Discovery of active off-axis hydrothermal vents at 9° 54'N East Pacific Rise.

Comprehensive knowledge of the distribution of active hydrothermal vent fields along midocean ridges is essential to understanding global chemical and heat fluxes and endemic faunal distributions. However, current knowledge is biased by a historical preference for on-axis surveys. A scarcity of high-resolution bathymetric surveys in off-axis regions limits vent identification, which implies that the number of vents may be underestimated. Here, we present the discovery of an active, high-temperature, off-axis hydrothermal field on a fast-spreading ridge. The vent field is located 750 m east of the East Pacific Rise axis and ∼7 km north of on-axis vents at 9° 50'N, which are situated in a 50- to 100-m-wide trough. This site is currently the largest vent field known on the East Pacific Rise between 9 and 10° N. Its proximity to a normal fault suggests that hydrothermal fluid pathways are tectonically controlled. Geochemical evidence reveals deep fluid circulation to depths only 160 m above the axial magma lens. Relative to on-axis vents at 9° 50'N, these off-axis fluids attain higher temperatures and pressures. This tectonically controlled vent field may therefore exhibit greater stability in fluid composition, in contrast to more dynamic, dike-controlled, on-axis vents. The location of this site indicates that high-temperature convective circulation cells extend to greater distances off axis than previously realized. Thorough high-resolution mapping is necessary to understand the distribution, frequency, and physical controls on active off-axis vent fields so that their contribution to global heat and chemical fluxes and role in metacommunity dynamics can be determined.

In the patient's shoes: The impact of hospital proximity and volume on stage I endometrial cancer care patterns and outcomes.

OBJECTIVE: To compare the impact of travel burden and hospital volume on care patterns and outcomes in stage I endometrial cancer. METHODS: This retrospective cohort study identified patients from the National Cancer Database with stage I epithelial endometrial carcinoma who underwent hysterectomy between 2012 and 2020. Patients were categorized into: lowest quartiles of travel distance and hospital surgical volume for endometrial cancer (Local) and highest quartiles of distance and volume (Travel). Primary outcome was overall survival. Secondary outcomes were surgery route, lymph node (LN) assessment method, length of stay (LOS), 30-day readmission, and 30- and 90-day mortality. Results were stratified by tumor recurrence risk. Outcomes were compared using propensity-score matching. Propensity-adjusted survival was evaluated using Kaplan-Meier curves and compared using log-rank tests. Cox models estimated hazard ratios for death. Sensitivity analysis using modified Poisson regressions was performed. RESULTS: Among 36,514 patients, 51.4% were Local and 48.6% Travel. The two cohorts differed significantly in demographics and clinicopathologic characteristics. Upon propensity-score matching (p < 0.05 for all), more Travel patients underwent minimally invasive surgery (88.1%vs79.1%) with fewer conversions to laparotomy (2.0%vs2.6%), more sentinel (20.5%vs11.3%) and fewer traditional LN assessments (58.1vs61.7%) versus Local. Travel patients had longer intervals to surgery (≥30 days:56.7%vs50.1%) but shorter LOS (<2 days:76.9%vs59.8%), fewer readmissions (1.9%vs2.7%%), and comparable 30- and 90-day mortality. OS and HR for death remained comparable between the matched groups. CONCLUSIONS: Compared to surgery in nearby low-volume hospitals, patients with stage I epithelial endometrial cancer who travelled longer distances to high-volume centers experienced more favorable short-term outcomes and care patterns with comparable long-term survival.

Shifting trends and sicker patients: Reassessing hysterectomy performed for benign indications by gynecologic oncologists.

OBJECTIVE: To assess trends and differences in patient characteristics, complications, and distributions of hysterectomy for benign indications by benign gynecologists (BG) and gynecologic oncologists (GO). METHODS: This retrospective cohort study identified patients undergoing hysterectomy for benign indications using the National Surgical Quality Improvement Program data from 2014 to 2021. Exclusions were made for gynecologic or disseminated cancers, ascites, non-gynecologic surgeons, and cesarean hysterectomies. Primary outcome was major (≥Grade 3) 30-day complications, categorized into any complications, wound, cardiovascular and pulmonary, renal, infectious, andthromboembolic complications. Thirty-day readmissions, reoperations, and mortality were also analyzed. Propensity score matching was performed in a 1:1 match of GO to BG patients and was compared. Linear regressions assessed trends. RESULTS: Among 198,767 patients, 18% (n = 37,707) underwent hysterectomy for benign indications with GO. GO patients exhibited more risk factors for complications and differed significantly from BG patients in comorbidities and perioperative characteristics. Overall, GO patients had higher major complication rates (3.1% vs 2.2%, p < 0.001) and for several other composite complications. After matching, compared to BG, GO-performed hysterectomies had similar rates of major complications (3.0% vs 3.0%, p = 0.55) and no differences in other composite complications, except fewer reoperations (1.2 % vs 1.5%, p < 0.01) and wound complications (0.4% vs 0.5%, p = 0.02) in GO patients. Over the eight years, the percentage of GO-performed hysterectomy (ß = 0.41, R2 = 0.71,p < 0.01) increased significantly whereas BG-performed surgeries decreased by the same magnitude. BG had a significant decrease in frail patients (ß = -0.47, R2 = 0.90, p < 0.01), but GO did not (ß = -0.36, R2 = 0.38, p = 0.10). CONCLUSIONS: GO are performing more hysterectomies for benign indications on higher-risk patients. However, on a matched cohort, risks of major complications were similar between GO and BG.

The activity advantage: Objective measurement of preoperative activity is associated with postoperative recovery and outcomes in patients undergoing surgery with gynecologic oncologists.

OBJECTIVE: To examine the association between objectively-measured preoperative physical activity with postoperative outcomes and recovery milestones in patients undergoing gynecologic oncology surgeries. METHODS: Prospective cohort study of patients undergoing surgery with gynecologic oncologists who wore wearable actigraphy rings before and after surgery from 03/2021-11/2023. Exposures encompassed preoperative activity intensity (moderate- and vigorous-intensity metabolic equivalent of task-minutes [MAVI MET-mins] over seven days) and level (average daily steps over seven days). Intensity was categorized as <500, 500-1000, and >1000 MAVI MET-mins; level categorized as <8000 and ≥8000 steps/day. Primary outcome was 30-day complications. Secondary outcomes included reaching postoperative goal (≥70% of recommended preoperative intensity and level thresholds) and return to baseline (≥70% of individual preoperative intensity and level). RESULTS: Among 96 enrolled, 87 met inclusion criteria, which constituted 39% (n = 34) with <500 MET-mins and 56.3% (n = 49) with <8000 steps preoperatively. Those with <500 MET-mins and <8000 steps had higher ECOG scores (p = 0.042 & 0.037) and BMI (p = 0.049 & 0.002) vs those with higher activity; all other perioperative characteristics were similar between groups. Overall, 29.9% experienced a 30-day complication, 29.9% reached postoperative goal, and 64.4% returned to baseline. On multivariable models, higher activity was associated with lower odds of complications: 500-1000 MET-mins (OR = 0.26,95%CI = 0.07-0.92) and >1000 MET-mins (OR = 0.25,95%CI = 0.07-0.94) vs <500 MET-mins; ≥8000 steps (OR = 0.25,95%CI = 0.08-0.73) vs <8000 steps. Higher preoperative activity was associated fewer days to reach postoperative goal. CONCLUSION: Patients with high preoperative activity are associated with fewer postoperative complications and faster attainment of recovery milestones. Physical activity may be considered a modifiable risk factor for adverse postoperative outcomes.

Low serum creatinine levels are associated with major post-operative complications in patients undergoing surgery with gynecologic oncologists.

OBJECTIVE: Serum creatinine is a byproduct of muscle metabolism, and low creatinine is postulated to be associated with diminished muscle mass. This study examined the association between low pre-operative serum creatinine and post-operative outcomes. METHODS: This retrospective cohort study utilized the 2014-2021 National Surgical Quality Improvement Program to identify patients undergoing surgery with gynecologic oncologists. Patients with missing pre-operative creatinine, end-stage renal disease, sepsis, septic shock, dialysis, or pregnancy were excluded. Pre-operative creatinine was categorized into markedly low (≤0.44 mg/dL), mildly low (0.45-0.64 mg/dL), normal (0.65-0.84 mg/dL), and four categories of elevated levels (0.85-1.04, 1.05-1.24, 1.25-1.44, and ≥1.45 mg/dL). Outcomes included major (≥Grade 3) 30-day complications, categorized into any complications, wound, cardiovascular and pulmonary, renal, infectious, and thromboembolic complications. Also examined were 30-day readmissions, reoperations, and mortality. Logistic regressions assessed the association between creatinine and complications, with stratification by albumin and sensitivity analysis with propensity score matching. RESULTS: Among 84 786 patients, 0.8% had markedly low, 19.6% mildly low, and 50.2% normal creatinine; the remainder had elevated creatinine. As creatinine decreased, the risks of major complications increased in a dose-dependent manner on univariable and multivariable analyses. A total of 9.6% (n=63) markedly low patients experienced major complications, second to creatinine ≥1.45 mg/dL (9.9%, n=141). On multivariable models, both markedly and mildly low creatinine were associated with higher odds of major complications (OR 1.715, 95% CI 1.299 to 2.264 and OR 1.093, 95% CI 1.001 to 1.193) and infections (OR 1.575, 95% CI 1.118 to 2.218 and OR 1.165, 95% CI 1.048 to 1.296) versus normal. Markedly low creatinine had similar ORs to creatinine ≥1.45 mg/dL and was further associated with higher odds of cardiovascular and pulmonary complications (OR 2.301, 95% CI 1.300 to 4.071), readmissions (OR 1.403, 95% CI 1.045 to 1.884), and mortality (OR 2.718, 95% CI 1.050 to 7.031). After albumin stratification, associations persisted for markedly low creatinine. Propensity-weighted analyses demonstrated congruent findings. CONCLUSIONS: Low creatinine levels are associated with major post-operative complications in gynecologic oncology in a dose-dependent manner. Low creatinine can offer useful information for pre-operative risk stratification, surgical counseling, and peri-operative management.

Retinoids in the treatment of photoageing: A histological study of topical retinoid efficacy in black skin.

BACKGROUND: Photoageing describes complex cutaneous changes that occur due to chronic exposure to solar ultraviolet radiation (UVR). The 'gold standard' for the treatment of photoaged white skin is all-trans retinoic acid (ATRA); however, cosmetic retinol (ROL) has also proven efficacious. Recent work has identified that black skin is susceptible to photoageing, characterized by disintegration of fibrillin-rich microfibrils (FRMs) at the dermal-epidermal junction (DEJ). However, the impact of topical retinoids for repair of black skin has not been well investigated. OBJECTIVES: To determine the potential of retinoids to repair photoaged black skin. METHODS: An exploratory intervention study was performed using an in vivo, short-term patch test protocol. Healthy but photoaged black volunteers (>45 years) were recruited to the study, and participant extensor forearms were occluded with either 0.025% ATRA (n = 6; 4-day application due to irritancy) or ROL (12-day treatment protocol for a cosmetic) at concentrations of 0.3% (n = 6) or 1% (n = 6). Punch biopsies from occluded but untreated control sites and retinoid-treated sites were processed for histological analyses of epidermal characteristics, melanin distribution and dermal remodelling. RESULTS: Treatment with ATRA and ROL induced significant acanthosis (all p < 0.001) accompanied by a significant increase in keratinocyte proliferation (Ki67; all p < 0.01), dispersal of epidermal melanin and restoration of the FRMs at the DEJ (all p < 0.01), compared to untreated control. CONCLUSIONS: This study confirms that topical ATRA has utility for the repair of photoaged black skin and that ROL induces comparable effects on epidermal and dermal remodelling, albeit over a longer timeframe. The effects of topical retinoids on black photoaged skin are similar to those reported for white photoaged skin and suggest conserved biology in relation to repair of UVR-induced damage. Further investigation of topical retinoid efficacy in daily use is warranted for black skin.

Sport-related concussions in baseball and softball: do mechanisms of injury affect recovery?

OBJECTIVE: Baseball and softball pose unique risks for sport-related concussion (SRC). Although these are not collision sports, concussions in baseball and softball can nonetheless involve high-speed impacts. In a regional, single-institution cohort of baseball and softball athletes who sustained an SRC, the current study sought to 1) describe the mechanisms of injury that led to SRC, and 2) compare initial symptom burden and recovery metrics across mechanisms, including time to return to learn (RTL), time to symptom resolution, and time to return to play (RTP) by mechanism of injury. METHODS: A retrospective cohort study was performed of baseball and softball athletes 12 to 23 years old who sustained an SRC between November 2017 and April 2022. Mechanisms of injury were divided into two categories: 1) contact mechanism (i.e., what initiated contact with the injured player, such as head-to-ball), and 2) player mechanism (i.e., the action the injured player was performing at the time of injury, such as fielding). The recovery outcomes of time to RTL, symptom resolution, and RTP were compared between mechanisms using bivariate analysis and multivariable regression analysis, controlling for sex, age, time to present to concussion clinic, and initial total symptom score. RESULTS: The sample included 58 baseball and softball players (60.3% female, mean age 16.0 ± 1.9 years). Most SRCs (62.1%) occurred during competition. Head-to-ball (50.0%) was the most common contact mechanism, followed by head-to-head/body (31.0%) and head-to-wall/ground/equipment (17.2%). Fielding (63.8%) was the most common player mechanism, followed by drills (20.7%) and running (13.8%). SRCs sustained in practice had significantly longer RTL (median 10.0 [interquartile range (IQR) 3.3-16.3] vs 4.0 [IQR 2.0-8.0] days; U = 421.5, p = 0.031) and symptom resolution (37.0 [IQR 18.0-90.0] vs 14.0 [IQR 7.0-41.0] days; U = 406.5, p = 0.025) compared with SRCs sustained in competition. Multivariable regression analysis revealed that head-to-wall/ground/equipment contact mechanism was associated with longer RTL (ß = 0.30, 95% CI 0.07-0.54, p = 0.013). CONCLUSIONS: The current study found that SRCs in baseball and softball occurred more often in competition than in practice. Head-to-ball and fielding were the most common contact and player mechanisms, respectively. SRCs sustained in practice were associated with longer time to RTL and symptom resolution, and head-to-wall/ground/equipment was associated with longer RTL in multivariable regression analysis. These results provide empirical data to improve concussion safety in baseball/softball.

Loss of Fgfr1 and Fgfr2 in Scleraxis-lineage cells leads to enlarged bone eminences and attachment cell death.

BACKGROUND: Tendons and ligaments attach to bone are essential for joint mobility and stability in vertebrates. Tendon and ligament attachments (ie, entheses) are found at bony protrusions (ie, eminences), and the shape and size of these protrusions depend on both mechanical forces and cellular cues during growth. Tendon eminences also contribute to mechanical leverage for skeletal muscle. Fibroblast growth factor receptor (FGFR) signaling plays a critical role in bone development, and Fgfr1 and Fgfr2 are highly expressed in the perichondrium and periosteum of bone where entheses can be found. RESULTS AND CONCLUSIONS: We used transgenic mice for combinatorial knockout of Fgfr1 and/or Fgfr2 in tendon/attachment progenitors (ScxCre) and measured eminence size and shape. Conditional deletion of both, but not individual, Fgfr1 and Fgfr2 in Scx progenitors led to enlarged eminences in the postnatal skeleton and shortening of long bones. In addition, Fgfr1/Fgfr2 double conditional knockout mice had more variation collagen fibril size in tendon, decreased tibial slope, and increased cell death at ligament attachments. These findings identify a role for FGFR signaling in regulating growth and maintenance of tendon/ligament attachments and the size and shape of bony eminences.

Mouse Pancreatic Peptide Hormones Probed at the Sub-Single-Islet Level: The Effects of Acute Corticosterone Treatment.

We combine liquid chromatography coupled with ion mobility spectrometry-mass spectrometry to elucidate how short exposure to corticosterone (Cort) alters the output of mouse pancreatic islet hormones. The workflow enables the robust separation of mouse insulin 1 (Ins1) and insulin 2 (Ins2) and the detection of major islet hormones in a homogenate equivalent to 100-150 islet cells. We show that Ins2 has a unique structure and is degraded much faster than Ins1. Further investigation indicates that Ins2 may populate both T and R states, whereas Ins1 may not. The assemblies of Ins1's B-chain also introduce more structural heterogeneity than Ins2. Collectively, these features account for their unique degradation profiles, the diabetes risk associated with Ins1, and the protective effect of Ins2. In the same experiments, we observe that the ratio of amylin to Ins1 increased significantly in Cort-treated mice (15:1) compared to the control mice (42:1), correlating well with ß-cell proliferation observed in immunoassays on the same animal model. We observe no increase in intact full-length insulin levels but more of the truncated forms, indicating that enzymatic activity is accelerated. Our data provide a molecular basis for reduced insulin action induced by Cort and connections between insulin turnover and insulin resistance.

Counting Electrons in Electrides.

The selection and design of charge integration methods remain an outstanding challenge in materials chemistry. In complex materials like electrides, this challenge is amplified by the small charge and complex shape of electride wave functions. For these reasons, popular integration methods, such as the Bader method, usually fail to assign any charge to the bare electrons in an electride. To address this challenge, we developed an algorithm that instead partitions the charge based on the electron localization function (ELF), a popular scheme for visualizing chemically important features in molecules and solids. The algorithm uses Bader segmentation of the ELF to find the electride electrons and Voronoi segmentation of the ELF to identify atoms. We apply this method, "BadELF", to the quantification of atomic radii and oxidation states in both ionic compounds and electrides. For ionic compounds, we find that the BadELF method yields radii that agree closely with Shannon crystal radii, while the oxidation states agree closely with the Bader method. When they are applied to electrides, however, only the BadELF algorithm yields chemically meaningful charges. We argue that the BadELF method provides a useful strategy to identify electrides and obtain new insight into their most essential property: the quantity of electrons within them.

Mechanics and differential healing outcomes of small and large defect injuries of the tendon-bone attachment in the rat rotator cuff.

INTRODUCTION: Rotator cuff tear size affects clinical outcomes following rotator cuff repair and is correlated with the risk of recurrent tendon defects. This study aimed to understand if and how the initial defect size influences the structural and mechanical outcomes of the injured rotator cuff attachment in vivo. METHODS: Full-thickness punch injuries of the infraspinatus tendon-bone attachment in Long Evans rats were created to compare differences in healing outcomes between small and large defects. Biomechanical properties, gross morphology, bone remodeling, and cell and tissue morphology were assessed at both 3- and 8-weeks of healing. RESULTS: At the time of injury (no healing), large defects had decreased mechanical properties compared to small defects, and both defect sizes had decreased mechanical properties compared to intact attachments. However, the mechanical properties of the two defect groups were not significantly different from each other after 8-weeks of healing and significantly improved compared to no healing but failed to return to intact levels. Local bone volume at the defect site was higher in large compared to small defects on average and increased from 3- to 8-weeks. In contrast, bone quality decreased from 3- to 8-weeks of healing and these changes were not dependent on defect size. Qualitatively, large defects had increased collagen disorganization and neovascularization compared to small defects. DISCUSSION: In this study, we showed that both large and small defects did not regenerate the mechanical and structural integrity of the intact rat rotator cuff attachment following healing in vivo after 8 weeks of healing.

Biological Consequences of Vanadium Effects on Formation of Reactive Oxygen Species and Lipid Peroxidation.

Lipid peroxidation (LPO), a process that affects human health, can be induced by exposure to vanadium salts and compounds. LPO is often exacerbated by oxidation stress, with some forms of vanadium providing protective effects. The LPO reaction involves the oxidation of the alkene bonds, primarily in polyunsaturated fatty acids, in a chain reaction to form radical and reactive oxygen species (ROS). LPO reactions typically affect cellular membranes through direct effects on membrane structure and function as well as impacting other cellular functions due to increases in ROS. Although LPO effects on mitochondrial function have been studied in detail, other cellular components and organelles are affected. Because vanadium salts and complexes can induce ROS formation both directly and indirectly, the study of LPO arising from increased ROS should include investigations of both processes. This is made more challenging by the range of vanadium species that exist under physiological conditions and the diverse effects of these species. Thus, complex vanadium chemistry requires speciation studies of vanadium to evaluate the direct and indirect effects of the various species that are present during vanadium exposure. Undoubtedly, speciation is important in assessing how vanadium exerts effects in biological systems and is likely the underlying cause for some of the beneficial effects reported in cancerous, diabetic, neurodegenerative conditions and other diseased tissues impacted by LPO processes. Speciation of vanadium, together with investigations of ROS and LPO, should be considered in future biological studies evaluating vanadium effects on the formation of ROS and on LPO in cells, tissues, and organisms as discussed in this review.

Risk Stratification for Oropharyngeal Squamous Cell Carcinoma Using Texture Analysis on CT - A Step Beyond HPV Status.

Background and Purpose: Human papillomavirus-associated oropharyngeal squamous cell carcinoma (OPSCC) is increasingly prevalent. Despite the overall more favorable outcome, the observed heterogeneous treatment response within this patient group highlights the need for additional means to prognosticate and guide clinical decision-making. Promising prediction models using radiomics from primary OPSCC have been derived. However, no model/s using metastatic lymphadenopathy exist to allow prognostication in those instances when the primary tumor is not seen. The aim of our study was to evaluate whether radiomics using metastatic lymphadenopathy allows for the development of a useful risk assessment model comparable to the primary tumor and whether additional knowledge of the HPV status further improves its prognostic efficacy. Materials and Methods: 80 consecutive patients diagnosed with stage III-IV OPSCC between February 2009 and October 2015, known human papillomavirus status, and pre-treatment CT images were retrospectively identified. Manual segmentation of primary tumor and metastatic lymphadenopathy was performed and the extracted texture features were used to develop multivariate assessment models to prognosticate treatment response. Results: Texture analysis of either the primary or metastatic lymphadenopathy from pre-treatment enhanced CT images can be used to develop models for the stratification of treatment outcomes in OPSCC patients. AUCs range from .78 to .85 for the various OPSCC groups tested, indicating high predictive capability of the models. Conclusions: This preliminary study can form the basis multi-centre trial that may help optimize treatment and improve quality of life in patients with OPSCC in the era of personalized medicine.

Mechanical and oral antibiotic bowel preparation in ovarian cancer debulking: Are we lowering or just trading surgical complications?

OBJECTIVES: To examine postoperative complications associated with preoperative mechanical and oral antibiotic bowel preparation (MOABP) for patients with ovarian cancer who underwent bowel resection at cytoreductive surgery (CRS). METHODS: This was a single-institution retrospective study of patients with ovarian cancer undergoing CRS from 01/2011-12/2020 using ICD-10 diagnoses and procedure codes. Patients were stratified by those who underwent bowel resection versus no resection. Bowel resection patients were further stratified by those who underwent MOABP versus no bowel preparation. Patient demographics, tumor data, and perioperative metrics were collected. Unadjusted and adjusted logistic regression evaluated odds of 30-day postoperative complications in patients with bowel resection versus no resection and those with MOABP versus no bowel preparation. RESULTS: Of 919 patients identified, 215 (23.3%) required bowel resection, which included 81 (37.7%) who received MOABP. Patient characteristics, co-morbidities, and cancer data were similar between MOABP versus no bowel preparation patients. MOABP patients underwent more interval CRS (34.6% versus 9.0%), more optimal surgical resections (96.3% versus 83.8%), fewer diverting ostomies (13.5% versus 33.5%), and shorter hospital stays (7.1 versus 9.4 days) than no bowel preparation patients. On adjusted analyses, MOABP patients experienced significantly lower odds of deep/organ-space surgical infections and 30-day readmissions but higher odds of unplanned intensive care unit (ICU) admissions and grade 3 or higher cardiac and gastrointestinal complications. CONCLUSIONS: Patients who underwent preoperative MOABP prior to ovarian cancer CRS with bowel resection had lower odds or deep/organ-space infections and readmissions, shorter hospital stays, fewer diverting ostomies, and more optimal resections. However, these patients also experienced higher odds of ICU admissions and grade 3 or higher cardiac and gastrointestinal complications. The positive and negative postoperative outcomes in this population should be considered in clinical practice.

Theranostic Copolymers Neutralize Reactive Oxygen Species and Lipid Peroxidation Products for the Combined Treatment of Traumatic Brain Injury.

Traumatic brain injury (TBI) results in the generation of reactive oxygen species (ROS) and lipid peroxidation product (LPOx), including acrolein and 4-hydroxynonenal (4HNE). The presence of these biochemical derangements results in neurodegeneration during the secondary phase of the injury. The ability to rapidly neutralize multiple species could significantly improve outcomes for TBI patients. However, the difficulty in creating therapies that target multiple biochemical derangements simultaneously has greatly limited therapeutic efficacy. Therefore, our goal was to design a material that could rapidly bind and neutralize both ROS and LPOx following TBI. To do this, a series of thiol-functionalized biocompatible copolymers based on lipoic acid methacrylate and polyethylene glycol monomethyl ether methacrylate (FW ∼ 950 Da) (O950) were prepared. A polymerizable gadolinium-DOTA methacrylate monomer (Gd-MA) was also synthesized starting from cyclen to facilitate direct magnetic resonance imaging and in vivo tracking of accumulation. These neuroprotective copolymers (NPCs) were shown to rapidly and effectively neutralize both ROS and LPOx. Horseradish peroxidase absorbance assays showed that the NPCs efficiently neutralized H2O2, while R-phycoerythrin protection assays demonstrated their ability to protect the fluorescent protein from oxidative damage. 1H NMR studies indicated that the thiol-functional NPCs rapidly form covalent bonds with acrolein, efficiently removing it from solution. In vitro cell studies with SH-SY5Y-differentiated neurons showed that NPCs provide unique protection against toxic concentrations of both H2O2 and acrolein. NPCs rapidly accumulate and are retained in the injured brain in controlled cortical impact mice and reduce post-traumatic oxidative stress. Therefore, these materials show promise for improved target engagement of multiple biochemical derangements in hopes of improving TBI therapeutic outcomes.

Chemoselective, osmium-free, dihydroxylation/oxidative cleavage of heteroaryl isoprenes by a contemporary Malaprade reaction.

The methyl ketone is a central synthetic building block for the construction of advanced heteroaryl scaffolds and systems. Reactions, including oxidative cyclization strategies, are often predicated on efficient access to this ubiquitous moiety. In the context of arenes, standard approaches leveraging Markovnikov hydration/oxidation or oxidative cleavage of the C-C π bond often afford satisfactory performance. However, when the substrate contains an electron-deficient heteroaryl core, the traditional Malaprade reaction, and related oxidative-cleavage strategies, frequently result in diminished performance over carbon-based arenes. In this work we present the development and application of an oxidative cleavage reaction of various pyridinyl isoprenes towards accessing the downstream methyl ketone for utilization in advanced cyclizations for the preparation of soft-N-donor complexant scaffolds. This efficient protocol parallels the principles of Green chemistry by exchanging KMnO4 for the toxic OsO4 and offers the end-user an efficient, more environmentally friendly option for accessing heteroaryl methyl ketones in one hour of reaction time using potassium permanganate and sodium paraperiodate as a synergistically potent oxidative cleavage system. The wide substrate scope defined access to simple, as well as advanced heteroaryl methyl ketones. Method development, optimization, substrate scope, preliminary mechanistic observations, and a scale up reaction are delineated herein.

A qualitative analysis of online misinformation and conspiracy theories in psoriasis.

Psoriasis is a chronic, hereditary disease with a complex immunopathogenesis, rendering it susceptible to misinformation. Misinformation related to psoriasis can have negative effects both on the public perception of psoriasis and on patients' knowledge of psoriasis. To characterize misinformation related to psoriasis available online, we performed a formal literature review via PubMed and a thematic review via Google. Key themes of misinformation included 'victim-blaming' (hygiene), 'vector' (contagion), 'vaccination', 'vilification' of conventional therapy, 'validation' of natural treatment and diet, 'veneration' of cures and 'vocalization' from celebrities. Misinformation related to psoriasis is pervasive on social media and other websites. Dermatologists, as patient advocates, should be aware of the content of misinformation available online and combat misleading health information to optimize health outcomes for patients with psoriasis.

Confidence of Irish dermatologists in caring for patients with skin of colour.

To assess Irish dermatologists' confidence with dermatology in patients with skin of colour (SOC), an online survey was distributed to all members of the Irish Association of Dermatology (IAD) by email. Half (50%) of respondents were 'not confident' or 'not at all confident' in diagnosing skin conditions and one-third (33.9%) were 'not confident' or 'not at all confident' in managing skin conditions in patients with SOC. Irish dermatologists have low confidence with skin pathology in SOC, and specific training could reduce this disparity.

PAPA-like syndrome with heterozygous mutation in the MEFV gene.

A patient presented with a history of recurrent pyoderma gangrenosum, arthritis and extensive acne, prompting a genetic workup for PAPA syndrome. An MEFV mutation was identified and a change in therapeutic strategy from anakinra to colchicine was successful. Click https://www.wileyhealthlearning.com/#/online-courses/b52447c0-1d37-472d-b0c0-7817352d6f68 for the corresponding questions to this CME article.

The COV-ED Survey: exploring the impact of learning and teaching from home on parent/carers' and teachers' mental health and wellbeing during COVID-19 lockdown.

BACKGROUND: Following the emergence of COVID-19 in the UK, on March 18th 2020 the majority of schools in England closed and families and teachers were tasked with providing educational support for children and adolescents within the home environment. Little is known, however, regarding the impact of remote teaching and learning on the mental wellbeing of parents/carers and teaching staff. METHODS: The Coronavirus Education (COV-ED) online survey explored the practicalities of learning and teaching from home for 329 parents/carers and 117 teachers of 11-15 year old adolescents in England, during June/July 2020, and the associated impact on their mental wellbeing. Participants were recruited through schools and via University of Warwick social media channels. Data was analysed using a series of Multiple Linear and Multivariate Regressions. RESULTS: Despite coping well with the challenges of remote learning, a third of teachers reported below average mental wellbeing on the Warwick-Edinburgh Mental Wellbeing Scale. Multivariate regression revealed that wellbeing was associated with access to resources and confidence to teach from home. Almost half of parents/carers surveyed reported below average wellbeing. Multivariate regression revealed that poor wellbeing was more common in those who were also working from home and who lacked support for their own mental health. Concerns about their child's mental health and lack of access to electronic devices and workspace were also significantly associated with the mental wellbeing of parents/carers. CONCLUSIONS: Whilst young people's mental health and wellbeing has, and continues to be a national priority, the mental health and wellbeing of the families and teachers supporting them has not previously been explored. Our survey population was of predominantly white British heritage, female and living in the West Midlands UK, therefore, findings should be treated with caution. Findings provide a snapshot of factors that may be of significance to families and schools in supporting the mental wellbeing of those tasked with learning from home. They will help i) increase knowledge and awareness with regard to future support of families and teachers during similar crises; ii) enable the design and development of practical solutions in the delivery of remote teaching and learning; and, iii) help address the mental wellbeing needs of those tasked with supporting adolescents.