Pyrosequencing Analysis of O-6-Methylguanine-DNA Methyltransferase Methylation at Different Cut-Offs of Positivity Associated with Treatment Response and Disease-Specific Survival in Isocitrate Dehydrogenase-Wildtype Grade 4 Glioblastoma.

The O-6-methylguanine-DNA methyltransferase (MGMT) gene is a critical guardian of genomic integrity. MGMT methylation in diffuse gliomas serves as an important determinant of patients' prognostic outcomes, more specifically in glioblastomas (GBMs). In GBMs, the absence of MGMT methylation, known as MGMT promoter unmethylation, often translates into a more challenging clinical scenario, tending to present resistance to chemotherapy and a worse prognosis. A pyrosequencing (PSQ) technique was used to analyze MGMT methylation status at different cut-offs (5%, 9%, and 11%) in a sample of 78 patients diagnosed with IDH-wildtype grade 4 GBM. A retrospective analysis was provided to collect clinicopathological and prognostic data. A statistical analysis was used to establish an association between methylation status and treatment response (TR) and disease-specific survival (DSS). The patients with methylated MGMT status experienced progressive disease rates of 84.6%, 80%, and 78.4% at the respective cut-offs of 5%, 9%, and 11%. The number was considerably higher when considering unmethylated patients, as all patients (100%), regardless of the cut-off, presented progressive disease. Regarding disease-specific survival (DSS), the Hazard Ratio (HR) was HR = 0.74 (0.45-1.24; p = 0.251); HR = 0.82 (0.51-1.33; p = 0.425); and HR = 0.79 (0.49-1.29; p = 0.350), respectively. Our study concludes that there is an association between MGMT unmethylation and worse TR and DSS. The 9% cut-off demonstrated a greater potential for patient survival as a function of time, which may shed light on the future need for standardization of MGMT methylation positivity parameters in PSQ.

Investigation of the presence of Non-carious cervical lesions (NCCLs) in ancient adult skulls: analyzing data from prehistoric and historical samples through a systematic review and meta-analysis.

OBJECTIVES: Historically, the prevalence of caries has undergone significant changes, particularly increasing with the industrialization of sugar consumption. When examining ancient populations, lower caries rates are discovered, attributed in part to dietary factors. These populations consumed abrasive foods, leading to occlusal wear and reduced non-axial occlusal forces, potentially influencing Non-Carious Cervical Lesions (NCCLs). Although some attribute NCCLs to abfraction, the mechanism remains debated. This systematic review aims to evaluate the presence of NCCLs in ancient populations, shedding light on the factors contributing to their occurrence. MATERIALS AND METHODS: The present systematic review was registered on PROSPERO, and the manuscript was prepared following PRISMA guidelines. RESULTS: After the literature search and article screening, data from 6 studies were included in the meta-analysis, with only 2 reporting NCCLs in ancient skulls, encopassing 17 subjects in 805 examined skulls, suggesting their presence even before the widespread use of toothbrushes. This finding indicates a potential etiopathogenic mechanism linked to abfraction, but the cause is complex and involves abrasive and erosive factors closely tied to dietary habits. CONCLUSIONS: In summary, NCCLs were present in ancient populations, albeit with a much lower prevalence. Their occurrence cannot be solely attributed to wear mechanisms but must be connected to abrasive factors related to diet or practices with religious and cultural significance, such as the use of labrets. CLINICAL RELEVANCE: Th the knowledge of NCCLs presence in acient sculls is crucial today for better understand the associated risk factors. In this context, the analysis of ancient skulls allows us to discern the role that tooth brushing and diet played in the formation of NCCLs, over the past century.

The Dynamics of OXA-23 ß-Lactamase from Acinetobacter baumannii.

Antibiotic resistance is a pressing topic, which also affects ß-lactam antibiotic molecules. Until a few years ago, it was considered no more than an interesting species from an academic point of view, Acinetobacter baumanii is today one of the most serious threats to public health, so much so that it has been declared one of the species for which the search for new antibiotics, or new ways to avoid its resistance, is an absolute priority according to WHO. Although there are several molecular mechanisms that are responsible for the extreme resistance of A. baumanii to antibiotics, a class D ß-lactamase is the main cause for the clinical concern of this bacterial species. In this work, we analyzed the A. baumanii OXA-23 protein via molecular dynamics. The results obtained show that this protein is able to assume different conformations, especially in some regions around the active site. Part of the OXA-23 protein has considerable conformational motility, while the rest is less mobile. The importance of these observations for understanding the functioning mechanism of the enzyme as well as for designing new effective molecules for the treatment of A. baumanii is discussed.

Comparison of Endodontic Failures between Nonsurgical Retreatment and Endodontic Surgery: Systematic Review and Meta-Analysis with Trial Sequential Analysis.

Background and Objectives: In the presence of a persistent endodontic lesion or endodontic failure, the alternative for the recovery of the dental element is endodontic retreatment or endodontic surgery, which consists in the surgical removal of the root apices with retrograde closure of the endodontium. The objective of this systematic review and meta-analysis was to provide an updated value of the Risk Ratio between the two types of treatment in order to offer to clinicians who propose a non-surgical endodontic retreatment or an endodontic surgery a direct comparison. Materials and Methods: The revision was performed according to PRISMA indications: three databases (PubMed, Scopus and Cochrane register) were consulted through the use of keywords relevant to the revision topic: surgical endodontic retreatment, endodontic retreatment, apicoectomy. This search produced 7568 records which, after eliminating duplicates and applying the inclusion and exclusion criteria, resulted in a total of seven included articles. The meta-analyses were conducted by applying fixed-effects models, given the low percentage of heterogeneity. In addition, trial sequency analysis (TSA) was performed for the analysis of the statistical power of the results and GRADE for the quality of the evidence. Results: The results of the meta-analyses' data report an aggregate risk ratio (RR) between non-surgical endodontic retreatment and surgical endodontic retreatment of: 1.05 [0.74, 1.47] at one year of follow-up; RR 2.22 [1.45, 3.41] at two years of follow-up; an RR 1.08 [0.73 1.62] for a follow-up period of 3-4 years; and an RR 0.92 [0.53, 1.61] for a follow-up period of 8-10 years. Conclusions: The results of the present meta-analysis show that in the long term, the risk of failure is identical for the two groups, and there is only a slightly higher risk of failure for non-surgical endodontic retreatments, when only two years of follow-up are considered.

Optimal Load for Bone Tissue Scaffolds with an Assigned Geometry.

Thanks to the recent advances of three-dimensional printing technologies the design and the fabrication of a large variety of scaffold geometries was made possible. The surgeon has the availability of a wide number of scaffold micro-architectures thus needing adequate guidelines for the choice of the best one to be implanted in a patient-specific anatomic region. We propose a mechanobiology-based optimization algorithm capable of determining, for bone tissue scaffolds with an assigned geometry, the optimal value Lopt of the compression load to which they should be subjected, i.e. the load value for which the formation of the largest amounts of bone is favoured and hence the successful outcome of the scaffold implantation procedure is guaranteed. Scaffolds based on hexahedron unit cells were investigated including pores differently dimensioned and with different shapes such as elliptic or rectangular. The algorithm predicted decreasing values of the optimal load for scaffolds with pores with increasing dimensions. The optimal values predicted for the scaffolds with elliptic pores were found higher than those with rectangular ones. The proposed algorithm can be utilized to properly guide the surgeon in the choice of the best scaffold type/geometry that better satisfies the specific patient requirements.

Polydatin, Natural Precursor of Resveratrol, Promotes Osteogenic Differentiation of Mesenchymal Stem Cells.

Bone loss and fractures are consequences of aging, diseases or traumas. Furthermore the increased number of aged people, due to the rise of life expectancy, needs more strategies to limit the bone loss and regenerate the lost tissue, ameliorating the life quality of patients. A great interest for non-pharmacological therapies based on natural compounds is emerging and focusing on the oligostilbene Polydatin, present in many kinds of fruits and vegetables, when resveratrol particularly in red wines. These molecules have been extensively studied due to their antioxidant and anti-inflammatory effects, showing more recently Resveratrol the ability to enhance osteogenic differentiation and bone formation. However, the clinical applications of Resveratrol are limited due to its low bioavailability and rapid metabolism, while its natural glycosilated precursor Polydatin shows better metabolic stability and major abundance in fresh fruits and vegetables. Nevertheless the role of Polydatin on osteogenic differentiation is still unexplored. Mesenchymal stem cells (MSCs) from dental tissues, such as dental bud stem cells (DBSCs), are able to differentiate toward osteogenic lineage: thus we investigated how Resveratrol and Polydatin influence the differentiation of DBSCs, eventually affecting bone formation. Our results showed that Polydatin increases MSCs osteogenic differentiation sharing similar properties with Resveratrol. These results encourage to deepen the effects of this molecule on bone health and its associated mechanisms of action, wishing for the future a successful use in bone loss prevention and therapy.

Innovative Surgical Management of the Synovial Chondromatosis of Temporo-Mandibular Joints: Highly Conservative Surgical Technique.

Synovial chondromatosis (SC) is an uncommon disease characterized by a benign nodular cartilaginous proliferation arising from the joint synovium, bursae, or tendon sheaths. Although the temporomandibular joint is rarely affected by neoplastic lesions, SC is the most common neoplastic lesion of this joint. The treatment of this disease consists in the extraoral surgery with a wide removal of the lesion; in this study, the authors described a more conservative intraoral surgical approach. Patient with SC of temporomandibular joint typically refer a limitation in the mouth opening, together with a persistent not physiological mandibular protrusion and an appearance of a neoformation located at the right preauricular region: the authors reported 1 scholar patient. After biopsy of the neoformation, confirming the synovial chondromatosis, the patient underwent thus to the surgical excision of the tumor, via authors' conservative transoral approach, to facilitate the enucleation of the neoformation. The mass fully involved the pterygo-maxillary fossa with involvement of the parotid lodge and of the right TMJ: this multifocal extension suggested for a trans-oral surgical procedure, in the light of the suspicion of a possible malignant nature of the neoplasm. Our intraoral conservative approach to surgery is aimed to reduce the presence of unaesthetic scars in preauricular and facial regions, with surgical results undoubtedly comparable to the traditional surgical techniques much more aggressive. Our technique could be a valid, alternative, and safe approach to treat this rare and complex kind of oncological disease.

Isobornyl acrylate: an impurity in alkyl glucosides.

CONTEXT: Alkyl glucosides and alkyl poly-glucosides are widely used as wetting agents, surfactants and emulsifiers in several industrial and cosmetic products. They are known as well-tolerated and are usually added to the primary surfactants in order to reduce the irritating potential of the main foaming agents. OBJECTIVE: Recently, some authors suggested that allergic contact dermatitis to alkyl glucosides might be more frequent than suspected. On the other hand, the chemical structures of glucosides do not show potentially allergenic chemical groups or strongly polarized structures. The aim of our study is to investigate alkyl glucosides carrying out a detailed chemical analysis on samples of raw materials to identify potentially allergenic impurities or by-products contained in commercial samples of alkyl glucosides. MATERIALS AND METHODS: We chemically analyzed samples of cocoyl glucoside, decyl glucoside and lauryl glucoside by three different analytical methods, in order to identify any undesired or polluting substances. RESULT: In each of the three samples, we detected the presence of isobornyl acrylate. Its approximate content in the tested samples is 500 ng/g of the product. DISCUSSION: Isobornyl acrylate is not used in the synthesis of alkyl glucosides, but as a plasticizer in many plastic materials. It can be easily released to materials flowing over these surfaces when they have high extraction power, as glucosides. CONCLUSION: Isobornyl acrylate may play a role as hidden allergen, in the form of an impurity collected during the industrial process, explaining some cases of allergic reaction to alkyl glucosides.

Cytokine gene polymorphisms associate with microbiogical agents in periodontal disease: our experience.

Periodontics has evolved from a simplistic model to a more complex interplay between infection and host response. Genetic factors have been a new addition to the list of risk factors for periodontal diseases. The processes leading to destruction and regeneration of the destroyed tissues are of great interest to both researchers and clinicians. The selective susceptibility of subjects for periodontitis has remained an enigma and wide varieties of risk factors have been implicated for the manifestation and progression of periodontitis. Emerging pathway models suggest that gene-environment interactions are etiologically important in disease pathogenesis. The current practical utility of genetic knowledge in periodontitis is limited. Allelic variants at multiple gene loci probably influence periodontitis susceptibility. The pro-inflammatory cytokine interleukin-1 (IL-1) is a key modulator of host responses to microbial infection and a major modulator of extracellular matrix catabolism and bone resorption, and polymorphisms in the IL-1 gene cluster have been associated with an increased risk of developing severe adult periodontitis. The aim of this study was to test if polymorphisms of genes of IL-1α(+4845) and IL-1ß(+3954) were linked with periodontitis, in a case-control study population, delimited to a specific geographic area, in association with microbiological findings. The polymorphisms observed in IL-1α(+4845) and IL-1ß(+3954) single nucleotide polymorphisms (SNPs), was significantly different among the study groups (healthy controls, mild, moderate and severe periodontitis with p<0.05, d.f.=1. We found a significant correlation between the severe form of periodontitis and the presence of composite genotype (p < 0.05, d.f.=1, calculated among healthy vs. severe). Furthermore a statistically significant association between the presence of bacteria and periodontitis was detected (p<0.05, d.f.=1). In the current investigation findings were concordant with literature observations.

Innovative Alveolar Ridge Preservation Surgical Technique with Immediate Dental Implant Placement: A Retrospective Case Report of 1-Year Follow-Up.

Following tooth extraction, the alveolar ridge undergoes morphological and dimensional changes, including a clot formation that is gradually replaced by granulation tissue. Studies indicate that both horizontal and vertical ridge dimensions decrease after extraction; however, these changes can be mitigated through grafting with biomaterials and barrier membranes. Alveolar ridge preservation (ARP) techniques are employed to counteract bone resorption postextraction, encompassing periosteal inhibition and modified periosteal inhibition (MPI) techniques. The Degidi clot chamber technique offers a means to achieve biomaterial-free extraction sockets, promoting healing and osteointegration. This study aims to present the first rehabilitation of a postextraction dental implant in the maxilla using an innovative ARP procedure via a MPI technique. The technique does not involve autologous or heterologous grafting materials; instead, a cortical lamina and a customized screw are used in conjunction with the blood clot. The primary objective is to protect the vestibular cortical bone from preosteoclastic aggression, which can trigger bone resorption. The technique employs a 0.5-mm cortical lamina to mechanically shield the vestibular cortical bone, preventing vestibular cortical bone resorption and increasing its thickness without the need for biomaterial insertion, relying on the blood clot. The effectiveness of the technique was assessed through a 12-month postimplantation cone-beam computed tomography scan, revealing a 0.5-mm increase. Although based on a single case, the 1-year follow-up results are promising, and further studies are warranted to validate the technique's efficacy.

The literature discusses oral manifestations caused by sexually transmitted viruses: a narrative review.

This review provides practical recommendations for dental practitioners in dealing with oral lesions associated with sexually transmitted diseases (STDs), offering clinically relevant insights to increase the awareness of these diseases in the mainstream of everyday practice. STDs are acquired through unprotected vaginal, anal or oral sex and are caused by more than 30 different types of bacteria, viruses and protozoa. Saliva, precum, semen, vaginal secretions and menstrual blood could be likely vehicles of infections and defensive barriers to infection by pathogenic microbes could be represented via intact mucosal membrane, the diluent function of saliva, and the antimicrobial action of salivary enzymes that collectively contribute to oral health and protection. STD, can directly and indirectly affect mucous membranes, manifesting with characteristic diagnostic signs and lesions. Given their potential oral manifestations, dental professionals need a comprehensive understanding of STD. The findings of this review lay a foundation for comprehending several STDs, emphasizing the importance of physicians as well dental practitioners being open to discussing sexuality issues with patients and providing appropriate therapeutic interventions.

Dietary Polyphenols against Oxidative Stress in Head and Neck Cancer: What's New, What's Next.

Head and neck cancers (HNC) are a worldwide health problem, accounting for over 5% of all types of cancers. Their varied nature makes it sometimes difficult to find clear explanations for the molecular mechanisms that underline their onset and development. While chemio- and radiotherapy are clearly not to be dismissed, we cannot undervalue the effect that polyphenols - especially dietary polyphenols - can have in helping us to cope with this medical emergency. By influencing several different proteins involved in numerous different metabolic pathways, polyphenols can have a broad spectrum of biological action and can hopefully act synergistically to tackle down head and neck cancer. Moreover, being natural molecules, polyphenols does not present any side effects and can even enhance drugs efficacy, making our clinical therapy against head and neck cancer more and more effective. Certainly, oxidative stress plays an important role, altering several molecular pathways, lowering the body's defenses, and ultimately helping to create a microenvironment conducive to the appearance and development of the tumor. In this regard, the regular and constant intake of foods rich in polyphenols can help counteract the onset of oxidative stress, improving the health of the general population. In this review, we highlight the role of polyphenols in managing oxidative stress, with such positive effects that they can be considered new tools to use in our anti-head and neck cancer strategy.

Dentistry in the centuries: a historical overview.

The began of the dentistry as medicine's concept has a long history dating back to 7000 BCE, making it one of the earliest medical specialties. In its early days, dental diseases were often attributed to supernatural causes like "evil spirits" and "tooth worms." However, today, dentistry leverages cutting-edge technologies, including artificial intelligence, for diagnosis and treatment. This journey reflects the remarkable progress made in the field. Despite these advancements, there is still room for improvement in integrating dental knowledge and skills with medical science and engineering backgrounds. Bridging these disciplines could lead to even greater advancements in the diagnosis and maintenance of oral health. Thus, over time, it has transformed from a primitive form of medicine into a modern field that emphasizes preventative dental care, advanced diagnostics, and state-of-the-art treatment.

Possible uses of Hunter-Schreger bands of dental enamel for automated personal identification.

BACKGROUND: Hunter-Schreger bands (HSB) are optical phenomena observed on tooth surfaces under polarized light, resulting from the intersection of enamel prisms. Anthropological studies demonstrate the prevalence of HSB in large mammals, contributing to enamel resistance. Historically, John Hunter and Schreger depicted HSB in dental literature. In dentistry, HSB play a role in non-carious cervical lesions (NCCL) and internal dental perikymata, suggesting their potential for personal identification. Personal identification, crucial in both daily and professional life, involves biometric characteristics, such as fingerprints or facial recognition. The need for non-invasive, rapid, and user-friendly methods has prompted the exploration of using HSB dental images for personal identification. The review aimed to consolidate studies employing HSB for personal identification. METHODS: The scoping review was carried out strictly following the PRISMA-ScR checklist; the search was carried out on tree databases (PubMed, Scopus, Science Direct,) and a register (Cochrane library). RESULTS: The research produced a number of bibliographic sources totaling 410. With the removal of duplicates, 334 were obtained; potentially eligible articles amounted to 14, of which only 4 fully complied with the criteria of eligibility. CONCLUSIONS: From the data in the literature, we can assert that HSB could be used in personal identification, as they are characteristics that are difficult to change and easily detectable.

Factors and management techniques in odontogenic keratocysts: a systematic review.

OBJECTIVES: Odontogenic keratocysts exhibit frequent recurrence, distinctive histopathological traits, a tendency towards aggressive clinical behavior, and a potential linkage to the nevoid basal cell carcinoma syndrome. The aim of this systematic review is to compile insights concerning the control of this condition and assess the effectiveness of various treatment approaches in reducing the likelihood of recurrence. MATERIALS AND METHODS: The following systematic review adhered to the PRISMA guidelines. The systematic revision was registered on PROSPERO and  structured around the questions related to the population, intervention, control, outcome and study design (PICOS). RESULTS: After conducting a search on the PubMed database, we initially identified 944 records. After using end-note software to remove duplicate entries, results totally with 462 distinct records. A thorough review of the titles and abstracts of these articles led to the selection of 50 papers for in-depth examination. Ultimately, following the application of our eligibility criteria, we incorporated 11 articles into our primary outcome analysis. CONCLUSION: Among the studies examined, the most common location for these lesions was found to be in the area of the mandibular ramus and the posterior region of the mandible. In cases where the exact location wasn't specified, the mandible emerged as the predominant site. When we considered the characteristics of these lesions in studies that mentioned locularity, most were described as unilocular in two studies, while in two other studies, the prevalence of multilocular lesions was observed. Risk factors associated with keratocyst recurrence include younger patient age, the presence of multilocular lesions, larger lesion size, and a longer anteroposterior dimension. Certain treatment methods have demonstrated a lack of relapses. These include the use of 5-fluorouracil, marsupialization, enucleation with peripheral ostectomy or resection, enucleation and curettage, as well as resection without creating continuity defects. However, it is important to note that further research is essential. Prospective studies and randomized trials are needed to collect more comprehensive evidence regarding the effectiveness of various treatment approaches and follow-up protocols for managing odontogenic keratocysts. CLINICAL RELEVANCE: Odontogenic keratocysts still enter into differential diagnoses with other lesions that affect the jaw bones such as ameloblastama and other tumor forms, furthermore it is not free from recurrence, therefore the therapeutic approach to the lesion aimed at its elimination can influence both the possible recurrence and complications, knowledge of the surgical methods that offer the most predictable and clinically relevant result for the management of follow-up and recurrences.

Salivary exosomal microRNA profile as biomonitoring tool for diagnosis and prognosis of patients with head and neck squamous cell carcinoma: a systematic review.

OBJECTIVE: Exosomes are extracellular vesicles found in saliva and other body fluids. These vesicles range in size from 30 to 150 nm and play a crucial role in intercellular communication, transporting different biomolecules, actively targeting cells. These vesicles regulate both physiological and pathological processes within recipient cells. MicroRNAs (miRs) are transported within exosomes and are delivered to target cells where they influence signaling pathways, taking on a crucial regulatory role in oncogenesis; for example, they are implicated in progression and infiltration of various cancers, such as head and neck squamous cell carcinoma (HNSCC). MATERIAL AND METHODS: A systematic literature search based on specific keywords, according to the PRISMA guidelines, was carried out on PubMed, Web of Science, Scopus, and Google Scholar. Only original articles were selected during this review. The risk of bias was assessed by QUADAS-2. RESULTS: At the end of the selection process 9 articles were included. In these studies, 41 miRs showed differential expression between healthy subjects and patient with HNSCC. The techniques varied among studies for the extraction and analysis of exosomal miRs. We presented also salivary exosomal miRs pathways, to give insights about pathogenetic mechanisms. CONCLUSIONS: Exosomal microRNA are promising biomarkers for HNSCC detection. MiR-10b-5p, miR-486-5p, miR-24-3p, miR-412-3p, and miR-512-3p are the most promising markers applicable to diagnostics, while miR-1307-5p and miR-519c-3p resulted overexpressed and correlated to worse survival outcomes.

Insights into MLH1 Methylation in Endometrial Adenocarcinoma through Pyrosequencing Analysis: A Retrospective Observational Study.

Background: In cancer care, the MLH1 gene is crucial for DNA mismatch repair (MMR), serving as a vital tumor suppressor. Evaluating MLH1 protein expression status, followed by analysis of MLH1 promoter methylation, has become a key diagnostic and prognostic approach. Our study investigates the complex link between MLH1 methylation and prognosis in endometrial adenocarcinoma (EA) patients. Methodology: MLH1 methylation status was accessed by a Pyrosequencing (PSQ) assay. Qualitative positivity for methylation was established if it exceeded the 11% cut-off; as well, a quantitative methylation analysis was conducted to establish correlations with clinicopathological data, relapse-free survival, and disease-free survival. Results: Our study revealed that 33.3% of patients without MLH1 methylation experienced relapses, surpassing the 23.3% in patients with methylation. Furthermore, 16.7% of patients without methylation succumbed to death, with a slightly higher rate of 17.6% in methylated patients. Qualitative comparisons highlighted that the mean methylation rate in patients experiencing relapse was 35.8%, whereas in those without relapse, it was 42.2%. This pattern persisted in disease-specific survival (DSS), where deceased patients exhibited a higher mean methylation level of 49.1% compared to living patients with 38.8%. Conclusions: Our findings emphasize the efficacy of PSQ for evaluating MLH1 methylation. While unmethylation appears to be associated with a higher relapse rate, the survival rate does not seem to be influenced by methylation. Quantitative percentages suggest that elevated MLH1 methylation is linked to relapse and mortality, though a study with a larger sample size would be essential for statistically significant results.

Oxytocin augmentation and neurotransmitters in prolonged delivery: An experimental appraisal.

The uterus is a highly innervated organ, and during labor, this innervation is at its highest level. Oxytocinergic fibers play an important role in labor and delivery and, in particular, the Lower Uterine Segment, cervix, and fundus are all controlled by motor neurofibers. Oxytocin is a neurohormone that acts on receptors located on the membrane of the smooth cells of the myometrium. During the stages of labor and delivery, its binding causes myofibers to contract, which enables the fundus of the uterus to act as a mediator. The aim of this study was to investigate the presence of oxytocinergic fibers in prolonged and non-prolonged dystocic delivery in a cohort of 90 patients, evaluated during the first and second stages of labor. Myometrial tissue samples were collected and evaluated by electron microscopy, in order to quantify differences in neurofibers concentrations between the investigated and control cohorts of patients. The authors of this experiment showed that the concentration of oxytocinergic fibers differs between non-prolonged and prolonged dystocic delivery. In particular, in prolonged dystocic delivery, compared to non-prolonged dystocic delivery, there is a lower amount of oxytocin fiber. The increase in oxytocin appeared to be ineffective in patients who experienced prolonged dystocic delivery, since the dystocic labor ended as a result of the altered presence of oxytocinergic fibers detected in this group of patients.

The Role of Stakeholders' Understandings in Emerging Antimicrobial Resistance: A One Health Approach.

The increasing misuse of antibiotics in human and veterinary medicine and in agroecosystems and the consequent selective pressure of resistant strains lead to multidrug resistance (AMR), an expanding global phenomenon. Indeed, this phenomenon represents a major public health target with significant clinical implications related to increased morbidity and mortality and prolonged hospital stays. The current presence of microorganisms multi-resistant to antibiotics isolated in patients is a problem because of the additional burden of disease it places on the most fragile patients and the difficulty of finding effective therapies. In recent decades, international organizations like the World Health Organization (WHO) and the European Centre for Disease Prevention and Control (ECDC) have played significant roles in addressing the issue of AMR. The ECDC estimates that in the European Union alone, antibiotic resistance causes 33,000 deaths and approximately 880,000 cases of disability each year. The epidemiological impact of AMR inevitably also has direct economic consequences related not only to the loss of life but also to a reduction in the number of days worked, increased use of healthcare resources for diagnostic procedures and the use of second-line antibiotics when available. In 2015, the WHO, recognising AMR as a complex problem that can only be addressed by coordinated multi-sectoral interventions, promoted the One Health approach that considers human, animal, and environmental health in an integrated manner. In this review, the authors try to address why a collaboration of all stakeholders involved in AMR growth and management is necessary in order to achieve optimal health for people, animals, plants, and the environment, highlighting that AMR is a growing threat to human and animal health, food safety and security, economic prosperity, and ecosystems worldwide.

AI-Aided Search for New HIV-1 Protease Ligands.

The availability of drugs capable of blocking the replication of microorganisms has been one of the greatest triumphs in the history of medicine, but the emergence of an ever-increasing number of resistant strains poses a serious problem for the treatment of infectious diseases. The search for new potential ligands for proteins involved in the life cycle of pathogens is, therefore, an extremely important research field today. In this work, we have considered the HIV-1 protease, one of the main targets for AIDS therapy. Several drugs are used today in clinical practice whose mechanism of action is based on the inhibition of this enzyme, but after years of use, even these molecules are beginning to be interested by resistance phenomena. We used a simple artificial intelligence system for the initial screening of a data set of potential ligands. These results were validated by docking and molecular dynamics, leading to the identification of a potential new ligand of the enzyme which does not belong to any known class of HIV-1 protease inhibitors. The computational protocol used in this work is simple and does not require large computational power. Furthermore, the availability of a large number of structural information on viral proteins and the presence of numerous experimental data on their ligands, with which it is possible to compare the results obtained with computational methods, make this research field the ideal terrain for the application of these new computational techniques.