Detection of aberrant locomotor activity in a mouse model of lung cancer via home cage monitoring.

Introduction: Lung cancer is the first cause of cancer death in the world, due to a delayed diagnosis and the absence of efficacy therapies. KRAS mutation occurs in 25% of all lung cancers and the concomitant mutations in LKB1 determine aggressive subtypes of these tumors. The improvement of therapeutical options for KRASG12C mutations has increased the possibility of treating these tumors, but resistance to these therapies has emerged.

Computational and digital analyses in the INSPIRE mouse cohort to define sex-specific functional determinants of biological aging.

Biological age, which reflects the physiological state of an individual, offers a better predictive value than chronological age for age-related diseases and mortality. Nonetheless, determining accurate functional features of biological age remains challenging due to the multifactorial nature of aging. Here, we established a unique mouse cohort comprising 1576 male and female outbred SWISS mice subjected or not to high-fat, high-sucrose diet to investigate multiorgan/system biological aging throughout adulthood.

Unraveling the link: locomotor activity exerts a dual role in predicting Achilles tendon healing and boosting regeneration in mice.

Introduction: Tendon disorders present significant challenges in the realm of musculoskeletal diseases, affecting locomotor activity and causing pain. Current treatments often fall short of achieving complete functional recovery of the tendon. It is crucial to explore, in preclinical research, the pathways governing the loss of tissue homeostasis and its regeneration.

Data repurposing from digital home cage monitoring enlightens new perspectives on mouse motor behaviour and reduction principle.

In this longitudinal study we compare between and within-strain variation in the home-cage spatial preference of three widely used and commercially available mice strains-C57BL/6NCrl, BALB/cAnNCrl and CRL:CD1(ICR)-starting from the first hour post cage-change until the next cage-change, for three consecutive intervals, to further profile the circadian home-cage behavioural phenotypes. Cage-change can be a stressful moment in the life of laboratory mice, since animals are disturbed during the sleeping hours and must then rapidly re-adapt to a pristine environment, leading to disruptions in normal motor patterns. The novelty of this study resides in characterizing new strain-specific biological phenomena, such as activity along the cage walls and frontality, using the vast data reserves generated by previous experimental data, thus introducing the potential and exploring the applicability of data repurposing to enhance Reduction principle when running in vivo studies.

Excessive rest time during active phase is reliably detected in a mouse model of myotonic dystrophy type 1 using home cage monitoring.

Myotonic dystrophy type 1 (DM1) is a dominantly inherited neuromuscular disease caused by the abnormal expansion of CTG-repeats in the 3'-untranslated region of the Dystrophia Myotonica Protein Kinase (DMPK) gene, characterized by multisystemic symptoms including muscle weakness, myotonia, cardio-respiratory problems, hypersomnia, cognitive dysfunction and behavioral abnormalities. Sleep-related disturbances are among the most reported symptoms that negatively affect the quality of life of patients and that are present in early and adult-onset forms of the disease. DMSXL mice carry a mutated human transgene containing >1,000 CTGrepeats, modeling an early onset, severe form of DM1.

Antibody gene transfer treatment drastically improves epidermal pathology in a keratitis ichthyosis deafness syndrome model using male mice.

Background: Keratitis ichthyosis deafness (KID) syndrome is a rare disorder caused by hemichannel (HC) activating gain-of-function mutations in the GJB2 gene encoding connexin (Cx) 26, for which there is no cure, or current treatments based upon the mechanism of disease causation.

Methods: We applied Adeno Associated Virus (AAV) mediated mAb gene transfer (AAVmAb) to treat the epidermal features of KID syndrome with a well-characterized HC blocking antibody using male mice of a murine model that replicates the skin pathology of the human disease.

Findings: We demonstrate that in vivo AAVmAb treatment significantly reduced the size and thickness of KID lesions, in addition to blocking activity of mutant HCs in the epidermis in vivo.

Regional hyperthermia with cisplatin added to gemcitabine versus gemcitabine in patients with resected pancreatic ductal adenocarcinoma: The HEAT randomised clinical trial.

Background: Regional hyperthermia (RHT) with cisplatin added to gemcitabine showed efficacy in gemcitabine-pre-treated patients with advanced pancreatic ductal adenocarcinoma. We conducted a randomised clinical trial to investigate RHT with cisplatin added to gemcitabine (GPH) compared with gemcitabine (G) in the adjuvant setting of resected pancreatic ductal adenocarcinoma.

Methods: This randomised, multicentre, open-label trial randomly assigned patients to either GPH (gemcitabine 1000 mg/m on day 1, 15 and cisplatin 25 mg/m with RHT on day 2, 3 and 15,16) or to G (gemcitabine 1000 mg/m on day 1,8,15), four-weekly over six cycles.

Minimally invasive vs. open segmental resection of the splenic flexure for cancer: a nationwide study of the Italian Society of Surgical Oncology-Colorectal Cancer Network (SICO-CNN).

Background: Evidence on the efficacy of minimally invasive (MI) segmental resection of splenic flexure cancer (SFC) is not available, mostly due to the rarity of this tumor. This study aimed to determine the survival outcomes of MI and open treatment, and to investigate whether MI is noninferior to open procedure regarding short-term outcomes.

Methods: This nationwide retrospective cohort study included all consecutive SFC segmental resections performed in 30 referral centers between 2006 and 2016.

A multicentre study on spontaneous in-cage activity and micro-environmental conditions of IVC housed C57BL/6J mice during consecutive cycles of bi-weekly cage-change.

Mice respond to a cage change (CC) with altered activity, disrupted sleep and increased anxiety. A bi-weekly cage change is, therefore, preferred over a shorter CC interval and is currently the prevailing routine for Individually ventilated cages (IVCs). However, the build-up of ammonia (NH3) during this period is a potential threat to the animal health and the literature holds conflicting reports leaving this issue unresolved.

Microglia modulate hippocampal synaptic transmission and sleep duration along the light/dark cycle.

Microglia, the brain's resident macrophages, actively contribute to the homeostasis of cerebral parenchyma by sensing neuronal activity and supporting synaptic remodeling and plasticity. While several studies demonstrated different roles for astrocytes in sleep, the contribution of microglia in the regulation of sleep/wake cycle and in the modulation of synaptic activity in the different day phases has not been deeply investigated. Using light as a zeitgeber cue, we studied the effects of microglial depletion with the colony stimulating factor-1 receptor antagonist PLX5622 on the sleep/wake cycle and on hippocampal synaptic transmission in male mice.

Doxycycline rescues recognition memory and circadian motor rhythmicity but does not prevent terminal disease in fatal familial insomnia mice.

Fatal familial insomnia (FFI) is a dominantly inherited prion disease linked to the D178N mutation in the gene encoding the prion protein (PrP). Symptoms, including insomnia, memory loss and motor abnormalities, appear around 50 years of age, leading to death within two years. No treatment is available.

Modifying food items valuation and weight with gamified executive control training.

Recent lines of research suggest that repeated executive control of motor responses to food items modifies their perceived value and in turn their consumption. Cognitive interventions involving the practice of motor control and attentional tasks have thus been advanced as potential approach to improve eating habits. Yet, their efficacy remains debated, notably due to a lack of proper control for the effects of expectations.

Intranasal Low-Dose Naltrexone Against Opioid Side Effects: A Preclinical Study.

Opioids are broad spectrum analgesics that are an integral part of the therapeutic armamentarium to combat pain in the clinical practice. Unfortunately, together with analgesia, a number of adverse effects can occur such as nausea, vomiting, constipation, gastrointestinal alterations and cognitive impairments. Naltrexone is a competitive antagonist of opioid receptors commonly used to treat opioid addiction; its oral use against agonists side effects is limited by the decrease of opioids-therapeutic efficacy and own adverse effects.

A Non-invasive Digital Biomarker for the Detection of Rest Disturbances in the SOD1G93A Mouse Model of ALS.

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease that affects both central and peripheral nervous system, leading to the degeneration of motor neurons, which eventually results in muscle atrophy, paralysis, and death. Sleep disturbances are common in patients with ALS, leading to even further deteriorated quality of life. Investigating methods to potentially assess sleep and rest disturbances in animal models of ALS is thus of crucial interest.

The critical view of safety during laparoscopic cholecystectomy: Strasberg Yes or No? An Italian Multicentre study.

Background: Laparoscopic cholecystectomy is considered the gold standard for the treatment of gallbladder lithiasis; nevertheless, the incidence of bile duct injuries (BDI) is still high (0.3-0.8%) compared to open cholecystectomy (0.

Ultrasound assisted wet media milling synthesis of nanofiber-cage LiFePO/C.

To meet the objectives of the Intergovernmental Panel on Climate Change nations are adopting policies to encourage consumers to purchase electric vehicles. Electrification of the automobile industry reduces greenhouse gases but active metals for the cathode-LiCoO and LiNiO-are toxic and represent an environmental challenge at the end of their lifetime. LiFePO (LFP) is an attractive alternative that is non-toxic, thermally stable, and durable but with a moderate theoretical capacity and a low electrical conductivity.

Mid-transverse colon cancer and extended versus transverse colectomy: Results of the Italian society of surgical oncology colorectal cancer network (SICO CCN) multicenter collaborative study.

Introduction: Transverse colon cancer (TCC) is poorly studied, and TCC cases are often excluded from large prospective randomized trials because of their complexity and their potentially high complication rate. The best surgical approach for TCC has yet to be established. The aim of this large retrospective multicenter Italian series is to investigate the advantages and disadvantages of both hemicolectomy and transverse colectomy in order to identify the best surgical approach.

Influence of frequency and amplitude on the mucus viscoelasticity of the novel mechano-acoustic Frequencer™.

Background: Cystic fibrosis affects 1/3200 Caucasians. This genetic disease disturbs the ion and water homeostasis across epithelia, thus rendering mucus more viscous and harder to expel. Conventional treatments rely on the clapping method coupled with postural drainage.

Towards large scale automated cage monitoring - Diurnal rhythm and impact of interventions on in-cage activity of C57BL/6J mice recorded 24/7 with a non-disrupting capacitive-based technique.

Background And Aims: Automated recording of laboratory animal's home cage behavior is receiving increasing attention since such non-intruding surveillance will aid in the unbiased understanding of animal cage behavior potentially improving animal experimental reproducibility.

Material And Methods: Here we investigate activity of group held female C57BL/6J mice (mus musculus) housed in standard Individually Ventilated Cages across three test-sites: Consiglio Nazionale delle Ricerche (CNR, Rome, Italy), The Jackson Laboratory (JAX, Bar Harbor, USA) and Karolinska Insititutet (KI, Stockholm, Sweden). Additionally, comparison of female and male C57BL/6J mice was done at KI.

Water treatment: Mn-TiO synthesized by ultrasound with increased aromatics adsorption.

Pharma-products are mostly single or multiple cyclic compounds. They pollute surface water and are persistent in the aquatic ecosystem. When irradiated by UV light, TiO catalysts cleave or degrade organic contaminants in water.

Stereoselective synthesis of hernandulcin, peroxylippidulcine A, lippidulcines A, B and C and taste evaluation.

The first stereoselective synthesis of lippidulcines A, B and C has been accomplished starting from (+)-hernandulcin, which has been prepared on a multigram scale. The previously assigned absolute configurations have been confirmed. The key steps of this synthesis are based on a modified version of the Kornblum-DeLaMare rearrangement, and on a highly regioselective and stereoselective ketone reduction with the MeCBS reagent.

Hypotonic stress-induced calcium signaling in Saccharomyces cerevisiae involves TRP-like transporters on the endoplasmic reticulum membrane.

Saccharomyces cerevisiae cells respond to hypotonic stress (HTS) by a cytosolic calcium rise, either generated by an influx of calcium from extracellular medium, when calcium is available, or by a release from intracellular stores in scarcity of extracellular calcium. Calcium release from intracellular compartments is peculiarly inhibited by external calcium in a calcineurin-independent and Cch1-, but not Mid1-, driven manner. HTS-induced calcium release is also negatively regulated by the ER protein Cls2 and involves a poorly characterized protein, FLC2/YAL053W gene product, previously proposed to be required for FAD transport in the ER, albeit, due to its molecular features, it was also previously classified as an ion transporter.