Αρχειοθήκη ιστολογίου

Κυριακή 11 Μαρτίου 2018

Successful therapy of ocular rosacea with topical ivermectin

Approximately 75% of cutaneous rosacea patients also suffer from an ocular involvement with blepharitis and meibomian gland dysfunction often presented as chalazia. Clinical symptoms are foreign body sensation, light sensitivity, burning and tearing.

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FOSB immunoreactivity in endothelia of epithelioid hemangioma (angiolymphoid hyperplasia with eosinophilia)

Background

Accurate distinction of epithelioid hemangioma (EH) from its malignant mimics is paramount but it remains challenging due to its wide morphological spectrum and lack of objective molecular markers. FOSB oncogenic activation was recently identified as a key event in endothelial proliferation. We sought to investigate the FOSB staining pattern in EH with angiolymphoid hyperplasia with eosinophilia morphology (EH-AHLE) and to evaluate its value in differential diagnosis of epithelioid vascular tumors.

Methods

From the authors' files, 15 representative cases of EH-ALHE were selected and evaluated for their FOSB immunostaining pattern. Other vascular proliferations which can be morphological mimics were also tested: epithelioid hemangioendothelioma (EHE) (5 cases) and epithelioid angiosarcoma (EAS) (5 cases).

Results

All 15 cases of EH-ALHE showed strong and homogeneous FOSB nuclear positivity in endothelial cells with ample cytoplasm and intracytoplasmic vacuoles. All cases of EHE and EAS lacked FOSB immunoreactivity or showed only incidental weak FOSB immunoreactivity in less than 5 nuclei per lesion.

Conclusions

FOSB immunohistochemistry is sensitive in the diagnosis of EH-ALHE, and allows differentiation from its histological mimics. An immunohistochemical panel including not only pan-cytokeratin AE1/AE3 and endothelial markers, but also FOSB, helps in the diagnosis of epithelioid vascular tumors.



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Society for Neuroscience 2017 Satellite Symposium on Feeding and Swallowing: From Neural Mechanisms to Rehabilitation



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Impact of socioeconomic status on survival for patients with anal cancer

BACKGROUND

Although outcomes for patients with squamous cell carcinoma of the anus (SCCA) have improved, the gains in benefit may not be shared uniformly among patients of disparate socioeconomic status. In the current study, the authors investigated whether area-based median household income (MHI) is predictive of survival among patients with SCCA.

METHODS

Patients diagnosed with SCCA from 2004 through 2013 in the Surveillance, Epidemiology, and End Results registry were included. Socioeconomic status was defined by census-tract MHI level and divided into quintiles. Multivariable Cox proportional hazards models and logistic regression were used to study predictors of survival and radiotherapy receipt.

RESULTS

A total of 9550 cases of SCCA were included. The median age of the patients was 58 years, 63% were female, 85% were white, and 38% were married. In multivariable analyses, patients living in areas with lower MHI were found to have worse overall survival and cancer-specific survival (CSS) compared with those in the highest income areas. Mortality hazard ratios for lowest to highest income were 1.32 (95% confidence interval [95% CI], 1.18-1.49), 1.31 (95% CI, 1.16-1.48), 1.19 (95% CI, 1.06-1.34), and 1.16 (95% CI, 1.03-1.30). The hazard ratios for CSS similarly ranged from 1.34 to 1.22 for lowest to highest income. Older age, black race, male sex, unmarried marital status, an earlier year of diagnosis, higher tumor grade, and later American Joint Committee on Cancer stage of disease also were associated with worse CSS. Income was not found to be associated with the odds of initiating radiotherapy in multivariable analysis (odds ratio of 0.87 for lowest to highest income level; 95% CI, 0.63-1.20).

CONCLUSIONS

MHI appears to independently predict CSS and overall survival in patients with SCCA. Black race was found to remain a predictor of SCCA survival despite controlling for income. Further study is needed to understand the mechanisms by which socioeconomic inequalities affect cancer care and outcomes. Cancer 2018. © 2018 American Cancer Society.



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20Q: Outcome Measures in Clinical Practice

A review of the definition and purpose of outcome measures in audiology, and a discussion of a new outcome measure assessing hearing aid benefit.

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Photodynamic therapy: Promoting in vitro efficacy of photodynamic therapy by liposomal formulations of a photosensitizing agent

Objective

A relatively low level of lysosomal photodamage has been shown capable of promoting the efficacy of photodamage simultaneously or subsequently directed to mitochondrial/ER sites. The procedure has hitherto involved the use of two photosensitizing agents that require irradiation at two different wavelengths and different formulation techniques. This, together with different pharmacokinetic profiles of the photosensitizers, adds a layer of complexity to a protocol that we have sought to circumvent. In this study, liposomal formulations were used to direct photodamage created by benzoporphyrin derivative (BPD, Verteporfin) to lysosomes, mitochondria and the ER. This resulted in the development of an optimal targeting profile using a single agent and a single wavelength of activating irradiation.

Materials/Methods

These studies were carried out in monolayer cultures of OVCAR5 tumor cells. BPD localization was modified by lipid anchoring and formulation in liposomes, and was assessed by fluorescence microscopy. Irradiation was carried out at 690 ± 10 nm with photodamage assessed also using fluorescent probes and microscopy.

Results

BPD normally localizes in a wide variety of sub-cellular loci that include both mitochondria and the ER, but lysosomes are spared from photodamage. Using a liposomal formulation containing BPD anchored to a lipid resulted in the targeting of lysosomes. A mixture of liposomes containing "free" and "anchored" BPD was shown to significantly promote photokilling. Eliminating cholesterol from the formulation of the anchored product enhanced lysosomal photodamage; prior studies had revealed that excess cholesterol can have a cytoprotective effect when lysosomes are the PDT target.

Discussion

The ability of a liposomal formulation to change localization patterns permits directing photodynamic therapy toward specific sub-cellular loci, thereby promoting photokilling. Incorporating chemotherapeutic agents into such formulations could represent a logical next step in assessing the ability of directed photodamage to enhance tumor eradication. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.



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EUROPEAN SPINE JOURNAL MAX AEBI AWARD FOR CLINICAL SCIENCE 2016/2017



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GRAMMER EUROPEAN SPINE JOURNAL AWARD FOR BASIC SCIENCE AND APPLIED RESEARCH 2016/2017



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Knowledge, attitudes, and first-aid measures about epilepsy among primary school teachers in northern Iran

Objective

To assess knowledge, attitudes, and first-aid measures about epilepsy among primary school teachers.

Method

This cross-sectional study was conducted with participation of 342 primary school teachers during September 2016 to January 2017 in cities of Babol and Qaem-Shahr in Mazandaran Province in northern Iran. Primary schools were selected using simple random sampling. Data were collected through interviews using a structured questionnaire. The knowledge section included general knowledge, causes, symptoms, seizure triggers, first-aid measures, and recommended treatments. The Likert scale was used for the attitudes section. Answers about first-aid measures were categorized as helpful or harmful.

Results

The level of total knowledge score of 25 (7.7%) teachers was very high, 140 (43.3%) high, 141 (43.8%) moderate, and 17 (5.2%) low. The mean score about general knowledge was as follows: 6.1 (1.9), range = 0-9; causes 6.3 (1.9), range = 0-10; symptoms of seizures 8.5 (2.5), range = 0-12; and first-aid measures 6.8 (2.0), range = 0-11. Some 83% knew not taking anticonvulsants regularly could trigger seizures, and all teachers said a person with epilepsy should go see a physician. Attitudes were generally positive except for marriage and having children. The level of first-aid measures score of 8 (7.2) teachers was very high, 79 (70.5) high, 25 (22.3) low. Teachers with teaching experience at special schools took more helpful measures

Conclusions

The knowledge of teachers about epilepsy was insufficient, attitudes toward people with epilepsy were generally positive, and first-aid measures at the last witnessed seizure were fairly helpful. Having teaching experience in special schools had a positive influence over knowledge and taking appropriate first-aid measure at time of the last witnessed seizure.



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Evaluation of serum miR-191-5p, miR-24-3p, miR-128-3p, and miR-376c-3 in multiple sclerosis patients

Background

Biomarkers that could be used in early diagnosis of multiple sclerosis (MS), segregation of disease subtypes, and discrimination of the aggressive disease course from the benign one are urgently needed.

Objective

The aim of this study was to investigate the specificity of circulating microRNAs: miR-191-5p, miR-128-3p, miR-24-3p, and miR-376c-3p in MS and evaluate their association with disease activity and disability progression.

Methods

The expressions of circulating miRNAs were studied in serum of 100 subjects (53 relapsing-remitting (RRMS), 20 primary progressive (PPMS), and 27 controls), using miScript serum miRNA RT-PCR assay techniques.

Results

In comparison with controls, miR-191-5p and miR-24-3p were overexpressed in RRMS and PPMS, with no differences between the subtypes. miR-24-3p correlated positively with the disability progression index in the combined group of all patients with MS. miR-128-3p showed tendency toward the predominant expression in PPMS and correlated positively with the annual relapse rate in RRMS. miR-376c-3p expression levels did not differ between the groups, and no associations were found to clinical parameters.

Conclusion

This study highlighted the connection of circulating miRNAs to MS. miR-24-3p and miR-128-3p showed a tendency of association with disability accumulation and disease activity, respectively. Further studies should evaluate their suitability for clinical use.



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Pseudobulbar affect as a negative prognostic indicator in amyotrophic lateral sclerosis

Objective

To evaluate whether the presence of pseudobulbar affect (PBA) in an early stage of the disease influences survival in a population-based incident cohort of amyotrophic lateral sclerosis (ALS).

Methods

Incident ALS cases, diagnosed according to El Escorial criteria, were enrolled from a prospective population-based registry in Puglia, Southern Italy. The Center for Neurologic Study-Lability Scale (CNS-LS), a self-administered questionnaire, was used to evaluate PBA. Total scores range from 7 to 35. A score ≥13 was used to identify PBA. Cox proportional hazard models were used for survival analysis. The modified C-statistic for censored survival data was used for models' discrimination. RECursive Partitioning and AMalgamation (RECPAM) analysis was used to identify subgroups of patients with different patterns of risk, depending on baseline characteristics.

Results

We enrolled 94 sporadic ALS, median age of 64 years (range: 26-80). At the censoring date, 65 of 94 (69.2%), 39 of 60 (65.0%), and 26 of 34 (76.5%) patients reached the outcome (tracheotomy/death), in the whole, non-PBA and in the PBA groups, respectively. Kaplan-Meier survival curves for the two subgroups were not significantly different (log-rank test: 1.3, P = .25). The discrimination ability of a multivariable model with demographic and clinical variables of interest was not improved by adding PBA. In the RECPAM analysis, ALSFRSr and the total score of CNS-LS scale (</≥10) were the most important variables for differentiating all risk categories.

Conclusions

These preliminary results underlie that the presence of PBA at entry negatively influences survival in a specific subgroup of patients with ALS characterized by less functional impairment.



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Cover Image

Thumbnail image of graphical abstract

The cover image, by Yuto Uchida et al., is based on the Clinical Commentary Stiripentol for the treatment of super-refractory status epilepticus with cross-sensitivity, DOI: 10.1111/ane.12888.



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Issue Information



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Adjunctive perampanel for partial-onset seizures



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Society for Neuroscience 2017 Satellite Symposium on Feeding and Swallowing: From Neural Mechanisms to Rehabilitation



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Fracture strength of zirconia implant abutments on narrow diameter implants with internal and external implant abutment connections: A study on the titanium resin base concept

Abstract

Background

There is limited knowledge regarding the strength of zirconia abutments with internal and external implant abutment connections and zirconia abutments supported by a titanium resin base (Variobase, Straumann) for narrow diameter implants.

Objectives

To compare the fracture strength of narrow diameter abutments with different types of implant abutment connections after chewing simulation.

Material and methods

Hundred and twenty identical customized abutments with different materials and implant abutment connections were fabricated for five groups: 1-piece zirconia abutment with internal connection (T1, Cares-abutment-Straumann BL-NC implant, Straumann Switzerland), 1-piece zirconia abutment with external hex connection (T2, Procera abutment-Branemark NP implant, Nobel Biocare, Sweden), 2-piece zirconia abutments with metallic insert for internal connection (T3, Procera abutment-Replace NP implant, Nobel Biocare), 2-piece zirconia abutment on titanium resin base (T4, LavaPlus abutment-VarioBase-Straumann BL-NC implant, 3M ESPE, Germany) and 1-piece titanium abutment with internal connection (C, Cares-abutment-Straumann BL-NC implant, Straumann, Switzerland). All implants had a narrow diameter ranging from 3.3 to 3.5 mm. Sixty un-restored abutments and 60 abutments restored with glass-ceramic crowns were tested. Mean bending moments were compared using ANOVA with p-values adjusted for multiple comparisons using Tukey's procedure.

Results

The mean bending moments were 521 ± 33 Ncm (T4), 404 ± 36 Ncm (C), 311 ± 106 Ncm (T1) 265 ± 22 Ncm (T3) and 225 ± 29 (T2) for un-restored abutments and 278 ± 84 Ncm (T4), 302 ± 170 Ncm (C), 190 ± 55 Ncm (T1) 80 ± 102 Ncm (T3) and 125 ± 57 (T2) for restored abutments. For un-restored abutments, C and T4 had similar mean bending moments, significantly higher than those of the three other groups (p < .05). Titanium abutments (C) had significantly higher bending moments than identical zirconia abutments (T1) (p < .05). Zirconia abutments (T1) with internal connection had higher bending moments than zirconia abutments with external connection (T2) (p < .05). For all test groups, the bending moments were significantly reduced when restored with all-ceramic crowns.

Conclusions

For narrow diameter abutments, the fracture strength of 2-piece internal connected zirconia abutments fixed on titanium resin bases was similar to those obtained for 1-piece titanium abutments. Narrow diameter zirconia abutments with internal connection exhibited higher fracture strength than zirconia abutments with an external connection. Titanium abutments with an internal connection were significantly stronger than identical zirconia abutments.



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Crosstalk between ovarian cancer cells and macrophages via periostin promotes macrophage recruitment

Abstract

Tumor-associated macrophages (TAMs) contribute to tumor progression, but it is not clear how they are recruited to tumor sites. Here we showed that periostin (POSTN) was present at high levels in ovarian cancer ascetic fluids and was correlated with CD163+TAMs. The high POSTN level and macrophage infiltration were inversely associated with relapse-free survival for ovarian cancer patients. In vitro studies showed that co-culture with macrophages significantly increased POSTN production in ovarian cancer cells. Further investigation found that POSTN production in ovarian cancer cells was promoted by TGF-β generated by macrophages. Moreover, siRNA of POSTN and POSTN neutralizing antibody treatment demonstrated that ovarian cancer cell-derived POSTN promoted the recruitment of macrophages and modulated their cytokine secretion profile. Collectively, these data demonstrated that POSTN was an important factor for macrophage recruitment in tumor microenvironment, involved in the interactions between macrophages and ovarian cancer cells.

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Translucency of Zirconia Ceramics before and after Artificial Aging

Abstract

Purpose

The aging of zirconia ceramics (Y-TZP) is associated with tetragonal to monoclinic phase transformation. This change in microstructure may affect the optical properties of the ceramic. This study examines the effect of aging on the translucency of different zirconia materials.

Materials and Methods

120 disc-shaped specimens were fabricated from four zirconia materials: Cercon ht white, BruxZir Solid Zirconia, Zenostar T0, Lava Plus (n = 30 per group). Accelerated aging was performed in a steam autoclave (134°C, 0.2 MPa, 5 hours). CIELab coordinates (L*, a*, b*) and luminous reflectance (Y) were measured with a spectrophotometer before and after aging. Contrast ratio (CR) and translucency parameter (TP) were calculated from the L*, a*, b*, and Y tristimulus values. The general linear model (Bonferroni adjusted) was used to compare both parameters before and after aging, as well as between the different zirconia materials (p ≤ 0.05).

Results

CR and TP differed significantly before and after aging in all groups tested. Before aging, Zenostar T showed the highest and Lava Plus showed the lowest translucency. After aging, Cercon ht and Zenostar T showed the highest and BruxZir and Lava Plus the lowest translucency.

Conclusions

Aging reduced the translucency in all specimens tested. Furthermore, translucency differed between the zirconia brands tested. Nevertheless, the differences were below the detectability threshold of the human eye. The aging process can influence the translucency and thus the esthetic outcome of zirconia restorations; however, the changes in translucency were minimal and probably undetectable by the human eye.



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A phase 1 dose-escalation study of veliparib with bimonthly FOLFIRI in patients with advanced solid tumours

A phase 1 dose-escalation study of veliparib with bimonthly FOLFIRI in patients with advanced solid tumours

A phase 1 dose-escalation study of veliparib with bimonthly FOLFIRI in patients with advanced solid tumours, Published online: 12 March 2018; doi:10.1038/s41416-018-0003-3

A phase 1 dose-escalation study of veliparib with bimonthly FOLFIRI in patients with advanced solid tumours

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Identification of selective inhibitors for diffuse-type gastric cancer cells by screening of annotated compounds in preclinical models

Identification of selective inhibitors for diffuse-type gastric cancer cells by screening of annotated compounds in preclinical models

Identification of selective inhibitors for diffuse-type gastric cancer cells by screening of annotated compounds in preclinical models, Published online: 12 March 2018; doi:10.1038/s41416-018-0008-y

Identification of selective inhibitors for diffuse-type gastric cancer cells by screening of annotated compounds in preclinical models

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Body mass index throughout adulthood, physical activity, and risk of multiple myeloma: a prospective analysis in three large cohorts

Body mass index throughout adulthood, physical activity, and risk of multiple myeloma: a prospective analysis in three large cohorts

Body mass index throughout adulthood, physical activity, and risk of multiple myeloma: a prospective analysis in three large cohorts, Published online: 12 March 2018; doi:10.1038/s41416-018-0010-4

Body mass index throughout adulthood, physical activity, and risk of multiple myeloma: a prospective analysis in three large cohorts

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Phase II study of everolimus (RAD001) monotherapy as first-line treatment in advanced biliary tract cancer with biomarker exploration: the RADiChol Study

Phase II study of everolimus (RAD001) monotherapy as first-line treatment in advanced biliary tract cancer with biomarker exploration: the RADiChol Study

Phase II study of everolimus (RAD001) monotherapy as first-line treatment in advanced biliary tract cancer with biomarker exploration: the RADiChol Study, Published online: 12 March 2018; doi:10.1038/s41416-018-0021-1

Phase II study of everolimus (RAD001) monotherapy as first-line treatment in advanced biliary tract cancer with biomarker exploration: the RADiChol Study

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Adjuvant Bisphosphonate Therapy in Postmenopausal Breast Cancer

Opinion statement

Bone health and breast cancer are two connected subjects, because breast cancer patients have a higher prevalence of osteopenia/osteoporosis and reduced bone health parameters than healthy woman of the same age. Therefore, the positive effect of adjuvant bisphosphonate therapy plays an important role in breast cancer treatment. Several randomized trials have studied bisphosphonates in the adjuvant setting in postmenopausal woman and demonstrated their potential to prevent treatment-induced bone loss. The prevention of fractures and the subsequent preservation of patients' quality of life are important arguments for the use of adjuvant bisphosphonates in postmenopausal breast cancer patients. In addition, trials of adjuvant bone-targeted agents showed a reduction of recurrences in and outside bone and an improved outcome in patients treated with bisphosphonates.



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Testing the Timing: Time Factor in Radiation Treatment for Head and Neck Cancers

Opinion statement

Overall radiation treatment time has long been recognized as an important factor in head and neck tumor control. The concern of tumor growth in waiting time either before starting radiotherapy or during treatment is substantial given its negative impact on clinical outcome. There is an overwhelming evidence that increasing the time to initiate treatment increases the tumor burden and worsens the prognosis. This effect is more pronounced especially in patients with an early stage cancer disease. Delay in treatment initiation is contributed by both health care- and patient-related factors. Health care-related factors include advancement in diagnostic modalities and transfer of patient to academic health care centers accompanied by delayed referrals and long-awaited appointments. Patient-related factors include delayed reporting time and socioeconomic factors. An efficient transition of care along with access of cancer care modalities to community health care centers will not only improve the quality of care in secondary health care centers but also help decrease the patient burden in tertiary centers. A quick and well-structured multidisciplinary appointment program is fundamental in shortening the time required for patient referrals, thus increasing the optimal survival time for Head and Neck cancer patients with early initiation of treatment.



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Shoulder Dynamic Control Ratio and Rotation Range of Motion in Female Junior Elite Handball Players and Controls

imageObjective: To compare glenohumeral range of motion and shoulder rotator muscle strength in healthy female junior elite handball players and controls. Design: Cross-sectional case–control study. Setting: Sports medical center. Participants: Forty elite female handball players and 30 controls active in nonoverhead sports participated in this study. Main Outcome Measures: Passive external rotator (ER), internal rotator (IR), and total range of motion (TROM) of the dominant and nondominant arm were examined with a goniometer. An isokinetic dynamometer was used to evaluate concentric and eccentric rotator muscle strength at 60 and 120 degrees/s with dynamic control ratio (DCR = ERecc:IRcon) as the main outcome parameter. Results: Except for the ER range of motion in the nondominant arm, no significant differences were found between groups for IR, ER of the dominant arm, and the TROM. Within the handball group, the side-to-side difference for IR of the dominant arm was −1.4 degrees. The ER and the TROM of the dominant arm were significantly larger, 6.3 and 4.9 degrees, respectively. For both groups, the DCR values were above 1 and no significant differences were found between the dominant and nondominant arm. The DCR values in the handball group were significantly lower than in the control group. Conclusions: Based on the adopted definitions for muscle imbalance, glenohumeral internal range of motion deficit and TROM deficit our elite female handball players seem not at risk for shoulder injuries. Prospective studies are needed to support the belief that a DCR below 1 places the shoulder at risk for injury.

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AMSSM Oral Research Poster Presentations

No abstract available

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MRI Evidence of Neuropathic Changes in Former College Football Players

imageObjective: To examine effects of participating in collegiate football on neural health several years after retirement. We hypothesized that relative cortical thinning and loss of white matter integrity would be observed in former players. Design: Former NCAA Division I football players were compared with demographically similar track-and-field athletes with regard to cortical thickness and white matter integrity. Setting: Participants participated in MRI scans at the Center for Imaging Research at the University of Cincinnati. Participants: Eleven former football players and 10 demographically similar track-and-field athletes. Main Outcome Measures: Normalized cortical thickness was compared between groups using 2-tailed Student t test. As a secondary analysis, Spearman correlation coefficient was calculated between cortical thickness and number of concussions. Fractional anisotropy for regions-of-interest placed in frontal white matter tracts and internal capsule were compared between groups using 2-tailed Student t test. Results: Football players showed significantly lower cortical thickness within portions of both the frontal and temporal cortex. Affected frontal regions included left frontal pole and right superior frontal gyrus. Affected temporal regions included portions of the superior temporal gyrus, left inferior temporal gyrus, and right middle and superior temporal gyri. Cortical thickness inversely correlated with number of reported concussions over most of these regions. In addition, fractional anisotropy was lower in the right internal capsule of former football players, relative to controls. Conclusions: These findings suggest that at least some consequences of high-level collegiate football play persist even after the cessation of regular head blows. Longer-term studies are warranted to examine potential cognitive and functional implications of sustained cortical atrophy.

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Screening Tool to Determine Risk of Having Muscle Dysmorphia Symptoms in Men Who Engage in Weight Training at a Gym

imageObjective: Although 2 screening tests exist for having a high risk of muscle dysmorphia (MD) symptoms, they both require a long time to apply. Accordingly, we proposed the construction, validation, and implementation of such a test in a mobile application using easy-to-measure factors associated with MD. Design: Cross-sectional observational study. Setting: Gyms in Alicante (Spain) during 2013 to 2014. Participants: One hundred forty-one men who engaged in weight training. Assessment of Risk Factors: The variables are as follows: age, educational level, income, buys own food, physical activity per week, daily meals, importance of nutrition, special nutrition, guilt about dietary nonadherence, supplements, and body mass index (BMI). A points system was constructed through a binary logistic regression model to predict a high risk of MD symptoms by testing all possible combinations of secondary variables (5035). The system was validated using bootstrapping and implemented in a mobile application. Main Outcome Measures: High risk of having MD symptoms (Muscle Appearance Satisfaction Scale). Results: Of the 141 participants, 45 had a high risk of MD symptoms [31.9%, 95% confidence interval (CI), 24.2%-39.6%]. The logistic regression model combination providing the largest area under the receiver operating characteristic curve (0.76) included the following: age [odds ratio (OR) = 0.90; 95% CI, 0.84-0.97, P = 0.007], guilt about dietary nonadherence (OR = 2.46; 95% CI, 1.06-5.73, P = 0.037), energy supplements (OR = 3.60; 95% CI, 1.54-8.44, P = 0.003), and BMI (OR = 1.33, 95% CI, 1.12-1.57, P

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The Influence of Heavier Football Helmet Faceguards on Head Impact Location and Severity

imageObjective: To determine whether players with heavier faceguards have increased odds of sustaining top of the head impacts and head impacts of higher severity. Design: Cohort study. Setting: On-field. Participants: Thirty-five division I collegiate football players. Interventions: Faceguard mass was measured. Head impact location and severity (linear acceleration [gravity], rotational acceleration [radian per square second], and Head Impact Technology severity profile [unitless]) were captured for 19 379 total head impacts at practices using the Head Impact Telemetry System. Main Outcome Measures: Players' faceguards were categorized as either heavier (>480 g) or lighter (≤480 g) using a median split. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed for sustaining top of the head impacts between faceguard groups using a random intercepts generalized logit model. We compared head impact severity between groups using random intercepts general linear models (α = 0.05). Player position was included in all models. Results: Overall, the 4 head impact locations were equally distributed across faceguard groups (F(3,26) = 2.16, P = 0.117). Football players with heavier faceguards sustained a higher proportion impacts to the top of the head (24.7% vs 17.5%) and had slightly increased odds of sustaining top (OR, 1.72; 95% CI, 1.01-2.94) head impacts rather than front of the head impacts. Conclusions: Football players wearing heavier faceguards might be slightly more prone to sustaining a higher proportion of top of the head impacts, suggesting that greater faceguard mass may make players more likely to lower their head before collision. Individuals involved with equipment selection should consider the potential influence of faceguard design on head impact biomechanics when recommending the use of a heavier faceguard.

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Consequences of Traumatic Brain Injury in Professional American Football Players: A Systematic Review of the Literature

imageObjective: The purpose of this study was to systematically review the literature for the consequences Traumatic brain injury (TBI) has on cognitive, psychological, physical, and sports-related functioning in professional American Football players. Data Sources: We performed a systematic search in 2 databases, PubMed and SPORTDiscus, to obtain literature from January 1990 to January 2015. To be eligible for inclusion, a study had to examine the relationship between TBI and the consequences for several aspects of functioning in professional American football players older than 18 years. Methodological quality was assessed using a 5-item checklist which assessed selection bias, information bias, and correct reporting of the population and exposure characteristics. Main Results: The search yielded 21 studies that met our inclusion criteria. An evidence synthesis was performed on the extracted data and resulted in 5 levels of evidence. The evidence synthesis revealed that there is strong evidence that concussions are associated with late-life depression and short-term physical dysfunctions. Evidence for the relationship between concussion and impaired sports-related function, prolonged reaction time, memory impairment, and visual-motor speed was inconclusive. Moderate evidence was found for the association between TBI and mild cognitive impairment (MCI), and limited evidence was found for the association between TBI and executive dysfunction. Conclusions: There is strong evidence that a history of concussion in American football players is associated with depression later in life and short-term physical dysfunctions. Also cognitive dysfunctions such as MCI are seen in older players with a history of TBI. These results provide input for actions to prevent TBI and their consequences in (retired) American football players.

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Collegiate Student Athletes With History of ADHD or Academic Difficulties Are More Likely to Produce an Invalid Protocol on Baseline ImPACT Testing

imageObjective: Attention deficit hyperactivity disorder (ADHD) and other academically-relevant diagnoses have been suggested as modifiers of neurocognitive testing in sport-related concussion, such as Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT). These preexisting conditions may suppress ImPACT scores to the extent that they are indistinguishable from low scores because of poor effort. The present study hypothesized that student athletes with history of ADHD or academic difficulties produce lower ImPACT composite scores and are more likely to produce invalid protocols than those without such conditions. Design: Cross-sectional study. Setting: Midsized public university. Participants: Nine hundred forty-nine National College Athletic Association athletes (average age = 19.2 years; 6.8% ADHD, 5.6% Academic Difficulties, 2.0% comorbid ADHD/Academic Difficulties). Independent Variables: Three seasons of baseline ImPACT protocols were analyzed. Student athletes were grouped using self-reported histories of ADHD or academic difficulties taken from ImPACT demographic questions. Dependent Variables: ImPACT composite scores and protocol validity. Results: Student athletes in the academic difficulties and comorbid groups performed worse on ImPACT composite scores (Pillai's Trace = 0.05), though this pattern did not emerge for those with ADHD. Student athletes with comorbid history were more likely to produce an invalid baseline (10.5% invalid) (χ2 (2) = 11.08, P = 0.004). Those with ADHD were also more likely to produce an invalid protocol (7.7% invalid, compared with 2.6% in student athletes with no history) (χ2 (2) = 10.70, P = 0.005). Conclusions: These findings suggest that student athletes reporting comorbid histories or histories of academic difficulties alone produce lower ImPACT composite scores, and that those with comorbid histories or histories of ADHD alone produce invalid protocol warnings more frequently than student athletes without such histories. Future studies should further examine invalid score thresholds on the ImPACT, especially in student athletes with conditions that may influence test performance. Clinical Relevance: Student athletes with history of ADHD or academic difficulties may more frequently fall below validity score thresholds, suggesting caution in interpreting test performance.

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BTrackS Balance Test for Concussion Management is Resistant to Practice Effects

imageObjective: Recent guidelines advocate for ongoing balance testing in the assessment of management of concussion injuries. This study sought to determine whether the Balance Tracking System (BTrackS) provides stable balance results over repeated administration and, thus, is a reliable tool for concussion management. Design: Repeated measures and test–retest reliability. Setting: University Biomechanics Laboratory. Participants: Random sample of 20 healthy young adults. Interventions: Force plate balance testing using BTrackS on days 1, 3, 8, and 15. Main Outcome Measures: Practice-induced changes in the average center of pressure excursion over 4 repeated administrations of the BTrackS Balance Test (BBT). Test–retest reliability of center of pressure excursion from day 1 to day 15. Results: No significant practice-induced balance differences were found across testing days (P > 0.4), and test–retest reliability of the BBT was excellent from day 1 to day 15 (R 0.92). Conclusions: These findings indicate that the BBT does not elicit a practice effect over repeat administrations. BTrackS provides excellent reliability and objectivity, which can increase clinician accuracy when monitoring sport-related concussions.

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Investigation of the Rosenbaum Concussion Knowledge and Attitudes Survey in Collegiate Athletes

imageObjective: The purpose of this study is to determine whether the Rosenbaum Concussion Knowledge and Attitudes Survey (RoCKAS) is an appropriate outcome measure to assess knowledge and attitudes toward concussion in collegiate student-athletes as determined through validity and reliability testing. Study Design: Convenience study. Setting: The researcher recruited all athletic teams at a Division III National Collegiate Athletic Association institution. Participants: Four hundred thirty-three collegiate student-athletes, 18 years of age or older, from a variety of sports took part in this study. As the validity of RoCKAS has never been established for the target population, this study randomly split respondents into 2 studies. Interventions: Participants in this study completed the RoCKAS during preseason meetings before concussion education. The primary researcher was not present during the completion of the survey to allow participants to answer honestly without concern of coercion. Main Outcome Measures: A paper-based Rosenbaum Concussion Knowledge and Attitudes Survey. Results: The Concussion Knowledge Index (CKI) was distributed in 2 cluster constructs and identified variables of low and high difficulty. Multivariate statistical analysis of the Concussion Attitude Index (CAI) explains 68.79% of the total variance. The Confirmatory Factor Analysis did not confirm the hypothesis that similar constructs can be found between data sets ( JOURNAL/cjspm/04.02/00042752-201803000-00005/math_5MM1/v/2018-03-08T125547Z/r/image-tiff = 207.902; consistent akaike information criterion = 391.550; root mean square error of approximation = 0.125, and goodness of fit index = 0.868). Conclusions: The CKI is a valid and reliable measure in collegiate student-athletes. However, the results of the Confirmatory Factor Analysis indicated a poor model fit and improper correlations between attitude items. Therefore, the CAI may not be a sound outcome measure of collegiate student-athlete's attitudes toward concussions.

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AMSSM Research Podium Presentations

No abstract available

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Genetics Influence Neurocognitive Performance at Baseline but Not Concussion History in Collegiate Student-Athletes

imageObjective: This study investigates 4 single-nucleotide polymorphisms [Apolipoprotein E (APOE), APOE promoter, catechol-O-methyl transferase (COMT), and dopamine D2 receptor] that have been implicated in concussion susceptibility and/or cognitive ability in collegiate student-athletes. Design: Cross-sectional study. Setting: Neuroscience laboratory at Elon University. Participants: Two hundred fifty division I collegiate student-athletes (66 women, 184 men) from various sports. Intervention: All participants completed Immediate Postconcussion Assessment and Cognitive Testing (ImPACT) testing at baseline concussion testing and had a buccal swab taken for DNA for genotyping. Main Outcome Measures: Self-reported history of concussions and neurocognitive performance were taken from ImPACT. Results: Individuals carrying an ε4 allele in their APOE gene had a significantly slower reaction time (P = 0.001). Individuals homozygous for the Val allele of the COMT gene showed significantly worse impulse control scores (P = 0.014). None of the genotypes were able to predict self-reported concussion history in collegiate student-athletes. Conclusions: These results indicate that certain genotypes may influence performance on cognitive testing at baseline and that the APOE genotypes may not influence concussion susceptibility as suggested by past studies.

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Reliability and Validity of Athletes Disability Index Questionnaire

imageObjective: The purpose of this study was to evaluate validity and reliability of a new proposed questionnaire for assessment of functional disability in athletes with low back pain (LBP). Design: Validity and reliability study. Setting: Elite athletes participating in different fields of sports. Participants: Participants were 165 male and female athletes (between 12 and 50 years old) with LBP. Interventions: Athlete Disability Index (ADI) Questionnaire which is developed by the authors for assessing LBP-related disability in athletes, Oswestry Disability Index (ODI), and the Roland-Morris Disability Questionnaire (RDQ). Main Outcome Measures: Self-reported responses were collected regarding LBP-related disability through ADI, ODI, and RDQ. Results: The test–retest reliability was strong, and intraclass correlation value ranged between 0.74 and 0.94. The Cronbach alpha coefficient value of 0.91 (P

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No Seasonal Changes in Cognitive Functioning Among High School Football Athletes: Implementation of a Novel Electrophysiological Measure and Standard Clinical Measures

imageObjective: To evaluate neuroelectric and cognitive function relative to a season of football participation. Cognitive and neuroelectric function declines are hypothesized to be present in football athletes. Design: Observational. Setting: Athletic fields and research laboratory. Patients (or Participants): Seventy-seven high school athletes (15.9 + 0.9 years, 178.6 + 7.2 cm, 74.4 + 14.7 kg, and 0.8 + 0.8 self-reported concussions) participating in football (n = 46) and noncontact sports (n = 31). Interventions (or Assessment of Risk Factors): All athletes completed preseason, midseason, and postseason assessments of cognitive and neuroelectric function, self-reported symptoms, and quality of life. All athletes participated in their respective sports without intervention, while head impact exposure in football athletes was tracked using the Head Impact Telemetry System. Main Outcome Measures: Cognitive performance was based on Cogstate computerized cognitive assessment tool processing speed, attention, learning, working memory speed, and working memory accuracy scores. ElMindA brain network activation amplitude, synchronization, timing and connectivity brain network activation scores demarcated neuroelectric performance. Quality of life was assessed on the Health Behavior Inventory and Satisfaction with Life Scale and symptoms on the SCAT3 inventory. Results: Football and control sport athletes did not show declines in cognitive or neuroelectric function, quality-of-life measures, or symptom reports across a season of sport participation. Conclusions: These findings refute the notion that routine football participation places athletes at risk for acute cognitive declines. The lack of impairment may be associated with no association with head impacts and cognitive function, increased physical activity offsetting any declines, and/or test sensitivity. How these findings are associated with long-term cognitive function is unknown.

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Sensitivity and Specificity of the Modified Balance Error Scoring System in Concussed Collegiate Student Athletes

imageObjective: To assess the efficacy of the modified Balance Error Scoring System (mBESS) compared with the Balance Error Scoring System (BESS) in an acutely concussed population. Design: Prospective observational study. Setting: University athletic training room. Patients: Thirty-five collegiate student-athletes (18 Female, 18.9 ± 0.8 year old, height: 1.71 ± 0.12 m, weight: 76.3 ± 24.1 kg) with diagnosed concussions and baseline BESS/mBESS tests. Interventions: All participants completed the BESS and mBESS on the day after the concussion (acute) and were retested daily until their BESS score achieved baseline value (recovery). Main Outcome Measures: The number of errors committed during the BESS and mBESS at each time point were recorded. The sensitivity and specificity of the BESS and mBESS compared with the baseline test was calculated for acute and recovery as well as the mBESS compared with the BESS. Results: At acute, the sensitivity of the BESS and mBESS were 60.0% and 71.4%, respectively. Relative to mBESS baseline, 60% of participants were misclassified at either acute or recovery. Conclusions: The mBESS had higher sensitivity at acute and identified lingering deficits at BESS recovery. Use of the mBESS is likely to produce different results than the BESS; however, the clinical implications of this warrant further investigation.

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Vision and Vestibular System Dysfunction Predicts Prolonged Concussion Recovery in Children

imageObjective: Up to one-third of children with concussion have prolonged symptoms lasting beyond 4 weeks. Vision and vestibular dysfunction is common after concussion. It is unknown whether such dysfunction predicts prolonged recovery. We sought to determine which vision or vestibular problems predict prolonged recovery in children. Design: A retrospective cohort of pediatric patients with concussion. Setting: A subspecialty pediatric concussion program. Patients (or Participants): Four hundred thirty-two patient records were abstracted. Assessment of Risk Factors: Presence of vision or vestibular dysfunction upon presentation to the subspecialty concussion program. Main Outcome Measures: The main outcome of interest was time to clinical recovery, defined by discharge from clinical follow-up, including resolution of acute symptoms, resumption of normal physical and cognitive activity, and normalization of physical examination findings to functional levels. Results: Study subjects were 5 to 18 years (median = 14). A total of 378 of 432 subjects (88%) presented with vision or vestibular problems. A history of motion sickness was associated with vestibular dysfunction. Younger age, public insurance, and presence of headache were associated with later presentation for subspecialty concussion care. Vision and vestibular problems were associated within distinct clusters. Provocable symptoms with vestibulo-ocular reflex (VOR) and smooth pursuits and abnormal balance and accommodative amplitude (AA) predicted prolonged recovery time. Conclusions: Vision and vestibular problems predict prolonged concussion recovery in children. A history of motion sickness may be an important premorbid factor. Public insurance status may represent problems with disparities in access to concussion care. Vision assessments in concussion must include smooth pursuits, saccades, near point of convergence (NPC), and accommodative amplitude (AA). A comprehensive, multidomain assessment is essential to predict prolonged recovery time and enable active intervention with specific school accommodations and targeted rehabilitation.

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Increased Level of Serum Hepcidin in Female Adolescent Athletes

imageObjective: To determine the serum hepcidin concentration and standard hematological parameters in a group of female adolescent athletes, compared with a group of nonathlete females. Design: A case–control study. Setting: A senior high school for athletes in Gothenburg, Sweden. Participants: All female athletes (70), at the school were offered to take part. Fifty-six athletes accepted. From a random sample of age-matched nonathletes, 71 students were recruited to the control group. Main Outcome Measures: Iron deficiency (ID) was determined by levels of serum iron, total iron-binding capacity, transferrin saturation (TS), and ferritin. Serum hepcidin was determined by a mass spectrometry method. All samples were taken at least 12 hours after training. Results: The main result was the finding of a significantly elevated serum hepcidin level in the athlete group, 4.7 nmol/L compared with 3.3 nmol/L (P

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Effectiveness of a Posterior Shoulder Stretching Program on University-Level Overhead Athletes: Randomized Controlled Trial

imageObjective: To determine whether a posterior shoulder stretch was effective in increasing internal rotation (IR) and horizontal adduction (HAd) range of motion (ROM) in overhead athletes identified as having reduced mobility. Design: Randomized controlled trial (parallel design). Setting: University-based sports medicine clinic. Participants: Thirty-seven university-level athletes in volleyball, swimming, and tennis, with IR ROM deficits ≥15°, were randomized into intervention or control groups. No subjects withdrew or were lost to follow-up. Intervention: The intervention group performed the "sleeper stretch" daily for 8 weeks, whereas the control group performed usual activities. Main Outcome Measures: Independent t tests determined whether IR and HAd ROM differences between groups were significant at 8 weeks and 2-way repeated-measures analysis of variance tests measured the rate of shoulder ROM change. Subject-reported shoulder pain and function were obtained at each evaluation. Results: Significant differences were found between the intervention and control groups' IR and HAd ROM at 8 weeks (P

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AMSSM Rising With Research Presentations

No abstract available

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AMSSM Case Podium Presentations

No abstract available

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Age Poor Guide for Chest Surgery Decisions for Transmasculine Youth

Decisions on chest reconstruction for transmasculine youth should be based on individual needs, not chronological age, new research suggests.
Reuters Health Information

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The MTT-formazan assay: Complementary technical approaches and in vivo validation in Drosophila larvae

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Publication date: Available online 1 February 2018
Source:Acta Histochemica
Author(s): Raquel Pascua-Maestro, Miriam Corraliza-Gomez, Sergio Diez-Hermano, Candido Perez-Segurado, María D. Ganfornina, Diego Sanchez
The MTT assay was the first widely accepted method to assess cytotoxicity and cell viability. However, there is controversy on whether this indicator is a useful tool. In this work we intend to expand the interpretability of the MTT study by its combination with widely used cellular biology techniques. We propose complementary approaches to the colorimetric assay, based on the use of measurements in three different settings: confocal microscopy, multi-well plate assay and flow cytometry. Using confocal microscopy, we confirmed that MTT uptake and reduction by cells is a time-dependent process, and that formazan accumulates in round-shaped organelles. Quantitative measurements with a multi-well fluorimeter combined with nuclear staining result in a useful method, yielding a ratio between formazan production and cell number that informs about the average cell metabolic state. We also found that flow cytometry is a suitable technique to measure MTT reduction in large cell populations. When assaying the effect of an oxidizing agent such as paraquat (PQ), this approach allows for the distinction of subpopulations of cells with different reducing power. Finally, we prove that it is feasible to monitor MTT reduction in an in vivo model, the Drosophila larvae, without affecting its survival rate. Formazan accumulates exclusively in the larval fat body, confirming its lipid solubility. The methods explored in this work expand the MTT potential as a useful tool to provide information of the physiological state of cells and organisms.



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An immunohistochemical and ultrastructural analysis of the retina in tadalafil (Cialis) treated rats

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Publication date: Available online 9 March 2018
Source:Acta Histochemica
Author(s): Nahla Reda Sarhan, Nesreen Moustafa Omar
Tadalafil (Cialis) is one of the most commonly used phosphodiesterase type5 (PDE5) inhibitors. This work aimed to analyze the histological and ultrastructural changes provoked by chronic tadalafil administration in the rat retina, correlate between such changes and PDE5 immunoexpression and to evaluate the possible reversibility of these changes. Thirty Sprague Dawley male rats were randomly distributed into 3 groups. Control group; given 1 ml distilled water daily for 6 weeks. Tadalafil group; given tadalafil in a daily dose of 2.6 mg/kg for 6 weeks. Withdrawal group; given tadalafil 2.6 mg/kg daily for 6 week followed by a withdrawal period of 4 weeks. Retinal specimens were prepared for histological, ultrastructural and immunohistochemical study using anti-PDE5 and anti-Bcl-2 antibodies. Morphometric and statistical studies were performed. Tadalafil group displayed a significant reduction in retinal thickness, diminished cell population of outer and inner nuclear layers, dilated blood capillaries and a significant decline in the number of ganglion cells. Significant reductions of both PDE5 and Bcl-2 immunoexpression were observed. At the ultrastructural level, the photoreceptors showed spacing of outer segments and disorganized membranous discs. Retinal neurons showed ultrastructural degenerative changes in the form of shrunken irregular nuclei, dilated rER, and disrupted mitochondria. Withdrawal group revealed preservation of histological structure and partial restoration of retinal thickness, retinal cells ultrastructure, and PDE5 and Bcl-2 immunoexpressions. In conclusion, chronic use of tadalafil could induce reversible apoptotic and degenerative changes in retinal neurons due to its inhibitory effect on PDE5 expression which affects the metabolism and viability of retinal cells.



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A novel surgical technique for a rat subcutaneous implantation of a tissue engineered scaffold

Publication date: Available online 5 March 2018
Source:Acta Histochemica
Author(s): Reza Khorramirouz, Jason L. Go, Christopher Noble, Soumen Jana, Eva Maxson, Amir Lerman, Melissa D. Young
ObjectivesSubcutaneous implantations in small animal models are currently required for preclinical studies of acellular tissue to evaluate biocompatibility, including host recellularization and immunogenic reactivity.MethodsThree rat subcutaneous implantation methods were evaluated in six Sprague Dawley rats. An acellular xenograft made from porcine pericardium was used as the tissue-scaffold. Three implantation methods were performed; 1) Suture method is where a tissue-scaffold was implanted by suturing its border to the external oblique muscle, 2) Control method is where a tissue-scaffold was implanted without any suturing or support, 3) Frame method is where a tissue-scaffold was attached to a circular frame composed of polycaprolactone (PCL) biomaterial and placed subcutaneously. After 1 and 4 weeks, tissue-scaffolds were explanted and evaluated by hematoxylin and eosin (H&E), Masson's trichrome,Picrosirius Red, transmission electron microscopy (TEM), immunohistochemistry, and mechanical testing.ResultsMacroscopically, tissue-scaffold degradation with the suture method and tissue-scaffold folding with the control method were observed after 4 weeks. In comparison, the frame method demonstrated intact tissue scaffolds after 4 weeks. H&E staining showed progressive cell repopulation over the course of the experiment in all groups with acute and chronic inflammation observed in suture and control methods throughout the duration of the study. Immunohistochemistry quantification of CD3, CD 31, CD 34, CD 163, and αSMA showed a statistically significant differences between the suture, control and frame methods (P < 0.05) at both time points. The average tensile strength was 4.03 ± 0.49, 7.45 ± 0.49 and 5.72 ± 1.34 (MPa) after 1 week and 0.55 ± 0.26, 0.12 ± 0.03 and 0.41 ± 0.32 (MPa) after 4 weeks in the suture, control, and frame methods; respectively. TEM analysis showed an increase in inflammatory cells in both suture and control methods following implantation.ConclusionRat subcutaneous implantation with the frame method was performed with success and ease. The surgical approach used for the frame technique was found to be the best methodology for in vivo evaluation of tissue engineered acellular scaffolds, where the frame method did not compromise mechanical strength, but it reduced inflammation significantly.



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Synergistic anti-proliferative effects of mTOR and MEK inhibitors in high-grade chondrosarcoma cell line OUMS-27

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Publication date: February 2018
Source:Acta Histochemica, Volume 120, Issue 2
Author(s): Singo Fukumoto, Kiyoto Kanbara, Masashi Neo
Chondrosarcoma is a malignant bone tumor that produces cartilaginous neoplastic tissue. Owing to the absence of an effective adjuvant therapy, high-grade chondrosarcoma has a poor prognosis. Therefore, it is important to develop an effective adjuvant therapy to prevent the recurrence and metastasis. Mammalian target of rapamycin (mTOR), a central regulator of cell growth, metabolism, proliferation, and survival, is considered an important target for anticancer drug development. The mitogen activated protein kinase (MAPK) pathway is another highly implicated cellular pathway in cancer and is thought to have compensatory effects in response to the inhibition of the phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR signaling pathway. We investigated the mechanism of anti-proliferative effect of the mTOR inhibitor rapamycin and MAPK/ERK (MEK) inhibitor PD 0325901, and the combined effect of rapamycin and PD 0325901 on human chondrosarcoma cell line (OUMS-27). Combination therapy with rapamycin and PD 0325901 showed a stronger anti-proliferative effect on OUMS-27 cells than rapamycin monotherapy. We confirmed that the dual inhibition of the PI3K/Akt/mTOR and RAF/MEK/ERK signaling pathways had synergistic anti-proliferative effects in OUMS-27. Our results suggest that combination therapy of mTOR and MEK inhibitor could be an effective therapeutic approach against chondrosarcoma.



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Tetrazolium salts and formazan products in Cell Biology: Viability assessment, fluorescence imaging, and labeling perspectives

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Publication date: Available online 26 February 2018
Source:Acta Histochemica
Author(s): Juan C. Stockert, Richard W. Horobin, Lucas L. Colombo, Alfonso Blázquez-Castro
For many years various tetrazolium salts and their formazan products have been employed in histochemistry and for assessing cell viability. For the latter application, the most widely used are 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), and 5-cyano-2,3-di-(p-tolyl)-tetrazolium chloride (CTC) for viability assays of eukaryotic cells and bacteria, respectively. In these cases, the nicotinamide-adenine-dinucleotide (NAD(P)H) coenzyme and dehydrogenases from metabolically active cells reduce tetrazolium salts to strongly colored and lipophilic formazan products, which are then quantified by absorbance (MTT) or fluorescence (CTC). More recently, certain sulfonated tetrazolium, which give rise to water-soluble formazans, have also proved useful for cytotoxicity assays. We describe several aspects of the application of tetrazolium salts and formazans in biomedical cell biology research, mainly regarding formazan-based colorimetric assays, cellular reduction of MTT, and localization and fluorescence of the MTT formazan in lipidic cell structures. In addition, some pharmacological and labeling perspectives of these compounds are also described.



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Localization of EFA6 (exchange factor for ARF6) isoform D in steroidogenic testicular Leydig cells of adult mice

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Publication date: Available online 26 February 2018
Source:Acta Histochemica
Author(s): Surang Chomphoo, Sawetree Pakkarato, Tarinee Sawatpanich, Hiroyuki Sakagami, Hisatake Kondo, Wiphawi Hipkaeo
EFA6 (exchange factor for ARF6) activates Arf6 (ADP ribosylation factor 6) by exchanging ADP to ATP and the resulting activated form of Arf6 is involved in the membrane trafficking and actin remodeling of cells. Our previous study has shown the selective expression/localization of EFA6D in steroidogenic adrenocortical cells in situ of adult mice. In view of the previous finding, the present study was undertaken to examine its localization in mouse Leydig cells representing another steroidogenic cell species in order to further support the possible involvement of the EFA6/Arf6 cascade via membrane trafficking in the regulation of steroidogenesis and/or secretion. A distinct band for EFA6D with the same size as that of the brain was detected in the testis of adult mice. In immuno-light microscopy, immunoreactivity for EFA6D was seen throughout the cytoplasm in most Leydig cells without any distinct accumulation along the plasmalemma. Lack of immunoreactivity for EFA6D was seen in the seminiferous tubular epithelium. In immuno-electron microscopy, the immune-labeling was seen in sporadic/focal patterns on plasma membranes and some vesicles and vacuoles subjacent to the plasma membranes. More constant and rather predominant is the labeling on numerous mitochondria. No immuno-labeling was seen in lipid droplets. The present study suggests that EFA6D is somehow involved in regulation of the synthesis and/or secretion of testosterone through the membrane-traffic by activation of Arf6. In addition, EFA6D is suggested to play in mitochondria some yet unidentified roles rather independent of Arf6-activation, which remains to be elucidated.



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Evaluating the effect of three newly approved overactive bladder syndrome treating agents on parotid and submandibular salivary glands: Modulation of CXCL10 expression

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Publication date: Available online 26 February 2018
Source:Acta Histochemica
Author(s): Basma Emad Aboulhoda, Eid Nassar Ali
BackgroundDespite enormous progresses in understanding pathophysiology of the lower urinary tract, antimuscarinics remain the chief clinically well-established approach for improving symptoms of overactive bladder (OAB). Dry mouth on the other hand remains one of the most untolerated systemic side effects of these drugs that limits their uses and results in high discontinuation rate. Three novel drugs have been recently approved by US Food and Drug Administration for treatment of OAB: trospium, darifenacin, and solifenacin.AimsThis study has been conducted to provide clear head to head comparative studying of histological and ultrastructural effect of those newly emerging drugs on parotid and submandibular salivary glands and to demonstrate the differential expression of CXCL10 to make a cogent structural and molecular assessment of the relative tolerability of these drugs and the potential mechanisms of occurrence of dry mouth.MethodsFifty male Sprague Dawley rats were equally divided into five groups: Group I (control), Group II (oxybutynin-treated), Group III (trospium-treated), Group IV (darifenacin-treated) and Group V (solifenacin-treated). Histological and ultrastructural studies were performed on parotid and submandibular glands. Measurement of salivary flow, PCR analysis and immunohistochemical assessment of CXCL10 expression have been carried-out.ResultsMuscarinic receptor antagonists led to various histological, morphometric and ultrastructural changes together with diminished salivary secretion and up-regulation of CXCL10 expression with the mildest alterations observed with solifenacin.ConclusionsSolifenacin has shown the least adverse effects to salivary glands. CXCL10 is involved in degenerative changes of salivary glands induced by muscarinic antagonists.



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Immunohistochemical localization of osteoblast activating peptide in the mouse kidney

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Publication date: Available online 11 March 2018
Source:Acta Histochemica
Author(s): Ahmed E. Noreldin, Yaser Hosny Ali Elewa, Yasuhiro Kon, Katsuhiko Warita, Yoshinao Z. Hosaka
Osteoblast activating peptide (OBAP) is a newly discovered peptide detected in the rat stomach, which has a major role in osteogenesis. Recently, we revealed its localization in the parietal cells of the rat stomach. There have been no data regarding OBAP expression in the kidney, despite its role in calcium reabsorption in renal tubules. The current study aimed to inspect the expression of OBAP in the kidney of twelve 10-week-old male C3H/HeNJc1 mice using immunohistochemistry, and immunoelectron microscopic localization. The immunohistochemical investigation revealed an OBAP positive reaction mainly in the medulla, which was stronger than the cortex of the kidney and was concentrated in the distal convoluted tubules (DCT), connecting tubules (CT), and the thick limbs of the loop of Henle (HL). Moreover, we clarified that the OBAP was co-distributed with ghrelin and calbindin (markers of the DCT). Interestingly, immunoelectron microscopy demonstrated that OBAP was concentrated in the mitochondrial inner membrane of the DCT and CT. Based on these results, it was concluded that the mitochondria of the DCT, CT, and HL of the mice kidney generate OBAP. Furthermore, our results suggest that OBAP might have a role in the regulation of calcium reabsorption by the renal tubule; however, further investigations are required to clarify this potential role.



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Localization of orexin B and orexin-2 receptor in the rat epididymis

Publication date: Available online 26 February 2018
Source:Acta Histochemica
Author(s): Giovanna Liguori, Simona Tafuri, Chika Miyoshi, Masashi Yanagisawa, Caterina Squillacioti, Valeria De Pasquale, Nicola Mirabella, Alfredo Vittoria, Anna Costagliola
The peptides orexin A (OXA) and orexin B (OXB) derived from the proteolytic cleavage of a common precursor molecule, prepro-orexin, were originally described in the rat hypothalamus. Successively, they have been found in many other brain regions as well as in peripheral organs of mammals and other less evolved animals. The widespread localization of orexins accounts for the multiple activities that they exert in the body, including the regulation of energy homeostasis, feeding, metabolism, sleep and arousal, stress, addiction, and cardiovascular and endocrine functions. Both OXA and OXB peptides bind to two G-coupled receptors, orexin-1 (OX1R) and orexin-2 (OX2R) receptor, though with different binding affinity. Altered expression/activity of orexins and their receptors has been associated with a large number of human diseases. Though at present evidence highlighted a role for orexins and cognate receptors in mammalian reproduction, their central and/or local effects on gonadal functions remain poorly known. Here, we investigated the localization of OXB and OX2R in the rat epididymis. Immunohistochemical staining of sections from caput, corpus and cauda segments of the organ showed intense signals for both OXB and OX2R in the principal cells of the lining epithelium, while no staining was detected in the other cell types. Negative results were obtained from immunohistochemical analysis of hypothalamic and testicular tissues from OX2R knock-out mice (OX2R−/−) and OX1R/OX2R double knock-out (OX1R−/−; OX2R−/−) mice, thus demonstrating the specificity of the rabbit polyclonal anti-OX2R antibody used in our study. On contrary, the same antibody clearly showed the presence of OX2R in sections from hypothalamus and testis of normal mice and rats which are well known to express the receptor. Thus, our results provide the first definite evidence for the immunohistochemical localization of OXB and OX2R in the principal cells of rat epididymis.



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Immunohistochemical localization of angiotensin AT1 receptors in the rat carotid body

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Publication date: February 2018
Source:Acta Histochemica, Volume 120, Issue 2
Author(s): Dimitrinka Y. Atanasova, Angel D. Dandov, Nikolay D. Dimitrov, Nikolai E. Lazarov
The carotid body (CB) is a major peripheral arterial chemoreceptor that initiates respiratory and cardiovascular adjustments to maintain homeostasis. Recent evidence suggests that circulating or locally produced hormones like angiotensin II acting via AT1 receptors modulate its activity in a paracrine-autocrine manner. The aim of this study was to examine the immunohistochemical localization of AT1 receptor in the CB of adult rats and to compare its expression in vehicle-treated animals, and after the long-term application of its selective blocker losartan. Immunohistochemistry revealed that a subset of CB glomeruli and the vast majority of neurons in the adjacent superior cervical ganglion (SCG) were strongly AT1 receptor-immunoreactive. In the CB immunostaining was observed in the chemosensory glomus cells typically aggregated in cell clusters while the nerve fibers in-between and large capillaries around them were immunonegative. Exogenous administration of losartan for a prolonged time significantly reduces the intensity of AT1 receptor immunostaining in the CB glomus cells and SCG neurons. Our results show that AT1 receptors are largely expressed in the rat CB under physiological conditions, and their expression is down-regulated by losartan treatment.



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Elements of molecular machinery of GABAergic signaling in the vertebrate cholinergic neuromuscular junction

Publication date: Available online 26 February 2018
Source:Acta Histochemica
Author(s): Leniz F. Nurullin, Evgeny E. Nikolsky, Artem I. Malomouzh
It is generally accepted that gamma-aminobutyric acid (GABA) is a signaling molecule abundant in central synapses. In a number of studies though, it has been shown that GABA signaling functions in the peripheral nervous system as well, in particular, in the synapses of sympathetic ganglia. However, there exists no firm evidence on the presence of GABAergic signaling cascade in the intercellular junctions of the somatic nerve system.By the use of immunohistochemistry methods, in the synaptic area of cholinergic neuromuscular contact in rat diaphragm, we have detected glutamate decarboxylase, the enzyme involved in synthesis of GABA, molecules of GABA, and also GAT-2, a protein responsible for transmembrane transport of GABA. Earlier we have also shown that metabotropic GABAB receptors have overlapping localization in the same compartment. Moreover, activation of GABAB receptors affects the intensity of acetylcholine release. These data taken together, allows us to suggest that in the mammalian cholinergic neuromuscular junction, GABA is synthesized and performs certain synaptic signaling function.

Graphical abstract

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Sinusoidal hemangioma and intravascular papillary endothelial hyperplasia: Interrelated processes that share a histogenetic piecemeal angiogenic mechanism

Publication date: Available online 25 February 2018
Source:Acta Histochemica
Author(s): Lucio Díaz-Flores, Ricardo Gutiérrez, M.ª Pino García, M. González-Gómez, Francisco J. Sáez, Lucio Díaz-Flores, José Luis Carrasco, Juan F. Madrid
Sinusoidal hemangioma, characterized by interconnecting thin-walled vascular spaces, may present papillae/pseudo-papillae and zones that resemble intravascular papillary endothelial hyperplasia (IPEH). Our objectives are to explore the existence of zones in IPEH with sinusoidal hemangioma characteristics, the mechanism of papillary and septa formation in sinusoidal hemangioma and the comparison of this mechanism with that in IPEH. For these purposes, specimens of 4 cases of each entity were selected and studied by serial histologic sections and by immunochemistry and immunofluorescence procedures. The results showed a) zones with characteristics of sinusoidal hemangioma in IPEH cases, b) presence in both entities of papillae with a cover formed by a monolayer of CD34+ and CD31+ endothelial cells (ECs) and a core formed by either type I collagen and αSMA+ cells (presenting a pericyte/smooth muscle cell aspect) or thrombotic components, and c) a similar piecemeal angiogenic mechanism in papillary formation, including sprouting of intimal ECs toward the vessel wall itself or intravascular thrombi, formation of vascular loops that encircle and separate vessel wall or thrombus components, and parietal or thrombotic papillae development. The major differences between both entities were the number, arrangement and substrate of papillae: myriad, densely grouped, parietal and thrombotic papillae in IPEH, and a linear arrangement of predominant parietal papillae in sinusoidal hemangioma, originating septa (segmentation). In conclusion, sinusoidal hemangioma and IPEH are interrelated processes, which share morphologic findings and a piecemeal angiogenic mechanism, combining sprouting and intussusceptive angiogenesis, and leading to papillary formation and vessel segmentation.



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Deletion of Thioredoxin-interacting protein ameliorates high fat diet-induced non-alcoholic steatohepatitis through modulation of Toll-like receptor 2-NLRP3-inflammasome axis: Histological and immunohistochemical study

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Publication date: Available online 23 February 2018
Source:Acta Histochemica
Author(s): Islam N. Mohamed, Nahla Reda Sarhan, Mohamed Ahmed Eladl, Azza B. El-Remessy, Mohamed El-Sherbiny
Endemic prevalence of obesity is associated with alarming increases in non-alcoholic steatohepatitis (NASH) with limited available therapeutics. Toll-like receptor2 (TLR2) and Nod-like receptor protein 3 (NLRP3) Inflammasome are implicated in hepatic steatosis, inflammation and fibrosis; the histological landmark stages of NASH. TXNIP, a member of α-arrestin family activates NLRP3 in response to various danger stimuli. The aim of current work was to investigate the effect of TXNIP genetic deletion on histological manifestations of high fat diet-induced steatohepatitis and activation of TLR2-NLRP3-inflammasome axis. Wild-type mice (WT) and TXNIP knock out (TKO) littermates were randomized to normal diet (WT-ND and TKO-ND) or high fat diet (HFD, 60% fat) (WT-HFD and TKO-HFD). After 8-weeks, liver samples from all groups were evaluated by histological, immunohistochemical and western blot analysis. HFD resulted in significant induction of micro and macrovesicular hepatic steatosis, that was associated with increased inflammatory immune cell infiltration in WT-HFD compared with WT-ND and TKO-ND controls, but not in TKO-HFD group. In parallel, WT-HFD group showed significant fibrosis and α-SMA expression; a marker of pro-fibrotic stellate-cell activation, in areas surrounding the central vein and portal circulation, versus all other groups. Western blot revealed increased activation of TLR2-NLRP3 inflammasome pathway and downstream IL-1β and TNFα in WT-HFD group, but not in TKO-HFD group. IL-1β expression coincided within the same areas of steatosis, inflammatory cell infiltration, collagen deposition and α-SMA expression in WT-HFD mice, that was significantly reduced in TKO-HFD mice. In conclusion, TXNIP deletion ameliorates the HFD-induced steatosis, inflammatory and fibrotic response via modulation of TLR2-NLRP3 inflammasome axis. Targeting TXNIP-TLR2-NLRP3 pathway may provide potential therapeutic modalities for NASH treatment.



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Non-competitive antagonists of NMDA and AMPA receptors decrease seizure-induced c-fos protein expression in the cerebellum and protect against seizure symptoms in adult rats

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Publication date: Available online 22 February 2018
Source:Acta Histochemica
Author(s): Zoltán Tóth, András Mihály, Adrienne Mátyás, Beáta Krisztin-Péva
The aim of the present study was to examine the role of ionotropic glutamate receptors in the cerebellum during generalized seizures. Epileptic neuronal activation was evaluated through the immunohistochemical detection of c-fos protein in the cerebellar cortex. Generalized seizures were precipitated by the intraperitoneal injection of 4-aminopyridine. The animals were pretreated with the NMDA receptor antagonists MK-801 (2 mg/kg), amantadine (50 mg/kg), and the AMPA receptor antagonist GYKI 52466 hydrochloride (50 mg/kg). Two hours after 4-aminopyridine injection, the number of c-fos immunostained cell nuclei was counted in serial immunohistochemical sections of the cerebellar vermis. The number of c-fos immunostained cell nuclei in the granular layer decreased significantly in animals pretreated with the glutamate receptor antagonists compared to the untreated animals having convulsion. We can conclude that mossy fiber stimulation exerts its seizure-generating action mainly through the ionotropic glutamate receptors of the mossy fiber synapses. Both NMDA and AMPA receptor antagonists are effective in reducing glutamate-mediated postsynaptic effects in the cerebellar cortex.



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Subchronic exposure to acrylamide leads to pancreatic islet remodeling determined by alpha cell expansion and beta cell mass reduction in adult rats

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Publication date: Available online 15 February 2018
Source:Acta Histochemica
Author(s): Milena Stošić, Milica Matavulj, Jelena Marković
Acrylamide (AA) is a toxic substance, used to synthesize polymers for industrial and laboratory processes. Also, AA is a food contaminant formed during the high temperature preparation of carbohydrate-rich food. The main subject of this study was to examine effects of subchronic AA treatment on the islets of Langerhans of adult rats. Adult male Wistar rats were orally treated with 25 or 50 mg/kg bw of AA for 3 weeks. Qualitative and quantitative immunohistochemical evaluation of glucagon and insulin expression and stereological analyses of pancreatic alpha and beta cells were performed. Serum insulin and glucose levels were measured. Analysis of glucagon-immunostained sections revealed a dose-dependent increase of intensity of glucagon immunopositive signal, alpha cell surface and numerical densities, volume density of alpha cell nuclei and nucleocytoplasmic ratio in AA-treated groups compared to the control. In insulin-immunolabeled pancreatic sections in AA-treated animals was observed decrease of intensity of insulin immunopositive signal, beta cell surface, numerical and volume densities and volume density of beta cell cytoplasm. Serum insulin and glucose concentrations remained unchanged after both AA treatments. The number of islets of Langerhans was not affected by AA treatment. Our results suggest that AA subchronic treatment of adult rats leads to remodeling of islet of Langerhans characterized by alpha cell expansion and beta cell mass reduction.



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Expression patterns of claudin-5 and its related signals during luteal regression in pseudopregnant rats: The enhanced effect of additional PGF treatment

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Publication date: Available online 12 February 2018
Source:Acta Histochemica
Author(s): Lina Qi, Jingle Jiang, Pengjin Jin, Meiqian Kuang, Quanwei Wei, Fangxiong Shi, Dagan Mao
To study the expression patterns of claudin-5 and its related signals during luteal regression in rats, a sequential PMSG/hCG treatment paradigm was used to obtain a single, well-defined generation of corpus luteum (CL). A total of 35 rats were treated with one PGF or two PGF at an interval of 24 h from day 7 of pseudopregnancy to induce CL regression. Serum and ovaries were collected at 0, 2, 4, 8 or 24 h after one PGF injection (1 PGF), 2 or 24 h after two PGF injections (2 PGF). The serum progesterone level was detected by RIA; the ovarian expression of claudin-5, the phosphorylations of STAT3 (p-STAT3), Akt (p-Akt), ERK1/2 (p-ERK) and p38 MAPK (p-p38) were detected by western blot, real-time PCR and IHC. Results showed that serum progesterone (P4) decreased after PGF treatment. Claudin-5 mRNA decreased at 4 h and 8 h after 1 PGF and 2 h after 2 PGF, and claudin-5 protein decreased at 4 h after 1 PGF. p-STAT3 increased at 4 h after 1 PGF and 2 h after 2 PGF. p-ERK increased at 2 h after 2 PGF. The level of p-Akt decreased at 4 h after 1 PGF. PGF treatment did not alter the phosphorylation of p38 MAPK at any time points in this study. IHC results revealed that claudin-5 was expressed in the nuclei and cytoplasm of steroidogenic cells and in the vessels, while PGF induced-p-STAT3 was expressed uniformly in the cytoplasm of luteal steroidogenic cells. In conclusion, PGF treatment decreased the expression of claudin-5 and the additional PGF treatment enhanced the decrease in claudin-5 mRNA expression and the increases in ERK1/2 and STAT3 phosphorylation in the corpus luteum of pseudopregnant rats, which will contribute new information to the further study of molecular mechanism of luteal regression.



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In situ analysis of gelatinolytic activity in human dentin

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Publication date: February 2018
Source:Acta Histochemica, Volume 120, Issue 2
Author(s): Thiago Henrique Scarabello Stape, Leo Tjäderhane, Arzu Tezvergil-Mutluay, Wagner Gomes Da Silva, Alan Roger dos Santos Silva, Wander José da Silva, Marcelo Rocha Marques
Matrix metalloproteinases (MMPs) such as gelatinases are differentially expressed in human tissues. These enzymes cleave specific substrates involved in cell signaling, tissue development and remodeling and tissue breakdown. Recent evidences show that gelatinases are crucial for normal dentin development and their activity is maintained throughout the entire tooth function in the oral cavity. Due to the lack of information about the exact location and activity of gelatinases in mature human dentin, the present study was designed to examine gelatinolytic levels in sound dentin. In situ zymography using confocal microscopy was performed on both mineralized and demineralized dentin samples. Sites presenting gelatinase activity were identified throughout the entire biological tissue pursuing different gelatinolytic levels for distinct areas: predentin and dentinal tubule regions presented higher gelatinolytic activity compared to intertubular dentin. Dentin regions with higher gelatinolytic activity immunohistochemically were partially correlated with MMP-2 expression. The maintenance of gelatinolytic activity in mature dentin may have biological implications related to biomineralization of predentin and tubular/peritubular dentinal regions, as well as regulation of defensive mechanisms of the dentin-pulp complex.



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Growth factors FGF8 and FGF2 and their receptor FGFR1, transcriptional factors Msx-1 and MSX-2, and apoptotic factors p19 and RIP5 participate in the early human limb development

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Publication date: Available online 4 February 2018
Source:Acta Histochemica
Author(s): Tina Becic, Darko Kero, Katarina Vukojevic, Snjezana Mardesic, Mirna Saraga-Babic
The expression pattern of fibroblast growth factors FGF8 and FGF2 and their receptor FGFR1, transcription factors MSX-1 and MSX-2, as well as cell proliferation (Ki-67) and cell death associated caspase-3, p19 and RIP5 factors were analyzed in histological sections of eight 4th-9th-weeks developing human limbs by immunohistochemistry and semi-thin sectioning. Increasing expression of all analyzed factors (except FGF8) characterized both the multilayered human apical ectodermal ridge (AER), sub-ridge mesenchyme (progress zone) and chondrocytes in developing human limbs. While cytoplasmic co-expression of MSX-1 and MSX-2 was observed in both limb epithelium and mesenchyme, p19 displayed strong cytoplasmic expression in non-proliferating cells. Nuclear expression of Ki-67 proliferating cells, and partly of MSX-1 and MSX-2 was detected in the whole limb primordium. Strong expression of factors p19 and RIP5, both in the AER and mesenchyme of human developing limbs indicates their possible involvement in control of cell senescence and cell death. In contrast to animal studies, expression of FGFR1 in the surface ectoderm and p19 in the whole limb primordium might reflect interspecies differences in limb morphology. Expression of FGF2 and downstream RIP5 gene, and transcription factors Msx-1 and MSX-2 did not show human-specific changes in expression pattern. Based on their spatio-temporal expression during human limb development, our study indicates role of FGFs and Msx genes in stimulation of cell proliferation, limb outgrowth, digit elongation and separation, and additionally MSX-2 in control of vasculogenesis. The cascade of orchestrated gene expressions, including the analyzed developmental factors, jointly contribute to the complex human limb development.



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Expression profile of polycomb group proteins in odontogenic keratocyst and ameloblastoma

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Publication date: Available online 4 February 2018
Source:Acta Histochemica
Author(s): Puangwan Lapthanasupkul, Rachai Juengsomjit, Sopee Poomsawat, Tawepong Arayapisit
Polycomb group (PcG) proteins are repressive chromatin modifiers required for proliferation and development. PcG proteins form two large repressive complexes, namely, Polycomb Repressive Complex 1 and 2. These proteins have been shown to drive tumorigenesis by repressing cell-type specific sets of target genes. Using immunohistochemistry, we investigated the expression patterns of five human PcG proteins, including Bmi-1, Ring1b, Mel-18, Ezh2, and Suz12, in various cellular components of odontogenic keratocysts (OKCs), ameloblastomas and, pericoronal follicles (PFs). In OKCs, expression of PcG proteins were found in the majority of cases while the expression pattern was relatively different for each PcG proteins. All PcG proteins were strongly expressed in the basal cells while some proteins showed variable expression in the parabasal and luminal cell layer of OKCs. In ameloblastomas, almost all PcG proteins showed a similar expression pattern of moderate to strong staining in the peripheral ameloblast-like cells and metaplastic squamous cells. Some of the central stellate reticulum-like cells also showed positive reaction to most PcG proteins. In PFs, most PcG proteins were intensely expressed in odontogenic epithelium lining the follicles, except Mel-18 and Suz12. The present study provides the initial evidence regarding epigenetic involvement by PcG proteins in these odontogenic lesions. Although these proteins are known to be in the same repressive group proteins, differential expression patterns of these proteins in OKCs and ameloblastomas indicates that these proteins may play different roles in pathogenesis of these odontogenic lesions.



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Apelin/APJ expression in the heart and kidneys of hypertensive rats

Publication date: Available online 1 February 2018
Source:Acta Histochemica
Author(s): Rahime Sekerci, Nuray Acar, Filiz Tepekoy, Ismail Ustunel, Nigar Keles-Celik
Hypertension is an important health problem that is manifested by systemic arterial blood pressure being permanently elevated and leading to serious complications. Hypertension is the basis for coronary heart diseases, heart failure, kidney damage, cerebrovascular diseases. Due to ethical concerns, there is no detailed study of the mechanism, side effects and treatment of hypertension in humans. For this reason, specific studies related to the organ of hypertension are performed in experimental animals. The heart and kidney tissue, which are the most important organs that hypertension has damaged, have formed specific organs of our work.In our experimental study, a total of 35 (hypertensive group: 20, control group: 15) Rattus Norvegicus Wistar albino rats were used. In order to obtain our hypertension model, our experimental animals were given L-NAME together with drinking water for six weeks. After six weeks, the experimental procedures were terminated. Heart and kidney tissues of the hypertensive and control group were obtained. Expression of apelin and apelin receptor (APJ) was demonstrated by immunohistochemical and Western Blot protocols.Hypertrophic cardiac atrium of the hearts of the large cavities, interventricular septum and myocardium to the disintegration, as well as an increase in the diameter of the coronary artery has been observed. In general, kidney tissues of the hypertensive group showed narrowing in cortical renal structures and enlargement in structures in the renal medulla.As a result, in hypertensive cases, there was an increase in expression of Apelin and APJ receptor in heart tissue, and a decrease in expression of Apelin and APJ receptor in kidney tissue. We think that our findings may contribute to experimental or clinical studies related to hypertension and apelin.



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Surgery of language-eloquent tumors in patients not eligible for awake surgery: the impact of a protocol based on navigated transcranial magnetic stimulation on presurgical planning and language outcome, with evidence of tumor-induced intra-hemispheric plasticity

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Publication date: Available online 11 March 2018
Source:Clinical Neurology and Neurosurgery
Author(s): Giovanni Raffa, Maria C. Quattropani, Antonino Scibilia, Alfredo Conti, Filippo Flavio Angileri, Felice Esposito, Carmela Sindorio, Salvatore Massimiliano Cardali, Antonino Germanò, Francesco Tomasello
ObjectivesAwake surgery and intraoperative monitoring represent the gold standard for surgery of brain tumors located in the perisylvian region of the dominant hemisphere due to their ability to map and preserve the language network during surgery. Nevertheless, in some cases awake surgery is not feasible. This could increase the risk of postoperative language deficit. Navigated transcranial magnetic stimulation (nTMS) and nTMS-based DTI fiber tracking (DTI-FT) provide a preoperative mapping and reconstruction of the cortico-subcortical language network. This can be used to plan and guide the surgical strategy to preserve the language function. The objective if this study is to describe the impact of a non-invasive preoperative protocol for mapping the language network through the nTMS and nTMS-based DTI-FT in patients not eligible for awake surgery and thereby operated under general anesthesia for suspected language-eloquent brain tumors.Patients and methodsWe reviewed clinical data of patients not eligible for awake surgery and operated under general anaesthesia between 2015 and 2016. All patients underwent nTMS language cortical mapping and nTMS-based DTI-FT of subcortical language fascicles. The nTMS findings were used to plan and guide the maximal safe resection of the tumor. The impact on postoperative language outcome and the accuracy of the nTMS-based mapping in predicting language deficits were evaluated.ResultsTwenty patients were enrolled in the study. The nTMS-based reconstruction of the language network was successful in all patients. Interestingly, we observed a significant association between tumor localization and the cortical distribution of the nTMS errors (p=0.004), thereby suggesting an intra-hemispheric plasticity of language cortical areas, probably induced by the tumor itself. The nTMS mapping disclosed the true-eloquence of lesions in 12 (60%) of all suspected cases. In the remaining 8 cases (40%) the suspected eloquence of the lesion was disproved. The nTMS-based findings guided the planning and surgery through the visual feedback of navigation. This resulted in a slight reduction of the postoperative language performance at discharge that was completely recovered after one month from surgery. The accuracy of the nTMS-based protocol in predicting postoperative permanent deficits was significantly high, especially for false-eloquent lesions (p=0.04; sensitivity 100%, specificity 57.14%, negative predictive value 100%, positive predicitive value 50%).ConclusionsThe nTMS-based preoperative mapping allows for a reliable visualization of the language network, being also able to identify an intra-hemispheric tumor-induced cortical plasticity. It allows for a customized surgical strategy that could preserve post-operative language function. This approach should be considered as a support for neurosurgeons whenever approaching patients affected by suspected language-eloquent tumors but not eligible for awake surgery.



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