Prenatal and Early Life Exposure to Ambient Air Pollutants Is Associated with the Fecal Metabolome in the First Two Years of Life.

Prenatal and early life air pollution exposure has been linked with several adverse health outcomes. However, the mechanisms underlying these relationships are not yet fully understood. Therefore, this study utilizes fecal metabolomics to determine if pre- and postnatal exposure to ambient air pollutants (i.e., PM10, PM2.5, and NO2) is associated with the fecal metabolome in the first 2 years of life in a Latino cohort from Southern California. The aims of this analysis were to estimate associations between (1) prenatal air pollution exposure with fecal metabolic features at 1-month of age, (2) prior month postnatal air pollution exposure with fecal metabolites from 1-month to 2 years of age, and (3) how postnatal air pollution exposure impacts the change over time of fecal metabolites in the first 2 years of life. Prenatal exposure to air pollutants was associated with several Level-1 metabolites, including those involved in vitamin B6 and tyrosine metabolism. Prior month air pollution exposure in the postnatal period was associated with Level-1 metabolites involved in histidine metabolism. Lastly, we found that pre- and postnatal ambient air pollution exposure was associated with changes in metabolic features involved in metabolic pathways including amino acid metabolism, histidine metabolism, and fatty acid metabolism.

First clinical evaluation of the safety and efficacy of tarumase for the debridement of venous leg ulcers.

We report the first clinical evaluation of a new enzymatic wound debridement product containing tarumase in venous leg ulcer patients. As a first-in-human study, this was a prospective, open-label, multi-centre, dose escalation study across five dose cohorts and involving a total of 43 patients treated three times weekly for up to 4 weeks (12 applications). The primary and secondary endpoints of the study were to assess the systemic safety, local tolerability, and early proof of concept both for wound debridement and healing. Results indicated that the tarumase enzyme was well tolerated when applied topically to wounds, with no indications of systemic absorption, no evidence of antibody generation, and no systemic effects on coagulation pathways. Locally, there was no evidence of pain on application, no local itching, no increases in erythema, oedema, exudate or bleeding and only a few treatment emergent adverse events were reported. As the concentration of tarumase was escalated, trends towards faster and improved effectiveness of wound debridement were observed, especially in patients with significant slough at baseline. Trends towards faster rates of healing were also noted based on observations of increased granulation tissue, increased linear healing and reduction in surface area over the 4-week treatment period.

Electronic Consultations in a Community Neurology Practice: A Retrospective Study Informing Best Practice.

Objective: To describe our practice of electronic consultations (e-consults) and assess safety and risk factors for subsequent face-to-face consultations. Patients and Methods: A retrospective cohort study of all e-consults completed in a community neurology practice between May 5, 2018, and June 31, 2019, was completed. Clinical and demographic variables were compared between the successful and unsuccessful (defined by presence of subsequent face-to-face consultation) cohorts. Hazard ratios (HR) were calculated using Cox regression model. Kaplan-Meier probability analysis (with 95% CIs) of subsequent face-to-face consultation was performed. Case examples highlighting potential harm were summarized. Results: In total, 302 e-consults were reviewed. The most frequent referrals were for headache (n=125, 41.4%), dysesthesia (n=40, 13.2%), and abnormal imaging finding (n=27, 8.9%). The most common e-consult questions were for treatment (57.6%) and diagnostic evaluation (48.0%) recommendations. Moreover, 24.8% (n=75) of e-consults were followed by face-to-face consultations, with primary risk factors including female sex (HR, 1.9), referral for headache (HR, 1.7), and final diagnosis of migraine (HR, 2.0) or long-term migraine (HR, 5.0). Potential harm related to delayed diagnosis/treatment was identified in 6 (2.0%) patients with migraine and 4 (1.3%) without migraine presenting to emergency department. Conclusion: Utilization of e-consults may safely improve access to neurologic expertise and prevent the need for some visits, which may have required a face-to-face visit. In patients with chronic migraine, e-consults should be considered short-term and followed by face-to-face consultation as soon as access allows. Neurologists performing e-consults should be able to triage patients to face-to-face consultation, particularly when diagnosis is uncertain or the neurologic examination may help guide appropriate testing.

Collaboration and engagement with decision-makers are needed to reduce evidence complacency in wildlife management.

There exists an extensive, diverse, and robust evidence base to support complex decisions that address the planetary biodiversity crisis. However, it is generally not sought or used by environmental decision-makers, who instead draw on intuition, experience, or opinion to inform important decisions. Thus, there is a need to examine evidence exchange processes in wildlife management to understand the multiple inputs to decisions. Here, we adopt a novel approach, fuzzy cognitive mapping (FCM), to examine perceptions of individuals from Indigenous and Western governments on the reliability of evidence which may influence freshwater fisheries management decisions in British Columbia, Canada. We facilitated four FCM workshops participants representing Indigenous or Western regulatory/governance groups of fisheries managers. Our results show that flows of evidence to decision-makers occur within a relatively closed governance network, constrained to the few well-connected decision-making organizations (i.e., wildlife management agencies) and their close partners. This implies that increased collaboration (i.e., knowledge co-production) and engagement (i.e., knowledge brokerage) with wildlife managers and decision-makers are needed to produce actionable evidence and increase evidence exchange.

Dosage-dependent effects of FGFR2W290R mutation on craniofacial shape and cellular dynamics of the basicranial synchondroses.

Craniosynostosis is a common yet complex birth defect, characterized by premature fusion of the cranial sutures that can be syndromic or nonsyndromic. With over 180 syndromic associations, reaching genetic diagnoses and understanding variations in underlying cellular mechanisms remains a challenge. Variants of FGFR2 are highly associated with craniosynostosis and warrant further investigation. Using the missense mutation FGFR2W290R , an effective mouse model of Crouzon syndrome, craniofacial features were analyzed using geometric morphometrics across developmental time (E10.5-adulthood, n = 665 total). Given the interrelationship between the cranial vault and basicranium in craniosynostosis patients, the basicranium and synchondroses were analyzed in perinates. Embryonic time points showed minimal significant shape differences. However, hetero- and homozygous mutant perinates and adults showed significant differences in shape and size of the cranial vault, face, and basicranium, which were associated with cranial doming and shortening of the basicranium and skull. Although there were also significant shape and size differences associated with the basicranial bones and clear reductions in basicranial ossification in cleared whole-mount samples, there were no significant alterations in chondrocyte cell shape, size, or orientation along the spheno-occipital synchondrosis. Finally, shape differences in the cranial vault and basicranium were interrelated at perinatal stages. These results point toward the possibility that facial shape phenotypes in craniosynostosis may result in part from pleiotropic effects of the causative mutations rather than only from the secondary consequences of the sutural defects, indicating a novel direction of research that may shed light on the etiology of the broad changes in craniofacial morphology observed in craniosynostosis syndromes.