Emerging therapeutic strategies in Lynch syndrome-associated colorectal cancer and the role of MMR testing.

Lynch syndrome is the most common hereditary cancer predisposition, accounting for 1-5% of colorectal cancer cases, and is driven by germline mutations in DNA mismatch repair genes. Despite established diagnostic criteria, such as the Amsterdam guidelines, Lynch syndrome remains largely underdiagnosed. To address this gap, universal tumour screening has been introduced for all newly diagnosed cases of colorectal cancer and endometrial cancer, significantly improving early detection.

Analysis of Social Genetic Effects on Pigs Fed With Automatic Feeders Using a Visit-Based Approach.

Social behaviour traits and their impact on feed efficiency are of particular interest in pig farming. The integration of automatic feeders enables the collection of multiple phenotypes for breeding purposes. The additive genetic and social genetic effect can be estimated considering all the visits to the feeder by modelling each visit independently in a 'visit-based approach'.

Elevated mortality risks associated with late diagnosis of cancer in individuals with psychiatric disorders?

Introduction: Considering the elevated cancer mortality in individuals with psychiatric conditions, possibly associated with late diagnosis, this study investigated cancer screening participation rates among patients under the care of four Trieste community mental health centers (CMHCs).

Methods: We conducted a retrospective cohort study on 1252 individuals with psychiatric disorders, retrieving their electronic health records up to December 2019. The study assessed participation rates in breast, cervical, and colorectal cancer screening programs.

Schwann Cell-Specific Ablation of Beclin 1 Impairs Myelination and Leads to Motor and Sensory Neuropathy in Mice.

The core component of the class III phosphatidylinositol 3-kinase complex, Beclin 1, takes part in different protein networks, thus switching its role from inducing autophagy to regulating autophagosomal maturation and endosomal trafficking. While assessed in neurons, astrocytes, and microglia, its role is far less investigated in myelinating glia, including Schwann cells (SCs), responsible for peripheral nerve myelination. Remarkably, the dysregulation in endosomal trafficking is emerging as a pathophysiological mechanism underlying peripheral neuropathies, such as demyelinating Charcot-Marie-Tooth (CMT) diseases.

IMMUNOREACT 9 metachronous rectal cancers have high HLA-ABC expression on healthy epithelium but a lower infiltration of CD3+ T cells than primary lesions.

Lynch syndrome is rarely associated with rectal cancer (RC) and thus, metachronous RC has been scarcely investigated. This study aimed to analyze the mucosal immune microenvironment in sporadic and metachronous RC. We analyzed the mucosal immune microenvironment in the 25 metachronous RCs present in the IMMUNOREACT 1 and 2 multicentre observational studies (624 patients).

IMMUNOREACT 8: Immune markers of local tumor spread in patients undergoing transanal excision for clinically N0 rectal cancer.

Background: Transanal excision of rectal cancer can be considered the definitive surgical treatment if the depth spread is T1 or lower, and the lesion is completely included within the resection margin. This study aims to analyze the immune microenvironment in healthy rectal mucosa as a possible predictor of tumor infiltration depth, lateral tumor spread, and recurrence of rectal cancer after transanal local excision.

Methods: This study is a subanalysis of data from the IMMUNOREACT 1 and 2 trials (NCT04915326 and NCT04917263, respectively) including all the patients who underwent transanal excision of rectal cancer.

Impact of ageing and disuse on neuromuscular junction and mitochondrial function and morphology: Current evidence and controversies.

Inactivity and ageing can have a detrimental impact on skeletal muscle and the neuromuscular junction (NMJ). Decreased physical activity results in muscle atrophy, impaired mitochondrial function, and NMJ instability. Ageing is associated with a progressive decrease in muscle mass, deterioration of mitochondrial function in the motor axon terminals and in myofibres, NMJ instability and loss of motor units.

When end of treatment situations challenge patient-centered care: a discussion paper proposing new theoretical insights.

Introduction: According to the Institute of Medicine patient-centered medicine is one of the six crucial dimensions of health care quality. Although the patient-centered care model is widely recognized for its ethical underpinnings and effectiveness, its practical implementation still raises challenges, especially in end-of-treatment situations. This discussion paper offers an overview of the challenges facing the physician-patient relationship in end-of-treatment situations.

Adsorption and mineralization of metalaxyl-m and chlorpyrifos in irrigated Mediterranean soil under the effects of salinity.

To evaluate the effects of salinity on the fate of pesticides in a Mediterranean irrigated system, experiments were carried out under laboratory conditions to determine the adsorption, desorption, and mineralization of chlorpyrifos (CPF) and metalaxyl-M (MET) in a soil sample from an irrigated field in northern Tunisia. Adsorption/desorption isotherms and mineralization kinetics data were obtained over a realistic range of salinities via batch equilibrium and incubation techniques. On the basis of the experimental results, MET has a lower sorption capacity than CPF does, and the adsorption data for both compounds were better fitted by the Freundlich equation, with K values of 0.

Animal-free safety assessment of chemicals: an innovation system perspective.

This perspective paper, which is the result of a collaborative effort between toxicologists and scholars in innovation and transition studies, presents a heuristic framework based on innovation system literature for understanding and appraising mission achievement to animal-free chemical safety assessment using New Approach Methodologies (NAMs). While scientific and technical challenges in this area are relatively well known, the recent establishment of missions and roadmaps to accelerate the acceptance and effective use of NAMs for chemical safety assessment raises new questions about how we can grasp the systemic nature of all changes needed in this transition. This includes recognising broader societal, institutional, and regulatory shifts necessary for NAM acceptance and uptake.

Trends in colorectal cancer surgical resection rates during the screening era: a retrospective study in Italy.

Background: Faecal immunochemical test (FIT)-based screening is effective in reducing colorectal cancer (CRC) incidence, but its sensitivity for proximal lesions remains low.

Objectives: We compared age-adjusted CRC surgical resection rates across anatomic sites (proximal colon, distal colon, rectum), age groups and sex over 20 years in a large Italian population. We particularly focused on changes in trends following FIT-screening implementation in the target population (50-69 years).

Generalized music therapy to reduce neuroactive drug needs in critically ill patients. Study protocol for a randomized trial.

Background: Critically ill patients are exposed to several physical and emotional stressors, needing analgesic and sedative drugs to tolerate invasive procedures and the harsh intensive care unit (ICU) environment. However, this pharmacological therapy presents several side effects: guidelines suggest using a light sedation target, keeping critically ill patients calm, conscious, and cooperative. Personalized music therapy (MT) can reduce stress and anxiety, decreasing the need for drugs.

IMMUNOREACT 7: Regular aspirin use is associated with immune surveillance activation in colorectal cancer.

Background: Long-term daily use of aspirin reduces incidence and mortality due to colorectal cancer (CRC). This study aimed to analyze the effect of aspirin on the tumor microenvironment, systemic immunity, and on the healthy mucosa surrounding cancer.

Methods: Patients with a diagnosis of CRC operated on from 2015 to 2019 were retrospectively analyzed (METACCRE cohort).

Association between Pancreatoblastoma and Familial Adenomatous Polyposis: Review of the Literature with an Additional Case.

Background: Adult pancreatoblastoma (PBL) is a rare pancreatic malignancy, with recent evidence suggesting a possible link to familial adenomatous polyposis (FAP). This study aims to review the latest evidence and explore a possible association between adult PBL and FAP.

Methods: Two independent literature reviews were conducted: (1) on PBL and FAP, and (2) on PBL in the adult population not diagnosed with FAP.

Agonists of melatonin receptors strongly promote the functional recovery from the neuroparalysis induced by neurotoxic snakes.

Snake envenoming is a major, but neglected, tropical disease. Among venomous snakes, those inducing neurotoxicity such as kraits (Bungarus genus) cause a potentially lethal peripheral neuroparalysis with respiratory deficit in a large number of people each year. In order to prevent the development of a deadly respiratory paralysis, hospitalization with pulmonary ventilation and use of antivenoms are the primary therapies currently employed.

[Management of patients with chronic pain: emerging perspectives and current practices.].

According to the International association for the study of pain (Aisd), chronic pain is «an unpleasant sensory and emotional experience associated with, or resembling, ongoing, or potential tissue damage». The evolution of the definition of chronic pain has recognized the centrality of subjective and multidimensional valence, involving biological, psychological, and social aspects. Hence, there is a need to introduce patient-centered medicine and broaden the chronic pain management modalities.

Multiple colorectal adenomas syndrome: The role of MUTYH mutation and the polyps' number in clinical management and colorectal cancer risk.

Background & Aims: Multiple colorectal adenomas (MCRAs) can result from APC (AFAP) or biallelic MUTYH (MAP) mutations, but most patients are wild type and referred to as non-APC/MUTYH polyposis (NAMP). We aim to examine the risk of colorectal cancer (CRC) and the role of endoscopy in managing patients with MCRAs, with a specific focus on clinical features and genotype.

Methods: Records of MRCAs between 2000 and 2022 were retrospectively analysed.

Genomic Scanning of Inbreeding Depression for Litter Size in Two Varieties of Iberian Pigs.

Inbreeding depression is expected to be more pronounced in fitness-related traits, such as pig litter size. Recent studies have suggested that the genetic determinism of inbreeding depression may be heterogeneous across the genome. Therefore, the objective of this study was to conduct a genomic scan of the whole pig autosomal genome to detect the genomic regions that control inbreeding depression for litter size in two varieties of Iberian pigs (Entrepelado and Retinto).

A multivariate gametic model for the analysis of purebred and crossbred data. An example between two populations of Iberian pigs.

Crossbreeding plays a pivotal role within pig breeding programmes, aiming to maximize heterosis and improve reproductive traits in crossbred maternal lines. Nevertheless, there is evidence indicating that the performance of reciprocal crosses between two genetic lines might exhibit variability. These variations in performance can be attributed to differences in the correlations between gametic effects, acting as either sire or dam, within purebred and crossbred populations.

Erector Spinae Plane Block and Chronic Pain: An Updated Review and Possible Future Directions.

Chronic pain is a common, pervasive, and often disabling medical condition that affects millions of people worldwide. According to the Global Burden of Disease survey, painful chronic conditions are causing the largest numbers of years lived with disability worldwide. In America, more than one in five adults experiences chronic pain.

Fertility specialists' views, behavior, and attitudes towards the use of endometrial scratching in Italy.

Background: Endometrial scratching (ES) or injury is intentional damage to the endometrium performed to improve reproductive outcomes for infertile women desiring pregnancy. Moreover, recent systematic reviews with meta-analyses and randomized controlled trials demonstrated that ES is not effective, data on the safety are limited, and it should not be recommended in clinical practice. The aim of the current study was to assess the view and behavior towards ES among fertility specialists throughout infertility centers in Italy, and the relationship between these views and the attitudes towards the use of ES as an add-on in their commercial setting.

Potential of fluorescent tracers to appraise biochar amendment strategies for pesticide mitigation - insights from comparative sorption.

Mitigation of pesticide dispersion in soil and water is required to protect ecosystem health and the anthropic uses of water bodies. Biochar amendments have been suggested to reduce pesticide dispersion due to their high sorption potentials. Nevertheless, appraisals at different scales have been limited by the costs of pesticide analyses.