Category: Nevin Manimala

Water Environ Res. 2022 Nov 7;94(11):e10810. doi: 10.1002/wer.10810. Online ahead of print.

ABSTRACT

The Feng-Sang River is a metropolitan river in Kaohsiung City, Taiwan. In this study, Feng-Sang River sediments were analyzed to investigate the distributions and sources of polycyclic aromatic hydrocarbons (PAHs). The Sediment Quality Guidelines (SQGs), potentially carcinogenic PAHs (TEQ^carc ), and toxic equivalence quotient (TEQ) were applied to evaluate influences of PAHs on ecosystems and microbial diversities. Results indicate that PAHs concentrations varied between seasons and locations. The concentrations of ∑₁₆ PAHs ranged from 73.6 to 603.8 ng/kg in dry seasons and from 2.3 to 199.3 ng/kg in wet seasons. This could be because of the flushing effect during wet seasons, which caused the movement and dilution of the PAH-contaminated sediments. Diagnostic ratio analysis infers that high PAHs levels were generated by combustion processes and vehicle traffic, and results from multivariate descriptive statistical analysis also demonstrate that the vehicular traffic pollution could be the major emission source of PAHs contamination. Comparisons of PAHs with SQGs indicate that PAHs concentrations in sediment were below the effects range low (ERL) values, and thus, the immediate threat to organisms might not be significant. The diagnostic ratio analyses are effective methods for PAH source appointment. The metagenomic assay results imply that sediments contained essential microbial species with eminent diversity. The detected PAH-degrading bacteria (Desulfatiglans, Dechloromonas, Sphingomonas, Methylobacterium, Rhodobacter, Clostridium, and Exiguobacterium) played a key role in PAHs biotransformation, and Dechloromonas and Rhodobacter had a higher relative abundance. Results of microbial diversity analyses indicate that the contaminated environment induced the changes of governing microbial groups in sediments. PRACTITIONER POINTS: Diagnostic ratio analyses are effective methods for PAHs source appointment. Microbial composition in sediments are highly affected by anthropogenic pollution. Combustion and vehicle traffic contribute to urban river sediments pollution by PAHs. Dechloromonas and Rhodobacter are dominant PAHs-degrading bacteria in sediments.

PMID:36433735 | DOI:10.1002/wer.10810

Clin Physiol Funct Imaging. 2022 Nov 26. doi: 10.1111/cpf.12804. Online ahead of print.

ABSTRACT

This study was designed to compare the effects of core stabilisation and auxiliary respiratory muscle strengthening exercises on oxygen consumption and respiratory parameters. A total of 51 participants were divided into 3 groups with block randomization method according to age and gender: Core Stabilisation (CS) Group (n = 17), Auxiliary Respiratory Muscles Exercise (ARM) Group (n = 17) and Control (C) Group (n = 17). VO₂ max, first second of forced expiration (FEV1)/Forced vital capacity (FVC), and maximal voluntary ventilation (MVV) values were evaluated before and after the study. CS and ARM strengthening exercises were applied 3 days a week for 6 weeks. The increase in the FEV1/VC values was higher in the CS and ARM groups than in the C group (p<0.05), whereas no statistically significant difference was observed between the ARM and CS groups (p<0.05). There was no statistically significant difference between the groups in terms of VO₂ max values before and after the study (p>0.05). The increase in the MVV values was higher in the CS and ARM groups than in the C group (p<0.05), whereas no statistically significant difference was observed between the ARM and CS groups (p>0.05). CS and ARM exercises had positive effects on FEV1/FVC and MVV. This article is protected by copyright. All rights reserved.

PMID:36433716 | DOI:10.1111/cpf.12804

Clin Infect Dis. 2022 Nov 26:ciac922. doi: 10.1093/cid/ciac922. Online ahead of print.

ABSTRACT

The United States CDC defines a county metric of COVID-19 Community Levels to inform public health measures. We find that the COVID-19 Community Levels vary frequently over time, which may not be optimal for decision making. Alternative metric formulations that do not compromise predictive ability are shown to reduce variability.

PMID:36433715 | DOI:10.1093/cid/ciac922

J Magn Reson Imaging. 2022 Nov 26. doi: 10.1002/jmri.28533. Online ahead of print.

ABSTRACT

BACKGROUND: CAIPIRINHA-Dixon-TWIST-VIBE (CDTV) dynamic contrast-enhanced MRI (DCE-MRI) can be used to characterize breast cancer. However, the influence of the clinicopathologic factors and molecular subtypes of invasive breast carcinoma (IDC) on the model-free and model-based parameters has not been investigated.

PURPOSE: To compare model-free and model-based parameters of CDTV DCE-MRI with both clinicopathologic factors and molecular subtypes of IDC.

STUDY TYPE: Prospective.

POPULATION: A total of 152 patients (mean age, 52 years) with IDC including 42 luminal A, 64 luminal B, 22 human epidermal growth factor receptor-2 (HER2) positive, and 24 triple-negative subtypes.

FIELD STRENGTH/SEQUENCE: A 3 T; turbo-FLASH, Dixon VIBE, and CDTV.

ASSESSMENT: Model-free parameters (initial enhancement rate [IER] and maximum slope [MS]) were estimated from the time-intensity curve. The mean, minimum, maximum, and range between the minimum and maximum values of inline model-based parameters (K^trans , k_ep , and v_e ) were measured to assess intratumoral heterogeneity of IDC lesions.

STATISTICAL TESTS: Student’s t tests, Mann-Whitney U tests, Kruskal-Wallis tests, post hoc Steel-Dwass tests, and receiver operating characteristic (ROC) curves. P < 0.05 was considered significant.

RESULTS: No significant differences in IER and MS values were seen among the clinicopathologic factors and molecular subtypes (Bonferroni-corrected P = 0.011-0.862, P = 0.145-0.601, respectively). The minimum k_ep values in HER2-positive IDC were significantly lower than those in HER2-negative IDC. The mean and range k_ep values were independent predictors for distinguishing the high (grade 3) and low (grade 1 or 2) nuclear grade groups according to multivariable analyses. The post hoc test showed that the k_ep minimum and k_ep range values were significantly different between luminal A and HER2-positive tumor subtypes, yielding an area-under-the-curve of 0.820.

DATA CONCLUSION: Compared with the model-free parameters, inline k_ep related model-based parameters on CDTV DCE-MRI can be applied as a feasible tool to differentiate luminal A from HER2-positive breast cancers.

EVIDENCE LEVEL: 2.

TECHNICAL EFFICACY: Stage 2.

PMID:36433714 | DOI:10.1002/jmri.28533

J Eur Acad Dermatol Venereol. 2022 Nov 25. doi: 10.1111/jdv.18774. Online ahead of print.

ABSTRACT

BACKGROUND: Low-risk basal cell carcinomas (BCCs) are to an increasing extent diagnosed by dermatologists through dermoscopic examination only and treated with non-surgical methods. Reports on increasing incidence as well as trends regarding subtypes, anatomical sites and differences related to gender are based solely on histopathologically verified tumours. How unreported clinically diagnosed BCCs affect the epidemiological data has not been sufficiently investigated.

OBJECTIVES: To analyze tumour and patient characteristics of clinically diagnosed versus histopathologically confirmed primary BCCs and to make a gross estimate on how unreported BCCs could influence the total number of new cases.

METHODS: We retrospectively reviewed all primary BCCs diagnosed in 2016 at the Department of Dermatology, Sahlgrenska University Hospital in Gothenburg, Sweden. We also reviewed all histopathologically verified primary BCCs at the two largest pathology laboratories in Western Sweden during the same year to estimate the proportion of BCCs diagnosed by dermatologists.

RESULTS: In total, 2,365 primary BCCs were diagnosed at our center. More than half of these tumours were clinically diagnosed (55.8%). Superficial subtype (41.7%), location on the trunk (46.3%) and destructive treatment methods (60.0%) were most common. Reports from the two pathology laboratories showed that histopathologically verified BCCs (n=5,837) were more commonly of the infiltrative or nodular subtype and located in the head and neck area. Dermatologists managed 56.0% of them.

CONCLUSIONS: This study indicates that a substantial number of BCCs are not visualized in the official statistics which are solely based on reports from pathology laboratories. When taking clinically diagnosed tumours into account, truncal location and superficial subtype are more common than previously believed. Further, based on regional calculations, the real burden of BCC in Sweden might be up to 70% higher than what is reported in official statistics.

PMID:36433707 | DOI:10.1111/jdv.18774

Drug Dev Res. 2022 Nov 25. doi: 10.1002/ddr.22012. Online ahead of print.

ABSTRACT

Rab GTPases are critical regulators of protein trafficking in the cell. To ensure proper cellular localization and function, Rab proteins must undergo a posttranslational modification, termed geranylgeranylation. In the isoprenoid biosynthesis pathway, the enzyme geranylgeranyl diphosphate synthase (GGDPS) generates the 20-carbon isoprenoid donor (geranylgeranyl pyrophosphate [GGPP]), which is utilized in the prenylation of Rab proteins. We have pursued the development of GGDPS inhibitors (GGSI) as a novel means to target Rab activity in cancer cells. Osteosarcoma (OS) and Ewing sarcoma (ES) are aggressive childhood bone cancers with stagnant survival statistics and limited treatment options. Here we show that GGSI treatment induces markers of the unfolded protein response (UPR) and triggers apoptotic cell death in a variety of OS and ES cell lines. Confirmation that these effects were secondary to cellular depletion of GGPP and disruption of Rab geranylgeranylation was confirmed via experiments using exogenous GGPP or specific geranylgeranyl transferase inhibitors. Furthermore, GGSI treatment disrupts cellular migration and invasion in vitro. Metabolomic profiles of OS and ES cell lines identify distinct changes in purine metabolism in GGSI-treated cells. Lastly, we demonstrate that GGSI treatment slows tumor growth in a mouse model of ES. Collectively, these studies support further development of GGSIs as a novel treatment for OS and ES.

PMID:36433690 | DOI:10.1002/ddr.22012

J Eur Acad Dermatol Venereol. 2022 Nov 25. doi: 10.1111/jdv.18779. Online ahead of print.

ABSTRACT

BACKGROUND: PD-1 antibodies and BRAF+MEK inhibitors are widely used for adjuvant therapy of fully resected high-risk melanoma. Little is known about treatment efficacy outside of phase III trials. This real-world study reports on clinical outcomes of modern adjuvant melanoma treatment in specialized skin cancer centers in Germany, Austria and Switzerland.

METHODS: Multicenter, retrospective study investigating stage III-IV melanoma patients receiving adjuvant nivolumab (NIV), pembrolizumab (PEM) or dabrafenib+trametinib (D+T) between 1/2017 and 10/2021. The primary endpoint was 12-month recurrence free survival (RFS). Further analyses included descriptive and correlative statistics, and a multivariate linear-regression machine learning model to assess the risk of early melanoma recurrence.

RESULTS: 1198 patients from 39 skin cancer centers from Germany, Austria and Switzerland were analyzed. The vast majority received anti PD-1 therapies (n=1003). 12-month RFS for anti PD-1 and BRAF+MEK inhibitor treated patients were 78.1% and 86.5% respectively (hazard ratio [HR] 1.998 [95%CI 1.335-2.991]; p=0.001). There was no statistically significant difference in overall survival in anti PD-1 (95.8%) and BRAF+MEK inhibitor (96.9%) treated patients (p>0.05) during the median follow-up of 17 months. Data indicates that anti PD-1 treated patients who develop immune-related adverse events (irAEs) have lower recurrence rates compared to patients with no irAEs (HR 0.578 [95%CI 0.443-0.754], p=0.001). BRAF mutation status did not affect overall efficacy of anti PD-1 treatment (p>0.05). In both, anti PD-1 and BRAF+MEK inhibitor treated cohorts, data did not show any difference in 12-month RFS and 12-month OS comparing patients receiving total lymph node dissection versus sentinel lymph node biopsy only (p>0.05). The recurrence prediction model reached high specificity but only low sensitivity with an AUC=0.65. No new safety signals were detected. Overall, recorded numbers and severity of adverse events were lower than reported in pivotal phase III trials.

CONCLUSIONS: Despite recent advances in adjuvant melanoma treatment, early recurrence remains a significant clinical challenge. This study shows that total lymph node dissection does not reduce the risk of early melanoma recurrence and should only be considered in selected patients. Data further highlight that variables collected during clinical routine are unlikely to allow for a clinically relevant prediction of individual recurrence risk.

PMID:36433688 | DOI:10.1111/jdv.18779

Health Promot J Austr. 2022 Nov 25. doi: 10.1002/hpja.682. Online ahead of print.

ABSTRACT

ISSUE ADDRESSED: Locating fast-food outlets near schools is a potential public health risk to schoolchildren, given the easy access and repeated exposure to energy-dense, nutrient-poor foods they provide. Fast-food outlet availability near schools has not been previously investigated in Perth, Western Australia. This study aimed to quantify fast-food outlet availability near Perth schools and determine whether differences in area-level disadvantage and school type exist.

METHODS: Fast-food outlet locations were sourced from Perth Local Governments in 2018/2019. All Perth Primary (n=454), Secondary (n=107) and K-12 (n=94) schools were assigned an area-level disadvantage decile ranking based on the Australian Bureau of Statistics Socio-Economic Index for Areas (SEIFA). Regression models assessed whether fast-food outlet availability within 400m, 800m and 1km of schools differed by school type (i.e., Primary/Secondary/K-12) or SEIFA.

RESULTS: Secondary schools were significantly more likely than Primary and K-12 schools to have a higher presence and density of fast-food outlets and the ‘Top 4’ fast-food outlet chains (McDonalds, Hungry Jacks, KFC and Red Rooster) nearby. Schools located in low socio-economic status (SES) areas had a significantly higher density of fast-food outlets within 400m, and ‘Top 4’ fast-food outlet chains within 400m and 1km, than schools located in high SES area.

CONCLUSIONS: Perth schools are surrounded by fast-food outlets with densities significantly higher around secondary schools and schools located in lower SES areas.

SO WHAT: Policies and regulations aimed at reducing fast-food outlets near schools is an essential strategy to improve dietary intakes and reduce obesity in schoolchildren.

PMID:36433680 | DOI:10.1002/hpja.682

J Clin Pharmacol. 2022 Nov 25. doi: 10.1002/jcph.2183. Online ahead of print.

ABSTRACT

This study was performed to detect the expression of ceruloplasmin in the peripheral blood of patients with drug-resistant epilepsy and explore the mechanisms of iron metabolism disorder in drug-resistant epilepsy. The expression levels of ceruloplasmin mRNA and ceruloplasmin protein in the peripheral blood of the three groups were detected using real-time fluorescence-based quantitative polymerase chain reaction and Western blot. The differences in the expression of ceruloplasmin mRNA of different seizure frequencies and types, electroencephalogram (EEG) abnormal discharges, and different medication methods were analyzed and compared. The relative expression of ceruloplasmin mRNA and ceruloplasmin protein in the drug-resistant epilepsy group was significantly higher than that in the drug responsive group and higher in the drug responsive group compared with the normal group. The relative expression of ceruloplasmin mRNA in patients with epilepsy using different medication methods was statistically significant. Patients who received a combination of two or three drugs exhibited a higher expression than those treated with a single-drug treatment, whereas those who received a combination of three drugs had a higher expression than those with two drugs. The increased expression of ceruloplasmin in the peripheral blood of patients with drug-resistant epilepsy was closely related to the different medication methods, but no obvious correlation with epileptic seizure frequencies or types and abnormal EEG discharges was identified. The increased expression of ceruloplasmin enhanced iron oxidative damage and may be the potential mechanism of drug-resistant epilepsy and may be one of the drug resistance indicators for combination drugs when treating drug-resistant epilepsy. This article is protected by copyright. All rights reserved.

PMID:36433654 | DOI:10.1002/jcph.2183

Mol Ecol. 2022 Nov 25. doi: 10.1111/mec.16793. Online ahead of print.

ABSTRACT

The term “haplotype block” is commonly used in the developing field of haplotype-based inference methods. We argue that the term should be defined based on the structure of the Ancestral Recombination Graph (ARG), which contains complete information on the ancestry of a sample. We use simulated examples to demonstrate key features of the relation between haplotype blocks and ancestral structure, emphasising the stochasticity of the processes that generate them. Even the simplest cases of neutrality or of a “hard” selective sweep produce a rich structure, often missed by commonly used statistics. We highlight a number of novel methods for inferring haplotype structure, based on the full ARG, or on a sequence of trees, and illustrate how they can be used to define haplotype blocks using an empirical dataset. While the advent of new, computational efficient methods makes it possible to apply these concepts broadly, they (and additional new methods) could benefit from adding features to explore haplotype blocks, as we define them. Understanding and applying the concept of the haplotype block will be essential to fully exploit long and linked-read sequencing technologies.

PMID:36433653 | DOI:10.1111/mec.16793