dramatically. However, despite the introduction of several lines of novel therapeutics, autologous hematopoietic stem cell transplantation (HSCT) followed by maintenance therapy is the current standard of care in transplant eligible patients. Autologous HSCT can be performed with or without cryopreservation with equivalent short-term and long-term outcomes. In patients with MM, performance of autologous HSCT at outpatient setting is safe, feasible and has a number of advantages such as saving hospital beds and reducing treatment costs. Autologous HSCT can be safely performed in patients with MM having renal dysfunction or failure although particular attention should be made to the timing of administering medications and stem cells with respect to hemodialysis and dose reduction of specific medications according to creatinine clearance. Tandem autologous HSCT is of value in younger patients with adverse cytogenetics and extramedullary disease. Allogeneic HSCT is the only potentially curative therapeutic modality in MM, but it can only be performed in a small fraction of highly selected patients due to the relatively high treatment-related morbidity and mortality. Despite its valuable role in the treatment of MM, autologous HSCT has its own short-term as well as long-term complications

Complicated septic shock caused by Achromobacter xylosoxidans bacteremia in a patient with acute lymphoblastic leukaemia

Infections caused by Achromobacter xylosoxidans cause significant morbidity and mortality in debilitated individuals. Eradication of these infections requires prolonged therapy with antimicrobial agents and removal of any infected central venous catheter. The outcome is usually poor in patients with high risk malignancy, septic complications, and/or multi-organ dysfunction

Tracking and re-finding printed material using a personal digital library

Most web searches aim to re-find previously known information or documents. Keeping track of one’s digital and printed reading material is known to be a challenging and costly task. We describe the design, implementation and evaluation of our Human-centred workplace (HCW) – a system that supports the tracking of physical document printouts. HCW embeds QR codes in the document printout, stores the documents in a personal Digital Library, and uses cameras in the office to track changes in the document locations. We explored the HCW in three evaluations, using the system over several weeks in an office setting, a user study in a lab environment, and extensive functional tests

Deletion and Functional Analysis of Hepatitis B Virus X Protein: Evidence for an Effect on Cell Cycle Regulators

Background/Aims: The hepatitis B virus X protein (HBx) is a viral trans-activator that plays a crucial role in pathogenesis of hepatocellular carcinoma (HCC) via an unknown mechanism. The role of HBx in modulating cell proliferation and programmed cell death is replete with controversies. Thus, the goal of this study was to elucidate the effect of HBx and its deletion mutants on cell cycle progression in human hepatoma cells. Methods: Huh7 cells transfected with either full-length or truncated HBx were tested for their mitogenic potential based on their effect on the expression of key cell cycle-related proteins (p27, cyclin D1, p21, and p53) and pro-apoptotic proteins such as cleaved poly (ADP-ribose) polymerase (PARP) and Bax. Western blotting and immunofluorescence techniques were applied to detect changes in the expression levels and intracellular localization, respectively, of the investigated proteins. Also, Quantitative real-time PCR (qRT-PCR) was used to detect changes in RNA levels. Results: An increased anchorage-independent growth of cells transfected with HBx-WT and its deletion mutants was observed. The cell cycle regulatory molecules were differentially modulated by full-length HBx (1-154) and its different N- and C-terminal truncated forms (HBx (31-154), HBx (61-154), HBx (1-94), and HBx (61-124)). An enhanced modulation of p27, p21, and cyclin D1 was associated with HBx (1-154), whereas p53 expression was significantly inhibited by HBx (61-124). Similarly, the expression of cleaved PARP and Bax was efficiently suppressed by HBx (1-94) and HBx (61-154). Conclusion: The HBx-WT and its mutants play a critical role in the pathogenesis and progression of HCC by modulating cell cycle regulatory proteins

Sliding wear investigation of suspension sprayed WC-Co nanocomposite coatings.

Sliding wear evaluation of nanostructured coatings deposited by Suspension High Velocity Oxy-Fuel (S-HVOF) and conventional HVOF (Jet Kote (HVOF-JK) and JP5000 (HVOF-JP)) spraying were evaluated. S-HVOF coatings were nanostructured and deposited via an aqueous based suspension of the WC-Co powder, using modified HVOF (TopGun) spraying. Microstructural evaluations of these hardmetal coatings included X-ray Diffraction (XRD) and Scanning Electron Microscopy (SEM) equipped with Energy Dispersive X-ray Spectroscopy (EDX). Sliding wear tests on coatings were conducted using a ball-on-flat test rig against steel, silicon nitride (Si3N4) ceramic and WC-6Co balls. Results indicated that nanosized particles inherited from the starting powder in S-HVOF spraying were retained in the resulting coatings. Significant changes in the chemical and phase composition were observed in the S-HVOF coatings. Despite decarburization, the hardness and sliding wear resistance of the S-HVOF coatings was comparable to the HVOF-JK and HVOF-JP coatings. The sliding wear performance was dependent on the ball-coating test couple. In general a higher ball wear rate was observed with lower coating wear rate. Comparison of the total (ball and coating) wear rate indicated that for steel and ceramic balls, HVOF-JP coatings performed the best followed by the S-HVOF and HVOF-JK coatings. For the WC-Co ball tests, average performance of S-HVOF was better than that of HVOF-JK and HVOF-JP coatings. Changes in sliding wear behavior were attributed to the support of metal matrix due to relatively higher tungsten content, and uniform distribution of nanoparticles in the S-HVOF coating microstructure. The presence of tribofilm was also observed for all test couples