Accepted

Fabry disease is an X-linked glycolipid storage disorder caused by mutations in the gene which result in a deficiency in the lysosomal enzyme alpha galactosidase A (AGA). As a result, the glycolipid substrate Gb3 accumulates in critical tissues and organs producing a progressive debilitating disease. In Fabry disease up to 80% of patients experience life-long neuropathic pain that is difficult to treat and greatly affects their quality of life. The molecular mechanisms by which deficiency of AGA leads to neuropathic pain are not well understood, due in part to a lack of models that can be used to study the underlying pathology at the cellular level. Using CRISPR-Cas9 gene editing, we generated two clones with mutations in the gene from a human embryonic stem cell line. Our clonal cell lines maintained normal stem cell morphology and markers for pluripotency, and showed the phenotypic characteristics of Fabry disease including absent AGA activity and intracellular accumulation of Gb3. Mutations in the predicted locations in exon 1 of the gene were confirmed. Using established techniques for dual-SMAD inhibition/WNT activation, we were able to show that our AGA-deficient clones, as well as wild-type controls, could be differentiated to peripheral-type sensory neurons that express pain receptors. This genetically and physiologically relevant human model system offers a new and promising tool for investigating the cellular mechanisms of peripheral neuropathy in Fabry disease and may assist in the development of new therapeutic strategies to help lessen the burden of this disease.

Evidence exists regarding the impact of flourishing in individuals living with chronic pain, but there are currently no reviews which collate the literature on flourishing in adolescents living with chronic pain and their parents. Therefore, the aim of this scoping review was to map and review the current literature, to document how flourishing is defined and understood in the literature, and to identify gaps in the field. Six databases were searched (Web of Science, Medline, Embase, APA PsycNet and the Cochrane Central Register of Controlled Trials). In addition, a limited gray literature search was conducted. The resulting data were collated and reported in relation to the review questions, by examining the included papers to search for the presence of flourishing. Database searches resulted in 7326 papers after duplicate removal, with eight remaining papers being assessed for full-text eligibility. Following full-text screening, a final four papers were included in the review. Within the papers, flourishing was defined in relation to commonalities of benefit finding, enhanced maturity and growth, and social support. Gaps in the literature and directions for future research are considered. This review suggests that there is a dearth of knowledge and research regarding flourishing among adolescents living with chronic pain and their parents, despite aspects of flourishing identified in limited literature. This warrants further investigation.

Cannabis has been proposed as a therapeutic with potential opioid-sparing properties in chronic pain, and its use could theoretically be associated with decreased amounts of opioids used and decreased risk of mortality among individuals prescribed opioids.

Accumulating evidence reveals that music therapy appears to help patients with pain. However, there is a limited understanding of the underlying mechanisms. Several studies indicate that leptin level has a crucial relationship with acute and chronic pain. Herein, we evaluated the effects of music stimulation and the potential roles of adipokines (leptin) in pain behaviors.

Preemptive analgesia may improve postoperative pain management, but the optimal regimen is unclear. This study aimed to compare the effects and adverse events of preemptive analgesia on postoperative pain and opioid consumption.

Oral health is essential to human health. Conditions associated with poor oral health involve all organ systems and many major disease categories including infectious disease, cardiovascular disease, chronic pain, cancer, and mental health. Outcomes are also associated with health equity. Medical education organizations including the Association of American Medical Colleges and National Academy of Medicine recommend that oral health be part of medical education. However, oral health is not traditionally included in many medical school, physician assistant, or nurse practitioner curricula. Several challenges explain this exclusion including lack of time, expertise, and prioritization; we therefore provide suggestions for integrating oral health education into the health professions school curriculum. These recommendations offer guidance for enhancing the oral health curriculum across institutions. We include key organizational and foundational steps, strategies to link oral health with existing content, and approaches to achieve curricular sustainability.

Acute pain among children is common, yet it may be underestimated and undertreated if the pain is not recognized. Assessing and managing pediatric pain can be complicated, and as such, measuring the prevalence of acute pain in children can be challenging. We sought to provide a consolidated review of the available data on the prevalence of commonly occurring acute pain in children in the self-care setting. An extensive literature search was performed to determine the prevalence of acute pain at multiple bodily locations in children aged between 3 months and 18 years. We considered the influence of age, sex, and sociodemographic factors on prevalence estimates. We also sought to identify some of the challenges involved in assessing and managing pediatric pain, thus shedding light on areas where there may be clinical and medical unmet needs. In general, a high prevalence of acute pain in children was detected, particularly headache, menstruation-related pain, and dental and back pain. Older age, female sex, and lower socioeconomic status were associated with increased pain prevalence. Risk factors were identified for all pain types and included psychological issues, stress, and unhealthy lifestyle habits. Owing to the heterogeneity in study populations, the prevalence estimates varied widely; there was also heterogeneity in the pain assessment tools utilized. The paucity of information regarding pain prevalence appears to be out of proportion with the burden of acute pain in children. This could indicate that clinicians may not be equipped with an optimal pain management strategy to guide their practice, especially regarding the use of developmentally appropriate pain assessment tools, without which prevalence data may not be captured. If acute pain is not accurately identified, it cannot be optimally treated. Further investigation is required to determine how the information from prevalence studies translates to the real-world setting.

Pain assessment and management are essential components of paediatric care. Developmentally appropriate pain assessment is an important first step in optimizing pain management. Self-reported pain should be prioritized. Alternatively, developmentally appropriate behavioural tools should be used. Acute pain management and prevention guidelines and strategies that combine physical, psychological, and pharmacological approaches should be accessible in all health care settings. Chronic pain is best managed using combined treatment modalities and counselling, with the primary goal of attaining functional improvement. The planning and implementation of pain management strategies for children should always be personalized and family-centred.

Long-term sequelae after symptomatic SARS-CoV-2 infection may impact well-being, yet existing data primarily focus on discrete symptoms and/or health care use.