Randomized trial comparing intraoral ultrasound to landmark-based needle aspiration in patients with suspected peritonsillar abscess.
Traditionally, emergency physicians (EPs) have used anatomic landmark-based needle aspiration to drain peritonsillar abscesses (PTAs). If this failed, an imaging study and/or consultation with another service to perform the drainage is obtained. Recently, some EPs have used ultrasound (US) to guide PTA drainage. This study seeks to determine which initial approach leads to greater successful drainage. The primary objective of this study was to compare the diagnostic accuracy of EPs for detecting PTA or peritonsillar cellulitis (PTC) using either intraoral US or initial needle aspiration after visual inspection (the landmark technique [LM]). Secondary objectives included the successful aspiration of purulent material in those patients with a PTA in each arm, the use of computed tomography (CT) scanning in each arm, and the otolaryngology (ENT) consultation rate in each arm. This was a prospective, randomized, controlled clinical trial of a convenience sample of adult patients who presented to a single, large, urban university hospital. Patients were enrolled if they presented with a constellation of signs and symptoms that were judged to be a PTA. These patients were randomized to receive intraoral US or to undergo LM drainage. The US was performed using an 8-5 MHz intracavitary transducer immediately prior to the procedure. The probe was then withdrawn and the provider who did the US also performed the needle aspiration. The LM was performed using visual landmarks in a superior to inferior approach until pus was obtained or at least two sticks were performed. Anesthesia was standardized. Patients returned for follow-up in 2 days where a final diagnosis was rendered. There were 28 patients enrolled, with 14 in each arm. US established the correct diagnosis more often than LM [(100%, 95% confidence interval [CI] = 75% to 100% vs. 64%, 95% CI = 39% to 84%; p = 0.04)]. US also led to more successful aspiration of purulent material by the EP than LM in patients with PTA [(100%, 95% CI =63% to 100% vs. 50%, 95% CI = 24% to 76%; p = 0.04)]. The ENT consult rate was 7% (95% CI = 0% to 34%) for US versus 50% (95% CI = 27% to 73%) for LM (p = 0.03). The CT usage rate was 0% for US versus 35% for LM (p = 0.04). An initial intraoral US performed by EPs can reliably diagnose PTC and PTA. Additionally, using intraoral US to assist in the drainage of PTAs with needle aspiration leads to greater success compared to the traditional method of LM relying on physical exam alone.


Acute effect of simvastatin on inflammation and oxidative stress in chronic kidney disease.
Inflammation and oxidative stress (OS) are risk factors for cardiovascular disease in chronic kidney disease (CKD). This study assessed the acute effect of simvastatin on inflammatory and OS markers in stage 3 and 4 CKD patients. Randomized, placebo-controlled, double-blind, cross-over study comprising 66 patients who were randomized to simvastatin (20 mg/day) or placebo for two 8-week periods. Glomerular filtration rate (GFR), lipid profile, C-reactive protein (CRP), fibrinogen, carbonyls and total radical-trapping antioxidant potential (TRAP) were measured. Interactions between potential confounding factors, such as diabetes mellitus, malnutrition, drug use, hypercholesterolemia and treatment response were assessed through the course of inflammatory and OS levels. Thirty-three patients were randomized to simvastatin/placebo (S-P), and 33 to placebo/simvastatin (P-S). Simvastatin significantly reduced total and LDL cholesterol (pretreatment vs. posttreatment: p=0.0001 and p=0.0001, respectively) in both periods. No differences were seen in CRP, fibrinogen, carbonyls and TRAP levels between S-P and P-S groups at the end of the 2 study periods. GFR was similar in both groups and negatively correlated to fibrinogen (r=-0.25, p=0.04) and TRAP (r=-0.27, p=0.03). No interactions were found between confounding factors and response to simvastatin. There was no interference of either a period effect or any carryover effect on study results. The use of simvastatin in CKD patients acutely did not reduce serum inflammation or OS markers. Possibly higher doses and/or longer treatment course of statin are required to produce drug pleiotropic effects in nondialysis CKD patients.


Systematic review: Helicobacter pylori infection and impaired drug absorption.
Impaired acid secretion may affect drug absorption and may be consequent to corporal Helicobacter pylori-gastritis, which may affect the absorption of orally administered drugs. To focus on the evidence of impaired drug absorption associated with H. pylori infection. Data sources were the systematic search of MEDLINE/EMBASE/SCOPUS databases (1980-April 2008) for English articles using the keywords: drug malabsorption/absorption, stomach, Helicobacter pylori, gastritis, gastric acid, gastric pH, hypochlorhydria, gastric hypoacidity. Study selection was made from 2099 retrieved articles, five studies were identified. Data were extracted from selected papers, investigated drugs, study type, main features of subjects, study design, intervention type and results were extracted. In all, five studies investigated impaired absorption of l-dopa, thyroxine and delavirdine in H. pylori infection. Eradication treatment led to 21-54% increase in l-dopa in Parkinson's disease. Thyroxine requirement was higher in hypochlorhydric goitre with H. pylori-gastritis and thyrotropin levels decreased by 94% after treatment. In H. pylori- and HIV-positive hypochlorhydric subjects, delavirdine absorption increased by 57% with orange juice administration and by 150% after eradication. A plausible mechanism of impaired drug absorption is decreased acid secretion in H. pylori-gastritis patients. Helicobacter pylori infection and hypochlorhydria should be considered in prescribing drugs the absorption of which is potentially affected by intragastric pH.


Tumour eradication using synchronous thermal ablation and Hsp90 chemotherapy with protein engineered triblock biopolymer-geldanamycin conjugates.
Hepatocellular carcinoma (HCC) suffers high tumour recurrence rate after thermal ablation. Heat shock protein 90 (Hsp90) induced post-ablation is critical for tumour survival and progression. A combination therapy of thermal ablation and polymer conjugated Hsp90 chemotherapy was designed and evaluated for complete tumour eradication of HCC. A thermo-responsive, elastin-like polypeptide (ELP)-based tri-block biopolymer was developed and conjugated with a potent Hsp90 inhibitor, geldanamycin (GA). The anti-cancer efficacy of conjugates was evaluated in HCC cell cultures with and without hyperthermia (43 °C). The conjugates were also administered twice weekly in a murine HCC model as a single treatment or in combination with single electrocautery as the ablation method. ELP-GA conjugates displayed enhanced cytotoxicity in vitro and effective heat shock inhibition under hyperthermia. The conjugates alone significantly slowed the tumour growth without systemic toxicity. Four doses of thermo-responsive ELP-GA conjugates with concomitant simple electrocautery accomplished significant Hsp90 inhibition and sustained tumour suppression. Hsp90 inhibition plays a key role in preventing the recurrence of HCC, and the combination of ablation with targeted therapy holds great potential to improve prognosis and survival of HCC patients.


Accuracy of Computed Tomographic Angiography and Single-Photon Emission Computed Tomography-Acquired Myocardial Perfusion Imaging for the Diagnosis of Coronary Artery Disease.
Establishing the diagnosis of coronary artery disease (CAD) in symptomatic patients allows appropriately allocating preventative measures. Single-photon emission computed tomography (CT)-acquired myocardial perfusion imaging (SPECT-MPI) is frequently used for the evaluation of CAD, but coronary CT angiography (CTA) has emerged as a valid alternative. We compared the accuracy of SPECT-MPI and CTA for the diagnosis of CAD in 391 symptomatic patients who were prospectively enrolled in a multicenter study after clinical referral for cardiac catheterization. The area under the receiver operating characteristic curve was used to evaluate the diagnostic accuracy of CTA and SPECT-MPI for identifying patients with CAD defined as the presence of ≥1 coronary artery with ≥50% lumen stenosis by quantitative coronary angiography. Sensitivity to identify patients with CAD was greater for CTA than SPECT-MPI (0.92 versus 0.62, respectively; P<0.001), resulting in greater overall accuracy (area under the receiver operating characteristic curve, 0.91 [95% confidence interval, 0.88-0.94] versus 0.69 [0.64-0.74]; P<0.001). Results were similar in patients without previous history of CAD (area under the receiver operating characteristic curve, 0.92 [0.89-0.96] versus 0.67 [0.61-0.73]; P<0.001) and also for the secondary end points of ≥70% stenosis and multivessel disease, as well as subgroups, except for patients with a calcium score of ≥400 and those with high-risk anatomy in whom the overall accuracy was similar because CTA's superior sensitivity was offset by lower specificity in these settings. Radiation doses were 3.9 mSv for CTA and 9.8 for SPECT-MPI (P<0.001). CTA is more accurate than SPECT-MPI for the diagnosis of CAD as defined by conventional angiography and may be underused for this purpose in symptomatic patients. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00934037.


Combined Effect of Matrix Topography and Stiffness on Neutrophil Shape and Motility.
The crawling behavior of leukocytes is driven by the cell morphology transition, which is a direct manifestation of molecular motor machinery. The topographical anisotropy and mechanical stiffness of the substrates are the main physical cues that affect leukocytes' shape generation and migratory responses. However, their combined effects on the cell morphology and motility have been poorly understood, particularly for neutrophils, which are the fastest reacting leukocytes against infections and wounds. Here, spatiotemporally correlated physical parameters are shown, which determine the neutrophil shape change during migratory processes, in response to surface topography and elasticity. Guided crawling and shape generation of individual neutrophils, activated by a uniform concentration of a chemoattractant, are analyzed by adopting elasticity-tunable micropatterning and live cell imaging techniques. Whole cell-level image analysis is performed based on a planar geometric quantification of cell shape and motility. The findings show that the pattern anisotropy and elastic modulus of the substrate induce synergic effects on the shape anisotropy, deformability, and polarization/alignment of crawling neutrophils. How the morphology-motility relationship is affected by different surface microstructures and stiffness is demonstrated. These results imply that the neutrophil shape-motility correlations can be utilized for controlling the immune cell functions with predefined physical microenvironments.


Plasma microRNA-9 as a diagnostic and prognostic biomarker in patients with esophageal squamous cell carcinoma.
Purpose Emerging evidence indicates that circulating microRNAs (miRs) might act as noninvasive biomarkers for cancer diagnosis and prognosis. We examined the expression pattern and clinical significance of plasma miR-9 in patients with esophageal squamous cell carcinoma (ESCC). Methods Venous blood samples (6 mL) were collected from 131 patients with ESCC and 131 healthy controls, and the plasma miR-9 concentration was detected by reverse transcription polymerase chain reaction. The association of plasma miR-9 expression with clinicopathologic factors and survival of patients with ESCC was evaluated. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the clinical value of plasma miR-9 for ESCC diagnosis. Results The plasma miR-9 expression levels in patients with ESCC were significantly upregulated compared with normal controls. High plasma miR-9 concentrations were significantly correlated with poor tumor differentiation, large tumor size, deep local invasion, lymph node metastasis, advanced clinical stage, and poor survival. ROC curve analysis showed that the plasma miR-9 concentration could efficiently distinguish patients with ESCC from healthy controls. Multivariate survival analysis confirmed plasma miR-9 as an independent prognostic factor for ESCC. Conclusions Plasma miR-9 expression was upregulated in ESCC and might act as a novel diagnostic and prognostic biomarker.


LINC01232 Promotes Gastric Cancer Proliferation through Interacting with EZH2 to Inhibit the Transcription of KLF2.
To clarify the role of long intergenic nonprotein-coding RNA 1232 (LINC01232) in the progression of gastric cancer and the potential mechanism, we analyzed the expression of LINC01232 in TCGA database using the GEPIA online tool, and the LINC01232 level in gastric cancer cell lines was detected by quantitative real time-polymerase chain reaction (qRT-PCR) as well. Cell proliferation assay, colony formation assay, transwell assay and tumor formation experiment in nude mice were conducted to observe the biological behavior changes of gastric cancer cells through the influence of LINC01232 knockdown. LncATLAS database and subcellular isolation assay were used for subcellular distribution of LINC01232 in gastric cancer cells. The interaction among LINC01232, zeste homolog 2 (EZH2) and kruppel-like factor 2 (KLF2) was clarified by RNA-protein interaction prediction (RPISeq), RNA immunoprecipitation (RIP), qRT-PCR and chromatin immunoprecipitation (ChIP) assay. Rescue experiments were further conducted to elucidate the biological function of LINC01232/KLF2 axis in the progression of gastric cancer. LINC01232 was upregulated in stomach adenocarcinoma (STAD) tissues and gastric cancer lines. LINC01232 knockdown inhibited the proliferative capacities of gastric cancer cells in vitro, and impaired in vivo tumorigenicity. LINC01232 was mainly distributed in the cell nucleus where it epigenetically repressed KLF2 expression via binding to the enhancer of EZH2, which was capable of binding to promoter regions of KLF2 to induce histone H3 lysine 27 trimethylation (H3K27me3). LINC01232 exerts oncogenic activities in gastric cancer via inhibition of KLF2, and therefore, the knockdown of KLF2 could reverse the regulatory effect of LINC01232 in the proliferative ability of gastric cancer cells.


Repair of Orbital Post-Traumatic Wall Defects by Custom-Made TiNi Mesh Endografts.
Repairs of orbital post-traumatic and extensive malignant defects remain a major surgical challenge, in view of follow-up outcomes. Incorrect surgical management of injured facial structures results in cosmetic, ophthalmic, and social aftereffects. A custom-made knitted TiNi-based mesh (KTNM) endograft was employed to overcome post-surgical complications and post-resected lesions of the orbital area. Preoperative high-resolution computed tomography (CT) imaging and CAD modelling were used to design the customized KTNM in each case. Twenty-five patients underwent surgery utilizing the suggested technique, from 2014 to 2019. In all documented cases, resolution of the ophthalmic malfunction was noted in the early period. Follow-up observation evidenced no relapsed enophthalmos, hypoglobus, or diplopia as late complications. The findings emanating from our clinical observations allow us to claim that the KTNM indicated a high level of biocompatibility. It is simply modified intraoperatively to attach any desired shape/size for implantation and can also be screw-fixed, providing a good supporting ability. The KTNM precisely renders orbitozygomatic outlines and orbital floor, thus recovering the anatomical structure, and is regarded as an attractive alternative to Ti-based meshes and plates. Additionally, we report one of the studied cases, where good functional and cosmetic outcomes have been achieved.


Propylene glycol-associated renal toxicity from lorazepam infusion.
Using data from patients who developed elevations in serum creatinine concentrations while receiving continuous-infusion lorazepam, we sought to determine the correlations between the magnitude of serum creatinine concentration rise and each of the following variables: serum propylene glycol level, cumulative lorazepam dose, and duration of lorazepam administration. An additional objective was to identify clinical markers for propylene glycol toxicity. Retrospective chart review. Medical-surgical intensive care unit and burn unit at a university hospital. Eight patients who developed elevations in serum creatinine concentrations while receiving continuous-infusion lorazepam (range 2-28 mg/hr). The mean cumulative dose of lorazepam was 4305 mg (range 1200-10,920 mg), and the mean propylene glycol level determined at the time of peak serum creatinine concentration was 1103 microg/ml (range 186-3450 microg/ml). Serum creatinine concentrations increased in all eight patients during lorazepam infusion and decreased in seven within 3 days after stopping infusion. A weak-to-moderate correlation existed between the magnitude of the rise in serum creatinine concentration and propylene glycol level (r=0.53). A weak-to-moderate correlation also was identified between cumulative lorazepam dose and magnitude of serum creatinine concentration rise (r=0.43), and a strong-to-moderate correlation was found between duration of lorazepam infusion and magnitude of serum creatinine concentration rise (r=0.60). Propylene glycol levels were strongly correlated with both serum osmolality and osmol gap. The patients' increased serum creatinine concentrations are likely to have resulted from exposure to propylene glycol as a result of lorazepam infusion. Serum osmolality and osmol gap may be useful markers for propylene glycol toxicity.


Confirming a diagnosis of hereditary colorectal cancer: the impact of a Familial Bowel Cancer Registry in New Zealand.
The optimal management of familial bowel cancer is thought to involve specialised familial cancer units and registries that facilitate a multidisciplinary approach. We studied the impact this approach had on the investigation and management of affected families in our register. A review of the outcomes of assessment for 25 families was undertaken. These families have completed assessment by the Northern Regional Genetic Service Familial Bowel Cancer Registry because of the possibility of a hereditary bowel cancer syndrome. Details of the cancer history and screening advice known at the time of initial referral to the genetic service, and at the end of assessment, were compared. Detailed family history revealed 130 cancers, 90 of which were known at referral. Eighty-four cancers were confirmed, of which 73 belonged to the spectrum of cancers associated with hereditary nonpolyposis colorectal cancer (HNPCC). The mean age of diagnosis was 56.3 years. Eight families met the modified Amsterdam Criteria for the diagnosis of HNPCC, compared to four families at the time of referral. Familial hyperplastic polyposis was diagnosed in one family. 164 asymptomatic at-risk first-degree relatives were identified, 48 from families who met the Amsterdam criteria and were thereby recommended to have intensive colonoscopic screening. Assessment by the Familial Bowel Cancer Registry increased the number of cancers identified in families, thus facilitating a diagnosis of HNPCC in a third of the referred families and a diagnosis of hyperplastic polyposis in one other. Consequently specialised genetic testing and intensive colonoscopic surveillance could be targeted to the asymptomatic first-degree relatives most at risk. Ongoing coordination of colonoscopic surveillance by the registry for those individuals identified to have disease causing mutations or to be at-risk, is anticipated to reduce the number of deaths from colorectal cancer in these families.


Systematic review of the use of fibrin sealant to minimize perioperative allogeneic blood transfusion.
Fibrin sealants have become popular in improving perioperative haemostasis and reducing the need for allogeneic red cell transfusion. A systematic review of randomized controlled trials was conducted to examine the efficacy of fibrin sealants in reducing perioperative blood loss and allogeneic red blood cell transfusion. Studies were identified by computer searches of Medline, Embase, Current Contents, the Cochrane Library, manufacturer websites (to January 2001), and bibliographic searches of published articles. Trials were eligible for inclusion if they involved adult elective surgery and reported quantitative data on blood loss, the proportion of patients exposed to allogeneic red cell transfusion and/or the volume of blood transfused. Twelve trials met the criteria for inclusion. Fibrin sealants reduced the rate of allogeneic blood transfusion (relative risk 0.40 (95 per cent confidence interval (c.i.) 0.26 to 0.61); five trials with 275 subjects) and reduced blood loss (weighted mean difference--151.68 (95 per cent c.i. - 251.91 to - 51.46) ml; seven trials with 391 subjects). Generally, the trials were small and of poor methodological quality. Overall the results suggest that fibrin sealants are efficacious. Owing to lack of blinding, transfusion practices may have been influenced by knowledge of the patient's treatment status. This raises concern about blood transfusion practice as a response variable. Large methodologically rigorous trials of fibrin sealants with clinical outcomes are needed.


Contrast-enhanced MR microscopy of amyloid plaques in five mouse models of amyloidosis and in human Alzheimer's disease brains.
Gadolinium (Gd)-stained MRI is based on Gd contrast agent (CA) administration into the brain parenchyma. The strong signal increase induced by Gd CA can be converted into resolution enhancement to record microscopic MR images. Moreover, inhomogeneous distribution of the Gd CA in the brain improves the contrast between different tissues and provides new contrasts in MR images. Gd-stained MRI detects amyloid plaques, one of the microscopic lesions of Alzheimer's disease (AD), in APPSL/PS1M146L mice or in primates. Numerous transgenic mice with various plaque typologies have been developed to mimic cerebral amyloidosis and comparison of plaque detection between animal models and humans with new imaging methods is a recurrent concern. Here, we investigated detection of amyloid plaques by Gd-stained MRI in five mouse models of amyloidosis (APPSL/PS1M146L, APP/PS1dE9, APP23, APPSwDI, and 3xTg) presenting with compact, diffuse and intracellular plaques as well as in post mortem human-AD brains. The brains were then evaluated by histology to investigate the impact of size, compactness, and iron load of amyloid plaques on their detection by MRI. We show that Gd-stained MRI allows detection of compact amyloid plaques as small as 25 µm, independently of their iron load, in mice as well as in human-AD brains.


Subperitoneal hemorrhage.
Clinical diagnosis of subperitoneal hemorrhage can be made in a substantial percentage of cases by recognition of a quite constant syndrome-provided the possibility of bleeding is considered. Progressive anemia, as indicated by repeated counts of erythrocytes in the blood or by hematocrit determinations, is confirmation of the diagnosis. The majority of patients recover spontaneously under conservative management.Surgical intervention is indicated if repeated episodes of hemorrhage occur or if the volume of circulating blood cannot be maintained by repeated transfusions of whole blood.


The Evi-1 zinc finger myeloid transforming gene is normally expressed in the kidney and in developing oocytes.
Activation of the Evi-1 zinc finger gene is commonly associated with the transformation of murine leukemias and is involved in some cases of human AML involving rearrangements at chromosome 3q25. To determine the normal function of the gene, we have looked for expression in a variety of cell lines and tissues. The predominant sites of expression of the gene are in the kidney and ovary. In the kidney, expression is localized to the renal tubules in the corticomedullary junction. In the ovary, high levels of the Evi-1 protein are found in the cytoplasm of developing oocytes. The latter result suggests a potential role for the Evi-1 gene product in early oocyte development.


Vitamin E deficiency and neurologic disease.
During the recent resurgence of interest in the clinical uses of vitamin E, one of the major foci of attention has been the neurologic role of vitamin E in humans. Studies in patients with secondary vitamin E deficiency, caused by fat malabsorption disorders and total parenteral nutrition lacking an adequate supply of vitamin E, have elucidated a clinical disorder and histologic lesions of the nervous system and muscle that closely resemble those of experimental vitamin-E-deficient animal models. Investigations of the primary form of human vitamin E deficiency, the isolated vitamin E deficiency syndrome, have further substantiated the relationship between neurologic dysfunction and human vitamin E deficiency. It is now clear that vitamin E is an essential nutrient necessary for the optimal development and maintenance of the integrity and function of the human nervous system and skeletal muscle. The task for future study is to determine the mechanism by which vitamin E deficiency causes degeneration of selective regions of the nervous system and to investigate possible benefits of vitamin E supplementation in other neurologic disorders. In addition, further study of the isolated vitamin E deficiency syndrome promises to teach us more about normal physiologic mechanisms of vitamin E absorption and transport in humans.


Genotyping of Acanthamoeba T15: the environmental strain in Turkey.
Environmental sources are potential sources for the transmission of Acanthamoeba in humans and other mammals. A total of 50 water samples from hot springs and swimming pools, and 50 soil samples were taken from Adana, Afyon, Kutahya, Mersin and Nigde provinces in Turkey. Samples were analysed using 18S rRNA-DNA sequencing. Acanthamoeba griffini (T3), Acanthamoeba castellanii (T4) and Acanthamoeba jacobsi (T15) were found in water samples. Acanthamoeba griffini (T3) and Acanthamoeba castellanii (T4) were detected in soil samples. In Turkey, this was the first time that Acanthamoeba jacobsi (T15) was detected in water samples.


Neuroendocrine structures in normal and diseased human lung.
The increasing amount of histological, immunohistochemical and ultrastructural information on some endocrine secretions in human lung cancers suggest the need to revise the classification of neuroendocrine lesions on surgical material. The aim of the present investigation based on lung specimens removed surgically is to give further support to recent proposal for an updated classification of neuroendocrine lung carcinomas. Our study includes 58 squamous cell carcinomas, 58 adenocarcinomas, 6 large cell carcinomas, 27 neuroendocrine carcinomas, and 30 nontumourous cases. Using histological methods (HE, Alcian PAS, Grimelius silver impregnation), we illustrate the presence of neuroendocrine cells and neuroepithelial bodies with their pathological evolutions, ranging from hyperplasia, to dysplasia, and overt neoplasia. On the basis of our experience we propose the following classification of neuroendocrine carcinomas (NEC): typical carcinoids (NECNID), peripheral carcinoid or well-differentiated NEC (NECWED), NEC of intermediate or poorly differentiated type (NECINT) and NEC of small celled or microcytoma type (NECMIC).


Demonstration of IgG Fc receptors on spermatozoa and their utilization for the detection of circulating immune complexes in human serum.
The presence of Fc receptors, but not C3 receptors, on human and bovine spermatozoa was shown by sperm-induced rosette formation of antibody-treated ox erythrocytes and by immunofluorescence of aggregated human gammaglobulin (AHG) treated spermatozoa. Human and bovine spermatozoa bound AHG as well as circulating immune complexes (CIC) from human sera; monomeric IgG bound to these cells to a much lesser extent. Binding of AHG to the sperm surface also occurred when the AHG was suspended in either buffer or in serum that had been heated at 56 degrees C for 30 min. A bovine spermatozoa radioimmunoassay for the detection of immune complexes in human sera was developed and was shown to be comparable to the Raji cell radioimmunoassay (r = 0 . 81, P < 0 . 01) in the quantitation of soluble immune complexes from a variety of human sera. An enzyme-linked immunoassay was then developed, using bovine spermatozoa fixed to wells of microtitre plates, to simplify the immune complex detection assay. The technique provides an analysis that is rapid, does not require radioactive chemicals, expensive equipment, or cultured cells and yields values for immune complex determination both comparable and complementary to the Raji cell radioimmunoassay (r = 0 . 70, P < 0 . 01). The sperm assays detected soluble immune complexes in sera of vasectomized males, cancer patients and patients with autoimmune or dermatological diseases.


Treatment of celiac artery compression syndrome: does it really exist?
Celiac artery syndrome exists, although it remains controversial, and in some patients a firm diagnosis cannot be established. Duplex scanning or computed tomographic, magnetic resonance, or contrast aortography will confirm intermittent or permanent compression of the celiac artery by the crus of the diaphragm, the median arcuate ligament, or fibrous ganglionic tissue. Preoperative ganglion block and exercise gastric tonometry are useful diagnostic tools to predict better outcome after treatment. In patients with well-defined syndrome of chronic mesenteric and gastric ischemia or with exercise-induced pain, good results can be expected with division of the median arcuate ligament with open celiac artery reconstruction. Patients with atypical pain or history of psychiatric disorders only occasionally benefit from surgical repair. The role of primary stenting of celiac artery compression is still not well defined, and current data do not support the use of balloon-expandable stents. Laparoscopic division of the median arcuate ligament followed by celiac artery stenting is an effective, minimally invasive technique to manage selected patients with celiac artery compression syndrome.


Recent advances in design of immunogenic and effective naked DNA vaccines against cancer.
A variety of clinical trials for vaccines against cancer have provided evidence that DNA vaccines are well tolerated and have an excellent safety profile. DNA vaccines require much improvement to make them sufficiently effective against cancer in the clinic. Nowadays, it is clear that an increased antigen expression correlates with improved immunogenicity and it is critical to vaccine performance in large animals and humans. Similarly, additional strategies are required to activate effective immunity against poorly immunogenic tumour antigens. This review discusses very recent scientific references focused on the development of sophisticated DNA vaccines against cancer. We report a selection of novel and relevant patents employed to improve their immunogenicity through several strategies such as the use of tissue-specific transcriptional elements, nuclear localisation signalling, codon-optimisation and by targeting antigenic proteins to secretory pathway. Recent patents validating portions or splice variants of tumour antigens as candidates for cancer DNA vaccines with improved specificity, such as mesothelin and hTERT, are also discussed. Lastly, we review novel patents on the use of genetic immunomodulators, such as "universal" T helper epitopes derived from tetanus toxin, E. coli heat labile enterotoxin and vegetable proteins, as well as cytokines, chemokines or costimulatory molecules such as IL-6, IL-15, IL- 21 to amplify immunity against cancer.


Evaluation of Different 'Tensioning' of Apical Suspension in Women Undergoing Surgery for Prolapse and Urinary Incontinence.
According to the literature, restoration of pelvic organ prolapse also restores urinary continence. However, it is difficult to determine which exact surgical procedure actually led to urinary continence due to a lack of standardisation among these techniques. For example, an apical fixation is broadly defined in terms of type and shape of implanted material, anatomical fixation sides and tensioning. The aim of this study was to evaluate the effect of bilateral uterosacral ligament replacement with alloplastic tapes of defined lengths on symptoms of urinary incontinence. Patients with urinary incontinence and pelvic organ prolapse underwent an apical suspension. Thereby, both uterosacral ligaments (USL) were replaced by alloplastic structures of defined length. These alloplastic tapes had defined lengths in all patients of 9, 10, or 11 cm in length. They were sutured on both sides of the cervix, placed in the left and right peritoneal fold of the USL, and were sutured laterally to the prevertebral fascial layer of the sacral vertebra at the level of S2. Furthermore, all patients received additional transobturator tape. Pelvic organ prolapse was classified according to the Baden-Walker system, and urinary incontinence symptoms according to validated questionnaires. Four months after bilateral USL replacement, apical suspension was restored in all 31 patients. In addition, urinary continence was re-established in 18 out of these 31 patients (58%). The highest continence rate was observed in patients in which both USL were replaced with alloplastic tapes of 9 cm in length. The findings indicated the importance of USL integrity for urinary continence. In particular, a defined length for both USL seems to be important for (re-)establishing urinary continence.


Echocardiographic evaluation of left ventricular diastolic dysfunction in subclinical hypothyroidism: A case-control study.
To study the prevalence of left ventricular diastolic dysfunction (LVDD) in patients with subclinical hypothyroidism (SCH) and the response of LVDD to L-thyroxine therapy. This cross-sectional case-control study with one longitudinal arm included 67 patients with SCH attending a tertiary care hospital in Uttarakhand, India, and 67 age- and sex-matched healthy controls. LVDD was assessed by 2D, pulsed-wave Doppler (PWD), continuous wave Doppler (CWD), and tissue Doppler echocardiography (TDE). Patients with LVDD received L-thyroxine therapy with reassessment for LVDD 6 months later. SCH patients had a higher prevalence of LVDD than controls (13.43% versus 1.49%; p = 0.017). LVDD showed a significant association with gender (p = 0.004) and serum FT4 (p = 0.001). E velocity, E' velocity, A' velocity, iso-volumetric relaxation time (IVRT), E/A, and E'/A' ratios were significantly lower, while A velocity, deceleration time (DT), E/E' ratio, left atrial (LA) volume index, and peak tricuspid regurgitation (TR) velocity were significantly higher in cases than controls (p < 0.05 each). The E/A ratio correlated significantly with age, serum very low-density lipoprotein (VLDL), triglycerides (TG), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and high-density lipoprotein (HDL) (p < 0.05 each). E' velocity correlated significantly with age, serum total cholesterol, VLDL, and TG (p < 0.05 each), DT with serum total cholesterol (p = 0.047), and LA volume index with age (p = 0.021). Age (p = 0.016) and serum HDL (p = 0.029) were independent predictors of E/A ratio. Gender was an independent predictor for LVDD (p = 0.003). Echocardiographic indices for LVDD showed significant improvement after 6 months of L-thyroxine therapy (p < 0.05 each). LVDD occurs commonly in SCH patients. It can be detected timely using echocardiography and may be reversed by L-thyroxine therapy.


Genome-Wide Transcriptional Dynamics in the Companion Bacterial Symbionts of the Glassy-Winged Sharpshooter (Cicadellidae: Homalodisca vitripennis) Reveal Differential Gene Expression in Bacteria Occupying Multiple Host Organs.
The agricultural pest known as the glassy-winged sharpshooter (GWSS) or Homalodisca vitripennis (Hemiptera: Cicadellidae) harbors two bacterial symbionts, "Candidatus Sulcia muelleri" and "Ca Baumannia cicadellinicola," which provide the 10 essential amino acids (EAAs) that are limited in the host plant-sap diet. Although they differ in origin and symbiotic age, both bacteria have experienced extensive genome degradation resulting from their ancient restriction to specialized host organs (bacteriomes) that provide cellular support and ensure vertical transmission. GWSS bacteriomes are of different origins and distinctly colored red and yellow. While Sulcia occupies the yellow bacteriome, Baumannia inhabits both. Aside from genomic predictions, little is currently known about the cellular functions of these bacterial symbionts, particularly whether Baumannia in different bacteriomes perform different roles in the symbiosis. To address these questions, we conducted a replicated, strand-specific RNA-seq experiment to assay global gene expression patterns in Sulcia and Baumannia Despite differences in genomic capabilities, the symbionts exhibit similar profiles of their most highly expressed genes, including those involved in nutrition synthesis and protein stability (chaperonins dnaK and groESL) that likely aid impaired proteins. Baumannia populations in separate bacteriomes differentially express genes enriched in essential nutrient synthesis, including EAAs (histidine and methionine) and B vitamins (biotin and thiamine). Patterns of differential gene expression further reveal complexity in methionine synthesis. Baumannia's capability to differentially express genes is unusual, as ancient symbionts lose the capability to independently regulate transcription. Combined with previous microscopy, our results suggest that the GWSS may rely on distinct Baumannia populations for essential nutrition and vertical transmission.


The Brain Structural-Functional Vulnerability in Drug-Naive Children With Juvenile Idiopathic Arthritis: Insights From the Hippocampus.
Leveraging an integrative multimodal MRI paradigm to elaborate on the hippocampus-derived structural and functional changes in children and adolescents with juvenile idiopathic arthritis (JIA) and to explore potential correlations within the "joint-inflammation-brain" axis during the period of central neural system (CNS) development. Twenty-one patients with JIA all completed the multimodal MRI scanning, laboratory tests, and neuropsychological assessments; meanwhile, 23 matched controls were recruited. We then harnessed the spherical harmonics with a point distribution model (SPHARM-PDM) and the ROI-to-voxel functional connectivity (FC) to measure the hippocampal shape and hippocampo-cortical FC patterns. Correlation analysis was performed to explore the potential links in neuroimaging features with disease-related indices. Compared to controls, JIA patients only presented an atrophic tendency in the posterior part of the bilateral hippocampus. The hippocampo-cortical FC revealed the between-group divergences mainly located at the pain matrix, striatum, and temporal lobe. Remarkably, the enhanced FC between the right hippocampus and postcentral cortex is positively correlated with the disability index, while the weakened FC of right anterior hippocampus with right insula and that of left posterior hippocampus with left superior temporal gyrus was inversely related to the erythrocyte sedimentation rate and anxiety status, separately. As with macroscopic damages, the altered functional-connectome patterns of the hippocampus in JIA patients might be more sensitive to detect the early neuropathological changes. Moreover, the functional disturbances were demonstrated associated with the physical disability, inflammation, and emotional status. These findings may enlighten us on the underlying neuropathological mechanism of CNS comorbidities in JIA.


Brunner gland hamartoma with predominant adipose tissue and ciliated cysts.
We report an unusual case of Brunner gland hamartoma of the duodenal bulb with multiple ciliated cysts in a 43-year-old man. The patient presented with regurgitation. An endoscopy of the upper digestive tract revealed the presence of a pedunculated tumor of the first duodenum. Surgical resection of the antrum and first duodenum was performed. The polypoid lesion measured 3.5 cm and was located in the submucosa. It was composed of predominant adipose tissue containing hyperplastic lobules of Brunner gland and cystic ducts lined by ciliated cells. Brunner gland hamartoma is a rare benign duodenal lesion; it is usually composed of mature but disorganized tissues and is found most commonly in the duodenum. The presence of ciliated cells in the gut mucosa is a rare phenomenon, which has already been described in the esophagus and stomach. We report an unusual case of ciliated metaplasia in a duodenal Brunner gland hamartoma.


Peritonitis causes diaphragm weakness in rats.
Respiratory failure is a common and often lethal complication of severe peritonitis. Because this inflammatory process develops in the abdomen, adjacent to the diaphragm, we hypothesized that peritonitis might directly compromise diaphragm function. We tested this hypothesis using male Sprague-Dawley rats. We injected oyster glycogen into the rats' peritoneum, and 16 h later the peritoneum was lavaged for leukocyte analysis and muscle samples were excised. Contractile properties of diaphragm fiber bundles were measured in vitro. We found that neutrophils and macrophages were concentrated in peritoneal lavage fluid of experimental animals (p < 0.01) and were adherent to the abdominal surface of the diaphragm. Immunohistochemistry showed increases in inducible nitric oxide synthase in microvessels of the diaphragm and limb skeletal muscles but not in heart or spleen. Peritonitis decreased maximal force production by the diaphragm (23.6+/-0.6 versus 21.2+/-0.6 N/cm2; p < 0.05) and decreased the absolute forces developed at physiologic stimulus frequencies (> 30 Hz; p < 0.01), depressing the overall force-frequency relationship (p < 0.001). Peritonitis had little effect on acute muscular fatigue. These data demonstrate that peritonitis weakens the diaphragm in rats and suggest that humans with peritonitis may be predisposed to respiratory muscle dysfunction.


Temperature dependent exciton emission from herringbone aggregates of conjugated oligomers.
In this work, the effect of temperature, exciton bandwidth, and size on the photoluminescence spectra of defect-free two-dimensional herringbone aggregates of pi-conjugated oligomers such as oligophenylene vinylene and oligothiophene is investigated theoretically. The model is based on exciton-phonon coupling in two-dimensional herringbone lattices with the exciton deriving from the lowest optical (1Ag-->1Bu) transition and the phonon from the most strongly coupled intramolecular vibrational mode with frequency omega0. Simple analytical expressions are obtained for the line strengths of the emission origin (0-0) and first replica (0-1) as a function of the number of molecules comprising the aggregate, N, the free exciton bandwidth, WD, and the temperature, T. At a given temperature, the 0-0 emission intensity initially scales as N/Nth, where Nth is the superradiant threshold number, but eventually converges to NT/Nth, where NT is the size independent thermal coherence number. NT is inversely proportional to temperature and proportional to the exciton band curvature (omegac) near the band bottom; NT=1+4piomegac/kbT. In striking contrast, the 0-1 line strength is relatively insensitive to temperature and size, but scales as the inverse square of WD+omega0. The insensitivity of the first replica to the exciton coherence number makes the ratio of the 0-0 to 0-1 line strengths a measure of the exciton coherence number. The ratio can be used to test for crystal purity. Comparison to experiments on thin films of quaterthiophene shows that the thermal coherence size is given by NT approximately 1+450/T (K) and that superradiance, which requires NT>Nth, can only be observed at temperatures less than 1 K.


Biomarkers of sustained systemic inflammation and microvascular dysfunction associated with post-COVID-19 condition symptoms at 24 months after SARS-CoV-2-infection.
Comprehensive studies investigating sustained hypercoagulability, endothelial function, and/or inflammation in relation to post-COVID-19 (PCC) symptoms with a prolonged follow-up are currently lacking. Therefore, the aim of this single-centre cohort study was to investigate serum biomarkers of coagulation activation, microvascular dysfunction, and inflammation in relation to persisting symptoms two years after acute COVID-19. Patients diagnosed with acute SARS-CoV-2 infection between February and June 2020 were recruited. Outcome measures included the CORona Follow-Up (CORFU) questionnaire, which is based on an internationally developed and partially validated basic questionnaire on persistent PCC symptoms. Additionally, plasma biomarkers reflecting coagulation activation, endothelial dysfunction and systemic inflammation were measured. 167 individuals were approached of which 148 (89%) completed the CORFU questionnaire. At 24 months after acute infection, fatigue was the most prevalent PCC symptom (84.5%). Over 50% of the patients experienced symptoms related to breathing, cognition, sleep or mobility; 30.3% still experienced at least one severe or extreme (4 or 5 on a 5-point scale) PCC symptom. Multiple correlations were found between several PCC symptoms and markers of endothelial dysfunction (endothelin-1 and von Willebrand factor) and systemic inflammation (Interleukin-1 Receptor antagonist). No positive correlations were found between PCC symptoms and coagulation complexes. In conclusion, this study shows that at 24 months after acute COVID-19 infection patients experience a high prevalence of PCC symptoms which correlate with inflammatory cytokine IL-1Ra and markers of endothelial dysfunction, especially endothelin-1. Our data may provide a rationale for the selection of treatment strategies for further clinical studies. This study was performed in collaboration with the CORona Follow-Up (CORFU) study (NCT05240742, https://clinicaltrials.gov/ct2/show/ NCT05240742).


Development of a preparatory sensory information videotape for women receiving chemotherapy for breast cancer.
This study describes the development and testing of a preparatory sensory information (PSI) videotape for women receiving chemotherapy for breast cancer. In telephone interviews, 40 women described the sensations they experienced before, during, and after receiving chemotherapy. Sensations described by the women were linked with procedural and temporal elements identified by certified advanced practice oncology nurses to develop a script for the PSI videotape. Women currently receiving chemotherapy or who had completed chemotherapy within the last 6 months were asked to share their experiences on videotape. After editing, a 20-minute PSI videotape was produced. Pilot testing with a group of 20 women demonstrated that the intervention helped to prepare them for the sensory experiences associated with chemotherapy and was helpful in developing anticipatory coping and self-care behaviors.


Modeling the Pauli potential in the pair density functional theory.
In the ground state the pair density can be determined by solving a single auxiliary equation of a two-particle problem. A novel method for determining the Pauli potential entering this equation is presented and, starting from a reliable description of the pair density, an analytical expression is derived for atomic systems. Test calculations are presented for Be and isoelectronic C(2+) and O(4+) ions.


Implant placement after marsupialization of a dentigerous cyst.
This paper presents a case of a dentigerous cyst accompanied by a history of inflammation, resorption of the roots of the first molar and the lingual aspect of the distal root of the second molar, and devitalization of the 2 premolars. The treatment option chosen was marsupialization of the cyst, extraction of the involved teeth, endodontic treatment of both premolars, and implant insertion in the area of the first mandibular molar at a later stage. Twelve months postsurgery the area of interest was almost flattened and the radiographic examination revealed total disappearance of the radiolucency. An implant of 15 x 4 mm was inserted in the area of the first mandibular molar. Despite the excellent implant stability achieved, a thin central zone of the defect remained void of bone. After complete excision of soft tissue the defect was filled with an alloplastic bone substitute. Eight months later (20 months postsurgery), the implant was uncovered and the restorative procedure completed. The implant and the crown have been functioning sign and symptom free for 48 months. Marsupialization was preferred instead of enucleation due to (1) proximity of the cyst to the mandibular canal; (2) need for apicectomy of both premolars to gain good access for enucleation; (3) refusal of the patient to undergo a second surgery for bone harvesting; (4) lower probability for postoperative contamination; (5) need of small quantity of bone substitute; (6) easier extraction of the impacted second molar due to its coronal movement. The disadvantages of the treatment were the long healing period and the discomfort of the patient at the early stages of marsupialization. It was judged that the advantages outweighed the disadvantages in this case. We discuss the findings of other authors who support the conservative approach to jaw cysts in a young population, and the concerns that exist in the literature about the ability of osseoconductive graft materials to generate vital bone and achieve implant-to-bone contact.


Application of multistage continuous fermentation for production of fuel alcohol by very-high-gravity fermentation technology.
A fermentation system to test the merging of very-high-gravity (VHG) and multistage continuous culture fermentation (MCCF) technologies was constructed and evaluated for fuel ethanol production. Simulated mashes ranging from 15% to 32% w/v glucose were fermented by Saccharomyces cerevisiae and the dilution rates were adjusted for each glucose concentration to provide an effluent containing less than 0.3% w/v glucose (greater than 99% consumption of glucose). The MCCF can be operated with glucose concentrations up to 32% w/v, which indicates that the system can successfully operate under VHG conditions. With 32% w/v glucose in the medium reservoir, a maximum of 16.73% v/v ethanol was produced in the MCCF. The introduction of VHG fermentation into continuous culture technology allows an improvement in ethanol productivity while producing ethanol continuously. In comparing the viability of yeast by methylene blue and plate count procedures, the results in this work indicate that the methylene blue procedure may overestimate the proportion of dead cells in the population. Ethanol productivity (Yps) increased from the first to the last fermentor in the sequence at all glucose concentrations used. This indicated that ethanol is more effectively produced in later fermentors in the MCCF, and that the notion of a constant Yps is not a valid assumption for use in mathematical modeling of MCCFs.


Intervention approaches for rural opium users.
The rate of addiction among adults in the opium-growing areas of South East Asia and the Middle EAst varies between 3 per cent and 10 per cent. Supply-reduction efforts alone have rarely been successful and programmes aimed concurrently to reduce demand are now being initiated. Primary health care is considered a prerequisite for the success of demand-reduction programmes and includes the training of primary health care workers to assist in prevention programmes as well as in the treatment and rehabilitation of addicted persons. This supply-demand-reduction approach will require careful evaluation of its effectiveness.


Investigation on nutritional risk assessment and nutritional support status of surgical patients with colorectal cancer.
To investigate the malnutrition, the incidence of nutritional risk and the application of nutritional support for patients with colorectal cancer, so as to provide a basis for the rational clinical application of nutritional support. A total of 264 surgical patients with colorectal cancer treated/followed up from January 2016 to March 2017 in Beijing Chaoyang Hospital were selected. The nutritional risk was assessed using the Nutritional Risk Screening 2002 (NRS2002), and the nutritional risk and application of nutritional support for patients with different gender, age and clinical disease stage were analyzed; the hospitalization duration and postoperative complications were also analyzed and compared. According to NRS2002, malnutrition accounted for 6.06% and nutrition risk accounted for 79.55%. There was no statistically significant difference in the nutritional risk between patients with different gender (p=0.059), the nutritional risk of the elderly patients (≥60 years) was higher than that of the non-elderly patients (<60 years) (p<0.001), and the nutritional risk among patients with different clinical stages had no statistically significant difference (p=0.654). All patients received nutritional support; the parenteral nutrition (PN) support rate was 39.02%, while PN+enteral nutrition (EN) support rate was 60.98%, while there was no patient receiving complete EN support. There was no statistically significant difference in the incidence rates of postoperative complications between patients with and without nutritional risk (p=0.546), but there was a statistically significant difference in the hospitalization duration between patients with and without nutritional risk (p=0.019). The incidence rates of malnutrition and nutritional risk are high in patients with colorectal cancer and the incidence of nutritional risk is related to age. The application of NRS2002 in nutritional risk screening for patients with colorectal cancer can provide a reasonable and effective basis for the clinical nutritional support.


Effect of prolonged sedation with propofol on serum triglyceride and cholesterol concentrations.
We compared changes in serum lipid concentrations in ICU patients receiving a 3-day continuous infusion of propofol with those in patients receiving conventional sedation. No adverse effects were observed and the serum lipid concentrations were not significantly influenced by propofol. It is concluded that propofol might be a suitable agent for long-term sedation in the ICU, although serum lipid concentrations should be monitored throughout its administration.


Paroxetine treatment of generalized anxiety disorder.
Generalized anxiety disorder (GAD) is a prevalent and disabling anxiety disorder, conservatively believed to affect at least 5% of the general population. Cardinal symptoms of GAD include chronic and uncontrollable worry, anxiety, and tension, which result in difficulty fulfilling social, professional, and family roles. Treatment options include benzodiazepines, tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine XR. Because of the high comorbidity of GAD with other psychiatric disorders, pharmacologic therapy should possess both anxiolytic and antidepressive properties for best outcomes. The SSRIs are a good treatment option, and paroxetine is the best studied SSRI for GAD and the only SSRI to date approved by the US Food and Drug Administration for this indication. Results of randomized, controlled studies of paroxetine have demonstrated its efficacy in the short-term treatment of GAD, in achieving and sustaining full remission, and in preventing relapse. This article provides an overview of GAD and a discussion of studies of paroxetine treatment in this anxiety disorder.


The effects of surface structure mutations in Arabidopsis thaliana on the polarization of reflections from virus-infected leaves.
The way in which light is polarized when reflected from leaves can be affected by infection with plant viruses. This has the potential to influence viral transmission by insect vectors due to altered visual attractiveness of infected plants. The optical and topological properties of cuticular waxes and trichomes are important determinants of how light is polarized upon reflection. Changes in expression of genes involved in the formation of surface structures have also been reported following viral infection. This paper investigates the role of altered surface structures in virus-induced changes to polarization reflection from leaves. The percentage polarization of reflections from Arabidopsis thaliana cer5, cer6 and cer8 wax synthesis mutants, and the gl1 leaf hair mutant, was compared to those from wild-type (WT) leaves. The cer5 mutant leaves were less polarizing than WT on the adaxial and abaxial surfaces; gl1 leaves were more polarizing than WT on the adaxial surfaces. The cer6 and cer8 mutations did not significantly affect polarization reflection. The impacts of Turnip vein clearing virus (TVCV) infection on the polarization of reflected light were significantly affected by cer5 mutation, with the reflections from cer5 mutants being higher than those from WT leaves, suggesting that changes in CER5 expression following infection could influence the polarization of the reflections. There was, however, no significant effect of the gl1 mutation on polarization following TVCV infection. The cer5 and gl1 mutations did not affect the changes in polarization following Cucumber mosaic virus (CMV) infection. The accumulation of TVCV and CMV did not differ significantly between mutant and WT leaves, suggesting that altered expression of surface structure genes does not significantly affect viral titres, raising the possibility that if such regulatory changes have any adaptive value it may possibly be through impacts on viral transmission.


Extended focal radiotherapy of 30 Gy alone for intracranial synchronous bifocal germinoma: a single institute experience.
To evaluate the disease characteristics and treatment outcomes for patients with intracranial synchronous bifocal germinomas treated with extended focal irradiation alone. Between January 1996 and March 2007, seven patients (three males and four females) with intracranial synchronous bifocal germinomas treated at Taipei Veterans General Hospital were reviewed. The median age at diagnosis was 14 years (range, 11-28 years). Four patients had surgery before radiotherapy. All patients underwent extended focal irradiation encompassing the whole ventricle system with a total radiation dose of 30 Gy (2 Gy daily). No patient received scheduled systemic chemotherapy before or after radiotherapy. Disease characteristics, treatment outcomes, and the impact of lesion numbers (single vs. bifocal) on survivals were investigated. With a median follow-up time of 49 months (range, 20-66 months), the 2- and 5-year survival rates were both 100%. After treatment, all patients had good performance without recurrence. No severe complication was observed. In comparison, the overall survival (OS, p = 0.475) and the disease-free survival (DFS, p = 0.537) rates were not significantly different between bifocal- and single-lesion groups. Lesion numbers did not affect both OS and DFS. In addition, the incidence of neuraxial seeding was not higher in patients with bifocal germinomas as compared to those with single lesion. Intracranial germinomas are extremely radiosensitive. Young patients with synchronous bifocal germinomas could be successfully treated with extended focal 30-Gy radiotherapy alone. The therapeutic advantage using this regimen needs to be further evaluated with larger sample size and longer follow-up time.


Perceiving and expressing feelings through actions in relation to individual differences in empathic traits: the Action and Feelings Questionnaire (AFQ).
Empathy is usually conceived of as independent of the non-verbal behaviors which mediate its experience, though embodied cognition theory predicts that individual differences in action representation will affect empathic traits. The "Actions and Feelings Questionnaire" (AFQ) was designed to capture individual differences in self-awareness of own and others' actions, particularly those associated with feelings, which we predicted would correlate with levels of empathic traits. A pilot 30-item questionnaire included items on perceptual sensitivity to action, imitation, action imagery, and gestural and facial expression. It was completed by a sample of 278 adults (mean age 21.2 years; 189 females, 89 males) along with the 15-item Empathic Quotient (EQ) Questionnaire. Total scores on the final 18-item questionnaire showed strong internal coherence (Cronbach's alpha of 0.81) and test-retest reliability (ICC=0.88), marked effect of sex and highly significant correlation with EQ. The questionnaire was administered to participants in an fMRI study investigating the neural correlates of facial imitation. Total AFQ score correlated with activity in somatosensory cortex, insula, anterior cingulate, and visual cortex. The AFQ shows promise as a brief and simple self-report measure sensitive to variability in the self-awareness of actions associated with feelings. It suggests that much of the variability of empathic traits in typical populations is accounted for by variance in this capacity. We suggest that being more empathic really is about being "touchy-feely," and this questionnaire provides a novel measure of action-based empathy.


Inhibition of apoB secretion from HepG2 cells by insulin is amplified by naringenin, independent of the insulin receptor.
Hepatic overproduction of apolipoprotein B (apoB)-containing lipoproteins is characteristic of the dyslipidemia associated with insulin resistance. Recently, we demonstrated that the flavonoid naringenin, like insulin, decreased apoB secretion from HepG2 cells by activation of both the phosphoinositide-3-kinase (PI3-K) pathway and the mitogen-activated protein kinase/extracellular-regulated kinase (MAPK(erk)) pathway. In the present study, we determined whether naringenin-induced signaling required the insulin receptor (IR) and sensitized the cell to the effects of insulin, and whether the kinetics of apoB assembly and secretion in cells exposed to naringenin were similar to those of insulin. Immunoblot analysis revealed that insulin stimulated maximal phosphorylation of IR and IR substrate-1 after 10 min, whereas naringenin did not affect either at any time point up to 60 min. The combination of naringenin and submaximal concentrations of insulin potentiated extracellular-regulated kinase 1/2 activation and enhanced upregulation of the LDL receptor, downregulation of microsomal triglyceride transfer protein expression, and inhibition of apoB-100 secretion. Multicompartmental modeling of apoB pulse-chase studies revealed that attenuation of secreted radiolabeled apoB in naringenin- or insulin-treated cells was similar under lipoprotein-deficient or oleate-stimulated conditions. Naringenin and insulin both stimulated intracellular apoB degradation via a kinetically defined rapid pathway. Therefore, naringenin, like insulin, inhibits apoB secretion through activation of both PI3-K and MAPK(erk) signaling, resulting in similar kinetics of apoB secretion. However, the mechanism for naringenin-induced signaling is independent of the IR. Naringenin represents a possible strategy for reduction of hepatic apoB secretion, particularly in the setting of insulin resistance.


Electrical property of Mo-doped VO2 nanowire array film by melting-quenching sol-gel method.
Mo-doped VO(2) nanowire array film with good thermochromic properties was prepared by melting-quenching followed by heat treatment in a vacuum. The formation of the new microstructure is related to the cleavage of the oxide lamella along (001) and (100) plane with large interplanar spacing. Mo doping results in the loss of V(4+)-V(4+) pairs and destabilizes the semiconductor phase and consequently lowers the semiconductor-to-metal transition temperature T(c) from 64 to 42 degrees C. Because of enhancement of the electron concentration due to the presence of Mo donors, the Fermi level shifts toward the conduction band, resulting in the decrease of activation energy E(a), hence, temperature coefficient of resistance.


Electrocatalytic reactions mediated by N,N,N',N'-Tetraalkyl-1,4-phenylenediamine redox liquid microdroplet-modified electrodes: chemical and photochemical reactions In, and At the surface of, femtoliter droplets.
The electro-oxidation of electrolytically unsupported ensembles of N,N-diethyl-N',N'-dialkyl-para-phenylenediamine (DEDRPD, R = n-butyl, n-hexyl, and n-heptyl) redox liquid femtoliter volume droplets immobilized on a basal plane pyrolytic graphite electrode is reported in the presence of aqueous electrolytes. Electron transfer at these redox liquid modified electrodes is initiated at the microdroplet-electrode-electrolyte three-phase boundary. Dependent on both the lipophilicity of the redox oil and that of the aqueous electrolyte, ion uptake into or expulsion from the organic deposits is induced electrolytically. In the case of hydrophobic electrolytes, redox-active ionic liquids are synthesized, which are shown to catalyze the oxidation of l-ascorbic acid over the surface of the droplets. In contrast, the photoelectrochemical reduction of the anaesthetic reagent halothane proceeds within the droplet deposits and is mediated by the ionic liquid precursor (the DEDRPD oil).


Inter-generation comparison of type-2 diabetes in 73 Indian families.
To study type 2 diabetics in 2 generations in the same family and to see if there are any significant differences in their presentations. The study also focused on the non-diabetic siblings to see if there were any differences between them. Criteria for inclusion: 1. Proband case should have a parent who is a diabetic, 2. Proband case should have at least one sibling who is not diabetic. Entire families of such cases fulfilling the above criteria were included in the study. A detailed questionnaire was filled. This was followed by an examination of all anthropometric measurements like height, weight, waist circumference, hip circumference and blood pressure. Venous blood samples for glucose measurement (fasting and post prandial), HbA1c, renal profile, lipid profile and insulin levels were collected. Urine sample was collected in appropriate containers for microalbuminuria, albumin/creatinine ratio. The study included 73 families, with a total of 307 members (159 male and 148 female). 92 were from 1st generation and 215 from 2nd generation. Of these 182 were diabetics, 81 from 1st generation and 151 from 2nd generation (95 males and 87 females). 125 were non diabetics, 9 from 1st generation and 116 from the 2nd generation (64 males and 61 females). The mean age of onset of diabetes in 1st generation was 55.95 years (SD +/- 9.98) and in 2nd generation was 38.4 years (SD +/- 9.2) (p<0.0001). Body mass index (BMI), waist circumference, Wasist-hip ratio (W/H ratio) and triglycerides, HDL and blood pressure individually did not show any significant differences between the diabetics in both generations. The incidence of metabolic syndrome as per ATPIII criteria was 75.9 % among the 1st generation diabetics. There were only 9 non-diabetics in the first generation and this number was small to derive any statistical significance. Comparison between diabetics and non diabetics in the 2nd generation showed that the incidence of metabolic syndrome as per ATPIII criteria was significantly higher among the diabetics at 62.63% as against 28.45% in the non diabetics. BMI, W/H ratio and lipid profile individually did not show any significant differences between the diabetics and non diabetics. This study shows that the age of onset of diabetes is much earlier in the present generation being 38.4 years (SD +/- 9.2), as compared to 55.95 years (SD +/- 9.98) in the previous generation. There were no other significant differences between the two generations. In the present generation the incidence of metabolic syndrome as per ATPIII criteria was a significant risk factor for the development of diabetes. 62.63% of the diabetic siblings had metabolic syndrome as compared to 28.45% in the nondiabetic siblings. There were no other significant parameters for early detection of diabetes in this group.


Iron-Catalyzed Acyl Migration of Tertiary α-Azidyl Ketones: Synthetic Approach toward Enamides and Isoquinolones.
This paper reports that tertiary α-azidyl phenyl ketones can be transformed into enamides by treatment with FeBr2 at elevated temperature in DMF. The reaction proceeds via 1,2-benzoyl migration from α-carbon to the nitrogen atom, accompanied by expulsion of a nitrogen molecule. This protocol is suitable for the synthesis of N-(cyclopent-1-en-1-yl)benzamides, N-(cyclohex-1-en-1-yl)benzamides, and N-benzoyl-α-methyl enamines and provides a convenient approach toward isoquinolones.


[Physical development in patients with acute lymphoblastic leukemia in childhood].
Acute lymphoblastic leukaemia (ALL) is one of the readily treatable neoplastic diseases of childhood. One of the late sequelae of treatment can be impaired growth. The authors followed up therefore a group of 63 patients where during childhood a diagnosis of ALL was made. The investigated group was treated according to two fundamental protocols--according to Pinkel's protocol and according to BMF protocols. All patients treated according to Pinkel's protocol had, as part of prevention of leukaemia of the CNS, radiotherapy of the skull, patients treated according to the BMF protocol only when the risk factor was higher than 0.8. The authors investigated in their patients the height and proportionality after termination of all antileukaemic therapy. They found that the height of children, adolescents and adults who suffered from ALL during childhood is average or less. A tendency towards obesity is typical. The authors did not observe a correlation with the total cumulative doses of cytostatics nor a marked correlation with radiotherapy. Impaired growth was more frequent when ALL was diagnosed before the age of 3 years and where the interval after completed therapy was shorter.


Phage dUTPases control transfer of virulence genes by a proto-oncogenic G protein-like mechanism.
dUTPases (Duts) have emerged as promising regulatory molecules controlling relevant cellular processes. However, the mechanism underlying this regulatory function remains enigmatic. Using staphylococcal pathogenicity island (SaPI) repression as a model, we report here that phage Duts induce the transfer of SaPI-encoded virulence factors by switching between active (dUTP-bound) and inactive (apo state) conformations, a conversion catalyzed by their intrinsic dUTPase activity. Crystallographic and mutagenic analyses demonstrate that binding to dUTP reorders the C-terminal motif V of the phage-encoded Duts, rendering these proteins into the active conformation required for SaPI derepression. By contrast, the conversion to the apo state conformation by hydrolysis of the bound dUTP generates a protein that is unable to induce the SaPI cycle. Because none of the requirements involving Duts in SaPI transfer are exclusive to the phage-encoded proteins, we propose that Duts are widespread cellular regulators acting in a manner analogous to the eukaryotic G proteins.


Effect of latanoprost on hair growth in the bald scalp of the stump-tailed macacque: a pilot study.
Latanoprost, a selective FP prostanoid receptor agonist used in the treatment of glaucoma, has a hypertrichotic side effect. Using the macaque model of androgenetic alopecia, we examined the effect of latanoprost on hair growth. Eight monkeys were divided into 2 groups; one group received a daily topical application of 50 microg/ml of latanoprost for 5 months; a control group had a daily application of vehicle. For an additional 3 months, 2 monkeys from each group were given 500 microg/ml latanoprost, while the remaining monkeys continued with the previous treatment. Hair growth was evaluated by monthly photographs and phototricho-graphic analysis. Fifty microg/ml of latanoprost caused minimal hair growth. Latanoprost at 500 microg/ml induced moderate to marked hair regrowth with 5-10% conversion of vellus hairs to intermediary or terminal hairs. The vehicle group showed no effect. Further evaluation of latanoprost as an agent for treatment of human androgenetic alopecia is indicated.


["The phlebotomist" - venous punction and venous access obtaining in the department of oncology].
The protection of the veins in patients with malignancies is of high importance (regarding both blood taking and the drug administration). In order to prevent any unnecessary injury, every phlebotomy needs to have a sophisticated indication and requires skilled hands and adequate mentality. For the administration of cytostatic treatment, insertion of cannula is necessary, in most of the cases through a peripheral vein. Recently with more successful treatment possibilities, patients undergo many subsequent types of treatment. Thus, more examinations and diagnostic procedures (e.g. blood taking, radiologic examinations) are needed. Therefore, the need for central venous catheter or Porth-a-Cath device is increasing. Our report demonstrates general guidelines of blood taking and our everyday practice.


[Polypoid lesions of the gallbladder wall].
Modern sonography has led to an increased appraisal of the therapeutic consequences in cases of polypoid lesions of the gallbladder wall. In 30 patients it was attempted to differentiate between cholesterol polyps and polypoid lesions suspect for malignancy. Histologic results and data in the literature induce us to recommend cholecystectomy in solitary lesions of more than 5 mm, combined occurrence with gallstones and in patients beyond the 60th year of life.


Phospholipids chiral at phosphorus. Synthesis of chiral phosphatidylcholine and stereochemistry of phospholipase D.
Chirally labeled 1,2-dipalmitoyl-sn-glycero-3-phosphocholines (DPPC) with known configuration were synthesized by N-methylation of chirally labeled 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE). Transphosphatidylation of (RP)- and (SP)-[18O]DPPC catalyzed by phospholipase D from cabbage gave (RP)- and (SP)-[18O]DPPE, respectively, as indicated by 31P nuclear magnetic resonance (NMR) analysis of [18O]DPPE. Therefore, phospholipase D catalyzes transphosphatidylation with overall retention of configuration at phosphorus. The steric course of hydrolysis of DPPC catalyzed by the same enzyme was elucidated by the following procedures. Hydrolysis of (RP)-[17O, 18O]DPPC by phospholipase D gave 1,2-dipalmitoyl-sn-glycero-3-[ 16O , 17O, 18O]phosphate ( [ 16O , 17O, 18O] DPPA ) with unknown configuration. The latter compound was then converted to 1-[ 16O , 17O, 18O]phospho-(R)-propane-1,2-diol by a procedure involving no P-O bond cleavage [ Bruzik , K., & Tsai, M.-D. (1984) J. Am. Chem. Soc. 106, 747-754]. The configuration of the phosphopropane -1,2-diol was determined as RP by 31P NMR analysis following ring closure and methylation [ Buchwald , S. L., & Knowles, J. R. (1980) J. Am. Chem. Soc. 102, 6601-6603]. The results indicated that hydrolysis of DPPC catalyzed by phospholipase D also proceeds with retention of configuration at phosphorus. Our results therefore support a two-step mechanism involving a phosphatidyl-enzyme intermediate in the reactions catalyzed by phospholipase D from cabbage.


Cell-mediated reactivity in dermatophytosis: differences in skin responses to purified trichophytin in tinea pedis and tinea cruris.
Cell-mediated immune responses were measured in 91 patients with dermatophytosis by means of delayed-type skin hypersensitivity to a purified trichophytin preparation (ethylene glycol method) and to tuberculin (purified protein derivative, PPD). The findings indicate that dermatophytes differ in their sensitizing capacity as measured by trichophytin skin sensitivity. Trichophyton mentagrophytes appeared to be a potent sensitizer compared with Trichophyton rubrum (p < 0.01), whereas Epidermophyton floccosum appeared as a moderate sensitizer. The localization of infection also affected the cell-mediated response to trichophytin, i.e. the frequency of reactions was 44% in tinea cruris and 33% in tinea pedis, while tinea pedis with nail infections elicited delayed-type reactivity in 60% of cases. On the basis of the significant difference (p < 0.001) in cell-mediated reactivity between chronically and non-chronically infected subjects as measured with trichophytin, it is concluded that the cell-mediated response is of importance for the development of host resistance to dermatophytic infections. This study provides further evidenced in support of the view that a partial defect in the cell-mediated system may be responsible for establishment of chronic dermatophytosis.


Interstitial telomere-like repeats in the Arabidopsis thaliana genome.
Eukaryotic chromosomal ends are protected by telomeres, which are thought to play an important role in ensuring the complete replication of chromosomes. On the other hand, non-functional telomere-like repeats in the interchromosomal regions (interstitial telomeric repeats; ITRs) have been reported in several eukaryotes. In this study, we identified eight ITRs in the Arabidopsis thaliana genome, each consisting of complete and degenerate 300- to 1200-bp sequences. The ITRs were grouped into three classes (class IA-B, class II, and class IIIA-E) based on the degeneracy of the telomeric repeats in ITRs. The telomeric repeats of the two ITRs in class I were conserved for the most part, whereas the single ITR in class II, and the five ITRs in class III were relatively degenerated. In addition, degenerate ITRs were surrounded by common sequences that shared 70-100% homology to each other; these are named ITR-adjacent sequences (IAS). Although the genomic regions around ITRs in class I lacked IAS, those around ITRs in class II contained IAS (IASa), and those around five ITRs in class III had nine types of IAS (IASb, c, d, e, f, g, h, i, and j). Ten IAS types in classes II and III showed no significant homology to each other. The chromosomal locations of ITRs and IAS were not category-related, but most of them were adjacent to, or part of, a centromere. These results show that the A. thaliana genome has undergone chromosomal rearrangements, such as end-fusions and segmental duplications.


D. pteronyssinus-tyrosine adsorbate: biological and clinical properties.
Adsorption of D. pteronyssinus on tyrosine gives a depot formulation with retained immunogenicity. Preliminary clinical evaluation of this material showed improvement in the majority of allergic subjects after receipt of the initial six doses, improvement being continued during subsequent maintenance therapy.


Quantification-based mass spectrometry imaging of proteins by parafilm assisted microdissection.
MALDI mass spectrometry imaging (MALDI-MSI) was presented as a good strategy to highlight regions presenting specific phenotypes based on molecular content. The proteins present in the different areas can be identified by MALDI MSI; however, the number of protein identifications remains low in comparison with classical MS-based proteomics approaches. To overcome this, a new strategy, involving the microdissection of tissue sections mounted on parafilm M-covered glass slides, is presented. Extraction and fractionation of proteins from a specific region of interest were investigated, leading to the identification of more than 1000 proteins from each microdissected piece. The strength of this cheap technique lies in the facile excision of millimeter-sized portions from the tissue allowing for the identification of proteins from cells of a specific phenotype obtained from the MALDI MS imaging-based molecular classification using hierarchical clustering. This approach can be extended to whole tissue sections in order to generate images of the section based on label-free quantification obtained from identification data. As a proof of concept, we have studied a tissue mounted on a parafilm M-covered glass slide, cut it into regular pieces, and submitted each piece to identification and quantification according to the developed parafilm-assisted microdissection (PAM) method. Images were then reconstructed by relative quantification of identified proteins based on spectral counting of the peptides analyzed by nanoLC-MS and MS/MS. This strategy of quantification-based MSI offers new possibilities for mapping a large number of high and low abundance proteins.


Characterization of a new dual-targeting fully human antibody with potent antitumor activity against nasopharyngeal carcinoma.
Despite the effectiveness of the anti-EGFR chimeric antibody (mAb), cetuximab, in treating nasopharyngeal carcinoma (NPC), its efficacy remains variable and often modest. In this study, a full human dual targeted anti-EGFR/HER3 antibody, CA1182, was generated from phage display library. CA1182 was as effective as cetuximab or trastuzumab in inhabiting phosphorylation of EGFR or HER2, but it exhibited as much more potent than cetuximab or trastuzumab. Moreover, our studies showed that CA1182 was significantly more effective than cetuximab in prolonging the survival of severe combined immune deficient mice bearing human NPC, suggesting that it might be a promising therapeutic agent for NPC.


Extramedullary compared with intramedullary implants for intertrochanteric hip fractures: thirty-day outcomes of 4432 procedures from the ACS NSQIP database.
For more than thirty-five years, the sliding hip screw, an extramedullary implant, has been the standard treatment for the stabilization of intertrochanteric fractures. Over the last decade, intramedullary implants have replaced extramedullary implants as the most commonly used type of implant in the United States for the treatment of this condition, without strong evidence of superior outcomes. We conducted a retrospective cohort study with use of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database. Patients seventy years of age or older who had sustained an intertrochanteric fracture treated with extramedullary or intramedullary implant during 2009 to 2012 were identified. General surgical outcomes were compared between implant types, with adjustment for demographic data and comorbidities. A total of 4432 patients were identified; 1612 (36.4%) were treated with an extramedullary implant, and 2820 (63.6%) with an intramedullary implant. The rates of the composite outcomes "serious adverse events" and "any adverse events" did not differ by implant type. The mean postoperative length of stay was shorter for patients treated with an intramedullary implant compared with those treated with an extramedullary implant (5.4 compared with 6.5 days; p < 0.001). Operation time, operating room time, and the rate of hospital readmission did not differ by implant type. These results reinforce the results of previous randomized trials, demonstrating little difference in rates of general surgical adverse events between implant types. The present study presents an important departure from previous trials in its finding that patients treated with intramedullary implants have, on average, a shorter postoperative length of stay (by 1.1 days). The finding may negate the perceived excess cost associated with intramedullary treatment. Limitations regarding the ACS NSQIP database include a lack of detail regarding fracture subtype, outcomes beyond thirty days, and orthopaedic-specific outcomes.


Hybrid Corpectomy and Disc Arthroplasty for Cervical Spondylotic Myelopathy Caused by Ossification of Posterior Longitudinal Ligament and Disc Herniation.
The combination of anterior cervical discectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF) has been demonstrated to be effective for multilevel cervical spondylotic myelopathy (CSM); however, the combination of ACCF and cervical disc arthroplasty (CDA) for 3-level CSM has never been addressed. Consecutive patients (>18 years of age) with CSM caused by segmental ossification of posterior longitudinal ligament (OPLL) and degenerative disc disease (DDD) were reviewed. Inclusion criteria were patients who underwent hybrid ACCF and CDA surgery for symptomatic 3-level CSM with OPLL and DDD. Medical and radiologic records were reviewed retrospectively. A total of 15 patients were analyzed with a mean follow-up of 18.1 ± 7.42 months. Every patient had hybrid surgery composed of 1-level ACCF (for segmental-type OPLL causing spinal stenosis) and 1-level CDA at the adjacent level (for DDD causing stenosis). All clinical outcomes, including visual analogue scale of neck and arm pain, Neck Disability Index, Japanese Orthopedic Association scores, and Nurick scores of myelopathy, demonstrated significant improvement at 12 months after surgery. All patients (100%) achieved arthrodesis for the ACCF (instrumented) and preserved mobility for CDA (preoperation 6.2 ± 3.81° vs. postoperation 7.0 ± 4.18°; P = 0.579). For patients with multilevel CSM caused by segmental OPLL and DDD, the hybrid surgery of ACCF and CDA demonstrated satisfactory clinical and radiologic outcomes. Moreover, although located next to each other, the instrumented ACCF construct and CDA still achieved solid arthrodesis and preserved mobility, respectively. Therefore, hybrid surgery may be a reasonable option for the management of CSM with OPLL.


Delivery of membrane proteins into small and giant unilamellar vesicles by charge-mediated fusion.
One of the current challenges in synthetic biology is the production of stable membrane mimetic systems and the insertion of components in these systems. Here, we employ fusion of oppositely charged liposomes to deliver separately reconstituted membrane proteins into a common lipid bilayer. After a systematic evaluation of different lipid compositions by lipid mixing and size distribution analysis, suitable conditions were further investigated for proteoliposome fusion. With this technique, we functionally coreconstituted bo3 oxidase and ATP synthase from Escherichia coli into unilamellar liposomes ranging from 100 nm to 50 μm in size. The presented method is a simple and versatile tool for oriented membrane protein reconstitution to produce biomimetic systems with increased complexity.


Role of IL-10 and TGF-β1 in local immunosuppression in HPV-associated cervical neoplasia.
Cervical cancer is a worldwide disease that constitutes a significant public health problem, especially in developing countries, not only due to its high incidence but also because the most affected population comprises women who belong to marginalized socio-economic classes. Clinical and molecular research has identified immunological impairment in squamous intraepithelial cervical lesions and cervical cancer patients. Human Papillomavirus (HPV) has several mechanisms for avoiding the immune system: it down-regulates the expression of interferon and upregulates interleukin (IL)-10 and transforming growth factor (TGF)-β1 to produce a local immunosuppressive environment, which, along with altered tumor surface antigens, forms an immunosuppressive network that inhibits the antitumor immune response. In this review we analyzed the available data on several deregulated cellular immune functions in patients with NIC I, NIC II and NIC III and cervical cancer. The effects of immunosuppressive cytokines on innate immune response, T-cell activation and cellular factors that promote tumor cell proliferation in cervical cancer patients are summarized. We discuss the functional consequences of HPV E2, E6, and E7 protein interactions with IL-10 and TGF-β1 promoters in the induction of these cytokines and postulate its effect on the cellular immune response in squamous intraepithelial cervical lesions and cervical cancer patients. This review provides a comprehensive picture of the immunological functions of IL-10 and TGF-β1 in response to HPV in humans.


Peer Victimization and Unhealthy Weight Control Behaviors-the Role of Intersecting Identities among New York City Youth.
We investigated the intersection of sexual minority, gender, and Hispanic identities, and their interaction with peer victimization in predicting unhealthy weight control behaviors (UWCB) among New York City (NYC) youths. Using logistic regression with data from the 2011 NYC Youth Risk Behavior Survey, we examined the association of sexual identity, gender, ethnicity, and peer victimization (dating violence, bullying at school, electronic bullying) in predicting UWCB. Sexual minority youths, dating violence victims, and youths bullied at school had 1.97, 3.32, and 1.74 times higher odds of UWCB than their counterparts, respectively (P < 0.001). The three-way interaction terms between (i) dating violence, gender, and sexual identity and (ii) electronic bullying, gender, and sexual identity were statistically significant. The effect of dating violence on unhealthy weight control practices was strongest among sexual minority males (OR = 4.9), and the effect of electronic bullying on unhealthy weight control practices was strongest among non-sexual minority males (OR = 2.9). Sexual minority and gender identities interact with peer victimization in predicting unhealthy weight control practices among NYC youths. To limit the prevalence and effect of dating violence and electronic bullying among youths, interventions should consider that an individual's experiences are based on multiple identities that can be linked to more than one ground of discrimination.


[On the origins of university psychology in France (1870-1900): intellectual stakes, political context, networks and strategies].
The university study of psychology originated in France in the 1880's. The first practitioners conceived of it as psychophysiology, a natural science, as opposed to an aspect of spiritual philosophy, which needed to be understood in a specific political context. This paper analyses this seminal period through the militant activity of its main architect, Theodule Ribot (1839-1916). It particularly questions the orientations of the Revue philosophique, founded in 1876, which proved a rally-point for the young philosophers and physicians who derived from Ribot their alliance strategy within the medical milieu. The inquiry is continued to the turn of the century, when psychology became firmly institutionalized.


Bioremediation of chromium contaminated environments.
Bioremediation is the most promising and cost effective technology widely used nowadays to clean up both soils and wastewaters containing organic or inorganic contaminants. Discharge of chromium containing wastes has led to destruction of many agricultural lands and water bodies. Utilisation of chromium(Cr) reducing microbes and their products has enhanced the efficiency of the process of detoxification of Cr(VI) to Cr(III). This review focuses mainly on the current technologies prevalent for remediation like natural attenuation, anaerobic packed bed bioreactors (using live cells, Cr(VI) reductases or their byproducts) and use of engineered microorganisms. Treatment of wastewaters by biosorption or using biofilms and immobilized microbial cells are also discussed.


Keratoameloblastoma: Report of a rare variant with review of literature.
Ameloblastoma has intrigued clinicians as well as pathologists due to its diverse clinical behavior and histomorphologic presentations. Keratoameloblastoma is a rare histologic sub type, characterized by extensive keratin formation within ameloblastic epithelium, with only a handful number of cases described in the literature. Here, we report a case of this uncommon sub type of ameloblastoma in a young female patient presenting as an extensive lesion in mandibular ramus area. The radiological and fine needle aspiration findings suggested of a keratinizing cystic lesion and incisional biopsy showed features of ameloblastoma. Patient underwent segmental mandibulectomy and histological examination of excisional specimen revealed features of ameloblastoma with abundant keratinization leading to a diagnosis of keratoameloblastoma. The diagnostic pitfalls related with the lesion have been discussed along with a short review of the literature.


Virtual unenhanced images derived from dual-energy computed tomography for assessing bone mineral density and detecting osteoporosis.
The early detection and treatment of osteoporosis can help prevent osteoporosis-related fractures, especially in patients who undergo enhanced computed tomography (CT) scans for disease diagnosis or evaluation of treatment outcomes. Although Hounsfield unit (HU) measurement of the vertebral body has been shown to have a strong positive correlation with bone mineral density (BMD), the contrast media will impact the CT value of the vertebral body and decrease the accuracy. This study is aimed to examine the distinctions in vertebral body CT attenuation measurement on true unenhanced (TUE) and virtual unenhanced (VUE) images generated from triphasic enhanced dual-energy CT (DECT) scans and to determine the feasibility of assessing BMD and detecting osteoporosis on VUE images as compared to quantitative CT (QCT). A total of 235 patients underwent abdominal CT examinations that included unenhanced (with 120 kVp and Smart mA) and triphasic enhanced DECT scans. The BMD and CT attenuation values of the L1-L2 vertebrae were measured on TUE and VUE images reconstructed from the triphasic enhanced CT. The differences and associations between TUE and VUE generated from triphasic enhanced CT were analyzed. The diagnostic performances of HU measurements obtained from TUE and VUE images were evaluated using receiver operating characteristic curve. The BMD and HU measurements of the vertebrae showed good interobserver repeatability on both TUE and VUE images (all intercorrelation coefficients >0.92). The CT attenuation values of L1 and L2 and their average value showed no statistically significant difference among the triphasic VUE images (F=0.121, F=0.061, F=0.090; all P values >0.05) but were significantly lower than those obtained from the TUE images. HU measurements in both the TUE and triphasic VUE images, along with the reference BMD derived from QCT, demonstrated a strong positive correlation (rTUE =0.981, rVUEa =0.966, rVUEv =0.962, rVUEd =0.964; all P values <0.05), with excellent diagnostic performance for the diagnoses of osteoporosis and osteopenia (all areas under curve >0.95). The Bland-Altman scatter plot exhibited good agreement, as the deviations between the reference BMD and the calculated BMD were evenly distributed around 0. Although the attenuation values of the vertebrae on the VUE images were underestimated compared to those on the TUE images, the HU measurement on VUE image was effective in assessing BMD and detecting osteoporosis and osteopenia with good diagnostic performance.


Identification of two novel mutations in the RET proto-oncogene in the same family.
Activating germline mutations of the RET gene cause multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma (FMTC), conditions that are inherited in an autosomal dominant manner. In addition, somatic RET mutations have been identified in a variable proportion (about 30-70%) of sporadic (nonfamilial) MTC cases. We describe a Greek family with two novel likely pathogenic sequence variants of the RET gene. The first is a C to T transition at position 2458 (c.2458C>T) that causes an arginine to cysteine substitution (p.R820C) in exon 14 in the intracellular region of the kinase. This sequence variant was identified in an apparently healthy woman who had a recently deceased sister with confirmed aggressive MTC (age of onset 37 years). To assess the pathogenicity of this novel missense sequence variant, screening was performed on all available relatives: her two sons, the mother, and a second sister, including an MTC tumor sample from the deceased sister of the proband. At the time of the investigation, no clinical symptoms suggestive of multiple endocrine neoplasia type 2 or MTC were present in any of the individuals screened. The c.2458C>T transition was found in one son, the living sister, and the mother. Interestingly, it was not present in the tumor sample from the deceased sister. Instead, an in-frame deletion of 54 nt in exon 10 resulting in a protein missing 18 amino acids from I590 to G608 (c.1766_1819del 54) was found. Both genetic alterations were present in heterozygous state. These data suggest that the novel in-frame deletion was the disease-causing mutation in the deceased sister. The effect of the 2458C>T mutation on the activity of the kinase is under investigation.


Rufinamide-Loaded Chitosan Nanoparticles in Xyloglucan-Based Thermoresponsive In Situ Gel for Direct Nose to Brain Delivery.
In 2004, the US FDA approved Rufinamide, an anti-epileptic drug under the brand name Banzel®. In 2015, Banzel® received approval for its use in pediatric patients (ages 1-4 years). Rufinamide shows low oral bioavailability due to a low dissolution rate resulting in less of the drug reaching the brain. This has led to the high dose and dosing frequency of Rufinamide. In this work, using the principle of design of experiments (DoE), we have formulated Rufinamide-loaded chitosan nanoparticles and suspended them in a solution of a thermoresponsive polymer-tamarind seed xyloglucan to form a nasal in situ gel for direct nose to brain delivery of Rufinamide. The nanoparticles were characterized for particle size, entrapment efficiency, zeta potential, and physical stability. The in situ gel formulations were characterized for rheological properties, stability, and in vivo plasma and brain pharmacokinetics. Pharmacokinetic parameters were computed for aqueous suspension of nanoparticles and in situ gelling formulation for nanoparticles and compared with the pharmacokinetic parameters of an aqueous suspension of plain Rufinamide. The percentage of direct transport efficiency (% DTE) and direct transport percentage (%DTP) values were calculated for all the formulations. The optimized nanoparticle formulation showed a size of 180 ± 1.5 nm, a zeta potential of 38.3 ± 1.5 mV, entrapment efficiency of 75 ± 2.0%, and drug loading of 11 ± 0.3%. The in situ gelling formulation of nanoparticles showed a solution to the gel transition temperature of 32°C. The %DTE values for aqueous suspension of nanoparticles and in situ gelling formulation for nanoparticles were 988.5 and 1177.3 and the %DTP values were 86.06 and 91.5 respectively.