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Ryan L [...].

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Dengue virus (DENV) is a pathogenic arbovirus that causes human disease. The most severe stage of the disease (severe dengue) is characterized by vascular leakage, hypovolemic shock, and organ failure. Endothelial dysfunction underlies these phenomena, but the causal mechanisms of endothelial dysfunction are poorly characterized. This study investigated the role of c-ABL kinase in DENV-induced endothelial dysfunction. Silencing c-ABL with artificial miRNA or targeting its catalytic activity with imatinib revealed that c-ABL is required for the early steps of DENV infection. DENV-2 infection and conditioned media from DENV-infected cells increased endothelial expression of c-ABL and CRKII phosphorylation, promoted expression of mesenchymal markers, e.g., vimentin and N-cadherin, and decreased the levels of endothelial-specific proteins, e.g., VE-cadherin and ZO-1. These effects were reverted by silencing or inhibiting c-ABL. As part of the acquisition of a mesenchymal phenotype, DENV infection and treatment with conditioned media from DENV-infected cells increased endothelial cell motility in a c-ABL-dependent manner. In conclusion, DENV infection promotes a c-ABL-dependent endothelial phenotypic change that leads to the loss of intercellular junctions and acquisition of motility.

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Although the COVID-19 lockdowns in 2020 had some environmental benefits, the pandemic's impact on the global economy has also had conservation repercussions, especially in biodiverse nations. Ecuador, which is heavily reliant on petroleum, agricultural exports, and ecotourism, experienced a rise in poverty in response to pandemic shutdowns. In this study, we sought to quantify levels of illegal timber extraction and poaching before and after the start of COVID-19 lockdowns throughout two protected areas (Reserva Jama Coaque [JCR] and Bosque Seco Lalo Loor [BSLL]) in the endangered Pacific Forest of Ecuador. We analyzed chainsaw and gunshot acoustic data recorded from devices installed in the forest canopy from December 2019 to March 2020 and October 2020 to March 2021. Results from generalized linear mixed effects models indicated less chainsaw activity before lockdowns (ßpost.lockdown = 0.568 ± 0.266 SE, p-value = .030), although increased average rainfall also seemed to negatively affect chainsaw activity (ßavg.rainfall = -0.002 ± 0.0006 SE, p-value = .003). Gunshots were too infrequent to conduct statistical models; however, 87% of gunshots were detected during the 'lockdown' period. Observational data collected by rangers from these protected areas also noted an increase in poaching activities beginning mid to late 2020 and persisting into 2021. These results add to the steadily growing literature indicating an increase in environmental crime, particularly in biodiverse nations, catalyzed by COVID-19-related economic hardships. Identifying areas where environmental crime increased during pandemic lockdowns is vital to address both socioeconomic drivers and enforcement deficiencies to prevent further biodiversity loss and disease outbreaks and to promote ecosystem resilience. Our study also demonstrates the utility of passive acoustic monitoring to detect illegal resource extraction patterns, which can inform strategies such as game theory modeling for ranger patrol circuits and placement of real-time acoustic detection technologies to monitor and mitigate environmental crimes.

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OBJECTIVES: To define the prevalence of neurologic diagnoses and evaluate the utilization of critical care and neurocritical care (NCC) resources among children admitted to the PICU. DESIGN: Retrospective cohort analysis. SETTING: Data submitted to the Virtual Pediatric Systems (VPS) database. PATIENTS: All children entered in VPS during 2016 (January 1, 2016, to December 31, 2016). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 128,688 patients entered into VPS and were comprised of 24.3% NCC admissions and 75.7% general PICU admissions. The NCC cohort was older, represented more scheduled admissions, and was more frequently admitted from the operating room. The NCC cohort also experienced a greater decline in prehospitalization to posthospitalization functional status and required more frequent use of endotracheal intubation, arterial lines, and foley catheters but had an overall shorter duration of PICU and hospital length of stay with a higher mortality rate. One thousand seven hundred fifteen patients at 12 participating institutions were entered into a novel, pilot NCC module evaluating sources of secondary neurologic injury. Four hundred forty-eight patients were manually excluded by the data entrant, leaving 1,267 patients in the module. Of the patients in the module, 75.8% of patients had a NCC diagnosis as their primary diagnosis; they experienced a high prevalence of pathophysiologic events associated with secondary neurologic insult (ranging from hyperglycemia at 10.5% to hyperthermia at 36.8%). CONCLUSIONS: In children admitted to a VPS-contributing PICU, a diagnosis of acute neurologic disease was associated with greater use of resources. We have identified the most common etiologies of acute neurologic disease in the 2016 VPS cohort, and such admissions were associated with significant decrease in functional status, as well as an increase in mortality.

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Tarsometatarsal joint arthrodesis is a commonly accepted procedure for hallux valgus associated with severe deformity and first ray hypermobility or medial column instability. This study evaluates the correction of hallux valgus deformity and the maintenance of correction with and without the use of a stabilization screw between the first and second metatarsal bases. Through retrospective review of first tarsometatarsal joint arthrodesis within our institution we evaluated 63 patients. Twenty-seven patients did not have a first to second metatarsal base screw and were placed into the no screw cohort. Thirty-six patients did have a first to second metatarsal base screw and were placed into the screw cohort. This study population had an osseous union rate of 95%. Clinical and radiographic recurrence occurred in 5 of 63 patients (8%). At 1-y postop the measurements demonstrated that the screw cohort had an average intermetatarsal angle correction of 11.6 degrees while the no screw cohort had an average correction of 7.8 degrees. Additionally, at 1-y postop the screw cohort had greater maintenance of the intermetatarsal angle correction with an average change of 0.5 degrees compared to 2.3 degrees in the no screw cohort. We conclude that the addition of the stabilization screw improves the first tarsometatarsal joint arthrodesis construct resulting in a greater degree of realignment and maintenance of correction.

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Utilization of the talonavicular joint (TN) arthrodesis as an isolated procedure or in combination with hindfoot arthrodesis has been described in the literature for treatment of numerous hindfoot conditions. When used in isolation or with concomitant hindfoot arthrodesis, the TN joint has demonstrated nonunion rates reported as high as 37% in the literature. Despite previous research, there remains a lack of agreement upon the ideal fixation technique for TN joint arthrodesis with and without concomitant subtalar joint arthrodesis. The purpose of this study was to retrospectively compare the radiographic and clinical results of TN joint arthrodesis as part of double arthrodesis procedure utilizing 4 separate fixation constructs in the treatment of advanced hindfoot malalignment in stage III adult-acquired flatfoot deformity. We retrospectively reviewed 105 patients who underwent TN joint arthrodesis as part of double arthrodesis procedure utilizing 4 separate fixation constructs. Our results demonstrated a nonunion rate of 16.2%, with 17 nonunions identified within our patient population. One (2.4%) nonunion was observed in the 3-screw cohort, 7 (33.3%) nonunions were observed in the 2-screw cohort, 4 (16.0%) nonunions were observed in the 2-screw plus plate cohort, and 5 (29.4%) nonunions were observed in the 1-screw plus plate cohort. The difference in nonunion rate between the 4 cohorts was statistically significant. Based on these results, we conclude that the use of a 3-screw construct for TN joint arthrodesis as part of double arthrodesis procedure demonstrates a statistically significant reduction in nonunion rate and should be considered a superior fixation construct for this procedure.

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ABSTRACT Purpose: We aimed to assess failure rates of salvage interventions and changes in split kidney function (SKF) following failed primary repair of ureteropelvic junction obstruction (UPJO). Materials and Methods: A retrospective review of adult patients at an academic medical center who underwent salvage intervention following primary treatment for UPJO was performed. Symptomatic failure was defined as significant flank pain. Radiographic failure was defined as no improvement in drainage or a decrease in SKF by ≥7%. Overall failure, the primary outcome, was defined as symptomatic failure, radiographic failure, or both. Results: Between 2008-2017, 34 patients (median age 38 years, 50% men) met study criteria. UPJO management was primary pyeloplasty/secondary endopyelotomy for 21/34 (62%), primary pyeloplasty/secondary pyeloplasty for 6/34 (18%), and primary endopyelotomy/secondary pyeloplasty for 7/34 (21%). Median follow-up was 3.3 years following secondary intervention. Patients undergoing primary pyeloplasty/secondary endopyelotomy had significantly higher overall failure than those undergoing primary pyeloplasty/secondary pyeloplasty (16/21 [76%] vs. 1/6 [17%], p=0.015). Among patients undergoing secondary endopyelotomy, presence of a stricture on retrograde pyelogram, stricture length, and SKF were not associated with symptomatic, radiographic, or overall failure. Serial renography was performed for 28/34 (82%) patients and 2/28 (7%) had a significant decline in SKF. Conclusions: Following failed primary pyeloplasty, secondary endopyelotomy had a greater overall failure rate than secondary pyeloplasty. No radiographic features assessed were associated with secondary endopyelotomy failure. Secondary intervention overall failure rates were higher than reported in the literature. Unique to this study, serial renography demonstrated that significant functional loss was overall infrequent.

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PURPOSE: We aimed to assess failure rates of salvage interventions and changes in split kidney function (SKF) following failed primary repair of ureteropelvic junction obstruction (UPJO). MATERIALS AND METHODS: A retrospective review of adult patients at an academic medical center who underwent salvage intervention following primary treatment for UPJO was performed. Symptomatic failure was defined as significant flank pain. Radiographic failure was defined as no improvement in drainage or a decrease in SKF by ≥7%. Overall failure, the primary outcome, was defined as symptomatic failure, radiographic failure, or both. RESULTS: Between 2008-2017, 34 patients (median age 38 years, 50% men) met study criteria. UPJO management was primary pyeloplasty/secondary endopyelotomy for 21/34 (62%), primary pyeloplasty/secondary pyeloplasty for 6/34 (18%), and primary endopyelotomy/secondary pyeloplasty for 7/34 (21%). Median follow-up was 3.3 years following secondary intervention. Patients undergoing primary pyeloplasty/secondary endopyelotomy had significantly higher overall failure than those undergoing primary pyeloplasty/secondary pyeloplasty (16/21 [76%] vs. 1/6 [17%], p=0.015). Among patients undergoing secondary endopyelotomy, presence of a stricture on retrograde pyelogram, stricture length, and SKF were not associated with symptomatic, radiographic, or overall failure. Serial renography was performed for 28/34 (82%) patients and 2/28 (7%) had a significant decline in SKF. CONCLUSIONS: Following failed primary pyeloplasty, secondary endopyelotomy had a greater overall failure rate than secondary pyeloplasty. No radiographic features assessed were associated with secondary endopyelotomy failure. Secondary intervention overall failure rates were higher than reported in the literature. Unique to this study, serial renography demonstrated that significant functional loss was overall infrequent.

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NEW FINDINGS: What is the central question of this study? Herein, a methodological overview of our research team's (Global REACH) latest high altitude research expedition to Peru is provided. What is the main finding and its importance? The experimental objectives, expedition organization, measurements and key cohort data are discussed. The select data presented in this manuscript demonstrate the haematological differences between lowlanders and Andeans with and without excessive erythrocytosis. The data also demonstrate that exercise capacity was similar between study groups at high altitude. The forthcoming findings from our research expedition will contribute to our understanding of lowlander and indigenous highlander high altitude adaptation. ABSTRACT: In 2016, the international research team Global Research Expedition on Altitude Related Chronic Health (Global REACH) was established and executed a high altitude research expedition to Nepal. The team consists of ∼45 students, principal investigators and physicians with the common objective of conducting experiments focused on high altitude adaptation in lowlanders and in highlanders with lifelong exposure to high altitude. In 2018, Global REACH travelled to Peru, where we performed a series of experiments in the Andean highlanders. The experimental objectives, organization and characteristics, and key cohort data from Global REACH's latest research expedition are outlined herein. Fifteen major studies are described that aimed to elucidate the physiological differences in high altitude acclimatization between lowlanders (n = 30) and Andean-born highlanders with (n = 22) and without (n = 45) excessive erythrocytosis. After baseline testing in Kelowna, BC, Canada (344 m), Global REACH travelled to Lima, Peru (∼80 m) and then ascended by automobile to Cerro de Pasco, Peru (∼4300 m), where experiments were conducted over 25 days. The core studies focused on elucidating the mechanism(s) governing cerebral and peripheral vascular function, cardiopulmonary regulation, exercise performance and autonomic control. Despite encountering serious logistical challenges, each of the proposed studies was completed at both sea level and high altitude, amounting to ∼780 study sessions and >3000 h of experimental testing. Participant demographics and data relating to acid-base balance and exercise capacity are presented. The collective findings will contribute to our understanding of how lowlanders and Andean highlanders have adapted under high altitude stress.

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Extreme inbreeding is expected to reduce the incidence of hybridization, serving as a prezygotic barrier. Mangrove rivulus is a small killifish that reproduces predominantly by self-fertilization, producing highly homozygous lines throughout its geographic range. The Bahamas and Caribbean are inhabited by two highly diverged phylogeographic lineages of mangrove rivulus, Kryptolebias marmoratus and a 'Central clade' closely related to K. hermaphroditus from Brazil. The two lineages are largely allopatric, but recently were found in syntopy on San Salvador, Bahamas, where a single hybrid was reported. To better characterize the degree of hybridization and the possibility of secondary introgression, here we conducted a detailed genetic analysis of the contact zone on San Salvador. Two mixed populations were identified, one of which contained sexually mature hybrids. The distribution of heterozygosity at diagnostic microsatellite loci in hybrids showed that one of these hybrids was an immediate offspring from the K. marmoratus x Central clade cross, whereas the remaining five hybrids were products of reproduction by self-fertilization for 1-3 generations following the initial cross. Two hybrids had mitochondrial haplotypes of K. marmoratus and the remaining four hybrids had a haplotype of the Central clade, indicating that crosses go in both directions. In hybrids, alleles of parental lineages were represented in equal proportions suggesting lack of recent backcrossing to either of the parental lineages. However, sympatric populations of two lineages were less diverged than allopatric populations, consistent with introgression. Results are discussed in terms of applicability of the biological species concept for isogenic, effectively clonal, organisms.

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