Protecting environmental flows to achieve long-term water security.

In this work, we propose a new approach to diagnose if a water allocation scheme is compatible with long-term water security at the catchment scale, and suggest steps to achieve such compatibility. We argue that when the remaining flow of a river after upstream withdrawals is not sufficient to safeguarding ecological river functions, the basin is at extreme risk of water scarcity, which indicates that the water management is failing. To test this, we analysed the water scarcity risks and the safeguarded environmental flows (e-flows) in 277 basins across a wide range of hydro-climatic conditions in Chile (17-55°S). For each basin, water scarcity risks were assessed based on water stress indices (WSIs, computed as the ratio of withdrawals to water availability), considering two water-use scenarios: (i) WSImax, where total withdrawals correspond to the maximum consumptive water allowed by the law, i.e., where only the e-flows protected by law remain in the river, and (ii) WSIalloc, where total withdrawals correspond to the actual allocated consumptive water uses within the basins. Further, we evaluated the adequacy of the water management system to protect ecological river functions by contrasting the e-flows protected in Chile with those safeguarded in six other countries. The water allocation system in Chile incorporated the protection of minimum e-flows in 2005 and established that these do not exceed 20% of the mean annual streamflow, except in some exceptional cases. This upper limit is consistently lower than the e-flows safeguarded in other countries, where 20%-80% of the mean annual streamflow are protected. This turns out in WSImax values between 80% and 100% in all basins, well above the threshold associated with over-committed basins under extreme risk of water scarcity (70% typically). When moving from the legally allowed to the actually allocated water use scenario, we found contrasting results: about 70% of the basins show low water scarcity risk (WSIalloc <40%), while an 18% have WSIalloc above 100%, indicating the allocation is going beyond current law limits and even beyond physical limits. Our results reveal that the link between e-flows, water allocation and water security has not been adequately incorporated in the current law. E-flows stipulated by law are insufficient to fulfil environmental requirements, while placing the basins under extreme risk of water scarcity if the total allowed withdrawals were exerted. To move towards a system that can effectively achieve long-term water security, we recommend: (i) To define tolerable water scarcity risks for basins, considering environmental requirements. (ii) To translate those risks into measurable basin indices to measure water security, such as the WSI. (iii) To set maximum water use limits (or minimum e-flows) within the basins that are compatible to the water security goals. If, under current and projected water availability conditions, the existing withdrawals exceed these limits, water managers should be able to adapt total consumption to the required limits.

Transcriptional fine-tuning of microRNA-223 levels directs lineage choice of human hematopoietic progenitors.

MicroRNAs (miRNAs) regulate cell proliferation, differentiation and death during development and postnatal life. The expression level of mature miRNAs results from complex molecular mechanisms, including the transcriptional regulation of their genes. MiR-223 is a hematopoietic-specific miRNA participating in regulatory signaling networks involving lineage-specific transcription factors (TFs). However, the transcriptional mechanisms governing its expression levels and its functional role in lineage fate decision of human hematopoietic progenitors (HPCs) have not yet been clarified. We found that in CD34(+)HPCs undergoing unilineage differentiation/maturation, miR-223 is upregulated more than 10-fold during granulopoiesis, 3-fold during monocytopoiesis and maintained at low levels during erythropoiesis. Chromatin immunoprecipitation and promoter luciferase assays showed that the lineage-specific expression level of mature miR-223 is controlled by the coordinated binding of TFs to their DNA-responsive elements located in 'distal' and 'proximal' regulatory regions of the miR-223 gene, differentially regulating the transcription of two primary transcripts (pri-miRs). All this drives myeloid progenitor maturation into specific lineages. Accordingly, modulation of miR-223 activity in CD34(+)HPCs and myeloid cell lines significantly affects their differentiation/maturation into erythroid, granulocytic and monocytic/macrophagic lineages. MiR-223 overexpression increases granulopoiesis and impairs erythroid and monocytic/macrophagic differentiation. Its knockdown, meanwhile, impairs granulopoiesis and facilitates erythropoiesis and monocytic/macrophagic differentiation. Overall, our data reveal that transcriptional pathways acting on the differential regulation of two pri-miR transcripts results in the fine-tuning of a single mature miRNA expression level, which dictates the lineage fate decision of hematopoietic myeloid progenitors.

The impact of a multidisciplinary approach on response rate of mandibular advancing device therapy in patients with obstructive sleep apnoea syndrome.

The aim of the present study was to evaluate the importance of a multidisciplinary approach on increasing the response ratio expectation to mandibular advancing device (MAD) therapy in patients with obstructive sleep apnoea syndrome, especially in severe cases. Forty-two mild-to-severe OSAS patients were selected, after comprehensive evaluation by neurologists, otorhinolaryngologists and orthodontists, and treated with a Somnodent® device. Six months later, a polysomnographic exam with the MAD in situ was performed. The paired t-test evaluated the effectiveness of therapy and the results were compared with data from systematic reviews. The average treatment response was statistically significant for the apnoea/hypopnea index (AHI) and oxygen desaturation index and was higher than the outcomes presented in literature. An optimum therapy response (AHI < 5) was observed in 53% of patients (40% in severe OSAS) and a good response (AHI < 10) in 73% of patients (50% in severe OSAS). The Somnodent® device was effective and the multidisciplinary patient selection improved the response ratio compared to that reported by previous systematic reviews.

Evaluation of an in-clinic assay for the diagnosis of canine parvovirus.

The results of a study designed to evaluate the performance of an in-clinic test for the detection of canine parvovirus (CPV) are reported. A total of 150 faecal samples collected from dogs with acute diarrhoea were tested using the in-clinic test, a haemagglutination assay (HA) and a real-time PCR assay for CPV detection, quantification and characterisation. CPV was detected in 66, 73, and 101 faecal samples by in-clinic, HA and PCR testing, respectively. The relative sensitivity and specificity of the in-clinic test were 86.3% and 96.1%, respectively, when the test was compared to HA, and 65.3% and 100%, respectively, when compared to real-time PCR. The sample distribution according to the virus type was CPV-2a, n=44; CPV-2b, n=11; CPV-2c, n=44, CPV-2, n=2, as determined by minor groove binder probe assays and/or sequence analysis. The percentage of positive in-clinic tests was 70.5% for CPV-2a, 72.7% for CPV-2b and 75.0% for CPV-2c (P>0.05). Using real-time PCR as the reference standard for CPV detection, the in-clinic test was more specific than HA and had comparable sensitivity to HA, demonstrating detection rates similar to those previously observed for other rapid in-clinic tests. The in-clinic test was also able to detect all CPV types at equivalent rates.

[Mandibular atrophy and a screw-retained implant-supported prosthesis]. / Atrophie mandibulaire et prothèse implantoportée, fixe, vissée. Etude préliminaire de 7 cas.

Prosthetic care for mandibular atrophy has raised many difficult problems, particularly in the most severe cases. The solution to most of these problems lies in the use of osteointegrated implants. Good results were obtained by using a small number of implants associated with adjustable overdenture prostheses or, alternatively, by using a larger number of implants (5 or 6) associated with a screw fixed prosthesis with posterior cantilever. Cantilever prostheses can provide support for the mental foramen zones and the posterior zones of the mandibular body where bone resorption is important after application of adjustable plates to the fibromucosa.

Behavior of circulating endothelin-1 in a group of patients with acute myocardial infarction.

The aim of this study was to investigate the behavior of plasma endothelin-1 (ET-1) in 23 patients with acute myocardial infarction, complicated and uncomplicated by left ventricular failure, and treated with and without thrombolytic agents. ET-1 was measured on admission; on days 2, 3, and 5; and again on discharge. In addition, on discharge, ET-1 was correlated with left ventricular systolic function. Left ventricular failure was present, on admission, in 14 patients, whereas the other nine did not have any hemodynamic impairment. On discharge, no patients had left ventricular failure, but 11 had moderate to severe left ventricular systolic dysfunction, defined as left ventricular ejection fraction (LVEF) < 40%. Fourteen subjects, matched for age and sex, served as a control group. Compared with the control range, ET-1 was highly elevated on the first day, in both uncomplicated (p < 0.01) and complicated patients (p < 0.001). Then it decreased rapidly in the uncomplicated group, reaching the control range within day 5, whereas in the complicated group it remained significantly elevated in comparison with both the control subjects and the uncomplicated patients, until discharge. ET-1 was not correlated with the peak of creatine-kinase MB isoenzyme in any group. In seven patients submitted to thrombolytic treatment ET-1 was always significantly lower than in the nonthrombolyzed patients (p < 0.05), but the pattern of variation across time was no different. On discharge, the difference in plasma ET-1 between patients with LVEF < 40% and the control group was significant (p < 0.001), as was the difference between patients with and without moderate to severe systolic dysfunction (p < 0.01). ET-1 was closely and inversely correlated with LVEF when patients were considered as a whole (p < 0.001). These results suggest that the ET-1 increase in the early phase of myocardial infarction could be due to an ischemic process, to stress reaction, and to cardiac hemodynamic impairment, and therefore, ET-1 may be a good marker of disease. In the following phase the ET-1, being correlated with LVEF, could be a reliable index of systolic function.

ALK expression defines a distinct group of T/null lymphomas ("ALK lymphomas") with a wide morphological spectrum.

The t(2;5)(p23;q35) translocation associated with CD30-positive anaplastic large cell lymphoma results in the production of a NPM-ALK chimeric protein, consisting of the N-terminal portion of the NPM protein joined to the entire cytoplasmic domain of the neural receptor tyrosine kinase ALK. The ALK gene products were identified in paraffm sections by using a new anti-ALK (cytoplasmic portion) monoclonal antibody (ALKc) that tends to react more strongly than a previously described ALK1 antibody with the nuclei of ALK-expressing tumor cells after microwave heating in 1 mmol/L ethylenediaminetetraacetic acid buffer, pH 8.0. The ALKc monoclonal antibody reacted selectively with 60% of anaplastic large cell lymphoma cases (60 of 100), which occurred mainly in the first three decades of life and consistently displayed a T/null phenotype. This group of ALK-positive tumors showed a wide morphological spectrum including cases with features of anaplastic large cell lymphoma "common" type (75%), "lymphohistiocytic" (10%), "small cell" (8.3%), "giant cell" (3.3%), and "Hodgkin's like" (3.3%). CD30-positive large anaplastic cells expressing the ALK protein both in the cytoplasm and nucleus represented the dominant tumor population in the common, Hodgkin's-like and giant cell types, but they were present at a smaller percentage (often with a perivascular distribution) also in cases with lymphohistiocytic and small cell features. In this study, the ALKc antibody also allowed us to identify small neoplastic cells (usually CD30 negative) with nucleus-restricted ALK positivity that were, by definition, more evident in the small cell variant but were also found in cases with lymphohistiocytic, common, and "Hodgkin's-like" features. These findings, which have not been previously emphasized, strongly suggest that the neoplastic lesion (the NPM-ALK gene) must be present both in the large anaplastic and small tumor cells, and that ALK-positive lymphomas lie on a spectrum, their position being defined by the ratio of small to large neoplastic cells. Notably, about 15% of all ALK-positive lymphomas (usually of the common or giant cell variant) showed a cytoplasm-restricted ALK positivity, which suggests that the ALK gene may have fused with a partner(s) other than NPM. From a diagnostic point of view, detection of the ALK protein was useful in distinguishing anaplastic large cell lymphoma cases of lymphohistiocytic and small cell variants from reactive conditions and other peripheral T-cell lymphoma subtypes, as well as for detecting a small number of tumor cells in lymphohemopoietic tissues. In conclusion, ALK positivity appears to define a clinicopathological entity with a T/null phenotype ("ALK lymphomas"), but one that shows a wider spectrum of morphological patterns than has been appreciated in the past.

Atrial natriuretic peptide and acute myocardial infarction: critical reappraisal.

The present investigation was designed to assess the correlation of atrial natriuretic peptide (ANP) with the ordinary markers of acute myocardial infarction (AMI). In 15 patients with uncomplicated AMI, no remarkable variation in ANP plasma levels was found. On the other hand, serum myoglobin and cardiac enzymes behaved as usual. Our results show that ANP is not correlated with serum myoglobin, creatine-phosphokinase and its isoenzyme MB, being completely independent from these markers of myocardial injury. These observations suggest that the plasma ANP variations observed in AMI by other investigators are probably dependent on hemodynamic dysfunction.

[Development of the sympatoadrenergic function in the fetus and the newborn infant]. / Sviluppo della funzione simpatoadrenergica nel feto e nel neonato.

An analysis of the available data concerning the events bringing to the completion of the adrenergic function in early life shows the existence of an early response making the detection of MOPEG-SO4 levels in the urine--the foetus and in the new-born. This response isn't the same in the adult and in the infant as in the latter the number of receptors is lower, the prevalent mediator is NA and the receptorial subtype is almost entirely beta. The effector system, on the contrary, is as fully developed in the infant as it's in the adult. Maybe it will be possible in the future to evaluate--through non-invasive methods such as the detection of MOPEG-SO4 levels in the urine--the degree of development of the central simpatoadrenergic system in order to exactly work out perinatal asphyxia and brains congenital injuries.