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Background & objective: The study aimed to assess the total prevalence of functional gastrointestinal disorders (FGIDs), and separately, irritable bowel syndrome (IBS) among adults and to determine their potential association with fructose consumption. Materials & Methods: Data from the Hellenic National Nutrition and Health Survey (HNNHS) were included (3798 adults; 58.9% females). Information regarding FGID symptomatology was assessed using self-reported physician diagnosis questionnaires the reliability of which were screened using the ROME III, in a sample of the population. Fructose intake was estimated from 24 hour recalls and the MedDiet score was used to assess adherence to the Mediterranean diet. Results: The prevalence of FGID symptomatology was 20.2%, while 8.2% had IBS (representing 40.2% of total FGID). The likelihood of FGID were 28% higher (95%CI: 1.03-1.6) and of IBS 49% (95%CI: 1.08-2.05) in individuals with higher fructose intake than with lower intake (3rd tertile compared to 1st). When area of residence was accounted for, individuals residing in the Greek islands, had a significantly lower probability of FGID and IBS compared to those residing in Mainland and the main Metropolitan areas, with Islanders also achieving a higher MedDiet score and lower added sugar intake, comparatively to inhabitants of the main metropolitan areas. Conclusions: FGID and IBS symptomatology was most prominent among individuals with higher fructose consumption, and this was most conspicuous in areas with a lower Mediterranean diet adherence, suggesting that the dietary source of fructose rather than total fructose should be examined in relation to FGID.

Through several pathological mechanisms, chronic stress contributes to the development of “osteosarcopenic obesity”, a clinical syndrome that includes impairments in the structure and function of a patient’s bones, skeletal muscles, and adipose tissue. This syndrome, which could be alternatively called “chronic stress and inflammation syndrome”, has its genesis in early life and, by the age of 50–60 years, affects up to two-thirds of Western populations. Chronic psycho-socioeconomic stress and lifestyle factors, such as a sedentary life, poor quality nutrition, irregular daily schedules, and inadequate sleep, which all act on a genetic and epigenetic predisposition background, play essential pathogenic roles in the development of this widespread syndrome. Key pathogenic mediators are those of the stress system and inflammatory reaction. Lifestyle changes, in combination with stress management, can prevent, arrest, or reverse this debilitating syndrome.

Adopting a healthy lifestyle during childhood could improve physical and mental health outcomes in adulthood and reduce relevant disease burdens. However, the lifestyles of children with mental, behavioral, and developmental disorders (MBDDs) remains under-described within the literature of public health field. This study aimed to examine adherence to 24-hour movement guidelines among children with MBDDs compared to population norms and whether these differences are affected by demographic characteristics.Data were from the 2016-2020 National Survey of Children's Health-a national, population-based, cross-sectional study. We used the data of 119,406 children aged 6 to 17 years, which included 38,571 participants with at least 1 MBDD and 80,835 without. Adherence to the 24-hour movement guidelines was measured using parent-reported physical activity, screen time, and sleep duration.Among children with MBDDs, 20.3%, 37.0%, 60.7%, and 77.3% met the physical activity, screen time, sleep, and at least 1 of the 24-hour movement guidelines. These rates were lower than those in children without MBDDs (22.8%, 46.2%, 66.7%, and 83.4%, respectively; all p values0.001). Children with MBDDs were less likely to meet these guidelines (odds ratio (OR) = 1.21, 95% confidence interval (95%CI): 1.13-1.30; OR = 1.37, 95%CI: 1.29-1.45; OR = 1.29, 95%CI: 1.21-1.37; OR = 1.45, 95%CI: 1.35-1.56) than children without MBDDs. Children with emotional disorders had the highest odds of not meeting these guidelines (OR = 1.43, 95%CI: 1.29-1.57; OR = 1.48, 95%CI: 1.37-1.60; OR = 1.49, 95%CI: 1.39-1.61; OR = 1.72, 95%CI: 1.57-1.88) in comparison to children with other MBDDs. Among children aged 12-17 years, the difference in proportion of meeting physical activity and screen time guidelines for children with versus children without MBDD was larger than that among children aged 6-11 years. Furthermore, the above difference of meeting physical activity guidelines in ethnic minority children was smaller than that in white children.Children with MBDDs were less likely to meet individual or combined 24-hour movement guidelines than children without MBDDs. In educational and clinical settings, the primary focus should be on increasing physical activity and limiting screen time in children aged 12-17 years who have MBDDs; and specifically for white children who have MBDDs, increasing physical activity may help.

Dickeya solani, a plant-pathogenic bacterium, produces solanimycin, a potent hybrid polyketide/nonribosomal peptide (PKS/NRPS) anti-fungal compound. The biosynthetic gene cluster responsible for synthesis of this compound has been identified. Because of instability, the complete structure of the compound has not yet been elucidated, but LC-MS2 identified that the cluster produces two main compounds, solanimycin A and B, differing by a single hydroxyl group. The fragmentation pattern revealed that the central part of solanimycin A is a hexapeptide, Gly-Dha-Dha-Dha-Dha-Dha (where Dha is dehydroalanine). This is supported by isotopic labeling studies using labeled serine and glycine. The N-terminal group is a polyketide-derived C16 acyl group containing a conjugated hexaene, a hydroxyl, and an amino group. The additional hydroxyl group in solanimycin B is on the α-carbon of the glycine residue. The incorporation of five sequential Dha residues is unprecedented because there is only one NRPS module in the cluster that is predicted to activate and attach serine (which is subsequently dehydrated to Dha), meaning that this NRPS module must act iteratively. While a few other iterative NRPS modules are known, they all involve iteration of two or three modules. We believe that the repetitive use of a single module makes the solanimycin biosynthetic pathway unique among NRPSs so far reported.

On 8–9 November 2022, the European Society of Pharmacogenomics and Personalised Therapy organized its sixth biennial congress, in Belgrade, Serbia (congress website: www.sspt.rs ). The congress aimed to address the current status and future perspectives of pharmacogenomics, share latest knowledge in the field of precision medicine and showcase the implementation of clinical applications in pharmacogenomics/pharmacogenetics. The 2 day congress consisted of 17 lectures given by key-opinion leaders and included a poster session plus discussions. The meeting was a great success by generating an informal environment and enabling the exchange of information between 162 participants from 16 different countries.

BACKGROUND: Transcriptomic studies of the brains of schizophrenia (SZ) patients have produced abundant but largely inconsistent findings about the disorders pathophysiology. These inconsistencies might stem not only from the heterogeneous nature of the disorder, but also from the unbalanced focus on particular cortical regions and protein-coding genes. Compared to protein-coding transcripts, long intergenic non-coding RNA (lincRNA) display substantially greater brain region and disease response specificity, positioning them as prospective indicators of SZ-associated alterations. Further, a growing understanding of the systemic character of the disorder calls for a more systematic screening involving multiple diverse brain regions. AIM: We aimed to identify and interpret alterations of the lincRNA expression profiles in SZ by examining the transcriptomes of 35 brain regions. METHODS: We measured the transcriptome of 35 brain regions dissected from eight adult brain specimens, four SZ patients, and four healthy controls, using high-throughput RNA sequencing. Analysis of these data yielded 861 annotated human lincRNAs passing the detection threshold. RESULTS: Of the 861 detected lincRNA, 135 showed significant region-dependent expression alterations in SZ (two-way ANOVA, BH-adjusted p 0.05) and 37 additionally showed significant differential expression between HC and SZ individuals in at least one region (post hoc Tukey test, p 0.05). For these 37 differentially expressed lincRNAs (DELs), 88% of the differences occurred in a cluster of brain regions containing axon-rich brain regions and cerebellum. Functional annotation of the DEL targets further revealed stark enrichment in neurons and synaptic transmission terms and pathways. CONCLUSION: Our study highlights the utility of a systematic brain transcriptome analysis relying on the expression profiles measured across multiple brain regions and singles out white matter regions as a prospective target for further SZ research.

The poultry sector is considered to be one of the most industrialized sectors of livestock production. Although the livestock sector contributes the 14.5% of total anthropogenic greenhouse gas (GHG) emissions, less attention has been paid in the respective emissions of the poultry sector compared to other farmed animals such as ruminants. The aim of the study was to estimate the carbon footprint of the poultry sector (layers, broilers, and backyards) in the Greek territory during the last 60 years as a means of exploring further mitigation strategies. Tier 2 methodology was used to estimate GHG emissions. Different mitigation scenarios related to changes in herd population, feeds, and manure management were examined. GHG emissions showed an increased trend over time. The different scenarios explored showed moderate to high mitigating potential depending on the parameters that were changed. Changes in manure management or diet revealed to have a higher potential to eliminate GHG emissions. Changes in population numbers showed a low mitigating potential. However, if mortality could be improved within industrialized farming systems, then it could be an indirect increase in product quantities with a slight increase in emissions. Therefore, depending on national priorities, the sector could improve its environmental impact by targeting aspects related to husbandry/management practices.

Background Data are sparse regarding the safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (MS). Objective To estimate (1) the pooled proportion of MS patients experiencing relapse among vaccine recipients; (2) the rate of transient neurological worsening, adverse events, and serious adverse events; (3) the previous outcomes of interest for different SARS-CoV-2 vaccine types. Methods Systematic review and meta-analysis of pharmacovigilance registries and observational studies. Results Nineteen observational studies comprising 14,755 MS patients who received 23,088 doses of COVID-19 vaccines were included. Mean age was 43.3 years (95% confidence interval (CI): 40–46.6); relapsing-remitting, secondary-progressive, primary-progressive MS and clinically isolated syndrome were diagnosed in 82.6% (95% CI: 73.9–89.8), 12.6% (95% CI: 6.3–20.8), 6.7% (95% CI: 4.2–9.9), and 2.9% (95% CI: 1–5.9) of cases, respectively. The pooled proportion of MS patients experiencing relapse at a mean time interval of 20 days (95% CI: 12–28.2) from vaccination was 1.9% (95% CI: 1.3%–2.6%; I2 = 78%), with the relapse risk being independent of the type of administered SARS-CoV-2-vaccine ( p for subgroup differences = 0.7 for messenger RNA (mRNA), inactivated virus, and adenovector-based vaccines). After vaccination, transient neurological worsening was observed in 4.8% (95% CI: 2.3%–8.1%) of patients. Adverse events and serious adverse events were reported in 52.8% (95% CI: 46.7%–58.8%) and 0.1% (95% CI: 0%–0.2%) of vaccinations, respectively. Conclusion COVID-19 vaccination does not appear to increase the risk of relapse and serious adverse events in MS. Weighted against the risks of SARS-CoV-2-related complications and MS exacerbations, these safety data provide compelling pro-vaccination arguments for MS patients.

Recognizing the identity of conspecifics is important for survival and social interactions. In sheep, vocal individuality enhances postnatal recognition and strengthens the mother-offspring bond. Although previous studies report vocal individuality in an early postnatal period (3–15 days of life), scarce information exists on whether individuality occurs at a later postnatal time point. The aim of the study was to identify whether individuality in acoustic cues is expressed in ewes' and their lambs' bleats at 40 days post-partum. Dairy ewes ( N = 21) and their suckling offspring ( n = 30) were isolated separately without hearing or seeing each other, and vocalizations were recorded. Different approaches for estimating individuality on 18 determined acoustic parameters were implemented. All parameters showed individuality, but higher individuality appeared in those related with source and spectral characteristics. A discriminant function analysis showed similar levels of individuality between ewes and lambs, but lower than that reported in an earlier postnatal time, suggesting that ewes and lambs do not need strong individualized cues at the examined time point. In both cases, jitter was the only common parameter, suggesting its importance. Distinctive cues were noted between siblings. Ewes displayed vocal individuality at their dry season (a later time point than suckling period), which was based on amplitude-related acoustic parameters.

A correlation between band alignment at an electron transport layer/perovskite interface and the locus of hysteresis in perovskite solar cells is proposed.

The exquisite sensitivity of the NMR chemical shift to local environment makes it an ideal probe to assess atomic level perturbations in proteins of all sizes and structural compositions. Recent advances in solution and solid-state NMR spectroscopy of biomolecules have leveraged the chemical shift to report on short- and long-range couplings between individual amino acids to establish "networks" of residues that form the basis of allosteric pathways that transmit chemical signals through the protein matrix to induce functional responses. The simple premise that thermodynamically and functionally coupled regions of a protein (i.e. active and allosteric sites) should be reciprocally sensitive to structural or dynamic perturbations has enabled NMR spectroscopy, the premier method for molecular resolution of protein structural fluctuations, to occupy a place at the forefront of investigations into protein allostery. Here, we detail several key methods of NMR chemical shift analysis to extract mechanistic information about long-range chemical signaling in a protein, focusing on practical methodological aspects and the circumstances under which a given approach would be relevant. We also detail some of the experimental considerations that should be made when applying these methods to specific protein systems.

To determine if the tidal volume (VProspective proof-of-concept study.A total of 23 adult client-owned dogs undergoing elective orthopedic surgery.Dogs were anesthetized and ventilated with a volume-controlled mechanical ventilator with constant respiratory rate (fVDogs on volume-controlled ventilators may be ventilated at a higher V

Background: There are limited data regarding the prevalence of distinct clinical, neuroimaging and genetic markers among patients diagnosed with cerebral amyloid angiopathy–related inflammation (CAA-ri). We sought to determine the prevalence of clinical, radiological, genetic and cerebrospinal fluid biomarker findings in patients with CAA-ri. Methods: A systematic review and meta-analysis of published studies including patients with CAA-ri was conducted to determine the prevalence of clinical, neuroimaging, genetic and cerebrospinal fluid biomarker findings. Subgroup analyses were performed based on (1) prospective or retrospective study design and (2) CAA-ri diagnosis with or without available biopsy. We pooled the prevalence rates using random-effects models and assessed the heterogeneity using Cochran-Q and I 2 -statistics. Results: We identified 4 prospective and 17 retrospective cohort studies comprising 378 patients with CAA-ri (mean age, 71.5 years; women, 52%). The pooled prevalence rates were as follows: cognitive decline at presentation 70% ([95% CI, 54%–84%]; I 2 =82%), focal neurological deficits 55% ([95% CI, 40%–70%]; I 2 =82%), encephalopathy 54% ([95% CI, 39%–68%]; I 2 =43%), seizures 37% ([95% CI, 27%–49%]; I 2 =65%), headache 31% ([95% CI, 22%–42%]; I 2 =58%), T2/fluid-attenuated inversion recovery-hyperintense white matter lesions 98% ([95% CI, 93%–100%]; I 2 =44%), lobar cerebral microbleeds 96% ([95% CI, 92%–99%]; I 2 =25%), gadolinium enhancing lesions 54% ([95% CI, 42%–66%]; I 2 =62%), cortical superficial siderosis 51% ([95% CI, 34%–68%]; I 2 =77%) and lobar macrohemorrhage 40% ([95% CI, 11%–73%]; I 2 =88%). The prevalence rate of the ApoE (Apolipoprotein E) ε4/ε4 genotype was 34% ([95% CI, 17%–53%]; I 2 =76%). Subgroup analyses demonstrated no differences in these prevalence rates based on study design and diagnostic strategy. Conclusions: Cognitive decline was the most common clinical feature. Hyperintense T2/fluid-attenuated inversion recovery white matter lesions and lobar cerebral microbleeds were by far the most prevalent neuroimaging findings. Thirty-four percent of patients with CAA-ri have homozygous ApoE ε4/ε4 genotype and scarce data exist regarding the cerebrospinal fluid biomarkers and its significance in these patients.

Multiple pathologies may underlie corticobasal syndrome (CBS), including Alzheimer's disease (AD). Typical amnestic AD is characterized by early selective hippocampal atrophy. The profile of hippocampal atrophy in AD patients presenting as CBS (CBS-AD), compared to CBS patients of non-AD pathologies (CBS-nAD) and amnestic AD patients, has not been studied.To compare hippocampal subfield atrophy patterns between CBS-AD, CBS-nAD, typical amnestic AD patients, and control subjects.Automated hippocampal subfield volumetry was performed via the hippocampal subfield segmentation pipeline of Freesurfer 6.0 on 3D T1-weighted images. CBS patients were classified as CBS-AD or CBS-nAD based on CSF AD biomarkers by applying the AT(N) classification system. Mean volumes of nine hippocampal subfields, head-body-tail segments, total hippocampus, and entorhinal and parahippocampal gyrus cortical thickness were measured.Eighty-three subjects were included (CBS-AD: n = 14; CBS-nAD: n = 17; amnestic AD: n = 29; controls: n = 23). CBS-AD patients had greater whole hippocampal and hippocampal subfield atrophy compared to CBS-nAD. CBS-AD and amnestic AD patients did not differ in subfield volumes. CBS-nAD did not exhibit hippocampal atrophy compared to controls, with the exception of fimbria. (Cohen's d = 1.27; p = 0.038). Presubiculum (Cohen's d = 1.00; p = 0.002) and hippocampal body (Cohen's d = 0.95; p = 0.001) volumes exhibited the greatest differences between CBS-AD and CBS-nAD. Hippocampal subfield volume provided combined sensitivity and specificity 80% for the discrimination of CBS-AD from CBS-nAD.CBS-AD and amnestic AD patients exhibit comparable, and significantly greater hippocampal atrophy compared to CBS-nAD patients. Hippocampal subfield volumetry in CBS is indicative of an AD underlying pathology.

Purpose The purpose of this paper is to analyze media coverage of the pharmaceutical industry before and after the COVID-19 lockdown to determine whether the coverage changed in light of a global health-care crisis and the fast-track development of vaccines and antiviral treatments. Design/methodology/approach The top five US newspapers were audited, comparing the 12-month periods before and after March 2020 coinciding with the pandemic lockdown, yielding 493 front-page articles and editorials. Each headline and full-text article was separately analyzed and categorized as either positive, negative or neutral toward the pharmaceutical industry. A frequency analysis of the hot button issues covered in each article was conducted. Findings Year 1 and Year 2 audit results were compared to identify changes in media coverage pre- and post-lockdown. The amount of coverage of the industry increased 145% and the tone of both headlines and articles shifted dramatically. Only one of the five newspapers had a net positive article rating of the industry pre-lockdown, four of five were net positive post-lockdown. The proportion of positive headlines increased 165%. The top issues discussed in the coverage shifted from persistent challenges for the industry (e.g. opioid crisis, high cost of drugs) to the emergence of the virus and status of vaccine development. Originality/value This research establishes how media coverage of the pharmaceutical industry changed as the industry responded to a global health-care crisis and identifies implications for industry stakeholders.

The little owl (Athene noctua) is a common raptor in Mediterranean habitats. To acquire more information on its diet, this study identified cranial and post-cranial skeletal material from 70 owl pellets collected during the 2016 and 2017 breeding seasons. The material was used to quantify the little owl’s relative prey abundance using MNI (minimum number of individuals), a taphonomical unit. This study is the first to examine the diet of the little owl in the Peloponnese (southern Greece). After examining 3,691 isolated skeletal and exoskeletal remains from the processed pellets, a total of 78 and 108 prey items were recorded for the two consecutive years. This study, in congruence with previous research, showed that in both years the little owl favoured primarily small mammals and arthropods, with a clear predominance of Thomas’s pine vole (Microtus thomasi) and arthropods from the class Diplopoda. Finally, a redundancy discriminant analysis (RDA) was applied to our two-year results, along with those from similar studies in the Mediterranean region, to examine the relationship between habitat types and prey taxa, which supported the little owl’s opportunistic feeding behaviour, depending on variation of ecological factors.

Paint smears represent a type of automotive paint sample found at a crime scene that is problematic for forensic automotive paint examiners to analyze as there are no reference materials present in automotive paint databases to generate hit-lists of potential suspect vehicles. Realistic paint smears are difficult to create in a laboratory and have also proven challenging to analyze because of the mixing of the various automotive paint layers. A procedure based on an impact tester has been developed to create smears to simulate paint transfer between vehicles during a collision. Data collected from 24 original equipment manufacturer (OEM) paints in simulated collisions using an impact tester with a steel (inert) substrate to simulate vehicle to vehicle collisions shows that attenuated total reflection infrared microscopy can isolate individual paint layers. For each OEM paint sample, the corresponding smear obtained was dependent upon the conditions used. By varying these conditions, the number of distinct layers obtained could be tuned for each of the OEM paints investigated. Furthermore, the IR spectrum of each layer extracted from the paint smear using alternating least squares was found to compare favorably to an in-house OEM paint infrared spectral library for each layer as the correct match (make and model of the vehicle from which the smear originated) was always found as a top five hit in the hit-list. The results of this study indicate that paint smears developed using an impactor can serve as the basis of realistic proficiency tests for forensic laboratories.

Sex has been universally acknowledged as a confounding factor in every type of biological study, while there are strong sex differences in morbidity along the lifespan. Humans have almost identical genomes (99.2%), yet minor variance in their DNA produces remarkable phenotypic diversity across the human population. On the other hand, metagenomic analysis of the human microbiome is more variable, depending on the sex, lifestyle, geography, and age of individuals under study. Immune responses in humans also exhibit variations, with an especially striking sexual dimorphism, which is at play in several other physiologic processes. Sex steroids have noticeable effects on the composition of the human microbiome along the lifespan, accompanied by parallel changes in immunity and the stress response. Gut microsex/genderome, a recently coined term, defines the sexually dimorphic gut microbiome. Apart from the sex steroids, the stress hormones are also at play in the proliferation of microbes. This review summarizes the concept of gut microsex/genderome under the prism of recent studies on the interrelations of the sexually dimorphic microbiome with immunity and stress.

At the core of the CRISPR-Cas9 genome-editing technology, the endonuclease Cas9 introduces site-specific breaks in DNA. However, precise mechanistic information to ameliorating Cas9 function is still missing. Here, multi-microsecond molecular dynamics, free-energy and multiscale simulations are combined with solution NMR and DNA cleavage experiments to resolve the catalytic mechanism of target DNA cleavage. We show that the conformation of an active HNH nuclease is tightly dependent on the catalytic Mg(2+), unveiling its cardinal structural role. This activated Mg(2+)-bound HNH is consistently described through molecular simulations, solution NMR and DNA cleavage assays, revealing also that the protonation state of the catalytic H840 is strongly affected by active site mutations. Finally, ab-initio QM(DFT)/MM simulations and metadynamics establish the catalytic mechanism, showing that the catalysis is activated by H840 and completed by K866, rationalising DNA cleavage experiments. This information is critical to enhance the enzymatic function of CRISPR-Cas9 toward improved genome-editing.

Butylated hydroxytoluene (BHT) is a synthetic antioxidant widely used in many industrial sectors. BHT is a well-studied compound for which there are many favorable regulatory decisions. However, a recent opinion by the French Agency for Food, Environmental and Occupational Health and Safety (ANSES) hypothesizes a role for BHT in endocrine disruption (ANSES (2021). This opinion is based on observations in mostly rat studies where changes to thyroid physiology are observed. Enzymatic induction of Cytochrome P450-mediated thyroid hormone catabolism has been proposed as a mechanism for these observations, however, a causal relationship has not been proven. Other evidence proposed in the document includes a read across argument to butylated hydroxyanisole (BHA), another Community Rolling Action Plan (CoRAP)-listed substance with endocrine disruption concerns. We tested the hypothesis that BHT is an endocrine disruptor by using a Next Generation Risk Assessment (NGRA) method. Four different cell lines: A549, HCC1428, HepG2, and MCF7 were treated with BHT and a series of BHT analogs at 5 different concentrations, RNA was isolated from cell extracts and run on the L1000 gene array platform. A toxicogenomics-based assessment was performed by comparing BHT’s unique genomic signature to a large external database containing signatures of other compounds (including many known endocrine disruptors) to identify if any endocrine disruption-related modes of action (MoAs) are prevalent among BHT and other compounds with similar genomic signatures. In addition, we performed a toxicogenomics-based structure activity relationship (SAR) assessment of BHT and a series of structurally similar analogs to understand if endocrine disruption is a relevant MoA for chemicals that are considered suitable analogs to BHT using the P&G read across framework (Wu et al., 2010). Neither BHT nor any of its analogs connected to compounds that had endocrine activity for estrogens, androgens, thyroid, or steroidogenesis.

Exogenous silicone has been reported to migrate to anatomic sights far from an initial injection or implantation site; this phenomenon has been rarely described in the ocular adnexa, especially in the eyelids. We document 3 additional cases of distant migration of silicone implanted elsewhere in the body to the eyelids and review the prior literature on this uncommon event.A retrospective chart review of 3 patients was conducted along with analysis of diagnostic histopathology. A comprehensive review of the literature regarding dissemination or migration of silicone to the eyelids in patients with either silicone breast implants or silicone facial filler use was performed.Cases of silicone migrating to the eyelids from silicone breast implants and silicone-based facial filler are outlined in Tables 1 and 2, respectively. There are 4 total reports of women with silicone breast implants, including the 2 described here, with evidence of migration of silicone to the eyelid. Similarly, 5 cases of silicone-based facial filler with resultant migration of filler to the eyelids were identified, including 2 of the cases presented in this report (1 patient had both silicone breast implants and silicone facial filler).Silicone is chemically inert, but is known to travel throughout the body, causing a resultant foreign body response in tissue that can adversely affect even the eyelids. Silicone has a relatively characteristic histologic appearance and diagnosis of silicone granuloma highlights the importance of obtaining a thorough clinical history, particularly regarding prior cosmetic injections or breast enhancement surgery. Foreign material/foreign body granuloma is important to consider in patients with deep eyelid nodules of unclear etiology.

This study presents a simple framework methodology for selecting the most appropriate locations for managed aquifer recharge (MAR). The proposed approach is applicable to aquifers that are located in coastal or mountainous areas and are used either for agricultural or industrial (e.g., mining) activities. A characteristic case study for the identification of the areas that are the most suitable for aquifer recharge using a GIS multi-criteria decision analysis (GIS-MCDA) method by means of MAR type spreading methods is the Geropotamos basin, Crete, Greece. Criteria combining a high relevance and high data availability, and providing unique information, were selected to assess the suitability of aquifer recharge in the basin. The criteria applied to evaluate the sites’ suitability for MAR spreading methods are hydrogeology, slope, land use, rainfall, groundwater level, soil texture and distance to source water. This study uses the ‘Pairwise comparison’ to assign criteria weights, as part of the Analytic Hierarchy Process (AHP), and examines four different scenarios. In all four scenarios, downstream areas, and close to the river Geropotamos, coincide as the most appropriate for aquifer recharge.

Students often struggle with visualizing protein structures when working with two-dimensional textbook and lecture materials, so introducing them to 3D visualization software developed by and for structural biologists offers them a unique opportunity to work with authentic data while furthering their spatial reasoning skills and understanding of molecular structure and function. This article presents an active learning virtual laboratory in which students use authentic structural biology data to investigate the effects of both hypothetical and real-world SARS-CoV-2 mutations on the virus’s ability to bind to human ACE2 receptors and infect a host, causing COVID-19. Through this activity, introductory-level college students or advanced high school students gain a better understanding of applied biology, such as how vaccines and treatments are designed, as well as strengthening their understanding of core disciplinary concepts, such as the relationship between protein structure and function and the central dogma of molecular biology. While there were challenges during the pilot phase of activity development due to COVID-19 restrictions, students in the pilot groups came away from the activity with deeper understanding of the relationship between proteins and amino acid sequences and a new appreciation for the ways researchers design treatments for and study viruses.

This paper presents an air pluviation system, developed to facilitate 1g physical model tests in granular soils. The deposition process is fully automated and requires minimal input from the operator, thereby significantly reducing the time required to deposit large volumes of granular material, improving the uniformity of the prepared specimens and the reliability of test results. The components comprising the pluviation system have been calibrated to produce loose-to-very dense sand beds, of relative density that ranges between Dr = 7% and > 100% of the maximum density achieved with the procedures described in the pertinent standards. The testing chamber where sand is deposited is instrumented with an array of pressure sensors, and the rig is equipped with a miniature cone penetration testing (mini-CPT) device. Measurements from the earth pressure sensors and cone tip resistance profiles are used to evaluate how friction at the sand–chamber interfaces affects the distribution of geostatic stresses inside the chamber, the uniformity of sand beds and boundary effects during deposition and during mini-CPT testing. The air pluviation system allows preparing layered sand profiles by adjusting the deposition parameters on the fly, and this feature is demonstrated through the analysis of mini-CPT tests performed in layered sand beds.

In 2022, the FIFA World Cup has been scheduled to take place in Qatar in November and December, months which coincide with the in-season period of the European soccer season. This will be challenging for the staff of the participating national teams and the domestic clubs to which participating players are attached. The aim of this letter to the editor is to propose solutions on how to manage the associated challenges. Regular training and competition over the course of a season in European professional soccer is generally characterized by a pre-competition preparation period of five to six weeks, followed by two competition phases, interspersed with a winter break (Eliakim et al., 2018). Certain leagues such as the English Premier League do not typically have a winter break meaning that games are played almost continuously across the season. During World Cup years, there is usually an average of four to five weeks between the end of national domestic championships and the start of the World Cup tournament (Table 1, Figure 1) which traditionally takes place during the off-season period. However, in 2022, the FIFA World Cup has been scheduled to take place in November and December, months which coincide with the in-season period of the European soccer season (Figure 1). With the World Cup being staged during this part of the season, many national team players (notably those in the major European Leagues) will have just one week of preparation between the last match of their domestic leagues and the start of the World Cup tournament (November 20th, 2022). More precisely, the major European soccer leagues will interrupt match schedules between November 9th and 13th with differences in the number of games completed at this time of the season ranging from 14 to 17 across the various leagues (Table 2). The physical and mental demands placed on modern professional players have steadily risen over recent years due to an increase in the number of matches played during congested periods across the season (Anderson et al., 2016). Since the number of matches is not evenly distributed across the typical 40-week season, players can often compete in as many as three matches in a seven-day period. Aside from the physical and mental demands that are imposed during a match, players might experience insufficient recovery between these games; in part due to extensive travelling which can disrupt the sleep/wake cycle (Lastella et al., 2019). Indeed, poor quality of sleep and the stress induced by a match can negatively affect physical fitness and may even increase the risk of sustaining injuries and/or infections (Clemente et al., 2021) in the period leading up to the World Cup. National teams are composed of players from different leagues who have varying levels of exposure to match-play (e.g., starters, non-starters) in terms of the average weekly volume of soccer matches at their clubs (“Rapports - Observatoire du football CIES”). Moreover, both starters and non-starters are exposed to different external match and training loads (Anderson et al., 2016). External loads have previously been defined as the overall volume of activity that a player performs during both training sessions and matches (Ravé et al., 2020). There is evidence that this metric correlates with a player’s physical fitness status (Clemente et al., 2019) and their injury risk (Malone et al., 2017). Accordingly, it will be challenging for national teams to manage the fitness of players such that they are physically ready to play at the World Cup tournament. This is especially applicable to individuals who play in the major European leagues and we note a significant contrast between European match schedules and those on other continents. For example, in Major League Soccer (MLS) in North America, match schedules will be interrupted from November 5th, 15 days before the World Cup tournament begins. Similarly, in the Japanese J-League in Asia, Saudi Pro League and Qatar Star League, matches will be interrupted one month before the World Cup tournament begins, leaving more time for players on these continents to prepare. It is also important to note that the French, Spanish and English domestic championships will resume their match schedules on December 27th which is just ten days after the end of the World Cup (Figure 1). Clubs will clearly want their players to return uninjured and with sufficient fitness levels to resume domestic competition but these goals could be compromised by the aforementioned scheduling of the World Cup tournament.

Although ACTH is considered a secondary regulator of aldosterone production, patients with apparent essential hypertension have been treated with mineralocorticoid receptor antagonists (MRAs). In this study, we aimed to identify potentially damaging variants that might be implicated in the phenotype of a well-characterized cohort of 21 hypertensive patients without PA but with stress-induced aldosterone hypersecretion. The patients' blood pressure was normalized though MRA administration.Genetic screening was performed through whole-exome sequencing (WES), and variants in PA-associated or in ion-channels of aldosterone-regulating genes were prioritized. Variants with population frequency 0.01, predicted to alter protein structure and classified as likely pathogenic by in silico tools, were retained.Qualifying variants were identified in nine of the 21 patients screened. Seven patients were carriers of six potentially damaging variants in six genes associated with PA (KCNK9, KCNK5, ATP13A3, SLC26A2, CACNA1H, and CACNA1D). A novel variant in the KCNK9 gene (p.V221M) is reported. Our analysis revealed two variants in two novel susceptibility genes for aldosterone hypersecretion, namely, KCNK16 (p.P255H) and CACNA2D3 (p.V557I).WES revealed potentially damaging germline variants in genes participating in aldosterone synthesis/regulating pathways in 9/21 patients of our cohort. The variants identified might play a role in aldosterone hypersecretion under conditions of stress. The potential pathogenicity of these variants should be examined in future functional studies.

Remdesivir is an adenosine analogue that has a cyano substitution in the C1' position of the ribosyl moiety and a modified base structure to stabilize the linkage of the base to the C1' atom with its strong electron-withdrawing cyano group. Within the replication-transcription complex (RTC) of SARS-CoV-2, the RNA-dependent RNA polymerase nsp12 selects remdesivir monophosphate (RMP) over adenosine monophosphate (AMP) for nucleotide incorporation but noticeably slows primer extension after the added RMP of the RNA duplex product is translocated by three base pairs. Cryo-EM structures have been determined for the RTC with RMP at the nucleotide-insertion (

Ectoine is a widespread osmolyte enabling halophilic bacteria to withstand high osmotic stress that has many potential applications ranging from cosmetics to its use as a therapeutic agent.The aim of this study was to compare the efficacy and tolerability of ectoine 1% and hyaluronic acid 0.1% containing (EHA) cream with a vehicle cream in children with mild-to-moderate atopic dermatitis (AD).A randomized, controlled, observer-blind, multicenter clinical trial was conducted in children aged 2-18 years, diagnosed with mild-to-moderate AD (SCORAD ≤20). Patients were randomized to either receiving EHA cream or vehicle cream twice daily for 4 weeks. The primary outcome measure was the mean change in objective SCORAD from baseline to the final visit. The secondary outcome measures included the mean change in Investigator's Global Assessment score, patient's judgment of efficacy and patient's assessment of pruritus. Safety of EHA cream was also assessed.A total of 70 patients (35 in each group) were randomized and 57 were included in the final analysis set. Based on SCORAD measurements, patients using EHA cream achieved superior clinical improvement compared to the control group at 28 days (p .001). EHA cream was also superior to the vehicle cream regarding all secondary outcome measures. Eight (23.5%) patients receiving EHA cream and two (5.7%) patients receiving vehicle cream experienced mild cutaneous adverse events (AEs).In children 2-18 years old with mild-to-moderate AD, EHA cream was superior to vehicle cream, with minor AEs.