Nevin Manimala

J Crohns Colitis. 2022 Sep 10:jjac132. doi: 10.1093/ecco-jcc/jjac132. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The number of prospective population-based studies on Crohn’s disease(CD) is still limited from Eastern Europe. The present study is a continuation of the Veszprem IBD cohort. Our aim was to analyze incidence, prevalence, disease phenotype, treatment strategy, disease course and surgical outcomes in a prospective population-based inception cohort including CD patients diagnosed between 2007 and 2018.

METHODS: 421 consecutive inception patients were included (male/female:237/184; mean age at diagnosis: 33.3±16.2years). Both in-hospital and outpatient records were collected and comprehensively reviewed. Demographic data was derived from the Hungarian Central Statistical Office.

RESULTS: Mean incidence rate was 9.9 (CI95%: 9.0-10.9)/10 5 person-years in this 12-year period. Prevalence rate was 236.8 (CI95%: 220.8-252.8) in 2015. 17.6% and 20.0% of the patients had stenosing(B2) and penetrating(B3) disease behavior at diagnosis. The probability of disease behavior progression from luminal to B2/B3 phenotype was 14.7%(SE:2.2) at 5 years after diagnosis. Distribution of maximal therapeutic steps during the total follow-up (8.5y, SD:3.3) were 5-ASA in 15.7%, corticosteroids in 14.3%, immunosuppressives in 42.5% and biologic therapy in 26.2%. The probability of receiving biological therapy after diagnosis was 20.9%(SE:2.0) at 5 years. The probability of first resective surgery was 20.7%(SE:2.0) at 1 year, 26.1%(SE:2.2) at 5 years and 30.7%(SE:2.4) at 10 years, while perianal surgery rate was 31.3% among patients with perianal involvement.

CONCLUSIONS: The incidence of CD in Hungary was high, similar to high-incidence areas in Western Europe. Treatment strategies are reflecting the biological era. Disease behavior progression was lower, as well as long-term (10y) surgery rates decreased compared to data from previous decades.

PMID:36087109 | DOI:10.1093/ecco-jcc/jjac132

Physiol Plant. 2022 Sep 10:e13779. doi: 10.1111/ppl.13779. Online ahead of print.

ABSTRACT

The current study was performed under controlled conditions to study the effects of exogenous potassium application on carotenoid contents and drought tolerance in Camelina. Water deficit levels such as 100% FC (control) and 40% FC (drought stress) were imposed after germination of Camelina plants grown to maturity, and different treatments of exogenous K+ were applied at the vegetative stage. We have reported seventeen traits of plant growth, physiology, antioxidant enzyme activity, focusing on carotenoids in Camelina to explore their potential yield and yield components. For this purpose, we used multivariate analysis techniques (descriptive statistics, correlation matrix, analysis of variance (ANOVA) and principal components analysis (PCA) to determine the best relation between potassium and studied traits. The results showed a large number of variations in the studied trait under control and water deficit condition. Plant fresh weight (g) was negatively correlated with shoot length and SOD insignificantly correlated with plant fresh weight (g) under water deficit conditions. Potassium loading predicted that foliar application (3mM K2SO4), foliar application (6mM KNO3), foliar application (12mM KNO3) and foliar application (12mM K2SO4) are the important doses that contribute the most to enhance the growth, physiological and biochemical activities and carotenoids to improve the Camelina yield under water deficit condition. These doses should be considered in the future to improve the Camelina yield under semi-arid conditions with increased genetic diversity (varietal selection). This article is protected by copyright. All rights reserved.

PMID:36087099 | DOI:10.1111/ppl.13779

Hum Brain Mapp. 2022 Sep 10. doi: 10.1002/hbm.26068. Online ahead of print.

ABSTRACT

We aim to synthesize brain time-of-flight (TOF) PET images/sinograms from their corresponding non-TOF information in the image space (IS) and sinogram space (SS) to increase the signal-to-noise ratio (SNR) and contrast of abnormalities, and decrease the bias in tracer uptake quantification. One hundred forty clinical brain ¹⁸ F-FDG PET/CT scans were collected to generate TOF and non-TOF sinograms. The TOF sinograms were split into seven time bins (0, ±1, ±2, ±3). The predicted TOF sinogram was reconstructed and the performance of both models (IS and SS) compared with reference TOF and non-TOF. Wide-ranging quantitative and statistical analysis metrics, including structural similarity index metric (SSIM), root mean square error (RMSE), as well as 28 radiomic features for 83 brain regions were extracted to evaluate the performance of the CycleGAN model. SSIM and RMSE of 0.99 ± 0.03, 0.98 ± 0.02 and 0.12 ± 0.09, 0.16 ± 0.04 were achieved for the generated TOF-PET images in IS and SS, respectively. They were 0.97 ± 0.03 and 0.22 ± 0.12, respectively, for non-TOF-PET images. The Bland & Altman analysis revealed that the lowest tracer uptake value bias (-0.02%) and minimum variance (95% CI: -0.17%, +0.21%) were achieved for TOF-PET images generated in IS. For malignant lesions, the contrast in the test dataset was enhanced from 3.22 ± 2.51 for non-TOF to 3.34 ± 0.41 and 3.65 ± 3.10 for TOF PET in SS and IS, respectively. The implemented CycleGAN is capable of generating TOF from non-TOF PET images to achieve better image quality.

PMID:36087092 | DOI:10.1002/hbm.26068

Am J Hematol. 2022 Sep 10. doi: 10.1002/ajh.26724. Online ahead of print.

ABSTRACT

RUNX1-mutated (mRUNX1) acute myeloid leukemia (AML) has historically been associated with poor outcomes in the setting of conventional chemotherapy. The prognostic impact of mRUNX1 AML is not well-established in the current era of lower-intensity treatment regimens incorporating venetoclax. We retrospectively analyzed 907 patients with newly diagnosed AML, including 137 patients with mRUNX1 AML, who underwent first-line therapy with intensive chemotherapy (IC), low-intensity therapy without venetoclax (LIT without VEN), or LIT with VEN. When stratified by RUNX1 status, there was no statistically significant difference in outcomes between mRUNX1 and wild type (wtRUNX1) AML, regardless of therapy received. However, among patients who received LIT with VEN, there was a trend towards superior overall survival (OS) in those with mRUNX1 AML (median OS for mRUNX1 vs wtRUNX1: 25.1 vs 11.3 months; 2-year OS 54% vs 33%; P=0.12). In patients without another adverse-risk cyto-molecular feature, the presence of mRUNX1 conferred inferior OS in patients who received IC (P=0.02) or LIT without VEN (P=0.003) but not in those who received LIT with VEN (mRUNX1 vs wtRUNX1: 25.1 vs 30.0 months; 2-year OS 59% vs 54%; P=0.86). A multivariate analysis showed possible interaction between RUNX1 mutation status and treatment, suggesting a differential prognostic impact of RUNX1 mutations when patients received IC versus LIT with VEN. In summary, the prognostic impact of mRUNX1 AML may be treatment-dependent, and the presence of RUNX1 mutations may not impact clinical outcomes when venetoclax-based regimens are used. This article is protected by copyright. All rights reserved.

PMID:36087091 | DOI:10.1002/ajh.26724

Clin Exp Ophthalmol. 2022 Sep 10. doi: 10.1111/ceo.14167. Online ahead of print.

ABSTRACT

BACKGROUND: To explore the use of a thermoreversible copolymer gel coating to prevent donor tissue scrolling in Descemet’s membrane endothelial keratoplasty (DMEK).

METHODS: PLGA-PEG-PLGA triblock copolymer was synthesised via ring opening polymerisation. Two formulations were fabricated and gelation properties characterized using rheological analyses. Endothelial cytotoxicity of the copolymer was assessed using a Trypan Blue exclusion assay. Thickness of the copolymer gel coating on the endothelial surface was analysed using anterior segment optical coherence tomography (OCT) (RTVue-100, Optovue Inc., California, USA). Gold nanoparticles were added to the copolymer to aid visualization using OCT. Prevention of Descemet membrane donor scrolling was represented via a novel, in vitro, immersion of copolymer coated donor graft material.

RESULTS: Two different formulations of PLGA-PEG-PLGA copolymer were successfully fabricated and the desired peak gelling temperature of 24°C was achieved by polymer blending. Application of 20%, 30% and 40% (w/v) polymer concentrations resulted in a statistically significant increase in polymer thickness on the endothelium (p<0.001). There was no detectable endothelial cytotoxicity. The polymer was easy to apply to the endothelium and prevented scrolling of the DMEK graft.

CONCLUSION: This PLGA-PEG-PLGA thermoreversible copolymer gel could be exploited as a therapeutic aid for preventing DMEK graft scrolling.

PMID:36086942 | DOI:10.1111/ceo.14167

J Cosmet Dermatol. 2022 Sep 10. doi: 10.1111/jocd.15375. Online ahead of print.

ABSTRACT

BACKGROUND: Subcision method is one of the main techniques for treatment of acne scars or Stromal-Vascular Fraction (SVF) and combined therapy can improve treatment strategy.

OBJECTIVE: To use subcision method along with SVF for treatment of acne scar and comprised with alone subcision method.

MATERIALS AND METHODS: In this double-blind clinical trial study, ten patients with acne scars were entered into the study. Subcision technique was randomly performed on one side of the face and subcision technique plus SVF on opposite side of the face. All patients were examined before treatment and after three months by Visioface for volume, area, and depth of scars, as well as thickness and density of the epidermis and dermis of the scars in question. In addition, doctor’s and patients’ satisfaction, tolerability, and safety were determined after three months of treatment. Finally, statistical analysis was done by SPPS, version 25.

RESULTS: In terms of volume and area of scars, the mean percent change were 46.55± 13.92 and 44.60± 5.76, for the case group, and 13.31± 9.27 and 11.28± 9.64 for the control group, respectively. So combined therapy led to significant recovery compared with alone subcision method (p value<0.001). In both interventions, increase of density and thickness was proven after treatment, alsoa significant difference in complete, epidermal, and dermal thickness and epidermal density variables was observed between combined therapy and alone subcision (p value< 0.05). Mean score of doctor’s and patients’ satisfaction in combined therapy (7.10± 0.74 and 7.10± 0.99, respectively) was also significantly higher than subcision alone (5.50± 0.53 and 5.30± 1.25, respectively). Finally, No complications were observed in the patients.

CONCLUSION: According to acquired results, combined therapy can be considered as effective and safe treatment for acne scars with significant higher efficacy compared with subcision alone.

PMID:36086927 | DOI:10.1111/jocd.15375

Eur J Neurol. 2022 Sep 10. doi: 10.1111/ene.15549. Online ahead of print.

ABSTRACT

BACKGROUND: Circulating metabolites have been implicated in stroke pathogenesis, but their genetic determinants is understudied. Using Mendelian randomization approach, we aim to provide evidence for the relationship of circulating metabolites on risk of stroke and its subtypes.

METHODS: Genetic instruments of 102 circulating metabolites were obtained from a genome-wide association study (GWAS), including 24,925 European individuals. Stroke were extracted from MEGASTROKE dataset (67,162 cases; 454,450 controls) and lacunar stroke dataset (7338 cases; 254,798 controls). The magnetic resonance imaging (MRI) markers of cerebral small vessel diseases (CSVD) and microstructural injury were evaluated by GWAS of white matter hyperintensities (N=18,381), fractional anisotropy (N=17,663), mean diffusivity (N=17,467) and brain microbleeds (N=25,862). The inverse-variance weighted method Mendelian randomization was used as primary analytical method, and directional pleiotropy and heterogeneity were examined in sensitivity analyses.

RESULTS: Genetic predisposition to higher level of cholesterol in small and low-density lipoprotein (LDL) were associated with risk of stroke (OR[95%CI]=1.14[1.08-1.21], p=5.98*10^-7 ), especially for large-artery atherosclerotic stroke (OR[95%CI]=1.34[1.19-1.52], p=1.90*10^-6 ). Total lipids in LDL particles were also associated with risk of stroke. Genetically determined higher cholesterol level in high-density lipoprotein (HDL-C) was associated with risk of intracerebral hemorrhage (OR[95%CI]=1.74[1.23-2.45], p=1.66*10^-3 ). No statistically significant association was found between genetic predisposition to circulating metabolites and MRI markers of CSVD and microstructural injury.

CONCLUSIONS: Genetically determined levels of lipids in small LDL were associated with the risk of stroke, suggesting a therapeutic strategy targeting small LDL levels may be crucial for stroke prevention. HDL-C was positively associated with the risk of intracerebral hemorrhage.

PMID:36086915 | DOI:10.1111/ene.15549

Photochem Photobiol. 2022 Sep 10. doi: 10.1111/php.13711. Online ahead of print.

ABSTRACT

Gingival fibroblasts have critical roles in oral wound healing. Photobiomodulation (PBM) has been shown to promote mucosal healing and is now recommended for managing oncotherapy-associated oral mucositis. This study examined the effects of the emission mode of a 940 nm diode laser on the viability and migration of human gingival fibroblasts. Cells were cultured in a routine growth media and treated with PBM (average power 0.1 W/cm² , average fluence 3 J/cm² , every 12h for 6 sessions) in one continuous wave (CW) and two pulsing settings with 20 % and 50 % duty cycles. Cell viability was assessed using MTT, and digital imaging quantified cell migration. After 48 and 72 hours, all treatment groups had significantly higher viability (n = 6, p < 0.05) compared to the control. The highest viability was seen in the pulsed (20% duty cycle) group at the 72-hour time point. PBM improved fibroblast migration in all PBM-treated groups, but differences were not statistically significant (n = 2, p > 0.05). PBM treatments can promote cell viability in both continuous and pulsed modes. Further studies are needed to elucidate the optimal setting for PBM-evoked responses for its rationalized use in promoting specific phases of oral wound healing.

PMID:36086909 | DOI:10.1111/php.13711

J Physiol. 2022 Sep 10. doi: 10.1113/JP282758. Online ahead of print.

ABSTRACT

Naturally log-scaled quantities abound in the nervous system. Distributions of these quantities have nonintuitive properties, which have implications for data analysis and understanding of neural circuits. Here we review the log-scaled statistics of neuronal spiking and the relevant analytical probability distributions. Recent work using log-scaling revealed that inter-spike intervals of forebrain neurons segregate into discrete modes that reflect spiking at different timescales and are each well-approximated by a gamma distribution. Each neuron spends most of the time in an irregular spiking ‘ground state’ with the longest intervals, which determines the mean firing rate of the neuron. Across the entire neuronal population, firing rates are log-scaled and well approximated by the gamma distribution, with a small number of highly active neurons and an overabundance of low rate neurons (the ‘dark matter’). These results are intricately linked to a heterogeneous balanced operating regime, which confers upon neuronal circuits multiple computational advantages and has evolutionarily ancient origins. This article is protected by copyright. All rights reserved.

PMID:36086892 | DOI:10.1113/JP282758

Cell Transplant. 2022 Jan-Dec;31:9636897221120434. doi: 10.1177/09636897221120434.

ABSTRACT

Congenital heart diseases, including single ventricle circulations, are clinically challenging due to chronic pressure overload and the inability of the myocardium to compensate for lifelong physiological demands. To determine the clinical relevance of autologous umbilical cord blood-derived mononuclear cells (UCB-MNCs) as a therapy to augment cardiac adaptation following surgical management of congenital heart disease, a validated model system of right ventricular pressure overload due to pulmonary artery banding (PAB) in juvenile pigs has been employed. PAB in a juvenile porcine model and intramyocardial delivery of UCB-MNCs was evaluated in three distinct 12-week studies utilizing serial cardiac imaging and end-of-study pathology evaluations. PAB reproducibly induced pressure overload leading to chronic right ventricular remodeling including significant myocardial fibrosis and elevation of heart failure biomarkers. High-dose UCB-MNCs (3 million/kg) delivered into the right ventricular myocardium did not cause any detectable safety issues in the context of arrhythmias or abnormal cardiac physiology. In addition, this high-dose treatment compared with placebo controls demonstrated that UCB-MNCs promoted a significant increase in Ki-67-positive cardiomyocytes coupled with an increase in the number of CD31+ endothelium. Furthermore, the incorporation of BrdU-labeled cells within the myocardium confirmed the biological potency of the high-dose UCB-MNC treatment. Finally, the cell-based treatment augmented the physiological adaptation compared with controls with a trend toward increased right ventricular mass within the 12 weeks of the follow-up period. Despite these adaptations, functional changes as measured by echocardiography and magnetic resonance imaging did not demonstrate differences between cohorts in this surgical model system. Therefore, this randomized, double-blinded, placebo-controlled pre-clinical trial establishes the safety of UCB-MNCs delivered via intramyocardial injections in a dysfunctional right ventricle and validates the induction of cardiac proliferation and angiogenesis as transient paracrine mechanisms that may be important to optimize long-term outcomes for surgically repaired congenital heart diseases.

PMID:36086821 | DOI:10.1177/09636897221120434