The aims of this study were to characterize and investigate antimicrobial susceptibility and presence of integrons in 161 Aeromonas spp. isolated from ornamental freshwater fish farming environment, ...apparently healthy and diseased fish. Phylogenetic analyses of the gyrB gene sequences identified Aeromonas veronii as the most abundant species (75.8%) followed by Aeromonashydrophila (9.3%), Aeromonas caviae (5%), Aeromonas jandaei (4.3%), Aeromonas dhakensis (3.7%), Aeromonas sobria (0.6%), Aeromonas media (0.6%), and Aeromonas popoffii (0.6%). Susceptibility to thirteen antimicrobials was determined and antimicrobial resistance frequencies were: amoxicillin (92.5%), enrofloxacin (67.1%), nalidixic acid (63.4%), erythromycin (26.1%), tetracycline (23.6%), imipenem (18%), trimethoprim-sulfamethoxazole (16.8%), and gentamicin (16.8%). Multi-drug resistance (MDR) was widespread among the isolates (51.6%, 83/161) with 51.6% (63/122) A. veronii isolates being MDR. In addition, 68.3% of isolates had multiple antibiotic resistance (MAR) indexes higher than 0.2, suggesting that they originated from a high-risk source of contamination where antimicrobials are often used. In all, 21.7% isolates carried class 1 integrons, with 97.1% having gene cassettes, while there were 12 isolates carrying class 2 integron gene cassettes. Our findings highlight that the aquatic environment and ornamental fish act as reservoirs of multidrug resistant Aeromonas spp. and underline the need for a judicious use of antimicrobials and timely surveillance of antimicrobial resistance (AMR) in aquaculture.
Objective
Epilepsy develops in 70 to 90% of children with tuberous sclerosis complex (TSC) and is often resistant to medication. Recently, the concept of preventive antiepileptic treatment to modify ...the natural history of epilepsy has been proposed. EPISTOP was a clinical trial designed to compare preventive versus conventional antiepileptic treatment in TSC infants.
Methods
In this multicenter study, 94 infants with TSC without seizure history were followed with monthly video electroencephalography (EEG), and received vigabatrin either as conventional antiepileptic treatment, started after the first electrographic or clinical seizure, or preventively when epileptiform EEG activity before seizures was detected. At 6 sites, subjects were randomly allocated to treatment in a 1:1 ratio in a randomized controlled trial (RCT). At 4 sites, treatment allocation was fixed; this was denoted an open‐label trial (OLT). Subjects were followed until 2 years of age. The primary endpoint was the time to first clinical seizure.
Results
In 54 subjects, epileptiform EEG abnormalities were identified before seizures. Twenty‐seven were included in the RCT and 27 in the OLT. The time to the first clinical seizure was significantly longer with preventive than conventional treatment RCT: 364 days (95% confidence interval CI = 223–535) vs 124 days (95% CI = 33–149); OLT: 426 days (95% CI = 258–628) vs 106 days (95% CI = 11–149). At 24 months, our pooled analysis showed preventive treatment reduced the risk of clinical seizures (odds ratio OR = 0.21, p = 0.032), drug‐resistant epilepsy (OR = 0.23, p = 0.022), and infantile spasms (OR = 0, p < 0.001). No adverse events related to preventive treatment were noted.
Interpretation
Preventive treatment with vigabatrin was safe and modified the natural history of seizures in TSC, reducing the risk and severity of epilepsy. ANN NEUROL 2021;89:304–314
Enhancing the sustainability of food packaging (FP) is challenging due to the conflicting environmental and functional requirements, even though it leads to many negative environmental impacts over ...different life cycle phases. Sustainable FP aims to strike a balance in fulfilling protection, facilitation of handling, and communication functions while minimizing the environmental impacts and economic costs. Yet, there is a lack of holistic frameworks that support sustainable FP design decision-making processes based on life cycle thinking. Thus, the objective of this study is to develop a generalizable framework combining life cycle thinking with functional analysis for systematically and holistically comparing sustainable packaging design options, considering environmental, economic, and consumer preference dimensions. The proposed approach was applied to a rigid plastic packaging case study involving ketchup bottles. Kano's theory and Quality Function Deployment (QFD) were used to identify the user requirements, applicable design features, and prioritisation. Then, conjoint analysis, life cycle analysis (LCA), and analytical cost estimation were used to estimate the functional satisfaction, environmental impact, and costs incurred respectively. Finally, the values obtained for three criteria were aggregated using Fuzzy Analytical Hierarchy Process (AHP) and the overall sustainability of the design options was compared. The results show that both material quantity, type, and shape majorly influence the functional, environmental, and economic impacts. There is a disparity between the options with the highest functional satisfaction and the lowest environmental impacts respectively. The aggregated score indicates that an option currently available in the market has the highest performance, and yet there are other options with better environmental performance. However, even after the scores are aggregated, the inputs of packaging experts maybe necessary to successfully balance the sustainability requirements with the user expectations. The findings of this research, which proposes a systematic and holistic design process, can support packaging designers, industry decision-makers, and policy planners in enhancing the sustainability of FP.
Display omitted
•A holistic decision support framework based on life cycle thinking is needed for sustainable packaging design.•Environmental and economic criteria need to be aggregated with consumer preference in optimizing packaging designs.•QFD was combined with life cycle thinking in performance evaluation of design options.•Material quantity is the dominant parameter that contributes to overall environmental impacts of packaging.•Occupied volume has a critical impact on the transportation-related environmental impacts.
Objective:
The goal is to evaluate avelumab, an anti-PD-L1 monoclonal immunoglobulin G antibody labeled with zirconium-89 in human PD-L1-expressing cancer cells and mouse xenografts for clinical ...translation.
Methods:
89ZrZr-DFO-PD-L1 monoclonal antibody (mAb) was synthesized using avelumab conjugated to desferrioxamine. In vitro binding studies and biodistribution studies were performed with PD-L1+MDA-MB231 cells and MDA-MB231 xenograft mouse models, respectively. Biodistributions were determined at 1, 2, 3, 5, and 7 days post coinjection of 89ZrZr-DFO-PD-L1 mAb without or with unlabeled avelumab (10, 20, 40, and 400 µg).
Results:
89ZrZr-DFO-PD-L1 mAb exhibited high affinity (Kd ∼ 0.3 nM) and detected moderate PD-L1 expression levels in MDA-MB231 cells. The spleen and lymph nodes exhibited the highest 89ZrZr-DFO-PD-L1 mAb uptakes in all time points, while MDA-MB231 tumor uptakes were lower but highly retained. In the unlabeled avelumab dose escalation studies, spleen tissue–muscle ratios decreased in a dose-dependent manner indicating specific 89ZrZr-DFO-PD-L1 mAb binding to PD-L1. In contrast, lymph node and tumor tissue–muscle ratios increased 4- to 5-fold at 20 and 40 µg avelumab doses.
Conclusions:
89ZrZr-DFO-PD-L1 mAb exhibited specific and high affinity for PD-L1 in vitro and had target tissue uptakes correlating with PD-L1 expression levels in vivo. 89ZrZr-DFO-PD-L1 mAb uptake in PD-L1+tumors increased with escalating doses of avelumab.
GWAS have identified hundreds of height-associated loci. However, determining causal mechanisms is challenging, especially since height-relevant tissues (e.g. growth plates) are difficult to study. ...To uncover mechanisms by which height GWAS variants function, we performed epigenetic profiling of murine femoral growth plates. The profiled open chromatin regions recapitulate known chondrocyte and skeletal biology, are enriched at height GWAS loci, particularly near differentially expressed growth plate genes, and enriched for binding motifs of transcription factors with roles in chondrocyte biology. At specific loci, our analyses identified compelling mechanisms for GWAS variants. For example, at
, we identified a candidate causal variant (rs9920291) overlapping an open chromatin region. Reporter assays demonstrated that rs9920291 shows allelic regulatory activity, and CRISPR/Cas9 targeting of human chondrocytes demonstrates that the region regulates
expression. Thus, integrating biologically relevant epigenetic information (here, from growth plates) with genetic association results can identify biological mechanisms important for human growth.
Despite the growth of geriatric home health services, little is known about the mental health needs of geriatric patients seen in their homes. The authors report the distribution, correlates, and ...treatment status of DSM-IV major depression in a random sample of elderly patients receiving home health care for medical or surgical problems.
Geriatric patients newly admitted to a large, traditional visiting nurse agency were sampled on a weekly basis over a period of 2 years. The 539 patients ranged in age from 65 to 102 years; 351 (65%) were women, and 81 (15%) were nonwhite. The Structured Clinical Interview for DSM-IV Axis I Disorders was used to interview patients and informants. The authors reviewed the results of these interviews plus the patients' medical charts to generate a best-estimate DSM-IV psychiatric diagnosis.
The patients had substantial medical burden and disability. According to DSM-IV criteria, 73 (13.5%) of the 539 patients were diagnosed with major depression. Most of these patients (N=52, 71%) were experiencing their first episode of depression, and the episode had lasted for more than 2 months in most patients (N=57, 78%). Major depression was significantly associated with medical morbidity, instrumental activities of daily living disability, reported pain, and a past history of depression but not with cognitive function or sociodemographic factors. Only 16 (22%) of the depressed patients were receiving antidepressant treatment, and none was receiving psychotherapy. Five (31%) of the 16 patients receiving antidepressants were prescribed subtherapeutic doses, and two (18%) of the 11 who were prescribed appropriate doses reported not complying with their antidepressant treatment.
Geriatric major depression is twice as common in patients receiving home care as in those receiving primary care. Most depressions in patients receiving home care are untreated. The poor medical and functional status of these patients and the complex organizational structure of home health care pose a challenge for determining safe and effective strategies for treating depressed elderly home care patients.
The goal of this study was the characterisation of indigenous lactic acid bacteria (LAB) and yeasts isolated from nine white pickled (BG) and nine fresh soft (ZG) artisanal cheeses collected in ...Serbia and Croatia. While LAB were present in all of the cheeses collected, yeasts were found in all BG cheeses but only in three ZG cheese samples. High LAB and yeast species diversity was determined (average H′L=0.4 and H′Y=0.8, respectively). The predominant LAB species in white pickled (BG) cheeses were Lactococcus lactis, Lactobacillus plantarum, and Leuconostoc mesenteroides, while in fresh soft (ZG) cheeses the most dominant LAB species were L. lactis, Enterococcus faecalis, and Leuconostoc pseudomesenteroides. Among the 20 yeast species found, Debaryomyces hansenii, Candida zeylanoides, and Torulaspora delbrueckii were found to be predominant in BG cheeses, while Yarrowia lipolytica was predominant in ZG cheeses. The characterisation of metabolic and technological potentials revealed that 53.4% of LAB isolates produced antimicrobial compounds, 44.3% of LAB strains showed proteolytic activity, while most of the yeast species possessed either lipolytic or proteolytic activity. In conclusion, the results obtained in this study showed that the composition of LAB and yeast populations in white pickled and fresh soft cheeses is region specific. The knowledge gained in this study could eventually be used to select region specific LAB and yeast strains for the production of white pickled and fresh soft artisanal cheeses with geographically specific origins under controlled conditions.
•Indigenous microbiota of 18 artisanal cheeses from Serbia and Croatia was determined.•LAB and yeast species were identified by using traditional and molecular methods.•High diversity of LAB and yeast populations were found.•Impact on starter culture development for traditional cheeses with defined properties•Implementation in controlled production of artisanal cheeses with geographical origin
Gene regulation in the human genome is controlled by distal enhancers that activate specific nearby promoters
. A proposed model for this specificity is that promoters have sequence-encoded ...preferences for certain enhancers, for example, mediated by interacting sets of transcription factors or cofactors
. This 'biochemical compatibility' model has been supported by observations at individual human promoters and by genome-wide measurements in Drosophila
. However, the degree to which human enhancers and promoters are intrinsically compatible has not yet been systematically measured, and how their activities combine to control RNA expression remains unclear. Here we design a high-throughput reporter assay called enhancer × promoter self-transcribing active regulatory region sequencing (ExP STARR-seq) and applied it to examine the combinatorial compatibilities of 1,000 enhancer and 1,000 promoter sequences in human K562 cells. We identify simple rules for enhancer-promoter compatibility, whereby most enhancers activate all promoters by similar amounts, and intrinsic enhancer and promoter activities multiplicatively combine to determine RNA output (R
= 0.82). In addition, two classes of enhancers and promoters show subtle preferential effects. Promoters of housekeeping genes contain built-in activating motifs for factors such as GABPA and YY1, which decrease the responsiveness of promoters to distal enhancers. Promoters of variably expressed genes lack these motifs and show stronger responsiveness to enhancers. Together, this systematic assessment of enhancer-promoter compatibility suggests a multiplicative model tuned by enhancer and promoter class to control gene transcription in the human genome.
P048 A young girl with myocardial infarction Janagan, Shalini; Gunathilaka, M. P. M. L; Rajagopala, Lavanya ...
Rheumatology (Oxford, England),
04/2022, Letnik:
61, Številka:
Supplement_1
Journal Article
Recenzirano
Odprti dostop
Abstract
Background/Aims
Takayasu arteritis is a chronic granulomatous inflammatory disease of the aorta and its major branches. It is commonly seen in young women but has been reported in children ...as young as 6 months. Acute myocardial infarction due to coronary artery involvement is a rare presentation in Takayasu’s arteritis.
Methods
A previously healthy 13-year-old girl presented with a history of five episodes of short lasting exertional tightening type chest pain with adrenergic symptoms over a week which was relieved by rest. She didn't have any history of shortness of breath, limb claudication or constitutional symptoms. However, on two of the occasions she felt faint. She denied any recreational drug use. There was no family history of cardiovascular disease, connective tissue diseases or sudden cardiac death. On examination she was of average build with no peripheral stigmata of connective tissue diseases or hypercholesterolemia. Apart from a tachycardia of 110 bpm, her cardiovascular examination was normal. There was no BP difference between the arms and no audible bruits. All her peripheral pulses were felt.
Results
Her ECG showed ST segment depressions in V1-V5. High sensitivity Troponin I was strongly positive. An urgent CT coronary angiogram revealed aortitis involving the ascending and arch of the aorta extending to the left subclavian artery with both coronary arteries showing smooth short segment narrowing at the origin. Doppler USS abdomen showed wall thickening of proximal and mid abdominal aorta. Blood investigations showed a leucocytosis of 14,100/µl and thrombocytosis of 532000/µl. Her ESR was raised at 31 mm/hr and CRP was 5 mg/l. While further awaiting investigations she was started on treatment as for non-ST elevation myocardial infarction according to standard guidelines. Screening for tuberculosis and VDRL were negative . A CT aortic angiogram showed wall thickening involving the aortic root, coronary arteries, ascending aorta and the abdominal aorta with involvement of the origins of coeliac axis and the superior mesenteric artery. Appearance were suggestive of Takayasu arteritis Type v. She was pulsed with intravenous methylprednisolone 30 mg/kg for 3 days followed by oral prednisolone 2 mg/kg. As a steroid sparing agent methotrexate was added. Despite treatment, while in hospital she developed chest pain with ECG showing new onset ST elevation in aVR. An urgent coronary angiogram done showed severe LMCA disease for which stenting was done.
At this stage Tocilizumab was initiated. A year later she remains well controlled in terms of her disease activity.
Conclusion
Though rare, Takayasu’s arteritis should be considered in any adolescent female presenting with ischemic type symptoms and positive inflammatory response. High index of suspicion can lead to early imaging and aggressive immunosuppression that will reduce the morbidity and mortality of this disease.
Disclosure
S. Janagan: None. M.P.M.L. Gunathilaka: None. L. Rajagopala: None. J.D. Jagoda: None.
High-coverage whole-genome sequence studies have so far focused on a limited number of geographically restricted populations, or been targeted at specific diseases, such as cancer. Nevertheless, the ...availability of high-resolution genomic data has led to the development of new methodologies for inferring population history and refuelled the debate on the mutation rate in humans. Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long- and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record, and admixture between AMHs and Neanderthals predating the main Eurasian expansion, our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75,000 years ago.
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