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Background: In phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Our aim was to assess different weaning approaches used by health professionals across Europe. Methods: A cross sectional questionnaire (survey monkey®) composed of 31 multiple and single choice questions was sent to European colleagues caring for inherited metabolic disorders (IMD). Centres were grouped into geographical regions for analysis. Results: Weaning started at 17–26 weeks in 85% (n = 81/95) of centres, >26 weeks in 12% (n = 11/95) and 26 weeks. First solids were mainly low Phe vegetables (59%, n = 56/95) and fruit (34%, n = 32/95).A Phe exchange system to allocate dietary Phe was used by 52% (n = 49/95) of centres predominantly from Northern and Southern Europe and 48% (n = 46/95) calculated most Phe containing food sources (all centres in Eastern Europe and the majority from Germany and Austria). Some centres used a combination of both methods.A second stage Phe-free L-amino acid supplement containing a higher protein equivalent was introduced by 41% (n = 39/95) of centres at infant age 26–36 weeks (mainly from Germany, Austria, Northern and Eastern Europe) and 37% (n = 35/95) at infant age > 1y mainly from Southern Europe. 53% (n = 50/95) of centres recommended a second stage Phe-free L-amino acid supplement in a spoonable or semi-solid form. Conclusions: Weaning strategies vary throughout European PKU centres. There is evidence to suggest that different infant weaning strategies may influence longer term adherence to the PKU diet or acceptance of Phe-free L-amino acid supplements; rendering prospective long-term studies important. It is essential to identify an effective weaning strategy that reduces caregiver burden but is associated with acceptable dietary adherence and optimal infant feeding development. Keywords: Weaning, Infant, Phenylketonuria, Phenylalanine, Phe-free infant formula

Background: In infants with phenylketonuria (PKU), dietary management is based on lowering and titrating phenylalanine (Phe) intake from breast milk or standard infant formula in combination with a Phe-free infant formula in order to maintain blood Phe levels within target range. Professionals use different methods to feed infants with PKU and our survey aimed to document practices across Europe. Methods: We sent a cross sectional, survey monkey® questionnaire to European health professionals working in IMD. It contained 31 open and multiple-choice questions. The results were analysed according to different geographical regions. Results: Ninety-five centres from 21 countries responded. Over 60% of centres commenced diet in infants by age 10 days, with 58% of centres implementing newborn screening by day 3 post birth. At diagnosis, infant hospital admission occurred in 61% of metabolic centres, mainly in Eastern, Western and Southern Europe. Breastfeeding fell sharply following diagnosis with only 30% of women still breast feeding at 6 months.53% of centres gave pre-measured Phe-free infant formula before each breast feed and 23% alternated breast feeds with Phe-free infant formula. With standard infant formula feeds, measured amounts were followed by Phe-free infant formula to satiety in 37% of centres (n = 35/95), whereas 44% (n = 42/95) advised mixing both formulas together. Weaning commenced between 17 and 26 weeks in 85% centres, ≥26 weeks in 12% and

The adoption of artificial intelligence (AI) in medical imaging requires careful evaluation of machine-learning algorithms. We propose the use of a "deep virtual clinical trial" (DeepVCT) method to effectively evaluate the performance of AI algorithms. In this paper, DeepVCTs have been proposed to elucidate limitations of AI applications and predictions of clinical outcomes, avoiding biases in study designs. The DeepVCT method was used to evaluate the performance of nnU-Net models in assessing volumetric breast density (VBD) from digital breast tomosynthesis (DBT) images. In total, 2,010 anatomical breast models were simulated. Projections were simulated using the acquisition geometry of a clinical DBT system. The projections were reconstructed using 0.1, 0.2, and 0.5 mm plane spacing. nnU-Net models were developed using the center-most planes of the reconstructions with the respective ground-truth. The results show that the accuracy of the nnU-Net improves significantly with DBT images reconstructed with 0.1 mm plane spacing (78.4×205.3×40.1 mm 3 ). The segmentations resulted in Dice values up to 0.84 with area under the receiver operating characteristic curve of 0.92. The optimization of plane spacing for VBD assessment was used as an exemplar of a DeepVCT application, allowing us to interpret better the input parameters and outcomes of the nnU-Net. Thus, DeepVCTs can provide a plethora of evidence to predict the efficacy of these algorithms using large-scale simulation-based data., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Psidium brownianum Mart is reported in the literature by antinociceptive and antioxidant activities, indicating that this species' secondary metabolites might be used to control inflammatory processes. The present study aimed to characterize the topical antiedematogenic activity of the essential oil of Psidium brownianum Mart. (OEPB) in ear edema models by different inflammatory agents. Female Swiss mice (25-35 g) and Wistar albino rats (200-300 g) were used throughout tests (n=6/group) on acute or chronic edema models induced by single and multiple topical applications. The OEPB is administered topically pure or at a concentration of 100 or 200 mg/mL. The antiedematogenic mechanism of OEPB was analyzed by administering capsaicin, arachidonic acid, histamine, and phenol at the best effective dose (200 mg/mL). The results showed a significant reduction of edema-induced single (28.87 %) and multiple (50.13 %) applications of croton oil compared to the negative control group. Regarding potential mechanisms of action, OEPB (200 mg/mL) inhibited the development of edema triggered by capsaicin (29.95 %), arachidonic acid (22.66 %), phenol (23.35 %), and histamine (75.46 %), suggesting an interference with the histaminergic pathway. These results indicate that OEPB presents a topical antiedematogenic effect in acute and chronic murine models, possibly interfering with inflammatory pathways triggered by mediators such as histamine., (© 2024 Wiley‐VHCA AG, Zurich, Switzerland.)

Inflammation is a protective response of the body potentially caused by microbial, viral, or fungal infections, tissue damage, or even autoimmune reactions. The cardinal signs of inflammation are consequences of immunological, biochemical, and physiological changes that trigger the release of pro-inflammatory chemical mediators at the local of the injured site thus, increasing blood flow, vascular permeability, and leukocyte recruitment. The aim of this study is to give an overview of the inflammatory process, focusing on chemical mediators. The literature review was based on a search of journals published between the years 2009 and 2023, regarding the role of major chemical mediators in the inflammatory process and current studies in pathogenesis, diagnosis, and therapy. Some of the recent contributions in the study of inflammatory pathologies and their mediators, including cytokines and chemokines, the kinin system, free radicals, nitric oxide, histamine, cell adhesion molecules, leukotrienes, prostaglandins and the complement system and their role in human health and chronic diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Glutaric acidemia type 1 (GA1) is a rare autosomal recessive disorder characterized by a deficiency of glutaryl-CoA dehydrogenase, resulting in the accumulation of glutaric acid (GA), 3-hydroxyglutaric acid, and glutarylcarnitine, especially in the brain. GA1-affected children are clinically characterized by macrocephaly. Neurological abnormalities usually appear between 6 and 18 months of age, often triggered by a catabolic event. On the other hand, several biochemically affected individuals may remain asymptomatic or experience an insidious onset of mild neurological abnormalities., Methods: Retrospective study of GA1 patients followed at a Portuguese Hereditary Metabolic Disease Center, to characterize the phenotypic and genotypic variations associated with GA1. Therefore, we analyzed the clinical, neuroradiological, biochemical, and genetic information from 14 patients., Results: 14 patients (four months-27 years old) were identified in the last 26 years, 9 were male, 1 was from a consanguineous family. 11 were diagnosed by newborn screening (NBS), and 3 identified following clinical symptoms (later diagnosed, LD). There were 3 phenotypic presentations: 6 asymptomatic, 3 with a motor disability after encephalopathic crisis (EC), and 5 with insidious onset. Acute EC occurred in 1/3 of the LD patients and in 2/11 NBS-identified patients. About urinary GA concentrations: 5 were low excretors (LE), 9 were high excretors (HE). All LE showed symptoms, and 2 had EC. Concerning HE, 3 showed symptoms and 1 had EC. GCDH analysis showed: 6 compound heterozygotes and 8 homozygotes. most frequent variant was c.1204C>T (p.R402W). All of them received appropriate therapy from the time of diagnosis, with a mean age of 23.3 months in LD patients and 13.3 days in NBS-identified patients., Conclusion: The outcomes were different between the two groups: all the LD patients presented motor dysfunction however in the NBS-identified patients only 5 developed this symptom. Patients identified by NBS had better outcomes showing that NBS enables an early diagnosis, and treatment, and consequently improves the clinical outcomes for these patients. No correlation was observed with clinical phenotype between LE and HE, as both groups can suffer the most severe neurological manifestations. These conclusions are in agreement with previous cohorts described in the literature., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The shortage of physicians in rural and underserved areas is an obstacle to the implementation of Universal Health Coverage (UHC). We carried out a systematic review to analyze the effectiveness of initiatives in medical education aimed to increase the supply of physicians in rural or underserved areas. We searched for studies published between 1999 and 2019 in six databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Interventional or observational controlled studies were defined as inclusion criteria. A total of 955 relevant unique records were selected for inclusion, which resulted in the identification of 17 articles for analysis. The admission of students from rural areas associated with a rural curriculum represented 52.95% of the interventions. Medical practice after graduation in rural or underserved areas was the most evaluated outcome, representing 12 publications (70.59%). Participants of these educational initiatives were more likely to work in rural or underserved areas or to choose family medicine, with significant differences between the groups in 82.35% of the studies. Educational strategies in undergraduate and medical residencies are effective. However, it is necessary to expand these interventions to ensure the supply of physicians in rural or urban underserved areas.

This study assesses the effectiveness of policies to expand access to higher education in reducing inequities in the profile of graduates from medical courses in Brazil. This work consists of a cross-sectional study using data from the 2018 Higher Education Census. Analyses were carried out to identify the association between being a beneficiary of the Quota Law, the University for All Program, or the Student Financing Fund and three markers: born in a small-sized municipality, being non-white, or having attended high school in a public school. Analyses were performed using Pearson's chi-square test, and multivariate analysis was conducted using Poisson regression. A significant association was found between being a beneficiary of these policies and being a non-white graduate, who was born in a small town and who had studied in a public high school. All policies presented adjusted Prevalence Ratio (PR), which demonstrated an association with statistical significance. The Quota Law was the most effective policy, with RP=1.92 for non-white graduates, RP=6.66 for having studied in a public high school, and RP=1.08 for being born in a small town. Despite these results, these groups remain underrepresented in medical courses and in the workforce.

Introduction  The technology regarding bone-anchored hearing devices has been advancing. Nevertheless, complications are still often reported, which can impair treatment adherence and lead to discontinuation of use. There is a lack of studies conducted in tropical countries, where complications can be even greater, as well as standardized protocols for selection, indication and evaluation. Objective  To characterize implanted patients from a Brazilian public institution and describe the medical and audiological assessment protocols to which they were submitted during the selection process and in the follow-up after surgery. Method  An observational, cross-sectional study evaluating the medical records of patients with hearing loss and ear malformations and describing the care protocol through which they were treated. Results  The medical records of 15 patients were reviewed: 6 received transcutaneous implants, and 9, percutaneous implants; 9 patients reported some type of skin lesion, 2 reported pain on the follow-up visit, and 3 had osseointegration failure. The time between surgery and activation ranged from 2 to 9 months. The median scores on the sentences, Sentences in Noise and Monosyllable tests were 100%, 60% and 80%, respectively. Conclusion  It was possible to characterize the patients who received implants at the institution. The patients performed well in silence and had greater difficulty in noise. Even patients who had complications did not complain about the audibility and sound quality. It is essential to develop a model and to standardize the assessment and follow-up methods aimed at the benefit of users of bone-anchored hearing devices, as well as to enable the technico-scientific development in this field., Competing Interests: Conflict of Interests The authors have no conflict of interests to declare., (Fundação Otorrinolaringologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Objective: Identify risk factors for microcephaly and evaluate historical trends of microcephaly and arboviruses to recognize patterns and anomalies that indicate the beginning of the microcephaly epidemic associated with Zika infection., Methods: The head circumferences of 62,298 newborns was analyzed to identify cases of microcephaly between 2014 and 2017. We compared the groups of newborns with normal head circumferences and those with microcephaly to identify risk factors. A time series with the incidences of microcephaly was analyzed to assess the appearance of anomalous values in order to identify the beginning of the microcephaly epidemic. Data on the incidence of dengue fever was used to develop a control chart, aiming to identify changes in incidence and seasonality that could suggest the circulation of a new arbovirus., Findings: Premature newborns, children of mothers under 20 years of age and those born in 2014 and 2015 had a higher risk of microcephaly. Three quarters with anomalous incidences of microcephaly were identified, the first in 2014 and the others in 2015. The dengue fever epidemic curve in 2013 shows persistence of high incidences in atypical periods, suggesting the entry of a new virus in the 3rd and 4th quarters., Conclusions: These findings represent epidemiological evidence of the existence of cases of Zika virus between the 2nd quarter of 2013 and the beginning of 2014. The results add new elements to understanding the Zika virus epidemic in the Americas., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Shortages and inequitable distribution of physicians is an obstacle to move towards Universal Health Coverage, especially in low-income and middle-income countries. In Brazil, expansion of medical school enrollment, curricula changes and recruitment programs were established to increase the number of physicians in underserved areas. This study seeks to analyze the impact of these measures in reduce inequities in access to medical education and physicians' distribution., Methods: This is an observational study that analyzes changes in the number of undergraduate medical places and number of physicians per inhabitants in different areas in Brazil between the years 2010 and 2018. Data regarding the number of undergraduate medical places, number and the practice location of physicians were obtained in public databases. Municipalities with less than 20,000 inhabitants were considered underserved areas. Data regarding access to antenatal visits were analyzed as a proxy for impact in access to healthcare., Results: From 2010 to 2018, 19,519 new medical undergraduate places were created which represents an increase of 120.2%. The increase in the number of physicians engaged in the workforce throughout the period was 113,702 physicians, 74,771 of these physicians in the Unified Health System. The greatest increase in the physicians per 1000 inhabitants ratio in the municipalities with the smallest population, the lowest Gross Domestic Product per capita and in those located in the states with the lowest concentration of physicians occurred in the 2013-2015 period. Increase in physician supply improved access to antenatal care., Conclusions: There was an expansion in the number of undergraduate medical places and medical workforce in all groups of municipalities assessed in Brazil. Medical undergraduate places expansion in the federal public schools was more efficient to reduce regional inequities in access to medical education than private sector expansion. The recruitment component of More Doctors for Brazil Program demonstrated effectiveness to increase the number of physicians in underserved areas. Our results indicate the importance of public policies to face inequities in access to medical education and physician shortages and the necessity of continuous assessment during the period of implementation, especially in the context of political and economic changes.

This research evaluated the anxiolytic and antidepressant-like effects of a hydroethanolic extract from the leaves of Annona coriacea (EHFAC) and caffeic acid (CA). Mice were intraperitoneally treated with saline, EHFAC (1, 10, 20 mg/kg) or CA (0.15 mg/kg) and subject to the elevated plus-maze, open field, rota-rod, forced swimming and reserpine-induced akinesia tests. Pro-convulsant and anticholinergic effects were also evaluated. EHFAC presented anxiolytic-like effect on the elevated plus-maze, which was partially reversed by flumazenil. A similar effect was observed with CA. In the forced swimming test, EHFAC and CA reduced the immobility time of mice; such effect was potentiated when EHFAC or CA were associated with imipramine, bupropion and fluoxetine. The antidepressant-like effect was reinforced as EHFAC partially reversed the reserpine-induced akinesia. In addition, a pre-treatment with EHFAC and CA did not decrease the latency to 1st seizure of animals that received a sub-convulsive dose of PTZ, nor reduced the intensity of oxotremorine-induced tremors. Taken together, the results indicate that EHFAC and CA have anxiolytic and antidepressant-like effects, which involve important neurotransmitter systems, such as GABAergic and monoaminergic ones, being devoid of side effects, commonly associated with classical psychotropic drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: In phenylketonuria (PKU), weaning is considered more challenging when compared to feeding healthy infants. The primary aim of weaning is to gradually replace natural protein from breast milk or standard infant formula with solids containing equivalent phenylalanine (Phe). In addition, a Phe-free second stage L-amino acid supplement is usually recommended from around 6 months to replace Phe-free infant formula. Our aim was to assess different weaning approaches used by health professionals across Europe., Methods: A cross sectional questionnaire (survey monkey®) composed of 31 multiple and single choice questions was sent to European colleagues caring for inherited metabolic disorders (IMD). Centres were grouped into geographical regions for analysis., Results: Weaning started at 17-26 weeks in 85% ( n  = 81/95) of centres, >26 weeks in 12% ( n  = 11/95) and < 17 weeks in 3% ( n  = 3/95). Infant's showing an interest in solid foods, and their age, were important determinant factors influencing weaning commencement. 51% ( n  = 48/95) of centres introduced Phe containing foods at 17-26 weeks and 48% ( n  = 46/95) at >26 weeks. First solids were mainly low Phe vegetables (59%, n  = 56/95) and fruit (34%, n  = 32/95).A Phe exchange system to allocate dietary Phe was used by 52% ( n  = 49/95) of centres predominantly from Northern and Southern Europe and 48% (n = 46/95) calculated most Phe containing food sources (all centres in Eastern Europe and the majority from Germany and Austria). Some centres used a combination of both methods.A second stage Phe-free L-amino acid supplement containing a higher protein equivalent was introduced by 41% ( n  = 39/95) of centres at infant age 26-36 weeks (mainly from Germany, Austria, Northern and Eastern Europe) and 37% ( n  = 35/95) at infant age > 1y mainly from Southern Europe. 53% ( n  = 50/95) of centres recommended a second stage Phe-free L-amino acid supplement in a spoonable or semi-solid form., Conclusions: Weaning strategies vary throughout European PKU centres. There is evidence to suggest that different infant weaning strategies may influence longer term adherence to the PKU diet or acceptance of Phe-free L-amino acid supplements; rendering prospective long-term studies important. It is essential to identify an effective weaning strategy that reduces caregiver burden but is associated with acceptable dietary adherence and optimal infant feeding development.

Background: In infants with phenylketonuria (PKU), dietary management is based on lowering and titrating phenylalanine (Phe) intake from breast milk or standard infant formula in combination with a Phe-free infant formula in order to maintain blood Phe levels within target range. Professionals use different methods to feed infants with PKU and our survey aimed to document practices across Europe., Methods: We sent a cross sectional, survey monkey® questionnaire to European health professionals working in IMD. It contained 31 open and multiple-choice questions. The results were analysed according to different geographical regions., Results: Ninety-five centres from 21 countries responded. Over 60% of centres commenced diet in infants by age 10 days, with 58% of centres implementing newborn screening by day 3 post birth. At diagnosis, infant hospital admission occurred in 61% of metabolic centres, mainly in Eastern, Western and Southern Europe. Breastfeeding fell sharply following diagnosis with only 30% of women still breast feeding at 6 months.53% of centres gave pre-measured Phe-free infant formula before each breast feed and 23% alternated breast feeds with Phe-free infant formula. With standard infant formula feeds, measured amounts were followed by Phe-free infant formula to satiety in 37% of centres ( n  = 35/95), whereas 44% ( n  = 42/95) advised mixing both formulas together. Weaning commenced between 17 and 26 weeks in 85% centres, ≥26 weeks in 12% and < 17 weeks in 3%., Discussion: This is the largest European survey completed on PKU infant feeding practices. It is evident that practices varied widely across Europe, and the practicalities of infant feeding in PKU received little focus in the PKU European Guidelines (2017). There are few reports comparing different feeding techniques with blood Phe control, Phe fluctuations and growth. Controlled prospective studies are necessary to assess how different infant feeding practices may influence longer term feeding development.

Caryocar coriaceum Wittm. (Pequi) is found in southern Ceará, where the fruit is used as food and in folk medicine as an anti-inflammatory, and to promote healing. However, little is known about the effects of repeated administration of its oil on the biochemical parameters of the blood. This work aimed to evaluate the effects Caryocar coriaceum fixed oil (OFCC); on the lipid profiles of healthy mice, on dyslipidemia induced by tyloxapol, and to study its anti-inflammatory effect both in vivo and in vitro. The results revealed significant reduction in total serum cholesterol and triglycerides, and an increase in HDL-C. The paw edema (induced by carrageenan) and myeloperoxidase (MPO), in polymorphonuclear culture cells, was reduced at all dose levels. Results demonstrated that Caryocar coriaceum's fix oil present anti-inflammatory activity and, for the first time describe the hypolipidemic effects, supporting its traditional use and suggest that present a potential cardioprotective effect., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The purpose of this work was to verify in vitro adherence of E. corrodens and S. oralis to the surface of tongue piercings made of surgical steel, titanium, Bioplast, and Teflon. For this, 160 piercings were used for the count of Colony Forming Units (CFU) and 32 piercings for analysis under scanning electron microscopy. Of these, 96 (24 of each type) were individually incubated in 5 mL of BHI broth and 50  μ L of inoculum at 37°C/24 h. The other 96 piercings formed the control group and were individually incubated in 5 mL of BHI broth at 37°C/24 h. Plates were incubated at 37°C/48 h for counting of CFU/mL and data were submitted to statistical analysis ( p value <0.05). For E. corrodens , difference among types of material was observed ( p < 0.001) and titanium and surgical steel showed lower bacterial adherence. The adherence of S. oralis differed among piercings, showing lower colonization ( p < 0.007) in titanium and surgical steel piercings. The four types of piercings were susceptible to colonization by E. corrodens and S. oralis , and bacterial adhesion was more significant in those made of Bioplast and Teflon. The piercings presented bacterial colonies on their surface, being higher in plastic piercings probably due to their uneven and rough surface., Competing Interests: The authors have no potential competing interests.