Tag: nevin manimala

Parasitol Res. 2022 Oct 4. doi: 10.1007/s00436-022-07679-1. Online ahead of print.

ABSTRACT

Liver flukes, Fasciola spp., are veterinary and medically important parasites infecting numerous species of economically important animals in addition to humans on a global scale. The components of transforming growth factor beta (TGF-β) signalling are widely distributed throughout the animal kingdom and are considerably conserved. Through shared common signal transduction mechanisms, crosstalk of TGF-β signalling between a host and the parasite during infection is possible. Herein, we have identified and undertaken the molecular characterisation of a putative TGF-β homologue from the tropical liver fluke F. gigantica (FgTLM). A FgTLM cDNA was 3557 bp in length, it encoded for 620 amino acid polypeptide which consisted of 494 amino acids of prodomain and 126 amino acids comprising the mature protein. FgTLM displayed characteristic structures of mammalian TGF-β ligands that were unique to the inhibin-β chain, monomer of activin. A phylogenetic analysis revealed the high degree of conservation with TGF-β molecules from trematode species. Interestingly, the sequence of amino acid in the active domain of FgTLM was completely identical to FhTLM from F. hepatica. FgTLM expressed throughout the lifecycle of F. gigantica but was highly expressed in developmental active stages. The dynamics of expression of FgTLM during the developmental stages of F. gigantica was comparable to the pattern of TGF-β expression in F. hepatica. Our findings demonstrated that FgTLM exhibits a high level of similarity to FhTLM in the context of both amino acid sequence and the life stage expression patterns. These similarities underline the possibility that the FgTLM molecule might have the same properties and functions as FhTLM in biological processes of the immature parasites and host immune evasion. Consequently, the specific biological functions of FgTLM on either parasite or relevant hosts need to be defined experimentally.

PMID:36194274 | DOI:10.1007/s00436-022-07679-1

Diabetologia. 2022 Oct 4. doi: 10.1007/s00125-022-05805-3. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: We previously detected indications that beta cell function is protected by gluten-free diet (GFD) introduced shortly after the onset of childhood type 1 diabetes. The present aim was to assess whether GFD was associated with changes in the gut bacteriome composition and in its functional capacity, and whether such changes mediated the observed effects of GFD on beta cell function.

METHODS: Forty-five children (aged 10.2 ± 3.3 years) were recruited into a self-selected intervention trial primarily focused on determining the role of GFD on beta cell preservation ( ClinicalTrials.gov NCT02867436). Stool samples were collected prior to the dietary intervention and then at 3-month intervals. A total of 128 samples from the GFD group and 112 from the control group were analysed for bacteriome 16S rDNA community profiles, the bacteriome functional capacity was predicted using PICRUSt2 and actual gut metabolome profiles measured using NMR. Intestinal permeability was assessed using serum zonulin concentrations at 1, 6 and 12 months and lactulose/mannitol tests at the end of intervention. Dietary questionnaires were used to ensure that the dietary intervention did not result in differences in energy or nutrient intake.

RESULTS: The bacteriome community composition changed during the intervention with GFD: of abundant genera, a 3.3-fold decrease was noted for Bifidobacterium genus (adjusted p=1.4 × 10^-4 in a DESeq2 model, p=0.026 in generalised estimating equations model), whereas a 2.4-fold increase was observed in Roseburia (adjusted p=0.02 in DESeq2 model, p=0.002 in generalised estimating equations model). The within-sample (alpha) diversity did not change, and there was no statistically significant clustering of GFD samples in the ordination graphs of beta diversity. Neither of the genera changes upon GFD intervention showed any association with the pace of beta cell loss (p>0.50), but of the remaining taxa, several genera of Bacteroidaceae family yielded suggestive signals. The faecal metabolome profile ordination correlated with that of bacteriomes but did not associate with GFD or categories of beta cell preservation. There was no indication of changes in gut permeability.

CONCLUSIONS/INTERPRETATION: The bacteriome reacted to GFD, but the changes were unrelated to the pace of beta cell capacity loss. The previously observed moderately protective effect of GFD is therefore mediated through other pathways.

PMID:36194251 | DOI:10.1007/s00125-022-05805-3

Diabetologia. 2022 Oct 4. doi: 10.1007/s00125-022-05801-7. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: Genetic predisposition to type 2 diabetes is well-established, and genetic risk scores (GRS) have been developed that capture heritable liabilities for type 2 diabetes phenotypes. However, the proteins through which these genetic variants influence risk have not been thoroughly investigated. This study aimed to identify proteins and pathways through which type 2 diabetes risk variants may influence pathophysiology.

METHODS: Using a proteomics data-driven approach in a discovery sample of 7241 White participants in the Atherosclerosis Risk in Communities Study (ARIC) cohort and a replication sample of 1674 Black ARIC participants, we interrogated plasma levels of 4870 proteins and four GRS of specific type 2 diabetes phenotypes related to beta cell function, insulin resistance, lipodystrophy, BMI/blood lipid abnormalities and a composite score of all variants combined.

RESULTS: Twenty-two plasma proteins were identified in White participants after Bonferroni correction. Of the 22 protein-GRS associations that were statistically significant, 10 were replicated in Black participants and all but one were directionally consistent. In a secondary analysis, 18 of the 22 proteins were found to be associated with prevalent type 2 diabetes and ten proteins were associated with incident type 2 diabetes. Two-sample Mendelian randomisation indicated that complement C2 may be causally related to greater type 2 diabetes risk (inverse variance weighted estimate: OR 1.65 per SD; p=7.0 × 10^-3), while neuropilin-2 was inversely associated (OR 0.44 per SD; p=8.0 × 10^-3).

CONCLUSIONS/INTERPRETATION: Identified proteins may represent viable intervention or pharmacological targets to prevent, reverse or slow type 2 diabetes progression, and further research is needed to pursue these targets.

PMID:36194249 | DOI:10.1007/s00125-022-05801-7

ACS Macro Lett. 2022 Oct 4:1217-1223. doi: 10.1021/acsmacrolett.2c00517. Online ahead of print.

ABSTRACT

Poly(methyl methacrylate/n-butyl acrylate) [P(MMA/BA)] copolymer with an alternating structure was synthesized via an activator regenerated by electron transfer (ARGET) atom transfer radical (co)polymerization (ATRP) of 2-ethylfenchyl methacrylate (EFMA) and n-butyl acrylate (BA) with subsequent postpolymerization modifications (PPM). Due to the steric hindrance of the bulky pendant group of EFMA, as well as the low reactivity ratio of BA in copolymerization with methacrylates, copolymerization of EFMA and BA generated a copolymer with a high content of alternating dyads. A subsequent PPM procedure of the alternating EFMA/BA copolymer was comprised of the hydrolysis of a tertiary ester by trifluoroacetic acid and methylation by (trimethylsilyl)diazomethane. After the modifications, the architecture of the obtained alternating MMA/BA copolymers was compared with gradient and statistical copolymers with overall similar compositions, molecular weights, and dispersities. ¹³C NMR indicated the absence of either MMA/MMA/MMA or BA/BA/BA sequences, in contrast to an abundance of homotriads in either the statistical or especially in the gradient copolymer. All three copolymers had similar glass transition temperatures, as measured by differential scanning calorimetry (DSC), but the alternating copolymer had the narrowest range of glass transition.

PMID:36194204 | DOI:10.1021/acsmacrolett.2c00517

J Chin Med Assoc. 2022 Oct 4. doi: 10.1097/JCMA.0000000000000819. Online ahead of print.

ABSTRACT

BACKGROUND: Neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by total mesorectal excision has become the standard of care for advanced rectal cancer, but the most effective regimen of chemotherapeutic agents has not yet been determined. The purpose of this study is to determine the effect of Mitomycin-C (MMC) in nCCRT for rectal cancer.

METHODS: From 2000 to 2017, patients with rectal adenocarcinoma who received nCCRT followed by radical surgery were enrolled in our study. The patients were retrospectively separated into two groups according to nCCRT regimens (with or without MMC). Other factors related to cancer downstaging after nCCRT, disease-free survival (DFS) and overall survival (OS)were analyzed.

RESULTS: One hundred ninety-five patients received radiotherapy (RT) + MMC + oral tegafur-uracil (UFUR), and 191 patients received RT + UFUR without MMC as neoadjuvant CCRT. Adding MMC might increase the downstaging rate (odds ratio (OR) = 1.520, p = 0.058), and downstaging had significant effect to improve overall survival (OR = 1.726, p = 0.002) and disease-free survival (OR = 2.185, p < 0.001). The overall survival and disease-free survival were improved in patients who received MMC, although this result did not reach a statistically significant difference. There was a higher incidence of low-grade toxicities in the MMC group, especially neutropenia, genitourinary side effects, and dermatological side effects (p < 0.001).

CONCLUSION: Adding MMC to the regimen of nCCRT for rectal adenocarcinoma is shown to increase tumor downstaging rate and improve disease-free and overall survival, although these benefits come at the cost of increased low-grade toxicities. Prospective randomized studies are needed to explore the role of MMC in nCCRT for rectal cancer.

PMID:36194168 | DOI:10.1097/JCMA.0000000000000819

J Chin Med Assoc. 2022 Oct 4. doi: 10.1097/JCMA.0000000000000818. Online ahead of print.

ABSTRACT

BACKGROUND: Iron is a vital trace element for energy production and oxygen transportation; importantly, it is essential to athletic performance. Maintaining iron balance is tightly controlled at systemic and cellular levels. This study aimed to determine serum iron tests, hepcidin levels, and cellular iron import and export activities in peripheral blood mononuclear cells (PBMCs) in ultramarathon runners to elucidate the association of systemic inflammation response and iron metabolism.

METHODS: Sixteen amateur runners were enrolled. Blood samples were taken one week before, immediate, and 24 h after the run. Plasma hepcidin levels were measured by enzyme-linked immunosorbent assay. The expression levels of divalent metal iron transporter 1 (DMT1), ZRT/IRT-like protein 14 (ZIP14), transferrin receptor 1 (TfR1), and ferroportin (FPN) in PBMCs were measured using real-time quantitative reverse-transcription polymerase chain reaction.

RESULTS: Serum iron concentrations and transferrin saturation significantly decreased immediately after the race and dramatically recovered 24 h post-race. Serum ferritin levels had a statistically significant rise immediately after the race and remained high 24 h after the completion of the race. Ultramarathons were associated with increased plasma interleukin (IL)-6 concentrations corresponding to the state of severe systemic inflammation and therefore boosted plasma hepcidin levels. The expression levels of DMT1 and FPN mRNA were markedly decreased immediately and 24 h after the race. The ZIP14 and TfR1 mRNA expression in PBMCs significantly decreased immediately after the race and returned to the baseline level at 24 h post-race. Positive significant correlations were observed between plasma hepcidin and ferritin levels.

CONCLUSION: Iron homeostasis and systemic inflammatory response are closely interconnected. Cellular iron import and export mRNA activities in PBMCs were acutely inhibited during an ultramarathon.

PMID:36194166 | DOI:10.1097/JCMA.0000000000000818

Radiology. 2022 Oct 4:213256. doi: 10.1148/radiol.213256. Online ahead of print.

ABSTRACT

Background MRI is a standard of care tool to measure liver iron concentration (LIC). Compared with regulatory-approved R2 MRI, R2* MRI has superior speed and is available in most MRI scanners; however, the cross-vendor reproducibility of R2*-based LIC estimation remains unknown. Purpose To evaluate the reproducibility of LIC via single-breath-hold R2* MRI at both 1.5 T and 3.0 T with use of a multicenter, multivendor study. Materials and Methods Four academic medical centers using MRI scanners from three different vendors (three 1.5-T scanners, one 2.89-T scanner, and two 3.0-T scanners) participated in this prospective cross-sectional study. Participants with known or suspected liver iron overload were recruited to undergo multiecho gradient-echo MRI for R2* mapping at 1.5 T and 3.0 T (2.89 T or 3.0 T) on the same day. R2* maps were reconstructed from the multiecho images and analyzed at a single center. Reference LIC measurements were obtained with a commercial R2 MRI method performed using standardized 1.5-T spin-echo imaging. R2*-versus-LIC calibrations were generated across centers and field strengths using linear regression and compared using F tests. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic performance of R2* MRI in the detection of clinically relevant LIC thresholds. Results A total of 207 participants (mean age, 38 years ± 20 [SD]; 117 male participants) were evaluated between March 2015 and September 2019. A linear relationship was confirmed between R2* and LIC. All calibrations within the same field strength were highly reproducible, showing no evidence of statistically significant center-specific differences (P > .43 across all comparisons). Calibrations for 1.5 T and 3.0 T were generated, as follows: for 1.5 T, LIC (in milligrams per gram [dry weight]) = -0.16 + 2.603 × 10^-2 R2* (in seconds^-1); for 2.89 T, LIC (in milligrams per gram) = -0.03 + 1.400 × 10^-2 R2* (in seconds^-1); for 3.0 T, LIC (in milligrams per gram) = -0.03 + 1.349 × 10^-2 R2* (in seconds^-1). Liver R2* had high diagnostic performance in the detection of clinically relevant LIC thresholds (area under the ROC curve, >0.98). Conclusion R2* MRI enabled accurate and reproducible quantification of liver iron overload over clinically relevant ranges of liver iron concentration (LIC). The data generated in this study provide the necessary calibrations for broad clinical dissemination of R2*-based LIC quantification. ClinicalTrials.gov registration no.: NCT02025543 © RSNA, 2022 Online supplemental material is available for this article.

PMID:36194113 | DOI:10.1148/radiol.213256

J Burn Care Res. 2022 Oct 4:irac144. doi: 10.1093/jbcr/irac144. Online ahead of print.

ABSTRACT

It is crucial to provide an adequate level of sedation and analgesia during burn dressing changes in the pediatric population due to the amount of pain and anxiety patients experience during the procedure. To evaluate the safety and efficacy of an intensivist-based deep sedation regimen using a combination of propofol and ketamine to provide procedural sedation to pediatric burn patients. This is a retrospective chart review of pediatric patients who underwent inpatient burn wound dressing changes from 2011 through 2021. Demographic and clinical data, including age, length of the procedure, recovery time, medications doses, and adverse events, were collected. A total of 104 patients aged between 45 and 135 months with a median total burn body surface area (TBSA) of 11.5 % (IQR 4.0, 25.0) underwent 378 procedural sedation encounters with propofol and ketamine-based sedation. The median total dose of propofol was 7 mg/kg (IRQ 5.3, 9.2). Of these sedations, 64 (17%) had minor adverse events, of which 50 (13%) were transient hypoxemia, 12 (3%) were upper airway obstruction, and 2 (0.5%) were hypotension. There were no serious adverse events. Hypoxemia was not related to age, weight, gender, burn TBSA, or total dose of propofol. There were 35 (33.6%) patients who had repetitive sedation encounters with no statistically significant changes in propofol dose or adverse events with the repeated encounters. Children can be effectively sedated for repetitive inpatient burn dressing changes. Given the high-risk patient populations, this procedure should be performed under the vigilance of highly trained providers.

PMID:36194090 | DOI:10.1093/jbcr/irac144

Eur J Transl Myol. 2022 Oct 4. doi: 10.4081/ejtm.2022.10736. Online ahead of print.

ABSTRACT

The endeavor to evaluate the linearity of myofibrillar structures and their potential deviation from a straight line is a fascinating problem in muscle tissue image analysis. In this Letter, we suggest two different strategies for solving the same challenge. The first strategy is based on an alignment index, which could be derived by comparing the sum of the lengths of the individual sarcomeres with the distance between the “head” of the first and the “tail” of the last sarcomere. The second strategy relies on circular statistics, which takes a cue from an already suggested method. Our proposed methods are alternatives: the former has the advantage of simplicity; the latter is certainly more elegant and gives greater substance to statistical analysis, but in contrast, it also has greater computational complexity.

PMID:36193819 | DOI:10.4081/ejtm.2022.10736

Contact Dermatitis. 2022 Oct 4. doi: 10.1111/cod.14230. Online ahead of print.

ABSTRACT

BACKGROUND: This study investigated cases diagnosed as allergic contact dermatitis (ACD) in emergency departments (EDs) and management.

METHODS: A multi-site retrospective study of patients attending EDs in metropolitan Melbourne between July 2017 and June 2018 was performed. Using International Statistical Classification of Disease-10 (ICD-10) codes, the Victorian Agency for Health Information generated a list of cases of contact dermatitis (CD). Demographic and clinical data were analysed.

RESULTS: 228 patients from 14 different sites were diagnosed with ACD. Hair dyes caused the most cases, and one such case was admitted to hospital. It was apparent from the specified causes that cases of irritant CD were misdiagnosed as ACD. There were significant differences in management with dermatology input, with dermatologists more often advising oral corticosteroids (33.3% vs 14.5%, p= 0.004) topical corticosteroids (92.9% vs 38.7% p <0.01), emollients (38.1% vs 20.4%, p = 0.01) and less often advising antihistamines (16.7% vs 44.6%, p <0.001). With dermatology input, potent or very potent steroids were more likely to be prescribed (69.3% vs 11.1%, p < 0.001); without, a mild potency steroid was more likely to be prescribed (63.9% vs 4%, p=0.01).

CONCLUSION: Improved understanding, diagnosis and management of CD is needed in EDs. This article is protected by copyright. All rights reserved.

PMID:36193797 | DOI:10.1111/cod.14230