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BACKGROUND: Mineralocorticoid receptor blockade could be a potential approach for the inhibition of chronic kidney disease (CKD) progression. The benefits and harms of different mineralocorticoid receptor antagonists (MRAs) in CKD are inconsistent. OBJECTIVES: The aim of the study was to summarize the benefits and harms of MRAs for CKD patients. METHODS: We searched MEDLINE, EMBASE, and the Cochrane databases for trials assessing the effects of MRAs on non-dialysis-dependent CKD populations. Treatment and adverse effects were summarized using meta-analysis. RESULTS: Fifty-three trials with 6 different MRAs involving 22,792 participants were included. Compared with the control group, MRAs reduced urinary albumin-to-creatinine ratio (weighted mean difference [WMD], -90.90 mg/g, 95% CI, -140.17 to -41.64 mg/g), 24-h urinary protein excretion (WMD, -0.20 g, 95% CI, -0.28 to -0.12 g), estimated glomerular filtration rate (eGFR) (WMD, -1.99 mL/min/1.73 m2, 95% CI, -3.28 to -0.70 mL/min/1.73 m2), chronic renal failure events (RR, 0.86, 95% CI, 0.79-0.93), and cardiovascular events (RR, 0.84, 95% CI, 0.77-0.92). MRAs increased the incidence of hyperkalemia (RR, 2.04, 95% CI, 1.73-2.40) and hypotension (RR, 1.80, 95% CI, 1.41-2.31). MRAs reduced the incidence of peripheral edema (RR, 0.65, 95% CI, 0.56-0.75) but not the risk of acute kidney injury (RR, 0.94, 95% CI, 0.79-1.13). Nonsteroidal MRAs (RR, 0.66, 95% CI, 0.57-0.75) but not steroidal MRAs (RR, 0.20, 95% CI, 0.02-1.68) significantly reduced the risk of peripheral edema. Steroidal MRAs (RR, 5.68, 95% CI, 1.26-25.67) but not nonsteroidal MRAs (RR, 0.52, 95% CI, 0.22-1.22) increased the risk of breast disorders. CONCLUSIONS: In the CKD patients, MRAs, particularly in combination with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, reduced albuminuria/proteinuria, eGFR, and the incidence of chronic renal failure, cardiovascular and peripheral edema events, whereas increasing the incidence of hyperkalemia and hypotension, without the augment of acute kidney injury events. Nonsteroidal MRAs were superior in the reduction of more albuminuria with fewer peripheral edema events and without the augment of breast disorder events.
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Injúria Renal Aguda , Hiperpotassemia , Hipotensão , Falência Renal Crônica , Insuficiência Renal Crônica , Humanos , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/epidemiologia , Albuminúria/induzido quimicamente , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/induzido quimicamente , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , EdemaRESUMO
PURPOSE: The discontinuation of fertility treatment could decrease the chances of achieving parenthood for infertile patients and often leads to economic loss and medical resource waste. However, the evidence on the factors associated with discontinuation is unclear and inconsistent in the context of fertility treatment. This scoping review aimed to summarize the evidence on factors associated with discontinuation in fertility treatment, identify the current knowledge gap, and generate recommendations for future research. METHODS: We searched PubMed, Embase, The Cochrane Library, Web of Science, CINAHL, American Psychological Association, and http://clinicaltrials.gov from inception to June 2023 without language or time restrictions. We also searched the grey literature in Open Grey and Google Scholar and hand-searched the reference lists of relevant studies to identify potentially eligible studies. Publications that studied factors associated with discontinuation in fertility treatment were included. The identified factors were mapped to the World Health Organization's treatment adherence model. RESULTS: Thirty-seven articles involving 41,973 infertile patients from 13 countries were included in this scoping review. All studies identified the factors from the perspective of patients, except for one that described the factors from the healthcare providers' perspective. A total of 42 factors were identified, with most of them belonging to the patient-related dimension, followed by socio-economic-related, treatment-related, condition-related, and healthcare system-related dimensions. Female education level, social support, and insurance coverage decreased the likelihood of treatment discontinuation, whereas multiparous women, male infertility, depression, higher infertility duration, and treatment duration increased the likelihood of treatment discontinuation. Age, education level, and ethnicity are the commonly nonmodifiable factors for treatment discontinuation, while insurance coverage, depression, and anxiety symptoms are among some of the more commonly reported modifiable factors. CONCLUSION: This is the first scoping review examining and synthesizing evidence on the factors influencing of discontinuation in fertility treatment. This review could inform researchers, clinicians, and policymakers to address modifiable barriers and facilitators to develop personalized and multicomponent interventions that could improve the discontinuation in fertility treatment.
Assuntos
Fertilidade , Infertilidade , Humanos , Masculino , Feminino , Infertilidade/terapia , Infertilidade/psicologia , Técnicas de Reprodução Assistida/psicologia , Pessoal de Saúde , AnsiedadeRESUMO
BACKGROUND: Domestication and introduction of dairy animals facilitated the permanent human occupation of the Tibetan Plateau. Yet the history of dairy pastoralism in the Tibetan Plateau remains poorly understood. Little is known how Tibetans adapted to milk and dairy products. RESULTS: We integrated archeological evidence and genetic analysis to show the picture that the dairy ruminants, together with dogs, were introduced from West Eurasia into the Tibetan Plateau since ~ 3600 years ago. The genetic admixture between the exotic and indigenous dogs enriched the candidate lactase persistence (LP) allele 10974A > G of West Eurasian origin in Tibetan dogs. In vitro experiments demonstrate that - 13838G > A functions as a LP allele in Tibetans. Unlike multiple LP alleles presenting selective signatures in West Eurasians and South Asians, the de novo origin of Tibetan-specific LP allele - 13838G > A with low frequency (~ 6-7%) and absence of selection corresponds - 13910C > T in pastoralists across eastern Eurasia steppe. CONCLUSIONS: Results depict a novel scenario of genetic and cultural adaptations to diet and expand current understanding of the establishment of dairy pastoralism in the Tibetan Plateau.
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Criação de Animais Domésticos , Povo Asiático , Dieta , Leite , Animais , Cães/genética , Humanos , Tibet , RuminantesRESUMO
PURPOSE: There have been insufficient data regarding the long-term results of unrestricted kinematically aligned total knee arthroplasty (unKATKA) in Asian patients. We investigated mid- to long-term clinical and radiological follow-up data of Korean patients after caliper-verified unKATKA of minimum 7.4-10 years including categorised data of postoperative tibial component, limb and knee alignment. Additionally, we analysed the preoperative distribution and postoperative restoration of coronal plane alignment of knee (CPAK) phenotypes. METHODS: This study is a retrospective analysis of 63 patients: 96 osteoarthritic underwent consecutive caliper-verified unKATKA between October 2013 and May 2016 by a single surgeon. Implant survivorship was investigated for revision for any reason. Each knee was categorised into an in-range or outlier group by three postoperative alignment parameters: tibial component, knee and limb alignment. Statistical analyses were done for any significant differences in clinical scores and implant survival rates between groups. Finally, all knees were classified into CPAK classification postoperatively and postoperatively. The CPAK restoration rate was calculated. RESULTS: Among 85 knees in the clinically confirmed group, implant survival was 98.8%. There was one case of revision due to periprosthetic fracture. The percentage postoperatively aligned in the varus (valgus) outlier range was 100% (0%) for tibial component, 16.7% (24.8%) for the knee alignment and 51% (0%) for the limb alignment. All three categories did not affect implant survival or clinical scores. Eighty one out of 96 knees (84.4%) were restored to their CPAK phenotype postoperatively. CONCLUSION: With the limitation of a case series having a small number of patients and gender deviation, our study suggests that caliper-verified unKATKA could be a good option regardless of geographical variation of constitutional alignment in patients with osteoarthritis (OA). LEVEL OF EVIDENCE: Level IV, therapeutic study.
Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Humanos , Artroplastia do Joelho/métodos , Estudos Retrospectivos , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Tíbia/cirurgia , Fenômenos BiomecânicosRESUMO
Since 2017, an infectious goose gout disease characterized by urate precipitation in viscera, mainly caused by novel goose astrovirus (GoAstV) infection, has emerged in the main goose-producing region of China. The current challenge in managing goose gout disease is largely due to the absence of a rapid and efficient detection method for the GoAstV pathogen. Notably, the potential application of immunosensors in detecting GoAstV has not yet been explored. Herein, a label-free PEC immunosensor was fabricated by using purchased TiO2 as the photoactive material and antibody against GoAstV P2 proteins as the specific recognition element. First, we successfully expressed the capsid spike domain P2 protein of ORF2 from GoAstV CHSH01 by using the pET prokaryotic expression system. Meanwhile, the polyclonal antibody against GoAstV capsid P2 protein was produced by purified protein. To our knowledge, this is the first establishment and preliminary application of the label-free photoelectrochemical immunosensor method in the detection of AstV. The PEC immunosensor had a linear range of 1.83 fg mL-1 to 3.02 ng mL-1, and the limit of detection (LOD) was as low as 0.61 fg mL-1. This immunosensor exhibited high sensitivity, great specificity, and good stability in detecting GoAstV P2 proteins. To evaluate the practical application of the immunosensor in real-world sample detection, allantoic fluid from goose embryos was collected as test samples. The results indicated that of the eight positive samples, one false negative result was detected, while both negative samples were accurately detected, suggesting that the constructed PEC immunosensor had good applicability and practical application value, providing a platform for the qualitative detection of GoAstV.
Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Limite de Detecção , Titânio , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Animais , Imunoensaio/métodos , Titânio/química , Gansos , Proteínas do Capsídeo/imunologia , Proteínas do Capsídeo/química , Avastrovirus/química , Avastrovirus/imunologia , Anticorpos Imobilizados/imunologia , Anticorpos Imobilizados/química , Anticorpos Antivirais/imunologia , Processos FotoquímicosRESUMO
BACKGROUND: Mammals are potential hosts for many infectious diseases. However, studies on the viral communities of herbivorous mammals in the Northwest Plateau are limited. Here, we studied the viral communities of herbivorous mammals in the Northwest Plateau using virus metagenomic analysis to analyze and compare the viral community composition of seven animal species. RESULTS: By library construction and next-generation sequencing, contigs and singlets reads with similar viral sequences were classified into 24 viral families. Analyzed from the perspective of sampling areas, the virus community composition was relatively similar in two areas of Wuwei and Jinchang, Gansu Province. Analyzed from the perspective of seven animal species, the viral reads of seven animal species were mostly ssDNA and dominated by CRESS-DNA viruses. Phylogenetic analysis based on viral marker genes indicated that CRESS-DNA viruses and microviruses have high genetic diversity. In addition to DNA viruses, nodaviruses, pepper mild mottle viruses and picornaviruses were RNA viruses that we performed by phylogenetic analysis. The CRESS-DNA viruses and nodaviruses are believed to infect plants and insects, and microviruses can infect bacteria, identifying that they were likely from the diet of herbivorous mammals. Notably, two picornaviruses were identified from red deer and wild horse, showing that the picornavirus found in red deer had the relatively high similarity with human hepatitis A virus, and the picornavirus carried by wild horse could potentially form a new species within the Picornaviridae family. CONCLUSIONS: This study explored the herbivorous mammalian virus community in the Northwest Plateau and the genetic characteristics of viruses that potentially threaten human health. It reveals the diversity and stability of herbivorous mammalian virus communities in the Northwest Plateau and helps to expand our knowledge of various herbivorous mammalian potentially pathogenic viruses.
Assuntos
Brassicaceae , Cervos , Animais , Humanos , Filogenia , Verduras , Clonagem MolecularRESUMO
The diversity of Central Asians has been shaped by multiple migrations and cultural diffusion. Although ancient DNA studies have revealed the demographic changes of the Central Asian since the Bronze Age, the contribution of the ancient populations to the modern Central Asian remains opaque. Herein, we performed high-coverage sequencing of 131 whole genomes of Indo-European-speaking Tajik and Turkic-speaking Kyrgyz populations to explore their genomic diversity and admixture history. By integrating the ancient DNA data, we revealed more details of the origins and admixture history of Central Asians. We found that the major ancestry of present-day Tajik populations can be traced back to the admixture of the Bronze Age Bactria-Margiana Archaeological Complex and Andronovo-related populations. Highland Tajik populations further received additional gene flow from the Tarim mummies, an isolated ancient North Eurasian-related population. The West Eurasian ancestry of Kyrgyz is mainly derived from Historical Era populations in Xinjiang of China. Furthermore, the recent admixture signals detected in both Tajik and Kyrgyz are ascribed to the expansions of Eastern Steppe nomadic pastoralists during the Historical Era.
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DNA Antigo , Múmias , Povo Asiático/genética , Etnicidade , Fluxo Gênico , Genética Populacional , HumanosRESUMO
Forest carbon is a large and uncertain component of the global carbon cycle. An important source of complexity is the spatial heterogeneity of vegetation vertical structure and extent, which results from variations in climate, soils, and disturbances and influences both contemporary carbon stocks and fluxes. Recent advances in remote sensing and ecosystem modeling have the potential to significantly improve the characterization of vegetation structure and its resulting influence on carbon. Here, we used novel remote sensing observations of tree canopy height collected by two NASA spaceborne lidar missions, Global Ecosystem Dynamics Investigation and ICE, Cloud, and Land Elevation Satellite 2, together with a newly developed global Ecosystem Demography model (v3.0) to characterize the spatial heterogeneity of global forest structure and quantify the corresponding implications for forest carbon stocks and fluxes. Multiple-scale evaluations suggested favorable results relative to other estimates including field inventory, remote sensing-based products, and national statistics. However, this approach utilized several orders of magnitude more data (3.77 billion lidar samples) on vegetation structure than used previously and enabled a qualitative increase in the spatial resolution of model estimates achievable (0.25° to 0.01°). At this resolution, process-based models are now able to capture detailed spatial patterns of forest structure previously unattainable, including patterns of natural and anthropogenic disturbance and recovery. Through the novel integration of new remote sensing data and ecosystem modeling, this study bridges the gap between existing empirically based remote sensing approaches and process-based modeling approaches. This study more generally demonstrates the promising value of spaceborne lidar observations for advancing carbon modeling at a global scale.
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Carbono , Ecossistema , Tecnologia de Sensoriamento Remoto , Florestas , ÁrvoresRESUMO
BACKGROUND: Porcine circovirus type 2 (PCV2) has caused great economic losses in the global pig industry. There have been published records of wild rats acting as the reservoirs of PCV2 (only PCV2a and PCV2b), but almost all of which were related to the PCV2-infected swine herds. RESULTS: In this study, we carried out the detection, amplification, and characterization of novel PCV2 strains in wild rats that were captured far from pig farms. Nested PCR assay demonstrated that the kidney, heart, lung, liver, pancreas, and large and small intestines of rats were screened positive for PCV2. We subsequently sequenced two full genomes of PCV2 in positive sample pools, designated as js2021-Rt001 and js2021-Rt002. Genome sequence analysis indicated that they had the highest similarity to nucleotide sequences of porcine-origin PCV2 isolates in Vietnam. Phylogenetically, js2021-Rt001 and js2021-Rt002 were a part of the PCV2d genotype cluster, which is a predominant genotype circulating worldwide in recent years. The antibody recognition regions, immunodominant decoy epitope, and heparin sulfate binding motif of the two complete genome sequences coincided with those previously reported. CONCLUSIONS: Our research reported the genomic characterization of two novel PCV2 strains (js2021-Rt001 and js2021-Rt002) and provided the first supported evidence that PCV2d could naturally infect wild rats in China. However, whether the newly identified strains have potential for circulating in nature in vertical and horizontal transmission or inter-species jumping between rats and pigs needs further research.
Assuntos
Infecções por Circoviridae , Circovirus , Doenças dos Suínos , Animais , Suínos , Ratos , Infecções por Circoviridae/veterinária , Filogenia , Fazendas , Viroma , Doenças dos Suínos/epidemiologia , Genótipo , China/epidemiologiaRESUMO
The rise and expansion of Tibetan Empire in the 7th to 9th centuries AD affected the course of history across East Eurasia, but the genetic impact of Tibetans on surrounding populations remains undefined. We sequenced 60 genomes for four populations from Pakistan and Tajikistan to explore their demographic history. We showed that the genomes of Balti people from Baltistan comprised 22.6-26% Tibetan ancestry. We inferred a single admixture event and dated it to about 39-21 generations ago, a period that postdated the conquest of Baltistan by the ancient Tibetan Empire. The analyses of mitochondrial DNA, Y, and X chromosome data indicated that both ancient Tibetan males and females were involved in the male-biased dispersal. Given the fact that the Balti people adopted Tibetan language and culture in history, our study suggested the impact of Tibetan Empire on Baltistan involved dominant cultural and minor demic diffusion.
Assuntos
Fluxo Gênico , Genoma Humano , Feminino , Humanos , Masculino , Paquistão , Tibet/etnologia , Sequenciamento Completo do GenomaRESUMO
The pangolin is the only scaly mammal in the world and also an important reservoir of pathogenic viruses. Habitat loss and poaching have been shrinking the survival range of pangolins. More information on pangolin virus populations is needed to better understand and assess potential disease risks. In this study, viral metagenomic data were used to reinvestigate the virome in pangolin lung tissue. Complete genome sequences of two novel anelloviruses were acquired and clustered with the referenced feline strains belonging to genus Tettorquevirus and genus Etatorquevirus, respectively. Two genomes belonging to the genus Gemykibivirus, and species Bat-associated cyclovirus 9 were detected, respectively. One genome with a large contig belonging to the genus Senecavirus were also characterized, according to phylogenetic analysis, which can be presumed to be a novel species. In addition, a full genome of endogenous retroviruse (ERV) was assembled from the lungs of pangolin, and this virus may have the possibility of cross-species transmission during the evolution. This virological investigation has increased our understanding of the virome carried by pangolins and provided a reference baseline for possible zoonotic infectious diseases in the future.
Assuntos
Anelloviridae , Pangolins , Anelloviridae/genética , Animais , Gatos , Genoma Viral , Humanos , Metagenômica , FilogeniaRESUMO
The gut microbiome plays an essential role in the human health and dysbiosis has been implicated in numerous diseases. Coxsackievirus B3 infects millions of humans yearly and yet limited research has explored dynamic alterations of the gut virome after infection. Here, we established the mouse model of Coxsackievirus B3 infection and collected fecal samples at several time points to investigate alterations of the gut virome using viral metagenomic analysis. We found that the mice virome was dominated by Caudovirales and Microviridae, and phylogenetic analyses showed that both Caudovirales and Microviridae had high diversity. The gut virome had significant variations with the increase of Caudovirales and the decrease of Microviridae after infection. We proposed that Caudovirales and Microviridae may be biomarkers for the Coxsackievirus infection process. This study provides a reference for the dynamic changes of the gut virome after human Enterovirus infection, which may help guide the rational drug use in clinical treatment and provide new ideas for preventing Enterovirus infection.
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Infecções por Coxsackievirus , Infecções por Enterovirus , Microviridae , Animais , Humanos , Camundongos , Filogenia , ViromaRESUMO
BACKGROUND: Bats were identified as a natural reservoir of emerging and re-emerging infectious pathogens threatening human health and life. METHODS: This study collected 21 fecal samples of Hipposideros armiger in Mengla County of Xishuangbanna Prefecture Yunnan Province to combine one pool for viral metagenomic sequencing. RESULTS: Two nearly complete genomes of parechoviruses, BPeV11 and BPeV20, were sequenced. Genome analysis revealed that BPeV11 and BPeV20 follow a 3-3-4 genome layout: 5' UTR-VP0-VP3-VP1-2A-2B-2C-3A-3B-3C-3D-3' UTR. The prevalence of BPev11 and BPev20 by Nested-PCR showed that 1 of 21 fecal samples was positive. Based on amino acid identity comparison and phylogenetic analysis of P1, 2C, and 3D, BPeV11 and BPeV20 were closely related to but distinct from FPeVs. CONCLUSION: It was probably proposed to be a novel species in the genus Parechovirus of the family Picornaviridae. The isolation of BPev11 and BPev20 from H. armiger in China is the first complete genome of parechovirus isolations from bat feces of the genus Hipposideros.
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Quirópteros , Parechovirus , Infecções por Picornaviridae , Regiões 5' não Traduzidas , Animais , China , Genoma Viral , Humanos , Parechovirus/genética , Filogenia , Infecções por Picornaviridae/veterináriaRESUMO
We used viral metagenomics and next-generation sequencing to identify a novel strain of bocaparvovirus in the intestinal tract of tufted deer (Elaphodus cephalophus), tentatively named "Elaphodus cephalophus bocaparvovirus" (ECBOV). A nearly complete genome sequence of 5,354 nucleotides was obtained, which had the typical genome organization and protein motifs of a bocaparvovirus. Sequence comparisons and phylogenetic analysis revealed that ECBOV may be a new ungulate bocaparvovirus. The identification and characterization of viruses in wildlife will facilitate our understanding of genetic evolution and cross-species transmission and thus further reduce the potential threat to human and animal health.
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Bocavirus , Cervos , Animais , Bocavirus/genética , China , Genoma Viral , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Metagenômica , FilogeniaRESUMO
To explore the current state of research on off-label drug use in children and identify the existing research gaps in this topic. Six literature databases were searched to identify studies focusing exclusively on off-label drug use in children (aged < 18 years) published in Chinese or English between 2016 and 2021. We also searched clinicaltrials.gov for pediatric clinical trials conducted in the same period and compared the numbers of studies on off-label use and clinical trials for the most commonly reported drugs and drug types. Our search revealed 568 studies on off-label drug use. Almost half of the studies (n = 240) were cross-sectional. A total of 212 specific drugs or drug types were addressed in 361 studies, the most frequent being antipsychotic agents (n = 12), dexmedetomidine (n = 10), and rituximab (n = 8). Antipsychotic agents were also the most common type of drug examined in clinical trials in children. We identified a total of 435 different types of off-label use, the top three being unapproved indication (n = 157), population (n = 96), or age (n = 36). Only about one-third of the studies reported collecting informed consent (n = 195) or having ethics committee approval (n = 166). Conclusions: Off-label use of antipsychotics in children is widely reported in the literature. We suggest pediatric researchers to consider the number of studies on off-label use and existing clinical trials on different drugs when selecting target drugs for new studies and systematic reviews. What is Known: ⢠There exist a large number of studies on off-label drug use in children. What is New: ⢠This is the first scoping review of studies on off-label drug use in children. ⢠Off-label use of antipsychotic agents is widely reported.
Assuntos
Antipsicóticos , Pediatria , Antipsicóticos/uso terapêutico , Criança , Rotulagem de Medicamentos , Humanos , Consentimento Livre e Esclarecido , Uso Off-LabelRESUMO
BACKGROUND: Prenatal anxiety is a common concern which may have adverse effects on maternal and infant health outcomes. Studies addressing needs-based education interventions for prenatal anxiety are limited. AIM: To explore the effects of needs-based education on alleviating prenatal anxiety among advanced multiparas when compared with routine prenatal health education. METHODS: A total of 86 advanced multiparas were randomized into the intervention group (n = 43) or the control group (n = 43) in this study. The control group received routine prenatal care. The intervention group received five needs-based education programs presented by trained researchers. The Pregnancy-related Anxiety Questionnaire was used to evaluate changes in anxiety level of participants. Concurrent physiological parameters, including blood pressure, heart rate and non-stress test were also measured. RESULTS: Scores on the Pregnancy-related Anxiety Questionnaire of the intervention group were significantly lower than those of the control group (t = 4.21, P < 0.05). Systolic blood pressure (t = 3.64, P < 0.05) and heart rate (t = 2.39, P < 0.05) of the intervention group were also significantly lower than the control group whereas no differences were noted in diastolic blood pressure and non-stress test. CONCLUSION: A needs-based education program is an effective intervention strategy to allay prenatal anxiety in advanced multiparas. TRIAL REGISTRATION: The trial was retrospectively registered in the Chinese Clinical Trial Registry as number ChiCTR2100047552 .
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Ansiedade , Cuidado Pré-Natal , Ansiedade/terapia , Transtornos de Ansiedade , Feminino , Educação em Saúde , Frequência Cardíaca/fisiologia , Humanos , GravidezRESUMO
BACKGROUND: The "Law on Doctors of the People's Republic of China," which was officially implemented on March 1, 2022, emphasizes the requirements for rational drug use and the necessity for appropriate management of off-label drug use. The safety and ethical considerations related to off-label drug use are different in children than in adults. There is so far no management guideline for pediatric off-label use of drugs in China, and the applicability of foreign guidelines is limited. Establishing a localized evidence-based management guideline for pediatric off-label use of drugs to support the national legislation and clinical practice is of critical importance. METHODS: We established a guideline working group, including experts from a broad range of disciplines and developed recommendations following the guidance of the World Health Organization Handbook and the Chinese Medical Association. The following themes were identified by questionnaires and expert interviews to be of great concern in the management of off-label drug use in children: general principles and characteristics of management of pediatric off-label drug use; establishment of expert committees; evidence evaluation; risk-benefit assessment; informed consent; monitoring and assessment of the risk; and monitoring and patient education. Two rounds of Delphi surveys were organized to determine the final recommendations of this guideline. We graded the recommendations based on the body of evidence, referring to the evaluation tool of the Evidence-based management (EBMgt) and the Oxford Center for Evidence-Based Medicine: Level of Evidence (March 2009). RESULTS: We developed the first guideline for the management of pediatric off-label use of drugs in China. CONCLUSIONS: The guideline is to offer guidance for pediatricians, pharmacists, medical managers, policymakers, and primary care physicians on how to manage off-label drug use in pediatrics and to provide recommendations for Chinese healthcare policy in the future.
Assuntos
Uso Off-Label , Médicos , Adulto , Criança , China , Rotulagem de Medicamentos , Medicina Baseada em Evidências , Humanos , PediatrasRESUMO
The outbreaks caused by RNA and DNA viruses, such as SARS-CoV-2 and monkeypox, pose serious threats to human health. The RLR and cGAS-STING pathways contain major cytoplasmic sensors and signaling transduction axes for host innate antiviral immunity. In physiological and virus-induced pathological states, the activation and inactivation of these signal axes are tightly controlled, especially post-translational modifications (PTMs). E3 ubiquitin ligases (E3s) are the direct manipulator of ubiquitin codons and determine the type and modification type of substrate proteins. Therefore, members of the E3s family are involved in balancing the host's innate antiviral immune responses, and their functions have been extensively studied over recent decades. In this study, we overviewed the mechanisms of different members of three E3s families that mediate the RLR and cGAS-STING axes and analyzed them as potential molecular targets for the prevention and treatment of virus-related diseases.
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COVID-19 , Viroses , Humanos , Ubiquitina , Ubiquitina-Proteína Ligases , Proteínas de Membrana/metabolismo , SARS-CoV-2/metabolismo , Nucleotidiltransferases/metabolismo , Imunidade InataRESUMO
Calf diarrhoea has been a major cause of economic losses in the global dairy industry. Many factors, including multiple pathogen infections, can directly or indirectly cause calf diarrhoea. This study compared the faecal virome between 15 healthy calves and 15 calves with diarrhoea. Significantly lower diversity of viruses was found in samples from animals with diarrhoea than those in the healthy ones, and this feature may also be related to the age of the calves. Viruses belonging to the families Astroviridae and Caliciviridae that may cause diarrhoea in dairy calves have been characterized, which revealed that reads of caliciviruses and astroviruses in diarrhoea calves were much higher than those in healthy calves. Five complete genomic sequences closely related to Smacoviridae have been identified, which may participate in the regulation of the gut virus community ecology of healthy hosts together with bacteriophages. This research provides a theoretical basis for further understanding of known or potential enteric pathogens related to calf diarrhoea.
Assuntos
Doenças dos Bovinos/virologia , Bovinos/virologia , Diarreia/veterinária , Intestinos/virologia , Viroma , Animais , Caliciviridae/classificação , Caliciviridae/genética , Caliciviridae/isolamento & purificação , Vírus de DNA/classificação , Vírus de DNA/genética , Vírus de DNA/isolamento & purificação , Indústria de Laticínios , Diarreia/virologia , Fezes/virologia , Genoma Viral , Mamastrovirus/classificação , Mamastrovirus/genética , Mamastrovirus/isolamento & purificação , Metagenômica , FilogeniaRESUMO
Pangolin metagenomic data obtained from public databases were used to assemble partial or complete viral genomes showing genetic relationship to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Sendai virus, flavivirus, picornavirus, parvovirus, and genomovirus, respectively. Most of these virus genomes showed genomic recombination signals. Phylogeny based on the SARS-CoV-2-related virus sequences assembled in this study and those recently published indicated that pangolin SARS-CoV-2-related viruses were clustered into two sub-lineages according to geographic sampling sites. These findings suggest the need for further pangolin samples, from different countries, to be collected and analyzed for coronavirus to elucidate whether pangolins are intermittent hosts for SARS-CoV-2.