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Mia Ann Xu,1 Jasmin Choi,1 Ariadna Capasso,2 Ralph J DiClemente1 1Department of Social and Behavioral Sciences, School of Global Public Health, New York University, New York, NY, USA; 2Health Resources in Action, Boston, MA, USACorrespondence: Mia Ann Xu, Email mx489@nyu.eduBackground: Lower- and middle-income countries (LMICs) are disproportionately impacted by human papillomavirus (HPV) and would benefit from implementing the HPV vaccine. In the context of competing health priorities, utilizing scarce domestic infrastructure and human resources for HPV vaccination remains challenging for many LMICs. Given the high benefits of the HPV vaccine, the World Health Organization (WHO) is now encouraging for all countries, particularly LMICs, to introduce HPV vaccines into their routine immunization programs. Understanding the barriers and facilitators to HPV adolescent vaccine programs in LMICs may help strengthen how LMICs implement HPV vaccine programs, in turn, increasing HPV vaccine acceptance, uptake, and coverage.Objective: To identify and assess barriers and facilitators to implementing adolescent HPV vaccination programs in LMICs.Methods: This study comprised a review of literature assessing adolescent HPV vaccination in LMICs published after 2020 from a sociocultural perspective.Results: Overall, the findings showed that LMICs should prioritize increasing HPV vaccine availability and HPV vaccine knowledge, particularly focusing on cancer prevention, as knowledge reduces misinformation and increases vaccine acceptance. Evidence suggests that factors promoting HPV vaccine uptake include fostering low vaccine hesitancy, integrating HPV vaccination as a primary school routine vaccination, and vaccinating both genders. A one-dose HPV vaccine may enable many LMICs to increase vaccine acceptance, uptake, and coverage while controlling financial, infrastructure, and human resource costs.Conclusion: As HPV is one of the leading causes of death in many LMICs, implementing the HPV vaccine may be highly beneficial. Cohesive national HPV vaccine buy-in and understanding the success and challenges of prior LMIC HPV vaccine implementation is crucial to developing effective, efficient, and sustainable HPV vaccination programs.Keywords: HPV, LMICs, vaccine hesitancy, HPV cost, vaccine equity

Abstract Pharmacogenetics investigates sequence of genes that affect drug response, enabling personalized medication. This approach reduces drug-induced adverse reactions and improves clinical effectiveness, making it a crucial consideration for personalized medical care. Numerous guidelines, drawn by global consortia and scientific organizations, codify genotype-driven administration for over 120 active substances. As the scientific community acknowledges the benefits of genotype-tailored therapy over traditionally agnostic drug administration, the push for its implementation into Italian healthcare system is gaining momentum. This evolution is influenced by several factors, including the improved access to patient genotypes, the sequencing costs decrease, the growing of large-scale genetic studies, the rising popularity of direct-to-consumer pharmacogenetic tests, and the continuous improvement of pharmacogenetic guidelines. Since EMA (European Medicines Agency) and AIFA (Italian Medicines Agency) provide genotype information on drug leaflet without clear and explicit clinical indications for gene testing, the regulation of pharmacogenetic testing is a pressing matter in Italy. In this manuscript, we have reviewed how to overcome the obstacles in implementing pharmacogenetic testing in the clinical practice of the Italian healthcare system. Our particular emphasis has been on germline testing, given the absence of well-defined national directives in contrast to somatic pharmacogenetics.

Abstract Background Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. Methods In this study, 382 infants born at 24+0–27+6 weeks’ gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks’ postmenstrual age. The secondary outcomes are BPD at 36 weeks’ postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). Discussion This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0–27+6 weeks’ gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks’ postmenstrual age of life. Trial registration ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Abstract Background Respect for human rights and bioethical principles in prisons is a crucial aspect of society and is proportional to the well-being of the general population. To date, these ethical principles have been lacking in prisons and prisoners are victims of abuse with strong repercussions on their physical and mental health. Methods A systematic review was performed, through a MESH of the following words (bioethics) AND (prison), (ethics) AND (prison), (bioethics) AND (jail), (ethics) AND (jail), (bioethics) AND (penitentiary), (ethics) AND (penitentiary), (prison) AND (human rights). Inclusion and exclusion criteria were defined and after PRISMA, 17 articles were included in the systematic review. Results Of the 17 articles, most were prevalence studies (n.5) or surveys (n.4), followed by cross-sectional studies (n.3), qualitative studies (n.1), retrospective (n.1) and an explanatory sequential mixed-methods study design (n.1). In most cases, the studies associated bioethics with prisoners’ access to treatment for various pathologies such as vaccinations, tuberculosis, hepatitis, HIV, it was also found that bioethics in prisons was related to the mental health of prisoners, disability, ageing, the condition of women, the risk of suicide or with the request for end-of-life by prisoners. The results showed shortcomings in the system of maintaining bioethical principles and respect for human rights. Conclusions Prisoners, in fact, find it difficult to access care, and have an increased risk of suicide and disability. Furthermore, they are often used as improper organ donors and have constrained autonomy that also compromises their willingness to have end-of-life treatments. In conclusion, prison staff (doctors, nurses, warders, managers) must undergo continuous refresher courses to ensure compliance with ethical principles and human rights in prisons.

Fluoropyrimidines, crucial in cancer treatment, often cause toxicity concerns even at standard doses. Toxic accumulation of fluoropyrimidine metabolites, culminating in adverse effects, can stem from impaired dihydropyrimidine dehydrogenase (DPYD) enzymatic function. Emerging evidence underscores the role of single nucleotide polymorphisms (SNPs) in DPYD gene, capable of inducing DPYD activity deficiency. Consequently, DPYD genotyping’s importance is on the rise in clinical practice before initiating fluoropyrimidine treatment. Although polymerase chain reaction (PCR) followed by Sanger sequencing (SS; PCR-SS) is a prevalent method for DPYD genotyping, it may encounter limitations. In this context, there is reported a case in which a routine PCR-SS approach for genotyping DPYD SNP rs55886062 failed in a proband of African descent. The Clinical Pharmacogenetics Implementation Consortium (CPIC) categorizes the guanine (G) allele of this SNP as non-functional. The enforcement of whole genome sequencing (WGS) approach led to the identification of two adenine (A) insertions near the PCR primers annealing regions in the proband, responsible for a sequence frameshift and a genotyping error for rs55886062. These SNPs (rs145228578, 1-97981199-T-TA and rs141050810, 1-97981622-G-GA) were extremely rare in non-Finnish Europeans (0.05%) but prevalent in African populations (16%). Although limited evidence was available for these SNPs, they were catalogued as benign variants in public databases. Notably, these two SNPs exhibited a high linkage disequilibrium [LD; squared correlation coefficient (R2) = 0.98]. These findings highlighted the importance to consider the prevalence of genetic variants within diverse ethnic populations when designing primers and probes for SNP genotyping in pharmacogenetic testing. This preventive measure is essential to avoid sequence frameshifts or primer misalignments arising from SNP occurrences in the genome, which can compromise PCR-SS and lead to genotyping failures. Furthermore, this case highlights the significance of exploring alternative genotyping approaches, like WGS, when confronted with challenges associated with conventional techniques.

Background: Vigna unguiculata, belonging to the Fabaceae family, commonly known as cowpea is an important edible legume, distributed mainly across the African and Asian countries. Traditionally, the plant has an outstanding background for the management of multiple diseases, animal feeding and human consumption. Objective: This review aims to mainly focus on the traditional applications, pharmacological activities, phytochemistry as well as nutritious composition of the V. unguiculata. Methods: Data present in the literature on the V. unguiculata, were collected from major scientific databases including Science Direct, SpringerLink, Google Scholar, Medline Plus, Web of Science, PubMed and Elsevier. Results: Number of compounds have been isolated including flavonoids, steroids, alkaloids, phenolic compounds, saponins, fatty acids, tannins, carbohydrates, vitamins, amino acids, carotenoids and fibers from various parts of plant. These compounds exhibit widespread pharmacological potentials both in-vitro and in-vivo including anthelmintic, antibacterial, antinociceptive, thrombolytic, antidiabetic, hypocholestrolemic and antiatherogenic effect, antimicrobial, anti-sickling, antioxidant, anti-covid activity, anticancer and neurobehavioral activities. These compounds have strong pharmacological background and might be responsible for the traditional uses of this plant that are not investigated. Conclusion: It is concluded that V. unguiculata possessed strong pharmacological, nutritious and phytochemical potential, therefore, it is strongly recommended for additional comprehensive investigations in order to determine its clinical utility.

Summary: Few studies investigated the genetics of relapsed Wilms tumor (WT), suggesting the SIX1 gene, the microRNA processing genes, and the MYCN network as possibly involved in a relevant percentage of relapses. We investigated 28 relapsing WT patients (10 new cases and 18 cases in which the involvement of SIX and miRNAPG had been excluded) with a panel of ∼5000 genes. We identified variants affecting genes involved in DNA damage prevention and repair in 12/28 relapsing patients (42.9%), and affecting genes involved in chromatin modification and regulation in 6/28 relapsing patients (21.4%), widening the spectrum of anomalies detected in relapsed tumors. The disclosure of molecular pathways possibly underlying tumor progression might allow to use molecularly targeted therapies at relapse. Surprisingly, germline anomalies, mostly affecting DNA damage prevention and repair genes, were identified in 13/28 patients (46.4%), raising the issue of performing a genetic testing to all children presenting with a WT.

Abstract 2D MXenes find applications in several technology fields. Solution processing techniques can facilitate the integration of these materials within the technological supply chain. Here, a highly concentrated (up to 1.5 g L−1) and stable dispersion of 2D Ti3C2Tx MXene flakes is produced by an environmentally friendly liquid phase exfoliation process (LPE) in dihydrolevoglucosenone (Cyrene). The flakes preserve their elemental composition after 6 months, while those exfoliated in N‐Methyl‐2‐pyrrolidone (NMP), a commonly used solvent, undergo significant oxidation. The cytotoxicity of the MXene flakes in Cyrene and in NMP is investigated by assessing the cellular viability in a human keratinocyte (HaCaT) cell line, which is a relevant model for skin applications. The data show that the MXene flakes in Cyrene induce cytotoxic effects for a dose > 1 µg cm−2, as similarly observed for the MXene flakes in NMP. Efforts are made to overcome this by collecting the MXene flakes and redispersing them in a solution of bovine serum albumin (BSA). MXene in BSA does not affect cellular viability and cell morphology, possibly due to the formation of a protective protein corona around the individual MXene flakes. These findings illustrate an environmentally friendly strategy to produce biocompatible 2D MXene for biomedical applications.

Introduction: Peritoneal Ultrafiltration (PUF) has been proposed as an additional therapeutic option for Refractory Congestive Heart Failure (RCHF) patients. Despite promising observational studies and/or case report results, limited clinical trials data exist, and so far, PUF solutions remain only indicated for chronic kidney diseases (CKD). In this article, we describe a multicenter, randomized, controlled, unblinded, adaptive design clinical trial, about to start, investigating the effects of PolyCore™, an innovative PUF solution, in the treatment of RCHF patients. Methods: The Peritoneal Ultrafiltration in Cardiorenal Syndrome (PURE) study is a Phase II, multicenter, randomized, controlled, unblinded, adaptive design clinical trial that aims to evaluate the safety and efficacy of PUF, using PolyCore™ as the investigational solution, in the treatment of RCHF patients who present with prominent right ventricular failure due to afterload mismatch, functional tricuspid regurgitation and enlarged cava vein consequent to intravascular fluid overload. Approximately 84 patients will be randomized 1:1 either to continue with their prescribed guidelines-directed medical therapy or to add the PUF treatment on top of it. The primary objective is to evaluate if PUF treatment has an impact on the composite endpoint of the patient’s mortality or worsening of the patient’s condition such as hospitalization for cardiovascular causes, increasing the initial daily dose of loop diuretic or worsening of renal function. Statistical analysis for the primary endpoint will be standard survival analysis to estimate the failure rate at month 7 for each group via Kaplan-Meier curves. Sensitivity analysis and various secondary analyses, including a multiple events analysis, will be conducted to evaluate the robustness of the primary endpoint results. Safety will be evaluated for up to 12 months. Conclusion: The PURE Study was designed to evaluate the safety and efficacy of peritoneal ultrafiltration with PolyCore™ on top of guidelines-directed medical therapy in patients with RCHF, assuming a combined clinical endpoint of mortality or worsening patients’ condition. If successful, the treatment should allow for an improvement of the RCHF symptoms, decreasing hospitalization rate of patients. ClinicalTrials.gov Identifier: NCT03994874

The extraordinary growth of health technologies has determined an increasing interest in biobanks that represent a unique wealth for research, experimentation, and validation of new therapies. “Human” biobanks are repositories of various types of human biological samples. Through years the paradigm has shifted from spontaneous collections of biological material all over the world to institutional, organized, and well-structured forms. Imaging biobanks represent a novel field and are defined by European Society of Radiology as: “organized databases of medical images, and associated imaging biomarkers shared among multiple researchers, linked to other biorepositories”. Modern radiology and nuclear medicine can provide multiple imaging biomarkers, that express the phenotype related to certain diseases, especially in oncology. Imaging biobanks, not a mere catalogue of bioimages associated to clinical data, involve advanced computer technologies to implement the emergent field of radiomics and radiogenomics. Since Europe hosts most of the biobanks, juridical and ethical framework, with a specific referral to Italy, is analyzed. Linking imaging biobanks to traditional ones appears to be a crucial step that needs to be driven by medical imaging community under clear juridical and ethical guidelines.

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase mainly found in the focal adhesion regions of the plasma membrane and it has a crucial role in migration and the remodeling of cellular morphology. FAK is also linked to several aspects of cancer biology, from cytokine production to angiogenesis, drug resistance, invasion, and metastasis, as well as epithelial-to-mesenchymal transition. The gene locus of FAK is frequently amplified in several human tumors, thus causing FAK overexpression in several cancers. Furthermore, FAK can influence extracellular matrix production and exosome secretion through cancer-associated fibroblasts, thus it has an important role in tumor microenvironment regulation. Although the role of FAK in solid tumors is well known, its importance in onco-hematological diseases remains poorly explored. This review collects studies related to FAK significance in onco-hematological diseases and their microenvironments. Overall, the importance of FAK in blood tumors is increasingly evident, but further research is required to confirm it as a new therapeutic target in hematological contexts.

Background: Updated epidemiologic data are important for defining effective public health strategies for pediatric food allergy (FA). Objective: The Epidemiology of Paediatric Italian Food Allergy (EPIFA) study was designed to investigate the epidemiology of pediatric FA in one of the most heavily populated Italian regions. Methods: A retrospective cohort study was performed in collaboration with family pediatricians aimed at investigating the epidemiology of Italian pediatric FA during 2009 to 2021. Family pediatricians in the Campania region were invited to use the Google Forms platform for online compilation of data forms. Data forms were reviewed by experienced pediatric allergists at the coordinating center. Results: A total population of 105,151 subjects (aged 0-14 years) was screened during the study period. Data from 752 FA patients were evaluated. A progressive increase in FA incidence and prevalence was observed from 2009 to 2021, with a relative increase up to 34% and 113.6%, respectively, at the end of study period. The relative increase in FA prevalence was higher in the 0-3-year-old age group in the same study period (+120.8%). The most frequent allergens were cow’s milk, hen’s egg, and nuts. Conclusion: The results of the EPIFA study showed an increase in pediatric FA incidence and prevalence from 2009 to 2021 in Italy. These results underline the necessity of new effective strategies for preventing and managing these conditions.

Este artículo analiza una acción performática de la organización de derecha argentina Jóvenes Republicanos (jr). La elección del caso, que condensa rasgos de una categoría más amplia de fenómenos similares, permite testear el funcionamiento de las categorías teóricas y analíticas que estructuran nuestro argumento y contribuye a la caracterización del fenómeno de los movimientos de derecha contemporáneos. El análisis de caso se hará desde un abordaje transdisciplinar que asocia la teoría sociopolítica, los estudios sociales del arte y la performance, y los análisis sobre la mediatización de las sociedades contemporáneas. El propósito es contribuir al análisis de un fenómeno extendido en la vida pública argentina: el de las acciones performáticas realizadas en el marco de acciones contenciosas, considerando su estatuto polivalente: incorporan lenguajes estéticos, cuestionan el valor de lo común y disputan el direccionamiento de la atención pública, política y mediática. Este tipo de performance, cuando adopta una estructura constelar, se convierte en un discurso de potencia ubicua, con capacidad de circular por superficies mediatizadas y trascender el aquí y ahora situado original.

IntroductionFrench bulldogs can be affected by several neurological diseases, with myelopathies representing the most frequent cause of neurological signs. Studies focusing on the epidemiology of cervical diseases in this breed are lacking. This study aims to describe the prevalence of neurological pathologies responsible for cervical pain and/or signs of cervical myelopathy, assuming that intervertebral disc herniation represents the most common disease; a second aim was to evaluate how often different pathologies coexist in this spinal region in French bulldogs.Materials and methodsA retrospective analysis of medical records from the database of a single referral center (AniCura I Portoni Rossi Veterinary Hospital—Zola Predosa, Bologna, Italy) was performed, including French bulldogs presented for neck pain and/or neurological deficits consistent with cervical myelopathy. Clinical and imaging data were reviewed and used as inclusion criteria. Based on the number of MRI-diagnosed diseases, the eligible dogs were divided into three groups.ResultsOne hundred five French bulldogs met the inclusion criteria. The most commonly diagnosed condition was an intervertebral disc herniation (66.9%), followed by C2 idiopathic hypertrophic ganglioneuritis (15.1%), cervical syringomyelia (11.5%), congenital osseous malformations (1.4%), spinal arachnoid diverticula (1.4%), neoplasms (1.4%), steroid-responsive meningitis-arteritis (0.7%), traumatic vertebral fractures (0.7%), and other (0.7%). For the vast majority of dogs (75/105) a single pathology was diagnosed, with intervertebral disc herniations accounting for 86.7% of cases, involving C3–C4 IVD most commonly. In the remaining 30 dogs, two or three different and concurrent diseases were detected. Among these 30 dogs, intervertebral disc herniations still remained the most diagnosed condition, in combination with C2 idiopathic hypertrophic ganglioneuritis and syringomyelia in 19 and seven cases, respectively.ConclusionThe results of this study highlight that different pathologies can affect the cervical spinal cord in French bulldogs, with intervertebral disc herniations representing the most frequent condition, as previously described in the veterinary literature. In almost a third of cases, different pathologies can coexist at the cervical level. However, for cases in which different pathologies are present at the same time, it is not always possible to clearly establish their clinical significance.

Summary: Inherited retinal diseases (IRDs) are a group of rare monogenic diseases with high genetic heterogeneity (pathogenic variants identified in over 280 causative genes). The genetic diagnostic rate for IRDs is around 60%, mainly thanks to the routine application of next-generation sequencing (NGS) approaches such as extensive gene panels or whole exome analyses. Whole-genome sequencing (WGS) has been reported to improve this diagnostic rate by revealing elusive variants, such as structural variants (SVs) and deep intronic variants (DIVs).We performed WGS on 33 unsolved cases with suspected autosomal recessive IRD, aiming to identify causative genetic variants in non-coding regions or to detect SVs that were unexplored in the initial screening. Most of the selected cases (30 of 33, 90.9%) carried monoallelic pathogenic variants in genes associated with their clinical presentation, hence we first analyzed the non-coding regions of these candidate genes. Whenever additional pathogenic variants were not identified with this approach, we extended the search for SVs and DIVs to all IRD-associated genes.Overall, we identified the missing causative variants in 11 patients (11 of 33, 33.3%). These included three DIVs in ABCA4, CEP290 and RPGRIP1; one non-canonical splice site (NCSS) variant in PROM1 and three SVs (large deletions) in EYS, PCDH15 and USH2A. For the previously unreported DIV in CEP290 and for the NCCS variant in PROM1, we confirmed the effect on splicing by reverse transcription (RT)-PCR on patient-derived RNA.This study demonstrates the power and clinical utility of WGS as an all-in-one test to identify disease-causing variants missed by standard NGS diagnostic methodologies.

During the last decades, non-destructive investigation approaches have played an essential role in preserving structural integrity, capacity, and finding early defects in reinforced concrete (RC) heritage affected by time-dependent degradation. One of the most widespread structural RC damages belongs to corrosion phenomena. Electro-chemical approaches stand out among the non-destructive techniques presently available for identifying corrosive problems in-situ. The latter gives some knowledge in terms of physical quantities aiming to evaluate structural conditions by collecting indirect measures. Nevertheless, results are correlated to strong interpretative scale codes, which may not always provide appropriate interpretation of the defect's identity. In the paper a probabilistic degradation model, based on a statistical interpretation of the in situ electro-chemical measurements, has been proposed with the aim to give a contribution for structural diagnosis. Finally, results are validated through structural visual inspection.

International Guidelines as well as Cancer Associations recommend a multidisciplinary approach to lung cancer care. A multidisciplinary team (MDT) can significantly improve treatment decision-making and patient coordination by putting different physicians and other health professionals “in the same room”, who collectively decide upon the best possible treatment. However, this is not a panacea for cancer treatment. The impact of multidisciplinary care (MDC) on patient outcomes is not univocal, while the effective functioning of the MDT depends on many factors. This review presents the available MDT literature with an emphasis on the key factors that characterize high-quality patient care in lung cancer. The study was conducted with a bibliographic search using different electronic databases (PubMed Central, Scopus, Google Scholar, and Google) referring to multidisciplinary cancer care settings. Many key elements appear consolidated, while others emerge as prevalent and actual, especially those related to visible barriers which work across geographic, organizational, and disciplinary boundaries. MDTs must be sustained by strategic management, structured within the entity, and cannot be managed as a separate care process. Furthermore, they need to coordinate with other teams (within and outside the organization) and join with the broad range of services delivered by multiple providers at various points of the cancer journey or within the system, with the vision of integrated care.

African American women have a higher likelihood of experiencing lifetime trauma compared to other racial/ethnic groups. Trauma exposure may be associated with higher substance misuse and greater adverse sexual and mental health outcomes. This study expands upon previous empirical findings to characterize the effect of trauma history on substance use, sexual health, and mental health among young African American women. This study included 560 African American women aged 18–24 years in Atlanta, Georgia. Trauma history was defined as having ever experienced a traumatic event based on the Traumatic Events Screening Inventory (TESI). Relative to women not reporting a trauma history and controlling for age, education, and employment, women who experienced trauma were over 2.5 and 2.3 times, respectively, more likely to report alcohol misuse and marijuana misuse. They were 3.0 times more likely to experience peer normative pressure for substance use. Women who experienced trauma were 2.1 times more likely to have multiple sex partners, 2.9 times more likely to have peer norms for risky sex, 1.8 times more likely to perceive barriers to using condoms with sex partners, 2.1 times more likely to report lower communication frequency about sex, 2.0 times more likely to report lower self-efficacy for refusing sex, and 1.9 times more likely to report less relationship control. Women with a trauma history were also 5.0 times more likely to have experienced intimate partner violence, 2.1 times more likely to report high depression symptomatology, 4.0 times more likely to report high overall stress, 3.2 times more likely to have worse coping skills, and 1.8 times more likely to have poor emotional regulation. Findings suggest that trauma history may increase myriad adverse psychosocial health outcomes. Screening for trauma history may help inform the provision of services. Intensified TESI screenings may help identify a history of trauma and assist in identifying adverse health outcomes.

Objectives: To describe how SARS-CoV-2 infection at the time of delivery affected maternal and neonatal outcomes across four major waves of the COVID-19 pandemic in Italy. Methods: This is a large, prospective, nationwide cohort study collecting maternal and neonatal data in case of maternal peripartum SARS-CoV-2 infection between February 2020 and March 2022. Data were stratified across the four observed pandemic waves. Results: Among 5201 COVID-19-positive mothers, the risk of being symptomatic at delivery was significantly higher in the first and third waves (20.8-20.8%) than in the second and fourth (13.2-12.2%). Among their 5284 neonates, the risk of prematurity (gestational age

Abstract The Neolithic communities of Eastern Sudan combined intensive pastoralism with plant exploitation as their main subsistence strategies. However, to date, it remains unclear which plant species were part of the human diet during the Neolithic. This contribution presents direct data on plant consumption in Eastern Sudan from the Early to Late Neolithic, obtained through the analysis of microdebris inclusions in the dental calculus of 37 individuals, integrated by dentoalveolar pathology analysis of 78 individuals, from the sites UA53 (4th millennium BCE) and Mahal Teglinos (3rd–2nd millennium BCE), located in the Gash Delta/Kassala region. Dental calculus inclusions indicate a diverse intake of cereals, legumes, and tubers during the Middle Neolithic, thus supporting the hypothesis of high reliance on plant resources. Dentoalveolar pathologies, possibly related to the consumption of carbohydrate-rich foods, have also been recorded. For the Late Neolithic, consistent with the shift towards aridity that occurred in the Middle/Late Holocene, dental calculus exclusively indicates the exploitation of sorghum and tubers—species well adapted to arid conditions—showing how the Neolithic communities modified their subsistence in response to environmental changes. Evidence of plant processing techniques, such as cooking/heating, was also revealed from the dental calculus analysis.

Abstract Background Neuroblastoma (NB) represents the most frequent and aggressive form of extracranial solid tumor of infants. Although the overall survival of patients with NB has improved in the last years, more than 50% of high-risk patients still undergo a relapse. Thus, in the era of precision/personalized medicine, the need for high-risk NB patient-specific therapies is urgent. Methods Within the PeRsonalizEd Medicine (PREME) program, patient-derived NB tumors and bone marrow (BM)-infiltrating NB cells, derived from either iliac crests or tumor bone lesions, underwent to histological and to flow cytometry immunophenotyping, respectively. BM samples containing a NB cells infiltration from 1 to 50 percent, underwent to a subsequent NB cells enrichment using immune-magnetic manipulation. Then, NB samples were used for the identification of actionable targets and for the generation of 3D/tumor-spheres and Patient-Derived Xenografts (PDX) and Cell PDX (CPDX) preclinical models. Results Eighty-four percent of NB-patients showed potentially therapeutically targetable somatic alterations (including point mutations, copy number variations and mRNA over-expression). Sixty-six percent of samples showed alterations, graded as “very high priority”, that are validated to be directly targetable by an approved drug or an investigational agent. A molecular targeted therapy was applied for four patients, while a genetic counseling was suggested to two patients having one pathogenic germline variant in known cancer predisposition genes. Out of eleven samples implanted in mice, five gave rise to (C)PDX, all preserved in a local PDX Bio-bank. Interestingly, comparing all molecular alterations and histological and immunophenotypic features among the original patient’s tumors and PDX/CPDX up to second generation, a high grade of similarity was observed. Notably, also 3D models conserved immunophenotypic features and molecular alterations of the original tumors. Conclusions PREME confirms the possibility of identifying targetable genomic alterations in NB, indeed, a molecular targeted therapy was applied to four NB patients. PREME paves the way to the creation of clinically relevant repositories of faithful patient-derived (C)PDX and 3D models, on which testing precision, NB standard-of-care and experimental medicines.

Abstract Introduction Benign tracheobronchial stenosis is a abnormal tracheal lumen narrowing that may incur progressive dyspnea and life-threatening hypoxemia. There is no consensus on which patients should be treated with endoscopic or surgical method. This study investigates the outcomes of bronchoscopic dilatation in the treatment of benign tracheal stenosis using a device equipped with a blade to cut the stenotic lesions with dense fibrosis. Materials and methods The procedure was carried out in an operating room under general anesthesia. All patients were intubated with a Rigid Bronchoscope (RB) placed just above the stenosis. Through Rigid Bronchoscopy combined modalities were used as needed: radial incisions of the mucosal stenosis with blade at the levels of 4, 8 and 12 o’clock, with back and forth movements, then the stenotic area was dilated more easily with a rigid bronchoscope. Dilatation was performed by passing the RB of increasing diameter through stenotic areas and then Balloon dilatation of increasing diameter. There were no complications during the procedure. Result We conducted an observational, retrospective, single-centre study in the Thoracic Surgery Unit of the University of ‘Luigi Vanvitelli’ of Naples from November 2011 to September 2021. We included all consecutive patients with benign tracheal stenosis inoperable. During the study period, 113 patients were referred to our department with benign tracheal stenosis inoperable. 61 patients were treated with the blade. During the follow-up, a recurrence of the stenosis was observed in 8 patients in the first month and in 4 patients in the third month. Instead in the patients treated with the use of laser (52 patients), during the follow-up a recurrence was observed in 16 patients in the first month and in 6 patients in the third month; no patient relapsed after 6 months and after 1 year. Long term successful bronchoscopic management with blade was attained by 99% in simple and 93% in mixed stenosis and in complex type stenosis. Conclusion Our study underlines the importance of the use of the blade in bronchoscopic treatment as a valid conservative approach in the management of patients with inoperable benign tracheal stenosis as an alternative to the use of the laser, reducing the abnormal inflammatory reaction in order to limit recurrences.

Abstract High-quality optical ring resonators can confine light in a small volume and store it for millions of roundtrips. They have enabled the dramatic size reduction from laboratory scale to chip level of optical filters, modulators, frequency converters, and frequency comb generators in the visible and the near-infrared. The mid-infrared spectral region (3−12 μm), as important as it is for molecular gas sensing and spectroscopy, lags behind in development of integrated photonic components. Here we demonstrate the integration of mid-infrared ring resonators and directional couplers, incorporating a quantum cascade active region in the waveguide core. It enables electrical control of the resonant frequency, its quality factor, the coupling regime and the coupling coefficient. We show that one device, depending on its operating point, can act as a tunable filter, a nonlinear frequency converter, or a frequency comb generator. These concepts extend to the integration of multiple active resonators and waveguides in arbitrary configurations, thus allowing the implementation of purpose-specific mid-infrared active photonic integrated circuits for spectroscopy, communication, and microwave generation.

This study refers to the intricate world of Acinetobacter baumannii, a resilient pathogenic bacterium notorious for its propensity at antibiotic resistance in nosocomial infections. Expanding upon previous findings that emphasised the bifunctional enzyme PaaY, revealing unexpected γ-carbonic anhydrase (CA) activity, our research focuses on a different class of CA identified within the A. baumannii genome, the β-CA, designated as 𝛽-AbauCA (also indicated as CanB), which plays a crucial role in the resistance mechanism mediated by AmpC beta-lactamase. Here, we cloned, expressed, and purified the recombinant 𝛽-AbauCA, unveiling its distinctive kinetic properties and inhibition profile with inorganic anions (classical CA inhibitors). The exploration of 𝛽-AbauCA not only enhances our understanding of the CA repertoire of A. baumannii but also establishes a foundation for targeted therapeutic interventions against this resilient pathogen, promising advancements in combating its adaptability and antibiotic resistance.

Toxoplasmosis, induced by the intracellular parasite Toxoplasma gondii, holds considerable implications for global health. While treatment options primarily focusing on folate pathway enzymes have notable limitations, current research endeavours concentrate on pinpointing specific metabolic pathways vital for parasite survival. Carbonic anhydrases (CAs, EC 4.2.1.1) have emerged as potential drug targets due to their role in fundamental reactions critical for various protozoan metabolic processes. Within T. gondii, the Carbonic Anhydrase-Related Protein (TgCA_RP) plays a pivotal role in rhoptry biogenesis. Notably, α-CA (TcCA) from another protozoan, Trypanosoma cruzi, exhibited considerable susceptibility to classical CA inhibitors (CAIs) such as anions, sulphonamides, thiols, and hydroxamates. Here, the recombinant DNA technology was employed to synthesise and clone the identified gene in the T. gondii genome, which encodes an α-CA protein (Tg_CA), with the purpose of heterologously overexpressing its corresponding protein. Tg_CA kinetic constants were determined, and its inhibition patterns explored with inorganic metal-complexing compounds, which are relevant for rational compound design. The significance of this study lies in the potential development of innovative therapeutic strategies that disrupt the vital metabolic pathways crucial for T. gondii survival and virulence. This research may lead to the development of targeted treatments, offering new approaches to manage toxoplasmosis.

Background: Cardiac remodeling is an adverse phenomenon linked to heart failure (HF) progression. Cardiac remodeling could represent the real therapeutic goal in the treatment of patients with HF and reduced ejection fraction (HFrEF), being potentially reversed through different pharmacotherapies. Currently, there are well-established drugs such as ACEi/ARBs and β-blockers with anti-remodeling effects. More recently, ARNI effects on cardiac remodeling were also demonstrated; additional potential benefits of gliflozins remain non clearly demonstrated. Aim of study: To evaluate possible changes in cardiac remodeling in patients with HFrEF/HFmrEF in treatment with ARNI or ARNI plus SGLT2i and the potential benefit on cardiac remodeling of adding SGLT2i to ARNI. Methods: Between June 2021 and August 2023, 100 consecutive patients with HFrEF/HFmrEF underwent conventional and advanced echocardiography (TDI, 2DSTE): patients were therefore divided into three groups according to therapy with neither ARNI nor SGLT2i, just ARNI or both. After 3 months, all patients underwent echocardiographic follow-up. Results: After a 3 months of therapy, significant improvements were observed for LVEF, LVEDD, LVEDV, LVESV, LV mass, E/e’, LV GLS, TAPSE (ANOVA p

The case concerns the alleged failure by the resisting administration to fulfill obligations arising from the contract and employment relationship, as well as the violation of safety regulations leading to the workplace accident reported by an Airforce Sergeant. Following the accident, the soldier complains of developing barotraumatic hearing loss with tinnitus and reactive post-traumatic stress disorder to the traumatic event. The case provides an opportunity to analyze the relevance of forensic medical assessment and its integration with psychodiagnostic examination for the correct nosographic classification aimed at evaluating and quantifying biological damage.

Multiple federal and state agencies provide assistance to qualified agricultural producers following a natural disaster, such as a hurricane. However, the programs change over time, and many producers are not aware of the programs available. The purpose of this publication is to list and briefly describe disaster assistance resources available to agricultural producers in Florida after Hurricane Idalia. To the extent that some information remains the same, this publication could provide guidance to Extension agents, nongovernmental organizations, and producers impacted by future hurricanes. The information was compiled from websites, government documents, and discussions with government agency representatives following Hurricane Idalia.

Sex differences are consistently identified in determining the prevalence, manifestation, and response to therapies in several systemic disorders, including those affecting the cardiovascular (CV), skeletal muscle, and nervous system. Interestingly, such differences are often more noticeable as we age. For example, premenopausal women experience a lower risk of CV disease than men of the same age. While at an advanced age, with menopause, the risk of cardiovascular diseases and adverse outcomes increases exponentially in women, exceeding that of men. However, this effect appears to be reversed in diseases such as pulmonary hypertension, where women are up to seven times more likely than men to develop an idiopathic form of the disease with symptoms developing ten years earlier than their male counterparts. Explaining this is a complex question. However, several factors and mechanisms have been identified in recent decades, including a role for sex hormones, particularly estrogens and their related receptors. Furthermore, an emerging role in these sex differences has also been suggested for β-adrenergic receptors (βARs), which are essential regulators of mammalian physiology. It has in fact been shown that βARs interact with estrogen receptors (ER), providing further demonstration of their involvement in determining sexual differences.Based on these premises, this review article focused on the β3AR subtype, which shows important activities in adipose tissue but with new and interesting roles in regulating the function of cardiomyocytes and vascular cells. In detail, we examined how β3AR and ER signaling are intertwined and whether there would be sex- and age-dependent specific effects of these receptor systems.

The impact of common and rare variants in COVID-19 host genetics has been widely studied. In particular, in Fallerini et al. (Human genetics, 2022, 141, 147–173), common and rare variants were used to define an interpretable machine learning model for predicting COVID-19 severity. First, variants were converted into sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. After that, the Boolean features, selected by these logistic models, were combined into an Integrated PolyGenic Score (IPGS), which offers a very simple description of the contribution of host genetics in COVID-19 severity.. IPGS leads to an accuracy of 55%–60% on different cohorts, and, after a logistic regression with both IPGS and age as inputs, it leads to an accuracy of 75%. The goal of this paper is to improve the previous results, using not only the most informative Boolean features with respect to the genetic bases of severity but also the information on host organs involved in the disease. In this study, we generalize the IPGS adding a statistical weight for each organ, through the transformation of Boolean features into “Boolean quantum features,” inspired by quantum mechanics. The organ coefficients were set via the application of the genetic algorithm PyGAD, and, after that, we defined two new integrated polygenic scores (IPGSph1 and IPGSph2). By applying a logistic regression with both IPGS, (IPGSph2 (or indifferently IPGSph1) and age as inputs, we reached an accuracy of 84%–86%, thus improving the results previously shown in Fallerini et al. (Human genetics, 2022, 141, 147–173) by a factor of 10%.

IntroductionIn classical Hodgkin lymphoma (cHL), the survival of neoplastic cells is mediated by the activation of NF-κB, JAK/STAT and PI3K/Akt signaling pathways. CK2 is a highly conserved serine/threonine kinase, consisting of two catalytic (α) and two regulatory (β) subunits, which is involved in several cellular processes and both subunits were found overexpressed in solid tumors and hematologic malignancies.Methods and resultsBiochemical analyses and in vitro assays showed an impaired expression of CK2 subunits in cHL, with CK2α being overexpressed and a decreased expression of CK2β compared to normal B lymphocytes. Mechanistically, CK2β was found to be ubiquitinated in all HL cell lines and consequently degraded by the proteasome pathway. Furthermore, at basal condition STAT3, NF-kB and AKT are phosphorylated in CK2-related targets, resulting in constitutive pathways activation. The inhibition of CK2 with CX-4945/silmitasertib triggered the de-phosphorylation of NF-κB-S529, STAT3-S727, AKT-S129 and -S473, leading to cHL cell lines apoptosis. Moreover, CX-4945/silmitasertib was able to decrease the expression of the immuno-checkpoint CD274/PD-L1 but not of CD30, and to synergize with monomethyl auristatin E (MMAE), the microtubule inhibitor of brentuximab vedotin.ConclusionsOur data point out a pivotal role of CK2 in the survival and the activation of key signaling pathways in cHL. The skewed expression between CK2α and CK2β has never been reported in other lymphomas and might be specific for cHL. The effects of CK2 inhibition on PD-L1 expression and the synergistic combination of CX-4945/silmitasertib with MMAE pinpoints CK2 as a high-impact target for the development of new therapies for cHL

Patients with chronic kidney disease (CKD) often experience mild cognitive impairment and other neurocognitive disorders. Studies have shown that erythropoietin (EPO) and its receptor have neuroprotective effects in cell and animal models of nervous system disorders. Recombinant human EPO (rHuEPO), commonly used to treat anemia in CKD patients, could be a neuroprotective agent. In this systematic review, we aimed to assess the published studies investigating the cognitive benefits of rHuEPO treatment in individuals with reduced kidney function. We comprehensively searched Pubmed, Cochrane Library, Scopus, and Web of Science databases from 1990 to 2023. After selection, 24 studies were analyzed, considering study design, sample size, participant characteristics, intervention, and main findings. The collective results of these studies in CKD patients indicated that rHuEPO enhances brain function, improves performance on neuropsychological tests, and positively affects electroencephalography measurements. These findings suggest that rHuEPO could be a promising neuroprotective agent for managing CKD-related cognitive impairment.

Abstract Background The localization of lung nodules is challenging during thoracoscopy. In this study, we evaluated the use of three‐dimensional (3D) lung reconstruction for use in the operating room to guide the identification of lung nodules during thoracoscopy. Methods This was a single‐center retrospective study. All consecutive patients undergoing thoracoscopic resection of lung nodules were included in the study. Patients were retrospectively divided into two groups based upon whether the thoracoscopic resection was performed with the assistance (3D group) or not (standard group) of 3D lung reconstruction. The operative time (minutes) to detect lung nodules was statistically compared between the two study groups in relation to the characteristics of lung nodules as size, localization, and distance from the visceral pleura. Results Our study population consisted of 170 patients: 85 in the 3D group and 85 in the standard group. No intergroup difference differences were found regarding the characteristics and histological diagnosis of lesions. The standard group compared to the 3D group was associated with a significantly longer operative time for the detection of lesions

Ring-tailed Lemur (Lemur catta) is the only surviving semi-terrestrial diurnal lemur in Madagascar. Despite being the most intensively studied of lemur taxa, only a few helminths have been described in this species. In this study we describe a persistent infection due to Trichostrongylus colubriformis in a captive population of L. catta hosted in a zoological park of northern Italy. In the context of a parasitological survey on zoo animals, we investigated parasites in a captive colony of ring-tailed lemurs within a zoological park. Parasitological analysis included necropsy of a deceased lemur in 2019, subsequent fecal sample collections in 2021–2022, followed by coprological examination and coprocolture. Morphological and molecular analyses were conducted on adult helminths, larvae and eggs, involving microscopy, scanning electron microscopy (SEM), and sequencing of the ITS rDNA region. Trichostrongylidae parasites were primarily found after necropsy in the intestine of the lemur. Morphological and molecular investigations on adults and eggs/larvae recovered from feces collected at different times from lemurs of the same captive population, allowed to properly identify the parasite as T. colubriformis. To the best of our knowledge this is the first description of T. colubriformis in L. catta. Although its presence in wild populations is not necessarily implied by our finding, this parasitosis represent a cause of concern in captive lemurs, considering the possibility of interspecies transmission and the zoonotic implications.

Abstract Background The management of respiratory distress syndrome (RDS) in premature newborns is based on different types of non-invasive respiratory support and on surfactant replacement therapy (SRT) to avoid mechanical ventilation as it may eventually result in lung damage. European guidelines currently recommend SRT only when the fraction of inspired oxygen (FiO2) exceeds 0.30. The literature describes that early SRT decreases the risk of bronchopulmonary dysplasia (BPD) and mortality. Lung ultrasound score (LUS) in preterm infants affected by RDS has proven to be able to predict the need for SRT and different single-center studies have shown that LUS may increase the proportion of infants that received early SRT. Therefore, the aim of this study is to determine if the use of LUS as a decision tool for SRT in preterm infants affected by RDS allows for the reduction of the incidence of BPD or death in the study group. Methods/design In this study, 668 spontaneously-breathing preterm infants, born at 25+0 to 29+6 weeks’ gestation, in nasal continuous positive airway pressure (nCPAP) will be randomized to receive SRT only when the FiO2 cut-off exceeds 0.3 (control group) or if the LUS score is higher than 8 or the FiO2 requirements exceed 0.3 (study group) (334 infants per arm). The primary outcome will be the difference in proportion of infants with BPD or death in the study group managed compared to the control group. Discussion Based on previous published studies, it seems that LUS may decrease the time to administer surfactant therapy. It is known that early surfactant administration decreases BPD and mortality. Therefore, there is rationale for hypothesizing a reduction in BPD or death in the group of patients in which the decision to administer exogenous surfactant is based on lung ultrasound scores. Trial registration ClinicalTrials.gov identifier NCT05198375 . Registered on 20 January 2022.

Conventional literature on sanctions tends to overfocus on measuring their political efficacy on targeted countries, accused of carrying out terrorist activities. More critically, other studies have focused on the ethical problems arising from the consequences that sanctions have on entire populations. Departing from these approaches, this article draws on Fidel Castro’s concept of the “Battle of Ideas” and argues that sanctions should be studied as a form of US-led imperialist warfare over the Global South. Taking the case of Libya, the article relies on archival sources (CIA [Central Intelligence Agency], US and Libyan government, and UN documents) as well as secondary literature, and argues that sanctions act as a form of economic warfare that supplants or complements the use of other forms of warfare, including military and non-military. In doing so, the article calls for a deeper and renewed engagement with the Third-Worldist Marxist theoretical lineage, when studying the question of financial subordination, dependency, war, and imperialism in the Arab world, and the Global South at large.

Abstract Following restrictions to control the spread of COVID-19, and subsequent vaccination campaigns, sentiments against such policies were quick to arise. While individual-level determinants that led to such attitudes have drawn much attention, there are also reasons to believe that the macro context in which these movements arose may contribute to their evolution. In this study, exploiting data on business activities which supported a major Italian anti-restriction and anti-vaccine movement, IoApro, using quantitative analysis that employs both a fractional response probit and logit model and a beta regression model, we investigate the relationship between socio-economic characteristics, institutional quality, and the flourishing of this movement. Our results suggest a U-shaped relationship between income and the proliferation of the movement, meaning that support for these movements increases the greater the degree of economic decline. Our results further indicate that the share of the population between 40 and 60 years old is positively related to support for such movements, as is institutional corruption.

The hemostatic system is characterized by a delicate balance between pro- and anticoagulant forces, and the smallest alteration can cause serious events such as hemorrhages or thrombosis. Although exercise has been shown to play a protective role in athletes, several factors may increase the risk of developing venous thromboembolism (VTE), including hemoconcentration induced by exertion, immobilization following sports injuries, frequent long-distance flights, dehydration, and the use of oral contraceptives in female athletes. Biomarkers such as D-dimer, Factor VIII, thrombin generation, inflammatory cytokines, and leukocyte count are involved in the diagnosis of deep vein thrombosis (DVT), although their interpretation is complex and may indicate the presence of other conditions such as infections, inflammation, and heart disease. Therefore, the identification of biomarkers with high sensitivity and specificity is needed for the screening and early diagnosis of thromboembolism. Recent evidence about the correlation between the intensity of physical activity and VTE is divergent, whereas the repeated gestures in sports such as baseball, hockey, volleyball, swimming, wrestling, or, on the other hand, soccer players, runners, and martial art training represent a risk factor predisposing to the onset of upper and lower DVT. Anticoagulant therapy is the gold standard, reducing the risk of serious complications such as pulmonary embolism. The aim of this review is to provide a general overview about the interplay between physical exercise and the risk of thromboembolism in athletes, focusing on the main causes of thrombosis in professional athletes and underlying the need to identify new markers and therapies that can represent a valid tool for safeguarding the athlete’s health.

Research into novel anti-Helicobacter pylori agents represents an important approach for the identification of new treatments for chronic gastritis and peptic ulcers, which are associated with a high risk of developing gastric carcinoma. In this respect, two series of azobenzenesulfonamides were designed, synthesized, and tested against a large panel of human and bacterial CAs to evaluate their inhibitory activity. In addition, computational studies of the novel primary benzenesulfonamides (4a–j) were performed to predict the putative binding mode to both HpCAs. Then, the antimicrobial activity versus H. pylori of the two series was also studied. The best-in-class compounds were found to be 4c and 4e among the primary azobenzenesulfonamides and 5c and 5f belonging to the secondary azobenzenesulfonamides series, showing themselves to exert a promising anti-H. pylori activity, with MIC values of 4–8 μg/mL and MBCs between 4 and 16 μg/mL. Moreover, the evaluation of their toxicity on a G. mellonella larva in vivo model indicated a safe profile for 4c,e and 5c,f. The collected results warrant considering these azobenzenesulfonamides as an interesting starting point for the development of a new class of anti-H. pylori agents.

The need to increase food safety and improve human health has led to a worldwide increase in interest in gamma-aminobutyric acid (GABA), produced by lactic acid bacteria (LABs). GABA, produced from glutamic acid in a reaction catalyzed by glutamate decarboxylase (GAD), is a four-carbon, non-protein amino acid that is increasingly used in the food industry to improve the safety/quality of foods. In addition to the possible positive effects of GABA, called a postbiotic, on neuroprotection, improving sleep quality, alleviating depression and relieving pain, the various health benefits of GABA-enriched foods such as antidiabetic, antihypertension, and anti-inflammatory effects are also being investigated. For all these reasons, it is not surprising that efforts to identify LAB strains with a high GABA productivity and to increase GABA production from LABs through genetic engineering to increase GABA yield are accelerating. However, GABA’s contributions to food safety/quality and human health have not yet been fully discussed in the literature. Therefore, this current review highlights the synthesis and food applications of GABA produced from LABs, discusses its health benefits such as, for example, alleviating drug withdrawal syndromes and regulating obesity and overeating. Still, other potential food and drug interactions (among others) remain unanswered questions to be elucidated in the future. Hence, this review paves the way toward further studies.

The purple carrot cultivar ‘Purple Sun’ (Daucus carota L.) is characterized by a relevant content of phenolic compounds and anthocyanins, which may play an important role in reducing the risk of chronic diseases and in the treatment of metabolic syndrome. In the present study, the genetic diversity, phytochemical composition, and bioactivities of this outstanding variety were studied for the first time. Genetic analysis by molecular markers estimated the level of genetic purity of this carrot cultivar, whose purple-pigmented roots were used for obtaining the purple carrot ethanol extract (PCE). With the aim to identify specialized metabolites potentially responsible for the bioactivities, the analysis of the metabolite profile of PCE by LC-ESI/LTQ Orbitrap/MS/MS was carried out. LC-ESI/HRMS analysis allowed the assignment of twenty-eight compounds, putatively identified as isocitric acid (1), phenolic acid derivatives (2 and 6), hydroxycinnamic acid derivatives (9, 10, 12–14, 16, 17, 19, 22, and 23), anthocyanins (3–5, 7, 8, 11, and 18), flavanonols (15 and 21), flavonols (20 and 24), oxylipins (25, 26, and 28), and the sesquiterpene 11-acetyloxytorilolone (27); compound 26, corresponding to the primary metabolite trihydroxyoctanoic acid (TriHOME), was the most abundant compound in the LC-ESI/HRMS analysis of the PCE, and hydroxycinnamic acid derivatives followed by anthocyanins were the two most represented groups. The antioxidant activity of PCE, expressed in terms of reactive oxygen species (ROS) level and antioxidant enzymes activity, and its pro-metabolic effect were evaluated. Moreover, the antibacterial activity on Gram (−) and (+) bacterial strains was investigated. An increase in the activity of antioxidant enzymes (SOD, CAT, and GPx), reaching a maximum at 0.5 mg/mL of PCE with a plateau at higher PCE concentrations (1.25, 2.5, and 5.0 mg/mL), was observed. PCE induced an initial decrease in ROS levels at 0.1 and 0.25 mg/mL concentrations, reaching the ROS levels of control at 0.5 mg/mL of PCE with a plateau at higher PCE concentrations (1.25, 2.5, and 5.0 mg/mL). Moreover, significant antioxidant and pro-metabolic effects of PCE on myoblasts were shown by a reduction in ROS content and an increase in ATP production linked to the promotion of mitochondrial respiration. Finally, the bacteriostatic activity of PCE was shown on the different bacterial strains tested, while the bactericidal action of PCE was exclusively observed against the Gram (+) Staphylococcus aureus. The bioactivities of PCE were also investigated from cellular and molecular points of view in colon and hematological cancer cells. The results showed that PCE induces proliferative arrest and modulates the expression of important cell-cycle regulators. For all these health-promoting effects, also supported by initial computational predictions, ‘Purple Sun’ is a promising functional food and an optimal candidate for pharmaceutical and/or nutraceutical preparations.

Cardiovascular diseases (CVDs) remain a leading global cause of morbidity and mortality. These diseases have a multifaceted nature being influenced by a multitude of biochemical, genetic, environmental, and behavioral factors. Epigenetic modifications have a crucial role in the onset and progression of CVD. Epigenetics, which regulates gene activity without altering the DNA’s primary structure, can modulate cardiovascular homeostasis through DNA methylation, histone modification, and non-coding RNA regulation. The effects of environmental stimuli on CVD are mediated by epigenetic changes, which can be reversible and, hence, are susceptible to pharmacological interventions. This represents an opportunity to prevent diseases by targeting harmful epigenetic modifications. Factors such as high-fat diets or nutrient deficiencies can influence epigenetic enzymes, affecting fetal growth, metabolism, oxidative stress, inflammation, and atherosclerosis. Recent studies have shown that plant-derived bioactive compounds can modulate epigenetic regulators and inflammatory responses, contributing to the cardioprotective effects of diets. Understanding these nutriepigenetic effects and their reversibility is crucial for developing effective interventions to combat CVD. This review delves into the general mechanisms of epigenetics, its regulatory roles in CVD, and the potential of epigenetics as a CVD therapeutic strategy. It also examines the role of epigenetic natural compounds (ENCs) in CVD and their potential as intervention tools for prevention and therapy.

The preservation of cultural heritage, particularly historical stone structures, represents a very challenging matter due to several environmental and anthropogenic factors. Vicenza stone, a calcareous rock known for its historical significance and widespread use in architectural masterpieces, requires significant attention for conservation. In fact, as the demand for sustainable and effective preservation methods intensifies, the exploration of innovative consolidation strategies becomes essential. To this end, inorganic consolidants, based on alkaline silicate formulations and nano-silica, were explored for their promising performance in enhancing the surface properties and chemical stability of Vicenza stone. In particular, the durability of treated and untreated Vicenza stone samples was evaluated by means of accelerated weathering tests such as freeze–thaw cycles, salt crystallization and simulation of acid rain. The experimental results revealed that Vicenza stone is very resistant to the effects of freeze–thaw cycles and acid rain; both the accelerated weathering tests did not show significant differences between treated and untreated VS samples. A different behavior was detected for the test for resistance to salt crystallization, whose findings led us to deduce that, for this kind of degradation, it is possible to observe a more beneficial effect of the consolidation treatments on the stone durability.

Purpose: The aim of this article is to analyze the incidence of undiagnosed obstructive sleep apnea (OSA) in patients affected by dento-skeletal malformation. We also evaluated the patterns most affected by the condition and calculated the post surgical changes. Methods: We conducted a retrospective cohort study on 71 patients including 35 men and 36 women. The patients studied were affected by dento-skeletal class II and III malformations and underwent bimaxillary orthognathic surgery in all cases. Patients were evaluated with polysomnography before surgery and at least 6 months after surgery to assess any improvement or worsening of the apnea hypopnea index (AHI) index. Regarding AHI evaluation criteria, an AHI > 5 was considered indicative of OSA, 4 < AHI < 5 was considered borderline and AHI < 4 was considered indicative of non-OSA. We also considered demographic variables like age at the time of intervention and gender, and anatomical variables like the pattern of the dento-skeletal deformity and the presence or absence of maxillary hypoplasia. Qualitative variables were described as absolute and relative frequencies, while quantitative variables were summarized as mean and standard deviation. To quantitatively express the relationship between two variables, the correlation coefficient was calculated. The covariance array was used to evaluate multiple correlations. Results: Our study shows that there is a significant percentage (33%) of patients who undergo orthognathic surgery with an AHI > 5 and also a percentage of patients (11%) who can be considered to be “borderline.” It emerges that the pattern most at risk is the one characterized by retruded maxilla and patients with dento-skeletal class II. Considering the post surgical period, the statistical analysis shows that after surgery, only 8% of malformed patients present an AHI > 5, compared to the 20.5% described in the Italian population. Conclusions: In patients who receive orthognathic surgery, the presence of obstructive sleep apnea is significantly higher than in the general population. When planning the surgical correction of a dento-skeletal malformation, the surgeon must aim not only for the esthetics results, but also for proper stomatognathic and respiratory function; this cannot be achieved without taking polysomnography information into account.

Background: The mismatch between tricuspid valve (TV) leaflet length and annulus dilation, assessed with the septal–lateral leaflet-to-annulus index (SL-LAI), predicts residual tricuspid regurgitation (TR) following tricuspid transcatheter edge-to-edge-repair (T-TEER). When posterior leaflet grasping is required, the anterior–posterior leaflet-to-annulus index (AP-LAI) may offer additional information. Methods: This single-center retrospective cohort study included all patients referred for T-TEER with severe and symptomatic TR with high surgical risk from April 2021 to March 2024. Patients were categorized into ‘optimal result’ (Results: Of the 25 patients, 12 had suboptimal post-procedural results, while 13 showed optimal outcomes. The optimal result group showed a higher prevalence of type IIIA-IIIB TV morphology (85% vs. 45%, p < 0.05), a wider SL annulus diameter (42.5 ± 5 vs. 37 ± 5 mm, p < 0.05), and a longer posterior leaflet length (28 ± 4 vs. 22 ± 5 mm, p < 0.01). The SL-LAI was lower in the optimal group (1 ± 0.2 vs. 1.2 ± 0.32, p < 0.05), while the AP-LAI was higher (0.7 ± 0.1 vs. 0.5 ± 0.2, p < 0.05). ROC curve analysis showed that the AUC for the AP-LAI was 0.769 (95% CI 0.51–0.93, p < 0.05) and Youden test identified the best cut-off value p = 0.01). Conclusions: The AP-LAI and SL-LAI can help in predicting post T-TEER results, ameliorating patients’ outcomes and avoiding futile procedures.

Conversaciones pedagógicas y políticas educativas entre (contra)visualidades y prácticas. Entrevista a Inés Dussel

En este artículo se propone analizar la visualidad construida en rechazo a la potencial explotación petrolera en la costa Atlántica (provincia de Buenos Aires, Argentina). Estas acciones críticas forman parte del conjunto de demandas socioambientales que en la actualidad oponen al modelo de desarrollo basado en el extractivismo. Por un lado, se estudiarán algunas imágenes producidas en el marco de las marchas denominadas Atlanticazo. Por otro, se analizará la creación de una estampita, llamada San Lobito de Mar, imagen acompañada de una oración de protección contra la acción humana dañina. Se concluye que las imágenes estudiadas tienen un potencial contravisual: posicionan a los seres vivientes y su entorno en un rol activo, desde la exigencia del derecho a vivir y existir y no como mero recursos a ser explotados por el humano. La metodología propuesta, es cualitativa, basada en entrevistas a activistas, análisis iconográfico y recolección de información en redes sociales y medios digitales. Asimismo, el marco teórico recupera herramientas provistas por los Estudios visuales, la Teoría política y la Ecología política.

Objective: To determine the feasibility of a self-directed training protocol to promote actual arm use in everyday life. The secondary aim was to explore the initial efficacy on upper extremity (UE) outcome measures. Design: Feasibility study using multiple methods. Setting: Home and outpatient research lab. Participants: Fifteen adults (6 women, 9 men, mean age=53.08 years) with chronic stroke living in the community. There was wide range of UE functional levels, ranging from dependent stabilizer (limited function) to functional assist (high function). Intervention: Use My Arm-Remote protocol. Phase 1 consisted of clinician training on motivational interviewing (MI). Phase 2 consisted of MI sessions with participants to determine participant generated goals, training activities, and training schedules. Phase 3 consisted of UE task-oriented training (60 minutes/day, 5 days/week, for 4 weeks). Participants received daily surveys through an app to monitor arm training behavior and weekly virtual check-ins with clinicians to problem-solve challenges and adjust treatment plans. Outcome Measures: Primary outcome measures were feasibility domains after intervention, measured by quantitative study data and qualitative semi-structured interviews. Secondary outcomes included the Canadian Occupational Performance Measure (COPM), Motor Activity Log (MAL), Fugl-Meyer Assessment (FMA), and accelerometry-based duration of use metric measured at baseline, discharge, and 4-week follow-up. Results: The UMA-R was feasible in the following domains: recruitment rate, retention rate, intervention acceptance, intervention delivery, adherence frequency, and safety. Adherence to duration of daily practice did not meet our criteria. Improvements in UE outcomes were achieved at discharge and maintained at follow-up as measured by COPM-Performance subscale (F[1.42, 19.83]=17.72, P

Cluster synchronization is a general phenomenon in a network of non-locally coupled oscillators. Here, we show that cluster synchronization occurs in semiconductor lasers, where the beat notes between the pairs of adjacent longitudinal modes of the laser cavity constitute a collection of coupled phase oscillators. Non-local coupling arises from the standing-wave nature of the cavity with finite mirror reflectivities, which we can actively control. Varying the coupling, we can bring the laser into a state of cluster synchronization where the two beat note families oscillate at two distinct collective frequencies. Using a coherent beat note detection technique, we show that the beat notes within the two families are synchronized in the opposite configurations—in-phase and antiphase.