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ABSTRACT Infections with multidrug-resistant bacteria pose a major healthcare problem which urges the need for novel treatment options. Besides its potent antiplatelet properties, ticagrelor has antibacterial activity against Gram-positive bacteria, including methicillin- and vancomycin-resistant Staphylococcus aureus (MRSA and VRSA). Several retrospective studies in cardiovascular patients support an antibacterial effect of this drug which is not related to its antiplatelet activity. We investigated the mechanism of action of ticagrelor in Staphylococcus aureus and model Bacillus subtilis, and assessed cross-resistance with two conventional anti-MRSA antibiotics, vancomycin and daptomycin. Bacillus subtilis bioreporter strains revealed ticagrelor-induced cell envelope-related stress responses. Sub-inhibitory drug concentrations caused membrane depolarization, impaired positioning of both the peripheral membrane protein MinD and the peptidoglycan precursor lipid II, and it affected cell shape. At the MIC, ticagrelor destroyed membrane integrity, indicated by the influx of membrane impermeable dyes, and lipid aggregate formation. Whole-genome sequencing of in vitro-generated ticagrelor-resistant MRSA clones revealed mutations in genes encoding ClpP, ClpX, and YjbH. Lipidomic analysis of resistant clones displayed changes in levels of the most abundant lipids of the Staphylococcus aureus membrane, for example, cardiolipins, phosphatidylglycerols, and diacylglycerols. Exogeneous cardiolipin, phosphatidylglycerol, or diacylglycerol antagonized the antibacterial properties of ticagrelor. Ticagrelor enhanced MRSA growth inhibition and killing by vancomycin and daptomycin in both exponential and stationary phases. Finally, no cross-resistance was observed between ticagrelor and daptomycin, or vancomycin. Our study demonstrates that ticagrelor targets multiple lipids in the cytoplasmic membrane of Gram-positive bacteria, thereby retaining activity against multidrug-resistant staphylococci including daptomycin- and vancomycin-resistant strains.IMPORTANCEInfections with multidrug-resistant bacteria pose a major healthcare problem with an urgent need for novel treatment options. The antiplatelet drug ticagrelor possesses antibacterial activity against Gram-positive bacteria including methicillin-resistant and vancomycin-resistant Staphylococcus aureus strains. We report a unique, dose-dependent, antibacterial mechanism of action of ticagrelor, which alters the properties and integrity of the bacterial cytoplasmic membrane. Ticagrelor retains activity against multidrug-resistant staphylococci, including isolates carrying the most common in vivo selected daptomycin resistance mutations and vancomycin-intermediate Staphylococcus aureus. Our data support the use of ticagrelor as adjunct therapy against multidrug-resistant strains. Because of the presence of multiple non-protein targets of this drug within the bacterial membrane, resistance development is expected to be slow. All these findings corroborate the accumulating observational clinical evidence for a beneficial anti-bacterial effect of ticagrelor in cardiovascular patients in need of such treatment.

BackgroundSurvivorship care plans (SCPs) are provided at the completion of cancer treatment to aid in the transition from active treatment to long-term survivorship. They describe the details of a patient’s diagnosis and treatment and offer recommendations for follow-up appointments, referrals, and healthy behaviors. The plans are currently paper-based and become outdated as soon as a patient’s health status changes. There is a need to digitize these plans to improve their accessibility, modifiability, and longevity. With current technology, SCPs can be linked to mobile devices and activity trackers so that patients can track health behaviors and compare them to their clinical goals, taking charge of their own health. ObjectiveA mobile app, POSTHOC (POST-Treatment Health Outcomes of Cancer Survivors), that digitizes the SCP was developed, with goals of integrating it with wearable technologies and electronic medical records. Herein, we are conducting a randomized controlled trial that evaluates the POSTHOC app versus the traditional SCP on total symptom burden in the early posttreatment period. MethodsWe will recruit 54 patients who have recently completed curative therapy for cancer (any type) in person and remotely. They will be randomized 2:1, POSTHOC:usual care (unblinded). Those randomized to the POSTHOC group will receive their SCP via the app and will choose to focus on nutrition or exercise for the duration of the study based on their individual plan and personal preferences. Those randomized to the control group will get a paper-based plan. At baseline, 6 weeks, and 12 weeks, we will evaluate patient-reported outcomes, including total symptom burden (web-based questionnaire), diet (24-hour Automated Self-Administered [ASA24]), and physical activity (Fitbit Charge 6 [Google LLC]). We will also collect quantitative and qualitative feedback on the usability of the app from those in the POSTHOC arm to improve the app for future implementation studies, with a specific focus on patient-provider communication. For feasibility, we will calculate the percentage of patients who used the POSTHOC app at least 3 times per week. We will use linear mixed models to evaluate the effects of the POSTHOC app versus those of usual care on other outcomes at weeks 6 and 12. ResultsThis trial is open to accrual in the University of Maryland Medical System as of March 2024, and as of July 3, 2024, a total of 20 participants have consented. ConclusionsThis study is among the first to digitize the SCP in a mobile app and test the effects of a mobile health–delivered behavioral health intervention on symptom burden in cancer survivors. Our results will provide evidence about the effects of health self-management on symptoms. This knowledge will be integral to larger randomized controlled studies, integration with the electronic medical record, and nationwide implementation. Trial RegistrationClinicalTrials.gov NCT05499663; https://clinicaltrials.gov/ct2/show/NCT05499663 International Registered Report Identifier (IRRID)DERR1-10.2196/59222

Abstract Background Pregnancy and childbirth have been connected to modified risk of a wide variety of conditions in later life, including neurodegenerative disorders and cancers. The presence, extent, and direction of the effect that childbearing status has on decreasing or increasing the risk of these conditions differs depending on the disease. The mechanisms by which pregnancy and childbirth modify the risk of diseases are still unknown. DNA methylation (DNAm) alterations that occur during pregnancy and persist after childbirth may help us understand this phenomenon. Results Blood DNAm was available from 89 women (28 parous; 61 nulliparous) at ages 18 and 26 years in the Isle of Wight birth cohort; no significant differences in the population characteristics were present between the analyzed population and the full cohort. We performed an epigenome-wide association study on 389,355 CpGs and identified 184 CpGs to be significantly differentially methylated between parous and nulliparous women after adjusting for confounders and multiple testing. Of these CpGs, 105 had regression coefficients in the same direction in an independent Mexico City based ELEMENT cohort, of which 13 were significant (replication P

Abstract Background The ascomycete fungus Anisogramma anomala causes Eastern Filbert Blight (EFB) on hazelnut (Corylus spp.) trees. It is a minor disease on its native host, the American hazelnut (C. americana), but is highly destructive on the commercially important European hazelnut (C. avellana). In North America, EFB has historically limited commercial production of hazelnut to west of the Rocky Mountains. A. anomala is an obligately biotrophic fungus that has not been grown in continuous culture, rendering its study challenging. There is a 15-month latency before symptoms appear on infected hazelnut trees, and only a sexual reproductive stage has been observed. Here we report the sequencing, annotation, and characterization of its genome. Results The genome of A. anomala was assembled into 108 scaffolds totaling 342,498,352 nt with a GC content of 34.46%. Scaffold N50 was 33.3 Mb and L50 was 5. Nineteen scaffolds with lengths over 1 Mb constituted 99% of the assembly. Telomere sequences were identified on both ends of two scaffolds and on one end of another 10 scaffolds. Flow cytometry estimated the genome size of A. anomala at 370 Mb. The genome exhibits two-speed evolution, with 93% of the assembly as AT-rich regions (32.9% GC) and the other 7% as GC-rich (57.1% GC). The AT-rich regions consist predominantly of repeats with low gene content, while 90% of predicted protein coding genes were identified in GC-rich regions. Copia-like retrotransposons accounted for more than half of the genome. Evidence of repeat-induced point mutation (RIP) was identified throughout the AT-rich regions, and two copies of the rid gene and one of dim-2, the key genes in the RIP mutation pathway, were identified in the genome. Consistent with its homothallic sexual reproduction cycle, both MAT1-1 and MAT1-2 idiomorphs were found. We identified a large suite of genes likely involved in pathogenicity, including 614 carbohydrate active enzymes, 762 secreted proteins and 165 effectors. Conclusions This study reveals the genomic structure, composition, and putative gene function of the important pathogen A. anomala. It provides insight into the molecular basis of the pathogen’s life cycle and a solid foundation for studying EFB.

Abstract Background During the wars in Afghanistan and Iraq most injuries to service members involved the musculoskeletal system. These wounds often occurred around joints, and in some cases result in traumatic arthrotomy—a diagnosis that is not always clear, especially when there is no concomitant articular fracture. The aim of the present study is to evaluate the diagnosis and treatment of peri-articular blast injuries without fracture. Methods The study cohort included 12 consecutive patients (12 involved extremities) who sustained peri-articular blast wounds of the extremities without fractures. The diagnosis of penetrating articular injury was based on clinical examination, radiographic findings, or aspiration. A peri-articular wound was defined as any wound, or radio-opaque blast fragment, within 5 cm of a joint. The New Injury Severity Score (NISS) was calculated for each patient. Four patients had upper, and 8 patients had lower extremity injuries. Nine of 12 patients had joint capsular penetration and underwent joint irrigation and debridement. Results Two patients had retained intra-articular metal fragments. One patient had soft tissue blast wounds within 5 cm of a joint but did not have joint capsule penetration. There were no significant differences (p = 0.23) between the distribution of wounds to upper versus lower extremities. However, there were a significantly greater number of blast injuries attributed to Improvised Explosive Devices (IEDs) than from other blast mechanisms (p = 0.01). Conclusion Extremity blast injuries in the vicinity of joints involving only soft tissues present a unique challenge in surgical management. A high index of suspicion should be maintained for joint capsular penetration so that intra-articular injuries may be appropriately treated.

Abstract Objective Chronic subdural hematoma (CSDH) is a common neurological condition and is typically treated with burr hole craniostomy. Nevertheless, conservative treatment may lead to spontaneous hematoma resolution in some patients. This study aims to describe the characteristics of patients who were treated conservatively without the eventual need for additional treatment. Methods Data were retrospectively collected from patients who were primarily treated conservatively in three hospitals in the Netherlands from 2008 to 2018. The Primary outcome was the nonnecessity of additional treatment within 3 months after the initial CSDH diagnosis. We used univariable and multivariable logistic regression analyses to identify factors associated with not receiving additional treatment. Results In this study, 83 patients were included and 61 patients (73%) did not receive additional treatment within 3 months. Upon first presentation, the patients had a Markwalder Grading Scale score (MGS) of 0 (n = 5, 6%), 1 (n = 43, 52%), and 2 (n = 35, 42%). Additional treatment was less often received by patients with smaller hematoma volumes (adjusted odds ratio [aOR] 0.78 per 10 mL; 95% confidence interval [CI] 0.64–0.92). Patients using antithrombotic medication also received less additional treatment, but this association was not significant (aOR 2.02; 95% CI 0.61–6.69). Conclusions Three quarters of the initially conservatively treated CSDH patients do not receive additional management. Typically, these patients have smaller hematoma volumes. Further, prospective research is needed to distinguish which patients require surgical intervention and in whom primary conservative treatment suffices.

Abstract Electronic health records (EHRs) contain a vast array of phenotypic data on large numbers of individuals, often collected over decades. Due to the wealth of information, EHR data have emerged as a powerful resource to make first discoveries and identify disparities in our healthcare system. While the number of EHR‐based studies has exploded in recent years, most of these studies are directed at associations with disease rather than pharmacotherapeutic outcomes, such as drug response or adverse drug reactions. This is largely due to challenges specific to deriving drug‐related phenotypes from the EHR. There is great potential for EHR‐based discovery in clinical pharmacology research, and there is a critical need to address specific challenges related to accurate and reproducible derivation of drug‐related phenotypes from the EHR. This review provides a detailed evaluation of challenges and considerations for deriving drug‐related data from EHRs. We provide an examination of EHR‐based computable phenotypes and discuss cutting‐edge approaches to map medication information for clinical pharmacology research, including medication‐based computable phenotypes and natural language processing. We also discuss additional considerations such as data structure, heterogeneity and missing data, rare phenotypes, and diversity within the EHR. By further understanding the complexities associated with conducting clinical pharmacology research using EHR‐based data, investigators will be better equipped to design thoughtful studies with more reproducible results. Progress in utilizing EHRs for clinical pharmacology research should lead to significant advances in our ability to understand differential drug response and predict adverse drug reactions.

Abstract Adverse effects of large artery stiffening are well established in the systemic circulation; stiffening of the proximal pulmonary artery (PPA) and its sequelae are poorly understood. We combined in vivo (n = 6) with ex vivo data from cadavers (n = 8) and organ donors (n = 13), ages 18 to 89, to assess whether aging of the PPA associates with changes in distensibility, biaxial wall strain, wall thickness, vessel diameter, and wall composition. Aging exhibited significant negative associations with distensibility and cyclic biaxial strain of the PPA (p ≤ 0.05), with decreasing circumferential and axial strains of 20% and 7%, respectively, for every 10 years after 50. Distensibility associated directly with diffusion capacity of the lung (R2 = 0.71, p = 0.03). Axial strain associated with right ventricular ejection fraction (R2 = 0.76, p = 0.02). Aging positively associated with length of the PPA (p = 0.004) and increased luminal caliber (p = 0.05) but showed no significant association with mean wall thickness (1.19 mm, p = 0.61) and no significant differences in the proportions of mural elastin and collagen (p = 0.19) between younger (50) ex vivo samples. We conclude that age‐related stiffening of the PPA differs from that of the aorta; microstructural remodeling, rather than changes in overall geometry, may explain age‐related stiffening.

Summary: Temperature is increasing globally, and vector-borne diseases are particularly responsive to such increases. While it is known that temperature influences mosquito life history traits, transmission models have not historically considered population-specific effects of temperature. We assessed the interaction between Culex pipiens population and temperature in New York State (NYS) and utilized novel empirical data to inform predictive models of West Nile virus (WNV) transmission. Genetically and regionally distinct populations from NYS were reared at various temperatures, and life history traits were monitored and used to inform trait-based models. Variation in Cx. pipiens life history traits and population-dependent thermal responses account for a predicted 2.9°C difference in peak transmission that is reflected in regional differences in WNV prevalence. We additionally identified genetic signatures that may contribute to distinct thermal responses. Together, these data demonstrate how population variation contributes to significant geographic variability in arbovirus transmission with changing climates.

Background: The indications for using zygomatic implantsinvolve cases with severe resorption of the maxillary arch resulting in inadequate bone volume. The case report aims to review the HIV virus and current protocols, perioperative management and the surgical approach of zygomatic implant placement in combination with traditional implants in an HIV-positive patient. Case report: A 59-year-old HIV positive male patient presents with atrophic maxillary and mandibular arches. Surgical placement of two zygomatic implants, two endosseous implants in the maxillary arch, and six endosseous implants in the mandibular arch. A reduction of a large palatal tori was also performed. The patient exhibited no complications after the surgical procedure. The hybrid prostheses were inserted post surgically without any issues. Conclusion: Zygomatic implants can be an optimal treatment option for prosthetic rehabilitation in patients with atrophic maxilla for better functionality and aesthetics. This case demonstrates the perioperative work up and placement of zygomatic implants in a medically stable HIV-positive patient with no adverse effects five months post-operation. Various surgical approaches may be utilized with excellent patient acceptance and predictable outcomes.

Abstract Deuterium metabolic imaging (DMI) is a promising tool for investigating a tumor’s biology, and eventually contribute in cancer diagnosis and prognosis. In DMI, [6,6′-2H2]-glucose is taken up and metabolized by different tissues, resulting in the formation of HDO but also in an enhanced formation of [3,3′-2H2]-lactate at the tumor site as a result of the Warburg effect. Recent studies have shown DMI’s suitability to highlight pancreatic cancer in murine models by [3,3′-2H2]-lactate formation; an important question is whether DMI can also differentiate between these tumors and pancreatitis. This differentiation is critical, as these two diseases are hard to distinguish today radiologically, but have very different prognoses requiring distinctive treatments. Recent studies have shown the limitations that hyperpolarized MRI faces when trying to distinguish these pancreatic diseases by monitoring the [1-13C1]-pyruvate→[1-13C1]-lactate conversion. In this work, we explore DMI’s capability to achieve such differentiation. Initial tests used a multi-echo (ME) SSFP sequence, to identify any metabolic differences between tumor and acute pancreatitis models that had been previously elicited very similar [1-13C1]-pyruvate→[1-13C1]-lactate conversion rates. Although ME-SSFP provides approximately 5 times greater signal-to-noise ratio (SNR) than the standard chemical shift imaging (CSI) experiment used in DMI, no lactate signal was observed in the pancreatitis model. To enhance lactate sensitivity further, we developed a new, weighted-average, CSI-SSFP approach for DMI. Weighted-average CSI-SSFP improved DMI’s SNR by another factor of 4 over ME-SSFP—a sensitivity enhancement that sufficed to evidence natural abundance 2H fat in abdominal images, something that had escaped the previous approaches even at ultrahigh (15.2 T) MRI fields. Despite these efforts to enhance DMI’s sensitivity, no lactate signal could be detected in acute pancreatitis models (n = 10; [3,3′-2H2]-lactate limit of detection

Influenza in commercial swine populations leads to reduced gain in fattening pigs and reproductive issues in sows. This literature review aims to analyze the contributions of mathematical modeling in understanding influenza transmission and control among domestic swine. Twenty-two full-text research articles from seven databases were reviewed, categorized into swine-only (n = 13), swine–avian (n = 3), and swine–human models (n = 6). Strains of influenza models were limited to H1N1 (n = 7) and H3N2 (n = 1), with many studies generalizing the disease as influenza A. Half of the studies (n = 14) considered at least one control strategy, with vaccination being the primary investigated strategy. Vaccination was shown to reduce disease prevalence in single animal cohorts. With a continuous flow of new susceptible animals, such as in farrow-to-finish farms, it was shown that influenza became endemic despite vaccination strategies such as mass or batch-to-batch vaccination. Human vaccination was shown to be effective at mitigating human-to-human influenza transmission and to reduce spillover events from pigs. Current control strategies cannot stop influenza in livestock or prevent viral reassortment in swine, so mechanistic models are crucial for developing and testing new biosecurity measures to prevent future swine pandemics.

Although toxicology uses animal models to represent real-world human health scenarios, a critical translational gap between laboratory-based studies and epidemiology remains. In this study, we aimed to understand the toxicoepigenetic effects on DNA methylation after developmental exposure to two common toxicants, the phthalate di(2-ethylhexyl) phthalate (DEHP) and the metal lead (Pb), using a translational paradigm that selected candidate genes from a mouse study and assessed them in four human birth cohorts. Data from mouse offspring developmentally exposed to DEHP, Pb, or control were used to identify genes with sex-specific sites with differential DNA methylation at postnatal day 21. Associations of human infant DNA methylation in homologous mouse genes with prenatal DEHP or Pb were examined with a meta-analysis. Differential methylation was observed on 6 cytosines (adjusted-p

ObjectiveWe sought to examine trends in diagnosed behavioral health (BH) conditions [mental health (MH) disorders or substance use disorders (SUD)] among pregnant and postpartum individuals between 2008–2020. We then explored the relationship between BH conditions and race/ethnicity, acknowledging race/ethnicity as a social construct that influences health disparities.MethodsThis study included delivering individuals, aged 15–44 years, and continuously enrolled in a single commercial health insurance plan for 1 year before and 1 year following delivery between 2008–2020. We used BH conditions as our outcome based on relevant ICD 9/10 codes documented during pregnancy or the postpartum year.ResultsIn adjusted analyses, white individuals experienced the highest rates of BH conditions, followed by Black, Hispanic, and Asian individuals, respectively. Asian individuals had the largest increase in BH rates, increasing 292%. White individuals had the smallest increase of 192%. The trend remained unchanged even after adjusting for age and Bateman comorbidity score, the trend remained unchanged.ConclusionsThe prevalence of diagnosed BH conditions among individuals in the perinatal and postpartum periods increased over time. As national efforts continue to work toward improving perinatal BH, solutions must incorporate the needs of diverse populations to avert preventable morbidity and mortality.

Cross-species comparisons using pluripotent stem cells from primates are crucial to better understand human biology, disease, and evolution. An important primate model is the Rhesus macaque (Macaca mulatta), and we reprogrammed skin fibroblasts from a male individual to generate three induced pluripotent stem cell (iPSC) lines. These cells exhibit the typical ESC-like colony morphology, express common pluripotency markers, and can differentiate into cells of the three germ layers. All generated iPSC lines can be cultured under feeder-free conditions in commercially available medium and are therefore valuable resources for cross-species comparisons.

Abstract Clostridioides difficile (C. diff.) infection (CDI) is a leading cause of hospital acquired diarrhea in North America and Europe and a major cause of morbidity and mortality. Known risk factors do not fully explain CDI susceptibility, and genetic susceptibility is suggested by the fact that some patients with colons that are colonized with C. diff. do not develop any infection while others develop severe or recurrent infections. To identify common genetic variants associated with CDI, we performed a genome-wide association analysis in 19,861 participants (1349 cases; 18,512 controls) from the Electronic Medical Records and Genomics (eMERGE) Network. Using logistic regression, we found strong evidence for genetic variation in the DRB locus of the MHC (HLA) II region that predisposes individuals to CDI (P > 1.0 × 10–14; OR 1.56). Altered transcriptional regulation in the HLA region may play a role in conferring susceptibility to this opportunistic enteric pathogen.

Diseases in the swine industry can cause significant economic and health impacts. This review examines R0 estimates for respiratory diseases in pigs, assessing variations and comparing transmission risks within and between farms. A literature search of three databases aggregated peer-reviewed research articles on swine viral respiratory diseases’ R0 values. The study focused on seven diseases: Aujeszky’s disease (AD), Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), Circovirus, Influenza A (IA), Encephalomyocarditis Virus (EV), Classical Swine Fever (CSF), and African Swine Fever (ASF). R0 values were estimated for transmission within and between herds/farms using various methods, from complex mathematical models to simple calculations. Data primarily came from disease surveillance and laboratory experiments. The median R0 for within-herd and between-herd transmission was 10 and 3.31 for AD, 2.78 and 1.14 for PRRSV, 5.9 and 0.89 for Circovirus, 1.75 and 1.6 for CSF, and 3.94 and 3.15 for ASF. For IA and EV, only within-herd R0 values were estimated at 8.65 and 1.3, respectively. Diseases with high R0 values highlight the need for prompt detection and response to outbreaks. Continuous monitoring and evaluation of pathogen transmissibility are crucial for enhancing disease surveillance and reducing the impact of livestock diseases.

Abstract Background Acute care inpatient admissions outside of psychiatric facilities have been increasingly identified as a critical touchpoint for opioid use disorder (OUD) treatment. We sought to describe non-opioid overdose hospitalizations with documented OUD and examine receipt of post-discharge outpatient buprenorphine. Methods We examined acute care hospitalizations with an OUD diagnosis in any position within US commercially-insured adults age 18–64 years (IBM MarketScan claims, 2013–2017), excluding opioid overdose diagnoses. We included individuals with ≥ 6 months of continuous enrollment prior to the index hospitalization and ≥ 10 days following discharge. We described demographic and hospitalization characteristics, including outpatient buprenorphine receipt within 10 days of discharge. Results Most (87%) hospitalizations with documented OUD did not include opioid overdose. Of 56,717 hospitalizations (49,959 individuals), 56.8% had a primary diagnosis other than OUD, 37.0% had documentation of an alcohol-related diagnosis code, and 5.8% end in a self-directed discharge. Where opioid use disorder was not the primary diagnosis, 36.5% were due to other substance use disorders, and 23.1% were due to psychiatric disorders. Of all non-overdose hospitalizations who had prescription medication insurance coverage and who were discharged to an outpatient setting (n = 49, 237), 8.8% filled an outpatient buprenorphine prescription within 10 days of discharge. Conclusions Non-overdose OUD hospitalizations often occur with substance use disorders and psychiatric disorders, and very few are followed by timely outpatient buprenorphine. Addressing the OUD treatment gap during hospitalization may include implementing medication for OUD for inpatients with a broad range of diagnoses.

Purpose: The purpose of this paper is to identify the existing discrepancy between the educational offers that encourage entrepreneurship and the specific requirements for the development of the maritime cruise industry in Constanta, Romania.Methodology: The authors conducted research on the university educational offers in Constanta, analyzed the specializations and training programs offered, and determined the directions for the training of professional skills within the analyzed faculties.Findings: The authors found that out of 22 faculties in Constanta, only 4 specializations focused on business management or administration. Additionally, there was a discrepancy between the skills and specializations of the personnel needed in cruise services according to the analysis of customers’ feedback on Alezzi Yacht, and the specializations offered by the Romanian educational environment.Research Implications/Limitations: The research findings suggest that there is a need for a better alignment between the educational programs and the specific requirements of the maritime cruise industry in Constanta, Romania. However, the research was limited to the educational programs in Constanta and did not consider the broader national or international context.Practical Implications/Limitations: The practical implications of the research suggest that there is a need for better training and education of personnel in the maritime cruise industry in Constanta, Romania. However, the practical limitations of the research include the need for further investigation and implementation of the suggested changes.Originality: The original contribution of this paper lies in the analysis of the existing discrepancy between the educational offers that encourage entrepreneurship and the specific requirements for the development of the maritime cruise industry in Constanta, Romania. Additionally, the case study of Alezzi Yacht provides a practical example of the challenges faced by the maritime tourism industry in the region. Received: 18 April 2023 Accepted: 11 June 2023 Published: 15 June 2023

Cardiac Magnetic Resonance (CMR) protocols can be lengthy and complex, which has driven the research community to develop new technologies to make these protocols more efficient and patient-friendly. Two different approaches to improving CMR have been proposed, specifically “all-in-one” CMR, where several contrasts and/or motion states are acquired simultaneously, and “real-time” CMR, in which the examination is accelerated to avoid the need for breathholding and/or cardiac gating. The goal of this two-part manuscript is to describe these two different types of emerging rapid CMR protocols. To this end, the vision of all-in-one and real-time imaging are described, along with techniques which have been devised and tested along the pathway of clinical implementation. The pros and cons of the different methods are presented, and the remaining open needs of each are detailed. Part 1 tackles the “All-in-One” approaches, and Part 2 focuses on the “Real-Time” approaches along with an overall summary of these emerging methods.

Abstract Human health is determined by the interaction of our environment with the genome, epigenome, and microbiome, which shape the transcriptomic, proteomic, and metabolomic landscape of cells and tissues. Precision environmental health is an emerging field leveraging environmental and system-level (‘omic) data to understand underlying environmental causes of disease, identify biomarkers of exposure and response, and develop new prevention and intervention strategies. In this article we provide real-life illustrations of the utility of precision environmental health approaches, identify current challenges in the field, and outline new opportunities to promote health through a precision environmental health framework.

Abstract Background The aim of this study is to gain insight into the clinical experiences and perceptions that pediatric oncology experts, conventional healthcare providers, and complementary and alternative medicine (CAM) providers in Norway, Canada, Germany, the Netherlands, and the United States have with the use of supportive care, including CAM among children and adolescents with cancer. Methods A qualitative study was conducted using semi-structured in-depth interviews (n = 22) with healthcare providers with clinical experience working with CAM and/or other supportive care among children and adolescents with cancer from five different countries. Participants were recruited through professional associations and personal networks. Systematic content analysis was used to delineate the main themes. The analysis resulted in three themes and six subthemes. Results Most participants had over 10 years of professional practice. They mostly treated children and adolescents with leukemia who suffered from adverse effects of cancer treatment, such as nausea and poor appetite. Their priorities were to identify the parents' treatment goals and help the children with their daily complaints. Some modalities frequently used were acupuncture, massage, music, and play therapy. Parents received information about supplements and diets in line with their treatment philosophies. They received education from the providers to mitigate symptoms and improve the well-being of the child. Conclusions Clinical experiences of pediatric oncology experts, conventional health care providers, and CAM providers give an understanding of how supportive care modalities, including CAM, are perceived in the field and how they can be implemented as adaptational tools to manage adverse effects and to improve the quality of life of children diagnosed with cancer and the families.

Abstract Background Per- and polyfluoroalkyl substances (PFAS) are chemicals that are resistant to degradation and ubiquitous in our environments. PFAS may impact the developing epigenome, but current human evidence is limited to assessments of total DNA methylation. We assessed associations between first trimester PFAS exposures with newborn DNA methylation, including 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC). DNA methylation mediation of associations between PFAS and birth outcomes were explored in the Michigan Mother Infant Pairs cohort. Nine PFAS were measured in maternal first trimester blood. Seven were highly detected and included for analysis: PFHxS, PFOA, PFOS, PFNA, PFDA, PFUnDA, and MeFOSAA. Bisulfite-converted cord blood DNA (n = 141) and oxidative-bisulfite-converted cord blood (n = 70) were assayed on Illumina MethylationEPIC BeadChips to measure total DNA methylation (5-mC + 5-hmC) and 5-mC/5-hmC. Correcting for multiple comparisons, beta regressions were used to assess associations between levels of PFAS and total methylation, 5-mC, or 5-hmC. Nonlinear mediation analyses were used to assess the epigenetic meditation effect between PFAS and birth outcomes. Results PFAS was significantly associated with total methylation (q

A single-cell RNA-seq analysis of placental villous tissue provides a deconvolution reference atlas of fetal and maternal placental cell types, and indicates that placental cellular heterogeneity in preeclampsia might contribute to differences in bulk gene expression.

Introduction: Although more than 300 000 children and adolescents worldwide are diagnosed with cancer yearly, little research has been conducted investigating how healthcare providers consider risk and patient safety connected with supportive care (including complementary and alternative medicine [CAM]) in this age group. This study aimed to explore how different healthcare providers perceive and evaluate risk when patients combine supportive care and conventional medicine in clinical practice and how they communicate and inform parents about the use of these modalities. Materials and Methods: In-depth semi-structured interviews were conducted with 22 healthcare providers with expertise in treating pediatric oncology patients from 5 countries. Systematic content analysis was conducted using Nvivo 1.61. Results: The analysis resulted in 3 themes and 8 subthemes. Generally, participants were cautious about implementing unproven new modalities or therapies when recommending supporting care modalities to parents of children and adolescents with cancer. The most important criterion when recommending a modality was evidence for safety based on a risk/benefit evaluation. Negative interactions with conventional medicine were avoided by using the half-life of a drug approach (the time it takes for the amount of a drug’s active substance in the body to reduce by half). For patients with severe symptoms, less invasive modalities were used (ear seeds instead of ear needling). To enhance safety, participants practiced open and egalitarian communication with parents. Conclusion: Healthcare providers reported using a variety of approaches to achieve a safe practice when parents wanted to combine supportive care and conventional cancer treatment. They emphasized that these modalities should be foremost safe and not become an extra burden for the patients. Providers highlighted patient-centered care to meet the individual’s specific health needs and desired health outcomes. A lack of national and regional standardized training programs for supportive care in pediatric oncology was considered a hazard to patient safety.

Abstract Background Physical punishment at home and in schools is widespread around the world. Systematic reviews and meta-analyses have synthesized evidence, mostly from high-income countries (HICs), showing that physical punishment relates to multiple detrimental individual outcomes. Yet, less work has been done to synthesize the evidence on the association between physical punishment at home and schools and child, adolescent, and adult outcomes in low- and middle-income countries (LMICs), where more than 90% of children live and physical punishment is most socially normative and prevalent. In this manuscript, we present a protocol for a systematic review and meta-analysis on the characteristics of the research, associations, and variation in associations, between physical punishment at home and in schools and child, adolescent, and adult outcomes in LMICs. Methods We will conduct a review of studies published in peer-reviewed journals using quantitative methods to assess the association between physical punishment in childhood and/or adolescence and individual outcomes in LMICs. We will search for studies in 10 different databases using keywords in English, Spanish, Portuguese, Arabic, and Chinese related to physical punishment. We will extract qualitative data from the studies and the statistics needed to transform all study-level effect sizes into standardized mean difference effect sizes. For the analyses, we will employ multi-level meta-analyses to use multiple effect sizes per study and leverage within-study variation as well as between study variation using moderation analysis. Besides the meta-analyses, we will also conduct a narrative synthesis of the findings. Discussion The proposed systematic review and meta-analysis will provide timely evidence to inform global research, policy, and practice on the links between physical punishment and lifelong individual outcomes. Systematic review registration PROSPERO CRD42022347346

Abstract Background The increasing number of patients surviving cancer leads to more people experiencing late and long term-effects from the disease and its treatment. Fatigue, sleep disorders, early menopause, pain, and nerve damage are commonly reported. Methods helping people to recover after cancer treatment are therefore essential. The aims of this study were threefold; (1) to determine the level of cancer patients suffering from late and long-term effects of cancer diagnosis and treatment in Norway, (2) explore complementary and alternative medicine (CAM) modalities used for managing these adversities, and (3) describe self-perceived benefits and harms of the CAM interventions. Methods The study was conducted in cooperation with the Norwegian Cancer Society (NCS) and consisted of an online cross-sectional study among members of the NCS user panel with present or previous cancer (n = 706). The study was carried out in September/October 2021 using a modified cancer-specific version of the International Questionnaire to Measure Use of Complementary and Alternative Medicine (I-CAM-Q). A total of 315 women and 153 men agreed to participate, resulting in a response rate of 67%. Results Most of the participants (83%) suffered from late and long-term effects of cancer treatment; mostly fatigue (59.2%), sleep disorder (41.5%), hot flashes (39.2%), nerve damage (polyneuropathy, 38.0%), and pain (36.6%) with a mean number of 5.1 different late and long-term effects. Late and long-term effects were positively associated with younger age and college/university education. Nearly half of the participants experiencing late and long-term effects (43%) reported having used CAM to treat these complaints. Most frequently used were self-help practices (26%) such as relaxation therapy (19%), yoga (14%) and meditation (13%), but also visits to CAM providers were reported by 22%. Herbal- and other natural remedies to treat late and long-term effects were used by 13%. A high percentage of CAM users reported self-perceived improvements of their symptoms (86% for self-help practices, 90% for visits to CAM providers). Few experienced adverse effects of the CAM treatment. Conclusion A large proportion of cancer patients suffered from a wide range of late and long-term effects of cancer diagnosis and treatment, and they use CAM to treat these complaints to a rather high degree. Relaxation therapy, yoga, meditation, massage, and acupuncture were the most frequently used therapies regardless of complaint. The therapies used are generally considered to be both safe and beneficial for the respective complaint, indicating that the participants seem to be well informed about the choices they make.

Introduction: The developing epigenome changes rapidly, potentially making it more sensitive to toxicant exposures. DNA modifications, including methylation and hydroxymethylation, are important parts of the epigenome that may be affected by environmental exposures. However, most studies do not differentiate between these two DNA modifications, possibly masking significant effects.Methods: To investigate the relationship between DNA hydroxymethylation and developmental exposure to common contaminants, a collaborative, NIEHS-sponsored consortium, TaRGET II, initiated longitudinal mouse studies of developmental exposure to human-relevant levels of the phthalate plasticizer di(2-ethylhexyl) phthalate (DEHP), and the metal lead (Pb). Exposures to 25 mg DEHP/kg of food (approximately 5 mg DEHP/kg body weight) or 32 ppm Pb-acetate in drinking water were administered to nulliparous adult female mice. Exposure began 2 weeks before breeding and continued throughout pregnancy and lactation, until offspring were 21 days old. At 5 months, perinatally exposed offspring blood and cortex tissue were collected, for a total of 25 male mice and 17 female mice (n = 5–7 per tissue and exposure). DNA was extracted and hydroxymethylation was measured using hydroxymethylated DNA immunoprecipitation sequencing (hMeDIP-seq). Differential peak and pathway analysis was conducted comparing across exposure groups, tissue types, and animal sex, using an FDR cutoff of 0.15.Results: DEHP-exposed females had two genomic regions with lower hydroxymethylation in blood and no differences in cortex hydroxymethylation. For DEHP-exposed males, ten regions in blood (six higher and four lower) and 246 regions (242 higher and four lower) and four pathways in cortex were identified. Pb-exposed females had no statistically significant differences in blood or cortex hydroxymethylation compared to controls. Pb-exposed males, however, had 385 regions (all higher) and six pathways altered in cortex, but no differential hydroxymethylation was identified in blood.Discussion: Overall, perinatal exposure to human-relevant levels of two common toxicants showed differences in adult DNA hydroxymethylation that was specific to sex, exposure type, and tissue, but male cortex was most susceptible to hydroxymethylation differences by exposure. Future assessments should focus on understanding if these findings indicate potential biomarkers of exposure or are related to functional long-term health effects.

Polygenic risk scores (PRS) based on genome-wide discoveries are promising predictors or classifiers of disease development, severity, and/or progression for common clinical outcomes. A major limitation of most risk scores is the paucity of genome-wide discoveries in diverse populations, prompting an emphasis to generate these needed data for trans-population and population-specific PRS construction. Given diverse genome-wide discoveries are just now being completed, there has been little opportunity for PRS to be evaluated in diverse populations independent from the discovery efforts. To fill this gap, we leverage here summary data from a recent genome-wide discovery study of lipid traits (HDL-C, LDL-C, triglycerides, and total cholesterol) conducted in diverse populations represented by African Americans, Hispanics, Asians, Native Hawaiians, Native Americans, and others by the Population Architecture using Genomics and Epidemiology (PAGE) Study. We constructed lipid trait PRS using PAGE Study published genetic variants and weights in an independent African American adult patient population linked to de-identified electronic health records and genotypes from the Illumina Metabochip (n = 3,254). Using multi-population lipid trait PRS, we assessed levels of association for their respective lipid traits, clinical outcomes (cardiovascular disease and type 2 diabetes), and common clinical labs. While none of the multi-population PRS were strongly associated with the tested trait or outcome, PRSLDL-Cwas nominally associated with cardiovascular disease. These data demonstrate the complexity in applying PRS to real-world clinical data even when data from multiple populations are available.

Abstract Antimicrobial resistance is a complex One Health issue that exists in both human and veterinary medicine. To mitigate this ever-growing problem, efforts have been made to develop guidelines for appropriate antimicrobial use (AMU) across sectors. In veterinary medicine, there are notable literature gaps for proper AMU in minor species. We conducted a structured narrative review covering the years of July 2006 – July 2021 to find antimicrobial treatments for common bacterial infections in exotic (birds, rodents, reptiles, and others), small flock (chickens, turkeys, and other fowl), and backyard small ruminant (sheep and goats) species. We retrieved a total of 4728 articles, of which 21 articles met the criteria for our review. Studies were grouped according to species, syndrome, and body system affected. Other data extracted included the bacterial pathogen(s), treatment (active ingredient), and geographical origin. Body systems reported included: intra-oral (n = 4), gastrointestinal (n = 1), respiratory (n = 2), reproductive (n = 1), skin (n = 3), aural (n = 1), ocular (n = 4), and other/multisystem (n = 5). By species, our search resulted in: rabbit (n = 5), rat (n = 2), guinea pig (n = 1), chinchilla (n = 1), guinea pig and chinchilla (n = 1), avian species (n = 1), psittacine birds (n = 2), loris and lorikeets (n = 1), turtles (n = 2), lizards (n = 1), goats (n = 2) and sheep (n = 2). The results of our findings identified a distinct gap in consistent antimicrobial treatment information for commonly encountered bacterial conditions within these species. There is a persisting need for clinical trials that focus on antibacterial treatment to strengthen the evidence base for AMU within exotic, small flock, and backyard small ruminant species.

Abstract Background Dealing with the symptom burden of cancer diagnosis and treatment has led parents to seek different self-management strategies including Alternative and Complementary Medicine (CAM). The aim of this study was to perform a systematic review and meta-analysis about the use and effect of CAM modalities to treat adverse effects of conventional cancer treatment among children and young adults. Methods Six scientific research databases were used to identify randomized controlled trials (RCTs) from 1990 to September 2020. Included studies investigated the use of CAM to treat cancer treatment related adverse effects in children and young adults compared to controls. Results Twenty RCTs comprising 1,069 participants were included in this review. The included studies investigated acupuncture, mind–body therapies, supplements, and vitamins for chemotherapy-induced nausea and vomiting (CINV), oral mucositis, and anxiety among children and young adults who underwent conventional cancer treatment. Seven studies (315 participants) were included in the meta-analysis. The overall effect of CAM (including acupuncture and hypnosis only) on chemotherapy-induced nausea and/or vomiting and controls was statistically significant with a standard mean difference of -0.54, 95% CI [-0.77, -0.31] I2 = 0% (p

Abstract Background Pneumonia from SARS-CoV-2 is difficult to distinguish from other viral and bacterial etiologies. Broad-spectrum antimicrobials are frequently prescribed to patients hospitalized with COVID-19 which potentially acts as a catalyst for the development of antimicrobial resistance (AMR). Objectives We conducted a systematic review and meta-analysis during the first 18 months of the pandemic to quantify the prevalence and types of resistant co-infecting organisms in patients with COVID-19 and explore differences across hospital and geographic settings. Methods We searched MEDLINE, Embase, Web of Science (BioSIS), and Scopus from November 1, 2019 to May 28, 2021 to identify relevant articles pertaining to resistant co-infections in patients with laboratory confirmed SARS-CoV-2. Patient- and study-level analyses were conducted. We calculated pooled prevalence estimates of co-infection with resistant bacterial or fungal organisms using random effects models. Stratified meta-analysis by hospital and geographic setting was also performed to elucidate any differences. Results Of 1331 articles identified, 38 met inclusion criteria. A total of 1959 unique isolates were identified with 29% (569) resistant organisms identified. Co-infection with resistant bacterial or fungal organisms ranged from 0.2 to 100% among included studies. Pooled prevalence of co-infection with resistant bacterial and fungal organisms was 24% (95% CI 8–40%; n = 25 studies: I2 = 99%) and 0.3% (95% CI 0.1–0.6%; n = 8 studies: I2 = 78%), respectively. Among multi-drug resistant organisms, methicillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa and multi-drug resistant Candida auris were most commonly reported. Stratified analyses found higher proportions of AMR outside of Europe and in ICU settings, though these results were not statistically significant. Patient-level analysis demonstrated > 50% (n = 58) mortality, whereby all but 6 patients were infected with a resistant organism. Conclusions During the first 18 months of the pandemic, AMR prevalence was high in COVID-19 patients and varied by hospital and geography although there was substantial heterogeneity. Given the variation in patient populations within these studies, clinical settings, practice patterns, and definitions of AMR, further research is warranted to quantify AMR in COVID-19 patients to improve surveillance programs, infection prevention and control practices and antimicrobial stewardship programs globally.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is spreading rapidly in Asia. This virus is transmitted by the Asian longhorned tick (Haemaphysalis longicornis), which has parthenogenetically and sexually reproducing populations. Parthenogenetic populations were found in ≥15 provinces in China and strongly correlated with the distribution of severe fever with thrombocytopenia syndrome cases. However, distribution of these cases was poorly correlated with the distribution of populations of bisexual ticks. Phylogeographic analysis suggested that the parthenogenetic population spread much faster than bisexual population because colonization is independent of sexual reproduction. A higher proportion of parthenogenetic ticks was collected from migratory birds captured at an SFTSV-endemic area, implicating the contribution to the long-range movement of these ticks in China. The SFTSV susceptibility of parthenogenetic females was similar to that of bisexual females under laboratory conditions. These results suggest that parthenogenetic Asian longhorned ticks, probably transported by migratory birds, play a major role in the rapid spread of SFTSV.

Abstract Objective The efficacy of Rhodococcus equi-specific hyperimmune plasma (HIP) is usually evaluated in vitro. Anticoagulants (AC) used for plasma collection can negatively impact bacterial replication but their effect on R. equi growth has not been evaluated. The aim of this study was to establish the effect that AC routinely used in veterinary medicine (ACD, K2EDTA, Li Heparin, and Na Citrate) have on in vitro R. equi growth. To assess this, in vitro assays commonly used to test HIP efficacy (direct effect on microorganism and macrophage infection), were performed using each AC and non-treated bacteria. Results There was no direct effect of ACD, Li Heparin or Na Citrate on R. equi growth. These AC significantly (p

The documentation of endogenous viral elements (EVEs; virus-derived genetic material integrated into the genome of a nonviral host) has offered insights into how arthropods respond to viral infection via RNA interference pathways. Small non-coding RNAs derived from EVE loci serve to direct RNAi pathways in limiting replication and infection from cognate viruses, thus benefiting the host’s fitness and, potentially, vectorial capacity. Here we use informatic approaches to analyze nine available genome sequences of hard ticks (Acari: Ixodidae; Rhipicephalus sanguineus, R. microplus, R. annulatus, Ixodes ricinus, I. persulcatus, I. scapularis, Hyalomma asiaticum, Haemaphysalis longicornis, and Dermacentor silvarum) to identify endogenous viral elements and to illustrate the shared ancestry of all elements identified. Our results highlight a broad diversity of viral taxa as having given rise to 1234 identified EVEs in ticks, with Mononegavirales (specifically Rhabdoviridae) well-represented in this subset of hard ticks. Further investigation revealed extensive adintovirus integrations in several Ixodes species, the prevalence of Bunyavirales EVEs (notably not observed in mosquitoes), and the presence of several elements similar to known emerging human and veterinary pathogens. These results will inform subsequent work on current and past associations with tick species with regard to the viruses from which their “viral fossils” are derived and may serve as a reference for quality control of various tick-omics data that may suffer from misidentification of EVEs as viral genetic material.

Several human pathogens vectored by the blacklegged tick (Ixodes scapularis Say; Acari: Ixodidae) are endemic in the state of New Jersey. Disease incidence data suggest that these conditions occur disproportionately in the northwestern portion of the state, including in the county of Hunterdon. We conducted active surveillance at three forested sites in Hunterdon County during 2020 and 2021, collecting 662 nymphal and adult I. scapularis. Ticks were tested for five pathogens by qPCR/qRT-PCR: Anaplasma phagocytophilum, Babesia microti, Borrelia burgdorferi, Borrelia miyamotoi, and Powassan virus (POWV) lineage 2. Over 2 years, 25.4% of nymphs and 58.4% of adults were found infected with at least one pathogen, with 10.6% of all ticks infected with more than one pathogen. We report substantial spatial and temporal variability of A. phagocytophilum and B. burgdorferi, with high relative abundance of the human-infective A. phagocytophilum variant Ap-ha. Notably, POWV was detected for the first time in Hunterdon, a county where human cases have not been reported. Based on comparisons with active surveillance initiatives in nearby counties, further investigation of non-entomological factors potentially influencing rates of tick-borne illness in Hunterdon is recommended.

The socioeconomics of the Anthropocene is exposing coastal regions to multiple pressures, including climate change hazards, resource degradation, urban development and inequality. Tourism is often raised as either a panacea to, or exacerbator of, such threats to ecosystems and sustainable livelihoods. To better understand the impacts of tourism on coastal areas, Scopus and Web of Science databases were searched for the top 100 cited papers on coastal tourism. Web of Science suggested ‘highly cited’ papers were also included to allow for more recent high-impact papers. Of the papers retrieved, 44 focused on the impacts of tourism. Social/cultural and environmental impacts were viewed as mostly negative, while economic impacts were viewed as mostly positive but only of actual benefit to a few. In addition, when compared with recent whole-of-sector reviews and reports it was evident that coastal tourism is increasingly a global enterprise dominated by large corporations that leverage various interests across local to transnational scales. Through this global enterprise, even the positive economic benefits identified were overshadowed by a broader system of land and property development fuelling local wealth inequity and furthering the interests of offshore beneficiaries. Only two highly cited papers discussed tourism within a broader context of integrated coastal zone management, suggesting that tourism is mostly assessed as a discrete sector within the coastal zone and peripheral to other coastal management considerations or the global tourism sector as a whole. The findings have relevance to the holistic management of coasts, coastal tourism and the achievement of sustainable development goals in a way that considers the increasing threats from coastal hazards, resource extraction and urbanisation, as well as the pervasive impacts of international business systems from local to global scales.

Abstract Background Mitral annular plane systolic excursion (MAPSE) and left ventricular (LV) early diastolic velocity (e’) are key metrics of systolic and diastolic function, but not often measured by cardiovascular magnetic resonance (CMR). Its derivation is possible with manual, precise annotation of the mitral valve (MV) insertion points along the cardiac cycle in both two and four-chamber long-axis cines, but this process is highly time-consuming, laborious, and prone to errors. A fully automated, consistent, fast, and accurate method for MV plane tracking is lacking. In this study, we propose MVnet, a deep learning approach for MV point localization and tracking capable of deriving such clinical metrics comparable to human expert-level performance, and validated it in a multi-vendor, multi-center clinical population. Methods The proposed pipeline first performs a coarse MV point annotation in a given cine accurately enough to apply an automated linear transformation task, which standardizes the size, cropping, resolution, and heart orientation, and second, tracks the MV points with high accuracy. The model was trained and evaluated on 38,854 cine images from 703 patients with diverse cardiovascular conditions, scanned on equipment from 3 main vendors, 16 centers, and 7 countries, and manually annotated by 10 observers. Agreement was assessed by the intra-class correlation coefficient (ICC) for both clinical metrics and by the distance error in the MV plane displacement. For inter-observer variability analysis, an additional pair of observers performed manual annotations in a randomly chosen set of 50 patients. Results MVnet achieved a fast segmentation (

Evaluating the populist phenomenon in a country like Romania is a complex research objective and requires an important distinction between two dimensions – effectively measuring the public’s populist predispositions, regardless of party affinities, and evaluating the ideological discourse of the main parties as well as the relationship between these ideological approaches and the populist attitudes in society. In this study, we evaluated the current state of the populist inclinations of the voting-age population in Romania, and also the ideological mechanisms that have recently stimulated these populist attitudes. We analyzed whether we can observe a rise in populist attitudes in Romania in recent years, especially in the context of the emergence of a new political force with populist and ultra-nationalist discourse. We also evaluate the evolution of this type of ideologic discourse during the last year, as well as its relation to earlier populist political discourses in Romania. We operate on the premise that parties can have populist approaches independently from the ideology they support, and also that understanding the relation between (political) discourse and populist orientation (of the public) is relevant.

Early developmental environment can influence long-term health through reprogramming of the epigenome. Human environmental epigenetics studies rely on surrogate tissues, such as blood, to assess the effects of environment on disease-relevant but inaccessible target tissues. However, the extent to which environment-induced epigenetic changes are conserved between these tissues is unclear. A better understanding of this conservation is imperative for effective design and interpretation of human environmental epigenetics studies. The Toxicant Exposures and Responses by Genomic and Epigenomic Regulators of Transcription (TaRGET II) consortium was established by the National Institute of Environmental Health Sciences to address the utility of surrogate tissues as proxies for toxicant-induced epigenetic changes in target tissues. We and others have recently reported that perinatal exposure to lead (Pb) is associated with adverse metabolic outcomes. Here, we investigated the sex-specific effects of perinatal exposure to a human environmentally relevant level of Pb on DNA methylation in paired liver and blood samples from adult mice using enhanced reduced-representation bisulphite sequencing. Although Pb exposure ceased at 3 weeks of age, we observed thousands of sex-specific differentially methylated cytosines in the blood and liver of Pb-exposed animals at 5 months of age, including 44 genomically imprinted loci. We observed significant tissue overlap in the genes mapping to differentially methylated cytosines. A small but significant subset of Pb-altered genes exhibit basal sex differences in gene expression in the mouse liver. Collectively, these data identify potential molecular targets for Pb-induced metabolic diseases, and inform the design of more robust human environmental epigenomics studies.

BackgroundExposure to prenatal bisphenol A (BPA) and Mediterranean Diet Score (MDS) has been linked to metabolic risk in child offspring. It remains unclear if independent and interactive effects persist in adolescence.MethodsWe examined prenatal BPA and MDS on adolescent offspring metabolic syndrome risk score (MRS) and 8-isoprostane (8-iso), a biomarker of oxidative stress. Data from maternal-adolescent dyads from a Mexico City cohort were utilized, including trimester-specific prenatal BPA from spot urine and MDS from food frequency questionnaires. Offspring socio-demographic data and biomarkers to estimate MRS and 8-iso were obtained during peri-adolescence.ResultsAdjusted linear regression models examined associations between trimester-specific BPA, MDS, and BPA*MDS on outcomes. Sex-stratified analyses revealed a significant association between MDS with increased 8-iso (β = 0.064, p < 0.05), and a marginal association between trimester two BPA with increased 8-iso (β = 0.237), while MDS modified the marginal association between BPA and 8-iso in females (β = 0.046). A negative, marginal association was observed between trimester two BPA and MRS (β = – 0.728), while BPA * MDS was marginally, positively associated with MRS (β = 0.152) in males.ConclusionsStudy findings indicate that trimester two prenatal BPA and maternal adherence to a Mediterranean diet may have sexually dimorphic effects on adolescent offspring oxidative stress and metabolic syndrome risk.

Background: New amino derivatives of NBD type are of high interest due to their strong fluorescence, while compounds containing a disulphide moiety are of high interest in nano-chemistry due to their easiness of attaching to noble nanoparticles. Therefore, in this work a new fluorescent derivative of NBD and cystamine was obtained. Methods: The reaction between cystamine and NBD-chloride occurs straightforwardly, and the isolated new compound was characterized by IR, UV-Vis, fluorescence, 1H- and 13C-NMR, MS, etc. Results: Structural analysis confirmed the proposed structure and highlighted the fluorescence behavior. Conclusions: A new fluorescent derivative of cystamine was obtained and characterized by different means.

Given the unprecedented environment of long duration space exploration (LDSE), success simply cannot occur without the coordinated efforts of multiple teams, both in flight and on the ground. These multiteam systems (MTSs) are needed to achieve the complex and dynamic tasks of spaceflight missions that will be longer and more uncertain than any previously experienced. Accordingly, research is limited in terms of how to best coordinate these teams and their dynamics—and in particular, how to best prepare LDSE teams to work across time and space effectively. To begin to address these critical questions systematically, qualitative data was extracted from a series of ten interviews with experts in spaceflight and long duration analog environments. Using thematic analysis techniques, we identified several consistent themes for affective, behavioral, and cognitive elements of teamwork occurring within and between teams. We examine each of these in detail, to identify the dynamics of what is currently known and where research needs to go to provide guidance for spaceflight organizations as well as others attempting to successfully implement MTSs in novel, complex environments.

Early social experience can alter epigenetic patterns and stress responses later in life. A study on wild spotted hyenas finds that maternal care and social connections after leaving the den influence DNA methylation and contribute to a developmentally plastic stress response.