Assessment of performance and comparison of three commercial HDV RNA detection assays: implications for diagnosis and treatment monitoring.

Objectives: Precise HDV-RNA detection and quantification are pivotal for diagnosis and monitoring of response to newly approved treatment. We evaluate the performance of three HDV RNA detection and quantification assays. Methods: Hepatitis Delta RT-PCR system kit, EurobioPlex HDV assay, and RoboGene HDV RNA Quantification kit 2.0 were used for testing 151 HBsAg-positive samples, 90 HDV-RNA negative and 61 HDV-RNA positive. We also evaluated serial dilutions of the WHO international standard for HDV, PEI 7657/12. All HDV-RNA positive samples were genotyped using a next-generation sequencing strategy. Results: Qualitative results indicated a 100% concordance between tests. Quantitative results correlated well, r2 = 0.703 (Vircell-vs-Eurobio), r2 = 0.833 (Vircell-vs-RoboGene), r2 = 0.835 (Robogene-vs-Eurobio). Bias index was 2.083 (Vircell-vs-Eurobio), -1.283 (Vircell-vs-RoboGene), and -3.36 (Robogene-vs-Eurobio). Using the WHO IS, Vircell overestimated the viral load by 0.98 log IU/mL, Eurobio by 1.46 log IU/mL, and RoboGene underestimated it by 0.98 log IU/mL. Fifty-nine samples were successfully genotyped (Genotype 1, n=52; Genotype 5, n=7; Genotype 6, n=1), with similar results for correlation and bias. Conclusion: This study underscores the necessity of using reliable HDV-RNA detection and quantification assays, as evidenced by the high concordance rates in qualitative detection and the observed variability in quantitative results. These findings highlight the importance of consistent assay use in clinical practice to ensure accurate diagnosis and effective treatment monitoring of HDV infection.

The Bern Birth Cohort (BeBiCo) to study the development of the infant intestinal microbiota in a high-resource setting in Switzerland: rationale, design, and methods.

BACKGROUND: Microbiota composition is fundamental to human health with the intestinal microbiota undergoing critical changes within the first two years of life. The developing intestinal microbiota is shaped by maternal seeding, breast milk and its complex constituents, other nutrients, and the environment. Understanding microbiota-dependent pathologies requires a profound understanding of the early development of the healthy infant microbiota. METHODS: Two hundred and fifty healthy pregnant women (≥20 weeks of gestation) from the greater Bern area will be enrolled at Bern University hospital's maternity department. Participants will be followed as mother-baby pairs at delivery, week(s) 1, 2, 6, 10, 14, 24, 36, 48, 96, and at years 5 and 10 after birth. Clinical parameters describing infant growth and development, morbidity, and allergic conditions as well as socio-economic, nutritional, and epidemiological data will be documented. Neuro-developmental outcomes and behavior will be assessed by child behavior checklists at and beyond 2 years of age. Maternal stool, milk, skin and vaginal swabs, infant stool, and skin swabs will be collected at enrolment and at follow-up visits. For the primary outcome, the trajectory of the infant intestinal microbiota will be characterized by 16S and metagenomic sequencing regarding composition, metabolic potential, and stability during the first 2 years of life. Secondary outcomes will assess the cellular and chemical composition of maternal milk, the impact of nutrition and environment on microbiota development, the maternal microbiome transfer at vaginal or caesarean birth and thereafter on the infant, and correlate parameters of microbiota and maternal milk on infant growth, development, health, and mental well-being. DISCUSSION: The Bern birth cohort study will provide a detailed description and normal ranges of the trajectory of microbiota maturation in a high-resource setting. These data will be compared to data from low-resource settings such as from the Zimbabwe-College of Health-Sciences-Birth-Cohort study. Prospective bio-sampling and data collection will allow studying the association of the microbiota with common childhood conditions concerning allergies, obesity, neuro-developmental outcomes , and behaviour. Trial registration The trial has been registered at www. CLINICALTRIALS: gov , Identifier: NCT04447742.

Real-life validation of a sample pooling strategy for screening of hepatitis C.

OBJECTIVES: To test a real-life sample pooling screening strategy which contributes to increasing the diagnostic capacity of clinical laboratories and expanding access to massive screening of hepatitis C. METHODS: After evaluating the sensitivity of the pooling strategy for seven different commercial assays which are used to determine the concentration of hepatitis C virus (HCV)-RNA in the plasma or serum, consecutive samples submitted for HCV diagnosis during the first 3 weeks of November 2021 were tested for HCV antibodies and, in parallel and in a blinded way, were pooled into 100 samples and tested for HCV-RNA. When the result was positive, a strategy to un-mask the positive(s) pool(s), which needed up to 15 total HCV-RNA tests, was used. RESULTS: All platforms were able to detect the presence of HCV-RNA in a single sample from a patient with viremic HCV present in pools of up to at least 10 000 HCV-RNA-free samples. A total of 1700 samples (17 pools) were analysed, with an overall prevalence of anti-HCV and HCV-RNA of 0.24%. After pooling, we could detect all samples previously detected using standard diagnosis tests (reflex testing) with a specificity and sensitivity of 100% (CI, 99.78-100%). Given the median current prices of anti-HCV and HCV-RNA on the market in Spain as well as personnel costs, testing using the pooling strategy would have resulted in a save of 3320€. CONCLUSIONS: Here, we demonstrated that by improving cost effectiveness, with no loss of sensitivity and specificity, the strategy of pooling samples may serve as an appropriate tool for use in large-scale screening of HCV.

The unexpected high prevalence of HBV subgenotype D4 in patients with chronic hepatitis B in Galicia, a northwestern Spanish region, reflects strong links with Latin America.

BACKGROUND: Hepatitis B virus (HBV) comprises 9 genotypes and multiple subgenotypes that depict differences in geographic distribution, clinical outcome and response to antiviral therapy. However, the molecular epidemiology of HBV geno/subgenotypes is globally scarce. In Spain, HBV genotype D seems to be more prevalent in the northwestern regions compared to the rest of the country for unclear reasons. METHODS: HBV genotyping was performed using geno2pheno on a S gene fragment amplified from plasma collected from all chronic hepatitis B individuals attended at one reference hospital in Santiago de Compostela, the Galicia's capital town. Phylogenetic and phylogeographic analyses using a fragment of 345 bp were performed in all viremic specimens. To avoid misleading allocation as consequence of short fragment analysis, several bioinformatic controls were used. RESULTS: A total of 320 individuals with persistent serum HBsAg+ and detectable HBV-DNA were seen between 2000 and 2016 (male 68.4%; median age, 52 years-old; native Spaniards 83.8%). HBV genotype distribution was as follows: A 15.3%; B 1.6%; C 2.5%; D 71.6%; E 3.1%; F 2.2%; G 3.1%; and H 0.6%. HBV genotype D was mostly represented by D4 and D2 subgenotypes (33.4% and 15% of total, respectively). Compared to chronic hepatitis B patients with genotypes B, C, E and G, HBV-D4 carriers tended to be older (54.2% had >50 years-old) and HBeAg-negative (85%). Moreover, 43% were female, 4.7% had cirrhosis, 10.2% hepatitis C and 6.4% HIV coinfection. Phylogenetic analyses could be performed on 82 HBV-D4 specimens; and 79 were confirmed as HBV-D4 using PhyML. Phylogeography using FasTree suggested at least two distinct introductions of HBV-D4 in Galicia, one from the Caribbean and South America, and another from India. CONCLUSIONS: HBV subgenotype D4 is the most prevalent HBV variant in chronic hepatitis B patients living in the northwest of Spain, representing 33.4% (107/320) of all chronic hepatitis B infections. This rate of HBV-D4 is among the highest reported worldwide. Epidemiological and phylogenetic analyses suggest a strong association with historical migrant exchanges with Latin America, and especially with the Caribbean basin.

SARS-CoV-2 in Conjunctiva and Tears and Ocular Symptoms of Patients with COVID-19.

This study investigates the presence of SARS-CoV-2 in conjunctival secretions and tears and evaluates ocular symptoms in a group of patients with COVID-19. We included 56 hospitalized patients with COVID-19 in this cross-sectional cohort study. Conjunctival secretions and tears were collected using flocked swabs and Schirmer strips for SARS-CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR). Assessment of ocular surface manifestations included an OSDI (Ocular Surface Disease Index) questionnaire. Patients had been admitted to hospital for an average of 2.4 days (range 0-7) and had shown general symptoms for an average of 7.1 days (range 1-20) prior to ocular testing. Four (7.1%) of 56 conjunctival swabs and four (4%) of 112 Schirmer strips were positive for SARS-CoV-2. The mean E-gene cycle threshold values (Ct values) were 31.2 (SD 5.0) in conjunctival swabs and 32.9 (SD 2.7) in left eye Schirmer strips. Overall, 17 (30%) patients presented ocular symptoms. No association was found between positive ocular samples and ocular symptoms. This study shows that SARS-CoV-2 can be detected on the conjunctiva and tears of patients with COVID-19. Contact with the ocular surface may transmit the virus and preventive measures should be taken in this direction.

Estrategias de enseñanza y aprendizaje de docentes y estudiantes de primer año de la carrera de kinesiología de la Universidad Finis Terrae / Learning strategies for first-year teachers and students of the physical therapy program at Universersity Finis Terrae

Las estrategias de aprendizaje explican el curso y organización del pensamiento, destacando tres momentos claves en su utilización: antes, donde se incluyen las condiciones para que ocurra el aprendizaje; durante, donde se llevan a cabo los procesos; y después, que presentan los resultados de esta secuencia. Para determinar cuáles son las estrategias que utilizan los estudiantes de primer año de Kinesiología se aplicó a 75 estudiantes el instrumento ACRA abreviado, que consiste en un cuestionario autoadministrado de 44 preguntas de escala Likert, Por otro lado, para conocer las estrategias que los docentes necesitan y exigen a sus estudiantes se realizó una encuesta estructurada validada por juicio de expertos a 5 profesores encargados de asignatura. Los resultados en los estudiantes destacan que la codificación es el proceso que presenta mayor debilidad y en los docentes destaca que, si bien se les exigen determinadas estrategias a los estudiantes, los docentes declaran no saber cómo enseñarlas. Esto contribuye a la persistencia de la brecha que los estudiantes traen desde la educación media en las estrategias de codificación y evidencia la necesidad de capacitación de los docentes.

The learning strategies explain the course and organization of thought, highlighting three key moments on their use: before, where the conditions for learning occurs are included; during, where the processes are carried out; and later, presenting the results of this sequence. To determine which are the strategies used for first-year Kinesiology students, the abbreviated ACRA instrument was applied to 75 students, which consists of a self-administrated questionnaire of 44 Likert Scale questions, and to know the strategies that teachers need that students have, a structured survey validated by expert's judgment was carried out to 5 teachers in charge of a course. The results in the students highlight that coding is the process that presents the greatest weakness and, in the teachers, although students are required to have certain strategies, the teachers declare that they do not know how to teach those. This contributes to the persistence of the gap that students bring from high school in coding strategies and shows the need for training in pedagogical tools for university teachers.

Locally adaptive decision in detection of clustered microcalcifications in mammograms.

In computer-aided detection or diagnosis of clustered microcalcifications (MCs) in mammograms, the performance often suffers from not only the presence of false positives (FPs) among the detected individual MCs but also large variability in detection accuracy among different cases. To address this issue, we investigate a locally adaptive decision scheme in MC detection by exploiting the noise characteristics in a lesion area. Instead of developing a new MC detector, we propose a decision scheme on how to best decide whether a detected object is an MC or not in the detector output. We formulate the individual MCs as statistical outliers compared to the many noisy detections in a lesion area so as to account for the local image characteristics. To identify the MCs, we first consider a parametric method for outlier detection, the Mahalanobis distance detector, which is based on a multi-dimensional Gaussian distribution on the noisy detections. We also consider a non-parametric method which is based on a stochastic neighbor graph model of the detected objects. We demonstrated the proposed decision approach with two existing MC detectors on a set of 188 full-field digital mammograms (95 cases). The results, evaluated using free response operating characteristic (FROC) analysis, showed a significant improvement in detection accuracy by the proposed outlier decision approach over traditional thresholding (the partial area under the FROC curve increased from 3.95 to 4.25, p-value <10-4). There was also a reduction in case-to-case variability in detected FPs at a given sensitivity level. The proposed adaptive decision approach could not only reduce the number of FPs in detected MCs but also improve case-to-case consistency in detection.

Estimating the Accuracy Level Among Individual Detections in Clustered Microcalcifications.

Computerized detection of clustered microcalcifications (MCs) in mammograms often suffers from the occurrence of false positives (FPs), which can vary greatly from case to case. We investigate how to apply statistical estimation to determine the number of FPs that are present in a detected MC lesion. First, we describe the number of true positives (TPs) by a Poisson-binomial probability distribution, wherein a logistic regression model is trained to determine the probability for an individual detected MC to be a TP based on its detector output. Afterward, we model the spatial occurrence of FPs in a lesion area by a spatial point process (SPP), of which the distribution parameters are estimated from the detections in the lesion and its surrounding region. Furthermore, to improve the estimation accuracy, we incorporate the Poisson-binomial distribution of the number of TPs into the SPP model using maximum a posteriori estimation. In the experiments, we demonstrated the proposed approach on the detection results from a set of 188 full-field digital mammography (FFDM) images (95 cases) by three existing MC detectors. The results showed that there was a strong consistency between the estimated and the actual number of TPs (or FPs) for these detectors. When the fraction of FPs in detection was varied from 20% to 50%, both the mean and median values of the estimation error were within 11% of the total number of detected MCs in a lesion. In particular, when the number of FPs increased to as high as 11.38 in a cluster on average, the error was 2.51 in the estimated number of FPs. In addition, lesions estimated to be more accurate in detection were shown to have better classification accuracy (for being malignant or benign) than those estimated to be less accurate.

Las teorías subjetivas del profesor acerca de su salud laboral: Implicancias en la promoción de la salud preventiva en el trabajo docente / Subjective theories of teacher about their occupational health: Implications in promoting preventive health in teaching job

Se reportan los resultados de una investigación cualitativa que tuvo como objetivo describir e interpretar las teorías subjetivas de docentes acerca de su salud laboral. Se trabajó con 46 profesores de cuatro liceos públicos de dos comunas de la Región de Atacama, Chile, que se seleccionaron bajo el criterio de representatividad de casos. Se aplicaron ocho entrevistas en profundidad y seis grupos de discusión. Mediante la técnica de análisis de la Grounded Theory y análisis específico para teorías subjetivas; se encontró que las teorías subjetivas sobre salud laboral docente están relacionadas con los significados subjetivos que los docentes le otorgan a la profesión, enseñanza y aprendizaje de sus estudiantes, y que las características de su estructura y contenido conllevan más bien a una inhibición del autocuidado de su salud laboral. En la discusión se analiza la implicancia que esto tiene para la salud laboral del profesor y se proponen orientaciones que podrían propiciar, a partir del cambio subjetivo, el desarrollo de teorías subjetivas de mayor elaboración y complejidad, que orienten la acción hacia el autocuidado de la salud laboral docente.

The results of a qualitative study aimed to describe and interpret the subjective theories of teachers about their occupational health is reported. We worked with 46 teachers from four public secondary education in the towns of the Atacama Region, Chile, which were selected under the criteria of representativeness of cases. Eight interviews and six focus groups were applied. Through technical analysis of Grounded Theory and subjective theories specific analysis revealed that subjective theories on occupational health teaching are closely related to the subjective meanings that teachers give to the profession, teaching and student learning, and that the characteristics of the structure and content rather lead to an inhibition of self-care in occupational health. In discussing the implications of this for occupational health teacher and guidance that could lead, from subjective change, the development of subjective theories of elaboration and greater complexity, to guide action towards self-care proposed occupational health teacher analyzed.

Tumor osteoclástico del páncreas / Osteoclastic tumour of the pancreas

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