Mucopolysaccharidoses (MPS) are lysosomal storage diseases in which mutations of genes encoding for lysosomal enzymes cause defects in the degradation of glycosaminoglycans (GAGs). The accumulation ...of GAGs in lysosomes results in cellular dysfunction and clinical abnormalities. The early initiation of enzyme replacement therapy (ERT) can slow or prevent the development of severe clinical manifestations. MPS I and II newborn screening has been available in Taiwan since August 2015. Infants who failed the recheck at recall were referred to MacKay Memorial Hospital for a detailed confirmatory diagnosis.
From August 2015 to November 2017, 294,196 and 153,032 infants were screened using tandem mass spectrometry for MPS I and MPS II, respectively. Of these infants, 84 suspected cases (eight for MPS I; 76 for MPS II) were referred for confirmation. Urinary first-line biochemistry examinations were performed first, including urinary GAG quantification, two-dimensional electrophoresis, and tandem mass spectrometry assay for predominant disaccharides derived from GAGs. If the results were positive, a confirmative diagnosis was made according to the results of leukocyte enzymatic assay and molecular DNA analysis. Leukocyte pellets were isolated from EDTA blood and used for fluorescent α-iduronidase (IDUA) or iduronate-2-sulfatase (IDS) enzymatic assay. DNA sequencing analysis was also performed.
Normal IDS and IDUA enzyme activities were found in most of the referred cases except for four who were strongly suspected of having MPS I and three who were strongly suspected of having MPS II. Of these infants, three with novel mutations of the IDS gene (c.817C > T, c.1025A > G, and c.311A > T) and four with two missense mutations of the IDUA gene (C.300-3C > G, c.1874A > C; c.1037 T > G, c.1091C > T) showed significant deficiencies in IDS and IDUA enzyme activities (< 5% of mean normal activity), respectively. Urinary dermatan sulfate and heparan sulfate quantitative analyses by tandem mass spectrometry also demonstrated significant elevations. The prevalence rates of MPS I and MPS II in Taiwan were 1.35 and 1.96 per 100,000 live births, respectively.
The early initiation of ERT for MPS can result in better clinical outcomes. An early confirmatory diagnosis increases the probability of receiving appropriate medical care such as ERT quickly enough to avoid irreversible manifestations. All high risk infants identified in this study so far remain asymptomatic and are presumed to be affected with the attenuated disease variants.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Drug survival of biologics represents their real-world effectiveness and safety. We conducted a meta-analysis of real-world evidence on the drug survival of biologics in treating psoriasis. We ...searched the PubMed, CENTRAL, and EMBASE databases from inception to 7th October 2017 for studies reporting the annual drug survival for at least 1 year. Two authors independently screened and selected relevant studies, and assessed their risk of bias. A third author was available for arbitrating discrepancies. We conducted a random-effects model meta-analysis to obtain the respective pooled drug survival from year 1 to 4. We conducted subgroup analysis on biologic-naïve subjects, discontinuation for loss of efficacy and adverse effects. We included 37 studies with 32,631 subjects. The drug survival for all biologics decreased with time, dropping from 66% at year 1 to 41% at year 4 for etanercept, from 69% to 47% for adalimumab, from 61% to 42% for infliximab, and from 82% to 56% for ustekinumab. Ustekinumab was associated with the highest drug survival in all and biologic-naïve subjects. Etanercept was associated with the lowest drug survival and was most commonly discontinued for loss of efficacy. Infliximab was most frequently associated with discontinuation for adverse effects. Clinicians may use this study as a reference in treating psoriasis.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
Scarlet fever has resurged in China starting in 2011, and the environment is one of the potential reasons. Nationwide data on 655,039 scarlet fever cases and six air pollutants were ...retrieved. Exposure risks were evaluated by multivariate distributed lag nonlinear models and a meta-regression model. We show that the average incidence in 2011–2018 was twice that in 2004–2010 RR = 2.30 (4.40 vs. 1.91), 95% CI: 2.29–2.31; p < 0.001 and generally lower in the summer and winter holiday (p = 0.005). A low to moderate correlation was seen between scarlet fever and monthly NO
2
(r = 0.21) and O
3
(r = 0.11). A 10 μg/m
3
increase of NO
2
and O
3
was significantly associated with scarlet fever, with a cumulative RR of 1.06 (95% CI: 1.02–1.10) and 1.04 (95% CI: 1.01–1.07), respectively, at a lag of 0 to 15 months. In conclusion, long-term exposure to ambient NO
2
and O
3
may be associated with an increased risk of scarlet fever incidence, but direct causality is not established.
For the application of organic light-emitting diodes (OLEDs) in lighting and panels, the basic requirement is to include a full spectrum color range. Compared with the development of blue and green ...luminophores in thermally activated delayed fluorescence (TADF) technology, the progress of orange-to-red materials is slow and needs further investigation. In this study, three diboron compound-based materials, dPhADBA, dmAcDBA, and SpAcDBA, were designed and synthesized by nucleophilic arylation of three amine donors on 9,10-diboraanthracene (DBA) in a two-step reaction. With increasing electron-donating ability, they show orange-to-red emission with TADF characteristics. The electroluminescence of these diboron compounds exhibits emissions λmax at 613, 583, and 567 nm for dPhADBA, dmAcDBA, and SpAcDBA, respectively. It is noteworthy that the rod-like D-A-D structures can achieve high horizontal ratios (84–86%) and outstanding device performance for orange-to-red TADF OLEDs: the highest external quantum efficiencies for dPhADBA, dmAcDBA, and SpAcDBA are 11.1 ± 0.5, 24.9 ± 0.5, and 30.0 ± 0.8%, respectively. Therefore, these diboron-based molecules offer a promising avenue for the design of orange-to-red TADF emitters and the development of highly efficient orange-to-red OLEDs.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
Selective autophagy is a defense mechanism by which foreign pathogens and abnormal substances are processed to maintain cellular homeostasis. Sequestosome 1 (SQSTM1)/p62, a vital selective autophagy ...receptor, recruits ubiquitinated cargo to form autophagosomes for lysosomal degradation. Nab-PTX is an albumin-bound paclitaxel nanoparticle used in clinical cancer therapy. However, the role of SQSTM1 in regulating the delivery and efficacy of nanodrugs remains unclear. Here we showed that SQSTM1 plays a crucial role in Nab-PTX drug delivery and efficacy in human lung and colorectal cancers. Nab-PTX induces SQSTM1 phosphorylation at Ser403, which facilitates its incorporation into the selective autophagy of nanoparticles, known as nanoparticulophagy. Nab-PTX increased LC3-II protein expression, which triggered autophagosome formation. SQSTM1 enhanced Nab-PTX recognition to form autophagosomes, which were delivered to lysosomes for albumin degradation, thereby releasing PTX to induce mitotic catastrophe and apoptosis. Knockout of SQSTM1 downregulated Nab-PTX-induced mitotic catastrophe, apoptosis, and tumor inhibition in vitro and in vivo and inhibited Nab-PTX-induced caspase 3 activation via a p53-independent pathway. Ectopic expression of SQSTM1 by transfection of an SQSTM1-GFP vector restored the drug efficacy of Nab-PTX. Importantly, SQSTM1 is highly expressed in advanced lung and colorectal tumors and is associated with poor overall survival in clinical patients. Targeting SQSTM1 may provide an important strategy to improve nanodrug efficacy in clinical cancer therapy. This study demonstrates the enhanced efficacy of Nab-PTX for human lung and colorectal cancers via SQSTM1-mediated nanodrug delivery.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
The risk of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in primary Sjogren syndrome (pSS) has rarely been explored. To explore the association between BRONJ and pSS, we conducted a ...population-based propensity-score-matched cohort study using Taiwan's National Health Insurance Research Database, including pSS patients receiving antiosteoporotic therapy and patients without pSS receiving antiosteoporotic therapy. A 1:4 matched-pair cohort based on propensity score was created. The stratified Cox proportional hazards model compared the risk of BRONJ in the pSS and non-pSS groups. In the study, 23,280 pSS patients and 28,712,152 controls were enrolled. After matching, 348 patients with pSS receiving antiosteoporotic drugs and 50,145 without pSS receiving antiosteoporotic drugs were included for analysis. The risk of developing BRONJ was 1.96 times higher in pSS patients compared with non-pSS patients after adjustment for age, sex, and comorbidities. No dose-response effect was observed in the bisphosphonate-treated pSS cohorts, documented as the cumulative defined daily doses of either < 224 or ≥ 224 (hazard ratio HR: 2.407, 95% confidence interval CI 1.412-7.790; HR: 2.143, 95% CI 1.046-4.393, respectively) increased risk of developing osteonecrosis of the jaw. In conclusion, the risk of BRONJ is significantly higher in patients with pSS compared with the general population.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Multidrug resistance (MDR) is a major challenge in cancer chemotherapy. Nanoparticles as drug delivery systems (DDSs) show promise for MDR cancer therapy. However, current DDSs require sophisticated ...design and construction based on xenogeneic nanomaterials, evoking feasibility and biocompatibility concerns. Herein, a simple but versatile biological DDS (bDDS) composed of human red blood cell (RBC)-derived vesicles (RDVs) with excellent biocompatibility was surface-linked with doxorubicin (Dox) using glutaraldehyde (glu) to form Dox-gluRDVs that remarkably suppressed MDR in uterine sarcoma through a lysosomal-mitochondrial axis-dependent cell death mechanism. Dox-gluRDVs can efficiently deliver and accumulate Dox in lysosomes, bypassing drug efflux transporters and facilitating cellular uptake and retention of Dox in drug-resistant MES-SA/Dx5 cells. The transfer of lysosomal calcium to the mitochondria during mitochondria-lysosome contact due to lysosomal Dox accumulation may result in mitochondrial ROS overproduction, mitochondrial membrane potential loss, and activation of apoptotic signaling for the superior anti-MDR activity of Dox-gluRDVs in vitro and in vivo. This work highlights the great promise of RDVs to serve as a bDDS of Dox to overcome MDR cancers but also opens up a reliable strategy for lysosomal-mitochondrial axis-dependent cell death for fighting against other inoperable cancers.
Display omitted
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
The success of digital replantation is highly dependent on the patency of the repaired vessels after microvascular anastomosis. Antithrombotic agents are frequently used for preventing ...vascular occlusion. Low molecular weight heparin (LMWH) has been reported to be as effective as unfractionated heparin (UFH) in peripheral vascular surgery, but with fewer adverse effects. Its benefit in microvascular surgery such as digital replantation is unclear. This is an update of the review first published in 2013.
Objectives
To assess if treatment with subcutaneous LMWH improves the salvage rate of the digits in patients with digital replantation after traumatic amputation.
Search methods
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, AMED and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers, to 17 March 2020. The authors searched PubMed, China National Knowledge Infrastructure (CNKI) and Chinese Electronic Periodical Services (CEPS) on 17 March 2020 and sought additional trials from reference lists of relevant publications.
Selection criteria
We included randomised or quasi‐randomised controlled trials comparing treatment with LMWH versus any other treatment in participants who received digital replantation following traumatic digital amputation.
Data collection and analysis
Two review authors (PL, CC) independently extracted data and assessed the risk of bias of the included trials using Cochrane's 'Risk of bias' tool. Disagreements were resolved by discussion. We assessed the certainty of evidence using the GRADE approach.
Main results
We included two new randomised trials in this update, bringing the total number of included trials to four. They included a total of 258 participants, with at least 273 digits, from hospitals in China. Three studies compared LMWH versus UFH, and one compared LMWH versus no LMWH. The mean age of participants ranged from 24.5 to 37.6 years. In the studies reporting the sex of participants, there were a total of 145 men and 59 women. The certainty of the evidence was downgraded to low or very low because all studies were at high risk of performance or reporting bias (or both) and there was imprecision in the results due to the small numbers of participants.
The three studies comparing LMWH versus UFH reported the success rate of replantation using different units of analysis (participant or digit), so we were unable to combine data from all three studies (one study reported results for both participants and digits). No evidence of a benefit in success of replantation was seen in the LMWH group when compared with UFH, regardless of whether the outcomes were reported by number of participants (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.87 to 1.10; 130 participants, 2 studies; very low‐certainty evidence); or by number of digits (RR 0.97, 95% CI 0.90 to 1.04; 200 digits, 2 studies; low‐certainty evidence). No studies reported the incidence of compromised microcirculation requiring surgical or non‐surgical therapy, or any systemic/other causes of microvascular insufficiency. There was no evidence of a clear difference between the LMWH and UFH groups in occurrence of arterial occlusion (RR 1.08, 95% CI 0.16 to 7.10; 54 participants, 1 study; very low‐certainty evidence) or venous occlusion (RR 0.81, 95% CI 0.20 to 3.27; 54 participants, 1 study; very low‐certainty evidence). Two studies reported adverse effects. The LMWH and UFH groups showed no evidence of a difference in wound bleeding (RR 0.53, 95% CI 0.23 to 1.23; 130 participants, 2 studies; low‐certainty evidence), haematuria (RR 0.43, 95% CI 0.09 to 2.11; 130 participants, 2 studies; very low‐certainty evidence), ecchymoses (RR 0.82, 95% CI 0.21 to 3.19; 130 participants, 2 studies; very low‐certainty evidence), epistaxis (RR 0.27, 95% CI 0.03 to 2.32; 130 participants, 2 studies; very low‐certainty evidence), gingival bleeding (RR 0.18, 95% CI 0.02 to 1.43; 130 participants, 2 studies; very low‐certainty evidence), and faecal occult blood (RR 0.27, 95% CI 0.03 to 2.31; 130 participants, 2 studies; very low‐certainty evidence). We could not pool data on coagulation abnormalities as varying definitions and tests were used in the three studies.
One study compared LMWH versus no LMWH. The success rate of replantation, when analysed by digits, was reported as 91.2% success in the LMWH group and 82.1% in the control group (RR 1.11, 95% CI 0.93 to 1.33; 73 digits, 1 study; very low‐certainty evidence). Compromised microcirculation requiring surgical re‐exploration, analysed by digits, was 11.8% in the LMWH group and 17.9% in the control group (RR 0.86, 95% CI 0.21 to 3.58; 73 digits, 1 study; very low‐certainty evidence). Compromised microcirculation requiring incision occurred in five out of 34 digits (14.7%) in the LMWH group and eight out of 39 digits (20.5%) in the control group (RR 0.72, 95% CI 0.26 to 1.98; 73 digits; very low‐certainty evidence). Microvascular insufficiency due to arterial occlusion, analysed by digits, was 11.8% in the LMWH group and 17.9% in the control group (RR 0.66, 95% CI 0.21 to 2.05; 73 digits, 1 study; very low‐certainty evidence), and venous occlusion was 14.7% in the LMWH group and 20.5% in the control (RR 0.72, 95% CI 0.26 to 1.98; 73 digits, 1 study; very low‐certainty evidence). The study did not report complications or adverse effects.
Authors' conclusions
There is currently low to very low‐certainty evidence, based on four RCTs, suggesting no evidence of a benefit from LMWH when compared to UFH on the success rates of replantation or affect microvascular insufficiency due to vessel occlusion (analysed by digit or participant). LMWH had similar success rates of replantation; and the incidence rate of venous and arterial microvascular insufficiency showed no evidence of a difference between groups when LMWH was compared to no LMWH (analysed by digit). Similar rates of complications and adverse effects were seen between UFH and LMWH. There was insufficient evidence to draw conclusions on any effect on coagulation when comparing LMWH to UFH or no LMWH. The certainty of the evidence was downgraded due to performance and reporting bias, as well as imprecision in the results. Further adequately powered studies are warranted to provide high‐certainty evidence.
This study pursues a better understanding of consumer well-being in online medical cosmetics communities by investigating the antecedents of well-being and moderating influence of community norms. A ...total valid sample of 484 respondents was collected from 2 popular medical cosmetics discussion platforms. A partial least squares analysis was used to validate the research model. Emotional support, informational support, and sense of belonging were important predictors of well-being. Among these 3 antecedents, emotional support showed the strongest influence on consumer well-being. Sense of belonging was significantly and positively influenced by emotional support and reciprocity, and hence plays a pivotal role in mediating the effects of emotional support and reciprocity on well-being. However, informational support does not appear to significantly influence sense of belonging. Members’ compliance with community norms positively moderates the influence of sense of belonging on well-being. This study contributes to the literature on realizing members’ social behaviors specifically in virtual medical cosmetics communities and provides insights for the management of online communities.
A simplified seismic evaluation method using capacity‐based inelastic displacement spectra is proposed for reinforced concrete (RC) bridges. The proposed method can not only estimate the maximum ...displacements of bridges, but can also discriminate the damage indices between the bridge columns, where the Park and Ang's damage index (DI) is considered a promising performance indicator due to its good relationship with the strength capacity state and actual visual damage condition of the bridge column regardless of the imposed loading history. To realize the accuracy and reliability of the proposed method, a hypothetical case study bridge was constructed and analyzed using various structural analysis programs and seismic evaluation methods. It was found that the proposed method can receive satisfactory estimates of the maximum displacement and DI for both far‐field and near‐fault ground motions when compared to the nonlinear time history analysis results of the bridge. In contrast, the AASHTO's and Caltrans’ methods cannot reflect the response amplification effects caused by the frequency‐content characteristics of near‐fault ground motions and would therefore significantly underestimate the inelastic responses of bridges. When applying the proposed method to bridges having unequal‐height columns and subjected to longitudinal seismic actions, it was found that for the short column of the bridge, the AASHTO's regularity criteria (maximum bent/pier stiffness ratio of 4 for the three‐span case study bridge) would lead to a DI of approximately 3.5 times that of the tall column, resulting in significant damage localization and, hence, decreasing the overall lateral deformation capacity of the bridge.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
PDF
