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Otolaryngology (ENT) Sub-Specialties
News-Medical.net ... and various sub-specialties. These include such disciplines as pediatrics, oncology, sinus disease, and surgery. Because of their range of capabilities, ENT surgeons might one day correct a child's tonsillitis and on the next day treat an adult's ... and more » |
Pro Football Hall of Famer and Cancer Survivor Jim Kelly Teams Up with Merck and Leading Cancer Organizations to ...
Yahoo Finance Head and neck cancer describes a number of different tumors that develop in or around the throat, larynx, nose, sinuses and mouth. Each year more than 60,000 new cases of head and neck cancer are diagnosed in the U.S. Many people with head and neck ... and more » |
Long non-coding RNAs (lncRNAs) are dysregulated in many cancer types, which are believed to play crucial roles in regulating several hallmarks of cancer biology. Triple Negative Breast Cancer (TNBC) is a very aggressive subtype of normal breast cancer, which has features of negativity for ER, PR and HER2. Great efforts have been made to identify an association between lncRNAs expression profiles and TNBC, and to understand the functional role and molecular mechanism on aberrant-expressed lncRNAs. In this review, we summarized the existed knowledge on the systematics, biology, and function of lncRNAs. The advances from the most recent studies of lncRNAs in the predicament of breast cancer, TNBC, are highlighted, especially the functions of specifically selected lncRNAs. We also discussed the potential value of these lncRNAs in TNBC, providing clues for the diagnosis and treatments of TNBC. This article is protected by copyright. All rights reserved
Diabetes mellitus (DM) induces bone deterioration, while mechanical stimulation promotes osteocyte-driven bone formation. We aimed to evaluate the interaction of acute exposure (24h) to high glucose (HG) with both the pro-survival effect conferred to osteocytic MLO-Y4 cells and osteoblastic MC3T3-E1 cells by mechanical stimulation and the interaction of these cells with osteoclast precursor RAW264.7 cells. We found that 24h of HG (25 mM) pre-exposure prevented both cell survival and ERK and β-catenin nuclear translocation upon mechanical stimulation by fluid flow (FF) (10 min) in both MLO-Y4 and MC3T3-E1 cells. However, migration of RAW 264.7 cells was inhibited by MLO-Y4 cell-conditioned medium (CM), but not by MC3T3-E1 cell-CM, with HG or FF. This inhibitory effect was associated with consistent changes in VEGF, RANTES, MIP-1α, MIP-1β MCP-1 and GM-CSF in MLO-Y4 cell-CM. RAW264.7 proliferation was inhibited by MLO-Y4 CM under static or HG conditions, but itincreased by FF-CM with or without HG. In addition, both FF and HG abrogated the capacity of RAW 264.7 cells to differentiate into osteoclasts, but in a different manner. Thus, HG-CM in static condition allowed formation of osteoclast-like cells, which were unable to resorb hydroxyapatite. In contrast, FF-CM prevented osteoclastogenesis even in HG condition. Moreover, HG did not affect basal RANKL or IL-6 secretion or their inhibition induced by FF in MLO-Y4 cells. In conclusion, this in vitro study demonstrates that HG exerts disparate effects on osteocyte mechanotransduction, and provides a novel mechanism by which DM disturbs skeletal metabolism through altered osteocyte-osteoclast communication. This article is protected by copyright. All rights reserved
In this study, the gelation and thermal characteristics of microwave extracted fish scale gelatin blended with natural gums such as gum arabic (AG), xanthan gum (XG), guar gum (GG), and tragacanth gum (TG) was evaluated. The nature of interaction and behavior of gelatin in presence of various gums was confirmed by particle size analysis, viscosity profile, FT-IR analysis and turbidity measurements. DSC data revealed that addition of AG, TG and GG remarkably improved the thermal stability of fish gelatin gel. The composite gels of TG, AG, and XG exhibited higher hardness and bloom strength values as compared to pure fish gelatin implying its textural synergy. Based on qualitative descriptive analysis, TG was found to be superior in improving the stability of fish gelatin gel, closely followed by AG. The results suggest that addition of these gums can reduce syneresis and retard melting of gelatin gels at ambient temperature, which are otherwise soft and thermally unstable.
Silver nanoparticles (Ag-NPs) were synthesized using banana powder as a reducing and stabilizing agent, and banana/Ag-NPs composite films with different concentration of Ag-NPs were prepared simultaneously. The composite films were yellowish brown and exhibited characteristic plasmon resonance peak of Ag-NPs at 430 nm. The optical, mechanical, water vapor barrier, thermal stability, and antimicrobial properties of the composite films were greatly influenced by the concentration of Ag-NPs. The composite film with a silver concentration of 1.0 mM demonstrated the highest tensile strength, thermal stability, transparency, and water contact angle with the lowest water vapor permeability (1.36 ± 0.10 × 10−9 g m/m2 Pa s). Also, the composite films incorporated with 1.0 mM of Ag-NPs exhibited a strong antibacterial activity against both Gram-positive (Listeria monocytogenes) and Gram-negative (Escherichia coli) food-borne pathogenic bacteria.
The study optimized the hydrolysis conditions for the production of fish collagen peptides from skin of Malabar grouper (Epinephelus malabaricus) using response surface methodology. The hydrolysis was done with enzymes pepsin, papain and protease from bovine pancreas. Effects of process parameters viz: pH, temperature, enzyme substrate ratio and hydrolysis time of the three different enzymes on degree of hydrolysis were investigated. The optimum response of degree of hydrolysis was estimated to be 10, 20 and 28% respectively for pepsin, papain and protease. The functional properties of the product developed were analysed which showed changes in the properties from proteins to peptides. SDS-PAGE combined with MALDI TOF method was successfully applied to determine the molecular weight distribution of the hydrolysate. The electrophoretic pattern indicated that the molecular weights of peptides formed due to hydrolysis were nearly 2 kDa. MALDI TOF spectral analysis showed the developed hydrolysate contains peptides having molecular weight in the range below 2 kDa.
Currently, there is a growing interest in the use of non-Saccharomyces yeast to enhance the aromatic quality of wine, with pure or mixed cultures, as well as sequential inoculation. Volatile components of wines were closely related to their sensory quality. Hence, to study the evolution of volatile compounds during fermentation was of great interest. For this, sampling methods that did not alter the volume of fermentation media were the most suitable. This work reports the usefulness of headspace sorptive extraction as non-invasive method to monitor the changes in volatile compounds during fermentation. This method allowed monitoring of 141 compounds throughout the process of fermentation by Saccharomyces cerevisiae and Lachancea thermotolerans strains. Both strains showed a similar ability to ferment a must with high sugar content. The S. cerevisiae strain produced higher amount of volatile compounds especially esters that constitutes fruity aroma than L. thermotorelans.
The effect of postharvest chitosan, gallic acid (GA) and chitosan gallate (CG) dipping treatments at different concentrations on quality parameters, antioxidant compounds, free radical scavenging capacity (FRSC) and enzymes activities of ‘Sukkari’ bananas were studied during storage (ripening) at 20 ± 2 °C and 60–70% RH for 13 days. Weight loss and peel color index (the change from green to yellow) increased while, membrane stability index of peel tissues, pulp firmness and acidity decreased during storage. CG and GA treatments slowed down the changes in these parameters compared to control. Total soluble solids (TSS) concentration increased during storage and was lower at CG than other treatments. TSS/acid ratio increased during storage and showed higher value after storage than initial. This ratio was lower at 1% chitosan, 0.075% GA and CG treatments than control. Both vitamin C and total flavonoids concentrations decreased during storage and were not affected by the applied treatments. Total phenols concentration decreased during storage and was higher at acetic acid and the high rate of chitosan, GA and CG treatments than control. FRSC (DPPH IC50 values) of fruit peel ranged from 2.54 to 4.19 µg phenolics concentration among the treatments. FRSC was not affected by the applied treatments but increased (lower IC50 value) during shelf life. The possible relations of these biochemical changes with the activities of the enzymes α-amylase, xylanase, polygalacturonase, peroxidase and polyphenoloxidase were discussed. It is concluded that postharvest CG and GA treatments delayed ripening and maintained better quality parameters of ‘Sukkari’ bananas during 13 days of shelf life than control.
In this study vacuum impregnation (VI) was employed for the iron enrichment of olive fruits, which are very interesting as food vehicle for VI mineral supplementation for the porosity of their pulp. NaFeEDTA was chosen for olives fortification since it prevents iron from binding with compounds that could hinder it from being efficiently absorbed and since it causes few organoleptic problems. In order to improve the efficiency of the VI process, several parameters of the whole process were studied by design of experiment techniques. First of all D-optimal design was employed for a preliminary screening of the most significant process variables and showed that the concentration of VI solution was by far the most significant process variable, though its time in contact with olives was also significant. A factorial design was then applied to the remaining variables and it showed that the speed of the addition of VI solution was also significant. Finally, the application of a face centered composite design to the three selected variables allowed to detect processing conditions leading to final iron contents of 1.5–3 mg/g, corresponding to an introduction of 10–15 mg Fe with four or five fortified olive fruits. No effect on olive taste was observed at these concentrations. The results showed that olive fruits were the most interesting vehicles for the supplementation of both iron and other minerals.
Although a lot of work has been conducted in the pesticide residues analysis in food matrices but the quality determination (with respect to major contaminants such as pesticide residues) in medicinal plant matrices has a long way to go. Hence a study was conducted to determine pesticide residues in four medicinal herbs, which are highly traded commodities in international market. Samples were extracted and cleaned up by modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) approach and analyzed by gas chromatograph–mass spectrometer (GC–MS). The method was subjected to thorough validation procedure in-terms of accuracy, precision, limits of quantification (LOQ), matrix effect, linearity and uncertainty analysis. The mean recoveries for most of the pesticides were in the range of 70–120% with RSD <20% and measurement uncertainties were less than 20% for all the compounds at spiking level of 0.5 mg kg−1 in all the matrices. The limits of quantification (LOQ) ranged from 0.01 to 0.069 mg kg−1. The proposed method was successfully applied to determine pesticide residues in 52 commercial market samples obtained from different locations in India.
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HPV vaccine vital for cervical health
Pueblo Chieftain According to the Centers for Disease Control and Prevention, in 2008-2012 there were 38,793 HPV-associated cancers in the United States; 15,793 cases were in men (cancer at the back of the throat and tongue) and 23,000 cases in women (cervical cancer ... and more » |
HPV vaccine now funded for boys
Scoop.co.nz “Most countries who have to date introduced HPV vaccine have focused on the cervical cancer strategy as this is the biggest killer and when resources are constrained – i.e. particularly in low- and middle-income countries – the cost-benefit lines up ... and more » |
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Otolaryngology (ENT) Sub-Specialties
News-Medical.net ... and various sub-specialties. These include such disciplines as pediatrics, oncology, sinus disease, and surgery. Because of their range of capabilities, ENT surgeons might one day correct a child's tonsillitis and on the next day treat an adult's ... and more » |
18F-fluorethyltyrosine-(FET)-PET and MRI-based relative cerebral blood volume (rCBV) have both been used to characterize gliomas. Recently, inter-individual correlations between peak static FET-uptake and rCBV have been reported. Herein, we assess the local intra-lesional relation between FET-PET parameters and rCBV.
Thirty untreated glioma patients (27 high-grade) underwent simultaneous PET/MRI on a 3 T hybrid scanner obtaining structural and dynamic susceptibility contrast sequences. Static FET-uptake and dynamic FET-slope were correlated with rCBV within tumour hotspots across patients and intra-lesionally using a mixed-effects model to account for inter-individual variation. Furthermore, maximal congruency of tumour volumes defined by FET-uptake and rCBV was determined.
While the inter-individual relationship between peak static FET-uptake and rCBV could be confirmed, our intra-lesional, voxel-wise analysis revealed significant positive correlations (median r = 0.374, p < 0.0001). Similarly, significant inter- and intra-individual correlations were observed between FET-slope and rCBV. However, rCBV explained only 12% of the static and 5% of the dynamic FET-PET variance and maximal overlap of respective tumour volumes was 37% on average.
Our results show that the relation between peak values of MR-based rCBV and static FET-uptake can also be observed intra-individually on a voxel basis and also applies to a dynamic FET parameter, possibly determining hotspots of higher biological malignancy. However, just a small part of the FET-PET signal variance is explained by rCBV and tumour volumes determined by the two modalities showed only moderate overlap. These findings indicate that FET-PET and MR-based rCBV provide both congruent and complimentary information on glioma biology.
The Taylor Spatial Frame (TSF) is used to correct orthopedic conditions such as correction osteotomies in delayed fracture healing and pseudarthrosis. Long-term TSF-treatments are common and may lead to complications. Current conventional radiological methods are often unsatisfactory for therapy monitoring. Hence, an imaging technique capable of quantifying bone healing progression would be advantageous.
A cohort of 24 patients with different orthopedic conditions, pseudarthrosis (n = 10), deformities subjected to correction osteotomy (n = 9), and fracture (n = 5) underwent dynamic [18F]-fluoride (Na18F) PET/CT at 8 weeks and 4 months, respectively, after application of a TSF. Parametric images, corresponding to the net transport rate of [18F]-fluoride from plasma to bone, K i were calculated. The ratio of the maximum K i at PET scan 2 and 1 ( \( {\overline{K}}_{i, \max } \) ) as well as the ratio of the maximum Standard Uptake Value at PET scan 2 and 1 ( \( {\overline{SUV}}_{\max } \) ) were calculated for each individual. Different treatment end-points were scored, and the overall treatment outcome score was compared with the osteoblastic activity progression as scored with \( {\overline{K}}_{i, \max } \) or \( {\overline{SUV}}_{\max } \) .
\( {\overline{K}}_{i, \max } \) and \( {\overline{SUV}}_{\max } \) were not correlated within each orthopedic group (p > 0.1 for all groups), nor for the pooled population (p = 0.12). The distribution of \( {\overline{K}}_{i, \max } \) was found significantly different among the different orthopedic groups (p = 0.0046) -also for \( {\overline{SUV}}_{\max } \) (p = 0.022). The positive and negative treatment predictive values for \( {\overline{K}}_{i, \max } \) were 66.7 % and 77.8 %, respectively. Corresponding values for \( {\overline{SUV}}_{\max } \) were 25 % and 33.3 %
The \( {\overline{K}}_{i, \max } \) obtained from dynamic [18F]-fluoride-PET imaging is a promising predictive factor to evaluate changes in bone healing in response to TSF treatment.
Increased articular 99mTc MDP uptake on blood pool imaging (BPI) of patients with rheumatologic conditions is indicative of active inflammatory changes, and has been suggested as a strong predictor of response to radiosynoviorthesis (RSO). In this study, we aimed to assess the value of pretreatment BPI positivity (i.e. scintigraphic-apparent hyperemia) for successful RSO in hemophilic arthropathy.
Thirty-four male patients with painful hemophilic arthropathy underwent RSO after failure of conservative treatment. Treated joints comprised the knee in eight, elbow in five, and ankle in 21 patients. Pretreatment triple-phase bone scintigraphy showed hyperemic joints (pathologic BPI) in 17 patients, whereas 17 patients had no increased tracer uptake on BPI. Response to RSO was evaluated 6 months post-treatment by measuring changes in intensity of arthralgia according to the visual analog scale (VAS), bleeding frequency, and range of motion. The association between hyperemia (pathologic BPI) and treatment outcome was examined using nonparametric tests for independent samples.
Clinically evident pain relief occurred in 26 patients (76.5 %), and the mean VAS decreased from 7.7 ± 1.1 to 4.6 ± 2.7 (p < 0.001). Joint bleeding frequency (hemarthrosis) decreased from 4.5 ± 0.6 to 2.1 ± 0.4 during the first 6 months after RSO (p < 0.001). For both parameters (pain relief and bleeding frequency), patients experienced a similar benefit from RSO regardless of pretreatment BPI: arthralgia (p = 0.312) and frequency of hemarthrosis (p = 0.396). No significant improvement was observed for range of motion, but it was significantly more restricted in hyperemic joints both before (p = 0.036) and after treatment (p = 0.022).
Hemophilic arthropathy can be effectively treated with RSO regardless of pre-therapeutic BPI. Patients in whom articular hyperemia is not detectable by scintigraphy may have similar (outstanding) outcomes, and thus should not be excluded from treatment.
Our aim was to assess the prognostic and predictive value of somatostatin receptor 2 (sstr2) in neuroendocrine tumors (NETs).
We established a tissue microarray and imaging database from NET patients that received sstr2-targeted radiopeptide therapy with yttrium-90-DOTATOC, lutetium-177-DOTATOC or alternative treatment. We used univariate and multivariate analyses to identify prognostic and predictive markers for overall survival, including sstr2-imaging and sstr2-immunohistochemistry.
We included a total of 279 patients. In these patients, sstr2-immunohistochemistry was an independent prognostic marker for overall survival (HR: 0.82, 95 % CI: 0.67 – 0.99, n = 279, p = 0.037). In DOTATOC patients, sstr2-expression on immunohistochemistry correlated with tumor uptake on sstr2-imaging (n = 170, p < 0.001); however, sstr2-imaging showed a higher prognostic accuracy (positive predictive value: +27 %, 95 % CI: 3 – 56 %, p = 0.025). Sstr2-expression did not predict a benefit of DOTATOC over alternative treatment (p = 0.93).
Our results suggest sstr2 as an independent prognostic marker in NETs. Sstr2-immunohistochemistry correlates with sstr2-imaging; however, sstr2-imaging is more accurate for determining the individual prognosis.
For the quantitative assessment of dopamine transporter (DAT) using [123I]FP-CIT single-photon emission computed tomography (SPECT) (DaTscan), anatomic standardization is preferable for achieving objective and user-independent quantification of striatal binding using a volume-of-interest (VOI) template. However, low accumulation of DAT in Parkinson’s disease (PD) would lead to a deformation error when using a DaTscan-specific template without any structural information. To avoid this deformation error, we applied computed tomography (CT) data obtained using SPECT/CT equipment to anatomic standardization.
We retrospectively analyzed DaTscan images of 130 patients with parkinsonian syndromes (PS), including 80 PD and 50 non-PD patients. First we segmented gray matter from CT images using statistical parametric mapping 12 (SPM12). These gray-matter images were then anatomically standardized using the diffeomorphic anatomical registration using exponentiated Lie algebra (DARTEL) algorithm. Next, DaTscan images were warped with the same parameters used in the CT anatomic standardization. The target striatal VOIs for decreased DAT in PD were generated from the SPM12 group comparison of 20 DaTscan images from each group. We applied these VOIs to DaTscan images of the remaining patients in both groups and calculated the specific binding ratios (SBRs) using nonspecific counts in a reference area. In terms of the differential diagnosis of PD and non-PD groups using SBR, we compared the present method with two other methods, DaTQUANT and DaTView, which have already been released as software programs for the quantitative assessment of DaTscan images.
The SPM12 group comparison showed a significant DAT decrease in PD patients in the bilateral whole striatum. Of the three methods assessed, the present CT-guided method showed the greatest power for discriminating PD and non-PD groups, as it completely separated the two groups.
CT-guided anatomic standardization using the DARTEL algorithm is promising for the quantitative assessment of DaTscan images.
[S-methyl-11C]-L-methionine ([11C]MET) uptake in the pancreas might be a central indicator of beta cell function. Since gastric emptying was recently shown to influence glycemic control in subjects after pancreaticoduodenectomy (PD, the surgical treatment of neoplasms of the pancreas head), we looked for imaginable relationships between gastric emptying, pre- and postprandial insulin concentrations, and [11C]MET uptake.
Nineteen tumor-free survivors after PD (age mean ± SD: 61 ± 8.7 yrs.; 10 male, 9 female) and 10 healthy controls (age: 27 ± 8.7 yrs.; 7 male, 3 female) were given a mixed test meal. One gram of paracetamol was ingested with the meal to evaluate the speed of gastric emptying. Insulin, glucose, and paracetamol plasma concentrations were measured before and over 180 minutes after ingestion. Beta cell function was calculated from fasting glucose and insulin plasma concentrations. Simultaneously, 800 MBq of [11C]MET were administered and the activity (maximum tissue standardized uptake values [SUVmax]) over the pancreas was measured at 15, 30, and 60 minutes after injection. Total integrated SUVmax (area under the curve [AUC]) and incremental SUVmax were calculated.
The uptake of [11C]MET in the pancreas was significantly higher (p < 0.0001) in controls compared to the PD group. Gastric emptying was significantly slower in controls compared to pancreatectomy subjects (p < 0.0001). Paracetamol AUC30 correlated with the SUVmax increment between 15 and 30 minutes (R2 = 0.27, p = 0.0263), suggesting a relationship between gastric emptying and the uptake of [11C]MET. Total integrated SUVmax correlated with insulin AUC60 (R2 = 0.66,p < 0.0001) in patients after PD. Multivariate regression analysis revealed insulin AUC60 and beta cell function, calculated from the fasting insulin to glucose ratio, as independent predictors of 11C-methionine uptake, i.e. total integrated SUVmax, in patients after PD (R2 = 0.78, p < 0.0001).
Postprandial [11C]MET uptake may represent basal and postprandial beta cell function. The findings suggest a possible usefulness of this imaging procedure for further studying beta cell function.
To propose an MR-based method for generating continuous-valued head attenuation maps and to assess its accuracy and reproducibility. Demonstrating that novel MR-based photon attenuation correction methods are both accurate and reproducible is essential prior to using them routinely in research and clinical studies on integrated PET/MR scanners.
Continuous-valued linear attenuation coefficient maps (“μ-maps”) were generated by combining atlases that provided the prior probability of voxel positions belonging to a certain tissue class (air, soft tissue, or bone) and an MR intensity-based likelihood classifier to produce posterior probability maps of tissue classes. These probabilities were used as weights to generate the μ-maps. The accuracy of this probabilistic atlas-based continuous-valued μ-map (“PAC-map”) generation method was assessed by calculating the voxel-wise absolute relative change (RC) between the MR-based and scaled CT-based attenuation-corrected PET images. To assess reproducibility, we performed pair-wise comparisons of the RC values obtained from the PET images reconstructed using the μ-maps generated from the data acquired at three time points.
The proposed method produced continuous-valued μ-maps that qualitatively reflected the variable anatomy in patients with brain tumor and agreed well with the scaled CT-based μ-maps. The absolute RC comparing the resulting PET volumes was 1.76 ± 2.33 %, quantitatively demonstrating that the method is accurate. Additionally, we also showed that the method is highly reproducible, the mean RC value for the PET images reconstructed using the μ-maps obtained at the three visits being 0.65 ± 0.95 %.
Accurate and highly reproducible continuous-valued head μ-maps can be generated from MR data using a probabilistic atlas-based approach.
Complete fracture healing is crucial for good patient outcomes. A major complication in the treatment of fractures is non-union. The pathogenesis of non-unions is not always clear, although implant-associated infections play a significant role, especially after surgical treatment of open fractures. We aimed to evaluate the value of [18F]FDG PET in suspected infections of non-union fractures.
We retrospectively evaluated 35 consecutive patients seen between 2000 and 2015 with suspected infection of non-union fractures, treated at a level I trauma center. The patients underwent either [18F]FDG PET/CT (N = 24), [18F]FDG PET (N = 11) plus additional CT (N = 8), or conventional X-ray (N = 3). Imaging findings were correlated with final diagnosis based on intraoperative culture or follow-up.
In 13 of 35 patients (37 %), infection was proven by either positive intraoperative tissue culture (N = 12) or positive follow-up (N = 1). [18F]FDG PET revealed 11 true-positive, 19 true-negative, three false-positive, and two false-negative results, indicating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 85 %, 86 %, 79 %, 90 %, and 86 %, respectively. The SUVmax was 6.4 ± 2.7 in the clinically infected group and 3.0 ± 1.7 in the clinically non-infected group (p <0.01). The SUVratio was 5.3 ± 3.3 in the clinically infected group and 2.6 ± 1.5 in the clinically non-infected group (p <0.01).
[18F]FDG PET differentiates infected from non-infected non-unions with high accuracy in patients with suspected infections of non-union fractures, for whom other clinical findings were inconclusive for a local infection. [18F]FDG PET should be considered for therapeutic management of non-unions.
Lu-DOTATATE (Lu-PRRT) is a valid therapeutic option in differentiated pancreatic neuroendocrine tumors (P-NETs). FDG PET seems to be an important prognostic factor in P-NETs. We evaluated the efficacy of Lu-PRRT and the role of FDG PET in 60 patients with advanced P-NETs.
From March 2008 to June 2011, 60 consecutive patients with P-NETs were enrolled in the study. Follow-up lasted until March 2016. Eligible patients were treated with two different total cumulative activities (18.5 or 27.8 GBq in 5 cycles every 6–8 weeks), according to kidney and bone marrow parameters.
Twenty-eight patients received a mean full activity (FA) of 25.9 GBq and 32 a mean reduced activity (RA) of 18.5 GBq. The disease control rate (DCR), defined as the sum of CR+PR+SD was 85.7 % in the FA group and 78.1 % in the RA group. Median progression-free survival (mPFS) was 53.4 months in the FA group and 21.7 months in the RA group (P = 0.353). Median overall survival (mOS) was not reached (nr) in FA patients and was 63.8 months in the RA group (P = 0.007). Fifty-five patients underwent an FDG PET scan before Lu-PRRT, 32 (58 %) showing an increased FDG uptake in tumor sites. mPFS was 21.1 months in FDG PET-positive patients and 68.7 months in the FDG PET-negative group (P < 0.0002), regardless of the total activity administered.
Both FA and RA are active in patients undergoing Lu-PRRT. However, an FA of 27.8 GBq of Lu-PRRT prolongs PFS and OS compared to an RA of 18.5 GBq. Our results indicate that FDG PET is an independent prognostic factor in this patient setting.
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Otolaryngology (ENT) Sub-Specialties
News-Medical.net ... and various sub-specialties. These include such disciplines as pediatrics, oncology, sinus disease, and surgery. Because of their range of capabilities, ENT surgeons might one day correct a child's tonsillitis and on the next day treat an adult's ... and more » |
Menopause: The time in a woman's life when menstrual periods permanently stop; it is also called the "change of life."
Menopause is defined as the time when there has been no menstrual periods for 12 consecutive months and no other biological or physiological cause can be identified. It is the end of fertility, the end of the childbearing years. (A woman may still, however, be able to become pregnant unless 12 consecutive months have passed without a period.)
A woman can usually tell if she is approaching menopause because her menstrual periods starts changing. The medical terms used to describe this time are "perimenopause" and the "menopause transition."
Natural menopause occurs when the ovaries naturally begin decreasing their production of the sex hormones estrogen and progesterone.
Induced menopause occurs if the ovaries are surgically removed (by bilateral oophorectomy) or damaged by radiation or drugs. Due to the abrupt cutoff of ovarian hormones, induced menopause causes the sudden onset of hot flashes and other menopause-related symptoms such as a dry vagina and a decline in sex drive. Early menopause (before age 40), whether natural or induced, carries a greater risk for heart disease and osteoporosis since there are more years spent beyond the protective cover of estrogen.
A "simple" hysterectomy (when the uterus but not the ovaries are removed) before natural menopause should not affect the production of sex hormones and so not cause menopause (unless the nerves or blood supply to the ovaries is damaged during the hysterectomy).
The timing of natural menopause is variable. In the western world, the average age at which menopause starts is now 51. Natural menopause can, however, be in a woman's 30s or 60s. Factors influencing the time of menopause include heredity (genetics) and cigarette smoking. Smokers (and former smokers) reach menopause an average of 2 years before women who have never smoked.
There is no relation between the time of a woman's first period and her age at menopause. The age at menopause is not influenced by a woman's race, height, number of children or use of oral contraceptives.
The changes of the menopause transition (perimenopause) begin about 6 years before the natural menopause. This is a time when the levels of hormones produced by the aging ovaries fluctuate, leading to irregular menstrual patterns (irregularity in the length of the period, the time between periods, and the level of flow) and hot flashes (a sudden warm feeling with blushing). Other changes associated with the perimenopause and menopause include night sweats, mood swings, vaginal dryness, fluctuations in sexual desire (libido), forgetfulness, trouble sleeping and fatigue (probably from the loss of sleep).
Recovery of the internal mucosal lining is the most problematic step in nasal reconstruction. Restoration of both aesthetic and functional components should be the goal to be pursued. For this purpose, we performed a study for functional evaluation of the restored mucosa after nasal reconstruction.
From April 2009 to May 2016, 10 patients in whom the galea was used to reconstruct the nasal lining were selected from our casuistic of nasal reconstruction. In order to visualize the nasal and nasopharyngeal cavity, an antero-posterior rhinoendoscopy was performed in all patients. Additionally, patients were asked to complete a visual analogue scale (VAS) evaluation regarding nasal obstruction. Active anterior rhinomanometry analysis, olfactometry analysis and a cytologic examination were also conducted.
Near-normal results in nasal obstruction evaluation were reported subjectively by patients. Near-normal inspiratory values were obtained using rhinomanometry. Average values of TDI (threshold, discrimination and identification), a comprehensive olfactometric parameter, were essentially normal. Cytological sampling examination did not reveal any substantial abnormal variation.
Based on our morphological and functional results, we can assert that the forehead flap in association with galea for lining is a safe and practical surgical technique in total nasal reconstruction.
Level of Evidence: Level V, prognostic study
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Common Ear, Nose & Throat (ENT) Procedures
News-Medical.net Tympanoplasty is reconstructive surgery involving the eardrum. In stapedectomy, a surgeon removes at least part of the bone in the middle ear. Malignancies in the head and neck – such as larynx, oral, and temporal bone cancers - may require ENT surgery. and more » |
LIM domain proteins have been identified as essential modulators of cardiac biology and pathology; however, it is unclear which role the cysteine-rich LIM-only protein (CRP)4 plays in these processes. In studying CRP4 mutant mice, we found that their hearts developed normally but lack of CRP4 exaggerated multiple parameters of the cardiac stress response to the neurohormone angiotensin II (Ang II). Aiming to dissect the molecular details we find a link between CRP4 and the cardioprotective cGMP pathway, as well as a multiprotein complex comprising well-known hypertrophy-associated factors. Significant enrichment of the cysteine-rich intestinal protein (CRIP)1 in murine hearts lacking CRP4, as well as severe cardiac defects and premature death of CRIP1 and CRP4 morphant zebrafish embryos further support the notion that depleting CRP4 is incompatible with a proper cardiac development and function. Together, amplified Ang II signaling identified CRP4 as a novel antiremodeling factor regulated, at least to some extent, by cardiac cGMP.—Straubinger, J., Boldt, K., Kuret, A., Deng, L., Krattenmacher, D., Bork, N., Desch, M., Feil, R., Feil, S., Nemer, M., Ueffing, M., Ruth, P., Just, S., Lukowski, R. Amplified pathogenic actions of angiotensin II in cysteine-rich LIM-only protein 4 negative mouse hearts.
Cancer cachexia is a multifactorial syndrome characterized by body weight loss, atrophy of adipose tissue (AT) and systemic inflammation. However, there is restrict information regarding the mechanisms of immunometabolic response in AT from cancer cachexia. Male Wistar rats were inoculated with 2 x 107 of Walker 256 tumor cells [tumor bearing (TB)]. The mesenteric AT (MeAT) was collected on d 0, 4, 7 (early stage), and 14 (cachexia stage) after tumor cell injection. Surgical biopsies for MeAT were obtained from patients who had gastrointestinal cancer with cachexia. Lipolysis showed an early decrease in glycerol release in TB d 4 (TB4) rats in relation to the control, followed by a 6-fold increase in TB d 14 (TB14), whereas de novo lipogenesis was markedly lower in the incorporation of glucose into fatty acids in TB14 during the development of cachexia. CD11b and CD68 were positive in TB rats (d 7 and 14, respectively). In addition, we found cachexia stage results similar to those of animals in MeAT from patients: an increased presence of CD68+, iNOS2+, TNFα+, and HSL+ cells. In summary, translational analysis of MeAT from patients and animal model of cancer cachexia enabled us to identify early disruption in Adl turnover and subsequent inflammatory response during the development of cancer cachexia.—Henriques, F. S., Sertié, R. A. L., Franco, F. O., Knobl, P., Neves, R. X., Andreotti, S., Lima, F. B., Guilherme, A., Seelaender, M., Batista, M. L., Jr. Early suppression of adipocyte lipid turnover induces immunometabolic modulation in cancer cachexia syndrome.
Cancer has been described using metaphors for over 4 decades. However, little is known about healthy adolescents’ perspectives of cancer using metaphors. This paper reports on findings specific to adolescents’ perspectives of cancer using metaphors. The findings emerged from a qualitative ethnographic study that sought to understand Canadian adolescents’ conceptualisation of cancer and cancer prevention.
DesignTo arrive at a detailed description, data were obtained using individual interviews, focus groups and photovoice.
Setting6 high schools from a western Canada province.
Participants75 Canadian adolescents.
ResultsUse of 4 metaphors emerged from the data: loss (cancer as the sick patient and cancer as death itself); military (cancer as a battle); living thing (haywire cells and other living things) and faith (cancer as God's will) metaphors, with the loss and military metaphors being the ones most frequently used by adolescents. Adolescents’ descriptions of cancer were partly informed by their experiences with family members with cancer but also what occurs in their social worlds including mass media. Adolescents related cancer to emotions such as sadness and fear. Accordingly, more holistic and factual cancer descriptions, education and psychosocial support are needed to direct cancer messaging and clinical practice.
ConclusionsFindings from this study suggest that the public and healthcare providers be more aware of how they communicate cancer messages.
The aim of this study was to assess general practitioner (GP) management practices related to skin cancer prevention and screening during standard medical encounters.
SettingData on medical encounters addressing skin cancer issues were obtained from a French database containing information from 17 019 standard primary care consultations.
ParticipantsData were collected between December 2011 and April 2012 by 54 trainees who reported the regular practice of 128 GPs using the International Classification of Primary Care.
Outcome measuresReasons for encounters and the following care processes were recorded: counselling, clinical examinations and referral to a specialist. Medical encounters addressing skin cancer issues were compared with medical encounters that addressed other health problems using a multivariate analysis.
ResultsOnly 0.7% of medical encounters addressed skin cancer issues. When patients did require management of a skin cancer-related issue, this was more likely initiated by the doctor than the patient (70.7% vs 29.3%; p<0.001). Compared with medical encounters addressing other health problems, encounters that addressed skin cancer problems required more tasks (3.7 vs 2.5; p<0.001) and lasted 1 min and 20 s longer (p=0.003). GPs were less involved in clinical examinations (67.5% vs 97.1%; p<0.001), both complete (7.3% vs 22.3%, p<0.001) and partial examinations (60.2% vs 74.9%), and were less involved in counselling (5.7% vs 16.9%; p<0.001). Patients presenting skin cancer issues were referred to a specialist more often than patients consulting for other health problems (39.0% vs 12.1%; p<0.001). GPs performed a biopsy in 6.7% of all skin cancer-related encounters.
ConclusionsThis study demonstrates discrepancies between the high prevalence of skin cancer and the low rate of medical encounters addressing these issues in general practice. Our findings should be followed by qualitative interviews to better understand the observed practices in this field.
The prognostic value of lactate in the setting of an emergency department (ED) has not been studied extensively. The goal of this study was to assess 28-day mortality in ED patients in whom lactate was elevated (≥4.0 mmol/L), <4.0 mmol/L or not determined and to study the impact of the underlying cause of hyperlactatemia, that is, type A (tissue hypoxia) or type B (non-hypoxia), on mortality.
DesignRetrospective study.
SettingA secondary and tertiary referral centre in the Netherlands.
Materials and methodsAll internal medicine patients with hyperlactatemia (≥4.0 mmol/L) at the ED between January 2011 and October 2014 were included in this study. Samples of patients with lactate levels <4.0 mmol/L and of patients in whom no lactate was measured were included as a reference.
ResultsIn 1144 of 19 822 patients (5.8%), lactate was measured. Hyperlactatemia (n=197) was associated with a higher 28-day mortality than in those with lactate <4.0 mmol/L (40.6% vs 18.5%; p<0.001) and in those without lactate measurements (9.5%). Type A hyperlactatemia, present in 84% of those with hyperlactatemia, was associated with higher mortality than type B hyperlactatemia (45.8% vs 12.5%, p=0.001).
ConclusionsThis study demonstrates that the prognostic value of lactate depends largely on the underlying cause and the population in whom lactate has been measured. Prospective studies are required to address the true added value of lactate at the ED.
Stroke frequently results in balance disorders, leading to lower levels of activity and a diminution in autonomy. Current physical therapies (PT) aiming to reduce postural imbalance have shown a large variety of effects with low levels of evidence. The objectives are to determine the efficiency of PT in recovering from postural imbalance in patients after a stroke and to assess which PT is more effective.
Methods and analysisWe will search several databases from inception to October 2015. Only randomised controlled trials assessing PT to recover from poststroke postural imbalance in adults will be considered.
Outcome measures will be the Berg Balance Scale (BBS), the Postural Assessment Scale for Stroke (PASS), the ‘weight-bearing asymmetry’ (WBA), the ‘centre of pressure’ (COP) and the ‘limit of stability’ (LOS). WBA, COP and LOS are measured by a (sitting or standing) static evaluation on force plate or another device.
Two independent reviewers will screen titles, abstracts and full-text articles, evaluate the risk of bias and will perform data extraction. In addition to the outcomes, measures of independence will be analysed. This study will aim at determining the effects of PT on the function (WBA, COP, LOS), the activity (BBS, PASS) and the independence of patients. Subgroup analyses will be planned according to the location of brain lesion (hemispheric, brainstem or cerebellum), the time since stroke (early, late, chronic), the PT (type, main aim (direct effect or generalisation), overall duration), the type of approaches (top-down or bottom-up) and the methodological quality of studies.
Ethics and disseminationNo ethical statement will be required. The results will be published in a peer-reviewed journal. This meta-analysis aims at managing the rehabilitation after postural imbalance by PT after a stroke.
Trial registration numberProspero CRD42016037966;Pre-results.
To calculate the prevalence of disabling chronic pain (DCP) and to offer a more representative and accurate estimation by applying different calibration techniques.
Settings2011 Andalusian Health Survey, a cross-sectional population survey based on face-to-face home interviews.
Participants6507 people aged 16 years or older and living in Andalusia, Spain.
OutcomesDesign weights, linear calibration based on marginals and on crossings, and model-assisted calibration were used to estimate the prevalence and variance of DCP, for the whole sample and for the domains of sex and age groups (16–44; 45–64; +65).
ResultsCalibration variables were sex, age groups and educational level. In the whole sample, DCP prevalence calibration reduced by more than 5.2% and 8.2% the estimated prevalences and variances, respectively, obtained with the design weights. Regarding the domains, prevalence reductions are from 33% to 1%, and variance reductions are from 0.2% to 1%. Model-assisted calibration is the best technique to estimate DCP prevalence for the whole population and crossing calibration for their domains, although with almost no differences compared to marginal calibration.
ConclusionsThe validity and accuracy of estimations of DCP prevalence are improved by calibration adjustments. Model-assisted calibrated prevalence of DCP is 10.78% for the whole population, being at least 2-fold higher in women in all age groups. The results and methodology developed could be useful in clinical and population-based studies on chronic pain and disability.
Communication and teamwork failures have frequently been identified as the root cause of adverse events and complications in surgery. Few studies have examined contextual factors that influence teams’ non-technical skills (NTS) in surgery. The purpose of this prospective study was to identify and describe correlates of NTS.
MethodsWe assessed NTS of teams and professional role at 2 hospitals using the revised 23-item Non-TECHnical Skills (NOTECHS) and its subscales (communication, situational awareness, team skills, leadership and decision-making). Over 6 months, 2 trained observers evaluated teams’ NTS using a structured form. Interobserver agreement across hospitals ranged from 86% to 95%. Multiple regression models were developed to describe associations between operative time, team membership, miscommunications, interruptions, and total NOTECHS and subscale scores.
ResultsWe observed 161 surgical procedures across 8 teams. The total amount of explained variance in NOTECHS and its 5 subscales ranged from 14% (adjusted R2 0.12, p<0.001) to 24% (adjusted R2 0.22, p<0.001). In all models, inverse relationships between the total number of miscommunications and total number of interruptions and teams’ NTS were observed.
ConclusionsMiscommunications and interruptions impact on team NTS performance.
Ixekizumab (Taltz®) is a subcutaneously administered, humanized anti-interleukin-17A monoclonal antibody indicated for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy (USA and EU) or phototherapy (USA). In the phase 3 UNCOVER trials in this patient population, ixekizumab was superior to placebo or etanercept in terms of the proportion of patients achieving a ≥75% reduction from baseline in the Psoriasis Area and Severity Index and in those achieving a static Physician Global Assessment score of 0 or 1, after 12 weeks of induction treatment. Clinical responses to ixekizumab were seen as early as week 1. Patients receiving ixekizumab also reported improvements in health-related quality of life, itching, and work productivity. Clinical responses to ixekizumab were sustained during additional 48 weeks of maintenance treatment. Ixekizumab was generally well tolerated and exhibited low immunogenicity in the UNCOVER trials during up to 60 weeks of therapy. Currently available data indicate that ixekizumab is an effective and generally well tolerated treatment option for patients with moderate to severe plaque psoriasis. It has the potential advantage of one maintenance dose for every 4 weeks.
The study purposes to evaluate nanocrystalline biopolymeric nanoparticles encapsulating methotrexate and dexamethasone with high biocompatibility, enhanced therapeutic efficacy and reduced toxicity.
Chitosan nanoparticles were prepared by ionic gelation, and Methotrexate (MTX) and Dexamethasone (DEX) were loaded during the preparation and screened for their in vitro efficacy in HEK and RAW264.7 cells, ex vivo and in vivo efficacy.
FTIR confirmed the involvement of phosphoric group of sTPP with amine groups of chitosan and also role of hydrogen bonding involved in the preparation of MTXCHNP and DEXCHNP. Controlled release patterns coupled with diffusion of drug were observed in two different buffers (PBS) at pH 7.4 and pH 5.8. The IC50 for MTXCHNP for HEK was 26.1 μg/ml and 7.7 μg/ml for RAW 264.7 cells. In DEXCHNP, the IC50 was 20.12 μg/ml for HEK and 7.37 μg/ml for RAW264.7 cells. Enhanced uptake of FITC-CHNP by RAW cells indicated internalization of nanoparticles by phagocytosis. The enhanced release of drug at lower pH justified increased cytotoxicity. Negligible ex-vivo hemolysis indicated the higher biocompatibility of the nanoparticles. 99mTc-CHNP exhibited maximum absorption in blood circulation in 3 h, followed by hepatic metabolism and renal clearance. Higher in-vivo anti-arthritic activity and antioxidant activity was observed post-intraperitoneal (i.p.) injections by both MTXCHNP and DEXCHNP when compared to MTX (0.75 mg/Kg by i.p. route) and DEX (0.2 mg/Kg/i.p./daily) per se.
The nanocrystalline biopolymeric nanoparticles were stable, biocompatible and have potential to be administered through i.p. route with minimal toxicity and high efficacy.
Skin permeation/penetration enhancers are substances that enable drug delivery through or into the skin.
To search for new enhancers with high but reversible activity and acceptable toxicity, we synthesized a series of d-glucose derivatives, both hydrophilic and amphiphilic.
Initial evaluation of the ability of these sugar derivatives to increase permeation and penetration of theophylline through/into human skin compared with a control (no enhancer) or sorbitan monolaurate (Span 20; positive control) revealed dodecyl 6-amino-6-deoxy-α-d-glucopyranoside 5 as a promising enhancer. Furthermore, this amino sugar 5 increased epidermal concentration of a highly hydrophilic antiviral cidofovir by a factor of 7. The effect of compound 5 on skin electrical impedance suggested its direct interaction with the skin barrier. Infrared spectroscopy of isolated stratum corneum revealed no effect of enhancer 5 on the stratum corneum proteins but an overall decrease in the lipid chain order. The enhancer showed acceptable toxicity on HaCaT keratinocyte and 3T3 fibroblast cell lines. Finally, transepidermal water loss returned to baseline values after enhancer 5 had been removed from the skin.
Compound 5, a dodecyl amino glucoside, is a promising enhancer that acts through a reversible interaction with the stratum corneum lipids.
To prepare the supramolecular cocrystals of gliclazide (GL, a BCS class II drug molecule) via mechanochemical route, with the goal of improving physicochemical and biopharmaceutical properties.
Two cocrystals of GL with GRAS status coformers, sebacic acid (GL-SB; 1:1) and α-hydroxyacetic acid (GL-HA; 1:1) were screened out using liquid assisted grinding. The prepared cocrystals were characterized using thermal and analytical techniques followed by evaluation of antidiabetic activity and pharmacokinetic parameters.
The generation of new, single and pure crystal forms was characterized by DSC and PXRD. The crystal structure determination from PXRD revealed the existence of both cocrystals in triclinic (P-1) crystal system. The hydrogen bonded network, determined by material studio was well supported by shifts in FTIR and SSNMR. Both the new solid forms displayed improved solubility, IDR, antidiabetic activity and pharmacokinetic parameters as compared to GL.
The improvement in these physicochemical and biopharmaceutical properties corroborated the fact that the supramolecular cocrystallization may be useful in the development of pharmaceutical crystalline materials with interesting network and properties.
Current marketed dry powder inhalers utilize the energy from patient inspiration to fluidize and disperse bulk powder agglomerates into respirable particles. Variations in patient inspiratory flow profiles can lead to marked differences in total lung dose (TLD), and ultimately patient outcomes for an inhaled therapeutic. The present review aims to quantitate the flow rate dependence in TLD observed for a number of drug/device combinations using a new metric termed the Q index. With this data in hand, the review explores key attributes in the design of the formulation and device that impact flow rate dependence. The review also proposes alternative in vitro methods to assess flow rate dependence that more closely align with in vivo observations. Finally, the impact of variations in flow rate on lung function for inhaled bronchodilators is summarized.
