Methylation of Cdkn1c may involve in the regulation of tooth development through cell cycle inhibition

Abstract

Cdkn1c, a member of the Cip/Kip cyclin-dependent kinase inhibitor family, is critically involved in regulating cell cycle and cellular differentiation during development in mammals. However, the functional role of Cdkn1c and the underlying mechanisms by which Cdkn1c affects odontogenesis remain largely unknown. In our study, we found that Cdkn1c expression dynamically changes from embryonic day 11.5 (E11.5) to postnatal day 3 (P3), and exhibits tissue-specific expression profiles. Evaluation of CDKN1C protein by immunohistochemistry and western blot, revealed that CDKN1C protein expression peaks at P3 and then is reduced at P5 and P7. Interestingly, we observed that CDKN1C expression is higher in immature odontoblasts than preodontoblasts, is lower in mature odontoblasts, and is practically absent from ameloblasts. We evaluated cell cycle progression to further investigate the mechanisms underlying CDKN1C-mediated regulation of odontogenesis, and found that pRB, cyclin D1 and CDK2 expression decreased from P1 to P3, and reduced at P5 and P7. In addition, we observed increased methylation of KvDMR1 at P1 and P3, and reduced KvDMR1 methylation at P5 and P7. However, the methylation levels of Cdkn1c-sDMR were relatively low from P1 to P7. In summary, we demonstrated that Cdkn1c expression and methylation status may be involved in early postnatal tooth development through regulating the cell cycle inhibition activity of Cdkn1c. Notably, Cdkn1c expression and methylation may associate with cell cycle exit and differentiation of odontoblasts.

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Disparities in the Use of Programmed Death 1 Immune Checkpoint Inhibitors

AbstractAmid growing excitement for immune checkpoint inhibitors of programmed death protein 1 (anti‐PD1 agents), little is known about whether race‐ or sex‐based disparities exist in their use. In this observational study, we constructed a large and mostly community‐based cohort of patients with advanced stage cancers, including melanoma, non‐small cell lung cancer (NSCLC), and renal cell carcinoma, to compare the odds of receiving systemic treatment with or without anti‐PD1 agents by race and by sex. In multivariable models that adjusted for age, stage, and number of prior anticancer therapies, we found no significant race‐based disparities in anti‐PD1 treatment. However, among patients with NSCLC, males had significantly higher odds of receiving anti‐PD1 treatment compared with females (odds ratio 1.13, 95% confidence interval 1.02–1.24, p = .02). This finding suggests that as anti‐PD1 agents enter the market to transform patient care, it will be critical to monitor for disparities in the use of these drugs.

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Seminoma with Neoplastic Meningitis Treated with Craniospinal Irradiation

AbstractPure seminoma is a histological subtype of testicular cancer that accounts for 50% of testicular germ cell tumors. It has a very low rate of metastasis to the central nervous system, with only one previously reported case of neoplastic meningitis (cancer that has spread to the cerebrospinal fluid). Traditionally, neoplastic meningitis has an ominous prognosis when associated with primary tumors that commonly spread to the leptomeninges, like breast and lung. This article highlights a unique case of pure seminoma with neoplastic meningitis and illustrates the effectiveness of craniospinal irradiation as a treatment modality.

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Is the pneumatisation of the maxillary sinus following tooth loss a reality? A retrospective analysis using cone beam computed tomography and a customised software program

Abstract

Objectives

To compare the dimensions of maxillary sinuses in dentate and edentulous patients using cone beam computed tomography (CBCT) scans and a customised software program.

Materials and methods

This study comprised CBCTs of 50 dentate and 50 edentulous posterior maxillae. The observers drew two planar curves in all included sinuses in the frontal, sagittal and axial planes of the respective CBCT scans. The volume (mm³), surface (mm²) and maximum diameter (mm) of the sinuses were calculated using a custom-made software program. The variables analysed were the influence of the state of dentition on sinus dimensions (primary outcome) and the influence of age, gender and side on sinus dimensions; the time needed for analysis; and the intra- and inter-observer agreement (secondary outcomes).

Results

There was no difference in sinus dimensions between dentate and edentulous posterior maxillae. Males had significantly (p < 0.05) greater volume, surface and diameter than females. Strong intra- and inter-observer agreement (Pearson correlation) was found for the calculated sinus dimensions. The time needed per analysis was less than 4 min for both observers.

Conclusions

Being edentulous did not have an impact on the sinus dimensions, suggesting that there is no ongoing pneumatisation in the sinus after tooth loss. Males had larger sinuses than females in a population older than 30 years.

Clinical relevance

Following tooth loss in the posterior maxilla, vertical bone height is primarily lost due to resorption of the alveolar crest, and not due to pneumatisation of the maxillary sinus. The customised software program was found to be user-friendly and efficient.

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Determining phytolith-occluded organic carbon sequestration using an upgraded optimized extraction method: indicating for a missing carbon pool

Abstract

Phytolith-occluded organic carbon (PhytOC) is considered one of the most promising terrestrial carbon (C) sinks. Different methods are used for phytolith extraction from wet-ashing techniques and the subsequent determination of PhytOC content from soil. This is in order to optimize the wet-ashing techniques and to improve estimation accuracy of C sequestration potential of phytoliths from soil. Results show that the organic matter removal and carbonate removal protocol, applying sonication, has a significant effect on phytolith extraction. Namely, the sequential removal of first organic matter and then carbonates applied to such methods could eliminate greater than 17.14, 46.68, and 26.17% extraneous material compared to other methods. Moreover, phytoliths extracted using methods that apply sonication eliminated 7.49, 42.70, and 17.57% more extraneous material than methods that did not. Additionally, the procedure associated with the second oxidation step significantly influenced the determination of PhytOC content, that is, 29.34, 33.75, 26.41, and 64.64% of excess organic C were oxidized during this step. The upgraded optimal method we recommend for phytolith extraction in association with wet-ashing techniques and the subsequent determination of PhytOC content is therefore to first apply sonication, then the second oxidation step, and finally the removal of organic matter. Using this optimal upgraded method, we estimated the C sequestration potential of phytoliths from the soil of slash pine in China at 0.51 Mt. C. Furthermore, using this upgraded optimal method increased the precision of the carbon sequestration potential of phytoliths from soil by up to 63.83%.

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Laser pulpotomy—an effective alternative to conventional techniques—a systematic review of literature and meta-analysis

Abstract

The aim of this systematic review and subsequent meta-analysis was to elaborate the efficacy of laser pulpotomy over the formocresol pulpotomy of human primary teeth. Published materials in the MedLine were looked for through "PUBMED" and "PUBMED CENTRAL". The MESH terms of "Laser", "Pulpotomy", "Primary teeth", and "Children" were used to carry the search from the years 1999 to 2017. Collected data were assessed by four investigators using inclusion and exclusion criteria in order to select those studies with precise method targeted. Only clinical trials on all types of lasers were included for this systematic reviews but only four articles were used for the meta-analysis as the rest did not meet the requirements. Statistical analysis was conducted to see the differences. Seventeen articles completely fulfilled the inclusion criteria of this study. In general, high clinical, radiographic, and histopathological success rates were reported in laser groups in comparison to other assessed methods. Meta-analysis indicated that except at 36 months, in all other time intervals, Laser proved better or close results to formocresol. At 36 months, laser showed better clinical results. Laser may be considered as an adjuvant alternative for vital pulp therapy on human primary teeth but due to the limited number of high-quality clinical research articles on laser-assisted pulpotomy, various types of laser application methods, and different follow-up periods, reaching a net consensus is still challenging.

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Metabolic Alterations in Patients with Pheochromocytoma

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0649-0960

Metabolic alterations in patients with hormonally active pheochromocytoma/paraganglioma (PPGL) have been described early on in the literature. The initial findings were related to disturbed glucose homeostasis and lipolysis activation, as well as elevated metabolic rates in affected patients. Similarly, from early autopsy reports, the presence of brown adipose tissue had been noted in PPGL patients. In more recent years, changes in body weight, fat mass and distribution have been analyzed in more detail in addition to activity of brown adipose tissue based on functional imaging techniques. Over the last decades, several larger case series and cohort studies have contributed towards the elucidation of possible mechanism contributing to these clinical observations. Herein, we summarize the clinical and experimental data regarding metabolic alterations and related clinical manifestations in PPGL patients.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Global trends and future prospects of food waste research: a bibliometric analysis

Abstract

The unregulated discharge reams of food waste (FW) causes severe resource loss and environmental pollution. In the present study, a bibliometric analysis was used for research activities and tendencies of food waste from 1991 to 2015. The results indicated that the amount of FW research continually grew by the years, and the number of publications rose significantly from 2012. Bioresource Technology and Waste Management were the two most frequently published journals in the field of FW research. China took a leading position and had a high h-index (38) out of 94 countries/territories, followed by the USA and South Korea. Presently, anaerobic digestion for methane and dark fermentation for hydrogen production are the mainstream techniques in FW disposal. Lactic and ethanol fermentation from FW received more and more attention in recent years. Life cycle assessment (LCA) was an ever-increasingly popular evaluation method for FW-related research. Moreover, cluster analysis indicated microbial community structure, food security, leachate, and pathogens were also the research hotspots.

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Beneficial effects of dietary silver nanoparticles and silver nitrate on broiler nutrition

Abstract

This study was conducted to investigate the growth modulatory effects of dietary supplementation with silver nanoparticles (Ag NPs) and Ag nitrate on broiler chickens. Thirty 15-day-old chicks were equally divided into the control group (fed basal diets), the Ag-nano group (fed basal diets supplemented with 50 ppm/kg of Ag NPs for 12 d), and the Ag nitrate group (fed basal diets supplemented with 100 ppm/kg Ag nitrate for 12 days). Chicks fed Ag NPs showed increased body weight gain and muscle weight, improved feed efficiency, and increased ash digestibility, while Ag digestibility tend to increase but not significant. Plasma triiodothyronine contents, and muscle Ag and nitrogen contents as well as a significant increase in the following mRNA levels in muscle tissue: insulin-like growth factor-1 (IGF1), glucose transporters (Glut1, Glut3), citrate synthase (CS), and glutathione peroxidase (GPx), whereas the atrogin-1, fatty acid synthase (FAS), acetyl CoA carboxylase (ACC), lactate dehydrogenase (LDH), and carnitine palmitoyl transferase 1A (CPT1A) mRNA levels were unchanged. However, these chicks exhibited decreased levels of plasma cholesterol, triglyceride, and glucose. Dietary supplementation with Ag NPs improved the growth performance of broiler chickens.

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Serum calprotectin correlates with risk and disease severity in psoriasis patients and the decrease of calprotectin predicts better response to tumor necrosis factor inhibitors

OBJECTIVE: This study aimed to investigate the correlation of serum calprotectin expression with risk and severity of psoriasis, as well as its predictive value for clinical response to tumor necrosis factor inhibitors (TNFi) treatment in psoriasis patients.

PATIENTS AND METHODS: 72 psoriasis patients and 70 health controls (HCs) were enrolled. Blood samples were collected, and serum calprotectin was determined by commercial enzyme-linked immuno sorbent assay (ELISA). All patients were treated by TNFi treatment, and followed up at 6 months, and the last follow-up date was 2016/11.

RESULTS: Calprotectin level was elevated in psoriasis patients compared to HCs (p < 0.001), and it disclosed a good diagnostic value of psoriasis with area under curve (AUC) 0.872, 95% CI: 0.810-0.935. Calprotectin expression was positively associated with Psoriasis Area and Severity Index (PASI) score (R = 0.452, p < 0.001), while it was not associated with BSA (R = 0.125, p = 0.297). 58.3% patients achieved PASI75 and 43.1% patients achieved PASI90 at M6. Calprotectin was decreased during the 6-month treatment (p < 0.001). Changes of calprotectin during the first month (∆calprotectin (M0-M1)) in PASI75 group were more than that of non-PASI75 group (p < 0.001). Also, multivariate logistic analysis revealed that ∆calprotectin (M0-M1) (p = 0.001) was an independent factor for PASI75 achievement at M6 after TNFi treatment, while pre-systemic biologic treatment (p = 0.001) was an independent factor for non-PASI75 achievement.

CONCLUSIONS: Serum calprotectin expression is correlated with risk and severity of psoriasis, and the decrease of calprotectin during the first month could predict better clinical response to TNFi treatment in psoriasis patients

L'articolo Serum calprotectin correlates with risk and disease severity in psoriasis patients and the decrease of calprotectin predicts better response to tumor necrosis factor inhibitors sembra essere il primo su European Review.

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Inactivation of influenza A virus via exposure to silver nanoparticle-decorated silica hybrid composites

Abstract

Influenza A virus (IFV-A) is one of the main cause of seasonal flu and can infect various of host species via the reassortment of segmented RNA genomes. Silver nanoparticles (AgNPs) have been known as excellent antiviral agent against IFV. However, the use of free AgNPs has several major drawbacks, including the inherent aggregation among AgNPs and unwanted cytotoxic or genotoxic damages for human body via inhalation or ingestion. In this study, we assessed the efficacy of our novel ~ 30-nm-diameter AgNP-decorated silica hybrid composite (Ag30-SiO₂; ~ 400 nm in diameter) for IFV-A inactivation. Ag30-SiO₂ particles can inhibit IFV-A effectively in a clear dose-dependent manner. However, when real-time RT-PCR assay was used, merely 0.5-log₁₀ reduction of IFV-A was observed at both 5 and 20 °C. Moreover, even after 1 h of exposure to Ag30-SiO₂ particles, more than 80% of hemagglutinin (HA) damage and 20% of neuraminidase (NA) activities had occurred, and the infection of Madin-Darby Canine Kidney (MDCK) cells by IFV-A was reduced. The results suggested that the major antiviral mechanism of Ag30-SiO₂ particles is the interaction with viral components located at the membrane. Therefore, Ag30-SiO₂ particles can cause nonspecific damage to various IFV-A components and be used as an effective method for inactivating IFV-A.

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Distribution of polybrominated diphenyl ethers in the atmosphere of the Pearl River Delta region, South China

Abstract

Air samples were collected from 26 air-monitoring stations located in the Pearl River Delta (PRD) and two in Shaoguan, South China, to investigate the spatial distribution and temporal changes in polybrominated diphenyl ethers (PBDEs) after the production and use of PBDE commercial formulations was restricted in China and the "dual transfer strategy" implemented by Guangdong Province. The spatial distribution of PBDEs was inhomogeneous in the PRD region, with concentrations ranging from 26.3 to 634 pg/m³ and a mean value of 105 pg/m³. The PBDE levels in the five western cities (Guangzhou, Foshan, Zhaoqing, Zhongshan, and Jiangmen) were markedly higher than those in the four eastern cities (Dongguan, Huizhou, Shenzhen, and Zhuhai). BDE-209 was the predominant congener, accounting for 57.3–89.8% of the total measured PBDEs in this study. The proportion of penta- and nona-BDE congeners in the four eastern cities was markedly higher than those in five western cities. Principal component analysis showed that this elevation might be related to the debromination of BDE-209 during the thermal treatment process of products when PBDEs are used as flame retardants. Although the PBDE levels found in this study were markedly lower than those reported in previous studies, further efforts are still needed to clarify if there was a decreasing trend for PBDEs in the atmosphere of the PRD, in view of the increasing trends of PBDEs found by other researchers in mangrove sediments from Hong Kong and the Pearl River estuary in 2014 and 2015.

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A comparison of orofacial profiles in 5- and 10-year-old Swedish children with and without cleft lip and/or palate

Abstract

Objectives

The objectives of this study were to assess orofacial profiles in 5- and 10-year-old children with cleft lip and/or palate (CL/P) compared to controls and to estimate a possible association between orofacial dysfunction and caries frequency.

Materials and methods

A total of 133 children with CL/P (77 5-year-olds and 56 10-year-olds) and 308 controls (142 5-year-olds and 166 10-year-olds) were included in the study. Orofacial function was evaluated with Nordic Orofacial Test-Screening (NOT-S), and caries were scored according to the International Caries Detection and Assessment System (ICDAS).

Results

The total NOT-S score was higher in children with CL/P compared to controls (mean 3.2 vs 0.9, p < 0.001). The domains frequently scored in CL/P children were speech (82%), face at rest (72%), and facial expression (58%). There was a significantly positive correlation between NOT-S scores and caries frequency.

Conclusions

Children with CL/P have impaired orofacial function compared to controls. There seems to be a correlation between orofacial function and caries.

Clinical relevance

Impaired orofacial function seen in children with CL/P can be one of many risk factors for caries development, and it is suggested to be a part of caries risk assessment.

https://ift.tt/2Lni1VA

Radiation-induced morphea—a rare but severe late effect of adjuvant breast irradiation

Abstract

Background

Radiation-induced morphea (RIM) is a circumscribed localized scleroderma that occurs most often in the breast. After an asymptomatic period of one month to several years, the symptoms (circumscribed inflammation, edema, sclerosis) often arise suddenly and cannot be clinically distinguished from a local recurrence in the form of inflammatory carcinoma.

Case

We present a case of a 74-year-old woman who developed this rare and serious local side-effect in connective tissue following neoadjuvant CDK 4/6 inhibitor abemaciclib (Verzenio®) and aromatase inhibitor anastrozole (Arimidex®) therapy and subsequent radiation therapy of the breast.

Conclusions

Little is known about risk factors and pathogenesis of RIM. Here we describe the first case of RIM following immunotherapy. The diagnosis is based on clinical appearance and histopathological examination. Treatment should be initiated in the inflammatory stage in order to prevent or delay irreversible fibrosis and atrophy of the breast.

https://ift.tt/2NlHIXb

Effect of petroleum-derived substances on life history traits of bird cherry-oat aphid ( Rhopalosiphum padi L.) and on the growth and chemical composition of winter wheat

Abstract

The aim of the study was to determine the effects of various petroleum-derived substances (PDSs), namely petrol, diesel fuel, and spent engine oil, on life history traits of the bird cherry-oat aphid Rhopalosiphum padi L., and on the growth and chemical composition of its host plant—winter wheat Triticum aestivum L. Each substance was tested separately, using two concentrations (9 and 18 g kg⁻¹). Plants were cultivated in both control and contaminated soils. In early October 2013, soil was contaminated and after 1 week, winter wheat seeds, 'Batuta' cultivar, were sown. In early June 2014, observations of the effect of petroleum-derived substances on traits of three successive generations of aphids were conducted. Aphids were inoculated separately on leaves using cylindrical cages hermetically closed on both sides. Contamination of aphid occurred through its host plant. Results showed that all of the applied petroleum-derived substances have a generally adverse effect on the developmental parameters in aphids, resulting in the decrease of its fecundity, shortening its average life span, and most often lowering of the population intrinsic growth rate. PDSs caused the limitation of growth in wheat plants; whereas, changes in nutrient contents and heavy metals depended on the part of the plant analysed, the substance applied, and on its dose. The negative relationships between the contents of both some macro-elements (Ca, K, P) and heavy metals (Mn, Cd, Cu, and Zn) and the developmental parameters of particular generations of R. padi were observed. The high susceptibility of R. padi to the presence of PDSs in the substrate for the host plant should be emphasised—the clear-cut changes in the life span and fecundity, with relatively small changes in the chemical composition of the plant, constitute an evident indication that the developmental parameters of aphids have the potential for the use as bio-indicator to evaluate the state of the environment contaminated by PDSs.

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Comparison of botulinum toxin and propranolol for essential and dystonic vocal tremors

OBJECTIVES: Vocal tremors, which cause social difficulties for patients, may be classified as resting or action tremors. Of the vocal action tremors, essential and dystonic tremors are the most common. Botulinum toxin and oral medications have been used to treat vocal tremors, but no comparative clinical trials have been performed. The aim of this study was to compare the effects of botulinum toxin injection and the oral administration of propranolol in the treatment of essential and dystonic vocal tremors. METHODS: This clinical trial recruited 15 patients, divided into essential and dystonic vocal tremor groups. Patients in both groups received successive treatment with botulinum toxin and propranolol. The treatments were administered at different times; the order of treatment was randomly selected. Patients were assessed with flexible nasofibrolaryngoscopy and with perceptual and acoustic voice evaluations. A statistical significance level of 0.05 (5%) was used. RESULTS: Botulinum toxin produced statistically significant improvements in perceptual measures of vocal instability in patients with dystonic vocal tremors compared with baseline values and treatment with propranolol. The acoustic measure of variability in the fundamental frequency was significantly lower in patients with dystonic vocal tremors after treatment with botulinum toxin. CONCLUSION: Essential and dystonic vocal tremors responded differently to treatment. Dystonic vocal tremors responded significantly to treatment with botulinum toxin but not oral propranolol. Essential vocal tremors did not respond significantly to either treatment, perhaps due to the small number of patients, which is a limitation of this research.

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Liver transplantation for acute liver failure due to antitubercular drugs – a single-center experience

OBJECTIVES: Patients receiving treatment for tuberculosis are at risk of developing acute liver failure due to the hepatotoxicity of antitubercular drugs. We aimed to describe our experience with liver transplantation from deceased donors in this situation. METHODS: We identified patients undergoing transplantation for acute liver failure due to antitubercular drugs in our prospectively maintained database. RESULTS: Of 81 patients undergoing transplantation for acute liver failure, 8 cases were attributed to antitubercular drugs during the period of 2006-2016. Regarding the time of tuberculosis treatment until the onset of jaundice, patients were on antitubercular drugs for a mean of 64.7 days (21-155 days). The model for end-stage liver disease (MELD) score of patients ranged from 32 to 47 (median 38), and seven patients underwent transplantation under vasopressors. The 1-year survival was 50%. Three patients died during the week following transplantation due to septic shock (including a patient with acute liver failure due to hepatic/disseminated tuberculosis), and the remaining patient died 2 months after transplantation due to pulmonary infection. There were 2 cases of mild rejection and 1 case of moderate rejection. Of the surviving patients, all were considered cured of tuberculosis after alternative drugs were given. CONCLUSION: Patients arrived very sick and displayed poor survival after deceased donor transplantation.

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Is subjective sleep evaluation a good predictor for obstructive sleep apnea?

OBJECTIVE: To compare subjective sleep evaluation obtained using four questionnaires with polysomnography results for individuals with and without obstructive sleep apnea. METHODS: Observational and analytical study in which individuals underwent polysomnography were studied retrospectively to investigate sleep disorders. We compared subjective data from a research database used to predict obstructive sleep apnea based on the STOP-BANG questionnaire, evaluation of excessive daytime sleepiness (Epworth Sleepiness Scale), sleep quality questionnaire (Mini Sleep Questionnaire) and Post-Sleep Data Collection Instrument with the self-reported total sleep time and sleep-onset latency for subjects with and without obstructive sleep apnea. RESULTS: The STOP-BANG questionnaire was a good predictor for the diagnosis of obstructive sleep apnea. However, the other instruments did not show a significant difference between healthy and sick individuals. Patients' perceptions of their sleep onset time were significantly lower than the polysomnographic data, but this difference remained for both subjects with and without obstructive sleep apnea. No difference was found between the subjective duration of sleep and the total sleep time assessed by polysomnography in either the healthy subjects or the patients. CONCLUSION: Except for the STOP-BANG questionnaire, subjective evaluation of sleepiness, sleep quality, perception of onset, and total sleep time are not important parameters for the diagnosis of obstructive sleep apnea, which reinforces the need for an active search for better management of these patients.

https://ift.tt/2JstT70

Transcriptional activity of oestrogen receptors in the course of embryo development

Oestrogens are well-known proliferation and differentiation factors that play an essential role in the correct development of sex-related organs and behaviour in mammals. With the use of the ERE-Luc reporter mouse model, we show herein that throughout mouse development, oestrogen receptors (ERs) are active starting from day 12 post conception. Most interestingly, we show that prenatal luciferase expression in each organ is proportionally different in relation to the germ layer of the origin. The luciferase content is highest in ectoderm-derived organs (such as brain and skin) and is lowest in endoderm-derived organs (such as liver, lung, thymus and intestine). Consistent with the testosterone surge occurring in male mice at the end of pregnancy, in the first 2 days after birth, we observed a significant increase in the luciferase content in several organs, including the liver, bone, gonads and hindbrain. The results of the present study show a widespread transcriptional activity of ERs in developing embryos, pointing to the potential contribution of these receptors in the development of non-reproductive as well as reproductive organs. Consequently, the findings reported here might be relevant in explaining the significant differences in male and female physiopathology reported by a growing number of studies and may underline the necessity for more systematic analyses aimed at the identification of the prenatal effects of drugs interfering with ER signalling, such as aromatase inhibitors or endocrine disrupter chemicals.

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Biochemical and clinical aspects of glycogen storage diseases

The synthesis of glycogen represents a key pathway for the disposal of excess glucose while its degradation is crucial for providing energy during exercise and times of need. The importance of glycogen metabolism is also highlighted by human genetic disorders that are caused by mutations in the enzymes involved. In this review, we provide a basic summary on glycogen metabolism and some of the clinical aspects of the classical glycogen storage diseases. Disruptions in glycogen metabolism usually result in some level of dysfunction in the liver, muscle, heart, kidney and/or brain. Furthermore, the spectrum of symptoms observed is very broad, depending on the affected enzyme. Finally, we briefly discuss an aspect of glycogen metabolism related to the maintenance of its structure that seems to be gaining more recent attention. For example, in Lafora progressive myoclonus epilepsy, patients exhibit an accumulation of inclusion bodies in several tissues, containing glycogen with increased phosphorylation, longer chain lengths and irregular branch points. This abnormal structure is thought to make glycogen insoluble and resistant to degradation. Consequently, its accumulation becomes toxic to neurons, leading to cell death. Although the genes responsible have been identified, studies in the past two decades are only beginning to shed light into their molecular functions.

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Corticosteroids and the brain

The brain is continuously exposed to varying levels of adrenal corticosteroid hormones such as corticosterone in rodents and cortisol in humans. Natural fluctuations occur due to ultradian and circadian variations or are caused by exposure to stressful situations. Brain cells express two types of corticosteroid receptors, i.e. mineralocorticoid and glucocorticoid receptors, which differ in distribution and affinity. These receptors can mediate both rapid non-genomic and slow gene-mediated neuronal actions. As a consequence of these factors, natural (e.g. stress-induced) shifts in corticosteroid level are associated with a complex mosaic of time- and region-dependent changes in neuronal activity. A series of experiments in humans and rodents have revealed that these time- and region-dependent cellular characteristics are also reflected in distinct cognitive patterns after stress. Thus, directly after a peak of corticosteroids, attention and vigilance are increased, and areas involved in emotional responses and simple behavioral strategies show enhanced activity. In the aftermath of stress, areas involved in higher cognitive functions become activated allowing individuals to link stressful events to the specific context and to store information for future use. Both phases of the brain's response to stress are important to face a continuously changing environment, promoting adaptation at the short as well as long term. We argue that a balanced response during the two phases is essential for resilience. This balance may become compromised after repeated stress exposure, particularly in genetically vulnerable individuals and aggravate disease manifestation. This not only applies to psychiatric disorders but also to neurological diseases such as epilepsy.

https://ift.tt/2JrcKum

Mitochondrial oxidative stress in obesity: role of the mineralocorticoid receptor

Obesity is a multifaceted, chronic, low-grade inflammation disease characterized by excess accumulation of dysfunctional adipose tissue. It is often associated with the development of cardiovascular (CV) disorders, insulin resistance and diabetes. Under pathological conditions like in obesity, adipose tissue secretes bioactive molecules called 'adipokines', including cytokines, hormones and reactive oxygen species (ROS). There is evidence suggesting that oxidative stress, in particular, the ROS imbalance in adipose tissue, may be the mechanistic link between obesity and its associated CV and metabolic complications. Mitochondria in adipose tissue are an important source of ROS and their dysfunction contributes to the pathogenesis of obesity-related type 2 diabetes. Mitochondrial function is regulated by several factors in order to preserve mitochondria integrity and dynamics. Moreover, the renin–angiotensin–aldosterone system is over-activated in obesity. In this review, we focus on the pathophysiological role of the mineralocorticoid receptor in the adipose tissue and its contribution to obesity-associated metabolic and CV complications. More specifically, we discuss whether dysregulation of the mineralocorticoid system within the adipose tissue may be the upstream mechanism and one of the early events in the development of obesity, via induction of oxidative stress and mitochondrial dysfunction, thus impacting on systemic metabolism and the CV system.

https://ift.tt/2NVIdbh

mTOR signaling in the arcuate nucleus of the hypothalamus mediates the anorectic action of estradiol

Current evidence suggests that estradiol (E2), the main ovarian steroid, modulates energy balance by regulating both feeding and energy expenditure at the central level, through the energy sensor AMP-activated protein kinase (AMPK). We hypothesized that the hypothalamic mechanistic target of rapamycin (mTOR) pathway, a well-established nutrient sensor and modulator of appetite and puberty, could also mediate the anorectic effect of E2. Our data showed that ovariectomy (OVX) elicited a marked downregulation of the mTOR signaling in the arcuate nucleus of the hypothalamus (ARC), an effect that was reversed by either E2 replacement or central estrogen receptor alpha (ERα) agonism. The significance of this molecular signaling was given by the genetic inactivation of S6 kinase B1 (S6K1, a key downstream mTOR effector) in the ARC, which prevented the E2-induced hypophagia and weight loss. Overall, these data indicate that E2 induces hypophagia through modulation of mTOR pathway in the ARC.

https://ift.tt/2JrcDPs

Ixazomib, Gemcitabine, and Doxorubicin in Treating Participants With Locally Advanced or Metastatic Kidney Cancer

Conditions:   Kidney Medullary Carcinoma;   Stage III Renal Cell Cancer AJCC v8;   Stage IV Renal Cell Cancer AJCC v8
Interventions:   Drug: Doxorubicin;   Drug: Gemcitabine;   Drug: Ixazomib
Sponsors:   M.D. Anderson Cancer Center;   National Cancer Institute (NCI)
Not yet recruiting

https://ift.tt/2LgLkMy

Intrathecal Neostigmine for Prevention of PDPH

Condition:   Post-Dural Puncture Headache
Interventions:   Drug: Neostigmine Methylsulfate;   Drug: Dextrose 5% in water
Sponsor:   Fayoum University Hospital
Not yet recruiting

https://ift.tt/2LoWBHs

Assessment of Graft Perfusion and Oxygenation for Improved Outcome in Esophageal Cancer Surgery

Conditions:   Anastomotic Leak;   Esophageal Cancer
Interventions:   Diagnostic Test: Indocyanine green angiography;   Diagnostic Test: Hemodynamic evaluation;   Diagnostic Test: Biological and pathological markers of ischemia
Sponsors:   University Hospital, Ghent;   Kom Op Tegen Kanker
Not yet recruiting

https://ift.tt/2LaBtI5

Prognostic factors in stereotactic body radiotherapy of lung metastases

Abstract

Purpose

The aim of this study was to evaluate prognostic factors in patients with lung metastases who undergo lung stereotactic body radiotherapy (SBRT).

Materials and methods

A total of 87 patients with 129 lung metastases who underwent SBRT between November 2004 and May 2012 were enrolled in this retrospective study. The patient collective consisted of 54 men (62.1%) and 33 women (37.9%); the median age was 65 years (range 36–88). The Karnofsky performance index was ≥70% (median 90%) for all cases, but one (60%). Adverse effects were categorized using the CTCAE 4.0 classification system. Retrospective analyses regarding patients' characteristics, progression-free survival (PFS), overall survival (OS), disease-specific survival (DSS), and local tumor control rates (LTC) were performed.

Results

On univariate and multivariate analysis OS, DSS, and PFS were significantly (p < 0.05) better for patients with ≤3 lung metastases; no extrathoracic metastases at the time of the SBRT; a gross tumor volume (GTV) <7.7 cm³ and patients that received a staging that included positron emission tomography with fluorine 18 fluorodeoxyglucose/computed tomography (FDG-PET/CT) imaging. Furthermore, a longer OS was observed if newly diagnosed metastases during follow-up were limited to the lung (median survival: 43.7 months versus 21.7 months; p = 0.023).

Conclusion

The number and pattern of metastases, and the size of the target volume are strong predictors for the outcome of patients receiving SBRT of lung tumors. FDG-PET/CT should be part of pretherapeutic staging before SBRT.

https://ift.tt/2Lk2xFa

Cosmetics, Vol. 5, Pages 44: A Green and Rapid Analytical Method for the Determination of Hydroxyethoxyphenyl Butanone in Cosmetic Products by Liquid Chromatography

Cosmetics, Vol. 5, Pages 44: A Green and Rapid Analytical Method for the Determination of Hydroxyethoxyphenyl Butanone in Cosmetic Products by Liquid Chromatography

Cosmetics doi: 10.3390/cosmetics5030044

Authors: Pablo Miralles Juan L. Benedé Aylén Mata-Martín Alberto Chisvert Amparo Salvador

An analytical method for the determination of hydroxyethoxyphenyl butanone, which is used as an alternative preservative in cosmetic products, has been developed and validated for the first time. The method is based on a simple ultrasound-assisted lixiviation of the analyte from the cosmetic matrix followed by liquid chromatography with UV spectrophotometric detection. Under optimized conditions, the method limit of detection and limit of quantification values were 30 and 90 &micro;g&middot;g&minus;1, respectively. The method was validated with good recovery values (86&ndash;103%) and precision values (RSD 0.2&ndash;4.7%). Finally, the proposed analytical method was successfully applied to 7 commercially available cosmetic samples including both lipophilic and hydrophilic matrices, such as moisturizing cream, sunscreen, shampoo, liquid hand soap, and make-up. Additionally, a laboratory-made cosmetic cream containing the target analyte was prepared and analyzed. The good analytical figures of merit of the proposed method, in addition to its environmentally-friendly characteristics, demonstrate its usefulness to perform the quality control of cosmetic products to ensure the safety of consumers.

https://ift.tt/2NRjtBj

Increasing soft tissue thickness does not affect trabecular bone score reproducibility: a phantom study

Abstract

Purpose

Trabecular Bone Score (TBS) provides an indirect score of trabecular microarchitecture from lumbar spine (LS) dual energy X-ray absorptiometry. Increasing soft tissue thickness artifactually reduces TBS values; we evaluated the effect of a fictitious increase of soft tissue thickness on TBS and bone mineral density (BMD) reproducibility on a phantom model.

Methods

A Hologic spine phantom was scanned with a QDR-Discovery W Hologic densitometer. Fresh pork rind layers of 5 mm were used to simulate the in-vivo soft tissues. For each scan mode (fast array [FA], array, high definition [HD]), 25 scans were consecutively performed without phantom repositioning, at 0 (no layers), 1 cm, 3 cm, and 6 cm of thickness. BMD and TBS reproducibility was calculated as the complement to 100% of least significant change.

Results

Both BMD and TBS reproducibility slightly decreased with increasing soft tissue; this difference was statistically significant only for BMD using HD modality (reproducibility decreased from 99.4% at baseline to 98.4% at 6-cm of thickness). TBS reproducibility was slightly lower compared to that of BMD, and ranged between 98.8% (array, 0 cm) and 97.4% (FA, 6 cm). Without taking into account manufacturer BMI optimization, we found a progressive decrease of TBS mean values with increasing soft tissue thickness. The highest TBS difference between baseline scan and 6 cm was −0.179 (−14.27%) using HD.

Conclusions

Despite being slightly lower than that of BMD, TBS reproducibility was not affected up to 6 cm of increasing soft tissue thickness, and was even less influenced by fat than BMD reproducibility.

https://ift.tt/2LiogtH

Molecular evaluation of a sporadic paraganglioma with concurrent IDH1 and ATRX mutations

Abstract

Purpose

Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors of neural crest origin. Germline or somatic mutations of numerous genes have been implicated in the pathogenesis of PPGLs, including the isocitrate dehydrogenase 1 (IDH1) gene and alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene. Although concurrent IDH1 and ATRX mutations are frequently seen in gliomas, they have never been reported together in PPGLs. The aim of this study was to characterize one paraganglioma with concurrent IDH1 and ATRX mutations identified by whole exome sequencing.

Methods

Leukocyte and tumor DNA were used for whole exome sequencing and Sanger sequencing. 2-hydroxyglurarate level and the global DNA methylation status in the tumor were measured. ATRX's cDNA transcripts were analyzed. Tyrosine hydroxylase (TH), HIF1α and ATRX staining, as well as telomere-specific FISH was also performed.

Results

The presence of a somatic IDH1 (c.394C>T, p.R132C) mutation and a concurrent somatic ATRX splicing mutation (c.4318-2A>G) in the current case was confirmed. Dramatic accumulation of 2-hydroxyglutarate was detected in the paraganglioma without the global DNA hypermethylation, and pseudohypoxia was also activated. Importantly, immunohistochemistry revealed negative TH staining in the tumor and the first exon region of TH gene was hypermethylated resulting in normal plasma metanephrines. The splicing ATRX mutation resulted in two transcripts, causing frameshifts. Immunohistochemistry revealed scarce ATRX staining in the tumor. Alternative lengthening of telomeres (ALT) was detected by FISH.

Conclusions

This case represents the first concurrence of IDH1 and ATRX mutations in PPGLs. Although relatively rare, a somatic R132C mutation of IDH1 might play a role in a small subset of sporadic PPGLs.

https://ift.tt/2LguSMr

Age at menarche and the risk of gestational diabetes mellitus: a systematic review and meta-analysis

Abstract

Purpose

Epidemiological studies had demonstrated that early age at menarche increased the risk of type 2 diabetes (T2DM), and gestational diabetes mellitus (GDM) shares many risk factors and features with T2DM. Thus, age at menarche may be a potential factor in the development of GDM. The aim of this study was to assess the association between age at menarche and the risk of gestational diabetes mellitus.

Methods

The databases of PubMed, Embase, Web of Science and Cochrane Library were searched up to June 2017.

Results

A total of 50,535 participants from five individual studies were included in the meta-analyses to evaluate the risk of GDM. Meta-analysis showed that women with menarche at an early age (≤11 years) had a higher GDM risk than those with menarche at age ≥12 years. (OR = 1.45, 95% CI = 1.26–1.68; P < .00001) There was low heterogeneity among the studies (Q = 6.4; P = 0.17; I^{2 =} 38).

Conclusions

This meta-analysis demonstrated that earlier menarche was strongly associated with an increased risk of GDM. A history of early age at menarche may help identify women at high risk of GDM and allow the implementation for the strategy of early prevention.

https://ift.tt/2LlckY4

Long-term effect of testosterone replacement therapy on bone in hypogonadal men with Klinefelter Syndrome

Abstract

Purpose

To assess different aspects of bone damage in untreated adult patients with Klinefelter Syndrome (KS) before and during testosterone replacement therapy (TRT).

Methods

Fifteen untreated hypogonadal men with KS and 26 control subjects (C) matched for age and BMI were recruited. Sex hormone levels were measured in all subjects. Lumbar spine (LS) and femoral (neck: FN and total hip: TH) bone mineral density (BMD), trabecular bone score (TBS), hip structure analysis (HSA) and fat measures (percentage of fat mass, android/gynoid ratio and visceral adipose tissue) were evaluated by DEXA. In KS patients, blood analysis and DEXA measurements were assessed at baseline and repeated yearly for three years during TRT.

Results

Fat measures were significantly higher in KS than C (p < 0.01). In contrast, mean LS, FN and TH BMD were significantly reduced in KS compared to C (p < 0.01), while there was no difference in TBS. HSA revealed a significantly lower cortical thickness and significantly higher buckling ratio in KS compared to C at all femoral sites (p < 0.01). In KS patients, TRT significantly increased BMD at LS only, but did not improve TBS and HSA parameters. Fat measures were inversely associated with TBS values, and TRT did not influence this relationship.

Conclusions

In untreated hypogonadal men with KS, lumbar and femoral BMD was reduced, and femoral bone quality was impaired. Adiposity seemed to have a detrimental effect on lumbar bone microarchitecture, as indirectly evaluated by TBS. However, TRT failed to remedy these negative effects on bone.

https://ift.tt/2uGkJ1o

Thyroid nodule ultrasound reports in routine clinical practice provide insufficient information to estimate risk of malignancy

Abstract

Purpose

Ultrasonographic characteristics of thyroid nodules play an important role in estimating the risk of malignancy (ROM). Guidelines mandate all thyroid nodules be characterized by six key ultrasonographic features to estimate the ROM. Our objective was to evaluate how frequently these characteristics were identified by radiologists and the ensuing utility to estimate ROM.

Methods

We retrospectively reviewed 1930 consecutive diagnostic thyroid ultrasound reports from a large community radiology practice. A total of 1339 individual patients were found to have one or more thyroid nodules. Each report was analyzed for six key ultrasonographic features. A utility score (UtS) was calculated (range 0–6) with a single point given for a comment on each feature.

Results

Of the 1339 patients, 75% of the studies reported more than one nodule (mean number of nodules = 3.4). Mean maximal diameter of the largest nodule per patient = 1.8 cm. The mean UtS was 2.57. Nodule size did not influence the UtS.: Nodule <1 cm (UtS: 2.53), 1–2 cm (UtS: 2.68) and >2 cm (UtS: 2.49). We believe a UtS of four or greater is needed to confidently estimate ROM: we found this in 13.7% of reports.

Conclusions

Our retrospective analysis of a large number of consecutive thyroid ultrasound reports in routine clinical practice suggests that the vast majority provide insufficient information to allow the clinician to risk stratify the nodules by estimating the ROM. This could lead to both over-diagnosis and over-treatment of benign/indolent thyroid lesions or under-diagnosis of clinically important thyroid cancers.

https://ift.tt/2uo3PFq

Is serum TSH a biomarker of thyroid carcinoma in patients residing in a mildly iodine-deficient area?

Abstract

Purpose

To investigate the association between the pre-operative serum TSH (s-TSH) level and differentiated thyroid carcinoma (DTC) in a mildly iodine-deficient area.

Methods

Patients undergoing surgery for thyroid nodular disease (TND) were included from three tertiary surgical departments. Data were collected from a national thyroid surgery database (THYKIR) and from patient charts. Individuals with overtly coexisting thyroid disorders were excluded for subgroup analyses. Patients were compared with the Danish background population, employing previous data from DanThyr, a study initiated to monitor the iodine fortification program in Denmark.

Results

Nine-hundred ninety-eight patients [cases/controls: 265/733; female/male: 794/204; age (mean ± SD): 51 ± 15 years] were included. S-TSH was significantly higher in the DTC group [median (IQR): 1.3 (0.9–1.9 mIU/L)] compared with the benign TND group [0.9 (0.6–1.5 mIU/L)] (p < 0.0001). The median s-TSH in the background population was similar to that found among DTC patients (p = 1.00), but markedly higher than the s-TSH level in the benign TND group (p < 0.0001). There was no association between s-TSH and DTC disease stage (p = 0.08–0.87).

Conclusions

s-TSH was significantly higher in patients with DTC than in those with benign TND. However, this difference can be explained by abnormally lower s-TSH level in the latter group, probably caused by subtle nodular functional autonomy. Due to the huge overlap and the small difference in median s-TSH between patients with benign and malignant TND, s-TSH is not suitable as a biomarker of DTC in a clinical setting.

https://ift.tt/2LoF81Q

Multiple benefits from dual release hydrocortisone: a “hard” view from bones

https://ift.tt/2LjJcnz

Successful surgery of the hypothalamic region: Yes, we can!

https://ift.tt/2Lcnqlv

High Ki-67 index in fine needle aspiration cytology of follicular thyroid tumors is associated with increased risk of carcinoma

Abstract

Purpose

Preoperative distinction of follicular thyroid carcinoma (FTC) from follicular thyroid adenoma (FTA) is a diagnostic challenge. Our aim was to investigate whether the Ki-67 proliferation index in fine needle aspiration material can contribute to the diagnosis of FTC.

Methods

We analyzed retrospectively cytological Ki-67 index determined in routine clinical setting and clinical data for 61 patients with FTC, 158 patients with FTA and 15 patients with follicular tumor of uncertain malignant potential (FT-UMP) surgically treated and diagnosed by histopathology at Karolinska University Hospital 2006-2017 (Cohort A). A previously published cohort of 109 patients with follicular tumors was re-analyzed as well (Cohort B).

Results:

In Cohort A, patients with FTC had a higher Ki-67 index (p < 0.001), larger tumor size (p < 0.001) and higher age at diagnosis (p = 0.036) compared to patients with FTA or FT-UMP. Hürthle cell differentiation, present in 50 FTA, 20 FTC and 8 FT-UMP, was associated with higher Ki-67 index (p = 0.009). Multivariate analysis of Cohort A identified a high Ki-67 index (odds ratio [OR]: 1.215, p < 0.001) and large tumor size (OR: 1.038, p < 0.001) as independent predictors of FTC. Results remained consistent after exclusion of Hürthle cell tumors and in pooled analysis of Cohort A + B. The area under curve of the Ki-67 index for predicting FTC was 0.722 and a cut-off for Ki-67 index at above 5% resulted in a specificity at 93% and sensitivity at 31%. Subgroup analysis of FTCs in Cohort A showed an association of higher Ki-67 index to extrathyroidal extension (p = 0.001) as well as widely invasive subtype (p = 0.019) based on the WHO 2017 classification.

Conclusions

Pre-operative Ki-67 index may add diagnostic information for a subset of patients with follicular thyroid tumors.

https://ift.tt/2JpOysk

Medullary thyroid carcinoma: Application of Thyroid Imaging Reporting and Data System (TI-RADS) Classification

Abstract

Purpose

To evaluate the applicability of ultrasound (US)-based Thyroid Imaging Reporting and Data System (TI-RADS) for evaluating medullary thyroid carcinoma (MTC).

Materials and methods

US images and medical records of patients with cytopathology-confirmed MTC between June 2003 and November 2016 were retrospectively reviewed. Four independent reviewers (two experienced and two inexperienced radiologists) evaluated 57 pre-operative US images of patients with MTC for shape, composition, echogenicity, margin, calcification of the MTC nodules, and categorized the nodules using TI-RADS classification. Weighted Kappa statistics was used to determine the inter-observer agreement of TI-RADS. Univariate and multivariate analyses were performed to assess US findings associated with lymph node metastasis.

Results

Ninety-five percent of nodules were classified as either high suspicion (68%) or intermediate suspicion (26%). The overall inter-rater agreement was good (Kappa 0.84, agreement 91.52%), and inexperienced reviewers also showed good agreements with the most experienced reviewer (weighted Kappa 0.73 and 0.81). According to the univariate analysis, TI-RADS category 5, shape, microcalcification, and extrathyroid extension were significantly associated with lymph node metastasis in MTC patients (p = 0.003, 0.008, 0.001, and 0.021, respectively). As per the multivariate analysis, the presence of microcalcification and the irregular shape of the nodule were significantly associated with metastatic lymph nodes in MTC patients (odds ratio, 26.6; 95% CI, 2.7–263.7, p = 0.005, odds ratio, 14.7; 95% CI, 1.3–170, p = 0.031, respectively).

Conclusion

TI-RADS is applicable for the evaluation of MTC nodules with good inter-observer agreement.

https://ift.tt/2LjIWoB

Post-finasteride syndrome and post-SSRI sexual dysfunction: two sides of the same coin?

Abstract

Sexual dysfunction is a clinical condition due to different causes including the iatrogenic origin. For instance, it is well known that sexual dysfunction may occur in patients treated with antidepressants like selective serotonin reuptake inhibitors (SSRI). A similar side effect has been also reported during treatment with finasteride, an inhibitor of the enzyme 5alpha-reductase, for androgenetic alopecia. Interestingly, sexual dysfunction persists in both cases after drug discontinuation. These conditions have been named post-SSRI sexual dysfunction (PSSD) and post-finasteride syndrome (PFS). In particular, feeling of a lack of connection between the brain and penis, loss of libido and sex drive, difficulty in achieving an erection and genital paresthesia have been reported by patients of both conditions. It is interesting to note that the incidence of these diseases is probably so far underestimated and their etiopathogenesis is not sufficiently explored. To this aim, the present review will report the state of art of these two different pathologies and discuss, on the basis of the role exerted by three different neuromodulators such as dopamine, serotonin and neuroactive steroids, whether the persistent sexual dysfunction observed could be determined by common mechanisms.

https://ift.tt/2JpOp8g

Klinefelter syndrome, insulin resistance, metabolic syndrome, and diabetes: review of literature and clinical perspectives

Abstract

Purpose

Klinefelter syndrome (KS), the most frequent chromosomic abnormality in males, is associated with hypergonadotropic hypogonadism and an increased risk of cardiovascular diseases (CVD). The mechanisms involved in increasing risk of cardiovascular morbidity and mortality are not completely understood. This review summarises the current understandings of the complex relationship between KS, metabolic syndrome and cardiovascular risk in order to plan future studies and improve current strategies to reduce mortality in this high-risk population.

Methods

We searched PubMed, Web of Science, and Scopus for manuscripts published prior to November 2017 using key words "Klinefelter syndrome" AND "insulin resistance" OR "metabolic syndrome" OR "diabetes mellitus" OR "cardiovascular disease" OR "testosterone". Manuscripts were collated, studied and carried forward for discussion where appropriate.

Results

Insulin resistance, metabolic syndrome, and type 2 diabetes are more frequently diagnosed in KS than in the general population; however, the contribution of hypogonadism to metabolic derangement is highly controversial. Whether this dangerous combination of risk factors fully explains the CVD burden of KS patients remains unclear. In addition, testosterone replacement therapy only exerts a marginal action on the CVD system.

Conclusion

Since fat accumulation and distribution seem to play a relevant role in triggering metabolic abnormalities, an early diagnosis and a tailored intervention strategy with drugs aimed at targeting excessive visceral fat deposition appear necessary in patients with KS.

https://ift.tt/2L9GHnF

Gender-specific differences of interaction between cadmium exposure and obesity on prediabetes in the NHANES 2007–2012 population

Abstract

Purpose

Data from National Health and Nutrition Examination Survey (NHANES) for the years 2007–2012 were used to evaluate the interactions of cadmium (Cd) exposure with being overweight/obesity on the risk of prediabetes among adults 20 years older.

Methods

A total of 3552 subjects were included in the analysis. Urinary cadmium levels (UCd) was used as a biomarker for long-term exposure to Cd. Additive interaction was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (S).

Results

Following covariates adjustments, we found significant associations of UCd with higher prediabetes prevalence, and this association was more apparent in males (Q4 vs Q1: OR = 1.95, 95%CI: 1.34–2.84); while overweight/obesity was associated with prediabetes both in males and in females. Additionally, there was a significant interaction between Cd exposure and being overweight/obesity on prediabetes risk among males (RERI = 1.18, 95% CI: 0.42–1.93; AP = 0.35, 95% CI: 0.12–0.58; S = 2.00, 95% CI: 0.92–4.34).

Conclusions

Our results suggest that being overweight/obesity may substantially amplify the adverse effects of long-term cadmium exposure on prediabetes risk, and this interaction is more severe in male adults. Further studies are needed to confirm these findings.

https://ift.tt/2LjIrLf

Increasing soft tissue thickness does not affect trabecular bone score reproducibility: a phantom study

Abstract

Purpose

Trabecular Bone Score (TBS) provides an indirect score of trabecular microarchitecture from lumbar spine (LS) dual energy X-ray absorptiometry. Increasing soft tissue thickness artifactually reduces TBS values; we evaluated the effect of a fictitious increase of soft tissue thickness on TBS and bone mineral density (BMD) reproducibility on a phantom model.

Methods

A Hologic spine phantom was scanned with a QDR-Discovery W Hologic densitometer. Fresh pork rind layers of 5 mm were used to simulate the in-vivo soft tissues. For each scan mode (fast array [FA], array, high definition [HD]), 25 scans were consecutively performed without phantom repositioning, at 0 (no layers), 1 cm, 3 cm, and 6 cm of thickness. BMD and TBS reproducibility was calculated as the complement to 100% of least significant change.

Results

Both BMD and TBS reproducibility slightly decreased with increasing soft tissue; this difference was statistically significant only for BMD using HD modality (reproducibility decreased from 99.4% at baseline to 98.4% at 6-cm of thickness). TBS reproducibility was slightly lower compared to that of BMD, and ranged between 98.8% (array, 0 cm) and 97.4% (FA, 6 cm). Without taking into account manufacturer BMI optimization, we found a progressive decrease of TBS mean values with increasing soft tissue thickness. The highest TBS difference between baseline scan and 6 cm was −0.179 (−14.27%) using HD.

Conclusions

Despite being slightly lower than that of BMD, TBS reproducibility was not affected up to 6 cm of increasing soft tissue thickness, and was even less influenced by fat than BMD reproducibility.

https://ift.tt/2LiogtH

Molecular evaluation of a sporadic paraganglioma with concurrent IDH1 and ATRX mutations

Abstract

Purpose

Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors of neural crest origin. Germline or somatic mutations of numerous genes have been implicated in the pathogenesis of PPGLs, including the isocitrate dehydrogenase 1 (IDH1) gene and alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene. Although concurrent IDH1 and ATRX mutations are frequently seen in gliomas, they have never been reported together in PPGLs. The aim of this study was to characterize one paraganglioma with concurrent IDH1 and ATRX mutations identified by whole exome sequencing.

Methods

Leukocyte and tumor DNA were used for whole exome sequencing and Sanger sequencing. 2-hydroxyglurarate level and the global DNA methylation status in the tumor were measured. ATRX's cDNA transcripts were analyzed. Tyrosine hydroxylase (TH), HIF1α and ATRX staining, as well as telomere-specific FISH was also performed.

Results

The presence of a somatic IDH1 (c.394C>T, p.R132C) mutation and a concurrent somatic ATRX splicing mutation (c.4318-2A>G) in the current case was confirmed. Dramatic accumulation of 2-hydroxyglutarate was detected in the paraganglioma without the global DNA hypermethylation, and pseudohypoxia was also activated. Importantly, immunohistochemistry revealed negative TH staining in the tumor and the first exon region of TH gene was hypermethylated resulting in normal plasma metanephrines. The splicing ATRX mutation resulted in two transcripts, causing frameshifts. Immunohistochemistry revealed scarce ATRX staining in the tumor. Alternative lengthening of telomeres (ALT) was detected by FISH.

Conclusions

This case represents the first concurrence of IDH1 and ATRX mutations in PPGLs. Although relatively rare, a somatic R132C mutation of IDH1 might play a role in a small subset of sporadic PPGLs.

https://ift.tt/2LguSMr

Age at menarche and the risk of gestational diabetes mellitus: a systematic review and meta-analysis

Abstract

Purpose

Epidemiological studies had demonstrated that early age at menarche increased the risk of type 2 diabetes (T2DM), and gestational diabetes mellitus (GDM) shares many risk factors and features with T2DM. Thus, age at menarche may be a potential factor in the development of GDM. The aim of this study was to assess the association between age at menarche and the risk of gestational diabetes mellitus.

Methods

The databases of PubMed, Embase, Web of Science and Cochrane Library were searched up to June 2017.

Results

A total of 50,535 participants from five individual studies were included in the meta-analyses to evaluate the risk of GDM. Meta-analysis showed that women with menarche at an early age (≤11 years) had a higher GDM risk than those with menarche at age ≥12 years. (OR = 1.45, 95% CI = 1.26–1.68; P < .00001) There was low heterogeneity among the studies (Q = 6.4; P = 0.17; I^{2 =} 38).

Conclusions

This meta-analysis demonstrated that earlier menarche was strongly associated with an increased risk of GDM. A history of early age at menarche may help identify women at high risk of GDM and allow the implementation for the strategy of early prevention.

https://ift.tt/2LlckY4

Long-term effect of testosterone replacement therapy on bone in hypogonadal men with Klinefelter Syndrome

Abstract

Purpose

To assess different aspects of bone damage in untreated adult patients with Klinefelter Syndrome (KS) before and during testosterone replacement therapy (TRT).

Methods

Fifteen untreated hypogonadal men with KS and 26 control subjects (C) matched for age and BMI were recruited. Sex hormone levels were measured in all subjects. Lumbar spine (LS) and femoral (neck: FN and total hip: TH) bone mineral density (BMD), trabecular bone score (TBS), hip structure analysis (HSA) and fat measures (percentage of fat mass, android/gynoid ratio and visceral adipose tissue) were evaluated by DEXA. In KS patients, blood analysis and DEXA measurements were assessed at baseline and repeated yearly for three years during TRT.

Results

Fat measures were significantly higher in KS than C (p < 0.01). In contrast, mean LS, FN and TH BMD were significantly reduced in KS compared to C (p < 0.01), while there was no difference in TBS. HSA revealed a significantly lower cortical thickness and significantly higher buckling ratio in KS compared to C at all femoral sites (p < 0.01). In KS patients, TRT significantly increased BMD at LS only, but did not improve TBS and HSA parameters. Fat measures were inversely associated with TBS values, and TRT did not influence this relationship.

Conclusions

In untreated hypogonadal men with KS, lumbar and femoral BMD was reduced, and femoral bone quality was impaired. Adiposity seemed to have a detrimental effect on lumbar bone microarchitecture, as indirectly evaluated by TBS. However, TRT failed to remedy these negative effects on bone.

https://ift.tt/2uGkJ1o

Thyroid nodule ultrasound reports in routine clinical practice provide insufficient information to estimate risk of malignancy

Abstract

Purpose

Ultrasonographic characteristics of thyroid nodules play an important role in estimating the risk of malignancy (ROM). Guidelines mandate all thyroid nodules be characterized by six key ultrasonographic features to estimate the ROM. Our objective was to evaluate how frequently these characteristics were identified by radiologists and the ensuing utility to estimate ROM.

Methods

We retrospectively reviewed 1930 consecutive diagnostic thyroid ultrasound reports from a large community radiology practice. A total of 1339 individual patients were found to have one or more thyroid nodules. Each report was analyzed for six key ultrasonographic features. A utility score (UtS) was calculated (range 0–6) with a single point given for a comment on each feature.

Results

Of the 1339 patients, 75% of the studies reported more than one nodule (mean number of nodules = 3.4). Mean maximal diameter of the largest nodule per patient = 1.8 cm. The mean UtS was 2.57. Nodule size did not influence the UtS.: Nodule <1 cm (UtS: 2.53), 1–2 cm (UtS: 2.68) and >2 cm (UtS: 2.49). We believe a UtS of four or greater is needed to confidently estimate ROM: we found this in 13.7% of reports.

Conclusions

Our retrospective analysis of a large number of consecutive thyroid ultrasound reports in routine clinical practice suggests that the vast majority provide insufficient information to allow the clinician to risk stratify the nodules by estimating the ROM. This could lead to both over-diagnosis and over-treatment of benign/indolent thyroid lesions or under-diagnosis of clinically important thyroid cancers.

https://ift.tt/2uo3PFq

Treatment of multiresistant prolactinomas with a combination of cabergoline and octreotide LAR

Abstract

Background and objectives

Dopamine agonist (DA)-resistant prolactinomas are rare but they constitute a real challenge, since there are few therapeutic alternatives left for these patients.

Design and setting

Proof-of-concept study at a tertiary care, referral center.

Patients and methods

The studied population consisted of five patients (one female and four males, mean age at diagnosis 23.5 ± 19) with macroprolactinomas with persistent hyperprolactinemia and/or tumor mass despite high doses of cabergoline (CBG) and pituitary surgery, to whom 20 mg monthly of octreotide LAR was added for 6–13 months. Response was evaluated by measuring prolactin (PRL) levels and by magnetic resonance imaging. Immunohistochemistry (IHC) for pituitary hormones, Ki-67, and somatostatin receptor subtypes 2 and 5 was (SSTR2 and 5) was available in two of the subjects.

Results

The addition of octreotide LAR to ongoing CBG treatment had no effect on either PRL levels or tumor size in three patients. In two of the five patients, combination treatment resulted in a significant reduction in PRL concentrations (from 7643 to 200 ng/mL and from 2587 to 470 ng/mL) as well as in adenoma size (93% reduction). IHC evaluation of tumor samples from two patients (a responder and a non-responder) revealed positive immunostaining for PRL and SSTR5 but not for other pituitary hormones or for SSTR2.

Conclusions

The addition of a somatostatin analog to ongoing CBG treatment may be effective in some patients with DA-resistant macroprolactinomas, independently of the adenoma's SSTR expression profile.

https://ift.tt/2MjF8Rx

Is serum TSH a biomarker of thyroid carcinoma in patients residing in a mildly iodine-deficient area?

Abstract

Purpose

To investigate the association between the pre-operative serum TSH (s-TSH) level and differentiated thyroid carcinoma (DTC) in a mildly iodine-deficient area.

Methods

Patients undergoing surgery for thyroid nodular disease (TND) were included from three tertiary surgical departments. Data were collected from a national thyroid surgery database (THYKIR) and from patient charts. Individuals with overtly coexisting thyroid disorders were excluded for subgroup analyses. Patients were compared with the Danish background population, employing previous data from DanThyr, a study initiated to monitor the iodine fortification program in Denmark.

Results

Nine-hundred ninety-eight patients [cases/controls: 265/733; female/male: 794/204; age (mean ± SD): 51 ± 15 years] were included. S-TSH was significantly higher in the DTC group [median (IQR): 1.3 (0.9–1.9 mIU/L)] compared with the benign TND group [0.9 (0.6–1.5 mIU/L)] (p < 0.0001). The median s-TSH in the background population was similar to that found among DTC patients (p = 1.00), but markedly higher than the s-TSH level in the benign TND group (p < 0.0001). There was no association between s-TSH and DTC disease stage (p = 0.08–0.87).

Conclusions

s-TSH was significantly higher in patients with DTC than in those with benign TND. However, this difference can be explained by abnormally lower s-TSH level in the latter group, probably caused by subtle nodular functional autonomy. Due to the huge overlap and the small difference in median s-TSH between patients with benign and malignant TND, s-TSH is not suitable as a biomarker of DTC in a clinical setting.

https://ift.tt/2LoF81Q

Biomechanical properties of CAD/CAM-individualized nickel-titanium lingual retainers: an in vitro study

Abstract

Purpose

This study aimed to determine and compare the mechanical properties of novel CAD/CAM(computer-aided design/manufacturing)-individualized nickel-titanium (NiTi) and conventional twisted wires.

Methods

Seven NiTi wires (angular, 0.20 × 0.20 mm up to 0.50 × 0.50 mm) and two twisted steel wires (round, 0.40 mm and 0.44 mm) were investigated in three-point (3PBT) and four-point bending tests (4PBT) using the Orthodontic Measurement and Simulation System. All wires were loaded up to a distance of 3.3 mm, and resulting forces were measured. Additionally, in the biomechanical test (BMT), CAD/CAM-individualized NiTi retainers (0.35 × 0.35 mm) were subjected to intrusive and extrusive deformation of 0.1, 0.2, and 0.4 mm.

Results

For twisted wires, typical plastic deformations were found in 3PBT (0.40 mm: 0.3 mm; 0.44 mm: 0.4 mm), and maximum resulting forces for these reached 1.3 N and 3.2 N for the 0.40 mm and 0.44 mm wires, respectively. Corresponding values in the 4PBT totaled 0.8 N for the 0.40 mm and 1.9 N for the 0.44 mm twisted wire. The NiTi samples showed plastic deformations in the 3PBT for the 0.25 × 0.25 mm dimension and in 4PBT for the 0.35 mm × 0.35 mm version. At a deflection of 1.5 mm, both tests revealed significantly different forces for the NiTi wires of different dimensions (p ≤ 0.001). In the BMT, no remarkable loading plateau or plastic deformation was observed. The resulting forces were significantly higher for extrusive than for intrusive deformation (p ≤ 0.001).

Conclusions

Individualized NiTi retainers feature specific elasticity and dimensional stability, and more deflection is necessary to achieve permanent deformations. The CAD/CAM production process did not significantly influence the biomechanical properties of the NiTi wires.

https://ift.tt/2zJrzsv

In vitro biocompatibility of orthodontic miniscrews with human gingival fibroblast and SAOS-2 osteoblast cultures

Abstract

Purpose

Miniscrews are an important choice for orthodontic anchorage. Yet reports on failures do exist, and attempts have been made to elucidate the causes. Clinical outcomes may be compromised not only by the mechanical implications of miniscrew design and the location of anchorage but also by poor biocompatibility. Hence, this study deals with the surface roughness and elemental composition of miniscrews and how these properties may affect the in vitro biocompatibility of four commercially available miniscrews.

Methods

Most of the currently available miniscrews are made of TiAl6V4, an alloy widely considered to be biocompatible. The samples tested in this study included four similarly dimensioned TiAl6V4 products from different manufacturers: tomas® by Dentaurum, OrthoEasy® by Forestadent®, Dual Top™ by Jeil Medical/Promedia, and LOMAS by Mondeal®. The surface properties of these products were characterized by scanning electron microscopy (SEM) and energy-dispersive X‑ray spectroscopy (EDX). Cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and agar overlay assays according to ISO 10993-5.

Results

The miniscrew products were found to show variations in surface-finish quality pertaining to topography and chemical composition, with the latter departing slightly from the manufacturers' specifications. MTT assays yielded rates of cell culture viability in excess of 90%, and agar overlay assays did not reveal decoloration beyond the specimen outlines in any of the experimental groups tested.

Conclusions

The four miniscrew products exhibited some minor, but statistically significant, differences in microtopography, alloy composition, and biological inertness. Cytotoxicity testing revealed that all four products should be considered non-cytotoxic, thus, ruling out poor biocompatibility as a cause of miniscrew failure.

https://ift.tt/2mmduro

Biomechanical properties of CAD/CAM-individualized nickel-titanium lingual retainers: an in vitro study

Abstract

Purpose

This study aimed to determine and compare the mechanical properties of novel CAD/CAM(computer-aided design/manufacturing)-individualized nickel-titanium (NiTi) and conventional twisted wires.

Methods

Seven NiTi wires (angular, 0.20 × 0.20 mm up to 0.50 × 0.50 mm) and two twisted steel wires (round, 0.40 mm and 0.44 mm) were investigated in three-point (3PBT) and four-point bending tests (4PBT) using the Orthodontic Measurement and Simulation System. All wires were loaded up to a distance of 3.3 mm, and resulting forces were measured. Additionally, in the biomechanical test (BMT), CAD/CAM-individualized NiTi retainers (0.35 × 0.35 mm) were subjected to intrusive and extrusive deformation of 0.1, 0.2, and 0.4 mm.

Results

For twisted wires, typical plastic deformations were found in 3PBT (0.40 mm: 0.3 mm; 0.44 mm: 0.4 mm), and maximum resulting forces for these reached 1.3 N and 3.2 N for the 0.40 mm and 0.44 mm wires, respectively. Corresponding values in the 4PBT totaled 0.8 N for the 0.40 mm and 1.9 N for the 0.44 mm twisted wire. The NiTi samples showed plastic deformations in the 3PBT for the 0.25 × 0.25 mm dimension and in 4PBT for the 0.35 mm × 0.35 mm version. At a deflection of 1.5 mm, both tests revealed significantly different forces for the NiTi wires of different dimensions (p ≤ 0.001). In the BMT, no remarkable loading plateau or plastic deformation was observed. The resulting forces were significantly higher for extrusive than for intrusive deformation (p ≤ 0.001).

Conclusions

Individualized NiTi retainers feature specific elasticity and dimensional stability, and more deflection is necessary to achieve permanent deformations. The CAD/CAM production process did not significantly influence the biomechanical properties of the NiTi wires.

https://ift.tt/2zJrzsv

In vitro biocompatibility of orthodontic miniscrews with human gingival fibroblast and SAOS-2 osteoblast cultures

Abstract

Purpose

Miniscrews are an important choice for orthodontic anchorage. Yet reports on failures do exist, and attempts have been made to elucidate the causes. Clinical outcomes may be compromised not only by the mechanical implications of miniscrew design and the location of anchorage but also by poor biocompatibility. Hence, this study deals with the surface roughness and elemental composition of miniscrews and how these properties may affect the in vitro biocompatibility of four commercially available miniscrews.

Methods

Most of the currently available miniscrews are made of TiAl6V4, an alloy widely considered to be biocompatible. The samples tested in this study included four similarly dimensioned TiAl6V4 products from different manufacturers: tomas® by Dentaurum, OrthoEasy® by Forestadent®, Dual Top™ by Jeil Medical/Promedia, and LOMAS by Mondeal®. The surface properties of these products were characterized by scanning electron microscopy (SEM) and energy-dispersive X‑ray spectroscopy (EDX). Cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and agar overlay assays according to ISO 10993-5.

Results

The miniscrew products were found to show variations in surface-finish quality pertaining to topography and chemical composition, with the latter departing slightly from the manufacturers' specifications. MTT assays yielded rates of cell culture viability in excess of 90%, and agar overlay assays did not reveal decoloration beyond the specimen outlines in any of the experimental groups tested.

Conclusions

The four miniscrew products exhibited some minor, but statistically significant, differences in microtopography, alloy composition, and biological inertness. Cytotoxicity testing revealed that all four products should be considered non-cytotoxic, thus, ruling out poor biocompatibility as a cause of miniscrew failure.

https://ift.tt/2mmduro

Impact of Gender and Age on the Prognosis of Differentiated Thyroid Carcinoma: a Retrospective Analysis Based on SEER

Abstract

The incidence of thyroid cancer in females is significantly higher than that in males; however, females are more likely to have more favorable outcomes. We aimed to determine the characteristics of differentiated thyroid carcinoma (DTC) subtypes in males and females, and to compare their clinical behavior and survival. A total of 68,337 cases were recruited from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program. The disease-specific survival (DSS) of follicular variant papillary thyroid carcinoma (FVPTC) and follicular thyroid carcinoma (FTC) were similar to that of classical variant papillary thyroid carcinoma (CPTC) in male patients (FVPTC vs. CPTC, adjusted hazard ratio (aHR) = 0.947, P = 0.776; FTC vs. CPTC, aHR = 1.512, P = 0.104). In premenopausal female (< 55 years old), FVPTC had better DSS than CPTC (aHR = 0.321, P = 0.038) while FTC had worse DSS than CPTC (aHR = 3.272, P = 0.013); in postmenopausal female, FTC had poorer prognosis than CPTC (aHR = 2.145, P = 0.002), no statistical difference was found between CPTC and FVPTC (aHR = 0.724, P = 0.087). For patients younger than 55 years, women had significantly better DSS compared with men with CPTC (aHR = 0.376, P < 0.001) and FVPTC (aHR = 0.102, P < 0.001). However, no difference was observed in patients older than 55 years. Interestingly, outcomes of FTC were not affected by gender in patients of all ages. These results suggested that different clinical behaviors and outcomes of DTC subtypes should be considered in patients with different genders.

https://ift.tt/2NiKVXi

End-tidal carbon dioxide monitoring improves patient safety during propofol-based sedation for breast lumpectomy: A randomised controlled trial

BACKGROUND The use of sedation is becoming more commonplace. Although pulse oximetry is a standard monitoring procedure during sedation, it cannot accurately detect early hypoventilation. End-tidal carbon dioxide (EtCO2) monitoring can be an earlier indicator of airway compromise; however, the existing literature is limited to a few studies with varying outcomes. OBJECTIVES To evaluate whether EtCO2 monitoring decreases the incidences of CO2 retention and apnoeic events in propofol-based sedation. DESIGN Randomised controlled study. SETTING A tertiary hospital. PATIENTS Two hundred women (aged 18 to 65 years, ASA physical status 1 or 2) who were scheduled for breast lumpectomy between June 2017 and August 2017. INTERVENTIONS Patients were allocated randomly to receive either standard monitoring or standard monitoring and EtCO2 monitoring. MAIN OUTCOME MEASURES The primary outcome was the incidence of CO2 retention. The secondary outcomes were the number of actions taken to restore ventilation, variations in PaCO2 and pH, the frequency of apnoea and the recovery time. RESULTS CO2 retention occurred significantly less often in the EtCO2 monitoring group (10 vs. 87%; P 

https://ift.tt/2Nknqgq

Unfavorable Structural and Functional Outcomes in Myelin Oligodendrocyte Glycoprotein Antibody–Associated Optic Neuritis

Background: Recurrent optic neuritis (rON) associated with myelin oligodendrocyte glycoprotein (MOG)-specific antibodies has been initially reported to show a better clinical outcome than aquaporin-4 (AQP4)-seropositive ON in neuromyelitis optica spectrum disorder (NMOSD). Here, we characterize clinical and neuroimaging findings in severe cases of MOG antibody–positive and AQP4 antibody–negative bilateral rON. Methods: Three male adults with rON (ages 18, 44, and 63 years) were evaluated with optical coherence tomography (OCT), MRI, cerebrospinal fluid (CSF), and serological studies. Results: All patients experienced >7 relapses of ON with severe reduction of visual acuity and partial response to steroid treatment. Optic nerves were affected bilaterally, although unilateral relapses were more frequent than simultaneous bilateral recurrences. Patients were MOG-seropositive but repeatedly tested negative for AQP4 antibodies. OCT showed severe thinning of the peripapillary retinal nerve fiber layer. On MRI, contrast-enhancing lesions extended over more than half the length of the optic nerve. CSF analyses during ON episodes were normal. Severe visual deficits accumulated over time in 2 of 3 patients, despite immunosuppressive therapy. Conclusions: MOG-seropositive and AQP4-seronegative rON may be associated with an aggressive disease course and poor functional and structural outcomes. In contrast to previous reports, the severity and pattern of retinal and optic nerve damage closely resembled phenotypes commonly observed in AQP4-seropositive rON without fulfilling current diagnostic criteria for NMOSD. Address correspondence to Sven Schippling, MD, Neuroimmunology and Multiple Sclerosis Research Section, Department of Neurology, University Hospital Zurich, University of Zurich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland; E-mail: Sven.schippling@usz.ch. I. Jelcic, J. V. M. Hanson, K. Landau, R. Martin, A. Lutterotti, and S. Schippling are supported by the Clinical Research Priority Project Multiple Sclerosis (CRPPMS) of the University Zurich. S. Schippling and J. V. M. Hanson are supported by the Swiss MS Society. Before and subsequently to the conception and execution of the study, S. Lukas has been an employee of Heidelberg Engineering, Heidelberg, Germany. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (https://ift.tt/2BFTkP1). A. Lutterotti and S. Schippling are equally contributing authors. © 2018 by North American Neuro-Ophthalmology Society

https://ift.tt/2mlUdpW

The 44th Annual Meeting of the North American Neuro-Ophthalmology Society in Waikola Village on the Big Island, Hawaii 2018

No abstract available

https://ift.tt/2mlU6e0

Changes in esophageal mucosal morphology and in growth of breast feeding rats fed with milk of low or high temperature.

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Changes in esophageal mucosal morphology and in growth of breast feeding rats fed with milk of low or high temperature.

Hell J Nucl Med. 2018 Jul 12;:

Authors: Grammaticos PC, Emmanouil-Nikoloussie E, Trontzos C, Kaidoglou A, Foroglou C

Abstract
Dear Editor, This rather original investigation was performed some time ago but is still unpublished. Its aim was to estimate the effect of low or high temperature cow's milk given to breast feeding rats in order to study possible influence of this diet to rats, to their physical growth and also esophageal mucosal pathology. Ten white female Wistar rats, 20 days of age were separated from their mothers and divided in 2 groups of 5 members each. Five of them were fed with milk kept at 42oC by using a special warming device. The other 5 animals were fed with cold milk kept at 4oC during feeding. The duration of feeding was 34 days. Animals were finally sacrificed with a lethal dose of ether. The two groups were examined and compared. The group of rats fed by the warm milk was better grown as indicated by gaining more body weight, being more active and drinking more milk. Specimens were taken from the middle esophagus and after specific treatment were examined under the electronic microscope. We found: In both groups the most impressive finding in esophageal mucosa was an edematous intercellular space in all epithelial layers with many microorganisms in these layers. Acantholysis was often identified while in other areas a keratin transformation was noticed even in the basic layers, while basic membrane was absent. Epithelial cells showed edematous mitochondria and formation of myelin bodies. Degenerative changes and interstitial edema were noticed in the chorio. The above findings suggest that hot milk but not cold milk improves the growth of the rats studied. Cold and also hot milk had a damaging effect on the rats' esophageal mucosa. It is obvious that many options for further research arise related to the range of temperature of food intake that will not cause damage to gastric epithelium.

PMID: 30006651 [PubMed - as supplied by publisher]

https://ift.tt/2uJX7Jh

Erdheim-Chester disease diagnosed by 99mTc-MDP bone scintigraphy and brief literature review.

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Erdheim-Chester disease diagnosed by 99mTc-MDP bone scintigraphy and brief literature review.

Hell J Nucl Med. 2018 Jul 12;:

Authors: Şahin Ö, Oltulu P

Abstract
Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis with lipid-laden macrophages and fibrosis. Although ECD is a multisystemic disease, the most common finding is sclerotic bone involvement in the diametaphyseal regions of bilateral distal femur and in proximal and distal tibia. We present a 40 years old woman who for the last two years had various systemic symptoms, especially knee pain, polyuria and polydipsia. Although a "hot knee" pattern was seen in bone scintigraphy (BS), a femur biopsy was performed, due to the preliminary diagnosis of haematologic malignancy. The biopsy specimen showed only intense fibrosis. One year later while the patient was in our clinic, BS showed characteristic for ECD bone involvement. Bone biopsy specimens stained in hematoxylin and eosin showed dense fibrosis but not histiocytosis. However, after immunohistochemical staining with CD-68, histiocytes were discerned. In conclusion, the authors underline that ECD was diagnosed at a second diagnostic attempt both clinically and by specific staining pathology specimens.

PMID: 30006650 [PubMed - as supplied by publisher]

https://ift.tt/2mnSssy

Bone scan findings in erythromelalgia.

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Bone scan findings in erythromelalgia.

Hell J Nucl Med. 2018 Jul 12;:

Authors: Willekens I, Vandecasteele SJ, Verhoeven K, De Geeter F

Abstract
Erythromelalgia is a rare condition characterized by attacks of intensely painful, red and warm feet and/or hands. Symptoms typically are triggered by heat and relieved by cooling of the extremities. Primary cases are due to mutations in the gene for a sodium channel expressed in nociceptive and sympathetic ganglion neurons; secondary causes include blood disorders, infections, drugs, connective tissue diseases, neuropathic diseases, including diabetic neuropathy, and malignancies. We present bone scan findings in a case of erythromelalgia in an 18 years old student, in whom the symptoms developed suddenly. No underlying disease could be demonstrated and the patient fully recovered. The scan findings were strikingly similar to those of reflex sympathetic dystrophy.

PMID: 30006649 [PubMed - as supplied by publisher]

https://ift.tt/2zFGlQZ

Pituitary gland and bone involvement of Langerhans cell histiocytosis in a boy and brief review of the literature.

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Pituitary gland and bone involvement of Langerhans cell histiocytosis in a boy and brief review of the literature.

Hell J Nucl Med. 2018 Jul 12;:

Authors: Miao C, Zhang L, Sun M, Ma C

Abstract
A 3 years old boy was hospitalized with a month's history of polydipsia, polyuria and low fever. There was no relevant family history. This is a rare case of Langerhans cell histiocytosis (LCH) with both bone and pituitary infiltration shown on the technetium-99m methylene diphosphonate (99mTc-MDP) scan and brain magnetic resonance imaging (MRI). Sagittal and coronal T1-weighted images on MRI showed the typical lack of high signal intensity of the posterior pituitary which corresponded to the central signs of diabetes insipidus (DI). The diagnosis of LCH was suspected by 99mTc-MDP whole-body bone scan showing multiple bone lesions. The disease was further confirmed by pathology of the biopsy specimen from the right tibia. Brain MRI and bone scan are indicated for pediatric patients with DI. The high signal intensity of the posterior pituitary on MRI and the bone lytic lesions on scintigraphy suggested the diagnosis of LCH. This paper is original because it is the first full description of bone and pituitary involvement detected by bone scan and brain MRI in a pediatric LCH.

PMID: 30006648 [PubMed - as supplied by publisher]

https://ift.tt/2mnSals

More than the prostate: Intrapancreatic accessory spleen and papillary thyroid cancer detected with 18F-PSMA PET/CT.

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More than the prostate: Intrapancreatic accessory spleen and papillary thyroid cancer detected with 18F-PSMA PET/CT.

Hell J Nucl Med. 2018 Jul 12;:

Authors: Singh D, Horneman R, Nagra NK

Abstract
OBJECTIVE: Prostate specific membrane antigen (PSMA) positron emission tomography diagnostic computed tomography (PET/CT) is gaining an increasing role in the staging of prostate cancer and restaging in cases of biochemical recurrence. Our understanding of PSMA affinity for incidental pathological and non-pathological entities is also maturing although certain cases do present as diagnostic and management dilemmas.
SUBJECT AND METHODS: We present a case of a 55 years old man with prostate adenocarcinoma, with incidentally found pancreatic and thyroid lesions showing PSMA avidity.
RESULTS: We were able to utilize a heat damaged red blood cell single photon emission tomography (SPET)/CT scan and ultrasound guided fine needle aspiration (FNA) to accurately diagnose co-existent thyroid papillary carcinoma and intra-pancreatic accessory spleen (IPAS) tissue, respectively. The patient avoided invasive pancreatic tissue sampling and subsequent staging with fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT.
CONCLUSION: This is the first case to our knowledge describing both such lesions in one patient and the first case describing the use of 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL)-PSMA PET/CT to detect IPAS. Furthermore we highlight the value of nuclear medicine diagnostic work up in complex cases.

PMID: 30006647 [PubMed - as supplied by publisher]

https://ift.tt/2mkcwMt

Renal output efficiency and normalized residual activity examined by technetium-99m-DTPA renography have by far greater specificity to diagnose obstructive disease as compared to other conventional parameters of the renogram. First such study of output efficiency.

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Renal output efficiency and normalized residual activity examined by technetium-99m-DTPA renography have by far greater specificity to diagnose obstructive disease as compared to other conventional parameters of the renogram. First such study of output efficiency.

Hell J Nucl Med. 2018 Jul 12;:

Authors: Beatović SL, Radulović M, Janković MM, Artiko VM, Ajdinović B, Šobić-Šaranović DP

Abstract
OBJECTIVE: The aim of this study was to assess the diagnostic ability of renal output efficiency (OE), normalized residual activity (NORA) and conventional interpretation of the diethylene triamine pentaacetic acid (99mTc-DTPA) diuretic renogram (CIR) in diagnosing urine flow obstruction.
SUBJECTS AND METHODS: Group A consisted of 73 obstructed kidneys and Group B of 80 kidneys with dilated upper urinary tract. Forty eight kidneys were examined as the control Group C. A 40min acquisition with 240 of 10sec images was applied. Furosemide was administered after 20min (F+20). Post-void image was acquired at 50min. Output efficiency was calculated at 20min (OE20) and 20min after furosemide test (OE40) and NORA at 20min (NORA20) and on the post-micturition acquisition (NORAPM).
RESULTS: Both the above parameters (OE40 and NORAPM) had high sensitivity (92% and 97%), specificity (99% for both) and accuracy (95% and 98%) in differentiating between obstructed and dilated unobstructed kidneys. The test of NORAPM correctly reclassified 40 out of 41 indeterminate or false positive results of the conventional interpretations of renograms (CIR) as obstructed (12 cases) or dilated (28 cases). Cut-off values for obstruction were <80% and ≥0.23 for OE40 and NORAPM, respectively. Compared to CIR, both parameters showed better specificity, especially NORAPM.
CONCLUSION: Factors of OE40 and especially NORAPM of the renogram by 99mTc-DTPA were able to diagnose urine outflow obstruction better than CIR. Specifically, these factors well differentiated obstruction from urinary tract dilatation.

PMID: 30006646 [PubMed - as supplied by publisher]

https://ift.tt/2mjRoG0

Iodine-125 labeled Australian frog tree host-defense peptides caerin 1.1 and 1.9 better inhibit human breast cancer cells growth than the unlabeled peptides. 125I-caerin 1.9 may better be used for the treatment of breast cancer.

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Iodine-125 labeled Australian frog tree host-defense peptides caerin 1.1 and 1.9 better inhibit human breast cancer cells growth than the unlabeled peptides. 125I-caerin 1.9 may better be used for the treatment of breast cancer.

Hell J Nucl Med. 2018 Jul 12;:

Authors: Yuan J, You X, Ni G, Wang T, Cavezza S, Pan X, Liu X

Abstract
OBJECTIVE: We recently showed that host defense caerin peptides isolated from Australian frog tree were able to inhibit cervical cancer tumour cell growth in vitro. We wished to determine if radioactive isotope iodine-125 (125I) can be labeled to caerin 1.9 peptide and if this peptide is bioactive for breast cancer cells treatment.
SUBJECTS AND METHODS: The biological function of caerin (1.1 and 1.9) peptides were investigated by in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay. The anti-cancer effect of 125I labeled caerin 1.9 was compared with unlabeled caerin 1.9 peptide. The tissue distribution of 125I labeled caerin 1.9 peptide was further studied in mice.
RESULTS: In the current paper, we demonstrated that caerin peptides (1.1 and 1.9) were separately able to inhibit the viability of two breast cancer cell lines in vitro and this inhibition was more profound when these peptides were simultaneously applied. Moreover, 125I can be stably attached to caerin 1.9 peptide with high efficiency. Iodine-125 labeled caerin 1.9 inhibited breast cancer cells line MCF-7 viability more efficiently than free 125I and also than unlabeled caerin 1.9. Additionally, iodine-125 labeled caerin 1.9 in vivo imaging demonstrated that although slightly, it could be accumulated in tumor tissue.
CONCLUSION: Our results from this totally original study indicated that radioactive isotope 125I labeled to caerin peptide 1.9 may be used to treat breast cancer while at the same time the response to treatment may be monitored by simultaneous imaging.

PMID: 30006645 [PubMed - as supplied by publisher]

https://ift.tt/2zGTgST

More accurate than MRI measurement of tumor size in breast cancer by using the peri-tumoral halo uptake layer method of the 18F-FDG PET/CT scan.

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More accurate than MRI measurement of tumor size in breast cancer by using the peri-tumoral halo uptake layer method of the 18F-FDG PET/CT scan.

Hell J Nucl Med. 2018 Jul 12;:

Authors: Park SH, Seo M, Choi HJ, Bae K, Bang M, Jun S

Abstract
OBJECTIVE: To evaluate the reliability of a method using the peri-tumoral halo layer (PHL) for assessing tumor size in breast cancer patients on the fluorine-18-fluorodeoxy glucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan compared to MRI and pathology.
SUBJECTS AND METHODS: Among 121 patients with breast cancer who underwent both 18F-FDG PET/CT and MRI between March 2013 and June 2016, 59 patients were included in this study. Exclusion criteria were as follows: history of neoadjuvant therapy, history of pre-operative mammotome, insufficient pathologic/radiologic size report, clustered tumor, positive tumor resection margin, 18F-FDG non-avid tumor. The PHL was examined by two nuclear medicine physicians. Tumor sizes (longest diameters) on 18F-FDG PET/CT were estimated using margins defined as the inner line of the PHL. Pathologic tumor sizes were utilized as reference standards.
RESULTS: The PHL of each tumor was most commonly designated as the 20%-30% band of the maximum standardized uptake value (SUVmax) it exhibited an inverse correlation with tumor SUVmax. Tumor size on 18F-FDG PET/CT showed a more linear correlation with pathology than that on MRI (r2=0.91 vs 0.65). In Bland-Altman analysis, 18F-FDG PET/CT showed significantly lower bias in size difference relative to pathology, compared with MRI (0.6±9.6cm vs. -1.9±17.3cm). Fluorine-18-FDG PET/CT showed more accurate T staging with pathology, especially in T3 cases, than MRI.
CONCLUSION: A method of tumor size determination, using PHL on 18F-FDG PET/CT, showed more linear relationship and smaller size differences with pathology than MRI (average 0.6 vs. 1.9cm). It provides sufficient reliability and reproducibility for measuring tumor size in breast cancer.

PMID: 30006644 [PubMed - as supplied by publisher]

https://ift.tt/2mkA7MP