Single-cell atlas reveals correlates of high cognitive function, dementia, and resilience to Alzheimer's disease pathology.

Alzheimer's disease (AD) is the most common cause of dementia worldwide, but the molecular and cellular mechanisms underlying cognitive impairment remain poorly understood. To address this, we generated a single-cell transcriptomic atlas of the aged human prefrontal cortex covering 2.3 million cells from postmortem human brain samples of 427 individuals with varying degrees of AD pathology and cognitive impairment. Our analyses identified AD-pathology-associated alterations shared between excitatory neuron subtypes, revealed a coordinated increase of the cohesin complex and DNA damage response factors in excitatory neurons and in oligodendrocytes, and uncovered genes and pathways associated with high cognitive function, dementia, and resilience to AD pathology. Furthermore, we identified selectively vulnerable somatostatin inhibitory neuron subtypes depleted in AD, discovered two distinct groups of inhibitory neurons that were more abundant in individuals with preserved high cognitive function late in life, and uncovered a link between inhibitory neurons and resilience to AD pathology.

Rapid detection of IDH mutations in gliomas by intraoperative mass spectrometry.

The development and performance of two mass spectrometry (MS) workflows for the intraoperative diagnosis of isocitrate dehydrogenase (IDH) mutations in glioma is implemented by independent teams at Mayo Clinic, Jacksonville, and Huashan Hospital, Shanghai. The infiltrative nature of gliomas makes rapid diagnosis necessary to guide the extent of surgical resection of central nervous system (CNS) tumors. The combination of tissue biopsy and MS analysis used here satisfies this requirement. The key feature of both described methods is the use of tandem MS to measure the oncometabolite 2-hydroxyglutarate (2HG) relative to endogenous glutamate (Glu) to characterize the presence of mutant tumor. The experiments i) provide IDH mutation status for individual patients and ii) demonstrate a strong correlation of 2HG signals with tumor infiltration. The measured ratio of 2HG to Glu correlates with IDH-mutant (IDH-mut) glioma (P < 0.0001) in the tumor core data of both teams. Despite using different ionization methods and different mass spectrometers, comparable performance in determining IDH mutations from core tumor biopsies was achieved with sensitivities, specificities, and accuracies all at 100%. None of the 31 patients at Mayo Clinic or the 74 patients at Huashan Hospital were misclassified when analyzing tumor core biopsies. Robustness of the methodology was evaluated by postoperative re-examination of samples. Both teams noted the presence of high concentrations of 2HG at surgical margins, supporting future use of intraoperative MS to monitor for clean surgical margins. The power of MS diagnostics is shown in resolving contradictory clinical features, e.g., in distinguishing gliosis from IDH-mut glioma.

SARS-CoV-2 Seropositivity in Urban Population of Wild Fallow Deer, Dublin, Ireland, 2020-2022.

SARS-CoV-2 can infect wildlife, and SARS-CoV-2 variants of concern might expand into novel animal reservoirs, potentially by reverse zoonosis. White-tailed deer and mule deer of North America are the only deer species in which SARS-CoV-2 has been documented, raising the question of whether other reservoir species exist. We report cases of SARS-CoV-2 seropositivity in a fallow deer population located in Dublin, Ireland. Sampled deer were seronegative in 2020 when the Alpha variant was circulating in humans, 1 deer was seropositive for the Delta variant in 2021, and 12/21 (57%) sampled deer were seropositive for the Omicron variant in 2022, suggesting host tropism expansion as new variants emerged in humans. Omicron BA.1 was capable of infecting fallow deer lung type-2 pneumocytes and type-1-like pneumocytes or endothelial cells ex vivo. Ongoing surveillance to identify novel SARS-CoV-2 reservoirs is needed to prevent public health risks during human-animal interactions in periurban settings.

Advancing One human-animal-environment Health for global health security: what does the evidence say?

In this Series paper, we review the contributions of One Health approaches (ie, at the human-animal-environment interface) to improve global health security across a range of health hazards and we summarise contemporary evidence of incremental benefits of a One Health approach. We assessed how One Health approaches were reported to the Food and Agricultural Organization of the UN, the World Organisation for Animal Health (WOAH, formerly OIE), and WHO, within the monitoring and assessment frameworks, including WHO International Health Regulations (2005) and WOAH Performance of Veterinary Services. We reviewed One Health theoretical foundations, methods, and case studies. Examples from joint health services and infrastructure, surveillance-response systems, surveillance of antimicrobial resistance, food safety and security, environmental hazards, water and sanitation, and zoonoses control clearly show incremental benefits of One Health approaches. One Health approaches appear to be most effective and sustainable in the prevention, preparedness, and early detection and investigation of evolving risks and hazards; the evidence base for their application is strongest in the control of endemic and neglected tropical diseases. For benefits to be maximised and extended, improved One Health operationalisation is needed by strengthening multisectoral coordination mechanisms at national, regional, and global levels.

A vector system for single and tandem expression of cloned genes and multi-colour fluorescent tagging in Haloferax volcanii.

Archaeal cell biology is an emerging field expected to identify fundamental cellular processes, help resolve the deep evolutionary history of cellular life, and contribute new components and functions in biotechnology and synthetic biology. To facilitate these, we have developed plasmid vectors that allow convenient cloning and production of proteins and fusion proteins with flexible, rigid, or semi-rigid linkers in the model archaeon Haloferax volcanii. For protein subcellular localization studies using fluorescent protein (FP) tags, we created vectors incorporating a range of codon-optimized fluorescent proteins for N- or C-terminal tagging, including GFP, mNeonGreen, mCherry, YPet, mTurquoise2 and mScarlet-I. Obtaining functional fusion proteins can be challenging with proteins involved in multiple interactions, mainly due to steric interference. We demonstrated the use of the new vector system to screen for improved function in cytoskeletal protein FP fusions, and identified FtsZ1-FPs that are functional in cell division and CetZ1-FPs that are functional in motility and rod cell development. Both the type of linker and the type of FP influenced the functionality of the resulting fusions. The vector design also facilitates convenient cloning and tandem expression of two genes or fusion genes, controlled by a modified tryptophan-inducible promoter, and we demonstrated its use for dual-colour imaging of tagged proteins in H. volcanii cells. These tools should promote further development and applications of archaeal molecular and cellular biology and biotechnology.

JYNNEOS Vaccine Safety Surveillance During the 2022 Mpox Outbreak Using the Vaccine Adverse Event Reporting System and V-safe, United States, 2022 to 2023.

BACKGROUND: In response to the 2022 mpox outbreak in the United States, people with higher potential for exposure to mpox were recommended to receive 2 doses of the JYNNEOS vaccine. Vaccine safety was monitored using 2 complementary systems. METHODS: The Vaccine Adverse Event Reporting System (VAERS) is a passive surveillance system that accepts reports of adverse events after vaccination. VAERS is capable of rapidly identifying rare adverse events and unusual reporting patterns. Medical records were requested and reviewed for adverse events of special interest, including myocarditis. Adverse event reporting rates were calculated as the number of verified adverse event cases divided by the number of JYNNEOS doses administered. V-safe for mpox was a voluntary smartphone-based vaccine safety surveillance system that sent enrolled persons text messages linked to health surveys asking about reactions and health impact events occurring after vaccination. RESULTS: There were 1,207,056 JYNNEOS doses administered in the United States. VAERS received 1927 reports for JYNNEOS. The myocarditis reporting rate per million doses was 2.69 after dose 1 and 8.64 after dose 2. V-safe had 213 participants complete at least one health survey. Rates of injection site and systemic reactions were similar in the first week after dose 1 and dose 2. CONCLUSIONS: JYNNEOS vaccine safety surveillance findings from VAERS and v-safe did not identify any unexpected safety concerns. The VAERS reporting rate for myocarditis was similar to previously published population background rates.

Perception of structurally distinct effectors by the integrated WRKY domain of a plant immune receptor.

Plants use intracellular nucleotide-binding domain (NBD) and leucine-rich repeat (LRR)-containing immune receptors (NLRs) to detect pathogen-derived effector proteins. The Arabidopsis NLR pair RRS1-R/RPS4 confers disease resistance to different bacterial pathogens by perceiving the structurally distinct effectors AvrRps4 from Pseudomonas syringae pv. pisi and PopP2 from Ralstonia solanacearum via an integrated WRKY domain in RRS1-R. How the WRKY domain of RRS1 (RRS1WRKY) perceives distinct classes of effector to initiate an immune response is unknown. Here, we report the crystal structure of the in planta processed C-terminal domain of AvrRps4 (AvrRps4C) in complex with RRS1WRKY Perception of AvrRps4C by RRS1WRKY is mediated by the ß2-ß3 segment of RRS1WRKY that binds an electronegative patch on the surface of AvrRps4C Structure-based mutations that disrupt AvrRps4C-RRS1WRKY interactions in vitro compromise RRS1/RPS4-dependent immune responses. We also show that AvrRps4C can associate with the WRKY domain of the related but distinct RRS1B/RPS4B NLR pair, and the DNA-binding domain of AtWRKY41, with similar binding affinities and how effector binding interferes with WRKY-W-box DNA interactions. This work demonstrates how integrated domains in plant NLRs can directly bind structurally distinct effectors to initiate immunity.

Optical imaging detects metabolic signatures associated with oocyte quality†.

Oocyte developmental potential is intimately linked to metabolism. Existing approaches to measure metabolism in the cumulus oocyte complex (COC) do not provide information on the separate cumulus and oocyte compartments. Development of an assay that achieves this may lead to an accurate diagnostic for oocyte quality. Optical imaging of the autofluorescent cofactors reduced nicotinamide adenine dinucleotide (phosphate) [NAD(P)H] and flavin adenine dinucleotide (FAD) provides a spatially resolved indicator of metabolism via the optical redox ratio (FAD/[NAD(P)H + FAD]). This may provide an assessment of oocyte quality. Here, we determined whether the optical redox ratio is a robust methodology for measuring metabolism in the cumulus and oocyte compartments compared with oxygen consumption in the whole COC. We also determined whether optical imaging could detect metabolic differences associated with poor oocyte quality (etomoxir-treated). We used confocal microscopy to measure NAD(P)H and FAD, and extracellular flux to measure oxygen consumption. The optical redox ratio accurately reflected metabolism in the oocyte compartment when compared with oxygen consumption (whole COC). Etomoxir-treated COCs showed significantly lower levels of NAD(P)H and FAD compared to control. We further validated this approach using hyperspectral imaging, which is clinically compatible due to its low energy dose. This confirmed lower NAD(P)H and FAD in etomoxir-treated COCs. When comparing hyperspectral imaged vs non-imaged COCs, subsequent preimplantation development and post-transfer viability were comparable. Collectively, these results demonstrate that label-free optical imaging of metabolic cofactors is a safe and sensitive assay for measuring metabolism and has potential to assess oocyte developmental competence.

Chloroplasts play a central role in facilitating MAMP-triggered immunity, pathogen suppression of immunity and crosstalk with abiotic stress.

Microbe-associated molecular pattern (MAMP)-triggered immunity (MTI) research has traditionally centred around signal transduction pathways originating from activated membrane-localized pattern recognition receptors (PRRs), culminating in nuclear transcription and posttranslational modifications. More recently, chloroplasts have emerged as key immune signalling hubs, playing a central role in integrating environmental signals. Notably, MAMP recognition induces chloroplastic reactive oxygen species (cROS) that is suppressed by pathogen effectors, which also modify the balance of chloroplast-synthesized precursors of the defence hormones, jasmonic acid, salicylic acid (SA) and abscisic acid. This study focuses on how well-characterized PRRs and coreceptors modulate chloroplast physiology, examining whether diverse signalling pathways converge to similarly modulate chloroplast function. Pretreatment of receptor mutant plants with MAMP and D(Damage)AMP peptides usually protect against effector modulation of chlorophyll fluorescence and prevent Pseudomonas syringae effector-mediated quenching of cROS and suppression of maximum dark-adapted quantum efficiency (the ratio of variable/maximum fluorescence [Fv /Fm ]). The MTI coreceptor double mutant, bak1-5/bkk1-1, exhibits a remarkable decrease in Fv /Fm compared to control plants during infection, underlining the importance of MTI-mediated signalling in chloroplast immunity. Further probing the role of the chloroplast in immunity, we unexpectedly found that even moderate changes in light intensity can uncouple plant immune signalling.

Delayed death in the malaria parasite Plasmodium falciparum is caused by disruption of prenylation-dependent intracellular trafficking.

Apicomplexan parasites possess a plastid organelle called the apicoplast. Inhibitors that selectively target apicoplast housekeeping functions, including DNA replication and protein translation, are lethal for the parasite, and several (doxycycline, clindamycin, and azithromycin) are in clinical use as antimalarials. A major limitation of such drugs is that treated parasites only arrest one intraerythrocytic development cycle (approximately 48 hours) after treatment commences, a phenotype known as the 'delayed death' effect. The molecular basis of delayed death is a long-standing mystery in parasitology, and establishing the mechanism would aid rational clinical implementation of apicoplast-targeted drugs. Parasites undergoing delayed death transmit defective apicoplasts to their daughter cells and cannot produce the sole, blood-stage essential metabolic product of the apicoplast: the isoprenoid precursor isopentenyl-pyrophosphate. How the isoprenoid precursor depletion kills the parasite remains unknown. We investigated the requirements for the range of isoprenoids in the human malaria parasite Plasmodium falciparum and characterised the molecular and morphological phenotype of parasites experiencing delayed death. Metabolomic profiling reveals disruption of digestive vacuole function in the absence of apicoplast derived isoprenoids. Three-dimensional electron microscopy reveals digestive vacuole fragmentation and the accumulation of cytostomal invaginations, characteristics common in digestive vacuole disruption. We show that digestive vacuole disruption results from a defect in the trafficking of vesicles to the digestive vacuole. The loss of prenylation of vesicular trafficking proteins abrogates their membrane attachment and function and prevents the parasite from feeding. Our data show that the proximate cause of delayed death is an interruption of protein prenylation and consequent cellular trafficking defects.

Nonfreezing Cold Injury and Cold Intolerance in Paddlesport.

INTRODUCTION: Nonfreezing cold injury (NFCI) occurs when tissues are subjected to prolonged cooling that causes tissue damage, but not freezing. Long-term effects include cold intolerance, with allodynia, pain, or numbness of the affected limb. Those who participate in outdoor paddlesports are at particular risk. METHODS: This is an epidemiological study that aimed to determine the risk factors for paddlesport athletes developing NFCI and chronic cold intolerance in their hands. Secondary outcomes were to correlate cumulative cold exposure with the development of cold intolerance and to identify risk factors for developing NFCI or cold intolerance. Six hundred nine athletes responded to a survey distributed by their national governing body obtaining demographic and activity details, symptoms of NFCI, and a cold intolerance severity score (CISS). RESULTS: Twenty-three percent reported symptoms consistent with acute NFCI. The median CISS was 31 y (interquartile range 25-43), and 15% had a pathological CISS defined as >50. Females and individuals with Raynaud's phenomenon or migraines had a significantly higher CISS (P<0.05). Regression analysis found that females, smokers, and those with Raynaud's phenomenon or a previous nerve injury had a significantly higher risk of developing pathological cold intolerance (CISS >50). There was no correlation between cumulative cold exposure and CISS. CONCLUSIONS: A large proportion of paddlesport athletes undertaking activity in cold conditions have a pathological CISS or episodes consistent with NFCI. Cumulative cold exposure was not associated with a pathologically high CISS. The risk factors were female sex, smokers, and those suffering from either Raynaud's phenomenon or nerve injury.

Improved growth and morphological plasticity of Haloferax volcanii.

Some microbes display pleomorphism, showing variable cell shapes in a single culture, whereas others differentiate to adapt to changed environmental conditions. The pleomorphic archaeon Haloferax volcanii commonly forms discoid-shaped ('plate') cells in culture, but may also be present as rods, and can develop into motile rods in soft agar, or longer filaments in certain biofilms. Here we report improvement of H. volcanii growth in both semi-defined and complex media by supplementing with eight trace element micronutrients. With these supplemented media, transient development of plate cells into uniformly shaped rods was clearly observed during the early log phase of growth; cells then reverted to plates for the late log and stationary phases. In media prepared with high-purity water and reagents, without supplemental trace elements, rods and other complex elongated morphologies ('pleomorphic rods') were observed at all growth stages of the culture; the highly elongated cells sometimes displayed a substantial tubule at one or less frequently both poles, as well as unusual tapered and highly curved forms. Polar tubules were observed forming by initial mid-cell narrowing or tubulation, causing a dumbbell-like shape, followed by cell division towards one end. Formation of the uniform early log-phase rods, as well as the pleomorphic rods and tubules were dependent on the function of the tubulin-like cytoskeletal protein, CetZ1. Our results reveal the remarkable morphological plasticity of H. volcanii cells in response to multiple culture conditions, and should facilitate the use of this species in further studies of archaeal biology.

Chitin: A "Hidden Figure" in the Fungal Cell Wall.

Chitin and chitosan are two related polysaccharides that provide important structural stability to fungal cell walls. Often embedded deeply within the cell wall structure, these molecules anchor other components at the cell surface. Chitin-directed organization of the cell wall layers allows the fungal cell to effectively monitor and interact with the external environment. For fungal pathogens, this interaction includes maintaining cellular strategies to avoid excessive detection by the host innate immune system. In turn, mammalian and plant hosts have developed their own strategies to process fungal chitin, resulting in chitin fragments of varying molecular size. The size-dependent differences in the immune activation behaviors of variably sized chitin molecules help to explain how chitin and related chitooligomers can both inhibit and activate host immunity. Moreover, chitin and chitosan have recently been exploited for many biomedical applications, including targeted drug delivery and vaccine development.

Consolidating evidence on the effectiveness of interventions promoting fruit and vegetable consumption: an umbrella review.

BACKGROUND: The overarching objective was to examine the effectiveness of intervention strategies to promote fruit and vegetable consumption. To do this, systematic review evidence regarding the effects of intervention strategies was synthesized; organized, where appropriate, by the setting in which the strategies were implemented. Additionally, we sought to describe gaps in the review of evidence; that is, where evidence regarding the effectiveness of recommended policy actions had not been systematically synthesised. METHODS: We undertook a systematic search of electronic databases and the grey literature to identify systematic reviews describing the effects of any intervention strategy targeting fruit and/or vegetable intake in children or adults of any age. RESULTS: The effects of 32 intervention strategies were synthesised from the 19 included reviews. The strategies were mapped across all three broad domains of the NOURISHING framework (i.e. food environment, food system and behaviour change communication), but covered just 14 of the framework's 65 sub-policy areas. There was evidence supporting the effectiveness of 19 of the 32 intervention strategies. The findings of the umbrella review suggest that intervention strategies implemented within schools, childcare services, homes, workplaces and primary care can be effective, as can eHealth strategies, mass media campaigns, household food production strategies and fiscal interventions. CONCLUSIONS: A range of effective strategy options are available for policy makers and practitioners interested in improving fruit and/or vegetable intake. However, the effects of many strategies - particularly those targeting agricultural production practices, the supply chain and the broader food system - have not been reported in systematic reviews. Primary studies assessing the effects of these strategies, and the inclusion of such studies in systematic reviews, are needed to better inform national and international efforts to improve public health nutrition. TRIAL REGISTRATION: The review protocol was deposited in a publicly available Open Science framework prior to execution of the search strategy. https://osf.io/unj7x/.

Metabolic profiles of human brain parenchyma and glioma for rapid tissue diagnosis by targeted desorption electrospray ionization mass spectrometry.

Desorption electrospray ionization mass spectrometry (DESI-MS) is well suited for intraoperative tissue analysis since it requires little sample preparation and offers rapid and sensitive molecular diagnostics. Currently, intraoperative assessment of the tumor cell percentage of glioma biopsies can be made by measuring a single metabolite, N-acetylaspartate (NAA). The inclusion of additional biomarkers will likely improve the accuracy when distinguishing brain parenchyma from glioma by DESI-MS. To explore this possibility, mass spectra were recorded for extracts from 32 unmodified human brain samples with known pathology. Statistical analysis of data obtained from full-scan and multiple reaction monitoring (MRM) profiles identified discriminatory metabolites, namely gamma-aminobutyric acid (GABA), creatine, glutamic acid, carnitine, and hexane-1,2,3,4,5,6-hexol (abbreviated as hexol), as well as the established biomarker NAA. Brain parenchyma was readily differentiated from glioma based on these metabolites as measured both in full-scan mass spectra and by the intensities of their characteristic MRM transitions. New DESI-MS methods (5 min acquisition using full scans and MS/MS), developed to measure ion abundance ratios among these metabolites, were tested using smears of 29 brain samples. Ion abundance ratios based on signals for GABA, creatine, carnitine, and hexol all had sensitivities > 90%, specificities > 80%, and accuracies > 85%. Prospectively, the implementation of diagnostic ion abundance ratios should strengthen the discriminatory power of individual biomarkers and enhance method robustness against signal fluctuations, resulting in an improved DESI-MS method of glioma diagnosis.

A mixed-methods investigation to understand and improve the scaled-up infection prevention and control in primary care health facilities during the Ebola virus disease epidemic in Sierra Leone.

BACKGROUND: The 2014-2015 Ebola epidemic in West Africa became a humanitarian crisis that exposed significant gaps in infection prevention and control (IPC) capacity in primary care facilities in Sierra Leone. Operational partners recognized the national gap and rapidly scaled-up an IPC training and infrastructure package. This prompted us to carry out a mixed-methods research study which aimed to evaluate adherence to IPC practices and understand how to improve IPC at the primary care level, where most cases of Ebola were initially presenting. The study was carried out during the national peak of the epidemic. DISCUSSION: We successfully carried out a rapid response research study that produced several expected and unexpected findings that were used to guide IPC measures during the epidemic. Although many research challenges were similar to those found when conducting research in low-resource settings, the presence of Ebola added risks to safety and security of data collectors, as well as a need to balance research activities with the imperative of response to a humanitarian crisis. A participatory approach that attempted to unify levels of the response from community upwards helped overcome the risk of lack of trust in an environment where Ebola had damaged relations between communities and the health system. CONCLUSION: In the context of a national epidemic, research needs to be focused, appropriately resourced, and responsive to needs. The partnership between local academics and a humanitarian organization helped facilitate access to study sites and approvals that allowed the research to be carried out quickly and safely, and for findings to be shared in response forums with the best chance of being taken up in real-time.

Pregnant Women Have Poor Carbohydrate Knowledge and Do Not Receive Adequate Nutrition Education.

OBJECTIVES: In order to manage blood glucose levels in pregnancy, women need to know what and how much to eat, particularly for foods containing carbohydrate. The aim was to assess pregnant women's carbohydrate and standard serve size knowledge and examine whether health professionals provided nutrition education. METHODS: Between July 2017 and April 2018 Australian pregnant women were recruited to complete an online survey, including a modified PedCarbQuiz carbohydrate knowledge questionnaire and an online buffet, where they selected images equivalent to one Australian Guide to Healthy Eating (AGHE) standard serve size. RESULTS: 186 pregnant women (mean age 30.9 years, SD = 4.7 years) 12-22 weeks gestation completed the survey. Participants achieved a median score of 27/36 for identification of carbohydrate-containing foods and a median score of 1/12 (range 0-11) for identification of grams of carbohydrate in specific portions. Participants achieved a median score of 14/22 (range 4-19) for identification of one AGHE standard serve of 11 carbohydrate-containing foods. Less than half (n = 92, 49.5%) received nutrition education from health professionals. CONCLUSIONS FOR PRACTICE: Pregnant women had sub-optimal carbohydrate knowledge. This could contribute to impaired blood glucose concentrations and risk of adverse health outcomes in pregnancy. Opportunities for pregnant women to access nutrition advice from health professionals should be explored.

Dysregulation of bisphosphoglycerate mutase during in vitro maturation of oocytes.

PURPOSE: Oxygen is vital for oocyte maturation; however, oxygen regulation within ovarian follicles is not fully understood. Hemoglobin is abundant within the in vivo matured oocyte, indicating potential function as an oxygen regulator. However, hemoglobin is significantly reduced following in vitro maturation (IVM). The molecule 2,3-bisphosphoglycerate (2,3-BPG) is essential in red blood cells, facilitating release of oxygen from hemoglobin. Towards understanding the role of 2,3-BPG in the oocyte, we characterized gene expression and protein abundance of bisphosphoglycerate mutase (Bpgm), which synthesizes 2,3-BPG, and whether this is altered under low oxygen or hemoglobin addition during IVM. METHODS: Hemoglobin and Bpgm expression within in vivo matured human cumulus cells and mouse cumulus-oocyte complexes (COCs) were evaluated to determine physiological levels of Bpgm. During IVM, Bpgm gene expression and protein abundance were analyzed in the presence or absence of low oxygen (2% and 5% oxygen) or exogenous hemoglobin. RESULTS: The expression of Bpgm was significantly lower than hemoglobin when mouse COCs were matured in vivo. Following IVM at 20% oxygen, Bpgm gene expression and protein abundance were significantly higher compared to in vivo. At 2% oxygen, Bpgm was significantly higher compared to 20% oxygen, while exogenous hemoglobin resulted in significantly lower Bpgm in the COC. CONCLUSION: Hemoglobin and 2,3-BPG may play a role within the maturing COC. This study shows that IVM increases Bpgm within COCs compared to in vivo. Decreasing oxygen concentration and the addition of hemoglobin altered Bpgm, albeit not to levels observed in vivo.

Developing a Sound Body: Open Trial Results of a Group Healthy Lifestyle Intervention for Young Adults with Psychosis.

The mortality disparity for persons with schizophrenia spectrum disorders (SSDs) due to cardiovascular disease is a devastating problem. Many risk factors are present in young adults with psychosis that may be ameliorated with lifestyle interventions. Sixteen participants with SSDs enrolled in an 11-week open trial of a novel lifestyle intervention comprised of group high intensity interval training exercise and health and wellness education. The aims were to evaluate (1) feasibility and (2) impact on sedentary behavior, physical activity, nutritional knowledge, physiological outcomes, and psychological well-being at end of intervention and 11-week follow-up. Attendance rates were 70% or higher for both intervention components and participants reported increased learning about healthy eating and exercise habits. Moderate to large effect sizes were observed for physical activity and sedentary behavior with sustained improvements in sedentary behavior at follow-up. Meaningful changes were not observed in other domains.

Defining Success for A Declining Resource: Mental Models of Oyster Management in Apalachicola, Florida.

Wild oyster populations are in decline globally, affecting communities of generational fishers and changing the cultural dynamics of coastal communities. Managers have employed a range of approaches to conserve and restore oyster populations and sustainable fisheries; yet there is little agreement among managers, scientists, and resource users regarding what constitutes success. This study uses a qualitative, mental models approach to compare understandings of management, perceptions of management success, and barriers to achieving successful management outcomes among three critical stakeholder groups: natural resource managers, oyster harvesters, and aquaculture farmers. We found similarities among the mental models of all three groups in the causes and consequences of the oyster fishery decline, but major differences in definitions of management, factors needed for successful management, and barriers to success. This study takes a more comprehensive look at the understandings of stakeholders than previous research by mapping the causes and effects, from the decline of the oyster fishery to expectations of future success. Managers can improve stakeholder investment in management projects by gaining a better understanding of the differing definitions of project success, stakeholder participation, and stakeholder understanding of the role of management.