Ctr2 Links Copper Homeostasis to Polysaccharide Capsule Formation and Phagocytosis Inhibition in the Human Fungal Pathogen Cryptococcus neoformans

Cryptococcus neoformans is a human opportunistic fungal pathogen responsible for ∼1/3 of HIV/AIDS deaths worldwide. This budding yeast expresses a polysaccharide capsule necessary for virulence. Capsule production inhibits phagocytosis by macrophages. Here we describe results that link copper homeostasis to capsule production and the inhibition of phagocytosis. Specifically, using Agrobacterium-mediated insertional mutagenesis, we identified an insertion in the promoter region of the putative copper transporter-encoding gene CTR2 that results in reduced expression of CTR2 and increased phagocytosis by murine RAW264.7 macrophages. The mutant also displayed sensitivity to copper starvation and defects in polysaccharide capsule production and melanization. These defects were all reversed by genetic correction of the promoter insertion by homologous targeting. Several melanization-defective mutants identified previously, those in the RIM20, RIM101, and VPS25 genes, also display sensitivity to copper starvation, reduced capsule production and increased phagocytosis. Together these results indicate a previously undescribed link between copper homeostasis to polysaccharide capsule production and phagocytosis inhibition in Cryptococcus neoformans

Comparison of TCP and TCP/HA Hybrid Scaffolds for Osteoconductive Activity

Two types of porous ceramic scaffolds were prepared, consisting of β-tricalcium phosphate (TCP) or the mixed powder of TCP and hydroxyapatite (HA) at a 2:1 mass ratio. A variety of methods have been used to fabricate bone scaffolds, while the sintering approach was adopted in this work. An extremely high temperature was used on sintering that proposed to consolidate the ceramic particles. As revealed by SEM, a well opened pore structure was developed within the scaffolds. The θ-values were measured to be of 73.3° and 6.5° for the composite scaffold and TCP sample, respectively. According to XRD patterns, the existence of grains coalescence and partial bonding between HA and TCP powders was demonstrated. Scaffold mechanical property in the term of flexural strength was also determined. The result showed decreasing of the strength by HA supplement, suggesting the more brittle characteristic of HA in comparison with TCP. By soaking the composite scaffold in PBS for a period of 2 weeks, transformation from particles to flank-like crystalline was clearly observed. Such change was found to be favorable for cell attachment, migration, and growth. By implanting cell-seeded scaffolds into nude mice, an abundant osseous extracellular matrix was identified for the composite implants. In contrast, the matrix was minimally detected in TCP implanted samples. Thus, the composite scaffold was found superior for hard tissue regeneration

Urinary nitrate might be an early biomarker for pediatric acute kidney injury in the emergency department

NO is involved in normal kidney function and perturbed in acute kidney injury (AKI). We hypothesized that urinary concentration of NO metabolites, nitrite, and nitrate would be lower in children with early AKI presenting to the emergency department (ED), when serum creatinine (SCr) was uninformative. Patients up to 19 y were recruited if they had a urinalysis and SCr obtained for routine care. Primary outcome, AKI, was defined by pediatric Risk, Injury, Failure, Loss of function, End-stage renal disease (pRIFLE) criteria. Urinary nitrite and nitrate were determined by HPLC. A total of 252 patients were enrolled, the majority (93%) of whom were without AKI. Although 18 (7%) had AKI by pRIFLE, 50% may not have had it identified by the SCr value alone at the time of visit. Median urinary nitrate was lower for injury versus risk (p = 0.03); this difference remained significant when the injury group was compared against the combined risk and no AKI groups (p = 0.01). Urinary nitrite was not significantly different between groups. Thus, low urinary nitrate is associated with AKI in the pediatric ED even when SCr is normal. Predictive potential of this putative urinary biomarker for AKI needs further evaluation in sicker patients

Second law, entropy production, and reversibility in thermodynamics of information

We present a pedagogical review of the fundamental concepts in thermodynamics of information, by focusing on the second law of thermodynamics and the entropy production. Especially, we discuss the relationship among thermodynamic reversibility, logical reversibility, and heat emission in the context of the Landauer principle and clarify that these three concepts are fundamentally distinct to each other. We also discuss thermodynamics of measurement and feedback control by Maxwell's demon. We clarify that the demon and the second law are indeed consistent in the measurement and the feedback processes individually, by including the mutual information to the entropy production.Comment: 43 pages, 10 figures. As a chapter of: G. Snider et al. (eds.), "Energy Limits in Computation: A Review of Landauer's Principle, Theory and Experiments

Magnetism, FeS colloids, and Origins of Life

A number of features of living systems: reversible interactions and weak bonds underlying motor-dynamics; gel-sol transitions; cellular connected fractal organization; asymmetry in interactions and organization; quantum coherent phenomena; to name some, can have a natural accounting via $physical$ interactions, which we therefore seek to incorporate by expanding the horizons of `chemistry-only' approaches to the origins of life. It is suggested that the magnetic 'face' of the minerals from the inorganic world, recognized to have played a pivotal role in initiating Life, may throw light on some of these issues. A magnetic environment in the form of rocks in the Hadean Ocean could have enabled the accretion and therefore an ordered confinement of super-paramagnetic colloids within a structured phase. A moderate H-field can help magnetic nano-particles to not only overcome thermal fluctuations but also harness them. Such controlled dynamics brings in the possibility of accessing quantum effects, which together with frustrations in magnetic ordering and hysteresis (a natural mechanism for a primitive memory) could throw light on the birth of biological information which, as Abel argues, requires a combination of order and complexity. This scenario gains strength from observations of scale-free framboidal forms of the greigite mineral, with a magnetic basis of assembly. And greigite's metabolic potential plays a key role in the mound scenario of Russell and coworkers-an expansion of which is suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed Krishnaswami Alladi, Springer 201

Clinical significance of hypoalbuminemia in outcome of patients with scrub typhus

<p>Abstract</p> <p>Background</p> <p>This study was designed to investigate the clinical significance of hypoalbuminemia as a marker of severity and mortality in patients with Scrub typhus.</p> <p>Methods</p> <p>The patients with scrub typhus were divided into two groups based on the serum albumin levels; Group I (serum albumin <3.0 g/dL) and Group II (serum albumin ≥3.0 g/dL). The outcome of patients with hypoalbuminemia was compared with that of normoalbuminemia.</p> <p>Results</p> <p>Of the total 246 patients who underwent the study, 84 patients (34.1%) were categorized as Group I and 162 patients were (65.9%) as Group II. Group I showed significantly higher incidence of confusion (24.6% vs. 5.3%, <it>p </it>< 0.001), pulmonary edema (15.8% vs. 3.2%, <it>p </it>= 0.002), pleural effusion (22.8% vs. 11.1%, <it>p </it>= 0.03), arrhythmia (12.3% vs. 2.6%, <it>p </it>= 0.008) and non-oliguric acute renal failure (40.4% vs. 11.1%, <it>p </it>< 0.001) compared to group II. Hypoalbuminemic group had a higher APACHE II score (11.37 ± 5.0 vs. 6.94 ± 4.2, <it>p </it>< 0.001), longer hospital stay (19.9 ± 42.1 days vs 7.5 ± 13.8 days, <it>p </it>= 0.012), and higher hospital cost compared to Group II.</p> <p>Conclusions</p> <p>This study showed hypoalbuminemia in scrub typhus was closely related to the frequency of various complication, longer hospital stay, consequently the higher medical cost, necessitating more efficient management of patients, including medical resources.</p

Predictors of hospital mortality among septic ICU patients with Acinetobacter spp. bacteremia: A cohort study

BACKGROUND: We hypothesized that among septic ICU patients with Acinetobacter spp. bacteremia (Ac-BSI), carbapenem-resistant Acinetobacter spp. (CRAc) increase risk for inappropriate initial antibiotic therapy (non-IAAT), and non-IAAT is a predictor of hospital death. METHODS: We conducted a retrospective cohort study of adult septic ICU patients with Ac-BSI. Non-IAAT was defined as exposure to initially prescribed antibiotics not active against the pathogen based on in vitro susceptibility testing, and having no exposure to appropriate antimicrobial treatment within 24 hours of drawing positive culture. We compared patients who died to those who survived, and derived regression models to identify predictors of hospital mortality and of non-IAAT. RESULTS: Out of 131 patients with Ac-BSI, 65 (49.6%) died (non-survivors, NS). NS were older (63 [51, 76] vs. 56 [45, 66] years, p = 0.014), and sicker than survivors (S): APACHE II (24 [19, 31] vs. 18 [13, 22], p < 0.001) and Charlson (5 [2, 8] vs. 3 [1, 6], p = 0.009) scores. NS were also more likely than S to require pressors (75.4% vs. 42.4%, p < 0.001) and mechanical ventilation (75.4% vs. 53.0%, p = 0.008). Both CRAc (69.2% vs. 47.0%, p = 0.010) and non-IAAT (83.1% vs. 59.1%, p = 0.002) were more frequent among NS than S. In multivariate analyses, non-IAAT emerged as an independent predictor of hospital death (risk ratio [RR] 1.42, 95% confidence interval [CI] 1.10-1.58), while CRAc was the single strongest predictor of non-IAAT (RR 2.66, 95% CI 2.43-2.72). CONCLUSIONS: Among septic ICU patients with Ac-BSI, non-IAAT predicts mortality. Carbapenem resistance appears to mediate the relationship between non-IAAT and mortality

Hybrid SPECT/CT for the assessment of a painful hip after uncemented total hip arthroplasty

Background The diagnosis of hip pain after total hip replacement (THR) represents a highly challenging question that is of increasing concern to orthopedic surgeons. This retrospective study assesses bone scintigraphy with Hybrid SPECT/CT for the diagnosis of painful THR in a selected cohort of patients. Methods Bone SPECT/CT datasets of 23 patients (mean age 68.9 years) with a painful hip after THR were evaluated. Selection of the patients required an inconclusive radiograph, normal serum levels of inflammatory parameters (CRP and ESR) or a negative aspiration of the hip joint prior to the examination. The standard of reference was established by an interdisciplinary adjudication-panel using all imaging data and clinical follow-up data (>12 month). Pathological and physiological uptake patterns were defined and applied. Results The cause of pain in this study group could be determined in 18 out of 23 cases. Reasons were aseptic loosening (n = 5), spine-related (n = 5), heterotopic ossification (n = 5), neuronal (n = 1), septic loosening (n = 1) and periprosthetic stress fracture (n = 1). In (n = 5) cases the cause of hip pain could not be identified. SPECT/CT imaging correctly identified the cause of pain in (n = 13) cases, in which the integrated CT-information led to the correct diagnosis in (n = 4) cases, mainly through superior anatomic correlation. Loosening was correctly assessed in all cases with a definite diagnosis. Conclusions SPECT/CT of THA reliably detects or rules out loosening and provides valuable information about heterotopic ossifications. Furthermore differential diagnoses may be detected with a whole-body scan and mechanical or osseous failure is covered by CT- imaging. SPECT/CT holds great potential for imaging-based assessment of painful prostheses

Option selection in whole-body rotation movements in gymnastics

Abstract When a gymnast performs a somersault, the linear and angular momentum along with a particular control of inertia during the flight phase constrain the possibilities for action. Given the complexity and dynamic nature of the human moving system, one could argue that there exist a particular amount of stable coordination states when performing somersaults. The goal of this study was to explore the manifold of movement options and coordination states along with their differentiating parameters for a single somersault in gymnastics based on a simple mathematical model reflecting gymnast’s rotation behavior during the flight phase. Biomechanical parameters determining rotation behavior during a somersault were systematically varied with regard to a particular set of biomechanical constraints defining a successful somersault performance. Batch simulations revealed that from 10229760 simulation cycles only 655346 (approximately 6.41%) led to successful somersault performance. A subsequent analysis of the movement option landscape for the optimum angular momentum revealed ten coordination states for a single somersault that could be clearly distinguished based on the simulation parameters. Taken the results together, it becomes apparent that it may be most advisable to perform a single somersault with a larger moment of inertia when achieving the tucked position, a longer duration to achieve the tucked position, a longer duration of staying tucked, and an intermediate moment of inertia during landing. This strategy comprises the largest amount of movement options associated with an upright landing and thus the highest probability of success when performing a single somersault

Toxocariasis in children attending a Public Health Service Pneumology Unit in Paraná State, Brazil

The enzyme-linked immunosorbent assay (ELISA) is the most widely used tool to detect anti-Toxocara IgG antibodies for both serodiagnostic and seroepidemiological surveys on human toxocariasis. In the last eight years a high prevalence of toxocariasis (32.2-56.0%) has been reported in children attending public health units from municipalities in the state of Paraná, Brazil. Therefore, the aim of this work was to compare the frequency found among the general child population with that of children attending a public pneumology service in Maringá, Paraná, Brazil and describe the laboratorial, clinical and epidemiological findings. The research was conducted at the Consórcio Público Intermunicipal de Saúde do Setentrião Paranaense (CISAMUSEP) from July 2009 to July 2010 among children aged between one and 15 years. From a total of 167 children studied, only 4.2% (7/167) tested positive for anti-Toxocara spp. IgG antibodies and presented mild eosinophilia (2/7), increased serum IgE levels (6/7) and a positive allergy test for mites (5/7). The presence of pets (dogs or cats) at home did not correlate with the seroprevalence. In conclusion, cases of toxocariasis involving the respiratory tract are rare in children attending a public health pneumology unit in the northwestern region of Paraná State, despite the high prevalence of this type of toxocariasis among the infantile population attending Basic Health Units in the same geographical area