Effect of Hypoglycemia on QT Interval in Individuals with and without Type 2 Diabetes: A Randomized Crossover Trial.

Background: Our goal was to determine in healthy individuals and individuals with type 2 diabetes the impact of repeated episodes of hypoglycemia on the corrected QT (QTc) interval and the time course for QTc recovery. Further, since hypoglycemia increases aldosterone and patients with primary aldosteronism have prolonged QTc, we also determined whether mineralocorticoid receptor blockade prevents hypoglycemia-induced QTc alterations.

Methods: Twenty-seven healthy participants completed a double-blinded crossover trial contrasting 3 experimental conditions: 1) euglycemia, 2) hypoglycemia, and 3) hypoglycemia with mineralocorticoid receptor blockade pretreatment.

PgtE protease enables virulent to evade C3-mediated serum and neutrophil killing.

Non-typhoidal serovars, such as serovar Typhimurium (STm), are a leading cause of inflammatory diarrhea in otherwise healthy individuals. Among children, the elderly, and immunocompromised individuals, STm can spread to systemic sites and cause potentially lethal bacteremia. Phagocytic cells and the immune complement system are pivotal to preventing the dissemination of STm.

Drug resistant pancreatic cancer cells exhibit altered biophysical interactions with stromal fibroblasts in imaging studies of 3D co-culture models.

Interactions between tumor and stromal cells are well known to play prominent roles in progression of pancreatic ductal adenocarcinoma (PDAC). As knowledge of stromal crosstalk in PDAC has evolved, it has become clear that cancer associated fibroblasts can play both tumor promoting and tumor suppressive roles through a combination of paracrine crosstalk and juxtacrine interactions involving direct physical contact. Another major contributor to dismal survival statistics for PDAC is development of resistance to chemotherapy drugs, though less is known about how the acquisition of chemoresistance impacts upon tumor-stromal crosstalk.

Drug resistant pancreatic cancer cells exhibit altered biophysical interactions with stromal fibroblasts in imaging studies of 3D co-culture models.

Interactions between tumor and stromal cells are well known to play a prominent roles in progression of pancreatic ductal adenocarcinoma (PDAC). As knowledge of stromal crosstalk in PDAC has evolved, it has become clear that cancer associated fibroblasts can play both tumor promoting and tumor suppressive roles through a combination of paracrine crosstalk and juxtacrine interactions involving direct physical contact. Another major contributor to dismal survival statistics for PDAC is development of resistance to chemotherapy drugs.

Influence of Different Photobiomodulation Parameters on Multi-Potent Adipose Tissue Mesenchymal Cells .

Investigating the effect of different parameters of photobiomodulation (PBM) with low-power laser on multi-potent mesenchymal stem cells (MSCs) derived from adipose tissue in terms of proliferation and cell death. MSCs were submitted to PBM applications with combinations of the following physical parameters: control group (no intervention), wavelengths of 660 and 830 nm; energy of 0.5, 2, and 4 J; and power of 40 and 100 mW.

Effect of hypoglycemia on baroreflex sensitivity in individuals with type 2 diabetes: implications for autonomic control of cardiovascular function in diabetes.

Purpose: Hypoglycemia is associated with increased mortality, though the mechanisms underlying this association are not established. Hypoglycemia impairs the counterregulatory hormonal and autonomic responses to subsequent hypoglycemia. It is unknown whether hypoglycemia elicits a generalized impairment in autonomic control of cardiovascular function in individuals with type 2 diabetes.

Clinical assessment of a low-cost, hand-held, smartphone-attached intraoral imaging probe for 5-aminolevulinic acid photodynamic therapy monitoring and guidance.

Significance: India has one of the highest rates of oral squamous cell carcinoma (OSCC) in the world, with an incidence of 15 per 100,000 and more than 70,000 deaths per year. The problem is exacerbated by a lack of medical infrastructure and routine screening, especially in rural areas. New technologies for oral cancer detection and timely treatment at the point of care are urgently needed.

Discovery of a glutathione utilization pathway in Francisella that shows functional divergence between environmental and pathogenic species.

Glutathione (GSH) is an abundant metabolite within eukaryotic cells that can act as a signal, a nutrient source, or serve in a redox capacity for intracellular bacterial pathogens. For Francisella, GSH is thought to be a critical in vivo source of cysteine; however, the cellular pathways permitting GSH utilization by Francisella differ between strains and have remained poorly understood. Using genetic screening, we discovered a unique pathway for GSH utilization in Francisella.

Blackfoot Words: a database of Blackfoot lexical forms.

This paper describes the structure and creation of Blackfoot Words, a new relational database of lexical forms (inflected words, stems, and morphemes) in Blackfoot (Algonquian; ISO 639-3: bla). To date, we have digitized 63,493 individual lexical forms from 30 sources, representing all four major dialects, and spanning the years 1743-2017. Version 1.

The Brucella abortus Type IV Effector BspA Inhibits MARCH6-Dependent ERAD To Promote Intracellular Growth.

Brucella abortus, the intracellular causative agent of brucellosis, relies on type IV secretion system (T4SS) effector-mediated modulation of host cell functions to establish a replicative niche, the Brucella-containing vacuole (BCV). Brucella exploits the host's endocytic, secretory, and autophagic pathways to modulate the nature and function of its vacuole from an endocytic BCV (eBCV) to an endoplasmic reticulum (ER)-derived replicative BCV (rBCV) to an autophagic egress BCV (aBCV). A role for the host ER-associated degradation pathway (ERAD) in the B.

On the need for standardized reporting of photophysical parameters of in vitro photodynamic therapy studies.

In vitro dose escalation experiments are one of the first gatekeepers in therapeutic evaluation and development. This also holds for evaluating novel photosensitizers (PS) and Photodynamic Therapy (PDT) co-therapies as needed to provide dose response guidelines before engaging in further pre-clinical studies. The dose needed to achieve 50% cell kill (LD) is a standard metric to report the potency of a therapeutic agents that is widely accepted for single-drug therapies.

Photodynamic Stromal Depletion Enhances Therapeutic Nanoparticle Delivery in 3D Pancreatic Ductal Adenocarcinoma Tumor Models.

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of human malignancies. PDAC is characterized by dense fibrous stroma which obstructs drug delivery and plays complex tumor-promoting roles. Photodynamic therapy (PDT) is a light-based modality which has been demonstrated to be clinically feasible and effective for tumors of the pancreas.

Clinical evaluation of a mobile, low-cost system for fluorescence guided photodynamic therapy of early oral cancer in India.

Background: Morbidity and mortality due to oral cancer in India are exacerbated by a lack of access to effective treatments amongst medically underserved populations. We developed a user-friendly low-cost, portable fibre-coupled LED system for photodynamic therapy (PDT) of early oral lesions, using a smartphone fluorescence imaging device for treatment guidance, and 3D printed fibreoptic attachments for ergonomic intraoral light delivery.

Methods: 30 patients with TNM buccal mucosal cancer were recruited from the JN Medical College clinics, Aligarh, and rural screening camps.

Laser light sources for photobiomodulation: The role of power and beam characterization in treatment accuracy and reliability.

Purpose: Daily clinical use of therapeutic light sources can lead to changes in light emission stability with potentially significant consequences for usage in photomedicine treatment. The aim of this study was to evaluate the average and maximum power and to describe the beam diameter of different low-power laser photobiomodulation devices in clinical use in Brazil.

Methods: The power and light-emitting beam diameter of twenty-four therapeutic devices with an average age of 11±5 years, with an average weekly use of fewer than thirty minutes, were measured.

Image-Based Quantification of Gold Nanoparticle Uptake and Localization in 3D Tumor Models to Inform Radiosensitization Schedule.

Gold nanoparticles (GNPs) have shown particular promise as radiosensitizing agents and as complementary drug delivery agents to improve therapeutic index in cancer treatment. Optimal implementation, however, depends critically on the localization of GNPs at the time of irradiation, which, in turn, depends on their size, shape, and chemical functionalization, as well as organism-level pharmacokinetics and interactions with the tumor microenvironment. Here, we use in vitro 3D cultures of A549 lung carcinoma cells, which recapitulate interaction with extracellular matrix (ECM) components, combined with quantitative fluorescence imaging to study how time-dependent localization of ultrasmall GNPs in tumors and ECM impacts the degree of damage enhancement to tumor cells.

Clinical Significance and Regulation of ERK5 Expression and Function in Cancer.

Extracellular signal-regulated kinase 5 (ERK5) is a unique kinase among MAPKs family members, given its large structure characterized by the presence of a unique C-terminal domain. Despite increasing data demonstrating the relevance of the ERK5 pathway in the growth, survival, and differentiation of normal cells, ERK5 has recently attracted the attention of several research groups given its relevance in inflammatory disorders and cancer. Accumulating evidence reported its role in tumor initiation and progression.

A Review of Microbial Mediated Iron Nanoparticles (IONPs) and Its Biomedical Applications.

Nanotechnology is a booming avenue in science and has a multitude of applications in health, agriculture, and industry. It exploits materials' size at nanoscale (1-100 nm) known as nanoparticles (NPs). These nanoscale constituents are made via chemical, physical, and biological methods; however, the biological approach offers multiple benefits over the other counterparts.

Photodynamic Therapy for Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of human cancers. Clinical trials of various chemotherapy, radiotherapy, targeted agents and combination strategies have generally failed to provide meaningful improvement in survival for patients with unresectable disease. Photodynamic therapy (PDT) is a photochemistry-based approach that enables selective cell killing using tumor-localizing agents activated by visible or near-infrared light.

A Brucella effector modulates the Arf6-Rab8a GTPase cascade to promote intravacuolar replication.

Remodeling of host cellular membrane transport pathways is a common pathogenic trait of many intracellular microbes that is essential to their intravacuolar life cycle and proliferation. The bacterium Brucella abortus generates a host endoplasmic reticulum-derived vacuole (rBCV) that supports its intracellular growth, via VirB Type IV secretion system-mediated delivery of effector proteins, whose functions and mode of action are mostly unknown. Here, we show that the effector BspF specifically promotes Brucella replication within rBCVs by interfering with vesicular transport between the trans-Golgi network (TGN) and recycling endocytic compartment.

The effector BspL targets the ER-associated degradation (ERAD) pathway and delays bacterial egress from infected cells.

Perturbation of the endoplasmic reticulum (ER), a central organelle of the cell, can have critical consequences for cellular homeostasis. An elaborate surveillance system known as ER quality control ensures that cells can respond and adapt to stress via the unfolded protein response (UPR) and that only correctly assembled proteins reach their destination. Interestingly, several bacterial pathogens hijack the ER to establish an infection.

Photodestruction of Stromal Fibroblasts Enhances Tumor Response to PDT in 3D Pancreatic Cancer Coculture Models.

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of human cancers. The dismal response of PDAC to virtually all therapeutics is associated, in part, with a characteristically dense fibrotic stroma. This stroma not only acts as a barrier to drug perfusion, but also promotes tumor survival through paracrine crosstalk and biophysical interactions.

Special Section Guest Editorial: Photodynamic Therapy.

Guest Editors introduce the Special Section on Photodynamic Therapy for the Journal of Biomedical Optics, Volume 25, Issue 6.

ACTH Infusion Impairs Baroreflex Sensitivity-Implications for Cardiovascular Hypoglycemia-Associated Autonomic Failure.

Context: Hypoglycemia attenuates cardiovascular homeostatic autonomic control. This attenuation, known as the cardiovascular component of hypoglycemia-associated autonomic failure (HAAF), is characterized most notably by decreased baroreflex sensitivity (BRS) that begins during hypoglycemia and persists until at least the next day, despite return to euglycemia. Understanding the mechanisms underlying this reduction in BRS is important because BRS attenuation is associated with increased morbidity and mortality.