Saturn Anomalous Myriametric Radiation, a New Type of Saturn Radio Emission Revealed by Cassini.

A new radio component namely Saturn Anomalous Myriametric Radiation (SAM) is reported. A total of 193 SAM events have been identified by using all the Cassini Saturn orbital data. SAM emissions are L-O mode radio emission and occasionally accompanied by a first harmonic in R-X mode. SAM's intensities decrease with increasing distance from Saturn, suggesting a source near Saturn. SAM has a typical central frequency near 13 kHz, a bandwidth greater than 8 kHz and usually drifts in frequency over time. SAM's duration can extend to near 11 hr and even longer. These features distinguish SAM from the regular narrowband emissions observed in the nearby frequency range, hence the name anomalous. The high occurrence rate of SAM after low frequency extensions of Saturn Kilometric Radiation and the SAM cases observed during compressions of Saturn's magnetosphere suggest a special connection to solar wind dynamics and magnetospheric conditions at Saturn.

Use of dabigatran with antiretrovirals.

OBJECTIVES: Theoretical and untested interactions between antiretrovirals and direct-acting oral anticoagulants have limited the use of this new class of anticoagulant in people with HIV infection. This case series, the first of its kind, reports on the successful concurrent use of the direct-acting oral anticoagulant dabigatran and antiretroviral therapy. METHODS: This series involved 14 patients requiring anticoagulation for management of atrial fibrillation, who were either unable or unwilling to take warfarin, and who were receiving concurrent treatment for HIV infection. Participants were treated with dabigatran with dose monitoring to establish the safety and efficacy of concurrent use with antiretrovirals. All were commenced on 110 mg twice daily, increased to 150 mg twice daily if the trough level was < 69.3 ng/mL. RESULTS: In the 14 patients treated with dabigatran and antiretrovirals, there were no thromboembolic or bleeding complications. Dabigatran treatment was discontinued in one patient because of undetectable dabigatran levels despite dose escalation. Dabigatran levels fell within the fivefold variance seen in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study at a dose of either 110 or 150 mg twice daily. CONCLUSIONS: This case series represents the largest published population to date successfully receiving antiretroviral and direct-acting oral anticoagulant therapy. Given the significant health care burden faced by people living with HIV, the availability of safe anticoagulant therapy without the requirement for monitoring is an important option in this patient population.

Peripherally Inserted Central Catheters (PICCs) and Potential Cost Savings and Shortened Bed Stays In an Acute Hospital Setting.

Peripheral inserted central catheters (PICCs) have increasingly become the mainstay of patients requiring prolonged treatment with antibiotics, transfusions, oncologic IV therapy and total parental nutrition. They may also be used in delivering a number of other medications to patients. In recent years, bed occupancy rates have become hugely pressurized in many hospitals and any potential solutions to free up beds is welcome. Recent introductions of doctor or nurse led intravenous (IV) outpatient based treatment teams has been having a direct effect on early discharge of patients and in some cases avoiding admission completely. The ability to deliver outpatient intravenous treatment is facilitated by the placement of PICCs allowing safe and targeted treatment of patients over a prolonged period of time. We carried out a retrospective study of 2,404 patients referred for PICCs from 2009 to 2015 in a university teaching hospital. There was an exponential increase in the number of PICCs requested from 2011 to 2015 with a 64% increase from 2012 to 2013. The clear increase in demand for PICCs in our institution is directly linked to the advent of outpatient intravenous antibiotic services. In this paper, we assess the impact that the use of PICCs combined with intravenous outpatient treatment may have on cost and hospital bed demand. We advocate that a more widespread implementation of this service throughout Ireland may result in significant cost savings as well as decreasing the number of patients on hospital trollies.

Lower coronary plaque burden in patients with HIV presenting with acute coronary syndrome.

OBJECTIVE: Treated HIV infection is associated with a higher incidence of coronary artery disease and myocardial infarction, although the mechanisms remain unclear. We sought to characterise the burden of coronary artery disease in men with HIV using retrospective data from invasive coronary angiograms in patients presenting with acute coronary syndrome (ACS). METHODS: Demographic and coronary angiographic data were obtained from 160 men with ST elevation myocardial infarction, non-STEMI or high-risk chest pain; 73 HIV-infected cases and 87 age-matched controls. The burden of coronary disease was calculated using the Gensini Angiographic Scoring System by 2 independent cardiologists blinded to HIV status. RESULTS: The 2 groups were matched for age, sex and cardiac event subtype and there was no difference in rates of smoking or cholesterol levels. Compared with control participants, patients with HIV had higher usage of antihypertensives (46 (63%) vs 30 (35%), p<0.001) and statins (47 (64%) vs 29 (33%), p<0.001). There was no difference in plaque distribution between both groups; however, the Gensini score was 42% lower in cases with HIV than in controls (p<0.03). C reactive protein was higher in cases with HIV (13.4±15.4 vs 3.7±3.6). CONCLUSIONS: Men with HIV presenting with ACS paradoxically had a lower burden of coronary plaque than matched controls, despite more aggressive risk factor management, suggesting that plaque vulnerability, rather than total burden of atherosclerosis, may be important in the pathophysiology of coronary artery disease in men with HIV.

Lopinavir and atazanavir in pregnancy: comparable infant outcomes, virological efficacies and preterm delivery rates.

OBJECTIVES: The aim of the study was to identify differences in infant outcomes, virological efficacy, and preterm delivery (PTD) outcome between women exposed to lopinavir/ritonavir (LPV/r) and those exposed to atazanavir/ritonavir (ATV/r). METHODS: A retrospective case note review was carried out. The case notes of 493 women who conceived while on LPV/r or ATV/r or initiated LPV/r or ATV/r during pregnancy and who delivered between 1 September 2007 and 30 August 2012 were reviewed. Data collected included demographics, antiretroviral use, HIV markers, and pregnancy and infant outcomes. Infant outcomes, virological efficacies and PTD rates for LPV/r and ATV/r were compared. RESULTS: A total of 306 women received LPV/r (82 conceiving while on the drug and 224 commencing it post-conception) and 187 received ATV/r (96 conceiving while on the drug and 91 commencing it post-conception). Comparing the two protease inhibitors (PIs), viral suppression rates were similar and, in women starting antiretroviral therapy (ART) post-conception, the median times to first undetectable HIV viral load were not significantly different (P = 0.64). PTD rates did not differ by therapy overall (ATV/r, 13%; LPV/r, 14%) or when considering the timing of first exposure (conceiving on ART, P = 0.81; commencing ART in pregnancy, P = 0.08). Poor fetal outcomes were very uncommon. There were two transmissions, giving a mother-to-child transmission (MTCT) rate of 0.4% (95% confidence interval 0.05-1.5%). CONCLUSIONS: Both ART regimens were well tolerated and successful in preventing MTCT. No significant differences in tolerability or in pregnancy or infant outcomes were observed, which supports the provision of a choice of PI in pregnancy.

Duplication 5q and deletion 9p due to a t(5;9)(q34;p23) in 2 cousins with features of Hunter-McAlpine syndrome and hypothyroidism.

We report on 2 similarly affected cousins with a compound imbalance resulting from a familial t(5;9)(q34;p23) and entailing both an ∼17-Mb 5q terminal duplication and an ∼12-Mb 9p terminal deletion as determined by G-banding, subtelomere FISH, and aCGH. The proband's karyotype was 46,XX,der(9)t(5;9)(q34;p23)mat.ish der(9)t(5;9)(q34;p23)(9pter-,5qter+).arr 5q34q35(163,328,000-180,629,000)×3, 9p24p23(194,000-12,664,000)×1. Her cousin had the same unbalanced karyotype inherited from his father. The clinical phenotype mainly consists of a distinct craniofacial dysmorphism featuring microcephaly, flat facies, down slanting palpebral fissures, small flat nose, long philtrum, and small mouth with thin upper lip. Additional remarkable findings were craniosynostosis of several sutures, craniolacunia and preaxial polydactyly in the proband and hypothyroidism in both subjects. The observed clinical constellation generally fits the phenotypic spectrum of the 5q distal duplication syndrome (known also as Hunter-McAlpine syndrome), except for the thyroid insufficiency which can likely be ascribed to the concurrent 9p deletion, as at least 4 other 9pter monosomic patients without chromosome 5 involvement had this hormonal disorder. The present observation further confirms the etiology of the HMS phenotype from gain of the 5q35→qter region, expands the clinical pictures of partial trisomy 5q and monosomy 9p, and provides a comprehensive list of 160 patients with 5q distal duplication.

A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy.

BACKGROUND: Optimal treatment remains uncertain for patients with cognitive impairment that persists or returns after standard IV antibiotic therapy for Lyme disease. METHODS: Patients had well-documented Lyme disease, with at least 3 weeks of prior IV antibiotics, current positive IgG Western blot, and objective memory impairment. Healthy individuals served as controls for practice effects. Patients were randomly assigned to 10 weeks of double-masked treatment with IV ceftriaxone or IV placebo and then no antibiotic therapy. The primary outcome was neurocognitive performance at week 12-specifically, memory. Durability of benefit was evaluated at week 24. Group differences were estimated according to longitudinal mixed-effects models. RESULTS: After screening 3368 patients and 305 volunteers, 37 patients and 20 healthy individuals enrolled. Enrolled patients had mild to moderate cognitive impairment and marked levels of fatigue, pain, and impaired physical functioning. Across six cognitive domains, a significant treatment-by-time interaction favored the antibiotic-treated group at week 12. The improvement was generalized (not specific to domain) and moderate in magnitude, but it was not sustained to week 24. On secondary outcome, patients with more severe fatigue, pain, and impaired physical functioning who received antibiotics were improved at week 12, and this was sustained to week 24 for pain and physical functioning. Adverse events from either the study medication or the PICC line were noted among 6 of 23 (26.1%) patients given IV ceftriaxone and among 1 of 14 (7.1%) patients given IV placebo; these resolved without permanent injury. CONCLUSION: IV ceftriaxone therapy results in short-term cognitive improvement for patients with posttreatment Lyme encephalopathy, but relapse in cognition occurs after the antibiotic is discontinued. Treatment strategies that result in sustained cognitive improvement are needed.

Estradiol and orexin-2 saporin actions on multiple forms of behavioral arousal in female mice.

Estrogens modulate almost all aspects of female behavioral arousal; however, apart from that of sexual behavior, the neurobiology of female arousal remains unclear. Because orexins-hypocretins are neurotransmitters known to be important for behavioral arousal, the authors hypothesized that orexins may be a target for estrogen. Gonadectomized female mice received an intracerebral injection of either phosphate-buffered saline, the neurotoxin saporin (SAP), or the orexin-2-saporin conjugate (OXSAP) in the lateral hypothalamus. SAP- and OXSAP-treated mice were also divided into groups receiving either estradiol capsules or oil capsules. Mice were tested in 3 behavioral tests measuring different modes of arousal: sensory responsiveness, running wheel activity, and fearfulness. OXSAP mice showed decreases in sensory responsiveness and fearfulness concomitant with a reduction in orexin cell number. Estradiol affected all behaviors tested but decreased fearfulness only when combined with OXSAP treatment. These data indicate that estrogens modulate orexins' effects on fearfulness.

Pyodermatitis-pyostomatitis vegetans complicated by methicillin-resistant Staphylococcus aureus infection.

Pyodermatitis-pyostomatitis vegetans (PPV), a rare disorder of the skin and oral mucosa, is considered a highly specific marker for inflammatory bowel disease, especially ulcerative colitis (UC). Oral lesions (pyostomatitis vegetans) are seen without skin involvement but rarely without gastrointestinal symptoms. Bowel symptoms may be minimal and precede the onset of other lesions by months or years. Dermatologically, PPV is characterized by annular, pustular lesions, which may precede or appear at the same time as the oral lesions. We report a case of PPV and UC in which presentation was confused by acneiform lesions and methicillin-resistant Staphylococcus aureus colonization. Management was complicated because of the patient's job commitments and need to travel, and the involvement of a number of different specialties at different locations.

Dental anomalies in Axenfeld-Rieger syndrome.

The authors describe the case of a 10-year-old girl presenting with Axenfeld-Rieger syndrome (ARS), a rare autosomal dominant condition. The patient showed severe hypodontia, microdontia and short roots. Early diagnosis of the syndrome from its dento-facial and systemic features is important so that subsequent ocular complications may be prevented.

Immediate exercise hyperemia in humans is contraction intensity dependent: evidence for rapid vasodilation.

We tested the hypothesis that rapid vasodilation proportional to contraction intensity contributes to the immediate (first cardiac cycle after initial contraction) exercise hyperemia. Ten healthy subjects performed single 1-s isometric forearm contractions at 5, 10, 15, 20, 30, 50, and 70% maximal voluntary contraction intensity (MVC) in arm above heart (AH) and below heart (BH) positions. Forearm blood flow (FBF; brachial artery mean blood velocity, Doppler ultrasound), mean arterial pressure (arterial tonometry), and heart rate (electrocardiogram) were measured beat by beat. Venous emptying (measured with a forearm strain gauge) was already maximized at 5% MVC, indicating that increases in contraction intensity did not further empty the forearm veins. Immediate increases in FBF were linearly proportional to contraction intensity from 5 to 70% MVC in AH (slope = 4.4 +/- 0.5%DeltaFBF/%MVC). In BH, the immediate increase in FBF demonstrated a curvilinear relationship with increasing contraction intensity and was greater than AH at 15, 20, 30, and 50% MVC (P < 0.05). Peak changes in FBF were greater in BH vs. AH from 10 to 50% MVC, even when venous refilling was complete (P < 0.05). These data support the existence of a rapid-acting vasodilatory mechanism(s) at the onset of human forearm exercise.

The RING domains of the promyelocytic leukemia protein PML and the arenaviral protein Z repress translation by directly inhibiting translation initiation factor eIF4E.

The promyelocytic leukemia protein (PML) is a mammalian regulator of cell growth which is characteristically disrupted in acute promyelocytic leukemia and by a variety of viruses. PML contains a RING domain which is required for its growth-suppressive and antiviral properties. Although normally nuclear, in certain pathogenic conditions, including arenaviral infection, PML is relocated to the cytoplasm, where its functions are poorly understood. Here, we observe that PML and arenavirus protein Z use regions around the first zinc-binding site of their respective RING domains to directly interact, with sub-micromolar affinity, with the dorsal surface of translation initiation factor eIF4E, representing a novel mode of eIF4E recognition. PML and Z profoundly reduce the affinity of eIF4E for its substrate, the 5' 7-methyl guanosine cap of mRNA, by over 100-fold. Association with the dorsal surface of eIF4E and direct antagonism of mRNA cap binding by PML and Z lead to direct inhibition of translation. These activities of the RING domains of PML and Z do not involve ubiquitin-mediated protein degradation, in contrast to many RINGs which have been observed to do so. Although PML and Z have well characterized physiological functions in regulation of growth and apoptosis, this work establishes the first discrete biochemical mechanism which underlies the biological activities of their RING domains. Thus, we establish PML and Z as translational repressors, with potential contributions to the pathogenesis of acute promyelocytic leukemia and variety of viral infections.

Gender-related differences in thrombogenic factors predicting recurrent cardiac events in patients after acute myocardial infarction. The THROMBO Investigators.

Thrombosis contributes to recurrent coronary events in patients after acute myocardial infarction (AMI), but prognostic significance of thrombogenic factors by gender is unknown. This study aimed to determine gender-related differences in the prognostic significance of thrombogenic factors for predicting cardiac events (nonfatal reinfarction or cardiac death) in postinfarction patients. Blood levels of the following factors were measured 2 months after AMI in 791 men and 254 women: fibrinogen, von Willebrand factor, factor VII and VIIa, plasminogen activator inhibitor, D-dimer, cholesterol, apolipoprotein A-1, apolipoprotein B, lipoprotein(a), triglycerides, and high-density lipoprotein cholesterol. After adjustment for clinical covariates, levels of apolipoprotein A, high-density lipoprotein cholesterol, fibrinogen, and factor VIIa were significantly higher in postinfarction women than men. During a mean 26-month follow-up, there were 67 cardiac events (8.5%) in men and 14 (5.5%) in women (p = 0.11). In the multivariate Cox model, elevated levels of factor VIIa were a significant predictor of cardiac events in women (p = 0.022) but not in men (p = 0.80), with significant gender-related effect (hazard ratio 2.80 vs 0.92, respectively; p <0.05). D-dimer had prognostic value in men (p = 0. 006) but not in women (p = 0.36), although the difference between hazard ratios for men and women was not significant (2.35 vs 1.58, respectively; p = 0.49). In conclusion, elevated levels of factor VIIa are associated with an increased risk of recurrent cardiac events in postinfarction women, but not in men. D-dimer is more predictive for cardiac events in postinfarction men than women. These observations indicate possible gender-related differences in the pathophysiologic mechanisms of recurrent cardiac events.

The lymphocytic choriomeningitis virus RING protein Z associates with eukaryotic initiation factor 4E and selectively represses translation in a RING-dependent manner.

Only a few host cell proteins that associate with arenaviruses have been identified. To date, the arenavirus Z protein associates with the promyelocytic leukemia protein PML and the ribosomal P proteins. The majority of PML is present in nuclear bodies which are translocated to the cytoplasm by infection with the arenavirus, lymphocytic choriomeningitis virus (LCMV). The Z protein is a small zinc-binding RING protein with an unknown function which is required for the viral life cycle. Here, we demonstrate an association between Z and the host cell translation factor, eukaryotic initiation factor 4E (eIF-4E) in infected and transfected cells. Z's association with both ribosomal proteins and this translation factor led us to investigate whether Z could modulate host cell translation. In cell culture, Z selectively represses protein production in an eIF-4E-dependent manner. Specifically, we see reduction in cyclin D1 protein production with no effect on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in cells transfected with Z. Previous reports indicate that cyclin D1 is sensitive to eIF-4E levels, whereas GAPDH is not. Consistent with this, we observe preferential downregulation of cyclin D1 during infection and no effect on GAPDH. Further, no changes in RNA levels were observed for cyclin D1 or GAPDH transcripts. The interaction between eIF-4E and Z may provide a mechanism for slower growth observed in infected cells and a viral strategy for establishing chronic infection.

Role of hypertension, diabetes, obesity, and race in the development of symptomatic myocardial dysfunction in a predominantly minority population with normal coronary arteries.

BACKGROUND: Hypertension, diabetes, and obesity have been reported as risk factors for both vascular and myocardial disease. Myocardial disease may be manifest as systolic or diastolic dysfunction. The development of coronary artery disease frequently obscures or confounds the myocardial disease. Our purpose was to study the effect of these risk factors and race on the frequency and severity of myocardial disease in the absence of coronary artery disease. METHODS AND RESULTS: We studied patients referred to the cardiac catheterization laboratory. We selected 233 patients with normal coronary arteries and excluded patients with other structural cardiac disorders and other causes of myocardial disease. Systolic function and diastolic function were determined. We gathered demographic, risk factor, clinical, and hemodynamic data on each patient. A multivariate analysis was performed to determine factors important to the development of myocardial disease in the absence of coronary artery disease. Diastolic dysfunction (44%) and systolic dysfunction (25%) were common findings. The 3 risk factors were found most often in black and Hispanic patients, but hypertension and obesity were most severe (P <.001) in black patients. Multivariate analysis indicated that a prior diagnosis of hypertension, level of systolic blood pressure, and severe obesity were the 3 factors independently associated with myocardial disease. CONCLUSIONS: Systolic dysfunction and diastolic dysfunction are common in patients with normal coronary arteries who have hypertension, diabetes, and/or obesity. Because these risk factors are so frequent and severe in the black population, myocardial disease is significantly more common in this segment of the population.