Cannabidiol Exerts Anticonvulsant Effects Alone and in Combination with Δ-THC through the 5-HT1A Receptor in the Neocortex of Mice.

Cannabinoids have shown potential in drug-resistant epilepsy treatment; however, we lack knowledge on which cannabinoid(s) to use, dosing, and their pharmacological targets. This study investigated (i) the anticonvulsant effect of Cannabidiol (CBD) alone and (ii) in combination with Delta-9 Tetrahydrocannabinol (Δ-THC), as well as (iii) the serotonin (5-HT)1A receptor's role in CBD's mechanism of action. Seizure activity, induced by 4-aminopyridine, was measured by extracellular field recordings in cortex layer 2/3 of mouse brain slices.

Sex-related differences in patient characteristics, and efficacy and safety of advanced therapies in randomised clinical trials in psoriatic arthritis: a systematic literature review and meta-analysis.

Background: Sex-related differences in clinical manifestations and disease outcomes exist in psoriatic arthritis, however, there is limited information on sex-related differences in randomised controlled trials of psoriatic arthritis. We aimed to compare patient characteristics and efficacy and safety of advanced therapies (including biological and targeted synthetic therapies) between male and female patients with psoriatic arthritis participating in randomised controlled trials.

Methods: In this systematic review and meta-analysis, we searched Medline, Embase, and Central databases, and conference abstract archives, from their inception to June 10, 2022, for randomised controlled trials that assessed the efficacy of advanced therapies in psoriatic arthritis.

Palmitate-induced insulin resistance causes actin filament stiffness and GLUT4 mis-sorting without altered Akt signalling.

Skeletal muscle insulin resistance, a major contributor to type 2 diabetes, is linked to the consumption of saturated fats. This insulin resistance arises from failure of insulin-induced translocation of glucose transporter type 4 (GLUT4; also known as SLC2A4) to the plasma membrane to facilitate glucose uptake into muscle. The mechanisms of defective GLUT4 translocation are poorly understood, limiting development of insulin-sensitizing therapies targeting muscle glucose uptake.

The resolution of phagosomes.

Phagocytosis is a fundamental immunobiological process responsible for the removal of harmful particulates. While the number of phagocytic events achieved by a single phagocyte can be remarkable, exceeding hundreds per day, the same phagocytic cells are relatively long-lived. It should therefore be obvious that phagocytic meals must be resolved in order to maintain the responsiveness of the phagocyte and to avoid storage defects.

Is Using Closed Incision Negative Pressure Therapy in Reconstructive and Oncoplastic Breast Surgery Helpful in Reducing Skin Necrosis?

Introduction Skin necrosis is a major concern of morbidity in patients undergoing reconstructive and oncoplastic breast surgery (ROBS) as it may lead to a poor aesthetic outcome, necessitate further surgery, and delay adjuvant chemotherapy and radiotherapy if required postoperatively. Some studies have reported that closed incision negative pressure therapy (ciNPT) immediately after surgery can reduce the incidence of wound complications. Our study aimed to investigate the effect of ciNPT on skin necrosis rate after ROBS.

Junctional integrity and directional mobility of lymphatic endothelial cell monolayers are disrupted by saturated fatty acids.

The lymphatic circulation regulates transfer of tissue fluid and immune cells toward the venous circulation. While obesity impairs lymphatic vessel function, the contribution of lymphatic endothelial cells (LEC) to metabolic disease phenotypes is poorly understood. LEC of lymphatic microvessels are in direct contact with the interstitial fluid, whose composition changes during the development of obesity, markedly by increases in saturated fatty acids.

Cohort profile of the Sloane Project: methodology for a prospective UK cohort study of >15 000 women with screen-detected non-invasive breast neoplasia.

Purpose: The introduction of breast screening in the UK led to an increase in the detection of non-invasive breast neoplasia, predominantly ductal carcinoma in situ (DCIS), a non-obligatory precursor of invasive breast cancer. The Sloane Project, a UK prospective cohort study of screen-detected non-invasive breast neoplasia, commenced in 2003 to evaluate the radiological assessment, surgical management, pathology, adjuvant therapy and outcomes for non-invasive breast neoplasia. Long-term follow-up and accurate data collection are essential to examine the clinical impact.

The presentation, management and outcome of patients with ductal carcinoma in situ (DCIS) with microinvasion (invasion ≤1 mm in size)-results from the UK Sloane Project.

Background: The diagnosis, management and prognosis of microinvasive breast carcinoma remain controversial.

Methods: We analysed the outcomes of patients with DCIS with and without microinvasion diagnosed between 2003 and 2012 within the Sloane project.

Results: Microinvasion was recorded in 521 of 11,285 patients (4.

Results of shared learning of a new magnetic seed localisation device - A UK iBRA-NET breast cancer localisation study.

Introduction: Shared learning is imperative in the assessment and safe implementation of new healthcare interventions. Magnetic seeds (Magseed®) potentially offer logistical benefit over wire localisation for non-palpable breast lesions but few data exist on outcomes comparing these techniques. A national registration study (iBRA-NET) was conducted to collate device outcomes.

The spectrin cytoskeleton integrates endothelial mechanoresponses.

Physiological blood flow induces the secretion of vasoactive compounds, notably nitric oxide, and promotes endothelial cell elongation and reorientation parallel to the direction of applied shear. How shear is sensed and relayed to intracellular effectors is incompletely understood. Here, we demonstrate that an apical spectrin network is essential to convey the force imposed by shear to endothelial mechanosensors.

Wire- and magnetic-seed-guided localization of impalpable breast lesions: iBRA-NET localisation study.

Background: Wire localization is historically the most common method for guiding excision of non-palpable breast lesions, but there are limitations to the technique. Newer technologies such as magnetic seeds may allow some of these challenges to be overcome. The aim was to compare safety and effectiveness of wire and magnetic seed localization techniques.

Unresected screen-detected ductal carcinoma in situ: Outcomes of 311 women in the Forget-Me-Not 2 study.

Background And Aim: The natural history of ductal carcinoma in situ (DCIS) is poorly understood. The aim of this cohort study was to determine the outcomes of women who had no surgery for screen-detected DCIS in the 6 months following diagnosis.

Methods: English breast screening databases were retrospectively searched for women diagnosed with DCIS without invasive cancer at screening and who had no record of surgery within 6 months of diagnosis.

ARPC1B binds WASP to control actin polymerization and curtail tonic signaling in B cells.

Immune cells exhibit low-level, constitutive signaling at rest (tonic signaling). Such tonic signals are required for fundamental processes, including the survival of B lymphocytes, but when they are elevated by genetic or environmental causes, they can lead to autoimmunity. Events that control ongoing signal transduction are, therefore, tightly regulated by submembrane cytoskeletal polymers like F-actin.

Altered neocortical oscillations and cellular excitability in an in vitro Wwox knockout mouse model of epileptic encephalopathy.

Loss of function mutations of the WW domain-containing oxidoreductase (WWOX) gene are associated with severe and fatal drug-resistant pediatric epileptic encephalopathy. Epileptic seizures are typically characterized by neuronal hyperexcitability; however, the specific contribution of WWOX to that hyperexcitability has yet to be investigated. Using a mouse model of neuronal Wwox-deletion that exhibit spontaneous seizures, in vitro whole-cell and field potential electrophysiological characterization identified spontaneous bursting activity in the neocortex, a marker of the underlying network hyperexcitability.

In Vivo Neocortical [K]o Modulation by Targeted Stimulation of Astrocytes.

A normally functioning nervous system requires normal extracellular potassium ion concentration ([K]o). Throughout the nervous system, several processes, including those of an astrocytic nature, are involved in [K]o regulation. In this study we investigated the effect of astrocytic photostimulation on [K]o.

The cytoskeleton in phagocytosis and macropinocytosis.

Cells of the innate immune system, notably macrophages, neutrophils and dendritic cells, perform essential antimicrobial and homeostatic functions. These functions rely on the dynamic surveillance of the environment supported by the formation of elaborate membrane protrusions. Such protrusions - pseudopodia, lamellipodia and filopodia - facilitate the sampling of the surrounding fluid by macropinocytosis, as well as the engulfment of particulates by phagocytosis.

A Novel Mixed-Methods Platform Study Protocol for Investigating New Surgical Devices, with Embedded Shared Learning: Ibra-net Breast Lesion Localisation Study.

Introduction: New medical devices must have adequate research, such that outcomes are known, enabling patients to be consented with knowledge of the safety and efficacy of the device to be implanted. Device trials are challenging due to the learning curve and iterative assessment of best practice. This study is designed to pilot a national collaborative approach to medical device introduction by breast surgeons in the UK, using breast localisation devices as an exemplar.

The use of genomic assays reduces rates of chemotherapy: a single-institution experience.

Introduction: The National Institute for Clinical Excellence recommends the use of tumour profiling tests to guide adjuvant chemotherapy in breast cancer. The Oncotype DX™ score (Genomic Health) has superseded more traditional tools such as PREDICT in appropriate patients (ER + ve, HER2-ve, lymph node negative and with a Nottingham Prognostic Index [NPI] ≥ 3.4).

Outcome of complete acellular dermal matrix wrap with polyurethane implant in immediate prepectoral breast reconstruction.

Background: Polyurethane implants have been used on and off in breast reconstruction since 1991 while prepectoral breast reconstruction has gained popularity in recent times. In this study, we present our outcomes from the use of acellular dermal matrix (ADM) complete wrap with polyurethane implants in prepectoral breast reconstruction.

Methods: This is a retrospective review of prospectively maintained database from 41 patients receiving complete ADM wrap with prepectoral polyurethane implants over a 3-year period.

C-terminus of Hsp70 Interacting Protein (CHIP) and Neurodegeneration: Lessons from the Bench and Bedside.

Neurodegenerative diseases are characterized by the increasing dysfunction and death of neurons, resulting in progressive impairment of a person's mobility and/or cognition. Protein misfolding and aggregation are commonly hypothesized to cause neurotoxicity and, eventually, neuronal degeneration that are associated with these diseases. Emerging experimental evidence, as well as recent findings from human studies, reveal that the C-terminus of Hsp70 Interacting Protein (CHIP), or STIP1 Homology and U-box containing Protein 1 (STUB1), is a quality control protein involved in neurodegeneration.

Stabilization of Endothelial Receptor Arrays by a Polarized Spectrin Cytoskeleton Facilitates Rolling and Adhesion of Leukocytes.

Multivalent complexes of endothelial adhesion receptors (e.g., selectins) engage leukocytes to orchestrate their migration to inflamed tissues.

Lipid-gated monovalent ion fluxes regulate endocytic traffic and support immune surveillance.

Despite ongoing (macro)pinocytosis of extracellular fluid, the volume of the endocytic pathway remains unchanged. To investigate the underlying mechanism, we used high-resolution video imaging to analyze the fate of macropinosomes formed by macrophages in vitro and in situ. Na, the primary cationic osmolyte internalized, exited endocytic vacuoles via two-pore channels, accompanied by parallel efflux of Cl and osmotically coupled water.

Phagolysosome resolution requires contacts with the endoplasmic reticulum and phosphatidylinositol-4-phosphate signalling.

Phosphoinositides have a pivotal role in the maturation of nascent phagosomes into microbicidal phagolysosomes. Following degradation of their contents, mature phagolysosomes undergo resolution, a process that remains largely uninvestigated. Here we studied the role of phosphoinositides in phagolysosome resolution.

Short-term safety outcomes of mastectomy and immediate implant-based breast reconstruction with and without mesh (iBRA): a multicentre, prospective cohort study.

Background: Use of biological or synthetic mesh might improve outcomes of immediate implant-based breast reconstruction-breast reconstruction with implants or expanders at the time of mastectomy-but there is a lack of high-quality evidence to support the safety or effectiveness of the technique. We aimed to establish the short-term safety of immediate implant-based breast reconstruction performed with and without mesh, to inform the feasibility of undertaking a future randomised clinical trial comparing different breast reconstruction techniques.

Methods: In this prospective, multicentre cohort study, we consecutively recruited women aged 16 years or older who had any type of immediate implant-based breast reconstruction for malignancy or risk reduction, with any technique, at 81 participating breast and plastic surgical units in the UK.

Contributions of the Hippocampal CA3 Circuitry to Acute Seizures and Hyperexcitability Responses in Mouse Models of Brain Ischemia.

The hippocampal circuitry is widely recognized as susceptible to ischemic injury and seizure generation. However, hippocampal contribution to acute non-convulsive seizures (NCS) in models involving middle cerebral artery occlusion (MCAO) remains to be determined. To address this, we occluded the middle cerebral artery in adult C57 black mice and monitored electroencephalographic (EEG) discharges from hippocampal and neocortical areas.