ABSTRACT
BACKGROUND: Plasma phosphorylated-tau181 (p-tau181) represents a novel blood-based biomarker of Alzheimer's disease pathology. We explored clinicians' experience of the utility of plasma p-tau181 in Camden and Islington Memory Services. METHODS: Patients were identified by their clinician as appropriate for p-tau181. Their p-tau181 result was plotted on a reference range graph provided to clinicians. This was discussed with the patient at diagnostic feedback appointment. RESULTS: Twenty-nine participants' plasma p-tau181 samples were included (mean age 74 SD 8.5, 65% female). Nine clinicians participated in the study. Eighty-six percent of clinicians found the p-tau181 result to be helpful and in 93% of cases it was clearly understandable. The p-tau181 result was useful in making the diagnosis in 44% of cases. CONCLUSIONS: Plasma p-tau181 is a feasible test for use in memory services and acceptable to clinicians. Clinician feedback on utility in dementia diagnoses was mixed. Further work is required to provide education and training in understanding and interpreting ambiguity in biomarker results.
Subject(s)
Alzheimer Disease , Humans , Female , Aged , Male , Feasibility Studies , Educational Status , Alzheimer Disease/diagnosis , Reference ValuesABSTRACT
BACKGROUND: Elicitation of patients' preferences is an integral part of shared decision-making, the recommended approach for prostate cancer decision-making. Existing decision aids for this population often do not specifically focus on patients' preferences. Healium is a brief interactive web-based decision aid that aims to elicit patients' treatment preferences and is designed for a low health literate population. OBJECTIVE: This study used a randomized controlled trial to evaluate whether Healium, designed to target preference elicitation, is as efficacious as Healing Choices, a comprehensive education and decision tool, in improving outcomes for decision-making and emotional quality of life. METHODS: Patients diagnosed with localized prostate cancer who had not yet made a treatment decision were randomly assigned to the brief Healium intervention or Healing Choices, a decision aid previously developed by our group that serves as a virtual information center on prostate cancer diagnosis and treatment. Assessments were completed at baseline, 6 weeks, and 3 months post baseline, and included decisional outcomes (decisional conflict, satisfaction with decision, and preparation for decision-making), and emotional quality of life (anxiety/tension and depression), along with demographics, comorbidities, and health literacy. RESULTS: A total of 327 individuals consented to participate in the study (171 were randomized to the Healium intervention arm and 156 were randomized to Healing Choices). The majority of the sample was non-Hispanic (272/282, 96%), White (239/314, 76%), married (251/320, 78.4%), and was on average 62.4 (SD 6.9) years old. Within both arms, there was a significant decrease in decisional conflict from baseline to 6 weeks postbaseline (Healium, P≤.001; Healing Choices, P≤.001), and a significant increase in satisfaction with one's decision from 6 weeks to 3 months (Healium, P=.04; Healing Choices, P=.01). Within both arms, anxiety/tension (Healium, P=.23; Healing Choices, P=.27) and depression (Healium, P=.001; Healing Choices, P≤.001) decreased from baseline to 6 weeks, but only in the case of depression was the decrease statistically significant. CONCLUSIONS: Healium, our brief decision aid focusing on treatment preference elicitation, is as successful in reducing decisional conflict as our previously tested comprehensive decision aid, Healing Choices, and has the added benefit of brevity, making it the ideal tool for integration into the physician consultation and electronic medical record. TRIAL REGISTRATION: ClinicalTrials.gov NCT05800483; https://clinicaltrials.gov/study/NCT05800483.
Subject(s)
Decision Making , Prostatic Neoplasms , Male , Humans , Child , Decision Support Techniques , Quality of Life , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/therapy , EmotionsABSTRACT
Control over nanorod dimensions is critical to their application, requiring fast, robust characterisation of their volume and aspect ratio whilst in their working medium. Here, we present an extension of Nanoparticle Tracking Analysis which determines the aspect ratio of nanoparticles from the polarisation state of scattered light in addition to a hydrodynamic diameter from Brownian motion. These data, in principle, permit the determination of nanorod dimensions of any composition using Nanoparticle Tracking Analysis. The results are compared with transmission electron microscopy and show that this technique can additionally determine the aggregation state of the nanorod dispersion if single nanorod dimensions are determined with a complementary technique. We also show it is possible to differentiate nanoparticles of similar hydrodynamic diameter by their depolarised scattering. Finally, we assess the ability of the technique to output nanorod dimensions and suggest ways to further improve the approach. This technique will enable rapid characterisation of nanorods in suspension, which are important tools for nanotechnology.
ABSTRACT
INTRODUCTION: Tessier 30 facial cleft is a rare anomaly presenting in the soft and hard tissues over the central lower face. Owing to the rarity of cases and difficulty of treatment, there is no universally accepted surgical management strategy. The last comprehensive literature review of Tessier 30 clefts was in 1996. This report aims to update the literature to inform decision-making on treating Tessier 30 cases. METHODOLOGY: A literature search was performed. PubMed, SCOPUS, and OVID databases were searched. A total of 72 cases in 51 articles were analyzed, looking at demographics, extent of cleft, parent health, family history, procedures, follow-up, existence of other anomalies, and stages of repair. RESULTS: Surgeons are increasingly choosing to repair Tessier 30 defects in one rather than multiple stages. Of the 72 cases studied, only 31 had documented the completed repair of the cleft. All completed soft tissue only defects were repaired in 1 stage of repair (n = 11). Where both soft tissue and mandible was involved (n = 20), 55% (n = 11) had undergone 1-stage repair to address the Tessier 30 cleft. DISCUSSION: We argue that a single-stage approach is preferable to multistage. Primary mucogingivoperiosteoplasty should be undertaken in children at the time of management of the soft tissue cleft. The timing of this procedure should be in the latter half of the first year of life, as this is when mandibular symphyseal fusion normally occurs. We have suggested a treatment protocol and we hope that future case reports use our minimum data set.
Subject(s)
Cleft Lip , Plastic Surgery Procedures , Child , Cleft Lip/surgery , Clinical Protocols , Humans , Outcome Assessment, Health Care , Plastic Surgery Procedures/methods , Registries , Review Literature as TopicABSTRACT
BACKGROUND: Phosphoinositide-3-kinase-delta (PI3Kδ) inhibition is a promising therapeutic approach for inflammatory conditions due to its role in leucocyte proliferation, migration and activation. However, the effect of PI3Kδ inhibition on group 2 innate lymphoid cells (ILC2s) and inflammatory eosinophils remains unknown. Using a murine model exhibiting persistent airway inflammation we sought to understand the effect of PI3Kδ inhibition, montelukast and anti-IL5 antibody treatment on IL33 expression, group-2-innate lymphoid cells, inflammatory eosinophils, and goblet cell metaplasia. RESULTS: Mice were sensitised to house dust mite and after allowing inflammation to resolve, were re-challenged with house dust mite to re-initiate airway inflammation. ILC2s were found to persist in the airways following house dust mite sensitisation and after re-challenge their numbers increased further along with accumulation of inflammatory eosinophils. In contrast to montelukast or anti-IL5 antibody treatment, PI3Kδ inhibition ablated IL33 expression and prevented group-2-innate lymphoid cell accumulation. Only PI3Kδ inhibition and IL5 neutralization reduced the infiltration of inflammatory eosinophils. Moreover, PI3Kδ inhibition reduced goblet cell metaplasia. CONCLUSIONS: Hence, we show that PI3Kδ inhibition dampens allergic inflammatory responses by ablating key cell types and cytokines involved in T-helper-2-driven inflammatory responses.
Subject(s)
Class I Phosphatidylinositol 3-Kinases/metabolism , Eosinophils/immunology , Hypersensitivity/immunology , Inflammation/immunology , Interleukin-33/metabolism , Lymphocytes/immunology , Respiratory System/immunology , Acetates/therapeutic use , Animals , Antigens, Dermatophagoides/immunology , Class I Phosphatidylinositol 3-Kinases/antagonists & inhibitors , Cyclopropanes/therapeutic use , Cytokines/metabolism , Female , Goblet Cells/drug effects , Goblet Cells/pathology , Hypersensitivity/drug therapy , Inflammation/drug therapy , Interleukin-5/antagonists & inhibitors , Mice , Mice, Inbred BALB C , Pyroglyphidae , Quinolines/therapeutic use , Sulfides/therapeutic use , Th2 Cells/immunologyABSTRACT
Defective phagocytosis has been shown in chronic obstructive pulmonary disease (COPD) bronchoalveolar lavage and blood monocyte-derived macrophages. Phagocytic capabilities of sputum macrophages and neutrophils in COPD are unknown. We investigated phagocytosis in these cells from COPD patients and controls. Phagocytosis of Streptococcus pneumoniae or fluorescently labelled non-typeable Haemophilus influenzae (NTHi) by sputum macrophages and neutrophils was determined by gentamycin protection assay (COPD; n = 5) or flow cytometry in 14 COPD patients, 8 healthy smokers (HS) and 9 healthy never-smokers (HNS). Sputum macrophages and neutrophils were differentiated by adherence for the gentamycin protection assay or receptor expression (CD206 and CD66b, respectively), by flow cytometry. The effects of NTHi on macrophage expression of CD206 and CD14 and neutrophil expression of CD16 were determined by flow cytometry. There was greater uptake of S. pneumoniae [~10-fold more colony-forming units (CFU)/ml] by sputum neutrophils compared to macrophages in COPD patients. Flow cytometry showed greater NTHi uptake by neutrophils compared to macrophages in COPD (67 versus 38%, respectively) and HS (61 versus 31%, respectively). NTHi uptake by macrophages was lower in HS (31%, p = 0.019) and COPD patients (38%, p = 0.069) compared to HNS (57%). NTHi uptake by neutrophils was similar between groups. NTHi exposure reduced CD206 and CD14 expression on macrophages and CD16 expression on neutrophils. Sputum neutrophils showed more phagocytic activity than macrophages. There was some evidence that bacterial phagocytosis was impaired in HS sputum macrophages, but no impairment of neutrophils was observed in HS or COPD patients. These results highlight the relative contributions of neutrophils and macrophages to bacterial clearance in COPD.
Subject(s)
Haemophilus influenzae/immunology , Macrophages/immunology , Neutrophils/immunology , Phagocytosis , Pulmonary Disease, Chronic Obstructive/immunology , Sputum/immunology , Streptococcus mutans/immunology , Adult , Aged , Antigens, CD/immunology , Female , Flow Cytometry , Humans , Macrophages/microbiology , Male , Middle Aged , Neutrophils/microbiology , Pulmonary Disease, Chronic Obstructive/microbiology , Sputum/microbiologyABSTRACT
Herein we demonstrate the prowess of the 3D electron diffraction approach by unveiling the structure of terrylene, the third member in the series of peri-condensed naphthalene analogues, which has eluded structure determination for 65â years. The structure was determined by direct methods using electron diffraction data and corroborated by dispersion-inclusive density functional theory optimizations. Terrylene crystalizes in the monoclinic space group P21 /a, arranging in a sandwich-herringbone packing motif, similar to analogous compounds. Having solved the crystal structure, we use many-body perturbation theory to evaluate the excited-state properties of terrylene in the solid-state. We find that terrylene is a promising candidate for intermolecular singlet fission, comparable to tetracene and rubrene.
ABSTRACT
Introducing heterostructures to graphitic carbon nitrides (g-C3N4) can improve the activity of visible-light-driven catalysts for the efficient treatment of multiple toxic pollutants in water. Here, we report for the first time that a complex material can be constructed from oxygen-doped g-C3N4 and a MIL-53(Fe) metal-organic framework using facile hydrothermal synthesis and recycled polyethylene terephthalate from plastic waste. The novel multi-walled nanotube structure of the O-g-C3N4/MIL-53(Fe) composite, which enables the unique interfacial charge transfer at the heterojunction, showed an obvious enhancement in the separation efficiency of the photochemical electron-hole pairs. This resulted in a narrow bandgap energy (2.30 eV, compared to 2.55 eV in O-g-C3N4), high photocurrent intensity (0.17 mA cm-2, compared to 0.12 mA cm-2 and 0.09 mA cm-2 in MIL-53(Fe) and O-g-C3N4, respectively) and excellent catalytic performance in the photodegradation of anionic azo dyes (95% for RR 195 and 99% for RY 145 degraded after 4 h, and only a minor change in the efficiency observed after four consecutive tests). These results demonstrate the development of new catalysts made from waste feedstocks that show high stability, ease of fabrication and can operate in natural light for environmental remediation.
ABSTRACT
OBJECTIVES: Prostate cancer (PCa) survivors report poor physical functioning alongside negative psychological outcomes as they cope with treatment side effects and practical concerns after treatment completion. This study evaluated PROGRESS, a web-based intervention designed to improve adaptive coping among PCa survivors. METHODS: Localized PCa patients (N = 431) within one year of treatment completion were randomized to receive educational booklets or PROGRESS + educational booklets. Surveys completed at baseline, 1-, 3-, and 6-months assessed patient characteristics; functional quality of life and coping (primary outcomes); and psychosocial outcomes (e.g., self-efficacy, marital communication; secondary outcomes). Intent-to-treat and as-treated analyses were completed to assess change in outcomes from baseline to 6 months using linear mixed effects regression models. RESULTS: In the intent-to-treat analyses, participants randomized to the intervention group had improved diversion coping (i.e., healthy redirection of worrying thoughts about their cancer), but more difficulties in marital communication (ps < 0.05). However, PROGRESS usage was low among those randomized to the intervention group (38.7%). The as-treated analyses found PROGRESS users reported fewer practical concerns but had worse positive coping compared to PROGRESS non-users (ps < 0.05). CONCLUSIONS: The findings suggest PROGRESS may improve certain aspects of adaptive coping among PCa survivors that use the website, but does not adequately address the remaining coping and psychosocial domains. Additional research is needed to better understand the gaps in intervention delivery contributing to low engagement and poor improvement across all domains of functional quality of life and adaptive coping.
Subject(s)
Cancer Survivors , Internet-Based Intervention , Prostatic Neoplasms , Adaptation, Psychological , Humans , Male , Prostatic Neoplasms/therapy , Quality of Life , SurvivorsABSTRACT
BACKGROUND, CONTEXT AND PURPOSE: In spite of the mixed evidence for their impact, survivorship Care Plans (SCPs) are recommended to enhance quality of care for cancer survivors. Data on the feasibility of SCPs in bladder cancer (BC) is sparse. Using a mixed-methods approach, this study describes the iterative development, acceptability and feasibility of BC specific SCP (BC-SCP) in clinical settings. METHODS: In Phase I, we developed the BC-SCP. In Phase II, we conducted four focus groups with 19 patients and 15 providers to examine its acceptability and usability challenges. Data analyses using the Atlas.ti program, informed refinement of the BC-SCP. In Phase III, we conducted feasibility testing of the refined BC-SCP with 18 providers from 12 health-centers. An encounter survey was completed after each assessment to examine the feasibility of the BC-SCP. Chi-square and Fisher Exact tests were used for comparative analyses. RESULTS: During phase I, we observed high patient and provider acceptability of the BC-SCP and substantial engagement in improving its content, design, and structure. In Phase II, providers completed 59 BC-SCPs. Mean time for BC-SCP completion was 12.3 min. Providers reported that BC-SCP content was clear, did not hamper clinic flow and was readily completed with easy-to-access information. Comparative analyses to examine differences in SCP completion time by patient clinico-demographic characteristics and provider type revealed no significant differences. CONCLUSIONS: Our BC-SCP has clinical relevance, and can be used in an active practice setting. However, considerable progress will be necessary to achieve implementation of and sharing the BC-SCP with patients and care providers, particularly within the electronic medical record. In summary, BC-SCPs are essential to improve the follow up care of BC survivors. Clinical resources are required to ensure appropriate implementation of BC-SCPs. TRIAL REGISTRATION: Study HUM00056082.
Subject(s)
Cancer Survivors/psychology , Health Personnel/psychology , Patient Care Planning/organization & administration , Survivorship , Urinary Bladder Neoplasms/therapy , Aged , Cancer Survivors/statistics & numerical data , Feasibility Studies , Female , Focus Groups , Health Care Surveys , Health Personnel/statistics & numerical data , Humans , Male , Middle Aged , Patient Acceptance of Health Care/statistics & numerical data , Qualitative ResearchABSTRACT
This study aims to describe the acceptability and feasibility of an educational and training experiential intervention (ETEI) we developed to enhance muscle invasive bladder cancer (MIBC) patients with treatment decision-making and post-operative self-care. Twenty-five patients were randomized to a control group (N = 8) or ETEI group (N = 17). ETEI group participated in a nurse-led session on MIBC education. The control group received diet and nutrition education. Study questionnaires were completed at baseline and at 1-month post-intervention. Our results showed acceptable recruitment (58%) and retention rates (68%). The ETEI group reported increased knowledge (82% vs. 50%), improved decisional support (64% vs. 50%), improved communication (73% vs. 50%), and increased confidence in treatment decisions (73% vs. 50%) compared to the control group. Patients in the control group reported improved diet (50% v. 27%) as well as maintaining a healthy lifestyle (67% vs. 45%) compared to the ETEI group. Patients in the ETEI group reported a significant decrease in cancer worries and increases in self-efficacy beliefs over time compared to the control group. The ETEI was feasible, acceptable, and showed a potential for inducing desired changes in cancer worries and efficacy beliefs.
Subject(s)
Decision Making , Muscle Neoplasms/therapy , Patient Education as Topic/methods , Patient Participation/statistics & numerical data , Self Care/methods , Self Care/psychology , Urinary Bladder Neoplasms/therapy , Aged , Early Intervention, Educational , Feasibility Studies , Female , Humans , Male , Muscle Neoplasms/psychology , Prognosis , Self Efficacy , Surveys and Questionnaires , Urinary Bladder Neoplasms/psychologyABSTRACT
Orthocetamol is a regioisomer of the well-known pain medication paracetamol and a promising analgesic and an anti-arthritic medicament itself. However, orthocetamol cannot be grown as single crystals suitable for X-ray diffraction, so its crystal structure has remained a mystery for more than a century. Here, we report the ab-initio structure determination of orthocetamol obtained by 3D electron diffraction, combining a low-dose acquisition method and a dedicated single-electron detector for recording the diffracted intensities. The structure is monoclinic, with a pseudo-tetragonal cell that favors multiple twinning on a scale of a few tens of nanometers. The successful application of 3D electron diffraction to orthocetamol introduces a new gold standard of total structure solution in all cases where X-ray diffraction and electron-microscope imaging methods fail.
Subject(s)
Acetaminophen/chemistry , Electrons , Acetaminophen/analogs & derivatives , Crystallization , Models, Molecular , Molecular Structure , Particle Size , Solubility , Surface Properties , X-Ray DiffractionABSTRACT
The force-extension behaviour of synthesized double-stranded DNAs (dsDNAs) designed to have 2.1% or 6.6% of the thymine bases alkyne functionalized was studied using near infrared (NIR) optical tweezers. Measurements were carried out on substrates with and without flurophores covalently attached to the alkyne moiety over an extended force range (F=0-70 pN) and results were compared to those obtained from an unmodified control. In accordance with earlier work [1] (measured over a force range F=0-5 pN), the force-extension of the dsDNA containing 2.1% modified-bases agreed well with that of the control. By contrast, the force-extension of the dsDNA containing 6.6% modified-bases showed an increasing deviation from that of the control as the dsDNA extension approached the molecule's contour length. These results indicate that incorporating alkyne functionalized bases can modify the mechanical properties of the dsDNA and that degree of functionalization should be carefully considered if a fluorescent mechanical analogue is required. A discrepancy between 1) the control dsDNA force-extension measured in Ref. [1] and that measured here and 2) dsDNA extensions carried out on the same duplex at different laser powers was noted; this was attributed to beam heating by the NIR trapping laser which was estimated to raise the local temperature at the optical traps by ΔT≈10-15°C.
Subject(s)
Alkynes/chemistry , DNA/chemistry , Optical Tweezers , Elastic Modulus , Infrared Rays , Nucleic Acid Conformation , Stress, Mechanical , Tensile StrengthABSTRACT
PURPOSE: Prostate cancer patients who have undergone androgen deprivation therapy (ADT) may experience cognitive impairment, yet there is an unmet need for nonpharmacological interventions to address cognitive impairment in this population. This study examines the feasibility, acceptability, and preliminary efficacy of a home-based computerized cognitive training (CCT) program to treat cancer-related cognitive impairment. METHODS: Sixty men who had received ≥ 3 months of ADT were screened for at least mild cognitive or neurobehavioral impairment and randomized to 8 weeks of CCT or usual care. Follow-up assessments occurred immediately post-intervention or equivalent (T2) and 8 weeks later (T3). The acceptability of CCT was also assessed. RESULTS: Feasibility:A priori feasibility thresholds were partially met (i.e., randomization rate > 50%, retention rate > 70% excluding CCT drop-outs, but < 70% for intent-to-treat). Acceptability: Participants were mostly satisfied with CCT and found it somewhat enjoyable, though barriers to uptake existed. Preliminary efficacy: Linear mixed models indicated significant time by group effects favorable to CCT in reaction time (p = .01), but unfavorable to CCT in verbal and visual memory (ps < .05). Memory was temporarily suppressed in the CCT group at T2, but normalized by T3. There was no effect of CCT on self-reported cognitive functioning, neurobehavioral functioning, nor quality of life. CONCLUSIONS: This study provides tentative support for the feasibility and acceptability of CCT to treat mild cognitive impairment in ADT patients. CCT had a beneficial effect on reaction time, but temporarily suppressed memory. CCT's benefits may be limited to a narrow area of functioning. Larger-scale studies are needed.
Subject(s)
Androgen Antagonists/therapeutic use , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/therapy , Computer-Assisted Instruction/methods , Prostatic Neoplasms/drug therapy , Psychological Techniques , Aged , Antineoplastic Agents, Hormonal/therapeutic use , Cognition/drug effects , Cognition Disorders/chemically induced , Cognition Disorders/therapy , Feasibility Studies , Humans , Male , Memory/drug effects , Middle Aged , Pilot Projects , Prostatic Neoplasms/psychology , Quality of LifeABSTRACT
PURPOSE: We studied recurrence-free survival after partial vs radical nephrectomy for clinical stage T1 renal cell carcinoma in all patients and in those up staged to pathological stage T3a. MATERIALS AND METHODS: We retrospectively reviewed the records of 1,250 patients who underwent partial or radical nephrectomy for clinically localized T1 renal cell carcinoma between 2006 and 2014. Recurrence-free survival was estimated using the Kaplan-Meier method and evaluated as a function of nephrectomy type with the log rank test and Cox models, adjusting for clinical, radiological and pathological characteristics. RESULTS: A total of 86 recurrences (7%) were observed during a median followup of 37 months. No difference in recurrence-free survival between partial and radical nephrectomy was found among all clinical stage T1 renal cell carcinomas. T3a up staging was noted in 140 patients (11%) and recurrent disease was observed in 44 (31.4%) during a median followup of 38 months. Among up staged T3a cases partial nephrectomy was associated with shorter recurrence-free survival compared to radical nephrectomy on univariable analysis (recurrence HR 2.04, 95% CI 1.12-3.68, p = 0.019) and multivariable analysis (recurrence HR 5.39, 95% CI 1.94-14.9, p = 0.001). CONCLUSIONS: In a subgroup of patients clinically staged T1 renal cell carcinoma will be pathologically up staged to T3a. Among these patients those who undergo partial nephrectomy appear to have inferior recurrence-free survival relative to those who undergo radical nephrectomy.
Subject(s)
Carcinoma, Renal Cell/surgery , Kidney Neoplasms/surgery , Neoplasm Recurrence, Local/epidemiology , Nephrectomy/adverse effects , Aged , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Disease-Free Survival , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/prevention & control , Neoplasm Staging , Nephrectomy/methods , Patient Selection , Retrospective StudiesABSTRACT
Anodophilic bacteria have the ability to generate electricity in microbial fuel cells (MFCs) by extracellular electron transfer to the anode. We investigated the anode-specific responses of Shewanella oneidensis MR-1, an exoelectroactive Gammaproteobacterium, using for the first time iTRAQ and 2D-LC MS/MS driven membrane proteomics to compare protein abundances in S. oneidensis when generating power in MFCs, and growing in a continuous culture. The regulated dataset produced was enriched in membrane proteins. Proteins shown to be more abundant in anaerobic electroactive anodic cells included efflux pump TolC and an uncharacterised tetratricopeptide repeat (TPR) protein, whilst the TonB2 system and associated uncharacterised proteins such as TtpC2 and DUF3450 were more abundant in microaerobic planktonic cells. In order to validate the iTRAQ data, the functional role for TolC was examined using a δTolC knockout mutant of S. oneidensis. Possible roles for the uncharacterised proteins were identified using comparative bioinformatics. We demonstrate that employing an insoluble extracellular electron acceptor requires multiple proteins involved in cell surface properties. All MS and processed data are available via ProteomeXchange with identifier PXD004090.
Subject(s)
Bioelectric Energy Sources , Proteomics/methods , Shewanella/genetics , Biofilms , Electricity , Electrodes , Electron Transport , Electrons , Shewanella/chemistry , Tandem Mass SpectrometryABSTRACT
Measurements of the electrostatic force with separation between a fixed and an optically trapped colloidal particle are examined with experiment, simulation and analytical calculation. Non-Gaussian Brownian motion is observed in the position of the optically trapped particle when particles are close and traps weak. As a consequence of this motion, a simple least squares parameterization of direct force measurements, in which force is inferred from the displacement of an optically trapped particle as separation is gradually decreased, contains forces generated by the rectification of thermal fluctuations in addition to those originating directly from the electrostatic interaction between the particles. Thus, when particles are close and traps weak, simply fitting the measured direct force measurement to DLVO theory extracts parameters with modified meanings when compared to the original formulation. In such cases, however, physically meaningful DLVO parameters can be recovered by comparing the measured non-Gaussian statistics to those predicted by solutions to Smoluchowski's equation for diffusion in a potential.
Subject(s)
Colloids/chemistry , Motion , Optical Tweezers , Static Electricity , DiffusionABSTRACT
Asthma is increasing globally and current treatments only manage a proportion of patients. There is an urgent need to develop new therapies. Lymphocytes are thought to play a central role in the pathophysiology of asthma through the production of inflammatory mediators. This is thought to be via the transcription factor NFAT which in turn can be activated through Ca(2+) release-activated Ca(2+) (CRAC) channels. The aim of this work was to investigate the role of CRAC in clinical and pre-clinical models of allergic asthma. Initial data demonstrated that the NFAT pathway is increased in stimulated lymphocytes from asthmatics. To confirm a role for the channel we showed that a selective inhibitor, Synta 66, blocked mediator production from lymphocytes. Synta 66 inhibited CD2/3/28 induced IL-2, IL-7, IL-13 & IFNΥ in a concentration-dependent manner in healthy and severe asthma donors, with over 60% inhibition observed for all cytokines. NFAT pathway was also increased in a pre-clinical asthma model. In this model we have demonstrated that CRAC played a central role in the airway inflammation and late asthmatic response (LAR). In conclusion, our data provides evidence that suggests targeting CRAC channels could be of therapeutic benefit for asthma sufferers.
Subject(s)
Asthma/metabolism , Calcium Channels/metabolism , Adult , Allergens/toxicity , Animals , Asthma/pathology , Bronchoalveolar Lavage Fluid/cytology , Calcium Channels/drug effects , Cells, Cultured , Cytokines/biosynthesis , Dose-Response Relationship, Drug , Female , Humans , In Vitro Techniques , Lung/pathology , Lymphocytes/drug effects , Lymphocytes/metabolism , Male , Middle Aged , NFATC Transcription Factors/metabolism , Neutrophils/drug effects , Neutrophils/metabolism , RatsABSTRACT
PURPOSE: Although improvements in perioperative care have decreased surgical morbidity after radical cystectomy for muscle invasive bladder cancer, treatment side effects still have a negative impact on patient quality of life. We examined unmet patient needs along the illness trajectory. MATERIALS AND METHODS: A total of 30 patients (26.7% women) treated with cystectomy and urinary diversion for muscle invasive bladder cancer participated in the study. Patients were recruited from the Department of Urology at Mount Sinai and through advertisements on the Bladder Cancer Advocacy Network (BCAN) website between December 2011 and September 2012. Data were collected at individual interviews, which were audiotaped and transcribed. Transcribed data were quantitatively analyzed to explore key unmet needs. RESULTS: At diagnosis unmet informational needs were predominant, consisting of insufficient discussion of certain topics, including urinary diversion options and their side effects, self-care, the recovery process and medical insurance. Unmet psychological needs related to depression, and worries about changes in body image and sexual function were reported. Postoperative unmet needs revolved around medical needs (eg pain and bowel dysfunction) and instrumental needs (eg need of support for stomal appliances, catheters and incontinence). During survivorship (ie 6 to 72 months postoperatively) unmet needs centered around psychological support (ie depression, poor body image and sexual dysfunction) and instrumental support (eg difficulty adjusting to changes in daily living). CONCLUSIONS: Meeting patient needs is imperative to ensure adequate patient involvement in health care and enhance postoperative quality of life. An effective support provision plan should follow changes in patient needs.