Once-Weekly Dulaglutide for the Treatment of Youths with Type 2 Diabetes.

BACKGROUND: The incidence of type 2 diabetes mellitus is increasing among youths. Once-weekly treatment with dulaglutide, a glucagon-like peptide-1 receptor agonist, may have efficacy with regard to glycemic control in youths with type 2 diabetes. METHODS: In a double-blind, placebo-controlled, 26-week trial, we randomly assigned participants (10 to <18 years of age; body-mass index [BMI], >85th percentile) being treated with lifestyle modifications alone or with metformin, with or without basal insulin, in a 1:1:1 ratio to receive once-weekly subcutaneous injections of placebo, dulaglutide at a dose of 0.75 mg, or dulaglutide at a dose of 1.5 mg. Participants were then included in a 26-week open-label extension study in which those who had received placebo began receiving dulaglutide at a weekly dose of 0.75 mg. The primary end point was the change from baseline in the glycated hemoglobin level at 26 weeks. Secondary end points included a glycated hemoglobin level of less than 7.0% and changes from baseline in the fasting glucose concentration and BMI. Safety was also assessed. RESULTS: A total of 154 participants underwent randomization. At 26 weeks, the mean glycated hemoglobin level had increased in the placebo group (0.6 percentage points) and had decreased in the dulaglutide groups (-0.6 percentage points in the 0.75-mg group and -0.9 percentage points in the 1.5-mg group, P<0.001 for both comparisons vs. placebo). At 26 weeks, a higher percentage of participants in the pooled dulaglutide groups than in the placebo group had a glycated hemoglobin level of less than 7.0% (51% vs. 14%, P<0.001). The fasting glucose concentration increased in the placebo group (17.1 mg per deciliter) and decreased in the pooled dulaglutide groups (-18.9 mg per deciliter, P<0.001), and there were no between-group differences in the change in BMI. The incidence of gastrointestinal adverse events was higher with dulaglutide therapy than with placebo. The safety profile of dulaglutide was consistent with that reported in adults. CONCLUSIONS: Treatment with dulaglutide at a once-weekly dose of 0.75 mg or 1.5 mg was superior to placebo in improving glycemic control through 26 weeks among youths with type 2 diabetes who were being treated with or without metformin or basal insulin, without an effect on BMI. (Funded by Eli Lilly; AWARD-PEDS ClinicalTrials.gov number, NCT02963766.).

Estimating insulin sensitivity and ß-cell function from the oral glucose tolerance test: validation of a new insulin sensitivity and secretion (ISS) model.

Efficient and accurate methods to estimate insulin sensitivity (SI) and ß-cell function (BCF) are of great importance for studying the pathogenesis and treatment effectiveness of type 2 diabetes (T2D). Existing methods range in sensitivity, input data, and technical requirements. Oral glucose tolerance tests (OGTTs) are preferred because they are simpler and more physiological than intravenous methods. However, current analytical methods for OGTT-derived SI and BCF also range in complexity; the oral minimal models require mathematical expertise for deconvolution and fitting differential equations, and simple algebraic surrogate indices (e.g., Matsuda index, insulinogenic index) may produce unphysiological values. We developed a new insulin secretion and sensitivity (ISS) model for clinical research that provides precise and accurate estimates of SI and BCF from a standard OGTT, focusing on effectiveness, ease of implementation, and pragmatism. This model was developed by fitting a pair of differential equations to glucose and insulin without need of deconvolution or C-peptide data. This model is derived from a published model for longitudinal simulation of T2D progression that represents glucose-insulin homeostasis, including postchallenge suppression of hepatic glucose production and first- and second-phase insulin secretion. The ISS model was evaluated in three diverse cohorts across the lifespan. The new model had a strong correlation with gold-standard estimates from intravenous glucose tolerance tests and insulin clamps. The ISS model has broad applicability among diverse populations because it balances performance, fidelity, and complexity to provide a reliable phenotype of T2D risk.NEW & NOTEWORTHY The pathogenesis of type 2 diabetes (T2D) is determined by a balance between insulin sensitivity (SI) and ß-cell function (BCF), which can be determined by gold standard direct measurements or estimated by fitting differential equation models to oral glucose tolerance tests (OGTTs). We propose and validate a new differential equation model that is simpler to use than current models and requires less data while maintaining good correlation and agreement with gold standards. Matlab and Python code is freely available.

ALS-associated VRK1 R321C mutation causes proteostatic imbalance and mitochondrial defects in iPSC-derived motor neurons.

Vaccinia-related kinase 1 (VRK1) is a gene which has been implicated in the pathological process of a broad range of neurodevelopmental disorders as well as neuropathies, such as Amyotrophic Lateral Sclerosis (ALS). Here we report a family presenting ALS in an autosomal recessive mode of inheritance, segregating with a homozygous missense mutation located in VRK1 gene (p.R321C; Arg321Cys). Proteomic analyses from iPSC-derived motor neurons identified 720 proteins eligible for subsequent investigation, and our exploration of protein profiles revealed significant enrichments in pathways such as mTOR signaling, E2F, MYC targets, DNA repair response, cell proliferation and energetic metabolism. Functional studies further validated such alterations, showing that affected motor neurons presented decreased levels of global protein output, ER stress and downregulation of mTOR signaling. Mitochondrial alterations also pointed to decreased reserve capacity and increased non-mitochondrial oxygen consumption. Taken together, our results present the main pathological alterations associated with VRK1 mutation in ALS.

Behind Prep Decisions: Understanding User Patterns and Discontinuation Factors in Real-World.

This study aimed to characterize the epidemiological aspects of PrEP use and barriers to accessing this prophylaxis. This cross-sectional study was conducted between January 2021 and April 2022, encompassing 140 PrEP users treated at the Testing and Counseling Center (CTA) in Campo Grande, Mato Grosso do Sul. Data on sociodemographic characteristics and factors associated with PrEP discontinuation were obtained using a standardized questionnaire. Most PrEP users were cisgender men (92.00%), predominantly white (51.00%), over 30 years of age (56.50%), homosexual-oriented (76.50%), and had a minimum of 12 years of education (77.50%). Approximately 60.00% admitted to inconsistent condom use in recent sexual encounters, primarily involving anal intercourse. Approximately 88.00% perceived themselves as at risk of contracting STIs in the upcoming year. Regarding new presentation forms, 54.00% indicated a willingness to use "on-demand PrEP," and 92.00% expressed interest in using "injectable PrEP." After 6 months of follow-up, 43.60% (95.00% CI: 35.50-52.00) discontinued PrEP use, primarily due to changes in sexual behavior (38.30%) and difficulties accessing healthcare services (21.28%). This study underscores the need to involve diverse key populations and highlights the significance of PrEP as an ongoing monitoring strategy for HIV/STI prevention in addition to the importance of incorporating new formulations such as daily oral PrEP into the Brazilian National Health System (SUS).

Composition and optical properties of (In, Ga)As nanowires grown by group-III-assisted molecular beam epitaxy.

(In, Ga) alloy droplets are used to catalyse the growth of (In, Ga)As nanowires by molecular beam epitaxy on Si(111) substrates. The composition, morphology and optical properties of these nanowires can be tuned by the employed elemental fluxes. To incorporate more than 10% of In, a high In/(In+Ga) flux ratio above 0.7 is required. We report a maximum In content of almost 30% in bulk (In, Ga)As nanowires for an In/(In+Ga) flux ratio of 0.8. However, with increasing In/(In+Ga) flux ratio, the nanowire length and diameter are notably reduced. Using photoluminescence and cathodoluminescence spectroscopy on nanowires covered by a passivating (In, Al)As shell, two luminescence bands are observed. A significant segment of the nanowires shows homogeneous emission, with a wavelength corresponding to the In content in this segment, while the consumption of the catalyst droplet leads to a spectrally-shifted emission band at the top of the nanowires. The (In,Ga)As nanowires studied in this work provide a new approach for the integration of infrared emitters on Si platforms.

Early morphological and neurochemical changes of the bed nucleus of stria terminalis (BNST) in gestational protein-restricted male offspring.

BACKGROUND: The bed nucleus of the stria terminalis (BNST) is a structure with a peculiar neurochemical composition involved in modulating anxietylike behavior and fear. AIM: The present study investigated the effects on the BNST neurochemical composition and neuronal structure in critical moments of the postnatal period in gestational protein-restricted male rats' offspring. METHODS: Dams were maintained during the pregnancy on isocaloric rodent laboratory chow with standard protein content [NP, 17%] or low protein content [LP, 6%]. BNST from male NP and age-matched LP offspring was studied using the isotropic fractionator method, Neuronal 3D reconstruction, dendritic-tree analysis, blotting analysis, and high-performance liquid chromatography. RESULTS: Serum corticosterone levels were higher in male LP offspring than NP rats in 14-day-old offspring, without any difference in 7-day-old progeny. The BNST total cell number and anterodorsal BNST division volume in LP progeny were significantly reduced on the 14th postnatal day compared with NP offspring. The BNST HPLC analysis from 7 days-old LP revealed increased norepinephrine levels compared to NP progeny. The BNST blot analysis from 7-day-old LP revealed reduced levels of GR and BDNF associated with enhanced CRF1 expression compared to NP offspring. 14-day-old LP offspring showed reduced expression of MR and 5HT1A associated with decreased DOPAC and DOPA turnover levels relative to NP rats. In Conclusion, the BNST cellular and neurochemical changes may represent adaptation during development in response to elevated fetal exposure to maternal corticosteroid levels. In this way, gestational malnutrition alters the BNST content and structure and contributes to already-known behavioral changes.

Triheptanoin, an odd-medium-chain triglyceride, impacts brain cognitive function in young and aged mice.

ABSTRACTThe brain aging process triggers cognitive function impairment, such as memory loss and compromised quality of life. Cognitive impairment is based on bioenergetic status, with reduced glucose uptake and metabolism in aged brains. Anaplerotic substrates are reported to promote mitochondrial ATP generation, having been tested in clinical trials for the treatment of neurological disorders and metabolic diseases.Objectives and Methods: To assess whether the improvement in oxidative capacity ameliorates cognitive function in adults (12 weeks), and aged (22-month-old) C57/6BJ mice, they received (1) a ketogenic diet, (2) a ketogenic diet supplemented with the anaplerotic substance, triheptanoin, or (3) a control diet for 12 weeks. Spontaneous alternation and time spent in a previously closed arm in the Y-maze test and time interacting with an unknown object in the novel object recognition test (NORT) were used to evaluate working memory. Acetylcholinesterase (AChE) activity in the prefrontal lobe, brain left hemisphere, and cerebellum was also evaluated. Glucose transporter 3 (GLUT3) expression in the prefrontal lobe was analyzed by western blotting.Results: The ketogenic diet (KD) reduced spontaneous alternation in aged mice, leading to lower AChE activity in the aged prefrontal lobe and cerebellum, and in the parieto-temporal-occipital lobe of adult mice. Furthermore, KD decreased GLUT3 protein expression in the frontal lobe of the adults.Discussion: Supplementation of KD with triheptanoin prevented memory impairment and showed similar values of AChE activity and GLUT3 expression compared to the controls. Our data suggest that triheptanoin has a potential role in the bioenergetic capacity of the brain, improving cognitive function.

Association of tyrosine hydroxylase 01 (TH01) microsatellite and insulin gene (INS) variable number of tandem repeat (VNTR) with type 2 diabetes and fasting insulin secretion in Mexican population.

PURPOSE: A variable number of tandem repeats (VNTR) in the insulin gene (INS) control region may be involved in type 2 diabetes (T2D). The TH01 microsatellite is near INS and may regulate it. We investigated whether the TH01 microsatellite and INS VNTR, assessed via the surrogate marker single nucleotide polymorphism rs689, are associated with T2D and serum insulin levels in a Mexican population. METHODS: We analyzed a main case-control study (n = 1986) that used univariate and multivariate logistic regression models to calculate the risk conferred by TH01 and rs689 loci for T2D development; rs689 results were replicated in other case-control (n = 1188) and cross-sectional (n = 1914) studies. RESULTS: TH01 alleles 6, 8, 9, and 9.3 and allele A of rs689 were independently associated with T2D, with differences between sex and age at diagnosis. TH01 alleles with ≥ 8 repeats conferred an increased risk for T2D in males compared with ≤ 7 repeats (odds ratio, ≥ 1.46; 95% confidence interval, 1.1-1.95). In females, larger alleles conferred a 1.5-fold higher risk for T2D when diagnosed ≥ 46 years but conferred protection when diagnosed ≤ 45 years. Similarly, rs689 allele A was associated with T2D in these groups. In males, larger TH01 alleles and the rs689 A allele were associated with a significant decrease in median fasting plasma insulin concentration with age in T2D cases; the reverse occurred in controls. CONCLUSION: Larger TH01 alleles and rs689 A allele may potentiate insulin synthesis in males without T2D, a process disabled in those with T2D.

Rupture of a flow aneurysm secondary to spontaneous extracranial to intracranial revascularisation in the posterior fossa following radiation-induced vasculopathy for cerebellar tumour.

Paediatric patients receiving cranial irradiation therapy for brain tumours are at increased risk of cerebrovascular complications. Radiation-induced moyamoya syndrome (MMS) is a well-recognised complication of this. We present a case of an 8-year-old boy with a history of medulloblastoma, who underwent surgical excision followed by post-operative adjuvant oncological treatment. Six years later, he developed cerebellar/intraventricular haemorrhage. He underwent an emergency external ventricular drain (EVD) insertion followed by posterior fossa suboccipital craniotomy. On dural opening, an abnormal vessel was visualised on the surface of the right cerebellar hemisphere, which was not disturbed. No obvious abnormalities were identified intra-operatively. Cerebral catheter angiography confirmed the presence of a right-sided occipital artery (OA) to posterior inferior cerebellar artery (PICA) extracranial to intracranial (EC-IC) bypass with a zone of the distal PICA territory supplied by this EC-IC bypass. A presumed flow aneurysm originated from the bypass in the distal PICA, identified as cause for the haemorrhage. We highlight a rare cause for intracranial haemorrhage in this cohort of patients. Children who have undergone radiotherapy may have exquisitely sensitive cerebral vasculature and need careful vigilance and evaluation for vasculopathic complications following spontaneous haemorrhage.

Beneficial and harmful effects of physical activity on care-seeking for low back pain: the AUTBACK study.

PURPOSE: People who seek more care for low back pain (LBP) tend to experience poorer recovery (e.g. higher pain and disability levels). Understanding the factors associated with care-seeking for LBP might improve patient outcomes and potentially alleviate the burden of LBP on global health systems. This study aimed to investigate the relationship between different intensities, volumes, and domains of physical activity and care-seeking behaviours, in people with a history of LBP. METHODS: Longitudinal data from adult twins were drawn from the AUstralian Twin BACK study. The primary outcome was the total self-reported frequency (counts) of overall utilisation of care for LBP, over 1 year. Secondary outcomes were the utilisation of health services, and the utilisation of self-management strategies, for LBP (assessed as total frequency over 1 year). Explanatory variables were device-based measures of sedentary behaviour and moderate-to-vigorous intensity physical activity, and self-reported physical workload, and work, transport, household, and leisure domain physical activity, at baseline. RESULTS: Data from 340 individuals were included. Median age was 56.4 years (IQR 44.9-62.3 years) and 73% of participants were female. Medium-to-high baseline volumes of sedentary behaviour were significantly associated with greater counts of overall care utilisation (IRR 1.60, 95%CI 1.04-2.44) and utilisation of self-management strategies (IRR 1.60, 95%CI 1.02-2.50) for LBP, over 1 year. Medium-to-high baseline volumes of household domain physical activity were significantly associated with greater counts of utilising self-management strategies for LBP over 1 year (IRR 1.62, 95%CI 1.04-2.53). No explanatory variables were associated with the utilisation of health services for LBP. CONCLUSION: People who engage in higher baseline volumes of sedentary behaviour or physical activity in the household setting (e.g. housework, gardening, yard work, general household maintenance) utilise 1.6 times more care for LBP over 1 year. Findings suggest that higher volumes of these behaviours may be harmful for LBP. No intensities, volumes, or domains of physical activity demonstrated clear benefits for LBP. Where feasible, patients and clinicians should collaborate to screen and develop strategies to reduce engagement in sedentary behaviour or physical activity in the household setting. Contextual factors (e.g. patient symptom severity, sociocultural roles, occupational demands) should be considered when devising appropriate behaviour change strategies.

Unknown parent groups and truncated pedigree in single-step genomic evaluations of Murrah buffaloes.

Missing pedigrees may produce bias in genomic evaluations. Thus, strategies to deal with this problem have been proposed as using unknown parent groups (UPG) or truncated pedigrees. The aim of this study was to investigate the impact of modeling missing pedigrees under single-step genomic best linear unbiased prediction (ssGBLUP) evaluations for productive and reproductive traits in dairy buffalo using different approaches: (1) traditional BLUP without UPG (BLUP), (2) traditional BLUP including UPG (BLUP/UPG), (3) ssGBLUP without UPG (ssGBLUP), (4) ssGBLUP including UPG in the A and A22 matrices (ssGBLUP/A_UPG), (5) ssGBLUP including UPG in all elements of the H matrix (ssGBLUP/H_UPG), (6) BLUP with pedigree truncation for the last 3 generations (BLUP/truncated), and (7) ssGBLUP with pedigree truncation for the last 3 generations (ssGBLUP/truncated). Unknown parent groups were not used in the scenarios with truncated pedigree. A total of 3,717, 4,126, and 3,823 records of the first lactation for accumulated 305-d milk yield (MY), age at first calving (AFC), and lactation length (LL), respectively, were used. Accuracies ranged from 0.27 for LL (BLUP) to 0.46 for MY (BLUP), bias ranged from -0.62 for MY (ssGBLUP) to 0.0002 for AFC (BLUP/truncated), and dispersion ranged from 0.88 for MY (BLUP/A_UPG) to 1.13 for LL (BLUP). Genetic trend showed genetic gains for all traits across 20 years of selection, and the impact of including genomic information, UPG, or pedigree truncation under GEBV accuracies ranged among the evaluated traits. Overall, methods using UPG, truncation pedigree, and genomic information exhibited potential to improve GEBV accuracies, bias, and dispersion for all traits compared with other methods. Truncated scenarios promoted high genetic gains. In small populations with few genotyped animals, combining truncated pedigree or UPG with genomic information is a feasible approach to deal with missing pedigrees.

Feeding practices and dietary intake in Brazilian children with Down syndrome: A cross-sectional study.

BACKGROUND: Studies investigating the quality of the diet and dietary intake of children with Down syndrome (DS) are required because the features attributed to the syndrome can affect growth, development and quality of life. METHODS: This cross-sectional study was conducted with 77 Brazilian children with DS between 5 and 36 months of age receiving care at the multidisciplinary outpatient clinic of the University Hospital. Participants' sociodemographic, dietary and anthropometric data were collected from the care protocols. Dietary data were collected from 24-h recalls and dietary practices were assessed according to the WHO dietary guidelines. Associations between inadequate feeding practices and demographic variables were assessed using logistic regression models. RESULTS: Fruits, milk or infant formula, vegetables, beans and meat were among the five most consumed foods by the children investigated. Overall, we observed a high number of cases of early weaning (50.6%), low minimum dietary diversity (MDD; 40.3%), inadequate consistency for age (64.9%), early presence of ultra-processed foods (76.6%), sugars and sweets (33.8%) in the diet of the children with DS. In the associations of inadequate feeding practices by age group, low MDD [odds ratio (OR): 18.6; 95% confidence interval (CI): 3.4; 57.1] and inadequate consistency (OR: 6.65; 95% CI: 1.8; 24.7) were more frequent among children aged below 12 months while this relationship was inverse for early introduction of sugar and sweets (OR: 0.04; 95% CI: 0.01; 0.29). CONCLUSION: Our findings showed a high number of cases of inadequate dietary practices in children with DS investigated, which could adversely affect the long-term health of this population.

Evaluating the cognitive effects of interventions to reduce social isolation and loneliness in older adults: a systematic review.

OBJECTIVES: Social isolation and loneliness among older adults present serious public health challenges linked to increased dementia risk. This systematic review analyzes interventions addressing social isolation and loneliness in older adults and their cognitive effects to inform future dementia prevention programs. METHOD: We systematically searched databases (PUBMED, PsycINFO, SCOPUS, EBSCO, and SAGE Journals) from February to May 2023 and updated from August to November 2023 using terms like social isolation, loneliness, intervention, and cognitive outcome. We included studies that assessed cognitive outcomes (such as global cognition or specific domains) and non-cognitive outcomes (including depression, well-being, and functionality). Study quality was assessed using Cochrane's RoB 2, ROBINS-I, and other appraisal tools, with results synthesized narratively. RESULTS: Nine studies (1025 participants) were included, with a high risk of bias in most randomized trials (except one) and a low-to-moderate risk in non-randomized studies. Six studies showed improved cognitive function post-intervention, five of which involved technology. Two studies demonstrated reduced loneliness and improved cognition. CONCLUSION: Technological interventions promise to reduce social isolation and loneliness, positively impacting cognitive function. Despite this, these interventions did not directly impact social isolation, which requires future and larger studies to understand more in-depth the role of these approaches for individuals with social isolation. The interventions promoting social interactions could lead to higher social identification, well-being, and interest in life. Multidomain interventions, including technology, are effective. Limitations include study scarcity and heterogeneity, highlighting the need for more robust research on interventions to alleviate social isolation and loneliness and enhance cognitive function.Systematic Review Registration PROSPERO CRD42023460933.

Severity of papular urticaria in children is associated with specific IgG4 anti-salivary gland antigens from Aedes aegypti.

Summary: Background. Papular Urticaria (PU) is a cutaneous hypersensitivity disorder triggered by hematophagous arthropod bites. Despite being a common condition, especially in tropical environments, many knowledge gaps are observed for this disease. The main objective of this study was to investigate the patterns of humoral immune response to mosquito antigens in children with PU and establish a correlation between this response and the severity of clinical symptoms. Methods. An analytical cross-sectional observational study was carried out. Clinical and sociodemographic data and children's blood samples were collected to measure the specific antibodies from: 1. A. aegypti salivary gland antigens; 2. A. aegypti whole body antigens (both produced in the laboratory of the Center for Health Sciences at the Federal University of Rio de Janeiro). A PU severity score based on clinical data is proposed to correlate disease severity with antibody reactivity signatures. Results. According to the clinical data, 58.9% of children received high severity scores. A significant statistical correlation was found between patients with high PU severity score and the development of symptoms before the age of two (p = 0.0326) and high IgG4 anti-salivary gland antigens concentration (p less than 0.05). Conclusion. It is suggested that PU severity in children is associated with a high concentration of IgG4 anti-salivary gland antigens from Aedes aegypti. Further studies are recommended to deepen the understanding of the mechanisms involved.

UAV-UGV Collaborative Localisation with Minimum Sensing.

This paper presents a novel methodology to localise Unmanned Ground Vehicles (UGVs) using Unmanned Aerial Vehicles (UAVs). The UGVs are assumed to be operating in a Global Navigation Satellite System (GNSS)-denied environment. The localisation of the ground vehicles is achieved using UAVs that have full access to the GNSS. The UAVs use range sensors to localise the UGV. One of the major requirements is to use the minimum number of UAVs, which is two UAVs in this paper. Using only two UAVs leads to a significant complication that results an estimation unobservability under certain circumstances. As a solution to the unobservability problem, the main contribution of this paper is to present a methodology to treat the unobservability problem. A Constrained Extended Kalman Filter (CEKF)-based solution, which uses novel kinematics and heuristics-based constraints, is presented. The proposed methodology has been assessed based on the stochastic observability using the Posterior Cramér-Rao Bound (PCRB), and the results demonstrate the successful operation of the proposed localisation method.

Analysis of scientific publications on oral cancer diagnosis delays: a bibliometric study over 22 years.

BACKGROUND: The area of oncology still lacks bibliometric studies that investigate the diagnostic interval of oral cancer. This study proposed to carry out a bibliometric analysis of epidemiological studies that investigated the diagnosis of oral cancer between 2002 to 2024. MATERIAL AND METHODS: On April, 2024, the Scopus and Web of Science databases were explored, and the selected articles underwent bibliometric analysis of performance and scientific mapping of journals, authors, institutions, and countries, as well as the predominant topics and trends in research into the diagnosis of oral cancer through an analysis of references and co-occurrence of key words. The analyzes were carried out using the R extension package, Bibliometrix, and the VOSviewer software. RESULTS: A total of 532 documents were included. China contributed the highest number of publications (36.71%) and total citations [1,584]. Seoane J was the most prolific author [16 (h-index: 9)], while Warnakulasuriya S had the highest total link strength [282 (h-index: 7)] in co-citations. Oral Oncology was identified as the most prolific [231 (72.64%)], co-cited and impactful journal (h-index: 13). Explosions of citations were found for keywords such as "early diagnosis", "biomarker", "saliva", "precancer" and "prognosis", making it evident that in the field of oral cancer diagnosis there is room for new studies focusing in reducing the diagnostic interval, with the research hotspots being the terms "biomarkers", "imaging diagnosis" and "gene expression". CONCLUSIONS: This study provides valuable information that can help researchers and institutions align their research activities according to emerging themes, establish collaborations and allocate resources effectively.

The use of E-cigarettes as a risk factor for oral potentially malignant disorders and oral cancer: a rapid review of clinical evidence.

BACKGROUND: The popularity of e-cigarettes has increased rapidly in the last decade, particularly among teens and young adults, being advertised as a less harmful alternative to conventional tobacco products. However, in vitro and in vivo studies have evidenced a variable quantity of potentially harmful components and some recognized carcinogens which may cause DNA damage in oral cells. Additionally, evidence suggests that e-cigarettes may play active roles in the pathogenesis of other malignancies, such as lung and bladder cancers. Therefore, this rapid review aimed to assess the available clinical evidence about using e-cigarettes as a risk factor for oral potentially malignant disorders (OPMD) and oral cancer. MATERIAL AND METHODS: A systematic search for English language articles published was performed in PubMed (MEDLINE), Embase, Scopus, and Web of Science. After the study selection process, the authors included twelve clinical studies about OPMD and oral cancer risk in e-cigarette users. RESULTS: The main findings showed the presence of carcinogenic compounds in saliva and morphologic changes, DNA damage, and molecular pathways related to carcinogenesis in the oral cells of e-cigarette users. However, results were inconsistent compared to tobacco smokers and control groups. CONCLUSIONS: the current clinical evidence on this topic is limited and insufficient to support using e-cigarettes as a risk factor for OPMD and oral cancer. Nevertheless, dental care professionals should advise patients responsibly about the potentially harmful effects of e-cigarettes on the oral mucosa cells. Future long-term and well-designed clinical studies are needed.

Oral squamous cell carcinoma arising from areas of Graft-versus-host disease: A systematic review.

BACKGROUND: Graft-versus-host disease (GVHD) is an immune system reaction that occurs in patients with a history of hematopoietic stem cell transplantation (HSCT), in which the grafted donor's cells attack those of the host. The objective of this systematic review was to present a study on oral squamous cell carcinoma (OSSC) that developed from GVHD areas in patients undergoing HSCT. MATERIAL AND METHODS: An electronic search was conducted in the databases PUBMED, WEB OF SCIENCE, SCOPUS, MEDLINE and SCIENCE DIRECT, according to PRISMA guidelines. RESULTS: Of the 1582 results, 23 articles were included, resulting in 81 cases. The most common underlying disease for performing the transplant was Myeloid Leukemia (55.6%). The mean age was 39 years, with a predilection for males (64.2%). The tongue was the site of GVHD that most frequently underwent transformation to SCC (59.3%). The average time between transplantation and the development of GVHD was of approximately of 8 months, while the average period of development between transplantation and the development of OSCC was of approximately of 111 months. The most common treatment to GVHD was cyclosporine associated with corticosteroids. CONCLUSIONS: OSCCs arising from areas of GVHD present a different evolution from conventional oral carcinomas, since they affect younger patients, smoking and alcohol are not important etiological factors and finally because they present good prognosis, but further studies with larger number cases followed are needed to confirm our findings.

HPV-related oropharyngeal carcinoma remains infrequent over 25 years in a Brazilian Oral Pathology Center: A cross-sectional study with literature review.

BACKGROUND: The aim was to evaluate the frequency, clinicopathological features, and HPV status of oropharyngeal squamous cell carcinoma (OP-SCC) and benign HPV-related epithelial lesions of the oropharynx over the last 25 years. Moreover, a literature review was performed to investigate HPV frequency in OP-SCC samples diagnosed in Brazilian Centers. MATERIAL AND METHODS: A cross-sectional study analyzed OP-SCC, squamous papilloma, verruca vulgaris, and condyloma accuminatum, diagnosed from 1997 to 2021. HPV status of OP-SCC was determined by immunohistochemistry and "in situ" hybridization. Bivariate statistics were performed (p≤0.05). For the literature review, MEDLINE/PubMed, Web of Science, EMBASE, and Scopus were searched. Two independent reviewers assessed the studies for eligibility. RESULTS: Cross-sectional: 211 OP-SCC (63.0%) and 124 benign lesions (37.0%) were included. OP-SCC frequency increased gradually over time, whereas benign lesions had steady trends. OP-SCC affected more males (n= 171; 81.0%), though the relative frequency in females rose over time. Smoking (n= 127; 60.2%) was common in OP-SCC. Nineteen OP-SCC (13.0%) were positive for HPV. HPV-positive and HPV-negative tumors had similar clinicopathological features (p>0.05). Benign lesions predominated in middle-aged (n= 32; 26.7%) women (n= 71; 57.3%), in the soft palate (n=101; 81.5%). LITERATURE REVIEW: 32 studies were included, and in 60% of them, HPV frequency in OP-SCC was less than 25%. CONCLUSIONS: OP-SCC prevalence has been increasing, and it was mostly associated with smoking and alcohol rather than with HPV infection in Brazil. Benign lesions had a stationary frequency over the evaluated period.

Oral cancer screening outcomes in the Latin American region with special relevance to Brazil and Cuba: a systematic review.

BACKGROUND:  The Latin American region represents a hotspot for oral cancer incidence and mortality. To reduce oral cancer mortality rates, screening for early detection of subjects with suspicious or innocuous oral lesions has been promoted. A systematic review was performed to assess the outcomes of oral cancer screening in the Latin American region. MATERIAL AND METHODS:  An electronic search was conducted in eight databases and grey literature. The eligibility criteria included screening where adult participants underwent any screening test during an organized screening program. Screening programs were assessed to understand trends in oral cancer diagnosis. Rates of oral cancers diagnosed in screening programs were classified as increase, decrease, or stable based on each year assessed. RESULTS:  Following our searches, twelve studies conducted in Brazil and Cuba were included. The screening tests reported were visual oral examination (VOE) and in one study in addition light-based fluorescence testing. 13,277,608 individuals were screened and a total of 1,516 oral cancers were detected (0.01%). Only two studies aimed to screen high-risk individuals (smokers and drinkers). Oral cancer cases diagnosed during screening programs were proportionately stable over the years 1997 to 2009 but increased from 2010 to 2021. The fluorescence-associated VOE test demonstrated a sensitivity of 100% and a specificity of 90%. Similarly, the VOE test alone exhibited a sensitivity of 100%, with specificity ranging from 75% to 90%. CONCLUSIONS:  Screening studies conducted in Latin American countries had serious limitations both in methodology (lack of examiner training) and in reporting data (lack of description of clinical categories of screen positives). Capacitation of health workers to perform VOE in well-designed screening programs should be implemented.