Head and Neck Diseases by Alexandros G.Sfakianakis: 02/05/18

Δευτέρα 5 Φεβρουαρίου 2018

Development and Validation of the Mastocytosis Activity Score: MAS

Abstract

Background

Mastocytosis is a heterogeneous disease characterized by a clonal expansion of mast cells in various organs. The vast majority of patients suffer from signs and symptoms caused by mediator release from mast cells. Although the disease burden is high, there is currently no specific and validated instrument to measure and monitor signs and symptoms in patients with mastocytosis.

Objective

To develop and validate a disease-specific tool to measure and monitor the activity of signs and symptoms in patients with mastocytosis, the Mastocytosis Activity Score (MAS).

Methods

Nineteen potential MAS items were developed in a combined approach consisting of semi-structured patient interviews, expert input, and literature research. Item selection was performed by impact analysis with 76 patients followed by a review for face validity. The resulting MAS was tested for validity, reliability and influence factors. In parallel, a US American-English version of the MAS was developed.

Results

68 mastocytosis patients took part in the MAS validation study. The final 9-item MAS was found to have a three-domain structure ('skin', 'gastrointestinal tract', 'other'), a valid total score and an excellent test-retest-reliability. Multiple regression analysis revealed that disease duration, age, or gender are no significant determinant of the MAS results.

Conclusions

The MAS is a disease-specific, valid and reliable patient reported outcome measure for adult patients with cutaneous and indolent systemic mastocytosis. It may serve as a valuable tool to measure and monitor mastocytosis activity, both, in clinical trials and in routine care.

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Repeated restraint stress reduces the acquisition and relapse of methamphetamine-conditioned place preference but not behavioral sensitization

Publication date: Available online 5 February 2018
Source:Brain Research Bulletin
Author(s): Jee-Yeon Seo, Yong-Hyun Ko, Shi-Xun Ma, Bo-Ram Lee, Seok-Yong Lee, Choon-Gon Jang
The studies for the effects of stress on drug addiction were mostly obtained using sequential exposure to stress and drugs. However, few studies have been conducted on the effects of simultaneous exposure to stress and methamphetamine (METH) on METH-induced reward effects and behavioral sensitization. Thus, we examined the effects of simultaneous exposure to restraint stress and METH on METH-induced addictive behaviors using conditioned place preference (CPP) in mice. During the conditioning period, the mice were exposed to 2 h restraint stress before administration of METH or saline for 4 days. To investigate the effect of restraint stress on drug relapse, the mice were exposed to 2 h of restraint stress for 4 days during the late period of withdrawal. The results showed that the acquisition of METH CPP was impaired by simultaneous exposure to restraint stress and METH administration and the impairment of METH CPP was retained until METH-induced reinstatement. Additionally, based on locomotor activity data measured during METH reinstatement, simultaneous stress exposure during the conditioning phase increased METH-induced locomotor sensitization. We also found that the magnitude of METH-primed relapse was reduced in mice exposed to restraint stress during the late period of withdrawal. Taken together, these findings suggest that simultaneous exposure to restraint stress and METH can reduce the acquisition and relapse of METH-induced addictive behaviors but not behavioral sensitization.

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Involvement of NO/NMDA-R pathway in the behavioral despair induced by amphetamine withdrawal

Publication date: Available online 5 February 2018
Source:Brain Research Bulletin
Author(s): Arvin Haj-Mirzaian, Shayan Amiri, Hossein Amini-Khoei, Arya Haj-Mirzaian, Arsalan Hashemiaghdam, Kiana Ramezanzadeh, Maria Ghesmati, Khashayar Afshari, Ahmad Reza Dehpour
Abrupt discontinuation of chronic amphetamine consumption leads to withdrawal symptoms including depression, anhedonia, dysphoria, fatigue, and anxiety. These irritating symptoms may result in continuing to take the drug or can lead to suicidal behavior. Past studies have shown the involvement of various biologic systems in depression induced following amphetamine withdrawal (AW). However, there is no evidence about the relation between nitric oxide (NO) with NMDA receptors on depression following AW. In this study, we examined the involvement of the NO/NMDA pathways on depressive-like behaviors after 24 h withdrawal following 5 continuous days of amphetamine administration in male NMRI mice. Behavioral tasks used for depression assessment included the forced swimming test (FST), the Splash test and the open field test (OFT). In order to evaluate the role of NO/NMDA pathways animals treated with MK-801 (NMDA-R antagonist), Aminoguanidine (AG), a selective iNOS inhibitor, Nω-Nitro-L-arginine (L-NNA), a non-selective NOS inhibitor and 7-Nitro indazole (7-NI), a selective nNOS inhibitor. We also measured the level of nitrite in the hippocampus. Our data showed that AW induced the depressive-like effect in the FST and the Splash test. We showed that administration of AG, L-NNA, and MK-801 mitigated AW induced depression, however, 7-NI was failed to decrease depressive-like behaviors. Also, the antidepressant-like effect of co-injection of sub-effective doses of MK-801 with AG suggested that inducible nitric oxide synthase (iNOS) is associated with NMDA-R in AW induced depression. In conclusion, both NO and NMDA-R pathways are involved and related to each other in depression induced following AW.

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Effect of glucagon-like peptide-1 analogue; Exendin-4, on cognitive functions in type 2 diabetes mellitus; possible modulation of brain derived neurotrophic factor and brain Visfatin

Publication date: Available online 5 February 2018
Source:Brain Research Bulletin
Author(s): O.M. Abdelwahed, O.M. Tork, M.M. Gamal el Din, L. Rashed, M. Zickri
BackgroundBrain derived neurotrophic factor (BDNF) is one of the most essential neurotrophic factors in the brain. BDNF is involved in learning, memory and locomotion suggesting it as a target in type 2 diabetes mellitus (T2DM) associated cognitive changes. Visfatin; an adipokine discovered to be expressed in the brain; was found to have multiple effects including its participation in keeping energy supply to the cell and is consequentially involved in cell survival. Its role in cognitive functions in T2DM was not studied before. Recent studies point to the possible neuro-protective mechanisms of glucagon-like peptide 1 analogue: Exendin-4 (Ex-4) in many cognitive disorders, but whether BDNF or Visfatin are involved or not in its neuro-protective mechanisms; is still unknown.Aimsto study the changes in cognitive functions in T2DM, either not treated or treated with Glucagon-like peptide 1 (GLP-1) analogue: Ex-4, and to identify the possible underlying mechanisms of these changes and whether BDNF and brain Visfatin are involved.MethodsA total of 36 adult male wistar albino rats were divided into 4 groups; Control, Exendin-4 control, Diabetic and Exendin-4 treated groups. At the end of the study, Y-maze and open field tests were done the day before scarification to assess spatial working memory and locomotion, respectively. Fasting glucose and insulin, lipid profile and tumor necrosis factor- alpha (TNF-α) were measured in the serum. Homeostasis model assessment insulin resistance was calculated. In the brain tissue, malondialdehyde (MDA) level, gene expression and protein levels of BDNF and Visfatin, area of degenerated neurons, area of glial cells and area % of synaptophysin immunoexpression were assessed.ResultsCompared with the control, the untreated diabetic rats showed insulin resistance, dyslipidemia and elevation of serum TNF-α. The brain tissue showed down-regulation of BDNF gene expression and reduction of its protein level, up-regulation of Visfatin gene expression and elevation of its protein level, increase in MDA, area of degenerated neurons and area of glial cells and reduction in area % of synaptophysin immunoexpression. These changes were paralleled with significant deterioration in spatial working memory and locomotion. Treatment of diabetic rats with Ex-4 reversed all these changes.ConclusionT2DM has a negative impact on cognitive functions through different pathological and subcellular mechanisms. The current study provides evidence for involvement of BDNF and brain Visfatin in T2DM- associated cognitive dysfunction. BDNF and brain Visfatin were also found to contribute to the neuro-protective effect of Ex-4 via modulation of inflammation, oxidative stress, neuro-degeneration and synaptic function.

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Baseline neutrophil to lymphocyte ratio combined with serum LDH level associated with outcome of nivolumab immunotherapy in a Japanese advanced melanoma population

Abstract

Although immune checkpoint inhibitors (ICI) significantly improve the survival of advanced melanoma, more than half of the patients received no benefit. To predict outcomes, efforts to associate baseline peripheral blood biomarkers were started in patients given treatment with ipilimumab. Among the most critical markers is an increased neutrophil-to-lymphocyte ratio (NLR), which negatively correlates with outcome. Although several baseline factors have been reported to correlate with outcome in patients treated with nivolumab/pembrolizumab (eosinophil count, lymphocyte count, lactate dehydrogenase [LDH], and c-reactive protein [CRP]), a positive link between NLR and outcome has yet to be shown.

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Wide skin markings pattern - melanoma descriptor or patient-related factor?

Abstract

We are intrigued by the findings reported in the letter titled "Uncovering the diagnostic dermoscopic features of flat melanomas located on the lower limbs"(1). Bassoli et al investigated the association of the "wider skin marking pattern" with cutaneous melanoma. They state that this feature corresponds to "…linear intercepting furrows, lighter than the lesion's overall pigmentation and wider compared to the surrounding skin. The authors conclude that "recognition of wider skin markings may…prompt the clinician to obtain a biopsy specimen." We respectfully ask the authors to clarify several aspects of their study methodology.

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Application of in vivo reflectance confocal microscopy (RCM) and ex vivo fluorescence confocal microscopy (FCM) in most common subtypes of Basal Cell Carcinoma and correlation with histopathology

Abstract

Basal cell carcinoma (BCC) accounts for 80% of non-melanoma skin cancer. The identification of the histological subtype is crucial for the correct management of the tumor. In vivo reflectance confocal microscopy (RCM) is a novel technique that has demonstrated high sensitivity and specificity in the in vivo diagnosis of BCC. In an effort to determine reliable criteria for preoperative diagnosis of BCC subtypes, Longo et al. and Peppelman et al., described RCM criteria present in different BCC subtypes.

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Hyaluronan metabolism enhanced during epidermal differentiation is suppressed by vitamin C

Abstract

Background

Hyaluronan is a large, linear glycosaminoglycan present throughout the narrow extracellular space of the vital epidermis. Increased hyaluronan metabolism takes place in epidermal hypertrophy, wound healing and cancer. Hyaluronan is produced by hyaluronan synthases (HAS1-3) and catabolized by hyaluronidases (HYAL1 and -2), reactive oxygen species (ROS), and the KIAA1199 protein.

Objectives

To investigate the changes in hyaluronan metabolism during epidermal stratification and maturation, and the impact of vitamin C.

Methods

Hyaluronan synthesis and expression of the hyaluronan-related genes were analyzed during epidermal maturation from a simple epithelium to a fully differentiated epidermis in organotypic cultures of rat epidermal keratinocytes (REK) using qRT-PCR, immunostainings, and western blotting, in the presence and absence of vitamin C.

Results

With epidermal stratification, both the production and the degradation of hyaluronan were enhanced, resulting in an increase of hyaluronan fragments of various sizes. While the mRNA levels of Has3 and KIAA1199 remained stable during the maturation, Has1, Has2, and Hyal2 showed a transient upregulation during stratification, Hyal1 remained permanently increased, and the hyaluronan receptor Cd44 decreased. At maturation, Vitamin C downregulated Has2, Hyal2 and Cd44, while it increased high molecular mass hyaluronan in the epidermis, and reduced small fragments in the medium, suggesting stabilization of epidermal hyaluronan.

Conclusions

Epidermal stratification and maturation is associated with enhanced hyaluronan turnover, and release of large amounts of hyaluronan fragments. The high turnover is suppressed by vitamin C, which is suggested to enhance normal epidermal differentiation in part through its effect on hyaluronan.

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Levocarnitine for vismodegib-associated muscle spasms: a pilot randomized, double-blind, placebo-controlled, investigator initiated trial

Abstract

Smoothened inhibitors (SIs) are a new, targeted therapy for the treatment of advanced basal cell carcinoma (BCC), but their usage is significantly limited by the most common side effect, muscle spasms. Muscle spasms affect up to 80% of users, and are the most common reason for drug discontinuation despite tumor response. Currently, no placebo-controlled trials exist to guide the management of vismodegib-related muscle spasms. The medical literature suggests that the naturally occurring substance, levocarnitine (LC), can improve contractile function of muscle and reduce markers of exercise-induced stress. Hence, we explored the effect of oral LC on vismodegib-related muscle spasms via a double-blind, randomized, placebo-controlled, two-period crossover design.

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Factors associated with delayed referral for infantile hemangioma necessitating propranolol

Abstract

Background

Oral propranolol is the gold-standard to treat infantile hemangiomas. There is better efficacy and a lower risk of sequelae if therapy is started before the end of the growth phase, but most children are referred too late. Herein, we report the first study to investigate the delay and its associated factors when referring infants with infantile hemangiomas that need propranolol therapy.

Objectives

The primary objective was to determine the delay in referral (time between age at referral [first phone contact] and the optimal age for referral (fixed at 75 days). The second objective was to determine the impact of weighted factors associated with delayed referral assessed by logistic regression performed on two subgroups (referral <75 vs. >75 days).

Methods

Monocentric, retrospective, observational study included infants with infantile hemangiomas treated with oral propranolol between August 2014 and May 2017.

Results

82 children (83% females) were included. Before referral, 81 (99%) children had seen another physician (a pediatrician in 67% of cases). Median age at referral was 99 [2-478] days and 63% phoned after 75 days. Median age at the first visit was 111 days [2-515] and median age when propranolol was started was 128 days [32-541]. After adjustment, in multivariate analyses, location on the lips (OR (CI_95%): 4.21[1.19–14.89]) and superficial hemangioma (OR (CI_95%): 4.19 [1.55–11.34]) emerged as the most significant factors to influence referral before 75 days.

Conclusions

This study adds to our understanding regarding delayed referral and has identified targets for future information campaigns.

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Comparison of fungal fluorescent staining and ITS rDNA PCR-based sequencing with conventional methods for the diagnosis of onychomycosis

Abstract

Background

The current gold standard for diagnosing onychomycosis is direct microscopic examination and culturing. Fungal culture is a time-consuming procedure, while direct microscopy of potassium hydroxide (KOH) mounts suffers from low sensitivity. More rapid and sensitive methods for the diagnosis of onychomycosis are in high demand.

Objective

To establish an effective method for the diagnosis of onchomycosis by assessing the efficacies of fungal fluorescent staining and internal transcribed spacer (ITS) ribosomal DNA (rDNA) polymerase chain reaction (PCR)-based sequencing.

Methods

A total of 204 clinical specimens from patients with suspected onychomycosis were analysed. The gold standard for a true positive sample was positive by KOH, culturing, or both methods. All specimens were also tested by fungal fluorescent staining and its rDNA PCR-based sequencing. We compared the detection, sensitivity, and specificity for these two methods with conventional methods.

Results

In total, 126 (62%) and 102 (50%) were detected by fluorescent staining and PCR-based sequencing, respectively. According to the conventional diagnostic standard, the sensitivity of fluorescent staining and PCR-based sequencing was 97% and 78%, respectively, and specificities of 89% and 90%, respectively. Use of fluorescence enhanced the sensitivity of direct examination by 12% compared with KOH. PCR-based sequencing increased the sensitivity by 6% compared with culturing.

Conclusions

Fluorescence microscopy has a higher sensitivity for the detection of fungi in nail specimens compared with KOH and can be used as a rapid screening tool. PCR-based sequencing was faster and more sensitive compared with culture and when used in conjunction with fluorescence microscopy resulted in higher efficiency.

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Molecular genetic analyses of human endogenous retroviral elements belonging to the HERV-P and -R family in Primary Cutaneous T-Cell Lymphomas

Abstract

Mycosis fungoides (MF) is characterized by longstanding, scaly patch lesions preferentially involving the buttocks and body areas infrequently exposed to sunlight and by a slow evolution over years from patches to plaques and eventually tumors or erythroderma. Lymph node and visceral involvement, as well as large cell transformation, frequently occur in the late stages of the disease [1]. Sézary syndrome (SS) is an erythrodermic cutaneous T-cell lymphoma (CTCL) with leukemic involvement, an aggressive clinical behavior and poor prognosis [2].

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Studying the effect of systemic and biological drugs on intima-media thickness in patients suffering from moderate and severe psoriasis

Abstract

Background

Psoriasis has been related to a large number of cardiovascular risk factors such as hypertension, diabetes mellitus and arteriosclerosis. The increased carotid intima-media thickness (IMT) could be considered to be a marker of generalized arteriosclerosis.

Objective

To assess the effect of systemic and biological drugs on psoriatic patients′ carotid IMT.

Methods

A prospective study was performed. We studied 53 patients with moderate and severe psoriasis from our psoriasis dermatological unit, analyzing lipid and glucose metabolism and performing a carotid IMT sonography before introduction of systemic and biological drugs. After that, we performed an 8-month closely analytic and sonographic follow-up.

Results

The IMT of the psoriatic patients treated with biological drugs tended to decrease, although this occurrence was not statistically significant (p=0.086). The subgroup analysis revealed that patients treated with Methotrexate (p=0,045) and Anti Il-12/23 (p=0,010) presented a decrease of their IMT levels. This analysis also showed a decrease in glycaemia and insulin levels in patients treated with TNF-alpha Inhibitors and Ustekinumab.

Conclusions

Our study suggest that the carotid-IMT may benefits from treatment with biological drugs, particularly Anti IL-12/23, and methotrexate in patients suffering from moderate and severe psoriasis. However, larger longitudinal studies should be performed in order to fully confirm these results.

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Use of Medical Photography Among Dermatologists: A Nationwide Online Survey Study

Abstract

Background

Medical photography enhances patient care, medical education, and research. Despite medical photography's widespread use, little is known about how dermatologists choose to implement photography in routine clinical practice, and how they approach issues of image storage, image security, and patient consent.

Objective

To characterize dermatologists' medical photography habits and opinions.

Methods

A 32-item anonymous, multiple-choice SurveyMonkey questionnaire about medical photography practices was emailed to program directors of the 117 United States (US) dermatology residency programs between May and August 2015, with a request to forward to faculty and affiliated dermatologists. Only board-certified dermatologists practicing in the US were eligible. The Institutional Review Board exempted our study from full review.

Results

Our survey included 153 board-certified dermatologists, primarily representing the northeast (43.1%) and identifying as academic dermatologists (75.5%). Medical photography is prevalent: 61.8% report everyday use and 21.7% photograph every patient. Those reporting rare use (3.3%) were, on average, 20 years older. Dermatologists most commonly use photography to mark biopsy sites (87.5%), track disease (82.9%), and for education/teaching (72.4%). Nearly half (46%) use smartphone cameras. Emailing and texting photographs with patients or colleagues are common (69.1%). Most dermatologists (75.7%) always request patient consent for photographs. Only 23.7% adhere to a photography protocol and 73.9% desire more training opportunities.

Conclusion

Dermatologists value medical photography. While patterns of image acquisition, storage, and consent are noted, a variety of methods and preferences exist. Clearer photography guidelines and increased educational resources are likely to improve image quality, exchangeability, and confidentiality.

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Baseline neutrophil to lymphocyte ratio combined with serum LDH level associated with outcome of nivolumab immunotherapy in a Japanese advanced melanoma population

Abstract

http://ift.tt/2BYmMiM

Wide skin markings pattern - melanoma descriptor or patient-related factor?

Abstract

http://ift.tt/2nH7r1F

Application of in vivo reflectance confocal microscopy (RCM) and ex vivo fluorescence confocal microscopy (FCM) in most common subtypes of Basal Cell Carcinoma and correlation with histopathology

Abstract

http://ift.tt/2BYmCrG

Hyaluronan metabolism enhanced during epidermal differentiation is suppressed by vitamin C

Abstract

Background

Objectives

To investigate the changes in hyaluronan metabolism during epidermal stratification and maturation, and the impact of vitamin C.

Methods

Results

Conclusions

http://ift.tt/2nH7sTh

Impact of long-term fertilization practices on the soil aggregation and humic substances under double-cropped rice fields

Abstract

Soil organic matter (SOM) content and soil aggregation are essential components of soil structure, which plays an important role in soil quality and fertility. Also, the SOM content, aggregation, and humus substances in paddy field were affected by application of fertilization practices. However, there is still limited information about the effects of long-term different fertilization practices on soil aggregation and carbon content in the humic acid (C-HAF), fulvic acid (C-FAF), and humin (C-HUM) fractions under double-cropping rice (Oryza sativa L.) system in Southern China paddy fields. Therefore, the effects of long-term fertilizer application on soil aggregation and C-HUM, C-HAF, and C-FAF contents in 0–5-, 5–10-, and 10–20-cm soil depth under double-cropped rice fields in Southern China were investigated. The experiment located at NingXiang County in Hunan Province, China begins in 1986 and the experiment includes five treatments: without fertilizer input (CK), mineral fertilizer alone (MF), rice straw residues and mineral fertilizer (RF), 30% organic matter and 70% mineral fertilizer (LOM), and 60% organic matter and 40% mineral fertilizer (HOM). The results showed that the soil total organic carbon content in paddy soils with RF, LOM, and HOM treatments was significant higher (P < 0.05) than that of the CK treatment at early and late rice maturity stages. The different sizes of soil aggregates with different fertilization treatments were decreased as HOM > LOM > RF > MF > CK. The HOM treatment had the highest percentage of soil aggregates in each size class and the CK treatment had the lowest percentage of soil aggregates in each size class in 0–5-, 5–10-, and 10–20-cm soil depth at early and late rice maturity stages. The soil C-HAF, C-FAF, and C-HUM contents were increased by long-term combined application of manure with mineral fertilizer practices. Meanwhile, the results indicated that the soil C-HAF, C-FAF, and C-HUM contents with RF, LOM, and HOM treatments were significantly higher (P < 0.05) than that of the CK treatment at early and late rice maturity stages. As a result, the soil total organic carbon content, each size class of soil aggregates, and soil C-HAF, C-FAF, and C-HUM contents were increased by long-term combined application of manure with mineral fertilizer in double-cropped rice fields.

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Label-free imaging for T staging of gastric carcinoma by multiphoton microscopy

Abstract

Gastric cancer is one of the most common malignancies worldwide. The accurate diagnosis of tumor invasion depth is critical for therapeutic strategy and prognosis. Without fluorescent labelling, multiphoton microscopy (MPM) imaging could directly reveal tissue architecture based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). In this study, we aimed to explore the feasibility of MPM imaging to assess the gastric tumor morphology and infiltration. Unstained slides of 18 fresh gastric tissues with different T staging were examined by multiphoton microscopy. Morphological and quantitative analyses were both conducted. The nuclear area was defined as the area of nuclear boundary. Collagen content was defined as the ratio of SHG pixels to all pixels. Gastric normal and tumor tissues under different T stages visually presented with cellular and subcellular features on fluorescent imaging. The nuclear areas of normal and cancerous cells were 32.01 ± 2.89 and 58.41 ± 6.06 μm² (P < 0.001), respectively. Collagen content was quantified as 0.087 ± 0.012 in normal mucosa but 0.020 ± 0.007 in cancerous mucosa (P < 0.001). All results were in accord with the paired H&E-stained slides. Our findings suggested the convincing potential of MPM for judging T staging of gastric cancer. Without staining intervention, TPEF and SHG of MPM imaging could objectively and quantitatively indicate the subcellular and molecular changes during carcinogenesis. With the advancement of deep penetration, self-focus imaging and three-dimensional (3D) visualization, label-free MPM imaging compacted with endoscopy could be further introduced to realize the real-time in vivo assessment of tumor invasion clinically.

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Age-related differences in the functional properties of lips compared with skin

Abstract

Background/aims

Lips can easily become dry and rough and their biggest problems are drying and chapping. The cause of those problems is considered to be that the stratum corneum (SC) moisture is small and its barrier function is low. However, those problems decrease in subjects as they approach 40 years of age, after which problems due to their shape and color increase. The purpose of this study was to investigate relationships between SC properties of the lips during aging and to clarify the cause(s) of lip problems.

Methods

One hundred and 38 Japanese female subjects with normal skin ranging in age from 16 to 78 years were enrolled in the study. The capacitance and transepidermal water loss (TEWL) values, viscoelasticity, and color of their lips were measured and compared with their cheeks.

Results

The capacitance values for the lip and the cheek increased and TEWL values for both areas decreased with age. TEWL values for the lip decreased until ~30 years of age and this is considered to be related to the problem of drying. Although the maximum amplitude U_f of the lip increased with age, the U_r/U_f had no correlation with age. As for color, the L* and a* values decreased with age.

Conclusion

Age-related changes with regard to SC functions, viscoelasticity and color of the lips have been clarified for the first time, and it is clear that these changes are related to problems of the lips. Compared with the cheeks, differences with the lips are more apparent.

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Non-invasive evaluation of human mucosal structures by multiphoton laser scanning tomography in vitro

Abstract

Background

Mucous membranes may be affected by various diseases and the diagnostic accessibility is limited. Multiphoton laser tomography (MPT) is a useful tool for in vivo evaluation of superficial skin structures and might also be useful for the imaging of mucosa.

Objectives

In order to investigate the suitability of MPT for the evaluation of mucous membranes, tissue samples of different donors and anatomical localizations have been imaged.

Methods

Human mucosa samples from the urinary bladder, palatine tonsil and ocular conjunctiva were investigated by MPT and subsequently compared with conventional histology.

Results

Horizontal images of the epithelium and the underlying connective tissue were obtained using the autofluorescence and second harmonics generation signals by MPT. The stratification of multilayered epithelium was consistently reproduced. Also inflammatory changes like lymphocytic infiltrates and widened intercellular spaces were imaged in some cases.

Conclusion

Mucous tissue samples were obtained and MPT imaging was successfully performed. In the direct comparison with histology of the same tissue samples, the characteristic morphology of the epithelia was found. Further studies are necessary in order to compare images of healthy and diseased mucosal epithelium and the use of MPT for its evaluation in vivo.

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Plasma exeresis for active acne vulgaris: Clinical and in vivo microscopic documentation of treatment efficacy by means of reflectance confocal microscopy

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Herpes zoster at the vaccination site in immunized healthy children

Abstract

In this case series, we report seven immunized healthy children without underlying immunodeficiency who presented with herpes zoster that correlated with varicella-zoster vaccination site. The morphology of the lesions included erythematous papules, pseudovesicles, and plaques, with associated pain in two and pruritus in three patients; systemic symptoms ranged from none to low-grade fevers, upper respiratory symptoms, and joint pain. These cases highlight the clinical, diagnostic, and therapeutic implications of herpes zoster in vaccinated children.

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Cortisol evaluation during the acute phase of traumatic brain injury – a prospective study

Abstract

Background

Biochemical diagnosis of adrenal insufficiency (AI) is difficult in the context of traumatic brain injury (TBI)

Aim

to assess the frequency and predictive factors of AI in victims of TBI from Algiers.

Methods

Between November 2009 and December 2013, TBI victims had a single 8-9 a.m. serum cortisol measurement during the acute post injury period (0-7 days). AI was defined according to basal cortisol levels of 83, 276 and 414 nmol/L. Variables studied were TBI severity according to Glasgow coma scale, duration of intubation and coma, pupillary status, hypotension, anemia, brain imaging findings, diabetes insipidus and medication. Insulin tolerance test was performed during the recovery phase, defining AI as peak cortisol <500 nmol/L.

Results

Cortisol samples were obtained at median 3 (1-7) days from 277 patients (257M: 20F) aged 32 (18-65) years. Acute AI frequency was 8 (2.8%), 20 (21%) and 35 (37%) respectively using the three cortisol cut-offs. Factors predicting AI were diastolic hypotension, sedative medication, diabetes insipidus, skull base fracture and intra-parenchymal haematoma. Mortality was highest in patients with acute cortisol <276nmol/L (44.6% with OR for death 1.64, 95% CI 0.92-3.0, p=0.12). During the recovery phase, AI was present in 3/3, 12/24, 4/16 and 20/66 patients with week 1 cortisol <83, 83-276, 277-414 and >414nmol/L.

Conclusion

Hydrocortisone replacement is advised in TBI patients with morning cortisol <276 nmol/L or those <414 nmol/L with additional risk factors for AI. Since acute and subsequent AI are poorly correlated patients with moderate/severe TBI require adrenal re-evaluation during the recovery phase.

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The Free Androgen Index is inaccurate in women when the SHBG concentration is low

Abstract

Objective/Context

The free androgen index (FAI) is known to give erroneous results in men but it is still a commonly used test for the investigation of hyperandrogenism in women. This study aimed to compare the results of the FAI with the gold standard equilibrium dialysis method for free testosterone in women.

Design/Patients

Free serum testosterone T (ED-T) and total serum T (T) were measured by equilibrium dialysis and LC-MS/MS in patients with polycystic ovarian syndrome (n=130), normal female controls (n=53) and normal males (n=120). Calculated free T (cFT) and free androgen index (FAI) were also measured in these patients. In addition cFT was retrospectively calculated in 4223 female patients with a normal T (<1.6 nmol/L) routinely investigated for hyperandrogenism.

Results

The cFT showed good agreement with measured ED-T and the ratio cFT/ED-T was stable across all SHBG concentrations. In contrast the FAI/ED-T ratio and the FAI/cFT ratio increased when the concentration of SHBG fell below 30 nmol/L.

Conclusions

The FAI is not a reliable indicator of free T when the SHBG concentration is low and would give misleading information in a large number of women being investigated for hyperandrogenism.

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Title page / Editorial Board

Publication date: February 2018
Source:Cancer Epidemiology, Volume 52

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Publication date: February 2018
Source:Cancer Epidemiology, Volume 52

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Metastatic melanoma with dedifferentiation and extensive rhabdomyosarcomatous heterologous component

Melanoma may undergo dedifferentiation and sarcomatous transformation with loss of melanocytic markers. Dedifferentiated melanoma rarely forms true rhabdomyoblasts with skeletal muscle immunophenotype (rhabdomyosarcomatous heterologous component). A 52 year-old woman was diagnosed with invasive melanoma (Breslow depth 0.83 mm) of the upper back in 2012, treated by wide local excision only. In 2013, an axillary mass was excised to show metastatic melanoma with two morphologies: an epithelioid morphology expressing S100 and MART-1 and a spindled morphology with loss of melanocytic markers but strong expression of desmin. This metastasis was found to have BRAF V600E mutation. In 2015, a thoracic epidural mass biopsy showed atypical spindle cells with focal HMB-45 but essentially no S100 expression. Numerous rhabdomyoblasts, some with striations that were strongly positive for desmin and myogenin, were present. In 2016, a right nephrectomy was performed for metastasis to the kidney, and showed sheets of spindle cells and rhabdomyoblasts expressing desmin and myogenin but not S100. Only focal areas demonstrated expression of HMB-45 and SOX-10, supporting the melanocytic origin of the tumor. The numerous rhabdomyoblasts and the loss of S100 expression in the metastatic lesions in this case could have easily led to misdiagnosis if the clinical history was not known.

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Surface texture keeps katydids on the hop

Publication date: Available online 5 February 2018
Source:Materials Today
Author(s): Cordelia Sealy

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Tools, techniques, and technologies for pollution prevention, control, and resource recovery

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MiR-93-5p targeting PTEN regulates the NMDA-induced autophagy of retinal ganglion cells via AKT/mTOR pathway in glaucoma

Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Rui Li, Yiping Jin, Qian Li, Xinghuai Sun, Haohao Zhu, Hongping Cui
BackgroundGlaucoma is hallmarked with the death of retinal neurons in the ganglion cell layer, which results in irreversible vision loss. The abnormal levels of miRNA have been associated with glaucoma. Our study purposed to explore the underlying molecule mechanism of miR-93-5p in NMDA-induced glaucoma.MethodsThe Sprague-Dawley (SD) rats were used for the establishment of glaucoma model with the injection of NMDA. Vision behavior test were performed on the glaucoma rats. MiR-93-5p expression was determined by real-time PCR. The levels of autophagy-related protein and PTEN were assessed by Western blot assays. TUNEL assay and flow cytometry were performed to analyze cell apoptosis in vivo and in vitro, respectively. And cell viability was examined by CKK-8 assay. The relationship between miR-93-5p and PTEN was confirmed by Dual-Luciferase reporter gene system.ResultsNMDA-induced glaucoma rats exhibited less time in the dark box, suggesting the recession of their vision. Moreover, the retinal ganglion cell (RGC) viability was reduced not only in the glaucoma rat models but also in the glaucoma RGC models. The autophagy-related protein was obviously increased in the NMDA-treated rats or RGCs. PTEN regulated the autophagy of RGCs through AKT/mTOR pathway in NMDA-treated RGCs. MiR-93-5p could target regulate PTEN negatively, and exhibit the similar effect of 3-MA on the survival of RGCs.ConclusionUp-regulation of miR-93-5p binding with PTEN suppressed the autophagy of RGCs through AKT/mTOR pathway in NMDA-induced glaucoma.

http://ift.tt/2GRC4cH

Effective long-term solution to therapeutic remission in Inflammatory Bowel Disease: Role of Azathioprine

Publication date: April 2018
Source:Biomedicine & Pharmacotherapy, Volume 100
Author(s): Lyla Adam, Alisa Phulukdaree, Prashilla Soma
Azathioprine (AZA) is a well-known immunosuppressant used for many years for its ability to ensure long term disease remission in inflammatory bowel diseases (IBD) at an affordable cost to the public. However, the side effect profile has raised many concerns with numerous investigations into the risk, cause and prevention of these effects. Much of the side effect profile of AZA can be linked to a single nucleotide polymorphism (SNP) in the thiopurine methyltransferase (TPMT) gene which ensures the breakdown and efficacy of AZA. Mutated TPMT alleles result in low or deficient TPMT levels which directly correlate to cytotoxity. This is a review of the role of AZA in the treatment of IBD. Knowing a patient's TPMT status allows the prescribing doctor to make an informed decision about dosage and be more alert to the signs of cytotoxicity. It is essential to include "early warning" SNP testing into common practice to ensure therapeutic efficacy.

http://ift.tt/2s9Mt09

In Vitro and In Vivo Characterization of a Preclinical Radiation-Adapted Model for Ewing Sarcoma

Publication date: Available online 5 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Mary Carroll Shapiro, Tien Tang, Atreyi Dasgupta, Lyazat Kurenbekova, Ryan Shuck, M. Waleed Gaber, Jason T. Yustein
PurposeRadiation therapy (RT) is a viable therapeutic option for Ewing sarcoma (ES) patients. However, little progress has been made to elucidate mechanisms of radioresistance. This study establishes a novel ES radiation-adapted model designed to assess molecular and fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) alterations secondary RT.Methods and MaterialsRadiation-adapted cell lines (RACL) were created in vitro by exposing ES human cell lines to fractionated doses of radiation. Assays to assess migration/invasion potential and RNA expression were performed on the RACL. Orthotopic intra-tibial in vivo investigations were performed with radiation-sensitive and radiation-adapted ES cells to generate tumors. Transplanted mice were imaged using ¹⁸F-FDG-PET followed by fractionated RT directed at the primary tumor. Mice were monitored for tumor regression and change in metabolic activity using ¹⁸F-FDG PET imaging. Protein expression analyses were performed on the RACL and orthotopic tumors.ResultsExposure to fractionated doses of radiation caused a significant increase in migratory and invasive properties in the RACL when compared to non-irradiated wild type ES cells. RACL transcriptomic and proteomic analysis suggests enhanced activation of the mTOR-AKT pathway when compared to wild type ES cells. Radiation-adapted tumors demonstrated significantly less tumor regression (p = 0.03) compared to wild type tumors. Wild type tumors also had decreased expression of lactate dehydrogenase A (LDHA) protein and significantly lower metabolic activity after RT compared to radiation-adapted tumors (p = 0.03).ConclusionsWe developed novel in vitro and in vivo radiation-adapted ES models. In vitro investigations revealed increased migratory and invasive phenotypes in the RACL. In vivo investigations demonstrated increased metabolic activity and significantly decreased sensitivity to RT in the radiation-adapted tumors as demonstrated by growth response curves and ¹⁸F-FDG PET activity. Investigations of the RACL identified possible radiosensitizing-dependent targets in LDHA and mTOR-AKT pathway.

Teaser

Ewing sarcoma (ES) is the second most common pediatric bone cancer, and patients with relapsed/resistant disease have a five-year overall survival rate of only 15-20%. Front-line standard of care treatment for patients with ES includes chemotherapy and local control with surgery and/or radiation. We have developed novel in vitro and in vivo radiation-adapted ES models that demonstrate a relationship between metabolism and radioresistance as well as identify several candidate biomarkers for radioresistant disease in ES.

http://ift.tt/2BKwWb8

Does Prophylactic Radiotherapy to avoid Gynecomastia in Patients with Prostate Cancer increase the risk of Breast Cancer?

Publication date: Available online 5 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Bjørg Y. Aksnessæther, Arne Solberg, Olbjørn H. Klepp, Tor Åge Myklebust, Eva Skovlund, Solveig Roth Hoff, Lars J. Vatten, Jo-Åsmund Lund
PurposeProstate cancer (PC) patients treated with antiandrogen monotherapy are offered prophylactic radiotherapy to the breast buds (PRT) to avoid gynecomastia. The aim of this study was to evaluate whether the risk of breast cancer (BC) in men with PC as their first cancer diagnosis, was influenced by PRT.Methods and MaterialsFrom the Norwegian Cancer Registry we collected data on all patients with PC as their first cancer diagnosis diagnosed between 1997- 2014. We registered all radiotherapy given to the patients in the same period, and the occurrence of BC diagnosed 3 months or more following the PC diagnosis. The histopathological diagnoses of all BC cases were collected. Subdistribution hazard ratios (SHR) for the risk of BC in PRT and non-PRT treated patients were estimated. A standardized incidence ratio (SIR) for BC was calculated by comparing our cohort to the standard male population.ResultsWe analyzed 59 169 patients with PC, whom 7864 (13.3%) had received PRT. Median follow-up time was 4 years. Three of 12 men diagnosed with BC had received PRT, and two of three were phyllodes tumors. The risk of BC was not statistically significantly different in patients given RT as compared to the non-RT patients, SHR 1.62 95% CI 0.41-5.62, adjusted for age and time of diagnosis. SIR was 0.996 95 % CI 0.57-1.75.ConclusionsIn this registry based study, we did not find an increased risk of BC in PC patients treated with PRT. The number of BC cases in our study was low, and the risk of secondary breast cancer following PRT seems to be negligible. The incidence of BC may, however rise with additional follow-up. It is noteworthy that two patients who had been treated with PRT were diagnosed with malignant phyllodes tumor, an extremely rare type of BC associated with gynecomastia.

Teaser

Nordic patients with prostate cancer receive prophylactic radiotherapy to the breast buds to avoid gynecomastia when treated with antiandrogen monotherapy. In this study with data from the Norwegian Cancer Registry, we did not find increased risk of breast cancer (BC) in irradiated patients compared to non-irradiated patients. It is noteworthy that in the RT group, there were two cases of malignant phyllodes breast tumor, an extremely rare type of BC associated with gynecomastia.

http://ift.tt/2BcjeN5

A daily single dose of a novel modafinil analogue CE-123 improves memory acquisition and memory retrieval

Publication date: 2 May 2018
Source:Behavioural Brain Research, Volume 343
Author(s): Martina Kristofova, Yogesh D. Aher, Marija Ilic, Bojana Radoman, Predrag Kalaba, Vladimir Dragacevic, Nilima Y. Aher, Johann Leban, Volker Korz, Lisa Zanon, Winfried Neuhaus, Marcus Wieder, Thierry Langer, Ernst Urban, Harald H. Sitte, Harald Hoeger, Gert Lubec, Jana Aradska
Dopamine reuptake inhibitors have been shown to improve cognitive parameters in various tasks and animal models. We recently reported a series of modafinil analogues, of which the most promising, 5-((benzhydrylsulfinyl)methyl) thiazole (CE-123), was selected for further development. The present study aims to characterize pharmacological properties of CE-123 and to investigate the potential to enhance memory performance in a rat model. In vitro transporter assays were performed in cells expressing human transporters. CE-123 blocked uptake of [3H] dopamine (IC50 = 4.606 μM) while effects on serotonin (SERT) and the norepinephrine transporter (NET) were negligible. Blood-brain barrier and pharmacokinetic studies showed that the compound reached the brain and lower elimination than R-modafinil. The Pro-cognitive effect was evaluated in a spatial hole-board task in male Sprague-Dawley rats and CE-123 enhances memory acquisition and memory retrieval, represented by significantly increased reference memory indices and shortened latency. Since DAT blockers can be considered as indirect dopamine receptor agonists, western blotting was used to quantify protein levels of dopamine receptors D1R, D2R and D5R and DAT in the synaptosomal fraction of hippocampal subregions CA1, CA3 and dentate gyrus (DG). CE-123 administration in rats increased total DAT levels and D1R protein levels were significantly increased in CA1 and CA3 in treated/trained groups. The increase of D5R was observed in DG only. Dopamine receptors, particularly D1R, seem to play a role in mediating CE-123-induced memory enhancement. Dopamine reuptake inhibition by CE-123 may represent a novel and improved stimulant therapeutic for impairments of cognitive functions.

http://ift.tt/2EmWEn6

Das Recht am eigenen Bild

Laryngo-Rhino-Otol 2018; 97: 121-122
DOI: 10.1055/s-0043-118941

Article in Thieme eJournals:
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Rhinoplastik

Laryngo-Rhino-Otol 2018; 97: 141-145
DOI: 10.1055/s-0043-124386

Article in Thieme eJournals:
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Endoskopisch ausgeführte Tympanoplastik mit Vorteilen

Laryngo-Rhino-Otol 2018; 97: 82-83
DOI: 10.1055/s-0043-121839

Kuo CH et al. Comparison of endoscopic and microscopic tympanoplasty. Eur Arch Otorhinolaryngol 2017;274:2727–2732 Welche Vor-und Nachteile hat die endoskopisch durchgeführte Tympanoplastik? Wie sieht die Erfolgs- und die Komplikationsrate bei alleiniger Rekonstruktion des Trommelfells und bei Wiederherstellung einer funktionalen Gehörknöchelchenkette aus?
[...]

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Fragen für die Facharztprüfung

Laryngo-Rhino-Otol 2018; 97: 138-139
DOI: 10.1055/s-0044-101037

Article in Thieme eJournals:
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Medikamentöse Therapie des Schilddrüsenknotens

Laryngo-Rhino-Otol 2018; 97: 89-91
DOI: 10.1055/s-0043-124607

Während in Regionen mit ausreichender Iodversorgung die Therapie des Schilddrüsenknotens mit Levothyroxin weitgehend verlassen wurde und auch nicht mehr in den Leitlinien empfohlen wird, gibt es für eine medikamentöse Therapie von Schilddrüsenknoten in Deutschland eine Indikation, wie die randomisierte, placebokontrollierte LISA-Studie nachgewiesen hat.Wesentlicher Grund ist ein leichter Iodmangel bei Patienten mit Schilddrüsenknoten. In der LISA-Studie führte eine Levothyroxin-Iodid-Kombinationstherapie zu einer mindestens 50 %igen Volumenreduktion der Knoten bei 21,6 % der Patienten gegenüber bei nur 5,2 % der Placebo-Behandelten.Unter der kombinierten L-T4-Iodidtherapie wird der TSH-Wert im unteren Referenzbereich eingestellt, eine TSH-Suppression (latente Hyperthyreose) muss vermieden werden, da sie zu Herzrhythmusstörungen führen kann.Im höheren Alter muss aufgrund der kardiovaskulären Risiken die Indikation zu einer Schilddrüsenhormontherapie überprüft, die Dosis häufig reduziert oder die Therapie abgesetzt werden.
[...]

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Tympanoplastik Typ I im frühen Kindesalter erfolgsversprechend

Laryngo-Rhino-Otol 2018; 97: 84-85
DOI: 10.1055/s-0043-123911

Singh GB et al. Paediatric tympanoplasty: comparative study between patients aged 5–8 years and those aged over 14 years. J Laryngol Otol 2016; 130: 635–639
[...]

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Aktueller Status der Therapie und Prophylaxe des Oropharynxkarzinoms

Laryngo-Rhino-Otol 2018; 97: 123-137
DOI: 10.1055/s-0043-121329

Die Inzidenz von Oropharynxkarzinomen nimmt weltweit signifikant zu. Aufgrund ihres Zusammenhangs mit chronischem Tabak-/Alkoholkonsum, zunehmend aber auch mit dem humanen Papillomavirus HPV-16, sind die Oropharynxkarzinome eine genetisch heterogene Tumorgruppe mit hoher prognostischer Diversifikation. Dieser Beitrag versucht auf Basis der aktuellen Evidenzlage Empfehlungen zu Therapie, Prophylaxe und Früherkennung darzulegen.
[...]

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Durchführung und Interpretation der FEES (Fiberoptic Endoscopic Evaluation of Swallowing)

Laryngo-Rhino-Otol 2018; 97: 86-88
DOI: 10.1055/s-0043-125007

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„Das Thema künstliche Intelligenz ist in der Radiologie angekommen“

Laryngo-Rhino-Otol 2018; 97: 140-140
DOI: 10.1055/s-0043-125319

Zum zweiten Mal nach 2017 findet im Februar 2018 der Kongress Emerging Technologies in Medicine – ETIM statt. Initiator des Zukunftskongresses ist Prof. Dr. Michael Forsting, Direktor der Universitätsradiologie Essen. Im Interview skizziert er die Themen der kommenden Tagung und welche Bedeutung sie für die Radiologie haben.
[...]

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Seltener Nasennebenhöhlen Tumor

Laryngo-Rhino-Otol
DOI: 10.1055/s-0043-123652

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Kommentar der Schriftleitung

Laryngo-Rhino-Otol 2018; 97: 79-80
DOI: 10.1055/s-0044-100459

[...]

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Tropical Dermatology, 2nd ed

http://ift.tt/2nIa2rs

The effect of dietary selenium addition on the concentrations of heavy metals in the tissues of fallow deer ( Dama dama L.) in Croatia

Abstract

The aim of this research was to determine the concentrations of cadmium, lead, mercury, and arsenic and the essential elements iron and selenium in the tissues (muscle, kidney, liver, spleen, and fat) of fallow deer (Dama dama L.) without and with supplemental selenium addition. Another aim was to determine the effect of selenium addition on the indicators of oxidative stress, namely, the levels of superoxide dismutase, glutathione peroxidase, glutathione, and vitamin E. The research was carried out with 40 fallow deer during two research periods. Supplemental feed without selenium addition was provided during the first research period, and supplemental feed with added selenium (3 mg/kg) was provided for 60 days during the second research period. The concentration of selenium in tissues was higher in the second research period than in the first research period (in kidney tissue, 0.957 vs. 0.688 mg/kg, P < 0.05). The dietary addition of selenium decreased (P < 0.05) the concentrations of some heavy metals (lead in the spleen = 0.06 vs. 0.27 mg/kg and in the fatty tissue = 0.17 vs. 0.69 mg/kg; arsenic in the muscle tissue = 0.005 vs. 0.014 mg/kg, liver = 0.003 vs. 0.009 mg/kg, spleen = 0.004 vs. 0.013 mg/kg, and fat = 0.008 vs. 0.016 mg/kg). The activity of glutathione peroxidase was significantly higher (P < 0.05) in the second research period than in the first research period (1375.36 vs. 933.23 U/L).

http://ift.tt/2FRfVtX

In situ investigation of heavy metals at trace concentrations in greenhouse soils via portable X-ray fluorescence spectroscopy

Abstract

Soil pollution by heavy metals (HMs) has rapidly become a major threat to vegetable security. Nearly all cultivated soils are at risk of metal accumulation, and greenhouse soils are among the most heavily impacted soils. In this study, a rapid assessment of HMs at trace concentrations was conducted via portable X-ray fluorescence (PXRF) spectroscopy in Shouguang, China. Measurements were made via PXRF under in situ, ex situ and sieved conditions and by inductively coupled plasma mass spectrometry (ICP-MS) after acid digestion. The performance of each PXRF measure relative to the ICP-MS method was assessed by linear regression. Redundancy analysis was performed to quantify the proportion of explained variability between the PXRF and ICP-MS data. Evaluation of the possible sources of HMs and their potential risks was then conducted by multivariate analysis. The results showed that the PXRF data were closely correlated with ICP-MS quantification for Cu, Mn and Zn, whereas no significant correlations were found for As, Ni and Pb. The uncertainties of PXRF measurement derived from soil heterogeneity accounted for 20.02% of total variability and those from moisture and particle size accounted for 20.15%. The geo-accumulation index (I_geo) indicated that the greenhouse soils were potentially contaminated by Cu and Zn (I_geo > 0), which can be attributed to anthropogenic activities. Overall, PXRF spectroscopy is promising as a rapid and nondestructive in situ technique for assessing the potential risks of HMs at trace concentrations in greenhouse soils.

http://ift.tt/2E4bvDF

Response to: baseline asthma burden, comorbidities, and biomarkers in omalizumab-treated patients in PROSPERO

We read with interest comments from Oppenheimer and Greenberger1 highlighting the baseline findings of the PROSPERO trial that describe a real-world population with moderate to severe asthma accompanied by multiple comorbidities, a substantial disease burden, and a heterogeneous biomarker profile who were initiated on omalizumab.2 We agree with their conclusions that patients with severe asthma represent a challenging population and that multiple factors must be considered when evaluating patients as candidates for biologic therapies.

http://ift.tt/2BWp9mj

Biologics in allergic and immunologic diseases: promises and challenges in the era of personalized medicine

Discovery of new biologics offer promise in the treatment of chronic, refractory allergic and immunologic conditions. Emerging biologic therapies have ushered in an era of personalized medicine, also referred to as precision medicine, whereby physicians can choose targeted therapies based on disease phenotype. Undoubtedly, this has been a significant advance for patients with conditions such as severe asthma, and also offers hope for successful management of other allergic and immunologic conditions, such as severe atopic dermatitis and refractory chronic urticaria.

http://ift.tt/2nEspOC

Slow-Wave Sleep: From the Cell to the Clinic

In recent decades, increasing evidence has positioned slow-wave sleep (SWS) as a major actor in neurophysiological phenomena such as glucose metabolism, hormone release, immunity and memory. This proposed role for SWS, coupled with observations of impaired SWS in several pathologies as well as in aging, has led some researchers to implement methods that could specifically enhance SWS.This review aims to gather the current knowledge extending from the cell to the clinic, in order to construct an overview of what is currently known about so-called SWS.

http://ift.tt/2BcT9xB

Mesenchymal stem cell (MSC)-mediated survival of insulin producing pancreatic β-cells during cellular stress involves signalling via Akt and ERK1/2

Publication date: Available online 5 February 2018
Source:Molecular and Cellular Endocrinology
Author(s): Chune Liu, Weiwei Zhang, Natia Peradze, Leonie Lang, Jan Straetener, Peter J. Feilen, Marcus Alt, Christina Jäger, Katharina Laubner, Nikolaos Perakakis, Jochen Seufert, Günter Päth
Mesenchymal stem cells (MSC) are of interest for cell therapy since their secreted factors mediate immunomodulation and support tissue regeneration. This study investigated the direct humoral interactions between MSC and pancreatic β-cells using human telomerase-immortalized MSC (hMSC-TERT) and rat insulinoma-derived INS-1E β-cells. hMSC-TERT supported survival of cocultured INS-1E β-cells during cellular stress by alloxan (ALX) and streptozotocin (STZ), but not in response to IL-1β. Accordingly, hMSC-TERT had no effect on inflammatory cytokine-related signalling via NF-kB and p-JNK but maintained p-Akt and upregulated p-ERK1/2. Inhibition of either p-Akt or p-ERK1/2 did not abolish protection by hMSC-TERT but activated the respective non-inhibited pathway. This suggests that one pathway compensates for the other. Main results were confirmed in mouse islets except hMSC-TERT-mediated upregulation of p-ERK1/2. Therefore, MSC promote β-cell survival by preservation of p-Akt signalling and further involve p-ERK1/2 activation in certain conditions such as loss of p-Akt or insulinoma background.

http://ift.tt/2nEUipW

Increasing Pulmonary Arterial Pressure at Low Level of Exercise in Asymptomatic, Organic Mitral Regurgitation

http://ift.tt/2EkYNQ0

JACC Instructions for Authors

http://ift.tt/2EjaPJI

Compliance With Guideline-Directed Medical Therapy in Contemporary Coronary Revascularization Trials

AbstractBackground

Despite the well-established benefits of secondary cardiovascular prevention, the importance of concurrent medical therapy in clinical trials of coronary revascularization is often overlooked.

Objectives

The goal of this study was to assess compliance with guideline-directed medical therapy (GDMT) in clinical trials and its potential impact on the comparison between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG).

Methods

The Cochrane Central Register of Controlled Trials and MEDLINE were searched from 2005 to August 2017. Clinical trial registries and reference lists of relevant studies were also searched. Randomized controlled trials comparing PCI with drug-eluting stents versus CABG and reporting medical therapy after revascularization were included. The study outcome was compliance with GDMT, defined as the following: 1) any antiplatelet agent plus beta-blocker plus statin (GDMT1); and 2) any antiplatelet agent plus beta-blocker plus statin plus angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (GDMT2). Data collection and analysis were performed according to the methodological recommendations of The Cochrane Collaboration.

Results

From a total of 439 references, 5 trials were included based on our inclusion and exclusion criteria. Overall, compliance with GDMT1 was low and decreased over time from 67% at 1 year to 53% at 5 years. Compliance with GDMT2 was even lower and decreased from 40% at 1 year to 38% at 5 years. Compliance with both GDMT1 and GDMT2 was higher in PCI than in CABG at all time points. Meta-regression suggested an association between lower use of GDMT1 and adverse clinical outcomes in PCI versus CABG at 5 years.

Conclusions

Compliance with GDMT in contemporary clinical trials remains suboptimal and is significantly lower after CABG than after PCI, which may influence the comparison of clinical trial endpoints between those study groups.

http://ift.tt/2FPBaw8

Reply: LDL-Cholesterol and Atherosclerotic Cardiovascular Disease: Innocent Bystander or Essential Ingredient?

http://ift.tt/2Ena5U0

Suboptimal Medical Therapy After Coronary Revascularization: A Missed Opportunity

http://ift.tt/2Ejdvai

Left Ventricle Replacement Fibrosis Detected by CMR Associated With Cardiovascular Events in Systemic Sclerosis Patients

http://ift.tt/2EjaIOi

Evaluating Chest Pain in the Emergency Department: Searching for the Optimal Gatekeeper

http://ift.tt/2EjdjI6

Is Skipping Breakfast a Marker for Current Smoking?

http://ift.tt/2Ejamaq

Lipids, Lipoproteins, and Metabolites and Risk of Myocardial Infarction and Stroke

AbstractBackground

Blood lipids are established risk factors for myocardial infarction (MI), but uncertainty persists about the relevance of lipids, lipoprotein particles, and circulating metabolites for MI and stroke subtypes.

Objectives

This study sought to investigate the associations of plasma metabolic markers with risks of incident MI, ischemic stroke (IS), and intracerebral hemorrhage (ICH).

Methods

In a nested case-control study (912 MI, 1,146 IS, and 1,138 ICH cases, and 1,466 common control subjects) 30 to 79 years of age in China Kadoorie Biobank, nuclear magnetic resonance spectroscopy measured 225 metabolic markers in baseline plasma samples. Logistic regression was used to estimate adjusted odds ratios (ORs) for a 1-SD higher metabolic marker.

Results

Very low-, intermediate-, and low-density lipoprotein particles were positively associated with MI and IS. High-density lipoprotein (HDL) particles were inversely associated with MI apart from small HDL. In contrast, no lipoprotein particles were associated with ICH. Cholesterol in large HDL was inversely associated with MI and IS (OR: 0.79 and 0.88, respectively), whereas cholesterol in small HDL was not (OR: 0.99 and 1.06, respectively). Triglycerides within all lipoproteins, including most HDL particles, were positively associated with MI, with a similar pattern for IS. Glycoprotein acetyls, ketone bodies, glucose, and docosahexaenoic acid were associated with all 3 diseases. The 225 metabolic markers showed concordant associations between MI and IS, but not with ICH.

Conclusions

Lipoproteins and lipids showed similar associations with MI and IS, but not with ICH. Within HDL particles, cholesterol concentrations were inversely associated, whereas triglyceride concentrations were positively associated with MI. Glycoprotein acetyls and several non–lipid-related metabolites associated with all 3 diseases.

http://ift.tt/2FRauLE

Metabolic Surgery: Weight Loss, Diabetes, and Beyond

Abstract

The alarming rise in the worldwide prevalence of obesity is paralleled by an increasing burden of type 2 diabetes mellitus. Metabolic surgery is the most effective means of obtaining substantial and durable weight loss in individuals with obesity. Randomized trials have recently shown the superiority of surgery over medical treatment alone in achieving improved glycemic control, as well as a reduction in cardiovascular risk factors. The mechanisms seem to extend beyond the magnitude of weight loss alone and include improvements in incretin profiles, insulin secretion, and insulin sensitivity. Moreover, observational data suggest that the reduction in cardiovascular risk factors translates to better patient outcomes. This review describes commonly used metabolic surgical procedures and their current indications and summarizes the evidence related to weight loss and glycemic outcomes. It further examines their potential effects on cardiovascular outcomes and mortality and discusses future perspectives.

http://ift.tt/2FOEK9F

Cardiovascular Risk Beyond Low-Density Lipoprotein Cholesterol

http://ift.tt/2EjdeEi

Tele-Cardiology in the Syrian War

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Long-Term Sirolimus for Primary Immunosuppression in Heart Transplant Recipients

AbstractBackground

Small studies have reported superiority of sirolimus (SRL) over calcineurin inhibitor (CNI) in mitigating cardiac allograft vasculopathy (CAV) after heart transplantation (HT). However, data on the long-term effect on CAV progression and clinical outcomes are lacking.

Objectives

The aim of this study was to test the long-term safety and efficacy of conversion from CNI to SRL as maintenance therapy on CAV progression and outcomes after HT.

Methods

A cohort of 402 patients who underwent HT and were either treated with CNI alone (n = 134) or converted from CNI to SRL (n = 268) as primary immunosuppression was analyzed. CAV progression was assessed using serial coronary intravascular ultrasound during treatment with CNI (n = 99) and after conversion to SRL (n = 235) in patients who underwent at least 2 intravascular ultrasound studies.

Results

The progression in plaque volume (2.8 ± 2.3 mm³/mm vs. 0.46 ± 1.8 mm³/mm; p < 0.0001) and plaque index (plaque volume–to–vessel volume ratio) (12.2 ± 9.6% vs. 1.1 ± 7.9%; p < 0.0001) were significantly attenuated when treated with SRL compared with CNI. Over a mean follow-up period of 8.9 years from time of HT, all-cause mortality occurred in 25.6% of the patients and was lower during treatment with SRL compared with CNI (adjusted hazard ratio: 0.47; 95% confidence interval: 0.31 to 0.70; p = 0.0002), and CAV-related events were also less frequent during treatment with SRL (adjusted hazard ratio: 0.35; 95% confidence interval: 0.21 to 0.59; p < 0.0001). Further analyses suggested more attenuation of CAV and more favorable clinical outcomes with earlier conversion to SRL (≤2 years) compared with late conversion (>2 years) after HT.

Conclusions

Early conversion to SRL is associated with attenuated CAV progression and with lower long-term mortality and fewer CAV-related events compared with continued CNI use.

http://ift.tt/2FMwK96

Impact of Sleep Duration and Race on Recurrent Cardiovascular Events Following Acute Coronary Syndrome

http://ift.tt/2FNRM7o

The Return of the mTOR Inhibitors: Getting it Right in Patients After Cardiac Transplantation

http://ift.tt/2Ekqj01

LDL-Cholesterol and Atherosclerotic Cardiovascular Disease: Innocent Bystander or Essential Ingredient

http://ift.tt/2FOrJ02

Activation of Serine One-Carbon Metabolism by Calcineurin A{beta}1 Reduces Myocardial Hypertrophy and Improves Ventricular Function

AbstractBackground

In response to pressure overload, the heart develops ventricular hypertrophy that progressively decompensates and leads to heart failure. This pathological hypertrophy is mediated, among others, by the phosphatase calcineurin and is characterized by metabolic changes that impair energy production by mitochondria.

Objectives

The authors aimed to determine the role of the calcineurin splicing variant CnAβ1 in the context of cardiac hypertrophy and its mechanism of action.

Methods

Transgenic mice overexpressing CnAβ1 specifically in cardiomyocytes and mice lacking the unique C-terminal domain in CnAβ1 (CnAβ1ⁱ¹² mice) were used. Pressure overload hypertrophy was induced by transaortic constriction. Cardiac function was measured by echocardiography. Mice were characterized using various molecular analyses.

Results

In contrast to other calcineurin isoforms, the authors show here that cardiac-specific overexpression of CnAβ1 in transgenic mice reduces cardiac hypertrophy and improves cardiac function. This effect is mediated by activation of serine and one-carbon metabolism, and the production of antioxidant mediators that prevent mitochondrial protein oxidation and preserve ATP production. The induction of enzymes involved in this metabolic pathway by CnAβ1 is dependent on mTOR activity. Inhibition of serine and one-carbon metabolism blocks the beneficial effects of CnAβ1. CnAβ1ⁱ¹² mice show increased cardiac hypertrophy and declined contractility.

Conclusions

The metabolic reprogramming induced by CnAβ1 redefines the role of calcineurin in the heart and shows for the first time that activation of the serine and one-carbon pathway has beneficial effects on cardiac hypertrophy and function, paving the way for new therapeutic approaches.

http://ift.tt/2FPATth

Mobility of 232Th and 210Po in red mud

Publication date: April 2018
Source:Journal of Environmental Radioactivity, Volumes 184–185
Author(s): Miklós Hegedűs, Edit Tóth-Bodrogi, Jácint Jónás, János Somlai, Tibor Kovács
The valorization of industrial by-products such as red mud became a tempting opportunity, but the understanding of the risks involved is required for the safe utilization of these products. One of the risks involved are the elevated levels of radionuclides (in the 100–1300 Bq/kg range for both the ²³⁸U and ²³² Th decay chains, but usually lower than 1000 Bq/kg, which is the recommended limit for excemption or clearance according to the EU BSS released in 2013) in red mud that can affect human health. There is no satisfactory answer for the utilization of red mud; the main current solution is still almost exclusively disposal into a landfill. For the safe utilization and deposition of red mud, it is important to be able to assess the leaching behaviour of radionuclides. Because there is no commonly accepted measurement protocol for testing the leaching of radionuclides in the EU a combined measurement protocol was made and tested based on heavy metal leaching methods. The leaching features of red mud were studied by methods compliant with the MSZ-21470-50 Hungarian standard, the CEN/TS 14429 standard and the Tessier sequential extraction method for ²³²Th and ²¹⁰Po. The leached solutions were taken to radiochemical separation followed by spontaneous deposition for Po and electrodeposition for Th. The 332 ± 33 Bq/kg ²³²Th content was minimally mobile, 1% became available for distilled water 1% and 6% for Lakanen-Erviö solution; the Tessier extraction showed minimal mobility in the first four steps, while more than 85% remained in the residue. The ²¹⁰Po measurements had a severe disturbing effect in many cases, probably due to large amounts of iron present in the red mud, from the 310 ± 12 Bq/kg by aqua regia digestion, distilled water mobilized 23%, while Lakanen-Erviö solution mobilized ∼13%. The proposed protocol is suitable for the analysis of Th and Po leaching behaviour.

http://ift.tt/2sdMPTD

Hybrid porous thin films: Opportunities and challenges for sensing applications

Publication date: 1 May 2018
Source:Biosensors and Bioelectronics, Volume 104
Author(s): Pawan Kumar, Ki-Hyun Kim, Kowsalya Vellingiri, Pallabi Samaddar, Parveen Kumar, Akash Deep, Naresh Kumar
In this paper, the scientific progress in the field of thin film materials and their associated sensing technologies are described comprehensively to address the directions for future research and developments as per the need of modern-day technologies. To begin with, we briefly discussed the fundamental synthesis approaches for advanced thin films with an emphasis on the properties necessary for controlled fabrication (e.g., the elemental ratio and spatial arrangement). Subsequently, we explored the control, characterization, and optimization of hybrid porous thin films with respect to diverse sensing applications. The application of hybrid porous thin film materials has also been discussed in relation to the mechanisms used for biological, optical, electrical, acoustic, and other advanced sensing techniques (e.g., surface-enhanced Raman scattering (SERS)). Finally, conclusions are drawn to highlight the current status of thin film-based sensing technology along with its opportunities and challenges.

http://ift.tt/2sb2aEq

Editorial Board

Publication date: 15 May 2018
Source:Biosensors and Bioelectronics, Volume 105

http://ift.tt/2GOPFS2

Editorial Board

Publication date: 1 May 2018
Source:Biosensors and Bioelectronics, Volume 104

http://ift.tt/2s9il53

Peptide nanoparticles (PNPs) modified disposable platform for sensitive electrochemical cytosensing of DLD-1 cancer cells

Publication date: 1 May 2018
Source:Biosensors and Bioelectronics, Volume 104
Author(s): Yesim Tugce Yaman, Öznur Akbal, Gulcin Bolat, Betul Bozdogan, Emir Baki Denkbas, Serdar Abaci
A novel diphenylalaninamid (FFA) based peptide nanoparticles (PNPs) modified pencil graphite electrodes (PGEs) for construction of electrochemical cytosensor was demonstrated for the first time in this study. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images revealed the spherical nanostructure of the synthesized FFA based PNPs while attenuated total reflectance-fourier transform infrared (ATR-FTIR) spectra provided information about the structure and conformation of proteins in their structure. Self-assembly of PNPs on PGE surface and adhesion of DLD-1 cancer cells on this surface was also characterized by electrochemical measurements. PNP/PGEs acted as a sensitive platform for simple and rapid quantification of low concentration of DLD-1 cancer cells in early diagnosis using the electrochemical impedance method (EIS). The offered cytosensor demonstrated outstanding performance for the detection of DLD-1 cells by the EIS method. The impedance of electronic transduction was associated with the amount of the immobilized cells ranging from 2 × 10² to 2.0 × 10⁵ cellsmL⁻¹ with a limit of detection of 100 cellsmL⁻¹. The efficient performance of the cytosensor was attributed to the well-defined nanostructure and biocompability of PNPs on the substrate.

http://ift.tt/2GOPEgW

Editorial Board

Publication date: February 2018
Source:Journal of Autoimmunity, Volume 87

http://ift.tt/2Ej8EWt

Geochemistry of rare earth elements within waste rocks from the Montviel carbonatite deposit, Québec, Canada

Abstract

Several rare earth element (REE) mine projects around the world are currently at the feasibility stage. Unfortunately, few studies have evaluated the contamination potential of REE and their effects on the environment. In this project, the waste rocks from the carbonatites within the Montviel proterozoic alkaline intrusion (near Lebel-sur-Quévillon, Quebec, Canada) are assessed in this research. The mineralization is mainly constituted by light REE (LREE) fluorocarbonates (qaqarssukite-Ce, kukharenkoite-Ce), LREE carbonates (burbankite, Sr-Ba-Ca-REE, barytocalcite, strontianite, Ba-REE-carbonates), and phosphates (apatite, monazite). The gangue minerals are biotites, chlorite, albite, ankerite, siderite, and calcite. The SEM-EDS analyses show that (i) the majority of REE are associated with the fine fraction (< 106 μm), (ii) REE are mainly associated with carbonates, (iii) all analyzed minerals preferably contain LREE (La, Ce, Pr, Nd, Sm, Eu), (iv) the sum of LREE in each analyzed mineral varies between ~ 3 and 10 wt%, (v) the heavy REE (HREE) identified are Gd and Yb at < 0.4 wt%, and (vi) three groups of carbonate minerals were observed containing variable concentrations of Ca, Na, and F. Furthermore, the mineralogical composition of REE-bearing minerals, REE mobility, and REE speciation was investigated. The leachability and geochemical behavior of these REE-bearing mine wastes were tested using normalized kinetic testing (humidity cells). Leachate results displayed higher LREE concentrations, with decreasing shale-normalized patterns. Thermodynamical equilibrium calculations suggest that the precipitation of secondary REE minerals may control the REE mobility.

http://ift.tt/2E0gRvl

MicroRNA-186 serves as a tumor suppressor in oral squamous cell carcinoma by negatively regulating the protein tyrosine phosphatase SHP2 expression

Publication date: May 2018
Source:Archives of Oral Biology, Volume 89
Author(s): Zhen Cai, Xiu-Yan Hao, Feng-Xin Liu
ObjectiveMicroRNAs (miRs) have been shown to play critical roles in the pathogenesis of oral squamous cell carcinoma (OSCC), the current study is designed to identify the potential role of miR-186 in OSCC.Materials and methodsRealtime polymerase chain reaction was used to determine miR-186 expression in paired tissue samples (OSCC and adjacent normal tissues) and multiple oral cell lines (normal oral keratinocyte HOK cell and OSCC cell lines). Cell viability, colony formation and flow cytometry assays were used to assess the biological function of miR-186. Furthermore, luciferase and western blot assays were used to verify the predicted target of miR-186.ResultsWe found that miR-186 expression was significantly downregulated in OSCC tissues and cell lines. Overexpression of miR-186 produced an anti-growth effect and induced apoptosis in Tca8113 and SCC-25 cells. Luciferase assay revealed that miR-186 directly targeted PTPN11 (a gene encodes the protein tyrosine phosphatase SHP2) mRNA 3′ untranslated region and suppressed its expression. Consistently, MiR-186 and SHP2 were negatively correlated in OSCC tissues. Consequently, miR-186 inhibited signaling activities of Extracellular Regulated protein Kinases (ERK) and Protein kinase B (AKT), which act downstream of SHP2 and are critical for growth of cancer cells.ConclusionWe identify that miR-186 serves as a tumor suppressor in OSCC. Downregulation of this microRNA may lead to a higher expression of oncogenic factor SHP2, which leads to activation of growth promoting signaling. Thus, miR-186 may be a novel and effective therapeutic agent for the treatment of OSCC.

http://ift.tt/2nJ2i9F

Comparative proteomic profiling of human dental pulp stem cells and periodontal ligament stem cells under in vitro osteogenic induction

Publication date: May 2018
Source:Archives of Oral Biology, Volume 89
Author(s): He Wang, Dandan Ma, Xiaoyi Zhang, Shuaimei Xu, Tingting Ning, Buling Wu
ObjectiveThis study aimed to compare the proteomic profiling of human dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) under in vitro osteogenic induction, which imitates the microenvironment during osteo-/odontogenesis of DPSCs and PDLSCs.DesignThe proteomic profiles of osteoinduced DPSCs and PDLSCs from a single donor were compared using the isobaric tag for relative and absolute quantitation (iTRAQ) technique and subsequent bioinformatics analysis.ResultsA total of 159 differentially expressed proteins in PDLSCs and DPSCs were identified, 82 of which had a higher expression level in PDLSCs, while 77 were more highly expressed in DPSCs. Among these enriched proteins, certain members from the collagen, heat shock protein and protein S100 families may distinguish osteoinduced PDLSCs and DPSCs. Gene ontology (GO) classification revealed that a large number of the enriched terms distinguishing PDLSCs and DPSCs are involved in catalytic activity, protein binding, regulation of protein metabolic processes and response to stimulus. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated several involved pathways, including the fatty acid biosynthesis pathway, pantothenate and CoA biosynthesis pathway, arachidonic acid metabolism pathway and PPAR signaling pathway. Further verification showed that the mineralization and migration capacities of PDLSCs were greater than those of DPSCs, in which heat shock protein beta-1, Protein S100-A10 and S100-A11 may play a part.ConclusionsLess than 5% of the differentially expressed proteins make up the comparative proteomic profile between osteoinduced PDLSCs and DPSCs. This study helps to characterize the differences between osteoinduced PDLSCs and DPSCs in vitro.

http://ift.tt/2nEprK5

Maresin 1 regulates autophagy and inflammation in human periodontal ligament cells through glycogen synthase kinase–3β/β-catenin pathway under inflammatory conditions

Publication date: March 2018
Source:Archives of Oral Biology, Volume 87
Author(s): Li Du, Yucheng Li, Weifeng Liu
ObjectiveAccumulating lines of evidence suggest that maresin 1 (MaR-1) exerts anti-inflammatory effects in many cell types and plays beneficial roles in inflammatory disease, such as peritonitis and colitis. Moreover, it has been demonstrated that MaR-1 play protective roles against localized aggressive periodontitis. However, the function and mechanism of MaR-1 in human periodontal ligament cells (PDL) cells from periodontitis are poorly understood. The present study aimed to clarify the effects and molecular mechanism of MaR-1 in PDL cell survival and inflammation.MethodsPDL cells were isolated from the middle third of the root surface of premolars from four healthy humans; MTT assay and cell death detection ELISA assay were used to detect cell survival and apoptosis; Inflammatory cytokines level was measured by ELISA assay; RT-PCR and western blot was used to measure the mRNA and protein expression in this study.ResultsHere we found that MaR-1 treatment markedly promotes survival and inhibits apoptosis in PDL cell treated by LPS. MaR-1 treatment strikingly suppressed the production of LPS-induced pro-inflammatory cytokines IL-6, IL-8, TNF-α and IL-1β. MaR-1 also promotes autophagy by increasing the ratio of LC3II/LC3I, the level of beclin-1 and reduced the expression of p62 in LPS treated PDL cells, which is beneficial to cell survival. Moreover, the results showed that MaR-1-mediated autophagy is dependent on the glycogen synthase kinase–3β(GSK-3β)/β-catenin signal pathway. The inhibitor of autophagy 3-MA and the inhibitor of the GSK-3β/β-catenin signal pathway LiCL both reverse the effects of MaR-1 on LPS-treated PDL cell survival and inflammation.ConclusionMaR-1 promotes cell survival and alleviates cell inflammation by activating GSK-3β/β-catenin-dependent autophagy. These results provide new insights into the mechanism of chronic periodontitis.

http://ift.tt/2BXVQ2G

Third molar agenesis as a potential marker for craniofacial deformities

Publication date: April 2018
Source:Archives of Oral Biology, Volume 88
Author(s): Clarissa Christina Avelar Fernandez, Christiane Vasconcellos Cruz Alves Pereira, Ronir Raggio Luiz, Italo M. Faraco, Mary L. Marazita, Maria Arnaudo, Flavia M. de Carvalho, Fernando E. Poletta, Juan C. Mereb, Eduardo E. Castilla, Iêda M. Orioli, Marcelo de Castro Costa, Alexandre Rezende Vieira
The identification of clinical patterns of tooth agenesis in individuals born with craniofacial deformities may be a useful tool for risk determination of these defects. We hypothesize that specific craniofacial deformities are associated with third molar agenesis.ObjectiveThe aim of this study was to identify if third molar agenesis could have a relation with other craniofacial structure alterations, such as cleft lip and palate, skeletal malocclusion, or specific growth patterns in humans.DesignData were obtained from 550 individuals ascertained as part of studies aiming to identify genetic contributions to oral clefts. 831 dental records of patients aged over eight years seeking orthodontic treatment were also included. SN-GoGn angle were used to classify the growth pattern (hypo-divergent, normal and hyper-divergent), and the ANB angle was used to verify the skeletal malocclusion pattern (Class I, II and III). Panoramic radiographs were used to determine third molar agenesis.ResultsA high frequency of third molar agenesis among individuals born with cleft lip with or without cleft palate (55%), as well as among their relatives (93.5%) was found. Third molar agenesis was not associated to skeletal malocclusion or growth pattern.ConclusionIt appears that third molar agenesis is associated with the disturbances that lead to cleft lip and palate.

http://ift.tt/2nG26rp

Structure, property, and function of sheepshead (Archosargus probatocephalus) teeth

Publication date: May 2018
Source:Archives of Oral Biology, Volume 89
Author(s): J.F. Deang, A.K. Persons, A.L. Oppedal, H. Rhee, R.D. Moser, M.F. Horstemeyer
ObjectivesThis paper studies A. probatocephalus teeth and investigates the mechanical properties and chemical composition of the enameloid and dentin.DesignNanoindentation tests with a max load of 1000 μN and X-ray Energy Dispersive Spectroscopy (EDS) were performed along the diameter of the polished sample. Microstructural analysis of the dentin tubules was performed from SEM images.ResultsFrom nanoindentation testing, the dentin of the sheepshead teeth has a nanoindentation hardness of 0.89 ± 0.21 (mean ± S.D.) GPa and a reduced Young's modulus of 23.29 ± 5.30 GPa. The enameloid of A. probatocephalus has a hardness of 4.36 ± 0.44 GPa and a mean reduced Young's modulus of 98.14 ± 6.91 GPa. Additionally, nanoindentation tests showed that the enameloid's hardness and modulus increased closer to the surface of the tooth. X-ray Energy Dispersive Spectroscopy (EDS) data further suggests that the gradient may be a result of the wt% fluoride within the enameloid, where an increase in fluoride results in an increase in reduced Young's modulus and hardness.ConclusionThe microstructural characterization of the number density and area of the dentin tubules were used to address the porosity effect in the dentin to achieve the experimentally validated microhardness. The mechanical properties of the sheepshead teeth were also compared with previous nanoindentation tests from other aquatic species. The sheepshead teeth exhibit a greater reduced Young's modulus and hardness compared to shark and piranha teeth.

Graphical abstract

http://ift.tt/2BWKFr3

Differentiation of stem cells from human deciduous and permanent teeth into spiral ganglion neuron-like cells

Publication date: April 2018
Source:Archives of Oral Biology, Volume 88
Author(s): Thanasup Gonmanee, Charoensri Thonabulsombat, Kutkao Vongsavan, Hathaitip Sritanaudomchai
ObjectiveStem cells from pulp tissue are a promising cell-based therapy for neurodegenerative patients based on their origin in the neural crest. The aim of this study was to differentiate and evaluate the ability of human dental pulp stem cells from permanent teeth (DPSC) and stem cells from human exfoliated deciduous teeth (SHED) to differentiate into spiral ganglion neurons.DesignAfter isolation and characterization of mesenchymal stem cell properties, DPSC and SHED were treated with the neurotrophins brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and glial cell-derived neurotrophic factor (GDNF). The differentiation was identified by immunostaining and qRT-PCR analysis of neuronal markers and measuring intracellular calcium activity.ResultsAfter 2 weeks of induction, morphological changes were observed in both DPSC and SHED. The differentiated cells expressed neuron-specific class III beta-tubulin, GATA binding protein 3 (GATA3) and tropomyosin receptor kinase B, protein markers of spiral ganglion neurons. These cells also showed upregulation of the genes encoding these proteins, namely GATA3 and neurotrophic receptor tyrosine kinase 2. Intracellular calcium dynamics that reflect neurotransmitter release were observed in differentiated DPSC and SHED.ConclusionThese results demonstrate that dental pulp stem cells from permanent and deciduous teeth can differentiate into spiral ganglion neuron-like cells.

http://ift.tt/2nG28zx

An in vitro study on the influence of viscosity and frequency of application of fluoride/tin solutions on the progression of erosion of bovine enamel

Publication date: Available online 3 February 2018
Source:Archives of Oral Biology
Author(s): Letícia Oba Sakae, Sávio José Cardoso Bezerra, Samira Helena João-Souza, Alessandra Buhler Borges, Idalina V. Aoki, Ana Cecília Côrrea Aranha, Taís Scaramucci
ObjectiveTo evaluate the influence of the viscosity and frequency of application of solutions containing sodium fluoride (NaF) and stannous chloride (SnCl2) on enamel erosion prevention.DesignBovine enamel specimens were randomly distributed into 12 groups (n = 10), according to the following study factors: solution (C: deionized water; F: 500 ppm F⁻; F + Sn: 500 ppm F⁻ + 800 ppm Sn²⁺); viscosity (low and high); and frequency of application (once and twice a day). Specimens were submitted to an erosive cycling model, consisting of 5 min immersion in 0.3% citric acid, followed by 60 min exposure to a mineral solution. This procedure was repeated 4x/day, for 5 days. Treatment with the experimental solutions was performed for 2 min, 1x/day or 2x/day. Enamel surface loss (SL) was determined by optical profilometry. Data were analyzed by 3-way ANOVA and Tukey tests (α = 0.05).ResultsThere were significant differences between the levels of the factor solution (p < 0.001), viscosity (p < .001) and in the interaction between solution and viscosity (p = 0.01). Regarding solution, the mean SL ± standard deviation for the groups was F + Sn (4.90 ± 1.12) < F (7.89 ± 1.19) < C (14.20 ± 1.69). High viscosity solutions demonstrated less SL than low viscosity; however, only when applied once a day (p < .001). Applying the solutions twice a day yielded lower SL than once a day, but only for the low viscosity solutions (p = 0.003).ConclusionsUnder the conditions of this short-term in vitro experiment, it could be concluded that increasing the viscosity of the oral rinse solutions reduced enamel loss by erosion; however, this effect was small and only observed when the solutions were applied once a day.

http://ift.tt/2BXkCA0

Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Δευτέρα 5 Φεβρουαρίου 2018

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