A comparison of peak cough flow and peak expiratory flow in children with neuromuscular disorders.

Spirometry and peak cough flow testing (PCF) are commonly used in the respiratory assessment of children with a neuromuscular disorder (NMD). Testing uses two different machines, increases laboratory time, costs and resource utilisation. No studies have assessed the correlation between peak expiratory flow (PEF) obtained from spirometry and PCF in children with NMD using one device. An audit of children with a NMD managed at the Children's Hospital at Westmead in 2022-2024 aged < 20 years who performed spirometry and PCF testing on the same device (Vyaire Body BoxTM, Ultrasonic flow meter-based, or Vyaire PneumotachographTM, Pneumotach flow meter-based; Germany) was conducted to assess the correlation between PCF and PEF. Fifty-one sets of testing were identified, and 40 subjects (9F) had reproducible testing and were included. Median (range) age was 14.95 (7.20-19.00) years. Median PEF (L/min) was 4.05 (1.22-10.26) and median PCF (L/min) was 4.29 (1.69-10.82). PEF and PCF had a strong Pearson's correlation coefficient, (R = 0.97, p = 0.03). The coefficient of determination was 0.93. If laboratory resources permit, spirometry should be the test of choice for children with NMD. On average, spirometry required multiple practices to achieve reproducibility to meet ATS/ERS standards. PCF testing can be utilised for children where performing technically acceptable spirometry is not possible.

Can postural changes in spirometry in children with Duchenne muscular dystrophy predict sleep hypoventilation?

AIM: To explore the relationship between postural changes in lung function and polysomnography (PSG) in children with Duchenne muscular dystrophy (DMD). METHODS: In this prospective cross-sectional study, children with DMD performed spirometry in sitting and supine positions. A control group of age and gender matched healthy children also underwent postural lung function testing. PSG was performed within six months of spirometry. RESULTS: Seventeen children with DMD, aged 12.3 ± 3 years performed sitting spirometry. 14 (84%) performed acceptable spirometry in the supine position. Mean FEV1sit and FVCsit were 77% (SD ± 22) and 74% (SD ± 20.4) respectively, with mean% ΔFVC(sit-sup) 9% (SD ± 11) (range 2% to 20%), and was significantly greater than healthy controls 4% (n = 30, SD ± 3, P < 0.001). PSG data on the 14 DMD children with acceptable supine spirometry showed total AHI 6.9 ± 5.9/hour (0.3 to 29), obstructive AHI 5.2 ± 4.0/hour (0.2 to 10), and REM AHI 14.1 ± -5.3/hour (0.1 to 34.7). ΔFVC(sit-sup) had poor correlation with hypoventilation on polysomnography. CONCLUSION: Children with DMD and mild restrictive lung disease showed greater postural changes in spirometry than healthy controls but lower supine spirometry was not predictive of sleep hypoventilation.

Automated Dispensing Cabinet Overrides-An Evaluation of Necessity in a Pediatric Emergency Department.

OBJECTIVE: Automated dispensing cabinets, or ADCs, are often used at health care facilities to aid in the medication-use process. Although ADCs minimize certain medication errors, they introduce a new type of error involving overrides. Although helpful when used appropriately in emergencies, overrides bypass pharmacist verification and increase potential for patient harm through drug-drug interactions, medication allergies, inappropriate dosing, and more. The purpose of this study was to evaluate automated dispensing cabinets override pulls in a pediatric hospital's emergency department. The authors sought to discover whether overridden medications were being administered before verification (indicating it was needed emergently, thus justifying override) or after verification (indicating the override did not result in quicker administration and/or the medication was not emergent). METHODS: This was a retrospective, observational study. Data were collected from electronic health record reports from a 343-bed pediatric hospital's emergency department from October 13, 2019, to December 22, 2019. RESULTS: A total of 445 override pulls were identified during this time, and after data analysis, 99 override pulls remained in the data set. Overall, time from input of prescription into the electronic medical record to medication override was approximately 4 minutes. Pharmacist verification also took a median of four minutes after prescription input. However, administration took twice as long, at 8 minutes. On average, pharmacist verification occurred 4 minutes before medication administration. CONCLUSION: This research from a pediatric emergency department suggests that most situations did not require an immediate administration, and perhaps an override was unnecessary and could have been avoided.

Orbital-specific mapping of the ligand exchange dynamics of Fe(CO)5 in solution.

Transition-metal complexes have long attracted interest for fundamental chemical reactivity studies and possible use in solar energy conversion. Electronic excitation, ligand loss from the metal centre, or a combination of both, creates changes in charge and spin density at the metal site that need to be controlled to optimize complexes for photocatalytic hydrogen production and selective carbon-hydrogen bond activation. An understanding at the molecular level of how transition-metal complexes catalyse reactions, and in particular of the role of the short-lived and reactive intermediate states involved, will be critical for such optimization. However, suitable methods for detailed characterization of electronic excited states have been lacking. Here we show, with the use of X-ray laser-based femtosecond-resolution spectroscopy and advanced quantum chemical theory to probe the reaction dynamics of the benchmark transition-metal complex Fe(CO)5 in solution, that the photo-induced removal of CO generates the 16-electron Fe(CO)4 species, a homogeneous catalyst with an electron deficiency at the Fe centre, in a hitherto unreported excited singlet state that either converts to the triplet ground state or combines with a CO or solvent molecule to regenerate a penta-coordinated Fe species on a sub-picosecond timescale. This finding, which resolves the debate about the relative importance of different spin channels in the photochemistry of Fe(CO)5 (refs 4, 16 - 20), was made possible by the ability of femtosecond X-ray spectroscopy to probe frontier-orbital interactions with atom specificity. We expect the method to be broadly applicable in the chemical sciences, and to complement approaches that probe structural dynamics in ultrafast processes.

Evaluation of oncogenic cysteinyl leukotriene receptor 2 as a therapeutic target for uveal melanoma.

Uveal melanoma is a rare, but deadly, form of eye cancer that arises from melanocytes within the uveal tract. Although advances have emerged in treatment of the primary tumour, patients are still faced with vision loss, eye enucleation and lethal metastatic spread of the disease. Approximately 50% of uveal melanoma patients develop metastases, which occur most frequently in the liver. Metastatic patients encounter an extremely poor prognosis; as few as 8% survive beyond 2 years. Understanding of the genetic underpinnings of this fatal disease evolved in recent years with the identification of new oncogenic mutations that drive uveal melanoma pathogenesis. Despite this progress, the lack of successful therapies or a proven standard-of-care for uveal melanoma highlights the need for new targeted therapies. This review focuses on the recently identified CYSLTR2 oncogenic mutation in uveal melanoma. Here, we evaluate the current status of uveal melanoma and investigate how to better understand the role of this CYSLTR2 mutation in the disease and implications for patients harbouring this mutation.

Nutrition interventions for healthy ageing across the lifespan: a conference report.

Thanks to advances in modern medicine over the past century, the world's population has experienced a marked increase in longevity. However, disparities exist that lead to groups with both shorter lifespan and significantly diminished health, especially in the aged. Unequal access to proper nutrition, healthcare services, and information to make informed health and nutrition decisions all contribute to these concerns. This in turn has hastened the ageing process in some and adversely affected others' ability to age healthfully. Many in developing as well as developed societies are plagued with the dichotomy of simultaneous calorie excess and nutrient inadequacy. This has resulted in mental and physical deterioration, increased non-communicable disease rates, lost productivity and quality of life, and increased medical costs. While adequate nutrition is fundamental to good health, it remains unclear what impact various dietary interventions may have on improving healthspan and quality of life with age. With a rapidly ageing global population, there is an urgent need for innovative approaches to health promotion as individual's age. Successful research, education, and interventions should include the development of both qualitative and quantitative biomarkers and other tools which can measure improvements in physiological integrity throughout life. Data-driven health policy shifts should be aimed at reducing the socio-economic inequalities that lead to premature ageing. A framework for progress has been proposed and published by the World Health Organization in its Global Strategy and Action Plan on Ageing and Health. This symposium focused on the impact of nutrition on this framework, stressing the need to better understand an individual's balance of intrinsic capacity and functional abilities at various life stages, and the impact this balance has on their mental and physical health in the environments they inhabit.

Snapshots of the fluctuating hydrogen bond network in liquid water on the sub-femtosecond timescale with vibrational resonant inelastic x-ray scattering.

Liquid water molecules interact strongly with each other, forming a fluctuating hydrogen bond network and thereby giving rise to the anomalous phase diagram of liquid water. Consequently, symmetric and asymmetric water molecules have been found in the picosecond time average with IR and optical Raman spectroscopy. With subnatural linewidth resonant inelastic x-ray scattering (RIXS) at vibrational resolution, we take sub-femtosecond snapshots of the electronic and structural properties of water molecules in the hydrogen bond network. We derive a strong dominance of nonsymmetric molecules in liquid water in contrast to the gas phase on the sub-femtosecond timescale of RIXS and determine the fraction of highly asymmetrically distorted molecules.

Rydberg-resolved resonant inelastic soft x-ray scattering: dynamics at core ionization thresholds.

Resonant inelastic x-ray scattering spectra excited in the immediate vicinity of the core-level ionization thresholds of N2 have been recorded. Final states of well-resolved symmetry-selected Rydberg series converging to valence-level ionization thresholds with vibrational excitations are observed. The results are well described by a quasi-two-step model which assumes that the excited electron is unaffected by the radiative decay. This threshold dynamics simplifies the interpretation of resonant inelastic x-ray scattering spectra considerably and facilitates characterization of low-energy excited final states in molecular systems.

Geographical information software and shopper card data, aided in the discovery of a Salmonella Enteritidis outbreak associated with Turkish pine nuts.

In 2011, from August to November, the Monroe County Department of Public Health (MCDPH) investigated 47 salmonellosis cases. Geographical information software (GIS) was used to map the address locations of these cases. The resulting GIS analysis and culture information indicated that there were two distinct clusters of Salmonella that were geographically different. Pulsed-field gel electrophoresis (PFGE) testing was run at the New York State Department of Health Wadsworth Laboratory and identified S. Enteritidis (23 cases) and S. Typhimurium (10 cases). The epidemiological investigation identified Turkish pine nuts as the link between ill S. Enteritidis cases. Pine nut samples sent for laboratory testing were a PFGE match to human isolates with S. Enteritidis. A national recall of Turkish pine nuts ensued. A multistate outbreak was identified as a result of the initial investigation of MCDPH, in which 43 people were infected with the outbreak strain from five states. GIS software and shopper card data provided important tools in the epidemiological investigation.

Smolting in coastal cutthroat trout Onchorhynchus clarkii clarkii.

Gill Na(+) , K(+) -ATPase activity, condition factor and seawater (SW) challenges were used to assess the development of smolt characteristics in a cohort of hatchery coastal cutthroat trout Oncorhynchus clarkii clarkii from the Cowlitz River in Washington State, U.S.A. Gill Na(+) , K(+) -ATPase activity increased slightly in the spring, coinciding with an increase in hypo-osmoregulatory ability. These changes were of lesser magnitude than are observed in other salmonine species. Even at the peak of tolerance, these fish exhibited notable osmotic perturbations in full strength SW. Condition factor in these hatchery fish declined steadily through the spring. Wild captured migrants from four tributaries of the Columbia River had moderately elevated gill Na(+) , K(+) -ATPase activity, consistent with smolt development and with greater enzyme activity than autumn captured juveniles from one of the tributaries, Abernathy Creek. Migrant fish also had reduced condition factor. General linear models of 7 years of data from Abernathy Creek suggest that yearly variation, advancing photoperiod (as ordinal date) and fish size (fork length) were significant factors for predicting gill Na(+) , K(+) -ATPase activity in these wild fish. Both yearly variation and temperature were significant factors for predicting condition factor. These results suggest that coastal O. c. clarkii exhibit weakly developed characteristics of smolting. These changes are influenced by environmental conditions with great individual variation. The data suggest great physiological plasticity consistent with the variable life-history tactics observed in this species.

Using otolith chemical and structural analysis to investigate reservoir habitat use by juvenile Chinook salmon Oncorhynchus tshawytscha.

Isotopic composition of (87) Sr:(86) Sr and natural elemental tracers (Sr, Ba, Mg, Mn and Ca) were quantified from otoliths in juvenile and adult Chinook salmon Oncorhynchus tshawytscha to assess the ability of otolith microchemistry and microstructure to reconstruct juvenile O. tshawytscha rearing habitat and growth. Daily increments were measured to assess relative growth between natal rearing habitats. Otolith microchemistry was able to resolve juvenile habitat use between reservoir and natal tributary rearing habitats (within headwater basins), but not among catchments. Results suggest that 90% (n = 18) of sampled non-hatchery adults returning to the Middle Fork Willamette River were reared in a reservoir and 10% (n = 2) in natal tributary habitat upstream from the reservoir. Juveniles collected in reservoirs had higher growth rates than juveniles reared in natal streams. The results demonstrate the utility of otolith microchemistry and microstructure to distinguish among rearing habitats, including habitats in highly altered systems.

Analysis of image formation in optical palpation.

Optical palpation is an emerging elastography technique that generates two-dimensional images of mechanical stress at the tissue surface, with clinical applications such as intraoperative cancer detection and scar assessment. It has been implemented using various imaging systems, however, an analysis of how deformation of the sample and layer influences image formation has not been performed. Here, an analysis framework is presented, which assesses performance independently of the imaging system used. Optical palpation of varying samples and layers is simulated using finite element analysis and validated with experiments on silicone phantoms, providing a characterization of detectability, feature resolution, and contrast ratio. Using our framework, we demonstrate that computational optical palpation, which incorporates realistic assumptions of layer deformation, improves the feature resolution up to a factor of four. This framework can guide the development of optical palpation and aid in the selection of appropriate imaging system and layer properties for a given application.

Testing the amount of nicotinamide mononucleotide and urolithin A as compared to the label claim.

Healthy Longevity Medicine aims to optimize health by targeting aging processes across the lifespan. Addressing accelerated aging involves adaptation of lifestyle and the use of geroprotective drugs and supplements, including nutritional supplements and bioactive compounds. The Food and Drug Administration, under the Dietary Supplement Health and Education Act, categorizes bioactive compounds and medicinal products as dietary supplements. While numerous companies sell ingredients that can be deemed geroprotectors, there's limited oversight in their quality control. Governmental safety authorities only verify the presence of prohibited compounds, not the accuracy of ingredients listed on labels.Here, Nicotinamide mononucleotide and Urolithin A supplements, easily accessible online or in pharmacies, were tested for their active ingredient content. Results showed a significant deviation from the labeled amounts, ranging from + 28.6% to -100%. This indicates a considerable disparity in the quality of geroprotective supplements.To address this variability, collaboration between and within societies representing healthcare professionals, industry and regulatory bodies is imperative to ensure the quality of geroprotective supplements.

Quality, supply chain, and use of Trypanocidal drugs among camel keepers in north-eastern Kenya: A cross-sectional study.

The non-cyclic trypanosomiasis (surra), caused by Trypanosoma evansi, and mechanically transmitted by biting flies, hinders camel productivity in Kenya. Trypanocides are the most commonly used drugs to control surra. However, emergence of drug resistance by the parasites is a major limitation to control efforts. There is limited information on the quality of trypanocides, the supply chain and drug-use practices among camel keepers potentially contributing to development of drug resistance in Kenya. We sought to fill this gap by conducting a cross-sectional study among camel keepers in Isiolo and Marsabit counties, Kenya. We mapped the trypanocide drugs supply chain through quantitative and qualitative surveys. We administered a semi-structured questionnaire to camel keepers to generate data on trypanocides-use practices, including the types, sources, person who administers treatment, reconstitution, dosage, route and frequency of administration, among others. Additionally, we tested the quality of trypanocidal drugs retailed in the region. We mapped a total of 55 and 49 agro-veterinary outlets and general (ordinary) shops retailing veterinary drugs in the two counties, respectively. These comprised of 29 and 26 agro-veterinary outlets, as well as 24 and 25 general shops in Isiolo and Marsabit counties, respectively. Overall, the respondents experienced 283 surra cases in the three-month recall period, which were treated with trypanocides. The majority of these cases were diagnosed by camel owners (71.7%) and herders (24.1%). A significant proportion of the cases were treated by camel owners (54.8%), herders (35.3%), the owner's son (3.2%) and veterinary personnel (1.1%) (χ2 = 24.99, p = 0.000). Most of the households sourced the drugs from agro-veterinary outlets (59.0%), followed by general shops (19.8%), veterinary personnel (2.1%), and open-air markets (0.4%) (χ2 = 319.24, p = 0.000). Quinapyramine was the most (56.9%) predominantly used trypanocide in treatment of surra, followed by homidium (19.8%), isometamidium (15.9%), diminazene aceturate (6.7%), and ethidium (0.7%) (χ2 = 340.75, p < 0.000). Only a meager proportion of respondents (15.2%) used the drugs correctly as instructed by the manufacturers. We recorded an association between correct drug usage, with the person who administers the treatment (χ2 = 17.7, p = 0.003), and the type of trypanocide used (χ2 = 19.4, p < 0.001). All the drug samples tested had correct concentrations of active ingredient (100.0%), and therefore of good quality. We have demonstrated that whereas the trypanocides retailed in the region by authorized vendors are of good quality, there is widespread incorrect handling and use of the drugs by unqualified individuals, which may contribute to treatment failure and emergence of trypanocide resistance.

Interference between resonant and nonresonant inelastic x-ray scattering.

A detailed study of inelastic x-ray scattering from the ground state to the 3Σg(3σ(g)(-1)3s(g)1) state of the O2 molecule is presented. The observed angular anisotropy shows that the vibrational excitations within this final state are strongly dependent on the polarization of the incident radiation. The analysis demonstrates that this is a manifestation of interference between resonant and direct nonresonant inelastic x-ray scattering. This interference provides a new tool to monitor nuclear dynamics by relative rotation of the polarization vectors of the incident and scattered photons.

X-ray microdiffraction, TEM characterization and texture analysis of human dentin and enamel.

Human tooth is a complex bioceramic composite, which consists of enamel, dentin and the interface, the dentin-enamel junction (DEJ). The crystal properties and ultrastructure of the inorganic phase through the thickness of healthy human molar teeth were investigated using X-ray microdiffraction (µXRD), electron diffraction and transmission electron microscopy (TEM) techniques. The XRD data were analysed using the Le Bail profile fitting approach. The size and the texture of the crystallites forming enamel and dentin in the crown part of teeth were measured using both techniques and then compared. Results showed that the thickness of dentin crystallites was found to decrease towards the DEJ, whereas the thickness of the enamel crystallites increased from the DEJ towards the outer layers. It was demonstrated that enamel exhibited an increase of texture in 002 lattice planes from the DEJ towards the outer layers. Texture was also detected in 102 lattice planes. The texture effect in 002 planes at the scale of less than 1 µm was also demonstrated in dentin. The variation of lattice parameters as a function of the position within the thickness of dentin and enamel was also observed. The values of the nonuniform microstrain in the dentin and enamel crystallites were from 1.40 × 10(-6) % to 4.44 × 10(-5) %. The good correlation between XRD and TEM indicated that µXRD is a useful technique to study crystallography and microstructure of heterogeneous enamel and dentin. The observed gradient characteristics of texture and crystallite size in enamel and dentin maybe an evolutionary outcome to resist wear and fracture, thereby contributing to the excellent mechanical properties of teeth.

Mutation of the gene encoding cellular retinaldehyde-binding protein in autosomal recessive retinitis pigmentosa.

Inadequate levels of all-trans-retinol in the blood cause retinal dysfunction; hence, genes implicated in retinal vitamin-A metabolism represent candidates for inherited retinal degenerations. In the current study, molecular genetic analysis of a consanguineous pedigree segregating for non-syndromic autosomal recessive retinitis pigmentosa (arRP) indicated that the affected siblings were homozygous by descent for a G4763A nucleotide substitution in RLBP1, the gene encoding cellular retinaldehyde-binding protein (CRALBP). This substitution is predicted to replace an arginine with glutamine at residue 150. CRALBP is not expressed in photoreceptors but is abundant in the retinal pigment epithelium (RPE) and Müller cells of the neuroretina, where it carries 11-cis-retinol and 11-cis-retinaldehyde. When expressed in bacteria, recombinant CRALBP (rCRALBP) containing the R150Q substitution was less soluble than wild-type rCRALBP. Mutant rCRALBP was purified from the soluble cell lysate and the protein structure was verified by mass spectrometry. The mutant protein lacked the ability to bind 11-cis-retinaldehyde. These findings suggest that arRP in the current pedigree results from a lack of functional CRALBP, presumably leading to disruption of retinal vitamin-A metabolism.

COPD exacerbations -- a comparison of Irish data with European data from the ERS COPD Audit.

The European Respiratory Society COPD audit was a cross-sectional, multicentre study that analysed outcomes for COPD patients admitted to hospital with an exacerbation across Europe. We present the data on patients admitted to 11 Irish hospitals that participated in the audit. Among 237 patients (123 Male), the median age was 71 years and 79 (33%) patients were current smokers. 82 (35%) patients received high-flow oxygen before admission and 43 (18%) were cared for in a dedicated respiratory ward. 54 (23%) patients required ventilatory support. Median length of stay was 7 days, 98 (41%) patients were readmitted and 211 (89%) patients were alive at the 90 day follow up point. Irish patients were more likely to receive high-flow oxygen before admission, less likely to be managed in a dedicated respiratory ward and had a higher likelihood of readmission or death within 90 days than the European average.

The intensity of QuantiFERON TB-gold response does not differentiate active from latent tuberculosis.

We analyzed positive QuantiFERON (QFT) assays, performed between July 2009 and April 2011 in the Mercy University Hospital, Cork, Ireland, which included, 94 patients with latent tuberculosis (LTBI) and 35 patients with active tuberculosis. There was no difference in the intensity of response between patients with LTBI and active tuberculosis (p = 0.1589). In patients with LTBI, there were no correlations between age (p = 0.353), sex (p = 0.476), smoking (p = 0.323), contact (p = 0.612), Mantoux response (p = 0.055), Irish nationality (p=0.768), previous BCG vaccination (p = 0.504), WCC (p = 0.187), lymphocyte count (p = 0.786), neutrophil count (p = 0.157) and the intensity of QFT response. Similarly in patients with active TB, there were no correlations between these variables and QFT response. The intensity of QFT response does not help to differentiate active from LTBI. The intensity of QFT response is not influenced by age, sex, smoking, remoteness of contact history, Mantoux response, nationality, CXR abnormalities, BCG vaccination and peripheral lymphocyte count.

Two fine-scale channels for encoding motion and stereopsis within the human magnocellular stream.

In humans and non-human primates (NHPs), motion and stereopsis are processed within fine-scale cortical sites, including V2 thick stripes and their extensions into areas V3 and V3A that are believed to be under the influence of magnocellular stream. However, in both species, the relative functional organization (overlapping vs. none overlapping) of these sites remains unclear. Using high-resolution functional MRI (fMRI), we found evidence for two minimally-overlapping channels within human extrastriate areas that contribute to processing motion and stereopsis. Across multiple experiments that included different stimuli (random dots, gratings, and natural scenes), the functional selectivity of these channels for motion vs. stereopsis remained consistent. Furthermore, an analysis of resting-state functional connectivity revealed stronger functional connectivity within the two channels rather than between them. This finding provides a new perspective toward the mesoscale organization of the magnocellular stream within the human extrastriate visual cortex, beyond our previous understanding based on animal models.