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This systematic review aims to identify the sleep parameters of Olympic athletes and the instruments used to assess and monitor the sleep of these athletes. The search was conducted until February 2023 and was performed in PubMed, Web of Science, and Scopus databases. This systematic review has included studies that investigated at least one of the following sleep parameters: total sleep time (TST), sleep onset latency (SOL), sleep efficiency (SE), awakenings after sleep onset (WASO), quality of sleep, daytime sleepiness, and chronotype; the participants were Olympic athletes. The search returned a total of 280 studies. After screening based on exclusion and inclusion criteria, 11 studies were included. The main results demonstrate that Olympic athletes have TST of 06:10 h, SE of 84%, SOL of 28 min, and WASO of 49 min. The most predominant chronotype is indifferent; over half of the athletes have poor sleep quality and complaints. Furthermore, actigraphy was the most used method to assess sleep. It is concluded that Olympic athletes have TST, SE, and WASO poor than the recommended values. In addition, sleep complaints and poor sleep quality were also observed. Among the objective sleep assessment methods, actigraphy was the method most frequently used in this population.
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Actigrafia , Atletas , Sono , Humanos , Actigrafia/instrumentação , Sono/fisiologia , Qualidade do Sono , Latência do Sono/fisiologia , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/fisiopatologia , Fatores de Tempo , Esportes/fisiologiaRESUMO
OBJECTIVES: Patient global assessment (PGA) is purported to add the patient's perspective in the composite measures of RA. However, PGA is not standardized and it is not known whether patients' interpretation of the measure is consistent with its intended purpose. This study aimed to explore difficulties experienced by patients with RA in completing PGA, and to assess the impact of a structured explanation in improving its validity and reliability. METHODS: This was a mixed methods study, using interviews, focus groups and PGA data. During interviews, patients (convenience sample, n = 33) completed three often-used PGA formulations. Then a nurse provided structured explanation about what PGA is and why it is used. After further discussion, patients completed one PGA version again. Interviews were recorded, transcribed and analysed using inductive thematic analysis. We compared PGA scores pre- and post-explanation (Wilcoxon signed-ranks) and the proportion of patients achieving RA remission with PGA ⩽1 (McNemar's tests). RESULTS: Three themes emerged: understanding the meaning of PGA, the purpose of PGA and measurement difficulties. The difficulties caused systematic errors in PGA completion such as marking higher when feeling well, marking near the centre or away from zero. The structured explanation was helpful. Following the explanation, the median PGA score decreased from 3.0 to 2.1 cm, and the proportion of non-remission solely due to PGA >1 from 52% to 41%; none of these changes was statistically significant. CONCLUSION: Many patients have difficulties in completing PGA. Standardization of PGA and a structured explanation may improve its clarity, validity and reliability.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Saúde Global , Medidas de Resultados Relatados pelo Paciente , Adulto , Artrite Reumatoide/diagnóstico , Feminino , Grupos Focais , Humanos , Incidência , Internacionalidade , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Medição de Risco , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
The surgical treatment of dentofacial deformities is performed routinely and predictably in dentate patients. However, when dealing with the edentulous maxilla, treatment becomes more challenging and less predictable. In these cases, the combination of orthognathic surgery and osseointegrated implants could be a viable alternative to enable fixed rehabilitation. A patient with an edentulous and atrophic maxilla with maxillomandibular discrepancy and high esthetic requirement was treated with a combination of osseointegrated implants and orthognathic surgery. The rehabilitative sequence was composed of maxillary grafting procedures, installation of dental implants, placement of a fixed implant-supported prosthesis, and bimaxillary orthognathic surgery. During provisional restoration before orthognathic surgery, smaller teeth were used, allowing achievement of appropriate tooth length for the final restoration, even after natural and expected postoperative relapse. This restorative approach provided an implant-supported fixed prosthesis without prosthetic compensation and with optimum esthetics and biomechanics.
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Implantes Dentários , Arcada Edêntula/patologia , Arcada Edêntula/cirurgia , Maxila/patologia , Maxila/cirurgia , Cirurgia Ortognática , Adulto , Atrofia , Implantação Dentária Endóssea , Prótese Dentária Fixada por Implante , Estética Dentária , Feminino , HumanosRESUMO
This article reports on a new class of stimuli-responsive surfactant generated from commercially available amphiphiles such as dodecyltrimethylammmonium bromide (DTAB) by substitution of the halide counterion with counterions such as 2-cyanopyrrolide, 1,2,3-triazolide, and L-proline that complex reversibly with CO2. Through a combination of small-angle neutron scattering (SANS), electrical conductivity measurements, thermal gravimetric analysis, and molecular dynamics simulations, we show how small changes in charge reorganization and counterion shape and size induced by complexation with CO2 allow for fine-tunability of surfactant properties. We then use these findings to demonstrate a range of potential practical uses, from manipulating microemulsion droplet morphology to controlling micellar and vesicular aggregation. In particular, we focus on the binding of these surfactants to DNA and the reversible compaction of surfactant-DNA complexes upon alternate bubbling of the solution with CO2 and N2.
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Facial nerve has great functional and aesthetic importance to the face, and damage to its structure can lead to major complications. This article reports a clinical case of neuroanastomosis of the facial nerve after facial trauma, describing surgical procedure and postoperative follow-up. A trauma patient with extensive injury cut in right mandibular body causing neurotmesis of the VIIth cranial nerve and mandibular angle fracture right side was treated. During surgical exploration, the nerve segments were identified and a neuroanastomosis was performed using nylon 10-0, after reduction and internal fixation of the mandibular fracture. Postoperatively, an 8-month follow-up showed good evolution and preservation of motor function of the muscles of facial mime, highlighting the success of the surgical treatment. Nerve damage because of facial trauma can be a surgical treatment challenge, but when properly conducted can functionally restore the damaged nerve.
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Traumatismos do Nervo Facial/etiologia , Nervo Facial/diagnóstico por imagem , Paralisia Facial/etiologia , Fixação Interna de Fraturas/efeitos adversos , Fraturas Mandibulares/cirurgia , Procedimentos Neurocirúrgicos/métodos , Adolescente , Traumatismos do Nervo Facial/diagnóstico , Traumatismos do Nervo Facial/cirurgia , Paralisia Facial/diagnóstico , Paralisia Facial/cirurgia , Feminino , Fixação Interna de Fraturas/métodos , Humanos , Mandíbula/cirurgia , Côndilo Mandibular/cirurgia , Fraturas Mandibulares/complicações , Fraturas Mandibulares/diagnóstico , Procedimentos de Cirurgia PlásticaRESUMO
OBJECTIVES: The task force aimed to: (1) develop evidence-based recommendations for patient education (PE) for people with inflammatory arthritis, (2) identify the need for further research on PE and (3) determine health professionals' educational needs in order to provide evidence-based PE. METHODS: A multidisciplinary task force, representing 10 European countries, formulated a definition for PE and 10 research questions that guided a systematic literature review (SLR). The results from the SLR were discussed and used as a basis for developing the recommendations, a research agenda and an educational agenda. The recommendations were categorised according to level and strength of evidence graded from A (highest) to D (lowest). Task force members rated their agreement with each recommendation from 0 (total disagreement) to 10 (total agreement). RESULTS: Based on the SLR and expert opinions, eight recommendations were developed, four with strength A evidence. The recommendations addressed when and by whom PE should be offered, modes and methods of delivery, theoretical framework, outcomes and evaluation. A high level of agreement was achieved for all recommendations (mean range 9.4-9.8). The task force proposed a research agenda and an educational agenda. CONCLUSIONS: The eight evidence-based and expert opinion-based recommendations for PE for people with inflammatory arthritis are intended to provide a core framework for the delivery of PE and training for health professionals in delivering PE across Europe.
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Artrite , Educação de Pacientes como Assunto/normas , Doenças Reumáticas , Reumatologia/normas , Comitês Consultivos , Artrite Reumatoide , Competência Clínica , Europa (Continente) , Medicina Baseada em Evidências , Humanos , Reumatologia/educação , Espondilite AnquilosanteRESUMO
PURPOSE: The aim of this study was to evaluate deformation, roughness, and mass loss of stainless steel, diamond-like carbon (DLC)-coated and zirconia drills after multiple osteotomies with sterilization procedures. MATERIALS AND METHODS: Drilling procedures were performed using stainless steel (G1), DLC-coated (G2), and zirconia (G3) drills. All groups were divided in subgroups 1, 2, 3, 4, and 5, corresponded to drills used 0, 10, 20, 30, and 40 times, respectively. RESULTS: No significant differences in mass and roughness were detected among all groups and subgroups. In SEM images, all groups revealed signs of wear while coating delamination was detected in G2. Drills from G1 displayed more irregular surface, whereas cutting edges were more regular in G3. CONCLUSION: Zirconia drills presented more regular surfaces whereas stainless steel drills revealed more severe signs of wear. Further studies must be performed to evaluate the putative influence of these findings in heat generation.
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Instrumentos Odontológicos , Osteotomia/métodos , Esterilização , Animais , Bovinos , Implantação Dentária/métodos , Instrumentos Odontológicos/efeitos adversos , Diamante , Humanos , Costelas/cirurgia , ZircônioRESUMO
Sleep problems are common in individuals with low back pain (LBP) and sleep restriction seems to be associated with impaired pain processing. Our objective was to investigate whether sleep is associated with future LBP outcomes (i.e. pain intensity, disability, and recovery) in adults. We conducted a systematic review of prospective cohort studies and secondary analyses of randomized controlled trials (registration-PROSPERO CRD42022370781). In December 2022, we searched the MEDLINE, Embase, CINAHL, and PsycINFO databases. Fourteen studies, totaling 19 170 participants were included. Thirteen studies were rated as having high risk of bias (QUIPS tool). We used vote-counting and meta-analysis approaches to synthesize the data. We found associations between baseline sleep with future pain intensity, recovery, and between changes in sleep with changes in pain intensity, changes in disability, and recovery. We further synthesized outcomes as "overall LBP improvement" outcomes. Baseline poor sleep was moderately associated with non-improvement in LBP in the long-very long term (OR 1.55, 95% CI: 1.39 to 1.73; three studies providing unadjusted effect sizes), and non-improvement in sleep was largely associated with non-improvement in LBP in the short-moderate term (OR 3.45, 95% CI: 2.54 to 4.69; four studies providing unadjusted effect sizes). We found no association between baseline sleep with future disability and overall LBP improvement in the short-moderate term. Therefore, sleep may be a prognostic factor for pain intensity and recovery from LBP. All findings were supported by low to very low-quality evidence. Better-conducted studies are needed to strengthen our certainty about the evidence.
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Dor Lombar , Ensaios Clínicos Controlados Aleatórios como Assunto , Dor Lombar/fisiopatologia , Humanos , Prognóstico , Estudos Prospectivos , Transtornos do Sono-Vigília/fisiopatologia , Sono/fisiologiaRESUMO
Loss of an upper limb exerts a negative influence on an individual's ability to perform their activities of daily living (ADLs), reducing quality of life and self-esteem. A prosthesis capable of performing basic ADLs functions has the capability of restoring independence and autonomy to amputees. However, current technologies present in robotic prostheses are based on rigid actuators with several drawbacks, such as high weight and low compliance. Recent advances in robotics have allowed for the development of flexible actuators and artificial muscles to overcome the limitations of rigid actuators. Dielectric elastomer actuators (DEAs) consist of a thin elastomer membrane arranged between two compliant electrodes capable of changing dimensions when stimulated with an electrical potential difference. In this work, we present the design and testing of a finger prosthesis driven by two DEAs arranged as agonist-antagonist pairs as artificial muscles. The soft actuators are designed as fiber-constrained dielectric elastomers (FCDE), enabling displacement in just one direction as natural muscles. The finger prosthesis was designed and modeled to show bend movement using just one pair of DEAs and was made of PLA in an FDM 3D printer to be lightweight. The experimental results show great agreement with the proposed model and indicate that the proposed finger prosthesis is promising in overcoming the limitations of the current rigid based actuators.
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BACKGROUND: Lepidopteran pest control in agriculture has become heavily dependent on cultivars that express Bacillus thuringiensis (Bt) toxins as 'plant-incorporated protectants'. However, populations of Spodoptera frugiperda (Smith) in Brazil appear resistant to the Bt traits currently available in commercial soybean cultivars. RESULTS: This study evaluated S. frugiperda life history when feeding on three different Bt soybean cultivars. Cultivars expressing Cry1Ac + Cry1F and Cry1A.105 + Cry2Ab2 + Cry1Ac Bt toxins caused 100% larval mortality in S. frugiperda. Both non-Bt and Cry1Ac-expressing soybean induced transgenerational effects that increased the survival of subsequent generations. A Cry1Ac soybean diet reduced the generation time (T) of S. frugiperda relative to non-Bt soybean, resulting in shorter generation time and more rapid population growth. CONCLUSION: The implications of these results revealed how diet can alter aspects of insect life history and biology, and have important implications for sustainable management of S. frugiperda on soybean. © 2024 Society of Chemical Industry.
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BACKGROUND: Recent studies show Silent Myocardial Infarction (SMI) as a quite frequent event. However, regarding severe tertiary care patients that frequently present consequences of Coronary Artery Disease (CAD) and Left Ventricular Dysfunction (LVD), the occurrence of this manifestation is unexpected and its associated factors aren't clear in the literature. AIM: To compare clinical, laboratorial, ventricular and angiographic factors between silent and classical presentation of MI in patients with CAD and LVD. METHODS: Patients with multivessel CAD with over 70 % obstructive lesions and LVD with EF less than 35 % were evaluated for MASS VI trial and later included in the present study. The ventricular function and coronary assessment were measured by echocardiography and SYNTAX score, respectively. The population was stratified in a SMI group and Clinically Manifested Myocardial Infarction (CMMI) group based on MI presentation for a comparison of medical parameters. RESULTS: From 132 patients, 47 (35.6 %) were classified as SMI and 85 (64.4 %) as CMMI. No differences were observed between groups regarding age, sex, diabetes mellitus, SYNTAX score, or collateral circulation. Higher proportion of NYHA II classification, inferior wall MI and lower creatinine clearance were found in SMI group. After multivariate analysis, peripheral diabetic neuropathy (OR = 4.6 [1.1â12.7] p = 0.032) and inferior wall MI (OR = 4.1 [1.5â11.4] p = 0.007) were significantly associated with SMI. CONCLUSION: Peripheral diabetic neuropathy and inferior wall MI were associated with SMI presentation. Overall, associated factors tend to be similar comparing SMI and CMMI, but in the specific population of diabetic patients with chronic neuropathy a special care should be taken.
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Angiografia Coronária , Insuficiência Cardíaca , Infarto do Miocárdio , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Estudos de Casos e Controles , Idoso , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/complicações , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/etiologia , Fatores de Risco , Ecocardiografia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Isquemia Miocárdica/complicações , Isquemia Miocárdica/diagnóstico por imagemRESUMO
Hypervirulence and carbapenem-resistant have emerged as two distinct evolutionary pathotypes of Klebsiella pneumoniae, with both reaching their epidemic success and posing a great threat to public health. However, as the boundaries separating these two pathotypes fade, we assist a worrisome convergence in certain high-risk clones, causing hospital outbreaks and challenging every therapeutic option available. To better understand the basic biology of these pathogens, this review aimed to describe the virulence factors and their distribution worldwide among carbapenem-resistant highly virulent or hypervirulent K. pneumoniae strains, as well as to understand the interplay of these virulence strains with the carbapenemase produced and the sequence type of such strains. As we witness a shift in healthcare settings where carbapenem-resistant highly virulent or hypervirulent K. pneumoniae are beginning to emerge and replace classical K. pneumoniae strains, a better understanding of these strains is urgently needed for immediate and appropriate response.
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Background: Normal pressure hydrocephalus is a disease directly related to the change in intracranial compliance and consequent repercussions in the brain parenchyma. Invasive monitoring of such parameters proves to be reliable especially for prognosis in neurocritical patients; however, it is not applicable in an outpatient service setting. The present study describes the comparison between the tap test results and the parameters obtained with a non-invasive sensor for monitoring intracranial compliance in patients with suspected NPH. Methods: Twenty-eight patients were evaluated before and after lumbar puncture of 50mL of CSF (the tap test), comprising clinical assessment, magnetic resonance imaging, physical therapy assessment using the Timed Up and Go test, Dynamic Gait Index, BERG test, neuropsychological assessment, and recording of non-invasive intracranial compliance data using the Brain4care® device in three different positions (lying, sitting, and standing) for 5 min each. The tap test results were compared to the Time to Peak and P2/P1 ratio parameters obtained by the device. Results: The group that had a positive Tap test result presented a median P2/P1 ratio greater than 1.0, suggesting a change in intracranial compliance. In addition, there was also a significant difference between patients with positive, negative, and inconclusive results, especially in the lying position. Conclusion: A non-invasive intracranial compliance device when used with the patient lying down and standing up obtained parameters that suggest correspondence with the result of the tap test.
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This study aimed to evaluate B[a]P and low-density polyethylene microplastics (MPs) toxicty, alone and in mixture (0.03 to 30 µg L-1 of B[a]P; and 5, 50 and 500 mg L-1 for MPs). Five mg L-1 of MPs is considerably higher than commonly reported environmental concentrations, although it has been reported for marine environments. Individual (sea urchin embryo-larval development and mortality of mysids) and sub-individual responses (LPO and DNA damage in mysids) were assessed. The toxicity increased as the B[a]P concentration increased, and microplastics alone did not cause toxicity. B[a]P toxicity was not modified by the lowest concentration of MPs (5 mg L-1), but at higher MPs concentrations (50 and 500 mg L-1), the effects of B[a]P on sea urchin development and in biomarkers in mysids were diminished. Microplastics interacted with B[a]P in seawater, reducing its toxicity, probably due to adsorption of B[a]P to the surface of microplastics.
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Microplásticos , Poluentes Químicos da Água , Animais , Microplásticos/toxicidade , Plásticos/toxicidade , Benzo(a)pireno/toxicidade , Organismos Aquáticos , Invertebrados , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análiseRESUMO
Liver cancer involves tumor cells rapidly growing within a packed tissue environment. Patient tumor tissues reveal densely packed and deformed cells, especially at tumor boundaries, indicative of physical crowding and compression. It is not well understood how these physical signals modulate tumor evolution and therapeutic susceptibility. Here we investigate the impact of volumetric compression on liver cancer (HepG2) behavior. We find that conditioning cells under a highly compressed state leads to major transcriptional reprogramming, notably the loss of hepatic markers, the epithelial-to-mesenchymal transition (EMT)-like changes, and altered calcium signaling-related gene expression, over the course of several days. Biophysically, compressed cells exhibit increased Rac1-mediated cell spreading and cell-extracellular matrix interactions, cytoskeletal reorganization, increased YAP and ß-catenin nuclear translocation, and dysfunction in cytoplasmic and mitochondrial calcium signaling. Furthermore, compressed cells are resistant to chemotherapeutics and desensitized to apoptosis signaling. Apoptosis sensitivity can be rescued by stimulated calcium signaling. Our study demonstrates that volumetric compression is a key microenvironmental factor that drives tumor evolution in multiple pathological directions and highlights potential countermeasures to re-sensitize therapy-resistant cells. Significance statement: Compression can arise as cancer cells grow and navigate within the dense solid tumor microenvironment. It is unclear how compression mediates critical programs that drive tumor progression and therapeutic complications. Here, we take an integrative approach in investigating the impact of compression on liver cancer. We identify and characterize compressed subdomains within patient tumor tissues. Furthermore, using in vitro systems, we induce volumetric compression (primarily via osmotic pressure but also via mechanical force) on liver cancer cells and demonstrate significant molecular and biophysical changes in cell states, including in function, cytoskeletal signaling, proliferation, invasion, and chemoresistance. Importantly, our results show that compressed cells have impaired calcium signaling and acquire resistance to apoptosis, which can be countered via calcium mobilization.
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New Delhi metallo-ß-lactamase (NDM) carbapenemase has been considered a global threat due to its worldwide widespread in recent years. In Portugal, a very low number of infections with NDM-producing Enterobacterales has been reported. A total of 52 strains from 40 patients and 1 environmental sample isolated during COVID-19 pandemic were included in this study. Wholegenome sequencing (WGS) was performed on 20 carbapenemase-producing strains, including 17 NDM-1-producing Klebsiella pneumoniae ST11-KL105 lineage strains, one NDM-1-producing Escherichia coli ST58 strain and one KPC-3-producing K. pneumoniae ST147 strain, recovered from a total of 19 patients. Of interest, also one NDM-1-producing K. pneumoniae ST11-KL105 was collected from the hospital environment. Genome-wide phylogenetic analysis revealed an ongoing dissemination of NDM-1-producing K. pneumoniae ST11 strains (n = 18) with the same genetic features seen across multiple wards. Furthermore, the ST58 E. coli strain, collected from a patient rectal swab that was also colonised with a K. pneumoniae strain, also showed the IncFIA plasmid replicon and the blaNDM-1 gene (preceded by IS30 and followed by genes bleMBL, trpF, dsbC, cutA, groES and groEL). The blaNDM-1 is part of Tn125-like identical to those reported in Poland, Italy and India. The blaKPC-3 K. pneumoniae ST147-KL64 strain has the genetic environment Tn4401d isoform. In conclusion, herein we report the molecular epidemiology, resistome, virulome and mobilome of the first NDM-1 carbapenemase outbreak caused by K. pneumoniae ST11-KL105 lineage during the COVID-19 pandemic in Portugal. Moreover, the outbreak strains characterised included seventeen different patients (infected and colonised) and one environmental sample which also emphasises the role of commensal and hospital environment strains in the dissemination of the outbreak.
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The combination of ceftazidime/avibactam (CZA) is a novel ß-lactam/ß-lactamase inhibitor with activity against Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales. Emerging cases caused by CZA-resistant strains that produce variants of KPC genes have already been reported worldwide. However, to the best of our knowledge, no CZA-resistant strains were reported in Portugal. In September 2019, a K. pneumoniae CZA-resistant strain was collected from ascitic fluid at a surgery ward of a tertiary University Hospital Center in Lisboa, Portugal. The strain was resistant to ceftazidime/avibactam, as well as to ceftazidime, cefoxitin, gentamicin, amoxicillin/clavulanic acid, and ertapenem, being susceptible to imipenem and tigecycline. A hypermucoviscosity phenotype was confirmed by string test. Whole-genome sequencing (WGS) analysis revealed the presence of an ST13 KPC70-producing K. pneumoniae, a KPC-3 variant, differing in two amino-acid substitutions (D179Y and T263A). The D179Y mutation in the KPC Ω-loop region is the most common amino-acid substitution in KPC-2 and KPC-3, further leading to CZA resistance. The second mutation causes a KPC-70 variant in which threonine replaces alanine (T263A). The CZA-resistant strain showed the capsular locus KL3 and antigen locus O1v2. Other important virulence factors were identified: fimbrial adhesins type 1 and type 3, as well as the cluster of iron uptake systems aerobactin, enterobactin, salmochelin, and yersiniabactin included in integrative conjugative element 10 (ICEKp10) with the genotoxin colibactin cluster. Herein, we report the molecular characterization of the first hypervirulent CZA-resistant ST13 KPC-70-producing K. pneumoniae strain in Portugal. The emergence of CZA-resistant strains might pose a serious threat to public health and suggests an urgent need for enhanced clinical awareness and epidemiologic surveillance.
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The carbapenem-resistant Enterobacterales (CRE) strains have been identified by the World Health Organization as critical priority pathogens in research and development of diagnostics, treatments, and vaccines. However, recent molecular information about carbapenem-resistant K. pneumoniae (CRK) epidemiology in Portugal is still scarce. Thus, this study aimed to provide the molecular epidemiology, resistome, and virulome of CRK clinical strains recovered from a tertiary care hospital centre (2019-2021) using polymerase chain reaction (PCR) and the advanced molecular technique whole-genome sequencing (WGS). PCR amplification of carbapenemase genes was performed in 437 carbapenem-resistant K. pneumoniae strains. The most frequent carbapenemases were: KPC-3 (42%), followed by OXA-181 (20%), GES-5 (0.2%), and NDM-1 (0.2%). Additionally, 10 strains (2%) coproduced KPC-3 and OXA-181, and 1 strain coproduced KPC-3 and OXA-48 (0.2%). The genomic population structure of 68 strains characterized by WGS demonstrated the ongoing dissemination of four main high-risk clones: ST13, ST17, ST147, and ST307, while no clones belonging to the European predominant clonal groups (CG15 and CG258) were found. Moreover, we describe one K. pneumoniae ST39-KL62 that coproduced the NDM-1 carbapenemase and the extended-spectrum beta-lactamase CTX-M-15, and one K. pneumoniae ST29-KL54 GES-5 and BEL-1 coproducer. Furthermore, a high prevalence of iron siderophores were present in all CRK strains, with several strains presenting both colibactin and the hypermucoviscosity phenotype. Thus, the data presented here highlight an uncommon molecular epidemiology pattern in Portugal when compared with most European countries, further supporting the emergence and dissemination of nonclonal group 258 hypervirulent multidrug high-risk clones and the need to promote in-depth hospital molecular surveillance studies.
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Patients infected by the SARS-CoV-2 virus are commonly diagnosed with threatening liver conditions associated with drug-induced therapies and systemic viral action. RNA-Seq data from cells in bronchoalveolar lavage fluid from COVID-19 patients have pointed out dysregulation of kallikrein-kinin and renin-angiotensin systems as a possible mechanism that triggers multi-organ damage away from the leading site of virus infection. Therefore, we measured the plasma concentration of biologically active peptides from the kallikrein-kinin system, bradykinin and des-Arg9-bradykinin, and liver expression of its proinflammatory axis, bradykinin 1 receptor (B1R). We measured the plasma concentration of bradykinin and des-Arg9-bradykinin of 20 virologically confirmed COVID-19 patients using a liquid chromatography-tandem mass spectrometry-based methodology. The expression of B1R was evaluated by immunohistochemistry from post-mortem liver specimens of 27 COVID-19 individuals. We found a significantly higher blood level of des-Arg9-bradykinin and a lower bradykinin concentration in patients with COVID-19 compared to a healthy, uninfected control group. We also observed increased B1R expression levels in hepatic tissues of patients with COVID-19 under all hepatic injuries analyzed (liver congestion, portal vein dilation, steatosis, and ischemic necrosis). Our data indicate that des-Arg9-bradykinin/B1R is associated with the acute hepatic dysfunction induced by the SARS-CoV-2 virus infection in the pathogenesis of COVID-19.