Overgaardsun1271

Apolipoprotein A-I mimetic peptide stops illness by simply growing tetrahydrobiopterin by way of damaging GTP-cyclohydrolase One particular and decreasing uncoupled endothelial n . o . synthase action.

Results of Filling as well as Perimeter Problems on the Overall performance associated with Sonography Compressional Viscoelastography: A Computational Simulator Study to help Fresh Design.

Utilization of signal detection methods in longitudinal claims data can improve post-marketing drug surveillance, but to date there has been limited application. The aim of this study is to use 3 approaches, the proportional reporting ratio, Gamma Poisson Shrinker, and tree-based scan statistic in detecting adverse drug events (ADEs) attributed to trastuzumab using an administrative claims dataset.

Using data from the Texas Cancer Registry and SEER linked to Medicare from 2010 to 2013, we conducted 12 propensity score matching. Breast cancer HER2+ patients treated with trastuzumab in addition to standard chemotherapy were matched to HER2- patients treated with standard chemotherapy. Inpatient and outpatient encounters up to 6 months from start of therapy were used to identify adverse events.

A total of 4191 patients were included in the study. Across all methods, use of trastuzumab generated signals on 9 distinct body systems. Cardiomyopathy and heart valve disease were the most consistently detected signals. Clinical review determined that most signals represented known ADEs.

We showed that claims data can be used to complement current ADE monitoring using common data mining methods with propensity score matching. Our analysis identified all expected ADEs associated with trastuzumab, and additional signals of valvular heart disorders.

We showed that claims data can be used to complement current ADE monitoring using common data mining methods with propensity score matching. Our analysis identified all expected ADEs associated with trastuzumab, and additional signals of valvular heart disorders.Land plants first evolved from freshwater algae, and flowering plants returned to water as early as the Cretaceous and multiple times subsequently. Alismatales is the largest clade of aquatic angiosperms including all marine angiosperms, as well as terrestrial plants. We used Alismatales to explore plant adaptations to aquatic environments by analyzing a data set that included 95 samples (89 Alismatales species) covering four genomes and 91 transcriptomes (59 generated in this study). To provide a basis for investigating adaptations, we assessed phylogenetic conflict and whole-genome duplication (WGD) events in Alismatales. We recovered a relationship for the three main clades in Alismatales as (Tofieldiaceae, Araceae) + core Alismatids. We also found phylogenetic conflict among the three main clades that was best explained by incomplete lineage sorting and introgression. Overall, we identified 18 putative WGD events across Alismatales. CDK inhibitor drugs One of them occurred at the most recent common ancestor of core Alismatids, and three occurred at seagrass lineages. We also found that lineage and life-form were both important for different evolutionary patterns for the genes related to freshwater and marine adaptation. link2 For example, several light- or ethylene-related genes were lost in the seagrass Zosteraceae, but are present in other seagrasses and freshwater species. Stomata-related genes were lost in both submersed freshwater species and seagrasses. Nicotianamine synthase genes, which are important in iron intake, expanded in both submersed freshwater species and seagrasses. Our results advance the understanding of the adaptation to aquatic environments and WGDs using phylogenomics.

Recent population-based data are limited regarding influenza-associated hospitalizations in U.S. children.

We identified children <18 years hospitalized with laboratory-confirmed influenza during 2010-2019 seasons through CDC's Influenza Hospitalization Surveillance Network. Adjusted hospitalization and in-hospital mortality rates were calculated, and multivariable logistic regression was conducted to evaluate risk factors for pneumonia, intensive care unit (ICU) admission, mechanical ventilation, and death.

Over 9 seasons, adjusted influenza-associated hospitalization incidence rates ranged from 10-375 per 100,000 persons each season and were highest among infants <6 months. Rates decreased with increasing age. The highest in-hospital mortality rates were observed in children <6 months (0.73 per 100,000 persons). Over time, antiviral treatment significantly increased from 56% to 85% (P < .001) and influenza vaccination rates increased from 33% to 44% (P = .003). Among the 13,235 hospitalized children, 2,676 (20%) of hospitalized children were admitted to the ICU, 2,262 (17%) had pneumonia, 690 (5%) required mechanical ventilation, and 72 (0.5%) died during hospitalization. link= CDK inhibitor drugs As compared with those <6 months of age, hospitalized children ≥13 years had higher odds of pneumonia (adjusted odds ratios [aOR], 2.7; 95% confidence interval [CI], 2.1-3.4), ICU admission (aOR, 1.6; 95% CI, 1.3-1.9), mechanical ventilation (aOR, 1.6; 95% CI, 1.1-2.2), and death (aOR, 3.3; 95% CI, 1.2-9.3).

Hospitalization and death rates were greatest in younger children at the population level. Among hospitalized children, however, older children had a higher risk of severe outcomes. Continued efforts to prevent and attenuate influenza in children are needed.

Hospitalization and death rates were greatest in younger children at the population level. Among hospitalized children, however, older children had a higher risk of severe outcomes. Continued efforts to prevent and attenuate influenza in children are needed.Abuse of androgens and erythropoietin has led to hormones being the most effective and frequent class of ergogenic substances prohibited in elite sports by the World Anti-Doping Agency (WADA). At present, thyroid hormone (TH) abuse is not prohibited, but its prevalence among elite athletes and nonprohibited status remains controversial. A corollary of prohibiting hormones for elite sports is that endocrinologists must be aware of a professional athlete's risk of disqualification for using prohibited hormones and/or to certify Therapeutic Use Exemptions, which allow individual athletes to use prohibited substances for valid medical indications. This narrative review considers the status of TH within the framework of the WADA Code criteria for prohibiting substances, which requires meeting 2 of 3 equally important criteria of potential performance enhancement, harmfulness to health, and violation of the spirit of sport. In considering the valid clinical uses of TH, the prevalence of TH use among young adults, the reason why some athletes seek to use TH, and the pathophysiology of sought-after and adverse effects of TH abuse, together with the challenges of detecting TH abuse, it can be concluded that, on the basis of present data, prohibition of TH in elite sport is neither justified nor feasible.

The epidemiology of orbital cellulitis likely has evolved due to the emergence of methicillin-resistant Staphylococcus aureus (MRSA) and the adoption of pneumococcal conjugate vaccination. In the absence of published guidelines, management is highly variable. We characterized epidemiology and management over an 11-year period.

A retrospective cohort study of children 0 to 21 years of age with orbital cellulitis +/- subperiosteal orbital abscess hospitalized at a large quaternary children's hospital from January 2008 to June 2018. We reviewed charts for demographic characteristics, clinical features, management, and outcomes. Using multivariable logistic regression, we evaluated predictors of surgical intervention and assessed whether corticosteroid use or antibiotic duration was related to clinical outcomes.

Among 220 patients, methicillin-susceptible S. aureus was the most common organism (26.3%), with MRSA found in only 5.0%. Rates of vancomycin use fluctuated annually from 40.9% to 84.6%. Surgery wasd ≤ 2 weeks of therapy, suggesting that shorter durations are adequate in some patients.

Patient exposure to antibiotics promotes the emergence of drug-resistant pathogens. The aim of this study was to identify whether the temporal dynamics of resistance emergence at the individual-patient level were predictable for specific pathogen-drug classes.

Following a systematic review, a novel robust error meta-regression (REMR) method for dose-response meta-analysis (DRMA) was used to estimate the odds ratio (OR) for carrying resistant bacteria during and following treatment compared to baseline. Probability density functions fitted to the resulting dose-response curves were then used to optimize the period during and/or after treatment when resistant pathogens were most likely to be identified.

Studies of Streptococcus pneumoniae treatment with β-lactam antibiotics demonstrated a peak in resistance prevalence among patients four days after completing treatment with a 3.32-fold increase in odds (95%CI 1.71 - 6.46). Resistance waned more gradually than it emerged, returning to pre-exposure levels one month after treatment (OR 0.98, 95%CI 0.55 - 1.75). Patient isolation during the peak dose-response period would be expected to reduce the risk that a transmitted pathogen is resistant equivalently to a 50% longer isolation window timed from the first day of treatment.

Predictable temporal dynamics of resistance levels have implications both for surveillance and control.

Predictable temporal dynamics of resistance levels have implications both for surveillance and control.Lineage-determining transcription factors (LD-TFs) drive the differentiation of progenitor cells into a specific lineage. In CD4+ T cells, T-bet dictates differentiation of the TH1 lineage, whereas GATA3 drives differentiation of the alternative TH2 lineage. However, LD-TFs, including T-bet and GATA3, are frequently co-expressed but how this affects LD-TF function is not known. By expressing T-bet and GATA3 separately or together in mouse T cells, we show that T-bet sequesters GATA3 at its target sites, thereby removing GATA3 from TH2 genes. This redistribution of GATA3 is independent of GATA3 DNA binding activity and is instead mediated by the T-bet DNA binding domain, which interacts with the GATA3 DNA binding domain and changes GATA3's sequence binding preference. This mechanism allows T-bet to drive the TH1 gene expression program in the presence of GATA3. We propose that redistribution of one LD-TF by another may be a common mechanism that could explain how specific cell fate choices can be made even in the presence of other transcription factors driving alternative differentiation pathways.

Given that COVID-19 and recent natural disasters exacerbated the shortage of medication for opioid use disorder (MOUD) services and were associated with increased opioid overdose mortality, it is important to examine how a community's ability to respond to natural disasters and infectious disease outbreaks is associated with MOUD access.

To examine the association of community vulnerability to disasters and pandemics with geographic access to each of the 3 MOUDs and whether this association differs by urban, suburban, or rural classification.

This cross-sectional study of zip code tabulation areas (ZCTAs) in the continental United States excluding Washington, DC, conducted a geospatial analysis of 2020 treatment location data.

Social vulnerability index (US Centers for Disease Control and Prevention measure of vulnerability to disasters or pandemics).

Drive time in minutes from the population-weighted center of the ZCTA to the ZCTA of the nearest treatment location for each treatment type (buprenorpst in suburban communities. Rural communities had poor geographic access regardless of vulnerability status. Future disaster preparedness planning should match the location of services to communities with greater vulnerability to prevent inequities in overdose deaths.

In this study, communities with greater vulnerability did not have greater geographic access to MOUD, and the mismatch between vulnerability and medication access was greatest in suburban communities. Rural communities had poor geographic access regardless of vulnerability status. Future disaster preparedness planning should match the location of services to communities with greater vulnerability to prevent inequities in overdose deaths.

Hypercholesterolemia, which is a cardiovascular risk factor, may also be associated with dementia risk. The benefit of statin treatment on dementia risk is controversial.

To determine whether individuals with familial hypercholesterolemia (FH), who have been exposed to lifelong hypercholesterolemia, have an excess risk of dementia and whether statin use is associated with dementia risk.

This was a prospective cohort study performed from 2008 to 2018 in Norway. Statistical analysis was performed from January 2021 to February 2022. This study included individuals with genetically verified FH and age-matched and sex-matched controls obtained from the general Norwegian population.

Dementia was defined according to International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes F00-03 and G30.

Incident cases of total dementia, vascular dementia, Alzheimer disease-dementia in Alzheimer disease, and data on lipid-lowering medication were obtained from the Norwegian Pa with FH vs matched controls (HR for total dementia, 0.9; 95% CI, 0.7-1.2). There was no association between cumulative DDDs of statins and total dementia in patients with FH with HRs of 1.2 (95% CI, 0.4-3.8) for cumulative DDDs of 5000 to 10 000 and 1.9 (95% CI, 0.7-5.0) for cumulative DDDs greater than 10 000.

These findings suggest that individuals with FH have no excess risk of dementia compared with age-matched and sex-matched controls and that there is no association between use of statins and risk of dementia in patients with FH.

These findings suggest that individuals with FH have no excess risk of dementia compared with age-matched and sex-matched controls and that there is no association between use of statins and risk of dementia in patients with FH.

Neurologic adverse events (NAEs) due to immune checkpoint inhibitors (ICIs) can be fatal but are underexplored.

To compare NAEs reported in randomized clinical trials (RCTs) of US Food and Drug Administration-approved ICIs with other forms of chemotherapy and placebo.

Bibliographic databases (Embase, Ovid, MEDLINE, and Scopus data) and trial registries (ClinicalTrials.gov) were searched from inception through March 1, 2020.

Phase II/III RCTs evaluating the use of ICIs were eligible for inclusion. Unpublished trials were excluded from the analysis.

Two investigators independently performed screening of trials using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. NAEs were recorded for each arm. Data were pooled using a random-effects model.

The risk of NAEs with ICI use compared with any drug regimen, cytotoxic chemotherapy, and placebo.

A total 39 trials including 23 705 patients were analyzed (16 135 [68.0%] men, 7866 [33.1%] White). The overall risk othe use of ICI. When compared with chemotherapy, the overall risk of NAE, peripheral neuropathy, paresthesia, and dysgeusia was lower with ICI use; however, when compared with placebo, the risk of NAEs is higher with the use of ICI.

Results of this meta-analysis suggest that the overall risk of NAEs, peripheral neuropathy, and dysgeusia is lower with the use of ICI. When compared with chemotherapy, the overall risk of NAE, peripheral neuropathy, paresthesia, and dysgeusia was lower with ICI use; however, when compared with placebo, the risk of NAEs is higher with the use of ICI.

SARS-CoV-2 entry requires the TMPRSS2 cell surface protease. link3 Antiandrogen therapies reduce expression of TMPRSS2.

To determine if temporary androgen suppression induced by degarelix improves clinical outcomes of inpatients hospitalized with COVID-19.

The Hormonal Intervention for the Treatment in Veterans With COVID-19 Requiring Hospitalization (HITCH) phase 2, placebo-controlled, double-blind, randomized clinical trial compared efficacy of degarelix plus standard care vs placebo plus standard care on clinical outcomes in men hospitalized with COVID-19 but not requiring invasive mechanical ventilation. Inpatients were enrolled at 14 Department of Veterans Affairs hospitals from July 22, 2020, to April 8, 2021. Data were analyzed from August 9 to October 15, 2021.

Patients stratified by age, history of hypertension, and disease severity were centrally randomized 21 to degarelix, (1-time subcutaneous dose of 240 mg) or a saline placebo. Standard care included but was not limited to supplemental oxygen, inicalTrials.gov Identifier NCT04397718.

ClinicalTrials.gov Identifier NCT04397718.

The US Food and Drug Administration (FDA)-approved indications can be factors in prescribing practices and insurance coverage, yet the frequency with which the extrapolation of clinical characteristics from pivotal trial data to the final approved indication occurs is not well understood.

To evaluate the frequency of extrapolation beyond pivotal trial data into approved indications in relation to disease severity, disease subtype, and concomitant medication use.

In a cross-sectional study, the characteristics of patients in pivotal trials of 105 novel drug approvals from 2015 to 2017 were identified and compared with the FDA-approved indications for the drugs. Main sources analyzed included FDA reviews, published material describing the pivotal trials, and the original drug labeling. The study was conducted from July 4, 2019, to June 1, 2021.

Clinical characteristics of pivotal trials used in FDA approval.

Main outcomes included the nature and frequency of extrapolation from study populations to theng to determine whether new safety issues arise, or effectiveness differs from expectations when these medications are used in broader real-world populations.

The findings of this study suggest that extrapolation from pivotal trial data to FDA-approved indications is common. Although extrapolations may be grounded in reasonable clinical predictions, they can limit the generalizability of such indications to specific prescribing decisions; these findings suggest a greater need for close postapproval monitoring to determine whether new safety issues arise, or effectiveness differs from expectations when these medications are used in broader real-world populations.

During the COVID-19 pandemic, urgent clinical management of patients has mainly included drugs currently administered for other diseases, referred to as repositioned drugs. As a result, some of these drugs have proved to be not only ineffective but also harmful because of adverse events associated with drug-drug interactions (DDIs).

To identify DDIs that led to adverse clinical outcomes and/or adverse drug reactions in patients with COVID-19 by systematically reviewing the literature and assessing the value of drug interaction checkers in identifying such events.

After identification of the drugs used during the COVID-19 pandemic, the drug interaction checkers Drugs.com, COVID-19 Drug Interactions, LexiComp, Medscape, and WebMD were consulted to analyze theoretical DDI-associated adverse events in patients with COVID-19 from March 1, 2020, through February 28, 2022. A systematic literature review was performed by searching the databases PubMed, Scopus, and Cochrane for articles published from March 1, 2tween the COVID-19 drugs and those already used by the patients should be evaluated.

The main finding of this systematic review is that the use of drug interaction checkers could have identified several DDI-associated adverse drug reactions, including severe and life-threatening events. Both the interactions between the drugs used to treat COVID-19 and between the COVID-19 drugs and those already used by the patients should be evaluated.We compared antibody and T-cell responses against the severe acute respiratory syndrome coronavirus 2 vaccine strain spike protein to responses against the Omicron variant in 15 messenger RNA vaccine recipients. While these individuals had significantly lower levels of antibodies that inhibited Omicron spike protein binding to ACE2, there was no difference in T-cell responses.

The efficacy of tocilizumab (TCZ) in the treatment of Takayasu arteritis (TA) was demonstrated in randomized controlled trials. The objective of this study was to analyze the effectiveness of combining TCZ with glucocorticoids (GC) as induction therapy in patients with TA.

This was a retrospective observational study including 32 patients with newly-diagnosed TA. Clinical effectiveness of TCZ in maintaining relapse-free remission and GC-tapering were compared between patients who were treated with TCZ plus GC and those who were treated with GC with or without immunosuppressants.

The study comprised 32 patients (27 women/5 men) with a median age of 25.5 years (range, 13-72). In the TCZ group (n = 14), patients received TCZ in combination with GC as an induction therapy. In the non-TCZ group (n = 18), patients were treated with single-agent GC or GC plus immunosuppressant. In the matched analysis, relapse-free survival rate was significantly higher in the TCZ group as compared to the non-TCZ group during GC taper.

TCZ, in combination with GC, would be an effective alternative induction regimen for patients with TA.

TCZ, in combination with GC, would be an effective alternative induction regimen for patients with TA.

A wide spectrum of mesenchymal tumors harboring ALK gene rearrangements has been identified outside the archetypal example of ALK-positive inflammatory myofibroblastic tumors.

To evaluate the molecular pathology of unusual ALK-positive mesenchymal tumors and their response to ALK-targeted treatments.

Seven patients with ALK-positive mesenchymal tumors, including inflammatory epithelioid cell sarcoma, undifferentiated sarcoma, histiocytic neoplasm, smooth muscle tumor of uncertain malignant potential (STUMP), and atypical fibrohistiocytic tumor, were included on the basis of aberrant ALK immunoexpression. Patients with inflammatory myofibroblastic tumors were excluded from the study. ALK gene rearrangement was investigated either by fluorescence in situ hybridization or next-generation sequencing.

ALK was immunolabeled in all patients, diffusely (≥50%) in 6 patients and partially (10%-50%) in 1 patient. ALK gene rearrangement was discovered in 5 of the 6 available patients. The 3'-partners of ALK fusioiagnosis and personalized treatment.Small molecule targeting of self-splicing RNAs like group I and II introns has been limited in part by the lack of a universal high-throughput screening platform for studies of splicing inhibition and kinetics. Here, we present the development of a molecular beacon assay for monitoring the accumulation of spliced exons during RNA splicing reactions. In this case, we applied it to the autocatalyzed reaction of the H.c.LSU group II intron found in the mitochondria of the pathogenic dimorphic fungus Histoplasma capsulatum. We find that a molecular beacon with the loop length of 18 nucleotides selectively recognizes ligated exons formed during self-splicing and exhibits high fluorescent signal upon binding of its target. We demonstrate that the fluorescent assay using molecular beacons can be successfully applied to kinetic characterization of the splicing reaction and determination of inhibition constants for small molecules. The results presented herein offer support for a molecular beacon approach to identifying small molecule inhibitors of intron splicing.Locomotion in different directions is vital for animal life and requires fine-adjusted neural activity of spinal networks. To compare the levels of recruitability of the locomotor circuitry responsible for forward and backward stepping, several electromyographic and kinematic characteristics of the two locomotor modes were analysed in decerebrated cats. Electrical epidural spinal cord stimulation was used to evoke forward and backward locomotion on a treadmill belt. The functional state of the bilateral spinal networks was tuned by symmetrical and asymmetrical epidural stimulation. A significant deficit in the backward but not forward stepping was observed when laterally shifted epidural stimulation was used but was not observed with central stimulation only half of the cats were able to perform bilateral stepping, but all the cats performed forward stepping. This difference was in accordance with the features of stepping during central epidural stimulation. Both the recruitability and stability of the EMG signals as well as inter-limb coordination during backward stepping were significantly decreased compared with those during forward stepping. The possible underlying neural mechanisms of the obtained functional differences of backward and forward locomotion (spinal network organisation, commissural communication and supraspinal influence) are discussed.

Currently known associations between common genetic variants and colorectal cancer explain less than half of its heritability of 25%. As alcohol consumption has a J-shape association with colorectal cancer risk, nondrinking and heavy drinking are both risk factors for colorectal cancer.

Individual-level data was pooled from the Colon Cancer Family Registry, Colorectal Transdisciplinary Study, and Genetics and Epidemiology of Colorectal Cancer Consortium to compare nondrinkers (≤1 g/day) and heavy drinkers (>28 g/day) with light-to-moderate drinkers (1-28 g/day) in GxE analyses. To improve power, we implemented joint 2df and 3df tests and a novel two-step method that modifies the weighted hypothesis testing framework. We prioritized putative causal variants by predicting allelic effects using support vector machine models.

For nondrinking as compared with light-to-moderate drinking, the hybrid two-step approach identified 13 significant SNPs with pairwise r2 > 0.9 in the 10q24.2/COX15 region. When stratified by alcohol intake, the A allele of lead SNP rs2300985 has a dose-response increase in risk of colorectal cancer as compared with the G allele in light-to-moderate drinkers [OR for GA genotype = 1.11; 95% confidence interval (CI), 1.06-1.17; OR for AA genotype = 1.22; 95% CI, 1.14-1.31], but not in nondrinkers or heavy drinkers. Among the correlated candidate SNPs in the 10q24.2/COX15 region, rs1318920 was predicted to disrupt an HNF4 transcription factor binding motif.

Our study suggests that the association with colorectal cancer in 10q24.2/COX15 observed in genome-wide association study is strongest in nondrinkers. We also identified rs1318920 as the putative causal regulatory variant for the region.

The study identifies multifaceted evidence of a possible functional effect for rs1318920.

The study identifies multifaceted evidence of a possible functional effect for rs1318920.

The racial and ethnic diversity of the US, including among patients receiving their care at the Veterans Health Administration (VHA), is increasing. Dementia is a significant public health challenge and may have greater incidence among older adults from underrepresented racial and ethnic minority groups.

To determine dementia incidence across 5 racial and ethnic groups and by US geographical region within a large, diverse, national cohort of older veterans who received care in the largest integrated health care system in the US.

Retrospective cohort study within the VHA of a random sample (5% sample selected for each fiscal year) of 1 869 090 participants aged 55 years or older evaluated from October 1, 1999, to September 30, 2019 (the date of final follow-up).

Self-reported racial and ethnic data were obtained from the National Patient Care Database. US region was determined using Centers for Disease Control and Prevention (CDC) regions from residential zip codes.

Incident diagnosis of dementia (9t CI, 1.13-1.28) for Asian participants, 1.54 (95% CI, 1.51-1.57) for Black participants, and 1.92 (95% CI, 1.82-2.02) for Hispanic participants. Across most US regions, age-adjusted dementia incidence rates were highest for Black and Hispanic participants, with rates similar among American Indian or Alaska Native, Asian, and White participants.

Among older adults who received care at VHA medical centers, there were significant differences in dementia incidence based on race and ethnicity. CDK inhibitor drugs Further research is needed to understand the mechanisms responsible for these differences.

Among older adults who received care at VHA medical centers, there were significant differences in dementia incidence based on race and ethnicity. Further research is needed to understand the mechanisms responsible for these differences.CD36 is a type 2 cell surface scavenger receptor widely expressed in many immune and non-immune cells. It functions as both a signaling receptor responding to DAMPs and PAMPs, as well as a long chain free fatty acid transporter. Recent studies have indicated that CD36 can integrate cell signaling and metabolic pathways through its dual functions and thereby influence immune cell differentiation and activation, and ultimately help determine cell fate. Its expression along with its dual functions in both innate and adaptive immune cells contribute to pathogenesis of common diseases, including atherosclerosis and tumor progression, which makes CD36 and its downstream effectors potential therapeutic targets. This review comprehensively examines the dual functions of CD36 in a variety of immune cells, especially macrophages and T cells. We also briefly discuss CD36 function in non-immune cells, such as adipocytes and platelets, which impact the immune system via intercellular communication. Finally, outstanding questions in this field are provided for potential directions of future studies.

Myopes have a reduced ability to elicit transient axial eye shortening after imposed positive defocus, which may be due to changes in the biochemical signaling cascade controlling choroidal thickness. We have investigated whether reading with inverted text contrast can still elicit transient axial eye shortening in myopes, like it has been shown in emmetropes.

Changes in axial length before and after reading were measured with the Lenstar LS-900. Text with inverted contrast was read from a large screen at 2 m distance (angular subtense 35.9°, screen luminance matched in all conditions to 86 ± 7 cd/m²) for 30 minutes. Moreover, we investigated the effects of letter sizes. Two text sizes were tested "small" text (letter height 13.75arcmin) and "large" text (letter height 34.39arcmin).

Reading text with inverted contrast induced eye shortening (-10.2 ± 9.5µm) in myopic eyes (n = 11; refraction -3.5 ± 1.9 diopters [D]), showing that an inhibitory signal was still generated by the retina as in emmetropes. In 15 subjects (refraction +1.7 to -4.2D) we found that small text does not elicit significant differences in axial length (P = 0.09). However, with large text, changes in axial length were clearly different for the both contrast polarities (standard contrast, +1.7 ± 9.0µm; inverted contrast, -9.7 ± 8.9µm; P = 0.0017).

Although positive defocus may not be an effective intervention to inhibit further eye growth in myopes, other visual stimuli can still trigger choroidal thickening and possibly generate signals to decrease myopia progression.

Our results have shown the optimized text features, which may have a positive impact on myopia control.

Our results have shown the optimized text features, which may have a positive impact on myopia control.

The purpose of this study was to compare concordance between ganglion cell-inner plexiform layer (GCIPL) data from the Cirrus optical coherence tomographer (OCT) Ganglion Cell Analysis (GCA) and visual fields (VFs), with and without Drasdo displacement.

From 296 open-angle glaucoma participants, GCIPL deviation and raw thickness data were extracted over locations per the 10-2 VF test grid, with and without application of Drasdo displacement, with global and eccentricity-dependent sensitivities and specificities calculated for both. With OCT and VF data classified as within or outside normative limits, pattern deviation values were compared using paired t-tests and Spearman correlations. Regression models were applied to pattern deviation values as a function of GCIPL thickness, and differences in model performance with and without displacement were compared using extra sums-of-squares F tests.

There were small but significant improvements in global specificity without displacement (0.58-0.59 with displag Drasdo displacement on probability-based reports is unlikely to alter clinical impressions of structure-function concordance, but applying displacement with GCIPL thickness data may improve detection of structure-function concordance.The origin of flowering plants (angiosperms) was one of the most transformative events in the history of our planet. Despite considerable interest from multiple research fields, numerous questions remain, including the age of the group as a whole. Recent studies have reported a perplexing range of estimates for the crown-group age of angiosperms, from ~140 million years (Ma; Early Cretaceous) to 270 Ma (Permian). Both ends of the spectrum are now supported by both macroevolutionary analyses of the fossil record and fossil-calibrated molecular dating analyses. Here, we first clarify and distinguish among the three ages of angiosperms the age of their divergence with acrogymnosperms (stem age); the age(s) of emergence of their unique, distinctive features including flowers (morphological age); and the age of the most recent common ancestor of all their living species (crown age). We then demonstrate, based on recent studies, that fossil-calibrated molecular dating estimates of the crown-group age of angiosperms have little to do with either the amount of molecular data or the number of internal fossil calibrations included. Instead, we argue that this age is almost entirely conditioned by its own prior distribution (typically a calibration density set by the user in Bayesian analyses). Lastly, we discuss which future discoveries or novel types of analyses are most likely to bring more definitive answers. In the meantime, we propose that the age of angiosperms is best described as largely unknown (140-270 Ma) and that contrasting age estimates in the literature mostly reflect conflicting prior distributions. We also suggest that future work that depends on the time scale of flowering plant diversification be designed to integrate over this vexing uncertainty.

The College of American Pathologists (CAP), a laboratory accreditation organization with deemed status under the Clinical Laboratories Improvement Amendments of 1988 administers accreditation checklists. Checklists are used by laboratories to ensure regulatory compliance. Peer-level laboratory professionals audit laboratory records during inspections to assess compliance.

To identify the most frequently cited deficiencies for molecular oncology laboratories undergoing CAP accreditation inspections and describe laboratory improvement opportunities.

The CAP Molecular Oncology Committee (MOC), which is involved in maintaining the Molecular Pathology checklist, reviewed data and inspector comments associated with the most frequently observed citations related to molecular oncology testing from laboratories inspected by the CAP during a 2-year period (2018-2020).

Of 422 molecular oncology laboratories that underwent accreditation inspections, 159 (37.7%) were not cited for any molecular oncology-related decludes a critical assessment of opportunities for laboratories to improve compliance and molecular oncology testing quality.

Alveolar soft part sarcoma is a rare soft tissue tumor involving mainly deep soft tissue of the lower extremities. Primary bone involvement is extremely rare.

To discuss histopathologic and immunohistochemical features of alveolar soft part sarcoma along with challenges in diagnosis and management in the context of primary bone origin.

Our study constituted 8 patients. Data were collected from the Tata Memorial Hospital, Mumbai, India, during a 10-year period.

Five patients in our study were female and 3 were male. Their ages ranged from 13 to 56 years. Primary bone involvement was seen in the humerus, tibia, fibula, radius, calcaneus, and rib. Radiologic impression was that of a primary malignant bone tumor in all patients. Conventional histopathologic features were seen in 7 of 8 patients. Positive immunohistochemical expression for TFE3 was demonstrated in 6 patients. All patients had distant metastasis either at presentation or later in the course of the disease. Surgical excision of the primary t diagnosis of alveolar soft part sarcoma. Aggressive behavior of this tumor and its refractoriness to conventional chemotherapy were evident from our series.

Sensitization to human leukocyte antigen is a barrier to. Few data have been published on desensitization using polyvalent human intravenous immunoglobulin (IVIG) alone.

We retrospectively reviewed the of 45 patients with a positive complement-dependent cytotoxicity crossmatch (CDCXM) or flow cytometry crossmatch (FCXM) against living donors from January 2003 to December 2014. Of these, 12 were excluded. Patients received monthly IVIG infusions (2 g/kg) only until they had a negative T-cell and B-cell FCXM.

During the 33 patients, 22 (66.7%) underwent living donor kidney transplantation, 7 (21.2%) received a deceased donor graft, and 4 (12.1%) did not undergo transplantation. The median class I and II panel reactive antibodies for these patients were 80.5% (range 61%-95%) and 83.0% (range 42%-94%), respectively. Patients (81.8%) had a positive T-cell and/or B-cell CDCXM and 4 (18.2%) had a positive T-cell and/or B-cell FCXM. Patients underwent transplantation after a median of 6 (range 3-16). The median donor-specific antibody mean fluorescence intensity sum was 5057 (range 2246-11,691) before and 1389 (range 934-2492) after desensitization (p = 0.0001). Mean patient follow-up time after transplantation was 60.5 (SD, 36.8) months. Nine patients (45.0%). Death-censored graft survival at 1, 3, and 5 years after transplant was 86.4, 86.4, and 79.2%, respectively and patient survival was 95.5, 95.5, and 83.7%, respectively.

Desensitization using IVIG alone is an effective strategy, allowing successful transplantation in 87.9% of these highly sensitized patients.

Desensitization using IVIG alone is an effective strategy, allowing successful transplantation in 87.9% of these highly sensitized patients.Despite their rarity in peripheral blood, basophils play important roles in allergic disorders and other diseases including sepsis and COVID-19. Existing basophil isolation methods require many manual steps and suffer from significant variability in purity and recovery. We report an integrated basophil isolation device (i-BID) in microfluidics for negative immunomagnetic selection of basophils directly from 100 μL of whole blood within 10 minutes. We use a simulation-driven pipeline to design a magnetic separation module to apply an exponentially increasing magnetic force to capture magnetically tagged non-basophils flowing through a microtubing sandwiched between magnetic flux concentrators sweeping across a Halbach array. The exponential profile captures non-basophils effectively while preventing their excessive initial buildup causing clogging. link2 The i-BID isolates basophils with a mean purity of 93.9% ± 3.6% and recovery of 95.6% ± 3.4% without causing basophil degradation or unintentional activation. Our i-BID has the potential to enable basophil-based point-of-care diagnostics such as rapid allergy assessment.Chiral organic-inorganic hybrid perovskites have gained extensive research interest due to their combination of chirality and the excellent optical, electrical and spin properties of perovskite materials, especially in two-dimensional hybrid perovskites. Herein, we report two-dimensional organic-inorganic perovskite enantiomeric ferroelectric [(R)-β-MPA]2CdCl4 (1) and [(S)-β-MPA]2CdCl4 (2) (MPA+ =methylphenethylammonium). Their mirror relationships are verified by both circular dichroism (CD) and crystal structures. At the same time, the two exhibit very similar ferroelectricity and related properties, including high Curie temperature (343 K), large spontaneous polarization (4.65 μC cm-2), and low coercive force field (13 kV cm-1). Unusually, at room temperature the crystal phase is monoclinic with the space group C2 and above the phase transition temperature it is triclinic with the space group P1, which means that the symmetry decreases with the increase of temperature. In addition, it exhibits a flexible switchable SHG response, while [(R)-β-MPA]2CdCl4 and [(S)-β-MPA]2CdCl4 have wide band gaps of 4.21 and 4.26 eV, respectively, mainly contributed by inorganic CdCl6 octahedra. This discovery opens a new way for the construction of two-dimensional enantiomeric molecular ferroelectrics.Herein, a bimetallic sulfide Fe0.4Co0.6S2@NC nanobox was prepared via a simple two-step synthetic route. The N-doped carbon coated hollow nanobox was derived from a Prussian blue analogue (PBA) and applied for an SIB anode. As expected, it exhibits a high capacity (486.6 mA h g-1 at 0.1 A g-1) and displays an excellent cycling stability (230 mA h g-1 at 10 A g-1 after 900 cycles).We investigated the effect of the adsorbed ions on the stability of nanobubbles suspended in the liquid in a recent article published in Physical Chemistry Chemical Physics. We calculated the electrostatic pressure using the classical electrical double layer (EDL) theory and pointed out that the electrostatic pressure is overestimated in previous theories due to the overlook of the stress in the diffusive double layer. Recently, S. I. Koshoridze and Yu. K. Levin questioned our calculations and results based on their intuition that diffusive ions in the EDL will drift and, therefore, not contribute to hydrostatic pressure. In this reply, we explain why mobile ions can also produce hydrostatic pressure from a hydrodynamic perspective.Correction for 'Is ethaline a deep eutectic solvent?' by Vira Agieienko et al., Phys. Chem. Chem. Phys., 2022, 24, 5265-5268, DOI https//doi.org/10.1039/D2CP00104G.p-Synephrine is the primary protoalkaloid found in Citrus species such as Citrus aurantium (bitter orange) and is widely used as a dietary supplement. Although studies have shown the anti-inflammatory effect of p-synephrine, the cells targeted and detailed mechanism(s) of action are not established. Therefore, we investigated the anti-inflammatory effects of p-synephrine and elucidated its underlying mechanisms in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, peritoneal macrophages, and an LPS-induced systemic inflammatory response syndrome (SIRS) mouse model. We found that p-synephrine inhibits the production of proinflammatory cytokines and nitric oxide in LPS-stimulated RAW264.7 cells, and proinflammatory cytokines in primary peritoneal macrophages. This effect of p-synephrine is due to downregulation of the p38 MAPK and NF-κB signaling pathway and is mediated by β-adrenergic receptors. Oral administration of p-synephrine to SIRS mice inhibited the serum levels of proinflammatory cytokines and improved their survival rate. Thus, our findings show that p-synephrine alleviates the hyperinflammatory response in macrophages and a SIRS mouse model.2'-O-Methyl (2'-OMe) antisense oligonucleotides (AOs) possessing a various number of 4-(trimethylammonio)butylsulfonyl or tosyl phosphoramidates (N+ and Ts-modifications, respectively) instead of a native phosphodiester linkage were designed to skip exon-23 in dystrophin pre-mRNA transcript in mdx mice myotubes. AOs bearing several zwitterionic N+ modifications in the sequence had remarkably increased thermal stability towards complementary mRNA in comparison with 2'-OMe-RNAs having negatively charged Ts and phosphorothioate (PS) linkages. However, only Ts-modified AOs exhibited a similar level of exon skipping in comparison with fully modified PS-containing 2'-OMe-RNA, whereas the exon skipping induced by N+ modified AOs was much lower with no exon-skipping detected for AOs having seven N+ modifications. The level of exon-skipping was improved once Ts and especially N+ moieties were used in combination with PS-modification, most likely through improved cellular and nuclear uptake of AOs. These results provide new insights on expanding the design of novel chemically modified AOs based on phosphate modifications.Metal-fullerene compounds are characterized by significant electron transfer to the fullerene cage, giving rise to an electric dipole moment. We use the method of electrostatic beam deflection to verify whether such reactions take place within superfluid helium nanodroplets between an embedded C60 molecule and either alkali (heliophobic) or rare-earth (heliophilic) atoms. The two cases lead to distinctly different outcomes C60Nan (n = 1-4) display no discernable dipole moment, while C60Yb is strongly polar. This suggests that the fullerene and small alkali clusters fail to form a charge-transfer bond in the helium matrix despite their strong van der Waals attraction. The C60Yb dipole moment, on the other hand, is in agreement with the value expected for an ionic complex.Ruthenium polypyridyl complexes have been widely used as bioprobes and photosensitizers. However, several disadvantages including slow cellular uptake, nonspecific binding with biomolecules and toxicity limit their applications. In this study, a nanocarrier of human serum albumin coated gold nanorods was developed to deliver a ruthenium photosensitizer for PDT/PTT combination therapy. The HSA coating endowed the nanodrug with high biocompatibility and stability under physiological conditions. Ru-GNR-HSANPs generate 1O2 and hydroxyl radicals to kill cancer cells under blue light irradiation, and exhibit excellent photothermal anticancer effects under 808 nm light irradiation. Significant synergistic anticancer effects were achieved by combined PDT/PTT therapy. Importantly, Ru-GNR-HSANPs can have the synergistic PDT/PTT functions with no need of drug release from the carrier.The aim of this study was to understand the influence of saltiness and sweetness intensity on oral processing behaviours of liquid, solid and composite foods. As salty foods, tomato sauce (liquid), penne pasta (solid) and their combination (composite food) were used at two levels of saltiness intensity (low/high). As sweet foods, strawberry sauce (liquid), milk gels (solid) and their combination (composite foods) were used at two levels of sweetness intensity (low/high). Saltiness, sweetness, hardness, chewiness, and liking were quantified using generalized labelled magnitude scales (gLMS). Oral processing behaviours were determined using video recordings (n = 39, mean age 25 ± 3 years) in a home-use-test (HUT) providing fixed bite sizes for all foods. As expected, taste intensity differed significantly between samples within the same food category. No significant effects of taste intensity on oral processing behaviours were found for sweet and salty foods. As expected, consistency strongly affected the consumption time per bite, number of chews per bite, number of chews per gram and eating rate. Solid foods were masticated for the longest time with the highest number of chews per bite, followed by composite foods as the liquid added to the solid foods enhanced lubrication. Liquid foods were masticated for the shortest time. We conclude that large differences in saltiness and sweetness intensity of liquid, solid and composite foods cause no differences in oral processing behaviours. We suggest that oral processing behaviours are primarily driven by texture, mechanical and lubrication properties of foods rather than by their taste intensity.The first copper-catalyzed direct dehydrative alkynylation of 2H-chromene hemiketals with terminal alkynes has been uncovered. The use of cheap and readily available CuCl2 as the catalyst allowed the preparation of various 2,2-disubstituted 2-alkynylated 2H-chromenes in moderate to good yields, which compensates for the limitation of the current methods only suited for the synthesis of 2-monosubsituted 2-alkynylated 2H-chromenes.Supramolecular chemistry and the chemistry of alkyl derivatives of the transition metals are both topics of considerable current interest, but the combination of the two fields is still underdeveloped. The challenges are, in large part, experimental in nature. For example, the self-assembly of molecules in supramolecular chemistry often relies on intermolecular hydrogen bonding, but most alkyl-transition metal bonds are cleaved by the protic groups used in hydrogen bond formation. Alkyl-platinum(IV) bonds are inert to protonolysis or attack by other electrophiles under mild conditions, and this has allowed an extensive supramolecular chemistry of organoplatinum(IV) complexes to be developed, as outlined in this perspective review. Highlights include a zeolitic structure, a polyrotaxane, a double helix, a nanotube structure and an example of spontaneous resolution to form a chiral sheet structure.Nanocarriers have emerged as one of the most promising approaches for drug delivery. Although several nanomaterials have been approved for clinical use, the translation from lab to clinic remains challenging. However, by implementing rational design strategies and using relevant models for their validation, these challenges are being addressed. This work describes the design of novel immunocompatible polymer nanocarriers made of melanin-mimetic polydopamine and Pluronic F127 units. The nanocarrier preparation was conducted under mild conditions, using a highly reproducible method that was tuned to provide a range of particle sizes ( less then 100 nm) without changing the composition of the carrier. A set of in vitro studies were conducted to provide a comprehensive assessment of the effect of carrier size (40, 60 and 100 nm) on immunocompatibility, viability and uptake into different pancreatic cancer cells varying in morphological and phenotypic characteristics. Pancreatic cancer is characterised by poor treatment efficacy and no improvement in patient survival in the last 40 years due to the complex biology of the solid tumour. High intra- and inter-tumoral heterogeneity and a dense tumour microenvironment limit diffusion and therapeutic response. The Pluronic-polydopamine nanocarriers were employed for the delivery of irinotecan active metabolite SN38, which is used in the treatment of pancreatic cancer. Increased antiproliferative effect was observed in all tested cell lines after administration of the drug encapsulated within the carrier, indicating the system's potential as a therapeutic agent for this hard-to-treat cancer.The legacy use of aqueous film-forming foam (AFFF) has led to the generation of large volumes of per- and poly-fluoroalkyl substances (PFAS)-contaminated asphalt materials, especially at airports and fire training areas. The management of such PFAS-contaminated asphalt materials requires an understanding of PFAS concentrations in these materials. This study, therefore, aimed to develop a suitable extraction methodology for the analysis of 22 target PFAS (i.e., carboxylic acids, sulfonic acids and fluorotelomers) in asphalt materials. link3 A series of experiments was conducted to optimise extraction solvent composition, as well as to assess the performance of the chosen method under various conditions (i.e., sonication temperature, PFAS contamination level, asphalt core composition and timing of stable isotope addition used as internal standard). The methanol-based extractants performed best due to their accuracy and precision, which were within the acceptable range (extraction efficiency between 70 and 130% and RSD less then 20%).