Background. Zygomycosis is an increasingly emerging life-threatening infection. There is no single comprehensive literature review that describes the epidemiology and outcome of this disease. ...Methods. We reviewed reports of zygomycosis in the English-language literature since 1885 and analyzed 929 eligible cases. We included in the database only those cases for which the underlying condition, the pattern of infection, the surgical and antifungal treatments, and survival were described. Results. The mean age of patients was 38.8 years; 65% were male. The prevalence and overall mortality were 36% and 44%, respectively, for diabetes; 19% and 35%, respectively, for no underlying condition; and 17% and 66%, respectively, for malignancy. The most common types of infection were sinus (39%), pulmonary (24%), and cutaneous (19%). Dissemination developed in 23% of cases. Mortality varied with the site of infection: 96% of patients with disseminated disease died, 85% with gastrointestinal infection died, and 76% with pulmonary infection died. The majority of patients with malignancy (92 60% of 154) had pulmonary disease, whereas the majority of patients with diabetes (222 66% of 337) had sinus disease. Rhinocerebral disease was seen more frequently in patients with diabetes (145 33% of 337), compared with patients with malignancy (6 4% of 154). Hematogenous dissemination to skin was rare; however, 78 (44%) of 176 cutaneous infections were complicated by deep extension or dissemination. Survival was 3% (8 of 241 patients) for cases that were not treated, 61% (324 of 532) for cases treated with amphotericin B deoxycholate, 57% (51 of 90) for cases treated with surgery alone, and 70% (328 of 470) for cases treated with antifungal therapy and surgery. By multivariate analysis, infection due to Cunninghamella species and disseminated disease were independently associated with increased rates of death (odds ratios, 2.78 and 11.2, respectively). Conclusions. Outcome from zygomycosis varies as a function of the underlying condition, site of infection, and use of antifungal therapy.
A statistical downscaling method (SDSM) was evaluated by simultaneously downscaling air temperature, evaporation, and precipitation in Haihe River basin, China. The data used for evaluation were ...large-scale atmospheric data encompassing daily NCEP/NCAR reanalysis data and the daily mean climate model results for scenarios A2 and B2 of the HadCM3 model. Selected as climate variables for downscaling were measured daily mean air temperature, pan evaporation, and precipitation data (1961–2000) from 11 weather stations in the Haihe River basin. The results obtained from SDSM showed that: (1) the pattern of change in and numerical values of the climate variables can be reasonably simulated, with the coefficients of determination between observed and downscaled mean temperature, pan evaporation, and precipitation being 99%, 93%, and 73%, respectively; (2) systematic errors existed in simulating extreme events, but the results were acceptable for practical applications; and (3) the mean air temperature would increase by about 0.7°C during 2011~2040; the total annual precipitation would decrease by about 7% in A2 scenario but increase by about 4% in B2 scenario; and there were no apparent changes in pan evaporation. It was concluded that in the next 30 years, climate would be warmer and drier, extreme events could be more intense, and autumn might be the most distinct season among all the changes.
A reversal of magnetization requiring only the application of an electric field can lead to low-power spintronic devices by eliminating conventional magnetic switching methods. Here we show a ...nonvolatile, room temperature magnetization reversal determined by an electric field in a ferromagnet-multiferroic system. The effect is reversible and mediated by an interfacial magnetic coupling dictated by the multiferroic. Such electric-field control of a magnetoelectric device demonstrates an avenue for next-generation, low-energy consumption spintronics.
Background. Candida species are the fourth most common cause of bloodstream infection and are the leading cause of invasive fungal infection among hospitalized patients in the United States. However, ...the frequency and outcomes attributable to the infection are uncertain. This retrospective study set out to estimate the incidence of candidemia in hospitalized adults and children in the United States and to determine attributable mortality, length of hospital stay, and hospital charges related to candidemia. Methods. We used the Nationwide Inpatient Sample 2000 for adult patients and the Kids' Inpatient Database 2000 for pediatric patients. We matched candidemia-exposed and candidemia-unexposed patients by the propensity scores for the probability of candidemia exposure, which were derived from patient characteristics. Attributable outcomes were calculated as the differences in estimates of outcomes between propensity score–matched patients with and without candidemia. Results. In the United States in 2000, candidemia was diagnosed in an estimated 1118 hospital admissions of pediatric patients and 8949 hospital admissions of adult patients, yielding a frequency of 43 cases per 100,000 pediatric admissions (95% confidence interval CI, 35–52 cases per 100,000 pediatric admissions) and 30 cases per 100,000 adult admissions (95% CI, 26–34 cases per 100,000 adult admissions). In pediatric patients, candidemia was associated with a 10.0% increase in mortality (95% CI, 6.2%–13.8%), a mean 21.1-day increase in length of stay (95% CI, 14.4–27.8 days), and a mean increase in total per-patient hospital charges of $92,266 (95% CI, $65,058–$119,474). In adult patients, candidemia was associated with a 14.5% increase in mortality (95% CI, 12.1%–16.9%), a mean 10.1-day increase in length of stay (95% CI, 8.9–11.3 days), and a mean increase in hospital charges of $39,331 (95% CI, $33,604–$45,602). Conclusion. The impact of candidemia on excess mortality, increased length of stay, and the burden of cost of hospitalization underscores the need for improved means of prevention and treatment of candidemia in adults and children.
Summary
Background Previous studies have demonstrated that the lack of lumican delayed corneal wound healing in lumican‐null (Lum−/−) mice. This defect is rescued by the addition of glycosylated ...lumican core protein to the injured corneas.
Objectives We examined the hypothesis that lumican is also required for the healing of cutaneous wounds using Lum−/− mice.
Methods We demonstrated the basic thinner skin phenotypes in Lum−/− mice at different time points and the changes in arrangement of collagen fibres by transmission electron microscopy (TEM). A full skin thickness wound was generated by punch biopsy (6 mm diameter) in experimental Lum−/− and wild‐type mice. The closure of injured skin was measured after various periods of time (3, 6, 12, 18 days). Specimens of injured and uninjured skin (serving as control) were then subjected to morphological examination with haematoxylin and eosin and Masson trichrome stains, and by TEM. Immunohistochemical staining with anti‐CD68 antibody was used to assess the presence of macrophages in injured skin healing for various periods of time. Semiquantitative reverse transcription–polymerase chain reaction (RT‐PCR) was used to elucidate the transforming growth factor (TGF)‐β1‐induced myofibroblast phenotypic genes.
Results Skin of adult Lum−/− mice (3 months and older) was much thinner (40% less) than that of age‐matched wild‐type mice. This phenomenon was aggravated in older mice. TEM revealed disoriented and irregular collagen fibrils in the dermis of Lum−/− mice. Delayed wound healing with an increase in inflammatory macrophages was compatible with the delayed response of the expression of TGF‐β1, type I collagen α1 and fibronectin at the mRNA level by semiquantitative RT‐PCR in the Lum−/− mice.
Conclusions Our data demonstrate that lumican plays pivotal roles in skin collagen fibrillogenesis and wound healing.
We have previously demonstrated that peroxisome proliferator-activated receptor (PPARγ) activation inhibits hepatocarcinogenesis. We aim to investigate the effect of PPARγ on hepatocellular carcinoma ...(HCC) metastatic potential and explore its underlying mechanisms.
Human HCC cells (MHCC97L, BEL-7404) were infected with adenovirus-expressing PPARγ (Ad-PPARγ) or Ad-lacZ and treated with or without PPARγ agonist (rosiglitazone). The effects of PPARγ on cell migration and invasive activity were determined by wound healing assay and Matrigel invasive model in vitro, and in an orthotopic liver tumour metastatic model in mice.
Pronounced expression of PPARγ was demonstrated in HCC cells (MHCC97L, BEL-7404) treated with Ad-PPARγ, rosiglitazone or Ad-PPARγ plus rosiglitazone, compared with control (Ad-LacZ). Such induction markedly suppressed HCC cell migration. Moreover, the invasiveness of MHCC97L and BEL-7404 cells infected with Ad-PPARγ, or treated with rosiglitazone was significantly diminished up to 60%. Combination of Ad-PPARγ and rosiglitazone showed an additive effect. Activation of PPARγ by rosiglitazone significantly reduced the incidence and severity of lung metastasis in an orthotopic HCC mouse model. Key mechanisms underlying the effect of PPARγ in HCC include upregulation of cell adhesion genes, E-cadherin and SYK (spleen tyrosine kinase), extracellular matrix regulator tissue inhibitors of metalloproteinase (TIMP) 3, tumour suppressor gene retinoblastoma 1, and downregulation of pro-metastatic genes MMP9 (matrix metallopeptidase 9), MMP13, HPSE (heparanase), and Hepatocyte growth factor (HGF). Direct transcriptional regulation of TIMP3, MMP9, MMP13, and HPSE by PPARγ was shown by ChIP-PCR.
Peroxisome proliferator-activated receptor-gamma exerts an inhibitory effect on the invasive and metastatic potential of HCC in vitro and in vivo, and is thus, a target for the prevention and treatment of HCC metastases.
The aortic valve exhibits complex three-dimensional (3D) anatomy and heterogeneity essential for the long-term efficient biomechanical function. These are, however, challenging to mimic in de novo ...engineered living tissue valve strategies. We present a novel simultaneous 3D printing photocrosslinking technique for rapidly engineering complex, heterogeneous aortic valve scaffolds. Native anatomic and axisymmetric aortic valve geometries (root wall and tri-leaflets) with 12-22 mm inner diameters (ID) were 3D printed with poly-ethylene glycol-diacrylate (PEG-DA) hydrogels (700 or 8000 MW) supplemented with alginate. 3D printing geometric accuracy was quantified and compared using Micro-CT. Porcine aortic valve interstitial cells (PAVIC) seeded scaffolds were cultured for up to 21 days. Results showed that blended PEG-DA scaffolds could achieve over tenfold range in elastic modulus (5.3±0.9 to 74.6±1.5 kPa). 3D printing times for valve conduits with mechanically contrasting hydrogels were optimized to 14 to 45 min, increasing linearly with conduit diameter. Larger printed valves had greater shape fidelity (93.3±2.6, 85.1±2.0 and 73.3±5.2% for 22, 17 and 12 mm ID porcine valves; 89.1±4.0, 84.1±5.6 and 66.6±5.2% for simplified valves). PAVIC seeded scaffolds maintained near 100% viability over 21 days. These results demonstrate that 3D hydrogel printing with controlled photocrosslinking can rapidly fabricate anatomical heterogeneous valve conduits that support cell engraftment.
NRLMSIS® 2.0 is an empirical atmospheric model that extends from the ground to the exobase and describes the average observed behavior of temperature, eight species densities, and mass density via a ...parametric analytic formulation. The model inputs are location, day of year, time of day, solar activity, and geomagnetic activity. NRLMSIS 2.0 is a major, reformulated upgrade of the previous version, NRLMSISE‐00. The model now couples thermospheric species densities to the entire column, via an effective mass profile that transitions each species from the fully mixed region below ~70 km altitude to the diffusively separated region above ~200 km. Other changes include the extension of atomic oxygen down to 50 km and the use of geopotential height as the internal vertical coordinate. We assimilated extensive new lower and middle atmosphere temperature, O, and H data, along with global average thermospheric mass density derived from satellite orbits, and we validated the model against independent samples of these data. In the mesosphere and below, residual biases and standard deviations are considerably lower than NRLMSISE‐00. The new model is warmer in the upper troposphere and cooler in the stratosphere and mesosphere. In the thermosphere, N2 and O densities are lower in NRLMSIS 2.0; otherwise, the NRLMSISE‐00 thermosphere is largely retained. Future advances in thermospheric specification will likely require new in situ mass spectrometer measurements, new techniques for species density measurement between 100 and 200 km, and the reconciliation of systematic biases among thermospheric temperature and composition data sets, including biases attributable to long‐term changes.
Key Points
A major, reformulated upgrade to NRLMSISE‐00 is presented using extensive new data sets from the ground to ~100 km altitude
Vertical structure of the atmosphere is now self‐consistently coupled; O density now extends down to 50 km
New model is warmer in upper troposphere, cooler in stratosphere and mesosphere; thermospheric N2 and O densities are lower
Summary
Background Alopecia areata (AA) may be related to stress and has been reported to be associated with psychiatric disorders. Nevertheless, a nationwide study of the relationship between AA ...and comorbid psychiatric diseases has not been conducted, and the effect of onset age has rarely been reported.
Objectives To analyse the associations between AA and various psychiatric disorders using a nationwide database in Taiwan.
Methods Data were obtained from the National Health Insurance Research Database of Taiwan from 2000 to 2009. In total, 5117 patients with AA and 20 468 age‐ and gender‐matched controls were enrolled.
Results Patients with AA tended to have more coexisting anxiety and less comorbid schizophrenia. Differences in ages of onset revealed differences in comorbidities. An increased risk of depression odds ratio (OR) 2·23; 95% confidence interval (CI) 1·09–4·54 was found in patients with AA aged < 20 years. An increased rate of anxiety (OR 1·43; CI 1·15–1·77) was observed with AA onset between the ages of 20 and 39 years. The highest odds of obsessive–compulsive disorder (OR 3·00; CI 1·11–8·12) and anxiety (OR 2·05; CI 1·56–2·68) were observed in patients with AA aged 40–59 years. Moreover, about 50% of psychiatric disorders occurred earlier than AA.
Conclusions AA is related to various psychiatric disorders. Onset age of AA is an important factor in the association with different comorbid psychiatric diseases. In addition to cosmetic impact, which may bring about anxiety or depression, stress neuroendocrine immunology may play an important role in the pathogenesis of both AA and psychiatric disorders.
Magnetoelectrics and multiferroics present exciting opportunities for electric-field control of magnetism. However, there are few room-temperature ferromagnetic-ferroelectrics. Among the various ...types of multiferroics the bismuth ferrite system has received much attention primarily because both the ferroelectric and the antiferromagnetic orders are quite robust at room temperature. Here we demonstrate the emergence of an enhanced spontaneous magnetization in a strain-driven rhombohedral and super-tetragonal mixed phase of BiFeO₃. Using X-ray magnetic circular dichroism-based photoemission electron microscopy coupled with macroscopic magnetic measurements, we find that the spontaneous magnetization of the rhombohedral phase is significantly enhanced above the canted antiferromagnetic moment in the bulk phase, as a consequence of a piezomagnetic coupling to the adjacent tetragonal-like phase and the epitaxial constraint. Reversible electric-field control and manipulation of this magnetic moment at room temperature is also shown.
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