Πέμπτη 15 Φεβρουαρίου 2018
Association of clinicopathological features of melanoma with total naevus count and a history of dysplastic naevi: a cross-sectional retrospective study within an academic centre
Summary
Background
High naevus count (HNC) (≥ 50 naevi) and presence of dysplastic naevi (DN) are risk factors for malignant melanoma (MM); however, MMs also occur in patients with low naevus count (LNC) (< 50 naevi) and in patients without DN. Little is known about differences between MMs in these groups.
Aim
To characterize the clinicopathological differences between MMs in patients with HNC and those in patients with LNC, with or without biopsy-proven DN.
Methods
This was a cross-sectional retrospective chart review of 281 patients with MM seen between April 2013 and March 2014 at an academic pigmented lesion clinic (Boston, MA, USA).
Results
Patients with LNC MMs were diagnosed at an older age (51 vs. 41 years, P < 0.001, OR = 0.95, 95% CI 0.93–0.97), with more aggressive MM features, including greater Breslow thickness (1.1 vs. 0.8 mm, P = 0.01), more mitoses (2 vs. 1 mitoses/mm2, P < 0.001), lower rate of superficial spreading subtype (58 vs. 78%, P < 0.01, OR = 2.57, 95% CI 1.31–5.03) and higher MM stage (P < 0.001), compared to patients with HNC. Patients with DN had similar trends as those in patients with HNC described above, and in addition, were more likely to have a truncal MM (55 vs. 39%, P < 0.01, OR = 1.97, 95% CI 1.22–3.18) with less ulceration (13 vs. 29%, P < 0.01, OR = 0.36, 95% CI 0.19–0.71). Patients without DN were more likely to have a history of a non-MM skin cancer (32 vs. 19%, P = 0.01, OR = 0.49, 95% CI 0.28–0.85) and an amelanotic MM (33 vs 21%, P = 0.03, OR = 0.55, 95% CI 0.31–0.96).
Conclusions
Patients with LNC may develop MMs with more aggressive features at an older age than patients with HNC. A history of biopsy-proven DN reveals distinct MM differences compared to patients without DN.
Clinical Validation of a Predictive Model for the Presence of Cervical Lymph Node Metastasis in Papillary Thyroid Cancer [HEAD & NECK]
BACKGROUND AND PURPOSE:
Ultrasound is a standard technique to detect lymph node metastasis in papillary thyroid cancer. Cystic changes and microcalcifications are the most specific features of metastasis, but with low sensitivity. This prospective study compared the diagnostic accuracy of a predictive model for sonographic evaluation of lymph nodes relative to the radiologist's standard assessment in detecting papillary thyroid cancer metastasis in patients after thyroidectomy.
MATERIALS AND METHODS:Cervical lymph node sonographic images were reported by a radiologist (R method) per standard practice. The same images were independently evaluated by another radiologist using a sonographic predictive model (M method). A test was considered positive for metastasis if the R or M method suggested lymph node biopsy. The result of lymph node biopsy or surgical pathology was used as the reference standard. We estimated relative true-positive fraction and relative false-positive fraction using log-linear models for correlated binary data for the M method compared with the R method.
RESULTS:A total of 237 lymph nodes in 103 patients were evaluated. Our analysis of relative true-positive fraction and relative false-positive fraction included 54 nodes with pathologic results in which at least 1 method (R or M) was positive. The M method had a higher relative true-positive fraction of 1.46 (95% CI, 1.12–1.91; P = .006) and a lower relative false-positive fraction of 0.58 (95% CI, 0.36–0.92; P = .02) compared with the R method.
CONCLUSIONS:The sonographic predictive model outperformed the standard assessment to detect lymph node metastasis in patients with papillary thyroid cancer and may reduce unnecessary biopsies.
MRI with DWI for the Detection of Posttreatment Head and Neck Squamous Cell Carcinoma: Why Morphologic MRI Criteria Matter [HEAD & NECK]
BACKGROUND AND PURPOSE:
Although diffusion-weighted imaging combined with morphologic MRI (DWIMRI) is used to detect posttreatment recurrent and second primary head and neck squamous cell carcinoma, the diagnostic criteria used so far have not been clarified. We hypothesized that precise MRI criteria based on signal intensity patterns on T2 and contrast-enhanced T1 complement DWI and therefore improve the diagnostic performance of DWIMRI.
MATERIALS AND METHODS:We analyzed 1.5T MRI examinations of 100 consecutive patients treated with radiation therapy with or without additional surgery for head and neck squamous cell carcinoma. MRI examinations included morphologic sequences and DWI (b=0 and b=1000 s/mm2). Histology and follow-up served as the standard of reference. Two experienced readers, blinded to clinical/histologic/follow-up data, evaluated images according to clearly defined criteria for the diagnosis of recurrent head and neck squamous cell carcinoma/second primary head and neck squamous cell carcinoma occurring after treatment, post-radiation therapy inflammatory edema, and late fibrosis. DWI analysis included qualitative (visual) and quantitative evaluation with an ADC threshold.
RESULTS:Recurrent head and neck squamous cell carcinoma/second primary head and neck squamous cell carcinoma occurring after treatment was present in 36 patients, whereas 64 patients had post-radiation therapy lesions only. The Cohen for differentiating tumor from post-radiation therapy lesions with MRI and qualitative DWIMRI was 0.822 and 0.881, respectively. Mean ADCmean in recurrent head and neck squamous cell carcinoma/second primary head and neck squamous cell carcinoma occurring after treatment (1.097 ± 0.295 x 10–3 mm2/s) was significantly lower (P < .05) than in post-radiation therapy inflammatory edema (1.754 ± 0.343 x 10–3 mm2/s); however, it was similar to that in late fibrosis (0.987 ± 0.264 x 10–3 mm2/s, P > .05). Although ADCs were similar in tumors and late fibrosis, morphologic MRI criteria facilitated distinction between the 2 conditions. The sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios (95% CI) of DWIMRI with ADCmean < 1.22 x 10–3 mm2/s and precise MRI criteria were 92.1% (83.5–100.0), 95.4% (90.3–100.0), 92.1% (83.5–100.0), 95.4% (90.2–100.0), 19.9 (6.58–60.5), and 0.08 (0.03–0.24), respectively, indicating a good diagnostic performance to rule in and rule out disease.
CONCLUSIONS:Adding precise morphologic MRI criteria to quantitative DWI enables reproducible and accurate detection of recurrent head and neck squamous cell carcinoma/second primary head and neck squamous cell carcinoma occurring after treatment.
Modeling Early Postnatal Brain Growth and Development with CT: Changes in the Brain Radiodensity Histogram from Birth to 2 Years [PEDIATRICS]
BACKGROUND AND PURPOSE:
The majority of brain growth and development occur in the first 2 years of life. This study investigated these changes by analysis of the brain radiodensity histogram of head CT scans from the clinical population, 0–2 years of age.
MATERIALS AND METHODS:One hundred twenty consecutive head CTs with normal findings meeting the inclusion criteria from children from birth to 2 years were retrospectively identified from 3 different CT scan platforms. Histogram analysis was performed on brain-extracted images, and histogram mean, mode, full width at half maximum, skewness, kurtosis, and SD were correlated with subject age. The effects of scan platform were investigated. Normative curves were fitted by polynomial regression analysis.
RESULTS:Average total brain volume was 360 cm3 at birth, 948 cm3 at 1 year, and 1072 cm3 at 2 years. Total brain tissue density showed an 11% increase in mean density at 1 year and 19% at 2 years. Brain radiodensity histogram skewness was positive at birth, declining logarithmically in the first 200 days of life. The histogram kurtosis also decreased in the first 200 days to approach a normal distribution. Direct segmentation of CT images showed that changes in brain radiodensity histogram skewness correlated with, and can be explained by, a relative increase in gray matter volume and an increase in gray and white matter tissue density that occurs during this period of brain maturation.
CONCLUSIONS:Normative metrics of the brain radiodensity histogram derived from routine clinical head CT images can be used to develop a model of normal brain development.
Prediction of the Multisegment Clot Sign on Dynamic CT Angiography of Cardioembolic Stroke [ADULT BRAIN]
BACKGROUND AND PURPOSE:
The multisegment clot sign has been observed at the site of large-artery occlusion in patients with acute ischemic stroke. This study aimed to assess its occurrence rate and relationship with stroke etiologies in patients with acute intracranial large-artery occlusion.
MATERIALS AND METHODS:We included consecutive patients with acute ischemic stroke who had acute intracranial large-artery occlusion and underwent perfusion CT within 8 hours after stroke onset. The multisegment clot sign was assessed on dynamic CT angiography derived from perfusion CT. The stroke etiologies were defined by the international Trial of Org 10172 in Acute Stroke Treatment criteria. Poisson regression analyses and diagnostic testing were used to investigate the relationship between the multisegment clot sign and stroke etiologies.
RESULTS:Finally, 194 patients with intracranial large-artery occlusion were enrolled. According to the Trial of Org 10172 in Acute Stroke Treatment criteria, 110 (56.7%) patients were diagnosed with cardioembolism; 43 (22.2%), with large-artery atherosclerosis; and 41 (21.1%), with undetermined etiology. The multisegment clot sign was found in 74 (38%) patients. Poisson regression analysis showed that the presence of the multisegment clot sign was significantly higher in patients with cardioembolism than in those with large-artery atherosclerosis (52.7% versus 9.3%; prevalence ratio, 1.53; 95% confidence interval, 1.03–2.90; P = .037). For determined etiologies, the sensitivity, specificity, and positive and negative predictive values of the multisegment clot sign for predicting cardioembolism were 52.7%, 90.7%, 93.5%, and 42.9%, respectively.
CONCLUSIONS:The presence of the multisegment clot sign on dynamic CTA specifically indicates intracranial large-artery occlusion caused by an embolism from a cardiac source, which may be useful for acute management and secondary prevention of stroke.
A Patient Dose-Reduction Technique for Neuroendovascular Image-Guided Interventions: Image-Quality Comparison Study [PATIENT SAFETY]
BACKGROUND AND PURPOSE:
The ROI–dose-reduced intervention technique represents an extension of ROI fluoroscopy combining x-ray entrance skin dose reduction with spatially different recursive temporal filtering to reduce excessive image noise in the dose-reduced periphery in real-time. The aim of our study was to compare the image quality of simulated neurointerventions with regular and reduced radiation doses using a standard flat panel detector system.
MATERIALS AND METHODS:Ten 3D-printed intracranial aneurysm models were generated on the basis of a single patient vasculature derived from intracranial DSA and CTA. The incident dose to each model was reduced using a 0.7-mm-thick copper attenuator with a circular ROI hole (10-mm diameter) in the middle mounted inside the Infinix C-arm. Each model was treated twice with a primary coiling intervention using ROI-dose-reduced intervention and regular-dose intervention protocols. Eighty images acquired at various intervention stages were shown twice to 2 neurointerventionalists who independently scored imaging qualities (visibility of aneurysm-parent vessel morphology, associated vessels, and/or devices used). Dose-reduction measurements were performed using an ionization chamber.
RESULTS:A total integral dose reduction of 62% per frame was achieved. The mean scores for regular-dose intervention and ROI dose-reduced intervention images did not differ significantly, suggesting similar image quality. Overall intrarater agreement for all scored criteria was substantial (Kendall = 0.62887; P < .001). Overall interrater agreement for all criteria was fair ( = 0.2816; 95% CI, 0.2060–0.3571).
CONCLUSIONS:Substantial dose reduction (62%) with a live peripheral image was achieved without compromising feature visibility during neuroendovascular interventions.
7T Brain MRS in HIV Infection: Correlation with Cognitive Impairment and Performance on Neuropsychological Tests [ADULT BRAIN]
BACKGROUND AND PURPOSE:
Validated neuroimaging markers of HIV-associated neurocognitive disorder in patients on antiretroviral therapy are urgently needed for clinical trials. The purpose of this study was to explore the relationship between cognitive impairment and brain metabolism in older subjects with HIV infection. It was hypothesized that MR spectroscopy measurements related to neuronal health and function (particularly N-acetylaspartate and glutamate) would be lower in HIV-positive subjects with worse cognitive performance.
MATERIALS AND METHODS:Forty-five HIV-positive patients (mean age, 58.9 ± 5.3 years; 33 men) underwent detailed neuropsychological testing and brain MR spectroscopy at 7T. Twenty-four subjects were classified as having asymptomatic cognitive impairment, and 21 were classified as having symptomatic cognitive impairment. Single-voxel proton MR spectra were acquired from 5 brain regions and quantified using LCModel software. Brain metabolites and neuropsychological test results were compared using nonparametric statistics and Pearson correlation coefficients.
RESULTS:Differences in brain metabolites were found between symptomatic and asymptomatic subjects, with the main findings being lower measures of N-acetylaspartate in the frontal white matter, posterior cingulate cortex, and precuneus. In the precuneus, glutamate was also lower in the symptomatic group. In the frontal white matter, precuneus, and posterior cingulate cortex, NAA and glutamate measurements showed significant positive correlation with better performance on neuropsychological tests.
CONCLUSIONS:Compared with asymptomatic subjects, symptomatic HIV-positive subjects had lower levels of NAA and glutamate, most notably in the frontal white matter, which also correlated with performance on neuropsychological tests. High-field MR spectroscopy offers insight into the pathophysiology associated with cognitive impairment in HIV and may be useful as a quantitative outcome measure in future treatment trials.
MRI Features of Aquaporin-4 Antibody-Positive Longitudinally Extensive Transverse Myelitis: Insights into the Diagnosis of Neuromyelitis Optica Spectrum Disorders [SPINE]
BACKGROUND AND PURPOSE:
Longitudinally extensive transverse myelitis is a well-documented spinal manifestation of neuromyelitis optica spectrum disorders, however, other forms of nontumorous myelopathy can also manifest as longitudinally extensive transverse myelitis. Our aim was to evaluate the MR imaging features of aquaporin-4 antibody–positive longitudinally extensive transverse myelitis, which is strongly associated with neuromyelitis optica spectrum disorders.
MATERIALS AND METHODS:We evaluated cervicomedullary junction involvement, cord expansion ratios, bright spotty lesions, the number of involved segments, skipped lesions, enhancement patterns, and axial distribution patterns using spinal MR imaging of 41 patients with longitudinally extensive transverse myelitis who underwent aquaporin-4 antibody testing. Univariate logistic regression analysis was performed to identify factors associated with aquaporin-4 antibody seropositivity, which were then used to develop a scoring system for diagnosing aquaporin-4 antibody–positive longitudinally extensive transverse myelitis. Interrater reliability for cord expansion ratio measurement and bright spotty lesions was determined using intraclass correlation coefficients and values, respectively.
RESULTS:Fifteen patients with longitudinally extensive transverse myelitis were aquaporin-4 antibody–positive. Sex (female), cervicomedullary junction involvement, a cord expansion ratio of >1.4, and bright spotty lesions were significantly associated with aquaporin-4 antibody seropositivity. The sensitivity and specificity of the scoring system were 73.3% and 96.2%, respectively. The interclass correlation value for the cord expansion ratio was 0.78, and the value for bright spotty lesions was 0.61.
CONCLUSIONS:Our scoring system, based on cervicomedullary junction involvement, higher cord expansion ratio, bright spotty lesions, and female sex, can facilitate the timely diagnosis of neuromyelitis optica spectrum disorders.
Wnt7a promotes wound healing by regulation of angiogenesis and inflammation: Issues on diabetes and obesity
Diabetic skin heals wounds poorly. Though obesity is the common risk factor of diabetes mellitus, few studies have investigated its effects on wound healing.
Reply: lymph stasis promotes tumor growth
Our study suggested that surgical damage of the lymphatic system promotes tumor progression via impaired immune response [1]. However, as pointed out by Valerio et al., lymph stasis is likely to induce immune stasis, resulting in not only enhanced tumor growth but also tumor generation [2,3]. In addition, bacterial infections often develop in the lymphedematous lesion, which would be mainly caused by immune suppression due to lymph stasis [2].
Lymph stasis promotes tumor growth
We have read with great interest the paper by Nakamura and colleagues [1] demonstrating that surgical damage to the lymphatic system promotes skin cancer growth by impairing adaptive immune response.
Proteins involved in the antioxidant and inflammatory response in rutin-treated human skin fibroblasts exposed to UVA or UVB irradiation
The proteome is the complete set of proteins expressed by an organism, including the post-translational modifications, is characteristic for cell type, its age, stage of differentiation and maturation, as well as environmental conditions [1]. The composition of this set of proteins is modified at any given time by various cell activities such as gene transcription and de novo biosynthesis of proteins, as well as by the degradation of old, damaged, inactive or just unnecessary molecules. At physiological conditions, the rate of protein synthesis and degradation should be balanced and adept to sustaining cell growth and function.
Effects of growth agents and mercury on several herbs
Abstract
The paper discussed the effects of growth agents and mercury on the growth of four herb species subjected to a pot experiment: Aloe vera, Setcreasea purpurea, Chlorophytum comosum, and Oxalis corniculata. We determined the height and biomass production of selected plants treated with different growth agents and different concentrations of mercury solutions. We evaluated the relative growth rate (RGR) of the experimental plants. The aim of the study was to explore potential novel solutions to the shortcoming of the low speed of phytoremediation. The results showed that the upper parts of Aloe vera and Chlorophytum comosum had the fastest growth in the treatment with water only. In contrast, the upper parts of Setcreasea purpurea grew most intensely after the treatment with Lvyebao Fertilizer, whereas the aboveground parts of Oxalis corniculata had the fastest growth after the application of water and the occasional use of Green Cake Fertilizer. In addition, the tolerance to mercury of Oxalis corniculata was the strongest, whereas that of Chlorophytum comosum was the lowest among the species investigated.
Exposure marker discovery of di(isononyl)cyclohexane-1,2-dicarboxylate using two mass spectrometry-based metabolite profiling data processing methods
Abstract
Di(isononyl)cyclohexane-1,2-dicarboxylate (DINCH) is a plasticizer used in polyvinyl chloride (PVC) products, such as toys and food packaging. Because the use of DINCH is on the rise, the risk of human exposure to this chemical may likewise increase. Discovering markers for assessing human chemical exposure is difficult because the metabolism of chemicals within humans is complex. In this study, two mass spectrometry (MS)-based metabolite profiling data processing methods, the mass defect filter (MDF) method and the signal mining algorithm with isotope tracing (SMAIT) method, were used for DINCH metabolite discovery, and 110 and 18 potential DINCH metabolite signal candidates were discovered, respectively, from in vitro DINCH incubation samples. Of these, the 21 signals were validated as tentative exposure marker signals in a rat model. Interestingly, the two methods generated rather different sets of DINCH exposure markers. Five of the 21 tentative exposure marker signals were verified as the probable DINCH structure-related metabolite signals based on their MS/MS product ion profiles. These five signals were detected in at least one human urine sample. Of the five probable DINCH structure-related metabolite signals, two novel signals might be suitable exposure markers that should be further investigated for their application in human DINCH exposure assessments. These observations indicate that the MDF and SMAIT methods may be used to discover a relatively different set of potential DINCH exposure markers.
Modulatory role of GSTT1 and GSTM1 in Punjabi agricultural workers exposed to pesticides
Abstract
Glutathione S-transferases are important detoxification enzymes involved in the metabolism of endogenous as well as exogenous compounds. Individuals differ in metabolic capacity due to inherited genetic variations. Due to the polymorphism exhibited by GSTT1 and GSTM1 that results in the complete loss of function, the present study was aimed towards the determination of the frequency distribution of GSTT1 and GSTM1 in agricultural workers in Punjab, India. The study aimed to investigate their contribution in susceptibility to increased disease risk. A total of 513 subjects were included in this study, out of which 250 were agriculture workers and 263 were non-exposed occupationally. GSTT1 and GSTM1 null-genotype distribution was analyzed through multiplex-PCR method. Complete gene deletion in either of the genes was strongly associated with an increased risk (OR = 1.8; 95% CI = 1.3–2.6; p < 0.0008) of DNA/cytogenetic damage, cancer, infertility, and many other serious health effects. Therefore, homozygous deletion in GSTT1 or GSTM1 could play a modulatory role in health of workers with long-term exposure to pesticides.
Recovery and characterization of proteins from pangas ( Pangasius pangasius ) processing waste obtained through pH shift processing
Abstract
Study was conducted to recover proteins from pangas (Pangasius pangasius) processing waste (fillet frames) using pH shift method and to characterize the recovered isolates. pH 2.0 from acidic range and pH 13.0 from alkaline range were found to have maximum protein recovery (p < 0.05). During the recovery process, acidic pH (pH 2.0) was found to have minimal effect on proteins resulting in more stable isolates and strong protein gels. Alkaline pH (pH 13.0) caused protein denaturation resulting in less stable proteins and poor gel network. Both acidic and alkaline-aided processing caused significant (p < 0.05) reductions in total lipid, myoglobin, and pigment content thus by resulting in whiter protein isolates and gels. The content of total essential amino acids increased during pH shift processing, indicating the enrichment of essential amino acids. No microbial counts were detected in any of the isolates prepared using acid and alkaline extraction methods. pH shift processing was found to be promising in the utilization of fish processing waste for the recovery of functional proteins from pangas processing waste thus by reducing the supply demand gap as well pollution problems.
High-density lipoprotein (HDL) promotes angiogenesis via S1P3-dependent VEGFR2 activation
Abstract
High-density lipoprotein (HDL) has previously been shown to promote angiogenesis. However, the mechanisms by which HDL enhances the formation of blood vessels remain to be defined. To address this, the effects of HDL on the proliferation, transwell migration and tube formation of human umbilical vein endothelial cells were investigated. By examining the abundance and phosphorylation (i.e., activation) of the vascular endothelial growth factor receptor VEGFR2 and modulating the activity of the sphingosine-1 phosphate receptors S1P1–3 and VEGFR2, we characterized mechanisms controlling angiogenic responses in response to HDL exposure. Here, we report that HDL dose-dependently increased endothelial proliferation, migration and tube formation. These events were in association with increased VEGFR2 abundance and rapid VEGFR2 phosphorylation at Tyr1054/Tyr1059 and Tyr1175 residues in response to HDL. Blockade of VEGFR2 activation by the VEGFR2 inhibitor SU1498 markedly abrogated the pro-angiogenic capacity of HDL. Moreover, the S1P3 inhibitor suramin prevented VEGFR2 expression and abolished endothelial migration and tube formation, while the S1P1 agonist CYM-5442 and the S1P2 inhibitor JTE-013 had no effect. Last, the role of S1P3 was further confirmed in regulation of S1P-induced endothelial proliferation, migration and tube formation via up-regulation and activation of VEGFR2. Together, these findings argue that HDL promotes angiogenesis via S1P3-dependent up-regulation and activation of VEGFR2 and also suggest that the S1P–S1P3–VEGFR2 signaling cascades as a novel target for HDL-modulating therapy implicated in vascular remodeling and functional recovery in atherosclerotic diseases such as myocardial infarction and ischemic stroke.
Removal of tetracyclines, sulfonamides, and quinolones by industrial-scale composting and anaerobic digestion processes
Abstract
This study evaluated and compared the removal of antibiotics by industrial-scale composting and anaerobic digestion at different seasons. Twenty compounds belonged to three classes of widely used veterinary antibiotics (i.e., tetracyclines, sulfonamides, and quinolones) were investigated. Results show that of the three groups of antibiotics, tetracyclines were dominant in swine feces and poorly removed by anaerobic digestion with significant accumulation in biosolids, particularly in winter. Compared to that in winter, a much more effective removal (> 97%) by anaerobic digestion was observed for sulfonamides in summer. By contrast, quinolones were the least abundant antibiotics in swine feces and exhibited a higher removal by anaerobic digestion in winter than in summer. The overall removal of antibiotics by aerobic composting could be more than 90% in either winter or summer. Nevertheless, compost products from livestock farms in Beijing contained much higher antibiotics than commercial organic fertilizers. Thus, industrial composting standards should be strictly applied to livestock farms to further remove antibiotics and produce high quality organic fertilizer.
Simultaneous immobilization of cadmium and lead in contaminated soils by hybrid bio-nanocomposites of fungal hyphae and nano-hydroxyapatites
Abstract
Self-aggregation of bulk nano-hydroxyapatites (n-HAPs) undermines their immobilization efficiencies of heavy metals in the contaminated soils. Here, the low-cost, easily obtained, and environment-friendly filamentous fungi have been introduced for the bio-matrices of the hybrid bio-nanocomposites to potentially solve such problem of n-HAPs. According to SEM, TEM, XRD, and FT-IR analyses, n-HAPs were successfully coated onto the fungal hyphae and their self-aggregation was improved. The immobilization efficiencies of diethylene-triamine-pentaacetic acid (DTPA)-extractable Cd and Pb in the contaminated soils by the bio-nanocomposites were individually one to four times of that by n-HAPs or the fungal hyphae. Moreover, the Aspergillus niger-based bio-nanocomposite (ANHP) was superior to the Penicillium Chrysogenum F1-based bio-nanocomposite (PCHP) in immobilization of Cd and Pb in the contaminated soils. In addition, the results of XRD showed that one of the potential mechanisms of metal immobilization by the hybrid bio-nanocomposites was dissolution of n-HAPs followed by precipitation of new metal phosphate minerals. Our results suggest that the hybrid bio-nanocomposite (ANHP) can be recognized as a promising soil amendment candidate for effective remediation on the soils simultaneously contaminated by Cd and Pb.
Influence of Mn 2+ ions on the corrosion mechanism of lead-based anodes and the generation of heavy metal anode slime in zinc sulfate electrolyte
Abstract
The influence of Mn2+ ions on the generation of heavy metal anode slime during zinc electrolysis industry was extensively investigated using several electrochemical methods, electron microscope technologies, and particle size analysis. Results showed that the Mn2+ could obviously promote oxygen evolution reaction (OER) and thereby weaken oxidation efficiency of Mn2+ (ηMnO2) and dissolution of Pb2+. The significant improvement in kinetic parameters for OER was found in electrolytes of 1 and 3 g/L Mn2+, but became unstable as the Mn2+ concentration increased to 10 g/L. This result was correlated with much different properties of oxide layers that its changes of microstructure are involved in, since it confirmed that the positive role of compact oxide layers in contributing to high corrosion resistance and activity for OER, but excessive Mn2+, resulted in its micromorphology of overthickness and instability. Such differences resulted from the effect of the Mn2+ concentration fluctuation on kinetic rates of the nucleation growth process. The formation and adsorption of intermediate MnO2–OHads identified as the controlled step for Mn2+ catalyzing OER was also recommended. The generation mechanism of anode slime was found to be changed in essence due to varying Mn2+ concentrations. In electrolyte of 1 g/L Mn2+, results revealed that the root cause of excessive small suspended anode slime (around 20 μm) was the change of the initial pathway of Mn2+ electro-oxidation, whereas, it showed great improvement in the settling performance as the Mn2+ concentration was increased to 10 g/L. Considering the potential of optimizing Mn2+ concentrations as a cleaner approach to control anode slime, deepening the understanding of the impact mechanism of Mn2+ can provide new insights into intervention in the generation of anode slime.
Association of Internet Researchers (AoIR) Roundtable Summary: Artificial Intelligence and the Good Society Workshop Proceedings
Abstract
This article is based on a roundtable held at the Association of Internet Researchers (AoIR) annual conference in 2017, in Tartu, Estonia. The roundtable was organized by the Oxford Internet Institute's (OII) Digital Ethics Lab (DELab). It was entitled "Artificial Intelligence and the Good Society". It brought together four scholars—Michael Zimmer, Stine Lomborg, Ben Zevenbergen, and Corinne Cath—to discuss the promises and perils of artificial intelligence (AI), in particular what ethical frameworks are needed to guide AI's rapid development and increased use in societies. The paper covers three case studies. They give a distinct overview of the ethical issues raised by the use of AI at different levels of analysis: top-down application of AI, bottom-up use of AI, and how academics and governments have reacted to these new challenges. From the case studies, four areas emerged. They represent some of the most topical ethical questions related to AI: (1) its uses, (2) its users, (3) its designers, and (4) the data that fuel it. Each of them provided a specific subset of ethical concerns that need further investigation. In conclusion, three recommendations are formulated for researchers and regulators to ensure the AI has a net-positive impact on society.
Dissolved organic matter distribution and its association with colloidal aluminum and iron in the Selenga River Basin from Ulaanbaatar to Lake Baikal
Abstract
The Selenga River Basin (Mongolia and Russia) has suffered from heavy metal contamination by placer gold mining and urban activities in recent decades. The objectives of this study were to provide the first distribution data of dissolved organic matter (DOM) and humic substances (HS) in this data-scarce region, and to investigate their association with dissolved and colloidal metals. Two sampling campaigns were conducted in August of 2013 and 2014. A constant proportion of HS (%HS; coefficient of variation of 2%) was observed from the headwater of Tuul River to the end of the delta before Lake Baikal, spanning > 1000 km in distance. The relationships were determined as [HS] = 0.643 × [DOM] (R2 = 0.996, P < 0.001), and this value (%HS = 64.3) is recommended as an input parameter for metal speciation modeling based on samples collected from the rivers. The DOM and metal (Al and Fe) concentrations in samples doubled through the Zaamar Goldfield mining area, but the influence was mitigated by mixing with the larger Orkhon River, which has better water quality. Metals were mainly present as colloids and had a strong positive correlation with DOM (Al r = 0.81, P < 0.01; Fe r = 0.61, P < 0.01), suggesting that DOM sustains colloidal Al and Fe in solution and they are co-transported in the Selenga River Basin. Land use changes affect water quality and metal speciation and therefore have major implications for the fate of metals.
Fetal exposure markers of dioxins and dioxin-like PCBs
Abstract
Fetal exposure to polychlorinated biphenyls (PCBs), polychlorinated-p-dibenzodioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) have been associated with a number of adverse health outcomes. Although the placenta acts as a barrier between the mother and the fetus, these contaminants transfer through the placenta exposing the fetus. Several studies have investigated placental transfer, but few have assessed the co-variation among these contaminants. Maternal blood, cord blood, and cord tissue were collected from 41 Japanese mother-infant pairs and analyzed for dioxin-like PCBs and PCDD/Fs. Hierarchical cluster analysis followed by principal component analysis were used to assess the co-variation. Two stable clusters of dioxin-like PCBs were found in maternal and cord blood. One cluster of low/medium chlorinated dioxin-like PCBs was present in all three matrices with 2,3',4,4',5-PeCB(#118) and 3,3',4,4',5-PeCB(#126) explaining the majority of the clusters' variances. Medium/high chlorinated dioxin-like PCBs clustered in maternal blood and cord blood but not in cord tissue. 2,3,4,4',5-PeCB(#114) and 2,3,3',4,4',5,5'-HpCB(#189) explained the majority of the clusters' variances. There was a substantial correlation between the sum of dioxin-like PCBs and total PCDD/F in all three matrices. The sum of the four suggested PCBs plus 3,3',4,4'-TeCB(#77) correlated well with total PCDD/F in all three matrices. Apart from the dioxin-like PCBs, little co-variation existed among the studied contaminants. The five PCBs can be used as fetal exposure markers for dioxin and dioxin-like PCBs in maternal and cord blood respectively. In cord tissue, more higher chlorinated dioxin-like PCBs need to be measured as well.
How can water quality be improved when the urban waste water directive has been fulfilled? A case study of the Lot river (France)
Abstract
The Lot river, a major tributary of the downstream Garonne river, the largest river on the Northern side of the Pyrenees Mountains, was intensively studied in the 1970s. A pioneering program called "Lot Rivière Claire" provided a diagnosis of water quality at the scale of the whole watershed and proposed an ambitious program to manage nutrient pollution and eutrophication largely caused by urban wastewater releases. Later on, the implementation of European directives from 1991 to 2000 resulted in the nearly complete treatment of point sources of pollution in spite of a doubling of the basin's population. At the outlet of the Lot river, ammonium and phosphate contamination which respectively peaked to 1 mg N-NH4 L−1 and 0.3 mg P-PO4 L−1 in the 1980s returned to much lower levels in recent years (0.06 mg N-NH4 L−1 and 0.02 mg P-PO4 L−1), a reduction by a factor 15. However, during this time, nitrate contamination has regularly increased since the 1980s, from 0.5 to 1.2 mg N-NO3 L−1 in average, owing to the intensification of agriculture and livestock farming. Application of the Riverstrahler model allowed us to simulate the water quality of the Lot drainage network for the 2002–2014 period. We showed that, with respect to algal requirements, phosphorus and silica are well balanced, but nitrogen remains largely in excess over phosphorus and silica. This imbalance can be problematic for the ecological status of the water bodies. Using the model, for simulating various scenarios of watershed management, we showed that improvement of urban wastewater treatment would not result in any significant change in the river's water quality. Even though arable land occupies a rather limited fraction of the watershed area, only the adoption of better farming practices or more radical changes in the agro-food system could reverse the trend of increasing nitrate contamination.
Mental Health and Patient Satisfaction With Outcomes of Rhinoplasty
This case-control study compares satisfaction with the functional outcomes of rhinoplasty between patients with normal mental well-being and those with poor mental well-being.
Technique to Repair Total Septal Perforation With a Pericranial Flap
This Surgical Pearl provides step-by-step guidance on how to rebuild a new nasal septum, highlighting key learning points and potential operative pitfalls.
Three faces of responsibility? Comments on responsibility from the margins
Abstract
This rich and wide-ranging book defends a "tripartite theory" of responsibility. The general thesis is that responsibility-responses (understood as families of sentimental reactions to others in their capacity as actors or holders of particular attitudes) fall into three overlapping categories, each of which presumes distinct agential capacities. On the basis of a close examination of various sorts of marginal agency, these capacities are said to be independent and ground what deserves to be called distinct types or "faces" of responsibility. The first face, attributability, depends on a capacity for character, answerability on a capacity for judgment, and accountability on a capacity for "regard". This commentary questions the theory's account of the relations among the types of responsibility, and its attempt to ground responsibility-responses in qualities of "will".
The effect of pyrazolyl substituents on the photophysical and photochemical properties of pyrazine derivatives
Abstract
The reaction of 2,5-dibromopyrazine with N-Lithium pyrazolate in a 1:2 ratio leads to a mixture of 2-bromo-5-(1H-pyrazol-1-yl)pyrazine (I) and 2,5-di(1H-pyrazol-1-yl)pyrazine (II). The structures of I and II are highly planar. Two absorption bands can be observed for the compounds in the UV-Vis region, having ε in the order of 104 M−1 cm−1. TD-DFT computed results support the nature of the lower energy absorptions as πpyrazine![[RIGHTWARDS ARROW]](https://lh3.googleusercontent.com/blogger_img_proxy/AEn0k_syw1VOICEOWVQ2nV3-seMzVXdNUnN8HPNdg2m34XobkGAGZ8Hw_ULmeNKhlJEnNCxXNSbaR93biyvmz9bwp7LGgm1rsfk-1kvE_8Z_vadSDpL-WbV4KrzOgTPsxc_OJLSdyOWiVa7M3jgU=s0-d)
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Correction to: Air quality and acute myocardial infarction in adults during the 2016 Hangzhou G20 summit
Abstract
Unfortunately, the original publication of this paper contains a mistake. The correct name of the 1st Author is Ming-Wei Wang.
Computerized tomographic evaluation of supraorbital notches and foramen in patients with frontal migraine headaches and correlation with clinical symptoms
To correlate the location and size of supraorbital notches (SON) and foramen (SOF) with migraine headache symptoms in a migraine patient population.
A fast and improved method of rapid prototyping for ear prosthesis using portable 3d laser scanner
Conventionally, facial prostheses are developed using wax or clay sculpted patterns. However, recent technological advancements in rapid prototyping systems have shown noteworthy advantages in fabricating facial prostheses that contrast traditional methods. Selective laser sintering technology is an example of this type of technological innovation. This technology can be used as an alternative method in the fabrication of wax patterns for a partial auricular prosthesis. The utilization of this advanced approach greatly reduces manual laboratory steps by directly creating the wax auricular pattern.
Biodurability of poly implant prothèse (PIP) breast implants: a prospective analysis of 1028 prostheses in 514 patients.
Poly Implant Prothèse (PIP) was a company that manufactured substandard breast implants using cheaper non-medical grade silicon. Around 40,000 women in the UK are thought to have PIP implants inserted(1). The advice for Women in Wales is: seek clinical advice prior to requesting routine removal. If there is clinical need, the National Health Service (NHS) in Wales funds removal and replacement of PIP breast implants inserted privately. This is in contrast to NHS in England where only PIP implants placed on the NHS are replaced.
Total penile reconstruction: a systematic review
BackgroundPhalloplasty poses a unique challenge to the plastic and reconstructive surgeon. The development of advanced microsurgical techniques has greatly augmented the range of surgical approaches available.MethodsA systematic review of the MEDLINE and Cochrane databases was performed to identify clinical studies of total penile reconstruction published within the last 10 years using the search algorithm: "(phallus or penis or penile) and (reconstruction or phalloplasty or transplant)".ResultsThe primary literature search retrieved 1400 articles.
Efficacy of a novel strategy for poststernotomy deep sternal infection after thoracic aorta replacement using a prosthetic graft
Poststernotomy deep sternal wound infections are persistent and occasionally fatal, especially in cases involving prosthetic grafts, because of its complicated structure and virtual impossibility of removal. We aimed to verify the influence of cooperation with plastic surgeons and our novel strategy for treating deep sternal wound infection after aortic replacement on cardiovascular surgery outcomes.
A retrospective study of closed extension block pinning for mallet fractures: analysis of predictors of postoperative range of motion
Extension block pinning is a simple and reliable technique for mallet fractures, but poor results are sometimes obtained. The predictors of postoperative range of motion after extension block pinning of mallet fingers were investigated.
Factors predicting health-related quality of life following necrotizing fasciitis
Necrotizing fasciitis (NF) is a debilitating soft tissue infection that results in disfiguring scars and often amputations. While mortality rates have improved, long-term outcomes in survivors of NF are poorly understood.
Superficial acral fibromyxoma in the heel with new vascular features on dermoscopy
Superficial acral fibromyxoma (SAFM) is an uncommon mesencyhmal soft tissue tumor with a predilection for the acral extremites and nail bed involvement. SAFM is diagnosed with clinicopathological and immunohistochemical examination. Awareness of this rare tumor is important because of amounts of benign and malignant neoplasms. We report a case of SAFM in a rare localization in the heel with a new entity on dermoscopy.
Histological Immune Response Patterns in Sentinel Lymph Nodes Involved by Metastatic Melanoma and Prognostic Significance
Aims
To further characterize the micromorphometric immunological pattern to metastatic melanoma in SLN biopsies and completion lymph node (CLN) dissections and their relation to 5-year overall survival.
Methods
Retrospective cohort of 49 patients from 1996 to 2005 with a positive SLN who underwent CLN dissection were studied. Micromorphometric characteristics included: follicular center count per profile (FCC), sinus histiocytosis, metastatic size, tumor infiltrating lymphocytes (intranodal), paracortial dendritic cells, germinal center reaction, and morphology. Comparison of Kaplan-Meier survival curves used the exact log rank statistic.
Results
In the high FCC (n5-51) versus the low FCC (n<5) lymph nodes, a delayed separation occurred at 3 years, with 5-year overall survival rates being 73% versus 54% in the high and low FCC groups respectively. Improved survival up to 3-years was also noted in CLDs that demonstrated a higher FCC when compared to the prior SLN. Patients with metastatic deposits >2 mm had significantly lower 5-year survival (both <0.001).
Conclusions
Nodal micromorphometric features (i.e. FCC) are likely related to host immune response to metastasis. Quantitative evaluation of lymphoid follicular centers could provide valuable prognostic information to help to stratify patients.
Purification and molecular characterization of a Metschnikowia saccharicola killer toxin lethal to a crab pathogenic yeast
Abstract
The marine yeast strain Metschnikowia saccharicola DD21–2, isolated from sediments in the Yalu River, produces a killer toxin with a lethal effect on Metschnikowia bicuspidate strain WCY, a pathogenic yeast strain that infects crabs. In this study, the killer toxin was purified and characterized. After sequential purification, the purity of the killer toxin was increased 72.2-fold over the purity of the yeast cell culture supernatant. The molecular weight of the purified killer toxin was 47.0 kDa. The optimal pH and temperature for killing activity were 5.5 and 16°C, respectively. The killing activity was stable over a pH range of 4.0 to 6.5 and temperature range of 0 to 40°C. The purified killer toxin was only effective against toxin-sensitive integral cells and had no killing effect on the protoplasts of toxin-sensitive cells. When exerting the killing effect, the toxin bind to a cell wall receptor of the treated strain, disrupted cell wall integrity and eventually caused death. The amino acid sequence identified by MS indicated that the purified killer toxin might be a protein kinase, but did not show β-1,3-glucanase activity, consistent with the laminarin hydrolysis results. These findings provide a basis for disease prevention and control in marine aquaculture.A Semi-Empirical Approach to the Determination of Daily Erythemal Doses
Abstract
The maintenance of ground-based instruments to measure the incidence of ultraviolet radiation (UVR) from the Sun demands strict and well-developed procedures. A piece of equipment can be out of service for a couple of weeks or months for calibration, repair, or even the improvement of the facilities where it has been set up. However, the replacement of an instrument in such circumstances can be logistically and financially prohibitive. On the other hand, the lack of data can jeopardize a long-term experiment. In this study, we introduce a semi-empirical approach to the determination of the theoretical daily erythemal dose (DEDt) for periods of instrumental absence in a tropical site. The approach is based on 5-years of ground-based measurements of daily erythemal dose (DED) linearly correlated with parameters of total ozone column (TOC) and reflectivity (RPC) from the Ozone Monitoring Instrument (OMI), and the cosine of solar zenith angle at noon (SZAn). Seventeen months of missing ground-based data were replaced with DEDt, leading to a complete 5-year series of data. The lowest and the highest values of typical DED were 2411 ± 322 J/m2 (1σ) (winter) and 5263 ± 997 J/m2 (summer). The monthly integrated erythemal dose (mED) varied from 59 kJ/m2 (winter) to 162 kJ/m2 (summer). Both of them depended mainly on cos(SZAn) and RPC. The 12-month integrated erythemal dose (12-ED) ranged from 1350 kJ/m2 to 1546 kJ/m2, but it can depend significantly on other atmospheric parameter (maybe aerosols) not explicitly considered here.
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Industry Corner: Perspectives and Controversies: Restoration of conformation of mutant p53Restoration of conformation of mutant p53
p53 mutationsp53 conformation restorationhigh grade serous ovarian cancertargeted therapy
Artemisinin Therapy for Malaria in Hemoglobinopathies: A Systematic Review
Abstract
Artemisinin derivatives are widely used antimalarial drugs. There is some evidence from in vitro, animal and clinical studies that hemoglobinopathies may alter their disposition and antimalarial activity. This review assesses relevant data in α-thalassemia, sickle cell disease (SCD), β-thalassemia and hemoglobin E. There is no convincing evidence that the disposition of artemisinin drugs is affected by hemoglobinopathies. Although in vitro studies indicate that Plasmodium falciparum cultured in thalassemic erythrocytes is relatively resistant to the artemisinin derivatives, mean 50% inhibitory concentrations (IC50s) are much lower than in vivo plasma concentrations after recommended treatment doses. Since IC50s are not increased in P. falciparum cultures using SCD erythrocytes, delayed post-treatment parasite clearance in SCD may reflect hyposplenism. As there have been no clinical studies suggesting that hemoglobinopathies significantly attenuate the efficacy of artemisinin combination therapy (ACT) in uncomplicated malaria, recommended artemisinin doses as part of ACT remain appropriate in this patient group.Reply to Magréault et al
To the Editor—We thank Magréault and colleagues for their comments [1] that allow us to better specify our approach to colistin plasma determination.
Colistin Pharmacokinetics in Pediatrics
To the Editor—Mesini et al have recently published an article relying on colistin area under the time-concentration curve (AUC) in children, leading to dosing regimen recommendations [1]. Measured colistin concentrations are surprisingly high and uncontrolled degradation of the infused prodrug (colistin methanesulfonate [CMS]) may be suspected, but this is impossible to assess as CMS concentrations are not reported. Yet there is no doubt that AUC estimate based on 2 concentrations is inappropriate.
Dose Suggestions for Intravenous Colistin in Pediatric Patients: Caution Required
To the Editor—Mesini et al reported plasma concentrations of colistin in 7 pediatric patients (aged 46 days to 13 years) who were receiving intravenously the inactive prodrug colistimethate; across all patients, plasma colistin concentrations were measured on 13 occasions [1]. That report has been the subject of critical appraisal by Magréault et al [2], who expressed substantial concerns about the magnitude of the plasma colistin concentrations reported and the pharmacokinetic analysis conducted by Mesini and coworkers. I agree with Magréault et al and amplify their comments. I have very substantial concerns about the dosing recommendations implicitly presented in the report of Mesini and coworkers.
Breast Implant Q Fever as a Source of In-Hospital Transmission
Abstract
Herein, we describe the first case of mammary implant infection caused by Coxiella burnetii, resulting in delayed diagnosis and treatment and an in-hospital cross-transmission of Q fever to medical personnel.Immediate Antiretroviral Therapy Decreases Mortality Among Patients With High CD4 Counts in China: A Nationwide, Retrospective Cohort Study
Abstract
Background
Clinical trials have demonstrated that immediate initiation of antiretroviral therapy (ART) reduces AIDS-related morbidity and mortality. We tested the hypothesis that initiating ART ≤30 days after human immunodeficiency virus (HIV) diagnosis would be associated with reduced mortality among people living with HIV (PLWH) with CD4 counts >500 cells/μL. Methods
PLWH enrolled in the Chinese National HIV Information System between January 2012 and June 2014 with CD4 counts >500 cells/μL were followed for 12 months. Cox proportional hazards model was used to determine hazard ratios (HRs) for PLWH who initiated ART after HIV diagnosis. ART initiation was treated as a time-dependent variable. Results
We enrolled 34581 PLWH with CD4 >500 cells/μL; 1838 (5.3%) initiated ART ≤30 days after diagnosis (immediate ART group), and 19 deaths were observed with a mortality rate of 1.04 per 100 person-years (PY). Fifty-eight deaths were documented among the 5640 PLWH in the delayed ART group with a mortality rate of 2.25 per 100 PY. There were 713 deaths among the 27103 PLWH in the no ART group with a mortality rate of 2.39 per 100 PY. After controlling for potential confounding factors, ART initiation at ≤30 days (adjusted HR, 0.37 [95% confidence interval, .23–.58]) was a statistically significant protective factor. Conclusions
We found that immediate ART is associated with a 63% reduction in overall mortality among PLWH with CD4 counts >500 cells/μL in China, supporting the recommendation to initiate ART immediately following HIV diagnosis.Reply to Kenyon
To the Editor—We thank Chris Kenyon for his comments [1] on our recent article [2], which showed that increased syphilis testing is associated with a relative increase in detection of asymptomatic early latent syphilis and a fall in secondary syphilis. Kenyon has hypothesized that the increase in proportion of early latent syphilis may be explained by an increasing proportion of repeated syphilis infections, which in turn are more likely to be asymptomatic [1]. However, we believe this is unlikely to explain our observations. In response, we undertook a further analysis of repeated syphilis infections among men who have sex with men (MSM) attending the Melbourne Sexual Health Centre (MSHC), where 32% of syphilis cases (1215 of 3831) in our study were diagnosed. Repeated syphilis infections were identified based on patient self-reported past history of syphilis using computer-assisted self-interview (CASI) at the MSHC from mid-2008 to ensure complete capture of diagnoses if patients had tested elsewhere outside the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance of Sexually Transmissible Infections and Blood-borne Viruses (ACCESS) network.
Increases in Asymptomatic Early Syphilis May Reflect Increases in Repeated Episodes of Syphilis and Not Enhanced Screening
To the Editor—In their analysis of men who have sex with men (MSM) attending a national sentinel network of 46 sexual health clinics in Australia between 2007 and 2014, Chow et al [1] found a decline in the proportion of syphilis cases that were secondary syphilis and a corresponding increase in early latent syphilis. These changes occurred during a period of increased coverage and frequency of syphilis testing in MSM. The authors interpret this association as representing an "interruption of syphilis progression" and thereby a reduction in the infectiousness of syphilis.
Increases in Neisseria gonorrhoeae With Reduced Susceptibility to Azithromycin Among Men Who Have Sex With Men in Seattle, King County, Washington, 2012–2016
Abstract
Background
Antimicrobial-resistant Neisseria gonorrhoeae is a major public health threat. The Centers for Disease Control and Prevention (CDC) recommends ceftriaxone 250 mg plus azithromycin (AZM) 1 g for gonorrhea treatment. Resistance to AZM could affect gonorrhea control efforts. Methods
Using gonococcal isolates collected at the Public Health–Seattle & King County (PHSKC) Sexually Transmitted Disease (STD) Clinic from 2012 to 2016, focusing on 2014–2016, we compared cases with the CDC AZM alert value minimum inhibitory concentration (MIC) (≥2 µg/mL) to those with AZM MIC ≤1 µg/mL, antimicrobial susceptibility profiles and clinical outcomes. Results
In 2012 and 2013, none of the 263 patients from whom we isolated N. gonorrhoeae from the urethra were infected with organisms with an AZM MIC ≥2 µg/mL. Between 2014 and 2016, 4.4% of 926 gonorrhea cases demonstrated reduced susceptibility to AZM; 93% of these cases occurred among men who have sex with men (MSM). Among MSM, 5.0% of 2014–2016 cases demonstrated reduced susceptibility to AZM. No AZM alert value isolates had concomitant cephalosporin resistance. There were 2 potential treatment failures: 1 pharyngeal infection treated with AZM 2 g alone, and 1 pharyngeal infection that persisted after study drug. Conclusions
Among MSM with gonorrhea in Seattle, 5% have gonorrhea with reduced susceptibility to AZM. The World Health Organization recommends changing treatment guidelines when >5% of isolates are resistant to a recommended drug. The emergence of resistant AZM gonorrhea should prompt reconsideration of current treatment recommendations, and highlights the need for new therapies for gonorrhea.Impact of Public Safety Policies on Human Immunodeficiency Virus Transmission Dynamics in Tijuana, Mexico
Abstract
Background
North Tijuana, Mexico is home to many individuals at high risk for transmitting and acquiring human immunodeficiency virus (HIV). Recently, policy shifts by local government impacted how these individuals were handled by authorities. Here we examined how this affected regional HIV transmission dynamics. Methods
HIV pol sequences and associated demographic information were collected from 8 research studies enrolling persons in Tijuana and were used to infer viral transmission patterns. To evaluate the impact of recent policy changes on HIV transmission dynamics, qualitative interviews were performed on a subset of recently infected individuals. Results
Between 2004 and 2016, 288 unique HIV pol sequences were obtained from individuals in Tijuana, including 46.4% from men who have sex with men, 42.1% from individuals reporting transactional sex, and 27.8% from persons who inject drugs (some individuals had >1 risk factor). Forty-two percent of sequences linked to at least 1 other sequence, forming 37 transmission clusters. Thirty-two individuals seroconverted during the observation period, including 8 between April and July 2016. Three of these individuals were putatively linked together. Qualitative interviews suggested changes in policing led individuals to shift locations of residence and injection drug use, leading to increased risk taking (eg, sharing needles). Conclusions
Near real-time molecular epidemiologic analyses identified a cluster of linked transmissions temporally associated with policy shifts. Interviews suggested these shifts may have led to increased risk taking among individuals at high risk for HIV acquisition. With all public policy shifts, downstream impacts need to be carefully considered, as even well-intentioned policies can have major public health consequences.Understanding the Promises and Hurdles of Metagenomic Next-Generation Sequencing as a Diagnostic Tool for Infectious Diseases
Abstract
Agnostic metagenomic next-generation sequencing (mNGS) has emerged as a promising single, universal pathogen detection method for infectious disease diagnostics. This methodology allows for identification and genomic characterization of bacteria, fungi, parasites, and viruses without the need for a priori knowledge of a specific pathogen directly from clinical specimens. Although there are increasing reports of mNGS successes, several hurdles need to be addressed, such as differentiation of colonization from infection, extraneous sources of nucleic acid, method standardization, and data storage, protection, analysis, and interpretation. As more commercial and clinical microbiology laboratories develop mNGS assays, it is important for treating practitioners to understand both the power and limitations of this method as a diagnostic tool for infectious diseases.HANDOC: A Handy Score to Determine the Need for Echocardiography in Non-β-Hemolytic Streptococcal Bacteremia
Abstract
Background
Non-β-hemolytic streptococci (NBHS) can cause infective endocarditis (IE). Echocardiography is used to diagnose IE, but it is not known which patients with NBHS bacteremia should undergo echocardiography. Method
Medical records of patients with NBHS bacteremia in southern Sweden from 2012 to 2014 were studied retrospectively. The patients were divided into 2 cohorts. In the first, correlations between the reported data and IE were studied. These variables were used to construct the HANDOC score, which was then validated in the second cohort. Results
Three hundred thirty-nine patients with NBHS bacteremia were included in the first cohort, of whom 26 fulfilled the criteria for IE. Several factors differed significantly between the patients with IE and those without. Among these variables, the presence of Heart murmur or valve disease; Aetiology with the groups of Streptococcus mutans, Streptococcus bovis, Streptococcus sanguinis, or Streptococcus anginosus; Number of positive blood cultures ≥2; Duration of symptoms of 7 days or more; Only 1 species growing in blood cultures; and Community-acquired infection were chosen to form the HANDOC score. With a cutoff between 2 and 3 points, HANDOC had a sensitivity of 100% and specificity of 73% in the first cohort. When tested in the validation cohort (n = 399), the sensitivity was 100% and the specificity 76%. Conclusions
HANDOC can be used in to identify patients with NBHS bacteremia who have a risk of IE so low that echocardiography can be omitted; therefore, its implementation might reduce the use of echocardiography.Familial Aggregation and Heritability of Loa loa Microfilaremia
Abstract
Background
For a given prevalence of Loa loa microfilaremia, the proportion of people with high densities varies significantly between communities. We hypothesized that this variation is related to the existence of familial clusters of hypermicrofilaremic individuals that would be the consequence of a genetic predisposition to present high L. loa microfilarial densities. Methods
A familial study was performed in 10 villages in the Okola Health District of Cameroon. Intrafamilial correlation coefficients and heritability estimates were assessed for both the presence of L. loa microfilaremia and individual microfilarial densities by controlling for age, sex, Mansonella perstans coinfection, and household effects. Results
Pedigrees were constructed for 1126 individuals. A significant familial susceptibility to be microfilaremic for L. loa was found for first-degree relatives (ρ = 0.08, P < .05; heritability = 0.23). Regarding individual microfilarial densities, a significant familial aggregation was demonstrated (ρ = 0.36 for first-degree and 0.27 for second-degree relatives). For first-degree relatives, the highest coefficient was found between mothers and daughters (ρ = 0.57). The overall heritability estimate for L. loa microfilarial density was 0.24 (P = .003). Conclusions
A significant genetic component governs L. loa microfilarial density. This supports the hypothesis that a genetic predisposition to be hypermicrofilaremic exists, leading to the presence of familial clusters of individuals at risk for postivermectin severe adverse events. This finding should be taken into account while developing sampling strategies (including a household-level sampling) to identify villages where community-directed treatment with ivermectin cannot be applied.Treatment of Chronic Q Fever: Clinical Efficacy and Toxicity of Antibiotic Regimens
Abstract
Background
Evidence on the effectiveness of first-line treatment for chronic Q fever, tetracyclines (TET) plus hydroxychloroquine (HCQ), and potential alternatives is scarce. Methods
We performed a retrospective, observational cohort study to assess efficacy of treatment with TET plus quinolones (QNL), TET plus QNL plus HCQ, QNL monotherapy, or TET monotherapy compared to TET plus HCQ in chronic Q fever patients. We used a time-dependent Cox proportional hazards model to assess our primary (all-cause mortality) and secondary outcomes (first disease-related event and therapy failure). Results
We assessed 322 chronic Q fever patients; 276 (86%) received antibiotics. Compared to TET plus HCQ (n = 254; 92%), treatment with TET plus QNL (n = 49; 17%), TET plus QNL plus HCQ (n = 29, 10%), QNL monotherapy (n = 93; 34%), or TET monotherapy (n = 54; 20%) were not associated with primary or secondary outcomes. QNL and TET monotherapies were frequently discontinued due to insufficient clinical response (n = 27, 29% and n = 32, 59%). TET plus HCQ, TET plus QNL, and TET plus QNL plus HCQ were most frequently discontinued due to side effects (n = 110, 43%; n = 13, 27%; and n = 12, 41%). Conclusions
Treatment of chronic Q fever with TET plus QNL appears to be a safe alternative for TET plus HCQ, for example, if TET plus HCQ cannot be tolerated due to side effects. Treatment with TET plus QNL plus HCQ was not superior to treatment with TET plus HCQ, although this may be caused by confounding by indication. Treatment with TET or QNL monotherapy should be avoided; switches due to subjective, insufficient clinical response were frequently observed.High Rates of Human Fecal Carriage of mcr-1–Positive Multidrug-Resistant Enterobacteriaceae Emerge in China in Association With Successful Plasmid Families
Abstract
Background
mcr-1–mediated colistin resistance in Enterobacteriaceae is concerning, as colistin is used in treating multidrug-resistant Enterobacteriaceae infections. We identified trends in human fecal mcr-1-positivity rates and colonization with mcr-1–positive, third-generation cephalosporin-resistant (3GC-R) Enterobacteriaceae in Guangzhou, China, and investigated the genetic contexts of mcr-1 in mcr-1–positive 3GC-R strains. Methods
Fecal samples were collected from in-/out-patients submitting specimens to 3 hospitals (2011–2016). mcr-1 carriage trends were assessed using iterative sequential regression. A subset of mcr-1–positive isolates was sequenced (whole-genome sequencing [WGS], Illumina), and genetic contexts (flanking regions, plasmids) of mcr-1 were characterized. Results
Of 8022 fecal samples collected, 497 (6.2%) were mcr-1 positive, and 182 (2.3%) harbored mcr-1–positive 3GC-R Enterobacteriaceae. We observed marked increases in mcr-1 (0% [April 2011] to 31% [March 2016]) and more recent (since January 2014; 0% [April 2011] to 15% [March 2016]) increases in human colonization with mcr-1–positive 3GC-R Enterobacteriaceae (P < .001). mcr-1–positive 3GC-R isolates were commonly multidrug resistant. WGS of mcr-1–positive 3GC-R isolates (70 Escherichia coli, 3 Klebsiella pneumoniae) demonstrated bacterial strain diversity; mcr-1 in association with common plasmid backbones (IncI, IncHI2/HI2A, IncX4) and sometimes in multiple plasmids; frequent mcr-1 chromosomal integration; and high mobility of the mcr-1–associated insertion sequence ISApl1. Sequence data were consistent with plasmid spread among animal/human reservoirs. Conclusions
The high prevalence of mcr-1 in multidrug-resistant E. coli colonizing humans is a clinical threat; diverse genetic mechanisms (strains/plasmids/insertion sequences) have contributed to the dissemination of mcr-1, and will facilitate its persistence.Orobanche cernua Loefling Attenuates Ultraviolet B-mediated Photoaging in Human Dermal Fibroblasts
Abstract
UV radiation is the primary cause of skin photoaging, which results in an increase in matrix metalloproteinases and degradation of collagen. Developing new natural antioxidant as photoprotective agents have become a popular area of research. Orobanche cernua Loefling is a parasitic plant that is rich in phenylethanoid glycosides (PhGs). This study investigated the photoprotective effects of the ethanolic extract of Orobanche cernua Loefling (OC) and its principal component acteoside on UVB-induced photoaging as well as their underlying molecular mechanisms in normal human dermal fibroblasts (NHDFs). Biological testing demonstrated that OC and acteoside possessed significant photoprotective activities, reducing MMP and IL-6 levels while improving type I procollagen synthesis in UVB-irradiated NHDFs. Further study showed that the protective mechanisms were the improvement of transcription factor Nrf2-mediated antioxidant defensive system, suppression of MAPK/AP-1 and activation of the TGF-β/Smad pathway. Together, our results suggested that OC might be a promising anti-photoaging agent against UV radiation induced skin damage.
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Publication date: Available online 25 July 2018 Source: Journal of Photochemistry and Photobiology B: Biology Author(s): Marco Ballestr...
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Editorial AJR Reviewers: Heartfelt Thanks From the Editors and Staff Thomas H. Berquist 1 Share + Affiliation: Citation: American Journal...
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https://www.youtube.com/watch?v=DFOhpBjLqN4&t=1s , Η ΘΕΡΑΠΕΙΑ ΓΙΑ ΟΛΕΣ ΤΙΣ ΑΣΘΕΝΕΙΕΣ 1 Περιεχόμενα Σύντομο βιογραφικό Πρόλογος μεταφραστ...
