Conformational dynamics and multi-modal interaction of Paxillin with the Focal Adhesion Targeting Domain.

Paxillin (PXN) and focal adhesion kinase (FAK) are two major components of the focal adhesion complex, a multiprotein structure linking the intracellular cytoskeleton to the cell exterior. PXN interacts directly with the C-terminal targeting domain of FAK (FAT) via its intrinsically disordered N-terminal domain. This interaction is necessary and sufficient for localizing FAK to focal adhesions.

Effectiveness of adductor canal block combined with posterior capsular infiltration on pain and return to walking after total knee arthroplasty: comparative analysis with femoral and popliteal sciatic nerves blocks.

Introduction: Perioperative analgesia after total knee arthroplasty (TKA) reduces morphine consumption and speeds up rehabilitation. The primary objective of this study was to compare the pain experienced by patients with an adductor canal and posterior capsule block with those with a continuous femoral nerve block combined with a popliteal sciatic nerve block. The secondary objectives were to analyze the time to recovery from early walking, length of hospital stay, and block-related complications between the two groups.

SAME day amBulatory c (SAMBA): a multicenter, prospective, randomized clinical trial protocol.

Background: A recent meta-analysis concluded that outpatient appendectomy appears feasible and safe, but there is a lack of high-quality evidence and a randomized trial is needed. The aim of this trial is to demonstrate that outpatient appendectomy is non-inferior to conventional inpatient appendectomy in terms of overall morbi-mortality on the 30th postoperative day (D30).

Methods: SAMBA is a prospective, randomized, controlled, multicenter non-inferiority trial.

Prediction of transfusion risk after total knee arthroplasty: use of a machine learning algorithm.

Introduction: Total knee arthroplasty (TKA) carries a significant hemorrhagic risk, with a non-negligible rate of postoperative transfusions. The blood-sparing strategy has evolved to reduce blood loss after TKA by identifying the patient's risk factors preoperatively. In practice, a blood count is often performed postoperatively but rarely altering the patient's subsequent management.

Solution NMR backbone resonance assignment of the full-length resistance-related calcium-binding protein Sorcin.

Sorcin is a penta-EF hand calcium-binding protein that confers multidrug resistance in cancer cells. It regulates cellular Ca homeostasis by interacting with calcium channels such as Ryanodine receptor 2 and Sarcoplasmic/endoplasmic reticulum Ca-ATPase in a calcium-dependent manner. The crystal structure of the Sorcin has been determined in both calcium-free and calcium-bound states to understand calcium-binding induced conformational change.

Risk prediction of kalaemia disturbance and acute kidney injury after total knee arthroplasty: use of a machine learning algorithm.

Introduction: Total knee arthroplasty (TKA) is a procedure associated with risks of electrolyte and kidney function disorders, which are rare but can lead to serious complications if not correctly identified. A routine check-up is very often carried out to assess the seric ionogram and kidney function after TKA, that rarely requires clinical intervention in the event of a disturbance. The aim of this study was to identify perioperative variables that would lead to the creation of a machine learning model predicting the risk of kalaemia disorders and/or acute kidney injury after total knee arthroplasty.

A single C-terminal residue controls SARS-CoV-2 spike trafficking and incorporation into VLPs.

The spike (S) protein of SARS-CoV-2 is delivered to the virion assembly site in the ER-Golgi Intermediate Compartment (ERGIC) from both the ER and cis-Golgi in infected cells. However, the relevance and modulatory mechanism of this bidirectional trafficking are unclear. Here, using structure-function analyses, we show that S incorporation into virus-like particles (VLP) and VLP fusogenicity are determined by coatomer-dependent S delivery from the cis-Golgi and restricted by S-coatomer dissociation.

Acquired resistance to KRAS G12C small-molecule inhibitors via genetic/nongenetic mechanisms in lung cancer.

Inherent or acquired resistance to sotorasib poses a substantialt challenge for NSCLC treatment. Here, we demonstrate that acquired resistance to sotorasib in isogenic cells correlated with increased expression of integrin β4 (ITGB4), a component of the focal adhesion complex. Silencing ITGB4 in tolerant cells improved sotorasib sensitivity, while overexpressing ITGB4 enhanced tolerance to sotorasib by supporting AKT-mTOR bypass signaling.

Concomitant andexanet alfa and 4 F-PCC for Factor Xa inhibitor associated intracranial hemorrhage.

Andexanet alfa is the only FDA approved drug for acute reversal of life-threatening bleeding associated with oral factor Xa inhibitor agents. The case series investigates clinical outcomes of four patients receiving concomitant Andexanet alfa and Four Factor Prothrombin Concentrate Complex (4 F-PCC) for acute reversal of intracranial hemorrhage. Following administration, effective hemostasis was achieved in two patients (50%) and one patient (25%) experienced an acute ischemic stroke.

Low-Impact Laparoscopy vs Conventional Laparoscopy for Appendectomy: A Prospective Randomized Trial.

Background: Low-impact laparoscopy (LIL), combining low-pressure insufflation and microlaparoscopy, is a surgical technique that is still not widely used and that has never been evaluated for the management of acute appendicitis. The aim of this study is to assess the feasibility of an LIL protocol, to compare postoperative pain, average length of stay, and in-hospital use of analgesics by patients who underwent appendectomy according to a conventional laparoscopy or an LIL protocol.

Study Design: Patients presenting with acute uncomplicated appendicitis who were operated on between January 1, 2021, and July 10, 2022, were included in this double-blind, single-center, prospective study.

Design and characterization of a protein fold switching network.

To better understand how amino acid sequence encodes protein structure, we engineered mutational pathways that connect three common folds (3α, β-grasp, and α/β-plait). The structures of proteins at high sequence-identity intersections in the pathways (nodes) were determined using NMR spectroscopy and analyzed for stability and function. To generate nodes, the amino acid sequence encoding a smaller fold is embedded in the structure of an ~50% larger fold and a new sequence compatible with two sets of native interactions is designed.

Association of the COVID-19 Pandemic With Medical School Diversity Pathway Programs.

Importance: Medical school pathway programs are a strategy to increase the diversity of the physician workforce. The COVID-19 pandemic may have negatively affected pathway programs, further challenging efforts to increase diversity.

Objectives: To describe the changes in medical school pathway programs during the COVID-19 pandemic and identify methods for sustaining and supporting these programs during and after the pandemic.

Analysis of Social Mission Commitment at Dental, Medical, and Nursing Schools in the US.

Importance: The COVID-19 pandemic and calls for racial justice have highlighted the need for schools to promote social mission. Measuring social mission engagement and performance in health professions education may encourage institutional efforts to advance health equity and social justice commitments.

Objective: To describe the current state of social mission commitment within dental, medical, and nursing schools in the US and to examine how social mission performance compares across school types.

Intrinsically disordered proteins: Ensembles at the limits of Anfinsen's dogma.

Intrinsically disordered proteins (IDPs) are proteins that lack rigid 3D structure. Hence, they are often misconceived to present a challenge to Anfinsen's dogma. However, IDPs exist as ensembles that sample a quasi-continuum of rapidly interconverting conformations and, as such, may represent proteins at the extreme limit of the Anfinsen postulate.

Protein conformational dynamics and phenotypic switching.

Intrinsically disordered proteins (IDPs) are proteins that lack rigid 3D structure but exist as conformational ensembles. Because of their structural plasticity, they can interact with multiple partners. The protein interactions between IDPs and their partners form scale-free protein interaction networks (PINs) that facilitate information flow in the cell.

The Scope of Social Mission Content in Health Professions Education Accreditation Standards.

Purpose: Health professions education accreditation standards influence institutional practices and policies and ensure high-quality education that meets the needs of patients and society. Social mission is the contribution of a school in its mission, programs, and the performance of its graduates, faculty, and leadership to advancing health equity and addressing the health disparities of the society in which it exists. This study examined the scope of social mission content in major U.

Peptide-MHC Binding Reveals Conserved Allosteric Sites in MHC Class I- and Class II-Restricted T Cell Receptors (TCRs).

T cells are vital for adaptive immune responses that protect against pathogens and cancers. The T cell receptor (TCR)-CD3 complex comprises a diverse αβ TCR heterodimer in noncovalent association with three invariant CD3 dimers. The TCR is responsible for recognizing antigenic peptides bound to MHC molecules (pMHC), while the CD3 dimers relay activation signals to the T cell.

Alveolar recruitment manoeuvre results in improved pulmonary function in obese patients undergoing bariatric surgery: a randomised trial.

Perioperative ventilation is an important challenge of anaesthesia, especially in obese patients: body mass index is correlated with reduction of the pulmonary volume and they develop significantly more perioperative atelectasis and pulmonary complications. The alveolar recruitment manoeuvre is the most effective technique to reverse atelectasis. However, the clinical benefit on lung function in the perioperative period is not clear.

High Prevalence of Acquired Thrombophilia Without Prognosis Value in Patients With Coronavirus Disease 2019.

Background Recent literature reports a strong thrombotic tendency in patients hospitalized for a coronavirus disease 2019 (COVID-19) infection. This characteristic is unusual and seems specific to COVID-19 infections, especially in their severe form. Viral infections can trigger acquired thrombophilia, which can then lead to thrombotic complications.