Amplification of positivity for depression and anxiety: Neural prediction of treatment response.

Psychosocial treatments targeting the positive valence system (PVS) in depression and anxiety demonstrate efficacy in enhancing positive affect (PA), but response to treatment varies. We examined whether individual differences in neural activation to positive and negative valence incentive cues underlies differences in benefitting from a PVS-targeted treatment. Individuals with clinically elevated depression and/or anxiety (N = 88, ages 18 to 55) participated in one of two randomized, waitlist-controlled trials of Amplification of Positivity (AMP; NCT02330627, NCT03196544), a cognitive and behavioral intervention targeting the PVS. Participants completed a monetary incentive delay (MID) task during fMRI acquisition at baseline measuring neural activation to the possibility of gaining or losing money. Change in PA from before to after treatment was assessed using the Positive and Negative Affect Schedule. No significant associations were observed between baseline neural activation during gain anticipation and AMP-related changes in PA in regions of interest (striatum and insula) or whole-brain analyses. However, higher baseline striatal and insula activation during loss anticipation was associated with greater increases in PA post-AMP. This study provides preliminary evidence suggesting neural reactivity to negative valence cues may inform who stands to benefit most from treatments targeting the PVS.

Application of an egocentric social network approach to examine changes in social connections following treatment for anxiety and depression: A novel measurement tool for clinical trials research?

The epidemic of loneliness and social isolation has been recognized as a public health crisis warranting the same prioritization as other public health issues today, such as obesity, substance use disorders, and tobacco use. Social disconnection is particularly prevalent and disabling among individuals with anxiety and depression, yet it is inadequately evaluated and addressed in most clinical psychology treatment research. Studies generally employ global measures of perceived connectedness, loneliness, or relationship satisfaction, limiting understanding about elements of one's social network that may change with treatment. This study examined changes in the degree (number of people nominated) and quality of one's social network from pre-to post-treatment using an egocentric social network approach in 59 adults (mean age = 30.8 years, range = 18 to 54) with clinically elevated anxiety or depression who were randomized to a cognitive and behavioral positive valence treatment versus waitlist. Participants (egos) named people in their lives (alters) with whom they discussed important issues or spent free time. For each alter, participants rated how close they felt, how close they thought the alter felt to them, and how frequently they communicated. Linear regressions, which included treatment group as a predictor, revealed no group differences in changes in network degree, perceived alter feelings of closeness, or communication frequency, despite prior findings from this sample indicating larger increases in perceived global connectedness in the treatment group. Unexpectedly, the control group reported a greater increase in perceived closeness to alters. Post-hoc analyses revealed this was explained by the treatment group identifying more distal social ties (e.g., extended family, colleagues, roommates) as alters following treatment - an outcome positively associated with global improvements in connectedness. This proof-of-concept study suggests egocentric social network surveys may provide unique information on treatment-related changes in social functioning. Suggestions are provided for adaptations to facilitate application of social network surveys to mental health treatment research.

High Blood Pressure in Children Aged 3 to 12 Years Old With Overweight or Obesity.

Objective: (1) To describe the prevalence of high blood pressure (BP) and the association with BMI in young children with overweight/obesity; (2) to evaluate the accuracy of a single high BP to diagnose sustained hypertension over three visits. Methods: We used pre-intervention data from the Improving Pediatric Obesity Practice Using Prompts (iPOP-UP) trial. We included children aged 3-12 years with BMI ≥85th percentile at well-visits in 2019-2021 at 84 primary care practices in 3 US health systems in the Northeast, Midwest, and South. BP percentiles were calculated from the first visit with BP recorded during the study period. Hypertensive-range BP was defined by the 2017 American Academy of Pediatrics guideline. We tested the association between BMI classification and hypertensive BP using multivariable logistic regression. Results: Of 78,280 children with BMI ≥85th percentile, 76,214 (97%) had BP recorded during the study period (mean 7.4 years, 48% female, 53% with overweight, and 13% with severe obesity). The prevalence of elevated or hypertensive BP was 31%, including 27% in children with overweight and 33%, 39%, and 49% with class I, II, and III obesity, respectively. Higher obesity severity was associated with higher odds of hypertensive BP in the multivariable model. Stage 2 hypertensive BP at the initial visit had specificity of 99.1% (95% confidence interval 98.9-99.3) for detecting sustained hypertension over ≥3 visits. Conclusions: High BP is common in 3- to 12-year-olds with overweight/obesity, with higher obesity severity associated with greater hypertension. Children with overweight/obesity and stage 2 BP are likely to have sustained hypertension and should be prioritized for evaluation. Trial Registration: ClinicalTrials.gov Identifier: NCT05627011.

Nucleocytoplasmic transport rates are regulated by cellular processes that modulate GTP availability.

Nucleocytoplasmic transport (NCT), the facilitated diffusion of cargo molecules between the nucleus and cytoplasm through nuclear pore complexes (NPCs), enables numerous fundamental eukaryotic cellular processes. Ran GTPase uses cellular energy in the direct form of GTP to create a gradient across the nuclear envelope (NE) that drives the majority of NCT. We report here that changes in GTP availability resulting from altered cellular physiology modulate the rate of NCT, as monitored using synthetic and natural cargo, and the dynamics of Ran itself. Cell migration, cell spreading, and/or modulation of the cytoskeleton or its connection to the nucleus alter GTP availability and thus rates of NCT, regulating RNA export and protein synthesis. These findings support a model in which changes in cellular physiology that alter GTP availability can regulate the rate of NCT, impacting fundamental cellular processes that extensively utilize NCT.

The viscoelasticity of high concentration monoclonal antibodies using particle tracking microrheology.

The viscoelasticity of monoclonal antibodies (mAbs) is important during their production, formulation, and drug delivery. High concentration mAbs can provide higher efficacy therapeutics (e.g., during immunotherapy) and improved efficiency during their production (economy of scale during processing). Two humanized mAbs were studied (mAb-1 and mAb-2) with differing isoelectric points. Using high speed particle tracking microrheology, we demonstrated that the mAb solutions have significant viscoelasticities above concentrations of 40 mg/ml. Power law viscoelasticity was observed over the range of time scales (10-4-1 s) probed for the high concentration mAb suspensions. The terminal viscosity demonstrated an exponential dependence on mAb concentration (a modified Mooney relationship) as expected for charged stabilized Brownian colloids. Gelation of the mAbs was explored by lowering the pH of the buffer and a power law scaling of the gelation transition was observed, i.e., the exponent of the anomalous diffusion of the probe particles scaled inversely with the gelation time.

A core of cell wall proteins functions in wall integrity responses in Arabidopsis thaliana.

Cell walls surround all plant cells, and their composition and structure are tightly regulated to maintain cellular and organismal homeostasis. In response to wall damage, the cell wall integrity (CWI) system is engaged to ameliorate effects on plant growth. Despite the central role CWI plays in plant development, our current understanding of how this system functions at the molecular level is limited. Here, we investigated the transcriptomes of etiolated seedlings of mutants of Arabidopsis thaliana with defects in three major wall polysaccharides, pectin (quasimodo2), cellulose (cellulose synthase3 je5), and xyloglucan (xyloglucan xylosyltransferase1 and 2), to probe whether changes in the expression of cell wall-related genes occur and are similar or different when specific wall components are reduced or missing. Many changes occurred in the transcriptomes of pectin- and cellulose-deficient plants, but fewer changes occurred in the transcriptomes of xyloglucan-deficient plants. We hypothesize that this might be because pectins interact with other wall components and/or integrity sensors, whereas cellulose forms a major load-bearing component of the wall; defects in either appear to trigger the expression of structural proteins to maintain wall cohesion in the absence of a major polysaccharide. This core set of genes functioning in CWI in plants represents an attractive target for future genetic engineering of robust and resilient cell walls.

Young guard cells function dynamically despite low mechanical anisotropy but gain efficiency during stomatal maturation in Arabidopsis thaliana.

Stomata are pores at the leaf surface that enable gas exchange and transpiration. The signaling pathways that regulate the differentiation of stomatal guard cells and the mechanisms of stomatal pore formation have been characterized in Arabidopsis thaliana. However, the process by which stomatal complexes develop after pore formation into fully mature complexes is poorly understood. We tracked the morphogenesis of young stomatal complexes over time to establish characteristic geometric milestones along the path of stomatal maturation. Using 3D-nanoindentation coupled with finite element modeling of young and mature stomata, we found that despite having thicker cell walls than young guard cells, mature guard cells are more energy efficient with respect to stomatal opening, potentially attributable to the increased mechanical anisotropy of their cell walls and smaller changes in turgor pressure between the closed and open states. Comparing geometric changes in young and mature guard cells of wild-type and cellulose-deficient plants revealed that although cellulose is required for normal stomatal maturation, mechanical anisotropy appears to be achieved by the collective influence of cellulose and additional wall components. Together, these data elucidate the dynamic geometric and biomechanical mechanisms underlying the development process of stomatal maturation.

Tissue oxygen saturation is positively correlated with oxygen delivery and cardiac output in a canine hemorrhagic shock and resuscitation model.

OBJECTIVE: To determine if tissue oxygen saturation (StO2) correlates with oxygen delivery (DO2) and/or cardiac output (CO) in a canine hemorrhagic shock model. ANIMALS: 8 healthy purpose-bred dogs. METHODS: Dogs were anesthetized, and hemorrhagic shock was induced by withdrawing up to 60% of total blood volume, targeting a mean arterial pressure (MAP) of 40 mm Hg. The withdrawn blood was returned to the patient in 2 equal aliquots. Data was collected at 4 time points: 10 minutes after MAP was stabilized under anesthesia (time point [TP]-1), 10 minutes after up to 60% of blood volume was removed to target a MAP of 40 mm Hg (TP2), 10 minutes after the return of 50% of shed blood (TP3), and 10 minutes after the return of the remaining 50% of shed blood (TP4). Total blood volume withdrawn, StO2, CO, heart rate, and MAP were recorded, and DO2 was calculated at each TP. RESULTS: Mean StO2 significantly decreased between TP1 (77.8% [± 9.54]) and TP2 (44.8% [± 19.5]; P < .001 vs TP1). Mean StO2 increased to 63.1% (± 9.85) at TP3, but remained significantly lower compared to TP1 (P = .002). There was no difference between mean StO2 at TP4 (82.5% [± 12.6]) versus TP1 (P = .466). StO2 has a strong, positive correlation to both CO (r = 0.80; P < .001) and DO2 (r = 0.75; P < .001). CLINICAL RELEVANCE: A decrease in StO2 may be used in conjunction with physical examination findings and diagnostic parameters to support a diagnosis of shock. The return of shed blood was correlated with increases in StO2, DO2, and CO, suggesting that StO2 may be used as a marker of adequate resuscitation.

Trends in RSV testing patterns among infants presenting with bronchiolitis: Results from four United States health systems, 2015-2023.

BACKGROUND: Bronchiolitis due to respiratory syncytial virus (RSV) is the leading cause of hospitalization among American infants. The overall burden of RSV among infants has been historically under-estimated due to variable testing practices, particularly in the outpatient setting. Universal masking and social distancing implemented during the coronavirus disease 2019 (COVID-19) pandemic altered RSV seasonality, however potential consequences on RSV testing practices across different healthcare settings and sociodemographic groups have not been described. Variable testing practices could also affect accurate assessment of the effects of two recently approved RSV preventative agents targeting infants. METHODS: Utilizing real-time clinical and viral surveillance, we examined RSV testing practices among infants with bronchiolitis within four United States healthcare systems across different healthcare settings and sociodemographic groups pre- and post-COVID-19. RESULTS: RSV testing among infants with bronchiolitis increased since 2015 within each healthcare system across all healthcare settings and sociodemographic groups, with a more dramatic increase since the COVID-19 pandemic. Outpatient testing remained disproportionately low compared to hospital-based testing, although there were no major differences in testing frequency among sociodemographic groups in either setting. CONCLUSIONS: Although RSV testing increased among infants with bronchiolitis, relatively low outpatient testing rates remain a key barrier to accurate RSV surveillance.

Single-molecule tracking reveals dual front door/back door inhibition of Cel7A cellulase by its product cellobiose.

Degrading cellulose is a key step in the processing of lignocellulosic biomass into bioethanol. Cellobiose, the disaccharide product of cellulose degradation, has been shown to inhibit cellulase activity, but the mechanisms underlying product inhibition are not clear. We combined single-molecule imaging and biochemical investigations with the goal of revealing the mechanism by which cellobiose inhibits the activity of Trichoderma reesei Cel7A, a well-characterized exo-cellulase. We find that cellobiose slows the processive velocity of Cel7A and shortens the distance moved per encounter; effects that can be explained by cellobiose binding to the product release site of the enzyme. Cellobiose also strongly inhibits the binding of Cel7A to immobilized cellulose, with a Ki of 2.1 mM. The isolated catalytic domain (CD) of Cel7A was also inhibited to a similar degree by cellobiose, and binding of an isolated carbohydrate-binding module to cellulose was not inhibited by cellobiose, suggesting that cellobiose acts on the CD alone. Finally, cellopentaose inhibited Cel7A binding at micromolar concentrations without affecting the enzyme's velocity of movement along cellulose. Together, these results suggest that cellobiose inhibits Cel7A activity both by binding to the "back door" product release site to slow activity and to the "front door" substrate-binding tunnel to inhibit interaction with cellulose. These findings point to strategies for engineering cellulases to reduce product inhibition and enhance cellulose degradation, supporting the growth of a sustainable bioeconomy.

A Fracture Liaison Service to Address Vitamin D Deficiency for Patients Hospitalized for Osteoporotic Fracture.

Context: Addressing vitamin D deficiency (VDD) is important for fracture secondary prevention. Objectives: To explore the function of a fracture liaison service (FLS) to address VDD. Design Setting and Patients: An observational study of patients admitted to the Massachusetts General Hospital with fractures between January 1, 2016, and October 31, 2023, cared for by the FLS. Intervention: Ergocalciferol 50 000 international units (50ku-D2) oral daily for 3 to 7 days. Main Outcomes Measures: VDD prevalence. Efficacy of inpatient daily 50ku-D2 in raising serum 25-hydroxyvitamin D (25OHD) levels. Results: Of the 2951 consecutive patients, 724 (24.53%) had VDD (defined by 25OHD ≤ 19 ng/mL). Men (252/897, or 28.09%) were more likely than women (472/2054, or 22.98%) to have VDD (P = .003). VDD was seen in 41.79% (117/280), 24.41% (332/1360), and 20.98% (275/1311) of patients of aged ≤59, 60 to 79, and ≥80 years, respectively (P < .00001). Of the 1303 patients with hip fractures, 327 (25.09%) had VDD, which was associated with a longer length of stay (8.37 ± 7.35 vs 7.23 ± 4.78 days, P = .009) and higher trend of 30-day-readmission rate (13.63% vs 18.35%, P = .037). In a cohort of 32 patients with complete data, each dose of 50ku-D2 increased serum 25OHD by 3.62 ± 2.35 ng/mL without affecting serum calcium or creatinine levels. Conclusion: VDD was seen in nearly 25% of Massachusetts General Hospital FLS patients and more prevalent in male and younger patients. VDD was associated with longer length of stay and higher 30-day-readmission risk in patients with hip fracture. Daily 50ku-D2 appeared to be a practical way to quickly replete vitamin D in the inpatient setting.

Vulnerabilities in social anxiety: Integrating intra- and interpersonal perspectives.

What are the major vulnerabilities in people with social anxiety? What are the most promising directions for translational research pertaining to this condition? The present paper provides an integrative summary of basic and applied translational research on social anxiety, emphasizing vulnerability factors. It is divided into two subsections: intrapersonal and interpersonal. The intrapersonal section synthesizes research relating to (a) self-representations and self-referential processes; (b) emotions and their regulation; and (c) cognitive biases: attention, interpretation and judgment, and memory. The interpersonal section summarizes findings regarding the systems of (a) approach and avoidance, (b) affiliation and social rank, and their implications for interpersonal impairments. Our review suggests that the science of social anxiety and, more generally, psychopathology may be advanced by examining processes and their underlying content within broad psychological systems. Increased interaction between basic and applied researchers to diversify and elaborate different perspectives on social anxiety is necessary for progress.

Long-term efficacy and safety of cardiac genome editing for catecholaminergic polymorphic ventricular tachycardia.

Introduction: Heterozygous autosomal-dominant single nucleotide variants in RYR2 account for 60% of cases of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmia disorder associated with high mortality rates. CRISPR/Cas9-mediated genome editing is a promising therapeutic approach that can permanently cure the disease by removing the mutant RYR2 allele. However, the safety and long-term efficacy of this strategy have not been established in a relevant disease model. Aim: The purpose of this study was to assess whether adeno-associated virus type-9 (AAV9)-mediated somatic genome editing could prevent ventricular arrhythmias by removal of the mutant allele in mice that are heterozygous for Ryr2 variant p.Arg176Gln (R176Q/+). Methods and Results: Guide RNA and SaCas9 were delivered using AAV9 vectors injected subcutaneously in 10-day-old mice. At 6 weeks after injection, R176Q/+ mice had a 100% reduction in ventricular arrhythmias compared to controls. When aged to 12 months, injected R176Q/+ mice maintained a 100% reduction in arrhythmia induction. Deep RNA sequencing revealed the formation of insertions/deletions at the target site with minimal off-target editing on the wild-type allele. Consequently, CRISPR/SaCas9 editing resulted in a 45% reduction of total Ryr2 mRNA and a 38% reduction in RyR2 protein. Genome editing was well tolerated based on serial echocardiography, revealing unaltered cardiac function and structure up to 12 months after AAV9 injection. Conclusion: Taken together, AAV9-mediated CRISPR/Cas9 genome editing could efficiently disrupt the mutant Ryr2 allele, preventing lethal arrhythmias while preserving normal cardiac function in the R176Q/+ mouse model of CPVT.

The relationship between expressive suppression, therapeutic bond, and treatment outcomes of a positive affect intervention for adults with anxiety and/or depression.

Expressive suppression (ES; reducing emotional expression) is linked with reduced social connectedness in individuals with anxiety or depression. One implication is that people who use ES may have difficulty establishing a bond with their therapist which may impede clinical improvement. We examined this hypothesis in 33 adults with clinically elevated anxiety or depression receiving treatment focused on enhancing positive thoughts, emotions, and behaviors. At baseline, participants rated ES for positive and negative emotions during a standardized conversation task designed to generate connectedness. They also rated measures of early (session 3) perceived therapeutic bond and treatment outcomes (i.e. positive affect and social connectedness). ES of positive (r = -.39, p = .018), but not negative (r = .06, p = .747), emotions was negatively associated with therapeutic bond. Therapeutic bond mediated the relationship between greater ES of positive emotions during affiliation and lower post-treatment positive affect, 95% bias-corrected bootstrap confidence interval [-0.021, -0.000], adjusted for pre-treatment positive affect, as well as lower post-treatment social connectedness [-0.397, -0.015]; however, the indirect effect was not significant when accounting for pre-treatment social connectedness (p > .05). ES of positive emotions may be an important factor in the development of therapeutic bond and therefore treatment outcomes for individuals with anxiety or depression.

Adipose Tissue Analysis Toolkit (ATAT) for automated analysis of adipocyte size and extracellular matrix in white adipose tissue.

OBJECTIVE: The pathological expansion of white adipose tissue (WAT) in obesity involves adipocyte hypertrophy accompanied by expansion of the collagen-rich pericellular extracellular matrix (ECM) and development of crown-like structures (CLS). Traditionally, WAT morphology is assessed through immunohistochemical analysis of WAT sections. However, manual analysis of large histological sections is time-consuming, and the available digital tools for analyzing adipocyte size and pericellular ECM are limited. To address this gap, the authors developed the Adipose Tissue Analysis Toolkit (ATAT), an ImageJ plugin facilitating analysis of adipocyte size, WAT ECM, and CLS. METHODS AND RESULTS: ATAT utilizes local and image-level differentials in pixel intensity to independently threshold image background, distinguishing adipocyte-free tissue without user input. It accurately captures adipocytes in histological sections stained with common dyes and automates the analysis of adipocyte cross-sectional area, total-field, and localized region-of-interest ECM. ATAT allows fully automated batch analysis of histological images using default or user-defined adipocyte detection parameters. CONCLUSIONS: ATAT provides several advantages over existing WAT image analysis tools, enabling high-throughput analyses of adipocyte-specific parameters and facilitating the assessment of ECM changes associated with WAT remodeling due to weight changes and other pathophysiological alterations that affect WAT function.

A Population Pharmacokinetic Analysis of L-Glutamine Exposure in Patients with Sickle Cell Disease: Evaluation of Dose and Food Effects.

BACKGROUND AND OBJECTIVE: L-Glutamine is a treatment for children and adults with sickle cell disease. A comprehensive evaluation of the pharmacokinetics of L-glutamine in sickle cell disease has not been conducted. We aimed to assess the effects of long-term dosing, multiple dose levels, and food intake on L-glutamine exposure in patients with sickle cell disease compared to normal participants. METHODS: We conducted an open-label dose-ascending trial of L-glutamine in pediatric and adult participants with sickle cell disease (N = 8) and adult healthy volunteers (N = 4), providing a total of 400 plasma L-glutamine concentrations. Each participant received three ascending oral doses (0.1 and 0.3 g/kg twice daily and 0.6 g/kg once daily) over 3 weeks. Plasma L-glutamine concentrations were quantified using ion exchange chromatography. Both a non-compartmental pharmacokinetic analysis and a population pharmacokinetic analysis were performed. RESULTS: L-glutamine had rapid absorption and elimination, and there was no significant change in the baseline (pre-dose) L-glutamine concentration throughout the study, indicating no drug accumulation. Pharmacokinetics was best described by a one-compartment model with first-order kinetics. The dose-normalized peak concentration decreased with dose escalation, indicating the capacity-limited non-linear pharmacokinetics of oral L-glutamine. A covariate analysis showed that baseline L-glutamine concentrations correlated negatively with glutamine clearance, whereas dose positively correlated with volume of distribution. Food intake did not significantly affect glutamine clearance, indicating that L-glutamine can be taken with or without food. CONCLUSIONS: We report the first pharmacokinetic study of multiple-dose, long-term oral L-glutamine therapy and the first population pharmacokinetic analysis of L-glutamine for sickle cell disease. These findings may permit optimized dosing of L-glutamine for patients with sickle cell disease to maximize treatment benefits. CLINICAL TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (NCT04684381).

A quantitative survey of the blueberry (Vaccinium spp.) culturable nectar microbiome: variation between cultivars, locations, and farm management approaches.

Microbes in floral nectar can impact both their host plants and floral visitors, yet little is known about the nectar microbiome of most pollinator-dependent crops. In this study, we examined the abundance and composition of the fungi and bacteria inhabiting Vaccinium spp. nectar, as well as nectar volume and sugar concentrations. We compared wild V. myrsinites with two field-grown V. corymbosum cultivars collected from two organic and two conventional farms. Differences in nectar traits and microbiomes were identified between V. corymbosum cultivars but not Vaccinium species. The microbiome of cultivated plants also varied greatly between farms, whereas management regime had only subtle effects, with higher fungal populations detected under organic management. Nectars were hexose-dominant, and high cell densities were correlated with reduced nectar sugar concentrations. Bacteria were more common than fungi in blueberry nectar, although both were frequently detected and co-occurred more often than would be predicted by chance. "Cosmopolitan" blueberry nectar microbes that were isolated in all plants, including Rosenbergiella sp. and Symmetrospora symmetrica, were identified. This study provides the first systematic report of the blueberry nectar microbiome, which may have important implications for pollinator and crop health.

Ursids evolved dietary diversity without major alterations in metabolic rates.

The diets of the eight species of ursids range from carnivory (e.g., polar bears, Ursus maritimus) to insectivory (e.g., sloth bears, Melursus ursinus), omnivory (e.g., brown bears, U. arctos), and herbivory (e.g., giant pandas, Ailuropoda melanoleuca). Dietary energy availability ranges from the high-fat, highly digestible, calorically dense diet of polar bears (~ 6.4 kcal digestible energy/g fresh weight) to the high-fiber, poorly digestible, calorically restricted diet (~ 0.7) of giant pandas. Thus, ursids provide the opportunity to examine the extent to which dietary energy drives evolution of energy metabolism in a closely related group of animals. We measured the daily energy expenditure (DEE) of captive brown bears in a relatively large, zoo-type enclosure and compared those values to previously published results on captive brown bears, captive and free-ranging polar bears, and captive and free-ranging giant pandas. We found that all three species have similar mass-specific DEE when travel distances and energy intake are normalized even though their diets differ dramatically and phylogenetic lineages are separated by millions of years. For giant pandas, the ability to engage in low-cost stationary foraging relative to more wide-ranging bears likely provided the necessary energy savings to become bamboo specialists without greatly altering their metabolic rate.

Arterial blood gas measurements are different for brachycephalic and nonbrachycephalic dogs acclimatized to an altitude of 1,535 meters.

OBJECTIVE: To define reference intervals (RIs) for arterial blood gas (aBG) measurements in healthy, nonsedated, dolichocephalic, and mesocephalic (nonbrachycephalic) dogs at approximately 1,535 m above sea level and compare these findings with healthy, nonsedated, brachycephalic dogs living at the same altitude. ANIMALS: 120 adult nonbrachycephalic dogs and 20 adult brachycephalic dogs. METHODS: Cases were prospectively enrolled from October 2021 to June 2022. Dogs were enrolled from the community or after presentation for wellness examinations or minor injuries including lacerations, nail injuries, and lameness. Physical examinations and systolic blood pressure (sBP) measurements were obtained before blood sample collection. Arterial blood was collected from the dorsal pedal artery or femoral artery. After data collection, brachycephalic dogs underwent pre- and postexercise tolerance assessments. RESULTS: The mean and RI values for arterial pH (7.442; 7.375 to 7.515), partial pressure of oxygen in arterial blood (Pao2; 78.3; 59.2 to 92.7 mm Hg), partial pressure of carbon dioxide in arterial blood (Paco2; 28.0; 21.5 to 34.4 mm Hg), saturation of arterial oxygen (Sao2; 98.4; 84.3% to 101.4%), HCO3 (18.9; 14.9 to 22.4 mmol/L), concentration of total hemoglobin (ctHb; 17.5; 13.4 to 21.1 g/dL), and sBP (133; 94 to 180 mm Hg) were established for healthy nonbrachycephalic dogs at 1,535-m altitude. All aBG measurements were statistically and clinically different from those previously reported for dogs at sea level. Brachycephalic dogs had significantly lower Pao2 and Sao2 (P = .0150 and P = .0237, respectively) and significantly higher ctHb (P = .0396) compared to nonbrachycephalic dogs acclimatized to the same altitude; the nonbrachycephalic RIs were not transferable to the brachycephalic dogs for Pao2. CLINICAL RELEVANCE: This study represents the first collation of aBG measurements for healthy nonbrachycephalic dogs acclimatized to an altitude of 1,535 m. Additionally, this study identified differences in arterial oxygenation measurements between brachycephalic and nonbrachycephalic dogs. RIs in brachycephalic dogs need to be established.