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.

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 fit-for-purpose categorization scheme for microplastic morphologies.

Microplastic categorization schemes are diverse, thereby posing challenges for cross-study comparisons. Further, categorization schemes are not necessarily aligned with and, thus, useful for applications such as source reduction initiatives. To address these challenges, we propose a hierarchical categorization approach that is "fit for purpose" to enable the use of a scheme that is tailored to the study's purpose and contains categories, which, if adopted, would facilitate interstudy comparison. The hierarchical categorization scheme is flexible to support various study purposes (e.g., to support regulation and toxicity assessment) and it aims to improve the consistency and comparability of microplastics categorization. Categorization is primarily based on morphology, supplemented by other identification methods as needed (e.g., spectroscopy). The use of the scheme was illustrated through a literature review aimed at critically evaluating the categories used for reporting microplastic morphologies in North American freshwater environments. Categorization and grouping schemes for microplastic particles were highly variable, with up to 19 different categories used across 68 studies, and nomenclature was inconsistent across particle morphologies. Our review demonstrates the necessity for a "fit for purpose" categorization scheme to guide the information needs of scientists and decision-makers for various research and regulatory objectives across global, regional, and local scales. Integr Environ Assess Manag 2023;19:422-435. © 2022 SETAC.

Aerosolized aqueous dust extracts collected near a drying lake trigger acute neutrophilic pulmonary inflammation reminiscent of microbial innate immune ligands.

BACKGROUND: A high incidence of asthma is prevalent among residents near the Salton Sea, a large inland terminal lake in southern California. This arid region has high levels of ambient particulate matter (PM); yet while high PM levels are often associated with asthma in many environments, it is possible that the rapidly retreating lake, and exposed playa or lakebed, may contribute components with a specific role in promoting asthma symptoms. OBJECTIVES: Our hypothesis is that asthma may be higher in residents closest to the Salton Sea due to chronic exposures to playa dust. Playa emissions may be concentrating dissolved material from the lake, with microbial components capable of inducing pulmonary innate immune responses. To test this hypothesis, we used a mouse model of aerosol exposures to assess the effects of playa dust. METHODS: From dust collected around the Salton Sea region, aqueous extracts were used to generate aerosols, which were injected into an environmental chamber for mouse exposure studies. We compared the effects of exposure to Salton Sea aerosols, as well as to known immunostimulatory reference materials. Acute 48-h and chronic 7-day exposures were compared, with lungs analyzed for inflammatory cell recruitment and gene expression. RESULTS: Dust from sites nearest to the Salton Sea triggered lung neutrophil inflammation that was stronger at 48-h but reduced at 7-days. This acute inflammatory profile and kinetics resembled the response to innate immune ligands LTA and LPS while distinct from the classic allergic response to Alternaria. CONCLUSION: Lung inflammatory responses to Salton Sea dusts are similar to acute innate immune responses, raising the possibility that microbial components are entrained in the dust, promoting inflammation. This effect highlights the health risks at drying terminal lakes from inflammatory components in dust emissions from exposed lakebed.

CD9 blockade suppresses disease progression of high-risk pediatric B-cell precursor acute lymphoblastic leukemia and enhances chemosensitivity.

CD9 has been implicated in cancer progression but its prognostic relevance and therapeutic potential in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) are largely unknown. In a cohort of pediatric BCP-ALL patients, we found that CD9+ cases had a significantly lower 5-year relapse-free survival rate than CD9- cases. Multivariate analysis demonstrated that CD9 positivity independently predicted inferior survival outcomes, and could be applied with established prognostic features, including prednisone response and cytogenetic status, to refine patient stratification. Administration of CD9 antibody substantially suppressed disease progression in NOD/SCID mice xenografted with CD9+ cell lines and primary leukemic blasts from patients with high-risk and refractory BCP-ALL, without compromising hematopoietic stem cell engraftment. Combination of anti-CD9 with conventional chemotherapy further reduced leukemic burden and prolonged animal survival. Mechanistically, CD9 blockade inhibited leukemic cell proliferation, induced G0/G1 cell cycle arrest, activated p38, and enhanced chemotherapeutic agent-induced apoptosis. Further, CD9 physically interacted with integrin very late antigen-4, regulated affinity to vascular cell adhesion molecule-1, and was involved in leukemia-stroma interaction. Collectively, our study established CD9 as a new prognostic marker, validated the preclinical efficacy of CD9 antibody, and laid the foundation for clinical development of CD9-targeted therapy for high-risk and refractory pediatric BCP-ALL.

Do we need another symptom score for childhood eczema?

AIM: It is important to objectively measure the severity of atopic dermatitis (AD). This study aims to investigate correlations among various clinical severity scores and determine how a severity score based on symptoms alone performs. METHODS: A Chinese-translated symptom score based on Patient-Oriented Eczema Measure (POEM, a short-term subjective-symptom score), Scoring Atopic Dermatitis (SCORAD, a short-term subjective-symptom and objective-sign score), Nottingham Eczema Severity Score (NESS, a long-term subjective symptoms + objective signs), Children Dermatology Life Quality Index (CDLQI, a short-term subjective-symptom score), skin hydration (SH) and transepidermal water loss (TEWL) were compared and Spearman's rho correlations was evaluated. RESULTS: 126 sets of clinical scores from eczema patients (mean age: 11.4 ± 5.6 years; 34.7% male) were evaluated. The modified-POEM, objective SCORAD, NESS and CDLQI correlated well with each other. All round, best correlations were obtained with POEM: Objective SCORAD (rho = 0.7, p < 0.001), NESS (rho = 0.69, p < 0.001), SCORAD symptom of itch (rho = 0.75, p < 0.01), SCORAD symptom of sleep loss (rho = 0.64, p < 0.01), CDLQI (rho = 0.77, p < 0.001) and SH (rho= -0.043, p < 0.05). Linear stepwise-backward regression demonstrated that POEM was independently associated with CDLQI parameters of pruritus (B: 2.16; p = 0.018), activities (B: 1.80; p = 0.009), sleep disturbance (B: 2.78; p < 0.001) and NESS parameter of sleep disturbance (B: 1.02; p = 0.003). CONCLUSION: Clinical scores for acute, chronic, subjective symptoms and objective signs correlated well with each other. The symptom measures by modified POEM is easy to perform by parents or patients and correlated better with most other clinical scores, making it an all-round ideal symptom-based severity score for research.

Testing the Actions of a Multi-action Emollient: Patient's Acceptability Determines Product Efficacy.

AIM: Eczema or Atopic Dermatitis (AD) is associated with itch, sleep disturbance, impaired life quality, reduced skin hydration, impaired epidermal barrier function and colonization by Staphylococcus aureus (SA). We investigated an emollient with claimed multi-actions on barrier repair, antihistaminergic and antimicrobial effects. METHODS: Consecutive AD patients were recruited. Swabs and cultures from eczematous areas, disease severity (SCOring Atopic Dermatitis score: SCORAD), quality-of-life (Children Dermatology Life Quality Index, CDLQI), Skin Hydration (SH), and Transepidermal Water Loss (TEWL) were obtained before and 4-week following usage of the emollient. Global or General Acceptability of Treatment (GAT) was obtained (as very good, good, fair or poor). RESULTS: 30 AD patients were recruited. 73% reported "very good" or "good", whereas 27% reported "fair" or "poor" GAT of the emollient. Following the use of the multi-action emollient, area affected, disease intensity and severity significantly improved, especially in the very good/good group (p=0.006-0.035). There was no significant improvement of itch or sleep scores, quality of life, SH, TEWL, S. aureus colonization status, or use of topical treatments. When compared with the historical data of another product, there was no statistical difference between the two creams. CONCLUSION: The emollient is acceptable in nearly three-quarter of AD patients. Patients that accept the moisturizer have less area affected, disease intensity and severity than the non-accepting counterparts following its usage. Despite claim for multi-action, there were no appreciable quality-oflife, anti-itch, skin barrier, and anti-microbial effects.

Emollient Acceptability in Childhood Atopic Dermatitis: Not All Emollients are Equal.

BACKGROUND: Eczema or Atopic Dermatitis (AD) is a common chronic relapsing skin disease associated with impaired quality of life. Regular usage of moisturizer/emollient is the mainstay of management but acceptability of emollient is often suboptimal. We investigated if emollient acceptability is influenced by various clinical factors in AD. METHODS: A survey on frequency of emollient usage, brands, clinical factors including disease severity (Nottingham Eczema Severity Score, NESS), quality of life (Children Dermatology Life Quality Index, CDLQI), Transpidermal Water Loss (TEWL), and Skin Hydration (SH) was performed. Acceptability was classified as very good, good, fair or poor. RESULTS: We evaluated 128 AD patients. NESS correlated with CDLQI and the treatment domain of CDLQI. Emollient usage is elementary for AD treatment. 89.1% of patients reported that doctor's recommendation was the major source of advice when choosing an emollient. Aqueous cream (AQ) and petroleum-derived products were among the commonly used emollients. More aqueous cream users reported fair/poor acceptability (p=0.017) and lower SH (p<0.05). Linear regression showed that patients who thought their emollient as fair or poor were currently using AQ (p=0.003), their emollient not recommended by a doctor (p=0.035), with more severe disease (p=0.04), and had lower emollient usage in winter (p=0.05). CONCLUSION: Physicians play a pivotal role in assisting patients to select an emollient that they will accept and use consistently. The studied emollients are generally acceptable by over 80% patients. However, aqueous cream is least acceptable by patients, making it the least favorable emollient to recommend to patients.

Regulation of Circulating Hematopoietic Stem/Progenitor Cells in Preterm Infants with Septicemia.

Preterm infants are at high risk of developing severe sepsis. Circulating hematopoietic stem and progenitor cells (HSPCs; CD45+CD34+) have been suggested to play a vital role in the host immunological defense against invading pathogens. The objectives were to investigate the regulation of circulating HSPCs in preterm infants during infection episodes, and to assess the relationship of CD45+CD34+ cells with immunological mediators and differential leukocyte populations. First, we conducted a cross-sectional case-control study comparing these parameters among infected infants (n = 23), gestational and postnatal age-matched noninfected infants (n = 46), and "healthy" control (CTL) infants (n = 12). Second, we investigated the longitudinal change of CD45+CD34+ cell concentrations in infected infants before, during, and after an infection episode, and compared them with the other two groups. Our cross-sectional results showed that CD45+CD34+ cell count and percentage were significantly reduced in infected infants during systemic infection, compared with the noninfected or CTL infants. There were significant positive correlation between levels of CD45+CD34+ cells and lymphocytes or monocytes, and significant negative correlation between CD45+CD34+ cells and neutrophils or interleukin (IL)-6 in infected infants. Longitudinal analysis showed that changes of CD45+CD34+ cells at the onset of sepsis relative to levels 1 week prior and 1 week postsepsis in infected infants were significantly different from those changes in the corresponding time points for the other two groups. Our findings suggested that circulating HSPCs were dynamically regulated during septicemia and could play an important role in the defense mechanism, plausibly contributing to replenishment of leukocytes during sepsis in preterm infants.

Dysregulated expression of arginine metabolic enzymes in human intestinal tissues of necrotizing enterocolitis and response of CaCO2 cells to bacterial components.

The small intestine is the exclusive site of arginine synthesis in neonates. Low levels of circulating arginine have been associated with the occurrence of necrotizing enterocolitis (NEC) but the mechanism of arginine dysregulation has not been fully elucidated. We aimed to investigate (i) expressional changes of arginine synthesizing and catabolic enzymes in human intestinal tissues of NEC, spontaneous intestinal perforation (SIP) and noninflammatory surgical conditions (Surg-CTL) and to investigate the (ii) mechanisms of arginine dysregulation and enterocyte proliferation upon stimulation by bacterial components, arginine depletion, ARG1 overexpression and nitric oxide (NO) supplementation. Our results showed that expressions of arginine synthesizing enzymes ALDH18A1, ASL, ASS1, CPS1, GLS, OAT and PRODH were significantly decreased in NEC compared with Surg-CTL or SIP tissues. Catabolic enzyme ARG1 was increased (>100-fold) in NEC tissues and histologically demonstrated to be expressed by infiltrating neutrophils. No change in arginine metabolic enzymes was observed between SIP and Surg-CTL tissues. In CaCO2 cells, arginine metabolic enzymes were differentially dysregulated by lipopolysaccharide or lipoteichoic acid. Depletion of arginine reduced cell proliferation and this phenomenon could be partially rescued by NO. Overexpression of ARG1 also reduced enterocyte proliferation. We provided the first expressional profile of arginine metabolic enzymes at the tissue level of NEC. Our findings suggested that arginine homeostasis was severely disturbed and could be triggered by inflammatory responses of enterocytes and infiltrating neutrophils as well as bacterial components. Such reactions could reduce arginine and NO, resulting in mucosal damage. The benefit of arginine supplementation for NEC prophylaxis merits further clinical evaluation.

Kinetics of signaling-DNA-aptamer-ATP binding.

DNA aptamers are molecular biosensors consisting of single functionalized DNA molecules, which can bind to specific targets or complementary DNA sequences. The binding kinetics of DNA aptamers is studied by fluorescence quenching at 23 degrees C . A kinetic model for the binding reaction of DNA aptamer, antisense DNA, and ATP target is developed to describe experimental observations. The approach leads to a simple procedure to deduce relevant kinetic reactions and their rate constants. A comparison between theory and experiments indicates that the previously established bimolecular DNA-ATP binding does not provide a complete description of the experimental data. Side reactions such as trimolecular complexation are proposed. Rate constants of the model are determined by comparing the model predictions and experiments. Good agreements between the model and experiments have been obtained. Possible blocking reactions by the misfolded DNA aptamer are also discussed.