The Surveillance Strategy for Intraductal Pancreatic Mucinous Neoplasms: Criteria for Discontinuation.

Objective: To review the surveillance of IPMN, the risk of pancreatic cancer and the cost of surveillance.

Background: The increasing IPMN prevalence and low pancreatic cancer associated with IPMN question the necessity and cost-effectiveness of surveillance. Guidelines favour a 'watch and wait' approach, lacking clarity on stopping surveillance.

Identification of the interfacial regions in misfolded transthyretin oligomers.

Misfolding and aggregation of transthyretin (TTR) is associated with numerous ATTR amyloidosis. TTR aggregates extracted from ATTR patients consist of not only full-length TTR, but also N-terminally truncated TTR fragments that can be produced by proteolytic cleavage, suggesting the presence of multiple misfolding pathways. Here, we report mechanistic studies of an early stage of TTR aggregation to probe the oligomerization process for the full-length as well as N-terminally truncated TTR.

PLGA-Chitosan Encapsulated IL-10 Nanoparticles Modulate Chlamydia Inflammation in Mice.

Introduction: Interleukin-10 (IL-10) is a key anti-inflammatory mediator in protecting host from over-exuberant responses to pathogens and play important roles in wound healing, autoimmunity, cancer, and homeostasis. However, its application as a therapeutic agent for biomedical applications has been limited due to its short biological half-life. Therefore, it is important to prolong the half-life of IL-10 to replace the current therapeutic application, which relies on administering large and repeated dosages.

FIT for purpose: study protocol for a randomized controlled trial to personalize surveillance colonoscopy for individuals at elevated risk of colorectal cancer.

Purpose: There is increasing demand for colorectal cancer (CRC) surveillance, but healthcare capacity is limited. The burden on colonoscopy resources could be reduced by personalizing surveillance frequency using the fecal immunochemical test (FIT). This study will determine the safety, cost-effectiveness, and patient acceptance of using FIT to extend surveillance colonoscopy intervals for individuals at elevated risk of CRC.

Toxic Misfolded Transthyretin Oligomers with Different Molecular Conformations Formed through Distinct Oligomerization Pathways.

Protein aggregation is initiated by structural changes from native polypeptides to cytotoxic oligomers, which form cross-β structured amyloid. Identification and characterization of oligomeric intermediates are critically important for understanding not only the molecular mechanism of aggregation but also the cytotoxic nature of amyloid oligomers. Preparation of misfolded oligomers for structural characterization is, however, challenging because of their transient, heterogeneous nature.

Uniqueness of RNA Coliphage Qβ Display System in Directed Evolutionary Biotechnology.

Phage display technology involves the surface genetic engineering of phages to expose desirable proteins or peptides whose gene sequences are packaged within phage genomes, thereby rendering direct linkage between genotype with phenotype feasible. This has resulted in phage display systems becoming invaluable components of directed evolutionary biotechnology. The M13 is a DNA phage display system which dominates this technology and usually involves selected proteins or peptides being displayed through surface engineering of its minor coat proteins.

Lipopolysaccharide Administration Alters Extracellular Vesicles in Cell Lines and Mice.

Extracellular vesicles (EVs) play a fundamental role in cell and infection biology and have the potential to act as biomarkers for novel diagnostic tools. In this study, we explored the in vitro impact of bacterial lipopolysaccharide administration on cell lines that represents a target for bacterial infection in the host. Administration of lipopolysaccharide at varying concentrations to A549 and BV-2 cell lines caused only modest changes in cell death, but EV numbers were significantly changed.

Features associated with high-risk sessile serrated polyps at index and follow-up colonoscopy.

Background And Aim: Clinically significant serrated polyps are precursors of colorectal cancers, with features considered high risk including size ≥10 mm, dysplasia, and presence of synchronous conventional adenoma. While these features have been described in cohorts undergoing screening colonoscopy, there is little information regarding the prevalence and patient characteristics associated with high-risk sessile serrated polyps (SSPs) in those undergoing surveillance colonoscopy.

Methods: Polyp pathology at the index and first follow-up colonoscopy performed between 2004 and 2019 were examined in patients enrolled in a surveillance program because of an index finding of adenoma and/or SSP.

A nanovaccine formulation of Chlamydia recombinant MOMP encapsulated in PLGA 85:15 nanoparticles augments CD4 effector (CD44 CD62L) and memory (CD44 CD62L) T-cells in immunized mice.

Vaccine developmental strategies are utilizing antigens encapsulated in biodegradable polymeric nanoparticles. Here, we developed a Chlamydia nanovaccine (PLGA-rMOMP) by encapsulating its recombinant major outer membrane protein (rMOMP) in the extended-releasing and self-adjuvanting PLGA [poly (D, L-lactide-co-glycolide) (85:15)] nanoparticles. PLGA-rMOMP was small (nanometer size), round and smooth, thermally stable, and exhibited a sustained release of rMOMP.

Transfection of glycoprotein encoding mRNA for swift evaluation of N-glycan engineering strategies.

N-glycosylation is defined as a key quality attribute for the majority of complex biological therapeutics. Despite many N-glycan engineering efforts, the demand to generate desired N-glycan profiles that may vary for different proteins in a reproducible manner is still difficult to fulfill in many cases. Stable production of homogenous structures with a more demanding level of processing, for instance high degrees of branching and terminal sialylation, is particularly challenging.

Effects of on Microglial-Derived Extracellular Vesicle Biogenesis and Composition.

The packaging of molecular constituents inside extracellular vesicles (EVs) allows them to participate in intercellular communication and the transfer of biological molecules, however the role of EVs during bacterial infection is poorly understood. The goal of this study was to examine the effects of ( infection on the biogenesis and composition of EVs derived from the mouse microglia cell line, BV-2. BV-2 cells were cultured in exosome-free media and infected with 0, 1.

mRNA Transfection into CHO-Cells Reveals Production Bottlenecks.

Obtaining highly productive Chinese hamster ovary (CHO)-cell clones for the production of therapeutic proteins relies on multiple time-consuming selection steps. Several CHO-cell strains with high degrees of genomic and epigenetic variation are available. Each harbor potential advantages and disadvantages for any given product, particularly those considered difficult to express.

Function of the RNA Coliphage Qβ Proteins in Medical In Vitro Evolution.

Qβ is a positive (+) single-stranded RNA bacteriophage covered by a 25 nm icosahedral shell. Qβ belongs to the family of Leviviridae and is found throughout the world (bacterial isolates and sewage). The genome of Qβ is about 4.

Sessile Serrated Polyps with Synchronous Conventional Adenomas Increase Risk of Future Advanced Neoplasia.

Background: Surveillance colonoscopy guidelines following adenomas or sessile serrated adenomas/polyps (SSPs) are based on pathology features known to be associated with risk of future colorectal cancer. A synchronous conventional adenoma may increase the malignant potential of SSP, but current guidelines do not address this combination of pathologies.

Aims: The aim was to assess the risk of advanced neoplasia after SSP with or without synchronous adenoma compared to that following a conventional adenoma.

Does time of surgery influence the rate of false-negative appendectomies? A retrospective observational study of 274 patients.

Background: Multiple disciplines have described an "after-hours effect" relating to worsened mortality and morbidity outside regular working hours. This retrospective observational study aimed to evaluate whether diagnostic accuracy of a common surgical condition worsened after regular hours.

Methods: Electronic operative records for all non-infant patients (age > 4 years) operated on at a single centre for presumed acute appendicitis were retrospectively reviewed over a 56-month period (06/17/2012-02/01/2017).

Hyperencapsulated mucoid pneumococcal isolates from patients with cystic fibrosis have increased biofilm density and persistence in vivo.

Mucoid bacteria, predominately Pseudomonas aeruginosa, are commonly associated with decline in pulmonary function in children with cystic fibrosis (CF), and are thought to persist at least in part due to a greater propensity toward forming biofilms. We isolated a higher frequency of mucoid Streptococcus pneumoniae (Sp) expressing high levels of capsular polysaccharides from sputa from children with CF, compared to those without CF. We compared biofilm formation and maturation by mucoid and non-mucoid isolates of Sp collected from children with and without CF.

A multispecialty study of determining the possibility of pregnancy and the documentation of pregnancy status in surgical patients: a cause for concern?

Background: Determining the possibility of pregnancy and the documentation of pregnancy status are important considerations in the assessment of females of reproductive age when admitted to hospital.

Objectives: Our aim was to determine the adequacy of the documentation of pregnancy status and possibility of pregnancy across multiple surgical specialties.

Materials And Methods: A prospective audit of surgical specialties (general, orthopaedics, urology, vascular, maxillofacial, ENT, gynaecology and neurosurgery) within NHS Tayside, in May 2015.

Pathogens and Their Effect on Exosome Biogenesis and Composition.

Exosomes are nanosized membrane microvesicles (30⁻100 nm) that have the capability to communicate intercellularly and transport cell components (i.e., miRNA, mRNA, proteins and DNA).

A nurse-led model at public academic hospitals maintains high adherence to colorectal cancer surveillance guidelines.

Objective: To examine the compliance of colorectal cancer surveillance decisions for individuals at greater risk with current evidence-based guidelines and to determine whether compliance differs between surveillance models.

Design: Prospective auditing of compliance of surveillance decisions with evidence-based guidelines (NHMRC) in two decision-making models: nurse coordinator-led decision making in public academic hospitals and physician-led decision making in private non-academic hospitals.

Setting: Selected South Australian hospitals participating in the Southern Co-operative Program for the Prevention of Colorectal Cancer (SCOOP).

The science of teams in the military: Contributions from over 60 years of research.

Teams are the foundational building blocks of the military, which uses a hierarchical structure built on and around teams to form larger units. Consequently, team effectiveness has been a substantial focus of research within the military for decades to ensure military teams have the human capabilities to complete their missions and address future challenges successfully. This research has contributed greatly to broader team theory and informed the development of evidence-based interventions.

OPP Labeling Enables Total Protein Synthesis Quantification in CHO Production Cell Lines at the Single-Cell Level.

Accurate measurement of global and specific protein synthesis rates is becoming increasingly important, especially in the context of biotechnological applications such as process modeling or selection of production cell clones. While quantification of total protein translation across whole cell populations is easily achieved, methods that are capable of tracking population dynamics at the single-cell level are still lacking. To address this need, we apply O-propargyl-puromycin (OPP) labeling to assess total protein synthesis in single recombinant Chinese hamster ovary (CHO) cells by flow cytometry.

Optogenetic control of focal adhesion kinase signaling.

Focal adhesion kinase (FAK) integrates signaling from integrins, growth factor receptors and mechanical stress to control cell adhesion, motility, survival and proliferation. Here, we developed a single-component, photo-activatable FAK, termed optoFAK, by using blue light-induced oligomerization of cryptochrome 2 (CRY2) to activate FAK-CRY2 fusion proteins. OptoFAK functions uncoupled from physiological stimuli and activates downstream signaling rapidly and reversibly upon blue light exposure.

The anti-microbial peptide TP359 attenuates inflammation in human lung cells infected with Pseudomonas aeruginosa via TLR5 and MAPK pathways.

Pseudomonas aeruginosa infection induces vigorous inflammatory mediators secreted by epithelial cells, which do not necessarily eradicate the pathogen. Nonetheless, it reduces lung function due to significant airway damage, most importantly in cystic fibrosis patients. Recently, we published that TP359, a proprietary cationic peptide had potent bactericidal effects against P.

Improving Animal Disease Detection Through an Enhanced Passive Surveillance Platform.

The ability to rapidly detect and report infectious diseases of domestic animals and wildlife is paramount to reducing the size and duration of an outbreak. There is currently a need in the United States livestock industry for a centralized animal disease surveillance platform, capable of collecting, integrating, and analyzing multiple data streams with dissemination to end-users. Such a system would be disease agnostic and establish baseline information on animal health and disease prevalence; it would alert health officials to anomalies potentially indicative of emerging and/or transboundary disease outbreaks, changes in the status of endemic disease, or detection of other causative agents (eg, toxins).