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BMC Nephrology Jun 2024Salt intake in CKD patients can affect cardiovascular risk and kidney disease progression. Twenty-four hour (24h) urine collections are often used to investigate salt...
BACKGROUND
Salt intake in CKD patients can affect cardiovascular risk and kidney disease progression. Twenty-four hour (24h) urine collections are often used to investigate salt metabolism but are cumbersome to perform. We assessed urinary sodium (U-Na) concentration in spot urine samples and investigated the correlation with 24h U-Na excretion and concentration in CKD patients under nephrological care. Further, we studied the role of CKD stage and diuretics and evaluated the performance of commonly used formulas for the prediction of 24h U-Na excretion from spot urine samples.
METHODS
One hundred eight patients of the German Chronic Kidney Disease (GCKD) study were included. Each participant collected a 24h urine and two spot urine samples within the same period. The first spot urine sample (AM) was part of the second morning urine. The second urine sample was collected before dinner (PM). Patients were advised to take their medication as usual without changing dietary habits. U-Na concentrations in the two spot urine samples and their average ((AM + PM)/2) were correlated with U-Na concentration and total Na excretion in the 24h urine collections. Correlations were subsequently studied after stratification by CKD stage and diuretic intake. The usefulness of three commonly applied equations to estimate 24h U-Na excretion from spot urine samples (Kawasaki, Tanaka and Intersalt) was determined using Bland-Altman plots, analyses of sensitivity, specificity, as well as positive (PPV) and negative predictive values (NPV).
RESULTS
Participants (42 women, 66 men) were on average (± SD) 62.2 (± 11.9) years old, with a mean serum creatinine of 1.6 (± 0.5) mg/dl. 95% had arterial hypertension, 37% diabetes mellitus and 55% were on diuretics. The best correlation with 24h U-Na total excretion was found for the PM spot U-Na sample. We also found strong correlations when comparing spot and 24h urine U-Na concentration. Correction of spot U-Na for U-creatinine did not improve strength of correlations. Neither CKD stage, nor intake of diuretics had significant impact on these correlations. All examined formulas revealed a significant mean bias. The lowest mean bias and the strongest correlation between estimated and measured U-Na excretion in 24h were obtained using the Tanaka-formula. Also, application of the Tanaka-formula with PM U-Na provided best sensitivity, specificity, PPV and NPV to estimate U-Na excretion > 4g/d corresponding to a salt consumption > 10g/d.
CONCLUSION
U-Na concentration of spot urine samples correlated with 24h U-Na excretion especially when PM spot U-Na was used. However, correlation coefficients were relatively low. Neither CKD stage nor intake of diuretics appeared to have an influence on these correlations. There was a significant bias for all tested formulas with the Tanaka-formula providing the strongest correlation with measured 24h U-Na excretion. In summary, using spot urine samples together with the Tanaka-formula in epidemiological studies appears feasible to determine associations between approximate salt intake and outcomes in CKD patients. However, the usefulness of spot-urine samples to guide and monitor salt consumption in individual patients remains limited.
Topics: Humans; Female; Male; Renal Insufficiency, Chronic; Middle Aged; Sodium; Aged; Urine Specimen Collection; Diuretics; Predictive Value of Tests; Urinalysis; Adult
PubMed: 38937680
DOI: 10.1186/s12882-024-03639-2 -
ENeuro Jun 2024Elevated intraocular pressure (IOP) triggers glaucoma by damaging the output neurons of the retina called retinal ganglion cells (RGCs). This leads to the loss of RGC...
Elevated intraocular pressure (IOP) triggers glaucoma by damaging the output neurons of the retina called retinal ganglion cells (RGCs). This leads to the loss of RGC signaling to visual centers of the brain such as the dorsolateral geniculate nucleus (dLGN), which is critical for processing and relaying information to the cortex for conscious vision. In response to altered levels of activity or synaptic input, neurons can homeostatically modulate postsynaptic neurotransmitter receptor numbers, allowing them to scale their synaptic responses to stabilize spike output. While prior work has indicated unaltered glutamate receptor properties in the glaucomatous dLGN, it is unknown whether glaucoma impacts dLGN inhibition. Here, using DBA/2J mice, which develop elevated IOP beginning at 6-7 months of age, we tested whether the strength of inhibitory synapses on dLGN thalamocortical relay neurons is altered in response to the disease state. We found an enhancement of feed-forward disynaptic inhibition arising from local interneurons along with increased amplitude of quantal inhibitory synaptic currents. A combination of immunofluorescence staining for the GABA-α1 receptor subunit, peak-scaled nonstationary fluctuation analysis, and measures of homeostatic synaptic scaling pointed to an approximately 1.4-fold increase in GABA receptors at post-synaptic inhibitory synapses, although several pieces of evidence indicate a non-uniform scaling across inhibitory synapses within individual relay neurons. Together, these results indicate an increase in inhibitory synaptic strength in the glaucomatous dLGN, potentially pointing toward homeostatic compensation for disruptions in network and neuronal function triggered by increased IOP. Elevated eye pressure in glaucoma leads to loss of retinal outputs to the dorsolateral geniculate nucleus (dLGN), which is critical for relaying information to the cortex for conscious vision. Alterations in neuronal activity, as could arise from excitatory synapse loss, can trigger homeostatic adaptations to synaptic function that attempt to maintain activity within a meaningful dynamic range, although whether this occurs uniformly at all synapses within a given neuron or is a non-uniform process is debated. Here, using a mouse model of glaucoma, we show that dLGN inhibitory synapses undergo non-uniform upregulation due to addition of post-synaptic GABA receptors. This is likely to be a neuronal adaptation to glaucomatous pathology in an important sub-cortical visual center.
PubMed: 38937109
DOI: 10.1523/ENEURO.0263-24.2024 -
The Journal of Pharmacology and... Jun 2024Through its pathological and genetic association to Parkinson's Disease (PD), α-synuclein (α-syn) remains a favorable therapeutic target that is being investigated...
Through its pathological and genetic association to Parkinson's Disease (PD), α-synuclein (α-syn) remains a favorable therapeutic target that is being investigated using various modalities, including many passive immunotherapy approaches clinically targeting different forms of α-syn and epitopes. Whereas published studies from some immunotherapy trials have demonstrated engagement in plasma, none have shown direct drug-antigen interactions in the disease-relevant compartment, the central nervous system (CNS). Cinpanemab (BIIB054) selectively targets pathological aggregated α-syn with low affinity binding to monomeric forms. The avidity-driven binding, low drug concentration, and the very low α-syn levels plus its heterogeneous nature in cerebrospinal fluid (CSF) made it not possible to measure drug-target interactions by conventional assays. Here we overcame these challenges by using zero-length crosslinking to stabilize the BIIB054-α-syn complexes and then quantified the crosslinked complexes using a Meso Scale Discovery (MSD) electrochemiluminescence assay. CSF samples from healthy volunteers (HV, n=46) and individuals with PD (PD, n=18) from study 228HV101 (Phase I clinical trial of BIIB054), demonstrated dose- and time- dependent binding of cinpanemab to α-syn with measurable complexes detected at doses {greater than or equal to}15 mg/kg. Complex formation displayed a direct positive correlation to drug concentration (Spearman rank correlation = 0.8295 (HV), 0.8032 (PD) p < 0.0001 (HV, PD)). The observed binding of cinpanemab to α-syn in CSF is consistent with its low intrinsic affinity for α-syn monomer and provides evidence that the drug is behaving with expected binding dynamics in the central nervous system compartment. A zero-length cross-linking method with MSD detection was developed to enable quantification of cinpanemab-α-syn complexes in Phase 1 clinical CSF samples by preventing signal loss caused by their rapid dissociation. Observed dose- and time-dependent binding were consistent with cinpanemab's affinity for α-syn and provided confidence that the drug had engaged its target at the desired site of action. This is the first demonstration of α-syn binding by an antibody in clinical samples from the CNS.
PubMed: 38936981
DOI: 10.1124/jpet.124.002199 -
The Kobe Journal of Medical Sciences Jun 2024The fitting of oxygen mask affects the performance of it such as oxygenation or CO₂ elimination. The intersurgical EcoLite™ adult high-concentration oxygen mask... (Observational Study)
Observational Study
Oxygenation and Carbon Dioxide Rebreathing of a Well-fitting Non-rebreathing EcoLite™ Mask with a Reservoir: A Single-center Prospective Observational Study in Healthy Volunteers.
BACKGROUND
The fitting of oxygen mask affects the performance of it such as oxygenation or CO₂ elimination. The intersurgical EcoLite™ adult high-concentration oxygen mask (EcoLite with a reservoir, Intersurgical, UK) was developed to give well-fitting. The purpose of this study is to evaluate the performance of EcoLite with a reservoir compared to the conventional mask.
METHODS
Ten healthy volunteers were included in this study. EcoLite with a reservoir and conventional mask were given to patients at different oxygen flow rates (5, 8, 10, 12, and 15 L/min). Fraction of inspiratory O₂ (FO₂) and partial pressure of inspiratory CO₂ (PCO₂) were measured by a sampling tube at the middle pharynx inserted via nose.
RESULTS
The EcoLite with a reservoir had a significantly higher FO₂ than the control reservoir mask. However, the PCO₂ was significantly higher in the EcoLite with a reservoir than in the control reservoir mask, especially when the oxygen flow rate was low.
CONCLUSION
The EcoLite with a reservoir provided improved oxygenation and a better fit than the conventional reservoir masks in healthy volunteers. However, the EcoLite with a reservoir might cause higher CO₂ rebreathing at low oxygen flow rates.
Topics: Humans; Carbon Dioxide; Male; Adult; Healthy Volunteers; Masks; Prospective Studies; Female; Oxygen; Young Adult
PubMed: 38936879
DOI: 10.24546/0100489920 -
Journal of Cardiovascular Magnetic... Jun 2024In-vivo diffusion tensor CMR (DT-CMR) is an emerging technique for microstructural tissue characterisation in the myocardium. Most studies are performed at 3T, where...
BACKGROUND
In-vivo diffusion tensor CMR (DT-CMR) is an emerging technique for microstructural tissue characterisation in the myocardium. Most studies are performed at 3T, where higher signal to noise ratio (SNR) should benefit this signal starved method. However, a few studies have suggested that DT-CMR is possible at 1.5T, where EPI artefacts may be less severe and 1.5T hardware is more widely available.
METHODS
We recruited 20 healthy volunteers and performed mid-ventricular short axis DT-CMR at 1.5 T and 3 T. Acquisitions were performed at peak systole and end-diastole using both stimulated echo acquisition mode (STEAM) and motion compensated spin-echo (MCSE) sequences at matched spatial resolutions. DT-CMR parameters were averaged over the LV and compared between 1.5 T and 3 T sequences using both datasets with and without the blow reference data included.
RESULTS
Eleven (1.5T) and 12 (3T) diastolic MCSE acquisitions were rejected as the helix angle (HA) demonstrated <50% normal appearance circumferentially or the acquisition was abandoned due to poor image quality; a maximum of one acquisition was rejected for other datasets. Subjective HA map quality was significantly better at 3T than 1.5T for STEAM (p<0.05), but not for MCSE and other DT-CMR quality measures were consistent with improvements in STEAM at 3T over 1.5T. When b data was excluded, no significant differences in mean diffusivity were observed between field strengths, but fractional anisotropy was significantly higher at 1.5T than 3T for STEAM systole (p<0.05). Absolute second eigenvector orientation (E2A, sheetlet angle) was significantly higher at 1.5T than 3T for MCSE systole and STEAM diastole, but significantly lower for STEAM systole (all p<0.05). Transmural HA distribution was less steep at 1.5T than 3T for STEAM diastole data (p<0.05). SNR in the b images was higher at 3T than 1.5T for all acquisitions (p<0.05).
CONCLUSION
While 3T provides benefits in terms of SNR, both STEAM and MCSE can be performed at 1.5T. However, MCSE is unreliable in diastole at both field strengths and STEAM benefits from the improved SNR at 3T over 1.5T. Future clinical research studies may be able to leverage the wider availability of 1.5T CMR hardware where MCSE acquisitions are desirable.
PubMed: 38936803
DOI: 10.1016/j.jocmr.2024.101052 -
Animal : An International Journal of... Jun 2024Feed efficiency is an important trait of dairy production. However, assessing feed efficiency is constrained by the associated cost and difficulty in measuring...
Feed efficiency is an important trait of dairy production. However, assessing feed efficiency is constrained by the associated cost and difficulty in measuring individual feed intake, especially on pastures. The objective of this study was to investigate short-term feed efficiency traits of herbage-fed dairy cows and screening of potential biomarkers (n = 238). Derived feed efficiency traits were ratio-based (i.e., feed conversion ratio (FCR) and N use efficiency (NUE)) or residual-based (i.e., residual feed intake (RFI), residual energy intake (REI), and residual N intake (RNI)). Thirty-eight Holstein and 16 Swiss Fleckvieh dairy cows underwent a 7-d measurement period during mid- and/or late-lactation. The experimental data (n = 100 measurement points) covered different lactational and herbage-fed system situations: mid-lactation grazing (n = 56), late-lactation grazing (n = 28), and late-lactation barn feeding (n = 16). During each measuring period, the individual herbage intake of each cow was estimated using the n-alkane marker technique. For each cow, biomarkers representing milk constituents (n = 109), animal characteristics (n = 13), behaviour, and activity (n = 46), breath emissions (n = 3), blood constituents (n = 35), surface, and rectal temperature (n = 29), hair cortisol (n = 1), and near-infrared (NIR) spectra of faeces and milk (n = 2) were obtained. The relationships between biomarkers and efficiency traits were statistically analysed with univariate linear regression and for NIR spectra using partial least squares regression with feed efficiency traits. The feed efficiency traits were interrelated with each other (r: -0.57 to -0.86 and 0.49-0.81). The biomarkers showed varying R values in explaining the variability of feed efficiency traits (FCR: 0.00-0.66, NUE: 0.00-0.74, RFI: 0.00-0.56, REI: 0.00-0.69, RNI: 0.00-0.89). Overall, the feed efficiency traits were best explained by NIR spectral characteristics of milk and faeces (R: 0.25-0.89). Biomarkers show potential for predicting feed efficiency in herbage-fed dairy cows. NIR spectra data analysis of milk and faeces presents a promising method for estimating individual feed efficiency upon further validation of prediction models. Future applications will depend on the ability to improve the robustness of biomarkers to predict feed efficiency in a greater variety of environments (locations), managing conditions, feeding systems, production intensities, and other aspects.
PubMed: 38935984
DOI: 10.1016/j.animal.2024.101211 -
Animal : An International Journal of... May 2024No single enteric CH mitigating strategy has been consistently effective or is readily applicable to ruminants in grassland systems. When CH mitigating strategies are...
No single enteric CH mitigating strategy has been consistently effective or is readily applicable to ruminants in grassland systems. When CH mitigating strategies are effective under grazing conditions, mitigation is mild to moderate at best. A study was conducted to evaluate the potential of combining two CH mitigation strategies deemed feasible to apply in grazing dairy cows, the methanogenesis inhibitor 3-nitrooxypropanol additive (3-NOP) and cottonseed supplementation (CTS), seeking to enhance their individual CH mitigating potential. Forty-eight dairy cows were evaluated in a continuous grazing study and supplemented with either a starch-based concentrate (STA) or one that contained cottonseeds (1.75 kg DM/d; CTS), and with either 19 g/d of 10% 3-NOP (Bovaer®) or the additive's carrier (placebo), in a 2 × 2 factorial arrangement of treatments. Treatments were supplied mixed with a concentrate supplement (5 kg/d as fed) and offered in two equal rations at milking. Methane emissions were measured on weeks 4 and 8 using the sulphur hexafluoride tracer gas technique over a 5-d period. The 3-NOP and CTS treatments tended to interact on absolute CH such that 3-NOP decreased CH by 13.4% with STA, but there was no mitigation with 3-NOP and CTS. Treatment interactions were also obtained for CH yield, where 3-NOP tended to decrease CH when supplied with STA, and tended to increase it with CTS. The increase in CH yield with the CTS diet was driven by a numerical decrease in DM intake. Methane intensity was not affected by the 3-NOP or CTS treatments. Total volatile fatty acids in ruminal fluid were not affected by 3-NOP supplementation, but a reduction in acetate and an increase in propionate proportion occurred, resulting in decreased acetate: propionate. The 3-NOP additive decreased grass intake; however, energy-corrected milk yield and milk composition were largely unaffected. Milk urea increased with 3-NOP supplementation. Combining twice daily supplementation of 3-NOP and CTS did not enhance their CH mitigation potential when fed to grazing dairy cows. The relatively low inhibition of CH production by 3-NOP compared to studies with total mixed rations may result from the mode of delivery (pulse dosed twice daily) and time gap caused by experimental handling and moving of animals to pasture after 3-NOP supplementation in the milking parlour, which could have impaired the synchrony between the additive presence in the rumen and grass intake in paddocks.
PubMed: 38935983
DOI: 10.1016/j.animal.2024.101203 -
JMIR Bioinformatics and Biotechnology Jun 2023There is a great need to develop a computational approach to analyze and exploit the information contained in gene expression data. The recent utilization of nonnegative...
Decision of the Optimal Rank of a Nonnegative Matrix Factorization Model for Gene Expression Data Sets Utilizing the Unit Invariant Knee Method: Development and Evaluation of the Elbow Method for Rank Selection.
BACKGROUND
There is a great need to develop a computational approach to analyze and exploit the information contained in gene expression data. The recent utilization of nonnegative matrix factorization (NMF) in computational biology has demonstrated the capability to derive essential details from a high amount of data in particular gene expression microarrays. A common problem in NMF is finding the proper number rank (r) of factors of the degraded demonstration, but no agreement exists on which technique is most appropriate to utilize for this purpose. Thus, various techniques have been suggested to select the optimal value of rank factorization (r).
OBJECTIVE
In this work, a new metric for rank selection is proposed based on the elbow method, which was methodically compared against the cophenetic metric.
METHODS
To decide the optimum number rank (r), this study focused on the unit invariant knee (UIK) method of the NMF on gene expression data sets. Since the UIK method requires an extremum distance estimator that is eventually employed for inflection and identification of a knee point, the proposed method finds the first inflection point of the curvature of the residual sum of squares of the proposed algorithms using the UIK method on gene expression data sets as a target matrix.
RESULTS
Computation was conducted for the UIK task using gene expression data of acute lymphoblastic leukemia and acute myeloid leukemia samples. Consequently, the distinct results of NMF were subjected to comparison on different algorithms. The proposed UIK method is easy to perform, fast, free of a priori rank value input, and does not require initial parameters that significantly influence the model's functionality.
CONCLUSIONS
This study demonstrates that the elbow method provides a credible prediction for both gene expression data and for precisely estimating simulated mutational processes data with known dimensions. The proposed UIK method is faster than conventional methods, including metrics utilizing the consensus matrix as a criterion for rank selection, while achieving significantly better computational efficiency without visual inspection on the curvatives. Finally, the suggested rank tuning method based on the elbow method for gene expression data is arguably theoretically superior to the cophenetic measure.
PubMed: 38935969
DOI: 10.2196/43665 -
JMIR Bioinformatics and Biotechnology May 2024Genetic data are widely considered inherently identifiable. However, genetic data sets come in many shapes and sizes, and the feasibility of privacy attacks depends on... (Review)
Review
BACKGROUND
Genetic data are widely considered inherently identifiable. However, genetic data sets come in many shapes and sizes, and the feasibility of privacy attacks depends on their specific content. Assessing the reidentification risk of genetic data is complex, yet there is a lack of guidelines or recommendations that support data processors in performing such an evaluation.
OBJECTIVE
This study aims to gain a comprehensive understanding of the privacy vulnerabilities of genetic data and create a summary that can guide data processors in assessing the privacy risk of genetic data sets.
METHODS
We conducted a 2-step search, in which we first identified 21 reviews published between 2017 and 2023 on the topic of genomic privacy and then analyzed all references cited in the reviews (n=1645) to identify 42 unique original research studies that demonstrate a privacy attack on genetic data. We then evaluated the type and components of genetic data exploited for these attacks as well as the effort and resources needed for their implementation and their probability of success.
RESULTS
From our literature review, we derived 9 nonmutually exclusive features of genetic data that are both inherent to any genetic data set and informative about privacy risk: biological modality, experimental assay, data format or level of processing, germline versus somatic variation content, content of single nucleotide polymorphisms, short tandem repeats, aggregated sample measures, structural variants, and rare single nucleotide variants.
CONCLUSIONS
On the basis of our literature review, the evaluation of these 9 features covers the great majority of privacy-critical aspects of genetic data and thus provides a foundation and guidance for assessing genetic data risk.
PubMed: 38935957
DOI: 10.2196/54332 -
JMIR Cancer Jun 2024Many supportive cancer care (SCC) services were teledelivered during COVID-19, but what facilitates patients' intentions to use teledelivered SCC is unknown.
Applying the Unified Theory of Acceptance and Use of Technology to Identify Factors Associated With Intention to Use Teledelivered Supportive Care Among Recently Diagnosed Breast Cancer Survivors During COVID-19 in Hong Kong: Cross-Sectional Survey.
BACKGROUND
Many supportive cancer care (SCC) services were teledelivered during COVID-19, but what facilitates patients' intentions to use teledelivered SCC is unknown.
OBJECTIVE
The study aimed to use the unified theory of acceptance and use of technology to investigate the factors associated with the intentions of breast cancer survivors (BCS) in Hong Kong to use various types of teledelivered SCC (including psychosocial care, medical consultation, complementary care, peer support groups). Favorable telehealth-related perceptions (higher performance expectancy, lower effort expectancy, more facilitating conditions, positive social influences), less technological anxiety, and greater fear of COVID-19 were hypothesized to be associated with higher intentions to use teledelivered SCC. Moreover, the associations between telehealth-related perceptions and intentions to use teledelivered SCC were hypothesized to be moderated by education level, such that associations between telehealth-related perceptions and intentions to use teledelivered SCC would be stronger among those with a higher education level.
METHODS
A sample of 209 (209/287, 72.8% completion rate) women diagnosed with breast cancer since the start of the COVID-19 outbreak in Hong Kong (ie, January 2020) were recruited from the Hong Kong Breast Cancer Registry to complete a cross-sectional survey between June 2022 and December 2022. Participants' intentions to use various types of teledelivered SCC (dependent variables), telehealth-related perceptions (independent variables), and sociodemographic variables (eg, education, as a moderator variable) were measured using self-reported, validated measures.
RESULTS
Hierarchical regression analysis results showed that greater confidence using telehealth, performance expectancy (believing telehealth helps with daily tasks), social influence (important others encouraging telehealth use), and facilitating conditions (having resources for telehealth use) were associated with higher intentions to use teledelivered SCC (range: β=0.16, P=.03 to β=0.34, P<.001). Moreover, 2-way interactions emerged between education level and 2 of the telehealth perception variables. Education level moderated the associations between (1) performance expectancy and intention to use teledelivered complementary care (β=0.34, P=.04) and (2) facilitating conditions and intention to use teledelivered peer support groups (β=0.36, P=.03). The positive associations between those telehealth perceptions and intentions were only significant among those with a higher education level.
CONCLUSIONS
The findings of this study implied that enhancing BCS' skills at using telehealth, BCS' and their important others' perceived benefits of telehealth, and providing assistance for telehealth use could increase BCS' intentions to use teledelivered SCC. For intentions to use specific types of SCC, addressing relevant factors (performance expectancy, facilitating conditions) might be particularly beneficial for those with a higher education level.
PubMed: 38935942
DOI: 10.2196/51072