Background:The medical, health service, societal and economic impact of the COVID-19 emergency has unknown effects on overall population mortality. Previous models of population mortality are based on death over days among infected people, nearly all of whom (to date at least) have underlying conditions. Models have not incorporated information on high risk conditions or their longer term background (pre-COVID-19) mortality. We estimated the excess number of deaths over 1 year under different COVID-19 incidence rates and differing mortality impacts. Methods:Using population based linked primary and secondary care electronic health records in England (HDR UK -CALIBER), we report the prevalence of underlying conditions defined by UK Public Health England COVID-19 guidelines (16 March 2020) in 3,862,012 individuals aged ≥30 years from 1997-2017. We used previously validated phenotypes, openly available (https://caliberresearch.org/portal), for each condition using ICD-10 diagnosis, Read, procedure and medication codes. We estimated the 1-year mortality in each condition, and developed simple models of excess COVID-19-related deaths assuming relative risk (RR) of the impact of the emergency (compared to background mortality) of 1.2, 1.5 and 2.0.

The adaptor CARD9 functions downstream of C-type lectin receptors (CLRs) for the sensing of microbial infection, which leads to responses by the T1 and T17 subsets of helper T cells. The single-nucleotide polymorphism rs4077515 at CARD9 in the human genome, which results in the substitution S12N (CARD9), is associated with several autoimmune diseases. However, the function of CARD9 has remained unknown. Here we generated CARD9 knock-in mice and found that CARD9 facilitated the induction of type 2 immune responses after engagement of CLRs. Mechanistically, CARD9 mediated CLR-induced activation of the non-canonical transcription factor NF-κB subunit RelB, which initiated production of the cytokine IL-5 in alveolar macrophages for the recruitment of eosinophils to drive T2 cell-mediated allergic responses. We identified the homozygous CARD9 mutation encoding S12N in patients with allergic bronchopulmonary aspergillosis and revealed activation of RelB and production of IL-5 in peripheral blood mononuclear cells from these patients. Our study provides genetic and functional evidence demonstrating that CARD9 can turn alveolar macrophages into IL-5-producing cells and facilitates T2 cell-mediated pathologic responses.

BackgroundThe ongoing rise in the prevalence of hypertension in children and adolescents is considered to be accompanied with the epidemic of childhood overweight and obesity. In this study, we established a large scale cross-sectional study in Shanghai, China, which presented a new evidence for the correlation of hypertension prevalence with overweight and obesity stages in Chinese children and adolescents.MethodsA school-based cross-sectional study was conducted during February to December 2009 in Shanghai, China, including total 78,114 children and adolescents. Body weight, height, waist circumference (WC) and blood pressure (BP) were measured. Overweight and obesity were defined according to sex- and age- specific Chinese reference data.ResultsBoth SBP and DBP were very significantly increased in overweight (OW) and obese (OB) groups. With age and sex controlled, BMI and WC were independently positively correlated with SBP and DBP. The prevalence of high SBP, DBP and hypertension were markedly higher among OW and OB children than normal weight (NW) group. Odds ratios (ORs) for high SBP, high DBP and high BP were significantly greater in OW and OB children than NW group, and showed a trend increase correlating with obesity stages (all P <0.0001). According to the increasing OR with different combination of obese status of BMI and WC, WC has a stronger influence on hypertension. The combination of BMI and WC obese shows substantially higher ORs compared with those for either BMI or WC obese alone.ConclusionsIn this study on a large school-based population in Shanghai, China, BMI and WC are positively correlated with SBP and DBP. Being overweight or obese greatly increased the risk of hypertension in Chinese children and adolescents, in which WC is considered as a more sensitive indicator than BMI.

Coronavirus, or COVID-19, is a hazardous disease that has endangered the health of many people around the world by directly affecting the lungs. COVID-19 is a medium-sized, coated virus with a single-stranded RNA. This virus has one of the largest RNA genomes and is approximately 120 nm. The X-Ray and computed tomography (CT) imaging modalities are widely used to obtain a fast and accurate medical diagnosis. Identifying COVID-19 from these medical images is extremely challenging as it is time-consuming, demanding, and prone to human errors. Hence, artificial intelligence (AI) methodologies can be used to obtain consistent high performance. Among the AI methodologies, deep learning (DL) networks have gained much popularity compared to traditional machine learning (ML) methods. Unlike ML techniques, all stages of feature extraction, feature selection, and classification are accomplished automatically in DL models. In this paper, a complete survey of studies on the application of DL techniques for COVID-19 diagnostic and automated segmentation of lungs is discussed, concentrating on works that used X-Ray and CT images. Additionally, a review of papers on the forecasting of coronavirus prevalence in different parts of the world with DL techniques is presented. Lastly, the challenges faced in the automated detection of COVID-19 using DL techniques and directions for future research are discussed.

Study Design Histological features of the intervertebral disc (IVD)-endplate interface were analyzed. Objective To define cartilaginous and bony vertebral endplate in commonly used laboratory animals and compare with that of the humans. Summary of Background Data Endplates are crucial for the IVD nutrient supply: the IVDs have limited blood supply; most nutrients diffuse through endplates to nourish the discs. Various animal models of IVD and endplate degeneration have been used to study the etiology and treatments of spinal disorders. However, because humans are biped, the spine mechanics differ significantly from other mammals. Translation of animal research findings requires a characterization and comparison of the vertebral endplate in the respective species. In this study, we compared the endplate structure of laboratory animal species at the age range commonly used for modeling spine degeneration with that of an adult human. Methods Mouse, rat, rabbit, goat, and human IVDs and the adjacent vertebral bodies were isolated from the lower lumbar spine. Tissues were stained with Alcian Blue, counterstained with hematoxylin and eosin. Results Structure of the vertebral endplate varied significantly between the adult animal species and that of the humans. Growth plates persisted in all adult animals studied, whereas the growth plate is absent in the adult humans. In the mice and rats, the cartilaginous endplates are in continuation with the growth plates, with only a small bony center. Rabbits and goats have a bony layer between cartilaginous endplate and the growth plate. The human endplate consist of a cartilaginous layer and the bony endplate. Conclusion Significant differences exist in histological features of the endplate across animal species and that of the humans. Consideration should be given when animal models are used to study IVD degeneration and surgical treatments.

Neonatal sepsis (NS) remains a major cause of morbidity and mortality in neonates, but data on the etiology and antibiotic susceptibility patterns of pathogens are limited. The aim of this study was to analyze the clinical characteristics, risk factors, and the antibiotic susceptibility patterns of pathogenic microbes associated with NS at a tertiary children's hospital in Shanghai, China. Episodes of blood culture-proven sepsis in the neonatal intensive care unit (NICU) of Children's Hospital of Fudan University from January 2013 to August 2017 were retrospectively reviewed. Collected data included demographics, perinatal risk factors, clinical symptoms, laboratory values, microbiology results and their antimicrobial susceptibility. Data for early-onset neonatal sepsis (EONS) and late-onset neonatal sepsis (LONS) were compared. The 341 of 976 culture-positive cases were selected, including 161 EONS cases (47.21% of 341) and 180 LONS cases (52.79% of 341). 635 incomplete cases were excluded. There was significant difference in risk factors between the EONS group and LONS group including birth weight, gestational age, 1-minute Apgar score, respiratory support, and the use of peripherally insertion central catheter (PICC). Clinical symptoms such as fever, feeding intolerance, abdominal distension, and neonatal jaundice, and laboratory results such as hemoglobin and lymphocyte counts also showed between-group differences. Staphylococcus epidermidis (22.87%) , Escherichia coli (9.68%), Alcaligenes xylosoxidans (9.38%) and Klebsiella pneumoniae (9.09%) remain the principal organisms responsible for neonatal sepsis. Most isolates of Gram-positive bacteria were sensitive to vancomycin, linezolid, minocycline and tigecycline, of which more than 90% were resistant to penicillin. Most isolates of Gram-negative bacteria were sensitive to amikacin and imipenem and resistant to ampicillin. Fungus was sensitive to antifungal agents. Better medical decisions, especially early detection and appropriate initial antimicrobial therapy can be made after understanding the different clinical features and pathogens of EONS and LONS.

Objective To examine the link between cytokines in intervertebral disc (IVD) tissues and axial back pain. Design In vitro study with human IVD cells cultured from cadaveric donors and annulus fibrosus (AF) tissues from patients. Results Cultured nucleus pulposus (NP) and AF cells were stimulated with interleukin (IL)-1β. IL-8 and IL-7 gene expression was analyzed using real-time PCR. IL-8 protein was quantified by ELISA. Following IL-1β stimulation, IL-8 gene expression increased 26,541 fold in NP cells and 22,429 fold in AF cells, while protein released by the NP and AF cells increased 2,389 and 1,784 fold, respectively. IL-7 gene expression increased 3.3 fold in NP cells (p<0.05). Cytokine profiles in AF tissues collected from patients undergoing surgery for back pain (painful group) or scoliosis (controls) were compared by cytokine array. IL-8 protein in the AF tissues from patients with back pain was 1.81 fold of that in controls. IL-7 and IL-10 in AF tissues from the painful group were, respectively, 6.87 and 4.63 times greater than the corresponding values in controls (p<0.05). Conclusion Inflammatory mediators found in AF tissues from patients with discogenic back pain are likely produced by IVD cells, and may play a key role in back pain.

Younger age, low birth weight and underlying disease are associated with severe RSVassociated ALRIs. Furthermore, severe RSV infections may be associated with a higher frequency of subsequent bronchitis, pneumonia and re-hospitalization in the following year.