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AN3444 Driving LEDs with Constant Current and Sequential Linear LED Drivers

AN3444 Driving LEDs with Constant Current and Sequential Linear LED Drivers




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JBL® Introduces Its First Soundbar with Dolby Atmos, the JBL Bar 9.1 True Wireless Surround Sound

CES 2020, LAS VEGAS – JANUARY 6, 2020 – Movie lovers, listen up. The latest addition to JBL’s popular Bar Series brings the audio experience of a movie theater to your living room. The JBL Bar 9.1 creates true wireless surround sound with crowd-pleasing...




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JBL intros Boombox 2, Bar 9.1 true wireless surround sound




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Slower-moving hurricanes will cause more devastation as world warms

Climate models show that as the world warms, tropical cyclones will travel more slowly, dumping more rain in one place and making high-speed winds batter buildings for longer




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Ocean currents are sweeping microplastics into the deep sea

Slow-moving underwater currents are leading to build ups of microplastics in biologically rich areas on the sea floor




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Breast-Feeding May Lower Breast Cancer Recurrence, Death: Study

Title: Breast-Feeding May Lower Breast Cancer Recurrence, Death: Study
Category: Health News
Created: 4/28/2015 12:00:00 AM
Last Editorial Review: 4/29/2015 12:00:00 AM




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Mindfulness Therapy May Help Ease Recurrent Depression

Title: Mindfulness Therapy May Help Ease Recurrent Depression
Category: Health News
Created: 4/27/2016 12:00:00 AM
Last Editorial Review: 4/28/2016 12:00:00 AM




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Redefining Medical Competencies for an Oral Medicine Specialty Training Curriculum Using a Modified Delphi Technique

This article describes the development of medical competencies for oral medicine specialty training in the UK and Ireland by a collaborative working group using a modified Delphi technique. The current specialty training curriculum for oral medicine (OM) in the UK was developed by a working group including members of the British Society for Oral Medicine (BSOM) and members of the Specialty Advisory Committee for Additional Dental Specialties (SACADS) and adopted by the UK General Dental Council (GDC) in 2010. When the curriculum was developed, the entry requirements for specialty training in OM included undergraduate degrees in both dentistry and medicine. At the time of adoption, the requirement for a medical degree was removed. Medical competencies were assumed to have been delivered in medical undergraduate and postgraduate training. Accordingly, there was a need to define the medical competencies for OM specialty training to benefit trainees, trainers, and assessors. In 2018, a group comprising specialty trainers, recent former specialty trainees, and current specialty trainees in OM held face-to-face meetings in addition to email discussions and developed an updated curriculum document to better reflect the medical competencies required in specialty training. A collaborative modified Delphi approach was used to evaluate medical foundation competencies and to include only those that were considered relevant to OM specialty training. A list of relevant and achievable medical competencies was determined that has been approved by SACADS and will be incorporated into a revised OM curriculum from the UK GDC. The newly agreed-upon document for medical competencies in OM specialty training will serve as a reference for trainees, trainers, and assessors and reflects a successful use of a modified Delphi approach.




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Adaptive Evolution of Geobacter sulfurreducens in Coculture with Pseudomonas aeruginosa

ABSTRACT

Interactions between microorganisms in mixed communities are highly complex, being either syntrophic, neutral, predatory, or competitive. Evolutionary changes can occur in the interaction dynamics between community members as they adapt to coexistence. Here, we report that the syntrophic interaction between Geobacter sulfurreducens and Pseudomonas aeruginosa coculture change in their dynamics over evolutionary time. Specifically, Geobacter sp. dominance increases with adaptation within the cocultures, as determined through quantitative PCR and fluorescence in situ hybridization. This suggests a transition from syntrophy to competition and demonstrates the rapid adaptive capacity of Geobacter spp. to dominate in cocultures with P. aeruginosa. Early in coculture establishment, two single-nucleotide variants in the G. sulfurreducens fabI and tetR genes emerged that were strongly selected for throughout coculture evolution with P. aeruginosa phenazine wild-type and phenazine-deficient mutants. Sequential window acquisition of all theoretical spectra-mass spectrometry (SWATH-MS) proteomics revealed that the tetR variant cooccurred with the upregulation of an adenylate cyclase transporter, CyaE, and a resistance-nodulation-division (RND) efflux pump notably known for antibiotic efflux. To determine whether antibiotic production was driving the increased expression of the multidrug efflux pump, we tested Pseudomonas-derived phenazine-1-carboxylic acid (PHZ-1-CA) for its potential to inhibit Geobacter growth and drive selection of the tetR and fabI genetic variants. Despite its inhibitory properties, PHZ-1-CA did not drive variant selection, indicating that other antibiotics may drive overexpression of the efflux pump and CyaE or that a novel role exists for these proteins in the context of this interaction.

IMPORTANCE Geobacter and Pseudomonas spp. cohabit many of the same environments, where Geobacter spp. often dominate. Both bacteria are capable of extracellular electron transfer (EET) and play important roles in biogeochemical cycling. Although they recently in 2017 were demonstrated to undergo direct interspecies electron transfer (DIET) with one another, the genetic evolution of this syntrophic interaction has not been examined. Here, we use whole-genome sequencing of the cocultures before and after adaptive evolution to determine whether genetic selection is occurring. We also probe their interaction on a temporal level and determine whether their interaction dynamics change over the course of adaptive evolution. This study brings to light the multifaceted nature of interactions between just two microorganisms within a controlled environment and will aid in improving metabolic models of microbial communities comprising these two bacteria.




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A large Taenidium burrow from the Upper Carboniferous of Corrie, Isle of Arran, and remarks on the association of Taenidium burrows and Diplichnites trails

Large un-walled backfilled burrows of the Taenidium type are known from Paleozoic deltaic marine environments worldwide where they are often associated with Diplichnites trackways. The latter are generally attributed to arthropleurid myriapods and it may be that the burrows were also made by these animals. Here we describe a Taenidium burrow from the Limestone Coal Formation of the Isle of Arran, a formation that also hosts a well-known example of Diplichnites, supporting the association of the two types of trace fossil and extending their known co-occurrence upward into the Upper Carboniferous.




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The Occurrence of Sulfated Salicinoids in Poplar and Their Formation by Sulfotransferase1

Salicinoids form a specific class of phenolic glycosides characteristic of the Salicaceae. Although salicinoids accumulate in large amounts and have been shown to be involved in plant defense, their biosynthesis is unclear. We identified two sulfated salicinoids, salicin-7-sulfate and salirepin-7-sulfate, in black cottonwood (Populus trichocarpa). Both compounds accumulated in high amounts in above-ground tissues including leaves, petioles, and stems, but were also found at lower concentrations in roots. A survey of salicin-7-sulfate and salirepin-7-sulfate in a subset of poplar (Populus sp.) and willow (Salix sp.) species revealed a broader distribution within the Salicaceae. To elucidate the formation of these compounds, we studied the sulfotransferase (SOT) gene family in P. trichocarpa (PtSOT). One of the identified genes, PtSOT1, was shown to encode an enzyme able to convert salicin and salirepin into salicin-7-sulfate and salirepin-7-sulfate, respectively. The expression of PtSOT1 in different organs of P. trichocarpa matched the accumulation of sulfated salicinoids in planta. Moreover, RNA interference-mediated knockdown of SOT1 in gray poplar (Populus x canescens) resulted in decreased levels of sulfated salicinoids in comparison to wild-type plants, indicating that SOT1 is responsible for their formation in planta. The presence of a nonfunctional SOT1 allele in black poplar (Populus nigra) was shown to correlate with the absence of salicin-7-sulfate and salirepin-7-sulfate in this species. Food choice experiments with leaves from wild-type and SOT1 knockdown trees suggest that sulfated salicinoids do not affect the feeding preference of the generalist caterpillar Lymantria dispar. A potential role of the sulfated salicinoids in sulfur storage and homeostasis is discussed.




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Author response: Functional neurologic disorders: Bringing the informal and hidden curriculum to light

Dr. Sethi raises an excellent point about the term functional neurologic disorder (FND) in his comment on the editorial.1 It seems clear that reticence to use the term functional creates the ambiguity he mentions. Medically unexplained symptoms, categorized in the international classification of diseases as undifferentiated somatoform disorders, are a diagnosis that many providers are loathed to give. Whether that is because of concern about missing a diagnosis is not clear. Having evaluated and treated more than 400 of these individuals in the FND clinic at the University of Colorado, I can attest to the fact that patients arrive confused about their diagnosis. Multiple incorrect diagnoses, as Dr. Sethi points out, pack the medical histories of patients with FND, leading doctors and patients astray. I believe that the commentary by Perez et al.2 gives us the best chance for a way forward, by teaching a new generation of residents and fellows how to approach patients in a nonjudgmental and open-minded fashion. It took 30 years to add Functional Neurologic Disorder to the Diagnostic and Statistical Manual, and it is still parenthetical to the term Conversion.3 Stripping the diagnosis of FND of its stigma and empowering care providers to rule in functional disorders is an actionable step which should be taken.




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Reader response: Functional neurologic disorders: Bringing the informal and hidden curriculum to light

I read with interest the editorial by Strom1 about functional neurologic disorders (FNDs). As a treating physician, I have struggled with the multiple diagnostic labels attached to these patients by physicians of different medical specialties during the course of their clinical disease presentation. A neurologist may assign a patient who presents with chronic fatigue the diagnostic labels of narcolepsy, idiopathic hypersomnia, or chronic Lyme disease. A rheumatologist may assign the label of collagen vascular disease, and a psychiatrist may diagnose depression. This diagnostic ambiguity is troublesome for patients and clinicians alike. I contend that even the term FND needs to be revisited. A patient should be broadly labeled as having a functional disorder and only after characterization sublabeled and referred to an appropriate specialty physician.




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Phenotypic Plasticity: From Theory and Genetics to Current and Future Challenges [Perspectives]

Phenotypic plasticity is defined as the property of organisms to produce distinct phenotypes in response to environmental variation. While for more than a century, biologists have proposed this organismal feature to play an important role in evolution and the origin of novelty, the idea has remained contentious. Plasticity is found in all domains of life, but only recently has there been an increase in empirical studies. This contribution is intended as a fresh view and will discuss current and future challenges of plasticity research, and the need to identify associated molecular mechanisms. After a brief summary of conceptual, theoretical, and historical aspects, some of which were responsible for confusion and contention, I will formulate three major research directions and predictions for the role of plasticity as a facilitator of novelty. These predictions result in a four-step model that, when properly filled with molecular mechanisms, will reveal plasticity as a major factor of evolution. Such mechanistic insight must be complemented with comparative investigations to show that plasticity has indeed created novelty and innovation. Together, such studies will help develop a true developmental evolutionary biology.




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Complement Deficiencies Result in Surrogate Pathways of Complement Activation in Novel Polygenic Lupus-like Models of Kidney Injury [AUTOIMMUNITY]

Key Points

  • Novel TM lupus mouse strains develop spontaneous nephritis.

  • In C1q deficiency, kidney complement activation likely occurred via the LP.

  • In C3 deficiency, coagulation cascade contributed to kidney complement activation.




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    De Novo Purine Biosynthesis Is Required for Intracellular Growth of Staphylococcus aureus and for the Hypervirulence Phenotype of a purR Mutant [Cellular Microbiology: Pathogen-Host Cell Molecular Interactions]

    Staphylococcus aureus is a noted human and animal pathogen. Despite decades of research on this important bacterium, there are still many unanswered questions regarding the pathogenic mechanisms it uses to infect the mammalian host. This can be attributed to it possessing a plethora of virulence factors and complex virulence factor and metabolic regulation. PurR, the purine biosynthesis regulator, was recently also shown to regulate virulence factors in S. aureus, and mutations in purR result in derepression of fibronectin binding proteins (FnBPs) and extracellular toxins, required for a so-called hypervirulent phenotype. Here, we show that hypervirulent strains containing purR mutations can be attenuated with the addition of purine biosynthesis mutations, implicating the necessity for de novo purine biosynthesis in this phenotype and indicating that S. aureus in the mammalian host experiences purine limitation. Using cell culture, we showed that while purR mutants are not altered in epithelial cell binding, compared to that of wild-type (WT) S. aureus, purR mutants have enhanced invasion of these nonprofessional phagocytes, consistent with the requirement of FnBPs for invasion of these cells. This correlates with purR mutants having increased transcription of fnb genes, resulting in higher levels of surface-exposed FnBPs to promote invasion. These data provide important contributions to our understanding of how the pathogenesis of S. aureus is affected by sensing of purine levels during infection of the mammalian host.




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    Improved surrogates in inertial confinement fusion with manifold and cycle consistencies [Computer Sciences]

    Neural networks have become the method of choice in surrogate modeling because of their ability to characterize arbitrary, high-dimensional functions in a data-driven fashion. This paper advocates for the training of surrogates that are 1) consistent with the physical manifold, resulting in physically meaningful predictions, and 2) cyclically consistent with...




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    Structural basis for Zika envelope domain III recognition by a germline version of a recurrent neutralizing antibody [Biochemistry]

    Recent epidemics demonstrate the global threat of Zika virus (ZIKV), a flavivirus transmitted by mosquitoes. Although infection is usually asymptomatic or mild, newborns of infected mothers can display severe symptoms, including neurodevelopmental abnormalities and microcephaly. Given the large-scale spread, symptom severity, and lack of treatment or prophylaxis, a safe and...




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    Oxygen supply capacity in animals evolves to meet maximum demand at the current oxygen partial pressure regardless of size or temperature [RESEARCH ARTICLE]

    Brad A. Seibel and Curtis Deutsch

    The capacity to extract oxygen from the environment and transport it to respiring tissues in support of metabolic demand reportedly has implications for species’ thermal tolerance, body-size, diversity and biogeography. Here we derive a quantifiable linkage between maximum and basal metabolic rate and their oxygen, temperature and size dependencies. We show that, regardless of size or temperature, the physiological capacity for oxygen supply precisely matches the maximum evolved demand at the highest persistently available oxygen pressure and this is the critical PO2 for the maximum metabolic rate. For most terrestrial and shallow-living marine species, this "Pcrit-max" is the current atmospheric pressure, 21 kPa. Any reduction in oxygen partial pressure from current values will result in a calculable decrement in maximum metabolic performance. However, oxygen supply capacity has evolved to match demand across temperatures and body sizes and so does not constrain thermal tolerance or cause the well-known reduction in mass-specific metabolic rate with increasing body mass. The critical oxygen pressure for resting metabolic rate, typically viewed as an indicator of hypoxia tolerance, is, instead, simply a rate-specific reflection of the oxygen supply capacity. A compensatory reduction in maintenance metabolic costs in warm-adapted species constrains factorial aerobic scope and the critical PO2 to a similar range, between ~2 and 6, across each species’ natural temperature range. The simple new relationship described here redefines many important physiological concepts and alters their ecological interpretation.




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    18F-rhPSMA-7 PET for the Detection of Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy

    18F-labeled prostate-specific membrane antigen (PSMA) PET tracers are increasingly used in preference to 68Ga-PSMA-11 for restaging biochemical recurrence (BCR) of prostate cancer. They are associated with longer half-lives, larger-scale production, and lower positron range than their 68Ga-labeled counterparts. Here, we describe the efficacy of an 18F-labeled radiohybrid PSMA, rhPSMA-7, a novel theranostic PSMA-targeting agent for imaging BCR of prostate cancer. Methods: Datasets from 261 consecutive patients with noncastrate BCR after radical prostatectomy who underwent 18F-rhPSMA-7 PET/CT at our institution between June 2017 and March 2018 were reviewed retrospectively. All lesions suspected of being recurrent prostate cancer were recorded. The detection rate for sites of presumed recurrence was correlated with patients’ prostate-specific antigen (PSA) level, primary Gleason score, and prior therapy (androgen deprivation therapy and external-beam radiation therapy). Results: The 261 patients had a median PSA level of 0.96 ng/mL (range, 0.01–400 ng/mL). The median injected activity of 18F-rhPSMA-7 was 336 MBq, with a median uptake time of 76 min. In total, 211 patients (81%) showed pathologic findings on 18F-rhPSMA-7 PET/CT. The detection rates were 71% (42/59), 86% (44/51), 86% (42/49), and 95% (76/80) at PSA levels of 0.2 to <0.5 ng/mL, 0.5 to <1 ng/mL, 1 to <2 ng/mL, and ≥2 ng/mL, respectively. In 32% patients (7/22) with a PSA of less than 0.2 ng/mL, suggestive lesions were present. 18F-rhPSMA-7 PET/CT revealed local recurrence in 43% of patients (113). Lymph node metastases were present in the pelvis in 42% of patients (110), in the retroperitoneum in 17% (45), and in a supradiaphragmatic location in 8.0% (21). Bone and visceral metastases were detected in 21% (54) and 3.8% (10), respectively. Detection efficacy was not influenced by prior external-beam radiation therapy (79.1% vs. 82.1%, P = 0.55), androgen deprivation therapy within the 6 mo preceding imaging (80.6% vs. 80.9%, P = 0.54), or primary Gleason score (77.9% for ≤7 vs. 82.6% for ≥8, P = 0.38). Conclusion: 18F-rhPSMA-7 PET/CT offers high detection rates in early BCR after radical prostatectomy, especially among patients with low PSA values.




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    Genetic Association Reveals Protection against Recurrence of Clostridium difficile Infection with Bezlotoxumab Treatment

    ABSTRACT

    Bezlotoxumab is a human monoclonal antibody against Clostridium difficile toxin B, indicated to prevent recurrence of C. difficile infection (rCDI) in high-risk adults receiving antibacterial treatment for CDI. An exploratory genome-wide association study investigated whether human genetic variation influences bezlotoxumab response. DNA from 704 participants who achieved initial clinical cure in the phase 3 MODIFY I/II trials was genotyped. Single nucleotide polymorphisms (SNPs) and human leukocyte antigen (HLA) imputation were performed using IMPUTE2 and HIBAG, respectively. A joint test of genotype and genotype-by-treatment interaction in a logistic regression model was used to screen genetic variants associated with response to bezlotoxumab. The SNP rs2516513 and the HLA alleles HLA-DRB1*07:01 and HLA-DQA1*02:01, located in the extended major histocompatibility complex on chromosome 6, were associated with the reduction of rCDI in bezlotoxumab-treated participants. Carriage of a minor allele (homozygous or heterozygous) at any of the identified loci was related to a larger difference in the proportion of participants experiencing rCDI versus placebo; the effect was most prominent in the subgroup at high baseline risk for rCDI. Genotypes associated with an improved bezlotoxumab response showed no association with rCDI in the placebo cohort. These data suggest that a host-driven, immunological mechanism may impact bezlotoxumab response. Trial registration numbers are as follows: NCT01241552 (MODIFY I) and NCT01513239 (MODIFY II).

    IMPORTANCE Clostridium difficile infection is associated with significant clinical morbidity and mortality; antibacterial treatments are effective, but recurrence of C. difficile infection is common. In this genome-wide association study, we explored whether host genetic variability affected treatment responses to bezlotoxumab, a human monoclonal antibody that binds C. difficile toxin B and is indicated for the prevention of recurrent C. difficile infection. Using data from the MODIFY I/II phase 3 clinical trials, we identified three genetic variants associated with reduced rates of C. difficile infection recurrence in bezlotoxumab-treated participants. The effects were most pronounced in participants at high risk of C. difficile infection recurrence. All three variants are located in the extended major histocompatibility complex on chromosome 6, suggesting the involvement of a host-driven immunological mechanism in the prevention of C. difficile infection recurrence.




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    Accuracy of the Ottawa score in risk stratification of recurrent venous thromboembolism in patients with cancer-associated venous thromboembolism: a systematic review and meta-analysis

    In patients with cancer-associated venous thromboembolism, knowledge of the estimated rate of recurrent events is important for clinical decision-making regarding anticoagulant therapy. The Ottawa score is a clinical prediction rule designed for this purpose, stratifying patients according to their risk of recurrent venous thromboembolism during the first six months of anticoagulation. We conducted a systematic review and meta-analysis of studies validating either the Ottawa score in its original or modified versions. Two investigators independently reviewed the relevant articles published from 1st June 2012 to 15th December 2018 and indexed in MEDLINE and EMBASE. Nine eligible studies were identified; these included a total of 14,963 patients. The original score classified 49.3% of the patients as high-risk, with a sensitivity of 0.7 [95% confidence interval (CI): 0.6-0.8], a 6-month pooled rate of recurrent venous thromboembolism of 18.6% (95%CI: 13.9-23.9). In the low-risk group, the recurrence rate was 7.4% (95%CI: 3.4-12.5). The modified score classified 19.8% of the patients as low-risk, with a sensitivity of 0.9 (95%CI: 0.4-1.0) and a 6-month pooled rate of recurrent venous thromboembolism of 2.2% (95%CI: 1.6-2.9). In the high-risk group, recurrence rate was 10.2% (95%CI: 6.4-14.6). Limitations of our analysis included type and dosing of anticoagulant therapy. We conclude that new therapeutic strategies are needed in patients at high risk for recurrent cancer-associated venous thromboembolism. Low-risk patients, as per the modified score, could be good candidates for oral anticoagulation. (This systematic review was registered with the International Prospective Registry of Systematic Reviews as: PROSPERO CRD42018099506).




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    5-formylcytosine and 5-hydroxymethyluracil as surrogate markers of TET2 and SF3B1 mutations in myelodysplastic syndrome, respectively




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    Methylated Vnn1 at promoter regions induces asthma occurrence via the PI3K/Akt/NF{kappa}B-mediated inflammation in IUGR mice [RESEARCH ARTICLE]

    Yan Xing, Hongling Wei, Xiumei Xiao, Zekun Chen, Hui Liu, Xiaomei Tong, and Wei Zhou

    Infants with intrauterine growth retardation (IUGR) have a high risk of developing bronchial asthma in childhood, but the underlying mechanisms remain unclear. This study aimed to disclose the role of vascular non-inflammatory molecule 1 (vannin-1, encoded by the Vnn1 gene) and its downstream signaling in IUGR asthmatic mice induced by ovalbumin. Significant histological alterations and an increase of vannin-1 expression were revealed in IUGR asthmatic mice, accompanied by elevated methylation of Vnn1 promoter regions. In IUGR asthmatic mice, we also found (i) a direct binding of HNF4α and PGC1α to Vnn1 promoter by ChIP assay; (ii) a direct interaction of HNF4α with PGC1α; (iii) upregulation of phospho-PI3K p85/p55 and phospho-AktSer473 and downregulation of phospho-PTENTyr366, and (iv) an increase in nuclear NFB p65 and a decrease in cytosolic IB-α. In primary cultured bronchial epithelial cells derived from the IUGR asthmatic mice, knockdown of Vnn1 prevented upregulation of phospho-AktSer473 and an increase of reactive oxygen species (ROS) and TGF-β production. Taken together, we demonstrate that elevated vannin-1 activates the PI3K/Akt/NFB signaling pathway, leading to ROS and inflammation reactions responsible for asthma occurrence in IUGR individuals. We also disclose that interaction of PGC1α and HNF4α promotes methylation of Vnn1 promoter regions and then upregulates vannin-1 expression.




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    Can We Improve Current Cancer Screening Programs?

    Cancer continues to be one of the leading causes of morbidity and mortality in the US. Although the treatment of cancer has evolved over the past decades with the use of targeted therapies and immunotherapy, many of these new treatments are expensive and are not readily available to everyone. Moreover, the recent success with treatment advances are not generalized to all cancer types, as some cancers continue to be devastating without significant progress in treatment options. Hence, early detection through population screening remains a critical armament against cancer.




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    Recurrent pneumothorax, skin lesions and frequent urination

    A 25-year-old male is admitted with complaints of dry cough for the past 5 years, and increased thirst, urinary frequency and output for the past 18 months. He also complains of shortness of breath on climbing a flight of stairs, and itchy lesions on the scalp and back for the past 2–3 months. There is no history of bone pain or abdominal pain. He has history of bilateral recurrent pneumothoraxes, twice on the right and once on the left side, in the past month. Pleurodesis with povidone iodine is performed on left side and the patient is transferred to your hospital with persistent right pneumothorax with air leak, with an intercostal drainage tube in situ. The patient is a never-smoker with no family history of pneumothorax. On general examination, he has small papules, 1–2 mm in diameter, with scaling over scalp and back. Onycholysis, onychoschisis and subungual splinter haemorrhages are present (figure 1).




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    Recurrent Aphthous Stomatitis: Consider Anemia and Celiac Disease




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    Antifungal Susceptibility Testing: Current Approaches [Reviews]

    Although not as ubiquitous as antibacterial susceptibility testing, antifungal susceptibility testing (AFST) is a tool of increasing importance in clinical microbiology laboratories. The goal of AFST is to reliably produce MIC values that may be used to guide patient therapy, inform epidemiological studies, and track rates of antifungal drug resistance. There are three methods that have been standardized by standards development organizations: broth dilution, disk diffusion, and azole agar screening for Aspergillus. Other commonly used methods include gradient diffusion and the use of rapid automated instruments. Novel methodologies for susceptibility testing are in development. It is important for laboratories to consider not only the method of testing but also the interpretation (or lack thereof) of in vitro data.




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    Prospective Evaluation of Bone Metabolic Markers as Surrogate Markers of Response to Radium-223 Therapy in Metastatic Castration-resistant Prostate Cancer

    Purpose:

    Radium-223 is approved for metastatic castration-resistant prostate cancer (mCRPC) based on improved overall survival, and delay in skeletal related events. However, it is not associated with PSA or radiographic response, which poses a challenge in real-time assessment of its efficacy. Surrogate markers of treatment outcomes may facilitate tailoring treatment duration with radium-223, by limiting the duration of therapy with radium-223 in these patients. Here, we sought to investigate the utility of bone metabolic markers (BMMs) as surrogate markers of response to radium-223 in mCRPC.

    Patients and Methods:

    A prospective phase II trial of radium-223 plus enzalutamide (RE) versus enzalutamide alone was designed to assess surrogacy of BMMs with respect to response to radium-223. Enzalutamide was used as a comparator in lieu of placebo due to the progressive disease. Co-primary endpoints were relative change in serum BMM N-telopeptide (NTP) levels from baseline to 6 months between the two arms and safety and feasibility of the combination.

    Results:

    Thirty-nine men were randomized to RE (n = 27) or enzalutamide (n = 12). Combination was safe and feasible. Primary endpoint was met. A statistically significant relative change to NTP ratios between arms (0.64, 95% confidence interval, 0.51–0.81; P = 0.00048) favored RE versus enzalutamide. Overall, BMMs decreased with the RE therapy compared with enzalutamide. Improved PSA response rate in RE versus enzalutamide (P = 0.024), correlated with decline in BMMs.

    Conclusions:

    BMMs declined significantly with combination therapy, and were associated with improved outcomes. Upon external validation, BMMs may emerge as surrogate markers to monitor treatment with radium-223 in real-time.




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    Co-occurrence of Plasmid-Mediated Tigecycline and Carbapenem Resistance in Acinetobacter spp. from Waterfowls and Their Neighboring Environment [Epidemiology and Surveillance]

    Tigecycline serves as one of the antibiotics of last resort to treat multidrug-resistant (including carbapenem-resistant) pathogens. However, the recently emerged plasmid-mediated tigecycline resistance mechanism, Tet(X), challenges the clinical efficacy of this class of antibiotics. In this study, we detected 180 tet(X)-harboring Acinetobacter isolates (8.9%, n = 180) from 2,018 samples collected from avian farms and adjacent environments in China. Eighteen tet(X)-harboring isolates (10.0%) were found to cocarry the carbapenemase gene blaNDM-1, mostly from waterfowl samples (94.4%, 17/18). Interestingly, among six Acinetobacter strains, tet(X) and blaNDM-1 were found to colocalize on the same plasmids. Moreover, whole-genome sequencing (WGS) revealed a novel orthologue of tet(X) in the six isolates coharboring tet(X) and blaNDM-1. Inverse PCR suggested that the two tet(X) genes form a single transposable unit and may be cotransferred. Sequence comparison between six tet(X)- and blaNDM-1-coharboring plasmids showed that they shared a highly homologous plasmid backbone even though they were isolated from different Acinetobacter species (three from Acinetobacter indicus, two from Acinetobacter schindleri, and one from Acinetobacter lwoffii) from various sources and from different geological regions, suggesting the horizontal genetic transfer of a common tet(X)- and blaNDM-1-coharboring plasmid among Acinetobacter species in China. Emergence and spread of such plasmids and strains are of great clinical concern, and measures must be implemented to avoid their dissemination.




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    Novel Insights into Plasmodium vivax Therapeutic Failure: CYP2D6 Activity and Time of Exposure to Malaria Modulate the Risk of Recurrence [Epidemiology and Surveillance]

    Plasmodium vivax relapse is one of the major causes of sustained global malaria transmission. Primaquine (PQ) is the only commercial drug available to prevent relapses, and its efficacy is dependent on metabolic activation by cytochrome P450 2D6 (CYP2D6). Impaired CYP2D6 function, caused by allelic polymorphisms, leads to the therapeutic failure of PQ as a radical cure for P. vivax malaria. Here, we hypothesized that the host immune response to malaria parasites modulates susceptibility to P. vivax recurrences in association with CYP2D6 activity. We performed a 10-year retrospective study by genotyping CYP2D6 polymorphisms in 261 malaria-exposed individuals from the Brazilian Amazon. The immune responses against a panel of P. vivax blood-stage antigens were evaluated by serological assays. We confirmed our previous findings, which indicated an association between impaired CYP2D6 activity and a higher risk of multiple episodes of P. vivax recurrence (risk ratio, 1.75; 95% confidence interval [CI], 1.2 to 2.6; P = 0.0035). An important finding was a reduction of 3% in the risk of recurrence (risk ratio, 0.97; 95% CI, 0.96 to 0.98; P < 0.0001) per year of malaria exposure, which was observed for individuals with both reduced and normal CYP2D6 activity. Accordingly, subjects with long-term malaria exposure and persistent antibody responses to various antigens showed fewer episodes of malaria recurrence. Our findings have direct implications for malaria control, since it was shown that nonimmune individuals who do not respond adequately to treatment due to reduced CYP2D6 activity may present a significant challenge for sustainable progress toward P. vivax malaria elimination.




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    Efficacy and Safety of Flow-Diverter Therapy for Recurrent Aneurysms after Stent-Assisted Coiling [INTERVENTIONAL]

    BACKGROUND AND PURPOSE:

    Flow-diverter treatment for previously stented aneurysms has been reported to be less effective and prone to complications. In this study, we evaluated the effectiveness and safety of flow diverters for recurrent aneurysms after stent-assisted coiling.

    MATERIALS AND METHODS:

    Patients who underwent flow-diverter placement for recurrent aneurysms after stent-assisted coiling between March 2015 and March 2019 were recruited. Clinical and radiographic characteristics and clinical and angiographic outcomes were retrospectively evaluated.

    RESULTS:

    Among 133 patients who underwent flow-diverter insertion, 17 (male/female ratio = 5:12; mean age, 53.8 years) were treated for recurrent aneurysms after stent placement with (n = 16) or without (n = 1) coiling. Eight patients initially presented with subarachnoid hemorrhage; 7, with headache; and 2, with visual field defects. Angiographic morphology included large/giant saccular in 12 patients, dissecting in 2, fusiform in 1, traumatic pseudoaneurysm in 1, and ruptured blood blister-like aneurysm in 1. The duration between the first treatment and flow-diverter placement ranged from 2 weeks to 15 months (median, 6 months). Flow-diverter placement was successful in all cases without any complications. All patients had favorable outcomes (mRS, 0–2), without any newly appearing symptoms. Aneurysms were followed up with conventional angiography at least once in 6–18 months. Sixteen aneurysms showed complete occlusion, and 1 aneurysm was enlarged.

    CONCLUSIONS:

    Results from this case series investigating flow-diverter placement for recurrent aneurysms after stent-assisted coiling suggested that the procedure is safe and effective. Further study in a larger population may be warranted.




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    RPGCast – Episode 470: “Into The Turret!”

    Armadillos that look like hedgehogs. Chocobos that cheat. Monsters that invade. And squirrels that ride cat skeletons. It’s a really weird week. It also seems...




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    Selah and the Spades review – teen cliques drama balances satire and surrealism

    This uncanny story of preppy drug dealers has a touch of Heathers and a bit of Bret Easton Ellis, and an intriguing take on what high school is really like

    Tayarisha Poe, like her partial namesake, has a gift for the uncanny. She is the photographer and film-maker behind this feature debut, which began as an online multimedia project and was developed as a conventional movie through the Sundance screenwriters and directors labs. What has emerged is an intriguing, opaque, tonally elusive story that seems weirdly unfinished. It is set in a privileged high school – a world of ivy-covered stone buildings and shady quadrangles where rich kids are separated into malign and mutually hostile cliques. It has a touch of Donna Tartt and Bret Easton Ellis, a hint of Heathers and a bit of the elegant, disdainful satire of Dear White People.

    Somehow, though, it is odder, more stylised and contrived, always holding out the possibility that it is set in the future, or in an alternative present on some other planet, or inside the head of one of its characters who is having a disturbing dream – the kind that ends just as it is about to give up its meaning. Right until the closing credits, I half-expected the face of each person on screen to flip upwards, revealing a Stepford-like set of dials.

    Continue reading...




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    Coronavirus Lockdown 3.0: Suspension of labour laws by fiat can only be an immediate-term response to the current crisis

    There has been talk for some time now about easing labour laws, already seen in industry circles as being too rigid and acting as a drag on growth, specifically to facilitate emerging from the lockdown. And it’s not just a question of emerging from it, there’s also the issue of surviving what looks like being a brutal and prolonged global economic downturn. It was reported on Friday that ordinances were being issued in some states.








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    As world shelters, scientists raise alarm on another threat: An active hurricane season

    The season officially begins June 1, but some meteorologists who have been tracking ocean and atmospheric dynamics over the past few months say conditions are ripe for storms.




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    Surrey Police use drone to break up gatherings during coronavirus lockdown

    Follow our live updates HERE Coronavirus: the symptoms




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    The Londoner: &apos;Stolen Van Gogh now underworld currency&apos;

    In today's Diary: What will happen to the stolen Van Gogh? / Adam Macqueen on unorthodox writer's block / Opera stars raising money for musicians / Geoffrey Cox's unfortunate Easter reading




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    Second wave of coronavirus in US could be worse than current outbreak, top health expert warns

    A second wave of coronavirus cases could put an "unimaginable strain" on the US healthcare system this winter, the country's top health official has warned.




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    Couple at sea reveal &apos;surreal&apos; experience of learning about coronavirus pandemic after landing at Caribbean island

    A couple who were living their dream of sailing across the Atlantic have shared their "shock" of returning to land and hearing the news about the global coronavirus pandemic.




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    Murder probe after 88-year-old man found dead at home in Godstone, Surrey

    A murder probe has been launched after an 88-year-old man was found dead at a property in Surrey.




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    Microplastic pollution crisis threatens biodiversity &apos;more than is currently recognised&apos;, research shows

    Microplastics pollution is causing disruption and behavioural changes among hermit crab populations, researchers have claimed.




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    Man charged with murder after 88-year-old widower died from head injury in quiet Surrey village

    A man has been charged with murder after the death of an 88-year-old widower in a quiet English village.




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    England&apos;s first NHS coronavirus recovery hospital named after pioneering nurse opens in Surrey

    A hospital set up to care for people recovering from Covid-19 will be named after the pioneering nurse Mary Seacole to pay tribute to nurses on the frontline of the coronavirus pandemic.




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    Al Murray on WWII-coronavirus parallels: ‘It was exactly the debate that’s going on now’

    We speak to the historian James Holland - and the comedian Al Murray - who together present the weekly World War Two podcast We Have Ways of Making You Talk




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    Which Cryptocurrencies to Mine in 2020

    So, you have decided to start mining this year? This is an excellent way to earn some additional money, but with so many cryptocurrencies on the market, it can be hard to choose the one to mine. Mining can be tempting, but it involves investment in the hardware and software that will support it, hence, […]

    The post Which Cryptocurrencies to Mine in 2020 appeared first on Chart Attack.




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    Fort McMurray: Shopping time!

    By Brady Tighe We’re now officially in the aftermath phase of the northern Alberta wildfire crisis. The fire is long gone, and everyone with a home to return to is back in its cozy confines. The money has been raised, the relief cheques have been sent out, the insurance claims are in, the liquor stores are operational, and […]