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BACKGROUND: During the last years a great progress has been noted in device technology and operator experience in treating complex aortic aneurysms. Fenestrated and branched custom-made devices require detailed preoperative planning and production time that can take up to 12 weeks. During this awaiting period, the aortic related mortality is being increased. To overcome this limitation, off-the shelf standardized multibranched devices were launched in the market for the treatment of pararenal and thoracoabdominal aortic aneurysms (TAAA). Our aim was to systematically evaluate all the published studies of off-the shelf endografts for the treatment of pararenal and thoracoabdominal aortic aneurysms. METHODS: We performed a systematic review to identify all the eligible studies that reported outcomes to the off-the-shelf with inner or outer multibranched devices and then conducted a qualitative synthesis and meta-analysis of the results. The main outcomes were technical success, mortality, target visceral vessel (TVV) instability, major adverse events and reintervention rate. We estimated pooled proportions and 95% confidence intervals (CIs). RESULTS: A total of 1605 study titles were identified by the initial search strategy, of which 13 (8=t-Branch/ 3=E-nside/1=We-Flow/1=TAMBE) were considered eligible for inclusion in the meta-analysis. A total of 595 patients (70% male) were identified among the eligible studies. In terms of procedures, 64.4% were elective, 19.2% (13.4% outer-multibranched group (OMG); 6.1% inner-multibranched group (IMG) were emergent, and 16.4% (15.6% OMG; 0.8% IMG) were urgent. The pooled technical success was 92.1% (95%, CI, 83.8-96.4%) and 96.9% (95%, CI, 92.5-98.8%) for the outer- and inner-multibranched endograft, respectively. The pooled 30-day mortality was 10.4 % (95%, CI, 6.6-16.1%,) and 4.2% (95%, CI, 2.0-8.6%) for the outer and inner branched group respectively. The pooled 30-day and late TVV instability for the outer-branched group was 3.5% (95%, CI, 2.0-6.1%) and 6.2% (95%, CI, 4.7-8.0%) and for the inner branched group 10.4% (95%, CI, 4.5-22.5%) and 1.6% (95%, CI, 0.7-3.3%) respectively. CONCLUSIONS: This pooled analysis indicated good technical success and mortality rate, for both devices despite the high rate of urgent procedures. Pararenal and thoracoabdominal aortic aneurysms can be safely treated using the included devices. However, further studies are required to draw additional conclusions for the inner group due to the small sample size.
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Although the global conversion of wildlife habitat to built environments often has negative impacts on biodiversity, some wildlife species have the ability to cope by living in human-made structures. However, the determinants of this adaptation on a global scale are not well understood and may signify species with unique conservation needs at the human-wildlife interface. Here, we identify the trait profile associated with anthropogenic roosting in bats globally and characterize the evolution of this phenotype using an original dataset of roosting behavior developed across 1,279 extant species. Trait-based analyses showed that anthropogenic roosting is predictable across bats and is associated with larger geographic ranges, habitat generalism, temperate zone distributions, small litter and body size, and insectivory. We identified moderate phylogenetic signal in this complex trait profile, which has undergone both gains and losses across bat evolution and for which speciation rates are lower compared to natural roosting bats.
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[This corrects the article DOI: 10.3389/fchem.2024.1415644.].
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Cytochrome P450 2D6 (CYP2D6) is one of the most important enzymes involved in drug metabolism. Genetic polymorphism can influence drug metabolism by CYP2D6 such that a therapy is seriously affected by under- or overdosing of drugs. However, a general explanation at the atomistic level for poor activity is missing so far. Here we show for the 20 most common single nucleotide polymorphisms (SNPs) of CYP2D6 that poor metabolism is driven by four mechanisms. We found in extensive all-atom molecular dynamics simulations that the rigidity of the I-helix (central helix), distance between central phenylalanines (stabilizing bound substrate), availability of basic residues on the surface of CYP2D6 (binding of cytochrome P450 reductase), and position of arginine 132 (electron transfer to heme) are essential for an extensive function of the enzyme. These results were applied to SNPs with unknown effects, and potential SNPs that may lead to poor drug metabolism were identified. The revealed molecular mechanisms might be important for other drug-metabolizing cytochrome P450 enzymes.
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Citocromo P-450 CYP2D6 , Simulação de Dinâmica Molecular , Polimorfismo de Nucleotídeo Único , Citocromo P-450 CYP2D6/metabolismo , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/química , Humanos , Conformação ProteicaRESUMO
Bacteria are becoming increasingly resistant to antibiotics, therefore there is an urgent need for new classes of antibiotics to fight antibiotic resistance. Mammals do not express N É -acetyl-L-ornithine deacetylase (ArgE), an enzyme that is critical for bacterial survival and growth, thus ArgE represents a promising new antibiotic drug target, as inhibitors would not suffer from mechanism-based toxicity. A new ninhydrin-based assay was designed and validated that included the synthesis of the substrate analog N 5, N 5-di-methyl N α-acetyl-L-ornithine (kcat/Km = 7.32 ± 0.94 × 104 M-1s-1). This new assay enabled the screening of potential inhibitors that absorb in the UV region, and thus is superior to the established 214 nm assay. Using this new ninhydrin-based assay, captopril was confirmed as an ArgE inhibitor (IC50 = 58.7 µM; Ki = 37.1 ± 0.85 µM), and a number of phenylboronic acid derivatives were identified as inhibitors, including 4-(diethylamino)phenylboronic acid (IC50 = 50.1 µM). Selected inhibitors were also tested in a thermal shift assay with ArgE using SYPRO Orange dye against Escherichia coli ArgE to observe the stability of the enzyme in the presence of inhibitors (captopril Ki = 35.9 ± 5.1 µM). The active site structure of di-Zn EcArgE was confirmed using X-ray absorption spectroscopy, and we reported two X-ray crystal structures of E. coli ArgE. In summary, we describe the development of a new ninhydrin-based assay for ArgE, the identification of captopril and phenylboronic acids as ArgE inhibitors, thermal shift studies with ArgE + captopril, and the first two published crystal structures of ArgE (mono-Zn and di-Zn).
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OBJECTIVE: To evaluate sex based differences in ascending aorta and arch anatomy in patients with underlying proximal aortic disease and to evaluate their impact on feasibility for total endovascular repair with custom made, branched arch devices. METHODS: This was a retrospective cross sectional review of all patients undergoing open and or total endovascular arch repair due to distal ascending aorta and or aortic arch pathologies in a single high volume aortic centre between 2012 and 2022. Anatomical ascending aorta and aortic arch parameters were analysed on a flow centreline on a dedicated 3D workstation. Sex related differences of the ascending aorta, aortic arch, and supra-aortic vessels were evaluated. Subsequently, four endovascular devices were assessed for feasibility: double and triple branched devices both for the Zenith (Cook Medical) and Relay (Terumo Aortic) platforms, first in accordance with the instructions for use and then considering the possibility of adjunctive cervical debranching. The primary endpoints were sex specific differences in aortic anatomy, while secondary endpoints included sex based feasibility of branched endograft devices. RESULTS: During the study period, 395 patients underwent total aortic arch repair, of whom 152 (51 female, 33.5%) had high quality computed tomography angiograms available and were included in the study. Female patients had a shorter proximal landing zone than males (22 mm vs. 47 mm; p < .001). Left subclavian artery dissection was more frequent in men (24.8% vs. 3.9%; p < .001). Other anatomical parameters showed a similar distribution between sexes. Female patients presented a lower feasibility for double branched devices (35.3% vs. 58.4%; p = .015) as well as a tendency for lower feasibility rates for triple branched devices (31.4% vs. 47.5%; p = .081). CONCLUSION: Although most ascending aortic and arch parameters showed similar trends in both sexes, the availability of a suitable proximal landing zone was lower in female patients. Consequently, female patients had lower feasibility rates for double arch branched endografts and, to lesser extent, for triple arch branched endografts.
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Objective: Sutter Health launched system-wide general population standardized suicide screening with the Columbia-Suicide Severity Rating Scale (C-SSRS) screen (triage) version in 23 hospitals in 2019, replacing a one-question "danger to self" (DTS) assessment. This study analyzed the impact of C-SSRS implementation on screening rates, positive screenings, and documented psychiatric care within 90 days for all patients and a subgroup diagnosed with Major Depressive Disorder (MDD). Methods: Adults seen at hospitals in the pre-period (July 1, 2017-June 30, 2019) and post-period (July 1, 2019-December 31, 2020) were identified using electronic health records. Outcomes were compared using chi-square statistics and interrupted time series (ITS) models. Results: Pre-period, 92.8% (740,984/798,653) of patients were screened by DTS versus 84.6% (504,015/595,915) by C-SSRS in the post-period. Positive screening rates were 1.5% pre-period and 2.2% post-period, and 9.2% pre-period versus 10.8% post-period for those with MDD. Among individuals with positive screenings, 64.0% (pre-period) had documented follow-up psychiatric care versus 52.5% post-period and 66.4% of those with moderate or high-risk. Among all patients seen there was an overall increase in documentation of psychiatric care within 90 days (0.87% pre- to 0.96% post-period). ITS models revealed a 9.6% decline in screening, 1.3% increase in positive screenings, and 12.9% decline in documented psychiatric care following C-SSRS implementation (all p < 0.01). Conclusions: Following implementation, there was meaningful increase in suicide risk identification, and an increase in the proportion of patients with documented psychiatric care. Observed relative declines in screening warrant future research examining opportunities and barriers to general population C-SSRS use.
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BACKGROUND: In recent years the US health-care system has witnessed a substantial increase in telehealth use. Telehealth enhances health-care access and quality and may reduce costs. However, there is a concern that the shift from in-person to telehealth care delivery may differentially improve cancer care access and quality in certain clinical settings and for specific patient populations while potentially exacerbating disparities in care for others. Our National Cancer Institute-funded center, called Telehealth Research and Innovation for Veterans with Cancer (THRIVE), is focused on health equity for telehealth-delivered cancer care. We seek to understand how social determinants of telehealth-particularly race and ethnicity, poverty, and rurality-affect the use of telehealth. METHODS: THRIVE draws from the Health Disparities Research Framework and the Consolidated Framework for Implementation Research. THRIVE consists of multiple cores that work synergistically to assess and understand health equity for telehealth-delivered cancer care. These include the Administrative Core, Research and Methods Core, Clinical Practice Network, and Pragmatic Trial. RESULTS: As of October 2023, we identified and trained 5 THRIVE scholars, who are junior faculty beginning a research career. We have reviewed 20 potential pilot studies, funding 6. Additionally, in communication with our funders and advisory boards, we have adjusted our study design and analytic approach, ensuring feasibility while addressing our operational partners' needs. CONCLUSIONS: THRIVE has several key strengths. First, the Veterans Health Administration's health-care system is large and diverse regarding health-care setting type and patient population. Second, we have access to longitudinal data, predating the COVID-19 pandemic, about telehealth use. Finally, equitable access to high-quality care for all veterans is a major tenet of the Veterans Health Administration health-care mission. As a result of these advantages, THRIVE can focus on isolating and evaluating the impact of social determinants of telehealth on equity in cancer care.
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Neoplasias , Telemedicina , Veteranos , Humanos , Neoplasias/terapia , Neoplasias/epidemiologia , Estados Unidos/epidemiologia , Acessibilidade aos Serviços de Saúde , Disparidades em Assistência à Saúde , COVID-19/epidemiologia , United States Department of Veterans Affairs , Equidade em SaúdeRESUMO
BACKGROUND: Endovascular aortic repair (EVAR) has become the standard of care for patients with infrarenal aortic aneurysms over the last 2 decades. Endograft technology and treatment of complications like endoleaks, graft migration, or graft occlusion developed over time. However, sometimes open surgical conversion maybe required. Our aim was to analyze the indications, the technical aspects and outcomes in patients who underwent open conversion after EVAR with different types and generations of endografts. METHODS: This retrospective single-center study reviewed all patients who underwent EVAR from 2004 to 2020. Open surgical conversions >1 month post EVAR were identified. Conversions for graft infection were excluded. Indications for conversion and operative technique were analyzed. Primary endpoint of the study was 30-day mortality. Secondary endpoints were re-interventions and follow-up mortality. RESULTS: During 2004 and 2020, 443 consecutive EVARs were performed, and 28 patients required open surgical conversion, with an additional 3 referred from other hospitals (N = 31). The median age was 75 (range 58-93); 94% were male. Conversion was performed after a median time of 55 months (range 16-209). Twenty patients underwent elective and 11 emergency conversion. Indications for open conversion were graft migration, respectively, disease progression with endoleak type Ia and/or Ib in 52% (16/31) and sac expansion due to endoleak type II in 26% (8/31). Of the 31 patients, 17 (55%) had at least one previous endovascular re-intervention. All patients met the device-specific instructions for use for each implanted endograft. In-hospital intervention rate was 16% (5/31). Thirty-day mortality rate was 3% (1/31) with one patient died due to multiorgan failure after rupture with complete endograft replacement. Five patients (16%) died during follow-up. Mid-term follow-up was 47.5 months (range 24-203) with estimated cumulative survival rates of 97%, 89%, and 84%, at 1, 3, and 5 years, respectively. CONCLUSIONS: Late open conversion remains a valuable treatment option and can be performed safely in elective and emergency setting with a low early mortality. Lifelong surveillance and prompt intervention when necessary are essential in ensuring optimal outcomes after EVAR and preventing the need for emergent conversions.
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Aneurisma da Aorta Abdominal , Prótese Vascular , Conversão para Cirurgia Aberta , Correção Endovascular de Aneurisma , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Abdominal/mortalidade , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Conversão para Cirurgia Aberta/efeitos adversos , Endoleak/etiologia , Endoleak/cirurgia , Endoleak/mortalidade , Correção Endovascular de Aneurisma/efeitos adversos , Correção Endovascular de Aneurisma/instrumentação , Correção Endovascular de Aneurisma/mortalidade , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/cirurgia , Complicações Pós-Operatórias/etiologia , Desenho de Prótese , Reoperação , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: Previous studies document underuse of next-generation sequencing (NGS). We examined the impact to oncology care for veterans of incorporating NGS ordering into the Veterans Affairs (VA) electronic medical record (EMR) at two New York City VA Medical Centers. METHODS: We identified patients with non-small cell lung cancer and prostate cancer with oncology clinic visits and NGS testing indications between January and December 2021. Patients were divided into external ordering (EO) with visits before we implemented an EMR ordering system for NGS in July 2021, and internal ordering (IO) with visits after this date. The primary outcome was proportion of NGS testing performed in EO versus IO groups. Secondary outcomes were time between metastatic disease diagnosis to receipt of test by vendor, time of metastatic diagnosis to result, and proportion of testing by race. RESULTS: A total of 168 patients were identified, 116 EO and 52 IO patients. Between IO and EO periods, testing significantly increased from 52% to 87% (P ≤ .01); it was conducted more quickly, with time from metastatic diagnosis to sample receipt by the NGS vendor improving to median 37 days from 299 days (P = .03); and the time from documented metastatic disease to a test result improved to median 56 days from 309 days (P = .03). The proportion of tissue received by the vendor was not significantly different between the two groups. There were no significant differences in testing according to self-reported race. CONCLUSION: Integration of NGS ordering in the EMR led to increased proportion and speed of testing for a vulnerable patient population served by the country's largest health system.
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Registros Eletrônicos de Saúde , Sequenciamento de Nucleotídeos em Larga Escala , United States Department of Veterans Affairs , Humanos , Masculino , Estados Unidos , Idoso , Pessoa de Meia-Idade , Feminino , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Neoplasias da Próstata/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapiaRESUMO
Objective: The aim of this study was to evaluate the influence of target vessel anatomy and post-stenting geometry on the outcome of fenestrated endovascular aortic repair (f-EVAR). Methods: A retrospective review of data from a single center was conducted, including all consecutive fenestrated endovascular aortic repairs (f-EVARs) performed between September 2018 and December 2023 for thoraco-abdominal aortic aneurysms (TAAAs) and complex abdominal aortic aneurysms (cAAAs). The analysis focused on the correlation of target vessel instability to target vessel anatomy and geometry after stenting. The primary endpoint was the cumulative incidence of target vessel instability. Secondary endpoints were the 30-day and follow-up re-interventions. Results: A total of 136 patients underwent f-EVAR with 481 stented target vessels. A total of ten target vessel instabilities occurred including three in visceral and seven instabilities in renal vessels. The cumulative incidence of target vessel instability with death as the competing risk was 1.4%, 1.8% and 3.4% at 1, 2 and 3 years, respectively. In renal target vessels (260/481), a diameter ≤ 4 mm (OR 1.21, 95% CI 1.035-1.274, p = 0.009) and an aortic protrusion ≥ 5.75 mm (OR 8.21, 95% CI 3.150-12-23, p = 0.027) was associated with an increased target vessel instability. In visceral target vessels (221/481), instability was significantly associated with a preoperative tortuosity index ≥ 1.25 (HR 15.19, CI 95% 2.50-17.47, p = 0.045) and an oversizing ratio of ≥1.25 (HR 7.739, CI % 4.756-12.878, p = 0.049). Conclusions: f-EVAR showed favorable mid-term results concerning target vessel instability in the current cohort. A diameter of ≤4 mm and an aortic protrusion of ≥5.75 mm in the renal target vessels as well as a preoperative tortuosity index and an oversizing of the bridging stent of ≥1.25 in the visceral target vessels should be avoided.
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OBJECTIVE: This study aimed to evaluate the impact of target vessel anatomy and bridging stent geometry on target vessel instability in branched endovascular aortic repair (B-EVAR). METHODS: This retrospective, single centre cohort study included all consecutive B-EVARs performed between September 2018 and December 2022 for thoraco-abdominal aortic aneurysm (TAAA) or complex abdominal aortic aneurysm (CAAA). The primary endpoints were target vessel instability and related re-interventions at 12 months. Secondary endpoints were 30 day results, including target vessel instability and re-interventions. Target vessel instability analysis consisted of assessment of target vessel anatomy, including diameter, aortic trunk to branch angle, and tortuosity. Post-operative parameters included change of clock position/horizontal misalignment, bridging length (gap), sealing length, tortuosity, post-stenting angle, and oversizing ratio. RESULTS: A total of 69 patients (TAAA: n = 56, 81%; CAAA: n = 13, 19%) and 271 (133 visceral and 138 renal) target vessels were included. The cumulative incidence of target vessel instability was 4.8%, 6.4%, and 7.9% at one, two, and three years, respectively. In the renal target vessel group, vessel diameter ≤ 4 mm (hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.116 - 2.54; p = .022) and a bridging length ≥ 25 mm (HR 1.320, 95% CI 1.066 - 1.636; p = .011) were associated with increased target vessel instability. In visceral vessels, a change in clock position/horizontal misalignment ≥ 70 minutes (HR 1.072, 95% CI 1.026 - 1.121; p = .002) showed a significant association with target vessel instability. CONCLUSION: Target vessel diameter, bridging length (gap), and horizontal misalignment seemed to be associated with adverse target vessel outcomes. This may be solved with more customised endograft solutions to reduce the negative impact of the latter parameter.
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Contaminant exposure can harm wildlife. However, measuring contaminant exposure in wildlife can be challenging due to accessibility of species and/or sampling tissue matrices needed to answer research questions regarding exposure. For example, in bats and other taxa that roost, it may be best to collect pooled feces from colonies for minimal disturbance to species of conservation concern, but fecal contaminant concentrations do not provide contaminant bioaccumulation estimates. Thus, there is a need for quantifying relationships between sample matrices for measuring contaminant exposure to answer research questions pertaining to wildlife health and addressing conservation needs. Our goal was to determine relationships between fecal and fur total mercury (THg). To do so, we collected paired feces and fur from Mexican free-tailed bats (Tadarida brasiliensis) in summer 2023 in western Oklahoma at a maternity roost with no known Hg point source. We analyzed THg in each sample matrix for each individual (n = 48). We found no relationship between individual fecal and fur THg. However, when averaged, fur THg was 6.11 times greater than fecal THg. This factor can be used as a screening-level risk assessment of under-roost feces, which could then be followed by direct assessments of fur THg concentrations and health impacts. We encourage the use of this conversion factor across other insectivorous bat species and sites for estimating initial risks of contaminant exposure with minimal disturbance to species of conservation concern, when timely research for conservation actions are needed, and when a contaminant point source is not yet known.
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OBJECTIVE: Fenestrated endovascular aneurysm repair (FEVAR) has become one of the standard treatment options for complex abdominal aortic aneurysms (cAAAs) and thoraco-abdominal aortic aneurysms (TAAAs). Despite technological advances in the main endograft design, the lack of dedicated bridging stent-grafts (BSGs) is still the Achilles heel of the procedure. The aim of this study was to evaluate the mid-term outcomes of the BeGraft stent-graft as a dedicated bridging stent for FEVAR and to review the current evidence in literature. METHODS: Retrospective single center study, including all consecutive FEVARs performed between September 2018 and December 2022 for the treatment of cAAAs and TAAAs with implantation of at least one BeGraft peripheral as the main BSG in one of the target vessels (TVs). Primary endpoints were technical success and TV instability of TV bridged with a BeGraft stent, as well as 30-day mortality and re-intervention rates. Secondary endpoints were follow-up TV instability, re-interventions, and mortality. RESULTS: A total of 113 patients (93 male, mean age 71.1±9.7) and 440 TV (14 scallops and 426 fenestrations) were included. Of the 440 TV, 406 received primary stenting. Be Grafts were used in 88.9% of these (n=361; celiac trunk [CT]=67, superior mesenteric artery [SMA]=98, right renal artery [RRA]=97, and left renal artery [LRA]=99). The technical success rate was 99.4% (359/361). The 30-day TV instability rate was 0.27% (1/361) with one early renal artery occlusion. During a median follow-up of 20 months (6-32), TV instability rate was 0.8% (3/361). Freedom from TV instability was 99.3%, 98.8%, and 98.8% at 1, 2, and 3 years, respectively. CONCLUSION: Early-term and mid-term results regarding TV instability are satisfactory and support the use of BeGraft as BSG in FEVAR for cAAAs and TAAAs. CLINICAL IMPACT: The findings of the current study show that the use of the BeGraft stent graft as bridging stent in FEVAR is associated with a high technical success and low early and mid-term instability rate and support the standard use as a bridging stent in fenestrated aneurysm repair.
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Bacterial pathogens remain poorly characterized in bats, especially in North America. We describe novel (and in some cases panmictic) hemoplasmas (12.9% positivity) and bartonellae (16.7% positivity) across three colonies of Mexican free-tailed bats (Tadarida brasiliensis), a partially migratory species that can seasonally travel hundreds of kilometers. Molecular analyses identified three novel Candidatus hemoplasma species most similar to another novel Candidatus species in Neotropical molossid bats. We also detected novel hemoplasmas in sympatric cave myotis (Myotis velifer) and pallid bats (Antrozous pallidus), with sequences in the latter 96.5% related to C. Mycoplasma haemohominis. We identified eight Bartonella genotypes, including those in cave myotis, with 96.7% similarity to C. Bartonella mayotimonensis. We also detected Bartonella rochalimae in migratory Tadarida brasiliensis, representing the first report of this human pathogen in bats. The seasonality and diversity of these bacteria observed here suggest that additional longitudinal, genomic, and immunological studies in bats are warranted.
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Numerous factors influence the timing of spring migration in birds, yet the relative importance of intrinsic and extrinsic variables on migration initiation remains unclear. To test for interactions among weather, migration distance, parasitism, and physiology in determining spring departure date, we used the Dark-eyed Junco (Junco hyemalis) as a model migratory species known to harbor diverse and common haemosporidian parasites. Prior to spring migration departure from their wintering grounds in Indiana, USA, we quantified the intrinsic variables of fat, body condition (i.e., mass ~ tarsus residuals), physiological stress (i.e., ratio of heterophils to lymphocytes), cellular immunity (i.e., leukocyte composition and total count), migration distance (i.e., distance to the breeding grounds) using stable isotopes of hydrogen from feathers, and haemosporidian parasite intensity. We then attached nanotags to determine the timing of spring migration departure date using the Motus Wildlife Tracking System. We used additive Cox proportional hazard mixed models to test how risk of spring migratory departure was predicted by the combined intrinsic measures, along with meteorological predictors on the evening of departure (i.e., average wind speed and direction, relative humidity, and temperature). Model comparisons found that the best predictor of spring departure date was average nightly wind direction and a principal component combining relative humidity and temperature. Juncos were more likely to depart for spring migration on nights with largely southwestern winds and on warmer and drier evenings (relative to cooler and more humid evenings). Our results indicate that weather conditions at take-off are more critical to departure decisions than the measured physiological and parasitism variables.
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Pathogen evolution is one of the least predictable components of disease emergence, particularly in nature. Here, building on principles established by the geographic mosaic theory of coevolution, we develop a quantitative, spatially explicit framework for mapping the evolutionary risk of viral emergence. Driven by interest in diseases like Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and Coronavirus disease 2019 (COVID-19), we examine the global biogeography of bat-origin betacoronaviruses, and find that coevolutionary principles suggest geographies of risk that are distinct from the hotspots and coldspots of host richness. Further, our framework helps explain patterns like a unique pool of merbecoviruses in the Neotropics, a recently discovered lineage of divergent nobecoviruses in Madagascar, and-most importantly-hotspots of diversification in southeast Asia, sub-Saharan Africa, and the Middle East that correspond to the site of previous zoonotic emergence events. Our framework may help identify hotspots of future risk that have also been previously overlooked, like West Africa and the Indian subcontinent, and may more broadly help researchers understand how host ecology shapes the evolution and diversity of pandemic threats.
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OBJECTIVE: To analyze the outcomes of urgent/emergent endovascular aortic repair of patients with free/contained ruptured thoracoabdominal aortic aneurysms (rTAAA). BACKGROUND: Endovascular repair of rTAAA has been scarcely described in emergent setting. METHODS: An international multicenter retrospective observational study (ClinicalTrials.govID:NCT05956873) from January-2015 to January-2023 in 6 European and 1 United States Vascular Surgery Centers. Primary end-points were technical success, 30-day and/or in-hospital mortality and follow-up survival. RESULTS: A total of 100 rTAAA patients were included (75 male; mean age 73 y). All patients (86 contained and 14 free ruptures) were symptomatic and treated within 24-hours from diagnosis: multi-branched off-the-shelf devices (Zenith t-branch,Cook Medical Inc.Bjaeverskov,Denmark) in 88 patients, physician-modified endografts in 8, patient-specific device or parallel grafts in two patients each. Primary technical success was achieved in 89 patients and 30-day and/or in-hospital mortality was 24%. Major adverse events (MAEs) occurred in 34% of patients (permanent dialysis and paraplegia in 4 and 8 patients, respectively). No statistical differences were detected in mortality rates between free and contained ruptured patients (43%vs.21%; P =0.075). Multivariate analysis revealed contained rupture favoring technical success (Odd-Ratio10.1;95%Confidence-Interval:3.0-33.6; P =<0.001). MAEs (OR9.4;95%C-I:2.8-30.5; P =<0.001) and pulmonary complications (OR11.3;95%CI:3.0-41.5; P =<0.001) were independent risk factors for 30-day and/or in-hospital mortality. Median follow-up time was 13 months (interquartile range 5-24); 1-year survival rate was 65%. Aneurysm diameter>80 mm (Hazard-Ratio:2.0;95%CI:1.0-30.5; P =0.037), technical failure (HR:2.6;95%CI:1.1-6.5; P =0.045) and pulmonary complications (HR:3.0;95%CI:1.2-7.9; P =0.021) were independent risk factors for follow-up mortality. CONCLUSION: Endovascular repair of rTAAA shows high technical success; the presence of free rupture alone appear not to correlate with early mortality. Effective prevention/management of post-operative complications is crucial for survival.
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There is an urgent need for new antibiotics given the rise of antibiotic resistance, and succinyl-diaminopimelate desuccinylase (DapE, E.C. 3.5.1.18) has emerged as a promising bacterial enzyme target. DapE from Haemophilus influenzae (HiDapE) has been studied and inhibitors identified, but it is essential to explore DapE from different species to assess selective versus broad-spectrum therapeutics. We have determined the structure of DapE from the ESKAPE pathogen Acinetobacter baumannii (AbDapE) and studied inhibition by known inhibitors of HiDapE. AbDapE is inhibited by captopril and sulfate comparable to HiDapE, but AbDapE was not significantly inhibited by a known indoline sulfonamide HiDapE inhibitor. Captopril and sulfate both stabilize HiDapE by increasing the thermal melting temperature (Tm) in thermal shift assays. By contrast, sulfate decreases the stability of the AbDapE enzyme, whereas captopril increases the stability. Further, we report two crystal structures of selenomethionine-substituted AbDapE in the closed conformation, one with AbDapE in complex with succinate derived from enzymatic hydrolysis of N6-methyl-l,l-SDAP substrate and acetate (PDB code 7T1Q, 2.25 Å resolution), and a crystal structure of AbDapE with bound succinate along with l-(S)-lactate, a product of degradation of citric acid from the crystallization buffer during X-ray irradiation (PDB code 8F8O, 2.10 Å resolution).