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Clinical Ophthalmology (Auckland, N.Z.) 2024To report the outcomes of using a sutureless human amniotic membrane dehydrated matrix (HAMDM) in the management of a range of ocular surface conditions utilizing a...
Management of Ocular Surface Inflammation with Persistent Epithelial Defects Using a Sutureless Human Amniotic Membrane Dehydrated Matrix: A Prospective Study Utilizing a Digital Ocular Surface Assessment Tool.
PURPOSE
To report the outcomes of using a sutureless human amniotic membrane dehydrated matrix (HAMDM) in the management of a range of ocular surface conditions utilizing a digital ocular surface disease assessment tool.
METHODS
Two UK NHS Trusts - Queen Victoria Hospital Foundation Trust (East Grinstead and Maidstone) and Tunbridge Wells Trust (Kent) - prospectively treated patients with ocular surface disease with sutureless HAMDM. The patient cohort was assessed for resolution of epithelial defects, ocular surface inflammation, and best-corrected visual acuity pre- and posttreatment. Measurements of ocular surface inflammation and epithelial defect size were assessed using AOS digital imaging software, a validated tool for objective grading of bulbar conjunctival redness and measurement of corneal epithelial defects.
RESULTS
A total of 47 applications of sutureless HAMDM on 46 eyes of 46 patients (25 male, 21 female, age 9-94 years) were assessed across various etiologies for an average of 24.0±14.1 days. Patients with limbal stem-cell deficiency (n=17), persistent epithelial defects (n=16), neurotrophic corneal disease (n=7), filamentary keratitis (n=2), corneal erosion (n=1), corneal thinning (n=1), ocular surface inflammation (n=1), and traumatic corneal laceration (n=1) were included in the study. Across all patents, 63% of eyes showed complete healing of epithelial defects and 32.6% of eyes showed partial resolution. The average rate of healing (wound closure) was 0.36 mm per day across the overall patient cohort, and the rate of healing in cases with complete resolution of epithelial defects was 0.41 mm per day. Inflammation across all four quadrants of the ocular surface remained stable. Visual acuity across the patient cohort remained stable (61%) and improved in 26% of patients (0.06±0.51 logMAR).
CONCLUSION
Sutureless HAMDM application can be accomplished in just a few minutes and effectively treat a range of ocular surface disease in a clinical, nonsurgical setting. The AOS imaging software offered a quantitative methodology for measuring epithelial defect size and inflammation state.
PubMed: 38813539
DOI: 10.2147/OPTH.S456864 -
Health Science Reports Jun 2024Severe acute malnutrition remains a significant health challenge, particularly in low- and middle-income countries. The aim of this study was to determine the survival...
BACKGROUND AND AIMS
Severe acute malnutrition remains a significant health challenge, particularly in low- and middle-income countries. The aim of this study was to determine the survival time of under-five children with severe acute malnutrition.
METHODS
A retrospective cohort study was conducted at a hospital, focusing on under-five children with severe acute malnutrition. The study included 322 inpatients admitted to the Chiro hospital in Chiro, Ethiopia, between September 2019 and August 2020, whose data was obtained from medical records. Survival functions were analysed using Kaplan‒Meier plots and log-rank tests. The survival time of severe acute malnutrition was further analysed using the Cox proportional hazards model and Bayesian parametric survival models, employing integrated nested Laplace approximation methods.
RESULTS
Among the 322 patients, 118 (36.6%) died as a result of severe acute malnutrition. The estimated median survival time for inpatients was found to be 2 weeks. Model selection criteria favored the Bayesian Weibull accelerated failure time model, which demonstrated that age, body temperature, pulse rate, nasogastric (NG) tube usage, hypoglycemia, anemia, diarrhea, dehydration, malaria, and pneumonia significantly influenced the survival time of severe acute malnutrition.
CONCLUSIONS
This study revealed that children below 24 months, those with altered body temperature and pulse rate, NG tube usage, hypoglycemia, and comorbidities such as anemia, diarrhea, dehydration, malaria, and pneumonia had a shorter survival time when affected by severe acute malnutrition under the age of five. To reduce the death rate of children under 5 years of age, it is necessary to design community management for acute malnutrition to ensure early detection and improve access to and coverage for children who are malnourished.
PubMed: 38812715
DOI: 10.1002/hsr2.2135 -
Drug Metabolism and Disposition: the... May 2024Cantharidin is a terpenoid from coleoptera beetles. Cantharidin has been used to treat molluscum contagiosum and some types of tumors. Cantharidin is highly toxic and...
Cantharidin is a terpenoid from coleoptera beetles. Cantharidin has been used to treat molluscum contagiosum and some types of tumors. Cantharidin is highly toxic and cantharidin poisoning and fatal cases have been reported worldwide. The mechanisms underlying cantharidin-induced toxicity remain unclear. Cantharidin contains anhydride, which may react with biological amines. This study aimed to examine the chemical reactivity of cantharidin toward nucleophiles and characterize adducts of cantharidin with biological amines and in mice. Here, two types of conjugates were formed in the incubation of cantharidin under physiologic conditions with free amino acids, a mimic peptide, or amine-containing compounds, respectively. Amide-type conjugates were produced by the binding of cantharidin anhydride with the primary amino group of biological amines. Imide-type conjugates were generated from the dehydration and cyclization of amide-type conjugates. The structure of the conjugates was characterized by using the high-resolution mass spectrometry. We introduced the N/N and Br/Br isotope signatures to confirm the formation of conjugates using L-(ε)N-lysine, L-lysine-N, and bromine-tagged hydrazine, respectively. The structure of imide conjugate was also confirmed by NMR experiments. Furthermore, the amide and imide conjugates of cantharidin with amino acids or -acetyl-lysine were detected in mouse liver and urine. Cantharidin was found to modify lysine residue proteins in mouse liver. Pan-P450 inhibitor 1-aminobenzotriazole significantly increased the urine cantharidin--acetyl-lysine conjugates whereas decreased cantharidin metabolites. In summary, cantharidin anhydride can covalently bind to biological amines nonenzymatically, which facilitates a better understanding of the role of nonenzymatic reactivity in cantharidin poisoning. Anhydride moiety of cantharidin can covalently bind to the primary amino group of biological amines nonenzymatically. Amide and imide conjugates were generated after the covalent binding of cantharidin anhydride with the primary amino groups of amino acids, a mimic peptide, and protein lysine residues. The structure of conjugates was confirmed by N/N and Br/Br isotope signatures using isotope-tagged reagents and NMR experiments. This study will facilitate the understanding of the role of nonenzymatic reactivity in cantharidin poisoning.
PubMed: 38811155
DOI: 10.1124/dmd.123.001637 -
Science Advances May 2024Methane-derived authigenic carbonate often constitutes the sole remaining record of relic methane seeps. The clumped (∆) and oxygen isotopic composition of seep...
Methane-derived authigenic carbonate often constitutes the sole remaining record of relic methane seeps. The clumped (∆) and oxygen isotopic composition of seep carbonates often yield inaccurate temperatures, attributed to kinetic isotope effects and modification of seawater isotope composition by hydrate water. Here, we analyzed the dual-clumped isotope (∆/∆) composition of authigenic carbonate from a modern methane seep. We demonstrate that aragonite forms closest to isotopic equilibrium such that its ∆ can directly yield the correct formational temperature, whereas calcite is unambiguously biased by kinetic isotope effects. Numerical models show that the observed bias in the isotopic composition arises from rate-limiting dehydration/dehydroxylation of HCO alongside diffusive fractionation, which can be corrected for with analysis of carbonate ∆/∆ values. We demonstrate the utility of dual-clumped isotope analysis for studying seep carbonates, as it reveals the origin and magnitude of kinetic biases and can be used to reconstruct paleotemperature and seawater δO.
PubMed: 38809987
DOI: 10.1126/sciadv.adn0155 -
Current Research in Food Science 2024In this paper, we describe a model for pore formation in food materials during drying. As a proxy for fruits and vegetables, we take a spherical hydrogel, with a stiff...
In this paper, we describe a model for pore formation in food materials during drying. As a proxy for fruits and vegetables, we take a spherical hydrogel, with a stiff elastic skin, and a central cavity filled with air and water vapour. The model describes moisture transport coupled to large deformation mechanics. Both stress and chemical potential are derived from a free energy functional, following the framework developed by Suo and coworkers. We have compared Finite Volume and Finite Element implementations and analytical solutions with each other, and we show that they render similar solutions. The Finite Element solver has a larger range of numerical stability than the Finite Volume solver, and the analytical solution also has a limited range of validity. Since the Finite Element solver operates using the mathematically intricate weak form, we introduce the method in a tutorial manner for food scientists. Subsequently, we have explored the physics of the pore formation problem further with the Finite Element solver. We show that the presence of an elastic skin is a prerequisite for the growth of the central cavity. The elastic skin must have an elastic modulus of at least 10 times that of the hydrogel. An initial pore with 10% of the size of the gel can grow to 5 times its initial size. Such an increase in porosity has been reported in the literature on drying of vegetables, if a dense hard skin is formed, known as case hardening. We discuss that models as presented in this paper, where moisture transport is strongly coupled to large deformation mechanics, are required if one wants to describe pore/structure formation during drying and intensive heating (as baking and frying) of food materials from first principles.
PubMed: 38808328
DOI: 10.1016/j.crfs.2024.100762 -
Scientific Reports May 2024Stress drop is an earthquake property indicative for the characteristic relation of slip to fault dimension. It is furthermore affected by fault strength, fault...
Stress drop is an earthquake property indicative for the characteristic relation of slip to fault dimension. It is furthermore affected by fault strength, fault topography, the presence of fluids, rupture size, slip, and velocity. In this article, the stress drop image of an entire subduction zone, namely for the seismically highly active northernmost part of Chile, is combined with mapped b-values and their corresponding magnitude distribution in order to better constrain the conditions under which earthquakes of different provenances may nucleate. The underlying recent earthquake catalog contains over 180,000 events, covering 15 years of seismicity, from which more than 50,000 stress drop estimates were computed. Their spatial average segments the subduction zone into different parts, i.e., average stress drop between seismotectonic areas is different, although this difference is small compared to the natural scatter of stress drop values. By considering stress drop variations, b-value map, magnitude distribution, and thermal models, candidate earthquake nucleation mechanisms are identified which can explain the observed distributions. This is done for two exemplary regions: (1) The plate interface, where principally lower stress drop events are found, while at the same time a high spatial heterogeneity of stress drop values is observed. This indicates relatively smooth or lubricated rupture surfaces, and locally it suggests the existence of alternating regions controlled by strong asperities, weaker material, or creep. (2) The highly active intermediate depth (ID) seismicity region, where the variation of stress drop and b-value point to a gradual change of nucleation mechanism from dehydration embrittlement at the top of the ID cloud, over dehydration driven stress transfer in its central part, to thermal runaway shear mechanisms at its bottom. In both cases, the combination of stress drop and b-value distribution helps to better understand the origin and the differences of the observed seismicity.
PubMed: 38806618
DOI: 10.1038/s41598-024-63015-w -
International Journal of Food Science 2024The beans' protein and slow-digesting carbohydrate content make it an appealing choice for healthy food development. However, its properties are influenced by the flour...
The beans' protein and slow-digesting carbohydrate content make it an appealing choice for healthy food development. However, its properties are influenced by the flour extraction processes. This study is aimed at evaluating the effect of particle size and three pretreatments-drying (D), soaking + cooking + dehydrating 3 h (SCD3), and soaking + cooking + dehydrating 24 h (SCD24)-on the estimated glycemic index (eGI) compared with raw bean flour (R). The methodology covered water absorption (WAI), water solubility (WSI), amylose content, starch digestibility, eGI, phenolic quantification, and rheology. The results showed that WAI correlated negatively with WSI and amylose, varying among pretreatments and sizes. WAI increased as D < SCD24 < SCD3 < R. Glucose release (HI) differed between fine (125 m) and coarse fractions (242 m), with SCD24 and R showing the lowest eGI (22.8-24.2). SCD3 had the highest flavonoid concentration, while R and D had more quercetin-3-glucoside. SCD24 displayed higher elastic/viscous moduli than R. Bean flours from all treatments had low GI and contained bioactive polyphenols (catechin, epicatechin, ferulic acid, quercetin). The optimal treatment was SCD24, particularly in the coarse fraction, showing potential for functional food development and novel applications such as precision nutrition.
PubMed: 38803398
DOI: 10.1155/2024/6336837 -
Biophysics and Physicobiology 2024Deposition and accumulation of amyloid fibrils is a hallmark of a group of diseases called amyloidosis and neurodegenerative disorders. Although polypeptides potentially...
Deposition and accumulation of amyloid fibrils is a hallmark of a group of diseases called amyloidosis and neurodegenerative disorders. Although polypeptides potentially have a fibril-forming propensity, native proteins have evolved into proper functional conformations to avoid aggregation and fibril formation. Understanding the mechanism for regulation of fibril formation of native proteins provides clues for the rational design of molecules for inhibiting fibril formation. Although fibril formation is a complex multistep reaction, experimentally obtained fibril formation curves can be fitted with the Finke-Watzky (F-W) two-step model for homogeneous nucleation followed by autocatalytic fibril growth. The resultant F-W rate constants for nucleation and fibril formation provide information on the chemical kinetics of fibril formation. Using the F-W two-step model analysis, we investigated the physicochemical mechanisms of fibril formation of a Parkinson's disease protein α-synuclein (αS) and a systemic amyloidosis protein apolipoprotein A-I (apoA-I). The results indicate that the C-terminal region of αS enthalpically and entropically suppresses nucleation through the intramolecular interaction with the N-terminal region and the intermolecular interaction with existing fibrils. In contrast, the nucleation of the N-terminal fragment of apoA-I is entropically driven likely due to dehydration of large hydrophobic segments in the molecule. Based on our recent findings, we discuss the similarity and difference of the fibril formation mechanisms of αS and the N-terminal fragment of apoA-I from the physicochemical viewpoints.
PubMed: 38803339
DOI: 10.2142/biophysico.bppb-v21.0005 -
EClinicalMedicine Jun 2024Diarrhoeal disease poses a significant global health challenge, especially in children under three years old. Despite the effectiveness of oral rehydration therapy...
Assessing safety and efficacy of a novel glucose-free amino acid oral rehydration solution for watery diarrhea management in children: a randomized, controlled, phase III trial.
BACKGROUND
Diarrhoeal disease poses a significant global health challenge, especially in children under three years old. Despite the effectiveness of oral rehydration therapy (ORT), its adoption remains low. Glucose-based ORS (GORS) is the standard, but novel formulations like glucose-free amino acid-based VS002A have emerged as potential alternatives. This study aimed to compare the safety and efficacy of VS002A against the standard WHO-ORS in treating non-cholera acute watery diarrhoea in children.
METHODS
A triple-blind, randomized trial enrolled 310 male infants and children aged 6-36 months, who were assigned to receive WHO-ORS or VS002A over a 16-month period, from June 2021 to September 2022. Both groups received standard of care, including zinc supplementation. The Primary study outcome measured was the duration of diarrhoea. Secondary outcomes included stool output, treatment failure and adverse events. Exploratory endpoints included urinary output, body weight changes, blood biochemistry, stool microbiology and gut health biomarkers.
FINDINGS
Both VS002A and WHO-ORS were well-tolerated with a low adverse event rate. While not different statistically (p = 0.10), duration of diarrhoea was shorter in children treated with VS002A vs. WHO-ORS (65.4 h vs. 72.6 h). Similarly, stool output was also lower vs. WHO-ORS in children treated with VS002A, though not statistically different (p = 0.40). Serum citrulline levels, an indicator of gut health, were higher in the VS002A group at 24 h suggesting a potential protective effect (p = 0.06).
INTERPRETATION
The findings of this study support the non-inferiority of VS002A, a glucose-free amino acid-based ORS compared to the WHO-ORS standard of care. VS002A was shown to be safe and effective in treating non-cholera acute watery diarrhoea in young children. VS002A may offer advantages in pathogen-driven diarrhoea, supported by trends toward a lower duration of diarrhoea and stool output within the per protocol group. Furthermore, individuals with prolonged diarrhoea, severe malnutrition, environmental enteric dysfunction or have issues with obesity or insulin resistance, could benefit from a glucose-free ORS. This research contributes to addressing the persistent challenge of childhood diarrhoea by presenting an alternative glucose-free ORS formulation with potential advantages in select scenarios, offering a promising avenue for improving paediatric diarrhoea management worldwide.
FUNDING
The study was funded by Entrinsic Bioscience, LLC., Norwood, MA, USA.
PubMed: 38800804
DOI: 10.1016/j.eclinm.2024.102630 -
Frontiers in Microbiology 2024Porcine viral diarrhea is caused by many pathogens and can result in watery diarrhea, dehydration and death. Various detection methods, such as polymerase chain reaction...
Development of a triplex quantitative reverse transcription-polymerase chain reaction for the detection of porcine epidemic diarrhea virus, porcine transmissible gastroenteritis virus, and porcine rotavirus A.
Porcine viral diarrhea is caused by many pathogens and can result in watery diarrhea, dehydration and death. Various detection methods, such as polymerase chain reaction (PCR) and real-time quantitative PCR (qPCR), have been widely used for molecular diagnosis. We developed a triplex real-time quantitative reverse transcription PCR (qRT-PCR) for the simultaneous detection of three RNA viruses potentially associated with porcine viral diarrhea: porcine epidemic diarrhea virus (PEDV), porcine transmissible gastroenteritis virus (TGEV), and porcine rotavirus A (PoRVA). The triplex qRT-PCR had values of 0.999 for the standard curves of PEDV, TGEV and PoRVA. Importantly, the limits of detection for PEDV, TGEV and PoRVA were 10 copies/μL. The specificity test showed that the triplex qRT-PCR detected these three pathogens specifically, without cross-reaction with other pathogens. In addition, the approach had good repeatability and reproducibility, with intra-and inter-assay coefficients of variation <1%. Finally, this approach was evaluated for its practicality in the field using 256 anal swab samples. The positive rates of PEDV, TGEV and PoRVA were 2.73% (7/256), 3.91% (10/256) and 19.14% (49/256), respectively. The co-infection rate of two or more pathogens was 2.73% (7/256). The new triplex qRT-PCR was compared with the triplex RT-PCR recommended by the Chinese national standard (GB/T 36871-2018) and showed 100% agreement for PEDV and TGEV and 95.70% for PoRVA. Therefore, the triplex qRT-PCR provided an accurate and sensitive method for identifying three potential RNA viruses for porcine viral diarrhea that could be applied to diagnosis, surveillance and epidemiological investigation.
PubMed: 38800746
DOI: 10.3389/fmicb.2024.1390328