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INTRODUCTION: The scientific community highlighted the relevance of 3D physical models since the beginning of the XXI century, complementary to three-dimensional(3D) digital volume by computer tomography, to support court discussions on medico-legal issues. The recreation of 3D evidence can be an important tool for investigators and experts, providing a better understanding of the causes and circumstances of the events involved in a crime. OBJECTIVE: The present study aims to assess the reproducibility of 3D printed and 3D tomographic volumes generated from mandibles following simulated forensic injuries, highlighting the recreation of crime tools. MATERIAL AND METHODS: Concerning the study design presented, data collection was performed in three phases. Nine simulated injuries of forensic interest were selected (phase1) and all the mandibles were scanned tomographically, individually, by Cone Beam Computed Tomography CBCT (phase 2). Then, in phase 3, the DICOM images were used for 3D printing with the Ender 3® printer by the Fused Deposition Modeling (FDM) technique. The data analysis followed two procedures: the comparison between the artificial mandible and 3D tomographic volume (AT) and the comparison between the artificial mandible and 3D printed volume, or the copy (AC). Data were analyzed using T-Student and ICC tests and presented in Bland-Altman plots. CONCLUSION: The analogic technique applied in 3D printed volume, when compared with computerized technique, using 3D digital images and measurement, showed to be accurate and reproducible. Further studies are needed in search of standardization for three-dimensional measurements in digitized and printed volumes.
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Background/Objectives: Burning Mouth Syndrome (BMS) patients experience a reduction in health-related quality of life and an increased intake of medication. Photobiomodulation with low-level laser therapy has been demonstrated to be an efficacious treatment for BMS. However, its long-term benefits remain relatively unknown. This study aimed to evaluate the impact of prolonged Photobiomodulation with low-level laser therapy on BMS patients by examining the efficacy of an outpatient protocol in a real-world setting. Methods: A prospective study was designed to address the research question. Photobiomodulation was performed, irradiating the affected areas once every two weeks for 12 months. Health-related quality of life was assessed using the EQ-5D-5L questionnaire at the initial consultation and after 6 months and 12 months of treatment. Additionally, the patients' pharmacological profile was also monitored. Nonparametric statistical analysis was performed (p < 0.05 was considered statistically significant). Results: The study was completed by 15 individuals, comprising 14 females and 1 male. The results indicated a statistically significant improvement (p < 0.001) in four of the five dimensions of the health-related quality of life questionnaire, namely self-care, usual activities, pain/discomfort, and anxiety/depression, along with the patients' perceived health level. A total of 13 participants reported suspending or reducing their intake of medications for Burning Mouth Syndrome. Conclusions: Therefore, Photobiomodulation with low-level laser therapy has a positive effect on improving patients' quality of life and reducing BMS symptoms, contributing to a subsequent reduction or suspension of previous medications. These findings support the efficacy of the applied protocol. Given the innovative methodology and promising results, further research is warranted.
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In forensic scenarios, such as armed conflicts or mass disasters, the oral cavity can be a valuable source of identification information relevant to legal issues. In many European Union countries, it is mandatory to register dental records for identification purposes. A pilot and quasi-experimental study was performed. The study aims to analyze two methodologies, photography and wireless intraoral (IO) laser scanner, in the scope of the orofacial record in forensic pathology, highlighting their impact on human identification. The IO scanner i700 (Medit, Lusobionic, Portugal) and Canon 5D-Full Frame equipment were used to record the individual status, living patients (n = 5), and forensic cases (n = 5). IO and extraoral anatomical structures were recorded following six parameters: time, mineralized and soft detail, communication, extra devices, and distortion. The statistical analysis was performed in accordance with a scoring system and Mann-Whitney (P < 0.05) analysis. The photography method recorded extraoral data for all samples (score range between 15 and 23). The time elapsed to complete an IO scan in forensic cases was shorter than with photography, without requiring additional sources of light or mirror devices. Living patients and corpses identified statistically significant differences. It can be concluded that laser scanners are a valuable tool in the field of forensic pathology and can be used to record and analyze anatomic-morphological data for identification purposes accurately. Key points: Human identification engages in orofacial details records.Photographic and laser scans record intraoral and extraoral anatomic structures.Forensic cases assessed by intraoral scanner technology are accurate and less time-consuming, optimizing the orofacial data for identification.
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While clinical dentistry has seamlessly integrated the digital revolution, there is a gap in the technological capabilities of forensic dentistry.The study aimed to compare the superimposition accuracy of two different three-dimensional record formats, namely the intraoral scanner and cone beam computer tomography, in the context of forensic identification.The sample consisted of randomly selected adults (n=10) of both sexes aged between 20 and 50 years. Following the acquisition of data using the Medit i700 wireless scanner and the iCAT Tomograph with InVivo software, the records were analysed and compared through superimposition using Medit Scan Clinic software to assess the technical precision of anatomical identification details.The results obtained through the superimposition of dental and bone records following intra- and inter-observer analysis enabled an accurate comparison and identification of an individual. This method can differentiate between positive and negative matches, achieving exclusion results and offering a potential solution to overcoming the absence of a standardisation procedure in human identification.
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Tomografía Computarizada de Haz Cónico , Odontología Forense , Imagenología Tridimensional , Programas Informáticos , Humanos , Masculino , Adulto , Femenino , Odontología Forense/métodos , Adulto Joven , Persona de Mediana Edad , Procesamiento de Imagen Asistido por ComputadorRESUMEN
BACKGROUND: Progressive familial intrahepatic cholestasis (PFIC) is a group of autosomal recessive disorders, the most prevalent being BSEP deficiency, resulting in disrupted bile formation, cholestasis, and pruritus. Building on a previous phase 2 study, we aimed to evaluate the efficacy and safety of maralixibat-an ileal bile acid transporter inhibitor-in participants with all types of PFIC. METHODS: MARCH-PFIC was a multicentre, randomised, double-blind, placebo-controlled, phase 3 study conducted in 29 community and hospital centres across 16 countries in Europe, the Americas, and Asia. We recruited participants aged 1-17 years with PFIC with persistent pruritus (>6 months; average of ≥1·5 on morning Itch-Reported Outcome [Observer; ItchRO(Obs)] during the last 4 weeks of screening) and biochemical abnormalities or pathological evidence of progressive liver disease, or both. We defined three analysis cohorts. The BSEP (or primary) cohort included only those with biallelic, non-truncated BSEP deficiency without low or fluctuating serum bile acids or previous biliary surgery. The all-PFIC cohort combined the BSEP cohort with participants with biallelic FIC1, MDR3, TJP2, or MYO5B deficiencies without previous surgery but regardless of bile acids. The full cohort had no exclusions. Participants were randomly assigned (1:1) to receive oral maralixibat (starting dose 142·5 µg/kg, then escalated to 570 µg/kg) or placebo twice daily for 26 weeks. The primary endpoint was the mean change in average morning ItchRO(Obs) severity score between baseline and weeks 15-26 in the BSEP cohort. The key secondary efficacy endpoint was the mean change in total serum bile acids between baseline and the average of weeks 18, 22, and 26 in the BSEP cohort. Efficacy analyses were done in the intention-to-treat population (all those randomly assigned) and safety analyses were done in all participants who received at least one dose of study drug. This completed trial is registered with ClinicalTrials.gov, NCT03905330, and EudraCT, 2019-001211-22. FINDINGS: Between July 9, 2019, and March 4, 2022, 125 patients were screened, of whom 93 were randomly assigned to maralixibat (n=47; 14 in the BSEP cohort and 33 in the all-PFIC cohort) or placebo (n=46; 17 in the BSEP cohort and 31 in the all-PFIC cohort), received at least one dose of study drug, and were included in the intention-to-treat and safety populations. The median age was 3·0 years (IQR 2·0-7·0) and 51 (55%) of 93 participants were female and 42 (45%) were male. In the BSEP cohort, least-squares mean change from baseline in morning ItchRO(Obs) was -1·7 (95% CI -2·3 to -1·2) with maralixibat versus -0·6 (-1·1 to -0·1) with placebo, with a significant between-group difference of -1·1 (95% CI -1·8 to -0·3; p=0·0063). Least-squares mean change from baseline in total serum bile acids was -176 µmol/L (95% CI -257 to -94) for maralixibat versus 11 µmol/L (-58 to 80) for placebo, also representing a significant difference of -187 µmol/L (95% CI -293 to -80; p=0·0013). The most common adverse event was diarrhoea (27 [57%] of 47 patients on maralixibat vs nine [20%] of 46 patients on placebo; all mild or moderate and mostly transient). There were five (11%) participants with serious treatment-emergent adverse events in the maralixibat group versus three (7%) in the placebo group. No treatment-related deaths occurred. INTERPRETATION: Maralixibat improved pruritus and predictors of native liver survival in PFIC (eg, serum bile acids). Maralixibat represents a non-surgical, pharmacological option to interrupt the enterohepatic circulation and improve the standard of care in patients with PFIC. FUNDING: Mirum Pharmaceuticals.
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Colestasis Intrahepática , Prurito , Humanos , Método Doble Ciego , Masculino , Femenino , Colestasis Intrahepática/tratamiento farmacológico , Colestasis Intrahepática/sangre , Niño , Adolescente , Preescolar , Lactante , Prurito/etiología , Prurito/tratamiento farmacológico , Resultado del Tratamiento , Miembro 11 de la Subfamilia B de Transportador de Casetes de Unión al ATP/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/deficienciaRESUMEN
A comprehensive analysis was performed, considering blockchain technology (BT) properties in digital health, addressing medicolegal, privacy, and regulatory considerations. Adherence to personal data protection and healthcare regulatory guidelines were analyzed and compared for GDPR (Europe), HIPAA (United States), CCPA (California), PIPEDA (Canada), the Privacy Act of 1988 (Australia), APPI (Japan), and LGPD (Brazil). Issues such as health systems, strengthening and aligning policy orientations and initiatives, and emphasizing the role of data analysis in shaping health policies were explored. The study addressed conflicts between the legal frameworks and blockchain, comparing and suggesting solutions like the revision of laws and the integration of compliance mechanisms. Additionally, it sought to enhance IT-health literacy by integrating the healthcare and legal domains. Ongoing collaboration between legal, health, and IT experts is essential for designing systems that effectively balance privacy rights and data protection while maximizing the benefits of disruptive technologies like blockchain.
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Cadena de Bloques , Tecnología Disruptiva , Seguridad Computacional , Privacidad , Difusión de la InformaciónRESUMEN
The International Consortium Network/Orofacial Pain Special Interest Group focuses on temporomandibular disease diagnosis procedure guidelines as a reference iQAn this scope. Concerning this reference, the aim of this study was to comprehensively analyze injury and sequela frames within European and American approaches to personal damage. A quasiexperimental pilot study of Portuguese orofacial trauma cases in a medico-legal evaluation database was performed with an interrupted time series design. The clinical data were recorded following five criteria of TMJ diagnosis (jaw opening, pain, anatomical deficit, functional deficit, clinical sounds, and occlusal deficit) under three degrees of severity. The injury frame evaluation was recorded in the first-degree stage in all criteria. Pain, as a sequela, was the criterion present in 45% of the sample as spontaneous (20%) or stimulated (25%). Temporomandibular trauma damage evaluation emphasizes the accurate injury diagnosis and sequela framework. Orofacial trauma analysis should focus on the inclusion or exclusion of a TMD diagnosis. This study suggests revising the reference tables on personal damage, considering the inclusion of TMD and its categorization and impact.
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BACKGROUND: Neonatal coccidiosis is a common and important disease of suckling piglets in modern farming caused by Cystoisospora suis. Prevalence rates are high, namely, in Portugal, although no recent data are available. The metaphylactic administration of a single dose of toltrazuril and hygienic measures are the backbone of control strategies on positive farms. However, several studies have shown that these programs are not always effective, underlining the need to revise the risk factors and control strategies currently applied. The present study evaluated C. suis prevalence on Portuguese farms and assessed the risk factors associated with facilities and farm rearing practices. RESULTS: From the 27 tested farms, 23 were positive to Cystoisopora suis (85.2%). In total, 258 litters were sampled (accounting for 516 samples-2 samples per litter), with an average of 59.7% of positive litters per positive farm. Faecal pools from litters, in which liquid faeces predominated had a higher probability of containing oocysts than litter pools with mainly solid (Odds Ratio: 9.87; p < 0.0001) or pasty faeces (OR: 7.05; p = 0.001), and samples obtained from younger animals had higher oocyst counts (coefficient: - 0.0720; 95% CI - 0.125; - 0.019). No significant effect of toltrazuril administration was observed on the positivity rate, and none of the tested farms used disinfectants with official claims against parasites and known anticoccidial effects (e.g., cresol-based products). CONCLUSIONS: The C. suis prevalence on Portuguese swine farms appears to be similar to the prevalence found in other European countries. Repeated sampling of the same litter and the use of autofluorescence microscopy after a modified Ritchie technique seems to have increased sensitivity and consequently the detection rate of positive litters. Finally, despite the common use of oral toltrazuril, C. suis control programs appear to not always be effective (based on the detection of oocysts in faecal samples), suggesting the need to revise the control strategies applied in the field, including management factors and choices of disinfectant products.
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The leaf epidermis is the outermost cell layer forming the interface between plants and the atmosphere that must both provide a robust barrier against (a)biotic stressors and facilitate carbon dioxide uptake and leaf transpiration.1 To achieve these opposing requirements, the plant epidermis developed a wide range of specialized cell types such as stomata and hair cells. Although factors forming these individual cell types are known,2,3,4,5 it is poorly understood how their number and size are coordinated. Here, we identified a role for BdPRX76/BdPOX, a class III peroxidase, in regulating hair cell and stomatal size in the model grass Brachypodium distachyon. In bdpox mutants, prickle hair cells were smaller and stomata were longer. Because stomatal density remained unchanged, the negative correlation between stomatal size and density was disrupted in bdpox and resulted in higher stomatal conductance and lower intrinsic water-use efficiency. BdPOX was exclusively expressed in hair cells, suggesting that BdPOX cell-autonomously promotes hair cell size and indirectly restricts stomatal length. Cell-wall autofluorescence and lignin stainings indicated a role for BdPOX in the lignification or crosslinking of related phenolic compounds at the hair cell base. Ectopic expression of BdPOX in the stomatal lineage increased phenolic autofluorescence in guard cell (GC) walls and restricted stomatal elongation in bdpox. Together, we highlight a developmental interplay between hair cells and stomata that optimizes epidermal functionality. We propose that cell-type-specific changes disrupt this interplay and lead to compensatory developmental defects in other epidermal cell types.
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Brachypodium , Estomas de Plantas , Estomas de Plantas/fisiología , Brachypodium/genética , Peroxidasa/metabolismo , Hojas de la Planta/fisiología , Peroxidasas/metabolismoRESUMEN
Today, it is recognized that medicines will eventually be needed during pregnancy to help prevent to, ameliorate or treat an illness, either due to gestation-related medical conditions or pre-existing diseases. Adding to that, the rate of drug prescription to pregnant women has increased over the past few years, in accordance with the increasing trend to postpone childbirth to a later age. However, in spite of these trends, information regarding teratogenic risk in humans is often missing for most of the purchased drugs. So far, animal models have been the gold standard to obtain teratogenic data, but inter-species differences have limited the suitability of those models to predict human-specific outcomes, contributing to misidentified human teratogenicity. Therefore, the development of physiologically relevant in vitro humanized models can be the key to surpassing this limitation. In this context, this review describes the pathway towards the introduction of human pluripotent stem cell-derived models in developmental toxicity studies. Moreover, as an illustration of their relevance, a particular emphasis will be placed on those models that recapitulate two very important early developmental stages, namely gastrulation and cardiac specification.
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Células Madre Pluripotentes , Teratogénesis , Embarazo , Animales , Femenino , Humanos , Teratógenos/farmacologíaRESUMEN
When long-term biosignal monitoring is required via surface electrodes, the use of conventional silver/silver chloride (Ag/AgCl) gelled electrodes may not be the best solution, as the gel in the electrodes tends to dry out over time. In this work, the electrical behaviour and performance of dry electrodes for biopotential monitoring was assessed. Three materials were investigated and compared against the gold-standard Ag/AgCl gelled electrodes. To characterize their electrical behaviour, the impedance response over the frequency was evaluated, as well as its signal to noise ratio. The electrodes' performance was evaluated by integrating them in a proven electrocardiogram (ECG) acquisition setup where an ECG signal was acquired simultaneously with a set of dry electrodes and a set of standard Ag/AgCl gelled electrodes as reference. The obtained results were morphologically compared using the Normalised Root Mean Squared Error (nRMSE) and the Cosine Similarity (CS). The findings of this work suggest that the use of dry electrodes for biopotential monitoring is a suitable replacement for the conventional Ag/AgCl gelled electrodes. The signal obtained with dry electrodes is comparable to the one obtained with the gold standard, with the advantage that these do not require the use of gel and can be easily integrated into fabric to facilitate their use in long-term monitoring scenarios.
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Textiles , Dispositivos Electrónicos Vestibles , Electrocardiografía/métodos , Impedancia Eléctrica , ElectrodosRESUMEN
INTRODUCTION: The SARS-CoV-2 pandemic has reshaped the global landscape as we know it and had a tremendous effect on healthcare systems around the world. However, its impact on oral healthcare is still to be fully assessed. The aim of this study was to understand if and how COVID-19 affected the demand and performance of oral healthcare, taking the Clinical and Academic Centre of Coimbra as an example, more specifically, the Department of Stomatology of the Coimbra Hospital and University Centre and the Dentistry Department of the Faculty of Medicine of the University of Coimbra. MATERIAL AND METHODS: An observational study was designed for collecting the data of a series of key oral healthcare indicators: number of appointments; referrals from primary healthcare; missed appointments; number of surgeries performed in the operating room; number of biopsies; number of patients admitted through the emergency department and epidemiologic parameters over two 18-month periods between September 2018 and August 2021: pre-COVID-19 and during the COVID-19 pandemic, with the latter divided in four stages. A statistical analysis which included descriptive and inferential procedures was then performed, with an established significance level of 5% and the application of parametric tests, t-Student test for a sample and for independent samples and One-Way ANOVA for the variance analysis. RESULTS: There was a general decline in all indicators comparing the pre-COVID-19 with the COVID-19 period, with a reduction of 50.61% in the number of appointments, 44.06% in referrals, 24.41% in surgeries, 26.30% in biopsies and 32.33% in patients seen in the Emergency Room. The number of missed appointments also increased by 181.82%. All variations revealed statistically significant differences (p < 0.05). The individual COVID-19 stage analysis, when compared with the pre-COVID-19 reference, and variance analysis of these different stages also showed statistically significant differences (p < 0.05 and p < 0.001), except for the number of biopsies during the third and fourth stages. CONCLUSION: The results of this study suggest that the SARS-CoV-2 pandemic has had a considerable impact on oral healthcare demand and performance. However, results also show a remarkable adjustment and improvement in the provided care, with a positive evolution throughout the COVID-19 period.
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COVID-19 , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Pandemias , Portugal/epidemiología , Atención a la SaludRESUMEN
Physical violence against children and adolescents is an issue of Global Public Health. This study aims to identify traumatic injuries and the medicolegal temporary framework of the victim's profile in the European legal approach. Participants and setting include the following: the clinical reports of a Portuguese European Clinical Academic Center database were analysed. An observational and prospective cohort study was performed. A descriptive analysis of the variables was conducted, considering gender, bimodal age groups, place of residence, offender data, place of occurrence, aetiology, localization, type of injuries, personal injury assessment by Quantum doloris, and injury time. The statistical analysis was performed by Spearman's rho and Kendall's tau-b correlation tests, Pearson's chi-square test of independence (χ2), and Mann-Whitney and Kruskal-Wallis nonparametric tests (P < 0.05). The relationship between age groups and the place of occurrence was statistically significant (P = 0.001). Orofacial and nonorofacial injuries were related (P = 0.035). The General Data Protection Regulation is not a barrier to the treatment and sharing of justified data but a framework for safeguarding individuals' fundamental rights, including the Right to Health. Meticulous reporting of the clinical situation involves the victim, the occurrence, and the potential offender. Key points: An oral health professional's notification of the event is a fundamental step of the judicial process.The timeline is the core of traumatic injury assessment in a child physical abuse scenario.Medicolegal evaluation impacts disability prevention, imputability, and notification of the crime.
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The establishment of anthropometric measurements is of fundamental importance for the correct identification of human bodies. The objective of this study was to evaluate the accuracy and reliability of two-dimensional craniometric landmarks obtained from three-dimensional cone beam computed tomography reconstructions for forensic identification of humans. Computed tomography images with voxel sizes of 0.25, 0.3, and 0.4 mm were obtained using i-CAT® three-dimensional equipment. Ten landmarks were randomly selected, and 10 measurements were demarcated in the three-dimensional reconstruction to evaluate the mandibular condyle, ramus, and body. This study demonstrated that protocols with voxels of 0.3 mm should be preferentially indicated for the evaluation of linear and angular measurements. Implementing our methodology using prototypes for clinical and forensic simulations allows comparisons with human databases in identification issues.
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Grass stomata recruit lateral subsidiary cells (SCs), which are key to the unique stomatal morphology and the efficient plant-atmosphere gas exchange in grasses. Subsidiary mother cells (SMCs) strongly polarise before an asymmetric division forms a SC. Yet apart from a proximal polarity module that includes PANGLOSS1 (PAN1) and guides nuclear migration, little is known regarding the developmental processes that form SCs. Here, we used comparative transcriptomics of developing wild-type and SC-less bdmute leaves in the genetic model grass Brachypodium distachyon to identify novel factors involved in SC formation. This approach revealed BdPOLAR, which forms a novel, distal polarity domain in SMCs that is opposite to the proximal PAN1 domain. Both polarity domains are required for the formative SC division yet exhibit various roles in guiding pre-mitotic nuclear migration and SMC division plane orientation, respectively. Nonetheless, the domains are linked as the proximal domain controls polarisation of the distal domain. In summary, we identified two opposing polarity domains that coordinate the SC division, a process crucial for grass stomatal physiology.
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Hojas de la Planta , Estomas de Plantas , Estomas de Plantas/fisiología , División Celular , División Celular Asimétrica , Poaceae , Polaridad CelularRESUMEN
The increase of forcibly displaced people worldwide is a challenge for health systems and their ability to provide access and equity in Health as a universal right. Health information systems should be strengthened to collect and disseminate migrant health data enabling analytics for strategic decisions.This Viewpoint focuses on blockchain technology as an emergent digital tool to improve communication and overcome gaps in medical data sharing, conceptualizing a global health space. Anchored in the security, privacy, and medico-legal regulation of medical data, Blockchain technology would empower inter-organizational services or workflows, in real-time, by the users, inside and outside the national health systems, anywhere in the world. As an innovative approach, this Viewpoint highlights the future directions in IT-supported health.
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Cadena de Bloques , Humanos , Difusión de la Información , Privacidad , Tecnología , Cobertura Universal del Seguro de SaludRESUMEN
Background: The increase of forcibly displaced people worldwide is a challenge for health systems and their ability to provide access and equity in Health as a universal right. In the case of migrants and refugees, their journey exacerbates this challenge, as they go through diverse countries, camps, and humanitarian teams. Hence, the collection and analysis of health data are essential in providing quality care. The scientific community has been studying health digital technologies to answer health data consolidation, transparency, and global surveillance efficiency issues. Observing some empirical experiments with Blockchain in migrants and refugee health, we assessed the state-of-the-art by conducting a literature review. Methods: Blockchain applications are still emerging, which means that peer-reviewed literature may still be scarce in life science databases. Therefore, to gather the most appropriate available evidence, we used a diverse and balanced set of databases that compile articles and journals from different fields. We used a multi-step scoping review to refine search keywords and analyse the literature. We included studies between 2008 and 2021 that reported value, utility, or use cases of Blockchain in support of migrant and refugee health. Results: We identified a total of 69 articles, with 22 retained for full-text analysis and 8 of those being relevant. We employed Rayyan application to manage and evaluate the references by two researchers working independently. We identified two main uses of Blockchain technology to support migrant and refugee health: mitigate the lack of personal identification and make health records available. Blockchain also promotes data reliability in humanitarian aid, academic certificates, legal contracts, and financial transactions. Conclusions: The availability of reliable information about individuals facilitates universal health coverage, improves cooperation between diaspora-related countries, and supports global health efficiency in line with the third goal of the Sustainable Development Goals 2030 agenda. Given its characteristics of decentralization, resilience, transparency, and auditability, Blockchain remains a promising avenue for future research in migrant and refugee health.
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Cadena de Bloques , Refugiados , Migrantes , Humanos , Reproducibilidad de los Resultados , TecnologíaRESUMEN
Actinobacillus pleuropneumoniae (APP) is the causative agent of porcine pleuropneumonia, resulting in high economic impact worldwide. There are currently 19 known serovars of APP, with different ones being predominant in specific geographic regions. Outbreaks of pleuropneumonia, characterized by sudden respiratory difficulties and high mortality, can occur when infected pigs are brought into naïve herds, or by those carrying different serovars. Good biosecurity measures include regular diagnostic testing for surveillance purposes. Current gold standard diagnostic techniques lack sensitivity (bacterial culture), require expensive thermocycling machinery (PCR) and are time consuming (culture and PCR). Here we describe the development of an isothermal point-of-care diagnostic test - utilizing recombinase polymerase amplification (RPA) for the detection of APP, targeting the species-specific apxIVA gene. Our APP-RPA diagnostic test achieved a sensitivity of 10 copies/µL using a strain of APP serovar 8, which is the most prevalent serovar in the UK. Additionally, our APP-RPA assay achieved a clinical sensitivity and specificity of 84.3 and 100%, respectively, across 61 extracted clinical samples obtained from farms located in England and Portugal. Using a small subset (n = 14) of the lung tissue samples, we achieved a clinical sensitivity and specificity of 76.9 and 100%, respectively) using lung imprints made on FTA cards tested directly in the APP-RPA reaction. Our results demonstrate that our APP-RPA assay enables a suitable rapid and sensitive screening tool for this important veterinary pathogen.
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Stomata are cellular pores on the leaf epidermis that allow plants to regulate carbon assimilation and water loss. Stomata integrate environmental signals to regulate pore apertures and adapt gas exchange to fluctuating conditions. Here, we quantified intraspecific plasticity of stomatal gas exchange and anatomy in response to seasonal variation in Brachypodium distachyon. Over the course of 2 years, we (a) used infrared gas analysis to assess light response kinetics of 120 Bd21-3 wild-type individuals in an environmentally fluctuating greenhouse and (b) microscopically determined the seasonal variability of stomatal anatomy in a subset of these plants. We observed systemic environmental effects on gas exchange measurements and remarkable intraspecific plasticity of stomatal anatomical traits. To reliably link anatomical variation to gas exchange, we adjusted anatomical g smax calculations for grass stomatal morphology. We propose that systemic effects and variability in stomatal anatomy should be accounted for in long-term gas exchange studies.
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The quinolinic ring, present in several molecules, possesses a great diversity of biological activities. Therefore, this ring is in the structural composition of several candidates of drugs in preclinical and clinical studies; thus, it is necessary to compile these results to facilitate the design of new drugs. For this reason, some of the activities of compounds are selected to examine in this review, such as antimalarial, antimicrobial, anticancer, anti-inflammatory, antidiabetic, anti-rheumatic, and antiviral activities. All publications of scientific articles chosen are dated between 2000 and 2020. In addition to presenting the structures of some natural and synthetic compounds with their activities, we have listed the clinical studies of phases III and IV on antimalarial drugs containing the quinoline nucleus and phase III clinical studies on hydroxychloroquine and chloroquine to assess their possible role in COVID-19. Finally, we have reviewed some of the mechanisms of action, as well as the side effects of some of the quinolinic derivatives.