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Abstract Eukaryotic transcription involves the synergistic interaction of many different proteins. However, the question remains how eukaryotic promoters achieve ultrasensitive or threshold responses to changes in the concentration or activity of a single transcription factor (TF). We show theoretically that by recruiting a histone‐modifying enzyme, a TF binding non‐cooperatively to a single site can change the balance between opposing positive feedback loops in histone modification to produce a large change in gene expression in response to a small change in concentration of the TF. This mechanism can also generate bistable promoter responses, allowing a gene to be on in some cells and off in others, despite the cells being in identical conditions. In addition, the system provides a simple means by which the activities of many TFs could be integrated at a promoter.

This article discusses the overlooked toxicity of non-carcinogenic polycyclic aromatic hydrocarbons (PAHs). PAHs are pollutants that are produced by natural and human processes, such as fires and sedimentary rocks. While heavy PAHs have been extensively studied for their carcinogenic effects, light PAHs have been poorly investigated. However, recent studies suggest that light PAHs may have neurotoxic effects. There is growing evidence that light PAHs can cross barriers to the brain and have negative effects on neurodevelopment and cognitive function. Further research is needed to better understand the mechanisms of light PAH toxicity. [Extracted from the article]

Purpose: Mining has been carried out in San Luis Potosi, Mexico, since 1592, which has led to severe pollution issues affecting both the environment and human health. To address this, remediation projects have been initiated to restore the soil and its ecosystem services. These efforts involve removing the contaminants and restoring the soil's health and quality. This study aims to assess the biochemical impact of soil remediation carried out in the field, on areas that have been heavily contaminated with heavy metals over a prolonged period. Methods: The enzymatic activity, physiological profile, structure, and microbial diversity were used as bioindicators to assess the remediation of soil and two reference soils. Results: The results indicated that Pb and As decreased, but not at levels indicated by Mexican regulations, Cd concentrations decreased to be below Mexican regulations, the enzymatic activity between the soil with and without remediation did not present significant differences, both with low activity, arylsulfatase was the one with the highest inhibition, and urease the most activated. The evolution of the physiological activity of the microorganisms was greater in the remediated soil. Normal values of evenness and diversity were observed in soils with and without remediation, likewise, the consumption of substrates initially was towards carbohydrates and amines/amides, but in the end, carboxylic acids and polymers were consumed. Conclusion: The remediation process shows positive results; the recovery of soil health is in progress. It was demonstrated that the bioindicators used were adequate to evaluate the soil remediation process. [ABSTRACT FROM AUTHOR]

A plasma-enhanced chemical vapour deposition process based on a micro-plasma working in argon/nitrogen mixture and using a bromide precursor is used to grow boron nitride. Without hydrogen (H2) in the reactive media, growth of amorphous boron nitride (a-BN) is observed, while the injection of H2 in the deposition chamber leads to the growth of hexagonal boron nitride (h-BN), H2 limiting the negative effect of bromide. The distance between the plasma source and the substrate has a strong influence on the films stoichiometry which partly explains why the h-BN layers are not stable with a fast deterioration into boric acid. [ABSTRACT FROM AUTHOR]

Objectives: Women are under-represented in the sports literature despite increasing rates of sports participation. Our objective was to investigate the risks and benefits of an elite women's soccer career in five health domains: general, musculoskeletal, reproductive endocrinology, post-concussion, and mental. Methods: An online survey was distributed to retired US college, semi-professional, professional, and national team soccer players using personal networks, email, and social media. Short validated questionnaires were used to evaluate the health domains, including the Patient-Reported Outcomes Measurement Information System (PROMIS), Single Assessment Numerical Evaluation (SANE), Post-Concussion Symptom Scale (PCSS), and Patient Health Questionnaire (PHQ). Results: A total of 560 eligible players responded to the survey over a 1-year period. The highest competitive levels were 73% college, 16% semi-professional, 8% professional, and 4% national team. The mean number of years since retirement was 12 (SD = 9), and 17.0% retired for involuntary reasons. The mean SANE scores (0–100 scale as percentage of normal) were knee = 75% (SD = 23), hip = 83% (SD = 23), and shoulder = 87% (SD = 21). The majority (63%) reported that their current activity level included participation in impact sports. A substantial proportion of players reported menstrual irregularities during their careers: 40% had fewer periods with increasing exercise and 22% had no periods for ≥ 3 months. The players (n = 44) who felt that post-concussion symptoms were due to soccer reported more time-loss concussions (F[2] = 6.80, p = 0.002) and symptom severity (F[2] = 30.26, p < 0.0001). Players who recently retired (0–5 years) reported the highest anxiety/depression scores and lowest satisfaction rates compared with those who retired 19+ years ago. Conclusion: Health concerns include musculoskeletal injuries, post-concussion symptoms, and lower mental health in the early years following retirement. This comprehensive survey provides initial results that will lay the foundation for further analyses and prioritize research studies that can help all female athletes. [ABSTRACT FROM AUTHOR]

Three-dimensional printing and casting materials were analyzed by prompt gamma-ray activation analysis (PGAA) to determine their suitability as human tissue surrogates for the fabrication of phantoms for medical imaging and radiation dosimetry applications. Measured elemental compositions and densities of five surrogate materials simulating soft tissue and bone were used to determine radiological properties (x-ray mass attenuation coefficient and electron stopping power). When compared with radiological properties of International Commission on Radiation Units and Measurements (ICRU) materials, it was determined that urethane rubber and PLA plastic yielded the best match for soft tissue, while silicone rubber and urethane resin best simulated the properties of bone. [ABSTRACT FROM AUTHOR]

Background: Women with endometrial or ovarian cancer experience a variety of symptoms during chemotherapy. Patient-Reported outcomes (PROs) can provide insight into the symptoms they experience. A PRO tool tailored to this patient population can help accurately monitor adverse events and manage symptoms. The objective of this study was to identify items in the National Cancer Institute's measurement system Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE®) appropriate for use in a PRO tool for a population of women with endometrial or ovarian cancer undergoing treatment with taxanes (paclitaxel or docetaxel) in combination with carboplatin. Methods: A two-phase, sequential multi-methods approach was applied. In phase one, a comprehensive literature search was done to map the toxicity of the applied chemotherapeutics and phase III clinical studies. Phase two, which comprised selecting the PRO-CTCAE items, included discussions with and feedback from a patient advisory board, an additional literature search, and focus group interviews with senior oncologists and specialized oncology nurses. A national expert panel facilitated both phases in terms of carefully select items from the PRO-CTCAE library. Results: Phase one identified 18 symptoms and phase two, three additional ones, leading to the inclusion of 21 PRO-CTCAE symptoms in the final PRO tool. Since PRO-CTCAE also contains one to three sub-questions on the frequency, severity, and interference with daily activities of symptoms, there were 44 potential items. Conclusions: This study describes taking a multi-method approach to selecting items from the PRO-CTCAE library for use in a population of women with endometrial or ovarian cancer undergoing chemotherapy. By systematically combining diverse approaches, we carefully selected 21 clinically relevant symptoms covered by 44 items in the PRO-CTCAE library. Future studies should investigate the psychometric properties of this PRO tool for women with endometrial or ovarian cancer. Plain English Summary: Women undergoing chemotherapy for endometrial or ovarian cancer experience a variety of symptoms and side effects associated with the disease and its treatment. One way to strengthen patient involvement during the treatment trajectory is to use patient-reported outcomes (PROs). Since PROs represent the patient's response to inquiries about their current level of health, they should be tailored to the specific disease. As a result, we developed a PRO tool that targets women undergoing chemotherapy for endometrial or ovarian cancer. We conducted a comprehensive literature search and used various methods to map symptoms and side effects. Furthermore, discussions with and feedback from a patient advisory board, focus group interviews with oncologists and specialized oncology nurses, and advice from a gynecological national expert panel that we established helped us determine which symptoms a PRO tool for this patient group should include. This led to the inclusion of 21 symptoms in the final PRO tool, which is currently being tested. The selection process we applied may be generalizable for use in selecting PROs for other cancer populations. [ABSTRACT FROM AUTHOR]

It has been proposed that representations emerge from a single memory system organized along a continuum of specificity. This continuum is assumed to reflect a scale between the simulation of overlapping and specific features of the traces, which depends on trace distinctiveness. More specifically, higher trace distinctiveness facilitates the simulation of trace-specific features, which increase the discriminability of traces and lead to the emergence of a more specific representation. In two experiments, participants were asked to identify match (low task discrimination demand) or mismatch (high task discrimination demand) associations between actions and characters that were visually either highly or lowly distinctive. The results of Experiment 1 show that in the high-distinctiveness context, performance was better when identifying a mismatch rather than a match, while the opposite was true in the low-distinctiveness context. The results of Experiment 2 show that using a dynamic visual noise to interfere with the participants' ability to simulate the features of the characters also reduced the benefit of the high-distinctiveness context for the mismatch trials (Experiment 2a and 2b) and increased the benefit of the low-distinctiveness context for the match trials (Experiment 2b). Taken together, these results suggest that the simulation of trace-specific features underlies the emergence of specific representations, which can be beneficial when the discrimination demand of the task is high and detrimental when this demand is low. Memory might therefore be viewed as a scale of simulation between overlapping and specific trace features. [ABSTRACT FROM AUTHOR]

Heart failure is a highly morbid syndrome, recognized as a major cause of adult mortality. Heart failure in pediatric patients, whether in the setting of congenital or acquired heart disease, is similarly associated with high mortality and resource utilization. Understanding the clinical presentation, diagnosis, and initial stabilization of pediatric heart failure is paramount for any acute care clinician as it may mimic common childhood ailments like viral respiratory or gastrointestinal illnesses. Pediatric heart failure occurs in patients with palliated or unpalliated congenital heart disease, familial or acquired cardiomyopathy, acquired valve disease, and myocarditis. This review will focus on heart failure in pediatric patients with structurally normal hearts and will summarize what is known about patterns of presentation, etiologies, diagnostic evaluation, and the acute and chronic management of this highly morbid syndrome. [ABSTRACT FROM AUTHOR]

The sustainable development goals (SDGs) constitute an ambitious comprehensive global framework including monitoring mechanisms and indicators to evaluate progress towards precise targets of sustainable development. Most European countries have adapted their national sustainability indicator systems to conform to the UN Agenda 2030 for sustainable development, introducing new indicators and monitoring frameworks and governance processes in which these are embedded. What do we know about the political processes and struggles of implementing this important global framework? How does the politics of indicators differ in national contexts? We propose a classification of national indicator systems along dimensions of indicator selection, appraisal landscape, participatory nature, and political communication. We empirically explore these dimensions for four European national sustainability indicator systems through a comparative analysis based on national policy documents, indicator databases, and web portals as well as inputs from workshops and expert interviews. Given the considerable variation with respect to the trajectory of national sustainability indicator systems, we posit that these differences correspond to different national interpretations of sustainability. [ABSTRACT FROM AUTHOR]

The United Nations 2030 Agenda and Sustainable Development Goals (SDGs) define a path towards a sustainable future, but given that uncertainty characterises the outcomes of any SDG-related actions, risks in the implementation of the Agenda need to be addressed. At the same time, most risk assessments are narrowed to sectoral approaches and do not refer to SDGs. Here, on the basis of a literature review and workshops, it is analysed how SDGs and risks relate to each other's in different communities. Then, it is formally demonstrated that, as soon as the mathematical definition of risks is broadened to embrace a more systemic perspective, acting to maintain socio-environmental systems within their sustainability domain can be done by risk minimisation. This makes Sustainable Development Goals and risks "the Yin and the Yang of the paths towards sustainability". Eventually, the usefulness of the SDG-risk nexus for both sustainability and risk management is emphasized. [ABSTRACT FROM AUTHOR]

This article is based on 9 months of ethnographic fieldwork carried out in Cairo, Egypt during the years of 2015 and 2017 as part of a research project on the topic of type-2 diabetes. The article examines different understandings of the onset and treatment of type-2 diabetes across people in Cairo living with the condition and their healthcare providers. The article argues that those who are diagnosed with type-2 diabetes primarily relate their condition to experiences of ḍaghṭ (stress or pressure), above any other risk factors. This understanding clashes with healthcare providers who instead link type-2 diabetes primarily to obesity. The article exemplifies these different understandings of type-2 diabetes by drawing on the topic of food specifically, showing how the intake of food is not perceived by those diagnosed with type-2 diabetes as related to their condition in similar ways as is the case among their healthcare providers. As opposed to relating type-2 diabetes to matters of abundance and an excess consumption of food and calories, those in Cairo who are diagnosed with type-2 diabetes instead relate their condition to matters of deprivation and scarcity—as well as the experiences of ḍaghṭ brought on by such potential deprivation and scarcity. [ABSTRACT FROM AUTHOR]

The little fire ant, Wasmannia auropunctata, is an invasive species known to negatively affect many native species in its introduced range. Here, we studied the effect of little fire ant presence on the biomass of soil fauna in rainforest of New Caledonia to assess if little fire ants have an impact on an endangered endemic flightless bird, the kagu, Rhynochetos jubatus. The average biomass of soil fauna (except for millipedes) was lower in 53 sample plots with little fire ants than in 597 sample plots without little fire ants and the biomass decreased with increasing density of little fire ant nests. Millipedes on the contrary seemed to be positively impacted as their average biomass was higher in areas with fire ants than in areas without, but even millipede biomass decreased with increasing nest density of fire ants. Kagu density decreased with increasing area of rainforest invaded by little fire ants, suggesting, given their observed negative impact on soil fauna biomass, that they may limit food resources for kagu. Little fire ants might therefore transform rainforest into a less suitable habitat for the kagu by reducing the biomass of their prey and thus have a negative impact for kagu conservation. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) is associated with atypical neural activity in resting state. Most of the studies have focused on abnormalities in alpha frequency as a marker of ASD dysfunctions. However, few have explored alpha synchronization within a specific interest in resting-state networks, namely the default mode network (DMN), the sensorimotor network (SMN), and the dorsal attention network (DAN). These functional connectivity analyses provide relevant insight into the neurophysiological correlates of multimodal integration in ASD. Methods: Using high temporal resolution EEG, the present study investigates the functional connectivity in the alpha band within and between the DMN, SMN, and the DAN. We examined eyes-closed EEG alpha lagged phase synchronization, using standardized low-resolution brain electromagnetic tomography (sLORETA) in 29 participants with ASD and 38 developing (TD) controls (age, sex, and IQ matched). Results: We observed reduced functional connectivity in the ASD group relative to TD controls, within and between the DMN, the SMN, and the DAN. We identified three hubs of dysconnectivity in ASD: the posterior cingulate cortex, the precuneus, and the medial frontal gyrus. These three regions also presented decreased current source density in the alpha band. Conclusion: These results shed light on possible multimodal integration impairments affecting the communication between bottom-up and top-down information. The observed hypoconnectivity between the DMN, SMN, and DAN could also be related to difficulties in switching between externally oriented attention and internally oriented thoughts. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) is associated with atypical neural activity in resting state. Most of the studies have focused on abnormalities in alpha frequency as a marker of ASD dysfunctions. However, few have explored alpha synchronization within a specific interest in resting-state networks, namely the default mode network (DMN), the sensorimotor network (SMN), and the dorsal attention network (DAN). These functional connectivity analyses provide relevant insight into the neurophysiological correlates of multimodal integration in ASD. Methods: Using high temporal resolution EEG, the present study investigates the functional connectivity in the alpha band within and between the DMN, SMN, and the DAN. We examined eyes-closed EEG alpha lagged phase synchronization, using standardized low-resolution brain electromagnetic tomography (sLORETA) in 29 participants with ASD and 38 developing (TD) controls (age, sex, and IQ matched). Results: We observed reduced functional connectivity in the ASD group relative to TD controls, within and between the DMN, the SMN, and the DAN. We identified three hubs of dysconnectivity in ASD: the posterior cingulate cortex, the precuneus, and the medial frontal gyrus. These three regions also presented decreased current source density in the alpha band. Conclusion: These results shed light on possible multimodal integration impairments affecting the communication between bottom-up and top-down information. The observed hypoconnectivity between the DMN, SMN, and DAN could also be related to difficulties in switching between externally oriented attention and internally oriented thoughts. [ABSTRACT FROM AUTHOR]

Growth and environmental responses are essential for living organisms to survive and adapt to constantly changing environments. In order to simulate new conditions and capture dynamic responses to environmental shifts in a developing whole-cell model of E. coli, we incorporated additional regulation, including dynamics of the global regulator guanosine tetraphosphate (ppGpp), along with dynamics of amino acid biosynthesis and translation. With the model, we show that under perturbed ppGpp conditions, small molecule feedback inhibition pathways, in addition to regulation of expression, play a role in ppGpp regulation of growth. We also found that simulations with dysregulated amino acid synthesis pathways provide average amino acid concentration predictions that are comparable to experimental results but on the single-cell level, concentrations unexpectedly show regular fluctuations. Additionally, during both an upshift and downshift in nutrient availability, the simulated cell responds similarly with a transient increase in the mRNA:rRNA ratio. This additional simulation functionality should support a variety of new applications and expansions of the E. coli Whole-Cell Modeling Project. [ABSTRACT FROM AUTHOR]

Magnetic skyrmions are topological spin textures that hold great promise as nanoscale information carriers in non-volatile memory and logic devices. While room-temperature magnetic skyrmions and their current-induced motion were recently demonstrated, the stray field resulting from their finite magnetisation and their topological charge limit their minimum size and reliable motion. Antiferromagnetic skyrmions allow to lift these limitations owing to their vanishing magnetisation and net zero topological charge, promising ultra-small and ultra-fast skyrmions. Here, we report on the observation of isolated skyrmions in compensated synthetic antiferromagnets at zero field and room temperature using X-ray magnetic microscopy. Micromagnetic simulations and an analytical model confirm the chiral antiferromagnetic nature of these skyrmions and allow the identification of the physical mechanisms controlling their size and stability. Finally, we demonstrate the nucleation of synthetic antiferromagnetic skyrmions via local current injection and ultra-fast laser excitation. Skyrmions in synthetic antiferromagnets are appealing for use in future memory and computing devices, combining small size and fast motion, but creating, stabilizing, and observing them remains a challenge. Here, Juge et al demonstrate the stabilization and current and light induced nucleation of skyrmions in a synthetic antiferromagnet, observing the magnetization texture in each layer using X-ray magnetic microscopy. [ABSTRACT FROM AUTHOR]

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The use of biomimetic models of the glomerulus has the potential to improve our understanding of the pathogenesis of kidney diseases and to enable progress in therapeutics. Current in vitro models comprise organ-on-a-chip, scaffold-based and organoid approaches. Glomerulus-on-a-chip designs mimic components of glomerular microfluidic flow but lack the inherent complexity of the glomerular filtration barrier. Scaffold-based 3D culture systems and organoids provide greater microenvironmental complexity but do not replicate fluid flows and dynamic responses to fluidic stimuli. As the available models do not accurately model the structure or filtration function of the glomerulus, their applications are limited. An optimal approach to glomerular modelling is yet to be developed, but the field will probably benefit from advances in biofabrication techniques. In particular, 3D bioprinting technologies could enable the fabrication of constructs that recapitulate the complex structure of the glomerulus and the glomerular filtration barrier. The next generation of in vitro glomerular models must be suitable for high(er)-content or/and high(er)-throughput screening to enable continuous and systematic monitoring. Moreover, coupling of glomerular or kidney models with those of other organs is a promising approach to enable modelling of partial or full-body responses to drugs and prediction of therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Due to the first COVID-19 outbreak and subsequent restrictions, standard practice for gynecological cancer quickly evolved to include additional digital consultations. Women with gynecological cancer have a high need for information and experience a high symptom burden. We aimed to explore the experiences and perspectives of the rapid implementation of digital consultations during COVID-19. Methods: We conducted individual telephone interviews with patients with gynecological cancer 1–4 days after a telephone or video consultation during the COVID-19 outbreak in April and May 2020. We applied Braun and Clarke's thematic analysis to analyze the qualitative data. Results: Thirty-two patients with ovarian (50%), cervical (35%), vulvar (12%), and vaginal cancer (3%) participated in the study. The patients experienced that, combined, cancer and COVID-19 restrictions made their situation twice as challenging. In general, the patients valued face-to-face consultations, recommending that they were ideal for the initial appointment to build trust. Overall, there was a willingness to participate in digital consultations because of the restrictions, but the results also showed varying degrees of openness and that individual solutions were favored. Conclusion: The findings of this study show that digital consultations were an accepted alternative during COVID-19. Even though this temporary solution was deemed to be beneficial for practical reasons, patients also experienced digital consultations to be impersonal. A key message is that face–to–face encounters create the foundation to establish a trusting relationship from where a valuable dialogue arises. Digital consultations should therefore be implemented with caution since no one-size-fits-all model is recommended. Among patients with gynecological cancer, however, digital technologies represent a promising and flexible method depending on the purpose of consultations, patient preferences, and needs. [ABSTRACT FROM AUTHOR]

Characteristics of persistent post-traumatic headache (PTH) in young individuals are poorly known leading to diagnostic problems and diverse management. We aimed to describe headache phenotypes and self-reported management strategies in young individuals with PTH following mild traumatic brain injury (mTBI). A comprehensive structured questionnaire was used to evaluate headache phenotypes/characteristics and management strategies to relieve headache in 107, 15–30-year-old individuals with PTH. Around 4 months post-injury, migraine-like headache in combination with tension-type like headache (40%) was the most commonly encountered headache phenotype followed by migraine-like headache (36%). Around 50% reported aura-like symptoms before/during the headache attack. Medication-overuse headache was diagnosed in 10%. Stress, sleep disturbances, and bright lights were the most common trigger factors. More than 80% reported that their headache was worsened by work-related activity and alleviated by rest/lying down. Simple analgesics were commonly used (88%) whereas prophylactic drugs were rarely used (5%). Bedrest and physiotherapy were also commonly used as management strategies by 56% and 34% of the participants, respectively. In conclusion, most young individuals with PTH after mTBI presented with combined migraine-like and tension-type-like headache followed by migraine-like headache, only. Preventive headache medication was rarely used, while simple analgesics and bedrest were commonly used for short-term headache relief. [ABSTRACT FROM AUTHOR]

The lower basin of Coatzacoalcos River is one of the most polluted regions of the southern Gulf of Mexico. Organochlorine compounds, polybrominated diphenyl ethers, polycyclic aromatic hydrocarbons, and heavy metals have been registered in this region. In the present study, genotoxicity was evaluated in the blood of giant toads (Rhinella marina) from Coatzacoalcos' rural and industrial zones, and compared with laboratory toads. Determination of the frequency of micronucleus and erythrocyte nuclear abnormalities by the light microscope and cell cycle and apoptosis by flow cytometry were used as biomarkers of genotoxicity. We found more variability in micronucleus and more nuclear buds in toads from industrial zones. Also, cell cycle alterations and an increase of apoptosis in erythrocytes were found in toads from rural and industrial zones. Multivariate statistics show that the toads from the industrial zone were more affected than toads from laboratory and rural zones. [ABSTRACT FROM AUTHOR]

Background: Iron deficiency and hepatic steatosis are common in bariatric surgery patients. Steatosis can falsely elevate ferritin values even in presence of iron deficiency. This study aims to assess the influence of hepatic steatosis on iron deficiency and replacement therapy after bariatric surgery. Methods: Seventy-nine individuals undergoing gastric bypass have been studied at 4 time points (preoperative and 1, 3, and 6 months after surgery). Weight, body mass index (BMI), iron, ferritin, vitamin B12, folate, hemoglobin, gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and use of iron replacement were recorded. Results: Forty-two individuals (53%) had moderate/severe steatosis assessed by ultrasound. No differences were seen in iron profile and replacement therapy features compared to individuals with no/mild steatosis both in the preoperative and postoperative periods. Mixed model analysis showed ferritin levels to be higher in the moderate/severe steatosis group than in no/mild steatosis at the 6th month (139 ± 131 vs. 60.9 ± 49.8, p < 0.05). Values in both groups were lower than baseline, with p < 0.0001. The same was observed with serum iron (92.1 ± 39.6 moderate/severe steatosis vs. 68.6 ± 33.4 no/mild steatosis, p < 0.001; p from baseline < 0.01 for both). GGT was higher in moderate/severe steatosis in the 3rd month (38.8 ± 40.5 vs. 28.8 ± 20.8, p < 0.05; p from baseline < 0.0001 for both). Conclusions: Ferritin levels were consistently higher in individuals with steatosis in the follow-up of bariatric surgery, but no apparent implication on the diagnosis of iron deficiency and in the prescription of replacement therapy was demonstrated at 6 months of follow-up. Longer studies are probably necessary to investigate this matter. [ABSTRACT FROM AUTHOR]

Purpose: High plasma vitamin D (VitD) level and regular exercise (Ex) are known to have anti-cancer and immunomodulatory effects. This study aimed to evaluate the impact of VitD supplementation and imposed physical Ex on mammary tumour growth and immune response in ovariectomised mice fed high-fat (HF) diet. Methods: Ovariectomised 33-week-old mice C57BL/6 (n = 60), housed in enriched environment (EE), were fed HF diet (450 kcal/100 g) supplemented or not with VitD (HF/HF + D: 125/1225 IU/100 g) for 12 weeks and submitted or not to Ex (HF + Ex; HF + D + Ex) on treadmill (45 min/day, 5 days/week). At w8, syngeneic tumour cells EO771 were orthotopically injected into the 4th mammary gland. Spontaneous activity (SPA), maximal speed (MS) and forelimb grip strength (GS) were measured. Tumour immune cells infiltrate was phenotyped by FACS. Data (mean ± SEM) were analysed by two-way ANOVA + Tukey post-test. Results: Ex (p = 0.01) and VitD (p = 0.05) reduced body weight gain. Exercise decreased visceral fat mass [g: 1.5 ± 0.8 (HF); 1.2 ± 0.65 (HF + Ex); 0.9 ± 0.6 (HF + D + Ex); p = 0.03]. SPA (p < 0.0001) and GS (p = 0.01) were higher in HF + D + Ex mice vs others. No effect of Ex or VitD on tumour growth was detected. In tumour, VitD decreased the proportion of NK (p = 0.03), while Ex increased it (p = 0.03). The Th1/Th2 ratio is lowered by VitD (p = 0.05), while Tc/Treg ratio was not affected either by Exercise or VitD. Conclusion: In our experimental conditions, VitD supplementation and physical exercise have synergetic effects reducing the weight gain under HF diet and improving the physical capacities of mice. VitD coupled with exercise induces an immunosuppressive response without effect on tumour growth. [ABSTRACT FROM AUTHOR]

Background: Applied tube voltage (kilovolts, kV) and tube current (milliampere seconds, mAs) affect CT radiation dose and image quality and should be optimised for the individual patient. CARE kV determines the kV and mAs providing the lowest dose to the patient, whilst maintaining user-defined reference image quality. Given that kV changes affect CT values which are used to obtain attenuation maps, the aim was to evaluate the effect of kV changes on PET quantification and CT radiation dose using phantoms. Method: Four phantoms ('Lungman', 'Lungman plus fat', 'Esser' and 'NEMA image quality' (NEMA IQ)) containing F-18 sources underwent 1 PET and 5 CT scans, with CARE kV on (automatic kV selection and mAs modulation) and in semi mode with specified tube voltages of 140, 120, 100 and 80 kV (mAs modulation only). A CARE kV image quality reference of 120 kV/50 mAs was used. Impact on PET quantification was determined by comparing measured activity concentrations for PET reconstructions from different CT scans with the reconstruction using the 120 kV reference, and dose (DLP, CTDIvol) differences calculated by comparing doses from all kV settings with the 120 kV reference. Results: CARE kV-determined optimal tube voltage and CARE kV 'on' dose (DLP) savings compared with the 120 kV reference were: Lungman, 100 kV, 2.0%; Lungman plus fat, 120 kV, 0%; Esser, 100 kV, 9.3%; NEMA IQ, 100 kV, 3.4%. Using tube voltages in CARE kV 'semi' mode which were not advised by CARE kV 'on' resulted in dose increases ≤ 65% compared with the 120 kV reference (greatest difference Lungman plus fat, 80 kV). Clinically insignificant differences in PET activity quantification of up to 0.7% (Lungman, 100 kV, mean measured activity concentration) were observed when using the optimal tube voltage advised by CARE kV. Differences in PET quantification of up to 4.0% (Lungman, 140 kV, maximum measured activity concentration) were found over the full selection of tube voltages in semi mode, with the greatest differences seen at the most suboptimal kV for each phantom. However, most differences were within 1%. Conclusions: CARE kV on can provide CT radiation dose savings without concern over changes in PET quantification. [ABSTRACT FROM AUTHOR]

The potentially fatal cardiovascular effects of hypoglycaemia are not well understood and large animal models of the counter-regulatory responses and cardiovascular consequences of insulin-induced hypoglycaemia are needed to understand the mechanisms in humans. The aim of this study was to develop a human-like minipig model of hypoglycaemia including healthy and diabetic pigs to investigate endocrine, electrocardiographic and platelet effects. Hypoglycaemia was induced using a hyperinsulinaemic, hypoglycaemic clamp and an insulin bolus protocol. Plasma glucose, glucagon, C-peptide, insulin, epinephrine and platelet aggregation responses were measured before, during and after hypoglycaemia. Continuous electrocardiographic recordings were obtained. Hypoglycaemia at a plasma glucose concentration of 0.8–1.0 mM in the clamp induced 25-fold increase in epinephrine and sixfold and threefold increase in glucagon for healthy and diabetic pigs, respectively. The hypoglycaemic clamp induced QTc-interval prolongation and increase in cardiac arrhythmias. In the bolus approach, the non-diabetic group reached plasma glucose target of 1.5 mM and QTc-interval was prolonged after insulin injection, but before glucose nadir. The diabetic group did not reach hypoglycaemic target, but still demonstrated QTc-interval prolongation. These results demonstrate effects of hyperinsulinaemic hypoglycaemia closely resembling human physiology, indicating the minipig as a translational animal model of counter-regulatory endocrine and myocardial effects of hypoglycaemia. [ABSTRACT FROM AUTHOR]

Socioeconomic status (SES) is inversely associated with risks of type 2 diabetes (T2D). We investigated if young men's cognitive function, measured by intelligence test scores and educational level, as determinants of SES modified associations between body mass index (BMI) and height with the risk of T2D. 369 989 young men from the Danish Conscription Database born between 1939 and 1959 with information on measured height, weight, intelligence test scores, and education were linked to the Danish National Patient Register. During follow-up from 1977 through 2015, T2D was recorded in 32 188 men. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox regressions. BMIs below-average (z-scores ≤ 0) were not related to risks of T2D. For BMIs above-average (z-scores > 0), positive associations between BMI and T2D were slightly stronger among men with higher intelligence test scores or longer educations than among men with lower levels of these factors (pinteraction-values < 0.004). Irrespective of BMI, incidence rates of T2D were higher among men with low levels of intelligence test score and education. Height was inversely associated with T2D (per z-score, HR = 0.96 (95% CI 0.95–0.97) and the association did not vary by intelligence test scores or education (all pinteraction-values > 0.59). While below-average BMI was not associated with T2D risk, above-average BMIs were and these association were stronger among men with high cognitive function. Nevertheless, T2D risk was higher at lower levels of cognitive function throughout the range of BMI. Height was inversely associated with T2D and it was not modified by cognitive function. [ABSTRACT FROM AUTHOR]

Purpose: Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA0,TYR3-octreotate ([177Lu]Lu-DOTA-TATE) and the mechanistic target of rapamycin (mTOR) inhibitor everolimus are both approved for the treatment of neuroendocrine tumours (NET). However, tumour progression is still frequent, and treatment strategies need further improvement. One possible approach could be to combine different therapy options. In this study, we investigated the toxicity of a combined treatment with everolimus and [177Lu]Lu-DOTA-TATE in female Lewis rats. Methods: Animals received 200 MBq of [177Lu]Lu-DOTA-TATE once and/or 5 mg/kg body weight everolimus or placebo weekly for 16 weeks and were divided into four groups (group 1, placebo; group 2, everolimus; group 3, placebo + [177Lu]Lu-DOTA-TATE; group 4, everolimus + [177Lu]Lu-DOTA-TATE). Blood levels of creatinine and blood urea nitrogen (BUN) were assessed weekly to monitor nephrotoxicity, and a full blood count was performed at the time of euthanasia to monitor myelotoxicity. Additionally, renal function was analysed by sequential [99mTc]Tc-mercaptoacetyltriglycine ([99mTc]Tc-MAG3) scintigraphies. Histopathological examination was performed in all the kidneys using a standardized renal damage score (RDS). Results: Rats receiving everolimus showed a significantly lower increase in creatinine levels than those receiving placebo. Everolimus therapy reduced white blood count significantly, which was not observed for [177Lu]Lu-DOTA-TATE. Functional renal scintigraphies using [99mTc]Tc-MAG3 showed a compromised initial tracer uptake after PRRT and slower but still preserved excretion after everolimus. Histology showed no significant RDS differences between groups. Conclusion: Renal scintigraphy is a highly sensitive tool for the detection of renal function impairment after a combination of everolimus and PRRT. Additional treatment with everolimus does not increase renal and haematological toxicity of PRRT with [177Lu]Lu-DOTA-TATE. [ABSTRACT FROM AUTHOR]

Patient-specific 3D modeling is the first step towards image-guided surgery, the actual revolution in surgical care. Pediatric and adolescent patients with rare tumors and malformations should highly benefit from these latest technological innovations, allowing personalized tailored surgery. This study focused on the pelvic region, located at the crossroads of the urinary, digestive, and genital channels with important vascular and nervous structures. The aim of this study was to evaluate the performances of different software tools to obtain patient-specific 3D models, through segmentation of magnetic resonance images (MRI), the reference for pediatric pelvis examination. Twelve software tools freely available on the Internet and two commercial software tools were evaluated using T2-w MRI and diffusion-weighted MRI images. The software tools were rated according to eight criteria, evaluated by three different users: automatization degree, segmentation time, usability, 3D visualization, presence of image registration tools, tractography tools, supported OS, and potential extension (i.e., plugins). A ranking of software tools for 3D modeling of MRI medical images, according to the set of predefined criteria, was given. This ranking allowed us to elaborate guidelines for the choice of software tools for pelvic surgical planning in pediatric patients. The best-ranked software tools were Myrian Studio, ITK-SNAP, and 3D Slicer, the latter being especially appropriate if nerve fibers should be included in the 3D patient model. To conclude, this study proposed a comprehensive review of software tools for 3D modeling of the pelvis according to a set of eight criteria and delivered specific conclusions for pediatric and adolescent patients that can be directly applied to clinical practice. [ABSTRACT FROM AUTHOR]

Females of the Queensland fruit fly (QFF), Bactrocera tryoni, are amongst the most damaging pests of horticulture in Australia and neighboring countries. Females can lay eggs into more than a hundred species of fruits and vegetables, resulting in large crop losses. Sexually mature males can be managed sustainably with traps baited with long-lasting synthetic lures, and sexually immature males and females can be attracted and killed by short-lived protein baits applied directly on surfaces, with a low success rate (< 20%). No long-lasting attractants for virgin or mated females exist. With the aim of developing a female attractant for surveillance, we collected and analyzed the odors of four ripe host fruits: orange, cherry guava, banana and feijoa. Virgin and mated female QFF were tested with gas-chromatography coupled with electro-antennographic detection to identify electrophysiologically (EAD)-active compounds. We detected 41 EAD-active compounds, with seven found common for more than one fruit. Overall, mated females responded more often and with higher intensity than virgin females. In particular, five compounds present either in cherry guava or feijoa triggered a significantly higher EAD response from mated females than from virgins. Twenty-six EAD-active compounds were selected and tested individually in a Y-tube olfactometer to measure attraction of both virgin and mated females. Behavioral responses differed significantly amongst the compounds, but not strongly between virgin and mated females. We did not find any correlation between electrophysiological and behavioral responses. Further field testing with behaviorally-active compounds is needed for the development of a new QFF female lure. [ABSTRACT FROM AUTHOR]

Purpose: There are limited data regarding subclinical atherosclerosis in Middle Eastern countries. We aimed to describe and compare coronary computed tomographic angiography (CCTA) findings in Qatari native and South Asian migrants at increased risk of coronary artery disease (CAD).Methods: We performed CCTA in 251 consecutive volunteers (126 South Asian, 125 Qatari, mean age 50.0 ± 7.3 years, 27.1% female) at increased risk of cardiovascular disease. Given differences in baseline risk factors, we employed propensity score matching to create a cohort of 162 subjects for comparative analyses. We compared CAD severity, extent, plaque morphology, adverse plaque characteristics, and quantitative measures of atherosclerotic burden in both subgroups.Results: After matching, no CAD was seen in 58.0% of South Asians and 49.4% of Qataris (p = 0.3), while obstructive CAD (≥50% luminal stenosis) was present in 40.7% of South Asians and 49.4% of Qataris (p = 0.3). There was a high prevalence of adverse plaque characteristics in both ethnicities, particularly positive remodeling. South Asians had significantly smaller vessel and lumen volumes, but the percent aggregate plaque volumes were not significantly different (2.9 ± 6.3% vs. 3.8 ± 8.0%, p = 0.4).Conclusions: In this first study of CCTA findings performed in a Middle Eastern country, we observed a high prevalence of obstructive CAD in a middle-aged cohort. There were no significant differences in CCTA findings between Qataris and South Asians after adjustment for clinical risk factors. Future studies are needed to identify patterns of coronary atherosclerosis by CCTA in non-European populations where cardiovascular disease is increasingly prevalent. [ABSTRACT FROM AUTHOR]

Key summary points: Aim: To assess the prevalence of inappropriate prescriptions of antithrombotic therapies (AT) in older outpatients, and to examine the associated factors. Findings: 22.6% patients featured ≥ 1 in AT-STOPP criteria, 12.4% ≥ 1 in AT-START criteria. The most frequent AT-STOPP criterion was AT prescription despite a concurrent significant bleeding risk. The most frequent AT-START criterion was lack of AT prescription for patients with chronic atrial fibrillation. Two factors were associated with ≥ 1 AT-STOPP criteria: polymedication and previous hospitalization for a serious adverse drug event. The only factor associated with ≥ 1 AT-START criteria was lack of information in the prescription regarding the duration of treatment. Message: Suboptimal prescribing of AT is common in GP's prescriptions for older autonomous outpatients. Special attention should be given to those with polymedication and a history of severe adverse drug event. Purpose: To assess the prevalence of inappropriate prescriptions of antithrombotic therapies (AT) in older outpatients and examine the associated factors. Methods: A multicenter cross-sectional study was performed in 75 community pharmacies of 11 French districts. The study included 1178 patients aged ≥ 75 years filling a prescription from a general practitioner (GP) at a community pharmacy (mean [SD] age 83 [± 5.5] years, 59% female, median prescribed drugs 7 [range 5–10]).75 pharmacy students prospectively collected data from structured interviews with patients and from prescriptions into an electronic case report. Updated 2014 STOPP/START criteria regarding AT were applied to each prescription. Factors associated with ≥ 1 AT-STOPP criteria and ≥ 1 AT-START criteria were studied (multivariate analysis). Results: 22.6% patients featured ≥ 1 in AT-STOPP criteria and 12.4% ≥ 1 in AT-START criteria. The most frequent AT-STOPP and AT-START criteria were AT prescription despite a concurrent significant bleeding risk and lack of AT prescription for patients with chronic atrial fibrillation, respectively. Two factors were associated with ≥ 1 AT-STOPP criteria: polymedication (≥ 5 drugs; p < 0.001) and previous hospitalization for a serious adverse drug event (ADE; p = 0.007). The only factor associated with ≥ 1 AT-START criteria was lack of information in the prescription regarding the duration of treatment. Conclusion: Suboptimal prescribing of AT is common in GP's prescriptions for older autonomous outpatients. The currently process of prescribing AT to older autonomous patients must be improved. Special attention should be given to those with polymedication and those with a history of severe ADEs. [ABSTRACT FROM AUTHOR]

Among the various existing and mathematically equivalent definitions of the skeleton, we consider the set of critical points of the Euclidean distance transform of the shape. The problem of detecting these points and using them to generate a skeleton that is stable, thin and homotopic to the shape has been the focus of numerous papers. Skeleton branches correspond to ridges of the distance map, i.e., continuous lines of points that are local maxima of the distance in at least one direction. Extracting these ridges is a non-trivial task on a discrete grid. In this context, the average outward flux, used in the Hamilton-Jacobi skeleton (Siddiqi et al. in Int J Comput Vis 48(3):215-231, 2002), and the ridgeness measure (Leborgne et al. in J Vis Commun Image Represent 31:165-176, 2015) have been proposed as ridge detectors. We establish the mathematical relation between these detectors and, extending the work in Dimitrov et al. (Computer vision and pattern recognition, pp 835-841, 2003), we study various local shape configurations, on which closed-form expressions or approximations of the average outward flux and ridgeness can be derived. In addition, we conduct experiments to assess the accuracy of skeletons generated using these measures and study the influence of their respective parameters. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "The Women's Soccer Health Study: From Head to Toe" which appeared in the May 31, 2023 issue.

Although learning indicators are now properly studied and published, it is still very difficult to manage them freely within most distance learning platforms. As all activity indicators need to collect and analyze properly traces of the learning activity, we propose to use these traces as a starting point for a platform independent Trace Based-Indicator Management System (TB-IMS). This approach allows learning indicators to be created and reused in such a way that there is no need to modify the computer code of the learning platform. This paper presents the underlying theory and how this theory is implemented in a first TB-IMS. This TB-IMS is illustrated through an actual learning situation based on a Moodle platform. This approach is compared with similar attempts to manage learning indicators properly and is available for use with any other learning platform, provided the TB-IMS can access the learning platform traces. [ABSTRACT FROM AUTHOR]

Background In order to ensure safer prescriptions in the elderly, lists of potentially inappropriate medications (PIMs) and guidelines have been introduced. Whereas the effectiveness of these measures has been well studied in hospitals, data are sparse for the community-dwelling patients. Objective To assess the quality of prescriptions among community-dwelling elderly patients, and potential associations between prescription patterns, patient characteristics and medication adherence. Setting Community pharmacies in France. Method We conducted a prospective observational study between January and June 2013. Patients aged 75 and over coming to the community pharmacy with a prescription from a general practitioner were invited to participate to the study. The compliance of the prescription was assessed with regards to Beers Criteria and French Health Authority guidelines (FHA) for prescription in the elderly, the degree of adherence was assessed with the Girerd score. Main outcome measure Percentage of prescriptions compliant with Beers Criteria and FHA guidelines. Results Among the 1206 prescriptions analysed, 67.49% (n = 814) contained a PIM. Only 12.77% (n = 154) complied with mandatory requirements of the FHA. Prescriptions were ordered by therapeutic field in 51.24% (n = 618) of cases. Dosing regimen was incomplete in 57.21% (n = 690) of prescriptions. Only 29.19% (n = 352) of patients reported no difficulty with regard to adherence (Girerd score = 0). The use of International Non-proprietary Name was associated with an increased risk of nonadherence (adjusted OR = 1.59 [95% CI = 1.13-2.23] and 1.68 [95% CI = 1.12-2.49] respectively). Patient satisfaction with formulation was associated with a lower risk of non-adherence (adjusted OR = 0.63 [95% CI = 0.45-0.90]). Conclusion A substantial proportion of patients are exposed to PIMs and prescriptions that do not comply with the FHA Guidelines. This issue, as well as identified risk factors for non-adherence, should be taken into consideration by general practitioners and community pharmacists when prescribing/dispensing medications to the elderly. [ABSTRACT FROM AUTHOR]

Purpose of Review: The purpose of this paper is to identify strategies for a successful transition to sports in patients following rehabilitation for ACL reconstruction surgery (ACLR). Recent Findings: Recent research continues to demonstrate a relatively low rate of return to previous level of play among athletes following ACLR combined with a significant risk of injury to either the ipsi or the contralateral ACL. Recent research also demonstrates a growing use of a varied battery of assessments to determine readiness to return to sport as well as a lack of consensus on the ideal rehabilitation program, the criteria for clearance for return to play (both in time from surgery and functional milestones), and the nature of a conditioning program designed specifically for transitioning the cleared athlete back to competition. Summary: Due to the lack of consensus and consistency regarding rehabilitation protocols and criteria for clearance to play after ACLR, deficits in strength, neuromuscular control, and psychological readiness may exist in 'cleared' athletes. These deficits may not only negatively impact sports performance but also raise the risk of re-injury. Programs designed to successfully return an athlete to previous level of play should include not only strength and conditioning aimed at restoring fitness that was compromised as a result of the injury but also include attention to psychological readiness and address deficits in neuromuscular control. Problems that exist following ACLR cannot be solved by one professional; successful rehabilitation and return to play require a coordinated effort among the surgeon, physical therapist, athletic trainer, and fitness professional. Future research is needed to determine the optimal strategy to restore the neuromuscular control, functional strength, and psychological readiness necessary for a successful return to competition following ACLR. [ABSTRACT FROM AUTHOR]

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A simple and rapid focused ultrasound extraction method was developed for the determination of Persistent Organic Pollutants (POPs) in liver tissue obtained of giant toad ( Rhinella marina) using a gas chromatography coupled to a mass detector with electron impact ionization. The performed method for POPs, was validated in fortified matrix, showing linearity from the LOQ up to 100 ng/mL; LODs and LOQs for each compound were between 1.7 and 4.8 and 3.5-7.5 ng/mL, respectively. Recovery rates were among 79%-116% for POPs determined. Finally, the method was applied in liver samples of giant toads found in a malarial area in Mexico. The sensitivity of the proposed method was good enough to ensure reliable determination of target analytes at concentration levels commonly found in this kind of samples. [ABSTRACT FROM AUTHOR]

Purpose: San Luis Potosí is one of the largest metal producers; mining activity has been responsible for metal emissions for over 100 years, from several sources (deposits, tailings, effluents, and dusts) generating effects in human and ecosystem health. The objective of this study was to evaluate the effect of the concentrations of heavy metals in the soil health of four municipalities of San Luis Potosí contaminated with mine tailings, using enzyme activity as a biochemical endpoint. Materials and methods: Four municipalities contaminated with residues of historical mining activity were analyzed (25 topsoil samples per type of site contaminated and reference). The parameters that were analyzed included pH; organic matter (OM); electrical conductivity (EC); percentage of clay, As, Cd, Cr, Cu, Hg, Pb, and Zn; and arylsulfatase (ARS), β-glucosidase (BG), urease (UR), and fluorescein diacetate hydrolysis (FDA) activities in soil. Differences among the parameters per municipality and type of site were evaluated using a factorial analysis of variance. The relationships were analyzed by Pearson's correlation and a stepwise distance-based linear model permutation test (DistLM). Results were visualized using a distance-based redundancy analysis (dbRDA). A hazard quotient (HQ) for metals was calculated in order to estimate the effects on soil microbial processes. Results and discussion: A concentration gradient (mg/kg) of Zn (4744.5-65,585.7), Pb (1321.0-31,932.2), As (ND-8736.7), and Cu (130.9-8475.4) was found in the contaminated sites. The HQ showed a very high hazard level for the elements detected in all contaminated sites (1.4-655.8). The pattern of enzymatic inhibition found was ARS (95.8 %), UR (90.6 %), FDA (86.9 %), and BG (76.0 %). Strong negative relationships were observed among enzymatic activities and heavy metals in the following inhibitory effect Cu > As > Zn > Pb. Metals and covariables explained from 84 to 86 % of variability in enzyme activity. EC, Cu, and As showed a strong inhibitory effect; and parameters such as OM, pH, and clay were found to have a slightly inducing effect. Conclusions: In this study, the heavy metal concentrations were higher than the ones obtained in other reports for this region. The HQ reveals the presence of possible risks for the health of life in the region. The decrease of enzyme activities in soil could trigger adverse changes in the flow of matter and energy in ecosystems. This study provides a field baseline that could be part of a long-term monitoring program for these locations. [ABSTRACT FROM AUTHOR]