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BACKGROUND: This study aims to investigate potential interactions between maternal smoking around birth (MSAB) and type 2 diabetes (T2D) pathway-specific genetic risks in relation to the development of T2D in offspring. Additionally, it seeks to determine whether and how nutritional factors during different life stages may modify the association between MSAB and risk of T2D. METHODS: This study included 460,234 participants aged 40 to 69 years, who were initially free of T2D from the UK Biobank. MSAB and breastfeeding were collected by questionnaire. The Alternative health eating index(AHEI) and dietary inflammation index(DII) were calculated. The polygenic risk scores(PRS) of T2D and pathway-specific were established, including ß-cell function, proinsulin, obesity, lipodystrophy, liver function and glycated haemoglobin(HbA1c). Cox proportion hazards models were performed to evaluate the gene/diet-MSAB interaction on T2D. The relative excess risk due to additive interaction (RERI) were calculated. RESULTS: During a median follow-up period of 12.7 years, we identified 27,342 cases of incident T2D. After adjustment for potential confounders, participants exposed to MSAB had an increased risk of T2D (HR=1.11, 95%CI:1.08-1.14), and this association remained significant among the participants with breastfeeding (HR= HR=1.10, 95%CI: 1.06-1.14). Moreover, among the participants in the highest quartile of AHEI or in the lowest quartile of DII, the association between MSAB and the increased risk of T2D become non-significant (HR=0.94, 95%CI: 0.79-1.13 for AHEI; HR=1.09, 95%CI:0.99-1.20 for DII). Additionally, the association between MSAB and risk of T2D became non-significant among the participants with lower genetic risk of lipodystrophy (HR=1.06, 95%CI:0.99-1.14), and exposed to MSAB with a higher genetic risk for ß-cell dysfunction or lipodystrophy additively elevated the risk of T2D(RERI=0.18, 95%CI:0.06-0.30 for ß-cell function; RERI=0.16, 95%CI:0.04-0.28 for lipodystrophy). CONCLUSIONS: This study indicates that maintaining a high dietary quality or lower dietary inflammation in diet may reduce the risk of T2D associated with MSAB, and the combination of higher genetic risk of ß-cell dysfunction or lipodystrophy and MSAB significantly elevate the risk of T2D in offspring.
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Diabetes Mellitus Tipo 2 , Lipodistrofia , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/etiología , Estudios Prospectivos , Biobanco del Reino Unido , Bancos de Muestras Biológicas , Factores de Riesgo , Inflamación/complicaciones , Fumar , Lipodistrofia/complicacionesRESUMEN
OBJECTIVES: The performance of the new Respiratory Pathogen panel (fluorescent probe melting curve, FPMC) for the qualitative detection of 12 organisms (chlamydia pneumoniae, mycoplasma pneumoniae, adenovirus, influenza A virus, influenza B virus, parainfluenza virus, rhinovirus, etc.) was assessed. METHODS: Prospectively collected nasopharyngeal swab (NPS) and sputum specimens (n = 635) were detected by using the FPMC panel, with the Sanger sequencing method as the comparative method. RESULTS: The overall percent concordance between the FPMC analysis method and the Sanger sequencing method was 100% and 99.66% for NPS and sputum specimens, respectively. The FPMC testified an overall positive percent concordance of 100% for both NPS and sputum specimens. The FPMC analysis method also testified an overall negative percent concordance of 100% and 99.38% for NPS and sputum specimens, respectively. CONCLUSIONS: The FPMC analysis method is a stable and accurate assay for rapid, comprehensive detecting for respiratory pathogens.
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Técnicas de Diagnóstico Molecular , Nasofaringe , Infecciones del Sistema Respiratorio , Esputo , Humanos , Esputo/microbiología , Esputo/virología , Nasofaringe/virología , Nasofaringe/microbiología , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/microbiología , Técnicas de Diagnóstico Molecular/métodos , Virus/aislamiento & purificación , Virus/genética , Virus/clasificación , Adulto , Estudios Prospectivos , Persona de Mediana Edad , Adolescente , Femenino , Adulto Joven , Niño , Masculino , Anciano , Preescolar , Lactante , Manejo de Especímenes/métodos , Sensibilidad y Especificidad , Anciano de 80 o más AñosRESUMEN
PURPOSE: Donor-derived infection (DDI) has become an important factor affecting the prognosis of lung transplantation patients. The risks versus benefits of using donor organs infected with multidrug-resistant organisms (MDRO), especially carbapenem-resistant organisms (CRO), are frequently debated. Traditional microbial culture and antimicrobial susceptibility testing at present fail to meet the needs of quick CRO determination for donor lungs before acquisition. In this study, we explored a novel screening method by using Xpert® Carba-R assay for CRO in donor lungs in a real-time manner to reduce CRO-associated DDI mortality. METHODS: This study was registered on chictr.org.cn (ChiCTR2100053687) on November 2021. In the Xpert Carba-R screening group, donor lungs were screened for CRO infection by the Xpert Carba-R test on bronchoalveolar fluid (BALF) before acquisition. If the result was negative, donor lung acquisition and subsequent lung transplantation were performed. In the thirty-five potential donors, nine (25.71%) with positive Xpert Carba-R results in BALF were declined for lung transplantation. Twenty-six recipients and the matching CRO-negative donor lungs (74.29%) were included in the Xpert Carba-R screening group. In the control group, nineteen recipients underwent lung transplants without Xpert Carba-R screening. The incidence and mortality of CRO-associated DDI were collected and contrasted between the two groups. RESULTS: Multivariate analysis showed that CRO-related death due to DDI within 60 days was significantly lower in the Xpert Carba-R screening group than that in the control group (OR = 0.05, 95% CI 0.003-0.74, p = 0.03). CONCLUSION: Real-time CRO screening of donor lungs before transplantation at the point of care by the Xpert Carba-R helps clinicians formulate lung transplantation strategies quickly and reduces the risk of subsequent CRO infection improving the prognosis of lung transplantation.
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Carbapenémicos , Trasplante de Pulmón , Humanos , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Receptores de Trasplantes , Pulmón , Tamizaje Masivo , Trasplante de Pulmón/efectos adversosRESUMEN
Ecdysis-triggering hormone (ETH) is a neuropeptide hormone characterized by a conserved KxxKxxPRx amide structure widely identified in arthropods. While its involvement in the regulation of molting and reproduction in insects is well-established, its role in crustaceans has been overlooked. This study aimed to de-orphanise a receptor for ETH in the mud crab Scylla paramamosain and explore its potential impact on ovarian development. A 513-amino-acid G protein-coupled receptor for ETH (SpETHR) was identified in S. paramamosain, exhibiting a dose-dependent activation by SpETH with an EC50 value of 75.18 nM. Tissue distribution analysis revealed SpETH was in the cerebral ganglion and thoracic ganglion, while SpETHR was specifically expressed in the ovary, hepatopancreas, and Y-organ of female crabs. In vitro experiments demonstrated that synthetic SpETH (at a concentration of 10-8 M) significantly increased the expression of SpVgR in the ovary and induced ecdysone biosynthesis in the Y-organ. In vivo experiments showed a significant upregulation of SpEcR in the ovary and Disembodied and Shadow in the Y-organ after 12 h of SpETH injection. Furthermore, a 16-day administration of SpETH significantly increased 20E titers in hemolymph, gonadosomatic index (GSI) and oocyte size of S. paramamosain. In conclusion, our findings suggest that SpETH may play stimulatory roles in ovarian development and ecdysone biosynthesis by the Y-organ.
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A rapid, accurate, non-sputum-based triage test for diagnosing tuberculosis (TB) is a high-priority need. Cepheid developed a novel prototype blood test, Xpert Mycobacterium tuberculosis Host Response (Xpert-MTB-HR), which generates a TB score based on the mRNA expression of three genes. We conducted a case-control study with prospective recruitment to evaluate its accuracy in the clinic of the Wusheng County Centers for Disease Prevention and Control in China. We enrolled 149 TB patients, 248 other respiratory diseases (ORD) patients, and 193 healthy controls. In addition, whole-blood samples taken from TB patients after 2, 5, and 6 months of treatment were tested with Xpert-MTB-HR to evaluate its ability to monitor treatment response. Xpert-MTB-HR discriminated between TB and healthy controls with an area under the curve (AUC) of 0.912 (95% CI, 0.878-0.945). With the specificity of 70% envisioned for a triage test, its sensitivity was 90.1% (84.9%-94.6%). Xpert-MTB-HR discriminated between TB and ORD with an AUC of 0.798 (0.750-0.847), and at specificity of 70%, the sensitivity was only 75.8% (68.5%-82.8%). In patients determined by Ultra to have medium or high sputum bacillary loads, with specificity of 70%, the sensitivity for discriminating patients with TB from healthy controls was 100.0% (100.0-100.0) and from patients with ORD, 95.1% (89.8-100.0). The TB scores generally increased by 2 months of treatment and then remained stable. Xpert-MTB-HR met the criteria for a triage test to discriminate between TB and healthy controls, but not between TB and ORD, except when limited to patients with high sputum bacillary loads. Xpert-MTB-HR showed promise for monitoring response to treatment but needs to be further evaluated in larger prospective studies.
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Antibióticos Antituberculosos , Mycobacterium tuberculosis , Tuberculosis Pulmonar , Tuberculosis , Humanos , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiología , Estudios Prospectivos , Rifampin , Antibióticos Antituberculosos/uso terapéutico , Estudios de Casos y Controles , Sensibilidad y Especificidad , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Mycobacterium tuberculosis/genética , Esputo/microbiología , ChinaRESUMEN
The Xpert MTB/XDR assay met the critical need for etiologic diagnosis of tuberculosis and rifampin resistance in previous studies. However, its benefits in tailoring the treatment regimen and improving the outcome for patients with rifampin-resistant tuberculosis (RR-TB) require further investigation. In this study, the Xpert MTB/XDR assay was used to determine the resistance profile of second-line drugs for RR-TB patients in two registered multicenter clinical trials, TB-TRUST (NCT03867136) and TB-TRUST-plus (NCT04717908), with the aim of testing the efficacy of all-oral shorter regimens in RR-TB patients in China. Patients would receive the fluoroquinolone-based all-oral shorter regimen, the injectable-containing regimen, or the bedaquiline-based regimen depending on fluoroquinolone susceptibility by using Xpert MTB/XDR. Among the 497 patients performed with Xpert MTB/XDR, 128 (25.8%) had infections resistant to fluoroquinolones and/or second-line injectable drugs (SLIDs). A total of 371 participants were recruited for the trials, and whole-genome sequencing (WGS) was performed on all corresponding culture-positive baseline strains. Taking the WGS results as the standard, the accuracy of the Xpert MTB/XDR assay in terms of resistance detection was 95.2% to 99.0% for all drugs. A total of 33 cases had inconsistent results, 9 of which were due to resistance heterogeneity. Most of the patients (241/281, 85.8%) had sputum culture conversion at 2 months. In conclusion, the Xpert MTB/XDR assay has the potential to serve as a quick reflex test in patients with RR-TB, as detected via Xpert MTB/RIF, to provide a reliable drug susceptibility profile of the infecting Mycobacterium tuberculosis strain and to initiate optimized treatment promptly.
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Antibióticos Antituberculosos , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Tuberculosis , Humanos , Rifampin/farmacología , Rifampin/uso terapéutico , Antibióticos Antituberculosos/farmacología , Sensibilidad y Especificidad , Tuberculosis/diagnóstico , Mycobacterium tuberculosis/genética , Fluoroquinolonas/farmacología , Fluoroquinolonas/uso terapéutico , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Farmacorresistencia Bacteriana , Esputo/microbiologíaRESUMEN
A novel, molecularly imprinted, upconversion fluorescence probe (UCNP@MIFP) for sulfonamide sensing was fabricated by Pickering emulsion polymerization using UCNP@SiO2 particles as the stabilizer and sulfamethazine/sulfamerazine as the co-templates. The synthesis conditions of the UCNP@MIFP were optimized, and the synthesized probe was characterized by scanning electron microscopy, Fourier transform infrared spectrometer, thermogravimetric analyzer, and fluorescence spectrometer. The UCNP@MIFPs showed a good adsorption capacity and a fast kinetic feature for the template. The selectivity experiment revealed that the UCNP@MIFP has a broad-spectrum molecular recognition capability. Good linear relationships were obtained over the concentration range of 1-10 ng/mL for sulfamerazine, sulfamethazine, sulfathiazole, and sulfafurazole, with low limits of detection in the range of 1.37-2.35 ng/mL. The prepared UCNP@MIFP has the potential to detect four sulfonamide residues in food and environmental water.
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Quantum dot nanobeads (QBs) were used as signal source to develop competitive lateral flow immunoassay (LFIA) for the detection of chloramphenicol (CAP). The quantitative detection of CAP was achieved by calculating the total color difference (∆E) values of the test line (T line) using the images of test strips. QB-based LFIA (QBs-LFIA) allowed the effective dynamic linear detection of CAP in the range of 0.1-1.5 ng/mL. The limit of detection (LOD) was 3.0 ng/mL, which was 50 and 667 times lower than those achieved for two different brands of colloidal gold kits. The recoveries of CAP during real-sample detection were 82.82-104.91% at spiked levels of 0.1, 0.7, and 1.5 ng/mL. These results indicate that the developed QBs-LFIA facilitates the sensitive detection of CAP.
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Cloranfenicol , Puntos Cuánticos , Inmunoensayo/métodos , Límite de Detección , Oro ColoideRESUMEN
BACKGROUND: Patients with bacteremia due to carbapenem-resistant Enterobacterales (CRE) experience delays until appropriate therapy and high mortality rates. Rapid molecular diagnostics for carbapenemases and new ß-lactam/ß-lactamase inhibitors may improve outcomes. METHODS: We conducted an observational study of patients with CRE bacteremia from 2016 to 2018 at 8 New York and New Jersey medical centers and assessed center-specific clinical microbiology practices. We compared time to receipt of active antimicrobial therapy and mortality between patients whose positive blood cultures underwent rapid molecular testing for the Klebsiella pneumoniae carbapenemase (KPC) gene (blaKPC) and patients whose cultures did not undergo this test. CRE isolates underwent antimicrobial susceptibility testing by broth microdilution and carbapenemase profiling by whole-genome sequencing. We also assessed outcomes when ceftazidime-avibactam and polymyxins were used as targeted therapies. RESULTS: Of 137 patients with CRE bacteremia, 89 (65%) had a KPC-producing organism. Patients whose blood cultures underwent blaKPC PCR testing (n = 51) had shorter time until receipt of active therapy (median: 24 vs 50â hours; P = .009) compared with other patients (n = 86) and decreased 14-day (16% vs 37%; P = .007) and 30-day (24% vs 47%; P = .007) mortality. blaKPC PCR testing was associated with decreased 30-day mortality (adjusted odds ratio: .37; 95% CI: .16-.84) in an adjusted model. The 30-day mortality rate was 10% with ceftazidime-avibactam monotherapy and 31% with polymyxin monotherapy (P = .08). CONCLUSIONS: In a KPC-endemic area, blaKPC PCR testing of positive blood cultures was associated with decreased time until appropriate therapy and decreased mortality for CRE bacteremia, and ceftazidime-avibactam is a reasonable first-line therapy for these infections.
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Bacteriemia , Infecciones por Klebsiella , Humanos , Klebsiella pneumoniae , Antibacterianos/uso terapéutico , Carbapenémicos/farmacología , Infecciones por Klebsiella/tratamiento farmacológico , Ceftazidima/uso terapéutico , beta-Lactamasas/genética , Proteínas Bacterianas/genética , Compuestos de Azabiciclo/uso terapéutico , Combinación de Medicamentos , Inhibidores de beta-Lactamasas/uso terapéutico , Bacteriemia/tratamiento farmacológico , Pruebas de Sensibilidad MicrobianaRESUMEN
Nearly 40 years have elapsed since the invention of the PCR, with its extremely sensitive and specific ability to detect nucleic acids via in vitro enzyme-mediated amplification. In turn, more than 2 years have passed since the onset of the coronavirus disease 2019 (COVID-19) pandemic, during which time molecular diagnostics for infectious diseases have assumed a larger global role than ever before. In this context, we review broadly the progression of molecular techniques in clinical microbiology, to their current prominence. Notably, these methods now entail both the detection and quantification of microbial nucleic acids, along with their sequence-based characterization. Overall, we seek to provide a combined perspective on the techniques themselves, as well as how they have come to shape health care at the intersection of technologic innovation, pathophysiologic knowledge, clinical/laboratory logistics, and even financial/regulatory factors.
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COVID-19 , Enfermedades Transmisibles , Ácidos Nucleicos , Humanos , Patología Molecular , COVID-19/diagnóstico , Técnicas de Amplificación de Ácido Nucleico/métodos , Enfermedades Transmisibles/diagnóstico , Técnicas de Diagnóstico Molecular/métodosRESUMEN
Rapid and accurate detection of carriers of carbapenemase-producing organisms (CPO) in hospitalized patients is critical for infection control and prevention. This study aimed to evaluate a pooling strategy for the detection of carbapenem resistance genes (CRG) in multiple specimens using the Xpert Carba-R test. Two rectal swabs each were collected from 415 unique patients. One swab was tested by Carba-R on the five specimen-pooled strategy. The other swab was tested individually by culture followed by DNA sequence analysis for CRG as the reference. At the first 5:1 pooling testing, 22 of 83 pools were positive, which yielded 34 positives from individual specimens when positive pools were subsequently retested. All individual specimens in the 61 negative pools were retested as negative by Carba-R. Among the 34 Carba-R-positive samples, 30 and four were positive and negative, respectively, by culture and sequencing. The remaining 381 Carba-R-negative specimens were also negative by culture and sequencing. Overall sensitivity, specificity, positive predictive value, and negative predictive value of the 5:1 pooled screening were 100.0% (95% confidence interval [CI] = 85.9% to 100%), 99.0% (95% CI = 97.2% to 99.7%), 88.2% (95% CI = 71.6% to 96.2%), and 100.0% (95% CI = 98.8% to 100%), respectively. Using the 5:1 pooling strategy, our study completed CRG screening in 414 patients with 193 reagents with significant cost savings. The 5:1 pooling strategy using the Carba-R test showed a potential method for screening CRG from rectal swabs with good sensitivity and decreased cost.
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Proteínas Bacterianas , beta-Lactamasas , Humanos , Sensibilidad y Especificidad , Proteínas Bacterianas/genética , beta-Lactamasas/genética , Valor Predictivo de las Pruebas , Carbapenémicos/farmacologíaRESUMEN
BACKGROUND: The relationship between serum selenium level and gestational diabetes mellitus (GDM) is controversial. The purpose is to update and summarize previous studies to understand the relationship in more detail. METHODS: PubMed, The Cochrane Library, EMBASE, Web of science, CNKI, WANFANG DATA and Cqvip were searched for studies published up to 3 September 2021. The random-effects model was used to measure the combined estimation. The overall effect was reported in a standard mean difference (SMD) and 95% confidence interval (95% CI). All data were analysed by Review Manager 5.4. RESULTS: Twenty-seven studies involving 1588 patients with GDM and 2450 healthy pregnant women contributed to this meta-analysis. Selenium level was significantly lower in women with GDM than those without GDM (SMD = -1.29; 95% CI: -1.60 to -0.97, p < 0.00001). Subgroup analyses showed that such trend was consistent within the non-European population (Asia: SMD = -1.44; 95% CI: -1.79 to -1.08, p < 0.00001; Africa: SMD = -2.62; 95% CI: -4.50 to -0.74, p = 0.006) and in the second and third trimesters (the second trimester: SMD = -1.41; 95% CI: -1.82 to -0.99, p < 0.00001; the third trimester: SMD = -1.54; 95% CI: -2.09 to -0.98, p < 0.00001), but not within the European population (SMD = -0.47; 95% CI: -1.09 to 0.16, p = 0.14) or in the first trimester (SMD = -0.52; 95% CI: -1.13 to 0.10, p = 0.10). CONCLUSIONS: This meta-analysis showed that the serum selenium level of patients with GDM was lower than that in healthy pregnant women, especially within the non-European population and in the second and third trimesters.
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Diabetes Gestacional , Selenio , Femenino , Humanos , Embarazo , Primer Trimestre del Embarazo , Segundo Trimestre del Embarazo , Tercer Trimestre del EmbarazoRESUMEN
A novel fluorescence platform was fabricated for enrofloxacin determination by using cDNA-modified dipeptide fluorescence nanoparticles (FDNP-cDNA) and aptamer-modified magnetic Fe3O4 nanoparticles (Fe3O4-Apt). The FDNP were prepared via tryptophan-phenylalanine self-assembling. When magnetic Fe3O4-Apt incubated with standard solution or sample extracts, the target enrofloxacin was selectively captured by the aptamer on the surface of the Fe3O4 nanoparticles. After removing interference by washing with phosphate-buffered saline, the FDNP-cDNA was added, which can bind to the aptamer on the surface of the Fe3O4 nanoparticles not occupied by the analyte. The higher the concentration of the target enrofloxacin in the standard or sample solution is, the less the FDNP-cDNA can be bound with the Fe3O4 nanoparticles, and the more the FDNP-cDNA can be observed in the supernatant. Fluorescence intensity (Ex/Em = 310/380 nm) increased linearly in the enrofloxacin concentration range 0.70 to 10.0 ng/mL with a detection limit of 0.26 ng/mL (S/N = 3). Good recoveries (88.17-99.30%) were obtained in spiked lake water, chicken, and eel samples with relative standard deviation of 2.7-6.2% (n = 3).
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Aptámeros de Nucleótidos/química , Dipéptidos/química , Enrofloxacina/análisis , Colorantes Fluorescentes/química , Nanopartículas/química , Contaminantes Químicos del Agua/análisis , Animales , Técnicas Biosensibles , Pollos , ADN Complementario/química , Anguilas , Lagos , Espectrometría de FluorescenciaRESUMEN
A 10:1 pooled test strategy on-site at an airport of China was pursued, resulting in increased test throughput, limited use of reagents, and increased testing efficiency without loss of sensitivity. This testing approach has the potential to reduce the need for contact tracing when the results are delivered first time.
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COVID-19 , Aeropuertos , China/epidemiología , Trazado de Contacto , Humanos , Tamizaje Masivo , SARS-CoV-2RESUMEN
The 2019 novel coronavirus disease (COVID-19) now is considered a global public health emergency. One of the unprecedented challenges is defining the optimal therapy for those patients with severe pneumonia and systemic manifestations of COVID-19. The optimal therapy should be largely based on the pathogenesis of infections caused by this novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the onset of COVID-19, there have been many prepublications and publications reviewing the therapy of COVID-19 as well as many prepublications and publications reviewing the pathogenesis of SARS-CoV-2. However, there have been no comprehensive reviews that link COVID-19 therapies to the pathogenic mechanisms of SARS-CoV-2. To link COVID-19 therapies to pathogenic mechanisms of SARS-CoV-2, we performed a comprehensive search through MEDLINE, PubMed, medRxiv, EMBASE, Scopus, Google Scholar, and Web of Science using the following keywords: COVID-19, SARS-CoV-2, novel 2019 coronavirus, pathology, pathologic, pathogenesis, pathophysiology, coronavirus pneumonia, coronavirus infection, coronavirus pulmonary infection, coronavirus cardiovascular infection, coronavirus gastroenteritis, coronavirus autopsy findings, viral sepsis, endotheliitis, thrombosis, coagulation abnormalities, immunology, humeral immunity, cellular immunity, inflammation, cytokine storm, superantigen, therapy, treatment, therapeutics, immune-based therapeutics, antiviral agents, respiratory therapy, oxygen therapy, anticoagulation therapy, adjuvant therapy, and preventative therapy. Opinions expressed in this review also are based on personal experience as clinicians, authors, peer reviewers, and editors. This narrative review linking COVID-19 therapies with pathogenic mechanisms of SARS-CoV-2 has resulted in six major therapeutic goals for COVID-19 therapy based on the pathogenic mechanisms of SARS-CoV-2. These goals are listed below: 1. The first goal is identifying COVID-19 patients that require both testing and therapy. This is best accomplished with a COVID-19 molecular test from symptomatic patients as well as determining the oxygen saturation in such patients with a pulse oximeter. Whether a symptomatic respiratory illness is COVID-19, influenza, or another respiratory pathogen, an oxygen saturation less than 90% means that the patient requires medical assistance. 2. The second goal is to correct the hypoxia. This goal generally requires hospitalization for oxygen therapy; other respiratory-directed therapies such as prone positioning or mechanical ventilation are often used in the attempt to correct hypoxemia due to COVID-19. 3. The third goal is to reduce the viral load of SARS-CoV-2. Ideally, there would be an oral antiviral agent available such as seen with the use of oseltamivir phosphate for influenza. This oral antiviral agent should be taken early in the course of SARS-CoV-2 infection. Such an oral agent is not available yet. Currently, two options are available for reducing the viral load of SARS-CoV-2. These are post-Covid-19 plasma with a high neutralizing antibody titer against SARS-CoV-2 or intravenous remdesivir; both options require hospitalization. 4. The fourth goal is to identify and address the hyperinflammation phase often seen in hospitalized COVID-19 patients. Currently, fever with an elevated C-reactive protein is useful for diagnosing this hyperinflammation syndrome. Low-dose dexamethasone therapy currently is the best therapeutic approach. 5. The fifth goal is to identify and address the hypercoagulability phase seen in many hospitalized COVID-19 patients. Patients who would benefit from anticoagulation therapy can be identified by a marked increase in d-dimer and prothrombin time with a decrease in fibrinogen. To correct this disseminated intravascular coagulation-like phase, anticoagulation therapy with low molecular weight heparin is preferred. Anticoagulation therapy with unfractionated heparin is preferred in COVID-19 patients with acute kidney injuries. 6. The last goal is prophylaxis for persons who are not yet infected. Potential supplements include vitamin D and zinc. Although the data for such supplements is not extremely strong, it can be argued that almost 50% of the population worldwide has a vitamin D deficiency. Correcting this deficiency would be beneficial regardless of any impact of COVID-19. Similarly, zinc is an important supplement that is important in one's diet regardless of any effect on SARS-CoV-2. As emerging therapies are found to be more effective against the SARS-CoV-2 pathogenic mechanisms identified, they can be substituted for those therapies presented in this review.
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COVID-19/fisiopatología , COVID-19/terapia , Pulmón/patología , SARS-CoV-2/patogenicidad , Antivirales/uso terapéutico , COVID-19/complicaciones , Humanos , Hipoxia/prevención & control , Inflamación/tratamiento farmacológico , Carga Viral/efectos de los fármacosRESUMEN
BACKGROUND AND AIMS: The ribosomal DNA (rDNA) gene family, encoding ribosomal RNA (rRNA), has long been regarded as an archetypal example illustrating the model of concerted evolution. However, controversy is arising, as rDNA in many eukaryotic species has been proved to be polymorphic. Here, a metagenomic strategy was applied to detect the intragenomic polymorphism as well as the evolutionary patterns of 26S rDNA across the genus Camellia. METHODS: Degenerate primer pairs were designed to amplify the 26S rDNA fragments from different Camellia species. The amplicons were then paired-end sequenced on the Illumina MiSeq platform. KEY RESULTS: An extremely high level of rDNA polymorphism existed universally in Camellia. However, functional rDNA was still the major component of the family, and was relatively conserved among different Camellia species. Sequence variations mainly came from rRNA pseudogenes and favoured regions that are rich in GC. Specifically, some rRNA pseudogenes have existed in the genome for a long time, and have even experienced several expansion events, which has greatly enriched the abundance of rDNA polymorphism. CONCLUSIONS: Camellia represents a group in which rDNA is subjected to a mixture of concerted and birth-and-death evolution. Some rRNA pseudogenes may still have potential functions. Conversely, when released from selection constraint, they can evolve in the direction of decreasing GC content and structural stability through a methylation-induced process, and finally be eliminated from the genome.
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Camellia , Evolución Molecular , ADN Ribosómico , Filogenia , Seudogenes , ARN RibosómicoRESUMEN
In the present study, we analysed the effects of SNP rs174547 (T/C) in the fatty acid desaturase 1 (FADS1) gene on long-chain PUFA levels. Four databases were searched to retrieve related literature with keywords such as fatty acid (FA), SNP, FADS1 and rs174547. A meta-analysis of the data was performed using Stata12.0 software, including summary statistics, test for heterogeneity, evaluation of publication bias, subgroup analysis and sensitivity analysis. The associations between rs174547 in FADS1 and seven types of FA, and Δ-5 (D5D) and Δ-6 fatty acid desaturase (D6D) activity were assessed based on the pooled results from eleven papers. A total of 3713 individuals (1529 TT and 2184 TC + CC) were included. The results demonstrated that minor C allele carriers of rs174547 had higher linoleic acid (LA; P < 0·001) and α-linolenic acid (P = 0·020) levels, lower γ-linolenic acid (GLA; P = 0·001) and arachidonic acid (P = 0·024) levels, and lower D5D (P = 0·005) and D6D (P = 0·004) activities than the TT genotype group. Stratification analysis showed that minor C allele carriers of rs174547 had higher LA and lower GLA levels and lower D6D activities in plasma (LA, P < 0·001; GLA, P < 0·001; D6D activity, P < 0·001) samples and in Asian populations (LA, P < 0·001; GLA, P = 0·001; D6D activity, P = 0·001) than the TT genotype group. In conclusion, minor C allele carriers of the SNP rs174547 were associated with decreased activity of D5D and D6D.
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delta-5 Desaturasa de Ácido Graso/genética , Ácidos Grasos Insaturados/sangre , Polimorfismo de Nucleótido Simple , Alelos , Ácido Araquidónico , Humanos , Ácido Linoleico , Ácido alfa-Linolénico , Ácido gammalinolénicoRESUMEN
Respiratory viral infections are associated with a wide range of acute syndromes and infectious disease processes in children and adults worldwide. Many viruses are implicated in these infections, and these viruses are spread largely via respiratory means between humans but also occasionally from animals to humans. This article is an American Society for Microbiology (ASM)-sponsored Practical Guidance for Clinical Microbiology (PGCM) document identifying best practices for diagnosis and characterization of viruses that cause acute respiratory infections and replaces the most recent prior version of the ASM-sponsored Cumitech 21 document, Laboratory Diagnosis of Viral Respiratory Disease, published in 1986. The scope of the original document was quite broad, with an emphasis on clinical diagnosis of a wide variety of infectious agents and laboratory focus on antigen detection and viral culture. The new PGCM document is designed to be used by laboratorians in a wide variety of diagnostic and public health microbiology/virology laboratory settings worldwide. The article provides guidance to a rapidly changing field of diagnostics and outlines the epidemiology and clinical impact of acute respiratory viral infections, including preferred methods of specimen collection and current methods for diagnosis and characterization of viral pathogens causing acute respiratory tract infections. Compared to the case in 1986, molecular techniques are now the preferred diagnostic approaches for the detection of acute respiratory viruses, and they allow for automation, high-throughput workflows, and near-patient testing. These changes require quality assurance programs to prevent laboratory contamination as well as strong preanalytical screening approaches to utilize laboratory resources appropriately. Appropriate guidance from laboratorians to stakeholders will allow for appropriate specimen collection, as well as correct test ordering that will quickly identify highly transmissible emerging pathogens.
Asunto(s)
Técnicas de Laboratorio Clínico/métodos , Técnicas Microbiológicas/métodos , Técnicas de Diagnóstico Molecular , Infecciones del Sistema Respiratorio/diagnóstico , Virología/métodos , Virosis/diagnóstico , Enfermedad Aguda , Técnicas de Laboratorio Clínico/normas , Humanos , Técnicas Microbiológicas/normas , Técnicas de Diagnóstico Molecular/normas , Técnicas de Diagnóstico Molecular/tendencias , Infecciones del Sistema Respiratorio/virología , Virología/normas , Virosis/virologíaRESUMEN
An automated on-line solid-phase extraction (SPE) combined with LC-MS/MS method was developed for determination of deoxynivalenol (DON), 3-acetyl-DON and 15-acetyl-DON in corn flour and wheat flour samples. The extraction solvent of the samples was injected into the automated on-line SPE system to remove matrix interference. After washing step, the targets were eluted from the SPE cartridge into liquid chromatography (LC) column. Several SPE parameters including injection volume, elution volume and eluting flow rate were assessed and optimized. Method validation was evaluated and good linearity was obtained (R2 > 99%) with the limit of detection of 0.1-0.2 µg/kg. Recoveries were evaluated in spiked corn flour and wheat flour samples at three concentrations and the values ranged from 86.5% to 99.7%. The benefit of the present method with automated on-line SPE system is the ability to inject directly pure extracts into LC-MS/MS, offering faster analyses and improving analysis efficiency.
Asunto(s)
Harina , Espectrometría de Masas en Tándem , Cromatografía Liquida , Harina/análisis , Extracción en Fase Sólida , Tricotecenos , Triticum , Zea maysRESUMEN
The COVID-19 outbreak has had a major impact on clinical microbiology laboratories in the past several months. This commentary covers current issues and challenges for the laboratory diagnosis of infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the preanalytical stage, collecting the proper respiratory tract specimen at the right time from the right anatomic site is essential for a prompt and accurate molecular diagnosis of COVID-19. Appropriate measures are required to keep laboratory staff safe while producing reliable test results. In the analytic stage, real-time reverse transcription-PCR (RT-PCR) assays remain the molecular test of choice for the etiologic diagnosis of SARS-CoV-2 infection while antibody-based techniques are being introduced as supplemental tools. In the postanalytical stage, testing results should be carefully interpreted using both molecular and serological findings. Finally, random-access, integrated devices available at the point of care with scalable capacities will facilitate the rapid and accurate diagnosis and monitoring of SARS-CoV-2 infections and greatly assist in the control of this outbreak.