Impact of diabetes mellitus on mortality in pulmonary hypertension: A systematic review and meta-analysis.

Background: Pulmonary hypertension (PH) is a progressive disease characterized by endothelial dysfunction and vascular remodeling and is a leading cause of mortality worldwide. Although it is independently associated with multiple comorbidities, the impact of diabetes mellitus (DM) on mortality in patients with PH remains uncertain. To address this issue, we conducted a systematic review and meta-analysis to investigate the effect of DM on survival in patients with pulmonary hypertension.

A First Insight into the Developability of an Immunoglobulin G3: A Combined Computational and Experimental Approach.

Immunoglobulin G 3 (IgG3) monoclonal antibodies (mAbs) are high-value scaffolds for developing novel therapies. Despite their wide-ranging therapeutic potential, IgG3 physicochemical properties and developability characteristics remain largely under-characterized. Protein-protein interactions elevate solution viscosity in high-concentration formulations, impacting physicochemical stability, manufacturability, and the injectability of mAbs.

A framework for the biophysical screening of antibody mutations targeting solvent-accessible hydrophobic and electrostatic patches for enhanced viscosity profiles.

The formulation of high-concentration monoclonal antibody (mAb) solutions in low dose volumes for autoinjector devices poses challenges in manufacturability and patient administration due to elevated solution viscosity. Often many therapeutically potent mAbs are discovered, but their commercial development is stalled by unfavourable developability challenges. In this work, we present a systematic experimental framework for the computational screening of molecular descriptors to guide the design of 24 mutants with modified viscosity profiles accompanied by experimental evaluation.

Lyotropic liquid crystals for parenteral drug delivery.

The necessity for long-term treatments of chronic diseases has encouraged the development of novel long-acting parenteral formulations intending to improve drug pharmacokinetics and therapeutic efficacy. Lately, one of the novel approaches has been developed based on lipid-based liquid crystals. The lyotropic liquid crystal (LLC) systems consist of amphiphilic molecules and are formed in presence of solvents with the most common types being cubic, hexagonal and lamellar mesophases.

Microfluidics Formulated Liposomes of Hypoxia Activated Prodrug for Treatment of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) presents as an unmet clinical challenge for drug delivery due to its unique hypoxic biology. Vinblastine-N-Oxide (CPD100) is a hypoxia-activated prodrug (HAP) that selectively converts to its parent compound, vinblastine, a potent cytotoxic agent, under oxygen gradient. The study evaluates the efficacy of microfluidics formulated liposomal CPD100 (CPD100Li) in PDAC.

A clinically relevant formulation for direct administration of nerve specific fluorophores to mitigate iatrogenic nerve injury.

Iatrogenic nerve injury significantly affects surgical outcomes. Although intraoperative neuromonitoring is utilized, nerve identification remains challenging and the success of nerve sparing is strongly correlated with surgeon experience levels. Fluorescence guided surgery (FGS) offers a potential solution for improved nerve sparing by providing direct visualization of nerve tissue intraoperatively.

Early Experience of High-dose Intravenous in Critically Ill Patients of COVID-19.

Background: Immune dysregulation is one of the main reasons for mortality and morbidity in coronavirus disease 2019 (COVID-19). Mycobacterium w (Mw) is recently approved for gram-negative sepsis. Moreover, it is also found effective in COVID-19 patients in previous studies.

Clinically translatable formulation strategies for systemic administration of nerve-specific probes.

Nerves are extremely difficult to identify and are often accidently damaged during surgery, leaving patients with lasting pain and numbness. Herein, a novel near-infrared (NIR) nerve-specific fluorophore, LGW01-08, was utilized for enhanced nerve identification using fluorescence guided surgery (FGS), formulated using clinical translatable strategies. Formulated LGW01-08 was examined for toxicology, pharmacokinetics (PK), and pharmacodynamics (PD) parameters in preparation for future clinical translation.

Metabolic convergence on lipogenesis in RAS, BCR-ABL, and MYC-driven lymphoid malignancies.

Background: Metabolic reprogramming is a central feature in many cancer subtypes and a hallmark of cancer. Many therapeutic strategies attempt to exploit this feature, often having unintended side effects on normal metabolic programs and limited efficacy due to integrative nature of metabolic substrate sourcing. Although the initiating oncogenic lesion may vary, tumor cells in lymphoid malignancies often share similar environments and potentially similar metabolic profiles.

Thermoresponsive liquid crystalline formulation of Exemestane: Design and structural characterization.

Exemestane (EXE), a drug used for the treatment of breast cancer, has limited aqueous solubility of 0.08 mg/mL and log P∼ 4.22.

Prematurity and postnatal alterations in intermittent hypoxaemia.

Intermittent hypoxaemia (IH) events are well described in extremely preterm infants, but the occurrence of IH patterns in more mature preterm infants remains unclear. The objective of this study was to characterise the effect of gestational age on early postnatal patterns of IH in extremely (<28 weeks), very (28-<32 weeks) and moderately (32-<34 weeks) preterm infants. As expected, extremely preterm infants had a significantly higher frequency of IH events of longer durations and greater time with hypoxaemia versus very and moderately preterm infants.

Visual Rehabilitation With Contact Lenses Following Open Globe Trauma.

Objectives: To describe visual outcomes with various contact lens modalities in patients with a history of ocular trauma who underwent surgical open globe repair.

Methods: Records of all patients with a history of open globe injury and repair at a tertiary care hospital between January 1, 2010, and December 31, 2016, were reviewed. Demographics, type of injury, and visual acuity were assessed before and after contact lens evaluation.

Hypoxia: Friend or Foe for drug delivery in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal solid tumors with an overall five-year survival rate of that has only just reached 10%. The tumor microenvironment of PDAC is characterized by desmoplasia, which consist of dense stroma of fibroblasts and inflammatory cells, resulting in a hypoxic environment due to limited oxygen diffusion through the tumor. Hypoxia contributes to the aggressive tumor biology by promoting tumor progression, malignancy, and promoting resistance to conventional and targeted therapeutic agents.

The Relationship between Oxidative Stress, Intermittent Hypoxemia, and Hospital Duration in Moderate Preterm Infants.

Introduction: Lipid peroxidation products are present following oxidation of polyunsaturated fatty acids in the eye, brain, and various cell membranes. Elevated levels of lipid peroxidation products and increased intermittent hypoxemia (IH) events have been associated with adverse outcomes in extremely preterm infants. The moderate preterm newborn has a still-developing oxidant defense system and immature respiratory control, but little is known about lipid peroxidation levels and IH in this larger and more common preterm population.

Select Stabilization of a Tumor-Suppressive PP2A Heterotrimer.

In cancer, suppression of protein phosphatases, such as protein phosphatase 2A (PP2A), that normally counteract kinases, contributes to aberrant signaling. Leonard et al. recently demonstrated that a novel small-molecule activator of PP2A, DT-061, selectively stabilizes a specific PP2A holoenzyme responsible for dephosphorylating critical oncogenic targets, including MYC.

Development of probiotic yogurt: effect of strain combination on nutritional, rheological, organoleptic and probiotic properties.

Seven combinations of yogurt; C [yogurt starter culture ()], T, [ +  ()], T [ +  ()], T [ +  ()], T [ +  ()], T [ +  + ] and T [ +  + ] were developed. Nutritional [proximate and minerals], rheological [total soluble solids (TSS), pH, titratable acidity (TA), water holding capacity, synersis, viscosity] organoleptic and probiotic properties [viability, acid tolerance, bile salt tolerance] were assessed with standard methods. Nutritional composition differed significantly among samples except for the iron and zinc ( < 0.

Chemosensitization and mitigation of Adriamycin-induced cardiotoxicity using combinational polymeric micelles for co-delivery of quercetin/resveratrol and resveratrol/curcumin in ovarian cancer.

This work looks to improve the efficacy of Adriamycin (ADR) while mitigating its cardiotoxicity using combinations of micellar resveratrol (R): quercetin (Q) (mRQ) or R: curcumin (C) (mRC) in healthy mice and ovarian cancer xenograft models. Ovarian cancer cells, ES2-Luc, or A2780ADR are inoculated in mice (n =4/group) and sorted into eight cohorts. Mice are treated weekly for 4 weeks with ADR, ADR+mRQ, ADR+mRC, or controls (saline, empty micelles, ADR+EM, mRQ, or mRC).

Spectral Doppler Ultrasound Can Help Diagnose Children With Hepatic Sinusoidal Obstructive Syndrome After Hematopoietic Stem Cell Transplantation.

Background: Hepatic sinusoidal obstruction syndrome (SOS) is a potentially fatal complication after hematopoietic stem cell transplantation (HSCT). Current clinical guidelines state that spectral Doppler changes occur late in the disease, and imaging is only useful for confirming SOS diagnosis.

Objective: Our primary objective was to examine abdominal ultrasound variables as predictors of development of SOS in pediatric HSCT patients.

Liposomes produced by microfluidics and extrusion: A comparison for scale-up purposes.

Successful liposomal formulations in the clinic are severely limited due to poor translational capability of the traditional bench techniques to clinical production settings. The gold standard for liposome bench manufacturing is a multi-step and parameter dependent extrusion method. Moreover, these parameters need re-optimization for clinical production.

Adrenic acid non-enzymatic peroxidation products in biofluids of moderate preterm infants.

Oxidative stress plays an essential role in processes of signaling and damage to biomolecules during early perinatal life. Isoprostanoids and isofuranoids from the free radical-catalyzed peroxidation of polyunsaturated fatty acids (PUFAs) are widely recognized as reliable biomarkers of oxidative stress. However, their quantification is not straightforward due to high structural similarity of the compounds formed.

Liposomal formulation of hypoxia activated prodrug for the treatment of ovarian cancer.

In this work, a new sphingomyelin-cholesterol liposomal formulation (CPD100Li) for the delivery of a hypoxia activated prodrug of vinblastine, mon-N-oxide (CPD100), is developed. The optimized liposomal formulation uses an ionophore (A23187) mediated pH-gradient method. Optimized CPD100Li is characterized for size, drug loading, and stability.