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The observation of Arctic sea ice is of great significance to monitoring of the polar environment, research on global climate change and application of Arctic navigation. Compared to optical imagery and SAR imagery, passive microwave images can be obtained for all-sky conditions with high time resolution. However, the spatial resolution of passive microwave images is relatively low (6.25 km – 25 km) for the observation of detailed sea ice characteristics and small-scale sea ice geographical phenomena. Therefore, in this paper, considering the suitability of different alignment and fusion strategies to the characteristics of passive microwave images of sea ice, two multi-images deep learning super-resolution (SR) algorithms, Recurrent Back-Projection Network (RBPN) and network of Temporal Group Attention (TGA), are selected to test the effects of SR technique for passive microwave images of sea ice. Both qualitative and quantitative comparisons are provided for the SR results oriented from two algorithms. Overall, the SR performance of TGA algorithm outperforms RBPN algorithm for the passive microwave images of sea ice.

LILRA3 is related to IBD and was markedly increased in IBD patients compared with healthy controls. LILRA3 functions as an anti‐inflammatory modulator by down‐regulating IFN‐γ, TNF‐α and up‐regulating IL‐10 secretion in monocytes. LILRA3 might promote monocyte proliferation through Akt and MEK/Erk signaling pathways., Summary Growing evidence shows that a homozygous 6·7‐kb deletion of the novel anti‐inflammatory molecule leukocyte immunoglobulin‐like receptor A3 (LILRA3) is associated with many autoimmune disorders. However, its effects on pathogenesis of inflammatory bowel disease (IBD) have yet not been clarified. LILRA3 is mainly expressed in monocytes, whereas its effects on biological behaviors of monocytes have not been systematically reported. In our study, to investigate the association between LILRA3 polymorphism and IBD susceptibility, LILRA3 polymorphism was assessed in 378 IBD patients and 509 healthy controls. Quantitative real time PCR (qRT–PCR), Western blot and immunohistochemistry (IHC) were employed to detect the LILRA3 expression in IBD patient blood and intestinal samples. The human U937 monocyte cell line was employed to establish LILRA3 over‐expressing cells and the effects of LILRA3 on the biological behaviors of U937 cells were systematically explored. Although no association of the polymorphism with IBD development was found, LILRA3 expression was markedly increased in IBD patients compared with healthy controls. Over‐expression of LILRA3 in monocytes led to significant decreases in secretion of interferon (IFN)‐γ, tumor necrosis factor (TNF)‐α and interleukin (IL)‐6. Additionally, LILRA3 abated monocyte migration by reducing the expression of several chemokines and enhanced monocyte phagocytosis by increasing CD36 expression. Furthermore, LILRA3 promoted monocyte proliferation through a combination of Akt and extracellular receptor kinase/mitogen‐activated protein kinase (Erk/MEK) signaling pathways. We report for the first time, to our knowledge, that LILRA3 is related to IBD and functions as an anti‐inflammatory modulator in U937 cells.

Summary We report findings from a new survey of US public attitudes toward human-animal chimeric embryo (HACE) research, designed to compare with recently reported Japanese survey data. We find that 59% of the US public can personally accept the process of injecting human induced pluripotent stem cells into genetically modified swine embryos and having human tissues produced in a pig's body transplanted into a human. This is greater acceptance than in Japan, and there is even strong acceptance among those with strong religious affiliations and who self-identify as conservatives. We argue that strong public support for HACE research, as well as the emerging literature suggesting that humanization of research animals is very unlikely, should compel the NIH to lift its current moratorium on HACE research., Highlights • 430 US participants in a national survey on human-animal chimeric embryo research • 83% of respondents can personally accept research on human-animal chimeric embryos • Self-identified political conservatives accept human-animal chimera research • Individuals opposed to animal research also accept human-animal chimera research, In this report, Crane and colleagues report findings on US public attitudes toward human-animal chimeric embryo research. A majority of survey respondents personally accept the process of injecting human stem cells into genetically modified swine embryos and transplanting human tissues produced in a pig's body. Strong public support should compel the NIH to lift the moratorium on human-animal chimeric embryo research.

Although elevated plasma interleukin-8 (pIL-8) has been associated with poor outcome to immune checkpoint blockade 1, this has not been comprehensively evaluated in large randomized studies. Here we analyzed circulating pIL-8 and IL8 gene expression in peripheral blood mononuclear cells and tumors of patients treated with atezolizumab (anti-PD-L1 monoclonal antibody) from multiple randomized trials representing 1,445 patients with metastatic urothelial carcinoma (mUC) and metastatic renal cell carcinoma. High levels of IL-8 in plasma, peripheral blood mononuclear cells and tumors were associated with decreased efficacy of atezolizumab in patients with mUC and metastatic renal cell carcinoma, even in tumors that were classically CD8+ T cell inflamed. Low baseline pIL-8 in patients with mUC was associated with increased response to atezolizumab and chemotherapy. Patients with mUC who experienced on-treatment decreases in pIL-8 exhibited improved overall survival when treated with atezolizumab but not with chemotherapy. Single-cell RNA sequencing of the immune compartment showed that IL8 is primarily expressed in circulating and intratumoral myeloid cells and that high IL8 expression is associated with downregulation of the antigen-presentation machinery. Therapies that can reverse the impacts of IL-8-mediated myeloid inflammation will be essential for improving outcomes of patients treated with immune checkpoint inhibitors.

Purpose: This study aimed to evaluate the effects of irisin on bones of ovariectomized (OVX) mice, to explore a possible treatment for postmenopausal osteoporosis.Methods: The OVX mice were treated...

Objective To evaluate the use of Ilizarov external mini-fixation in the treatment of Monteggia fractures (dislocation of the radial head with an associated fracture of the proximal ulna) in children. Methods Children with proximal ulnar fracture were included and underwent fracture reduction surgery with Ilizarov external mini-fixators, followed by immobilization of the supinated forearm with plaster. The reduction was evaluated intra-operatively using arthrography. Mackay criteria were used to evaluate clinical outcomes at follow-up. Results A total of 15 children were included in the study. Mackay efficacy was 100 %, indicating excellent outcomes using the Ilizarov external mini-fixator. Conclusion Use of the Ilizarov external mini–fixator is particularly suitable in the treatment of children with comminuted and compression fractures of proximal ulna. It is easy to operate, low invasive and is worthy of promotion.

High-aspect-ratio and hierarchically nanostructured surfaces are common in nature. Synthetic variants are of interest for their specific chemical, mechanic, electric, photonic, or biologic properties but are cumbersome in fabrication or suffer from structural collapse. Here, we replicated and directly biofunctionalized robust, large-area, and high-aspect-ratio nanostructures by nanoimprint lithography of an off-stoichiometric thiol-ene-epoxy polymer. We structured-in a single-step process-dense arrays of pillars with a diameter as low as 100 nm and an aspect ratio of 7.2; holes with a diameter of 70 nm and an aspect ratio of20; and complex hierarchically layered structures, all with minimal collapse and defectivity. We show that the nanopillar arrays alter mechanosensing of human hepatic cells and provide precise spatial control of cell attachment. We speculate that our results can enable the widespread use of high-aspect-ratio nanotopograhy applications in mechanics, optics, and biomedicine.

Objectives The Ice Hockey Summit III provided updated scientific evidence on concussions in hockey to inform these 5 objectives: (1) describe sport related concussion (SRC) epidemiology; (2) classify prevention strategies; (3) define objective, diagnostic tests; (4) identify treatment; and (5) integrate science and clinical care into prioritized action plans and policy. Methods Our action plan evolved from 40 scientific presentations. The 155 attendees (physicians, athletic trainers, physical therapists, nurses, neuropsychologists, scientists, engineers, coaches, and officials) voted to prioritize these action items in the final Summit session. Results To (1) establish a national and international hockey database for SRCs at all levels; (2) eliminate body checking in Bantam youth hockey games; (3) expand a behavior modification program (Fair Play) to all youth hockey levels; (4) enforce game ejection penalties for fighting in Junior A and professional hockey leagues; (5) establish objective tests to diagnose concussion at point of care; and (6) mandate baseline testing to improve concussion diagnosis for all age groups. Conclusions Expedient implementation of the Summit III prioritized action items is necessary to reduce the risk, severity, and consequences of concussion in the sport of ice hockey.

Background Delays in Crohn's disease (CD) diagnosis are positively associated with ileal location and an increased risk of complications. Aim To develop a simple risk assessment tool to enable primary care physicians to recognise potential ileal CD earlier, shortening the delay to specialist investigation METHODS: Three cohorts were acquired for this study. Cohort 1 included 61 patients retrospectively identified with ileal CD between 2000 and 2010 and 78 matched controls drawn from a cohort referred for investigation of abdominal symptoms. Cohort 2 included 42 individuals diagnosed with ileal CD and 57 controls identified prospectively. Cohort 3 included an additional 84 individuals with ileal CD and 495 without CD referred for colonoscopy. Clinical symptoms and serological biomarkers were acquired and used to develop a risk prediction algorithm. The algorithm was trained independently on each of the three cohorts and tested on the latter two cohorts. Results Altered bowel habit with abdominal pain combined with derangements in white cell count (WCC), albumin and platelet counts were important features in predicting ileal CD (AUC = 0.92, 95% CI = 0.89-0.92). This was validated in cohorts 2 (AUC = 0.96, 95% CI = 0.95-0.98) and 3 (AUC = 0.94, 95% CI = 0.92-0.96). C-reactive protein was independently associated with ileal CD but non-signficant in a multivariate model. Conclusion A web-based risk stratification tool for ileal CD has been developed from objective and symptom-based criteria. This tool enables primary care physicians to more confidently request urgent specialist assessment for patients identified as at high risk for ileal CD.

Vertical transmission from mother-to-child is an important mode of hepatitis B virus (HBV) infection, accounting for up to half of all incident cases globally. We evaluated the uptake of HBV neonatal vaccination and immunoglobulin delivery in Queensland, Australia, between 2001 and 2013. We identified HBV-positive mothers using linked notifiable conditions, hospitalisation, and perinatal administrative data. Perinatal receipt of monovalent HBV vaccine and hepatitis B immunoglobulin were examined. Of 710,859 live births, with 5753 infants (0.81%) born to identified HBV-positive mothers; 91.7% received HBV neonatal vaccine. Immunoglobulin uptake was 20.0% in 2012 and 36.6% in 2013. Uptake was higher when the mother's HBV-positive status was recorded in perinatal records (69.6% if maternal HBV status recorded on perinatal data collection vs 9.5% otherwise). Delivery of neonatal HBV vaccination in Queensland was high. Improved identification and documentation of HBV-positive mothers' status during the antenatal period was associated with increased immunoglobulin administration.

Background Hepatic ischemia/reperfusion-induced pancreatic injury (HI/RPI) is an important pathophysiological phenomenon in clinics. Exenatide is found to have hepatopancreatic protection; however, the half-life of exenatide is extremely short, which limits its clinical application. In the present study, we described an exenatide nanocarrier based on poly(L-lysine)-poly(ethylene glycol)-poly(L-lysine) (PLL-PEG-PLL) and aimed to investigate the protective effects of exenatide/PLL-PEG-PLL on HI/RPI. Methods PLL-PEG-PLL was synthesized and estimated by being applied as a nanocarrier for lengthening delivery of exenatide. Exenatide was loaded into PLL-PEG-PLL by electrostatic interactions at pH 7.4. The loading and release of exenatide from PLL-PEG-PLL were characterized in vitro. The pancreatic protection of exenatide/PLL-PEG-PLL was assessed using the animal model, histopathological examination, blood biochemical indices detection, antioxidant activity, and anti-inflammatory evaluation in vivo. Results Exenatide/PLL-PEG-PLL displayed efficient loading and sustained release. Exenatide/PLL-PEG-PLL complex moderated HI/RPI and enlarged islet functionality compared to free exenatide. Conclusion We propose that the nanocarrier PLL-PEG-PLL may function as a potent exenatide nanocarrier for augmenting anti-HI/RPI pharmacotherapy with unprecedented clinical benefits.

Administration of freeze-dried powder of Saskatoon berry (SB), a popular fruit enriched with antioxidants, reduced glucose level, inflammatory markers and gut microbiota disorder in high fat-high sucrose (HFHS) diet-induced insulin resistant mice. The present study examined the dose-response relationship in metabolic, inflammatory and gut microbiotic variables to SB power (SBp) supplementation in HFHS diet-fed mice. Male C57 BL/6J mice were fed with HFHS diet supplemented with 0, 1%, 2.5% or 5% SBp for 11 weeks. HFHS diet significantly increased the levels of fast plasma glucose (FPG), cholesterol, triglycerides, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), tumor necrosis factor-α, monocyte chemotactic protein-1 and plasminogen activator inhibitor-1, but decreased fecal Bacteroidetes phylum bacteria and Muribaculaceae family bacteria compared to low fat diet. SBp dose-dependently reduced metabolic and inflammatory variables and gut dysbiosis in mice compared with mice receiving HFHS diet alone. Significant attenuation of HFHS diet-induced biochemical disorders were detected in mice receiving ≥1% SBp. The abundances of Muribaculaceae family bacteria negatively correlated with body weights, FPG, lipids, insulin, HOMA-IR and inflammatory markers in the mice. The results suggest that SBp supplementation dose-dependently attenuated HFHS diet-induced metabolic and inflammatory disorders, which was associated with the amelioration of gut dysbiosis in the mice.

Treatment of the cytokine release syndrome (CRS) has become an important part of rescuing hospitalized COVID-19 patients. Here, we systematically explored the transcriptional regulators of inflammatory cytokines involved in the COVID-19 CRS to identify candidate transcription factors (TFs) for therapeutic targeting using approved drugs. We integrated a resource of TF-cytokine gene interactions with single-cell RNA-seq expression data from bronchoalveolar lavage fluid cells of COVID-19 patients. We found 581 significantly correlated interactions, between 95 TFs and 16 cytokines upregulated in the COVID-19 patients, that may contribute to pathogenesis of the disease. Among these, we identified 19 TFs that are targets of FDA approved drugs. We investigated the potential therapeutic effect of 10 drugs and 25 drugs combinations on inflammatory cytokine production, which revealed two drugs that inhibited cytokine production and numerous combinations that show synergistic efficacy in downregulating cytokine production. Further studies of these candidate repurposable drugs could lead to a therapeutic regimen to treat the CRS in COVID-19 patients.

The GlueX experiment at Jefferson Lab has been designed to study photoproduction reactions with a 9-GeV linearly polarized photon beam. The energy and arrival time of beam photons are tagged using a scintillator hodoscope and a scintillating fiber array. The photon flux is determined using a pair spectrometer, while the linear polarization of the photon beam is determined using a polarimeter based on triplet photoproduction. Charged-particle tracks from interactions in the central target are analyzed in a solenoidal field using a central straw-tube drift chamber and six packages of planar chambers with cathode strips and drift wires. Electromagnetic showers are reconstructed in a cylindrical scintillating fiber calorimeter inside the magnet and a lead-glass array downstream. Charged particle identification is achieved by measuring energy loss in the wire chambers and using the flight time of particles between the target and detectors outside the magnet. The signals from all detectors are recorded with flash ADCs and/or pipeline TDCs into memories allowing trigger decisions with a latency of 3.3 $\mu$s. The detector operates routinely at trigger rates of 40 kHz and data rates of 600 megabytes per second. We describe the photon beam, the GlueX detector components, electronics, data-acquisition and monitoring systems, and the performance of the experiment during the first three years of operation., Comment: Accepted by Nuclear Instruments and Methods A, 78 pages, 54 figures

Background: First Nations (FN) women have a higher risk of diabetes than non-FN women in Canada. Prenatal education and breastfeeding may reduce the risk of diabetes in mothers and offspring. The rates of breastfeeding initiation and participation in the prenatal program are low in FN communities. Methods: A prenatal educational website, social media-assisted prenatal chat groups and community support teams were developed in three rural or remote FN communities in Manitoba. The rates of participation of pregnant women in prenatal programs and breastfeeding initiation were compared before and after the start of the remote prenatal education program within 2014-2017. Findings: The participation rate of FN pregnant women in rural or remote communities in the prenatal program and breastfeeding initiation during 1-year after the start of the community-based remote prenatal education program were significantly increased compared to that during 1-year before the start of the program (54% versus 36% for the participation rate, 50% versus 34% for breastfeeding initiation, p

In this work, an abundance of ice-nucleating particles (INPs) from livestock facilities was studied through laboratory measurements from cloud-simulation chamber experiments and field investigation in the Texas Panhandle. Surface materials from two livestock facilities, one in the Texas Panhandle and another from McGregor, Texas, were selected as dust proxies for laboratory analyses. These two samples possessed different chemical and biological properties. A combination of aerosol interaction and dynamics in the atmosphere (AIDA) measurements and offline ice spectrometry was used to assess the immersion freezing mode ice nucleation ability and efficiency of these proxy samples at temperatures above −29 ∘C. A dynamic filter processing chamber was also used to complement the freezing efficiencies of submicron and supermicron particles collected from the AIDA chamber. For the field survey, periodic ambient particle sampling took place at four commercial livestock facilities from July 2017 to July 2019. INP concentrations of collected particles were measured using an offline freezing test system, and the data were acquired for temperatures between −5 and −25 ∘C. Our AIDA laboratory results showed that the freezing spectra of two livestock dust proxies exhibited higher freezing efficiency than previously studied soil dust samples at temperatures below −25 ∘C. Despite their differences in composition, the freezing efficiencies of both proxy livestock dust samples were comparable to each other. Our dynamic filter processing chamber results showed on average approximately 50 % supermicron size dominance in the INPs of both dust proxies. Thus, our laboratory findings suggest the importance of particle size in immersion freezing for these samples and that the size might be a more important factor for immersion freezing of livestock dust than the composition. From a 3-year field survey, we measured a high concentration of ambient INPs of 1171.6 ± 691.6 L−1 (average ± standard error) at −25 ∘C for aerosol particles collected at the downwind edges of livestock facilities. An obvious seasonal variation in INP concentration, peaking in summer, was observed, with the maximum at the same temperature exceeding 10 000 L−1 on 23 July 2018. The observed high INP concentrations suggest that a livestock facility is a substantial source of INPs. The INP concentration values from our field survey showed a strong correlation with measured particulate matter mass concentration, which supports the importance of size in ice nucleation of particles from livestock facilities.

The dual anticytokine and antiviral actions of baricitinib reduce SARS-CoV-2 infectivity in organoids and morbidity in people., Using AI, we identified baricitinib as having antiviral and anticytokine efficacy. We now show a 71% (95% CI 0.15 to 0.58) mortality benefit in 83 patients with moderate-severe SARS-CoV-2 pneumonia with few drug-induced adverse events, including a large elderly cohort (median age, 81 years). An additional 48 cases with mild-moderate pneumonia recovered uneventfully. Using organotypic 3D cultures of primary human liver cells, we demonstrate that interferon-α2 increases ACE2 expression and SARS-CoV-2 infectivity in parenchymal cells by greater than fivefold. RNA-seq reveals gene response signatures associated with platelet activation, fully inhibited by baricitinib. Using viral load quantifications and superresolution microscopy, we found that baricitinib exerts activity rapidly through the inhibition of host proteins (numb-associated kinases), uniquely among antivirals. This reveals mechanistic actions of a Janus kinase-1/2 inhibitor targeting viral entry, replication, and the cytokine storm and is associated with beneficial outcomes including in severely ill elderly patients, data that incentivize further randomized controlled trials.

The development of commercially available discrete element modeling software packages such as Particle Flow Code combined with the improved computational power of desktop PCs have created opportunities to apply discrete element models to the modeling of oil sand behaviour. Discrete element models can simulate micro-mechanical phenomena and can provide fundamental insight into the physical behaviour of oil sand that cannot be captured in finite element or boundary element models. Particle Flow Code (PFC) is being used to study the geomechanical behaviour of oil sands. This paper presents results from initial research conducted to establish the input parameters for PFC to simulate triaxial tests on reconstituted oil sands.

Treatment of the cytokine release syndrome (CRS) has become an important part of rescuing hospitalized COVID-19 patients. Here, we systematically explored the transcriptional regulators of inflammatory cytokines involved in the COVID-19 CRS to identify candidate transcription factors (TFs) for therapeutic targeting using approved drugs. We integrated a resource of TF-cytokine gene interactions with single-cell RNA-seq expression data from bronchoalveolar lavage fluid cells of COVID-19 patients. We found 581 significantly correlated interactions, between 95 TFs and 16 cytokines upregulated in the COVID-19 patients, that may contribute to pathogenesis of the disease. Among these, we identified 19 TFs that are targets of FDA approved drugs. We investigated the potential therapeutic effect of 10 drugs and 25 drug combinations on inflammatory cytokine production in peripheral blood mononuclear cells, which revealed two drugs that inhibited cytokine production and numerous combinations that show synergistic efficacy in downregulating cytokine production. Further studies of these candidate repurposable drugs could lead to a therapeutic regimen to treat the CRS in COVID-19 patients.

OBJECTIVECurrent guidelines do not specify timing for management of acute spinal cord injury (aSCI) due to lack of high-quality evidence supporting specific intervals for intervention. Randomized prospective trials may be unethical. Nonetheless, physicians have been sued for delays in diagnosis and intervention.METHODSThe authors reviewed both the medical literature supporting the guidelines and the legal cases reported in the Westlaw and Lexis Advance databases from 1972 to 2018 resulting in awards or settlements, to identify whether surgeons are vulnerable to litigation despite the existence of guidelines not mandating specific timing of care.RESULTSTiming of intervention was related to claims in 59 (36%) of 163 cases involving SCI. All 22 trauma cases identified cited timing of intervention, sometimes related to delayed diagnosis, as a reason for the lawsuit. The mean award of 10 cases in which the plaintiffs’ awards were disclosed was $4,294,384. In the majority of cases, award amounts were not disclosed.CONCLUSIONSBecause conduct of a prospective, randomized trial to investigate surgical timing of intervention for aSCI may not be achievable, evidence-based guidelines will be unlikely to mandate specific timing. Nonetheless, surgeons who unreasonably delay intervention for aSCI may be at risk for litigation due to treatment delay. This is increasingly likely in an environment where “complete” SCI is difficult to verify. SCI may at some point be recognized as a surgical emergency, as brain injury generally is, despite a lack of prospective randomized trials supporting this implementation, challenging the feasibility of the US trauma infrastructure to provide care for these patients.

BACKGROUND: It is unclear whether intrauterine exposure to maternal diabetes is associated with risk factors for cardiovascular disease and related end points in adulthood. We examined this potential association in a population-based birth cohort followed up to age 35 years. METHODS: We performed a cohort study of offspring born between 1979 and 2005 (n = 293 546) and followed until March 2015 in Manitoba, Canada, using registry-based administrative data. The primary exposures were intrauterine exposure to gestational diabetes and type 2 diabetes mellitus. The primary outcome was a composite measure of incident cardiovascular disease events, and the secondary outcome was a composite of risk factors for cardiovascular disease in offspring followed up to age 35 years. RESULTS: The cohort provided 3 628 576 person-years of data (mean age at latest follow-up 20.5 [standard deviation 6.4] years, 49.3% female); 2765 (0.9%) of the offspring experienced a cardiovascular disease end point, and 12 673 (4.3%) experienced a cardiovascular disease risk factor. After propensity score matching, the hazard for cardiovascular disease end points was elevated in offspring exposed to gestational diabetes (adjusted hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.12–1.79) but not type 2 diabetes (adjusted HR 1.40, 95% CI 0.98–2.01). A similar association was observed for cardiovascular disease risk factors (gestational diabetes: adjusted HR 1.92, 95% CI 1.75–2.11; type 2 diabetes: adjusted HR 3.40, 95% CI 3.00–3.85). INTERPRETATION: Intrauterine exposure to maternal diabetes was associated with higher morbidity and risk related to cardiovascular disease among offspring up to 35 years of age.

Setting Shanghai is a mega city where 39% of the population comprises internal migrants. Objective To examine the different roles played by migrants and permanent residents in the transmission of multidrug-resistant tuberculosis (MDR-TB). Design We conducted a population-based cohort study to assess MDR-TB transmission in Shanghai between 1 January 2009 and 31 December 2012 using genotyping and geospatial analyses. Results A total of 367 MDR-TB cases formed the study cohort. Significant differences between MDR-TB cases who were internal migrants and those who were permanent residents were found with regard to age, sex, region, genetic characteristics and treatment outcomes. Permanent residents had a higher transmission rate than internal migrants (OR 3.36, 95%CI 1.86-6.09). Permanent residents and genotypic clustering cases had similar clusters in central downtown and some parts of suburban areas. Most of the clusters of internal migrants were found in rural areas bordering suburban areas. Clusters of genotypic non-clustering cases showed patterns that closely matched those of internal migrants, suggesting acquired drug resistance in migrants. Conclusion In Shanghai, permanent residents were significantly associated with recent transmission of MDR-TB in central downtown areas. Clustered cases of internal migrants in rural areas were most likely to have contracted MDR-TB through acquired resistance.

The present meta-analysis was designed to improve statistical power and review the effects of monoclonal antibodies against PCSK9 on clinical cardiovascular events. PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to May 2017. Studies considered to be eligible were randomized controlled trials about the effects of monoclonal antibodies against PCSK9 on clinical cardiovascular events. The primary endpoint was positively adjudicated cardiovascular events; the secondary endpoint comprised cardiac mortality, myocardial infarction (MI), coronary revascularization, stroke, and hospitalization for unstable angina. We included 20 randomized controlled trials involving 67,934 patients. Monoclonal antibodies against PCSK9 were associated with a significant reduction in positively adjudicated cardiovascular events (relative risk [RR] = 0.87; 95% confidence interval [CI] = 0.81–0.93; z = 4.03; p = 0.000), MI (RR = 0.78; 95% CI = 0.71–0.86; z = 4.96; p = 0.000), coronary revascularization (RR = 0.81, 95% CI = 0.75–0.88; z = 4.93; p = 0.000), and stroke (RR = 0.76, 95% CI = 0.65–0.89; z = 3.47; p = 0.001). Monoclonal antibodies against PCSK9 did not reduce hospitalization rates due to unstable angina. The results of subgroup analysis showed that evolocumab was associated with a lower risk of positively adjudicated cardiovascular events, MI, coronary revascularization, and stroke without reducing cardiac mortality. Alirocumab reduced the incidence of cardiac mortality but not of other cardiovascular events, while bococizumab was associated with a reduced risk of stroke. Monoclonal antibodies against PCSK9 were associated with a lower risk of positively adjudicated cardiovascular events, MI, coronary revascularization, and stroke.

To compare the safety and effectiveness of two different materials (mesh and suture line) used in laparoscopic extraperitoneal uterine suspension.A retrospective observational study.Gynaecology departments in two hospitals in China.Women with symptomatic pelvic organ prolapse (POP) of stage II or higher.The women were divided into two groups according to the two different materials for laparoscopic extraperitoneal uterine suspension: mesh or suture line. The baseline characteristics, perioperative details, complications, objective and subjective indexes of the two groups were compared.The primary outcome was subjective satisfaction rate based upon validated questionnaires. The secondary outcome was objective anatomic assessment with the POP-Q system.No difference was found in baseline characteristics and perioperative details except that there were more cases of cardiovascular disease (CVD) and associated other surgeries in the Line than the Mesh group (36 versus 19, P 0.05; 12 versus 2, P 0.05). Statistically significant improvements were found in anatomical measures of points Aa, Ba, Ap, Bp, C and TVL (P 0.01), as well as functional and quality-of-life measures (P 0.01 for PFDI-20 and PFIQ-7) between both groups. The postoperative PFDI-20, PFIQ-7 and PGI-I scores were not different between two groups (P 0.05). Two cases of deep wound infection were observed in Mesh group at 3-month follow up.Laparoscopic extraperitoneal linear uterine suspension is easy to perform and is associated with fewer mesh-related complications. It is more secure, especially in elderly women and in those with physical complications.Laparoscopic extraperitoneal linear uterine suspension is safe, with fewer mesh-related complications.

Obesity and insulin resistance are risk factors for nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease worldwide. Because no approved medication nor an accurate and noninvasive diagnosis is currently available for NAFLD, there is a clear need to better understand the link between obesity and NAFLD. Lipid accumulation during obesity is known to be associated with oxidative stress and inflammatory activation of liver macrophages (LMs). However, we show that although LMs do not become proinflammatory during obesity, they display signs of oxidative stress. In livers of both humans and mice, antioxidant nuclear factor erythroid 2– related factor 2 (NRF2) was down-regulated with obesity and insulin resistance, yielding an impaired response to lipid accumulation. At the molecular level, a microRNA-targeting NRF2 protein, miR-144, was elevated in the livers of obese insulin-resistant humans and mice, and specific silencing of miR-144 in murine and human LMs was sufficient to restore NRF2 protein expression and the antioxidant response. These results highlight the pathological role of LMs and their therapeutic potential to restore the impaired endogenous antioxidant response in obesity-associated NAFLD. Published (Publication status)

In response to the recent rise in numbers of diabetes patients, many treatments have been developed; but currently, oral antihyperglycemic agents and insulin are still the main clinical treatments. Since current drugs have limitations and harmful side effects, research in alternative treatments has been sought. This article reviews recent research updates of Saskatoon berries (SB), covering its background information, its main active ingredients, its structure, and its function. Flavonoid compounds in Saskatoon berries, in particular flavanol, anthocyanin, and proanthocyanin, possess anti-inflammatory, antitumor, and antidiabetes impacts. The current review synthesizes the latest research on the health benefits of Saskatoon berry in a variety of domains. With further research, SB has the potential to help treat and prevent diabetes in the future.

Nanoscale electron pulses are increasingly in demand, including as probes of nanoscale ultrafast dynamics and for emerging light source and lithography applications. Using electromagnetic simulations, we show that gold plasmonic lenses as multiphoton photoemitters provide unique advantages, including emission from an atomically at surface, nanoscale pulse diameter regardless of laser spot size, and femtosecond-scale response time. We then present fabrication of prototypes with sub-nm roughness via e-beam lithography, as well as electro-optical characterization using cathodoluminescence spectromicroscopy. Finally, we introduce a DC photogun at LBNL built for testing ultrafast photoemitters. We discuss measurement considerations for ultrafast nanoemitters and predict that we can extract tens of pA photocurrent from a single plasmonic lens using a Ti:Sa oscillator. Altogether, this lays the groundwork to develop and test a broad class of plasmon-enhanced ultrafast nanoemitters.

OBJECTIVE Type 2 diabetes is increasing in children worldwide, with Canadian First Nations (FN) children disproportionally affected. The prevalence of gestational diabetes mellitus (GDM) also is increasing. The objective of this study was to evaluate the impact of GDM exposure in utero and FN status on the subsequent risk of type 2 diabetes in offspring in the first 30 years of life. RESEARCH DESIGN AND METHODS In this population-based historical prospective cohort study, we used administrative databases linked to a clinical database to explore the independent association and interaction between GDM and FN status on the subsequent development of type 2 diabetes in offspring. RESULTS Among 321,008 births with a median follow-up of 15.1 years, both maternal GDM and FN status were independently associated with subsequent risk of type 2 diabetes in offspring in the first 30 years of life (hazard ratio 3.03 [95% CI 2.44–3.76; P < 0.0001] vs. 4.86 [95% CI 4.08–5.79; P < 0.0001], respectively). No interaction between GDM and FN status on type 2 diabetes risk was observed. FN status had a stronger impact on the development of type 2 diabetes in offspring than GDM. CONCLUSIONS GDM is an important modifiable risk factor for type 2 diabetes, and its prevention may reduce the prevalence of subsequent type 2 diabetes in offspring. This study adds unique and rigorous evidence to the global public health debate about the impact of GDM on the long-term health of offspring.

Study design: This is a randomized controlled prospective trial with two parallel groups. Objectives: The objective of this study was to determine whether early application of tail nerve electrical stimulation (TANES)-induced walking training can improve the locomotor function. Setting: This study was conducted in SCS Research Center in Colorado, USA. Methods: A contusion injury to spinal cord T10 was produced using the New York University impactor device with a 25 -mm height setting in female, adult Long–Evans rats. Injured rats were randomly divided into two groups (n=12 per group). One group was subjected to TANES-induced walking training 2 weeks post injury, and the other group, as control, received no TANES-induced walking training. Restorations of behavior and conduction were assessed using the Basso, Beattie and Bresnahan open-field rating scale, horizontal ladder rung walking test and electrophysiological test (Hoffmann reflex). Results: Early application of TANES-induced walking training significantly improved the recovery of locomotor function and benefited the restoration of Hoffmann reflex. Conclusion: TANES-induced walking training is a useful method to promote locomotor recovery in rats with spinal cord injury.

Cardiovascular diseases are the major cause of mortality in diabetes patients. Increased levels of glycated low density lipoprotein (glyLDL) are detected in diabetic patients. Endothelial nitric oxide synthase (eNOS) generates nitric oxide, which is responsible to endothelium-dependent vasodilation. The impact of glyLDL on the expression and activity of eNOS in vascular endothelial cells (EC) remains unknown. The present study investigated the effect of glyLDL on the levels of protein, mRNA and activity of eNOS in cultured human umbilical vein EC. The results demonstrated that incubation of EC with physiological concentrations of glyLDL significantly reduced the abundances of eNOS protein in EC with the maximal inhibition at 100μg/ml for 24h. At the optimized condition, glyLDL decreased eNOS mRNA and reduced its activity in EC. Blocking antibody against the receptor for advanced glycation end products (RAGE) prevented glyLDL-induced downregulation of eNOS in EC. GlyLDL increased the translocation of H-Ras from cytoplasm to membrane in EC. Farnesyl-transferase inhibitor-276, an H-Ras antagonist, normalized glyLDL-induced downregulation of eNOS and prevented glyLDL-induced upregulation of H-Ras in EC membrane. Treatment with 4-phenylbutyric acid, an endoplasmic reticulum (ER) stress antagonist, prevented glyLDL-induced eNOS downregulation in EC. The results suggest that diabetes-associated metabolic stress inhibits the production and activity of eNOA in cultured human vascular EC through the activation of RAGE/H-Ras mediated upstream signaling pathway. ER stress induced by glyLDL is possibly involved in eNOS downregulation.

We report an enhancement of low-field, high-frequency magneto-impedance (MI) response and circumferential domain structures of melt-extracted amorphous Co69.25Fe4.25Si13B13.5 microwires by dc Joule annealing. The current amplitudes of 5 mA, 10 mA, and 20 mA were applied to amorphous microwires for different time treatments. The magnetic field dependence of impedance and circumferential domain structure of the microwires were explored using an impedance analyzer over a high frequency range (20 MHz–1000 MHz) and magnetic force microscopy (MFM), respectively. Consequently, the optimum value of 5 mA current for 20 min markedly improved the MI ratio up to 610% (1.7 times of 380% from the as-cast state) at a working frequency of 20 MHz. Moreover, the magnetic field sensitivity has been achieved up to 500%/Oe (more than two times of 225%/Oe from the as-cast one) at a frequency of 40 MHz. MFM images clearly show the development of a well-defined circumferential domain structure of the annealed microwire comparing with the as-cast one. The improvement of the high-frequency MI response in Co-rich amorphous microwires is promising for sensitive magnetic microsensors for low field detection.