The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term ...adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.
Though the early integration of mesenchymal stem cells (MSCs) into tumor-associated stroma of cancer has been demonstrated, the functional contributions and underlying mechanisms of these cells to ...tumor growth and angiogenesis remain to be clarified. Using a xenograft model, human colorectal cancer cells, MSCs, and their cell mixture were introduced to a subcutaneous site of immunodeficient mice. The tumor growth rate and angiogenesis of each transplantation was then compared. We demonstrate that a variety of colorectal cancer cells, when mixed with otherwise non-tumorigenic MSCs, increase the tumor growth rate and angiogenesis more than that when mixed with carcinoma-associated fibroblasts or normal colonic fibroblasts. The secretion of interleukin-6 (IL-6) from MSCs increases the secretion of endothelin-1 (ET-1) in cancer cells, which induces the activation of Akt and ERK in endothelial cells, thereby enhancing their capacities for recruitment and angiogenesis to tumor. The IL-6/ET-1/Akt or ERK pathway of tumor-stroma interaction can be targeted by an antibody against IL-6 or Lentiviral-mediated RNAi against IL-6 in MSCs, by inhibition or knockdown of ET-1 in cancer cells, or by inhibition of ERK and Akt in host endothelial cells. These demonstrate that attempts to interrupt the interaction of MSCs and cancer cells help to abrogate angiogenesis and inhibit tumor growth in tumors formed by cancer cells admixed with MSCs. These data demonstrate that the tumor microenvironment, namely, MSCs-secreted IL-6, may enrich the proangiognic factors secreted by cancer cells to increase angiogenesis and tumor growth and that targeting this interaction may lead to novel therapeutic and preventive strategies.
Thioamides antithyroid‐drugs (ATDs) are important in hyperthyroid disease management. Identification of the susceptibility locus of ATD‐induced agranulocytosis is important for clinical management. ...We performed a genome‐wide association study (GWAS) involving 20 patients with ATD‐induced agranulocytosis and 775 healthy controls. The top finding was further replicated. A single‐nucleotide polymorphism (SNP), rs185386680, showed the strongest association with ATD‐induced agranulocytosis in GWAS (odds ratio (OR) = 36.4; 95% confidence interval (CI) = 12.8–103.7; P = 1.3 × 10‐24) and replication (OR = 37; 95% CI = 3.7–367.4; P = 9.6 × 10‐7). HLA‐B*38:02:01 was in complete linkage disequilibrium with rs185386680. High‐resolution HLA typing confirmed that HLA‐B*38:02:01 was associated with carbimazole (CMZ)/methimazole (MMI)‐induced agranulocytosis (OR = 265.5; 95% CI = 27.9–2528.0; P = 2.5 × 10‐14), but not associated with propylthiouracil (PTU). The positive and negative predictive values of HLA‐B*38:02:01 in predicting CMZ/MMI‐induced agranulocytosis were 0.07 and 0.999. Approximately 211 cases need to be screened to prevent one case. Screening for the risk allele will be useful in preventing agranulocytosis in populations in which the frequency of the risk allele is high.
Fracture liaison services (FLS), implemented in different ways and countries, are reported to be a cost-effective or even a cost-saving secondary fracture prevention strategy. This presumed favorable ...cost-benefit relationship is encouraging and lends support to expanded implementation of FLS per International Osteoporosis Foundation Best Practice Standards. This study summarizes the economic impact and cost-effectiveness of FLS implemented to reduce subsequent fractures in individuals with osteoporosis. This systematic review identified studies reporting economic outcomes for FLS in osteoporotic patients aged 50 and older through a comprehensive search of MEDLINE, EMBASE, Cochrane Central, and PubMed of studies published January, 2000 to December, 2016. Grey literature (e.g., Google scholar, conference abstracts/posters) were also hand searched through February 2017. Two independent reviewers screened titles and abstracts and conducted full-text review on qualified articles. All disagreements were resolved by discussion between reviewers to reach consensus or by a third reviewer. In total, 23 qualified studies that evaluated the economic aspects of FLS were included: 16 cost-effectiveness studies, 2 cost-benefit analyses, and 5 studies of cost savings. Patient populations varied (prior fragility fracture, non-vertebral fracture, hip fracture, wrist fracture), and FLS strategies ranged from mail-based interventions to comprehensive nurse/physician-coordinated programs. Cost-effectiveness studies were conducted in Canada, Australia, USA, UK, Japan, Taiwan, and Sweden. FLS was cost-effective in comparisons with usual care or no treatment, regardless of the program intensity or the country in which the FLS was implemented (cost/QALY from $3023–$28,800 US dollars (USD) in Japan to $14,513–$112,877 USD in USA. Several studies documented cost savings. FLS, implemented in different ways and countries, are reported to be cost-effective or even cost-saving. This presumed favorable cost-benefit relationship is encouraging and lends support to expanded implementation of FLS per International Osteoporosis Foundation Best Practice Standards.
The discovery of circulating fetal nucleic acids in maternal plasma has opened up new possibilities for noninvasive prenatal diagnosis. MicroRNAs (miRNAs), a class of small RNAs, have been intensely ...investigated recently because of their important regulatory role in gene expression. Because nucleic acids of placental origin are released into maternal plasma, we hypothesized that miRNAs produced by the placenta would also be released into maternal plasma.
We systematically searched for placental miRNAs in maternal plasma to identify miRNAs that were at high concentrations in placentas compared with maternal blood cells and then investigated the stability and filterability of this novel class of pregnancy-associated markers in maternal plasma.
In a panel of TaqMan MicroRNA Assays available for 157 well-established miRNAs, 17 occurred at concentrations >10-fold higher in the placentas than in maternal blood cells and were undetectable in postdelivery maternal plasma. The 4 most abundant of these placental miRNAs (miR-141, miR-149, miR-299-5p, and miR-135b) were detectable in maternal plasma during pregnancy and showed reduced detection rates in postdelivery plasma. The plasma concentration of miR-141 increased as pregnancy progressed into the third trimester. Compared with mRNA encoded by CSH1 chorionic somatomammotropin hormone 1 (placental lactogen), miR-141 was even more stable in maternal plasma, and its concentration did not decrease after filtration.
We have demonstrated the existence of placental miRNAs in maternal plasma and provide some information on their stability and physical nature. These findings open up a new class of molecular markers for pregnancy monitoring.
This study explored biogeochemical processes controlling the distribution of mercury (Hg) species in two lagoons with different pollution and eutrophication conditions in southwestern Taiwan. The ...eutrophication and pollution levels were higher in the Dapeng Bay than in the Chiku Lagoon, engendering a higher particulate Hg concentration and enrichment factor in the Dapeng Bay. The concentration range of total dissolved Hg (HgTD) and reactive Hg (HgR) was comparable between the lagoons, but the concentration of particulate Hg (HgP) was higher in the Dapeng Bay. HgR and HgTD abundance was primarily controlled by the availability of dissolved oxygen (DO) and biological absorption. In addition to pollution (which elevated HgP concentration), biological absorption and/or adsorption rather than lithogenic processes more likely regulated the HgP concentration. The effect of Hg pollution may superimpose on that of DO on the distributions of HgR and HgTD and may enhance HgP formation in the Dapeng Bay.
•Dapeng Bay had higher eutrophication and Hg pollution levels than did Chiku Lagoon.•DO availability and biological absorption likely regulated HgR and HgTD distributions.•Hg pollution elevated and biological (not lithogenic) processes regulated HgP.•Hg pollution may superimpose on DO effects on HgR and HgTD distributions in Dapeng Bay.
Postprocedural infections by Mycobacterium abscessus complex are increasing worldwide, and the source and route of transmission are infrequently identified. Here the extension of a previous ...clustering of paediatric patients with surgical site infections due to a single strain of the subspecies M. massiliense is reported. The investigation was conducted at a 2200-bed teaching hospital in Taiwan and included microbial surveillance of the environment (water, air, equipment and supplies) and a case–control study. We performed molecular identification and typing of the isolates by a trilocus sequencing scheme, confirmed by multilocus sequencing typing and pulsed-field gel electrophoresis. We investigated 40 patients who developed postprocedure soft tissue or bloodstream infections by M. massiliense (TPE101) during a 3-year period. Thirty-eight patients were identified at hospital A, and one newborn and her mother were identified at hospital B (185 km from hospital A). A case–control study identified the association of invasive procedures (adjusted odds ratio, 9.13) and ultrasonography (adjusted odds ratio, 2.97) (both p <0.05) with acquiring the outbreak strain. Isolates from the cases and unopened bottles of ultrasound transmission gel were all of strain ST48 and indistinguishable or closely related by pulsed-field gel electrophoresis. After replacement of contaminated gel, no new cases were detected during 18 months' follow-up. This investigation identified the use of contaminated gel as the common source causing an outbreak on a larger scale than had been recognized. Our findings halted production by the manufacturer and prompted revision of hospital guidelines.
To understand carbon cycling in marginal seas better, particulate organic carbon (POC) concentrations, POC fluxes and primary production (PP) were measured in the East China Sea (ECS) in summer 2007. ...Higher concentrations of POC were observed in the inner shelf, and lower POC values were found in the outer shelf. Similar to POC concentrations, elevated uncorrected POC fluxes (720–7300 mg C m−2 d−1) were found in the inner shelf, and lower POC fluxes (80–150 mg C m−2 d−1) were in the outer shelf, respectively. PP values (~ 340–3380 mg C m−2 d−1) had analogous distribution patterns to POC fluxes, while some of PP values were significantly lower than POC fluxes, suggesting that contributions of resuspended particles to POC fluxes need to be appropriately corrected. A vertical mixing model was used to correct effects of bottom sediment resuspension, and the lowest and highest corrected POC fluxes were in the outer shelf (58 ± 33 mg C m−2 d−1) and the inner shelf (785 ± 438 mg C m−2 d−1), respectively. The corrected POC fluxes (486 to 785 mg C m−2 d−1) in the inner shelf could be the minimum value because we could not exactly distinguish the effect of POC flux from Changjiang influence with turbid waters. The results suggest that 27–93% of the POC flux in the ECS might be from the contribution of resuspension of bottom sediments rather than from the actual biogenic carbon sinking flux. While the vertical mixing model is not a perfect model to solve sediment resuspension because it ignores biological degradation of sinking particles, Changjiang plume (or terrestrial) inputs and lateral transport, it makes significant progress in both correcting the resuspension problem and in assessing a reasonable quantitative estimate of POC flux in a marginal sea.
We investigated the temporal progression of the clinical, radiological, and virological changes in a community outbreak of severe acute respiratory syndrome (SARS).
We followed up 75 patients for 3 ...weeks managed with a standard treatment protocol of ribavirin and corticosteroids, and assessed the pattern of clinical disease, viral load, risk factors for poor clinical outcome, and the usefulness of virological diagnostic methods.
Fever and pneumonia initially improved but 64 (85%) patients developed recurrent fever after a mean of 8.9 (SD 3.1) days, 55 (73%) had watery diarrhoea after 7.5 (2.3) days, 60 (80%) had radiological worsening after 7.4 (2.2) days, and respiratory symptoms worsened in 34 (45%) after 8.6 (3.0) days. In 34 (45%) patients, improvement of initial pulmonary lesions was associated with appearance of new radiological lesions at other sites. Nine (12%) patients developed spontaneous pneumomediastinum and 15 (20%) developed acute respiratory distress syndrome (ARDS) in week 3. Quantitative reverse-transcriptase (RT) PCR of nasopharyngeal aspirates in 14 patients (four with ARDS) showed peak viral load at day 10, and at day 15 a load lower than at admission. Age and chronic hepatitis B virus infection treated with lamivudine were independent significant risk factors for progression to ARDS (p=0.001). SARS-associated coronavirus in faeces was seen on RT-PCR in 65 (97%) of 67 patients at day 14. The mean time to seroconversion was 20 days.
The consistent clinical progression, shifting radiological infiltrates, and an inverted V viral-load profile suggest that worsening in week 2 is unrelated to uncontrolled viral replication but may be related to immunopathological damage.
Published online May 9, 2003 http://image.thelancet.com/extras/03art4432web.pdf
There has been a growing interest in realizing quantum simulators for physical systems where perturbative methods are ineffective. The scalability and flexibility of circuit quantum electrodynamics ...make it a promising platform for implementing various types of simulators, including lattice models of strongly coupled field theories. Here, we use a multimode superconducting parametric cavity as a hardware-efficient analog quantum simulator, realizing a lattice in synthetic dimensions with complex hopping interactions. The coupling graph, i.e., the realized model, can be programmed in situ. The complex-valued hopping interaction further allows us to simulate, for instance, gauge potentials and topological models. As a demonstration, we simulate a plaquette of the bosonic Creutz ladder. We characterize the lattice with scattering measurements, reconstructing the experimental Hamiltonian and observing important precursors of topological features including nonreciprocal transport and Aharonov-Bohm caging. This platform can be easily extended to larger lattices and different models involving other interactions.
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