Differential Response of Pelvic Bone Marrow Fluorodeoxyglucose Uptake in Patients Receiving Concurrent Chemoradiotherapy.

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.

UK reporting radiographers' perceptions of AI in radiographic image interpretation - Current perspectives and future developments.

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 Qualtrics® 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 (n = 53, 62%). Less than a third of respondents would be confident communicating the AI decision to stakeholders. Affirmation from AI would improve confidence (n = 49, 57%) and disagreement would make respondents seek a second opinion (n = 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.

Artificial Intelligence: Guidance for clinical imaging and therapeutic radiography professionals, a summary by the Society of Radiographers AI working group.

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.

Oral health status of newly admitted residents living in residential aged care.

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.

A Prospective Study of Diffusion-weighted Magnetic Resonance Imaging as an Early Prognostic Biomarker in Chemoradiotherapy in Squamous Cell Carcinomas of the Anus.

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.

Is There a Role for an 18F-fluorodeoxyglucose-derived Biological Boost in Squamous Cell Anal Cancer?

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 threshold > 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.

Skin collagen can be accurately quantified through noninvasive optical method: Validation on a swine study.

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.

Comparison of four target volume definitions for pancreatic cancer. Guidelines for treatment of the lymphatics and the primary tumor.

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 11 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.

Ubiquitin C-terminal hydrolase L1 is required for pancreatic beta cell survival and function in lipotoxic conditions.

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.

Musashi expression in ß-cells coordinates insulin expression, apoptosis and proliferation in response to endoplasmic reticulum stress in diabetes.

Diabetes is associated with the death and dysfunction of insulin-producing pancreatic ß-cells. In other systems, Musashi genes regulate cell fate via Notch signaling, which we recently showed regulates ß-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 ß-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 ß-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 ß-cell proliferation. Our data also suggest that Musashi is a novel link between ER stress and the compensatory ß-cell proliferation and the loss of ß-cell gene expression seen in specific phases of the progression to type 2 diabetes.

Significance of genomic DNA group delineation in comparative studies of antimicrobial susceptibility of Acinetobacter spp.

There were significant differences in antimicrobial susceptibilities in isolates of genomic DNA groups 2 (Acinetobacter baumannii), 3, and 13TU collected from the same sources, e.g., patients in intensive care units and general wards, and in isolates of the same group collected from different sources. The delineation of genomic groups is important in comparative surveillance studies of antimicrobial susceptibilities.

Hantavirus-specific antibodies in rodents and humans living in Kuwait.

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.

Molecular, cellular and functional characterizations of a novel ICAM-like molecule of the immunoglobulin superfamily from Leishmania mexicana amazonensis.

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.

Epidemiology and infection control implications of Acinetobacter spp. in Hong Kong.

In a previous study, we showed that Acinetobacter genomic DNA group 3 was the most common species among blood culture isolates and was commonly found on superficial carriage sites of the healthy and the sick, which are different findings from those reported in Europe and North America. We used amplified ribosomal DNA restriction analysis and pulsed-field gel electrophoresis to study further the molecular epidemiology of acinetobacters in our region. Over a study period of 6 weeks with 136 consecutive routine clinical isolates (1.33% of all specimens), genomic DNA groups 2 (Acinetobacter baumannii), 3, and 13TU were obtained from 59 of 69 positive patients. There is a significant difference in the specimen sources of the three genomic DNA groups, with group 13TU being significantly associated with the respiratory tract (chi-square exact test, P = 0.0064). Settle plates showed a significantly heavier environmental load from the intensive care unit (ICU) than from the four surgical wards examined (22 of 70 versus 76 of 120 plates with <5 colonies; chi-square test, P < 0. 0001). Genomic group 3 accounted for 6 of 12 clusters of possibly related strains among patients, between patients and the ICU environment, and in the ICU environment. Genomic groups 2 and 3 accounted for 21% of the 132 genomically identified isolates recovered from 21 of 41 local vegetables, 53 of 74 fish and meat samples, and 22 of 60 soil samples. Group 13TU was present only in patients' immediate surroundings. The role played by the environment and by human carriage should be evaluated in order to devise a cost-effective infection control program pertinent to our situation of acinetobacter endemicity.

Colocalization of prostacyclin synthase with prostaglandin H synthase-1 (PGHS-1) but not phorbol ester-induced PGHS-2 in cultured endothelial cells.

The subcellular colocalization of prostacyclin synthase (PGIS) with prostaglandin H synthase (PGHS) has not been delineated. To test the hypothesis that its colocalization with PGHS is crucial for prostacyclin synthesis, we determined subcellular locations of PGIS, PGHS-1, and PGHS-2 in bovine aortic endothelial cells by immunofluorescent confocal microscopy. PGIS and PGHS-1 were colocalized to nuclear envelope (NE) and endoplasmic reticulum (ER) in resting and adenovirus-infected bovine aortic endothelial cells. PGIS and PGHS-2 were also colocalized to ER in serum-treated or adenovirus-cyclooxygenase-2-infected cells. By contrast, PGIS was not colocalized with PGHS-2 in cells induced with phorbol 12-myristate 13-acetate where PGHS-2 was visualized primarily in vesicle-like structures. The lack of colocalization was accompanied by failed prostacyclin production. Resting ECV304 cells did not produce prostacyclin and had no detectable PGHS-1 and PGIS proteins. Confocal analysis showed abnormal colocalization of PGIS and PGHS-1 to a filamentous structure. Interestingly, the abundant PGIS and PGHS-1 expressed in adenovirus-infected ECV304 cells were colocalized to NE and ER, which synthesized a large quantity of prostacyclin. These findings underscore the importance of colocalization of PGHS and PGIS to ER and NE in prostacyclin synthesis.

Effects of chronic stress on food acquisition, plasma hormones, and the estrous cycle of female rats.

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.

Arachidonic acid stimulates the intrinsic activity of ubiquitous glucose transporter (GLUT1) in 3T3-L1 adipocytes by a protein kinase C-independent mechanism.

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.

Enfermedades parasitarias y desarrollo hidraúlico: necesidad de una negociación intersectorial / Enfermedades parasitarias y desarrollo hidraúlico: necesidad de una negociación intersectorial / Parasitic diseases in water resources development : The need for intersectoral negociation

La explotación de los recursos hídricos es un requisito esencial para una amplia gama de actividades humanas, en particular la agricultura y la producción de energía. Sin embargo, hoy se conocen cada vez mjeor los posibles efectos negativos de ese aspecto del desarrollo, entre los que destacan el aumento de la prevalencia de ciertas parasitosis en la población de las zonas vecinas. No obstante, apenas se han tomado medidas eficaces para contrarrestar esos efectos de los proyectos hidr—licos, tanto en la fase de planificación como al aparecer los primeros signos alarmantes, y de hecho el sector sanitario tiende a estar mal preparado para hacer frente a estos problemas

En el presente volumen se examinan los efectos de los proyectos de explotación de recursos hídricos en cuatro enfermedades parasitarias: la esquistosomiases, el paludismo, la filariasis linfática y la oncocercosis, todas las cuales pueden prevenirse o combatirse actualmente con los conocimientos disponibles. A continuación se exponen algunas posibles medidas para proteger a la población en los proyectos de ese tipo, indicando las estrategias de negociación intersectorial que pueden aplicar los funcionarios de sanidad y las modalidades de preparación de un plan sanitario para un proyecto hidr—lico. A lo largo

Parasitoses et mise en valeur des ressources hydriques : un impératif, la négociation intersectorielle / J. M. Hunter ... [et al.] / Parasitic diseases in water resources development : the need for intersectoral negotiation

Cet ouvrage lance un appel à l'action pour que soient prises en considération les conséquences sur la santé des grands projets d'irrigation ou de barrages, trop souvent négligées jusqu'à présent. Il expose un certain nombre d'arguments et de lignes de conduite visant à atténuer les souffrances humaines et les problèmes qui se posent lorsque des projets d'aménagement hydrulique sont exécutés sans que des mesures parallèles de lutte contre la maladie ne soient prévues. Considérant les maladies parasitaires comme l'indicateur le plus fiable et le plus spectaculaire des effets défavorables sur la santé, il a pour but de persuader les personnes qui financent, planifient et gèrent ces projets de placer les préoccupations sanitaires au centre du dialogue sur le développement. A cette fin, il s'appuie sur une masse d'éléments tendant à montrer à la fois l'ampleur des risques pour la santé liés à ce type de projets et la faisabilité des mesures de prévention et de lutte. Mettant en cause le rôle traditionnellement passif du secteur de la santé, il vise également à inciter les autorités sanitaires à prendre part au processus d'élaboration des projets et à faire davantage entendre leur voix. Cet ouvrage comporte neuf chapitres. Le premier donne une vue d'ensemble du problème, en insistant sur les raisons pour lesquelles l'impact des politiques de développement sur la santé n'est toujours pas pris en compte bien qu'il ait été largement démontré. Le deuxième chapitre explique comment les projets d'aména-gement hydraulique peuvent aggraver les parasitoses et analyse l'importance des boule-versements qu'ils entraînent dans le cadre plus large des politiques de développement et de leurs objectifs. Une attention particulière a été accordée à l'impact des nouvelles conditions écologiques sur l'introduction, la propagation ou l'aggravation du paludisme, de la schistosomiase et de la filariose lymphatique. Le troisième chapitre passe en revue de façon détaillée les éléments qui permettent de lier certains aspects des projets de développement aux modifications de l'incidence et de la prévalence de ces maladies. S'appuyant sur des données provenant d'études réalisées sur plus de 60 barrages ou réseaux d'irrigation, les auteurs mettent en évidence, cas par cas, l'aggravation des risques pour la santé du fait de la transformation des écosystèmes. Si l'on trouve quelques cas de projets bien planifiés, les projets font, dans l'ensemble, complètement abstraction des risques à court ou à long terme pour la santé. Le cas particulier des petits barrages est abordé au quatrième chapitre. Après avoir démontré qu'il était urgent d'apporter des changements au niveau des politiques, la deuxième moitié de l'ouvrage propose des lignes de conduite. Un bilan des mesures techniques de lutte contre le paludisme, la schistosomiase et la filariose lymphatique montre que les maladies parasitaires sont un risque évitable dans le cadre des projets d'aménagement hydraulique. Les chapitres suivants passent en revue les raisons pour lesquelles ces techniques très efficaces ne sont pas appliquées et décrivent différents moyens d'infléchir les politiques. C'est ainsi qu'il est proposé d'utiliser une part du revenu brut du projet pour financer les coûts de protection de la santé à travers l'élaboration de réglementations nationales régissant l'exploi-tation à long terme d'un projet, ou bien encore d'avoir recours à "l'endettement en vue de la santé" pour garantir le soutien financier. Enfin, les derniers chapitres, qui s'adressent aux autorités sanitaires, contiennent des conseils pratiques sur la façon de négocier avec les autres secteurs et d'établir un plan d'action sanitaire valable pour un projet d'aménagement hydraulique. Ils contiennent une série de six arguments clés qui peuvent constituer la base d'une stratégie de négociation persuasive

Enfermedades parasitarias y desarrollo hidr'aulico : necesidad de una negociaci'on intersectorial / J. M. Hunter ... [et al.] / Parasitic diseases in water resources development : the need for intersectoral negotiation

Este libro es un llamamiento para que se corrija el grave error consistente en descuidar las consecuencias sanitarias de los proyectos de embalse de aguas y de riego. Los argumentos aducidos y las líneas de acción propuestas responden a la magnitud verificada del sufri-miento y de la incapacitación que acarrean los proyectos de desarrollo de recursos hídricos si no prevén la lucha contra las enfermedades. Concentrándose en las enfermedades parasita-rias como los indicadores más visibles y fiables de los efectos nocivos para la salud, el libro se propone persuadir a los responsables de la financiación, a los planificadores y a los admi-nistradores de esos proyectos para que hagan de la preocupación por la salud un elemento central del diálogo sobre el desarrollo. Con esa finalidad, el libro se apoya en una gran cantidad de pruebas para demostrar tanto la magnitud de los riesgos sanitarios que llevan aparejados los proyectos como la posibilidad de prevenir y limitar esos riesgos. Mencionando el papel tradi-cionalmente pasivo del sector sanitario como factor contribuyente, el libro también tiene por objeto alentar a las autoridades sanitarias a intervenir en el ciclo de los proyectos con una voz más insistente. Todo a lo largo del libro se presta especial atención a los conocimientos recientes acerca de las enfermedades parasitarias, los cuales demuestran que es posible formular políticas que hagan compatible el objetivo de progreso económico con la protección y la promoción de la salud. El libro consta de nueve capítulos. En el primero se presenta una panorámica del problema, con-centrándose en las razones por las cuales las repercusiones sanitarias de las políticas de desarrollo se siguen desatendiendo pese a las pruebas abrumadoras de las consecuencias de esa actitud. Los autores también explican por qué ha sonado la hora de fijarse en las repercusiones sanitarias y ecológicas de esas políticas. En el segundo capítulo se explican las numerosas formas en que los proyectos de desarrollo hídrico pueden favorecer las enfer-medades parasitarias y se examina la impor-tancia de ello en el contexto más amplio de las políticas de desarrollo y de los objetivos de éstas. Se presta especial atención a las reper-cusiones de las nuevas condiciones ecológicas en la aparición, la propagación y el agrava-miento del paludismo, de la esquistosomiasis y de la filariasis linfática. El tercer capítulo contiene un examen detallado de las pruebas de la relación existente entre determinadas características de los proyectos y la modifica-ción de la incidencia y la prevalencia de esas enfermedades. Basándose en los resultados del estudio de más de 60 presas y sistemas de riego, los autores presentan, caso por caso, las pruebas del agravamiento de los riesgos sanitarios resultantes de la transformación de los ecosistemas. Se describen algunos proyectos bien planificados, pero el panorama generales de una desatención sistemática de los peligros sanitarios amenazantes tanto en el corto como en el largo plazo. El cuarto capítulo versa sobre el caso especial de las pequeñas presas. Tras haber demostrado la necesidad urgente de modificar las políticas, la segunda mitad del libro traza líneas de acción. Un examen de las medidas técnicas para combatir el paludismo, la esquistosomiasis y la filariasis linfática mues-tra que las enfermedades parasitarias son un riesgo evitable de los planes de fomento de recursos hídricos. En los capítulos siguientes se examinan las razones por las cuales esas eficaces técnicas no se han llevado a la práctica y se describen diferentes métodos para lograr que se modifiquen las políticas. Las propuestas van desde la utilización de una parte de los ingresos brutos generados por el proyecto para solventar los costos del mantenimiento de la salud, pasando por el establecimiento de una reglamentación nacional que rija el funciona-miento a largo plazo de un proyecto, hasta el establecimiento de un ±intercambio de deuda por bi