Elimination and detoxification of 2,4-D by Umbelopsis isabellina with the involvement of cytochrome P450

Abstract

The chemical 2,4-dichlorophenoxyacetic acid (2,4-D) is used in agriculture as a herbicide. Its intensive use has an adverse effect on the environment. This study involved examining the degradation of 2,4-D compound by the filamentous fungus Umbelopsis isabellina. After 5 days of incubation, 98% of the herbicide (added at 25 mg L⁻¹) was found to be removed. The elimination of 2,4-D by U. isabellina was connected with the formation of 2,4-dichlorophenol (2,4-DCP), which resulted in a 60% decrease in the sample toxicity toward Artemia franciscana larvae. The metabolism of 2,4-D was inhibited by the addition of metyrapone, a known cytochrome P450 inhibitor. It provides evidence that cytochrome P450 system is involved in 2,4-D metabolism in U. isabellina.

Correction to: Economic growth and CO 2 emissions: an investigation with smooth transition autoregressive distributed lag models for the 1800–2014 period in the USA

Abstract

The original publication of this paper contains a mistake.

Novel topical agent containing superoxide dismutase 100 000 IU and 4% of plant extracts as a mono-therapy for atopic dermatitis

Abstract

Introduction

Corticosteroids are the mainstay of treatment for the acute phase of atopic dermatitis (AD), whereas topical emollients are mainly used for maintenance of remission. A topical agent that combines emollient and anti-inflammatory properties would achieve control of all phases of AD, without the need for chronic corticosteroid use.

Aim

To assess the efficacy of a novel topical agent containing superoxide dismutase (SOD) 100 000 IU and 4% of a combination of plant extracts (blackcurrant seed oil, sunflower oil concentrate, balloon vine extract).

Methods

Twenty patients (age range from 8 months to 72 years old) with mild-to-moderate atopic dermatitis were assessed. The product was used as mono-therapy, applied to the affected skin areas twice daily. Patients were evaluated before and after a 30-day course using the SCORAD and the Visual Analog Scale for assessment of pruritus intensity. Primary endpoint was improvement of AD according to SCORAD and clinical assessment. Secondary endpoint was patient satisfaction and improvement of pruritus.

Results

Mean SCORAD on day 0 was 32.61(range = 16.0-46.9) and decreased to 10.55 (range = 0-17.0) on day 30, reflecting a reduction of 67.6%. On day 30, all patients described significant improvement in pruritus and quality of sleep.

Conclusion

The application of the study product cream resulted in significant improvement of AD, as reflected by the objective SCORAD measurement, and the subjective assessment of pruritus and quality of life. This novel anti-inflammatory emollient product may emerge as a safe and effective therapeutic tool for all phases of AD without the adverse effects of chronic use of corticosteroids.

Markets with Some Limits

Analysis of the influence of collagen fibres in the dermis on skin optical reflectance by Monte Carlo simulation in a nine-layered skin model

Abstract

Background

Collagen fibres in the dermis play an important structural role in the skin. Age-related changes to these fibres cause wrinkles and slackness of facial skin. However, it is not clear how dermal collagen fibres affect skin colour. The purpose of this study was to clarify the influence of altered collagen fibres on skin colour, using both experimental measurement of fibre density and Monte Carlo simulations in an optical model of skin.

Methods

Reflection spectra were measured from the cheeks of 12 Japanese women (22-65 years old) by spectral colorimeter. Two-dimensional autocorrelation functions were calculated from second harmonics generation (SHG) images acquired from the same locations and used to calculate collagen density indices. Monte Carlo simulations of light reflectance by skin were performed using a nine-layered model that precisely imitates skin structure. The relationship between dermal collagen fibre density and skin reflection spectra was analysed.

Results

A positive correlation was found between collagen density and skin brightness, as measured by the colour value, L* (using the L*a*b* colour space). In addition, collagen density showed a strong inverse correlation with age and with the optical absorption of dermis. The Monte Carlo simulations showed that the reflection spectrum of skin changes when the scattering coefficient of the dermis is altered. These changes were the same for simulated and experimentally measured reflection spectra.

Conclusion

When collagen fibre density in the upper dermis is decreased with age, skin colour becomes less bright because light scattering in the skin is decreased.

A robust multi-objective bargaining methodology for inter-basin water resource allocation: a case study

Abstract

In this study, a new methodology is proposed to balance environmental and economic issues in water allocation under uncertainty. Two objective functions, including maximizing economic income (EI) and minimizing environmental pollution (EP), were considered as two groups of players to construct a deterministic multi-objective bargaining methodology (DMOBM). In the next step, it is enhanced to a robust multi-objective bargaining methodology (RMOBM), which is capable of incorporating the main uncertainties exist in the problem. A large-scale inter-basin water transfer case study was utilized to investigate the applicability of the developed model. The outputs of the models showed that Nash equilibrium provide a rather narrow range of solutions. According to the results, the required rounds to reach Nash equilibrium raised as the uncertainty level increased. In addition, higher levels of uncertainty lead to higher reduction in water allocating of receiving basin. Sensitivity analysis showed that economic income values are less sensitive to changes of uncertain parameters than the environmental objective function. The developed methodology could provide a framework to incorporate the behavior of different stakeholders. Furthermore, the proposed method can be reliable under the condition of facing water allocation uncertainties.

Enantioselective degradation of Myclobutanil and Famoxadone in grape

Abstract

The enantioselective degradation of myclobutanil and famoxadone enantiomers in grape under open field was investigated in this study. The absolute configuration of myclobutanil and famoxadone enantiomers was determined by the combination of experimental electronic circular dichroism (ECD) and calculated ECD spectra. The enantiomers residues of myclobutanil and famoxadone in grape were measured by sensitive high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS). The linearity, precision, accuracy, matrix effect, and stability were assessed. And the limit of quantification (LOQ) for each enantiomer of myclobutanil and famoxadone in grape was evaluated to be 1.5 and 2 μg kg⁻¹. The myclobutanil and famoxadone showed the enantioselective degradation in grape, and the enantioselectivity of degradation for myclobutanil was more pronounced than that for famoxadone. The half-lives were 13.1 days and 25.7 days for S-(+)-myclobutanil and R-(−)-myclobutanil in grape, separately. The half-life of S-(+)-famoxadone was 31.5 days slightly shorter than that of R-(−)-famoxadone with half-life being 38.5 days in grape. The probable reasons for the enantioselective degradation behavior of these two fungicides were also discussed. The results in the article might provide a reference to better assess the risks of myclobutanil and famoxadone enantiomers in grapes to human and environment.

Graphical abstract

The enantioselective analysis of myclobutanil and famoxadone in grape

Und sie bewegt sich doch!

Change over time in the rates of adverse events in patients receiving systemic therapy for psoriasis: a cohort study

Validity and Accuracy of a Mobile Phone Application for the Assessment of Wounds in Recessive Dystrophic Epidermolysis Bullosa

The role of T helper 25 (Th25) cells in the immune response to M. leprae

Rituximab as first line adjuvant in pemphigus: retrospective analysis of the long-term outcomes in a single center

All cause mortality in patients with basal and squamous cell carcinoma: A systematic review and meta-analysis

There are varying reports of the association of basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (SCC) with all-cause mortality.Patients with a history of SCC have an approximately 25% increased risk of all-cause mortality compared to the general population CC may be a clinical marker of a decline in health

Prognostic value of FDG-PET and DWI in breast cancer

Abstract

Objective

To investigate the prognostic value of preoperative FDG-PET/CT and diffusion weighted imaging (DWI) in patients with breast cancer.

Methods

A total of 73 patients with newly diagnosed invasive breast cancer who had undergone preoperative whole-body FDG-PET/CT and 3-Tesla breast MRI including DWI followed by surgery were identified. Effects of primary tumor PET parameters [maximum standardized uptake value (SUV_max), mean SUV (SUV_mean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] and DWI parameters [mean apparent diffusion coefficient (ADC_mean) and minimum ADC (ADC_min)] including clinicopathologic factors on disease-free survival (DFS) were retrospectively evaluated using the log-rank and Cox methods.

Results

After a median overall follow-up of 32.3 months in all patients, 6 (8.2%) of the 73 patients had recurrence. Receiver operating characteristic curve analysis and log-rank tests showed that patients with a high primary tumor SUV_max (≥ 3.60), MTV (≥ 3.15), and TLG (≥ 16.0) had a significantly lower DFS rate than those with a low SUV_max (< 3.60), MTV (< 3.15), and TLG (< 16.0), respectively (p = 0.0054, p = 0.0054, and p < 0.0001, respectively). SUV_mean, ADC_mean, and ADC_min were not significantly associated with recurrence. Univariate analysis showed that SUV_max (p = 0.0054), MTV (p = 0.0054), TLG (p < 0.0001), tumor size (p = 0.0083), estrogen receptor negativity (p = 0.046), progesterone receptor negativity (p = 0.0023), human epidermal growth factor receptor 2 positivity (p = 0.043), and the presence of axillary lymph node metastasis (p = 0.0037) were also significantly associated with recurrence. However, in multivariate analysis, none of them were an independent factor.

Conclusions

The preoperative SUV_max, MTV, and TLG of primary breast cancer are prognostic factors for recurrence, whereas ADC values are not.

Cyber Monday 2017

Corrigendum to "Familial primary localized cutaneous amyloidosis in a Japanese family" [J. Dermatol. Sci. 83 (2016) 162–164]

The authors regret:

Selected Literature Watch

Violence and Gender , Vol. 0, No. 0.

The removal of COD and NH 3 -N from atrazine production wastewater treatment using UV/O 3 : experimental investigation and kinetic modeling

Abstract

In this study, a UV/O₃ hybrid advanced oxidation system was used to remove chemical oxygen demand (COD), ammonia nitrogen (NH₃-N), and atrazine (ATZ) from ATZ production wastewater. The removal of COD and NH₃-N, under different UV and O₃ conditions, was found to follow pseudo-first-order kinetics with rate constants ranging from 0.0001–0.0048 and 0.0015–0.0056 min⁻¹, respectively. The removal efficiency of ATZ was over 95% after 180 min treatment, regardless the level of UV power. A kinetic model was further proposed to simulate the removal processes and to quantify the individual roles and contributions of photolysis, direct O₃ oxidation, and hydroxyl radical (OH·) induced oxidation. The experimental and kinetic modeling results agreed reasonably well with deviations of 12.2 and 13.1% for the removal of COD and NH₃-N, respectively. Photolysis contributed appreciably to the degradation of ATZ, while OH· played a dominant role for the removal of both COD and NH₃-N, especially in alkaline environments. This study provides insights into the treatment of ATZ containing wastewater using UV/O₃ and broadens the knowledge of kinetics of ozone-based advanced oxidation processes.

Potassium bromate as a food additive: a case study of Tunisian breads

Abstract

This study is the first investigation of potassium bromate as a food additive in Tunisian breads. In this study, levels of residual bromate were determined in 91 commercial breads from 31 bakeries randomly selected in two Tunisian cities. In total, 13 different types of bread were analyzed using a spectrophotometric method of bromate analysis. Bromate concentrations ranged from 5.95 to 49.31 μg g⁻¹, with an overall mean concentration of 19.92 μg g⁻¹. Significant differences were noticed between bromate levels in breads from bakeries of the two cities (P < 0.01). Based on the types of breads, Muffin contained the highest mean concentration of bromate residue (29.92 μg g⁻¹) as opposed to bread without salt, which had the lowest mean bromate level (13.53 μg g⁻¹). Compared to data available from other countries, our results showed relatively high bromate levels, which could potentially lead to long term toxic and carcinogenic effects in the Tunisian population.

A review of heavy metal pollution levels and health risk assessment of urban soils in Chinese cities

Abstract

This study assessed literature-based data for the period 2006–2016 regarding heavy metal (As, Cd, Cr, Cu, Pb, Ni, Zn, and Hg) concentrations in soils from 32 Chinese cities and the associated human health risks. The mean concentrations of the eight metals were lower than the soil environmental quality standards in China, but were much higher than the background values for most cities. The enrichment factor (EF) and geoaccumulation index (I _geo) values showed moderate pollution levels, possibly influenced by anthropogenic activity for Cd, Hg, Pb, and Zn. The pollution levels in eastern cities were much higher than those in western cities, and heavy metals concentrations in different types of cities followed the order: industrial based cities > more developed cities > metropoles > underdeveloped cities. The human health risk assessment for heavy metals in most cities indicated that non-carcinogenic risks were within threshold values (HI < 1). The total carcinogenic risk due to As, Cr, and Ni in most urban areas was in excess of 1 × 10⁻⁵, but was lower than 1 × 10⁻⁴. However, in some cities (e.g., Baoji City, Tiyuan City, and Xuzhou City), Ni and Cr have potential cancer risks for both adults and children. Compared to adults, children could be more seriously threatened by heavy metal contamination in soils. In general, we recommend that Cd, Hg, and Pb are selected as priority heavy metals pollutants that require control in Chinese cities.

Transcriptional changes measured in rice roots after exposure to arsenite-contaminated sediments

Abstract

Transcriptional analyses are discussed to provide a deeper understanding of the molecular mechanisms underlying toxic effects. Thus, they can complement classic ecotoxicological test methods and potentially allow the identification of biomarkers associated to the exposure of chemical stressors and or adverse biological effects. This feasibility study intended to identify a set of potential gene expression biomarkers for arsenite-exposure in rice roots that could complement the informative value of an existing sediment-contact test with rice. A sediment-contact test with Oryza sativa with the parameters inhibition of root and shoot elongation as phenotypic endpoints was used as basis. Rice plants were exposed to arsenite-spiked sediments. Transcriptomic changes in response to arsenite were observed by means of cDNA-microarray analysis regarding the whole-transcriptome at two sublethal arsenite concentrations. In order to identify candidate biomarker genes, differentially expressed genes were identified. Arsenite-induced differentially expressed genes were significantly associated with gene ontology (GO)-terms that indicated a general stress response. Of the differentially expressed genes, five genes were selected and their expression was measured at seven arsenite concentrations by means of qPCR in order to obtain their expression profiles. Three candidate biomarker genes showed a dose-dependent upregulation, while two showed no clear dose-dependent expression. The expression of all candidate biomarkers was also assessed in rice plants grown on two arsenic-contaminated natural sediments, but only one biomarker gene showed the expected upregulation.

Mucociliary transport, differential white blood cells, and cyto-genotoxicity in peripheral erythrocytes in fish from a polluted urban pond

Abstract

The present study evaluated the water quality of a polluted pond through the analysis of in vitro mucociliary transport, hematological parameters, and biomarkers of cyto-genotoxicity in the Nile tilapia (Oreochromis niloticus). Blood and mucus samples were collected from ten specimens from the polluted pond and from ten specimens from a control area. The fish were anesthetized with 3% benzocaine, mucus was collected directly from the gills, and blood was drawn from the caudal artery. Blood smears were stained using the May-Grünwald Giemsa process for the differential leukocyte counts and to determine the frequency of leukocytes, thrombocytes, erythroblasts, micronuclei, and nuclear abnormalities. The results revealed low transportability in vitro, a high percentage of monocytes and eosinophils, and increased frequency of leukocytes and nuclear abnormalities in fish from the polluted pond. However, the frequency of thrombocytes and erythroblasts and the percentage of lymphocytes and neutrophils were significantly lower. It is possible to conclude that changes in fish are due to poor water quality and that these non-destructive biomarkers can be used for the biomonitoring of aquatic environments vulnerable to contamination.

Toxicities and risk assessment of heavy metals of the six most consumed fish from the Marmara Sea

Abstract

Bream, anchovy, horse mackerel, sea bass, sardine, and whiting that are commonly consumed by the Turkish community were collected from the Marmara Sea in September and March and were analyzed for trace elements and for fat content. The total concentrations of some metals in these fish were determined using ICP-MS in acid extracts obtained after microwave digestion. The seasonal fat contents of the fish samples were determined gravimetrically following a Soxhlet extraction method. Experimental results were evaluated statistically using t tests and principal component analyses. This enabled the comparison of the elements' contents in the fish samples in March and September and also led to an investigation into whether or not there is a relationship between the elements' contents and the fat amount. The results of this work showed that a significant temporal difference was observed. This difference was not related to the seasonal variation in fat concentrations.

Health risk assessment of arsenic and heavy metals (Cd, Cu, Co, Pb, and Sn) through consumption of caviar of Acipenser persicus from Southern Caspian Sea

Abstract

In the current study contents of As, Cd, Cu, Co, Pb, and Sn were determined in the caviar of Persian sturgeon collected from Southern Caspian Sea sampling site. After acid digestion of caviar specimens, the concentrations of elements determined using ICP-OES. The results showed that the mean concentrations (mg kg⁻¹) of elements in caviar samples were 0.01 for As, 0.05 for Cd, 1.42 for Cu, 0.01 for Co, 0.01 for Pb, and 0.28 for Sn and for all the elements are significantly lower than the adverse level for the human consumption. Also, health risk index (HRI) values were within the safe limits (HRI < 1). Therefore, there is no potential health risk to adults and children via consumption of caviar. Due to the discharge of hazardous chemicals into the marine ecosystems especially the Caspian Sea, residue analysis of pollutants in the sea foods is recommended.

Capacity of six shrub species to retain atmospheric particulates with different diameters

Abstract

Garden plants can absorb and retain atmospheric particles and are important for remediating environmental pollution. In this study, the dust retention characteristics of six typical shrub species were measured in the greenbelt of a road in the Chengyang District of Qingdao, China, and the maximum capacity for dust retention of each species was determined. The different diameters and areas occupied by particulate matter (PM) were analyzed on the leaf surfaces of the plants. Based on the results for the six shrub species, the rank order of average content of dust retention per unit leaf area was Euonymus japonicus > Pyracantha fortuneana > Ligustrum vicaryi > Amygdalus triloba > Ligustrum sinense > Forsythia suspensa, whereas the rank order of average content per unit volume was E. japonicus > A. triloba > P. fortuneana > L. vicaryi > L. sinense > F. suspensa. The maximum content of dust retention per unit leaf area was reached in approximately 24 days. Plants retained atmospheric PM primarily on the upper leaf surfaces. The primary portion of particles on the leaves was PM₁₀ (over 80%), and PM_2.5 was the principal component of PM₁₀. Leaf surface structure significantly affected the abilities of plants to retain PM, and the plants with a thick wax layer or large and dense stomata adsorbed more PM, such as E. japonicus. This study provides a scientific basis for the capacity of landscape plants to retain different diameter particulates.

Effect of water constituents on the degradation of sulfaclozine in the three systems: UV/TiO 2 , UV/K 2 S 2 O 8 , and UV/TiO 2 /K 2 S 2 O 8

Abstract

Bicarbonate, phosphate, chloride ions, and humic substances are among the constituents most widely present in natural waters. These non-target constituents can greatly affect the efficiency of advanced oxidation processes used for water decontamination due to their capacity to interfere with the adsorption of the target compounds on the surface of TiO₂, absorb photons, scavenge hydroxyl radicals (·OH), and generate photochemical reactive intermediates. In this work, the effect of these constituents on the degradation of sulfaclozine (SCL) was monitored in three different AOPs systems: UV/TiO₂, UV/K₂S₂O₈, and UV/TiO₂/K₂S₂O₈. It was shown that bicarbonate (HCO₃⁻) and phosphate (HPO₄²⁻) ions enhanced the degradation of SCL in UV/TiO₂ and UV/TiO₂/K₂S₂O₈ systems whereas the addition of humic substances influenced these rates with a much smaller extent. On the other hand, the degradation rate of SCL in the UV/K₂S₂O₈ system was not affected by the presence of HCO₃⁻ and HPO₄²⁻ but was inhibited in the presence of humic substances. In addition, the different mechanisms that can take place in the presence of these constituents were discussed and the degradation rate enhancement in presence of HCO₃⁻ and HPO₄²⁻ was attributed to the formation of new reactive species such as carbonate (CO₃^·–) and hydroxyl (·OH) radicals activated by TiO₂ holes (h⁺). In the presence of chloride (Cl⁻) and nitrate (NO₃⁻) ions, an enhancement of SCL adsorption on the surface of TiO₂ was observed. Finally, a comparative study of the degradation of SCL in river water and ultrapure water was reported.

Rhumatisme psoriasique en France, du nourrisson à la personne âgée : données de deux études transversales multicentriques

Publication date: Available online 13 November 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): A. Galezowski, F. Maccari, S. Hadj-Rabia, M.-L. Sigal, A. Phan, M. Lahfa, A.-C. Bursztejn, H. Barthélémy, F. Boralévi, Z. Reguiai, C. Chiavérini, E. Estève, E. Bourrat, M. Ruer-Mulard, A. Beauchet, E. Mahé
IntroductionLe rhumatisme psoriasique touche 20 à 30 % des patients atteints de psoriasis cutané. Peu de données épidémiologiques sont disponibles en France sur sa prévalence, ses associations avec l'atteinte dermatologique et ses comorbidités.ObjectifsÉvaluer les aspects épidémiologiques et associations cliniques et épidémiologiques du rhumatisme psoriasique chez les enfants et les adultes, en France.MéthodesDeux études transversales, multicentriques ont été menées en France chez les enfants (χ-Psocar, 23 centres de dermatologie pédiatrique membres du GR SFDP, 1 an) et les adultes (Resopsocar, 29 centres de dermatologie membres du GEM RESOPSO, 4 mois) pour étudier les comorbidités cardiovasculaires et métaboliques du psoriasis.RésultatsParmi les 313 enfants (garçons : 47,6 % ; âge moyen, 9,4 ans) et 1954 adultes (hommes : 56,0 % ; âge moyen : 48,5 ans) atteints de psoriasis, 4,2 % des enfants et 21,0 % des adultes souffraient de rhumatisme psoriasique. La prévalence augmentait avec l'âge : 2,2 % des enfants, 14,2 % des adolescents et plus de 20 % après 40 ans. Elle diminuait après 70 ans (19,4 %). Quel que soit l'âge, le sexe n'était pas associé au rhumatisme psoriasique. Chez les enfants, le rhumatisme était associé à l'atteinte unguéale (p=0,04) et à la sévérité de la maladie (p=0,0004). Chez les adultes il était associé au psoriasis en plaques (p=0,002), à la sévérité de la maladie (p<0,0001) et à l'obésité (p<0,0001). Le psoriasis en plaques localisé (cuir chevelu, psoriasis palmo-plantaire par exemple) était moins souvent associé au rhumatisme psoriasique (p<0,05).ConclusionsCes deux études transversales menées en France sur 2267 patients, principalement hospitaliers, donnent une idée de la prévalence du rhumatisme psoriasique tout au long de la vie. La prévalence augmente progressivement avec l'âge, sans différence de genre, avant de diminuer chez les personnes âgées. Nous confirmons l'association avec l'onychopathie psoriasique dès l'enfance et avec l'obésité chez les adultes.BackgroundPsoriatic arthritis affects 20–30% of patients with psoriasis. Few epidemiological data are available in France about its prevalence and its association with skin lesions and comorbidities.ObjectivesTo assess the epidemiological aspects and the risk factors for psoriatic arthritis in children and adults in France.MethodsTwo cross-sectional studies were conducted in France in children (χ-Psocar, 23 pediatric dermatology centers belonging to the SFDP, 1 year) and adults (Resopsocar, 29 dermatology centers belonging to GEM RESOPSO, 4 months) to study the link between psoriasis and cardiovascular and metabolic comorbidities.ResultsThree hundred and thirteen children (males: 47.6%; mean age: 9.4 yrs) and 1,954 adults (males: 56.0%; mean age: 48.5 yrs) with psoriasis were included, with 4.2% of the children and 21.0% of the adults presenting psoriatic arthritis. Prevalence increased with age: 2.2% of children, 14.2% of adolescents, and over 20% after 40 years. It decreased after the age of 70 years (19.4%). Regardless of age, arthritis was not associated with gender. In the children's group, rheumatism was associated with nail involvement (P=0.04) and disease severity (P=0.0004). Adult rheumatism was associated with generalized plaque psoriasis (P=0.002), disease severity (P<0.0001), and obesity (P<0.0001). Localized plaque psoriasis was less often associated with arthritis (P<0.05).ConclusionsThese two cross-sectional studies conducted in 2267 patients in France yielded information on the prevalence of joint involvement from infants to elderly subjects. It is the first study conducted in a single population to provide data for the whole population. Prevalence gradually increases with age, without gender difference, before decreasing in old age. We confirm the association of nail involvement in the first years of life, and of obesity in adults.

Melanoma tumors exhibit a variable but distinct metabolic signature

Reinterpreting the Right to an Open Future: From Autonomy to Authenticity

Abstract

This paper reinterprets a child's right to an open future as justified by authenticity rather than autonomy. It argues that authenticity can be recognized as valuable by people whose conceptions of the good do not value autonomy. As a running example, the paper considers ultra-Orthodox Jews who lead separatist lives and who deny their sons secular education beyond an elementary school level. If their adult sons want to have careers and participate in life outside the religious enclave, they cannot easily do so. The parents see no reason to protect their child's autonomy (which they do not value) or to prepare their child for a life that conflicts with their values. This paper provides one response to their concerns. Following a political-liberal project of seeking overlapping consensus, it tries to base demands that children be prepared for varied futures on values that reasonable religious people can embrace.

Molecular photoprotection of human keratinocytes in vitro by the naturally occurring mycosporine-like amino acid (MAA) palythine

Summary

Background

Solar ultraviolet radiation (UVR) induces molecular and genetic changes in the skin, which result in skin cancer, photoageing and photosensitivity disorders. The use of sunscreens is advocated to prevent such photodamage, however most formulations contain synthetic UVR filters that are non-biodegradable and can damage fragile marine ecosystems. Mycosporine-like amino acids (MAA) are natural UVR-absorbing compounds that have evolved in marine species for protection against chronic UVR exposure in shallow-water habitats.

Objectives

To determine if palythine, a photostable model MAA, could offer protection against a range of UVR-induced damage biomarkers that are important in skin cancer and photoageing.

Methods

HaCaT human keratinocytes were used to assess the photoprotective potential of palythine using a number of endpoints including cell viability, DNA damage (non-specific, cyclobutane pyrimidine dimers and oxidatively generated damage), gene expression changes (linked to inflammation, photoageing and oxidative stress) and oxidative stress. The anti-oxidant mechanism was investigated using chemical quenching and Nrf2 pathway activation assays.

Results

Palythine offered statistically significant protection (p<0.005) against all endpoints tested even at extremely low concentrations (0.3% w/v). Additionally, palythine was found to be a potent antioxidant, reducing oxidatively generated stress, even when added post exposure.

Conclusions

Palythine is an extremely effective multifunctional photoprotective molecule in vitro that has potential to be developed as a natural and biocompatible alternative to synthetic UVR filters.

This article is protected by copyright. All rights reserved.

Naevus lightening in melanoma patients under BRAF/MEK inhibitor combination therapy versus checkpoint immunotherapy: a histologic and immunohistochemistry analysis

Abstract

The advent of targeted therapies using BRAF or MEK inhibitors (BRAFi or MEKi) or their combinations (BiMiC) as well as checkpoint immunotherapies based on antibodies to CTLA4 or PD1 has recently brought about a drastic revolution in the treatment of advanced cancers, in particular of melanoma. These therapies are, however, not without side effects. Many of them involve the skin and range from keratosis to squamous cell carcinomas under BRAFi monotherapy and from lichenoid reactions to vitiligo under immunotherapies.

This article is protected by copyright. All rights reserved.

Real-time wireless tumor tracking during breast conserving surgery

Abstract

Purpose

To evaluate a novel surgical navigation system for breast conserving surgery (BCS), based on real-time tumor tracking using the Calypso \(\circledR \) 4D Localization System (Varian Medical Systems Inc., USA). Navigation-guided breast conserving surgery (Nav-BCS) was compared to conventional iodine seed-guided BCS ( \(^{125}\) I-BCS).

Methods

Two breast phantom types were produced, containing spherical and complex tumors in which wireless transponders (Nav-BCS) or a iodine seed ( \(^{125}\) I-BCS) were implanted. For navigation, orthogonal views and 3D volume renders of a CT of the phantom were shown, including a tumor segmentation and a predetermined resection margin. In the same views, a surgical pointer was tracked and visualized. \(^{125}\) I-BCS was performed according to standard protocol. Five surgical breast oncologists first performed a practice session with Nav-BCS, followed by two Nav-BCS and \(^{125}\) I-BCS sessions on spherical and complex tumors. Postoperative CT images of all resection specimens were registered to the preoperative CT. Main outcome measures were the minimum resection margin (in mm) and the excision times.

Results

The rate of incomplete tumor resections was 6.7% for Nav-BCS and 20% for \(^{125}\) I-BCS. The minimum resection margins on the spherical tumors were 3.0 ± 1.4 mm for Nav-BCS and 2.5 ± 1.6 mm for \(^{125}\) I-BCS (p = 0.63). For the complex tumors, these were 2.2 ± 1.1 mm (Nav-BCS) and 0.9 ± 2.4 mm ( \(^{125}\) I-BCS) (p = 0.32). Mean excision times on spherical and complex tumors were 9.5 ±  2.7 min and 9.4 ± 2.6 min (Nav-BCS), compared to 5.8 ± 2.2  min and 4.7 ± 3.4 min ( \(^{125}\) I-BCS, both (p < 0.05).

Conclusions

The presented surgical navigation system improved the intra-operative awareness about tumor position and orientation, with the potential to improve surgical outcomes for non-palpable breast tumors. Results are positive, and participating surgeons were enthusiastic, but extended surgical experience on real breast tissue is required.

Growth Trajectories, Breast Size, and Breast-Tissue Composition in a British Pre-Birth Cohort of Young Women

Abstract

Mammographic % density, the proportion of fibroglandular tissue in the breast, is a strong risk factor for breast cancer, but its determinants in young women are unknown. We examined associations between magnetic resonance imaging (MRI) breast-tissue composition at age 21 years and prospectively-collected measures of body size and composition from birth to early adulthood, and markers of puberty (all standardized), in a sample of 500 nulliparous women from a pre-birth cohort of children born in Avon, England, in 1991–1992 and followed up to 2011–2014. Linear models were fitted to estimate relative change in MRI % water, which is equivalent to mammographic % density, associated with one standard deviation increase in the exposure of interest. In mutually-adjusted analyses, MRI % water was positively associated with birth weight (relative change = 1.03 (95% confidence interval: 1.00, 1.06)) and pubertal height growth (1.07 (1.02, 1.13)), but inversely associated with pubertal weight growth (0.86 (0.84, 0.89)) and changes in dual-energy x-ray absorptiometry % body fat mass (e.g., 0.96 (0.93, 0.99)), for change between ages 11–13.5 years). Ages at thelarche and menarche were positively associated with MRI % water, but these associations did not persist upon adjustment for height and weight growth. These findings support the hypothesis that growth trajectories influence breast-tissue composition in young women, whereas puberty plays no independent role.

Decomposition of the Total Effect in the Presence of Multiple Mediators and Interactions

Abstract

Mediation analysis allows decomposing a total effect into a direct effect of the exposure on the outcome and an indirect effect operating through a number of possible hypothesized pathways. Recent studies have provided formal definitions of direct and indirect effects when multiple mediators are of interest, and have described parametric and semi-parametric methods for their estimation. Investigating direct and indirect effects with multiple mediators, however, can be challenging in the presence of multiple exposure-mediator and mediator-mediator interactions. In this paper we derive a decomposition of the total effect that unifies mediation and interaction when multiple mediators are present. We illustrate the properties of the proposed framework, in a secondary analysis of a pragmatic trial for the treatment of schizophrenia. The decomposition is employed to investigate the interplay of side-effects and psychiatric symptoms in explaining the effect of antipsychotic on quality of life in schizophrenia patients. Our result offers a valuable tool to identify the proportions of total effect due to mediation and interaction when more than one mediator is present, providing the finest decomposition of the total effect that unifies multiple mediators and interactions.

Targeted Treatment of Yaws With Household Contact Tracing: How Much do we Miss?

Abstract

Yaws is a disabling bacterial infection primarily found in warm and humid tropical areas. The World Health Organisation strategy mandates an initial round of total community treatment (TCT) with single-dose azithromycin followed either by further TCT or active case finding and treatment of cases and their contacts (the Morges strategy). We wish to investigate the effectiveness of the Morges strategy. We employ a stochastic household model to study the transmission of infection using data collected from a pre-TCT survey conducted in the Solomon Islands. We use this model to assess the proportion of asymptomatic infections that occur in households without active cases. This analysis indicates that targeted treatment of cases and their household contacts would miss a large fraction of asymptomatic infections (between 65% and 100%). This fraction actually increases at lower prevalences. Even assuming that all active cases and their households are successfully treated, our analysis demonstrates that at all prevalences present in the dataset, up to 90% of (active and asymptomatic) infections would not be treated under household-based contact tracing. Mapping was undertaken as part of the study "Epidemiology of Yaws in the Solomon Islands and the Impact of a Trachoma Control Programme", September-October 2013.

Sudden Unexpected Cardiac Death on Monday in Younger and Older Men: The Manitoba Follow-up Study

Extragenitale, disseminierte Infektion mit humanen Papillomaviren

Zusammenfassung

Bei einem 50-jährigen Patienten mit seit 5 Jahren bestehender großflächiger Warzenmanifestation und extremem Pruritus kamen wir zur Diagnose einer reaktivierten HPV (humane Papillomaviren)-Infektion durch 3 molekulargenetisch gesicherte Virustypen (6, 16, 18), die im Impfstoff Gardasil® enthalten sind. Nachdem konventionelle Therapieverfahren keinen Erfolg erbrachten, zeigte sich nach Gardasil®-Immunisierung rasch ein signifikanter Rückgang der Hautmanifestation. Inwieweit therapieresistente HPV-Infektionen mittels einer aktiven HPV-Impfung zu beeinflussen sind, sollte in weiteren Studien untersucht werden.

Endothelial TNF-α induction by Hsp60 secreted from THP-1 monocytes exposed to hyperglycaemic conditions

Abstract

A non-resolving inflammation of the endothelium is recognised to be an important process leading to atherosclerosis. In diabetes, this process is thought to account for a significant number of cardiovascular disease-associated death and disability. However, the molecular mechanisms by which diabetes contributes to endothelial inflammation remain to be established. Whilst there is some evidence linking hyperglycaemia-induced reactive oxygen species (ROS) formation by the mitochondrial electron-transport chain to oxidative stress, cellular injury and apoptosis in the endothelium, a clear link to endothelium inflammation has not yet been established. The mitochondrial molecular stress protein Hsp60 is known to be secreted from mammalian cells and is capable of activating pro-inflammatory mediators on target cells expressing Toll-like receptors (TLRs). Hsp60 is also known to be elevated in serum of diabetes patients and has been shown to be upregulated by hyperglycaemic growth conditions in cultured human HeLa cells. This study shows that Hsp60 induced in human acute monocyte leukaemia cell line (THP-1) cells grown under hyperglycaemic conditions (25 mM glucose) was able to be secreted into growth media. Furthermore, the secretion of Hsp60 from THP-1 cells was able to be inhibited by 5,5-(N-N-dimethyl)-amiloride hydrochloride (DMA), an exosomal inhibitor. Interestingly, the conditioned media obtained from THP-1 cells grown in the presence of 25 mM glucose was able to induce the secretion of TNF-α in human vascular endothelium cell line (HUVEC). When conditioned media was immuno-depleted of Hsp60, there was a significant reduction in the release of TNF-α from the HUVEC cells. This suggests that a potential link may exist between hyperglycaemia-induced expression of Hsp60 in monocyte cells and vascular inflammation. Circulating levels of Hsp60 due to mitochondrial stress in diabetes patients could therefore be an important modulator of inflammation in endothelial cells and thus contribute to the increased incidences of atherosclerosis in diabetes mellitus.

Diabetes und Krebs – den Zusammenhängen auf der Spur

ÖWAW Kalender

February 1 2018 News

Factors associated with 30-day mortality in respiratory infections caused by Streptococcus pneumoniae

Abstract

We evaluated the relationship between initial antibiotic therapy and clinical outcomes in 5005 patients with microbiologically confirmed infections due to Streptococcus pneumoniae. In multivariable analysis, the receipt of "discordant" empiric antibiotic therapy was not associated with 30-day mortality (Hazard Ratio 0.94, 95% CI 0.67–1.32).

The European Society for Medical Oncology (ESMO) Precision Medicine Glossary

Abstract

Background

Precision medicine is rapidly evolving within the field of oncology and has brought many new concepts and terminologies that are often poorly defined when first introduced, which may subsequently lead to miscommunication within the oncology community. The European Society for Medical Oncology (ESMO) recognises these challenges and is committed to support the adoption of precision medicine in oncology. To add clarity to the language used by oncologists and basic scientists within the context of precision medicine, the ESMO Translational Research and Personalised Medicine Working Group has developed a standardised glossary of relevant terms.

Materials and methods

Relevant terms for inclusion in the glossary were identified via an ESMO member survey conducted in Autumn 2016, and by the ESMO Translational Research and Personalised Medicine Working Group members. Each term was defined by experts in the field, discussed and, if necessary, modified by the Working Group before reaching consensus approval. A literature search was carried out to determine which of the terms, 'precision medicine' and 'personalised medicine', is most appropriate to describe this field.

Results

A total of 43 terms are included in the glossary, grouped into five main themes—(i) mechanisms of decision, (ii) characteristics of molecular alterations, (iii) tumour characteristics, (iv) clinical trials and statistics and (v) new research tools. The glossary classes 'precision medicine' or 'personalised medicine' as technically interchangeable but the term 'precision medicine' is favoured as it more accurately reflects the highly precise nature of new technologies that permit base pair resolution dissection of cancer genomes and is less likely to be misinterpreted.

Conclusions

The ESMO Precision Medicine Glossary provides a resource to facilitate consistent communication in this field by clarifying and raising awareness of the language employed in cancer research and oncology practice. The glossary will be a dynamic entity, undergoing expansion and refinement over the coming years.

Pruritic and Painful Red Nodules and Papules

(See page 1953 for the Answer to the Photo Quiz.)

In the Literature

News

Pruritic and Painful Red Nodules and Papules

(See page 1952 for the Photo Quiz.)

Cover

Erratum

An error appeared in the 1 March 2017 issue of the journal [Tamma PD, Avdic E, Keenan JF, et al. What Is the More Effective Antibiotic Stewardship Intervention: Preprescription Authorization or Postprescription Review With Feedback? Clin Infect Dis 2017; 64:537–43]. In Figure 3, the decrease in antibiotic use when these firms received PPRF after the washout period should be shown as a solid line to the right of vertical line; slope of −2.45 DOT per 1000 PD, P = .02; not a dotted line.

Influenza Among Young Children in Bangladesh: Clinical Characteristics and Outcomes From a Randomized Clinical Trial

Abstract

Background

Influenza causes substantial morbidity in children worldwide, although influenza vaccine is seldom used in low-resource settings. More information on the clinical presentation of influenza and the efficacy of vaccine is needed to inform policy.

Methods

In 2013 we conducted a randomized, placebo-controlled clinical trial of live attenuated influenza vaccine (LAIV) in children aged 24–59 months in Bangladesh (N = 1761). If participants met prespecified specimen collection criteria, we collected nasopharyngeal washes for testing by singleplex reverse-transcription polymerase chain reaction (RT-PCR) for laboratory-confirmed influenza virus infection (LCI). A panel of RT-PCR assays was used to detect noninfluenza respiratory viruses. Primary efficacy results have been reported. In this analysis of prespecified and post hoc objectives from the trial, we compared signs and symptoms between LCI and non-LCI cases and estimated the efficacy of LAIV against moderate-to-severe LCI and other prespecified non-LCI clinical outcomes including all-cause pneumonia and acute otitis media.

Results

The most common signs and symptoms of LCI were fever, cough, and runny nose. The combination of subjective fever and cough had a 63% sensitivity for LCI. The combination of measured fever, cough, and runny nose was most specific (90%) but had low sensitivity (32%) for LCI. The efficacy of LAIV against vaccine-strain moderate-to-severe LCI was 56.7% (95% confidence interval, 9.5%–79.2%). No statistically significant vaccine efficacy was found against the non-laboratory-confirmed clinical outcomes.

Conclusions

It was not possible to distinguish LCI from noninfluenza viral infections on clinical evaluations alone in this population of Bangladeshi children. LAIV was efficacious against moderate-to-severe LCI.

Clinical Trials Registration

NCT01797029.

Antibody Kinetics and Response to Routine Vaccinations in Infants Born to Women Who Received an Investigational Trivalent Group B Streptococcus Polysaccharide CRM 197 -Conjugate Vaccine During Pregnancy

Abstract

Background

Maternal vaccination against group B Streptococcus (GBS) might provide protection against invasive GBS disease in infants. We investigated the kinetics of transplacentally transferred GBS serotype-specific capsular antibodies in the infants and their immune response to diphtheria toxoid and pneumococcal vaccination.

Methods

This phase 1b/2, observer-blind, single-center study (NCT01193920) enrolled infants born to women previously randomized (1:1:1:1) to receive either GBS vaccine at dosages of 0.5, 2.5, or 5.0 μg of each of 3 CRM₁₉₇-glycoconjugates (serotypes Ia, Ib, and III), or placebo. Infants received routine immunization: combination diphtheria vaccine (diphtheria-tetanus-acellular pertussis–inactivated poliovirus/Haemophilus influenzae type b vaccine; age 6/10/ 14 weeks) and 13-valent pneumococcal CRM₁₉₇-conjugate vaccine (PCV13; age 6/14 weeks and 9 months). Antibody levels were assessed at birth, day (D) 43, and D91 for GBS serotypes; 1 month postdose 3 (D127) for diphtheria; and 1 month postprimary (D127) and postbooster (D301) doses for pneumococcal serotypes.

Results

Of 317 infants enrolled, 295 completed the study. In infants of GBS vaccine recipients, GBS serotype-specific antibody geometric mean concentrations were significantly higher than in the placebo group at all timepoints and predictably decreased to 41%–61% and 26%–76% of birth levels by D43 and D91, respectively. Across all groups, ≥95% of infants were seroprotected against diphtheria at D127 and ≥91% of infants had seroprotective antibody levels against each PCV13 pneumococcal serotype at D301.

Conclusions

Maternal vaccination with an investigational CRM₁₉₇-glycoconjugate GBS vaccine elicited higher GBS serotype-specific antibody levels in infants until 90 days of age, compared with a placebo group, and did not affect infant immune responses to diphtheria toxoid and pneumococcal vaccination.

Clinical Trials Registration

NCT01193920.

Effectiveness of Measles Vaccination and Immune Globulin Post-Exposure Prophylaxis in an Outbreak Setting—New York City, 2013

Abstract

Background

Measles, mumps, and rubella vaccine (MMR) or immune globulin (IG) are routinely used for measles post-exposure prophylaxis (PEP). However, current literature on the effectiveness of measles PEP is limited and variable. Here, we examined the effectiveness of MMR and IG PEP among children exposed to measles during an outbreak in New York City (NYC) in 2013.

Methods

Contacts were identified by the NYC Department of Health and Mental Hygiene between 13 March 2013 and 30 June 2013. Immunity to measles and receipt of PEP was determined for contacts. PEP effectiveness [(1 − relative risk of developing measles) × 100] was calculated for MMR, IG, and any PEP (MMR or IG) for nonimmune contacts aged <19 years.

Results

A total of 3409 contacts were identified, of which 208 (6.1%), 274 (8.0%), and 318 (9.3%) met the inclusion criteria for analysis of MMR, IG, and any PEP effectiveness, respectively. Of the contacts included, 44 received MMR PEP and 77 received IG PEP. Effectiveness of MMR PEP was 83.4% (95% confidence interval [CI], 34.4%, 95.8%). No contact who received IG PEP developed measles; effectiveness of IG PEP was 100% (approximated 95% CI, 56.2%, 99.8%). Effectiveness of receiving any PEP (MMR or IG) was 92.9% (95% CI, 56.2%, 99.8%).

Conclusions

Contacts who received PEP were less likely to develop disease. Our findings support current recommendations for administration of PEP following exposure to measles. These results highlight the importance of a rapid public health outbreak response to limit measles transmission following case identification.

Epidemiology and Relative Severity of Influenza Subtypes in Singapore in the Post-Pandemic Period from 2009 to 2010

Abstract

Background

After 2009, pandemic influenza A(H1N1) [A(H1N1)pdm09] cocirculated with A(H3N2) and B in Singapore.

Methods

A cohort of 760 participants contributed demographic data and up to 4 blood samples each from October 2009 to September 2010. We compared epidemiology of the 3 subtypes and investigated evidence for heterotypic immunity through multivariable logistic regression using a generalized estimating equation. To examine age-related differences in severity between subtypes, we used LOESS (locally weighted smoothing) plots of hospitalization to infection ratios and explored birth cohort effects referencing the pandemic years (1957; 1968).

Results

Having more household members aged 5–19 years and frequent public transport use increased risk of infection, while preexisting antibodies against the same subtype (odds ratio [OR], 0.61; P = .002) and previous influenza infection against heterotypic infections (OR, 0.32; P = .045) were protective. A(H1N1)pdm09 severity peaked in those born around 1957, while A(H3N2) severity was least in the youngest individuals and increased until it surpassed A(H1N1)pdm09 in those born in 1952 or earlier. Further analysis showed that severity of A(H1N1)pdm09 was less than that for A(H3N2) in those born in 1956 or earlier (P = .021) and vice versa for those born in 1968 or later (P < .001), with no difference in those born between 1957 and 1967 (P = .632).

Conclusions

Our findings suggest that childhood exposures had long-term impact on immune responses consistent with the theory of antigenic sin. This, plus observations on short-term cross-protection, have implications for vaccination and influenza epidemic and pandemic mitigation strategies.

Levofloxacin Prophylaxis During Induction Therapy for Pediatric Acute Lymphoblastic Leukemia

Abstract

Background

Infection is the most important cause of treatment-related morbidity and mortality in pediatric patients treated for acute lymphoblastic leukemia (ALL). Although routine in adults with leukemia, antibacterial prophylaxis is controversial in pediatrics because of insufficient evidence for its efficacy or antibiotic choice and concerns about promoting antibiotic resistance and Clostridium difficile infection.

Methods

This was a single-center, observational cohort study of patients with newly diagnosed ALL, comparing prospectively collected infection-related outcomes in patients who received no prophylaxis, levofloxacin prophylaxis, or other prophylaxis during induction therapy on the total XVI study. A propensity score–weighted logistic regression model was used to adjust for confounders.

Results

Of 344 included patients, 173 received no prophylaxis, 69 received levofloxacin prophylaxis, and 102 received other prophylaxis regimens. Patients receiving prophylaxis had longer duration of neutropenia. Prophylaxis reduced the odds of febrile neutropenia, likely bacterial infection, and bloodstream infection by ≥70%. Levofloxacin prophylaxis alone reduced these infections, but it also reduced cephalosporin, aminoglycoside, and vancomycin exposure and reduced the odds of C. difficile infection by >95%. No increase in breakthrough infections with antibiotic-resistant organisms was seen, but this cannot be excluded.

Conclusions

This is the largest study to date of antibacterial prophylaxis during induction therapy for pediatric ALL and the first to include a broad-spectrum fluoroquinolone. Prophylaxis prevented febrile neutropenia and systemic infection. Levofloxacin prophylaxis also minimized the use of treatment antibiotics and drastically reduced C. difficile infection. Although long-term antibiotic-resistance monitoring is needed, these data support using targeted prophylaxis with levofloxacin in children undergoing induction chemotherapy for ALL.

Clinical Trials Registration

NCT00549848

Effectiveness of Intramuscular Immunoglobulin in Unvaccinated Family Members After Household Measles Exposure

To the Editor—The efficacy of intramuscular immunoglobulin (IGIM) after measles exposure in patients weighing >30 kg may be decreased, because these patients may not receive an adequate dose of measles antibodies from the maximum dose. The Advisory Committee on Immunization Practices and the California Department of Public Health (CDPH) recommend IGIM for measles prophylaxis if it can be administered within 6 days of exposure [1, 2]. The CDPH recommends 0.5 mL/kg of IGIM with a maximal dose of 15 mL to unvaccinated children who weigh <30 kg. There is no recommendation to administer IGIM to persons weighing >30 kg, presumably because they may not receive a sufficient amount of measles antibodies from the maximum dose of 15 mL [2]. We report the effectiveness of IGIM after household exposure to measles in 2 unvaccinated family members weighing >30 kg.

Reply to Vos et al

To the Editor—Vos et al correctly point out that only 3 studies with reverse transcription polymerase chain reaction (RT-PCR)–based tests were included in our systematic review and metaanalysis. We were also surprised that despite the increasing popularity and rapid implementation of PCR-based rapid tests, only 3 high-quality studies with PCR-based methods that at that time met the inclusion criteria for our systematic review could be incorporated. RT-PCR methods may have great potential as future rapid tests, but implementation of PCR-based rapid tests should be based on data from high-quality studies. Therefore, we encourage the planning of high-quality evaluations of these tests, not only for diagnostic accuracy but also for clinical feasibility [1]. Pointing out possible drawbacks of a specific technique merely reflects our critical view, not a pessimistic attitude toward the future of rapid (PCR) testing. On the contrary, our aim was to encourage this field of research by our review and by expressing our opinion that "true" point-of-care testing requires novel strategies on logistics. In this context, the value of nonmolecular tests should not be underestimated.

Rapid Tests for Common Respiratory Viruses

To the Editor—In the May 2017 issue of Clinical Infectious Diseases, Bruning and colleagues published a detailed review on currently available rapid tests for common respiratory viruses [1]. Based on the pooled estimates of 179 rapid tests from 125 studies, the authors concluded that the sensitivity of rapid tests for respiratory viruses is low.

The Times They Are A-Changin’: Time-Dependent Exposures and Time-Dependent Confounders

To the Editor—We read with great interest the study by Violi et al [1], which investigated the incidence of cardiovascular events (CVEs) after community-acquired pneumonia (CAP), and subsequently estimated the association between CVEs and mortality. The authors concluded that the occurrence of CVEs is associated with a 5-fold increase in 30-day mortality (adjusted hazard ratio, 5.49; 95% confidence interval, 2.91–10.37). This finding could have important clinical implications and therefore it is essential that it be quantified accurately. In this respect we would like to point out 2 issues ignored in the statistical analysis, which could substantially bias the current estimate: time-dependency of the exposure and time-dependent confounders.

Reply to Frencken et al

To the Editor—We thank Dr Frencken and his colleagues [1] for their interesting comments regarding a recently issued article where we analyzed the rate of cardiovascular events (CVEs) in a population affected by community-acquired pneumonia (CAP). In particular, we found that, in a population of 1182 patients hospitalized with CAP, CVEs including myocardial infarction, stroke, heart failure, atrial fibrillation, and cardiovascular death occurred in approximately 30% of patients within 30 days of their admission and that such complications were associated with 30-day mortality [2]. Frencken et al [1] question that we treated CVEs as time-fixed exposure and did not consider the time-dependency of CVEs, which could inflate the risk in the CVE group. Accordingly, we reanalyzed CVEs as a time-dependent covariate and recalculated their impact on mortality in a new Cox model analysis, which confirmed the association between CVEs and mortality (hazard ratio [HR], 4.76; 95% confidence interval [CI], 3.14–7.21; P < .001). The association remained significant when the model was adjusted for age, pneumonia severity score, and comorbidities (HR, 2.52; 95% CI,1.61–3.97; P < .001).

Comparison of Efficacy of Antimicrobial Agents Among Hospitalized Patients With Mycoplasma pneumoniae Pneumonia in Japan During Large Epidemics of Macrolide-Resistant M. pneumoniae Infections: A Nationwide Observational Study

Abstract

Background

Mycoplasma pneumoniae strains with resistance to macrolides have been spreading worldwide. Here, we aimed to clarify which antimicrobial agent is a better treatment for patients with M. pneumoniae pneumonia in a setting with large epidemics of macrolide resistance.

Methods

Adult patients hospitalized with laboratory-confirmed M. pneumoniae pneumonia from 2010 to 2013 were identified from the Japanese Diagnosis Procedure Combination national database. Drug switching, length of stay (LOS), 30-day mortality, and total costs for patients who underwent macrolide, quinolone, and tetracycline therapy were compared using propensity score analyses.

Results

Eligible patients (N = 1650) from 602 hospitals were divided into the macrolide group (n = 508), quinolone group (n = 569), or tetracycline group (n = 573). We found that 52.8%, 21.8%, and 38.6% of patients in the macrolide, quinolone, and tetracycline groups, respectively, had to switch drugs (P < .0001). There was no significant difference in the LOS and the 30-day mortality rates among these 3 groups. Cost was highest in the quinolone group (P = .0062). The propensity score-matched pairs (n = 487×2) generated from the quinolone and tetracycline groups also showed a lower proportion of patients who require switches in the quinolone group than in the tetracycline group (21.2% vs 39.6%, P < .0001) but not in the LOS, mortality, and cost.

Conclusions

There were no significant differences in the LOS and mortality among any antimycoplasmal drugs as initial treatment for hospitalized M. pneumoniae pneumonia patients despite the lower switching rate in the quinolone group.

Effectiveness of Masks and Respirators Against Respiratory Infections in Healthcare Workers: A Systematic Review and Meta-Analysis

Abstract

This systematic review and meta-analysis quantified the protective effect of facemasks and respirators against respiratory infections among healthcare workers. Relevant articles were retrieved from Pubmed, EMBASE, and Web of Science. Meta-analyses were conducted to calculate pooled estimates. Meta-analysis of randomized controlled trials (RCTs) indicated a protective effect of masks and respirators against clinical respiratory illness (CRI) (risk ratio [RR] = 0.59; 95% confidence interval [CI]:0.46–0.77) and influenza-like illness (ILI) (RR = 0.34; 95% CI:0.14–0.82). Compared to masks, N95 respirators conferred superior protection against CRI (RR = 0.47; 95% CI: 0.36–0.62) and laboratory-confirmed bacterial (RR = 0.46; 95% CI: 0.34–0.62), but not viral infections or ILI. Meta-analysis of observational studies provided evidence of a protective effect of masks (OR = 0.13; 95% CI: 0.03–0.62) and respirators (OR = 0.12; 95% CI: 0.06–0.26) against severe acute respiratory syndrome (SARS). This systematic review and meta-analysis supports the use of respiratory protection. However, the existing evidence is sparse and findings are inconsistent within and across studies. Multicentre RCTs with standardized protocols conducted outside epidemic periods would help to clarify the circumstances under which the use of masks or respirators is most warranted.

Surveillance for Q Fever Endocarditis in the United States, 1999–2015

Abstract

Background

Q fever is a worldwide zoonosis caused by Coxiella burnetii. In some persons, particularly those with cardiac valve disease, infection with C. burnetii can cause a life-threatening infective endocarditis. There are few descriptive analyses of Q fever endocarditis in the United States.

Methods

Q fever case report forms submitted during 1999–2015 were reviewed to identify reports describing endocarditis. Cases were categorized as confirmed or probable using criteria defined by the Council for State and Territorial Epidemiologists (CSTE). Demographic, laboratory, and clinical data were analyzed.

Results

Of 140 case report forms reporting endocarditis, 49 met the confirmed definition and 36 met the probable definition. Eighty-two percent were male and the median age was 57 years (range, 16–87 years). Sixty-seven patients (78.8%) were hospitalized, and 5 deaths (5.9%) were reported. Forty-five patients (52.9%) had a preexisting valvulopathy. Eight patients with endocarditis had phase I immunoglobulin G antibody titers >800 but did not meet the CSTE case definition for Q fever endocarditis.

Conclusions

These data summarize a limited set of clinical and epidemiological features of Q fever endocarditis collected through passive surveillance in the United States. Some cases of apparent Q fever endocarditis could not be classified by CSTE laboratory criteria, suggesting that comparison of phase I and phase II titers could be reexamined as a surveillance criterion. Prospective analyses of culture-negative endocarditis are needed to better assess the clinical spectrum and magnitude of Q fever endocarditis in the United States.

Incidence, Risk Factors and Outcome of Pre-engraftment Gram-Negative Bacteremia After Allogeneic and Autologous Hematopoietic Stem Cell Transplantation: An Italian Prospective Multicenter Survey

Abstract

Background

Gram-negative bacteremia (GNB) is a major cause of illness and death after hematopoietic stem cell transplantation (HSCT), and updated epidemiological investigation is advisable.

Methods

We prospectively evaluated the epidemiology of pre-engraftment GNB in 1118 allogeneic HSCTs (allo-HSCTs) and 1625 autologous HSCTs (auto-HSCTs) among 54 transplant centers during 2014 (SIGNB-GITMO-AMCLI study). Using logistic regression methods. we identified risk factors for GNB and evaluated the impact of GNB on the 4-month overall-survival after transplant.

Results

The cumulative incidence of pre-engraftment GNB was 17.3% in allo-HSCT and 9% in auto-HSCT. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most common isolates. By multivariate analysis, variables associated with GNB were a diagnosis of acute leukemia, a transplant from a HLA-mismatched donor and from cord blood, older age, and duration of severe neutropenia in allo-HSCT, and a diagnosis of lymphoma, older age, and no antibacterial prophylaxis in auto-HSCT. A pretransplant infection by a resistant pathogen was significantly associated with an increased risk of posttransplant infection by the same microorganism in allo-HSCT. Colonization by resistant gram-negative bacteria was significantly associated with an increased rate of infection by the same pathogen in both transplant procedures. GNB was independently associated with increased mortality at 4 months both in allo-HSCT (hazard ratio, 2.13; 95% confidence interval, 1.45–3.13; P <.001) and auto-HSCT (2.43; 1.22–4.84; P = .01).

Conclusions

Pre-engraftment GNB is an independent factor associated with increased mortality rate at 4 months after auto-HSCT and allo-HSCT. Previous infectious history and colonization monitoring represent major indicators of GNB.

Clinical Trials registration

NCT02088840.

TXNDC5 Contributes to Rheumatoid Arthritis by Down-regulating IGFBP1 Expression

Summary

The thioredoxin domain-containing 5 (TXNDC5) gene is associated with susceptibility to rheumatoid arthritis (RA) and exhibits increased expression in the synovial tissues. TXNDC5 is also strongly associated with diabetes, a metabolic disease characterized by interrupted insulin signaling. This study investigated whether TXNDC5 contributes to RA via the insulin signaling pathway. In the study, RA synovial fibroblast-like cells (RASFs) transfected with an anti-TXNDC5 small interfering RNA (siRNA) were analyzed with an Insulin Signaling Pathway RT² Profiler PCR Array and an Insulin Resistance RT² Profiler PCR Array. The PCR arrays detected significantly increased expression of insulin-like growth factor binding protein 1 (IGFBP1) in RASFs with suppressed TXNDC5 expression. The result was verified using real-time PCR and western blot analyses. Significantly elevated IGFBP1 expression and decreased IL-6 secretion were also detected in culture medium of transfected RASFs. Furthermore, decreased IGFBP1 mRNA and protein expression levels were detected in RA synovial tissues. Additionally, significantly increased apoptosis and decreased cell proliferation and cell migration were observed in RASFs transfected with the anti-TXNDC5 siRNA, whereas transfection with the anti-IGFBP1 siRNA or a mixture of the anti-IGFBP1 and anti-TXNDC5 siRNAs restored normal cell proliferation, migration and IL-6 level in RASFs. Insulin-like growth factor (IGF) has potent pro-survival and anti-apoptotic functions, and IGFBP1 can suppress IGF activity. Based on the results of the present study, we suggest that TXNDC5 contributes to abnormal RASF proliferation, migration and IL-6 production by inhibiting IGFBP1 expression. This article is protected by copyright. All rights reserved.

Detection of virulence-related genes in Lactococcus garvieae and their expression in response to different conditions

Abstract

Lactococcus garvieae has emerged as an important zoonotic pathogen. However, information regarding mechanisms and factors related to its pathogenicity is lacking. In the present study, we investigated the distribution and functionality of genes related to virulence factors in L. garvieae strains isolated from different niches (diseased fish, humans, meat and dairy products, vegetables), using both post-genomic and genotypic analysis. Putative genes encoding hemolysin, fibronectin-binding protein, and penicillin acylase were detected in all analyzed genomes/strains. Their expression was significantly induced by bile salt stress. Putative genes encoding bile salt hydrolase were found in a few strains from dairy and human sources, as well as the mobilizable tet genes. Finally, all genomes possessed a folate gene cluster, in which mutations in the dihydropteroate synthase gene (folP) could be related to sulfonamide resistance. To the best of our knowledge, this is the first study aimed to explore the pathogenic potential of L. garvieae through the analysis of numerous L. garvieae genomes/strains, coming from different sources. This approach allowed the detection of virulence-related genes not yet investigated in the species and the study of their expression after exposure to different environmental stresses. The results obtained suggest a virulence potential in some L. garvieae strains that can be exploited for survival in the human gastrointestinal tract.

Effect of hyperbaric air on endotoxin from Bacteroides fragilis strains

Abstract

The aim of the project was to determine any effect of hyperbaric air on Bacteroides fragilis strains cultivated under hyperbaric conditions. Previously, it was hypothesized that there was a correlation between the presence of Bacteroides bacteria in patients preferring a meaty diet and cancer of the small intestine, and particularly of the large intestine and rectum. With respect to the fact that Bacteroides fragilis (BAFR) group are important producers of endotoxins, measurement and statistical evaluation of endotoxin production by individual strains of isolated Bacteroides species were used to compare bacteria isolated from various clinical samples from patients with colon and rectum cancer in comparison with strains isolated from other non-cancer diagnoses. Endotoxin production was proven by quantitative detection using the limulus amebocyte lysate (LAL) test in EU/mL. Production of endotoxins in these bacteria cultured under hyperbaric air conditions was higher than those strains cultured under normobaric anaerobic conditions. But these differences in endotoxin production were not statistically significant (t test with log-transformed data, p value = 0.0910). Based on a two-tier t test for lognormal data, it is possible to cautiously conclude that a statistically significant difference was found between endotoxin production by Bacteroides fragilis strains isolated from non-carcinoma diagnoses (strains (1–6) and strains isolated from colorectal carcinoma diagnoses (strains 7–8; Wilcoxon non-parametric test p = 0.0132; t test = 0.1110; t test with log-transformed data, p value = 0.0294).

Behandlungsalgorithmus CUP

Metals in Diplodus sargus cadenati and Sparisoma cretense —a risk assessment for consumers

Abstract

The increases in urbanization, demography and industrial activity, along with growing human needs which exploit the resources of the planet, have exponentially exacerbated pollution. In particular, the discharge of heavy metals into the marine ecosystem is a problem of global magnitude, as this may damage the diversity of marine species and ecosystems because of their toxicity, long persistence and bioaccumulation. Consequently, it is necessary to carry out an assessment of the risk of human exposure from the consumption of marine species potentially exposed to this type of pollutants. In the present study, the levels of toxic heavy metals (Cd, Pb and Al) as well as trace and essential metals (B, Ba, Co, Cu, Cr, Fe, Li, Mn, Mo, Ni, Sr, V and Zn) and macronutrients (Ca, K, Mg, Na) have been quantified in two species of fish for human consumption. In order to do this, a total of 80 muscle samples and 80 liver samples, belonging to two species of osteichthyes (bony fish), Diplodus sargus cadenati and Sparisoma cretense, were analyzed. The specimens studied were captured on the north coast of Gran Canaria (Canary Islands) using recreational fishing techniques. As they caught from the shore, the data obtained respond to the need to assess the toxic levels in two representative species of artisanal and recreational fishing in the area. The risk assessment indicated that these two fish species are safe for the average consumer; however, if the livers are frequently consumed, there may be potential risks because they exceed the Admissible Daily Intakes for Pb and Cd.

Benchmarking the scientific research on wastewater-energy nexus by using bibliometric analysis

Abstract

With an exponential increase in urbanization and industrialization, water pollution is an inevitable consequence of relatively lagging wastewater treatment facilities. The conventional activated sludge process for wastewater treatment primarily emphasizes the removal of harmful substances to maintain increasingly stringent effluent discharged standards, which is considered an energy-intensive technique. Therefore, innovative and sustainable wastewater treatment should pay more attention to energy and resource recovery in dealing with fossil fuel depletion, global-scale energy security, and climate change. A bibliometric analysis was applied to trace wastewater-energy nexus-related research during the period 1991 to 2015, with respect to the Science Citation Index EXPANDED (SCI-EXPANDED) database. Journal of Hazardous Materials, ranking 1st in h-index (79), was the most productive journal (431, 4.5%) during the same time, followed by International Journal of Hydrogen Energy (422, 4.4%) and Water Research (393, 4.1%) journal, the latter owning a topmost journal impact factor. Though, China (2154, 22.5%) was the most productive country, while the USA with highest h-index (88) was the favorest collaborative country. The Chinese Academy of Sciences, China (241, 2.5%) produced the maximum publications. A novel method called "word cluster analysis" showed that the emerging sustainable processes and novel renewable energy application are applied in response to the desire for a net wastewater-energy nexus system. Based on different wastewater types, the emerging energy and sources recovery treatment processes of Anammox, anaerobic digestion, and microbial fuel cells gained extensive innovation. Evaluation indicators including sustainability, life cycle assessment, and environmental impact were appropriately used to dissert feasibility of the novel treatment methods in regard of renewable energy utilization, energy savings, and energy recovery. The transformation of the new concept of "broaden income source, economize on expenditures and exploit inner potential" should be generalized in order to achieve an environmentally sustainable development of wastewater-energy nexus system.

Pemphigoid gestationis: current perspectives