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Objectives Sirtuins comprise seven family elements (SIRT1-7) involved in various cell signalling pathways comprising cancer inhibition and tumorigenesis. The present study aims to evaluate SIRT2 and SIRT3 gene expression and potential redox reactions in patients with multiple myeloma (MM) at onset and its correlation with disease status, extent and presence of organ damage secondary to myeloma. Design & Methods Total RNA was extracted from 17 MM patients and 10 controls to assess gene expression using real-time PCR. The NAD+/NADH ratio as well as the levels of glutathione peroxidase (GPx) and hydrogen peroxide (HP) in peripheral blood mononuclear cells (PBMCs) were determined using established biochemical assays. Results SIRT2 and SIRT3 expression is reduced in MM patients compared to healthy controls. Correlational analysis demonstrated that SIRT2 reduction is associated with advanced clinical stage and with more advanced bone lesions than in the remaining patients. SIRT3 expression is correlated with lytic bone lesions. Biochemical analysis indicated an imbalance of oxidative stress biomarkers with low concentrations of the antioxidant enzyme GPx, low amounts of NAD + and higher concentrations of pro-oxidant enzyme HP in PBMCs of MM patients compared to controls. Moreover, MM patients with bone lesions had lower concentrations of NAD + and GPx in PBMCs than patients without signs of bone disease. In addition, MM patients had higher quantities of intracellular HP than controls. Conclusions Our results demonstrate that SIRT2 and SIRT3 are downregulated in MM and that lower concentrations correlate with an advanced stage of disease and redox imbalance. We conclude that SIRT2 and SIRT3 together with oxidative stress biomarkers, may be useful for improved risk stratification of MM patients.

INTRODUCTION: All WHO regions have set measles elimination objective for 2020. To address the specific needs of achieving measles elimination, Nigeria is using a strategy focusing on improving vaccination coverage with the first routine dose of (monovalent) measles (MCV1) at 9 months, providing measles vaccine through supplemental immunization activities (children 9-59 months), and intensified measles case-based surveillance system.METHODS: We reviewed measles immunization coverage from population-based surveys conducted in 2010, 2013 and 2017-18. Additionally, we analyzed measles case-based surveillance reports from 2008-2018 to determine annual, regional and age-specific incidence rates.FINDINGS: Survey results indicated low MCV1 coverage (54.0% in 2018); with lower coverage in the North (mean 45.5%). Of the 153,097 confirmed cases reported over the studied period, 85.5% (130,871) were from the North. Moreover, 70.8% (108,310) of the confirmed cases were unvaccinated. Annual measles incidence varied from a high of 320.39 per 1,000,000 population in 2013 to a low of 9.80 per 1,000,000 in 2009. The incidence rate is higher among the 9-11 months (524.0 per million) and 12-59 months (376.0 per million). Between 2008 and 2018, the incidence rate had showed geographical variation, with higher incidence in the North (70.6 per million) compare to the South (17.8 per million).CONCLUSION: The aim of this study was to provide a descriptive analysis of measles vaccine coverage and incidence in Nigeria from 2008 to 2018 to assess country progress towards measles elimination. Although the total numbers of confirmed measles cases had decreased over the time period, measles routine coverage remains sub-optimal, and the incidence rates are critically high. The high burden of measles in the North highlight the need for region-specific interventions. The measles program relies heavily on polio resources. As the polio program winds down, strong commitments will be required to achieve elimination goals.

Background The global polio eradication initiative has made giant stride by achieving a 99% reduction in Wild poliovirus (WPV) cases, with Nigeria on the verge of being declared polio-free following over 36 months without a WPV. The initiative has provided multiple resources, assets and lessons learnt that could be transitioned to other public health challenges, including improving the quality and vaccination coverage of measles campaigns in order to reduce the incidences of measles in Nigeria. We documented the polio legacy and assets used to support the national measles campaign in 2017/2018. Methods We documented the integration of the measles campaign coordination with the Polio Emergency Operation Centre (EOC) at national and state levels for planning and implementing the measles SIA. Specific polio strategies and assets, such as the EOC incident command framework and facilities, human resource surge capacity, polio GIS resource These strategies were adapted and adopted for the MVC implementation overcome challenges and improve vaccination coverage. We evaluated the performance through a set process and outcome indicators. Results All the 36 states and Federal Capital Territory used the structure and resources in Nigeria and provided counterpart financing for the MVC 2017/ 2018. The 11 polio high-risk states deployed the use of GIS for microplanning process, while daily call-in data were tracked in 99.7% of the LGAs and 70,846 reports were submitted real-time by supervisors using Open data kit (ODK). The national coverage achieved was 87.5% by the post-campaign survey with 65% of states reporting higher coverage in 2018 compared to 2015. Conclusion Polio eradication assets and lessons learned can be applied to measles elimination efforts as the eradication and elimination efforts have similar strategies and programme implementation infrastructure needs. Leveraging these strategies and resources to support MVC planning and implementation resulted in more realistic planning, improved accountability and availability of human and fiscal resources. This approach may have resulted in better MVC outcomes and contributed to Nigeria’s efforts in measles control and elimination.

Introduction Globally, supplemental immunization activities (SIAs) are known to be a major strategy for attainment of the global measles elimination goal of less than one measles case per million population within a geographic area by the year 2020. Adequate planning is critical to the success of a vaccination campaign. To achieve a quality SIA implementation for effective interruption of measles transmission, the World Health Organization introduced the SIA Readiness Assessment Tool, which includes the readiness dashboard. It is a strategic planning tool used to ensure critical activities are completed before SIAs. Nigeria implemented a phased measles SIA in 2017/2018 and used the readiness assessment tool in the planning for the campaign. In this article, we report the use of the readiness assessment dashboard in the 2017/2018 measles SIA, we also reviewed its contributions to the outcome of the campaign looking at the post campaign coverage survey results for the states. Methods We conducted a retrospective review of the readiness assessment dashboard used during the 2017/2018 measles vaccination campaign in Nigeria. The readiness dashboard tool was designed using Microsoft Excel 2016. We reported results in frequencies and proportions using charts and tables. Results The states with 100% readiness a week prior to the campaign scored a post campaign coverage survey result of 84.6 – 96.5% with just one out of the eight states in this category getting a score below 90%. In the same vein, of the eight states that their readiness score at one week to the campaign was below 85%, six had post campaign coverage survey score of less than 90% with the highest score in this category being 92.3%. Some states with good readiness scores also had poor post campaign coverage survey which has been attributed to other factors other than readiness. Conclusion The readiness assessment dashboard for the measles vaccination campaign provided a platform for tracking states readiness. It is our view that a link between readiness assessment and coverage should be examined in future studies.

Conflict has a negative effect on immunization outcomes leading to epidemics of measles and other vaccine preventable diseases. Borno state, located in the North-Eastern parts of the country, started experiencing insurgency since 2009 by a militant group commonly referred to as "Boko Haram", leading to displacement of numerous persons from their homes. The state government created internally displaced persons (IDPs) camps with an estimated 600,000 persons and over 100,000 children aged 9 - 59 months. We explored the challenges in implementing the measles campaign in 2017 and its effect on measles elimination and control efforts in Borno State. METHODS We conducted a retrospective review of the measles surveillance data from the Integrated disease surveillance and response (IDSR), the early warning alert and response system (EWARS), Measles SIA implementation strategy reports and the Post campaign evaluation survey data. RESULT Seven (26%) of the 27 LGAs had security challenges in Borno state in November 2017. Following the measles campaign, 30 EAs were surveyed as part of the post campaign evaluation with a coverage validation of 72%, the lowest reported state level coverage in the country. Reported measles cases in the age cohort

Background As global effort is made towards measles elimination, the use of innovative technology to enhance planning for the campaign has become critical. GIS technology has been applied to track polio vaccination activities in Nigeria with encouraging outcomes. Despite numerous measles vaccination campaigns after the first catch up campaign in 2005, sub-optimal outcomes of previous measles supplemental immunization activities necessitated the use of innovative ideas to achieve better outcomes especially when planning for the 2017/2018 measles vaccination campaign. This led to the application of the use of the GIS technology for the Northern states in 2017/2018 campaign. This study is a report of what was achieved with the use of the GIS in the 2017/2018 measles vaccination campaign in Nigeria. Methods GIS generated ward maps were used for the microplanning processes for the 2017/2018 measles vaccination campaign. These ward maps had estimates of the target population by settlements, the number and location of vaccination posts ensuring that a vaccination post is sited within one-kilometer radius of a settlement, and the number of teams needed to support the vaccination campaign as well as the catchment area and daily implementation plans. The ward microplans were verified by checking for accuracy and consistency of the target population, settlements, number of teams, vaccination posts and daily implementation work plans using a standard checklist. The ward maps were deployed into use for the measles vaccination campaign after the state team driven validation and verification by the National team (Government and Partners) Results The Northern states that applied the GIS technology had a closer operational target population to that on the verified microplan than those of the non-GIS technology states. Greater than 90% of the ward maps had all that is expected in the maps - i.e settlements, target populations, and vaccination posts captured, except Kaduna, Katsina and Adamawa states. Of all enumeration areas sampled during the post-campaign survey in states with GIS ward maps, none had a zero-vaccination coverage of the surveyed children, with the exception of one in Borno state that had security issues. In the post campaign coverage survey, the percentage of responses that gave vaccination post being too far as a reason for non-vaccination of children in the Northern zones that used GIS generated ward maps was less than half the rate seen in the southern zones where the GIS microplanning was not used. Conclusion The use of GIS-generated wards maps improved the quality of ward micro plans and optimized the placement of vaccination posts, resulting in a significant reduction in zero-dose clusters found during the post campaign coverage survey.

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at post-transcriptional level, having a role in many biological processes, such as control of cell proliferation, cell cycle, and cell death. Altered miRNA expression has been reported in many neoplasms, including pituitary adenomas (PAs). PURPOSE: In this study, we aimed to evaluate the expression of 20 miRNAs involved in pathways relevant to pituitary pathophysiology, in PAs and normal pituitary tissue and to correlate their expression profile with clinical and pathological features. METHODS: Pituitary tumor samples were obtained during transphenoidal surgery from patients with non-functioning (NFPA, n = 12) and functioning (n = 11, 5 GH-, 3 ACTH-, 3 PRL-omas) PAs. The expression of selected miRNAs in PAs and in normal pituitary was analyzed by RT-qPCR. miRNAs expression was correlated with demographic, clinical, and neuroradiological data and with histopathological features including pituitary hormones immunostaining, Ki-67 proliferation index, and p53 immunohistochemistry evaluation. RESULTS: All evaluated miRNAs except miR-711 were expressed in both normal and tumor pituitary tissue. Seventeen miRNAs were significantly down-regulated in pituitary tumors compared to normal pituitary. miRNAs were differentially expressed in functioning PAs or in NFPAs, as in the latter group miR-149-3p (p = 0.036), miR-130a-3p (p = 0.014), and miR-370-3p (p = 0.026) were significantly under expressed as compared to functioning tumors. Point-biserial correlation analysis demonstrated a negative correlation between miR-26b-5p and Ki-67 (p = 0.031) and between miR-30a-5p and 'atypical' morphological features (p = 0.038) or cavernous sinus invasion (p = 0.049), while 508-5p was inversely correlated with clinical aggressiveness (p = 0.043). CONCLUSIONS: In this study, we found a significant down-regulation of 17 miRNAs in PAs vs normal pituitary, with differential expression profile related to functional status and tumor aggressiveness.

“Epulis” is a widely used term to describe a localized gingival enlargement. However, a wide range of neoformations might present as localized, slow-growing, asymptomatic gingival masses. A systematic review was conducted to outline the pathological entities that were provisionally dignosed as “epulis” and whose final diagnosis was made after microscopic examination. An electronic search of PubMed, Google Scholar and Scopus databases from January 2000 to February 2021 was performed. An initial search of the databases identified a total of 864 documents, and after a careful process of screening and selection, 14 studies were included in this systematic review and processed for data extraction. The results show that histological examination, sometimes combined with immunohistochemistry, might reveal a wide spectrum of lesions, including hamartomatous lesions, non-neoplastic lesions, benign and malign neoplasms and metastases from distant cancers.

Background The aim of this Italian multicenter study was to evaluate the diagnostic performance of a minimally invasive method for the detection of oral squamous cell carcinoma (OSCC) based on 13-gene DNA methylation analysis in oral brushing samples. Methods Oral brushing specimens were collected in 11 oral medicine centers across Italy. Twenty brushing specimens were collected by each center, 10 from patients with OSCC, and 10 from healthy volunteers. DNA methylation analysis was performed in blindness, and each sample was determined as positive or negative based on a predefined cutoff value. Results DNA amplification failed in 4 of 220 (1.8%) samples. Of the specimens derived from patients with OSCC, 93.6% (103/110) were detected as positive, and 84.9% (90/106) of the samples from healthy volunteers were negative. Conclusion These data confirmed the diagnostic performance of our novel procedure in a large cohort of brushing specimens collected from 11 different centers and analyzed in blindness.

Catfish are important fishery resources in the Niger Delta therefore they require studies on its growth patterns and morphometrics. This study examined the relationship between the length and width of catfish otoliths and their fish length. Catfish samples were harvested from New Calabar and Ase Rivers, Niger Delta, Nigeria, by fishers using cast net and purse seines. The fishes were identified, measured, otoliths removed and measured using standard methods. Simple linear regressions expressed the relationship between otolith dimensions and fish length. A total of 80 individuals made up of 7 species from 5 families (Ariidae, Claroteidae, Claridae, Schilbeidae and Mochokidae) were selected for this study. Correlation analysis between the morphometric parameters of the otoliths from the catfish species in the study area revealed a strong positive correlation between the total length of the fish and the length of the otoliths, with R2 values ranging from 0.86 to 0.98. There was also a strong positive correlation between total fish length and otolith width. The relationship between otolith length and width with the fish length in this study showed curvilinearity, indicating the usefulness of the otolith proportions in back calculation of the length of the fish in biological and paleontological studies.

Objective The aim of this systematic review was to evaluate the complications and side effects associated with the clinical use of orthodontic miniscrews by systematically reviewing the best available evidence. Methods A survey of articles published up to March 2020 investigating the complications associated with miniscrew insertion, in both the maxilla and mandible, was performed using 7 electronic databases. Clinical studies, case reports, and case series reporting complications associated with the use of orthodontic miniscrew implants were included. Two authors independently performed study selection, data extraction, and risk-of-bias assessment. Results The database survey yielded 24 articles. The risk-of-bias assessment revealed low methodological quality for the included studies. The most frequent adverse event reported was root injury with an associated periradicular lesion, vitality loss, pink discoloration of the tooth, and transitory loss of pulp sensitivity. Chronic inflammation of the soft tissue surrounding the miniscrew with mucosal overgrowth was also reported. The other adverse events reported were lesion of the buccal mucosa at the insertion site, soft-tissue necrosis, and perforation of the floor of the nasal cavity and maxillary sinus. Adverse events were also reported after miniscrew removal and included secondary bleeding, miniscrew fracture, scars, and exostosis. Conclusions These findings highlight the need for clinicians to preliminarily assess generic and specific insertion site complications and side effects.

Clinical treatment outcome of MRONJ (medication-related osteonecrosis of the jaw) surgery despite radical osseous removal and primary closure healing still shows differences in terms of outcome and disease recurrence. The study aims to assess the rate of angiogenesis of MRONJ lesions in order to understand the impact of angiogenesis and neoangiogenesis status on MRONJ surgical treatment outcome. This is the first study correlating microvessel density with prognosis in MRONJ surgically-treated patients. The immunohistochemical expression of CD34 and CD105 in MRONJ specimens obtained from surgically-treated patients was evaluated. The most vascularized areas detected by CD34 and CD105 were selected and the microvessel density value of the samples was registered. Samples were retrospectively divided according to the clinical outcome of MRONJ surgical treatment, dividing patients into two groups, “healed” and “not healed”. Statistical analysis was performed to assess if neovessels could influence treatment outcome in patients undergoing radical surgery. In the examined cohort, this value was highly predictive of better treatment outcome after radical surgery of MRONJ. Understanding of angiogenesis-dependent factors deserves further attention as a future target for MRONJ prevention and therapies.

The Medication-Related Osteonecrosis of Jaws (MRONJ) diagnosis process and its prevention play a role of great and rising importance, not only on the Quality of Life (QoL) of patients, but also on the decision-making process by the majority of dentists and oral surgeons involved in MRONJ prevention (primary and secondary). The present paper reports the update of the conclusions from the Consensus Conference—held at the Symposium of the Italian Society of Oral Pathology and Medicine (SIPMO) (20 October 2018, Ancona, Italy)—after the newest recommendations (2020) on MRONJ were published by two scientific societies (Italian Societies of Maxillofacial Surgery and Oral Pathology and Medicine, SICMF and SIPMO), written on the inputs of the experts of the Italian Allied Committee on ONJ (IAC-ONJ). The conference focused on the topic of MRONJ, and in particular on the common practices at risk of inappropriateness in MRONJ diagnosis and therapy, as well as on MRONJ prevention and the dental management of patients at risk of MRONJ. It is a matter of cancer and osteometabolic patients that are at risk since being exposed to several drugs with antiresorptive (i.e., bisphosphonates and denosumab) or, more recently, antiangiogenic activities. At the same time, the Conference traced for dentists and oral surgeons some easy applicable indications and procedures to reduce MRONJ onset risk and to diagnose it early. Continuous updating on these issues, so important for the patient community, is recommended.

Aim: Coffee intake is common during pregnancy. However, the influence of coffee and caffeine on pregnancy has not yet been fully determined. Some studies show that high coffee intake could cause mi...

Yellow fever (YF) is an acute viral hemorrhagic disease caused by the YF virus (arbovirus) which continues to cause severe morbidity and mortality in Africa. A case of YF was confirmed in Nigeria on the 12th of September 2017, 21 years after the last confirmed case. The patient belongs to a nomadic population with a history of low YF vaccination uptake, in the Ifelodun Local Government Area (LGA) of Kwara State, Nigeria. An active case search in Ifelodun and its five contiguous LGAs led to the listing of 55 additional suspect cases of YF within the period of the outbreak investigation between September 18 to October 6, 2017. The median age of cases was 15 years, and 54.4% were males. Of these, blood samples were collected from 30 cases; nine tested positive in laboratories in Nigeria and six were confirmed positive for YF by the WHO reference laboratory in the region; Institut Pasteur, Dakar. A rapid YF vaccination coverage assessment was carried out, resulting in a coverage of 46% in the LGAs, with 25% of cases able to produce their vaccination cards. All stages of the yellow fever vector, Aedes mosquito were identified in the area, with high larval indices (House and Breteau) observed. In response to the outbreak, YF surveillance was intensified across all States in Nigeria, as well as reactive vaccination and social mobilisation campaigns carried out in the affected LGAs in Kwara State. A state-wide YF preventive campaign was also initiated.

INTRODUCTION: Ultrasound (US) imaging has rapidly increased its application in almost every medical field. Many universities worldwide provide teaching of US for undergraduates in their curricula. Emerging evidence is supporting the use of ultrasonography to improve also non-US skills and knowledge of medical students. OBJECTIVES: The purpose of this review is to understand if the integration of US lessons into medical students’ curriculum improves their learning of physical examination and enhances their skills when performing it. METHODS: We performed a systematic review of literature by searching three electronic medical databases. We included studies of any level of evidence published in peer-reviewed journals. Evaluated data were extracted using the PICO framework and critically analyzed. PRISMA guidelines were applied; we excluded all the articles evaluated with serious risk of bias and/or low methodological quality. RESULTS: We included 15 articles, accounting for more than 1643 medical students involved from five different countries and 14 various academical institutions. Eight out of nine studies (88.9%) reported an improvement of practical physical examination scores by students exposed to ultrasound lectures. Eleven out of eleven studies (100%), which administered self-assessment questionnaires, reported strong agreement among students that ultrasound lectures helped them learning and understanding the physical exam and improved their confidence and skills. CONCLUSIONS: Increasing evidence shows that incorporating ultrasound in medical students’ curriculum might improve their ability and confidence when learning and performing a physical exam. This significant tendency needs to be corroborated at a deeper level by further studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40670-020-00921-4) contains supplementary material, which is available to authorized users.

Dental extraction has often been described as the main trigger event of osteonecrosis of the jaws (ONJ). This longitudinal hospital-based study aimed to evaluate the outcome at 2 years of a standardized medical-surgical protocol for dental extraction, combined with platelet rich-plasma (PRP) application, compared with conventional protocol not combined with PRP or any other autologous platelet concentrate in cancer (ONC) and osteometabolic (OST) patients, at risk of bisphosphonate (BP)-related ONJ. Twenty patients were consecutively recruited: six received BPs for cancer skeletal-related events (34.17 &plusmn, 19.97 months), while fourteen received BPs for metabolic bone disease (74.5 &plusmn, 34.73 months). These patients underwent a standardized protocol for dental extraction, combined with autologous PRP application in the post-extraction socket. A total of 63 dental extractions were performed (24 and 39 in ONC and OST groups, respectively). As controls, historical cases, derived from the literature and including 171 ONC and 734 OST patients, were considered. The outcome of the surgical treatment was successful in all patients treated with PRP: two years after extraction, no patient had clinical or radiological signs of ONJ. When this datum was compared with historical controls, no statistically significant differences were found (p &gt, 0.1). The combination of a standardized medical-surgical protocol with PRP application may contribute to limit the occurrence of BP-related ONJ, in both ONC and OST patients. Additional prospective studies with a larger patient sample are necessary to confirm this datum.

Background: The aim of the present work was to analyze a 10-year retrospective series of surgically treated medication-related osteonecrosis of the jaws (MRONJ) cases, reporting the clinical outcome and success rate for each adopted procedure in order to draw a treatment algorithm that is able to standardize clinical decision making and maximize the success of oral surgical treatment of MRONJ. Methods: Different surgical approaches were categorized taking into consideration two variables a) hard tissue management (defined as debridement, saucerization or marginal resective surgery of maxillary necrotic bone) and b) soft tissue management (defined as type of flap design and related modality of wound-healing). Results: For the retrospective cohort study, 103 MRONJ patients were enrolled and a total of 128 surgical procedures were performed. The role of radical-intended surgery using local flaps in MRONJ treatment was investigated, as well as palliative treatments. All stage I&ndash, II patients completely healed when a combination of radical necrotic bone surgery associated with a first intention healing of soft tissues was obtained. In stage III, when a patient was not eligible for maxillo-facial surgery, the use of palliative surgical strategies was effective in symptom relief in order to maintain a better quality of life for the duration of the patient&rsquo, s life. Conclusions: Oral surgery with radical intent associated with a flap design able to ensure first intention healing might represent a valid option for the majority of MRONJ patients. The designed decision tree allows clinicians to assess individual surgical approaches for MRONJ treatment in accordance with patient-centered outcomes and surgical skills.

The bioengineering and medical and biomedical fields are ever closer, and they manage to obtain surprising results for the development of new devices. The field of simulations and studies in silica has undergone considerable development in recent years, favoring the advancement of medicine. In this manuscript, a study was carried out to evaluate the force distribution on the implant components (In-Kone® Universal) and on the peri-implant tissues subjected to loading. With the finite element analysis and the Von Mises method, it was possible to evaluate this distribution of forces both at 0 degrees (occlusal force) and at 30 degrees; the applied force was 800 N. The obtained results on this new type of connection and on all the implant components are satisfactory; the distribution of forces appears optimal even on the peri-implant tissues. Surely, studies like this help to obtain ever more performing devices, improving both the clinic and the predictability of rehabilitations.

Gliomas represent over 70% of all brain tumors, they are highly invasive and structurally vascular neoplasms. Despite the latest technological advance in neuro-surgery the survival of patients with high-grade glioma remains poor. The lack of robust treatment options has propelled the search for new markers that may able allow the identification of patients who can benefit from molecularly targeted therapies. The Hippo signaling pathway is considered as a key regulator of tissue homeostasis, cell proliferation and apoptosis, and alterations of this pathway seem to contribute to tumorigenesis. Yes-associated protein (YAP1) is a downstream target of the Hippo pathway which acts as a transcription co-activator. In cancer, YAP1 has been reported to function either as an oncogene or tumor suppressor, depending on the cell context. The aim of this study was to examine the expression of YAP1, Survivin and LATS1 kinase activity in human astroglial tumors with different grades of malignancy. Moreover, we also investigated the expression of miR-221 and miR-10b and their relationship with core molecules of the Hippo pathway. Our results showed the overexpression of YAP1 and Survivin as well as a decreased activity of large tumor suppressor 1 (LATS1) in high-grade glioblastoma versus anaplastic astrocytoma and low-grade glioma. Furthermore, we also demonstrated that miR-221 and miR-10b are specifically involved in Hippo signaling via LATS1 regulation and that their knockdown significantly decreased glioma cell proliferation. This preliminary data confirmed the crucial role of the Hippo pathway in cancer and suggested that miR-221 and miR-10b could be potential therapeutic targets for glioma treatment.

TBI is the main cause of death and disability in individuals aged 1–45 in Western countries. One of the main challenges of TBI at present is the lack of specific diagnostic biomarkers, especially for mild TBI (mTBI), which remains currently difficult to value in clinical practice. In this context MiRNAs may be important mediators of the profound molecular and cellular changes that occur after TBI in both the short and the long term. Recently, plasma miRNAs profiling in human TBI, have revealed dynamic temporal regulation of miRNA expression within the cortex. Aim of this study was to select a specific miRNAs panel for mTBI, by focusing the research on the prognostic meaning of miRNAs in the hours following the trauma, in order to be able to use this MIRNAs as potential biomarkers useful for monitoring the follow up of mild TBI. Serum levels of 17 miRNAs were measured by RT-quantitative polymerase chain reaction (qPCR) in 20 patients with mTBI at three different time-points (0h, 24h, 48h) and in 10 controls. For 15 miRNAs we found a significant differences in the comparison among the three time points: for each of these miRNAs the values were greater at baseline and progressively reduced at 24h and 48h. These data allow us to consider the miRNAs included in panel as sensitive and specific biomarkers for mTBI, useful in monitoring the post-trauma period.

Objective. The objective of the present review is to assess the implant survival, marginal bone loss, and biomechanical features of narrow-diameter implants (2.5-3.5 mm) supporting or retaining full-arch fixed or removable restorations. Materials and Methods. Three operators screened the literature (PubMed, Cochrane Library, and Google Scholar) and performed a hand search on the main journals that focus on implantology until 24 March 2019. Only articles that considered full-arch restorations supported or retained by narrow-diameter implants (2.5-3.5 mm) were considered if they have a minimum of 10 patients and a mean follow-up of at least 6 months. The outcome variables were survival of implants and marginal bone loss. The review was performed according to the PRISMA statements. Risk of bias assessment was evaluated. Failure rates were analyzed using random effect Poisson regression models to obtain the summary estimate of 5-year survival rate and marginal bone loss. Results. A total of nine papers were finally selected, reporting a high survival rate of the implants. Eight studies focused only on the mandible while one study reported data from both mandible and maxilla. All studies reported on removable restorations; none focused on fixed rehabilitations. The estimated survival rate for 5 years of follow-up was calculated to be 92.25% for the implants. The estimated marginal bone loss after 5 years was calculated to be 1.40 mm. No study reported implant fractures. Conclusions. With the limitations of the present study, there is evidence that 2.5-3.5 mm narrow-diameter implants retaining a removable restoration can be a successful treatment in fully edentulous patients. No data on fixed restorations was available.

Osteonecrosis of the jaw (ONJ) is an adverse drug reaction described as the progressive destruction and death of bone that affects the mandible and maxilla of patients exposed to the treatment with medications known to increase the risk of disease, in the absence of a previous radiation treatment. Tooth extraction often precedes the manifestation of ONJ; indeed, it is sometimes called trigger event and it have also been considered as risk factors for the onset of ONJ. As a consequence, some of the guidelines recommend avoiding tooth extractions in patients at risk of ONJ; however, a growing body of evidence indicates that dental/periodontal infection prior to extraction, rather than dental extraction may represent the main local risk factor for ONJ. Ten patients at risk of ONJ have undergone tooth extractions. They were identified and included in our retrospective monocentric clinical investigation. Patients underwent tooth extractions with standardized procedures (PROMaF protocol), and bone biopsies were taken. Extractions were performed due to symptomatic, non-restorable teeth in patient at risk of ONJ; histological findings of ONJ were observed in all samples. This outcome may highlight that the proof of non‐exposed ONJ might be the histopathologic confirmation of necrotic bone, as stated by European task force on MRONJ. Additionally, alveolar biopsy should possibly be taken in every case of suspected ONJ, which needs an proper and prompt management for successful healing.

Osteonecrosis of the jaw (ONJ) is a well-known adverse drug reaction to bisphosphonate (BP) treatment. ONJ diagnosis is usually based on the patient’s medical/medication histories and on the clinical/radiological features of necrotic bone (frequently exposed). Furthermore, in case of mandibular involvement, patients may present pain and/or hypesthesia of the inferior alveolar nerve. There are no pathognomonic clinical and radiological signs of ONJ, and in doubtful cases, the histologic examination is recommended. We report a case of a woman attending to our sector of Oral Medicine (AOUP “P. Giaccone” Palermo, Italy) with a mandibular bone exposure after implants loss and a medical history of BPs. Biopsy specimens demonstrated proliferation of oral squamous cell carcinoma (OSCC). Even if the role of biopsy in diagnosis ONJ is still a controversial issue, it is mandatory in case of OSCC suspicious.

Recently, interest has grown by focusing on the evaluation of a molecule already produced in the human body such as hyaluronic acid (HA), as an application to the surface of the titanium implant. Its osteo-conductive characteristics and positive interaction with the progenitor cells responsible for bone formation, consequently, make it responsible for secondary stability. The aim of this work was to analyze the various surface treatments in titanium implants, demonstrating that the topography and surface chemistry of biomaterials can correlate with the host response; also focusing on the addition of HA to the implant surface and assessing the biological implications during early stages of recovery. Used as a coating, HA acts on the migration, adhesion, proliferation and differentiation of cell precursors on titanium implants by improving the connection between implant and bone. Furthermore, the improvement of the bioactivity of the implant surfaces through HA could therefore facilitate the positioning of the dental prosthesis precisely in the early loading phase, thus satisfying the patients’ requests. It is important to note that all the findings should be supported by further experimental studies in animals as well as humans to evaluate and confirm the use of HA in any field of dentistry.

Preoperative anxiety is a common reaction exhibited by up to 80% of patients who are scheduled for surgical procedures and characterized by psychological and physical changes which may affect their perioperative period. Our aim is to report the most up-to-date evidence on preoperative anxiety in brain surgery patients through a systematic analysis of the studies produced in the last decades. We performed a systematic review of literature by searching PubMed, Embase, and Cochrane Library databases. Data were extracted using the Population, Intervention, Comparison, Outcome framework and critically analyzed. PRISMA guidelines were applied, and the risk of bias of the included studies was assessed using the Risk of bias (RoB) 2 and ROBINS tools, as was the methodological quality, following GRADE criteria. We included 27 articles, accounting for 2558 patients in twelve different countries. The prevalence of preoperative anxiety ranged from 17 up to 89%, higher in female patients. Preoperative anxiety was associated with lower quality of life and cognitive performance, higher need for information, poorer memory and attention, longer hospitalization, depressive symptoms, and increase of physical disability; no correlation with survival rate was found. Seven randomized controlled trials attested the efficacy of acupuncture, music therapy, virtual reality, and pharmacological support in lowering anxiety levels. Preoperative anxiety is a common phenomenon that could negatively affect the perioperative period of brain surgery patients: this is something that should not be neglected to achieve better care through early prevention and optimal management. Supplementary Information The online version contains supplementary material available at 10.1007/s10143-021-01498-1.

Introduction Regenerative procedures have become common in the medical and dentistry rehabilitation fields. Often, tissue regeneration maneuvers are necessary to rehabilitate patients in a safe and predictable manner. The aim of this narrative review was to highlight the molecular implications during regenerative surgery. Evidence acquisition The analysis of the literature was conducted on the main scientific databases Pubmed, Scopus, MDPI. Evidence synthesis After a screening of 66 results only 8 were included. Conclusions Knowing these molecular features, it is possible to highlight which are the biomaterials that offer greater potential and identify the best protocols according to the surgical needs.

The goal of this investigation was to identify potential risk factors to predict the onset of medication-related osteonecrosis of the jaw (MRONJ). Through the identification of the multiple variables positively associated to MRONJ, we aim to write a paradigm for integrated MRONJ risk assessment built on the combined analysis of systemic and local risk factors. The characteristics of a cohort of cancer patients treated with zoledronic acid and/or denosumab were investigated, beyond the set of proven risk factors a new potential one, the intake of new molecules for cancer therapy, was addressed. Registered data were included in univariate and multivariate logistic regression analysis in order to individuate significant independent predictors of MRONJ, a propensity score-matching method was performed adjusting by age and sex. Univariate logistic regression analysis showed a significant effect of the parameters number of doses of zoledronic acid and/or denosumab (OR = 1.03, 95% CI = 1.01–1.05, p = 0.008) and chemotherapy (OR = 0.35, 95% CI = 0.17–0.71, p = 0.008). The multiple logistic regression model showed that breast, multiple myeloma, and prostate cancer involved a significantly higher risk compared to lung cancer, a significant effect of the combined variables number of doses of zoledronic acid and/or denosumab (OR = 1.03, 95% CI = 1.01–1.06), p-value = 0.03) and exposure to novel molecule treatment (OR = 34.74, 95% CI = 1.39–868.11, p-value = 0.03) was observed. The results suggest that a risk assessment paradigm is needed for personalized prevention strategies in the light of patient-centered care.

Spinal muscular atrophy (SMA) type 1 is a severe infantile autosomal-recessive neuromuscular disorder caused by a survival motor neuron 1 gene (SMN1) mutation and characterized by progressive muscle weakness. Without supportive care, SMA type 1 is rapidly fatal. The antisense oligonucleotide nusinersen has recently improved the natural course of this disease. Here, we investigated, with a functional proteomic approach, cerebrospinal fluid (CSF) protein profiles from SMA type 1 patients who underwent nusinersen administration to clarify the biochemical response to the treatment and to monitor disease progression based on therapy. Six months after starting treatment (12 mg/5 mL × four doses of loading regimen administered at days 0, 14, 28, and 63), we observed a generalized reversion trend of the CSF protein pattern from our patient cohort to that of control donors. Notably, a marked up-regulation of apolipoprotein A1 and apolipoprotein E and a consistent variation in transthyretin proteoform occurrence were detected. Since these multifunctional proteins are critically active in biomolecular processes aberrant in SMA, i.e., synaptogenesis and neurite growth, neuronal survival and plasticity, inflammation, and oxidative stress control, their nusinersen induced modulation may support SMN improved-expression effects. Hence, these lipoproteins and transthyretin could represent valuable biomarkers to assess patient responsiveness and disease progression.

We read the letter from Dr. Fusco and colleagues with great interest, and we would like to thank them for the stimulating comments regarding our paper “Medication-Related Osteonecrosis of the Jaws and CDK4/6 Inhibitors: A Recent Association” [...]

The aim of this study was a comparative statistical analysis of three categories of maxillary odontogenic cysts, evaluating frequency in relation to localization (mandibular or maxillary region), age and gender of patients. The study was a retrospective cohort study conducted at the University Hospital of Messina. Three hundred and fifty-six maxillary odontogenic cysts were classified into 283 inflammatory, 43 developmental and 30 neoplastic cysts. Female patients are more affected by developmental odontogenic cysts, while male patients are more affected by inflammatory odontogenic cysts. Both the mandibular and maxillary regions were affected mainly by inflammatory odontogenic cysts, no significantly statistic relationship was found between lesions and age. A significant association between odontogenic cyst lesions and patient gender was found. No significant association between histological features of lesion and age of patient was observed, nor subtype of odontogenic disease and localization (mandibular or maxillary).

Purpose: After regulatory restrictions for terfenadine and astemizole in ‘90s, only scarce evidence on proarrhythmic potential of antihistamines has been published. We evaluate the risk of ventricular tachyarrhythmia (VA) related to the use of individual antihistamines. Methods: A matched case-control study nested in a cohort of new users of antihistamines was conducted within the EU-funded ARITMO project. Data on 1997–2010 were retrieved from seven healthcare databases: AARHUS (Denmark), GEPARD (Germany), HSD and ERD (Italy), PHARMO and IPCI (Netherlands) and THIN (UK). Cases of VA were selected and up to 100 controls were matched to each case. The odds ratio (OR) of current use for individual antihistamines (AHs) was estimated using conditional logistic regression. Results: For agents largely used to prevent allergic symptoms, such as cetirizine, levocetirizine, loratadine, desloratadine and fexofenadine, we found no VA risk. A statistically significant, increased risk of VA was found only for current use of cyclizine in the pooled analysis (ORadj, 5.3; 3.6–7.6) and in THIN (ORadj, 5.3; 95% CI, 3.7–7.6), for dimetindene in GEPARD (ORadj, 3.9; 1.1–14.7) and for ebastine in GEPARD (ORadj, 3.3; 1.1–10.8) and PHARMO (ORadj, 4.6; 1.3–16.2). Conclusions: The risk of VA associated with a few specific antihistamines could be ascribable to heterogeneity in pattern of use or in receptor binding profile.

In a recent study our research group described a non-invasive sampling procedure based on [...]

The fluorescence method is an innovative technique used by pathologists for examining body mucosa, and for the abnormalities tissue screening, potentially leading to the earlier discovery of pre-cancer, cancer or other disease processes. The early detection is one of the best mechanisms for enabling treatment success, increasing survival rates and maintaining a high quality of life. The purpose of this review is to evaluate the clinical efficiency of this diagnostic tool applied to the oral cavity (VELscope®). A literature systematic review has been performed. The initial research provided 53 results after applying the inclusion and exclusion criteria, and after a manual screening of the abstracts by the authors, only 25 results were eligible for review. The results and data contained in all the researches, no older than 10 years, were manually evaluated, and provided useful information on this diagnostic method. The VELscope® mean value about sensitivity and specificity resulted of 70.19% and 65.95%, respectively, by results analysis, but despite this some studies disagree about its clinical effectiveness, and this diagnostic method is still much debated in scientific and clinical medical literature. Surely being able to have efficient and effective tools from this point of view could help the clinician in the diagnosis, and also make timelier the pharmacological or surgical therapy, improving the quality of life of the patient, and in some cases guaranteeing a longer survival term.

The purpose of the present study was to estimate the prevalence of cyclin-dependent kinase (CDK) 4/6 inhibitors use among cancer patients from the medication-related osteonecrosis of the jaw (MRONJ) cohort of the University of Messina. We retrospectively reviewed the records of all patients with either intravenous bisphosphonates or denosumab-related MRONJ reported in the electronic health records of the Unit of Oral Surgery, School of Dentistry, University of Messina between the first quarter of 2018 and the first quarter 2020 to identify eligible patients. We observed six cases of MRONJ associated with CDK4/6 inhibitors concomitantly with intravenous bisphosphonates and/or denosumab in breast cancer patients. The CDK4/6 inhibitors registered were palbociclib (n = 5) and abemaciclib (n = 1). Data of cancer patients diagnosed with MRONJ in the same period (n = 10) were extracted for comparison. The comparative assessment with this group of patients showed a similar distribution of MRONJ stage ranged and clinical course after treatment. The degree of risk for osteonecrosis in patients taking these new classes of drugs is uncertain but warrants awareness and close monitoring. The role of premedication dental evaluation as a prevention strategy has been acknowledged for cancer patients about to initiate intravenous bisphosphonates and/or denosumab for treatment of bone metastasis, but additional attention should be paid to whom are assuming CDK4/6 inhibitors because of their oral adverse events.

Background Yellow fever outbreaks are documented to have a considerable impact not only on the individuals but on the health system with significant economic implications. Efforts to eliminate yellow fever outbreaks globally through the EYE strategy remains important following outbreaks in Africa, Nigeria included. The outbreaks reported in Nigeria, since 2017 and the response efforts provide an opportunity to document and guide interventions for improving future outbreaks in Nigeria and other countries in Africa. Methods We reviewed the available yellow fever surveillance and vaccination response data between September 2017 and September 2019 across the 36 states across Nigeria. We described the epidemiology of the difference outbreaks and the periods for all interventions. We also documented the emergency vaccination responses as well as preventive mass vaccinations implemented towards improving population immunity and limiting epidemic potentials in Nigeria. Results A total of 7894 suspected cases with 287 laboratory-confirmed cases were reported in Nigeria between September 2017 and September 2019 with a mean age of 19 years and a case fatality of 2.7% amongst all reported cases. Outbreaks were confirmed in 55 LGAs with most of the outbreaks across four major epicentres in Kwara/Kogi, Edo, Ebonyi and Bauchi states. In response to these outbreaks, eight reactive vaccination campaigns, supported through ICG applications, were implemented. The duration for responding to the outbreaks ranged from 15 to 132 days (average 68 days) and a total of 45,648,243 persons aged . Conclusions Nigeria experienced intermediate outbreaks of yellow fever between September 2017 and 2019 with vaccination responses conducted to control these outbreaks. However, there are delays in the timeliness of responses and more efforts required in improving reporting, response times and preparedness to further prevent morbidity and mortality from the yellow fever disease outbreaks. These efforts, including improving routine yellow fever coverage, contribute towards improving population immunity and other activities related to achieving the goals of the EYE strategy.

Oral surgery has undergone dramatic developments in recent years due to the use of biomaterials. The aim of the present review is to provide a general overview of the current biomaterials used in oral surgery and to comprehensively outline their impact on post-operative wound healing. A search in Medline was performed, including hand searching. Combinations of searching terms and several criteria were applied for study identification, selection, and inclusion. The literature was searched for reviews published up to July 2020. Reviews evaluating the clinical and histological effects of biomaterials on post-operative wound healing in oral surgical procedures were included. Review selection was performed by two independent reviewers. Disagreements were resolved by a third reviewer, and 41 reviews were included in the final selection. The selected papers covered a wide range of biomaterials such as stem cells, bone grafts, and growth factors. Bioengineering and biomaterials development represent one of the most promising perspectives for the future of oral surgery. In particular, stem cells and growth factors are polarizing the focus of this ever-evolving field, continuously improving standard surgical techniques, and granting access to new approaches.

In 2015, the World Health Organization substantially revised its guidance for vaccination coverage cluster surveys (revisions were finalized in 2018) and has since developed a set of accompanying resources, including definitions for standardized coverage indicators and software (named the Vaccination Coverage Quality Indicators - VCQI) to calculate them. The current WHO vaccination coverage survey manual was used to design and conduct two nationally representative vaccination coverage surveys in Nigeria – one to assess routine immunization and one to measure post-measles campaign coverage. The primary analysis for both surveys was conducted using VCQI. In this paper, we describe those surveys and highlight some of the analyses that are facilitated by the new resources. In addition to calculating coverage of each vaccine-dose by age group, VCQI analyses provide insight into several indicators of program quality such as crude coverage versus valid doses, vaccination timeliness, missed opportunities for simultaneous vaccination, and, where relevant, vaccination campaign coverage stratified by several parameters, including the number of previous doses received. The VCQI software furnishes several helpful ways to visualize survey results. We show that routine coverage of all vaccines is far below targets in Nigeria and especially low in northeast and northwest zones, which also have highest rates of dropout and missed opportunities for vaccination. Coverage in the 2017 measles campaign was higher and showed less geospatial variation than routine coverage. Nonetheless, substantial improvement in both routine program performance and campaign implementation will be needed to achieve disease control goals.

Human gingival fibroblasts (GF) and human oral mucosa epithelial cells (EC) with an inflammatory phenotype represent a valuable experimental paradigm to explore the curative activity of agents to be used in oral mucositis. The role of cannabinoid receptor 2 (CB2) has not yet been investigated in oral mucositis. The aim of this study was to evaluate the therapeutic potential of &beta, Caryophyllene (BCP), a CB2 agonist, in an in vitro model of oral mucositis. GF and EC were stimulated with LPS (2 &micro, g/mL) alone or in combination with BCP, a group of LPS challenged GF and EC were treated with BCP and AM630, a CB2 antagonist. LPS increased the inflammatory cytokines TNF-&alpha, IL-1&beta, IL-6 and IL-17A whereas it decreased the anti-inflammatory cytokine IL-13. The upstream signals were identified in an augmented expression of NF-&kappa, B and STAT-3 and in reduced mRNA levels of PPAR&gamma, and PGC-1&alpha, BCP blunted the LPS-induced inflammatory phenotype and this effect was reverted by the CB2 antagonist AM630. These results suggest that CB2 receptors are an interesting target to develop innovative strategies for oral mucositis and point out that BCP exerts a marked curative effect in a preclinical model of oral mucositis which deserves to be confirmed in a clinical setting.

Background Epigenetics of vitiligo was evaluated in few studies. In particular, the role of miR-21, a microRNA involved in various processes, including melanogenesis, was never investigated. Objective Evaluation of serum levels of miR-21-5p in vitiligo patients and miR-21-5p effects on melanogenesis. Methods We measured serum levels of miR-21-5p in 40 patients affected by nonsegmental vitiligo and 40 sex- and age-matched healthy controls. Next, normal human melanocytes were transfected with miR-21-5p to study the effects of this microRNA, which targeted some proteins involved in melanogenesis pathway like SOX5, beta-catenin, cyclin-dependent kinase 2 (CDK2), and MITF. Results The expression of miR-21-5p in vitiligo patients was 3.6–4454.4 fold (mean 990.4 ± 1397.9) higher than in controls. The relative expression of miR-21-5p was directly and significantly correlated with disease severity, defined by VASI (Vitiligo Area and Severity Index) score (Rho = 0.89, p = 10−7), but not other individual or clinical characteristics. In the second part of the study, a significant reduction of SOX5, beta-catenin and CDK2 protein expression and increase of MITF protein expression was observed in cultured melanocytes after 24 h trasfection with miR-21-5p. Conclusion According to literature, miR-21-5p upregulation and consequent SOX5 downregulation should upregulate melanogenesis, while vitiligo is characterized by skin depigmentation. Our results suggest that current knowledge of the pathogenesis of vitiligo is probably incomplete. Clinical manifestations could result from an altered balance between metabolic pathways with contrasting effects. In this view, miR-21-5p upregulation might be a tentative compensation mechanism. Further studies appear necessary to confirm and better understand our results and their importance.