Determination of environmental flows in rivers using an integrated hydrological-hydrodynamic-habitat modelling approach.

We propose the novel integrated modelling procedure 3H-EMC for the determination of the environmental flow in rivers and streams; 3H-EMC combines Hydrological, Hydrodynamic and Habitat modelling with the use of the Environmental Management Classes (EMCs) that are defined by the Global Environmental Flow Calculator. We apply 3H-EMC in the Sperchios River in Central Greece, in which water abstractions for irrigation cause significant environmental impacts. Calculations of the hydrodynamic-habitat model, in which the large and the small chub are the main fish species, suggest discharge values that range from 1.0 m3/s to 4.0 m3/s. However, hydrological modelling indicates that it is practically difficult to achieve discharges that are higher than approximately 1.0-1.5 m3/s. Furthermore, legislation suggests significantly lower values (0.4-0.5 m3/s) that are unacceptable from the ecological point of view. This behaviour shows that a non-integrated approach, which is based only on hydrodynamic-habitat modelling does not necessarily result in realistic environmental flows, and thus an integrated approach is required. We propose the value of 1.0 m3/s as the "optimum" environmental flow for Sperchios River, because (a) it satisfies the habitat requirements, as expressed by the values of weighted useable area that are equal to 2180 and 1964 m2 for the large and small chub, respectively, and correspond to 82 and 95% of their respective maximum values, (b) it is consistent with the requirements of Environmental Classes A and B, whose percentiles are higher than 75% for discharge (77.2%) and for habitat availability (>83.5% for the large chub and >85.0% for the small chub), (c) it is practically achievable from the hydrological point of view, and (d) it is higher than the value proposed by the Greek legislation. The proposed modelling approach can be applied to any river or stream using the same or similar modelling tools, which should be linked via suitable coupling algorithms.

Neuroradiological, neurophysiological and molecular findings in infantile Krabbe disease: two case reports.

Krabbe disease is an autosomal recessive neurodegenerative disorder due to a defect of the lysosomal enzyme ß-galactocerebrosidase (ß-GALC). Depending on the age of onset, the disease is classified into infantile and later-onset forms. We report neuroradiological, neurophysiological and molecular findings in two Greek patients with the infantile form of Krabbe disease. The index patients presented at the age of 3.5 and 6 months, respectively, due to developmental delay. Magnetic resonance imaging (MRI) of the first patient's brain demonstrated signs of leukodystrophy, while nerve conduction velocities (NCVs) were significantly decreased. The second patient's MRI at the age of 4 months was initially normal, but at 18 months demonstrated leukodystrophic alterations as well, whereas NCVs were also significantly delayed. In both patients, a severe decrease in ß-GALC, activity supported the diagnosis of Krabbe disease, while the final diagnosis was confirmed by molecular genetic testing. Two homozygous mutations of the GALC gene, the c.411_413delTAA [p.K139del] mutation in the first patient, and the c.749T>C [p.I250T] mutation in the second patient, were identified. At their last follow-up visit at the age of 4 and 6 years, respectively, both patients were bedridden and quadri-plegic, suffering from frequent respiratory tract infections and fed through a gastrostomy. Both mutations found in homozygosity in these two unrelated patients of Greek ancestry, could pinpoint a common origin. Genotyping of patients with Krabbe disease is important, in order to contribute to the creation of a European mutation database and to further study possible genotype-phenotype correlations of the disease.

Niemann-Pick type C disease: a novel NPC1 mutation segregating in a Greek island.

Niemann-Pick type C (NPC) disease is a rare autosomal recessive lysosomal storage disease, exhibiting an extremely heterogeneous clinical phenotype. It is a cellular lipid trafficking disorder characterized by the accumulation in the lysosomal/late endosomal system of a variety of lipids, especially unesterified cholesterol. So far two genes, NPC1 or NPC2, have been linked to the disorder. It is a panethnic disease for which two isolates have been described. We present a novel NPC1 mutation (p.A1132P; c.3394G>C) identified in homozygosity in two patients originating from the same small town of an Aegean Sea island and the results of the broad screening of their extended families. Overall 153 individuals have so far been investigated and a total of 64 carriers were identified. Moreover a common descent of the individuals tested was revealed and all carriers could be traced back to a common surname, apparently originating from a common ancestor couple six generations back. The mutation was found associated with an uncommon haplotype in the island that is also present in other populations.

Water quality monitoring and assessment of an urban Mediterranean lake facilitated by remote sensing applications.

Degradation of water quality is a major problem worldwide and often leads to serious environmental impacts and concerns about public health. In this study, the water quality monitoring and assessment of the Koumoundourou Lake, a brackish urban shallow lake located in the northeastern part of Elefsis Bay (Greece), were evaluated. A number of water quality parameters (pH, temperature, dissolved oxygen concentration, electrical conductivity, turbidity, nutrients, and chlorophyll-a concentration) were analyzed in water samples collected bimonthly over a 1-year period from five stations throughout the lake. Moreover, biological quality elements were analysed seasonally over the 1-year period (benthic fauna). Statistical analysis was performed in order to evaluate the water quality of the lake and distinguish sources of variation measured in the samples. Furthermore, the chemical and trophic status of the lake was evaluated according to the most widely applicable classification schemes. Satellite images of Landsat 5 Thematic Mapper were used in order for algorithms to be developed and calculate the concentration of chlorophyll-a (Chl-a). The trophic status of the lake was characterized as oligotrophic based on phosphorus and as mesotrophic-eutrophic based on Chl-a concentrations. The results of the remote sensing application indicated a relatively high coefficient of determination (R (2)) among point sampling results and the remotely sensed data, which implies that the selected algorithm is reliable and could be used for the monitoring of Chl-a concentration in the particular water body when no field data are available.

The thickness and volume of LLETZ specimens can predict the relative risk of pregnancy-related morbidity.

OBJECTIVE: The aim of this study was to determine if the individual physical characteristics of the extirpated transformation zone after large loop excision of the transformation zone (LLETZ) might predict the relative risk of adverse obstetric outcome, specifically preterm labour (PTL). DESIGN: A retrospective observational study. SETTING: University teaching hospital in Dublin (Coombe Women & Infants University Hospital, CWIUH). POPULATION: Women who had LLETZ treatment for cervical intraepithelial neoplasia (CIN) in the colposcopy service between 1999 and 2002, and who subsequently had a pregnancy at the CWIUH. METHODS: Case records and histology reports for eligible women were examined. Age, parity, smoking history, pregnancy complications and CIN grade were recorded. Exclusion criteria were age >42 years, previous treatment for CIN, previous premature labour or twin pregnancies. The Student's t-test, Mann-Whitney U-test, analysis of variants (ANOVA) and logistic regression were employed to analyse the data. MAIN OUTCOME MEASURES: Gestational age at birth, PTL (i.e. <37 weeks of gestation) and miscarriage rate (<24 weeks of gestation). RESULTS: Out of 1808 women who underwent LLETZ treatment, a total of 353 women were identified who subsequently had a pregnancy at the CWIUH, with 321 being eligible for inclusion in the study. Of these, 76.3% delivered at term, 9.1% delivered at <37 weeks of gestation and 14.6% miscarried at <24 weeks of gestation. There was a three-fold increase in the risk of PTL if the excision volume exceeded 6 cm(3) (RR = 3.00; 95% CI 1.45-5.92), or when the thickness of the excised tissue was greater than 12 mm (RR = 2.98; 95% CI 1.27-7.01). The time interval between LLETZ and pregnancy did not appear to have an effect on PTL rates. We found no association between the grade of CIN and the risk of PTL. CONCLUSIONS: This study reveals that the thickness and the total volume of the excised transformation zone are associated with an increased risk of PTL. Excisions thicker than 1.2 cm and larger than 6 cm(3) carry a three times greater risk for PTL.

Mitochondrial neurogastrointestinal encephalomyopathy: Clinical and biochemical impact of allogeneic stem cell transplantation in a Greek patient with one novel TYMP mutation.

We describe the case of a Greek female patient with the Classic form of the ultra- rare and fatal autosomal recessive disorder Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) and the impact of allogeneic hematopoietic stem cell transplantation on the biochemical and clinical aspects of the disease. The patient presented at the age of 15 years with severe gastrointestinal symptoms, cachexia, peripheral neuropathy and diffuse leukoencephalopathy. The diagnosis of MNGIE disease was established by the increased levels of thymidine and deoxyuridine in plasma and the complete deficiency of thymidine phosphorylase activity. The novel c.[978dup] (p.Ala327Argfs*?) variant and the previously described variant c.[417 + 1G > A] were identified in TYMP. The donor for the allogeneic hematopoietic stem cell transplantation was her fully compatible sister, a carrier of the disease. The patient had a completely uneventful post- transplant period and satisfactory PB chimerism levels. A marked and rapid decrease in thymidine and deoxyuridine plasma levels and an increase of the thymidine phosphorylase activity to the levels measured in her donor sister was observed and is still present sixteen months post-transplant. Disease symptoms stabilized and some improvement was also observed both in her neurological and gastrointestinal symptoms. Follow up studies will be essential for determining the long term impact of allogeneic hematopoietic stem cell transplantation in our patient.

Relaxin as a potential diagnostic biomarker for ovarian cancer- A prospective study.

Ovarian cancer is a leading cause of female mortality worldwide. Although novel approaches on this disease have been developed, overall survival rates remain moderate due to the lack of scientific evidence promoting screening at early stages of the disease. A number of biomarkers have been suggested as predictive for this type of cancer. The role of relaxin in endometrial cancer is well documented but the scientific evidence is lacking with regards to ovarian cancer. We studied patients with ovarian cancer, benign ovarian cyst and healthy patients too. The levels of relaxin have been found to be an adequate diagnostic biomarker for ovarian cancer. We also presented the different range of Ca125, HE4 and ROMA in these three groups. Randomised control trials need to be conducted though, in order to elucidate the true role of relaxin in these cases.

Chitotriosidase plasma activity in nephropathic cystinosis.

Chitotriosidase is a fully active chitinase produced and secreted by activated phagocytes. Plasma chitotriosidase activity is a well-established marker of total disease burden in Gaucher disease that has proved useful in monitoring the response to both enzyme replacement and substrate reduction therapies in patients with Gaucher disease. Increased chitotriosidase plasma activity has also been observed in several other lysosomal and non lysosomal disorders. Cystinosis, a rare multisystemic lysosomal storage disease, is characterized by the intralysosomal accumulation of free cystine in many cell types including phagocytes. We here report on plasma chitotriosidase activity in a child with nephropathic cystinosis. Increased plasma chitotriosidase activity (481 nmol/h per ml; normal range 0-150 units) was found on diagnosis and prior to the initiation of oral cysteamine (Cystagon) treatment. Serial estimations of plasma chitotriosidase activity showed that it correlated with leukocyte cystine content and decreased to 100 nmol/h per ml following 14 months' treatment. This novel observation suggests that cystinosis should be included in the differential diagnosis of disorders associated with increased plasma chitotriosidase activity. Furthermore, it suggests that serial estimations of plasma chitotriosidase activity could be of value in monitoring the response to oral cysteamine treatment in cystinosis.

Nitrogen loading and natural pressures on the water quality of a shallow Mediterranean lake.

The water quality of Koumoundourou Lake, a heavily modified, peri-urban, brackish and shallow lake near Athens, Greece, is under multiple stressors due to the industrial activities in the catchment area and natural pollution pressures. Although the broader area has undergone significant land use changes since the beginning of the 20th century converting it from rural to heavily industrialized, Koumoundourou Lake remained as one of the few habitats in Attica Region, for large numbers of aquatic birds. The water quality of the lake has been recently improved, which contributed to the increase of aquatic birds' population in the area and to the higher, in relation to the past, nitrogen inputs from natural sources. Therefore, a monitoring program has been implemented to assess the pollution pressure factors in the lake. A water quality model has been also used to simulate the lake's processes and estimate the nutrient mass budget focusing on the various nitrogen loading mechanisms (natural and anthropogenic). Based on the model output, the main polluting factor of the lake is the groundwater inflows. Aquatic birds affect slightly the lake's water quality, while the dry and wet atmospheric deposition contributes insignificantly to the total nitrogen loading.

Historical trends and the long-term changes of the hydrological cycle components in a Mediterranean river basin.

Identifying the historical hydrometeorological trends in a river basin is necessary for understanding the dominant interactions between climate, human activities and local hydromorphological conditions. Estimating the hydrological reference conditions in a river is also crucial for estimating accurately the impacts from human water related activities and design appropriate water management schemes. In this effort, the output of a regional past climate model was used, covering the period from 1660 to 1990, in combination with a dynamic, spatially distributed, hydrologic model to estimate the past and recent trends in the main hydrologic parameters such as overland flow, water storages and evapotranspiration, in a Mediterranean river basin. The simulated past hydrologic conditions (1660-1960) were compared with the current hydrologic regime (1960-1990), to assess the magnitude of human and natural impacts on the identified hydrologic trends. The hydrological components of the recent period of 2008-2016 were also examined in relation to the impact of human activities. The estimated long-term trends of the hydrologic parameters were partially assigned to varying atmospheric forcing due to volcanic activity combined with spontaneous meteorological fluctuations.

Serum S100B levels in X-linked adrenoleukodystrophy and Gaucher disease.

S100B, a small acidic protein, is a member of a multigenic family of calcium-modulated proteins. It is mainly produced by astrocytes and the secreted protein, depending on its concentration, can exert either trophic or toxic effects. In humans increased S100B levels have been detected in brain trauma and ischaemia, and neurodegenerative, neurometabolic, inflammatory and psychiatric disease. Serum S100B concentrations have been used as markers of brain disease. In the present study S100B serum levels were determined in patients with the neuroinflammatory disease X-linked adrenoleukodystrophy (X-ALD) and in patients with both the acute neuronopathic (type II) and the non-neuronopathic (type I) types of Gaucher disease (GD). Sixteen X-ALD patients (10 with the childhood, 4 with the adult cerebral forms, 2 asymptomatic) and 22 Gaucher disease patients (19 type I, 3 type II) were studied. No statistically significant differences were observed between the X-ALD (median 0.13 microg/L, p=0.191) or Gaucher type I patients (median 0.07 microg/L, p=0.095) and controls of similar age (median 0.10 microg/L, n=22). Serum S100B levels of type II Gaucher disease patients were also within the normal for their age range (patients 0.2, 0.22, 0.65; control median 0.81 microg/L, n=44). Lack of clinical symptoms and/or MRI findings in X-ALD patients was not associated with lower S100B values. Our results indicate that serum S100B levels cannot serve as peripheral marker in the evaluation of brain disease in X-ALD and GD.

Iron overload and kidney lysosomes.

Iron overload has been associated with damage of the liver and other organs of patients with primary or secondary increased iron load. In order to study the effect of iron overload on the pathophysiology of kidney lysosomes, experimentally induced iron overload models were employed. Iron overload was achieved through intraperitoneal injections of Fe-dextran (Imferon) in male rats, at different final iron concentrations (825 and 1650 mg/kg, single and double dose groups respectively). Controls were injected with dextran following a similar protocol. The animals were killed at different time points after the last injection. Subcellular fractionation studies of kidney homogenates were carried out by differential centrifugation and density gradient centrifugation. The kidney iron load was increased with both doses. Iron appeared to accumulate mainly in the lysosomes, bringing about distinct changes in the behaviour of the organelles as judged by subcellular fractionation studies. Lysosomes became more fragile and showed increased density. The extent of the above changes seemed to correlate with the extent and duration of iron accumulation and could be reversed when the iron load was reduced.

The facile detection of 1505G-->A in Gaucher patients with different phenotypes.

In Gaucher disease patients, over 100 disease-causing mutations have been identified. For identification of the 1504C-->T (R463C) mutation it is common to use PCR-restriction fragmentation analysis using the restriction enzyme MspI. In the present study we investigated the reliability of this approach because accurate determination of genotypes is important in genotype-phenotype correlations. A simple modification, i.e. using the restriction enzyme HphI instead of MspI, revealed that type I and II Gaucher disease patients who had previously been identified as carrying the 1504C-->T mutation in fact carried the 1505G-->A (IVS10(-1)G-->A) mutation. Sequencing of the appropriate fragment confirmed this. The PCR method easily differentiates between these two mutations in Gaucher disease patients, thus circumventing the need for sequencing procedures. The phenotypes of the patients found to be carrying the 1505G-->A mutation are also described.

Plasma tumor necrosis factor-a (TNF-a) levels in Gaucher disease.

Tumor necrosis factor-a (TNF-a) levels were measured in the plasma of patients with different types of Gaucher disease (GD) and patients with other lysosomal storage diseases. The highest TNF-a levels were observed in the most severe neuronopathic type of GD, exceeding those found in healthy individuals as well as patients with other lysosomal disorders. Type I GD cases showed a wide range of TNF-a levels ranging from normal to 2.5 x the highest control value. TNF-a is a pleiotropic cytokine produced mainly by activated macrophages. Our data suggest that it may play a role in the pathophysiology of GD disease.

Chitotriosidase in neonates with fungal and bacterial infections.

Increased plasma and/or urine chitotriosidase activity was found in neonates with fungal infection changing in parallel with their clinical condition. Increased levels were also found in neonates with bacterial infection. Chitotriosidase activity increase is not a response specific to fungi, but serial assays could monitor the course of neonatal fungal infection.

Pregnancy in Gaucher disease.

An 18-year old woman with type I Gaucher disease and two uncomplicated pregnancies is described. Although she experienced one miscarriage and pregnancy was associated with exaggeration of the clinical symptoms, leading to the diagnosis of the disorder, both her 2nd and 3rd pregnancies were uneventful and deterioration of her clinical situation was not observed. The issue of criteria for risk assessment in pregnancy of type I Gaucher disease patients is addressed.

Phenotypic variability of mannosidosis type II: report of two Greek siblings.

Two patients, a 13-year-old boy and his 24-year-old sister, were diagnosed as mannosidosis type II cases, on the basis of both presenting extremely reduced plasma and white blood cell acid-alpha-mannosidase are reported. With the exception of mental retardation and neurosensory deafness the two siblings manifested a wide phenotypic variability. The boy had several facial features indicating a lysosomal storage disorder, as well as spondylolisthesis. His sister, apart from heavy eyebrows and lower jaw prognathism appeared normal.

Lysosomal storage diseases in Greece.

Over the last 13 years 2745 patients from all over Greece suspected to have a lysosomal storage disorder were referred to the Institute of Child Health. 1581 of those were suspected of having a mucopolysaccharidosis (MPS). 94 cases (3.42% of the total referrals) were positive: 36 patients with MPS, 6 with mucolipidosis (1 type I, 1 type II and 4 type III) and 3 with mannosidosis. Sanfilippo B was not only the most frequent type III MPS but also the most frequent MPS identified in our study. Sphingolipidoses and other lysosomal disorders were diagnosed in 47 cases and non-lysosomal disorders in 19 cases. In our experience Gaucher disease, Sanfilippo B and Hunter syndrome are the most frequent lysosomal disorders in Greece accounting for 23.4%, 17.0% and 7.6% respectively of all diagnosed cases. 13% of the patients originated from Thessaly including 5/16 Sanfilippo B, 2/3 Morquio B, 2/3 Maroteaux-Lamy, 2/6 Metachromatic leukodystrophy and 2/12 Gaucher type 1.