Objective assessments of lip movement can be beneficial in many disciplines including visual speech recognition, for surgical outcome assessment in patients with cleft lip and for the rehabilitation of patients with facial nerve impairments. The aim of this study was to develop an outcome measure for lip shape during speech using statistical shape analysis techniques. Lip movements during speech were captured from a sample of adult subjects considered as average using a three-dimensional motion capture system. Geometric Morphometrics was employed to extract three-dimensional coordinate data for lip shape during four spoken words decomposed into seven visemes (which included the resting lip shape). Canonical variate analysis was carried out in an attempt to statistically discriminate the seven visemes. The results showed that the second canonical variate discriminated the resting lip shape from articulation of the utterances and accounted for 17.2% of the total variance of the model. The first canonical variate was significant in discriminating between the utterances and accounted for 72.8% of the total variance of the model. The outcome measure was created using the 95% confidence intervals of the canonical variate scores for each subject plotted as ellipses for each viseme. The method and outcome model is proposed as reference to compare lip movement during speech in similar population groups.
In MPTP animal models of Parkinson’s disease (PD), caffeine protects neurons by blocking the adenosine receptor A2A (ADORA2A). Caffeine is primarily metabolized by cytochrome P450 1A2 (CYP1A2). Our objective was to examine whether ADORA2A and CYP1A2 polymorphisms are associated with PD risk or modify the caffeine-PD association.
Parkinson’s Epidemiology and Genetic Associations Studies in the United States (PEGASUS) included five population-based case-control studies. One laboratory genotyped four ADORA2A and three CYP1A2 polymorphisms in 1325 PD cases and 1735 age- and sex-matched controls. Information regarding caffeine (coffee) consumption and other lifestyle factors came from structured in-person or telephone interviews. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression.
Two ADORA2A polymorphisms were inversely associated with PD risk – rs71651683, a 5’ variant (adjusted allelic OR= 0.51, 95% CI 0.33–0.80, permutation-adjusted p=0.015) and rs5996696, a promoter region variant (adjusted OR for AC and CC genotypes compared with the AA wildtype genotype were 0.76 (95% CI 0.57–1.02) and 0.37 (95% CI 0.13–1.01), respectively (permutation-adjusted p for trend=0.04). CYP1A2 polymorphisms were not associated with PD risk; however, the coffee-PD association was strongest among subjects homozygous for either variant allele rs762551 (pinteraction=0.05) or rs2470890 (pinteraction=0.04).
In this consortium study, two ADORA2A polymorphisms were inversely associated with PD risk, but there was weak evidence of interaction with coffee consumption. In contrast, the coffee-PD association was strongest among slow metabolizers of caffeine who were homozygous carriers of the CYP1A2 polymorphisms.
Parkinson's disease; caffeine; adenosine receptor A2A; polymorphisms; CYP1A2; case-control; epidemiology
The goal of this study is to demonstrate a practical magnetic resonance imaging technique for quantifying a wide range of hepatic iron concentration (HIC) for hematologic oncology patients with transfusion iron overload in a routine clinical setting. To cover a wide range of T2* values from hematologic patients, we used a dual-acquisition method with two clinically available acquisition protocols on a 1.5T MRI scanner with different ΔTEs to acquire data in two breath-holds. An in-house image postprocessing software tool was developed to generate T2*, iron maps, and water and fat images, when fat is presented in the liver. The resulting iron maps in DICOM format are transferred to the institutional electronic medical record system for review by radiologists. The measured liver T2* values for 28 patients ranged from 0.56 ± 0.13 to 25.0 ± 2.1 milliseconds. These T2* values corresponded to HIC values ranging from 1.2 ± 0.1 mg/g to 45.0 ± 10.0 mg/g (dry weight). A moderate correlation between overall serum ferritin levels and R2* was found with a correlation coefficient of 0.83. Repeated phantom scans confirmed that the precision of this method is better than 4% for T2* measurements. The dual- acquisition method also improved the ability to quantify HIC of the patients with hepatic steatosis.
This study quantified the antibiotic release kinetics and subsequent bactericidal efficacy of rifampicin (RIF) against Gram-positive and Gram-negative bacteria under in vitro static conditions. Antibiotic-loaded scaffolds were fabricated by electrospinning poly(caprolactone) (PCL) with 10% or 20% (w/w) RIF. Scaffold fiber diameter and RIF loading were characterized, and RIF release kinetics were measured. RIF-releasing and RIF-free scaffolds were inoculated with Pseudomonas aeruginosa and Staphylococcus epidermidis, and the suspended concentration live and dead bacteria were determined by fluorescent microscopy. Adherent bacteria and biofilm formation were examined using scanning electron microscopy. Mean fiber diameters were 557 ± 399 nm for RIF-free, 402 ± 225 nm for 10% RIF, and 665 ± 402 nm for 20% RIF scaffolds. RIF release kinetics exhibited a short-burst release during the first hour, followed by a 7 h, zero-order release during which both RIF scaffolds released ~50% of their initial RIF mass loading. P. aeruginosa and S. epidermidis suspended cell populations proliferated in accordance with logarithmic growth models when exposed to control scaffolds; however both RIF-containing scaffolds completely inhibited bacterial growth in suspension and, subsequently, prevented biofilm formation within the scaffolds through the first 6 h.
The idea from human societies that self-interest can lead to a breakdown of cooperation at the group level is sometimes termed the public goods dilemma. We tested this idea in the opportunistic bacterial pathogen, Pseudomonas aeruginosa, by examining the influence of putative cheats that do not cooperate via cell-to-cell signalling (quorum-sensing, QS). We found that: (i) QS cheating occurs in biofilm populations owing to exploitation of QS-regulated public goods; (ii) the thickness and density of biofilms was reduced by the presence of non-cooperative cheats; (iii) population growth was reduced by the presence of cheats, and this reduction was greater in biofilms than in planktonic populations; (iv) the susceptibility of biofilms to antibiotics was increased by the presence of cheats; and (v) coercing cooperator cells to increase their level of cooperation decreases the extent to which the presence of cheats reduces population productivity. Our results provide clear support that conflict over public goods reduces population fitness in bacterial biofilms, and that this effect is greater than in planktonic populations. Finally, we discuss the clinical implications that arise from altering the susceptibility to antibiotics.
quorum-sensing; biofilms; public goods; spatial structure; cooperation; cheating
To examine genetic associations of polymorphisms in the dopamine receptor D2 (DRD2) and D3 (DRD3) genes with risk of Parkinson’s disease (PD).
The study included 1325 newly diagnosed patients with PD and 1735 controls from a consortium of five North American case-control studies. We collected risk factor information by in-person or telephone interview. Six DRD2 and two DRD3 polymorphisms were genotyped using a common laboratory. Odds ratios were estimated using logistic regression.
Among non-Hispanic whites, homozygous carriers of Taq1A DRD2 (rs1800497) polymorphism had an increased risk of PD compared to homozygous wildtype carriers (OR=1.5, 95% CI 1.0–2.3). In contrast, the direction of association for Taq1A polymorphism was opposite for African Americans, showing an inverse association with PD risk (OR=0.10, 95% CI 0.2–0.7). Among white Hispanics who carried two alleles, the Ser9Gly DRD3 (rs6280) polymorphism was associated with a decreased risk of PD (OR=0.4, 95%CI 0.2–0.8). The inverse association of smoking with PD risk was not modified by any of the DRD2 or DRD3 polymorphisms.
DRD2 polymorphisms are unlikely to be true disease-causing variants; however, three DRD2 polymorphisms (including Taq1A) may be in linkage disequilibrium with possible disease associated variants in the DRD2-ANKK1-NCAM1-TTC12 gene cluster.
Parkinson's disease; dopamine receptor genes; case-control studies; epidemiology
Despite recent advances, multiple myeloma remains incurable and most patients eventually develop progressive disease. Allogeneic hematopoietic stem cell transplantation (allo HCT) offers a potentially curative option in 10–20% of patients with relapsed or refractory disease. We evaluated the outcome of patients undergoing allo HCT with reduced-intensity conditioning (RIC) for relapsed and/or refractory myeloma at our institution.
Fifty-one patients with heavily pretreated, relapsed myeloma, who received RIC allo HCT between 1996 and 2006, were included in this analysis.
Median time from diagnosis to allo HCT was 34 months. Median follow-up in surviving patients was 27 months (3–98). Cumulative transplant-related mortality (TRM) at 1 year was 25%. Progression-free survival (PFS) and overall survival (OS) at 2 years were 19% and 32%, respectively. The incidence of grade II-IV acute or chronic graft-vs-host disease (GVHD) was 27% and 47%, respectively. At the time of this analysis, 12 patients (24%) were alive 7 of whom (14%) were in remission for up to 6 years after allo SCT. A lower β2 microglobulin (<3.3) and a prior autotransplant predicted a lower NRM, longer PFS and OS.
Allo HCT with RIC regimens is associated with acceptable toxicity and durable remission and survival in relapsed or refractory myeloma. Use of RIC allo HCT earlier in the course of the disease may offer greater benefit.
Stem cells still remain one of the most exciting and lucrative options for treatment of variety of nervous system disorders and diseases. Although there are neural stem cells present in adults, the ability of both the peripheral and central nervous system for self-repair is limited at best. As such, there is a great need for a tissue engineering approach to solve nervous system disorders and diseases. In this study, we have developed electrically conductive surfaces with controlled arrays of high aspect ratio nanowires for the growth and maintenance of neural stem cells. The nanowire surfaces were fabricated from polycaprolactone using a novelnanotemplating technique, and were coated with an electrically conductive polymer, polypyrrole. The polypyrrole coated nanowire surfaces were characterized using scanning electron microscopy and X-ray photoelectron spectroscopy. Additionally, the surface resistance of polypyrrole coated nanowire surfaces was measured. C17.2 neural stem cells were used to evaluate the efficacy of the polypyrrole coated nanowire surfaces to promote cell adhesion, proliferation, and differentiation. The results presented here indicate significantly higher cellular adhesion and proliferation on polypyrrole coated nanowire surfaces as compared to control surfaces. The differentiation potential of polypyrrole nanowire surfaces was also evaluated by immunostaining key neuronal markers that are expressed when NSCs differentiate into their respective neural lineages.
Nanowire surfaces; polycaprolactone; polypyrrole; C17.2 neural stem cells; neural tissue engineering
In India, Adenanthera pavonina is traditionally used in the treatment of diabetes mellitus and lipid disorders. In the present study, the antihyperglycaemic and lipid lowering effect of Adenanthera pavonina seed aqueous extract (APSAE) was evaluated using streptozotocin induced diabetes in rats. Streptozotocin was given at the dose of 55 mg/kg, i.p. After induction of diabetes, APSAE was administered for 30 days p. o. and simultaneously different biochemical parameters like plasma glucose, HbA1c, serum triglyceride, cholesterol, LDL-cholesterol and HDL-cholesterol were estimated. Diabetic control showed significant increase (P < 0.01) in plasma glucose, serum triglyceride, cholesterol, LDL-cholesterol and significant decrease (P < 0.01) in serum HDL-cholesterol and HbA1c. Treatment with APSAE showed significant reduction (P < 0.01) in plasma glucose when compared with diabetic control. The elevated levels of serum triglyceride and cholesterol levels were significantly reduced (P < 0.01) by APSAE. APSAE treatment for 30 days showed significant decrease in serum LDL-cholesterol (P < 0.01) and significant increase in serum HDL cholesterol level (P < 0.01). Moreover, diabetic control there was significant decrease in HbA1c which was significantly increased (P < 0.05) by treatment with APSAE. Hence, from the result obtained in the present study it can be confirmed that Adenanthera pavonina has the potential to treat diabetes condition and associated lipid disorders.
Adenanthera pavonina; Streptozotocin; antihyperglycaemic; Lipid lowering; HbA1c
We analysed the results of haematopoietic cell transplantation (HCT) in 30 patients aged 60–78 (median 65) years, with primary myelofibrosis or myelofibrosis evolving from antecedent polycythaemia vera or essential thrombocythaemia. Donors were human leucocyte antigen (HLA)-identical siblings (N = 15) or unrelated individuals (N = 15). Various conditioning regimens were used, ranging from very low intensity (fludarabine plus 2 Gy total body irradiation) to high dose (busulfan plus cyclophosphamide). Stem cell sources were granulocyte colony-stimulating factor mobilized peripheral blood progenitor cells in 29 patients and marrow in one patient. Sustained engraftment was documented in 27 of 30 patients. Day -100 mortality was 13%. With a median follow-up of 22 (range 0.5–69) months, 3-year overall survival and progression-free survival were 45% and 40%, respectively. Currently, 13 patients are surviving. Seven patients died with disease progression at 0.5–22 months, and 10 patients died from other causes at 1.5–37.5 months after HCT. While the selection of older patients for transplantation was probably biased, the present results are encouraging. Motivated older patients with myelofibrosis without substantial comorbid conditions should be offered the option of allogeneic HCT.
myelofibrosis, older patients; haematopoietic cell transplantation
Chemotherapy-induced febrile neutropenia is a medical emergency complicating the treatment of many cancer patients. It is associated with considerable morbidity and mortality, as well as impacting on healthcare resources.
A prospective study of all cases of chemotherapy-induced febrile neutropenia in the South West London Cancer Network was conducted over a 4-month period. Factors including demographics, treatment history, management of febrile neutropenia and outcome were recorded.
Results and conclusi:
Our results reflect those of the recent National Chemotherapy Advisory Group (NCEPOD, 2008)/National Confidential Enquiry into Patient Outcomes and Death reports (NCAG, 2009) and highlight the need for network-wide clinical care pathways to improve outcomes in this area.
neutropenic sepsis; chemotherapy; infection; febrile neutropenia
Microglia, the resident immune cells of the brain, have been implicated in brain injury and various neurological disorders. However, their precise roles in different pathophysiological situations remain enigmatic and may range from detrimental to protective. Targeting the delivery of biologically active compounds to microglia could help elucidate these roles and facilitate the therapeutic modulation of microglial functions in neurological diseases.
Here we employ primary cell cultures and stereotaxic injections into mouse brain to investigate the cell type specific localization of semiconductor quantum dots (QDs) in vitro and in vivo. Two potential receptors for QDs are identified using pharmacological inhibitors and neutralizing antibodies.
In mixed primary cortical cultures, QDs were selectively taken up by microglia; this uptake was decreased by inhibitors of clathrin-dependent endocytosis, implicating the endosomal pathway as the major route of entry for QDs into microglia. Furthermore, inhibiting mannose receptors and macrophage scavenger receptors blocked the uptake of QDs by microglia, indicating that QD uptake occurs through microglia-specific receptor endocytosis. When injected into the brain, QDs were taken up primarily by microglia and with high efficiency. In primary cortical cultures, QDs conjugated to the toxin saporin depleted microglia in mixed primary cortical cultures, protecting neurons in these cultures against amyloid beta-induced neurotoxicity.
These findings demonstrate that QDs can be used to specifically label and modulate microglia in primary cortical cultures and in brain and may allow for the selective delivery of therapeutic agents to these cells.
Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after matched unrelated, related, or mismatched related donor hematopoietic stem-cell transplantation (HSCT). Improved GVHD prevention methods are needed. Pentostatin, an adenosine deaminase inhibitor, leads to lymphocyte depletion with low risk of myelosuppression. We hypothesized that addition of pentostatin to GVHD prophylaxis with tacrolimus and mini-methotrexate may improve outcomes, and we conducted a Bayesian adaptively randomized, controlled, dose-finding study, taking into account toxicity and efficacy.
Patients and Methods
Success was defined as the patient being alive, engrafted, in remission, without GVHD 100 days post-HSCT and no grade ≥ 3 GVHD at any time. Patients were randomly assigned to pentostatin doses of 0, 0.5, 1.0, 1.5, and 2.0 mg/m2 with drug administered on HSCT days 8, 15, 22, and 30. Eligible patients were recipients of mismatched related (n = 10) or unrelated (n = 137) donor HSCT.
Median age was 47 years. Thirty-seven, 10, 29, 61, and 10 patients were assigned to the control and four treatment groups, respectively, with comparable baseline characteristics. Pentostatin doses of 1.0 and 1.5 mg/m2 had the highest success rates (69.0% and 70.5%) versus control (54.1%). The posterior probabilities that the success rates were greater with 1.5 mg/m2 or 1.0 mg/m2 versus control are 0.944 and 0.821, respectively. Hepatic aGVHD rates were 0%, 17.2%, and 11.1%, respectively, for 1.5 mg/m2, 1.0 mg/m2, and control groups. No grades 3 to 4 aGVHD occurred in 11 HLA-mismatched recipients in the 1.5 mg/m2 group.
Pentostatin increased the likelihood of success as defined here, and should be further investigated in larger randomized, confirmatory studies.
Head and neck squamous cell carcinoma (HNSCC) often presents with cervical lymph node metastases and at times the primary tumor cannot be identified despite extensive workup. Lymphoma is the second most common neoplasm in the head and neck region but is seldom synchronous with HNSCC and rarely involves regional mucosal sites. We report herein a rare occurrence of tonsillar involvement by small lymphocytic lymphoma (SLL) incidentally detected during the workup for a cervical lymph node SCC metastasis of a 52-year-old non-smoker male. The microscopic human papillomavirus-positive SCC involving the tonsillar surface and crypts was obscured by SLL leading to the initial designation of ‘unknown primary’. The occult HNSCC are likely explained by small tumor size, quality and quantity of sampling, thoroughness of endoscopic, radiological and pathological assessment or a combination of the above. The coexistence of another tumor such as lymphoma has not yet been reported as a confounding factor in the workup for cervical SCC metastasis. Since oropharyngeal SCC can be very small and Waldeyer’s ring is a common site for lymphoma involvement, identification of such rare collision tumors requires pathologists’ awareness, extensive sampling and occasionally ancillary studies for the accurate diagnosis and staging essential for the correct management.
Head and neck occult carcinoma; Tonsillar carcinoma; Small lymphocytic lymphoma; Collision tumor
Cellular immunoisolation using semi-permeable barriers has been investigated over the past several decades as a promising treatment approach for diseases such as Parkinson’s, Alzheimer’s, and Type 1 diabetes. Typically, polymeric membranes are used for immunoisolation applications; however, recent advances in technology have led to the development of more robust membranes that are able to more completely meet the requirements for a successful immunoisolation device, including well controlled pore size, chemical and mechanical stability, non-biodegradability, and biocompatibility with both the graft tissue as well as the host. It has been shown previously that nanoporous alumina biocapsules can act effectively as immunoisolation devices, and support the viability and functionality of encapsulated β cells. The aim of this investigation was to assess the biocompatibility of the material with host tissue. The cytotoxicity of the capsule, as well as its ability to activate complement and inflammation was studied. Further, the effects of PEG-modification on the tissue response to implanted capsules were studied. Our results have shown that the device is non-toxic and does not induce significant complement activation. Further, in vivo work has demonstrated that implantation of these capsules into the peritoneal cavity of rats induces a transient inflammatory response, and that PEG is useful in minimizing the host response to the material.
bioartificial pancreas; cell encapsulation; alumina; biocompatibility
To assess the familial aggregation of Parkinson’s disease (PD), we compared the cumulative incidence of PD among first-degree relatives of PD cases and controls. We identified newly diagnosed patients with PD (n=573) during 1994–1995 within Kaiser Permanente Medical Care Program (KPMPC) of Northern California and recruited 496 cases (87%) for the case-control study. Of 720 eligible controls matched by birth year and sex to cases, 541 (75%) agreed to participate. Information on family history of PD and other neurodegenerative diseases was obtained by in-person structured interview. We used the reconstructed cohort approach which provides a better estimate of the risk. The cumulative incidence of PD was significantly higher among relatives of PD patients compared to relatives of controls (2.0 versus 0.7%; RR=3.4, 95% CI 1.9–5.9; p=0.0001). The degree of familial aggregation was higher among first degree relatives of Hispanic PD cases compared to Hispanic controls (3.7% versus 0.4%; RR=8.5, 95% CI 1.0–68.9) than it was among non-Hispanic Caucasian cases and controls (2.0% versus 0.8%; RR=2.7, 95% CI 1.5–5.1) (p=0.02). The familial aggregation of PD was stronger among the siblings of PD cases (RR=5.4, 95% CI 1.8–16.0) than among parents (RR=2.7, 95% CI 1.3–5.2). The incidence and familial aggregation of PD is highest among Hispanics, warranting further studies of genetic and environmental risk factors in the Hispanic population.
Parkinson's disease; risk factors; family history; case-control; epidemiology
Despite discrepant results on clinical utility, several trials are already prospectively randomizing non-small cell lung cancer (NSCLC) patients by ERCC1 status. We aimed to characterize the prognostic and predictive effect of ERCC1 by systematic review and meta-analysis.
Eligible studies assessed survival and/or chemotherapy response in NSCLC or SCLC by ERCC1 status. Effect measures of interest were hazard ratio (HR) for survival or relative risk (RR) for chemotherapy response. Random-effects meta-analyses were used to account for between-study heterogeneity, with unadjusted/adjusted effect estimates considered separately.
23 eligible studies provided survival results in 2,726 patients. Substantial heterogeneity was observed in all meta-analyses (I2 always >30%), partly due to variability in thresholds defining ‘low’ and ‘high’ ERCC1. Meta-analysis of unadjusted estimates showed high ERCC1 was associated with significantly worse overall survival in platinum-treated NSCLC (average unadjusted HR = 1.61, 95%CI:1.23–2.1, p = 0.014), but not in NSCLC untreated with chemotherapy (average unadjusted HR = 0.82, 95%CI:0.51–1.31). Meta-analysis of adjusted estimates was limited by variable choice of adjustment factors and potential publication bias (Egger's p<0.0001). There was evidence that high ERCC1 was associated with reduced response to platinum (average RR = 0.80; 95%CI:0.64–0.99). SCLC data were inadequate to draw firm conclusions.
Current evidence suggests high ERCC1 may adversely influence survival and response in platinum-treated NSCLC patients, but not in non-platinum treated, although definitive evidence of a predictive influence is lacking. International consensus is urgently required to provide consistent, validated ERCC1 assessment methodology. ERCC1 assessment for treatment selection should currently be restricted to, and evaluated within, clinical trials.
To assess ovarian follicle function in women with 46,XX spontaneous primary ovarian insufficiency
Case-control with nested prospective cohort
Clinical Research Center, National Institutes of Health
Women with primary ovarian insufficiency without estrogen replacement for two weeks (N=97) and regularly menstruating control women (N=42)
Single injection of 300 IU hrFSH
Main outcome measures
Change in serum estradiol at 24 hours
Antral follicles ≥ 3 mm were detected in 73% (69/95) of patients; both serum estradiol and progesterone levels correlated significantly with maximum follicle diameter in these women. Patients with a maximum follicle diameter ≥ 8 mm had significantly higher serum estradiol and progesterone levels and significantly lower FSH and LH levels as compared to patients without such follicles. In controls estradiol levels increased significantly after FSH administration but in patients this was not the case despite the presence of an antral follicle ≥ 8 mm.
Most women with 46,XX spontaneous primary ovarian insufficiency have antral follicles detectable by ultrasound, suggesting that down-regulation of FSH receptors is not the predominant mechanism of follicle dysfunction. Evidence of progesterone secretion by antral follicles ≥ 8 mm in these patients is consistent with prior histologic evidence that follicle luteinization is the predominant mechanism of follicle dysfunction in this condition. Prospective controlled investigation designed to improve ovulatory function and fertility in these women is indicated.
Primary ovarian insufficiency; hypergonadotropic hypogonadism; premature ovarian failure; premature menopause; lutienized Graafian follicle
To examine factors associated with emotional well-being in women with spontaneous primary ovarian insufficiency
Cross-sectional and case control
Clinical research center, national US health research facility
Women diagnosed with spontaneous 46,XX primary ovarian insufficiency (N=100) at a mean age of 32.4 years and healthy control women of similar age (N=60)
Administration of validated self-reporting instruments
Main Outcome Measure(s)
Illness Uncertainty, Stigma, Goal Disengagement/Reengagement, Purpose in Life, Positive and Negative Affect Schedule, Center of Epidemiologic Studies Depression Scale, State-Trait Anxiety Inventory
Compared to controls, women with spontaneous primary ovarian insufficiency scored adversely on all measures of affect. Illness Uncertainty and Purpose in Life were significant independent factors associated with Anxiety (R2=0.47), Stigma and Purpose in Life were the significant independent factors associated with Depression (R2=0.51), and Goal Reengagement and Purpose in Life were significantly and independently associated with Positive Affect (R2=0.43).
This evidence supports the need for prospective studies. Our findings are consistent with the hypothesis that clinicians could improve the emotional well-being of their patients with primary ovarian insufficiency by a) informing them better about their condition, b) helping them to feel less stigmatized by the disorder, and c) assisting them in developing alternative goals with regard to family planning as well as other goals.
Primary ovarian insufficiency; hypergonadotropic hypogonadism; premature ovarian failure; premature menopause; infertility; illness uncertainty; stigma; goal flexibility
Olfactory Neuroblastoma is a rare malignant tumor of the olfactory tract. Reports in the literature comparing treatment modalities for this tumor are limited.
The SEER database (1973-2006) was queried by diagnosis code to identify patients with Olfactory Neuroblastoma. Kaplan-Meier was used to estimate survival distributions based on treatment modality. Differences in survival distributions were determined by the log-rank test. A Cox multiple regression analysis was then performed using treatment, race, SEER historic stage, sex, age at diagnosis, year at diagnosis and SEER geographic registry.
A total of 511 Olfactory Neuroblastoma cases were reported. Five year overall survival, stratified by treatment modality was: 73% for surgery with radiotherapy, 68% for surgery only, 35% for radiotherapy only, and 26% for neither surgery nor radiotherapy. There was a significant difference in overall survival between the four treatment groups (p < 0.01). At ten years, overall survival stratified by treatment modality and stage, there was no significant improvement in survival with the addition of radiation to surgery.
Best survival results were obtained for surgery with radiotherapy.
Small cell lung cancer (SCLC) is a significant health problem worldwide because of its high propensity for relapse. This review discusses existing and future therapies for the treatment of SCLC.
small cell lung cancer; chemotherapy; relapsed SCLC; treatment
Neonatal exposure to an immunological challenge (lipopolysaccharide, LPS) increases the activity of hypothalamo-pituitary–adrenal axis and sensitises the GNRH pulse generator to the inhibitory influence of stress in adult rats. We investigated the effects of neonatal exposure to LPS on various reproductive parameters during puberty and into adulthood in female rats. LPS (50 μg/kg, i.p.) or saline was administered on postnatal days 3 and 5. Vaginal opening was recorded, and oestrous cyclicity was monitored immediately post puberty and again at 8–9 weeks of age. At 10 weeks of age, the ovaries were removed and the number of follicles was counted, together with the thickness of the theca interna of the largest antral follicles. Ovarian sympathetic nerve activity was assessed immunohistochemically by measurement of the levels of ovarian low-affinity receptor of nerve growth factor (p75NGFR). In rats exposed to LPS in early life, there was a significant delay in puberty and disruption of oestrous cyclicity immediately post puberty, which persisted into adulthood. The follicle reserve was decreased, the thickness of the theca interna increased and the expression profile of ovarian p75NGFR increased in the neonatal LPS-treated animals. These data suggest that exposure to LPS during early neonatal life can have long-term dysfunctional effects on the female reproductive system, which might involve, at least in part, increased ovarian sympathetic nerve activity.
N-acylhomoserine lactone (AHL)-based quorum sensing (QS) systems have been described in many plant-associated Gram-negative bacteria to control certain beneficial phenotypic traits, such as production of biocontrol factors and plant growth promotion. However, the role of AHL-mediated signalling in the endophytic strains of plant-associated Serratia is still poorly understood. An endophytic Serratia sp. G3 with biocontrol potential and high levels of AHL signal production was isolated from the stems of wheat and the role of QS in this isolate was determined.
Strain G3 classified as Serratia plymuthica based on 16S rRNA was subjected to phylogenetic analysis. Using primers to conserved sequences of luxIR homologues from the Serratia genus, splIR and spsIR from the chromosome of strain G3 were cloned and sequenced. AHL profiles from strain G3 and Escherichia coli DH5α expressing splI or spsI from recombinant plasmids were identified by liquid chromatography-tandem mass spectrometry. This revealed that the most abundant AHL signals produced by SplI in E. coli were N-3-oxo-hexanoylhomoserine lactone (3-oxo-C6-HSL), N-3-oxo-heptanoylhomoserine lactone (3-oxo-C7-HSL), N-3-hydroxy-hexanoylhomoserine lactone (3-hydroxy-C6-HSL), N-hexanoylhomoserine lactone (C6-HSL), and N-heptanoyl homoserine lactone (C7-HSL); whereas SpsI was primarily responsible for the synthesis of N-butyrylhomoserine lactone (C4-HSL) and N-pentanoylhomoserine lactone (C5-HSL). Furthermore, a quorum quenching analysis by heterologous expression of the Bacillus A24 AiiA lactonase in strain G3 enabled the identification of the AHL-regulated biocontrol-related traits. Depletion of AHLs with this lactonase resulted in altered adhesion and biofilm formation using a microtiter plate assay and flow cells coupled with confocal laser scanning microscopy respectively. This was different from the closely related S. plymuthica strains HRO-C48 and RVH1, where biofilm formation for both strains is AHL-independent. In addition, QS in G3 positively regulated antifungal activity, production of exoenzymes, but negatively regulated production of indol-3-acetic acid (IAA), which is in agreement with previous reports in strain HRO-C48. However, in contrast to HRO-C48, swimming motility was not controlled by AHL-mediated QS.
This is the first report of the characterisation of two AHL-based quorum sensing systems in the same isolate of the genus Serratia. Our results show that the QS network is involved in the global regulation of biocontrol-related traits in the endophytic strain G3. However, although free-living and endophytic S. plymuthica share some conservation on QS phenotypic regulation, the control of motility and biofilm formation seems to be strain-specific and possible linked to the life-style of this organism.
The aqueous leaves extract of Sesbania sesban (L) Merr. (Family: Fabaceae) was evaluated for its antidiabetic potential on normal and streptozotocin (STZ)-induced diabetic rats. In the chronic model, the aqueous extract was administered to normal and STZ- induced diabetic rats at the doses of 250 and 500 mg/kg body weight (b.w.) p.o. per day for 30 days. The fasting Blood Glucose Levels (BGL), serum insulin level and biochemical data such as glycosylated hemoglobin, Total Cholesterol (TC), Triglycerides (TG), High Density Lipoproteins (HDL) and Low Density Lipoproteins (LDL) were evaluated and all were compared to that of the known anti-diabetic drug glibenclamide (0.25 mg/kg b.w.). The statistical data indicated significant increase in the body weight, liver glycogen, serum insulin and HDL levels and decrease in blood glucose, glycosylated hemoglobin, total cholesterol and serum triglycerides when compared with glibenclamide. Thus the aqueous leaves extract of Sesbania sesban had beneficial effects in reducing the elevated blood glucose level and lipid profile of STZ-induced diabetic rats.
Diabetes mellitus; Hyperglycemia; Sesbania sesban; Streptozotocin
The overall purpose of this study was to establish human head and neck squamous cell carcinoma (HNSCC) xenografts in mice by transplantation of surgical tumor tissue and to characterize the growth, histologic and vascular properties of these xenografts. Primary surgical specimens of HNSCC were xenografted into eight-to-twelve week old severe combined immunodeficiency (SCID) mice. Histologic features of primary HNSCC specimens, initial and established xenografts were compared for tumors established from three different head and neck subsites, namely, oral cavity, larynx and base of tongue (one tumor per site). Growth rates of xenografts were compared along with magnetic resonance imaging (MRI) measures of tumor vascularity and correlative CD31-immunostaining. Initial and established xenografts from all three sites demonstrated a squamous phenotype similar to the original patient tumor histology. Established xenografts of oral cavity and larynx exhibited increased keratinization (H&E) compared to initial xenografts and the primary tumor. No differences in tumor growth rates were observed between established xenografts from the different subsites. Xenografts established from SCC of the larynx exhibited increased microvessel density and lumen area (CD31 staining) along with enhanced permeability to the MR contrast agent compared to oral cavity and base of tongue tumors. Our results show that the combination of non-invasive imaging along with histologic evaluation of patient tumor xenografts offers a valuable platform for preclinical investigations in head and neck cancer. However, it is important to recognize the influence of tumor-host interactions on the histologic phenotype of transplanted tumors.
Head and neck cancers; squamous cell carcinoma; patient tumor xenografts; magnetic resonance imaging; histopathology