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Quantum computers hold the promise of solving computational problems that are intractable using conventional methods1. For fault-tolerant operation, quantum computers must correct errors occurring owing to unavoidable decoherence and limited control accuracy2. Here we demonstrate quantum error correction using the surface code, which is known for its exceptionally high tolerance to errors3-6. Using 17 physical qubits in a superconducting circuit, we encode quantum information in a distance-three logical qubit, building on recent distance-two error-detection experiments7-9. In an error-correction cycle taking only 1.1 µs, we demonstrate the preservation of four cardinal states of the logical qubit. Repeatedly executing the cycle, we measure and decode both bit-flip and phase-flip error syndromes using a minimum-weight perfect-matching algorithm in an error-model-free approach and apply corrections in post-processing. We find a low logical error probability of 3% per cycle when rejecting experimental runs in which leakage is detected. The measured characteristics of our device agree well with a numerical model. Our demonstration of repeated, fast and high-performance quantum error-correction cycles, together with recent advances in ion traps10, support our understanding that fault-tolerant quantum computation will be practically realizable.
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Various subspecies of the unicellular parasite Trypanosoma brucei cause sleeping sickness, a neglected tropical disease affecting millions of individuals and domestic animals. Immune evasion mechanisms play a pivotal role in parasite survival within the host and enable the parasite to establish a chronic infection. In particular, the rapid switching of variant surface glycoproteins covering a large proportion of the parasite's surface enables the parasite to avoid clearance by the adaptive immune system of the host. In this article, we present the crystal structure and discover an immune-evasive function of the extracellular region of the T. brucei invariant surface gp75 (ISG75). Structural analysis determined that the ISG75 ectodomain is organized as a globular head domain and a long slender coiled-coil domain. Subsequent ligand screening and binding analysis determined that the head domain of ISG75 confers interaction with the Fc region of all subclasses of human IgG. Importantly, the ISG75-IgG interaction strongly inhibits both activation of the classical complement pathway and Ab-dependent cellular phagocytosis by competing with C1q and host cell FcγR CD32. Our data reveal a novel immune evasion mechanism of T. brucei, with ISG75 able to inactivate the activities of Abs recognizing the parasite surface proteins.
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Trypanosoma brucei brucei , Animales , Humanos , Receptores Fc/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas Portadoras/metabolismo , Inmunoglobulina G/metabolismo , Fagocitosis , Activación de ComplementoRESUMEN
Alginate is a polysaccharide consumed by humans in edible seaweed and different foods where it is applied as a texturizing hydrocolloid or in encapsulations of drugs and probiotics. While gut bacteria are found to utilize and ferment alginate to health beneficial short chain fatty acids, knowledge on details of the molecular reactions is sparse. Alginates are composed of mannuronic acid (M) and its C-5 epimer guluronic acid (G). An alginate related polysaccharide utilization locus (PUL) has been identified in the gut bacterium Bacteroides eggerthii DSM 20697. The PUL encodes two polysaccharide lyases (PLs) from the PL6 (BePL6) and PL17 (BePL17) families as well as a KdgF-like metalloprotein (BeKdgF) known to catalyze ring-opening of 4,5-unsaturated monouronates yielding 4-deoxy-l-erythro-5-hexoseulose uronate (DEH). B. eggerthii DSM 20697 does not grow on alginate, but readily proliferates with a lag phase of a few hours in the presence of an endo-acting alginate lyase A1-I from the marine bacterium Sphingomonas sp. A1. The B. eggerthii lyases are both exo-acting and while BePL6 is strictly G-block specific, BePL17 prefers M-blocks. BeKdgF retained 10-27% activity in the presence of 0.1-1 mM EDTA. X-ray crystallography was used to investigate the three-dimensional structure of BeKdgF, based on which a catalytic mechanism was proposed to involve Asp102, acting as acid/base having pKa of 5.9 as determined by NMR pH titration. BePL6 and BePL17 cooperate in alginate degradation with BeKdgF linearizing produced 4,5-unsaturated monouronates. Their efficiency of alginate degradation was much enhanced by addition of the A1-I alginate lyase.
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Trypanosomes are known to activate the complement system on their surface, but they control the cascade in a manner such that the cascade does not progress into the terminal pathway. It was recently reported that the invariant surface glycoprotein ISG65 from Trypanosoma brucei interacts reversibly with complement C3 and its degradation products, but the molecular mechanism by which ISG65 interferes with complement activation remains unknown. In this study, we show that ISG65 does not interfere directly with the assembly or activity of the two C3 convertases. However, ISG65 acts as a potent inhibitor of C3 deposition through the alternative pathway in human and murine serum. Degradation assays demonstrate that ISG65 stimulates the C3b to iC3b converting activity of complement factor I in the presence of the cofactors factor H or complement receptor 1. A structure-based model suggests that ISG65 promotes a C3b conformation susceptible to degradation or directly bridges factor I and C3b without contact with the cofactor. In addition, ISG65 is observed to form a stable ternary complex with the ligand binding domain of complement receptor 3 and iC3b. Our data suggest that ISG65 supports trypanosome complement evasion by accelerating the conversion of C3b to iC3b through a unique mechanism.
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Trypanosoma brucei brucei , Ratones , Animales , Humanos , Trypanosoma brucei brucei/metabolismo , Complemento C3b/metabolismo , Receptores de Complemento 3b , Activación de Complemento , Factor H de Complemento/metabolismo , Fibrinógeno , Vía Alternativa del Complemento , Convertasas de Complemento C3-C5/metabolismoRESUMEN
Measurement of total cortisol levels in serum samples is currently based on immunoassays or liquid chromatography-mass spectrometry (LC-MS/MS). However, measurement of bioavailable cortisol is laborious, unreliable, and inconvenient for the patient. Therefore, a new versatile assay with the ability to measure both total and bioavailable cortisol from serum represents an important supplement to the current methods. We have generated a cell-based glucocorticoid reporter assay (HEK293F-GRE). The assay was validated for cell line stability, accuracy by dilution, precision, repeatability, reproducibility, and specificity. Additionally, the assay was tested for measuring both total and bioavailable cortisol in serum. The assay showed linearity at five dilution levels with R2 = 0.98 and an accuracy between 0.8 and 1.2. Precision (CV < 20%) was validated down to 3-6 nM dexamethasone, and estimation of the total cortisol concentration was comparable to cortisol immunoassay and LC-MS/MS in most serum samples. Moreover, the assay estimated the bioavailable cortisol fraction in serum samples to a level that agreed with the literature. The HEK293F-GRE assay holds the potential to be a complementary method for estimating cortisol in clinical practice. The ability to quantify bioavailable cortisol directly from serum samples is alluring and provides an opportunity for monitored and personal dose regimens of exogenous glucocorticoids.
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Glucocorticoides , Hidrocortisona , Humanos , Cromatografía Liquida/métodos , Reproducibilidad de los Resultados , Espectrometría de Masas en Tándem/métodosRESUMEN
PURPOSE OF REVIEW: To provide a comprehensive review of hypertension among patients with cancer. Several cancer therapies cause hypertension which has resulted in a growing and vulnerable population of patients with difficult to control hypertension which has significant downstream effects. RECENT FINDINGS: Hypertension affects up to 50% of cancer patients and higher comorbidity when compared to the general population. Many anticancer therapies can cause hypertension through their treatment effect. Antihypertensive treatment is crucial given cardiovascular mortality is a leading cause of death among cancer patients. It is already known that hypertension is poorly controlled in the general population, and there are additional challenges in management among patients with cancer. Patients with cancer suffer from multimorbidity, are on multiple medications creating concern for drug interactions, and often have blood pressure lability, which can worsen clinical inertia among patients and their providers. It is crucial to effectively treat hypertension in cancer patients to mitigate downstream adverse cardiovascular events. SUMMARY: In recent years, there have been significant changes in management guidelines of hypertension and simultaneously as influx of new cancer therapeutics. We provide an update on hypertension treatment among patients with cancer on different chemotherapeutic agents.
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Antihipertensivos , Antineoplásicos , Hipertensión , Neoplasias , Humanos , Hipertensión/inducido químicamente , Hipertensión/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Antihipertensivos/uso terapéutico , Antihipertensivos/efectos adversos , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Manejo de la Enfermedad , Presión Sanguínea/efectos de los fármacosRESUMEN
BACKGROUND AND PURPOSE: Data on clinical features and outcomes of benign recurrent lymphocytic meningitis (BRLM) are limited. METHODS: This was a nationwide population-based cohort study of all adults hospitalized for BRLM associated with herpes simplex virus type 2 (HSV-2) at the departments of infectious diseases in Denmark from 2015 to 2020. Patients with single-episode HSV-2 meningitis were included for comparison. RESULTS: Forty-seven patients with BRLM (mean annual incidence 1.2/1,000,000 adults) and 118 with single-episode HSV-2 meningitis were included. The progression risk from HSV-2 meningitis to BRLM was 22% (95% confidence interval [CI] 15%-30%). The proportion of patients with the triad of headache, neck stiffness and photophobia/hyperacusis was similar between BRLM and single-episode HSV-2 meningitis (16/43 [37%] vs. 46/103 [45%]; p = 0.41), whilst the median cerebrospinal fluid leukocyte count was lower in BRLM (221 cells vs. 398 cells; p = 0.02). Unfavourable functional outcomes (Glasgow Outcome Scale score of 1-4) were less frequent in BRLM at all post-discharge follow-up visits. During the study period, 10 (21%) patients with BRLM were hospitalized for an additional recurrence (annual rate 6%, 95% CI 3%-12%). The hazard ratio for an additional recurrence was 3.93 (95% CI 1.02-15.3) for patients with three or more previous episodes of meningitis. CONCLUSIONS: Clinical features of BRLM were similar to those of single-episode HSV-2 meningitis, whilst post-discharge outcomes were more favourable. Patients with three or more previous episodes of meningitis had higher risk of an additional recurrence.
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Meningitis Aséptica , Meningitis Viral , Adulto , Humanos , Estudios de Cohortes , Meningitis Viral/epidemiología , Cuidados Posteriores , Reacción en Cadena de la Polimerasa , Recurrencia , Alta del Paciente , Herpesvirus Humano 2/genética , Dinamarca/epidemiologíaRESUMEN
Clinical features applicable to the entire spectrum of viral meningitis are limited, and prognostic factors for adverse outcomes are undetermined. This nationwide population-based prospective cohort study included all adults with presumed and microbiologically confirmed viral meningitis in Denmark from 2015 until 2020. Prognostic factors for an unfavourable outcome (Glasgow Outcome Scale score of 1-4) 30 days after discharge were examined by modified Poisson regression. In total, 1066 episodes of viral meningitis were included, yielding a mean annual incidence of 4.7 episodes per 100 000 persons. Pathogens were enteroviruses in 419/1066 (39%), herpes simplex virus type 2 in 171/1066 (16%), varicella-zoster virus in 162/1066 (15%), miscellaneous viruses in 31/1066 (3%) and remained unidentified in 283/1066 (27%). The median age was 33 years (IQR 27-44), and 576/1066 (54%) were females. In herpes simplex virus type 2 meningitis, 131/171 (77%) were females. Immunosuppression [32/162 (20%)] and shingles [90/149 (60%)] were frequent in varicella-zoster virus meningitis. The triad of headache, neck stiffness and hyperacusis or photophobia was present in 264/960 (28%). The median time until lumbar puncture was 3.0 h (IQR 1.3-7.1), and the median CSF leucocyte count was 160 cells/µl (IQR 60-358). The outcome was unfavourable in 216/1055 (20%) 30 days after discharge. Using unidentified pathogen as the reference, the adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 0.95-1.88) for enteroviruses, 1.55 (95% CI 1.00-2.41) for herpes simplex virus type 2, 1.51 (95% CI 0.98-2.33) for varicella-zoster virus and 1.37 (95% CI 0.61-3.05) for miscellaneous viruses. The adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 1.03-1.75) for females. Timing of acyclovir or valacyclovir was not associated with the outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus. In summary, the outcome of viral meningitis was similar among patients with different aetiologies, including those with presumed viral meningitis but without an identified pathogen. Females had an increased risk of an unfavourable outcome. Early antiviral treatment was not associated with an improved outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus.
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Meningitis Viral , Femenino , Humanos , Adulto , Masculino , Estudios Prospectivos , Pronóstico , Meningitis Viral/epidemiología , Meningitis Viral/tratamiento farmacológico , Herpesvirus Humano 3RESUMEN
Forkhead box protein A2 (FOXA2) is a pioneer transcription factor important for epithelial budding and morphogenesis in different organs. It has been used as a specific marker for uterine glandular epithelial cells (GE). FOXA2 has close interactions with estrogen receptor α (ERα). ERα binding to Foxa2 gene in the uterus indicates its regulation of Foxa2. The intimate interactions between ERα and FOXA2 and their essential roles in early pregnancy led us to investigate the expression of FOXA2 in the female reproductive tract of pre-implantation epiERα-/- (Esr1fl/flWnt7aCre/+) mice, in which ERα is conditionally deleted in the epithelium of reproductive tract. In the oviduct, FOXA2 is detected in the ciliated epithelial cells of ampulla but absent in the isthmus of day 3.5 post-coitum (D3.5) Esr1fl/fl control and epiERα-/- mice. In the uterus, FOXA2 expression in the GE appears to be comparable between Esr1fl/fl and epiERα-/- mice. However, FOXA2 is upregulated in the D0.5 and D3.5 but not PND25-28 epiERα-/- uterine luminal epithelial cells (LE). In the vagina, FOXA2 expression is low in the basal layer and increases toward the superficial layer of the D3.5 Esr1fl/fl vaginal epithelium, but FOXA2 is detected in the basal, intermediate, and superficial layers, with the strongest FOXA2 expression in the intermediate layers of the D3.5 epiERα-/- vaginal epithelium. This study demonstrates that loss of ERα in LE and vaginal basal layer upregulates FOXA2 expression in these epithelial cells during early pregnancy. The mechanisms for epithelial cell-type specific regulation of FOXA2 by ERα remain to be elucidated.
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Receptor alfa de Estrógeno , Útero , Animales , Femenino , Ratones , Embarazo , Epitelio/metabolismo , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Factor Nuclear 3-beta del Hepatocito/genética , Factor Nuclear 3-beta del Hepatocito/metabolismo , Regulación hacia Arriba , Útero/metabolismo , Vagina/metabolismoRESUMEN
Ramsay Hunt syndrome (RHS) is a manifestation of reactivated varicella-zoster virus (VZV) from the geniculate ganglion. Data on clinical features and outcomes of patients with RHS and concurrent VZV meningitis (henceforth RHS meningitis) are limited. Thus, we conducted a nationwide population-based cohort study of all adults hospitalized for RHS meningitis at the departments of infectious diseases in Denmark from 2015 to 2020. Patients with VZV meningitis without cranial nerve palsies were included for comparison. In total, 37 patients with RHS meningitis (mean annual incidence: 1.6/1 000 000 adults) and 162 with VZV meningitis without cranial nerve palsies were included. In RHS meningitis, the median age was 52 years (interquartile range: 35-64), and in addition to peripheral facial nerve palsy (100%), dizziness (46%), and hearing loss (35%) were common symptoms. The triad of headache, neck stiffness, and photophobia/hyperacusis was less common in RHS meningitis than in VZV meningitis without cranial nerve palsies (0/27 [0%] vs. 24/143 [17%]; p = 0.02). At 30 days after discharge, 18/36 (50%) patients with RHS meningitis had persistent peripheral facial nerve palsy, with no statistically significant difference between those treated with and without adjuvant glucocorticoids (6/16 [38%] vs. 12/20 [60%]; p = 0.18). Additional sequelae of RHS meningitis included dizziness (29%), neuralgia (14%), tinnitus/hyperacusis (11%), hearing loss (9%), headache (9%), fatigue (6%), and concentration difficulties (3%). In conclusion, clinical features and outcomes of RHS meningitis were primarily related to cranial neuropathies.
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Varicela , Parálisis Facial , Pérdida Auditiva , Herpes Zóster Ótico , Adulto , Humanos , Persona de Mediana Edad , Herpes Zóster Ótico/complicaciones , Herpes Zóster Ótico/epidemiología , Herpes Zóster Ótico/diagnóstico , Herpesvirus Humano 3/fisiología , Estudios de Cohortes , Mareo , Hiperacusia/complicaciones , Cefalea/complicaciones , Dinamarca/epidemiologíaRESUMEN
OBJECTIVES: The clinical significance of Stenotrophomonas maltophilia in patients with COPD is poorly understood. We aimed to determine whether a lower respiratory tract culture positive for S. maltophilia in COPD patients was independently associated with increased risk of death and hospitalisation for exacerbation of COPD. METHODS: An observational cohort study following outpatients with COPD in Eastern Denmark between 2010 and 2018, with a follow-up period of five years. Presence of S. maltophilia was treated as a time-varying exposure, where patients were considered exposed at the time of the first isolation of S. maltophilia from the lower respiratory tract. The hazard ratio (HR) of death and hospitalisation for acute exacerbations of COPD was assessed using a Cox proportional hazards regression. RESULTS: Of the total 22,689 patients 459 (2.0%) had a lower respiratory sample positive for S. maltophilia. A total of 7,649 deaths (S. maltophilia positive: 243 (52.9%) and S. maltophilia negative: 7,406 (34.4%)) and 24,912 hospitalisations for exacerbation of COPD (S. maltophilia positive: 1,100 in 459 patients and S. maltophilia negative: 23,821 in 22,230 patients) were registered during the study period. We found that a lower respiratory tract culture positive for S. maltophilia was associated with both increased mortality: HR 3.3 (95% CI 2.6-4.3), and hospitalisation for exacerbation of COPD: HR 3.4 (95% CI 2.8-4.1). CONCLUSIONS: A lower respiratory tract culture positive for S. maltophilia in COPD patients was associated with a substantially increased mortality and hospitalisation for exacerbation of COPD. Randomised controlled trials are proposed to determine whether S. maltophilia should be the target of antibiotic treatment.
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Enfermedad Pulmonar Obstructiva Crónica , Stenotrophomonas maltophilia , Humanos , Pacientes Ambulatorios , Estudios de Cohortes , Relevancia Clínica , Enfermedad Pulmonar Obstructiva Crónica/diagnósticoRESUMEN
We use a hybrid superconductor-semiconductor transmon device to perform spectroscopy of a quantum dot Josephson junction tuned to be in a spin-1/2 ground state with an unpaired quasiparticle. Because of spin-orbit coupling, we resolve two flux-sensitive branches in the transmon spectrum, depending on the spin of the quasiparticle. A finite magnetic field shifts the two branches in energy, favoring one spin state and resulting in the anomalous Josephson effect. We demonstrate the excitation of the direct spin-flip transition using all-electrical control. Manipulation and control of the spin-flip transition enable the future implementation of charging energy protected Andreev spin qubits.
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PURPOSE OF THE REVIEW: Hypertension accounts for the largest proportion of cardiovascular (CV) mortality worldwide and its prevalence continues to rise. While prominent CV societies have offered strong recommendations on the management of hypertension in adults, the role of noninvasive CV imaging in the evaluation of hypertensive patients remains incompletely defined. RECENT FINDINGS: Noninvasive imaging is a rapidly expanding field with a growing number of sophisticated and readily applicable modalities to assess how cardiac structure and function changes after periods of sustained, elevated blood pressure. Echocardiography remains the initial modality to screen these patients while developments in nuclear, computed tomography and cardiac magnetic resonance complement and expand investigations for alternative diagnoses that may complement or conflict with the diagnosis of left ventricular hypertrophy. SUMMARY: In this review article, we summarize the application of echocardiography, nuclear imaging, cardiac computed tomography, and cardiac magnetic resonance imaging in the evaluation and management of hypertensive heart disease.
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Cardiopatías , Hipertensión , Humanos , Corazón , Ecocardiografía , Hipertensión/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Imagen por Resonancia MagnéticaRESUMEN
PURPOSE OF REVIEW: To describe the relationship between three pandemics: hypertension, obesity, and heart failure. From pathophysiology to treatment, understanding how these disease entities are linked can lead to breakthroughs in their prevention and treatment. The relevance of this review lies in its discussion of novel pharmacological and surgical treatment strategies for obesity and hypertension, and their role in the prevention and treatment of heart failure. RECENT FINDINGS: Novel medications such as GLP-1 agonists have demonstrated sustained weight loss in patients with obesity, and concurrent improvements in their cardiometabolic profile, and possibly also reductions in hypertension-related comorbidities including heart failure. Surgical therapies including laparoscopic bariatric surgery represent an important treatment strategy in obese patients, and recent studies describe their use even in patients with advanced heart failure, including those with ventricular assist devices. SUMMARY: These developments have deep implications on our efforts to understand, mitigate, and ultimately prevent the three pandemics, and offer promising improvements to quality of life, survival, and the cost burden of these diseases.
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Cirugía Bariátrica , Insuficiencia Cardíaca , Hipertensión , Humanos , Calidad de Vida , Obesidad/terapia , Obesidad/cirugía , Insuficiencia Cardíaca/terapia , Hipertensión/complicaciones , Hipertensión/terapia , Pérdida de PesoRESUMEN
PURPOSE: To describe clinical features and outcomes of viral lumbosacral radiculitis (Elsberg syndrome). METHODS: Nationwide population-based cohort study of all adults hospitalised for viral lumbosacral radiculitis at departments of infectious diseases in Denmark from 2015 to 2020. RESULTS: Twenty-eight patients with viral lumbosacral radiculitis were included (mean annual incidence: 1.2/1,000,000 adults). The median age was 35 years (IQR 27-43), and 22/28 (79%) were female. All patients had urinary retention, with 17/28 (61%) needing a catheter. On admission, at least one sign or symptom of meningitis (headache, neck stiffness, photophobia/hyperacusis) was present in 18/22 (82%). Concurrent genital herpetic lesions were present in 11/24 (46%). The median cerebrospinal fluid leukocyte count was 153 cells/µL (IQR 31-514). Magnetic resonance imaging showed radiculitis/myelitis in 5/19 (26%). The microbiological diagnosis was herpes simplex virus type 2 in 19/28 (68%), varicella-zoster virus in 2/28 (7%), and unidentified in 7/28 (25%). Aciclovir/valaciclovir was administered in 27/28 (96%). At 30 days after discharge, 3/27 (11%) had persistent urinary retention with need of catheter. At 180 days after discharge, moderate disabilities (Glasgow Outcome Scale score of 4) were observed in 5/25 (20%). CONCLUSIONS: Urinary retention resolved within weeks in most patients with viral lumbosacral radiculitis, but moderate disabilities according to the Glasgow Outcome Scale were common at the end of follow-up.
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PURPOSE: In patients surviving infective endocarditis (IE) recurrence of bacteremia or IE is feared. However, knowledge is sparse on the incidence and risk factors for the recurrence of bacteremia or IE. METHODS: Using Danish nationwide registries (2010-2020), we identified patients with first-time IE which were categorized by bacterial species (Staphylococcus aureus, Enterococcus spp., Streptococcus spp., coagulase-negative staphylococci [CoNS], 'Other' microbiological etiology). Recurrence of bacteremia (including IE episodes) or IE with the same bacterial species was estimated at 12 months and 5 years, considering death as a competing risk. Cox regression models were used to compute adjusted hazard ratios of the recurrence of bacteremia or IE. RESULTS: We identified 4086 patients with IE; 1374 (33.6%) with S. aureus, 813 (19.9%) with Enterococcus spp., 1366 (33.4%) with Streptococcus spp., 284 (7.0%) with CoNS, and 249 (6.1%) with 'Other'. The overall 12-month incidence of recurrent bacteremia with the same bacterial species was 4.8% and 2.6% with an accompanying IE diagnosis, while this was 7.7% and 4.0%, respectively, with 5 years of follow-up. S. aureus, Enterococcus spp., CoNS, chronic renal failure, and liver disease were associated with an increased rate of recurrent bacteremia or IE with the same bacterial species. CONCLUSION: Recurrent bacteremia with the same bacterial species within 12 months, occurred in almost 5% and 2.6% for recurrent IE. S. aureus, Enterococcus spp., and CoNS were associated with recurrent infections with the same bacterial species.
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Bacteriemia , Endocarditis Bacteriana , Endocarditis , Infecciones Estafilocócicas , Humanos , Staphylococcus aureus , Endocarditis Bacteriana/epidemiología , Endocarditis Bacteriana/microbiología , Bacterias , Infecciones Estafilocócicas/microbiología , Bacteriemia/epidemiología , Bacteriemia/microbiología , Staphylococcus , Enterococcus , StreptococcusRESUMEN
Anti-SSA-autoantibodies are common in patients with rheumatologic disease, especially Sjögren's syndrome, systemic lupus erythematosus and rheumatoid arthritis. They consist of both autoantibodies towards Ro60 and Ro52, the latter also known as TRIM21. TRIM21 is an intracellular protein consisting of four domains; PRY/SPRY, Coiled-Coil, B-box and RING. The aim of this study was to establish an indirect ELISA detecting autoantibodies towards both the full-length TRIM21 protein and its four domains. We expressed the five constructs, created, and validated indirect ELISA protocols for each target using plasma from anti-SSA positive patients and healthy controls. Our findings were validated to the clinically used standards. We measured significantly higher levels of autoantibodies towards our full-length TRIM21, and the PRY/SPRY, Coiled-Coil and RING domains in patients compared to healthy controls. No significant difference in the level of autoantibodies were detected against the B-box domain. Our setups had a signal to noise ratio in the range of 30 to 184, and an OD between 2 and 3. Readings did not decline using NaCl of 500 mM as wash, affirming the high binding affinity of the autoantibodies measured. Our protocols allow us to further study the different autoantibodies of anti-SSA positive patients. This creates the possibility to stratify our patients into subgroups regarding autoantibody profile and specific pheno- or endotype.
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Lupus Eritematoso Sistémico , Síndrome de Sjögren , Humanos , Autoanticuerpos , Síndrome de Sjögren/diagnóstico , Lupus Eritematoso Sistémico/diagnóstico , Autoantígenos , Dominios Proteicos , Ensayo de Inmunoadsorción EnzimáticaRESUMEN
BACKGROUND: There is a significantly higher number of people experiencing severe levels of suicidal thoughts compared to that of suicidal deaths and suicide attempts. In suicide prevention research, there is a shift towards greater emphasis on people's experiences of living with suicidal thoughts. This can expand the existing evidence base, which is dominated by a biomedical approach. The aim of this review was to summarise and disseminate existing research on the lived experiences of living with suicidal thoughts. METHODS: A scoping review by Arksey & O'Malley consisting of six stages: (1) formulating the research question, (2) identifying relevant studies, (3) selecting studies, (4) mapping data, (5) summarising the results and (6) consulting stakeholders. PubMed, PsycINFO and CINAHL were searched for studies in English, Danish, Swedish and Norwegian. Peer-reviewed articles examining people's experiences of living with suicidal thoughts using qualitative methods were included. The search was supplemented with a citation pearl search in the Web of Science database. Twenty-eight studies were included. RESULTS: The findings were organised under two thematic headings: (a) the significance of social connections and (b) a loss of the personal self. CONCLUSION: There is a need for further qualitative research of people's experiences of living with suicidal thoughts from an everyday life perspective. Awareness about social connections and attachment in mental health prevention and governance is crucial. Trauma-informed care could be a useful approach to prevent suicidal thoughts as the review found that many participants had traumatic experiences in both childhood and adulthood. As part of the treatment of suicidal thoughts, it might be useful to have a focus on narrative and communicative methods and their clinical application.
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Ideación Suicida , Intento de Suicidio , Humanos , Niño , Intento de Suicidio/psicología , Salud Mental , Prevención del Suicidio , NarraciónRESUMEN
OBJECTIVE: To investigate differences in bacterial distribution and resistance patterns of relevant pathogens in skin and tissue infections among migrants compared to nonmigrants. METHODS: The population is based on a cohort of migrants who obtained residence as refugees or family-reunited migrants in Denmark between January 1993 and December 2015. The cohort was linked to positive swabs and tissue cultures collected from hospitals and general practitioners between the years 2000 and 2016 at the Department of Microbiology, University Hospital Hvidovre, Denmark. We calculated odds ratios for pathogen distribution and resistance patterns using logistic regression by comparing migrants with nonmigrants. RESULTS: In total, 43,770 pathogens from 37,276 individuals were included, with Staphylococcus aureus being the most common bacterium. Migrants had higher odds of infections with Enterobacterales than nonmigrants (OR 1.42, 95% CI: 1.23-1.63) and lower odds of beta-haemolytic Streptococci (OR 0.79, 95% CI: 0.73-0.86). Family-reunited migrants and refugees had higher odds of methicillin-resistant S. aureus (MRSA) than nonmigrants (OR 5.01, 95% CI: 3.73-6.73 and OR 3.66, 95% CI: 2.61-5.13). This was more pronounced in female migrants. The odds of ciprofloxacin-resistant Enterobacterales were higher in both family-reunited migrants and refugees than in nonmigrants (OR 2.21, 95% CI: 1.34-3.64 and OR 2.17, 95% CI: 1.34-3.52). CONCLUSIONS: The prevalence of MRSA and ciprofloxacin-resistant Enterobacterales was higher among family-reunited migrants and refugees than in nonmigrants. Our findings suggest an increased awareness for AMR in migrants.
Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Migrantes , Femenino , Humanos , Estudios Transversales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana , Infecciones Estafilocócicas/microbiología , Ciprofloxacina , Dinamarca/epidemiologíaRESUMEN
BACKGROUND: Post-operative pain amelioration following breast cancer surgery is inconsistent. The novel multiple-injection costotransverse block (MICB) mimics the thoracic paravertebral block by possible anaesthetising the ventral rami of the thoracic spinal nerves and the sympathetic trunk. Proof of concept has been determined in a cadaveric study and needs further clinical testing. METHODS: This double-blinded, randomised and placebo-controlled study investigates the efficacy of the ultrasound-guided MICB versus placebo in 36 patients undergoing unilateral mastectomy and primary subpectoral reconstruction surgery. Oral pre-operative medicine is standardised for all patients. Active group is pre-operatively administered MICB with three injections of each 10 ml of ropivacaine (5 mg/ml). The placebo group is pre-operatively administered three injections of each 10 ml of saline (0.9%). Standard general anaesthesia is induced and 30 min before emergence 0.2 µg/kg total body weight sufentanil IV, 1 g of paracetamol IV and 4 mg of ondansetron IV (post-operative nausea and vomiting, PONV, prophylaxis) will be administered. All patients are provided with a patient-controlled analgesia pump with morphine. The primary aim is total morphine consumption in the first 24 post-operative hours. Secondary aims are pain intensity, duration of the block, patient satisfaction, side effects, time to ambulation, time to discharge, and quality of recovery. DISCUSSION: Recruitment began in November 2019 and is expected to finish ultimo 2021. Results are expected to be published in an international peer-reviewed medical journal. The results will hopefully provide a substantial contribution to the knowledge of these new 'intertransverse process blocks' providing regional anaesthesia of the thoracic wall.