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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.

Pituitary adenomas (PAs), usually benign lesions, can sometimes present with “aggressive” features (rapid growth, local invasiveness, scarce response to conventional treatments). Despite the fact that a few genetic alterations have been associated to this clinical behavior, the role of epigenetic modifications, mainly methylation and miRNAs activity, is now opening new frontiers in this field. We evaluated the methylation profile of 21 PA (11 GH-omas, 10 nonfunctioning tumors—NFPAs) samples from TNS surgery and 5 normal pituitaries, collected at our neurosurgery between 2015 and 2017. DNA was extracted and sequenced, selecting 184,841 target regions. Moreover, methylation profiles were correlated with demographic, radiological, and clinicopathological features. NFPAs showed higher methylation levels vs. GH-omas, with 178 differentially methylated regions (DMRs) mainly consisting of noncoding and intronic sequences, and mostly localized in the open sea regions. We also found three hypermethylated genes (C7orf50, GNG7, and BAHCC1) involved in tumorigenesis processes and potentially influencing pituitary tumor pathophysiology. Among the clinicopathological features, only the maximum diameter resulted significantly higher in NFPAs. Our data provide further evidence of the complex epigenetic background of pituitary tumors. In line with the current literature, we confirmed a significant prevalence of hypermethylation in NFPAs vs. GH-omas, whose pathophysiological consequence is yet to be defined.

Background Edo State Surveillance Unit observed the emergence of a disease with “no clear-cut-diagnosis”, which affected peri-urban Local Government Areas (LGAs) from September 6 to November 1, 2018. On notification, the Nigeria Centre for Disease Control deployed a Rapid Response Team (RRT) to support outbreak investigation and response activities in the State. This study describes the epidemiology of and response to a large yellow fever (YF) outbreak in Edo State. Methods A cross-sectional descriptive outbreak investigation of YF outbreak in Edo State. A suspected case of YF was defined as “Any person residing in Edo State with acute onset of fever and jaundice appearing within 14 days of onset of the first symptoms from September 2018 to January 2019”. Our response involved active case search in health facilities and communities, retrospective review of patients’ records, rapid risk assessment, entomological survey, rapid YF vaccination coverage assessment, blood sample collection, case management and risk communication. Descriptive data analysis using percentages, proportions, frequencies were made. Results A total of 209 suspected cases were line-listed. Sixty-seven (67) confirmed in 12 LGAs with 15 deaths [Case fatality rate (CFR 22.4%)]. Among confirmed cases, median age was 24.8, (range 64 (1-64) years; Fifty-one (76.1%) were males; and only 13 (19.4%) had a history of YF vaccination. Vaccination coverage survey involving 241 children revealed low YF vaccine uptake, with 44.6% providing routine immunisation cards for sighting. Risk of YF transmission was 71.4%. Presence of Aedes with high-larval indices (House Index ≥5% and/or Breteau Index ≥20) were established in all the seven locations visited. YF reactive mass vaccination campaign was implemented. Conclusion Edo State is one of the states in Nigeria with the highest burden of yellow fever. More males were affected among the confirmed. Major symptoms include fever, jaundice, weakness, and bleeding. Majority of surveillance performance indicators were above target. There is a high risk of transmission of the disease in the state. Low yellow fever vaccination coverage, and presence of yellow fever vectors (Ae.aegypti, Ae.albopictus and Ae.simpsoni) are responsible for cases in affected communities. Enhanced surveillance, improved laboratory sample management, reactive vaccination campaign, improved yellow fever case management and increased risk communication/awareness are very important mitigation strategies to be sustained in Edo state to prevent further spread and mortality from yellow fever.

Objective Implantology represents the gold standard for oral rehabilitation, unfortunately, often, despite there are no local contraindications to this type of rehabilitation, there are uncertainties regarding the general health of our patients. Many patients nowadays take bisphosphonate drugs, often without first seeking advice from an oral surgeon or a dentist. The purpose of this review is precisely to highlight any contraindications to this type of treatment reported in the literature, in patients who take or have taken bisphosphonate drugs. Methods For this study the scientific information sources were consulted using as search terms “(“bisphosphonate AND “dental implant”)”, obtaining 312 results, these were subsequently skimmed according to the inclusion and exclusion criteria, and further evaluated their relevance to the study and the presence of requested outcomes. Results Only 9 manuscripts (RCTs, Multicentric studies and Clinical Trials) were included in this review, as they respected the parameters of this review, they were analyzed and it was possible to draw important results from them. Surely from this study it is understood that the use of bisphosphonate drugs does not represent an absolute contraindication to implant therapy, it is evident how adequate pharmacological prophylaxis, and an adequate protocol reduce the risks regarding implant failures. Furthermore, the values of marginal bone loss over time seem, even if not statistically significant, to be better in implant rehabilitation with bisphosphonate drugs association. Only a few molecules like risedronate, or corticosteroids, or some conditions like smoking or diabetes have shown a high risk of surgical failure. Conclusion Although this study considered different studies for a total of 378 patients and at least 1687 different dental implants, showing better results in some cases for dental implant therapy in cases of bisphosphonate intake, further clinical, randomized and multicentric studies are needed, with longer follow-ups, to fully clarify this situation which often negatively affects the quality of life of our patients and places clinicians in the face of doubts.

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.

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.

Summary: Background: We undertook a Grand Challenges in Global Eye Health prioritisation exercise to identify the key issues that must be addressed to improve eye health in the context of an ageing population, to eliminate persistent inequities in health-care access, and to mitigate widespread resource limitations. Methods: Drawing on methods used in previous Grand Challenges studies, we used a multi-step recruitment strategy to assemble a diverse panel of individuals from a range of disciplines relevant to global eye health from all regions globally to participate in a three-round, online, Delphi-like, prioritisation process to nominate and rank challenges in global eye health. Through this process, we developed both global and regional priority lists. Findings: Between Sept 1 and Dec 12, 2019, 470 individuals complete round 1 of the process, of whom 336 completed all three rounds (round 2 between Feb 26 and March 18, 2020, and round 3 between April 2 and April 25, 2020) 156 (46%) of 336 were women, 180 (54%) were men. The proportion of participants who worked in each region ranged from 104 (31%) in sub-Saharan Africa to 21 (6%) in central Europe, eastern Europe, and in central Asia. Of 85 unique challenges identified after round 1, 16 challenges were prioritised at the global level; six focused on detection and treatment of conditions (cataract, refractive error, glaucoma, diabetic retinopathy, services for children and screening for early detection), two focused on addressing shortages in human resource capacity, five on other health service and policy factors (including strengthening policies, integration, health information systems, and budget allocation), and three on improving access to care and promoting equity. Interpretation: This list of Grand Challenges serves as a starting point for immediate action by funders to guide investment in research and innovation in eye health. It challenges researchers, clinicians, and policy makers to build collaborations to address specific challenges. Funding: The Queen Elizabeth Diamond Jubilee Trust, Moorfields Eye Charity, National Institute for Health Research Moorfields Biomedical Research Centre, Wellcome Trust, Sightsavers, The Fred Hollows Foundation, The Seva Foundation, British Council for the Prevention of Blindness, and Christian Blind Mission. Translations: For the French, Spanish, Chinese, Portuguese, Arabic and Persian translations of the abstract see Supplementary Materials section.

Summary We present a global atlas of 4,728 metagenomic samples from mass-transit systems in 60 cities over 3 years, representing the first systematic, worldwide catalog of the urban microbial ecosystem. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance (AMR) markers, and genetic elements, including 10,928 viruses, 1,302 bacteria, 2 archaea, and 838,532 CRISPR arrays not found in reference databases. We identified 4,246 known species of urban microorganisms and a consistent set of 31 species found in 97% of samples that were distinct from human commensal organisms. Profiles of AMR genes varied widely in type and density across cities. Cities showed distinct microbial taxonomic signatures that were driven by climate and geographic differences. These results constitute a high-resolution global metagenomic atlas that enables discovery of organisms and genes, highlights potential public health and forensic applications, and provides a culture-independent view of AMR burden in cities., Graphical abstract, Highlights • Cities possess a consistent “core” set of non-human microbes • Urban microbiomes echo important features of cities and city-life • Antimicrobial resistance genes are widespread in cities • Cities contain many novel bacterial and viral species, This systematic, worldwide catalog of urban microbiomes represents a metagenomic atlas important for understanding the ecology, virulence, and antibiotic resistance of city-specific microbial communities.

The therapeutic armamentarium for the treatment of oral mucositis is very poor. Catechin and baicalin are two natural flavonoids that have been individually reported to have a curative potential. Flavocoxid is a mixed extract containing baicalin and catechin showing antioxidant effects and anti-inflammatory activity mainly due to a dual inhibition of inducible cyclooxygenase (COX-2), 5-lipoxygenase (5-LOX) and NLRP3 pathway. The aim of this study was to evaluate the anti-inflammatory and anti-oxidant effects of flavocoxid in an “in vitro” model of oral mucositis induced by triggering an inflammatory phenotype in human gingival fibroblasts (GF) and human oral mucosal epithelial cells (EC).GF and EC were challenged with lipopolysaccharide (LPS 2 μg/ml) alone or in combination with flavocoxid (32 μg/ml).Flavocoxid increased Nrf2, prompted a marked reduction in malondialdehyde levels and reduced the expression of COX-2 and 5-LOX together with PGE2, and LTB4 levels. Flavocoxid caused also a great decrease in the expression of NF-κB and turned off NLRP3 inflammasome and its downstream effectors signal, as caspase-1, IL-1β and IL-18 in both GF and EC cells stimulated with LPS.These results suggest a correlation between oxidative stress and NLRP3 activation and indicate that flavocoxid suppresses the inflammatory storm that accompanies oral mucositis. This preclinical evidence deserves to be confirmed in a clinical setting.

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.

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.

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” [...]

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.

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.

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.

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.

During the COVID-19 emergency, the medical operating protocols have been largely modified for reducing any type of contamination risk, for working in a safe way and for making the patient feel in a safe environment. Telemedicine, smart phones and apps could represent important devices for the community, in order to prevent virus trasmission and to perform quick diagnosis and management at medical offices. This manuscript could be useful for clinicians with regard to the current state of the effectiveness of the telephone triage in this COVID-19 epidemic period. Therefore, it could be an important starting point for future perspectives about telemedicine and virtual patient management.

Introduction An Adverse event following immunization (AEFI) is an untoward medical occurrence following immunization and which may not have a necessary causal relationship with the usage of a vaccine. The World Health Organization categories AEFI into two; serious and non-serious. An AEFI is considered serious if it is life-threatening, requires inpatient hospitalization or results in death. The measles vaccine is safe and effective however because it is a live-attenuated injectable vaccine it is more prone to AEFI as compared to non-injectable vaccines when given in large numbers over a short period as is the nature of measles mass vaccination campaigns (MVC). This article describes Nigeria’s experience on AEFI reporting during the 2017/2018 Measles vaccination campaign (MVC). Methods We reviewed various materials which included the Open Data Kit (ODK) which is an open source smartphone-based data collecting tool, operations room reports, measles campaign tally sheets, AEFI line listing forms, the post measles campaign coverage survey report and the report of the AEFI national expert committee review of the 2017/2018 Nigeria measles MVC. Results A total of 6,214 suspected cases of AEFI were line listed from all 36 states and the Federal Capital Territory(FCT) during the 2017/2018 MVC with Fever(38%) and pain at injection site the (30%)most common reports. Overall, 99.7% AEFIs were reported to be non-serious AEFIs, with almost all cases resolved fully with no long-term sequalae.. The national incidence of suspected AEFI per 100,000 population was 16.3 with subnational incidence highest in Kebbi state (101.3/100,000) and lowest in Bayelsa state (0.8/100,000). Conclusion Adequate AEFI reporting, Investigation and management remains important in managing the risk of a disruption of mass campaigns. The deployment of supervisors during campaign may play an important role in improving the identification and reporting of suspected AEFI. Further inquiries about AEFIs during the post campaign coverage evaluation also played a role in improving AEFI reporting and documentation. The real-time, on the spot, follow up by the national operations team helped with decision making and intervention including AEFI investigations and assessments.

Background Measles is a highly infectious disease with great burden and implication on a displaced population with low immunity status. The disease can cause up to 140,000 deaths annually. Internal displacement during supplemental immunization activities often affects optimal reach and coverage of the campaign as people move and implementation and logistic plans are usually disrupted with attendant missed children. This study documented the process of extension of the measles vaccination campaign (MVC) 2018 for five internally displaced persons (IDPs) camps in Benue state, not previously in the microplan, to increase population herd immunity. Methods We obtained population figures and disease surveillance data for five IDPs camps and used it to conduct detailed microplanning to determine the requirement for the conduct of additional days of measles vaccination. Vaccination teams used fixed posts in the camps and temporary posts strategy in designated locations in the host communities. Results The estimated total population of the IDPs was 170,000 with MVC target population of 9374 which was not earlier planned for. There was reported measles outbreaks in IDP camps in both Guma and Makurdi Local Government areas (LGAs) during period of displacement. Microplans requirement determined 10,421 bundled measles vaccine, 30 health workers, 5 vehicles and 15 motorcycles. A total of 7679 out of 9374 (81.9%) of the eligible children aged 9–59 months were vaccinated during the 3 days of the campaign. Conclusion Non-inclusion of plans on internally displaced population in supplemental immunization activities (SIAs) microplans have a potential risk of vaccine preventable diseases (VPDs) outbreak. Future Measles Vaccination campaigns should take cognizance of internal displacement due to insecurity and other humanitarian emergencies.

Introduction The measles supplemental immunisation activity is an effective strategy that improves vaccination coverage and reduces measles-related morbidity and mortality. However, the lack of compliance with microplanning processes, contributes to improper estimation of resources needed for a good SIA in Nigeria. We described the microplanning verification process for 2017/2018 measles vaccination campaign and highlighted the contribution of selected variables to the output of the microplan. Methods We conducted microplanning verification in 2 phases. In Phase 1, we verified at least 30% of randomly selected microplans to assess compliance with the steps and processes of developing good microplans. In Phase 2 we conducted desk review of the entire states micoplans and verified some selected variables at the ward level to corroborate the findings of the microplans. We collected data using open data kit and verification checklist. We conducted data analysis using SPSS and Microsoft Excel version 2016. Results All states in Nigeria verified their wards’ microplans, 21 states (57%) verified more than 30% ,16 states (43%) verified less than 30%, Kebbi State verified the lowest (5.3%). Over 90% of microplans verified complied with the microplanning processes. We observed that overall, there was no significant difference in the number of target population, vaccination teams and qualified vaccinators after the verification process. Conclusion The microplans for 2017/2018 measles vaccination campaign were developed according to the required procesesses, the target population, vaccination teams and qualified vaccinators were physically and realistically estimated. Adherence to microplanning processes is critical to the success of immunization programs.

Introduction Globally, knowledge of health workers has been documented to be key in effective immunisation service delivery. The parenteral route of drug administration is a vital healthcare procedure used in the administration of medicines using needle and syringe. Despite the importance of this procedure, improper handling of the device has resulted in an unsafe practice among health workers who attend to patients receiving injectable medications. A phased measles vaccination campaign (MVC) was conducted in 2017/2018 with a key objectives of training health workers on injection safety. This paper examines the association between improvement on knowledge of health workers through improved training curriculum and their practice on injection safety. Methods We reviewed information on handling and administration of the measles vaccine from the open data kit (ODK) platform finalised microplans and the training curriculum used during the 2015/2016 and 2017/2018 MVC. We analysed our results using paired t-test analysis, SPSS and Microsoft Excel spreadsheet and reported results in frequencies and proportions using charts and tables. Results Our findings revealed more health workers were trained during the 2017/2018 MVC as compared to 2015/2016 MVC. The curriculum adopted during the 2017/2018 MVC showed that multiple techniques were adopted during training compared to only class lectures used during the 2015/2016 MVC. A paired t-test analysis comparing the impact of training on the knowledge of the health workers during 2015/2016 and 2017/2018 MVC revealed significant improvement across five states during the 2017/2018 MVC, with mean ranging from 6.5% in the FCT to 23.7% in Nassarawa state. Conclusion The review of training curriculum and use of multiple training styles during the 2017/2018 MVC improved the knowledge of health workers. Immunisation programmes will benefit from adopting the training curriculum to meet the specific needs of the health workers.

Background Immunisation activities generate sharps and infectious non-sharp waste that have harmful impact on the community and health care workers if disposed of improperly, leading to carbon mono oxide (CO) emissions which contribute to global warming. Health care waste is not effectively managed, especially in some developing countries. However, measles supplemental immunisation activities (SIAs) are used to strengthen routine immunisation system, including waste management. The waste management planning provides an opportunity to build capacity, mobilize resources and strengthen structures to ensure continual disposal of routine immunisation waste. Methods We reviewed the Kebbi State and LGA routine immunisation waste management situation and identified existing gaps; developed and implemented the plan for waste management, including strengthening routine immunisation waste management. The process included, reactivation of measles technical coordination committee, mobilizing resources for funding, and sustenance of immunisation waste management. The health care workforce was trained in safe immunisation waste disposal practices. Results Immunisation waste management committee and the structure was established and strengthened at the state and LGA levels and a total cost of 11,710.70 USD was expended on injection waste management, with an average cost per injection of 0.01 USD. A total of 11,829 safety boxes were incinerated in the state, including those generated from routine immunisation sessions. Twenty-one Local Immunisation Officers, 1097 and 2192 team supervisors and healthcare worker vaccinators respectively were trained on immunisation waste disposal. Conclusion Immunisation waste management strategies protect healthcare workers and reduce the adverse impact on the environment. Improving key areas such as human and financial resources ensures accountability towards sustainable healthcare waste management.

Background Despite the enormous resources committed to the implementation of supplemental immunisation activities in Nigeria, achieving the required coverage (post-campaign survey) to halt the transmission of vaccine-preventable diseases has continued to seem like an impossibility. A vast volume of data is generated and transmitted during mass vaccination campaigns, but this administrative data does not always culminate into improved coverage. The absence of data-informed guidance from stakeholders with long years of experience in planning and implementing mass vaccination campaigns has impeded achieving 95% coverage in measles campaigns in Nigeria. This study reviews the use of data to guide the implementation of the 2017/2018 measles vaccination campaign in Nigeria. Methods A central coordinating body was formed at the national level with the same replicated in every state. Tools were developed to measure the performance of the different phases and activities required for the implementation of a mass vaccination campaign as recommended in the international guidelines. Stakeholders were engaged to help ensure that feedback provided by the national measles technical coordinating committee was implemented at the lower level. Results Monitoring and analysis of daily data submission caused a proper spread of senior supervisors, vaccination posts location during the campaign and helped identify areas targeted for mop-up. Although the verification of states’ microplan increased the operational target population by 11.2%, the process aided the distribution of resources as appropriate. Maps showing the likely areas that needed additional effort to achieve required coverage with recommendation on the necessary approach to be deployed were transmitted to the states implementing the campaign. Conclusion The improvement in the use of data to guide implementation of the Nigeria 2017/2018 measles vaccination campaign caused an increase in the number of states that achieved higher coverage in the post-campaign coverage survey.

Highlights • Three surveys since 2013 show persistently low MCV coverage in much of northern Nigeria. • The 2017–18 measles SIA reached higher and more homogeneous coverage than seen previously. • Geospatial differences exist in the SIA’s reach of previously unvaccinated children. • Nearly all the country is far from the goal of 95% coverage with ≥ 2 doses of MCV. • Routine services need strengthening nationwide, especially in the north., Measles vaccination campaigns are conducted regularly in many low- and middle-income countries to boost measles control efforts and accelerate progress towards elimination. National and sometimes first-level administrative division campaign coverage may be estimated through post-campaign coverage surveys (PCCS). However, these large-area estimates mask significant geographic inequities in coverage at more granular levels. Here, we undertake a geospatial analysis of the Nigeria 2017–18 PCCS data to produce coverage estimates at 1 × 1 km resolution and the district level using binomial spatial regression models built on a suite of geospatial covariates and implemented in a Bayesian framework via the INLA-SPDE approach. We investigate the individual and combined performance of the campaign and routine immunization (RI) by mapping various indicators of coverage for children aged 9–59 months. Additionally, we compare estimated coverage before the campaign at 1 × 1 km and the district level with predicted coverage maps produced using other surveys conducted in 2013 and 2016–17. Coverage during the campaign was generally higher and more homogeneous than RI coverage but geospatial differences in the campaign’s reach of previously unvaccinated children are shown. Persistent areas of low coverage highlight the need for improved RI performance. The results can help to guide the conduct of future campaigns, improve vaccination monitoring and measles elimination efforts. Moreover, the approaches used here can be readily extended to other countries.

Communicating unexpected and bad news is a stressful yet unavoidable aspect of clinical practice. However, there is a lack of educational models to train clinicians for difficult conversations. This study aims to: describe the main characteristics of the Program to Enhance Relational and Communication Skills (PERCS); present PERCS efficacy at 10 years since its inception in Italy; and illustrate a specific PERCS on organ donation as an example. PERCS is an educational model based on principles of experiential learning, developed at Children's Hospital Boston. PERCS has been offered as a continuing medical education program in an academic hospital in Milan. PERCS workshops last 5 hours and enroll a maximum of 13-15 interdisciplinary participants across levels of experience. The workshops are geared around the simulation and debriefing of difficult conversations. Before and after the workshops, participants rated their perceived preparation, communication and relational skills, confidence, and anxiety on 5-point Likert scales. Pre-post data were analyzed with paired sample t-tests. Between 2008 and 2018, 52 workshops have been offered, involving a total of 602 participants. Participants reported better preparation, confidence, communication and relational skills, and lower anxiety (for all dimensions, p0.001) after the workshops. The strengths of the PERCS model includes: the integration between teaching specific skills and promoting relational attitudes, the learner-centered method, and its efficacy. Major challenges relate to the assessment of actual behavioral change of participants and long-lasting effect of the program at follow-ups.

The aim of the present work is to evaluate the most suitable surgical technique in relation to location and extent of medication-related osteonecrosis of the jaws (MRONJ) through comparison of success rate between the routinely used mucoperiostal flaps and different local flaps designs and propose a standardization of surgical procedures according to MRONJ stage and localization with 2 objectives: to provide the surgeon with an algorithm of treatment according to MRONJ localization and extension; to maximize the success of surgical treatment.Thirteen consecutive patients affected by focal MRONJ were surgically treated with radical osteotomy at the Center for Treatment of the Osteonecrosis of the Jaws (University of Messina, Italy).Initial defects were classified according to the classification of the Italian Societies of Oral Medicine and Maxillofacial Surgery (the SICMF-SIPMO staging system) which consider not only bone exposure but also radiological bone involvement. Treatment outcome was retrospectively assessed according to the different adopted surgical procedure: mucoperiostal flaps (GROUP A) advanced mucoperiostal flaps or rotation flaps (GROUP B) local flaps (GROUP C).Outcome after surgical treatment of focal MRONJ was positive in every group irrespective of MRONJ localization and extension. This may be due to the appropriate selection of surgical procedure.The results obtained demonstrated that focal MRONJ surgical treatment is a reliable procedure irrespective of the initial clinical situation. Radical osteotomy combined with appropriate selection of soft tissue management is crucial.

Introduction Cross Rivers State, in southern Nigeria, conducted measles Supplemental Immunization Activities (SIAs) in 2 phases from 2 -15 March, 2018. The SIAs coordination was led by the State technical coordination committee. A total of 90 supervisors from the national and subnational levels, including consultants were deployed to support the SIAs. The instant messaging service - WhatsApp was utilized to help in the communication and coordination among the State and field teams. Methods We reviewed the chat logs from the WhatsApp group exchanges made between 28 February 2018 and 31 March 2018. Thematic content analysis was done. Results A total of 653 WhatsApp messages were posted among the 55 group members during the study period, including text messages and media content. Eleven percent of the posts related to monitoring processes and data sharing, while posts related to vaccine logistics and waste management made up about 6% of the total. Overall coordination and deployment was covered in 6% of the posts. Forty percent of the media content showed vaccination service delivery and SIAs launching events or monitoring meetings in various areas. The coordination team used WhatsApp to send reminders to the field staff about data sharing, vaccine and waste management, as well as feedback on coverage and completeness of data sharing. The WhatsApp group discussions did not include most of the logistical and hesitancy challenges documented in the State SIAs technical report. Conclusion We recommend focusing group discussions on instant messaging platforms so that they can be used for problem solving and sharing best practices, integrating it with other supervisory processes and tools, as well as providing feedback based on processed data from the field.

The aim of this study is to analyze the clinical outcome and the change in oral-health-related quality of life (QoL) of osteoporotic patients affected by medication-related osteonecrosis of the jaws (MRONJ). Forty-one patients, consecutively treated for a 10-year period, were retrospectively analyzed. All the patients underwent a marginal osseous resective jaw surgery. A clinical 12 months postoperative evaluation has been performed and the complete mucosal healing, the absence of swelling and suppuration, and no signs of disease recurrence were defined like success parameters. Quality-of-life surveys tests like EORTC QQ-C30 and QLQ-HN35 appendices in conjunction with a perceived oral health visual analog scale (VAS) were administered before (time of diagnosis of MRONJ) and after surgery (at least 6 months) in order to record the different oral health status of the treated patients. The majority of MRONJ-diagnosed patients complained symptoms like pain, eating discomfort, and sense problems, with occasional involvement of the social dimension. There was a prevalence of troubles with social eating and social contact.The complete mucosal healing was achieved in 100% of the patients and the administered survey tests reported a significant improvement in all the investigated spheres. Similarly, an increased mean score of perceived oral health VAS was reported.Marginal-resective surgery of the necrotic jaw bone can be an effective treatment of osteoporotic patients affected by localized MRONJ. Quality-of-life parameters are demonstrated to be useful for recording the patient-centered outcome of MRONJ treatment.

BACKGROUND: There are conflicting findings from observational studies of the arrhythrogenic potential of azithromycin. Our aim was to quantify the association between azithromycin use and the risk of ventricular arrhythmia.METHODS: We conducted a nested case-control study within a cohort of new antibiotic users identified from a network of 7 population-based health care databases in Denmark, Germany, Italy, the Netherlands and the United Kingdom for the period 1997-2010. Up to 100 controls per case were selected and matched by age, sex and database. Recency of antibiotic use and type of drug (azithromycin was the exposure of interest) at the index date (occurrence of ventricular arrhythmia) were identified. We estimated the odds of ventricular arrhythmia associated with current azithromycin use relative to current amoxicillin use or nonuse of antibiotics (≥ 365 d without antibiotic exposure) using conditional logistic regression, adjusting for confounders.RESULTS: We identified 14 040 688 new antibiotic users who met the inclusion criteria. Ventricular arrhythmia developed in 12 874, of whom 30 were current azithromycin users. The mean age of the cases and controls was 63 years, and two-thirds were male. In the pooled data analyses across databases, azithromycin use was associated with an increased risk of ventricular arrhythmia relative to nonuse of antibiotics (adjusted odds ratio [OR] 1.97, 95% confidence interval [CI] 1.35-2.86). This increased risk disappeared when current amoxicillin use was the comparator (adjusted OR 0.90, 95% CI 0.48-1.71). Database-specific estimates and meta-analysis confirmed results from the pooled data analysis.INTERPRETATION: Current azithromycin use was associated with an increased risk of ventricular arrhythmia when compared with nonuse of antibiotics, but not when compared with current amoxicillin use. The decreased risk with an active comparator suggests significant confounding by indication.

The study presents a report of 58 metastatic cancer patients who developed osteonecrosis of the jaws after being treated with zoledronic acid and taxanes, plus corticosteroids. A retrospective analysis of data registered in the archives of two Italian osteonecrosis of the jaws treatment centers, who are based at the University of Messina and at the University of Palermo, was performed in order to study, in these patients, demographic data and characteristics such as frequency of cancer location, lines of therapy, frequency of cancer drugs, presence/absence of oral trigger, number, location, and stage of jaw osteonecrosis. It was found that the majority of patients developed advanced stages of osteonecrosis, frequently complicated with infection. It was hypothesized that the concurrent administration of chemotherapeutic agents could be eventually considered as a factor able to allow a faster worsening of the clinical manifestation through the exacerbation of soft tissue defects, due to chemotherapy drugs.

Impairment of the adaptive mechanisms that increase cardiac output during exercise can translate to a reduced functional capacity. We investigated cardiovascular adaptation to exertion in asymptomatic hypertensive patients, aiming to identify the early signs of cardiac and vascular dysfunction.We enrolled 54 subjects: 30 patients (45.1±11.9years, 19 males) and 24 age-matched healthy controls (44.4±9.6years, 14 males). Speckle-tracking echocardiography (STE) and echo-tracking were performed at rest and during exertion to assess myocardial deformation and arterial stiffness.E/E' increased from rest to peak exercise more in patients than in controls (peak stage: p=0.024). Global longitudinal strain increased significantly from rest to peak stage in controls (p=0.011) whereas it remained unchanged in patients (p=0.777). Left atrial (LA) reservoir was significantly increased throughout the exercise only in controls (p=0.001) whereas it was almost unchanged in patients (p=0.293). LA stiffness was significantly higher in patients than in controls both at rest (p=0.023) and during exercise (p0.001). Beta index and pulse wave velocity (PWV) increased during exercise in both groups, showing higher values in patients in each step.Our study showed a more pronounced maladaptation during exercise, with respect to rest, of the cardiovascular system with impaired cardiac-vessel coupling in hypertensive patients compared to healthy subjects. Exercise echocardiography implemented by STE and echo-tracking is invaluable in the early detection of these cardiovascular abnormalities.

Background Measles causes significant childhood morbidity in Nigeria. Routine immunization (RI) coverage is around 40% country-wide, with very high levels of spatial heterogeneity (3–86%), with supplemental immunization activities (SIAs) at 2-year or 3-year intervals. We investigated cost savings and burden reduction that could be achieved by adjusting the inter-campaign interval by region. Methods We modeled 81 scenarios; permuting SIA calendars of every one, two, or three years in each of four regions of Nigeria (North-west, North-central, North-east, and South). We used an agent-based disease transmission model to estimate the number of measles cases and ingredients-based cost models to estimate RI and SIA costs for each scenario over a 10 year period. Results Decreasing SIAs to every three years in the North-central and South (regions of above national-average RI coverage) while increasing to every year in either the North-east or North-west (regions of below national-average RI coverage) would avert measles cases (0.4 or 1.4 million, respectively), and save vaccination costs (save $19.4 or $5.4 million, respectively), compared to a base-case of national SIAs every two years. Decreasing SIA frequency to every three years in the South while increasing to every year in the just the North-west, or in all Northern regions would prevent more cases (2.1 or 5.0 million, respectively), but would increase vaccination costs (add $3.5 million or $34.6 million, respectively), for $1.65 or $6.99 per case averted, respectively. Conclusions Our modeling shows how increasing SIA frequency in Northern regions, where RI is low and birth rates are high, while decreasing frequency in the South of Nigeria would reduce the number of measles cases with relatively little or no increase in vaccination costs. A national vaccination strategy that incorporates regional SIA targeting in contexts with a high level of sub-national variation would lead to improved health outcomes and/or lower costs.

Background Minor salivary gland tumors (MSGTs) are infrequent, representing 10% to 15% of all salivary neoplasms. Despite this low frequency, a significant increase in the incidence of these tumors has been reported in the lasts 30 years. While tumors of the salivary glands can appear at any age, different authors consider the peak of incidence to be associated with old age (60+). The etiopathogenesis of MSGTs remains unclear. In this context, the aim of this study was to explore the hypothesis that age-related changes in salivary antioxidant capacity are involved in the pathogenesis of minor salivary glands tumors to identify possible preventive measures.Furthermore the study aimed to describe the clinico-pathological features of a multi-institutional case series of MSGTs which results are consistent with data in the literature. Methods An electronic search of the English language literature was performed using PubMed and Google scholar ( ). Databases were screened for papers using a number of search strings constructed using relevant terms (minor salivary glands tumors, elderly, diet, antioxidant, saliva, salivary glands). Results According to the world literature, the peak of incidence of MSGTs is between the fifth and seventh decades of life. To date, the only confirmed risk factor for salivary gland tumors is the exposure to ionizing radiation. The significantly reduced salivary antioxidant capacity in old people may explain the higher prevalence of these tumors in the elderly population. Conclusions Further investigation is required to determine the real etiopathogenesis of MSGTs and why these tumors result more frequent in elderly patients.

Antimicrobial resistance (AMR) is one of the biggest issues facing global public health. In 2017, Italy adopted its first National Action Plan on Antimicrobial Resistance 2017&ndash, 2020, which works through the synergy between national, regional, and local levels. In the framework of a Regional Action Plan on healthcare-associated infections and AMR prevention, the Sicilian Health Authority of the Sicilian Region, Southern Italy, has implemented a surveillance system of antibiotic consumption in hospitals, in the community, and of resistance rates (RRs) in hospital settings. Data on antibiotic consumption and on antibiotic RRs have been collected from 2015 to 2017 from pharmacies and laboratories of participating hospitals and from community, respectively. Data on antibiotic consumption showed that the most consumed antibiotics in hospitals were fluoroquinolones in 2015, penicillin in 2016, and beta-lactams in 2017. From 2015 to 2017, data on Klebsiella pneumoniae showed significant increasing RRs to all antibiotic classes, except to carbapenems. RRs of third-generation cephalosporins and carbapenems Escherichia coli showed significant decreasing trends. RRs of the other microorganisms did not change significantly during the study period. The results from the present study show that in Sicily, the use of antibiotics and RRs for selected microorganisms are at a high level. Immediate strategies are needed to decrease the inappropriate usage of antibiotics and control the spread of AMR.