Water quality and human health: A simple monitoring model of toxic cyanobacteria growth in highly variable Mediterranean hot dry environments.

Due to population growth, urbanization and economic development, demand for freshwater in urban areas is increasing throughout Europe. At the same time, climate change, eutrophication and pollution are affecting the availability of water supplies. Sicily, a big island in southern Italy, suffers from an increasing drought and consequently water shortage. In the last decades, in Sicilian freshwater reservoirs several Microcystis aeruginosa and more recently Planktothrix rubescens blooms were reported. The aims of the study were: (1) identify and quantify the occurring species of cyanobacteria (CB), (2) identify which parameters, among those investigated in the waters, could favor their growth, (3) set up a model to identify reservoirs that need continuous monitoring due to the presences, current or prospected, of cyanobacterial blooms and of microcystins, relevant for environmental and, consequentially, for human health. Fifteen artificial reservoirs among the large set of Sicilian artificial water bodies were selected and examined for physicochemical and microbiological characterization. Additional parameters were assessed, including the presence, identification and count of the cyanobacterial occurring species, the measurement of microcystins (MCs) levels and the search for the genes responsible for the toxins production. Principal Component Analysis (PCA) was used to relate environmental condition to cyanobacterial growth. Water quality was poor for very few parameters, suggesting common anthropic pressures, and PCA highlighted clusters of reservoirs vulnerable to hydrological conditions, related to semi-arid Mediterranean climate and to the use of the reservoir. In summer, bloom was detected in only one reservoir and different species was highlighted among the Cyanobacteria community. The only toxins detected were microcystins, although always well below the WHO reference value for drinking waters (1.0 µg/L). However, molecular analysis could not show the presence of potential cyanotoxins producers since a few numbers of cells among total could be sufficient to produce these low MCs levels but not enough high to be proved by the traditional molecular method applied. A simple environmental risk-based model, which accounts for the high variability of both cyanobacteria growth and cyanotoxins producing, is proposed as a cost-effective tool to evaluate the need for monitoring activities in reservoirs aimed to guarantee supplying waters safety.

The cortisol burden in elderly subjects with metabolic syndrome and its association with low-grade inflammation.

BACKGROUND: Elderly people are exposed to an increased load of stressful events and neuro-hormonal stimulation is a key finding in metabolic syndrome and its related disorders. AIMS: To determine the role of cortisol in elderly subjects, with or without metabolic syndrome (MetS), by means of a national multicentre observational study, AGICO (AGIng and Cortisol). METHODS: From 2012 to 2017, the AGICO study enrolled n.339 subjects (aged > 65), after obtaining their informed consent. The investigators assessed a cardio-metabolic panel (including electrocardiogram, carotid ultrasonography and echocardiography), the presence of MetS (on Adult Treatment Panel III criteria), a neurological examination (including brain imaging), and cortisol activity (using a consecutive collection of diurnal and nocturnal urine). RESULTS: In the patients presenting with MetS, the standardized diurnal and nocturnal cortisol excretion rates were 210.7 ± 145.5 and 173.7 ± 118.1 (mean ± standard deviation) µg/g creatinine/12 h; in those without MetS, the standardized diurnal and nocturnal cortisol excretion rates were 188.7 ± 92.7 and 144.1 ± 82.3 µg/g creatinine/12 h, respectively (nocturnal urinary cortisol in patients with MetS versus those without MetS p = 0.05, female patients with MetS vs female patients without MetS, p < 0.025). A significant positive correlation was found between the CRP levels and both the diurnal and nocturnal urinary cortisol levels with r = 0.187 (p < 0.025) and r = 0.411 (p < 0.00000001), respectively. DISCUSSION: The elderly patients with MetS showed a trend towards increased standardized nocturnal cortisol excretions, with particular regard to the female subjects. CONCLUSION: The positive correlation between cortisol excretion and low-grade inflammation suggests a common mechanism driving both hormonal and inflammatory changes.

Corrole and nucleophilic aromatic substitution are not incompatible: a novel route to 2,3-difunctionalized copper corrolates.

The insertion of a -NO2 group onto the corrole framework represents a key step for subsequent synthetic manipulation of the macrocycle based on the chemical versatility of such a functionality. Here we report results of the investigation of a copper 3-NO2-triarylcorrolate in nucleophilic aromatic substitution reactions with "active" methylene carbanions, namely diethyl malonate and diethyl 2-chloromalonate. Although similar reactions on nitroporphyrins afford chlorin derivatives, nucleophilic attack on carbon-2 of corrole produces 2,3-difunctionalized Cu corrolates in acceptable yields (ca. 30%), evidencing once again the erratic chemistry of this contracted porphyrinoid.

3-NO2-5,10,15-triarylcorrolato-Cu as a versatile platform for synthesis of novel 3-functionalized corrole derivatives.

ß-Nitrocorroles are potentially valuable platforms for the preparation of a wide range of more elaborated corrole derivatives possessing unique chemical functionalities and electronic properties. Here we report our results on the chemical manipulation of a copper 3-NO2-triarylcorrolate using different organic reactions, all involving the reduction of -NO2 to -NH2 at an early stage, followed by further transformations. By way of a ß-acylated copper corrolate, a novel corrole derivative bearing an alkyl azide group on the peripheral positions was obtained and exploited in the Huisgen 1,3-dipolar cycloaddition.

An observational study of venoplasty in patients with multiple sclerosis.

RATIONALE: It is estimated that some hundreds of Canadian patients with multiple sclerosis (MS) have journeyed abroad to avail themselves of 'liberation therapy' (venoplasty) following the initial report by Zamboni et al in 2009. That study also led to public pressure upon Departments of Health in Canadian Provinces to fund the procedure. The present study was done in order to advise the Government of Newfoundland and Labrador as to whether or not it should do so. METHODS: We conducted an observational study of 30 MS subjects who had submitted to venoplasty, using objective, semi-objective and subjective measures. RESULTS: Significant subjective improvement was reported by half of the subjects at three months, although the degree of perceived improvement was less at 12 months. The objective and semi-objective tests employed did not indicate improvement in any area over the one-year follow-up period. Seven of the 29 subjects in whom CT venography was performed at the end of the study year were found to have uni- or bilateral occlusion or >50% stenosis of at least one cervical draining vein, but they showed no deterioration in their clinical status compared to those in whom no venous occlusion nor stenosis was found. CONCLUSION: No objective improvement was found at one year in thirty MS subjects who had undergone venoplasty, although many reported a degree of subjective benefit.

The relation of ultraviolet radiation and multiple sclerosis in Newfoundland.

BACKGROUND: It has been thought that the occurrence of multiple sclerosis (MS) could be associated with daily ultraviolet exposure. In this study we investigated the geospatial association between average daily ultraviolet B (UVB) irradiance and MS prevalence in Newfoundland and Labrador (NL), Canada. METHODS: A complete list of patients diagnosed with MS in the province of NL was constructed. Places of habitation from birth to diagnosis were ascertained by mailout survey. RESULTS: A 74% rate of return on the survey results was obtained. A plot of the average daily erythemal UV over the available five years (1998-2002) shows that the distribution of MS follow a north-south gradient. Average daily UVB measurements are lower in the higher latitudes. A statistically significant negative correlation of MS incidence with erythemal UVB was found that is stronger than the correlation using latitude. This correlation appears to be strongest in the first year of life and declines when subsequent years are examined up to age ten. No significant correlation was found for the subjects' locale of habitation at the time of their first MS attack. CONCLUSIONS: This study suggests that UVB radiation may contribute to the pathogenesis of MS.

Cardinal directions for visual optic flow.

As we move through our environment, the flow of deforming images on the retinae provides a rich source of information about the three-dimensional structure of the external world and how to navigate through it. Recent evidence from psychophysical [1] [2] [3] [4], electrophysiological [5] [6] [7] [8] [9] and imaging [10] [11] studies suggests that there are neurons in the primate visual system - in the medial superior temporal cortex - that are specialised to respond to this type of complex 'optic flow' motion. In principle, optic flow could be encoded by a small number of neural mechanisms tuned to 'cardinal directions', including radial and circular motion [12] [13]. There is little support for this idea at present, however, from either physiological [6] [7] or psychophysical [14] research. We have measured the sensitivity of human subjects for detection of motion and for discrimination of motion direction over a wide and densely sampled range of complex motions. Average sensitivity was higher for inward and outward radial movement and for both directions of rotation, consistent with the existence of detectors tuned to these four types of motion. Principle component analysis revealed two clear components, one for radial stimuli (outward and inward) and the other for circular stimuli (clockwise and counter-clock-wise). The results imply that the mechanisms that analyse optic flow in humans tend to be tuned to the cardinal axes of radial and rotational motion.

Clinical guidelines as plans--an ontological theory.

OBJECTIVE: Clinical guidelines are special types of plans realized by collective agents. We provide an ontological theory of such plans that is designed to support the construction of a framework in which guideline-based information systems can be employed in the management of workflow in health care organizations. METHOD: The framework we propose allows us to represent, in formal terms, how clinical guidelines are realized through the actions of individuals or ganized into teams. We provide various levels of implementation representing different levels of conformity on the part of health care organizations. RESULT: Implementations built in conformity with our framework are marked by two dimensions of flexibility that are designed to make them more likely to be accepted by health care professionals than standard guideline-based management systems. They do justice to the fact 1) that responsibilities within a health care organization are widely shared, and 2) that health care professionals may on different occasions be non-compliant with guidelines for a variety of well justified reasons. CONCLUSION: The advantage of the framework lies in its built-in flexibility, its sensitivity to clinical context, and its ability to use inference tools based on a robust ontology. One disadvantage lies in its complicated implementation.

The M2DM Project--the experience of two Italian clinical sites with clinical evaluation of a multi-access service for the management of diabetes mellitus patients.

OBJECTIVES: This paper presents a multi-access service for the management of diabetes mellitus patients and the results of its assessment in two Italian clinical sites. METHODS: The service was evaluated for one year in order to prove the advantages of these kind of systems from different points of view. In this paper the clinical, usability and technical outcomes are presented. RESULTS: The evaluation results show that, thanks to the high flexibility of the implemented service, the telemedicine management of diabetes patients is feasible, well accepted by patients and clinically effective. However, in Italy the problem of quantifying the reimbursement rate of telematic services and the impact they have on the organization are factors that may hamper their introduction in routine clinical practice. CONCLUSIONS: The evaluation study showed that the telemedicine intervention has been satisfactory both for physicians because it allows to constantly monitor the patients' blood glucose level and for patients because it strengthens their motivation to self-monitor the metabolic situation.

Onset of ulcerative colitis after thyrotoxicosis: a case report and review of the literature.

OBJECTIVE: Ulcerative colitis is a chronic disease that could be triggered by acute stressful events, such as gastrointestinal infections or emotional stress. PATIENTS AND METHODS: We reported the case of the onset of an ulcerative colitis after a thyrotoxicosis crisis and reviewed the literature about the relationships between thyroid dysfunctions and ulcerative colitis. RESULTS: A 38-year-old woman was diagnosed with ulcerative colitis after her third thyrotoxicosis crisis, two years after the diagnosis of Graves' disease. In this case, thyrotoxicosis acted as a trigger for ulcerative colitis onset. CONCLUSIONS: Hyperthyroidism could be a trigger able to elicit ulcerative colitis in susceptible patients.

Long-term cardiac sequelae in operable breast cancer patients given adjuvant chemotherapy with or without doxorubicin and breast irradiation.

PURPOSE: To investigate long-term cardiac sequelae associated with anthracycline use in adjuvant chemotherapy of patients with early breast cancer. PATIENTS AND METHODS: All 1,000 patients from three prospective trials of adjuvant chemotherapy containing doxorubicin (n = 637, median total dose of 294 mg/m(2)) or not containing the anthracycline (cyclophosphamide, methotrexate, and fluorouracil [CMF] regimen alone, n = 363) were analyzed for the relative incidence of congestive heart failure (CHF) and myocardial infarction (MI) during 14 years of follow-up. The 462 women continuously free of disease as of February 1996 were recalled, and 355 consented to undergo evaluation including 12-lead ECG and cardiac ultrasound with determination of left ventricular ejection fraction (LVEF) to assess the relative incidence of abnormalities in long-term survivors. RESULTS: Among the 1,000 patients, there were six cases of CHF and three cases of MI. Cumulative cardiac mortality accounted for 0.4% (doxorubicin-treated = 0.6%; CMF-treated = 0). Eighteen (5%) of the 355 patients undergoing cardiac evaluation after median 11 years of follow-up presented systolic dysfunction as defined by pathologic (< 50%, n = 8) or borderline (50% to 55%, n = 10) LVEF. Systolic dysfunction was higher in doxorubicin-treated (15 of 192; 8%) than in CMF-treated patients (three of 150; 2%). Breast irradiation had a significant impact on the occurrence of early CHF (four of 116; 3%), but not on systolic dysfunctions. CONCLUSION: At longer than 10 years of follow-up, the use of doxorubicin at a total dose commonly applied in regimens of adjuvant chemotherapy does not lead to cardiac clinical sequelae that counter-balance the benefit of treatment in patients with operable breast cancer who may be cured of their disease.

Incidence and prevalence of multiple sclerosis in Newfoundland and Labrador.

BACKGROUND: The incidence and prevalence of multiple sclerosis (MS) in Newfoundland and Labrador (NL) had been reported in 1984 and was considered to be relatively low at that time. This study revisits the incidence and prevalence of MS in NL for the year 2001. METHODS: Case searches through patient files of neurologists in NL were conducted. A complete list of patients billed for MS in NL between 1996 and 2003 was obtained and all cases were confirmed via chart review. RESULTS: There were 493 living MS patients yielding a prevalence of 94.4/100,000 which is significantly higher than previously reported. Of the living patients, 330 had relapsing remitting (RRMS), 94 had secondary progressive, 66 had primary progressive (PPMS) and three had unspecified MS. The total female to male ratio was 2.7:1. There was no difference between the female to male ratios for RRMS vs PPMS. Patients with PPMS had a later onset compared to RRMS (p<0.00001). Yearly incidences were relatively constant from 1994 to 2001 (5.6/100,000). Significant delays between first symptoms and final diagnosis were common and the delay time has not changed over the past 15 years. A prevalence of 88.9/100,000 was estimated from survival and incidence trends and was not significantly different than the measured prevalence (p=0.38). CONCLUSIONS: The increase in incidence and prevalence are accounted for through both better access to diagnostic facilities and more practicing neurologists. The revised prevalence and incidence are more in keeping with recently reported values throughout Canada.

Multiple sclerosis in Newfoundland and Labrador--a model for disease prevalence.

BACKGROUND: Newfoundland and Labrador, Canada, have been almost exclusively populated by immigrants from southwest England and southeast Ireland. The province's population grew largely by natural increase from 20,000 people in 1835 to half a million at present. Very little interregional migration occurred within the province. This uniquely-populated region and its subsequent founder effect provide the basis to develop models of disease prevalence. OBJECTIVES: To develop a model for the regional prevalence of multiple sclerosis (MS), accounting for settlement patterns and geographic location (latitude). METHODS: All living MS patients with confirmed addresses (438 patients) in the province were mailed a survey requesting their place of birth. Regional prevalences were calculated from a 75% rate of return of the survey. Theoretical regional prevalences were proportionally calculated from the source prevalences of southwest England, southeast Ireland, Scotland and the Channel Islands based on settlement patterns. These theoretical regional prevalences were corrected for geographical variations of latitude based on observations in the United Kingdom. Theoretical and actual regional prevalences were compared. RESULTS: When actual regional prevalences were compared with theoretical prevalences, very little variation was noted, especially after correcting for variation in latitude. CONCLUSION: A regional variation in MS prevalence is noted in the island portion of Newfoundland and Labrador. This regional variation can be modeled by using both migration patterns and latitudinal position. This model demonstrates that the prevalence of MS is influenced by both genetic and environmental contributions.

[Melanoma of the forearm. A historical case report]. / Mélanome de l'avant-bras. A propos d'un cas historique.

We present the case of a melanoma of the forearm notable for its depth (Breslow index 35 mm), due to a longstanding lack of interest and care by the patient as well as her physician. Because of systemic metastases, only palliative treatment, consisting of an excision of the lesion for local hygiene, could be offered. The patient survived for only three months. This case illustrates the absolute necessity to remove without delay, any cutaneous tumor that resembles a melanoma, in order to avoid diagnosis being made at a late stage when curative treatment cannot be performed.

Analgesic, antiulcer, antithrombotic drugs and organ damage: a population-based case-control study.

AIM: Oral medication is of paramount importance for pain treatment. Analgesics, antiulcer (AUDs) and antithrombotic drugs (ATDs) are often coprescribed in elderly people. Non-steroidal anti-inflammatory drugs (NSAIDs) require AUDs to lower the risk of peptic ulcer, and potentially interfere with ATDs. The aim of this study was to quantify the prevalence of NSAID use in patients with gastrointestinal, cardiac or kidney damage in the year 2013, compared to the general population. METHODS: We performed a population-based case-control study in the Republic of San Marino to evaluate the Odds-Ratios for upper gastrointestinal damage (gastroduodenal ulcers and/or erosions, GUE), ischemic heart disease (IHD), heart failure (HF), and renal function impairment (assessed using the CKD-EPI formula), in people who had taken AUDs, ATDs, or NSAIDs in the previous 90 days, versus people who had not taken such drugs in the same period of time. RESULTS: We found that AUDs decreased the OR for GUE (OR: 0.762; CI:0.598-0.972), while ATDs and NSAIDs increased the risk (OR: 1.238 and CI: 0.935-1.683; OR:1.203 and CI:0.909-1.592, respectively). NSAIDs seemed to increase the risk of IHD, although this was not statistically significant (OR=1.464; CI=0.592-3.621). AUDs and ATDs significantly increased the risk of renal function impairment (OR=1.369 and CI=1.187-1.579; OR=1.818 and CI=1.578-2.095, respectively), while this effect was not observed for NSAIDs. CONCLUSION: NSAIDs may induce gastrointestinal and cardiovascular damage, not only by themselves, but also when used concomitantly with common medications such as AUDs or ATDs, due to additive and/or synergistic effects. We performed a "pragmatic" analysis of the association of organ damage with use of NSAIDs/AUDs/ATDs, including patient age, treatment duration and dose, to allow for an immediate application of our findings to everyday clinical practice.

Seroprevalence of hepatitis A virus and Helicobacter pylori infections in the general population of a developed European country (the San Marino study): evidence for similar pattern of spread.

OBJECTIVE: To evaluate the role of faecal-oral transmission in the spread of Helicobacter pylori. DESIGN: A cross-sectional comparison of the patterns of hepatitis A and H. pylori seropositivity. METHODS: At interview, blood samples and questionnaire data were collected from a random sample of 1528 healthy subjects aged 20-85 years from the Republic of San Marino. Serum samples from each subject were then tested for anti-H. pylori and anti-hepatitis A antibodies. RESULTS: Overall, 529 of 670 H. pylori-seropositive subjects (78.9%) and 460 of 858 H. pylori-seronegative subjects (53.6%) were hepatitis A seropositive (P<0.01; odds ratio=3.2; confidence interval 95%=2.6-4.1). This association remained after adjustment by a multiple logistic regression analysis for the confounding effect of age and length of schooling, as surrogate for socio-economic status (OR=2.0; CI 95%=1.3-3.3). The age-specific prevalence curves for H. pylori and hepatitis A infections showed a parallel increase by age, although to a lesser extent for H. pylori. CONCLUSION: These findings provide evidence that in the community studied H. pylori may have spread in a manner similar to that of hepatitis A.

An influence diagram for assessing GVHD prophylaxis after bone marrow transplantation in children.

Graft-versus-host disease (GVHD) represents one of the major complications of allogeneic bone marrow transplantation (BMT). Nevertheless, the occurrence of mild GVHD could be desirable in high-risk leukemic patients, due to a relapse-preventing effect known as the graft-versus-leukemia (GVL) effect. Given that different prophylactic interventions are available to prevent GVHD development, the decision problem consists in assessing both type and dosage of the drugs in order to avoid or induce GVHD, according to the specific patient's condition. The decision problem can be represented and solved by using an influence diagram. The choice of this formalism allows using new available methods for building and updating the model of the decision problem. The qualitative structure of the model and the conditional probabilities were first derived by combining literature results with a medical expert's judgement. More specifically, probabilities were initially assigned as ranges rather than as point values. Then, conditional probabilities were updated, by using a learning algorithm, as new cases became available. The authors analyzed 50 cases of pediatric patients affected by either malignant or nonmalignant diseases, undergoing BMT and receiving GVHD prophylaxis. They used the first 25 cases to adjust the initially assigned conditional probabilities, then checked the model obtained on the remaining patients. The overall performance for GVHD prediction was about 80%.

Effect of Helicobacter pylori infection, age and epithelial cell turnover in a general population at high risk for gastric cancer.

BACKGROUND: H. pylori and age are two known risk factors for atrophic gastritis and high epithelial cell turnover may be an indicator for preneoplastic changes in the stomach. We searched for an association between H. pylori, age and gastritis in the general population together with the proliferative state into the antral mucosa. METHODS: We examined gastric biopsies from antrum and corpus of 117 consecutive volunteers which were endoscoped during a population study in San Marino. H. pylori status was determined by serum IgG antibodies, rapid urease test on biopsies and histology. Presence of gastritis and grading of inflammation, activity, intestinal metaplasia and atrophy were ascertained using Sydney System. On a subsample of 36 subjects without endoscopic lesions we performed an immunohistochemical study on gastric cell proliferation using PCNA. A computer-aided count was made on stained epithelial cells to evaluate labeling index. Statistical analysis was performed using chi 2 test and linear regression. RESULTS: Inflammatory infiltrate (both activity and mononuclear cells), (p < 0.0001) and intestinal metaplasia (p < 0.004) were significantly higher in H. pylori positive subjects. Atrophic gastritis was present in 82% H. pylori positive subjects vs 17.6% (p < 0.0001). Labeling Index was significantly higher in H. pylori positive subjects (p < 0.005) and it was correlated with inflammation and atrophy (p = 0.001). Elderly H. pylori negative subjects have a lower cell turnover (p = 0.006) but H. pylori infected subjects do not show any decrease of Labeling Index with age. CONCLUSIONS: In the general population of an area with high gastric cancer rate, H. pylori infection is associated with atrophic gastritis and with hyperproliferative gastric cell state. These conditions are present either in young and old age and increase the neoplastic risk of gastric mucosa.

Seizure exacerbation and developmental regression with carbamazepine.

BACKGROUND: Unexpected exacerbation of seizures may occur following initiation of treatment with carbamazepine (CBZ). We reviewed the occurrence of such reactions in our patient population at a tertiary care children's hospital. METHODS: A retrospective analysis of our clinic database identified 129/691 (18.6%) patients with epilepsy treated with CBZ, as monotherapy. 38/129 children were later switched to another drug. In 11/38 (28.5%) clinical and/or EEG deterioration was observed. Two patients identified at another institution with similar exacerbation were also included in our analysis. We report on the findings in these 13 cases. RESULTS: Two groups were identified: Group I--6 patients with normal neurological exam, normal EEG background, and a diagnosis of idiopathic generalized epilepsy. Group II--7 patients with an abnormal neurological exam and/or abnormal EEG background. Following introduction of CBZ therapy, worsening of preexisting seizures, appearance of new seizure types, behavioral regression, and accompanying EEG deterioration were reported in both groups. Dramatic improvement in seizure control occurred, following withdrawal of CBZ and substitution of another anticonvulsant. CONCLUSION: Physicians treating epilepsy must be aware that CBZ can exacerbate seizures, and cause developmental regression in children. Careful patient selection, when choosing CBZ as treatment, and prompt recognition of clinical deterioration and intervention, may help avoid or reverse these paradoxical reactions.