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1.
Development ; 151(4)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38381702

RESUMO

The liver restores its mass and architecture after injury. Yet, investigating morphogenetic cell behaviours and signals that repair tissue architecture at high spatiotemporal resolution remains challenging. We developed LiverZap, a tuneable chemoptogenetic liver injury model in zebrafish. LiverZap employs the formation of a binary FAP-TAP photosensitiser followed by brief near-infrared illumination inducing hepatocyte-specific death and recapitulating mammalian liver injury types. The tool enables local hepatocyte ablation and extended live imaging capturing regenerative cell behaviours, which is crucial for studying cellular interactions at the interface of healthy and damaged tissue. Applying LiverZap, we show that targeted hepatocyte ablation in a small region of interest is sufficient to trigger local liver progenitor-like cell (LPC)-mediated regeneration, challenging the current understanding of liver regeneration. Surprisingly, the LPC response is also elicited in adjacent uninjured tissue, at up to 100 µm distance to the injury. Moreover, dynamic biliary network rearrangement suggests active cell movements from uninjured tissue in response to substantial hepatocyte loss as an integral step of LPC-mediated liver regeneration. This precisely targetable liver cell ablation tool will enable the discovery of key molecular and morphogenetic regeneration paradigms.


Assuntos
Sistema Biliar , Peixe-Zebra , Animais , Regeneração Hepática/fisiologia , Hepatócitos , Fígado/metabolismo , Mamíferos
2.
Proc Natl Acad Sci U S A ; 121(25): e2314036121, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38857391

RESUMO

Permafrost regions contain approximately half of the carbon stored in land ecosystems and have warmed at least twice as much as any other biome. This warming has influenced vegetation activity, leading to changes in plant composition, physiology, and biomass storage in aboveground and belowground components, ultimately impacting ecosystem carbon balance. Yet, little is known about the causes and magnitude of long-term changes in the above- to belowground biomass ratio of plants (η). Here, we analyzed η values using 3,013 plots and 26,337 species-specific measurements across eight sites on the Tibetan Plateau from 1995 to 2021. Our analysis revealed distinct temporal trends in η for three vegetation types: a 17% increase in alpine wetlands, and a decrease of 26% and 48% in alpine meadows and alpine steppes, respectively. These trends were primarily driven by temperature-induced growth preferences rather than shifts in plant species composition. Our findings indicate that in wetter ecosystems, climate warming promotes aboveground plant growth, while in drier ecosystems, such as alpine meadows and alpine steppes, plants allocate more biomass belowground. Furthermore, we observed a threefold strengthening of the warming effect on η over the past 27 y. Soil moisture was found to modulate the sensitivity of η to soil temperature in alpine meadows and alpine steppes, but not in alpine wetlands. Our results contribute to a better understanding of the processes driving the response of biomass distribution to climate warming, which is crucial for predicting the future carbon trajectory of permafrost ecosystems and climate feedback.


Assuntos
Biomassa , Ecossistema , Pergelissolo , Tibet , Áreas Alagadas , Plantas/metabolismo , Mudança Climática , Temperatura , Ciclo do Carbono , Desenvolvimento Vegetal/fisiologia , Solo/química , Pradaria
3.
Development ; 148(7)2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33688075

RESUMO

An important strategy for establishing mechanisms of gene function during development is through mutation of individual genes and analysis of subsequent effects on cell behavior. Here, we present a single-plasmid approach for genome editing in chick embryos to study experimentally perturbed cells in an otherwise normal embryonic environment. To achieve this, we have engineered a plasmid that encodes Cas9 protein, gene-specific guide RNA (gRNA), and a fluorescent marker within the same construct. Using transfection- and electroporation-based approaches, we show that this construct can be used to perturb gene function in early embryos as well as human cell lines. Importantly, insertion of this cistronic construct into replication-incompetent avian retroviruses allowed us to couple gene knockouts with long-term lineage analysis. We demonstrate the application of our newly engineered constructs and viruses by perturbing ß-catenin in vitro and Sox10, Pax6 and Pax7 in the neural crest, retina, and neural tube and segmental plate in vivo, respectively. Together, this approach enables genes of interest to be knocked out in identifiable cells in living embryos and can be broadly applied to numerous genes in different embryonic tissues.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes/métodos , Plasmídeos/genética , Animais , Embrião de Galinha , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Inativação de Genes/métodos , Crista Neural/metabolismo , Fator de Transcrição PAX6/genética , Fator de Transcrição PAX7 , RNA Guia de Cinetoplastídeos/genética , Fatores de Transcrição SOXE/genética
4.
Eur J Haematol ; 112(5): 776-787, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38226781

RESUMO

BACKGROUND: Essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (MF) are myeloproliferative neoplasms (MPN). Inflammation is involved in the initiation, progression, and symptomology of the diseases. The gut microbiota impacts the immune system, infection control, and steady-state hematopoiesis. METHODS: We analyzed the gut microbiota of 227 MPN patients and healthy controls (HCs) using next-generation sequencing. We expanded our previous results in PV and ET patients with additional PV, pre-MF, and MF patients which allowed us to compare MPN patients collectively, MPN sub-diagnoses, and MPN mutations (separately and combined) vs. HCs (N = 42) and compare within MPN sub-diagnoses and MPN mutation. RESULTS: MPN patients had a higher observed richness (median, 245 [range, 49-659]) compared with HCs (191.5 [range, 111-300; p = .003]) and a lower relative abundance of taxa within the Firmicutes phylum; for example, Faecalibacterium (6% vs. 14%, p < .001). The microbiota of CALR-positive patients (N = 30) resembled that of HCs more than that of patients with JAK2V617F (N = 177). In JAK2V617F-positive patients, only minor differences in the gut microbiota were observed between MPN sub-diagnoses, illustrating the importance of this mutation. CONCLUSION: The gut microbiota in MPN patients differs from HCs and is driven by JAK2V617F, whereas the gut microbiota in CALR patients resembles HCs more.


Assuntos
Microbioma Gastrointestinal , Transtornos Mieloproliferativos , Policitemia Vera , Trombocitemia Essencial , Humanos , Calreticulina/genética , Janus Quinase 2/genética , Transtornos Mieloproliferativos/etiologia , Transtornos Mieloproliferativos/genética , Policitemia Vera/genética , Mutação , Trombocitemia Essencial/genética
5.
Anesth Analg ; 138(6): 1242-1248, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38180886

RESUMO

BACKGROUND: Perioperative treatment of hypotension by intravenous administration of norepinephrine in a peripheral vein can lead to adverse events, for example, tissue necrosis. However, the incidence and severity of adverse events during perioperative administration are unknown. METHODS: This was a prospective observational study conducted at 3 Swedish hospitals from 2019 to 2022. A total of 1004 patients undergoing surgery, who met the criteria for perioperative peripheral norepinephrine administration, were included. The infusion site was inspected regularly. If swelling or paleness of skin was detected, the infusion site was changed to a different peripheral line. Systolic blood pressure and pulse frequency were monitored during the infusion time and defined as adverse events at >220 mm Hg and <40 beats•min -1 . In case of adverse events, patients were observed for up to 48 hours. The primary outcome was prevalence of extravasation, defined as swelling around the infusion site. Secondary outcomes were all types of adverse events and associations between predefined clinical variables and risk of adverse events. RESULTS: We observed 2.3% (95% confidence interval [CI], 1.4%-3.2%) extravasation of infusion and 0.9% (95% CI, 0.4%-1.7%) bradycardia. No cases of tissue necrosis or severe hypertension were detected. All adverse events had dissipated spontaneously within 48 hours. Proximal catheter placement was associated with more adverse events. CONCLUSIONS: Extravasation of peripherally administrated norepinephrine in the perioperative period occurred at similar rates as in previous studies in critically ill patients. In our setting, where we regularly inspected the infusion site and shifted site in case of swelling or paleness of skin, we observed no case of severe adverse events. Given that severe adverse events were absent, the potential benefit of this preventive approach requires confirmation in a larger population.


Assuntos
Norepinefrina , Vasoconstritores , Humanos , Norepinefrina/administração & dosagem , Norepinefrina/efeitos adversos , Estudos Prospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Vasoconstritores/administração & dosagem , Vasoconstritores/efeitos adversos , Suécia/epidemiologia , Infusões Intravenosas , Hipotensão/induzido quimicamente , Hipotensão/diagnóstico , Hipotensão/epidemiologia , Cateterismo Periférico/efeitos adversos , Adulto , Fatores de Risco
6.
Mycoses ; 67(7): e13760, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38943042

RESUMO

BACKGROUND: Microsporum audouinii has resurged recently. Infections with the dermatophyte are difficult to treat, which raises the question if we treat M. audouinii infections with the most effective antifungal (AF) agent. OBJECTIVES: The aims of this study was to investigate an outbreak of tinea capitis (TC) in Denmark, address the challenges in outbreak management and to conduct two reviews regarding previous outbreaks and minimal inhibitory concentration (MIC). METHODS: We used Wood's light, culture, direct microscopy, and PCR for screening and antifungal susceptibility testing (AFST) for treatment optimization. We performed two reviews to explore M. audouinii outbreaks and MIC values using broth microdilution method. RESULTS: Of 73 screened individuals, 10 had confirmed M. audouinii infections. Clinical resistance to griseofulvin was observed in 4 (66%) cases. While previous outbreaks showed high griseofulvin efficacy, our study favoured terbinafine, fluconazole and itraconazole in our hard-to-treat cases. AFST guided the choice of AF. Through the literature search, we identified five M. audouinii outbreaks, where differences in management included the use of Wood's light and prophylactic topical AF therapy. Terbinafine MIC values from the literature ranged from 0.002 to 0.125 mg/L. CONCLUSION: Use of Wood's light and preventive measurements were important for limiting infection. The literature lacked MIC data for griseofulvin against M. audouinii, but indicated sensitivity for terbinafine. The clinical efficacy for M. audouinii treatment was contradictory favouring both terbinafine and griseofulvin. AFST could have a key role in the treatment of difficult cases, but lack of standardisation of AFST and MIC breakpoints limits its usefulness.


Assuntos
Antifúngicos , Surtos de Doenças , Farmacorresistência Fúngica , Testes de Sensibilidade Microbiana , Microsporum , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Humanos , Microsporum/efeitos dos fármacos , Masculino , Feminino , Dinamarca/epidemiologia , Adulto , Criança , Terbinafina/farmacologia , Terbinafina/uso terapêutico , Pessoa de Meia-Idade , Tinha do Couro Cabeludo/tratamento farmacológico , Tinha do Couro Cabeludo/microbiologia , Tinha do Couro Cabeludo/epidemiologia , Griseofulvina/farmacologia , Griseofulvina/uso terapêutico , Pré-Escolar , Adolescente , Adulto Jovem , Tinha/tratamento farmacológico , Tinha/microbiologia , Tinha/epidemiologia , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Idoso , Fluconazol/farmacologia , Fluconazol/uso terapêutico
7.
Clin Infect Dis ; 77(2): 242-251, 2023 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-36947131

RESUMO

BACKGROUND: In the POET (Partial Oral Endocarditis Treatment) trial, oral step-down therapy was noninferior to full-length intravenous antibiotic administration. The aim of the present study was to perform pharmacokinetic/pharmacodynamic analyses for oral treatments of infective endocarditis to assess the probabilities of target attainment (PTAs). METHODS: Plasma concentrations of oral antibiotics were measured at day 1 and 5. Minimal inhibitory concentrations (MICs) were determined for the bacteria causing infective endocarditis (streptococci, staphylococci, or enterococci). Pharmacokinetic/pharmacodynamic targets were predefined according to literature using time above MIC or the ratio of area under the curve to MIC. Population pharmacokinetic modeling and pharmacokinetic/pharmacodynamic analyses were done for amoxicillin, dicloxacillin, linezolid, moxifloxacin, and rifampicin, and PTAs were calculated. RESULTS: A total of 236 patients participated in this POET substudy. For amoxicillin and linezolid, the PTAs were 88%-100%. For moxifloxacin and rifampicin, the PTAs were 71%-100%. Using a clinical breakpoint for staphylococci, the PTAs for dicloxacillin were 9%-17%.Seventy-four patients at day 1 and 65 patients at day 5 had available pharmacokinetic and MIC data for 2 oral antibiotics. Of those, 13 patients at day 1 and 14 patients at day 5 did only reach the target for 1 antibiotic. One patient did not reach target for any of the 2 antibiotics. CONCLUSIONS: For the individual orally administered antibiotic, the majority reached the target level. Patients with sub-target levels were compensated by the administration of 2 different antibiotics. The findings support the efficacy of oral step-down antibiotic treatment in patients with infective endocarditis.


Assuntos
Endocardite Bacteriana , Endocardite , Humanos , Rifampina/uso terapêutico , Dicloxacilina/uso terapêutico , Linezolida/uso terapêutico , Moxifloxacina/uso terapêutico , Antibacterianos/farmacologia , Endocardite/tratamento farmacológico , Endocardite Bacteriana/tratamento farmacológico , Endocardite Bacteriana/microbiologia , Amoxicilina , Testes de Sensibilidade Microbiana
8.
J Antimicrob Chemother ; 78(12): 2840-2848, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37823408

RESUMO

BACKGROUND: Linezolid in combination with rifampicin has been used in treatment of infective endocarditis especially for patients infected with staphylococci. OBJECTIVES: Because rifampicin has been reported to reduce the plasma concentration of linezolid, the present study aimed to characterize the population pharmacokinetics of linezolid for the purpose of quantifying an effect of rifampicin cotreatment. In addition, the possibility of compensation by dosage adjustments was evaluated. PATIENTS AND METHODS: Pharmacokinetic measurements were performed in 62 patients treated with linezolid for left-sided infective endocarditis in the Partial Oral Endocarditis Treatment (POET) trial. Fifteen patients were cotreated with rifampicin. A total of 437 linezolid plasma concentrations were obtained. The pharmacokinetic data were adequately described by a one-compartment model with first-order absorption and first-order elimination. RESULTS: We demonstrated a substantial increase of linezolid clearance by 150% (95% CI: 78%-251%), when combined with rifampicin. The final model was evaluated by goodness-of-fit plots showing an acceptable fit, and a visual predictive check validated the model. Model-based dosing simulations showed that rifampicin cotreatment decreased the PTA of linezolid from 94.3% to 34.9% and from 52.7% to 3.5% for MICs of 2 mg/L and 4 mg/L, respectively. CONCLUSIONS: A substantial interaction between linezolid and rifampicin was detected in patients with infective endocarditis, and the interaction was stronger than previously reported. Model-based simulations showed that increasing the linezolid dose might compensate without increasing the risk of adverse effects to the same degree.


Assuntos
Endocardite Bacteriana , Rifampina , Humanos , Linezolida , Rifampina/uso terapêutico , Rifampina/farmacocinética , Antibacterianos , Endocardite Bacteriana/tratamento farmacológico , Mitomicina/uso terapêutico
9.
Microb Pathog ; 182: 106236, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37419218

RESUMO

Salmonella enterica serovar Gallinarum causes Fowl Typhoid in poultry, and it is host specific to avian species. The reasons why S. Gallinarum is restricted to avians, and at the same time predominately cause systemic infections in these hosts, are unknown. In the current study, we developed a surgical approach to study gene expression inside the peritoneal cavity of hens to shed light on this. Strains of the host specific S. Gallinarum, the cattle-adapted S. Dublin and the broad host range serovar, S. Enteritidis, were enclosed in semi-permeable tubes and surgically placed for 4 h in the peritoneal cavity of hens and for control in a minimal medium at 41.2 °C. Global gene-expression under these conditions was compared between serovars using tiled-micro arrays with probes representing the genome of S. Typhimurium, S. Dublin and S. Gallinarum. Among other genes, genes of SPI-13, SPI-14 and the macrophage survival gene mig-14 were specifically up-regulated in the host specific serovar, S. Gallinarum, and further studies into the role of these genes in host specific infection are highly indicated. Analysis of pathways and GO-terms, which were enriched in the host specific S. Gallinarum without being enriched in the two other serovars indicated that host specificity was characterized by a metabolic fine-tuning as well as unique expression of virulence associated pathways. The cattle adapted serovar S. Dublin differed from the two other serovars by a lack of up-regulation of genes encoded in the virulence associated pathogenicity island 2, and this may explain the inability of this serovar to cause disease in poultry.


Assuntos
Salmonelose Animal , Salmonella enterica , Animais , Feminino , Bovinos , Sorogrupo , Galinhas , Transcriptoma , Salmonella enterica/genética , Salmonella enteritidis/genética
10.
Artigo em Inglês | MEDLINE | ID: mdl-37755156

RESUMO

Average nucleotide identity analysis, based on whole genome sequences of 115 strains previously identified as Aerococcus urinae, an emerging uropathogen, discriminates at least six unique genomic taxa. The whole genome analysis affords clearer species boundaries over 16S rRNA gene sequencing and traditional phenotypic approaches for the identification and phylogenetic organization of Aerococcus species. The newly described species can be differentiated by matrix-assisted laser desorption ionization time-of-flight analysis of protein signatures. We propose the emendation of the description of A. urinae (type strain ATCC 51268T = CCUG 34223T=NCFB 2893) and the names of Aerococcus tenax sp. nov. (ATCC TSD-302T = DSM 115700T = CCUG 76531T=NR-58630T), Aerococcus mictus sp. nov. (ATCC TSD-301T = DSM 115699T = CCUG 76532T=NR-58629T), and Aerococcus loyolae sp. nov. (ATCC TSD-300T = DSM 115698T = CCUG 76533T=NR-58628T) for three of the newly identified genomic taxa.


Assuntos
Aerococcus , Aerococcus/genética , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Composição de Bases , Ácidos Graxos/química
11.
N Engl J Med ; 380(5): 415-424, 2019 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-30152252

RESUMO

BACKGROUND: Patients with infective endocarditis on the left side of the heart are typically treated with intravenous antibiotic agents for up to 6 weeks. Whether a shift from intravenous to oral antibiotics once the patient is in stable condition would result in efficacy and safety similar to those with continued intravenous treatment is unknown. METHODS: In a randomized, noninferiority, multicenter trial, we assigned 400 adults in stable condition who had endocarditis on the left side of the heart caused by streptococcus, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci and who were being treated with intravenous antibiotics to continue intravenous treatment (199 patients) or to switch to oral antibiotic treatment (201 patients). In all patients, antibiotic treatment was administered intravenously for at least 10 days. If feasible, patients in the orally treated group were discharged to outpatient treatment. The primary outcome was a composite of all-cause mortality, unplanned cardiac surgery, embolic events, or relapse of bacteremia with the primary pathogen, from the time of randomization until 6 months after antibiotic treatment was completed. RESULTS: After randomization, antibiotic treatment was completed after a median of 19 days (interquartile range, 14 to 25) in the intravenously treated group and 17 days (interquartile range, 14 to 25) in the orally treated group (P=0.48). The primary composite outcome occurred in 24 patients (12.1%) in the intravenously treated group and in 18 (9.0%) in the orally treated group (between-group difference, 3.1 percentage points; 95% confidence interval, -3.4 to 9.6; P=0.40), which met noninferiority criteria. CONCLUSIONS: In patients with endocarditis on the left side of the heart who were in stable condition, changing to oral antibiotic treatment was noninferior to continued intravenous antibiotic treatment. (Funded by the Danish Heart Foundation and others; POET ClinicalTrials.gov number, NCT01375257 .).


Assuntos
Administração Oral , Antibacterianos/administração & dosagem , Endocardite Bacteriana/tratamento farmacológico , Administração Intravenosa , Idoso , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Bacteriemia/tratamento farmacológico , Endocardite Bacteriana/microbiologia , Endocardite Bacteriana/mortalidade , Feminino , Próteses Valvulares Cardíacas/microbiologia , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Recidiva
12.
PLoS Biol ; 17(10): e3000392, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31613872

RESUMO

2018: Arctic researchers have just witnessed another extreme summer-but in a new sense of the word. Although public interest has long been focused on general warming trends and trends towards a lower sea ice cover in the Arctic Ocean, this summer saw the realization of another predicted trend: that of increasing precipitation during the winter months and of increased year-to-year variability. In a well-studied ecosystem in Northeast Greenland, this resulted in the most complete reproductive failure encountered in the terrestrial ecosystem during more than two decades of monitoring: only a few animals and plants were able to reproduce because of abundant and late melting snow. These observations, we suggest, should open our eyes to potentially drastic consequences of predicted changes in both the mean and the variability of arctic climate.


Assuntos
Aves/fisiologia , Mudança Climática , Aptidão Genética , Mamíferos/fisiologia , Dormência de Plantas , Animais , Regiões Árticas , Ecossistema , Plantas , Chuva , Estações do Ano
13.
Qual Life Res ; 31(9): 2655-2662, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35349038

RESUMO

PURPOSE: Self-assessed poor health status is associated with increased risk of mortality in several cardiovascular conditions, but has not been investigated in patients with endocarditis. We examined health status and mortality in patients with endocarditis. METHODS: This is a re-specified substudy of the randomized POET endocarditis trial, which included 400 patients. Patients completed the single-question self-assessed health status from the Short-Form 36 questionnaire at time of randomization and were categorized as having poor or non-poor (excellent/very good, good, or fair) health status. Self-assessed health status and all-cause mortality were examined by a Cox regression model. RESULTS: Self-assessed health status was completed by 266 (67%) patients with a mean age of 68.0 years (± 11.8), 54 (20%) were females, and 86 (32%) had one or more major concurrent medical conditions besides endocarditis. The self-assessed health status distribution was poor (n = 21, 8%) and non-poor (n = 245, 92%). The median follow-up was 3.3 years and death occurred in 9 (43%) and 48 (20%) patients reporting poor and non-poor health status, respectively, and mortality rates [mortality/100 person-years, 95% confidence interval (CI)] were 18.1 (95% CI 9.4-34.8) and 5.4 (95% CI 4.1-7.2), i.e., the crude hazard ratio for death was 3.4 (95% CI: 1.7-7.0, p < 0.01). CONCLUSION: Self-assessed poor health status compared with non-poor health status as assessed by a single question was associated with a threefold increased long-term mortality in patients with endocarditis. POET ClinicalTrials.gov number, NCT01375257. TRIAL REGISTRY: POET ClinicalTrials.gov number, NCT01375257.


Assuntos
Endocardite , Qualidade de Vida , Idoso , Feminino , Nível de Saúde , Humanos , Masculino , Modelos de Riscos Proporcionais , Qualidade de Vida/psicologia , Inquéritos e Questionários
14.
Acta Anaesthesiol Scand ; 66(5): 606-614, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35122232

RESUMO

BACKGROUND: The prevalence and importance of cardiac dysfunction in critically ill patients with COVID-19 in Sweden is not yet established. The aim of the study was to assess the prevalence of cardiac dysfunction and elevated pulmonary artery pressure (PAP), and its influence on mortality in patients with COVID-19 in intensive care in Sweden. METHODS: This was a multicentre observational study performed in five intensive care units (ICUs) in Sweden. Patients admitted to participating ICU with COVID-19 were examined with echocardiography within 72 h from admission and again after 4 to 7 days. Cardiac dysfunction was defined as left ventricular (LV) dysfunction (ejection fraction <50% and/or regional hypokinesia) or right ventricular (RV) dysfunction (defined as TAPSE <17 mm or visually assessed moderate/severe RV dysfunction). RESULTS: We included 132 patients, of whom 127 (96%) were intubated. Cardiac dysfunction was found in 42 (32%) patients. Most patients had cardiac dysfunction at the first assessment (n = 35) while a few developed cardiac dysfunction later (n = 7) and some changed type of dysfunction (n = 3). LV dysfunction was found in 21 and RV dysfunction in 19 patients, while 5 patients had combined dysfunction. Elevated PAP was found in 34 patients (26%) and was more common in patients with RV dysfunction. RV dysfunction and elevated PAP were independently associated with an increased risk of death (OR 3.98, p = .013 and OR 3.88, p = .007, respectively). CONCLUSIONS: Cardiac dysfunction occurs commonly in critically ill patients with COVID-19 in Sweden. RV dysfunction and elevated PAP are associated with an increased risk of death.


Assuntos
COVID-19 , Cardiopatias , Disfunção Ventricular Esquerda , Disfunção Ventricular Direita , COVID-19/complicações , Estado Terminal , Cardiopatias/complicações , Humanos , Suécia/epidemiologia
15.
Proc Natl Acad Sci U S A ; 116(48): 23942-23946, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31712413

RESUMO

Hurricanes are the most destructive natural disasters in the United States. The record of economic damage from hurricanes shows a steep positive trend dominated by increases in wealth. It is necessary to account for temporal changes in exposed wealth, in a process called normalization, before we can compare the destructiveness of recorded damaging storms from different areas and at different times. Atmospheric models predict major hurricanes to get more intense as Earth warms, and we expect this trend to eventually emerge above the natural variability in the record of normalized damage. However, the evidence for an increasing trend in normalized damage since 1900 has been controversial. In this study, we develop a record of normalized damage since 1900 based on an equivalent area of total destruction. Here, we show that this record has an improved signal-to-noise ratio over earlier normalization schemes based on calculations of present-day economic damage. Our data reveal an emergent positive trend in damage, which we attribute to a detectable change in extreme storms due to global warming. Moreover, we show that this increasing trend in damage can also be exposed in existing normalized damage records by looking at the frequency of the largest damage events. Our record of normalized damage, framed in terms of an equivalent area of total destruction, is a more reliable measure for climate-related changes in extreme weather, and can be used for better risk assessments on hurricane disasters.

16.
J Clin Microbiol ; 59(2)2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33208473

RESUMO

A correct identification of Streptococcus pseudopneumoniae is a prerequisite for investigating the clinical impact of the bacterium. The identification has traditionally relied on phenotypic methods. However, these phenotypic traits have been shown to be unreliable, with some S. pseudopneumoniae strains giving conflicting results. Therefore, sequence-based identification methods have increasingly been used for identification of S. pseudopneumoniae In this study, we used 64 S. pseudopneumoniae strains, 59 S. pneumoniae strains, 22 S. mitis strains, 24 S. oralis strains, 6 S. infantis strains, and 1 S. peroris strain to test the capability of three single genes (rpoB, gyrB, and recA), two multilocus sequence analysis (MLSA) schemes, the single nucleotide polymorphism (SNP)-based phylogeny tool CSI phylogeny, a k-mer-based identification method (KmerFinder), average nucleotide identity (ANI) using fastANI, and core genome analysis to identify S. pseudopneumoniae Core genome analysis and CSI phylogeny were able to cluster all strains into distinct clusters related to their respective species. It was not possible to identify all S. pseudopneumoniae strains correctly using only one of the single genes. The MLSA schemes were unable to identify some of the S. pseudopneumoniae strains, which could be misidentified. KmerFinder identified all S. pseudopneumoniae strains but misidentified one S. mitis strain as S. pseudopneumoniae, and fastANI differentiated between S. pseudopneumoniae and S. pneumoniae using an ANI cutoff of 96%.


Assuntos
Streptococcus pneumoniae , Streptococcus , Genoma Bacteriano/genética , Filogenia , Análise de Sequência de DNA , Streptococcus/genética , Streptococcus pneumoniae/genética
19.
J Antimicrob Chemother ; 75(7): 1671-1680, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32240295

RESUMO

BACKGROUND: Among the measures taken to preserve the clinical efficacy of highest priority critically important antimicrobials (HP-CIAs), the WHO has recommended avoiding their use in food-producing animals. Little is known regarding the indications for which different antimicrobial classes are used in animals, even in countries where data on antimicrobial use are available. OBJECTIVES: To outline, in a narrative review, the diseases for which HP-CIAs are used in veterinary medicine, highlighting incongruences with international guidelines and disease conditions where effective alternatives to HP-CIAs are missing. METHODS: Scientific literature, national reports and expert opinion were used to describe the indications for the use of HP-CIAs in the main food-producing (pigs, cattle and poultry) and companion (horses, dogs and cats) animal species. RESULTS: The most common indications for use of HP-CIAs are enteric and respiratory infections in pigs, cattle and poultry, urogenital infections in dogs and cats and respiratory infections in horses. In some instances, no valid and convenient alternatives to colistin and macrolides are available against certain porcine enteric and bovine respiratory pathogens. Effective, legal and convenient alternatives to HP-CIAs are also lacking for managing common infections in cats, for which oral administration is difficult, Rhodococcus equi infections in horses, some enteric and respiratory infections in poultry and MDR infections in all companion animal species. CONCLUSIONS: Future research and stewardship programmes should focus on the disease conditions identified by this review to reduce the use of HP-CIAs in the veterinary sector.


Assuntos
Anti-Infecciosos , Doenças do Gato , Doenças do Cão , Animais , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Gatos , Bovinos , Doenças do Cão/tratamento farmacológico , Cães , Cavalos , Macrolídeos , Suínos
20.
BMC Vet Res ; 16(1): 148, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32434525

RESUMO

BACKGROUND: Infection in the oviduct (salpingitis) is the most common bacterial infection in egg laying hens and is mainly caused by Escherichia coli. The disease is responsible for decreased animal welfare, considerable economic loss as well as a risk of horizontal and vertical transmission of pathogenic E. coli. The outcome of salpingitis may be either acute or chronic. It has not yet been clarified whether the pathological manifestation is a result of the characteristics of the E. coli or whether the manifestation is associated with host factors such as host immunity. RESULTS: From the core- and accessory genome analysis and comparison of 62 E. coli no genetic markers were found to be associated to either acute or chronic infection. Twenty of the 62 genomes harboured at least one antimicrobial resistance gene with resistance against sulfonamides being the most common. The increased serum survival and iron chelating genes iss and iroN were highly prevalent in genomes from both acute and chronic salpingitis. CONCLUSION: Our analysis revealed that no genetic markers could differentiate the E. coli isolated from acute versus chronic salpingitis in egg laying hens. The difference in pathological outcome may be related to other factors such as immunological status, genetics and health of the host. These data indicate that salpingitis is another manifestation of colibacillosis.


Assuntos
Infecções por Escherichia coli/veterinária , Escherichia coli/genética , Doenças das Aves Domésticas/microbiologia , Salpingite/veterinária , Animais , Galinhas , Farmacorresistência Bacteriana/genética , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Feminino , Genoma Bacteriano , Doenças das Aves Domésticas/patologia , Salpingite/microbiologia , Salpingite/patologia , Sequenciamento Completo do Genoma
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