Results of the United States multicenter prospective study evaluating the Zenith fenestrated endovascular graft for treatment of juxtarenal abdominal aortic aneurysms

OBJECTIVE: This study reports the results of a prospective, multicenter trial designed to evaluate the safety and effectiveness of the Zenith fenestrated endovascular graft (Cook Medical, Bloomington, Ind) for treatment of juxtarenal abdominal aortic aneurysms (AAAs). METHODS: Sixty-seven patients with juxtarenal AAAs were prospectively enrolled in 14 centers in the United States from 2005 to 2012. Custom-made fenestrated stent grafts were designed with one to three fenestrations on the basis of analysis of computed tomography data sets. Renal alignment was performed with balloon-expandable stents. Follow-up included clinical examination, laboratory studies, mesenteric-renal duplex ultrasound, abdominal radiography, and computed tomography imaging at hospital discharge and at 1 month, 6 months, and 12 months and yearly thereafter up to 5 years. RESULTS: There were 54 male and 13 female patients with a mean age of 74 ± 8 years enrolled. Mean aneurysm diameter was 60 ± 10 mm. A total of 178 visceral arteries required incorporation with small fenestrations in 118, scallops in 51, and large fenestrations in nine. Of these, all 118 small fenestrations (100%), eight of the scallops (16%), and one of the large fenestrations (11%) were aligned by stents. Technical success was 100%. There was one postoperative death within 30 days (1.5%). Mean length of hospital stay was 3.3 ± 2.1 days. No aneurysm ruptures or conversions were noted during a mean follow-up of 37 ± 17 months (range, 3-65 months). Two patients (3%) had migration ≥ 10 mm with no endoleak, both due to cranial progression of aortic disease. Of a total of 129 renal arteries targeted by a fenestration, there were four (3%) renal artery occlusions and 12 (9%) stenoses. Fifteen patients (22%) required secondary interventions for renal artery stenosis/occlusion in 11 patients, type II endoleak in three patients, and type I endoleak in one patient. At 5 years, patient survival was 91% ± 4%, and freedom from major adverse events was 79% ± 6%; primary and secondary patency of targeted renal arteries was 81% ± 5% and 97% ± 2%, freedom from renal function deterioration was 91% ± 5%, and freedom from secondary interventions was 63% ± 9%. CONCLUSIONS: This prospective study demonstrates that endovascular repair of juxtarenal AAAs with the Zenith fenestrated AAA stent graft is safe and effective. Mortality and morbidity are low in properly selected patients treated in centers with experience in these procedures

Evaluating the In Vitro Activity of Depsidones from Usnea subfloridana Stirton as Key Enzymes Involved in Inflammation and Gout

Background: Traditionally, Usnea genus has significant uses in the treatment of swelling and tumors in Africa and Asia. The aim of the present study was to investigate the chemical constituents present in the acetone extract (AE) of Usnea subfloridana Stirton and also to evaluate their anti-inflammatory and anti-gout effects. Methods: Isolation and characterization of secondary metabolites from AE were evaluated by chromatography and spectral studies. Anti-inflammatory activities were assessed through cyclooxygenase (COX1 and COX2) and 5-lipooxygenase (5-LOX) enzyme inhibition assays, while anti-gout effects were evaluated by xanthine oxidase (XO) inhibition assay. Results: The existence of five known depsidones, identified as galbinic acid (1), conprotocetraricacid (2), constictic acid (3), salazinic acid (4), and lobaric acid (5), were exposed by chemical investigation of AE and confirmed by spectral data. Using in vitro enzyme inhibition assays, it was noticed that all the isolates showed dose-dependent activity against all the tested enzymes. Mainly, compounds 2 and 5 showed better inhibition efficiency on COX2 enzyme with the IC50of 7.17±1.07 and 7.01±0.94 nM, respectively, than the reference drug indomethacin (7.3±0.65nM). Furthermore, all isolates exhibited potent inhibition effects on the XO enzyme. Conclusion: The results indicated that U. subfloridana can be a favorable natural source for thetreatment of inflammation and gout. Compounds 2 and 5 were responsible for these biologicalactions by regulating pro-inflammatory enzymes, namely COXs, 5-LOX, and XO

Genome-wide transcriptome analysis and physiological variation modulates gene regulatory networks acclimating salinity tolerance in chickpea

Salinity is a major abiotic stress that is a global threat to crop production, including chickpea. This study focused on understanding the complex molecular mechanisms underlying salinity tolerance using comparative transcriptome analysis of tolerant (ICCV 10, JG 11) and sensitive (DCP 92-3, Pusa 256) chickpea genotypes in control and salt-stressed environments. A total of 530 million reads were generated from root samples of four genotypes using Illumina HiSeq-2500. A total of 21,698 differentially expressed genes (DEGs) were identified, of which 11,456 and 10,242 were up- and down-regulated, respectively, in comparative analysis. These DEGs were associated with crucial metabolic pathways, including hormone signaling, photosynthesis, lipid and carbohydrate metabolism, and cell wall biogenesis. Gene ontology (GO) examination revealed an enrichment of transcripts involved in salinity response. A total of 4257 differentially expressed GO terms were categorized into 64 functional groups; of which, GO terms like, integral component of membrane, organelle, and cellular anatomical entity were highly represented in tolerant genotypes under salt stress. Significant up-regulation of transcripts encoding potassium transporter family HAK/KUP proteins, MIP/aquaporin protein family, NADH dehydrogenase, pectinesterase, and PP2C family proteins occurred under salt stress. The tolerant lines (ICCV 10 and JG 11) engaged highly efficient machinery in response to elevated salt stress, especially for signal transduction, transport and influx of K+ ions, and osmotic homeostasis. The overall study highlights the role of potential candidate genes and their regulatory networks which can be utilized in breeding salt tolerant chickpea cultivars

A comprehensive analysis of Trehalose-6-phosphate synthase (TPS) gene for salinity tolerance in chickpea (Cicer arietinum L.)

Soil salinity affects various crop cultivation but legumes are the most sensitive to salinity. Osmotic stress is the first stage of salinity stress caused by excess salts in the soil on plants which adversely affects the growth instantly. The Trehalose-6-phosphate synthase (TPS) genes play a key role in the regulation of abiotic stresses resistance from the high expression of different isoform. Selected genotypes were evaluated to estimate for salt tolerance as well as genetic variability at morphological and molecular level. Allelic variations were identified in some of the selected genotypes for the TPS gene. A comprehensive analysis of the TPS gene from selected genotypes was conducted. Presence of significant genetic variability among the genotypes was found for salinity tolerance. This is the first report of allelic variation of TPS gene from chickpea and results indicates that the SNPs present in these conserved regions may contribute largely to functional distinction. The nucleotide sequence analysis suggests that the TPS gene sequences were found to be conserved among the genotypes. Some selected genotypes were evaluated to estimate for salt tolerance as well as for comparative analysis of physiological, molecular and allelic variability for salt responsive gene Trehalose-6-Phosphate Synthase through sequence similarity. Allelic variations were identified in some selected genotypes for the TPS gene. It is found that Pusa362, Pusa1103, and IG5856 are the most salt-tolerant lines and the results indicates that the identified genotypes can be used as a reliable donor for the chickpea improvement programs for salinity tolerance

Environmental Exposure and Leptospirosis, Peru

Human infection by leptospires has highly variable clinical manifestations, which range from subclinical infection to fulminant disease. We conducted a population-based, cross-sectional seroepidemiologic study in Peru to determine potential relationships of environmental context to human exposure to Leptospira and disease associated with seroconversion. Three areas were studied: a flooded, urban slum in the Peruvian Amazon city of Iquitos; rural, peri-Iquitos villages; and a desert shantytown near Lima. Seroprevalence in Belen was 28% (182/650); in rural areas, 17% (52/316); and in a desert shantytown, 0.7% (1/150). Leptospira-infected peridomestic rats were found in all locales. In Belen, 20 (12.4%) of 161 patients seroconverted between dry and wet seasons (an incidence rate of 288/1,000). Seroconversion was associated with history of febrile illness; severe leptospirosis was not seen. Human exposure to Leptospira in the Iquitos region is high, likely related both to the ubiquity of leptospires in the environment and human behavior conducive to transmission from infected zoonotic sources

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

Infrared-Image Classification Using Hidden Markov Trees

Images of three-dimensional targets are characterized by the target subcomponents visible from a particular target-sensor orientation (target pose), with the image often changing quickly with variable pose. We define a class as a set of contiguous target-sensor orientations over which the associated target image is relatively stationary with aspect, and therefore each target is in general characterized by multiple classes. Our feature parser employs a distinct set of Wiener filters for each class of images, to identify the presence of target subcomponents. The Wiener filters are designed using a KarhunenLoeve expansion. The statistical relationships between the different target subcomponents are modeled via a hidden Markov tree (HMT). The HMT classifier is discussed and example results are presented for forward-looking-infrared (FLIR) imagery of several vehicles. Classification performance is compared with that of several other competing classifiers