This study intended to improve physiological characteristics of Magnolia officinalis bark (MOB) extracts by Aspergillus niger fermentation. M. officinalis bark was extracted using distilled water, 95% ethanol, and methanol, and it was then fermented by A. niger. The physiological characteristics of the fermented extracts, namely, tyrosinase inhibitory activity, antioxidant activity, antibacterial activity, and anti-skin-aging activity, were evaluated and compared with those of unfermented extracts. To determine the safety of the fermented extracts, their cytotoxicity was analyzed by measuring the cell viability of CCD-966SK and human epidermal melanocytes (HEMn) after exposure. The fermented methanol extract exhibited the highest antityrosinase activity, total phenolic content, and antioxidant activity. The total phenolic content of the extracts fermented by A. niger was 3.52 times greater than that of the unfermented extracts. The optimal IC50 values for tyrosinase inhibition and 2,2-diphenyl-1-picrylhydrazyl (DPPH) removal by the A. niger-fermented extracts were 30 and 12 μg/mL, respectively. The fermented methanol extracts inhibited skin-aging-related enzymes such as collagenase, elastase, MMP-1, and MMP-2. Compared with the unfermented extracts, the fermented extracts also contained greater antibacterial activity against tested stains including MRSA. These results could be attributed to an increase in the concentration of original active compounds and the biosynthesis of new compounds during fermentation. In cytotoxicity assays, the A. niger-fermented extracts were nontoxic to CCD-966SK cells, even at 500 μg/mL. Hence, in general, methanol-extracted M. officinalis fermented by A. niger for 72 h has the most active antioxidant, skincare, or antiaging compounds for healthy food or cosmetics applications.
https://ift.tt/2DqFsMH
Τετάρτη 14 Νοεμβρίου 2018
Evaluation of Tyrosinase Inhibitory, Antioxidant, Antimicrobial, and Antiaging Activities of Magnolia officinalis Extracts after Aspergillus niger Fermentation
Variation in Identifying Sepsis and Organ Dysfunction Using Administrative Versus Electronic Clinical Data and Impact on Hospital Outcome Comparisons
https://ift.tt/2PtBqdj
The Effect of ICU Diaries on Psychological Outcomes and Quality of Life of Survivors of Critical Illness and Their Relatives: A Systematic Review and Meta-Analysis
https://ift.tt/2QJEVt1
Monoacylglycerol Lipase Inactivation by Using URB602 Mitigates Myocardial Damage in a Rat Model of Cardiac Arrest
https://ift.tt/2PvoHHk
Safety of Percutaneous Dilatational Tracheostomy During Veno-Venous Extracorporeal Membrane Oxygenation Support in Adults With Severe Respiratory Failure
https://ift.tt/2QJLTht
Frequency and intensity of pulmonary bone marrow and fat embolism due to manual or automated chest compressions during cardiopulmonary resuscitation
Abstract
Iatrogenic consequences of cardiopulmonary resuscitation (CPR) include sternal or rib fractures, pulmonary bone marrow embolisms (BME) and fat embolisms (FE). This report aimed to analyze the frequency and intensity of pulmonary BME and FE in fatal cases receiving final CPR efforts with the use of automated chest compression devices (ACCD) or manual chest compressions (mCC). The study cohort (all cardiac causes of death, no ante-mortem fractures) consisted of 15 cases for each group 'ACCD', 'mCC' and 'no CPR'. Lung tissue samples were retrieved and stained with hematoxylin eosin (n = 4 each) and Sudan III (n = 2 each). Evaluation was conducted microscopically for any existence of BME or FE, the frequency of BME-positive vessels, vessel size for BME and the graduation according to Falzi for FE. The data were compared statistically using non-parametric analyses. All groups were matched except for CPR duration (ACCD > mCC) but this time interval was linked to the existence of pulmonary BME (p = 0.031). Both entities occur in less than 25% of all cases following unsuccessful CPR. BME was only detectable in CPR cases, but was similar between ACCD and mCC cases for BME frequency (p = 0.666), BME intensity (p = 0.857) and the size of BME-affected pulmonary vessels (p = 0.075). If any, only mild pulmonary FE (grade I) was diagnosed without differences in the CPR method (p = 0.624). There was a significant correlation between existence of BME and FE (p = 0.043). Given the frequency, intensity and size of pulmonary BME and FE following CPR, these conditions may unlikely be considered as causative for death in case of initial survival but can be found in lower frequencies in autopsy histology.
https://ift.tt/2B6hJQe
Prognostic impact of underlying lung disease in pulmonary wedge resection for lung cancer
Abstract
Background
Pulmonary wedge resection is an option for lung cancer patients with limited cardiopulmonary preservation. As the impact of underlying lung status on the prognosis of such patients remains unclear, we assessed this issue.
Methods
A total of 149 borderline surgical candidates with localized lung cancer who had undergone wedge resection were retrospectively investigated. Clinical variables related to perioperative morbidity, local control rate, and oncological outcomes based on underlying lung disease were analyzed.
Results
According to the risk analysis of postoperative complications, underlying lung disease did not influence the surgical morbidity. Postoperative recurrence occurred in 65 patients (locoregional recurrence in 36, distant metastasis in 12, and both simultaneously in 17). Multivariate analysis revealed that emphysema on computed tomography (CT) [hazard ratio (HR) 0.45; 95% confidence interval (CI) 0.21–0.99] was an independent indicator of locoregional recurrence. Forty-four patients died of lung cancer and 29 of other causes. Multivariate analysis demonstrated that interstitial lung disease on CT (HR 1.98; 95% CI 1.01–3.89) was a predictor of poor prognosis.
Conclusion
Pulmonary wedge resection can be safely undergone by lung cancer patients regardless of pulmonary comorbidity, although underlying lung disease may influence the prognosis after wedge resection.
https://ift.tt/2DJ3PWG
Variation in bucco‐palatal maxillary sinus width does not permit a meaningful sinus classification
Abstract
Objectives
The bucco‐palatal sinus width (SW) appears as relevant factor for graft consolidation after maxillary sinus (MS) floor augmentation. The present study aimed to assess a) SW at different height levels of posterior teeth, b) possible factors influencing SW, and c) whether a simple/meaningful sinus classification based on SW is possible.
Methods
The following parameters were recorded on computed tomographies of 76 edentulous and 86 partially edentulous maxillary quadrants displaying 383 tooth sites in total: i) alveolar ridge height, ii) ‐area, iii) ‐width 2mm apical to the alveolar crest, iv) ‐width at the sinus floor, and v) SW and sinus area at a level 2, 4, 6, 8, and 10mm above the sinus floor. The possible influence of gender, tooth position [i.e., premolar (PM); molar (M)], tooth‐gap extent, and residual alveolar ridge dimensions on SW was assessed. Further, based on percentiles of average values or on the frequency distribution of SW <10, 10‐15, or >15mm, it was attempted to classify the sinus at each given site into narrow, average, or wide.
Results
Gender and tooth‐gap extent presented no relevant impact on MS dimensions; however, significant differences were observed among the various tooth positions regarding all evaluated parameters. The lower the residual alveolar ridge, the wider the MS at 4‐10mm height, while the wider the residual alveolar ridge, the wider the MS. Large variation in SW classes among the different height levels within the same tooth position and among tooth positions within the same person was observed, irrespective of the threshold applied. Further, at a MS height of 10mm at PM1, PM2, M1, and M2, SW was <10mm in 68%, 33%, 0%, and 7% of the cases, respectively, while in 3%, 21%, 65%, and 57%, respectively, SW was >15mm.
Conclusions
There is a large variation in SW depending on the height level within the sinus and on tooth position, which does not permit a simple/meaningful classification of each sinus as "narrow", "average", or "wide". Nevertheless, narrow sinuses (<10mm) are rather prevalent in the premolar region, while wide sinuses (>15mm) in the molar region; further, a wider and shorter residual alveolar ridge is associated with a wider SW.
This article is protected by copyright. All rights reserved.
https://ift.tt/2qPJjuR
Detection of peste des petits ruminants and concurrent secondary diseases in sheep and goats in Ngorongoro district, Tanzania
Abstract
Small ruminants play an important role in the livelihoods of resource-constrained communities. This study was initiated because of a massive outbreak of a respiratory disease in sheep and goats in Loliondo area in Ngorongoro district of Arusha region in Tanzania in 2016. During flock examination, a total of 240 serum samples and 61 nasal swabs were collected. Antibodies to small ruminant morbillivirus, causative agent of peste des petits ruminants (PPR), were detected from sera using a competitive enzyme-linked immunosorbent assay. A multiplex reverse transcription real-time polymerase chain reaction assay was used to detect four pathogens: small ruminant morbillivirus, Mycoplasma capricolum subspecies capripneumoniae, Pasteurella multocida, and Capripoxvirus from the nasal swabs. Overall seroprevalence of PPR was 74.6%, with all four pathogens detected from nasal swabs. Co-infections of small ruminant morbillivirus and Mycoplasma capricolum subspecies capripneumoniae, small ruminant morbillivirus and Capripoxvirus, small ruminant morbillivirus and Pasteurella multocida, and Mycoplasma capricolum subspecies capripneumoniae and Capripoxvirus were also detected. Presence of PPR and the other diseases in this study provided insight into the severity of the outbreak in sheep and goats in Ngorongoro district. Thus, laboratory confirmation is critical for prompt and appropriate interventions to be made for control of diseases in sheep and goats with similar clinical signs. The findings also call for research into development of combined vaccines targeting common diseases of small ruminants in Tanzania.
https://ift.tt/2B7UW6s
Do locally advanced and metastatic human epithelial cancers evolve in ‘placental/decidual-like microenvironments’?
Abstract
Successful tumor microenvironments eventually kill the host. They are not only meant to nourish and protect tumor development, but to give them the right "soil" for perpetual malignant properties such as tissue invasion and metastasis. This can only be achieved if cancers avoid immune vigilance. A similar situation occurs in mammalian placental pregnancy but feto-maternal tolerance is required for a correct physiological process only until birth. Once a cancer microenvironment has acquired the genetic and epigenetic "placental immune editing switches" (PIES) phenotype, it seems likely that it will keep them "available", whenever needed, for the rest of its development, because it gives cellular clones a competitive advantage to pass unnoticed by the host's immune system. This allows primary cancers and their metastasis to continue growing in spite of new and changing antigenic landscapes.
https://ift.tt/2zcdHV1
Assessment of the 8th edition of TNM staging system for gastric cancer: the results from the SEER and a single-institution database
Future Oncology, Ahead of Print.
https://ift.tt/2OMHZ5T
Apalutamide and its use in the treatment of prostate cancer
Future Oncology, Ahead of Print.
https://ift.tt/2zdXgHL
Does race predict the development of metastases in men who receive androgen‐deprivation therapy for a biochemical recurrence after radical prostatectomy?
Background
In this study among men who underwent radical prostatectomy (RP), African American men (AAM) were 28% more likely to develop recurrent disease compared with Caucasian men (CM). However, among those who had nonmetastatic, castration‐resistant prostate cancer (CRPC), race did not predict metastases or overall survival. Whether race predicts metastases among men who receive androgen‐deprivation therapy (ADT) after a biochemical recurrence (BCR) (ie, before CRPC but after BCR) is untested.
Methods
The authors identified 595 AAM and CM who received ADT for a BCR that developed after RP between 1988 and 2015 in the Shared Equal‐Access Regional Cancer Hospital (SEARCH) database. Univariable and multivariable Cox models were used to test the association between race and the time from ADT to metastases. Secondary outcomes included the time to CRPC, all‐cause mortality, and prostate cancer‐specific mortality.
Results
During a median follow‐up of 66 months after ADT, 62 of 354 CM (18%) and 38 of 241 AAM (16%) developed metastases. AAM were younger at the time they received ADT (63 vs 67 years; P < .001), had received ADT in a more recent year (2008 vs 2006; P < .001), had higher prostate‐specific antigen levels at RP (11.1 vs 9.2 ng/mL; P < .001), lower pathologic Gleason scores (P = .004), and less extracapsular extension (38% vs 48%; P = .022). On multivariable analysis, there was no association between race and metastases (hazard radio, 1.20; P = .45) or any of the other secondary outcomes (all P > .5).
Conclusions
Among veterans who received ADT post‐BCR after RP, race was not a predictor of metastases or other adverse outcomes. The current findings suggest that research efforts to understand racial differences in prostate cancer biology should focus on early stages of the disease (ie, closer to the time of diagnosis).
https://ift.tt/2PWTR9T
Regional differences in gallbladder cancer pathogenesis: Insights from a multi‐institutional comparison of tumor mutations
Abstract
Background
Although rare in the United States, gallbladder cancer (GBCA) is a common cause of cancer death in some parts of the world. To investigate regional differences in pathogenesis and outcomes for GBCA, tumor mutations were analyzed from a sampling of specimens.
Methods
Primary tumors from patients with GBCA who were treated in Chile, Japan, and the United States between 1999 and 2016 underwent targeted sequencing of known cancer‐associated genes. Fisher exact and Kruskal‐Wallis tests assessed differences in clinicopathologic and genetic factors. Kaplan‐Meier methods evaluated differences in overall survival from the time of surgery between mutations.
Results
A total of 81 patients were included. Japanese patients (11 patients) were older (median age, 72 years [range, 54‐81 years]) compared with patients from Chile (21 patients; median age, 59 years [range, 32‐73 years]) and the United States (49 patients; median age, 66 years [range, 46‐87 years]) (P = .002) and had more well‐differentiated tumors (46% vs 0% for Chile/United States; P < .001) and fewer gallstone‐associated cancers (36% vs 67% for Chile and 69% for the United States; P = .13). Japanese patients had a median mutation burden of 6 (range, 1‐23) compared with Chile (median mutation burden, 7 [range, 3‐20]) and the United States (median mutation burden, 4 [range, 0‐27]) (P = .006). Tumors from Japanese patients lacked AT‐rich interaction domain 1A (ARID1A) and phosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit alpha (PIK3CA) mutations, whereas Chilean tumors lacked Erb‐B2 receptor tyrosine kinase 3 (ERBB3) and AT‐rich interaction domain 2 (ARID2) mutations. SMAD family member 4 (SMAD4) was found to be mutated similarly across centers (38% in Chile, 36% in Japan, and 27% in the United States; P = .68) and was univariately associated with worse overall survival (median, 10 months vs 25 months; P = .039). At least one potentially actionable gene was found to be altered in 80% of tumors.
Conclusions
Differences in clinicopathologic variables suggest the possibility of distinct GBCA pathogenesis in Japanese patients, which may be supported by differences in mutation pattern. Among all centers, SMAD4 mutations were detected in approximately one‐third of patients and may represent a converging factor associated with worse survival. The majority of patients carried mutations in actionable gene targets, which may inform the design of future trials.
https://ift.tt/2DkB81k
A phase 2 trial of abiraterone acetate without glucocorticoids for men with metastatic castration‐resistant prostate cancer
Abstract
Background
Abiraterone acetate suppresses adrenal androgens and glucocorticoids through the inhibition of CYP17; however, given the risk of mineralocorticoid excess, it is administered with glucocorticoids. Herein, the authors performed a phase 2, single‐arm study that was designed to assess the safety of abiraterone acetate without steroids in patients with castration‐resistant prostate cancer.
Methods
Eligible patients had castration‐resistant prostate cancer with controlled blood pressure and normal potassium. Patients initially received abiraterone acetate at a dose of 1000 mg daily alone. Those with persistent or severe mineralocorticoid toxicity received treatment with prednisone initiated at a dose of 5 mg twice daily. Therapy was continued until radiographic progression, toxicity, or withdrawal. The primary objective of the current study was to determine the percentage of men requiring prednisone to manage mineralocorticoid toxicity. Toxicity was graded according to Common Terminology Criteria for Adverse Events, version 4.0.
Results
A total of 58 patients received at least 1 dose of abiraterone acetate; the majority had metastases (53 patients; 91.4%). Sixteen patients (27.6%) received prior chemotherapy, 6 patients (10.3%) received prior enzalutamide, and 4 patients (7%) received prior ketoconazole. Grade 3 to 4 adverse events of interest included hypertension (9 patients; 15.5%) and hypokalemia (4 patients; 7%). There was no grade ≥3 edema. Seven patients (12%) initiated prednisone therapy for mineralocorticoid toxicity, 3 patients for hypertension (5%), and 4 patients for hypokalemia (7%). Two patients initiated prednisone therapy for fatigue (3%). Forty patients (68%) experienced a decline in prostate‐specific antigen of ≥50% with the use of abiraterone acetate alone. Patients with lower baseline levels of androstenedione (P = .04), androsterone (P = .01), dehydroepiandrosterone (P = .03), and 17‐hydroxyprogesterone (P = .03) were found to be more likely to develop mineralocorticoid toxicity.
Conclusions
Treatment with abiraterone acetate without steroids is feasible, although clinically significant adverse events can occur in a minority of patients. The use of abiraterone acetate without prednisone should be balanced with the potential for toxicity and requires close monitoring.
https://ift.tt/2PYHUjY
Weight Reduction and Pioglitazone are Cost-Effective for the Treatment of Non-Alcoholic Fatty Liver Disease in Thailand
Abstract
Introduction
This study evaluated lifetime liver-related clinical outcomes, costs of treatment, and the cost-effectiveness of treatment options for non-alcoholic fatty liver disease (NAFLD) in Thailand.
Methods
A cost-utility analysis using a lifetime Markov model was conducted among Thai patients with NAFLD, from a societal perspective. Pioglitazone, vitamin E, a weight reduction program, and usual care were investigated, with the outcomes of interest being the number of cirrhosis and hepatocellular carcinoma (HCC) cases, life expectancy, quality-adjusted life-years (QALYs), lifetime costs, and the incremental cost-effectiveness ratios (ICERs). One-way and probabilistic sensitivity analyses were performed.
Results
When compared with usual care, a weight reduction program can prevent cirrhosis and HCC cases by 13.91% (95% credible interval [CrI] 0.97, 20.59) and 2.12% (95% CrI 0.43, 4.56), respectively; pioglitazone can prevent cirrhosis and HCC cases by 9.30% (95% CrI −2.52, 15.24) and 1.42% (95% CrI −0.18, 3.74), respectively; and vitamin E can prevent cirrhosis and HCC cases by 7.32% (95% CrI −4.64, 15.56) and 1.12% (95% CrI −0.81, 3.44), respectively. Estimated incremental life expectancy and incremental QALYs for all treatment options compared with usual care were approximately 0.06 years and 0.07 QALYs, respectively. The lifetime costs of both a weight reduction program and pioglitazone were less than usual care, while vitamin E was $3050 (95% CrI 2354, 3650). The weight reduction program dominated all other treatment options. The probability of being cost-effective in Thailand's willingness-to-pay threshold ($4546/QALY gained) was 76% for the weight reduction program, 22% for pioglitazone, 2% for usual care, and 0% for vitamin E.
Conclusions
A weight reduction program can prevent cirrhosis and HCC occurrences, and dominates all other treatment options. Pioglitazone and vitamin E demonstrated a trend towards decreasing the number of cirrhosis and HCC cases.
https://ift.tt/2K5nCzR
Mesenteric Panniculitis With Lupus Demonstrated on 18F-FDG PET/CT
We describe the 18F-FDG PET/CT findings in a rare case of mesenteric panniculitis caused by systemic lupus. A previous CT had raised suspicion of a space-occupying lesion in the left hypochondrium in a context of aspecific constitutional symptoms and inflammatory parameters. The diagnosis of panniculitis was confirmed at laparoscopic biopsy directed by the PET findings. Follow-up 18F-FDG PET/CT after 1 month of corticosteroid therapy showed complete disappearance of the abdominal hypermetabolic foci.https://ift.tt/2qJVd9K
Increased Activity Due to Fractures Does Not Significantly Affect the Accuracy of 68Ga-DOTATATE PET/CT in the Detection of Culprit Tumor in the Evaluation of Tumor-Induced Osteomalacia
Objective 68Ga-DOTATATE PET/CT is currently the most common imaging modality in localizing culprit tumors, which can result in tumor-induced osteomalacia (TIO). Fracture, which is one of the most common consequences of the TIO, can also lead to increased 68Ga-DOTATATE activity and potentially affect the accuracy of 68Ga-DOTATATE PET/CT imaging. The aim of this investigation is to evaluate whether the increased 68Ga-DOTATATE activity at the sites of the fracture will cause interpretation difficulty in the localizing the culprit tumor causing TIO. Method The images of 68Ga-DOTATATE PET/CT scan from a total of 54 patients who had multiple foci of increased 68Ga-DOTATATE PET/CT on PET/CT were retrospectively analyzed. Not only was the intensity of the activity on PET but also the appearance of the activity on CT taken into consideration when the interpretation of the images occurred. The results from imaging analysis were compared with the clinical chart record. All patients had tentative clinical diagnosis of TIO. Results The causative tumors in 53 patients were eventually identified. In 1 patient, the causative tumor was not identified. Among the 53 patients with confirmed TIO, 52 tumors were accurately localized. Conclusions Mild activity at the sites of fracture is not a major challenging factor in the interpretation of 68Ga-DOTATATE PET/CT in the evaluation of TIO when both intensity on PET and morphology on CT were assessed.https://ift.tt/2Fq68Q5
Splenosis of the Liver Capsule
Splenosis, a form of ectopic splenic tissue, is generally caused by heterotopic autotransplantation of splenic tissues after traumatic splenic rupture or splenectomy. The implants are often localized intraperitoneally, mostly in the left upper quadrant and splenic region. Hepatic foci are seen only on rare occasions. The differential diagnosis of splenosis foci from malignant masses can be challenging by conventional imaging and lead to unnecessary invasive procedures. This manuscript presents radiological and scintigraphic images of splenosis foci located in the peritoneal cavity and liver capsule of a 46-year-old man who underwent splenectomy due to traumatic splenic rupture 30 years ago.https://ift.tt/2qLtjtZ
Prognostic Value of Volumetric Parameters of Pretreatment 18F-FDG PET/CT in Esophageal Cancer: A Systematic Review and Meta-analysis
Purpose We performed a systematic review and meta-analysis on the prognostic value of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) derived from pretreatment 18F-FDG PET/CT in patients with esophageal cancer. Methods PubMed and EMBASE databases were searched until April 12, 2018, for studies that evaluated MTV or TLG as prognostic factors in esophageal cancer, with overall survival (OS) and event-free survival serving as the end points. Hazard ratios (HRs) were meta-analytically pooled using a random-effects model. Subgroup analyses based on the clinicopathological and PET variables were performed. Results In total, 16 studies with 1294 patients were included. The pooled HRs of MTV and TLG for OS were 2.26 (95% confidence interval [CI], 1.73–2.96) and 2.23 (95% CI, 1.73–2.87), respectively. Regarding event-free survival, the pooled HRs of MTV and TLG were 2.03 (95% CI, 1.66–2.49) and 2.57 (95% CI, 1.82–3.62), respectively. Metabolic tumor volume was found to be a significant prognostic factor for OS consistently across multiple subgroups classified based on stage, histological subtype, treatment, delineation of volume of interest, and the determination method of cutoff value, with pooled HRs ranging from 1.96 to 2.54. Conclusions In patients with esophageal cancer, MTV and TLG derived from pretreatment 18F-FDG PET are significant prognostic factors. As prognostic biomarkers, volumetric metabolic parameters may bolster the role of 18F-FDG PET in the management of esophageal cancer.https://ift.tt/2FpBpTr
Update 2018: 18F-FDG PET/CT and PET/MRI in Head and Neck Cancer
There are recent advances, namely, a standardized method for reporting therapy response (Hopkins criteria), a multicenter prospective cohort study with excellent negative predictive value of 18F-FDG PET/CT for N0 clinical neck, a phase III multicenter randomized controlled study establishing the value of a negative posttherapy 18F-FDG PET/CT for patient management, a phase II randomized controlled study demonstrating radiation dose reduction strategies for human papilloma virus–related disease, and Food and Drug Administration approval of nivolumab for treatment of recurrent head and neck squamous cell carcinoma.https://ift.tt/2qMj9t2
ACR Practice Parameter for the Performance of Gallium-68 DOTATATE PET/CT for Neuroendocrine Tumors
https://ift.tt/2Flpo1d
Gastric GIST Incidentally Detected on 68Ga-PSMA-PET/CT: Correlation Between Functional Imaging and Histology
Prostate-specific membrane antigen (PSMA) is specific for prostate cancer cells; nevertheless when finding uptake in abnormal locations for prostate cancer metastases, it is important to consider other hypothesis, including second cancers. There are several papers about PSMA expression in many different types of cancer, but few reported expression in gastrointestinal stromal tumors (GIST). In this case, we documented the GIST lesion not only by PET/CT but also by gastroscopy and histology. Additionally, PSMA immunochemistry was performed, showing PSMA expression in tumoral GIST cells (not in endothelial cells), evidencing a good correlation between PET/CT image and histology.https://ift.tt/2qKpPrH
ACR–ACNM Practice Parameter for the Performance of Fluorine-18 Fluciclovine-PET/CT for Recurrent Prostate Cancer
https://ift.tt/2FkFisM
Thyroid Metastasis From Hepatocellular Carcinoma Visualized by 18F-FDG PET/CT Imaging
Thyroid metastasis from hepatocellular carcinoma (HCC) is very rare. We present a case of a 41-year-old man with a markedly elevated serum α-fetoprotein (2,297 ng/mL) and a left neck mass 6 months after a hepatolobectomy for a primary HCC. 18F-FDG PET/CT imaging showed a focal uptake in the left thyroid lobe corresponding to a mass. The patient underwent a left hemithyroidectomy. Subsequent pathology confirmed HCC metastasis to the thyroid.https://ift.tt/2qNC9r5
Incidental Detection of Skeletal Metastases on 99mTc-DTPA Renography
We present the case of a 53-year-old man with left hydroureteronephrosis who underwent 99mTc-DTPA renography for functional assessment of bilateral kidneys. 99mTc-DTPA renography of the patient showed diffusely increased extrarenal 99mTc-DTPA uptake in the visualized lumbosacral vertebrae and in the pelvic bones, on the blood flow and functional phase of the renography, which was suggestive of disseminated skeletal disease. Subsequent MRI lumbosacral spine and 18F-FDG PET/CT revealed extensive skeletal metastases corresponding to the increased extrarenal 99mTc-DTPA uptake in the lumbosacral vertebrae and the pelvic bones from primary left lung mitotic lesion.https://ift.tt/2Fq66Yt
18F-FDG Uptake in Subcutaneous Fat Preceding Clinical Diagnosis of Human Immunodeficiency Virus–Associated Lipodystrophy
A 62-year-old man with human immunodeficiency virus (HIV) on long-standing highly active antiretroviral therapy presented for 18F-FDG PET/CT evaluation of a pulmonary nodule. The examination showed unusual radiotracer distribution accumulating in the subcutaneous and visceral fat with low cerebral and skeletal muscle uptake. Imaging features were consistent with HIV-associated lipodystrophy, an unsuspected diagnosis that was later confirmed on physical examination. Recognition of HIV-associated lipodystrophy by the nuclear medicine physician is critical as altered biodistribution may affect diagnostic yield or be mistaken for infectious pathology.https://ift.tt/2qOmdFe
FDG PET/CT in a Case of Dural Amyloidoma
Dural amyloidoma is an unusual presentation of central nervous system amyloidosis. A 49-year-old woman presented with 1-month history of repeated episodes of vertigo. Precontrast MRI showed dural thickening over right frontal convexity with signal intensity similar to white matter. Postcontrast T1-weighted images showed remarkable enhancement of the lesion. Dural amyloidoma was confirmed by partial resection of the lesion. The patient underwent no further treatment. A follow-up FDG PET/CT showed increased FDG uptake of the residual dural amyloidoma. This case indicates dural amyloidoma should be included in the differential diagnosis of abnormal FDG uptake in dural lesions.https://ift.tt/2FwHrkS
18F-NaF PET/CT in Prostatic Calculi
Primary prostatic calculi commonly present asymptomatically in men over the age of 50 years. Individual calculi form when the secretory tube is blocked by inflammation, prostatic secretions, or corpora amylacea. Although small prostatic calculi have been described as a component of normal aging, increased prevalence of calculi has been associated with benign prostatic hyperplasia and prostatitis. We are presenting prostatic calcification in a 69-year-old man as incidentally detected on 18F-NaF PET/CT. Although previous publications have reported 18F-NaF uptake portraying calcification in soft tissue, these findings demonstrate a new domain in which to assess calcium metabolism using 18F-NaF PET/CT.https://ift.tt/2qOmN5S
Hypermetabolism Caused by Seizure Mimicking Tumor Recurrence
A 41-year-old man had a right frontal grade I glioma resection 17 years ago. He was tumor free since. However, 1 month ago, he presented with an uncontrollable seizure, which raised the possibility of recurrent tumor. The 18FDG PET/CT brain scan showed increased tracer uptake at the margin of the previous resected tumor, suggesting the possibility of tumor recurrence. However, on a repeat FDG PET brain scan confirmed by electroencephalography monitory as an interictal study, no elevated FDG uptake was revealed at this site. These results indicate that the elevated 18F-FDG activity on the original study was a result of seizure.https://ift.tt/2FwO9HY
Pretreatment Primary Tumor and Nodal SUVmax Values on 18F-FDG PET/CT Images Predict Prognosis in Patients With Salivary Gland Carcinoma
Purpose To assess whether primary tumor and nodal 18F-FDG uptake may predict prognosis in patients with salivary gland carcinoma. Methods We conducted a 2-center, retrospective study on 117 patients with salivary gland carcinoma who underwent 18F-FDG PET/CT before treatment and were subsequently treated with curative intent between 2004 and 2014. Pretreatment SUVmax of the primary tumor (SUVmax-T) and that of positive nodes (SUVmax-N) were analyzed in relation to clinical outcomes. Results Patients were followed up for a median of 61 months. The following 5-year rates were observed: locoregional control (LRC), 78%; distant metastasis-free survival (DMFS), 67%; progression-free survival (PFS), 62%; and overall survival (OS), 68%. A cutoff value of 7.0 maximized the prognostic impact of both SUVmax-T and SUVmax-N for PFS. Compared with patients with SUVmax-T and SUVmax-N values below the optimal cutoff, those with SUVmax-T and SUVmax-N of 7 or greater showed less favorable 5-year LRC (Phttps://ift.tt/2qNC7zt
Unexpected Corpus Callosum Involvement of Diffuse Large B-Cell Lymphoma on FDG PET/CT
Diffuse large B-cell lymphoma (DLBCL) was the most frequent subtype of lymphoid malignancy. Corpus callosum involvement of DLBCL was rarely reported. We present a case of DLBCL involving not only lymph nodes and bowels but also corpus callosum, detected by FDG PET/CT in a patient without neurological symptoms. After 4 cycles of systemic and intrathecal chemotherapy, all previously visualized abnormal activity disappeared on the follow-up FDG PET/CT.https://ift.tt/2FmYSEu
Fine-Scale Resolution of Runs of Homozygosity Reveal Patterns of Inbreeding and Substantial Overlap with Recessive Disease Genotypes in Domestic Dogs
Inbreeding leaves distinct genomic traces, most notably long genomic tracts that are identical by descent and completely homozygous. These runs of homozygosity (ROH) can contribute to inbreeding depression if they contain deleterious variants that are fully or partially recessive. Several lines of evidence have been used to show that long (> 5 megabase) ROH are disproportionately likely to harbor deleterious variation, but the extent to which long versus short tracts contribute to autozygosity at loci known to be deleterious and recessive has not been studied. In domestic dogs, nearly 200 mutations are known to cause recessive diseases, most of which can be efficiently assayed using SNP arrays. By examining genome-wide data from over 200,000 markers, including 150 recessive disease variants, we built high-resolution ROH density maps for nearly 2,500 dogs, recording ROH down to 500 kilobases. We observed over 678 homozygous deleterious recessive genotypes in the panel across 29 loci, 90% of which overlapped with ROH inferred by GERMLINE. Although most of these genotypes were contained in ROH over 5 Mb in length, 14% were contained in short (0.5 - 2.5 megabase) tracts, a significant enrichment compared to the genetic background, suggesting that even short tracts are useful for computing inbreeding metrics like the coefficient of inbreeding estimated from ROH (FROH). In our dataset, FROH differed significantly both within and among dog breeds. All breeds harbored some regions of reduced genetic diversity due to drift or selective sweeps, but the degree of inbreeding and the proportion of inbreeding caused by short versus long tracts differed between breeds, reflecting their different population histories. Although only available for a few species, large genome-wide datasets including recessive disease variants hold particular promise not only for disentangling the genetic architecture of inbreeding depression, but also evaluating and improving upon current approaches for detecting ROH.
https://ift.tt/2FzVnej
Short Term Androgen Deprivation Therapy Without or With Pelvic Lymph Node Treatment Added to Prostate Bed Only Salvage Radiotherapy: The NRG Oncology/RTOG 0534 SPPORT Trial
To determine in a three-arm randomized trial whether there are incremental gains in freedom from progression (FFP) from the addition of 4-6 months of short term androgen deprivation therapy (STADT) using antiandrogen plus an LHRH agonist, without or with pelvic lymph node treatment (PLNRT), to prostate bed salvage radiotherapy (PBRT).
https://ift.tt/2RTsQBk
Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-associated Oropharyngeal Cancer
To assess the performance of plasma circulating tumor HPV DNA (ctHPVDNA) as a surveillance blood test in patients with p16 positive oropharyngeal squamous cell carcinoma (OPSCC).
https://ift.tt/2DEn6bO
Erratum to: Tsang RW, Campbell BA, Goda JS et al. Radiation Therapy for Solitary Plasmacytoma and Multiple Myeloma: Guidelines From the International Lymphoma Radiation Oncology Group. Int J Radiat Oncol Biol Phys 2018;101: 794-808.
It should be noted that Dr. Peter M. Mauch has passed away on September 8, 2017. Despite his illness, he participated in the ILROG Guidelines Retreat that took place in Boston from March 2-4, 2017, and played a key role in ensuring its success. Several ILROG guidelines have since been published or in the process of being completed. ILROG is grateful to Dr. Mauch's deep commitment and contributions to the group.
https://ift.tt/2DCGCFu
Controversy in the Treatment of Localized Hepatocellular Carcinoma
A 75-year-old man was found to have a solitary liver mass concerning for hepatocellular carcinoma (HCC). His medical history was notable for obesity, type 2 diabetes, and nonalcoholic fatty liver disease. A computed tomography scan of the abdomen was performed for abdominal pain and showed a 4.5 cm mass in the liver. Laboratory evaluation revealed total bilirubin 1.1 mg/dL, albumin 4.5 g/dL, prothrombin time 12.5 seconds, creatinine 1.2 mg/dL, platelets 199, and alpha fetoprotein 36 ng/mL. Magnetic resonance imaging of the abdomen showed a 4.5 cm mass in segment 6/7 of the liver demonstrating early arterial enhancement with delayed washout and a pseudocapsule, meeting imaging criteria for HCC (Fig. 1).
https://ift.tt/2RWUnSI
Erratum to: Gunther JR, Jimenez RB, Yechieli RL, et al. Introductory Radiation Oncology Curriculum: Report of a National Needs Assessment and Multi-institutional Pilot Implementation. Int J Radiat Oncol Biol Phys 2018;101:1029-1038.
The published manuscript did not denote the equivalent first author contributions of Drs. Gunther and Jimenez nor the equivalent senior author contribution of Drs. Fields and Golden. The corrected manuscript should convey first authorship to both Drs. Gunther and Jimenez and senior authorship to both Drs. Fields and Golden.
https://ift.tt/2ROXj3I
Act.in.Sarc: An International Randomized Phase III Trial Evaluating Efficacy and Safety of First-in-Class NBTXR3 Hafnium Oxide Nanoparticles Activated By Preoperative Radiotherapy in Locally Advanced Soft Tissue Sarcoma
A subset of soft tissue sarcoma (STS) patients achieve significant therapeutic benefit from preoperative radiotherapy (RT). Yet, this treatment paradigm may be associated with limited efficacy and increased toxicity, highlighting the necessity of novel multimodal therapies aimed at local control with few adverse events (AEs). NBTXR3 is a first-in-class Hafnium-Oxide nanoparticle. Designed for cancer cell uptake, it is injected intratumorally (IT) and activated by ionizing radiation to yield a tumor-localized high energy deposit and increased cell death compared to the same dose of RT alone.
https://ift.tt/2DDKZ3f
In Reply to Wilkins et al
To the Editor: Thank you to Dr. Wilkins and colleagues for the clarifications provided in your response (1) to my recent editorial (2) on your article (3). I am sure the readership appreciates your valuable added insights, but I still unfortunately believe my original comments regarding the limitations of Ki-67 as a prognostic biomarker hold true. I fully understand that you analyzed Ki-67 as a continuous variable and the interpretation of the hazard ratio estimate. Although assessing Ki-67 as a continuous variable maximizes statistical power, it also has notable downsides, especially with a biomarker like Ki-67.
https://ift.tt/2RVlBZQ
Preservation of Neurocognitive Function (NCF) with Conformal Avoidance of the Hippocampus during Whole-Brain Radiotherapy (HA-WBRT) for Brain Metastases: Preliminary Results of Phase III Trial NRG Oncology CC001
Based on preliminary evidence that radiation to the neuroregenerative hippocampal stem cells plays a role in NCF decline, the phase II NRG/RTOG 0933 trial demonstrated memory-preservation following HA-WBRT. The phase III NRG-CC001 trial of WBRT plus memantine without (WBRT+M) or with hippocampal avoidance (HA-WBRT+M) sought to validate these findings.
https://ift.tt/2DFkMkU
In Regard to Bauer-Nilsen et al
To the Editor: The work of Bauer-Nilsen et al explores time-driven activity-based cost (TDABC) and reimbursement of cervical cancer radiation therapy (1). The authors propose that high TDABC but low reimbursement could contribute to the declining use of brachytherapy. Overall, the analysis was intriguing and generated discussion among the American Society for Radiation Oncology's Code Development and Valuation Sub-Committee, which analyzes reimbursement for radiation oncology services. Although TDABC may be useful in better understanding practice cost drivers, there are limitations in the analysis that prevent generalizability and direct comparisons to Centers for Medicare and Medicaid Services payment determinations.
https://ift.tt/2RWUtty
PACIFIC: Overall Survival with Durvalumab versus Placebo after Chemoradiotherapy in Stage III NSCLC
In the global, Phase 3 PACIFIC study (Antonia 2017; NCT02125461), durvalumab significantly improved progression-free survival (PFS) versus placebo in Stage III, unresectable NSCLC patients without progression after concurrent chemoradiotherapy (CRT) (stratified HR, 0.52; 95% CI, 0.42–0.65; P<0.001). This was the first major advance in this disease setting for many years. Here we report the second primary endpoint of overall survival (OS) for PACIFIC.
https://ift.tt/2DHUEFO
In Regard to Valdes et al
To the Editor: We read with interest the article by Valdes et al in which machine learning methods were used to predict biochemical failure after salvage brachytherapy for prostate cancer (1). Although the article addresses a relevant clinical issue, we are concerned that there are issues with the statistical methods that undermine the conclusion of good predictive performance. Given the many recent papers in our field applying machine learning to clinical questions, the themes discussed in this letter may apply more broadly.
https://ift.tt/2RWUqxS
HCC in Cirrhotics With Retained Liver Function and Absent Portal Hypertension: Still a Surgical Disease
This patient is presenting with a single lesion and retained liver function (1). He is noted to have a Childs-Turcotte-Pugh score of A5, and his calculated Model for End-Stage Liver Disease score (assuming a normal sodium level) is 10, predicting a 90-day mortality of 6% from a liver disease standpoint. Importantly, there is no evidence of portal hypertension. Based on one of the most commonly used hepatocellular carcinoma staging systems, the Barcelona Clinic Liver Cancer staging system, he has early stage Barcelona Clinic Liver Cancer-A disease (2).
https://ift.tt/2DFWmHY
TACE-Ablate Approach to Treatment of a Solitary HCC
Transarterial chemoembolization, combined with thermal ablation, is likely to provide the most durable response for this patient (1, 2). Although surgical resection is potentially curative, portal hypertension may preclude resection at many centers. This hepatocellular carcinoma is peripheral and favorable for ablation, but its size (>3 cm) makes curative ablation more challenging to achieve. Complete necrosis rates in the radiofrequency ablation literature decrease as the lesion size increases to greater than 3 cm.
https://ift.tt/2DFWhUG
Randomized Trial Evaluating Radiation following Surgical Excision for “Good Risk” DCIS: 12-Year Report from NRG/RTOG 9804
NRG/RTOG 9804 is the only prospective randomized trial to assess the impact of whole breast radiation (WBRT) versus observation (OBS) in women with "good risk" DCIS, following breast conservation surgery. The primary objective is local recurrence (LR) in the treated breast. Long-term results of this trial are presented here.
https://ift.tt/2RPijqQ
NRG-RTOG 1016: Phase III Trial Comparing Radiation/Cetuximab to Radiation/Cisplatin in HPV-related Cancer of the Oropharynx
To determine whether radiation with cetuximab has non-inferior overall survival compared to radiation with cisplatin in patients with locoregionally advanced human papillomavirus (HPV)–related oropharynx cancer.
https://ift.tt/2RWUxJO
The Case for Proton Beam Therapy
This patient with Barcelona Clinic Liver Cancer stage A hepatocellular carcinoma (HCC) in the setting of nonalcoholic fatty liver disease–related Child-Pugh A5 cirrhosis should be strongly considered for definitive hypofractionated proton beam therapy (PBT) (1). The physical characteristics of protons make them particularly attractive and well suited for treatment of patients with HCC. PBT deposits the majority of dose at the Bragg peak with little to no exit dose, which is beneficial for patients with HCC because of the radiosensitivity of the normal liver, especially to low doses.
https://ift.tt/2DFWabI
FLI1 exonic circular RNAs as a novel oncogenic driver to promote tumor metastasis in small cell lung cancer
Purpose: The aberrantly upregulated Friend leukemia virus integration 1 (FLI1) is closely correlated with the malignant phenotype of small cell lung cancer (SCLC). This study attempts to examine if FLI1 exonic circular RNAs (FECRs) function as a new malignant driver that determines the metastatic phenotype in SCLC. Experimental Design: The expression of FECRs was examined in SCLC tissues and serum exosomes. The oncogenic activity of FECRs was investigated in SCLC cell lines and animal xenograft studies. Finally, we explored the molecular mechanisms underlying these non-coding RNAs as a malignant driver. Results: Therapeutic comparison of CRISPR Cas9 knockout and shRNA knockdown of FLI1 identified FECRs as a new non-canonical malignant driver in SCLC. We found that FECRs were aberrantly upregulated in SCLC tissues (p<0.0001), and was positively associated with lymph node metastasis (p<0.01). Notably, serum exosomal FECR1 was associated with poor survival and clinical response to chemotherapy. Silencing of FECRs significantly inhibited the migration in two highly aggressive SCLC cell lines and reduced tumor burden in a mouse xenograft model. Mechanistically, we uncovered that FECRs sequestered and subsequently inactivated tumor suppressor microRNA miR584-3p, leading to the activation of the Rho Associated Coiled-Coil Containing Protein Kinase 1 gene (ROCK1). Conclusion: This study identifies FLI1 exonic circular RNAs as a new oncogenic driver that promotes tumor metastasis through the miR584-ROCK1 pathway. Importantly, serum exosomal FECR1 may serve as a promising biomarker to track disease progression of SCLC.
https://ift.tt/2B7lEfn
Inhibition of BUB1 Kinase by BAY 1816032 Sensitizes Tumor Cells towards Taxanes, ATR and PARP Inhibitors in vitro and in vivo
Purpose: The catalytic function of BUB1 is required for chromosome arm resolution and positioning of the chromosomal passenger complex for resolution of spindle attachment errors and plays only a minor role in spindle assembly checkpoint activation. Here we present the identification and preclinical pharmacological profile of the first BUB1 kinase inhibitor with good bioavailability. Experimental Design: The Bayer compound library was screened for BUB1 kinase inhibitors and medicinal chemistry efforts to improve target affinity, physicochemical and pharmacokinetic parameters resulting in the identification of BAY 1816032 were performed. BAY 1816032 was characterized for kinase selectivity, inhibition of BUB1 signalling, and inhibition of tumor cell proliferation alone and in combination with taxanes, ATR and PARP inhibitors. Effects on tumor growth in vivo were evaluated using human triple-negative breast xenograft models. Results: The highly selective compound BAY 1816032 showed long target residence time and induced chromosome mis-segregation upon combination with low concentrations of paclitaxel. It was synergistic or additive in combination with paclitaxel or docetaxel, as well as with ATR or PARP inhibitors in cellular assays. Tumor xenograft studies demonstrated a strong and statistically significant reduction of tumor size and excellent tolerability upon combination of BAY 1816032 with paclitaxel or olaparib as compared to the respective monotherapies. Conclusions:Our findings suggest clinical proof of concept studies evaluating BAY 1816032 in combination with taxanes or PARP inhibitors in order to enhance their efficacy and potentially overcome resistance.
https://ift.tt/2K7hy9W
More is more: Semi-annual breast MRI screening in BRCA1 mutation carriers
Although annual MRI-screening has improved early diagnosis of hereditary breast-cancer, fast growth-rates of BRCA1-associated cancers can still lead to interval cancers, and/or node-positive disease. Using MRI with shorter screening intervals helps to effectively avoid both, interval cancers and node-positive stages, whereas there is no role for mammography in these women.
https://ift.tt/2B6rL3E
Capivasertib Active against AKT1-Mutated Cancers [News in Brief]
Pan-AKT inhibitor shrinks breast and gynecologic tumors—and shows efficacy against some rare cancers.
https://ift.tt/2FnFiIs
Capmatinib Triggers Responses in NSCLC [News in Brief]
MET inhibitor shrinks tumors, shows activity against brain metastases in patients with advanced disease.
https://ift.tt/2qLrJbp
Fraud in the field: Signature compliance
EMS providers should be on high alert for fraud and forgery in the patient care report
https://ift.tt/2TesCGL
High-affinity CD16-polymorphism and Fc-engineered antibodies enable activity of CD16-chimeric antigen receptor-modified T cells for cancer therapy
High-affinity CD16-polymorphism and Fc-engineered antibodies enable activity of CD16-chimeric antigen receptor-modified T cells for cancer therapy
High-affinity CD16-polymorphism and Fc-engineered antibodies enable activity of CD16-chimeric antigen receptor-modified T cells for cancer therapy, Published online: 15 November 2018; doi:10.1038/s41416-018-0341-1
High-affinity CD16-polymorphism and Fc-engineered antibodies enable activity of CD16-chimeric antigen receptor-modified T cells for cancer therapy
https://ift.tt/2B8c6RH
Fraud in the field: Signature compliance
EMS providers should be on high alert for fraud and forgery in the patient care report
https://ift.tt/2K5JZFo
Under Pressure, JUUL Withdraws Most Flavored E-Cigs From Market
WEDNESDAY, Nov. 14, 2018 -- JUUL Labs, which commands 70 percent of the U.S. electronic cigarette market, announced yesterday that it would cease selling most flavored versions of its popular vaping pods in retail stores. The announcement comes...
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AMA to Collect Data on Suicide Among Doctors-in-Training
WEDNESDAY, Nov. 14, 2018 -- By collecting data on suicides by medical students, residents, and fellows, the American Medical Association hopes to identify ways to reduce suicides among doctors-in-training. The data collection policy was approved at...
https://ift.tt/2OJhXQA
Red Cross Issues Urgent Call for Blood Ahead of the Holidays
WEDNESDAY, Nov. 14, 2018 -- There is an urgent need for blood and platelet donations in the United States because donations during September and October fell 21,000 units short of hospital needs, the American Red Cross says. "Today, the Red Cross...
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CDC: Record Number of Tickborne Disease Cases in U.S. Last Year
WEDNESDAY, Nov. 14, 2018 -- The number of Americans with tickborne diseases reached a record high of nearly 60,000 in 2017, the U.S. Centers for Disease Control and Prevention says. Most of those cases (42,743) were Lyme disease. There were 36,000...
https://ift.tt/2OHYqQI
AHA: Guidelines Stress Healthy Lifestyle for Lowering Cholesterol
WEDNESDAY, Nov. 14, 2018 -- A healthy lifestyle for lowering cholesterol should be emphasized for reducing cardiovascular risk across the life course, according to a guideline published online Nov. 14 in Circulation to coincide with the annual...
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Mermaid Syndrome: A Case Report of a Rare Congenital Anomaly in Full-Term Neonate with Thumb Deformity
AJP Rep 2018; 08: e328-e331
DOI: 10.1055/s-0038-1669943
The mermaid syndrome (sirenomelia) is an extremely rare anomaly, an incidence of 1 in 100,000 births, in which a newborn born with legs joined together featuring a mermaid-like appearance (head and trunk like humans and tail like fish), and in most cases die shortly after birth. Gastrointestinal and urogenital anomalies and single umbilical artery are clinical outcome of this syndrome. There are two important hypotheses for pathogenesis of mermaid syndrome: vitelline artery steal hypothesis and defective blastogenesis hypothesis. The cause of the mermaid syndrome is unknown, but there are some possible factors such as age younger than 20 years and older than 40 years in mother and exposure of fetus to teratogenics. Here, we introduced 19-year-old mother's first neonate with mermaid syndrome. The mother had gestational diabetes mellitus and neonate was born with single lower limb, ambiguous genitalia, and thumb anomalies, and 4 days after birth, the neonate died due to multiple anomalies and imperforated anus.
[...]
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Abstract | open access Full text
https://ift.tt/2DGz70t
Use of a Fibrin Sealant Patch at Cesarean for Conservative Management of Morbidly Adherent Placenta
AJP Rep 2018; 08: e325-e327
DOI: 10.1055/s-0038-1675848
Background Morbidly adherent placenta represents a surgical challenge and source of maternal morbidity and mortality. We report the use of a fibrin sealant patch to address hemorrhage associated with a morbidly adherent placenta during cesarean delivery. Case A patient underwent repeat cesarean delivery with complete anterior placenta previa and anticipated morbidly adherent placenta. Bleeding persisted following delivery and removal of the placenta, despite uterine artery embolization. A fibrin sealant patch was applied as an adjuvant intervention to the placental bed and hemostasis was achieved without resorting to a hysterectomy. Conclusion Postpartum hemorrhage is an ongoing leading source of maternal morbidity and mortality. A case is presented in which a fibrin sealant patch provided control of focal placental bed bleeding, allowing removal of a focal morbidly adherent placenta and avoidance of hysterectomy.
[...]
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Abstract | open access Full text
https://ift.tt/2RSRZfG
Vascularization, Regeneration and Tissue Engineering
Eur Surg Res 2018;59:229
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Fucoxanthin Exerts Cytoprotective Effects against Hydrogen Peroxide-induced Oxidative Damage in L02 Cells
Several previous studies have demonstrated the excellent antioxidant activity of fucoxanthin against oxidative stress which is closely related to the pathogenesis of liver diseases. The present work was to investigate whether fucoxanthin could protect human hepatic L02 cells against hydrogen peroxide- (H2O2-) induced oxidative damage. Its effects on H2O2-induced cell viability, lactate dehydrogenase (LDH) leakage, intracellular reduced glutathione, and reactive oxygen species (ROS) contents, along with mRNA and protein relative levels of the cytoprotective genes including Nrf2, HO-1, and NQO1, were investigated. The results showed that fucoxanthin could upregulate the mRNA and protein levels of the cytoprotective genes and promote the nuclear translocation of Nrf2, which could be inhibited by the PI3K inhibitor of LY294002. Pretreatment of fucoxanthin resulted in decreased LDH leakage and intracellular ROS content but enhanced intracellular reduced glutathione. Interestingly, pretreatment using fucoxanthin protected against the oxidative damage in a nonconcentration-dependent manner, with fucoxanthin of 5 μM demonstrating the optimal effects. The results suggest that fucoxanthin exerts cytoprotective effects against H2O2-induced oxidative damage in L02 cells, which may be through the PI3K-dependent activation of Nrf2 signaling.
https://ift.tt/2zSE3ec
Effect of Astragalus Polysaccharides on Cardiac Dysfunction in db/db Mice with Respect to Oxidant Stress
Objective. Oxidant stress plays an important role in the development of diabetic cardiomyopathy. Previously we reported that Astragalus polysaccharides (APS) rescued heart dysfunction and cardinal pathological abnormalities in diabetic mice. In the current study, we determined whether the effect of APS on diabetic cardiomyopathy was associated with its impact on oxidant stress. Methods. Db/db diabetic mice were employed and administered with APS. The hematodynamics, cardiac ultra-structure, apoptosis, and ROS formation of myocardium were assessed. The cardiac protein expression of apoptosis target genes (Bax, Bcl-2, and caspase-3) and oxidation target genes (Gpx, SOD2, t/p-JNK, catalase, t/p-p38 MAPK, and t/p-ERK) were evaluated, respectively. Results. APS therapy improved hematodynamics and cardinal ultra-structure with reduced apoptosis and ROS formation in db/db hearts. In addition, APS therapy inhibited the protein expression of apoptosis target genes (Bax, Bcl-2, and caspase-3) and regulated the protein expression of oxidation target genes (enhancing Gpx, SOD2, and catalase, while reducing t/p-JNK, t/p-ERK, and t/p-p38 MAPK) in db/db hearts. Conclusion. Our findings suggest that APS has benefits in diabetic cardiomyopathy, which may be partly associated with its impact on cardiac oxidant stress.
https://ift.tt/2TetECj
Medium-Long-Term Clinical and Radiographic Outcomes of Minimally Invasive Distal Metatarsal Metaphyseal Osteotomy (DMMO) for Central Primary Metatarsalgia: Do Maestro Criteria Have a Predictive Value in the Preoperative Planning for This Percutaneous Technique?
Background. The purpose of this prospective study was first to evaluate the safety and effectiveness of Minimally Invasive Distal Metatarsal Metaphyseal Osteotomy (DMMO) in treating central metatarsalgia, identifying possible contraindications. The second objective was to verify the potential of DMMO to restore a harmonious forefoot morphotype according to Maestro criteria. Methods. A consecutive series of patients with metatarsalgia was consecutively enrolled and treated by DMMO. According to Maestro criteria, preoperative planning was carried out by both clinical and radiological assessment. Patient demographic data, AOFAS scores, 17-FFI, MOXFQ, SF-36, VAS, and complications were recorded. Maestro parameters, relative morphotypes, and bone callus formation were assessed. Statistical analysis was carried out (p
https://ift.tt/2zWBzeH
Exercise inhibits tumor growth and central carbon metabolism in patient-derived xenograft models of colorectal cancer
Abstract
Background
While self-reported exercise is associated with a reduction in the risk of recurrence in colorectal cancer, the molecular mechanisms underpinning this relationship are unknown. Furthermore, the effect of exercise on intratumoral metabolic processes has not been investigated in detail in human cancers. In our current study, we generated six colorectal patient patient-derived xenografts (CRC PDXs) models and treated each PDX to voluntary wheel running (exercise) for 6–8 weeks or no exposure to the wheel (control). A comprehensive metabolomics analysis was then performed on the PDXs to identify exercise induced changes in the tumor that were associated with slower growth.
Results
Tumor growth inhibition was observed in the voluntary wheel running group compared to the control group in three of the six models. A metabolomics analysis first revealed that central carbon metabolism was affected in each model irrespective of treatment. Interestingly, comparison of responsive and resistant models showed that levels of metabolites in nucleotide metabolism, known to be coupled to mitochondrial metabolism, were predictive of response. Furthermore, phosphocreatine levels which are linked to mitochondrial energy demands were associated with inhibition of tumor growth.
Conclusion
Altogether, this study provides evidence that changes to tumor cell mitochondrial metabolism may underlie in part the benefits of exercise.
https://ift.tt/2DF56y4
Recommendations of the International Society of Intraoperative Neurophysiology for intraoperative somatosensory evoked potentials
Somatosensory evoked potentials (SEPs) are an important part of intraoperative neurophysiologic monitoring (IONM) because they provide functional and localizing information about the dorsal somatosensory system and complement motor evoked potentials (MEPs). This document reviews relevant anatomy, physiology, methodology, interpretation and applications and forms recommendations of the International Society of Intraoperative Neurophysiology for intraoperative SEPs. It is also endorsed by the International Federation of Clinical Neurophysiology.
https://ift.tt/2K5sYel
Optimized Deep Neural Network Architecture for Robust Detection of Epileptic Seizures using EEG Signals
Epilepsy is a chronic neurological disorder of the brain that affects people of all ages. Approximately seventy million people worldwide possess epilepsy, making it typically the second most common neurological disease after a migraine (Rogers, 2010). The characterizing feature of epilepsy is repetitive seizures that strike abruptly. Symptoms may run from short suspension of awareness to violent convulsions and once in a while loss of consciousness (Acharya et al., 2013). Electroencephalogram (EEG) is the prime signal that has been widely used for the diagnosis of epilepsy.
https://ift.tt/2B73r1K
Neurophysiological effects of continuous cortical stimulation in epilepsy – spike and spontaneous ECoG activity
Epilepsy constitutes a wide range of brain disorders characterized by a predisposition of developing seizures. Approximately thirty percent of patients with focal epilepsy do not respond adequately to antiepileptic drugs and develop pharmacoresistant epilepsy, sometimes experiencing multiple daily seizures (Abramovici and Bagic 2016), as well as an increased risk of premature death, neurological deficits and reduced quality of life (Chen et al. 2016). Amongst focal drug-resistant epilepsies, surgical resection of the epileptogenic zone provides a good outcome in a majority of cases (West et al.
https://ift.tt/2K3F47W
Single Stage Epilepsy Surgery in Children and Adolescents with Focal Cortical Dysplasia Type II – Prognostic Value of the Intraoperative Electrocorticogram
With up to 80% of well-selected patients becoming seizure-free, epilepsy surgery has proved to be a successful therapeutic option for children and adolescents with drug-resistant epilepsies (Bittar et al., 2002; Dorfer et al., 2013; Gröppel et al., 2015; Jenny et al., 2016). However, seizure freedom after surgery depends on the complete resection/disconnection of the epileptogenic zone (Muthaffar et al., 2017; Rosenow and Luders, 2001). Currently, none of the available diagnostic tests applied during pre-surgical evaluation permit direct measurement of the epileptogenic zone.
https://ift.tt/2B75iDS
Amplitude of Low Frequency Fluctuation (ALFF) study of the spontaneous brain activities of patients with phantom limb pain
OBJECTIVE: Our objective was to use Amplitude of Low-Frequency Fluctuation (ALFF) method to investigate the changes in spontaneous brain activity in HM patients and their relationships with clinical features.
PATIENTS AND METHODS: This study was set out to observe, using Functional magnetic resonance imaging (fMRI), the changes in spontaneous brain activity in patients with phantom limb pain (PLP). Eleven amputees with PLP closely matched in age, sex, and education in a right side lower limb were scanned using fMRI to measure the amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) in the resting state of the brain (GPLP) before use of prosthetic. They were then scanned again after recovering from PLP (GPLPr) after use of artificial limbs. Eleven healthy volunteers (GC) were also scanned.
RESULTS: When compared to GC, GPLP exhibited decreased ALFF in the left inferior parietal lobule, and GPLPr exhibited decreased ALFF in the left precuneus. When compared to GPLP, GC showed positive FC in the part regions of the limbic system structure. When compared to GC, the positive FC in GPLPr was significantly decreased in the midbrain. Finally, when compared to GPLPr, GPLP showed significantly decreased positive FC in the right precuneus and inferior parietal lobe. The central nervous system shows functional changes in the resting state of the brain in patients with PLP, which may indicate the presence of neurobiological changes. The recovery time of the changes may be longer than the pain symptoms of patients.
CONCLUSIONS: The technique of fMRI of the resting network of the brain in patients with PLP may be able to be used to monitor clinical therapeutic effects.
L'articolo Amplitude of Low Frequency Fluctuation (ALFF) study of the spontaneous brain activities of patients with phantom limb pain sembra essere il primo su European Review.
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Prevalence of Metastasis and Survival of 788 patients with T1 Rectal Carcinoid Tumors
Prevalence of rectal carcinoids is increasing, partly due to increased colorectal cancer screening. Local excision (endoscopic or trans-anal excision) is usually performed for small (<1-2 cm) rectal carcinoids but data on clinical outcomes from large population-based U.S. studies are lacking. The aims of this study were to determine the prevalence of metastasis of resected small rectal carcinoid tumors using a large national cancer database and to evaluate the long-term survival of patients after local resection as compared with radical surgery.
https://ift.tt/2DpOdpU
The incremental value of DNA analysis in pancreatic cysts stratified by clinical risk factors
We determined the incremental predictive value of pancreatic cyst fluid molecular analysis to assessing malignancy risk over long term follow-up of a well-characterized cohort, given the underlying predictive value of imaging parameters routinely used to triage such patients.
https://ift.tt/2PZlQFZ
Intestinal metaplasia of the gastric cardia: findings in patients with versus without Barrett’s esophagus
There is controversy about finding intestinal metaplasia (IM) of the gastric cardia on biopsy. The most recent American GI society guideline comments that IM cardia is not more common in patients with Barrett's. It provides limited guidance on whether the cardia should be treated when patients with Barrett's undergo endoscopic eradication therapy (EET) and whether the cardia should be biopsied after ablation. The aims of our study were to determine the frequency in the proximal stomach of (1) histologic gastric cardia mucosa and (2) IM cardia.
https://ift.tt/2PWW8ll
Activated sludge bacterial communities of typical wastewater treatment plants: distinct genera identification and metabolic potential differential analysis
To investigate the differences in activated sludge microbial communities of different wastewater treatment plants (WWTPs) and understand their metabolic potentials, we sampled sludge from every biological trea...
https://ift.tt/2qON2cl
Correction to: Autolysis of Pichia pastoris induced by cold
The original version of this article (Bartolo-Aguilar et al. 2017) was written and published including the first construction strategy of pLGC09, but not the final one. This error was pointed out by a reader a...
https://ift.tt/2FmIlAq
Can a Charged Surfactant Unfold an Uncharged Protein?
Does sodium dodecyl sulfate (SDS) denature proteins through electrostatic SDS-protein interactions? We show that a protein completely lacking charged side chains is unfolded by SDS in a manner similar to charged proteins, revealing that formal protein charges are not required for SDS-induced protein unfolding or binding.
https://ift.tt/2qOa7vQ
Attitudes, Beliefs, and Practices of Pediatric Palliative Care Physicians Regarding the Use of Methadone in Children with Advanced Cancer
Methadone is a long-acting opioid known for its unique pharmacokinetic and pharmacodynamic properties. Most research on methadone in children is limited to its effect on the prolongation of the corrected QT (QTc) interval.
https://ift.tt/2zcq0R6
Factors Predisposing Terminally Ill Cancer Patients’ Preferences for Distinct Patterns/States of Life-Sustaining Treatments over Their Last Six Months
High-quality EOL care depends on thoroughly assessing terminally ill patients' preferences for end-of-life (EOL) care and tailoring care to individual needs. Studies on predictors of EOL-care preferences were primarily cross-sectional and assessed preferences for multiple life-sustaining treatments (LSTs), making clinical applications difficult.
https://ift.tt/2OOKHI4
Destination Therapy: Standardizing The Role of Palliative Medicine & Delineating The Dt-Lvad Journey
Destination therapy (DT) patients face significant challenges as they transition from chronic LVAD support to comfort-oriented care . Integration of Palliative Medicine (PM) into the multidisciplinary team is important to facilitate advanced care planning and improve quality of life (QoL).
https://ift.tt/2z95aSy
Prevalence and characteristics of patients being at risk of deteriorating and dying in primary care
Understanding the prevalence and characteristics of primary care outpatients being at risk of deteriorating and dying may allow general practitioners (GPs) to identify them, and initiate end-of-life discussions.
https://ift.tt/2OJnEhK
A brief measure for the assessment of competence in coping with death: The Coping with Death Scale short version
The coping with death competence is of great importance for palliative care professionals, who face daily exposure to death. It can keep them from suffering compassion fatigue and burnout, thus enhancing the quality of the care provided. Despite its relevance, there are only two measures of professionals' ability to cope with death. Specifically, the Coping with Death Scale (CDS) has repeatedly shown psychometric problems with some of its items.
https://ift.tt/2z99OQG
‘Just as I expected’: A longitudinal cohort study of the impact of response expectancies on side effect experiences during radiotherapy for prostate cancer
Previous research has indicated pre-treatment response expectancies of side effects often predict subsequent toxicity severity. However, this has been largely based on female patients undergoing chemotherapy.
https://ift.tt/2OK45Wy
Physiological Effect of Prone Position in Children with Severe Bronchiolitis: A Randomized Cross-Over Study (BRONCHIO-DV)
To assess the effect of the prone position on physiological measures, including inspiratory effort, metabolic cost of breathing, and neural drive to the diaphragm as compared with the supine position in infants with severe bronchiolitis requiring noninvasive ventilation.
https://ift.tt/2K1UJ7E
Influence of Fathers' Early Parenting on the Development of Children Born Very Preterm and Full Term
To examine factors associated with fathers' early parenting behaviors (including very preterm [VPT] birth, familial social risk, child sex, and child medical risk), and the relationship between fathers' early parenting behaviors and later child development.
https://ift.tt/2B7p5D8
Increase of CaV3 channel activity induced by HVA β1b-subunit is not mediated by a physical interaction
Low voltage-activated (LVA) calcium channels are crucial for regulating oscillatory behavior in several types of neurons and other excitable cells. LVA channels dysfunction has been implicated in epilepsy, neu...
https://ift.tt/2PptlX8
Highly clarithromycin-resistant Helicobacter pylori infection in asymptomatic children from a rural community of Cajamarca-Peru
The objective of this study was to determine the prevalence of clarithromycin-resistant Helicobacter pylori in asymptomatic children in a rural community of Cajamarca (northern Peru).
https://ift.tt/2QJuuFy
Sexuality, sexually transmitted infections and contraception among health sciences students in university of Lomé, Togo
Evaluate the practice of sexuality, contraception and the risk of sexually transmitted infections among students in the Faculty of Health Sciences, University of Lomé, Togo.
https://ift.tt/2Ptrpgn
Adenosine and adenosine-5′-monophosphate ingestion ameliorates abnormal glucose metabolism in mice fed a high-fat diet
We have previously reported that ingestion of adenosine (ADN) and adenosine-5′-monophosphate (AMP) improves abnormal glucose metabolism in the stroke-prone spontaneously hypertensive rat model of non-obesity-a...
https://ift.tt/2FnjPPS
Croton gratissimus leaf extracts inhibit cancer cell growth by inducing caspase 3/7 activation with additional anti-inflammatory and antioxidant activities
Croton species (Euphorbiaceae) are distributed in different parts of the world, and are used in traditional medicine to treat various ailments including cancer, inflammation, parasitic infections and oxidative st...
https://ift.tt/2qNJ5V8
Front Cover
The cover image is based on the Original Article Genomic screening in rare disorders: New mutations and phenotypes, highlighting ALG14 as a novel cause of severe intellectual disability, by Malin Kvarnung et al., https://doi.org/10.1111/cge.13448.
The cover image is based on the Original Article Genomic screening in rare disorders: New mutations and phenotypes, highlighting ALG14 as a novel cause of severe intellectual disability, by Malin Kvarnung et al., https://doi.org/10.1111/cge.13448.
https://ift.tt/2DFALzo
Age-Related Characteristics and Outcomes for Patients With Severe Trauma: Analysis of Japan’s Nationwide Trauma Registry
Although geriatric trauma patients are becoming more common, few large-scale analyses have comprehensively evaluated geriatric-specific characteristics in trauma. This study aims to clarify the age-specific characteristics, outcomes, and predictive accuracy of current trauma scoring systems among geriatric trauma patients.
https://ift.tt/2RXh9Kh
A Cost-Effectiveness Analysis Comparing Clinical Decision Rules PECARN, CATCH, and CHALICE With Usual Care for the Management of Pediatric Head Injury
To determine the cost-effectiveness of 3 clinical decision rules in comparison to Australian and New Zealand usual care: the Children's Head Injury Algorithm for the Prediction of Important Clinical Events (CHALICE), the Pediatric Emergency Care Applied Research Network (PECARN), and the Canadian Assessment of Tomography for Childhood Head Injury (CATCH).
https://ift.tt/2DIpSwG
It’s Time to Wake Up to the Use of Pharmacologic Sleep Aids by Emergency Physicians
SEE RELATED ARTICLE, P. ■■■.
https://ift.tt/2RUpqyh
Older Blood Is Associated With Increased Mortality and Adverse Events in Massively Transfused Trauma Patients: Secondary Analysis of the PROPPR Trial
The transfusion of older packed RBCs may be harmful in critically ill patients. We seek to determine the association between packed RBC age and mortality among trauma patients requiring massive packed RBC transfusion.
https://ift.tt/2DGiC4x
Oral Ondansetron to Reduce Intravenous Fluid Rehydration: Context Matters
SEE RELATED ARTICLE, P. ■■■.
https://ift.tt/2RVdiwX
Biphasic Modulation of NMDA Receptor Function by Metabotropic Glutamate Receptors
A recently reported rapid potentiation of NMDA receptors by Group I metabotropic glutamate receptors (mGluRIs) via a Homer protein link is distinct from the classical, relatively slow inhibitory G-protein-associated signaling triggered by mGluRI activation. The relationship between these two mechanisms remains unknown. Here, we focused on the mGluRI-dependent modulation of NMDAR response in hippocampal dentate gyrus granule cells and cerebellar granule cells of C57BL6-J mice and found that these two contrasting mechanisms overlap competitively on the time scale from hundreds of milliseconds to seconds, with the net effect depending on the cell type. At a shorter time interval (units of millisecond), the Homer-mediated signal from mGluRIs prevails, causing upregulation of NMDAR function, in both dentate gyrus granule cells and cerebellar granule cells. Our results shed light on the possible mechanisms of anti-schizophrenia drugs that disrupt Homer-containing protein link.
SIGNIFICANCE STATEMENT Here we study modulation of NMDA receptors triggered by activation of metabotropic glutamate receptors Group I via two distinct pathways: classical G-protein signaling system and newly discovered high-speed modulatory mechanism associated with Homer-protein-containing direct molecular link. We found that these two contrasting mechanisms overlap competitively on the time scale from hundreds of milliseconds to seconds, with the net effect depending on the cell type. We have also found that both crosstalk mechanisms cause significant changes in synaptic strength and plasticity. Our results resolve an apparent discrepancy between earlier studies that demonstrated contradictive effects of Homer-containing protein link disruption on NMDA receptor signaling. On top of that, our data provide a plausible explanation for unclear action mechanisms of anti-schizophrenia drugs.
https://ift.tt/2PvMXJp
A Pool of Postnatally Generated Interneurons Persists in an Immature Stage in the Olfactory Bulb
Calretinin (CR)-expressing periglomerular (PG) cells are the most abundant interneurons in the glomerular layer of the olfactory bulb. They are predominately generated postnatally from the septal and dorsal subventricular zones that continue producing them well into adulthood. Yet, little is known about their properties and functions. Using transgenic approaches and patch-clamp recording in mice of both sexes we show that CR(+) PG cells of both septal and dorsal origin have homogeneous morphological and electrophysiological properties. However, unlike other PG cells, these axonless neurons express a surprisingly small repertoire of voltage-activated channels and do not fire or fire at most a single and often small action potential. Moreover, they are not innervated by olfactory sensory neurons and receive little synaptic inputs from mitral or tufted cells at excitatory synapses where NMDA receptors predominate. These membrane and synaptic properties, that resemble those of newborn immature neurons not yet integrated in the network, persist over time and limit the recruitment of CR(+) PG cells by afferent inputs that strongly drive local network activity. Together, our results show that postnatally generated CR(+) PG cells continuously supply a large pool of neurons with unconventional properties. These data also question the contribution of CR(+) PG cells in olfactory bulb computation.
SIGNIFICANCE STATEMENT Calretinin-expressing PG cells are by far the most abundant interneurons in the glomerular layer of the olfactory bulb. They are continuously produced during postnatal life, including adulthood, from neural stem cells located in the subventricular zones. Surprisingly, unlike other postnatally generated newborn neurons that quickly integrate into preexisting olfactory bulb networks, calretinin-expressing PG cells retain immature properties that limit their recruitment in local network activity for weeks, if not months, as if they would never fully mature. The function of this so far unsuspected pool of latent neurons is still unknown.
https://ift.tt/2K7Ai9G
Inhibitory Signaling to Ion Channels in Hippocampal Neurons Is Differentially Regulated by Alternative Macromolecular Complexes of RGS7
The neuromodulatory effects of GABA on pyramidal neurons are mediated by GABAB receptors (GABABRs) that signal via a conserved G-protein-coupled pathway. Two prominent effectors regulated by GABABRs include G-protein inwardly rectifying K+ (GIRK) and P/Q/N type voltage-gated Ca2+ (CaV2) ion channels that control excitability and synaptic output of these neurons, respectively. Regulator of G-protein signaling 7 (RGS7) has been shown to control GABAB effects, yet the specificity of its impacts on effector channels and underlying molecular mechanisms is poorly understood. In this study, we show that hippocampal RGS7 forms two distinct complexes with alternative subunit configuration bound to either membrane protein R7BP (RGS7 binding protein) or orphan receptor GPR158. Quantitative biochemical experiments show that both complexes account for targeting nearly the entire pool of RGS7 to the plasma membrane. We analyzed the effect of genetic elimination in mice of both sexes and overexpression of various components of RGS7 complex by patch-clamp electrophysiology in cultured neurons and brain slices. We report that RGS7 prominently regulates GABABR signaling to CaV2, in addition to its known involvement in modulating GIRK. Strikingly, only complexes containing R7BP, but not GPR158, accelerated the kinetics of both GIRK and CaV2 modulation by GABABRs. In contrast, GPR158 overexpression exerted the opposite effect and inhibited RGS7-assisted temporal modulation of GIRK and CaV2 by GABA. Collectively, our data reveal mechanisms by which distinctly composed macromolecular complexes modulate the activity of key ion channels that mediate the inhibitory effects of GABA on hippocampal CA1 pyramidal neurons.
SIGNIFICANCE STATEMENT This study identifies the contributions of distinct macromolecular complexes containing a major G-protein regulator to controlling key ion channel function in hippocampal neurons with implications for understanding molecular mechanisms underlying synaptic plasticity, learning, and memory.
https://ift.tt/2B5iBnY
CRISPR-mediated Genome Editing of the Human Fungal Pathogen Candida albicans
Efficient genome engineering of Candida albicans is critical to understanding the pathogenesis and development of therapeutics. Here, we described a protocol to quickly and accurately edit the C. albicans genome using CRISPR. The protocol allows investigators to introduce a wide variety of genetic modifications including point mutations, insertions, and deletions.
https://ift.tt/2zbAMXY
Novel Methods for Intranasal Administration Under Inhalation Anesthesia to Evaluate Nose-to-Brain Drug Delivery
Here, we describe two novel methods of stable intranasal administration under inhalation anesthesia with minimal physical stress for experimental animals. We also describe a method for quantitative evaluation of drug distribution levels in the brain via the nose-to-brain pathway using radiolabeled [14C]-inulin as a model substrate of water-soluble macromolecules.
https://ift.tt/2OK0rvL
Enhancement Method of Surface Acoustic Wave-Atomizer Efficiency for Olfactory Display
We establish here a method for coating the surface of a surface acoustic wave (SAW) device with amorphous Teflon film to improve the atomization efficiency required for application to an olfactory display.
https://ift.tt/2zcgmxS
Assessing Cellular Stress and Inflammation in Discrete Oxytocin-secreting Brain Nuclei in the Neonatal Rat Before and After First Colostrum Feeding
https://ift.tt/2OK0rff
Using a Classroom-Based Deese Roediger McDermott Paradigm to Assess the Effects of Imagery on False Memories
The method presented here induced false memories using lists of related words and also assessed the effects of imagery instructions on the recall and recognition of those false memories. This protocol details a modified version of the Deese Roediger McDermott (DRM) paradigm.
https://ift.tt/2z8ZvvM
Gaze in Action: Head-mounted Eye Tracking of Children's Dynamic Visual Attention During Naturalistic Behavior
Young children do not passively observe the world, but rather actively explore and engage with their environment. This protocol provides guiding principles and practical recommendations for using head-mounted eye trackers to record infants' and toddlers' dynamic visual environments and visual attention in the context of natural behavior.
https://ift.tt/2OHHCt6
Pathological characteristics and genetic features of melanin-producing medullary thyroid carcinoma
To study the clinicopathological characteristics and genetic features of melanin-producing medullary thyroid carcinoma (MP-MTC).
https://ift.tt/2zacsFL
Inhibition of Calcium/Calmodulin‐Dependent Protein Kinase Kinase (CaMKK) Exacerbates Impairment of Endothelial Cell and Blood‐Brain Barrier after Stroke
Abstract
Brain microvascular endothelial cells play an essential role in maintaining blood‐brain barrier (BBB) integrity, and disruption of the BBB aggravates the ischemic injury. CaMKK (α and β) is a major kinase activated by elevated intracellular calcium. Previously, we demonstrated that inhibition of CaMKK exacerbated outcomes, conversely, overexpression reduced brain injury after stroke in mice. Interestingly, CaMKK has been shown to activate a key endothelial protector, Sirtuin 1 (SIRT1). We hypothesized that CaMKK protects brain endothelial cells via SIRT1 activation after stroke. In this study, Oxygen‐Glucose Deprivation (OGD) was performed in human brain microvascular endothelial cells. Stroke was induced by middle cerebral artery occlusion (MCAO) in male mice. Knockdown of CaMKK β using siRNA increased cell death following OGD. Inhibition of CaMKK β by STO‐609 significantly and selectively down‐regulated levels of phosphorylated SIRT1 after OGD. Changes in the downstream targets of SIRT1 were observed following STO‐609 treatment. The effect of STO‐609 on cell viability after OGD was absent when SIRT1 was concurrently inhibited. We also demonstrated that STO‐609 increased endothelial expression of the pro‐inflammatory proteins ICAM‐1 and VCAM‐1 and inhibition of CaMKK exacerbated OGD‐induced leukocyte‐endothelial adhesion. Finally, intracerebroventricular injection of STO‐609 exacerbated endothelial apoptosis and reduced BBB integrity after 24‐hour reperfusion following MCAO in vivo. Collectively, these results demonstrated that CaMKK inhibition reduced endothelial cell viability, exacerbated inflammatory responses and aggravated BBB impairment after ischemia. CaMKK activation may attenuate ischemic brain injury via protection of the microvascular system and a reduction in the infiltration of pro‐inflammatory factors.
This article is protected by copyright. All rights reserved.
https://ift.tt/2K6Iu9O
Analysis of sero-epidemiological characteristics of varicella in healthy children in Jiangsu Province, China
In recent years, outbreaks of varicella have continued to occur, and the coverage rate of varicella vaccine in Jiangsu Province, China, remains unclear. This study aims to analyse the levels of immune antibody...
https://ift.tt/2B7htR4
Chronic hepatitis B genotype E in African migrants: response to nucleos(t)ide treatment in real clinical practice
Hepatitis B virus (HBV) genotype E is a poorly studied genotype that almost exclusively occurs in African people. It seems to harbour intrinsic potential oncogenic activity and virological characteristics of i...
https://ift.tt/2K2KLCX
Field suitability and diagnostic accuracy of the Biocentric® open real-time PCR platform for plasma-based HIV viral load quantification in Swaziland
Viral load (VL) testing is being scaled up in resource-limited settings. However, not all commercially available VL testing methods have been evaluated under field conditions. This study is one of a few to eva...
https://ift.tt/2B5bo7A
Seroprevalence and distribution of leptospirosis serovars among wet market workers in northeastern, Malaysia: a cross sectional study
Leptospirosis is a zoonotic disease associated with occupations which exposed workers to environments contaminated with urine of infected animals. The objective of this study was to determine the seroprevalenc...
https://ift.tt/2K5lXuf
Genetic diversity of drug resistant Mycobacterium Tuberculosis in local area of Southwest China: a retrospective study
By 2014 although tuberculosis (TB) incidence had fallen by an average of 1.5% per year since 2000 and was 18% lower than the level of in 2000, 1.5 million people died for TB in that year. One of reason was tha...
https://ift.tt/2B5uzxW
Implanted Pumps: Safety Communication - Use Caution When Selecting Pain Medicine for Intrathecal Administration
[Posted 11/14/2018] AUDIENCE: Patient, Caregiver, Health Professional, Pain Management, Pharmacy, Neurology, Surgery ISSUE: The FDA is aware that patients undergoing treatment or management of pain are commonly given pain medicines in the spinal...
https://ift.tt/2QI75Vb
A Droplet-Based Microfluidic Approach and Microsphere-PCR Amplification for Single-Stranded DNA Amplicons
https://ift.tt/2RWpyO0
CRISPR-Cas9-based Genome Engineering to Generate Jurkat Reporter Models for HIV-1 Infection with Selected Proviral Integration Sites
https://ift.tt/2DExWyj
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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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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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