Hepatitis E virus (HEV) genotype 4 (HEV-4) is an emerging cause of acute hepatitis in China. Less is known about the clinical characteristics and natural history of HEV-4 than HEV genotype 3 ...infections in immunocompromised patients. We report transmission of HEV-4 from a deceased organ donor to 5 transplant recipients. The donor had been viremic but HEV IgM and IgG seronegative, and liver function test results were within reference ranges. After a mean of 52 days after transplantation, hepatitis developed in all 5 recipients; in the liver graft recipient, disease was severe and with progressive portal hypertension. Despite reduced immunosuppression, all HEV-4 infections progressed to persistent hepatitis. Four patients received ribavirin and showed evidence of response after 2 months. This study highlights the role of organ donation in HEV transmission, provides additional data on the natural history of HEV-4 infection, and points out differences between genotype 3 and 4 infections in immunocompromised patients.
Diverse Applications of Nanomedicine Pelaz, Beatriz; Alexiou, Christoph; Alvarez-Puebla, Ramon A ...
ACS nano,
03/2017, Letnik:
11, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of ...areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic.
Idiopathic granulomatous mastitis (IGM) is an uncommon, chronic inflammatory breast disease with elusive aetiology, simulating malignancy clinically and radiologically. Here we present our 10-year ...review on a region-wide multicentre IGM database. A retrospective study was performed on a prospectively maintained database from three University affiliated hospitals in Hong Kong and Shenzhen, China. All patients with biopsy proven IGM were included while patients with positive culture of Mycobacterium tuberculosis were excluded. Disease recurrence rate and its prognosticators were evaluated. A total of 102 patients were included between January 2007 and December 2017. Median age was 33 years (range 20–54). Most patients presented with painful inflammatory mass (n = 57); median size at presentation was 37 mm (6–92 mm). Sixty-three patients had bacterial culture performed on the pus sample: eight patients had Corynebacterium kroppenstedtii while four had Corynebacterium species not otherwise specified. Seventy-seven (75.5%) patients received conservative treatment with oral corticosteroid (±antibiotics) and drainage only, while 25 (24.5%) patients received breast lump excision after initial medical treatment. Twelve (11.8%) patients developed recurrence after a median follow-up interval of 14 months (4–51 months). Univariate analysis revealed that abscess on presentation, history of smoking, and presence of C. kroppenstedtii were significant prognosticators for recurrence. Subsequent multivariate analysis with logistic regression revealed cigarette smoking and isolation of C. kroppenstedtii as independent risk factors for disease recurrence (p < 0.05). In conclusion, IGM is uncommon with a recurrence rate of 12%, especially in patients with history of smoking and isolation of C. kroppenstedtii.
To compare the image quality and dosimetry on the Varian cone beam computed tomography (CBCT) system between software Version 1.4.13 and Version 1.4.11 (referred to as "new" and "old" protocols, ...respectively, in the following text). This study investigated organ absorbed dose, total effective dose, and image quality of the CBCT system for the head-and-neck and pelvic regions.
A calibrated Farmer chamber and two standard cylindrical Perspex CT dosimetry phantoms with diameter of 16 cm (head phantom) and 32 cm (body phantom) were used to measure the weighted cone-beam computed tomography dose index (CBCTDIw) of the Varian CBCT system. The absorbed dose of different organs was measured in a female anthropomorphic phantom with thermoluminescent dosimeters (TLD) and the total effective dose was estimated according to International Commission on Radiological Protection (ICRP) Publication 103. The dose measurement and image quality were studied for head-and-neck and pelvic regions, and comparison was made between the new and old protocols.
The values of the new CBCTDIw head-and-neck and pelvic protocols were 36.6 and 29.4 mGy, respectively. The total effective doses from the new head-and-neck and pelvic protocols were 1.7 and 8.2 mSv, respectively. The absorbed doses of lens for the new 200° and old 360° head-and-neck protocols were 3.8 and 59.4 mGy, respectively. The additional secondary cancer risk from daily CBCT might be up to 2.8%.
The new Varian CBCT provided volumetric information for image guidance with acceptable image quality and lower radiation dose. This imaging tool gave a better standard for patient daily setup verification.
The role of specific gut microbes in shaping body composition remains unclear. We transplanted fecal microbiota from adult female twin pairs discordant for obesity into germ-free mice fed low-fat ...mouse chow, as well as diets representing different levels of saturated fat and fruit and vegetable consumption typical of the U.S. diet. Increased total body and fat mass, as well as obesity-associated metabolic phenotypes, were transmissible with uncultured fecal communities and with their corresponding fecal bacterial culture collections. Cohousing mice harboring an obese twin's microbiota (Ob) with mice containing the lean co-twin's microbiota (Ln) prevented the development of increased body mass and obesity-associated metabolic phenotypes in Ob cage mates. Rescue correlated with invasion of specific members of Bacteroidetes from the Ln microbiota into Ob microbiota and was diet-dependent. These findings reveal transmissible, rapid, and modifiable effects of diet-by-microbiota interactions.
A fatal case associated with enterovirus D68 (EV-D68) infection affecting a 10-year-old boy was reported in Hong Kong in 2014. To examine if a new strain has emerged in Hong Kong, we sequenced the ...partial genome of the EV-D68 strain identified from the fatal case and the complete VP1, and partial 5'UTR and 2C sequences of nine additional EV-D68 strains isolated from patients in Hong Kong. Sequence analysis indicated that a cluster of strains including the previously recognized A2 strains should belong to a separate clade, clade D, which is further divided into subclades D1 and D2. Among the 10 EV-D68 strains, 7 (including the fatal case) belonged to the previously described, newly emerged subclade B3, 2 belonged to subclade B1, and 1 belonged to subclade D1. Three EV-D68 strains, each from subclades B1, B3, and D1, were selected for complete genome sequencing and recombination analysis. While no evidence of recombination was noted among local strains, interclade recombination was identified in subclade D2 strains detected in mainland China in 2008 with VP2 acquired from clade A. This study supports the reclassification of subclade A2 into clade D1, and demonstrates interclade recombination between clades A and D2 in EV-D68 strains from China.
Obesity is a major risk factor for cancers including hepatocellular carcinoma (HCC) that develops from a background of non-alcoholic fatty liver disease (NAFLD). Hypercholesterolemia is a common ...comorbidity of obesity. Although cholesterol biosynthesis mainly occurs in the liver, its role in HCC development of obese people remains obscure. Using high-fat high-carbohydrate diet-associated orthotopic and spontaneous NAFLD-HCC mouse models, we found that hepatic cholesterol accumulation in obesity selectively suppressed natural killer T (NKT) cell-mediated antitumor immunosurveillance. Transcriptome analysis of human liver revealed aberrant cholesterol metabolism and NKT cell dysfunction in NAFLD patients. Notably, cholesterol-lowering rosuvastatin restored NKT expansion and cytotoxicity to prevent obesogenic diet-promoted HCC development. Moreover, suppression of hepatic cholesterol biosynthesis by a mammalian target of rapamycin (mTOR) inhibitor vistusertib preceded tumor regression, which was abolished by NKT inactivation but not CD8
T cell depletion. Mechanistically, sterol regulatory element-binding protein 2 (SREBP2)-driven excessive cholesterol production from hepatocytes induced lipid peroxide accumulation and deficient cytotoxicity in NKT cells, which were supported by findings in people with obesity, NAFLD and NAFLD-HCC. This study highlights mTORC1/SREBP2/cholesterol-mediated NKT dysfunction in the tumor-promoting NAFLD liver microenvironment, providing intervention strategies that invigorating NKT cells to control HCC in the obesity epidemic.
On 2015 July 18, near perihelion at a heliocentric distance of 1.28 au, the Visible InfraRed Thermal Imaging Spectrometer (VIRTIS-M) on board the Rosetta spacecraft had the opportunity of observing ...dust activity in the inner coma with a view of the night side (shadowed side) of comet 67P/Churyumov-Gerasimenko. At the time of the measurements we present here, we observe a dust plume that originates on the far side of the nucleus. We are able to identify the approximate location of its source at the boundary between the Hapi and Anuket regions, and we find that it has been in darkness for some hours before the observation. Assuming that this time span is equal to the conductive time scale, we obtain a thermal inertia in the range 25–36 W K−1 m−2 s−1/2. These thermal inertia values can be used to verify with a 3D finite-element method (FEM) numerical code whether the surface and subsurface temperatures agree with the values found in the literature. We explored three different configurations: (1) a layer of water ice mixed with dust beneath a dust mantle of 5 mm with thermal inertia of 36 J m−2 K−1 s−0.5; (2) the same structure, but with thermal inertia of 100 J m−2 K−1 s−0.5; (3) an ice-dust mixture that is directly exposed. Of these three configurations, the first seems to be the most reasonable, both for the low thermal inertia and for the agreement with the surface and subsurface temperatures that have been found for the comet 67P/Churyumov-Gerasimenko. The spectral properties of the plume show that the visible dust color ranged from 16 ± 4.8%/100 nm to 13 ± 2.6%/100 nm, indicating that this plume has no detectable color gradient. The morphology of the plume can be classified as a narrow jet that has an estimated total ejected mass of between 6 and 19 tons when we assume size distribution indices between −2.5 and −3.
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