Novel coronavirus (SARS-CoV-2) is found to cause a large outbreak started from Wuhan since December 2019 in China and SARS-CoV-2 infections have been reported with epidemiological linkage to China in ...25 countries until now. We isolated SARS-CoV-2 from the oropharyngeal sample obtained from the patient with the first laboratory-confirmed SARS-CoV-2 infection in Korea. Cytopathic effects of SARS-CoV-2 in the Vero cell cultures were confluent 3 days after the first blind passage of the sample. Coronavirus was confirmed with spherical particle having a fringe reminiscent of crown on transmission electron microscopy. Phylogenetic analyses of whole genome sequences showed that it clustered with other SARS-CoV-2 reported from Wuhan.
Background:
Active surveillance (AS) is an alternative to thyroidectomy for the management of low-risk papillary thyroid microcarcinoma (PTMC). However, prospective AS data collected from diverse ...populations are needed.
Methods:
This multicenter prospective cohort study enrolled patients from three referral hospitals in Korea. The participants were self-assigned into two groups, AS or immediate surgery. All patients underwent neck ultrasound every 6–12 months to monitor for disease progression. Progression under AS was evaluated by a criterion of tumor size increment by 3 mm in one dimension (3 mm), 2 mm in two dimensions (2 × 2 mm), new extrathyroidal extension (ETE), or new lymph node metastasis (LNM), and a composite outcome was defined using all four criteria.
Results:
A total of 1177 eligible patients with PTMC (919 female, 78.1%) with a median age of 48 years (range 19–87) were enrolled; 755 (64.1%) patients chose AS and 422 (35.9%) underwent surgery. Among 755 patients under AS, 706 (female 537, 76.1%) underwent at least two ultrasound examinations and were analyzed. Over a follow-up period of 41.4 months (standard deviation, 16.0), 163 AS patients (23.1%) underwent surgery. Progression defined by the composite outcome was observed in 9.6% (68/706) of patients, and the 2- and 5-year progression estimates were 5.3% and 14.2%, respectively. The observed progression rates were 5.8% (41/706) and 5.4% (38/706) as defined by tumor size enlargement by 3 mm and 2 × 2 mm, respectively, and 1.3% (9/706) and 0.4% (3/706) for new LNM and ETE, respectively. No distant metastases developed during AS. In multivariate logistic regression analysis examining variables associated with progression under AS, age at diagnosis <30 years (odds ratio OR, 2.86; 95% confidence interval CI, 1.10 − 7.45), male sex (OR, 2.48; 95% CI, 1.47 − 4.20), and tumor size ≥6 mm (OR, 1.89; 95% CI, 1.09 − 3.27) were independently significant.
Conclusions:
The progression of low-risk PTMC during AS in the Korean population was low, but slightly higher than previously reported in other populations. Risk factors for disease progression under AS include younger age, male sex, and larger tumor size.
Clinical trial registration:
Clinicaltrials.gov
NCT02938702.
The phase 2 LEO study showed that everolimus (EVE) plus letrozole (LET) with ovarian suppression increased progression‐free survival (PFS) in tamoxifen‐exposed premenopausal women with hormone ...receptor‐positive, HER2‐negative metastatic breast cancer with visceral metastases. Here we report final survival outcomes from the LEO study, and the results of exploratory analyses of bone turnover marker changes and bone‐specific progressive disease. Patients who were exposed to or progressed on tamoxifen as adjuvant/palliative treatments were randomly assigned (2:1) to the EVE (leuprorelin + LET + EVE, n = 92) or LET (leuprorelin + LET, n = 45) arm. In a median 51‐months of follow‐up, the median PFS was 17.5 and 13.8 months in the EVE and LET arms, respectively (P = .245). Patients in the EVE arm with baseline visceral (median PFS 16.4 vs 9.5 months, P = .040) and bone (median PFS 17.1 vs 10.9, P = .003) metastases had greater PFS compared to the LET arm. No differences in overall survival (OS) were observed (median OS, 48.3 vs 50.8 months, P = .948). The 1‐year cumulative incidences of bone‐specific disease progression were 6.0% and 23.4% in the EVE and LET arms, respectively (hazard ratio 0.26, P < .001). Bone turnover markers at 6 and 12 weeks after treatment decreased in the EVE arm but were increased or stationary in the LET arm. Skeletal‐related events occurred in 6.5% and 11.1% of patients in the EVE and LET arms, respectively. EVE + LET with ovarian suppression prolonged PFS in patients with baseline visceral or bone metastases and offered bone‐protective effects in the overall study population. However, these clinical benefits did not translate into an OS benefit.
What's new?
In the phase 2 LEO study, women with hormone receptor‐positive, human epidermal growth factor receptor 2‐negative metastatic breast cancer with visceral metastases who were previously treated with tamoxifen, experienced significant improvements in progression‐free survival following combination therapy with the protein kinase inhibitor everolimus and the aromatase inhibitor letrozole. This report describes final survival outcomes from the LEO study. Patients with visceral or bone metastases treated with combined leuprorelin, letrozole, and everolimus survived longer with progression‐free disease compared to women who received leuprorelin and letrozole. Regimens employing everolimus were associated with reductions in bone turnover, bone‐specific disease progression, and skeletal‐related events, suggesting a role for everolimus in bone protection.
The papain-like protease (PLpro), which controls replication of the severe acute respiratory syndrome coronavirus (SARS-CoV), has been identified as a potential drug target for the treatment of SARS. ...An intensive hunt for effective anti-SARS drugs has been undertaken by screening for natural product inhibitors that target SARS-CoV PLpro. In this study, diarylheptanoids 1-9 were isolated from Alnus japonica, and the inhibitory activities of these compounds against PLpro were determined. Of the isolated diarylheptanoids, hirsutenone (2) showed the most potent PLpro inhibitory activity, with an inhibitory concentration (IC50) value of 4.1 µM. Structure-activity analysis showed that catechol and α,β-unsaturated carbonyl moiety in the molecule were the key requirement for SARS-CoV cysteine protease inhibition.
Increases in oxidative stress are thought to be associated with the development of osteoarthritis (OA). Eupatilin, one of the major compounds present in artemisia species, was shown to have both ...anti-oxidative and anti-inflammatory properties. Here, we investigated the in vivo effects of eupatilin on pain severity and cartilage degradation in an experimental rat model of OA, along with the mechanisms of action underlying these effects. Experimental OA was induced via an intra-articular injection of monosodium iodoacetate (MIA), with oral administration of eupatilin initiated on the day of MIA injection. Pain was assessed by measuring the paw withdrawal latency and threshold. Cartilage destruction was analyzed macroscopically and histomorphologically. The effects of eupatilin on mRNA expression were investigated in interleukin-1β (IL-1β)-stimulated human OA chondrocytes. Eupatilin treatment exhibited clear antinociceptive effects, along with an attenuation of cartilage degradation in OA rats. Additionally, the number of osteoclasts present in the subchondral bone region was significantly decreased following eupatilin treatment. Eupatilin reduced the expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), nitrotyrosine and inducible nitric oxide synthase (iNOS) in cartilage. mRNA levels of matrix metalloproteinase-3 (MMP-3), MMP13, and a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5) were reduced in IL-1β-stimulated human OA chondrocytes, while tissue inhibitor of metalloproteinases-1 (TIMP-1) was induced. Phosphorylated protein levels of the c-jun N-terminal kinase (JNK) was reduced by eupatilin. Taken together, these results suggest that eupatilin suppresses oxidative damage and reciprocally enhances extracellular matrix production in articular chondrocytes, making eupatilin a promising therapeutic option for the treatment of OA.
Few studies have used a longitudinal approach to describe the immune response to SARS-CoV-2 infection. Here, we perform single-cell RNA sequencing of bronchoalveolar lavage fluid cells longitudinally ...obtained from SARS-CoV-2-infected ferrets. Landscape analysis of the lung immune microenvironment shows distinct changes in cell proportions and characteristics compared to uninfected control, at 2 and 5 days post-infection (dpi). Macrophages are classified into 10 distinct subpopulations with transcriptome changes among monocyte-derived infiltrating macrophages and differentiated M1/M2 macrophages, notably at 2 dpi. Moreover, trajectory analysis reveals gene expression changes from monocyte-derived infiltrating macrophages toward M1 or M2 macrophages and identifies a macrophage subpopulation that has rapidly undergone SARS-CoV-2-mediated activation of inflammatory responses. Finally, we find that M1 or M2 macrophages show distinct patterns of gene modules downregulated by immune-modulatory drugs. Overall, these results elucidate fundamental aspects of the immune response dynamics provoked by SARS-CoV-2 infection.
The selection of the location of a biomass plant is a critical concern because biomass feedstocks are geographically and spatially dispersed. Geographic Information System-Multi-Criteria Decision ...Analysis (GIS-MCDA) techniques are powerful methods that have been applied to various disciplines using suitable criteria. These methods can be used to solve power planning problems, such as determining the optimal locations of biomass plants in the context of renewable energy. In response to the promotion of renewable energy in European strategy, Extremadura (Spain) is boosting energy generation from biomass as an alternative to traditional generation to protect the environment. This study presents a combined application of GIS-MCDA and the Fuzzy-DEcision-MAking Trial and Evaluation Laboratory (F-DEMATEL) technique to identify suitable and favorable sites for biomass facilities in terms of long-term sustainability. The main criteria established in this approach are outlined, evaluated, weighted and allocated to three criteria groups: environmental, geophysical and socio-economic groups. In the F-DEMATEL participatory method, constraints and their weight coefficients, with regard to their influence, are calculated. The most suitable locations are obtained after applying the Weighted Linear Combination (WLC) method. In the final stage of the decision-making problem, a sensitivity analysis of the criteria set is conducted, and the weights are determined for four implementation strategies. The model is applied in a case study of Extremadura where forest and agriculture are the typical land uses. The results of the F-DEMATEL/GIS-MCDA analysis suggest that the optimal sites for the locations of biomass plants are situated near forests and in zones with low transport costs, which comprise only 9.247% (Sh) of the total study area. Currently, five plants are installed in this area; however, they are not located in the most suitable areas (Sh). The most influential criteria of the model are the vegetation cover, agricultural area, transport cost and potential demand criteria. This methodology can be used in other studies to verify suitable locations for biomass plants in areas with similar geographical and spatial characteristics and available spatial data. Additionally, the proposed method of renewable energy policy planning can be applied to decision-making problems in the private sector and at various government levels.
Display omitted
•An integrated model for determining the locations of sustainable biomass plants is developed.•The operational method considers energy and land use issues based on spatial assessment.•The five biomass plants in the case study area are not located in the most suitable areas.•A sensitivity analysis of the modified weight coefficients of criteria demonstrates the high stability of the model.•The optimal locations for biomass plants are near forested areas with low transport costs.
Early intervention using dietary supplements may be effective in alleviating cognitive impairment among individuals with mild cognitive impairment (MCI). This study investigated the efficacy and ...safety of
C29-fermented soybean (DW2009) as a nutritional supplement for cognitive enhancement. One hundred individuals with MCI were randomly assigned to take DW2009 (800 mg/day,
= 50) or placebo (800 mg/day,
= 50) for 12 weeks. The primary outcome measure was change in the composite score of cognitive functions related to memory and attention, measured by computerized neurocognitive function tests. Associations between changes in serum brain-derived neurotrophic factor (BDNF) levels and cognitive performance for each treatment group were evaluated. Compared to the placebo group, the DW2009 group showed greater improvements in the combined cognitive functions (
= 2.36,
for interaction = 0.02), especially in the attention domain (
= 2.34,
for interaction = 0.02). Cognitive improvement was associated with increased serum BDNF levels after consumption of DW2009 (
= 2.83,
= 0.007). The results of this clinical trial suggest that DW2009 can be safely administered to enhance cognitive function in individuals with MCI. Increased serum BDNF levels after administering DW2009 may provide preliminary insight into the underlying effects of cognitive improvement, which suggests the importance of the gut-brain axis in ameliorating cognitive deficits in MCI.
This study investigated the laxative effects of phlorotannins (Pt) derived from
(
) on chronic constipation by evaluating alterations in stool parameters, gastrointestinal motility, histopathological ...structure, mucin secretion, gastrointestinal hormones, muscarinic cholinergic regulation, and fecal microbiota in SD rats with loperamide (Lop)-induced constipation subjected to Pt treatment. Stool-related parameters (including stool number, weight, and water contents), gastrointestinal motility, and length of intestine were significantly enhanced in the Lop+Pt-treated group as compared to the Lop+Vehicle-treated group. A similar recovery was detected in the histopathological and cytological structure of the mid-colon of Lop+Pt-treated rats, although the level of mucin secretion remained constant. Moreover, rats with Lop-induced constipation subjected to Pt treatment showed significant improvements in water channel expression, gastrointestinal hormone secretions, and expression of muscarinic acetylcholine receptors M2/M3 (mAChRs M2/M3) and their mediators of muscarinic cholinergic regulation. Furthermore, the Lop+Pt-treated group showed a significant recovery of
,
,
, and
families in fecal microbiota. Taken together, these results provide the first evidence that exposure of SD rats with Lop-induced constipation to Pt improves the constipation phenotype through the regulation of membrane water channel expression, GI hormones, the mAChR signaling pathway, and fecal microbiota.
Abstract
Context
The long-term quality of life (QoL) in patients with low-risk papillary thyroid microcarcinoma (PTMC) underwent active surveillance (AS) and immediate surgery is unclear.
Objective
...The aim of this study was to investigate the effect of initial treatment choice on 2-year QoL in patients with low-risk PTMC
Design, Setting, and Participants
We analyzed 2652 QoL surveys from 1055 subjects enrolled in ongoing multicenter prospective cohort study on active surveillance of PTMC, in which the median follow-up duration was 24.4 months.
Major Outcome Measure
We evaluated QoL of patients with low-risk PTMC according to their treatment modality using generalized estimating equation.
Results
Six hundred and seventy-four subjects (male = 161; mean age = 48.8 ± 11.9 years) with low-risk PTMC chose AS while 381 subjects (male = 75; mean age = 45.7 ± 10.4 years) chose immediate surgery, including lobectomy/isthmusectomy (L/I) and total thyroidectomy (TT). Among the 817 subjects who completed baseline QoL surveys, 2-year QoL was good in order of AS (n = 500), L/I (n = 238), and TT (n = 79) groups after adjustment for age, sex, baseline tumor size, and baseline QoL scores. Among the 101 subjects who changed their treatment from AS to surgery during the follow-up period, 35 subjects who changed treatment due to disease progression had better QoL than 66 subjects who had no disease progression.
Conclusions
This study identified QoL as a major issue in choosing an initial treatment of low-risk PTMC and highlighted the possibility of using AS as the primary treatment.
PDF
