Casein glycomacropeptide in phenylketonuria: does it bring clinical benefit?

PURPOSE OF REVIEW: Casein glycomacropeptide (CGMP) is a milk-derived bioactive sialyated phosphorylated peptide with distinctive nutritional and nutraceutical properties, produced during the cheese making process. It comprises 20-25% of total protein in whey products. CGMP is low in phenylalanine (Phe) and provides an alternative to Phe-free amino acids as a source of protein equivalent for patients with phenylketonuria (PKU). The amino acid sequence of CGMP is adapted by adding the amino acids histidine, leucine, tyrosine, arginine and tryptophan to enable its suitability in PKU. CGMP has potential antibacterial, antioxidative, prebiotic, remineralizing, digestion /metabolism and immune-modulating properties. The aim of this review is to assess the evidence for the role of CGMP in the management of PKU. RECENT FINDINGS: In PKU, there is no agreement concerning the amino acid composition of CGMP protein substitutes and consequently the nutritional composition varies between products. Although there is evidence in patients or animal models that CGMP has possible beneficial effects on gut microbiota and bone health, the results are inconclusive. Data on kinetic advantage is limited. Most studies report an increase in blood Phe levels with CGMP. Appropriate adaptations and reduction of dietary Phe intake should be made to compensate for the residual Phe content of CGMP, particularly in children. Data from short term studies indicate improved palatability of CGMP when compared to Phe-free amino acids. SUMMARY: In PKU, CGMP with supplementary amino acids, offers a safe low Phe nitrogen source. Current scientific evidence is unconvincing about its bioactive advantage in PKU. Further longitudinal research is necessary.

Natural Protein Intake in Children with Phenylketonuria: Prescription vs. Actual Intakes.

In phenylketonuria (PKU), an important component of the UK dietary management system is a 50 mg phenylalanine (Phe)/1 g protein exchange system used to allocate the Phe/natural protein intakes according to individual patient tolerance. Any foods containing protein ≤ 0.5 g/100 g or fruits/vegetables containing Phe ≤ 75 mg/100 g are allowed without measurement or limit. In children with PKU, we aimed to assess the difference between the prescribed natural protein intake and their actual consumed intake, and to calculate the natural protein/Phe intake from foods given without measurement or restriction. Over a 6-month duration, three one-day diet diaries were collected every month by caregivers of children with PKU at the beginning of a follow-up study. Dietary intakes of Phe, as well as natural and total protein intakes, were calculated using Nutritics® (v5.09). Weekly blood Phe spots were collected by caregivers. The target blood Phe level was ≤360 µmol/L for ages up to 12 years and ≤600 µmol/L for ages ≥12 years. Sixteen early treated children (69% females) with PKU were recruited. The median age was 11 years (range: 9-13), and most had classical PKU (n = 14/16). A median of 18 (range 12-18) one-day diaries and 22 blood spots were analysed for each subject over 6 months. The median prescribed natural protein was 6 g/day (range: 3-27), but when calculated, the actual median intake from all foods consumed was 10 g/day (range: 4-37). The median prescribed Phe was 300 mg/day (range: 150-1350), but the actual median intake was 500 mg/day (range: 200-1850). The median difference between the prescribed and actual natural protein daily intakes was +4 g/day (range: -2.5 to +11.5), with a median percentage increase of 40% for natural protein/Phe intake (p < 0.001). The median blood Phe level was 250 µmol/L (range 20-750), with 91% of blood Phe levels within the target range. Only one patient (11 years) had less than 75% of their blood Phe levels within the target range. The UK Phe exchange system provides flexibility in the dietary management of PKU. With this method, the actual natural protein intake was 167% higher than the prescribed amount. Although this led to a variable daily protein intake, the majority of children (n = 15/16) experienced no deterioration in their metabolic control.

Casein glycomacropeptide in phenylketonuria: does it bring clinical benefit?

PURPOSE OF REVIEW: Casein glycomacropeptide (CGMP) is a milk-derived bioactive sialyated phosphorylated peptide with distinctive nutritional and nutraceutical properties, produced during the cheese making process. It comprises 20-25% of total protein in whey products. CGMP is low in phenylalanine (Phe) and provides an alternative to Phe-free amino acids as a source of protein equivalent for patients with phenylketonuria (PKU). The amino acid sequence of CGMP is adapted by adding the amino acids histidine, leucine, tyrosine, arginine and tryptophan to enable its suitability in PKU. CGMP has potential antibacterial, antioxidative, prebiotic, remineralizing, digestion /metabolism and immune-modulating properties. The aim of this review is to assess the evidence for the role of CGMP in the management of PKU. RECENT FINDINGS: In PKU, there is no agreement concerning the amino acid composition of CGMP protein substitutes and consequently the nutritional composition varies between products. Although there is evidence in patients or animal models that CGMP has possible beneficial effects on gut microbiota and bone health, the results are inconclusive. Data on kinetic advantage is limited. Most studies report an increase in blood Phe levels with CGMP. Appropriate adaptations and reduction of dietary Phe intake should be made to compensate for the residual Phe content of CGMP, particularly in children. Data from short term studies indicate improved palatability of CGMP when compared to Phe-free amino acids. SUMMARY: In PKU, CGMP with supplementary amino acids, offers a safe low Phe nitrogen source. Current scientific evidence is unconvincing about its bioactive advantage in PKU. Further longitudinal research is necessary.

Phenylalanine Tolerance over Time in Phenylketonuria: A Systematic Review and Meta-Analysis.

In phenylketonuria (PKU), natural protein tolerance is defined as the maximum natural protein intake maintaining a blood phenylalanine (Phe) concentration within a target therapeutic range. Tolerance is affected by several factors, and it may differ throughout a person's lifespan. Data on lifelong Phe/natural protein tolerance are limited and mostly reported in studies with low subject numbers. This systematic review aimed to investigate how Phe/natural protein tolerance changes from birth to adulthood in well-controlled patients with PKU on a Phe-restricted diet. Five electronic databases were searched for articles published until July 2020. From a total of 1334 results, 37 articles met the eligibility criteria (n = 2464 patients), and 18 were included in the meta-analysis. The mean Phe (mg/day) and natural protein (g/day) intake gradually increased from birth until 6 y (at the age of 6 months, the mean Phe intake was 267 mg/day, and natural protein intake was 5.4 g/day; at the age of 5 y, the mean Phe intake was 377 mg/day, and the natural protein intake was 8.9 g/day). However, an increase in Phe/natural protein tolerance was more apparent at the beginning of late childhood and was >1.5-fold that of the Phe tolerance in early childhood. During the pubertal growth spurt, the mean natural protein/Phe tolerance was approximately three times higher than in the first year of life, reaching a mean Phe intake of 709 mg/day and a mean natural protein intake of 18 g/day. Post adolescence, a pooled analysis could only be performed for natural protein intake. The mean natural protein tolerance reached its highest (32.4 g/day) point at the age of 17 y and remained consistent (31.6 g/day) in adulthood, but limited data were available. The results of the meta-analysis showed that Phe/natural protein tolerance (expressed as mg or g per day) increases with age, particularly at the beginning of puberty, and reaches its highest level at the end of adolescence. This needs to be interpreted with caution as limited data were available in adult patients. There was also a high degree of heterogeneity between studies due to differences in sample size, the severity of PKU, and target therapeutic levels for blood Phe control.

Preliminary Data on Free Use of Fruits and Vegetables Containing Phenylalanine 76-100 mg/100 g of Food in 16 Children with Phenylketonuria: 6 Months Follow-Up.

In phenylketonuria (PKU), a previous intervention study assessing the patients ability to tolerate fruits and vegetables containing phenylalanine 76-100 mg/100 g without limit or measurement, found that an extra 50 mg/day phenylalanine, but not 100 mg/day, was tolerated from these fruits and vegetables. In a further 6-month extension study, we examined the effect of the 'free' use of this group of fruits and vegetables on blood phenylalanine control. For 6 months, the patients ate fruits and vegetables containing phenylalanine 76-100 mg/100 g without limit or measurement. Three-day diet diaries and the patients' weights were collected monthly. Blood phenylalanine spots were collected weekly aiming for blood phenylalanine levels <360 µmol/L. Retrospective blood phenylalanine was collected 6 months pre-trial. All 16 patients (69% females) from the intervention study took part in the extension study. Most of the patients (n = 14/16) had classical PKU with a median age of 10.5 years (range: 6-13). There was no statistically significant difference in the median blood phenylalanine pre-study (270, range: 50-760 µmol/L) compared to the 6-month extension study (250, range: 20-750 µmol/L) (p= 0.4867). The patients had a median of 21 and 22 bloodspots, pre- and post-trial, respectively. In the extension study, the patients had an actual mean intake of 11 g/day (4-37) natural protein and 65 g/day (60-80) protein equivalent from a protein substitute. The mean phenylalanine intake was 563 mg/day (200-1850) with only 19 mg/day (0-146) phenylalanine from fruits and vegetables containing phenylalanine 76-100 mg/100 g. The weight z-scores remained unchanged (1.52 vs. 1.60, p = 0.4715). There was no adverse impact on blood phenylalanine control when fruits and vegetables containing phenylalanine 76-100 mg/100 g were eaten without limit or measurement. However, the fruits and vegetable portion sizes eaten were small (60 g/week). Further longitudinal work is necessary to examine the 'free' use of fruits and vegetables containing phenylalanine 76-100 mg/100 g on metabolic control in patients with PKU.

Factors Associated with Readmission within 30 Days after Discharge and In-Hospital Mortality after Proximal Femoral Fracture Surgery in the Elderly: Retrospective Cohort.

Objective To evaluate the factors associated with readmission within 30 days after discharge (R30) and in-hospital mortality (IHM) in elderly patients undergoing proximal femur fracture surgery (PFF). Methods Retrospective cohort with data from 896 medical records of elderly (≥ 60 years) patients submitted to PFF surgery in a Brazilian hospital between November 2014 and December, 2019. The patients included were followed-up from the date of hospitalization for surgery up to 30 days after discharge. As independent variables, we evaluated gender, age, marital status, pre- and postoperative hemoglobin (Hb), international normalized ratio, time of hospitalization related to the surgery, door-surgery time, comorbidities, previous surgeries, use of medications, and the American Society of Anesthesiologists (ASA) score. Results The incidence of R30 was 10.2% (95% confidence interval [CI]: 8.3-12.3%), and the incidence of IHM was 5.7% (95%CI: 4.3-7.4%). Regarding R30, hypertension (odds ratio [OR]: 1.71; 95%CI: 1.03-2.96), and regular use of psychotropic drugs (OR: 1.74; 95%CI: 1.12-2.72) were associated in the adjusted model. In the case of IHM, higher chances were associated with chronic kidney disease (CKD) (OR: 5.80; 95%CI: 2.64-12.31), longer hospitalization time (OR: 1.06; 95%CI: 1.01-1.10), and R30 (OR: 3.60; 95%CI: 1.54-7.96). Higher preoperative Hb values were associated with a lower chance of mortality (OR: 0.73; 95%CI: 0.61-0.87). Conclusion Findings suggest that the occurrence of these outcomes is associated with comorbidities, medications, and Hb.

Parent's Perception of the Types of Support Given to Families with an Infant with Phenylketonuria.

BACKGROUND: A diagnosis of phenylketonuria (PKU) in an infant is a devastating and overwhelming event for their parents. Providing appropriate information and support is paramount, especially at the beginning of a child's life. Investigating if parents are receiving the right support is important for continued care. METHODOLOGY: An online survey was distributed to explore parents' perceptions of current support and information provided by their healthcare provider and to rate sources of other support (n = 169 participants). RESULTS: Dietitians received the highest (85%) rate of "very helpful" support. Overall, parents found Facebook to be helpful for support but had mixed reactions when asked if healthcare professionals (HCPs) should provide advice as part of the groups. When rating the most effective learning methods, the top three were 1:1 teaching sessions (n = 109, 70%), picture books (n = 73, 50%), and written handouts (n = 70, 46%). CONCLUSION: Most parents are happy with the support and information they receive from their dietitian but required more support from other HCPs. Facebook groups provide parents with the social support that HCPs and their family may be unable to offer, suggesting a place for social media in future PKU care.

Factors Associated with Readmission within 30 Days after Discharge and In-Hospital Mortality after Proximal Femoral Fracture Surgery in the Elderly: Retrospective Cohort / Fatores associados à reinternação em até 30 dias após a alta e à mortalidade intra-hospitalar após cirurgia por fratura do fêmur proximal em idosos: coorte retrospectiva

Abstract Objective To evaluate the factors associated with readmission within 30 days after discharge (R30) and in-hospital mortality (IHM) in elderly patients undergoing proximal femur fracture surgery (PFF). Methods Retrospective cohort with data from 896 medical records of elderly (≥ 60 years) patients submitted to PFF surgery in a Brazilian hospital between November 2014 and December, 2019. The patients included were followed-up from the date of hospitalization for surgery up to 30 days after discharge. As independent variables, we evaluated gender, age, marital status, pre- and postoperative hemoglobin (Hb), international normalized ratio, time of hospitalization related to the surgery, door-surgery time, comorbidities, previous surgeries, use of medications, and the American Society of Anesthesiologists (ASA) score. Results The incidence of R30 was 10.2% (95% confidence interval [CI]: 8.3-12.3%), and the incidence of IHM was 5.7% (95%CI: 4.3-7.4%). Regarding R30, hypertension (odds ratio [OR]: 1.71; 95%CI: 1.03-2.96), and regular use of psychotropic drugs (OR: 1.74; 95%CI: 1.12-2.72) were associated in the adjusted model. In the case of IHM, higher chances were associated with chronic kidney disease (CKD) (OR: 5.80; 95%CI: 2.64-12.31), longer hospitalization time (OR: 1.06; 95%CI: 1.01-1.10), and R30 (OR: 3.60; 95%CI: 1.54-7.96). Higher preoperative Hb values were associated with a lower chance of mortality (OR: 0.73; 95%CI: 0.61-0.87). Conclusion Findings suggest that the occurrence of these outcomes is associated with comorbidities, medications, and Hb.

Resumo Objetivo Avaliar os fatores associados à reinternação em até 30 dias após a alta (R30) e à mortalidade intra-hospitalar (MIH) em idosos submetidos a cirurgia por fratura do fêmur proximal (FFP). Métodos Coorte retrospectiva com dados de 896 prontuários de idosos (≥ 60 anos) submetidos a cirurgia de FFP em hospital brasileiro, no período entre novembro de 2014 a dezembro de 2019. Os pacientes incluídos foram acompanhados desde a data de internação para a cirurgia até 30 dias após a alta. Como variáveis independentes, foram avaliados o sexo, idade, estado civil, hemoglobina (Hb) pré e pós-operatória, razão normalizada internacional, tempo da internação relacionada à cirurgia, tempo porta cirurgia, comorbidades, cirurgias prévias, uso de medicamentos e escore da American Society of Anesthesiologists (ASA). Resultados A incidência de R30 foi de 10,2% (intervalo de confiança [IC] 95%: 8,3-12,3%) e a de MIH foi 5,7% (IC95%: 4,3-7,4%). Referente a R30, no modelo ajustado, associaram-se ter hipertensão (odds ratio [OR]: 1,71; IC95%: 1,03-2,96), uso regular de medicamentos psicotrópicos (OR: 1,74; IC95%: 1,12-2,72). Tratando-se da MIH, maiores chances estiveram associadas à doença renal crônica (DRC) (OR: 5,80; IC95%: 2,64-12,31), maior tempo de internação (OR: 1,06; IC95%: 1,01-1,10) e R30 (OR: 3,60; IC95%: 1,54-7,96). Maiores valores de Hb pré-operatória associaram-se à menor chance de mortalidade (OR: 0,73; IC95%: 0,61-0,87). Conclusão Os achados sugerem que a ocorrência destes desfechos está associada à comorbidades, medicamentos e Hb.

Phenylalanine free infant formula in the dietary management of phenylketonuria.

BACKGROUND: Phenylalanine-free infant formula is an essential source of safe protein in a phenylalanine restricted diet, but its efficacy is rarely studied. We report a multicentre, open, longitudinal, prospective intervention study on a phenylalanine-free infant formula (PKU Start: Vitaflo International Ltd.). RESULTS: This was a 2-part study: part I (28 days short term evaluation) and part II (12 months extension). Data was collected on infant blood phenylalanine concentrations, dietary intake, growth, and gastrointestinal tolerance. Ten infants (n = 8 males, 80%), with a median age of 14 weeks (range 4-36 weeks) were recruited from 3 treatment centres in the UK. Nine of ten infants completed the 28-day follow-up (one caregiver preferred the usual phenylalanine-free formula and discontinued the study formula after day 14) and 7/9 participated in study part II. The phenylalanine-free infant formula contributed a median of 57% (IQR 50-62%) energy and 53% (IQR 33-66%) of total protein intake from baseline to the end of the part II extension study. During the 12-month follow-up, infants maintained normal growth and satisfactory blood phenylalanine control. Any early gastrointestinal symptoms (constipation, colic, vomiting and poor feeding) improved with time. CONCLUSION: The study formula was well tolerated, helped maintain good metabolic control, and normal growth in infants with PKU. The long-term efficacy of phenylalanine-free infant formula should continue to be observed and monitored.

Associations of Hearing Loss and Hearing Aid Use With Cognition, Health-Related Quality of Life, and Depressive Symptoms.

ObjectivesDetermine associations of hearing loss (HL) and hearing aid (HA) use with cognition, health-related quality of life (HRQoL), and depressive symptoms. Methods: Participants were from the Epidemiology of Hearing Loss Study or Beaver Dam Offspring Study. HL was defined as pure-tone average (.5-4.0 kHz) > 25 dB. A principal component analysis of 5 cognitive tasks measured cognition. The SF-12 measured mental and physical HRQoL. The Centers for Epidemiological Studies Depression Scale measured depressive symptoms (score ≥ 16). Regression models returned beta (B) coefficients or odds ratios (OR) with 95% confidence intervals. Results: This study included 3574 participants. HL (vs. none) was associated with poorer cognition (B-.12 [-.18, -.06]), mental (B-.99 [-1.65, -.33]) and physical (B-.76 [-1.50, -.03]) HRQoL, and increased odds of depressive symptoms (OR 1.49 [1.16, 1.91]). HA users had better cognition than non-users. Discussion: HL likely impacts cognition and well-being. HA use may have cognitive benefits.

Breast cancer pharmacogenetics: a systematic review.

Breast cancer was declared the most prevalent type of cancer in 2020. Among other factors, treatment response can be affected by genetic polymorphisms - which is the focus of pharmacogenetics - and ethnicity is also a contributing factor in this context. Relevant genes in disease treatment pathways were selected to evaluate treatment response from the pharmacogenetic perspective; polymorphism frequencies and ethnic and continental representation across the available literature were also assessed through a systematic review. The identified associations and gaps have been described in this study with the purpose that, in the future, treatments can be personalized and thus be more effective, safer, and accessible to all.

Association of Central Retinal Arteriolar and Venular Equivalents with Brain-aging and Macular Ganglion Cell-inner Plexiform Layer Thickness.

INTRODUCTION: Neurodegeneration and cognitive decline in aging are growing public health concerns. This study investigates associations between central retinal arteriolar and venular equivalents (CRAE, CRVE) and brain-aging, a sensory and cognitive test composite measure, and macular ganglion cell-inner plexiform layer (mGCIPL) thickness, a biomarker of neurodegeneration. METHODS: Beaver Dam Offspring Study (BOSS) participants are adult children (baseline (2005-2008) age 21-84 years) of the population-based Epidemiology of Hearing Loss Study participants. Follow-up occurred every 5 years. In 2010-2013, fundus photographs were used to measure retinal vessels. A brain-aging score was constructed by principal component analysis using sensorineural and cognitive data. Associations between incident brain-aging and vessel measures were investigated using logistic regression. Associations between CRAE and CRVE and mGCIPL thickness, measured in 2015-2017, were also investigated. RESULTS: Participants (N = 2381; mean age: 53.9 years (SD = 9.8); 54% women) had a mean CRAE and CRVE of 148.8 µm (SD = 14.5) and 221.7 µm (SD = 20.7), respectively. Among those without ocular conditions, wider CRAE was associated with decreased 5-year brain-aging risk (33% per SD CRAE increase). Both vessel measures were independently associated with mGCIPL thickness. The mGCIPL thickness increased by approximately 1.7 µm and 2.0 µm per SD increase in CRAE and CRVE, respectively. DISCUSSION: The association of CRAE with incident brain-aging indicates its potential use as a screening tool among those without eye disease. The associations between CRAE and CRVE and mGCIPL thickness indicate narrower vasculature could affect neuronal health. These associations point to potential usefulness of retinal vessel measurements to identify people at higher risk of sensorineural declines and neurodegeneration.

Suitability and Allocation of Protein-Containing Foods According to Protein Tolerance in PKU: A 2022 UK National Consensus.

Introduction: There is little practical guidance about suitable food choices for higher natural protein tolerances in patients with phenylketonuria (PKU). This is particularly important to consider with the introduction of adjunct pharmaceutical treatments that may improve protein tolerance. Aim: To develop a set of guidelines for the introduction of higher protein foods into the diets of patients with PKU who tolerate >10 g/day of protein. Methods: In January 2022, a 26-item food group questionnaire, listing a range of foods containing protein from 5 to >20 g/100 g, was sent to all British Inherited Metabolic Disease Group (BIMDG) dietitians (n = 80; 26 Inherited Metabolic Disease [IMD] centres). They were asked to consider within their IMD dietetic team when they would recommend introducing each of the 26 protein-containing food groups into a patient's diet who tolerated >10 g to 60 g/day of protein. The patient protein tolerance for each food group that received the majority vote from IMD dietetic teams was chosen as its tolerance threshold for introduction. A virtual meeting was held using Delphi methodology in March 2022 to discuss and agree final consensus. Results: Responses were received from dietitians from 22/26 IMD centres (85%) (11 paediatric, 11 adult). For patients tolerating protein ≥15 g/day, the following foods were agreed for inclusion: gluten-free pastas, gluten-free flours, regular bread, cheese spreads, soft cheese, and lentils in brine; for protein tolerance ≥20 g/day: nuts, hard cheeses, regular flours, meat/fish, and plant-based alternative products (containing 5−10 g/100 g protein), regular pasta, seeds, eggs, dried legumes, and yeast extract spreads were added; for protein tolerance ≥30 g/day: meat/fish and plant-based alternative products (containing >10−20 g/100 g protein) were added; and for protein tolerance ≥40 g/day: meat/fish and plant-based alternatives (containing >20 g/100 g protein) were added. Conclusion: This UK consensus by IMD dietitians from 22 UK centres describes for the first time the suitability and allocation of higher protein foods according to individual patient protein tolerance. It provides valuable guidance for health professionals to enable them to standardize practice and give rational advice to patients.

A relação família-escola nas publicações da ABRAPEE: Estado do conhecimento / Family-school relationship in ABRAPEE'S publications: State of knowledge

O presente artigo consiste em um recorte de monografia, tratando-se de uma investigação sobre como a produção científica relacionada à área da psicologia escolar e educacional, no Brasil, tem abordado a relação família-escola. Foram analisados artigos publicados na Revista Psicologia Escolar e Educacional, da Associação Brasileira de Psicologia Escolar e Educacional, que abordaram, em alguma medida, tal questão, entre os anos de 1996 e 2020. Verificou-se que, em um universo de 692 artigos, apenas 31 discutiram em torno de questões tocantes à relação família-escola. A análise dos artigos revelou que estes foram elaborados em torno de seis eixos temáticos: parceria família-escola; educação infantil; violência; queixa escolar; dificuldades de aprendizagem, e educação especial. Ainda, verificou-se a predominância de pesquisas sobre contextos e amostras singulares e a ausência de discussões no âmbito das políticas públicas.

This article consists of an extract from a monograph, an investigation on how the scientific production related to the area of school and educational psychology, in Brazil, has treated the family-school relationship. It was investigated how scientific production related to the area of school and educational psychology in Brazil has addressed the family-school relationship. Articles published in the Revista Psicologia Escolar e Educacional, from the Associação Brasileira de Psicologia Escolar e Educacional, that addressed this issue between 1996 and 2020, were analyzed. It was found that, in a universe of 692 articles, only 31 discussed issues regarding the family-school relationship. The analysis of the articles allowed the emergence of six thematic axes: family-school partnership; child education; violence; school complaint; learning difficulties and special education. Also, it was verified that there was a prevalence of research on small samples and isolated contexts as well as the absence of discussions within the scope of public policies.

IoT Off-Grid, Data Collection from a Machine Learning Classification Using UAV.

IoT encompasses various objects, technologies, communication standards, sensors, actuators in powered environments, and networked communication. The concept adopted here, IoT off-grid, considers an environment without commercial electricity and commercial internet. Managing various utilities with IoT and collecting the relevant information from this environment is the purpose of this project. It uses machine learning to select relevant data. These data are collected safely using a drone that travels through the off-grid stations. A systematic literature mapping is presented, identifying the state of the art. The result is a software architecture proposal with configurations in the drone and off-grid stations that contemplate data collection from the IoT off-grid environment. The results are also presented with different selection algorithms used in machine learning and final execution in the prototype.

Associations of sensory and motor function with blood-based biomarkers of neurodegeneration and Alzheimer's disease in midlife.

Pathological biomarkers of dementia and Alzheimer's disease (AD) change decades before clinical symptoms. Common sensory and motor changes in aging adults may be early markers of neurodegeneration. We investigated if midlife sensory and motor functions in Beaver Dam Offspring Study (BOSS) participants (N = 1529) were associated with longitudinal changes in blood-based biomarkers of neurodegeneration (neurofilament light chain (NfL); total tau (TTau)) and AD (amyloid beta (Aß)). Mixed-effects models with baseline sensory and motor function as determinants and 10-year biomarker change as outcome were used. Participants with hearing impairment and worse motor function (among women) showed faster increases in NfL level over time (0.8% per year; 0.3% per year, respectively). There were no significant associations with TTau or Aß. We found consistent relationships between worse baseline hearing and motor function with a faster increase in neurodegeneration, specifically serum NfL level. Future studies with longer follow-up should determine if sensory and motor changes are more reflective of general neurodegeneration than AD-specific pathology and whether sensory and motor tests may be useful screening tools for neurodegeneration risk.

Impact of Fruit and Vegetable Protein vs. Milk Protein on Metabolic Control of Children with Phenylketonuria: A Randomized Crossover Controlled Trial.

Fruits and vegetables containing phenylalanine ≤ 75 mg/100 g (except potatoes) have little impact on blood phenylalanine in phenylketonuria (PKU). In a randomized, controlled, crossover intervention trial, we examined the effect of increasing phenylalanine intake from fruits and vegetables, containing phenylalanine 76−100 mg /100 g, compared with milk protein sources on blood phenylalanine control. This was a five-phase study (4 weeks each phase). In Phase A, patients remained on their usual diet and then were randomly allocated to start Phase B and C (an additional phenylalanine intake of 50 mg/day, then 100 mg from fruits and vegetables containing phenylalanine 76−100 mg/100 g) or Phase D and E (an additional phenylalanine intake of 50 mg/day then 100 mg/day from milk sources). There was a 7-day washout with the usual phenylalanine-restricted diet between Phase B/C and D/E. Blood phenylalanine was measured on the last 3 days of each week. If four out of six consecutive blood phenylalanine levels were >360 µmol/L in one arm, this intervention was stopped. Sixteen patients (median age 10.5 y; range 6−12 y) were recruited. At baseline, a median of 6 g/day (range: 3−25) natural protein and 60 g/day (range: 60−80) protein equivalent from protein substitute were prescribed. Median phenylalanine levels were: Phase A­240 µmol/L; Phase B­260 µmol/L; Phase C­280 µmol/L; Phase D­270 µmol/L and Phase E­280 µmol/L. All patients tolerated an extra 50 mg/day of phenylalanine from fruit and vegetables, containing phenylalanine 76−100 mg/100 g, but only 11/16 (69%) tolerated an additional 100 mg /day. With milk protein, only 8/16 (50%) tolerated an extra 50 mg/day and only 5/16 (31%) tolerated an additional 100 mg/day of phenylalanine. Tolerance was defined as maintaining consistent blood phenylalanine levels < 360 µmol/L throughout each study arm. There was a trend that vegetable protein had less impact on blood phenylalanine control than milk protein, but overall, the differences were not statistically significant (p = 0.152). This evidence supports the PKU European Guidelines cutoff that fruit and vegetables containing 76−100 mg phenylalanine/100 g should be calculated as part of the phenylalanine exchange system. Tolerance of the 'free use' of these fruits and vegetables depends on inter-patient variability but cannot be recommended for all patients with PKU.

Transitioning of protein substitutes in patients with phenylketonuria: evaluation of current practice.

BACKGROUND: In children with phenylketonuria (PKU), transitioning protein substitutes at the appropriate developmental age is essential to help with their long-term acceptance and ease of administration. We assessed the parental experiences in transitioning from a second stage to third stage liquid or powdered protein substitute in patients with PKU. RESULTS: Sixteen interviews (23 open-ended questions) were carried out with parents/caregivers of children with PKU (8 females, 50%) with a median age of 8 years (range 5-11 years), continuously treated with diet, and on a third stage protein substitute. Parents/caregivers identified common facilitators and barriers during the third stage protein substitute transition process. The main facilitators were: child and parent motivation, parent knowledge of the transition process, a role model with PKU, low volume and easy preparation of the third stage protein substitute (liquid/powder), anticipation of increasing child independence, lower parent workload, attractive packaging, better taste and smell, school and teacher support, dietetic plans and guidance, PKU social events, child educational materials and written resources. The main barriers were child aversion to new protein substitutes, poor child behaviour, child aged > 5 years, parental fear of change, the necessity for  parental time and persistence, loss of parental control, high product volume, different taste, smell, and texture of new protein substitutes, and peer bullying. CONCLUSION: A stepwise, supportive approach is necessary when transitioning from second to third stage protein substitutes in PKU. Future studies are needed to develop guidance to assist parents/caregivers, health professionals, and teachers during the transition process.

Altered gut microbiome diversity and function in patients with propionic acidemia.

Propionic acidemia (PA) is an inherited metabolic disorder of propionate metabolism, where the gut microbiota may play a role in pathophysiology and therefore, represent a relevant therapeutic target. Little is known about the gut microbiota composition and activity in patients with PA. Although clinical practice varies between metabolic treatment centers, management of PA requires combined dietary and pharmaceutical treatments, both known to affect the gut microbiota. This study aimed to characterize the gut microbiota and its metabolites in fecal samples of patients with PA compared with healthy controls from the same household. Eight patients (aged 3-14y) and 8 controls (4-31y) were recruited from Center 1 (UK) and 7 patients (11-33y) and 6 controls (15-54y) from Center 2 (Austria). Stool samples were collected 4 times over 3 months, alongside data on dietary intakes and medication usage. Several microbial taxa differed between patients with PA and controls, particularly for Center 1, e.g., Proteobacteria levels were increased, whereas butyrate-producing genera, such as Roseburia and Faecalibacterium, were decreased. Most measured microbial metabolites were lower in patients with PA, and butyrate was particularly depleted in patients from Center 1. Furthermore, microbiota profile of these patients showed the lowest compositional and functional diversity, and lowest stability over 3 months. As the first study to map the gut microbiota of patients with PA, this work represents an important step forward for developing new therapeutic strategies to further improve PA clinical status. New dietary strategies should consider microbial propionate production as well as butyrate production and microbiota stability.

Development of an Efficiency Platform Based on MQTT for UAV Controlling and DoS Attack Detection.

Several market sectors are attracted by the potential of unmanned aerial vehicles (UAVs), such as delivery, agriculture, and cinema, among others. UAVs are becoming part of Internet of Things (IoT) networks in the development of autonomous and scalable solutions. However, these vehicles are gradually becoming attractive targets for cyberattacks. This study proposes the development of an efficient platform based on the Message Queuing Telemetry Transport (MQTT) protocol for UAV control and Denial-of-Service (DoS) detection embedded in the UAV system. For the efficiency test, latency, network and memory consumption on the platform were measured, in addition to the correlation between payload and delay time. The results of efficiency tests were collected for the three levels of quality of service (QoS). A strong correlation greater than 90% was found between delay and data size for all QoS levels, showing almost a linear proportion. In DoS detection, the best results were a true positive rate (TPR) of 0.97 with 16 features from the AWID2 dataset using LightGBM with Bayesian optimization and data balancing. Unlike other studies, the built platform shows efficiency for UAV control and guarantees security in the communication with the broker and in the Wi-Fi UAV network.