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We aimed to evaluate whether progression-directed radiation therapy (PDRT) can prolong the initiation of a subsequent systemic therapy regimen in a cohort of patients with oligoprogressive NSCLC. A retrospective analysis was conducted on NSCLC patients who underwent PDRT for extracranial oligoprogressive NSCLC, defined as limited (up to five) progressing lesions following initial complete, partial, or stable response to systemic therapy according to REC1ST 1.1 and/or PERCIST 1.0 criteria. Cox proportional hazard regressions were performed to identify factors influencing time to next treatment (TTNT), which was considered the primary endpoint. Forty patients were analyzed. First, second, and ≥3 lines of systemic therapy were administered in 22 (58.2%), 14 (27.2%), and 4 (14.6%) cases, respectively. The median total dose was 36 Gy (range: 12–60) in five fractions (1–10), with a median biological effective dose for tumor control (BED10) of 52 Gy (26.4–151.2). After a median follow-up of 11 months (2–50), PDRT delayed further systemic therapy in 32 (80.0%) treatments. Median TTNT was not reached at 8 months (1–47) with a one-year Kaplan–Meier estimate of 81.4% (95% CI: 75.0% to 87.8%). No >grade 3 adverse event was observed. On multivariate analysis, patients with ≥3 lines of systemic therapy and/or with larger CTV volumes did not benefit from PDRT. Despite the use of sub-ablative doses, our findings show that PDRT represents an effective, safe, and viable option for oligoprogressive NSCLC. Patients irradiated early during their systemic treatment course, with a low volume of disease and nonmetastatic oligoprogression, could derive substantial benefits from PDRT. [ABSTRACT FROM AUTHOR]

Heterozygous mutations or genetic variants in the GBA1 gene, which encodes for the β-glucocerebrosidase (GCase), a lysosomal hydrolase enzyme, may increase the risk of Parkinson's disease (PD) onset. The heterozygous E326K form is one of the most common genetic risk factors for PD worldwide, but, to date, the underlying molecular mechanisms remain unclear. Here, we investigate the effect of the E326K on the structure, stability, dimerization process, and interaction mode with some proteins of the interactome of GCase using multiple molecular dynamics (MD) simulations at pH 5.5 and pH 7.0 to mimic the lysosomal and endoplasmic reticulum environments, respectively. The analysis of the MD trajectories highlights that the E326K mutation did not significantly alter the structural conformation of the catalytic dyad but significantly makes the structure of the dimeric complexes unstable, especially at lysosomal pH, potentially impacting the organization of the quaternary structure. Furthermore, the E326K mutation significantly impacts protein interactions by altering the binding mode with the activator Saposin C (SapC), reducing the binding affinity with the inhibitor α-Synuclein (α-Syn), and increasing the affinity for the Lysosomal integral membrane protein-2 (LIMP-2) transporter. [ABSTRACT FROM AUTHOR]

The purpose of this clinical epidemiological investigation was to examine the oral health conditions of homeless people in the city of Rome, Italy. A total of 157 homeless subjects were subjected to a first dental visit, during which anamnestic information was recorded in a digital medical record. A diagnosis of dental disorders was performed by assessing oral hygiene conditions, periodontal health, the presence of caries and/or root residues, and the presence of partial and/or total edentulousness. Caries and missing teeth were evaluated by the DMFT index. The first major criticality was represented by poor or absent oral hygiene. The examined sample showed a major percentage of high DMFT (63.0%); the most common clinical condition was the presence of numerous root residues. Regarding periodontal health, 73.2% of patients had gingivitis, 21.6% periodontitis, while 11 patients had periodontal pathologies with tooth mobility (7%). Finally, 8.9% of patients had one or two missing elements, 22.9% had partial edentulousness, and 8.9% of the sample had total edentulism. This analysis provides an important basis for strengthening health promotion and the importance of accessible and effective care for this population. It will therefore be necessary to continue to adopt a patient-centered approach geared towards addressing the demands that this population faces in maintaining their oral health. [ABSTRACT FROM AUTHOR]

Background/Objectives: Although rare in the Western world, dog bites may be lethal or lead to physically severe outcomes. However, little attention is given to their psychological consequences. We aimed to review their psychological consequences in children 1–14 years of age, focusing on the prevalence and nature of psychological disorders, evaluating the impact on future mental health of children and their families, and assessing the effectiveness of preventive interventions and measures. Methods: On 23 May 2024, we investigated the PubMed, CINAHL, and PsycINFO/PsycARTICLES databases using ("dog bite" OR animal-induced OR animal-caused) AND (psychol* OR mental OR psychiatr* OR anxiety OR anxious OR depress* OR obsess* OR trauma* OR psychosis OR psychotic OR schizophren* OR schizoaffect*) filtered for ages 0–18 years. This resulted in 311 records, of which 50 were eligible. These included original research, case reports, patient surveys, and reviews/meta-analyses. Results: Findings indicate that younger children are particularly vulnerable, often suffering head/neck bites, leading to severe injuries and psychological distress, with post-traumatic stress disorder (PTSD) being a common outcome. Symptoms such as nightmares, flashbacks, anxiety, and social withdrawal were frequently reported. Positive parental support and timely psychological interventions were found to mitigate these effects. Conclusions: Interdisciplinary approaches integrating education, cognitive restructuring, and behaviour modification are needed to effectively prevent and address the psychological impacts of dog bites. Summarising, dog bites in children result in substantial psychological sequelae, necessitating robust prevention and intervention strategies to improve their quality of life and reduce the risk of chronic mental conditions. [ABSTRACT FROM AUTHOR]

Simple Summary: Although some of the novel systemic treatments, especially the group of tyrosine kinase inhibitors, have shown a durable central nervous system response, ionizing radiation remains the mainstay in the management of brain metastases (BM). Recent technological advancements have enabled the replacement of whole-brain radiotherapy with localized stereotactic radiotherapy (SRT) for treating up to 10 BM, either as a primary or combined treatment, reducing neurotoxicity and improving local control (LC). The delivered target dose and patient selection play a crucial role in enhancing treatment efficacy. However, there is still limited evidence supporting which factors most affect LC and which patients derive the greatest benefit from SRT. This retrospective single-institutional study evaluated treatment outcomes in a heterogeneous patient population treated with Linac-based SRT, with the aim of identifying potential dosimetric and clinical prognostic factors to better inform the decision-making process. Background/Objectives: To report on predictive factors in Linac-based SRT for single and multiple BM. Methods: Consecutive patients receiving either one or three fractions of single-isocenter coplanar VMAT SRT were retrospectively included. The GTV-PTV margin was 1–2 mm. The delivered target dose was estimated by recalculating the original plans on roto-translated CT according to errors recorded by post-treatment CBCT. The Kaplan–Meier method estimated local progression-free survival (LPFS), intracranial progression-free survival (IPFS), and overall survival (OS). Log-rank and Wilcoxon–Mann–Whitney tests evaluated inter-group differences, whereas Cox regression analysis assessed prognostic factors. Results: Fifty females and fifty males, with a median age of 69 years, received 107 SRTs. A total of 213 BM (range, 1–10 per treatment) with a median volume of 0.22 cc were irradiated with a median minimum BED of 59.5 Gy. The median delivered GTV D95 reduction was −0.3%. The median follow-up was 11 months. Nineteen LP events and a 1-year LC rate of 90.1% were observed. The GTV coverage did not correlate with LC, while the GTV volume was a risk factor for LP, with the 1-year rate dropping to 73% for volumes ≥ 0.88 cc. The median LPFS, IPFS, and OS were 6, 5, and 7 months, respectively. Multivariate analysis showed that patients with melanoma histology and those receiving a second or subsequent systemic therapy line had the worst outcomes, whereas patients with adenocarcinoma histology and mutations showed better results. Conclusions: The accuracy and efficacy of the Linac-based SRT approach for BM were confirmed, but the dose distribution alone failed to predict the treatment response, suggesting that other factors must be considered to maximize SRT outcomes. [ABSTRACT FROM AUTHOR]

Hereditary breast/ovarian cancer (HBOC) syndrome is caused by the inheritance of monoallelic germline BRCA1/2 gene mutations. If BRCA1/2 mutation carriers are identified before the disease develops, effective actions against HBOC can be taken, including intensive screening, risk-reducing mastectomy and salpingo-oophorectomy, and risk-reducing medications. The Italian National Prevention Plan mandates the creation of regional BRCA genetic testing programmes. So far, however, only informal data have been reported on their implementation. We have designed a study aimed at evaluating the results of a population-based programme for risk assessment and genetic counselling and testing for BRCA1/2-related HBOC that is underway in the Emilia-Romagna region (northern Italy). The programme—which is entirely free—includes basic screening with an estimate of the likelihood of carrying a BRCA1/2 mutation using a familial risk assessment tool, a closer examination of women with suspected risk increase, an assessment of the need for further genetic counselling and, if needed, genetic testing and risk-reducing interventions. In this paper, the design of the programme and the protocol of the study are presented. The study has an observational, historical cohort design. Eligible are the women found to be at an increased risk of HBOC (profile 3 women). The main objectives are (i) to determine the precision of the programme in measuring the level of risk of HBOC for profile 3 women; (ii) to determine the characteristics of profile 3 women and their association with the risk management strategy chosen; (iii) to compare the age at onset, histologic type, tumour stage, molecular subtype, and prognosis of breast/ovarian cancers observed in the cohort of profile 3 women with the features of sporadic cancers observed in the general female population; (iv) to determine the level and the determinants of adherence to recommendations; and (v) to determine the appropriateness and timing of risk-reducing surgery and medications. Investigating the quality and results of the programme is necessary because the best practices in risk assessment and genetic counselling and testing for BRCA1/2-related cancer and the challenges they encounter should be identified and shared. The study has the potential to provide sound empirical evidence for the factors affecting the effectiveness of this type of service. [ABSTRACT FROM AUTHOR]

Cancer cells modulate their metabolism, creating an acidic microenvironment that, in turn, can favor tumor progression and chemotherapy resistance. Tumor cells adopt strategies to survive a drop in extracellular pH (pHe). In the present manuscript, we investigated the contribution of mitochondrial sirtuin 3 (SIRT3) to the adaptation and survival of cancer cells to a low pHe. SIRT3-overexpressing and silenced breast cancer cells MDA-MB-231 and human embryonic kidney HEK293 cells were grown in buffered and unbuffered media at pH 7.4 and 6.8 for different times. mRNA expression of SIRT3 and CAVB, was measured by RT-PCR. Protein expression of SIRT3, CAVB and autophagy proteins was estimated by western blot. SIRT3-CAVB interaction was determined by immunoprecipitation and proximity ligation assays (PLA). Induction of autophagy was studied by western blot and TEM. SIRT3 overexpression increases the survival of both cell lines. Moreover, we demonstrated that SIRT3 controls intracellular pH (pHi) through the regulation of mitochondrial carbonic anhydrase VB (CAVB). Interestingly, we obtained similar results by using MC2791, a new SIRT3 activator. Our results point to the possibility of modulating SIRT3 to decrease the response and resistance of tumor cells to the acidic microenvironment and ameliorate the effectiveness of anticancer therapy. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae strains that are resistant to multiple drugs (KPMDRs), which are often acquired in hospital settings and lead to healthcare-associated infections, pose a serious public health threat, as does hypervirulent K. pneumoniae (hvKp), which can also cause serious infections in otherwise healthy individuals. The widespread and often unnecessary use of antibiotics seen during the recent COVID-19 pandemic has exacerbated the challenges posed by antibiotic resistance in clinical settings. There is growing concern that hypervirulent (hvKp) strains may acquire genes that confer antimicrobial resistance, thus combining an MDR profile with their increased ability to spread to multiple body sites, causing difficult-to-treat infections. This study aimed to compare resistance and virulence profiles in KPC-3-producing K. pneumoniae isolates collected over four years (2020–2023). A genome-based surveillance of all MDR CRE-K. pneumoniae was used to identify genetic differences and to characterize the virulence and resistance profiles. Our results provide a picture of the evolution of resistance and virulence genes and contribute to avoiding the possible spread of isolates with characteristics of multi-drug resistance and increased virulence, which are thought to be one of the main global challenges to public health, within our hospital. [ABSTRACT FROM AUTHOR]

Background: Parents of children with chronic conditions face challenges that go beyond basic care and parenting responsibilities. Parents' experiences can be influenced by perceived stress, emotional experiences, feelings of helplessness, low sense of self-efficacy, anxiety and depression, reducing their quality of life. It is therefore not surprising that parents of children with chronic illnesses are more likely to experience stress, anxiety and depression than parents of healthy children. A prevalent chronic condition is type 1 diabetes. Methods: Parents (31 with children with type 1 diabetes diagnosis and 71 with children without chronic illness) were recruited to complete the measures of the Brief Symptom Inventory-18 (BSI-18), the Parent Health Locus of Control (PHLOC) and Parenting Sense of Competence (PSOC). Results: Significant differences in depression and internal locus of control were found; there was a positive correlation between internal LOC and efficacy in both samples; furthermore, there was a negative correlation between somatization and satisfaction in the experimental group. Conclusions: The ongoing experiences and challenges faced daily make parents perceive themselves as capable. Active involvement in supporting and managing the needs of child with type 1 diabetes could be a source of empowerment for the parent, contributing to the maintenance of their sense of competence. It is important, therefore, to consider the well-being and perception of the parent at a personal level, regardless of the child's situation. [ABSTRACT FROM AUTHOR]

Episodes of direct violence against healthcare workers and social workers represent a worrying and widespread phenomenon in Western countries. These violent attacks, whether verbal or physical, occur in various work environments, targeting professionals working in private facilities, medical practices, or those employed within the National Health System facilities. We conducted a search using a single search engine (PubMed) using the terms "violence against healthcare workers AND Western" for the period 2003–2023, identifying 45 results to which we added to the literature through hand searching. Our review thus analyzed the sector literature to highlight the phenomenon of violence against healthcare workers, particularly in Western countries. We began with an analysis of the problem and then focused on the true purpose of the study, which is to propose new solutions to protect healthcare workers in all work settings. Consequently, we aim to improve both the working environment for healthcare professionals and to enhance the overall healthcare and public health outcomes. [ABSTRACT FROM AUTHOR]

Sonoporation has garnered significant attention for its potential to temporarily permeabilize cell membranes through the application of ultrasound waves, thus enabling an efficient cellular uptake of molecules. Despite its promising applications, the precise control of sonoporation remains a complex and evolving challenge in the field of cellular and molecular biology. This review aims to address two key aspects central to advancing our understanding of sonoporation. Firstly, it underscores the necessity for the establishment of a standardized methodology to validate and quantify the successful entry of molecules into target cells. This entails a critical examination of existing techniques and the identification of best practices to ensure accurate, reliable, and reproducible results. By establishing a common framework for assessing sonoporation outcomes, researchers can enhance the reliability and comparability of their experiments, paving the way for more robust findings. Secondly, the review places particular emphasis on the detailed analysis of various acoustic parameters as reported in the papers selected from the literature. Among these parameters, acoustic intensity (specifically, ISPTA) emerges as a pivotal factor in sonoporation studies. Furthermore, this review delves into the exploration of the elastic modulus and its significance in sonoporation mechanisms and associated challenges. This knowledge can inform the development of more effective strategies to optimize sonoporation protocols. In summary, this review not only highlights the pressing need for a standardized approach to verify molecule entry into cells but also delves into the search for an effective frequency and acoustic intensity for in vivo and in vitro applications. [ABSTRACT FROM AUTHOR]

Screen time refers to the amount of time a child is exposed to a screen, that is, television, computer, smartphone, or any other digital medium. Prolonged screen time in the first years of life may affect a child's cognitive abilities, especially language acquisition. A systematic review was conducted, following the PRISMA-P guidelines, with the aim to explore the available literature relating to the impact of screen time on children's language development. This review identified 18 articles. The articles reviewed showed that prolonged screen time and exposure to screens in the first 2 years of life can negatively affect language development and communication skills, in terms of comprehension and vocabulary range. In addition, overexposure to screens in the early years can affect overall cognitive development, especially attention to environmental stimuli, social experiences, problem solving, and communication with others, e.g., the alternance of rhythms and roles in a conversation. In conclusion, our systematic review supports the idea that preschool screen time has negative effects on children's cognitive and language development. Television seems to be the medium most detrimental to children's skills, as it is used in a passive manner and is often characterised by language and content that do not suit the child's processing mode. Future studies should increasingly focus on the digital media that children possess at an early age, such as mobile phones and tablets, and on how children relate to the online world, such as social networks. [ABSTRACT FROM AUTHOR]

Simple Summary: Stereotactic body radiation therapy (SBRT) can be safely delivered for the treatment of localized prostate cancer. High-dose-per-fraction treatments require precise and rapid delivery of the radiation dose to the tumor, and any potential margin expansion must be balanced against the risk of increased toxicity. Since significant intrafraction prostate displacement can have a relevant impact on an extreme-hypofractionated regimen, real-time monitoring has emerged as a strategy to avoid the excessive exposure of healthy tissue or insufficient target coverage, but it requires continuous investment of resources and time. In real-world clinical practice, the utilization of organ motion management devices is not always feasible for all patients. Thus, our strategy has often been to mitigate the impact of intrafraction motion by shortening the delivery time without compromising the quality of the treatment. This was achieved through optimal patient preparation, flattening filter-free (FFF) beams, adequate margins, and a reduction in the number of arcs in the VMAT technique. This study aimed to comprehensively present data on treatment optimization in linac-based SBRT for localized prostate cancer at a single institution. Moreover, the dosimetric quality and treatment efficiency of single-arc (SA) versus dual-arc (DA) VMAT planning and delivery approaches were compared. Re-optimization was performed on twenty low-to-intermediate-risk- (36.25 Gy in 5 fractions) and twenty high-risk (42.7 Gy in 7 fractions) prostate plans initially administered with the DA FFF-VMAT technique in 2021. An SA approach was adopted, incorporating new optimization parameters based on increased planning and clinical experience. Analysis included target coverage, organ-at-risk (OAR) sparing, treatment delivery time, and the pre-treatment verification's gamma analysis-passing ratio. The SA optimization technique has consistently produced superior plans. Rectum and bladder mean doses were significantly reduced, and comparable target coverage and homogeneity were achieved in order to maintain a urethra protection strategy. The mean SA treatment delivery time was reduced by 22%; the mean monitor units increased due to higher plan complexity; and dose measurements demonstrated optimal agreement with calculations. The substantial reduction in treatment delivery time decreased the probability of prostate motion beyond the applied margins, suggesting potential decrease in treatment-related toxicity and improved target coverage in prostate SBRT. Further investigations are warranted to assess the long-term clinical outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: This systematic review focuses on the occurrence of fish-borne zoonotic helminths, including Clinostomum complanatum, Contracaecum rudolphii, Dibothriocephalus latus, Eustrongylides excisus, Opisthorchis felineus, and Pseudamphistomum truncatum, in freshwater fish populations of Italy and neighbouring countries. The study outlines the biological aspects and investigates the factors involved in the geographical expansion of these parasitic species. By synthesizing existing knowledge, we aim to compile epidemiological information concerning fish-borne zoonotic helminths and highlight the consumer risks. In conclusion, we encourage a One-Health approach in the context of food safety among EU countries to manage sanitary issues of all fish-borne zoonoses. In recent years, the consumption of fish products has surged in European countries, being an essential part of a healthy diet. Despite representing a small part of EU production, freshwater fisheries hold considerable significance for lake-dwelling populations and tourists seeking traditional dishes. This increased fish consumption has brought to light potential health risks associated with fish-borne zoonotic helminths (FBZHs), now acknowledged as global food-borne parasites. Fish-borne zoonotic helminths belong to various taxonomic groups, including nematodes (Anisakidae), trematodes (Opisthorchiidae and Heterophyidae), and cestodes (Diphyllobothriidae). More than 50 species of FBZH are known to cause human infections, derived from eating raw or undercooked aquatic foods containing viable parasites. Despite increased attention, FBZHs remain relatively neglected compared to other food-borne pathogens due to factors like chronic disease progression and under-diagnosis. This systematic review concentrates on the prevalence of six freshwater FBZHs (Clinostomum complanatum, Contracaecum rudolphii, Dibothriocephalus latus, Eustrongylides excisus, Opisthorchis felineus, and Pseudamphistomum truncatum) in Italy and neighbouring countries. The study explores the expansion of these parasites, analysing their biological and epidemiological aspects, and the factors that influence their proliferation, such as the increased cormorant population and the lake eutrophication phenomena. In summary, this research highlights the necessity for further research, the development of spatial databases, and the establishment of a unified European policy to effectively manage these multifaceted health concerns. It strongly advocates adopting a One-Health approach to address the growing incidence of parasitic zoonoses within the context of food safety in EU countries. [ABSTRACT FROM AUTHOR]

The Sars-CoV-2 pandemic has had important economic, health, political, and jurisprudential implications all over the world. According to innovations already introduced by Law 24/2017, with Decree Law no. 44 of 1 April 2021 and the subsequent conversion law no. 71 of 2021, Italy is the only country in which ad hoc rules have been introduced to limit the professional liability of healthcare professionals during the health emergency. The "criminal shield" can be defined as the Legislator response to the extreme pressure on healthcare professionals during the pandemic. [ABSTRACT FROM AUTHOR]

Simple Summary: Stereotactic radiosurgery (SRS) and fractionated SRS (fSRS) for brain metastases (BM) have become the standard of care for patients with up to 10 BM, yielding similar survival but a lower risk of long-term neurocognitive decline than whole-brain radiotherapy (WBRT). New technologies have allowed the accurate delivery of these high doses to the target using linac-based frameless techniques, and single-isocenter multiple-target (SIMT) approaches have recently been adopted for the simultaneous treatment of all BM. However, residual setup errors combined with intrafraction head motion may result in non-negligible compromised target coverage. While many groups have evaluated the efficacy of linac-based treatments using multiple and non-coplanar arcs, to our knowledge, only a few studies have presented clinical experience with coplanar arcs. Therefore, the present study aims to report our institutional investigation about the accuracy and outcomes of single-isocenter VMAT SRS treatments for both single and multiple BM delivered using only coplanar arcs and kV-CBCT as an IGRT system. The efficacy of linac-based SRS/fSRS treatments using the single-isocenter coplanar FFF-VMAT technique for both single and multiple BM was investigated. Seventy patients (129 BM) treated with 15–21 Gy in 1 (n = 59) or 27 Gy in 3 (n = 11) fractions were analyzed. For each fraction, plans involving the intra-fractional errors measured by post-treatment CBCT were recalculated. The relationships of BM size, distance-to-isocenter, and barycenter shift with the difference in target coverage were evaluated. Clinical outcomes were assessed using logistic regression and Kaplan-Meier analysis. The median delivery time was 3.78 min (range, 1.83–9.25). The median post-treatment 3D error was 0.5 mm (range, 0.1–2.7) and the maximum rotational error was 0.3° (range, 0.0–1.3). In single BM patients, the GTV D95% was never reduced by >5%, whereas PTV D95% reductions >1% occurred in only 11 cases (29%). In multiple BM patients, dose deficits >5% and >1% occurred in 2 GTV (2%) and 34 PTV (37%), respectively. The differences in target coverage showed a moderate-to-strong correlation only with barycenter shift. Local failure of at least one treated BM occurred in 13 (21%) patients and the 1-year and 2-year local control rates for all lesions were 94% and 90%, respectively. The implemented workflow ensured that the degradation of target and brain dose metrics in delivered treatments was negligible. Along with encouraging clinical outcomes, these findings warrant a reduction in the PTV margins at our institution. [ABSTRACT FROM AUTHOR]

Subjects with pathogenic (PV) and likely pathogenic (LPV) FLCN variants have an increased risk of manifesting benign and malignant disorders that are related to Birt–Hogg–Dubé syndrome (BHDS): an autosomal dominantly inherited disorder whose severity can vary significantly. Renal cell carcinoma (RCC) development in BHD (Birt–Hogg–Dubé) patients has a very high incidence; thus, identifying this rare syndrome at early stages and preventing metastatic spread is crucial. Over the last decade, the advancement of Next Generation Sequencing (NGS) and the implementation of multigene panels for hereditary cancer syndromes (HCS) have led to a subsequent focus on additional genes and variants, including those of uncertain significance (VUS). Here, we describe a novel FLCN variant observed in a subject manifesting disorders that were suspected to be related to BHDS and with a family history of multiple cancers. [ABSTRACT FROM AUTHOR]

Introduction: Specific Learning Disorder (SLD) is a neurodevelopmental disorder characterized by difficulties in perceiving and processing verbal and non-verbal information. It is usually accompanied by impaired academic skills leading to school dropout and emotional disturbances, resulting in significant distress and behavioral problems. Methods: A cognitive, academic, and emotional-behavioral assessment was performed at T0 and T1 in children and adolescents with SLD. Participants received psychotherapy and speech therapy treatment from T0 to T1. Results: In SLD, the most compromised cognitive functions were working memory and writing skills. An impact on academic abilities was found. Children and adolescents with SLD experience greater anxiety and depression levels compared to their control peers. Conclusions: SLD may adversely influence psychological well-being. To counteract such a consequence, more specific cognitive and academic skill-oriented strategies should be taken into consideration. [ABSTRACT FROM AUTHOR]

Simple Summary: Porcine Reproductive and Respiratory Syndrome (PRRS) is an infectious disease of viral etiology characteristic of the swine species. Although almost three decades have passed since its emergence, control of the disease still presents significant issues, representing a source of concern for veterinarians and breeders. In addition to management difficulties, the PRRS virus (PRRSV) causes severe economic losses in terms of abortions, a decrease in animal growth, increased mortality, and the massive use of drugs. Understanding the genetic markers involved in the response to the infection is challenging and crucial and represents the main goal of this study. CD163, which encodes the membrane receptor used by the PRRSV to enter macrophages and initiate infection, has been identified as one of the most promising marker genes associated with genetic susceptibility to the disease. In this study, detection by sequencing of the more significant polymorphisms on the CD163 gene was conducted for the first time on 377 pigs reared in different farms distributed in some areas of Central Italy. The genotyping data obtained in this work, together with the assessment of the virological status of the animals and the comparison with the findings from other PRRSV conditioned and experimental infection trials, will allow a better understanding of whether some Italian pig populations can represent a good genetic resource and a reservoir of resistance/"resilience" markers to PRRS. Indeed, marker-assisted selection (MAS) could represent an alternative and a more valid tool than vaccination to control the spread of this impactful disease. Porcine Reproductive and Respiratory Syndrome (PRRS) caused by the PRRS virus affects farmed pigs worldwide, causing direct and indirect losses. The most severe manifestations of PRRS infection are observed in piglets and pregnant sows. The clinical outcome of the infection depends on the PRRSV strain's virulence, the pregnancy state of the female, environmental factors, the presence of protective antibodies due to previous infections, and the host's genetic susceptibility. The latter aspect was investigated in this study, in particular, evaluating the most significant polymorphisms (SNPs) of the CD163 gene in slaughtered pigs reared in Central Italy. Total RNAs were extracted from 377 swine samples and subjected to RT-PCR targeted to the CD163 gene, followed by sequencing analysis. Contextually, the viral RNA was detected by RT-qPCR in order to phenotypically categorize animals into infected and not infected. In particular, 36 haplotypes were found, and their frequencies ranged from 0.13% to 35.15%. There were 62 resulting genotypes, three of which were associated with a putative resistance to the disease. Both the haplotypes and genotypes were inferred by PHASE v.2.1 software. To the best of our knowledge, this type of investigation was conducted for the first time on pig livestock distributed in different regions of Central Italy. Thus, the obtained findings may be considered very important since they add useful information about swine genetic background in relation to PRRS infection, from the perspective of adopting Marker-Assisted Selection (MAS) as a possible and alternative strategy to control this still widespread disease. [ABSTRACT FROM AUTHOR]

Background: The axilla is a region of fundamental importance for the implications during oncological surgery, and there are many classifications of axillary lymph node subdivision: on the basis of studies on women with breast cancer, we used Clough's and Li's classification. However, currently we do not have a gold-standard classification regarding axillary lymphatic drainage in melanoma patients. Purpose: Our aim was to evaluate how these classifications could be adapted to sentinel lymph node evaluation in skin-melanoma patients and to look for a possible correlation between the most recent classifications of axillary lymph node location and Oeslner's classification, one of the most common anatomical classifications still widespread today. Methods: We analyzed data from 21 patients who underwent sentinel lymph node biopsy between January 2021 and January 2022. Results: Our study demonstrates that, to an extent, there is a possible difference in the use of the various classifications, hinting at possible limits of each. The data we obtained underline how cutaneous melanoma presents extremely heterogenous lymphatic drainage at the level of the axillary cavity. However, the limited data in our possession do not allow us to obtain, at the moment, results that are statistically significant, although we are continuing to enroll patients and collect data. Conclusions: Results of this study support the evidence that the common classifications used for breast cancer do not seem to be exhaustive. Therefore, a specific axillary lymph node classification is necessary in skin melanoma patients. [ABSTRACT FROM AUTHOR]

Formaldehyde (FA) is a toxic compound and a human carcinogen. Regulating FA-releasing substances in commercial goods is a growing and interesting topic: worldwide production sectors, like food industries, textiles, wood manufacture, and cosmetics, are involved. Thus, there is a need for sensitive, economical, and specific FA monitoring tools. Solid-phase microextraction (SPME), with O-(2,3,4,5,6-pentafluorobenzyl)-hydroxylamine (PFBHA) on-sample derivatization and gas chromatography, is proposed for FA monitoring of real-life samples. This study reports the use of polydimethylsiloxane (PDMS) as a sorbent phase combined with innovative commercial methods, such as multiple SPME (MSPME) and cooling-assisted SPME, for FA determination. Critical steps, such as extraction and sampling, were evaluated in method development. The derivatization was performed at 60 °C for 30 min, followed by 15 min sampling at 10 °C, in three cycles (SPME Arrow) or six cycles (SPME). The sensitivity was satisfactory for the method's purposes (LOD-LOQ at 11-36 ng L−1, and 8-26 ng L−1, for SPME and SPME Arrow, respectively). The method's linearity ranges from the lower LOQ at trace level (ng L−1) to the upper LOQ at 40 mg L−1. The precision range was 5.7–10.2% and 4.8–9.6% and the accuracy was 97.4% and 96.3% for SPME and SPME Arrow, respectively. The cooling MSPME set-up applied to real commercial goods provided results of quality comparable to previously published data. [ABSTRACT FROM AUTHOR]

Upper limb exoskeletons may confer significant mechanical advantages across a range of tasks. The potential consequences of the exoskeleton upon the user's sensorimotor capacities however, remain poorly understood. The purpose of this study was to examine how the physical coupling of the user's arm to an upper limb exoskeleton influenced the perception of handheld objects. In the experimental protocol, participants were required to estimate the length of a series of bars held in their dominant right hand, in the absence of visual feedback. Their performance in conditions with an exoskeleton fixed to the forearm and upper arm was compared to conditions without the upper limb exoskeleton. Experiment 1 was designed to verify the effects of attaching an exoskeleton to the upper limb, with object handling limited to rotations of the wrist only. Experiment 2 was designed to verify the effects of the structure, and its mass, with combined movements of the wrist, elbow, and shoulder. Statistical analysis indicated that movements performed with the exoskeleton did not significantly affect perception of the handheld object in experiment 1 (BF01 = 2.3) or experiment 2 (BF01 = 4.3). These findings suggest that while the integration of an exoskeleton complexifies the architecture of the upper limb effector, this does not necessarily impede transmission of the mechanical information required for human exteroception. [ABSTRACT FROM AUTHOR]

In this study we evaluated both~ K- and N-RAS mutations in plasma samples from patients with metastatic colorectal cancer by means of the BEAMing technology, and we assessed their diagnostic performance compared to RAS analyses performed on tissue. The sensitivity of BEAMing in identifying KRAS mutations was of 89.5%, with a fair specificity. The agreement with tissue analysis was moderate. The sensitivity for NRAS was high with a good specificity, and the agreement between tissue analysis and BEAMing was fair. Interestingly, significantly higher mutant allele fraction (MAF) levels were detected in patients with G2 tumors, liver metastases, and in those who did not receive surgery. NRAS MAF level was significantly higher in patients with mucinous adenocarcinoma and for those with lung metastases. A sharp increase in the MAF values was observed in patients who moved towards disease progression. More strikingly, molecular progression always anticipated the radiological one in these patients. These observations pave the way to the possibility of using liquid biopsy to monitor patients during treatment, and to enable oncologists to anticipate interventions compared to radiological analyses. This will allow time to be saved and ensure a better management of metastatic patients in the near future. [ABSTRACT FROM AUTHOR]

Sonic hedgehog medulloblastoma (SHH-MB) accounts for 25–30% of all MBs, and conventional therapy results in severe long-term side effects. New targeted therapeutic approaches are urgently needed, drawing also on the fields of nanoparticles (NPs). Among these, plant viruses are very promising, and we previously demonstrated that tomato bushy stunt virus (TBSV), functionalized on the surface with CooP peptide, specifically targets MB cells. Here, we tested the hypothesis that TBSV-CooP can specifically deliver a conventional chemotherapeutic drug (i.e., doxorubicin, DOX) to MB in vivo. To this aim, a preclinical study was designed to verify, by histological and molecular methods, if multiple doses of DOX-TBSV-CooP were able to inhibit tumor progression of MB pre-neoplastic lesions, and if a single dose was able to modulate pro-apoptotic/anti-proliferative molecular signaling in full-blown MBs. Our results demonstrate that when DOX is encapsulated in TBSV-CooP, its effects on cell proliferation and cell death are similar to those obtained with a five-fold higher dose of non-encapsulated DOX, both in early and late MB stages. In conclusion, these results confirm that CooP-functionalized TBSV NPs are efficient carriers for the targeted delivery of therapeutics to brain tumors. [ABSTRACT FROM AUTHOR]

Simple Summary: The interaction of nanomaterials with pollutants in the marine environment might alter bioavailability, as well as toxicity, of both nanomaterials and pollutants, representing a risk, not only for marine organisms, but also for consumers through the marine food chain. The aim of this research was to study whether titanium dioxide nanoparticles affect bioaccumulation and toxicity of pollutants, such as non-dioxin-like polychlorinated biphenyls in edible mussels harvested in a controlled contaminated environment. The results highlighted that titanium dioxide nanoparticles do not affect non-dioxin-like polychlorinated biphenyls' accumulation in mussels, as their concentration was comparable with or without nanoparticles. Titanium dioxides nanoparticles in combination with non-dioxin-like polychlorinated biphenyls amplified the toxic effect on mussels compared to the exposure of non-dioxin-like polychlorinated biphenyls. Finally, mussels were submitted to a seven-day depuration process to evaluate the elimination of accumulated chemicals. Most titanium dioxide nanoparticles were eliminated after depuration, and their presence had a synergistic effect on non-dioxin-like polychlorinated biphenyls, which were eliminated in a greater quantity compared to mussels exposed only to non-dioxin-like polychlorinated biphenyls. In any case, consumers might be exposed to TiO2NPs and ndl-PCBs (both concurrently and separately) if edible mussels, harvested in a contaminated environment, are consumed without a proper depuration process. The interaction of nanomaterials with pollutants in the marine environment might alter bioavailability, as well as toxicity, of both nanomaterials and pollutants, representing a risk, not only for marine organisms, but also for consumers through the marine food chain.The aim of this study was to evaluate the effect of titanium dioxide nanoparticles (TiO2NPs) in terms of bioaccumulation and toxicity on Mediterranean mussels (Mytilus galloprovincialis) exposed to six-indicator non-dioxin-like polychlorinated biphenyls (ndl-PCBs). Mussels were exposed to ndl-PCBs (20 µg/mL) (groups 3–4) or to a combination of ndl-PCBs (20 µg/mL) and TiO2NPs (100 µg/mL) (groups 5–6) for four consecutive days. TiO2NPs was detected in groups 5–6 (3247 ± 567 and 1620 ± 223 µg/kg respectively), but their presence did not affect ndl-PCBs bioaccumulation in mussels. In fact, in groups 3–4, the concentration of ndl-PCBs (ranging from 3818.4 ± 166.0–10,176 ± 664.3 µg/kg and 2712.7 ± 36.1–9498.0 ± 794.1 µg/kg respectively) was not statistically different from that of groups 5–6 (3048.6 ± 24.0–14,635.9 ± 1029.3 and 5726.0 ± 571.0–9931.2 ± 700.3 µg/kg respectively). Histological analyses showed alterations to the structure of the gill tissue with respect to the control groups, with more severe and diffuse dilatation of the central hemolymphatic vessels of the gill lamellae in groups 5–6 (treated with TiO2NPs and ndl-PCBs concurrently) compared to groups 3–4 (ndl-PCBs only). Finally, in mussels submitted to a seven-day depuration process, most TiO2NPs were eliminated, and NPs had a synergistic effect on ndl-PCBs elimination; as a matter of fact, in groups 5–6, the percentage of concentration was statically inferior to the one observed in groups 3–4. In any case, consumers might be exposed to TiO2NPs and ndl-PCBs (both concurrently and separately) if edible mussels, harvested in a contaminated environment, are consumed without a proper depuration process. [ABSTRACT FROM AUTHOR]

Simple Summary: Hereditary pathogenic/likely-pathogenic variants (PVs/LPVs) of BRCA1 and BRCA2 genes are the principal genetic cause of breast cancer (BC), ovarian cancer (OC), and other malignancies such as prostate (PrC) and pancreas (PC) carcinomas. The proportion of BRCA1 vs. BRCA2 is specific to various populations in different regions, and several PVs have been observed to be founders, besides recurring in narrow geographical areas. In our study, in a selected cohort of subjects characterized by a common local origin and a cancer family history, we identified a BRCA2 PV that was further analyzed and correlated to the risk of PC onset. PVs and LPVs in BRCA1/2 genes are correlated to a high risk of developing breast cancer and/or ovarian cancer (Hereditary Breast and Ovarian Cancer syndrome, HBOC); additionally, in recent years, an increasing number of BRCA 1/2 variants have been identified and associated with pancreatic cancer. Epidemiologic studies have highlighted that inherited factors are involved in 10% to 20% of PCs, mainly through deleterious variants of BRCA2. The frequency of BRCA1/2 germline alterations fluctuates quite a lot among different ethnic groups, and the estimated rate of PVs/LPVs variants in Italian HBOC families is not very accurate, according to different reports. The aim of our study is to describe the prevalence of a BRCA2 PV observed in a selected cohort of HBOC patients and their relatives, whose common origin is the eastern coast of Emilia Romagna, a region of Italy. This study provides insight into the frequency of the variant detected in this area and provides evidence of an increased risk of pancreatic and breast cancer, useful for genetic counseling and surveillance programs. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers and is forecasted to become the second most common cause of cancer-related deaths by 2030. Its therapy has proven extremely difficult and, consequently, there is an urgent need for novel therapeutic strategies for PDAC. Although Gemcitabine chemotherapy has long been used as a standard of care for PDAC, it suffers from limited efficacy and high toxicity. Here, we describe a new therapeutic strategy based on a single chain bispecific antibody (scDb-hERG1-β1) which targets a cancer-specific antigen, i.e., the complex formed by the K+ channel hERG1 and the β1 integrin (hERG1/β1 integrin complex). The combination of scDb-hERG1-β1 with sub-optimal doses of Gemcitabine in mice implanted with PDAC showed good therapeutic efficacy, low toxicity and, consequently, prolonged survival time. Our data pave the way for improving the therapy of PDAC, and possibly other cancers, by combining chemotherapy with ion channel modulators. Pancreatic ductal adenocarcinoma (PDAC) represents an unmet medical need. Difficult/late diagnosis as well as the poor efficacy and high toxicity of chemotherapeutic drugs result in dismal prognosis. With the aim of improving the treatment outcome of PDAC, we tested the effect of combining Gemcitabine with a novel single chain bispecific antibody (scDb) targeting the cancer-specific hERG1/β1 integrin complex. First, using the scDb (scDb-hERG1-β1) in immunohistochemistry (IHC), Western blot (WB) analysis and immunofluorescence (IF), we confirmed the presence of the hERG1/β1 integrin complex in primary PDAC samples and PDAC cell lines. Combining Gemcitabine with scDb-hERG1-β1 improved its cytotoxicity on all PDAC cells tested in vitro. We also tested the combination treatment in vivo, using an orthotopic xenograft mouse model involving ultrasound-guided injection of PDAC cells. We first demonstrated good penetration of the scDb-hERG1-β1 conjugated with indocyanine green (ICG) into tumour masses by photoacoustic (PA) imaging. Next, we tested the effects of the combination at either therapeutic or sub-optimal doses of Gemcitabine (25 or 5 mg/kg, respectively). The combination of scDb-hERG1-β1 and sub-optimal doses of Gemcitabine reduced the tumour masses to the same extent as the therapeutic doses of Gemcitabine administrated alone; yielded increased survival; and was accompanied by minimised side effects (toxicity). These data pave the way for a novel therapeutic approach to PDAC, based on the combination of low doses of a chemotherapeutic drug (to minimize adverse side effects and the onset of resistance) and the novel scDb-hERG1-β1 targeting the hERG1/β1 integrin complex as neoantigen. [ABSTRACT FROM AUTHOR]

We investigated the presence and diversity of cetaceans in the Mediterranean Sea, analysing the data collected by 32 different research units, over a period of 15 years (2004–2018), and shared on the common web-GIS platform named Intercet. We used the encounter rate, the species prevalence, and the Shannon diversity index as parameters for data analysis. The results show that cetacean diversity, in the context of the Mediterranean basin, is generally quite low when compared with the eastern Atlantic, as few species, namely the striped dolphin, the bottlenose dolphin, the fin whale, and the sperm whale, dominate over all the others. However, some areas, such as the Alboran Sea or the north-western Mediterranean Sea, which includes the Pelagos Sanctuary (the Specially Protected Area of Mediterranean Interest located in the northern portion of the western basin), show higher levels of diversity and should be considered hotspots to be preserved. Primary production and seabed profile seem to be the two main drivers influencing the presence and distribution of cetaceans, with the highest levels of diversity observed in areas characterized by high levels of primary production and high bathymetric variability and gradient. This collective work underlines the importance of data sharing to deepen our knowledge on marine fauna at the scale of the whole Mediterranean Sea and encourages greater efforts in the networking process, also to accomplish the requirements of the Marine Strategy Framework Directive, with particular reference to Descriptor 1: biological diversity is maintained. [ABSTRACT FROM AUTHOR]

Noise exposure may cause auditory and extra-auditory effects. School teachers and students are exposed to high noise levels which have an impact on perceptual-cognitive and neurobehavioral aspects. The latter influence teaching conditions and student school performance. A Protocol was defined and parameters to be investigated were identified for acoustic characterization of unoccupied and occupied school environments, assessment of users by means of questionnaires completed by teachers and students, and vocal effort evaluation. Classrooms, laboratories, auditoriums, gymnasiums, common areas, canteens and outdoor areas were analysed in terms of acoustic features and identification of the origin of noise. The Protocol was tested in three kindergartens, three primary schools and three secondary schools placed in Rome, Florence and Perugia. Results of nine case studies are presented, including comparisons of objective and subjective investigations. Generally, the acoustic performances of the spaces under investigation do not meet the requirements of current Italian legislation. In particular, student activity determines high noise levels in laboratories, gymnasiums, and canteens. Students notice that noise mainly causes loss of concentration, fatigue, boredom, and headache. The outcomes of this research will be the starting point to define strategies and solutions for noise control and mitigation in schools and to draft guidelines for the acoustical school design. [ABSTRACT FROM AUTHOR]

WHO identifies vaccine hesitancy (VH) as one of the ten threats to global health. The authors bring to the international scientific community an Italian episode that offers the opportunity to renew the discussion on the extent of the VH matter. The purpose of this systematic review is to analyze the factors determining vaccine hesitancy in the Italian population, to understand its roots, and suggest potential strategies to mitigate it. A systematic review of the literature according to the PRISMA guidelines was carried out using the SCOPUS and Medline (via PubMed) databases, using the following strategy: (COVID-19 vaccines) AND (vaccination hesitancy) AND (Italy). After the selection process, 36 articles were included in this systematic review. The most frequently detected factors associated with VH in the Italian population can be grouped as vaccine-related factors, socio-cultural factors, and demographic factors. Currently, we are facing a gap between the population and science, governments, and institutions. To heal this breach, it is necessary to strengthen the trust of the population through the implementation of health communication and public education strategies, while scientific literacy must continue to support families and individuals in discerning evidence from opinions to recognize the real risks and balance them with the benefits. [ABSTRACT FROM AUTHOR]

Importation and translocation of seeds and live animals for aquaculture purposes are well-established practices in the European and Italian shellfish market. However, these routines may be responsible for alien species introduction and spread, representing a risk for aquaculture activities, human health, as well as for environmental and biodiversity conservation. To estimate and reduce the potential impact of alien and locally absent species on aquatic habitats due to aquaculture practices, Member States have adopted Council Regulation (EC) No 708/2007, which provides guidance for risk analysis and contingency measures for mitigation. Despite this legal framework, traceability data for shellfish movements are currently lacking and need to be improved in all EU Member States. The present work presents an updated literature summary of alien species associated with bivalve farming and trading. The information herein collected will be helpful to upgrade the traceability system of farmed bivalves in Italian marine waters with reference to non-target species, representing a knowledge baseline for setting bio security plans to reduce their risk of introduction and further spreading. [ABSTRACT FROM AUTHOR]

Simple Summary: With an ever-growing acceptance by the radiation oncology community, stereotactic body radiation therapy (SBRT) has become an increasingly common option for localized prostate cancer in recent years. However, such high doses per fraction require the specific management of the inter- and intrafraction movements of the target. In this work, synchronized motion-inclusive dose distributions using intrafraction motion data provided by a novel electromagnetic transmitter-based device were reconstructed and recomputed on deformed CTs reflecting the CBCT daily anatomy to represent the actual delivered dose. To our knowledge, there have been no previously published studies where the dosimetric impact on the target and organs at risk (OARs) of both intrafraction prostate motion and interfraction anatomical changes was investigated together in dose-escalated linac-based SBRT. Moreover, treatments that would have been delivered without any organ motion management (non-gated) were simulated to also evaluate the dosimetric benefit of employing continuous monitoring, beam gating, and motion correction strategies. The dosimetric impact of intrafraction prostate motion and interfraction anatomical changes and the effect of beam gating and motion correction were investigated in dose-escalated linac-based SBRT. Fifty-six gated fractions were delivered using a novel electromagnetic tracking device with a 2 mm threshold. Real-time prostate motion data were incorporated into the patient's original plan with an isocenter shift method. Delivered dose distributions were obtained by recalculating these motion-encoded plans on deformed CTs reflecting the patient's CBCT daily anatomy. Non-gated treatments were simulated using the prostate motion data assuming that no treatment interruptions have occurred. The mean relative dose differences between delivered and planned treatments were −3.0% [−18.5–2.8] for CTV D99% and −2.6% [−17.8–1.0] for PTV D95%. The median cumulative CTV coverage with 93% of the prescribed dose was satisfactory. Urethra sparing was slightly degraded, with the maximum dose increased by only 1.0% on average, and a mean reduction in the rectum and bladder doses was seen in almost all dose metrics. Intrafraction prostate motion marginally contributed in gated treatments, while in non-gated treatments, further deteriorations in the minimum target coverage and bladder dose metrics would have occurred on average. The implemented motion management strategy and the strict patient preparation regimen, along with other treatment optimization strategies, ensured no significant degradations of dose metrics in delivered treatments. [ABSTRACT FROM AUTHOR]

Studies have indicated that air pollution, including surface-level ozone (O3), can significantly influence the risk of chronic diseases. To better understand the carcinogenic mechanisms of air pollutants and identify predictive disease biomarkers, we examined the association between traffic-related pollutants with DNA methylation alterations and bulky DNA adducts, two biomarkers of carcinogen exposure and cancer risk, in the peripheral blood of 140 volunteers—95 traffic police officers, and 45 unexposed subjects. The DNA methylation and adduct measurements were performed by bisulfite-PCR and pyrosequencing and 32P-postlabeling assay. Airborne levels of benzo(a)pyrene [B(a)P], carbon monoxide, and tropospheric O3 were determined by personal exposure biomonitoring or by fixed monitoring stations. Overall, air pollution exposure was associated with a significant reduction (1.41 units) in global DNA methylation (95% C.I. −2.65–0.04, p = 0.026). The decrement in ALU repetitive elements was greatest in the policemen working downtown (95% C.I. −3.23–−0.49, p = 0.008). The DNA adducts were found to be significantly increased (0.45 units) in the municipal officers with respect to unexposed subjects (95% C.I. 0.02–0.88, p = 0.039), mainly in those who were controlling traffic in downtown areas (95% C.I. 0.39–1.29, p < 0.001). Regression models indicated an increment of ALU methylation at higher B(a)P concentrations (95% C.I. 0.03–0.60, p = 0.032). Moreover, statistical models showed a decrement in ALU methylation and an increment of DNA damage only above the cut-off value of 30 µg/m3 O3. A significant increment of 0.73 units of IL-6 gene methylation was also found in smokers with respect to non-smokers. Our results highlighted the role of air pollution on epigenetic alterations and genotoxic effects, especially above the target value of 30 µg/m3 surface-level O3, supporting the necessity for developing public health strategies aimed to reduce traffic-related air pollution molecular alterations. [ABSTRACT FROM AUTHOR]

BRCA1 and BRCA2 are the most frequently mutated genes in ovarian cancer (OC) crucial both for the identification of cancer predisposition and therapeutic choices. However, germline variants in other genes could be involved in OC susceptibility. We characterized OC patients to detect mutations in genes other than BRCA1/2 that could be associated with a high risk of developing OC and permit patients to enter the most appropriate treatment and surveillance program. Next-generation sequencing analysis with a 94-gene panel was performed on germline DNA of 219 OC patients. We identified 34 pathogenic/likely pathogenic variants in BRCA1/2 and 38 in other 21 genes. The patients with pathogenic/likely pathogenic variants in the non-BRCA1/2 genes mainly developed OC alone compared to the other groups that also developed breast cancer or other tumors (p = 0.001). Clinical correlation analysis showed that the low-risk patients were significantly associated with platinum sensitivity (p < 0.001). Regarding PARP inhibitors (PARPi) response, the patients with pathogenic mutations in the non-BRCA1/2 genes had worse PFS and OS. Moreover, a statistically significantly worse PFS was found for every increase of one thousand platelets before PARPi treatment. To conclude, knowledge about molecular alterations in genes beyond BRCA1/2 in OC could allow for more personalized diagnostic, predictive, prognostic, and therapeutic strategies for OC patients. [ABSTRACT FROM AUTHOR]

Locus coeruleus (LC) neurons, with their extensive innervations throughout the brain, control a broad range of physiological processes. Several ion channels have been characterized in LC neurons that control intrinsic membrane properties and excitability. However, ERG (ether-à-go-go–related gene) K+ channels that are particularly important in setting neuronal firing rhythms and automaticity have not as yet been discovered in the LC. Moreover, the neurophysiological and pathophysiological roles of ERG channels in the brain remain unclear despite their expression in several structures. By performing immunohistochemical investigations, we found that ERG-1A, ERG-1B, ERG-2 and ERG-3 are highly expressed in the LC neurons of mice. To examine the functional role of ERG channels, current-clamp recordings were performed on mouse LC neurons in brain slices under visual control. ERG channel blockade by WAY-123,398, a class III anti-arrhythmic agent, increased the spontaneous firing activity and discharge irregularity of LC neurons. Here, we have shown the presence of distinct ERG channel subunits in the LC which play an imperative role in modulating neuronal discharge patterns. Thus, we propose that ERG channels are important players behind the changes in, and/or maintenance of, LC firing patterns that are implicated in the generation of different behaviors and in several disorders. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the feasibility of ultrahypofractionated radiotherapy to the prostate bed in patients with biochemical and/or clinical relapse following radical prostatectomy who were enrolled in the prospective, observational, multicentric POPART trial (NCT04831970). Methods: Patients with post-radical prostatectomy PSA levels of ≥0.1–2.0 ng/mL and/or local relapse at PSMA PET/CT or multiparametric MRI were treated with Linac-based SBRT on the prostate bed up to a total dose of 32.5 Gy in five fractions every other day (EQD21.5 = 74.2 Gy). Maximum acute toxicity was assessed using the Common Terminology Criteria for Adverse Events version 5 scale. International Consultation on Incontinence Questionnaire—Short Form (ICIQ-SF) and Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) scores were assessed at baseline and during the follow-up. Results: From April 2021 to June 2022, thirty men with a median age of 72 years (range 55–82) were enrolled in three centers. The median PSA level before RT was 0.30 ng/mL (range 0.18–1.89 ng/mL). At 3 months post-treatment, no GI or ≥2 GU side effects were reported; three patients (10%) experienced Grade 1 GU toxicity. No changes in ICIQ-SF or in the urinary domains of EPIC-CP were observed, while a transient worsening was registered in the bowel domain. At the same time point, all but two patients, who progressed distantly, were found to be biochemically controlled with a median post-treatment PSA level of 0.07 ng/mL (range 0–0.48 ng/mL). Conclusions: Our preliminary findings show that SBRT can be safely extended to the postoperative setting, without an increase in short-term toxicity or a significant decline in QoL. Long-term results are needed to confirm this strategy. [ABSTRACT FROM AUTHOR]

hERG1 potassium channels are widely expressed in human cancers of different origins, where they affect several key aspects of cellular behaviour. The present study was designed to evaluate the expression and clinical relevance of hERG1 protein in cancer tissues from patients suffering from neuroendocrine tumours (NETs) of ileal (iNETs) and pancreatic (pNETs) origin, with available clinicopathological history and follow-up. The study was carried out by immunohistochemistry with an anti-hERG1 monoclonal antibody. In a subset of samples, a different antibody directed against the hERG1/β1 integrin complex was also used. The analysis showed for the first time that hERG1 is expressed in human NETs originating from either the ileum or the pancreas. hERG1 turned out to have a prognostic value in NETs, showing (i) a statistically significant positive impact on OS of patients affected by ileal NETs, regardless the TNM stage; (ii) a statistically significant positive impact on OS of patients affected by aggressive (TNM stage IV) disease, either ileal or pancreatic; (iii) a trend to a negative impact on OS of patients affected by less aggressive (TNM stage I-III) disease, either ileal or pancreatic. Moreover, in order to evaluate whether ERG1 was functionally expressed in a cellular model of pNET, the INS1E rat insulinoma cell line was used, and it emerged that blocking ERG1 with a specific inhibitor of the channel (E4031) turned out in a significant reduction in cell proliferation. [ABSTRACT FROM AUTHOR]