Mantle Cell Lymphoma: Current Concepts

Mantle Cell Lymphoma is a rare B-cell malignancy that can invade almost any structure in the body and recur after short-lived clinical responses. The pathogenesis and clinical features are well defined, but management has not yet been optimized. Induction with traditional immune-chemotherapy regimens that are used in other nonHodgkin lymphomas rarely generate durable remissions. Therefore, clinical research is needed to improve treatment of de novo disease and to establish safe and effective regimens for maintenance and salvage options for relapsed or refractory disease. This comprehensive review discusses disease pathogenesis and focuses on emerging treatment paradigms using novel targeted therapies

A Point Mutation in DNA Polymerase β (POLB) Gene Is Associated with Increased Progesterone Receptor (PR) Expression and Intraperitoneal Metastasis in Gastric Cancer

Increased expression of progesterone receptor (PR) has been reported in gastric cancer (GC). We have previously identified a functional T889C point mutation in DNA polymerase beta (POLB), a DNA repair gene in GC. To provide a detailed analysis of molecular changes associated with the mutation, human cDNA microarrays focusing on 18 signal transduction pathways were used to analyze differential gene expression profiles between GC tissues with T889C mutant in POLB gene and those with wild type. Among the differentially expressed genes, notably, PR was one of the significantly up-regulated genes in T889C mutant POLB tissues, which were subsequently confirmed in POLB gene transfected AGS cell line. Interestingly, patients with T889C mutation and PR positivity were associated with higher incidence of intraperitoneal metastasis (IM). In vitro studies indicate that PR expression was upregulated in AGS cell line when transfected with T889C mutant expression vector. Cotransfection of T889C mutant allele and PR gene induced cell migration in the cell line. These data demonstrated that T889C mutation-associated PR overexpression results in increased IM. Therefore, T889C mutation-associated PR overexpression may serve as a biomarker for an adverse prognosis for human GC

Restless leg syndrome in multiple sclerosis: a case–control study

ObjectivesThis study assessed the prevalence of restless leg syndrome (RLS) among patients with multiple sclerosis (pwMS) and the association between RLS and MS disease duration, sleep disturbance, and daytime fatigue.MethodsIn this cross-sectional study, we interviewed 123 patients via phone calls using preset questionnaires containing the International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria, Pittsburgh Sleep Quality Index (PSQI), and Fatigue Severity Scale (FSS) diagnostic criteria validated in both Arabic and English. The prevalence of RLS in MS was compared to a group of healthy controls.ResultsThe prevalence of RLS in pwMS, defined by meeting all four requirements included in the IRLSSG diagnostic criteria, was 30.3% compared to 8.3% in the control group. About 27.3% had mild RLS, 36.4% presented with moderate, and the remaining had severe or very severe symptoms. Patients with MS who experience RLS had a 2.8 times higher risk of fatigue compared to pwMS without RLS. pwMS with RLS had worse sleep quality, with a mean difference of 0.64 in the global PSQI score. Sleep disturbance and latency had the most significant impact on sleep quality.ConclusionThe prevalence of RLS among MS patients was significantly higher compared to the control group. We recommend educating neurologists and general physicians to increase their awareness of the increasing prevalence of RLS and its association with fatigue and sleep disturbance in patients with MS

Modulation of cancer cell growth and progression by Caveolin-1 in the tumor microenvironment

Caveolin-1 (Cav-1), a major structural component of cell membrane caveolae, is involved in a variety of intracellular signaling pathways as well as transmembrane transport. Cav-1, as a scaffolding protein, modulates signal transduction associated with cell cycle progression, cellular senescence, cell proliferation and death, lipid homeostasis, etc. Cav-1 is also thought to regulate the expression or activity of oncoproteins, such as Src family kinases, H-Ras, protein kinase C, epidermal growth factor, extracellular signal-regulated kinase, and endothelial nitric oxide synthase. Because of its frequent overexpression or mutation in various tumor tissues and cancer cell lines, Cav-1 has been speculated to play a role as an oncoprotein in cancer development and progression. In contrast, Cav-1 may also function as a tumor suppressor, depending on the type of cancer cells and/or surrounding -stromal cells in the tumor microenvironment as well as the stage of tumors.

Bilateral Chylothorax Due to Blunt Trauma Without Radiographic Evidence of Traumatic Injury

Chylothorax represents an uncommon clinical entity with multiple etiologies. Chylothorax following blunt thoracic trauma is typically associated with posterior rib fractures or thoracic vertebral fractures or dislocations. The occurrence of a traumatic chylothorax in the absence of associated injuries is a rare event. We report a case of a 51-year-old patient who developed bilateral chylothorax after sustaining blunt trauma without radiographic evidence of traumatic injury. A 51-year-old male presented to the emergency department complaining of progressively worsening shortness of breath and associated chest pain for the prior one week following a fall down several concrete steps. On evaluation, the patient was found to have bilateral pleural effusions with no radiographic evidence of traumatic injury, including posterior rib or thoracic vertebral fractures. Subsequent thoracentesis and pleural fluid analysis were performed confirming the diagnosis of chylothorax. Management included repeated thoracentesis, diet modification and octreotide administration, which resulted in dramatic improvement and eventual resolution of symptoms. Non-iatrogenic traumatic bilateral chylothorax in the absence of other radiographically demonstrated bony or soft tissue injury is a rare event. Chylothorax should be considered in the differential diagnosis of patients presenting with chest pain or shortness of breath following blunt trauma and evidence of pleural effusion, even in the absence of obvious traumatic fracture or injury on radiographic imaging

Behavior of FRP-Strengthened RC Beams with Large Rectangular Web Openings in Flexure Zones: Experimental and Numerical Study

Abstract This paper aims to investigate the behavior of fiber reinforced polymer (FRP) strengthened reinforced concrete (RC) beams containing large rectangular web openings in the flexure zone. Studied parameters were type of loading, opening size and strengthening scheme. Seven RC beams categorized into two different groups were tested. In the first group, two unstrengthened beams (one solid without opening and one with large rectangular web opening in the pure flexure zone) were tested under four-point bending. In the second group, five beams were tested under center-point loading. They comprised of one reference solid beam and four beams with large rectangular web opening in the maximum-moment region. Out of the four beams with openings, two specimens were unstrengthened and the other two were strengthened with two different FRP schemes. A numerical study was also conducted and the results of analysis were validated with experiments. The calibrated analysis was then used for some useful parametric studies in which the effect of different parameters was investigated

Applying Transformer Insulation Using Weibull Extended Distribution Based on Progressive Censoring Scheme

In this paper, the Weibull extension distribution parameters are estimated under a progressive type-II censoring scheme with random removal. The parameters of the model are estimated using the maximum likelihood method, maximum product spacing, and Bayesian estimation methods. In classical estimation (maximum likelihood method and maximum product spacing), we did use the Newton–Raphson algorithm. The Bayesian estimation is done using the Metropolis–Hastings algorithm based on the square error loss function. The proposed estimation methods are compared using Monte Carlo simulations under a progressive type-II censoring scheme. An empirical study using a real data set of transformer insulation and a simulation study is performed to validate the introduced methods of inference. Based on the result of our study, it can be concluded that the Bayesian method outperforms the maximum likelihood and maximum product-spacing methods for estimating the Weibull extension parameters under a progressive type-II censoring scheme in both simulation and empirical studies