Transformation Products of Tire Rubber Antioxidant 6PPD in Heterogeneous Gas-Phase Ozonation: Identification and Environmental Occurrence.

6PPD, a tire rubber antioxidant, poses substantial ecological risks because it can form a highly toxic quinone transformation product (TP), 6PPD-quinone (6PPDQ), during exposure to gas-phase ozone. Important data gaps exist regarding the structures, reaction mechanisms, and environmental occurrence of TPs from 6PPD ozonation. To address these data gaps, gas-phase ozonation of 6PPD was conducted over 24-168 h and ozonation TPs were characterized using high-resolution mass spectrometry. The probable structures were proposed for 23 TPs with 5 subsequently standard-verified. Consistent with prior findings, 6PPDQ (C18H22N2O2) was one of the major TPs in 6PPD ozonation (∼1 to 19% yield). Notably, 6PPDQ was not observed during ozonation of 6QDI (N-(1,3-dimethylbutyl)-N'-phenyl-p-quinonediimine), indicating that 6PPDQ formation does not proceed through 6QDI or associated 6QDI TPs. Other major 6PPD TPs included multiple C18H22N2O and C18H22N2O2 isomers, with presumptive N-oxide, N,N'-dioxide, and orthoquinone structures. Standard-verified TPs were quantified in roadway-impacted environmental samples, with total concentrations of 130 ± 3.2 µg/g in methanol extracts of tire tread wear particles (TWPs), 34 ± 4 µg/g-TWP in aqueous TWP leachates, 2700 ± 1500 ng/L in roadway runoff, and 1900 ± 1200 ng/L in roadway-impacted creeks. These data demonstrate that 6PPD TPs are likely an important and ubiquitous class of contaminants in roadway-impacted environments.

Screening p-Phenylenediamine Antioxidants, Their Transformation Products, and Industrial Chemical Additives in Crumb Rubber and Elastomeric Consumer Products.

Recently, roadway releases of N,N'-substituted p-phenylenediamine (PPD) antioxidants and their transformation products (TPs) received significant attention due to the highly toxic 6PPD-quinone. However, the occurrence of PPDs and TPs in recycled tire rubber products remains uncharacterized. Here, we analyzed tire wear particles (TWPs), recycled rubber doormats, and turf-field crumb rubbers for seven PPD antioxidants, five PPD-quinones (PPDQs), and five other 6PPD TPs using liquid chromatography-tandem mass spectrometry. PPD antioxidants, PPDQs, and other TPs were present in all samples with chemical profiles dominated by 6PPD, DTPD, DPPD, and their corresponding PPDQs. Interestingly, the individual [PPDQ]/[PPD] and [TP]/[PPD] ratios significantly increased as total concentrations of the PPD-derived chemical decreased, indicating that TPs (including PPDQs) dominated the PPD-derived compounds with increased environmental weathering. Furthermore, we quantified 15 other industrial rubber additives (including bonding agents, vulcanization accelerators, benzotriazole and benzothiazole derivatives, and diphenylamine antioxidants), observing that PPD-derived chemical concentrations were 0.5-6 times higher than these often-studied additives. We also screened various other elastomeric consumer products, consistently detecting PPD-derived compounds in lab stoppers, sneaker soles, and rubber garden hose samples. These data emphasize that PPD antioxidants, PPDQs, and related TPs are important, previously overlooked contaminant classes in tire rubbers and elastomeric consumer products.

Co-Development of a Web Application (COVID-19 Social Site) for Long-Term Care Workers ("Something for Us"): User-Centered Design and Participatory Research Study.

BACKGROUND: Improving confidence in and uptake of COVID-19 vaccines and boosters among long-term care workers (LTCWs) is a crucial public health goal, given their role in the care of elderly people and people at risk. While difficult to reach with workplace communication interventions, most LTCWs regularly use social media and smartphones. Various social media interventions have improved attitudes and uptake for other vaccines and hold promise for the LTCW population. OBJECTIVE: We aimed to develop a curated social web application (interactive website) to increase COVID-19 vaccine confidence (a 3-arm randomized trial is underway). METHODS: Following user-centric design and participatory research approaches, we undertook the following 3 steps: (1) content identification, (2) platform development, and (3) community building. A LTCW and stakeholder advisory group provided iterative input. For content identification (step 1), we identified topics of concern about COVID-19 vaccines via desktop research (published literature, public opinion polls, and social media monitoring), refined by interviewing and polling LTCWs. We also conducted a national online panel survey. We curated and fact-checked posts from popular social media platforms that addressed the identified concerns. During platform development (step 2), we solicited preferences for design and functionality via interviews and user experience testing with LTCWs. We also identified best practices for online community building (step 3). RESULTS: In the interviews (n=9), we identified 3 themes: (1) LTCWs are proud of their work but feel undervalued; (2) LTCWs have varying levels of trust in COVID-19-related information; and (3) LTCWs would welcome a curated COVID-19 resource that is easy to understand and use-"something for us". Through desktop research, LTCW interviews, and our national online panel survey (n=592) we found that participants are interested in information about COVID-19 in general, vaccine benefits, vaccine risks, and vaccine development. Content identification resulted in 434 posts addressing these topic areas, with 209 uploaded to the final web application. Our LTCW poll (n=8) revealed preferences for personal stories and video content. The platform we developed is an accessible WordPress-based social media web application, refined through formal (n=3) and informal user experience testing. Users can sort posts by topic or subtopic and react to or comment on posts. To build an online community, we recruited 3 LTCW "community ambassadors" and instructed them to encourage discussion, acknowledge concerns, and offer factual information on COVID-19 vaccines. We also set "community standards" for the web application. CONCLUSIONS: An iterative, user-centric, participatory approach led to the launch of an accessible social media web application with curated content for COVID-19 vaccines targeting LTCWs in the United States. Through our trial, we will determine if this approach successfully improves vaccine confidence. If so, a similar social media resource could be used to develop curated social media interventions in other populations and with other public health goals.

Cellular Augmentation of Anterior Cruciate Ligament Surgery Is Not Currently Evidence Based: A Systematic Review of Clinical Studies.

PURPOSE: To perform a systematic review of clinical outcome studies exploring cellular augmentation of anterior cruciate ligament (ACL) surgery, including stem cell techniques. METHODS: A systematic search was performed according to the Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines using the Cochrane, PubMed, MEDLINE, SPORTDiscus, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases from 2000 to 2019. The inclusion criteria were clinical studies that reported on ACL surgery augmented with stem cells or cellular therapy and patient-reported outcome measures or graft healing. Risk of bias was assessed using the Cochrane risk-of-bias tool for randomized clinical trials, and nonrandomized trials were assessed using the Methodological Items for Non-randomized Studies (MINORS) tool. Methodologic assessment was performed according to the Modified Coleman Methodology Score. RESULTS: Four studies were found: 2 randomized clinical trials, 1 cohort study with a matched historical control group, and 1 case series. The mean Modified Coleman Methodology Score in these studies was 59, and there was a low risk of bias in 1 study. One study reported outcomes of augmented ACL repair, and 3 studies reported the results of augmented ACL reconstruction. Cellular therapies varied and included concentrated bone marrow aspirate, collagenase/centrifuge processed adipose, and marrow stimulation combined with platelet-rich plasma, as well as cells cultured from allograft bone marrow aspirate. The concentrated bone marrow aspirate and adipose tissue study results did not support their use. The marrow stimulation technique combined with repair led to promising clinical results. The use of allograft cultured cells improved patient-reported outcomes and postoperative radiographic findings. CONCLUSIONS: Augmentation of ACL surgery with cellular therapy is not supported by clinical evidence at this time. LEVEL OF EVIDENCE: Level IV.

Hoarding: A meta-analysis of age of onset.

Hoarding disorder is present in 2-6% of the population and can have an immense impact on the lives of patients and their families. Before its inclusion the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, pathological hoarding was often characterized as a symptom of obsessive-compulsive disorder, and several different diagnostic assessment methods were used to identify and characterize it. Although the age of onset of pathological hoarding is an important epidemiological measure, as clarifying the age of onset of hoarding symptoms may allow for early identification and implementation of evidence-based treatments before symptoms become clinically significant, the typical age of onset of hoarding is still uncertain. To that end, this study is a systematic review and meta-analysis of research published in English between the years 1900 and 2016 containing information on age of onset of hoarding symptoms. Twenty-five studies met inclusion criteria. The mean age of onset of hoarding symptoms across studies was 16.7 years old, with evidence of a bimodal distribution of onset. The authors conclude by discussing practice implications for early identification and treatment.

Regio- and stereoselective hydroxylation of 10-undecenoic acid with a light-driven P450 BM3 biocatalyst yielding a valuable synthon for natural product synthesis.

We report herein the selective hydroxylation of 10-undecenoic acid with a light-activated hybrid P450 BM3 enzyme. Under previously developed photocatalytic reaction conditions, only a monohydroxylated product is detected by gas chromatography. Hydroxylation occurs exclusively at the allylic position as confirmed from a synthesized authentic standard. Investigation into the stereochemistry of the reaction indicates that the R enantiomer is obtained in 85% ee. The (R)-9-hydroxy-10-undecenoic acid obtained enzymatically is a valuable synthon en route to various natural products further expanding the light-activated P450 BM3 biocatalysis and highlighting the advantages over traditional methods.

Multimodal sensory control of motor performance by glycinergic interneurons of the mouse spinal cord deep dorsal horn.

Sensory feedback is integral for contextually appropriate motor output, yet the neural circuits responsible remain elusive. Here, we pinpoint the medial deep dorsal horn of the mouse spinal cord as a convergence point for proprioceptive and cutaneous input. Within this region, we identify a population of tonically active glycinergic inhibitory neurons expressing parvalbumin. Using anatomy and electrophysiology, we demonstrate that deep dorsal horn parvalbumin-expressing interneuron (dPV) activity is shaped by convergent proprioceptive, cutaneous, and descending input. Selectively targeting spinal dPVs, we reveal their widespread ipsilateral inhibition onto pre-motor and motor networks and demonstrate their role in gating sensory-evoked muscle activity using electromyography (EMG) recordings. dPV ablation altered limb kinematics and step-cycle timing during treadmill locomotion and reduced the transitions between sub-movements during spontaneous behavior. These findings reveal a circuit basis by which sensory convergence onto dorsal horn inhibitory neurons modulates motor output to facilitate smooth movement and context-appropriate transitions.

Biotransformation and recovery of the isoflavones genistein and daidzein from industrial antibiotic fermentations.

The objective of this study was to follow the metabolic fate of isoflavone glucosides from the soybean meal in a model industrial fermentation to determine if commercially useful isoflavones could be harvested as coproducts from the spent broth at the end of the fermentation. The isoflavone aglycones, genistein, and daidzein together make up 0.1-0.2 % of the soybean meal by weight but serve no known function in the manufacturing process. After feeding genistein to washed cells of the erythromycin-producing organism, Saccharopolyspora erythraea, the first biotransformation product (Gbp1) was determined by X-ray crystallography to be genistein-7-O-α-rhamnoside (rhamnosylgenistein). Subsequent feeding of rhamnosylgenistein to growing cells of Saccharopolyspora erythraea led to the production of a second biotransformation product, Gbp2. Chromatographic evidence suggested that Gbp2 accumulated in the spent broth of the erythromycin fermentation. When the spent broth was hydrolyzed with acid or industrial enzyme preparations, the isoflavone biotransformation products were returned back to their parental forms, genistein and daidzein, which were then recovered as coproducts. Desirable features of this method are that it does not require modification of the erythromycin manufacturing process or genetic engineering of the producing organism to be put into practice. A preliminary investigation of five additional antibiotic fermentations of industrial importance also found isoflavone coproduct potential.

An erythromycin process improvement using the diethyl methylmalonate-responsive (Dmr) phenotype of the Saccharopolyspora erythraea mutB strain.

The Saccharopolyspora erythraea mutB knockout strain, FL2281, having a block in the methylmalonyl-CoA mutase reaction, was found to carry a diethyl methylmalonate-responsive (Dmr) phenotype in an oil-based fermentation medium. The Dmr phenotype confers the ability to increase erythromycin A (erythromycin) production from 250-300% when the oil-based medium is supplemented with 15 mM levels of this solvent. Lower concentrations of the solvent stimulated proportionately less erythromycin production, while higher concentrations had no additional benefit. Although the mutB strain is phenotypically a low-level erythromycin producer, diethyl methylmalonate supplementation allowed it to produce up to 30% more erythromycin than the wild-type (control) strain-a strain that does not show the Dmr phenotype. The Dmr phenotype represents a new class of strain improvement phenotype. A theory to explain the biochemical mechanism for the Dmr phenotype is proposed. Other phenotypes found to be associated with the mutB knockout were a growth defect and hyper-pigmentation, both of which were restored to normal by exposure to diethyl methylmalonate. Furthermore, mutB fermentations did not significantly metabolize soybean oil in the presence of diethyl methylmalonate. Finally, a novel method is proposed for the isolation of additional mutants with the Dmr phenotype.

Fluorescent reporters of monoamine transporter distribution and function.

Serotonin is a monoamine serving as a chemical messenger in diverse brain regions, as well as in blood and various other organs. We synthesized six ethylamine functionalized fluorophores as fluorescent probes for serotonin. The one with best spectral properties and aqueous solubility, 6-amino-2-(2-aminoethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione, was studied in detail both in vivo and in vitro. It was shown to act as a ligand for serotonin transporter (SERT) without acute cerebral or cardiovascular toxicity or adverse effects. Fluorescent serotonin analogs can be used for direct visualization of SERT distribution and activity in live tissue.

[Morphology of the species Hyphessobrycon, heterorhabdus group (Characiformes: Characidae) in Colombia]. / Morfología de las especies de Hyphessobrycon (Characiformes: Characidae), grupo heterorhabdus, en Colombia.

Hyphessobrycon is the most numerous and morphologically complex genus of Characidae, and includes 18 species reported for Colombia, from which thirteen belong to the heterorhabdus-group different methods have been proposed for species identification within this genus. This study used these species to undertake a morphogeometric analysis by the Box Truss and Thin Plate Splin (TPS) methods; 13 homologous landmarks type I and three type II were used. The result of cluster analysis indicated that these species are represented by two big groups: robust and thin. The uniform and non uniform components, and the principal warps (WP) and partial warps (Wparc), described the shape changes related to body depth, involving relative displacements of the appendicular skeleton and the cephalic region. All species were characterized by allometric growth with the exception of Hyphessobrycon mavro, who presented an isometry between the landmarks 6-7. Two new measures are proposed for species discrimination in the group (snout-supraoccipital spine distance and supraoccipital spine-pelvic fin).

A ubiquitous tire rubber-derived chemical induces acute mortality in coho salmon.

In U.S. Pacific Northwest coho salmon (Oncorhynchus kisutch), stormwater exposure annually causes unexplained acute mortality when adult salmon migrate to urban creeks to reproduce. By investigating this phenomenon, we identified a highly toxic quinone transformation product of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), a globally ubiquitous tire rubber antioxidant. Retrospective analysis of representative roadway runoff and stormwater-affected creeks of the U.S. West Coast indicated widespread occurrence of 6PPD-quinone (<0.3 to 19 micrograms per liter) at toxic concentrations (median lethal concentration of 0.8 ± 0.16 micrograms per liter). These results reveal unanticipated risks of 6PPD antioxidants to an aquatic species and imply toxicological relevance for dissipated tire rubber residues.

[Morphogeometry of fishes in the genus Hyphessobrycon (Characiformes: Characidae), heterorhabdus group, from Venezuela]. / Morfogeometría de los peces del género Hyphessobrycon (Characiformes: Characidae), grupo heterorhabdus, en Venezuela.

Hyphessobrycon is the most numerous and morphologically complex genus of Characidae, that includes 122 valid species, 17 of which are present in Venezuela. Different methods have been proposed for species identification within this genus. We present a morphometric analysis for the species Hyphessobrycon, heterorhabdus group. A total number of 310 individuals were photographed and analyzed by means of Box Truss method. The combination of 16 homologous landmarks and the design of Box Truss yielded 28 measurements. The Principal Components Analysis (PCA) indicated that the differences between the species are related to the distance between snout and the supraoccipital (81.7%), and between the supraoccipital and the base of the pectoral fin (11.87%). All species showed allometric growth except for Hyphessobrycon tuyensis, which resulted isometric in the Box Truss I. The partial deformations describe the form differences related to the cephalic region and the body depth. The great body form similarity is related to the phylogeny and biogeography of these species.

Subacute COVID-19 Infection Presenting as Indolent Large Pericardial Effusion.

Reports of complications as a result of COVID-19 infection are emerging since the virus became a pandemic. Although not fully understood, reports show that the COVID-19 virus has shown acute pericardial involvement resulting from this infection. It can cause a wide range of manifestations from minimal effusion to large effusion with tamponade; however, there is little or no data on an indolent course of COVID-19 infection and its resulting manifestations. Here we describe a patient who had minimal disease symptoms for weeks, resulting in sizeable pericardial effusion formation.

Truck Drivers' Cigarette Smoking and Preferred Smoking Cessation Methods.

INTRODUCTION: Some studies show that truck drivers use tobacco and other stimulants to stay awake as they drive. Despite their increased risks for many of tobacco-related health disparities, there is limited engagement of truck drivers in smoking cessation programs. The objective of this study was to describe smoking characteristics and identify their preferred smoking cessation methods among truck drivers. METHODS: This was a cross-sectional mixed methods study. Participants were truck drivers recruited at trucking companies in Utah in 2019. Participants were either individually interviewed (n = 4), or filled out a survey (n = 33). We conducted qualitative data analysis of the interviews followed by descriptive statistics of smoking and cessation characteristics from the survey. RESULTS: Reasons for smoking included, staying awake, stress reduction, or something to do while driving. Of the drivers surveyed, 68.8% were daily smokers while 97% had smoked at least 100 cigarettes in their life time. The mean number of cigarettes per day (cpd) was 15.7, and 25 among those who had 10 or more cpd. Sixty-one percent had made at least a quit attempt. In addition to counseling or brief advice, 68% reported interest in using Nicotine Replacement Therapy (NRT) either as gum or patch to help them quit. 21% reported interest in telephone text messaging to engage them in treatment. CONCLUSION: Cigarette smoking is a public health problem among truck drivers. Our findings suggest that truck drivers are interested in quitting smoking. Evidence based interventions tailored to this population are needed to help them quit and reduce their smoking-related morbidity.

Interpersonal patterns in close relationships: the role of sociotropy-autonomy.

Sociotropy and autonomy are conceptualized as two personality dimensions that relate to an individual's vulnerability to depression. Sociotropy is characterized as an excessive investment in interpersonal relationships and autonomy is characterized as an excessive concern with personal achievement and control over the environment. The present research project consisted of two studies examining the relationships between sociotropy-autonomy and interpersonal patterns in close relationships. Data collected via self-report and behavioural observations suggested that highly sociotropic individuals have a tendency to be high in control and low in affiliation towards individuals who are close to them. In contrast, the data suggested that highly autonomous individuals may be low in both control and affiliation towards people who are close to them. These findings are discussed in the context of the literature regarding the interpersonal characteristics of sociotropic and autonomous individuals.

[Appendiceal mucocele misdiagnosed with infected urachal cyst: a differential diagnosis to keep in mind]. / Mucocele apendicular confundido con quiste de uraco infectado: un diagnóstico diferencial a tener en cuenta.

OBJECTIVE: To report one case of appendiceal mucocele misdiagnosed with an infected urachal cyst and to review their differential diagnosis, treatment and prognosis. PATIENT: We report the case of a 74-year-old-male with abdominal pain, fever and dysuria. Hypogastric abscess image in ultrasonography and CT. Percutaneous drainage and antibiotic therapy. Opaque enema, colonoscopy and cystoscopy were normal. RESULTS: Exploratory laparotomy and resection of a large cecum-fixed mass, independent to the bladder. Appendectomy and cecectomy. Pathology showed an appendiceal mucinous cystoadenoma (mucocele). CONCLUSIONS: Appendiceal mucoceles and urachal cysts are uncommon, mostly asymptomatic. Cystoadenoma or cystoadenocarcinoma mucoceles are large and can reach the midline, confounding with urachal cysts. Diagnosis by ultrasonography and/or CT. Surgical treatment in both, keeping the mucocele intact during operation to avoid the risk of pseudomyxoma peritonei.

Repair of Forearm Muscle Herniation Using Local Fascial Flap: A Case Report.

Forearm muscle herniation is a rare but known cause of symptomatic pain in the upper extremity caused by compression or strangulation of the muscle belly through a defect in the overlying fascia. Because of the rarity of this condition, optimal treatment is still widely unknown and debated. To date, there are various treatment methods published, including rest, physiotherapy, primary repair, fasciotomy, fascia lata inlay, onlay or wrap-around, mesh graft, and acellular porcine collagen matrix. In this study, a 61-year old man underwent an ulnar nerve transposition to correct cubital tunnel syndrome, resulting in subsequent symptoms of muscle herniation on the volar aspect of the forearm. Prominent muscle herniation was visible a few weeks after the onset of symptoms and surgical correction of the fascial defect was performed using a local fascial flap. Postoperatively, the patient's herniation symptoms resolved without signs of ulnar nerve entrapment. The rationale for this treatment option is discussed.

Other Language Proficiency Predicts Unique Variance in Verbal Fluency Not Accounted for Directly by Target Language Proficiency: Cross-Language Interference?

The purpose of the study was to investigate cross-language effects in verbal fluency tasks where participants name in English as many exemplars of a target as they can in one minute. A series of multiple regression models were used that employed predictors such as self-rated proficiency in English, self-rated proficiency in a language other than English, a picture naming task used to measure productive vocabulary, the percentage of English use, and the frequency of language switching. The main findings showed that self-rated proficiency in the non-English language accounted for unique variance in verbal fluency that was not accounted for directly by self-rated proficiency in English. This outcome is consistent with cross-language interference, but is also consistent with an account that assumes bilingual disadvantages in verbal fluency and picture naming are due to bilinguals having weaker links between semantic concepts and their phonological form. The present study is also discussed in terms of a broader framework that questions whether domain-general inhibition exists and also whether it plays an important role in bilingual language control.