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Alzheimer’s disease (AD) is characterized by progressive accumulations of extracellular amyloid-beta (Aβ) aggregates from soluble oligomers to insoluble plaques and hyperphosphorylated intraneuronal tau, also from soluble oligomers to insoluble neurofibrillary tangles (NFTs). Tau and Aβ complexes spread from the entorhinal cortex of the brain to interconnected regions, where they bind pattern recognition receptors on microglia and astroglia to trigger inflammation and neurotoxicity that ultimately lead to neurodegeneration and clinical AD. Systemic inflammation is initiated by Aβ’s egress into the circulation, which may be secondary to microglial activation and can confer both destructive and reparative actions. Microglial activation pathways and downstream drivers of Aβ/NFT neurotoxicity, including inflammatory regulators, are primary targets for AD therapy. Osteopontin (OPN), an inflammatory cytokine and biomarker of AD, is implicated in Aβ clearance and toxicity, microglial activation, and inflammation, and is considered to be a potential therapeutic target. Here, using the most relevant works from the literature, we review and contextualize the evidence for a central role of OPN and associated inflammation in AD.

Blackpoll Warblers ( Setophaga striata ) have declined precipitously according to the North American Breeding Bird Survey, but that survey’s coverage of the boreal breeding range is limited. Migration monitoring offers an attractive tool for additional assessment because migrants from inaccessible portions of the breeding range are included in counts. However, for site-specific trends to be combined into regional or range-wide population trends, the breeding ground origin of the migrants counted at each site must be known. Blackpolls have a loop migration pattern in which spring and fall migrants follow different paths, but very little is known about population-specific routes within North America. We used stable hydrogen isotope assays of tail feathers ( δ 2 H f , 4th rectrix) and wing-length measurements from migration monitoring sites across Canada and the northeastern United States to broadly delineate breeding/natal origins of blackpolls captured at those sites. Blackpolls captured on spring migration in southern Ontario and western Quebec had characteristics expected of birds from breeding range west of the Great Lakes. These birds travel northward from the eastern Gulf of Mexico to Canada east of the Great Lakes before turning westward to reach their final destination between northwestern Ontario and eastern portions of the Northwest Territories. Many birds sampled at Great Lakes sites prior to 2010, but not thereafter, had δ 2 H f and wing-length characteristics expected of breeding range in eastern Canada, suggesting differential rates of population change among regions. Estimates of migratory connectivity indicated considerable mixing of populations from different portions of the breeding range during migration. Our results both corroborate and refine the known clockwise loop migration pattern, provide new insight into spring migration routes across North America, and provide a foundation for incorporating breeding ground origins into estimations of range-wide population trends based on standardized migration counts.

(1) Background: Adverse childhood experiences (ACEs), which are potentially traumatic childhood events, have been associated with increased tobacco product use. Less is known about electronic cigarette (e-cigarette) use during young adulthood. This study explored the associations between ACEs and current e-cigarette use among U.S. young adults. (2) Methods: This study was a secondary analysis of 2021 Behavioral Risk Factor Surveillance System data including 2537 young adults aged 18–24 years. Unadjusted and adjusted logistic regression analyses were conducted. (3) Results: Of the participants, 19.2% currently used e-cigarettes, and 22.1% reported 1 ACE, 13.0% reported 2 ACEs, 10.7% reported 3 ACEs, and 30.6% reported ≥4 ACEs. Unadjusted results indicated that participants who experienced 1 ACE (odds ratio (OR) = 1.76, 95% confidence interval (CI) = 1.01–3.07), 2 ACEs (OR = 2.18, 95%CI = 1.24–3.83), 3 ACEs (OR = 2.63, 95%CI = 1.41–4.90), and ≥4 ACEs (OR = 3.69, 95%CI = 2.23–6.09) were at increased odds of reporting current e-cigarette use than participants who experienced 0 ACEs. Adjusted results indicated that participants who experienced 3 ACEs were at 2.20 times higher odds (95%CI = 1.15–4.23) and participants who experienced ≥4 ACEs were at 2.73 times higher odds (95%CI = 1.58–4.71) of reporting current e-cigarette use than participants who experienced 0 ACEs. (4) Conclusions: Young adults exposed to ACEs are at risk of using e-cigarettes.

Probiotics have been investigated for many health benefits; however, few studies have been performed to determine the effects of oral probiotics on peripheral blood and respiratory immune cells in cattle. Our objectives were to determine changes in health and growth status, differential blood cell counts and function, and blood and lung cell function using flow cytometry and PCR in dairy calves fed a milk replacer with (PRO, N = 10) or without (CON, N = 10) the addition of probiotics to the milk replacer and dry rations from birth to weaning. Performance and clinical scores were not different between the treatment groups. Treatment-by-day interactions for peripheral blood leukocyte populations differed in cell number and percentages. A greater percentage of leukocytes expressed the cell surface markers CD3, CD4, CD8, CD11b, and CD205 on d 21 in CON animals. Lung lavages were performed on five animals from each treatment group on d 52. There were no differences between treatment groups for the expression of cytokines and Toll-Like Receptors as measured using Polymerase Chain Reaction, possibly due to the small sample size. Oral probiotics appear to affect peripheral blood immune cells and function. Their effect on overall calf health remains to be determined.

Estrogens have been implicated in the pathogenesis of various cancers, with increasing concern regarding the overall rising incidence of disease and exposure to environmental estrogens. Estrogens, both endogenous and environmental, manifest their actions through intracellular and plasma membrane receptors, named ERα, ERβ, and GPER. Collectively, they act to promote a broad transcriptional response that is mediated through multiple regulatory enhancers, including estrogen response elements (EREs), serum response elements (SREs), and cyclic AMP response elements (CREs). Yet, the design and rational assignment of antiestrogen therapy for breast cancer has strictly relied upon an endogenous estrogen–ER binary rubric that does not account for environmental estrogens or GPER. New endocrine therapies have focused on the development of drugs that degrade ER via ER complex destabilization or direct enzymatic ubiquitination. However, these new approaches do not broadly treat all cancer-involved receptors, including GPER. The latter is concerning since GPER is directly associated with tumor size, distant metastases, cancer stem cell activity, and endocrine resistance, indicating the importance of targeting this receptor to achieve a more complete therapeutic response. This review focuses on the critical importance and value of GPER-targeted therapeutics as part of a more holistic approach to the treatment of estrogen-driven malignancies.

Older individuals exhibiting diminished function of the locus coeruleus while learning new information show faster cognitive decline that is typical for Alzheimer’s disease.

Abstract Multi-compartment modelling of white matter microstructure using Neurite Orientation Dispersion and Density Imaging (NODDI) can provide information on white matter health through neurite density index and free water measures. We hypothesized that cerebrovascular disease, Alzheimer’s disease, and TDP-43 proteinopathy would be associated with distinct NODDI readouts of white matter damage which would be informative for identifying the substrate for cognitive impairment. We identified two independent cohorts with multi-shell diffusion MRI, amyloid and tau PET, and cognitive assessments: specifically, a population-based cohort of 347 elderly randomly sampled from the Olmsted county, Minnesota, population and a clinical research-based cohort of 61 amyloid positive Alzheimer’s dementia participants. We observed an increase in free water and decrease in neurite density using NODDI measures in the genu of the corpus callosum associated with vascular risk factors, which we refer to as the vascular white matter component. Tau PET signal reflective of 3R/4R tau deposition was associated with worsening neurite density index in the temporal white matter where we measured parahippocampal cingulum and inferior temporal white matter bundles. Worsening temporal white matter neurite density was associated with (antemortem confirmed) FDG TDP-43 signature. Post-mortem neuropathologic data on a small subset of this sample lend support to our findings. In the community-dwelling cohort where vascular disease was more prevalent, the NODDI vascular white matter component explained variability in global cognition (partial R2 of free water and neurite density = 8.3%) and MMSE performance (8.2%) which was comparable to amyloid PET (7.4% for global cognition and 6.6% for memory). In the AD dementia cohort, tau deposition was the greatest contributor to cognitive performance (9.6%), but there was also a non-trivial contribution of the temporal white matter component (8.5%) to cognitive performance. The differences observed between the two cohorts were reflective of their distinct clinical composition. White matter microstructural damage assessed using advanced diffusion models may add significant value for distinguishing the underlying substrate (whether cerebrovascular disease versus neurodegenerative disease caused by tau deposition or TDP-43 pathology) for cognitive impairment in older adults. Graphical abstract

Abstract Nuclear receptors (NR) are ligand-modulated transcription factors that regulate multiple cell functions and thus represent excellent drug targets. However, due to a considerable NR structural homology, NR ligands often interact with multiple receptors. Here, we describe a multiplex reporter assay (the FACTORIAL NR) that enables parallel assessment of NR ligand activity across all 48 human NRs. The assay comprises one-hybrid GAL4-NR reporter modules transiently transfected into test cells. To evaluate the reporter activity, we assessed their RNA transcripts. We used a homogeneous RNA detection approach that afforded equal detection efficacy and permitted the multiplex detection in a single-well format. For validation, we examined a panel of selective NR ligands and polypharmacological agonists and antagonists of the progestin, estrogen, PPAR, ERR, and ROR receptors. The assay produced highly reproducible NR activity profiles (r > 0.96) permitting quantitative assessment of individual NR responses. The inferred EC50 values agreed with the published data. The assay showed excellent quality ( = 0.73) and low variability ( = 7.2%). Furthermore, the assay permitted distinguishing direct and non-direct NR responses to ligands. Therefore, the FACTORIAL NR enables comprehensive evaluation of NR ligand polypharmacology.

Tobacco smoking is considered to be one of the main risk factors in the development of chronic pain. Long-term chronic exposure to nicotine and other forms of tobacco have been shown to be associated with an increased incidence of pain. Studies have shown that acupuncture can help smokers to reduce their desire to smoke, reduce their withdrawal symptoms, and avoid a relapse after treatment. However, little has been reported about the effects of acupuncture on pain sensitivity caused by long-term smoking. Models of hyperalgesia were established in rats exposed to nicotine for 6 weeks. After 6 weeks of continuous nicotine exposure, electroacupuncture at bilateral acupoints Zusanli (ST36) and Taichong (LR3) was performed 20 minutes per day for 6 days at a continuous wave with a frequency of 2 Hz and a stimulus intensity of 1 mA. The results revealed that electroacupuncture treatment increased the mechanical response threshold of hind paw of nicotine-dependent rats with hyperalgesia and up-regulated the protein expression of pain-related factors μ-opioid receptor, β-endorphin and glutamic acid decarboxylase 65 in the spinal cord and midbrain periaqueductal gray and the protein expression of glutamic acid decarboxylase 67 in the spinal cord. These findings suggest that electroacupuncture treatment has positive analgesic effects on pain sensitivity caused by long-term chronic nicotine exposure. One possible mechanism for the improved analgesia is that electroacupuncture increases the expression of pain-related factors in the spinal cord and midbrain periaqueductal gray. This study was approved by Institutional Animal Care and Use Committee (IACUC) of the University of Miami (#18-167) on December 12, 2018.

For over half a century, temperature wave was deemed exotic and mattered only at extremely low temperatures. Here, the authors reported direct observation of second sound, signature of the temperature wave, at a record-high temperature of over 200 K.

Background & Aims: Single-cell transcriptomics offer unprecedented resolution of tissue function at the cellular level, yet studies analyzing healthy adult human small intestine and colon are sparse. Here, we present single-cell transcriptomics covering the duodenum, jejunum, ileum, and ascending, transverse, and descending colon from 3 human beings. Methods: A total of 12,590 single epithelial cells from 3 independently processed organ donors were evaluated for organ-specific lineage biomarkers, differentially regulated genes, receptors, and drug targets. Analyses focused on intrinsic cell properties and their capacity for response to extrinsic signals along the gut axis across different human beings. Results: Cells were assigned to 25 epithelial lineage clusters. Multiple accepted intestinal stem cell markers do not specifically mark all human intestinal stem cells. Lysozyme expression is not unique to human Paneth cells, and Paneth cells lack expression of expected niche factors. Bestrophin 4 (BEST4)+ cells express Neuropeptide Y (NPY) and show maturational differences between the small intestine and colon. Tuft cells possess a broad ability to interact with the innate and adaptive immune systems through previously unreported receptors. Some classes of mucins, hormones, cell junctions, and nutrient absorption genes show unappreciated regional expression differences across lineages. The differential expression of receptors and drug targets across lineages show biological variation and the potential for variegated responses. Conclusions: Our study identifies novel lineage marker genes, covers regional differences, shows important differences between mouse and human gut epithelium, and reveals insight into how the epithelium responds to the environment and drugs. This comprehensive cell atlas of the healthy adult human intestinal epithelium resolves likely functional differences across anatomic regions along the gastrointestinal tract and advances our understanding of human intestinal physiology.

Insect species that are nectivorous as adults acquire essential fatty acids almost exclusively from host plants during larval development. Thus, as essential fatty acids are important for a number of different biological processes, adult allocation of this limited resource may result in important trade-offs. Most lepidopteran species that migrate do so as sexually immature adults, so essential fatty acids used for migratory flight would not be available for subsequent reproduction. Using the true armyworm, Mythimna unipuncta, as a model system we analyzed fat body samples to test the hypothesis that environmental cues would influence the use of essential fatty acids during migratory flight. We used diets manipulated isotopically to trace origins and use of stored lipids and used chromatographic analyses to determine fatty acid composition. In the first experiments, 5-day old moths that had been reared in summer or fall (migratory) conditions and were force flown for different lengths of time (0–6 h) after which samples of the fat body were analyzed. Rearing conditions did not affect fatty acid loading however patterns of use during flight differed with essential fatty acids being conserved under fall but not summer conditions. As migratory flight can take several days, we repeated the experiment when 5-day old moths were flown for 8 h each day for up to 5 days. Some moths were provided access to sugar water after each flight while others were only given water or only given sugar water once. When sugar water was readily or sporadically available, moths reared under fall conditions conserved their essential fatty acids indicating that the environmental cues responsible for the onset of migratory flight result in physiological changes that modify lipid use. However, when moths had only water, the essential fatty acids were not conserved, highlighting the importance of nectar availability at stopovers for the conservation essential fatty acids during migration. Isotopic analysis of the moth fat body indicated a large contribution of adult-derived diet to lipids used as fuel. The implications of using isotopic approaches to other flight studies and future research on differential resource allocation in winged monomorphic migratory insects are discussed. Summary statement: Isotopic tracing methods and gas chromatography were used to demonstrate that environmental cues can impact patterns of fatty acid use in true armyworm moths. In particular, essential fatty acids are conserved during migratory flight. However, availability of adult food sources will determine the degree to which essential fatty acids are conserved.

Background:. Depression is common in patients with chronic viral hepatitis. We evaluated the impact of major depressive disorder (MDD) and antidepressant use on survival among patients with HBV and HCV. Methods:. We used The Health Improvement Network database, the largest medical database in the UK, to identify incident HBV (n=1401) and HCV (n=1635) in patients between 1986 and 2017. Our primary composite outcome was the development of decompensated cirrhosis or death. MDD and each class of antidepressants were assessed in multivariate Cox proportional hazards models. Models were adjusted for age, sex, and clinical comorbidities. Results:. The prevalence of MDD among HCV patients was higher compared with HBV patients (23.5% vs. 9.0%, p0.001. MDD was not an independent predictor for decompensated cirrhosis-free survival or mortality. However, the use of tricyclic and tetracyclic antidepressants (TCAs) was associated with poor decompensated cirrhosis-free survival in HBV and HCV cohorts (adjusted HR: 1.80, 95% CI, 1.00–3.26 and 1.56, 95% CI, 1.13–2.14, respectively). Both TCAs in the HBV cohort and selective serotonin reuptake inhibitors among the HCV cohort were associated with poor overall survival (adjusted HR: 2.18, 95% CI, 1.16–4.10; 1.48, 95% CI, 1.02–2.16, respectively). Conclusions:. Although prevalent among viral hepatitis patients, MDD did not affect disease progression or survival in either HBV or HCV cohorts. TCA use was associated with poor decompensated cirrhosis-free survival. Therefore, its use should be further studied among viral hepatitis patients.

BackgroundThe last few years have seen major advances in blood biomarkers for Alzheimer's Disease (AD) with the development of ultrasensitive immunoassays, promising to transform how we diagnose, prognose, and track progression of neurodegenerative dementias.MethodsWe evaluated a panel of four novel ultrasensitive electrochemiluminescence (ECL) immunoassays against presumed CNS derived proteins of interest in AD in plasma [phosphorylated-Tau181 (pTau181), total Tau (tTau), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP)]. Two sets of banked plasma samples from the Massachusetts Alzheimer's Disease Research Center's longitudinal cohort study were examined: A longitudinal prognostic sample (n = 85) consisting of individuals with mild cognitive impairment (MCI) and 4 years of follow-up and a cross-sectional sample (n = 238) consisting of individuals with AD, other neurodegenerative diseases (OND), and normal cognition (CN).ResultsParticipants with MCI who progressed to dementia due to probable AD during follow-up had higher baseline plasma concentrations of pTau181, NfL, and GFAP compared to non-progressors. The best prognostic discrimination was observed with pTau181 (AUC = 0.83, 1.7-fold increase) and GFAP (AUC = 0.83, 1.6-fold increase). Participants with autopsy- and/or biomarker verified AD had higher plasma levels of pTau181, tTau and GFAP compared to CN and OND, while NfL was elevated in AD and further increased in OND. The best diagnostic discrimination was observed with pTau181 (AD vs CN: AUC = 0.90, 2-fold increase; AD vs. OND: AUC = 0.84, 1.5-fold increase) but tTau, NfL, and GFAP also showed good discrimination between AD and CN (AUC = 0.81–0.85; 1.5–2.2 fold increase).ConclusionsThese new ultrasensitive ECL plasma assays for pTau181, tTau, NfL, and GFAP demonstrated diagnostic utility for detection of AD. Moreover, the absolute baseline plasma levels of pTau181 and GFAP reflect cognitive decline over the next 4 years, providing prognostic information that may have utility in both clinical practice and clinical trial populations.

Individuals with acute and chronic traumatic brain injury (TBI) are associated with unique white matter (WM) structural abnormalities, including fractional anisotropy (FA) differences. Our research group previously used FA as a feature in a linear support vector machine (SVM) pattern classifier, observing high classification between individuals with and without acute TBI (i.e., an area under the curve [AUC] value of 75.50%). However, it is not known whether FA could similarly classify between individuals with and without history of chronic TBI. Here, we attempted to replicate our previous work with a new sample, investigating whether FA could similarly classify between incarcerated men with (n = 80) and without (n = 80) self-reported history of chronic TBI. Additionally, given limitations associated with FA, including underestimation of FA values in WM tracts containing crossing fibers, we extended upon our previous study by incorporating neurite orientation dispersion and density imaging (NODDI) metrics, including orientation dispersion (ODI) and isotropic volume (Viso). A linear SVM based classification approach, similar to our previous study, was incorporated here to classify between individuals with and without self-reported chronic TBI using FA and NODDI metrics as separate features. Overall classification rates were similar when incorporating FA and NODDI ODI metrics as features (AUC: 82.50%). Additionally, NODDI-based metrics provided the highest sensitivity (ODI: 85.00%) and specificity (Viso: 82.50%) rates. The current study serves as a replication and extension of our previous study, observing that multiple diffusion MRI metrics can reliably classify between individuals with and without self-reported history of chronic TBI.

Diabetic nephropathy (DN) is a polygenic disorder with few risk variants showing robust replication in large-scale genome-wide association studies. To understand the role of DNA methylation, it is important to have the prevailing genomic view to distinguish key sequence elements that influence gene expression. This is particularly challenging for DN because genome-wide methylation patterns are poorly defined. While methylation is known to alter gene expression, the importance of this causal relationship is obscured by array-based technologies since coverage outside promoter regions is low. To overcome these challenges, we performed methylation sequencing using leukocytes derived from participants of the Finnish Diabetic Nephropathy (FinnDiane) type 1 diabetes (T1D) study (n = 39) that was subsequently replicated in a larger validation cohort (n = 296). Gene body–related regions made up more than 60% of the methylation differences and emphasized the importance of methylation sequencing. We observed differentially methylated genes associated with DN in 3 independent T1D registries originating from Denmark (n = 445), Hong Kong (n = 107), and Thailand (n = 130). Reduced DNA methylation at CTCF and Pol2B sites was tightly connected with DN pathways that include insulin signaling, lipid metabolism, and fibrosis. To define the pathophysiological significance of these population findings, methylation indices were assessed in human renal cells such as podocytes and proximal convoluted tubule cells. The expression of core genes was associated with reduced methylation, elevated CTCF and Pol2B binding, and the activation of insulin-signaling phosphoproteins in hyperglycemic cells. These experimental observations also closely parallel methylation-mediated regulation in human macrophages and vascular endothelial cells.

Objective There is a substantial incidence of stroke in patients with atrial fibrillation (AF) not receiving anticoagulation. The reasons for not receiving anticoagulation are generally attributed to clinician’s choice, however, a proportion of AF patients refuse anticoagulation. The aim of our study was to investigate factors associated with patient refusal of anticoagulation and the clinical outcomes in these patients.Methods Our study population comprised patients in the Global Anticoagulant Registry in the FIELD (GARFIELD-AF) registry with CHA2DS2-VASc≥2. A logistic regression was developed with predictors of patient anticoagulation refusal identified by least absolute shrinkage and selection operator methodology. Patient demographics, medical and cardiovascular history, lifestyle factors, vital signs (body mass index, pulse, systolic and diastolic blood pressure), type of AF and care setting at diagnosis were considered as potential predictors. We also investigated 2-year outcomes of non-haemorrhagic stroke/systemic embolism (SE), major bleeding and all-cause mortality in patients who refused versus patients who received and patients who did not receive anticoagulation for other reasons.Results Out of 43 154 AF patients, who were at high risk of stroke, 13 283 (30.8%) did not receive anticoagulation at baseline. The reason for not receiving anticoagulation was unavailable for 38.7% (5146/13 283); of the patients with a known reason for not receiving anticoagulation, 12.5% (1014/8137) refused anticoagulation. Diagnosis in primary care/general practitioner, Asian ethnicity and presence of vascular disease were strongly associated with a higher risk of patient refusal of anticoagulation. Patient refusal of anticoagulation was associated with a higher risk of non-haemorrhagic stroke/SE (adjusted HR (aHR) 1.16 (95% CI 0.77 to 1.76)) but lower all-cause mortality (aHR 0.59 (95% CI 0.43 to 0.80)) compared with patients who received anticoagulation. The GARFIELD-AF mortality score corroborated this result.Conclusion The data suggest patient refusal of anticoagulation is a missed opportunity to prevent AF-related stroke. Further research is required to understand the patient profile and mortality outcome of patients who refuse anticoagulation.

Granulomas have been defined as inflammatory infiltrates formed by recruitment of macrophages and T cells. The three-dimensional spherical structure typically consists of a central core of tissue resident macrophages which may merge into multinucleated giant cells surrounded by T cells at the periphery. Granulomas may be triggered by infectious and non-infectious antigens. Cutaneous and visceral granulomas are common in inborn errors of immunity (IEI), particularly among patients with chronic granulomatous disease (CGD), combined immunodeficiency (CID), and common variable immunodeficiency (CVID). The estimated prevalence of granulomas in IEI ranges from 1%–4%. Infectious agents causing granulomas such Mycobacteria and Coccidioides presenting atypically may be ‘sentinel’ presentations for possible underlying immunodeficiency. Deep sequencing of granulomas in IEI has revealed non-classical antigens such as wild-type and RA27/3 vaccine-strain Rubella virus. Granulomas in IEI are associated with significant morbidity and mortality. The heterogeneity of granuloma presentation in IEI presents challenges for mechanistic approaches to treatment. In this review, we discuss the main infectious triggers for granulomas in IEI and the major forms of IEI presenting with ‘idiopathic’ non-infectious granulomas. We also discuss models to study granulomatous inflammation and the impact of deep-sequencing technology while searching for infectious triggers of granulomatous inflammation. We summarize the overarching goals of management and highlight the therapeutic options reported for specific granuloma presentations in IEI.

Irony seems lost on Michael Nahm in his preceding commentary on this summer’s adversarial exchange on the Bigelow Institute for Consciousness Studies (BICS) essay contest. For his commentary admonishes authors for misrepresenting others even while it engages in misrepresentation frequently and intentionally. Although Nahm characterizes my initial critique of the BICS essays unfavorably, in fact is it his preceding commentary that demonstrably falls short of “the standards of objectivity, impartiality and scientific responsibility required in academic debates” by repeatedly engaging in the very tactics that he rails against. The seven misrepresentations that Nahm accuses me of, on the other hand, amount to one minor mistake and six verifiably accurate characterizations of his BICS essay conclusions. Where it’s relevant to his commentary now, I will also occasionally address “what Augustine kept silent about” on Nahm’s contribution to the BICS competition. What I could’ve earlier exposed about his reasoning is not flattering, so Nahm should be careful what he wishes for. But he should take some solace in the fact that I lack the space to address the vast majority of his non sequiturs, sparing him further embarrassment.

All African felids are listed as vulnerable or endangered according to the IUCN (International Union for Conservation of Nature) Red List of Threatened Species. Cheetahs (Acinonyx jubatus) in particular have declined rapidly as a result of human impacts so that development of effective strategies and tools for conservation of this highly vulnerable species, as well as African felids in general, are essential for their survival in the wild. Here we use the oxygen stable isotopic compositions of cheetah hair to determine origins of cheetah cubs destined for the illegal exotic pet trade by associating individual cubs with predicted δ18O isoscape locations. We found that cheetah cubs most likely originated in East Africa, close to the corridors responsible for this aspect of the illegal wildlife trade to the Middle East. Further refinement of these assignments using a two isotope analysis (δ18O and δ13C values) indicate that these cubs were likely sourced in Southern Ethiopia or possibly as far as Tanzania. We also demonstrate that δ18O values in tissues can provide provenance information in cases where results of δ2H analyses may be obscured by the effects of metabolic routing of nutrients during nursing, starvation, or dehydration. This study demonstrates the utility of stable isotopic tools for conservation and forensic uses for endangered mammalian species.

Objective The objective of this study was to describe Ontario primary care teams’ experiences with collaboration during the COVID-19 pandemic. Descriptive qualitative methods using focus groups conducted virtually for data collection.Setting Primary care teams located in Ontario, Canada.Participants Our study conducted 11 focus groups with 10 primary care teams, with a total of 48 participants reflecting a diverse range of interprofessional healthcare providers and administrators working in primary care.Results Three themes were identified using thematic analysis: (1) prepandemic team functioning facilitated adaptation, (2) new processes of team interactions and collaboration, and (3) team as a foundation of support.Conclusions Results revealed the importance of collaboration for provider well-being, and the challenges of providing collaborative team-based primary care in the pandemic context. Caution against converting primary care collaboration to predominantly virtual modalities postpandemic is recommended. Further research on team functioning during the COVID-19 pandemic in other healthcare organisations will offer additional insight regarding how primary care teams can work collaboratively in a postpandemic environment.