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Abstract Background Preterm birth (PTB) is associated with adverse short- and long-term health. There are known racial, ethnic, and socioeconomic inequities in PTB. Because of historical de jure and modern-day de facto segregation and neighborhood divestment, neighborhoods are a source of structural racism and disenfranchisement and a potential target for policies and interventions to reduce PTB inequity. However, the role of neighborhoods on PTB, specifically among high-risk birthing people, is largely unexplored. Methods The Boston Birth Cohort is a longitudinal birth cohort of birthing people-infant dyads at a safety-net hospital in Boston, MA between 2000 and 2018. The primary outcome was preterm birth at 35 weeks or prior. The primary predictor was neighborhood defined by census tract. We used generalized linear mixed effects models to test our hypothesis that neighborhood accounts for a signficiant proportion of PTB risk among socially at-risk birthing people. Results In multilevel models, neighborhoods were a significant predictor of preterm birth, yet accounted for only 3% of the variability in outcome. In models stratified by race, individual-level factors such as prior preterm birth, nativity status, and advanced birthing person age were significant predictors of PTB. Conclusions Neighborhood is a significant, though small, predictor of preterm birth in a high-risk birthing population. These findings suggest that individual-level interventions, rather than neighborhood-level policies, may be more effective in reducing preterm birth among high-risk birthing populations.

Abstract As major terrestrial carbon sinks, forests play an important role in mitigating climate change. The relationship between the seasonal uptake of carbon and its allocation to woody biomass remains poorly understood, leaving a significant gap in our capacity to predict carbon sequestration by forests. Here, we compare the intra-annual dynamics of carbon fluxes and wood formation across the Northern hemisphere, from carbon assimilation and the formation of non-structural carbon compounds to their incorporation in woody tissues. We show temporally coupled seasonal peaks of carbon assimilation (GPP) and wood cell differentiation, while the two processes are substantially decoupled during off-peak periods. Peaks of cambial activity occur substantially earlier compared to GPP, suggesting the buffer role of non-structural carbohydrates between the processes of carbon assimilation and allocation to wood. Our findings suggest that high-resolution seasonal data of ecosystem carbon fluxes, wood formation and the associated physiological processes may reduce uncertainties in carbon source-sink relationships at different spatial scales, from stand to ecosystem levels.

Zinc deficiency is a significant global health concern among children, manifesting in various acquired and inherited conditions. This comprehensive overview of acquired and inherited zinc deficiency-related diseases in children aimed to explore the clinical presentations, diagnostic challenges, and management strategies associated with these conditions. This case series elucidates the diverse clinical manifestations of zinc deficiency in pediatric patients, ranging from dermatitis and growth retardation to immune dysregulation and neurological abnormalities, and discusses the underlying genetic mechanisms, clinical phenotypes, and therapeutic interventions. The complexity of zinc deficiency-related diseases in children underscores the need for a multidisciplinary approach involving pediatricians, dermatologists, geneticists, and nutritionists to optimize patient care and outcomes.

Abstract Objectives Poor cardiorespiratory fitness (CRF) and high body mass index (BMI) increased the risk of developing metabolic Syndrome (MetS) mostly in Caucasians. However, the sex-specific combined association of CRF and BMI on MetS considering health-related behaviors has yet to be thoroughly examined in Japanese. This study aims to investigate the sex-specific independent and combined associations of CRF and BMI with MetS in middle-aged Japanese adults. Methods 421 participants were included in this cross-sectional study. CRF was estimated using a submaximal cycle ergometer. CRF and BMI were respectively divided into three categories according to tertile distribution. MetS was diagnosed based on five risk factors: waist circumference, triglycerides, high-density lipoprotein cholesterol, blood pressure, and fasting glucose. Multivariable logistic regression models were used to estimate independent and combined association of CRF and BMI with MetS. Results Results showed that 154 (57.5%) and 70 (45.8%) of men and women had MetS, respectively. Compared to men with lower CRF or higher BMI, men with middle and higher CRF or middle and lower BMI were less likely to have MetS. Compared with ‘unfit and higher BMI’ group, ‘unfit and lower BMI’, ‘fit and higher BMI’, and ‘fit and lower BMI’ groups in men showed statistically significant decreased prevalences of MetS. However, no significant associations were found in women. Conclusions This study found significant independent and combined associations of CRF and BMI with MetS only in men, but not in women. However, prospective studies are warranted to confirm sex-specific associations of CRF and BMI with MetS.

Background: Much of the literature related to mental health focuses on identifying risk factors and predictors of poor mental health. Less of the research has a health-promoting orientation, focusing on potential sources of resilience and strength.Aims: The current study contributes to the growing field of positive psychology by investigating the potential protective role of sense of coherence (SOC) in the association between COVID-19-related worries and adverse mental health outcomes.Methods: Participants were South African undergraduate students (n = 337) who completed the SOC scale, COVID-19-related worries scale, Beck hopelessness scale, Center for Epidemiological Studies depression scale, and the trait scale of the state-trait anxiety inventory. We used the PROCESS macro for SPSS to examine the mediating role of SOC in the relationship between COVID-19-related worries and indices of mental health. The study was undertaking in the first and second waves of the COVID-19 disease outbreak in 2020.Results: T-test analyses found that women reported higher levels of depression and anxiety than men, and correlational analyses found a significant negative association between age and anxiety. After controlling for the confounding effects of age and gender, mediation analysis demonstrated that SOC had a direct and mediating effect on hopelessness, depression, and anxiety, suggesting that it is a potential protective resource. SOC is thus the pathway through which COVID-19-related worries impact mental health.Conclusion: Enhancing this resilience resource among vulnerable population groups can promote effective coping in the context of societal crises.

BackgroundOpioid use disorder (OUD) is associated with significant morbidity and mortality; however, research on physical and mental health comorbidities and health-related quality of life (HRQoL) among people taking medication for OUD (MOUD) and living in recovery residences is sparse. We investigated the prevalence of comorbidities and examined which EQ-5D-5L HRQoL dimensions are most affected by these comorbidities.MethodsData were collected from 358 residents living in 14 Texas-based recovery residences from April 2021 to June 2023. The EQ-5D-5L descriptive system comprises five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has five levels of perceived problems, dichotomized into “No problems” (level 1) and “Any problems” (levels 2–5) for analyses. Cross-sectional analyses of residents' characteristics, comorbidities (categorized as mental health disorders or association with major body systems), and EQ-5D-5L dimensions were conducted using Chi-squared or Student t-tests. Multivariable logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs).ResultsThe mean [SD] age of residents was 36.0 [8.9]. Most residents were non-Hispanic White (68.7%), male (59.7%), unemployed (66.3%), and engaged in polysubstance use (75.4%). The most frequently reported comorbidities were mental health (26.5%), respiratory (26.3%), neurological (19.3%), cardiovascular (18.2%), and musculoskeletal (17.0%) disorders. The most reported HRQoL problems were anxiety/depression (75.8%) and pain/discomfort (53.2%). In the unadjusted regression models, all comorbidities, except mental health (negative association) and digestive (no association) disorders, were positively associated with HRQoL problems. The usual activities dimension was the most affected by comorbidities, followed by mobility and pain/discomfort. Increasing age was positively associated with cardiovascular disorders (aOR = 1.06; 95% CI = 1.03–1.10), musculoskeletal disorders (aOR = 1.03; 95% CI = 1.00–1.06), mobility problems (aOR = 1.05; 95% CI = 1.01–1.09), and pain/discomfort problems (aOR = 1.02; 95% CI = 1.00–1.05). Illicit drug use was positively associated with mobility problems (aOR = 3.36; 95% CI = 1.20–9.45). Neurological (aOR = 2.71; 95% CI = 1.38–5.33) and musculoskeletal (aOR = 2.57; 95% CI = 1.25–5.29) disorders were positively associated with pain/discomfort problems. MOUD duration was negatively associated with mental health disorders (aOR = 0.14; 95% CI = 0.08–0.22) but not HRQoL.ConclusionsComorbidities significantly predict HRQoL among individuals with OUD. Our findings highlight the need for an integrated care model to treat OUD and comorbidities to sustain recovery and improve health and HRQoL.

Social media offer opportunities for companies to promote their image, but companies online also risk being denounced if their actions do not align with their words. The rise of social media bots amplifies this risk, as it becomes possible to automate such efforts to highlight corporate hypocrisy. Our experimental survey demonstrated that bots and human actors who confront a corporation touting their commitment to equality by calling out organizational pay gaps damage perceptions of the corporation, heighten anger toward them, and ultimately can elicit boycott intentions. These hypocrisy challenges are equally effective when they come from bots and user accounts. Challenges to hypocritical behavior on social media are consequential and require further exploration.

ABSTRACT Limiting the availability of transition metals at infection sites serves as a critical defense mechanism employed by the innate immune system to combat microbial infections. Pseudomonas aeruginosa exhibits a remarkable ability to thrive in zinc-deficient environments, facilitated by intricate cellular responses governed by numerous genes regulated by the zinc-responsive transcription factor Zur. Many of these genes have unknown functions, including those within the predicted PA2911-PA2914 and PA4063-PA4066 operons. A structural bioinformatics investigation revealed that PA2911-PA2914 comprises a TonB-dependent outer membrane receptor and inner membrane ABC-permeases responsible for importing metal-chelating molecules, whereas PA4063-PA4066 contains genes encoding a MacB transporter, likely involved in the export of large molecules. Molecular genetics and biochemical experiments, feeding assays, and intracellular metal content measurements support the hypothesis that PA2911-PA2914 and PA4063-PA4066 are engaged in the import and export of the pyochelin-cobalt complex, respectively. Notably, cobalt can reduce zinc demand and promote the growth of P. aeruginosa strains unable to import zinc, highlighting pyochelin-mediated cobalt import as a novel bacterial strategy to counteract zinc deficiency. These results unveil an unexpected role for pyochelin in zinc homeostasis and challenge the traditional view of this metallophore exclusively as an iron transporter.IMPORTANCEThe mechanisms underlying the remarkable ability of Pseudomonas aeruginosa to resist the zinc sequestration mechanisms implemented by the vertebrate innate immune system to control bacterial infections are still far from being fully understood. This study reveals that the Zur-regulated gene clusters PA2911-2914 and PA4063-PA4066 encode systems for the import and export of cobalt-bound pyochelin, respectively. This proves to be a useful strategy to counteract conditions of severe zinc deficiency since cobalt can replace zinc in many proteins. The discovery that pyochelin may contribute to cellular responses to zinc deficiency leads to a reevaluation of the paradigm that pyochelin is a siderophore involved exclusively in iron acquisition and suggests that this molecule has a broader role in modulating the homeostasis of multiple metals.

This article presents data collected through Computer-Assisted Web Interviewing (CAWI), conducted in Italy with the aim of exploring the Italian population's reaction to the Russian invasion of Ukraine in February 2022 and monitoring this reaction for the first six months of the attack through a six-round survey. Each round involved a representative sample of approximately 1010 (1007–1015) Italian adult citizens. Participants were asked questions about emotional reactions to the Russian invasion, coping strategies used, solidarity behaviour toward Ukrainian refugees, perceptions of refugees as a threat to the country, trust in national and international authorities to manage the international situation, and prospects for the future. Demographic data on the respondents were also collected. The survey design was developed by a research group from two universities (the University of Salento and the University of Foggia) and a European research centre, EICAP (European Institute of Cultural Analysis for Policy). The data provided in this article is a resource for researchers, public authorities, and other parties interested in surveying and studying public opinion. This dataset can be used to explore a wide range of topics, including prosocial behaviour and attitudes towards refugees in humanitarian emergencies.

Abstract A combination of evidence, based on genetic, fossil and archaeological findings, indicates that Homo sapiens spread out of Africa between ~70-60 thousand years ago (kya). However, it appears that once outside of Africa, human populations did not expand across all of Eurasia until ~45 kya. The geographic whereabouts of these early settlers in the timeframe between ~70-60 to 45 kya has been difficult to reconcile. Here we combine genetic evidence and palaeoecological models to infer the geographic location that acted as the Hub for our species during the early phases of colonisation of Eurasia. Leveraging on available genomic evidence we show that populations from the Persian Plateau carry an ancestry component that closely matches the population that settled the Hub outside Africa. With the paleoclimatic data available to date, we built ecological models showing that the Persian Plateau was suitable for human occupation and that it could sustain a larger population compared to other West Asian regions, strengthening this claim.

The Asian Palmyra palm (Borassus flabellifer L.) is an economically important tree widely distributed in the Indian subcontinent and Southeast Asia. The multifaceted uses of the Palmyra palm fruit as food, wood, and medicine, make it a viable industrial crop. It is among the most beneficial species that have economic and medicinal value. It is found to posses antiinflammatory, anti-arthritic, cytotoxic, antibacterial, analgesic, antipyretic, hypoglycemic, and anti-oxidant properties. The plant has a very close connection with the rural livelihood, and cottage and agro-based industries of Indian economy. Unfortunately, over 60% of the annual fruit yield is often lost within ten days after harvesting due to rot in storage. The value of Palmyra fruit is not yet materialized, as no Palmyra products are commercialized so far. Even though Palmyra is an economically important palm for its nutritional aspects, it is underutilized and has not received proper attention in agricultural research, since it is a very slowly growing palm and is mostly found in the wild state. Hence, this paper attempts to give a view on Palmyra fruit’s historical importance, chemistry, nutritional properties, medicinal properties, and commercialization.

Abstract Following the development of modern genome sequencing technologies, the investigation of museum osteological finds is increasingly informative and popular. Viable protocols to help preserve these collections from exceedingly invasive analyses, would allow greater access to the specimens for scientific research. The main aim of this work is to survey skeletal tissues, specifically petrous bones and roots of teeth, using infrared spectroscopy as a prescreening method to assess the bone quality for molecular analyses. This approach could overcome the major problem of identifying useful genetic material in archaeological bone collections without resorting to demanding, time consuming and expensive laboratory studies. A minimally invasive sampling of archaeological bones was developed and bone structural and compositional changes were examined, linking isotopic and genetic data to infrared spectra. The predictive model based on Infrared parameters is effective in determining the occurrence of ancient DNA (aDNA); however, the quality/quantity of aDNA cannot be determined because of the influence of environmental and local factors experienced by the examined bones during the burial period.

This article details a correction to: Autiero, S., Elwert, F., Moscatelli, C., & Pons, J. (2023). The Seven Steps: Building the DiGA Thesaurus. Journal of Open Humanities Data, 9. https://doi.org/10.5334/johd.111.

Given progressive population ageing and the increase in the number of patients with comorbidities, the management of chronic and/or hard-to-heal wounds (HHWs) nowadays represents a common problem in many clinical settings. In these cases, standard strategies may not be sufficient. Autologous grafting represent the gold standard for permanent wound closure, but is almost never realized when the skin loss is extensive/the patient is young. The grafting of homologous skin/dermal tissue procured from cadaver donors (i.e., allografting) represents the best alternative, especially when the dermal component is lost. This request supports the activities of skin bank establishments (including donor screening, skin procurement, processing, storage, and distribution) that are regulated by specific guidelines and need to continuously meet quality standard requirements. The aim of this work is to both give specific insights of all the procedures implied in allograft preparation as well as an overview of their practical application in the treatment of different HHWs. The particular characteristics of each skin/dermal allograft released by Siena Skin Bank (cryopreserved/glycerol-preserved skin/de-epidermized dermis, acellular lyophilized de-epidermized dermis/reticular dermis) are also discussed. The exemplificative series of HHWs managed in the Dermatology Department of Siena were classified according their etiology into post-traumatic, vascular (arterial/venous/mixed/lymphatic), inflammatory, surgical, and heat/chemical burns. Globally, the clinical advantages obtained include: acceleration of healing process, pain sparing, resistance to bacterial contamination, dermal regeneration (instead of scarring), and better aesthetic–functional outcome.

Colorectal cancer (CRC) is one of the most common malignancies and a relevant cause of cancer-related deaths worldwide. Dysregulation of microRNA (miRNA) expression has been associated with the development and progression of various cancers, including CRC. Among them, miR-221 emerged as an oncogenic driver, whose high expression is associated with poor patient prognosis. The present study was conceived to investigate the anti-CRC activity of miR-221 silencing based on early clinical data achieved from a first-in-human study by our group. Going back from bedside to bench, we demonstrated that LNA-i-miR-221 reduces cell viability, induces apoptosis in vitro, and impairs tumor growth in preclinical in vivo models of CRC. Importantly, we disclosed that miR-221 directly targets TP53BP2, which, together with TP53INP1, is known as a positive regulator of the TP53 apoptotic pathway. We found that (1) both these genes are overexpressed following miR-221 inhibition, (2) the strong anti-tumor activity of LNA-i-miR-221 was selectively observed on TP53 wild-type cells, and (3) this activity was reduced in the presence of the TP53-inhibitor Pifitrin-α. Our data pave the way to further investigations on TP53 functionality as a marker predictive of response to miR-221 silencing, which might be relevant for clinical applications.

Isothermal microcalorimetry (IMC) is a potent analytical method for the real-time assessment of microbial metabolic activity, which serves as an indicator of microbial viability. This approach is highly relevant to the fields of probiotics and Live Biotherapeutic Products (LBPs), offering insights into microbial viability and growth kinetics. One important characteristic of IMC is its ability to measure microbial metabolic activity separately from cellular enumeration. This is particularly useful in situations where continuous tracking of bacterial activity is challenging. The focus on metabolic activity significantly benefits both probiotic research and industrial microbiology applications. IMC’s versatility in handling different media matrices allows for the implementation of viability assessments under conditions that mirror those found in various industrial environments or biological models. In our study, we provide a proof of concept for the application of IMC in determining viability and growth dynamics and their correlation with bacterial count in probiotic organisms. Our findings reinforce the potential of IMC as a key method for process enhancement and accurate strain characterization within the probiotic sector. This supports the broader objective of refining the systematic approach and methods used during the development process, thereby providing detailed insights into probiotics and LBPs.

Specimens in natural history museums are a valuable resource for biological research, such as taxonomic, biodiversity or evolutionary studies. However, the quality of DNA and even morphological characters can decrease over time, depending on previous fixation and long-term preservation methods. In recent years, advances in DNA extraction and sequencing techniques have allowed researchers to obtain DNA from museum specimens, even when the DNA was very fragmented. Extraction methods should ideally be morphologically non-destructive, leaving diagnostic characters intact for future taxonomic studies. Here, we assess whether the whole-body extraction widely used for several taxa would be destructive for small crustaceans kept in wet collections. We extracted the DNA from over 70 small (1-3 cm) and relatively fragile shrimps collected during the last 30 years by using: i) a piece of abdominal tissue and ii) from the entire remaining body of the animal. We photographed several samples before and after the lysis, focusing on taxonomically relevant characters. Although DNA concentration was higher in the whole-body extractions, the presence of intact DNA was not correlated to the amount of lysed tissue. The resulting genomic libraries had little to no difference in yield. The taxonomically relevant characters were primarily preserved in larger specimens, whereas smaller specimens (< 1.5 cm) became too fragile to handle or were damaged. We conclude that this method must be carried out carefully in smaller crustaceans, depending on size and taxon. We advise against using it with type specimens as the advantages do not outweigh the risks. Our experiment may provide future research with quantitative and qualitative evaluations to help scientists weigh their decisions when extracting DNA from wet collection material.

Abstract Background Under- and uninsured cancer survivors have significant medical, social, and economic complexity. For these survivors, effective care coordination between oncology and primary care teams is critical for high-quality, comprehensive care. While evidence-based interventions exist to improve coordination between healthcare teams, testing implementation of these interventions for cancer survivors seen in real-world safety-net settings has been limited. This study aimed to (1) identify factors influencing implementation of a multicomponent care coordination intervention (nurse coordinator plus patient registry) focused on cancer survivors with multiple comorbidities in an integrated safety-net system and (2) identify mechanisms through which the factors impacted implementation outcomes. Methods We conducted semi-structured interviews (patients, providers, and system leaders), structured observations of primary care and oncology operations, and document analysis during intervention implementation between 2016 and 2020. The practice change model (PCM) guided data collection to identify barriers and facilitators of implementation; the PCM, Consolidated Framework for Implementation Research, and Implementation Research Logic Model guided four immersion/crystallization data analysis and synthesis cycles to identify mechanisms and assess outcomes. Implementation outcomes included appropriateness, acceptability, adoption, and penetration. Results The intervention was appropriate and acceptable to primary care and oncology teams based on reported patient needs and resources and the strength of the evidence supporting intervention components. Active and sustained partnership with system leaders facilitated these outcomes. There was limited adoption and penetration early in implementation because the study was narrowly focused on just breast and colorectal cancer patients. This created barriers to real-world practice where patients with all cancer types receive care. Over time, flexibility intentionally designed into intervention implementation facilitated adoption and penetration. Regular feedback from system partners and rapid cycles of implementation and evaluation led to real-time adaptations increasing adoption and penetration. Discussion Evidence-based interventions to coordinate care for underserved cancer survivors across oncology and primary care teams can be implemented successfully when system leaders are actively engaged and with flexibility in implementation embedded intentionally to continuously facilitate adoption and penetration across the health system.

Abstract Anomalous aortic origin of the coronary artery (AAOCA) is a rare disease associated with sudden cardiac death, usually related to physical effort in young people. Clinical routine tests fail to assess the ischemic risk, calling for novel diagnostic approaches. To this aim, some recent studies propose to assess the coronary blood flow (CBF) in AAOCA by computational simulations but they are limited by the use of data from literature retrieved from normal subjects. To overcome this limitation and obtain a reliable assessment of CBF, we developed a fully patient-specific lumped parameter model based on clinical imaging and in-vivo data retrieved during invasive coronary functional assessment of subjects with AAOCA. In such a way, we can estimate the CBF replicating the two hemodynamic conditions in-vivo analyzed. The model can mimic the effective coronary behavior with high accuracy and could be a valuable tool to quantify CBF in AAOCA. It represents the first step required to move toward a future clinical application with the aim of improving patient care. The study was registered at Clinicaltrial.gov with (ID: NCT05159791, date 2021-12-16).

Abstract Artificial actuators have been extensively studied due to their wide range of applications from soft robotics to biomedicine. Herein we introduce an autonomous bi-enzymatic system where reversible motion is triggered by the spontaneous oxidation and reduction of glucose and oxygen, respectively. This chemo-mechanical actuation is completely autonomous and does not require any external trigger to induce self-sustained motion. The device takes advantage of the asymmetric uptake and release of ions on the anisotropic surface of a conducting polymer strip, occurring during the operation of the enzymes glucose oxidase and bilirubin oxidase immobilized on its surface. Both enzymes are connected via a redox polymer at each extremity of the strip, but at the opposite faces of the polymer film. The time-asymmetric consumption of both fuels by the enzymatic reactions produces a double break of symmetry of the film, leading to autonomous actuation. An additional break of symmetry, introduced by the irreversible overoxidation of one extremity of the polymer film, leads to a crawling-type motion of the free-standing polymer film. These reactions occur in a virtually unlimited continuous loop, causing long-term autonomous actuation of the device.

Skin aging is characterized by reactive oxygen species (ROS) accumulation, principal players in triggering events associated with aging. Our recent data on the ability of an innovative poly-component formulation (KARISMA Rh Collagen® FACE: K formulation) to suppress the biomolecular events associated with oxidative stress-induced aging prompted us to deepen the mechanisms underlying the observed effects on aged human dermal fibroblasts (HDFs). Here, we evaluated K’s ability to perform a direct free radical-scavenging action and modulate anti-oxidant systems by counteracting the inflammatory process in an H2O2-induced cellular senescence model. Standard methods were used to measure scavenging capacity and enzymatic anti-oxidant system activities. Nuclear factor E2-related factor 2 (Nrf2) and nuclear factor kappa-B (NF-κB) levels were analyzed by Western blot. We assessed pro-inflammatory cytokines, matrix metalloproteinases (MMPs), and advanced glycation end-products (AGEs). Our results show that K counteracted stress-induced aging in a dose-dependent manner by exerting a direct scavenging action and increasing anti-oxidant systems, such as superoxide dismutase (SOD) and catalase (CAT) up to control values. These findings could be associated with increased phospho-Nrf2 (p-Nrf2) expression, generally reduced in aged HDFs following exposure to different concentrations of K formulation. Moreover, K formulation caused a reduction of pro-inflammatory cytokines, interleukin-1β and -6, MMP-1 and -9, and AGE levels, events related to a downregulation of p-NF-κB level. The results indicate that K formulation re-established the normal physiology of HDFs by reducing p-NF-κB expression and restoring Nrf2 activation, thus supporting its efficacious reparative and regenerative action in treating skin aging.

Ceratitis capitata, known as the Mediterranean fruit fly (Medfly), is a major dipteran pest significantly impacting fruit and vegetable farming. Currently, its control heavily relies mainly on chemical insecticides, which pose health risks and have effects on pollinators. A more sustainable and species-specific alternative strategy may be based on double-stranded RNA (dsRNA) delivery through feeding to disrupt essential functions in pest insects, which is poorly reported in dipteran species. Previous reports in Orthoptera and Coleoptera species suggested that dsRNA degradation by specific nucleases in the intestinal lumen is among the major obstacles to feeding-mediated RNAi in insects. In our study, we experimented with three-day adult feeding using a combination of dsRNA molecules that target the expression of the ATPase vital gene and two intestinal dsRNA nucleases. These dsRNA molecules were recently tested separately in two Tephritidae species, showing limited effectiveness. In contrast, by simultaneously feeding dsRNA against the CcVha68-1, CcdsRNase1, and CcdsRNase2 genes, we observed 79% mortality over seven days, which was associated with a decrease in mRNA levels of the three targeted genes. As expected, we also observed a reduction in dsRNA degradation following RNAi against nucleases. This research illustrates the potential of utilizing molecules as pesticides to achieve mortality rates in Medfly adults by targeting crucial genes and intestinal nucleases. Furthermore, it underscores the importance of exploring RNAi-based approaches for pest management.

Skin aging is influenced by intrinsic and extrinsic factors that progressively impair skin functionality over time. Investigating the skin aging process requires thorough research using innovative technologies. This review explores the use of in vitro human 3D culture models, serving as valuable alternatives to animal ones, in skin aging research. The aim is to highlight the benefits and necessity of improving the methodology in analyzing the molecular mechanisms underlying human skin aging. Traditional 2D models, including monolayers of keratinocytes, fibroblasts, or melanocytes, even if providing cost-effective and straightforward methods to study critical processes such as extracellular matrix degradation, pigmentation, and the effects of secretome on skin cells, fail to replicate the complex tissue architecture with its intricated interactions. Advanced 3D models (organoid cultures, “skin-on-chip” technologies, reconstructed human skin, and 3D bioprinting) considerably enhance the physiological relevance, enabling a more accurate representation of skin aging and its peculiar features. By reporting the advantages and limitations of 3D models, this review highlights the importance of using advanced in vitro systems to develop practical anti-aging preventive and reparative approaches and improve human translational research in this field. Further exploration of these technologies will provide new opportunities for previously unexplored knowledge on skin aging.

Domesticated animals are artificially selected to exhibit desirable traits, however not all traits of domesticated animals are the result of deliberate selection. Loss of olfactory capacity in the domesticated pig (Sus scrofa domesticus) is one example. We used whole transcriptome analysis (RNA-Seq) to compare patterns of gene expression in the olfactory mucosa of the pig and two subspecies of wild boar (Sus scrofa), and investigate candidate genes that could be responsible for the loss of olfactory capacity. We identified hundreds of genes with reductions in transcript abundance in pig relative to wild boar as well as differences between the two subspecies of wild boar. These differences were detected mainly in genes involved in the formation and motility of villi, cilia and microtubules, functions associated with olfaction. In addition, differences were found in the abundances of transcripts of genes related to immune defenses, with the highest levels in continental wild boar subspecies. Overall, the loss of olfactory capacity in pigs appears to have been accompanied by reductions in the expression of candidate genes for olfaction. These changes could have resulted from unintentional selection for reduced olfactory capacity, relaxed selection for maintaining olfactory capacity, pleiotropic effects of genes under selection, or other non-selective processes. Our findings could be a cornerstone for future researches on wild boars, pigs, feral populations, and their evolutionary trajectories, aimed to provide tools to better calibrate species management as well as guidelines for breeders.

Grapevine fanleaf virus (GFLV) (genus Nepovirus, family Secoviridae) causes fanleaf degeneration, one of the most damaging viral diseases of grapevines. Despite substantial advances at deciphering GFLV-host interactions, how this virus overcomes the host antiviral pathways of RNA silencing is poorly understood. In this study, we identified viral suppressors of RNA silencing (VSRs) encoded by GFLV, using fluorescence assays, and tested their capacity at modifying host gene expression in transgenic Nicotiana benthamiana expressing the enhanced green fluorescent protein gene (EGFP). Results revealed that GFLV RNA1-encoded protein 1A, for which a function had yet to be assigned, and protein 1BHel, a putative helicase, reverse systemic RNA silencing either individually or as a fused form (1ABHel) predicted as an intermediary product of RNA1 polyprotein proteolytic processing. The GFLV VSRs differentially altered the expression of plant host genes involved in RNA silencing, as shown by reverse transcription-quantitative PCR. In a co-infiltration assay with an EGFP hairpin construct, protein 1A upregulated NbDCL2, NbDCL4, and NbRDR6, and proteins 1BHel and 1A+1BHel upregulated NbDCL2, NbDCL4, NbAGO1, NbAGO2, and NbRDR6, while protein 1ABHel upregulated NbAGO1 and NbRDR6. In a reversal of systemic silencing assay, protein 1A upregulated NbDCL2 and NbAGO2 and protein 1ABHel upregulated NbDCL2, NbDCL4, and NbAGO1. This is the first report of VSRs encoded by a nepovirus RNA1 and of two VSRs that act either individually or as a predicted fused form to counteract the systemic antiviral host defense, suggesting that GFLV might devise a unique counterdefense strategy to interfere with various steps of the plant antiviral RNA silencing pathways during infection. [Graphic: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract Background The COVID-19 pandemic represented a global public health emergency. Existing studies support the view that vaccination and mass immunization are among the most effective means of containing the outbreak and promoting health. However, negative attitudes toward vaccination and the related vaccine hesitancy among many groups have created a significant barrier to effectively managing the health crisis. Having a valid and reliable tool to assess attitudes toward vaccination remains imperative so that factors underlying vaccine refusal can be identified and public health interventions can be facilitated. The current study examined the psychometric properties of the Vaccination Attitudes Examination Scale (VAX) in South Africa. Methods Participants (n = 322) completed the VAX. Confirmatory factor analysis and ancillary bifactor indices were used to examine the hypothesized factor structure (a total scale and four subscales) of the scale. Inter-item correlations, factor loadings, and average variance extracted were used to examine the validity of the scale. Predictive validity was examined by comparing those who had received the COVID-19 vaccine and those who had not. The reliability of the scale was examined in terms of both Cronbach’s alpha and composite reliability. Results Confirmatory factor analysis provided support for the conceptualization of the scale as consisting of a total scale and four subscales, and ancillary bifactor indices indicated that the subscales accounted for a sufficient amount of variance (44%) after the variance explained by the total scale was considered. Overall, the analysis indicated that the scale had satisfactory reliability (alpha and composite reliability = 0.70) and provided evidence for the construct, convergent, and predictive validity of the VAX. Conclusions The sound psychometric qualities of the scale, when used in a low- to middle-income country, have the potential to advance research and immunization policy within these settings and facilitate more targeted interventions to promote vaccine uptake.

Abstract Macrophages infected with Gram-negative bacteria expressing Type III secretion system (T3SS) activate the NLRC4 inflammasome, resulting in Gasdermin D (GSDMD)-dependent, but GSDME independent IL-1β secretion and pyroptosis. Here we examine inflammasome signaling in neutrophils infected with Pseudomonas aeruginosa strain PAO1 that expresses the T3SS effectors ExoS and ExoT. IL-1β secretion by neutrophils requires the T3SS needle and translocon proteins and GSDMD. In macrophages, PAO1 and mutants lacking ExoS and ExoT (ΔexoST) require NLRC4 for IL-1β secretion. While IL-1β release from ΔexoST infected neutrophils is also NLRC4-dependent, infection with PAO1 is instead NLRP3-dependent and driven by the ADP ribosyl transferase activity of ExoS. Genetic and pharmacologic approaches using MCC950 reveal that NLRP3 is also essential for bacterial killing and disease severity in a murine model of P. aeruginosa corneal infection (keratitis). Overall, these findings reveal a function for ExoS ADPRT in regulating inflammasome subtype usage in neutrophils versus macrophages and an unexpected role for NLRP3 in P. aeruginosa keratitis.

Objectives There has been a rapid shift from face-to-face to remote consultation across healthcare settings. 90% of patients with mental health conditions are cared for entirely in primary care. Remote consultation can present challenges and benefits for patients with mental health conditions. The aim of this systematic review was to collate and examine the evidence relating to remote consultation in UK primary care on the experiences of patients with mental health conditions. Methods Six major databases were searched for empirical studies published in the English language between 1 January 2010 and 21 October 2022. Studies were included where remote consultation occurred between a patient and primary care clinician. Outcomes of interest include mode of remote consultation, patient experiences and characteristics. Final included studies were assessed for quality, and results analysed with narrative synthesis. Results Six studies met the inclusion criteria, covering a range of mental health conditions and remote consultation modalities (telephone, video, online, email, text-based). Patients were overall satisfied with remote consultation, with particular benefit for certain mental health conditions or anxious patients. However, several studies found that face-to-face was the preferred method, with highlighted negatives to remote consultation, such as inflexibility of online formats. Acceptability of remote consultation is context specific and influenced by the purpose of the consultation and individual patient. Remote consultation may reduce anxiety in some patients, but is potentially less acceptable than face-to-face for relational appointments. Conclusions Acceptability of remote consultation is context dependent. There is a lack of evidence surrounding patient characteristics and access to remote consultation.

The effective management of marine ecosystems in the face of growing anthropogenic pressures requires the integration of data from different ecological components. Holistic approaches to evaluate the ecological status of marine ecosystems are still scarce, likely due to the challenge of integrating the complex information from a variety of indicators. In this study, we provided an application of a quantitative Weight-Of-Evidence (WOE) model based on the Sediqualsoft® software, combining environmental and biological data to assess ecological risk in soft-bottom habitats within Natura sites 2000 in the Northern Adriatic Sea (Mediterranean Sea). Here, the WOE approach combined three lines of evidence (LOE): chemical characterization (LOE1), ecotoxicological properties (LOE4), and benthic community status (LOE5). A separate hazard quotient was derived for each LOE prior to a weighted integration into a synthetic WOE assessment. The chemical analysis of the sediments revealed concentrations of pollutants far lower the reference limits, except for As and Hg and for polycyclic aromatic hydrocarbons which determined a ‘Slight’ to ‘Severe’ chemical hazard in coastal sites. Ecotoxicological hazard was rated as ‘Absent’ at all sampling stations, and the analysis of benthic communities indicated ‘undisturbed’ conditions for most sites. The WOE approach classified the overall ecological risk to be ‘Absent’ for offshore sites and ‘Slight’ in nearshore sites. Although results suggested a general low ecological risk, the potential for future risks is recognized, especially in coastal areas, due to well-known sediment pollution in the region. The application of the WOE approach may represent a valuable tool for managing marine protected sites, and to characterize the overall ecological status of these areas and improve conservation strategies in highly anthropized environmental contexts.

Wilson’s disease (WD) is a rare autosomal recessive disorder caused by mutations in the ATP7B gene, resulting in copper accumulation. Symptoms rarely appear before the age of 5, almost never before 3. The phenotypic variability of WD suggests the presence of modifying factors, making early diagnosis challenging. We present a case of symptomatic WD in a toddler, emphasizing the importance of considering WD in differential diagnoses and exploring genetic modifiers influencing disease onset. Clinical and laboratory assessments, including liver biopsy, were performed on a 4.2-year-old boy presenting with hypertransaminasemia and mild hepatomegaly. Histological evaluation revealed chronic hepatitis with fibrosis and severe steatosis, indicating long-standing active disease. Genetic analysis identified a missense variant and a 15-nucleotide deletion in the 5′ UTR promoter region of the ATP7B gene, confirming the WD diagnosis. Additionally, homozygosity for the HFE H63D variant was detected, with transferrin saturations at the upper limit of normal. The patient’s clinical management included a trial of D-penicillamine, discontinued due to side effects, followed by successful zinc acetate therapy. This case underscores the consideration of WD in the differential diagnosis of toddlers. The Ferenci-Leipzig score remains a valid diagnostic tool for WD even in the presence of a single ATP7B variant, although extended genetic analysis should still be considered. Normal ceruloplasmin levels do not rule out WD. Environmental, epigenetic, and genetic factors appear to influence the WD phenotype; HFE variants may act as modifiers given the link between iron and copper homeostasis, possibly explaining the early symptomatic onset in our patient.

We present a near-infrared (NIR) candidate star cluster catalog for the central kiloparsec of M82 based on new JWST NIRCam images. We identify star cluster candidates using the F250M filter, finding 1357 star cluster candidates with stellar masses >10 ^4 M _⊙ . Compared to previous optical catalogs, nearly all (87%) of the candidates we identify are new. The star cluster candidates have a median intrinsic cluster radius of ≈1 pc and stellar masses up to 10 ^6 M _⊙ . By comparing the color–color diagram to dust-free yggdrasil stellar population models, we estimate that the star cluster candidates have A _V ∼ 3−24 mag, corresponding to A _2.5 _μ _m ∼ 0.3−2.1 mag. There is still appreciable dust extinction toward these clusters into the NIR. We measure the stellar masses of the star cluster candidates, assuming ages of 0 and 8 Myr. The slope of the resulting cluster mass function is β = 1.9 ± 0.2, in excellent agreement with studies of star clusters in other galaxies.

IntroductionProbiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. From this definition, accurate enumeration of probiotic products is a necessity. Nonetheless, this definition does not specify the methods for assessing such viability. Colony forming units is the de facto gold standard for enumerating viable in probiotic products. The notion of microbial viability has been anchored in the concept of cultivability, which refers to a cell’s capacity to replicate and form colonies on agar media. However, there is a growing consensus that the term “viability” should not be exclusively tied to the ability to cultivate cells. For example, bacterial cells can exist in a Viable But Non-Culturable (VBNC) state, characterized by the maintenance of characteristics such as membrane integrity, enzymatic activity, pH gradients, and elevated levels of rRNA, despite losing the ability to form colonies.MethodsHerein we present the results of a collaborative inter-laboratory ring test for cytometric bacterial quantification. Specifically, membrane integrity fluorescence flow cytometry (FFC) method and the newer impedance flow cytometry (IFC) method have been used. Both methods interrogate single cells in solution for the presence of intact membranes. FFC exploits fluorochromes that reflect the presence or absence of an intact membrane. IFC probes membrane integrity in a label-free approach by detecting membrane-induced hindrances to the propagation of electricity.ResultsA performance ring-test and comparison design on the FFC method showed that the method is robust against the exchange of equipment, procedures, materials, and operators. After initial method optimization with assessments of rehydration medium, wake-up duration, and phase shift gating on the individual strains, the IFC method showed good agreement with the FFC results. Specifically, we tested 6 distinct species of probiotic bacteria (3 Lactobacillus and 3 Bifidobacterium strains) finding good agreement between FFC and IFC results in terms of total and live cells.DiscussionTogether, these results demonstrate that flow cytometry is a reliable, precise, and user-friendly culture-independent method for bacterial enumeration.

Abstract Background Pronectins™ are a new class of fibronectin-3-domain 14th-derived (14Fn3) antibody mimics that can be engineered as bispecific T cell engager (BTCE) to redirect immune effector cells against cancer. We describe here the in vitro and in vivo activity of a Pronectin™ AXL-targeted first-in-class bispecific T cell engager (pAXLxCD3ε) against Epithelial Ovarian Cancer (EOC). Methods pAXLxCD3ε T-cell mediated cytotoxicity was evaluated by flow cytometry and bioluminescence. pAXLxCD3ε mediated T-cell infiltration, activation and proliferation were assessed by immunofluorescence microscopy and by flow cytometry. Activity of pAXLxCD3ε was also investigated in combination with poly-ADP ribose polymerase inhibitors (PARPi). In vivo antitumor activity of pAXLxCD3ε was evaluated in immunocompromised (NSG) mice bearing intraperitoneal or subcutaneous EOC xenografts and immunologically reconstituted with human peripheral blood mononuclear cells (PBMC). Results pAXLxCD3ε induced dose-dependent cytotoxicity by activation of T lymphocytes against EOC cells, regardless of their histologic origin. The addition of PARPi to cell cultures enhanced pAXLxCD3ε cytotoxicity. Importantly, in vivo, pAXLxCD3ε was highly effective against EOC xenografts in two different NSG mouse models, by inhibiting the growth of tumor cells in ascites and subcutaneous xenografts. This effect translated into a significantly prolonged survival of treated animals. Conclusion pAXLxCD3ε is an active therapeutics against EOC cells providing a rational for its development as a novel agent in this still incurable disease. The preclinical validation of a first-in-class agent opens the way to the development of a new 14Fn3-based scaffold platform for the generation of innovative immune therapeutics against cancer.

Abstract Background Metabolic syndrome (MetS) is a cluster of atherosclerotic risk factors that increases cardiovascular risk. MetS has been associated with periodontitis, but the contribution of single MetS components and any possible sexual dimorphism in this relation remain undetermined. Methods Using the third National Health and Nutrition Examination Survey (NHANES III), we performed a nested cross-sectional study to test whether individuals aged > 30 years undergoing periodontal evaluation (population) exposed to ≥ 1 MetS component (exposure) were at increased risk of bleeding/non-bleeding periodontal diseases (outcome) compared to nonexposed individuals, propensity score matched for sex, age, race/ethnicity, and income (controls). The association between MetS components combinations and periodontal diseases was explored overall and across subgroups by sex and smoking. Periodontal health status prediction based on MetS components was assessed. Results In total, 2258 individuals (n. 1129/group) with nested clinical-demographic features were analyzed. Exposure was associated with gingival bleeding (+ 18% risk for every unitary increase in MetS components, and triple risk when all five were combined), but not with stable periodontitis; the association was specific for women, but not for men, irrespective of smoking. The only MetS feature with significant association in men was high BP with periodontitis. CRP levels significantly increased from health to disease only among exposed women. MetS components did not substantially improve the prediction of bleeding/non-bleeding periodontal disease. Conclusion The observed women-specific association of gingival bleeding with single and combined MetS components advances gender and precision periodontology. Further research is needed to validate and expand these findings.

Microplastic pollution poses an escalating concern, particularly in coastal lagoons rich in biodiversity. This study delved into the occurrence of microplastics (MPs) in Magallana gigas (formerly Crassostrea gigas) from the Orbetello and Varano coastal lagoons (Italy), also investigating the response of these filter-feeding organisms to various colors (P = pink; B = blue; W = white) of high-density polyethylene (HDPE) MP fragments. Oysters were exposed for 7 days under controlled conditions. Subsequently, the oysters underwent analysis for both MP presence and biochemical markers of oxidative stress. Diverse ingestion rates of HDPE were noted among oysters from the two lagoons, eliciting antioxidant responses and modifying baseline activity. The two-way ANOVA revealed the significant effects of treatment (control; HDPE_B; HDPE_P; HDPE_W), site, and the interaction between treatment and site on all biomarkers. Non-metric multidimensional scaling showed a divergent effect of HDPE color on biomarkers. Further investigation is warranted to elucidate the mechanisms underlying the influence of MP color, dose-dependent effects, and the long-term impacts of exposure. Comprehending these intricacies is imperative for devising effective strategies to mitigate plastic pollution and safeguard marine health.

Background. Enamel plays an essential role in protecting the underlying layers of the human tooth; therefore, preserving it is vital. This experimental study aimed to evaluate the potential ability of L. brevis to counteract the action of a demineralizing agent on dental enamel morphology and mineral composition in vitro. Methods. The sample consisted of 12 healthy human posterior teeth. The coronal portion of each tooth was subdivided into two equal parts longitudinally. The specimens were randomly divided into four groups: artificial saliva, L. brevis suspension, demineralizing agent (DA), and DA plus L. brevis. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) were used to evaluate the surface micromorphology and the mineral content, respectively. The statistical analysis was conducted using a one-way ANOVA, followed by Tukey’s post hoc test. Results. SEM analysis did not highlight significant changes in the enamel microstructure of L. brevis-treated specimens compared to the control. DA-induced damage to the enamel structure was drastically reduced when the specimens were contextually exposed to the probiotic. The treatment with DA substantially reduced the weight % of crucial enamel minerals, i.e., Ca and P. Notably, the probiotic was able to reverse the demineralization process, bringing Ca and P weight % back to basal levels, including the Ca/P ratio. Conclusions. The findings indicate that L. brevis is able to efficiently protect the dental enamel surface from the damage caused by DA and increase the enamel resistance to demineralization. Overall, L. brevis confirms its efficacy in preventing or counteracting the action of carious lesions through a novel mechanism that protects the tooth surface under a chemical challenge that mimics the caries process.

Background: In atherothrombotic acute ischemic stroke (AIS), when the atheroma breaks down, the clot can incorporate foam cells (FCs). The identification of the correct etiology is paramount for secondary stroke prevention. This study aims to evaluate the presence of the FC in the arterial clot, and to determine whether patients with FCs and patients without FCs (NFCs) had different cerebrovascular risk factors, haemato-chemical parameters, and atherosclerotic disease incidence, in order to predict the etiological diagnosis. Methods: We collected 100 clots retrieved by mechanical thrombectomy from 495 consecutive AIS patients with large vessel occlusion. An expert pathologist evaluated the FC presence by histological examination stained with hematoxylin and eosin. Results: We observed FCs in 29/100 (29%) of retrieved clots and divided the patients into two groups, with/without FCs. The two groups had similar clinical and laboratory features, with a discrepancy between the FC presence in the clot and the clinical etiological diagnosis, even if not statistically significant. Conclusions: Our study showed the presence of FCs in approximately one-third of the retrieved clots, but the identification of the clot that presumably comes from the atheromatous plaque rupture tended to disagree with the clinical diagnosis. Future studies may reveal their potential to disclose clot origin or specific patient characteristics, guiding treatment options.

An environmentally friendly and sustainable approach was adopted to produce a molecularly imprinted polymer (MIP) via electropolymerization, with remarkable electrochemical sensing properties, tested in tyrosine (tyr) detection. The 2,2′-bis(2,2′-bithiophene-5-yl)-3,3′-bithianaphtene (BT2-T4) was chosen as functional monomer and MIP electrosynthesis was carried out via cyclic voltammetry on low-volume (20 μL) screen-printed carbon electrodes (C-SPE) in ionic liquid 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ((BMIM) TFSI). An easy and rapid washing treatment allowed us to obtain the resulting MIP film, directly used for tyr electrochemical detection, carried out amperometrically. The sensor showed a linear response in the concentration range of 15–200 μM, with LOD of 1.04 µM, LOQ of 3.17 μM and good performance in selectivity, stability, and reproducibility. Tyrosine amperometric detection was also carried out in human plasma, resulting in a satisfactory recovery estimation. The work represents the first use of BT2-T4 as a functional monomer for the production of a molecularly imprinted polymer, with a green approach afforded by using a few microliters of a room temperature ionic liquid as an alternative to common organic solvents on screen-printed carbon electrodes, resulting in a valuable system that meets the green chemistry guidelines, which is today an essential criterion in both research and application field.

IntroductionThe widespread mass mortality of the noble pen shell (Pinna nobilis) has occurred in several Mediterranean countries in the past 7 years. Single-stranded RNA viruses affecting immune cells and leading to immune dysfunction have been widely reported in human and animal species. Here, we present data linking P. nobilis mass mortality events (MMEs) to hemocyte picornavirus (PV) infection. This study was performed on specimens from wild and captive populations.MethodsWe sampled P. nobilis from two regions of Spain [Catalonia (24 animals) and Murcia (four animals)] and one region in Italy [Venice (6 animals)]. Each of them were analyzed using transmission electron microscopy (TEM) to describe the morphology and self-assembly of virions. Illumina sequencing coupled to qPCR was performed to describe the identified virus and part of its genome.Results and discussionIn 100% of our samples, ultrastructure revealed the presence of a virus (20 nm diameter) capable of replicating within granulocytes and hyalinocytes, leading to the accumulation of complex vesicles of different dimensions within the cytoplasm. As the PV infection progressed, dead hemocytes, infectious exosomes, and budding of extracellular vesicles were visible, along with endocytic vesicles entering other cells. The THC (total hemocyte count) values observed in both captive (eight animals) (3.5 × 104–1.60 × 105 ml−1 cells) and wild animals (14 samples) (1.90–2.42 × 105 ml−1 cells) were lower than those reported before MMEs. Sequencing of P. nobilis (six animals) hemocyte cDNA libraries revealed the presence of two main sequences of Picornavirales, family Marnaviridae. The highest number of reads belonged to animals that exhibited active replication phases and abundant viral particles from transmission electron microscopy (TEM) observations. These sequences correspond to the genus Sogarnavirus—a picornavirus identified in the marine diatom Chaetoceros tenuissimus (named C. tenuissimus RNA virus type II). Real-time PCR performed on the two most abundant RNA viruses previously identified by in silico analysis revealed positive results only for sequences similar to the C. tenuissimus RNA virus. These results may not conclusively identify picornavirus in noble pen shell hemocytes; therefore, further study is required. Our findings suggest that picornavirus infection likely causes immunosuppression, making individuals prone to opportunistic infections, which is a potential cause for the MMEs observed in the Mediterranean.

In previous studies, problem solving appraisal has been identified as playing a key role in promoting positive psychological well-being. The Problem Solving Inventory is the most widely used measure of problem solving appraisal and consists of 32 items. The length of the instrument, however, may limit its applicability to large-scale surveys consisting of several instruments. This study investigated the possibility of reducing the number of items in the inventory using item response theory. We used the automated item selection procedure in Mokken analysis which identified 12 items as unscalable or loading on a separate scale or violating invariant item ordering. Rasch analysis, Mokken analysis, and classical test theory were then used to investigate the psychometric properties of the shorter version of the instrument. The results supported the reliability, validity, and dimensionality of the three subscales in the shortened version. The shortened version of the Problem Solving Inventory (PSI-20) and its subscales had very strong relationships with the original scale and its subscales, and the correlation of the total scale and the subscales of the shortened version with related variables was very similar to the relationships that the original scale and the subscales had with those same variables. The PSI-20 is thus beneficial in identifying changes in metacognition related to problem solving ability and can provide a basis for further intervention.

Abstract Background Multiple myeloma (MM) is a hematologic malignancy characterized by high genomic instability, and telomere dysfunction is an important cause of acquired genomic alterations. Telomeric repeat-containing RNA (TERRA) transcripts are long non-coding RNAs involved in telomere stability through the interaction with shelterin complex. Dysregulation of TERRAs has been reported across several cancer types. We recently identified a small molecule, hit 17, which stabilizes the secondary structure of TERRA. In this study, we investigated in vitro and in vivo anti-MM activities of hit 17. Methods Anti-proliferative activity of hit 17 was evaluated in different MM cell lines by cell proliferation assay, and the apoptotic process was analyzed by flow cytometry. Gene and protein expressions were detected by RT-qPCR and western blotting, respectively. Microarray analysis was used to analyze the transcriptome profile. The effect of hit 17 on telomeric structure was evaluated by chromatin immunoprecipitation. Further evaluation in vivo was proceeded upon NCI-H929 and AMO-1 xenograft models. Results TERRA G4 stabilization induced in vitro dissociation of telomeric repeat‐binding factor 2 (TRF2) from telomeres leading to the activation of ATM-dependent DNA damage response, cell cycle arrest, proliferation block, and apoptotic death in MM cell lines. In addition, up-regulation of TERRA transcription was observed upon DNA damage and TRF2 loss. Transcriptome analysis followed by gene set enrichment analysis (GSEA) confirmed the involvement of the above-mentioned processes and other pathways such as E2F, MYC, oxidative phosphorylation, and DNA repair genes as early events following hit 17-induced TERRA stabilization. Moreover, hit 17 exerted anti-tumor activity against MM xenograft models. Conclusion Our findings provide evidence that targeting TERRA by hit 17 could represent a promising strategy for a novel therapeutic approach to MM.

Pollution of the marine environment by microfibers is considered a problem for ecosystem conservation. The amount of microplastic, localization of sources, and associated ecotoxicity are well known in the literature. Wastewater from washing machines is the main source of microplastic fibers in the aquatic environment, and fabrics made from recycled plastic are widely reused. The circular economy also promotes recycling of dyed natural wool materials as a basis for making new clothing, but in this case, less research has been conducted on the behaviour and effects of recycled wool microfibers in marine ecosystems. MWool® (MW) and MWool® carded (MWc) products made from recycled wool fibers were tested in mesocosms to investigate the biodegradation of wool fibers over a 260-day period and the effects of this process on marine ecosystems in terms of microfiber inputs and the ecotoxicological effects of by-products and chemicals released during degradation. The early degradation process was associated with the loss of artificial pigments from the dyed wool, particularly pink and red, which occurred within 30–90 days of exposure. Mean release of microparticles into contact water is significantly different from control (T0, p < 0.01) at 90 days MWc (36.6 mg/L) and 180 days MW (42.9 mg/L). The biodegradation process is accompanied by swelling of wool fibers, which is associated with a significant increase in mean wool thickness (p < 0.05, 18.8 ± 2.1 µm at T0 vs. 24.0 ± 7.1 µm). In both cases, the contact water was not associated with signs of ecotoxicity for the marine species tested in this study (Phaeodactylum tricornutum, Brachionus plicatilis, and Paracentrotus lividus).

Multiple sclerosis is an autoimmune inflammatory disease that affects the central nervous system through chronic demyelination and loss of oligodendrocytes. Since the relapsing-remitting form is the most prevalent, relapse-reducing therapies are a primary choice for specialists. Universal Immune System Simulator is an agent-based model that simulates the human immune system dynamics under physiological conditions and during several diseases, including multiple sclerosis. In this work, we extended the UISS-MS disease layer by adding two new treatments, i.e., cladribine and ocrelizumab, to show that UISS-MS can be potentially used to predict the effects of any existing or newly designed treatment against multiple sclerosis. To retrospectively validate UISS-MS with ocrelizumab and cladribine, we extracted the clinical and MRI data from patients included in two clinical trials, thus creating specific cohorts of digital patients for predicting and validating the effects of the considered drugs. The obtained results mirror those of the clinical trials, demonstrating that UISS-MS can correctly simulate the mechanisms of action and outcomes of the treatments. The successful retrospective validation concurred to confirm that UISS-MS can be considered a digital twin solution to be used as a support system to inform clinical decisions and predict disease course and therapeutic response at a single patient level.

Abstract Background The prevalence of certain multidrug-resistant organisms (MDROs), especially Gram-negative bacteria, is dramatically increasing in patient care settings, including pediatric and neonatal units. However, most of the new drugs available for the treatment of MDROs have not yet been studied in children and newborns. Case report We report the clinical case of a preterm neonate, born at 31 weeks gestation + 1 day of age by emergency Cesarean Section (CS), with a bloodstream infection (BSI) due to a Verona integron-borne metallo-β-lactamase (VIM)-producing Klebsiella pneumoniae. We successfully treated the infection with cefiderocol in an off-label regimen at the following dose: loading dose 60 mg/kg and then 40 mg/kg every 8 h in extended infusion for 9 days. The baby showed a quick clinical and biochemical improvement and tolerated well the treatment. Follow-up blood cultures at 48 h after the start of cefiderocol were negative. Conclusions Antimicrobial-resistant pathogens are of increasing concern in neonatal settings. More studies in this unique population are necessary to better describe the pharmacokinetic and pharmacodynamic profile of the new drugs against MDROs, such as cefiderocol, and to define a proper effective dose.

Abstract Background Abnormal and deregulated skin wound healing associated with prolonged inflammation may result in dermal fibrosis. Since the current therapeutic strategies revealed unsatisfactory, the investigation of alternative approaches such as those based on the use of specific probiotic strains could provide promising therapeutic options. In this study, we aimed to evaluate whether the lysate from S. thermophilus could antagonize the fibrogenic effects of TGF-β1 in normal human dermal fibroblasts (NHDF). Methods NHDF were exposed to TGF-β1 to establish a fibrotic phenotype. Proliferation rate and cell number were measured using the IncuCyte® Live Cell Imager system and the trypan blue dye exclusion test. Phenoconversion markers (α-SMA and fibronectin) and collagen I levels were assessed by western blot and immunofluorescence. The mRNA levels of TGF-β1 were evaluated by RT-PCR. The Smad2/3 phosphorylation level as well as β-catenin and PPARγ expression, were assessed by western blot. The cell contractility function and migration of NHDF were studied using collagen gel retraction assay, and scratch wound healing assay, respectively. The effects of S. thermophilus lysate, alone or combined with TGF-β1, were evaluated on all of the above-listed parameters and markers associated with TGF-β1-induced fibrotic phenotype. Results Exposure to the S. thermophilus lysate significantly reduced the key mediators and events involved in the abnormal activation of myofibroblasts by TGF-β1 within the fibrotic profile. The S. thermophilus treatment significantly reduced cell proliferation, migration, and myo-differentiation. In addition, the treatment with probiotic lysate reduced the α-SMA, fibronectin, collagen-I expression levels, and affected the collagen contraction ability of activated dermal fibroblasts. Moreover, the probiotic targeted the TGF-β1 signaling, reducing Smad2/3 activation, TGF-β1 mRNA level, and β-catenin expression through the upregulation of PPARγ. Conclusion This is the first report showing that S. thermophilus lysate had a remarkable anti-fibrotic effect in TGF-β1-activated NHDF by inhibiting Smad signaling. Notably, the probiotic was able to reduce β-catenin and increase PPARγ levels. The findings support our point that S. thermophilus may help prevent or treat hypertrophic scarring and keloids.

Magnesium batteries offer several advantages over commercial lithium batteries, including predicted lower cost due to the greater abundance of Mg, and better theoretical performance. Currently, there are numerous challenges to overcome in delivering commercial Mg batteries, such as the high charge density of Mg2＋ that hinders its intercalation in and out the cathode, or strict requirements for coordination of Mg2＋. In this condensed review, we present an overview of some of the key challenges and strategies for high performance, focusing on the cathode. We highlight some promising cathode compositions, including manganese oxides, the seminal Mo6S8 that is still used to evaluate novel electrolytes and anodes, and vanadium oxides, such as H2V3O8. Correlations between structure, chemistry and performance are discussed for each composition.

The preparation of Ni-rich cathode materials is challenging due to the Ni2+ion sensitivity to oxidation during synthesis. The synthesis conditions during the manufacture of Ni-rich materials such as LiNi0.8Mn0.1Co0.1O2 (NMC811) therefore require stringent control. The co-precipitation step, applied in the synthesis of the metal hydroxide precursor, determines the secondary particle assembly formation, where it is typically desirable to produce uniform, spherical, ∼10μm-diameter structures. A stirred tank reactor is often employed to maintain a constant temperature of 60 °C and a controlled pH of between 10.5 and 11.5 in an inert atmosphere to maintain a high Ni2+/Ni3+ion ratio. This promotes the formation of an NMC hydroxide precursor (NixMnyCoz(OH)2) which is typically milled with a lithium salt and calcined to form LiNixMnyCozO2 with a layered α-NaFeO2 crystalline structure. This review outlines some of the critical synthetic parameters for the formation of spherical secondary assemblies of metal hydroxide precursors for nickel-rich layered cathodes.

Contact electrification can generate useable charge on a variety of surfaces. Here, surface charge creation when a single water droplet hits various plant leaves is investigated, including the effect of droplet characteristics and whether the plant leaf is hydrophilic or hydrophobic.