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To compare single-molecule real-time technology (SMRT) and conventional genetic diagnostic technology of rare types of thalassemia mutations, and to analyze the molecular characteristics and phenotypes of rare thalassemia gene variants, we used 434 cases with positive hematology screening as the cohort, then used SMRT technology and conventional gene diagnosis technology [(Gap-PCR, multiple ligation probe amplification technology (MLPA), PCR-reverse dot blot (RDB)] for thalassemia gene screening. Among the 434 enrolled cases, conventional technology identified 318 patients with variants (73.27%) and 116 patients without variants (26.73%), SMRT identified 361 patients with variants (83.18%), and 73 patients without variants (16.82%). The positive detection rate of SMRT was 9.91% higher than conventional technology. Combination of the two methods identified 485 positive alleles among 49 types of variant. The genotypes of 354 cases were concordant between the two methods, while 80 cases were discordant. Among the 80 cases, 76 cases had variants only identified in SMRT method, 3 cases had variants only identified in conventional method, and 1 false positive result by the traditional PCR detection technology. Except the three variants in HS40 and HBG1-HBG2 loci, which was beyond the design of SMRT method in this study, all the other discordant variants identified by SMRT were validated by further Sanger sequencing or MLPA. The hematological phenotypic parameters of 80 discordant cases were also analyzed. SMRT technology increased the positive detection rate of thalassemia genes, and detected rare thalassemia cases with variable phenotypes, which had great significance for clinical thalassemia gene screening.Disruptions in frontoparietal networks supporting emotion regulation have been long implicated in maladaptive childhood aggression. However, the association of connectivity between large-scale functional networks with aggressive behavior has not been tested. The present study examined whether the functional organization of the connectome predicts severity of aggression in children. This cross-sectional study included a transdiagnostic sample of 100 children with aggressive behavior (27 females) and 29 healthy controls without aggression or psychiatric disorders (13 females). Severity of aggression was indexed by the total score on the parent-rated Reactive-Proactive Aggression Questionnaire. During fMRI, participants completed a face emotion perception task of fearful and calm faces. Connectome-based predictive modeling with internal cross-validation was conducted to identify brain networks that predicted aggression severity. The replication and generalizability of the aggression predictive model was then tested in an independent sample of children from the Adolescent Brain Cognitive Development (ABCD) study. Connectivity predictive of aggression was identified within and between networks implicated in cognitive control (medial-frontal, frontoparietal), social functioning (default mode, salience), and emotion processing (subcortical, sensorimotor) (r = 0.31, RMSE = 9.05, p = 0.005). Out-of-sample replication (p less then 0.002) and generalization (p = 0.007) of findings predicting aggression from the functional connectome was demonstrated in an independent sample of children from the ABCD study (n = 1791; n = 1701). Individual differences in large-scale functional networks contribute to variability in maladaptive aggression in children with psychiatric disorders. Linking these individual differences in the connectome to variation in behavioral phenotypes will advance identification of neural biomarkers of maladaptive childhood aggression to inform targeted treatments.
Workers and residents of care facilities for elder people/people with disabilities were particularly hit by the COVID-19 pandemic. Workers from these centres were included as a priority group for vaccination against SARS-CoV-2. The Family Ministry of Castilla y León realized a seroprevalence survey measuring the humoral immunity of its workers after the vaccination against SARS-CoV-2.
In February and March 2021, IgM/IgG antibodies were measured in 7 social health care centers in a total of 1,085 workers at least 15 days after completing the vaccination with the BNT162b2 vaccine from Pfizer/BioNtech. Using the ELISA technique for anti-nucleocapsid (N) IgM and CLIA S-RBD SARS-CoV-2 for anti-spicule (S) IgG, titers were compared between vaccinated with cero, one or two doses, and differentiating in these subgroups between having passed or not COVID-19. Means and percentages were compared using Student's t and Chi2 (EPIDAT 3.1).
Among the 1,085 workers studied, there were 54 workers with a single dose of vamoral immunity against SARS-CoV-2 could be considered as a parameter for sufficient immunity.
99.8% of social health workers who received 2 doses of the BNT162b2 vaccine from Pfizer/BioNtech, and 94% of those who received 1 single dose, presented humoral immunity with high IgG titers, with high clinical effectiveness expressed in the absence of cases. 64% of unvaccinated workers presented humoral immunity. The history of having passed COVID-19 produces an important booster effect both after one and after two doses of vaccine. Measurement of humoral immunity against SARS-CoV-2 could be considered as a parameter for sufficient immunity.
The advance of the pandemic in the large cities of the world with great virulence and the apparent heterogeneous distribution by factors of vulnerability, led us to propose this work. The objective of this study was to relate COVID-19 infection rates to the social vulnerability of the city of Madrid by district, in two different episodes, spring 2020 and summer 2020.
Analytical cross-sectional study. Taking sociodemographic data of the entire population of the city of Madrid between the months of April and October 2020, together with the cumulative incidence rates of COVID-19, a linear regression analysis, correlation and factor analysis was carried out, relating the cumulative incidence rate of COVID-19 and the vulnerability indicator of the districts of the city of Madrid.
The results showed important differences between the two episodes of the pandemic on one hand, the first had more relationship with health factors, while in the second, a relationship appeared with the groups of greater social vulnerability, territorially located in the South-East of the City and related in this case to social factors rather than health. Thus we see that the TIA x 100,000 in the first episode in Chamberí and Usera -two extreme districts in vulnerability- were 896 and 843 cases respectively, while in the second they were 3,708 and 6,258 cases.
The territorial differences in the city become evident with the arrival of a generalised, universal event such as COVID-19, where vulnerability increases for everyone, with greater repercussions in those territories where it already had an impact.
The territorial differences in the city become evident with the arrival of a generalised, universal event such as COVID-19, where vulnerability increases for everyone, with greater repercussions in those territories where it already had an impact.Some of the most challenging guidelines for clinical practice include recommendations for disease prevention, which often involve lifestyle modifications, which may vary between populations. find more On August 30, 2021, the European Society of Cardiology (ESC) published new guidelines for primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD), endorsed by 12 European professional societies. Important features of the 2021 ESC guidelines include recommendations for disease prevention in individuals in clinical practice, including in older adults, with and without ASCVD, with diabetes, familial hypercholesterolemia, and chronic kidney disease (CKD). Importantly, and for the first time, the updated 2021 ESC guidelines also address the impact of environmental factors, including water, air, and soil pollution, on the risk of ASCVD. This Editorial aims to present and discuss how the latest 2021 ESC guidelines on the prevention of ASCVD have practical real-world applications in clinical practice.BACKGROUND RNA N6-methyladenosine (m6A) methylation, the most abundant and prominent form of epigenetic modification, is involved in hepatocellular carcinoma (HCC) initiation and progression. However, the role of m6A methylation in HCC tumor microenvironment (TME) formation is unexplored. This study aimed to reveal the TME features of HCC patients with distinct m⁶A expression patterns and establish a prognostic model based on m⁶A signatures for HCC cohorts. MATERIAL AND METHODS We classified the m⁶A methylation patterns in 365 HCC samples based on 21 m6A modulators using a consensus clustering algorithm. Single-sample gene set enrichment analysis algorithm was used to quantify the abundance of immune cell infiltration. Gene set variation analysis revealed the biological characteristics between the m⁶A modification patterns. The m6A-based prognostic model was constructed using a training set with least absolute shrinkage and selection operator regression and validated in internal and external datasets. RESULTS Two distinct m⁶A modification patterns exhibiting different TME immune-infiltrating characteristics, heterogeneity, and prognostic variations were identified in the HCC cohort. After depicting the immune landscape of TME in HCC, we found patients with high LRPPRC m⁶A modulator expression had depletion of T cells, cytotoxic cells, dendritic cells, and cytolytic activity response. A high m⁶A score, characterized by suppression of immunity, indicated an immune-excluded TME phenotype, with poor survival. A nomogram was developed to facilitate HCC clinical decision making. CONCLUSIONS Our results highlight the nonnegligible role of m6A methylation in TME formation and reveal a potential clinical application of the m⁶A-associated prognostic model for patients with HCC.BACKGROUND Biliary leak is a relatively uncommon but potentially severe complication of liver transplantation. Duct of Luschka (also known as subvesical bile ducts) is a term that refers to a number of accessory biliary ducts. While leaks from Ducts of Luschka are well-described in the field of hepatobiliary surgery, only 2 case reports of such leaks exist in the setting of liver transplant. CASE REPORT We report the first case of a Duct of Luschka biliary leak seen after DCD liver transplant in a 41-year-old woman with cirrhosis secondary to primary sclerosing cholangitis. The patient underwent surgical re-exploration in the immediate postoperative period due to bilious output from a surgical drain. A Duct of Luschka was found intraoperatively at the gallbladder fossa and was oversewn. Apart from immunosuppression-related neutropenia, the patient recovered uneventfully. CONCLUSIONS Given the variability in preoperative detection of subvesical bile ducts, accessory bile duct leak remains an important consideration in the liver transplant perioperative period. The prevalence of Ducts of Luschka and the relative risk of leakage from such subvesical bile ducts in liver transplants compared to cholecystectomies are unclear. Further research into anatomical accessory bile duct variants and preoperative techniques for detecting such ducts is warranted.
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