Immune Cells Activating Biotin-Decorated PLGA Protein Carrier.

Nanoparticle formulations have long been proposed as subunit vaccine carriers owing to their ability to entrap proteins and codeliver adjuvants. Poly(lactic--glycolic acid) (PLGA) remains one of the most studied polymers for controlled release and nanoparticle drug delivery, and numerous studies exist proposing PLGA particles as subunit vaccine carriers. In this work we report using PLGA nanoparticles modified with biotin (bNPs) to deliver proteins via adsorption and stimulate professional antigen-presenting cells (APCs).

'Mini-Max' knotless acetabular labrum repair: repair construct rationale and allocation in a consecutive case series with minimum 1-year clinical outcomes.

To describe the 'mini-Max' approach to labrum repair using non-absorbable 2.4-mm knotless suture anchors and report objective clinical outcomes with a large single-surgeon cohort. Level 3 retrospective case series.

Bacterial Identification and Visualization of Bacterial Biofilms Adjacent to Fracture Sites After Internal Fixation.

The primary aims of this study were to determine if any correlation exists in cases of fracture fixation among: (1) bacterial profiles recovered from the instrumentation and adjacent tissues; (2) the type of orthopedic injury; and (3) the clinical outcome-union versus nonunion. A secondary goal was to compare culture and molecular diagnostics for identifying the bacterial species present following fracture fixation. Single-institution, prospective case-control cohort study.

Closed cranial window rodent model for investigating hemodynamic response to elevated intracranial pressure.

Background: Elevated intracranial pressure (ICP) occurs in several physiological and pathological conditions, yet long-term sequellae are not common, which implies that blood flow is preserved above ischemic thresholds.

Methods: This pilot study sought to confirm this hypothesis using a closed cranial window model in a rat in which ICP was elevated to 120 mmHg for 12 min, and superficial cortical perfusion was measured by laser Doppler flowmetry and laser speckle flowmetry.

Results: Following a transient increase, cortical blood flow decreased to between 25% and 75% of baseline.

Flares after hydroxychloroquine reduction or discontinuation: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort.

Objectives: To evaluate systemic lupus erythematosus (SLE) flares following hydroxychloroquine (HCQ) reduction or discontinuation versus HCQ maintenance.

Methods: We analysed prospective data from the Systemic Lupus International Collaborating Clinics (SLICC) cohort, enrolled from 33 sites within 15 months of SLE diagnosis and followed annually (1999-2019). We evaluated person-time contributed while on the initial HCQ dose ('maintenance'), comparing this with person-time contributed after a first dose reduction, and after a first HCQ discontinuation.

Integrated Analysis of the Pancreas and Islets Reveals Unexpected Findings in Human Male With Type 1 Diabetes.

Clinical and pathologic heterogeneity in type 1 diabetes is increasingly being recognized. Findings in the islets and pancreas of a 22-year-old male with 8 years of type 1 diabetes were discordant with expected results and clinical history (islet autoantibodies negative, hemoglobin A1c 11.9%) and led to comprehensive investigation to define the functional, molecular, genetic, and architectural features of the islets and pancreas to understand the cause of the donor's diabetes.

Clinical Significance of Postoperative Antibiotic Treatment for Positive Islet Cultures After Total Pancreatectomy With Islet Autotransplantation.

Objectives: Islet cultures are routinely performed in total pancreatectomy with islet autotransplantation (TPIAT), and the need for empiric antibiotic treatment based on culture results is unknown. We evaluated the effect of postoperative antibiotic treatment for positive islet cultures on clinical infection.

Methods: Seventy-nine patients undergoing TPIAT were reviewed.

Combinatorial transcription factor profiles predict mature and functional human islet α and β cells.

Islet-enriched transcription factors (TFs) exert broad control over cellular processes in pancreatic α and β cells, and changes in their expression are associated with developmental state and diabetes. However, the implications of heterogeneity in TF expression across islet cell populations are not well understood. To define this TF heterogeneity and its consequences for cellular function, we profiled more than 40,000 cells from normal human islets by single-cell RNA-Seq and stratified α and β cells based on combinatorial TF expression.

Controls of Hyperglycemia Improves Dysregulated Microbiota in Diabetic Mice.

Background: Type 1 diabetes (T1DM) is a chronic autoimmune disease characterized by T-cell-mediated destruction of insulin-producing beta cells. Evidence shows that patients with T1DM and mice used in specific diabetic models both exhibit changes in their intestinal microbiota and dysregulated microbiota contributes to the pathogenesis of T1DM. Islet transplantation (Tx) is poised to play an important role in the treatment of T1DM.

Human Hemangioblast-Derived Mesenchymal Stem Cells Promote Islet Engraftment in a Minimal Islet Mass Transplantation Model in Mice.

Islet transplantation can restore glycemic control in patients with type 1 diabetes. Using this procedure, the early stages of engraftment are often crucial to long-term islet function, and outcomes are not always successful. Numerous studies have shown that mesenchymal stem cells (MSCs) facilitate islet graft function.

Chemically-Induced Cross-Linking of Peptidic Fibrils for Scaffolding Polymeric Particles and Macrophages.

EAK16-II (EAK) is a self-assembling peptide (SAP) that forms β-sheets and β-fibrils through ionic-complementary interactions at physiological ionic strengths. The soft materials can be injected in vivo, creating depots of drugs and cells for rendering pharmacological and biological actions. The scope of the applications of EAK is sought to extend to tissues through which the flow of extracellular fluid tends to be limited.

Depression Before and After a Diagnosis of Pancreatic Cancer: Results From a National, Population-Based Study.

Objectives: The aim of this study was to evaluate depression in pancreatic cancer (PC) patients before and after a cancer diagnosis using a US-based healthcare database. We also sought to study the impact of treatment of depression in PC patients on all-cause mortality.

Methods: Pancreatic cancer patients with comorbid depression in Explorys (1999-2019) were compared with controls using odds ratios with 95% confidence intervals.

Arthroscopic classification of intra-articular hip pathology demonstrates at best moderate interrater reliability.

Purpose: The purpose of this study was to report several novel classification systems for intra-articular lesions observed during hip arthroscopy, and to quantify the interrater reliability of both these novel systems and existing classifications of intra-articular lesions when tested by a group of high-volume hip arthroscopists.

Methods: Five hip arthroscopists deliberated over shortcomings in current classification systems and developed several novel grading systems with particular effort made to capture factors important to the treatment and outcomes of hip arthroscopy for labral injury. A video learning module describing the classifications was then developed from the video archive of surgeries performed by the senior author and reviewed by study participants.

Dapagliflozin Does Not Directly Affect Human α or β Cells.

Selective inhibitors of sodium glucose cotransporter-2 (SGLT2) are widely used for the treatment of type 2 diabetes and act primarily to lower blood glucose by preventing glucose reabsorption in the kidney. However, it is controversial whether these agents also act on the pancreatic islet, specifically the α cell, to increase glucagon secretion. To determine the effects of SGLT2 on human islets, we analyzed SGLT2 expression and hormone secretion by human islets treated with the SGLT2 inhibitor dapagliflozin (DAPA) in vitro and in vivo.

Decreased pancreatic acinar cell number in type 1 diabetes.

Aims/hypothesis: Individuals with longstanding and recent-onset type 1 diabetes have a smaller pancreas. Since beta cells represent a very small portion of the pancreas, the loss of pancreas volume in diabetes is primarily due to the loss of pancreatic exocrine mass. However, the structural changes in the exocrine pancreas in diabetes are not well understood.

Integrated human pseudoislet system and microfluidic platform demonstrate differences in GPCR signaling in islet cells.

Pancreatic islets secrete insulin from β cells and glucagon from α cells, and dysregulated secretion of these hormones is a central component of diabetes. Thus, an improved understanding of the pathways governing coordinated β and α cell hormone secretion will provide insight into islet dysfunction in diabetes. However, the 3D multicellular islet architecture, essential for coordinated islet function, presents experimental challenges for mechanistic studies of intracellular signaling pathways in primary islet cells.

Inguinal Subcutaneous White Adipose Tissue (ISWAT) Transplantation Model of Murine Islets.

Pancreatic islet transplantation is a well-established therapeutic treatment for type 1 diabetes. The kidney capsule is the most commonly used site for islet transplantation in rodent models. However, the tight kidney capsule limits the transplantation of sufficient islets in large animals and humans.

Tacrolimus- and sirolimus-induced human β cell dysfunction is reversible and preventable.

Posttransplantation diabetes mellitus (PTDM) is a common and significant complication related to immunosuppressive agents required to prevent organ or cell transplant rejection. To elucidate the effects of 2 commonly used agents, the calcineurin inhibitor tacrolimus (TAC) and the mTOR inhibitor sirolimus (SIR), on islet function and test whether these effects could be reversed or prevented, we investigated human islets transplanted into immunodeficient mice treated with TAC or SIR at clinically relevant levels. Both TAC and SIR impaired insulin secretion in fasted and/or stimulated conditions.

Unique Substantial Clinical Benefit Values for the 12-Item International Hip Outcome Tool Based on Preoperative Level of Function.

Purpose: To define unique substantial clinical benefit (SCB) values for improvement on the 12-item International Hip Outcome Tool (iHOT-12) based on a preoperative self-rating of function in patients undergoing hip arthroscopy for intra-articular pathology.

Methods: This was a retrospective review of prospective collected data on patients having hip arthroscopy for labral and chondral pathology and femoroacetabular impingement. On preoperative assessment and 1-year (+/-1 month) follow-up, subjects completed the iHOT-12 and a self-categorical rating of function ("severely abnormal," "abnormal," "nearly normal," or "normal").

Old new: Risk factors predicting early onset colorectal cancer.

Background: Colorectal cancer (CRC) is the second leading cause of all cancer related deaths in the United States and Europe. Although the incidence has been decreasing for individuals' ≥ 50, it has been on the rise for individuals < 50.

Aim: To identify potential risk factors for early-onset CRC.

A comparative study of three biomaterials in an ovine bone defect model.

Background: Polyetheretherketone (PEEK), and more recently titanium-coated PEEK, have been given serious consideration as biomaterial design choices for spinal interbody implants. Shortcomings in these materials necessitate further innovation into materials research, for example, on PEKK. Common complications such as surface delamination (as with titanium coating) and lack of bone apposition (as with PEEK) indicate the need for a new material that inherently displays preferable bone growth characteristics without sacrificing structural integrity.

Asparagine Synthetase Is Highly Expressed at Baseline in the Pancreas Through Heightened PERK Signaling.

Asparaginase (ASNase) causes pancreatitis in approximately 10% of leukemia patients, and the mechanisms underlying this painful complication are not known. ASNase primarily depletes circulating asparagine, and the endogenously expressed enzyme, asparagine synthetase (ASNS), replenishes asparagine. ASNS was suggested previously to be highly expressed in the pancreas.

Defining Pancreatitis as a Risk Factor for Pancreatic Cancer: The Role, Incidence, and Timeline of Development.

Objectives: Acute and/or chronic pancreatitis has been implicated as an important risk factor for pancreatic cancer; however, the incidence and temporal relationship of pancreatitis before pancreatic cancer diagnosis are unclear. We aim to understand the role and incidence of pancreatitis temporally with the development of pancreatic cancer.

Methods: A population-based study was used to investigate a temporal relationship between pancreatitis and pancreatic cancer diagnoses.

Is the renal subcapsular space the preferred site for clinical porcine islet xenotransplantation? Review article.

It can reasonably be anticipated that, within 5-10 years, islet allotransplantation or pig islet xenotransplantation may be the preferred options for β-cell replacement therapy. The portal vein/liver is currently the preferred clinical site for free islet transplantation, constituting 90% of clinical islet transplants. Despite being the site of choice for rodent and some large animal studies, the renal subcapsular space is rarely used clinically, even though the introduction of islets intraportally is not entirely satisfactory (particularly for pig islet xenotransplantation).