Design principles to tailor Hsp104 therapeutics.

The hexameric AAA+ disaggregase, Hsp104, collaborates with Hsp70 and Hsp40 via its autoregulatory middle domain (MD) to solubilize aggregated proteins. However, how ATP- or ADP-specific MD configurations regulate Hsp104 hexamers remains poorly understood. Here, we define an ATP-specific network of interprotomer contacts between nucleotide-binding domain 1 (NBD1) and MD helix L1, which tunes Hsp70 collaboration.

Reconstruction of the historic time course of blood-borne virus contamination of clotting factor concentrates, 1974-1992.

Factor VIII and IX clotting factor concentrates manufactured from pooled plasma have been identified as potent sources of virus infection in persons with hemophilia (PWHs) in the 1970s and 1980s. To investigate the range and diversity of viruses over this period, we analysed 24 clotting factor concentrates for several blood-borne viruses. Nucleic acid was extracted from 14 commercially produced clotting factors and 10 from nonremunerated donors, preserved in lyophilized form (expiry dates: 1974-1992).

Postoperative Neurologic Outcome in Patients Undergoing Resective Surgery for Parietal Lobe Epilepsy: A Systematic Review.

Background And Objectives: Parietal lobe epilepsy (PLE) surgery can be an effective treatment for selected patients with intractable epilepsy but can be associated with the risk of serious neurologic deficits. We performed a systematic review of the literature to obtain a comprehensive summary of the frequency and types of new postoperative neurologic deficits in patients undergoing PLE resective surgery.

Methods: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials for articles published between January 1, 1990, and April 28, 2022.

Design principles to tailor Hsp104 therapeutics.

The hexameric AAA+ disaggregase, Hsp104, collaborates with Hsp70 and Hsp40 via its autoregulatory middle domain (MD) to solubilize aggregated protein conformers. However, how ATP- or ADP-specific MD configurations regulate Hsp104 hexamers remains poorly understood. Here, we define an ATP-specific network of interprotomer contacts between nucleotide-binding domain 1 (NBD1) and MD helix L1, which tunes Hsp70 collaboration.

Midwife continuity of care models versus other models of care for childbearing women.

Background: Midwives are primary providers of care for childbearing women globally and there is a need to establish whether there are differences in effectiveness between midwife continuity of care models and other models of care. This is an update of a review published in 2016.

Objectives: To compare the effects of midwife continuity of care models with other models of care for childbearing women and their infants.

Correction: Bailey et al. Clinical Trials in High-Risk Medulloblastoma: Evolution of the SIOP-Europe HR-MB Trial. 2022, , 374.

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Bevacizumab, Irinotecan, or Topotecan Added to Temozolomide for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON-Neuroblastoma Trial.

Purpose: Outcomes for children with relapsed and refractory high-risk neuroblastoma (RR-HRNB) remain dismal. The BEACON Neuroblastoma trial (EudraCT 2012-000072-42) evaluated three backbone chemotherapy regimens and the addition of the antiangiogenic agent bevacizumab (B).

Materials And Methods: Patients age 1-21 years with RR-HRNB with adequate organ function and performance status were randomly assigned in a 3 × 2 factorial design to temozolomide (T), irinotecan-temozolomide (IT), or topotecan-temozolomide (TTo) with or without B.

Anatomic factors associated with degeneration and fraying of the coracoacromial ligament.

Background: The coracoacromial ligament (CAL) is frequently observed to be damaged during arthroscopy and it is unclear how demographic, anatomic, and radiographic factors are related to CAL degeneration in full-thickness rotator cuff tears.

Methods: A prospective study was conducted of patients at a single institution undergoing shoulder arthroscopy for first-time, full-thickness rotator cuff tears. We evaluated preoperative anteroposterior radiographs to obtain critical shoulder angle, glenoid inclination, acromial index, acromiohumeral distance, lateral acromial angle, and acromial morphology.

Landiolol and Organ Failure in Patients With Septic Shock: The STRESS-L Randomized Clinical Trial.

Importance: Patients with septic shock undergo adrenergic stress, which affects cardiac, immune, inflammatory, and metabolic pathways. β-Blockade may attenuate the adverse effects of catecholamine exposure and has been associated with reduced mortality.

Objectives: To assess the efficacy and safety of landiolol in patients with tachycardia and established septic shock requiring prolonged (>24 hours) vasopressor support.

Investigating Blood Donors With Postdonation Respiratory Tract Symptoms During the Wild-Type, Delta, and Omicron Waves of the Coronavirus Disease 2019 Pandemic in England.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been shown to be detectable in blood from infected individuals. Though RNAemia frequencies are typically low, the presence of potentially infectious virus potentially poses a transmission risk during blood transfusion.

Methods: Archived plasma samples were collected from blood donors who later reported possible SARS-CoV-2 infection with the wild-type strain, Delta variant, or Omicron variant.

biomArker-guided Duration of Antibiotic treatment in hospitalised Patients with suspecTed Sepsis (ADAPT-Sepsis): A protocol for a multicentre randomised controlled trial.

Aim: To describe the protocol for a multi-centre randomised controlled trial to determine whether treatment protocols monitoring daily CRP (C-reactive protein) or PCT (procalcitonin) safely allow a reduction in duration of antibiotic therapy in hospitalised adult patients with sepsis.

Design: Multicentre three-arm randomised controlled trial.

Setting: UK NHS hospitals.

America's Opioid Ecosystem: How Leveraging System Interactions Can Help Curb Addiction, Overdose, and Other Harms.

Opioids play an outsized role in America's drug problems, but they also play a critically important role in medicine. Thus, they deserve special attention. Illegally manufactured opioids (such as fentanyl) are involved in a majority of U.

Postpandemic rebound of adeno-associated virus type 2 (AAV2) infections temporally associated with an outbreak of unexplained severe acute hepatitis in children in the United Kingdom.

Over 1000 cases of unexplained severe acute hepatitis in children have been reported to date worldwide. An association with adeno-associated virus type 2 (AAV2) infection, a human parvovirus, prompted us to investigate the epidemiology of AAV in the United Kingdom. Three hundred pediatric respiratory samples collected before (April 03, 2009-April 03, 2013) and during (April 03, 2022) the COVID-19 pandemic were obtained.

Expelled from the mountain top?

In 1968, Martin Luther King Jr. professed, "We've got some difficult days ahead. But it really doesn't matter with me now, because I've been to the mountaintop….

Complications after operative treatment of high-grade acromioclavicular injuries.

Background: Treatment of Rockwood type III-V acromioclavicular (AC) joint injuries remains controversial. Numerous reconstruction techniques have been proposed. The purpose of this study was to describe the complication profile in a large cohort of patients who underwent surgical management of AC joint separations using a variety of reconstruction strategies.

30-Day Postoperative Complications After Surgical Treatment of Proximal Humerus Fractures: Reverse Total Shoulder Arthroplasty Versus Hemiarthroplasty.

Introduction: The purpose of this study was to evaluate risk factors associated with complications after reverse total shoulder arthroplasty (TSA) and hemiarthroplasty for the treatment of proximal humerus fractures.

Methods: A retrospective review of the American College of Surgeons National Surgical Quality Improvement Program database was conducted. Current Procedural Terminology codes were used to identify patients treated for proximal humerus fracture with reverse TSA or hemiarthroplasty between 2005 and 2018.

Induction of labour for predicted macrosomia: study protocol for the 'Big Baby' randomised controlled trial.

Introduction: Large-for-gestational age (LGA) fetuses have an increased risk of shoulder dystocia. This can lead to adverse neonatal outcomes and death. Early induction of labour in women with a fetus suspected to be macrosomic may mitigate the risk of shoulder dystocia.

Establishing maximal medical improvement following aseptic revision of shoulder arthroplasty.

Background: Shoulder arthroplasty surgery volume continues to increase yearly. As the prevalence of shoulder replacement continues to rise, there will be a growing number of revision surgeries performed for a variety of indications. Understanding patient outcomes and recovery time following these procedures is critical, particularly as it relates to revision surgery, which generally has worse outcomes and longevity than primary arthroplasty.

Research Priorities for Pediatric Intensive Care Nutrition Within the United Kingdom: A National Institute of Health Research James Lind Alliance Priority Setting Partnership.

Objectives: To determine research priorities in PICU nutrition, which represent the shared priorities of patients, parents, carers, and PICU healthcare professionals within the United Kingdom.

Design: A national multiphase priority setting methodology in partnership with the James Lind Alliance delivered over 16 months (June 2020-September 2021). Part 1: a national scoping survey asked respondents to submit their research uncertainties related to PICU nutrition.

Clinical Trials in High-Risk Medulloblastoma: Evolution of the SIOP-Europe HR-MB Trial.

Medulloblastoma patients receive adapted therapies stratified according to their risk-profile. Favourable, standard, and high disease-risk groups are each defined by the status of clinical and pathological risk factors, alongside an evolving repertoire of diagnostic and prognostic biomarkers. Medulloblastoma clinical trials in Europe are coordinated by the International Society for Paediatric Oncology (SIOP-Europe) brain tumour group.

Namilumab or infliximab compared with standard of care in hospitalised patients with COVID-19 (CATALYST): a randomised, multicentre, multi-arm, multistage, open-label, adaptive, phase 2, proof-of-concept trial.

Background: Dysregulated inflammation is associated with poor outcomes in COVID-19. We aimed to assess the efficacy of namilumab (a granulocyte-macrophage colony stimulating factor inhibitor) and infliximab (a tumour necrosis factor inhibitor) in hospitalised patients with COVID-19, to prioritise agents for phase 3 trials.

Methods: In this randomised, multicentre, multi-arm, multistage, parallel-group, open-label, adaptive, phase 2, proof-of-concept trial (CATALYST), we recruited patients (aged ≥16 years) admitted to hospital with COVID-19 pneumonia and C-reactive protein (CRP) concentrations of 40 mg/L or greater, at nine hospitals in the UK.

CATALYST trial protocol: a multicentre, open-label, phase II, multiarm trial for an early and accelerated evaluation of the potential treatments for COVID-19 in hospitalised adults.

Introduction: Severe SARS-CoV-2 infection is associated with a dysregulated immune response. Inflammatory monocytes and macrophages are crucial, promoting injurious, proinflammatory sequelae. Immunomodulation is, therefore, an attractive therapeutic strategy and we sought to test licensed and novel candidate drugs.

Nutrition Intervention for Reduction of Cardiovascular Risk in African Americans Using the 2019 American College of Cardiology/American Heart Association Primary Prevention Guidelines.

Introduction: The 2019 American College of Cardiology/American Heart Association (ACC/AHA) Prevention Guidelines emphasize reduction in dietary sodium, cholesterol, refined carbohydrates, saturated fat and sweetened beverages. We hypothesized that implementing this dietary pattern could reduce cardiovascular risk in a cohort of volunteers in an urban African American (AA) community church, during a 5-week ACC/AHA-styled nutrition intervention, assessed by measuring risk markers and adherence, called HEART-LENS (Helping Everyone Assess Risk Today Lenten Nutrition Study).

Methods: The study population consisted of 53 volunteers who committed to eat only home-delivered non-dairy vegetarian meals (average daily calories 1155, sodium 1285 mg, cholesterol 0 mg; 58% carbohydrate, 17% protein, 25% fat).