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.

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.

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.

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.

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.

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.

An update on intracerebral stem cell grafts.

INTRODUCTION: Primary neurological disorders are notoriously debilitating and deadly, and over the past four decades stem cell therapy has emerged as a promising treatment. Translation of stem cell therapies from the bench to the clinic requires a better understanding of delivery protocols, safety profile, and efficacy in each disease. Areas covered: In this review, benefits and risks of intracerebral stem cell transplantation are presented for consideration. Milestone discoveries in stem cell applications are reviewed to examine the efficacy and safety of intracerebral stem cell transplant therapy for disorders of the central nervous system and inform design of translatable protocols for clinically feasible stem cell-based treatments. Expert commentary: Intracerebral administration, compared to peripheral delivery, is more invasive and carries the risk of open brain surgery. However, direct cell implantation bypasses the blood-brain barrier and reduces the first-pass effect, effectively increasing the therapeutic cell deposition at its intended site of action. These benefits must be weighed with the risk of graft-versus-host immune response. Rigorous clinical trials are underway to assess the safety and efficacy of intracerebral transplants, and if successful will lead to widely available stem cell therapies for neurologic diseases in the coming years.

Immunotherapy Toxicities: 
A New Electronic Documentation Template to Improve Patient Care.

BACKGROUND: Emerging immunotherapies are associated with numerous toxicities. Although traditional health records allow nurses to document system-based assessments, few offer immunotherapy-based documentation templates to assess and grade toxicities.
. OBJECTIVES: The aim of this article is to present the development of a standardized template for documenting genetically modified cellular product-related toxicities in an electronic health record (EHR).
. METHODS: Through interprofessional collaboration, a documentation template for genetically modified cellular product-related toxicities was developed in an EHR, allowing for standardized documentation, data reporting, and tracking of immune-related toxicities. 
. FINDINGS: The documentation template has enhanced the quality and safety of practice at the authors' institution and provides a framework for other nursing units when initiating immunotherapy care.
.

Co-occurring behavioral difficulties in children with severe feeding problems: A descriptive study.

BACKGROUND: Recent literature highlights the association between behavioral difficulties and the presence of feeding problems in children with an Autism Spectrum Disorder (ASD) relative to children with ASD without feeding problems. However, it is not clear to what extent behavior problems (outside of the meal setting) occur in children with feeding problems without comorbid ASD. AIMS: The purpose is to describe co-occurring behavioral difficulties of a sample of children with severe food refusal/selectivity and examine potential predictors of behavioral difficulties outside of the meal context. METHOD AND PROCEDURES: The medical charts of fifty-four patients were reviewed and data were collected on the frequency of caregiver coaching and/or behavioral intervention outside of the meal context. Age, presence of developmental delay/autism, and type of feeding problem were examined as potential predictors of behavioral support. OUTCOME AND RESULTS: Approximately half of the sample received coaching or individualized intervention. The percentage of caregivers who received individualize coaching were similar across groups. Younger age at admission was a predictor of individual caregiver coaching. Presence of delay/ASD, age, and type of feeding problems were not significant predictors for individualized treatment programing. CONCLUSION AND IMPLICATIONS: These data provide evidence of difficult caregiver-child interactions that occurs outside of the meal context for some children with severe feeding difficulties and suggest that this association may not be exclusive to children with ASD.

Random transposon mutagenesis of the Saccharopolyspora erythraea genome reveals additional genes influencing erythromycin biosynthesis.

A single cycle of strain improvement was performed in Saccharopolyspora erythraea mutB and 15 genotypes influencing erythromycin production were found. Genotypes generated by transposon mutagenesis appeared in the screen at a frequency of ~3%. Mutations affecting central metabolism and regulatory genes were found, as well as hydrolases, peptidases, glycosyl transferases and unknown genes. Only one mutant retained high erythromycin production when scaled-up from micro-agar plug fermentations to shake flasks. This mutant had a knockout of the cwh1 gene (SACE_1598), encoding a cell-wall-associated hydrolase. The cwh1 knockout produced visible growth and morphological defects on solid medium. This study demonstrated that random transposon mutagenesis uncovers strain improvement-related genes potentially useful for strain engineering.

Perfiles de funcionamiento comportamental en una población de niños con problemas de aprendizaje / Behavioral profiles operating in a population of children with learning disabilities

En el marco de un programa de intervención para favorecer la escolarización de niños de poblaciones vulnerables desde un punto de vista psicosocial, donde el psiquiatra pediátrico participa activamente en un equipo conformado también por psicólogos, psicomotricistas, fonoaudiólogos y maestros especializados, se mide la asociación entre patología conductual y problemas del aprendizaje. Se destaca la construcción de una escala de funcionamiento escolar, administrada al maestro de clase, aplicada a 4.642 niños, que confirma estadisticamente su unidimensionalidad para medir este atributo, donde los ítems académicos y comportamentales contribuyen a la escolarización y la aplicación de un protocolo de historia clínica médico-psicológica, aplicada a 334 niños seleccionados a través de la escala, que muestran la frecuencia de agrupaciones sintomáticas que deben tomarse en cuenta para que los abordajes terapéuticos sean eficientes.

Inappropriate mealtime behavior: the effects of noncontingent access to preferred tangibles on responding in functional analyses.

An understanding of the functional variables associated with inappropriate mealtime behavior (IMB) is critical to developing an effective and efficient treatment for food refusal. To this aim, functional analysis methodology has been modified for the meal context, and previous research has shown that multiple sources of reinforcement maintain IMB. Functional analysis literature, related to severe problem behavior, suggests that access to preferred stimuli may abolish or compete with social reinforcers in some cases. The role of noncontingent access to preferred stimuli during the assessment of IMB has not been evaluated. The purpose of the current study was to examine the effects noncontingent access to preferred toys/activities on IMB in the presence and absence of social consequences. The specific aims were to evaluate: (1) levels of IMB when the spoon is held stationary at the child's lips when preferred tangible stimuli are present noncontingently vs. absent; (2) levels of IMB when social consequences were provided contingent upon IMB when preferred tangible stimuli are present noncontingently vs. absent. For many participants, levels of IMB were reduced with the inclusion of preferred toys/activities; while for one, levels of IMB increased. Possible implications of these findings on functional analyses of IMB will be discussed.

Complementary expression of EphA7 and SCO-spondin during posterior commissure development.

Bilaterally symmetric organisms need to exchange information between the two sides of their bodies in order to integrate sensory inputs and coordinate motor control. This exchange occurs through commissures formed by neurons that project axons across the midline to the contralateral side of the central nervous system. The posterior commissure is the first transversal axonal tract of the embryonic vertebrate brain. It is located in the dorsal portion of the prosomere 1, at the caudal diencephalon. The axons of the posterior commissure principally come from neurons of ventrolateral and dorsolateral pretectal nuclei (parvocellular and magnocellular nucleus of the posterior commissure, respectively) that extend their axons toward the dorsal region. The trajectory of these axons can be divided into the following three stages: (1) dorsal axon extension towards the lateral roof plate; (2) fasciculation in the lateral roof plate; and (3) midline decision of turning to the ipsilateral side or continuing to the opposite side. The mechanisms and molecules that guide the axons during these steps are unknown. In the present work, immunohistochemical and in situ hybridization analyses were performed, with results suggesting the participation of EphA7 in guiding axons from the ventral to the dorsal region of the prosomere 1 through the generation of an axonal corridor limited by repulsive EphA7 walls. At the lateral roof plate, the axons became fasciculated in presence of SCO-spondin until reaching the midline. Finally, EphA7 expression was observed in the diencephalic midline roof plate, specifically in the region where some axons turn to the ipsilateral side, suggesting its participation in this decision. In summary, the present work proposes a mechanism of posterior commissure formation orchestrated by the complementary expression of the axon guidance cues SCO-spondin and EphA7.

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.