Nevin Manimala

Exp Dermatol. 2021 Nov 2. doi: 10.1111/exd.14488. Online ahead of print.

ABSTRACT

Tissue engineering has been successful in reproducing human skin equivalents while incorporating new approaches such as three-dimensional (3D) bioprinting. The latter method offers a plethora of advantages including increased production scale, ability to incorporate multiple cell types, and printing on demand. However, the quality of printed skin equivalents compared to those developed manually has never been assessed. To leverage the benefits of this method, it is imperative that 3D printed skin should be structurally and functionally similar to real human skin. Here, we developed four bilayered human skin epidermal-dermal equivalents: non-printed dermis and epidermis (NN), printed dermis and epidermis (PP), printed epidermis and non-printed dermis (PN), and non-printed epidermis and printed dermis (NP). The effects of printing induced shear stress [0.025 kPa (epidermis); 0.049 kPa (dermis)] were characterized both at the cellular and at the tissue level. At cellular level, no statistically significant differences in keratinocyte colony forming efficiency (CFE) (p=0.1641), was observed. In the case of fibroblasts, no significant differences in the cell alignment index (p<0.1717), and their ability to contract collagen gel (p=0.851) were detected. At the tissue levels, all the four skin equivalents were characterized using histological and immunohistochemical analysis with no significant differences found in either epidermal basal cell count, thickness of viable epidermis, and relative intensity of filaggrin and claudin-1. Our results demonstrated that 3D printing can achieve the same high-quality skin constructs as have been developed traditionally, thus opening new avenues for numerous high-throughput industrial and clinical applications.

PMID:34727395 | DOI:10.1111/exd.14488

Int J Dev Neurosci. 2021 Nov 2. doi: 10.1002/jdn.10155. Online ahead of print.

ABSTRACT

Maternal separation (MS) is a model to induce permanent alternations in the central nervous system (CNS) and is associated with increased levels of anxiety and cognitive deficiencies. Since Methyl donor choline (Ch) has been shown to play a significant role in learning and memory and enhances synaptic plasticity, the authors hypothesized that Ch may attenuate MS-induced impairments in synaptic plasticity and cognitive performance. Rat pups underwent a MS protocol for 180 min/day from postnatal day (PND) 1 to 21. Ch was administered subcutaneously (100 mg/kg, 21 days) to the Choline chloride and MS + Choline chloride groups from PND 29 to 49. Anxiety-like behavior, recognition memory, spatial and passive avoidance learning and memory were measured in the adolescent rats. In addition, evoked field excitatory postsynaptic potentials (fEPSP) were recorded from the CA1 region of the hippocampus. MS induced higher anxiety-like behavior in the animals. It also impaired learning and memory. However, MS had no effect on locomotor activity. Subcutaneous administration of Ch attenuated MS-induced cognitive deficits and enhanced the learning and memory of MS rats. Ch also decreased anxiety-like behavior in the open field test. The present results showed that long-term potentiation (LTP) was induced in all groups except MS and MS + saline animals. However, Ch injection induced LTP and had maintenance in MS + choline chloride, but it was not statistically significant compared with the MS group. In summary, the present findings indicate that MS can interfere with normal animal’s cognition and subcutaneous of Ch may be considered an appropriate therapeutic strategy for promoting cognitive dysfunctions in MS animals.

PMID:34727391 | DOI:10.1002/jdn.10155

J Orthop Res. 2021 Nov 2. doi: 10.1002/jor.25198. Online ahead of print.

ABSTRACT

Anterior cruciate ligament (ACL) injuries are increasingly common in adolescents, and injuries in this age-group are associated with many unique challenges. Recent large animal studies suggest that the size and function of the major bundles of the ACL change differently throughout skeletal growth. To better aid clinical treatment of pediatric partial ACL tears and better predict outcomes from age-specific treatments, there is a need to measure changes in ACL bundle size in humans during growth. As such, the objective of this study was to compare changes in the length and cross-sectional area (CSA) of the ACL and its primary bundles in adolescent human subjects. Magnetic resonance imaging (MRI) scans were analyzed to determine the visibility and integrity of the ACL and its anteromedial and posterolateral bundles. MRI scans were considered from a retrospective database of subjects ranging from 10 to 18 years of age. The ACL and its anteromedial and posterolateral bundles were segmented and reconstructed into 3D models, and length and CSA were calculated. Total ACL length and CSA were greater in males compared with females, with a statistically significant interaction between age and sex for CSA. Sex had a significant effect on the CSA of both bundles. These sex-dependent differences emerge with moderate to large effect sizes (range: d = 0.50 to d = 1.23) beginning around 13 years of age. Along with ACL bundle structure-function relationships previously established in preclinical animal models, these findings may point toward biomechanical changes in the adolescent human ACL.

PMID:34727387 | DOI:10.1002/jor.25198

J Periodontol. 2021 Nov 2. doi: 10.1002/JPER.21-0411. Online ahead of print.

ABSTRACT

BACKGROUND: In Grade C periodontitis in young patients (PerioC-Y), the functional roles of the subgingival community after years of periodontal treatment are still underexplored. This study evaluated the taxonomic and predicted functional content of the subgingival microbiome of PerioC-Y patients under supportive periodontal therapy (SPT).

METHODS: Clinical and microbiological data from subgingival biofilm were assessed from 10 PerioC-Y patients at two time points: at baseline and after 5.7±1.3 years of SPT. This was compared to 15 patients without a history of periodontitis. The V1-V3 and V4-V5 regions of the 16S rRNA were sequenced using the Illumina Miseq. Microbial composition was evaluated by the core microbiome, and alpha- and beta-diversity. The microbiome functional content was predicted using Picrust2, and the gene differential abundance was analyzed with DESeq2.

RESULTS: Clinical improvements were seen in PerioC-Y-SPT. Differences in β-diversity between PerioC-Y and Health were observed (Health x PerioC-Y-baseline, p = 0.02; Health x PerioC-Y-SPT, p = 0.05). Moreover, although β-diversity did not statistically change between baseline and SPT in PerioC-Y, the microbial correlation evidenced increased Streptococcus and decreased Treponema network contributions during SPT. Based on predicted functional data, treatment induced a reduction in genes related to flagellar protein and signal transduction in PerioC-Y. However, compared to healthy individuals, some genes remained more highly abundant in PerioC-Y-SPT, such as quorum sensing and efflux pump transporters.

CONCLUSION: Despite clinical improvements and a shift in taxonomic composition, the PerioC-Y patients’ periodontal treatment was not enough to reach a similar microbiome to patients without disease experience. Some functional content in this biofilm remained altered in PerioC-Y regardless of disease control. This article is protected by copyright. All rights reserved.

PMID:34727386 | DOI:10.1002/JPER.21-0411

Diabetes Ther. 2021 Nov 2. doi: 10.1007/s13300-021-01173-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Empagliflozin has demonstrated lower rates of cardiovascular outcomes vs. standard of care among patients with type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). However, the impact of empagliflozin compared to other branded antihyperglycemic agents (AHAs) on total cost of care has yet to be quantified.

METHODS AND RESULTS: This retrospective cohort study evaluated the impact of empagliflozin (n = 441) on costs and healthcare resource utilization (HCRU) vs. other branded AHAs (n = 13,122) among patients with T2DM and CVD, using the IQVIA PharMetrics^® Plus Claims Database (1 August 2013-31 December 2017). Date of the first prescription (index date) for empagliflozin or other branded AHAs was used to classify patients into study cohorts. All-cause costs and HCRU were computed on a per patient per month (PPPM) basis and compared across study cohorts using outcome-appropriate statistical models. Overall, the empagliflozin cohort was younger and had a lower comorbidity burden. After covariate adjustment, the total all-cause costs (mean difference – $412 PPPM; 95% CI – $593, – $214) were significantly lower for the empagliflozin cohort. These cost differences were mainly driven by lower all-cause medical costs (mean difference – $400 PPPM; 95% CI – $577, – $196). For HCRU, the mean adjusted all-cause visits in the physician office and other outpatient settings were lower with empagliflozin vs. other branded AHAs (p < 0.001).

CONCLUSIONS: This study demonstrated that the all-cause healthcare costs and HCRU were significantly lower for patients with T2DM and CVD who initiated empagliflozin vs. other branded AHAs. Along with the positive clinical evidence base of empagliflozin, these results can guide healthcare decision makers during therapy selection.

PMID:34727356 | DOI:10.1007/s13300-021-01173-0

Ophthalmol Ther. 2021 Nov 2. doi: 10.1007/s40123-021-00402-w. Online ahead of print.

ABSTRACT

INTRODUCTION: The aim of this study was to investigate the association of the HtrA1 rs11200638 polymorphism with neovascular age-related macular degeneration (nAMD) in Indonesia.

METHODS: This case-control study included 80 patients with nAMD and 85 controls. Demographic parameters and whole blood were collected from each participant. Genomic DNA was extracted and used to assess the rs11200638 genotype by PCR and restriction enzyme digestion. Associations between the HtrA1 rs11200638 polymorphism and other risk factors for susceptibility to nAMD were assessed using the logistic regression model.

RESULTS: Significant allelic associations between the HtrA1 polymorphism and nAMD were detected (odds ratio [OR] 8.67; 95% confidence interval [CI] 4.88-15.41; P < 0.001). Genotype analysis showed a statistical difference between the nAMD group and the control group (P < 0.001). In the multiple adjusted logistic regression model, people with the AA genotype were more likely to have nAMD although there was a wide confidence interval (OR 19.65; 95% CI 4.52-85.38; P < 0.001).

CONCLUSION: Our findings show that the risk of nAMD increased in the presence of risk alleles of HtrA1 rs11200638.

PMID:34727349 | DOI:10.1007/s40123-021-00402-w

Neurol Ther. 2021 Nov 2. doi: 10.1007/s40120-021-00296-7. Online ahead of print.

ABSTRACT

INTRODUCTION: C1q tumor necrosis factor (TNF)-related protein 9 (CTRP9) is a novel member of the C1q/TNF superfamily. According to our previous review, CTRP9 plays a vital role in the process of cardiovascular diseases, including regulating energy metabolism, modulating vasomotion, protecting endothelial cells, inhibiting platelet activation, inhibiting pathological vascular remodeling, stabilizing atherosclerotic plaques, and protecting the heart. We proposed that CTRP9 could play multiple positive and beneficial roles in vascular lesions in ischemic stroke (IS). Here, we aimed to study the relationship between serum CTRP9 and the etiology, severity, and prognosis of IS patients.

METHODS: A total of 302 patients with IS and 173 non-stroke controls were selected from the same hospital, and all patients with IS were followed up 12 months after stroke onset. Stroke etiology was classified according to the Trial of ORG 10172 in Acute Stroke Treatment classification. Symptomatic severity was determined using the National Institutes of Health Stroke Scale score. The lesion volume of acute cerebral ischemia was measured using magnetic resonance imaging (MRI). The unfavorable functional outcome was a combination of death or major disability 12 months after stroke onset. Receiver operating characteristic (ROC) curves and integrated discrimination improvement (IDI) and net reclassification improvement (NRI) statistics were applied in the statistical analysis.

RESULTS: We found that serum CTRP9 levels and the ratios of CTRP9/total cholesterol (TC), CTRP9/triglyceride (TG), CTRP9/low-density lipoprotein cholesterol (LDL-C), and CTRP9/high-density lipoprotein cholesterol (HDL-C) were associated with the presence of IS. Moreover, the serum CTRP9 concentration was positively associated with the severity of IS. Incorporation of CTRP9/LDL-C levels into a fully adjusted model for IS-cardioembolic (CE) improved discrimination and calibration, and significantly improved reclassification. In addition, CTRP9 was a predictor of unfavorable functional outcomes.

CONCLUSIONS: All the findings indicated that serum CTRP9 could be a promising blood-derived biomarker for the early evaluation and prognosis assessment of IS.

TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800020330.

PMID:34727346 | DOI:10.1007/s40120-021-00296-7

Int J Comput Assist Radiol Surg. 2021 Nov 2. doi: 10.1007/s11548-021-02522-x. Online ahead of print.

ABSTRACT

PURPOSE: The amount of ultrasound (US) breast examinations continues to grow rapidly because of the wider endorsement of breast cancer screening programs. Cysts are the most commonly diagnosed breast lesions. Atypical breast cysts can be a serious differentiation problem in the US. Our goal was to develop noninvasive automated US grayscale image analysis for the cystic and solid breast lesion differentiation based on mathematical image post-processing.

MATERIALS AND METHODS: We used a set of 217 ultrasound images of proven 107 cystic (including 53 atypical) and 110 solid lesions. Empirical statistical and morphological models of the lesions were used to obtain features. The AUC indicator and Student’s t test were used to assess the quality of the individual features. The Pearson correlation matrix was used to calculate the correlation between various features. The LASSO and stepwise regression methods were used to determine the most significant features. Finally, the lesion classification was carried out by the various methods.

RESULTS: The use of LASSO regression for the feature selection made it possible to select the most significant features for classification. The sensitivity increased from 87.1% to 89.2% and the specificity-from 92.2 to 94.8%. After the correlation matrix construction, it was found that features with a high value of the correlation coefficient (0.72; 0.75) can also be used to improve the quality of the classification.

CONCLUSION: The construction of the empirical model of the lesion pixels brightness behavior can provide parameters that are important for the correct classification of ultrasound images. The optimal set of features with the maximum discriminant characteristics may not be consistent with the correlation of features and the value of the AUC index. Features with a low AUC index (in our case 0.72) can also be important for improving the quality of the classification.

PMID:34727337 | DOI:10.1007/s11548-021-02522-x

Mol Biol Rep. 2021 Nov 2. doi: 10.1007/s11033-021-06910-z. Online ahead of print.

ABSTRACT

BACKGROUND: Signal recognition particle (SRP) promotes co-translational translocation of the proteins through or into the endoplasmic reticulum membrane and it also has elongation arrest function. SRP9 is one of the six protein subunits of SRP and functions in elongation arrest activity by forming a heterodimeric structure with SRP14. It is one of the substrates of ADAR, which has been found to have a role in breast cancer. This study was conducted to investigate the SRP9 protein expression in normal and tumor tissues of patients with breast cancer and determine its prognostic significance.

METHODS AND RESULTS: A total of 32 female patients who were diagnosed as having primary breast cancer and underwent surgery were included in the study. Western Blotting was performed to detect SRP9 protein expression levels in normal and tumor tissue samples. Clinical and pathologic characteristics were analyzed to assess the prognostic significance. SRP9 protein expression was statistically higher in the breast cancer tissue samples compared to normal matched tissue, and the mean SRP9 protein expression levels of breast cancer tissue normal tissue samples were 1.019 ± 1.011 and 0.551 ± 0.456, respectively (p = 0.001). SRP9 protein expression levels in tumor tissue of patients with lymph node metastasis, tumor size > 2 cm, estrogen receptor-positive, progesterone receptor-positive, and HER-2 negative were statistically higher than in normal tissue (p < 0.05).

CONCLUSIONS: It is vital to clarify the roles of molecules such as SRP9 in understanding the pathogenesis of breast cancer. In our study, we showed that SRP9 expression increased in breast cancer and was associated with disease-related parameters.

PMID:34727289 | DOI:10.1007/s11033-021-06910-z

Carbon Balance Manag. 2021 Nov 2;16(1):34. doi: 10.1186/s13021-021-00196-1.

ABSTRACT

BACKGROUND: Allometric equations are used to estimate biomass and carbon stock of forests. In Ethiopia, despite the presence of large floral diversity, only a few site-specific allometric equations have been developed so far. This study was conducted in the Omo-Gibe woodland of south-western Ethiopia to develop an allometric equation to estimate the Above-ground Biomass (AGB) of the four Acacia species (Senegalia polyacantha, Vachellia seyal, Vachellia etbaica and Vachellia tortilis). Fifty-four (54) Acacia trees were sampled and measured within 35 temporarily established square plots. In each plot, dendrometric variables were measured to derive the models based on combinations of Diameter at Breast Height (DBH), height, and wood density as predictor variables. Model performance was evaluated using goodness-of-fit statistics. The biomass was compared using four allometric biomass models that have been widely used in the tropics.

RESULTS: The model containing DBH alone was more accurate to estimate AGB compared to the use of multiple predictor variables. This study, therefore, substantiated the importance of site-specific allometric equations in estimating the AGB of Acacia woodlands. This is because a site-specific allometric equation recognizes the environmental factors, vegetation types and management practices.

CONCLUSIONS: The results of this study contribute to a better understanding of allometric equations and an accurate estimate of AGB of Acacia woodlands in Ethiopia and similar ecosystems elsewhere.

PMID:34727268 | DOI:10.1186/s13021-021-00196-1