HLA-II immunopeptidome profiling and deep learning reveal features of antigenicity to inform antigen discovery.

CD4+ T cell responses are exquisitely antigen specific and directed toward peptide epitopes displayed by human leukocyte antigen class II (HLA-II) on antigen-presenting cells. Underrepresentation of diverse alleles in ligand databases and an incomplete understanding of factors affecting antigen presentation in vivo have limited progress in defining principles of peptide immunogenicity. Here, we employed monoallelic immunopeptidomics to identify 358,024 HLA-II binders, with a particular focus on HLA-DQ and HLA-DP. We uncovered peptide-binding patterns across a spectrum of binding affinities and enrichment of structural antigen features. These aspects underpinned the development of context-aware predictor of T cell antigens (CAPTAn), a deep learning model that predicts peptide antigens based on their affinity to HLA-II and full sequence of their source proteins. CAPTAn was instrumental in discovering prevalent T cell epitopes from bacteria in the human microbiome and a pan-variant epitope from SARS-CoV-2. Together CAPTAn and associated datasets present a resource for antigen discovery and the unraveling genetic associations of HLA alleles with immunopathologies.

Enhancement of NETosis by ACE2-cross-reactive anti-SARS-CoV-2 RBD antibodies in patients with COVID-19.

BACKGROUND: High levels of neutrophil extracellular trap (NET) formation or NETosis and autoantibodies are related to poor prognosis and disease severity of COVID-19 patients. Human angiotensin-converting enzyme 2 (ACE2) cross-reactive anti-severe acute respiratory syndrome coronavirus 2 spike protein receptor-binding domain (SARS-CoV-2 RBD) antibodies (CR Abs) have been reported as one of the sources of anti-ACE2 autoantibodies. However, the pathological implications of CR Abs in NET formation remain unknown. METHODS: In this study, we first assessed the presence of CR Abs in the sera of COVID-19 patients with different severity by serological analysis. Sera and purified IgG from CR Abs positive COVID-19 patients as well as a mouse monoclonal Ab (mAb 127) that can recognize both ACE2 and the RBD were tested for their influence on NETosis and the possible mechanisms involved were studied. RESULTS: An association between CR Abs levels and the severity of COVID-19 in 120 patients was found. The CR Abs-positive sera and IgG from severe COVID-19 patients and mAb 127 significantly activated human leukocytes and triggered NETosis, in the presence of RBD. This NETosis, triggered by the coexistence of CR Abs and RBD, activated thrombus-related cells but was abolished when the interaction between CR Abs and ACE2 or Fc receptors was disrupted. We also revealed that CR Abs-induced NETosis was suppressed in the presence of recombinant ACE2 or the Src family kinase inhibitor, dasatinib. Furthermore, we found that COVID-19 vaccination not only reduced COVID-19 severity but also prevented the production of CR Abs after SARS-CoV-2 infection. CONCLUSIONS: Our findings provide possible pathogenic effects of CR Abs in exacerbating COVID-19 by enhancing NETosis, highlighting ACE2 and dasatinib as potential treatments, and supporting the benefit of vaccination in reducing disease severity and CR Abs production in COVID-19 patients.

Prompt antimicrobial therapy and source control on survival and defervescence of adults with bacteraemia in the emergency department: the faster, the better.

BACKGROUND: Bacteraemia is a critical condition that generally leads to substantial morbidity and mortality. It is unclear whether delayed antimicrobial therapy (and/or source control) has a prognostic or defervescence effect on patients with source-control-required (ScR) or unrequired (ScU) bacteraemia. METHODS: The multicenter cohort included treatment-naïve adults with bacteraemia in the emergency department. Clinical information was retrospectively obtained and etiologic pathogens were prospectively restored to accurately determine the time-to-appropriate antibiotic (TtAa). The association between TtAa or time-to-source control (TtSc, for ScR bacteraemia) and 30-day crude mortality or delayed defervescence were respectively studied by adjusting independent determinants of mortality or delayed defervescence, recognised by a logistic regression model. RESULTS: Of the total 5477 patients, each hour of TtAa delay was associated with an average increase of 0.2% (adjusted odds ratio [AOR], 1.002; P < 0.001) and 0.3% (AOR 1.003; P < 0.001) in mortality rates for patients having ScU (3953 patients) and ScR (1524) bacteraemia, respectively. Notably, these AORs were augmented to 0.4% and 0.5% for critically ill individuals. For patients experiencing ScR bacteraemia, each hour of TtSc delay was significantly associated with an average increase of 0.31% and 0.33% in mortality rates for overall and critically ill individuals, respectively. For febrile patients, each additional hour of TtAa was significantly associated with an average 0.2% and 0.3% increase in the proportion of delayed defervescence for ScU (3085 patients) and ScR (1266) bacteraemia, respectively, and 0.5% and 0.9% for critically ill individuals. For 1266 febrile patients with ScR bacteraemia, each hour of TtSc delay respectively was significantly associated with an average increase of 0.3% and 0.4% in mortality rates for the overall population and those with critical illness. CONCLUSIONS: Regardless of the need for source control in cases of bacteraemia, there seems to be a significant association between the prompt administration of appropriate antimicrobials and both a favourable prognosis and rapid defervescence, particularly among critically ill patients. For ScR bacteraemia, delayed source control has been identified as a determinant of unfavourable prognosis and delayed defervescence. Moreover, this association with patient survival and the speed of defervescence appears to be augmented among critically ill patients.

Residual risk of cardiovascular complications in statin-using patients with type 2 diabetes: the Taiwan Diabetes Registry Study.

BACKGROUND: The residual risks of atherosclerotic cardiovascular disease in statin-treated patients with diabetes remain unclear. This study was conducted to identify factors associated with these residual risks in patients with no prior vascular event. METHODS: Data on 683 statin-using patients with type 2 diabetes mellitus (T2DM) from the Taiwan Diabetes Registry were used in this study. Patients aged < 25 or > 65 years at the time of diabetes diagnosis and those with diabetes durations ≥ 20 years were excluded. The United Kingdom Prospective Diabetes Study risk engine (version 2.01; https://www.dtu.ox.ac.uk/riskengine/ ) was used to calculate 10-year residual nonfatal and fatal coronary heart disease (CHD) and stroke risks. Associations of these risks with physical and biochemical variables, including medication use and comorbidity, were examined. RESULTS: The 10-year risks of nonfatal CHD in oral anti-diabetic drug (OAD), insulin and OAD plus insulin groups were 11.8%, 16.0%, and 16.8%, respectively. The 10-year risks of nonfatal stroke in OAD, insulin and OAD plus insulin groups were 3.0%, 3.4%, and 4.3%, respectively. In the multivariate model, chronic kidney disease (CKD), neuropathy, insulin use, calcium-channel blocker (CCB) use, higher body mass indices (BMI), low-density lipoprotein (LDL), fasting glucose, log-triglyceride (TG), and log-alanine transaminase (ALT) levels were associated with an increased CHD risk. The residual risk of stroke was associated with CKD, neuropathy, CCB use, and lower LDL cholesterol levels, higher BMI and diastolic blood pressure. CONCLUSION: This study indicated that insulin was probably a residual risk factor of CHD but not stroke, and that there was a possible presence of obesity paradox in patients with T2DM on statin therapy. In addition to lowering TG and normalizing fasting glucose levels, lower LDL cholesterol level is better for reduction of risk of CHD on statin therapy. On the other hand, lower LDL cholesterol level could potentially be related to higher risk of stroke among populations receiving statin therapy. These findings suggest potential therapeutic targets for residual cardiovascular risk reduction in patients with T2DM on statin therapy.

Prenatal exposure to low-dose di-(2-ethylhexyl) phthalate (DEHP) induces potentially hepatic lipid accumulation and fibrotic changes in rat offspring.

Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer that is widely used to enhance the flexibility and durability of various products. As an endocrine disruptor, DEHP can interfere with normal hormonal functions, posing substantial health risks to organisms. Given the critical role of the liver in DEHP metabolism, we investigated potential liver damage in offspring induced by prenatal exposure to low doses of DEHP in Sprague Dawley rats. Pregnant rats were divided into three groups and administered 20 or 200 µg/kg/day of DEHP or corn oil vehicle control via oral gavage from gestation days 0-20. Male rat offspring were euthanized on postnatal day 84, and blood and liver specimens were collected for analysis. We observed fibrotic changes in the livers of the exposed groups, accompanied by the proliferation and activation of hepatic stellate cells and upregulated expression of TGF-B and collagen 1A1. Additionally, an inflammatory response, characterized by increased macrophage infiltration and elevated levels of pro-inflammatory cytokines, was evident. Third, hepatic and serum triglyceride and serum cholesterol were notably increased, along with upregulated expression of lipid metabolism-related proteins, such as sterol regulatory element-binding protein-1c, acetyl-CoA carboxylase, fatty acid synthase, and diacylglycerol O-acyltransferase 1, particularly in the low-dose group. These results suggest that prenatal exposure to DEHP can disrupt lipid metabolism, resulting in hepatic lipid accumulation in the offspring. This exposure may also induce an inflammatory response that contributes to the development of liver fibrosis. Thus, even at relatively low doses, such exposure can precipitate latent liver damage in offspring.

Incidence and co-infection with COVID-19 of dengue during the COVID-19 pandemic.

The co-infection of dengue and COVID-19 has been regarded as a public health issue for dengue-endemic countries during the COVID-19 pandemic. Travel restrictions might decrease the chance of mosquitoes biting and, thus, reduce the risk of dengue transmission. However, the spread of dengue was reported to increase with the policies of lockdowns and social distancing in specific areas due to delayed interventions in dengue transmission. Of cases experiencing dengue and COVID-19 co-infection, most recovered after receiving supportive care and/or steroid therapy. However, some episodes of severe or fatal diseases in specific individuals, such as pregnant women, have been reported, and the clinical course of this co-infection is unrecognized or unpredictable. Accordingly, it is crucial to promptly identify predictors of developing severe viral diseases among co-infection patients.

Advanced maternal age-related clustering of metabolic abnormalities is associated with risks of adverse pregnancy outcomes.

AIMS: Advanced maternal age (AMA) is correlated with higher risk of adverse pregnancy outcomes while the pathophysiology remains unclear. Our study aimed to investigate whether AMA is linked to the clustering of metabolic abnormalities, which in turn is associated with an increased risk of adverse pregnancy outcomes. METHOD: A total of 857 pregnant woman were recruited in a prospective cohort at National Taiwan University Hospital, from November 2013 to April 2018. Metabolic abnormalities during pregnancy were defined as following: fasting plasma glucose ≥92 mg/dl, body mass index (BMI) ≥24 kg/m2, plasma high-density lipoprotein cholesterol <50 mg/dl, hyper-triglyceridemia (≥140 mg/dl in the first trimester or ≥220 mg/dl in the second trimester), and blood pressure ≥130/85 mmHg. RESULT: Incidence of large for gestational age (LGA), primary caesarean section (CS), and the presence of any adverse pregnancy outcome increased with age. The advanced-age group tended to have more metabolic abnormalities in both the first and the second trimesters. There was a significant association between the number of metabolic abnormalities in the first and the second trimesters and the incidence of LGA, gestational hypertension or preeclampsia, primary CS, preterm birth, and the presence of any adverse pregnancy outcome, adjusted for maternal age. CONCLUSION: AMA is associated with clustering of metabolic abnormalities during pregnancy, and clustering of metabolic abnormalities is correlated with increased risk of adverse pregnancy outcomes.

A Machine-Learning Strategy to Detect Mura Defects in a Low-Contrast Image by Piecewise Gamma Correction.

A detection and classification machine-learning model to inspect Thin Film Transistor Liquid Crystal Display (TFT-LCD) Mura is proposed in this study. To improve the capability of the machine-learning model to inspect panels' low-contrast grayscale images, piecewise gamma correction and a Selective Search algorithm are applied to detect and optimize the feature regions based on the Semiconductor Equipment and Materials International Mura (SEMU) specifications. In this process, matching the segment proportions to gamma values of piecewise gamma is a task that involves derivative-free optimization which is trained by adaptive particle swarm optimization. The detection accuracy rate (DAR) is approximately 93.75%. An enhanced convolutional neural network model is then applied to classify the Mura type through using the Taguchi experimental design method that identifies the optimal combination of the convolution kernel and the maximum pooling kernel sizes. A remarkable defect classification accuracy rate (CAR) of approximately 96.67% is ultimately achieved. The entire defect detection and classification process can be completed in about 3 milliseconds.

The Prognostic Value of D-Dimer in Patients with Acute Myocardial Infarction: A Retrospective Longitudinal Cohort Study in Taiwan.

Background: Serum D-dimer level has been associated with worsening outcomes in patients with acute myocardial infarction. This study aimed to explore the association between serum D-dimer level and clinical outcomes in Taiwanese patients with acute myocardial infarction. Methods: We analyzed Tri-Service General Hospital-Coronary Heart Disease registry data related to patients with acute myocardial infarction who were admitted between January 2014 and December 2018. A total of 748 patients were enrolled and categorized into high (≥ 495 ng/ml) and low (< 495 ng/ml) D-dimer groups. The primary endpoint was in-hospital mortality, and secondary endpoints were post-discharge mortality and post-discharge major adverse cardiovascular events. Results: Overall, 139 patients died, with 77 from cardiovascular causes and 62 from non-cardiovascular causes. In-hospital mortality was higher in the high D-dimer group than in the low D-dimer group. Among the patients alive at discharge, those with a high D-dimer level had higher cardiovascular mortality and future major adverse cardiovascular events than those with a low D-dimer level. Multivariate Cox regression analysis revealed that higher serum D-dimer levels were significantly associated with higher risks of in-hospital mortality [hazard ratio (HR) = 1.11; 95% confidence interval (CI), 1.06-1.16, p < 0.001], subsequent cardiovascular mortality after discharge (HR = 1.15; 95% CI, 1.08-1.22, p < 0.001), and major adverse cardiovascular events (HR = 1.10; 95% CI, 1.04-1.16, p < 0.001). Conclusions: This is the first study in Taiwan to demonstrate that a higher baseline serum D-dimer level was independently associated with higher risks of in-hospital mortality, post-discharge mortality, and major adverse cardiovascular events in patients with acute myocardial infarction.

Prevalence of antibiotic prescribing in COVID-19 patients in China and other low- and middle-income countries during the pandemic (December 2019-March 2021): a systematic review and meta-analysis.

OBJECTIVES: Low- and middle-income countries (LMICs) are particularly vulnerable to the threat of antimicrobial resistance (AMR). Use of antibiotics to treat COVID-19 patients during the pandemic may have contributed to increasing the AMR burden, but systematic evidence is lacking. METHODS: We searched Web of Science, EMBASE, PubMed, China National Knowledge Infrastructure (CNKI) and VIP databases from 1 December 2019 to 31 March 2021. Interventional and observation studies across all settings that reported antibiotic use in at least 10 COVID-19 patients were included. We restricted publications to English and Chinese languages. Screening and data extraction were undertaken by at least two independent reviewers. Results were synthesized using random-effects meta-analyses. Subgroup analyses and meta-regression were used to explore heterogeneities. This review was registered with PROSPERO (CRD42021288291). RESULTS: We included 284 studies involving 210 611 participants in 19 countries. The antibiotic prescribing rates (APRs) in COVID-19 inpatients were 71.7% (95% CI 66.7%-76.5%) in China and 86.5% (77.1%-93.9%) in other LMICs, respectively. APR was lower in mild/moderate cases in China [66.9% (57.9%-75.4%) compared with 91.8% (71.4%-100%) in other LMICs]. High APRs were found among pregnant women and the elderly in China. Disparities in APRs of other patient groups were identified. In studies reporting bacterial infections, the prevalence was 17.3% (10.0%-25.9%) in China and 24.9% (0.1%-68.8%) in other LMICs. Several antibiotics on the WHO 'Watch' and 'Reserve' lists were prescribed frequently in LMICs. CONCLUSIONS: Inappropriate antibiotic use and high prevalence of antibiotic prescribing were found in COVID-19 inpatients in many LMICs.

Bacterial community analysis identifies Klebsiella pneumoniae as a native symbiotic bacterium in the newborn Protobothrops mucrosquamatus.

BACKGROUND: The study of the native microbiome of organisms is crucial. The connection between the native microbiome and the host affects the formation of the innate immune system and the organism's growth. However, the native microbiome of newborn venomous snakes has not been reported. Therefore, we aimed to determine the oral and skin microbiomes of newborn Protobothrops mucrosquamatus. RESULTS: We performed 16 S full-length sequencing on 14 samples collected from 7 newborn P. mucrosquamatus individuals, specifically targeting their oral and skin microbiomes. In terms of the oral and skin microbiome, the main species were Klebsiella pneumoniae lineages. According to subspecies/species analysis, the proportion from highest to lowest was K. quasipneumoniae subsp. similipneumoniae, K. pneumoniae subsp. pneumoniae, and K. pneumoniae subsp. rhinoscleromatis. These three bacteria accounted for 62.5% and 85% of the skin and oral activity, respectively. The oral microbiome of newborn P. mucrosquamatus did not comprise common bacteria found in snakebite wounds or oral cultures in adult snakes. Therefore, the source of other microbiomes in the oral cavities of adult snakes may be the environment or prey. Functional Annotation of the Prokaryotic Taxa analysis showed that the skin/oral native microbiome metabolism was related to fermentation and human infection owing to the dominance of K. pneumoniae lineages. The characteristics of K. pneumoniae may impact the development of venom in venomous snakes. CONCLUSION: The results of the native microbiome in the oral cavity and skin of newborn P. mucrosquamatus demonstrated that the habitat environment and prey capture may affect the composition of bacteria in adult snakes. We hypothesized that the native microbiome influences newborn venomous snakes and that K. pneumoniae lineages related to citrate fermentation may play a role in venom growth. However, further verification of this is required.

Inhibition of monoamine oxidase B reduces atherosclerosis and fatty liver in mice.

Oxidative stress is vital for pathophysiology of atherosclerosis and non-alcoholic fatty liver disease (NAFLD). Monoamine oxidase (MAO) is an important source of oxidative stress in the vascular system and liver. However, the effect of MAO inhibition on atherosclerosis and NAFLD has not been explored. In the present study, MAO A and B expressions were increased in atherosclerotic plaques in human and apolipoprotein E (ApoE)-deficient mice. Inhibition of MAO B (by deprenyl), but not MAO A (by clorgyline), reduced the atheroma area in the thoracic aorta and aortic sinus in ApoE-deficient mice fed the cholesterol-enriched diet for 15 weeks. MAO B inhibition attenuated oxidative stress, expression of adhesion molecules, production of inflammatory cytokines, and macrophage infiltration in atherosclerotic plaques and decreased plasma triglyceride and low-density lipoprotein (LDL) cholesterol concentrations. MAO B inhibition had no therapeutic effect on restenosis in the femoral artery wire-induced injury model in C57BL/6 mice. In the NAFLD mouse model, MAO B inhibition reduced lipid droplet deposition in the liver and hepatic total cholesterol and triglyceride levels in C57BL/6 mice fed high-fat diets for 10 weeks. Key enzymes for triglyceride and cholesterol biosynthesis (fatty acid synthase and 3-hydroxy-3-methylglutaryl-CoA reductase, HMGCR) and inflammatory markers were inhibited, and cholesterol clearance was up-regulated (increased LDL receptor expression and reduced proprotein convertase subtilisin/kexin type 9, PCSK9, expression) by MAO B inhibition in the liver. These results were also demonstrated in the HepG2 liver cell model. Our data suggest that MAO B inhibition is a potential and novel treatment for atherosclerosis and NAFLD.

Risk of placenta accreta spectrum following myomectomy: a nationwide cohort study.

BACKGROUND: Whether myomectomy increases the risk of placenta accreta spectrum in the following pregnancies remains controversial. OBJECTIVE: This study aimed to investigate the effect of myomectomy on the risk of placenta accreta spectrum in the following pregnancies. Moreover, different methods of myomectomy on the risk of placenta accreta spectrum were explored. STUDY DESIGN: A nationwide cohort study was conducted using data from the Taiwan National Health Insurance Research Database, including all pregnant patients in Taiwan who gave birth between January 2008 and December 2017. A 1:1 propensity score estimation matching was performed for the analysis of myomectomy on the risk of placenta accreta spectrum. Among pregnant patients who received myomectomy, different methods of myomectomy on the risk of placenta accreta spectrum were compared with the control group. RESULTS: Among the 1,371,458 pregnant patients in this study, 11,255 pregnant patients had a history of myomectomy. The risk of placenta accreta spectrum was higher in pregnant patients with a history of myomectomy than in pregnant patients without a history of myomectomy (incidence: 0.96% vs 0.20%; adjusted odds ratio, 2.28; 95% confidence interval, 1.85-2.81; P<.01). Among pregnant patients with a history of myomectomy, 5045 (46.87%) received laparotomic myomectomy, 3973 (36.93%) received laparoscopic myomectomy, and 1742 (16.20%) received hysteroscopic myomectomy. The incidence of placenta accreta spectrum was higher in the hysteroscopic group than in the laparotomic group or the laparoscopic group (1.89% [hysteroscopic group] vs 0.71% [laparotomic group] and 0.81% [laparoscopic group]; P<.05). Compared with patients without a history of myomectomy, the adjusted odds ratio for placenta accreta spectrum was 3.88 (95% confidence interval, 2.68-5.63; P<.05) in the hysteroscopic group. CONCLUSION: Myomectomy, especially hysteroscopic myomectomy, is associated with an increased risk of placenta accreta spectrum in the subsequent pregnancy.

Enhancing optical characteristics of mediator-assisted wafer-scale MoS2and WS2on h-BN.

Two-dimensional (2D) materials and their heterostructures exhibit intriguing optoelectronic properties; thus, they are good platforms for exploring fundamental research and further facilitating real device applications. The key is to preserve the high quality and intrinsic properties of 2D materials and their heterojunction interface even in production scale during the transfer and assembly process so as to apply in semiconductor manufacturing field. In this study, we successfully adopted a wet transfer existing method to separate mediator-assisted wafer-scale from SiO2/Si growing wafer for the first time with intermediate annealing to fabricate wafer-scale MoS2/h-BN and WS2/h-BN heterostructures on a SiO2/Si wafer. Interestingly, the high-quality wafer-scale 2D material heterostructure optical properties were enhanced and confirmed by Raman and photoluminescence spectroscopy. Our approach can be applied to other 2D materials and expedite mass production for industrial applications.

Predictive models for short-term mortality and length of hospital stay among adults with community-onset bacteraemia before and during the COVID-19 pandemic: application of early data dynamics.

BACKGROUND: The development of scoring systems to predict the short-term mortality and the length of hospital stay (LOS) in patients with bacteraemia is essential to improve the quality of care and reduce the occupancy variance in the hospital bed. METHODS: Adults hospitalised with community-onset bacteraemia in the coronavirus disease 2019 (COVID-19) and pre-COVID-19 eras were captured as the validation and derivation cohorts in the multicentre study, respectively. Model I incorporated all variables available on day 0, Model II incorporated all variables available on day 3, and Models III, IV, and V incorporated the variables that changed from day 0 to day 3. This study adopted the statistical and machine learning (ML) methods to jointly determine the prediction performance of these models in two study cohorts. RESULTS: A total of 3,639 (81.4%) and 834 (18.6%) patients were included in the derivation and validation cohorts, respectively. Model IV achieved the best performance in predicting 30-day mortality in both cohorts. The most frequently identified variables incorporated into Model IV were deteriorated consciousness from day 0 to day 3 and deteriorated respiration from day 0 to day 3. Model V achieved the best performance in predicting LOS in both cohorts. The most frequently identified variables in Model V were deteriorated consciousness from day 0 to day 3, a body temperature ≤ 36.0 °C or ≥ 39.0 °C on day 3, and a diagnosis of complicated bacteraemia. CONCLUSIONS: For hospitalised adults with community-onset bacteraemia, clinical variables that dynamically changed from day 0 to day 3 were crucial in predicting the short-term mortality and LOS.

Lack of Evidence for Ribavirin Treatment of Lassa Fever in Systematic Review of Published and Unpublished Studies1.

Ribavirin has been used widely to treat Lassa fever in West Africa since the 1980s. However, few studies have systematically appraised the evidence for its use. We conducted a systematic review of published and unpublished literature retrieved from electronic databases and gray literature from inception to March 8, 2022. We identified 13 studies of the comparative effectiveness of ribavirin versus no ribavirin treatment on mortality outcomes, including unpublished data from a study in Sierra Leone provided through a US Freedom of Information Act request. Although ribavirin was associated with decreased mortality rates, results of these studies were at critical or serious risk for bias when appraised using the ROBINS-I tool. Important risks for bias related to lack of control for confounders, immortal time bias, and missing outcome data. Robust evidence supporting the use of ribavirin in Lassa fever is lacking. Well-conducted clinical trials to elucidate the effectiveness of ribavirin for Lassa fever are needed.

Systematic review and narrative synthesis of surveillance practices after endovascular intervention for lower limb peripheral arterial disease.

OBJECTIVE: The optimal timing and modality of surveillance after endovascular intervention for peripheral arterial disease is controversial, and no randomized trial to assess the value of peripheral endovascular intervention has ever been performed. The aim of this systematic review was to examine the practice of surveillance after peripheral endovascular intervention in randomized trials. METHODS: We used the Medline, Embase, Cochrane Library, and WHO trial registry databases in this systematic review of the literature to capture surveillance strategies used in randomized trials comparing endovascular interventions. Surveillance protocols were assessed for completeness, modalities used, duration, and intensity. RESULTS: Ninety-six different surveillance protocols were reported in 103 trials comparing endovascular interventions. Protocol specification was incomplete in 32% of trials. The majority of trials used multiple surveillance modalities (mean of 3.46 modalities), most commonly clinical examination (96%), ankle-brachial index (80%), duplex ultrasound examination (75%), and digital subtraction angiography (51%). Trials involving infrapopliteal lesions used more angiographic surveillance than trials with femoropopliteal lesions (P = .006). The median number of surveillance visits in the first 12 months after intervention was three and the mean surveillance duration was 21 months. Trials treating infrapopliteal vessels had a higher surveillance intensity compared with those treating femoropopliteal lesions in the first 12 months after endovascular intervention (mean 5 vs 3 surveillance visits; P = .017). Trials with drug-eluting devices had longer surveillance duration compared with those without (mean 26 vs 19 months; P = .020). CONCLUSIONS: There is a high level of variation in the modality, duration, and intensity of surveillance protocols used in randomized trials comparing different types of peripheral endovascular arterial intervention. Further research is required to determine the value and impact of postprocedural surveillance on patient outcomes.

Decreased nutrient digestibility due to viscosity is independent of the amount of dietary fibre fed to growing pigs.

Fibre content and its effect on chyme viscosity are associated with changes in the digestive system of humans and pigs. It is unclear if fibre content and viscosity affect digestive function independently or interactively. We evaluated apparent ileal digestibility (AID) of nutrients and intestinal function in thirty-six ileal-cannulated barrows fed for 29 d either maize-soyabean meal (MSBM) or high-fibre MSBM + 30 % distillers dried grains with solubles (MSBM + DDGS) modified to three levels of viscosity by adding 5 % non-viscous cellulose (CEL), 6·5 % medium-viscous carboxymethylcellulose (MCMC) or 6·5 % high-viscous CMC (HCMC). Digesta were collected on days 27 and 28 and intestinal samples on day 29. Feeding CMC, regardless of fibre content, increased viscosity of whole digesta (P = 0·003) and digesta supernatant (P < 0·0001) compared with CEL. Feeding MSBM + DDGS or CMC decreased AID of DM (P = 0·003; P < 0·0001) and crude protein (P = 0·02; P < 0·0001) compared with MSBM or CEL. Feeding CMC regardless of fibre content increased jejunal crypt depth (P = 0·02) and ileal goblet cell area (P = 0·004) compared with CEL. Adding DDGS or CMC did not affect villus height and gene expression of jejunal monosaccharide and amino acid transporters. Feeding HCMC, regardless of fibre content, elevated amylase activity by 46 and 50 % in jejunal (P = 0·03) and ileal digesta (P = 0·01) compared with CEL. In summary, diets with increased viscosity decreased nutrient digestibility and induced intestinal changes that were independent of the amount of fibre fed.

Comprehensive assessment of bacterial communities and their functional profiles in the Huang Gang Creek in the Tatun Volcano Group basin, Taiwan using 16S rRNA amplicon sequencing.

The microbial characteristics of water bodies located in the outflow of hot springs may affect the water quality parameters of the associated river ecosystem. Using 16S rRNA amplicon sequencing, we investigated the bacterial diversity and functional profiles of the Huang Gang (HG) Creek, located in the trace metal-rich, acid-sulfate thermal springs zone of the Tatun Volcano Group (TVG). Biofilms and water samples were collected from the upstream, midstream, and geothermal valleys and downstream of the creek. The results showed that the biofilm and water samples had distinct bacterial diversity and abundance profiles. Acidophilic sulfur-oxidizing bacteria were found to be more abundant in water samples, whereas aquatic photosynthetic bacterial communities were dominant in biofilms. The water samples were contaminated with Legionella and Chlamydiae, which could contaminate the nearby river and cause clinical infections in humans. The upstream samples were highly unique and displayed higher diversity than the other sites. Moderate thermo-acidophiles were dominant in the upstream and midstream regions, whereas the geothermal valley and downstream samples were abundant in thermo-acidophiles. In addition, functional profiling revealed higher expression of sulfur, arsenic, and iron-related functions in water and lead-related functions in the biofilms of the creek. As described in previous studies, the hydrochemical properties of the HG Creek were influenced by the TVG hot springs. Our findings indicated that the hydrochemical properties of the HG Creek were highly correlated with the bacterial diversity and functional potential of running water as compared to biofilms.

Comparison of cumulative dispersed energy between conventional phacoemulsification and femtosecond laser-assisted cataract surgery with two different lens fragmentation patterns.

The purpose of the study is to compare the total ultrasound power used between eyes undergoing different lens fragmentation patterns of femtosecond laser-assisted cataract surgery (FLACS) and conventional phacoemulsification surgery (CPS). A total of 506 patient eyes underwent preoperative grading of lens opacity using the Lens Opacity Classification System III (LOCSIII). The eyes were divided into two subgroups: subgroup 1 had a LOCSIII grade of 1-3, and subgroup 2 had a LOCSIII grade of 4-6. The eyes underwent FLACS (LenSx) for clear corneal wound, capsulotomy, and lens fragmentation. Either a grid pattern or radial pattern was used for lens fragmentation. The eyes received one of the following three treatments: (1) CPS without femtosecond laser assistant, (2) FLACS with a grid pattern (FGP) lens fragment, or (3) FLACS with a quadrant pattern (FQP) lens fragment. The mean cumulative dispersed energy (CDE) for each subgroup and treatment was evaluated. The mean CDE was lower in the two FLACS groups (1.21±1.91 in FGP and 1.22±1.92 in FQP) than that in the CPG group (2.67±2.84). In subgroup 1, CDE was higher in the CPG group (1.54±1.18) as compared with the FLACS groups (0.16±0.31 in FGP and 0.74±1.17 in FQP; P<0.001). In subgroup 2, CDE was higher in the CPG (6.47±3.46) as compared with the FLACS groups (2.74±2.21 in FGP and 5.34±2.17 in FQP; P<0.001). CDE was lower in the two FLACS groups than that in the CPS group, and CDE was the lowest with FGP in both subgroups 1 and 2.