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Plant synthetic biology has the capability to provide solutions to global challenges in the production and supply of medicines. Recent advances in 'omics' technologies have accelerated gene discoveries in medicinal plant research so that even multistep biosynthetic pathways for bioactive plant natural products with high structural complexity can be reconstituted in heterologous plant expression systems more rapidly. This review provides an overview of concept and strategies used to produce high-value plant natural products in heterologous plant systems and highlights recent successes in engineering the biosynthesis of conventional and new medicines in alternative plant hosts., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Mindful eating is a promising strategy to address problematic eating behaviors; however, little is known about its applicability during pregnancy. No studies have examined the combined effects of mindful and practical eating skills on eating behaviors. Aim: We examined associations between mindful and practical eating skills and eating behaviors (nutritional intake and emotional eating) among pregnant women who received psychoeducation on healthy eating and pregnancies. Methods: Participants were racially-diverse pregnant women (14-42 years) from four clinical sites in Detroit, Michigan, and Nashville, Tennessee (N = 741). We conducted multiple linear regression to examine associations between mindful (hunger cues, satiety cues, mindful check-ins) and practical (food diary/journal, MyPlate method) eating skills and nutritional intake. We calculated residualized change scores to represent changes in the quality of nutritional intake from second to third trimester. We performed multiple logistic regression to examine associations between mindful and practical eating skills and emotional eating. Results: Women improved over time in eating behaviors (better nutrition, less emotional eating). Regular use of MyPlate was associated with better nutritional intake (unstandardized coefficient [B] = -0.61), but food diaries were not. We found a significant interaction in predicting emotional eating: For those regularly paying attention to hunger cues, some use of MyPlate (Adjusted Odds Ratio [AOR] = 0.39) and especially regular use of MyPlate (AOR = 0.13) reduced the likelihood of emotional eating during pregnancy. Conclusion: Enhancing both mindful and practical eating skills, such as paying attention to hunger cues, and using the MyPlate method, may facilitate pregnant women's ability to improve their eating behaviors., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Much inter-intra-tester kinematic and kinetic repeatability research exists, with a paucity investigating inter-laboratory equivalence. The objective of this research was to evaluate the inter-laboratory equivalence between time varying unplanned kinematics and moments of unplanned sidestepping (UnSS). Eight elite female athletes completed an established UnSS procedure motion capture laboratories in the UK and Australia. Three dimensional time varying unplanned sidestepping joint kinematics and moments were compared. Discrete variables were change of direction angles and velocity. Waveform data were compared using mean differences, 1D 95%CI and RMSE. Discrete variables were compared using 0D 95% CI. The mean differences and 95%CI for UnSS kinematics broadly supported equivalence between laboratories (RMSE≤5.1°). Excluding hip flexion/extension moments (RMSE = 1.04 Nm/kg), equivalence was also supported for time varying joint moments between laboratories (RMSE≤0.40 Nm/kg). Dependent variables typically used to characterise UnSS were also equivalent. When consistent experimental and modelling procedures are employed, consistent time varying UnSS lower limb joint kinematic and moment estimates between laboratories can be obtained. We therefore interpret these results as a support of equivalence, yet highlight the challenges of establishing between-laboratory experiments or data sharing, as well as establishing appropriate ranges of acceptable uncertainty. These findings are important for data sharing and multi-centre trials.

Background: Carcinoma of the breast, a prevailing factor in female mortality worldwide, involves dysregulation of lncRNAs and microRNAs., Aim: The main goal of this research was to predict and experimentally examine the LINC01405 expression status in breast cancer subtypes, along with investigation of its interaction with miR-29b and miR-497-5p that results in regulating PI3-Kinase, WNT, and TGF-beta signaling pathways., Methods and Results: We performed a meta-analysis of five GEO datasets, encompassing microarray and RNA-seq data, to identify differentially expressed genes. The Cancer Genome Atlas transcriptome dataset was also analyzed to determine essential gene modules, associated with different stages of breast cancer by weighted gene co-expression networks. In addition, networks of drug-gene interactions were constructed to explore potential treatment options. LINC01405 as a microRNA sponge was chosen and examined. furthermore, downstream target genes were discovered. Experimental validation consisted of plasmid constructs used in cell culture experiments, RT-qPCR for expression analysis, and cell cycle assays. Our bioinformatics findings showed higher LINC01405 expression in Basal-like triple-negative breast carcinoma. In contrast, lower expression in Luminal samples was observed compared with normal samples, which was consistently observed in both breast cancer tissues and cell lines. LINC01405 expression level was correlated with miR-29b and miR-497 levels. The MDA-MB-231 cell line demonstrated higher LINC01405 expression and lower miR-29b and miR-497 expression levels. However, SKBR3 and MCF7 cells had lower LINC01405 expression and higher miR-29b and miR-497 levels, suggesting a regulatory role for LINC01405 as a competing endogenous RNA. This was experimentally confirmed when LINC01405 was overexpressed in SKBR3 cells, and the common target genes of miR-29b and miR-497 were upregulated. Additionally, LINC01405 upregulation led to the increased cell populations, proliferation, and upregulation of critical cancer-related genes, including AKT1, AKT3, mTOR, WNT3A, SMAD3, CYCLIN D1, CYCLIN D2, BCL2, and GSK3B., Conclusion: We revealed the differential expression of LINC01405 in several types of breast cancer and its role in regulating signaling pathways, potentially via scavenging miRNAs. These findings clarified the role of LINC01405 in breast cancer development and identified potential therapeutic targets., (© 2024 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Introduction: Pregnancy is a major life event during which women may experience increased psychological distress and changes in eating behaviors. However, few studies have investigated the influence of psychological distress on pregnant women's eating behaviors. The primary objective of this prospective study was to examine the associations of changes in perceived stress and depressive symptoms with emotional eating and nutritional intake during pregnancy. In addition, we examined the direct and moderating effects of perceived social support., Methods: Participants were racially diverse pregnant women (14-42 years) from 4 clinical sites in Detroit, MI, and Nashville, TN (N = 678). We used multiple linear and logistic regression models to determine if changes in stress and depressive symptoms across pregnancy were associated with changes in emotional eating and nutritional intake. We examined residualized change in stress and depressive symptoms from second to third trimester of pregnancy; positive residualized change scores indicated increased stress and depressive symptoms., Results: Participants showed significant improvement in emotional eating and nutritional intake from second to third trimester of pregnancy (P < .001 for both). At second trimester, higher depressive symptoms were associated with a greater likelihood of emotional eating (P < .001) and worse nutritional intake (P = .044) at third trimester. Increased stress and depressive symptoms during pregnancy were both associated with increased risk, whereas increased perceived social support reduced risk of emotional eating at third trimester (stress: adjusted odds ratio [AOR], 1.17; 95% CI, 1.08-1.26; depressive symptoms: AOR, 1.05; 95% CI, 1.01-1.08; social support: AOR, 0.93; 95% CI, 0.88-0.99). None were associated with changes in nutritional intake. Perceived social support did not show any moderating effects., Discussion: Increased psychological distress during pregnancy may increase emotional eating. Efforts to promote healthy eating behaviors among pregnant women should consider and address mental health., (© 2023 by the American College of Nurse-Midwives.)

Human lifespan has increased from a median of 46.5 years in 1950 to 71.7 years in 2022. As people age, one of the inevitable consequences is a decline in kidney function and glomerular filtration rate (GFR) which can have direct or indirect effects on the pharmacokinetic and pharmacodynamic profiles of many drugs. Numerous equations have been developed to generate estimated GFR (eGFR) using the two principal biomarkers: serum creatinine and serum cystatin C. However, the trajectory of changes with aging is dissimilar in these equations. In addition, there is recognition that chronological age (lifespan) often does not reflect biological age (healthspan) as an essential parameter in kidney function equations. In the past decade, there has been an increasing interest in quantifying biological age and new commercially available assays have entered the marketplace. In this narrative review, we illustrate how dominant equations of eGFR model the fractional change in this parameter very differently across chronological age. In addition, we review various biological age indicators (aging clocks) and challenges to their application in clinical practice. Importantly, by comparing vancomycin's mean clearance as a drug with limited metabolism and unchanged elimination between two age milestones in some recent population pharmacokinetic models, we show how efforts to quantify kidney function in older adults optimally remain under-explored, particularly those at the upper end of their lifespan. We also propose considering new models that integrate biological age as a new pathway to improve precision drug dosing in older adults., (© 2023 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Patients with atypical anorexia nervosa (AAN) or anorexia nervosa (AN) with premorbid history of higher weight (PHW; median BMI ≥ 85th %ile) may report greater eating disorder (ED) pathology, anxiety, and depression, than patients with premorbid history of lower weight (PLW; mBMI <85th %ile). Less is known about caregiver attitudes or treatment outcome related to premorbid weight history. The current study examined associations between premorbid weight history and patient/caregiver factors at presentation, during treatment, and end of treatment among adolescents (N = 138) diagnosed with AN/AAN and their caregivers who received interdisciplinary ED treatment. The sample comprised adolescents with PHW (n = 58, 40.6 %) or PLW (n = 82, 59.4 %). Adolescents with PHW did not differ with regard to patient- or caregiver-reported ED symptoms, comorbid psychopathology, rates of treatment completion, and attainment of estimated body weight compared to PLW (ps > .05). Adolescents with PHW (vs. PLW) were more likely to be diagnosed with AAN (67.9 %, p < .001), identify as cisgender male (p < .001) and to have lost more weight prior to presentation (p < .001). Perceived caregiver burden was lower among adolescents with PHW vs. PLW (p < .001). Further research should expand on this preliminary study exploring associations between premorbid weight history on patient and caregiver factors at treatment presentation and conclusion to enhance the efficacy of evidence-based treatment across the weight-spectrum., Competing Interests: Declaration of competing interest Dr. Sarah Forsberg receives royalties from Routledge Press. Dr. Le Grange receives royalties from Guilford Press and Routledge, is co-director of the Training Institute for Child and Adolescent Eating Disorders, LLC., and a member of Equip Health Clinical Advisory Board. There are no other conflicts of interest to report., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Subtle impairments in instrumental activities of daily living (IADLs) can be a key predictor of disease progression and are considered central to functional independence. Mild cognitive impairment (MCI) is a syndrome associated with significant changes in cognitive function and mild impairment in complex functional abilities. The early detection of functional decline through the identification of IADL impairments can aid early intervention strategies. Digital health technology is an objective method of capturing IADL-related behaviors. However, it is unclear how these IADL-related behaviors have been digitally assessed in the literature and what differences can be observed between MCI and normal aging., Objective: This review aimed to identify the digital methods and metrics used to assess IADL-related behaviors in people with MCI and report any statistically significant differences in digital endpoints between MCI and normal aging and how these digital endpoints change over time., Methods: A total of 16,099 articles were identified from 8 databases (CINAHL, Embase, MEDLINE, ProQuest, PsycINFO, PubMed, Web of Science, and Scopus), out of which 15 were included in this review. The included studies must have used continuous remote digital measures to assess IADL-related behaviors in adults characterized as having MCI by clinical diagnosis or assessment. This review was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines., Results: Ambient technology was the most commonly used digital method to assess IADL-related behaviors in the included studies (14/15, 93%), with passive infrared motion sensors (5/15, 33%) and contact sensors (5/15, 33%) being the most prevalent types of methods. Digital technologies were used to assess IADL-related behaviors across 5 domains: activities outside of the home, everyday technology use, household and personal management, medication management, and orientation. Other recognized domains-culturally specific tasks and socialization and communication-were not assessed. Of the 79 metrics recorded among 11 types of technologies, 65 (82%) were used only once. There were inconsistent findings around differences in digital IADL endpoints across the cognitive spectrum, with limited longitudinal assessment of how they changed over time., Conclusions: Despite the broad range of metrics and methods used to digitally assess IADL-related behaviors in people with MCI, several IADLs relevant to functional decline were not studied. Measuring multiple IADL-related digital endpoints could offer more value than the measurement of discrete IADL outcomes alone to observe functional decline. Key recommendations include the development of suitable core metrics relevant to IADL-related behaviors that are based on clinically meaningful outcomes to aid the standardization and further validation of digital technologies against existing IADL measures. Increased longitudinal monitoring is necessary to capture changes in digital IADL endpoints over time in people with MCI., Trial Registration: PROSPERO International Prospective Register of Systematic Reviews CRD42022326861; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=326861., (©Lauren Lawson, Ríona Mc Ardle, Sarah Wilson, Emily Beswick, Radin Karimi, Sarah P Slight. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 25.07.2023.)

Multi-planar forces and moments are known to injure the anterior cruciate ligament (ACL). In ACL injury risk studies, however, the uni-planar frontal plane external knee abduction moment is frequently studied in isolation. This study aimed to determine if the frontal plane knee moment (KM-Y) could classify all individuals crossing a risk threshold compared to those classified by a multi-planar non-sagittal knee moment vector (KM-YZ). Recreationally active females completed three sports tasks-drop vertical jumps, single-leg drop vertical jumps and planned sidesteps. Peak knee abduction moments and peak non-sagittal resultant knee moments were obtained for each task, and a risk threshold of the sample mean plus 1.6 standard deviations was used for classification. A sensitivity analysis of the threshold from 1-2 standard deviations was also conducted. KM-Y did not identify all participants who crossed the risk threshold as the non-sagittal moment identified unique individuals. This result was consistent across tasks and threshold sensitivities. Analysing the peak uni-planar knee abduction moment alone is therefore likely overly reductionist, as this study demonstrates that a KM-YZ threshold identifies 'at risk' individuals that a KM-Y threshold does not. Multi-planar moment metrics such as KM-YZ may help facilitate the development of screening protocols across multiple tasks.

Plant alkaloids constitute an important class of bioactive chemicals with applications in medicine and agriculture. However, the knowledge gap of the diversity and biosynthesis of phytoalkaloids prevents systematic advances in biotechnology for engineered production of these high-value compounds. In particular, the identification of cytochrome P450s driving the structural diversity of phytoalkaloids has remained challenging. Here, we use a combination of reverse genetics with discovery metabolomics and multivariate statistical analysis followed by in planta transient assays to investigate alkaloid diversity and functionally characterize two candidate cytochrome P450s genes from Atropa belladonna without a priori knowledge of their functions or information regarding the identities of key pathway intermediates. This approach uncovered a largely unexplored root localized alkaloid sub-network that relies on pseudotropine as precursor. The two cytochrome P450s catalyze N-demethylation and ring-hydroxylation reactions within the early steps in the biosynthesis of diverse N-demethylated modified tropane alkaloids., (© 2022. The Author(s).)

A woman who is infertile is defined as a woman who is unable to conceive after having unprotected sex for more than one year. 20-25% of couples worldwide suffer from infertility each year (60 to 80 million couples). In vitro fertilization (IVF) plays a significant role in the treatment of various types of infertility, including fallopian tube defects, endometriosis, immunity, and male causes. IVF is a complex procedure that can be used to aid fertility or prevent genetic problems in the fetus. The objective of this review is to investigate factors that affect IVF failure and success rates. Need for this review is predicated on the different results obtained from previous studies, the high prevalence of infertility, and the lack of a similar study in this field. Articles were regarded as suitable if they evaluated the association between any factor and IVF outcome. A comprehensive search of databases was completed from their inception until March 2021. Our search resulted in 1278 articles. After assessing the titles and abstracts, we selected 70 articles for further reading. Our review shows that the effectiveness of IVF treatment depends on many factors. These include the physical environment, genetics, psychological factors, serum levels of certain hormones, sperm characteristics, as well as the age and body mass index of couples. Based on the results of our study, nutrient supplementation maybe beneficial for the enhancement of semen quality. For better IVF outcome, it is better for obese women to balance their body mass index (BMI) before IVF procedure initiation., Competing Interests: The authors declare no conflicts of interest., (Copyright© by Royan Institute. All rights reserved.)

Nanoparticles are a promising solution for delivery of a wide range of medicines and vaccines. Optimizing their design depends on being able to resolve, understand, and predict biophysical and therapeutic properties, as a function of design parameters. While existing tools have made great progress, gaps in understanding remain because of the inability to make detailed measurements of multiple correlated properties. Typically, an average measurement is made across a heterogeneous population, obscuring potentially important information. In this work, we develop and apply a method for characterizing nanoparticles with single-particle resolution. We use convex lens-induced confinement (CLiC) microscopy to isolate and quantify the diffusive trajectories and fluorescent intensities of individual nanoparticles trapped in microwells for long times. First, we benchmark detailed measurements of fluorescent polystyrene nanoparticles against prior data to validate our approach. Second, we apply our method to investigate the size and loading properties of lipid nanoparticle (LNP) vehicles containing silencing RNA (siRNA), as a function of lipid formulation, solution pH, and drug-loading. By taking a comprehensive look at the correlation between the intensity and size measurements, we gain insights into LNP structure and how the siRNA is distributed in the LNP. Beyond introducing an analytic for size and loading, this work allows for future studies of dynamics with single-particle resolution, such as LNP fusion and drug-release kinetics. The prime contribution of this work is to better understand the connections between microscopic and macroscopic properties of drug-delivery vehicles, enabling and accelerating their discovery and development.

Barcodes are playing a significant role in different industries in the recent years and among the two most popular 2D barcodes, the QR code has grown exponentially. The QR-DN1.0 dataset includes 5 categories of QR codes that will cover low to high density levels. Each group has 15 QR codes: 5 images for testing and 10 images for training. After embedding the QRs into 30 color images using blind watermarking techniques and then extracting the QRs from the images taken with the mobile phone camera with three different methods, we will have three groups of 2250 extracted QR images, which provides a total of 6750 distorted and noisy QR images. In each of the mentioned three categories, the data is divided into two parts: testing, with 750 images, and training, with 2250 images. For every distorted QR in the dataset, a non-distorted instance of it is placed as a ground truth. One of the advantages of this data set is that it is real. Because no simulated noise has been added to the images and this dataset is completely derived from the real word challenge of extracting embedded QRs in color images captured from the watermarked image on the screen. It also includes various types of QRs such as single character, short sentence, long sentence, URL and location., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier Inc.)

Computer-aided drug design provides broad structural modifications to evolving bioactive molecules without an immediate requirement to observe synthetic restraints or tedious protocols. Subsequently, the most promising guidelines with regard to synthetic and biological resources may be focused on upcoming steps. Molecular docking is common in-silico drug design techniques since it predicts ligand-receptor interaction modes and associated binding affinities. Current docking simulations suffer serious constraints in estimating accurate ligand-receptor binding affinities despite several advantages and historical results. Response surface method (RSM) is an efficient statistical approach for modeling and optimization of various pharmaceutical systems. With the aim of unveiling the full potential of RSM in optimizing molecular docking simulations, this study particularly focused on binding affinity prediction of citalopram-serotonin transporter (SERT) and donepezil-acetyl cholinesterase (AChE) complexes. For this purpose, Box-Behnken design of experiments (DOE) was used to develop a trial matrix for simultaneous variations of AutoDock4.2 driven binding affinity data with selected factor levels. Responses of all docking trials were considered as estimated protein inhibition constants with regard to validated data for each drug. The output matrix was subjected to statistical analysis and constructing polynomial quadratic models. Numerical optimization steps to attain ideal docking accuracies revealed that more accurate results might be envisaged through the best combination of factor levels and considering factor interactions. Results of the current study indicated that the application of RSM in molecular docking simulations might lead to optimized docking protocols with more stable estimates of ligand-target interactions and hence better correlation of in-silico in-vitro data.

No-go theorems have played an important role in the development and assessment of scientific theories. They have stopped whole research programmes and have given rise to strong ontological commitments. Given the importance they obviously have had in physics and philosophy of physics and the huge amount of literature on the consequences of specific no-go theorems, there has been relatively little attention to the more abstract assessment of no-go theorems as a tool in theory development. We will here provide this abstract assessment of no-go theorems and conclude that the methodological implications one may draw from no-go theorems are in disagreement with the implications that have often been drawn from them in the history of science., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: To study the efficacy of shear wave elastography (SWE), using both qualitative and quantitative methods, alone and in conjunction with other B-mode features., Method: 117 patients with 123 nodules were studied both by conventional ultrasonography and SWE. Size, echogenicity, margins, internal calcification (micro- or macro-calcification), composition, shape and color Doppler were assessed for each nodule. The elasticity was assessed both qualitatively and quantitatively. Velocity in the ROI (Region of Interest) was calculated in the stiffest portions for 3 times, and maximum and mean velocity were obtained. ROC curve was analyzed to calculate the best cut-off value of the SWV (Shear Wave Velocity). Univariate logistic regression was used to examine the maximum and mean SWV as discrete variables and the results were compared to key variables of conventional US (Ultrasound) features., Result: 123 nodules in 117 patients were evaluated. Poor margins, hypoechogenicity, micro-calcification, color Doppler grades III and IV, color map grades IV and V, maximum and minimum velocity had significant correlation with malignancy. The highest Nagelkerke R2 belonged to maximum and mean velocity (R2 = 41.2 and 39 respectively) which propose them as the strongest predictors of malignancy. The best cut-off point for differentiation of benign from malignant nodules was 3.63 m/s for maximum velocity (sensitivity of 90 %, specificity of 78.2 %,) and 3.44 m/s for mean velocity (sensitivity of 90 %, specificity of 76.4 %)., Conclusion: The Real-time SWE is a promising test for the preoperative malignancy risk stratification of patients and maximum velocity has the strongest predictive value for both conventional and elastography variables., Competing Interests: Declaration of Competing Interest No potential conflicts of interest are disclosed., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The present study deals with optimizing, producing, characterizing, application and techno- economic analysis of oxidative enzymes [Laccase (Lac), manganese peroxidase (MnP), and lignin peroxidase (LiP)] from Aspergillus iizukae EAN605 in submerged fermentation process using pumpkin peels as a production substrate. The best operating parameters for producing Lac, MnP and LiP (6.15, 2.58 and 127.99 U mg -1 respectively) were recorded with 20 g 100 mL -1 of substrate, 4.6 mL 100 mL -1 of inoculum size at pH 5.5 after 10 days. The crude enzyme exhibited high stability at pH (3-9) and temperatures (20-60 °C). K m (Michaelis-Menten) of Lac, MnP and LiP crude enzyme was 2.25, 1.79 and 0.72 mM respectively. The decolourization of Remazol Brilliant Blue R by the crude enzyme was 84.84 %. The techno-economic analysis was assessed for a production unit with an annual operating time for enzymatic production and application is 7920 h/year and 100 m 3 of the capacity. The process would produce 27,000 cm 3 of crude enzyme with a price of USD 0.107 per cm 3 compared to USD 1 per cm 3 of the current commercial enzyme. The findings indicated that pumpkin peels have potential as a production substrate for oxidative enzymes from A. iizukae EAN605 and is economically feasible., Competing Interests: Declaration of Competing Interest The authors confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: Obesity has become a major, worldwide public health issue and is associated with a greater risk of adverse pregnancy outcomes. Leptin, a hormone produced by adipocytes, is elevated in individuals with obesity and may mediate the association between obesity and pregnancy outcomes. Though leptin levels during pregnancy have been associated with pregnancy outcomes, less is understood regarding preconception levels. Therefore, the objective of this study was to evaluate associations between preconception leptin levels and adverse pregnancy outcomes., Methods: This was a prospective cohort study nested within a large randomized controlled trial conducted at four medical centres in the United States. A total of 1078 women completed the parent study; this analysis involved women who became pregnant during that study (n = 776). Patients were healthy women, ages 18 to 40, attempting to conceive, with 1 to 2 prior pregnancy losses. Participants were followed for less than or equal to 6 cycles while trying to conceive and throughout pregnancy if they conceived. Preconception leptin concentrations were measured in serum collected at baseline then categorized by tertiles (using the lowest as reference group). Weighted log-binomial regression estimated risk ratios (RR) and 95% confidence intervals (CIs) for pregnancy loss, preterm delivery (PTD), gestational diabetes (GDM), and hypertensive disorders in pregnancy, adjusting for age, waist-to-hip ratio (WHR), and body mass index (BMI)., Results: The mean (SD) BMI in this cohort was 25.4 ± 6.0. GDM (RR 18.37; 95% CI, 2.39-141.55) and hypertensive disorders of pregnancy (RR 2.35; 95% CI, 1.20-4.61) risks were higher among women in the high tertile after adjusting for age and WHR. The associated risk persisted when adjusting for BMI for GDM but was attenuated for hypertensive disorders in pregnancy. Leptin levels were not associated with risk of pregnancy loss or PTD., Conclusions: Women with higher baseline preconception leptin levels had a higher likelihood of experiencing some adverse pregnancy outcomes including GDM and hypertensive disorders of pregnancy. These findings warrant further evaluation, especially in light of the association between leptin and obesity., Competing Interests: The authors declared no conflict of interest., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

New technologies have powered rapid advances in cellular imaging, genomics and phenotypic analysis in life sciences. However, most of these methods operate at sample population levels and provide statistical averages of aggregated data that fail to capture single-cell heterogeneity, complicating drug discovery and development. Here we demonstrate a new single-cell approach based on convex lens-induced confinement (CLiC) microscopy. We validated CLiC on yeast cells, demonstrating subcellular localization with an enhanced signal-to-noise and fluorescent signal detection sensitivity compared with traditional imaging. In the live-cell CLiC assay, cellular proliferation times were consistent with flask culture. Using methotrexate, we provide drug response data showing a fivefold cell size increase following drug exposure. Taken together, CLiC enables high-quality imaging of single-cell drug response and proliferation for extended observation periods.

The inactivation of antibiotic resistant Escherichia coli (Gram negative) and Staphylococcus aureus (Gram positive) seeded in greywater by bimetallic bio-nanoparticles was optimized by using response surface methodology (RSM). The bimetallic nanoparticles (Cu/Zn NPs) were synthesized in secondary metabolite of a novel fungal strain identified as Aspergillus iizukae EAN605 grown in pumpkin medium. Cu/Zn NPs were very effective for inhibiting growth of E. coli and S. aureus. The maximum inactivation was optimized with 0.028 mg mL-1 of Cu/Zn NPs, at pH 6 and after 60 min, at which the reduction of E. coli and S. aureus was 5.6 vs. 5.3 and 5.2 vs. 5.4 log reduction for actual and predicted values, respectively. The inactivation mechanism was described based on the analysis of untreated and treated bacterial cells by Field emission scanning electron microscopy (FESEM), Energy Dispersive X-Ray Spectroscopy (EDS), Atomic Force Microscopy (AFM) revealed a damage in the cell wall structure due to the effect of Cu/Zn NPs. Moreover, the Raman Spectroscopy showed that the Cu/Zn NPs led to degradation of carbohydrates and amino structures on the bacteria cell wall. The Fourier transform infrared spectroscopy (FTIR) analysis confirmed that the destruction take place in the C-C bond of the functional groups available in the bacterial cell wall. The techno economic analysis revealed that the biosynthesis Cu/Zn NPs is economically feasible. These findings demonstrated that Cu/Zn NPs can effectively inhibit pathogenic bacteria in the greywater., Competing Interests: The authors have declared that no competing interests exist.

The mint family (Lamiaceae) is well documented as a rich source of terpene natural products. More than 200 diterpene skeletons have been reported from mints, but biosynthetic pathways are known for just a few of these. We crossreferenced chemotaxonomic data with publicly available transcriptomes to select common selfheal (Prunella vulgaris) and its highly unusual vulgarisin diterpenoids as a case study for exploring the origins of diterpene skeletal diversity in Lamiaceae. Four terpene synthases (TPS) from the TPS-a subfamily, including two localised to the plastid, were cloned and functionally characterised. Previous examples of TPS-a enzymes from Lamiaceae were cytosolic and reported to act on the 15-carbon farnesyl diphosphate. Plastidial TPS-a enzymes using the 20-carbon geranylgeranyl diphosphate are known from other plant families, having apparently arisen independently in each family. All four new enzymes were found to be active on multiple prenyl-diphosphate substrates with different chain lengths and stereochemistries. One of the new enzymes catalysed the cyclisation of geranylgeranyl diphosphate into 11-hydroxy vulgarisane, the likely biosynthetic precursor of the vulgarisins. We uncovered the pathway to a rare diterpene skeleton. Our results support an emerging paradigm of substrate and compartment switching as important aspects of TPS evolution and diversification., (© 2019 The Authors. New Phytologist © 2019 New Phytologist Trust.)

Biomolecular condensates formed by liquid-liquid phase separation of proteins and nucleic acids have been recently discovered to be prevalent in biology. These dynamic condensates behave like biochemical reaction vessels, but little is known about their structural organization and biophysical properties, which are likely related to condensate size. Thus, it is critical that we study them on scales found in vivo. However, previous in vitro studies of condensate assembly and physical properties have involved condensates up to 1000 times larger than those found in vivo. Here, we apply confinement microscopy to visualize condensates and control their sizes by creating appropriate confinement length scales relevant to the cell environment. We observe anomalous diffusion of probe particles embedded within confined condensates, as well as heterogeneous dynamics in condensates formed from PEG/dextran and in ribonucleoprotein complexes of RNA and the RNA-binding protein Dhh1. We propose that the observed non-Gaussian dynamics indicate a hopping diffusion mechanism inside condensates. We also observe that, for dextran-rich condensates, but not for ribonucleo condensates, probe particle diffusion depends on condensate size.

We report a case of darunavir-induced cholestatic hepatitis in a human immunodeficiency virus (HIV)-infected patient in the third year of his combined antiretroviral therapy. During the patient's monthly follow-up with regard to his HIV infection, elevated transaminase levels were detected. The patient was subsequently hospitalised at the AIDS and gastroenterology departments. All tested viral hepatitis markers were negative. A diagnosis of autoimmune hepatitis was also ruled out. The liver biopsy revealed cholestatic hepatitis. Darunavir withdrawal resulted in a progressive decrease in liver enzyme levels. We highlight the importance of recognising late development of liver injury secondary to the use of darunavir, and the importance of monitoring liver function in patients undergoing prolonged treatment involving darunavir.

A growing body of research has explored well-being in diverse cultural contexts, and indicates that the definition and perception of well-being vary according to cultural context. Little is known, however, about whether intercultural differences in China (i.e., Tibetan and Han) lead to different perceptions of well-being and how social contexts and personal characteristics are associated with well-being in Tibetan and Han emerging adults. Using a self-determination framework, the current study examines the relationship between parental autonomy support (PAS) and psychological well-being (PWB) in Tibetan and Han emerging adults in China. Guided by implicit theory and self-regulatory theory, we propose a serial multiple mediation model of growth mindset and grit in the association between PAS and PWB. Propensity score matching was used to balance the two ethnic groups in terms of age, gender, socioeconomic status (SES), with a ratio of one to two. Finally, 59 Tibetan (71.2% girls) and 118 Han (69.5% girls) emerging adults aged from 18 to 25 years were included in the current study, and completed an online questionnaire survey. Findings suggest that (a) Tibetan emerging adults perceived higher levels of PWB than their peers from the Han ethnic group; (b) a serial multiple mediation model for the association between PAS and PWB was supported in Han emerging adults; (c) the indirect effects between PAS and PWB varied between Tibetan and Han emerging adults. Our findings suggest that PAS and grit contribute to PWB of emerging adults in both cultural contexts, whereas growth mindset may be beneficial for Han emerging adults only.

Cytosolic lipid droplets are endoplasmic reticulum-derived organelles typically found in seeds as reservoirs for physiological energy and carbon to fuel germination. Here, we report synthetic biology approaches to co-produce high-value sesqui- or diterpenoids together with lipid droplets in plant leaves. The formation of cytosolic lipid droplets is enhanced in the transient Nicotiana benthamiana system through ectopic production of WRINKLED1, a key regulator of plastid fatty acid biosynthesis, and a microalgal lipid droplet surface protein. Engineering of the pathways providing the universal C5-building blocks for terpenoids and installation of terpenoid biosynthetic pathways through direction of the enzymes to native and non-native compartments boost the production of target terpenoids. We show that anchoring of distinct biosynthetic steps onto the surface of lipid droplets leads to efficient production of terpenoid scaffolds and functionalized terpenoids. The co-produced lipid droplets "trap" the terpenoids in the cells.

Context: Fatty acids (FAs) are important for reproductive processes, including steroidogenesis, though associations with fecundability, as measured by time to pregnancy (TTP), are unclear., Objective: To investigate the relationship between preconception plasma phospholipid FA (PPFA) levels and time to human chorionic gonadotropin-pregnancy among women with prior pregnancy loss., Design, Setting, and Participants: Prospective cohort of 1228 women attempting pregnancy (aged 18 to 40 years, with one or two prior pregnancy losses) followed for up to six cycles at four US university medical centers during 2006 to 2012. PPFA levels were measured at baseline., Main Outcome Measures: Associations with fecundability overall and by body mass index (BMI) group after adjusting for confounders were estimated using fecundability odds ratios (FORs) and 95% CIs. False discovery rate (FDR) was used to account for multiple comparisons., Results: Monounsaturated fatty acids (MUFAs) were associated with increased fecundability or shorter TTP [FOR, 1.08 (95% CI, 1.01 to 1.16) per unit increase in percentage of total FAs], whereas polyunsaturated fatty acids (PUFAs) were associated with decreased fecundability or longer TTP [FOR, 0.95 (95% CI, 0.91 to 1.00) per 1% change], though associations only remained significant after FDR adjustment among women with BMI <25 kg/m2. Saturated FA and trans FA were not associated with fecundability. Omega-3 FAs and omega-6 linoleic acid were not associated with fecundability., Conclusion: We observed associations between preconception MUFA and PUFA levels and fecundability among women with normal BMI, highlighting the importance of FA composition among normal-weight women with prior pregnancy loss.

The menace of cholera epidemic occurrence in Yemen was reported in early 2017. Recent reports revealed that an estimated 500,000 people are infected with cholera whereas 2,000 deaths have been reported in Yemen. Cholera is transmitted through contaminated water and food. Yemen is the least developed country among the Middle East countries in terms of wastewater and solid waste management. The population of Yemen is about 24.5 million and generates about 70-100 million m 3 of sewage. An estimated 7% of the population has sewerage systems. It has been revealed that 31.2 million m 3 of untreated sewage is used for irrigation purposes especially for vegetables and Khat trees. In addition, more than 70% of the population in Yemen has no potable water. They depend on water wells as a water source which are located close to sewage disposal sites. The present review focuses on the current status of water, wastewater as well as solid waste management in Yemen and their roles in the outbreak of cholera. Future prospects for waste management have been proposed.

Purpose: Spinal cord injury (SCI) results in accelerated bone mineral density (BMD) loss and disorganization of trabecular bone architecture. The mechanisms underlying post-SCI osteoporosis are complex and different from other types of osteoporosis. Findings of studies investigating efficacy of pharmacological or rehabilitative interventions in SCI-related osteoporosis are controversial. The aim of this study was to review the literature pertaining to prevention and evidence-based treatments of SCI-related osteoporosis., Methods: In this systematic review, MEDLINE, EMBASE, PubMed, and the Cochrane Library were used to identify papers from 1946 to December 31, 2015. The search strategy involved the following keywords: spinal cord injury, osteoporosis, and bone loss., Results: Finally, 56 studies were included according to the inclusion criteria. Only 16 randomized controlled trials (involving 368 patients) were found. We found following evidences for effectiveness of bisphosphonates in prevention of BMD loss in acute SCI: very low-quality evidence for clodronate and etidronate, low-quality evidence for alendronate, and moderate-quality evidence for zoledronic acid. Low-quality evidence showed no effectiveness for tiludronate. In chronic SCI cases, we found low-quality evidence for effectiveness of vitamin D 3 analogs combined with 1-alpha vitamin D 2 . However, low-quality inconsistent evidence exists for alendronate. For non-pharmacologic interventions, very low-quality evidence exists for effectiveness of standing with or without treadmill walking in acute SCI. Other low-quality evidences indicated that electrical stimulation, tilt-table standing, and ultrasound provide no significant effects. Very low-quality evidence did not show any benefit for low-intensity (3 days per week) cycling with functional electrical stimulator in chronic SCI., Conclusions: No recommendations can be made from this review, regarding overall low quality of evidence as a result of high risk of bias, low sample size in most of the studies, and notable heterogeneity in type of intervention, outcome measurement, and duration of treatment. Therefore, future high-quality RCT studies with higher sample sizes and more homogeneity are strongly recommended to provide high-quality evidence and make applicable recommendations for prevention and treatment of SCI-related bone loss.

Purpose: Beta-thalassemia major is a severe, congenital hematological disorder and, if untreated, leads to early mortality. Progress in therapeutical strategies improved clinical outcomes and life expectancy; however, increased survival led to the development of new disorders, including endocrinopathies. Little is known on the possible impairment of adrenocortical function, a potentially life-threatening condition, in long-term thalassaemic survivors. We therefore decided to assess adrenal reserve and the value of salivary cortisol during ACTH stimulation in the diagnosis of adrenocortical insufficiency in adult patients with β-thalassemia major., Methods: Cross-sectional study including 72 adults with β-thalassemia major. Patients were tested with 1 µg ACTH for serum and salivary cortisol., Results: Subnormal serum cortisol responses to ACTH stimulation (i.e., <500 nmol/l) were registered in 15 out of 72 patients. Salivary cortisol increased in parallel with serum cortisol and a clear-cut positive correlation was detected at each timepoint. Moreover, peak salivary cortisol values after ACTH stimulation were significantly lower in patients with impaired adrenal reserve (513.6 ± 52.33 vs. 914.1 ± 44.04 nmol/l p < 0.0001)., Conclusions: Our results attest to the need for testing for adrenal insufficiency among adult thalassaemic patients, as up to 20% presented impaired adrenal reserve. Salivary and serum cortisol levels during stimulation with ACTH were closely correlated and the use of salivary cortisol sampling during ACTH testing may represent a surrogate to serum cortisol in these patients.

Background: Overt thyroid dysfunction has been associated with adverse obstetric outcomes. However, less is known regarding subclinical hypothyroidism or thyroid autoimmunity and their relationship to pregnancy complications., Objective: The purpose of this study was to examine the association between prepregnancy anti-thyroid antibodies and subclinical hypothyroidism and preterm delivery, gestational diabetes mellitus, and preeclampsia., Study Design: We conducted a secondary analysis of a prospective cohort of 18- to 40-year-old women with 1-2 previous pregnancy losses (n=1193) who participated in a multicenter randomized, placebo-controlled trial of low-dose aspirin. Prepregnancy levels of thyroid-stimulating hormone, free thyroxine, thyroglobulin antibody, and thyroid peroxidase antibody were measured. Relative risks and 95% confidence intervals were estimated with the use of generalized linear models with adjustment for age and body mass index., Results: Among women with an ongoing pregnancy of >20 weeks estimated gestational age, there was no association between prepregnancy thyroid-stimulating hormone level (>2.5 vs ≤2.5 mIU/L) and preterm delivery (adjusted relative risk, 0.77; 95% confidence interval, 0.40-1.47), gestational diabetes mellitus (adjusted relative risk, 1.28; 95% confidence interval, 0.54-3.04), or preeclampsia (adjusted relative risk, 1.20; 95% confidence interval, 0.71-2.04). Similarly, among women with thyroid antibodies, there was no increase in the likelihood of preterm delivery (relative risk, 1.26; 95% confidence interval, 0.65-2.45), gestational diabetes mellitus (relative risk, 1.33; 95% confidence interval, 0.51-3.49), or preeclampsia (relative risk, 1.02; 95% confidence interval, 0.54-1.92), compared with women without these antibodies., Conclusion: Among women with 1-2 previous pregnancy losses, subclinical hypothyroidism and thyroid autoimmunity were not associated with an increased risk of preterm delivery, gestational diabetes mellitus, or preeclampsia. These data support current recommendations that low-risk asymptomatic women should not be screened routinely for thyroid dysfunction or autoimmunity., (Published by Elsevier Inc.)

Background: Ankle injuries are one of the most common complaints of patients presenting to emergency departments (ED). The Ottawa ankle rules (OAR) was introduced to help physicians to decide who may require x-ray for blunt injuries. The present study aimed at validating the four steps weight-bearing rule of OAR as a sole criterion. Methods: This prospective observational study was conducted on 214 patients with acute ankle injury who referred to 3 emergency departments over a 7-months period in 2008. Main outcome measures of this survey included the sensitivity, specificity, positive and negative predictive values, and the likelihood ratios (positive and negative) of the four steps weight-bearing rule. Results: In this study, 34 fractures were found among the patients. The decision rule had a sensitivity of 0.88 and specificity of 0.61 in detecting all midfoot and ankle fractures. Application of this rule by emergency medicine residents resulted in a 47% reduction in the use of midfoot and ankle radiography. Conclusion: Applying a four steps weight-bearing rule as a sole criterion to detect ankle fractures is not as accurate and sensitive as OAR. Solitary application of this rule may lead to an increasing number of missed fractures compared with OAR.

To reduce costly late-phase compound scrubbing, there has been an increased focus on assessing compounds within in vitro assays that predict properties of human safety liabilities, before preclinical in vivo studies. The aim of our study was to answer the questions that whether the toxicity risk of a series of 3-oxobutanamide derivatives could be predicted by using of human lymphocytes and their isolated mitochondria. Using biochemical and flow cytometry assessments, we demonstrated that exposure of lymphocytes and isolated mitochondria to five 3-oxobutanamide derivatives (1-5) did not exhibit remarkable toxicity at low concentrations (50-500μM) but toxicity could be observed at high concentrations (1000 and 2000μM), particularly for N-(5-(4-bromophenyl)-3-isoxazolyl)-3-oxobutanamide (4) and N-(2-benzothiazolyl)-3-oxo butanamide (5). Compounds 4, 5 and partly N-(5-methyl-3-isoxazol yl)-3-oxo butanamide (1) also showed a marked cellular and mitochondrial toxicity while compound 5 displayed superior toxicity. Compound 5 induced cytotoxicity on human blood lymphocytes which was associated with the generation of intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP) collapse, lysosomal membrane injury, lipid peroxidation and depletion of glutathione. Our results suggested that among assessed compounds, increased toxicity of compound 5 compared to other compounds could be likely attributed to the presence of bromine substituent in 5. Finally our findings proposed that using of antioxidants and mitochondrial/lysosomal protective agents could be beneficial in decreasing the toxicity of 5., (Copyright © 2017 Elsevier B.V. All rights reserved.)

On-chip microvalves regulate electrical and fluidic access to an array of nanopores integrated within microfluidic networks. This configuration allows for on-chip sequestration of biomolecular samples in various flow channels and analysis by independent nanopores., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Torsion of a nongravid uterus is rare, as most cases of uterine torsion occur during pregnancy. We report a case of a large ovarian cyst causing uterine torsion, infarction, and rupture. A 57-year-old woman presented with acute-onset abdominal pain and increasing abdominal girth over the past year. Contrast-enhanced computed tomography (CT) demonstrated axial rotation and swirling of the uterus and the mesenteric fat, leading to a preoperative diagnosis of uterine torsion. Laparotomy confirmed that the uterine corpus had undergone a 180-degree axial rotation, and further revealed uterine wall infarction and rupture into the endometrium as well as partial decapitation of the uterus from the cervix. The swirled appearance of the uterus, radiologically similar to the "whirlpool sign" seen in bowel volvulus, is an important CT finding to recognize, especially in view of the risk of irreversible ischemic complications this uncommon entity may inflict on the uterus.

The aim of this systematic review was (i) to identify neuromuscular markers that have been predictive of a primary non-contact ACL injury, (ii) to assess whether proposed risk factors have been supported or refuted in the literature from cohort and case-control studies, and (iii) to reflect on the body of research that aims at developing field based tools to assess risk through an association with these risk factors. Electronic searches were undertaken, of PubMed, SCOPUS, Web of Science, CINAHL and SPORTDiscus examining neuromuscular risk factors associated with ACL injury published between January 1990 and July 2015. The evidence supporting neuromuscular risk factors of ACL injury is limited where only 4 prospective cohort studies were found. Three of which looked into muscular capacity and one looked into muscular activation patterns but none of the studies found strong evidence of how muscular capacity or muscular activation deficits are a risk factor for a primary non-contact ACL injury. A number of factors associated to neural control and muscular capacity have been suggested to be related to non-contact ACL injury risk but the level of evidence supporting these risk factors remains often elusive, leaving researchers and practitioners uncertain when developing evidence-based injury prevention programs., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Camptothecin is a monoterpene indole alkaloid (MIA) used to produce semisynthetic antitumor drugs. We investigated camptothecin synthesis in Camptotheca acuminata by combining transcriptome and expression data with reverse genetics, biochemistry, and metabolite profiling. RNAi silencing of enzymes required for the indole and seco-iridoid (monoterpene) components identified transcriptional crosstalk coordinating their synthesis in roots. Metabolite profiling and labeling studies of wild-type and RNAi lines identified plausible intermediates for missing pathway steps and demonstrated nearly all camptothecin pathway intermediates are present as multiple isomers. Unlike previously characterized MIA-producing plants, C. acuminata does not synthesize 3-α(S)-strictosidine as its central MIA intermediate and instead uses an alternative seco-iridoid pathway that produces multiple isomers of strictosidinic acid. NMR analysis demonstrated that the two major strictosidinic acid isomers are (R) and (S) diastereomers at their glucosylated C21 positions. The presence of multiple diastereomers throughout the pathway is consistent with their use in synthesis before finally being resolved to a single camptothecin isomer after deglucosylation, much as a multilane highway allows parallel tracks to converge at a common destination. A model "diastereomer" pathway for camptothecin biosynthesis in C. acuminata is proposed that fundamentally differs from previously studied MIA pathways., (© 2016 American Society of Plant Biologists. All rights reserved.)

Background: Whilst many studies measure large numbers of biomechanical parameters and associate these to anterior cruciate ligament injury risk, they cannot be considered as anterior cruciate ligament injury risk factors without evidence from prospective studies. A review was conducted to systematically assess the in vivo biomechanical literature to identify biomechanical risk factors for non-contact anterior cruciate ligament injury during dynamic sports tasks; and to critically evaluate the research trends from retrospective and associative studies investigating non-contact anterior cruciate ligament injury risk., Methods: An electronic literature search was undertaken on studies examining in vivo biomechanical risk factors associated with non-contact anterior cruciate ligament injury. The relevant studies were assessed by classification; level 1 - a prospective cohort study, level 2 - a retrospective study or level 3 - an associative study., Findings: An initial search revealed 812 studies but this was reduced to 1 level 1 evidence study, 20 level 2 evidence studies and 175 level 3 evidence studies that met all inclusion criteria. Level 1 evidence showed that the knee abduction angle, knee abduction moment and ground reaction force were biomechanical risk factors. Nine level 2 studies and eighty-three level 3 studies used these to assess risk factors in their study. Inconsistencies in results and methods were observed in level 2 and 3 studies., Interpretation: There is a lack of high quality, prospective level 1 evidence related to biomechanical risk factors for non-contact anterior cruciate ligament injury. More prospective cohort studies are required to determine risk factors and provide improved prognostic capability., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Previous evidence supports a role for growth hormone (GH)-insulin-like growth factor (IGF)-I deficiency in the pathophysiology of osteopenia/osteoporosis in adult thalassemia. Moreover, serum IGF-II has never been studied in this clinical condition. Thus, we elected to study the GH secretory status and the levels of circulating somatomedins, correlating these parameters with bone mineral density (BMD) and biochemical markers of bone turnover. A hundred and thirty-nine normal weight adult thalassemic patients (72 men and 67 women) were studied. Lumbar and femoral neck BMD were measured in 106/139 patients. Sixty-eight patients underwent growth hormone releasing hormone plus arginine testing. Measurement of baseline IGF-I and IGF-II was performed in all patients, while osteocalcin, C-terminal telopeptide of type I collagen (CTx), and urinary cross-linked N-telopeptides of type I collagen (NTx) were assayed in 95 of them. Femoral and lumbar osteoporosis/Z score below the expected range for age were documented in 61.3 and in 56.6 % of patients, respectively. Severe GH deficiency (GHD) was demonstrated in 27.9 % of cases, whereas IGF-I SDS was low in 86.3 %. No thalassemic patients displayed circulating levels of IGF-II below the reference range. GH peaks were positively correlated with femoral, but not lumbar, Z score. No correlations were found between GH peaks and osteocalcin, CTx and NTx. GH peaks were positively correlated with IGF-I values, which in their turn displayed a positive correlation with osteocalcin, CTx, and NTx. No correlations emerged between IGF-I values and either femoral or lumbar Z scores. No correlations were found between IGF-II and any of the following parameters: GH peaks, osteocalcin, CTx, NTx, femoral Z score, and lumbar Z score. Our study, besides providing for the first time evidence of a normal IGF-II production in thalassemia, contributes to a better understanding of the involvement of the somatotropin-somatomedin axis in the pathophysiology of bone demineralization in this disease. In particular, the contribution of GHD to femoral osteoporosis appears to be likely mediated by locally produced rather than circulating IGF-I.

Objective: Interpersonal psychotherapy (IPT) is aimed at improving negative affect that is purported to contribute to the development and maintenance of loss-of-control (LOC) eating. Although youth who report LOC over eating tend to consume more snack-foods than those without LOC, it is unknown if IPT impacts objective energy intake., Methods: To test if IPT improves mood and eating in the laboratory, we examined a sample of 88 girls with LOC eating who were randomized to either IPT (n = 46) or a standard-of-care health education (HE) group program. At baseline, and 6-month (follow-up 1) and 1-year (follow-up 2) following the initiation of the groups, girls consumed lunch from a multi-item meal with an instruction designed to model a LOC episode. Girls also reported mood state immediately before each meal., Results: Girls in IPT experienced no significant changes in pre-meal state depressive affect, while girls in HE experienced a non-significant improvement by follow-up 1 and then returned to baseline by follow-up 2 (p < .04). We found no significant group difference for changes in total intake relative to girls' daily energy needs (p's ≥ .25). However, IPT reduced, while HE increased, the percentage of daily energy needs consumed from snack-foods by follow-up 2 (p = .04). Within-groups, HE increased their snack food intake from follow-up 1 to follow-up 2 (p = .01)., Conclusions: In adolescent girls with LOC, IPT did not change total intake at the test meal and was associated with reduced snack-food intake. Data are required to determine if IPT effectively prevents excess weight gain in the longer-term. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:490-498)., (© 2015 Wiley Periodicals, Inc.)

Nanopore arrays are fabricated by controlled dielectric breakdown (CBD) in solid-state membranes integrated within polydimethylsiloxane (PDMS) microfluidic devices. This technique enables the scalable production of independently addressable nanopores. By confining the electric field within the microfluidic architecture, nanopore fabrication is precisely localized and electrical noise is significantly reduced. Both DNA and protein molecules are detected to validate the performance of this sensing platform.

Gallbladder polyps (GBPs) are incidentally seen in 4% to 7% of adults on abdominal ultrasounds. Most GBPs are benign cholesterol polyps, adenomyomatosis, or inflammatory polyps. Currently, cholecystectomy is widely accepted as appropriate care for polyps 10 mm or larger as they present a higher risk for malignancy. However, the management of small polyps smaller than 10 mm has continued to be a dilemma to clinicians and radiologists. Many authors support a nonoperative approach with imaging follow-up for polyps smaller than 10 mm, as most have been shown to be benign. However, small polyps do have the potential to be neoplastic adenomas and become malignant. In this report, we will describe a case of a tiny GBP that subsequently developed into a 20-mm carcinoma over a period of 2 years.

Plastoquinone is a redox active lipid that serves as electron transporter in the bifunctional photosynthetic-respiratory transport chain of cyanobacteria. To examine the role of genes potentially involved in cyanobacterial plastoquinone biosynthesis, we have focused on three Synechocystis sp. PCC 6803 genes likely encoding a chorismate pyruvate-lyase (sll1797) and two 4-hydroxy-3-solanesylbenzoate decarboxylases (slr1099 and sll0936). The functions of the encoded proteins were investigated by complementation experiments with Escherichia coli mutants, by the in vitro enzyme assays with the recombinant proteins, and by the development of Synechocystis sp. single-gene knock-out mutants. Our results demonstrate that sll1797 encodes a chorismate pyruvate-lyase. In the respective knock-out mutant, plastoquinone was hardly detectable, and the mutant required 4-hydroxybenzoate for growth underlining the importance of chorismate pyruvate-lyase to initiate plastoquinone biosynthesis in cyanobacteria. The recombinant Slr1099 protein displayed decarboxylase activity and catalyzed in vitro the decarboxylation of 4-hydroxy-3-prenylbenzoate with different prenyl side chain lengths. In contrast to Slr1099, the recombinant Sll0936 protein did not show decarboxylase activity regardless of the conditions used. Inactivation of the sll0936 gene in Synechocystis sp., however, caused a drastic reduction in the plastoquinone content to levels very similar to those determined in the slr1099 knock-out mutant. This proves that not only slr1099 but also sll0936 is required for plastoquinone synthesis in the cyanobacterium. In summary, our data demonstrate that cyanobacteria produce plastoquinone exclusively via a pathway that is in the first reaction steps almost identical to ubiquinone biosynthesis in E. coli with conversion of chorismate to 4-hydroxybenzoate, which is then prenylated and decarboxylated.

The issue of medical errors is currently a global concern which places a heavy financial and emotional burden on communities. A clinical decision support system (CDSS) is an electronic system designed to support clinical decision making. Considering the increasing importance and use of Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT), we developed SNOMED-CT to implement it more efficiently in making smart history taking, decisions to perform lab tests and imaging, diagnosis and recommendations. To evaluate these capabilities in real clinical problems, a new CDSS was compiled, aimed at supporting decisions on patients with a chief complaint of low back pain (LBP). A number of LBP differential diagnoses as well as some recommended indications and contraindications published by guidelines, were inputted to the database. Future software based on this model would help physicians to do necessary assessments and recommendations and might improve patients' safety.

We present gravitational field-flow fractionation and hydrodynamic chromatography of colloids eluting through 18 μm microchannels. Using video microscopy and mesoscopic simulations, we investigate the average retention ratio of colloids with both a large specific weight and neutral buoyancy. We consider the entire range of colloid sizes, including particles that barely fit in the microchannel and nanoscopic particles. Ideal theory predicts four operational modes, from hydrodynamic chromatography to Faxén-mode field-flow fractionation. We experimentally demonstrate, for the first time, the existence of the Faxén-mode field-flow fractionation and the transition from hydrodynamic chromatography to normal-mode field-flow fractionation. Furthermore, video microscopy and simulations show that the retention ratios are largely reduced above the steric-inversion point, causing the variation of the retention ratio in the steric- and Faxén-mode regimes to be suppressed due to increased drag. We demonstrate that theory can accurately predict retention ratios if hydrodynamic interactions with the microchannel walls (wall drag) are added to the ideal theory. Rather than limiting the applicability, these effects allow the microfluidic channel size to be tuned to ensure high selectivity. Our findings indicate that particle velocimetry methods must account for the wall-induced lag when determining flow rates in highly confining systems.

Background: The use of non-standard motorcycle helmets has the potential to undermine multinational efforts aimed at reducing the burden of road traffic injuries associated with motorcycle crashes. However, little is known about the prevalence or factors associated with their use., Methods: Collaborating institutions in nine low- and middle-income countries undertook cross-sectional surveys, markets surveys, and reviewed legislation and enforcement practices around non-standard helmets., Findings: 5563 helmet-wearing motorcyclists were observed; 54% of the helmets did not appear to have a marker/sticker indicating that the helmet met required standards and interviewers judged that 49% of the helmets were likely to be non-standard helmets. 5088 (91%) of the motorcyclists agreed to be interviewed; those who had spent less than US$10 on their helmet were found to be at the greatest risk of wearing a non-standard helmet. Data were collected across 126 different retail outlets; across all countries, regardless of outlet type, standard helmets were generally 2-3 times more expensive than non-standard helmets. While seven of the nine countries had legislation prohibiting the use of non-standard helmets, only four had legislation prohibiting their manufacture or sale and only three had legislation prohibiting their import. Enforcement of any legislation appeared to be minimal., Interpretation: Our findings suggest that the widespread use of non-standard helmets in low- and middle-income countries may limit the potential gains of helmet use programmes. Strategies aimed at reducing the costs of standard helmets, combined with both legislation and enforcement, will be required to maximise the effects of existing campaigns.

Background & Aims: Refractory ascites (RA) affects 10% of patients with advanced cirrhosis and ascites. Usual therapy includes large volume paracentesis, and in selected patients, a transjugular portosystemic shunt (TIPS). These therapies may be associated with increased morbidity: paracentesis may induce circulatory dysfunction and impair quality of life and TIPS may induce encephalopathy and is associated with increased mortality in patients with severe liver dysfunction. We present the results of a multicenter, non-randomized trial to assess the safety and efficacy of a new automated pump system for treatment of RA., Methods: Forty patients at 9 centers (February 2010-June 2011) received an implanted pump for the automated removal of ascites from the peritoneal cavity into the bladder, from where it was eliminated through normal urination. Patients were followed-up for 6months. The primary study outcome was safety. Secondary outcomes included recurrence of tense ascites and pump performance., Results: Surgical complications occurred early in the study and became less frequent. The pump system removed 90% of the ascites and significantly reduced the median number of large volume paracentesis per month [3.4 (range 1-6) vs. 0.2 (range 0-4); p <0.01]. Cirrhosis-related adverse events decreased along follow-up., Conclusions: The automated pump seems an efficacious tool to move out ascites from the peritoneal cavity to the bladder. Its safety is still moderate, but a broad use in different countries will improve the surgical technique as well as the medical surveillance. A prospective randomized clinical trial vs. large volume paracentesis is underway to confirm these preliminary results., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)