TubULAR: tracking in toto deformations of dynamic tissues via constrained maps.

A common motif in biology is the arrangement of cells into tubes, which further transform into complex shapes. Traditionally, analysis of dynamic tissues has relied on inspecting static snapshots, live imaging of cross-sections or tracking isolated cells in three dimensions. However, capturing the interplay between in-plane and out-of-plane behaviors requires following the full surface as it deforms and integrating cell-scale motions into collective, tissue-scale deformations. Here, we present an analysis framework that builds in toto maps of tissue deformations by following tissue parcels in a static material frame of reference. Our approach then relates in-plane and out-of-plane behaviors and decomposes complex deformation maps into elementary contributions. The tube-like surface Lagrangian analysis resource (TubULAR) provides an open-source implementation accessible either as a standalone toolkit or as an extension of the ImSAnE package used in the developmental biology community. We demonstrate our approach by analyzing shape change in the embryonic Drosophila midgut and beating zebrafish heart. The method naturally generalizes to in vitro and synthetic systems and provides ready access to the mechanical mechanisms relating genetic patterning to organ shape change.

Monosynaptic inputs to ventral tegmental area glutamate and GABA co-transmitting neurons.

A unique population of ventral tegmental area (VTA) neurons co-transmits glutamate and GABA. However, the circuit inputs to VTA VGluT2+VGaT+ neurons are unknown, limiting our understanding of their functional capabilities. By coupling monosynaptic rabies tracing with intersectional genetic targeting in male and female mice, we found that VTA VGluT2+VGaT+ neurons received diverse brain-wide inputs. The largest numbers of monosynaptic inputs to VTA VGluT2+VGaT+ neurons were from superior colliculus, lateral hypothalamus, midbrain reticular nucleus, and periaqueductal gray, whereas the densest inputs relative to brain region volume were from dorsal raphe nucleus, lateral habenula, and ventral tegmental area. Based on these and prior data, we hypothesized that lateral hypothalamus and superior colliculus inputs were glutamatergic neurons. Optical activation of glutamatergic lateral hypothalamus neurons activated VTA VGluT2+VGaT+ neurons regardless of stimulation frequency and resulted in flee-like ambulatory behavior. In contrast, optical activation of glutamatergic superior colliculus neurons activated VTA VGluT2+VGaT+ neurons for a brief period of time at high stimulation frequency and resulted in head rotation and arrested ambulatory behavior (freezing). Stimulation of glutamatergic lateral hypothalamus neurons, but not glutamatergic superior colliculus neurons, was associated with VTA VGluT2+VGaT+ footshock-induced activity. In addition, inhibition of lateral hypothalamus glutamatergic neurons disrupted VTA VGluT2+VGaT+ tailshock-induced activity. We interpret these results such that inputs to VTA VGluT2+VGaT+ neurons may integrate diverse signals related to the detection and processing of motivationally-salient outcomes.Significance Statement VTA glutamate neurons have roles in motivated behavior and unique neurotransmission capabilities. A specific VTA glutamate neuron subtype, those that co-transmit glutamate and GABA, have unique outcome signaling properties compared to other VTA cell-types. However, the circuits that regulate these neurons are unclear. We identified the whole-brain inputs to VTA glutamate and GABA co-transmitting neurons. We also identify two distinct glutamatergic inputs that activate VTA glutamate and GABA co-transmitting neurons and result in different behavioral repertoires suggestive of threat processing. Together, these results provide novel insights into the circuit and cell-type specific influences on VTA glutamate and GABA co-transmitting neuronal activity as integrators of motivationally salient outcomes.

Higher Doses of Calcium Associated With Survival in Trauma Patients.

INTRODUCTION: Calcium is required for coagulation, cardiac output, and peripheral vascular resistance. Between 85% and 94% of trauma patients treated with massive blood transfusion develop hypocalcemia.1 The aim of this study is to evaluate the relationship between increased intravenous calcium administration during massive transfusion and improved survival of trauma patients. METHODS: We performed a retrospective analysis of trauma patients who received massive transfusion over a 2-y period. Doses of elemental calcium administered per unit of blood product transfused were calculated by calcium to blood product ratio (CBR). Chi-square test evaluated association between coagulopathy and 30-d mortality. Two-sample t-test evaluated association between CBR and coagulopathy. Bivariate regression analysis evaluated association between CBR and blood products transfused per patient. Multivariable logistic regression analysis, controlling for age, sex, coagulopathy, and Injury Severity Score evaluated the association between CBR and mortality. RESULTS: The study included 77 patients. Coagulopathy was associated with increased 30-d mortality (P < 0.05). Patients who survived had higher CBR than those who died (P < 0.05). CBR was associated with a significant reduction in total blood products transfused per patient (P < 0.05). CBR was not associated with coagulopathy (P = 0.24). Multivariable logistic regression analysis demonstrated that Injury Severity Score ≥16, coagulopathy and decreased CBR were significant predictors of mortality (P < 0.05). CBR above 50 mg was a predictor of survival (P < 0.05). CONCLUSIONS: Higher doses of calcium given per blood product transfused were associated with improved 30-d survival and decreased blood product transfusions.

Comparative analysis of thermal indices for modeling cold and heat stress in US dairy systems.

Quantifying the effect of thermal stress on milk yields is essential to effectively manage present and future risks in dairy systems. Despite the existence of numerous heat indices designed to communicate stress thresholds, little information is available regarding the accuracy of different indices in estimating milk yield losses from both cold and heat stress at large spatiotemporal scales. To address this gap, we comparatively analyzed the performance of existing thermal indices in capturing US milk yield response to both cold and heat stress at the national scale. We selected 4 commonly used thermal indices: the temperature-humidity index (THI), black globe humidity index (BGHI), adjusted temperature-humidity index (THIadj), and comprehensive climate index (CCI). Using a statistical panel regression model with observational and reanalysis weather data from 1981 to 2020, we systematically compared the patterns of yield sensitivities and statistical performance of the 4 indices. We found that the US state-level milk yield variability was better explained by the THIadj and CCI, which combine the effects of temperature, humidity, wind, and solar radiation. Our analysis also reveals continuous and nonlinear responses of milk yields to a range of cold to heat stresses across all 4 indices. This implies that solely relying on fixed thresholds of these indices to model milk yield changes may be insufficient to capture cumulative thermal stress. Cold extremes reduced milk yields comparably to those affected by heat extremes on the national scale. Additionally, we found large spatial variability in milk yield sensitivities, implying further limitations to the use of fixed thresholds across locations. Moreover, we found decreased yield sensitivity to thermal stress in the most recent 2 decades, suggesting adaptive changes in management to reduce weather-related risks.

Signs and Symptoms Clusters Among Patients With Acute Heart Failure: A Correlational Study.

BACKGROUND: Patients with acute heart failure present to the emergency department with a myriad of signs and symptoms. Symptoms evaluated in clusters may be more meaningful than those evaluated individually by clinicians. OBJECTIVE: Among emergency department patients, we aimed to identify signs and symptoms correlations, clusters, and differences in clinical variables between clusters. METHODS: Medical record data included adults older than 18 years, International Classification of Diseases, Tenth Revisions codes , and positive Framingham Heart Failure Diagnostic Criteria. Exclusion criteria included medical records with a ventricular assist device and dialysis. For analysis, correlation, and the Gower distance, the independent t test, Mann-Whitney U test, χ 2 test, and regression were performed. RESULTS: A secondary analysis was conducted from the data set to evaluate door-to-diuretic time among patients with acute heart failure in the emergency department. A total of 218 patients were included, with an average age of 69 ± 15 years and predominantly White (74%, n = 161). Two distinct symptom clusters were identified: severe and mild congestion. The severe congestion cluster had a more comorbidity burden compared with the mild congestion cluster, as measured by the Charlson Comorbidity index (cluster 1 vs cluster 2, 6 [5-7] vs 5 [4-6]; P = .0019). Heart failure with preserved ejection fraction was associated with the severe congestion symptom cluster ( P = .009), and heart failure with mildly reduced ejection fraction was associated with the mild congestion cluster ( P = .019). CONCLUSIONS: In conclusion, 2 distinct symptom clusters were identified among patients with acute heart failure. Symptom clusters may be related to ejection fraction or overall cardiac output and comorbidity burden.

Disparities in 30-Day Readmission Between Medicare/Medicaid and Private Insurance Among Patients With Heart Failure Screened for Cognitive Impairment.

BACKGROUND: Racial disparities exist among patients with heart failure (HF). HF is often comorbid with cognitive impairment. Appropriate self-care can prevent HF hospital readmissions but requires access to resources through insurance. Racial differences exist between insurance types, and this may influence the disparity between races and patients with HF and cognitive impairment. OBJECTIVE: The objectives of this study were to examine the relationships between insurance type and self-care stratified by race and to assess for differences in time-to-30-day readmission among patients with HF with cognitive impairment. METHODS: This is a secondary analysis of data collected among hospitalized patients with HF with cognitive impairment. Patients completed surveys on self-care (Self-Care of Heart Failure Index), HF knowledge (Dutch Heart Failure Knowledge Scale), depression (Geriatric Depression Scale), and social support (Enhancing Recovery in Coronary Heart Disease Social Support Inventory). Socioeconomic data were collected. Linear models were created to examine the relationships between insurance type and self-care by race. Kaplan-Meier curves and Cox regression were used to assess readmission. RESULTS: The sample of 125 patients with HF with cognitive impairment was predominantly Black (68%, n = 85) and male (53%, n = 66). The sample had either Medicare/Medicaid (62%, n = 78) or private insurance (38%, n = 47). Black patients with HF with cognitive impairment and private insurance reported higher self-care confidence compared with Black patients with HF with cognitive impairment and Medicare/Medicaid ( P < .05). Medicare/Medicaid was associated with a higher frequency of 30-day readmission and a faster time-to-readmission. CONCLUSIONS: Patients with HF with cognitive impairment and Medicare/Medicaid insurance reported lower self-care confidence and more likely to be readmitted within 30 days.

The implementation of a hepatitis C testing service in community pharmacies: I-COPTIC consensus statement.

OBJECTIVES: This aimed to develop a blueprint for an effective community pharmacy Hepatitis C virus (HCV) testing service by producing a consensus statement. STUDY DESIGN: This was a modified Delphi process. METHODS: We recruited a heterogenous panel of experts (who had been involved in the setup or delivery of a community pharmacy HCV testing service) by purposive and chain referral methods. We had three rounds of a modified Delphi process. The first was a series of questions with free text responses and was analysed using thematic analysis, and the second and third were statements for the respondents to rate using a 7-point Likert scale. Consensus was predefined in a published protocol, and the results were reviewed by a public and patient involvement panel before the statement was finalised. RESULTS: We had 24 participants, including community and hospital-based pharmacists, local pharmaceutical committee members, charity representatives (Hepatitis C Trust), local clinical service lead, nurse specialists and doctors. The response rate of the first, second and third rounds were 100%, 96% and 88%, respectively. After the third round, we had 60 statements that reached consensus. We discussed the accepted statements with a patient and public involvement group. We used these statements to produce the I-COPTIC statement and a graphical summary. CONCLUSIONS: We developed a blueprint for the design of a gold standard community pharmacy HCV testing service. We believe this will support the successful implementation of community pharmacy testing for HCV. Community pharmacy testing is an important service to help achieve and maintain HCV elimination.

A Comprehensive Review of Low-Intensity Focused Ultrasound Parameters and Applications in Neurologic and Psychiatric Disorders.

OBJECTIVES: Low-intensity focused ultrasound (LIFU) is gaining increased interest as a potential therapeutic modality for a range of neuropsychiatric diseases. Current neuromodulation modalities often require a choice between high spatial fidelity or invasiveness. LIFU is unique in this regard because it provides high spatial acuity of both superficial and deep neural structures while remaining noninvasive. This new form of noninvasive brain stimulation may provide exciting potential treatment options for a variety of neuropsychiatric disorders involving aberrant neurocircuitry within deep brain structures, including pain and substance use disorders. Furthermore, LIFU is compatible with noninvasive neuroimaging techniques, such as functional magnetic resonance imaging and electroencephalography, making it a useful tool for more precise clinical neuroscience research to further understand the central nervous system. MATERIALS AND METHODS: In this study, we provide a review of the most recent LIFU literature covering three key domains: 1) the history of focused ultrasound technology, comparing it with other forms of neuromodulation, 2) the parameters and most up-to-date proposed mechanisms of LIFU, and finally, 3) a consolidation of the current literature to date surrounding the clinical research that has used LIFU for the modification or amelioration of several neuropsychiatric conditions. RESULTS: The impact of LIFU including poststroke motor changes, pain, mood disorders, disorders of consciousness, dementia, and substance abuse is discussed. CONCLUSIONS: Although still in its infancy, LIFU is a promising tool that has the potential to change the way we approach and treat neuropsychiatric disorders. In this quickly evolving field, this review serves as a snapshot of the current understanding of LIFU in neuropsychiatric research.

Trends in NIH-funding to schools of nursing in the last 17 years.

BACKGROUND: Growing clinical demands, faculty retirements, fewer PhD-prepared graduates, and funding instability are challenges for nursing science. PURPOSE: The purpose of this analysis was to investigate National Institutes of Health (NIH) funding patterns in schools of nursing (SONs). METHODS: Data were extracted from the Blue Ridge Institute for Medical Research between 2006 and 2022. Growth modeling examined changes in funding over time between private and public SONs. DISCUSSION: In the last 17 years, NIH funding for SONs has risen nearly 25% but remains only 1% of the total NIH budget for extramural research. Overall, 109 (75%) of the SONs were public and 36 (25%) were private institutions. Regarding geography, 90% of the States received NIH funding except six: ID, ME, MS, NH, VT, and WY. Private SONs consistently received more funding than public SONs but the difference was only statistically significant in 2022. CONCLUSION: NIH funding has significantly increased to SONs, there is better geographic distribution but a funding disparity exists between public and private SONs.

Bed nucleus of the stria terminalis GABA neurons are necessary for changes in foraging behaviour following an innate threat.

Foraging is a universal behaviour that has co-evolved with predation pressure. We investigated the role of the bed nucleus of the stria terminalis (BNST) GABA neurons in robotic and live predator threat processing and their consequences in post-threat encounter foraging. Both robotic and live predator interactions increased BNST GABA neuron activity. Mice were trained to procure food in a laboratory-based foraging apparatus in which food pellets were placed at incrementally greater distances from a nest zone. After mice learned to forage, they were exposed to a robotic or live predator threat, while BNST GABA neurons were chemogenetically inhibited. Post-robotic threat encounter, mice spent more time in the nest zone, but other foraging parameters were unchanged compared with pre-encounter behaviour. Inhibition of BNST GABA neurons had no effect on foraging behaviour post-robotic threat encounter. Following live predator exposure, control mice spent significantly more time in the nest zone, increased their latency to successfully forage, and significantly altered their overall foraging performance. Inhibition of BNST GABA neurons during live predator exposure prevented changes in foraging behaviour from developing after a live predator threat. BNST GABA neuron inhibition did not alter foraging behaviour during robotic or live predator threats. We conclude that these results demonstrate that while both robotic and live predator encounters effectively intrude on foraging behaviour, the perceived risk and behavioural consequences of the threat are distinguishable. Additionally, BNST GABA neurons may play a role in the integration of prior innate predator threat experience that results in hypervigilance during post-encounter foraging behaviour.

Honeybees (Apis mellifera) decrease the fitness of plants they pollinate.

Most flowering plants require animal pollination and are visited by multiple pollinator species. Historically, the effects of pollinators on plant fitness have been compared using the number of pollen grains they deposit, and the number of seeds or fruits produced following a visit to a virgin flower. While useful, these methods fail to consider differences in pollen quality and the fitness of zygotes resulting from pollination by different floral visitors. Here we show that, for three common native self-compatible plants in Southern California, super-abundant, non-native honeybees (Apis mellifera L.) visit more flowers on an individual before moving to the next plant compared with the suite of native insect visitors. This probably increases the transfer of self-pollen. Offspring produced after honeybee pollination have similar fitness to those resulting from hand self-pollination and both are far less fit than those produced after pollination by native insects or by cross-pollination. Because honeybees often forage methodically, visiting many flowers on each plant, low offspring fitness may commonly result from honeybee pollination of self-compatible plants. To our knowledge, this is the first study to directly compare the fitness of offspring resulting from honeybee pollination to that of other floral visitors.

Ventral tegmental area glutamate neurons mediate nonassociative consequences of stress.

Exposure to trauma is a risk factor for the development of a number of mood disorders, and may enhance vulnerability to future adverse life events. Recent data demonstrate that ventral tegmental area (VTA) neurons expressing the vesicular glutamate transporter 2 (VGluT2) signal and causally contribute to behaviors that involve aversive or threatening stimuli. However, it is unknown whether VTA VGluT2 neurons regulate transsituational outcomes of stress and whether these neurons are sensitive to stressor controllability. This work adapted an operant mouse paradigm to examine the impact of stressor controllability on VTA VGluT2 neuron function as well as the role of VTA VGluT2 neurons in mediating transsituational stressor outcomes. Uncontrollable (inescapable) stress, but not physically identical controllable (escapable) stress, produced social avoidance and exaggerated fear in male mice. Uncontrollable stress in females led to exploratory avoidance of a novel brightly lit environment. Both controllable and uncontrollable stressors increased VTA VGluT2 neuronal activity, and chemogenetic silencing of VTA VGluT2 neurons prevented the behavioral sequelae of uncontrollable stress in male and female mice. Further, we show that stress activates multiple genetically-distinct subtypes of VTA VGluT2 neurons, especially those that are VGluT2+VGaT+, as well as lateral habenula neurons receiving synaptic input from VTA VGluT2 neurons. Our results provide causal evidence that mice can be used for identifying stressor controllability circuitry and that VTA VGluT2 neurons contribute to transsituational stressor outcomes, such as social avoidance, exaggerated fear, or anxiety-like behavior that are observed within trauma-related disorders.

Smell and Taste Disorders in Primary Care.

Disorders of smell and taste are reported by approximately one-fifth of people 40 years and older, and one-third of people 80 years and older. These disorders affect quality of life and the ability to identify smoke and toxins. Smell and taste disorders can be early signs of dementia or Parkinson disease and are associated with increased mortality. Dysfunction may be apparent or may develop insidiously. Screening questionnaires are available, but many patients are unaware of their disorder. Most smell and taste disorders are due to sinonasal disease but also could be caused by smoking, medications, head trauma, neurodegenerative disease, alcohol dependence, or less common conditions. The differential diagnosis should guide the evaluation and include anterior rhinoscopy and an examination of the oral cavity, head, and cranial nerves. Further investigation is often unnecessary, but nasal endoscopy and computed tomography of the sinuses may be helpful. Magnetic resonance imaging of the head with contrast should be performed if there is an abnormal neurologic examination finding or if trauma or a tumor is suspected. Olfactory testing is indicated in refractory cases or for patients with poor quality of life and disease associated with smell or taste dysfunction. Smell and taste disorders may resolve when reversible causes are treated, but improvement is less likely when they are due to trauma, age, or neurodegenerative disease. Olfactory training is a self-administered mindful exposure therapy that may improve olfactory function. Physicians should encourage patients to ensure that smoke and other alarms are operational and to adhere to food expiration dates.

The Use of Interactive Technology to Improve Student Accuracy on Electrocardiographic Interpretation.

ABSTRACT: Electrocardiography (ECG) instruction relies heavily on memorization of interpretation rules and lacks opportunities for hands-on practice. Consequently, nursing students struggle with ECG interpretation. In an online undergradute nursing course, we implemented interactive technology to facilitate kinesthetic pedagogy. Accuracy was evaluated at midterm and during final assessments by two experts using a standardized rubric. Students who engaged with interactive technology at both assessments demonstrated consistent accuracy of ECG interpretation; students who did not failed to demonstrate consistent accuracy with ECG interpretation. Incorporating interactive technology to facilitate psychomotor learning may be essential in improving the accuracy of ECG interpretation.

Neurochemical Signaling of Reward and Aversion to Ventral Tegmental Area Glutamate Neurons.

Ventral tegmental area (VTA) glutamate neurons signal and participate in reward and aversion-based behaviors. However, the neurochemical mechanisms that underlie how these neurons contribute to motivated behaviors is unknown. We used a combination of optical sensors to identify how distinct neurochemical inputs to VTA glutamate neurons participate in motivated behavior within female and male transgenic mice. Activity of glutamate inputs to VTA glutamate neurons increased for both reward-predicting and aversion-predicting cues and aversive outcomes, but subpopulations of glutamate inputs were increased or decreased by reward. For both reward and aversion-based cues and outcomes, activity of GABA inputs to VTA glutamate neurons mostly decreased. GCaMP recordings showed overall population increases in VTA glutamate neuron intracellular calcium during reward and aversion-based cues and outcomes. Electrophysiological recordings of VTA VGluT2 neurons showed that glutamate receptor activation increases firing while loss of excitation via glutamate receptor blockade decreases firing. GABA-A receptor activation decreased VTA glutamate neuron firing but GABA-A receptor blockade did not significantly change VTA glutamate neuron firing. Electrophysiological recordings in coordination with our sensor data suggest that glutamate inputs strongly regulate VTA glutamate neuron participation in diverse motivated behaviors.SIGNIFICANCE STATEMENT Glutamate and GABA are the primary excitatory and inhibitory neurotransmitters of the nervous system. However, identifying how these neurotransmitters regulate motivated behavior has remained challenging because of a lack of tools (1) capable of measuring neurotransmission at the temporal scale of motivated behaviors and (2) capable of capturing chemical signaling onto genetically-distinct neuronal populations. We have overcome these obstacles by implementing genetically-encoded fluorescent indicators to monitor both glutamate and GABA input dynamics exclusively to ventral tegmental area (VTA) glutamate neurons during reward and aversion-based behaviors. We identify that glutamate and GABA inputs to VTA glutamate neurons differentially and dynamically signal reward and aversion-based cues and outcomes. This research provides foundational evidence that links distinct neurotransmitters to motivated behaviors regulated by VTA glutamate neurons.

Metabolic design in a mammalian model of extreme metabolism, the North American least shrew (Cryptotis parva).

Mitochondrial adaptations are fundamental to differentiated function and energetic homeostasis in mammalian cells. But the mechanisms that underlie these relationships remain poorly understood. Here, we investigated organ-specific mitochondrial morphology, connectivity and protein composition in a model of extreme mammalian metabolism, the least shrew (Cryptotis parva). This was achieved through a combination of high-resolution 3D focused ion beam electron microscopy imaging and tandem mass tag mass spectrometry proteomics. We demonstrate that liver and kidney mitochondrial content are equivalent to the heart, permitting assessment of mitochondrial adaptations in different organs with similar metabolic demand. Muscle mitochondrial networks (cardiac and skeletal) are extensive, with a high incidence of nanotunnels - which collectively support the metabolism of large muscle cells. Mitochondrial networks were not detected in the liver and kidney as individual mitochondria are localized with sites of ATP consumption. This configuration is not observed in striated muscle, likely due to a homogeneous ATPase distribution and the structural requirements of contraction. These results demonstrate distinct, fundamental mitochondrial structural adaptations for similar metabolic demand that are dependent on the topology of energy utilization process in a mammalian model of extreme metabolism. KEY POINTS: Least shrews were studied to explore the relationship between metabolic function, mitochondrial morphology and protein content in different tissues. Liver and kidney mitochondrial content and enzymatic activity approaches that of the heart, indicating similar metabolic demand among tissues that contribute to basal and maximum metabolism. This allows an examination of mitochondrial structure and composition in tissues with similar maximum metabolic demands. Mitochondrial networks only occur in striated muscle. In contrast, the liver and kidney maintain individual mitochondria with limited reticulation. Muscle mitochondrial reticulation is the result of dense ATPase activity and cell-spanning myofibrils which require networking for adequate metabolic support. In contrast, liver and kidney ATPase activity is localized to the endoplasmic reticulum and basolateral membrane, respectively, generating a locally balanced energy conversion and utilization. Mitochondrial morphology is not driven by maximum metabolic demand, but by the cytosolic distribution of energy-utilizing systems set by the functions of the tissue.

Selection on dispersal drives evolution of metabolic capacities for energy production in female wing-polymorphic sand field crickets, Gryllus firmus.

Life history and metabolism covary, but the mechanisms and individual traits responsible for these linkages remain unresolved. Dispersal capability is a critical component of life history that is constrained by metabolic capacities for energy production. Conflicting relationships between metabolism and life histories may be explained by accounting for variation in dispersal and maximal metabolic rates. We used female wing-polymorphic sand field crickets, Gryllus firmus, selected either for long wings (LW, flight-capable) or short wings (SW, flightless) to test the hypothesis that selection on dispersal capability drives the evolution of metabolic capacities. While resting metabolic rates were similar, long-winged crickets reached higher maximal metabolic rates than short-winged crickets, resulting in improved running performance. We further provided insight into the mechanisms responsible for covariation between life history and metabolism by comparing mitochondrial content of tissues involved in powering locomotion and assessing the function of mitochondria isolated from long- and short-winged crickets. Our results demonstrated that larger metabolic capacities in long-winged crickets were underpinned by increases in mitochondrial content of dorsoventral flight muscle and enhanced bioenergetic capacities of mitochondria within the fat body, a tissue responsible for fuel storage and mobilization. Thus, selection on flight capability correlates with increases in maximal, but not resting metabolic rates, through modifications of tissues powering locomotion at the cellular and organelle levels. This allows organisms to meet high energetic demands of activity for life history. Dispersal capability should therefore explicitly be considered as a potential factor driving the evolution of metabolic capacities.

Delays in Door-to-Diuretic Time and 1-Year Mortality Among Patients With Heart Failure.

BACKGROUND: Achieving prompt euvolemic state in heart failure (HF) is associated with reduced mortality. Time-sensitive metrics such as door-to-diuretic time , or the time between presentation and administration of intravenous diuretics, may be an important facilitator of achieving a faster euvolemic state and reducing mortality. OBJECTIVE: The aim of this study was to investigate whether reduced door-to-diuretic time was associated with lower odds of death among hospitalized patients with HF. METHODS: A retrospective chart review of patients with HF admitted to a medical center was performed between 2020 and 2021. Inclusion criteria were an International Classification of Diseases, 10th Revision code for HF with positive Framingham Criteria and the use of intravenous bolus furosemide. Exclusion criteria included ventricular assist devices, dialysis, and ultrafiltration therapy. Data collected from the medical records included demographics, echocardiography, staff notes, and medications. The end point was 1-year all-cause mortality. Descriptive statistics, t tests or median test, and multivariate logistic regression were used to describe the sample, evaluate group differences, and determine odds of mortality, respectively. RESULTS: Among 160 charts from patients with HF (age, 70 ± 14.4 years; 52%, n = 83, male; 53%, n = 85, ischemic cardiomyopathy; 83%, n = 134, New York Heart Association classes III-IV), 30% (n = 48) died within 1 year. The median diuretic dose was 40 mg (interquartile range, 20 mg), with a median time of administration of 247 minutes (4.12 hours) (interquartile range, 294 minutes to 4.9 hours). After covariate adjustment, prolonged door-to-diuretic time more than doubled (2.22; 95% confidence interval, 1.03-4.8; P = .04) the odds of 1-year mortality. CONCLUSIONS: On the basis of this sample of charts from older highly symptomatic patients with HF, delayed door-to-diuretic time was associated with significantly greater odds of 1-year all-cause mortality.

Increased case-finding and uptake of direct-acting antiviral treatment essential for micro-elimination of hepatitis C among people living with HIV: a national record linkage study.

OBJECTIVES: Micro-elimination of hepatitis C virus (HCV) in people living with HIV (PLHIV) and co-infected with HCV has been proposed as a key contribution to the overall goal of HCV elimination. While other studies have examined micro-elimination in HIV-treated cohorts, few have considered HCV micro-elimination among those not treated for HIV or at a national level. METHODS: Through data linkage of national and sentinel surveillance data, we examined the extent of HCV testing, diagnosis and treatment among a cohort of PLHIV in Scotland identified through the national database of HIV-diagnosed individuals, up to the end of 2017. RESULTS: Of 5018 PLHIV, an estimated 797 (15%) had never been tested for HCV and 70 (9%) of these had undiagnosed chronic HCV. The odds of never having been tested for HCV were the highest in those not on HIV treatment [adjusted odds ratio (aOR) = 7.21, 95% confidence interval (CI): 5.15-10.10). Overall HCV antibody positivity was 11%, and it was at its highest among people who inject drugs (49%). Most of those with chronic HCV (91%) had attended an HCV treatment clinic but only half had been successfully treated (54% for those on HIV treatment, 12% for those not) by the end of 2017. The odds of never having been treated for HCV were the highest in those not on HIV treatment (aOR = 3.60, 95% CI: 1.59-8.15). CONCLUSIONS: Our data demonstrate that micro-elimination of HCV in PLHIV is achievable but progress will require increased effort to engage and treat those co-infected, including those not being treated for their HIV.