Mohammad Shamiea, Martin H Ellis, Michael Lishner and Osnat Jarchowsky Dolberg*
Published on: 25th June, 2024
Carfilzomib, a highly selective proteasome inhibitor, is commonly used in the treatment of multiple myeloma and AL amyloidosis. While its efficacy is well-established, there is increasing recognition of its association with cardiovascular adverse events, including hypertension, heart failure, and arrhythmias. However, cases of carfilzomib-induced pericardial disease remain rare. Here, we present a case of a 78-year-old female with multiple myeloma who experienced two episodes of hemorrhagic pericardial effusion following carfilzomib therapy, highlighting the importance of vigilant cardiovascular monitoring during treatment.
Stem cell treatments depend not only on the type of cell to be used but also on the different implantation techniques. Intravascular cell injections are known to rapidly separate from the vessels. On the other hand, it is also well known that direct injection into the myocardium provides better coupling within the heart muscle. That were the cases of Embriofetal stem cell (HFDSC) or Autologous stem cells (ABMSC) in our experience focused on direct approaches.
Between 2003 and 2011, 17 patients with heart failure were treated with stem cells as part of our Foundation’s Regenerative Medicine program. In several centers and countries 4 with ischemic cardiomyopathy of which 3 were surgically implanted with autologous bone marrow stem cells (ABMSC) plus bypass surgery. One patient was treated with hyperbaric medicine plus bypass surgery. Patients with idiopathic cardiomyopathy were implanted surgically with 2 different types of stem cells. Ten patients were implanted with stem cells derived from human fetuses (HFDSCs) and three patients with autologous bone marrow stem cells (ABMSC). The ejection fractions of the coronary artery bypass graft off pump OPCAB (control group) versus coronary artery bypass group off pump OPCAB plus stem cell transplantation were as followsin the entire serie: preoperative, 30.7% +/- 2.5% compared to 29.4% +/- 3.6%; 1 month, 36.4% +/- 2.6% versus 42.1% +/- 3.5%; 3 months, 36.5% +/- 3.0% vs. 45.5% +/- 2.2%; And 6 months, 37.2% +/- 3.4% versus 46.1% +/- 1.9% (p <0.001). The first patient performed at our center in Argentina in this series is alive and asymptomatic 15 years after implantation, and the rest of this series we do not have current data. A patient without visible vessels in the anterior wall of the left ventricle was treated with 18 hyperbaric chamber sections from one hour at 1.4 AT. After creating angiogenesis, the patient was operated on receiving 2 grafts (mammary and venous) without extracorporeal circulation in the anterior descending artery and diagonal artery. The preoperative ejection fraction was 33% at 90 months of follow up the ejection fraction was 58%. The patient at 90 months was asymptomatic. Of the idiopathic heart disease group, nine patients underwent median sternotomy, and received human fetal stem cells (HFDSCs from ectopic pregnancy or spontaneous abortion, three patients received autologous bone marrow stem cells ABMSC) and 1HFDSCs for Minimally Invasive Surgery.
Patients with HFDSC, compared to baseline, improved: The mean (±SD) NYHA class decreased from 3.4 ± 0.5 to 1.33 ± 0.5 (P = 0.001); Mean EF increased 31%, from 26.6% ± 4.0% to 34.8% ± 7.2% (p = 0.005); the yield in ETT increased 291.3%, from 4.25 minutes to 16.63 minutes (128.9% in metabolic equivalents, 2.45 to 5.63) (P <0.0001); the mean LVEDD decreased 15%, from 6.85 ± 0.6cm to 5.80 ± 0.58cm (P <0.001); the mean performance on the 6-minute walk test increased 43.2%, from 251 ± 113.1 seconds to 360 ± 0 seconds (P = 0.01); the mean distance increased 64.4%, from 284.4 ± 144.9m to 468.2 ± 89.8m (P = 0.004); and the mean score in the Minnesota congestive HF test decreased from 71 ± 27.3 to 6 ± 5.9 (p <0.001). Kaplan-Maier’s probability of survival at 40 months was 66%. No rejection or cancer was observed at follow-up, in this series follow-up was discontinued at 4 years. In idiopathic patients receiving autologous cells by Mininvasive technique preoperative NYHA was 3.6 (+/- 0.70) 6 months after receiving stem cell therapy. The mean value of the functional class was 1.9 (+/- 0.90) (p <0.005). ) showing marked clinical improvement. The preimplantation ejection fraction was 28% (+/- 3.6%) and at 6 months 44% (+/- 4.7%) (p <0.005). There was a similar change in ventricular diameters: After 6 months LVESV went from 50mm (+/- 3.3) to 42mm (+/- 4.5) (p <0.05). Two of the three patients in this group received re-synchronization therapy; one died at 10 years and 4 months, another at age 11 and another one alive at 12 years of the implant. More experience should be performed with different techniques and cells to find the appropriate treatment in this type of patients.
Today’s need for renewable energy combined with modern societies' reliability on on-demand power leads us to find solutions that can store excess or produce directly to storage for later use. A MOlecular Solar Thermal (MOST) based on norbornadiene/quadricyclane(NBD/QC) does the latter with an isomeric photoswitching molecule pair. The theoretical studies of molecular solar thermals (MOST) provide a needed understanding of potential synthetic candidates. We have investigated an array of more complex solvation models for the norbornadiene/quadricycle (NBD/QC) photoswitch and the impacts of the models on the first absorption energy. Our results have been obtained with various density functional theoretical methods and basis sets.
Molecular interactions between proteins or between proteins and small molecules are pivotal events for selective binding of biological structures and, consequentially, for their correct function. In this scenario, the evaluation of kinetic parameters, characterizing a molecular interactions, is considered a crucial event to reveal the nature of binding processes.
The focus on peculiar forces involved in the molecular recognition represents an opportunity to explore biological interactions in real time, and to develop a number of innovative biotechnological methods for diagnosis and/or therapy.
Currently, optical biosensors, offering an increasingly effective technology to detect in real time molecular binding, are usually composed by a detector, a sensor surface and a sample delivery system: only definite substances, which are able to interact specifically with the biological part, lead to an optical or electrical signal of the physical transducer.
In this review we want to highlight the exponentially-growing interest of Surface Plasmon Resonance (SPR) based optical biosensors for molecular binding analysis in different research fields.
Mitochondria are essential intracellular organelles that significantly influence various cellular processes, including metabolism, stress response, and cell fate. Their precise regulation is crucial for maintaining both organelle and cellular homeostasis. Wound healing is a complex, multifactorial process that relies on the coordinated actions of multiple cell types and numerous cellular mechanisms. Dysregulation in this process can lead to chronic wounds, which pose substantial challenges for healthcare systems and present limited treatment options due to their intricate pathogenesis. Recent research has increasingly focused on the role of mitochondria in wound healing, revealing their involvement in critical processes such as metabolism, apoptosis, and redox signaling. Mitochondrial dynamics play a vital role in wound healing by adapting to cellular demands and environmental cues. Moreover, mitophagy, the selective degradation of damaged mitochondria, is crucial for maintaining mitochondrial integrity and function during the healing process. Mitochondria are not only pivotal in energy production but also in calcium homeostasis and the generation of mitochondrial reactive oxygen species, which are essential for signaling during wound repair. As wound healing progresses through distinct yet overlapping stages mitochondria facilitate the energy demands of repair and contribute to cytoskeletal remodeling necessary for wound closure. Understanding the multifaceted roles of mitochondria in wound healing could lead to novel therapeutic approaches for chronic wounds. Future research should prioritize investigating mitochondrial dynamics and functions in human tissues to develop targeted strategies for enhancing wound healing outcomes.
Background: Varicocele therapy is a controversial issue. No single approach is adopted as the best therapeutic option. Testes get blood supply from testicular artery, cremasteric artery and artery to the vas deference. So ligation of testicular artery in the abdomen do not cause ischemia to the testis. This was already demonstrated in many studies. Classical Palomo varicocelectomy also consists of open ligation of testicular vessels in the retroperitoneum. En mass ligation of testicular vein and artery is technically easy and fast in laparoscopic varicocelectomy (LV). Chance of missing some veins are also less. Henceforth recurrence is also less. Recurrence and post-operative complications are high when only testicular vein is ligated by laparoscopy in the retroperitoneum. We wanted to see the outcome of laparoscopic varicocelectomy by mass ligation technique.
Methods: 56 patients of symptomatic varicoceles were included in the study from the outpatient services. Symptomatic varicoceles of grade 2 to grade 3 were operated from January 2012 till January 2019 over a period of 7(seven) years in Jahurul Islam Medical college Hospital. The patients were selected for dull pain and ugly veins not for infertility. All were operated by laparoscopy with en-mass ligation of testicular vein and artery in the retroperitoneum. They were followed up for a period of six months after surgery. We collected all the data in a retrospective manner.
Results: The average operation time was 27±3 minutes. Average post-operative hospital stay was 32±7 hours. There were no technical failures requiring conversion to open varicocelectomy. There was no incidence of hydrocele formation nor testicular atrophy. One patient of bilateral varicocele had 50% reduction of his varicocele. We considered this a recurrence. All other patient had complete reduction of varicocele. One patient developed hemo-peritoneum due to dislodgement of hemo-clip, which required laparotomy. He did not require any further surgery for his varicocele.
Conclusion: Laparoscopic varicocelectomy with mass ligation technique is safe, effective, less time consuming and easy to perform. Recurrence and post-operative complications are minimum. Plastic hemo-lock should be used rather than titanium heom-clip for ligation of testicular vessels. There is no incidence of testicular atrophy or any adverse effect on testis.
This paper analyses the effect of virtual reality visualization (VRV) on climbers, with respect to the traditional visualization methodology. The study sample was made up of 21 novel climbers: Control Group CG (N=7), Traditional Visualization Group TVG (N=7) and Virtual Reality Group VRG (N=7). In order to implement the mental imagery through virtual reality, a 360º Ricoh Theta S camera and a pair of Woxter Neo VR1 goggles were used. The data analysis was carried out with a simple ANOVA of three means. No statistically significant differences were found. The results are discussed and future lines of research are established.
Isabella Sforzin*, Juliana Rodrigues Beal and Fernando Moura
Published on: 27th June, 2024
Non-small-cell lung cancer (NSCLC) accounts for 85% of lung cancer cases and is associated with different risk factors (smoking habits, gender, and age). In this scenario, many studies have been conducted to pursue improvement of survival, faster and better therapy response, reduced adverse events, and expanded available therapies and treatments against tumor resistance to drugs. These studies have focused on defining the most prevalent NSCLC biomarkers (EGFR, HER2, ALK, MET, ROS1, BRAF, KRAS G12C, HER3, NTRK, and NRG1) and their actionability. It is noteworthy that expressed kinase receptors can have overlapping mechanisms of activation of different pathways (JAK-STAT, MAPK, PI3K-AKT-mTOR, and PLC-c), which can lead to the same outcome of cell proliferation, migration, and survival resulting in increased tumor resistance to treatment. This review provides an overview of the latest findings regarding NSCLC treatment, emphasizing particular biomarkers and potential molecularly altered pathways implicated as targeted therapies. Additionally, it explores the clinical significance of the proposed treatments, their implication on progression-free survival, ongoing clinical trials, and their perspective of evolution so far.
Forebrain GABAergic neurons, the main inhibitory type of neuron in the cortex and hippocampus, represent a highly heterogeneous cell population that has been implicated in the predisposition to epilepsy and the onset of seizure. Earlier attempts to restore inhibition and reduce seizure in animal models of epilepsy have been carried out using embryonic basal forebrain tissue as source of immature GABAergic progenitors in cell-based therapies, with promising results. For therapeutic strategies this approach appears unrealistic, while the use of pluripotent stem cells to obtain immature GABAergic neurons opens new and promising avenues. Research on neural stem cells and pluripotent stem cells has greatly advanced and protocols have been established to efficiently direct progenitor cells to differentiate towards the GABAergic lineage. However, being highly heterogeneous, these neurons are difficult to be fully represented in vitro. Better knowledge on the expressed gene profiles, at single cell level, and the differentiation trajectory of these neurons will consent a more precise monitoring of the differentiation steps. Here we review the current literature about how to obtain and characterize genuine inhibitory neurons, how these can be grafted in animal models (and one day possibly in human) and which diseases could potentially be targeted and the efficiency of therapeutic outcome. The main obstacles that need to be overcome are: a) choice of an appropriate animal model, b) availability of human cells prone to GABA differentiation, c) the full representation of all IN subtypes, their proportions and their physiological activities, d) how to monitor them on the long-term after transplant.
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