findings highlight Tfh and Tph-cells, IL-21 and the ICOS costimulatory pathway as key pathogenic players in SS immunopathology and exploitable therapeutic targets in SS.Nail bed avulsion injuries often require reconstruction, particularly in cases where the avulsed fragment is lost. We describe a simple way to reconstruct a large nail bed defect, with no donor site. A 13-year-old boy with a hypoplastic left heart and autism accidentally sustained a left little distal phalanx injury with an avulsion of 60% of the nail bed, exposing the distal phalanx. This boy had a history of poor compliance, qualifying the need to find a technique that would minimise operative time and dressing changes. As such, it was elected to use an acellular dermal matrix (ADM) (Matriderm) as a one-step reconstruction. Signs of vascularisation of the ADM were noted at 2 weeks, and 3-month follow-up demonstrated integration, with normal nail growth. We found that Matriderm was able to support the regeneration of a full thickness wound in a simple one-step procedure.A 59-year-old woman, a known case of hypertension, was incidentally diagnosed with a large right-sided adrenal mass. Investigations for a functional adrenal lesion resulted in very high preoperative norepinephrine levels. A right adrenalectomy was performed. Histology showed adrenal medullary hyperplasia (AMH). AMH is a rare diagnosis and its incidence is poorly documented in the literature. This is a benign entity which resembles pheochromocytoma (PCC) in both clinical and biochemical manner. AMH is usually bilateral and may occur in isolation or in association with PCC. In fact, some authors consider it to be a precursor to PCC. Thus, these patients need long-term follow-up in view of the risk of development of PCC later.Locally advanced gastric cancer (GC) is often managed by neoadjuvant chemotherapy and surgery; however, pathological complete responses to preoperative systemic treatment are rare. Some GCs are characterised by high-level microsatellite instability (MSI-H) and therefore are potentially sensitive to anti-PD1 (the programmed death 1) therapy. Neoadjuvant immune checkpoint blockade demonstrated promising results in a number of trials involving various categories of patients with cancer; therefore, we considered feasible to offer preoperative nivolumab to a patient with T3N1M0 MSI-H GC. The patient experienced a reduction of the tumour size and the analysis of surgical material revealed complete elimination of tumour cells. MSI-H status deserves to be considered in future trials on patients with GC.Solitary extramedullary plasmacytoma (SEP) of the larynx is a rare haematological malignancy and an infrequent cause of persisting dysphonia. We present the case of a 54-year-old woman with a long-standing history of dysphonia. While clinical examination showed a rather inconspicuous prominent right vestibular fold, an MRI revealed a laryngeal mass with erosion of the thyroid cartilage. A biopsy taken during rigid endoscopy demonstrated plasma cell infiltration with light chain restriction amidst amyloid deposits. After exclusion of systemic involvement, the diagnosis of an SEP of the larynx with secondary amyloidosis was made. The patient received primary radiation therapy. Another biopsy taken 3 months after the end of therapy did not show any signs of ongoing neoplastic plasma cell disease. The patient was therefore considered to be in remission. She is currently receiving regular follow-up and has not shown signs of persistent or progressive disease for the past 18 months.Intraoperative fractures are a rare complication in total knee arthroplasty. Limited literature exists in regard to the incidence, mechanism of injury and management of intraoperative fractures. The authors report a unique case of an 80-year-old man who sustained a medial tibial plateau fracture that occurred intraoperatively during final tibia bone preparation with the use of the Woolley Tibia Punch (Innomed, Savannah, Georgia, USA). The fracture was managed with the addition of 4.5 mm cortical lag screws and the addition of a stemmed tibial implant to bypass the fracture. This is the first reported case in literature that describes an intraoperative medial tibial plateau that occurred through the use of a Woolley Tibia Punch. The authors recommend the consideration of drilling to prepare sclerotic bone for cement penetration rather than a punch in order to minimise the potential for intraoperative fractures that may occur with the use of a punch.The plasma membrane of neurons consists of distinct domains, each of which carries specialized functions and a characteristic set of membrane proteins. While this compartmentalized membrane organization is essential for neuronal functions, it remains controversial how neurons establish these domains on the laterally fluid membrane. Here, using immunostaining, lipid-MS analysis and gene ablation with the CRISPR/Cas9 system, we report that the pancreatic lipase-related protein 2 (PLRP2), a phospholipase A1 (PLA1), is a key organizer of membrane protein localization at the neurite tips of PC12 cells. PLRP2 produced local distribution of 1-oleoyl-2-palmitoyl-PC at these sites through acyl-chain remodeling of membrane phospholipids. The resulting lipid domain assembled the syntaxin 4 (Stx4) protein within itself by selectively interacting with the transmembrane domain of Stx4. The localized Stx4, in turn, facilitated the fusion of transport vesicles that contained the dopamine transporter with the domain of the plasma membrane, which led to the localized distribution of the transporter to that domain. These results revealed the pivotal roles of PLA1, specifically PLRP2, in the formation of functional domains in the plasma membrane of neurons. In addition, our results suggest a mode of membrane organization in which the local acyl-chain remodeling of membrane phospholipids controls the selective localization of membrane proteins by regulating both lipid-protein interactions and the fusion of transport vesicles to the lipid domain.Atherosclerosis is characterized by the pathological accumulation of cholesterol-laden macrophages in the arterial wall. Atherosclerosis is also the main underlying cause of CVDs, and its development is largely driven by elevated plasma cholesterol. Strong epidemiological data find an inverse association between plasma β-carotene with atherosclerosis, and we recently showed that β-carotene oxygenase 1 (BCO1) activity, responsible for β-carotene cleavage to vitamin A, is associated with reduced plasma cholesterol in humans and mice. In this study, we explore whether intact β-carotene or vitamin A affects atherosclerosis progression in the atheroprone LDLR-deficient mice. Compared with control-fed Ldlr-/- mice, β-carotene-supplemented mice showed reduced atherosclerotic lesion size at the level of the aortic root and reduced plasma cholesterol levels.  https://www.selleckchem.com/products/LY2228820.html  These changes were absent in Ldlr-/- /Bco1-/- mice despite accumulating β-carotene in plasma and atherosclerotic lesions. We discarded the implication of myeloid BCO1 in the development of atherosclerosis by performing bone marrow transplant experiments.