An optogenetic mouse model of hindlimb spasticity after spinal cord injury.

Spasticity is a common comorbidity of spinal cord injury (SCI), disrupting motor function and resulting in significant discomfort. While elements of post-SCI spasticity can be assessed using pre-clinical SCI models, the robust measurement of spasticity severity can be difficult due to its periodic and spontaneous appearance. Electrical stimulation of sensory afferents can elicit spasticity-associated motor responses, such as spasms; however, placing surface electrodes on the hindlimbs of awake animals can induce stress or encumbrance that could influence the expression of behaviour.

Electrophysiological signatures of the effect of context on exploration: Greater attentional and learning signals when exploration is costly.

Humans are excellent at modifying our behaviour depending on context. For example, humans will change how they explore when losses are possible compared to when they are not possible. However, it remains unclear what specific cognitive and neural processes are modulated when exploring in different contexts.

Sagittaria sagittifolia polysaccharide extract regulates Nrf2 to improve endoplasmic reticulum stress-mediated apoptosis in rat cataracts and HLEB3 cells.

Age-related cataract (ARC) remains the leading cause of blindness worldwide. Sagittaria sagittifolia polysaccharide (SSP) extract, a key component of Sagittaria sagittifolia L., exhibits anti-oxidant and anti-apoptotic effects with potential applications in ARC.

Advances in IgY antibody dosage form design and delivery strategies: Current status and future perspective.

Immunoglobulin Y (IgY), a unique type of antibody found in birds, is attracting increasing attention for a broad range of biomedical applications. Rational IgY protection, dosage form design, and delivery are highly essential to transform functional IgY antibodies into desired IgY products for therapeutic and prophylactic administration. Although progress has been made in this field, it remains in the early stages, highlighting the fundamental research and development needed in this aspect of IgY technology.

Heterologous expression of a recombinant ACE inhibitory peptide LYPVK and its potential antihypertensive action mechanism.

Enzymatic hydrolysis approach is commonly employed for preparation of active peptides, while the limited purity and yield of produced peptides hinder further development of action mechanisms. This study presents the biotechnological approach for the efficient production of recombinant angiotensin converting enzyme (ACE) inhibitory peptide LYPVK and investigates its potential antihypertensive action mechanism. DNA encoding sequence of recombinant peptide was designed to form in tandem, which was expressed in Escherichia coli BL21 (DE3).

Bacterial expression, purification and characterization of the human Dectin-1 lectin domain for structural and functional studies.

Dectin-1 (CLEC7A), a C-type lectin-like receptor that recognizes β-1,3 glucans, has a key role in the innate immune system. While the lectin domain of mouse Dectin-1 has been solubilized and refolded from inclusion bodies in Escherichia coli, similar refolding of the human Dectin-1 lectin domain is hindered by the formation of misfolded multimers with aberrant intermolecular disulfide bonds. The aim of this study was to develop a method for the large-scale production of the human Dectin-1 lectin domain.

Enhanced production of recombinant calf chymosin in Kluyveromyces lactis via CRISPR-Cas9 engineering.

As an important industrial enzyme, chymosin has been widely used in cheese manufacturing. Fermentation with Kluyveromyces lactis has allowed recombinant chymosin production to fit the growing global demand for cheese consumption; yet improvements can be made to allow for stable and larger-scale production. In this work, various chymosin producing (CP) strains were constructed via targeted chromosomal integration of various copies of a prochymosin expression cassette (PEC) using a CRISPR-Cas9 platform optimized for K.

Eccentric Reaming is Superior to Augmented Components in B2 Glenoids: a Biomechanical study.

Introduction: Primary glenohumeral arthritis is typically associated with glenoid retroversion and posterior bone loss. Glenoid component fixation remains a weak link in the survivorship of anatomical total shoulder arthroplasty, particularly in the B2 glenoid. The aim of this study was to compare biomechanical properties of two glenoid preparation techniques in a B2 glenoid bone loss model.

The risk of donor-acquired allergy in solid organ transplant recipients: a systematic review.

Background: Donor acquired allergy (DAA) occurs when donors transfer their allergies to recipients through solid organ transplant (SOT). However, the risk of DAA in recipients of organs from allergic donors has not been systematically characterized.

Objective: We sought to synthesize the available evidence on the risk of DAA in SOT recipients.

Feasibility and acceptability of the delivery of a group telehealth intervention for support persons of patients receiving buprenorphine for opioid use disorder.

Background: Opioid-related overdoses increased substantially during the COVID-19 pandemic, eliciting an urgent demand for accessible treatment for individuals with opioid use disorder (OUD) and those who support them (support persons). Support persons can improve treatment initiation and retention in their individuals with OUD. Additionally, support persons may have their own mental health needs related to their loved one's OUD.

Digital Profiling of Immune Biomarkers in Breast Cancer: Relation to Anthracycline Benefit.

Assessment of the tumor immune microenvironment can be used as a prognostic tool for improved survival and as a predictive biomarker for treatment benefit, particularly from immune modulating treatments including cytotoxic chemotherapy. Using Digital Spatial Profiling (DSP), we studied the tumor immune microenvironment of 522 breast cancer cases by quantifying 35 immune biomarkers on tissue microarrays from the MA.5 phase III clinical trial.

The juxtamembrane sequence of small ankyrin 1 mediates the binding of its cytoplasmic domain to SERCA1 and is required for inhibitory activity.

Sarcoplasmic/endoplasmic reticulum Ca-ATPase1 (SERCA1) is responsible for the clearance of cytosolic Ca in skeletal muscle. Due to its vital importance in regulating Ca homeostasis, the regulation of SERCA1 has been intensively studied. Small ankyrin 1 (sAnk1, Ank1.

Mechanisms of dual modulatory effects of spermine on the mitochondrial calcium uniporter complex.

The mitochondrial Ca uniporter is the Ca channel responsible for mitochondrial Ca uptake. It plays crucial physiological roles in regulating oxidative phosphorylation, intracellular Ca signaling, and cell death. The uniporter contains the pore-forming MCU subunit, the auxiliary EMRE protein, and the regulatory MICU1 subunit, which blocks the MCU pore under resting cellular Ca concentrations.

NUMB alternative splicing and isoform specific functions in development and disease.

The NUMB gene encodes a conserved adaptor protein with roles in asymmetric cell division and cell fate determination. First described as an inhibitor of Notch signaling, multi-functional NUMB proteins regulate multiple cellular pathways through protein complexes with ubiquitin ligases, polarity proteins and the endocytic machinery. The vertebrate NUMB protein isoforms were identified over two decades ago, yet the majority of functional studies exploring NUMB function in endocytosis, cell migration and adhesion, development and disease have largely neglected the potential for distinct isoform activity in design and interpretation.

Recombinant Antibodies Inhibit Enzymatic Activity of the E3 Ubiquitin Ligase CHIP via Multiple Mechanisms.

Carboxyl-terminus of Hsp70-Interacting Protein (CHIP) is an E3 ubiquitin ligase that marks misfolded substrates for degradation. Hyper-activation of CHIP has been implicated in multiple diseases, including cystic fibrosis and cancer, suggesting that it may be a potential drug target. However, there are few tools available for exploring this possibility.

P3 site-directed mutagenesis: An efficient method based on primer pairs with 3'-overhangs.

Site-directed mutagenesis is a fundamental tool indispensable for protein and plasmid engineering. An important technological question is how to achieve the efficiency at the ideal level of 100%. Based on complementary primer pairs, the QuickChange method has been widely used, but it requires significant improvements due to its low efficiency and frequent unwanted mutations.

Novel isoxazole thiophene-containing compounds active against Mycobacterium tuberculosis.

Screening of the ChemDiv molecular library in cholesterol media against Mycobacterium tuberculosis (Mtb) H37Rv strain identified a novel isoxazole thiophene hit as a putative Rv1625c/Cya activator with a promising in vitro activity and good pharmacokinetic properties. Twenty-nine analogs were synthesized to assess the structure-activity relationships (SAR) to further improve potency. The most notable analog was P15, which showed an intramacrophage EC = 1.

Mixed reality for preoperative planning and intraoperative assistance of surgical correction of complex congenital heart defects.

Objectives: Mixed reality (MixR) is an innovative visualization tool that presents virtual elements in a real-world environment, enabling real-time interaction between the user and the combined digital/physical reality. We aimed to explore the feasibility of MixR in enhancing preoperative planning and intraoperative guidance for the correction of various complex congenital heart defects (CHDs).

Methods: Patients underwent cardiac computed tomography or cardiac magnetic resonance and segmentation of digital imaging and communications in medicine (DICOM) images was performed.

Cyclosporine Treatment in Patients with Kawasaki Disease and Coronary Artery Aneurysms or Treatment Resistance.

Objective: To describe the clinical course and outcome of 33 patients with Kawasaki disease (KD) treated with cyclosporine (CSA) for coronary artery abnormalities (CAA) or treatment resistance.

Study Design: Single-center, retrospective study of patients with KD treated from 2013 through 2023 for CAA or treatment resistance. Demographics, laboratory studies, medications, adverse events, and echocardiographic data were analyzed.

Analysis of clinical features and prognosis in cardiac amyloidosis patients from Spanish hospitals (2016-2021).

Introduction And Objectives: Cardiac amyloidosis (CA) is a prevalent yet underdiagnosed heart condition characterized by the abnormal accumulation of amyloid fibres, frequently resulting in heart failure (HF), particularly in older people. Despite advancements in non-invasive diagnostic techniques and treatments, the epidemiology of CA patients remains inadequately understood. This nationwide retrospective observational study sought to comprehensively investigate CA patients' characteristics, mortality, and readmission patterns.

Longitudinal integrated proteomic and metabolomic skin changes in atopic dermatitis patients treated with dupilumab.

Background: Inhibition of IL-4/IL-13 driven inflammation by dupilumab has shown significant clinical benefits in treatment of atopic dermatitis (AD).

Objective: To assess longitudinal protein and metabolite composition in AD skin during dupilumab treatment.

Methods: Skin tape strip (STS) were collected from lesional/non-lesional skin of 20 AD patients during 16-week dupilumab treatment and from 20 healthy volunteers (HV) followed for 16-weeks.

Allergen-induced activation of epithelial P2Y receptors promotes ATP exocytosis and type 2 immunity in airways.

Background: Environmental allergens induce the release of danger signals from the airway epithelium that trigger type 2 immune responses and promote airway inflammation.

Objective: To investigate the role of allergen-stimulated P2Y receptor activation in regulating ATP, IL-33 and DNA release by human bronchial epithelial (hBE) cells and mouse airways.

Methods: hBE cells were exposed to Alternaria alternata extract and secretion of ATP, IL-33 and DNA were studied in vitro.

Long Term Results of a Comparative Study of Percutaneous and Surgically Created Proximal Forearm Arteriovenous Fistulae.

Objective: This retrospective, single centre, comparative effectiveness study aimed to compare the long term outcomes of percutaneous arteriovenous fistulae (pAVF) and surgically created arteriovenous fistulae (sAVF) created in the proximal forearm for haemodialysis access.

Methods: Data were reviewed from a prospectively maintained database on patients who underwent pAVF or sAVF creation from September 2017 to September 2023. A total of 217 pAVFs (61 WavelinQ and 156 Ellipsys) and 158 sAVFs were analysed.

Clinical Utility of Systolic Left Ventricular Ejection Fraction in Atrial Fibrillation: Role of Prospective ECG-Triggered Cardiac CT.

Background: The assessment of left ventricular (LV) systolic function and quantification of LV ejection fraction (EF) in patients with atrial fibrillation (AF) can be difficult. We previously demonstrated that LV volume changes over the 100 ms of systole (LVEF) can be used as a measure of LV systolic function.

Objective: We sought to evaluate the applicability of LVEF in AF patients.

Rationale and Design of the Prevail Global Trial Program Evaluating the Prevail Drug-Coated Balloon in Patients with In-stent Restenosis and De Novo Small Vessel Disease.

Background And Rationale: In-stent restenosis (ISR) remains the leading cause of treatment failure following percutaneous coronary intervention (PCI) with contemporary drug-eluting stents. Especially in small caliber coronary arteries, restenosis is common following PCI and represents a treatment challenge. Drug-coated balloons (DCB) are an attractive alternative to stents for treatment of both ISR and small vessel disease.