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The COVID-19 pandemic accelerated research and innovation across numerous fields of medicine. It emphasized how disease concepts must reflect dynamic and heterogeneous interrelationships between physical characteristics, genetics, co-morbidities, environmental exposures, and socioeconomic determinants of health throughout life. This article explores how scientists and other stakeholders must collaborate in novel, interdisciplinary ways at these new frontiers of medicine, focusing on communicable diseases, precision/personalized medicine, systems medicine, and data science. The pandemic highlighted the critical protective role of vaccines against current and emerging threats. Radical efficiency gains in vaccine development (through mRNA technologies, public and private investment, and regulatory measures) must be leveraged in the future together with continued innovation in the area of monoclonal antibodies, novel antimicrobials, and multisectoral, international action against communicable diseases. Inter-individual heterogeneity in the pathophysiology of COVID-19 prompted the development of targeted therapeutics. Beyond COVID-19, medicine will become increasingly personalized via advanced omics-based technologies and systems biology—for example targeting the role of the gut microbiome and specific mechanisms underlying immunoinflammatory diseases and genetic conditions. Modeling proved critical to strengthening risk assessment and supporting COVID-19 decision-making. Advanced computational analytics and artificial intelligence (AI) may help integrate epidemic modeling, clinical features, genomics, immune factors, microbiome data, and other anthropometric measures into a “systems medicine” approach. The pandemic also accelerated digital medicine, giving telehealth and digital therapeutics critical roles in health system resilience and patient care. New research methods employed during COVID-19, including decentralized trials, could benefit evidence generation and decision-making more widely. In conclusion, the future of medicine will be shaped by interdisciplinary multistakeholder collaborations that address complex molecular, clinical, and social interrelationships, fostering precision medicine while improving public health. Open science, innovative partnerships, and patient-centricity will be key to success.

For decades, lead-acid batteries have been supplying power to electrical systems through redox reactions involving Pb and PbO2. However, the energy supply capacity is inherently constrained by low energy density and challenges associated with charge/discharge cycles. Studies have indicated that additions of C to the composition of the active mass improve the electrochemical properties of batteries. This work aims to produce, characterize the microstructure and evaluate the electrochemical properties of Pb-Carbon composites, comparing different types of C (graphite, graphene and xerogel). The samples were produced through powder metallurgy, pressed at 550 MPa and sintered at 320°C-48 h. The microstructure was characterized by XRD, SEM/EDS, and Vickers microhardness. Electrochemical analyses were evaluated through OCP, polarization, and cyclic voltammetry (CV) measurements in a solution of 4.91 mol•L-1 of H2SO4. Microstructural characterizations revealed dispersions of C particles in the Pb matrix and an increase in the microhardness of the composites. Electrochemical analyses showed an increase in polarization resistance and a reduction in the corrosion rate compared to Pb. CV curves, demonstrated that C particles enhanced electrical conductivity for the formation of PbSO4 and PbO2, allowing greater absorption of electrical overpotentials when compared to Pb, thereby improving charge/discharge cycles in positive grids.

3D trench silicon pixel sensors, recently developed by the TimeSPOT collaboration, have shown excellent performance in terms of spatial resolution, timing precision and detection efficiency. The combination of these three features make them one of the best candidate for inner tracking detectors operating in high luminosity hadron colliders experiments. This article presents systematic characterisations of these devices made with minimum ionising particles on irradiated sensors with neutrons up to 2.5 ⋅ 1016 1 MeV neq cm−2. The results show that 3D trench pixels have extremely high resistance to radiation. The measured time resolution and the detection efficiency of irradiated sensors match those of non-irradiated ones if a slightly higher bias voltage, few tens of Volts, is applied to the pixels. As of today, 3D trench pixels are the only sensors capable of achieving 10 ps time resolution after being irradiated at extremely high fluences, extending by far the capabilities of future tracking systems of HEP experiments operating under extreme conditions.

This paper tries to summarize the results of studies from different areas of knowledge supporting the idea that temperamental traits, such as “reckless/hyper-exploratory” attitudes, commonly believed to be associated with psychopathology, surprisingly turn out as adaptive under specific stress conditions. In particular, this paper analyzes an ethologic line of research on primates suggesting models for a sociobiological interpretation of mood disorders in humans; a study that found high frequencies of a genetic variance associated with bipolar disorder in people without bipolar disorder but with hyperactivity/novelty-seeking traits; the outcomes of socio-anthropological-historical surveys on the evolution of mood disorders in Western countries in the last centuries; surveys on changing societies in Africa and African migrants in Sardinia; and studies that found higher frequencies of mania and subthreshold mania among Sardinian immigrants in Latin American megacities. Although it is not unequivocally accepted that the prevalence of mood disorders has increased, it would be logical to suppose that a nonadaptive condition should have disappeared over time; mood disorders, on the contrary, persist and their prevalence might have even increased. This new interpretation could lead to counter discrimination and stigma towards people suffering from the disorder and would be a central point in psychosocial treatments in addition to pharmacological therapy. Our aim is to hypothesize that bipolar disorder, strongly characterized by these traits, may be the result of the interaction between genetic characteristics, not necessarily pathological, and specific environmental conditions rather than a mere product of an aberrant genetic profile. If mood disorders were mere nonadaptive conditions, they would have disappeared over time; however, their prevalence paradoxically persists if not even increases over time. The hypothesis that bipolar disorder may result from the interaction between genetic characteristics, not necessarily pathological, and specific environmental factors seems more credible than considering bipolar disorder as a mere product of an aberrant genetic profile.

Glaucoma is one of the world’s leading causes of blindness, and its management is challenging. The main objective is to lower intraocular pressure through medical, para-surgical, and surgical therapy. Medical therapy often represents the first line of treatment. Although effective in many cases, the eye drops are accompanied by significant problems. They require high patient compliance and can be associated with various side effects, limiting their efficacy. Consequently, the research for new drug delivery systems trying to overcome these limitations is ongoing: numerous devices are developing and gradually entering clinical practice. These new therapeutic options may offer better control of the intraocular pressure, with fewer side effects, and are less dependent on patients’ compliance. Hence, the research in this field continues to flourish. This review summarizes the most recent findings in the scientific literature, underlines the role and possible limitations of the new glaucoma drug delivery systems in clinical practice, and recognizes their new horizons and perspectives.

Introduction: Impairments in social cognition and cognitive deficits in bipolar disorder (BD) offer insights into the disorder’s progression. Understanding how interventions impact both cognitive and emotional aspects of social cognition is essential. This study examines the effects of virtual reality (VR) cognitive remediation on cognitive skills, stratified by age, in the early stages of the disorder. Methods: A secondary analysis of a randomized controlled trial (RCT) compared the efficacy of VR cognitive remediation on cognitive skills between young adults (≤58 years) and older adults (≥59 years) in the experimental group with BD. Results: The experimental group included 39 participants: 24 ≤ 58 years and 15 ≥ 59 years. Young adults showed greater improvement in the Digit Span Backward (0.37 ± 0.35 vs. 0.07 ± 0.26, F = 9.882, p = 0.020) and Digit Symbol tests (3.84 ± 3.05 vs. 1.16 ± 3.8, F = 5.895, p = 0.020). Older adults improved more in the Frontal Assessment Battery (1.00 ± 0.95 vs. 0.54 ± 0.21, F = 5.295, p = 0.027), Matrix test (0.58 ± 0.35 vs. 0.37 ± 0.26, F = 4.606, p = 0.038), and Test of Tale (0.81 ± 0.36 vs. 0.42 ± 0.38, F = 10.115, p = 0.003). Conclusions: Young adults improved more in complex cognitive tasks, while older adults showed better results in simpler tasks. The effectiveness of VR may be due to hyperstimulation of mirror neurons. Further studies are needed to confirm these findings.

Background: Selective deprivation of glutamine has been shown to accelerate the generation of reactive oxygen species (ROS) and to impair the activity of a specific pentose phosphate pathway (PPP) located within the endoplasmic reticulum (ER). The consequent oxidative damage suggests that glucose flux through this reticular pathway might contribute to the redox stress of breast cancer cells. We thus evaluated whether this response is reproduced when the glutamine shortage is coupled with the glucose deprivation. Methods: Cancer growth, metabolic plasticity and redox status were evaluated under saturating conditions and after 48 h starvation (glucose 2.5 mM, glutamine 0.5 mM). The Seahorse technology was used to estimate adenosine triphosphate (ATP)-linked and ATP-independent oxygen consumption rate (OCR) as well as proton efflux rate (PER). 18F-fluoro-deoxy-glucose (FDG) uptake was evaluated through the LigandTracer device. Proliferation rate was estimated by the carboxyfluorescein-diacetate-succinimidyl ester (CFSE) staining, while cell viability by the propidium iodide exclusion assay. Results: Starvation reduced the proliferation rate of MCF-7 cells without affecting their viability. It also decreased lactate release and PER. Overall OCR was left unchanged although ATP-synthase dependent fraction was increased under nutrient shortage. Glutaminolysis inhibition selectively impaired the ATP-independent and the oligomycin-sensitive OCR in control and starved cultures, respectively. The combined nutrient shortage decreased the cytosolic and mitochondrial markers of redox stress. It also left unchanged the expression of the reticular unfolded protein marker GRP78. By contrast, starvation decreased the expression of hexose-6P-dehydrogenase (H6PD) thus decreasing the glucose flux through the ER-PPP as documented by the profound impairment in the uptake rate of FDG. Conclusions: When combined with glucose deprivation, glutamine shortage does not elicit the expected enhancement of ROS generation in the studied breast cancer cell line. Combined with the decreased activity of ER-PPP, this observation suggests that glutamine interferes with the reticular glucose metabolism to regulate the cell redox balance.

Background and Objectives: Aberrant upregulation of fatty acid synthase (FASN), catalyzing de novo synthesis of fatty acids, occurs in various tumor types, including human hepatocellular carcinoma (HCC). Although FASN oncogenic activity seems to reside in its pro-lipogenic function, cumulating evidence suggests that FASN’s tumor-supporting role might also be metabolic-independent. Materials and Methods: In the present study, we show that FASN inactivation by specific small interfering RNA (siRNA) promoted the downregulation of the S-phase kinase associated-protein kinase 2 (SKP2) and the consequent induction of p27KIP1 in HCC cell lines. Results: Expression levels of FASN and SKP2 directly correlated in human HCC specimens and predicted a dismal outcome. In addition, forced overexpression of SKP2 rendered HCC cells resistant to the treatment with the FASN inhibitor C75. Furthermore, FASN deletion was paralleled by SKP2 downregulation and p27KIP1 induction in the AKT-driven HCC preclinical mouse model. Moreover, forced overexpression of an SKP2 dominant negative form or a p27KIP1 non-phosphorylatable (p27KIP1-T187A) construct completely abolished AKT-dependent hepatocarcinogenesis in vitro and in vivo. Conclusions: In conclusion, the present data indicate that SKP2 is a critical downstream effector of FASN and AKT-dependent hepatocarcinogenesis in liver cancer, envisaging the possibility of effectively targeting FASN-positive liver tumors with SKP2 inhibitors or p27KIP1 activators.