Differential Associations for Salivary Sodium, Potassium, Calcium, and Phosphate Levels with Carotid Intima Media Thickness, Heart Rate, and Arterial Stiffness

Salivary biomarkers may offer a noninvasive and easy sampling alternative in cardiovascular risk evaluation. The aim of the present study was to establish associations of salivary potassium, sodium, calcium, and phosphate levels with the cardiovascular phenotype determined by carotid ultrasound and carotid-femoral pulse wave velocity and to identify possible covariates for these associations. samples of nonstimulated whole buccal saliva were obtained from subjects with (; 59%) or without (; 41%) hypertension. The potassium concentrations were 10-fold higher in saliva compared with plasma, whereas sodium concentrations exhibited the reverse relation between saliva and blood. There were no significant correlations between the levels of sodium, potassium, or calcium in saliva and plasma. All salivary electrolytes, except sodium, were significantly associated with age. In age-adjusted analyses, salivary potassium was significantly associated with carotid artery intima media thickness (cIMT) and carotid-femoral pulse wave velocity, and these associations were at the limit of significance in multivariate analyses including prevalent cardiovascular disease and risk factors. Body mass index was a significant confounder for salivary potassium. Salivary phosphate was significantly associated with cIMT in the multivariate analysis. Salivary potassium, calcium, and phosphate levels were significantly associated with heart rate in the univariate age-adjusted as well as in two different multivariate models, whereas no significant associations between sodium and heart rate were observed. In conclusion, the differential association of salivary electrolytes with cardiovascular phenotypes indicates that these electrolytes should be further studied for their predictive value as noninvasive biomarkers for cardiovascular risk evaluation.

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Actor-specific risk perceptions and strategies for resilience building in different food systems in Kenya and Bolivia

Abstract

Food system sustainability depends, among other aspects, on the resilience of different components of food systems. By resilience, we mean the ability of a food system to withstand stress and shocks, recover, and adapt to change. In this study, we examined the resilience of food systems, firstly, by compiling the risks perceived by different food system actors in the Santa Cruz Department, Bolivia, and the northwestern Mount Kenya Region, Kenya—two regions that are important to their respective national food supply. Secondly, we evaluated whether and under what circumstances these perceptions translate into adaptive or preventive strategies that benefit food system resilience. Among all actors, the most frequently perceived risks relate to production levels. Further, the many (sometimes contradictory) perceptions of risk and uncertainty among different actor groups do not necessarily translate into adaptation strategies. Reasons for this include structural factors as well as the "risk perception paradox", particularly regarding preventive strategies. However, we also observed many implicit strategies illustrating how different actors develop responses within their possibilities. However, most such strategies were insufficient to mitigate, much less to adapt to, the perceived risks. To build resilience, existing innovative policies need to be enforced in both countries. These include disaster risk reduction programs and programs to reduce the vulnerability of marginalized groups who are crucial to food systems, such as smallholder farmers, pastoralists, and food workers.

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Serum Procalcitonin and Presepsin Levels in Patients with Generalized Pustular Psoriasis

Patients with generalized pustular psoriasis (GPP) often present with symptoms that must be differentiated from sepsis. Procalcitonin (PCT) and presepsin (P-SEP) are widely used as biomarkers for sepsis; therefore, we examined the serum PCT and P-SEP levels in patients with psoriatic diseases. The enrolled patients included 27 with psoriasis vulgaris (PV) (22 males, 5 females; mean age 47.7 years), 12 with psoriatic arthritis (PsA) (8 males, 4 females; mean age 51.3 years), and 15 with GPP (10 males, 5 females; mean age 63.7 years). The mean serum PCT levels in patients with PV, PsA, and GPP were 0.01 ng/mL (25th–75th percentile; 0.00–0.03), 0.013 ng/mL (0.00–0.03), and 0.12 ng/mL (0.05–0.18), respectively; the levels of PCT were higher for patients with GPP than with PV or PsA but were lower than the PCT cutoff value (0.5 ng/mL) for the diagnosis of infection. The mean serum P-SEP levels in patients with PV, PsA, and GPP were 144.9 pg/mL (25th–75th percentile; 78–181), 168.1 pg/mL (124–203), and 479.9 pg/mL (216–581), respectively. Unexpectedly, the levels of P-SEP in the patients with GPP were as high as the P-SEP cutoff value (317 to 647 pg/mL) used for the diagnosis of infection. We also found that neutrophils produced P-SEP, suggesting that the high serum P-SEP levels in patients with GPP might arise at least in part due to the P-SEP derived from neutrophils activated in GPP. Both serum PCT and P-SEP might therefore be useful as novel serum biomarkers for GPP because their levels were decreased by GPP treatments. However, the measurement of PCT might be more useful than the measurement of P-SEP for discriminating between GPP and sepsis.

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Gut microbiome approaches to treat obesity in humans

Abstract

The rising worldwide prevalence of obesity has become a major concern having many implications for the public health and the economy. It is well known that many factors such as lifestyle, increased intake of foods high in fat and sugar and a host's genetic profile can lead to obesity. Besides these factors, recent studies have pointed to the gut microbiota composition as being responsible for the development of obesity. Since then, many efforts have been made to understand the link between the gut microbiota composition and obesity, as well as the role of food ingredients, such as pro- and prebiotics, in the modulation of the gut microbiota. Studies involving the gut microbiota composition of obese individuals are however still controversial, making it difficult to treat obesity. In this sense, this mini-review deals with obesity and the relationship with gut microbiota, summarising the principal findings on gut microbiome approaches for treating obesity in humans.

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Bacterial community activity and dynamics in the biofilm of an experimental hybrid wetland system treating greywater

Abstract

The objectives of this study were to determine the biofilm microbial activity and bacterial community structure and successions in greywater treatment filters and to relate the treatment efficiency to the bacterial community parameters. This 10-month study was performed in a newly established experimental system for domestic greywater treatment that consisted of three parallel vertical flow filters (VFs) followed by a horizontal flow filter (HF). A rapid increase in the bacterial community abundance occurred during the first 85 days of filter operations, followed by a short-term decrease and the stabilization of the 16S rRNA gene copy numbers at average levels of 1.2 × 10⁹ and 3.2 × 10⁸ copies/g dw in VFs and HF, respectively, until the end of the experiment. The dominant bacterial phyla and genera differed between the VFs and HF. The temporal variation in the bacterial community structure was primarily related to the species replacement, and it was significantly affected by the influent organic carbon and nitrogen compounds in the VFs and the ammonia and organic carbon in the HF filters. Despite the differences in the community structure and assembly mechanisms, the temporal dynamics of the bacterial community showed high congruence between the filter types. The treatment efficiency was related to the biofilm bacterial community diversity and abundance and the abundance of certain bacterial genera in the VF filters. The results suggest that the dominant pathway of nitrogen removal by greywater treatment VFs occurs via coupled heterotrophic nitrification and denitrification, while the contribution of aerobic denitrification is temporally variable in these filters.

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Imbalance of peripheral follicular helper T lymphocyte subsets in active vitiligo

Summary

Vitiligo is an autoimmune disease characterized by the presence of several autoantibodies, some of which are directed against melanocyte components and have been shown to be associated with the progression of the disease. However, the mechanism involved in the production of autoantibodies remains unclear. Follicular helper CD4⁺ T cells (TFH) are specialized in B cell activation and antibody production, especially the TFH cell subsets type 2 and type 17. To date, TFH cell subsets have not been studied in human vitiligo. This study in 44 vitiligo patients and 19 healthy controls showed an increase in circulating TFH cells associated with disease clinical progression. A more precise analysis of TFH cell phenotype demonstrated that vitiligo is characterized by populations of peripheral TFH cells responsible for helping B cell function, such as TFH type 2 and type 17 which produce Th2 and TH17‐related cytokines, respectively. These findings suggest a new mechanism involving TFH cell subsets in the pathogenesis of human vitiligo and leading to the production of autoantibodies and disease.

This article is protected by copyright. All rights reserved.

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Issue Information

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Cover Image

The cover image, by Ariyan Mottaghi et al., is based on the Review Article Is there a higher prevalence of tinnitus in patients with temporomandibular disorders? A systematic review and meta‐analysis DOI: 10.1111/joor.12706.

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Quorum sensing between Gram-negative bacteria responsible for methane production in a complex waste sewage sludge consortium

Abstract

Quorum sensing (QS) plays a key role in activating bacterial functions through small molecules called autoinducers. In this study, the QS of Gram-negative bacteria in waste sewage sludge (WSS) was downregulated by adding the quorum quenching enzyme, AiiM lactonase, which cleaved the acyl-homoserine lactone (AHL) autoinducer signals from Gram-negative bacteria, and subsequently methane production was inhibited by over 400%. The pH was lowered after 2 days in the anaerobic fermentation whereas protease activity at the hydrolysis step was almost the same with or without AiiM. The production of acetic acid significantly increased during the fermentation in the presence of AiiM. The bacterial community at day 2 indicated that the population of Gram-positive bacteria increased in the presence of AiiM, and the percentage of Gram-negative bacteria decreased in the WSS containing AiiM. The change in the bacterial community in the presence of AiiM may be due to the different antimicrobial agents produced in the WSS because some of the Gram-positive bacteria were killed by adding the solid-phase extraction (SPE) fraction from the WSS without AiiM. In contrast, the SPE fraction with AiiM had reduced bactericidal activity against Gram-negative bacteria. Thus, bacterial signaling between Gram-negative bacteria is critical for methane production by the microbial consortia.

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Development of a model for food waste composting

Abstract

Worldwide, large amounts of food are wasted every year. Reducing of food waste at European level is taken very seriously and it has been adopted even a target of reducing the amount of food waste in half until 2030. In many countries of the European Union, food wastes are composted, while in countries like Romania, the composting is too little used or not at all, but efforts are being made to apply this process. Food waste composting should take place both at the composting plants and housing level. An important step before starting the composting process is to establish an appropriate recipe. Therefore, the aim of this paper is to develop a composting recipe starting from investigation of food waste like peel and pomace of fruits (apple, banana, orange, and kiwi) and vegetables (potato, cabbage, and carrots) which are very common in waste generated at the housing level. The most important physical-chemical parameters were investigated in this study. Results show that pH of fruit waste is acid (4.0–5.0), while for vegetable waste, the pH is slightly higher (between 6.0 and 6.5). For all types of food waste, a very high moisture content (80–90%) was registered, while the nitrogen content is below 1%. Considering that C/N ratio is one of the most essential parameters, for the process to be carried out in good conditions, we have used regression analysis in order to determine the amounts of fruits and vegetable waste necessary to obtain different C/N ratios.

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Unraveling the sources and fluorescence compositions of dissolved and particulate organic matter (DOM and POM) in Lake Taihu, China

Abstract

Organic matter (OM), a complex entity with diverse functional groups and molecular sizes, has important effects on aquatic systems. We studied the optical compositions and sources of dissolved organic matter (DOM) and particulate organic matter (POM) in Lake Taihu, a large, shallow and eutrophic lake in China. Significant differences in optical compositions and sources occurred between the POM and DOM. The temporal–spatial distribution of the fluorescence indices suggested that the POM in Lake Taihu was mainly from autochthonous sources, but more exogenous characteristics were shown in POM in the river mouths compared with other regions. The chromophoric DOM in Lake Taihu mainly displayed autochthonous characteristics. The POM–DOM PARAFAC model was used to examine OM optical composition and five components were identified, which contained three protein-like components (C1, C2, and C5), a microbial humic-like component (C3), and a terrestrial humic-like component (C4). The POM was dominated by C5 in summer and autumn and C3 in winter and spring, and the DOM was dominated by protein-like components (C1, C2, and C5) through the entire year. The algae-dominated region had a relative higher contribution of tryptophan-like components of POM compared with the macrophyte-dominated region. A conceptual model based on the theory of "four phases of cyanobacteria bloom development" was proposed to fully describe the relationship between POM–DOM exchanges and cyanobacteria bloom development.

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Effects of biochar and dicyandiamide combination on nitrous oxide emissions from Camellia oleifera field soil

Abstract

Greenhouse gas emissions from agricultural soils contribute substantially to global atmospheric composition. Nitrous oxide (N₂O) is one important greenhouse gas induces global warming. Nitrification inhibitors (NI) or biochar can be effective soil N₂O emission mitigation strategies for agricultural soils. However, due to differences in crop physiological traits or agricultural management, the effectiveness of mitigation strategies varies among agricultural systems. Camellia oleifera is a woody oil plant widely grown and requires intensive N input, which will potentially increase N₂O emissions. Thereby, mitigation of N₂O emissions from C. oleifera field soil is vital for sustainable C. oleifera development. Besides NI, incorporation of C. oleifera fruit shell-derived biochar into its soil will benefit waste management and simultaneous mitigation of N₂O emissions but this has not been investigated. Here, we conducted two studies to examine effects of biochar addition and NI (dicyandiamide, DCD) application on N₂O emissions from C. oleifera field soil with different N (urea or NH₄NO₃) and incubation temperatures. Biochar effects on nitrification rates varied among N treatments. Biochar applied in combination with DCD further reduced nitrification rates (for urea treatment, decreased from 1.1 to 0.3 mg kg⁻¹ day⁻¹). Biochar addition consistently increased soil N₂O emissions (for urea treatment, increased from 0.03 to 0.08 ng g⁻¹ h⁻¹) and their temperature sensitivity. DCD application reduced soil N₂O emissions with greater reductions with urea application. In future cultivation of intensively managed C. oleifera gardens, NI should be applied to mitigate N₂O emissions if biochar is added, especially when urea is used.

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Potential Induced Fine‐tuning the Enantioaffinity of Chiral Metal Phases

Concepts leading to single enantiomers of chiral molecules are of crucial importance for many applications, including pharmacology and biotechnology. Recently, mesoporous metal phases encoded with chiral information have been developed. We propose here to fine‐tune the enantioaffinity of such structures by imposing an electric potential, which can influence the electrostatic interactions between the chiral metal and the target enantiomer. This allows increasing the binding affinity and thus the discrimination between two enantiomers. The concept is illustrated by generating chiral encoded metals in a microfluidic channel via the reduction of a platinum salt in the presence of a liquid crystal and L‐tryptophan as a chiral model template. After removal of the template molecules, the modified microchannel retains a pronounced chiral character. Its chiral recognition efficiency can be fine‐tuned by applying a suitable potential to the metal phase. This enables the separation of both components of a racemate flowing through the channel. The approach constitutes a promising and complementary strategy in the frame of chiral discrimination technologies.

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Nucleus‐targeted organoiridium‐albumin conjugate for photoactivated cancer therapy

: A highly phosphorescent organoiridium‐albumin conjugate (Ir1‐HSA) was synthesized by reacting an organo‐iridium complex (Ir1) containing a pendant maleimide with human serum albumin. The phosphorescence of the Ir1‐HSA conjugate is much stronger than the parent iridium complex. Real‐time cellular imaging shows that the conjugate mainly accumulates in the nucleus of cancer cells. The long phosphorescence lifetime and high 1O2 quantum yield of Ir1‐HSA make it a strong candidate for photoactivated cancer therapy. Ir1‐HSA shows remarkable photocytotoxicty in a range of cancer cell lines and tumor spheroids (IC50; 0.8‐5 μM) with an excellent photo‐cytotoxicity index (C50 (dark) / IC50 (light) = 40‐60) while remaining non‐toxic to normal cells and normal‐cell spheroids, even after photo‐irradiation. This organoiridium‐albumin photosensitizer has potential for application in both photoactivated therapy and nucleus staining.

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Salivary Nickel and Chromium Levels in Orthodontic Patients with and Without Periodontitis: a Preliminary Historical Cohort Study

Abstract

Many periodontal patients may need orthodontic treatment. Alterations in oral environment particularly the reduction of pH in periodontal patients could affect metal ion release from orthodontic appliances. However, there is no study on metal ion release in periodontal patients. The aim of this preliminary study was to comparatively evaluate, for the first time, salivary levels of nickel and chromium in periodontal patients (versus healthy controls) under orthodontic treatment for 2 months. In this in vivo study, 40 subjects were evaluated. Patient selection and standardization of orthodontic treatment protocols were prospectively designed and performed. Two groups of n = 20 each (control: healthy orthodontic patients, cohort: orthodontic patients with periodontitis) underwent similar protocols of fixed orthodontic treatment for 2 months. After 2 months, salivary nickel and chromium concentrations of the case and cohort groups were measured using inductively coupled plasma mass spectrometry (ICP-MS). The values were compared between the two groups using t test. There were 10 men and 10 women in each group. The mean age of patients was 34.6 ± 3.6 years old. The salivary level of nickel was 338.2 ± 235.5 ng/ml and 182.8 ± 116.5 ng/ml in the cohort and control groups, respectively (P = 0.0118). The salivary level of chromium was 7.4 ± 3.15 ng/ml in the cohort and 6.35 ± 2.39 ng/ml in the control group (P = 0.2214). Salivary level of nickel might be considerably higher in periodontal patients undergoing 2 months of orthodontic treatment compared to orthodontic patients with healthy gingivae.

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Effects of Selenium-Enriched Yeast Improved Aflatoxin B1-Induced Changes in Growth Performance, Antioxidation Capacity, IL-2 and IFN-γ Contents, and Gene Expression in Mice

Abstract

Sixty Kunming mice were randomly assigned into three groups. Mice in a control group were fed a basal diet, while mice in AFB1 group and AFB1-Se group were fed the basal diet supplemented with 250 μg/kg AFB1 or the basal diet supplemented with 250 μg/kg AFB1 and 0.2 mg/kg selenium as selenium-enriched yeast, respectively. On day 30 of the experiment, growth performance, glutathione peroxidase (GSH-Px) activities, total antioxidant capacity (T-AOC) levels, and malondialdehyde (MDA) contents in liver, interleukin-2 (IL-2), and interferon-γ (IFN-γ) contents in serum, and cytochrome P3a11 (Cyp3a11), IL-2, IFN-γ, and GSH-Px1 mRNA levels in liver were determined. The results showed that final weights, weight gains, T-AOC levels, GSH-Px1, and IFN-γ mRNA levels in AFB1-Se group and control group were higher or significantly higher than those in AFB1 group (P < 0.05 or P < 0.01), respectively. Body length gains in AFB1 group were lower than those in the control group (P < 0.05), while there was no significant difference between the AFB1-Se and control groups (P > 0.05). IL-2 contents and liver IL-2 mRNA levels in AFB1-Se group were significantly higher than those in the AFB1 group and control group (P < 0.01), and IL-2 contents in the control group were also significantly higher than those in the AFB1 group (P < 0.01). IFN-γ contents in AFB1-Se group and AFB1 group were significantly higher than those in control group (P < 0.01), while IFN-γ contents in AFB1-Se group were significantly lower than those in AFB1 group (P < 0.01). Cyp3a11 mRNA levels in AFB1-Se group and AFB1 group were significantly higher than those in the control group (P < 0.01). The results indicated that selenium-enriched yeast could partly reduce the toxicity induced by AFB1 in mice, including improving growth performance, antioxidation capacity, IL-2 and IFN-γ contents, and enhancing IL-2, IFN-γ, and GSH-Px1 mRNA levels.

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Occupational cannabis exposure and allergy risks

Objectives

Cannabis allergy has mainly been described following recreational use but some cases also point to cannabis sensitisation as a result of occupational exposure. As a consequence, little is known on the prevalence and clinical phenotype of occupational cannabis allergy. Therefore, this study aims to explore the allergy-associated health risks of occupational cannabis exposure in Belgian police force personnel.

Methods

81 participants, active in the police force, reporting regular occupational cannabis exposure during the past 12 months, were included. History was combined with a standardised questionnaire on allergies and cannabis exposure.Basophil activation tests (BATs) with a crude cannabis extract and rCan s 3 were performed. In addition, specific (s)IgE rCan s 3 as well as sIgE to house dust mite, six pollen and three mould allergens were quantified.

Results

Although 42% of the participants reported respiratory and/or cutaneous symptoms on occupational cannabis exposure, all cannabis diagnostics were entirely negative, except one symptomatic case demonstrating a borderline result. Furthermore, there is no significant difference between the groups with and without symptoms on cannabis exposure in terms of allergenic sensitisations.

Conclusions

The origins of the reported respiratory and cutaneous symptoms during cannabis exposure remain elusive but are probably due to non-immune reactions. It should be noted that the study was volunteer-based possibly reflecting an excessive number of symptomatic individuals. Nevertheless, as only one participant reported using fully protective gear, much improvement is needed for reducing the number of symptoms reported on duty, independent of their origin.

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Classification of the superior angle of the scapula and its correlation with the suprascapular notch: a study on 303 scapulas

Abstract

Purpose

The aims of this study had been to classify the superior angle of the scapula based on morphological features, and to investigate its correlation with the suprascapular notch.

Methods

303 samples of Chinese dried scapular specimens were collected from the Department of anatomy, Southwest Medical University. According to the anatomical morphological characteristics of the superior angle of the scapula, the morphological classification was performed to explore its correlation with the suprascapular notch (SSN).

Results

The superior angle of the scapula was classified into three types (Hilly shape, Mountain Peak shape and Chimney shape). There were 143 cases of Hilly shape (47.20%), 144 cases of Mountain shape (47.52%), and 16 cases of Chimney shape (5.28%). The angle of Hilly shape (93.36° ± 7.76°) was significantly larger than the Mountain Peak shape (86.60° ± 6.61°) and the Chimney shape (86.22° ± 7.20°), and the difference was statistically significant (P < 0.05). The type I–III of Rengachary's classification to SSN was low risk of suprascapular nerve entrapment, while the type IV–VI was high risk of suprascapular nerve entrapment. Compared with the Mountain Peak shape and the Chimney shape, the Hilly shape corresponds to more types I–III of suprascapular notch but to fewer types IV–VI (P < 0.05).

Conclusions

The superior angle of the scapula was divided into three types: Hilly shape (47.20%), Mountain Peak shape (47.52%) and Chimney shape (5.28%). The Mountain Peak shape might be more likely to result in inability of the levator muscle with acute or chronic overload mechanisms, and the risk of suprascapular nerve entrapment in Mountain peak shape was higher than that of Hilly shape. And, it might have a potential effect on neck pain.

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Induction of apoptosis-like death by periplanetasin-2 in Escherichia coli and contribution of SOS genes

Abstract

Periplanetasin-2 is a 15-mer antimicrobial peptide (AMP), derived from the American cockroach Periplaneta americana. This novel AMP exhibits potent antibacterial effect against several pathogenic bacteria including Escherichia coli. Distinct from the targeting cell membrane, which is the general antibacterial mechanism of AMP, periplanetasin-2 exerts its antibacterial activity via apoptosis-like death, which is physiologically and mechanistically similar to eukaryotic apoptosis. E. coli cells treated with periplanetasin-2 showed features of apoptosis in a concentration-dependent manner, such as membrane depolarization, DNA fragmentation, caspase-like protein activation, and phosphatidylserine externalization. These physiological changes were attenuated by pretreatment with the reactive oxygen species (ROS) scavenger, which demonstrates that periplanetasin-2 induced apoptosis-like death in E. coli by generating ROS. In addition, periplantasin-2-induced apoptotic death was affected by SOS response components. In the absence of RecA, an essential protein for SOS response, apoptosis did not occur and the antibacterial activity of periplanetasin-2 was decreased. In contrast, deletion of the SOS gene dinF caused higher ROS accumulation and apoptotic features were detected. Collectively, these results indicate that the antibacterial mechanism of periplanetasin-2 is ROS-induced apoptosis-like death, which requires RecA for proceeding it, and the role of DinF is assumed to contribute to the ROS defense SOS response.

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Explore the influence mechanism of carbon emissions decline on energy intensity with two-layer factor decomposition method in Beijing-Tianjin-Hebei region

Abstract

Understanding the intrinsic mechanism behind changes on energy intensity provides insights about reducing carbon emissions and promoting the sustainable development of Beijing-Tianjin-Hebei (BTH) region. Although various studies have found a causal relationship between energy intensity and energy-related carbon emissions, the internal mechanisms are still unclear. This paper presents a comprehensive analysis of the impact of energy intensity on carbon emissions from 2005 to 2015. With an association established between logarithmic mean Divisia index (LMDI) and generalized Fisher index (GFI), two-layer factor decomposition model is proposed to explore the factor analysis in-depth. (1) LMDI method proves that energy intensity is the main contributor that reduces carbon emissions in BTH. (2) GFI model further decomposes energy intensity into five effects, namely energy substitution, technology progress, labor productivity, capital substitution, and labor-capital resources allocation. (3) The results reveal that the effect of capital-energy substitution in declining energy intensity surpasses technology progress. (4) Energy-labor substitution has increased energy intensity, while energy-energy substitution is negligible. For the coordinate development of BTH, the government should aim at energy intensity and attach importance to encouraging entrepreneurship, accelerating the construction of carbon trading market, allocating resources rationally, and guiding the capital flow into energy-efficient direction.

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Endodontic sealers based on calcium silicates: a systematic review

Abstract

Recently, sealers based on calcium silicates were developed as a new class of endodontic sealers. Inspired by the excellent sealing ability and biocompatibility of calcium silicate-based cements, these sealers establish a biological point of view on the obturation of root canals. No longer, the bacteria-tight seal against reinfection of the root canal is the only goal of root canal obturation. Antibacterial properties as well as bioactive inducement of periapical healing and hard tissue formation are added to the portfolio of sealers. Ready-to-use sealers consisting of only one component with a need for external water supply from, e.g., body fluid and two components sealers with internal water supply were introduced to the market. Both of these material types have the same setting reactions in common whereby a hydration reaction of the calcium silicate is followed by a precipitation reaction of calcium phosphate. Though the available sealers are all based on calcium silicates, they consist of different compositions. Due to this aspect, differences in their physical and chemical properties as well as in their in vitro characteristics were described. Studies addressing the clinical impact of calcium silicate-based sealers on outcome are still sparse. The bioactive potential of sealers based on calcium silicates is a consequence of the slight solubility of these materials even after setting, but solubility of the sealer might also compromise the quality of sealing a root canal against regrowth and reinfection. Further clinical investigations are required to evaluate the clinical relevance of the gulf between bioactivity and solubility.

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PTP1B markedly promotes breast cancer progression and is regulated by miR-193a-3p.

Related Articles

PTP1B markedly promotes breast cancer progression and is regulated by miR-193a-3p.

FEBS J. 2018 Dec 07;:

Authors: Yu M, Liu Z, Liu Y, Zhou X, Sun F, Liu Y, Li L, Hua S, Zhao Y, Gao H, Zhu Z, Na M, Zhang Q, Yang R, Zhang J, Yao Y, Chen X

Abstract
The protein tyrosine phosphatase PTP1B, which is encoded by PTPN1, is a ubiquitously expressed non-receptor protein tyrosine phosphatase. PTP1B has long been known to negatively regulate insulin and leptin receptor signalling. Recently, it was reported to be aberrantly expressed in cancer cells and to function as an important oncogene. In this study, we found that PTP1B protein levels are dramatically increased in breast cancer tissues and that PTP1B promotes the proliferation, and suppresses the apoptosis, of both HER2-positive and triple-negative breast cancer cell lines. Bioinformatics analysis identified that the miRNA, miR-193a-3p, might potentially target PTP1B. We demonstrate that miR-193a-3p regulates PTP1B in breast cancer cells and that it regulates the proliferation and apoptosis of breast cancer cells by targeting PTP1B, both in vitro and in vivo. In conclusion, this study confirms that PTP1B acts as an oncogene in breast cancer and demonstrates that miR-193a-3p can serve as a tumour suppressor gene in breast cancer by targeting PTP1B. This article is protected by copyright. All rights reserved.

PMID: 30548198 [PubMed - as supplied by publisher]

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Phase III trials examining the efficacy of cetirizine ophthalmic solution 0.24% compared to vehicle for the treatment of allergic conjunctivitis in the conjunctival allergen challenge model

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Mental time travel and functional daily life activities in neglect patients: Recovery effects of rehabilitation by prism adaptation

Publication date: Available online 14 December 2018

Source: Cortex

Author(s): Filomena Anelli, Stefano Avanzi, Alessio Damora, Mauro Mancuso, Francesca Frassinetti

Abstract

Recent neuropsychological evidence put forward impaired ability in processing particular aspects of time, such as Mental Time Travel (MTT), in brain damaged patients exhibiting a deficit of spatial attention (i.e., neglect) and the possibility to recover this MTT deficit through a manipulation of spatial attention by prism adaptation (PA). The aim of the present study was twofold. First, we explored whether the neglect patients' impairment in MTT is linked with an impairment in functional competences, such as processing temporal duration of everyday activities, motor abilities and independence in daily living. Second, we focused on rehabilitation, investigating the long-term duration of the benefits induced by a PA treatment on both mental time travel and the above-mentioned functional abilities.

To these aims, neglect patients were submitted to a MTT task, as well as to a battery of tests assessing spatial attention, estimation of time duration, motor competence and independence in activities of daily living. All tests were performed before, at the end, and one week after 10 daily sessions of PA treatment inducing a leftward shift of spatial attention.

Results suggest that neglect patients' impairment in MTT ability correlates with spatial attention deficit and with difficulties in producing reasonable temporal estimation of daily life activities. Crucially, the PA treatment induces a long-lasting and stable amelioration of MTT, spatial attention and functional competences.

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Visual search pattern during free viewing of horizontally flipped images in patients with unilateral spatial neglect

Publication date: Available online 14 December 2018

Source: Cortex

Author(s): Satoko Ohmatsu, Yusaku Takamura, Shintaro Fujii, Kouhei Tanaka, Shu Morioka, Noritaka Kawashima

Abstract

Eye tracking is an effective tool for identifying behavioural aspects of unilateral spatial neglect (USN), which is a common neurological syndrome that develops after a right hemisphere lesion. Here, we attempted to elucidate how the neglect symptom affects the symmetry of the gaze pattern, by performing an analysis of gaze distribution during the free viewing of a pair of horizontally flipped images. Based on their Behavioural Inattention Test (BIT) scores, 41 patients with right-hemisphere damage were classified into those with USN (n=27) and those without USN (right hemisphere damaged [RHD]; n=14). Eye movement was recorded while the patients viewed six pairs of horizontally flipped images on a computer display. A pair of flipped images has both similar and consistent elements, as well as a reversed spatial location of objects (right-left). We calculated the gaze distribution, extent of gaze shift, total gaze distance, and gaze velocity in each direction. Our results demonstrated a significantly larger rightward gaze shift in the USN group, which showed a significant correlation with the BIT score. More importantly, the extent of gaze shift and total gaze distance were similarly modulated by the contents of the displayed images in both the USN and RHD groups. Our findings suggest that analyses of gaze distribution during the free viewing of a pair of horizontally flipped images have the potential to precisely reveal neglect behaviour, and our results provide important implications for rehabilitation.

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Exposure to methylphenidate in adolescence and adulthood modulates cross-sensitization to amphetamine in adulthood in three genetically variant female rat strains

Publication date: Available online 14 December 2018

Source: Behavioural Brain Research

Author(s): Natasha Kharas, Pamela Yang, Daniel Castro-Alvarado, Kevelyn Rose, Nachum Dafny

Abstract

Attention Deficit Hyperactivity Disorder (ADHD) is a developmental, behavioral disorder that is characterized by patterns of impulsivity and limited attention. Stimulants, such as methylphenidate (MPD) and amphetamine (Amph), are utilized as first-line agents in the treatment of ADHD. While Amph is known elicit dependence, MPD is not. Interdependence between MPD and Amph is a growing concern. Therefore, it is important to explore this interaction in animal models to gain insight on its mechanisms. In experimental studies, drugs that elicit behavioral sensitization and cross-sensitization in animals are considered to have the potential to elicit dependence. This study evaluated whether chronic repetitive MPD exposure in adolescence and/or adulthood in various genetic strains of female rats elicits behavioral sensitization as well as cross-sensitization with Amph. We used three strains: SHR (ADHD model), WKY, and SD rats. The three rat strains were exposed to chronic MPD in their adolescence and adulthood or exposed to chronic MPD only in adulthood. When the female rats were treated with MPD only in adulthood, the SHR strain exhibited cross-sensitization to Amph but the WKY and SD strains did not. Whereas, when the female rats were pretreated with MPD in adolescence and adulthood, the SHR and WKY strains exhibited cross-sensitization response to Amph, but the SD strain did not. This study showed that the genetic strain and age of exposure to MPD plays a crucial role in cross-sensitization to Amph in female rodents. Furthermore, we showed that genetics associated with ADHD pre-dispose animals to dependence between drugs even if the exposure starts in adulthood compared to control strains that did not show dependence with adult only MPD exposures. Genetic variability, age of initial drug exposure, and sex of the subject are key variables that should be accounted in studies that explore effects of psychostimulants.

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Role of N-methyl-D-aspartate receptors in the long-term effects of repeated social defeat stress on the rewarding and psychomotor properties of cocaine in mice

Publication date: Available online 14 December 2018

Source: Behavioural Brain Research

Author(s): MP García-Pardo, C Calpe-López, J Miñarro, MA Aguilar

Abstract

Exposure to social stress increases the vulnerability of experimental animals to the rewarding effects of cocaine and it has been suggested that the glutamatergic system could be involved in these effects of stress. The aim of this work is to determine the role of N-methyl-D-aspartate (NMDA) glutamate receptors in the influence of social stress on the conditioned place preference and locomotor sensitization induced by cocaine. Mice treated with saline or NMDA antagonist memantine (5 or 10 mg/kg) underwent repeated social defeat or were kept in the exploration control condition. After three weeks, all groups (SAL + RSD, M5 + RSD, M10 + RSD, SAL + EXP, M5 + EXP and M10 + EXP) were conditioned with 1 mg/kg of cocaine (experiment 1). After nine weeks, each group was subdivided into two groups: one received saline and the other cocaine (25 mg/kg) on 3 consecutive days. After a 5-day interval, all the animals received a challenge of cocaine (10 mg/kg) and their locomotor activity was registered (experiment 2). Only stressed animals developed place preference, an effect prevented by the low dose of memantine. Control defeated mice (but not those treated with memantine) showed greater activity than mice not exposed to stress. Our results show that glutamate NMDA receptors are involved in the higher vulnerability to cocaine effects provoked by exposure to social defeat. They also suggest that memantine could be a useful therapeutic tool for treatment of cocaine dependent individuals exposed to stress conditions.

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Exercise Training in Cancer Control and Treatment.

Exercise Training in Cancer Control and Treatment.

Compr Physiol. 2018 Dec 13;9(1):165-205

Authors: Christensen JF, Simonsen C, Hojman P

Abstract
Exercise training is playing an increasing role in cancer care, as accumulating evidence demonstrates that exercise may prevent cancer, control disease progression, interact with anti-cancer therapies, and improve physical functioning and psychosocial outcomes. In this overview article, we present the current state of the field of exercise oncology, which currently comprises of nearly 700 unique exercise intervention trials with more than 50,000 cancer patients. First, we summarize the range of these interventions with regard to diagnoses, clinical setting, timing, and type of intervention. Next, we provide a detailed discussion of the 292 trials, which have delivered structured exercise programs, outlining the impact of exercise training on cancer-specific, physiological, and psychosocial outcomes in the light of the challenges and physiological limitations cancer patients may experience. In summary, the safety and feasibility of exercise training is firmly established across the cancer continuum, and a wide range of beneficial effects on psychosocial and physiological outcomes are well documented. Many of these beneficial effects are linked to the general health-promoting properties of exercise. However, it is becoming increasing evident that exercise training can have direct effects on cancer and its treatment. This calls for future exercise oncology initiatives, which aim to target cancer-specific outcomes, and which are integrated into the concurrent cancer trajectory. Here, the field must bridge extensive knowledge of integrative exercise physiology with clinical oncology and cancer biology to provide a basis of individualized targeted approaches, which may place exercise training as an integrated component of standard cancer care. © 2019 American Physiological Society. Compr Physiol 9:165-205, 2019.

PMID: 30549018 [PubMed - in process]

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Projected clinical benefit of surveillance imaging for early detection and treatment of breast cancer metastases.

Projected clinical benefit of surveillance imaging for early detection and treatment of breast cancer metastases.

Breast J. 2018 Dec 12;:

Authors: O'Dell W, Takita C, Casey-Sawicki K, Daily K, Heldermon CD, Okunieff P

Abstract
This article presents current best knowledge to assess the projected outcomes benefit of adding multi-modality surveillance imaging to standard follow-up care for breast cancer patients at high risk (>30%) for developing future metastases. This analysis is motivated by recent preliminary clinical studies that have suggested that augmenting systemic treatment of early-stage metastases with targeted surgery and/or radiosurgery achieves significant overall survival and disease-free survival benefit. Our primary aims are to: (a) describe the clinical motivation and scan parameters needed to identify the early onset of metastatic progression in breast cancer patients for effective surgical or radiosurgical treatment; (b) estimate the anticipated survival benefit for high-risk patients under this recommended protocol; and (c) estimate the radiation risks associated with the repeated body imaging of this protocol.

PMID: 30548515 [PubMed - as supplied by publisher]

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Nilotinib in the treatment of chronic myeloid leukemia.

Nilotinib in the treatment of chronic myeloid leukemia.

Future Oncol. 2018 Dec 14;:

Authors: Sacha T, Saglio G

Abstract
Nilotinib, a second-generation tyrosine kinase inhibitor, was designed to overcome resistance of a wide range of BCR-ABL mutants to imatinib. When used in the first-line treatment in newly diagnosed  chronic myeloid leukemia (CML), it induces faster and deeper molecular responses in higher than imatinib percentage of patients. Treatment-free remission after achievement of sustained deep molecular response represents an emerging treatment goal for a proportion of patients with CML in chronic phase. The pharmacologic properties, and the role of nilotinib in the current treatment of CML in the context of considered optimal end point of therapy including the discontinuation trial and durable treatment-free remission achievement is discussed in the article.

PMID: 30547682 [PubMed - as supplied by publisher]

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Psychological symptoms and subsequent healthy lifestyle after a colorectal cancer diagnosis.

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Psychological symptoms and subsequent healthy lifestyle after a colorectal cancer diagnosis.

Health Psychol. 2018 03;37(3):207-217

Authors: Trudel-Fitzgerald C, Tworoger SS, Poole EM, Zhang X, Giovannucci EL, Meyerhardt JA, Kubzansky LD

Abstract
OBJECTIVE: Although medical professionals recommend lifestyle changes following a colorectal cancer (CRC) diagnosis to improve outcomes, such changes are not consistently implemented. This study examines whether higher distress is associated with lower likelihood of engaging in favorable behaviors after CRC diagnosis.
METHOD: Women from the Nurses' Health Study prospective cohort who completed anxiety (n = 145) and depression (n = 227) symptom scales within 4 years after receiving a CRC diagnosis were included. Measures of lifestyle (diet, physical activity, alcohol, smoking, body mass index [BMI]) were queried prediagnosis, when psychological symptoms were assessed (1988 and 1992, respectively), and then every 4 years thereafter until 2010. Women were categorized according to initial psychological symptoms levels and followed through 2010 or until last follow-up completed.
RESULTS: Higher versus lower anxiety symptoms were significantly related to unhealthier lifestyle scores throughout follow-up (β = -0.25, CI [-0.44, -0.05]); however, the rate of change over time was similar across groups (pinteraction effect = 0.41). Stratified analyses hinted that higher anxiety and depression symptoms were related to increased odds of reporting a future unhealthy lifestyle within 10-years postdiagnosis. Beyond 10 years, anxiety became statistically unrelated with future lifestyle, and higher depressive symptoms were associated with lower odds of subsequently having an unhealthy lifestyle, albeit nonstatistically significant (OR = 0.35, 95% CI [0.10, 1.24], p = 0.10).
CONCLUSIONS: Among women with CRC, higher anxiety and depression symptoms were associated with subsequent unhealthier lifestyle in the 10 years following diagnosis. With replication, such findings may suggest that treating psychological symptoms early in the cancer trajectory may not solely reduce psychological distress but also promote healthier lifestyle. (PsycINFO Database Record

PMID: 29154605 [PubMed - indexed for MEDLINE]

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Breast cancer genomics and immuno-oncological markers to guide immune therapies.

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Breast cancer genomics and immuno-oncological markers to guide immune therapies.

Semin Cancer Biol. 2018 10;52(Pt 2):178-188

Authors: Hammerl D, Smid M, Timmermans AM, Sleijfer S, Martens JWM, Debets R

Abstract
There is an increasing awareness of the importance of tumor - immune cell interactions to the evolution and therapy responses of breast cancer (BC). Not surprisingly, numerous studies are currently assessing the clinical value of immune modulation for BC patients. However, till now durable clinical responses are only rarely observed. It is important to realize that BC is a heterogeneous disease comprising several histological and molecular subtypes, which cannot be expected to be equally immunogenic and therefore not equally sensitive to single immune therapies. Here we review the characteristics of infiltrating leukocytes in healthy and malignant breast tissue, the prognostic and predictive values of immune cell subsets across different BC subtypes and the various existing immune evasive mechanisms. Furthermore, we describe the presence of certain groups of antigens as putative targets for treatment, evaluate the outcomes of current clinical immunotherapy trials, and finally, we propose a strategy to better implement immuno-oncological markers to guide future immune therapies in BC.

PMID: 29104025 [PubMed - indexed for MEDLINE]

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Targeting activator protein 1 signaling pathway by bioactive natural agents: Possible therapeutic strategy for cancer prevention and intervention.

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Targeting activator protein 1 signaling pathway by bioactive natural agents: Possible therapeutic strategy for cancer prevention and intervention.

Pharmacol Res. 2018 02;128:366-375

Authors: Tewari D, Nabavi SF, Nabavi SM, Sureda A, Farooqi AA, Atanasov AG, Vacca RA, Sethi G, Bishayee A

Abstract
Activator protein 1 (AP-1) is a key transcription factor in the control of several cellular processes responsible for cell survival proliferation and differentiation. Dysfunctional AP-1 expression and activity are involved in several severe diseases, especially inflammatory disorders and cancer. Therefore, targeting AP-1 has recently emerged as an attractive therapeutic strategy for cancer prevention and therapy. This review summarizes our current understanding of AP-1 biology and function as well as explores and discusses several natural bioactive compounds modulating AP-1-associated signaling pathways for cancer prevention and intervention. Current limitations, challenges, and future directions of research are also critically discussed.

PMID: 28951297 [PubMed - indexed for MEDLINE]

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Predictive value of preoperative statistical parametric mapping of regional glucose metabolism in mesial temporal lobe epilepsy with hippocampal sclerosis.

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Predictive value of preoperative statistical parametric mapping of regional glucose metabolism in mesial temporal lobe epilepsy with hippocampal sclerosis.

Epilepsy Behav. 2018 02;79:46-52

Authors: Kojan M, Doležalová I, Koriťáková E, Mareček R, Řehák Z, Hermanová M, Brázdil M, Rektor I

Abstract
OBJECTIVE: This study was designed to use statistical parametric mapping of interictal positron-emission tomography using [18F]Fluorodeoxyglucose (FDG-PET) to compare the brain metabolisms of patients with mesial temporal lobe epilepsy (MTLE)/hippocampal sclerosis and controls. Another aim of this study was to analyze the potential differences among patients in terms of epilepsy duration, side of hippocampal sclerosis, histopathological findings, insult in their history, and postoperative outcomes.
METHODS: We analyzed FDG-PET scans from 49 patients with MTLE/hippocampal sclerosis and 24 control subjects. We analyzed the differences in regional glucose metabolism between the patients and the control group and within the patient group using multiple variables.
RESULTS: We observed widespread hypometabolism in the patient group in comparison with the control group in temporal and extratemporal areas on the epileptogenic side (ES). On the nonepileptogenic side (NES), we observed the most hypometabolism in the thalamus and the anterior and middle cingulate gyrus. In the group of patients with more severe hippocampal sclerosis, we observed statistically significant hypometabolism in the insula on the ES. In patients with poor postoperative outcomes, we found statistically significant hypometabolism in the insula on the ES and the temporal pole (TP) on the NES. Patients with any insult in their history showed hypermetabolism in the TP on both sides.
CONCLUSION: Our study showed that there are widespread changes in metabolism in patients with MTLE in comparison to controls, either inside or outside the temporal lobe. There are significant differences among these patients in terms of postoperative outcomes, degree of hippocampal sclerosis, and insults in their history.

PMID: 29247965 [PubMed - indexed for MEDLINE]

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The Temple Star Transitional Model of Care for epilepsy; the outcome of a quality improvement project.

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The Temple Star Transitional Model of Care for epilepsy; the outcome of a quality improvement project.

Epilepsy Behav. 2018 02;79:4-8

Authors: Crowley SL, Byrne S, McNulty S, Keating K, Nestor T, Owen Y, O'Rourke D, Lynch B, Shahwan A, King MD

Abstract
OBJECTIVE: The aim and objective of this study was to assess the knowledge and views of parents on transitional and adolescent care in young adults with epilepsy, and to develop a transitional and adolescent program for epilepsy.
METHODS: Data were collected from questionnaires completed by parents during focus groups exploring transitional care and inherent issues for young adults, aged 12-18years, with epilepsy. The questionnaire assessed the current knowledge and views of parents of children with epilepsy on transitional care, and following a presentation on "Transition in Epilepsy" (including themes such as self-advocacy, independent healthcare behavior, sexual health, psychosocial support, educational and vocational planning, health and lifestyle issues) assessed feedback on the proposed model of care in transitional and adolescent care.
RESULTS: Data were collected from 34 parents; the majority of parents, 74% (n=25), wish their children to be transitioned and transferred over to the adult epilepsy sites at the age of 18years. Over 82% (n=28) of parents believe the concept of transition should be introduced between the ages of 12-16years.
CONCLUSION: This quality improvement initiative identified the need for transitional care to begin at an early age. This study engaged parents in a process to improve adolescent and transitional care for adolescents with epilepsy. This study also highlights the importance of introducing a detailed preparatory phase for a transitional and adolescent care in epilepsy.

PMID: 29223006 [PubMed - indexed for MEDLINE]

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ECoG high-gamma modulation versus electrical stimulation for presurgical language mapping.

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ECoG high-gamma modulation versus electrical stimulation for presurgical language mapping.

Epilepsy Behav. 2018 02;79:26-33

Authors: Arya R, Horn PS, Crone NE

Abstract
OBJECTIVE: This meta-analysis compared diagnostic validity of electrocorticographic (ECoG) high-γ modulation (HGM) with electrical stimulation mapping (ESM) for presurgical language localization.
METHODS: From a structured literature search, studies with electrode level data comparing ECoG HGM and ESM for language localization were included in the meta-analysis. Outcomes included global measures of diagnostic validity: area under the summary receiver operating characteristic (SROC) curve (AUC), and diagnostic odds ratio (DOR); as well as pooled estimates of sensitivity and specificity. Clinical and technical determinants of sensitivity/specificity were explored.
RESULTS: Fifteen studies were included in qualitative synthesis, and 10 studies included in the meta-analysis (number of patients 1-17, mean age 10.3-53.6years). Overt picture naming was the most commonly used task for language mapping with either method. Electrocorticographic high-γ modulation was analyzed at 50-400Hz with different bandwidths in individual studies. For ESM, pulse duration, train duration, and maximum current varied greatly among studies. Sensitivity (0.23-0.99), specificity (0.48-0.96), and DOR (1.45-376.28) varied widely across studies. The pooled estimates are: sensitivity 0.61 (95% CI 0.44, 0.76), specificity 0.79 (95% CI 0.68, 0.88), and DOR 6.44 (95% CI 3.47, 11.94). Area under the SROC curve was 0.77. Results of bivariate meta-regression were limited by small samples for individual variables.
CONCLUSION: Electrocorticographic high-γ modulation is a specific but not sensitive method for language localization compared with gold-standard ESM. Given the pooled DOR of 6.44 and AUC of 0.77, ECoG HGM can fairly reliably ascertain electrodes overlying ESM cortical language sites.

PMID: 29247963 [PubMed - indexed for MEDLINE]

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Magnetoencephalographic Recordings in Infants: A Retrospective Analysis of Seizure-Focus Yield and Postsurgical Outcomes.

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Magnetoencephalographic Recordings in Infants: A Retrospective Analysis of Seizure-Focus Yield and Postsurgical Outcomes.

J Clin Neurophysiol. 2018 Nov;35(6):454-462

Authors: Garcia-Tarodo S, Funke M, Caballero L, Zhu L, Shah MN, Von Allmen GK

Abstract
PURPOSE: Magnetoencephalography (MEG) is often incorporated into the presurgical work-up of children with pharmacoresistant epilepsy. There is growing literature on its role in improving selection for epilepsy surgery, particularly when brain MRI is "non-lesional" or in patients with recurrence or intractable seizures after epilepsy surgery. There are, however, no reports on the extrapolation of its role in the presurgical decision-making process of infants.
METHODS: We performed a retrospective analysis of infants who underwent MEG over a 10-year period at our center for presurgical work-up. We reviewed medical records to ascertain seizure history, work-up procedures including brain MRI and scalp EEG, and in the case of surgery, intracranial recordings, operative notes, and follow-up outcomes.
RESULTS: We identified 31 infants (<2 years of age) who underwent MEG recordings. Despite EEG interictal readings showing patterns of generalized dysfunction in 80%, MEG was able to pinpoint the foci of epileptic activity in 45%. In the MRI-negative group, 44% had focal lateralized interictal spikes on MEG. The sensitivity of MEG to detect interictal epileptiform activity was 90%, and its ability to provide additional information was 28%. Among 18 infants who had surgery, 13 became seizure free at follow-up. The percentage of infants with a focal spike volume on MEG studies and a seizure-free outcome was 66%.
CONCLUSIONS: MEG recordings in infants were found to be as sensitive for identifying seizure focus as other age groups, also supplying additional information to the decision-making process and validating its role in the presurgical work-up of infants with intractable epilepsy.

PMID: 30004913 [PubMed - indexed for MEDLINE]

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The clinical impact of integration of magnetoencephalography in the presurgical workup for refractory nonlesional epilepsy.

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The clinical impact of integration of magnetoencephalography in the presurgical workup for refractory nonlesional epilepsy.

Epilepsy Behav. 2018 02;79:34-41

Authors: Mohamed IS, Bouthillier A, Bérubé A, Cossette P, Finet P, Saint-Hilaire JM, Robert M, Nguyen DK

Abstract
OBJECTIVE: For patients with nonlesional refractory focal epilepsy (NLRFE), localization of the epileptogenic zone is more arduous, and intracranial electroencephalography (EEG) (icEEG) is frequently required. Planning for icEEG is dependent on combined data from multiple noninvasive modalities. We report the negative impact of lack of integration of magnetoencephalography (MEG) in the presurgical workup in NLRFE.
METHODS: Observational MEG case series involving 31 consecutive patients with NLRFE in an academic epilepsy center. For various reasons, MEG data were not analyzed in a timely manner to be included in the decision-making process. The presumed impact of MEG was assessed retrospectively.
RESULTS: Magnetoencephalography would have changed the initial management in 21/31 (68%) had MEG results been available by reducing the number of intracranial electrodes, modifying their position, allowing for direct surgery, canceling the intracranial study, or providing enough evidence to justify one. Good surgical outcome was achieved in 11 out of 17 patients who proceeded to epilepsy surgery. Nine out of eleven had MEG clusters corresponding to the resection area, and MEG findings would have allowed for direct surgery (avoiding icEEG) in 2/11. Six patients had poor outcome including three patients where MEG would have significantly changed the outcome by modifying the resection margin. Magnetoencephalography provided superior information in 3 patients where inadequate coverage precluded accurate mapping of the epileptogenic zone.
CONCLUSION: In this single center retrospective study, MEG would have changed patient management, icEEG planning, and surgical outcome in a significant percentage of patients with NLRFE and should be considered in the presurgical workup in those patients.

PMID: 29253675 [PubMed - indexed for MEDLINE]

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The T-type calcium channel antagonist, Z944, alters social behavior in Genetic Absence Epilepsy Rats from Strasbourg.

The T-type calcium channel antagonist, Z944, alters social behavior in Genetic Absence Epilepsy Rats from Strasbourg.

Behav Brain Res. 2018 Dec 11;:

Authors: Marks WN, Zabder NK, Cain SM, Snutch TP, Howland JG

Abstract
Abnormalities in social behavior are a co-morbid symptom of idiopathic generalized epilepsies such as childhood absence epilepsy. The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) model is a spontaneously occurring absence epilepsy phenotype closely correlated to that of human absence epilepsies. Similar to the human conditions, GAERS display social abnormalities. Previous studies have only demonstrated social abnormalities in female GAERS, whereas social problems are observed in male and female patients. Seizures in GAERS result in part due to a gain-of-function missense mutation in the Cav3.2 T-type calcium channel gene. This study examined the effects of the pan-T-type calcium channel antagonist, Z944, on social interaction behaviors in male and female GAERS using an open field social interaction test. A second objective of this study was to examine the effects of Z944 on anxiety-like behavior in an open field locomotion test and elevated plus maze. Results showed a decrease in social activity in GAERS relative to non-epileptic control (NEC) rats. Acute, systemic Z944 (5 mg/kg; i.p.) consistently reduced introductory and aggressive behaviors in both GAERS and NECs, whereas, strain effects were observed for over-and-under crawl behaviors. In the open field locomotion test and elevated plus maze, Z944 increased anxiety-like behaviors in GAERS, whereas, Z944 produced inconsistent effects on anxiety-like behaviors in NECs. The results of this study suggest that the regulation of T-type calcium channel activity may be a useful strategy for the development of new therapeutic approaches for the treatment of social and affective abnormalities observed in absence epilepsy disorders.

PMID: 30550952 [PubMed - as supplied by publisher]

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Autostimulation in Vagus Nerve Stimulator Treatment: Modulating Neuromodulation.

Autostimulation in Vagus Nerve Stimulator Treatment: Modulating Neuromodulation.

Neuromodulation. 2018 Dec 14;:

Authors: Kulju T, Haapasalo J, Rainesalo S, Lehtimäki K, Peltola J

Abstract
OBJECTIVES: Until now, the vagus nerve stimulation (VNS) treatment in epilepsy has consisted of two different modes: normal and magnet stimulation. A new vagus nerve stimulator model (106 AspireSR®, LivaNova, Houston, TX, USA) also allows automatic stimulation (AutoStim). The purpose of this study is to examine the effect of autostimulation on seizure frequencies together with energy consumption.
MATERIALS AND METHODS: The study material consisted of 14 patients whose former stimulator model (102/103) was replaced with model 106. We calculated the theoretical charge (Q) in Coulombs for one day in both of those groups. We evaluated the follow-up data of the patients' seizure counts, with a mean follow-up time of 18.1 months (SD 8.1).
RESULTS: The total charge, "VNS dose," was reduced with model 106 in comparison with models 102 or 103 (p = 0.001, Mann-Whitney test). The average charge (Qtotal ) for one day with AutoStim was 142.56 mC; without AutoStim, it was 321.09 mC. We were able to assess seizure diaries in 11 out of 14 patients. Four patients (36%) had >50% seizure reduction and two patients (18%) experienced a reduction in seizure severity with VNS with autostimulation. Five patients (46%) remained unchanged. In three out of four patients with improved seizure control, the duty cycle was maintained at the original level. The patients whose duty cycle was modified for a more prolonged OFF-time had unchanged seizure frequencies.
CONCLUSION: VNS with AutoStim achieves maintenance of prior-established seizure control with markedly less energy consumption and can also improve seizure control as compared to former stimulator model.

PMID: 30549376 [PubMed - as supplied by publisher]

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The electroclinical spectrum, etiologies, treatment and outcome of nonconvulsive status epilepticus in the elderly.

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The electroclinical spectrum, etiologies, treatment and outcome of nonconvulsive status epilepticus in the elderly.

Epilepsy Behav. 2018 02;79:53-57

Authors: Canas N, Delgado H, Silva V, Pinto AR, Sousa S, Simões R, Inácio N, Vale J

Abstract
BACKGROUND: Nonconvulsive status epilepticus (NCSE) in the elderly is particularly difficult to diagnose, mainly due to subtle clinical manifestations and associated comorbidities. The recently validated electroencephalography (EEG) diagnostic criteria for NCSE and the proposed operational classification of status epilepticus provide tools that can allow an earlier diagnosis and better management of NCSE in this age group, possibly contributing to reduce its high mortality.
MATERIAL AND METHODS: we used these tools to identify and characterize a cohort of elderly (>60year-old) patients admitted at our institution in a 3-year period; the video-EEG and clinical files of the patients fulfilling EEG diagnostic criteria for NCSE were reviewed, being in this study described their electroclinical spectrum, etiologies, treatment, inhospital mortality, and status epilepticus severity score (STESS).
RESULTS: Fourty patients (23 women; mean age 76.6years) were identified. Although dyscognitive NCSE associated with >2.5Hz of epileptiform discharges (ED) was the most frequent electroclinical phenotype, this was quite heterogeneous, ranging from patients with aura continua to patients in coma, associated with frequent ED or rhythmic slow activities. Acute symptomatic (45%) and multifactorial (27.5%) etiologies were the most common, and associated with the worst prognosis. There was a trend to use newer antiepileptic drugs in the early steps of NCSE treatment. The inhospital mortality was high (22.5%) and predicted by STESS scores ≥3.
CONCLUSION: In the elderly, NCSE has heterogeneous electroclinical phenotypes and etiologies. In spite of the treatment limitations conditioned by the comorbidities, more aggressive treatments could be justified to reduce mortality in patients with high STESS scores.

PMID: 29253676 [PubMed - indexed for MEDLINE]

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Combination of free-breathing radial 3D fat-suppressed T1-weighted gradient-echo sequence with diffusion weighted images: Potential for differentiating malignant from benign peripheral solid pulmonary masses

Publication date: Available online 14 December 2018

Source: Magnetic Resonance Imaging

Author(s): Shan Dang, Xiang Gao, Guangming Ma, Nan Yu, Dong Han, Qi Yang, Xin Tian, Haifeng Duan

Abstract

Objectives

High resolution CT is the most commonly used radiological method for differentiating benign from malignant peripheral solid pulmonary masses, however, some of them are not easily diagnosed by morphology alone. Furthermore, due to the radiation dose, it is unsuitable for patients with disorders requiring repeated examinations over prolonged periods. The aims of this study were to evaluate whether a combination of diffusion-weighted images (DWI) and free-breathing radial 3D fat-suppressed T1-weighted gradient echo (radial volumetric interpolated breath-hold examination, radial VIBE) sequence can enable discrimination between benign from malignant peripheral solid pulmonary masses.

Materials and methods

Both chest CT scan and MR imaging with radial VIBE and DWI were obtained from 47 patients; 30 males and 17 females (mean age 64 years old; age range 48–83 years old). Benign and malignant peripheral solid pulmonary masses were conclusively identified by pathology results. Two radiologists independently reviewed all the images and record radiological features including morphological signs on radial VIBE, CT images, and ADC value. Receiver operating characteristic (ROC) was used to analyze the capability of radial VIBE as well as DWI to distinguish malignant from benign peripheral solid pulmonary masses.

Results

In 77% of patients, malignant peripheral solid pulmonary masses were found. Morphological signs of mediastinal lymph node enlargement and lobulation were more easily found in malignant masses in both radial VIBE (mediastinal lymph node enlargement: p = 0.033, lobulation: p = 0.039) and CT (mediastinal lymph node enlargement: p = 0.004, lobulation: p = 0.012). The ADC value were also significant difference between benign and malignant groups (p = 0.001). Combined ADC value with radial VIBE was a most specific test than routine-dose CT (86.1% vs 75%, p < 0.001), but less sensitive than routine-dose CT (81.8% vs 90.9%; p < 0.001) for malignant peripheral solid pulmonary masses detection. Diagnostic accuracy was 89% for combining ADC value with radial VIBE, and 85% for routine-dose CT.

Conclusions

Combination of morphological signs and ADC value seems to improve differentiating malignant from benign peripheral solid pulmonary masses. Especially in patients unable to endure radiation exposure, suspend respiration, radial VIBE provides similar morphological signs displaying to those on routine-dose CT.

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A new class of diamide scaffold: Design, synthesis and biological evaluation as potent antimitotic agents, tubulin polymerization inhibition and apoptosis inducing activity studies.

A new class of diamide scaffold: Design, synthesis and biological evaluation as potent antimitotic agents, tubulin polymerization inhibition and apoptosis inducing activity studies.

Bioorg Chem. 2018 Dec 05;84:399-409

Authors: Mohamed KO, Zaki I, El-Deen IM, Abdelhameid MK

Abstract
A new series of diamide functional compounds has been designed, synthesized and confirmed by spectroscopic methods and elemental analyses. All the synthesized compounds were evaluated for their antiproliferative activity on HepG2 cell line. Compounds 3k and 3l were proved to have potent anticancer activity equipotent or more potent than reference compound Combretastatin A-4. The results of DNA flow cytometry analysis demonstrated cell cycle arrest at G2/M phase. The extent of apoptosis induced by 3k and 3l was also determined. Moreover, the compounds produced a significant reduction in cellular microtubules for microtubule loss and potently inhibited the binding of [3H]colchicine to tubulin. Compounds 3k and 3l were proved to upregulate expression of proteins triggering apoptosis, such as p53, Bax, and decreased Bcl-2 overexpression as well as increased the expression of effector caspase- 3/7.

PMID: 30551066 [PubMed - as supplied by publisher]

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[Progress in the study of artemisinin and its derivatives against head and neck cancer].

[Progress in the study of artemisinin and its derivatives against head and neck cancer].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2018 Oct 05;32(19):1519-1523

Authors: Liang YZ, Nong XL

Abstract
The head and neck cancer is one of the most common malignant tumors in the world. There are more than 600 000 new cases in the world every year. Cisplatin is often used in the treatment of head and neck cancer at present. However, because of its side effects and drug resistance, cisplatin often failed in the treatment of head and neck cancer. Artemisinin and its derivatives as first-line antimalarial drugs have the advantages of high efficiency, low toxicity and so on. Further study found that artemisinin and its derivatives had cytotoxic effects against head and neck cancer through inducing cell cycle arrest, inducing tumor cell apoptosis and inhibiting cell invasion and migration, oxidative damage, blocking the cell signal transduction and inhibiting angiogenesis. Studying the anti-tumor effects of artemisinin and its derivatives allows for development of safer and more effective antitumor drugs and pain-reduction caused by diseases and traditional treatment, then improve the survival rate and life quality of patients with head and neck cancer. This article reviews the progress in the study of artemisinin and its derivatives in the treatment of head and neck cancer.

PMID: 30550204 [PubMed]

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Asperyellone prevents HDF cells from UVB irradiation damages: An elaborated study.

Asperyellone prevents HDF cells from UVB irradiation damages: An elaborated study.

J Cell Biochem. 2018 Dec 12;:

Authors: Santhakumaran I, Shanuja SK, Narayanaswamy R, Gnanamani A

Abstract
The current study explores the photo-protective effect of asperyellone (AY) (a fungal secondary metabolite), assessed under in vitro condition using human dermal fibroblast cell line. AY was isolated from Aspergillus sp. during the resting phase and purified. The initial cytocompatibility assessment on concentrations of AY and the duration of exposure of UVB irradiations were studied respectively. N-acetyl-L-cysteine (NAC) was used as positive control. Cells were then pretreated with optimized concentration of AY (2.0 μM) and NAC (1 mM) for 1 hour and then UVB irradiated (30 mJ/cm 2 ) for the period of 10 minutes. Results revealed that reactive oxygen species generated upon UVB irradiation found scavenged by the AY pretreatment at a significant level. Furthermore, an appreciable reduction in apoptotic cell count and DNA damages support the scavenging effect of AY. Assessments on the expression of enzymatic and nonenzymatic antioxidants evidently prove the protective role of AY. The reduced expression levels of inflammatory markers (TNF-α and COX-2), collagen degraders (MMP 2 and MMP 9), apoptotic protein expressions (Bax and Bcl-2), and cell-cycle arrest analyses substantiate the photo-protective effect of AY similar to NAC (positive control). Thus, the observations made in the current study indicate the possible role of AY as a photo-protective agent.

PMID: 30548661 [PubMed - as supplied by publisher]

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LINC01133 aggravates the progression of hepatocellular carcinoma by activating the PI3K/AKT pathway.

LINC01133 aggravates the progression of hepatocellular carcinoma by activating the PI3K/AKT pathway.

J Cell Biochem. 2018 Dec 11;:

Authors: Zheng YF, Zhang XY, Bu YZ

Abstract
LncRNAs exhibit crucial roles in various pathological diseases, including hepatocellular carcinoma (HCC). Therefore, it is significant to recognize the dysregulated lncRNAs in HCC progression. Recently, LINC01133 has been identified in several tumors. However, the biological role of LINC01133 in HCC remains poorly understood. Currently, we focused on the function of LINC01133 in HCC development. We observed that LINC01133 was significantly increased in HCC cells including HepG2, Hep3B, MHCC-97L, SK-Hep-1, and MHCC-97H cells compared with the normal human liver cell line HL-7702. In addition, PI3K/AKT signaling was highly activated in HCC cells. Knockdown of LINC01133 was able to inhibit HCC cell proliferation, cell colony formation, cell apoptosis, and blocked cell cycle arrest in the G1 phase. For another, downregulation of LINC01133 repressed HCC cell migration and invasion. Subsequently, the PI3K/AKT signaling pathway was strongly suppressed by silence of LINC01133 in Hep3B and HepG2 cells. Then, in vivo tumor xenografts models were established using Hep3B cells to explore the function of LINC01133 in HCC progression. Consistently, our study indicated that knockdown of LINC01133 dramatically repressed HCC tumor progression through targeting the PI3K/AKT pathway in vivo. Taken these together, we revealed that LINC01133 contributed to HCC progression by activating the PI3K/AKT pathway.

PMID: 30548306 [PubMed - as supplied by publisher]

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Morin inhibits PDGF-induced proliferation, migration, and invasion of vascular smooth muscle cells via modulating p27KIP1, AKT, and MMP-9 activities.

Morin inhibits PDGF-induced proliferation, migration, and invasion of vascular smooth muscle cells via modulating p27KIP1, AKT, and MMP-9 activities.

Gen Physiol Biophys. 2018 Sep;37(6):633-645

Authors: Shin SS, Ko MC, Noh DH, Hwang B, Park Y, Park SL, Kim WJ, Moon SK

Abstract
Hyper-proliferation and migration of vascular smooth muscle cells (VSMCs) are closely associated with atherosclerosis. Recently, the flavonol morin has been reported to exhibit potent anti-oxidant and anti-inflammatory activities. Therefore, we investigated molecular mechanisms of morin in VSMCs stimulated by PDGF. Morin effectively inhibited PDGF-stimulated proliferation of VSMCs through a G1 cell-cycle arrest, leading to down-regulation of CDK2, CDK4, cyclin D1, and cyclin E proteins. Interestingly, PDGF markedly down-regulated p27KIP1 protein expression; however, morin treatment restored the p27KIP1expression to the basal level. Morin did not affect phosphorylation of MAPKs (ERK, p38, and JNK); however, phosphorylation of AKT was dramatically suppressed by morin in PDGF-stimulated VSMCs. Using the PI3K inhibitor, LY294002, we revealed that AKT is a key regulator in the inhibitory mechanism of morin against PDGF-induced proliferation of VSMCs. Morin disturbed migratory and invasive potential of VSMCs via suppression of matrix metalloproteinase-9 (MMP-9) activity. Using electrophoretic mobility shift assays, we verified that NF-κB, AP-1, and Sp-1 transcription factors are implicated in the mode of action of morin, which suppresses the MMP-9 activity in PDGF-induced VSMCs. Based on the results, we believe that morin may be a potential therapeutic agent for atherosclerosis without negative side effect.

PMID: 30547894 [PubMed - in process]

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The diagnostic and antibiotics reference values of procalcitonin for intracranial infection after craniotomy.

The diagnostic and antibiotics reference values of procalcitonin for intracranial infection after craniotomy.

World Neurosurg. 2018 Dec 11;:

Authors: Zhu L, Dong L, Li Y, Zhang H, Wang X, Liu X, Teng Z, Xia B, Zhang P

Abstract
OBJECTIVE: To evaluate the values of CSF and serum PCT for the diagnosis of intracranial infection after craniotomy and the relationship between them, and explore the PCT value about the application in the clinical antibiotics guidance.
METHODS: Reviewing the incidence of intracranial infection in 21 craniotomy patients from the Subei People Hospital of Northern Jiangsu Province. CSF samples and venous blood were collected for the analysis. Diagnostic parameters were calculated via the ROC curves, and inflammatory indicators were analyzed before and after the application of antibiotics in the infection group.32 non-infection patients were recruited for the same measurements as control.
RESULTS: CSF and serum PCT levels in the infection group were higher than that in non-infection group (P values<0.05), and the diagnostic efficiency of CSF PCT(AUC=0.86, DOR=41.40) was superior than serum PCT (AUC=0.66, DOR=3.40). The diagnostic efficiency was more powerful when serial test was used (specificity=0.99, PLR=37.10, DOR=54.45). All the inflammatory indicators decreased after the application of antibiotics except the CSF protein (P=0.129), and no obvious correlation was seen between CSF and serum PCT. Dynamic change of PCT can be used as a reference for adjusting antibiotics. CSF PCT can also be used as an indicator to identify intracranial gram-negative bacteria infection.
CONCLUSIONS: CSF PCT is a good marker for intracranial infection. It could be used as a method to help confirm intracranial infection and provide guidance for the clinical antibiotics when combined with serum PCT.

PMID: 30550873 [PubMed - as supplied by publisher]

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Residential Mobility and Flourishing Among United States School-Age Children, 2011/2012 National Survey of Children’s Health

Abstract

Objectives To investigate the association of residential mobility with flourishing among school-age children. Methods Data from the 2011/2012 National Survey of Children's Health were used to examine parent/caregiver-reported information on flourishing and residential mobility for children age 6–17 (N = 63,333). Residential mobility was the number of times the child moved categorized as: none, 1–2, and 3+. Children who were reported to show interest/curiosity, finish tasks, stay calm/in control, care about doing well in school, and do all homework were coded as flourishing. Sex-specific multivariable models were used to model the relative risk of mobility on flourishing. Interactions of mobility with age and poverty were tested. Results Among US school-age children, 22% had no moves, 39% had 1–2 moves and 39% had 3+ moves in their lifetime. Nearly half (45%) were flourishing. Both boys and girls who moved 3+ times were less likely to flourish compared to children with no moves. Among poor boys moving 3+ times was associated with less flourishing (aRR 0.83, 95% CI 0.71, 0.98) with no association for non-poor boy. Among girls the pattern was reversed (aRR 0.88, 95% CI 0.81, 0.95 for non-poor girls and no association for poor girls). Conclusions for Practice Residential mobility may lead to lower rates of flourishing. The patterns, when stratified by age or poverty, are different for boys and girls.

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Relief of intractable pruritus with romidepsin in patients with cutaneous T‐cell lymphoma: a series of 4 cases

ABSTRACT

Cutaneous T‐cell lymphomas (CTCL) are a relatively rare and heterogeneous group of non‐Hodgkin lymphomas that typically present in the skin. The majority of patients with CTCL experience pruritus, which can interfere with daily activities, significantly impact quality of life, and is typically uncontrolled by standard anti‐itch therapies. Several lymphoma treatments have reported anti‐pruritic effects including romidepsin, a potent class 1 selective histone deacetylase inhibitor approved for the treatment of patients with CTCL who have had at least 1 prior systemic therapy. Here, we describe the cases of 4 patients with debilitating and refractory pruritus that were resolved with romidepsin. Resolution of pruritus was observed in both clinical responders and non‐responders, and dose modification was used successfully to manage adverse events and for maintenance treatment. The potential for pruritus relief with romidepsin should be considered when treating patients with CTCL.

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Vitamin D Supplements Don’t Reduce Cancer Incidence

Vitamin D Supplements Don't Reduce Cancer Incidence, Trial Shows
12/13/2018
	In the largest-ever randomized trial testing vitamin D for cancer prevention, the supplement did not lower the risk of developing cancer. The Vitamin D and Omega-3 Trial (VITAL) includes a nationally representative sample of nearly 26,000 participants.

Illumina MiSeq Sequencing Investigation of Microbiota in Bronchoalveolar Lavage Fluid and Cecum of the Swine Infected with PRRSV

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant animal morbidity and mortality and economic losses worldwide. In this study, we analyzed the microbiota in bronchoalveolar lavage fluid (BAL), mucosa, and feces in cecum of the PRRSV-challenged pigs using the Illumina MiSeq sequencing platform, to investigate the role of microbiota in the pathogenesis and development of porcine reproductive and respiratory syndrome (PRRS). Quantitative insights into microbial ecology analyses indicated that the dominant bacterial groups in the lung from the PRRSV-challenged pigs were Haemophilus parasuis and Mycoplasma hyorhinis, with a relative abundance of 35–48% and 27–41%, respectively. Our results were consistent with the clinical observation that the PRRSV-infected pigs are always co-infected with other bacteria, such as Haemophilus and Mycoplasma. On the other hand, Campylobacter and Clostridium became the two most abundant bacteria in the mucosal and luminal microbiota of the cecum of the PRRSV-challenged pigs, and the relative abundance was four times higher than that in the healthy pigs. This suggested that Campylobacter and Clostridium might be associated with the pathogenesis of diarrhea in PRRS. Linear discriminant analysis effect size reveals significant microbial dysbiosis of BAL, mucosa, and feces in cecum of the PRRSV-challenged pigs. We have identified a structural imbalance of the microbiota, characterized by a reduced diversity of microbiota and abundance alterations of certain bacteria in the PRRSV-challenged pigs. The observed microbiota dysbiosis in this study provides insight into the roles of the microbiota in the complications of the PRRSV infection.

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Indian Journal of Nephrology (Indian J Nephrol)

ORIGINAL ARTICLES
	Epidemiology and outcomes of acute kidney injury in critically ill: Experience from a tertiary care center	p. 413
	PS Priyamvada, R Jayasurya, Vijay Shankar, S Parameswaran DOI:10.4103/ijn.IJN_191_17   There is only limited information on the epidemiology and outcomes of acute kidney injury (AKI) in critically ill patients from low- and middle-income countries. This study aims to identify the etiology, short-term outcomes, and determinants of mortality in patients with AKI admitted to multiple medical and surgical Intensive Care Units (ICU's) in a tertiary care center. The study also aims to compare the clinical characteristics and outcomes of community-acquired AKI (CAAKI) and hospital-acquired AKI (HAAKI). A prospective, observational study was done from June 2013 to October 2015. All patients over 18 years with AKI admitted in various medical and surgical ICU's seeking nephrology referral were included. AKI was defined according to KDIGO criteria. The follow-up period was 30 days. A total of 236 patients were recruited from five medical and nine surgical ICU's. Majority (73.3%) were males. About 53.38% patients had CAAKI, whereas 46.61% had HAAKI. The predominant etiologies for AKI were sepsis (22.4%), trauma due to road traffic accidents (21.18%), acute abdomen (perforation, acute pancreatitis, bowel gangrene, intestinal obstruction and cholangitis) (18.64%), and cardiac diseases (10.59%). Sepsis and acute abdomen were the most common causes of CAAKI, whereas trauma and cardiac causes were the predominant causes of HAAKI (P < 0.05). Patients with HAAKI were younger, admitted in surgical units, had lower SOFA scores, lower serum creatinine, lesser need for dialysis, longer hospital stay, and earlier stages of AKI compared to patients with CAAKI (P < 0.05). The 30-day mortality was 52.54%. The mortality was not different between CAAKI and HAAKI (56.3% vs. 48.18%; relative risk = 0.86: 95% confidence interval 0.67–1.1). The mortality was similar across different stages of AKI.
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	Skin microcirculatory changes in relation to arteriovenous fistula maturation	p. 421
	Siew Cheng Chai, Wan Azman Wan Sulaiman, Arman Zaharil Mat Saad, Aida Hanum Rasool, Amran Ahmed Shokri DOI:10.4103/ijn.IJN_402_17   Maturation of arteriovenous fistula (AVF) involves complex vascular remodeling. In this study, we evaluated the changes of skin microvascular perfusion over the extremity with AVF maturation using the laser Doppler fluximetry (LDF). A total of 45 patients with chronic kidney disease, Stages IV–V, were included; they had undergone AVF creation from July 2014 to June 2016 at our institute. The measurement of skin microvascular perfusion was accomplished proximal and distal to the fistula anastomosis site: pre- and post-operative day 1, week 2, week 6, and week 12. Thirty-two patients with mean age of 55.6 had achieved AVF maturation. There were 40.6% radial-based and 59.4% brachial-based AVF. There was a 32.8% reduction of mean skin perfusion distal to the fistula by day 1 compared to the baseline perfusion; however, perfusion increased 47% by week 2 compared to day 1 and no dramatic change was subsequently noted. There was an increase of mean skin perfusion, proximal to fistula anastomosis, over 12 weeks with 35.8% at day 1 from the baseline. However, the changes of the mean skin perfusion were not statistically significant. There was no significant relation of skin perfusion changes with the type of fistula, diabetes mellitus, hypertension, and hyperlipidemia. LDF successfully detected the subclinical change of skin microvascular perfusion in relation to AVF creation. Reduction of skin perfusion distal to the fistula suggests that in patients with existing perfusion inadequacy of extremities, they may experience ischemic symptoms as early as day 1 postoperation, and require close monitoring for distal limb ischemic-related complications.
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	Urinary neutrophil gelatinase-associated lipocalin and urinary soluble CXCL16 as biomarkers of activity in pediatric lupus nephritis	p. 427
	MA El-Gamasy, W El-Naghy DOI:10.4103/ijn.IJN_265_17   One of the challenges of treating patients with lupus nephritis (LN) is to assess disease activity. The aim of this study was to measure the urinary neutrophil gelatinase-associated lipocalin (uNGAL) and urinary soluble chemokine (C-X-C motif) ligand 16 (CXCL16) levels in children and adolescents with systemic lupus erythematosus (SLE) and investigate whether they are elevated in active LN. This study was conducted on 80 patients diagnosed as SLE by the Systemic Lupus International Collaborating Clinics criteria and 60 apparently healthy individuals as controls. Global and renal disease activities were evaluated by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and renal SLEDAI, respectively. uNGAL and urinary CXCL16 were measured for all participants by ELISA. Renal biopsy was done for all cases at initial diagnosis and was graded using ISN/RPS classification. uNGAL and CXCL16 were higher in patients than in the controls (8.9 ± 3.56 ng/dl and 1067 ± 367 ug/L vs. 2.26 ± 1.95 ng/dl and 471 ± 106 ug/L, respectively). uNGAL had higher sensitivity and specificity than urinary CXCL16 as predictor of LN (95% and 90% vs. 85% and 80%, respectively). There was significant positive correlations between uNGAL levels, 24-h urinary proteins (r = 0.732, P = 0.001), and SLEDAI (r = 0.359, P = 0.001). There was also significant positive correlations between urinary CXCL16 levels, 24-h urinary proteins (r = 0.47, P = 0.001), and SLEDAI (r = 0.17, P = 0.001). uNGAL and CXCL16 were reliable indicators of the activity of LN.
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	Optimization of treatment modality in elderly end-stage renal disease population: Peritoneal dialysis versus transplant	p. 433
	A Kaul, MR Behera, R Kishore, B Karthikeyan, DS Bhadauria, P Mishra, N Prasad, A Gupta, RK Sharma DOI:10.4103/ijn.IJN_305_17   Despite kidney transplantation (KT) being considered as the best treatment modality for end-stage renal disease (ESRD), patient and graft survival in the elderly population is poorer than younger individuals. Many authors argue that prolonged life expectancy outweighs the risk of remaining on dialysis, but few studies had compared the treatment modalities, especially with peritoneal dialysis (PD). A retrospective study was conducted at a tertiary care institute to compare outcome of elderly ESRD patients, who received KT with those continued on PD; and to evaluate the predictors of patient survival. Patient survival at 1 year was (76.2% vs. 91.1%); 5 years (53.7% vs. 21.8%); and 10 years (35.6% vs. 0.00%) among KT and PD population, respectively. Infection was the most common cause of death among KT group (35 [41.2%] vs. 34 [28.2%]) while cardiovascular mortality in PD group (55 [46.2%] vs. 7 [8.2%]). Technique survival at 1, 5, and 10 years in PD group was 92.8%, 58.5%, and 0%, respectively. Similarly, graft survival at 1, 5, and 10 years in KT group was 98.7%, 90.2%, and 90.2%, respectively. Multivariate analysis showed body mass index (BMI) (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.82–0.93, p < 0.001), and albumin (HR 0.55, 95% CI 0.37–0.80, p = 0.002) were significant predictors of survival. In the 1st year, patient survival was better in PD than KT, but after adjustment for BMI and albumin, both short-term and long-term survival in elderly KT group was better than that of PD. Hence, elderly ESRD patients should not be barred from KT just because of age.
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	Role of blood oxygen level-dependent MRI in differentiation of acute renal allograft dysfunction	p. 441
	Hira Lal, Ezaz Mohamed, Neelam Soni, Priyank Yadav, Manoj Jain, Dharmendra Bhadauria, Anupma Kaul, Narayan Prasad, Amit Gupta, RK Sharma DOI:10.4103/ijn.IJN_43_18   Early graft dysfunction after renal transplantation manifests as acute rejection (AR) or acute tubular necrosis (ATN). Blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging is a noninvasive method of assessing tissue oxygenation, which may be useful for predicting acute allograft dysfunction. This was a prospective study involving 40 patients scheduled for renal transplantation from August 2012 to August 2014. In addition, 15 healthy donors were also enrolled in this study. All recipients underwent BOLD MR imaging (MRI) and R2* mapping 10–20 days after transplant, and additionally within 48 h of biopsy if there was any evidence of graft dysfunction. The healthy donors underwent BOLD MRI 1–2 days before surgery. The biopsies were grouped into AR, ATN, and no evidence of AR or ATN. The mean medullary R2*, cortical R2*, corticomedullary gradient, and medullary: cortical R2* ratio were compared between groups using one-way analysis of variance. Spearman's correlation and multinomial linear regression were applied to determine the influence factors of R2* value. Overall, nine patients had graft dysfunction. Six were reported as AR, two as ATN, and one as no evidence of ATN or rejection. The mean medullary and cortical R2* were significantly higher in ATN group compared with AR and normal group, whereas the mean medullary and cortical R2* of AR group were significantly lower than normal group. The corticomedullary gradient of AR group was significantly lower compared with ATN and normal group. Medullary R2*:cortical R2* ratio was significantly lower in AR group compared with normal group. No significant difference was noted between the 15 donors and patients with normal graft function. R2* values on BOLD MRI are significantly decreased in AR allografts and increased in an early stage of ATN allografts, suggesting that BOLD MRI can become a valuable tool for discriminating between AR and ATN.
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	Prevalence and clinical correlates of white coat effect in patients with chronic kidney disease and the role of automated blood pressure device in its assessment	p. 448
	Srinivas Shenoy, Shankar Prasad Nagaraju, Nileshwar R Rau, Ravindra A Prabhu, Uday Venkat Mateti, Dharshan Rangaswamy, Indu R Rao, Karan Saraf DOI:10.4103/ijn.IJN_418_17   Context: Hypertension in chronic kidney disease (CKD) is an important modifiable cardiovascular risk factor. Patients with CKD can have clinically significant white coat effect (WCE), making routine clinic blood pressure (BP) measurements an unreliable indicator of actual BP control. Automated BP monitoring is useful in identifying WCE. The utility of automated BP monitoring has seldom been part of clinical practice in developing countries. Aim: The goal of this study was to estimate the prevalence and determinants of WCE in adult patients with CKD in an outpatient setting using an automated BP device. Materials and Method: In this prospective observational study, patients with CKD attending the nephrology clinic over a period of 6 months (January 2016 to July 2016), who were suspected to have WCE by the treating physician, were assigned to measurement of BP by both the standardized manual BP recording by a single nephrologist and with automated machine as per a defined protocol. Clinical, demographic characters that would influence outcomes were also studied. Results: Among 118 patients with CKD with suspected WCE, 57.6% showed WCE. The mean systolic and diastolic BPs were significantly lower with automated machine when compared with manual BP recordings in patients with WCE (p = 0.04). WCE was seen in all stages of CKD. Occurrence of WCE in CKD was not dependent on factors such as old age, sex, diabetes mellitus, or smoking status in our study. Conclusion:WCE is a highly prevalent and underdiagnosed entity in patients with CKD. Automated machine is a useful and time-saving tool in detection of WCE in patients with CKD attending the outpatient clinic and guide management.
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	Acute pyelonephritis: A single-center experience	p. 454
	L Umesha, SM Shivaprasad, EN Rajiv, MM Satish Kumar, V Leelavathy, CG Sreedhara, MR Niranjan DOI:10.4103/ijn.IJN_219_16   Acute pyelonephritis (APN), although a common clinical entity, still not much is known about the clinical profile in the Indian scenario. We prospectively collected clinical, biochemical, and radiological data of patients hospitalized with a diagnosis of APN from March 2014 to June 2016. A total of 296 cases were included in the study. Mean age was 53.85 ± 9.78 years. Male to females ratio was 1.93:1. Among the risk factors recognized for complicated pyelonephritis (PN), diabetes mellitus (DM) (54.4%) was the most common factor followed by renal calculi (14.4%), benign prostatic hyperplasia (6.7%), immunocompromised state (3.3%), stricture urethra and meatal stenosis (3.3%), and neurogenic bladder (2%). Urinary culture was negative in 153 (51.7%) and positive in 143 patient (48.3%). Most common organism isolated was Escherichia coli (29.7%), followed by Klebsiella pneumoniae (5.4%), pseudomonas (5.4%), Enterococcus (4.4%), and Proteus in 10 (3.4%). Serum creatinine of more than 1.5 mg/dl at admission was seen in 96.3% patients; 40% of them had underlying chronic kidney disease with DM being the most common. Multiorgan dysfunction either at admission or during the course in hospital stay was seen in 31.8% patients. Twelve (2%) had emphysematous PN. Six patients had Class II, 4 had Class III, 1 with Class I, and another with Class IV. A total of 18 deaths were noted (6.1%). Hemoglobin <10 g/dl, serum creatinine at admission >1.5 mg/dl, HbA1c% >10%, and immunosuppression had statistically significant association with the development of multiorgan dysfunction on univariate analysis, but on multivariate analysis, only hemoglobin, HbA1c%, and immunosuppression reached statistical significance. Even with attributable risk of mortality, only hemoglobin, HbA1c%, and immunosuppression reached statistical significance on multivariate analysis. HbA1c% adds to the predictive parameters to recognize at-risk patients to intensify the treatment and avoid complications.
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CASE REPORTS
	Hepatitis C virus-associated membranoproliferative glomerulonephritis treated with directly acting antiviral therapy	p. 462
	S Nayak, A Kataria, MK Sharma, A Rastogi, E Gupta, A Singh, SC Tiwari DOI:10.4103/ijn.IJN_235_17   Hepatitis C virus (HCV) infection has been shown to affect kidneys with various histopathological pattern on the kidney biopsy. These commonly include a membranoproliferative glomerulonephritis (MPGN) pattern with mixed cryoglobulinemia (CG), thrombotic microangiopathy, membranous nephropathy, and vasculitis affecting medium and small vessels of the kidneys causing polyarteritis nodosa. It has been rarely associated with MPGN without detectable CG. We present one such patient who presented to us with HCV-associated MPGN without detectable CG, who recovered completely with directly acting antiviral therapy without any immunosuppression.
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	Systemic lupus erythematosus with linear IgA bullous dermatosis and renal vascular lesions: An extremely rare association	p. 465
	R Malipatel, V Gnanapriya, A Manocha, YK Inchara DOI:10.4103/ijn.IJN_200_17   We report a rare case of systemic lupus erythematosus presenting initially with cutaneous manifestations of linear IgA bullous dermatosis. Later the patient developed renal abnormalities due to thrombotic microangiopathy and lupus nephritis with inflammatory necrotizing vasculitis. Paucity of immune deposits was observed on Immunofluorescence. This association of SLE with these cutaneous and renal lesions is rarely reported in the literature.
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	Xanthogranulomatous pyelonephritis: Intrahepatic and intrathoracic extension	p. 468
	U Anandh, N Birajdar, R Kumar, S Babu DOI:10.4103/ijn.IJN_213_17   A 32-year-old female presented to us with worsening cough and expectoration, low-grade fever, and malaise for 3 months. She gave a history of pregnancy loss secondary to urinary tract infection (UTI) a year back. At that time, she was told to have an obstructive right renal calculus. She also had a history of recurrent UTI in the past 1 year. She had no other comorbidities. Her clinical evaluation revealed an enlarged right kidney and reduced air entry in the right hemithorax. Radiological investigations revealed a large right kidney invading into the inferior surface of the right lobe of the liver and the right pleural space. A clinical diagnosis of xanthogranulomatous pyelonephritis was made, and she was advised nephrectomy. Intraoperatively, the right kidney was found to invade both the right lobe of the liver and the right pleural cavity through a right diaphragmatic defect. Histopathology of the kidney revealed the presence of foamy histiocytes suggestive of xanthogranulomatous pyelonephritis. Invasive xanthogranulomatous pyelonephritis is known, however, invasion into the extra-abdominal structures has not been reported in the literature. Our case is a rare manifestation of a rare clinical entity – xanthogranulomatous pyelonephritis.
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	Crystalline nephropathy in renal transplant: A series of 4 cases	p. 472
	K Mnif, S Yaich, M Mars, K Kammoun, F Fendri, K Charfeddine, F Jarraya, T Boudawara, J Hachicha DOI:10.4103/ijn.IJN_76_17   Crystals are particles of endogenous inorganic or organic composition that can trigger kidney injury when deposited or formed inside the kidney. The most common forms of crystalline nephropathies (CNs) are nephrocalcinosis and oxalate nephropathy. The causes of early allograft dysfunction are changing constantly, and recently calcium oxalate (CaOx) crystal deposition has been added to this list. CaOx deposition in renal allograft is important and probably under-recognized cause of delayed graft function that requires adequate awareness with early intervention to improve the allograft outcome. Here, we describe four cases of irreversible renal graft injury due to CNs.
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	Allopurinol-induced drug reactions with eosinophilia and systemic symptoms syndrome with interstitial nephritis	p. 477
	T Aatif, J Fatihi, H El Annaz, O Qamouss DOI:10.4103/ijn.IJN_166_17   Allopurinol-induced drug reactions with eosinophilia and systemic symptoms (DRESS) is a severe illness related to hypersensitivity syndrome characterized by fever, skin rash, lymph node enlargement, hematological abnormalities, especially eosinophilia and atypical lymphocytosis, and single or multiple organ involvement. The syndrome is difficult to diagnose in view of its clinical heterogeneity and long latency period within 8 weeks after start treatment. We report a case of DRESS syndrome in a 64-year-old man, induced by allopurinol treatment for asymptomatic hyperuricemia, started 8 weeks earlier but stopped only 3 days after because of the onset of rash. The diagnosis was retained due to combining of interstitial nephritis with the clinical findings of fever, skin rash, cervical lymphadenopathy, eosinophilia, and reactivation of human herpesviruses specifically HHV-6. The glucocorticoids were started to relieve hypersensitivity. Five days later, the patient became afebrile, and the rash improved significantly. However, interstitial nephritis with renal function impairment progressed to severe azotemia, and even anuria requiring hemodialysis. Allopurinol-induced DRESS syndrome is associated with significant mortality, and care must, therefore, be exercised when given this drug.
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	Autosomal dominant polycystic kidney disease: Presence of hypomorphic alleles in PKD1 Gene	p. 482
	S Pandita, D Khullar, R Saxena, IC Verma DOI:10.4103/ijn.IJN_236_17   Autosomal dominant polycystic kidney disease is characterized by multiple cysts in both kidneys manifesting in adult life. In general, the disorder is caused by a pathogenic variant in one allele of PKD1 or PKD2 genes, while the other allele is normal. Pathogenic variants in both the alleles are rare and have variable phenotypes, from lethal or perinatal presentation to a mild form in later adulthood, depending on the type of variant. Here, we describe a proband with two variants (p.Thr1773Ile and p.Ala1871Thr in trans) in PKD1 gene, who presented with disease at age 24 years. Both the parents and one brother had a variant in one allele, the other being wild type only and had normal ultrasound findings. Segregation studies suggest that both the variants may act as "hypomorphic" or "incompletely penetrant" alleles and acting together resulted in haploinsufficiency of protein PC1 in renal cells, leading to cystogenesis in the proband. The consequences of the presence of two hypomorphic variants have been poorly documented in literature. We reviewed the few published cases having two hypomorphic variants and the data conform to the conclusions that we reached by study of the family described. It is emphasized that to resolve the significance of suspected hypomorphic variants, segregation studies in the parents and siblings are essential.
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	An unusual association of renal cell carcinoma and renal malakoplakia with focal segmental glomerulosclerosis in an elderly patient	p. 485
	M Vijayan, P Koshy, R Parthasarathy, M Mathew, G Abraham DOI:10.4103/ijn.IJN_289_17   The association of malignancy and glomerulonephritis may be missed, especially in elderly patients. Here, we report a case of eosinophilic variant of renal cell carcinoma and renal parenchymal malakoplakia discovered on renal biopsy in a patient with steroid-dependent nephrotic syndrome. The presence of malakoplakia in our biopsy was probably due to systemic steroid therapy for glomerulonephritis, presence of concomitant asymptomatic urinary tract infection, and/or history of diabetes mellitus. The patient had remission of proteinuria following laparoscopic removal of the tumor, indicating probable remission of glomerulonephritis.
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	Kidney transplantation from a hepatitis C virus-positive donor to a hepatitis C virus-negative recipient	p. 488
	M Kamalkiran, V Ravikiran, C Shashidhar, K. V. R Prasad, V Yeldandi DOI:10.4103/ijn.IJN_267_17   Kidney transplantation from a hepatitis C virus (HCV)-positive donor to an HCV-negative recipient till recently has been a contraindication. In view of the excellent sustained virological response (SVR) rates with directly acting antiviral agents, HCV-positive donors are being considered for the HCV-negative recipients in a few centers. We report the successful transplantation of an HCV-negative recipient transplanted with an HCV-positive donor kidney. Donor was treated with sofosbuvir and ribavirin for 12 weeks. At 10th and 16th weeks of starting treatment, her HCV-RNA PCR was negative. Three weeks later, transplantation was performed with basiliximab induction and triple immunosuppression with tacrolimus, mycophenolate, and prednisolone. The recipient was administered sofosbuvir and ribavirin for 12 weeks. He attained good graft function with a stable creatinine. His serial alanine transaminases were normal on 3rd, 6th, and 12th months, respectively. Six months posttransplant his anti-HCV antibody, and HCV-RNA PCR were negative.
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LETTERS TO EDITOR
	Cystinuria in a 13-Month-Old girl with absence of mutations in the SLC3A1 and SLC7A9 genes	p. 490
	MD Al-Mendalawi DOI:10.4103/ijn.IJN_46_18
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	Improving crossmatch techniques and graft outcomes	p. 491
	L Vincent DOI:10.4103/ijn.IJN_362_17
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	Estimated glomerular filtration rate using creatinine-based chronic kidney disease epidemiology collaboration equation	p. 492
	AA Rani, V Viswanathan DOI:10.4103/ijn.IJN_439_17
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