Advances in Therapeutic Strategies for the Management of Clostridioides difficile Infection.

The infection caused by Clostridioides difficile represents one of the bacterial infections with the greatest increase in incidence among nosocomial infections in recent years. C. difficile is a Gram-positive bacterium able to produce toxins and spores. In some cases, infection results in severe diarrhoea and fulminant colitis, which cause prolonged hospitalisation and can be fatal, with repercussions also in terms of health economics. C. difficile is the most common cause of antibiotic-associated diarrhoea in the healthcare setting. The problem of bacterial forms that are increasingly resistant to common antibiotic treatments is also reflected in C. difficile infection (CDI). One of the causes of CDI is intestinal dysmicrobialism induced by prolonged antibiotic therapy. Moreover, in recent years, the emergence of increasingly virulent strains resistant to antibiotic treatment has made the picture even more complex. Evidence on preventive treatments to avoid recurrence is unclear. Current guidelines indicate the following antibiotics for the treatment of CDI: metronidazole, vancomycin, and fidaxomycin. This short narrative review provides an overview of CDI, antibiotic resistance, and emerging treatments.

Antimicrobial Resistance in Gonorrhea.

Antimicrobial resistance is a global public health emergency. The World Health Organization recently highlighted the growing number of new sexually transmitted infections such as gonorrhea, syphilis, and Chlamydia, which are resistant to common antibiotics. The phenomenon is also on the rise due to increasing intercontinental travel. Emerging antibiotic-resistant strains of gonorrhea are particularly associated with international spread from Southeast Asian travelers. Infection with Neisseria gonorrhoeae can cause a wide spectrum of associated diseases such as dermatitis, arthritis and septic arthritis, and pelvic inflammatory disease, and can even lead to serious health consequences for the individual. Natural infection confers no immunity, and vaccination is not available currently, although in several countries, it has been reported that the antimeningococcal vaccine may protect against gonorrhea. Implementing all necessary preventive measures is crucial, as well as appropriate and timely diagnostic methods and effective antimicrobial therapeutic treatments in the correct modalities to avoid the increase of forms of gonorrhea that are resistant to common antibiotics and difficult to eradicate.

The Impact of Antimicrobial Resistance in Cystic Fibrosis.

The phenomenon of antimicrobial resistance (AMR) is a critical global health challenge, with prospects indicating its potential to become the leading cause of death worldwide in the coming years. Individuals with pre-existing conditions, such as neoplastic disease undergoing chemotherapy, those on immunosuppressive therapy, and individuals with rare diseases like cystic fibrosis (CF), face heightened challenges due to AMR. CF is a rare disease caused by a deficiency in the synthesis of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel protein, resulting in multi-organ clinical symptoms, particularly in the respiratory system. PwCF experience recurrent pulmonary exacerbations triggered by bacterial or viral infections, making them particularly vulnerable to the impact of AMR. This review delves into the complex relationship between AMR and climate dynamics, focusing on the unique challenges faced by individuals with CF. It discusses the methods employed to measure AMR, its global impact on antibiotic resistance, and the specific microbial communities present in the CF airway. The review also explores the intricacies of antimicrobial resistance within the context of cystic fibrosis, emphasizing the urgent need for research in this field.

Therapeutic and Unconventional Strategies to Contrast Antimicrobial Resistance: A Literature Review.

The fast emergence and spread of drug-resistant infectious pathogens and the resulting increase in associated and attributable deaths is a major health challenge globally. Misuse of antibiotics, insufficient infection prevention and control (IPC) in hospitals, food, animal feed, and environmental contamination due to drug-resistant microbes and genes have been the main drivers for antimicrobial resistance (AMR). AMR can lead to ineffective drug treatment, persistence of infection, and risk of severe disease especially in frail, immunocompromised, elderly patients. It is estimated that AMR will cause around 10 million deaths every year after 2050, the same number of deaths due to cancer occurring every year in present times. AMR affects the progress towards the Sustainable Development Goals (SDGs) and is crucial for pandemic preparedness and response. Therefore, the international authorities such as G7 and G20, the World Bank, the World Health Organization (WHO), the General Assembly of the United Nations, and the European Union call for innovative antibiotics and strategies to combat this health threat. To underline this emergency, two lists of resistant "priority pathogens" and a global research agenda for AMR in human health have been published by the WHO. Although investigation of safe and effective treatments remains a top priority, the pipeline for new antimicrobials is not promising, and alternative solutions are needed urgently. In recent times, the interest in fighting AMR has increased, and a number of preventive or therapeutic options have been explored. In this literature review, we discuss the scientific evidence and the limits of the main proven unconventional strategies to combat the AMR phenomenon in the human sector.

What Is the Role of Nutraceutical Products in Cancer Patients? A Systematic Review of Randomized Clinical Trials.

Chemotherapy represents the main pharmacological cancer treatment. Recently, positive effects emerged with the combination of anticancer therapy and nutraceutical products. The aim of this systematic review is to collect and synthesize the available scientific evidence regarding the potential effects of nutraceuticals on cancer cells. A systematic literature search of randomized clinical trials of nutraceutical products in patients with cancer published up to 15 December 2022 was conducted using three data sources: Embase, PubMed, and Web of Science. The effect of high-dose isoflavone supplements on prostate cancer resulted in stabilization or reduction of PSA concentrations in 50% of isoflavone group patients six months after treatment. High doses of vitamin D supplementation plus chemotherapy in patients with advanced or metastatic colorectal cancer showed a median PFS of 13.0 months (95% CI, 10.1-14.7 months) for 49 patients. The effect of vitamin D supplementation on markers of inflammatory level and antioxidant capacity in women with breast cancer showed a significant increase in serum vitamin D concentration (28 ± 2.6 to 39 ± 3.5; p = 0.004) after 8 weeks of treatment. In conclusion, nutraceutical supplements represent a potentially growing sector and can be utilized in medical treatment or nutrition to provide integrated medical care.

Health Effects of Natural Antioxidants.

Free radicals are produced during metabolic processes in the human body and can lead to oxidative stress, cellular aging, and the development of various diseases [...].

An ELISA Test Able to Predict the Development of Oral Cancer: The Significance of the Interplay between Steroid Receptors and the EGF Receptor for Early Diagnosis.

Oral disorders including non-homogeneous leukoplakia, erythroplakia, erosive lichen planus, and many others can potentially progress to oral squamous cell carcinoma (OSCC). Currently, the late diagnosis of OSCC contributes to high mortality rates, emphasizing the need for specific markers and early intervention. In this study, we present a novel, quick, sensitive, and non-invasive method for the early detection and screening of oral cancer, enabling the qualitative assessment of neoplastic forms even before the onset of symptoms. Our method directly examines the expression of oral cancer biomarkers, such as the epithelial growth factor receptor (EGFR), and steroid receptors, including the androgen receptor (AR) and the estrogen receptor (ER). The crosstalk between sexual hormones and the EGF receptor plays a crucial role in the progression of different types of cancers, including head and neck squamous cell carcinoma. To implement our method, we developed a kit box comprising nine wells or stations, each containing buffers, lysis systems, and dried/lyophilized antibodies stored at room temperature. The kit includes instruments for sample collection and a PVDF strip (Immobilon) with specific primary antibodies immobilized on it. These antibodies capture the target proteins from cytological samples. Additionally, complementary tools are provided to ensure efficient utilization and optimal test performance. The technique can be performed outside the laboratory, either "patient side" with an instant chemocolorimetric response or with a digital reader utilizing the enzyme-linked immunosorbent assay (ELISA) method.

Antifungal Drug Resistance: An Emergent Health Threat.

Fungal infections, named mycosis, can cause severe invasive and systemic diseases that can even lead to death. In recent years, epidemiological data have recorded an increase in cases of severe fungal infections, caused mainly by a growing number of immunocompromised patients and the emergence of fungal pathogenic forms that are increasingly resistant to antimycotic drug treatments. Consequently, an increase in the incidence of mortality due to fungal infections has also been observed. Among the most drug-resistant fungal forms are those belonging to the Candida and Aspergillus spp. Some pathogens are widespread globally, while others are endemic in some areas only. In addition, some others may represent a health threat for some specific subpopulations and not for the general public. In contrast to the extensive therapeutic armamentarium available for the antimicrobial chemotherapeutic treatment of bacteria, for fungal infections there are only a few classes of antimycotic drugs on the market, such as polyenes, azoles, echinocandins, and a few molecules are under trial. In this review, we focused on the systemic mycosis, highlighted the antifungal drug compounds available in the pipeline, and analyzed the main molecular mechanisms for the development of antifungal resistance to give a comprehensive overview and increase awareness on this growing health threat.

Advances in Molecular and Translational Medicine.

Translational medicine is an interdisciplinary field that combines basic research findings with clinical practice to accelerate the development of new diagnostic tools, therapies, and preventive strategies for human diseases [...].

Omicron variant evolution on vaccines and monoclonal antibodies.

The severe acute respiratory syndrome coronavirus (SARS-CoV)-2 responsible for the global COVID-19 pandemic has caused almost 760 million confirmed cases and 7 million deaths worldwide, as of end-February 2023. Since the beginning of the first COVID-19 case, several virus variants have emerged: Alpha (B1.1.7), Beta (B135.1), Gamma (P.1), Delta (B.1.617.2) and then Omicron (B.1.1.529) and its sublineages. All variants have diversified in transmissibility, virulence, and pathogenicity. All the newly emerging SARS-CoV-2 variants appear to contain some similar mutations associated with greater "evasiveness" of the virus to immune defences. From early 2022 onward, several Omicron subvariants named BA.1, BA.2, BA.3, BA.4, and BA.5, with comparable mutation forms, have followed. After the wave of contagions caused by Omicron BA.5, a new Indian variant named Centaurus BA.2.75 and its new subvariant BA.2.75.2, a second-generation evolution of the Omicron variant BA.2, have recently been identified. From early evidence, it appears that this new variant has higher affinity for the cell entry receptor ACE-2, making it potentially able to spread very fast. According to the latest studies, the BA.2.75.2 variant may be able to evade more antibodies in the bloodstream generated by vaccination or previous infection, and it may be more resistant to antiviral and monoclonal antibody drug treatments. In this manuscript, the authors highlight and describe the latest evidences and critical issues have emerged on the new SARS-CoV-2 variants.

Comparative study of the anaesthetic efficacy of 4% articaine versus 2% mepivacaine in mandibular third molar germectomy using different anaesthetic techniques: a split-mouth clinical trial.

BACKGROUND: Currently, one of the most discouraging aspects for many patients undergoing dental procedures is the administration of local anaesthesia. Therefore, there is a constant search for new techniques to avoid the invasive and painful nature of the injection. This study aimed to compare the clinical efficacy of local anaesthetics with articaine 4% or mepivacaine 2% (both with epinephrine 1:100.000), using different anaesthetic techniques to perform germectomy of lower third molars and to assess patients' feelings and pain during surgery. METHODS: Totally 50 patients (ranged 11-16 years) who required germectomy of mandibular third molars were recruited. Each patient received local anaesthesia on one side with articaine inoculated with plexus technique while on the other side with mepivacaine using inferior alveolar nerve block technique. The patients' evaluation was performed on pre and intraoperative tactile-pressure feelings and intraoperative pain with four levels on the Visual Analogue Scale (VAS). RESULTS: Surgical operations lasted less with more efficient analgesia when articaine was used. The additional intraosseous injection was required mainly in the mepivacaine group intraoperatively. A few patients had tactile-pressure feelings while intraoperative pain sensation was absent in 90% of cases with articaine. Significant differences were found in the cases who reported "absent" and "moderate" VAS values, favoring the use of articaine. CONCLUSIONS: Articaine injected with a plexus anaesthetic technique seems to be more clinically manageable than mepivacaine for the mandibular third molar germectomy. The discomfort of tactile-pressure feelings and pain experienced was lower using articaine anaesthetic technique used.

Long COVID could become a widespread post-pandemic disease? A debate on the organs most affected.

Long COVID is an emerging problem in the current health care scenario. It is a syndrome with common symptoms of shortness of breath, fatigue, cognitive dysfunction, and other conditions that have a high impact on daily life. They are fluctuating or relapsing states that occur in patients with a history of SARS-CoV-2 infection for at least 2 months. They are usually conditions that at 3 months after onset cannot be explained by an alternative diagnosis. Currently very little is known about this syndrome. A thorough review of the literature highlights that the cause is attributable to deposits of tau protein. Massive phosphorylation of tau protein in response to SARS-CoV-2 infection occurred in brain samples from autopsies of people previously affected with COVID-19. The neurological disorders resulting from this clinical condition are termed tauopathies and can give different pathological symptoms depending on the involved anatomical region of the brain. Peripheral small-fiber neuropathies are also evident among patients with Long COVID leading to fatigue, which is the main symptom of this syndrome. Certainly more research studies could confirm the association between tau protein and Long COVID by defining the main role of tau protein as a biomarker for the diagnosis of this syndrome that is widespread in the post-pandemic period.

What Do We Know About the Smallpox Virus? A Journey Between Clinic and Therapy.

PURPOSE: Modern research is increasingly focusing on the study of new viruses and the re-emergence of past microbes, such as Coronaviruses, particularly Sars-Cov2 that was responsible for the very recent pandemic. METHODS AND RESULTS: This infection manifested itself and still continues to manifest as a severe respiratory syndrome. The main discriminator of whether or not one succeeds in overcoming this infection may depend on a great many factors, but the main one is definitely determined by vaccination, which has minimized hospitalizations and more severe syndromes. CONCLUSION: Recently, a new virus, the monkeypox virus, which was previously confined to Central and West Africa but is now gradually spreading to more than 30 countries including the United States of America, where such an infection is not endemic, is coming forward again.

COVID-19 Pandemic: Therapeutic Strategies and Vaccines.

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), a highly pathogenic and transmissible virus, has spurred an impressive accumulation of knowledge [...].

Salivary microRNA profiling dysregulation in autism spectrum disorder: A pilot study.

Introduction: Autism spectrum disorders (ASD) are the most prevalent neurobiological disorders in children. The etiology comprises genetic, epigenetic, and environmental factors such as dysfunction of the immune system. Epigenetic mechanisms are mainly represented by DNA methylation, histone modifications, and microRNAs (miRNA). The major explored epigenetic mechanism is mediated by miRNAs which target genes known to be involved in ASD pathogenesis. Salivary poly-omic RNA measurements have been associated with ASD and are helpful to differentiate ASD endophenotypes. This study aims to comprehensively examine miRNA expression in children with ASD and to reveal potential biomarkers and possible disease mechanisms so that they can be used to improve faction between individuals by promoting more personalized therapeutic approaches. Materials and methods: Saliva samples were collected from 10 subjects: 5 samples of children with ASD and 5 from healthy controls. miRNAs were analyzed using an Illumina Next-Generation-Sequencing (NGS) system. Results: Preliminary data highlighted the presence of 365 differentially expressed miRNAs. Pathway analysis, molecular function, biological processes, and target genes of 41 dysregulated miRNAs were assessed, of which 20 were upregulated, and 21 were downregulated in children with ASD compared to healthy controls. Conclusion: The results of this study represent preliminary but promising data, as the identified miRNA pathways could represent useful biomarkers for the early non-invasive diagnosis of ASD.

Effects of Vitamin D on the Renin-Angiotensin System and Acute Childhood Pneumonia.

Vitamin D promotes kidney calcium reabsorption and regulates calcium and phosphate metabolism, as well as the intestinal absorption of calcium and phosphorus and bone mineralization events. Vitamin D is also known for its immunomodulatory properties. It has been shown in the literature that the active form of vitamin D, 1,25-dihydroxyvitamin D, performs multiple functions in the adaptive and innate immune system, as well as acting on the endothelial membrane. Recent evidence shows that vitamin D is a negative endocrine modulator of the renin-angiotensin system (RAS), with protection from diseases leading to lung damage, such as pneumonia caused by various pathogens. Vitamin D support associated with the use of antibiotics could be crucial to counteract these infectious diseases.

COVID-19 mRNA Vaccines: A Retrospective Observational Pharmacovigilance Study.

BACKGROUND AND OBJECTIVE: Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus has caused millions of deaths worldwide. The mRNA vaccines prevented the figure from being more severe. The objective of this retrospective study is to evaluate the safety of COVID-19 vaccines by analyzing the adverse events following immunization (AEFIs). METHODS: A retrospective observational pharmacovigilance study was conducted, based on the collection of reports of suspected AEFIs reported between 1 January 2021 and 31 December 2021 at the Naples 3 local health authority. AEFIs were stratified and described according to mRNA vaccine, demographics, clinical status, description of AEFI, and degree of severity. In 2021, local health authority Asl Naples 3 South received 1164 reports of suspected adverse events that occurred following the administration of mRNA vaccines. RESULTS: During the reporting period, 746 reports were related to the Comirnaty vaccine (64.1%), 281 to the Vaxzevria vaccine (24.1%), 107 to the Spikevax vaccine (9.2%), and 30 to the Jcovden vaccine (2.6%); 89.3% of the reports were classified as not serious (N = 1039 reports), the remaining 10.7% as serious (N = 125 reports). CONCLUSIONS: This retrospective pharmacovigilance study demonstrates that COVID-19 mRNA vaccines are safe in all population groups.

Pharmacovigilance is an activity that ensures the safety of health care treatments. The COVID-19 pandemic has accelerated the administration of vaccines whose efficacy and safety is to be evaluated. In the year 2021, an analysis of all reported adverse events following immunization (AEFIs) to the vaccine was conducted on a sample of about 1 million people with the aim of understanding efficacy and safety. All adverse events were divided by age, sex, type of reaction, and severity. Serious reactions were divided into subcategories to report the most common critical issues. At the conclusion of the work, it can be seen that COVID-19 mRNA vaccines are safe but can give serious cardiovascular (12% of the total number of serious reports) and neurological (one serious case that led to the development of Guillain Barré syndrome) side effects that need to be monitored by medical personnel.

Pandemic COVID-19, an update of current status and new therapeutic strategies.

The global COVID-19 pandemic is underway. In recent weeks, several countries throughout the globe, and particularly in Europe, have experienced an exponential increase in the number of individuals infected with COVID-19, probably induced by a new variant of SARS-CoV-2, called the "Omicron variant." Mass vaccination against COVID-19 continues worldwide. Are authorized mRNA vaccines effective against the new Omicron variant? Recently, several pharmaceutical companies have developed oral antiviral pills against SARS-CoV-2, i.e., molnupiravir and paxlovid, that inhibit SARS-CoV-2 viral replication by acting on the RNA polymerase of SARS-CoV. In pre-registration clinical trials, molnupiravir and paxlovid have shown excellent clinical efficacy results, but what impact will these new oral antiviral agents have against pandemic COVID-19? In what specific clinical situations are they preferred over other antivirals such as remdesivir? In this brief review, we explore these important aspects.

Protective Effect of Resveratrol against Hypoxia-Induced Neural Oxidative Stress.

Oxidative stress plays an important role in brain aging and in neurodegenerative diseases. New therapeutic agents are necessary to cross the blood-brain barrier and target disease pathogenesis without causing disagreeable side effects. Resveratrol (RSV) may act as a neuroprotective compound, but little is known about its potential in improving the cognitive and metabolic aspects that are associated with neurodegenerative diseases. The objective of this study was to investigate the protective effects and the underlying mechanisms of RSV against hypoxia-induced oxidative stress in neuronal PC12 cells. For the induction of the hypoxia model, the cells were exposed to oxygen-deprived gas in a hypoxic chamber. Cell cycle and apoptosis were analyzed by a fluorescence activated cell sorting (FACS) analysis. The intracellular reactive oxygen species (ROS) level was analyzed by using dichlorodihydrofluorescein diacetate (DCFDA) and 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA) tests. The expression of activated caspase-3, -9, Bcl-2, Bax, p53, and SOD was investigated by a Western blot analysis. We found that hypoxia reduced PC12 viability by inducing apoptosis, while RSV treatment attenuated the ROS-induced damage by reducing caspase-3, -9, and the Bax/Bcl-2 ratio. The RSV treated groups were found to improve cellular health, with a 7.41% increase in the S phase population in the 10 µM group, compared to the control. Hence, RSV has a protective effect in neuronal cells and may halt the cell cycle in the G1/S phase to repair the intracellular damage. Therefore, RSV could be a good candidate to act as an antioxidant and promising preventive therapeutic agent in neurodegenerative diseases for personalized medicine.

The Role of Curcumin in Prostate Cancer Cells and Derived Spheroids.

A major challenge in the clinical management of prostate cancer (PC) is to inhibit tumor growth and prevent metastatic spreading. In recent years, considerable efforts have been made to discover new compounds useful for PC therapy, and promising advances in this field were reached. Drugs currently used in PC therapy frequently induce resistance and PC progresses toward metastatic castration-resistant forms (mCRPC), making it virtually incurable. Curcumin, a commercially available nutritional supplement, represents an attractive therapeutic agent for mCRPC patients. In the present study, we compared the effects of chemotherapeutic drugs such as docetaxel, paclitaxel, and cisplatin, to curcumin, on two PC cell lines displaying a different metastatic potential: DU145 (moderate metastatic potential) and PC-3 (high metastatic potential). Our results revealed a dose-dependent reduction of DU145 and PC-3 cell viability upon treatment with curcumin similar to chemotherapeutic agents (paclitaxel, cisplatin, and docetaxel). Furthermore, we explored the EGFR-mediated signaling effects on ERK activation in DU145 and PC-3 cells. Our results showed that DU145 and PC-3 cells overexpress EGFR, and the treatment with chemotherapeutic agents or curcumin reduced EGFR expression levels and ERK activation. Finally, chemotherapeutic agents and curcumin reduced the size of DU145 and PC-3 spheroids and have the potential to induce apoptosis and also in Matrigel. In conclusion, despite different studies being carried out to identify the potential synergistic curcumin combinations with chemopreventive/therapeutic efficacy for inhibiting PC growth, the results show the ability of curcumin used alone, or in combinatorial approaches, to impair the size and the viability of PC-derived spheroids.