Neglected intrapulmonary arteriovenous anastomoses: A comparative study of pulmonary right-to-left shunts in patients with patent foramen ovale

ObjectivePulmonary right-to-left shunt (P-RLS) and patent foramen ovale right-to-left shunt (PFO-RLS) often appear in combination, and there are often differences and connections between them. Intrapulmonary arteriovenous anastomoses (IPAVAs), as part of P-RLS, are often overlooked because there are no technologies to detect and identify them. This study aimed to further clarify the incidence and characteristics of P-RLS with the help of contrast transesophageal echocardiography (c-TEE) and contrast transthoracic echocardiography (c-TTE), providing a reference for clinically relevant research and patent foramen ovale (PFO) management disposal decisions.MethodsWe retrospectively investigated 414 subjects who came to our hospital for c-TEE from October 2021 to July 2022, and all subjects completed c-TTE simultaneously. 7 Patients who were newly diagnosed with an atrial septal defect were excluded. Eventually, 407 patients were included in this study. Among them, 157 patients with PFO (58 patients were treated with PFO closure subsequently) and 250 patients without PFO confirmed by c-TEE were finally enrolled. In the process, we observed and analysed the presence of P-RLS.ResultsA total of 407 patients were included in the final analysis and divided into PFO group (N = 157) and non-PFO group (N = 250) according to the results of c-TEE. Whether at rest or after Valsalva maneuver, the incidence of P-RLS was significantly higher under c-TEE than under c-TTE in the two groups (P < 0.001). For both c-TTE and c-TEE, the incidence of P-RLS was slightly higher after Valsalva maneuver than at rest, but the difference was not significant (c-TTE: rest vs. Valsalva maneuver, P = 0.214; c-TEE: rest vs. Valsalva maneuver, P = 0.076). The Valsalva maneuver increased the incidence of P-RLS in the group without PFO, which was more significant in c-TEE (c-TTE: rest vs. Valsalva maneuver, P = 0.591; c-TEE: rest vs. Valsalva maneuver, P = 0.008). In both groups, the P-RLS semiquantitative grading was statistical significance under different states and examinations (P < 0.001).ConclusionThe vast majority of P-RLS are grade 1–2 and are derived from physiological IPAVAs. Even so, attention should be given to the differentiation between P-RLS and PFO-RLS. c-TEE is an effective method to detect P-RLS; however, the recruitments of c-TEE and Valsalva maneuver to P-RLS should be noted

Calf muscle pump tensing as a novel maneuver to improve the diagnostic performance of detecting patent foramen ovale during transesophageal echocardiography

ObjectiveThe Valsalva maneuver is the most sensitive provocative maneuver for patent foramen ovale detection. However, nearly half of patients are unable to perform the Valsalva maneuver well. The aim of this study was to investigate the mechanism of action of calf muscle pump tensing (TENSE) as a novel patent foramen ovale (PFO) provocative maneuver and to evaluate the diagnostic value for PFO and the effect on right-to-left shunt volume compared with the Valsalva maneuver.MethodsThis study prospectively investigated 171 patients who were highly suspected to have PFO clinically. Five patients with atrial septal defects newly diagnosed on transesophageal echocardiography (TEE) were excluded. 166 patients were injected with agitated saline under three provocative maneuvers: Valsalva maneuver, TENSE, and Valsalva + TENSE combined maneuver. The patients were divided into the effective Valsalva group (n = 93) and ineffective Valsalva group (n = 73) according to whether they could perform an effective Valsalva maneuver. TENSE consisted of the straightening of both lower limbs, and when the right atrium was filled with microbubbles, the patient performed instantaneous ankle dorsiflexion movements while maintaining dorsiflexion for 3–5 s.ResultsOverall, the PFO detection rate of the Valsalva + TENSE combined maneuver (78 [50.1%]) was significantly higher than that of the Valsalva maneuver (51 [30.7%]) and TENSE maneuver (57 [34.3%]) (P < 0.001). In the patients who were able to perform an effective Valsalva maneuver, the PFO detection rate by TENSE was not significantly different from that by the Valsalva maneuver (Valsalva 37/93 [39.8%] vs. TENSE 31/93 [33.3%], P > 0.05), while for the patients who performed an ineffective Valsalva maneuver, the PFO detection rate by the TENSE maneuver was higher than that by the Valsalva maneuver (TENSE 26/73 [35.6%] vs. Valsalva14/73[19.2%], P = 0.017).ConclusionTENSE is a simple and effective provocative maneuver in the diagnosis of PFO using TEE and can assist the Valsalva maneuver. For patients who cannot perform an effective Valsalva maneuver, TENSE can be an alternative to the Valsalva maneuver to some extent

Maternal supplementation with Limosilactobacillus reuteri FN041 for preventing infants with atopic dermatitis: study protocol for a randomized controlled trial

BackgroundAtopic dermatitis (AD) has increased rapidly with rapid urbanization; however, the treatment options for AD are lacking because the commonly used therapies can only alleviate symptoms. Limosilactobacillus reuteri (L. reuteri), FN041 is a specific strain isolated from human breast milk, and its protective potential against AD has been confirmed. This study aims to assess the efficacy of maternal consumption of L. reuteri FN041 during late pregnancy and lactation in preventing infantile AD.MethodsFirst, a randomized, double-blind, placebo-controlled intervention study will be conducted on 340 pregnant females with babies at high risk for AD. These subjects will be randomly divided into four groups of different doses of L. reuteri FN041 (1 × 109, 5 × 109, and 1 × 1010 CFU/d) along with a placebo. The safety and efficacy of maternal use of L. reuteri FN041 for preventing infantile AD will be analyzed, and the most efficient dosage of L. reuteri FN041 will be determined. Subsequently, a multicenter cohort study of 500 pregnant females with babies at high risk for AD will be conducted to promote the maternal application of L. reuteri FN041. These subjects will be administered L. reuteri FN041 at the optimal dose determined during the first stage of late pregnancy and lactation, and their babies will be analyzed for AD development. Recruitment was initiated in October 2022.DiscussionThe primary outcome is the cumulative incidence of AD at 24 months after maternal consumption of L. reuteri FN041 during late pregnancy and lactation, whereas the secondary outcome is the efficiency of L. reuteri FN041 transfer from the mother’s gut to breast milk and then the infant’s gut after oral supplementation. This study will demonstrate the efficacy of edible probiotics isolated from breast milk in preventing or treating AD in infants. Accordingly, we provide population-based advice for administering specific probiotics for the primary prevention of AD in pregnant females. Understanding the underlying mechanisms of probiotic strains derived from breast milk can promote their application in preventing infant diseases associated with intestinal microbiota imbalance and immune disorders.Clinical trial registrationhttps://www.chictr.org.cn/, identifier [ChiCTR2300075611]

Mapping current trends and hotspots in myasthenia gravis from 2003 to 2022: a bibliometric analysis

IntroductionResearch on myasthenia gravis (MG) has undergone rapid development in recent years. This article aimed to elucidate the characteristics of MG publications over the past 20 years and analyze emerging trends using bibliometric methods.MethodsInformation on MG articles was obtained from the Web of Science Core Collection and stored in Excel for quantitative analyses. Bibliometric analyses were performed using CiteSpace and VOSviewer to visualize publications according to countries/regions, institutions, journals, and authors.ResultsA total of 3,610 publications were included in the analysis. The USA had the highest number of publications (NP) and H-index. Among the institutions, the University of Oxford had the highest NP, followed by the University of Toronto and Duke University. Close cooperation was observed among countries and institutions. The most productive author was Renato Mantegazza, followed by Jan J. Verschuuren, and Amelia Evoli. Muscle & Nerve published the most articles on MG, followed by the Journal of Neuroimmunology and Neuromuscular Disorders. The keyword with the highest strength is “neuromuscular transmission,” followed by “safety” and “rituximab.” Co-citation analysis includes 103 publications cited at least 65 times, categorized into four clusters. Additionally, 123 keywords cited more than 40 times were analyzed and divided into five clusters.ConclusionThis bibliometric analysis shows the framework of research over the past 20 years by mapping the scholarly contributions of various countries or regions, institutions, journals, and authors in MG. The analysis also explores future trends and prospective directions, emphasizing individualized treatment based on subtypes, novel immunotherapeutic approaches, and thymectomy

Minimal residual disease monitoring in childhood Philadelphia chromosome-positive acute lymphoblastic leukemia: prognostic significance and correlation between multiparameter flow cytometry and real-time quantitative polymerase chain reaction

Not available

HECT, UBA and WWE domain containing 1 represses cholesterol efflux during CD4+ T cell activation in Sjögren’s syndrome

Introduction: Sjögren’s syndrome (SS) is a chronic autoimmune disorder characterized by exocrine gland dysfunction, leading to loss of salivary function. Histological analysis of salivary glands from SS patients reveals a high infiltration of immune cells, particularly activated CD4+ T cells. Thus, interventions targeting abnormal activation of CD4+ T cells may provide promising therapeutic strategies for SS. Here, we demonstrate that Hect, uba, and wwe domain containing 1 (HUWE1), a member of the eukaryotic Hect E3 ubiquitin ligase family, plays a critical role in CD4+ T-cell activation and SS pathophysiology.Methods: In the context of HUWE1 inhibition, we investigated the impact of the HUWE1 inhibitor BI8626 and sh-Huwe1 on CD4+ T cells in mice, focusing on the assessment of activation levels, proliferation capacity, and cholesterol abundance. Furthermore, we examined the therapeutic potential of BI8626 in NOD/ShiLtj mice and evaluated its efficacy as a treatment strategy.Results: Inhibition of HUWE1 reduces ABCA1 ubiquitination and promotes cholesterol efflux, decreasing intracellular cholesterol and reducing the expression of phosphorylated ZAP-70, CD25, and other activation markers, culminating in the suppressed proliferation of CD4+ T cells. Moreover, pharmacological inhibition of HUWE1 significantly reduces CD4+ T-cell infiltration in the submandibular glands and improves salivary flow rate in NOD/ShiLtj mice.Conclusion: These findings suggest that HUWE1 may regulate CD4+ T-cell activation and SS development by modulating ABCA1-mediated cholesterol efflux and presents a promising target for SS treatment

International Asteroid Warning Network Timing Campaign : 2019 XS

Peer reviewe

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity

Формирование эмоциональной культуры как компонента инновационной культуры студентов

Homozygosity has long been associated with rare, often devastating, Mendelian disorders1 and Darwin was one of the first to recognise that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity, ROH), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3,4. Here we use ROH to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts and find statistically significant associations between summed runs of homozygosity (SROH) and four complex traits: height, forced expiratory lung volume in 1 second (FEV1), general cognitive ability (g) and educational attainment (nominal p<1 × 10−300, 2.1 × 10−6, 2.5 × 10−10, 1.8 × 10−10). In each case increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing convincing evidence for the first time that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5,6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein (LDL) cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been