Publications by authors named "Shahzad Ahmad"

108 Publications

Frailty as a Predictor of Device Choice and Mortality in Older Cardiac Resynchronization Therapy Recipients.

Circ Arrhythm Electrophysiol 2021 Sep 20:CIRCEP121010185. Epub 2021 Sep 20.

Department of Medicine, Heart and Vascular Institute, University of Pittsburgh Medical Center, PA (S.A., D.M., A.H., M.A., D.E.F., S.S.).

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCEP.121.010185DOI Listing
September 2021

Genome-wide association study of frontotemporal dementia identifies a C9ORF72 haplotype with a median of 12-G4C2 repeats that predisposes to pathological repeat expansions.

Transl Psychiatry 2021 Sep 2;11(1):451. Epub 2021 Sep 2.

Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.

Genetic factors play a major role in frontotemporal dementia (FTD). The majority of FTD cannot be genetically explained yet and it is likely that there are still FTD risk loci to be discovered. Common variants have been identified with genome-wide association studies (GWAS), but these studies have not systematically searched for rare variants. To identify rare and new common variant FTD risk loci and provide more insight into the heritability of C9ORF72-related FTD, we performed a GWAS consisting of 354 FTD patients (including and excluding N = 28 pathological repeat carriers) and 4209 control subjects. The Haplotype Reference Consortium was used as reference panel, allowing for the imputation of rare genetic variants. Two rare genetic variants nearby C9ORF72 were strongly associated with FTD in the discovery (rs147211831: OR = 4.8, P = 9.2 × 10, rs117204439: OR = 4.9, P = 6.0 × 10) and replication analysis (P < 1.1 × 10). These variants also significantly associated with amyotrophic lateral sclerosis in a publicly available dataset. Using haplotype analyses in 1200 individuals, we showed that these variants tag a sub-haplotype of the founder haplotype of the repeat expansion that was previously found to be present in virtually all pathological C9ORF72 GC repeat lengths. This new risk haplotype was 10 times more likely to contain a C9ORF72 pathological repeat length compared to founder haplotypes without one of the two risk variants (~22% versus ~2%; P = 7.70 × 10). In haplotypes without a pathologic expansion, the founder risk haplotype had a higher number of repeats (median = 12 repeats) compared to the founder haplotype without the risk variants (median = 8 repeats) (P = 2.05 × 10). In conclusion, the identified risk haplotype, which is carried by ~4% of all individuals, is a major risk factor for pathological repeat lengths of C9ORF72 GC. These findings strongly indicate that longer C9ORF72 repeats are unstable and more likely to convert to germline pathological C9ORF72 repeat expansions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41398-021-01577-3DOI Listing
September 2021

Safety and Efficacy of Radiofrequency Ablation of Thyroid Nodules-Expanding Treatment Options in the United States.

J Endocr Soc 2021 Aug 10;5(8):bvab110. Epub 2021 Jun 10.

The Thyroid Clinic, Salt Lake City, UT 84124, USA.

Context: Radiofrequency ablation (RFA) has only recently gained popularity in the United States for treatment of thyroid nodules (TNs), with a limited number of patients having undergone the procedure in this country.

Objective: To evaluate the safety and efficacy of RFA of TNs performed in an outpatient setting in the United States.

Methods: This is a retrospective, single-center study of 53 patients who underwent RFA of 58 TNs between November 2018 and January 2021. The reduction in volume of nodule, cosmetic and symptomatic improvement, effect on thyroid function, and complications following RFA were assessed.

Results: Eleven out of 53 patients were excluded from the analysis. A total of 47 benign TNs (23 nonfunctioning thyroid nodules [NFTNs] and 24 autonomously functioning thyroid nodules [AFTNs]), were assessed after RFA. The median reduction in volume was 70.8% after a median follow-up period of 109 days, with symptomatic and cosmetic improvement ( < 0.0001). Compared with larger nodules, smaller nodules had greater volume reduction ( = 0.0266). RFA improved thyrotropin (TSH) in AFTNs ( value = 0.0015) and did not affect TSH in NFTNs ( value = 0.23). There were no major complications; however, 1 patient had self-limited local bleeding and another had transient voice change that recovered in 6 months.

Conclusion: RFA is a safe and efficacious treatment for symptomatic NFTNs and AFTNs in our population and is especially effective for smaller nodules. RFA should be considered an alternative for TNs in patients who cannot or do not want to undergo surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/jendso/bvab110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271212PMC
August 2021

Radiofrequency Ablation of Parathyroid Adenoma: A Novel Treatment Option for Primary Hyperparathyroidism.

AACE Clin Case Rep 2021 May-Jun;7(3):195-199. Epub 2021 Jan 13.

The Thyroid Clinic, Salt Lake City, Utah.

Objective: To present radiofrequency ablation (RFA) of parathyroid adenomas as a safe and effective management strategy for primary hyperparathyroidism in patients who are not eligible for surgery or those who do not want surgery.

Methods: The diagnosis of primary hyperparathyroidism was confirmed by laboratory investigations. A bone density scan showed osteoporosis, which was an indication for the surgical treatment of primary hyperparathyroidism. Ultrasonography of the neck was done to localize the parathyroid adenoma, after which RFA was performed to shrink the adenoma. Laboratory investigations were performed 10 days, 6 months, and 12 months after the procedure. A literature review was also conducted, and other reports of primary hyperparathyroidism cases treated with RFA were identified.

Results: Biochemical cure of primary hyperparathyroidism was achieved by normalization of calcium levels, resolution of symptoms, elimination of complications, and decrease in the volume of the parathyroid adenoma.

Conclusion: RFA of parathyroid adenomas is a viable alternative to parathyroidectomy in patients who do not meet the criteria for surgery or do not wish to undergo surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aace.2021.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165122PMC
January 2021

Multiomics integrative analysis identifies allele-specific blood biomarkers associated to Alzheimer's disease etiopathogenesis.

Aging (Albany NY) 2021 Apr 12;13(7):9277-9329. Epub 2021 Apr 12.

Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.

Alzheimer's disease (AD) is the most common form of dementia, currently affecting 35 million people worldwide. Apolipoprotein E (APOE) ε4 allele is the major risk factor for sporadic, late-onset AD (LOAD), which comprises over 95% of AD cases, increasing the risk of AD 4-12 fold. Despite this, the role of APOE in AD pathogenesis is still a mystery. Aiming for a better understanding of APOE-specific effects, the ADAPTED consortium analysed and integrated publicly available data of multiple OMICS technologies from both plasma and brain stratified by haplotype ( and ). Combining genome-wide association studies (GWAS) with differential mRNA and protein expression analyses and single-nuclei transcriptomics, we identified genes and pathways contributing to AD in both APOE dependent and independent fashion. Interestingly, we characterised a set of biomarkers showing plasma and brain consistent protein profiles and opposite trends in and AD cases that could constitute screening tools for a disease that lacks specific blood biomarkers. Beside the identification of APOE-specific signatures, our findings advocate that this novel approach, based on the concordance across OMIC layers and tissues, is an effective strategy for overcoming the limitations of often underpowered single-OMICS studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.202950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064208PMC
April 2021

Concentration and Localization of Fe and Zn in Wheat Grain as Affected by Its Application to Soil and Foliage.

Bull Environ Contam Toxicol 2021 May 26;106(5):852-858. Epub 2021 Mar 26.

Department of Botany, University of Agriculture, Faisalabad, Pakistan.

Nutritional status of people can be improved by enhancing zinc (Zn) and iron (Fe) content in cereals used as staple mainly in poor resource countries. Zinc and Fe were applied through soil and foliage in a study to biofortify wheat grains. Foliar application of both micronutrients increased the growth and grain vigor as compared to soil application and control. Also, foliar application significantly enhanced Zn and Fe concentration in grain pre-dominantly localized in aleurone layer. Exogeneous application of Fe and Zn was found beneficial for plant growth and enhanced Fe and Zn concentrations in grain, however aleurone layer and embryonic region of the grain showed higher accumulations than that in endosperm. Therefore, understanding of physiological and molecular pathways for uptake and localization of Fe and Zn in wheat grains need to be critically examined to improve their concentration in grain to achieve the biofortification targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00128-021-03183-xDOI Listing
May 2021

Common and Rare Variants Genetic Association Analysis of Circulating Neutrophil Extracellular Traps.

Front Immunol 2021 24;12:615527. Epub 2021 Feb 24.

Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands.

Introduction: Neutrophils contribute to host defense through different mechanisms, including the formation of neutrophil extracellular traps (NETs). The genetic background and underlying mechanisms contributing to NET formation remain unclear.

Materials And Methods: We performed a genome-wide association study (GWAS) and exome-sequencing analysis to identify common and rare genetic variants associated with plasma myeloperoxidase (MPO)-DNA complex levels, a biomarker for NETs, in the population-based Rotterdam Study cohort. GWAS was performed using haplotype reference consortium(HRC)-imputed genotypes of common variants in 3,514 individuals from the first and 2,076 individuals from the second cohort of the Rotterdam Study. We additionally performed exome-sequencing analysis in 960 individuals to investigate rare variants in candidate genes.

Results: The GWAS yielded suggestive associations (p-value < 5.0 × 10) of SNPs annotated to four genes. In the exome-sequencing analysis, a variant in gene was significantly associated with MPO-DNA complex levels (p-value < 3.06×10). Moreover, gene-based analysis showed ten genes () to be associated with MPO-DNA complex levels (p-value between 4.48 × 10 and 1.05 × 10). Pathway analysis of the identified genes showed their involvement in cellular development, molecular transport, RNA trafficking, cell-to-cell signaling and interaction, cellular growth and proliferation. Cancer was the top disease linked to the NET-associated genes.

Conclusion: In this first GWAS and exome-sequencing analysis of NETs levels, we found several genes that were associated with NETs. The precise mechanism of how these genes may contribute to neutrophil function or the formation of NETs remains unclear and should be further investigated in experimental studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.615527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944992PMC
July 2021

Emergence of plasmid-mediated mcr genes from Gram-negative bacteria at the human-animal interface.

Gut Pathog 2020 Nov 20;12(1):54. Epub 2020 Nov 20.

Department of Immunology, University of Health Sciences, Khayaban-e-Jamia Punjab, 54600, Lahore, Pakistan.

Background: The global emergence of plasmid-mediated colistin resistance (Col-R) conferred by mcr genes in gram-negative rods (GNRs) has jeopardized the last treatment option for multidrug-resistant bacterial infections in humans. This study aimed to assess the emergence of mcr gene-mediated Col-R in GNRs isolated from humans and animals in Pakistan.

Methods: Animal and clinical specimens collected from various sources were prospectively analysed using standard microbiological procedures. Pathogens were identified using the API 20E and API 20NE systems (bioMerieux). Minimum inhibitory concentration (MIC) against colistin was determined using the MIC detection methods, and multiplex polymerase chain reaction (PCR) was used to amplify the mcr-1 to mcr-5 genes.

Results: We isolated 126 (88.1%) animal and 17 (11.9%) human Col-R phenotypes, among which there was a significant association (P < 0.01) of Escherichia coli and Proteus mirabilis with animals and of Acinetobacter baumannii with humans. Animal strains exhibited statistically significant (P < 0.05) resistance to co-trimoxazole, chloramphenicol, and moxifloxacin, and the human pathogens exhibited statistically significant (P < 0.05) antibiotic resistance to cephalosporins, carbapenems, and piperacillin-tazobactam. For Col-R strains, MIC values were > 6 µg/mL and > 12 µg/mL for human and animal isolates, respectively. mcr genes were detected in 110 (76.9%) bacterial strains, of which 108 (98.2%) were mcr-1 and 2 (1.8%) were mcr-2.

Conclusions: The detection of a considerable number of mcr-1 and mcr-2 genes in animals is worrisome, as they are now being detected in clinical pathogens. The acquisition of mcr genes by colistin-susceptible bacteria could leave us in a post-antibiotic era.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13099-020-00392-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678191PMC
November 2020

Recent progress in engineering functional biohybrid robots actuated by living cells.

Acta Biomater 2021 02 5;121:29-40. Epub 2020 Dec 5.

Department of Mechanical Engineering, Xian Jiaotong University, 28 Xianning West Road, Xian Shaanxi 710049, China; State Key Lab for Manufacturing Systems Engineering, Xian Jiaotong University, Xian Shaanxi 710049, China.

Living cells are highly scalable biological actuators found in nature, and they are efficient technological solutions to actuate robotic systems. Recent advancements in biofabrication and tissue engineering have bridged the gap to interface muscle cells with artificial technology. In this review, we summarize the recent progress in engineering the attributes of individual components for the development of fully functional biohybrid robots. First, we address the fabrication of biological actuators for biohybrid robots with muscle cells and tissues, including cardiomyocytes, skeletal muscles, insect tissues, and neuromuscular tissues, in well-organized pattern of 2D sheets and 3D constructs. Next, we discuss the performance of biohybrid robots for various biomimetic tasks such as swimming, walking, gripping, and pumping. Finally, the challenges and future directions in the development of biohybrid robots are described from different viewpoints of living material engineering, multiscale modeling, 3D printing for manufacturing, and multifunctional robotic system development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.actbio.2020.12.002DOI Listing
February 2021

Acuities into tolerance mechanisms via different bioassay during Brassicaceae-Alternaria brassicicola interaction and its impact on yield.

PLoS One 2020 1;15(12):e0242545. Epub 2020 Dec 1.

Department of Plant Breeding and Genetics, Faculty of Agricultural Sciences and Technology, Bahauddin Zakariya University, Multan, Pakistan.

Heavy losses by dark leaf spot disease in oilseed Brassica have incited research towards identifying sources of genetic tolerance against causal pathogen, Alternaria brassicicola. Several morpho-molecular parameters were evaluated to test the performance of field mustard and rapeseed genotypes under artificial inoculation with this pathogen. During Brassica-Alternaria interaction, physio-biochemical defense response was witnessed in tolerant genotypes. Two tolerant genotypes (one for field mustard and one for rapeseed), i.e., EC250407 and EC1494 were identified. However, necrotic lesions were more prominent in susceptible genotypes with minimum chlorophyll (chlorophyll a, chlorophyll b and total chlorophyll) and carotenoids contents. Contrary to photosynthetic pigments, increase in total soluble protein (TSP) contents was observed with disease progression in susceptible genotypes. Tolerant genotypes of field mustard and rapeseed displayed remarkable increase in the activities of redox enzyme in infected leaves with least yield loss (6.47% and 5.74%) and disease severity index (DSI) of 2.9 and 2.1, respectively. However, yield/plant showed close association with other morpho-yield parameters, photosynthetic pigments and redox enzymes (superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD)) activities except silique length and TSP. Based on the results of morpho-biochemical analyses, redox enzymes and morphological parameters; their interplay is proposed to determine the tolerance outcome of the Brassica-A. brassicicola interaction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242545PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707606PMC
January 2021

Diabetes mellitus and urinary tract infection: Causative uropathogens, their antibiotic susceptibility pattern and the effects of glycemic status.

Pak J Med Sci 2020 Nov-Dec;36(7):1550-1557

Dr. Iftikhar Ali, PharmD, MPhil, MPH. Pharmacy Unit, Paraplegic Centre, Hayatabad, Peshawar, Pakistan.

Objective: To determine causative uropathogens and their antibiotic susceptibility pattern among Type-2 diabetics (T2D) with good and suboptimal glycemic control.

Methods: A hospital based cross-sectional study was carried out in Peshawar from April-October, 2019. Four hundred consecutive T2D patients with symptomatic UTI or showing numerous pus cells on routine urinary examination attending outpatient clinic were included. As per the guidelines of the Clinical and Laboratory Standards Institute (CLSI), the urine samples collected were checked for identification of uropathogen by culture. Disc diffusion method was used to determined antimicrobial susceptibility.

Results: Of the total (n=400) T2D patients, 205 (51.25%) showed microbial growth. Mean age of patients with UTI was 63.26 ±12.30 years. About two-third (63.9%) of the patients were females. Mean HbA1c was 8.80±2.20%. The frequency of patients with UTI was noticeably greater in the suboptimal glycemic control group 178(86.3%) compared to good control glycemic patients 27(13.7%). Significant mean difference in glycemic levels were observed (HbA1c = 5.86±0.48 and HbA1c = 9.25±2.02, respectively, < 0.001). E. coli was the predominant pathogen isolated 120(71%), followed by Klebsiella pneumonia Spp (K. pn) 35(17.1%), Pseudomonas auregonosa (P. aeruginosa) 14(6.83%), Enterococcus 12 (5.85%) and Candida Spp were 2(0.98%). Both gram positive and negative-bacteria were highly susceptible to imipenem, meropenem, fosfomycin and nitrofurantoin.

Conclusion: The frequency of UTI in diabetics was higher in female in comparison to male, and was significantly greater in the suboptimal glycemic control group. E. coli was the most typical isolate followed by K. pn. Imipenem, meropenem, fosfomycin and nitrofurantoin had high susceptibility profile against the isolated pathogens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12669/pjms.36.7.2881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674886PMC
November 2020

Immunity and amyloid beta, total tau and neurofilament light chain: Findings from a community-based cohort study.

Alzheimers Dement 2021 03 20;17(3):446-456. Epub 2020 Nov 20.

Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.

Introduction: We investigated how components of immunity relate to biomarkers of Alzheimer's disease (AD) in plasma and explored the influence of AD genetic risk factors in the population-based Rotterdam Study.

Methods: In 7397 persons, we calculated the granulocyte-to-lymphocyte ratio (GLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). In 3615 of these persons, plasma amyloid-beta (Aβ)42 and Aβ40 were measured. Next, we constructed an overall genetic risk score (GRS) based on genome-wide significant variants, both including and excluding APOE ε4.

Results: All innate immunity phenotypes were related to higher Aβ, most strongly with a doubling in GLR leading to a 1.9% higher Aβ42 (95% confidence interval [95% CI] 0.4 to 3.3%) and 3.2% higher Aβ40 (95% CI 2.0 to 4.3%). Higher AD GRS including APOE ε4 was associated with higher immunity markers.

Discussion: Higher levels of immunity markers were associated with higher Aβ in plasma. Participants with a higher genetic predisposition to AD had higher immunity markers, where these effects were mainly driven by APOE ε4.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alz.12212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048997PMC
March 2021

A Comparison of Prostate Cancer Detection between Visual Estimation (Cognitive Registration) and Image Fusion (Software Registration) Targeted Transperineal Prostate Biopsy.

J Urol 2021 Apr 18;205(4):1075-1081. Epub 2020 Nov 18.

Imperial Prostate, Division of Surgery, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, United Kingdom.

Purpose: We compared clinically significant prostate cancer detection by visual estimation and image fusion targeted transperineal prostate biopsy.

Materials And Methods: This multicenter study included patients with multiparametric magnetic resonance imaging lesions undergoing visual estimation or image fusion targeted transperineal biopsy (April 2017-March 2020). Propensity score matching was performed using demographics (age and ethnicity), clinical features (prostate specific antigen, prostate volume, prostate specific antigen density and digital rectal examination), multiparametric magnetic resonance imaging variables (number of lesions, PI-RADS® score, index lesion diameter, whether the lesion was diffuse and radiological T stage) and biopsy factors (number of cores, operator experience and anesthetic type). Matched groups were compared overall and by operator grade, PI-RADS score, lesion multiplicity, prostate volume and anesthetic type using targeted-only and targeted plus systematic histology. Multiple clinically significant prostate cancer thresholds were evaluated (primary: Gleason ≥3+4).

Results: A total of 1,071 patients with a median age of 67.3 years (IQR 61.3-72.4), median prostate specific antigen of 7.5 ng/ml (IQR 5.3-11.2) and 1,430 total lesions underwent targeted-only biopsies (visual estimation: 372 patients, 494 lesions; image fusion: 699 patients, 936 lesions). A total of 770 patients with a median age of 67.4 years (IQR 61-72.1), median prostate specific antigen of 7.1 ng/ml (IQR 5.2-10.6) and 919 total lesions underwent targeted plus systematic biopsies (visual estimation: 271 patients, 322 lesions; image fusion: 499 patients, 597 lesions). Matched comparisons demonstrated no overall difference in clinically significant prostate cancer detection between visual estimation and image fusion (primary: targeted-only 54% vs 57.4%, p=0.302; targeted plus systematic 51.2% vs 58.2%, p=0.123). Senior urologists had significantly higher detection rates using image fusion (primary: targeted-only 45.4% vs 63.7%, p=0.001; targeted plus systematic 39.4% vs 64.5%, p <0.001).

Conclusions: We found no overall difference in clinically significant prostate cancer detection, although image fusion may be superior in experienced hands.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JU.0000000000001476DOI Listing
April 2021

Indigenous Tocopherol Improves Tolerance of Oilseed Rape to Cadmium Stress.

Front Plant Sci 2020 23;11:547133. Epub 2020 Oct 23.

Department of Environmental Sciences and Engineering, Government College University, Faisalabad, Pakistan.

Two oilseed rape genotypes (Jiu-Er-13XI and Zheyou-50), differing in seed oil content, were subjected to cadmium (Cd) stress in hydroponic experiment. Genotypic differences were observed in terms of tolerance to Cd exposure. Cd treatment negatively affected both genotypes, but the effects were more devastating in Jiu-Er-13XI (low seed oil content) than in Zheyou-50 (high seed oil content). Jiu-Er-13XI accumulated more reactive oxygen species (ROS), which destroyed chloroplast structure and decreased photosynthetic pigments, than Zheyou-50. Total fatty acids, especially 18:2 and 18:3, severely decreased as suggested by increase in MDA content. Roots and shoots of Jiu-Er-13XI plants accumulated more Cd content, while less amount of tocopherol (Toc) was observed under Cd stress, than Zheyou-50. Conversely, Zheyou-50 was less affected by Cd stress than its counterpart. It accumulated comparatively less amount of Cd in roots and shoots, along with reduced accumulation of malondialdehyde (MDA) and ROS under Cd stress, than Jiu-Er-13XI. Further, the level of Toc, especially α-Tocopherol, was much higher in Zheyou-50 than in Jiu-Er-13XI, which was also supported by high expression of Toc biosynthesis genes in Zheyou-50 during early hours. Toc not only restricted the absorption of Cd by roots and its translocation to shoot but also scavenged the ROS generated during oxidative stresses. The low level of MDA shows that polyunsaturated fatty acids in chloroplast membranes remained intact. In the present study the tolerance of Zheyou-50 to Cd stress, over Jiu-Er-13XI, is attributed to the activities of Toc. This study shows that plants with high seed oil content are tolerant to Cd stress due to high production of Toc.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpls.2020.547133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7644955PMC
October 2020

Continuous renal replacement therapy with the addition of CytoSorb cartridge in critically ill patients with COVID-19 plus acute kidney injury: A case-series.

Artif Organs 2021 May 26;45(5):E101-E112. Epub 2020 Dec 26.

Critical Care Department, King Saud Medical City, Riyadh, Saudi Arabia.

Our aim was to investigate continuous renal replacement therapy (CRRT) with CytoSorb cartridge for patients with life-threatening COVID-19 plus acute kidney injury (AKI), sepsis, acute respiratory distress syndrome (ARDS), and cytokine release syndrome (CRS). Of 492 COVID-19 patients admitted to our intensive care unit (ICU), 50 had AKI necessitating CRRT (10.16%) and were enrolled in the study. Upon ICU admission, all had AKI, ARDS, septic shock, and CRS. In addition to CRRT with CytoSorb, all received ARDS-net ventilation, prone positioning, plus empiric ribavirin, interferon beta-1b, antibiotics, hydrocortisone, and prophylactic anticoagulation. We retrospectively analyzed inflammatory biomarkers, oxygenation, organ function, duration of mechanical ventilation, ICU length-of-stay, and mortality on day-28 post-ICU admission. Patients were 49.64 ± 8.90 years old (78% male) with body mass index of 26.70 ± 2.76 kg/m . On ICU admission, mean Acute Physiology and Chronic Health Evaluation (APACHE) II was 22.52 ± 1.1. Sequential Organ Function Assessment (SOFA) score was 9.36 ± 2.068 and the ratio of partial arterial pressure of oxygen to fractional inspired concentration of oxygen (PaO /FiO ) was 117.46 ± 36.92. Duration of mechanical ventilation was 17.38 ± 7.39 days, ICU length-of-stay was 20.70 ± 8.83 days, and mortality 28 days post-ICU admission was 30%. Nonsurvivors had higher levels of inflammatory biomarkers, and more unresolved shock, ARDS, AKI, and pulmonary emboli (8% vs. 4%, P < .05) compared to survivors. After 2 ± 1 CRRT sessions with CytoSorb, survivors had decreased SOFA scores, lactate dehydrogenase, ferritin, D-dimers, C-reactive protein, and interleukin-6; and increased PaO /FiO ratios, and lymphocyte counts (all P < .05). Receiver-operator-curve analysis showed that posttherapy values of interleukin-6 (cutoff point >620 pg/mL) predicted in-hospital mortality for critically ill COVID-19 patients (area-under-the-curve: 0.87, 95% CI: 0.81-0.93; P = .001). No side effects of therapy were recorded. In this retrospective case-series, CRRT with the CytoSorb cartridge provided a safe rescue therapy in life-threatening COVID-19 with associated AKI, ARDS, sepsis, and hyperinflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aor.13864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753655PMC
May 2021

Residual Lung Injury in Patients Recovering From COVID-19 Critical Illness: A Prospective Longitudinal Point-of-Care Lung Ultrasound Study.

J Ultrasound Med 2021 Sep 13;40(9):1823-1838. Epub 2020 Nov 13.

Department of Emergency Medicine, St. Francis Hospital, Columbus, Georgia, USA.

Scarce data exist regarding the natural history of lung lesions detected on ultrasound in those who survive severe COVID-19 pneumonia.

Objective: We performed a prospective analysis of point-of-care ultrasound (POCUS) findings in critically ill COVID-19 patients during and after hospitalization.

Methods: We enrolled 171 COVID-19 intensive care unit patients. POCUS of the lungs was performed with phased array (2-4 MHz), convex (2-6 MHz) and linear (10-15 MHz) transducers, scanning 12 lung areas. Chest computed tomography angiography was performed to exclude suspected pulmonary embolism. Survivors were clinically and sonographically evaluated during a 4 month period for evidence of residual lung injury. Chest computed tomography angiography and echocardiography were used to exclude pulmonary hypertension (PH) and chest high-resolution-computed-tomography to exclude interstitial lung disease (ILD) in symptomatic survivors.

Results: Cox regression analysis showed that lymphocytopenia (hazard ratio [HR]: 0.88, 95% confidence intervals [CI]: 0.68-0.96, p = .048), increased lactate (HR: 1.17, 95% CI: 0.94-1.46, p = 0.049), and D-dimers (HR: 1.21, 95% CI: 1.03-1.44, p = .03) were mortality predictors. Non-survivors had increased incidence of pulmonary abnormalities (B-lines, pleural line irregularities, and consolidations) compared to survivors (p < .05). During follow-up, POCUS with clinical and laboratory parameters integrated in the semi-quantitative Riyadh-Residual-Lung-Injury scale had sensitivity of 0.82 (95% CI: 0.76-0.89) and specificity of 0.91 (95% CI: 0.94-0.95) in predicting ILD. The prevalence of PH and ILD (non-specific-interstitial-pneumonia) was 7% and 11.8%, respectively.

Conclusion: POCUS showed ability to monitor the evolution of severe COVID-19 pneumonia after hospital discharge, supporting its integration in clinical predictive models of residual lung injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jum.15563DOI Listing
September 2021

Tempol (4-hydroxy tempo) protects mice from cisplatin-induced acute kidney injury modulation of expression of aquaporins and kidney injury molecule-1.

Drug Chem Toxicol 2020 Oct 20:1-9. Epub 2020 Oct 20.

Molecular Toxicology Laboratory, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi, India.

Tempol (4-hydroxy tempo), a pleiotropic antioxidant is reported to afford protection against cisplatin (CP)-induced nephrotoxicity. However, molecular mechanisms of action of tempol in improving the renal function in CP-induced nephrotoxicity are not fully understood. We investigated the attenuating effect of tempol against CP-induced alterations in kidney injury molecule-1 (KIM-1) and aquaporins (AQPs) in mice. Tempol (100 mg/kg, ) pretreatment with CP (20 mg/kg ) showed restoration in renal function markers including electrolytes. CP treatment upregulated mRNA expression of KIM-1 and downregulated AQP and arginine vasopressin (AVP) expression which was attenuated by tempol. Immunoblotting analysis revealed that CP-induced alterations in KIM-1 and AQP expression were restored by tempol. Immunofluorocense study also showed restorative effect of tempol on the expression of AQP2 in CP-treated mice. In conclusion, this study provides experimental evidence that tempol resolved urinary concentration defect by the restoration of AQP, AVP and KIM-1 levels indicating a potential use of tempol in ameliorating the AKI in cancer patients under the treatment with CP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/01480545.2020.1831011DOI Listing
October 2020

Association of lysophosphatidic acids with cerebrospinal fluid biomarkers and progression to Alzheimer's disease.

Alzheimers Res Ther 2020 10 2;12(1):124. Epub 2020 Oct 2.

Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.

Background: Lysophosphatidic acids (LPAs) are bioactive signaling phospholipids that have been implicated in Alzheimer's disease (AD). It is largely unknown whether LPAs are associated with AD pathology and progression from mild cognitive impairment (MCI) to AD.

Methods: The current study was performed on cerebrospinal fluid (CSF) and plasma samples of 182 MCI patients from two independent cohorts. We profiled LPA-derived metabolites using liquid chromatography-mass spectrometry. We evaluated the association of LPAs with CSF biomarkers of AD, Aβ-42, p-tau, and total tau levels overall and stratified by APOE genotype and with MCI to AD progression.

Results: Five LPAs (C16:0, C16:1, C22:4, C22:6, and isomer-LPA C22:5) showed significant positive association with CSF biomarkers of AD, Aβ-42, p-tau, and total tau, while LPA C14:0 and C20:1 associated only with Aβ-42 and alkyl-LPA C18:1, and LPA C20:1 associated with tau pathology biomarkers. Association of cyclic-LPA C16:0 and two LPAs (C20:4, C22:4) with Aβ-42 levels was found only in APOE ε4 carriers. Furthermore, LPA C16:0 and C16:1 also showed association with MCI to AD dementia progression, but results did not replicate in an independent cohort.

Conclusions: Our findings provide evidence that LPAs may contribute to early AD pathogenesis. Future studies are needed to determine whether LPAs play a role in upstream of AD pathology or are downstream markers of neurodegeneration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13195-020-00680-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532619PMC
October 2020

Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults.

Nat Commun 2020 09 22;11(1):4796. Epub 2020 Sep 22.

Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.

Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-18367-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508833PMC
September 2020

Prion protein codon 129 polymorphism in mild cognitive impairment and dementia: the Rotterdam Study.

Brain Commun 2020 20;2(1):fcaa030. Epub 2020 Mar 20.

Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, Netherlands.

Creutzfeldt-Jakob disease is a rare, fatal, neurodegenerative disease caused by the accumulation of abnormally folded prion proteins. The common polymorphism at codon 129 (methionine/valine) in the prion protein () gene is the most important determinant of genetic susceptibility. Homozygotes of either allele have a higher risk of sporadic Creutzfeldt-Jakob disease. Various studies suggest that this polymorphism is also involved in other forms of dementia. We studied the association between the codon 129 polymorphism of the gene and mild cognitive impairment in 3605 participants from the Rotterdam Study using logistic regression analyses. Subsequently, we studied the association between this polymorphism and incident dementia, including Alzheimer's disease, in 11 070 participants using Cox proportional hazard models. Analyses were adjusted for age and sex. We found the prevalence of mild cognitive impairment to be higher for carriers of the methionine/methionine genotype (odds ratio, 1.40; 95% confidence interval, 1.11-1.78; =0.005) as well as for carriers of the valine/valine genotype (odds ratio, 1.37; 95% confidence interval, 0.96-1.97; =0.08). The codon 129 polymorphism was not associated with the risk of incident dementia or Alzheimer's disease. In conclusion, we found a statistically significant higher prevalence of mild cognitive impairment in carriers of the methionine/methionine genotype in the codon 129 polymorphism of the gene within this population-based study. No associations were found between the codon 129 polymorphism and dementia or Alzheimer's disease in the general population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/braincomms/fcaa030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425338PMC
March 2020

Circulating metabolites are associated with brain atrophy and white matter hyperintensities.

Alzheimers Dement 2021 02 4;17(2):205-214. Epub 2020 Sep 4.

Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.

Introduction: Our aim was to study whether systemic metabolites are associated with magnetic resonance imaging (MRI) measures of brain and hippocampal atrophy and white matter hyperintensities (WMH).

Methods: We studied associations of 143 plasma-based metabolites with MRI measures of brain and hippocampal atrophy and WMH in three independent cohorts (n = 3962). We meta-analyzed the results of linear regression analyses to determine the association of metabolites with MRI measures.

Results: Higher glucose levels and lower levels of three small high density lipoprotein (HDL) particles were associated with brain atrophy. Higher glucose levels were associated with WMH.

Discussion: Glucose levels were associated with brain atrophy and WMH, and small HDL particle levels were associated with brain atrophy. Circulating metabolites may aid in developing future intervention trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/alz.12180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984157PMC
February 2021

Co-infection of SARS-CoV-2 and in a young man with idiopathic non-cystic bronchiectasis and vitamin D deficiency.

Respir Med Case Rep 2020 28;31:101203. Epub 2020 Aug 28.

Critical Care Department, King Saud Medical City, Riyadh, Saudi Arabia.

This is the first reported case, to our knowledge, of co-infection of and SARS-CoV-2 in a young patient with underlying idiopathic bronchiectasis and vitamin D deficiency that was treated successfully with a combination therapeutic regime integrating doxycycline, empiric therapies for COVID-19, vitamin D supplementation, and supportive ICU care. Large prospective studies are required to investigate further the role of co-infections in COVID-19 patients with bronchiectasis. Randomized control trials should examine the putative beneficial role of vitamin D supplementation in patients with COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rmcr.2020.101203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452825PMC
August 2020

Calmodulin-binding transcription activator (CAMTA) genes family: Genome-wide survey and phylogenetic analysis in flax (Linum usitatissimum).

PLoS One 2020 23;15(7):e0236454. Epub 2020 Jul 23.

Department of Food Science and Technology, Zhejiang University of Technology, Hangzhou, Zhejiang, China.

Flax (Linum usitatissimum) is a member of family linaceae with annual growth habit. It is included among those crops which were domesticated very early and has been used in development related studies as a model plant. In plants, Calmodulin-binding transcription activators (CAMTAs) comprise a unique set of Calmodulin-binding proteins. To elucidate the transport mechanism of secondary metabolites in flax, a genome-based study on these transporters was performed. The current investigation identified nine CAMTAs proteins, classified into three categories during phylogenetic analysis. Each group had significant evolutionary role as illustrated by the conservation of gene structures, protein domains and motif organizations over the distinctive phylogenetic classes. GO annotation suggested a link to sequence-specific DNA and protein binding, response to low temperature and transcription regulation by RNA polymerase II. The existence of different hormonal and stress responsive cis-regulatory elements in promotor region may directly correlate with the variation of their transcripts. MicroRNA target analysis revealed that various groups of miRNA families targeted the LuCAMTAs genes. Identification of CAMTA genes, miRNA studies and phylogenetic analysis may open avenues to uncover the underlying functional mechanism of this important family of genes in flax.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236454PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377914PMC
September 2020

Drought-induced alterations in photosynthetic, ultrastructural and biochemical traits of contrasting sugarcane genotypes.

PLoS One 2020 8;15(7):e0235845. Epub 2020 Jul 8.

College of Agronomy and Biotechnology, China Agricultural University, Beijing, China.

Drought is an important factor which limits growth of sugarcane. To elucidate the physiological and biochemical mechanisms of tolerance, a pot experiment was conducted at Sugarcane Research Institute, Kaiyuan, China. Two genotypes (Yuetang 93-159-sensitive and Yunzhe 05-51-tolerant), were subjected to three treatments; 70±5% (control), 50±5% (moderate drought) and 30±5% (severe drought) of soil field capacity. The results demonstrated that drought induced considerable decline in morpho-physiological, biochemical and anatomical parameters of both genotypes, with more pronounced detrimental effects on Yuetang 93-159 than on Yunzhe 05-51. Yunzhe 05-51 exhibited more tolerance by showing higher dry biomass, photosynthesis and antioxidant enzyme activities. Compared with Yuetang 93-159, Yunzhe 05-51 exhibited higher soluble sugar, soluble protein and proline contents under stress. Yunzhe 05-51 illustrated comparatively well-composed chloroplast structure under drought stress. It is concluded that the tolerance of Yunzhe 05-51 was attributed to improved antioxidant activities, osmolyte accumulation and enhanced photosynthesis. These findings may provide valuable information for future studies on molecular mechanism of tolerance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235845PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343164PMC
September 2020

CDH6 and HAGH protein levels in plasma associate with Alzheimer's disease in APOE ε4 carriers.

Sci Rep 2020 05 19;10(1):8233. Epub 2020 May 19.

Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.

Many Alzheimer's disease (AD) genes including Apolipoprotein E (APOE) are found to be expressed in blood-derived macrophages and thus may alter blood protein levels. We measured 91 neuro-proteins in plasma from 316 participants of the Rotterdam Study (incident AD = 161) using Proximity Extension Ligation assay. We studied the association of plasma proteins with AD in the overall sample and stratified by APOE. Findings from the Rotterdam study were replicated in 186 AD patients of the BioFINDER study. We further evaluated the correlation of these protein biomarkers with total tau (t-tau), phosphorylated tau (p-tau) and amyloid-beta (Aβ) 42 levels in cerebrospinal fluid (CSF) in the Amsterdam Dementia Cohort (N = 441). Finally, we conducted a genome-wide association study (GWAS) to identify the genetic variants determining the blood levels of AD-associated proteins. Plasma levels of the proteins, CDH6 (β = 0.638, P = 3.33 × 10) and HAGH (β = 0.481, P = 7.20 × 10), were significantly elevated in APOE ε4 carrier AD patients. The findings in the Rotterdam Study were replicated in the BioFINDER study for both CDH6 (β = 1.365, P = 3.97 × 10) and HAGH proteins (β = 0.506, P = 9.31 × 10) when comparing cases and controls in APOE ε4 carriers. In the CSF, CDH6 levels were positively correlated with t-tau and p-tau in the total sample as well as in APOE ε4 stratum (P < 1 × 10). The HAGH protein was not detected in CSF. GWAS of plasma CDH6 protein levels showed significant association with a cis-regulatory locus (rs111283466, P = 1.92 × 10). CDH6 protein is implicated in cell adhesion and synaptogenesis while HAGH protein is related to the oxidative stress pathway. Our findings suggest that these pathways may be altered during presymptomatic AD and that CDH6 and HAGH may be new blood-based biomarkers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-65038-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237496PMC
May 2020

Exome Sequencing Analysis Identifies Rare Variants in and That Are Associated With Shorter Telomere Length.

Front Genet 2020 30;11:337. Epub 2020 Apr 30.

Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, Netherlands.

Telomeres are important for maintaining genomic stability. Telomere length has been associated with aging, disease, and mortality and is highly heritable (∼82%). In this study, we aimed to identify rare genetic variants associated with telomere length using whole-exome sequence data. We studied 1,303 participants of the Erasmus Rucphen Family (ERF) study, 1,259 of the Rotterdam Study (RS), and 674 of the British Heart Foundation Family Heart Study (BHF-FHS). We conducted two analyses, first we analyzed the family-based ERF study and used the RS and BHF-FHS for replication. Second, we combined the summary data of the three studies in a meta-analysis. Telomere length was measured by quantitative polymerase chain reaction in blood. We identified nine rare variants significantly associated with telomere length (-value < 1.42 × 10, minor allele frequency of 0.2-0.5%) in the ERF study. Eight of these variants (in , , , , , and ) were located on chromosome 11q22.3 that contains , a gene involved in telomere maintenance. Although we were unable to replicate the variants in the RS and BHF-FHS (-value ≥ 0.21), segregation analysis showed that all variants segregate with shorter telomere length in a family. In the meta-analysis of all studies, a nominally significant association with LTL was observed with a rare variant in (- = 1.48 × 10), which has previously been associated with age. Additionally, a novel rare variant in the known locus showed suggestive evidence for association (-value = 1.18 × 10) with LTL. To conclude, we identified novel rare variants associated with telomere length. Larger samples size are needed to confirm these findings and to identify additional variants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2020.00337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204400PMC
April 2020

Molecular interactions of vinclozolin metabolites with human estrogen receptors 1GWR-α and 1QKM and androgen receptor 2AM9-β: Implication for endocrine disruption.

Toxicol Mech Methods 2020 Jun 14;30(5):370-377. Epub 2020 Apr 14.

Molecular Toxicology Laboratory, Department of Medical Elementology & Toxicology, Jamia Hamdard (Hamdard University), New Delhi, India.

Vinclozolin (VCZ) is a widely used antifungal agent with capability to enter into the human food chain. VCZ metabolizes into seven metabolites M1-M7. Several studies have shown its effects on reprotoxicity. However, there is limited information available on the interaction of VCZ metabolites with nuclear receptors. studies aimed at identifying interaction of endocrine disruptor with nuclear receptors serve a prescreening framework in risk assessment. We studied interactive potential of VCZ and its metabolites with human estrogen (ER) and androgen receptor (AR) using molecular docking method. Binding potential of VCZ and its metabolites with estrogen receptors 1GWR-α, 1QKM and androgen receptor 2AM9-β was checked by using Schrodinger Maestro 10.5. Estradiol (E2), a natural ligand of ER and AR was taken as a reference. VCZ and its metabolites showed higher or similar binding efficiency on interaction with target proteins when compared with E2. VCZ and its metabolites also exhibited agonistic effect against 1GWR-α, 1QKM and 2AM9-β with strong binding potential to them. Some VCZ metabolites such as M4 and M5 showed higher binding potencies with 1GWR-α, 1QKM and 2AM9-β than E2. Toxicity data of VCZ is well endowed. However, endocrine disrupting potential of VCZ via nuclear receptor mediated pathway is less understood. This study revealing that not only VCZ but its metabolites have potential to interact with 1GWR-α, 1QKM and 2AM9-β offers a platform for further exploration of VCZ in this direction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15376516.2020.1747123DOI Listing
June 2020

Efficient 1-Hour Technetium-99 m Pyrophosphate Imaging Protocol for the Diagnosis of Transthyretin Cardiac Amyloidosis.

Circ Cardiovasc Imaging 2020 02 17;13(2):e010249. Epub 2020 Feb 17.

Division of Cardiology, Heart and Vascular Institute, University of Pittsburgh Medical Center, PA (A.M., S.B, S.A., R.N., W.F., A.B., T.C.W., E.S., P.S.).

Background: Technetium-99 m pyrophosphate protocols for transthyretin cardiac amyloidosis diagnosis have variably used 1- and 3-hour imaging time points. We investigated whether imaging at 1 hour with superior efficiency had comparable diagnostic accuracy as 3-hour imaging.

Methods: This is a registry analysis of patients with suspected transthyretin cardiac amyloidosis referred for technetium-99 m pyrophosphate at a single tertiary center from June 2015 through January 2019. Patients underwent planar and single-photon emission computed tomography (SPECT) imaging at 1 and 3 hours. A positive Tc-99m pyrophosphate study was defined by the presence of diffuse myocardial tracer uptake on SPECT. For planar imaging, visual semiquantitative (grades 0-3, ≥2 considered positive) and quantitative heart to contralateral ratios (≥1.5 considered positive) were used.

Results: Two hundred thirty-three patients (69% men; median age, 77 [69-83] years) underwent the study protocol. There were 60 (25.8%) patients with diffuse myocardial uptake, 1 (0.4%) with regional uptake, and 172 (73.8%) with no myocardial uptake. Results of SPECT were identical at 1 and 3 hours. Planar imaging at 1 hour had 98% sensitivity and 96% specificity. Planar grade 0 uptake or heart to contralateral ratio ≤1.2 and planar grade 3 uptake or heart to contralateral ratio ≥2.0 were always associated with negative and positive SPECT, respectively. For planar grades 1 and 2 uptake and heart to contralateral ratio 1.3 to 1.9, SPECT was needed to make a diagnosis. No patient with light-chain cardiac amyloidosis had positive SPECT.

Conclusions: An efficient 1-hour technetium-99 m pyrophosphate protocol had comparable diagnostic performance to a 3-hour protocol.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCIMAGING.119.010249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7032611PMC
February 2020

Mechanisms of left ventricular dyssynchrony: A multinational SPECT study of patients with bundle branch block.

J Nucl Cardiol 2021 Jun 14;28(3):1140-1150. Epub 2020 Feb 14.

Division of Cardiology and The Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Background: To better understand the mechanisms of left ventricular (LV) mechanical dyssynchrony (LVMD), we explored the relative contributions of QRS duration (QRSd), LV ejection fraction (EF), volumes and scar to LVMD measured by gated single-photon emission tomography in a population of consecutive patients with left bundle branch block (LBBB) and right bundle branch block (RBBB) compared to controls.

Methods: Myocardial perfusion imaging studies of 275 LBBB and 83 RBBB patients from three centers were analyzed. LVMD was defined as an abnormal phase bandwidth or phase standard deviation. Hospital and gender-specific normal values were obtained from 172 controls.

Results: The prevalence of LVMD was 85 and 40% in LBBB and RBBB, respectively. Ejection fraction, scar severity, and LBBB morphology independently explained 70% of variance seen in PhaseBW. Ejection fraction had the highest area under the curve (AUC 0.918) in the receiver operating characteristics analysis of LVMD with an optimal cut-off of 47% (sensitivity 73% and specificity 98%). Notably, QRSd was not predictive.

Conclusion: LV mechanical dysfunction plays a greater role than conduction abnormality in the genesis of LVMD, a finding that is intriguing in the context of contemporary literature which suggests that QRSd is the parameter that is most predictive of CRT response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12350-020-02054-yDOI Listing
June 2021

Effective governance for management of invasive alien plants: evidence from the perspective of forest and wildlife officers in Sri Lanka.

PeerJ 2020 6;8:e8343. Epub 2020 Jan 6.

School of Economics and Management, Beijing Forestry University, Beijing, China.

Invasive alien plants (IAPs) are a significant cause of socio-ecological change in Sri Lanka. Many studies have focused on the ecological dimensions of this problem, but few have addressed sociological factors such as the knowledge and perceptions of individuals and groups tasked with addressing IAPs. This study investigates how IAP issues are understood and perceived by professional forest and wildlife officers in Sri Lanka. The data analyzed were gathered using a questionnaire that covered three themes: the respondents' ability to identify IAPs, the impacts of IAPs and the threats they pose, and knowledge regarding control and mitigation. The questionnaire was completed by 186 field officers, and the resulting descriptive statistics and a probit regression analysis were used to analyze the data. The results show that almost all of the participating forest and wildlife officers were aware of the problems associated with IAPs but more than 75% of them lacked an accurate understanding of scientific means for controlling them and control policies established by the government of Sri Lanka. Generally, wildlife officers had a better understanding than forest officers. In addition, the analysis shows that officers' knowledge and perceptions of IAPs were positively correlated with their level of education and position within the organization. The analysis points to several recommendations for Sri Lankan officials when designing and implementing comprehensive policies and professional programs, particularly for lower-level field officers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.8343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6951289PMC
January 2020
-->