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Cancer-associated fibroblasts (CAFs) are a key component of tumors. We aimed to profile the proteome of cancer cell lines representing three common cancer types (lung, colorectal and pancreatic) and a representative CAF cell line from each tumor type to gain insight into CAF function and novel CAF biomarkers. We used isobaric labeling, liquid chromatography and mass spectrometry to evaluate the proteome of 9 cancer and 3 CAF cell lines. Of the 9460 proteins evaluated, functional enrichment analysis revealed an upregulation of N-glycan biosynthesis and extracellular matrix proteins in CAFs. 85 proteins had 16-fold higher expression in CAFs compared to cancer cells, including previously known CAF markers like fibroblast activation protein (FAP). Novel overexpressed CAF biomarkers included heat shock protein β-6 (HSPB6/HSP20) and cyclooxygenase 1 (PTGS1/COX1). SiRNA knockdown of the genes encoding these proteins did not reduce contractility in lung CAFs, suggesting they were not crucial to this function. Immunohistochemical analysis of 30 tumor samples (10 lung, 10 colorectal and 10 pancreatic) showed restricted HSPB6 and PTGS1 expression in the stroma. Therefore, we describe an unbiased differential proteome analysis of CAFs compared to cancer cells, which revealed higher expression of HSPB6 and PTGS1 in CAFs. Data are available via ProteomeXchange (PXD040360). SIGNIFICANCE: Cancer-associated fibroblasts (CAFs) are highly abundant stromal cells present in tumors. CAFs are known to influence tumor progression and drug resistance. Characterizing the proteome of CAFs could give potential insights into new stromal drug targets and biomarkers. Mass spectrometry-based analysis comparing proteomic profiles of CAFs and cancers characterized 9460 proteins of which 85 proteins had 16-fold higher expression in CAFs compared to cancer cells. Further interrogation of this rich resource could provide insight into the function of CAFs and could reveal putative stromal targets. We describe for the first time that heat shock protein β-6 (HSPB6/HSP20) and cyclooxygenase 1 (PTGS1/COX1) are overexpressed in CAFs compared to cancer cells., Competing Interests: Declaration of Competing Interest All authors are an employee of The Institute of Cancer Research, which has commercial interest in abiraterone and PARP inhibition in DNA repair defective cancers and the development of HSP90, PI3K, HDAC, AKT, ROCK, RAF, CHK1, MPS-1 and HSF-1 inhibitors. (no personal income). J.B has served on advisory boards and received fees from companies including Amgen, AstraZeneca, Astellas, Bayer, Bioxcel Therapeutics, Daiichi, Genentech/Roche, GSK, Harpoon, ImCheck Therapeutics, Janssen, Merck Serono, Merck Sharp & Dohme, Pfizer, Sanofi Aventis. J.B has also received funding or other support from AstraZeneca, Astellas, Bayer, Cellcentric, Daiichi, Genentech, Genmab, GSK, Janssen, Merck Serono, MSD, Menarini/Silicon Biosystems, Orion, Sanofi Aventis, Sierra Oncology, Taiho, Pfizer, Vertex. J.B was named as an inventor, with no financial interest for patent 8,822,438, submitted by Janssen that covers the use of abiraterone acetate with corticosteroids. J.B has been the CI/PI of many industry sponsored clinical trials. U.B has served on advisory boards and received fees from companies including Carrick Therapeutics and Pegasy. U.B has received grants from Avacta, BTG international, Verastem, Carrick Therapeutics and Chugai., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Overactivation of Pyrin is the cause of the inflammatory diseases Mediterranean Fever and Pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND). Binding of 14-3-3 proteins reduces the pro-inflammatory activity of Pyrin, hence small molecules that stabilize the Pyrin/14-3-3 complex could convey an anti-inflammatory effect. We have solved the atomic resolution crystal structures of phosphorylated peptides derived from PyrinpS208 and PyrinpS242 - the two principle 14-3-3 binding sites in Pyrin - in complex with 14-3-3 and analyzed the ligandability of these protein-peptide interfaces by crystal-based fragment soaking. The complex between 14-3-3 and PyrinpS242 appears to be much more amenable for small-molecule binding than that of 14-3-3/PyrinpS208. Consequently, only for the 14-3-3/PyrinpS242 complex could we find an interface-binding fragment, validating protein crystallography and fragment soaking as a method to evaluate the ligandability of protein surfaces., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Despite growing interest in family planning alongside surgical training, significant barriers exist including time constraints, stigma, and lack of paid leave and formal policies. We currently lack a deep understanding of the challenges residents face and how practice cultures may prohibit successful policy enactment., Objective: To investigate residents' perspectives surrounding parenting and childbearing during neurosurgical residency in the United States and Canada., Methods: A cross-sectional, qualitative study methodology was used, including focus groups with neurosurgical residents. Purposive sampling was employed to capture a broad range of perspectives including stage of training, geographical location, and gender. Data collection and analysis occurred in parallel, using a thematic analysis approach. Data collection continued until no new themes relating to the research questions were identified., Results: Notable challenges included lack of formal family leave policies, time constraints, insufficient clinical human resources, physical health concerns, lack of lactation accommodations, and lack of mentorship. A subset of barriers were uncovered that stem specifically from workplace cultures, including gender norms, difficulty in asking for help, concerns for inconveniencing others, and pressures to time parental leave during research blocks. Several positive changes were identified including growing awareness and female representation, and benefits of the dual surgeon-parent identity., Conclusion: While parenting during neurosurgery residency is becoming increasingly common, significant practical and cultural barriers persist including a marked absence of formal policies. Culture shifts are essential in ensuring opportunities for life outside of medicine for all residents, irrespective of family status., (Copyright © 2023 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: RNA sequencing (RNAseq) analysis is emerging as a clinical research or diagnostic approach for cytologic samples, but there is need for formal comparison of different sample preparation methods in the cytology laboratory to identify which pre-analytic methods could provide alternatives to formalin-fixed paraffin-embedded (FFPE) sections., Materials and Methods: We prepared 13 malignant effusions (metastatic estrogen receptor-positive breast cancer) in the cytology laboratory using 6 routine cytologic methods: FFPE cell block, Carnoy's solution, 95% ethanol (EtOH), air-dried and Diff-Quik, ThinPrep, and SurePath preparations. Measurements of RNA quality, expression of 2 multigene expression signatures, molecular subtype, and 4 common activating mutation sites in each preparation were compared with fresh frozen (FF) cell pellet in RNA preservative using distribution of fragment length and concordance correlation coefficient (CCC)., Results: The fraction of RNA fragments measuring 200 bases or more (DV200) were 24% higher from cytospins fixed in Carnoy's solution or 95% EtOH than DV200 from FFPE cell blocks. SurePath samples failed RNAseq quality control. There was high concordance of gene expression measurements with FF samples using cytospins fixed in Carnoy's solution, 95% EtOH, Diff-Quik (CCC = 0.829, 0.812, 0.760, respectively), or ThinPrep (CCC = 0.736), but lower using FFPE cell block (CCC = 0.564). The proportion of mutant transcripts was concordant between FF and any cytologic preparation methods., Conclusions: Cytospin preparations fixed with Carnoy's or 95% ETOH then Papanicolaou stained produced RNAseq results that were equivalent to FF samples and superior to FFPE cell block sections., (Copyright © 2022. Published by Elsevier Inc.)

Objective: Gross total resection (GTR) is not always possible in acromegalic patients, especially in patients with invasive growth hormone-secreting adenomas. We analyzed the biochemical remission outcome in relation to extent of tumor resection and effectiveness of medical treatment in cases of remnant tumor., Methods: Retrospective analysis was performed of acromegalic patients operated on between 2002 and 2017. Preoperative imaging, tumor invasiveness, extent of resection, and biochemical remission were collected. Patients with tumor remnant not amenable to second surgery began medical treatment. The relationship between pituitary adenoma remnant volume and final biochemical outcome was analyzed., Results: Of 120 acromegalic patients operated on, 82 underwent transsphenoidal microsurgery and 38 underwent endonasal endoscopic approach. GTR was achieved in 72 cases (60%); subtotal resection (STR), 21 (17.5%) cases; and partial resection, 27 (22.5%) cases. There was a nonsignificant higher rate of GTR/STR in patients who underwent endonasal endoscopic approach. However, a significantly higher remission rate (89.45% vs. 67.1%) was achieved in these patients (P < 0.01). Greater tumor volume and invasiveness were associated with a lower remission (P < 0.05). Patients with tumor remnant who achieved biochemical remission with added medical therapy had a significantly smaller tumor volume (P < 0.001)., Conclusions: The more aggressive surgical resection is, the greater the chance of attaining final biochemical remission, whether or not GTR is achieved. Medical therapy effectiveness is enhanced in cases with STR. Invasive growth hormone-secreting macroadenomas that are not surgically amenable to total resection are best managed with a combination of safe STR and medical treatment., (Copyright © 2021. Published by Elsevier Inc.)

The rapid rise in obesity prevalence is life-style related and tackling this problem requires a pro-active multi-faceted approach to management. A private health care provider in Melbourne, Australia, developed a multidisciplinary rehabilitation program for patients who had undergone bariatric surgery or receiving pharmacological weight loss treatments. The study aim was to assess the programs' effect on patients' quality of life, mental well-being, and eating behaviours., Methods: A prospective, observational, before and after study design was used. A total of 54 patients, 27 who had bariatric surgery and 27 receiving pharmacotherapy participated. Outcome measures were: change in weight and BMI, intuitive eating scale, impact of weight on quality of life scale and the depression, anxiety and stress scale., Results: Both medical and surgical patients reported improvements in their health-related quality of life and eating behaviours. Despite this, at program completion 71.4% of patients who had bariatric surgery reported severe anxiety and 52.4% severe stress levels., Conclusion: Participation in a rehabilitation program that provided patients with peer support and access to expert advice supported patients to make healthy eating choices and improved their quality of life. The high prevalence of stress and anxiety related symptoms highlights the need to provide individuals who have undergone bariatric surgery with ongoing mental health support., (Copyright © 2021 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the cascade of HIV care in Oman in 2018 and the longitudinal change in each step from 2015 to 2018., Methods: Population-based data on all diagnosed people living with HIV reported to the National AIDS Programme in 1984-2018 were used., Results: As of December 31, 2018, the estimated number of people living with HIV in Oman was 3030; 1532 (50.6%) were aware of their infection. Of the diagnosed patients, 95.9% were linked to care, 85.8% were retained in care, and 84.3% were on ART. The proportions of patients with viral suppression out of all people with HIV, the diagnosed persons, and those on ART were 37.3%, 73.7%, and 87.5%, respectively. The proportion of patients linked to care increased from 72.6% in 2015 to 95.6% in 2018 (p < 0.001). Only 57% (947/1661) were retained in care in 2015, which increased to 76.9% (1193/1552) in 2017 and 85.8% (1314/1532) in 2018 (p < 0.001). Viral suppression increased from 75.7% (672/888) in 2015 to 84.5% (859/1017) in 2016 and 87.5% (1129/1291) in 2018 (p < 0.001)., Conclusions: A sustained improvement in linkage to care, retention in care, ART coverage, and viral suppression was observed amongst people living with HIV in Oman in 2015-2018., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: The cancer care coordinator (CCC) role has become a priority in providing coordinated, patient-centered, supported care for patients, and their families experiencing cancer. The CCC role exists with heterogeneity across tumor streams, clinical disciplines, and institutions. This study explored CCCs perceptions and experiences of their role, scope of practice, and potential for future role development., Methods: This research used a mixed methods design. Focus groups and individual interviews were conducted with a purposive sample of 16 CCCs from two tertiary public teaching hospitals in Melbourne, Australia. A thematic analysis approach was used. A quantitative record of relative time spent on tasks was also collected., Results: Three major themes were identified: (1) Perceptions of role legitimacy, (2) Structure and funding of the role determines scope of practice, and (3) Reflections on the potential for the role. Variability was evident in predominant tasks undertaken, integration into the unit, level of patient contact, and regard from other professional colleagues. Variability appears to relate to employment time assigned to the role, and history and structure of the role., Conclusions: The findings underline the need when establishing and reviewing CCC roles for explicit attention to be given to the reporting, integration, structural, and collegiate support for the role as this will profoundly influence its success., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Ann & Joshua Medical Publishing Co. Ltd.)

Objective: The atrium is the most common location for masses in the lateral ventricle. However, access to this area is limited owing to its deep location and adjacent eloquent neurovascular structures, such as the choroidal arteries, perisylvian white matter (WM) tracts, and optic radiations. We investigated the feasibility and safety of an endoscopic approach to the atrium via the anterior middle temporal gyrus (MTG)., Methods: Radiological assessment of a minimally invasive surgical trajectory to the atrium was achieved in 10 patients. Surgical simulation to assess the feasibility of our endoscopic approach was performed on 24 cadaveric specimens using a transzygomatic corridor and temporal craniotomy. Preoperative computed tomography was performed to confirm the surgical trajectory using neuronavigation. Using Klinger's method, 5 hemispheres were dissected to assess the relationship of our approach to the WM tracts., Results: The optimal entry angle to reach the atrium through the anterior MTG was related to the temporal horn in the axial plane and to the Sylvian fissure in the sagittal plane. Our entry point in the anterior MTG was 19 ± 1.92 mm from the temporal pole. The transparenchymal distance to atrium was 24.55 ± 4.3 mm. The WM dissections confirmed that our approach did not violate the optic radiations, uncinate fasciculus, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, or superior longitudinal fasciculus., Conclusion: Our findings have confirmed the feasibility of an anterior endoscopic approach to the atrium through the anterior MTG, with preservation of the functional integrity of the eloquent cortex and WM tracts., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Preoperative radiologic evaluation of pituitary adenomas is essential. Despite the efforts made to determine the achieved resection grade after pituitary adenoma surgery, there is a high level of disagreement among all the available classifications and measurement methods used. Our study aimed to determine pituitary adenoma imaging features, easily obtained from preoperative magnetic resonance, which could be used as resection predictor variables. Second, we analyzed the usefulness of the ellipsoid method in pituitary adenoma volume determination., Methods: Two-hundred and ninety-four pituitary adenomas, which were surgically treated in our department, were retrospectively analyzed. Age, gender, surgical approach, hormonal status, greater tumor diameter, volume, cavernous sinus invasion, and extent of resection were evaluated., Results: One-hundred and forty-eight surgical procedures were conducted with a microsurgical transsphenoidal approach whereas 146 were conducted with an endoscopic endonasal approach. Gross total resection was achieved in 54.08% of cases. There were no significant differences in the extent of resection regarding the approach used, age, gender, or hormonal production by the tumor. Only Knosp grade (P < 0.001) and tumor volume (P < 0.05) had a statistically and independent significant relationship with the extent of resection. Furthermore, we found a high correlation between the calculated volume, using the ellipsoid method, and the volume measurement obtained with complex planimetry methods., Conclusions: Pituitary adenoma volume and cavernous sinus invasion, graded with the Knosp scale, are 2 pituitary tumor features that, when used in combination, predict the complexity of the surgery and the difficulty of achieving gross total resection in pituitary adenoma surgery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Immobilization of weight bearing skeletons or microgravity results in disuse osteoporosis in both human and animals. Our previous study demonstrated that electrical stimulation at the dorsal root ganglion (DRG) with an implantable micro-electrical stimulation system (IMESS) could trigger secretion of bone anabolic calcitonin gene-related peptide (CGRP) and prevent bone loss in a short-term hindlimb unloading rat model. This study was designed to further investigate whether electrical stimulation to the DRG could prevent bone loss due to prolonged unloading., Methods: Eighteen adult rats were randomly assigned into three groups: cage control (CC), hindlimb unloading (HU), and hindlimb unloading with electrical stimulation (HUES). Electrical stimulation was applied via IMESS to the right DRGs at vertebral levels L4-L6 in HUES group for 6 weeks., Results: Following unloading for 6 weeks, proximal tibia metaphysis was shown 64.0% decrease in bone mineral content (BMC) and 47.0% decrease in bone mineral density (BMD) in HU group while significant reduced bone lose with 2.7% increase in total BMC and only 9.2% decrease in total BMD in HUES group. Diaphyseal BMD decreased significantly in both HU and HUES group as compared with CC group. There was enhancement of CGRP expression in the DRGs in HUES group., Conclusion: This experimental study proved the proposed concept using electrical stimulation at the DRG for prevention of disuse-induced bone loss in a rat hindlimb suspension model., (© 2016 International Neuromodulation Society.)

Background: Vertical sleeve gastrectomy (VSG) ameliorates metabolic complications in obese and diabetic patients through unknown mechanisms., Objective: The objective of this study was to investigate the role of lipocalin-type prostaglandin D 2 synthase (L-PGDS) in glucose regulation in response to VSG using L-PGDS knock-out (KO), knock-in (KI), and C57BL/6 (wild type) mice., Setting: Winthrop University Hospital Research Institute., Methods: Animals were divided into 6 groups: L-PGDS KO sham/VSG (n = 5), L-PGDS KI sham/VSG (n = 5), and C57BL/6 (wild type) sham/VSG (n = 5). Related parameters were measured in fasting animals after 10 weeks., Results: Our intraperitoneal glucose tolerance tests and homeostatic model assessment insulin resistance results showed significant glycemic improvement 10 weeks post-VSG in both C57BL/6 and KI groups compared with the sham group. In contrast, the KO group developed glucose intolerance and insulin resistance similar to or greater than the sham group 10 weeks post-VSG. Interestingly, weight gain was insignificant 10 weeks post-VSG in all the groups and even trended higher in the KO group compared with sham. Peptide YY levels in the KO group post-VSG were slightly increased but significantly less than other groups. Similarly, the KO group showed significantly less leptin sensitivity in response to VSG compared with the KI group. Total cholesterol level remained unchanged in all groups irrespective of sham or surgery but interestingly, the KO group had significantly higher cholesterol levels. In parallel, adipocyte size was also found to be significantly increased in the KO group post-VSG compared with the sham group., Conclusion: Our findings propose that L-PGDS plays an important role in the beneficial metabolic effects observed after VSG., (Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Perinatal stress is associated with adverse maternal and infant outcomes. Mindfulness training may offer a safe and acceptable strategy to support perinatal mental health., Aim: To critically appraise and synthesise the best available evidence regarding the effectiveness of mindfulness training during pregnancy to support perinatal mental health., Methods: The search for relevant studies was conducted in six electronic databases and in the grey literature. Eligible studies were assessed for methodological quality according to standardised critical appraisal instruments. Data were extracted and recorded on a pre-designed form and then entered into Review Manager., Findings: Nine studies were included in the data synthesis. It was not appropriate to combine the study results because of the variation in methodologies and the interventions tested. Statistically significant improvements were found in small studies of women undertaking mindfulness awareness training in one study for stress (mean difference (MD) -5.28, 95% confidence intervals (CI) -10.4 to -0.42, n=22), two for depression (for example MD -5.48, 95% CI -8.96 to -2.0, n=46) and four for anxiety (for example, MD -6.50, 95% CI -10.95 to -2.05, n=32). However the findings of this review are limited by significant methodological issues within the current research studies., Conclusion: There is insufficient evidence from high quality research on which to base recommendations about the effectiveness of mindfulness to promote perinatal mental health. The limited positive findings support the design and conduct of adequately powered, longitudinal randomised controlled trials, with active controls., (Copyright © 2015 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Background: Dietary magnesium might be related to colorectal tumor risk through the pivotal roles of magnesium in cellular metabolism, insulin resistance, and systemic inflammation., Objective: We evaluated the hypothesis of whether higher dietary magnesium intake is associated with reduced colorectal tumor risk., Design: A case-control study on colorectal adenomas (768 cases; 709 polyp-free control subjects) and a meta-analysis of colorectal adenomas (3 case-control studies) and carcinomas (6 prospective cohort studies) were conducted. Dietary magnesium was estimated from food-frequency questionnaires in the case-control study and most studies in the meta-analyses. Data analysis comprised multiple logistic regression analysis (case-control study) and fixed- and random-effects meta-analyses., Results: The case-control study showed a nonsignificant inverse association between dietary magnesium intake and risk of colorectal adenomas (OR for every 100-mg/d increase: 0.81; 95% CI: 0.62, 1.06). However, inverse associations were observed only in subjects with BMI (in kg/m²) ≥25, in subjects aged ≥55 y, and for advanced adenomas. Associations did not vary by the calcium-to-magnesium intake ratio. In the meta-analysis, every 100-mg/d increase in magnesium intake was associated with 13% lower risk of colorectal adenomas (OR: 0.87; 95% CI: 0.75, 1.00) and 12% lower risk of colorectal cancer (RR: 0.88; 95% CI: 0.81, 0.97)., Conclusions: Our findings support the hypothesis that higher intakes of dietary magnesium are associated with lower risk of colorectal tumors. The consumption of magnesium-rich foods may be a new avenue to explore further in the search for cancer-prevention strategies.

Background: Prostate cancer is a growing public health problem. Several human studies have shown a potentially protective effect of selenium, but the conclusions from published reports are inconsistent., Objective: The objective was to examine the evidence for relations between selenium intake, selenium status, and prostate cancer risk., Design: This was a systematic review and meta-analysis of randomized controlled trials, case-control studies, and prospective cohort studies. The World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project database was searched up to September 2010. The studies included reported measurements of selenium intake or status (plasma, serum, or toenail selenium), assessments of prostate cancer cases (number of events), and the RR in the adult population. Meta-analyses were performed, and study quality, heterogeneity, and small study effects were assessed. Dose-response meta-analyses were used, with restricted cubic splines and fractional polynomials for nonlinear trends, to investigate the association between selenium status and prostate cancer risk., Results: Twelve studies with a total of 13,254 participants and 5007 cases of prostate cancer were included. The relation between plasma/serum selenium and prostate cancer in a nonlinear dose-response meta-analysis showed that the risk decreased with increasing plasma/serum selenium up to 170 ng/mL. Three high-quality studies included in the meta-analysis of toenail selenium and cancer risk indicated a reduction in prostate cancer risk (estimated RR: 0.29; 95% CI: 0.14, 0.61) with a toenail selenium concentration between 0.85 and 0.94 μg/g., Conclusion: The relation between selenium status and decreased prostate cancer risk was examined over a relatively narrow range of selenium status; further studies in low-selenium populations are required.

Background: Previous studies of the association between intake of dairy products and colorectal cancer risk have indicated an inverse association with milk, however, the evidence for cheese or other dairy products is inconsistent., Methods: We conducted a systematic review and meta-analysis to clarify the shape of the dose-response relationship between dairy products and colorectal cancer risk. We searched the PubMed database for prospective studies published up to May 2010. Summary relative risks (RRs) were estimated using a random effects model., Results: Nineteen cohort studies were included. The summary RR was 0.83 (95% CI [confidence interval]: 0.78-0.88, I2=25%) per 400 g/day of total dairy products, 0.91 (95% CI: 0.85-0.94, I2=0%) per 200 g/day of milk intake and 0.96 (95% CI: 0.83-1.12, I2=28%) per 50 g/day of cheese. Inverse associations were observed in both men and women but were restricted to colon cancer. There was evidence of a nonlinear association between milk and total dairy products and colorectal cancer risk, P<0.001, and the inverse associations appeared to be the strongest at the higher range of intake., Conclusion: This meta-analysis shows that milk and total dairy products, but not cheese or other dairy products, are associated with a reduction in colorectal cancer risk.

The feasibility of using pollen-shape carriers in dry powder inhalation is studied. Pollen-shape hydroxyapatite (HA) particles are synthesized with a geometric diameter range from 21.1 to 48.6 microm and effective density range from 0.21 to 0.41 g/cm(3). The flowability of the particles is characterized by the Carr's compressibility index (CI) and angle of slide (theta). The HA carriers are found to have better flowability than commonly used lactose (LA) carrier with similar size range. The HA carriers are also found to be capable of high drug attachment. The aerosolization and deposition properties of a model drug are compared using HA and LA as carriers. Results indicate that pollen-shape HA carriers have good potential to be used as drug carrier in dry powder inhalation. It can give higher drug emission and respirable fraction than traditional LA carriers., (2009 Wiley-Liss, Inc. and the American Pharmacists Association)

The marine ecosystem of the Pearl River Delta, located on the southern coast of China, has been heavily exploited following the rapid economic growth that has occurred since the 1980s. This investigation aimed to elucidate trace organic contamination in marine biota inhabiting the Pearl River Delta area. Biota samples, including green-lipped mussels (Perna viridis), oysters (Crassostrea rivularis) and shrimp (Penaeus orientalis) were sampled from 16 stations fringing the Estuary. Elevated concentrations (on a dry weight basis) of polycyclic aromatic hydrocarbons (27.8-1041.0 ng/g), petroleum hydrocarbons (1.7-2345.4 microg/g), polychlorinated biphenyls (2.1-108.8 ng/g), DDTs (1.9-79.0 ng/g), and hexachlorocyclohexanes (n.d.-38.4 ng/g) were recorded. A human health risk assessment was conducted to estimate the risk to local residents associated with the consumption of biota collected from the Pearl River Estuary. The results indicated that PCBs were at levels that may cause deleterious health effects in populations that consume large amounts of seafood. However, it would be instructive to establish health criteria for trace organic contaminants that are specific to the local populations, in order to derive a more accurate and relevant health risk assessment.

Conventional methods for generating monocyte-derived dendritic cells (DC) for clinical trials utilize the property of plastic adherence to select monocytes from leukapheresis samples. This method is labor-intensive and has the potential for contamination at various steps. We evaluated a large-scale monocyte enrichment procedure using a cell selector (Isolex 300i(R)) followed by culture in a sterile bag system (Stericell(R)) for generation of DC. DC generated in tissue culture flasks after monocyte selection by plastic adherence were compared to those generated in Stericell(R) bags after monocyte enrichment by negative selection with the Isolex(R) 300i. DC were matured with lipopolysaccharide and pulsed with a peptide derived from the melanoma antigen gp100. Peptide-pulsed DC cultured by the two techniques were evaluated for phenotype, viability, ability to induce allogeneic and peptide-specific autologous proliferative responses as well as peptide-specific cytotoxic T-cell responses. The mean monocyte yield from leukapheresis collections was 17+/-2.4%, which increased to 52+/-11% after Isolex(R) selection. The DC yield of plated mononuclear cells from flasks or bags was 2.7+/-0.96% and 4.84+/-2.65%, respectively. DC cultured by both methods expressed high levels of CD86, CD80, CD40, CD83, CD44, CD11c and CD58, and was comparable in their ability to induce allogeneic and peptide-specific autologous proliferative responses as well as gp100 peptide-specific cytotoxic T-cell responses. These results indicate that potent monocyte-derived DC can be generated in a closed culture bag system after monocyte enrichment by immunomagnetic negative selection. Due to the closed nature of the enrichment and culture systems, the potential for contamination is minimized. This protocol is well suited for culturing large numbers of DC for clinical immunotherapy trials.

The cutting efficiency and the effects of instrumentation on curved canal shape of both stainless-steel and nickel-titanium nonstandardized ProFile Series 29 hand instruments and stainless-steel Flexoreamer were investigated under standardized conditions. Concerning cutting efficiency in rotary motion, the Flexoreamer had significantly (p < 0.01) greater cutting efficiency than stainless-steel ProFiles and nickel-titanium ProFiles. Changes in the canal shape differed significantly between the different instruments at all measuring points (p < 0.001). After instrumentation with Flexoreamers with inclusion of two half-sizes (#17 and #22), there were fewer undesirable changes in canal shape compared with both stainless-steel and nickel-titanium ProFile Series 29 instruments. In this study, it seemed that flexible stainless-steel instruments with noncutting tips were superior to the nonstandardized ProFile Series 29 instruments with regard to cutting efficiency and instrumentation of curved canals.

Dendritic cells (DC) are professional antigen-presenting cells which stimulate strong proliferative and cytolytic T cell responses. Stimulation of CD40 on dendritic cells by its ligands and anti-CD40 antibodies induces maturation and enhances DC stimulatory ability. In order to understand the mechanism by which ligand:CD40 interactions augment DC function, we assessed the role of T cell stimulatory cytokines IL-12 and IL-15 in the function of DC stimulated with soluble trimeric CD40L, a recombinant fusion protein incorporating three covalently linked extracellular CD40L domains (huCD40LT). Peripheral blood derived DC treated with huCD40LT and/or IFN-gamma were used to stimulate T cell responses in vitro to specific antigens. DC treated with huCD40LT or IFN-gamma/huCD40LT stimulated enhanced T cell proliferation to CASTA, a soluble protein from C. albicans, induced T cells with augmented antigen-specific lysis, and increased the yield of antigen-specific IFN-gamma-producing T cells. IL-15 production by DC was enhanced in cultures treated with huCD40LT and correlated with expansion of antigen-specific cytolytic T cells. Addition of a neutralizing anti-IL-15 monoclonal antibody inhibited the expansion of viral and tumor antigen-specific T cells stimulated by IFN-gamma and huCD40LT-treated DC. In contrast, this enhanced stimulatory ability of DC did not appear to depend on synthesis of IL-12 since huCD40LT treatment stimulated the generation of antigen-specific cytokine producing and cytolytic T cells without increased IL-12 production. Addition of anti-IL-12 monoclonal antibody did not inhibit expansion of these cells. These data suggest that production of IL-15 but not IL-12 is an important factor in the enhanced immunostimulatory ability of huCD40LT-treated DC., (Copyright 1999 Academic Press.)

Alcohol sensing membranes coated on overhead transparency films for the continuous monitoring of ethanol, propanol and butanol are presented. Alcohol oxidation catalyzed by alcohol oxidase in conjunction with the fluorescence quenching reaction of oxygen-sensitive dye ion-pair, tris(4,7-diphenyl-1,10-phenanthroline) ruthenium(II) didodecylsulphate was chosen for the determination. Alcohol oxidase was immobilized covalently on a plasticized carboxylated poly(vinyl chloride) membrane and the oxygen-sensitive dye ion-pair was entrapped in the same membrane. The sensing membrane relates oxygen consumption, as a result of enzymatic oxidation, to alcohol concentration. Measurements have been performed in air-saturated alcohol standard solutions of pH 7.0. Storage stability, reproducibility and the effect of pH on sensing membrane performance have been studied in detail. The alcohol sensing membrane proposed here is simple to prepare and has a fairly rapid response time of <1 min. It has been successfully applied to the determination of the ethanol contents in various spirits.

The interactions between cisplatin and organic ions have been extensively investigated in animal models for the potential to reduce cisplatin cellular uptake and resultant nephrotoxicity. To further investigate the beneficial interaction clinically, we studied the effects of the organic cation, ranitidine, on the renal handling of cisplatin in children. In parallel, we examined the effects of cisplatin on the uptake kinetics of organic cations and anions by brush border membrane vesicles (BBMV) prepared from dog renal cortex. The results indicate that: 1) there is no measurable effect of ranitidine on renal clearance of cisplatin in children; and 2) BBMV uptake of anionic p-aminohippurate, but not cationic N-methylnicotinamide, is inhibited by cisplatin at concentrations of <1 mM. These findings suggest that cisplatin may not share transport systems with organic cations to a clinically significant degree. Assuming that renal tubular transport is a prerequisite for cisplatin nephrotoxicity, the lack of apparent kinetic interactions between cisplatin and organic cations may preclude clinical use of organic cations as a modality to prevent cisplatin nephrotoxicity.