Scientists' call to action: Microbes, planetary health, and the Sustainable Development Goals.

Microorganisms, including bacteria, archaea, viruses, fungi, and protists, are essential to life on Earth and the functioning of the biosphere. Here, we discuss the key roles of microorganisms in achieving the United Nations Sustainable Development Goals (SDGs), highlighting recent and emerging advances in microbial research and technology that can facilitate our transition toward a sustainable future. Given the central role of microorganisms in the biochemical processing of elements, synthesizing new materials, supporting human health, and facilitating life in managed and natural landscapes, microbial research and technologies are directly or indirectly relevant for achieving each of the SDGs. More importantly, the ubiquitous and global role of microbes means that they present new opportunities for synergistically accelerating progress toward multiple sustainability goals. By effectively managing microbial health, we can achieve solutions that address multiple sustainability targets ranging from climate and human health to food and energy production. Emerging international policy frameworks should reflect the vital importance of microorganisms in achieving a sustainable future.

Clinical perioperative outcomes in 39 cats after single session bilateral femoral head and neck excision.

OBJECTIVES: The aim of the study was to evaluate the perioperative outcomes and complications of single session bilateral femoral head and neck excision (FHNE) in cats for treatment of bilateral coxofemoral joint disease. METHODS: The medical records of cats undergoing a single session bilateral FHNE were identified and the history, signalment, diagnosis, surgery reports, anesthetic records, postoperative radiographs, postoperative examinations, complications and outcomes were recorded. RESULTS: A total of 39 cats undergoing a single session bilateral FHNE were included. Bilateral slipped capital femoral epiphysis was the most commonly diagnosed etiology. All cats were discharged within 48 h of the procedure. One major complication and five minor complications were reported. All but one cat returned to normal activity and no owners reported concerns after the 2-week postoperative recheck. CONCLUSIONS AND RELEVANCE: Single session bilateral FHNE is a viable surgical option for the treatment of bilateral coxofemoral disease in cats that results in a quick return to function, especially when other options are not indicated, available or affordable.

Total loss of VHL gene function impairs neuroendocrine cancer cell fitness due to excessive HIF2α activity.

Loss-of-function germline von Hippel-Lindau (VHL) tumor suppressor mutations cause VHL disease, which predisposes individuals to kidney cancer, hemangioblastomas, and paragangliomas. The risk that a given VHL disease family will manifest some or all these tumor types is profoundly influenced by the VHL allele it carries. For example, almost all VHL disease families that develop paraganglioma have missense VHL mutations. VHL families with null VHL alleles develop kidney cancer and hemangioblastomas without a high risk of paraganglioma. The latter is surprising because the VHL gene product, pVHL, suppresses the HIF2 transcription factor and gain-of-function HIF2 mutations are also linked to paraganglioma. Paragangliomas arise from the sympathetic or parasympathetic nervous system. Given the lack of human paraganglioma cell lines, we studied the effects of inactivating VHL in neuroblastoma cell lines, which also arise from the sympathetic nervous system. We found that total loss of pVHL function profoundly impairs the fitness of neuroblastoma cell lines in a HIF2-dependent manner both ex vivo and in vivo. This fitness defect can be rescued by pVHL variants linked to paraganglioma, but not by pVHL variants associated with a low risk of paraganglioma. These findings suggest that HIF2 activity above a critical threshold prevents the development of paraganglioma.

Blocking tryptophan catabolism reduces triple-negative breast cancer invasive capacity.

Anchorage-independent triple-negative breast cancer (TNBC) cells exhibit elevated levels of the tryptophan (TRP) catabolizing enzyme tryptophan 2,3-dioxygenase 2 (TDO2) compared to the same cells grown in two-dimensional culture. Tracing of 13C11-TRP demonstrated that anchorage-independent culture and/or inflammatory cytokines that activate nuclear factor kappa-light-chain-enhancer of activated B (NFκB) increase TRP catabolism and production of downstream catabolites such as kynurenine (KYN), which activate the aryl hydrocarbon receptor (AhR). TDO2 expression is heterogeneous within TNBC cell lines. To determine the function of TDO2, both pharmacologic inhibition and genetic manipulation were conducted. TDO2 knockdown revealed a compensatory increase in indoleamine 2,3-dioxygenase 1 (IDO1), a non-homologous TRP catabolizing enzyme, indicating that dual inhibition of these two enzymes is necessary to reliably block TRP catabolism. Thus, we tested a newly developed TDO2/IDO1 dual inhibitor, AT-0174, and found that it effectively inhibits TNBC TRP catabolism. Furthermore, AT-0174 treatment or AhR inhibitor significantly decreased TNBC anchorage-independent survival, invasive capacity, and expression of mesenchymal genes and protein, while exogenous KYN increased invasion through AhR-mediated ZEB1 expression. Thus, dual inhibition of TDO2/IDO1 may prove efficacious against TNBC progression.

Decoupling of strain- and intrastrain-level interactions of microbiomes in a sponge holobiont.

Holobionts are highly organized assemblages of eukaryotic hosts, cellular microbial symbionts, and viruses, whose interactions and evolution involve complex biological processes. It is largely unknown which specific determinants drive similarity or individuality in genetic diversity between holobionts. Here, we combine short- and long-read sequencing and DNA-proximity-linkage technologies to investigate intraspecific diversity of the microbiomes, including host-resolved viruses, in individuals of a model marine sponge. We find strong impacts of the sponge host and the cellular hosts of viruses on strain-level organization of the holobiont, whereas substantial overlap in nucleotide diversity between holobionts suggests frequent exchanges of microbial cells and viruses at intrastrain level in the local sponge population. Immune-evasive arms races likely restricted virus-host co-evolution at the intrastrain level, generated holobiont-specific genome variations, and linked virus-host genetics through recombination. Our work shows that a decoupling of strain- and intrastrain-level interactions is a key factor in the genetic diversification of holobionts.

Covalently crosslinked coacervates: immobilization and stabilization of proteins with enhanced enzymatic activity.

Coacervates represent models for membrane-free protocells and thus provide a simple route to synthetic cellular-like systems that provide selective encapsulation of solutes. Here, we demonstrate a simple and versatile post-coacervation crosslink method using the thiol-ene click reaction in aqueous media to prepare covalently crosslinked coacervates. The crosslinking of the coacervate enables stability at extreme pH where the uncrosslinked coacervate fully disassembles. The crosslinking also enhances the hydrophobicity within the coacervate environment to increase the encapsulation efficiency of bovine serum albumin (BSA), as compared to the uncrosslinked coacervate. Additionally, the crosslinked coacervate increases the stabilization of BSA at low pH. These crosslinked coacervates can act as carriers for enzymes. The enzymatic activity of alkaline phosphatase (ALP) is enhanced within the crosslinked coacervate compared to the ALP in aqueous solution. The post-coacervation crosslink approach allows the utilization of coacervates for encapsulation of biologicals under conditions where the coacervate would generally disassemble. We demonstrate that these crosslinked coacervates enable the protection of encapsulated protein against denaturation at extreme pH and enhance the enzymatic activity with encapsulation. This click approach to stabilization of coacervates should be broadly applicable to other systems for a variety of biologics and environmentally sensitive molecules.

A mechanistic framework for complex microbe-host symbioses.

Virtually all multicellular organisms on Earth live in symbiotic associations with complex microbial communities: the microbiome. This ancient relationship is of fundamental importance for both the host and the microbiome. Recently, the analyses of numerous microbiomes have revealed an incredible diversity and complexity of symbionts, with different mechanisms identified as potential drivers of this diversity. However, the interplay of ecological and evolutionary forces generating these complex associations is still poorly understood. Here we explore and summarise the suite of ecological and evolutionary mechanisms identified as relevant to different aspects of microbiome complexity and diversity. We argue that microbiome assembly is a dynamic product of ecology and evolution at various spatio-temporal scales. We propose a theoretical framework to classify mechanisms and build mechanistic host-microbiome models to link them to empirical patterns. We develop a cohesive foundation for the theoretical understanding of the combined effects of ecology and evolution on the assembly of complex symbioses.

Comparative genomics identifies key adaptive traits of sponge-associated microbial symbionts.

Sponge microbiomes are often highly diverse making it difficult to determine which lineages are important for maintaining host health and homeostasis. Characterising genomic traits associated with symbiosis can improve our knowledge of which lineages have adapted to their host and what functions they might provide. Here we examined five microbial families associated with sponges that have previously shown evidence of cophylogeny, including Endozoicomonadaceae, Nitrosopumilaceae, Spirochaetaceae, Microtrichaceae and Thermoanaerobaculaceae, to better understand the mechanisms behind their symbiosis. We compared sponge-associated genomes to genomes found in other environments and found that sponge-specific clades were enriched in genes encoding many known mechanisms for symbiont survival, such as avoiding phagocytosis and defence against foreign genetic elements. We expand on previous knowledge to show that glycosyl hydrolases with sulfatases and sulfotransferases likely form multienzyme degradation pathways to break and remodel sulfated polysaccharides and reveal an enrichment in superoxide dismutase that may prevent damage from free oxygen radicals produced by the host. Finally, we identified novel traits in sponge-associated symbionts, such as urea metabolism in Spirochaetaceae which was previously shown to be rare in the phylum Spirochaetota. These results identify putative mechanisms by which symbionts have adapted to living in association with sponges.

Prevalence, Best Practice Use, and Member Engagement on School Mental Health Teams.

School mental health (SMH) teams have been widely recommended to support multi-tiered mental health program implementation in schools. Available research suggests emerging best practices that promote effective SMH teaming and indicates the importance of having team members who are highly engaged (e.g., actively involved, retained on the team). Despite evidence that these factors improve team functioning, there is limited knowledge of SMH team prevalence, best practice use, and factors impacting member engagement among a diverse sample of elementary schools. This study surveyed a cross-sectional sample of elementary principals (n = 314) across the United States whose schools implement multi-tiered SMH programs. Most principals (89%, n = 280) reported using teams to organize these programs. Schools in urban/suburban communities, with 300 or more students, or with specific school funding for SMH activities were more likely to have SMH teams. Only one-third of principals reported that their team members participated in related training. Other SMH team best practices were commonly reported (by two-thirds or more teams). Results of a linear regression model indicate that larger teams (six or more members) and teams with access to resources had significantly higher member engagement scores. The study's findings provide recommendations for practice and future research directions.

Giant molluscum contagiosum with preseptal cellulitis.

Molluscum contagiosum (MC) is a benign cutaneous viral infection commonly affecting children, sexually active adults, immunocompromised individuals, and patients on immunosuppressive therapy. Giant periorbital MC lesions with preseptal cellulitis are rare. We present 2 such pediatric cases. Case 1 was a 9-month-old boy with an enlarging left upper eyelid mass and preseptal cellulitis. MC was confirmed on histopathology, and surgical excision was curative. Case 2 was an 18-month-old girl with a right lower eyelid ulcerating mass and preseptal cellulitis. She was managed with antibiotics and surgical excision.

Anatomical classification of canine congenital extrahepatic portosystemic shunts based on CT angiography: A SVSTS and VIRIES multi-institutional study in 1082 dogs.

Canine congenital extrahepatic portosystemic shunt (EHPSS) morphologies have not been fully elucidated. The goal of this retrospective, multi-institutional study was to use CT angiography to create an anatomical-based nomenclature system for canine congenital EHPSS. These shunt morphologies were then evaluated to identify any significant association with patient age, sex, breed, weight, or subjective portal perfusion score. Data collected respectively from the SVSTS and VIRIES list-serves included patient DOB, sex, breed, weight, CT date, and reported diagnosis. A single author (C.W.) viewed all CT scans and classified shunts based on the shunt portal vessel(s) of origin, the shunt systemic vessel(s) of insertion, and any substantial portal vessels contributing to the shunt. Additionally, hepatic portal perfusion was subjectively scored between one (poor/none) and five (good/normal) based on the caliber of the intrahepatic portal veins. A total of 1182 CT scans were submitted from 13 different institutions. Due to exclusion criteria, 100 (8.5%) were removed, leaving 1082 CT scans to be included. Forty-five different EHPSS anatomies were identified with five classifications accounting for 85% of all shunts (left gastric-phrenic [27%], left gastric-azygos [19%], left gastric-caval [15%], aberrant left gastric-caval with right gastric vein [12%], and aberrant left gastric-caval with right gastric vein and short gastric vein [11%]). Shunt origin involved the left gastric vein in 95% of the described classifications. Significant differences were identified among the five most common shunt types with respect to age at the time of the CT scan (P < .001), sex (P = .009), breed (P < .001), weight (P < .001), and subjective portal perfusion score (P < .001). An anatomical classification system for canine EHPSS may enable improved understanding, treatment comparisons, and outcome prediction for these patients.

Solving a diagnostic dilemma in a patient with periodic fever-When the pieces of the puzzle finally fit.

The lack of pediatric subspecialists locally prior to 5 years ago, meant that some of our patients with rare, relapsing conditions were left behind. Familial Mediterranean fever can be diagnosed clinically and supported via genetic panel studies. Although neurological symptoms can be non-specific, this system symptomatology may lead patients and carers to seek medical attention. When neurological symptoms progress, seemingly refractory to first-line treatment, or suggestive of colchicine resistance, CNS demyelination should be considered by the neurologist. Abstract: Familial Mediterranean fever (FMF) is an inherited disorder with episodic fevers accompanied by pain in the abdomen, joints, or chest. It is a clinical entity that can be confirmed with a specific genetic mutation. Neurological symptoms have not been a focal point in clinical case descriptions. We aim to present the long road to diagnosing our patient, where the diagnostic clues centered around her neurological symptoms.

Stressors and subjective cognition in daily life: Tests of physical activity and age as moderators.

OBJECTIVE: Growing research indicates that daily stress is associated with poorer same-day cognitive performance, for example, memory and attention. However, it is unclear whether this relationship holds across diverse ages and engagement in physical activity (PA), or whether these factors might buffer the relationship between daily stress and subjective cognitive function. METHODS: Ecological momentary assessment data were collected from adults aged 25-88 across British Columbia, Canada. For 14 days, participants (N = 204) wore a tri-axial physical activity monitor, reported stressor occurrence in mobile surveys 4 times per day, and rated their subjective attention and memory at the end of each day. RESULTS: Multilevel models evaluated daily stressor occurrence as a predictor of subjective attention and memory, with same-day PA engagement and age as moderators. Subjective attention and memory were lower on days when a stressor had occurred, compared to stressor-free days. Neither PA nor age moderated the within-person associations of daily stressors with subjective cognition. CONCLUSION: The lack of stress-buffering effects for same-day PA and age raises questions about the contexts in which PA promotes cognitive functioning and about age-related processes underlying stress and cognition. Future work could examine the mechanisms that might explain the link between daily stress and cognition function, as well as the associations of different intensity and forms of physical activity on stress across age groups.

Incidence and prevalence of primary biliary cholangitis in the Netherlands - A nationwide cohort study.

Background & Aims: Although primary biliary cholangitis (PBC) is considered a rare disorder, accurate determination of its incidence and prevalence remains challenging due to limited comprehensive population-based registries. We aimed to assess the incidence and prevalence of PBC in the Netherlands over time through the nationwide Dutch PBC Cohort Study (DPCS). Methods: DPCS retrospectively included every identifiable patient with PBC in the Netherlands from 1990 onwards in all 71 Dutch hospitals. Incidence and prevalence were assessed between 2008-2018 by Poisson regression between sex and age groups over time. Results: On the 1st of January 2008, there were 1,458 patients with PBC in the Netherlands. Between 2008-2018, 2,187 individuals were newly diagnosed, 46 were transplanted and 468 died. The yearly incidence of PBC in 2008 was 1.38, increasing to 1.74 per 100,000 persons in 2018. When compared to those aged <45 years, females aged 45-64 years (adjusted incidence rate ratio 4.21, 95% CI 3.76-4.71, p <0.001) and males ≥65 years (adjusted incidence rate ratio 14.41, 95% CI 9.62-21.60, p <0.001) were at the highest risk of being diagnosed with PBC. The male-to-female ratio of patients newly diagnosed with PBC during the study period was 1:14 in those <45 years, 1:10 in patients aged 45-64 years, and 1:4 in those ≥65 years. Point prevalence increased from 11.9 in 2008 to 21.5 per 100,000 persons in 2018. Average annual percent change in this time period was 5.94% (95% CI 5.77-6.15, p <0.05), and was the highest among the population aged ≥65 years (5.69%, 95% CI 5.32-6.36, p <0.001). Conclusions: In this nationwide cohort study, we observed an increase in both the incidence and prevalence of PBC in the Netherlands over the past decade, with marked age and sex differences. Impact and implications: This nationwide Dutch primary biliary cholangitis (PBC) Cohort Study, including all hospitals in the Netherlands, showed that the incidence and prevalence of PBC have increased over the last decade. The age-dependent PBC incidence rate differed for males (highest risk ≥65 years) and females (highest risk between 45 and 65 years), which may be related to a difference in the timing of exposure to environmental triggers of PBC. The largest increase in PBC prevalence over time was observed in the population aged ≥65 years, which may have implications for the use of second-line therapies. These results therefore indicate that further studies are needed to elaborate on the advantages and disadvantages of add-on therapies in the elderly population.

Trends and adverse pregnancy and birth outcomes associated with stimulant-related disorder diagnosis.

BACKGROUND AND AIMS: Stimulant-related disorders (SRD), or the continued misuse of illicit or prescribed stimulants, during pregnancy can have adverse health effects for mothers and infants. This study aimed to measure prevalence and trends of SRD diagnosis in pregnancy, and associations between SRD diagnosis and adverse maternal and infant health outcomes, among pregnant individuals in California. DESIGN: Retrospective cohort study. SETTING: California, USA. PARTICIPANTS: Pregnant individuals from the Study of Outcomes in Mothers and Infants (SOMI) with singleton live births between 2012 and 2020 (n = 3 740 079). MEASUREMENTS: SRD diagnosis (excluding cocaine) and maternal (gestational diabetes, gestational hypertension [gHTN], severe maternal morbidity [SMM]) and infant (very preterm birth [gestational age <32 weeks], preterm birth [gestational age 32-37 weeks], neonatal intensive care unit [NICU] admission, small for gestational age [SGA]) outcomes were classified using International Classification of Disease (ICD) codes and vital statistics. Risk ratios were estimated with modified Poisson log linear regression that accounted for sibling pregnancies. Covariates included maternal sociodemographic characteristics, mental and physical health problems, nicotine use and co-occurrence of other diagnosed substance use disorders. Bias analyses were conducted to address unmeasured confounding and exposure misclassification. FINDINGS: SRD diagnosis among pregnant individuals increased from 2012 to 2020 (554 to 748 per 100 000 births). SRD diagnosis was associated with an increased risk of SMM (adjusted risk ratio [aRR] = 2.3; 95% confidence interval [CI] = 2.2-2.5), gHTN (aRR = 1.8; 95% CI = 1.7-1.9), very preterm birth (aRR = 2.2, 95% CI = 2.0-2.5), preterm birth (aRR = 2.1, 95% CI = 2.1-2.2) and NICU admission (aRR = 2.0, 95%CI = 1.9-2.0), and a decreased risk of gestational diabetes (aRR = 0.8; 95% CI = 0.8-0.9). SRD diagnosis was not associated with infants born SGA. Findings were generally robust to unmeasured confounding and misclassification of diagnosis. CONCLUSIONS: Stimulant-related disorder diagnosis during pregnancy appears to be associated with an increased risk for select adverse maternal and infant health outcomes including severe maternal morbidity, gestational hypertension, very preterm birth, preterm birth and neonatal intensive care unit admission.

Detection of residual pluripotent stem cells in cell therapy products utilizing droplet digital PCR: an international multisite evaluation study.

The presence of residual undifferentiated pluripotent stem cells (PSCs) in PSC-derived cell therapy products (CTPs) is a major safety issue for their clinical application, due to the potential risk of PSC-derived tumor formation. An international multidisciplinary multisite study to evaluate a droplet digital PCR (ddPCR) approach to detect residual undifferentiated PSCs in PSC-derived CTPs was conducted as part of the Health and Environmental Sciences Institute Cell Therapy-TRAcking, Circulation & Safety Technical Committee. To evaluate the use of ddPCR in quantifying residual iPSCs in a cell sample, different quantities of induced pluripotent stem cells (iPSCs) were spiked into a background of iPSC-derived cardiomyocytes (CMs) to mimic different concentrations of residual iPSCs. A one step reverse transcription ddPCR (RT-ddPCR) was performed to measure mRNA levels of several iPSC-specific markers and to evaluate the assay performance (precision, sensitivity, and specificity) between and within laboratories. The RT-ddPCR assay variability was initially assessed by measuring the same RNA samples across all participating facilities. Subsequently, each facility independently conducted the entire process, incorporating the spiking step, to discern the parameters influencing potential variability. Our results show that a RT-ddPCR assay targeting ESRG, LINC00678, and LIN28A genes offers a highly sensitive and robust detection of impurities of iPSC-derived CMs and that the main contribution to variability between laboratories is the iPSC-spiking procedure, and not the RT-ddPCR. The RT-ddPCR assay would be generally applicable for tumorigenicity evaluation of PSC-derived CTPs with appropriate marker genes suitable for each CTP.

Biomechanical Assessment of Liver Integrity: Prospective Evaluation of Mechanical Versus Acoustic MR Elastography.

BACKGROUND: Magnetic resonance elastography (MRE) can quantify tissue biomechanics noninvasively, including pathological hepatic states like metabolic dysfunction-associated steatohepatitis. PURPOSE: To compare the performance of 2D/3D-MRE using the gravitational (GT) transducer concept with the current commercial acoustic (AC) solution utilizing a 2D-MRE approach. Additionally, quality index markers (QIs) were proposed to identify image pixels with sufficient quality for reliably estimating tissue biomechanics. STUDY TYPE: Prospective. POPULATION: One hundred seventy participants with suspected or confirmed liver disease (median age, 57 years [interquartile range (IQR), 46-65]; 66 females), and 11 healthy volunteers (median age, 31 years [IQR, 27-34]; 5 females). FIELD STRENGTH/SEQUENCE: Participants were scanned twice at 1.5 T and 60 Hz vibration frequency: first, using AC-MRE (2D-MRE, spin-echo EPI sequence, 11 seconds breath-hold), and second, using GT-MRE (2D- and 3D-MRE, gradient-echo sequence, 14 seconds breath-hold). ASSESSMENT: Image analysis was performed by four independent radiologists and one biomedical engineer. Additionally, superimposed analytic plane shear waves of known wavelength and attenuation at fixed shear modulus were used to propose pertinent QIs. STATISTICAL TESTS: Spearman's correlation coefficient (r) was applied to assess the correlation between modalities. Interreader reproducibility was evaluated using Bland-Altman bias and reproducibility coefficients. P-values <0.05 were considered statistically significant. RESULTS: Liver stiffness quantified via GT-2D/3D correlated well with AC-2D (r ≥ 0.89 [95% CI: 0.85-0.92]) and histopathological grading (r ≥ 0.84 [95% CI: 0.72-0.91]), demonstrating excellent agreement in Bland-Altman plots and between readers (κ ≥ 0.86 [95% CI: 0.81-0.91]). However, GT-2D showed a bias in overestimating stiffness compared to GT-3D. Proposed QIs enabled the identification of pixels deviating beyond 10% from true stiffness based on a combination of total wave amplitude, temporal sinusoidal nonlinearity, and wave signal-to-noise ratio for GT-3D. CONCLUSION: GT-MRE represents an alternative to AC-MRE for noninvasive liver tissue characterization. Both GT-2D and 3D approaches correlated strongly with the established commercial approach, offering advanced capabilities in abdominal imaging compared to AC-MRE. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Glycopolymers Prepared by Alternating Ring-Opening Metathesis Polymerization Provide Access to Distinct, Multivalent Structures for the Probing of Biological Activity.

A myriad of biological processes are facilitated by ligand-receptor interactions. The low affinities of these interactions are typically enhanced by multivalent engagements to promote binding. However, each biological interaction requires a unique display and orientation of ligands. Therefore, the availability and diversity of synthetic multivalent probes are invaluable to the investigation of ligand-receptor binding interactions. Here, we report glycopolymers prepared from bicyclo[4.2.0]oct-6-ene-7-carboxamide and 4,7-dihydro-1,3-dioxepin or cyclohexene. These glycopolymers, synthesized by alternating ring-opening metathesis polymerization, display precise ligand spacing as well as the option of a hydrophobic or acetal-functionalized polymer backbone. Small-angle X-ray scattering (SAXS) data analysis revealed that these [4.2.0] glycopolymers adopted distinct conformations in solution. In aqueous media, [4.2.0]-dioxepin glycopolymers formed swollen polymer chains with rod-like, flexible structures while [4.2.0]-cyclohexene glycopolymers assumed compact, globular structures. To illustrate how these glycopolymers could aid in the exploration of ligand-receptor interactions, we incorporated the [4.2.0] glycopolymers into a biological assay to assess their potential as activators of acrosomal exocytosis (AE) in mouse sperm. The results of the biological assay confirmed that the differing structures of the [4.2.0] glycopolymers would evoke distinct biological responses; [4.2.0]-cyclohexene glycopolymers induced AE in mouse sperm while [4.2.0]-dioxepin glycopolymers did not. Herein, we provide two options for glycopolymers with low to moderate molecular weight dispersities and low cytotoxicity that can be implemented into biological assays based on the desired hydrophobicity, rigidity, and structural conformation of the polymer probe.

Uncovering the hidden effects of repetitive subconcussive head impact exposure: A mega-analytic approach characterizing seasonal brain microstructural changes in contact and collision sports athletes.

Repetitive subconcussive head impacts (RSHI) are believed to induce sub-clinical brain injuries, potentially resulting in cumulative, long-term brain alterations. This study explores patterns of longitudinal brain white matter changes across sports with RSHI-exposure. A systematic literature search identified 22 datasets with longitudinal diffusion magnetic resonance imaging data. Four datasets were centrally pooled to perform uniform quality control and data preprocessing. A total of 131 non-concussed active athletes (American football, rugby, ice hockey; mean age: 20.06 ± 2.06 years) with baseline and post-season data were included. Nonparametric permutation inference (one-sample t tests, one-sided) was applied to analyze the difference maps of multiple diffusion parameters. The analyses revealed widespread lateralized patterns of sports-season-related increases and decreases in mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) across spatially distinct white matter regions. Increases were shown across one MD-cluster (3195 voxels; mean change: 2.34%), one AD-cluster (5740 voxels; mean change: 1.75%), and three RD-clusters (817 total voxels; mean change: 3.11 to 4.70%). Decreases were shown across two MD-clusters (1637 total voxels; mean change: -1.43 to -1.48%), two RD-clusters (1240 total voxels; mean change: -1.92 to -1.93%), and one AD-cluster (724 voxels; mean change: -1.28%). The resulting pattern implies the presence of strain-induced injuries in central and brainstem regions, with comparatively milder physical exercise-induced effects across frontal and superior regions of the left hemisphere, which need further investigation. This article highlights key considerations that need to be addressed in future work to enhance our understanding of the nature of observed white matter changes, improve the comparability of findings across studies, and promote data pooling initiatives to allow more detailed investigations (e.g., exploring sex- and sport-specific effects).