Blood volume reduction due to rapid plasma loss after birth in preterm piglets.

BACKGROUND: Understanding changes in blood volume after preterm birth is critical to preventing cardiovascular deterioration in preterm infants. The aims were to determine if blood volume is higher in preterm than term piglets and if blood volume changes in the hours after birth. METHODS: Paired blood volume measurements were conducted in preterm piglets (98/115d gestation, ~28wk gestation infant) at 0.5-5 h (n = 12), 0.5-9 h (n = 44) and 5-11 h (n = 7) after birth, and in a term cohort at 0.5-9 h (n = 40) while under intensive care. RESULTS: At 30 min after birth, blood volume was significantly lower in preterm piglets compared to term piglets. By 9 h after birth, blood volume had reduced by 18% in preterm piglets and 13% in term piglets. By 5-9 h after birth, preterm piglets had significantly lower blood volumes than at term (61 ± 10 vs. 76 ± 11 mL/kg). CONCLUSIONS: In contrast to clinical resources, preterm piglets have a lower blood volume than at term. Substantial reductions in blood volume after birth leave some preterm piglets hypovolemic. If this also occurs in preterm infants, this may have important clinical consequences. Modern studies of blood volume changes after birth are essential for improving preterm outcomes. IMPACT: Preterm piglets do not have a higher blood volume than their term counterparts, in contrast to current clinical estimates. Rapid reduction in blood volume after birth leads to hypovolemia in some preterm piglets. There is a critical need to understand blood volume changes after birth in preterm infants in order to improve clinical management of blood volume.

Evaluating clinical reasoning in first year DPT students using a script concordance test.

BACKGROUND: A script concordance test (SCT) provides a series of clinical vignettes to assess clinical reasoning in uncertainty. Appraised throughout health education literature, SCTs are cognitive assessments of clinical reasoning, though their use in Doctor of Physical Therapy (DPT) entry-level education has not been investigated. The purpose of this study was to develop and explore the reliability and validity of a SCT for first year DPT students. METHODS: The SCT was developed and implemented over four phases. During phases one and two, DPT program faculty consulted on course content from the first-year curriculum. Thirty clinical vignettes with three follow-up questions each were constructed. The SCT was pilot tested with five clinicians in phase three to assess question clarity. During phase four, the SCT was administered to students and a reference panel via Qualtrics. First year DPT students (n = 44) and reference panel physical therapists with at least two years of experience and advanced certification (n = 15) completed the SCT. Internal consistency was analyzed using Cronbach's Alpha. Differences between student and reference panel percent-correct scores were analyzed with a t-test. Relationships between student SCT scores and academic records were explored with Spearman's Rho. RESULTS: The SCT had an internal consistency of 0.74. A significant difference in scores was found between the students [mean 58.5 (+/-5.31)] and reference panel [65.8 (+/-4.88), p < .01]. No significant correlations between student SCT scores and academic records were found. CONCLUSIONS: The developed SCT was reliable and demonstrated satisfactory internal consistency among test items. The SCT successfully differentiated between groups, with the reference panel demonstrating statistically significant higher percent-correct scores compared to students. SCTs may provide means to measure clinical reasoning in DPT students and lead to novel pedagogical approaches to enhance clinical reasoning.

A test of Conserving Nature's Stage: protecting a diversity of geophysical traits can also support a diversity of species at a landscape scale.

Conserving Nature's Stage (CNS) is a concept from conservation planning that promotes the protection of areas encompassing a broad range of enduring geophysical traits to provide long-term habitat for diverse species. The efficacy of using enduring geophysical characteristics as surrogates for biodiversity, independent of non-geophysical features and when considering finer resolution area selections, has yet to be investigated. Here, we evaluated CNS using 33 fine-scale inventories of vascular plant, non-vascular plant, invertebrate or vertebrate species from 13 areas across three continents. For each inventory, we estimated a continuous multidimensional surrogate defined from topographic and soil estimates of the surveyed plots. We assessed surrogate effectiveness by comparing the species representation of surrogate selected plots to the representation from plots picked randomly and using species information. We then used correlation coefficients to assess the link between the performance and qualities of the inventories, surroundings and surrogates. The CNS surrogate showed positive performance for 24 of the 33 inventories, and among these tests, represented 28 more species than random and 83% of the total number of species on average. We also found a small number of weak correlations between performance and environmental variability, as well as qualities of the surrogate. Our study demonstrates that prioritizing areas for a variety of geophysical characteristics will, in most cases, promote the representation of species. Our findings also point to areas for future research that might enhance CNS surrogacy. This article is part of the Theo Murphy meeting issue 'Geodiversity for science and society'.

The status and future of essential geodiversity variables.

Rapid environmental change, natural resource overconsumption and increasing concerns about ecological sustainability have led to the development of 'Essential Variables' (EVs). EVs are harmonized data products to inform policy and to enable effective management of natural resources by monitoring global changes. Recent years have seen the instigation of new EVs beyond those established for climate, oceans and biodiversity (ECVs, EOVs and EBVs), including Essential Geodiversity Variables (EGVs). EGVs aim to consistently quantify and monitor heterogeneity of Earth-surface and subsurface abiotic features, including geology, geomorphology, hydrology and pedology. Here we assess the status and future development of EGVs to better incorporate geodiversity into policy and sustainable management of natural resources. Getting EGVs operational requires better consensus on defining geodiversity, investments into a governance structure and open platform for curating the development of EGVs, advances in harmonizing in situ measurements and linking heterogeneous databases, and development of open and accessible computational workflows for global digital mapping using machine-learning techniques. Cross-disciplinary collaboration and partnerships with governmental and private organizations are needed to ensure the successful development and uptake of EGVs across science and policy. This article is part of the Theo Murphy meeting issue 'Geodiversity for science and society'.

Floor-to-Stand Performance Among People Following Stroke.

OBJECTIVES: Studies have examined floor-to-stand performance in varied adult populations both quantitatively and qualitatively. Despite an elevated risk of falls and inability to independently return to stand after a fall, few have examined the ability to stand from the floor in patients recovering from stroke. There were 2 objectives of the study: to identify the relationships between floor-to-stand performance using a timed supine-to-stand test (TSS) and physical performance measures of gait, balance, and balance confidence among persons in the subacute phase after stroke; and to analyze descriptive strategies used in the completion of the TSS. METHODS: A cross-sectional design was implemented. Fifty-eight adults (mean age = 59.2 [standard deviation (SD) = 13.9] years; 34 [58.6%] men) who were in the subacute phase after ischemic or hemorrhagic stroke and who could stand from the floor with no more than supervision completed the TSS and physical performance assessments. RESULTS: The median time to complete the TSS in our sample was 13.0 (interquartile range = 15.5) seconds. TSS time was significantly correlated with physical performance tests, including the Timed "Up & Go" Test (ρ = 0.70), gait speed (ρ = -0.67), Dynamic Gait Index (ρ = -0.52), and Activities-Specific Balance Confidence Scale (ρ = -0.43). Thirty-two percent of the variance in TSS time was attributed to Timed "Up & Go" Test time and the use of the quadruped position to transition to standing. Participants who used a gait device were more likely to use a chair during rise to stand. CONCLUSION: The TSS demonstrates concurrent validity with physical performance measures. IMPACT: Findings serve to improve functional mobility examination after stroke and to formulate effective treatment interventions to improve floor-to-stand performance.

Operationalizing cultural adaptation to climate change: contemporary examples from United States agriculture.

It has been proposed that climate adaptation research can benefit from an evolutionary approach. But related empirical research is lacking. We advance the evolutionary study of climate adaptation with two case studies from contemporary United States agriculture. First, we define 'cultural adaptation to climate change' as a mechanistic process of population-level cultural change. We argue this definition enables rigorous comparisons, yields testable hypotheses from mathematical theory and distinguishes adaptive change, non-adaptive change and desirable policy outcomes. Next, we develop an operational approach to identify 'cultural adaptation to climate change' based on established empirical criteria. We apply this approach to data on crop choices and the use of cover crops between 2008 and 2021 from the United States. We find evidence that crop choices are adapting to local trends in two separate climate variables in some regions of the USA. But evidence suggests that cover cropping may be adapting more to the economic environment than climatic conditions. Further research is needed to characterize the process of cultural adaptation, particularly the routes and mechanisms of cultural transmission. Furthermore, climate adaptation policy could benefit from research on factors that differentiate regions exhibiting adaptive trends in crop choice from those that do not. This article is part of the theme issue 'Climate change adaptation needs a science of culture'.

A Systematic Appraisal of Conflicts of Interest and Researcher Allegiance in Clinical Studies of Dry Needling for Musculoskeletal Pain Disorders.

OBJECTIVE: The purpose of this study was to determine the frequency and methods of conflicts of interest (COI) reporting in published dry needling (DN) studies and to determine the frequency of researcher allegiance (RA). METHODS: A pragmatic systematic search was undertaken to identify DN studies that were included in systematic reviews. Information regarding COI and RA were extracted from the full text of the published DN reports, and study authors were sent a survey inquiring about the presence of RA. A secondary analysis also was undertaken based on study quality/risk of bias scores that were extracted from the corresponding systematic reviews and study funding extracted from each DN study. RESULTS: Sixteen systematic reviews were identified, containing 60 studies of DN for musculoskeletal pain disorders, 58 of which were randomized controlled trials. Of the DN studies, 53% had a COI statement. None of these studies disclosed a COI. Nineteen (32%) authors of DN studies responded to the survey. According to the RA survey, 100% of DN studies included at least 1 RA criterion. According to the data extraction, 1 RA criterion was met in 45% of the DN studies. The magnitude of RA per study was 7 times higher according to the surveys than in the published reports. CONCLUSION: These results suggest that COI and RA might be underreported in studies of DN. In addition, authors of DN studies might be unaware of the potential influence of RA on study results and conclusions. IMPACT: Improved reporting of COI/RA might improve credibility of results and help identify the various factors involved in complex interventions provided by physical therapists. Doing so could help optimize treatments for musculoskeletal pain disorders provided by physical therapists.

Post-acute immunological and behavioral sequelae in mice after Omicron infection.

Progress in understanding long COVID and developing effective therapeutics is hampered in part by the lack of suitable animal models. Here we used ACE2-transgenic mice recovered from Omicron (BA.1) infection to test for pulmonary and behavioral post-acute sequelae. Through in-depth phenotyping by CyTOF, we demonstrate that naïve mice experiencing a first Omicron infection exhibit profound immune perturbations in the lung after resolving acute infection. This is not observed if mice were first vaccinated with spike-encoding mRNA. The protective effects of vaccination against post-acute sequelae were associated with a highly polyfunctional SARS-CoV-2-specific T cell response that was recalled upon BA.1 breakthrough infection but not seen with BA.1 infection alone. Without vaccination, the chemokine receptor CXCR4 was uniquely upregulated on multiple pulmonary immune subsets in the BA.1 convalescent mice, a process previously connected to severe COVID-19. Taking advantage of recent developments in machine learning and computer vision, we demonstrate that BA.1 convalescent mice exhibited spontaneous behavioral changes, emotional alterations, and cognitive-related deficits in context habituation. Collectively, our data identify immunological and behavioral post-acute sequelae after Omicron infection and uncover a protective effect of vaccination against post-acute pulmonary immune perturbations.

Functional Degeneracy in Paracoccus denitrificans Pd1222 Is Coordinated via RamB, Which Links Expression of the Glyoxylate Cycle to Activity of the Ethylmalonyl-CoA Pathway.

Metabolic degeneracy describes the phenomenon that cells can use one substrate through different metabolic routes, while metabolic plasticity, refers to the ability of an organism to dynamically rewire its metabolism in response to changing physiological needs. A prime example for both phenomena is the dynamic switch between two alternative and seemingly degenerate acetyl-CoA assimilation routes in the alphaproteobacterium Paracoccus denitrificans Pd1222: the ethylmalonyl-CoA pathway (EMCP) and the glyoxylate cycle (GC). The EMCP and the GC each tightly control the balance between catabolism and anabolism by shifting flux away from the oxidation of acetyl-CoA in the tricarboxylic acid (TCA) cycle toward biomass formation. However, the simultaneous presence of both the EMCP and GC in P. denitrificans Pd1222 raises the question of how this apparent functional degeneracy is globally coordinated during growth. Here, we show that RamB, a transcription factor of the ScfR family, controls expression of the GC in P. denitrificans Pd1222. Combining genetic, molecular biological and biochemical approaches, we identify the binding motif of RamB and demonstrate that CoA-thioester intermediates of the EMCP directly bind to the protein. Overall, our study shows that the EMCP and the GC are metabolically and genetically linked with each other, demonstrating a thus far undescribed bacterial strategy to achieve metabolic plasticity, in which one seemingly degenerate metabolic pathway directly drives expression of the other. IMPORTANCE Carbon metabolism provides organisms with energy and building blocks for cellular functions and growth. The tight regulation between degradation and assimilation of carbon substrates is central for optimal growth. Understanding the underlying mechanisms of metabolic control in bacteria is of importance for applications in health (e.g., targeting of metabolic pathways with new antibiotics, development of resistances) and biotechnology (e.g., metabolic engineering, introduction of new-to-nature pathways). In this study, we use the alphaproteobacterium P. denitrificans as model organism to study functional degeneracy, a well-known phenomenon of bacteria to use the same carbon source through two different (competing) metabolic routes. We demonstrate that two seemingly degenerate central carbon metabolic pathways are metabolically and genetically linked with each other, which allows the organism to control the switch between them in a coordinated manner during growth. Our study elucidates the molecular basis of metabolic plasticity in central carbon metabolism, which improves our understanding of how bacterial metabolism is able to partition fluxes between anabolism and catabolism.

Universality and context-specificity in early executive function development.

A renewed interest in early executive function (i.e., EF or the conscious control of thought and behavior) development has led several research groups to suggest that EF may be emerging and is less coordinated (e.g., showing few relations between tasks) in the first few years (Devine et al., 2019; Gago Galvagno et al., 2021; Johansson et al., 2016; Miller & Marcovitch, 2015; Ribner et al., 2022). This potentially universal development in EF does not exclude the possibility that EF may also differ across context (e.g., Gago Galvagno et al., 2021; Lohndorf et al., 2019; Tran et al., 2015) reflecting unique strengths and development built within one's sociocultural environment. The present paper explores potential universal and context-specific early EF developments by focusing on three aims: (1) reviewing work on EF within the first two years of life that may speak to potential universality in the measurement, structure, growth, stability, and conceptualization of early EF (2) reviewing research that may speak to how the sociocultural context may play a role in context-specific development within early EF and (3) examining potential developmental EF frameworks for understanding universal and context-specific developments of early EF within context.

Parabolic avalanche scaling in the synchronization of cortical cell assemblies.

Neurons in the cerebral cortex fire coincident action potentials during ongoing activity and in response to sensory inputs. These synchronized cell assemblies are fundamental to cortex function, yet basic dynamical aspects of their size and duration are largely unknown. Using 2-photon imaging of neurons in the superficial cortex of awake mice, we show that synchronized cell assemblies organize as scale-invariant avalanches that quadratically grow with duration. The quadratic avalanche scaling was only found for correlated neurons, required temporal coarse-graining to compensate for spatial subsampling of the imaged cortex, and suggested cortical dynamics to be critical as demonstrated in simulations of balanced E/I-networks. The corresponding time course of an inverted parabola with exponent of χ = 2 described cortical avalanches of coincident firing for up to 5 s duration over an area of 1 mm2. These parabolic avalanches maximized temporal complexity in the ongoing activity of prefrontal and somatosensory cortex and in visual responses of primary visual cortex. Our results identify a scale-invariant temporal order in the synchronization of highly diverse cortical cell assemblies in the form of parabolic avalanches.

Exploring Delay to Follow-Up in a Rural Multidisciplinary Cleft Clinic.

BACKGROUND: Oral clefts require longitudinal multidisciplinary care with follow-up visits at regular intervals throughout a patient's childhood, and delayed care can be detrimental. Although loss to follow-up is commonly studied, this metric does not account for patients that do return to care, but months or years later than recommended. The aim of this study was to explore and determine risk factors for delay to follow-up (DTFU) in a cleft clinic at a rural academic center. METHODS: Medical records from the multidisciplinary cleft clinic at a single rural tertiary care institution between January 1, 2010, and December 31, 2019, were reviewed. The primary outcome was DTFU, measured as the difference in days between recommended and actual follow-up dates for a given visit. RESULTS: A cohort of 282 patients was analyzed, with a total of 953 visits. A total of 71% of patients experienced at least 1 delay in follow-up of 30 days or longer, and 50% had at least 1 delay of 90 days or longer. Out of all visits, the mean DTFU was 73 days (around 2.5 months). For 23% of patients, at least half their visits were delayed by more than 90 days, whereas 11% experienced a delay of more than 90 days with every visit. Patients who failed to show up to at least 1 appointment had significantly higher risk of DTFU ( P < 0.0001). Driving distance, driving time, SES, stage of cleft care, and cleft phenotype were not correlated with DTFU. For canceled appointments, 50.5% of recorded cancellation reasons were patient driven. CONCLUSIONS: Delay to follow-up in a multidisciplinary cleft clinic was prevalent in this rural cohort, with half of patients experiencing delays of 3 months or longer, and about 1 in 9 experiencing this delay with every visit. Delay to follow-up identifies patients with consistently high rates of delay in care, which could eventually lead to targeted interventions to increase compliance. Delay to follow-up may be a new and valuable measure of cleft care compliance that can be easily implemented by other institutions. Further investigation is needed to determine the relationship between delay and clinical outcomes in cleft patients.

An examination of Leapfrog safety measures and Magnet designation.

Leapfrog Hospital Safety Grades and Magnet designation are two publicly available measures that serve as proxies for health care quality and safety. We examine whether hospitals with a better rating in one Leapfrog safety measure also have favorable ratings in other Leapfrog safety measures and whether Magnet-designated hospitals have better Leapfrog safety scores related to outcomes, processes, and structures than non-Magnet hospitals. Our study found that hospital-associated infections (HAIs) were not strongly correlated with one another, but Leapfrog safety process and structural measures were significantly and strongly correlated with one another, suggesting hospitals that invest in processes/structures to improve quality tend to do so across many dimensions. Also, Magnet-designated hospitals had higher Leapfrog grades for structural measures but not systematically better infection rates. Only one HAI (central line-associated bloodstream infections) had lower rates in Magnet hospitals than non-Magnet hospitals. These analyses suggest that improvements in process and structural measures do not necessarily translate into lower HAIs. Hospitals may need specific quality improvement strategies to target each HAI since HAIs are not strongly correlated with one another. Future research is needed to identify what process and structural measures can decrease HAIs and how this should be reflected in Magnet designation evaluation criteria.

Cryptic Diversity of Black Band Disease Cyanobacteria in Siderastrea siderea Corals Revealed by Chemical Ecology and Comparative Genome-Resolved Metagenomics.

Black band disease is a globally distributed and easily recognizable coral disease. Despite years of study, the etiology of this coral disease, which impacts dozens of stony coral species, is not completely understood. Although black band disease mats are predominantly composed of the cyanobacterial species Roseofilum reptotaenium, other filamentous cyanobacterial strains and bacterial heterotrophs are readily detected. Through chemical ecology and metagenomic sequencing, we uncovered cryptic strains of Roseofilum species from Siderastrea siderea corals that differ from those on other corals in the Caribbean and Pacific. Isolation of metabolites from Siderastrea-derived Roseofilum revealed the prevalence of unique forms of looekeyolides, distinct from previously characterized Roseofilum reptotaenium strains. In addition, comparative genomics of Roseofilum strains showed that only Siderastrea-based Roseofilum strains have the genetic capacity to produce lasso peptides, a family of compounds with diverse biological activity. All nine Roseofilum strains examined here shared the genetic capacity to produce looekeyolides and malyngamides, suggesting these compounds support the ecology of this genus. Similar biosynthetic gene clusters are not found in other cyanobacterial genera associated with black band disease, which may suggest that looekeyolides and malyngamides contribute to disease etiology through yet unknown mechanisms.

Using an intensive interdisciplinary telehealth model to treat pediatric feeding disorders.

The necessity of treatment using telehealth was apparent during the novel coronavirus (COVID-19) pandemic, as many practitioners were forced to use telehealth as a primary mode of service delivery. Although the telehealth model has been studied for different populations, little is known about its success when applied with children with feeding disorders and complex medical histories. The purpose of this study was to evaluate the efficacy of using a telehealth model from the onset of treatment. All 5 children who participated engaged in low levels of acceptance and high levels of inappropriate mealtime behavior during baseline. Caregivers were taught to implement the treatment with high integrity using behavioral skills training. Procedural integrity increased posttraining, and as a result acceptance increased and inappropriate mealtime behavior decreased. Treatment gains maintained during follow up at 1 month and 1 year. These data are discussed in relation to alternative ways of providing treatment in locations where intensive feeding programs are not available.

Trends in Outcomes and Variation by Race and Ethnicity in Pediatric Plastic Surgery in the United States.

The American College of Surgeons' National Surgical Quality Improvement Project-Pediatric Data manages a multicenter dataset for monitoring outcomes in pediatric surgical care. We explored trends in outcomes in the most frequently sampled current procedural terminology codes related to craniofacial and cleft lip and palate (CLP) surgical procedures over a 7-year period. Methods: We used National Surgical Quality Improvement Project-Pediatric Data on 28,147 pediatric patients who underwent plastic surgical procedures between January 1, 2012, and December 31, 2018. Eighteen relevant current procedural terminology codes were selected and sorted into two procedure groups: CLP and craniofacial. For each group, we explored trends in readmission, reoperation, extended length of stay, morbidity, and racial and ethnic variation. Results: The proportion of readmissions following CLP repair saw a significant reduction per year (from 3.6% to 1.7%). African American or Black CLP patients had significantly higher rates of readmission and extended length of stay when compared to the overall cohort. Asian and White CLP patients had significantly lower rates of experiencing an extended length of stay. For craniofacial cases, extended length of stay decreased significantly per year (from 7.7% to 2.8%). One possible driver of this change was a decrease in transfusion rates during the study period from 59% to 47%. Conclusions: Pediatric CLP and craniofacial cases saw significant improvements in safety, as indicated by reductions in readmission and extended length of stay. Given the racial differences observed, especially among CLP patients, continued research to identify and address systems of racism in health care remains a priority.

Patient Experience with Virtual Preoperative Consultations in Pediatric Surgical Specialties.

BACKGROUND: A cross-sectional study was conducted to assess the comparative effectiveness of virtual visits for preoperative evaluation and surgical decision-making in three pediatric surgical subspecialties. METHODS: Patients who underwent surgical procedures in the departments of Urology, Ophthalmology, and Plastic and Oral Surgery at a tertiary care pediatric hospital over a one-year period during the COVID-19 pandemic were included. Patients were assigned to one of three clinical pathways based on their preoperative visit(s): only in-person visit(s) (IP), a combination of in-person and virtual visit(s) (IP/VV), and only virtual visit(s) (VV). Demographics, procedure information, and patient experience survey results were collected. We then assessed variations in procedure types and patient experience scores in these three patient groups. RESULTS: There were 431 patients who completed the modified patient experience survey. The most common procedures were circumcision (17%), excision of lesion (16%), and strabismus repair (11%). Survey results were positive, with 90% of participants rating that they would recommend the service to others. No significant differences were found among groups in their demographics, overall care rating, and duration between preoperative clinic visit and procedure. Post-hoc power analysis indicated 87% power to detect a 10% difference in survey ratings between IP and VV cases, confirming non-inferiority in patient satisfaction for virtual preoperative visits. CONCLUSION: This study demonstrated the non-inferiority of preoperative virtual visits in three pediatric surgical subspecialties as measured by patient experience scores. Additional studies with more granular scope are necessary to further elucidate telemedicine's safety and efficacy for select diagnoses. LEVEL OF EVIDENCE: III.

Firefighter Suicide: A Theoretical Model for a Population Specific Behavioral Autopsy Program.

Some research suggests that firefighters are possibly at greater risk than other at-risk first responder/public service populations for suicidality (e.g., police, Veterans, active duty military non-deployed males; Martin et al., 2017; Stanley et al., 2015; Stanley et al., 2016). Behavioral autopsies have been utilized to elucidate the clinical picture of other at-risk populations; however, to date there is no proposed or applied model for a suicide behavior autopsy in fire personnel. Developing a standardized suicide behavior autopsy will allow for a comprehensive understanding of firefighters who die by suicide and highlight potential areas for intervention. The aim of this paper is to integrate best practices for autopsy procedures from other high-risk populations into a comprehensive theoretical model for a proposed behavioral health autopsy for firefighters. Our recommended protocol is presented along with relevant limitations, clinical implications, and recommendations for future research.

Early evolution of glial morphology and inflammatory cytokines following hypoxic-ischemic injury in the newborn piglet brain.

Neuroinflammation is a hallmark of hypoxic-ischemic injury and can be characterized by the activation of glial cells and the expression of inflammatory cytokines and chemokines. Interleukin (IL)-1ß and tumor necrosis factor (TNF)α are among the best-characterized early response cytokines and are often expressed concurrently. Several types of central nervous system cells secrete IL-1ß and TNFα, including microglia, astrocytes, and neurons, and these cytokines convey potent pro-inflammatory actions. Chemokines also play a central role in neuroinflammation by controlling inflammatory cell trafficking. Our aim was to characterise the evolution of early neuroinflammation in the neonatal piglet model of hypoxic-ischemic encephalopathy (HIE). Piglets (< 24 h old) were exposed to HI insult, and recovered to 2, 4, 8, 12 or 24H post-insult. Brain tissue from the frontal cortex and basal ganglia was harvested for assessment of glial cell activation profiles and transcription levels of inflammatory markers in HI piglets with comparison to a control group of newborn piglets. Fluorescence microscopy was used to observe microglia, astrocytes, neurons, degenerating neurons and possibly apoptotic cells, and quantitative polymerase chain reaction was used to measure gene expression of several cytokines and chemokines. HI injury was associated with microglial activation and morphological changes to astrocytes at all time points examined. Gene expression analyses of inflammation-related markers revealed significantly higher expression of pro-inflammatory cytokines tumor necrosis factor-α (TNFα) and interleukin 1 beta (IL-1ß), chemokines cxc-chemokine motif ligand (CXCL)8 and CXCL10, and anti-inflammatory cytokine transforming growth factor (TGF)ß in every HI group, with some region-specific differences noted. No significant difference was observed in the level of C-X-C chemokine receptor (CCR)5 over time. This high degree of neuroinflammation was associated with a reduction in the number of neurons in piglets at 12H and 24H in the frontal cortex, and the putamen at 12H. This reduction of neurons was not associated with increased numbers of degenerating neurons or potentially apoptotic cells. HI injury triggered a robust early neuroinflammatory response associated with a reduction in neurons in cortical and subcortical regions in our piglet model of HIE. This neuroinflammatory response may be targeted using novel therapeutics to reduce neuropathology in our piglet model of neonatal HIE.

Five-Year Prospective Observational Study of African-American Men on Active Surveillance for Prostate Cancer Demonstrates Race Is Not Predictive of Oncologic Outcomes.

INTRODUCTION: This study aimed to evaluate if race impacted outcomes or risk of disease progression in men on active surveillance (AS) for prostate cancer. We present the results from our majority African-American cohort of men in an equal access setting over a 5-year follow-up period. PATIENTS AND METHODS: All patients who elected AS for prostate cancer at the Southeast Louisiana Veterans Health Care System are entered into a prospectively managed observational database. Patients were divided into groups based on self-reported race. Grade group progression was defined as pathologic upgrading above International Society of Urological Pathology Grade Group 1 disease on subsequent biopsies following diagnostic biopsy. All tests were 2 sided using a significance of .05. RESULTS: A total of 228 men met inclusion criteria in the study, including 154 non-Hispanic African American and 74 non-Hispanic Caucasian American men, with a median follow-up of 5 years from the initiation of AS. Race was not predictive of Gleason grade progression, AS discontinuation, or biochemical recurrence on Cox multivariate analysis (HR = 1.01, 0.94, 0.85, P = .96, .79, .81, respectively). On Kaplan-Meier analysis at 5 years, African-American progression-free, AS discontinuation free, and overall survival probability was comparable to their Caucasian American counterparts (P > .05 for all). CONCLUSIONS: Active surveillance is a safe treatment option for low and very low risk prostate cancer, regardless of race. African-American and Caucasian-American men did not have any significant difference in Gleason grade group progression in our cohort with 5-year follow-up.