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1.
J Clin Invest ; 2021 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-33529172

RESUMEN

BACKGROUND: Immunization with replication-competent recombinant vectors provides exposure to transgene-encoded antigens in the context of inflammation that may drive more potent and durable immunity compared to non-replicating vaccines. To understand the features of a replicating vaccine that drive such responses we tested a replication-competent adenovirus type 4 encoding influenza virus H5 hemagglutinin (Ad4-H5-Vtn) administered by an oral capsule or via a tonsillar swab or nasal spray. METHODS: Viral shedding from the nose, mouth, and rectum was measured by PCR and culture. H5-specific IgG and IgA antibodies were measured by bead array binding assays. Serum antibodies were measured by a pseudovirus entry inhibition assay (PVEI), microneutralization (MN), and hemagglutinin inhibition (HAI). RESULTS: Ad4-H5-Vtn DNA was shed from most upper respiratory tract (URT)-immunized volunteers for 2-4 weeks, but cultured from only 60% of participants with a median duration of one day. Ad4-H5-Vtn vaccination induced increases in H5-specific CD4+ and CD8+ T cells in the peripheral blood and IgG and IgA in nasal, cervical and rectal secretions. URT immunizations induced high levels of serum neutralizing antibodies (NAb) to H5 which remained stable at week 26. The duration of viral shedding correlated with the magnitude of the NAb response at week 26. Adverse events (AE) were mild, and peak NAb titer was associated with overall AE frequency or duration. Serum neutralizing antibody titers could be boosted to very high levels 2-5 years after Ad4-H5-Vtn vaccination with recombinant H5 or inactivated split H5N1 vaccine. CONCLUSION: Replicating Ad4 delivered to the URT causes prolonged exposure to antigen, drives durable systemic and mucosal immunity, and is a promising platform for the induction of immunity against viral surface glycoprotein targets. TRIAL REGISTRATION: ClinicalTrials.gov NCT01443936, NCT01806909. FUNDING: Intramural and Extramural Research Programs of the NIAID, NIH; and the Centers of Influenza Virus Research and SurveillanceFunding. Intramural and Extramural Research Programs of the NIAID, NIH; and the Centers of Influenza Virus Research and Surveillance.

2.
Radiography (Lond) ; 2021 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-33581989

RESUMEN

INTRODUCTION: The updated National Institute of Clinical Excellence (NICE) guidelines of 2017 state that new generation cardiac CT scanners (Aquilion ONE, Brilliance iCT, Discovery CT750 HD and Somatom Definition Flash) are recommended as an option for first-line imaging of the coronary arteries in people with suspected stable coronary artery disease (with an estimated likelihood of coronary artery disease of 10-29%) in whom imaging with earlier generation CT scanners is difficult. New generation cardiac CT scanners are also recommended as an option for first-line evaluation of disease progression, to establish need for revascularisation in people with known coronary artery disease in whom imaging with earlier generation CT scanners is difficult. CT scanning might not be necessary in situations in which immediate revascularisation is being considered. The European Society of Cardiology 2019 clinical practice guidelines recommend non-invasive functional imaging for myocardial ischaemia or coronary CT angiography (CTA) as the initial test to diagnose CAD in symptomatic patients in whom obstructive CAD cannot be excluded by clinical assessment alone. Given increased computed tomography coronary angiogram (CTCA) utilisation, radiation dose, contrast enhancement and image quality of prospective ECG-gated CTCA between 256-slice single-source and 192x2-slice dual-source CT scanners were retrospectively evaluated. METHODS: Prospectively gated CTCA data from 63 patients on a 256-slice CT (group A) and 71 patients on a 192x2-slice dual source CT (group B) from January to December 2016 were retrospectively evaluated respectively. Scanner-reported dose length product values were used with a conversion factor (k = 0.014 mSv/mGy x cm) to estimate effective dose. Contrast enhancement was assessed with mean CT attenuation at selected regions of interest on axial coronary images. Image quality of the coronary arteries was assessed by a 4-point grading score (1 = non-diagnostic, 4 = excellent image quality). RESULTS: The radiation doses in group B were significantly lower than group A (3.68 + 2.13 mSv versus 4.81 + 1.56 mSv, p < 0.001). There were no significant differences in contrast enhancement in the left coronary artery, proximal right coronary artery and left ventricular wall for both groups. Vessel image quality scores for group B were higher than group A (right coronary artery (RCA): 3.2 + 0.7 versus 2.4 + 0.7, p < 0.001; left anterior descending (LAD) artery: 3.0 + 0.8 vs 2.5 + 0.6, p < 0.001; left circumflex (LCx) artery: 3.3 + 0.7 vs 2.6 + 0.6, p < 0.001). Coronary artery contour scores for group B were significantly higher than group A (RCA: 3.2 + 0.8 versus 2.3 + 0.7, p < 0.001; LAD: 3.0 + 0.7 versus 2.4 + 0.6, p < 0.001; LCx: 3.3 + 0.6 versus 2.5 + 0.6, p < 0.001). CONCLUSION: Prospective ECG-gated CTCA performed on 192x2-slice CT results in better image quality and lower radiation dose than 256-slice CT. There were no significant differences in contrast enhancement in left main coronary artery (LMCA), proximal RCA and left ventricular wall in both groups. IMPLICATIONS FOR PRACTICE: In institutions with both 256-slice and 192x2-slice CT scanners, we recommend that CTCAs be preferentially performed using the 192x2-slice CT scanner.

3.
Clin Transl Oncol ; 2021 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-33625672

RESUMEN

BACKGROUND: The study examines the function of hypoxia-mediated down-regulation of microRNAs (miRNAs) (mir-30c, mir-135a, and mir-27a) in the process of bladder cancer immune escape. METHODS: Quantitative Real-time PCR (qRT-PCR) was carried out to determine gene expression levels of Drosha and Dicer under hypoxia treatment, while western blotting and flow cytometry were used to determine protein expression. Seven reported miRNAs were identified via qRT-PCR assay. Flow cytometry detection of CD3/CD4/CD8-positive expression and statistics. Enzyme-linked immunosorbent assay (ELISA) detected cellular immune factors content. Cell apoptosis was checked via flow cytometry assay. Luciferase report assay and western blot assays were both used to verify the relationship between miRNAs and Casitas B-lineage lymphoma proto-oncogene b (Cbl-b). The animal model was established and Hematoxylin-eosin (HE) staining, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, and immunohistochemistry (IHC) assays were separately used to verify the conclusions. RESULTS: The CD3 + /CD4 + expression was increased in the hypoxia group, while CD3 + /CD8 + expression, the cellular immune factors content Interleukin-2 (IL-2) and Tumor Necrosis Factor-α (TNFα) along with the cell apoptosis were suppressed. The protein expression of Cbl-b was found to be up-regulated in the hypoxia group. After constructing the overexpression/ knockdown of Cbl-b in peripheral blood mononuclear cell (PBMC), Cbl-b has been found to promote tumor immune escape in bladder cancer. Furthermore, Cbl-b had been identified as the co-targets of mir-30c, mir-135a, and mir-27a and down-regulation of miRNA biogenesis promotes Cbl-b expression and deactivating T cells in vitro/in vivo. CONCLUSION: Hypoxia-mediated down-regulation of miRNAs' biogenesis promotes tumor immune escape in bladder cancer, which could bring much more advance to the medical research on tumors.

4.
Zhonghua Xue Ye Xue Za Zhi ; 41(10): 836-842, 2020 Oct 14.
Artículo en Chino | MEDLINE | ID: mdl-33190441

RESUMEN

Objective: Endoplasmic reticulum stress(ERS)was used as the research emphasis to further investigate the mechanisms of apoptosis of FLT3-ITD-mutated leukemia cells and decreased expression of FLT3-ITD mutated protein induced by all-trans retinoic acid(ATRA). Methods: FLT3-ITD-mutated leukemia cell lines(MV4-11 and MOLM13)were treated with ATRA. Flow cytometry was conducted to assess cell apoptosis. Real-time fluorescent quantitative PCR(RT-qPCR)and Western blot were used to detect the expression of ERS-related and autophagy-related genes and protein, respectively. Results: A low-dose ATRA further increased FLT3-ITD cells and ERS levels. ATRA acted on the ERS-related PERK/eif2ɑ signaling pathway and continued to increase the ERS of FLT3-ITD cells, resulting in an upregulation of apoptotic gene CHOP expression. After the treatment with ATRA, FLT3-ITD protein in FLT3-ITD cells was decreased. Of the two main ERS-related protein degradation pathways, ER-associated degradation(ERAD)and ER-activated autophagy(ERAA), the expression of ERAD-related protein ATF6 in FLT3-ITD cells was not significantly changed on ATRA, whereas the expression of ERAA-related proteins Atg7 and Atg5 were significantly increased. Conclusions: ATRA further raises the ERS level of FLT3-ITD cells continuously by activating the ERS-related PERK/eif2ɑ signal pathway and induces FLT3-ITD protein autophagy degradation through ERAA pathway, which induces apoptosis of FLT3-ITD-mutated leukemia cells. These results provide preliminary evidence on the use of ATRA in the treatment of refractory leukemia with FLT3-ITD.

5.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 55(11): 891-896, 2020 Nov 09.
Artículo en Chino | MEDLINE | ID: mdl-33171564

RESUMEN

Objective: To evaluate the clinical outcomes of digital technique-aided occlusal rehabilitation based on implant-supported fixed prostheses (ISFP), and to provide some information for clinical application of digital technique. Methods: Retrospectively reviewed the cases which had used neuromuscular system and condylar movement tracing device to reconstruct occlusion in one or double jaw fully edentulous ISFP from January, 2013 to January, 2020. A total of 6 eligible patients were enrolled in the present study with 56 implants and 8 ISFP, including 4 male patients and 2 female patients, aged from 43 to 74 years. The clinical outcomes were evaluated in four aspects, including implant survival rate, implants success rate, marginal bone loss and the occurrence of prosthesis complications. Results: The follow-up time was (4.0±2.2) years (1-7 years). The implant survival rate was 100% (56/56) and the implant success rate was 98% (55/56), with an average missal and distal marginal bone loss of (0.04±0.11) mm/year. Veneer chipping occurred at incisal edge of 2 adjacent incisors in only one prosthesis 3 years after rehabilitation. Conclusions: Combination of digital techniques of neuromuscular system and condylar movement tracing device to assist occlusal rehabilitation based on ISFP showed a high implant success rate. The complication seldom happened. Long and stable occlusion has been observed. The clinical outcomes were favorable.


Asunto(s)
Implantes Dentales , Arcada Edéntula , Boca Edéntula , Adulto , Anciano , Implantación Dental Endoósea , Diseño de Prótesis Dental , Prótesis Dental de Soporte Implantado , Fracaso de la Restauración Dental , Femenino , Estudios de Seguimiento , Humanos , Arcada Edéntula/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
7.
J Nutr Health Aging ; 24(9): 951-958, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33155620

RESUMEN

OBJECTIVES: To elucidate the hypothetically different interactions between delirium and post-discharge prognostic indicators in elderly hospital inpatients with versus without dementia. DESIGN: Retrospective cohort study of claims data by Taiwan National Health Insurance beneficiaries between 2002-2013. SETTING: Records of public hospital admissions in the Taiwan National Health Insurance Research database. PARTICIPANTS: Propensity-score matched subgroups of patients with delirium superimposed on dementia (n = 922) versus dementia alone (n = 922), delirium alone (n = 680) versus neither delirium nor dementia (n = 680). MEASUREMENTS: Mortality, emergency department visits, readmissions, and psychotropic drug use, within 30, 180, and 365 days of discharge, were analyzed using multivariate proportional hazards or logistic regression analyses. RESULTS: Delirium superimposed on dementia was not associated with increased post-discharge mortality, or emergency department visits, but significantly increased the risk of readmissions at 365-day follow-up (adjusted HR, 95% CI: 1.26, 1.01-1.56). However, delirium without dementia was significantly associated with increased post-discharge mortality, emergency department visits and readmissions at 180 days and 365 days (respective adjusted HRs: mortality, 1.63 and 1.79; adjusted ORs: emergency department visits, 1.89 and 1.81; readmissions, 1.47 and 1.53). Delirium in patients both with dementia and without, was associated with six-fold higher likelihood of in-hospital psychotropic drug use, and doubled post-discharge psychotropic drug usage. CONCLUSIONS: The obvious association between in-hospital delirium and worsened long-term prognosis, irrespective of dementia, raises awareness to warrants proactive and multimodal prevention and intervention strategies. Furthermore, the mechanisms about different influence of delirium for patients with/without dementia need to be further explored.

8.
Beijing Da Xue Xue Bao Yi Xue Ban ; 52(5): 803-808, 2020 Oct 18.
Artículo en Chino | MEDLINE | ID: mdl-33047711

RESUMEN

OBJECTIVE: To determine the environmental contamination degree of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in corona virus disease 2019 (COVID-19) wards, to offer gui-dance for the infection control and to improve safety practices for medical staff, by sampling and detecting SARS-CoV-2 nucleic acid from the air of hospital wards, the high-frequency contact surfaces in the contaminated area and the surfaces of medical staff's protective equipment in a COVID-19 designated hospital in Wuhan, China. METHODS: From March 11 to March 19, 2020, we collected air samples from the clean area, the buffer room and the contaminated area respectively in the COVID-19 wards using a portable bioaerosol concentrator WA-15. And sterile premoistened swabs were used to sample the high-frequency contacted surfaces in the contaminated area and the surfaces of medical staff's protective equipment including outermost gloves, tracheotomy operator's positive pressure respiratory protective hood and isolation clothing. The SARS-CoV-2 nucleic acid of the samples were detected by real-time fluorescence quantitative PCR. During the isolation medical observation period, those medical staff who worked in the COVID-19 wards were detected for SARS-CoV-2 nucleic acid with oropharyngeal swabs, IgM and IgG antibody in the sera, and chest CT scans to confirm the infection status of COVID-19. RESULTS: No SARS-CoV-2 nucleic acid was detected in the tested samples, including the 90 air samples from the COVID-19 wards including clean area, buffer room and contaminated area, the 38 high-frequency contact surfaces samples of the contaminated area and 16 surface samples of medical staff's protective equipment including outermost gloves and isolation clothing. Moreover, detection of SARS-CoV-2 nucleic acid by oropharyngeal swabs and IgM, IgG antibodies in the sera of all the health-care workers who participated in the treatment for COVID-19 were all negative. Besides, no chest CT scan images of medical staff exhibited COVID-19 lung presentations. CONCLUSION: Good ventilation conditions, strict disinfection of environmental facilities in hospital wards, guidance for correct habits in patients, and strict hand hygiene during medical staff are important to reduce the formation of viral aerosols, cut down the aerosol load, and avoid cross-infection in isolation wards. In the face of infectious diseases that were not fully mastered but ma-naged as class A, it is safe for medical personnel to be equipped at a high level.


Asunto(s)
Infecciones por Coronavirus , Pandemias , Neumonía Viral , Síndrome Respiratorio Agudo Grave , Betacoronavirus , China , Humanos , Cuerpo Médico , Equipos de Seguridad , Síndrome Respiratorio Agudo Grave/diagnóstico , Síndrome Respiratorio Agudo Grave/prevención & control
9.
J Virol ; 94(23)2020 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-32907983

RESUMEN

In various infections or vaccinations of mice or humans, reports of the persistence and the requirements for restimulation of the cytotoxic mediators granzyme B (GrB) and perforin (PRF) in CD8+ T cells have yielded disparate results. In this study, we examined the kinetics of PRF and GrB mRNA and protein expression after stimulation and associated changes in cytotoxic capacity in virus-specific memory cells in detail. In patients with controlled HIV or cleared respiratory syncytial virus (RSV) or influenza virus infections, all virus-specific CD8+ T cells expressed low PRF levels without restimulation. Following stimulation, they displayed similarly delayed kinetics for lytic protein expression, with significant increases occurring by days 1 to 3 before peaking on days 4 to 6. These increases were strongly correlated with, but were not dependent upon, proliferation. Incremental changes in PRF and GrB percent expression and mean fluorescence intensity (MFI) were highly correlated with increases in HIV-specific cytotoxicity. mRNA levels in HIV-specific CD8+ T-cells exhibited delayed kinetics after stimulation as with protein expression, peaking on day 5. In contrast to GrB, PRF mRNA transcripts were little changed over 5 days of stimulation (94-fold versus 2.8-fold, respectively), consistent with posttranscriptional regulation. Changes in expression of some microRNAs, including miR-17, miR-150, and miR-155, suggested that microRNAs might play a significant role in regulation of PRF expression. Therefore, under conditions of extremely low or absent antigen levels, memory virus-specific CD8+ T cells require prolonged stimulation over days to achieve maximal lytic protein expression and cytotoxic capacity.IMPORTANCE Antigen-specific CD8+ T cells play a major role in controlling most virus infections, primarily by perforin (PRF)- and granzyme B (GrB)-mediated apoptosis. There is considerable controversy regarding whether PRF is constitutively expressed, rapidly increased similarly to a cytokine, or delayed in its expression with more prolonged stimulation in virus-specific memory CD8+ T cells. In this study, the degree of cytotoxic capacity of virus-specific memory CD8+ T cells was directly proportional to the content of lytic molecules, which required antigenic stimulation over several days for maximal levels. This appeared to be modulated by increases in GrB transcription and microRNA-mediated posttranscriptional regulation of PRF expression. Clarifying the requirements for maximal cytotoxic capacity is critical to understanding how viral clearance might be mediated by memory cells and what functions should be induced by vaccines and immunotherapies.

10.
Eur Rev Med Pharmacol Sci ; 24(14): 7575, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32744680

RESUMEN

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "The effect of miR-224 down-regulation on SW80 cell proliferation and apoptosis and weakening of ADM drug resistance, by C.-Q. Liang, Y.-M. Fu, Z.-Y. Liu, B.-R. Xing, Y. Jin, J.-L. Huang, published in Eur Rev Med Pharmacol Sci 2017; 21 (21): 5008-5016-PMID: 29164556" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/13747.

11.
Zhonghua Yan Ke Za Zhi ; 56(8): 593-599, 2020 Aug 11.
Artículo en Chino | MEDLINE | ID: mdl-32847334

RESUMEN

Objective: To investigate the prevalence, causes and risk factors of moderate or severe visual impairment and blindness in people with type 2 diabetes over 50 years old in Funing County, Yancheng. Methods: This is a cross-sectional study. Using cluster random sampling, 84 survey sites were selected, and eye examination was performed on people with type 2 diabetes over 50 years old who were registered with the chronic disease information center of Funing County Center for Disease Control and Prevention in Yancheng, Jiangsu. The prevalence of moderate or severe visual impairment and blindness were calculated by different ages and genders. The causes of blindness and visual impairment were determined, and their influencing factors were analyzed by univariate and multivarite logistic regression. Results: A total of 2 067 people were investigated in this study, and 1 909 people were included. The response rate was 92.4%. Based on PVA, the prevalence of blindness and moderate to severe visual impairment was 5.29% (95%CI: 4.29%-6.30%) and 18.54% (95%CI: 16.80%-20.29%). The prevalence of blindness was related to age, marital status, education, duration of diabetes, history of diabetic nephropathy, systolic blood pressure and nuclear opacity. The prevalence of moderate or severe visual impairment was related to age, gender, educational level, diabetes treatment, exercise, and glycated hemoglobin. The prevalence of blindness and moderate to severe visual impairment was 3.67% (95%CI: 2.82%-4.51%) and 9.80% (95%CI: 8.46%-11.13%) based on BCVA. The prevalence of blindness was related to age, marital status, education, duration of diabetes, history of diabetic nephropathy, exercise and systolic blood pressure, while the prevalence of moderate or severe visual impairment was related to age, educational level, diabetes treatment and nuclear opacity. The primary cause of blindness and visual impairment is cataract, followed by diabetic retinopathy. Conclusions: The prevalence of moderate or severe visual impairment and blindness in people with type 2 diabetes in Funing County is relatively high. Attention should be paid to the prevention of blindness in this population. (Chin J Ophthalmol, 2020, 56: 593-599).


Asunto(s)
Catarata , Diabetes Mellitus Tipo 2/complicaciones , Baja Visión/epidemiología , Ceguera/etiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Encuestas y Cuestionarios , Trastornos de la Visión/epidemiología
12.
J Endocrinol Invest ; 2020 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-32729050

RESUMEN

PURPOSE: Primary hyperparathyroidism has deleterious effects on health and causes nephrolithiasis and osteoporosis. However, it remains unclear whether parathyroidectomy benefits kidney function among patients with primary hyperparathyroidism. METHODS: In this retrospective study, patients with primary hyperparathyroidism receiving parathyroidectomy in a tertiary medical center between 2003 and 2017 were followed up until December 31 2017, death, or requiring renal replacement therapy. Impact of parathyroidectomy on kidney function was examined using longitudinal estimated glomerular filtration rate (eGFR) change scales: single, average, absolute difference, percent change, annual decline rate, and slope. We applied linear mixed-effect model to determine the effect of parathyroidectomy on kidney function. RESULTS: During study period, 167 patients with primary hyperparathyroidism were identified from 498 parathyroidectomized patients, and finally, 27 patients fulfilled our stringent criteria. Median follow-up duration was 1.50 years (interquartile range 1.05-1.81) before surgery and 2.47 years (1.37-6.43) after surgery. Although parathyroidectomy did not affect amount of proteinuria and distribution of eGFR, parathyroidectomy significantly slowed decline rate of eGFR compared with that before surgery (- 1.67 versus - 2.73 mL/min/1.73 m2/year, p < 0.001). More importantly, parathyroidectomy made more beneficial effects on kidney function in patients with age < 65 years and those without chronic kidney disease or hypertension. CONCLUSIONS: Our study showed that parathyroidectomy slows renal function decline irrespective of age or comorbidities, which offers novel insight into the revision of guidelines for surgical indications in primary hyperparathyroidism. Given small sample size, further large-scale controlled studies are warranted to confirm our findings.

13.
Rhinology ; 2020 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-32720938

RESUMEN

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a rare tumor with highly recurrent and lack of effective treatment. Long non- coding RNAs (lncRNAs) have been reported to play roles in various cancers including NPC. METHODS: In the current study, two cell lines of NPC (CNE-2Z and 5-8F cells) were transfected with short hairpin RNA (shRNA) targeting lncRNA-ENST00000412010 (shlncRNA) or control shRNA (shControl). Cell proliferation, survival, in vitro colony formation, and in vivo xenograft tumor formation were then investigated. RESULTS: The study found that cells transfected with shlncRNA grew significantly slower than the cells transfected with shControl as measured on day 5; increased in Annexin V expression; decreased in colony formation; and smaller in xenograft tumor size on day 45. Expression of DNA damage-inducible transcript 3, dual specificity protein phosphatase 5, insulin receptor substrate 1, interleukin-6, and tribbles homolog 3 genes was significantly up-regulated in the cells transfected with shlncRNA, while gene expression of matrix metalloproteinase-7 and cyclin-dependent kinase 4 inhibitor B was significantly down-regulated in the cells transfected with shlncRNA. Immunoblotting assay confirmed DUSP5 protein was significantly increased while proteins of MMP-7 and CDKN2B were significantly lower in the cells lacking lncRNA than that of the control cells. CONCLUSIONS: These findings suggested that lncRNA-ENST00000412010 plays a role in modulating NPC survival and tumorigenesis through regulating molecules associated with cell cycle and protein phosphatase.

14.
Artículo en Inglés | MEDLINE | ID: mdl-32666619

RESUMEN

BACKGROUND: Severe acute respiratory infection (SARI) accounts for a large burden of illness in Indonesia. However, epidemiology of SARI in tertiary hospitals in Indonesia is unknown. This study sought to assess the burden, clinical characteristics, and etiologies of SARI and concordance of clinical diagnosis with confirmed etiology. METHODS: Data and samples were collected from subjects presenting with SARI as part of the acute febrile Illness requiring hospitalization study (AFIRE). In tertiary hospitals, clinical diagnosis was ascertained from chart review. Samples were analyzed to determine the "true" etiology of SARI at hospitals and Indonesia Research Partnership on Infectious Diseases (INA-RESPOND) laboratory. Distribution and characteristics of SARI by true etiology and accuracy of clinical diagnosis were assessed. RESULTS: Four hundred and twenty of 1464 AFIRE subjects presented with SARI; etiology was identified in 242 (57.6%), including 121 (28.8%) viruses and bacteria associated with systemic infections, 70 (16.7%) respiratory bacteria and viruses other than influenza virus, and 51 (12.1%) influenza virus cases. None of these influenza patients were accurately diagnosed as having influenza during hospitalization. CONCLUSIONS: Influenza was misdiagnosed among all patients presenting with SARI to Indonesian tertiary hospitals in the AFIRE study. Diagnostic approaches and empiric management should be guided by known epidemiology. Public health strategies to address the high burden of influenza should include broad implementation of SARI screening, vaccination programs, clinician education and awareness campaigns, improved diagnostic capacity, and support for effective point-of-care tests.

15.
J Am Med Inform Assoc ; 27(7): 1028-1036, 2020 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-32626900

RESUMEN

OBJECTIVE: We developed and evaluated a privacy-preserving One-shot Distributed Algorithm to fit a multicenter Cox proportional hazards model (ODAC) without sharing patient-level information across sites. MATERIALS AND METHODS: Using patient-level data from a single site combined with only aggregated information from other sites, we constructed a surrogate likelihood function, approximating the Cox partial likelihood function obtained using patient-level data from all sites. By maximizing the surrogate likelihood function, each site obtained a local estimate of the model parameter, and the ODAC estimator was constructed as a weighted average of all the local estimates. We evaluated the performance of ODAC with (1) a simulation study and (2) a real-world use case study using 4 datasets from the Observational Health Data Sciences and Informatics network. RESULTS: On the one hand, our simulation study showed that ODAC provided estimates nearly the same as the estimator obtained by analyzing, in a single dataset, the combined patient-level data from all sites (ie, the pooled estimator). The relative bias was <0.1% across all scenarios. The accuracy of ODAC remained high across different sample sizes and event rates. On the other hand, the meta-analysis estimator, which was obtained by the inverse variance weighted average of the site-specific estimates, had substantial bias when the event rate is <5%, with the relative bias reaching 20% when the event rate is 1%. In the Observational Health Data Sciences and Informatics network application, the ODAC estimates have a relative bias <5% for 15 out of 16 log hazard ratios, whereas the meta-analysis estimates had substantially higher bias than ODAC. CONCLUSIONS: ODAC is a privacy-preserving and noniterative method for implementing time-to-event analyses across multiple sites. It provides estimates on par with the pooled estimator and substantially outperforms the meta-analysis estimator when the event is uncommon, making it extremely suitable for studying rare events and diseases in a distributed manner.

16.
Zhonghua Gan Zang Bing Za Zhi ; 28(5): 428-433, 2020 May 20.
Artículo en Chino | MEDLINE | ID: mdl-32536060

RESUMEN

Objective: To investigate the mutation characteristics and clinical relevance of Gilbert syndrome (GS) and Crigler-Najjar syndrome (CNS) in relation to uridine diphosphate glucuronosyltransferase A1 (UGT1A1) gene. Methods: The characteristics of UGT1A1 gene mutation and their clinical relevance were analyzed by searching PubMed and Human Gene Mutation Databases. Results: A total of 163 mutation sites were found in the UGT1A1 gene since November 16, 2018. The following patterns existed at the above sites: (1) the numbers of gene mutations occurring between different exons of UGT1A1 was related to GS or CNS phenotypes, and were positively correlated with the length of the exon; (2) nonsense point mutations was mainly occurred in type I of CNS; (3) GS, Crigler-Najjar syndrome type II compound heterozygous mutation sites had a certain combination and distribution, among which - 3279t > G mutation was found in all four GS complex heterozygous compositions; (4) UGT1A1 gene mutation sites reported in Asia had marked aggregation in c.211-c.558. Conclusion: UGT1A1 gene mutation characteristics and clinical relevance varies with different mutation sites, reporting areas and populations. This study has reference value for basic research and clinical diagnosis and treatment of GS and CNS.


Asunto(s)
Síndrome de Crigler-Najjar , Enfermedad de Gilbert , Glucuronosiltransferasa , Mutación , Cardiomiopatías , Síndrome de Crigler-Najjar/genética , Genitales/anomalías , Enfermedad de Gilbert/genética , Glucuronosiltransferasa/genética , Humanos , Uridina , Uridina Difosfato
17.
BMC Infect Dis ; 20(1): 364, 2020 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-32448167

RESUMEN

BACKGROUND: Reports of human rickettsial infection in Indonesia are limited. This study sought to characterize the epidemiology of human rickettsioses amongst patients hospitalized with fever at 8 tertiary hospitals in Indonesia. METHODS: Acute and convalescent blood from 975 hospitalized non-dengue patients was tested for Rickettsia IgM and IgG by ELISA. Specimens from cases with seroconversion or increasing IgM and/or IgG titers were tested for Rickettsia IgM and IgG by IFA and Rickettsia genomes using primers for Rickettsia (R.) sp, R. typhi, and Orientia tsutsugamushi. Testing was performed retrospectively on stored specimens; results did not inform patient management. RESULTS: R. typhi, R. rickettsii, and O. tsutsugamushi IgG antibodies were identified in 269/872 (30.8%), 36/634 (5.7%), and 19/504 (3.8%) of samples, respectively. For the 103/975 (10.6%) non-dengue patients diagnosed with acute rickettsial infection, presenting symptoms included nausea (72%), headache (69%), vomiting (43%), lethargy (33%), anorexia (32%), arthralgia (30%), myalgia (28%), chills (28%), epigastric pain (28%), and rash (17%). No acute rickettsioses cases were suspected during hospitalization. Discharge diagnoses included typhoid fever (44), dengue fever (20), respiratory infections (7), leptospirosis (6), unknown fever (6), sepsis (5), hepatobiliary infections (3), UTI (3), and others (9). Fatalities occurred in 7 (6.8%) patients, mostly with co-morbidities. CONCLUSIONS: Rickettsial infections are consistently misdiagnosed, often as leptospirosis, dengue, or Salmonella typhi infection. Clinicians should include rickettsioses in their differential diagnosis of fever to guide empiric management; laboratories should support evaluation for rickettsial etiologies; and public policy should be implemented to reduce burden of disease.


Asunto(s)
Fiebre/diagnóstico , Hospitalización , Infecciones por Rickettsia/diagnóstico , Infecciones por Rickettsia/epidemiología , Rickettsia rickettsii/inmunología , Rickettsia typhi/inmunología , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anticuerpos Antibacterianos/sangre , Niño , Preescolar , Dengue/diagnóstico , Diagnóstico Diferencial , Ensayo de Inmunoadsorción Enzimática , Femenino , Fiebre/microbiología , Humanos , Inmunoglobulina G/sangre , Indonesia/epidemiología , Lactante , Leptospirosis/diagnóstico , Masculino , Persona de Mediana Edad , Orientia tsutsugamushi/inmunología , Estudios Retrospectivos , Infecciones por Rickettsia/microbiología , Tifus por Ácaros/diagnóstico , Fiebre Tifoidea/diagnóstico , Adulto Joven
18.
Exp Neurol ; 329: 113319, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32305418

RESUMEN

Heterozygous mutations in the X-linked gene CASK are associated with intellectual disability, microcephaly, pontocerebellar hypoplasia, optic nerve hypoplasia and partially penetrant seizures in girls. The Cask+/- heterozygous knockout female mouse phenocopies the human disorder and exhibits postnatal microencephaly, cerebellar hypoplasia and optic nerve hypoplasia. It is not known if Cask+/- mice also display seizures, nor is known the molecular mechanism by which CASK haploinsufficiency produces the numerous documented phenotypes. 24-h video electroencephalography demonstrates that despite sporadic seizure activity, the overall electrographic patterns remain unaltered in Cask+/- mice. Additionally, seizure threshold to the commonly used kindling agent, pentylenetetrazol, remains unaltered in Cask+/- mice, indicating that even in mice the seizure phenotype is only partially penetrant and may have an indirect mechanism. RNA sequencing experiments on Cask+/- mouse brain uncovers a very limited number of changes, with most differences arising in the transcripts of extracellular matrix proteins and the transcripts of a group of nuclear proteins. In contrast to limited changes at the transcript level, quantitative whole-brain proteomics using iTRAQ quantitative mass-spectrometry reveals major changes in synaptic, metabolic/mitochondrial, cytoskeletal, and protein metabolic pathways. Unbiased protein-protein interaction mapping using affinity chromatography demonstrates that CASK may form complexes with proteins belonging to the same functional groups in which altered protein levels are observed. We discuss the mechanism of the observed changes in the context of known molecular function/s of CASK. Overall, our data indicate that the phenotypic spectrum of female Cask+/- mice includes sporadic seizures and thus closely parallels that of CASK haploinsufficient girls; the Cask+/- mouse is thus a face-validated model for CASK-related pathologies. We therefore surmise that CASK haploinsufficiency is likely to affect brain structure and function due to dysregulation of several cellular pathways including synaptic signaling and cellular metabolism.

19.
Zhonghua Jie He He Hu Xi Za Zhi ; 43(4): 356-361, 2020 Apr 12.
Artículo en Chino | MEDLINE | ID: mdl-32294818

RESUMEN

Objective: To explore the prevalence risk factors of Beijing genotype Mycobacterium tuberculosis (MTB) in Beijing and its correlation with second-line anti tuberculosis drug resistance. Methods: A total of 1 140 clinical MTB positive strains were collected from various districts in Beijing, and the drug sensitivity was detected by proportion method. Beijing genotype and non Beijing genotype MTB were identified by the method of Spoligotyping. Using SPSS 22.0 statistical software, chi square test or Fisher exact probability test was used to analyze the experimental data. Results: Among 1 140 MTB clinical isolates, 941 (82.5%) were Beijing genotype MTB, 199 were non Beijing genotype MTB. There were 663 males (70.5%) in Beijing genotype and 124 males (62.3%) in non Beijing genotype strains. There were significant differences in the proportion of males between the two genotypes [P=0.021, OR (95% CI):1.442 (1.048-1.985)]. There were 441 floating population (46.9%) in Beijing genotype MTB and 78 floating population (39.2%) in non Beijing genotype MTB. There was a significant difference in the proportion of floating population between the two genotypes [P=0.048,OR (95%CI):1.368(1.001-1.869)]. There were 129 patients (13.7%) aged 65 or older in Beijing genotype MTB, 40 patients (20.1%) aged 65 or older in non Beijing genotype MTB. The difference was statistically significant [P=0.021, or (95% CI): 0.631 (0.426-0.936)]. The resistance drug rates of Levofloxacin (Lfx), Amikacin (Am), Capreomycin (Cm), Para-aminosalicylic (PAS) in Beijing genotypes were 5.5% (52/941), 1.3% (12/941), 3.2% (30/941) and 3.0% (28/941), respectively, and those of non Beijing genotypes were 10.6% (21/199), 8.5% (17/199, 12.6% (25/199) and 11.6% (23/199), the difference was statistically significant (all P<0.05). There were 58 (6.2%) multidrug-resistant (MDR) strains in Beijing genotype MTB and 19 (9.5%) multidrug-resistant strains in non Beijing genotype. There was no significant difference in the proportion of MDR strains between Beijing genotype and non Beijing genotype (P>0.05). Conclusions: Beijing genotype MTB is widespread in Beijing and has a higher proportion in male population and floating population. Compared with non Beijing genotype, Beijing genotype MTB has a lower resistance rate to Lfx, Am, Cm and PAS, and there is no significant difference in the proportion of MDR-TB patients between the two genotypes.


Asunto(s)
Antituberculosos/uso terapéutico , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/genética , Tuberculosis Pulmonar/tratamiento farmacológico , Anciano , Antituberculosos/farmacología , China/epidemiología , ADN Bacteriano/genética , Farmacorresistencia Bacteriana Múltiple/genética , Genotipo , Humanos , Masculino , Mycobacterium tuberculosis/aislamiento & purificación , Prevalencia , Tuberculosis Pulmonar/epidemiología
20.
Zhonghua Wai Ke Za Zhi ; 58(6): 404-407, 2020 Jun 01.
Artículo en Chino | MEDLINE | ID: mdl-32253891

RESUMEN

As a newly epidemic, 2019 coronavirus disease (COVID-19) with a concentrated outbreak poses a great challenge to medical treatment. The severe and critical patients are complex complicatied with the psychological problems, and the medical staff are overworked and under tremendous psychological pressure. The surgeon participated in emergency medical rescue could provide professional treatment for the patients combined with surgical diseases, as well as specialized training for the non-surgeon crew, to reduce surgical-related mortality. With the advantages of good team consciousness, strong aseptic concept and good psychological quality, the surgeons can quickly adapt to and carry out rescue work under the premise of good self-protection. Surgeons need to develop critical care management concepts and focus on the critical care support equipment. Some suggestions are put forward for the standardized training of resident surgeons to cultivate compound talents. It is hoped that this article can lead to the thinking of how to participate in the emergency medical rescue of infectious diseases among surgeons and provide some enlightenment for future surgical education.


Asunto(s)
Infecciones por Coronavirus/terapia , Cuidados Críticos/normas , Prestación de Atención de Salud/normas , Manejo de Atención al Paciente/normas , Neumonía Viral/terapia , Práctica Profesional/normas , Cirujanos/normas , Betacoronavirus , Competencia Clínica , Cuidados Críticos/psicología , Urgencias Médicas , Humanos , Internado y Residencia/normas , Estrés Laboral/prevención & control , Pandemias , Cirujanos/educación , Cirujanos/psicología
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