Treatment with broad-spectrum antifungal agents (e.g. itraconazole and efinaconazole) and other combination therapy (oral + oral and/or oral + topical) may be considerations in the management of NDM onychomycosis.This note studies the effect of the availability of a test for a virus on the public health of a population. It is shown by example that the existence of a freely available and moderately informative test for a virus may lower society’s welfare in comparison to the case where no test exists or access to the test is restricted. In this setting, any test provided to any subset of agents who would find it optimal not to isolate absent the test improves welfare.High-volume testing of clinical specimens for sexually transmitted diseases is performed frequently by a process known as group testing. This algorithmic process involves testing portions of specimens from separate individuals together as one unit (or „group”) to detect diseases. Retesting is performed on groups that test positively in order to differentiate between positive and negative individual specimens. The overall goal is to use the least number of tests possible across all individuals without sacrificing diagnostic accuracy. One of the most efficient group testing algorithms is array testing. In its simplest form, specimens are arranged into a grid-like structure so that row and column groups can be formed. Positive-testing rows/columns indicate which specimens to retest. With the growing use of multiplex assays, the increasing number of diseases tested by these assays, and the availability of subject-specific risk information, opportunities exist to make this testing process even more efficient. We propose specific specimen arrangements within an array that can reduce the number of retests needed when compared with other array testing algorithms. We examine how to calculate operating characteristics, including the expected number of tests and the SD for the number of tests, and then subsequently find a best arrangement. Our methods are illustrated for chlamydia and gonorrhea detection with the Aptima Combo 2 Assay. We also provide R functions to make our research accessible to laboratories.Finding chiral selector with high stereoselectivity to a variety of amino acid enantiomers remains a challenge and warrants further research. In this work, Taniaphos, a chiral ligand with rotatable spatial configuration, was employed as a chiral extractant to enantioseparate various amino acid enantiomers. Phenylalanine (Phe), homophenylalanine (Hphe), 4-nitrophenylalanine (Nphe), and 3-chloro-phenylglycine (Cpheg) were used as substrates to evaluate the extraction efficiency. The results revealed that Taniaphos-Cu exhibited good abilities to enantioseparate Phe, Hphe, Nphe, and Cpheg with the highest separation factors (α) of 3.13, 2.10, 2.32, and 2.14, respectively. Taniaphos-Cu is more conducive to combine with D-amino acid in extraction. The influences of pH, Taniaphos-Cu, and concentration and extraction temperature on extraction were comprehensively evaluated. The highest performance factors (pf) for Phe, Hphe, Nphe, and Cpheg at optimal extraction conditions were 0.08892, 0.1250, 0.09621, and 0.08021, respectively. The recognition mechanism between Taniaphos-Cu and amino acid enantiomers was discussed. The coordination interaction between Taniaphos-Cu and COO- , π-π interaction between Taniaphos-Cu and amino acid enantiomers are important acting forces in chiral extraction. The steric-hindrance between NH2 and OH lead to Taniaphos-Cu-D-Phe is more stable than Taniaphos-Cu-L-Phe. This work provided a chiral extractant that has good abilities to enantioseparate various amino acid enantiomers.Psoriasis has long been known as a disease with many complications, but was attributed to diet and obesity. However, in recent years, psoriasis itself has been recognized as a series of systemic inflammatory diseases, and that the cytokines involved can induce a variety of other diseases. Individuals with psoriasis were also found to have higher incidences of cerebral and cardiovascular diseases and a younger age at death compared to healthy individuals. However, no clear guidelines have been defined regarding how much vascular lesion testing should be performed in patients with psoriasis. In this report, I attempt to unravel the objective data on psoriasis and its complications from various reviews and reports, and introduce the impact of biologics, which are currently the main treatment for psoriasis, on cardiac vascular disease.

To characterize the shielding design and leakage radiation from a newly released ring gantry linac (Halcyon, Varian Medical Systems).

To assess the radiation leakage surrounding headshield and the radiation level after the beam stopper, measurements were made with GafChromic films. To evaluate the in-room radiation levels, the radiation leakage in the isocenter plane was measured with a large volume spherical ionization chamber (Exradin A6, Standard Imaging). A lead enclosure was constructed to shield the chamber from the low energy scatter radiation from the room. The radiation level at multiple locations was measured with the MLC fully closed and gantry at 0, 45, 90, 135, 180, 225, 270, and 315 degrees. The leakage radiation passing through multiple concrete slabs with various thickness was recorded in a narrow beam geometry to determine the tenth value layer (TVL).

A uniform leakage (<0.05%) at 1 m from electron beam line was measured surrounding the linac head with the maximum leakage measured atd measured near the edge of beam stopper. The leakage TVL values are derived and less than the values reported for conventional C-arm linac.

The reason why patients photosensitized to the drug ketoprofen (KP) may develop severe photoallergic skin reactions to octocrylene (OCT), an organic ultraviolet filter in sunscreens and cosmetics, remains largely unknown. OCT can be synthesized by using unsubstituted benzophenone (BP), a possible human carcinogen.

To verify if, and to what extent, BP residues are present in OCT-containing consumer products.

The raw material of OCT and 39 skincare products, of which 28 contain OCT, were chemically analysed for the presence of BP by means of liquid chromatography.

In the OCT raw material and in all 28 OCT-containing products the presence of BP could be demonstrated, mostly in concentrations above 10 ppm (0.001%), whereas a majority of OCT-free products (8/11, 73%) did not contain BP. Moreover, BP concentrations significantly increased, in a time- and temperature-dependent manner, likely due to the additional degradation of OCT.

Photoallergic contact dermatitis from OCT in patients photosensitized to KP might rely on residual BP impurities. Toxicological and ecological studies that evaluate the safety of OCT might also need to consider the concomitant presence of BP.

Photoallergic contact dermatitis from OCT in patients photosensitized to KP might rely on residual BP impurities. Toxicological and ecological studies that evaluate the safety of OCT might also need to consider the concomitant presence of BP.Permanent His bundle pacing (HBP) has rapidly been adapted into clinical practice in recent years as a physiologic pacing. The 3830 (Medtronic Inc, MN, USA) pacing lead commonly used for HBP is lumenless, and there are limited reports available on extraction of this lead. No data exists on transvenous lead extraction (TLE) of very old HBP lead. Concerns remain about injury to the conduction system during extraction and the lack of lumen for placing a locking stylet for TLE when powered sheaths are required. We reported a unique case of TLE of very old HBP lead (14 years and 3 months) and other two leads, such as passive atrial and passive right ventricular apex backup.Temperature extreme indices were analyzed for five continental regions of southern South America defined according to their climatic characteristics. Gridded observations, reanalysis, and global-coupled climate models from CMIP5 were used with the approach of temperature extreme trend attribution analysis on fixed-threshold and percentile-based temperature extremes indices defined by the Expert Team on Climate Change Detection and Indices (ETCCDI). The largest positive trends are exhibited in the tropical nights index, and a clear anthropogenic signal is evident in the subtropical region. In the subtropical central Andes, there is a decrease in the frost days index and increases in the tropical nights and summer days indices, and an anthropogenic signal is evident. In the Patagonian region, all trends from the historical runs were significant, while the ones from the natural experiment were nonsignificant, showing the marked effect of anthropogenic forcing in this region in the extreme temperature events. Projected changes in extreme indices for the 21st century are consistent with a warming climate, and larger changes are expected in the warm nights index.Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a key adaptor protein that regulates the NF-κB pathway, in which MALT1 functions as a scaffold protein and protease to trigger downstream signals. The abnormal expression of MALT1 is closely associated with lymphomagenesis and other diseases, including solid tumors and autoimmune diseases. MALT1 is the only protease in the underlying pathogenesis of these diseases, and its proteolytic activity can be pharmacologically regulated. Therefore, MALT1 is a potential and promising target for anti-lymphoma and other MALT1-related disease treatments. Currently, the development of MALT1 inhibitors is still in its early stages. This review presents an overview of MALT1, particularly its X-ray structures and biological functions, and elaborates on the pathogenesis of diseases associated with its dysregulation. We then summarize previously reported MALT1 inhibitors, focusing on their molecular structure, biological activity, structure-activity relationship, and limitations. Finally, we propose future research directions to accelerate the discovery of novel MALT1 inhibitors with clinical applications. Overall, this review provides a comprehensive and systematic overview of MALT1-related research advances and serves as a theoretical basis for drug discovery and research.Sclerosing cholangitis, characterized by biliary inflammation, fibrosis, and stricturing, remains one of the most challenging conditions of clinical hepatology. Geniposide (GE) has anti-inflammatory, hepatoprotective, and cholagogic effects. Whether GE provides inhibition on the development of sclerosing cholangitis is unknown. Here, we investigated the role of GE in a mouse model in which mice were fed with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 4 weeks to induce sclerosing cholangitis. The results demonstrated that the increased hepatic gene expressions of pro-inflammatory (IL-6, VCAM-1, MCP-1, and F4/80) and profibrogenic markers (Col1α1, Col1α2, TGF-β, and α-SMA) in DDC feeding mice were reversed after treatment with GE. GE also suppressed expressions of CK19 and Ki67 in DDC-fed mice, suggesting that GE could ameliorate DDC-induced hepatocytes and cholangiocytes proliferation. In addition, GE significantly increased bile acids (BAs) secretion in bile, which correlated with induced expressions of hepatic FXR, BAs secretion transporters (BSEP, MRP2, MDR1, and MDR2), and reduced CYP7A1 mRNA expression. Furthermore, higher expressions of ileal FXR-FGF15 signaling and reduced ASBT were also observed after GE treatment. Taken together, these data showed that GE could modulate inflammation, fibrosis, and BAs homeostasis in DDC-fed mice, which lead to efficiently delay the progression of sclerosing cholangitis.

Although bans or restrictions on alcohol advertising are recommended as one of the three most effective and cost-effective policies to curb alcohol consumption, the best evidence to support this is indirect. The aim of this study was to examine whether the complete ban on alcohol advertising in Norway in 1975 had any effect on total alcohol sales.

Annual time series of recorded alcohol sales (1960-2006) were analysed. Autoregressive integrated moving average interrupted time series techniques were used to model the effect of the advertising ban, adjusting for alcohol prices and wages.

The autoregressive integrated moving average analyses showed a negative and statistically significant effect of the ban on total recorded alcohol sales, suggesting an immediate and lasting reduction of 7.4% (P = 0.002).

The complete ban on alcohol advertising in 1975 in Norway reduced recorded alcohol sales. This suggests that the ban had a protective effect by reducing total alcohol consumption. The conclusion remains tentative because of possible effects of unrecorded alcohol consumption and marketing on social media and satellite TV channels.

The complete ban on alcohol advertising in 1975 in Norway reduced recorded alcohol sales. This suggests that the ban had a protective effect by reducing total alcohol consumption. The conclusion remains tentative because of possible effects of unrecorded alcohol consumption and marketing on social media and satellite TV channels.

Little is known about the impact of Placenta Accreta Spectrum (PAS) on quality of life (QoL). This study aims to explore QoL and sexual function after a pregnancy complicated by PAS.

Women who experienced a pregnancy complicated by PAS were invited to complete an online survey. Two validated surveys were completed Short Form 36 (SF-36) and Female Sexual Function Index (FSFI). The mean scores were calculated and were compared between women by pregnancy outcomes. Continuous variables were presented as mean (standard deviation (SD)) and were compared to assess for significance between groups using independent t-test and one-way analysis of variance. Categorical variables were compared using χ

test.

A total of 142 women responded to the survey. For the SF-36, physical health was significantly higher for women at 24-36months postpartum compared to those from 0-6months postpartum for physical functioning (mean difference 21.9 (95% confidence interval (CI) 10.2, 33.5), role limitation due to physical function (mean difference 32.1 (95% CI 9.4, 54.7)) and pain (mean difference 15.5 (95% CI 3.4, 30.9)). For the mental health domains, only vitality improved at 24-36months compared to the first sixmonths postpartum (mean difference 12.8 (95% CI 0.2, 25.5)). The mean FSFI score was 24.8 (±5.8), lower than the critical score of 26.5 indicating sexual dysfunction, and 56.8% (n=75), scored less than 26.5.

Women after a pregnancy complicated by PAS had high scores on the physical health domains of SF-36. The mental health scores were lower for all women regardless of time since birth.

Women after a pregnancy complicated by PAS had high scores on the physical health domains of SF-36. The mental health scores were lower for all women regardless of time since birth.Amyotrophic lateral sclerosis (ALS) is a neurological disease that starts at a focal point and gradually spreads to other parts of the nervous system. One of the main clinical symptoms of ALS is muscle weakness. To study spreading patterns of muscle weakness, we analyze spatiotemporal binary muscle strength data, which indicates whether observed muscle strengths are impaired or healthy. We propose a hidden Markov model-based approach that assumes the observed disease status depends on two latent disease states. The model enables us to estimate the incidence rate of ALS disease and the probability of disease state transition. Specifically, the latter is modeled by a logistic autoregression in that the spatial network of susceptible muscles follows a Markov process. The proposed model is flexible to allow both historical muscle conditions and their spatial relationships to be included in the analysis. To estimate the model parameters, we provide an iterative algorithm to maximize sparse-penalized likelihood with bias correction, and use the Viterbi algorithm to label hidden disease states. We apply the proposed approach to analyze the ALS patients’ data from EMPOWER Study.

To assess the chemical and microstructural characteristics of dentine after the use of two irrigation protocols and correlate this with the antimicrobial properties of hydraulic calcium silicate cement (HCSC) sealers and changes to the dentine structure/chemistry after sealer placement.

Two irrigation protocols – Protocol A using 2% NaOCl used 5mL/5min and Protocol B with 2% NaOCl (5mL/5min) followed by 17% EDTA (5mL/3min) – were used to prepare dentine. The chemical and microstructural changes following irrigation were assessed by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and Fourier transform infrared (FT-IR) spectroscopy (n=5) on dentine obtained from the mid-root and coronal parts of extracted human teeth. Four sealers (AH Plus, BioRoot, MTA Fillapex, TotalFill) were characterized by SEM/EDS (n=3). The ability of the sealers to eradicate intratubular Enterococcus faecalis biofilms was assessed by live/dead dye and confocal laser scanning microscopy to measure the percentbacterial load in the dentinal tubules than the other materials tested and the presence of smear layer did not affect its activity.

The removal of smear layer was necessary for penetration of AH Plus into the dentinal tubules. BioRoot was a more effective sealer in reducing the bacterial load in the dentinal tubules than the other materials tested and the presence of smear layer did not affect its activity.Feelings are conscious mental events that represent body states as they undergo homeostatic regulation. Feelings depend on the interoceptive nervous system (INS), a collection of peripheral and central pathways, nuclei and cortical regions which continuously sense chemical and anatomical changes in the organism. How such humoral and neural signals come to generate conscious mental states has been a major scientific question. The answer proposed here invokes (1) several distinctive and poorly known physiological features of the INS; and (2) a unique interaction between the body (the 'object’ of interoception) and the central nervous system (which generates the 'subject’ of interoception). The atypical traits of the INS and the direct interactions between neural and non-neural physiological compartments of the organism, neither of which is present in exteroceptive systems, plausibly explain the qualitative and subjective aspects of feelings, thus accounting for their conscious nature.

The objective of the present study was to identify the impact of systemic sclerosis (SSc) upon oral health-related quality of life (OHRQoL) of affected individuals resident in the UK.

A total of 100 patients and their partners or carers were invited to complete questionnaires regarding the impact of SSc on quality of life and psychological well-being using valid and reliable patient-reported outcome measures (OHIP-14, MHISS, OIDP, MDAS and HADS). A total of 50 patients with SSc and 18 partners or carers who acted as controls returned the completed questionnaires. Statistical analyses were performed for comparisons of different variables.

All the mean scores of OHIP-14 (SSc [16.5±12.4] Vs controls [6.06±7.6, p = 0.001]) and MHISS components were significantly higher in patients than those of control group (SSc [21.26±12] Vs controls [4.8±7.3, p<0.0001]). Majority of OIDP mean scores were significantly worse in patients compared with controls [SSc (10±8.7) Vs controls (1.72±3.4, p<0.0001)]. The mean of total MDAS [SSc (11.7±5.3) Vs controls (9.5±4.4)] and HADS scores were higher in patients compared to controls (SSc depression [4.8±3.3] and anxiety [6±4.6] Vs controls [3.7±3.1] [4.7±3.9]).

Although the present study is limited by the low response rate and its cross-sectional design, present results highlighted that systemic sclerosis has a negative impact on OHRQoL of the affected individuals; hence, the evaluation of associated psychological impact including anxiety and depression symptoms is needed to better understand, monitor and evaluate the disease comorbidity in patients with SSc.

Although the present study is limited by the low response rate and its cross-sectional design, present results highlighted that systemic sclerosis has a negative impact on OHRQoL of the affected individuals; hence, the evaluation of associated psychological impact including anxiety and depression symptoms is needed to better understand, monitor and evaluate the disease comorbidity in patients with SSc.Sleep disturbance is highly prevalent among shift-working nurses. We aimed to evaluate whether aerobic exercise (i.e., walking combined with jogging) improves objective sleep parameters among female nurses who met eligibility criterion as poor sleepers at the end of an 8-week exercise program and 4 weeks after study completion. This single-blinded, parallel-design, randomized controlled trial was conducted in a classroom of a hospital in northern Taiwan. Sixty eligible female nurses were randomly assigned to either the aerobic exercise (n = 30) or usual activity status (n = 30) group. A moderate-intensity aerobic exercise program was administered over 5 days (60 min per day) a week for 8 weeks after the nurses’ day shifts. Objective sleep outcomes including total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), and sleep efficiency (SE) were retrieved using an actigraph device. A generalized estimating equation model was used for data analysis. The aerobic exercise group exhibited improvements in TST and SE at 4 and 8 weeks compared with the baseline evaluation (TST B = 70.49 and 55.96; SE B = 5.21 and 3.98). Between-group differences were observed in SOL and WASO at 4 weeks but not 8 weeks compared with the baseline evaluation (SOL B = -7.18; WASO B = -11.38). Positive lasting effects for TST were observed only until the 4-week follow-up. To improve sleep quality and quantity, we encourage female nurses who sleep poorly to regularly perform moderate-intensity aerobic exercise.This experimental work reproduces the fipronil extra-label administration performed by producers in laying hens. The scientific goal was to characterize the residual concentrations in eggs from treated hens and suggest the withdrawal periods that should be respected to avoid risk for consumers. Thirty-four laying hens were allocated into two groups Group A was treated with fipronil in feed, two single doses of 1 mg kg-1 day-1 ; Group B was administered a single dose of 1 mg kg-1 by the topical route. Fipronil egg residues were quantified by HPLC-MS/MS. Fipronil and its sulphone metabolite (fipronil-SO2 ) were measured in egg after both treatments. The highest egg residual profile was always for fipronil-SO2 . Mean maximum egg concentrations (Cmax ) of 228.5 ± 79.8 ng/g (fipronil) and 1,849 ± 867 ng/g (fipronil-SO2 ) were found after fipronil administration in feed. The lowest residual levels were quantified after the topical treatment with Cmax of 27.1 ± 4.9 and 163 ± 26 ng/g for fipronil and fipronil-SO2 . Mean fipronil marker residues and established MRLs allowed calculating the withdrawal periods, the shortest being 74 days after topical administration. Such a long withdrawal period is difficult to meet in egg production systems. Thus, the extra-label use of fipronil in laying hens should not be recommended under any circumstances.

Obstetricians and gynaecologists (O&Gs) are at a risk of work-related musculoskeletal injuries (WRMI) on a daily basis.

To describe the prevalence of WRMI among O&Gs in Australia and New Zealand, explore risk factors for such injuries, and evaluate their impact.

An online survey of Fellows of Royal Australian and New Zealand College of Obstetricians and Gynaecologists was conducted in July 2016. It comprised questions on personal attributes, type of work, site and cause of WRMI, if any and treatment required.

We received responses from 765 O&Gs giving a response rate of 38.3% (765/1997). Four hundred and ten specialists (53.6%) reported suffering a WRMI at some point, including 252 (32.9%) who reported multiple injuries. In multivariable analysis, females had increased risk of WRMI (odds ratio (OR) 2.12; 95% CI 1.54-2.91) and among generalists and subspecialists, gynaecological oncologists had highest risk for WRMI (OR 3.13; 95% CI 1.21-8.14). Commonest sites of injury were back (218/633, 34.4%) and shoulder (131/633, 20.7%). Laparoscopic surgery (117/633, 18.5%) was the commonest cause of injury. Treatment was required for 88.6% of injuries (561/633) including 8.4% (53/633) of cases which required surgery. Ongoing symptoms post-injury were reported for 52.1% of injuries (330/633) and in 25.8% (163/633) of instances the practitioner needed to modify their scope of work.

This survey among a large cohort of O&Gs shows a high prevalence of WRMI with a profound negative impact on the practitioner and profession. There is a pressing need to advocate for improved ergonomics in their workplaces.

This survey among a large cohort of O&Gs shows a high prevalence of WRMI with a profound negative impact on the practitioner and profession. There is a pressing need to advocate for improved ergonomics in their workplaces.Scalp psoriasis is common and is often severe enough to negatively impact quality of life (QOL).1,2 In STYLE (NCT03123471), oral apremilast 30 mg twice daily (BID) demonstrated significantly greater improvements in moderate to severe plaque psoriasis of the scalp, scalp itch, whole body itch, and QOL versus placebo3 during the 16-week, placebo-controlled phase; safety and tolerability were consistent with the known safety profile of apremilast.3,4 We report the efficacy and safety of apremilast during the apremilast extension phase of STYLE (Weeks 16 to 32). During the extension phase, patients initially randomised to placebo were switched to apremilast (placebo/apremilast group; with titration during Week 16) and patients initially randomised to apremilast continued active treatment (apremilast/apremilast group; with dummy titration during Week 16) through Week 32. We also present efficacy of apremilast at Week 16 in patient subgroups based on baseline demographics and treatment characteristics.Much research has focused on the effects of pathogenic mitochondrial mutations on health. Notwithstanding, the mechanisms regulating the link between these mutations and their effects remain elusive in several cases. Here, we propose that certain mitochondrial mutations may disrupt function of a set of mitochondrial-transcribed small RNAs, perturbing communication between mitochondria and nucleus, leading to disease. Our hypothesis synthesises two lines of supporting evidence. First, several mitochondrial mutations cannot be directly linked to effects on energy production or protein synthesis. Second, emerging studies have described the existence of small RNAs encoded by the mitochondria and proposed their involvement in RNA interference. We present a roadmap to testing this hypothesis.Malaria is an infectious disease which disproportionately effects children and pregnant women. These vulnerable populations are often excluded from clinical trials resulting in one-size-fits-all treatment regimens based on those established for a nonpregnant adult population. Pharmacokinetic/pharmacodynamic (PK/PD) models can be used to optimize dose selection as they define the drug exposure-response relationship. Additionally, these models are able to identify patient characteristics that cause alterations in the expected PK/PD profiles and through simulations can recommend changes to dosing which compensate for the differences. In this review, we examine how PK/PD models have been applied to optimize antimalarial dosing recommendations for young children, including those who are malnourished, pregnant women, and individuals receiving concomitant therapies such as those for HIV treatment. The malaria field has had great success in utilizing PK/PD models as a foundation to update treatment guidelines and propose the next generation of dosing regimens to investigate in clinical trials. We propose how the malaria field can continue to use modeling to improve therapies by further integrating PK data into clinical studies and including data on drug resistance and host immunity in PK/PD models. Finally, we suggest that other disease areas can achieve similar success in applying pharmacometrics to improve outcomes by implementing three key principals.The high incidence and burden of pelvic pain are increasingly recognised in both the healthcare sector and by the general public. Current approaches to management assume that the diagnosis and remediation of identified lesions will ease this burden. The evidence base and successes in other areas of medicine would suggest that this assumption requires reconsideration.Extreme events such as drought and heatwaves are among the biggest challenges to agricultural production and food security. However, the effects of cropping systems on drought resistance of arable crops via their hydraulic behaviour remain unclear. We investigated how hydraulic traits of a field-grown pea-barley (Pisum sativum L. and Hordeum vulgare L.) mixture were affected by different cropping systems, that is, organic and conventional farming with intensive or conservation tillage. Xylem vulnerability to cavitation of both species was estimated by measuring the pressure inducing 50% loss of hydraulic conductivity (P50 ), while the water stress plants experienced in the field were assessed using native percentage loss of hydraulic conductivity (nPLC). Pea and barley showed contrasting hydraulic behaviours pea was less vulnerable to xylem cavitation and less stressed than barley; cropping systems affected the xylem vulnerability of barley, but not of pea. Barley grown under conventional farming with no tillage was more vulnerable and stressed than under organic farming with intensive tillage. nPLC proved to be a valuable indicator for plant water stress. Our results highlight the impact of cropping systems on crop xylem vulnerability and drought resistance, thus plant hydraulic traits, for protecting food security under future climate.Increasingly effective targeted precision medicine is either already available or in development for a number of genetic childhood movement disorders. Patient-centred, personalized approaches include the repurposing of existing treatments for specific conditions and the development of novel therapies that target the underlying genetic defect or disease mechanism. In tandem with these scientific advances, close collaboration between clinicians, researchers, affected families, and stakeholders in the wider community will be key to successfully delivering such precision therapies to children with movement disorders.Highly detailed physically based groundwater models are often applied to make predictions of system states under unknown forcing. The required analysis of uncertainty is often unfeasible due to the high computational demand. We combine two possible solution strategies (1) the use of faster surrogate models; and (2) a robust data worth analysis combining quick first-order second-moment uncertainty quantification with null-space Monte Carlo techniques to account for parametric uncertainty. A structurally and parametrically simplified model and a proper orthogonal decomposition (POD) surrogate are investigated. Data worth estimations by both surrogates are compared against estimates by a complex MODFLOW benchmark model of an aquifer in New Zealand. Data worth is defined as the change in post-calibration predictive uncertainty of groundwater head, river-groundwater exchange flux, and drain flux data, compared to the calibrated model. It incorporates existing observations, potential new measurements of system states („additional” data) as well as knowledge of model parameters („parametric” data). The data worth analysis is extended to account for non-uniqueness of model parameters by null-space Monte Carlo sampling. Data worth estimates of the surrogates and the benchmark suggest good agreement for both surrogates in estimating worth of existing data. The structural simplification surrogate only partially reproduces the worth of „additional” data and is unable to estimate „parametric” data, while the POD model is in agreement with the complex benchmark for both „additional” and „parametric” data. The variance of the POD data worth estimates suggests the need to account for parameter non-uniqueness, like presented here, for robust results.Agricultural water management (AWM) interventions play an important role in ensuring sustainable food production and mitigating climate risks. This study was carried out in a watershed located in a low rainfall (400-600 mm) region of western India. The Soil and Water Assessment Tool model was calibrated using surface runoff, soil loss, and reservoir storage levels, between the year 2000 and 2006. The investigation indicated that the various AWM interventions increased groundwater recharge from 30 mm/year to 80 mm/year and reduced surface runoff from 250 mm/year to 100 mm/year. The intervention structures were refilled two to three times during the monsoon season depending on rainfall intensity and duration. The interventions have the advantage of building a resilient system by enhancing groundwater availability even in dry years, stimulating crop intensification and protecting the landscape from severe erosion. The results indicate that soil erosion has been reduced by more than 75% compared to the nonintervention situation. Moreover, the AWM interventions led to the cultivation of 100-150 ha of fallow land with high-value crops (horticulture, vegetables, and fodder). Household income increased by several folds compared to the nonintervention situation. The study showed about 50% reduction in downstream water availability, which could be a major concern. However, there are a number of ecosystem trade-offs such as improved base flow to the stream and reduction in soil loss that should be considered. The study is of great importance to stakeholders to decide on the optimal design for AWM interventions to achieve sustainable development goals.

The slowly activating delayed rectifier K

channel (I

), composed of pore-forming KCNQ1 α-subunits and ancillary KCNE1 β-subunits, regulates ventricular repolarization in human heart. Propofol, at clinically used concentrations, modestly inhibits the intact (wild-type) I

channels and is therefore unlikely to appreciably prolong QT interval in ECG during anaesthesia. However, little information is available concerning the inhibitory effect of propofol on I

channel associated with its gene variants implicated in QT prolongation. The KCNE1 single nucleotide polymorphism leading to D85N is associated with drug-induced QT prolongation and therefore regarded as a clinically important genetic variant. This study examined whether KCNE1-D85N affects the sensitivity of I

to inhibition by propofol.

Whole-cell patch-clamp and immunostaining experiments were conducted in HEK293 cells and/or mouse cardiomyocyte-derived HL-1 cells, transfected with wild-type KCNQ1, wild-type or variant KCNE1 cDNAs.

Propofol i the possibility that the inhibitory action of anaesthetics on ionic currents becomes exaggerated in patients carrying variants in genes encoding ion channels.

This study aimed to clarify the different topographical distribution of tau pathology between progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) and establish a machine learning-based decision tree classifier.

Paraffin-embedded sections of the temporal cortex, motor cortex, caudate nucleus, globus pallidus, subthalamic nucleus, substantia nigra, red nucleus, and midbrain tectum from 1020 PSP and 199 CBD cases were assessed by phospho-tau immunohistochemistry. The severity of tau lesions (i.e., neurofibrillary tangle, coiled body, tufted astrocyte or astrocytic plaque, and tau threads) was semi-quantitatively scored in each region. Hierarchical cluster analysis was performed using tau pathology scores. A decision tree classifier was made with tau pathology scores using 914 cases. Cross-validation was done using 305 cases. An additional ten cases were used for a validation study.

Cluster analysis displayed two distinct clusters; the first cluster included only CBD, and the other cluster included all PSP and six CBD cases. We built a decision tree, which used only seven decision nodes. The scores of tau threads in the caudate nucleus were the most decisive factor for predicting CBD. In a cross-validation, 302 out of 305 cases were correctly diagnosed. In the pilot validation study, three investigators made a correct diagnosis in all cases using the decision tree.

Regardless of the morphology of astrocytic tau lesions, semi-quantitative tau pathology scores in select brain regions are sufficient to distinguish PSP and CBD. The decision tree simplifies neuropathologic differential diagnosis of PSP and CBD.

Regardless of the morphology of astrocytic tau lesions, semi-quantitative tau pathology scores in select brain regions are sufficient to distinguish PSP and CBD. The decision tree simplifies neuropathologic differential diagnosis of PSP and CBD.Guinea pigs have proved useful as experimental animal models in studying cerebellar anatomical and structural alterations in human neurological disease; however, they are also currently acquiring increasing veterinary interest as companion animals. The morphometric features of the normal cerebellum in guinea pigs have not been previously investigated using stereology. The objective of the present work was to establish normal volumetric and quantitative stereological parameters for cerebellar tissues in guinea pigs, by means of unbiased design-based stereology. Cerebellar total volume, gray and white matter volume fractions, molecular and granular layers volume fractions, cerebellar surface area, Purkinje cellular and nuclear volumes, and the Purkinje cell total count were stereologically estimated. For this purpose, cerebellar hemispheres from six adult male guinea pigs were employed. Isotropic, uniform random sections were obtained by applying the orientator method, and subsequently processed for light micro% and 37.4 ± 1.8% of total cerebellar volume respectively. The surface area of the cerebellum measured 611.4 ± 96.8 mm2 . Purkinje cells with a cellular volume of 3210.1 µm3 and with a nuclear volume of 470.9 µm3 had a higher incidence of occurrence. The mean total number of Purkinje cells for a cerebellar hemisphere was calculated to be 253,090 ± 34,754. The morphometric data emerging from the present study provide a set of reference data which might prove valuable as basic anatomical contribution for practical applications in veterinary neurology.Combination antiretroviral therapy (ART) can suppress plasma HIV-RNA to less then 50 copies/mL, decrease HIV transmission, reduce mortality, and improve quality of life for people living with HIV. ART cannot, however, eliminate HIV from an infected individual. The primary barrier to cure HIV infection is the multiple reservoir sites, including adipose tissue, bone marrow, central nervous system, liver, lungs, male and female reproductive system, secondary lymph nodes, and gut-associated lymphoid tissue, established 1 to 2 weeks after acquisition of HIV. Additional challenges include understanding the mechanism(s) by which HIV is maintained at low or undetectable levels and developing treatments that will eradicate or produce a sustained suppression of virus without ART. To date, the most extensive clinical investigations of cure strategies have been the shock-and-kill approach using histone deacetylase inhibitors (HDACis) to induce reactivation of latent HIV. Despite evidence for HIV latency reversal, HDACis alone have not decreased the size of the latent reservoir. Clinical pharmacologic explanations for these results include a low inhibitory quotient (i.e., low potency) within the reservoir sites and intrinsic (e.g., sex differences and reservoir size) and extrinsic (physiochemical and pharmacokinetic drug characteristics) factors. We offer an outline of desired clinical pharmacologic attributes for therapeutics intended for clinical HIV cure research and call for research teams to have early and ongoing involvement of clinical pharmacologists. We believe such a collective effort will provide a solid scientific basis and hope for reaching the goal of a cure for HIV infection.Glycosphingolipids are a structurally diverse class of lipids that regulate plasma membrane protein function. Rizzo et al (2021) now show that GOLPH3 promotes intra-Golgi transport of several enzymes that function at branching points of sphingolipid biosynthesis. By regulating the cellular sphingolipidome, GOLPH3 promotes growth factor signaling and cell proliferation, which may explain its oncogenic properties.

Cardiorespiratory fitness (CRF) has a strong inverse relationship with several chronic disease outcomes, including some cancers. The association between CRF and prostate cancer is controversial. We aimed to assess the prospective association of CRF with prostate cancer risk using a cohort study and review of the literature.

Cardiorespiratory fitness was assessed using a respiratory gas exchange analyser during exercise testing in 2204 cancer-free middle-aged men. Hazard ratios (HRs) with 95% confidence interval (CIs) were estimated. We corrected for within-person variability in CRF levels using repeat measurements.

During a median follow-up of 24.9years, 216 prostate cancer cases occurred. The age-adjusted regression dilution ratio of CRF was 0.58 (95% CI 0.53-0.64). The HR (95% CI) of prostate cancer per 1 standard deviation increase in CRF in age-adjusted analysis was 1.10 (0.95-1.27). The association remained consistent after further adjustment for several risk factors (HR 1.13; 95% CI 0.96-1.33). The corresponding adjusted HRs were 1.24 (95% CI 0.87-1.77) and 1.28 (95% CI 0.87-1.88), respectively, when comparing the extreme tertiles of CRF levels. Previous studies mostly reported no evidence of an association or an increased risk of prostate cancer in relation to high CRF. Studies reporting positive associations had short-term follow-up durations (<10years).

Primary data and a review of previous studies suggest that elevated CRF is not associated with reduced prostate cancer risk. Previous findings of significant evidence of associations could be attributed to increased screening and detection as well as reverse causation bias.

Primary data and a review of previous studies suggest that elevated CRF is not associated with reduced prostate cancer risk. Previous findings of significant evidence of associations could be attributed to increased screening and detection as well as reverse causation bias.

To describe the substance use and mental health characteristics of nurses who complete suicide compared to non-nurses.

Nurses are at higher risk of suicide than the general population. The relationship between substance use, mental health and suicide in a large sample of nurses in the USA has not been previously described.

Retrospective observational quantitative analysis.

Suicide data were retrospectively analysed in the Centers for Disease Control and Prevention National Violent Death Reporting System from 2003 to 2017. Data were compared between nurses who died by suicide (n=2,306) and non-nurses who died by suicide (n=185,620) using odds ratios calculations and chi-square test of proportions to detect independent risk factors of suicide completion in nurses. This study followed the STROBE guidelines.

Significant differences between nurses and non-nurses were found. Among decedents for whom substances were implicated as a cause of death, nurses were far more likely to be positive at the time of ded with seeking help all offer potential interventions to reduce nurse suicide.The transgender adult population is growing globally, but clinical pharmacology has lagged behind other areas of transgender medicine. Medical care for transgender adults may include long-term testosterone or estrogen treatment to align secondary sex characteristics with gender identity. Clinicians often use drug-drug interaction data from the general adult population to predict medication disposition or safety among transgender adults. However, this approach does not address the complex pharmacodynamic effects of hormone therapy in transgender adults. In this review, we critically examine sex-related and gender-related differences in clinical pharmacology and apply these data to discuss current gaps in transgender medicine.

To determine any independent influence of occlusal force and of number of natural teeth on decline in body mass index (BMI) among older Japanese adults.

Longitudinal study over a 3- to 6-year period.

Urban and rural area in Japan.

Independently living Japanese adults aged 69-71 years and 79-81 years at baseline. This analysis excluded participants who were defined as underweight at baseline.

Information was collected on age, gender, occlusal force, the number of teeth, BMI, socioeconomic factors, medical history, the number of daily prescription medications, cognitive function, depressive symptoms, hand grip strength, and physical function. Maximal occlusal force was measured with a pressure-sensitive sheet. Nutritional status was assessed using BMI, and participants with BMI <21.5 were defined as underweight. Then, they were divided into two groups a „BMI declined” group who were defined as underweight at either 3- or 6-year follow-up survey, and a „BMI maintained” group who were not defined as ecline in oral function is important to maintain nutritional status.Urinary tract infections (UTI) are among the most prevalent infectious diseases and the most common cause of nosocomial infections, worldwide. Uropathogenic E. coli (UPEC) are responsible for approximately 80% of all UTI, which most commonly affect the bladder. UPEC colonize the urinary tract by ascension of the urethra, followed by cell invasion, and proliferation inside and outside urothelial cells, thereby causing symptomatic infections and quiescent intracellular reservoirs that may lead to recurrence. Sugars, or glycans, are key molecules for host-pathogen interactions, and UTI are no exception. Surface glycans regulate many of the events associated with UPEC adhesion and infection, as well as induction of the host immune response. While the bacterial protein FimH binds mannose-containing host glycoproteins to initiate infection and UPEC-secreted polysaccharides block immune mechanisms to favour intracellular replication, host glycans on the urothelial surface and on secreted glycoproteins prevent or limit infection by inhibiting UPEC adhesion. Given the importance of glycans during UTI, here we review the glycobiology of UPEC infection to highlight fundamental sugar-mediated processes of immunological interest for their potential clinical applications. Interdisciplinary approaches incorporating glycomics and infection biology may help to develop novel non-antibiotic-based therapeutic strategies for bacterial infections as the spread of antimicrobial-resistant uropathogens is currently threatening modern healthcare systems.

Prurigo nodularis (PN) is associated with a variety of systemic comorbidities, including infectious diseases such as HIV and viral hepatitis. There are limited data on other infectious disease comorbidities in patients with PN.

To characterize infectious disease hospitalizations among patients with PN and the associated cost burden.

We searched the 2016-2017 National Inpatient Sample, a cross-sectional sample of 20% of all U.S. hospitalizations, for infectious disease hospitalizations among patients with PN. Associations of PN with infections and related costs were determined using multivariable logistic and linear regression adjusting for age, race, sex, and insurance type.

PN was associated with any infection overall (OR 2.98, 95% CI 2.49 – 3.56), as well as sepsis, HIV, cutaneous, hepatobiliary, CNS, bacterial, viral, and fungal/parasitic infections. PN patients had a higher mean cost of care ($11,667 vs. $8,893, P<0.001) and length of stay (5.5 days vs. 4.2 days, P<0.001) for any infection overall and 7 of 13 other infections. Adjusting for age, race, sex, and insurance coverage, PN was associated with higher cost (+30%, 95% CI +17% – +44%) and higher length of stay (+30%, 95% CI +18% – +44%) for any infection overall, as well as several other infections. These associations remained with alternate regression models adjusting for severity of illness.

There is a high infectious disease burden among PN patients, corresponding to higher healthcare utilization and spending. Clinicians must be aware of these associations when treating PN patients with immunomodulatory drugs.

There is a high infectious disease burden among PN patients, corresponding to higher healthcare utilization and spending. Clinicians must be aware of these associations when treating PN patients with immunomodulatory drugs.

Inlate 2019, the first cases of coronavirus disease 2019 (COVID-19) were reported in Wuhan, China, followed by a worldwide spread.Numerous countries have implemented control measures related to international travel, including border closures, travel restrictions, screening at borders, and quarantine of travellers.

To assess the effectivenessof international travel-related control measures during the COVID-19 pandemic on infectious disease transmission and screening-related outcomes.

We searched MEDLINE, Embase and COVID-19-specific databases, including the Cochrane COVID-19 Study Registerand the WHO Global Database on COVID-19 Research to 13 November 2020.

We considered experimental, quasi-experimental, observational and modelling studies assessing the effects of travel-related control measures affecting human travel across international borders during the COVID-19 pandemic. In the original review, we also considered evidence on severe acute respiratory syndrome (SARS) and Middle East respiratory syndported, employ a range of designs beyond modelling and assess potential benefits and harms of the travel-related control measures from a societal perspective.

The hybrid system combining a magnetic resonance imaging (MRI) scanner with a linear accelerator (Linac) has become increasingly desirable for tumor treatment because of excellent soft tissue contrast and nonionizing radiation. However, image distortions caused by gradient nonlinearity (GNL) can have detrimental impacts on real-time radiotherapy using MRI-Linac systems, where accurate geometric information of tumors is essential.

In this work, we proposed a deep convolutional neural network-based method to efficiently recover undistorted images (ReUINet) for real-time image guidance. The ReUINet, based on the encoder-decoder structure, was created to learn the relationship between the undistorted images and distorted images. The ReUINet was pretrained and tested on a publically available brain MR image dataset acquired from 23 volunteers. Then, transfer learning was adopted to implement the pretrained model (i.e., network with optimal weights) on the experimental three-dimensional (3D) grid phantom and in-vivo pelvis image datasets acquired from the 1.