Cycloadditions of Diazoalkenes with P4 and tBuCP: Access to Diazaphospholes.

Diazoalkenes readily react with tert­butylphosphaalkyne (tBuCP) and white phosphorus (P4) to afford novel phosphorus heterocycles, 3H­1,2,4-diazamonophospholes and 1,2,3,4-diazadiphospholes. Both species represent rare examples of neutral heterophospholes. The mechanism of formation and the electronic structures of these formal (3+2) cycloaddition products were analyzed computationally. The new phospholes form structurally diverse coordination compounds with transition metal and main group elements. Given the growing number of stable diazoalkenes, this work offers a straightforward route to neutral aza(di-)phospholes as a new ligand class.

para-Aminoazobenzenes - Bipolar Redox-Active Molecules.

Azobenzenes (ABs) are versatile compounds featured in numerous applications for energy storage systems, such as solar thermal storages or phase change materials. Additionally, the reversible one-electron reduction of these diazenes to the nitrogen-based anion radical has been used in battery applications. Although the oxidation of ABs is normally irreversible, 4,4'-diamino substitution allows a reversible 2e- oxidation, which is attributed to the formation of a stable bis-quinoidal structure. Herein, we present a system that shows a bipolar redox behaviour. In this way, ABs can serve not only as anolytes, but also as catholytes. The resulting redox potentials can be tailored by suitable amine- and ring-substitution. For the first time, the solid-state structure of the oxidized form could be characterized by X-ray diffraction.

House Sparrows as Sentinels of Childhood Lead Exposure.

Our understanding of connections between human and animal health has advanced substantially since the canary was introduced as a sentinel of toxic conditions in coal mines. Nonetheless, the development of wildlife sentinels for monitoring human exposure to toxins has been limited. Here, we capitalized on a three-decade long child blood lead monitoring program to demonstrate that the globally ubiquitous and human commensal house sparrow (Passer domesticus) can be used as a sentinel of human health risks in urban environments impacted by lead mining. We showed that sparrows are a viable proxy for the measurement of blood lead levels in children at a neighborhood scale (0.28 km2). In support of the generalizability of this approach, the blood lead relationship established in our focal mining city enabled us to accurately predict elevated blood lead levels in children from another mining city using only sparrows from the second location. Using lead concentrations and lead isotopic compositions from environmental and biological matrices, we identified shared sources and pathways of lead exposure in sparrows and children, with strong links to contamination from local mining emissions. Our findings showed how human commensal species can be used to identify and predict human health risks over time and space.

Microbial Sulfur and Arsenic Oxidation Facilitate the Establishment of Biocrusts during Reclamation of Degraded Mine Tailings.

Degraded tailings generated by the mining of metal ores are major environmental threats to the surrounding ecosystems. Tailing reclamation, however, is often impeded due to adverse environmental conditions, with depleted key nutrients (i.e., nitrogen (N) and phosphorus (P)) and elevated sulfur and metal(loid) concentrations. Formation of biocrusts may significantly accelerate nutrient accumulation and is therefore an essential stage for tailing reclamation. Although suggested to play an important role, the microbial community composition and key metabolisms in biocrusts remain largely unknown and are therefore investigated in the current study. The results suggested that sulfur and arsenic oxidation are potential energy sources utilized by members of predominant biocrust bacterial families, including Beijerinckiaceae, Burkholderiaceae, Hyphomicrobiaceae, and Rhizobiaceae. Accordingly, the S and As oxidation potentials are elevated in biocrusts compared to those in their adjacent tailings. Biocrust growth, as proxied by chlorophyll concentrations, is enhanced in treatments supplemented with S and As. The elevated biocrust growth might benefit from nutrient acquisition services (i.e., nitrogen fixation and phosphorus solubilization) fueled by microbial sulfur and arsenic oxidation. The current study suggests that sulfur- and arsenic-oxidizing microorganisms may play important ecological roles in promoting biocrust formation and facilitating tailing reclamation.

One-year effectiveness of long-term exercise therapy in people with axial spondyloarthritis and severe functional limitations.

OBJECTIVE: To evaluate the effectiveness of long-term, personalized, supervised exercise therapy on functional ability compared with usual care in people with axial spondyloarthritis (axSpA) and severe functional limitations. METHODS: Participants were randomly 1:1 assigned to the intervention(maximal 64 sessions, with 14 additional optional sessions of supervised active exercise therapy(e.g. aerobic and muscle strengthening) with individualized goal-setting, education and self-management regarding physical activity) or usual care(care determined by clinician(s) and participants themselves). Primary end point was the change in the Patient-Specific Complaints activity ranked 1 (PSC1 (0-10)) at 52 weeks. Secondary endpoints were the PSC activities ranked 2 and 3, the Bath Ankylosing Spondylitis Functional Index, 6-min walk test, Patient Reported Outcome Measurement Information System-Physical Function-10 and the Short Form-36 Physical and Mental Component Summary Score (SF-36 PCS and MCS). Statistical comparisons comprised independent student t-tests and linear mixed models, based on intention-to-treat. RESULTS: 214 participants(49% female, age 52 (SD 12) years), were randomized to the intervention (n = 110) or usual care (N = 104) group. In the intervention group 93% started treatment, using on average 40.5 sessions (SD 15.1). At 52 weeks, the difference in change in PSC1 between groups favored the intervention group (mean difference [95% CI]; -1.8 [-2.4 to -1.2]). additionally, all secondary outcomes, except the SF-36 MSC, showed significantly greater improvements in the intervention group with effect sizes ranging from 0.4-0.7. CONCLUSION: Long-term, supervised exercise therapy proved more effective than usual care in improving functional disability and physical quality of life in people with axSpA and severe functional limitations. CLINICAL TRIAL REGISTER NUMBER: Netherlands Trial Register NL8238, included in the International Clinical Trial Registry Platform (ICTRP) (https://trialsearch.who.int/Trial2.aspx?TrialID=NL8238).

Microbially mediated sulfur oxidation coupled with arsenate reduction within oligotrophic mining-impacted habitats.

Arsenate reduction is a major cause of As release from soils which threatens more than 200 million people worldwide. While heterotrophic As(V) reduction has been investigated extensively, the mechanism of chemolithotrophic As(V) reduction is less studied. Since As is frequently found as sulfidic minerals in the environment, microbial mediated sulfur oxidation coupled to As(V) reduction (SOAsR), a chemolithotrophic process, may be more favorable in oligotrophic mining-impacted sites (e.g., As-contaminated mine tailings). While SOAsR is thermodynamically favorable, knowledge regarding this biogeochemical process is still limited. The current study suggested that SOAsR was a more prevalent process compared to heterotrophic As(V) reduction in oligotrophic sites, such as mine tailings. The water-soluble reduced sulfur concentration was predicted as one of the major geochemical parameters that substantially impacted SOAsR potentials. A combination of DNA-SIP and metagenome binning revealed members of the genera Sulfuricella, Ramlibacter, and Sulfuritalea as sulfur oxidizing As(V)-reducing bacteria (SOAsRB) in mine tailings. Genome mining further expanded the list of potential SOAsRBs to diverse phylogenetic lineages such as members associated with Burkholderiaceae and Rhodocyclaceae. Metagenome analysis using multiple tailing samples across southern China confirmed that the putative SOAsRB were the dominant As(V) reducers in these sites. Together, the current findings expand our knowledge regarding the chemolithotrophic As(V) reduction process, which may be harnessed to facilitate future remediation practices in mine tailings.

Genome analysis and description of Tunturibacter gen. nov. expands the diversity of Terriglobia in tundra soils.

Increased temperatures in Arctic tundra ecosystems are leading to higher microbial respiration rates of soil organic matter, resulting in the release of carbon dioxide and methane. To understand the effects of this microbial activity, it is important to better characterize the diverse microbial communities in Arctic soil. Our goal is to refine our understanding of the phylogenetic diversity of Terriglobia, a common but elusive group within the Acidobacteriota phylum. This will help us link this diversity to variations in carbon and nitrogen usage patterns. We used long-read Oxford Nanopore MinION sequences in combination with metagenomic short-read sequences to assemble complete Acidobacteriota genomes. This allowed us to build multi-locus phylogenies and annotate pangenome markers to distinguish Acidobacteriota strains from several tundra soil isolates. We identified a phylogenetic cluster containing four new species previously associated with Edaphobacter lichenicola. We conclude that this cluster represents a new genus, which we have named Tunturibacter. We describe four new species: Tunturibacter lichenicola comb. nov., Tunturibacter empetritectus sp. nov., Tunturibacter gelidoferens sp. nov., and Tunturibacter psychrotolerans sp. nov. By uncovering new species and strains within the Terriglobia and improving the accuracy of their phylogenetic placements, we hope to enhance our understanding of this complex phylum and shed light on the mechanisms that shape microbial communities in polar soils.

Blood lead increases and haemoglobin decreases in urban birds along a soil contamination gradient in a mining city.

Lead contaminated soil is a persistent global threat to the health of animal populations. Nevertheless, links between soil lead and its adverse effects on exposed wildlife remain poorly understood. Here, we explore local geographic patterns of exposure in urban birds along a gradient of lead contamination in Broken Hill, an Australian mining city. Soil lead concentrations are linked to co-located blood lead measurements in rock pigeons (Columba livia), house sparrows (Passer domesticus), crested pigeons (Ocyphaps lophotes) and white-plumed honeyeaters (Lichenostomus ornatus). Median blood lead levels were highest in crested pigeons (59.6 µg/dL), followed by house sparrows (35.2 µg/dL), rock pigeons (35.1 µg/dL), and white-plumed honeyeaters (27.4 µg/dL). Blood lead levels in all species declined away from mining areas, the primary source of lead contamination in Broken Hill. Blood lead increased significantly and at the greatest rate relative to soil lead in the three ground foraging species (crested pigeons, house sparrows, rock pigeons). For these species, soil lead concentrations below 200 mg/kg and 900 mg/kg were needed to maintain a median blood lead concentration under the lower threshold of the subtoxic (20-50 µg/dL) and toxic (≥50 µg/dL) effect ranges previously identified for some bird species. We also investigated the effects of lead exposure on blood haemoglobin levels as a general measure of physiological condition in birds exposed to different levels of soil lead contamination. Overall, for every 1 µg/dL increase in blood lead, haemoglobin decreased by 0.11 g/L. The rate of this decrease was not significantly different between species, which supports the measurement of haemoglobin as a consistent though insensitive measure of physiological condition in chronically lead exposed birds. Our findings reflect the importance of lead contaminated soil as a widespread source of elevated blood lead and supressed haemoglobin levels in birds inhabiting urbanised and mining impacted environments.

Measuring transformative virtual reality experiences in children's drawings.

Transformative experiences in an individual's life have a lasting impact on identity, belief system, and values. At the core of these experiences is the complex emotion of awe that promotes learning, making it worthwhile to study from an educational point of view. Drawing studies may provide a useful measure of awe in children-one that is more intuitive and attractive than questionnaires alone. Previous studies conducted with adults indicated that the diminished self, associated with transformative experiences, manifests in an actual decrease in size for figures representing the self in drawings. In the current study, self-representation was investigated in drawings of 10- to 12-year-old primary school children within the context of an immersive virtual reality (VR) experience that elicits the overview effect, known to lead to an intense apperception of awe. We did not replicate the adult findings regarding self-size in this younger age group. However, details and complexity in children's drawings appeared to be impacted by the awe-elicitation procedure in VR. These elements subsequently correlated to learning gains instead of the overview effect, indicating that this measure could be linked to cognitive ability. The findings of the current study contribute to a better understanding of how drawings reflect self-transcendental experiences; however, they also reveal that in younger age groups, they are not necessarily reflected in decreased self-size.

A concept for international societally relevant microbiology education and microbiology knowledge promulgation in society.

EXECUTIVE SUMMARY: Microbes are all pervasive in their distribution and influence on the functioning and well-being of humans, life in general and the planet. Microbially-based technologies contribute hugely to the supply of important goods and services we depend upon, such as the provision of food, medicines and clean water. They also offer mechanisms and strategies to mitigate and solve a wide range of problems and crises facing humanity at all levels, including those encapsulated in the sustainable development goals (SDGs) formulated by the United Nations. For example, microbial technologies can contribute in multiple ways to decarbonisation and hence confronting global warming, provide sanitation and clean water to the billions of people lacking them, improve soil fertility and hence food production and develop vaccines and other medicines to reduce and in some cases eliminate deadly infections. They are the foundation of biotechnology, an increasingly important and growing business sector and source of employment, and the centre of the bioeconomy, Green Deal, etc. But, because microbes are largely invisible, they are not familiar to most people, so opportunities they offer to effectively prevent and solve problems are often missed by decision-makers, with the negative consequences this entrains. To correct this lack of vital knowledge, the International Microbiology Literacy Initiative-the IMiLI-is recruiting from the global microbiology community and making freely available, teaching resources for a curriculum in societally relevant microbiology that can be used at all levels of learning. Its goal is the development of a society that is literate in relevant microbiology and, as a consequence, able to take full advantage of the potential of microbes and minimise the consequences of their negative activities. In addition to teaching about microbes, almost every lesson discusses the influence they have on sustainability and the SDGs and their ability to solve pressing problems of societal inequalities. The curriculum thus teaches about sustainability, societal needs and global citizenship. The lessons also reveal the impacts microbes and their activities have on our daily lives at the personal, family, community, national and global levels and their relevance for decisions at all levels. And, because effective, evidence-based decisions require not only relevant information but also critical and systems thinking, the resources also teach about these key generic aspects of deliberation. The IMiLI teaching resources are learner-centric, not academic microbiology-centric and deal with the microbiology of everyday issues. These span topics as diverse as owning and caring for a companion animal, the vast range of everyday foods that are produced via microbial processes, impressive geological formations created by microbes, childhood illnesses and how they are managed and how to reduce waste and pollution. They also leverage the exceptional excitement of exploration and discovery that typifies much progress in microbiology to capture the interest, inspire and motivate educators and learners alike. The IMiLI is establishing Regional Centres to translate the teaching resources into regional languages and adapt them to regional cultures, and to promote their use and assist educators employing them. Two of these are now operational. The Regional Centres constitute the interface between resource creators and educators-learners. As such, they will collect and analyse feedback from the end-users and transmit this to the resource creators so that teaching materials can be improved and refined, and new resources added in response to demand: educators and learners will thereby be directly involved in evolution of the teaching resources. The interactions between educators-learners and resource creators mediated by the Regional Centres will establish dynamic and synergistic relationships-a global societally relevant microbiology education ecosystem-in which creators also become learners, teaching resources are optimised and all players/stakeholders are empowered and their motivation increased. The IMiLI concept thus embraces the principle of teaching societally relevant microbiology embedded in the wider context of societal, biosphere and planetary needs, inequalities, the range of crises that confront us and the need for improved decisioning, which should ultimately lead to better citizenship and a humanity that is more sustainable and resilient. ABSTRACT: The biosphere of planet Earth is a microbial world: a vast reactor of countless microbially driven chemical transformations and energy transfers that push and pull many planetary geochemical processes, including the cycling of the elements of life, mitigate or amplify climate change (e.g., Nature Reviews Microbiology, 2019, 17, 569) and impact the well-being and activities of all organisms, including humans. Microbes are both our ancestors and creators of the planetary chemistry that allowed us to evolve (e.g., Life's engines: How microbes made earth habitable, 2023). To understand how the biosphere functions, how humans can influence its development and live more sustainably with the other organisms sharing it, we need to understand the microbes. In a recent editorial (Environmental Microbiology, 2019, 21, 1513), we advocated for improved microbiology literacy in society. Our concept of microbiology literacy is not based on knowledge of the academic subject of microbiology, with its multitude of component topics, plus the growing number of additional topics from other disciplines that become vitally important elements of current microbiology. Rather it is focused on microbial activities that impact us-individuals/communities/nations/the human world-and the biosphere and that are key to reaching informed decisions on a multitude of issues that regularly confront us, ranging from personal issues to crises of global importance. In other words, it is knowledge and understanding essential for adulthood and the transition to it, knowledge and understanding that must be acquired early in life in school. The 2019 Editorial marked the launch of the International Microbiology Literacy Initiative, the IMiLI. HERE, WE PRESENT: our concept of how microbiology literacy may be achieved and the rationale underpinning it; the type of teaching resources being created to realise the concept and the framing of microbial activities treated in these resources in the context of sustainability, societal needs and responsibilities and decision-making; and the key role of Regional Centres that will translate the teaching resources into local languages, adapt them according to local cultural needs, interface with regional educators and develop and serve as hubs of microbiology literacy education networks. The topics featuring in teaching resources are learner-centric and have been selected for their inherent relevance, interest and ability to excite and engage. Importantly, the resources coherently integrate and emphasise the overarching issues of sustainability, stewardship and critical thinking and the pervasive interdependencies of processes. More broadly, the concept emphasises how the multifarious applications of microbial activities can be leveraged to promote human/animal, plant, environmental and planetary health, improve social equity, alleviate humanitarian deficits and causes of conflicts among peoples and increase understanding between peoples (Microbial Biotechnology, 2023, 16(6), 1091-1111). Importantly, although the primary target of the freely available (CC BY-NC 4.0) IMiLI teaching resources is schoolchildren and their educators, they and the teaching philosophy are intended for all ages, abilities and cultural spectra of learners worldwide: in university education, lifelong learning, curiosity-driven, web-based knowledge acquisition and public outreach. The IMiLI teaching resources aim to promote development of a global microbiology education ecosystem that democratises microbiology knowledge.

Responsiveness of the condition-specific OVAMA questionnaire to measure symptoms and appearance in patients with vascular malformations.

BACKGROUND: Evidence-based guidelines for the treatment of vascular malformations are not readily available, possibly due to the diversity in methods used to evaluate treatment efficacy in clinical research, complicating the aggregation and comparison of study results. The OVAMA (Outcome Measures for VAscular Malformations) questionnaire was developed to uniformly measure symptoms and appearance, i.e., condition-specific core outcome domains, in patients with vascular malformations. However, the OVAMA questionnaire needs to be responsive to changes in these constructs in order to assess whether the disease status has altered since treatment. OBJECTIVES: To assess the responsiveness of the OVAMA questionnaire in patients with vascular malformations. METHODS: In a prospective longitudinal study, patients completed the OVAMA questionnaire at baseline and eight weeks follow-up since treatment or watchful waiting policy. Additionally, patients completed the Global rating of change (GRC) scales at follow-up. Responsiveness was evaluated following the criterion approach of testing predefined hypotheses about expected relationships between the OVAMA questionnaire and GRC scales, measuring the same constructs. The OVAMA questionnaire was considered responsive if ≥ 75% of the hypotheses were confirmed. RESULTS: Between July 2020 and September 2022, 89 patients were recruited in a vascular anomaly centre in the Netherlands, of which 63 patients completed the questionnaires at baseline and follow-up. In total, fifteen constructs of the OVAMA questionnaire were assessed for five hypotheses. Of these 75 hypotheses, 63 (84%) hypotheses were confirmed and thereby providing evidence that the OVAMA questionnaire is responsive to change. CONCLUSION: Our study found convincing evidence that the OVAMA questionnaire is responsive to changes in symptoms and appearance in patients with vascular malformations. In addition to determining a baseline of symptoms and appearance, the OVAMA questionnaire can now be used to evaluate the effect of treatment from the patient's perspective. The responsive OVAMA questionnaire allows for uniform evaluation and comparison of the effects of treatment on the condition-specific core outcome domains, tackling heterogeneity in outcome measurement and improving the clinical research of vascular malformations.

Proteomimetic Polymers Trigger Potent Antigen-Specific T Cell Responses to Limit Tumor Growth.

Elicitation of effective antitumor immunity following cancer vaccination requires the selective activation of distinct effector cell populations and pathways. Here we report a therapeutic approach for generating potent T cell responses using a modular vaccination platform technology capable of inducing directed immune activation, termed the Protein-like Polymer (PLP). PLPs demonstrate increased proteolytic resistance, high uptake by antigen-presenting cells (APCs), and enhanced payload-specific T cell responses. Key design parameters, namely payload linkage chemistry, degree of polymerization, and side chain composition, were varied to optimize vaccine formulations. Linking antigens to the polymer backbone using an intracellularly cleaved disulfide bond copolymerized with a diluent amount of oligo(ethylene glycol) (OEG) resulted in the highest payload-specific potentiation of antigen immunogenicity, enhancing dendritic cell (DC) activation and antigen-specific T cell responses. Vaccination with PLPs carrying either gp100, E7, or adpgk peptides significantly increased the survival of mice inoculated with B16F10, TC-1, or MC38 tumors, respectively, without the need for adjuvants. B16F10-bearing mice immunized with gp100-carrying PLPs showed increased antitumor CD8+ T cell immunity, suppressed tumor growth, and treatment synergy when paired with two distinct stimulator of interferon gene (STING) agonists. In a human papillomavirus-associated TC-1 model, combination therapy with PLP and 2'3'-cGAMP resulted in 40% of mice completely eliminating implanted tumors while also displaying curative protection from rechallenge, consistent with conferment of lasting immunological memory. Finally, PLPs can be stored long-term in a lyophilized state and are highly tunable, underscoring the unique properties of the platform for use as generalizable cancer vaccines.

Hepatocytes coordinate immune evasion in cancer via release of serum amyloid A proteins.

T cell infiltration into tumors is a favorable prognostic feature, but most solid tumors lack productive T cell responses. Mechanisms that coordinate T cell exclusion are incompletely understood. Here we identify hepatocyte activation via interleukin-6/STAT3 and secretion of serum amyloid A (SAA) proteins 1 and 2 as important regulators of T cell surveillance of extrahepatic tumors. Loss of STAT3 in hepatocytes or SAA remodeled the tumor microenvironment with infiltration by CD8+ T cells, while interleukin-6 overexpression in hepatocytes and SAA signaling via Toll-like receptor 2 reduced the number of intratumoral dendritic cells and, in doing so, inhibited T cell tumor infiltration. Genetic ablation of SAA enhanced survival after tumor resection in a T cell-dependent manner. Likewise, in individuals with pancreatic ductal adenocarcinoma, long-term survivors after surgery demonstrated lower serum SAA levels than short-term survivors. Taken together, these data define a fundamental link between liver and tumor immunobiology wherein hepatocytes govern productive T cell surveillance in cancer.

Treatment at relapse for synovial sarcoma of children and adolescents: A multi-institutional European retrospective analysis.

PURPOSE: Though the prognosis for pediatric patients with localised synovial sarcoma (SS) is generally good, the chances of being cured after relapse are limited. This study describes a retrospective multi-institutional series of relapsing SS patients treated at six selected European referral centers for pediatric sarcoma. PATIENTS AND METHODS: The study included 41 patients <21 years with relapsing SS, treated between 2002 and 2022. The analysis included patient's characteristics at first diagnosis, first-line treatments, clinical findings at relapse, and second-line treatment modalities. RESULTS: The first relapse occurred within 3-132 months (median 18 months) after first diagnosis and was local in 34%, metastatic in 54%, and both in 12%. Treatment at first relapse included surgery in 56% of cases, radiotherapy in 34%, and systemic therapy in 88%. In all, 36 patients received second-line medical treatment, that was chemotherapy in 32 cases (with 10 different regimens) and targeted therapy in four. No patient was included in an early-phase clinical trial as second-line therapy-line therapy. Overall response rate was 42%. Median event-free survival (EFS) was 12 months, postrelapse 5-year EFS was 15.8%. Median overall survival (OS) was 30 months, postrelapse 5-year OS was 22.2%. At the Cox's multivariable regression analysis, OS was significantly associated with time and type of relapse. CONCLUSION: Pediatric patients with relapsed SS have a poor prognosis and generally receive an individualized approach, due to the lack of a uniform standardized approach. New comprehensive strategies are needed to improve the knowledge on the biologic landscape of SS and develop tailored prospective clinical trials.

Effect of the DASH diet on the sodium-chloride cotransporter and aquaporin-2 in urinary extracellular vesicles.

The dietary approach to stop hypertension (DASH) diet combines the antihypertensive effect of a low sodium and high potassium diet. In particular, the potassium component of the diet acts as a switch in the distal convoluted tubule to reduce sodium reabsorption, similar to a diuretic but without the side effects. Previous trials to understand the mechanism of the DASH diet were based on animal models and did not characterize changes in human ion channel protein abundance. More recently, protein cargo of urinary extracellular vesicles (uEVs) has been shown to mirror tissue content and physiological changes within the kidney. We designed an inpatient open label nutritional study transitioning hypertensive volunteers from an American style diet to DASH diet to examine physiological changes in adults with stage 1 hypertension otherwise untreated (Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, Obarzanek E, Conlin PR, Miller ER 3rd, Simons-Morton DG, Karanja N, Lin PH; DASH-Sodium Collaborative Research Group. N Engl J Med 344: 3-10, 2001). Urine samples from this study were used for proteomic characterization of a large range of pure uEVs (small to large) to reveal kidney epithelium changes in response to the DASH diet. These samples were collected from nine volunteers at three time points, and mass spectrometry identified 1,800 proteins from all 27 samples. We demonstrated an increase in total SLC12A3 [sodium-chloride cotransporter (NCC)] abundance and a decrease in aquaporin-2 (AQP2) in uEVs with this mass spectrometry analysis, immunoblotting revealed a significant increase in the proportion of activated (phosphorylated) NCC to total NCC and a decrease in AQP2 from day 5 to day 11. This data demonstrates that the human kidney's response to nutritional interventions may be captured noninvasively by uEV protein abundance changes. Future studies need to confirm these findings in a larger cohort and focus on which factor drove the changes in NCC and AQP2, to which degree NCC and AQP2 contributed to the antihypertensive effect and address if some uEVs function also as a waste pathway for functionally inactive proteins rather than mirroring protein changes.NEW & NOTEWORTHY Numerous studies link DASH diet to lower blood pressure, but its mechanism is unclear. Urinary extracellular vesicles (uEVs) offer noninvasive insights, potentially replacing tissue sampling. Transitioning to DASH diet alters kidney transporters in our stage 1 hypertension cohort: AQP2 decreases, NCC increases in uEVs. This aligns with increased urine volume, reduced sodium reabsorption, and blood pressure decline. Our data highlight uEV protein changes as diet markers, suggesting some uEVs may function as waste pathways. We analyzed larger EVs alongside small EVs, and NCC in immunoblots across its molecular weight range.

Mo than meets the eye: genomic insights into molybdoenzyme diversity of Seleniivibrio woodruffii strain S4T.

Seleniivibrio woodruffii strain S4T is an obligate anaerobe belonging to the phylum Deferribacterota. It was isolated for its ability to respire selenate and was also found to respire arsenate. The high-quality draft genome of this bacterium is 2.9 Mbp, has a G+C content of 48%, 2762 predicted genes of which 2709 are protein-coding, and 53 RNA genes. An analysis of the genome focusing on the genes encoding for molybdenum-containing enzymes (molybdoenzymes) uncovered a remarkable number of genes encoding for members of the dimethylsulfoxide reductase family of proteins (DMSOR), including putative reductases for selenate and arsenate respiration, as well as genes for nitrogen fixation. Respiratory molybdoenzymes catalyze redox reactions that transfer electrons to a variety of substrates that can act as terminal electron acceptors for energy generation. Seleniivibrio woodruffii strain S4T also has essential genes for molybdate transporters and the biosynthesis of the molybdopterin guanine dinucleotide cofactors characteristic of the active centers of DMSORs. Phylogenetic analysis revealed candidate respiratory DMSORs spanning nine subfamilies encoded within the genome. Our analysis revealed the untapped potential of this interesting microorganism and expanded our knowledge of molybdoenzyme co-occurrence.

Relationship Between National Residency Matching Program (NRMP) Rank Order and Otolaryngology Residency Performance.

Objective: The process of resident recruitment is costly, and our surgical residency program expends significant time on the resident selection process while balancing general duties and responsibilities. The aim of our study was to explore the relationship between otolaryngology-head and surgery (OHNS) residents' National Residency Matching Program (NRMP) rank-list position at our institution and their subsequent residency performance. Study Design: Retrospective cohort study. Setting: Single site institution. Methods: We retrospectively reviewed 7 consecutive resident classes (2011-2017) at a single tertiary OHNS residency program. We reviewed each resident's absolute rank order in the NRMP matches. Measures of residency performance included overall faculty evaluation during postgraduate year 5 (PGY5), annual in-service examination scores (scaled score), and the number of manuscripts published in peer-reviewed journals. Correlations between NRMP rank order and subsequent residency performance were assessed using Spearman's rho correlation coefficients (ρ). Results: Twenty-eight residents entered residency training between 2011 and 2017. The average rank position of the trainees during this study was 9.7 (range: 1-22). We found no significant correlation between rank order and faculty evaluation during PGY5 (ρ = 0.097, P = .625) or number of publications (ρ = -0.256, P = .189). Additionally, when assessing the association between rank order and annual Otolaryngology Training Examination-scaled scores, no statistically significant relationship was found between the 2 (P > .05). Conclusion: Our results showed that there were no significant correlations between OHNS rank order and various measures of success in residency training, which aligns with existing literature. Further investigation of this relationship should be conducted to ensure the applicability of our findings.

Non-femoral focused transaxillary access in TAVI: GARY data analysis and future trends.

BACKGROUND: In patients not suitable for transfemoral transcatheter aortic valve implantation (TAVI), several access strategies can be chosen. AIM: To evaluate the use and patient outcomes of transaxillary (TAx), transapical (TA), and transaortic (TAo) as alternative access for TAVI in Germany; to further evaluate surgical cutdown vs. percutaneous TAx access. METHODS: All patients entered the German Aortic Valve Registry (GARY) between 2011 and 2019 who underwent non-transfemoral TAVI were included in this analysis. Patients with TA, TAo, or TAx TAVI were compared using a weighted propensity score model. Furthermore, a subgroup analysis was performed for TAx regarding the percutaneous or surgical cutdown approach. RESULTS: Overall, 9686 patients received a non-transfemoral access. A total of 8918 patients (92.1%) underwent TA, 398 (4.1%) TAo, and 370 (3.8%) TAx approaches. Within the TAx subgroup, 141 patients (38.1%) received subclavian cutdown, while 200 (54.1%) underwent a percutaneous approach. The TA patients had a significantly lower 30-day survival than TAx patients (TA 90.92% vs. TAx 95.59%, p = 0.006; TAo 92.22% vs. TAx 95.59%, p = 0.102). Comparing percutaneous and cutdown TAx approaches, no significant differences were seen. However, more vascular complications occurred (TA 1.8%, TAo 2.4%, TAx 12.2%; p < .001), and the hospital length of stay was shorter (TA 12.9 days, TAo 14.1 days, TAx 12 days; p < .001) after TAx access. CONCLUSION: It may be reasonable to consider TAx access first in patients not suitable for TF-TAVI, because the 30-day survival was higher compared with TA access and the 1-year survival was higher compared with TAo access. It remains important for the heart teams to offer alternative access modalities for patients not amenable to the standard TF-TAVI approaches.

Testing whether the relations between sex and psychopathology are accounted for by structural morphometry in ABCD.

Sex differences in psychopathology are well-established, with females demonstrating higher rates of internalizing (INT) psychopathology and males demonstrating higher rates of externalizing (EXT) psychopathology. Using two waves of data from the Adolescent Brain Cognitive Development Study (N = 6,778 at each wave), the current study tested whether the relations between sex and psychopathology might be accounted for by structural brain differences. In general, we found robust, relatively consistent relations between sex and structural morphometry across waves. Relatively few morphometric brain variables were significantly related to INT or EXT across waves, however, with very small effect sizes when present. Next, we tested the extent to which each morphometric brain variable could account for the associations of sex with INT and EXT psychopathology. We found a total of 26 brain regions that accounted for significant portions of the associations between sex and psychopathology across both waves (almost all related to EXT), although the effects present were very small. The current evidence suggests that in children aged 9-12, multiple whole-brain and regional brain variables appear to statistically account for small portions of the sex-psychopathology links, especially for externalizing. (PsycInfo Database Record (c) 2024 APA, all rights reserved).