Università degli Studi del Molise

Background Adult mosquitoes of the genus Anopheles are important vectors of Plasmodium parasites, causative agents of malaria. The aim of this review was to synthesize the overall and species-specific proportion of Anopheles species infected with sporozoites and their geographical distribution in the last 2 decades (2001–2021). Methods A comprehensive search was conducted using databases (PubMed, Google Scholar, Science Direct, Scopus, African Journals OnLine) and manual Google search between January 1 and February 15, 2022. Original articles describing work conducted in Ethiopia, published in English and reporting infection status, were included in the review. All the required data were extracted using a standardized data extraction form, imported to SPSS-24, and analyzed accordingly. The quality of each original study was assessed using a quality assessment tool adapted from the Joanna Briggs Institute critical appraisal checklist. This study was registered on PROSPERO (International Prospective Register of Systematic Reviews; registration no. CRD42022299078). Results A search for published articles produced a total of 3086 articles, of which 34 met the inclusion criteria. Data on mosquito surveillance revealed that a total of 129,410 anophelines comprising 25 species were captured, of which 48,365 comprising 21 species were tested for sporozoites. Anopheles arabiensis was the dominant species followed by An. pharoensis and An. coustani complex. The overall proportion infected with sporozoites over 21 years was 0.87%. Individual proportions included Anopheles arabiensis (1.09), An. pharoensis (0.79), An. coustani complex (0.13), An. funestus (2.71), An. demeilloni (0.31), An. stephensi (0.70), and An. cinereus (0.73). Plasmodium falciparum sporozoites accounted 79.2% of Plasmodium species. Mixed infection of Plasmodium vivax and P. falciparum was only reported from one An. arabiensis sample. Conclusions Anopheles arebiensis was the dominant malaria vector over the years, with the highest sporozoite infection proportion of 2.85% and an average of 0.90% over the years. Other species contributing to malaria transmission in the area were An. pharoensis, An. coustani complex, An. funestus, An. stephensi, and An. coustani. The emergence of new vector species, in particular An. stephensi, is particularly concerning and should be investigated further. Graphical Abstract

Objectives Shared decision-making (SDM) is advocated to improve patient outcomes in Psoriatic arthritis (PsA). We analysed current prescribing practices and the extent of SDM in PsA across Europe. Methods The ASSIST study was a cross-sectional observational study of PsA patients aged ≥18 years attending face-to-face appointments between July 2021-March 2022. Patient demographics, current treatment and treatment decisions were recorded. SDM was measured by the clinician’s effort to collaborate (CollaboRATE questionnaire) and patient communication confidence (PEPPI-5 tool). Results 503 patients were included from 24 centres across the UK, France, Germany, Italy and Spain. Physician- and patient-reported measures of disease activity were highest in the UK. Conventional synthetic DMARDs constituted a higher percentage of current PsA treatment in UK than continental Europe (66.4% vs 44.9%), which differed from biologic DMARDs (36.4% vs 64.4%). Implementing treatment escalation was most common in the UK. CollaboRATE and PEPPI-5 scores were high across centres. Of 31 patients with low CollaboRATE scores (<4.5), no patients with low PsAID-12 scores (<5) had treatment escalation. However, of 465 patients with CollaboRATE scores ≥4.5, 59 patients with low PsAID-12 scores received treatment escalation. Conclusions Higher rates of treatment escalation seen in the UK may be explained by higher disease activity and a younger cohort. High levels of collaboration in face-to-face PsA consultations suggests effective implementation of the SDM approach. Our data indicate that, in patients with mild disease activity, only those with higher perceived collaboration underwent treatment escalation. Prospective studies should examine the impact of SDM on PsA patient outcomes. Trial registration clinicaltrials.gov, NCT05171270

Background and Objectives: Despite advancements in the diagnosis and treatment of testicular germ cell tumours (TGTCs), challenges persist in identifying reliable biomarkers for early detection and precise disease management. This narrative review addresses the role of microRNAs (miRNAs) as potential diagnostic tools and therapeutic targets in the treatment of TGCTs. Materials and Methods: Three databases (PubMed®, Web of Science™, and Scopus®) were queried for studies investigating the utility of miRNA as diagnostic tools, assessing their prognostic significance, and evaluating their potential to guide TGCT treatment. Different combinations of the following keywords were used, according to a free-text protocol: “miRNA”, “non-coding RNA”, “small RNA”, “Testicular Cancer”, “seminomatous testicular germ cell”, “non-seminomatous testicular germ cell”. Results: The potential of miRNAs as possible biomarkers for a non-invasive diagnosis of TGCT is appealing. Their integration into the diagnostic pathway for TGCT patients holds the potential to enhance the discriminative power of conventional serum tumour markers (STMs) and could expedite early diagnosis, given that miRNA overexpression was observed in 50% of GCNIS cases. Among miRNAs, miR-371a-3p stands out with the most promising evidence, suggesting its relevance in the primary diagnosis of TGCT, particularly when conventional STMs offer limited value. Indeed, it demonstrated high specificity (90–99%) and sensitivity (84–89%), with good positive predictive value (97.2%) and negative predictive value (82.7%). Furthermore, a direct relationship between miRNA concentration, disease burden, and treatment response exists, regardless of disease stages. The initial evidence of miRNA decrease in response to surgical treatment and systemic chemotherapy has been further supported by more recent results suggesting the potential utility of this tool not only in evaluating treatment response but also in monitoring residual disease and predicting disease relapse. Conclusions: MiRNAs could represent a reliable tool for accurate diagnosis and disease monitoring in the treatment of TGCT, providing more precise tools for early detection and treatment stratification. Nevertheless, well-designed clinical trials and comprehensive long-term data are needed to ensure their translation into effective clinical tools.

Objective Variants in several potassium channel genes, including KCNA1 and KCNA2 , cause Developmental and Epileptic Encephalopathies (DEEs). We investigated whether variants in KCNA3 , another mammalian homologue of the Drosophila shaker family and encoding for Kv1.3 subunits, can cause DEE. Methods Genetic analysis of study individuals was performed by routine exome or genome sequencing, usually of parent‐offspring trios. Phenotyping was performed via a standard clinical questionnaire. Currents from wild‐type and/or mutant Kv1.3 subunits were investigated by whole‐cell patch‐clamp upon their heterologous expression. Results Fourteen individuals, each carrying a de novo heterozygous missense variant in KCNA3, were identified. Most (12/14; 86%) had DEE with marked speech delay with or without motor delay, intellectual disability, epilepsy, and autism spectrum disorder. Functional analysis of Kv1.3 channels carrying each variant revealed heterogeneous functional changes, ranging from “pure” loss‐of‐function (LoF) effects due to faster inactivation kinetics, depolarized voltage‐dependence of activation, slower activation kinetics, increased current inactivation, reduced or absent currents with or without dominant‐negative effects, to “mixed” loss‐ and gain‐of‐function (GoF) effects. Compared to controls, Kv1.3 currents in lymphoblasts from one of the proband displayed functional changes similar to those observed upon heterologous expression of channels carrying the same variant. The antidepressant drug fluoxetine inhibited with similar potency the currents from wild‐type and one of the Kv1.3 GoF variant. Interpretation We describe a novel association of de novo missense variants in KCNA3 with a human DEE, and provide evidence that fluoxetine might represent a potential targeted treatment for individuals carrying variants with significant GoF effects. This article is protected by copyright. All rights reserved.

Introduction Pediatric obesity has steadily increased in recent decades. Large-scale genome-wide association studies (GWAS) conducted primarily in Eurocentric adult populations have identified approximately 100 loci that predispose to obesity and type II diabetes. GWAS in children and individuals of non-European descent, both disproportionately affected by obesity, are fewer. Rare syndromic and monogenic obesities account for only a small portion of childhood obesity, so understanding the role of other genetic variants and their combinations in heritable obesities is key to developing targeted and personalized therapies. Tight and responsive regulation of the cAMP-dependent protein kinase (PKA) signaling pathway is crucial to maintaining healthy energy metabolism, and mutations in PKA-linked genes represent the most common cause of monogenic obesity. Methods For this study, we performed targeted exome sequencing of 53 PKA signaling-related genes to identify variants in genomic DNA from a large, ethnically diverse cohort of obese or metabolically challenged youth. Results We confirmed 49 high-frequency variants, including a novel variant in the PDE11A gene (c.152C>T). Several other variants were associated with metabolic characteristics within ethnic groups. Discussion We conclude that a PKA pathway-specific variant search led to the identification of several new genetic associations with obesity in an ethnically diverse population.

The aim of the present work was to evaluate and compare in vitro the antioxidant activity of raw, cooked and cooked–digested pork, beef and chicken burgers. The cooking process influenced the antioxidant capacity of the meat by decreasing the values of ABTS, FRAP and the content of free thiols. Conversely, a positive effect was observed after in vitro gastrointestinal digestion which increased the biological activity of the meat, characterised by greater antioxidant activity. The type of meat influenced the chemical composition and biological capacity of the burgers. In fact, both before and after the cooking process, beef burgers showed higher thiol content and, consequently, a higher oxidative stability of proteins than chicken and pork burgers. In vitro gastrointestinal digestion also improved the nutraceutical quality of beef burgers, which showed higher ABTS values and thiol content than pork burgers, which showed higher FRAP values. This work aims to support the potential of meat constituents as a natural antioxidant component that is essential to counteract the oxidative stress responsible for imbalances in the human organism and several cardiovascular diseases.

Inferior vena cava leiomyosarcoma is a rare malignant mesenchymal tumor that originates from the smooth muscle cells of the venous media and is more frequent in females in the V-VI decade of life. Due to scarce and specific symptoms, diagnosis is not simple, and often metastases to the liver, lungs, and/or lymph nodes are already present. A 44-year-old male patient arrives at our institution presenting diffuse abdominal pain and a sense of weight associated with lumbar pain. He showed nothing relevant except for a moderate consumption of alcohol. Ultrasound examination of the abdomen revealed liver enlargement with hyperechoic nodularity and clear margins. Furthermore, the presence of a voluminous solid nodular formation was found, with an inhomogeneous echostructure and moderate vascularization on Doppler. Inferior vena cava leiomyosarcoma is a rare malignancy. The diagnosis is usually established after surgery, however, recurrences are common and the role of chemoradiation therapy remains to be defined. The only potential treatment is surgical resection with possible vessel reconstruction and en bloc removal of adjacent structures with 5 and 10-year survival rates of 49% and 29%, respectively.

This study aims to explore whether members of Generation Z have sensitivity and awareness about environmental issues related to seafood production and consumption, their beliefs on how to make more sustainable the future provisioning of seafood, their consumption frequency, and, finally, whether different profiles and groups of people could be detected. A survey was implemented with 778 Italian students attending secondary schools. Descriptive statistics, testing, and cluster analyses were applied. Results provide the sustainability profile of five groups, of which three are aligned with SDGs 12 and 14, but the other groups, comprising almost half of the sample, are insensitive, unaware, or irresolute about the sustainability of seafood production and consumption. Overall, people’s environmental consciousness does not appear to be strongly related to the frequency of consumption of sustainable seafood species. Regarding the solutions for improving the sustainability of future seafood production, young respondents underlined the catching and raising of novel, discarded, not exploited, or marginally exploited seafood species. People declared a high knowledge of the nutritional and safety implications of seafood. This study is one of the few that explore issues specifically related to the profiles of Generation Z and young people’s approach toward sustainable seafood production and consumption.

Assessing forest biodiversity, naturalness and old-growth status (B-N-OG) is crucial for supporting sustainable forest planning, yet comprehensive monitoring networks specifically designed for such purposes are lacking in many countries. National Forest Inventories (NFIs) are the official source of statistics on status and trends of forests. While initially designed for wood production assessment, NFI data may be pivotal for ecological forest monitoring, thanks to their robust sampling protocols—enabling statistical inference—and regular field campaigns that ensure continuous information updates. As a consequence, in this study we explore the potential of NFIs for estimating B-N-OG indexes, aiming to establish compatible, scientifically relevant, and cost-effective indicators using existing NFI data at a European level. Based on data from the 2005 Italian NFI collected from 6563 plots, 18 indicators were selected following previous experiences and then used to estimate B-N-OG aggregated indexes. Relationships between the 18 indicators and the three indexes were investigated, along with comparisons of their relationships relative to forest type categories, management types and protected versus non-protected areas. Results confirm that NFI data offer valuable insights into specific B-N-OG indexes, especially concerning forest structure and deadwood. Moreover, the indexes contribute to developing meaningful relationships across geographic regions, forest categories and types of management. However, limitations in NFI field protocols are evident, as they are not explicitly designed for certain indicators. The study suggests the potential for NFIs to evolve into accessible, harmonized European reference networks for B-N-OG assessment for better supporting sustainable forest management, planning and conservation decisions related to forest ecosystems.

Introduction: In Paralympic powerlifting competitions, movement execution symmetry is a technical requirement influenced by individual athlete characteristics and motor strategies. Identifying the elements associated with individual motor strategies can offer valuable insight for improving sport performance. Therefore, this case series study aimed to explore muscle activation symmetry and its intra- and inter-individual variability to determine the muscles mostly related to individual motor strategies in elite Paralympic powerlifters. Methods: Bilateral electromyographic activation of the anterior deltoid (AD), pectoralis major (PM), latissimus dorsi (LD), triceps (TRI) and external oblique (EO) muscles were analysed in five elite Paralympic powerlifters while performing four sets of one-repetition maximum of Paralympic bench press. Muscle activation symmetry indexes (SI) were obtained and transformed to consider individual-independent evaluation. The coefficient of variation (CV), variance ratio (VR), and mean deviation (MD) were computed to assess inter- and intra-individual variability in electromyographic waveforms and SI. Results: Both transformed and non-transformed SI indicated overall symmetric activation in DA, PM, TRI, and LD. Transformed SI revealed asymmetrical muscle activation of EO when grouping data (mean bilateral difference: 10%). Athletes exhibited low intra-individual SI variability in all analysed muscles (CV < 10%) and low inter-individual variability in DA, PM, LD, and TRI (CV < 10%; VR: 4%–11%; MD: 29%–43%). In contrast, higher inter-individual variability was observed in EO (CV: 23%; VR: 23%; MD: 72%–81%). Conclusion: The highest variability and asymmetry in abdominal muscle activation among athletes emphasize the importance of personalized training approaches for targeting these muscles due to their role in individualizing motor strategies.

Many pathological conditions, including obesity, diabetes, hypertension, heart disease, and cancer, are associated with abnormal metabolic states. The progressive loss of metabolic control is commonly characterized by insulin resistance, atherogenic dyslipidemia, inflammation, central obesity, and hypertension, a cluster of metabolic dysregulations usually referred to as the “metabolic syndrome”. Recently, nutraceuticals have gained attention for the generalized perception that natural substances may be synonymous with health and balance, thus becoming favorable candidates for the adjuvant treatment of metabolic dysregulations. Among nutraceutical proteins, lactoferrin (Lf), an iron-binding glycoprotein of the innate immune system, has been widely recognized for its multifaceted activities and high tolerance. As this review shows, Lf can exert a dual role in human metabolism, either boosting or resetting it under physiological and pathological conditions, respectively. Lf consumption is safe and is associated with several benefits for human health, including the promotion of oral and gastrointestinal homeostasis, control of glucose and lipid metabolism, reduction of systemic inflammation, and regulation of iron absorption and balance. Overall, Lf can be recommended as a promising natural, completely non-toxic adjuvant for application as a long-term prophylaxis in the therapy for metabolic disorders, such as insulin resistance/type II diabetes and the metabolic syndrome.

The overuse and misuse of antibiotics have led to the emergence and spread of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) bacteria strains, usually associated with poorer patient outcomes and higher costs. In order to preserve the usefulness of these life-saving drugs, it is crucial to use them appropriately, as also recommended by the WHO. Moreover, innovative, safe, and more effective approaches are being investigated, aiming to revise drug treatments to improve their pharmacokinetics and distribution and to reduce the onset of drug resistance. Globally, to reduce the burden of antimicrobial resistance (AMR), guidelines and indications have been developed over time, aimed at narrowing the use and diminishing the environmental spread of these life-saving molecules by optimizing prescriptions, dosage, and times of use, as well as investing resources into obtaining innovative formulations with better pharmacokinetics, pharmacodynamics, and therapeutic results. This has led to the development of new nano-formulations as drug delivery vehicles, characterized by unique structural properties, biocompatible natures, and targeted activities such as state-of-the-art phospholipid particles generally grouped as liposomes, virosomes, and functionalized exosomes, which represent an attractive and innovative delivery approach. Liposomes and virosomes are chemically synthesized carriers that utilize phospholipids whose nature is predetermined based on their use, with a long track record as drug delivery systems. Exosomes are vesicles naturally released by cells, which utilize the lipids present in their cellular membranes only, and therefore, are highly biocompatible, with investigations as a delivery system having a more recent origin. This review will summarize the state of the art on microvesicle research, liposomes, virosomes, and exosomes, as useful and effective tools to tackle the threat of antibiotic resistance.

The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) is well recognized as a critical regulator of redox, metabolic, and protein homeostasis, as well as the regulation of inflammation. An age-associated decline in NRF2 activity may allow oxidative stress to remain unmitigated and affect key features associated with the aging phenotype, including telomere shortening. Telomeres, the protective caps of eukaryotic chromosomes, are highly susceptible to oxidative DNA damage, which can accelerate telomere shortening and, consequently, lead to premature senescence and genomic instability. In this review, we explore how the dysregulation of NRF2, coupled with an increase in oxidative stress, might be a major determinant of telomere shortening and age-related diseases. We discuss the relevance of the connection between NRF2 deficiency in aging and telomere attrition, emphasizing the importance of studying this functional link to enhance our understanding of aging pathologies. Finally, we present a number of compounds that possess the ability to restore NRF2 function, maintain a proper redox balance, and preserve telomere length during aging.

Lactoferrin (Lf), a naturally occurring glycoprotein involved in innate immunity, was first discovered in bovine milk [...]