MRI confirms loss of blood–brain barrier integrity in a mouse model of disseminated candidiasis

Disseminated candidiasis primarily targets the kidneys and brain in mice and humans. Damage to these critical organs leads to the high mortality associated with such infections, and invasion across the blood–brain barrier can result in fungal meningoencephalitis. Candida albicans can penetrate a brain endothelial cell barrier in vitro through transcellular migration, but this mechanism has not been confirmed in vivo. MRI using the extracellular vascular contrast agent gadolinium diethylenetriaminepentaacetic acid demonstrated that integrity of the blood–brain barrier is lost during C. albicans invasion. Intravital two‐photon laser scanning microscopy was used to provide the first real‐time demonstration of C. albicans colonizing the living brain, where both yeast and filamentous forms of the pathogen were found. Furthermore, we adapted a previously described method utilizing MRI to monitor inflammatory cell recruitment into infected tissues in mice. Macrophages and other phagocytes were visualized in kidney and brain by the administration of ultrasmall iron oxide particles. In addition to obtaining new insights into the passage of C. albicans across the brain microvasculature, these imaging methods provide useful tools to study further the pathogenesis of C. albicans infections, to define the roles of Candida virulence genes in kidney versus brain infection and to assess new therapeutic measures for drug development. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.     

Iron Stores in Low and Normal Birth Weight Infants at Birth and in Early Infancy

Serum ferritin levels of low birth weight (LBW; BW?<?2,500 g) and normal birth weight (NBW; BW?≥?2,500 g) infants were evaluated at birth and at 3 mo using electrochemiluminescence immunoassay. At birth, levels were 318.6 (31.0–829.5) ng/mL in LBW (n?=?217) and 366.2 (122.4–858.5) ng/mL in NBW infants (n?=?116; p?<?0.01), with 1.4 % of LBW and none of the NBW infants having levels <12 ng/mL (p?=?0.20). At follow up, levels were 66.9 (4.5–567.7) ng/mL in LBW (n?=?126) and 126.2 (6.8–553.7) ng/mL in NBW infants (n?=?76; p?=?0.27), with 11.9 % of LBW and 11.8 % of NBW infants having levels <12 ng/mL (p?=?0.80).     

Phenothiazines and the electrocardiogram

Fifty-nine (42%) of 140 schizophrenic patients taking phenothiazines were found to have abnormal electrocardiograms. The abnormalities included T wave changes, S-T depression, P-R and Q-T prolongation, persistent sinus tachycardia (110 or more/min) and right bundle branch block.     

Chylothorax following innominate vein thrombosis--a rare complication of transvenous pacemaker implantation

A case of chylothorax following innominate vein thrombosis which developed as a late complication of transvenous pacemaker implantation is discussed. A 78-year-old man presented with a refractory left-sided pleural effusion, which turned out to be a chylothorax. He had undergone a transvenous pacemaker implantation 6 years earlier for sick sinus syndrome. Aetiological work-up showed occlusion of the innominate vein as the cause for the chylothorax. The chylothorax resolved following pleurodesis with talc slurry, and the innominate vein was recanalized by angioplasty. To our knowledge, this is the first report of a case of this nature.     

Epidermal growth factor receptor as a novel molecular target for aggressive papillary tumors in the middle ear and temporal bone

Adenomatous tumors in the middle ear and temporal bone are rare but highly morbid because they are difficult to detect prior to the development of audiovestibular dysfunction. Complete resection is often disfiguring and difficult because of location and the late stage at diagnosis, so identification of molecular targets and effective therapies is needed. Here, we describe a new mouse model of aggressive papillary ear tumor that was serendipitously discovered during the generation of a mouse model for mutant EGFR-driven lung cancer. Although these mice did not develop lung tumors, 43% developed head tilt and circling behavior. Magnetic resonance imaging (MRI) scans showed bilateral ear tumors located in the tympanic cavity. These tumors expressed mutant EGFR as well as active downstream targets such as Akt, mTOR and ERK1/2. EGFR-directed therapies were highly effective in eradicating the tumors and correcting the vestibular defects, suggesting these tumors are addicted to EGFR. EGFR activation was also observed in human ear neoplasms, which provides clinical relevance for this mouse model and rationale to test EGFR-targeted therapies in these rare neoplasms.     

Reduced global longitudinal and radial strain with normal left ventricular ejection fraction late after effective repair of aortic coarctation: a CMR feature tracking study

We sought to determine whether global and regional left ventricular (LV) strain parameters were altered in repaired coarctation of the aorta (COA) with normal LV ejection fraction (EF) when compared with healthy adult controls, and whether such alterations were related to LV hypertrophy (LVH). We identified 81 patients after COA repair (31 female, age 25 ± 8.5 years) with inclusion criteria at follow-up CMR of: age ≥13 years, time post-repair ≥10 years, no aortic valve disease, LV-EF >50 %). LV deformation indices derived using CMR-feature tracking and volumetric EF were compared between COA patients and normal controls (n = 20, 10 female, age 37 ± 7 years), and between COA with versus without LVH. In repaired COA versus controls, LV-EF (%) was 62 ± 7.2 versus 58 ± 3.0 (p = 0.01), and LV mass (g/m²) 66 ± 16.8 versus 57.7 ± 6.0 (p = 0.0001). LV global longitudinal strain (GLS) was decreased to ?17.0 ± 4.7 % in COA (?20 ± 5 % in controls, p = 0.02), and global radial strain (GRS) reduced to 40 ± 15 % (50 ± 12.4 % in controls, p = 0.003). The global circumferential strain (GCS) was preserved in COA at ?23 ± 4.7 % (?24.6 ± 2.4 % in controls, p = 0.14). Regionally, LS decrease was marked in the basal segments (septal, p = 0.005, lateral, p = 0.013). In COA with LVH (n = 45, mass 76.3 ± 12.8 g/m²) versus without LVH (n = 36, mass 52.2 ± 10 g/m²), GLS was more markedly decreased (?15.7 ± 4.8 vs. ?18.5 ± 4.2 %, p = 0.016, but GRS and GCS were similar (p = 0.49 and 0.27). In post-repair COA with normal LV-EF, GLS and GRS are reduced whilst GCS is preserved. GLS reduction is more pronounced in the presence of LVH. GLS may qualify as indicator of early LV dysfunction.     

Childhood adversity and traumatic exposures during deployment as predictors of mental health in Australian military veterans

Objective : To examine whether the relationship between traumatic exposure on deployment and poor mental health varies by the reported level of childhood adversity experienced in Australian military veterans deployed to the Bougainville or East Timor military operations. Methods : Cross‐sectional self‐reported survey data were collected in 2008 from 3,564 Australian military veterans who deployed to East Timor or Bougainville on their deployment experiences, health and recall of childhood events. Multivariable logistic regression was used to investigate the association between childhood adversity, deployment exposures and mental health. Results : The most common childhood adversity reported was ‘not having a special teacher, youth worker or family friend who looked out for them while growing up’. On average, responders reported experiencing 3.5 adverse childhood experiences (SD 2.7) and averaged 5.3 (SD 4.9) traumatic exposures on deployment. Both childhood adversity and traumatic exposures on deployment were associated with higher odds of poorer mental health. However, there was no evidence that level of childhood adversity modified the association between traumatic exposure and mental health. Conclusions/Implications : These findings suggest that military personnel who recalled a higher level of childhood adversity may need to be monitored for poor mental health and, if required, provided with appropriate support.     

Antibacterial activity of selected ethnomedicinal plants from South India

ObjectiveTo screen the antimicrobial potential of three ethnomedicinal plants Chassalia curviflora Thw. (C. curviflora), Cyclea peltata Hook. F. &; Thomson (C. peltata) and Euphorbia hirta L (E. hirta) used in folk medicines in Aarukani hills Kani tribe, Tamil Nadu, India against human bacterial pathogens.MethodsAntibacterial efficacy was performed by disc diffusion method against the pathogens viz., Escherichia coli (E. coli) (ATCC 35218), Staphylococcus aureus (S. aureus) (ATCC 6538), Salmonella typhi (S. typhi) (MTCC 733), Proteus vulgaris (P. vulgaris), Proteus mirabilis (P. mirabilis) and Streptococcus pyogenes (S. pyogenes) and incubated for 24 h at 37 °C.ResultsThe maximum degree of antibacterial activity was observed in C. peltata followed by C. curviflora. While E. hirta showed comparatively low degree of antibacterial activity. The methanolic extract of C. peltata showed the antibacterial activity against three pathogens viz., S. pyogenes, P. vulgaris and E. coli with the inhibition zones 12 mm, 10 mm and 9 mm, respectively. hexane extracts of C. peltata also showed the antibacterial activity against two selected pathogens viz., P. vulgaris and P. mirabilis with 15 mm and 12 mm of inhibition zones. All the three different concentrations (0.25, 0.50 &; 0.75 mg/mL) of methanolic extract of C. peltata show the inhibitory effect on the three susceptible bacteria S. pyogenes, P. vulgaris and E. coli with the maximum inhibition in the highest concentration (0.75 mg/mL). The methanolic and hexane extracts of C. curviflora exhibited the antibacterial activity against only one bacterium each i.e. P. vulgaris and S. typhi with the maximum zone of inhibition 13 and 11 mm respectively. The methanolic and hexane extracts of E. hirta exhibited the antibacterial activity against only one bacterium i.e. S. pyogenes with the maximum zone of inhibition 13 and 11 mm respectively.ConclusionsThe present investigation revealed that the C. curviflora, C. peltata and E. hirta are potentially good source of antibacterial agents and demonstrates the importance of such plants in traditional medicines.