RESUMO
Influenza A/H9 viruses circulate worldwide in wild and domestic avian species, continuing to evolve and posing a zoonotic risk. A substantial increase in human infections with A/H9N2 subtype avian influenza viruses (AIVs) and the emergence of novel reassortants carrying A/H9N2-origin internal genes has occurred in recent years. Different names have been used to describe the circulating and emerging A/H9 lineages. To address this issue, an international group of experts from animal and public health laboratories, endorsed by the WOAH/FAO Network of Expertise on Animal Influenza, has created a practical lineage classification and nomenclature system based on the analysis of 10,638 hemagglutinin sequences from A/H9 AIVs sampled worldwide. This system incorporates phylogenetic relationships and epidemiologic characteristics designed to trace emerging and circulating lineages and clades. To aid in lineage and clade assignment, an online tool has been created. This proposed classification enables rapid comprehension of the global spread and evolution of A/H9 AIVs.
Assuntos
Influenza Aviária , Influenza Humana , Filogenia , Terminologia como Assunto , Animais , Humanos , Influenza Humana/epidemiologia , Influenza Humana/virologia , Influenza Aviária/virologia , Influenza Aviária/epidemiologia , Aves/virologia , Vírus da Influenza A Subtipo H9N2/genética , Vírus da Influenza A Subtipo H9N2/classificação , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genéticaRESUMO
G protein-coupled receptors (GPCRs) exist within a landscape of interconvertible conformational states and in dynamic equilibrium between monomers and higher-order oligomers, both influenced by ligand binding. Here, we show that a homobivalent ligand formed by equal chromenopyrazole moieties as pharmacophores, connected by 14 methylene units, can modulate the dynamics of the cannabinoid CB2 receptor (CB2R) homodimerization by simultaneously binding both protomers of the CB2R-CB2R homodimer. Computational and pharmacological experiments showed that one of the ligand pharmacophores binds to the orthosteric site of one protomer, and the other pharmacophore to a membrane-oriented pocket between transmembranes 1 and 7 of the partner protomer. This results in unique pharmacological properties, including increased potency in Gi-mediated signaling and enhanced recruitment of ß-arrestin. Thus, by modulating dimerization dynamics, it may be possible to fine-tune CB2R activity, potentially leading to improved therapeutic outcomes.
Assuntos
Multimerização Proteica , Receptor CB2 de Canabinoide , Transdução de Sinais , Receptor CB2 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/química , Ligantes , Humanos , Transdução de Sinais/efeitos dos fármacos , Multimerização Proteica/efeitos dos fármacos , Células HEK293 , Pirazóis/farmacologia , Pirazóis/química , Animais , beta-Arrestinas/metabolismoRESUMO
Psychedelics have emerged as promising therapeutics for several psychiatric disorders. Hypotheses around their mechanisms have revolved around their partial agonism at the serotonin 2â¯A receptor, leading to enhanced neuroplasticity and brain connectivity changes that underlie positive mindset shifts. However, these accounts fail to recognise that the gut microbiota, acting via the gut-brain axis, may also have a role in mediating the positive effects of psychedelics on behaviour. In this review, we present existing evidence that the composition of the gut microbiota may be responsive to psychedelic drugs, and in turn, that the effect of psychedelics could be modulated by microbial metabolism. We discuss various alternative mechanistic models and emphasize the importance of incorporating hypotheses that address the contributions of the microbiome in future research. Awareness of the microbial contribution to psychedelic action has the potential to significantly shape clinical practice, for example, by allowing personalised psychedelic therapies based on the heterogeneity of the gut microbiota.
Assuntos
Eixo Encéfalo-Intestino , Microbioma Gastrointestinal , Alucinógenos , Alucinógenos/farmacologia , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Eixo Encéfalo-Intestino/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismoRESUMO
The present study examined three hallucinogenic amphetamine derivatives, namely, 2,5-dimethoxy-4-iodoamphetamine (DOI) as well as 2,5-dimethoxy-4-methylamphetamine (DOM) and 4-methylmethcathinone (mephedrone). The objective of this study was to test the hypothesis that DOI, DOM, and mephedrone would increase the contractile force in isolated human atrial preparations in a manner similar to amphetamine. To this end, we measured contractile force under isometric conditions in electrically stimulated (1 Hz) human atrial preparations obtained during open surgery. DOI and DOM alone or in the presence of isoprenaline reduced the contractile force concentration-dependently in human atrial preparations. These negative inotropic effects of DOM and DOI were not attenuated by 10 µM atropine. However, mephedrone increased the contractile force in human atrial preparations in a concentration- and time-dependent manner. Furthermore, these effects were attenuated by the subsequent addition of 10 µM propranolol or pretreatment with 10 µM cocaine in the organ bath. Therefore, it can be concluded that amphetamine derivatives may exert opposing effects on cardiac contractile force. The precise mechanism by which DOI and DOM exert their negative inotropic effects remains unknown at present. The cardiac effects of mephedrone are probably due to the release of cardiac noradrenaline.
Assuntos
Alucinógenos , Átrios do Coração , Contração Miocárdica , Humanos , Átrios do Coração/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Alucinógenos/farmacologia , Masculino , Feminino , Isoproterenol/farmacologia , Metanfetamina/farmacologia , Metanfetamina/análogos & derivados , Atropina/farmacologia , Anfetaminas/farmacologia , Pessoa de Meia-Idade , Propranolol/farmacologia , Anfetamina/farmacologia , AdultoRESUMO
Dengue, a mosquitoborne flavivirus infection, is increasingly a disease of older adults who are more likely to have chronic diseases that confer risk for severe outcomes of dengue infection. In a population-based study in Taiwan, adjusted risks for dengue-related hospitalization, intensive care unit admission, and death increased progressively with age.
Assuntos
Dengue , Hospitalização , Humanos , Idoso , Taiwan , Unidades de Terapia IntensivaRESUMO
Meningitis caused by Cryptococcus tetragattii fungus is rare and has been found in specific geographic regions. We report a case of meningitis caused by C. tetragattii (molecular type VGIV) in an immunocompetent patient in Taiwan. The patient had traveled to Egypt and was positive for granulocyte-macrophage colony-stimulating factor autoantibody.
Assuntos
Cryptococcus , Meningite Criptocócica , Meningite , Humanos , Taiwan , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/tratamento farmacológico , FungosRESUMO
Antimicrobial resistance is a major threat to human health. Since the 2000s, computational tools for predicting infectious diseases have been greatly advanced; however, efforts to develop real-time forecasting models for antimicrobial-resistant organisms (AMROs) have been absent. In this perspective, we discuss the utility of AMRO forecasting at different scales, highlight the challenges in this field, and suggest future research priorities. We also discuss challenges in scientific understanding, access to high-quality data, model calibration, and implementation and evaluation of forecasting models. We further highlight the need to initiate research on AMRO forecasting using currently available data and resources to galvanize the research community and address initial practical questions.
Assuntos
Antibacterianos , Doenças Transmissíveis , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Previsões , Confiabilidade dos DadosRESUMO
We report a rare case of aorto-bi-iliac prosthetic allograft mucormycosis in a 57-year-old immunocompetent patient in France. Outcome was favorable after surgery and dual antifungal therapy with liposomal amphotericin B and isavuconazole. In a literature review, we identified 12 other cases of prosthetic vascular or heart valve mucormycosis; mortality rate was 38%.
Assuntos
Mucormicose , Humanos , Pessoa de Meia-Idade , Mucormicose/diagnóstico , Mucormicose/tratamento farmacológico , Mucormicose/microbiologia , Antifúngicos/uso terapêutico , Rhizopus , Transplante Homólogo , PulmãoRESUMO
We report a 34-year-old man who had a nonhealing, verrucous plaque with central ulceration on the lower leg. This case-patient is a rare example of endemic limited cutaneous leishmaniasis in Tucson, Arizona, USA. Clinicians should be aware of this disease because its manifestations can vary for individual patients.
Assuntos
Leishmaniose Cutânea , Leishmaniose , Masculino , Humanos , Adulto , Perna (Membro) , Arizona/epidemiologia , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/epidemiologiaRESUMO
We identified 2 fatal cases of persons infected with hantavirus in Arizona, USA, 2020; 1 person was co-infected with SARS-CoV-2. Delayed identification of the cause of death led to a public health investigation that lasted ≈9 months after their deaths, which complicated the identification of a vector or exposure.
Assuntos
COVID-19 , Doenças Transmissíveis , Infecções por Hantavirus , Orthohantavírus , Humanos , Arizona/epidemiologia , SARS-CoV-2 , Pandemias , Infecções por Hantavirus/diagnóstico , Infecções por Hantavirus/epidemiologiaRESUMO
The Omicron variant of SARS-CoV-2 has become dominant in most countries and has raised significant global health concerns. As a global commerce center, New York, New York, USA, constantly faces the risk for multiple variant introductions of SARS-CoV-2. To elucidate the introduction and transmission of the Omicron variant in the city of New York, we created a comprehensive genomic and epidemiologic analysis of 392 Omicron virus specimens collected during November 25-December 11, 2021. We found evidence of 4 independent introductions of Omicron subclades, including the Omicron subclade BA.1.1 with defining substitution of R346K in the spike protein. The continuous genetic divergence within each Omicron subclade revealed their local community transmission and co-circulation in New York, including both household and workplace transmissions supported by epidemiologic evidence. Our study highlights the urgent need for enhanced genomic surveillance and effective response planning for better prevention and management of emerging SARS-CoV-2 variants.
Assuntos
COVID-19 , Humanos , New York/epidemiologia , COVID-19/epidemiologia , SARS-CoV-2/genética , ComércioRESUMO
We examined armadillos from museum collections in the United States using molecular assays to detect leprosy-causing bacilli. We found Mycobacterium leprae bacilli in samples from the United States, Bolivia, and Paraguay; prevalence was 14.8% in nine-banded armadillos. US isolates belonged to subtype 3I-2, suggesting long-term circulation of this genotype.
Assuntos
Hanseníase , Mycobacterium leprae , Humanos , Estados Unidos , Animais , Tatus/microbiologia , Hanseníase/microbiologia , Museus , GenótipoRESUMO
Inquilinus limosus is an environmental bacterium associated with respiratory tract colonization in cystic fibrosis patients. We report a case of I. limosus bacteremia in a patient in France who received a lung transplant and experienced chronic graft dysfunction and SARS-CoV-2 infection. This case suggests I. limosus displays virulence factors associated with invasion.
Assuntos
Bacteriemia , COVID-19 , Humanos , Transplantados , SARS-CoV-2 , PulmãoRESUMO
While investigating the death of a hippopotamus at a zoo in Hanoi, Vietnam, we isolated SARS-CoV-2 and sequenced the RNA-dependent RNA polymerase gene from different organs. Phylogenetic analysis showed that the SARS-CoV-2 strain was closely related to 3 human SARS-CoV-2 strains in Vietnam.
Assuntos
Artiodáctilos , COVID-19 , Animais , Humanos , SARS-CoV-2 , Filogenia , VietnãRESUMO
We describe an unusual outbreak of respiratory infections caused by human metapneumovirus in children during the sixth wave of COVID-19 in Spain, associated with the Omicron variant. Patients in this outbreak were older than usual and showed more hypoxia and pneumonia, longer length of stay, and greater need for intensive care.
Assuntos
COVID-19 , Metapneumovirus , Infecções por Paramyxoviridae , Infecções Respiratórias , Criança , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Espanha/epidemiologia , Pandemias , Infecções por Paramyxoviridae/epidemiologia , Infecções Respiratórias/epidemiologiaRESUMO
A single SARS-CoV-2 vaccine dose reduces onward transmission from case-patients. We assessed the potential effects of receiving 2 doses on household transmission for case-patients in England and their household contacts. We used stratified Cox regression models to calculate hazard ratios (HRs) for contacts becoming secondary case-patients, comparing contacts of 2-dose vaccinated and unvaccinated index case-patients. We controlled for age, sex, and vaccination status of case-patients and contacts, as well as region, household composition, and relative socioeconomic condition based on household location. During the Alpha-dominant period, HRs were 0.19 (0.13-0.28) for contacts of 2-dose BNT162b2-vaccinated case-patients and 0.54 (0.41-0.69) for contacts of 2-dose Ch4dOx1-vaccinated case-patients; during the Delta-dominant period, HRs were higher, 0.74 (0.72-0.76) for BNT162b2 and 1.06 (1.04-1.08) for Ch4dOx1. Reduction of onward transmission was lower for index case-patients who tested positive ≥2 months after the second dose of either vaccine.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , Vacina BNT162 , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinação , Inglaterra/epidemiologiaRESUMO
Africa's Lake Tanganyika basin is a cholera hotspot. During 2001-2020, Vibrio cholerae O1 isolates obtained from the Democratic Republic of the Congo side of the lake belonged to 2 of the 5 clades of the AFR10 sublineage. One clade became predominant after acquiring a parC mutation that decreased susceptibility to ciprofloxacin.
Assuntos
Cólera , Vibrio cholerae O1 , Humanos , Vibrio cholerae O1/genética , Tanzânia , Lagos , Cólera/epidemiologia , GenômicaRESUMO
Cetacean morbillivirus (CeMV) causes illness and death in cetaceans worldwide; the CeMV strains circulating in the Southern Hemisphere are poorly known. We detected a pilot whale CeMV strain in 3 short-finned pilot whales (Globicephala macrorhynchus) stranded in Brazil during July-October 2020. Our results confirm this virus circulates in this species.
Assuntos
Infecções por Morbillivirus , Morbillivirus , Baleias Piloto , Animais , Infecções por Morbillivirus/diagnóstico , Infecções por Morbillivirus/veterinária , Brasil/epidemiologia , Morbillivirus/genéticaRESUMO
In July 2019, Bourbon virus RNA was detected in an Amblyomma americanum tick removed from a resident of Long Island, New York, USA. Tick infection and white-tailed deer (Odocoileus virginianus) serosurvey results demonstrate active transmission in New York, especially Suffolk County, emphasizing a need for surveillance anywhere A. americanum ticks are reported.
Assuntos
Cervos , Carrapatos , Animais , New York/epidemiologia , Vetores AracnídeosRESUMO
During the SARS-CoV-2 pandemic, few cases of Nocar-dia spp. co-infection have been reported during or after a COVID-19 infection. Nocardia spp. are gram-positive aerobic actinomycetes that stain partially acid-fast, can infect immunocompromised patients, and may cause dis-seminated disease. We report the case of a 52-year-old immunocompromised man who had Nocardia pseudobrasiliensis pneumonia develop after a SARS-CoV-2 in-fection. We also summarize the literature for no-cardiosis and SARS-CoV-2 co-infections. Nocardia spp. infection should remain a part of the differential diagnosis for pneumonia in immunocompromised hosts, regardless of other co-infections. Sulfonamide/carbapenem combina-tions are used as empiric therapy for nocardiosis; species identification and susceptibility testing are required to se-lect the optimal treatment for each patient.