M-FISH analysis shows that complex chromosome aberrations induced by α-particle tracks are cumulative products of localised rearrangements

Complex chromosome aberrations are characteristically induced after exposure to low doses of densely ionising radiation, but little is understood about their formation. To address this, we irradiated human peripheral blood lymphocytes (PBL) in vitro with 0.5 Gy densely ionising α-particles (mean of 1 α-particle/cell) and analysed the chromosome aberrations produced using 24-colour M-FISH. Our data suggest that complex formation is a consequence of direct nuclear α-particle traversal and show that the likely product of illegitimate repair of damage from a single α-particle is a single complex exchange. From an assessment of the ‘cycle structure’ of each complex exchange we predict α-particle-induced damage to be repaired at specific localised sites, and complexes to be formed as cumulative products of this repair

Effect of linear energy transfer (LET) on complexity of alpha-particle-induced chromosome aberrations in human CD34+ cells.

The aim of this study was to assess the relative influence of linear energy transfer (LET) of α-particles on chromosome aberration complexity in the absence of significant other track structure differences. To do this we irradiated human haemopoietic stem cells (CD34+) with The aim of this study was to assess the relative influence of linear energy transfer (LET) of α-particles of various incident LET values (110 - 152 keV/µm, with mean LETs through the cell of 119 – 182 keV/µm) at an equi-fluence of approximately 1 α-particle/cell and assayed for chromosome aberrations by m-FISH. Based on a single harvest time to collect early division mitosis , complex aberrations were observed at comparable frequencies irrespective of incident LET, however when expressed as a proportion of the total exchanges detected, their occurrence was seen to increase with increasing LET. Cycle analysis to predict theoretical DNA double strand break rejoining cycles was also carried out on all complex chromosome aberrations detected. By doing this we found that the majority of complex aberrations are formed in single non-reducible cycles that involve just 2 or 3 different chromosomes and 3 or 4 different breaks. Each non-reducible cycle is suggested to represent ‘an area’ of finite size within the nucleus where double strand break repair occurs. We suggest that local density of damage induced and proximity of independent repair areas within the interphase nucleus determine the complexity of aberration resolved in metaphase. Overall, the most likely outcome of a single nuclear traversal of a single α-particle in CD34+ cells is a single chromosome aberration per damaged cell. As the incident LET of the α-particle increases, the likelihood of this aberration being classed as complex is greater

The hidden cost of a smartphone: The effects of smartphone notifications on cognitive control from a behavioral and electrophysiological perspective.

Since their release in 2007, smartphones and their use have seemingly become a fundamental aspect of life in western society. Prior literature has suggested a link between mobile technology use and lower levels of cognitive control when people engage in a cognitively demanding task. This effect is more evident for people who report higher levels of smartphone use. The current study examined the effects of smartphones notifications on cognitive control and attention. Participants completed the Navon Letter paradigm which paired visual (frequent and rare target letters) and auditory (smartphone and control sounds) stimuli. We found that overall, participants responded slower on trials paired with smartphone notification (vs. control) sounds. They also demonstrated larger overall N2 ERP and a larger N2 oddball effect on trials paired with smartphone (vs. control) sounds, suggesting that people generally exhibited greater levels of cognitive control on the smartphone trials. In addition, people with higher smartphone addiction proneness showed lower P2 ERP on trials with the smartphone (vs. control) sounds, suggesting lower attentional engagement. These results add to the debate on the effects of smartphones on cognition. Limitations and future directions are discussed

Surviving streptococcal toxic shock syndrome: a case report

Streptococcal toxic shock syndrome and associated myositis caused by group A beta-hemolytic streptococcus pyogenes generally have a poor outcome despite aggressive operative treatment. Frequently the diagnosis is missed initially as the clinical features are non-specific. The progression to a toxic state is rapid and unless definitive treatment measures are initiated early, the end result can be catastrophic. We report a previously healthy patient who had features of toxic shock syndrome due to alpha haemolytic (viridans) streptococcus mitis which was treated successfully with antibiotics, aggressive intensive care support including the use of a 'sepsis care bundle', monitoring and continuous multidisciplinary review. Life and limb threatening emergencies due to streptococcus mitis in an immune-competent person are rare and to our knowledge, have not previously been described in the English scientific literature. Successful outcome is possible provided a high degree of suspicion is maintained and the patient is intensively monitored

Single-Dose Oritavancin Treatment of Acute Bacterial Skin and Skin Structure Infections: SOLO Trial Efficacy by Eron Severity and Management Setting.

INTRODUCTION: Introduction of new antibiotics enabling single-dose administration, such as oritavancin may significantly impact site of care decisions for patients with acute bacterial skin and skin structure infections (ABSSSI). This analysis compared the efficacy of single-dose oritavancin with multiple-dose vancomycin in patients categorized according to disease severity via modified Eron classification and management setting. METHODS: SOLO I and II were phase 3 studies evaluating single-dose oritavancin versus 7-10 days of vancomycin for treatment of ABSSSI. Patient characteristics were collected at baseline and retrospectively analyzed. Study protocols were amended, allowing outpatient management at the discretion of investigators. In this post hoc analysis, patients were categorized according to a modified Eron severity classification and management setting (outpatient vs. inpatient) and the efficacy compared. RESULTS: Overall, 1910 patients in the SOLO trials were categorized into Class I (520, 26.5%), II (790, 40.3%), and III (600, 30.6%). Of the 767 patients (40%) in the SOLO trials who were managed entirely in the outpatient setting 40.3% were categorized as Class II and 30.6% were Class III. Clinical efficacy was similar between oritavancin and vancomycin treatment groups, regardless of severity classification and across inpatient and outpatient settings. Class III patients had lower response rates (oritavancin 73.3%, vancomycin 76.6%) at early clinical evaluation when compared to patients in Class I (82.6%) or II (86.1%); however, clinical cure rates at the post-therapy evaluation were similar for Class III patients (oritavancin 79.8%, vancomycin 79.9%) when compared to Class I and II patients (79.1-85.7%). CONCLUSION: Single-dose oritavancin therapy results in efficacy comparable to multiple-dose vancomycin in patients categorized according to modified Eron disease severity classification regardless of whether management occurred in the inpatient or outpatient setting. FUNDING: The Medicines Company, Parsippany, NJ, USA. TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT01252719 (SOLO I) and NCT01252732 (SOLO II)

Streptococcal necrotising fasciitis from diverse strains of Streptococcus pyogenes in tropical northern Australia: case series and comparison with the literature

BACKGROUND: Since the mid-1980's there has been a worldwide resurgence of severe disease from group A streptococcus (GAS), with clonal clusters implicated in Europe and the United States. However GAS associated sepsis and rheumatic fever have always remained at high levels in many less developed countries. In this context we aimed to study GAS necrotising fasciitis (NF) in a region where there are high background rates of GAS carriage and disease. METHODS: We describe the epidemiology, clinical and laboratory features of 14 consecutive cases of GAS NF treated over a seven year period from tropical northern Australia. RESULTS: Incidence rates of GAS NF in the Aboriginal population were up to five times those previously published from other countries. Clinical features were similar to those described elsewhere, with 7/14 (50%) bacteremic and 9/14 (64%) having associated streptococcal toxic shock syndrome. 11/14 (79%) had underlying chronic illnesses, including all four fatalities (29% mortality overall). Important laboratory differences from other series were that leukocytosis was absent in 9/14 (64%) but all had substantial lymphopenia. Sequence typing of the 14 NF-associated GAS isolates showed no clonality, with only one emm type 1 and two emm type 3 strains. CONCLUSIONS: While NF clusters can occur from a single emergent GAS clone, this was not evident in our tropical region, where high rates of NF parallel high overall rates of GAS infection from a wide diversity of strains. The specific virulence factors of GAS strains which do cause NF and the basis of the inadequate host response in those patients who develop NF on infection with these GAS require further elucidation

Fulminant Clostridium Septicum myonecrosis in well controlled diabetes: a case report

Diabetic myonecrosis with Clostridium Septicum is uncommon but carries a high mortality rate. This commensal organism is part of the gastrointestinal tract flora and can become extremely virulent, often in the setting of immuno-suppression such as neutropenia, occult malignancy (commonly caecal) and poorly controlled diabetes. The case report is unusual in that there are few risk factors other than very mild neutropenia. This highlights the opportunistic character of the organism and recommends that a high index of suspicion and vigilance be carried out in the presence of fevers and sepsis, even in the well-controlled diabetic population

Salmonella pyomyositis complicating sickle cell anemia: a case report

<p>Abstract</p> <p>Introduction</p> <p>Pyomyositis is a bacterial infection of skeletal muscle and a rare complication of sickle cell anemia. It may present a difficult problem in diagnosis, leading to delay in appropriate treatment and development of complications including abscess formation and osteomyelitis.</p> <p>Case presentation</p> <p>We report the case of a 44-year-old Afro-Caribbean woman with homozygous sickle cell disease who presented with chest crisis and later developed pyomyositis of her hip and pelvic muscles. <it>Salmonella agbeni </it>was isolated from blood cultures and magnetic resonance imaging confirmed the diagnosis in this case. It is noteworthy of this case that there were no antecedent signs of gastroenteritis. Drainage was not appropriate and she was treated with intravenous antibiotics for six weeks.</p> <p>Conclusions</p> <p>Focal Salmonella infections are uncommon in soft tissue. Pyomyositis should be considered in patients with sickle cell anemia that continue to have muscle pain and high fevers, despite initial management of their sickle cell crisis. Radiological imaging, particularly magnetic resonance imaging, is a crucial tool in establishing the diagnosis.</p

A model for selection of eyespots on butterfly wings

The development of eyespots on the wing surface of butterflies of the family Nympalidae is one of the most studied examples of biological pattern formation.However, little is known about the mechanism that determines the number and precise locations of eyespots on the wing. Eyespots develop around signaling centers, called foci, that are located equidistant from wing veins along the midline of a wing cell (an area bounded by veins). A fundamental question that remains unsolved is, why a certain wing cell develops an eyespot, while other wing cells do not. We illustrate that the key to understanding focus point selection may be in the venation system of the wing disc. Our main hypothesis is that changes in morphogen concentration along the proximal boundary veins of wing cells govern focus point selection. Based on previous studies, we focus on a spatially two-dimensional reaction-diffusion system model posed in the interior of each wing cell that describes the formation of focus points. Using finite element based numerical simulations, we demonstrate that variation in the proximal boundary condition is sufficient to robustly select whether an eyespot focus point forms in otherwise identical wing cells. We also illustrate that this behavior is robust to small perturbations in the parameters and geometry and moderate levels of noise. Hence, we suggest that an anterior-posterior pattern of morphogen concentration along the proximal vein may be the main determinant of the distribution of focus points on the wing surface. In order to complete our model, we propose a two stage reaction-diffusion system model, in which an one-dimensional surface reaction-diffusion system, posed on the proximal vein, generates the morphogen concentrations that act as non-homogeneous Dirichlet (i.e., fixed) boundary conditions for the two-dimensional reaction-diffusion model posed in the wing cells. The two-stage model appears capable of generating focus point distributions observed in nature. We therefore conclude that changes in the proximal boundary conditions are sufficient to explain the empirically observed distribution of eyespot focus points on the entire wing surface. The model predicts, subject to experimental verification, that the source strength of the activator at the proximal boundary should be lower in wing cells in which focus points form than in those that lack focus points. The model suggests that the number and locations of eyespot foci on the wing disc could be largely controlled by two kinds of gradients along two different directions, that is, the first one is the gradient in spatially varying parameters such as the reaction rate along the anterior-posterior direction on the proximal boundary of the wing cells, and the second one is the gradient in source values of the activator along the veins in the proximal-distal direction of the wing cell