An introduction to environmental neurotoxicology: Lessons from a clinical perspective.

In 1992, the Committee on Neurotoxicology and Models for Assessing Risk of the National Academy of Sciences in Washington DC focused with a scientific perspective on the identification of substances with neurotoxic potential, studies of exposed populations, risk assessment, and biologic markers of disease. This Committee recommended: "all physicians should be trained to take a thorough occupational-exposure history and to be aware of other possible sources of toxic exposure". Although convened after several outbreaks of neurotoxic syndromes, clinical neurological considerations were lacking. After defining keys words, namely Environment, Neurotoxicology and Neurotoxicants, we present some demonstrative cases; e.g., the Epidemic Neuropathy in Cuba, Minamata disease, ALS/PDC on Guam, and the ALS hot spot in the French Alps. Always with a clinical and practical approach, we will then review the milieux that contain and convey potential neurotoxicants, the different exposure routes and the clinical presentations. Drawing lessons from clinical cases, we offer some thoughts concerning the future of Environmental Neurotoxicology (ENT). Pointing notably to the diffuse chemical contamination of ecosystems and living beings, including Homo sapiens, we question the real impact of agents with neurotoxic potential on the human brain, considering the effects, for example, of air pollution, endocrine disruptors and nanoparticles. Concern is expressed over the lack of knowledge of the non-monotonic kinetics of many of these chemicals, the major concern being related to mixtures and low-dose exposures, as well as the delayed appearance in clinical expression of prevalent neurodegenerative diseases.

Developing education in environmental health and medicine focusing on neurology: Initiatives in Sweden (the UPRISE model), France, and Turkey.

BACKGROUND: The role of environmental factors in neurological disorders constitutes a topic of increasing importance. Teaching in European universities should expand and update this field gaining future health professionals including adjacent disciplines. AIM: To describe recent efforts to create courses that cover crucial interdisciplinary content that we believe should be included in modern education, and to adapt modern pedagogic strategies. METHODS: In collaboration with RISE (Rencontres Internationales Santé Environnement), elective courses focused on Environmental Health and Medicine (EHM) were developed, in France, Sweden, and Turkey. The courses combined classic teaching methods and new pedagogic and digital solutions to create environment-related health awareness and facilitate future interprofessional collaboration in this field. RESULTS: UPRISE is an innovative elective course introduced in 2020 in Sweden's Uppsala University with the participation of lecturers from several countries and aim to recruit students from different universities. A total of 45, mainly female students (68%), participated in the course. In Strasbourg, France, a novel course on environmental medicine was held in 2019-2023 and examined 90 students, of which more than half were female. Nine graduate nurse students in Turkey attended ten seminar series focused on EHM. Overall, students expressed satisfaction with the courses. CONCLUSIONS: This European project for courses in higher education arising from RISE was met with appreciation and challenges from academic institutions. However, due to considerable efforts to introduce the EHM concept, a unique compulsory course for all medical students in the second year of training started in 2023 in all French medical faculties. In 2023, UPRISE was integrated into ENLIGHT, the European University Network to promote equitable quality of Life, sustainability, and Global engagement through Higher education Transformation.

Electrifying Hydroformylation Catalysts Exposes Voltage-Driven C-C Bond Formation.

Electrochemical reactions can access a significant range of driving forces under operationally mild conditions and are thus envisioned to play a key role in decarbonizing chemical manufacturing. However, many reactions with well-established thermochemical precedents remain difficult to achieve electrochemically. For example, hydroformylation (thermo-HFN) is an industrially important reaction that couples olefins and carbon monoxide (CO) to make aldehydes. However, the electrochemical analogue of hydroformylation (electro-HFN), which uses protons and electrons instead of hydrogen gas, represents a complex C-C bond-forming reaction that is difficult to achieve at heterogeneous electrocatalysts. In this work, we import Rh-based thermo-HFN catalysts onto electrode surfaces to unlock electro-HFN reactivity. At mild conditions of room temperature and 5 bar CO, we achieve Faradaic efficiencies of up to 15% and turnover frequencies of up to 0.7 h-1. This electro-HFN rate is an order of magnitude greater than the corresponding thermo-HFN rate at the same catalyst, temperature, and pressure. Reaction kinetics and operando X-ray absorption spectroscopy provide evidence for an electro-HFN mechanism that involves distinct elementary steps relative to thermo-HFN. This work demonstrates a step-by-step experimental strategy for electrifying a well-studied thermochemical reaction to unveil a new electrocatalyst for a complex and underexplored electrochemical reaction.

Influence of signal-to-noise ratio on DoLP and AoP measurements during reflectance-mode division-of-focal plane Stokes polarimetry of biological tissues.

Stokes polarimeter based endoscopes are emerging as an area of technology where polarization imaging can greatly impact clinical care by improving diagnostic tools without the use of exogenous contrast. Image acquisition in minimally invasive surgical settings is often beset by inherently limited illumination. A comprehensive analysis of how signal-to-noise (SNR) propagates through Stokes polarimetric outcomes such as degree of linear polarization (DoLP) and angle of polarization (AoP) in low light is important for future interpretation of data acquired in low-light conditions. A previously developed theoretical model of quantitative polarized light imaging (QPLI) analysis described SNR as a function of both incident light intensity and DoLP. When polarized light interacts with biological tissues, the resultant DoLP of exiting light is dependent on the underlying tissue microstructure. Therefore, in this study we explore how low light impacts SNR of QPLI outcomes of DoLP and AoP differently in tissue phantoms of varying microstructures. Data are compared to theoretical solutions of SNR of DoLP and AoP. Tissues were additionally loaded to varying magnitudes of strain to investigate how variable SNR affects the ability to discern dynamic realignment in biological tissues. We observed a high degree of congruency between experimental and theoretical data, with SNR depending on both light intensity and DoLP. Additionally, we found that AoP may have a greater resilience to noise overall than DoLP and, as such, may be particularly useful in conditions where light is inherently limited.

Fast absorbing gut sutures in dermatologic surgery: a systematic review and meta-analysis.

INTRODUCTION: Fast gut cutaneous sutures have become more prominent due to their low tissue reactivity, rapid absorption, and elimination of suture removal visits. It is not known how fast gut sutures compare to other closure modalities. METHODS: A comprehensive literature review was conducted to identify randomized controlled trials comparing fast gut sutures to alternative closure methods during dermatologic surgery. Data collected included patient and physician assessed cosmetic outcome as well as standardized complication rates. RESULTS: Six studies were included in final analysis and reported on 208 patients. Fast gut sutures were associated with lower physician opinions of final scar when compared to polypropylene sutures (SMD 0.438; 95% CI 0.082 to 0.794). No differences existed between physician opinion of fast gut sutures and cyanoacrylate tissue adhesive (SMD - 0.024; 95% CI - 0.605 to 0.556). Complications with fast gut suture placement were rare, and included infection, dehiscence, and hematomas. Fast gut sutures were less likely to experience wound dehiscence than tissue adhesive (p = 0.01). CONCLUSION: If no contraindications to polypropylene sutures exist, they may provide superior cosmetic outcomes compared to fast gut sutures. Further research is required to better quantify cosmetic outcomes and optimal use of fast gut sutures.

Reinforced tissue matrix to strengthen the abdominal wall following reversal of temporary ostomies or to treat incisional hernias.

BACKGROUND: Abdominal wall deficiencies or weakness are a common complication of temporary ostomies, and incisional hernias frequently develop after colostomy or ileostomy takedown. The use of synthetic meshes to reinforce the abdominal wall has reduced hernia occurrence. Biologic meshes have also been used to enhance healing, particularly in contaminated conditions. Reinforced tissue matrices (RTMs), which include a biologic scaffold of native extracellular matrix and a synthetic component for added strength/durability, are designed to take advantage of aspects of both synthetic and biologic materials. To date, RTMs have not been reported to reinforce the abdominal wall following stoma reversal. AIM: To evaluate the effectiveness of using an RTM to reinforce the abdominal wall at stoma takedown sites. METHODS: Twenty-eight patients were selected with a parastomal and/or incisional hernia who had received a temporary ileostomy or colostomy for fecal diversion after rectal cancer treatment or trauma. Following hernia repair and proximal stoma closure, RTM (OviTex® 1S permanent or OviTex® LPR) was placed to reinforce the abdominal wall using a laparoscopic, robotic, or open surgical approach. Post-operative follow-up was performed at 1 month and 1 year. Hernia recurrence was determined by physical examination and, when necessary, via computed tomography scan. Secondary endpoints included length of hospital stay, time to return to work, and hospital readmissions. Evaluated complications of the wound/repair site included presence of surgical site infection, seroma, hematoma, wound dehiscence, or fistula formation. RESULTS: The observational study cohort included 16 male and 12 female patients with average age of 58.5 years ± 16.3 years and average body mass index of 26.2 kg/m2 ± 4.1 kg/m2. Patients presented with a parastomal hernia (75.0%), incisional hernia (14.3%), or combined parastomal/incisional hernia (10.7%). Using a laparoscopic (53.6%), robotic (35.7%), or open (10.7%) technique, RTMs (OviTex® LPR: 82.1%, OviTex® 1S: 17.9%) were placed using sublay (82.1%) or intraperitoneal onlay (IPOM; 17.9%) mesh positioning. At 1-month and 1-year follow-ups, there were no hernia recurrences (0%). Average hospital stays were 2.1 d ± 1.2 d and return to work occurred at 8.3 post-operative days ± 3.0 post-operative days. Three patients (10.7%) were readmitted before the 1-month follow up due to mesh infection and/or gastrointestinal issues. Fistula and mesh infection were observed in two patients each (7.1%), leading to partial mesh removal in one patient (3.6%). There were no complications between 1 month and 1 year (0%). CONCLUSION: RTMs were used successfully to treat parastomal and incisional hernias at ileostomy reversal, with no hernia recurrences and favorable outcomes after 1-month and 1-year.

Building a Partnership Between a University and Local High School to Foster and Grow Interest in Biomedical Sciences and Engineering.

To help foster interest in science, technology, engineering, and math (STEM), it is important to develop opportunities that excite and teach young minds about STEM-related fields. Over the past several years, our university-based research group has sought to help grow excitement around the biomechanics and biomedical engineering fields. The purposes of this technical brief are to (1) discuss the development of a partnership built between a St. Louis area high school and biomechanics research lab and (2) provide practical guidance for other researchers looking to implement a long-term outreach program. The partnership uses three different outreach opportunities. The first opportunity consisted of 12th-grade students visiting university research labs for an up-close perspective of ongoing biomedical research. The second opportunity was a biomedical research showcase where research-active graduate students traveled to the high school to perform demonstrations. The third opportunity consisted of a collaborative capstone project where a high school student was able to carry out research directly in a university lab. To date, we have expanded our reach from 19 students to interacting with over 100 students, which has yielded increased interest in STEM related research. Our postprogram survey showed that outreach programs such as the one described herein can increase interest in STEM within all ages of high school students. Building partnerships between high schools and university researchers increases the interest in STEM amongst high school students, and gives graduate students an outlet to present work to an eager-to-learn audience.

1,4-Dihydropyridine Anions as Potent Single-Electron Photoreductants.

We report the use of simple 1,4-dihydropyridine anions as a general platform for promoting single-electron photoreductions. In the presence of a mild base, 1,4-dihydropyridines were shown to effectively promote the hydrodechlorination and borylation of aryl chlorides and the photodetosylation of N-tosyl aromatic amines under visible light irradiation. Our studies also demonstrate that the C4 substituent can influence the reactivity of these anions, reducing unwanted side reactions like hydrogen atom transfer and back-electron transfer.

Multi-organ phenotypes in mice lacking latent TGFß binding protein 2 (LTBP2).

BACKGROUND: Latent TGFß binding protein-2 (LTBP2) is a fibrillin 1 binding component of the microfibril. LTBP2 is the only LTBP protein that does not bind any isoforms of TGFß, although it may interfere with the function of other LTBPs or interact with other signaling pathways. RESULTS: Here, we investigate mice lacking Ltbp2 (Ltbp2-/- ) and identify multiple phenotypes that impact bodyweight and fat mass, and affect bone and skin development. The alterations in skin and bone development are particularly noteworthy since the strength of these tissues is differentially affected by loss of Ltbp2. Interestingly, some tissues that express high levels of Ltbp2, such as the aorta and lung, do not have a developmental or homeostatic phenotype. CONCLUSIONS: Analysis of these mice show that LTBP2 has complex effects on development through direct effects on the extracellular matrix (ECM) or on signaling pathways that are known to regulate the ECM.

Vitamin B12 -Photocatalyzed Cyclopropanation of Electron-Deficient Alkenes Using Dichloromethane as the Methylene Source.

The cyclopropyl group is of great importance in medicinal chemistry, as it can be leveraged to influence a range of pharmaceutical properties in drug molecules. This report describes a Vitamin B12 -photocatalyzed approach for the cyclopropanation of electron-deficient alkenes using dichloromethane (CH2 Cl2 ) as the methylene source. The reaction proceeds in good to excellent yields under mild conditions, has excellent functional group compatibility, and is highly chemoselective. The scope could also be extended to the preparation of D2 -cyclopropyl and methyl-substituted cyclopropyl adducts starting from CD2 Cl2 and 1,1-dichloroethane, respectively.

Most Online Resources for Home Suture Removal are Poor in Quality.

Introduction: At home suture or staple removal can be stressful for patients and may lead some to seek out additional instruction via online resources as an adjunct to what was explained to them by their provider. The purpose of this study was to examine the existing online resources available to patients who may be interested in or have been instructed to remove sutures at home after a simple procedure, such as a skin biopsy or excision. Methods: A systematic search was conducted using internet search engines to identify videos and webpages targeting at home suture removal instruction. The DISCERN instrument was used to evaluate the information quality of each included resource. Results: There was no statistically significant difference between average DISCERN scores for videos and webpage resources, and the majority were rated poor in quality. Conclusions: The online resources for at home suture and staple removal were often not comprehensive and were below the standard quality for written information. Health care providers should consider referring their patients to validated online sources for suture removal to prevent misinformation and improve patient safety.

Effect of matrix properties on transmission and reflectance mode division-of-focal-plane Stokes polarimetry.

Significance: Division-of-focal-plane Stokes polarimetry is emerging as a powerful tool for the microstructural characterization of soft tissues. How individual extracellular matrix (ECM) properties influence polarimetric signals in reflectance or transmission modes of quantitative polarized light imaging (QPLI) is not well understood. Aim: We aimed to investigate how ECM properties affect outcomes obtained from division-of-focal-plane polarimetric imaging in reflectance or transmission modes. Approach: Tunable collagen gel phantoms were used to modulate ECM properties of anisotropy, collagen density, crosslinking, and absorber density; the effects of degree of linear polarization (DoLP) and angle of polarization (AoP) on polarimetry outcomes were assessed. A model biological tissue (i.e., bovine tendon) was similarly imaged and evaluated using both reflectance and transmission modes. Results: Reflectance QPLI resulted in decreased DoLP compared with transmission mode. A 90 deg shift in AoP was observed between modes but yielded similar spatial patterns. Collagen density had the largest effect on outcomes besides anisotropy in both imaging modes. Conclusions: Both imaging modes were sufficiently sensitive to detect structural anisotropy differences in gels of varying fiber alignment. Conclusions drawn from phantom experiments should carry over when interpreting data from more complex tissues and can help provide context for interpretation of other Stokes polarimetry data.

Free Speech or Free to Hate?: Anti-LGBTQ+ Discourses in LGBTQ+-Affirming Spaces on Gab Social.

This article presents a critical discourse analysis of groups on the free speech social media platform Gab that were intended to be LGBTQ+-friendly but became spaces of queerphobia. Results indicate that Gab users deployed discourses of difference to situate the platform as heteronormative and to denigrate the LGBTQ+ community. In particular, discourses utilized in the name of free speech were used to establish LGBTQ+ individuals as abominations, undergird hegemonic masculinity, and marginalize queer folk by reducing them to sex acts and sex organs. This study provides a better understanding of the (in)efficacy of "free speech" as a content moderation policy and unpacks how anti-LGBTQ+ hate speech spreads in digital spaces.

Efficacy of Flowable Collagen Hemostat Evaluated in Preclinical Models of Liver Injury and Spinal Cord Exposure.

Introduction: Excessive bleeding in trauma and surgical settings leads to increased operative time, reoperation rates, and overall healthcare costs. A wide range of hemostatic agents have been developed to control bleeding that can vary considerably in type of hemostatic action, ease of application, cost, risk of infection, and dependence on patient coagulation. Microfibrillar collagen-based hemostatic materials (MCH) have yielded beneficial results in a variety of applications. Methods: A new flowable collagen product, containing a modified MCH flour, but in a more convenient flowable delivery system, was evaluated for hemostatic efficacy in preclinical models of solid organ injury and spinal cord exposure. The primary objective of this study was to compare the hemostatic potential and local tissue responses to this novel, flowable collagen-based hemostatic agent to the original flour formulation to confirm that the new method of delivery did not interfere with the hemostatic properties of the MCH flour. Results: When observed visually, the flowable MCH flour mixed with saline (FL) provided more precise application and uniform coverage to injured tissues compared to the dry MCH flour alone (F0). All of the treatments (FL, F0, and gauze) exhibited comparable Lewis bleed grade at all three time points evaluated in the capsular resection liver injury model (bleed grade: 1.0-1.3; p> 0.05 in all cases). FL and F0 exhibited comparable 100% acute hemostatic efficacy and similar long-term histomorphological properties (up to 120 days) in a capsular resection liver injury in pigs, while gauze resulted in significantly lower rates of acute hemostatic efficacy (8-42%, p<0.05 in all cases). In an ovine model of dorsal laminectomy and durotomy, FL and F0 again exhibited comparable results without any neurological effects. Conclusion: Flowable microfibrillar collagen was shown to yield favorable short- and long-term outcomes in two representative applications where hemostatic efficacy is critical to surgical success.

Guidelines for ex vivo mechanical testing of tendon.

Tendons are critical for the biomechanical function of joints. Tendons connect muscles to bones and allow for the transmission of muscle forces to facilitate joint motion. Therefore, characterizing the tensile mechanical properties of tendons is important for the assessment of functional tendon health and efficacy of treatments for acute and chronic injuries. In this guidelines paper, we review methodological considerations, testing protocols, and key outcome measures for mechanical testing of tendons. The goal of the paper is to present a simple set of guidelines to the nonexpert seeking to perform tendon mechanical tests. The suggested approaches provide rigorous and consistent methodologies for standardized biomechanical characterization of tendon and reporting requirements across laboratories.

A chromosome-scale reference of Chenopodium watsonii helps elucidate relationships within the North American A-genome Chenopodium species and with quinoa.

Quinoa (Chenopodium quinoa), an Andean pseudocereal, attained global popularity beginning in the early 2000s due to its protein quality, glycemic index, and high fiber, vitamin, and mineral contents. Pitseed goosefoot (Chenopodium berlandieri), quinoa's North American free-living sister species, grows on disturbed and sandy substrates across the North America, including saline coastal sands, southwestern deserts, subtropical highlands, the Great Plains, and boreal forests. Together with South American avian goosefoot (Chenopodium hircinum) they comprise the American tetraploid goosefoot complex (ATGC). Superimposed on pitseed goosefoot's North American range are approximately 35 AA diploids, most of which are adapted to a diversity of niche environments. We chose to assemble a reference genome for Sonoran A-genome Chenopodium watsonii due to fruit morphological and high (>99.3%) preliminary sequence-match similarities with quinoa, along with its well-established taxonomic status. The genome was assembled into 1377 scaffolds spanning 547.76 Mb (N50 = 55.14 Mb, L50 = 5), with 94% comprised in nine chromosome-scale scaffolds and 93.9% Benchmarking Universal Single-Copy Orthologs genes identified as single copy and 3.4% as duplicated. A high degree of synteny, with minor and mostly telomeric rearrangements, was found when comparing this taxon with the previously reported genome of South American C. pallidicaule and the A-subgenome chromosomes of C. quinoa. Phylogenetic analysis was performed using 10,588 single-nucleotide polymorphisms generated by resequencing a panel of 41 New World AA diploid accessions and the Eurasian H-genome diploid Chenopodium vulvaria, along with three AABB tetraploids previously sequenced. Phylogenetic analysis of these 32 taxa positioned the psammophyte Chenopodium subglabrum on the branch containing A-genome sequences from the ATGC. We also present evidence for long-range dispersal of Chenopodium diploids between North and South America.

Early Joint Use Following Elbow Dislocation Limits Range-of-Motion Loss and Tissue Pathology in Posttraumatic Joint Contracture.

BACKGROUND: Simple elbow dislocation occurs at an incidence of 2.9 to 5.21 dislocations per 100,000 person-years, with as many as 62% of these patients experiencing long-term elbow joint contracture, stiffness, and/or pain. Poor outcomes and the need for secondary surgical intervention can often be prevented nonoperatively with early or immediate active mobilization and physical therapy. However, immobilization or limited mobilization may be necessary following trauma, and it is unknown how different periods of immobilization affect pathological changes in elbow joint tissue and how these changes relate to range of motion (ROM). The purpose of this study was to investigate the effects of varying the initiation of free mobilization on elbow ROM and histological features in an animal model of elbow posttraumatic joint contracture. METHODS: Traumatic elbow dislocation was surgically induced unilaterally in rats. Injured forelimbs were immobilized in bandages for 3, 7, 14, or 21 days; free mobilization was then allowed until 42 days after injury. Post-mortem joint ROM testing and histological analysis were performed. One-way analysis of variance was used to compare ROM data between control and injured groups, and Pearson correlations were performed between ROM parameters and histological outcomes. RESULTS: Longer immobilization periods resulted in greater ROM reductions. The anterior and posterior capsule showed increases in cellularity, fibroblasts, adhesions, fibrosis, and thickness, whereas the measured outcomes in cartilage were mostly unaffected. All measured histological characteristics of the capsule were negatively correlated with ROM, indicating that higher degrees of pathology corresponded with less ROM. CONCLUSIONS: Longer immobilization periods resulted in greater ROM reductions, which correlated with worse histological outcomes in the capsule in an animal model of posttraumatic elbow contracture. The subtle differences in the timing of ROM and capsule tissue changes revealed in the present study provide new insight into the distinct timelines of biomechanical changes as well as regional tissue pathology. CLINICAL RELEVANCE: This study showed that beginning active mobilization 3 days after injury minimized posttraumatic joint contracture, thereby supporting an immediate-motion clinical treatment strategy (when possible). Furthermore, uninjured but pathologically altered periarticular tissues near the injury location may contribute to more severe contracture during longer immobilization periods as the disease state progresses.

Biomechanical Effect of Differential Tensioning on Suture-Augmented Ulnar Collateral Ligament Reconstruction of the Elbow.

BACKGROUND: Medial ulnar collateral ligament (mUCL) reconstructions are becoming increasingly prevalent among the overhand throwing population. Suture tape augmentation has the potential to provide biomechanical advantages over standard docking reconstruction. However, the optimal tensioning of the suture augmentation technique has not yet been evaluated. PURPOSE: To compare the subfailure biomechanical performance and graft strain of a standard docking mUCL reconstruction to an mUCL reconstruction using suture tape augmentation tensioned with 1 mm or 3 mm of laxity. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 18 cadaveric elbows were dissected to the mUCL anterior band and biomechanically assessed via a valgus torque protocol to failure. Elbows were randomly assigned to be reconstructed via (1) a standard docking technique, (2) a suture-augmented reconstruction with 1-mm laxity, or (3) a suture-augmented reconstruction with 3-mm laxity. Reconstructed elbows were then subjected to the same loading protocol. Subfailure mechanical properties, failure mode, and mUCL/palmaris strain were assessed. RESULTS: All reconstruction groups had decreased rotational stiffness, torque at 5° of angular rotation, and resilience compared with matched native controls. There were no differences in transition torque between groups. The failure mode of suture-augmented specimens was most often due to bone tunnel failure or reaching the maximum allowable angular displacement. In native controls or docking reconstructions, the primary failure mechanism was in the ligament or graft midsubstance. There were no significant differences in strain on the reconstructed or suture-augmented groups at any laxity compared with native controls. CONCLUSION: Suture augmentation results in similar subfailure joint biomechanical properties as the standard docking reconstruction procedure at both laxity levels in a cadaveric model. There are improvements in the failure mode of suture-augmented specimens compared with standard docking. Graft strain may be modestly reduced in the 1-mm laxity group compared with other reconstruction groups. CLINICAL RELEVANCE: Suture augmentation at both 1-mm and 3-mm laxity appears to offer similar advantages in subfailure biomechanics to standard docking reconstruction of the mUCL, with some improvements associated with failure mode. Strain data suggest a potential avoidance of graft stress shielding when tensioning the suture augmentation to 3-mm laxity, which is not as apparent with 1-mm laxity.