Clemastine/tamoxifen hybrids as easily accessible antileishmanial drug leads.

A library of hybrid molecules is developed based on the common chemical features shared by clemastine and tamoxifen both of which are well known for their antileishmanial activities. In the initial screening against Leishmania major and L. amazonensis promastigotes, as well as cytotoxicity assays using HepG2 cells, several hybrids showed submicromolar activity against the parasite and no toxicity against human cells. The compounds with an EC50 < 2 µM against promastigotes of both species and a selectivity index >10 were further characterized against intracellular amastigotes as well as promastigotes of species that cause both visceral and cutaneous leishmaniasis, such as L. infantum and L. braziliensis, respectively. These sequential screenings revealed the high pan-activity of this class of molecules against these species, with several compounds displaying an EC50 ≤ 2 µM against both promastigotes and intracellular amastigotes. Two of them were identified as the potential templates for lead optimization of this series having shown the highest activities against all species in both stages of parasite. The present findings can serve as a good starting point in the search for novel antileishmanial compounds that are easy to access and highly active.

Expanding the product portfolio of carbon dioxide and hydrogen-based gas fermentation with an evolved strain of Clostridium carboxidivorans.

CO2:H2-based gas fermentation with acetogenic Clostridium species are at an early stage of development. This work exploited the Adaptive Laboratory Evolution technique to improve the growth of C. carboxidivorans P7 on CO2 and H2. An adapted strain with decreased growth lag phase and improved biomass production was obtained. Genomic analysis revealed a conserved frameshift mutation in the catalytic subunit of the hexameric hydrogenase gene. The resulted truncated protein variant, most likely lacking its functionality, suggests that other hydrogenases might be more efficient for H2-based growth of this strain. Furthermore, the adapted strain generated hexanol as primary fermentation product. For the first time, hexanol was produced directly from CO2:H2 blend, achieving the highest maximum productivity reported so far via gas fermentation. Traces of valerate, pentanol, eptanol and octanol were observed in the fermentation broth. The adapted strain shows promising to enrich the product spectrum targetable by future gas fermentation processes.

Environmental electroactive consortia as reusable biosensing element for freshwater toxicity monitoring.

The development of tools to monitor water quality is mandatory in a scenario where clean water resources are decreasing. Here, the biosensing capability of an electroactive river sediment consortium was tested towards three model contaminants (glutaraldehyde, nickel(II) and chromium(III)). The proposed biosensor is a small membrane-less single chamber Microbial Fuel Cell (MFC), fabricated by 3D printing. Its semi-continuous mode of operation resulted in long-term current profile stability and reproducibility. A linear trend of response was obtained for glutaraldehyde in a concentration range of 5-1000 ppm. After the recovery of the electroactive consortium activity, the MFC-based biosensors were shown to be sensitive towards Ni(II) and Cr(III), at concentrations above 2 mg L-1. To effectively analyze biosensor response, a novel algorithm was proposed, offering advantages for the realization of energy-saving protocols for MFC-biosensor data transmission. Implementation of the device and method, from laboratory test to real environment, can offer a low cost in situ system for detection of water contaminants.

Clinical and personality features of allodynic migraine.

Cutaneous allodynia (CA) is a frequent complaint during migraine attacks, recently associated with migraine transformation as well as psychiatric comorbidities. The aim of our study was to define the clinical features of allodynic migraineurs, in particular, the relationship between CA and personality profile. Between October 2008 and December 2009, 410 migraineurs admitted for the first time to our Headache Center underwent Allodynia Symptom Checklist, MIgraine DIsability Assessment Scale (MIDAS) and psychometric tests [Tridimensional Personality Questionnaire (TPQ), Toronto Alexithymia Scale, State and Trait Anxiety Inventory (STAI Y 1-2), and Beck Depression Inventory (BDI)]. Allodynia was present in 63% of cases, mostly in females. In CA patients, an association with female sex, chronic migraine, higher values of MIDAS, BDI, harm avoidance (HA, a TPQ dimension) and STAI Y-2 was found. Interestingly, CA appears to be associated with depression and a particular personality profile characterized by higher values of HA, suggesting an involvement of the serotonergic system in the development of CA in migraine. In conclusion, CA is associated with progression of migraine and it could be a marker of psychiatric comorbidities, in particular, depression and anxious trait.

Non-Alcoholic Wernicke Encephalopathy: MR Imaging and Review of the Literature.

We describe a patient with non-alcoholic Wernicke's encephalopathy caused by long-term parenteral nutrition. The diagnosis is based on clinical and magnetic resonance findings. We also reviewed the literature review in typical and atypical findings at MR examination.

A possible role of ID-Migraine in the emergency department: study of an emergency department out-patient population.

Headache symptoms account for 1-3% of admissions to an emergency department (ED). Most patients affected by a primary headache (PH) have migraine, although they are often misdiagnosed as 'headache not otherwise specified'. We investigated the possibility of using ID-Migraine (ID-M) to improve migraine recognition in the ED setting. We planned a pilot study involving ED out-patients with a diagnosis of PH. Diagnoses of a blinded headache expert were subsequently matched with the ID-M results. We tested ID-M on 230 patients (199 PH, 31 secondary headaches). Considering only PH, ID-M exhibited a sensitivity of 0.94 and specificity of 0.83 with a positive predictive value (PPV) of 0.99. The ID-M is a simple migraine screener with high sensitivity, high specificity and high PPV, even in an ED-derived population. Methodical use of this tool in an ED setting may, once a secondary headache has been excluded, lead to rapid diagnosis of migraine.

Psychophysiological aspects of voluntary skilled movement after stroke: a follow-up study.

OBJECTIVES: The aim of the study was to follow the psychophysiological evolution of a self-paced voluntary skilled movement in hemiparetic subjects after ischemic stroke by means of a skilled performance task (SPT). The task consisted in starting a sweep of an oscilloscope trace by pushing one button with the left index finger (trigger point), and in stopping it within a central area on the oscilloscope screen, between 40 and 60 ms (correct performance) after the start of the sweep, by pushing the other button with the right index finger. A SPT yields a considerable amount of information on the electrophysiological components, which reflect pre-programming activity (Bereitschaftspotential--BP), control strategies (Skilled Performance Positivity--SPP) and behavioural response (Correct Performances). The study was also aimed at detecting any longitudinal changes in the psychophysiological pattern, as evaluated by the clinical examination and specific motility scales, that parallel motor recovery. METHODS: Movement related potentials (MRPs) were recorded in 12 control subjects and 9 patients in the acute phase, before the start of neurorehabilitation (time 0), when the patients were able to execute an index finger press with the affected hand. The patients (mean age = 62.33 years, SD = 8.17) presented a mild to moderate central arm paresis caused by a first-ever unilateral supratentorial and subcortical ischemic lesion. The subsequent recordings were carried out respectively 3, 9 and 12 months later. RESULTS: At the first recording, hemiparetic patients achieved a significantly lower percentage of correct performances and had a lower BP amplitude than controls (p < 0.001); SPP was absent. The number of correct performances did not improve significantly during the subsequent recordings. BP amplitude showed a mild increase in the second, third and fourth recordings (p < 0.05), while SPP amplitude revealed a slight improvement at the second and a marked improvement at the third and fourth recordings, when there was no longer a statistically significant difference from controls. CONCLUSIONS: Our findings point to an early recovery of pre-programming activity and a delayed improvement in control activity. The delayed development of control activity in the absence of procedural learning, i.e. skill learning through practice, forces patients to exploit attentional strategies to compensate for their procedural learning impairment. SPT shows that the efficacy of physical therapy aimed at motor ability recovery in hemiparetic patients does not keep up with the slow recovery process of an automatic motor level.

Massive peripheral nerve hypertrophy in a patient with chronic inflammatory demyelinating polyradiculoneuropathy.

We describe a male patient with chronic inflammatory demyelinating polyradiculoneuropathy presenting extensive diffuse hypertrophy of the nerve roots of peripheral nerves. Since adolescence the patient has had a slow and progressive mainly distal loss of sensitivity and muscle weakness in all four limbs. He presented with diffuse muscle atrophy with enlarged palpable nerve trunks. Electromyography disclosed impaired sensory and motor responses in the bilateral median nerves and the right ulnar nerve. CSF examination showed elevated protein content, while MR scans depicted extensive hypertrophy of the spinal nerve roots. The patient benefitted from corticosteroid treatment.

Giant intracranial chordoma: neuroradiological and radiotherapeutic aspects.

We describe a rare case of giant intracranial chordoma, emphasizing the patient's long survival and his excellent response to radiotherapy that led to a progressive regression of neurological symptomatology up to disappearance, in the absence of cerebral white matter damages.

Cokriging optimization of monitoring network configuration based on fuzzy and non-fuzzy variogram evaluation.

A number of optimization approaches regarding monitoring network design and sampling optimization procedures have been reported in the literature. Cokriging Estimation Variance (CEV) is a useful optimization tool to determine the influence of the spatial configuration of monitoring networks on parameter estimations. It was used in order to derive a reduced configuration of a nitrate concentration monitoring well network. The reliability of the reduced monitoring configuration suffers from the uncertainties caused by the variographer's choices and several inherent assumptions. These uncertainties can be described considering the variogram parameters as fuzzy numbers and the uncertainties by means of membership functions. Fuzzy and non-fuzzy approaches were used to evaluate differences among well network configurations. Both approaches permitted estimates of acceptable levels of information loss for nitrate concentrations in the monitoring network of the aquifer of the Plain of Modena, Northern Italy. The fuzzy approach was found to require considerably more computational time and numbers of wells at comparable level of information loss.

A probabilistic methodology to assess the risk of groundwater quality degradation.

An approach to assess the risk of groundwater quality degradation with regard to fixed standards. based on Disjunctive Kriging (DK) is presented. The DK allows one to evaluate the Conditional Probability (CP) of overriding a given threshold of concentration of a pollutant at a given time, and at a generic point in a considered groundwater system. The result of such investigation over the considered area can be plotted in form of maps of spatial risk. By repeating this analysis at different times, several spatial risk maps will be produced, one for each considered time. By means of non-parametric statistics, the temporal trend of the CPs can be evaluated at every point of the considered area. The trend index, assessed by means of a sort of classification of the trend values obtained as described above, can be superimposed on the most recent values of the spatial risk (i.e.: the most recent values of probability). Consequently a classification of the risk of groundwater quality degradation results with which to weigh both the spatial distribution and the temporal behaviour of the probability to exceed a given standard threshold. The methodology has been applied to values of nitrate concentration sampled in the monitoring well network of the Modena plain, northern Italy. This area is characterised by intensive agricultural exploitation and hog breeding along with industrial and civil developments. The influence of agriculture on groundwater results in a high nitrate pollution that limits its use for potable purposes.

Diagnostic value of knee extension torque tracings in suspected anterior cruciate ligament tears.

The purpose of this study was to determine the diagnostic accuracy of knee extensor muscle torque tracings in patients suspected of having damage to the anterior cruciate ligament of the knee joint. The knee extensor torque tracings of 30 patients suspected of having anterior instability of the knee joint were reviewed independently for abnormalities believed to be associated with anterior cruciate ligament damage. These results were compared blindly with an arthroscopic evaluation. The diagnostic accuracy of the torque tracing approach was determined by calculating the prevalence, sensitivity, specificity, and positive and negative predictive values. The sensitivity and specificity were calculated to be 25.0% and 85.7%, respectively. These results suggest that the curve patterns examined in this article have poor diagnostic accuracy and are of little benefit as a clinical diagnostic aid.