Background
Apical periodontitis (AP) frequently presents as a chronic asymptomatic disease. To arrive at a true diagnosis, in addition to the clinical examination, it is mandatory to undertake ...radiographic examinations such as periapical or panoramic radiographs, or cone‐beam computed tomography (CBCT). Thus, the worldwide burden of AP is probably underestimated or unknown. Previous systematic reviews attempted to estimate the prevalence of AP, but none have investigated which factors may influence its prevalence worldwide.
Objectives
To assess: (i) the prevalence of AP in the population worldwide, as well as the frequency of AP in all teeth, nontreated teeth and root filled teeth; (ii) which factors can modify the prevalence of AP.
Methods
A search was conducted in the PubMed‐MEDLINE, EMBASE, Cochrane‐CENTRAL, LILACS, Google scholar and OpenGrey databases, followed by hand searches, until September 2019. Cross‐sectional, case–control and cohort studies reporting the prevalence of AP in humans, using panoramic or periapical radiograph or CBCT as image methods were included. No language restriction was applied. An adaptation of the Newcastle‐Ottawa Scale was used to evaluate the quality of the studies. A meta‐analysis was performed to determine the pooled prevalence of AP at the individual level. Secondary outcomes were the frequency of AP in all teeth, nontreated teeth and rootfilled teeth. Subgroup analyses using random‐effect models were carried out to analyse the influence of explanatory covariables on the outcome.
Results
The search strategy identified 6670 articles, and 114 studies were included in the meta‐analysis, providing data from 34 668 individuals and 639 357 teeth. The prevalence of AP was 52% at the individual level (95% CI 42%–56%, I2 = 97.8%) and 5% at the tooth level (95% CI 4%–6%; I2 = 99.5%). The frequency of AP in root‐filled teeth and nontreated teeth was 39% (95% CI 36%–43%; I2 = 98.5%) and 3% (95% CI 2%–3%; I2 = 99.3%), respectively. The prevalence of AP was greater in samples from dental care services (DCS; 57%; 95% CI 52%–62%; I2 = 97.8%) and hospitals (51%; 95% CI 40%–63%; I2 = 95.9%) than in those from the general population (GP; 40%; 95% CI 33%–46%; I2 = 96.5%); it was also greater in people with a systemic condition (63%; 95% CI 56%–69%, I2 = 89.7%) compared to healthy individuals (48%; 95% CI 43%–53%; I2 = 98.3%).
Discussion
The subgroup analyses identified explanatory factors related to the variability in the prevalence of AP. However, the high clinical heterogeneity and high risk of bias across the primary studies indicate that the findings must be interpreted with caution.
Conclusions
Half of the adult population worldwide have at least one tooth with apical periodontitis. The prevalence of AP is greater in samples from the dental care services, but it is also high amongst community representative samples from the general population. The present findings should bring the attention of health policymakers, medical and dental communities to the hidden burden of endodontic disease in the population worldwide.
Cholangiocarcinoma (CCA) includes a cluster of highly heterogeneous biliary malignant tumours that can arise at any point of the biliary tree. Their incidence is increasing globally, currently ...accounting for ~15% of all primary liver cancers and ~3% of gastrointestinal malignancies. The silent presentation of these tumours combined with their highly aggressive nature and refractoriness to chemotherapy contribute to their alarming mortality, representing ~2% of all cancer-related deaths worldwide yearly. The current diagnosis of CCA by non-invasive approaches is not accurate enough, and histological confirmation is necessary. Furthermore, the high heterogeneity of CCAs at the genomic, epigenetic and molecular levels severely compromises the efficacy of the available therapies. In the past decade, increasing efforts have been made to understand the complexity of these tumours and to develop new diagnostic tools and therapies that might help to improve patient outcomes. In this expert Consensus Statement, which is endorsed by the European Network for the Study of Cholangiocarcinoma, we aim to summarize and critically discuss the latest advances in CCA, mostly focusing on classification, cells of origin, genetic and epigenetic abnormalities, molecular alterations, biomarker discovery and treatments. Furthermore, the horizon of CCA for the next decade from 2020 onwards is highlighted.
The family of bile acids includes a group of molecular species of acidic steroids with very peculiar physicalchemical and biological characteristics. They are synthesized by the liver from ...cholesterol through several complementary pathways that are controlled by mechanisms involving fine-tuning by the levels of certain bile acid species. Although their best- known role is their participation in the digestion and absorption of fat, they also play an important role in several other physiological processes. Thus, genetic abnormalities accounting for alterations in their synthesis, biotransformation and/or transport may result in severe alterations, even leading to lethal situations for which the sole therapeutic option may be liver transplantation. Moreover, the increased levels of bile acids reached during cholestatic liver diseases are known to induce oxidative stress and apoptosis, resulting in damage to the liver parenchyma and, eventually, extrahepatic tissues. When this occurs during pregnancy, the outcome of gestation may be challenged. In contrast, the physical-chemical and biological properties of these compounds have been used as the bases for the development of drugs and as pharmaceutical tools for the delivery of active agents.
Traditional Chinese medicine commands a unique position among all traditional medicines because of its 5000 years of history. Our own interest in natural products from traditional Chinese medicine ...was triggered in the 1990s, by artemisinin-type sesquiterpene lactones from Artemisia annua L. As demonstrated in recent years, this class of compounds has activity against malaria, cancer cells, and schistosomiasis. Interestingly, the bioactivity of artemisinin and its semisynthetic derivative artesunate is even broader and includes the inhibition of certain viruses, such as human cytomegalovirus and other members of the Herpesviridae family (e.g., herpes simplex virus type 1 and Epstein-Barr virus), hepatitis B virus, hepatitis C virus, and bovine viral diarrhea virus. Analysis of the complete profile of the pharmacological activities and molecular modes of action of artemisinin and artesunate and their performance in clinical trials will further elucidate the full antimicrobial potential of these versatile pharmacological tools from nature.
In this paper, we present a method for simultaneously tracking thousands of targets in biological image sequences, which is of major importance in modern biology. The complexity and inherent ...randomness of the problem lead us to propose a unified probabilistic framework for tracking biological particles in microscope images. The framework includes realistic models of particle motion and existence and of fluorescence image features. For the track extraction process per se, the very cluttered conditions motivate the adoption of a multiframe approach that enforces tracking decision robustness to poor imaging conditions and to random target movements. We tackle the large-scale nature of the problem by adapting the multiple hypothesis tracking algorithm to the proposed framework, resulting in a method with a favorable tradeoff between the model complexity and the computational cost of the tracking procedure. When compared to the state-of-the-art tracking techniques for bioimaging, the proposed algorithm is shown to be the only method providing high-quality results despite the critically poor imaging conditions and the dense target presence. We thus demonstrate the benefits of advanced Bayesian tracking techniques for the accurate computational modeling of dynamical biological processes, which is promising for further developments in this domain.
The 6-min walk distance (6MWD) predicted values have been derived from small cohorts mostly from single countries. The aim of the present study was to investigate differences between countries and ...identify new reference values to improve 6MWD interpretation. We studied 444 subjects (238 males) from seven countries (10 centres) ranging 40-80 yrs of age. We measured 6MWD, height, weight, spirometry, heart rate (HR), maximum HR (HR(max)) during the 6-min walk test/the predicted maximum HR (HR(max) % pred), Borg dyspnoea score and oxygen saturation. The mean ± sd 6MWD was 571 ± 90 m (range 380-782 m). Males walked 30 m more than females (p < 0.001). A multiple regression model for the 6MWD included age, sex, height, weight and HR(max) % pred (adjusted r² = 0.38; p < 0.001), but there was variability across centres (adjusted r² = 0.09-0.73) and its routine use is not recommended. Age had a great impact in 6MWD independent of the centres, declining significantly in the older population (p < 0.001). Age-specific reference standards of 6MWD were constructed for male and female adults. In healthy subjects, there were geographic variations in 6MWD and caution must be taken when using existing predictive equations. The present study provides new 6MWD standard curves that could be useful in the care of adult patients with chronic diseases.
Objective
To assess the association and magnitude of the effect of early exposure to different types of interpersonal violence (IPV) with suicide attempt and suicide death in youths and young adults.
...Method
We searched six databases until June 2015. Inclusion criteria were as follows: (1) assessment of any type of IPV as risk factor of suicide attempt or suicide: (i) child maltreatment childhood physical, sexual, emotional abuse, neglect, (ii) bullying, (iii) dating violence, and (iv) community violence; (2) population‐based case–control or cohort studies; and (3) subjects aged 12–26 years. Random models were used for meta‐analyses (Reg: CRD42013005775).
Results
From 23 682 articles, 29 articles with 143 730 subjects for meta‐analyses were included. For victims of any IPV, OR of subsequent suicide attempt was 1.99 (95% CI: 1.73–2.28); for child maltreatment, 2.25 (95% CI: 1.85–2.73); for bullying, 2.39 (95% CI: 1.89–3.01); for dating violence, 1.65 (95% CI: 1.40–1.94); and for community violence, 1.48 (95% CI: 1.16–1.87). Young victims of IPV had an OR of suicide death of 10.57 (95% CI: 4.46–25.07).
Conclusion
Early exposure to IPV confers a risk of suicide attempts and particularly suicide death in youths and young adults. Future research should address the effectiveness of preventing and detecting early any type of IPV exposure in early ages.
IMPORTANCE The current recommendation is for at least 12 months of dual antiplatelet therapy after implantation of a drug-eluting stent. However, the optimal duration of dual antiplatelet therapy ...with specific types of drug-eluting stents remains unknown. OBJECTIVE To assess the clinical noninferiority of 3 months (short-term) vs 12 months (long-term) of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) with zotarolimus-eluting stents. DESIGN, SETTING, AND PATIENTS The OPTIMIZE trial was an open-label, active-controlled, 1:1 randomized noninferiority study including 3119 patients in 33 sites in Brazil between April 2010 and March 2012. Clinical follow-up was performed at 1, 3, 6, and 12 months. Eligible patients were those with stable coronary artery disease or history of low-risk acute coronary syndrome (ACS) undergoing PCI with zotarolimus-eluting stents. INTERVENTIONS After PCI with zotarolimus-eluting stents, patients were prescribed aspirin (100-200 mg daily) and clopidogrel (75 mg daily) for 3 months (n = 1563) or 12 months (n = 1556), unless contraindicated because of occurrence of an end point. MAIN OUTCOMES AND MEASURES The primary end point was net adverse clinical and cerebral events (NACCE; a composite of all-cause death, myocardial infarction MI, stroke, or major bleeding); the expected event rate at 1 year was 9%, with a noninferiority margin of 2.7%. Secondary end points were major adverse cardiac events (MACE; a composite of all-cause death, MI, emergent coronary artery bypass graft surgery, or target lesion revascularization) and Academic Research Consortium definite or probable stent thrombosis. RESULTS NACCE occurred in 93 patients receiving short-term and 90 patients receiving long-term therapy (6.0% vs 5.8%, respectively; risk difference, 0.17 95% CI, −1.52 to 1.86; P = .002 for noninferiority). Kaplan-Meier estimates demonstrated MACE rates at 1 year of 8.3% (128) in the short-term group and 7.4% (114) in the long-term group (HR, 1.12 95% CI, 0.87-1.45). Between 91 and 360 days, no statistically significant association was observed for NACCE (39 2.6% vs 38 2.6% for the short- and long-term groups, respectively; HR, 1.03 95% CI, 0.66-1.60), MACE (78 5.3% vs 64 4.3%; HR, 1.22 95% CI, 0.88-1.70), or stent thrombosis (4 0.3% vs 1 0.1%; HR, 3.97 95% CI, 0.44-35.49). CONCLUSIONS AND RELEVANCE In patients with stable coronary artery disease or low-risk ACS treated with zotarolimus-eluting stents, 3 months of dual antiplatelet therapy was noninferior to 12 months for NACCE, without significantly increasing the risk of stent thrombosis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01113372
Although surgical resection is the standard curative therapy for gastric cancer, these tumors are often diagnosed at an advanced stage, when surgery is not recommended. Alternative treatments such as ...radiotherapy and chemotherapy achieve only very modest results. There is therefore an urgent need to advance in this field of oncologic gastroenterology. The poor response of gastric cancer to chemotherapy is usually due to a combination of mechanisms of chemoresistance (MOC), which may include a reduction in drug uptake (MOC-1a), enhanced drug efflux (MOC-1b), a reduced proportion of active agents in tumor cells due to a reduction in pro-drug activation or an enhancement in drug inactivation (MOC-2), changes in the expression/function of the molecular targets of anticancer drugs (MOC-3), an enhanced ability of cancer cells to repair anticancer drug-induced DNA damage (MOC-4), and decreased expression/function of pro-apoptotic factors or up-regulation of anti-apoptotic genes (MOC-5). Two major goals of modern pharmacology aimed at overcoming this situation are the prediction of a lack of response to chemotherapy and the identification of the underlying mechanisms accounting for primary or acquired refractoriness to anticancer drugs. These are important issues if we are to select the best pharmacological regime for each patient and develop novel strategies to overcome chemoresistance. The present review reports updated information regarding the mechanisms of chemoresistance (from MOC-1 to MOC-5) in gastric cancer, the advances made in the prediction of the failure of chemotherapeutic treatment, and novel strategies based on gene therapy currently being developed to treat these tumors.
Biliary tract cancers (BTCs) are a group of rare and aggressive malignancies that arise in the biliary tree within and outside the liver. Beyond surgical resection, which is beneficial for only a ...small proportion of patients, current strategies for treating patients with BTCs include chemotherapy, as a single agent or combination regimens, in the adjuvant and palliative setting. Increased characterisation of the molecular landscape of these tumours has facilitated the identification of molecular vulnerabilities, such as IDH mutations and FGFR fusions, that can be exploited for the treatment of BTC patients. Beyond targeted therapies, active research avenues explore the development of novel therapeutics that target the crosstalk between cancer and stroma, the cellular pathways involved in the regulation of cell death, the chemoresistance phenotype and the dysregulation of RNA. In this review, we discuss the therapeutic opportunities currently available in the management of BTC patients, and explore the strategies that can support the implementation of precision oncology in BTCs, including novel molecular targets, liquid biopsies and patient-derived predictive tools.
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