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Spontaneous coronary artery dissection (SCAD) is a potential precipitant of myocardial infarction and sudden death for which the etiology is poorly understood. Mendelian vascular and connective tissue disorders underlying thoracic aortic disease (TAD), have been reported in ~5% of individuals with SCAD. We therefore hypothesized that patients with TAD are at elevated risk for SCAD. We queried registries enrolling patients with TAD to define the incidence of SCAD. Of 7568 individuals enrolled, 11 (0.15%) were found to have SCAD. Of the sequenced cases (9/11), pathogenic variants were identified (N = 9), including COL3A1 (N = 3), FBN1 (N = 2), TGFBR2 (N = 2), TGFBR1 (N = 1), and PRKG1 (N = 1). Individuals with SCAD had an increased frequency of iliac artery dissection (25.0% vs. 5.1%, p = 0.047). The prevalence of SCAD among individuals with TAD is low. The identification of pathogenic variants in genes previously described in individuals with SCAD, particularly those underlying vascular Ehlers-Danlos, Marfan syndrome, and Loeys-Dietz syndrome, is consistent with prior reports from clinical SCAD series. Further research is needed to identify specific genetic influences on SCAD risk., (© 2022 Wiley Periodicals LLC.)

Background: A two-phase 'respiratory symptoms' mass media campaign was conducted in 2016 and 2017 in England raising awareness of cough and worsening shortness of breath as symptoms warranting a general practitioner (GP) visit., Method: A prospectively planned pre-post evaluation was done using routinely collected data on 15 metrics, including GP attendance, GP referral, emergency presentations, cancers diagnosed (five metrics), cancer stage, investigations (two metrics), outpatient attendances, inpatient admissions, major lung resections and 1-year survival. The primary analysis compared 2015 with 2017. Trends in metrics over the whole period were also considered. The effects of the campaign on awareness of lung cancer symptoms were evaluated using bespoke surveys., Results: There were small favourable statistically significant and clinically important changes over 2 years in 11 of the 15 metrics measured, including a 2.11% (95% confidence interval 1.02-3.20, p < 0.001) improvement in the percentage of lung cancers diagnosed at an early stage. However, these changes were not accompanied by increases in GP attendances. Furthermore, the time trends showed a gradual change in the metrics rather than steep changes occurring during or after the campaigns., Conclusion: There were small positive changes in most metrics relating to lung cancer diagnosis after this campaign. However, the pattern over time challenges whether the improvements are wholly attributable to the campaign. Given the importance of education on cancer in its own right, raising awareness of symptoms should remain important. However further research is needed to maximise the effect on health outcomes., (© 2021. The Author(s).)

Objective: A regional 'Be Clear on Cancer' (BCoC) campaign developed by Public Health England aimed to promote public awareness of key abdominal cancer symptoms in people aged 50 years and over., Methods: Data were analysed for metrics at different stages in the patient care pathway including public awareness, GP attendance and referrals, to cancer diagnosis., Results: There was significantly higher recognition of the BCoC abdominal campaign in the campaign region compared to the control area (Post Campaign/Control, n = 401/406; 35% vs. 24%, p < 0.05). The campaign significantly improved knowledge of 'bloating' as a symptom (p = 0.03) compared to pre-campaign levels. GP attendances for abdominal symptoms increased significantly by 5.8% (p = 0. 03), although the actual increase per practice was small (average 16.8 visits per week in 2016 to 17.7 in 2017). Urgent GP referrals for suspected abdominal cancer increased by 7.6%, compared to a non-significant change (0.05%) in the control area. For specific abdominal cancers, the number diagnosed were similar to or higher than the median in the campaign area but not in the control area in people aged 50 and over: colorectal (additional n = 61 cancers), pancreatic (additional n = 102) and stomach cancers (additional n = 17)., Conclusions: This campaign had a modest impact on public awareness of abdominal cancer symptoms, GP attendances and cancers diagnosed., (© 2021 The Authors. European Journal of Cancer Care published by John Wiley & Sons Ltd.)

Objective: While rare variants in the COL5A1 gene have been associated with classical Ehlers-Danlos syndrome and rarely with arterial dissections, recurrent variants in COL5A1 underlying a systemic arteriopathy have not been described. Monogenic forms of multifocal fibromuscular dysplasia (mFMD) have not been previously defined. Approach and Results: We studied 4 independent probands with the COL5A1 pathogenic variant c.1540G>A, p.(Gly514Ser) who presented with arterial aneurysms, dissections, tortuosity, and mFMD affecting multiple arteries. Arterial medial fibroplasia and smooth muscle cell disorganization were confirmed histologically. The COL5A1 c.1540G>A variant is predicted to be pathogenic in silico and absent in gnomAD. The c.1540G>A variant is on a shared 160.1 kb haplotype with 0.4% frequency in Europeans. Furthermore, exome sequencing data from a cohort of 264 individuals with mFMD were examined for COL5A1 variants. In this mFMD cohort, COL5A1 c.1540G>A and 6 additional relatively rare COL5A1 variants predicted to be deleterious in silico were identified and were associated with arterial dissections ( P =0.005)., Conclusions: COL5A1 c.1540G>A is the first recurring variant recognized to be associated with arterial dissections and mFMD. This variant presents with a phenotype reminiscent of vascular Ehlers-Danlos syndrome. A shared haplotype among probands supports the existence of a common founder. Relatively rare COL5A1 genetic variants predicted to be deleterious by in silico analysis were identified in ≈2.7% of mFMD cases, and as they were enriched in patients with arterial dissections, may act as disease modifiers. Molecular testing for COL5A1 should be considered in patients with a phenotype overlapping with vascular Ehlers-Danlos syndrome and mFMD.

Background: Renal artery aneurysms (RAAs) may reflect a systemic dysplastic arteriopathy, independent of a recognized connective tissue disease. It is hypothesized that RAAs are associated with an increased risk of intracranial aneurysms (IcAs). The objective of this study was to better define the association of IcAs in women with RAAs., Methods: Women aged 20 to 60 years who presented with RAAs at the University of Michigan from 2001 to 2016 were included in the study. Their clinical status and radiologic images were retrospectively reviewed, with particular attention directed to the prevalence of IcAs. Phenotypic characteristics predictive of associated cerebrovascular lesions were assessed using various statistical analyses, including binomial logistic regression., Results: Among 83 women with RAAs, the average age at the time of RAA detection was 45.3 ± 9.9 years (range, 20-60 years). Hypertension affected 56 (67.5%) patients and poorly controlled hypertension prompted imaging for suspected renal arterial disease in 12 (14.5%) patients. Multifocal fibromuscular dysplasia occurred in 12 (14.8%) of patients, and unifocal stenosis affected 7 (8.4%) patients. Imaging of the intracranial vasculature (n = 31) documented 12 aneurysms in 9 women, with the cavernous internal carotid artery being the most commonly affected artery. Among the study's patients, 20 (24.1%) had an "at-risk disorder for IcA formation," although the frequency of relevant "at-risk disorders" in those with and without IcAs was not statistically different (P = 0.21). Rupture risk defined by PHASES score was less than 1% for 10 IcAs, but 2 IcAs carried a 2.4% and 7.2% rupture risk, respectively, over a 5-year time period. Surgical management was pursued in 6 (50%) of the study's IcAs., Conclusions: Coexisting RAAs and IcAs may reflect a systemic arteriopathy. IcAs appear to occur with greater frequency in women with RAAs than the general population. This observation warrants prospective investigation as to the clinical appropriateness and relevance of cerebrovascular imaging in women with RAAs. Furthermore, this study's findings prompt further investigation of the underlying pathogenesis of what appears to be a broader and more complex arterial disease than previously recognized., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We present here the complete genomes of 18 phages that infect Paenibacillus larvae, the causative agent of American foulbrood in honeybees. The phages were isolated between 2014 and 2016 as part of an undergraduate phage discovery course at Brigham Young University. The phages were isolated primarily from bee debris and lysogens.

Background: Best practice recommendations are lacking. Thus far, literature has described pharmacist-led DOAC monitoring., Objective: The purpose of this study is to describe a DOAC monitoring program involving pharmacy students., Methods: This was an observational analysis of a quality improvement initiative. A clinical pharmacist preceptor identified clinic patients taking DOACs by running a report using the electronic medical record. Pharmacy students conducted chart reviews, called pharmacies for 6-month refill histories, and interviewed and educated patients. Findings were communicated to the care team and interventions were performed as applicable with the preceptor., Results: Of 90 patients included, the mean age was 63 years, 54% were female, and 65.6% were black or African American. Rivaroxaban and apixaban were used most commonly. Sixty-two percent of DOACs were prescribed for atrial fibrillation/flutter, while 32.2% for venous thromboembolism. The mean MPR was 77.1%, with 27.7% of patients having an MPR ≤60%. Of the 136 student-led interventions, 25.2% involved medication access, 24.4% adherence education, 20.7% processing refills, 14.8% laboratory monitoring recommendations, 8.9% switching or recommending switching to another anticoagulant, and 4.4% stopping a nonsteroidal anti-inflammatory drug or aspirin., Conclusion: Pharmacy students can help to ensure medication safety and effective use of DOACs.

We present here the complete genomes of eight phages that infect Paenibacillus larvae , the causative agent of American foulbrood in honeybees. Phage PBL1c was originally isolated in 1984 from a P. larvae lysogen, while the remaining phages were isolated in 2014 from bee debris, honeycomb, and lysogens from three states in the USA., (Copyright © 2018 Walker et al.)

While successful magnetic tumor targeting of iron oxide nanoparticles has been achieved in a number of models, the rapid blood clearance of magnetically suitable particles by the reticuloendothelial system (RES) limits their availability for targeting. This work aimed to develop a long-circulating magnetic iron oxide nanoparticle (MNP) platform capable of sustained tumor exposure via the circulation and, thus, potentially enhanced magnetic tumor targeting. Aminated, cross-linked starch (DN) and aminosilane (A) coated MNPs were successfully modified with 5 kDa (A5, D5) or 20 kDa (A20, D20) polyethylene glycol (PEG) chains using simple N-Hydroxysuccinimide (NHS) chemistry and characterized. Identical PEG-weight analogues between platforms (A5 & D5, A20 & D20) were similar in size (140-190 nm) and relative PEG labeling (1.5% of surface amines - A5/D5, 0.4% - A20/D20), with all PEG-MNPs possessing magnetization properties suitable for magnetic targeting. Candidate PEG-MNPs were studied in RES simulations in vitro to predict long-circulating character. D5 and D20 performed best showing sustained size stability in cell culture medium at 37 °C and 7 (D20) to 10 (D5) fold less uptake in RAW264.7 macrophages when compared to previously targeted, unmodified starch MNPs (D). Observations in vitro were validated in vivo, with D5 (7.29 h) and D20 (11.75 h) showing much longer half-lives than D (0.12 h). Improved plasma stability enhanced tumor MNP exposure 100 (D5) to 150 (D20) fold as measured by plasma AUC(0-∞). Sustained tumor exposure over 24 h was visually confirmed in a 9L-glioma rat model (12 mg Fe/kg) using magnetic resonance imaging (MRI). Findings indicate that a polyethylene glycol modified, cross-linked starch-coated MNP is a promising platform for enhanced magnetic tumor targeting, warranting further study in tumor models., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

To establish a role for insulin-like growth factor-1 (IGF-1) in bladder cancer susceptibility, we tested the effect of p-cresidine, a potent bladder carcinogen, in transgenic (TG) mice with human IGF-1 expression in the bladder driven by the bovine keratin 5 promoter (referred to as BK5.IGF-1 TG mice). Indomethacin was also tested to determine if the cyclooxygenase (COX) pathway is a target for bladder cancer prevention in this model. Thirty-three female BK5.IGF-1 TG mice and 29 female nontransgenic littermates were randomized to the following treatments: (1) AIN-76A diet; (2) AIN-76A diet with 0.5% p-cresidine; or (3) AIN-76A diet with 0.5% p-cresidine + 0.00075% indomethacin. BK5.IGF-1 TG mice, with twofold greater total serum IGF-1 than nontransgenic mice, exhibited greatly increased susceptibility to p-cresidine-induced bladder tumors compared to nontransgenic mice. The most common type of bladder tumor in the BK5.IGF-1 TG mice was transitional cell carcinoma, which is the predominant type of bladder cancer observed in developed countries. Indomethacin inhibition of bladder tumor development in BK5.IGF-1 TG mice was not statistically significant. These results present further evidence for the role of IGF-1 in bladder cancer progression. In addition, these transgenic mice provide a useful model for studying the role of the IGF-1 pathway in bladder carcinogenesis and its prevention.

The 1990s were a period of considerable economic and social instability in Kazakhstan. The current study documents information on the growth performance of children living in Kazalinsk district in the far west of Kazakhstan over this turbulent period. Using anthropometric data of children, from random samples collected in 1992, 1994 and 2000, we investigate changes in body size of 4.0-4.9-year-old children over the 8-year-study period. Between 1992 and 2000, there was no statistically significant change in body size of 4.0-4.9-year-old boys, but 4.0-4.9-year-old girls became significantly smaller. This may have resulted from the prolonged period of economic instability in Kazakhstan. Furthermore, using detailed dietary intake data collected in 1994, evidence is presented to support a suggestion that the different responses to economic hardship, evidenced in the achieved body size of boys and girls, may have been influenced by gender-discrimination in household food allocation.

Studies of biomarkers of putative breast carcinogens, such as DNA adducts, have been limited by the difficulty in obtaining representative ductal epithelial cells (DECs) from breast tissue. In this feasibility study, we sought to ascertain if exfoliated DECs in breast milk could be a source of DNA for biomarker studies. Specimens (n = 38) were collected over 24 h from nursing women, and a questionnaire was administered. Cell pellets were isolated by repeated centrifugation and washing. Pellets were resuspended and incubated for 2 h, with glass adherence used to remove monocytes, resulting in an enrichment of DECs of >80%. Nonadherent cells were removed, washed, and homogenized for DNA isolation. Accurate DNA quantification was performed by 32P-postlabeling of normal nucleotides under conditions of excess ATP. Although there was wide variability in the amounts of DNA recovered, DNA yield was significantly associated with the number of weeks postpartum (P < 0.01), with optimal yield between 6 and 8 weeks after birth. There were no significant associations (P < 0.05) between the number of cells recovered and milk volume, method of collection, or the number of samples in a 24-h period per individual. This study demonstrates that breast milk can be used as a source of DECs for biomarker studies of gene-environment interaction and that sufficient DNA can be recovered to evaluate carcinogen-DNA adducts and to perform genotyping assays. Using this approach, exfoliated DECs may serve as a source of representative cells for studies of breast carcinogenesis and biomarkers of exposure, susceptibility, and effect.

Eight field trials were conducted in 1989 and 1990 in Georgia (USA) and Maryland (USA) to evaluate baits and baiting strategies for delivering oral rabies vaccines to raccoons (Procyon lotor). Bait packets consisting of corn meal and egg batter-based baits enclosed in plastic bags were placed at 1.0-m diameter, raked tracking stations and checked daily. Packets were well accepted by raccoons; they visited 31 to 44% of the tracking stations where they removed 69 to 90% of the packets within 4 to 5 days. All or nearly all baits were removed from plastic bags and less than 1% of the baits were found only partially eaten. No rejection of water-filled paraffin ampules in baits was observed. The use of an odor attractant on bait packets did not appear to enhance bait discovery when packets were placed on raccoon travel routes. An attractant did enhance discovery when baits were placed off-road in a simulated aerial baiting test. Nontarget species comprised 31 to 53% of all visits to the stations; they took 28 to 55% of the baits but did not appear to adversely affect bait availability for raccoons. A total of 2,300 baits, each containing a wax ampule holding 10 mg of a physiological marker (iophenoxic acid), were distributed at a rate of 82 baits/km2 on 2,800 ha of Sapelo Island, Georgia. Thirty-five (65%) of 54 raccoons collected following bait placement had eaten one or more baits as indicated by elevated levels of iodine in the blood serum.

Our experiences with omental and myocutaneous flaps for the closure of the lower abdomen, groin, and perineum are outlined. The relative advantages and disadvantages of the various flaps are discussed.

The duration and stereotypy (in terms of duration) of three actions, stand-overs (SO), generalbites (GB), And scruff-bites (SB), were measured during social play and agonistic interactions in infant eastern coyotes (Canis latrans). The rate of biting was also calculated. We found: (1) SO's and GB's lasted a significantly shorter time during play; (2) when performed during playful interactions, all three acts showed more stereotypy; (3) there was no significant difference between the rates of occurrence of biting during the two situations. A discussion of the 'exaggerated' nature of play behaviour is presented, particularly concerning the form of motor actions that are used during this activity.

The tensor fascia lata (TFL) muscle, together with the overlying skin of the anterolateral thigh, makes a reliable musculocutaneous unit. It can be lengthened safely by taking the fascia lata and the skin of the anterolateral mid and lower thigh to within 8 cm of the knee. The skin of the longer flap is supplied by large perforating musculocutaneous arteries, the terminal branches of the vascular pedicle of the muscle. The shorter flap can easily be transposed over the trochanteric area, while the larger flap will cover not only the trochanter but also the ischial and sacral areas. The flap serves equally well as a transposition, island, or free flap. The anatomical and vascular basis of the flap is presented, together with its application in 21 patients. Possible further applications of the flap, including anterior rotation, are discussed.

The transverse lumbosacral back flap is presented as a good one to use for coverage of sacral defects. Its reliability appears to be due to an axial pattern of its proximal portion, and to an uninterrupted subdermal vascular plexus across the midline of the back (supplying the terminal portion). A retrospective analysis of its use in 20 patients, over the last 3 years, suggests that when it is designed properly it can be most useful in the management of sacral pressure sores.

The tensor fascia lata muscle and its overlying skin provide a reliable myocutaneous unit containing a large amount of soft tissue for a free flap transfer. Its anatomy is outlined, and the operative technique for transfer is detailed in a case of chronic stasis ulcer of the lower leg.

Atypically located varices are frequently overlooked in the differential diagnosis of gastrointestinal bleeding in patients with portal hypertension. The circulatory changes associated with these lesions are described and their relation to diagnosis and treatment emphasized.