Coronary artery fistula; coronary computed topography – The diagnostic modality of choice

Coronary artery fistulae (CAF) are rare anomalies. They are vascular communications between the coronary arteries and other cardiac structures, either cardiac chambers or great vessels. There can be considerable variation in the course of a coronary artery fistula. We report a case of a coronary artery fistula between the left circumflex coronary artery and the right and left atria. CAF are often diagnosed by coronary angiogram, however with the advent of new technologies such as Coronary Computed Tomography Angiography (Coronary CTA) the course and communications of these fistulae can be delineated non-invasively and with greater accuracy

Association of Amyloid Pathology With Myelin Alteration in Preclinical Alzheimer Disease

IMPORTANCE: The accumulation of aggregated β-amyloid and tau proteins into plaques and tangles is a central feature of Alzheimer disease (AD). While plaque and tangle accumulation likely contributes to neuron and synapse loss, disease-related changes to oligodendrocytes and myelin are also suspected of playing a role in development of AD dementia. Still, to our knowledge, little is known about AD-related myelin changes, and even when present, they are often regarded as secondary to concomitant arteriosclerosis or related to aging. OBJECTIVE: To assess associations between hallmark AD pathology and novel quantitative neuroimaging markers while being sensitive to white matter myelin content. DESIGN, SETTING AND PARTICIPANTS: Magnetic resonance imaging was performed at an academic research neuroimaging center on a cohort of 71 cognitively asymptomatic adults enriched for AD risk. Lumbar punctures were performed and assayed for cerebrospinal fluid (CSF) biomarkers of AD pathology, including β-amyloid 42, total tau protein, phosphorylated tau 181, and soluble amyloid precursor protein. We measured whole-brain longitudinal and transverse relaxation rates as well as the myelin water fraction from each of these individuals. MAIN OUTCOMES AND MEASURES: Automated brain mapping algorithms and statistical models were used to evaluate the relationships between age, CSF biomarkers of AD pathology, and quantitative magnetic resonance imaging relaxometry measures, including the longitudinal and transverse relaxation rates and the myelin water fraction. RESULTS: The mean (SD) age for the 19 male participants and 52 female participants in the study was 61.6 (6.4) years. Widespread age-related changes to myelin were observed across the brain, particularly in late myelinating brain regions such as frontal white matter and the genu of the corpus callosum. Quantitative relaxometry measures were negatively associated with levels of CSF biomarkers across brain white matter and in areas preferentially affected in AD. Furthermore, significant age-by-biomarker interactions were observed between myelin water fraction and phosphorylated tau 181/β-amyloid 42, suggesting that phosphorylated tau 181/β-amyloid 42 levels modulate age-related changes in myelin water fraction. CONCLUSIONS AND RELEVANCE: These findings suggest amyloid pathologies significantly influence white matter and that these abnormalities may signify an early feature of the disease process. We expect that clarifying the nature of myelin damage in preclinical AD may be informative on the disease’s course and lead to new markers of efficacy for prevention and treatment trials

Need-based resource allocation: different need indicators, different results?

<p>Abstract</p> <p>Background</p> <p>A key policy objective in most publicly financed health care systems is to allocate resources according to need. Many jurisdictions implement this policy objective through need-based allocation models. To date, no gold standard exists for selecting need indicators. In the absence of a gold standard, sensitivity of the choice of need indicators is of concern. The primary objective of this study was to assess the consistency and plausibility of estimates of per capita relative need for health services across Canadian provinces based on different need indicators.</p> <p>Methods</p> <p>Using the 2000/2001 Canadian Community Health Survey, we estimated relative per capita need for general practitioner, specialist, and hospital services by province using two approaches that incorporated a different set of need indicators: (1) demographics (age and sex), and (2) demographics, socioeconomic status, and health status. For both approaches, we first fitted regression models to estimate standard utilization of each of three types of health services by indicators of need. We defined the standard as average levels of utilization by needs indicators in the national sample. Subsequently, we estimated expected per capita utilization of each type of health services in each province. We compared these estimates of per capita relative need with premature mortality in each province to check their face validity.</p> <p>Results</p> <p>Both approaches suggested that expected relative per capita need for three services vary across provinces. Different approaches, however, yielded different and inconsistent results. Moreover, provincial per capita relative need for the three health services did not always indicate the same direction of need suggested by premature mortality in each province. In particular, the two approaches suggested Newfoundland had less need than the Canadian average for all three services, but it had the highest premature mortality in Canada.</p> <p>Conclusion</p> <p>Substantial differences in need for health care may exist across Canadian provinces, but the direction and magnitude of differences depend on the need indicators used. Allocations from models using survey data lacked face validity for some provinces. These results call for the need to better understand the biases that may result from the use of survey data for resource allocation.</p

Lemierre's syndrome due to Klebsiella pneumoniae in a 63-year-old man with diabetes: a case report

<p>Abstract</p> <p>Introduction</p> <p>Lemierre's syndrome was originally documented to be caused by <it>Fusobacterium necrophorum</it>. It is a very rare condition with a prevalence of one to 14.4 instances per million. Its presentation is varied, not only in composition but also in the infecting organism. Treatment with anticoagulants has been controversial and applied only on a case-by-case basis.</p> <p>Case presentation</p> <p>A 63-year-old Saudi man who had had uncontrolled diabetes mellitus for 47 years presented to our facility with a five-day history of swelling on the right side of his neck and fever. The swelling progressively increased in size and was associated with pain, dysphagia, odynophagia, change of voice ('hot potato voice'), and reduced appetite. Abscess content culture and sensitivity testing revealed <it>Klebsiella pneumoniae</it>. However, blood culture results were repeatedly negative. The abscess was incised and drained without any complication. Our patient was treated with clindamycin and cefuroxime. Warfarin was also administered concurrently for six weeks, for an isolated internal jugular vein thrombosis (IJV), with complete resolution of the thrombus. Normoglycemia was achieved and our patient was discharged after complete wound healing and the return of his biochemical parameters to normal.</p> <p>Conclusions</p> <p>Only two cases of Lemierre's syndrome in patients with diabetes due to <it>K. pneumoniae </it>have been reported previously. A review of the literature suggested that an association exists between deep neck infections due to <it>K. pneumoniae </it>and diabetes mellitus. The reasons for this association are still not clear. This poses a question as to whether diabetes mellitus specifically predisposes these patients to infection with this organism. It is suggested that clinicians should consider infectious agents other than <it>F. necrophorum </it>in the causation of Lemierre's syndrome, especially in patients with diabetes.</p

SEIS: Insight's Seismic Experiment for Internal Structure of Mars.

By the end of 2018, 42 years after the landing of the two Viking seismometers on Mars, InSight will deploy onto Mars' surface the SEIS (Seismic Experiment for Internal Structure) instrument; a six-axes seismometer equipped with both a long-period three-axes Very Broad Band (VBB) instrument and a three-axes short-period (SP) instrument. These six sensors will cover a broad range of the seismic bandwidth, from 0.01&nbsp;Hz to 50&nbsp;Hz, with possible extension to longer periods. Data will be transmitted in the form of three continuous VBB components at 2 sample per second (sps), an estimation of the short period energy content from the SP at 1&nbsp;sps and a continuous compound VBB/SP vertical axis at 10&nbsp;sps. The continuous streams will be augmented by requested event data with sample rates from 20 to 100 sps. SEIS will improve upon the existing resolution of Viking's Mars seismic monitoring by a factor of ∼ 2500 at 1&nbsp;Hz and ∼ 200 000 at 0.1&nbsp;Hz. An additional major improvement is that, contrary to Viking, the seismometers will be deployed via a robotic arm directly onto Mars' surface and will be protected against temperature and wind by highly efficient thermal and wind shielding. Based on existing knowledge of Mars, it is reasonable to infer a moment magnitude detection threshold of M w ∼ 3 at 40 ∘ epicentral distance and a potential to detect several tens of quakes and about five impacts per year. In this paper, we first describe the science goals of the experiment and the rationale used to define its requirements. We then provide a detailed description of the hardware, from the sensors to the deployment system and associated performance, including transfer functions of the seismic sensors and temperature sensors. We conclude by describing the experiment ground segment, including data processing services, outreach and education networks and provide a description of the format to be used for future data distribution.Electronic supplementary materialThe online version of this article (10.1007/s11214-018-0574-6) contains supplementary material, which is available to authorized users

Strongly magnetized pulsars: explosive events and evolution

Well before the radio discovery of pulsars offered the first observational confirmation for their existence (Hewish et al., 1968), it had been suggested that neutron stars might be endowed with very strong magnetic fields of $10^{10}$-$10^{14}$G (Hoyle et al., 1964; Pacini, 1967). It is because of their magnetic fields that these otherwise small ed inert, cooling dead stars emit radio pulses and shine in various part of the electromagnetic spectrum. But the presence of a strong magnetic field has more subtle and sometimes dramatic consequences: In the last decades of observations indeed, evidence mounted that it is likely the magnetic field that makes of an isolated neutron star what it is among the different observational manifestations in which they come. The contribution of the magnetic field to the energy budget of the neutron star can be comparable or even exceed the available kinetic energy. The most magnetised neutron stars in particular, the magnetars, exhibit an amazing assortment of explosive events, underlining the importance of their magnetic field in their lives. In this chapter we review the recent observational and theoretical achievements, which not only confirmed the importance of the magnetic field in the evolution of neutron stars, but also provide a promising unification scheme for the different observational manifestations in which they appear. We focus on the role of their magnetic field as an energy source behind their persistent emission, but also its critical role in explosive events.Comment: Review commissioned for publication in the White Book of "NewCompStar" European COST Action MP1304, 43 pages, 8 figure

Ca2+/Calmodulin-Dependent Protein Kinase Kinase Is Not Involved in Hypothalamic AMP-Activated Protein Kinase Activation by Neuroglucopenia

Hypoglycemia and neuroglucopenia stimulate AMP-activated protein kinase (AMPK) activity in the hypothalamus and this plays an important role in the counterregulatory responses, i.e. increased food intake and secretion of glucagon, corticosterone and catecholamines. Several upstream kinases that activate AMPK have been identified including Ca2+/Calmodulin-dependent protein kinase kinase (CaMKK), which is highly expressed in neurons. However, the involvement of CaMKK in neuroglucopenia-induced activation of AMPK in the hypothalamus has not been tested. To determine whether neuroglucopenia-induced AMPK activation is mediated by CaMKK, we tested whether STO-609 (STO), a CaMKK inhibitor, would block the effects of 2-deoxy-D-glucose (2DG)-induced neuroglucopenia both ex vivo on brain sections and in vivo. Preincubation of rat brain sections with STO blocked KCl-induced α1 and α2-AMPK activation but did not affect AMPK activation by 2DG in the medio-basal hypothalamus. To confirm these findings in vivo, STO was pre-administrated intracerebroventricularly (ICV) in rats 30 min before 2DG ICV injection (40 µmol) to induce neuroglucopenia. 2DG-induced neuroglucopenia lead to a significant increase in glycemia and food intake compared to saline-injected control rats. ICV pre-administration of STO (5, 20 or 50 nmol) did not affect 2DG-induced hyperglycemia and food intake. Importantly, activation of hypothalamic α1 and α2-AMPK by 2DG was not affected by ICV pre-administration of STO. In conclusion, activation of hypothalamic AMPK by 2DG-induced neuroglucopenia is not mediated by CaMKK

Lifestyle factors and primary glioma and meningioma tumours in the Million Women Study cohort

Previous studies have reported inconsistent results on the effect of anthropometric and lifestyle factors on the risk of developing glioma or meningioma tumours. A prospective cohort of 1.3 million middle-aged women was used to examine these relationships. During 7.7 million women-years of follow-up, a total of 1563 women were diagnosed with a primary incident central nervous system tumour: 646 tumours were classified as glioma and 390 as meningioma. Our results show that height is related to the incidence of all central nervous system tumours with a risk of about 20% per 10 cm increase in height (relative risk=1.19, 95% CI=1.10–1.30 per 10 cm increase in height, P<0.001): the risks did not differ significantly between specified glioma and meningioma. Body mass index (BMI) was also related to central nervous system tumour incidence, with a risk of about 20% per 10 kg m−2 increase in BMI (relative risk=1.17, 95% CI=1.03–1.34 per 10 kg m−2 increase in BMI, P=0.02). Smoking status, alcohol intake, socioeconomic level, parity, age at first birth, and oral contraceptive use were not associated with the risk of glioma or meningioma tumours. In conclusion, for women in the United Kingdom, the incidence of glioma or meningioma tumours increases with increasing height and increasing BMI

Expression and functional activity of nucleoside transporters in human choroid plexus

Abstract Background Human equilibrative nucleoside transporters (hENTs) 1-3 and human concentrative nucleoside transporters (hCNTs) 1-3 in the human choroid plexus (hCP) play a role in the homeostasis of adenosine and other naturally occurring nucleosides in the brain; in addition, hENT1, hENT2 and hCNT3 mediate membrane transport of nucleoside reverse transcriptase inhibitors that could be used to treat HIV infection, 3'-azido-3'-deoxythymidine, 2'3'-dideoxycytidine and 2'3'-dideoxyinosine. This study aimed to explore the expression levels and functional activities of hENTs 1-3 and hCNTs 1-3 in human choroid plexus. Methods Freshly-isolated pieces of lateral ventricle hCP, removed for various clinical reasons during neurosurgery, were obtained under Local Ethics Committee approval. Quantification of mRNAs that encoded hENTs and hCNTs was performed by the hydrolysis probes-based reverse transcription real time-polymerase chain reaction (RT-qPCR); for each gene of interest and for 18 S ribosomal RNA, which was an endogenous control, the efficiency of PCR reaction (E) and the quantification cycle (Cq) were calculated. The uptake of [3H]inosine by the choroid plexus pieces was investigated to explore the functional activity of hENTs and hCNTs in the hCP. Results RT-qPCR revealed that the mRNA encoding the intracellularly located transporter hENT3 was the most abundant, with E-Cq value being only about 40 fold less that the E-Cq value for 18 S ribosomal RNA; mRNAs encoding hENT1, hENT2 and hCNT3 were much less abundant than mRNA for the hENT3, while mRNAs encoding hCNT1 and hCNT2 were of very low abundance and not detectable. Uptake of [3H]inosine by the CP samples was linear and consisted of an Na+-dependent component, which was probably mediated by hCNT3, and Na+-independent component, mediated by hENTs. The latter component was not sensitive to inhibition by S-(4-nitrobenzyl)-6-thioinosine (NBMPR), when used at a concentration of 0.5 μM, a finding that excluded the involvement of hENT1, but it was very substantially inhibited by 10 μM NBMPR, a finding that suggested the involvement of hENT2 in uptake. Conclusion Transcripts for hENT1-3 and hCNT3 were detected in human CP; mRNA for hENT3, an intracellularly located nucleoside transporter, was the most abundant. Human CP took up radiolabelled inosine by both concentrative and equilibrative processes. Concentrative uptake was probably mediated by hCNT3; the equilibrative uptake was mediated only by hENT2. The hENT1 transport activity was absent, which could suggest either that this protein was absent in the CP cells or that it was confined to the basolateral side of the CP epithelium.</p

A randomised controlled trial of Caphosol mouthwash in management of radiation-induced mucositis in head and neck cancer.

Purpose This phase III, non-blinded, parallel-group, randomised controlled study evaluated the efficacy of Caphosol mouthwash in the management of radiation-induced oral mucositis (OM) in patients with head and neck cancer (HNC) undergoing radical (chemo)radiotherapy.Patients and methods Eligible patients were randomised at 1:1 to Caphosol plus standard oral care (intervention) or standard oral care alone (control), stratified by radiotherapy technique and use of concomitant chemotherapy. Patients in the intervention arm used Caphosol for 7weeks: 6weeks during and 1-week post-radiotherapy. The primary endpoint was the incidence of severe OM (CTCAE ⩾grade 3) during and up to week 8 post-radiotherapy. Secondary endpoints include pharyngeal mucositis, dysphagia, pain and quality of life.Results The intervention (n=108) and control (n=107) arms were well balanced in terms of patient demographics and treatment characteristics. Following exclusion of patients with missing data, 210 patients were available for analysis. The incidence of severe OM did not differ between the intervention and control arms (64.1% versus 65.4%, p=0.839). Similarly, no significant benefit was observed for other secondary endpoints. Overall, compliance with the recommended frequency of Caphosol was low.Conclusion Caphosol did not reduce the incidence or duration of severe OM during and after radiotherapy in HNC