Bioplastics: No solution to healthcare's plastic pollution problem.

As Canadian policy-makers recognize the urgency for concerted actions to reduce plastics (e.g., Canada's involvement in the International Plastics Treaty negotiations, Zero Plastic Waste Strategy, and single-use plastics regulations), the healthcare sector must also consider a more sustainable plastics system. In this context, the potential for novel bioplastics to mitigate healthcare's substantial plastic waste problem must be carefully interrogated. Our analysis examines the complexities of bioplastics, highlighting the technical challenges of identifying legitimate sustainable alternatives, and the practical barriers for implementing bioplastics as substitutes for consumable plastics in healthcare. We focus on the Canadian healthcare sector and regulatory landscape with the insights gained being applicable to other sectors and countries. Given the limitations identified, the focus on reducing consumption should remain the priority.

Gut bacteria convert glucocorticoids into progestins in the presence of hydrogen gas.

Recent studies suggest that human-associated bacteria interact with host-produced steroids, but the mechanisms and physiological impact of such interactions remain unclear. Here, we show that the human gut bacteria Gordonibacter pamelaeae and Eggerthella lenta convert abundant biliary corticoids into progestins through 21-dehydroxylation, thereby transforming a class of immuno- and metabo-regulatory steroids into a class of sex hormones and neurosteroids. Using comparative genomics, homologous expression, and heterologous expression, we identify a bacterial gene cluster that performs 21-dehydroxylation. We also uncover an unexpected role for hydrogen gas production by gut commensals in promoting 21-dehydroxylation, suggesting that hydrogen modulates secondary metabolism in the gut. Levels of certain bacterial progestins, including allopregnanolone, better known as brexanolone, an FDA-approved drug for postpartum depression, are substantially increased in feces from pregnant humans. Thus, bacterial conversion of corticoids into progestins may affect host physiology, particularly in the context of pregnancy and women's health.

Context-Specific Stress Causes Compartmentalized SARM1 Activation and Local Degeneration in Cortical Neurons.

Sterile alpha and TIR motif containing 1 (SARM1) is an inducible NADase that localizes to mitochondria throughout neurons and senses metabolic changes that occur after injury. Minimal proteomic changes are observed upon either SARM1 depletion or activation, suggesting that SARM1 does not exert broad effects on neuronal protein homeostasis. However, whether SARM1 activation occurs throughout the neuron in response to injury and cell stress remains largely unknown. Using a semiautomated imaging pipeline and a custom-built deep learning scoring algorithm, we studied degeneration in both mixed-sex mouse primary cortical neurons and male human-induced pluripotent stem cell-derived cortical neurons in response to a number of different stressors. We show that SARM1 activation is differentially restricted to specific neuronal compartments depending on the stressor. Cortical neurons undergo SARM1-dependent axon degeneration after mechanical transection, and SARM1 activation is limited to the axonal compartment distal to the injury site. However, global SARM1 activation following vacor treatment causes both cell body and axon degeneration. Context-specific stressors, such as microtubule dysfunction and mitochondrial stress, induce axonal SARM1 activation leading to SARM1-dependent axon degeneration and SARM1-independent cell body death. Our data reveal that compartment-specific SARM1-mediated death signaling is dependent on the type of injury and cellular stressor.

Correlation of Blomia tropicalis-specific immunoglobulin epsilon profiles with family history of atopy in a Filipino population.

Background: House dust mites are the major source of indoor allergens in the tropical and subtropical regions with Blomia tropicalis (Bt) allergens as one of the leading causative agents of sensitization among patients from the tropics. Despite the clinical importance of Bt in various populations, its allergenicity remains unclear among Filipino allergic patients. Objective: This study determined the sensitization profiles of allergic Filipinos against Bt allergens and its correlation with atopy. Methods: Total immunoglobulin epsilon (IgE) (n = 960), Bt-specific IgE (n = 247), and Blomia tropicalis 5 (Blo t 5)-specific IgE (n = 87) profiles of allergic and nonallergic subjects were measured through enzyme-linked immunosorbent assay (ELISA). Point-biserial correlation coefficient was used to determine the association between Bt-specific IgE levels and selected demographics. Inhibition ELISA was performed to measure the inhibition capacity of recombinant Blo t 5 (rBlo t 5) against Bt allergen extracts. Results: Mean total IgE levels of allergic cases (n = 171) were significantly higher (P < 0.001) compared to the mean IgE levels of nonallergic controls (n = 76). Among allergic subjects, 58% were sensitized to Blo t extract and 80% of which were sensitized to rBlo t 5 allergen. A positive correlation was observed between Bt-specific IgE and family history of atopic disease (P = 0.031). Inhibition assay revealed that 54% mean reactivity of 7 plasma samples was caused by rBlo t 5, validating that rBlo t 5 is a major allergen in Bt. Conclusions: This study has shown the importance of Bt as an allergen source that sensitizes atopic Filipino subjects. Hence, inclusion of Bt allergen extract and rBlo t 5 in the panel for allergy diagnosis and immunotherapy in Filipino populations is strongly recommended.

Reductions of Plastic Microbeads from Personal Care Products in Wastewater Effluents and Lake Waters Following Regulatory Actions.

Plastic microbeads were widely used as exfoliants in personal care products (PCPs; e.g., hand/body washes) in North America, but restrictions were imposed on their use in PCPs in the U.S. (2017) and Canada (2018). We provide the first assessment of whether restrictions are effectively reducing microbeads entering surface waters. We examined their abundance, character, and trends in wastewater treatment plant (WWTP) effluents in Toronto, Canada, from 2016 to 2019, and in adjacent Lake Ontario surface waters (2015 and 2018), encompassing the period before and after the bans. Microbeads isolated from PCPs purchased in 2015 provided a visual morphological key with "irregular" and "spherical" microbead categories. Median concentrations of irregular microbeads, composed of polyethylene plastic, declined by up to 86% in WWTP effluents from 8.4 to 14.3 particles/m3 before to 2.0-2.2 particles/m3 after the bans, while those of spherical microbeads, predominantly synthetic/polyethylene wax, ranged within 0.5-2.3 particles/m3 and did not differ before and after the bans since, as nonplastic, they were not regulated. Similarly, amounts of irregular microbeads declined relative to spherical microbeads in Lake Ontario, indicating that product changes may be influencing observations in lake waters. The results suggest that the Canadian and U.S. restrictions effectively and rapidly reduced plastic microbeads entering waters via WWTPs.

A Review of Current and Pipeline Drugs for Treatment of Melanoma.

Malignant melanoma is the most aggressive form of skin cancer. Standard treatment options include surgery, radiation therapy, systemic chemotherapy, targeted therapy, and immunotherapy. Combining these modalities often yields better responses. Surgery is suitable for localized cases, sometimes involving lymph node dissection and biopsy, to assess the spread of the disease. Radiation therapy may be sometimes used as a standalone treatment or following surgical excision. Systemic chemotherapy, while having low response rates, is utilized as part of combination treatments or when other methods fail. The development of resistance to systemic chemotherapies and associated side effects have prompted further research and clinical trials for novel approaches. In the case of advanced-stage melanoma, a comprehensive approach may be necessary, incorporating targeted therapies and immunotherapies that demonstrate significant antitumor activity. Targeted therapies, including inhibitors targeting BRAF, MEK, c-KIT, and NRAS, are designed to block the specific molecules responsible for tumor growth. These therapies show promise, particularly in patients with corresponding mutations. Combination therapy, including BRAF and MEK inhibitors, has been evidenced to improve progression-free survival; however, concerns about resistance and cutaneous toxicities highlight the need for close monitoring. Immunotherapies, leveraging tumor-infiltrating lymphocytes and CAR T cells, enhance immune responses. Lifileucel, an FDA-approved tumor-infiltrating lymphocyte therapy, has demonstrated improved response rates in advanced-stage melanoma. Ongoing trials continue to explore the efficacy of CAR T-cell therapy for advanced melanoma. Checkpoint inhibitors targeting CTLA-4 and PD-1 have enhanced outcomes. Emerging IL-2 therapies boost dendritic cells, enhancing anticancer immunity. Oncolytic virus therapy, approved for advanced melanoma, augments treatment efficacy in combination approaches. While immunotherapy has significantly advanced melanoma treatment, its success varies, prompting research into new drugs and factors influencing outcomes. This review provides insights into current melanoma treatments and recent therapeutic advances.

Hypoxic transcriptomes predict survival and tumor-infiltrating immune cell composition in cutaneous melanoma.

Hypoxia has established associations with aggressive tumor phenotypes in many cancers. However, it is not currently understood whether tumor hypoxia levels map to distinct immune infiltrates in cutaneous melanoma, potentially unveiling novel therapeutic targets. To this end, we leveraged a previously identified seven-gene hypoxia signature to grade hypoxia levels of 460 cutaneous melanomas obtained from the Broad Institute GDAC Firehose portal. CIBERSORTx ( https://cibersortx.stanford.edu/ ) was employed to calculate the relative abundance of 22 mature human hematopoietic populations. Clinical outcomes and immune cell associations were assessed by computational means. Results indicated that patients with high-hypoxia tumors reported significantly worse overall survival and correlated with greater Breslow depth, validating the in-silico methodology. High-hypoxia tumors demonstrated increased infiltration of activated and resting dendritic cells, resting mast cells, neutrophils, and resting NK cells, but lower infiltration of gamma-delta T cells. These data suggest that high tumor hypoxia correlates with lower survival probability and distinct population differences of several tumor-infiltrating leukocytes in cutaneous melanomas.

Cutaneous Manifestations of Rheumatoid Arthritis: Diagnosis and Treatment.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disorder characterized by inflammatory arthritis and periarticular structural damage. Available evidence suggests that RA results from complex interactions between genetic susceptibility (e.g., HLA-DRB1), environmental factors (e.g., smoking), and immune dysregulation. Alongside joint-related symptoms, individuals with RA may also experience a wide array of skin issues, including the development of nodules, neutrophilic dermatoses, vasculitis, and vasculopathy. Treatment strategies for these manifestations vary but routinely involve corticosteroids, disease-modifying anti-rheumatic drugs, and biologics, with individualized approaches guided by disease severity. In this review, we provide comprehensive insights into the skin-related issues associated with RA, outlining their clinical characteristics and histopathological findings. Our aim is to facilitate early diagnosis and personalized treatment to improve the quality of life of affected individuals.

Avian influenza A viruses exhibit plasticity in sialylglycoconjugate receptor usage in human lung cells.

IMPORTANCE: It is well known that influenza A viruses (IAV) initiate host cell infection by binding to sialic acid, a sugar molecule present at the ends of various sugar chains called glycoconjugates. These sugar chains can vary in chain length, structure, and composition. However, it remains unknown if IAV strains preferentially bind to sialic acid on specific glycoconjugate type(s) for host cell infection. Here, we utilized CRISPR gene editing to abolish sialic acid on different glycoconjugate types in human lung cells, and evaluated human versus avian IAV infections. Our studies show that both human and avian IAV strains can infect human lung cells by utilizing any of the three major sialic acid-containing glycoconjugate types, specifically N-glycans, O-glycans, and glycolipids. Interestingly, simultaneous elimination of sialic acid on all three major glycoconjugate types in human lung cells dramatically decreased human IAV infection, yet had little effect on avian IAV infection. These studies show that avian IAV strains effectively utilize other less prevalent glycoconjugates for infection, whereas human IAV strains rely on a limited repertoire of glycoconjugate types. The remarkable ability of avian IAV strains to utilize diverse glycoconjugate types may allow for easy transmission into new host species.

Effect of concurrent mitral valve surgery for secondary mitral regurgitation upon mortality after aortic valve replacement or coronary artery bypass surgery.

Objectives: It is uncertain whether concurrent mitral valve repair or replacement for moderate or greater secondary mitral regurgitation at the time of coronary artery bypass graft or aortic valve replacement surgery improves long-term survival. Methods: Patients undergoing coronary artery bypass graft and/or aortic valve replacement surgery with moderate or greater secondary mitral regurgitation were reviewed. The effect of concurrent mitral valve repair or replacement upon long-term mortality was assessed while accounting for patient and operative characteristics and mitral regurgitation severity. Results: Of 1,515 patients, 938 underwent coronary artery bypass graft or aortic valve replacement surgery alone and 577 underwent concurrent mitral valve repair or replacement. Concurrent mitral valve repair or replacement did not alter the risk of postoperative mortality for patients with moderate mitral regurgitation (hazard ratio = 0.93; 0.75-1.17) or more-than-moderate mitral regurgitation (hazard ratio = 1.09; 0.74-1.60) in multivariable regression. Patients with more-than-moderate mitral regurgitation undergoing coronary artery bypass graft-only surgery had a survival advantage from concurrent mitral valve repair or replacement in the first two postoperative years (P = 0.028) that did not persist beyond that time. Patients who underwent concurrent mitral valve repair or replacement had a higher rate of later mitral valve operation or reoperation over the five subsequent years (1.9% vs. 0.2%; P = 0.0014) than those who did not. Conclusions: These observations suggest that mitral valve repair or replacement for more-than-moderate mitral regurgitation at the time of coronary artery bypass grafting may be reasonable in a suitably selected coronary artery bypass graft population but not for aortic valve replacement, with or without coronary artery bypass grafting. Our findings are supportive of 2021 European guidelines that severe secondary mitral regurgitation "should" or be "reasonabl[y]" intervened upon at the time of coronary artery bypass grafting but do not support 2020 American guidelines for performing mitral valve repair or replacement concurrent with aortic valve replacement, with or without coronary artery bypass grafting.

Challenges and Opportunities in Building a Global Representative Single-Cell and Spatial Atlas in Cancer.

SUMMARY: Cancer health disparities are complex and a mixture of factors that need to be accounted for in both our planning, implementation, and execution across all researchers, especially in single-cell and spatial technologies, which have a higher burden for adoption in low- and middle-income countries. This commentary tackles the hurdles these technologies face in creating a diverse, representative atlas of cancer and is a call to arms for a strategic plan toward inclusivity across all global populations.