A 65-year-old man without a significant medical history presented to the emergency department with abdominal pain and diarrhea. He did not use any relevant medication. At physical examination, he was somnolent and hemodynamically unstable with a high fever. His peripheral circulation was poor with significant marbling of both legs, his abdomen was diffusely painful on palpation, his left leg had a necrotizing wound without an additional abscess or cellulitis (Figure 1), and he had scratches on both hands. The rest of his physical examination findings were unremarkable.
https://ift.tt/2p5ToTH
Πέμπτη 13 Σεπτεμβρίου 2018
Erratum
An error appeared in the initial publication of this article [Ram R, Halavy Y. Amit O. Extended versus Bolus Infusion of Broad Spectrum β-Lactams for Febrile Neutropenia: an Unblinded Randomized Trial. Clin Infect Dis https://doi.org/10.1093/cid/ciy258]. This article was originally published with the following error: In Table 3, under Per-Protocol population section, the first column should be labeled "Intermittent Bolus (n = 48)" and the second column should be labeled "Extended Infusion (n = 43)".
https://ift.tt/2CWfcuI
https://ift.tt/2CWfcuI
Ultrasound-guided steroid injection for the treatment of de Quervain’s disease: an anatomy-based approach
Abstract
Objective
To suggest different ultrasound-guided steroid injection (USI) techniques based on anatomical variations of the first extensor compartment (FEC), and to evaluate the usefulness of it, in patients with de Quervain's disease.
Materials and methods
Twenty-eight patients who underwent USI for de Quervain's disease were included. Anatomical variations were classified into complete sub-compartmentalization (n = 11), distal incomplete sub-compartmentalization (n = 5), and no sub-compartmentalization (n = 12) on ultrasound. Involved sub-compartments were recorded in patients with complete sub-compartmentalization. USIs were performed based on the anatomical variations: in both sub-compartments (n = 2) or only in the affected sub-compartment (n = 9) depending on the location of tenosynovitis involvement, in patients with complete sub-compartmentalization; in proximal FEC in patients with distal incomplete sub-compartmentalization (n = 5); in the common compartment in patients with no sub-compartmentalization (n = 12). Medical charts were retrospectively reviewed for evaluation of clinical outcome at follow-up visits.
Results
Twenty-three out of 28 patients were followed up with a mean period of 31.2 days after injection (6~87 days). Mean VAS was 7.96 before injection (range: 4 to 10), which was significantly reduced to 0.65 at rest and 1.57 during activity at follow-up visits (p < 0.05). Twenty-two out of 23 patients were satisfied with the results. The mean proportion of subjective pain reduction was 82.0% (median 95%).
Conclusion
Ultrasound-guided steroid injections using different injection techniques based on the anatomical variations of the FEC have shown to be beneficial in the management of de Quervain's disease.
https://ift.tt/2x83WWU
Metachronous multicentric giant cell tumour of bone
Abstract
Metachronous multicentric giant cell tumour (GCT) of bone is rare. We report a case of a 21-year-old man with metachronous multicentric GCTs, with five (including one recurrence) documented lesions reported over a span of 9 years involving various sites, which included the fifth metacarpal bone of the right hand, the intermediate cuneiform bone of the right foot, the left proximal humerus and the lateral malleolus of the right tibia. The radiological appearance of these lesions in these various sites with correlation among clinical history, histopathology and the treatment approach is described in this report. He is undergoing regular follow-up and has now once again presented with recurrence of the right tibial lesion. The case is reported for its rarity.
https://ift.tt/2OjxI1n
Evaluation of articular cartilage following rotational acetabular osteotomy for hip dysplasia using T2 mapping MRI
Abstract
Background
Rotational acetabular osteotomy (RAO) is one of the surgical treatments for acetabular dysplasia, and satisfactory results have been reported. We evaluated the postoperative changes of articular cartilage and whether the pre-operative condition of the articular cartilage influences the clinical results using T2 mapping MRI.
Methods
We reviewed 31 hips with early stage osteoarthritis in 31 patients (mean age, 39.6 years), including three men and 28 women who underwent RAO for hip dysplasia. Clinical evaluations including Japanese Orthopedic Association (JOA) score and Japanese Orthopedic Association Hip Disease Evaluation Questionnaire (JHEQ), and radiographical evaluations on X-ray were performed. Longitudinal qualitative assessment of articular cartilage was also performed using 3.0-T MRI with T2 mapping technique preoperatively, 6 months, and at 1 and 2 years postoperatively.
Results
There was no case with progression of osteoarthritis. The mean JOA score improved from 70.1 to 93.4 points, the mean postoperative JHEQ score was 68.8 points, and radiographical data also improved postoperatively. We found that the T2 values of the cartilage at both femoral head and acetabulum increased at 6 months on coronal and sagittal views. However, they significantly decreased 1 and 2 years postoperatively. The T2 values of the center to anterolateral region of acetabulum negatively correlated with postoperative JHEQ score, particularly in pain score.
Conclusions
This study suggests that biomechanical and anatomical changes could apparently cause decreased T2 values 1–2 years postoperatively compared with those preoperatively. Furthermore, preoperative T2 values of the acetabulum can be prognostic factors for the clinical results of RAO.
https://ift.tt/2xbP1uZ
Narrowing of ischiofemoral and quadratus femoris spaces in pediatric ischiofemoral impingement
Abstract
Objective
To correlate MRI findings of quadratus femoris muscle edema (QFME) with narrowing of the ischiofemoral space (IFS) and quadratus femoris space (QFS) in children, and to identify threshold values reflecting an anatomic architecture that may predispose to ischiofemoral impingement.
Materials and methods
A case-control retrospective MRI review of 49 hips in 27 children (mean, 13 years) with QFME was compared to 49 hips in 27 gender and age-matched controls. Two radiologists independently measured IFS and QFS. Generalized linear mixed-effects models were fit to compare IFS and QFS values between cases and controls, and adjust for correlation in repeated measures from the same subject. Receiver operating characteristic (ROC) analysis determined optimal threshold values.
Results
Compared to controls, cases had significantly smaller IFS (p < 0.001, both readers) and QFS (reader 1: p < 0.001; reader 2: p = 0.003). When stratified as preteen (< 13) or teenage (≥ 13), lower mean IFS and QFS were observed in cases versus controls in both age groups. Area under ROC curve for IFS and QFS was high in preteens (0.77 and 0.71) and teens (0.94 and 0.88). Threshold values were 14.9 mm (preteens) and 19 mm (teens) for IFS and 11.2 mm (preteens) and 11.1 mm (teens) for QFS. IFS and QFS were modestly correlated with age among controls only.
Conclusions
Pediatric patients with QFME had significantly narrower QFS and IFS compared with controls. IFS and QFS were found to normally increase in size with age. Optimal cutoff threshold values were identified for QFS and IFS in preteens and teenagers.
https://ift.tt/2OkEkwD
Acute posterior cruciate ligament injuries: effect of location, severity, and associated injuries on surgical management
Abstract
Objective
To correlate MRI findings of patients with posterior cruciate ligament (PCL) injury and surgical management.
Materials and methods
A retrospective search yielded 79 acute PCL injuries (36 ± 16 years old, 21 F, 58 M). Two independent readers graded PCL tear location (proximal, middle, or distal third) and severity (low-grade or high-grade partial/complete) and evaluated injury of other knee structures. When available, operative reports were examined and the performed surgical procedure was compared with injury grade, location, and presence of associated injuries.
Results
The most commonly injured knee structures in acute PCL tears were posterolateral corner (58/79, 73%) and anterior cruciate ligament (ACL) (48/79, 61%). Of the 64 patients with treatment information, 31/64 (48%) were managed surgically: 12/31 (39%) had PCL reconstruction, 13/31 (42%) had ACL reconstruction, 10/31 (32%) had posterolateral corner reconstruction, 9/31 (29%) had LCL reconstruction, 8/31 (26%) had meniscectomy, and 8/31 (26%) had fixation of a fracture. Proximal third PCL tear and multiligamentous injury were more commonly associated with surgical management (P < 0.05). Posterolateral and posteromedial corner, ACL, collateral ligament, meniscus, patellar retinaculum, and gastrocnemius muscle injury, and fracture were more likely to result in surgical management (P < 0.05). Patients with high-grade partial/complete PCL tear were more likely to have PCL reconstruction as a portion of surgical management (P < 0.05).
Conclusions
Location of PCL tear and presence of other knee injuries were associated with surgical management while high-grade/complete PCL tear grade was associated with PCL reconstruction. MRI reporting of PCL tear location, severity, and of other knee structure injuries is important for guiding clinical management.
https://ift.tt/2x9xD9Y
Non-union rate of type II and III odontoid fractures in CPPD versus a control population
Abstract
Objective
The objective was to determine if there is a significant difference between rates of non-union of type II and III odontoid fractures in patients with calcium pyrophosphate dihydrate deposition (CPPD) compared with a control population.
Materials and methods
A 10-year retrospective picture archive and communications system review was performed of 31 CPPD patients and 31 control patients. Imaging studies were reviewed for radiographic or CT evidence of osseous union and complications.
Results
There was a significant difference in the rates of non-union between the two groups, with the non-union rate reaching 90.3% in the CPPD group and 32% in the control group. Comparing the degree of displacement and angulation of the two groups did not show a significant difference.
Conclusion
The results indicate that odontoid fracture non-union rates are significantly higher in CPPD patients and should be taken into consideration when diagnosing odontoid fractures and deciding on appropriate treatment.
https://ift.tt/2OpcMGw
MR arthrogram of the postoperative glenoid labrum: normal postoperative appearance versus recurrent tears
Abstract
Objective
The purpose of this study is to describe the MR arthrogram appearance of the postoperative glenoid labrum and to describe the features consistent with recurrent tear.
Materials and Methods
We identified 30 patients who had undergone glenoid labral repair, had a subsequent MR arthrogram of his or her shoulder, and went on to repeat shoulder arthroscopy. Each MR arthrogram was reviewed blindly, and the glenoid labrum was described as normal, irregular, or torn. Additional findings recorded included the presence or absence of a paralabral cyst and suture anchors in the glenoid. The operative report was also reviewed for each patient to determine the status of the labrum at arthroscopy.
Results
Following consensus review, 18/30 MRIs were felt to demonstrate recurrent glenoid labral tear, 11/30 showed an irregular labrum, and 1/30 was called normal. The radiology impression regarding the presence or absence of a recurrent glenoid labral tear agreed with the operative report in 24/30 (80%) cases, and was discrepant in six. This equals 83.3% sensitivity and 81.8% specificity of MR arthrogram in the diagnosis of recurrent labral tear in this study. A paralabral cyst was present in 3/30 (10%) cases, all three of which were torn.
Conclusions
MR arthrogram findings of signal equal to gadolinium or fluid within or underlying the glenoid labrum and markedly diminutive or absent labrum were the most useful features to diagnose recurrent tear. Some signal underlying the labrum, which is confined to the anterosuperior quadrant, may be normal. The secondary finding of a paralabral cyst was also highly sensitive for recurrent tear.
https://ift.tt/2xb4D1I
Surveillance MRI for the detection of locally recurrent Ewing sarcoma seems futile
Abstract
Purpose
To determine the frequency of locally recurrent Ewing sarcoma on surveillance MRI and the outcome of these patients.
Materials and methods
This retrospective single-center study included all patients with newly diagnosed Ewing sarcoma who underwent surveillance MRI of the primary tumor location after primary treatment between 1997 and 2016.
Results
Thirty-two patients underwent a total of 176 local surveillance MRI scans, yielding an average of 5.5 ± 4.4 MRI scans per patient. Follow-up time of surveillance MRI after completion of primary treatment ranged between 1 and 111 months. Surveillance MRI detected five (15.6%) locally recurrent Ewing sarcomas, at 2, 4, 6, 6, and 7 months after completion of primary treatment, of whom three also had simultaneous recurrent (metastatic) disease elsewhere. Two patients had recurrent metastatic disease without any signs of locally recurrent disease on surveillance MRI. All five patients with locally recurrent disease on surveillance MRI died, at 2, 4, 5, 8, and 9 months after local recurrence detection. Patients with locally recurrent disease had a significantly worse overall survival than patients without locally recurrent disease (log-rank test, P < 0.0001).
Conclusions
A limited number of patients have locally recurrent Ewing sarcoma on surveillance MRI. These patients often have simultaneous recurrent (metastatic) disease elsewhere, and their outcome is poor. Moreover, some patients present without locally recurrent disease on MRI but disease recurrence elsewhere. Therefore, surveillance MRI currently seems to have little value and should be reconsidered, also given the costs and the repeated exposure of surviving patients to gadolinium-based contrast agents.
https://ift.tt/2OfU5EW
The lucent (CT) and enhancing (MR) rim, a sign of Paget’s disease of the skull: case report
Abstract
Osteoporosis circumscripta is sometimes observed at the skull vault and corresponds to the initial stage of Paget's disease of the bone. Differentiating osteoporosis circumscripta from other reasons for osteolytic images of the vault may be difficult. We report a case of osteoporosis circumscripta of the frontal bone. A lucent rim seen on CT scan, which was enhanced on gadolinium-enhanced MRI, delineated the abnormal bone. The patient was a 50-year-old woman who had CT scans of the skull for chronic sinusitis. Pathology examination showed typical bone changes of Paget's disease. The lucent and enhancing rim sign may help in differentiating Paget's disease from other conditions.
https://ift.tt/2xaDUlT
Widespread and debilitating hemangiomas in a patient with enchondromatosis and D-2-hydroxyglutaric aciduria
Abstract
Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (MC-HGA) (OMIM 614875) is a severe chondrodysplasia combined with a urinary excretion of D-2-hydroxyglutaric acid. Here, we reported the tenth case of this disease. A 15-year-old boy had symmetric radiolulencies in the metaphyses of the long bones suggesting enchondromatosis and platyspondyly. Remarkably, he manifested widespread cavernous hemangiomas including scalp, lips, tongue, larynx, and prepuce, with the onset of 3 years of age. Hemangiomas at the larynx had caused dyspnea and those in the oral cavity led to recurrent bleeding, requiring several surgical removals. These multiple and debilitating hemangiomas have never been previously reported in patients with MC-HGA. Mutation analyses including Sanger sequencing of genes involving in enchondromatosis and the metabolic pathway of D-2-hydroxyglutarate including PTHR1, D2HGDH, HOT, and IDH1, as well as whole-exome sequencing for proband-parent trio analysis and paired blood versus hemangioma studies showed no pathogenic variants. In summary, we reported the tenth patient with MC-HGA who manifested widespread and debilitating hemangiomas in several organs, expanding the clinical spectrum of MC-HGA.
https://ift.tt/2OlJWGG
Sonographic sequential change of the anteroinferior labrum following arthroscopic Bankart repair: quantitative and qualitative assessment
Abstract
Objective
Although arthroscopic Bankart repair is widely performed, little is known concerning the healing process of the Bankart lesion. This study aimed to describe the sonographic sequential change of the anteroinferior labrum following arthroscopic Bankart repair, both quantitatively and qualitatively.
Materials and Methods
Twenty-five subjects who had undergone arthroscopic Bankart repair were investigated using a sonographic diagnostic device equipped with shear-wave elastographic technology. In addition to measuring the elasticity of the anteroinferior labrum, the B-mode echogram of the anteroinferior labrum was classified into three grades based on the relative echogenicity. Assessment was performed in the affected shoulder 1, 2, 3, 4, 5, 6, and 12 months postoperatively and in the contralateral shoulder 1 month postoperatively for the control.
Results
The mean elasticity of the anteroinferior labrum in the affected shoulder 1 and 2 months postoperatively was significantly lower than in the contralateral shoulder (p < 0.001 for both). However, no significant difference was found after 3 months postoperatively. B-mode echograms of the anteroinferior labrum in the contralateral shoulder were classified as grade 0 in all subjects (100%), whereas the percentage of grade 0s in the affected shoulder was 0, 4, 96, and 100% at 1, 2, 3, and 4 months postoperatively.
Conclusion
Both quantitative and qualitative assessment of repaired anteroinferior labrum using ultrasound became comparable with the contralateral shoulder 3–4 months postoperatively. Ultrasound is a useful decision-supporting tool to prescribe postoperative rehabilitation protocol following arthroscopic Bankart repair, although functional recovery should also be evaluated on an individual basis.
https://ift.tt/2xbJDI7
FANCC localizes with UNC5A at neurite outgrowth and promotes neuritogenesis
The Uncoordinated 5A (UNC5A) protein is part of a family of receptors that play roles in axonal pathfinding and cell migration. We previously showed that the Fanconi anemia C protein (FANCC) interacts with UNC...
https://ift.tt/2NeCy3t
Safety and Clinical Activity of Atezolizumab in Head and Neck Cancer: Results From a Phase I Trial
Abstract
Background
Head and neck cancer (HNC) has a poor prognosis at advanced stages. Given the immunosuppressive tumor microenvironment in HNC, inhibition of the programmed death-ligand 1/programmed death-1 (PD-L1/PD-1) signaling pathway represents a promising therapeutic approach. Atezolizumab (anti–PD-L1) is efficacious against many tumor types. Here we report the clinical safety and activity from the HNC cohort of the phase Ia PCD4989g clinical trial. Patients and methods
Patients with previously-treated, advanced HNC received atezolizumab intravenously every 3 weeks for 16 cycles, up to 1 year or until loss of clinical benefit. Patients were monitored for safety and tolerability, and evaluated for response at least every 6 weeks. Baseline PD-L1 expression level and human papillomavirus (HPV) status were evaluated. Results
Thirty-two patients were enrolled; 7 patients (22%) had a primary tumor in the oral cavity, 18 (56%) in the oropharynx, 1 (3%) in the hypopharynx, 2 (6%) in the larynx, and 4 (13%) in the nasopharynx. Seventeen patients (53%) had ≥2 prior lines of therapy. Twenty-one patients (66%) experienced a treatment-related adverse event (TRAE), with 3 experiencing grade 3 TRAEs and 1 experiencing a grade 4 TRAE. No grade 5 TRAEs were reported. Objective responses by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1) occurred in 22% of patients, with a median duration of response of 7.4 months (range 2.8–45.8 months). Progression-free survival was 2.6 months (range 0.5–48.4 months), and median overall survival was 6.0 months (range 0.5–51.6+ months). Responses showed no association with HPV status or PD-L1 expression level. Conclusions
In this heavily pre-treated advanced HNC cohort, atezolizumab had a tolerable safety profile and encouraging activity, with responses observed regardless of HPV status and PD-L1 expression level. These findings warrant further investigation of atezolizumab in HNC. ClinicalTrials.gov number
NCT01375842.https://ift.tt/2Ngf3Hy
9 weeks vs 1 year adjuvant trastuzumab in combination with chemotherapy: final results of the phase III randomized Short-HER study
Abstract
Background
Chemotherapy plus 1-year trastuzumab is the standard adjuvant treatment for HER2-positive breast cancer. The efficacy of less extended trastuzumab exposure is under investigation. The Short-HER study was aimed to assess the non-inferiority of 9 weeks vs 1 year of adjuvant trastuzumab combined with chemotherapy. Patients and methods
HER2-positive breast cancer patients with node-positive or, if node negative, with at least one risk factor (pT > 2cm, G3, lympho-vascular invasion, Ki-67>20%, age ≤35 years, or hormone receptor negativity) were randomly assigned to receive sequential anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or plus 9-weeks trastuzumab (arm B, short). This study was designed as a non-inferiority trial with disease-free survival (DFS) as primary end-point. A DFS Hazard Ratio (HR) <1.29 was chosen as the non-inferiority margin. Analyses according to the frequentist and Bayesian approach were planned. Secondary endpoints included 2-year failure rate and cardiac safety. Results
1254 patients from 82 centers were randomized (arm A, long: n = 627; arm B, short: n = 626). Five-year DFS is 88% in the long and 85% in the short arm. The HR was 1.13 (90%CI 0.89;1.42), with the upper limit of the CI crossing the non-inferiority margin. According to the Bayesian analysis, the probability that the short arm is non-inferior to the long one is 80%. The 5-yr OS is 95.2% in the long and 95.0% in the short arm (HR 1.07, 90%CI0.74;1.56). Cardiac events are significantly lower in the short arm (risk-ratio 0.33, 95%CI0.22;0.50, p < 0.0001). Conclusions
This study failed to show the non-inferiority of a shorter trastuzumab administration. 1-year trastuzumab remains the standard. However, a 9-week administration decreases the risk of severe cardiac toxicity and can be an option for patients with cardiac events during treatment and for those with a low risk of relapse.https://ift.tt/2Mta2pz
Comparison of Clinical Characteristics and Outcomes in Relapsed Versus De Novo Metastatic Non–Small Cell Lung Cancer
Objectives: To compare the clinical characteristics and outcomes between relapsed and de novo metastatic non–small cell lung cancer (NSCLC). Materials and Methods: We reviewed all NSCLC diagnoses between January 1999 and December 2013 in the institutional Glans-Look Lung Cancer Database, which contains demographic, clinical, pathologic, treatment, and outcome information. Patients with distant metastasis at diagnosis (American Joint Committee on Cancer [AJCC] eighth edition, stage IV), the "de novo" cohort, were compared with the "relapsed" cohort, consisting of patients diagnosed with early stage disease (stage I/II) undergoing curative intent treatment and subsequently experiencing metastatic relapse. Survival analysis, along with univariate and multivariable analysis was performed. Results: A total of 185 relapsed and 3039 de novo patients were identified. Significantly different patterns of smoking history, histology, systemic therapy use, and disease extent were observed between the relapsed and de novo cohorts. Median overall survival from time of metastasis was significantly longer in relapsed than in de novo disease (8.9 vs. 3.7 mo, P
https://ift.tt/2NMo3mS
https://ift.tt/2NMo3mS
Differential Outcomes Among Immunosuppressed Patients With Merkel Cell Carcinoma: Impact of Immunosuppression Type on Cancer-specific and Overall Survival
Objectives: Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer with higher incidence among whites, elderly, and immunosuppressed patients. Although immunosuppressed MCC patients are at higher risk of recurrence and MCC-related death, it is unknown whether immunosuppression type is associated with differential outcomes. Materials and Methods: We retrospectively evaluated 89 nonmetastatic MCC patients with a diagnosis of chronic immunosuppression. Immunosuppression was categorized as chronic lymphocytic leukemia (31% of cohort), other hematologic malignancies (18%), solid organ transplant (21%), autoimmune disease (21%), and human immunodeficiency virus acquired deficiency syndrome (8%). Progression-free survival (PFS) and MCC-specific survival (MSS) were estimated with the cumulative incidence function. Overall survival (OS) was estimated by the Kaplan-Meier method. Results: With a median follow-up of 52 months, 53 deaths occurred (42 from MCC, 7 unknown, and 4 non-MCC). Two-year PFS, MSS, and OS were 30%, 55%, and 52%, respectively. Human immunodeficiency virus/acquired deficiency syndrome and solid organ transplant patients were diagnosed with MCC at a younger age (median 55 and 59 y, respectively) and with more advanced stage disease compared with other immunosuppressed subgroups. PFS did not significantly differ among the 5 immunosuppression subgroups (P=0.30), but significant differences were observed in MSS and OS (both P=0.01). Controlling for potential confounders for OS, including age and stage, immunosuppression type was still significantly associated with risk of death (P=0.01). Conclusions: Among immunosuppressed MCC patients, recurrent MCC is the major cause of mortality. The risk of death from MCC differs among immunosuppression types, suggesting important biological differences in host-tumor immune interactions. Portions of this work were funded from the Cancer Center Support Grant (NCI 5 P30 CA015704-43). The authors declare no conflicts of interest. Reprints: Yolanda D. Tseng, MD, Department of Radiation Oncology, University of Washington, 1959 NE Pacific Street, P.O. Box 356043, Seattle, WA 98195. E-mail: ydt2@uw.edu. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
https://ift.tt/2xdeaVi
https://ift.tt/2xdeaVi
Roles of miR-200 family members in lung cancer: more than tumor suppressors
Future Oncology, Ahead of Print.
https://ift.tt/2ND1YY7
Mental health in EMS and signs to look for in partners
Our co-hosts wrap up National Suicide Prevention Week with a discussion on signs to look for in ourselves and partners
https://ift.tt/2NF1QYa
Reliability, validity, and responsiveness of three scales for measuring balance in patients with chronic stroke
Various outcome measures are used for the assessment of balance and mobility in patients with stroke. The purpose of the present study was to examine test-retest reliability, construct validity, and responsive...
https://ift.tt/2xaNdlQ
Divergent Roles for cAMP--PKA Signaling in the Regulation of Filamentous Growth in Saccharomyces cerevisiae and Saccharomyces bayanus
The cyclic AMP - Protein Kinase A (cAMP-PKA) pathway is an evolutionarily conserved eukaryotic signaling network that is essential for growth and development. In the fungi, cAMP-PKA signaling plays a critical role in regulating cellular physiology and morphological switches in response to nutrient availability. We undertook a comparative investigation of the role that cAMP-PKA signaling plays in the regulation of filamentous growth in two closely related budding yeast species, Saccharomyces cerevisiae and Saccharomyces bayanus. Using chemical and genetic perturbations of this pathway and its downstream targets we discovered divergent roles for cAMP-PKA signaling in the regulation of filamentous growth. While cAMP-PKA signaling is required for the filamentous growth response in both species, increasing or decreasing the activity of this pathway leads to drastically different phenotypic outcomes. In S. cerevisiae, cAMP-PKA inhibition ameliorates the filamentous growth response while hyper-activation of the pathway leads to increased filamentous growth; the same perturbations in S. bayanus result in the obverse. Divergence in the regulation of filamentous growth between S. cerevisiae and S. bayanus extends to downstream targets of PKA, including several kinases, transcription factors, and effector proteins. Our findings highlight the potential for significant evolutionary divergence in gene network function, even when the constituent parts of such networks are well conserved.
https://ift.tt/2NJBYdE
Empirical Comparisons of Different Statistical Models To Identify and Validate Kernel Row Number-Associated Variants from Structured Multi-parent Mapping Populations of Maize
Advances in next generation sequencing technologies and statistical approaches enable genome-wide dissection of phenotypic traits via genome-wide association studies (GWAS). Although multiple statistical approaches for conducting GWAS are available, the power and cross-validation rates of many approaches have been mostly tested using simulated data. Empirical comparisons of single variant (SV) and multi-variant (MV) GWAS approaches have not been conducted to test if a single approach or a combination of SV and MV is effective, through identification and cross-validation of trait associated loci. In this study, kernel row number (KRN) data were collected from a set of 6,230 entries derived from the Nested Association Mapping (NAM) population and related populations. Three different types of GWAS analyses were performed: 1) single-variant (SV), 2) stepwise regression (STR) and 3) a Bayesian-based multi-variant (MV) model. Using SV, STR, and BMV models, 257, 300, and 442 KRN-associated variants (KAVs) were identified in the initial GWAS analyses. Of these, 231 KAVs were subjected to genetic validation using three unrelated populations that were not included in the initial GWAS. Genetic validation results suggest that the three GWAS approaches are complementary. Interestingly, KAVs in low recombination regions were more likely to exhibit associations in independent populations than KAVs in recombinationally active regions, probably as a consequence of linkage disequilibrium. The KAVs identified in this study have the potential to enhance our understanding of the genetic basis of ear development.
https://ift.tt/2OqSBrm
A Drosophila CRISPR/Cas9 Toolkit for Conditionally Manipulating Gene Expression in the Prothoracic Gland as a Test Case for Polytene Tissues
Targeting gene function with spatial or temporal specificity is a key goal in molecular genetics. CRISPR-Cas9 has greatly facilitated this strategy, but some standard approaches are problematic. For instance, simple tissue-specific or global overexpression of Cas9 can cause significant lethality or developmental delays even in the absence of gRNAs. In particular, we found that Gal4-mediated expression of UAS-Cas9 in the Drosophila prothoracic gland (PG) was not a suitable strategy to disrupt gene expression, since Cas9 alone caused widespread lethality. The PG is widely used for studying endocrine gland function during animal development, but tools validating PG-specific RNAi phenotypes are lacking. Here, we present a collection of modular gateway-compatible CRISPR-Cas9 tools that allow precise modulation of target gene activity with temporal and spatial specificity. We also demonstrate that Cas9 fused to the progesterone ligand-binding domain can be used to activate gene expression via RU486. Using these approaches, we were able to avoid the lethality associated with simple GAL4-mediated overexpression of Cas9 in the PG. Given that the PG is a polytene tissue, we conclude that these tools work effectively in endoreplicating cells where Cas9 has to target multiple copies of the same locus. Our toolkit can be easily adapted for other tissues and can be used both for gain- and loss-of-function studies.
https://ift.tt/2NJXoHo
Phenotype‐genotype relations in facioscapulohumeral muscular dystrophy type 1
Clinical Genetics, Volume 0, Issue ja, -Not available-.
https://ift.tt/2NGlSl2
In Reply to Fakhry et al
To the Editor: We would like to thank Fakhry et al for their comments and constructive observations with regard to the validation of their nomograms of oropharyngeal cancer that we performed in our retrospective series of consecutive patients who had complete clinical data (1-3).
https://ift.tt/2QqNh93
In Regard to Bossi et al
Bossi et al undertook an independent evaluation of the NRG oropharynx squamous cell cancer nomograms (1, 2). To do so, they retrospectively extracted relevant data, some of which may be difficult to ascertain from the medical record (tobacco use, marital status, weight loss, performance status, education, and survival outcomes). Presumably, more than 184 patients with oropharynx cancer were treated at their high-volume center between 2004 and 2016. Perhaps it is not surprising that there appear to be distinct differences between the NRG clinical trial study populations and the Bossi et al clinical series.
https://ift.tt/2OoE2VC
In Regard to Jang et al
To the Editor: We read with great interest the recent article by Jang et al reporting their findings that more than half of radiation oncology residency applicants completed an elective rotation at the institution at which they later matched (1). They report that applicants completed a median of 3 rotations, including 1 at their home institution. The authors state that the data suggest that performing multiple elective rotations helped some applicants secure their residency positions. They balance the benefit of allowing students to familiarize themselves with the program against the drawback of losing time for other medical experiences.
https://ift.tt/2OjH90W
Resection Bed Only
Data guiding management of pineal parenchymal tumors of intermediate differentiation (PPTID) are limited because they are rare and difficult to interpret owing to reclassification in 2007. Adjuvant radiation therapy (RT) appears beneficial. In the largest analysis of PPTID, adjuvant RT was associated with improved overall survival, whereas chemotherapy had no impact (1). The leptomeningeal recurrence rate was 11.8%, suggesting that not all patients require craniospinal irradiation (CSI). In a series of histopathologically reviewed pineal parenchymal tumors, none recurred in patients who underwent gross total resection (2).
https://ift.tt/2QsjSLy
In Reply to Lin and Golden
To the Editor: We would like to thank Dr. Golden and colleagues for their thoughtful input regarding our recent study (1, 2). They raise an important point regarding the use of elective rotations and the opportunity costs associated with a prolonged focus on 1 specialty during medical school (3, 4).
https://ift.tt/2OknfTz
Not to Treat
Pineal tumors of intermediate differentiation are pineal parenchymal tumors that appear histologically more aggressive than World Health Organization grade I pineocytomas. The prognosis of pineal tumors of intermediate differentiation is actually similar to that of pineocytomas in the setting of gross total resection (GTR), though they do have a higher rate of both local recurrence and leptomeningeal dissemination than lower-grade tumors. Given their rarity and the retrospective nature of the reports, the literature is limited to inform clinical management.
https://ift.tt/2QtL1hk
The Higher the Grade, the Bigger the Field
Pineal parenchymal tumors of intermediate differentiation are a rare entity. Less than 1% of all primary central nervous system malignancies arise from the pineal region, and only a small subset of that population is parenchymal in origin (1). As such, there is a distinct lack of clinical data available to develop standardized treatments.
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Defining the Place of Adjuvant Chemotherapy and Radiation for High-Risk Endometrial Cancer From Recent Randomized Clinical Trials: Some Answers, More Questions
Endometrial carcinoma is the most common gynecologic malignancy. Most patients present with early stage disease, but in about 10% to 15% of all new cases of endometrial cancer, disease is found outside the uterus at diagnosis. These patients account for more than 50% of all uterine cancer–related deaths. They are treated with adjuvant chemotherapy (CT) and/or radiation therapy (RT), although we do not know the true impact of adjuvant treatment on survival (1). This issue's Oncology Scan covers 3 recently presented or published prospective trials—Gynecology Oncology Group (GOG)-258 (2), GOG-249 (3), and Postoperative Radiation Therapy in Endometrial Carcinoma (PORTEC-3) (4)—and a National Cancer Database (NCDB) (5) analysis that tried to define optimal adjuvant treatment for high- or high-intermediate-risk endometrial cancer.
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A 63-Year-Old Woman With a Pineal Mass
A 63-year-old woman (Karnofsky performance status 80) presented with a several-month history of shuffling gait, frontal headache, and urinary urgency. Magnetic resonance imaging of the brain demonstrated hydrocephalus secondary to a 2.7-cm, fairly well demarcated, enhancing mass in the pineal gland (Fig. 1). The patient underwent suboccipital craniotomy and gross total resection, with pathology demonstrating a pineal parenchymal tumor of intermediate differentiation (World Health Organization II vs III, favoring grade III) with MIB-1 index of 10% (1).
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CDC: About One in Five U.S. Adults Have Chronic Pain
THURSDAY, Sept. 13, 2018 -- About 20.4 percent of U.S. adults have chronic pain and 8.0 percent have high-impact chronic pain, according to research published in the Sept. 14 issue of the U.S. Centers for Disease Control and Prevention's Morbidity...
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No Apparent Short-Term Cancer Risk From Recalled Valsartan
THURSDAY, Sept. 13, 2018 -- Users of valsartan contaminated with N-nitrosodimethylamine (NDMA) seem not to have increased cancer risk, according to a study published online Sept. 12 in The BMJ. Anton Pottegård, Ph.D., from the University of...
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Experts Advise Against Universal DNA Sequencing of Newborns
THURSDAY, Sept. 13, 2018 -- Newborns should not undergo universal sequencing at birth, according to a report published in the July/August issue of The Hasting Center Report. Josephine Johnston, J.D., from The Hastings Center in Garrison, N.Y., and...
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Including Calorie Count on Menus Can Cut Calories Ordered
THURSDAY, Sept. 13, 2018 -- Including calorie count information on restaurant menus can result in a reduction in calories ordered, specifically in appetizers and entrees, according to a policy paper issued by the National Bureau of Economic...
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Firearm Deaths Up Globally From 1990 to 2016
THURSDAY, Sept. 13, 2018 -- Firearm deaths increased globally between 1990 and 2016, according to a study published in the Aug. 28 issue of the Journal of the American Medical Association. Mohsen Naghavi, M.D., Ph.D., from University of Washington...
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Bowel dysfunction after sigmoid resection for cancer and its impact on quality of life
BJS, EarlyView.
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Mixed and Matched Metallo‐Nanotexaphyrin for Customizable Biomedical Imaging
Advanced Healthcare Materials, EarlyView.
https://ift.tt/2Ol2p6y
Pulmonary metastasectomy: analysis of survival and prognostic factors in 243 patients
ANZ Journal of Surgery, EarlyView.
https://ift.tt/2NbZdgT
Totally‐laparoscopic versus laparoscopic‐assisted low anterior resection for rectal cancer: are outcomes different?
ANZ Journal of Surgery, EarlyView.
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Surgical treatment of otitis media with effusion in Maori children
ANZ Journal of Surgery, EarlyView.
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Improving Patient and Caregiver Outcomes in Oncology: Team‐Based, Timely, and Targeted Palliative Care
CA: A Cancer Journal for Clinicians, EarlyView.
https://ift.tt/2NdZIa6
Abstracts presented at the winter meeting of the british association of clinical anatomists on December 14, 2017 at Queens Hospital, Burton on Trent, United Kingdom
Clinical Anatomy, EarlyView.
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The effect of resistance training on the anxiety symptoms and quality of life in elderly people with Parkinson's disease: a randomized controlled trial
ABSTRACT Objective: To assess the effects of resistance training on the anxiety symptoms and quality of life in patients with Parkinson's disease. Methods: Thirty-five elderly patients were randomly divided into two groups: 17 patients in the control group and 18 in the intervention group. All patients maintained standard pharmacological treatment for Parkinson's disease, but the intervention group participated in a 24-week resistance training program. The anxiety symptoms were assessed through the Beck's Anxiety Inventory, and quality of life by the Parkinson's Disease Questionnaire–39. Results: There was a significant reduction in anxiety level and increase in quality of life after 24 weeks of resistance training. Conclusion: The results of the present study indicate that resistance training is an effective intervention in the reduction of anxiety symptoms and improves the quality of life in elderly people with Parkinson's disease.
RESUMO Objetivo: avaliar os efeitos do treinamento resistido nos sintomas de ansiedade e na qualidade de vida em pacientes com doença de Parkinson. Métodos: Trinta e cinco pacientes idosos foram divididos randomicamente em dois grupos: 17 indivíduos no grupo controle e 18 no grupo de intervenção. Todos os sujeitos mantiveram o tratamento farmacológico padrão para a doença de Parkinson, mas o grupo de intervenção participou de um programa de treinamento resistido de 24 semanas. Os sintomas de ansiedade foram avaliados através do inventário de ansiedade de Beck e a qualidade de vida pelo questionário da doença de Parkinson-39. Resultados: Houve redução significativa no nível de ansiedade e melhora da qualidade de vida após 24 semanas de treinamento resistido. Conclusão: Os resultados do presente estudo indicam que o treinamento resistido é uma intervenção efetiva na redução dos sintomas de ansiedade e melhora a qualidade de vida em idosos com doença de Parkinson.
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Spontaneous intracranial hypotension and its complications
ABSTRACT Spontaneous intracranial hypotension (SIH) is a syndrome that was unknown until the advent of magnetic resonance imaging (MRI). It is a cause of orthostatic headache, which remains underdiagnosed and, rarely, can result in several complications including dural venous sinus thrombosis, subdural hematoma and subarachnoid hemorrhage. Some of these complications are potentially life-threatening and should be recognized promptly, mainly by imaging studies. We reviewed the MRI of nine patients with SIH and describe the complications observed in three of these patients. Two of them had subdural hematoma and one had a dural venous sinus thrombosis detected by computed tomography and MRI. We concluded that MRI findings are of great importance in the diagnosis of SIH and its complications, which often influence the clinical-surgical treatment of the patient.
RESUMO Hipotensão Intracraniana Espontânea (HIE) é uma síndrome desconhecida até o advento das imagens de Ressonância Magnética (RM). É uma causa de cefaleia ortostática que permanece subdiagnosticada e raramente resulta em complicações, como trombose de seios venosos durais, hematoma subdural e hemorragia subaracnoidea. Algumas dessas complicações são potencialmente ameaçadoras à vida e devem ser prontamente reconhecidas pelos estudos de imagem. Nós revisamos as RM de 9 pacientes com HIE e descrevemos as complicações observadas em 3 casos. Dois deles tiveram hematoma subdural e um teve trombose de seio venoso dural detectados por tomografia computadorizada e RM. Concluímos que achados de RM são de grande importância no diagnóstico de HIE e suas complicações, frequentemente influenciando o tratamento clínico-cirúrgico do paciente.
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Cross-cultural adaptation to Brazilian Portuguese of the Dementia Knowledge Assessment Tool Version Two: DKAT2
ABSTRACT The Dementia Knowledge Assessment Tool Version Two (DKAT2) was developed to measure caregivers' knowledge about the trajectory of dementia and assess changes in the knowledge before and after educational programs. The DKAT2 is a 21-item tool with questions about several aspects of dementia. The possible answers for each question are "yes", "no" or "don't know". The maximum score is 21. Objective: The aim of the study was to cross-culturally adapt the DKAT2 to Brazilian Portuguese. Methods: The essential steps to cross-culturally adapt were conducted and the final version administered to 30 caregivers of older people with dementia, sampled by convenience. Results: In the sample assessed, the mean age was 55.7 (± 12.5) years, 93.3% were female, 56.7% were sons/daughters and 23.3% were spouses of the older adults with dementia. The mean time caring for the elder was 4.7 (± 3.3) years and 70% of the caregivers had some level of burden. The mean age of the older people was 82.4 (± 6.7) years, 19 (63.3%) had a diagnosis of Alzheimer's disease, 100% were dependent for instrumental activities of daily living and 70% had some degree of dependence for basic activities of daily living. The mean score for the caregivers' knowledge level was 15.0 (± 2.5) correct answers. Conclusions: The Brazilian Portuguese version was developed and the final version is suitable for use in Brazil.
RESUMO "Dementia Knowledge Assessment Tool Version Two" (DKAT2) foi desenvolvido para medir o conhecimento de cuidadores sobre a trajetória da demência e avaliar as mudanças no conhecimento antes e depois de programas educacionais. DKAT2 é uma ferramenta de 21 itens com perguntas sobre vários aspectos da demência. As respostas possíveis para cada pergunta são "sim", "não" ou "não sei". A pontuação máxima é de 21. Objetivo: Adaptar culturalmente o DKAT2 ao português brasileiro. Métodos: Foram realizadas as etapas essenciais para a adaptação cultural e a versão final foi administrada a uma amostra de conveniência de 30 cuidadores de idosos com demência. Resultados: A idade média dos cuidadores foi de 55,7 (± 12,5) anos, 93,3% eram do sexo feminino, 56,7% eram filhos e 23,3% cônjuges dos idosos com demência. O tempo médio de cuidado ao idoso foi de 4,7 (± 3,3) anos e 70,0% dos cuidadores mostraram algum nível de sobrecarga. A média de idade dos idosos com demência foi de 82,4 (± 6,7) anos, 19 (63,3%) tiveram diagnóstico de doença de Alzheimer, 100% eram dependentes nas atividades instrumentais da vida diária e 70,0% tinham algum grau de dependência nas atividades básicas de vida diária. O escore médio do nível de conhecimento dos cuidadores foi de 15,0 (± 2,5) respostas corretas. Conclusões: A versão em português do Brasil foi obtida e mostrou-se adequada para uso no Brasil.
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Motor and non-motor wearing-off and its impact in the quality of life of patients with Parkinson's disease
ABSTRACT The wearing-off phenomenon is common in patients with Parkinson's disease. Motor and non-motor symptoms can fluctuate in relation to the "on/off" periods. Objective: To assess the impact of motor and non-motor wearing-off on activities of daily living and quality of life of patients with PD. Methods: A cross-sectional study was carried out. All patients were evaluated using the Movement Disorders Society Unified Parkinson's Disease Rating Scale. Wearing-off was assessed using the Wearing-Off Questionnaire-19, and quality of life was assessed using the Parkinson's Disease Questionnaire-8. Results: A total of 271 patients were included; 73.4% had wearing-off; 46.8% had both motor and non-motor fluctuations. Patients with both motor and non-motor wearing-off had a worst quality of life compared with those with only motor fluctuations (p = 0.047). Conclusions: Motor and non-motor fluctuations have an impact on activities of daily living and quality of life. Non-motor wearing-off may have a higher impact.
RESUMO O fenômeno de encurtamento do fim de dose é comum em pacientes com doença de Parkinson. Tanto os sintomas motores quanto os não motores podem flutuar em relação aos períodos de "on/off". Objetivo: Avaliar o impacto das flutuações motoras e não-motoras nas atividades da vida diária e qualidade de vida em pacientes com doença de Parkinson. Métodos: Um estudo transversal foi realizado. Todos os sujeitos foram avaliados utilizando a escala unificada para a doença de Parkinson da Sociedade de Distúrbios do Movimento. O encurtamento do fim de dose foi avaliado através do questionário WOQ-19 e a qualidade de vida foi avaliada através do PDQ-8. Resultados: Um total de 271 pacientes foram incluídos, 73,4% tiveram deterioração de fim de dose. A maioria dos pacientes tiveram tanto flutuações motoras quanto não-motoras (46,8%). Os pacientes com ambos os tipos de flutuações motoras e não-motoras tiveram pior qualidade de vida do que pacientes apenas com flutuações motoras (p = 0.047). Conclusões: Pacientes com flutuações motoras e não-motoras tiveram impacto significativo nas atividades da vida diária e na qualidade de vida. As flutuações não-motoras parecem ter um impacto maior que as flutuações motoras sobre a qualidade de vida.
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Blepharospasm with elevated anti-acetylcholine receptor antibody titer
ABSTRACT Objective: To determine whether serum levels of anti-acetylcholine receptor antibody (anti-AChR-Abs) are related to clinical parameters of blepharospasm (BSP). Methods: Eighty-three adults with BSP, 60 outpatients with hemifacial spasm (HFS) and 58 controls were recruited. Personal history, demographic factors, response to botulinum toxin type A (BoNT-A) and other neurological conditions were recorded. Anti-AChR-Abs levels were quantified using an enzyme-linked immunosorbent assay. Results: The anti-AChR Abs levels were 0.237 ± 0.022 optical density units in the BSP group, which was significantly different from the HFS group (0.160 ± 0.064) and control group (0.126 ± 0.038). The anti-AChR Abs level was correlated with age and the duration of response to the BoNT-A injection. Conclusion: Patients with BSP had an elevated anti-AChR Abs titer, which suggests that dysimmunity plays a role in the onset of BSP. An increased anti-AChR Abs titer may be a predictor for poor response to BoNT-A in BSP.
RESUMO Objetivo: Determinar se os níveis séricos do anticorpo antirreceptor de acetilcolina (anti-AChR-Abs) estão relacionados aos parâmetros clínicos do blefaroespasmo (BSP). Métodos: Fora recrutados 83 adultos com BSP, 60 pacientes ambulatoriais com espasmo hemifacial (HFS) e 58 controles. Foi aplicado um questionário para registrar história pessoal, fatores demográficos, resposta à toxina botulínica tipo A (BoNT-A) e outras condições neurológicas. Os níveis de anti-AChR-Abs foram quantificados usando um ensaio imunoenzimático. Resultados: O nível de anti-AChR-Abs foi de 0,237 ± 0,022 unidades de densidade óptica (OD) no grupo BSP, significativamente diferente em comparação com o grupo HFS (0,160 ± 0,064) e o grupo controle (0,126 ± 0,038). O nível de anti-AChR-Abs se correlacionou com a idade e a duração da resposta à injeção de BoNT-A. Conclusão: Pacientes com BSP apresentaram títulos elevados de anti-AChR-Abs, o que sugere que a desimunidade desempenha um papel no surgimento de BSP. O aumento do título de anti-AChR-Abs pode ser um preditor de resposta insuficiente à BoNT-A em BSP.
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Tumarkin-like phenomenon as a sign of therapeutic success in benign paroxysmal positional vertigo
ABSTRACT Objective: To describe an unusual patient reaction to maneuvers used in the treatment of posterior canal benign paroxysmal positional vertigo (PC-BPPV) that we termed the "Tumarkin-like phenomenon". Methods: At a private practice, 221 outpatients were diagnosed and treated for PC-BPPV. The treatment consisted of performing the Epley or Semont maneuvers. At the end of these maneuvers, when assuming the sitting position, the patients' reactions were recorded. Results: Thirty-three patients showed a Tumarkin-like phenomenon described by a self-reported sensation of suddenly being thrown to the ground. In the follow-up, this group of patients remained without PC-BPPV symptoms up to at least 72 hours after the maneuvers. Conclusion: The occurrence of a Tumarkin-like phenomenon at the end of Epley and Semont maneuvers for PC-BPPV may be linked with treatment success.
RESUMO Objetivo: Descrever uma reação incomum dos pacientes às manobras utilizadas no tratamento da vertigem posicional paroxística benigna do canal posterior (VPPB-CP), a qual denominamos de fenômeno Tumarkin-like. Métodos: Em uma clínica privada, 221 pacientes ambulatoriais foram diagnosticados e tratados para VPPB-CP. O tratamento consistiu em realizar as manobras de Epley ou de Semont. Ao término da manobra, ao serem colocados na posição sentado, as reações dos pacientes foram filmadas. Resultados: Trinta e três pacientes apresentaram o fenômeno de Tumarkin-like, descrito como uma sensação súbita de ser jogado no chão. O acompanhamento mostrou que todos eles permaneceram sem sintomas de VPPB até pelo menos 72 horas após as manobras. Conclusão: A ocorrência do fenômeno Tumarkin-like no final das manobras de Epley e Semont para VPPB-CP pode estar associado ao sucesso terapêutico.
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Brazilian Consensus for the Treatment of Multiple Sclerosis: Brazilian Academy of Neurology and Brazilian Committee on Treatment and Research in Multiple Sclerosis
ABSTRACT The expanding therapeutic arsenal in multiple sclerosis (MS) has allowed for more effective and personalized treatment, but the choice and management of disease-modifying therapies (DMTs) is becoming increasingly complex. In this context, experts from the Brazilian Committee on Treatment and Research in Multiple Sclerosis and the Neuroimmunology Scientific Department of the Brazilian Academy of Neurology have convened to establish this Brazilian Consensus for the Treatment of MS, based on their understanding that neurologists should be able to prescribe MS DMTs according to what is better for each patient, based on up-to-date evidence and practice. We herein propose practical recommendations for the treatment of MS, with the main focus on the choice and management of DMTs, as well as present a review of the scientific rationale supporting therapeutic strategies in MS.
RESUMO O crescent arsenal terapêutico na esclerose múltipla (EM) tem permitido tratamentos mais efetivos e personalizados, mas a escolha e o manejo das terapias modificadoras da doença (TMDs) tem se tornado cada vez mais complexos. Neste contexto, especialistas do Comitê Brasileiro de Tratamento e Pesquisa em Esclerose Múltipla e do Departamento Científico de Neuroimunologia da Academia Brasileira de Neurologia reuniram-se para estabelecer este Consenso Brasileiro para o Tratamento da EM, baseados no entendimento de que neurologistas devem ter a possibilidade de prescrever TMDs para EM de acordo com o que é melhor para cada paciente, com base em evidências e práticas atualizadas. Por meio deste documento, propomos recomendações práticas para o tratamento da EM, com foco principal na escolha e no manejo das TMDs, e revisamos os argumentos que embasam as estratégias de tratamento na EM.
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Twenty-five years since the identification of the first SCA gene: history, clinical features and perspectives for SCA1
ABSTRACT Spinocerebellar ataxias (SCA) are a clinically and genetically heterogeneous group of monogenic diseases that share ataxia and autosomal dominant inheritance as the core features. An important proportion of SCAs are caused by CAG trinucleotide repeat expansions in the coding region of different genes. In addition to genetic heterogeneity, clinical features transcend motor symptoms, including cognitive, electrophysiological and imaging aspects. Despite all the progress in the past 25 years, the mechanisms that determine how neuronal death is mediated by these unstable expansions are still unclear. The aim of this article is to review, from an historical point of view, the first CAG-related ataxia to be genetically described: SCA 1.
RESUMO As ataxias espinocerebelares (SCA) são um grupo clínico e geneticamente heterogêneo de doenças monogênicas que compartilham ataxia e herança autossômica dominante como características principais. Uma proporção importante de SCAs é causada por expansões de repetição de trinucleotídeos CAG na região de codificação de diferentes genes. Além da heterogeneidade genética, os aspectos clínicos transcendem os sintomas motores, incluindo aspectos cognitivos, eletrofisiológicos e de imagem. Apesar de todo o progresso feito nos últimos 25 anos, os mecanismos que determinam como se dá a morte neuronal mediada por essas expansões instáveis ainda não estão claros. O objetivo deste artigo é revisar, de um ponto de vista histórico, a primeira ataxia geneticamente relacionada com o CAG descrita: SCA 1.
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Margaret Dix, Charles Hallpike and the ‘Lagerungs’ Manoeuvre
ABSTRACT The main objective of this manuscript is to describe some personal and professional aspects of two outstanding researchers and pioneers in neuro-otology. Among other achievements, Margaret Ruth Dix, and Charles Skinner Hallpike, designed the most-used provocative test for positional nystagmus for the diagnosis of lithiasis in the vestibular posterior semicircular canal.
RESUMO O principal objetivo desse manuscrito diz respeito a alguns aspectos pessoais e profissionais de dois excelentes pesquisadores e pioneiros da neuro-otologia. Entre outras descrições, Margaret Ruth Dix e Charles Skinner Hallpike descreveram o teste provocativo mais utilizado de nistagmo posicional para o diagnóstico de litíase no canal semicircular posterior do sistema vestibular.
https://ift.tt/2xddFdB
Primary central nervous system post-transplant lymphoproliferative disorder mimicking toxoplasmosis
ABSTRACT The main objective of this manuscript is to describe some personal and professional aspects of two outstanding researchers and pioneers in neuro-otology. Among other achievements, Margaret Ruth Dix, and Charles Skinner Hallpike, designed the most-used provocative test for positional nystagmus for the diagnosis of lithiasis in the vestibular posterior semicircular canal.
RESUMO O principal objetivo desse manuscrito diz respeito a alguns aspectos pessoais e profissionais de dois excelentes pesquisadores e pioneiros da neuro-otologia. Entre outras descrições, Margaret Ruth Dix e Charles Skinner Hallpike descreveram o teste provocativo mais utilizado de nistagmo posicional para o diagnóstico de litíase no canal semicircular posterior do sistema vestibular.
https://ift.tt/2x9dH7j
Added value of arterial spin-labeling (ASL) and susceptibility weighted-images (SWI) in detecting a mild symptomatic intracranial arteriovenous fistula
ABSTRACT The main objective of this manuscript is to describe some personal and professional aspects of two outstanding researchers and pioneers in neuro-otology. Among other achievements, Margaret Ruth Dix, and Charles Skinner Hallpike, designed the most-used provocative test for positional nystagmus for the diagnosis of lithiasis in the vestibular posterior semicircular canal.
RESUMO O principal objetivo desse manuscrito diz respeito a alguns aspectos pessoais e profissionais de dois excelentes pesquisadores e pioneiros da neuro-otologia. Entre outras descrições, Margaret Ruth Dix e Charles Skinner Hallpike descreveram o teste provocativo mais utilizado de nistagmo posicional para o diagnóstico de litíase no canal semicircular posterior do sistema vestibular.
https://ift.tt/2xhBOzI
Perforating palmar disease in TTR-related familial amyloid polyneuropathy
ABSTRACT The main objective of this manuscript is to describe some personal and professional aspects of two outstanding researchers and pioneers in neuro-otology. Among other achievements, Margaret Ruth Dix, and Charles Skinner Hallpike, designed the most-used provocative test for positional nystagmus for the diagnosis of lithiasis in the vestibular posterior semicircular canal.
RESUMO O principal objetivo desse manuscrito diz respeito a alguns aspectos pessoais e profissionais de dois excelentes pesquisadores e pioneiros da neuro-otologia. Entre outras descrições, Margaret Ruth Dix e Charles Skinner Hallpike descreveram o teste provocativo mais utilizado de nistagmo posicional para o diagnóstico de litíase no canal semicircular posterior do sistema vestibular.
https://ift.tt/2xb6bsF
Management of chronic subdural hematoma in Brazil
ABSTRACT The main objective of this manuscript is to describe some personal and professional aspects of two outstanding researchers and pioneers in neuro-otology. Among other achievements, Margaret Ruth Dix, and Charles Skinner Hallpike, designed the most-used provocative test for positional nystagmus for the diagnosis of lithiasis in the vestibular posterior semicircular canal.
RESUMO O principal objetivo desse manuscrito diz respeito a alguns aspectos pessoais e profissionais de dois excelentes pesquisadores e pioneiros da neuro-otologia. Entre outras descrições, Margaret Ruth Dix e Charles Skinner Hallpike descreveram o teste provocativo mais utilizado de nistagmo posicional para o diagnóstico de litíase no canal semicircular posterior do sistema vestibular.
https://ift.tt/2xco6yk
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ABSTRACT The main objective of this manuscript is to describe some personal and professional aspects of two outstanding researchers and pioneers in neuro-otology. Among other achievements, Margaret Ruth Dix, and Charles Skinner Hallpike, designed the most-used provocative test for positional nystagmus for the diagnosis of lithiasis in the vestibular posterior semicircular canal.
RESUMO O principal objetivo desse manuscrito diz respeito a alguns aspectos pessoais e profissionais de dois excelentes pesquisadores e pioneiros da neuro-otologia. Entre outras descrições, Margaret Ruth Dix e Charles Skinner Hallpike descreveram o teste provocativo mais utilizado de nistagmo posicional para o diagnóstico de litíase no canal semicircular posterior do sistema vestibular.
https://ift.tt/2xb66oR
Ryanodine Receptor Open Times Are Determined in the Closed State
The ryanodine receptor (RyR) ion channel releases Ca2+ from intracellular stores by conducting Ca2+ but also by recruiting neighboring RyRs to open, as RyRs are activated by micromolar levels of cytosolic Ca2+. Using long single-RyR recordings of the cardiac isoform (RyR2), we conclude that Ca2+ binding to the cytosolic face of RyR while the channel is closed determines the distribution of open times. This mechanism explains previous findings that RyR is not activated by its own fluxed Ca2+. Our measurements also bolster previous findings that luminal [Ca2+] can affect both the cytosolic activation and inactivation sites and that RyR has different gating modes for the same ionic conditions.
https://ift.tt/2D2157s
Page, Wolfberg & Wirth names new partners
MECHANICSBURG, Pa. — Page, Wolfberg & Wirth ("PWW"), the Nation's leading EMS industry law firm has named Daniel J. Pedersen and Ryan S. Stark as partners in the practice. Mr. Stark and Mr. Pedersen became partners on September 1, 2018 and have assumed additional management and planning responsibilities within the firm. PWW Founding Partner, Doug Wolfberg says,...
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What causes a bump on the roof of the mouth?
A bump can form on the roof of the mouth due to many conditions, including canker sores, mucoceles, torus palatinus, and oral candidiasis. The bump can even be an extra tooth. Most underlying causes are benign, but some require medical treatment. Learn more about the causes and their other symptoms in this article.
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3-D Cell Culture System for Studying Invasion and Evaluating Therapeutics in Bladder Cancer
https://ift.tt/2NICzwa
Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor (LATS) Biosensor
Here we present a luciferase-based biosensor to quantify the kinase activity of large tumor suppressor (LATS)-a central kinase in the Hippo signaling pathway. This biosensor has diverse applications in basic and translational research aimed at investigating Hippo pathway regulators in vitro and in vivo.
https://ift.tt/2Mvf0C8
Arbovirus Infections As Screening Tools for the Identification of Viral Immunomodulators and Host Antiviral Factors
https://ift.tt/2MoYxQ4
CDC: Infant Mortality Rate Varies Greatly Among States
THURSDAY, Sept. 13, 2018 -- Infant mortality rates in the United States vary substantially by state, according to a QuickStats report published in the Aug. 24 issue of the U.S. Centers for Disease Control and Prevention's Morbidity and Mortality...
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AHA: Resistant Hypertension Diagnosis, Tx Guidelines Updated
THURSDAY, Sept. 13, 2018 -- A correct diagnosis of resistant hypertension is necessary to avoid overmedicating, according to a scientific statement from the American Heart Association published online Sept. 13 in Hypertension. Robert M. Carey, M.D.,...
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Pharmacovigilance Needed for Rheumatology Patients
THURSDAY, Sept. 13, 2018 -- Recommendations have been developed for pharmacovigilance in rheumatology, emphasizing the need for continued monitoring of new drugs, according to a position statement issued by the American College of Rheumatology...
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New Risk Score Promising for Predicting MI, Death
THURSDAY, Sept. 13, 2018 -- A score based on the results of three laboratory tests has higher sensitivity and specificity than cardiac troponin alone for stratifying patients presenting with suspected acute coronary syndrome, according to a study...
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Pediatricians Have a Role in Encouraging Play Among Children
THURSDAY, Sept. 13, 2018 -- Pediatricians should encourage parents to ensure their children play, according to a clinical report published in the September issue of Pediatrics. Michael Yogman, M.D., from Harvard University and Mount Auburn Hospital...
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Prurigo Nodularis More Likely in African-Americans
THURSDAY, Sept. 13, 2018 -- African-American patients are more likely to have prurigo nodularis (PN), which is associated with systemic, cardiovascular, and psychiatric comorbidities, according to a study recently published in the Journal of the...
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Physicians Need Training for Mass Casualty Incidents
THURSDAY, Sept. 13, 2018 -- Proper training and post-incident steps can help lessen the secondary trauma health professionals experience providing care during mass casualty incidents (MCIs), according to an article published in the American Medical...
https://ift.tt/2p6K5CQ
Gains in Insurance Coverage Seen for Lesbian, Gay, Bisexual Adults
THURSDAY, Sept. 13, 2018 -- Lesbian, gay, and bisexual (LGB) adults report continued problems affording care despite coverage gains offered by the Affordable Care Act, according to a study published in the August issue of Health Affairs. Kevin H....
https://ift.tt/2CUHaqV
Worse Health Status With Shorter Telomere Length in COPD
THURSDAY, Sept. 13, 2018 -- Patients with chronic obstructive pulmonary disease (COPD) with shorter telomere length have worse health status, according to a study published in the August issue of CHEST. Minhee Jin, from the University of British...
https://ift.tt/2p3JKB2
Risks Posed by Spreading Oil and Gas Wastewater on Roads
THURSDAY, Sept. 13, 2018 -- Spreading oil and gas (O&G) wastewaters on roads may pose human and environmental risks, according to a study recently published in Environmental Science & Technology. Travis L. Tasker, from Pennsylvania State...
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One-Step Approach to Fabricating Polydimethylsiloxane Microfluidic Channels of Different Geometric Sections by Sequential Wet Etching Processes
https://ift.tt/2Nf2Jr2
Genome-wide Surveillance of Transcription Errors in Eukaryotic Organisms
This protocol provides researchers with a new tool to monitor the fidelity of transcription in multiple model organisms.
https://ift.tt/2CToRSY
People Can Infer Which Politicians Are Corrupt From Their Faces
When people are shown photos of politicians they're not familiar with, they can make better-than-chance judgments about whether those politicians have been convicted of corruption, according to research published in Psychological Science, a journal of the Association for Psychological Science.
People can make these judgments even without knowing anything about the politicians or their careers. And one thing they seem to be picking up on is how wide the politicians' faces are.
The individual people making these judgments do only very slightly better than if they were making a random guess (although the difference is statistically significant). However, the judgments become much more accurate when they are combined across a group of people.
Face wideness—technically, the facial width-to-height ratio—has been shown in previous research to be correlated with aggressive behavior in men. That is, men with wider faces have a greater tendency to be aggressive and threatening toward others than do men with thinner faces. Studies have also shown that wide-faced men are perceived by others to be more threatening than men with thinner faces.
The new research is the first to show that observers have a knack for picking out corrupt politicians based on just a portrait and that observers perceive politicians with wider faces as more corruptible.
"It might be difficult to understand why you can look at others' faces and tell something about them," says Chujun Lin, study coauthor and Caltech graduate student. "But there is no doubt that people form first impressions from faces all the time. For example, on dating sites people often reject potential matches based on pictures without reading the profile."
However, it's important to note that the researchers are not claiming that politicians who look corruptible are inherently more corrupt than those who look honest. Their research shows a connection between facial appearance and corruption, but, they say, there could be many explanations. One possibility is that if a face conveys a sense of dishonesty, the politician might be offered bribes more often. Another possibility is that corruptible-looking politicians are not any more corruptible than honest-looking politicians, but because of their looks they are more often suspected of, investigated for, and convicted of corruption.
"If a jury is deciding whether or not a politician is guilty, having a corruptible-looking face might create a negative impression, which might influence the jury's decision," says Lin, who adds that the "clean" politicians used in the study might not actually be clean. "Maybe they just haven't been caught."
The study consisted of four parts.
Part 1: The researchers collected pictures of 72 politicians who held office at the state or federal level. Half had been convicted of corruption and half had clean records. For consistency, all of the politicians included were male and Caucasian. All of the photos were black-and-white; cropped to the same size; and featured a frontal, smiling portrait. The images were presented randomly to 100 volunteers, who were asked to rate each politician on how corruptible, dishonest, selfish, trustworthy, and generous they looked.
An analysis of the data collected showed that the volunteers as a group were able to correctly differentiate the corrupt politicians from the clean politicians nearly 70 percent of the time based on their faces alone.
Part 2: The second part of the study replicated part 1, but used photos of 80 politicians elected to state and local offices in California. Half had violated the California Political Reform Act—a law that regulates campaign finance, lobbying, and politicians' conflicts of interest—and half had clean records. As before, the data showed that the volunteers could correctly differentiate the corrupt politicians from the clean politicians nearly 70 percent of the time.
Part 3: The third part of the study used the images from part 1, but asked the volunteers to judge the politicians on a new set of criteria: corruptibility, aggressiveness, masculinity, competence, and ambitiousness. The data from this study showed that only corruptibility-related trait inferences (inferences of corruptibility, dishonesty, selfishness, aggressiveness, generosity, and trustworthiness) differentiated corrupt politicians from the clean politicians. Inferences of competence, ambitiousness, or masculinity did not predict the politicians' records.
Part 4a: In the fourth section of the study, the researchers examined which of the politicians' facial structures the volunteers associated with dishonesty and corruption. The faces were characterized by eight measures that described things like distance between the eyes, size of the cheekbones, nose length, and face width. By comparing the data from those measures against the judgments made by the volunteers and the records of corruption convictions, the researchers found that politicians with higher facial-width ratios were more likely to be perceived as corruptible.
Part 4b: To double check that face width was truly the characteristic driving negative perceptions about a given politician, the researchers gathered photos of 150 politicians and digitally manipulated each into a wide-faced version and a narrow-faced version. The 450 resulting photos, including the 150 unaltered originals, were shown to 100 participants who were asked, as in the previous studies, to rate each image according to how corruptible the politician seemed. And again, face width made the difference. The volunteers judged the wide-faced versions of the politicians to be more corruptible than their thin-faced counterparts.
"These findings raise many interesting questions for future research," says Lin. "For example, what is the underlying causal mechanism of the correlation between perceived corruptibility and politicians' records found in our study? Are politicians who look more corruptible more likely to be suspected, investigated, and even convicted?"
The findings might make a person wonder why corrupt politicians get elected in the first place if people can tell they're corrupt just by looking at them. Co-author Ralph Adolphs, Bren Professor of Psychology, Neuroscience, and Biology, and director and Allen V. C. Davis and Lenabelle Davis Leadership Chair of the Caltech Brain Imaging Center, says that a lot more than just a face goes into how you feel about a person.
"In the real world, you're not just seeing a photo of a politician. You're seeing them talk and move," says Adolphs, who is also on the leadership team of the Tianqiao and Chrissy Chen Institute for Neuroscience. "Their face might make a first impression on you, but there are other factors that can come in and override that."
Before conducting this study, Lin researched how politicians' facial characteristics relate to their success in elections across different cultures. She plans to continue her research on the judgments people make based on facial structures. Her next study asks volunteers to judge people from all walks of life on 100 different characteristics such as helpfulness, meanness, and healthiness, based on their faces.
Michael Alvarez, a Caltech political science professor, is also a coauthor on the study.
Funding for the research was provided by the Caltech Conte Center for Neurosciences and the National Institute of Mental Health.
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Stroke destination: An opportunity for innovation in system design
Solutions to the transportation decision challenges raised by research like the DAWN trial and DEFUSE-3 trial
https://ift.tt/2CV1M2m
A Neurosphere Assay to Evaluate Endogenous Neural Stem Cell Activation in a Mouse Model of Minimal Spinal Cord Injury
Here, we demonstrate the performance of a minimal spinal cord injury model in an adult mouse that spares the central canal niche housing endogenous neural stem cells (NSCs). We show how the neurosphere assay can be used to quantify activation and migration of definitive and primitive NSCs following injury.
https://ift.tt/2xbi7JX
Standardized Measurement of Nasal Membrane Transepithelial Potential Difference (NPD)
Here, we present a standardized protocol to measure the nasal potential difference (NPD). Cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium channel (ENaC) function are evaluated by the change in the voltage across the nasal epithelium after superfusion of solutions that modify ion channel activity, providing an outcome measure.
https://ift.tt/2NbzaXd
Intraosseous intraneural perineurioma derived from the inferior alveolar nerve with an abnormality of chromosome 22 and expression of the BCR-ABL fusion gene: report of a case and review of recent literature
Abstract
Background
Perineurioma (PN) is a peripheral nerve disease that primarily develops in the limbs and trunk and very rarely occurs in the oral cavity. PN is classified into two types: intraneural perineurioma (INPN) and soft tissue perineurioma (extraneural perineurioma, ENPN). In this article, we report a patient with mandibular body INPN derived from the perineurium of the inferior alveolar nerve.
Case presentation
The patient was a 43-year-old male. He consulted our department for a detailed examination of the right mandibular body. A biopsy was performed at another hospital and he was diagnosed with a schwannoma. At his first visit, hypesthesia extending from the right lower lip to the mental region was recognized and enlargement of the right mandibular canal was confirmed with X-ray CT and MRI. Considering the possibility of future tumor growth, we extirpated the tumor under general anesthesia. Cystic tumor was seen continuously in the inferior alveolar nerve. Immunohistologically, the tumor cells were positive for Glut-1, weakly positive for EMA, and weakly positive for Claudin-1, and the histopathological diagnosis was INPN. In addition, absence of the BCR region of chromosome 22 and expression of the BCR-ABL fusion gene were observed by fluorescent in situ hybridization (FISH), and a chromosome 22 abnormality was confirmed. These findings indicated that the disease was a neoplastic lesion.
Conclusion
Expression of the BCR-ABL fusion gene in INPN that develops in the oral cavity is thought to be very rare, and to the best of our knowledge, ours is the first case to be reported in the literature. About three postoperative years have passed, but findings suggestive of recurrence have not been observed.
https://ift.tt/2NE7vxv
Interstitial Cells in the Pineal Gland of Pregnant and Nonpregnant Viscachas (Lagostomus maximus maximus): A Morphometric and Biochemical Study
The pineal gland of mammals undergoes morphological and biochemical changes throughout the gestation period. In viscachas, a seasonal breeding rodent, pregnancy lasts approximately 154 days and 3 stages can be defined, i.e., early, mid, and late pregnancy. The purpose of this study is to analyze morphometric variations in the expression of S-100 protein, glial fibrillary acidic protein (GFAP), and vimentin in the interstitial cells (IC) in pregnant and nonpregnant viscachas by immunohistochemistry (IHC). We also aim to evaluate a probable relation between glandular activity and pregnancy. The immunopositive percentage area (%IA) for the studied proteins and the number of immunoreactive cells against the S-100 protein with a visible nucleus (nº IC-S-100) were analyzed. Estradiol and progesterone serum levels were also determined by RIA. Variations in the expression of the S-100 protein and GFAP, as well as changes in the nº IC-S-100 related to serum hormone levels, were found between pregnant and nonpregnant viscachas. Viscachas in mid pregnancy exhibited the highest values of %IA for the analyzed proteins, followed by females in late and early pregnancy, while the nonpregnant ones showed the lowest values for all of the groups studied. Likewise, the nº IC-S-100 also varied following the same pattern. Thus, these variations seem to indicate a direct relationship between glandular activity and gonadal hormone levels. On these grounds, we may conclude that IC undergo changes in relation to ovarian hormone levels and participate in the regulation of glandular activity during pregnancy. However, further research is necessary to elucidate this relationship.
Cells Tissues Organs
https://ift.tt/2Og1ILK
Evidence of Cross-Reactivity between Different Seed Storage Proteins from Hazelnut (Corylus avellana) and Walnut (Juglans regia) Using Recombinant Allergen Proteins
Seed storage proteins are extremely stable allergens in nuts, seeds, and legumes and are responsible for the most severe allergic reactions to these foods. The cross-reactivity between seed storage proteins from different sources has not been studied at a molecular level so far. This study aimed to ascertain the cross-reactivity between walnut and hazelnut seed storage proteins using recombinant allergens. Sera from 13 consecutive patients with severe primary walnut and/or hazelnut allergy and hypersensitive to both nuts were studied. IgE specific for rCor a 9, rCor a 14, and rJug r 1 was measured, and inhibition experiments were carried out by measuring IgE reactivity after absorption of patients' sera with freshly prepared walnut extract. All 13 sera showed strong IgE reactivity against walnut 2S albumin, Jug r 1, 12 reacted to hazelnut 2S albumin, Cor a 14, and 8 to the hazelnut legumin, Cor a 9. In inhibition experiments, absorption of sera with whole walnut extract led to the complete disappearance of IgE reactivity to Jug r 1 in 12/13 cases, as expected, but also to the complete disappearance of specific IgE to Cor a 14 in 9/12 sera, and of IgE reactivity to Cor a 9 in 7/8. In the remaining cases a dramatic drop in IgE reactivity was observed. The study shows that patients primarily allergic to either walnut or hazelnut showing a skin or serological reactivity to the other nut also are potentially at risk of severe allergic reactions caused by cross-reactivity between 2S albumins and legumins.
Int Arch Allergy Immunol
https://ift.tt/2x9IuQw
EM Nerd-The Case of the Erroneous Humour
Since the NEJM publication by Pope et al in 2000 found 2% of patients with myocardial infarctions were discharged home from the Emergency Department, we have been in search of a tool capable of identifying a cohort of patients who are truly safe for discharge1. Many have anointed the high-sensitivity troponin assay (hs-cTnI) to this […]
EMCrit Project by Rory Spiegel.
https://ift.tt/2COwpGx
Biological Evaluation of Different Extracts of Aerial Parts of Nepeta deflersiana and Standardization of Active Extracts Using 8-Epi-7-Deoxyloganic Acid and Ursolic Acid by Validated HPTLC Method
Nepeta deflersiana (Lamiaceae) is a well-known medicinal plant that grows in Saudi Arabia. This plant is used in Saudi and Yemeni folk medicine as an anti-inflammatory, carminative, and antirheumatic agent. In order to prove its use in folk medicine, four different extracts from the aerial parts of the plant: petroleum ether, chloroform, ethyl acetate, and n-butanol extracts were subjected to biological assays to screen PPARα and PPARϒ agnostic, antioxidant, anti-inflammatory, and cytotoxic activities. Ethyl acetate and n-butanol extracts of N. deflersiana NDEE and NDBE, respectively, showed a decrease in oxidative stress and inhibition of both NF-kB and iNOS activities with no cytotoxic effects on four human cancer cell lines. Both active extracts were standardized using two bioactive metabolites which were isolated from the aerial parts of the same plant [8-epi-7-deoxyloganic acid (compound 1) and Ursolic acid (compound 2)] by developing a validated HPTLC method. It was found to provide a sharp and compact band of compound 1 at = 0.07 and = 0.57 for compound 2, using chloroform, methanol, and formic acid (8.9:0.8:0.3, v/v/v) as mobile phase at 550 nm. Compounds 1 and 2 were found in NDEE by 9.59 %, w/w, and 84.63 %, w/w, respectively, and by 11.97 %, w/w, and 21.26 %, w/w, respectively, in NDBE.
https://ift.tt/2x8zICY
Comparative Proteomic Analysis of Two Differently Extracted Coptis chinensis in the Treatment of Type 2 Diabetic Rats
Coptis chinensis (CC) is widely used to treat diabetes in traditional Chinese medicine due to its significant hypoglycemic and hypolipidemic effects. It was reported that CC powders are more effective than CC decoctions. In this study, a rat model of type 2 diabetes was established and treated with supercritical-extracted CC and gastric juice extracted CC, respectively. Body weight, fasting plasma insulin, insulin resistance index, and lipid profiles were measured along with oral glucose tolerance tests (OGTTs). In addition, the levels of plasma proteins were compared between type 2 diabetic rats and CC-treated rats using an iTRAQ-based quantitative proteomic analysis. The results showed that the plasma levels of triglyceride (TC), total cholesterol (TG), and low-density lipoprotein (LDL) in rats of both CC-treated groups were significantly decreased. In addition, the proteomic analysis identified 929 proteins, while 15 proteins were selected from these 929 proteins based on their expression levels and bioinformatic results. Among these 15 proteins, 9 proteins (IGF-1, Igfbp4, Igfbp-6, Igfals, C2, C4, Cfi, Prdx-2, and Prdx-3) were upregulated in the two CC-treated groups, while 6 proteins (Pla2g7, Pcyox1, ApoC-1, ApoC-3, ApoB-100, and ApoE) were downregulated. The functions of these proteins are associated with glucose metabolism, insulin action, immunity, inflammation, lipid metabolism, oxidation, and antioxidation. The two differently extracted CC did not show significant differences in terms of their treatment efficacy. This research expanded our understanding on the therapeutic effects and mechanisms of CC in the treatment of type 2 diabetes.
https://ift.tt/2MscM6z
Progress of preoperative and postoperative radiotherapy in gastric cancer
Abstract
Background
Gastric carcinoma, a highly common malignant tumor, is treated mainly by surgery. Meanwhile, radiotherapy is attracting increased attention as a crucial locoregional therapy. However, the application of radiotherapy in gastric carcinoma is still limited and radiation standards remain debatable.
Main body
The use of preoperative radiotherapy for treating gastroesophageal junction cancer has advanced. However, additional phase III clinical trials are needed to further verify the therapeutic value of preoperative radiotherapy for gastric cancer. Patients with D1 or D1 plus lymphadenectomy can benefit from postoperative radiotherapy obviously, and postoperative radiotherapy may be effective for patients with D2 lymphadenectomy with a high N stage. The target volume delineation of preoperative and postoperative radiotherapy should be based on clinical experience and the characteristics of lymphatic drainage.
Conclusions
With the advancement of radiotherapy technology, preoperative and postoperative radiotherapy are becoming increasingly accepted as important auxiliary treatments for gastric cancer.
https://ift.tt/2QrZPNq
Evaluation on prognostic efficacy of lymph nodes ratio (LNR) and log odds of positive lymph nodes (LODDS) in complicated colon cancer: the first study in emergency surgery
Abstract
Background
Lymph node involvement is one of the most important prognostic factors in colon cancer. Twelve is considered the minimum number of lymph nodes necessary to retain reliable tumour staging, but several factors can potentially influence the lymph node harvesting. Emergent surgery for complicated colon cancer (perforation, occlusion, bleeding) could represent an obstacle to reach the benchmark of 12 nodes with an accurate lymphadenectomy. So, an efficient classification system of lymphatic involvement is crucial to define the prognosis, the indication to adjuvant therapy and the follow-up. This is the first study with the aim to evaluate the efficacy of lymph nodes ratio (LNR) and log odds of positive lymph nodes (LODDS) in the prognostic assessment of patients who undergo to urgent surgery for complicated colonic cancer.
Methods
This is a retrospective study carried out on patients who underwent urgent colonic resection for complicated cancer (occlusion, perforation, bleeding, sepsis). We collected clinical, pathological and follow-up data of 320 patients. Two hundred two patients met the inclusion criteria and were distributed into three groups according to parameter N of TNM, LNR and LODDS. Survival analysis was performed by Kaplan-Meier curves, investigating both overall survival (OS) and disease-free survival (DFS).
Results
The median number of harvested lymph nodes was 17. In 78.71% (n = 159) of cases, at least 12 lymph nodes were examined. Regarding OS, significant differences from survival curves emerged for ASA score, surgical indication, tumour grading, T parameter, tumour stage, N parameter, LNR and LODDS. In multivariate analysis, only LODDS was found to be an independent prognostic factor.
Concerning DFS, we found significant differences between survival curves of sex, surgical indication, T parameter, tumour stage, N parameter, LNR and LODDS, but none of these confirmed its prognostic power in multivariate analysis.
Conclusions
We found that N, LNR and LODDS are all related to 5-year OS and DFS with statistical significance, but only LODDS was found to be an independent prognostic factor for OS in multivariate analysis.
https://ift.tt/2OjeLvO
Evaluation of blood flow on the remnant distal bowel during left-sided colectomy
Abstract
Adequate blood flow in anastomosis is of paramount importance to prevent anastomotic leakage. However, it is sometimes difficult to predict the viability of the intestine during surgery. During left-sided colectomy, blood flow on the remnant distal bowel is supplied only from the middle and inferior rectal arteries. The blood backflow after the root ligation of the inferior mesenteric artery is often said to be kept up to promontorium levels; however, this premise is actually based on experience, without reliable evidence. Here, we introduce the intraoperative evaluation of blood flow on the remnant distal bowel during left-sided colectomy using an indocyanine green fluorescence technique.
https://ift.tt/2QuQKDJ
Transcription Factors Drive Tet2-Mediated Enhancer Demethylation to Reprogram Cell Fate
Using a highly efficient reprogramming system, Sardina et al. examined the dynamics of DNA methylation and hydroxymethylation. They found that throughout the process several transcription factors can recruit Tet2 to specific sites, leading to demethylation. Some of these sites became demethylated before chromatin opening.
https://ift.tt/2x8XVZX
The FDA Nozzle Benchmark: In Theory There Is No Difference Between Theory and Practice, But in Practice There Is
International Journal for Numerical Methods in Biomedical Engineering, Volume 0, Issue ja, -Not available-.
https://ift.tt/2x7umI7
Incidence and Considerations of 90 day Readmissions following Posterior Lumbar Fusion
Publication date: Available online 13 September 2018
Source: The Spine Journal
Author(s): Jonathan J. Cui, Raj J. Gala, Nathaniel T. Ondeck, Ryan P. McLynn, Patawut Bovonratwet, Blake Shultz, Jonathan N. Grauer
Abstract
Background Context
Posterior lumbar fusion (PLF) is a commonly performed procedure. The evolution of bundled payment plans is beginning to require physicians to more closely consider patient outcomes up to 90 days after an operation. Current quality metrics and other databases often consider only 30 postoperative days. The relatively new Healthcare Cost and Utilization Project National Readmissions Database (HCUP-NRD) tracks patient-linked hospital admissions data for up to one calendar year.
Purpose
To identify readmission rates within 90 days of discharge following posterior lumbar fusion (PLF) and to put this in context of 30 day readmission and baseline readmission rates.
Study Design
Retrospective study of patients in the HCUP-NRD.
Patient Sample
Any patient undergoing PLF performed in the first 9 months of 2013 were identified in the HCUP-NRD.
Outcome Measures
Readmission patterns up to a full calendar year after discharge. Methods: PLFs performed in the first 9 months of 2013 were identified in the HCUP-NRD. Patient demographics and readmissions were tracked for 90 days after discharge. To estimate the average admission rate in a untreated population, the average daily admission rate in the last quarter of the year was calculated for a subset of PLF patients who had their operation in the first quarter of the year. This study was deemed exempt by the institution's Human Investigation Committee.
Results
Of 26,727 PLFs, 1,580 patients (5.91%) were readmitted within 30 days of discharge and 2,603 patients (9.74%) were readmitted within 90 days of discharge. Of all readmissions within 90 days, 54.56% occurred in the first 30 days. However, if only counting readmissions above the baseline admission rate of a matched population from the 4th quarter of the year (0.08% of population/day), 89.78% of 90 day readmissions occurred within the first 30 days.
Conclusions
The current study delineates readmission rates after PLF and puts this in the context of 30-day readmission rates and baseline readmission rates for those undergoing PLF. These results are important for patient counseling, planning, and preparing for potential bundled payments in spine surgery.
https://ift.tt/2Omu5YM
Frailty and Exercise Training: How to Provide Best Care after Cardiac Surgery or Intervention for Elder Patients with Valvular Heart Disease
The aim of this literature review was to evaluate existing evidence on exercise-based cardiac rehabilitation (CR) as a treatment option for elderly frail patients with valvular heart disease (VHD). Pubmed database was searched for articles between 1980 and January 2018. From 2623 articles screened, 61 on frailty and VHD and 12 on exercise-based training for patients with VHD were included in the analysis. We studied and described frailty assessment in this patient population. Studies reporting results of exercise training in patients after surgical/interventional VHD treatment were analyzed regarding contents and outcomes. The tools for frailty assessment included fried phenotype frailty index and its modifications, multidimensional geriatric assessment, clinical frailty scale, 5-meter walking test, serum albumin levels, and Katz index of activities of daily living. Frailty assessment in CR settings should be based on functional, objective tests and should have similar components as tools for risk assessment (mobility, muscle mass and strength, independence in daily living, cognitive functions, nutrition, and anxiety and depression evaluation). Participating in comprehensive exercise-based CR could improve short- and long-term outcomes (better quality of life, physical and functional capacity) in frail VHD patients. Such CR program should be led by cardiologist, and its content should include (1) exercise training (endurance and strength training to improve muscle mass, strength, balance, and coordination), (2) nutrition counseling, (3) occupational therapy (to improve independency and cognitive function), (4) psychological counseling to ensure psychosocial health, and (5) social worker counseling (to improve independency). Comprehensive CR could help to prevent, restore, and reduce the severity of frailty as well as to improve outcomes for frail VHD patients after surgery or intervention.
https://ift.tt/2Qs60kE
Aortic Arch Variants: A Practical Guide to Safe and Timely Catheterization
Intervent Neurol 2018;7:544–555
https://ift.tt/2N7N3Wc
Analysis of a survey on orthopaedic residency training for fracture treatment in Korea
Publication date: Available online 13 September 2018
Source: Injury
Author(s): Yong-Cheol Yoon, Sang-Hoon Moon, Hyuk-Min Kwon, Jae-Ang Sim, Chang-Wug Oh, Jong-Keon Oh
Abstract
Introduction
Fracture surgery is the most frequently performed orthopaedic procedure and is considered an essential surgical procedure for orthopaedic surgeons in general. Although the approach and circumstances of orthopaedic residency training for fracture treatment may differ between countries, the goals of training, which is to educate the residents regarding the principles of the fracture treatment and foster conscientious orthopaedic specialists, remain unchanged. Thus, the aim of the this study was to determine a desirable course of orthopaedic residency training by investigating and analysing the reality of training associated with fracture surgery and treatment during the orthopaedic residency of 4th year orthopaedic residents in Korea.
Methods
Using a questionnaire survey, a one-on-one interview was proposed to 266 applicants following the secondary board examination of residents who had completed the orthopaedic residency training course; the survey was conducted on January 19, 2016. Responses from 152 applicants (response rate: 57%) who accepted to participate in the survey were statistically analysed.
Results
During residency training, clinicians underwent fracture-related training for 3.5 h on average per month. Training consisted of various approaches and included lectures by professors, case briefings, textbook reading, and field training in an operating room. The residents largely differed in terms of experience in conducting fracture surgery: 47 (31%) responded that they had never performed fracture surgery during the training period, whereas 21 (14%) answered that they had conducted fracture surgery over 20 times. Experience in performing the surgical procedure was the most valuable in fracture training.
Conclusion
To optimize fracture education among orthopaedic residents, the professors at teaching hospitals should understand the realities of fracture education, dedicate sufficient time for internal and external fracture teachings, and allow residents to perform fracture surgeries hands-on under their supervision, and also attempt to foster a social atmosphere that encourages all three factors.
https://ift.tt/2N8exel
Retraction Note: HMGB1: a novel protein that induced platelets active and aggregation via Toll-like receptor-4, NF-κB and cGMP dependent mechanisms
This article [1] is retracted at request of the Editor.
https://ift.tt/2xaXyNF
Retraction Note: Protective role of silymarin in a mouse model of renal Ischemia–Reperfusion injury
This article [1] is retracted at request of the Editor. After publication of this article [1] concerns were raised regarding aspects of the methodology, including the choice of stains being inappropriate or in...
https://ift.tt/2NaUfRp
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
