Quality risk management and data integrity in R&D laboratories supporting CMC lifecycle of biological products.

The development of pharmaceutical products is the critical bridge that moves a potential new medicine from academic discovery to applied treatment of patients. It translates an idea for a new drug to bench-level research on how it can be manufactured, formulated, characterized and controlled for use in non-clinical and early clinical trials. From pre-clinical R&D discovery work through the commercial launch, substantial R&D CMC data is generated to develop and optimize cGMP manufacturing and testing operations, while also supporting product comparability, elucidating product / impurity structures, assessing critical quality attributes, developing the drug delivery mode, and developing the product formulation for long-term stability.

Experimental viral spillover across 25 million year gap in Rodentia reveals limited viral transmission and purifying selection of a picornavirus.

When a virus crosses from one host species to another, the consequences can be devastating. However, animal models to empirically evaluate cross-species transmission can fail to recapitulate natural transmission routes, physiologically relevant doses of pathogens, and population structures of naturally circulating viruses. Here, we present a new model of cross-species transmission where deer mice () are exposed to the natural virome of pet store mice ().

Tropism for ciliated cells is the dominant driver of influenza viral burst size in the human airway.

Influenza viruses pose a significant burden on global human health. Influenza has a broad cellular tropism in the airway, but how infection of different epithelial cell types impacts replication kinetics and burden in the airways is not fully understood. Using primary human airway cultures, which recapitulate the diverse epithelial cell landscape of the human airways, we investigated the impact of cell type composition on virus tropism and replication kinetics.

High-throughput investigation of genetic design constraints in domesticated Influenza A Virus for transient gene delivery.

Replication-incompetent single cycle infectious Influenza A Virus (sciIAV) has demonstrated utility as a research and vaccination platform. Protein-based therapeutics are increasingly attractive due to their high selectivity and potent efficacy but still suffer from low bioavailability and high manufacturing cost. Transient RNA-mediated delivery is a safe alternative that allows for expression of protein-based therapeutics within the target cells or tissues but is limited by delivery efficiency.

Recent innovations in long-term care coverage and financing: a rapid scoping review.

Objectives: To identify, chart and analyse the literature on recent initiatives to improve long-term care (LTC) coverage, financial protection and financial sustainability for persons aged 60 and older.

Design: Rapid scoping review.

Data Sources: Four databases and four sources of grey literature were searched for reports published between 2017 and 2022.

Comparison of mouse models of microbial experience reveals differences in microbial diversity and response to vaccination.

Specific pathogen-free (SPF) laboratory mice dominate preclinical studies for immunology and vaccinology. Unfortunately, SPF mice often fail to accurately model human responses to vaccination and other immunological perturbations. Several groups have taken different approaches to introduce additional microbial experience to SPF mice to better model human immune experience.

A Retrospective Analysis of Intravenous Insulin versus Insulin and Nebulized Albuterol for the Treatment of Hyperkalemia in the Emergency Department.

There is limited literature evaluating the use of nebulized albuterol in the management of hyperkalemia. The objective was to evaluate the efficacy of insulin alone compared with the addition of nebulized albuterol for the treatment of hyperkalemia. This is a retrospective, single-center evaluation of adult patients with hyperkalemia attending the Emergency Department of a large urban academic medical center.

The relationships among nature connectedness, climate anxiety, climate action, climate knowledge, and mental health.

Introduction: Climate change is a source of global concern that has both direct and general impacts on mental health. A recent study conducted following severe bushfires in Australia demonstrated relationships among nature connectedness, climate action, climate worry, and mental health; for example, nature connectedness was associated with climate worry, which in turn was associated with psychological distress.

Methods: The present study sought to replicate those findings while building on them in two important ways: on those findings in two ways: first, test similar relationships in a different geographical context that has been mostly spared from direct impacts by acute climate events; second, we take into consideration an additional factor, climate knowledge, which has been linked to relevant factors such as climate anxiety.

Sleep deprivation, sleep fragmentation, and social jet lag increase temperature preference in .

Despite the fact that sleep deprivation substantially affects the way animals regulate their body temperature, the specific mechanisms behind this phenomenon are not well understood. In both mammals and flies, neural circuits regulating sleep and thermoregulation overlap, suggesting an interdependence that may be relevant for sleep function. To investigate this relationship further, we exposed flies to 12 h of sleep deprivation, or 48 h of sleep fragmentation and evaluated temperature preference in a thermal gradient.

Preparing Future Surgeons: An Evaluation of Academic Surgeons' Views on Laparoscopic Simulation Training for Medical Students.

Introduction With the development of laparoscopic simulation, medical students are motivated to expand their knowledge and proficiency in basic surgical skills. This study aims to demonstrate their capability and readiness for surgical clerkships and, ultimately, surgical residency. This study's primary objective is to ascertain academic surgeons' perspectives regarding laparoscopic simulation in undergraduate medical education and to determine if early exposure may afford medical students additional opportunities during their surgical clerkships.

Responses of Hermit Thrush (Catharus guttatus) males to conspecific playback with typical and atypical syntactical patterns.

Birdsong exhibits syntactical patterns, wherein singers from a variety of species perform vocal sequences that follow set rules with respect to the order of vocal units (e.g., song types or syllables).

Influence of Graft Type on Lower Extremity Functional Test Performance and Failure Rate After Anterior Cruciate Ligament Reconstruction.

Background: Both autografts and allografts are used to reconstruct the anterior cruciate ligament (ACL) after injury; however, it is unclear whether graft source affects lower extremity functional test performance or failure rate in an active military population.

Objective: To compare lower extremity functional test performance and graft failure rates between ACL grafts [allograft, hamstring, bone-patellar tendon-bone (BTB)].

Study Design: Cross-sectional.

Remember the past, plan for the future: How interactions between risk perception and behavior during the COVID-19 pandemic can inform future Canadian public health policy.

The ongoing COVID-19 pandemic necessitated the implementation of numerous temporary public health policies, including social distancing, masking, and movement limitations. These types of measures require most citizens to follow them to be effective at a population level. This study examined population adherence to emergency public health measures using early data collected in the Spring of 2020, when all Canadian jurisdictions were under relatively strict measures.

Natural rodent model of viral transmission reveals biological features of virus population dynamics.

Emerging viruses threaten global health, but few experimental models can characterize the virus and host factors necessary for within- and cross-species transmission. Here, we leverage a model whereby pet store mice or rats-which harbor natural rodent pathogens-are cohoused with laboratory mice. This "dirty" mouse model offers a platform for studying acute transmission of viruses between and within hosts via natural mechanisms.

EEG Correlates of Middle Eastern Music Improvisations on the Instrument.

The cognitive sciences have witnessed a growing interest in cognitive and neural basis of human creativity. Music improvisations constitute an ideal paradigm to study creativity, but the underlying cognitive processes remain poorly understood. In addition, studies on music improvisations using scales other than the major and minor chords are scarce.

Intra- and Cross-Species Transmission of Astroviruses.

Astroviruses are non-enveloped, single-stranded RNA viruses that infect mammalian and avian species. In humans, astrovirus infections are one of the most common causes of gastroenteritis in children. Infection has also been linked to serious neurological complications, especially in immunocompromised individuals.

Reference Values for the Headache Impact Test-6 Questionnaire.

Objective: To determine reference values for the Headache Impact Test-6 (HIT-6) in a young, physically active cohort and to examine the influence of sex, concussion history, headache history, and competitive sport level on HIT-6 scores.

Design: Cross-sectional.

Setting: United States Service Academy.

Evaluating the mental health and well-being of Canadian healthcare workers during the COVID-19 outbreak.

During the COVID-19 pandemic, healthcare systems have been under extreme levels of stress due to increases in patient distress and patient deaths. While additional research and public health funding initiatives can alleviate these systemic issues, it is also important to consider the ongoing mental health and well-being of professionals working in healthcare. By surveying healthcare workers working in Canada during the COVID-19 pandemic, we found that there was an elevated level of depressive symptomatology in that population.

Factors Associated With Delayed Concussion Reporting by United States Service Academy Cadets.

Context: Approximately half of individuals who sustain a concussion do not immediately report their injuries. Motivators for not reporting include thinking the suspected concussion was not a serious injury and wanting to continue participating in activity. Additionally, military personnel have concerns about how concussions may affect their careers.

Alignment of preferences in the treatment of multiple myeloma - a discrete choice experiment of patient, carer, physician, and nurse preferences.

Background: Multiple Myeloma (MM) is a cancer characterised by the proliferation of malignant plasma cells in the bone marrow. This study examined the treatment preferences of people living with MM compared to the treatment preferences of other groups involved in treatment decision making, including carers, as well as physicians and nurses who treat people living with MM in Australia.

Methods: Data were collected using discrete choice experiments (DCEs) through an online survey.

One-Shot Tagging During Wake and Cueing During Sleep With Spatiotemporal Patterns of Transcranial Electrical Stimulation Can Boost Long-Term Metamemory of Individual Episodes in Humans.

Targeted memory reactivation (TMR) during slow-wave oscillations (SWOs) in sleep has been demonstrated with sensory cues to achieve about 5-12% improvement in post-nap memory performance on simple laboratory tasks. But prior work has not yet addressed the one-shot aspect of episodic memory acquisition, or dealt with the presence of interference from ambient environmental cues in real-world settings. Further, TMR with sensory cues may not be scalable to the multitude of experiences over one's lifetime.

The Influence of Self-Reported Tobacco Use on Baseline Concussion Assessments.

Introduction: Baseline symptom, balance, and neurocognitive scores have become an integral piece of the concussion management process. Factors such as sleep, learning disorders, fitness level, and sex have been linked to differences in performance on baseline assessments; however, it is unclear how tobacco use may affect these scores. The objective of this study was to compare baseline concussion assessment scores between service academy cadets who use and do not use tobacco.

Accuracy and Reliability of Root Crack and Fracture Detection in Teeth Using Magnetic Resonance Imaging.

Introduction: Magnetic resonance imaging (MRI) has the potential to aid in determining the presence and extent of cracks/fractures in teeth because of better contrast without ionizing radiation. The objectives were to develop MRI criteria for root crack/fracture identification and to establish reliability and accuracy in their detection.

Methods: MRI-based criteria for crack/fracture appearance was developed by an MRI physicist and a panel of 6 dentists.

p5RHH nanoparticle-mediated delivery of AXL siRNA inhibits metastasis of ovarian and uterine cancer cells in mouse xenografts.

Ovarian and uterine serous cancers are extremely lethal diseases that often present at an advanced stage. The late-stage diagnosis of these patients results in the metastasis of their cancers throughout the peritoneal cavity leading to death. Improving survival for these patients will require identifying therapeutic targets, strategies to target them, and means to deliver therapies to the tumors.