Recognition and Clinical Presentation of Invasive Fungal Disease in Neonates and Children

AW and JK are supported by the Wellcome Trust Strategic Award (grant 097377) and the MRC Centre for Medical Mycology (grant MR/N006364/1) at the University of AberdeenPeer reviewedPublisher PD

Potential Microbiological Effects of Higher Dosing of Echinocandins

The antifungal "paradoxical effect” has been described as the reversal of growth inhibition at high doses of echinocandins, most usually caspofungin. This microbiological effect appears to be a cellular compensatory response to cell wall damage, resulting in alteration of cell wall content and structure as well as fungal morphology and growth. In vitro studies demonstrate this reproducible effect in a certain percentage of fungal isolates, but animal model and clinical studies are less consistent. The calcineurin and Hsp90 cell signaling pathways appear to play a major role in regulating these cellular and structural changes. Regardless of the clinical relevance of this paradoxical growth effect, understanding the specific actions of echinocandins is paramount to optimizing their use at either standard or higher dosing schemes, as well as developing future improvements in our antifungal arsena

Antifungal activity of compounds targeting the Hsp90-calcineurin pathway against various mould species

Objectives Invasive mould infections are associated with a high mortality rate and the emergence of MDR moulds is of particular concern. Calcineurin and its chaperone, the heat shock protein 90 (Hsp90), represent an important pathway for fungal virulence that can be targeted at different levels. We investigated the antifungal activity of compounds directly or indirectly targeting the Hsp90-calcineurin axis against different mould species. Methods The in vitro antifungal activity of the anticalcineurin drug FK506 (tacrolimus), the Hsp90 inhibitor geldanamycin, the lysine deacetylase inhibitor trichostatin A and the Hsp70 inhibitor pifithrin-μ was assessed by the standard broth dilution method against 62 clinical isolates of Aspergillus spp. and non-Aspergillus moulds (Mucoromycotina, Fusarium spp., Scedosporium spp., Purpureocillium/Paecilomyces spp. and Scopulariopsis spp.) Results FK506 had variable antifungal activity against different Aspergillus spp. and was particularly active against Mucor spp. Geldanamycin had moderate antifungal activity against Fusarium spp. and Paecilomyces variotii. Importantly, trichostatin A had good activity against the triazole-resistant Aspergillus ustus and the amphotericin B-resistant Aspergillus terreus as well as the MDR Scedosporium prolificans. Moreover, trichostatin A exhibited synergistic interactions with caspofungin against A. ustus and with geldanamycin against Rhizopus spp. for which none of the other agents showed activity. Pifithrin-μ exhibited little antifungal activity. Conclusions Targeting the Hsp90-calcineurin axis at different levels resulted in distinct patterns of susceptibility among different fungal species. Lysine deacetylase inhibition may represent a promising novel antifungal strategy against emerging resistant mould

Frecuencia de factores asociados a ideación suicida en pacientes con fibromialgia en dos hospitales de Lambayeque 2015

Objetivo: determinar la frecuencia de los factores asociados a ideación suicida en pacientes con fibromialgia en dos hospitales de Lambayeque, 2015. Material y Métodos: estudio descriptivo transversal con análisis exploratorio. Se entrevistó a pacientes con fibromialgia de consultorios externos de los hospitales Regional Lambayeque (Hospital 1) y Almanzor Aguinaga Asenjo de Chiclayo (Hospital 2). Se aplicaron 5 cuestionarios: la escala del centro de estudios epidemiológicos para depresión, escala de Zung para ansiedad, índice de calidad de sueño de Pittsburgh, escala de valoración análoga del dolor y la escala de ideación suicida de Beck, adaptada a población Lambayecana. Se realizó análisis univariado y bivariado exploratorio. Resultados: Se entrevistaron 125 pacientes, 61 del hospital 1 y 64 del Hospital 2; 87%, fueron mujeres. Hubieron 73,6% malos dormidores, 68% tuvieron depresión, 22,4% ansiedad, 24,8% dolor corporal difuso moderado-severo y 30,4% ideación suicida, 27,9% y 32,8% en el primer y segundo hospital, respectivamente. En los pacientes con Ideación suicida la frecuencia fue: mala calidad del sueño 81,6% (p=0,1), depresión 71%(p=0,5), ansiedad 42% (0,001) y dolor corporal difuso (DCD) de moderado a severo 26,3% (p=0,005). En el multivariado, ansiedad, rp= 1,4 IC95%= 1,14-1,7, p= 0,006 y ser mal dormidor, rp= 1,2, IC95%= 1,0-1,4, p=0,01 se asociaron a Ideación suicida. Conclusiones: la frecuencia de ideación suicida es elevada en estos pacientes. El factor más frecuente fue mala calidad de sueño. Ansiedad y ser mal dormidor se asociaron a ideación suicida.Tesi

Tumoral calcinosis: radiologic-pathologic correlation

Tumoral calcinosis is a frequently misdiagnosed disorder. This study details the radiologic and pathologic characteristics of tumoral calcinosis that distinguish it from most other entities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46807/1/256_2004_Article_BF00204854.pd

Epidemiology and outcomes of candidemia in 2019 patients: data from the prospective antifungal therapy alliance registry.

BACKGROUND: Candidemia remains a major cause of morbidity and mortality in the health care setting, and the epidemiology of Candida infection is changing. METHODS: Clinical data from patients with candidemia were extracted from the Prospective Antifungal Therapy (PATH) Alliance database, a comprehensive registry that collects information regarding invasive fungal infections. A total of 2019 patients, enrolled from 1 July 2004 through 5 March 2008, were identified. Data regarding the candidemia episode were analyzed, including the specific fungal species and patient survival at 12 weeks after diagnosis. RESULTS: The incidence of candidemia caused by non-Candida albicans Candida species (54.4%) was higher than the incidence of candidemia caused by C. albicans (45.6%). The overall, crude 12-week mortality rate was 35.2%. Patients with Candida parapsilosis candidemia had the lowest mortality rate (23.7%; P CONCLUSIONS: The epidemiology and choice of therapy for candidemia are rapidly changing. Additional study is warranted to differentiate host factors and differences in virulence among Candida species and to determine the best therapeutic regimen

Design and Performance of 30/40 GHz Diplexed Focal Plane for BICEP Array

We demonstrate a wide-band diplexed focal plane suitable for observing low-frequency foregrounds that are important for cosmic microwave background polarimetry. The antenna elements are composed of slotted bowtie antennas with 60% bandwidth that can be partitioned into two bands. Each pixel is composed of two interleaved 12$\times$12 pairs of linearly polarized antenna elements forming a phased array, designed to synthesize a symmetric beam with no need for focusing optics. The signal from each antenna element is captured in-phase and uniformly weighted by a microstrip summing tree. The antenna signal is diplexed into two bands through the use of two complementary, six-pole Butterworth filters. This filter architecture ensures a contiguous impedance match at all frequencies, and thereby achieves minimal reflection loss between both bands. Subsequently, out-of-band rejection is increased with a bandpass filter and the signal is then deposited on a transition-edge sensor bolometer island. We demonstrate the performance of this focal plane with two distinct bands, 30 and 40 GHz, each with a bandwidth of $\sim$20 and 15 GHz, respectively. The unequal bandwidths between the two bands are caused by an unintentional shift in diplexer frequency from its design values. The end-to-end optical efficiency of these detectors are relatively modest, at 20-30%, with an efficiency loss due to an unknown impedance mismatch in the summing tree. Far-field beam maps show good optical characteristics with edge pixels having no more than $\sim$ 5% ellipticity and $\sim$10-15% peak-to-peak differences for A-B polarization pairs.Comment: 17 pages, 13 figures. Accepted for publication in ApJ