Publication date: July 2016
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 150, Issue 1
Author(s): Yasuyo Sugawara, Yoshihito Ishihara, Teruko Takano-Yamamoto, Takashi Yamashiro, Hiroshi Kamioka
The orofacial muscle is an important factor in the harmony of the occlusion, and its dysfunction significantly influences a patient's occlusion after craniofacial growth and development. In this case report, we describe the successful orthodontic treatment of a patient with unilateral orofacial muscle dysfunction. A boy, 10 years 0 months of age, with a chief complaint of anterior open bite, was diagnosed with a Class III malocclusion with facial musculoskeletal asymmetry. His maxillomandibular relationships were unstable, and he was unable to lift the right corner of his mouth upon smiling because of weak right orofacial muscles. A satisfactory occlusion and a balanced smile were achieved after orthodontic treatment combined with orofacial myofunctional therapy, including muscle exercises. An acceptable occlusion and facial proportion were maintained after a 2-year retention period. These results suggest that orthodontic treatment with orofacial myofunctional therapy is an effective option for a patient with orofacial muscle dysfunction.
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Παρασκευή 1 Ιουλίου 2016
Orthodontic treatment of a patient with unilateral orofacial muscle dysfunction: The efficacy of myofunctional therapy on the treatment outcome
Information for readers
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 150, Issue 1
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Authors’ response
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 150, Issue 1
Author(s): Sophie Gray, Hamza Bennani, Mauro Farella
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Relationship of maxillary 3-dimensional posterior occlusal plane to mandibular spatial position and morphology
Publication date: July 2016
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 150, Issue 1
Author(s): Jorge C. Coro, Roberto L. Velasquez, Ivette M. Coro, Timothy T. Wheeler, Susan P. McGorray, Sadao Sato
IntroductionThe purpose of this study was to examine the relationship of the 3-dimensional (3D) posterior occlusal plane (POP) and the mandibular 3D spatial position. The relationship of the POP to mandibular morphology was also investigated.MethodsRetrospective data from a convenience sample of pretreatment diagnostic cone-beam computed tomography scans were rendered using InVivo software (Anatomage, San Jose, Calif). The sample consisted of 111 subjects (51 male, 60 female) and included growing and nongrowing subjects of different races and ethnicities. The 3D maxillary POP was defined by selecting the cusp tips of the second premolars and the second molars on the rendered images of the subjects. The angles made by this plane, in reference to the Frankfort horizontal plane, were measured against variables that described the mandibular position in the coronal, sagittal, and axial views. The POP was also compared with bilateral variables that described mandibular morphology.ResultsThere were significant differences of the POP among the different skeletal malocclusions (P <0.0001). The POP showed significant correlations with mandibular position in the sagittal (P <0.0001), coronal (P <0.05), and axial (P <0.05) planes. The POP also showed a significant correlation with mandibular morphology (P <0.0001).ConclusionsThese findings suggest that there is a distinct and significant relationship between the 3D POP and the mandibular spatial position and its morphology.
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Posttreatment evaluation of maxillary canine positions in 15-year-old subjects
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 150, Issue 1
Author(s): Zhou Yu
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Table of Contents
Source:American Journal of Orthodontics and Dentofacial Orthopedics, Volume 150, Issue 1
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The safety of intranasal steroids during pregnancy: A good start
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Sequence conservation predicts T cell reactivity against ragweed allergens
Abstract
Background
Objective
Methods
Results
Conclusion and clinical relevance
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Clarifying Scar Revision Techniques and Their Proper Use—Reply
In Reply We thank Thomas and colleagues for their impassioned commentary regarding our article, and we would like to address some of the issues that have been raised regarding our study.
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Celecoxib Versus Placebo in Tonsillectomy: A Prospective, Randomized, Double-Blind Placebo-Controlled Trial
Celecoxib is a cyclooxygenase-2-specific inhibitor indicated to treat acute pain and pain secondary to osteoarthritis and rheumatoid arthritis. Surgical models of acute pain have demonstrated superior pain relief to placebo. The objective of this study was to test the safety and efficacy of celecoxib for pain relief after tonsillectomy compared to placebo.
Methods:
Adult subjects were randomized to 200 mg celecoxib versus placebo with a loading dose the night before surgery then twice daily for 10 days. Subjects were instructed to supplement the study drug with hydrocodone/acetaminophen liquid or acetaminophen for pain as needed. Subjects completed a daily diary regarding their pain, nausea, vomiting, diet, and activity.
Results:
Seventeen subjects enrolled. Intraoperative blood loss was similar between groups, and no subject had postoperative bleeding. Three patients returned to the emergency department for treatment, and 2 patients could not complete the diaries, all in the placebo group. Subjects in the placebo group required statistically significant (P < .05) higher doses of narcotic and acetaminophen to control pain. Pain and diet rating scores were slightly better in the celecoxib group compared to placebo.
Conclusions:
In this small cohort, celecoxib reduced postoperative narcotic and acetaminophen requirements compared to placebo without complications.
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Clarifying Scar Revision Techniques and Their Proper Use
To the Editor We have studied the article by Ratnarathorn and colleagues, which used computer technology and an online survey platform to request random individuals to identify the aesthetic outcomes of "virtual" 2-dimensional scars placed on the faces of white persons. We would like to comment on the study from the perspective of 3 experienced facial plastic and reconstructive surgeons.
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The onset risk of carcinoma in patients continuing tacrolimus topical treatment for oral lichen planus: a case report
Abstract
Oral lichen planus is a chronic inflammatory mucocutaneous disease. Topical use of steroids and other immuno-modulating therapies have been tried for this intractable condition. Nowadays, tacrolimus ointment is used more commonly as a choice for treatment. However, a number of discussions have taken place after tacrolimus was reported to be carcinogenic. This report describes a patient who applied tacrolimus ointment to the lower lip after being diagnosed with oral lichen planus in 2008, and whose lesion developed squamous cell carcinoma in 2010. Since the relationship between tacrolimus and cancer development has been reported in only a few cases, including this case report, the clinician must be careful selecting tacrolimus as a second-line treatment for oral lichen planus.
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Mechanical Nasal Dilators for the Management of Nasal Obstruction
In this issue of JAMA Facial Plastic Surgery, Kiyohara and colleagues present a systematic review comparing currently available over-the-counter mechanical nasal dilators. Most of these devices are designed to temporarily facilitate inspiratory breathing by reducing transnasal resistance and improving inspiratory airflow in healthy individuals and in patients with nasal congestion. In their review, the authors focus on articles that describe effects in healthy individuals to compare product efficacy and include comparative cost information as well.
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Salivary bacterial leakage into implant-abutment connections: preliminary results of an in vitro study
OBJECTIVE: The occurrence of bacterial leakage in the internal surface of implants, through implant-abutment interface (IAI), is one of the parameters for analyzing the fabrication quality of the connections. The aim of this in vitro study is to evaluate two different types of implant-abutment connections: the screwed connection (Group 1) and the cemented connection (Group 2), analyzing the permeability of the IAI to bacterial colonization, using human saliva as culture medium.
PATIENTS AND METHODS: A total of twelve implants were tested, six in each experimental group. Five healthy patients were enrolled in this study. Two milliliters of non-stimulated saliva were collected from each subject and mixed in a test tube. After 14 days of incubation of the bacteria sample in the implant fixtures, a PCR-Real Time analysis was performed. Fisher's exact test was used to compare the proportions of implant-abutment assembled structures detected with bacterial leakage. Differences in the bacterial counts of the two groups were compared using the Mann-Whitney U test. A p value < 0.05 was considered significant.
RESULTS: The results showed a decreased stability with the screwed implant-abutment connections compared to the cemented implant-abutment connections. A mean total bacterial count of 1.2E+07 (± 0.25E+07) for Group 1 and of 7.2E+04 (± 14.4E+04) for Group 2 was found, with a high level of significance, p = .0001.
CONCLUSIONS: Within the limitations of this study it can be concluded that bacterial species from human saliva may penetrate along the implant-abutment interface in both connections, however the cemented connection implants showed the lowest amount of bacterial colonization.
L'articolo Salivary bacterial leakage into implant-abutment connections: preliminary results of an in vitro study sembra essere il primo su European Review.
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Surgical Management of Myringosclerosis over an Entire Perforated Tympanic Membrane by Simple Underlay Myringoplasty
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Central hypothyroidism
Abstract
Objective
Design, Patients and Measurements
Results
Conclusions
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Asthma associated with chronic rhinosinusitis: a population-based study
Background
Methods
Results
Conclusion
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Impaired brainstem and thalamic high-frequency oscillatory EEG activity in migraine between attacks
We investigated whether interictal thalamic dysfunction in migraine without aura (MO) patients is a primary determinant or the expression of its functional disconnection from proximal or distal areas along the somatosensory pathway.
Methods
Twenty MO patients and twenty healthy volunteers (HVs) underwent an electroencephalographic (EEG) recording during electrical stimulation of the median nerve at the wrist. We used the functional source separation algorithm to extract four functionally constrained nodes (brainstem, thalamus, primary sensory radial, and primary sensory motor tangential parietal sources) along the somatosensory pathway. Two digital filters (1–400 Hz and 450–750 Hz) were applied in order to extract low- (LFO) and high- frequency (HFO) oscillatory activity from the broadband signal.
Results
Compared to HVs, patients presented significantly lower brainstem (BS) and thalamic (Th) HFO activation bilaterally. No difference between the two cortical HFO as well as in LFO peak activations between the two groups was seen. The age of onset of the headache was positively correlated with HFO power in the right brainstem and thalamus.
Conclusions
This study provides evidence for complex dysfunction of brainstem and thalamocortical networks under the control of genetic factors that might act by modulating the severity of migraine phenotype.
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Curative treatment of head and neck squamous cell carcinoma
Abstract
Introduction
For the treatment of head and neck squamous cell carcinoma (HNSCC), there are currently no official standard of care guidelines in German-speaking countries, with the exception of oral cavity cancer. In order to learn about the applied treatment modalities in the clinical routine, we conducted a web-based survey to evaluate the local standards of palliative and curative treatment of HNSCC. This article focuses on the curative treatment options and organ preservation strategies.Materials and methods
The survey consisted of a web-based questionnaire that was performed between November 2013 and July 2014. The questionnaire included ten multiple-choice questions and four open questions in the section about curative treatment.Results
Altogether, 62 of the 204 addressed centers participated in the survey. For primary chemoradiation (CRT), most centers used a platinum-based chemotherapy (52/54, 96.3 %). Induction chemotherapy (ICT) was offered in 37 of the 62 centers (60 %). In oral cavity cancer, CRT and ICT were used in 37.5 and 4.3 % of the cases, respectively. In oropharyngeal cancer, CRT and ICT were applied in 44.5 and 10.3 % of cases, respectively. For hypopharyngeal cancer, 44.8 % of the patients received CRT and 11.8 % received ICT, while for laryngeal cancer 35.9 % received CRT and 9.4 % underwent ICT.Conclusion
Our data showed that a variety of treatments are used for HNSCC within German-speaking countries. Many centers offer ICT. The majority of the hospitals uses platinum-based therapy as a conservative first-line option in their organ preservation protocols.http://ift.tt/29bux9e
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Deep molecular responses for treatment-free remission in chronic myeloid leukemia
Abstract
Several clinical trials have demonstrated that some patients with chronic myeloid leukemia in chronic phase (CML-CP) who achieve sustained deep molecular responses on tyrosine kinase inhibitor (TKI) therapy can safely suspend therapy and attempt treatment-free remission (TFR). Many TFR studies to date have enrolled imatinib-treated patients; however, the feasibility of TFR following nilotinib or dasatinib has also been demonstrated. In this review, we discuss available data from TFR trials and what these data reveal about the molecular biology of TFR. With an increasing number of ongoing TFR clinical trials, TFR may become an achievable goal for patients with CML-CP.
Treatment-free remission (TFR) is an emerging treatment goal for patients with chronic myeloid leukemia in chronic phase (CML-CP). Numerous TFR clinical trials have demonstrated that some patients with CML-CP with sustained deep molecular responses on tyrosine kinase inhibitor (TKI) therapy can safely suspend TKI therapy without a loss of response. In this review, we discuss available data from TFR trials in patients with deep molecular responses to TKI therapies, including imatinib, dasatinib, and nilotinib.
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Multiplexed methylation profiles of tumor suppressor genes and clinical outcome in oligodendroglial tumors
Abstract
Aberrant methylation has been associated with transcriptional inactivation of tumor-related genes in a wide spectrum of human neoplasms. The influence of DNA methylation in oligodendroglial tumors is not fully understood. Genomic DNA was isolated from 61 oligodendroglial tumors for analysis of methylation using methylation-specific multiplex ligation-dependent probe amplification assay (MS-MLPA). We correlated methylation status with clinicopathological findings and outcome. The genes found to be most frequently methylated in oligodendroglial tumors were RASSF1A (80.3%), CASP8 (70.5%), and CDKN2A (52.5%). Kaplan–Meier survival curve analysis demonstrated longer duration of progression-free survival in patients with 19q loss, aged less than 38 years, and with a proliferative index of less than 5%. Methylation of the ESR1 promoter is significantly associated with shorter duration of overall survival and progression-free survival, and that methylation of IGSF4 and RASSF1A is significantly associated with shorter duration of progression-free survival. However, none of the methylation status of ESR1, IGSF4, and RASSF1A was of prognostic value for survival in a multivariate Cox model. A number of novel and interesting epigenetic alterations were identified in this study. The findings highlight the importance of methylation profiles in oligodendroglial tumors and their possible involvement in tumorigenesis.
A multiplexed approach was used to investigate the methylation status of 24 genes in 61 human oligodendroglial tumors and their association with clinical outcome was analyzed. These findings highlight the importance of these potential biomarkers and their promoter regions on chromosomes and their possible involvement in tumorigenesis.
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Antitumor activity of combined endostatin and thymidine kinase gene therapy in C6 glioma models
Abstract
The combination of Endostatin (ES) and Herpes Simplex Virus thymidine kinase (HSV-TK) gene therapy is known to have antitumor activity in bladder cancer. The potential effect of ES and TK therapy in glioma has not yet been investigated. In this study, pTK-internal ribosome entry site (IRES), pIRES-ES, and pTK-IRES-ES plasmids were constructed; pIRES empty vector served as the negative control. The recombinant constructs were transfected into human umbilical vein endothelial cells (HUVECs) ECV304 and C6 rat glioma cell line. Ganciclovir (GCV) was used to induce cell death in transfected C6 cells. We found that ECV304 cells expressing either ES or TK-ES showed reduced proliferation, decreased migration capacity, and increased apoptosis, as compared to untransfected cells or controls. pTK-IRES-ES/GCV or pTK-IRES/GCV significantly suppressed cell proliferation and induced cell apoptosis in C6 cells, as compared to the control. In addition, the administration of pIRES-ES, pTK-IRES/GCV, or pTK-IRES-ES/GCV therapy improved animal activity and behavior; was associated with prolonged animal survival, and a lower microvessel density (MVD) value in tumor tissues of C6 glioma rats. In comparison to others, dual gene therapy in form of pTK-IRES-ES/GCV had a significant antitumor activity against C6 glioma. These findings indicate combined TK and ES gene therapy was associated with a superior antitumor efficacy as compared to single gene therapy in C6 glioma.
The combination of Endostatin (ES) and Herpes Simplex Virus thymidine kinase (HSV-TK) gene therapy is known to have antitumor activity in bladder cancer. The potential effect of ES and TK therapy in glioma has not yet been investigated. We found that combined TK and ES gene therapy was associated with a superior antitumor efficacy as compared to single gene therapy in C6 glioma.
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Prognostic significance of signal transducer and activator of transcription 5 and 5b expression in Epstein–Barr virus-positive patients with chronic lymphocytic leukemia
Abstract
Signal transducer and activator of transcription (STAT) proteins have been intensively studied in hematologic malignancies, and the efficacy of agents against STATs in lymphomas is already under research. We investigated the expression of total STAT5 and STAT5b in peripheral blood samples of patients with chronic lymphocytic leukemia (CLL) in correlation with the presence of Epstein–Barr Virus (EBV) and its major oncoprotein (latent membrane protein 1, LMP1). The EBV load was measured in the peripheral blood by real-time PCR for the BXLF1 gene and the levels of LMP1 by PCR and ELISA. Western blotting was performed for total STAT5 and STAT5b in protein extracts. STAT5b was only expressed in patients (not in healthy subjects) and STAT5 but particularly STAT5b expression was correlated with the presence of the virus (77.3% vs. 51.2%, P = 0.006 for STAT5b) and to the expression of LMP1 (58.3% vs. 21.6%, P = 0.011 for STAT5b). Moreover, the expression of STAT5b and the presence of EBV and LMP1 were strongly negatively correlated with the overall survival of the patients (log-rank test P = 0.011, 0.015, 0.006, respectively). Double positive (for EBV and STAT5b) patients had the lowest overall survival (log-rank test P = 0.013). This is the first report of a survival disadvantage of EBV+ patients with CLL, and the first time that STAT5b expression is correlated with survival. The correlation of STAT5 expression with the presence of the virus, along with our survival correlations defines a subgroup of patients with CLL that may benefit from anti-STAT agents.
The role of signal transducer and activator of transcription proteins has been investigated in viral lymphomagenesis. We investigated the expression of total signal transducer and activator of transcription (STAT5), and STAT5b in particular, in patients with chronic lymphocytic leukemia. STAT5b was correlated with the presence of Epstein–Barr virus. Moreover, its expression was correlated with shorter overall survival of the patients. Double positive (Epstein–Barr Virus /STAT5b) patients had the lowest overall survival, thus, defining a group of patients that could benefit from the developing anti-STAT agents.
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Redox-responsive star-shaped magnetic micelles with active-targeted and magnetic-guided functions for cancer therapy
Publication date: Available online 30 June 2016
Source:Acta Biomaterialia
Author(s): Zhaomin Tang, Lei Zhang, Yi Wang, Dan Li, Zhendong Zhong, Shaobing Zhou
Highly efficient delivery of therapeutic agents to target sites is of great importance for achieving excellent therapeutic efficacy in cancer treatment. Here, we report a redox-responsive star-shaped magnetic micelle with both active-targeted and magnetic-guided functions. The magnetic star-shaped micelles are formed by self-assembly of four-arm poly(ethylene glycol) (PEG)-poly(ε-caprolactone) (PCL) copolymers with disulfide bonds as intermediate linkers. Anticancer drug doxorubicin (DOX) and magnetic iron oxide nanoparticles (Fe3O4) are simultaneously encapsulated into the hydrophobic cores. PBA ligands are chemically conjugated to the end of the hydrophilic PEG segments, endowing the active targeting of nanocarriers. Both qualitative and quantitative analyses of the intracellular uptake of these micelles with active-targeting and dual-targeting are performed in vitro by cultured with salic acid (SA)-positive tumor cells (human liver carcinoma cell line HepG2, human cervical cancer cell line HeLa) and SA-negative tumor cells (human breast adenocarcinoma cell line MCF-7, human non-small cell lung cancer cell line A549) in the presence or absence of a permanent magnetic field. In vivo biodistribution studies with active-targeting and dual-targeting and in vivo anti-tumor effect are carried out in detail after being applied to the BALB/c mice bearing mouse H22 hepatocarcinoma cells tumor model. These in vivo results demonstrate that a great amount of dual-targeted magnetic micelles accumulate around the tumor tissues by the magnetic-guiding and in turn are taken up by the tumor cells through SA-mediated endocytosis, leading to a high therapeutic efficacy to the artificial solid tumor.Statement of SignificanceA redox-responsive star-shaped magnetic micelle with both active-targeted and magnetic-guided functions was developed. Both qualitative and quantitative analysis of the intracellular uptake with dual-targeting of these micelles were performed in vitro by salic acid (SA)-positive tumor cells. The in vivo results demonstrate that a great amount of dual-targeted magnetic micelles accumulated around the tumor tissues, leading to a high therapeutic efficacy to artificial solid tumor.
Graphical abstract
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Melatonin Protects SH-SY5Y Neuronal Cells Against Methamphetamine-Induced Endoplasmic Reticulum Stress and Apoptotic Cell Death
Abstract
Methamphetamine (METH), a psychostimulant with highly neurotoxic effects, has been known to induce neuronal apoptosis in part through an endoplasmic reticulum (ER) stress pathway. Melatonin is an endogenous antioxidant compound that exerts protective effects against several neurodegenerative conditions, including METH-induced neurotoxicity, via various mechanisms. However, the role of melatonin in ER stress is still relatively unclear. In the present study, we investigated ER stress and neuronal apoptosis following METH treatment and the role of melatonin in METH-mediated ER stress-induced cell death in the SH-SY5Y neuroblastoma cell line. We found that METH caused the overexpression of ER stress-related genes, including C/EBP homologous protein and spliced X-box binding protein 1, in dose- and time-dependent manners. Moreover, METH time-dependently activated caspase-12 and -3, leading to cellular apoptosis. Furthermore, we demonstrated that pretreatment with melatonin attenuated the overexpression of ER stress-related genes and the cleavages of caspase-12 and -3 caused by METH exposure. Flow cytometry revealed that METH-mediated neuronal apoptosis was also prevented by melatonin. These findings suggest the protective effects of melatonin against ER stress and apoptosis caused by METH and other harmful agents.
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Results of NCCTG N0275 (Alliance) – a phase II trial evaluating resection followed by adjuvant radiation therapy for patients with desmoplastic melanoma
Abstract
To examine, in a prospective fashion, the utilization and efficacy of adjuvant radiation therapy (RT) in patients with resected desmoplastic melanoma (DM). Adult patients with resected, margin-negative, and nonmetastatic DM were eligible for this single-arm prospective phase II study. Patients were to receive postoperative RT, 30 Gy in five fractions, to the operative bed with 2- to 3-cm margins (depending on the tumor location). Nodal basin RT was not allowed. The primary study endpoint was the 2-year local recurrence rate (LRR). Secondary endpoints included the incidence of regional and distant metastatic disease, progression-free survival, overall survival (OS), and treatment-related toxicity. Twenty patients with a single de novo DM lesion meeting trial eligibility criteria were enrolled and treated. The 2-year LRR was 10%, with two patients demonstrating a LR within 2 years of completion of protocol therapy. No regional or distant failures occurred. OS at 2 and 5 years was 95 and 77%, respectively. There were no grade 3 or higher acute or late adverse events that were related to the protocol therapy. Adjuvant RT after wide local excision (WLE) for DM is efficacious and well tolerated. It should be considered for DM patients after margin-negative WLE. Additional study is needed to further refine low-risk patient populations that can potentially have adjuvant RT omitted as part of the treatment plan.
This prospective trial examines the efficacy of adjuvant radiation therapy in patients with resected desmoplastic melanoma.
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Results of NCCTG N0275 (Alliance) – a phase II trial evaluating resection followed by adjuvant radiation therapy for patients with desmoplastic melanoma
Abstract
To examine, in a prospective fashion, the utilization and efficacy of adjuvant radiation therapy (RT) in patients with resected desmoplastic melanoma (DM). Adult patients with resected, margin-negative, and nonmetastatic DM were eligible for this single-arm prospective phase II study. Patients were to receive postoperative RT, 30 Gy in five fractions, to the operative bed with 2- to 3-cm margins (depending on the tumor location). Nodal basin RT was not allowed. The primary study endpoint was the 2-year local recurrence rate (LRR). Secondary endpoints included the incidence of regional and distant metastatic disease, progression-free survival, overall survival (OS), and treatment-related toxicity. Twenty patients with a single de novo DM lesion meeting trial eligibility criteria were enrolled and treated. The 2-year LRR was 10%, with two patients demonstrating a LR within 2 years of completion of protocol therapy. No regional or distant failures occurred. OS at 2 and 5 years was 95 and 77%, respectively. There were no grade 3 or higher acute or late adverse events that were related to the protocol therapy. Adjuvant RT after wide local excision (WLE) for DM is efficacious and well tolerated. It should be considered for DM patients after margin-negative WLE. Additional study is needed to further refine low-risk patient populations that can potentially have adjuvant RT omitted as part of the treatment plan.
This prospective trial examines the efficacy of adjuvant radiation therapy in patients with resected desmoplastic melanoma.
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Natural history and the dawning of a new era for familial ALS
To date, more than 20 different genes have been discovered linked to the development of amyotrophic lateral sclerosis (ALS), with C9ORF72, TARDBP, SOD1 and FUS being the most prevalent.1 Since the discovery of the SOD1 mutation in 1993—the first gene associated with the disease—models based on this genetic mutation have made a significant contribution to understanding ALS pathogenesis. So far, more than 180 SOD1 mutations have been described, further contributing to ALS heterogeneity through expression as different clinical phenotypes. However, despite these advances in genetic understanding, ALS remains a universally fatal neurodegenerative disease, typically resulting in death within 2–3 years.23 The clinical, pathological and genetic heterogeneity of ALS has made it difficult to develop therapeutic targets and neuroprotective approaches.4 Until now, the only neuroprotective treatment capable of modifying the disease course is riluzole, a glutamate release inhibitor and sodium channel modulator that...
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Redox-responsive star-shaped magnetic micelles with active-targeted and magnetic-guided functions for cancer therapy
Publication date: Available online 30 June 2016
Source:Acta Biomaterialia
Author(s): Zhaomin Tang, Lei Zhang, Yi Wang, Dan Li, Zhendong Zhong, Shaobing Zhou
Highly efficient delivery of therapeutic agents to target sites is of great importance for achieving excellent therapeutic efficacy in cancer treatment. Here, we report a redox-responsive star-shaped magnetic micelle with both active-targeted and magnetic-guided functions. The magnetic star-shaped micelles are formed by self-assembly of four-arm poly(ethylene glycol) (PEG)-poly(ε-caprolactone) (PCL) copolymers with disulfide bonds as intermediate linkers. Anticancer drug doxorubicin (DOX) and magnetic iron oxide nanoparticles (Fe3O4) are simultaneously encapsulated into the hydrophobic cores. PBA ligands are chemically conjugated to the end of the hydrophilic PEG segments, endowing the active targeting of nanocarriers. Both qualitative and quantitative analyses of the intracellular uptake of these micelles with active-targeting and dual-targeting are performed in vitro by cultured with salic acid (SA)-positive tumor cells (human liver carcinoma cell line HepG2, human cervical cancer cell line HeLa) and SA-negative tumor cells (human breast adenocarcinoma cell line MCF-7, human non-small cell lung cancer cell line A549) in the presence or absence of a permanent magnetic field. In vivo biodistribution studies with active-targeting and dual-targeting and in vivo anti-tumor effect are carried out in detail after being applied to the BALB/c mice bearing mouse H22 hepatocarcinoma cells tumor model. These in vivo results demonstrate that a great amount of dual-targeted magnetic micelles accumulate around the tumor tissues by the magnetic-guiding and in turn are taken up by the tumor cells through SA-mediated endocytosis, leading to a high therapeutic efficacy to the artificial solid tumor.Statement of SignificanceA redox-responsive star-shaped magnetic micelle with both active-targeted and magnetic-guided functions was developed. Both qualitative and quantitative analysis of the intracellular uptake with dual-targeting of these micelles were performed in vitro by salic acid (SA)-positive tumor cells. The in vivo results demonstrate that a great amount of dual-targeted magnetic micelles accumulated around the tumor tissues, leading to a high therapeutic efficacy to artificial solid tumor.
Graphical abstract
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Melatonin Protects SH-SY5Y Neuronal Cells Against Methamphetamine-Induced Endoplasmic Reticulum Stress and Apoptotic Cell Death
Abstract
Methamphetamine (METH), a psychostimulant with highly neurotoxic effects, has been known to induce neuronal apoptosis in part through an endoplasmic reticulum (ER) stress pathway. Melatonin is an endogenous antioxidant compound that exerts protective effects against several neurodegenerative conditions, including METH-induced neurotoxicity, via various mechanisms. However, the role of melatonin in ER stress is still relatively unclear. In the present study, we investigated ER stress and neuronal apoptosis following METH treatment and the role of melatonin in METH-mediated ER stress-induced cell death in the SH-SY5Y neuroblastoma cell line. We found that METH caused the overexpression of ER stress-related genes, including C/EBP homologous protein and spliced X-box binding protein 1, in dose- and time-dependent manners. Moreover, METH time-dependently activated caspase-12 and -3, leading to cellular apoptosis. Furthermore, we demonstrated that pretreatment with melatonin attenuated the overexpression of ER stress-related genes and the cleavages of caspase-12 and -3 caused by METH exposure. Flow cytometry revealed that METH-mediated neuronal apoptosis was also prevented by melatonin. These findings suggest the protective effects of melatonin against ER stress and apoptosis caused by METH and other harmful agents.
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Risk factors for level V lymph node metastases in solitary papillary thyroid carcinoma with clinically lateral lymph node metastases
Abstract
The extent of lateral neck dissection (LND) in surgical resection of papillary thyroid carcinoma (PTC) with clinically lateral LNM (LLNM) remains controversial. We aimed to explore the frequency of and risk factors for level V LNM in patients with solitary PTC and clinically LLNM. To analyze the frequency and risk factors for level V LNM, we retrospectively reviewed 220 solitary PTC patients who underwent total thyroidectomy, bilateral central neck dissection, and therapeutic LND. LLNM were present in 82.3% patients, and levels II–V LNM were present in 45.9%, 62.7%, 55.5%, and 12.3% patients, respectively. Ipsilateral level V LNM was significantly associated with tumor size >10 mm, extrathyroidal extension, ipsilateral central LNM ratio ≥50%, and contralateral central LNM (CLNM), bilateral CLNM, and simultaneous levels II–IV LNM. Contralateral CLNM was an independent risk factor for level V LNM. In patients with solitary PTC and clinically LLNM, level V LNM was relatively uncommon. Therefore, routine level V lymphadenectomy may be unnecessary in these patients unless level V LNM is suspected on preoperative examination or associated risk factors, especially contralateral CLNM, are present.
Tumor size >10 mm, extrathyroidal extension, ipsilateral central LNM ratio ≥50%, and the presence of contralateral central LNM (CLNM), bilateral CLNM, and simultaneous levels II–IV LNM were risk factors for level V LNM. And contralateral CLNM was an independent risk factor for level V LNM in solitary PTC with clinically LLNM.
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Roboterassistierte Magenresektion beim Karzinom
Zusammenfassung
Hintergrund
Die laparoskopische Gastrektomie beim Karzinom wird als anspruchsvolles Verfahren angesehen. Nachteile der Laparoskopie können mithilfe der Robotertechnik bereinigt werden, die die Ausführung aufwendiger Rekonstruktionen und feiner Dissektionen erleichtern kann. Diese hilft insbesondere bei der Durchführung der Lymphadenektomie.
Ziel der Arbeit
Es soll die von uns verwendete Technik bei der roboterassistierten Gastrektomie dargestellt und Vor- und Nachteile anhand eines aktuellen Literaturreviews diskutiert werden.
Material und Methoden
Wir beschreiben unsere Technik der roboterassistierten distalen und totalen Gastrektomie beim Karzinom. Des Weiteren beurteilen wir den gegenwärtigen Stand der Literatur zu Kurzzeitergebnissen, sofort auswertbaren onkologischen Parametern und onkologischem Langzeit-Ergebnis der roboterassistierten Gastrektomie im Vergleich zur konventionellen laparoskopischen und offenen Chirurgie.
Ergebnisse
Das Roboterverfahren scheint ebenso sicher und effektiv wie konventionelle Gastrektomieverfahren beim Magenkarzinom – jedoch geht es mit einer längeren Operationszeit, aber dafür geringerem Blutverlust als die laparoskopische Gastrektomie einher.
Schlussfolgerung
Die technischen Vorteile, die der Einsatz des Roboters mit sich bringt, könnten dazu beitragen die minimalinvasive D2-Lymphadenektomie zu standardisieren und routinemäßig anzuwenden. Obwohl Langzeitergebnisse bzgl. der Überlebenszeiten noch rar sind, sind die erzielten Ergebnisse bei den sofort auswertbaren onkologischen Parametern (Anzahl der entfernten Lymphknoten und Status am Absetzungsrand) sehr ermutigend. Es sind noch weitere Studien zur Untersuchung des langzeitonkologischen Ergebnisses erforderlich.
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New insights into renal toxicity of the B-RAF inhibitor, vemurafenib, in patients with metastatic melanoma
Abstract
Purpose
Vemurafenib (VMF) is a B-RAF inhibitor used in the treatment of B-RAF-V600-mutant metastatic melanomas. Reports of acute kidney injury (AKI) in patients treated with VMF are scarce.
Methods
To investigate the incidence and severity of AKI, we conducted a retrospective, observational, monocentric study in the Lyon Sud Hospital University, France, which included 74 patients with metastatic B-RAF-mutated melanomas treated with VMF, between June 2011 and August 2014. According to the Kidney Disease Improving Global Outcomes Guidelines, AKI is defined as an increase in serum creatinine concentration exceeding the baseline concentration by 1.5 fold. Serum creatinine was thus determined before treatment, on a monthly basis during treatment, and 3 months after treatment discontinuation. Patients were divided into two main groups: AKI-positive (AKI+) and AKI-negative (AKI−) and further subdivided into three groups according to AKI severity (stage 1, 2 or 3). To visualize the tissue damage caused by VMF, kidney biopsies were performed for two stage 1 AKI+ patients.
Results
Of the 74 patients, 30 (40.5 %) were AKI−, and of the 44 AKI+ patients (59.5 %), 29 (66 %) were diagnosed within the first three months of treatment. There were significantly more men in the AKI+ group: n = 33 (75 %) versus n = 12 (40 %) women, p = 0.004 with an odds ratio for developing AKI of 4.6 (95 % CI 1.48–14.23). Most AKI + cases were considered as stage 1 (n = 40; 91 %) and the remaining four (9 %) as stage 2 AKI. Kidney biopsies revealed interstitial fibrosis and acute focal tubular damage. However, renal failure was reversible in 80 % of patients within 3 months of VMF discontinuation.
Conclusions
We observed frequent, reversible, moderately severe AKI with some histological evidence of tubular and interstitial damage in VMF-treated patients, suggesting that renal function should be carefully monitored in male patients, especially during the first 3 months.
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Long-term survival in advanced non-squamous NSCLC patients treated with first-line bevacizumab-based therapy
Abstract
Background/Aim
First-line bevacizumab-based therapies have been shown to improve clinical outcomes in patients with non-squamous non-small-cell lung cancer (NSCLC). We aimed to descriptively analyse patients with non-squamous NSCLC who received a long-term period of maintenance bevacizumab.
Patients and methods
This retrospective study included 104 patients who had already reached a progression-free survival (PFS) of at least 9 months.
Results
Median overall survival and PFS were 30.7 and 15.1 months, respectively. The overall response rate was 83 %. Weight loss ≤5 %, ECOG PS = 0, or low number of metastatic sites seem to be predictive factors of good evolution. The incidence of bevacizumab-related adverse events appeared to be similar as the previous studies.
Conclusion
Our findings show that there is a long-term survivor group whom the administration of bevacizumab resulted in a relevant prolongation of response without new safety signals. Due to the population heterogeneity, it was not possible to identify the standardised predictive factors.
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Is the clinical use of ice still relevant?
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Aspiring to inspire – serotonin, the laryngeal chemoreflex and the sudden infant death syndrome
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Editorial Board
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The onset risk of carcinoma in patients continuing tacrolimus topical treatment for oral lichen planus: a case report
Abstract
Oral lichen planus is a chronic inflammatory mucocutaneous disease. Topical use of steroids and other immuno-modulating therapies have been tried for this intractable condition. Nowadays, tacrolimus ointment is used more commonly as a choice for treatment. However, a number of discussions have taken place after tacrolimus was reported to be carcinogenic. This report describes a patient who applied tacrolimus ointment to the lower lip after being diagnosed with oral lichen planus in 2008, and whose lesion developed squamous cell carcinoma in 2010. Since the relationship between tacrolimus and cancer development has been reported in only a few cases, including this case report, the clinician must be careful selecting tacrolimus as a second-line treatment for oral lichen planus.
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Inhibitory effect of alpha-mangostin on Candida biofilms
Abstract
The objective of this study was to determine the inhibitory effect of alpha-mangostin on Candida biofilms. Candida species including Candida albicans, Candida krusei, Candida tropicalis, and Candida glabrata were tested. Candida biofilms were formed in flat-bottomed 96-well microtiter plates. The metabolic activity of cells within biofilms was quantified using the XTT assay. The results demonstrated that alpha-mangostin showed a significant anti-biofilm effect on both developing biofilms and preformed biofilms of Candida species. It may be concluded that alpha-mangostin could be an anti-biofilm agent against Candida species. Further in vivo investigations are needed to uncover the therapeutic values of this medicinal plant.
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Redox-responsive star-shaped magnetic micelles with active-targeted and magnetic-guided functions for cancer therapy
Publication date: Available online 30 June 2016
Source:Acta Biomaterialia
Author(s): Zhaomin Tang, Lei Zhang, Yi Wang, Dan Li, Zhendong Zhong, Shaobing Zhou
Highly efficient delivery of therapeutic agents to target sites is of great importance for achieving excellent therapeutic efficacy in cancer treatment. Here, we report a redox-responsive star-shaped magnetic micelle with both active-targeted and magnetic-guided functions. The magnetic star-shaped micelles are formed by self-assembly of four-arm poly(ethylene glycol) (PEG)-poly(ε-caprolactone) (PCL) copolymers with disulfide bonds as intermediate linkers. Anticancer drug doxorubicin (DOX) and magnetic iron oxide nanoparticles (Fe3O4) are simultaneously encapsulated into the hydrophobic cores. PBA ligands are chemically conjugated to the end of the hydrophilic PEG segments, endowing the active targeting of nanocarriers. Both qualitative and quantitative analyses of the intracellular uptake of these micelles with active-targeting and dual-targeting are performed in vitro by cultured with salic acid (SA)-positive tumor cells (human liver carcinoma cell line HepG2, human cervical cancer cell line HeLa) and SA-negative tumor cells (human breast adenocarcinoma cell line MCF-7, human non-small cell lung cancer cell line A549) in the presence or absence of a permanent magnetic field. In vivo biodistribution studies with active-targeting and dual-targeting and in vivo anti-tumor effect are carried out in detail after being applied to the BALB/c mice bearing mouse H22 hepatocarcinoma cells tumor model. These in vivo results demonstrate that a great amount of dual-targeted magnetic micelles accumulate around the tumor tissues by the magnetic-guiding and in turn are taken up by the tumor cells through SA-mediated endocytosis, leading to a high therapeutic efficacy to the artificial solid tumor.Statement of SignificanceA redox-responsive star-shaped magnetic micelle with both active-targeted and magnetic-guided functions was developed. Both qualitative and quantitative analysis of the intracellular uptake with dual-targeting of these micelles were performed in vitro by salic acid (SA)-positive tumor cells. The in vivo results demonstrate that a great amount of dual-targeted magnetic micelles accumulated around the tumor tissues, leading to a high therapeutic efficacy to artificial solid tumor.
Graphical abstract
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Negative correlation between tumour size and cortisol/ACTH ratios in patients with Cushing’s disease harbouring microadenomas or macroadenomas
Abstract
Purpose
Pituitary macroadenomas (MACs) represent 10–30 % of Cushing's disease (CD) cases. The aim of this study was to report the clinical, laboratorial and imaging features and postsurgical outcomes of microadenoma (MIC) and MAC patients.
Methods
Retrospective study with 317 CD patients (median 32 years old, range 9–71 years) admitted between 1990 and 2014, 74 (23.3 %) of whom had MAC.
Results
Hirsutism, plethora facial, muscular weakness and muscular atrophy were more frequent in the MIC patients. Nephrolithiasis, osteopenia, hyperprolactinaemia and galactorrhoea were more prevalent in MAC patients. The morning serum cortisol (Fs), nocturnal salivary cortisol (NSC), nocturnal Fs (Fs 2400 h), low- and high-dose dexamethasone suppression test results and CRH and desmopressin test results were similar between the subgroups. MIC patients showed higher urinary cortisol at 24 h (UC), and MAC patients presented higher ACTH levels but lower Fs/ACTH, Fs 2400 h/ACTH, NSC/ACTH and UC/ACTH ratios. There were negative correlations of tumour size with Fs/ACTH, Fs 2400 h/ACTH, NSC/ACTH and UC/ACTH ratios. Overall, the postsurgical remission and recurrence rates were similar between MIC and MAC. However, patients in remission (MIC + MAC) showed smaller tumour diameters and a lower prevalence of invasion and extension on MRI.
Conclusions
Despite exhibiting higher plasma ACTH levels, CD patients with MAC presented lower cortisol/ACTH ratios than did patients with MIC, with a negative correlation between tumour size and cortisol/ACTH ratios. The overall postsurgical remission and recurrence rates were similar between MIC and MAC patients, with those with larger and/or invasive tumours showing a lower remission rate.
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Aedes aegypti mosquitoes transmit dengue, chikungunya, and zika viruses. A study published in PLOS NTDs reports a new technique that could make one approach to mosquito control--using Wolbachia bacteria that reduce the mosquitos' ability to transmit viral pathogens--a whole lot easier and cheape...
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Erratum to: Feasibility and usefulness of ultrasonography in idiopathic intracranial hypertension or secondary intracranial hypertension
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The onset risk of carcinoma in patients continuing tacrolimus topical treatment for oral lichen planus: a case report
Abstract
Oral lichen planus is a chronic inflammatory mucocutaneous disease. Topical use of steroids and other immuno-modulating therapies have been tried for this intractable condition. Nowadays, tacrolimus ointment is used more commonly as a choice for treatment. However, a number of discussions have taken place after tacrolimus was reported to be carcinogenic. This report describes a patient who applied tacrolimus ointment to the lower lip after being diagnosed with oral lichen planus in 2008, and whose lesion developed squamous cell carcinoma in 2010. Since the relationship between tacrolimus and cancer development has been reported in only a few cases, including this case report, the clinician must be careful selecting tacrolimus as a second-line treatment for oral lichen planus.
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Inhibitory effect of alpha-mangostin on Candida biofilms
Abstract
The objective of this study was to determine the inhibitory effect of alpha-mangostin on Candida biofilms. Candida species including Candida albicans, Candida krusei, Candida tropicalis, and Candida glabrata were tested. Candida biofilms were formed in flat-bottomed 96-well microtiter plates. The metabolic activity of cells within biofilms was quantified using the XTT assay. The results demonstrated that alpha-mangostin showed a significant anti-biofilm effect on both developing biofilms and preformed biofilms of Candida species. It may be concluded that alpha-mangostin could be an anti-biofilm agent against Candida species. Further in vivo investigations are needed to uncover the therapeutic values of this medicinal plant.
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Redox-responsive star-shaped magnetic micelles with active-targeted and magnetic-guided functions for cancer therapy
Publication date: Available online 30 June 2016
Source:Acta Biomaterialia
Author(s): Zhaomin Tang, Lei Zhang, Yi Wang, Dan Li, Zhendong Zhong, Shaobing Zhou
Highly efficient delivery of therapeutic agents to target sites is of great importance for achieving excellent therapeutic efficacy in cancer treatment. Here, we report a redox-responsive star-shaped magnetic micelle with both active-targeted and magnetic-guided functions. The magnetic star-shaped micelles are formed by self-assembly of four-arm poly(ethylene glycol) (PEG)-poly(ε-caprolactone) (PCL) copolymers with disulfide bonds as intermediate linkers. Anticancer drug doxorubicin (DOX) and magnetic iron oxide nanoparticles (Fe3O4) are simultaneously encapsulated into the hydrophobic cores. PBA ligands are chemically conjugated to the end of the hydrophilic PEG segments, endowing the active targeting of nanocarriers. Both qualitative and quantitative analyses of the intracellular uptake of these micelles with active-targeting and dual-targeting are performed in vitro by cultured with salic acid (SA)-positive tumor cells (human liver carcinoma cell line HepG2, human cervical cancer cell line HeLa) and SA-negative tumor cells (human breast adenocarcinoma cell line MCF-7, human non-small cell lung cancer cell line A549) in the presence or absence of a permanent magnetic field. In vivo biodistribution studies with active-targeting and dual-targeting and in vivo anti-tumor effect are carried out in detail after being applied to the BALB/c mice bearing mouse H22 hepatocarcinoma cells tumor model. These in vivo results demonstrate that a great amount of dual-targeted magnetic micelles accumulate around the tumor tissues by the magnetic-guiding and in turn are taken up by the tumor cells through SA-mediated endocytosis, leading to a high therapeutic efficacy to the artificial solid tumor.Statement of SignificanceA redox-responsive star-shaped magnetic micelle with both active-targeted and magnetic-guided functions was developed. Both qualitative and quantitative analysis of the intracellular uptake with dual-targeting of these micelles were performed in vitro by salic acid (SA)-positive tumor cells. The in vivo results demonstrate that a great amount of dual-targeted magnetic micelles accumulated around the tumor tissues, leading to a high therapeutic efficacy to artificial solid tumor.
Graphical abstract
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Melatonin Protects SH-SY5Y Neuronal Cells Against Methamphetamine-Induced Endoplasmic Reticulum Stress and Apoptotic Cell Death
Abstract
Methamphetamine (METH), a psychostimulant with highly neurotoxic effects, has been known to induce neuronal apoptosis in part through an endoplasmic reticulum (ER) stress pathway. Melatonin is an endogenous antioxidant compound that exerts protective effects against several neurodegenerative conditions, including METH-induced neurotoxicity, via various mechanisms. However, the role of melatonin in ER stress is still relatively unclear. In the present study, we investigated ER stress and neuronal apoptosis following METH treatment and the role of melatonin in METH-mediated ER stress-induced cell death in the SH-SY5Y neuroblastoma cell line. We found that METH caused the overexpression of ER stress-related genes, including C/EBP homologous protein and spliced X-box binding protein 1, in dose- and time-dependent manners. Moreover, METH time-dependently activated caspase-12 and -3, leading to cellular apoptosis. Furthermore, we demonstrated that pretreatment with melatonin attenuated the overexpression of ER stress-related genes and the cleavages of caspase-12 and -3 caused by METH exposure. Flow cytometry revealed that METH-mediated neuronal apoptosis was also prevented by melatonin. These findings suggest the protective effects of melatonin against ER stress and apoptosis caused by METH and other harmful agents.
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Bill to provide $1.1 billion Zika funding dies in Senate vote
WASHINGTON — The Senate on Tuesday blocked a $1.1 billion bill to combat the Zika virus, giving Congress just two weeks to try to reach a new deal before lawmakers leave for a seven-week recess in the midst of mosquito season and a growing public health crisis.
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Automated multiple trajectory planning algorithm for the placement of stereo-electroencephalography (SEEG) electrodes in epilepsy treatment
Abstract
Purpose
About one-third of individuals with focal epilepsy continue to have seizures despite optimal medical management. These patients are potentially curable with neurosurgery if the epileptogenic zone (EZ) can be identified and resected. Stereo-electroencephalography (SEEG) to record epileptic activity with intracranial depth electrodes may be required to identify the EZ. Each SEEG electrode trajectory, the path between the entry on the skull and the cerebral target, must be planned carefully to avoid trauma to blood vessels and conflicts between electrodes. In current clinical practice trajectories are determined manually, typically taking 2–3 h per patient (15 min per electrode). Manual planning (MP) aims to achieve an implantation plan with good coverage of the putative EZ, an optimal spatial resolution, and 3D distribution of electrodes. Computer-assisted planning tools can reduce planning time by quantifying trajectory suitability.
Methods
We present an automated multiple trajectory planning (MTP) algorithm to compute implantation plans. MTP uses dynamic programming to determine a set of plans. From this set a depth-first search algorithm finds a suitable plan. We compared our MTP algorithm to (a) MP and (b) an automated single trajectory planning (STP) algorithm on 18 patient plans containing 165 electrodes.
Results
MTP changed all 165 trajectories compared to MP. Changes resulted in lower risk (122), increased grey matter sampling (99), shorter length (92), and surgically preferred entry angles (113). MTP changed 42 % (69/165) trajectories compared to STP. Every plan had between 1 to 8 (median 3.5) trajectories changed to resolve electrode conflicts, resulting in surgically preferred plans.
Conclusion
MTP is computationally efficient, determining implantation plans containing 7–12 electrodes within 1 min, compared to 2–3 h for MP.
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Ensemble average propagator-based detection of microstructural alterations after stroke
Abstract
Purpose
New analytical reconstruction techniques of diffusion weighted signal have been proposed. A previous work evidenced the exploitability of some indices derived from the simple harmonic oscillator-based reconstruction and estimation (3D-SHORE) model as numerical biomarkers of neural plasticity after stroke. Here, the analysis is extended to two additional indices: return to the plane/origin (RTPP/RTOP) probabilities. Moreover, several motor networks were introduced and the results were analyzed at different time scales.
Methods
Ten patients underwent three diffusion spectrum imaging (DSI) scans [1 week (tp1), 1 month (tp2) and 6 months (tp3) after stroke]. Ten matched controls underwent two DSI scans 1 month apart. 3D-SHORE was used for reconstructing the signal and the microstructural indices were derived. Tract-based analysis was performed along motor cortical, subcortical and transcallosal networks in the contralesional area.
Results
The optimal intra-class correlation coefficient (ICC) was obtained in the subcortical loop for propagator anisotropy (ICC \(=\) 0.96), followed by generalized fractional anisotropy (ICC \(=\) 0.94). The new indices reached the highest stability in the transcallosal network and performed well in the cortical and subcortical networks with the exception of RTOP in the cortical loop (ICC \(=\) 0.59). They allowed discriminating patients from controls at the majority of the timescales. Finally, the regression model using indices calculated along the subcortical loop at tp1 resulted in the best prediction of clinical outcome.
Conclusions
The whole set of microstructural indices provide measurements featuring high precision. The new indices allow discriminating patients from controls in all networks, except for RTPP in the cortical loop. Moreover, the 3D-SHORE indices in subcortical connections constitute a good regression model for predicting the clinical outcome at 6 months, supporting their suitability as numerical biomarkers for neuronal plasticity after stroke.
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