Diet therapy and metabolic control among Chilean adults with a neonatal diagnosis of Phenylketonuria

Abstract Phenylketonuria (PKU) is an autosomal recessive defect affecting the metabolic pathway of phenylalanine (Phe), causing hyperphenylalaninemia and neurotoxicity. Diagnosis must occur in the neonatal period and treatment should begin as early as possible. Evidence implies that treatment adherence declines as age advances. The aim was to describe the diet of a subgroup of Chilean adults with PKU currently in follow-up. Fifty-three subjects (49% women) followed up between January 2021 to April 2023 were considered. The concentration of Phe (PheC) in dried blood spots measured by fluorometry and 24-hour dietary recalls were analyzed. The median PheC of the sample was 438µmol/L (interquartile range(IQR):351-585µmol/L). A protein intake of 1.35±0.3 gr/Kg/d was observed of which 87% came from the protein substitute without Phe. Participants had a median Phe intake of 459mg/d (IQR:327-976) and 13.1g/d of fiber intake. Most participants, 51% and 92% reported consuming fruits and vegetables, respectively, and 32% consumed Low-Protein foods. Regarding micronutrients, all participants exceeded 90% adequacy according to recommendations. For vitamin-D and vitamin-B12, 100% is provided by the protein substitute. According to our results, it is mandatory to establish transition programs toward adulthood, to constantly maintain good metabolic control, and to adapt diet therapy to their new lifestyle.

The Lucy Thermal Emission Spectrometer (L'TES) Instrument.

The Lucy Thermal Emission Spectrometer (L'TES) will provide remote measurements of the thermophysical properties of the Trojan asteroids studied by the Lucy mission. L'TES is build-to-print hardware copy of the OTES instrument flown on OSIRIS-REx. It is a Fourier Transform spectrometer covering the spectral range 5.71-100 µm (1750-100 cm-1) with spectral sampling intervals of 8.64, 17.3, and 34.6 cm-1 and a 7.3-mrad field of view. The L'TES telescope is a 15.2-cm diameter Cassegrain telescope that feeds a flat-plate Michelson moving mirror mounted on a linear voice-coil motor assembly to a single uncooled deuterated l-alanine doped triglycine sulfate (DLATGS) pyroelectric detector. A significant firmware change from OTES is the ability to acquire interferograms of different length and spectral resolution with acquisition times of 0.5, 1, and 2 seconds. A single ∼0.851 µm laser diode is used in a metrology interferometer to provide precise moving mirror control and IR sampling at 772 Hz. The beamsplitter is a 38-mm diameter, 1-mm thick chemical vapor deposited diamond with an antireflection microstructure to minimize surface reflection. An internal calibration cone blackbody target, together with observations of space, provides radiometric calibration. The radiometric precision in a single spectrum is ≤2.2 × 10-8 W cm-2 sr-1 /cm-1 between 300 and 1350 cm-1. The absolute temperature error is <2 K for scene temperatures >75 K. The overall L'TES envelope size is 37.6 × 29.0 × 30.4 cm, and the mass is 6.47 kg. The power consumption is 12.6 W average. L'TES was developed by Arizona State University with AZ Space Technologies developing the electronics. L'TES was integrated, tested, and radiometrically calibrated on the Arizona State University campus in Tempe, AZ. Initial data from space have verified the instrument's radiometric and spatial performance.

Spacecraft sample collection and subsurface excavation of asteroid (101955) Bennu.

Carbonaceous asteroids, such as (101955) Bennu, preserve material from the early Solar System, including volatile compounds and organic molecules. We report spacecraft imaging and spectral data collected during and after retrieval of a sample from Bennu's surface. The sampling event mobilized rocks and dust into a debris plume, excavating a 9-meter-long elliptical crater. This exposed material is darker, spectrally redder, and more abundant in fine particulates than the original surface. The bulk density of the displaced subsurface material was 500 to 700 kilograms per cubic meter, which is about half that of the whole asteroid. Particulates that landed on instrument optics spectrally resemble aqueously altered carbonaceous meteorites. The spacecraft stored 250 ± 101 grams of material, which will be delivered to Earth in 2023.

Mid-infrared emissivity of partially dehydrated asteroid (162173) Ryugu shows strong signs of aqueous alteration.

The near-Earth asteroid (162173) Ryugu, the target of Hayabusa2 space mission, was observed via both orbiter and the lander instruments. The infrared radiometer on the MASCOT lander (MARA) is the only instrument providing spectrally resolved mid-infrared (MIR) data, which is crucial for establishing a link between the asteroid material and meteorites found on Earth. Earlier studies revealed that the single boulder investigated by the lander belongs to the most common type found on Ryugu. Here we show the spectral variation of Ryugu's emissivity using the complete set of in-situ MIR data and compare it to those of various carbonaceous chondritic meteorites, revealing similarities to the most aqueously altered ones, as well as to asteroid (101955) Bennu. The results show that Ryugu experienced strong aqueous alteration prior to any dehydration.

Just a bad flu? Tackling the "infodemic" in Ireland through a comparative analysis of hospitalised cases of COVID-19 and influenza.

OBJECTIVES: COVID-19 infection has been compared to seasonal influenza as an argument against non-pharmacological population-based infection control measures known as "lockdowns". Our study sought to compare disease severity measures for patients in Ireland hospitalised with COVID-19 against those hospitalised with seasonal influenza. STUDY DESIGN: This is a retrospective population-based cohort study. METHODS: COVID-19 hospital episodes and seasonal influenza hospital episodes were identified using relevant International Classification of Disease (ICD-10) codes from the Irish national hospitalisation dataset. The occurrences of key metrics of disease severity, length of stay, intensive care admission, ventilatory support, haemodialysis and in-hospital mortality were measured and compared between the two groups using odds ratios with 95% confidence intervals (CIs), stratified by age. RESULTS: Hospitalised COVID-19 episodes had a mean length of stay more than twice as long as hospitalised influenza episodes (17.7 days vs 8.3 days). The likelihood of all measures of disease severity was greater in COVID-19 episodes, and the odds of in-hospital mortality were five-fold higher in this group compared with seasonal influenza episodes (OR 5.07, 95% CI 4.29-5.99, P < 0.001). Greater likelihood of increased disease severity was observed for COVID-19 episodes in most age groups. CONCLUSIONS: COVID-19 is a more severe illness than seasonal influenza in hospitalised cohorts. It is imperative that public health professionals ensure that evidence-based advocacy is part of the response to COVID-19 to tackle a dangerous "infodemic" that can undermine public health control measures.

Spectral Characterization of Bennu Analogs Using PASCALE: A New Experimental Set-Up for Simulating the Near-Surface Conditions of Airless Bodies.

We describe the capabilities, radiometric stability, and calibration of a custom vacuum environment chamber capable of simulating the near-surface conditions of airless bodies. Here we demonstrate the collection of spectral measurements of a suite of fine particulate asteroid analogs made using the Planetary Analogue Surface Chamber for Asteroid and Lunar Environments (PASCALE) under conditions like those found on Earth and on airless bodies. The sample suite includes anhydrous and hydrated physical mixtures, and chondritic meteorites (CM, CI, CV, CR, and L5) previously characterized under Earth- and asteroid-like conditions. And for the first time, we measure the terrestrial and extra-terrestrial mineral end members used in the olivine- and phyllosilicate-dominated physical mixtures under the same conditions as the mixtures and meteorites allowing us better understand how minerals combine spectrally when mixed intimately. Our measurements highlight the sensitivity of thermal infrared emissivity spectra to small amounts of low albedo materials and the composition of the sample materials. As the albedo of the sample decreases, we observe smaller differences between Earth- and asteroid-like spectra, which results from a reduced thermal gradient in the upper hundreds of microns in the sample. These spectral measurements can be compared to thermal infrared emissivity spectra of asteroid (101955) Bennu's surface in regions where similarly fine particulate materials may be observed to infer surface compositions.

Update on Dietary Compliance, Nutritional Status, and Neuropsychological Functioning in the Chilean Phenylketonuria cohort

Abstract Since 1992, Chile has had a Newborn Screening Program for Phenylketonuria (PKU), which currently has an incidence of 1:18,916 newborns. The objective of the current study was to describe the 2020 follow up of the Chilean PKU cohort. The variables analyzed were: nutritional status, dietary compliance and neuropsychological functioning. We conducted a descriptive cross-sectional statistical analysis. The 271 subjects with PKU had an average age of diagnosis of 17±8 days and a phenylalanine (Phe) level of 1122±546 umol/L. Approximately 80% of protein requirement came from a protein substitute. For those <18 years of age, 80% had good dietary compliance with Phe level between 120-360 umol/L and those >18 years had a median of 522 umol/L (95%CI 468 - 636). Forty-four percent of the active PKU cohort had overweight/obesity. Eighty-five percent of the cohort >4 years of age had a normal intelligence quotient (IQ) (score 80-120). We observed a negative correlation (p <0.001; 95% CI: - 0.5, -0.2) between IQ score and Phe level. The Chilean protocol and protein substitute subsidy for life, together with the follow-up and continuous education carried out by the clinical team has encouraged compliance.

Non-classical crystallisation pathway directly observed for a pharmaceutical crystal via liquid phase electron microscopy.

Non-classical crystallisation (NCC) pathways are widely accepted, however there is conflicting evidence regarding the intermediate stages of crystallisation, how they manifest and further develop into crystals. Evidence from direct observations is especially lacking for small organic molecules, as distinguishing these low-electron dense entities from their similar liquid-phase surroundings presents signal-to-noise ratio and contrast challenges. Here, Liquid Phase Electron Microscopy (LPEM) captures the intermediate pre-crystalline stages of a small organic molecule, flufenamic acid (FFA), a common pharmaceutical. High temporospatial imaging of FFA in its native environment, an organic solvent, suggests that in this system a Pre-Nucleation Cluster (PNC) pathway is followed by features exhibiting two-step nucleation. This work adds to the growing body of evidence that suggests nucleation pathways are likely an amalgamation of multiple existing non-classical theories and highlights the need for the direct evidence presented by in situ techniques such as LPEM.

Asteroid (101955) Bennu's weak boulders and thermally anomalous equator.

Thermal inertia and surface roughness are proxies for the physical characteristics of planetary surfaces. Global maps of these two properties distinguish the boulder population on near-Earth asteroid (NEA) (101955) Bennu into two types that differ in strength, and both have lower thermal inertia than expected for boulders and meteorites. Neither has strongly temperature-dependent thermal properties. The weaker boulder type probably would not survive atmospheric entry and thus may not be represented in the meteorite collection. The maps also show a high-thermal inertia band at Bennu's equator, which might be explained by processes such as compaction or strength sorting during mass movement, but these explanations are not wholly consistent with other data. Our findings imply that other C-complex NEAs likely have boulders similar to those on Bennu rather than finer-particulate regoliths. A tentative correlation between albedo and thermal inertia of C-complex NEAs may be due to relative abundances of boulder types.

Heterogeneous mass distribution of the rubble-pile asteroid (101955) Bennu.

The gravity field of a small body provides insight into its internal mass distribution. We used two approaches to measure the gravity field of the rubble-pile asteroid (101955) Bennu: (i) tracking and modeling the spacecraft in orbit about the asteroid and (ii) tracking and modeling pebble-sized particles naturally ejected from Bennu's surface into sustained orbits. These approaches yield statistically consistent results up to degree and order 3, with the particle-based field being statistically significant up to degree and order 9. Comparisons with a constant-density shape model show that Bennu has a heterogeneous mass distribution. These deviations can be modeled with lower densities at Bennu's equatorial bulge and center. The lower-density equator is consistent with recent migration and redistribution of material. The lower-density center is consistent with a past period of rapid rotation, either from a previous Yarkovsky-O'Keefe-Radzievskii-Paddack cycle or arising during Bennu's accretion following the disruption of its parent body.

Bright carbonate veins on asteroid (101955) Bennu: Implications for aqueous alteration history.

The composition of asteroids and their connection to meteorites provide insight into geologic processes that occurred in the early Solar System. We present spectra of the Nightingale crater region on near-Earth asteroid Bennu with a distinct infrared absorption around 3.4 micrometers. Corresponding images of boulders show centimeters-thick, roughly meter-long bright veins. We interpret the veins as being composed of carbonates, similar to those found in aqueously altered carbonaceous chondrite meteorites. If the veins on Bennu are carbonates, fluid flow and hydrothermal deposition on Bennu's parent body would have occurred on kilometer scales for thousands to millions of years. This suggests large-scale, open-system hydrothermal alteration of carbonaceous asteroids in the early Solar System.

Variations in color and reflectance on the surface of asteroid (101955) Bennu.

Visible-wavelength color and reflectance provide information about the geologic history of planetary surfaces. Here we present multispectral images (0.44 to 0.89 micrometers) of near-Earth asteroid (101955) Bennu. The surface has variable colors overlain on a moderately blue global terrain. Two primary boulder types are distinguishable by their reflectance and texture. Space weathering of Bennu surface materials does not simply progress from red to blue (or vice versa). Instead, freshly exposed, redder surfaces initially brighten in the near-ultraviolet region (i.e., become bluer at shorter wavelengths), then brighten in the visible to near-infrared region, leading to Bennu's moderately blue average color. Craters indicate that the time scale of these color changes is ~105 years. We attribute the reflectance and color variation to a combination of primordial heterogeneity and varying exposure ages.

Meteoritic Evidence for a Ceres-sized Water-rich Carbonaceous Chondrite Parent Asteroid.

Carbonaceous chondrite meteorites record the earliest stages of Solar System geo-logical activities and provide insight into their parent bodies' histories. Some carbonaceous chondrites are volumetrically dominated by hydrated minerals, providing evidence for low temperature and pressure aqueous alteration1. Others are dominated by anhydrous minerals and textures that indicate high temperature metamorphism in the absence of aqueous fluids1. Evidence of hydrous metamorphism at intermediate pressures and temperatures in carbonaceous chondrite parent bodies has been virtually absent. Here we show that an ungrouped, aqueously altered carbonaceous chondrite fragment (numbered 202) from the Almahata Sitta (AhS) meteorite contains an assemblage of minerals, including amphibole, that reflect fluid-assisted metamorphism at intermediate temperatures and pressures on the parent asteroid. Amphiboles are rare in carbonaceous chondrites, having only been identified previously as a trace component in Allende (CV3oxA) chondrules2. Formation of these minerals requires prolonged metamorphism in a large (~640-1800 km diameter), unknown asteroid. Because Allende and AhS 202 represent different asteroidal parent bodies, intermediate conditions may have been more widespread in the early Solar System than recognized from known carbonaceous chondrite meteorites, which are likely a biased sampling.

Virtual arthroplasty follow-up: five-year data from a district general hospital.

INTRODUCTION: Follow-up after hip and knee arthroplasty is advocated to identify asymptomatic loosening and improve patient satisfaction. There are, however, financial and time implications associated with regular clinic appointments. Assessment through virtual means has been suggested as an alternative. MATERIALS AND METHODS: At the West Suffolk Hospital, following arthroplasty surgery of the lower limb, patients are followed-up via a questionnaire at one and five years postoperatively, then subsequently at five-yearly intervals. Patients are recalled based on the outcome of these assessments. Using a locally compiled data base we identified all patients reviewed between 2011 and 2015 using this virtual assessment process and examined their outcomes. RESULTS: During the five years of follow-up, 5,380 patients were eligible for assessment. Compliance varied from 77% follow up for hips and 83% for knees. Ten patients were recalled following total hip replacement, eight for x-ray changes and one for a poor satisfaction score. Five went on to undergo revision surgery. Some 56 recalls to clinic following knee arthroplasty were seen; 42 due to a poor Oxford Knee Score, 6 with associated x-ray abnormalities and 6 isolated abnormal x-rays. Five subsequently underwent revision surgery; 30 (54%) were discharged after initial review and 18 (32%) were referred to different subspecialties.As a result of the virtual review process, 4,219 clinic appointments were avoided, with no documented admissions as a result of a missed complication from virtual review. DISCUSSION: A virtual arthroplasty clinic significantly reduces the number of patients attending regular follow-up clinics, without compromising safe practice.

Evidence for widespread hydrated minerals on asteroid (101955) Bennu.

Early spectral data from the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission reveal evidence for abundant hydrated minerals on the surface of near-Earth asteroid (101955) Bennu in the form of a near-infrared absorption near 2.7 µm and thermal infrared spectral features that are most similar to those of aqueously altered CM carbonaceous chondrites. We observe these spectral features across the surface of Bennu, and there is no evidence of substantial rotational variability at the spatial scales of tens to hundreds of meters observed to date. In the visible and near-infrared (0.4 to 2.4 µm) Bennu's spectrum appears featureless and with a blue (negative) slope, confirming previous ground-based observations. Bennu may represent a class of objects that could have brought volatiles and organic chemistry to Earth.

The unexpected surface of asteroid (101955) Bennu.

NASA'S Origins, Spectral Interpretation, Resource Identification and Security-Regolith Explorer (OSIRIS-REx) spacecraft recently arrived at the near-Earth asteroid (101955) Bennu, a primitive body that represents the objects that may have brought prebiotic molecules and volatiles such as water to Earth1. Bennu is a low-albedo B-type asteroid2 that has been linked to organic-rich hydrated carbonaceous chondrites3. Such meteorites are altered by ejection from their parent body and contaminated by atmospheric entry and terrestrial microbes. Therefore, the primary mission objective is to return a sample of Bennu to Earth that is pristine-that is, not affected by these processes4. The OSIRIS-REx spacecraft carries a sophisticated suite of instruments to characterize Bennu's global properties, support the selection of a sampling site and document that site at a sub-centimetre scale5-11. Here we consider early OSIRIS-REx observations of Bennu to understand how the asteroid's properties compare to pre-encounter expectations and to assess the prospects for sample return. The bulk composition of Bennu appears to be hydrated and volatile-rich, as expected. However, in contrast to pre-encounter modelling of Bennu's thermal inertia12 and radar polarization ratios13-which indicated a generally smooth surface covered by centimetre-scale particles-resolved imaging reveals an unexpected surficial diversity. The albedo, texture, particle size and roughness are beyond the spacecraft design specifications. On the basis of our pre-encounter knowledge, we developed a sampling strategy to target 50-metre-diameter patches of loose regolith with grain sizes smaller than two centimetres4. We observe only a small number of apparently hazard-free regions, of the order of 5 to 20 metres in extent, the sampling of which poses a substantial challenge to mission success.

Characterization of Phenyalanine Hydroxylase Gene Mutations in Chilean PKU Patients.

Phenylketonuria (PKU, OMIM 261600) is an autosomal recessive disease, caused by mutations in the Phenylalanine Hydroxylase (PAH) gene situated in chromosome 12q22-q24.2. This gene has 13 exons. To date, 991 mutations have been described. The genotype is one of the main factors that determine the phenotype of this disease. OBJECTIVE: Characterize PKU genotype and phenotype seen in Chilean PKU patients. METHODS: We studied the PAH gene by restriction fragment length polymorphism (RFLP) and/or sequencing techniques to identify pathogenic mutations in 71 PKU subjects. We classified the phenotype according to Guldberg predicted value. RESULTS: We identified 26 different mutations in 134 of the 142 alleles studied (94.4%), 88.7% of the subjects had biallelic pathogenic mutations while 11.3% had only one pathogenic mutation identified. Compound heterozygous represented 85.9% of the cases. Exon 7 included the majority of mutations (26.9%) and 50% of mutations were missense. The most frequent mutations were c.1066-11G > A, c.442-?_509+?del and p.Val388Met. The majority of subjects (52.3%) had the classic phenotype. CONCLUSIONS: The most frequent mutations in our Chilean PKU population were p.Val388Met, c.442?_509+?del and c.1066-11G > A. It is possible to predict phenotype by detecting the genotype, and use this information to determine disease prognosis and adjust patient's medical and nutritional management accordingly.

Chemistry, mineralogy, and grain properties at Namib and High dunes, Bagnold dune field, Gale crater, Mars: A synthesis of Curiosity rover observations.

The Mars Science Laboratory Curiosity rover performed coordinated measurements to examine the textures and compositions of aeolian sands in the active Bagnold dune field. The Bagnold sands are rounded to subrounded, very fine to medium sized (~45-500 µm) with ≥6 distinct grain colors. In contrast to sands examined by Curiosity in a dust-covered, inactive bedform called Rocknest and soils at other landing sites, Bagnold sands are darker, less red, better sorted, have fewer silt-sized or smaller grains, and show no evidence for cohesion. Nevertheless, Bagnold mineralogy and Rocknest mineralogy are similar with plagioclase, olivine, and pyroxenes in similar proportions comprising >90% of crystalline phases, along with a substantial amorphous component (35% ± 15%). Yet Bagnold and Rocknest bulk chemistry differ. Bagnold sands are Si enriched relative to other soils at Gale crater, and H2O, S, and Cl are lower relative to all previously measured Martian soils and most Gale crater rocks. Mg, Ni, Fe, and Mn are enriched in the coarse-sieved fraction of Bagnold sands, corroborated by visible/near-infrared spectra that suggest enrichment of olivine. Collectively, patterns in major element chemistry and volatile release data indicate two distinctive volatile reservoirs in Martian soils: (1) amorphous components in the sand-sized fraction (represented by Bagnold) that are Si-enriched, hydroxylated alteration products and/or H2O- or OH-bearing impact or volcanic glasses and (2) amorphous components in the fine fraction (<40 µm; represented by Rocknest and other bright soils) that are Fe, S, and Cl enriched with low Si and adsorbed and structural H2O.

Stimulation of Critically Ill Patients: Relationship to Sedation.

OBJECTIVES: To describe the number and type of stimulation events and the relationship of stimulation to sedation level in patients receiving mechanical ventilation. METHODS: A 4-hour direct observation was conducted in 103 patients receiving mechanical ventilation. Stimulation events and sedation level before and after the stimulation were documented. Eight categories of stimulation events were developed in a previous pilot study of 36 patients receiving mechanical ventilation. Sedation was measured continuously by using a processed electroencephalographic score (patient state index [PSI]) and intermittently by using the Richmond Agitation-Sedation Scale. RESULTS: Patients were mostly alert/mildly sedated (54.4%) at study enrollment. During the 349 hours of observation, 58.8% of the time included stimulation events. General auditory types of stimulation were most common (41.2% of observed time), followed by respiratory management and tactile family stimulation. For all events, auditory-talking, tactile-general, tactile-noxious, and tactile-highly noxious stimuli were associated with higher PSIs (all P < .001) after stimulation; other stimuli were not. Level of consciousness influenced response to stimuli, with almost all types of stimuli increasing PSI for patients more deeply sedated (PSI < 60) just before the stimuli. However, the effect of stimulation on PSI for more alert patients (PSI > 60) was small and variable. DISCUSSION: Critically ill patients receiving mechanical ventilation are subjected to various forms of auditory and tactile stimulation frequently throughout the day. All types of stimuli increased arousal in patients who were more deeply sedated. The effect of stimulation in patients who were not deeply sedated was minimal and inconsistent.

In situ radiometric and exposure age dating of the martian surface.

We determined radiogenic and cosmogenic noble gases in a mudstone on the floor of Gale Crater. A K-Ar age of 4.21 ± 0.35 billion years represents a mixture of detrital and authigenic components and confirms the expected antiquity of rocks comprising the crater rim. Cosmic-ray-produced (3)He, (21)Ne, and (36)Ar yield concordant surface exposure ages of 78 ± 30 million years. Surface exposure occurred mainly in the present geomorphic setting rather than during primary erosion and transport. Our observations are consistent with mudstone deposition shortly after the Gale impact or possibly in a later event of rapid erosion and deposition. The mudstone remained buried until recent exposure by wind-driven scarp retreat. Sedimentary rocks exposed by this mechanism may thus offer the best potential for organic biomarker preservation against destruction by cosmic radiation.