Tag: nevin manimala

Pharmacol Rep. 2021 Jun 5. doi: 10.1007/s43440-021-00288-2. Online ahead of print.

ABSTRACT

BACKGROUND: The strong inter-individual pharmacokinetic variability and the narrow therapeutic window of tacrolimus (TAC) have hampered the clinical application. Gene polymorphisms play an important role in TAC pharmacokinetics. Here, we investigate the influence of genotypes of IL-10, CYP3A5, CYP2C8, and ABCB1 on dose-adjusted trough blood concentrations (the C₀/D ratio) of TAC to reveal unclear genetic factors that may affect TAC dose requirements for renal transplant recipients.

METHODS: Genetic polymorphisms of IL-10, CYP3A5, CYP2C8, and ABCB1 in 188 renal transplant recipients were determined using Kompetitive Allele Specific PCR (KASP). Statistical analysis was applied to examine the effect of genetic variation on the TAC C₀/D at 5, 10, 15, and 30 days after transplantation.

RESULTS: Recipients carrying the IL-10 -819C > T TT genotype showed a significantly higher TAC C₀/D than those with the TC/CC genotype (p < 0.05). Additionally, the TAC C₀/D values of recipients with the capacity for low IL-10 activity (-819 TT) engrafted with CYP3A5 non-expressers were higher compared to the intermediate/high activity of IL-10 -819C > T TC or CC carrying CYP3A5 expressers, and the difference was statistically significant at different time points (p < 0.05).

CONCLUSIONS: Genetic polymorphisms of IL-10 -819C > T and CYP3A5 6986A > G influence the TAC C₀/D, which may contribute to variation in TAC dose requirements during the early post-transplantation period. Detecting IL-10 -819C > T and CYP3A5 6986A > G polymorphisms may allow determination of individualized tacrolimus dosage regimens for renal transplant recipients during the early post-transplantation period.

PMID:34089513 | DOI:10.1007/s43440-021-00288-2

Radiol Med. 2021 Jun 5. doi: 10.1007/s11547-021-01371-7. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate CT and laboratory changes in COVID-19 patients treated with tocilizumab, compared to a control group, throughout a combined semiquantitative and texture analysis of images.

MATERIALS AND METHODS: From March 11 to April 20, 2020, 57 SARS-CoV-2 positive patients were retrospectively compared: group T (n = 30) receiving tocilizumab and group non-T (n = 27) undergoing only antivirals/antimalarials. Chest-CT and laboratory findings were analyzed before and after treatment. CT evaluation included both semiquantitative scoring and texture analysis of all parenchymal lesions. Survival and recovery analyses were also provided with Kaplan-Meier method.

RESULTS: In group T, no significant differences were found for CT score after treatment, while several texture features significantly changed, including mean attenuation (p < 0.0001), skewness (p < 0.0001), entropy (p = 0.0146) and higher-order parameters, suggesting considerable fading of parenchymal lesions. PaO₂/FiO₂ mean value significantly increased after treatment, from 240 ± 93 to 363 ± 107 (p = 0.0003), with parallel decrease in inflammatory biomarkers (CRP, D-dimer and LDH). In group non-T, CT scoring, texture and laboratory parameters showed significant worsening at follow-up. Findings were clinically associated with opposite trends between two groups, with reduction of severe cases in group T (from 21/30 to 5/30; p < 0.0001) as compared to a significant worsening in group non-T (severe cases increasing from 6/27 to 14/27; p = 0.0473). Probability of discharge was significantly higher in group T (p < 0.0001), as well as survival rate, although not statistically significant.

CONCLUSIONS: Our results suggest the potential role of CT texture analysis for assessing response to treatment in COVID-19 pneumonia, using Tocilizumab, as compared to semiquantitative evaluation, providing insight into the intrinsic parenchymal changes.

PMID:34089436 | DOI:10.1007/s11547-021-01371-7

Int J Comput Assist Radiol Surg. 2021 Jun 5. doi: 10.1007/s11548-021-02386-1. Online ahead of print.

ABSTRACT

PURPOSE: Transcranial magnetic stimulation (TMS) is a growing therapy for a variety of psychiatric and neurological disorders that arise from or are modulated by cortical regions of the brain represented by singular 3D target points. These target points are often determined manually with assistance from a pre-operative T1-weighted MRI, although there is growing interest in automatic target point localisation using an atlas. However, both approaches can be time-consuming which has an effect on the clinical workflow, and the latter does not take into account patient variability such as the varying number of cortical gyri where these targets are located.

METHODS: This paper proposes a multi-resolution convolutional neural network for point localisation in MR images for a priori defined points in increasingly finely resolved versions of the input image. This approach is both fast and highly memory efficient, allowing it to run in high-throughput centres, and has the capability of distinguishing between patients with high levels of anatomical variability.

RESULTS: Preliminary experiments have found the accuracy of this network to be [Formula: see text] mm, compared to [Formula: see text] mm for deformable registration and [Formula: see text] mm for a human expert. For most treatment points, the human expert and proposed CNN statistically significantly outperform registration, but neither statistically significantly outperforms the other, suggesting that the proposed network has human-level performance.

CONCLUSIONS: The human-level performance of this network indicates that it can improve TMS planning by automatically localising target points in seconds, avoiding more time-consuming registration or manual point localisation processes. This is particularly beneficial for out-of-hospital centres with limited computational resources where TMS is increasingly being administered.

PMID:34089439 | DOI:10.1007/s11548-021-02386-1

Cardiovasc Drugs Ther. 2021 Jun 5. doi: 10.1007/s10557-021-07209-8. Online ahead of print.

ABSTRACT

PURPOSE: Atrial high-rate episodes (AHREs) recorded with cardiac implantable electronic devices (CIEDs) have been associated with the development of clinical atrial fibrillation (AF) and increase in stroke and death risk. We sought to perform a systematic review with a meta-analysis to evaluate the prevalence of AHREs detected by CIEDs, their association with stroke risk, development of clinical AF, and mortality among patients without a documented history of AF.

METHODS: We searched several databases, ClinicalTrials.gov, references of reviews, and meeting abstract books without any language restrictions up to 9 September 2020. We studied patients with CIEDs in whom AHREs were detected. Exclusion criterion was AF history. Our primary outcome was the risk of ischemic stroke in patients with AHREs.

RESULTS: We deemed eligible eight studies for the meta-analysis enrolling a total of 4322 patients with CIED and without a documented AF history. The overall AHRE incidence ratio was estimated to be 17.56 (95% CI, 8.61 to 35.79) cases per 100 person-years. Evidence of moderate certainty suggests that patients with documented AHREs were 4.45 times (95% CI 2.87-6.91) more likely to develop clinical AF. Evidence of low confidence suggests that AHREs were associated with a 1.90-fold increased stroke risk (95% CI 1.19-3.05). AHREs were not associated with a statistically significant increased mortality risk.

CONCLUSION: The present systematic review and meta-analysis demonstrated that among patients without a documented history of AF, the detection of AHREs by CIEDs was associated with significant increased risk of clinical AF and stroke.

REGISTRATION NUMBER (DOI): Available in https://doi.org/10.17605/OSF.IO/ZRF6M .

PMID:34089429 | DOI:10.1007/s10557-021-07209-8

Ecohealth. 2021 Jun 5. doi: 10.1007/s10393-021-01523-1. Online ahead of print.

ABSTRACT

Soil microbes are important for public health. Increasing urbanisation is adversely affecting soil microbiota, which may be contributing to the global rise of immune-related diseases. Fungi are key components of urban environments that can be negatively impacted by altered land-use, land-management and climate change, and are implicated in the development and exacerbation of non-communicable diseases such as allergy, asthma and chronic inflammatory conditions. Fungal metagenomics is building knowledge on fungi within different environments (the environmental mycobiome), fungi on and within the human body (the human mycobiome), and their association with disease. Here, we demonstrate the added value of a multi-region metabarcoding approach to analyse soil mycobiomes from five urban greenspaces (lawns, parklands, bareground, young forest and old forest). While results were comparable across the three regions (ITS1, ITS2 and LSU), each identified additional fungal taxa that were unique to the region. Combining the results therefore provided a more comprehensive analysis across all fungal taxonomic ranks, identifying statistically significant differences in the fungal composition of the five soil types. Assignment of fungal taxa into ecological guilds revealed those differences of biological relevance to public health. The greatest differences were between the soil mycobiome of lawns and forests. Of most concern was the significant increase in the known human allergens Alternaria, Bipolaris, Cladosporium and Fusarium within urban lawn and parkland vs forest soils. By improving our understanding of local variations in fungal taxa across urban greenspaces, we have the potential to boost the health of local residents through improved urban planning.

PMID:34089413 | DOI:10.1007/s10393-021-01523-1

J Relig Health. 2021 Jun 5. doi: 10.1007/s10943-021-01301-x. Online ahead of print.

ABSTRACT

The aim of this study was to examine the effects of sexual behaviour, intercourse, satisfaction-related myths and spirituality on sexual dysfunctions in Muslim pregnant women. The study had a descriptive, cross-sectional and correlational design and was performed with 215 Muslim pregnant women. Descriptive statistics and multiple regression analyses were utilized for data analysis. As a result of the multiple regression analyses, sexual dysfunctions were most affected by sexual behaviour myths and least affected by perceived spirituality. It can be suggested that sexuality should be incorporated into prenatal care and counselling.

PMID:34089421 | DOI:10.1007/s10943-021-01301-x

Trop Anim Health Prod. 2021 Jun 5;53(3):342. doi: 10.1007/s11250-021-02782-4.

ABSTRACT

This study was designed to identify single-nucleotide polymorphisms (SNPs) of some candidate genes related to lipid metabolism and their association with carcass fat in male crossbred lambs. Hence, 96 of almost 11-month-old Booroola Merino-Afshari crossbred lambs (first-generation backcross) were used by considering their phenotypic carcass traits. Then, DNA was extracted and DNA targets were amplified using designed specific primers by PCR procedure. Identification of potential SNPs was done by a direct sequencing method for LEP, FABP4, DGAT1, GH, and TRIB3 genes using the sequencing-RFLP procedure. Then, the most probable statistical models based on additive and genotypic effects of identified SNPs in each trait were obtained by the Bayesian model averaging (BMA) approach of R software (Ver. 3.3.1) to assess the association of SNPs with traits. Detected SNPs in this study included two SNPs in exon 3 of LEP, one SNP in exon 2 of TRIB3, one SNP in intron 2 of FABP4, one SNP in 5′ UTR of DGAT1, and two SNPs in 3′ UTR of GH genes. For carcass weight trait, one of the identified SNP genotypes in the LEP (c.587G > A) had a higher probability in the model. Carcass weight of lambs with GA genotype was 2.46 kg heavier than GG genotype. Also, two genes of TRIB3 and GH2 had the highest probability in the models of fat tail and waste weight, respectively. Based on the results, these polymorphisms can be used in the marker-assisted selection of breeding programs and designing DNA chips for genomic selection.

PMID:34089397 | DOI:10.1007/s11250-021-02782-4

AMB Express. 2021 Jun 5;11(1):82. doi: 10.1186/s13568-021-01243-3.

ABSTRACT

The current study was aimed at investigating the prevalence of the mutations upstream of the oprD coding region and its promoters among imipenem-resistant and sensitive Pseudomonas aeruginosa isolated from educational hospitals in Yazd City, Iran. All isolates were identified by the conventional biochemical tests. Then, the antibiotic resistance of these isolates was determined using the disk diffusion method according to the CLSI guidelines. Also, the E.test was performed to determine the minimum inhibitory concentrations (MIC) of imipenem. The mutations of this gene were recognized by the amplification of this region and subsequently sequenced. Sequencing of the genomic region upstream of oprD these regions were done in the 29 clinical strains. Statistical analysis was done by the statistical software SPSS-18. Seventy (77.7%) of isolates had MIC ≥ 16 and were resistant to imipenem. Mutations of the upstream of the oprD gene and its promoters were seen in 25 (86.2%) isolates and 4 isolates had no mutation. One isolate had a base substitution A→Cat nt 25 in the coding region and this isolate had a point mutation leading to an amino acid change at positions 9 (I→L). Our study results indicated that none of the strains had mutation in Shine-Dalgarno and the point mutations were the most common mutations upstream of the oprD coding region among P. aeruginosa isolates. Mutations were observed in imipenem-resistant isolates and it seems this mechanism is effective in resistance of isolates to imipenem and this confirmed that the indiscriminate use of antibiotic should be controlled.

PMID:34089411 | DOI:10.1186/s13568-021-01243-3

J Patient Rep Outcomes. 2021 Jun 5;5(1):43. doi: 10.1186/s41687-021-00312-2.

ABSTRACT

BACKGROUND: Disparities in US physician burnout rates across age, gender, and specialty groups as measured by the Maslach Burnout Inventory-Human Services Survey for Medical Personnel (MBI) are well documented. We evaluated whether disparities in US physician burnout are explained by differences in the MBI’s functioning across physician age, gender, and specialty groups.

METHODS: We assessed the measurement equivalence of the MBI across age, gender, and specialty groups in multi-group item response theory- (IRT-) based differential item functioning (DIF) analyses using secondary, cross-sectional survey data from US physicians (n = 6577). We detected DIF using two IRT-based methods and assessed its impact by estimating the overall average difference in groups’ subscale scores attributable to DIF. We assessed DIF’s practical significance by comparing differences in individuals’ subscale scores and burnout prevalence estimates from models unadjusted and adjusted for DIF.

RESULTS: We detected statistically significant age-, gender-, and specialty- DIF in all but one MBI item. However, in all cases, average differences in expected subscale-level scores due to DIF were < 0.10 SD on each subscale. Differences in physicians’ individual-level subscale scores and burnout symptom prevalence estimates across DIF- adjusted and unadjusted IRT models were also small (in all cases, mean absolute differences in individual subscale scores were < 0.04 z-score units; prevalence estimates differed by < 0.70%).

CONCLUSIONS: Age-, gender-, and specialty-related disparities in US physician burnout are not explained by differences in the MBI’s functioning across these demographic groups. Our findings support the use of the MBI as a valid tool to assess age-, gender-, and specialty-related disparities in US physician burnout.

PMID:34089412 | DOI:10.1186/s41687-021-00312-2

Cancer Immunol Immunother. 2021 Jun 5. doi: 10.1007/s00262-021-02954-z. Online ahead of print.

ABSTRACT

We have previously revealed the overexpression of Wilms’ tumor gene 1 (WT1) in malignant glioma and developed WT1 peptide vaccine cancer immunotherapy. A phase II clinical trial indicated the clinical efficacy of the WT1 peptide vaccine for recurrent malignant glioma. Here, we aimed to investigate the immunological microenvironment in glioma tissues before and after WT1 peptide vaccine treatment. Paired tissue samples were obtained from 20 malignant glioma patients who had received the WT1 peptide vaccine for > 3 months and experienced tumor progression, confirmed radiographically and/or clinically, during vaccination. We discovered that the expression of WT1 and HLA class I antigens in the tumor cells significantly decreased after vaccination. Maintenance of WT1 expression, which is the target molecule of immunotherapy, in tumor cells during the vaccination period was significantly associated with a longer progression-free and overall survival. A high expression of HLA class I antigens and low CD4⁺/CD8⁺ tumor-infiltrating lymphocytes (TIL) ratio in pre-vaccination specimens, were also associated with a good prognosis. No statistically significant difference existed in the number of infiltrating CD3⁺ or CD8⁺ T cells between the pre- and post-vaccination specimens, whereas the number of infiltrating CD4⁺ T cells significantly decreased in the post-vaccination specimens. This study provides insight into the mechanisms of intra-tumoral immune reaction/escape during WT1 peptide vaccine treatment and suggests potential clinical strategies for cancer immunotherapy.

PMID:34089373 | DOI:10.1007/s00262-021-02954-z