Novel Treatment Options for Multiple Myeloma.

Multiple myeloma (MM), the second most common hematologic malignancy in the United States, is characterized by repeated cycles of remission and relapse, with increasing resistance to treatment after each line of therapy. Despite the virtually incurable nature of MM, recent therapeutic breakthroughs have fundamentally reshaped its treatment landscape. This review explores evolving care paradigms, spanning from newly diagnosed MM to relapsed or refractory disease.

Allometries of cell and tissue anatomy and photosynthetic rate across leaves of C and C grasses.

Allometric relationships among the dimensions of leaves and their cells hold across diverse eudicotyledons, but have remained untested in the leaves of grasses. We hypothesised that geometric (proportional) allometries of cell sizes across tissues and of leaf dimensions would arise due to the coordination of cell development and that of cell functions such as water, nutrient and energy transport, and that cell sizes across tissues would be associated with light-saturated photosynthetic rate. We tested predictions across 27 globally distributed C and C grass species grown in a common garden.

Inhibition of SRC-mediated integrin signaling in bone marrow niche enhances hematopoietic stem cell function.

Interaction with microenvironmental factors is crucial for the regulation of hematopoietic stem cell (HSC) function. Stroma derived factor (SDF)-1α supports HSCs in the quiescent state and is central to the homing of transplanted HSCs. Here, we show that integrin signaling regulates expression transcriptionally.

Recreational drug toxicity with severe hyperthermia: Rapid onsite treatment and clinical course.

Electronic dance music festivals have gained notoriety in the critical care and emergency medicine fields due to an alarming incidence of hospitalizations and deaths related to the high prevalence of recreational drug use. Recreational drug use toxicity, in part related to sympathomimetic toxidromes, may cause hyponatremia, seizures, rhabdomyolysis, hyperkalemia, acidosis, coagulopathy, circulatory shock, multi-organ failure, and even death. This wide-ranging syndrome has been referred to as psychostimulant drug-induced toxicity.

Status of precision medicine approaches to traumatic brain injury.

Traumatic brain injury (TBI) is a serious condition in which trauma to the head causes damage to the brain, leading to a disruption in brain function. This is a significant health issue worldwide, with around 69 million people suffering from TBI each year. Immediately following the trauma, damage occurs in the acute phase of injury that leads to the primary outcomes of the TBI.

Prehospital Tibial Intraosseous Drug Administration is Associated with Reduced Survival Following Out of Hospital Cardiac Arrest: A study for the CARES Surveillance Group.

Background: Recent reports have questioned the efficacy of intraosseous (IO) drug administration for out-of-hospital cardiac arrest (OHCA) resuscitation. Our aim was to determine whether prehospital administration of resuscitative medications via the IO route was associated with lower rates of return of spontaneous circulation (ROSC) and survival to hospital discharge than peripheral intravenous (IV) infusion in the setting of OHCA.

Methods: We obtained data on all OHCA patients receiving prehospital IV or IO drug administration from the three most populous counties in Michigan over three years.

APOE4 genetic polymorphism results in impaired recovery in a repeated mild traumatic brain injury model and treatment with Bryostatin-1 improves outcomes.

After traumatic brain injury (TBI), some people have worse recovery than others. Single nucleotide polymorphisms (SNPs) in Apolipoprotein E (APOE) are known to increase risk for developing Alzheimer's disease, however there is controversy from human and rodent studies as to whether ApoE4 is a risk factor for worse outcomes after brain trauma. To resolve these conflicting studies we have explored the effect of the human APOE4 gene in a reproducible mouse model that mimics common human injuries.

Quantum Diffie-Hellman Extended to Dynamic Quantum Group Key Agreement for e-Healthcare Multi-Agent Systems in Smart Cities.

Multi-Agent Systems can support e-Healthcare applications for improving quality of life of citizens. In this direction, we propose a healthcare system architecture named smart healthcare city. First, we divide a given city into various zones and then we propose a zonal level three-layered system architecture.

BDNF Val66Met Genetic Polymorphism Results in Poor Recovery Following Repeated Mild Traumatic Brain Injury in a Mouse Model and Treatment With AAV-BDNF Improves Outcomes.

Clinicians have long noticed that some Traumatic Brain Injury (TBI) patients have worse symptoms and take a longer time to recover than others, for reasons unexplained by known factors. Identifying what makes some individuals more susceptible is critical to understanding the underlying mechanisms through which TBI causes deleterious effects. We have sought to determine the effect of a single nucleotide polymorphism (SNP) in Brain-derived neurotrophic factor (BDNF) at amino acid 66 (rs6265) on recovery after TBI.

Utility of Magnetic Resonance Imaging Features for Improving the Diagnosis of Idiopathic Intracranial Hypertension Without Papilledema.

Objective: Revised diagnostic criteria for idiopathic intracranial hypertension (IIH) were proposed in part to reduce misdiagnosis of intracranial hypertension without papilledema (WOP) by using 3 or 4 MRI features of intracranial hypertension when a sixth nerve palsy is absent. This study was undertaken to evaluate the sensitivity and specificity of the MRI criteria and to validate their utility for diagnosing IIH in patients with chronic headaches and elevated opening pressure (CH + EOP), but WOP.

Methods: Brain MRIs from 80 patients with IIH with papilledema (WP), 33 patients with CH + EOP, and 70 control patients with infrequent episodic migraine were assessed in a masked fashion for MRI features of intracranial hypertension.

Nrf2 dependent antiaging effect of milk-derived bioactive peptide in old fibroblasts.

Prolonged passaging of primary fibroblast cells totally shapes the natural biological phenomena and leads to the appearance of features related to senescence. As a result, it is a good natural tool to delineate the molecular mechanism of cellular aging. The present investigation revealed the antiaging effect of milk-derived novel bioactive peptide (VLPVPQK).

Interferon-tau stimulated gene expression: A proxy to predict embryonic mortality in dairy cows.

The embryonic mortality in cows is a growing concern for an ever-expanding dairy industry. The current study was an attempt to shorten the open period of dairy cows having suffered embryonic loss by diagnosing them at an earlier stage. The blood samples were collected from the Karan Fries (KF) cows on days 0 (day of AI/estrus), 4, 8, 12, 14, 16, 18, 21, 24, 28, 35 and 42 post insemination.

Nanostructured lipid carriers for site-specific drug delivery.

Nanostructured lipid carriers (NLC), comprises of a blend of solid and liquid lipids which results in a partially crystallized lipid system and imparts many advantages over solid lipid nanoparticles such as enhanced drug loading capacity, drug release modulation flexibility and improved stability. NLC have found numerous applications in both pharmaceutical and cosmetic industry due to ease of preparation, the feasibility of scale-up, biocompatibility, non-toxicity, enhanced targeting efficiency and the possibility of site-specific delivery via various routes of administration. This review highlights the NLC with focus on the structure, the various fabrication techniques used and the characterization techniques which are critical in the development of a suitable and stable formulation.

DoE based Olanzapine loaded poly-caprolactone nanoparticles decreases extrapyramidal effects in rodent model.

The purpose of present investigation was to nano-encapsulate atypical antipsychotic such as Olanzapine in polymeric nanoparticles in order to explore the possibility of minimizing drug associated extrapyramidal adverse effects. The polymeric nanoparticulate systems were prepared using FDA approved polymer, polycaprolactone, by simple technique of nanoprecipitation using factorial design by DoE approach. The significant factors selected for the optimization during formulation development process were polymer content and surfactant concentration at three different levels (3 factorial design).

Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations.

Early preclinical evidence provided the rationale for programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) blockade as a potential form of cancer immunotherapy given that activation of the PD-1/PD-L1 axis putatively served as a mechanism for tumor evasion of host tumor antigen-specific T-cell immunity. Early-phase studies investigating several humanized monoclonal IgG4 antibodies targeting PD-1 and PD-L1 in advanced solid tumors paved way for the development of the first PD-1 inhibitors, nivolumab and pembrolizumab, approved by the Food and Drug Administration (FDA) in 2014. The number of FDA-approved agents of this class is rapidly enlarging with indications for treatment spanning across a spectrum of malignancies.

Antioxidative peptide from milk exhibits antiosteopenic effects through inhibition of oxidative damage and bone-resorbing cytokines in ovariectomized rats.

Objectives: Oxidative stress has been implicated as a crucial pathogenic factor in the development of postmenopausal osteoporosis. Milk-derived antioxidative peptides are gaining much attention toward the development of prodrugs for alleviating several human diseases, including osteoporosis. The aim of the present study was to determine whether antioxidant peptides are good candidates for alleviating postmenopausal osteoporosis.

Variance Reduction in Stochastic Gradient Langevin Dynamics.

Stochastic gradient-based Monte Carlo methods such as stochastic gradient Langevin dynamics are useful tools for posterior inference on large scale datasets in many machine learning applications. These methods scale to large datasets by using noisy gradients calculated using a mini-batch or subset of the dataset. However, the high variance inherent in these noisy gradients degrades performance and leads to slower mixing.

Buffalo casein derived peptide can alleviates HO induced cellular damage and necrosis in fibroblast cells.

Oxidative stress is one of a critical pathogenic factor in the progression of aging and chronic diseases such as cancer, myocardial inflammation and diabetes. In the present scenario, peptides with short half life and more biological specificities are gaining much attention as prodrugs. Thus, the present investigation carried out to screen potential antioxidative peptide, VLPVPQK to cope with the cellular oxidative damage.

Protective effects of casein-derived peptide VLPVPQK against hydrogen peroxide-induced dysfunction and cellular oxidative damage in rat osteoblastic cells.

Oxidative stress inhibits osteoblast differentiation and function that lead to the development of osteoporosis. Casein-derived peptide VLPVPQK (PEP), a potent antioxidant, was isolated from β-casein of buffalo milk. We used an in vitro oxidative stress model induced by hydrogen peroxide (HO) in rat osteoblastic cells to investigate the protective effects of PEP against HO-induced dysfunction and oxidative damage.

Design and in vivo evaluation of solid lipid nanoparticulate systems of Olanzapine for acute phase schizophrenia treatment: Investigations on antipsychotic potential and adverse effects.

The present paper discusses the design, characterization and in vivo evaluation of glyceryl monostearate nanoparticles of Olanzapine, an atypical antipsychotic drug for acute schizophrenia treatment, during which hospitalization is mandatory and adverse effects are at its peak. The solid lipid nanoparticulate system was obtained by emulsification-ultra sonication technique wherein three factors such as solid lipid content, concentration of surfactant and drug: solid lipid ratio were selected at three different levels in order to study their influence on significant characteristic responses such as particle size, encapsulation efficiency and drug content. A Box Behnken design with 17 runs involving whole factors at three levels was employed for the study.

Aloe vera (Aloe barbadensis Miller) supplemented probiotic lassi prevents Shigella infiltration from epithelial barrier into systemic blood flow in mice model.

The aim of present work was to investigate preventive role of orally administered Aloe vera supplemented probiotic lassi (APL) on Shigella dysenteriae infection in mice. At the end of experimental period (2, 5 and 7 days of challenging), different organs such as spleen, liver, small intestine, large intestine, and peritoneal fluid were collected and assessed for Shigella colonization. Secretary IgA was estimated in intestinal fluid.

Effect of buffalo casein-derived novel bioactive peptides on osteoblast differentiation.

Purpose: Epidemiological and intervention studies show that milk consumption in childhood and during adolescence is related to higher bone mineral density. Milk and milk products prevent the bone loss in pre- and postmenopausal women. Apart from calcium, there are other biologically active compounds in milk such as bioactive peptides which may play a role in promoting bone health.

Akt drives buffalo casein-derived novel peptide-mediated osteoblast differentiation.

Milk is a potential nutraceutical with wide range of bioactive compounds that are antioxidative, antimicrobial, antithrombotic, immunomodulatory, opioid and antihypertensive. Various intervention studies with milk reflect its stupendous role in elevating bone mineral density. Milk and milk products have shown a preventive effect in bone loss during pre- and postmenopausal women.

Incidence of mastitis and activity of milk neutrophils in Tharparkar cows reared under semi-arid conditions.

Rearing of indigenous Tharparkar (TP) cows (native of arid Thar deserts) under high humid conditions (>75 % humidity) has increased the incidence of mammary infections in them. A study was undertaken to see the number, activity, and expression of milk neutrophils isolated from healthy and mastitic cows. There was a significant (P < 0.