Gamma-hydroxybutyrate (GHB) for prevention and treatment of alcohol withdrawal

This is the protocol for a review and there is no abstract. The objectives are as follows: To evaluate the efficacy and safety of GHB in prevention and treatment of the AWS, more specifically • to compare the efficacy of GHB with placebo or other drugs; • to identify the most effective GHB dosage and schedules; • to estimate the incidence of side effects; • to carry out a risk-benefit analysis

Evidence-based Recommendations on Periodontal Practice and the Management of Periodontal Patients During and After the COVID-19 Era: Challenging Infectious Diseases Spread by Airborne Transmission

Background: Periodontal care, which was completely suspended during the peak of the SARS-Cov-2 pandemic and was delayed and recurrently discontinued during the succeeding waves, must be safely provided in the COVID-19 era. Objectives: The study aimed to provide recommendations on periodontal practice, optimizing safety, ergonomics, and economic resources, and the management of periodontal patients, ensuring continuity, timing, and effectiveness of periodontal care in the COVID-19 era. Methods: Reported protocols for the dental practice in the context of the COVID-19 and current evidence on periodontitis treatment and prevention were reviewed. Results: Evidence-based recommendations on contamination control and ergonomic improvements for periodontal practice and the management of periodontal patients challenging COVID-19 and airborne infectious diseases have been provided. Conclusion: Due to the economic, ergonomic, and ethical concerns raised by limited periodontal care due to the SARS-Cov-2 pandemic, and awareness of other emerging airborne transmitted infections, the periodontal practice should integrate measures minimizing airborne cross-infections and optimizing time-space and economic resources. The management of periodontal patients in the COVID-19 era should comprise less complex treatments and more comprehensive and definitive approaches, reducing emergencies, session length and number, and, concurrently, extending the recall and maintenance intervals. Moreover, it should implement prevention strategies through teledentistry tools and apps, improving periodontal awareness and self-care, and also through the self-reporting of periodontitis and periodontal risk assessment tools, performing both "population-based" and "high-risk" surveillance of periodontitis. Finally, it should enhance inter-professional collaboration, through telehealth networks, especially targeting subjects at high-risk of both periodontitis and systemic disorders, each of the two variously linked to COVID-19 onset and worsening

Social threat exposure in juvenile mice promotes cocaine-seeking by altering blood clotting and brain vasculature

Childhood maltreatment is associated with increased severity of substance use disorder and frequent relapse to drug use following abstinence. However, the molecular and neurobiological substrates that are engaged during early traumatic events and mediate the greater risk of relapse are poorly understood and knowledge of risk factors is to date extremely limited. In this study, we modeled childhood maltreatment by exposing juvenile mice to a threatening social experience (social stressed, S-S). We showed that S-S experience influenced the propensity to reinstate cocaineseeking after periods of withdrawal in adulthood. By exploring global gene expression in blood leukocytes we found that this behavioral phenotype was associated with greater blood coagulation. In parallel, impairments in brain microvasculature were observed in S-S mice. Furthermore, treatment with an anticoagulant agent during withdrawal abolished the susceptibility to reinstate cocaine-seeking in S-S mice. These findings provide novel insights into a possible molecular mechanism by which childhood maltreatment heightens the risk for relapse in cocaine-dependent individuals

Transcript Regulation of the Recoded Archaeal α-L-Fucosidase In Vivo

Genetic decoding is flexible, due to programmed deviation of the ribosomes from standard translational rules, globally termed “recoding”. In Archaea, recoding has been unequivocally determined only for termination codon readthrough events that regulate the incorporation of the unusual amino acids selenocysteine and pyrrolysine, and for −1 programmed frameshifting that allow the expression of a fully functional α-l-fucosidase in the crenarchaeon Saccharolobus solfataricus, in which several functional interrupted genes have been identified. Increasing evidence suggests that the flexibility of the genetic code decoding could provide an evolutionary advantage in extreme conditions, therefore, the identification and study of interrupted genes in extremophilic Archaea could be important from an astrobiological point of view, providing new information on the origin and evolution of the genetic code and on the limits of life on Earth. In order to shed some light on the mechanism of programmed −1 frameshifting in Archaea, here we report, for the first time, on the analysis of the transcription of this recoded archaeal α-l-fucosidase and of its full-length mutant in different growth conditions in vivo. We found that only the wild type mRNA significantly increased in S. solfataricus after cold shock and in cells grown in minimal medium containing hydrolyzed xyloglucan as carbon source. Our results indicated that the increased level of fucA mRNA cannot be explained by transcript up-regulation alone. A different mechanism related to translation efficiency is discusse

Roles of Tumor-Educated Platelets (TEPs) in the biology of Non-Small Cell Lung Cancer (NSCLC): A systematic review. “Re-discovering the neglected biosources of the liquid biopsy family”

Due to their interactions with the neoplasm, platelets undergo various proteomic and transcriptomic modifications, resulting in the development of what is known as the “Tumor-Educated Platelets (TEPs) phenotype”. Consequently, in addition to their suitability for Liquid Biopsy (LB) applications, they play a pivotal role in the malignancy by communicating with Circulating Tumor Cells (CTCs), Tumor Microenvironment (TME), and the tumor itself through multiple mechanisms and at multiple levels, ultimately promoting the metastasis of cancer. Therefore, this Systematic Review of MEDLINE and the Cochrane Library present in-depth insights into these phenomena, with the aim of enhancing the understanding of the complex interplay between TEPs and Non-Small Cell Lung Cancer (NSCLC). This endeavor serves to provide context and drive medical research efforts, which are increasingly focused on developing novel diagnostic and therapeutic technologies that leverage the specific binding of these platelets to the disease

Navigating the liquid biopsy Minimal Residual Disease (MRD) in non-small cell lung cancer: Making the invisible visible

Liquid biopsy has gained increasing interest in the growing era of precision medicine as minimally invasive technique. Recent findings demonstrated that detecting minimal or molecular residual disease (MRD) in NSCLC is a challenging matter of debate that need multidisciplinary competencies, avoiding the overtreatment risk along with achieving a significant survival improvement. This review aims to provide practical consideration for solving data interpretation questions about MRD in NSCLC thanks to the close cooperation between biologists and oncology clinicians. We discussed with a translational approach the critical point of view from benchside, bedside and bunchside to facilitate the future applicability of liquid biopsy in this setting. Herein, we defined the clinical significance of MRD, focusing on relevant practical consideration about advantages and disadvantages, speculating on future clinical trial design and standardization of MRD technology

Exploring the potential of multiomics liquid biopsy testing in the clinical setting of lung cancer

The transformative role of artificial intelligence (AI) and multiomics could enhance the diagnostic and prognostic capabilities of liquid biopsy (LB) for lung cancer (LC). Despite advances, the transition from tissue biopsies to more sophisticated, non-invasive methods like LB has been impeded by challenges such as the heterogeneity of biomarkers and the low concentration of tumour-related analytes. The advent of multiomics - enabled by deep learning algorithms - offers a solution by allowing the simultaneous analysis of various analytes across multiple biological fluids, presenting a paradigm shift in cancer diagnostics. Through multi-marker, multi-analyte and multi-source approaches, this review showcases how AI and multiomics are identifying clinically valuable biomarker combinations that correlate with patients' health statuses. However, the path towards clinical implementation is fraught with challenges, including study reproducibility and lack of methodological standardization, thus necessitating urgent solutions to solve these common issues.A flow diagram to visualize how multiomics approaches can be split into multi-marker, multi-analyte and multi-source approach; then, their link to AI, to decrypt and use in the clinical setting the messages hidden within them. The combined use of Artificial Intelligence (AI) and multiomics could improve the diagnosis and prognosis of Lung Cancer (LC) via Liquid Biopsy (LB); through multi-marker, multi-analyte, and multi-source analysis, the way is paved for the achievement of these goals, once tested through appropriate large-scale multi-center studies.imag

Family history of cancer as surrogate predictor for immunotherapy with anti-PD1/PD-L1 agents: preliminary report of the FAMI-L1 study.

Aim: Tumors related to hereditary susceptibility seem to have an immunosensitive phenotype. Materials & methods: We conducted a multicenter retrospective study, to investigate if family history of cancer, multiple neoplasms and early onset of cancer could be related to clinical outcomes of anti-PD-1/PD-L1 therapy. Activity and efficacy data of 211 advanced cancer patients (kidney, non-small-cell lung cancer, melanoma, urothelium, colorectal and HeN), treated at seven Italian centers with anti-PD-1/PD-L1 agents, were analyzed. Results: In this preliminary report at multivariate analyses, positive family history of cancer showed a statistically significant relationship with a better objective response rate (p = 0.0024), disease control rate (p = 0.0161), median time to treatment failure (p = 0.0203) and median overall survival (p = 0.0221). Diagnosis of multiple neoplasms significantly correlates only to a better disease control rate, while interestingly non-early onset of cancer and sex (in favor of female patients) showed significant correlation with a better median overall survival (p = 0.0268 and p = 0.0272, respectively). Conclusion: This pilot study seems to individuate easily available patient's features as possible predictive surrogates of clinical benefit for anti-PD-1/PD-L1 treatments. These preliminary results need to be confirmed with a greater sample size, in prospective trials with immunotherapy

Non-Small Cell Lung Cancer Harboring Concurrent EGFR Genomic Alterations: A Systematic Review and Critical Appraisal of the Double Dilemma

The molecular pathways which promote lung cancer cell features have been broadly explored, leading to significant improvement in prognostic and diagnostic strategies. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have dramatically altered the treatment approach for patients with metastatic non-small cell lung cancer (NSCLC). Latest investigations by using next-generation sequencing (NGS) have shown that other oncogenic driver mutations, believed mutually exclusive for decades, could coexist in EGFR-mutated NSCLC patients. However, the exact clinical and pathological role of concomitant genomic aberrations needs to be investigated. In this systematic review, we aimed to summarize the recent data on the oncogenic role of concurrent genomic alterations, by specifically evaluating the characteristics, the pathological significance, and their potential impact on the treatment approach