The effectiveness of antimicrobial photodynamic therapy with prodigiosin against reference strains of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.

Prodigiosin (PG) is a secondary metabolite of bacterial origin that is able to absorb the visible light and plays a role as a photosensitizer in photodynamic therapy (PDT). This in vitro study aimed to investigate the cytotoxicity of PG-mediated PDT against the reference strains of Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of PG were determined. Each strain was then allocated into four groups as follows: G1: control (no treatment), G2: PG-treated groups that received different PG concentrations (1000-1.95 µM), G3: laser-treated group (wavelength: 520 nm, radiation dose: 187 J/cm2), and G4: PG-mediated PDT groups that were initially treated with different concentrations of PG and were then exposed to laser irradiation in the same way as the previous group. Finally, the number of colony-forming units per milliliter (CFU/mL) was calculated and analyzed using the SPSS software. PG had both bacteriostatic and bactericidal activities on the tested bacteria, with the maximum antibacterial effect being observed against S. aureus. In all bacterial strains, the maximum number of CFUs was observed in the control group followed by the laser-irradiated and PG-treated groups, but the differences were not statistically significant (p > 0.05). However, the utilization of PG-mediated PDT resulted in a significant decrease in the mean number of CFUs in all the tested bacteria (p < 0.0001). PG-mediated PDT had the potential to kill some bacterial strains in the laboratory. Yet, further studies are warranted to confirm its efficacy and safety to be applied in clinical settings.

MicroRNA: A new player in response to therapy for colorectal cancer.

Colorectal cancer (CRC) is one of the important malignancies that result in cancer-related deaths worldwide. Multiple lines of evidence have indicated that different responses to therapy in CRC cells led to the failure of the current therapies. Hence, identification of the underlying cellular and molecular pathways involved in the emergence of different responses from CRC cells could contribute to finding and designing new therapeutic platforms to overcome the present limitations. Among the various targets involved in CRC pathogenesis, microRNAs (miRNAs) have key roles in many signaling pathways that are associated with the initiation and progression of CRC. Increasing evidence has confirmed that miRNAs as epigenetic regulators could play critical roles in the response (resistance or sensitivity) to therapy. Cancer stem cells are well-known players in resistance to therapy in CRC. They have been shown to play significant roles via inhibition and activation of many miRNA networks. Hence, miRNAs could be involved in the resistance and sensitivity of therapy in CRC cells via affecting different mechanisms, such as activation of cancer stem cells. Here, we summarized the role of various miRNAs in response to therapy of CRC cells. Moreover, we highlighted the roles of these molecules in the function of cancer stem cells, which are known as important players in the resistance to therapy in CRC.

Leukemia-derived exosomes: Bringing oncogenic signals to blood cells.

Leukemia is a cancer, which is derived from leukocytes and precursors of leukocytes in the bone marrow. A large number of pivotal biological processes are linked to leukemia pathogenesis. More insights into these mechanisms can provide a better developing pharmacological platform for patients with leukemia. Among the different players in leukemia pathogenesis, exosomes have appeared as a new biological vehicle, which can transfer oncogenic signals to blood cells. Exosomes are nano-carriers, which enable transferring numerous cargos such as DNA fragments, RNAs, messenger RNAs, microRNAs, long noncoding RNA, and proteins. Targeting the contents of exosomes leads to the alteration of host cell behavior. Increasing evidence has indicated that leukemia-derived exosomes could be utilized as prognostic, diagnostic, and therapeutic biomarkers for individuals suffering from leukemia. In this regard, the importance of exosomes in terms of initiation and progression of leukemia was underlined in this study.

MicroRNAs and response to therapy in leukemia.

A variety of epigenetic factors involved in leukemia pathogenesis. Among various epigenetic factors, microRNAs (miRNAs) have emerged as important players, which affect a sequence of cellular and molecular signaling pathways. Leukemia is known as progressive cancer, which is related to many health problems in the world. It has been shown that the destruction of the blood-forming organs could lead to abnormal effects on the proliferation and development of leukocytes and their precursors. Despite many attempts for approved effective and powerful therapies for patients with leukemia, finding and developing new therapeutic approaches are required. One of the important aspects of leukemia therapy, identification of underlying cellular and molecular mechanisms involved in the pathogenesis of leukemia. Several miRNAs (ie, miR-103, miR-101, mit-7, let-7i, miR-424, miR-27a, and miR-29c) and play major roles in response to therapy in patients with leukemia. miRNAs exert their effects by targeting a variety of targets, which are associated with response to therapy in patients with leukemia. It seems that more understanding about the roles of miRNAs in response to therapy in patients with leukemia could contribute to better treatment of patients with leukemia. Here, for the first time, we summarized various miRNAs, which are involved in response to therapy in the treatment patients with leukemia.

Vaccines for colorectal cancer: an update.

Colorectal cancer (CRC) is known as the third most common and fourth leading cancer associated death worldwide. The occurrence of metastasis has remained as a critical challenge in CRC, so that distant metastasis (mostly to the liver) has been manifested in about 20%-25% of patients. Several screening approaches have introduced for detecting CRC in different stages particularly in early stages. The standard treatments for CRC are surgery, chemotherapy and radiotherapy, in alone or combination. Immunotherapy is a set of novel approaches with the aim of remodeling the immune system battle with metastatic cancer cells, such as immunomodulatory monoclonal antibodies (immune checkpoint inhibitors), adoptive cell transfer (ACT) and cancer vaccine. Cancer vaccines are designed to trigger the intense response of immune system to tumor-specific antigens. In two last decades, introduction of new cancer vaccines and designing several clinical trials with vaccine therapy, have been taken into consideration in colon cancer patients. This review will describe the treatment approaches with the special attention to vaccines applied to treat colorectal cancer.

A multiscale finite element model of left ventricular mechanics incorporating baroreflex regulation.

Cardiovascular function is regulated by a short-term hemodynamic baroreflex loop, which tries to maintain arterial pressure at a normal level. In this study, we present a new multiscale model of the cardiovascular system named MyoFE. This framework integrates a mechanistic model of contraction at the myosin level into a finite-element-based model of the left ventricle pumping blood through the systemic circulation. The model is coupled with a closed-loop feedback control of arterial pressure inspired by a baroreflex algorithm previously published by our team. The reflex loop mimics the afferent neuron pathway via a normalized signal derived from arterial pressure. The efferent pathway is represented by a kinetic model that simulates the net result of neural processing in the medulla and cell-level responses to autonomic drive. The baroreflex control algorithm modulates parameters such as heart rate and vascular tone of vessels in the lumped-parameter model of systemic circulation. In addition, it spatially modulates intracellular Ca2+ dynamics and molecular-level function of both the thick and the thin myofilaments in the left ventricle. Our study demonstrates that the baroreflex algorithm can maintain arterial pressure in the presence of perturbations such as acute cases of altered aortic resistance, mitral regurgitation, and myocardial infarction. The capabilities of this new multiscale model will be utilized in future research related to computational investigations of growth and remodeling.

Multiscale Finite Element Modeling of Left Ventricular Growth in Simulations of Valve Disease.

Multiscale models of the cardiovascular system are emerging as effective tools for investigating the mechanisms that drive ventricular growth and remodeling. These models can predict how molecular-level mechanisms impact organ-level structure and function and could provide new insights that help improve patient care. MyoFE is a multiscale computer framework that bridges molecular and organ-level mechanisms in a finite element model of the left ventricle that is coupled with the systemic circulation. In this study, we extend MyoFE to include a growth algorithm, based on volumetric growth theory, to simulate concentric growth (wall thickening/thinning) and eccentric growth (chamber dilation/constriction) in response to valvular diseases. Specifically in our model, concentric growth is controlled by time-averaged total stress along the fiber direction over a cardiac cycle while eccentric growth responds to time-averaged intracellular myofiber passive stress over a cardiac cycle. The new framework correctly predicted different forms of growth in response to two types of valvular diseases, namely aortic stenosis and mitral regurgitation. Furthermore, the model predicted that LV size and function are nearly restored (reversal of growth) when the disease-mimicking perturbation was removed in the simulations for each valvular disorder. In conclusion, the simulations suggest that time-averaged total stress along the fiber direction and time-averaged intracellular myofiber passive stress can be used to drive concentric and eccentric growth in simulations of valve disease.

Multiscale fiber remodeling in the infarcted left ventricle using a stress-based reorientation law.

The organization of myofibers and extra cellular matrix within the myocardium plays a significant role in defining cardiac function. When pathological events occur, such as myocardial infarction (MI), this organization can become disrupted, leading to degraded pumping performance. The current study proposes a multiscale finite element (FE) framework to determine realistic fiber distributions in the left ventricle (LV). This is achieved by implementing a stress-based fiber reorientation law, which seeks to align the fibers with local traction vectors, such that contractile force and load bearing capabilities are maximized. By utilizing the total stress (passive and active), both myofibers and collagen fibers are reoriented. Simulations are conducted to predict the baseline fiber configuration in a normal LV as well as the adverse fiber reorientation that occurs due to different size MIs. The baseline model successfully captures the transmural variation of helical fiber angles within the LV wall, as well as the transverse fiber angle variation from base to apex. In the models of MI, the patterns of fiber reorientation in the infarct, border zone, and remote regions closely align with previous experimental findings, with a significant increase in fibers oriented in a left-handed helical configuration and increased dispersion in the infarct region. Furthermore, the severity of fiber reorientation and impairment of pumping performance both showed a correlation with the size of the infarct. The proposed multiscale modeling framework allows for the effective prediction of adverse remodeling and offers the potential for assessing the effectiveness of therapeutic interventions in the future. STATEMENT OF SIGNIFICANCE: The organization of muscle and collagen fibers within the heart plays a significant role in defining cardiac function. This organization can become disrupted after a heart attack, leading to degraded pumping performance. In the current study, we implemented a stress-based fiber reorientation law into a computer model of the heart, which seeks to realign the fibers such that contractile force and load bearing capabilities are maximized. The primary goal was to evaluate the effects of different sized heart attacks. We observed substantial fiber remodeling in the heart, which matched experimental observations. The proposed computational framework allows for the effective prediction of adverse remodeling and offers the potential for assessing the effectiveness of therapeutic interventions in the future.

Super-Tough PLA-Based Blends with Excellent Stiffness and Greatly Improved Thermal Resistance via Interphase Engineering.

Super-tough poly(lactic acid)/polycarbonate (PLA/PC) (50/50) blends with an excellent balance of stiffness, toughness, and thermal stability were systematically designed and characterized. Poly(methyl methacrylate) (PMMA) was utilized as a novel, highly effective nonreactive interphase to promote PLA-PC phase compatibility. Partial miscibility of PMMA with both PLA and PC produced strong molecular entanglements across the PLA-PC phase boundary followed by an excellent phase adhesion. This was predicted from interfacial energy measurements and supported by dynamic mechanical thermal analysis, morphological observations, and mechanical tests. Ternary PLA/PC/PMMA blends exhibited an exceptional set of stiffness, tensile and flexural strength, tensile and flexural ductility, and thermal stability together with improved impact strength compared with neat PLA and uncompatibilized PLA/PC blends. Addition of nonreactive polybutadiene-g-styrene-co-acrylonitrile (PB-g-SAN) impact modifier to the compatibilized blend resulted in further dramatic improvements in the dispersion state of PC and PMMA phase domains followed by the development of an interconnected structure of PC, PMMA, and PB-g-SAN domains in the PLA matrix. Such a network-like morphology, with rubbery particles percolated at the interface between the dispersed structures and surrounding PLA matrix, produced a tremendous increase in impact resistance (≈700 J/m) and tensile ductility (≈200% strain) while maintaining excellent stiffness (≥2.1 GPa). The combined effects of interfacial localization of impact modifier particles, network-like morphology (extended over the entire volume of the blend), and strong phase interactions between the components (due to mutual miscibility) are described to be responsible for super-tough behavior. The role of PMMA as an efficient interphase adhesion promoter in the toughened quaternary blends is also clarified. Impact fractography revealed multiple void formations, plastic growth of microvoids, and the formation of void-fibrillar structures around as well as inside the dispersed structures as the main micromechanical deformation processes responsible for massive shear yielding and plastic deformation of blends. Blends designed in this work offer remarkable improvements in tensile and flexural ductility, impact resistance, and heat deflection temperature compared with neat PLA resin. The overall characteristics of these blend systems are comparable and/or superior to those of several commercial thermoplastic resins.

A systematic literature review on the use of big data analytics in humanitarian and disaster operations.

At the start of this review, 168 million individuals required humanitarian assistance, at the conclusion of the research, the number had risen to 235 million. Humanitarian aid is critical not just for dealing with a pandemic that occurs once every century, but more for assisting amid civil conflicts, surging natural disasters, as well as other kinds of emergencies. Technology's dependability to support humanitarian and disaster operations has never been more pertinent and significant than it is right now. The ever-increasing volume of data, as well as innovations in the field of data analytics, present an incentive for the humanitarian sector. Given that the interaction between big data and humanitarian and disaster operations is crucial in the coming days, this systematic literature review offers a comprehensive overview of big data analytics in a humanitarian and disaster setting. In addition to presenting the descriptive aspects of the literature reviewed, the results explain review of existent reviews, the current state of research by disaster categories, disaster phases, disaster locations, and the big data sources used. A framework is also created to understand why researchers employ various big data sources in different crisis situations. The study, in particular, uncovered a considerable research disparity in the disaster group, disaster phase, and disaster regions, emphasising how the focus is on reactionary interventions rather than preventative approaches. These measures will merely compound the crisis, and so is the reality in many COVID-19-affected countries. Implications for practice and policy-making are also discussed.

A multiscale model of the cardiovascular system that regulates arterial pressure via closed loop baroreflex control of chronotropism, cell-level contractility, and vascular tone.

Multiscale models of the cardiovascular system can provide new insights into physiological and pathological processes. PyMyoVent is a computer model that bridges from molecular- to organ-level function and which simulates a left ventricle pumping blood through the systemic circulation. Initial work with PyMyoVent focused on the end-systolic pressure volume relationship and ranked potential therapeutic strategies by their impact on contractility. This manuscript extends the PyMyoVent framework by adding closed-loop feedback control of arterial pressure. The control algorithm mimics important features of the physiological baroreflex and was developed as part of a long-term program that focuses on growth and biological remodeling. Inspired by the underlying biology, the reflex algorithm uses an afferent signal derived from arterial pressure to drive a kinetic model that mimics the net result of neural processing in the medulla and cell-level responses to autonomic drive. The kinetic model outputs control signals that are constrained between limits that represent maximum parasympathetic and maximum sympathetic drive and which modulate heart rate, intracellular Ca2+ dynamics, the molecular-level function of both the thick and the thin myofilaments, and vascular tone. Simulations show that the algorithm can regulate mean arterial pressure at user-defined setpoints as well as maintaining arterial pressure when challenged by changes in blood volume and/or valve resistance. The reflex also regulates arterial pressure when cell-level contractility is modulated to mimic the idealized impact of myotropes. These capabilities will be important for future work that uses computer modeling to investigate clinical conditions and treatments.

The Impact of One Week of Pre-Stenting on Porcine Ureteral Luminal Circumference.

Objectives: Larger ureteral access sheaths (UASs) have the potential to improve ureteroscopic stone removal outcomes but are often avoided by surgeons because of concerns of ureteral injury. Using our novel UAS force sensor and previously defined force thresholds for ureteral injury, we sought to evaluate the impact of 1 week of stenting on the maximum safe dilation of ureteral luminal circumference. Methods: Twelve juvenile female Yorkshire pigs (24 ureters) were evaluated. The inner (i.e., luminal) circumference of each ureter was determined using Cook urethral dilators ranging from 8F to 24F in 2F increments, 37 cm in length. Each dilator was sequentially passed while applying the UAS force sensor to measure insertion force before and after 1 week of stent placement. Each ureter was randomized to receive either a 4.7F or 7.0F stent (20 cm). Maximum ureteral luminal circumference was defined as effective passage of the dilator to the ureteropelvic junction with ≤6 newtons (N) of force (the force threshold previously defined by porcine and clinical studies to avoid ureteral damage). After passage of the largest dilator at 6 N, flexible ureteroscopy was performed and a post-ureteroscopic lesion scale (PULS) was recorded. Results: After 1 week of stent placement, the median ureteral luminal circumference increased to 15F representing a mean increase of 3.8F ± 2.8F (p < 0.001). Twenty-one (88%) of the pre-stented ureters had an increase in luminal circumference, with 12 ureters (50%) dilated to ≥16F (p = 0.032), 6 ureters (25%) dilated to ≥18F, and in 2 cases a maximum size of 24F was recorded. The PULS grade was ≤2 in all cases, indicating no high-grade ureteral injuries. Laterality and stent size did not impact ureteral luminal circumference after pre-stenting (p = 0.232 and p = 0.337, respectively). Conclusions: One week of ureteral stenting resulted in nearly a 4F increase in the luminal circumference of porcine ureters.

Reproducibility of Systolic Strain in Mice Using Cardiac Magnetic Resonance Feature Tracking of Black-Blood Cine Images.

PURPOSE: Mouse models are widely utilized to enhance our understanding of cardiac disease. The goal of this study is to investigate the reproducibility of strain parameters that were measured in mice using cardiac magnetic resonance (CMR) feature-tracking (CMR42, Canada). METHODS: We retrospectively analyzed black-blood CMR datasets from thirteen C57BL/6 B6.SJL-CD45.1 mice (N = 10 female, N = 3 male) that were imaged previously. The circumferential, longitudinal, and radial (Ecc, Ell, and Err, respectively) parameters of strain were measured in the mid-ventricular region of the left ventricle. Intraobserver and interobserver reproducibility were assessed for both the end-systolic (ES) and peak strain. RESULTS: The ES strain had larger intraclass correlation coefficient (ICC) values when compared to peak strain, for both the intraobserver and interobserver reproducibility studies. Specifically, the intraobserver study showed excellent reproducibility for all three ES strain parameters, namely, Ecc (ICC 0.95, 95% CI 0.83-0.98), Ell (ICC 0.90, 95% CI 0.59-0.97), and Err (ICC 0.92, 95% CI 0.73-0.97). This was also the case for the interobserver study, namely, Ecc (ICC 0.92, 95% CI 0.60-0.98), Ell (ICC 0.76, 95% CI 0.33-0.93), and Err (ICC 0.93, 95% CI 0.68-0.98). Additionally, the coefficient of variation values were all < 10%. CONCLUSION: The results of this preliminary study showed excellent reproducibility for all ES strain parameters, with good to excellent reproducibility for the peak strain parameters. Moreover, all ES strain parameters had larger ICC values than the peak strain. In general, these results imply that feature-tracking with CMR42 software and black-blood cine images can be reliably used to assess strain patterns in mice.

Multiscale simulations of left ventricular growth and remodeling.

Cardiomyocytes can adapt their size, shape, and orientation in response to altered biomechanical or biochemical stimuli. The process by which the heart undergoes structural changes-affecting both geometry and material properties-in response to altered ventricular loading, altered hormonal levels, or mutant sarcomeric proteins is broadly known as cardiac growth and remodeling (G&R). Although it is likely that cardiac G&R initially occurs as an adaptive response of the heart to the underlying stimuli, prolonged pathological changes can lead to increased risk of atrial fibrillation, heart failure, and sudden death. During the past few decades, computational models have been extensively used to investigate the mechanisms of cardiac G&R, as a complement to experimental measurements. These models have provided an opportunity to quantitatively study the relationships between the underlying stimuli (primarily mechanical) and the adverse outcomes of cardiac G&R, i.e., alterations in ventricular size and function. State-of-the-art computational models have shown promise in predicting the progression of cardiac G&R. However, there are still limitations that need to be addressed in future works to advance the field. In this review, we first outline the current state of computational models of cardiac growth and myofiber remodeling. Then, we discuss the potential limitations of current models of cardiac G&R that need to be addressed before they can be utilized in clinical care. Finally, we briefly discuss the next feasible steps and future directions that could advance the field of cardiac G&R.

Cancer stem cells as therapeutic targets of pancreatic cancer.

The discovery of stem cells and their potential abilities in self-renewal and differentiation has opened a new horizon in medicine. Scientists have found a small population of stem cells in some types of cancers with the same functions as normal stem cells. There are two models for tumor progression: clonal (stochastic) and cancer stem cell (CSCs) models. According to the first model, all transformed cells in the tumor have carcinogenic potential and are able to proliferate and produce the same cells. The latter model, which has received more attention recently, considers the role of CSCs in drug resistance and tumor metastasis. Following the model, researchers have found that targeting CSCs may be a promising way in cancer therapy. This review describes CSC characteristics in general, while also focusing on CSC properties in the context of pancreatic cancer.

Stachys lavandulifolia Vahl. and its Relation With Marmazad Activities in Traditional Manuscripts.

CONTEXT: In modern phytotherapy, Stachys lavandulifolia Vahl., a type of Stachys also known as Mountain Tea (Chay-e-Kouhi) has been widely studied based on its botanical and therapeutic characteristics over the recent decades. EVIDENCE ACQUISITION: The present study investigated morphology, botanical characteristics, and some therapeutic activities of this plant and compares them with those of Marmazad, as the traditional equivalent of Stachys in traditional iranian medicine (TIM), to evaluate the similarities between Stachys and Marmazad. RESULTS: In this study by exploring morphology, botanical properties and therapeutic activities of Stachys from modern botany and Marmazad in TIM, comparing them and considering similarities between those botanical properties and some of therapeutic activities this outcome was drawn that what had been known as Marmazad in TIM nowadays is equal to Stachys or Chay-e-Kouhi in modern botany. CONCLUSIONS: The achieved findings from this comparison between botanical characteristics and therapeutic activities of Stachys based on modern researches and those of Marmazad by referring to traditional manuscripts revealed significant similarities between them. Also, there were some applications mentioned for Marmazad in TIM which could help new researchers in modern phytotherapy to deal with those dimensions of this herb which are not worked out yet.

Causes and risk factors of urinary incontinence: Avicenna's point of view vs. contemporary findings.

PURPOSE: To extract the causes and risk factors of urinary incontinence from an old medical text by Avicenna entitled "Canon of Medicine" and comparing it with contemporary studies. MATERIALS AND METHODS: In this study, etiology and risk factors of urinary incontinence were extracted from Avicenna's "Canon of Medicine". Commentaries written on this book and other old reliable medical texts about bladder and its diseases were also studied. Then the achieved information was compared with contemporary findings of published articles. RESULTS: Urinary incontinence results from bladder dysfunction in reservoir phase. Bladder's involuntary muscles and voluntary external sphincter are two main components which are involved in this process. Urinary incontinence can exist without obvious structural and neuronal etiologies. According to Avicenna, distemperment of muscular tissue of bladder and external sphincter is the cause for urinary incontinence in such cases. Distemperment is the result of bothering qualities in tissue, i.e.: "wet" and "cold". They are the two bothering qualities which are caused by extracorporeal and intracorporeal factors. Interestingly, the positive associations of some of these factors with urinary incontinence have been shown in recent researches. CONCLUSION: "Cold" and "wet" distemperment of bladder and external sphincter can be independent etiologies of urinary incontinence which should be investigated.