Prostate Cancer Therapy Cardiotoxicity Map (PROXMAP) for Advanced Disease States: A Systematic Review and Network Meta-analysis with Bayesian Modeling of Treatment Histories.

Background And Objective: Recommendations of first-line therapies for metastatic hormone-sensitive (mHSPC), nonmetastatic castrate-resistant (M0CRPC), and metastatic castrate-resistant (mCRPC) prostate cancer do not account for cardiotoxicity due to a lack of clear prior evidence. This manuscript assesses cardiotoxicity of these therapies.

Methods: We searched Ovid Medline, Elsevier Embase, and the Cochrane Library for randomized clinical trials (RCTs) from database inception to January 14, 2024.

Comparative Evaluation of Sinus Complication and Survival Rates of Quad Zygoma versus Bizygoma in Combination with two Regular Implants in Atrophic Maxilla: A Systematic Review and Meta-Analysis.

Aim: To systematically review existing scientific literature to determine, compare and evaluate the sinus complication and survival rates of quad zygoma against two zygomatic implants with combination of two regular implants in atrophic maxilla in adults.

Methods: Review was performed in accordance with preferred reporting items for systematic reviews and meta-analysis guidelines and registered in PROSPERO-CRD42023392721 Electronic databases like PubMed, Google scholar and EBSCO host were searched from 2000 to December 2022 for studies reporting treatment of Atrophic maxilla with either quad zygoma or two zygomatic implants in combination with two regular implants. Quality assessment was evaluated using Cochrane risk of bias-2 tool for randomized controlled trials (RCT).

Lemierre's Like Syndrome: Retropharyngeal Abscess With Internal Jugular and Cerebral Venous Thromboses and Septic Embolization Leading to Pulmonary Embolism and Cerebral Abscesses Complicated by Papilledema and Residual Sixth Cranial Nerve Palsy.

A male child with a history of sinusitis presented to the emergency medicine department with a high fever, neck swelling, headache, vomiting, and double vision. He was diagnosed with retropharyngeal abscess (RPA) with bilateral internal jugular vein (IJV) and cerebral venous thromboses. The child was treated promptly and transferred to a specialty center, where the abscess was drained.

Pre-adjusted Three-Dimensional Plate Employing Printing versus Conventional Plate in the Management of Mandibular Fractures - A Comparative Study.

Introduction: The aim of this study was to compare the efficacy of pre-adjusted three-dimensional (3D) plating system employing 3D printing with conventional 3D plating in the management of mandibular fractures.

Materials And Methods: A randomised, clinical trial was conducted where the study sample ( = 20) was divided into two groups. In Group 1, 3D plate and in Group 2, pre-bent 3D plate was fixed to the fracture site.

Fusogenic liposome-coated nanoparticles for rapid internalization into donor corneal endothelial tissue to enable prophylaxis before transplantation.

Cold stress (hypothermia) during storage and cytokine stress due to acute allograft rejection adversely affect the donor corneal endothelium in the short term. Pharmacological pre-treatment (before transplantation) of the donor corneal endothelium or cells (propagated for cell injection therapy) with microtubule stabilizers, cold stress protectants, and other molecules is an attractive strategy to tackle damage caused by hypothermia and cytokine stress. These molecules can be delivered intracellularly to the donor corneal endothelium or cells at controlled rates for desired periods and with one-time administration using nanoparticles.

Grading the Severity of Damage to the Perijunctional Actomyosin Ring and Zonula Occludens-1 of the Corneal Endothelium by Ensemble Learning Methods.

In many epithelia, including the corneal endothelium, intracellular/extracellular stresses break down the perijunctional actomyosin ring (PAMR) and zonula occludens-1 (ZO-1) at the apical junctions. This study aims to grade the severity of damage to PAMR and ZO-1 through machine learning. Immunocytochemical images of PAMR and ZO-1 were drawn from recent studies on the corneal endothelium subjected to hypothermia and oxidative stress.

Evaluation of suitability and detection range of fluorescent dye-loaded nanoliposomes for sensitive and rapid sensing of wide ranging osmolarities.

Measurement of osmolarity is critical for optimizing bioprocesses including antibody production and detecting pathologies. Thus, rapid, sensitive, and sensing of osmolarity is desirable. This study aims to develop and assess the suitability of calcein- and sulforhodamine-loaded nanoliposomes for ratiometric sensing of osmolarity by fluorescence spectroscopy and evaluate the range of detection.

Experimental Oxidative Stress Breaks Down the Barrier Function of the Corneal Endothelium.

The fluid pump and barrier functions of the corneal endothelium maintain stromal deturgescence required for corneal transparency. The effect of oxidative stress, a hallmark of Fuchs endothelial corneal dystrophy (FECD), on the endothelial barrier function has been investigated. The endothelium of porcine corneas was exposed to (1) membrane permeable oxidants (HO, 100 μM, 1 h; tert-butyl-hydroperoxide, 100 μM, 1 h), or (2) ultraviolet A (UVA) with photosensitizers for 15 min, riboflavin (50 μM) or tryptophan (Trp) (100 μM).

Nanoliposomes for Sensing Local Osmolarity of the Tear Film on the Corneal Surface.

Local hotspots of elevated tear hyperosmolarity (exceeding 900 mOsM) are predicted in dry eye disease (DED) but have not been measured. This study aims to develop, characterize, and evaluate the suitability of fluorescent nanoliposomes for noninvasive sensing of the local osmolarity of the tear film. Fluorescent nanoliposomes, loaded with calcein (susceptible to self-quenching; sensor dye) and sulforhodamine 101 (SR101; reference dye), were produced by the thin-film hydration method.

Survival of Dental Implants on Irradiated Jaws: A Systematic Review and Meta-analysis.

Objectives: Dental implants play a significant role in functional rehabilitation of the oral cavity after debilitating jaw surgeries for oral cavity cancers followed by radiotherapy.

Design: The meta-analysis was done using Preferred Reporting Items for Systematic Review (PRISMA) guidelines published from January 1947 till August 2020. Twenty three articles consisting of 1246 participants with 4838 implants were included in our analysis.

An In Vitro Evaluation of a Novel Design Plate for Fixation of Mandibular Symphysis and Parasymphysis Fractures-A Finite Element Analysis.

Aim: Surgical management of mandibular symphysis and parasymphysis fractures has evolved from rigid fixation to semi-rigid fixation with miniplate osteosynthesis. Various miniplate systems have been developed in recent years including three-dimensional miniplate, microplates and bioresorbable plate, and their advantages and disadvantages have been compared and studied. To overcome the shortcomings of 3D plating system such as difficulty in adaptation and fixation in fractures involving the mental nerve, a novel plate has been designed by our institute.

Role of Oxidative Stress in the Disruption of the Endothelial Apical Junctional Complex During Corneal Cold Storage.

To characterize the impact of corneal cold storage (CS) on the endothelial apical junctional complex (AJC). Porcine corneas were held in CS (4°C; 1-7 days) with Cornisol™ preservation medium supplemented with epothilone B (EpoB; microtubule stabilizer; 100 nM), SB-203580 (p38 mitogen-activated protein [MAP] kinase inhibitor; 20 μM), or antioxidants (quercetin, 100 μM; vitamin E, 1 mM; deferoxamine, an iron chelator, 10 mM). After CS termination, the damage to endothelial AJC was characterized by imaging perijunctional actomyosin ring (PAMR) and zonula occludens (ZO-1).

Oxidative Stress Induces a Breakdown of the Cytoskeleton and Tight Junctions of the Corneal Endothelial Cells.

To investigate the impact of oxidative stress, which is a hallmark of Fuchs dystrophy, on the barrier function of the corneal endothelial cells. Experiments were carried out with cultured bovine and porcine corneal endothelial cells. For oxidative stress, cells were supplemented with riboflavin (Rf) and exposed to UV-A (15-30 min) to induce Type-1 photochemical reactions that release HO.

STimulator of INterferon Genes Agonism Accelerates Antitumor Activity in Poorly Immunogenic Tumors.

The innate immune agonist STING (STimulator of INterferon Genes) binds its natural ligand 2'3'-cGAMP (cyclic guanosine-adenosine monophosphate) and initiates type I IFN production. This promotes systemic antigen-specific CD8 T-cell priming that eventually provides potent antitumor activity. To exploit this mechanism, we synthesized a novel STING agonist, MSA-1, that activates both mouse and human STING with higher potency than cGAMP.

Microtubule Stabilization Protects Hypothermia-Induced Damage to the Cytoskeleton and Barrier Integrity of the Corneal Endothelial Cells.

To determine the impact of hypothermia on the barrier function of donor corneal endothelium, thereby enhancing the success of corneal transplantation. Primary cultures of porcine endothelial cells were subjected to hypothermia (15 h; 4°C). The impact on microtubule assembly, peri-junctional actomyosin ring (PAMR), and ZO-1 was assessed by immunocytochemistry with and without pretreatment with a microtubule-stabilizing agent (Epothilone B; EpoB; 100 nM) and a p38 MAP kinase inhibitor (SB-203580; 20 μM).

Discovery of Diaminopyrimidine Carboxamide HPK1 Inhibitors as Preclinical Immunotherapy Tool Compounds.

Hematopoietic progenitor kinase 1 (HPK1), a serine/threonine kinase, is a negative immune regulator of T cell receptor (TCR) and B cell signaling that is primarily expressed in hematopoietic cells. Accordingly, it has been reported that HPK1 loss-of-function in HPK1 kinase-dead syngeneic mouse models shows enhanced T cell signaling and cytokine production as well as tumor growth inhibition , supporting its value as an immunotherapeutic target. Herein, we present the structurally enabled discovery of novel, potent, and selective diaminopyrimidine carboxamide HPK1 inhibitors.

Combination of EP antagonist MF-766 and anti-PD-1 promotes anti-tumor efficacy by modulating both lymphocytes and myeloid cells.

Prostaglandin E (PGE), an arachidonic acid pathway metabolite produced by cyclooxygenase (COX)-1/2, has been shown to impair anti-tumor immunity through engagement with one or more E-type prostanoid receptors (EP). Specific targeting of EP receptors, as opposed to COX-1/2 inhibition, has been proposed to achieve preferential antagonism of PGE-mediated immune suppression. Here we describe the anti-tumor activity of MF-766, a potent and highly selective small-molecule inhibitor of the EP receptor.

ILT3 (LILRB4) Promotes the Immunosuppressive Function of Tumor-Educated Human Monocytic Myeloid-Derived Suppressor Cells.

Myeloid-derived suppressor cells (MDSC) are immature myeloid cells that accumulate in the tumor microenvironment (TME). MDSCs have been shown to dampen antitumor immune responses and promote tumor growth; however, the mechanisms of MDSC induction and their role in promoting immune suppression in cancer remain poorly understood. Here, we characterized the phenotype and function of monocytic MDSCs (M-MDSC) generated by coculture of human peripheral blood mononuclear cells with SK-MEL-5 cancer cells .

Pharmacological inhibition of hematopoietic progenitor kinase 1 positively regulates T-cell function.

Hematopoietic progenitor kinase 1 (HPK1), a hematopoietic cell-specific Ste20-related serine/threonine kinase, is a negative regulator of signal transduction in immune cells, including T cells, B cells, and dendritic cells (DCs). In mice, HPK1 deficiency subverts inhibition of the anti-tumor immune response and is associated with functional augmentation of anti-tumor T cells. We have used a potent, small molecule HPK1 inhibitor, Compound 1, to investigate the effects of pharmacological intervention of HPK1 kinase activity in immune cells.

Microparticle Encapsulation of a Prostate-targeted Biologic for the Treatment of Liver Metastases in a Preclinical Model of Castration-resistant Prostate Cancer.

PRX302 is a highly potent, mutant bacterial pore-forming biologic protoxin engineered for selective activation by PSA, a serine protease expressed by benign and malignant prostate epithelial cells. Although being developed as a local therapy for benign prostatic hyperplasia and localized prostate cancer, PRX302 cannot be administered systemically as a treatment for metastatic disease due to binding to ubiquitously expressed glycosylphosphatidylinositol (GPI)-anchored proteins, which leads to poor accumulation within the tumor microenvironment. To overcome this limitation, poly-lactic-co-glycolic acid (PLGA) microparticles encapsulating the protoxin were developed, which are known to accumulate in the liver, a major site of metastasis for prostate cancer and other solid tumors.

Development of High-Throughput Assays for Evaluation of Hematopoietic Progenitor Kinase 1 Inhibitors.

Hematopoietic progenitor kinase 1 (HPK1), also referred to as mitogen-activated protein kinase kinase kinase kinase 1 (MAP4K1), is a serine/threonine kinase that negatively regulates T-cell signaling by phosphorylating Ser376 of Src homology 2 (SH2) domain-containing leukocyte protein of 76 kDa (SLP-76), a critical mediator of T-cell receptor activation. HPK1 loss of function mouse models demonstrated enhanced immune cell activation and beneficial antitumor activity. To enable discovery and functional characterization of high-affinity small-molecule HPK1 inhibitors, we have established high-throughput biochemical, cell-based, and novel pharmacodynamic (PD) assays.

Studies on the use of sodium polyacrylate (SPA) for low-salt animal skin preservation.

Salt-based preservation is practiced for decades in the leather industry because of its versatility, cost-effectiveness, and availability. The salt removed from the soaking process causes significant pollution including organic and elevated total dissolved solids (TDS). Hence, a low-salt skin preservation method using commercial sodium polyacrylate with a reduced quantity of sodium chloride aiming to retain leather properties and pollution reduction was the principal focus of the study.

Prevention and Treatment of Multidrug-Resistant Organisms in End-Stage Renal Disease.

Chronic kidney disease patients are at high risk for infections because of multidrug-resistant organisms. Infections are the second most common cause of death in patients with ESRD. Patients with ESRD are prone to infections given alterations in immunity, increased rates of colonization with multidrug-resistant organisms, increased hospitalizations, and interactions with health care systems.

Bioengineered cellular and cell membrane-derived vehicles for actively targeted drug delivery: So near and yet so far.

Cellular carriers for drug delivery are attractive alternatives to synthetic nanoparticles owing to their innate homing/targeting abilities. Here, we review molecular interactions involved in the homing of Mesenchymal stem cells (MSCs) and other cell types to understand the process of designing and engineering highly efficient, actively targeting cellular vehicles. In addition, we comprehensively discuss various genetic and non-genetic strategies and propose futuristic approaches of engineering MSC homing using micro/nanotechnology and high throughput small molecule screening.