Acute Suppurative Thyroiditis in Childhood: An Atypical Presentation.

Neck stiffness is a common clinical sign in children presenting to the emergency department that may indicate a wide variety of diagnoses. Acute suppurative thyroiditis (AST) is an infection of the thyroid gland caused by a bacterium, virus, or, less commonly, fungus. It presents as an acute or subacute development of an anterior cervical mass, with associated inflammatory signs. The pressure upon neck muscles may be reflected as a limitation of cervical mobility. AST is often preceded by an upper respiratory tract infection, and pyriform sinus fistula is the most common predisposing factor. It is particularly uncommon in the pediatric age, with limited cases reported in the literature. Therefore, a heightened suspicion is required for proper diagnosis and timely intervention, due to its high mortality. Prompt treatment with broad-spectrum parenteral antibiotic therapy and drainage is mandatory to prevent the numerous complications associated, namely, mediastinitis and sepsis. We report the case of a two-year-old female child admitted with a two-week history of intermittent high-grade fever and sore throat, followed by prostration and limitation in neck movement on admission. Examination revealed neck stiffness with positive Kernig and Brudzinski signs. The laboratory tests showed elevated inflammatory parameters. Cranial computed tomography (CT) scan and lumbar puncture were normal. On day 2 after admission, an anterior cervical mass with slight signs of fluctuation was detected. Ultrasound was compatible with a hemorrhagic/overinfected thyroid nodule, and the patient was started on broad-spectrum antibiotics. Due to clinical worsening, a cervical CT scan was performed, which documented a thyroid abscess with extension into the retropharyngeal space. She underwent surgical drainage, and Streptococcus anginosus and mixed anaerobes were isolated, sensitive to ongoing antibiotherapy. On multidisciplinary follow-up, an esophageal barium study, laryngoscopy, and cervical magnetic resonance imaging (MRI) were performed, revealing no anatomical defects. AST is a rare disease in children, but potentially fatal, so its early recognition and treatment are essential. We aim to draw attention to this disease and its differential diagnosis to reduce the associated morbimortality.

Kitul, a food plant with antidiabetic-like effects: Reduction of intracellular reactive species in glucose-stimulated RIN-5F pancreatic ß-cells and mitigation of pro-inflammatory mediators in activated RAW 264.7 macrophages.

Kitul (Caryota urens L.) inflorescences are broadly used for sweet sap production in Asian countries and Kitul food products are known as being suitable for diabetic patients. Considering the strong ability to inhibit α-glucosidase, we hypothesize that kitul antidiabetic properties might also involve the modulation of inflammatory pathways and hyperglycaemia-induced oxidative damage. Hence, the effects of an inflorescence's methanol extract were investigated in glucose-stimulated pancreatic cells (RIN-5F) and LPS-stimulated RAW 264.7 macrophages. The extract reduced the overproduction of intracellular reactive species in pancreatic cells and also NO, L-citrulline and IL-6 levels in LPS-stimulated RAW 264.7 macrophages. Inhibition of 5-lipoxygenase (IC50 = 166.1 µg/mL) through an uncompetitive manner was also recorded upon treatment with C. urens inflorescences extract. The phenolic profile of the inflorescences was characterized by HPLC-DAD, six hydroxycinnamic acids being identified and quantified. Overall, our data provide additional evidence on the pleiotropic mechanisms of Kitul inflorescences as an antidiabetic agent.

Genomic investigations of unexplained acute hepatitis in children.

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children.

We Are Concerned about the Future and We Are Here to Support the Change: Let's Talk and Work Together!

Scarcely explored, intergenerational dialogue may support the re-encounter between generations. BACKGROUND: Focused on intergenerational sharing and on the identification of differences between generations, the project #GenerationsWithAVoice aims to identify generational inequalities, with the aim of promoting awareness of intergenerational challenges, boosting public debate and interest in public policies. METHODS: Twenty focus groups were developed, and an evaluation instrument was applied. RESULTS: (i) Young people believe that they have more knowledge, but less propensity for action, leaving this task to the following generations; (ii) the family and housing emerge as the issues with the greatest number of problems identified, but also as important resources; (iii) government and politics, community and society, and the economy are of less interest and knowledge on the part of this generation; (iv) school seems to be the ideal scenario for the implementation of strategies that lead to change. CONCLUSIONS: We highlight the role of this work in the deconstruction of beliefs regarding previous generations, the development of knowledge, and the promotion of cohesion and social support.

Incremental Learning for Dermatological Imaging Modality Classification.

With the increasing adoption of teledermatology, there is a need to improve the automatic organization of medical records, being dermatological image modality a key filter in this process. Although there has been considerable effort in the classification of medical imaging modalities, this has not been in the field of dermatology. Moreover, as various devices are used in teledermatological consultations, image acquisition conditions may differ. In this work, two models (VGG-16 and MobileNetV2) were used to classify dermatological images from the Portuguese National Health System according to their modality. Afterwards, four incremental learning strategies were applied to these models, namely naive, elastic weight consolidation, averaged gradient episodic memory, and experience replay, enabling their adaptation to new conditions while preserving previously acquired knowledge. The evaluation considered catastrophic forgetting, accuracy, and computational cost. The MobileNetV2 trained with the experience replay strategy, with 500 images in memory, achieved a global accuracy of 86.04% with only 0.0344 of forgetting, which is 6.98% less than the second-best strategy. Regarding efficiency, this strategy took 56 s per epoch longer than the baseline and required, on average, 4554 megabytes of RAM during training. Promising results were achieved, proving the effectiveness of the proposed approach.

Integrating Domain Knowledge into Deep Learning for Skin Lesion Risk Prioritization to Assist Teledermatology Referral.

Teledermatology has developed rapidly in recent years and is nowadays an essential tool for early diagnosis. In this work, we aim to improve existing Teledermatology processes for skin lesion diagnosis by developing a deep learning approach for risk prioritization with a dataset of retrospective data from referral requests of the Portuguese National Health System. Given the high complexity of this task, we propose a new prioritization pipeline guided and inspired by domain knowledge. We explored automatic lesion segmentation and tested different learning schemes, namely hierarchical classification and curriculum learning approaches, optionally including additional patient metadata. The final priority level prediction can then be obtained by combining predicted diagnosis and a baseline priority level accounting for explicit expert knowledge. In both the differential diagnosis and prioritization branches, lesion segmentation with 30% tolerance for contextual information was shown to improve classification when compared with a flat baseline model trained on original images; furthermore, the addition of patient information was not beneficial for most experiments. Curriculum learning delivered better results than a flat or hierarchical approach. The combination of diagnosis information and a knowledge map, created in collaboration with dermatologists, together with the priority achieved interesting results (best macro F1 of 43.93% for a validated test set), paving the way for new data-centric and knowledge-driven approaches.

Valorisation of kitul, an overlooked food plant: Phenolic profiling of fruits and inflorescences and assessment of their effects on diabetes-related targets.

Caryota urens L. has long been valued as a traditional food, the edible fruits being eaten raw and the inflorescences commonly used on sweet sap and flour production. In the current work, the phenolic profile of methanol extracts obtained from the inflorescences and fruits was unveiled for the first time, nine caffeic acid derivatives being identified and quantified. Since kitul products have been reported for their antidiabetic properties, extracts radical scavenging activity and α-amylase, α-glucosidase and aldose reductase inhibitory activity were assessed. The inflorescences' extract was particularly active against yeast α-glucosidase (IC50 = 1.53 µg/mL), acting through a non-competitive inhibitory mechanism. This activity was also observed in enzyme-enriched homogenates obtained from human Caco-2 cells (IC50 = 64.75 µg/mL). Additionally, the extract obtained from the inflorescences showed no cytotoxicity on HepG2, AGS and Caco-2 cell lines. Our data suggest that C. urens inflorescences can support the development of new functional foods with α-glucosidase inhibitory activity.

Gustavia gracillima Miers. flowers effects on enzymatic targets underlying metabolic disorders and characterization of its polyphenolic content by HPLC-DAD-ESI/MSn.

Notwithstanding Gustavia gracillima Miers widespread distribution in neotropical regions, its chemical profile and biological properties remain uninvestigated. A methanol extract obtained from the flowers was characterized through HPLC-DAD-ESI/MSn, nine ellagic acid derivatives and twelve kaempferol 3-O-glycosides being identified and quantitated for the first time at the species and genus. Preliminary cytotoxicity screening did not reveal noticeable effects upon gastrointestinal representative cell lines (AGS, Caco-2 and Hep G2), which further prompted us to evaluate the impact in a series of targets involved in metabolic disorders and associated complications. Despite of the moderate inhibition towards 5-lipoxygense activity, G. gracillima methanol extract displayed significant effects on carbohydrates-hydrolysing enzymes. In contrast with the antidiabetic reference drug acarbose, the extract was able to selectively inhibit yeast α-glucosidase activity (IC50 = 4.72 µg/mL), with negligible inhibitory effects upon α-amylase. Kinetic studies pointed to a model of mixed inhibition with a great binding activity, characterized by an inhibitory constant of 2.91 µg/mL. The notable inhibitory activity was also confirmed in α-glucosidase homogenates isolated from human intestinal cells (IC50 = 34.03 µg/mL). Moreover, the extract obtained from the flowers of G. gracillima displayed significant aldose reductase inhibition (IC50 = 61.88 µg/mL), as well as O2- and NO scavenging properties. A moderate inhibitory effect was also recorded against pancreatic lipase (IC50 = 362.17 µg/mL) through a mixed inhibition mode. Recorded data supports the potential incorporation of G. gracillima flowers on antidiabetic herbal formulations and/or supplements, with not only straight action on carbohydrates digestion, but also direct interference with targets involved on subsequent diabetes events, such as triglycerides metabolism, inflammation and radical-mediated stress.

Medicinal plants utilized in Thai Traditional Medicine for diabetes treatment: Ethnobotanical surveys, scientific evidence and phytochemicals.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes mellitus remains the most lethal metabolic disease of contemporaneous times and despite the therapeutic arsenal currently available, research on new antidiabetic agents remains a priority. In recent years, the revitalization of Thai Traditional Medicine (TTM) became a clear priority for the Thai government, and many efforts have been undertaken to accelerate research on herbal medicines and their use in medical services in various hospitals. Additionally, and particularly in rural areas, treatment of diabetes and associated symptomatology frequently relies on herbal preparations recommended by practitioners of TTM. In the current work, medicinal plants used in Thailand for treating diabetes, as well as their hypoglycaemic pharmacological evidences and potential therapeutic use for diabetes-related complications were reviewed. MATERIALS AND METHODS: Ethnopharmacological information on the plant materials used in TTM for diabetes treatment was collected through literature search in a range of scientific databases using the search terms: diabetes, folk medicine, Thailand medicinal plants, traditional medicine. Information regarding scientific evidence on the antidiabetic effects of surveyed species was obtained considering not only the most common taxonomic designation, but also taxonomic synonyms, and including the keywords 'diabetes' and 'hypoglycaemic effect'. RESULTS: A total of 183 species known to be used for diabetes management in TTM were reviewed, with 30% of them still lacking experimental evidences to support claims regarding the mechanisms and phytochemicals underlying their antidiabetic properties. Moreover, a total of 46 bioactives displaying effective antidiabetic effects have been isolated from 24 species, their underlying mechanism(s) of action being fully or partially disclosed. CONCLUSIONS: We deliver the most extensive survey dealing with the ethnomedicinal knowledge of Thai medicinal plants utilized on diabetes management. We are certain that the current review will spark further research on Thai plants for the development of new standardized phytomedicines through drug discovery programmes.

Data Augmentation Using Adversarial Image-to-Image Translation for the Segmentation of Mobile-Acquired Dermatological Images.

Dermoscopic images allow the detailed examination of subsurface characteristics of the skin, which led to creating several substantial databases of diverse skin lesions. However, the dermoscope is not an easily accessible tool in some regions. A less expensive alternative could be acquiring medium resolution clinical macroscopic images of skin lesions. However, the limited volume of macroscopic images available, especially mobile-acquired, hinders developing a clinical mobile-based deep learning approach. In this work, we present a technique to efficiently utilize the sizable number of dermoscopic images to improve the segmentation capacity of macroscopic skin lesion images. A Cycle-Consistent Adversarial Network is used to translate the image between the two distinct domains created by the different image acquisition devices. A visual inspection was performed on several databases for qualitative evaluation of the results, based on the disappearance and appearance of intrinsic dermoscopic and macroscopic features. Moreover, the Fréchet Inception Distance was used as a quantitative metric. The quantitative segmentation results are demonstrated on the available macroscopic segmentation databases, SMARTSKINS and Dermofit Image Library, yielding test set thresholded Jaccard Index of 85.13% and 74.30%. These results establish a new state-of-the-art performance in the SMARTSKINS database.

Phenolic Profiling and Biological Potential of Ficus curtipes Corner Leaves and Stem Bark: 5-Lipoxygenase Inhibition and Interference with NO Levels in LPS-Stimulated RAW 264.7 Macrophages.

The economic value of fig trees has been globally acknowledged due to their utilization in the food industry, being also frequently used in traditional medicine. While ubiquitously distributed in Southeast Asia, Ficus curtipes Corner remains uninvestigated concerning its biological properties and chemical profile. HPLC-DAD-ESI/MSn characterization of methanol extracts obtained from the stem bark and leaves allowed the identification and quantitation of 21 phenolic compounds for the first time; the stem bark was predominantly rich in flavan-3-ols and apigenin derivatives, while solely apigenin-di-glycosides have been identified and quantitated on the leaf extract. Both extracts inhibited 5-lipoxygenase (5-LOX) activity in a concentration-dependent manner, the one obtained from the stem bark being significantly more active (IC50 = 10.75 µg/mL). The effect of both extracts on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages was evaluated, and while the stem bark extract did not lead to a noticeable interference on nitric oxide (NO) levels, the extract obtained from the leaves notably decreased NO and L-citrulline levels at concentrations ranging from 250 to 500 µg/mL. Herein, F. curtipes is valorized due to its modulatory effects on inflammatory mediators and also as a source of bioactive phenols, which may fuel further studies on the development of nutraceuticals.

HIV treatment and care services for adolescents: a situational analysis of 218 facilities in 23 sub-Saharan African countries.

INTRODUCTION: In 2013, an estimated 2.1 million adolescents (age 10-19 years) were living with HIV globally. The extent to which health facilities provide appropriate treatment and care was unknown. To support understanding of service availability in 2014, Paediatric-Adolescent Treatment Africa (PATA), a non-governmental organisation (NGO) supporting a network of health facilities across sub-Saharan Africa, undertook a facility-level situational analysis of adolescent HIV treatment and care services in 23 countries. METHODS: Two hundred and eighteen facilities, responsible for an estimated 80,072 HIV-infected adolescents in care, were surveyed. Sixty per cent of the sample were from PATA's network, with the remaining gathered via local NGO partners and snowball sampling. Data were analysed using descriptive statistics and coding to describe central tendencies and identify themes. RESULTS: Respondents represented three subregions: West and Central Africa (n = 59; 27%), East Africa (n = 77, 35%) and southern Africa (n = 82, 38%). Half (50%) of the facilities were in urban areas, 17% peri-urban and 33% rural settings. Insufficient data disaggregation and outcomes monitoring were critical issues. A quarter of facilities did not have a working definition of adolescence. Facilities reported non-adherence as their key challenge in adolescent service provision, but had insufficient protocols for determining and managing poor adherence and loss to follow-up. Adherence counselling focused on implications of non-adherence rather than its drivers. Facilities recommended peer support as an effective adherence and retention intervention, yet not all offered these services. Almost two-thirds reported attending to adolescents with adults and/or children, and half had no transitioning protocols. Of those with transitioning protocols, 21% moved pregnant adolescents into adult services earlier than their peers. There was limited sexual and reproductive health integration, with 63% of facilities offering these services within their HIV programmes and 46% catering to the special needs of HIV-infected pregnant adolescents. CONCLUSIONS: Results indicate that providers are challenged by adolescent adherence and reflect an insufficiently targeted approach for adolescents. Guidance on standard definitions for adherence, retention and counselling approaches is needed. Peer support may create an enabling environment and sensitize personnel. Service delivery gaps should be addressed, with standardized transition and quality counselling. Integrated, comprehensive sexual reproductive health services are needed, with support for pregnant adolescents.

What is it going to take to move youth-related HIV programme policies into practice in Africa?

INTRODUCTION: HIV has been reported to be the leading cause of mortality amongst adolescents in Africa. This has brought attention to the changes in service provision and health management that many adolescents living with HIV experience when transferring from specialized paediatric- or adolescent-focused services to adult care. When transition is enacted poorly, adherence may be affected and the continuum of care disrupted. As the population of HIV-infected adolescents grows, effective and supported transition increases in significance as an operational imperative. DISCUSSION: Considerable gaps remain in moving policy to practice at global, national, and local levels. Policies that give clear definition to transition and provide standard operating procedures or tools to support this process are lacking. National guidelines tend to neglect transition. Beyond transition itself, there has been slow progress on the inclusion of adolescents in national policies and strategies. Guidance often overlooks the specific needs and rights of adolescents, in particular for those living with HIV. In some cases, prohibitive laws can impede adolescent access by applying age of consent restriction to HIV testing, counselling and treatment, as well as SRH services. Where adolescent-focused policies do exist, they have been slow to emerge as tangible operating procedures at health facility level. A key barrier is the nature of existing transition guidance, which tends to recommend an individualized, client-centred approach, driven by clinicians. In low- and middle-income settings, flexible responses are resource intensive and time consuming, and therefore challenging to implement amidst staff shortages and administrative challenges. First, national governments must adopt transition-specific policies to ensure that adolescents seamlessly receive appropriate and supportive care. Second, transition policies must form part of a broader adolescent-centred policy landscape and adolescent-friendly orientation and approach at health system level. Third, national actors must ensure that transition policies are supported at implementation level. Fourth, youth involvement and community mobilization are essential. Finally, further implementation research is urgently needed to better understand how to support young people and providers in achieving smooth transitions. CONCLUSIONS: Only by moving from policy to practice through supportive policies and their implementation will we be closer to including adolescents in the 2030 goal of ending AIDS.