Nevin Manimala

Vet Rec. 2022 Aug 27:e2031. doi: 10.1002/vetr.2031. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to assess the risk of bilateral disease in dogs affected by spontaneous chronic corneal epithelial defects (SCCEDs) and identify any recent changes in the distribution of breeds affected.

METHODS: Medical records of dogs assessed at a single ophthalmic centre for the management of SCCEDs between 2007 and 2020 were reviewed, and clinical data were extracted.

RESULTS: Three hundred and seven dogs met the inclusion criteria. Boxers (129 dogs), Staffordshire Bull Terriers (37 dogs) and French Bulldogs (20 dogs) were most frequently affected. Overall, the median age at presentation was 8 years (range 1-15 years), but French Bulldogs had a younger median age of 6 years. Boxers, French Bulldogs and Staffordshire Bull Terriers showed higher odds of bilateral ulceration (odds ratio 1.79, 1.65 and 1.64, respectively) compared to the overall study population. The median time between presentations when both eyes were affected was 4 months (range 0-42 months). There was a statistically significant increase in French Bulldogs, a reduction in Boxers and a stable number of Staffordshire Bull Terriers treated for this condition. However, as the effective sample size from each individual breed was small, further studies would be beneficial to confirm these findings.

CONCLUSION: The results from this study suggest a shift in breed distribution. The risk of bilateral disease is higher in the three breeds reported here, and owners should be counselled appropriately at the initial examination.

PMID:36030371 | DOI:10.1002/vetr.2031

Eur Spine J. 2022 Aug 27. doi: 10.1007/s00586-022-07358-w. Online ahead of print.

NO ABSTRACT

PMID:36030349 | DOI:10.1007/s00586-022-07358-w

Nat Commun. 2022 Aug 27;13(1):5047. doi: 10.1038/s41467-022-32626-0.

ABSTRACT

DNA points accumulation for imaging in nanoscale topography (DNA-PAINT) is a super-resolution technique with relatively easy-to-implement multi-target imaging. However, image acquisition is slow as sufficient statistical data has to be generated from spatio-temporally isolated single emitters. Here, we train the neural network (NN) DeepSTORM to predict fluorophore positions from high emitter density DNA-PAINT data. This achieves image acquisition in one minute. We demonstrate multi-colour super-resolution imaging of structure-conserved semi-thin neuronal tissue and imaging of large samples. This improvement can be integrated into any single-molecule imaging modality to enable fast single-molecule super-resolution microscopy.

PMID:36030338 | DOI:10.1038/s41467-022-32626-0

Ther Innov Regul Sci. 2022 Aug 27. doi: 10.1007/s43441-022-00450-9. Online ahead of print.

ABSTRACT

Use of robust, quantitative tools to measure patient perspectives within product development and regulatory review processes offers the opportunity for medical device researchers, regulators, and other stakeholders to evaluate what matters most to patients and support the development of products that can best meet patient needs. The medical device innovation consortium (MDIC) undertook a series of projects, including multiple case studies and expert consultations, to identify approaches for utilizing patient preference information (PPI) to inform clinical trial design in the US regulatory context. Based on these activities, this paper offers a cogent review of considerations and opportunities for researchers seeking to leverage PPI within their clinical trial development programs and highlights future directions to enhance this field. This paper also discusses various approaches for maximizing stakeholder engagement in the process of incorporating PPI into the study design, including identifying novel endpoints and statistical considerations, crosswalking between attributes and endpoints, and applying findings to the population under study. These strategies can help researchers ensure that clinical trials are designed to generate evidence that is useful to decision makers and captures what matters most to patients.

PMID:36030334 | DOI:10.1007/s43441-022-00450-9

Pediatr Res. 2022 Aug 27. doi: 10.1038/s41390-022-02272-9. Online ahead of print.

ABSTRACT

BACKGROUND: Low levels of insulin-like growth factor-1 (IGF-1) protein in preterm human infants are associated with bronchopulmonary dysplasia (BPD). We used our preterm lamb model of BPD to determine (1) dosage of recombinant human (rh) IGF-1 bound to binding protein-3 (IGFBP-3) to reach infant physiologic plasma levels; and (2) whether repletion of plasma IGF-1 improves pulmonary and cardiovascular outcomes.

METHODS: Group 1: normal, unventilated lambs from 128 days gestation through postnatal age 5 months defined normal plasma levels of IGF-1. Group 2: continuous infusion of rhIGF-1/rhIGFBP-3 (0.5, 1.5, or 4.5 mg/kg/day; n = 2) for 3 days in mechanically ventilated (MV) preterm lambs determined that 1.5 mg/kg/day dosage attained physiologic plasma IGF-1 concentration of ~125 ng/mL, which was infused in four more MV preterm lambs.

RESULTS: Group 1: plasma IGF-1 protein increased from ~75 ng/mL at 128 days gestation to ~220 ng/L at 5 months. Group 2: pilot study of the optimal dosage (1.5 mg/kg/day rhIGF-1/rhIGFBP-3) in six MV preterm lambs significantly improved some pulmonary and cardiovascular outcomes (p < 0.1) compared to six MV preterm controls. RhIGF-1/rhIGFBP-3 was not toxic to the liver, kidneys, or lungs.

CONCLUSIONS: Three days of continuous iv infusion of rhIGF-1/rhIGFBP-3 at 1.5 mg/kg/day improved some pulmonary and cardiovascular outcomes without toxicity.

IMPACT: Preterm birth is associated with rapid decreases in serum or plasma IGF-1 protein level. This decline adversely impacts the growth and development of the lung and cardiovascular system. For this pilot study, continuous infusion of optimal dosage of rhIGF-1/rhIGFBP-3 (1.5 mg/kg/day) to maintain physiologic plasma IGF-1 level of ~125 ng/mL during mechanical ventilation for 3 days statistically improved some structural and biochemical outcomes related to the alveolar formation that would favor improved gas exchange compared to vehicle-control. We conclude that 3 days of continuous iv infusion of rhIGF-1/rhIGFBP-3 improved some physiological, morphological, and biochemical outcomes, without toxicity, in mechanically ventilated preterm lambs.

PMID:36030318 | DOI:10.1038/s41390-022-02272-9

Sci Rep. 2022 Aug 27;12(1):14635. doi: 10.1038/s41598-022-18838-w.

ABSTRACT

The lack of invariance problem in speech perception refers to a fundamental problem of how listeners deal with differences of speech sounds produced by various speakers. The current study is the first to test the contributions of mentally stored distributional information in normalization of prosodic cues. This study starts out by modelling distributions of acoustic cues from a speech corpus. We proceeded to conduct three experiments using both naturally produced lexical tones with estimated distributions and manipulated lexical tones with f0 values generated from simulated distributions. State of the art statistical techniques have been used to examine the effects of distribution parameters in normalization and identification curves with respect to each parameter. Based on the significant effects of distribution parameters, we proposed a probabilistic parametric representation (PPR), integrating knowledge from previously established distributions of speakers with their indexical information. PPR is still accessed during speech perception even when contextual information is present. We also discussed the procedure of normalization of speech signals produced by unfamiliar talker with and without contexts and the access of long-term stored representations.

PMID:36030274 | DOI:10.1038/s41598-022-18838-w

Nat Commun. 2022 Aug 27;13(1):5062. doi: 10.1038/s41467-022-32477-9.

ABSTRACT

A major obstacle in diabetes is the metabolic or hyperglycemic memory, which lacks specific therapies. Here we show that glucose-mediated changes in gene expression largely persist in diabetic kidney disease (DKD) despite reversing hyperglycemia. The senescence-associated cyclin-dependent kinase inhibitor p21 (Cdkn1a) was the top hit among genes persistently induced by hyperglycemia and was associated with induction of the p53-p21 pathway. Persistent p21 induction was confirmed in various animal models, human samples and in vitro models. Tubular and urinary p21-levels were associated with DKD severity and remained elevated despite improved blood glucose levels in humans. Mechanistically, sustained tubular p21 expression in DKD is linked to demethylation of its promoter and reduced DNMT1 expression. Two disease resolving agents, protease activated protein C (3K3A-aPC) and parmodulin-2, reversed sustained tubular p21 expression, tubular senescence, and DKD. Thus, p21-dependent tubular senescence is a pathway contributing to the hyperglycemic memory, which can be therapeutically targeted.

PMID:36030260 | DOI:10.1038/s41467-022-32477-9

Clin Epigenetics. 2022 Aug 27;14(1):107. doi: 10.1186/s13148-022-01323-6.

ABSTRACT

Nanopore sequencing has brought the technology to the next generation in the science of sequencing. This is achieved through research advancing on: pore efficiency, creating mechanisms to control DNA translocation, enhancing signal-to-noise ratio, and expanding to long-read ranges. Heterogeneity regarding epigenetics would be broad as mutations in the epigenome are sensitive to cause new challenges in cancer research. Epigenetic enzymes which catalyze DNA methylation and histone modification are dysregulated in cancer cells and cause numerous heterogeneous clones to evolve. Detection of this heterogeneity in these clones plays an indispensable role in the treatment of various cancer types. With single-cell profiling, the nanopore sequencing technology could provide a simple sequence at long reads and is expected to be used soon at the bedside or doctor’s office. Here, we review the advancements of nanopore sequencing and its use in the detection of epigenetic heterogeneity in cancer.

PMID:36030244 | DOI:10.1186/s13148-022-01323-6

BMC Neurosci. 2022 Aug 27;23(1):51. doi: 10.1186/s12868-022-00737-5.

ABSTRACT

BACKGROUND: Spinal cord injury (SCI) is a common trauma in clinical practices. Subacute SCI is mainly characterized by neuronal apoptosis, axonal demyelination, Wallerian degeneration, axonal remodeling, and glial scar formation. It has been discovered in recent years that inflammatory responses are particularly important in subacute SCI. However, the mechanisms mediating inflammation are not completely clear.

METHODS: The gene expression profiles of GSE20907, GSE45006, and GSE45550 were downloaded from the GEO database. The models of the three gene expression profiles were all for SCI to the thoracic segment of the rat. The differentially expressed genes (DEGs) and weighted correlation network analysis (WGCNA) were performed using R software, and functional enrichment analysis and protein-protein interaction (PPI) network were performed using Metascape. Module analysis was performed using Cytoscape. Finally, the relative mRNA expression level of central genes was verified by RT-PCR.

RESULTS: A total of 206 candidate genes were identified, including 164 up-regulated genes and 42 down-regulated genes. The PPI network was evaluated, and the candidate genes enrichment results were mainly related to the production of tumor necrosis factors and innate immune regulatory response. Twelve core genes were identified, including 10 up-regulated genes and 2 down-regulated genes. Finally, seven hub genes with statistical significance in both the RT-PCR results and expression matrix were identified, namely Itgb1, Ptprc, Cd63, Lgals3, Vav1, Shc1, and Casp4. They are all related to the activation process of microglia.

CONCLUSION: In this study, we identified the hub genes and signaling pathways involved in subacute SCI using bioinformatics methods, which may provide a molecular basis for the future treatment of SCI.

PMID:36030234 | DOI:10.1186/s12868-022-00737-5

Int J Equity Health. 2022 Aug 27;21(1):118. doi: 10.1186/s12939-022-01713-5.

ABSTRACT

BACKGROUND: Measuring health inequality is essential to ensure that everyone has equal accessibility to health care. Studies in the past have continuously presented and showed areas or groups of people affected by various inequality in accessing the health resources and services to help improve this matter. Alongside, disease prevention is as important to minimise the disease burden and improve health and quality of life. These aspects are interlinked and greatly contributes to one’s health.

METHOD: In this study, the Gini coefficient and Lorenz curve are used to give an indication of the overall health inequality. The impact of this inequality in granular level is demonstrated using Bayesian estimation for disease detection. The Bayesian estimation used a two-component modelling approach that separates the case detection process and incidence rate using a mixed Poisson distribution while capturing underlying spatio-temporal characteristics. Bayesian model averaging is used in conjunction with the two-component modelling approach to improve the accuracy of estimates by incorporating many candidate models into the analysis instead of using fixed component models. This method is applied to an infectious disease, influenza, in Victoria, Australia between 2013 and 2016 and the corresponding primary health care of the state.

RESULT: There is a relatively equal distribution of health resources and services pertaining to general practitioners (GP) and GP clinics in Victoria, Australia. Roughly 80 percent of the population shares 70 percent of the number of GPs and GP clinics. The Bayesian estimation with model averaging revealed that access difficulty to health services impacts both case detection probability and incidence rate. Minimal differences are recorded in the observed and estimated incidence of influenza cases considering social deprivation factors. In most years, areas in Victoria’s southwest and eastern parts have potential under-reported cases consistent with their relatively lower number of GP or GP clinics.

CONCLUSION: The Bayesian model estimated a slight discrepancy between the estimated incidence and the observed cases of influenza in Victoria, Australia in 2013-2016 period. This is consistent with the relatively equal health resources and services in the state. This finding is beneficial in determining areas with potential under-reported cases and under-served health care. The proposed approach in this study provides insight into the impact of health inequality in disease detection without requiring costly and time-extensive surveys and relying mainly on the data at hand. Furthermore, the application of Bayesian model averaging provided a flexible modelling framework that allows covariates to move between case detection and incidence models.

PMID:36030233 | DOI:10.1186/s12939-022-01713-5