What should constitute a control condition in psychedelic drug trials?

Over the past decade there has been a surge in interest in placebo-controlled trials using non-classical 3,4-methylenedioxymethamphetamine (MDMA) and classical psychedelics such as psilocybin, lysergic acid diethylamide (LSD) and ,-dimethyltryptamine (DMT) to treat neuropsychiatric disorders. However, the success and reliability of these trials depend on the design of the trials, the choice of control conditions, and the ability to blind both participants and researchers. When appropriate control conditions are lacking, it becomes difficult to disentangle placebo and expectation effects from medication effects.

Anterior Cruciate Ligament Reconstruction Basics: Quadriceps Tendon (All-Soft Tissue) Autograft Preparation-Part 2.

Anterior cruciate ligament reconstruction with quadriceps tendon autograft is a reliable graft option that has recently increased in use. Varying harvesting and graft preparation techniques available and improved technology and implant design continue to make quadricep tendon preparation more efficient and reproducible. In this Technical Note, we describe our preferred technique for all-soft tissue quadriceps tendon autograft preparation after harvest for anterior cruciate ligament reconstruction.

Rehabilitation of human hearing with a totally implantable cochlear implant: a feasibility study.

Background: Cochlear implants (CIs) are neuroprosthetic devices which restore hearing in severe-to-profound hearing loss through electrical stimulation of the auditory nerve. Current CIs use an externally worn audio processor. A long-term goal in the field has been to develop a device in which all components are contained within a single implant.

GOLD grade-specific characterization of COPD in the COSYCONET multi-center trial: comparison of semiquantitative MRI and quantitative CT.

Objectives: We hypothesized that semiquantitative visual scoring of lung MRI is suitable for GOLD-grade specific characterization of parenchymal and airway disease in COPD and that MRI scores correlate with quantitative CT (QCT) and pulmonary function test (PFT) parameters.

Methods: Five hundred ninety-eight subjects from the COSYCONET study (median age = 67 (60-72)) at risk for COPD or with GOLD1-4 underwent PFT, same-day paired inspiratory/expiratory CT, and structural and contrast-enhanced MRI. QCT assessed total lung volume (TLV), emphysema, and air trapping by parametric response mapping (PRM, PRM) and airway disease by wall percentage (WP).

The Role of [F]F-FDG PET/CT for Predicting Histology and Prognosis in Patients with Thymic Lesions.

Objectives: To investigate whether 18F-fluorodeoxyglucose positron emission tomography-computed tomography ([F]F-FDG PET/CT) metabolic parameters were associated with histology and to assess their prognostic role in patients with thymic lesions.

Patients And Methods: In total, 116 patients (49/67 M/F; mean age 59.5 years) who underwent preoperative [F]F-FDG PET/CT and thymectomy from 2012 to 2022 were retrospectively analyzed.

Osteoporosis in Older Men: Informing Patient Management and Improving Health-Related Outcomes.

Osteoporosis has been usually considered a female disease, generally causing more fracture risk and complications in adult and older women compared to older men. While vertebral fractures occur in a small proportion of men during middle age, men generally fracture about 10 years later than women, with significant increases in fracture risk after about age 75. Independent of age, men experiencing fragility fractures have a higher risk of life-threatening events compared to women, but the risk of secondary fragility fracture overlaps between men and women.

Neoadjuvant anti-PD-1 alone or in combination with anti-TIGIT or an oncolytic virus in resectable stage IIIB-D melanoma: a phase 1/2 trial.

Neoadjuvant immunotherapies have shown antitumor activity in melanoma. Substudy 02C of the global, rolling-arm, phase 1/2, adaptive-design KEYMAKER-U02 trial is evaluating neoadjuvant pembrolizumab (anti-PD-1) alone or in combination, followed by adjuvant pembrolizumab, for stage IIIB-D melanoma. Here we report results from the first three arms: pembrolizumab plus vibostolimab (anti-TIGIT), pembrolizumab plus gebasaxturev (coxsackievirus A21) and pembrolizumab monotherapy.

Intracerebroventricular anaerobic dopamine in Parkinson's disease with L-dopa-related complications: a phase 1/2 randomized-controlled trial.

Continuous compensation for cerebral dopamine deficiency represents an ideal treatment for Parkinson's disease. Dopamine does not cross the digestive and blood-brain barriers and is rapidly oxidized. The new concept is the intracerebroventricular administration of anaerobic dopamine (A-dopamine) using an abdominal pump connected to a subcutaneous catheter implanted in the third ventricle, near the striatum.

Xalnesiran with or without an Immunomodulator in Chronic Hepatitis B.

Background: Xalnesiran, a small interfering RNA molecule that targets a conserved region of the hepatitis B virus (HBV) genome and silences multiple HBV transcripts, may have efficacy, with or without an immunomodulator, in patients with chronic HBV infection.

Methods: We conducted a phase 2, multicenter, randomized, controlled, adaptive, open-label platform trial that included the evaluation of 48 weeks of treatment with xalnesiran at a dose of 100 mg (group 1), xalnesiran at a dose of 200 mg (group 2), xalnesiran at a dose of 200 mg plus 150 mg of ruzotolimod (group 3), xalnesiran at a dose of 200 mg plus 180 μg of pegylated interferon alfa-2a (group 4), or a nucleoside or nucleotide analogue (NA) alone (group 5) in participants with chronic HBV infection who had virologic suppression with NA therapy. The primary efficacy end point was hepatitis B surface antigen (HBsAg) loss (HBsAg level, <0.

Activity of the mammalian DNA transposon piggyBat from Myotis lucifugus is restricted by its own transposon ends.

Members of the piggyBac superfamily of DNA transposons are widely distributed in host genomes ranging from insects to mammals. The human genome has retained five piggyBac-derived genes as domesticated elements although they are no longer mobile. Here, we have investigated the transposition properties of piggyBat from Myotis lucifugus, the only known active mammalian DNA transposon, and show that its low activity in human cells is due to subterminal inhibitory DNA sequences.

North Pontic crossroads: Mobility in Ukraine from the Bronze Age to the early modern period.

The North Pontic region, which encompasses present-day Ukraine, was a crossroads of migration, connecting the vast Eurasian Steppe with Central Europe. We generated shotgun-sequenced genomic data for 91 individuals dating from around 7000 BCE to 1800 CE to study migration and mobility history in the region, with a particular focus on historically attested migrating groups during the Iron Age and the medieval period. We infer a high degree of temporal heterogeneity in ancestry, with fluctuating genetic affinities to different present-day Eurasian groups.

How to Use Imaging: Complex Cases of Atherosclerosis, Myocardial Inflammation, and Cardiomyopathy in Cardio-Oncology.

It is well understood that cancer therapies including chemotherapy, tyrosine kinase inhibitors, immune checkpoint inhibitors, and radiation can increase the risk of cardiovascular disease in patients with cancer. This can manifest as a multitude of pathologies including left ventricular dysfunction, myocarditis, cardiomyopathy, accelerated atherosclerosis, and coronary vasospasm. Multimodal cardiac imaging plays a critical role in diagnosing such pathologies by relying on noninvasive tools including echocardiograms, cardiac magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, and coronary computed tomography angiography.

A Global Collaborative Comparison of SARS-CoV-2 Antigenicity Across 15 Laboratories.

Setting up a global SARS-CoV-2 surveillance system requires an understanding of how virus isolation and propagation practices, use of animal or human sera, and different neutralisation assay platforms influence assessment of SARS-CoV-2 antigenicity. In this study, with the contribution of 15 independent laboratories across all WHO regions, we carried out a controlled analysis of neutralisation assay platforms using the first WHO International Standard for antibodies to SARS-CoV-2 variants of concern (source: NIBSC). Live virus isolates (source: WHO BioHub or individual labs) or spike plasmids (individual labs) for pseudovirus production were used to perform neutralisation assays using the same serum panels.

Plant Cell Culture-Derived Saponin Adjuvant Enhances Immune Response Against a Stabilized Human Metapneumovirus Pre-Fusion Vaccine Candidate.

Unlabelled: Human metapneumovirus (HMPV) is a significant respiratory pathogen, particularly in vulnerable populations.

Background: No vaccine for the prevention of HMPV is currently licensed, although several subunit vaccines are in development. Saponin-based adjuvant systems (AS), including QS-21, have transformed the field of subunit vaccines by dramatically increasing their potency and efficacy, leading to the development of several licensed vaccines.

Addressing Barriers Newcomer Families Face When Obtaining Routine Childhood Vaccines in Alberta, Canada.

: As the newcomer population in Canada continues to grow, we aimed to collaborate with newcomer families arriving in an urban center in Alberta, Canada to identify strategies to overcome identified barriers newcomers face in obtaining routine childhood vaccines (RCVs). : We recruited newcomers living in Calgary, Alberta to participate in a workshop utilizing the Nominal Group Technique (NGT) to develop solutions addressing barriers to obtaining RCVs. Ranking exercises helped identify the top-proposed interventions based on perceived impact and feasibility for implementation.

Unveiling the Potential of C Factor Applied to Pilot Bioavailability/Bioequivalence Studies-A Case Study with Pazopanib Drug Products.

When companies are uncertain about the potential of a new formulation to be bioequivalent to a Reference product, it is common practice to carry out downsized pilot studies as a gatekeeping in vivo strategy to decide whether to move forward or not with a full-size pivotal study. However, due to the small study size, these studies are inarguably more sensitive to variability. To address and mitigate the uncertainty of the conclusions of pilot studies concerning the maximum observed concentration (C), the factor was proposed as an alternative approach to the average bioequivalence statistical methodology.

Clonal Integration Promotes the Photosynthesis of Clonal Plant Under Heterogeneous Pb and/or Pyrene Stress.

Clonal plants can support the growth of their ramets in heterogeneous environments through clonal integration between the ramets. However, the role of clonal integration in modulating ramet photosynthesis under toxic stress, especially combined stress, is unclear. This study examines the impact of clonal integration on under three heterogeneous stresses (Pb, pyrene, and Pb+Pyrene) with two stolon connection conditions (connected and disconnected).

Dietary RNA from Torula Yeast Prevents Capillary Regression in Atrophied Skeletal Muscle in Rats.

Chronic neuromuscular inactivity induces capillary regression within skeletal muscle. The objective of this study was to investigate the potential effects of dietary nucleic acids in counteracting the capillary reduction linked to chronic neuromuscular inactivity in the soleus muscle. The study utilized four distinct groups of female Wistar rats: a control group (CON), a hindlimb-unloading group (HU), an HU group supplemented with DNA (HU + DNA), and an HU group supplemented with RNA (HU + RNA).

Scoping Review of Climate Change Adaptation Interventions for Health: Implications for Policy and Practice.

Climate change is among the greatest threats to health in the 21st century, requiring the urgent scaling-up of adaptation interventions. We aim to summarise adaptation interventions that were funded by the Belmont Forum and the European Union, the largest global funders of climate change and health research. A systematic search was conducted (updated February 2023) to identify articles on adaptation interventions for health within this funding network.

Comparison of Bone Marrow Biopsy and Flow Cytometry in Demonstrating Bone Marrow Metastasis of Neuroblastoma.

Objective: This study aimed to compare bone marrow aspirate (BMA) multicolor flow cytometry (MFC) analysis and bone marrow biopsy (BMB) in detecting bone marrow (BM) involvement in children with neuroblastoma (NB) at diagnosis and during follow-up.

Materials And Methods: A total of 132 BM samples from 39 patients (M/F ratio: 19/20; median age: 38 months) with neuroblastoma were simultaneously obtained for evaluation. The samples were investigated for BM involvement using BMB and MFC.

Understanding the Patient Experience with Twice-Nightly Sodium Oxybate Therapy for Narcolepsy: A Social Listening Experiment.

Background/objectives: Narcolepsy is a chronic neurologic disorder associated with substantial challenges that affect the social, emotional, and financial quality-of-life domains. A social listening analysis and structured survey were conducted to better understand the candid perspective of people with narcolepsy (PWN) and their experience with twice-nightly sodium oxybate (SXB).

Methods: To characterize conversations and experiences in narcolepsy communities where SXB was mentioned, a social media analysis was conducted from August 2011 to October 2022.

Mucosal-adapted bacteriophages as a preventive strategy for a lethal Pseudomonas aeruginosa challenge in mice.

Pseudomonas aeruginosa is an emergent threat due to the antimicrobial resistance crisis. Bacteriophages (phages) are promising agents for phage therapy approaches against P. aeruginosa.

Prognostic factors for overall survival in elderly patients with glioblastoma: Analysis of the pooled NOA-08 and Nordic trials with the CCTG-EORTC (CE.6) trial.

Background: The majority of patients diagnosed with glioblastoma are >60 years. Three randomized trials addressed the roles of radiotherapy (RT) and temozolomide (TMZ) for elderly patients. NORDIC and NOA-08 compared RT versus TMZ, while CE.

With Proper Surgical Indications, Sex-Based Differences in Pathology Do Not Impact Hip Arthroscopy Outcomes or Complications: A Systematic Review.

Purpose: To identify sex-based differences in pathology, outcomes, and complications after hip arthroscopy for femoroacetabular impingement (FAI), and to compare patient-reported outcomes (PRO) scores between male and female patients.

Methods: The PubMed and MEDLINE databases were searched in September 2024, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included studies had data stratified by sex, minimum 2-year PRO scores for hip arthroscopy in the setting of FAI and labral pathology, and a 2014 or later publication date.

Clinicogenomic landscape of pancreatic adenocarcinoma identifies KRAS mutant dosage as prognostic of overall survival.

Nearly all pancreatic adenocarcinomas (PDAC) are genomically characterized by KRAS exon 2 mutations. Most patients with PDAC present with advanced disease and are treated with cytotoxic therapy. Genomic biomarkers prognostic of disease outcomes have been challenging to identify.