Notes

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aregivers' perspectives and experiences of research participation with impaired decision-making capacity require investigation in a greater range of countries and conditions other than dementia, and dissemination through more varied media.
Thirdhand smoke (THS) is ultrafine particulate matter and residue resulting from tobacco combustion, with implications for health-related harm (eg, impaired wound healing), particularly among hospitalized infants. Project aims were to characterize nicotine (THS proxy) transported on neonatal intensive care unit (NICU) visitors and deposited on bedside furniture, as well as infant exposure.

Cross-sectional data were collected from participants in a metropolitan NICU. Participants completed a survey and carbon monoxide breath sample, and 41.9% (n = 88) of participants (n = 210) were randomly selected for finger-nicotine wipes during a study phase when all bedside visitors were screened for nicotine use and finger-nicotine levels. During an overlapping study phase, 80 mother-infant dyads consented to bedside furniture-nicotine wipes and an infant urine sample (for cotinine analyses).

Most nonstaff visitors' fingers had nicotine above the limit of quantification (>LOQ; 61.9%). Almost all bedside furnitur had detectable levels of urinary cotinine during NICU hospitalizations. Results justify further research to better protect infants from unintended THS exposure while hospitalized.
CONCUR is a standalone tool for codon usage analysis in ribosome profiling experiments. CONCUR uses the aligned reads in BAM format to estimate codon counts at the ribosome E-, P-, and A-sites and at flanking positions.

CONCUR is written in Perl and is freely available at https//github.com/susbo/concur.

Supplementary data are available at Bioinformatics online.
Supplementary data are available at Bioinformatics online.
Vast majority of human genetic disorders are associated with mutations that affect protein-protein interactions by altering wild type binding affinity. Therefore, it is extremely important to assess the effect of mutations on protein-protein binding free energy to assist the development of therapeutic solutions. Currently the most popular approaches use structural information to deliver the predictions, which precludes them to be applicable on genome-scale investigations. Indeed, with the progress of genomic sequencing, researchers are frequently dealing with assessing effect of mutations for which there is no structure available.

Here we report a Gradient Boosting Decision Tree (GBDT) machine learning algorithm, the SAAMBE-SEQ, which is completely sequence-based and does not require structural information at all. SAAMBE-SEQ utilizes 80 features representing evolutionary information, sequence-based features and change of physical properties upon mutation at the mutation site. The approach is shown to achieve Pearson correlation coefficient (PCC) of 0.83 in 5-fold cross validation in a benchmarking test against experimentally determined binding free energy change (ΔΔG). Further a blind test (no-STRUC) is compiled collecting experimental ΔΔG upon mutation for protein complexes for which structure is not available and used to benchmark SAAMBE-SEQ resulting in PCC in the range of 0.37 to 0.46. The accuracy of SAAMBE-SEQ method is found to be either better or comparable to most advanced structure-based methods. SAAMBE-SEQ is very fast, available as webserver and stand-alone code, and indeed utilizes only sequence information, and thus it is applicable for genome-scale investigations to study the effect of mutations on protein-protein interactions.

SAAMBE-SEQ is available at http//compbio.clemson.edu/saambe_webserver/indexSEQ.php#started.

Supplementary data are available at Bioinformatics online.
Supplementary data are available at Bioinformatics online.
This review investigates the contribution of discursive approaches to the study of ageism in working life. It looks back on the 50 years of research on ageism and the body of research produced by the discursive turn in social science and gerontology.

This study followed the five-step scoping review protocol to define gaps in the knowledge on ageism in working life from a discursive perspective. 851 papers were extracted from electronic databases and, according to inclusion and exclusion criteria, 39 papers were included in the final review.

The selected articles were based on discursive approaches and included study participants along the full continuum of working life (workers, retirees, jobseekers, students in training). Three main themes representing the focal point of research were identified, namely, experiences of ageism, social construction of age and ageism, and strategies to tackle (dilute) ageism.

Discursive research provides undeniable insights into how participants experience ageism in woron between age and other social categories. Further research in these areas can deepen our understanding of how age and ageism are constructed and can inform policies about ways of disentangling them in working life.
The Aspergillus Galactomannan Lateral Flow Assay (LFA) is a rapid test for the diagnosis of invasive aspergillosis (IA) that has been almost exclusively evaluated in patients with hematologic malignancies. An automated digital cube reader which allows for quantification of results has recently been added to the test kits.

We performed a retrospective multicenter study on bronchoalveolar lavage fluid (BALF) samples obtained from 296 patients with various underlying diseases (65% without underlying hematological malignancy) who had BALF galactomannan (GM) ordered between 2013 and 2019 at the University of California San Diego, the Medical University of Graz, Austria, and the Mannheim University Hospital, Germany.

Cases were classified as proven (n=2), probable (n=56), putative (n=30), possible (n=45), and no IA (n=162). The LFA showed an area under the curve (AUC) of 0.865 (95% CI 0.815-0.916) for differentiating proven/probable or putative IA versus no IA, with a sensitivity of 74% and a specificity of 83% at an optical density index cut-off of 1.5. After exclusion of GM as mycological criterion for case classification, diagnostic performance of the LFA was highly similar to GM testing (AUC 0.892 versus 0.893, respectively). LFA performance was consistent across different patient cohorts and centers.

In this multicenter study the LFA assay from BALF demonstrated good diagnostic performance for IA that was consistent across patient cohorts and locations. The LFA may serve a role as a rapid test that may replace conventional GM testing in settings where GM results are not rapidly available.
In this multicenter study the LFA assay from BALF demonstrated good diagnostic performance for IA that was consistent across patient cohorts and locations. The LFA may serve a role as a rapid test that may replace conventional GM testing in settings where GM results are not rapidly available.Decidualization involves the proliferation and differentiation of fibroblast-like endometrial stromal cells into epithelioid-shaped and secretory 'decidual' cells in response to steroid hormones. Human decidual cells produce insulin-like growth factor-binding protein-1 and prolactin (PRL), two well-recognized markers of decidual cell maturation and a proteoglycan decorin (DCN). We reported that DCN restrains the human trophoblast renewal, migration, invasion and endovascular differentiation needed for uterine arterial remodeling during normal pregnancy. DCN overproduction by the decidua is associated with a hypo-invasive placenta and a serious pregnancy disorder, pre-eclampsia (PE). Furthermore, elevated maternal plasma DCN levels during the second trimester is a predictive biomarker of PE. While these paracrine roles of decidua-derived DCN on trophoblast physiology and pathology have been well-defined, it remains unknown whether DCN plays any autocrine role in decidual cell development. The objectives of this study were to examine the kinetics of DCN production during decidualization of human endometrial stromal cells; gestational age-related changes in DCN production by the first trimester decidua; and a possible autocrine role of DCN on decidual cell maturation. We found that DCN production is enhanced during decidualization of both primary and immortalized human endometrial stromal cells in vitro and during early gestation in decidual samples tested ex vivo, and that it is important for endometrial stromal cell maturation into a decidual phenotype. Decorin-depleted human endometrial stromal cells exposed to decidualizing stimuli failed to mature fully, as evidenced by fibroblastoid morphology, reduced insulin-like growth factor-binding protein-1 and PRL expression, and reduction in cellular ploidy. We identified heart and neural crest derivatives-expressed protein 2, and progesterone receptor as potential downstream mediators of DCN effects.The growth rate, representing the fitness of a bacterial population, is determined by the transcriptome. Chromosomal periodicity, which is known as the periodic spatial pattern of a preferred chromosomal distance in microbial genomes, is a representative overall feature of the transcriptome; however, whether and how it is associated with the bacterial growth rate are unknown. To address these questions, we analysed a total of 213 transcriptomes of multiple Escherichia coli strains growing in an assortment of culture conditions varying in terms of temperature, nutrition level and osmotic pressure. Intriguingly, Fourier transform analyses of the transcriptome identified a common chromosomal periodicity of transcriptomes, which was independent of the variation in genomes and environments. In addition, fitting of the data to a theoretical model, we found that the amplitudes of the periodic transcriptomes were significantly correlated with the growth rates. These results indicated that the amplitude of periodic transcriptomes is a parameter representing the global pattern of gene expression in correlation with the bacterial growth rate. Thus, our study provides a novel parameter for evaluating the adaptiveness of a growing bacterial population and quantitatively predicting the growth dynamics according to the global expression pattern.
Active surveillance (AS) for men with low-risk prostate cancer (PC) can lead to patient morbidity and healthcare overutilization. The aim of this study was to evaluate an AS-protocol using the Stockholm3 test and MRI to reduce biopsy intensity.

We conducted a prospective multicenter study of 280 invited men from a contemporary screening study (STHLM3), with Gleason Score (GS) 3 + 3 PC on a current AS-protocol. Patients underwent prostate-MRI and blood sampling for analysis of the Stockholm3 test including protein biomarkers, genetic variants and clinical variables to predict risk of GS ≥ 3 + 4 PC, then followed by systematic biopsies and targeted biopsies (for PIRADS ≥3 lesions) in all men. Primary outcomes were reclassification to GS ≥ 3 + 4 PC and clinically significant PC (csPC) including unfavorable intermediate risk PC or higher based on NCCN-guidelines.

Adding MRI-targeted biopsies to systematic biopsies increased sensitivity of GS ≥ 3 + 4 PC compared to systematic biopsies alone (relative sensitivity (RS) = 1.52; 95% CI = 1.28 to 1.85). Performing biopsies in only MRI positive increased sensitivity of GS ≥ 3 + 4 PC (RS = 1.30; 95% CI = 1.04 to 1.67), reduced number of biopsy procedures by 49.3% while missing 7.2% GS ≥ 3 + 4 PC and 1.4% csPCa. Excluding men with negative Stockholm3 test reduced number of MRI investigations at follow-up by 22.5%, biopsies by 56.8% while missing 6.9% GS ≥ 3 + 4 PC and 1.3% csPCa.

During AS, including MRI and targeted/systematic biopsies increase sensitivity of PC reclassification. Incorporation of risk prediction models including biomarkers may reduce the need for MRI use in men with low risk PC.
During AS, including MRI and targeted/systematic biopsies increase sensitivity of PC reclassification. Incorporation of risk prediction models including biomarkers may reduce the need for MRI use in men with low risk PC.
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition of immune dysregulation. Children often suffer from primary genetic forms of HLH, which can be triggered by infection. Others suffer from secondary HLH as a complication of infection, malignancy, or rheumatologic disease. Identifying the exact cause of HLH is crucial, as definitive treatment for primary disease is hematopoietic stem cell transplant. Adenoviruses have been associated with HLH but molecular epidemiology data are lacking.

We describe the clinical and virologic characteristics of 5 children admitted with adenovirus infection during 2018-2019 who developed HLH or HLH-like illness. Detailed virologic studies, including virus isolation and comprehensive molecular typing were performed.

All patients recovered; clinical management varied but included immunomodulating and antiviral therapies. A genetic predisposition for HLH was not identified in any patient. Adenovirus isolates were recovered from 4/5 cases; all were identipredisposition to HLH. These findings suggest that adenovirus 7 infection alone can result in HLH.
Opioid misuse in the USA is an epidemic. Utilization of neuromodulation for refractory chronic pain may reduce opioid-related morbidity and mortality, and associated economic costs.

To assess the impact of spinal cord stimulation (SCS) on opioid dose reduction.

The IBM MarketScan® database was retrospectively queried for all US patients with a chronic pain diagnosis undergoing SCS between 2010 and 2015. Opioid usage before and after the procedure was quantified as morphine milligram equivalents (MME).

A total of 8497 adult patients undergoing SCS were included. Within 1 yr of the procedure, 60.4% had some reduction in their opioid use, 34.2% moved to a clinically important lower dosage group, and 17.0% weaned off opioids entirely. The proportion of patients who completely weaned off opioids increased with decreasing preprocedure dose, ranging from 5.1% in the >90MME group to 34.2% in the ≤20 MME group. The following variables were associated with reduced odds of weaning off opioids post procedure long-term opioid use (odds ratio [OR] 0.26; 95% CI 0.21-0.30; P<.001), use of other pain medications (OR 0.75; 95% CI 0.65-0.87; P<.001), and obesity (OR 0.75; 95% CI 0.60-0.94; P=.01).

Patients undergoing SCS were able to reduce opioid usage. Given the potential to reduce the risks of long-term opioid therapy, this study lays the groundwork for efforts that may ultimately push stakeholders to reduce payment and policy barriers to SCS as part of an evidence-based, patient-centered approach to nonopioid solutions for chronic pain.
Patients undergoing SCS were able to reduce opioid usage. Given the potential to reduce the risks of long-term opioid therapy, this study lays the groundwork for efforts that may ultimately push stakeholders to reduce payment and policy barriers to SCS as part of an evidence-based, patient-centered approach to nonopioid solutions for chronic pain.
Cerebral complications in preeclampsia are leading causes of maternal mortality worldwide but pathophysiology is largely unknown and a challenge to study. Using an in vitro model of the human blood-brain barrier (BBB), we explored the role of vascular endothelial growth factor receptor 2 (VEGFR2) in preeclampsia.

The human brain endothelial cell line (hCMEC/D3) cultured on Tranwells insert was exposed (12 hours) to plasma from women with preeclampsia (n = 28), normal pregnancy (n = 28), and nonpregnant (n = 16) controls. Transendothelial electrical resistance (TEER) and permeability to 70 kDa fluorescein isothiocyanate (FITC)-dextran were measured for the assessment of BBB integrity. We explored possible underlying mechanisms, with a focus on the expression of tight junction proteins and phosphorylation of 2 tyrosine residues of VEGFR2, associated with vascular permeability and migration (pY951) and cell proliferation (pY1175). Plasma concentrations of soluble FMS-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) were also measured.

hCMEC/D3 exposed to plasma from women with preeclampsia exhibited reduced TEER and increased permeability to 70 kDa FITC-dextran. These cells upregulated the messenger ribonucleic acid (mRNA) levels of VEGFR2, and pY951-VEGFR2, but reduced pY1175-VEGFR2 (P < 0.05 in all cases). No difference in mRNA expression of tight junction protein was observed between groups. There was no correlation between angiogenic biomarkers and BBB permeability.

We present a promising in vitro model of the BBB in preeclampsia. Selective tyrosine phosphorylation of VEGFR2 may participate in the increased BBB permeability in preeclampsia irrespective of plasma concentrations of angiogenic biomarkers.
We present a promising in vitro model of the BBB in preeclampsia. Selective tyrosine phosphorylation of VEGFR2 may participate in the increased BBB permeability in preeclampsia irrespective of plasma concentrations of angiogenic biomarkers.Female germ cell development is a highly complex process that includes meiosis initiation, oocyte growth recruitment, oocyte meiosis retardation and resumption and final meiotic maturation. A series of coordinated molecular signaling factors ensure successful oogenesis. The recent rapid development of high-throughput sequencing technologies allows for the dynamic omics in female germ cells, which is essential for further understanding the regulatory mechanisms of molecular events comprehensively. In this review, we summarize the current literature of multi-omics sequenced by epigenome-, transcriptome- and proteome-associated technologies, which provide valuable information for understanding the regulation of key events during female germ cell development.Healthcare-Associated Infections (HAIs) are a major public health problem as they pose a serious risk for patients and providers, increasing morbidity, mortality, and length of stay as well as costs to patients and the health system. Prevention and control of HAIs has, therefore, become a priority for most healthcare systems. Systems simulation models have provided insights into the dynamics of HAIs and help to evaluate the effect of infection control interventions. However, as each systems simulation modeling method has strengths and limitations, combining these methods in hybrid models can offer a better tool to gain complementary views on, and deeper insights into, HAIs. Hybrid models can, therefore, assist decision-making at different levels of management, and provide a balance between simulation performance and result accuracy. This paper discusses these benefits in more depth but also highlights some challenges associated with the use of hybrid simulation models for modeling HAIs.A diagnostic of hypertension increases the risk of erectile dysfunction (ED); likewise, ED can be an early sign of hypertension. In both cases, there is evidence that endothelial dysfunction is a common link between the two conditions. During hypertension, the sustained and widespread release of pro-contractile factors (e.g., angiotensin II, endothelin 1, aldosterone) impairs the balance between vasoconstrictors and vasodilators and, in turn, detrimentally impacts vascular and erectile structures. This pro-hypertensive state associates with an enhancement in the generation of reactive oxygen species, which is not compensated by internal antioxidant mechanisms. Recently, the innate immune system, mainly via Toll-like receptor 4, has also been shown to actively contribute to the pathophysiology of hypertension and ED not only by inducing oxidative stress but also by sustaining a low-grade inflammatory state. Furthermore, some drugs used to treat hypertension can cause ED and, consequently, reduce compliance with the prescribed pharmacotherapy. To break down these challenges, in this review, we focus on discussing the well-established as well as the emerging mechanisms linking hypertension and ED with an emphasis on the signaling network of the vasculature and corpora cavernosa, the vascular-like structure of the penis.
Following a meropenem shortage, we implemented a post-prescription review with feedback (PPRF) in November 2015 with mandatory infectious disease (ID) consultation for all meropenem and imipenem courses > 72 hours. Providers were made aware of the policy via an electronic alert at the time of ordering.

A retrospective study was conducted at the University of Washington Medical Center (UWMC) and Harborview Medical Center (HMC) to evaluate the impact of the policy on antimicrobial consumption and clinical outcomes pre- and post-intervention during a 6-year period. Antimicrobial use was tracked using days of therapy (DOT) per 1,000 patient-days, and data were analyzed by an interrupted time series.

There were 4,066 and 2,552 patients in the pre- and post-intervention periods, respectively. Meropenem and imipenem use remained steady until the intervention, when a marked reduction in DOT/1,000 patient-days occurred at both hospitals (UWMC percentage change -72.1%, (95% CI -76.6, -66.9), P & 0.001; HMC percentage change -43.6%, (95% CI -59.9, -20.7), P = 0.001). Notably, although the intervention did not address antibiotic use until 72 hours after initiation, there was a significant decline in meropenem and imipenem initiation ("first starts") in the post-intervention period, with a 64.9% reduction (95% CI 58.7, 70.2; P &0.001) at UWMC and 44.7% reduction (95% CI 28.1, 57.4; P & 0.001) at HMC.

Mandatory ID consultation and PPRF for meropenem and imipenem beyond 72 hours resulted in a significant and sustained reduction in the use of these antibiotics and notably impacted their up-front usage.
Mandatory ID consultation and PPRF for meropenem and imipenem beyond 72 hours resulted in a significant and sustained reduction in the use of these antibiotics and notably impacted their up-front usage.
The Flavivirus genus includes several important pathogens such as Zika, dengue and yellow fever virus. Flavivirus RNA genomes contain a number of functionally important structures in their 3' untranslated regions (3'UTRs). Due to the diversity of sequences and topologies of these structures, their identification is often difficult. On the other hand, predictions of such structures is important for understanding of flavivirus replication cycles and development of antiviral strategies.

We have developed an algorithm for structured pattern search in RNA sequences, including secondary structures, pseudoknots and triple base interactions. Using the data on known conserved flavivirus 3'UTR structures, we constructed structural descriptors which covered the diversity of patterns in these motifs. The descriptors and the search algorithm were used for the construction of a database of flavivirus 3'UTR structures. Validating this approach, we identified a number of domains matching a general pattern of exoribonuclease Xrn1 - resistant RNAs in the growing group of insect-specific flaviviruses.

The Leiden Flavivirus RNA Structure Database is available at https//rna.liacs.nl. The search algorithm is available at https//github.com/LeidenRNA/SRHS.
The Leiden Flavivirus RNA Structure Database is available at https//rna.liacs.nl. The search algorithm is available at https//github.com/LeidenRNA/SRHS.
The 3D structure of chromatin in the nucleus is important for gene expression and regulation. Chromosome conformation capture techniques, such as Hi-C, generate large amounts of data showing interaction points on the genome but these are hard to interpret using standard tools.

We have developed CSynth, an interactive 3D genome browser and real-time chromatin restraint-based modeller to visualise models of any chromosome conformation capture (3C) data. Unlike other modelling systems CSynth allows dynamic interaction with the modelling parameters to allow experimentation and effects on the model. It also allows comparison of models generated from data in different tissues / cell states and the results of third-party 3D modelling outputs. In addition, we include an option to view and manipulate these complicated structures using Virtual Reality (VR) so scientists can immerse themselves in the models for further understanding. This VR component has also proven to be a valuable teaching and public engagement tool.

CSynth is web based and available to use at https//csynth.org.

Supplementary data are available at Bioinformatics online.
Supplementary data are available at Bioinformatics online.
Residency applications via virtual-interview could potentially mitigate the extensive cost and time required for customary in-person interviews. We outline the perception of medical students and residents on the use of virtual-interview for residency applications in lieu of in-person interviews.

We obtained 1824 responses from medical students and residents through an online questionnaire between March2019-Feb2020 in Texas-United States. The survey had 11 statements (five in favor of in-person interviews and 6 in favor of virtual interviews) that respondents could rank on a 5-point Likert scale. All statements' scores were summed based on the response given by each participant to create a total score between 11 and 55. The perception of the two groups was analyzed using an independent sample T-test and ANOVA.

We received a total of 1711 responses from medical students and 113 from medical residents. Respondents were more female (82.2% of medical students and 47.8% of residents), with a mean age of 22.87ward virtual-interviews to improve the interview process in the United States.
Hypotension following endotracheal intubation in the ICU is associated with poor outcomes. There is no formal prediction tool to help estimate the onset of this hemodynamic compromise. Our objective was to derive and validate a prediction model for immediate hypotension following endotracheal intubation.

A multicenter, prospective, cohort study enrolling 934 adults who underwent endotracheal intubation across 16 medical/surgical ICUs in the United States from July 2015-January 2017 was conducted to derive and validate a prediction model for immediate hypotension following endotracheal intubation. We defined hypotension as 1) mean arterial pressure <65 mmHg; 2) systolic blood pressure <80 mmHg and/or decrease in systolic blood pressure of 40% from baseline; 3) or the initiation or increase in any vasopressor in the 30 minutes following endotracheal intubation.

Post-intubation hypotension developed in 344 (36.8%) patients. In the full cohort, 11 variables were independently associated with hypotensiion with accuracy in both unstable and stable critically ill patients.

Clinicaltrials.gov identifier NCT02508948 and Registered Report Identifier RR2-10.2196/11101.
Clinicaltrials.gov identifier NCT02508948 and Registered Report Identifier RR2-10.2196/11101.Small RNA viruses only have a very limited coding capacity, thus most viral proteins have evolved to fulfill multiple functions. The highly conserved matrix protein 1 (M1) of influenza A viruses is a prime example for such a multifunctional protein, as it acts as a master regulator of virus replication whose different functions have to be tightly regulated. The underlying mechanisms, however, are still incompletely understood. Increasing evidence points towards an involvement of posttranslational modifications in the spatio-temporal regulation of M1 functions. Here, we analyzed the role of M1 tyrosine phosphorylation in genuine infection by using recombinant viruses expressing M1 phosphomutants. Presence of M1 Y132A led to significantly decreased viral replication compared to wildtype and M1 Y10F. Characterization of phosphorylation dynamics by mass spectrometry revealed the presence of Y132 phosphorylation in M1 incorporated into virions that is most likely mediated by membrane-associated Janus kinases late upon infection. Molecular dynamics simulations unraveled a potential phosphorylation-induced exposure of the positively charged linker domain between helices 4 and 5, supposably acting as interaction platform during viral assembly. Consistently, M1 Y132A showed a defect in lipid raft localization due to reduced interaction with viral HA protein resulting in a diminished structural stability of viral progeny and the formation of filamentous particles. Importantly, reduced M1-RNA binding affinity resulted in an inefficient viral genome incorporation and the production of non-infectious virions that interferes with virus pathogenicity in mice. This study advances our understanding of the importance of dynamic phosphorylation as a so far underestimated level of regulation of multifunctional viral proteins and emphasizes the potential feasibility of targeting posttranslational modifications of M1 as a novel antiviral intervention.The performances of the ImmuView Streptococcus pneumoniae (Sp) and Legionella pneumophila (Lp) urinary antigen test were compared to that of the BinaxNOW Sp and Lp assays, using frozen urine from 166 patients with Legionnaires' disease (LD) and 59 patients with pneumococcal pneumonia. Thirty Sp-positive or contrived cerebrospinal fluids (CSF) were also tested. Test specimens were collected and tested at different sites, with each site testing unique specimens by technologists blinded to expected results. No significant differences in test concordances were detected for the ImmuView and BinaxNOW assays for the Sp or Lp targets for urine from patients with pneumococcal pneumonia or LD when performance from both sites were combined. At one of two test sites the ImmuView Lp assay was more sensitive than the BinaxNOW assay, with no correlation between test performance and Lp serogroup 1 monoclonal type. Urines from six of seven patients with LD caused by Legionella spp. bacteria other than Lp serogroup 1 were negative in both assays. Both tests had equivalent performance for Sp-positive CSF. The clinical sensitivities for pneumococcal pneumonia were 88.1 and 94.4% for the ImmuView and Binax assays, and 87.6 and 84.2% for the Lp assays, respectively. Test specificities for pneumococcal pneumonia were 96.2 and 97.0% for the ImmuView and Binax assays, and 99.6 and 99.1% for the Lp assays. Both assays were highly specific for Sp in pediatric urines from children with nasopharyngeal colonization by the bacterium. ImmuView and BinaxNOW assay performance was equivalent in these studies.Validation of heart rate responses in wearable technology devices is generally composed of laboratory-based protocols that are steady state in nature and as a result, high accuracy measures are returned. However, there is a need to understand device validity in applied settings that include varied intensities of exercise. The purpose was to determine concurrent heart rate validity during trail running. Twenty-one healthy participants volunteered (female n = 10, [mean (SD)] age = 31 [11] years, height = 173.0 [7] cm, mass = 75.6 [13] kg). Participants were outfitted with wearable technology devices (Garmin Fenix 5 wristwatch, Jabra Elite Sport earbuds, Motiv ring, Scosche Rhythm+ forearm band, Suunto Spartan Sport watch with accompanying chest strap) and completed a self-paced 3.22 km trail run while concurrently wearing a criterion heart rate strap (Polar H7 heart rate monitor). The trail runs were out-and-back with the first 1.61 km in an uphill direction, and the 1.61 return being downhill in nature. Validity was determined through three methods Mean Absolute Percent Error (MAPE), Bland-Altman Limits of Agreement (LOA), and Lin's Concordance Coefficient (rC). Validity measures overall are as follows Garmin Fenix 5 (MAPE = 13%, LOA = -32 to 162, rC = 0.32), Jabra Elite Sport (MAPE = 23%, LOA = -464 to 503, rC = 0.38), Motiv ring (MAPE = 16%, LOA = -52 to 96, rC = 0.29), Scosche Rhythm+ (MAPE = 6%, LOA = -114 to 120, rC = 0.79), Suunto Spartan Sport (MAPE = 2%, LOA = -62 to 61, rC = 0.96). All photoplethysmography-based (PPG) devices displayed poor heart rate agreement during variable intensity trail running. Until technological advances occur in PPG-based devices allowing for acceptable agreement, heart rate in outdoor environments should be obtained using an ECG-based chest strap that can be connected to a wristwatch or other comparable receiver.The term "retroactive avoidance" refers to a special class of effects of future stimulus presentations on past behavioral responses. Specifically, it refers to the anticipatory avoidance of aversive stimuli that were unpredictable through random selection after the response. This phenomenon is supposed to challenge the common view of the arrow of time and the direction of causality. Preliminary evidence of "retroactive avoidance" has been published in mainstream psychological journals and started a heated debate about the robustness and the true existence of this effect. A series of seven experiments published in 2014 in the Journal of Consciousness Studies (Maier et al., 2014) tested the influence of randomly drawn future negative picture presentations on avoidance responses based on key presses preceding them. The final study in that series used a sophisticated quantum-based random stimulus selection procedure and implemented the most severe test of retroactive avoidance within this series. Evidence for the effect, though significant, was meager and anecdotal, Bayes factor (BF10) = 2. The research presented here represents an attempt to exactly replicate the original effect with a high-power (N = 2004) preregistered multi-lab study. The results indicate that the data favored the null effect (i.e., absence of retroactive avoidance) with a BF01 = 4.38. Given the empirical strengths of the study, namely its preregistration, multi-lab approach, high power, and Bayesian analysis used, this failed replication questions the validity and robustness of the original findings. Not reaching a decisive level of Bayesian evidence and not including skeptical researchers may be considered limitations of this study. Exploratory analyses of the change in evidence for the effect across time, performed on a post-hoc basis, revealed several potentially interesting anomalies in the data that might guide future research in this area.The tick-borne apicomplexan parasite, Babesia bovis, a highly persistent bovine pathogen, expresses VESA1 proteins on the infected erythrocyte surface to mediate cytoadhesion. The cytoadhesion ligand, VESA1, which protects the parasite from splenic passage, is itself protected from a host immune response by rapid antigenic variation. B. bovis relies upon segmental gene conversion (SGC) as a major mechanism to vary VESA1 structure. Gene conversion has been considered a form of homologous recombination (HR), a process for which Rad51 proteins are considered pivotal components. This could make BbRad51 a choice target for development of inhibitors that both interfere with parasite genome integrity and disrupt HR-dependent antigenic variation. Previously, we knocked out the Bbrad51 gene from the B. bovis haploid genome, resulting in a phenotype of sensitivity to methylmethane sulfonate (MMS) and apparent loss of HR-dependent integration of exogenous DNA. In a further characterization of BbRad51, we demonstrate herkely enzymatic mechanism(s) underlying SGC and suggest the existence of additional targets for development of small molecule inhibitors.
Of all cancer types, healthcare for lung cancer is the third most costly in Australia, but there is little detailed information about these costs. Our aim was to provide detailed population-based estimates of health system costs for lung cancer care, as a benchmark prior to wider availability of targeted therapies/immunotherapy and to inform cost-effectiveness analyses of lung cancer screening and other interventions in Australia.

Health system costs were estimated for incident lung cancers in the Australian 45 and Up Study cohort, diagnosed between recruitment (2006-2009) and 2013. Costs to June 2016 included services reimbursed via the Medicare Benefits Schedule, medicines reimbursed via the Pharmaceutical Benefits Scheme, inpatient hospitalisations, and emergency department presentations. Costs for cases and matched, cancer-free controls were compared to derive excess costs of care. Costs were disaggregated by patient and tumour characteristics. Data for more recent cases identified in hospital recordsprovides a framework for evaluating the health/economic impact of introducing lung cancer screening and other interventions in Australia.
Lung cancer healthcare costs are strongly associated with survival-related factors. Costs appeared stable over the period 2006-2013. This study provides a framework for evaluating the health/economic impact of introducing lung cancer screening and other interventions in Australia.Anthrax is a major zoonotic disease of wildlife, and in places like West Africa, it can be caused by Bacillus anthracis in arid nonsylvatic savannahs, and by B. cereus biovar anthracis (Bcbva) in sylvatic rainforests. Bcbva-caused anthrax has been implicated in as much as 38% of mortality in rainforest ecosystems, where insects can enhance the transmission of anthrax-causing bacteria. While anthrax is well-characterized in mammals, its transmission by insects points to an unidentified anthrax-resistance mechanism in its vectors. In mammals, a secreted anthrax toxin component, 83 kDa Protective Antigen (PA83), binds to cell-surface receptors and is cleaved by furin into an evolutionary-conserved PA20 and a pore-forming PA63 subunits. We show that PA20 increases the resistance of Drosophila flies and Culex mosquitoes to bacterial challenges, without directly affecting the bacterial growth. We further show that the PA83 loop known to be cleaved by furin to release PA20 from PA63 is, in part, responsible for the PA20-mediated protection. We found that PA20 binds directly to the Toll activating peptidoglycan-recognition protein-SA (PGRP-SA) and that the Toll/NF-κB pathway is necessary for the PA20-mediated protection of infected flies. This effect of PA20 on innate immunity may also exist in mammals we show that PA20 binds to human PGRP-SA ortholog. Moreover, the constitutive activity of Imd/NF-κB pathway in MAPKK Dsor1 mutant flies is sufficient to confer the protection from bacterial infections in a manner that is independent of PA20 treatment. Lastly, Clostridium septicum alpha toxin protects flies from anthrax-causing bacteria, showing that other pathogens may help insects resist anthrax. The mechanism of anthrax resistance in insects has direct implications on insect-mediated anthrax transmission for wildlife management, and with potential for applications, such as reducing the sensitivity of pollinating insects to bacterial pathogens.The San Francisco Bay outflow creates a tidally influenced low-salinity plume that affects adjacent coastal sites. In the study region, Anthopleura elegantissima (Cnidaria; Anthozoa) hosts a single symbiont, the dinoflagellate Breviolum muscatinei. Salinity, temperature, and aerial stress induce a bleaching response similar to corals where symbionts are expelled, causing further energetic stress. Using field observations of environmental conditions and symbiont abundance at sites on a gradient of exposure to estuarine outflow, along with a fully crossed multifactorial lab experiment, we tested for changes in symbiont abundance in response to various combinations of three stressors. Lab experiments were designed to mimic short term outflow events with low salinity, high temperature, and aerial exposure treatments. The lab aerial exposure treatment was a statistically significant factor in suppressing symbiont repopulation (ANOVA, p = .017). In the field, symbiont density decreased with increasing tidal height at the site closest to freshwater outflow (ANOVA, p = .007), suggesting that aerial exposure may affect symbiont density more than sea surface temperature and salinity. Unanticipated documentation of survival in 9 months of sand burial and subsequent repopulation of symbionts is reported as a six-month extension to past observations, exemplifying strong tolerance to environmental insult in this Cnidarian mutualism. The study of this symbiosis is useful in examining predicted changes in ocean conditions in tidepool communities and considering relative sources of stress.Modified vaccinia virus Ankara (MVA) is an approved smallpox vaccine and a promising vaccine vector for other pathogens as well as for cancer therapeutics with more than 200 current or completed clinical trials. MVA was derived by passaging the parental Ankara vaccine virus hundreds of times in chick embryo fibroblasts during which it lost the ability to replicate in human and most other mammalian cells. Although this replication deficiency is an important safety feature, the genetic basis of the host restriction is not understood. Here, an unbiased human genome-wide RNAi screen in human A549 cells revealed that the zinc-finger antiviral protein (ZAP), previously shown to inhibit certain RNA viruses, is a host restriction factor for MVA, a DNA virus. Additional studies demonstrated enhanced MVA replication in several human cell lines following knockdown of ZAP. Furthermore, CRISPR-Cas9 knockout of ZAP in human A549 cells increased MVA replication and spread by more than one log but had no effect on a non-attenuated strain of vaccinia virus. The intact viral C16 protein, which had been disrupted in MVA, antagonized ZAP by binding and sequestering the protein in cytoplasmic punctate structures. Studies aimed at exploring the mechanism by which ZAP restricts MVA replication in the absence of C16 showed that knockout of ZAP had no discernible effect on viral DNA or individual mRNA or protein species as determined by droplet digital polymerase chain reaction, deep RNA sequencing and mass spectrometry, respectively. Instead, inactivation of ZAP reduced the number of aberrant, dense, spherical particles that typically form in MVA-infected human cells, suggesting that ZAP has a novel role in interfering with a late step in the assembly of infectious MVA virions in the absence of the C16 protein.In this study, we performed an analysis of the impact of performance enhancing polymorphisms (PEPs) on gymnastic aptitude while considering epistatic effects. Seven PEPs (rs1815739, rs8192678, rs4253778, rs6265, rs5443, rs1076560, rs362584) were considered in a case (gymnasts)-control (sedentary individuals) setting. The study sample comprised of two athletes' sets 27 elite (aged 24.8 ± 2.1 years) and 46 sub-elite (aged 19.7 ± 2.4 years) sportsmen as well as a control group of 245 sedentary individuals (aged 22.5 ± 2.1 years). The DNA was derived from saliva and PEP alleles were determined by PCR, RT-PCR. Following Multifactor Dimensionality Reduction, logistic regression models were built. The synergistic effect for rs1815739 x rs362584 reached 5.43%. The rs1815739 x rs362584 epistatic regression model exhibited a good fit to the data (Chi-squared = 33.758, p ≈ 0) achieving a significant improvement in sportsmen identification over naïve guessing. The area under the receiver operating characteristic curve was 0.715 (Z-score = 38.917, p ≈ 0). In contrast, the additive ACTN3 -SNAP-25 logistic regression model has been verified as non-significant. We demonstrate that a gene involved in the differentiation of muscle architecture-ACTN3 and a gene, which plays an important role in the nervous system-SNAP-25 interact. From the perspective originally established by the Berlin Academy of Science in 1751, the matter of communication between the brain and muscles via nerves adopts molecular manifestations. Further in-vitro investigations are required to explain the molecular details of the rs1815739 -rs362584 interaction.
A sufficient screening rate is indispensable to optimize the positive impact of colorectal cancer (CRC) screening. This study aimed to evaluate the effect of an additional outreach of providing an opportunity to obtain a kit for fecal immunochemical test (FIT) during the general health check-up to increase CRC screening rate.

This was a longitudinal study using pre-existing data in Kujukuri Town, Japan. The town provided CRC screening in the fiscal year (FY) 2017 using an existing procedure for all beneficiaries of the National Health Insurance, whereas in FY 2018, an additional outreach effort was made to only those with an even number of age (exposed group), who were offered an opportunity to obtain a kit for FIT at the time of general health check-ups but not to those with an odd number of age (control group). To estimate the effectiveness, generalized estimating equation (GEE) with individuals as clusters was performed.

In total, 3,530 individuals were included (1,708 in the control group and 1,822 in the exposed group). GEE showed significant interaction between the groups (control and exposed) and FYs (2017 and 2018) (p<0.001), indicating that the change in CRC screening rate from 2017 to 2018 was significantly different between the two groups. Although an achieved actual rate of 17.1% in the exposed group in FY 2018 was low, the additional outreach increased the rate by 5.8 percentage point (95% confidence interval, 3.5-8.1) compared with an existing rate.

Additional outreach of providing an opportunity to obtain a kit for FIT at the time of the general health check-up improved the CRC screening rate. However, screening rate achieved by this strategy remained low, indicating further efforts is required.
Additional outreach of providing an opportunity to obtain a kit for FIT at the time of the general health check-up improved the CRC screening rate. However, screening rate achieved by this strategy remained low, indicating further efforts is required.The induction of broad and potent immunity by vaccines is the key focus of research efforts aimed at protecting against HIV-1 infection. Soluble native-like HIV-1 envelope glycoproteins have shown promise as vaccine candidates as they can induce potent autologous neutralizing responses in rabbits and non-human primates. In this study, monoclonal antibodies were isolated and characterized from rhesus macaques immunized with the BG505 SOSIP.664 trimer to better understand vaccine-induced antibody responses. Our studies reveal a diverse landscape of antibodies recognizing immunodominant strain-specific epitopes and non-neutralizing neo-epitopes. Additionally, we isolated a subset of mAbs against an epitope cluster at the gp120-gp41 interface that recognize the highly conserved fusion peptide and the glycan at position 88 and have characteristics akin to several human-derived broadly neutralizing antibodies.The conservation status of several pelagic shark species is considered vulnerable with declining populations, yet data on shark fishing mortality remain limited for large ocean regions. Pelagic sharks are increasingly retained by mixed-species fisheries, or are discarded and not reported by selective fisheries for tunas (Thunnus spp.) or swordfish (Xiphias gladius). We estimated the fishing mortality of sharks (landings plus discard mortalities) in a South African-flagged pelagic longline fishery with diverse targeting and discard behaviour. A hierarchical cluster analysis was used to stratify the fleet according to the relative proportions of tunas, swordfish, blue sharks (Prionace glauca) and shortfin mako sharks (Isurus oxyrinchus) landed by individual vessels between 2013 and 2015. A spatial analysis of logbook data indicated that subfleets operated in distinct fishing areas, with overlap. Approximately 5% of all commercial longlines set during 2015 were sampled by a fisheries-independent observer, and thvels of observer sampling are required to increase confidence in discard ratio estimates.Isokinetic dynamometry is the gold standard for testing maximal strength in elite sport and rehabilitation settings. To be clinically useful, such tests should be valid and reliable. Despite some evidence regarding the relative test vs retest reliability of knee dynamometry, there is still a paucity of research regarding the absolute reliability parameters. The purpose of this study was to assess the absolute and relative intra-device reproducibility of isokinetic knee flexion and extension using the novel SMM iMoment dynamometer. A total of 19 participants (13 males and 6 females, aged 24 (2) years, height 178 (9) cm and weight 76 (11) kg) performed two identical knee isokinetic tests with at least a week of rest between measurements. Peak torque of knee extension and flexion were determined at 60°/s. Moderate (0.892) to excellent (0.988) relative reliability using the intraclass correlation coefficient (ICC) was obtained for peak knee torque. Absolute reliability assessed with a standard error of measurement (SEM %) was low, ranging from 2.54% to 6.93%, whereas the smallest real difference (SRD %) was moderate, ranging from 7.04% to 19.22%. Furthermore, there were no significant correlations between means and differences of two measurements, and Bland-Altman plots also showed no signs of heteroscedasticity. Our measurement protocol established the moderate to excellent reliability of the novel SMM iMoment isokinetic dynamometer. Therefore, this dynamometer can be applied in sport rehabilitation settings to measure maximal knee strength.Shigella flexneri invades host cells by entering within a bacteria-containing vacuole (BCV). In order to establish its niche in the host cytosol, the bacterium ruptures its BCV. Contacts between S. flexneri BCV and infection-associated macropinosomes (IAMs) formed in situ have been reported to enhance BCV disintegration. The mechanism underlying S. flexneri vacuolar escape remains however obscure. To decipher the molecular mechanism priming the communication between the IAMs and S. flexneri BCV, we performed mass spectrometry-based analysis of the magnetically purified IAMs from S. flexneri-infected cells. While proteins involved in host recycling and exocytic pathways were significantly enriched at the IAMs, we demonstrate more precisely that the S. flexneri type III effector protein IpgD mediates the recruitment of the exocyst to the IAMs through the Rab8/Rab11 pathway. This recruitment results in IAM clustering around S. flexneri BCV. More importantly, we reveal that IAM clustering subsequently facilitates an IAM-mediated unwrapping of the ruptured vacuole membranes from S. flexneri, enabling the naked bacterium to be ready for intercellular spread via actin-based motility. Taken together, our work untangles the molecular cascade of S. flexneri-driven host trafficking subversion at IAMs to develop its cytosolic lifestyle, a crucial step en route for infection progression at cellular and tissue level.
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