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Personalized cancer immunotherapies such as therapeutic vaccines and adoptive transfer of T cell receptor (TCR)-transgenic T cells rely on the presentation of tumor-specific peptides by human leukocyte antigen (HLA) class I molecules to cytotoxic T cells. Such neoepitopes can for example arise from somatic mutations and their identification is crucial for the rational design of new therapeutic interventions. Liquid chromatography mass spectrometry (LC-MS)-based immunopeptidomics is the only method to directly prove actual peptide presentation and we have developed a parameter optimization workflow to tune targeted assays for maximum detection sensitivity on a per peptide basis, termed optiPRM. Optimization of collision energy using optiPRM allows for improved detection of low abundant peptides that are very hard to detect using standard parameters. Applying this to immunopeptidomics, we detected a neoepitope in a patient-derived xenograft (PDX) from as little as 2.5×106 cells input. Application of the workflow on small patient tumor samples allowed for the detection of five mutation-derived neoepitopes in three patients. One neoepitope was confirmed to be recognized by patient T cells. In conclusion, optiPRM, a targeted MS workflow reaching ultra-high sensitivity by per peptide parameter optimization, which makes the identification of actionable neoepitopes possible from sample sizes usually available in the clinic.
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Various lines of investigation support a signaling interphase shared by receptor tyrosine kinases and the DNA damage response. However, the underlying network nodes and their contribution to the maintenance of DNA integrity remain unknown. We explored MET-related metabolic pathways in which interruption compromises proper resolution of DNA damage. Discovery metabolomics combined with transcriptomics identified changes in pathways relevant to DNA repair following MET inhibition (METi). METi by tepotinib was associated with the formation of γH2AX foci and with significant alterations in major metabolic circuits such as glycolysis, gluconeogenesis, and purine, pyrimidine, amino acid, and lipid metabolism. 5'-Phosphoribosyl-N-formylglycinamide, a de novo purine synthesis pathway metabolite, was consistently decreased in in vitro and in vivo MET-dependent models, and METi-related depletion of dNTPs was observed. METi instigated the downregulation of critical purine synthesis enzymes including phosphoribosylglycinamide formyltransferase, which catalyzes 5'-phosphoribosyl-N-formylglycinamide synthesis. Genes encoding these enzymes are regulated through E2F1, whose levels decrease upon METi in MET-driven cells and xenografts. Transient E2F1 overexpression prevented dNTP depletion and the concomitant METi-associated DNA damage in MET-driven cells. We conclude that DNA damage following METi results from dNTP reduction via downregulation of E2F1 and a consequent decline of de novo purine synthesis. SIGNIFICANCE: Maintenance of genome stability prevents disease and affiliates with growth factor receptor tyrosine kinases. We identified de novo purine synthesis as a pathway in which key enzymatic players are regulated through MET receptor and whose depletion via MET targeting explains MET inhibition-associated formation of DNA double-strand breaks. The mechanistic importance of MET inhibition-dependent E2F1 downregulation for interference with DNA integrity has translational implications for MET-targeting-based treatment of malignancies.
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Daño del ADN , Factor de Transcripción E2F1 , Proteínas Proto-Oncogénicas c-met , Purinas , Daño del ADN/efectos de los fármacos , Purinas/biosíntesis , Purinas/metabolismo , Animales , Ratones , Humanos , Factor de Transcripción E2F1/metabolismo , Factor de Transcripción E2F1/genética , Proteínas Proto-Oncogénicas c-met/metabolismo , Proteínas Proto-Oncogénicas c-met/genética , Reparación del ADN/efectos de los fármacos , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Transducción de Señal/efectos de los fármacosRESUMEN
Many everyday decisions, including those concerning our health, finances and the environment, involve choosing between a smaller but imminent reward (e.g., 20 now) and a later but larger reward (e.g., 40 in a month). The extent to which an individual prefers smaller imminent rewards over larger delayed rewards can be measured using delay discounting tasks. Acute stress induces a cascade of biological and psychological responses with potential consequences for how individuals think about the future, process rewards, and make decisions, all of which can impact delay discounting. Several studies have shown that individuals focus more on imminent rewards under stress. These findings have been used to explain why individuals make detrimental choices under acute stress. Yet, the evidence linking acute stress to delay discounting is equivocal. To address this uncertainty, we conducted a meta-analysis of 11 studies (14 effects) to systematically quantify the effects of acute stress on monetary delay discounting. Overall, we find no effect of acute stress on delay discounting, compared to control conditions (SMD = -0.18, 95% CI [-0.57, 0.20], p = 0.32). We also find that neither the gender/sex of the participants, the type of stressor (e.g., physical vs. psychosocial) nor whether monetary decisions were hypothetical or incentivized (i.e. monetary decisions were actually paid out) moderated the impact of acute stress on monetary delay discounting. We argue that establishing the effects of acute stress on the separate processes involved in delay discounting, such as reward valuation and prospection, will help to resolve the inconsistencies in the field.
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BACKGROUND: Current management of mesenteric ischemia is primarily endovascular stent treatment. Typical CMI symptoms are postprandial abdominal pain, food fear, weight loss, and diarrhea. Revascularization is often necessary, as mesenteric ischemia may progress to bowel necrosis and death if left untreated. This study aims to compare the outcome using bare metal stent (BMS) or covered stent (CS) in the endovascular treatment of chronic and acute on chronic mesenteric ischemia. METHODS: This is an investigator-driven, prospective, randomized, single-blinded, and single-center, national cohort study at the Copenhagen University Hospital, Denmark. A total of 98 patients with chronic mesenteric ischemia (CMI) and acute-on-chronic mesenteric ischemia (AoCMI) will be randomized to treatment with either BeSmooth BMS (Bentley Innomed GmbH) or BeGraft CS (Bentley Innomed GmbH). Randomization occurs intraoperatively after lesion crossing. DISCUSSION: There is currently no published data from prospective controlled trials regarding the preferred type of stent used for the treatment of chronic and acute-on-chronic mesenteric ischemia. This trial will evaluate the short- and long-term outcome of BMS versus CS when treating CMI and AoCMI, as well as the benefit of a more intense postoperative surveillance program. TRIAL REGISTRATION: ClinicalTrials.gov NCT05244629. Registered on February 8, 2022.
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Isquemia Mesentérica , Stents , Humanos , Isquemia Mesentérica/terapia , Isquemia Mesentérica/cirugía , Estudios Prospectivos , Método Simple Ciego , Enfermedad Crónica , Dinamarca , Resultado del Tratamiento , Procedimientos Endovasculares/instrumentación , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Diseño de PrótesisRESUMEN
Large mediastinal lipomas are rare. Complete surgical resection can be difficult due to the intricate anatomy in the mediastinum. We report the case of a 75-year-old man with worsened retrosternal pressure, decline in performance and syncope episodes. Computed tomography revealed a large retrocardiac low-attenuated mediastinal lesion measuring 10 × 8 cm, compressing the left atrium and pulmonary veins bilaterally. Surgical exploration was achieved through a right anterolateral thoracotomy with a successful en bloc resection without any intraoperative complications. The total operation time was 185 min with a total blood loss of <250 ml. Stand-by extracorporeal life support was present throughout the procedure, but its use was not required. The postoperative course was uneventful. The pathological examination revealed a mature mediastinal lipoma without any evidence of malignancy. In the 12-month control the patient was completely free of symptoms and in a good general condition.
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BACKGROUND: The world is moving towards the third target of the Joint United Nations Programme on HIV/AIDS to ensure most people receiving antiretroviral therapy (ART) are virologically suppressed. Little is known about viral suppression at an undetectable level and the risk of viral rebound phenomenon in sub-Saharan Africa which covers 67% of the global HIV burden.This study aimed to investigate the proportion of viral suppression at an undetectable level and the risk of viral rebound among people living with HIV receiving ART in northern Tanzania. METHODOLOGY: A hospital based-retrospective study recruited people living with HIV who were on ART for at least two years at Kibong'oto Infectious Disease Hospital and Mawenzi Regional Referral Hospital in Kilimanjaro Region, Tanzania. Participants' two-year plasma HIV were captured at months 6, 12, and 24 of ART. Undetectable viral load was defined by plasma HIV of viral load (VL) less than 20copies/ml and viral rebound (VR) was considered to anyone having VL of more than 50 copies/ml after having history of undetectable level of the VL less than 20copies/ml. A multivariable log-binomial generalized linear model was used to determine factors for undetectable VL and viral VR. RESULTS: Among 416 PLHIV recruited, 226 (54.3%) were female. The mean (standard deviation) age was 43.7 (13.3) years. The overall proportion of undetectable VL was 68% (95% CI: 63.3-72.3) and 40.0% had viral rebound (95% CI: 34.7-45.6). Participants who had at least 3 clinic visits were 1.3 times more likely to have undetectable VL compared to those who had 1 to 2 clinic visits in a year (p = 0.029). Similarly, participants with many clinical visits ( > = 3 visits) per year were less likely to have VR compared to those with fewer visits ( = 2 visits) [adjusted relative risk (aRR) = 0.64; 95% CI: 0.44-0.93]. CONCLUSION: Participants who had fewer clinic visits per year(ART refills) were less likely to achieve viral suppression and more likely to experience viral rebound. Enhanced health education and close follow-up of PLHIV on antiretroviral therapy are crucial to reinforce adherence and maintain an undetectable viral load.
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Síndrome de Inmunodeficiencia Adquirida , Fármacos Anti-VIH , Infecciones por VIH , Humanos , Femenino , Adulto , Masculino , Estudios Retrospectivos , Terapia Antirretroviral Altamente Activa , Tanzanía/epidemiología , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Carga Viral , Fármacos Anti-VIH/uso terapéuticoRESUMEN
Binary coalescences are known sources of gravitational waves (GWs) and they encompass combinations of black holes (BHs) and neutron stars (NSs). Here we show that when BHs are embedded in magnetic fields (B's) larger than approximately 10^{10} G, charged particles colliding around their event horizons can easily have center-of-mass energies in the range of ultrahigh energies (â³10^{18} eV) and become more likely to escape. Such B-embedding and high-energy particles can take place in BH-NS binaries, or even in BH-BH binaries with one of the BHs being charged (with charge-to-mass ratios as small as 10^{-5}, which do not change GW waveforms) and having a residual accretion disk. Ultrahigh center-of-mass energies for particle collisions arise for basically any rotation parameter of the BH when Bâ³10^{10} G, meaning that it should be a common aspect in binaries, especially in BH-NS ones given the natural presence of a B onto the BH and charged particles due to the magnetosphere of the NS. We estimate that the number of ultrahigh center-of-mass collisions ranges from a few up to millions before the merger of binary compact systems. Thus, binary coalescences may also be efficient sources of ultrahigh energy cosmic rays (UHECRs) and constraints to NS/BH parameters would be possible if UHECRs are detected along with GWs.
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BACKGROUND: Foreign bodies within the pleura and pancreas are infrequent, and the approaches to their treatment still a subject of debate. There is limited knowledge particularly regarding glass foreign bodies. METHODS: We present a case involving large glass splinters in the pleura and pancreas, with an unknown entry point. In addition, a systematic review was conducted to explore entry hypotheses and management options. RESULTS: In addition to our case, our review uncovered eight incidents of intrapleural glass, and another eight cases of glass in other intrathoracic areas. The fragments entered the body through impalement (81%), migrated through the diaphragm after impalement (6%), or caused transesophageal perforation (19%) following ingestion. Eight instances of glass inside the abdominal cavity were documented, with seven resulting from impalement injuries and one from transintestinal migration. There were no recorded instances of glass being discovered within the pancreas. Among the 41 nonglass intrapancreatic foreign bodies found, sewing needles (34%) and fish bones (46%) were the most common; following ingestion, they had migrated through either a transgastric or transduodenal perforation. In all these cases, how the foreign bodies were introduced was often poorly recalled by the patient. Many nonglass foreign bodies tend to become encapsulated by fibrous tissue, rendering them inert, though this is less common with glass. Glass has been reported to migrate through various tissues and cavities, sometimes with a significant delay spanning even decades. There are cases of intrapleural migration of glass causing hemothorax, pneumothorax, and heart and major blood vessels injury. For intrapleural glass fragment management, thoracoscopy proved to be effective in 5 reported cases, in addition to our patient. Most intrapancreatic nonglass foreign bodies tend to trigger pancreatitis and abscess formation, necessitating management ranging from laparoscopic procedures to subtotal pancreatectomy. There have been only four documented cases of intrapancreatic needles that remained asymptomatic with conservative management. There is no direct guidance from the existing literature regarding management of intrapancreatic glass foreign bodies. Consequently, our patient is under observation with regular follow-ups and has remained asymptomatic for the past 2 years. CONCLUSIONS: Glass foreign bodies in the pleura are rare, and our report of an intrapancreatic glass fragment is the first of its kind. Impalement is the most likely method of introduction. As glass has significant migration and an ensuing complication potential, preventive removal of intrapleural loose glass should be considered. However, intrapancreatic glass fragment management remains uncertain.
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Cuerpos Extraños , Vidrio , Páncreas , Pleura , Humanos , Cuerpos Extraños/cirugía , Pleura/lesiones , Páncreas/lesiones , Migración de Cuerpo Extraño/cirugía , Migración de Cuerpo Extraño/etiología , Masculino , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: During the COVID-19 pandemic, with many nurses being infected, understanding compliance with standard precautions (SP) among nurses in Kazakhstan is crucial for improving infection prevention and control and preparedness for future emergencies. The study aimed to assess Kazakh nurses' SP compliance amid the COVID-19 pandemic and examine the factors associated with their compliance. METHODS: Quantitative, cross-sectional design. This research surveyed 241 clinical nurses in Astana, Kazakhstan using a standardized tool from December 2021 to April 2022. RESULTS: This study found 76.0% SP compliance among the nurses. The highest compliance was observed in the dimension "Decontamination of spills and used articles" (86.0% compliance rate), followed by "Use of protective devices" (83.5% compliance rate), "Prevention of cross-infection from person to person" (72.7% compliance rate), "Disposal of sharps" (65.4% compliance rate), and "Disposal of waste" (56.0% compliance rate). Nurses' age and educational qualification influences the nurses' SP compliance. DISCUSSION: While the nurses' compliance rate in this study was moderate, specific areas warrant more attention, such as their compliance with proper waste and sharps disposal. CONCLUSIONS: This study highlighted the experiences of nurses in Kazakhstan on their compliance with SP during the pandemic.
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COVID-19 , Adhesión a Directriz , Control de Infecciones , Humanos , Kazajstán , Estudios Transversales , COVID-19/prevención & control , COVID-19/epidemiología , Adhesión a Directriz/estadística & datos numéricos , Adulto , Femenino , Masculino , Control de Infecciones/métodos , Control de Infecciones/normas , Enfermeras y Enfermeros/psicología , SARS-CoV-2 , Encuestas y Cuestionarios , Persona de Mediana Edad , Precauciones Universales , Adulto JovenRESUMEN
BACKGROUND: There is a scarcity of scientific data regarding the correlation between alignment techniques during total knee arthroplasty (TKA) and blood loss as well as transfusion rates. This study's hypothesis posited that intramedullary-aligned (IM) TKA exhibits higher blood loss and transfusion rates when contrasted with extramedullary-aligned (EM) TKA. METHODS: We conducted a retrospective examination of 883 patients who underwent total knee arthroplasty (TKA) in 2021 at a solitary orthopedic center in Germany. These patients were divided into two groups based on their tibial alignment technique: extramedullary alignment and intramedullary tibial alignment. RESULTS: In the intramedullary tibial alignment (IM) group, we observed a blood loss of 0.91 L, while in the extramedullary tibial alignment (EM) group, the blood loss was 0.89 L. These values did not demonstrate a significant difference (p = 0.69). Transfusion rates were 0.99% in the IM group and 0.21% in the EM group, and there was no significant distinction between them (Chi-squared test: p > 0.05). CONCLUSION: We observed no statistically significant variance in blood loss between the IM and EM groups. Likewise, there was no substantial disparity in transfusion rates between these groups. It can be concluded that the selection of a knee arthroplasty system incorporating either intramedullary tibial alignment or extramedullary alignment does not significantly impact blood loss.
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Artroplastia de Reemplazo de Rodilla , Pérdida de Sangre Quirúrgica , Transfusión Sanguínea , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Estudios Retrospectivos , Femenino , Masculino , Anciano , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Persona de Mediana Edad , Transfusión Sanguínea/estadística & datos numéricos , Anciano de 80 o más Años , Tibia/cirugíaRESUMEN
Cardiovascular disease is the leading cause of death, with atherosclerosis the major underlying cause. While often asymptomatic for decades, atherosclerotic plaque destabilization and rupture can arise suddenly and cause acute arterial occlusion or peripheral embolization resulting in myocardial infarction, stroke and lower limb ischaemia. As extracellular matrix (ECM) remodelling is associated with plaque instability, we hypothesized that the ECM composition would differ between plaques. We analyzed atherosclerotic plaques obtained from 21 patients who underwent carotid surgery following recent symptomatic carotid artery stenosis. Plaques were solubilized using a new efficient, single-step approach. Solubilized proteins were digested to peptides, and analyzed by liquid chromatography-mass spectrometry using data-independent acquisition. Identification and quantification of 4498 plaque proteins was achieved, including 354 ECM proteins, with unprecedented coverage and high reproducibility. Multidimensional scaling analysis and hierarchical clustering indicate two distinct clusters, which correlate with macroscopic plaque morphology (soft/unstable versus hard/stable), ultrasound classification (echolucent versus echogenic) and the presence of hemorrhage/ulceration. We identified 714 proteins with differential abundances between these groups. Soft/unstable plaques were enriched in proteins involved in inflammation, ECM remodelling, and protein degradation (e.g. matrix metalloproteinases, cathepsins). In contrast, hard/stable plaques contained higher levels of ECM structural proteins (e.g. collagens, versican, nidogens, biglycan, lumican, proteoglycan 4, mineralization proteins). These data indicate that a single-step proteomics method can provide unique mechanistic insights into ECM remodelling and inflammatory mechanisms within plaques that correlate with clinical parameters, and help rationalize plaque destabilization. These data also provide an approach towards identifying biomarkers for individualized risk profiling of atherosclerosis.
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OBJECTIVE: To evaluate the risk of miscarriage following SARS-CoV-2 vaccination, while accounting for the competing risk of induced abortion. DESIGN: Population-based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: Women aged 15-50 years with a confirmed pregnancy at ≤19 completed weeks' gestation. METHODS: Exposure to first SARS-CoV-2 vaccination, handled in a time-varying manner, was defined as (i) unvaccinated, (ii) remotely vaccinated >28 days before the estimated conception date or (iii) recently vaccinated ≤28 days before conception and up to 120 days after conception. MAIN OUTCOME MEASURES: The outcome was miscarriage, occurring between the estimated date of conception and up to 19 completed weeks of pregnancy. Fine-Grey hazard models, accounting for the competing risk of induced abortion, generated hazard ratios (aHR), adjusted for socio-demographic factors, comorbidities, and biweekly periods. RESULTS: Included were 246 259 pregnant women, of whom 34% received a first SARS-CoV-2 vaccination. Miscarriage occurred at a rate of 3.6 per 10 000 person-days among remotely vaccinated women and 3.2 per 10 000 person-days among those recently vaccinated, in contrast to a rate of 1.9 per 10 000 person-days among unvaccinated women, with corresponding aHR of 0.98 (95% confidence interval [CI] 0.91-1.07) and 1.00 (95% CI 0.93-1.08). CONCLUSIONS: SARS-CoV-2 vaccination was not associated with miscarriage while accounting for the competing risk of induced abortion. This study reiterates the importance of including pregnant women in new vaccine clinical trials and registries, and the rapid dissemination of vaccine safety data.
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Aborto Espontáneo , Vacunas contra la COVID-19 , COVID-19 , Femenino , Humanos , Embarazo , Aborto Espontáneo/epidemiología , Aborto Espontáneo/etiología , Estudios de Cohortes , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Ontario/epidemiología , SARS-CoV-2 , Vacunación/efectos adversosRESUMEN
OBJECTIVE: Endovascular aortic repair (EVAR) is being used increasingly for the treatment of infrarenal abdominal aortic aneurysms. Improvement in educational strategies is required to teach future vascular surgeons EVAR skills, but a comprehensive, pre-defined e-learning and simulation curriculum remains to be developed and tested. EndoVascular Aortic Repair Assessment of Technical Expertise (EVARATE), an assessment tool for simulation based education (SBE) in EVAR, has previously been designed to assess EVAR skills, and a pass limit defining mastery level has been set. However, EVARATE was developed for anonymous video ratings in a research setting, and its feasibility for real time ratings in a standardised SBE programme in EVAR is unproven. This study aimed to test the effect of a newly developed simulation based modular course in EVAR. In addition, the applicability of EVARATE for real time performance assessments was investigated. METHODS: The European Society of Vascular Surgery (ESVS) and Copenhagen Certification Programme in EVAR (ENHANCE-EVAR) was tested in a prospective cohort study. ENHANCE-EVAR is a modular SBE programme in EVAR consisting of e-learning and hands-on SBE. Participants were rated with the EVARATE tool by experienced EVAR surgeons. RESULTS: Twenty-four physicians completed the study. The mean improvement in EVARATE score during the course was +11.8 (95% confidence interval 9.8 - 13.7) points (p < .001). Twenty-two participants (92%) passed with a mean number of 2.8 ± 0.7 test attempts to reach the pass limit. Cronbach's alpha coefficient was 0.91, corresponding to excellent reliability of the EVARATE scale. Differences between instructors' EVARATE ratings were insignificant (p = .16), with a maximum variation between instructors of ± 1.3 points. CONCLUSION: ENHANCE-EVAR, a comprehensive certifying EVAR course, was proven to be effective. EndoVascular Aortic Repair Assessment of Technical Expertise (EVARATE) is a trustworthy tool for assessing performance within an authentic educational setting, enabling real time feedback.
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Aneurisma de la Aorta Abdominal , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Humanos , Reparación Endovascular de Aneurismas , Estudios Prospectivos , Reproducibilidad de los Resultados , Procedimientos Quirúrgicos Vasculares/educación , Aneurisma de la Aorta Abdominal/cirugía , Certificación , Procedimientos Endovasculares/educación , Implantación de Prótesis Vascular/efectos adversos , Resultado del Tratamiento , Factores de RiesgoRESUMEN
The golden flathead goby Glossogobius aureus is a native species in the Philippines, Australia, Japan, Taiwan, and many other countries in Asia. In the Philippines, it is an important food fish as it is commonly caught in major lakes. In this study, a total of 307 specimens morphologically identified as G. aureus were sampled from nine major lakes in the Philippines and were sequenced for their mitochondrial cytochrome b (cyt b) gene. Two hundred sixty of the 307 cyt b sequences had sequence similarities of ≥ 99% with G. aureus reference sequence in GenBank, while the remaining 47 (all from Lake Lanao) had sequence similarities of only 95% and were thus designated as Glossogobius cf. aureus and treated as a separate population. The sequences were then analyzed to examine the pattern of genetic diversity, relatedness, divergence, and demographic history among native and translocated populations of the species. Twenty-nine haplotypes were recovered, of which four haplotypes were shared among three to seven populations. Only one haplotype each was found in the native population in Lake Buhi and translocated population in Lake Paoay. Low haplotype and low nucleotide diversities were found for the populations in Laguna de Bay, Lanao, Bato, Buhi, Paoay, and Sebu lakes, which indicate founder event for the introduced populations in Lanao, Paoay, and Sebu lakes and recent genetic bottleneck for the native populations in Laguna de Bay, Bato, and Buhi. In contrast, high haplotype but low nucleotide diversities were found for the native populations of Taal, Naujan, and Buluan lakes, signifying a recent bottleneck followed by population expansion. Pairwise FST values showed generally large (FST = 0.168-0.249) to very large (FST = 0.302-1.000) genetic divergence between populations except between Laguna de Bay and Lake Bato, Laguna de Bay and Lake Buhi, and Lake Bato and Lake Buhi populations, which showed nonsignificant genetic differentiation. Lake Buluan and Lake Sebu populations showed moderate genetic differentiation (FST = 0.098). Neutrality tests showed significant negative Tajima's D and Fu's FS values only for the population from Laguna de Bay, which suggests that the population is undergoing expansion. These results are important for establishing scientifically sound strategies for effective conservation and sustainable exploitation of G. aureus in the Philippines.
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Variación Genética , Perciformes , Animales , ADN Mitocondrial/genética , Lagos , Filipinas , Citocromos b/genética , Peces/genética , Perciformes/genética , Haplotipos , Nucleótidos , FilogeniaRESUMEN
Background and Objectives: Opioid overprescribing in patients undergoing breast surgery is a concern, as evidence suggests that minimal or no opioid is needed to manage pain. We sought to describe characteristics of opioid prescribers and determine associations between prescriber's characteristics and high opioid prescribing within 7 days of same-day breast surgery. Methods: Patients ≥18 years of age who underwent same-day breast surgery in Ontario, Canada from 2012 to 2020 were identified and linked to prescriber data. The primary outcome was current high opioid prescribing defined as >75th percentile of the mean oral morphine equivalents (OME; milligrams). Prescriber characteristics including age, sex, specialty, years in practice, practice setting, and history of high (>75th percentile) opioid prescribing in the previous year were captured. Associations between prescriber characteristics and the primary outcome were estimated in modified Poisson regression models. Results: The final cohort contained 56,434 patients, 3469 unique prescribers, and 58,656 prescriptions. Over half (1971/3469; 57%) of prescribers wrote ≥1 prescription that was >75th percentile of mean OME of 180 mg, of which 50% were family practice physicians. Adjusted mean OMEs prescribed varied by specialty with family practice specialties prescribing the highest mean OME (614 ± 38 mg) compared to surgical specialties (general surgery [165 ± 9 mg], plastic surgery [198 ± 10 mg], surgical oncology [154 ± 14 mg]). Whereas 73% of first and 31% of second prescriptions were provided by general surgery physicians, family practice physicians provided 2% of first and 51% of second prescriptions. Prescriber characteristics associated with a higher likelihood of high current opioid prescribing were family practice (risk ratio [RR], 1.56; 95% confidence interval [CI], 1.35-1.79 compared to general surgery), larger community practice setting (RR, 1.34; 95% CI, 1.05-1.71 compared to urban), and a previous high opioid prescribing behavior (RR, 2.28; 95% CI, 2.06-2.52). Conclusions: While most studies examine surgeon opioid prescribing, our data suggest that other specialties contribute to opioid overprescribing in surgical patients and identify characteristics of physicians likely to overprescribe.
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BACKGROUND: Three-dimensional ultrasound (3D-US) and computed tomography (CT) have proven abdominal aortic aneurysm (AAA) volume a more sensitive measure of growth than diameter. This proof-of-concept study aimed to investigate the clinical applicability of two-dimensional ultrasound and 3D-US for AAA diameter and volume growth pattern evaluation. METHODS: AAA patients with at least three follow-ups within a minimum of 24 months were included prospectively and consecutively from the COpenhagen Aneurysms CoHort (COACH). Individual diameter and volume growth rates were categorized as rapid, slow, or no growth (>6.0, 3.8-6.0, and ≤3.7 mm/year for diameter. >17.4, 8.8-17.3, and ≤8.7 mL/year for volume). Similarly, diameter and volume growth patterns were categorized as as linear, exponential, staccato, and indeterminate growth, based from individual regressions. RESULTS: Thirty patients were included, of which 19 (63%) had no diameter growth, 10 (33%) had slow growth, and one (3%) had rapid growth. Regarding volume, 11 (37%) patients had no growth, 12 (40%) had slow growth, and seven (23%) had rapid growth. Growth patterns according to diameter showed that 18 (60%) patients had linear growth, none had staccato or exponential growth. Twelve (40%) were indeterminate. Volume growth patterns found 19 (63%) patients with linear growth, 3 (10%) with staccato, and none with exponential growth. Eight (27%) were indeterminate. CONCLUSIONS: Analysis of AAA volume growth patterns is a practical and safe modality that seems more sensitive at detecting growth patterns than AAA diameter. Volume also detects more AAA growth than diameter.
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Aneurisma de la Aorta Abdominal , Humanos , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
Stereochemical comparability is critical for ensuring manufacturing consistency in therapeutic phosphorothioate oligonucleotides. Currently, analytical methods for this assessment are limited. We hereby report on a novel protocol capable of detecting a stereochemistry change in a single phosphorothioate linkage by employing nuclease P1 digestion of the oligonucleotide with subsequent LCMS analysis of the resulting fragments. The method proves valuable for establishing stereochemical comparability and for ensuring manufacturing consistency of oligonucleotide therapeutics.
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BACKGROUND: Burnout among physicians has widespread negative consequences. Little is known about burnout among European vascular surgeons (VS). A previously published study found that 82% of VS and vascular surgical trainees (VST) in Denmark experience burnout symptoms. The present study aimed to investigate work- and health-related consequences of burnout. STUDY DESIGN: An electronic survey was distributed to all VS/VST in Denmark in January 2020. Validated assessment tools were used to measure burnout, mental health, and psychosocial work environment aspects. RESULTS: Of 104 invited VS/VST, 82% (n = 85) completed the survey. VS accounted for 72% (n = 61) of the respondents, and 40% (n = 33) were female. Statistically significant associations were found between higher levels of burnout and a range of work- and health-related outcomes, including a sense of meaning at work, workplace commitment, conflicts between work and private life, work stress, sick leave, and depressive symptoms. VS/VST using pain medication daily or weekly had significantly higher burnout scores than respondents who rarely or never use pain medication. A significant association between burnout and job satisfaction and retention was found, with respondents indicating an intention to stay within the specialty having significantly lower burnout scores than those who considered leaving within 5 years. Among those who indicated leaving the specialty, 35% (n = 13) attributed this to their current working conditions. CONCLUSIONS: Burnout among VS/VST in Denmark is negatively associated with various work- and health-related outcomes. The work environment seems to play an essential role in these associations, and alterations in workplace organization may remedy this situation.
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Agotamiento Profesional , Estrés Laboral , Cirujanos , Humanos , Femenino , Masculino , Agotamiento Profesional/psicología , Estrés Laboral/psicología , Cirujanos/psicología , Encuestas y Cuestionarios , Dolor , Dinamarca/epidemiología , Satisfacción en el TrabajoRESUMEN
We present the case of a 75-year-old man with a symptomatic penetrating aortic ulcer located in zone 2 on the arch inner curve between the left subclavian artery and left carotid artery treated using a single branch thoracic endovascular aortic repair combined with in situ laser fenestration. The patient underwent a successful procedure with no neurologic impairment and was discharged on the second postoperative day. The postoperative follow-up showed a well-excluded penetrating aortic ulcer.