ABSTRACT
BACKGROUND/PURPOSE: Diffuse reflectance spectroscopy (DRS) is a noninvasive optical technology characterized by relatively low system cost and high efficiency. In our previous study, we quantified the relative concentration of collagen for the individual keloid patient. However, no actual value of collagen concentration can prove the reliability of collagen detection by our DRS system. METHODS: Skin-mimicking phantoms were prepared using different collagen and coffee concentrations, and their chromophore concentrations were quantified using the DRS system to analyze the influence of collagen and other chromophores. Moreover, we used the animal study to compare the DRS system with the collagen evaluation of biopsy section by second-harmonic generation (SHG) microscopy at four different skin parts. RESULTS: In the phantom study, the result showed that coffee chromophore did not severely interfere with collagen concentration recovery. In the animal study, a positive correlation (r=.902) between the DRS system and collagen evaluation with SHG microscopy was found. CONCLUSIONS: We have demonstrated that the DRS system can quantify the actual values of collagen concentration and excluded the interference of other chromophores in skin-mimicking phantoms. Furthermore, a high positive correlation was found in the animal study with SHG microscopy. We consider that the DRS is a potential technique and can evaluate skin condition objectively.
Subject(s)
Collagen/analysis , Skin/chemistry , Animals , Biopsy , Humans , Male , Microscopy , Phantoms, Imaging , Skin/pathology , Spectrum Analysis/methods , Swine , Swine, MiniatureABSTRACT
BACKGROUND AND PURPOSE: Target volume definitions for radiotherapy in pancreatic ductal adenocarcinoma (PDAC) vary substantially. Some groups aim to treat the primary tumor only, whereas others include elective lymph nodes (eLNs). eLNs close to the primary tumor are often included unintentionally within the treatment volume, depending on the respective treatment philosophies. We aimed to measure the percentages of anatomical coverage of eLNs by comparing four different contouring guidelines. PATIENTS AND METHODS: Planning target volumes (PTVs) were contoured using planning computed tomography (CT) scans of 11Ā patients with PDAC based on the Oxford, RTOG (Radiation Therapy Oncology Group), Michigan, and SCALOP (Selective Chemoradiation in Advanced Localised Pancreatic Cancer trial) guidelines. Clinical target volumes (CTVs) included the peripancreatic, para-aortic, paracaval, celiac trunk, superior mesenteric, and portal vein lymph node areas. Volumetric comparisons of the coverage of all eLN regions were conducted to illustrate the differences between the four contouring strategies. RESULTS: The PTV sizes of the RTOG and Oxford guidelines were comparable. The SCALOP and Michigan PTV sizes were similar to each other and significantly smaller than the RTOG and Oxford PTVs. A large variability of eLN coverage was found for the various subregions according to the respective contouring strategies. CONCLUSION: This is the first study to directly compare the percentage of anatomical coverage of eLNs according to four PTVs in the same patient cohort. Potential practical consequences are discussed in detail.
Subject(s)
Carcinoma, Pancreatic Ductal/diagnosis , Carcinoma, Pancreatic Ductal/radiotherapy , Imaging, Three-Dimensional/standards , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/radiotherapy , Practice Guidelines as Topic , Tomography, X-Ray Computed/standards , Carcinoma, Pancreatic Ductal/secondary , Germany , Humans , Lymphatic Metastasis , Reproducibility of Results , Sensitivity and Specificity , Tumor BurdenABSTRACT
AIMS: Irradiation of pelvic bone marrow (PBM) at the level of the typical low dose bath of intensity-modulated radiotherapy delivery (10-20 Gy) is associated with an increased risk of haematological toxicity, particularly when combined with concurrent chemotherapy. Although sparing of the whole of the PBM at a 10-20 Gy dose level is unachievable, it is known that PBM is divided into haematopoietically active and inactive regions that are identifiable based on the threshold uptake of [18F]-fluorodeoxyglucose (FDG) seen on positron emission tomography-computed tomography (PET-CT). In published studies to date, the definition of active PBM widely used is that of a standardised uptake value (SUV) greater than the mean SUV of the whole PBM prior to the start of chemoradiation. These studies include those looking at developing an atlas-based approach to contouring active PBM. Using baseline and mid-treatment FDG PET scans acquired as part of a prospective clinical trial we sought to determine the suitability of the current definition of active bone marrow as representative of differential underlying cell physiology. MATERIALS AND METHODS: Active and inactive PBM were contoured on baseline PET-CT and using deformable registration mapped onto mid-treatment PET-CT. Volumes were cropped to exclude definitive bone, voxel SUV extracted and the change between scans calculated. Change was compared using Mann-Whitney U testing. RESULTS: Active and inactive PBM were shown to respond differentially to concurrent chemoradiotherapy. The median absolute response of active PBM for all patients was -0.25 g/ml, whereas the median inactive PBM response was -0.02 g/ml. Significantly, the inactive PBM median absolute response was shown to be near zero with a relatively unskewed distribution (0.12). CONCLUSIONS: These results would support the definition of active PBM as FDG uptake greater than the mean of the whole structure as being representative of underlying cell physiology. This work would support the development of atlas-based approaches published in the literature to contour active PBM based on the current definition as being suitable.
Subject(s)
Fluorodeoxyglucose F18 , Positron Emission Tomography Computed Tomography , Humans , Positron Emission Tomography Computed Tomography/methods , Bone Marrow/diagnostic imaging , Bone Marrow/radiation effects , Prospective Studies , Positron-Emission Tomography/methods , Chemoradiotherapy/methods , RadiopharmaceuticalsABSTRACT
AIMS/HYPOTHESIS: Ubiquitin C-terminal hydrolase L1 (UCHL1) is associated with neurodegenerative diseases and has been suggested to have roles in pancreatic beta cells. Our proteomic analysis revealed that UCHL1 was the most increased protein in MIN6 cells exposed to palmitate. The present study used a genetic loss-of-function model to test the hypothesis that UCHL1 is required for normal beta cell function and fate under lipotoxic conditions. METHODS: Human islets, mouse islets and MIN6 cells were used to analyse UCHL1 protein levels and regulation of UCHL1 by palmitate. The levels of free mono-ubiquitin and poly-ubiquitinated proteins were assessed. Gracile axonal dystrophy (GAD) mutant mice lacking UCHL1 were fed a normal or lipotoxic high-fat diet. Glucose tolerance, insulin tolerance and insulin secretion were assessed in vivo. Beta cell death and proliferation were assessed by TUNEL and proliferating cell nuclear antigen (PCNA) staining. Insulin secretion, calcium signalling, endoplasmic reticulum (ER) stress, apoptosis and SNARE protein levels were assessed in vitro. RESULTS: UCHL1 protein, which was highly specific to beta cells, was increased by palmitate at basal glucose, but not in the context of hyperglycaemia associated with frank diabetes. Although islet development and function were initially normal in Uchl1 (-/-) mice, a 4-week high-fat diet caused glucose intolerance and impaired insulin secretion. Uchl1 (-/-) mice had increased ER stress and beta cell apoptosis. The levels of SNARE proteins were dysregulated in Uchl1 (-/-) islets. Palmitate-stimulated vesicle-associated membrane protein 2 (VAMP2) ubiquitination was modulated by a chemical UCHL1 inhibitor. CONCLUSIONS/INTERPRETATION: Together, these data suggest that UCHL1 has essential functional and anti-apoptotic roles in beta cells under stress conditions associated with lipotoxicity.
Subject(s)
Apoptosis , Endoplasmic Reticulum Stress , Insulin-Secreting Cells/metabolism , Insulin/metabolism , Palmitic Acid/adverse effects , Ubiquitin Thiolesterase/metabolism , Animals , Apoptosis/drug effects , Cell Line , Cell Proliferation/drug effects , Enzyme Inhibitors/pharmacology , Humans , Insulin Secretion , Insulin-Secreting Cells/cytology , Insulin-Secreting Cells/drug effects , Isoenzymes/antagonists & inhibitors , Isoenzymes/metabolism , Male , Mice , Mice, Neurologic Mutants , Neuroaxonal Dystrophies/metabolism , Neuroaxonal Dystrophies/pathology , RNA, Messenger/metabolism , SNARE Proteins/metabolism , Ubiquitin Thiolesterase/antagonists & inhibitors , Ubiquitin Thiolesterase/genetics , Ubiquitination/drug effects , Up-Regulation/drug effects , Vesicle-Associated Membrane Protein 2/metabolismABSTRACT
INTRODUCTION: Radiographer reporting is accepted practice in the UK. With a national shortage of radiographers and radiologists, artificial intelligence (AI) support in reporting may help minimise the backlog of unreported images. Modern AI is not well understood by human end-users. This may have ethical implications and impact human trust in these systems, due to over- and under-reliance. This study investigates the perceptions of reporting radiographers about AI, gathers information to explain how they may interact with AI in future and identifies features perceived as necessary for appropriate trust in these systems. METHODS: A QualtricsĀ® survey was designed and piloted by a team of UK AI expert radiographers. This paper reports the third part of the survey, open to reporting radiographers only. RESULTS: 86 responses were received. Respondents were confident in how an AI reached its decision (nĀ =Ā 53, 62%). Less than a third of respondents would be confident communicating the AI decision to stakeholders. Affirmation from AI would improve confidence (nĀ =Ā 49, 57%) and disagreement would make respondents seek a second opinion (nĀ =Ā 60, 70%). There is a moderate trust level in AI for image interpretation. System performance data and AI visual explanations would increase trust. CONCLUSIONS: Responses indicate that AI will have a strong impact on reporting radiographers' decision making in the future. Respondents are confident in how an AI makes decisions but less confident explaining this to others. Trust levels could be improved with explainable AI solutions. IMPLICATIONS FOR PRACTICE: This survey clarifies UK reporting radiographers' perceptions of AI, used for image interpretation, highlighting key issues with AI integration.
Subject(s)
Radiology , Artificial Intelligence , Clinical Competence , Humans , Radiologists , Radiology/education , United KingdomABSTRACT
BACKGROUND: It is important to understand whether older people are admitted into residential care with existing dental diseases or their oral health deteriorates while residing in residential care. There is, however, little research available exploring the oral health status of people newly admitted into residential care. Understanding this disease trend would lead to effective prevention and treatment strategies to be trialled and implemented prior to admission. In this cross-sectional study, we hypothesize that older people with one or more natural teeth might have poor oral health prior to admission to residential care. METHOD: The study was carried out using the de-identified oral health assessment database of an established domiciliary oral health care program in metropolitan New South Wales, Australia. Four hundred and nine participants with mean participant age of 85.56 years from 13 facilities from 2015 to 2018 fulfilled the inclusion criteria for this study. CONCLUSION: This study confirmed that dentate, newly admitted residents to residential care had pre-existing dental problems and oral health concerns. Almost half of the newly admitted residents had an unsatisfactory oral cleanliness score when examined in their residential care setting.
Subject(s)
Mouth, Edentulous , Oral Health , Aged , Aged, 80 and over , Cross-Sectional Studies , Health Status , Hospitalization , Humans , New South Wales/epidemiologyABSTRACT
INTRODUCTION: Artificial intelligence (AI) has started to be increasingly adopted in medical imaging and radiotherapy clinical practice, however research, education and partnerships have not really caught up yet to facilitate a safe and effective transition. The aim of the document is to provide baseline guidance for radiographers working in the field of AI in education, research, clinical practice and stakeholder partnerships. The guideline is intended for use by the multi-professional clinical imaging and radiotherapy teams, including all staff, volunteers, students and learners. METHODS: The format mirrored similar publications from other SCoR working groups in the past. The recommendations have been subject to a rapid period of peer, professional and patient assessment and review. Feedback was sought from a range of SoR members and advisory groups, as well as from the SoR director of professional policy, as well as from external experts. Amendments were then made in line with feedback received and a final consensus was reached. RESULTS: AI is an innovative tool radiographers will need to engage with to ensure a safe and efficient clinical service in imaging and radiotherapy. Educational provisions will need to be proportionately adjusted by Higher Education Institutions (HEIs) to offer the necessary knowledge, skills and competences for diagnostic and therapeutic radiographers, to enable them to navigate a future where AI will be central to patient diagnosis and treatment pathways. Radiography-led research in AI should address key clinical challenges and enable radiographers co-design, implement and validate AI solutions. Partnerships are key in ensuring the contribution of radiographers is integrated into healthcare AI ecosystems for the benefit of the patients and service users. CONCLUSION: Radiography is starting to work towards a future with AI-enabled healthcare. This guidance offers some recommendations for different areas of radiography practice. There is a need to update our educational curricula, rethink our research priorities, forge new strong clinical-academic-industry partnerships to optimise clinical practice. Specific recommendations in relation to clinical practice, education, research and the forging of partnerships with key stakeholders are discussed, with potential impact on policy and practice in all these domains. These recommendations aim to serve as baseline guidance for UK radiographers. IMPLICATIONS FOR PRACTICE: This review offers the most up-to-date recommendations for clinical practitioners, researchers, academics and service users of clinical imaging and therapeutic radiography services. Radiography practice, education and research must gradually adjust to AI-enabled healthcare systems to ensure gains of AI technologies are maximised and challenges and risks are minimised. This guidance will need to be updated regularly given the fast-changing pace of AI development and innovation.
Subject(s)
Artificial Intelligence , Radiology , Allied Health Personnel , Ecosystem , Humans , RadiographyABSTRACT
AIMS: The use of diffusion-weighted magnetic resonance imaging (DW-MRI) as a prognostic marker of treatment response would enable early individualisation of treatment. We aimed to quantify the changes in mean apparent diffusion coefficient (ΔADCmean) between a DW-MRI at diagnosis and on fraction 8-10 of chemoradiotherapy (CRT) as a biomarker for cellularity, and correlate these with anal squamous cell carcinoma recurrence. MATERIALS AND METHODS: This prospective study recruited patients with localised anal cancer between October 2014 and November 2017. DW-MRI was carried out at diagnosis and after fraction 8-10 of radical CRT. A region of interest was delineated for all primary tumours and any lymph nodes >2 cm on high-resolution T2-weighted images and propagated to the ADC map. Routine clinical follow-up was collected from Nation Health Service electronic systems. RESULTS: Twenty-three of 29 recruited patients underwent paired DW-MRI scans. Twenty-six regions of interest were delineated among the 23 evaluable patients. The median (range) tumour volume was 13.6 cm3 (2.8-84.9 cm3). Ten of 23 patients had lesions with ΔADCmean ≤ 20%. With a median follow-up of 41.2 months, four patients either failed to have a complete response to CRT or subsequently relapsed. Three of four patients with disease relapse had lesions demonstrating ΔADCmean <20%, the other patient with persistent disease had ΔADCmean of 20.3%. CONCLUSIONS: We demonstrated a potential correlation between patients with ΔADCmean <20% and disease relapse. Further investigation of the prognostic merit of DW-MRI change is needed in larger, prospective cohorts.
Subject(s)
Anus Neoplasms/pathology , Biomarkers, Tumor/analysis , Carcinoma, Squamous Cell/pathology , Chemoradiotherapy/methods , Neoplasm Recurrence, Local/pathology , Aged , Anus Neoplasms/diagnostic imaging , Anus Neoplasms/therapy , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/therapy , Diffusion Magnetic Resonance Imaging/methods , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/therapy , Prognosis , Prospective Studies , Tumor BurdenABSTRACT
AIMS: To investigate the potential role for a biological boost in anal cancer by assessing whether subvolumes of high 18F-fluorodeoxyglucose (FDG) avidity, identified at outset, are spatially consistent during a course of chemoradiotherapy (CRT). MATERIALS AND METHODS: FDG-positron emission tomography (FDG-PET) scans from 21 patients enrolled into the ART study (NCT02145416) were retrospectively analysed. In total, 29 volumes including both primary tumours and involved nodes >2 cm were identified. FDG-PET scans were carried out before treatment and on day 8 or 9 of CRT. FDG subvolumes were created using a percentage of maximum FDG avidity at thresholds of 34%, 40%, 50%, on the pre-treatment scans, and 70% and 80% on the subsequent scans. Both FDG-PET scans were deformably registered to the planning computed tomography scan. The overlap fraction and the vector distance were calculated to assess spatial consistency. FDG subvolumes for further investigation had an overlap fraction >0.7, as this has been defined in previous publications as a 'good' correlation. RESULTS: The median overlap fractions between the diagnostic FDG-PET subvolumes 34%, 40% and 50% of maximum standardised uptake value (SUVmax) and subsequent FDG-PET subvolumes of 70% of SUVmax were 0.97, 0.92 and 0.81. The median overlap fraction between the diagnostic FDG-PET subvolumes 34%, 40% and 50% and subsequent FDG-PET subvolumes of 80% were 1.00, 1.00 and 0.92. The median (range) vector distance values between diagnostic FDG-PET subvolumes 34%, 40% and 50% and subsequent FDG-PET subvolumes of 80% were 0.74 mm (0.19-2.94) 0.74 mm (0.19-3.39) and 0.71 mm (0.2-3.29), respectively. Twenty of 29 volumes (69.0%) achieved a thresholdĀ >Ā 0.7 between the FDG 50% subvolume on the diagnostic scan and the FDG 80% subvolume on the subsequent scan. CONCLUSION: FDG-avid subvolumes identified at baseline were spatially consistent during a course of CRT treatment. The subvolume of 50% of SUVmax on the pre-treatment scan could be considered as a potential target for dose escalation.
Subject(s)
Anus Neoplasms/diagnosis , Anus Neoplasms/radiotherapy , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/radiotherapy , Chemoradiotherapy/methods , Fluorodeoxyglucose F18/therapeutic use , Positron-Emission Tomography/methods , Aged , Female , Fluorodeoxyglucose F18/pharmacology , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
Exposure of adipocytes to arachidonic acid rapidly enhanced basal 2-deoxyglucose uptake, reaching maximal effect at approximately 8 hr. Insulin-stimulated 2-deoxyglucose uptake was not altered over the experimental period. While the short-term (2-h exposure) effect of arachidonic acid was negligibly influenced by cycloheximide, the enhancement of glucose transport by long-term (8-h) exposure to arachidonic acid was markedly decreased by the simultaneous presence of protein-synthesis inhibitors, implying that the short-term and long-term effects of arachidonic acid may involve distinct mechanisms. Immunoblot analysis revealed that 8-h but not 2-h exposure to arachidonic acid increased the content of the ubiquitous glucose transporter (GLUT1) in both total cellular and plasma membranes. The insulin-responsive glucose transporter (GLUT4), on the other hand, was not affected. Following 2-h exposure to arachidonic acid, kinetic studies indicated that the apparent Vmax of basal 2-deoxyglucose uptake was more than doubled, while the apparent Km for 2-deoxyglucose remained unchanged. Protein kinase C (PKC) depletion by pretreating cells with 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) for 24 h had little influence on the subsequent enhancing effect of arachidonic acid on 2-deoxyglucose uptake. In addition, PMA was able to stimulate 2-deoxyglucose uptake in arachidonic-acid-pretreated cells with similar increments as in non-treated cells. Thus, our data seem to suggest that arachidonic acid may enhance the intrinsic activity of GLUT1 by a PKC-independent mechanism.
Subject(s)
Adipocytes/metabolism , Arachidonic Acid/pharmacology , Monosaccharide Transport Proteins/metabolism , Muscle Proteins , Protein Kinase C/metabolism , 3T3 Cells , Adipocytes/drug effects , Animals , Anisomycin/pharmacology , Cycloheximide/pharmacology , Deoxyglucose/pharmacokinetics , Dose-Response Relationship, Drug , Glucose Transporter Type 1 , Glucose Transporter Type 4 , Insulin/pharmacology , Methionine/pharmacokinetics , Mice , Protein Synthesis Inhibitors/pharmacologyABSTRACT
A molecule with two immunoglobulin (Ig) domains cloned from Leishmania mexicana amazonensis was characterized to have a sequence homology to the Ig domains of an ICAM-like molecule telencephalin, cloned from the brain of mammals, as well as to the variable domains of human immunoglobulin lambda light chain. The molecule therefore appears to be an ICAM-like molecule as well as a member of the immunoglobulin superfamily. We thus named it ICAM-L for Leishmania ICAM. The gene was coamplified with the ribonucleotide reductase M(2) subunit gene responsible for hydroxyurea resistance from hydroxyurea (Hu)-resistant Leishmania variants. As expected, an increase of the ICAM-L protein as well as an increase of the specific ICAM-L transcript of 2.1 kb was detected in the Hu-resistant variants with increasing doses of the drug used for resistance selection. Structurally, ICAM-L is more similar to the secretory adhesive molecules, such as 1Bgp and the link protein of the immunoglobulin superfamily, in that it lacks a transmembrane region and a GPI anchor sequence. Although ICAM-L was mainly localized in the nucleus of the parasite by confocal microscopy, however, detailed studies by electron microscopy and FACS analysis indicated that the protein was also localized on the surface of the parasite. The surface localization of the protein was furthered strengthened by the observations that anti-ICAM-L or ICAM-L itself can significantly block the binding of the parasite to macrophages. The blocking of the attachment of parasite to macrophages may indicate that ICAM-L functions as an intercellular adhesive molecule.
Subject(s)
Immunoglobulins/chemistry , Intercellular Adhesion Molecule-1/chemistry , Intercellular Adhesion Molecule-1/metabolism , Leishmania mexicana/genetics , Amino Acid Motifs , Amino Acid Sequence , Animals , Antibodies, Protozoan/immunology , Base Sequence , Cell Line , Cloning, Molecular , Disulfides/metabolism , Humans , Hydroxyurea/pharmacology , Immune Sera/immunology , Intercellular Adhesion Molecule-1/genetics , Intercellular Adhesion Molecule-1/immunology , Leishmania mexicana/drug effects , Leishmania mexicana/metabolism , Leishmania mexicana/ultrastructure , Leishmaniasis, Cutaneous/parasitology , Macrophages/parasitology , Mice , Microscopy, Immunoelectron , Molecular Sequence Data , Protein Transport , Protozoan Proteins/chemistry , Protozoan Proteins/genetics , Protozoan Proteins/immunology , Protozoan Proteins/metabolism , RNA, Protozoan/genetics , RNA, Protozoan/metabolism , Recombinant Fusion Proteins/biosynthesis , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/immunology , Recombinant Fusion Proteins/metabolism , Sequence Alignment , Sequence HomologyABSTRACT
Hantaviruses are found in widely scattered areas of the world and are transmitted by inhalation of virus-contaminated aerosols of rodent excreta. The present study was undertaken in Kuwait to investigate the serological evidence for hantavirus infection in rodents and humans. Sera were collected from 283 wild rodents and 183 human subjects (46 Kuwaitis and 137 non-Kuwaitis). The rodent sera were investigated for the presence of antibodies against the Seoul and Puumala strains of the hantaviruses by enzyme-linked immunosorbent assay and immunofluorescence technique using the virus-infected Vero E6 cells. The findings showed the presence of anti-hantavirus antibodies in seven out of the 283 (2.8%) rodents. Antibodies against the Seoul strain were present in six (2.1%) and against the Puumala strain in three (1%) rodents. Further, it was observed that three out of 84 (3.6%) of the Rattus norvegicus and four out of 174 (2.3%) Mus musculus had anti-hantavirus antibodies. Two rodents belonging to species Mus musculus had antibodies against both strains of the hantaviruses. Out of 183 human sera, 13 (7%) were positive for hantavirus antibodies. Among the Kuwaitis 5/46 (11%) and among the non-Kuwaitis 8/137 (6%) were positive for the hantavirus antibodies. Antibodies to both Puumala and Hantaan strains were detected in Kuwaitis as well as in non-Kuwaitis. Although no human case of hantavirus illness has yet been reported in Kuwait, the serological evidence of infection suggests a constant vigil.
Subject(s)
Antibodies, Viral/blood , Hantavirus Infections/diagnosis , Orthohantavirus/immunology , Rodent Diseases/diagnosis , Rodentia/virology , Adult , Aged , Animals , Hantavirus Infections/epidemiology , Hantavirus Infections/veterinary , Hantavirus Infections/virology , Humans , Kuwait/epidemiology , Middle Aged , Rats , Rodent Diseases/epidemiology , Rodent Diseases/virologyABSTRACT
Our laboratory has previously conducted a number of studies to determine the effects of chronic stress on the physiology and behavior of male rats. The present study was performed to extend these investigations to female rats. Female rats were chronically stressed using a behavioral paradigm of around-the-clock signalled intermittent foot shock in which some rats can pull a chain to avoid/escape shock (stress) while another group of rats is yoked to the first group (yoked-stress) and does not have control over shock termination. Control rats were never shocked but all groups lever pressed for food pellets on an FR1 schedule (one pellet per lever press). Daily vaginal samples were obtained for several weeks prior to stress onset and throughout the chronic stress period. After 14 days of stress, the experiment was terminated and morning blood samples were collected for hormonal assays. Stress transiently decreased lever pressing for food pellets and body weights, but both measures returned to prestress levels by day 14 of stress. Plasma adrenocorticotropic hormone (ACTH) concentrations were significantly elevated in the yoked-stress group compared to the other two groups, but there were no significant effects of 14 days of stress treatment on plasma corticosterone, prolactin, estradiol, or progesterone concentrations. There were no significant differences in estrous cycle length among experimental groups.
Subject(s)
Appetitive Behavior/physiology , Arousal/physiology , Estrus/physiology , Feeding Behavior/physiology , Hormones/blood , Stress, Psychological/complications , Adrenocorticotropic Hormone/blood , Animals , Corticosterone/blood , Electroshock , Escape Reaction/physiology , Estradiol/blood , Fear/physiology , Female , Male , Progesterone/blood , Prolactin/blood , Rats , Rats, Sprague-Dawley , Sex FactorsABSTRACT
Diabetes is associated with the death and dysfunction of insulin-producing pancreatic Ć-cells. In other systems, Musashi genes regulate cell fate via Notch signaling, which we recently showed regulates Ć-cell survival. Here we show for the first time that human and mouse adult islet cells express mRNA and protein of both Musashi isoforms, as well Numb/Notch/Hes/neurogenin-3 pathway components. Musashi expression was observed in insulin/glucagon double-positive cells during human fetal development and increased during directed differentiation of human embryonic stem cells (hESCs) to the pancreatic lineage. De-differentiation of Ć-cells with activin A increased Msi1 expression. Endoplasmic reticulum (ER) stress increased Msi2 and Hes1, while it decreased Ins1 and Ins2 expression, revealing a molecular link between ER stress and Ć-cell dedifferentiation in type 2 diabetes. These effects were independent of changes in Numb protein levels and Notch activation. Overexpression of MSI1 was sufficient to increase Hes1, stimulate proliferation, inhibit apoptosis and reduce insulin expression, whereas Msi1 knockdown had the converse effects on proliferation and insulin expression. Overexpression of MSI2 resulted in a decrease in MSI1 expression. Taken together, these results demonstrate overlapping, but distinct roles for Musashi-1 and Musashi-2 in the control of insulin expression and Ć-cell proliferation. Our data also suggest that Musashi is a novel link between ER stress and the compensatory Ć-cell proliferation and the loss of Ć-cell gene expression seen in specific phases of the progression to type 2 diabetes.
Subject(s)
Apoptosis , Diabetes Mellitus, Type 2/metabolism , Endoplasmic Reticulum Stress/physiology , Insulin-Secreting Cells/metabolism , Insulin/metabolism , Nerve Tissue Proteins/metabolism , RNA-Binding Proteins/metabolism , Activins/metabolism , Animals , Basic Helix-Loop-Helix Transcription Factors/metabolism , Cell Differentiation , Cell Proliferation , Cells, Cultured , Diabetes Mellitus, Type 2/pathology , Embryonic Stem Cells/cytology , Gene Expression Regulation , Homeodomain Proteins/metabolism , Humans , Mice , Nerve Tissue Proteins/antagonists & inhibitors , RNA-Binding Proteins/antagonists & inhibitors , Receptors, Notch/metabolism , Transcription Factor HES-1ABSTRACT
Laboratory experiments were conducted to study the molluscicidal activities of slow-release hexabutyldistannoxane (TBTO) and copper sulfate under various environmental conditions. Organic materials such as mud and weeds reduced the molluscicidal efficacy of both chemicals. TBTO can be considered a good long-lasting molluscicide but, because of uncertainty as to its general toxic effects, it should not be used in field trials. The molluscicidal activity of slow-release copper sulfate was short-lived in plain lake water and was nil in the presence of mud or weeds at the concentration used.
Subject(s)
Copper , Molluscacides , Trialkyltin Compounds , Environment , SulfatesABSTRACT
Urinary schistosomiasis is highly prevalent along the shores of the Volta Lake in Ghana, where transmission occurs focally in man-water contact sites. The intermediate host, Bulinus truncatus rohlfsi, prefers to harbour in Ceratophyllum, a common aquatic weed in the lake. Removal of this weed reduced the density of both infected and uninfected snails, but not sufficiently to interrupt transmission.Niclosamide was applied at 1, 0.7, and 0.5 mg/l in combination with weed removal at five water contact sites in December, January, and February, respectively. Plastic sheets were used to isolate treated sites from the main body of the lake. Snail surveys were carried out at short intervals to assess the effectiveness of these intervention measures. Niclosamide at 0.5 mg/l applied after weed removal was effective in killing the snails. The overall results indicate that snail control along the entire lake shore is impossible but that focal control of cercarial transmission at water contact sites is attainable and shows promise.
Subject(s)
Bulinus , Molluscacides , Niclosamide , Schistosomiasis/prevention & control , Animals , Ghana , Humans , Schistosoma haematobium , Schistosomiasis/transmissionABSTRACT
Snail surveys were carried out in Kpong Lake, in southern Ghana, and along the lower Volta River below the lake. Bulinus globosus and Biomphalaria pfeifferi were abundant in the Kpong Lake and B. truncatus and Biom . pfeifferi, especially the latter, were widespread below the lake. Urine surveys among primary school children at eight localities along the lower Volta showed Schistosoma haematobium prevalence rates of 38.8-96.2%. At Bator and Mepe , where records for an earlier survey were available for comparison, the present survey showed more than a doubling in prevalence rate in ten years: at Bator , from 27.1% in 1971-72 to 74.6% in 1981; at Mepe the corresponding figures were 36.4 and 88.0%. In Ghana infection with S. mansoni is less common than with S. haematobium and the known foci of S. mansoni transmission are few and widely scattered. In the present survey the disease is first reported along the lower Volta at Bator , Mepe , Adidome and Tefle , with prevalence rates ranging from 6.7% at Bator to 52.4% at Tefle . This survey has added an important focus of S. mansoni infection to those already known.
Subject(s)
Schistosomiasis/epidemiology , Adolescent , Animals , Biomphalaria/physiology , Bulinus/physiology , Child , Demography , Ghana , Humans , Schistosoma haematobium , Schistosoma mansoni , Schistosomiasis/transmissionABSTRACT
Bulinus truncatus rohlfsi is the intermediate host of urinary schistosomiasis, which is highly endemic in the man-made Volta Lake. In 1971, a WHO/UNDP schistosomiasis project was established in the Pawmpawm branch and part of the Afram branch of Volta Lake. Malacological findings of the preliminary phase indicated that the snails were distributed in the littoral zone of the lake, and that this distribution was correlated with the presence of vegetation, especially Ceratophyllum. Transmission nearly always occurred in "water contact sites", i.e., places where people come into contact with water.A snail-sampling technique with palm-leaf mats was developed and standardized after it had been shown in sensitivity trials to compare favourably with a modified version of the "man-time" sampling method, in which the number of snails collected per man-hour is recorded. It is recommended that both these methods should be used to conduct ecological studies of B. rohlfsi in water contact sites.
Subject(s)
Bulinus , Animals , Ecology , Fresh Water , Ghana , Population DensityABSTRACT
In the present ecological study of cercarial transmission of Schistosoma haematobium in the Volta Lake, Ghana, habitat observations and sampling of Bulinus truncatus rohlfsi were conducted within a 60-km stretch of shoreline. Observations revealed that human water contact sites in each village undergo constant changes in shape and vegetation. Snail sampling surveys in water contact sites were carried out monthly (for 27 months) in 8 villages using newly designed palm-leaf traps, and in 8 additional villages (for 16 months) using a modification of Olivier & Sneidermann's man-time method. Results to date confirm the finding by Chu & Vanderburg that cercarial transmission in the lake takes place almost exclusively within water contact sites. Additional results indicate that even within individual water contact sites this transmission is focal, most infected snails being found very close to the shoreline. Transmission also varies significantly according to shape, vegetation, and geographical location of the water contact sites, and is distinctly seasonal in most villages. These findings lead us to conclude that control of cercarial transmission in the Volta Lake is both attainable and feasible with existing methods.
Subject(s)
Bulinus/parasitology , Ecology , Schistosoma haematobium , Animals , Bulinus/isolation & purification , Climate , Disease Vectors/isolation & purification , Fresh Water , Geography , Ghana , Humans , Schistosomiasis/prevention & control , Schistosomiasis/transmission , Water MovementsABSTRACT
The present paper deals with longitudinal and cross-sectional methods of counting cercariae shed from Biomphalaria alexandrina in Egypt, both experimentally and naturally infected with schistosomes. By the longitudinal method, the daily output of cercariae was counted from the first shedding from experimentally infected snails and from the day of collection from naturally infected ones. The results show that the size of the snails at the time of shedding exerts a very large effect on the output of cercariae and that the numbers obtained in the laboratory are not representative of cercarial output in the field. By the cross-sectional method, the cercarial output in the first 24 hours from infected snails collected in different months from the field was counted. The results show that output is size-specific. When the size-specific output is adjusted to the size-composition of infected snails taken from the field, it is estimated that the daily output from infected snails in the field may be 957.7 cercariae. However, this number may vary with the season.