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Background Previous small observational studies have suggested a potential association of proprotein convertase subtilisin kexin type 9 (PCSK9) and platelet reactivity. However, the role of the PCSK9 inhibitor alirocumab on platelet aggregation among patients with acute myocardial infarction (AMI) remains unknown. Purpose We investigated the effect of alirocumab on P2Y12 reaction unit (PRU) on top of high-intensity statin therapy among AMI patients receiving dual antiplatelet therapy (DAPT) with a potent P2Y12 inhibitor (ticagrelor or prasugrel). Methods This was a pre-specified, powered, pharmacodynamic substudy nested within the PACMAN (effects of the PSCK9 antibody AliroCuMab on coronary Atherosclerosis in patieNts with Acute Myocardial Infarction) trial, a randomized, double-blind trial comparing biweekly alirocumab (150mg) versus placebo in AMI patients undergoing percutaneous coronary intervention (PCI). Patients recruited at Bern University Hospital, receiving DAPT with either ticagrelor or prasugrel at 4 weeks and adherent to the study drug (alirocumab or placebo) were analyzed for the current study. The VerifyNow P2Y12 point-of-care assays were used to measure PRU at baseline (i.e. before first study drug administration), 4 weeks, and 52 weeks after study drug administration (higher PRU levels indicating greater platelet aggregation). The primary endpoint was PRU at 4 weeks. Results Among 139 randomized patients (mean age 58.2 years [SD, 9.5], 21 [15.0%] women, mean LDL-C level 150.6mg/dL [SD, 30.9]), baseline characteristics were well balanced between groups including baseline PRU (50.0 [IQR, 120.0] in the alirocumab group vs. 62.0 [IQR, 122.0] in the placebo group, P=0.75). At 4 weeks, mean LDL-C was significantly lower in the alirocumab group (23.5 [SD, 23.7] mg/dL vs. 74.4 [SD, 30.5] mg/dL, P Conclusion Among AMI patients receiving DAPT with potent P2Y12 inhibitors, alirocumab had no significant effect on platelet function as assessed by PRU. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Bern University Hospital

The purpose of this review is to discuss cardiovascular mortality as clinical outcome in the setting of both acute and chronic coronary syndromes (ACS and CCS) with a focus on the clinical evidence supporting the mortality benefit of ticagrelor across multiple subpopulations.Papers considered for this review were retrieved from a PubMed search, using different combinations of keywords (e.g., mortality AND coronary syndrome AND dual antiplatelet therapy AND ticagrelor), without limitations in terms of publication date and language.Prevention of ischemic events and death is of outmost relevance in patients with ACS and CCS, given the high rate of recurrence of such events and fatalities. Owing to the evolving nature of patients with CCS, characterized by a broad spectrum of clinical presentations and previous medical history, as well as the advances in the therapeutic and invasive management of ACS, greater attention to the rate of hard clinical outcomes, improvement in the long-term prognosis, and reduction in the residual risk of recurrent events are increasingly reported among cardiologists. Dual antiplatelet therapy (DAPT) is the cornerstone of antithrombotic therapy aimed at lowering the rate of ischemic events and death in patients treated both conservatively and invasively after ACS, as well as improving prognosis in patients with CCS. Significant differences are emerging among oral P2Y12 inhibitors with regards to mortality benefit.Ticagrelor is an effective and well-tolerated option to attain a meaningful and clinically relevant reduction in cardiovascular mortality in both acute and chronic settings across a broad range of high-risk patient subpopulations with an acceptable payoff in terms of bleeding risk.

The detection and attribution of methane in aquifers overlying oil and gas reservoirs has recently gained increasing attention internationally. The Surat Basin, in the Great Artesian Basin (GAB), Australia, hosts a coal seam gas (CSG) reservoir, with feedlots, town water supply, mines and agriculture that extract groundwater from aquifers that underly and overly the gas reservoir. This study aimed to use a multi-isotopic approach to differentiate biogenic methane generated in situ in GAB aquifers and the Condamine Alluvium, from the biogenic CSG produced from the underlying Walloon Coal Measures reservoir, to understand if gas had migrated or not. Dissolved methane (0.001 to 160 mg/l) and total methane concentrations (up to 91,818 ppmv) were measured using closed sampling methods and were higher than from open direct fill sampling (0.001 to 25.4 mg/l), especially in gassy bores that contain dissolved methane above 10 to 13 mg/l. The CSG production waters and a gassy overlying aquifer bore had the most depleted water isotopes, and also the most enriched δ

Background There is an increasing amount of evidence suggesting multiple fatal complications in Takotsubo Syndrome. However, findings on the long-term outcome are scarce and show inconsistent evidence. Methods This is a single-center study of long-term prognosis in Takotsubo patients admitted from September 2006 to August 2019. We investigated the clinical features, prognostic factors and outcome of patients with Takotsubo syndrome. Furthermore, survivors and non-survivors and patients with a different cause of death were compared. Results Overall, 147 patients were included in the study. The mean age was 70 years (±12,3), and 85% of the study population were women. Forty-nine Takotsubo patients (33,3%) died during the follow-up, with a median of 126 months. The most common cause of death was a non-cardiac cause (71,4% of all deaths), especially malignancies (26,5% of all deaths). Moreover, non-survivors were older and more often men with more comorbidities (chronic kidney disease, malignancy). Patients who died because of cardiovascular disease were older and more often women than patients who died due to non-cardiovascular cause. Age showed to be the only independent prognostic factor of cardiovascular mortality (HR=1,11, CI: 0,99–1,25, p=0,05). Female gender (HR=0,32, CI: 0,16–0,64, p Conclusion Long-term prognosis of TTS patients is not favourable, mainly due to non-cardiac comorbidities. Hence, consequent outpatient care in relatively short time intervals after TTS event based on risk factor control and early detection of malignancies seems mandatory. Funding Acknowledgement Type of funding sources: None.

The Surat Basin hosts various industries that extract groundwater including coal seam gas (CSG), feedlots, and agriculture. With water drawdown, gas has been observed in some bores drawing groundwater from different aquifers across the Basin. While methane can occur naturally in aquifers, biogenic CSG has been extracted from the Walloon Coal Measures raising questions on the sources of gas in overlying aquifers. Current standard monitoring uses a direct fill approach to measure dissolved methane concentrations in vials; however, this approach may lose gas present above solubility levels. Water and gas sampling was performed on bores in the Springbok, Gubberamunda, Mooga, Hutton, and Precipice Sandstones, the Orallo Formation, and the Condamine Alluvium. Water bores and CSG production wells from the Walloon Coal Measures were also sampled. We compared direct fill with a closed sampling method for dissolved gas, plus a method for sampling the total free and dissolved gas in the field. Higher dissolved and total methane concentrations were measured using closed sampling methods, especially in gassy bores. The majority of our sampled aquifer gases and waters have stable isotopic signatures distinct from CSG, where methane had likely been formed insitu in shallow aquifers by primary microbial CO2 reduction or fermentation processes. In several gassy bores, the source of the methane could not be clearly identified. This study indicates that (1) current monitoring methods may be underestimating methane concentrations above identified thresholds especially in gassy bores and (2) a combination of isotopic techniques may distinguish methane sources and interaquifer disconnectivity in the majority of cases.

distinguono in benigni e maligni e possono essere primari o secondari a processi metastatici. Sono relativamente rari e la loro incidenza dipende dalla modalità con cui vengono rilevati. Molte serie autoptiche riportano una incidenza variabile tra 0.0017% e 0.28%, mentre nella popolazione sottoposta ad indagine ecografica l’incidenza varia da 017% a 0.2% (10). Il miglioramento delle tecniche diagnostiche ha determinato un aumento della incidenza dei tumori cardiaci pediatrici, passando da 0.06% dei primi anni ’80 a 0.32% nella metà degli anni ‘90 (2). La maggior parte di tumori cardiaci primitivi che si riscontrano in età pediatrica sono per lo più benigni e costituiscono circa il 90% di tutte le forme, mentre i tumori maligni sono il 10% (3,10,12,19). I tumori maligni secondari sono più diffusi di quanto non lo siano i primitivi, in particolare sono frequenti i secondarismi di natura renale (ad es. il tumore di Wilms). Nella vita fetale e nell’infanzia il tumore cardiaco più comune è il rabdomioma, mentre è raro il mixoma, il più frequente invece in età adulta. Altri tumori in ordine di frequenza nell’infanzia sono il teratoma, il fibroma e l’emangioma. Il rabdomioma e il teratoma del pericardio rappresentano il 70% dei tumori primari del cuore nel feto, nel neonato e nei bambini (9). Sintomatologia La sintomatologia in genere è legata alle caratteristiche del tumore ma si possono evidenziare delle manifestazioni cliniche comuni. Nella vita fetale molto frequentemente le neoplasie cardiache possono manifestarsi con aritmie, insufficienza cardiaca congestizia e idrope. Nella vita postnatale si presentano, nella maggior parte dei casi, con cianosi, difficoltà respiratoria, disfunzione miocardica, insufficienza valvolare, aritmie e fenomeni tromboembolici. In alcuni casi si può verificare una morte improvvisa per aritmie o per ostruzione delle valvole atrioventricolari o dell’efflusso ventricolare (1,3,10-11,14). Sintomi aspecifici, come si verifica anche in presenza di tumori cardiaci dell’adulto, possono essere perdita di peso, stanchezza, febbre, sensazione di malessere. Inoltre i tumori possono dare alterazioni ematologiche, tra cui anemia, policitemia, leucocitosi, trombocitosi ed elevata velocità di sedimentazione per la produzione di interleuchine infiammatorie (ad es. IL-6) (4,10).

The anatomic relationship between major neurological and vascular structures in the neck places any patient undergoing cervical spine surgery at risk of complications during the surgical exposure for degenerative, traumatic and oncologic pathologies. A knowledge of anatomy and careful technique during dissection are essential to prevent and treat injures if they occur. In this paper we describe the neuro-vascular structures at risk for the most usual anterior and posterior approaches and provide strategies for prevention and treatment of these injuries.

Gargiulo Monachelli G, Meyer M, Rodriguez GE, Garay LI, Sica REP, De Nicola AF, Gonzalez Deniselle MC. Endogenous progesterone is associated to amyotrophic lateral sclerosis prognostic factors. Acta Neurol Scand: 2011: 123: 60–67. © 2010 John Wiley & Sons A/S. Negative prognostic factors in amyotrophic lateral sclerosis include advanced age, shorter time from disease onset to diagnosis, bulbar onset and rapid progression rate. Objective – To compare progesterone (PROG) and cortisol serum levels in patients and controls and ascertain its relationship to prognostic factors and survival. Methods – We assessed serum hormonal levels in 27 patients and 21 controls. Results – Both hormones were 1.4-fold higher in patients. PROG showed a negative correlation with age, positive correlation with survival and positive trend with time to diagnosis. Increased PROG was observed in spinal onset and slow progression patients. No correlation was demonstrated with cortisol. Conclusion – Increased hormonal levels in patients are probably due to hypothalamic–pituitary–adrenal axis activation. Nevertheless, in this preliminary report only PROG correlated positively with factors predicting better prognosis and survival. We hypothesize endogenous PROG and cortisol may be engaged in differential roles, the former possibly involved in a neuroprotective response.

Column experiments were conducted to investigate the transport and deposition behavior of representative hydrophobic and hydrophilic bacteria strains in sand at different water saturations. These strains are similar in surface charge, shape, and size, and differ primarily in their surface hydrophobicity and tendency to form aggregates. The amount of bacteria that were retained in the sand increased with decreasing water saturation, especially for the more hydrophobic strain that formed larger cell aggregates. Most of the cells were retained close to the column inlet, and the rate of deposition rapidly decreased with depth. The experimental data were analyzed using a mathematical model that accounted for deposition on two kinetic sites. Consideration of depth-dependent deposition in the model formulation significantly improved the description of the data, and the amount of cell retention was typically dominated by this site. The depth-dependent deposition coefficient tended to increase with decreasing water content, especially for the hydrophobic bacteria. Straining is believed to account for these observations because it increases in magnitude with increasing cell and aggregate size and when a greater fraction of the water flows through a larger number of small pore spaces with decreasing water content. Cell retention on the other kinetic deposition site was well described using a conventional model for attachment and detachment. Consistent with interaction energy calculations for bacteria attachment, however, low amounts of cell retention occurred on this site. Attempts to separately determine the amounts of attachment to solid–water and air–water interfaces were confounded by the influence of straining.

Bioremediation is a cost-efficient cleanup technique that involves the use of metabolically active bacteria to degrade recalcitrant pollutants. To further develop this technique it is important to understand the migration and deposition behavior of metabolically active bacteria in unsaturated soils. Unsaturated transport experiments were therefore performed using Deinococcus radiodurans cells that were harvested during the log phase and continuously supplied with nutrients during the experiments. Additional experiments were conducted using this bacterium in the stationary phase. Different water saturations were considered in these studies, namely 100 (only stationary phase), 80, and 40%. Results from this study clearly indicated thatthe physiological state of the bacteria influenced its transport and deposition in sands. Metabolically active bacteria were more hydrophobic and exhibited greater deposition than bacteria in the stationary phase, especially at a water saturation of 40%. The breakthrough curves for active bacteria also had low concentration tailing as a result of cell growth of retained bacteria that were released into the liquid phase. Collected breakthrough curves and deposition profiles were described using a model that simultaneously considers both chemical attachment and physical straining. New concepts and hypotheses were formulated in this model to include biological aspects associated with bacteria growth inside the porous media.

The occurrence and localization of neurotrophins and their specific TrK receptor-like proteins in the adrenal gland of chicken, duck and ostrich were examined by immunohistochemical methods. In all species studied NGF-, TrK A- and TrK C-like immunoreactivity was observed in neurons and fibers of adrenal ganglia. Thin TrK A- and TrK C-like immunoreactive fibers were also observed among chromaffin cells. NT-3-like immunoreactivity was detected in chromaffin cells as revealed by the double immunolabelings NT-3/chromogranin A and NT-3/DbetaH. The interrenal tissue never showed IR to any neurotrophins and TrK tested, and none of the adrenal structures displayed immunoreactivity to BDNF and TrK B. Double immunolabelings NGF/TrK A, NGF/TrK C and TrK A/TrK C showed colocalization in some neurons and fibers in adrenal ganglia. In adrenal glands of the species studied, the distribution of neurotrophins and TrK receptors could suggest an involvement of NT-3 on neuronal populations innervating adrenal ganglia by means of its high affinity receptor TrK C and low affinity receptor TrK A. In addition, NGF could be utilized by neuronal populations of adrenal ganglia through its preferential receptor TrK A by an autocrine or paracrine modality of action.

We study the asymptotic behavior of solutions of minimization problems of integral functionals with integrands satisfying p-growth conditions, with respect to constraints that are imposed on gradients of admissible functions on a periodic disperse set and with respect to periodic measures that are assumed to be nondegenerate and satisfying the Poincar´e inequality.

An aging population has lead to increased demand for health-care and an interest in moving health care services from the hospital to the home to reduce the burden on society. One enabling technology is comfortable monitoring and sensing of bio-signals. Sensors can be embedded in objects that people interact with daily such as a computer, chair, bed, toilet, car, telephone or any portable personal electronic device. Moreover, the relatively recent and wide availability of microelectronics that provide the capabilities of embedded software, open access wireless protocols and long battery life has led many research groups to develop wearable, wireless bio-sensor systems that are worn on the body and integrated into clothing. These systems are capable of interaction with other devices that are nowadays commonly in our possession such as a mobile phone, laptop, PDA or smart multifunctional MP3 player. The development of systems for wireless bio-medical long term monitoring is leading to personal monitoring, not just for medical reasons, but also for enhancing personal awareness and monitoring self-performance, as with sports-monitoring for athletes. These developments also provide a foundation for the Brain Computer Interface (BCI) that aims to directly monitor brain signals in order to control or manipulate external objects. This provides a new communication channel to the brain that does not require activation of muscles and nerves. This innovative and exciting research field is in need of reliable and easy to use long term recording systems (EEG). In particular we highlight the development and broad applications of our own circuits for wearable bio-potential sensor systems enabled by the use of an amplifier circuit with sufficiently high impedance to allow the use of passive dry electrodes which overcome the significant barrier of gel based contacts.

Satellite navigation technologies are the major technological enabler for improving safety and efficiency of vehicles mobility in urban and suburban areas. The potential to reduce the cost and the air pollution caused by traffic jams, to decrease the trip duration, to better exploit the existing road infrastructures, to provide faster and automated relief in case of accidents, to increase the vehicle active safety adapting to the road and environmental conditions, are only some examples of the benefits that the integration of satellite navigation technologies can provide to the road sector. In this frame the Italian Space Agency (ASI) launched in December 2008 the INFOSAT. The main objective of the INFOSAT Project is to design, develop at prototype level and demonstrate on the field, an integrated system based on navigation technologies and devoted to the following application areas: (a) electronic toll collection and accesses control, (b) traffic monitoring and control and (c) prevention, assistance and relief in emergency situations. INFOSAT project foresees different critical products useful for vehicular application: ELL critical product develops a differential correction computation algorithm, ALIVE and EIV algorithms aim to generate integrity information to be used for Emergency situation and toll collection and accesses control, iMAP that aims to integrate a map-matching algorithm with integrity information.

[Abriged] Astronomical Wide Field Imaging performed with new large format CCD detectors poses data reduction problems of unprecedented scale which are difficult to deal with traditional interactive tools. We present here NExt (Neural Extractor): a new Neural Network (NN) based package capable to detect objects and to perform both deblending and star/galaxy classification in an automatic way. Traditionally, in astronomical images, objects are first discriminated from the noisy background by searching for sets of connected pixels having brightnesses above a given threshold and then they are classified as stars or as galaxies through diagnostic diagrams having variables choosen accordingly to the astronomer's taste and experience. In the extraction step, assuming that images are well sampled, NExt requires only the simplest a priori definition of "what an object is" (id est, it keeps all structures composed by more than one pixels) and performs the detection via an unsupervised NN approaching detection as a clustering problem which has been thoroughly studied in the artificial intelligence literature. In order to obtain an objective and reliable classification, instead of using an arbitrarily defined set of features, we use a NN to select the most significant features among the large number of measured ones, and then we use their selected features to perform the classification task. In order to optimise the performances of the system we implemented and tested several different models of NN. The comparison of the NExt performances with those of the best detection and classification package known to the authors (SExtractor) shows that NExt is at least as effective as the best traditional packages.

Vibration treatment by oscillating platforms is more and more employed in the fields of exercise physiology and bone research. The rationale of this treatment is based on the neuromuscular system response elicited by vibration loads. surface Electromyography (EMG) is largely utilized to assess muscular response elicited by vibrations and Root Mean Square of the electromyography signals is often used as a concise quantitative index of muscle activity; in general, EMG envelope or RMS is expected to increase during vibration. However, it is well known that during surface bio-potential recording, motion artifacts may arise from relative motion between electrodes and skin and between skin layers. Also the only skin stretch, modifying the internal charge distribution, results in a variation of electrode potential. The aim of this study is to highlight the movements of muscles, and the succeeding relevance of motion artifacts on electrodes, in subjects undergoing vibration treatments. EMGs from quadriceps of fifteen subjects were recorded during vibration at different frequencies (15-40 Hz); Triaxial accelerometers were placed onto quadriceps, as close as possible to muscle belly, to monitor motion. The computed muscle belly displacements showed a peculiar behavior reflecting the mechanical properties of the structures involved. Motion artifact related to the impressed vibration have been recognized and related to movement of the soft tissues. In fact large artifacts are visible on EMGs and patellar electrodes recordings during vibration. Signals spectra also revealed sharp peaks corresponding to vibration frequency and its harmonics, in accordance with accelerometers data. © 2008 Springer-Verlag.

The presence and distribution of S100-like protein in the goldfish (Carassius auratus L.) kidney has been studied by the use of immunohistochemical and histochemical methods. Simple immunohistochemistry (peroxidase anti-peroxidase method) was carried out with a polyclonal antibody against a mixture of both S100α and S100β proteins. In order to confirm the cell-type containing S-100-like immunoreactivity, the colocalization of S-100-like protein immunoreactivity with periodic acid-Schiff (PAS) reaction was investigated by using double staining with indirect immunofluorescence and PAS histochemistry. S100-like immunoreactivity was detected only in juxtaglomerular cells located in the renal arterial branch and never on afferent arterioles. No immunoreactivity was observed in other tracts of the nephron or in the interstitial cells. Double staining confirmed that S-100-like immunoreactivity and PAS reactivity were colocalized in juxtaglomerular cells. These findings are the first regarding the presence and distribution of S100-like protein in the teleost kidney; they add a new member to the list of extra-neural S100-like-containing cell types and confirm that the antigen cannot be regarded as nervous-system-specific. In addition, a concentration of S100-like immunoreactivity in juxtaglomerular cells suggests the presence of S100-like calcium-binding protein-mediated activities in these cell types.

Neurotrophins are involved in the development and maintenance of some neuronal populations, acting through tyrosine protein kinase (Trk) receptors, TrkA, TrkB and TrkC. In addition, recent studies have demonstrated the occurrence of Trk receptors in a wide variety of adult and embryonic non-neuronal tissues in vertebrates, including kidney. Nevertheless no data are available on Trk proteins distribution in teleost kidney. The present study, by using an immunoperoxidase technique, analyses Trk receptor protein distribution in the kidney of three species of freshwater and saltwater teleost. TrkA-like immunoreactivity was the only one detected in all examined species, while TrkB-like immunoreactivity was completely absent and TrkC-like immunoreactivity was detected only in goldfish. The TrkA immunoreactive cells were mainly localised in the collecting duct system, as this system was the only one to also display TrkC. Such data could provide new clues to Trk in fish and aid assessment of the role of Trk protein receptors during vertebrate evolution.

In this paper a hybrid system and a hierarchical neural-net approaches are proposed to solve the automatic labeling problem for unsupervised clustering. The first method involves the application of nonneural clustering algorithms directly to the output of a neural net; and the second one is based on a multilayer organization of neural units. Both methods are a substantial improvement with respect to the most important unsupervised neural algorithms existing in the literature. Experimental results are shown to illustrate clustering performance of the systems.

Atrial fibrillation is an arrhythmia with high prevalence in the elderly and it is frequently associated with comorbidities and anatomical and functional cardiac abnormalities, such as reduced ventricular distensibility. In elderly patients, this arrhythmia is often associated with specific clinical conditions such as cognitive impairment and/or dementia. The pathophysiological mechanism underlying this relationship is unknown, although some evidences support the hypothesis of microthromboembolism and/or cerebral hypoperfusion due to reduced cardiac output. If not properly managed, atrial fibrillation determines a significant impact in terms of morbidity and mortality, especially in the elderly. To ensure the best result in terms of outcome, the management of atrial fibrillation should be individualized according to patient characteristics and the underlying conditions, which are critical in the elderly. The potential risk of bleeding of anti-coagulant and the side effects of antiarrhythmic drugs should not be overlooked. The new oral anticoagulants can potentially meet this need by ensuring greater efficiency, reduction of cardiovascular morbidity and mortality, and improved safety profile, especially in old age. Finally, the refinement of ablation techniques for the treatment of atrial fibrillation will certainly find a great impact in old age.

Histochemical changes of oxidative enzymes and cadmium uptake in the Carassius auratus gills were examined up to 7 days after a 87.6 μM cadmium exposure in very alkaline water in the presence and absence of catabolic ammonia. In the presence of catabolic NH3, the toxic action of cadmium is much more intense and determines a 20% survival of goldfish with a heavy increase in the excretion of mucus. Animals treated with cadmium only and controls survived in the order of 100%. More drastic histochemical alterations in the activity of oxidative enzymes (SDH, G-6-PDH, LDH) were documented in animals treated both with cadmium and ammonia, if compared with those treated with cadmium only. A reduction in the activity of enzymes after 24 h, a heavy increase of the LDH reaction after 72 h, and a strong increase after 7 days in the number of positive SDH cells (which correspond to chloride cells) were documented. After a hyperaccumulation at 24 h (returning afterwards to much lower values), at 7 days the cadmium uptake was higher in the animals treated both with cadmium and ammonia.

Treatment of chronic heart failure (CHF) is strongly focused on evidence-based medicine. However, large trials are often far away from the “real world” of geriatric patients and their messages are poorly transferable to the clinical management of CHF elderly patients. Precipitating factors and especially non-cardiac comorbility may decompensate CHF in the elderly. More importantly, drugs of first choice, such as Angiotensin Converting Enzyme inhibitors and β-blockers, are still underused and effective drugs on diastolic dysfunction are not available. Poor adherence to therapy, especially due to cognitive disorders and depression, worsens the management. Electrical therapy is indicated, but attention to the older age groups with reduced life expectancy has to be paid. Physical exercise, stem cells, gene therapy and new devices are encouraging, but definitive results are not available yet. Palliative care plays a key role in the end-stage of the disease. Follow-up of CHF elderly patient is very important but tele-medicine is the future. Finally, self-care management, caregiver training and multidimensional team represent the critical point of the treatment of CHF elderly patients.

Summary The influence of cadmium on Carassius auratus gut. The paper deals with the cadmium effects on the intestinal mucosa of adult Carassius auratus after 7, 14 and 40 days of exposure. After 7 days the mucosa becomes oedematous; the mucous cells show intensive secretion. The cells showing immunoreactivity for the Met- and Leuenkephaline miss this feature. After 14 days these modifications diminish and after 40 days disappear completely and the mucosa gains its normal characteristics. Resume Cette etude a permis d'examiner Taction du cadmium sur la muqueuse intestinale d'exemplaires adultes de Carassius auratus, exposes pendant 7, 14 et 40 jours au cadmium. Apres 7 jours, on a pu mettre en evidence des modifications au niveau de la muqueuse qui devient oedemateuse, au niveau des cellules mucipares qui entrent dans une intense phase secretaire et au niveau des cellules a reaction positive vis- a -vis de la Met- et de la Leu-encephaline, qui perdent cette positiviste. Ces modifications regressent a 14 jours et s'annulent completement apres 40 jours; la muqueuse retrouve alors son aspect et ses caracteristiques normales.

Leptin is a modulator of food intake and energy homeostasis both in mammals and in some species of nonmammals vertebrates. In this study, we reported for the first time, using an immunohistochemical and immunochemical approach, the presence and distribution of immunoreactivity to leptin-like protein in the gastroenteric tract of Dicentrarchus labrax (bass) and Carassius auratus (goldfish), two teleostean species with different feeding and different adaptative morphological organization of the gastroenteric tract. Bass stomach showed intense immunoreactivity to leptin-like protein in all regions, with immunoreactive cells located at the base of the mucosal plicae and at the apical margin of the gastric crypts. Immunoreactive fibers and neuronal cells were observed close to vascular structures in the pyloric region. In bass and goldfish intestine, rare immunoreactive cells were observed along the mucosal epithelium mostly at the base or the apex of intestinal folds in the proximal and medium intestine; numerous immunoreactive nerve fibers in the circular and longitudinal layers of the tunica muscolaris as well as in the myenteric plexus were observed. Western blot analysis recognized a ∼15 kDa signal with a similar expression pattern for goldfish and sea bass. Our results could contribute to confirm the evolutive conservation of leptin-like proteins and their probably precocious functional diversification in fish. Microsc. Res. Tech., 2011. © 2010 Wiley-Liss, Inc.

Summary This study evaluates cytokines production in bone and bone marrow of patients with an osteoporotic fracture or with osteoarthritis by real time PCR, Western blot and immunohistochemistry. We demonstrate that the cytokine pattern is shifted towards osteoclast activation and osteoblast inhibition in patients with osteoporotic fractures. Introduction Fragility fractures are the resultant of low bone mass and poor bone architecture typical of osteoporosis. Cytokines involved in the control of bone cell maturation and function are produced by both bone itself and bone marrow cells, but the roles of these two sources in its control and the amounts they produce are not clear. This study compares their production in patients with an osteoporotic fracture and those with osteoarthritis. Methods We evaluated 52 femoral heads from women subjected to hip-joint replacement surgery for femoral neck fractures due to low-energy trauma (37), or for osteoarthritis (15). Total RNA was extracted from both bone and bone marrow, and quantitative PCR was used to identify the receptor activator of nuclear factor kB Ligand (RANKL), osteoprotegerin (OPG), macrophagecolony stimulatingfactor (M-CSF), transforming growth factor β (TGFβ), Dickoppf-1 (DKK-1) and sclerostin (SOST) expression. Immunohisto- chemistry and Western blot were performed in order to quantify and localize in bone and bone marrow the cytokines. Results We found an increase of RANKL/OPG ratio, M- CSF, SOST and DKK-1 in fractured patients, whereas TGFβ was increased in osteoarthritic bone. Bone marrow produced greater amounts of RANKL, M-CSF and TGFβ compared to bone, whereas the production of DKK-1 and SOST was higher in bone. Conclusions We show that bone marrow cells produced the greater amount of pro-osteoclastogenic cytokines, whereas bone cells produced higher amount of osteoblast inhibitors in patients with fragility fracture, thus the cytokine pattern is shifted towards osteoclast activation and osteoblast inhibition in these patients.

The distribution of VIP-immunoreactive neurons and fibers was detected in the hypothalamus of the chick by immunohistochemistry and light microscopy. A large amount of VIP cellular bodies was localized in the anterior and medial area of the hypothalamus with the highest density of cells in supraoptic, magnocellular preoptic, suprachiasmatic and paraventricular nuclei. Only few VIP-immunoreactive neurons were observed in the caudal section of infundibuli nucleus. A considerable concentration of VIP-positive fibers was also detected in the external layer of the anterior and posterior median eminence. Their presence might have origin both from the neurons of the infundibuli nucleus and from the cells of the paraventricular nucleus. Few VIP-immunoreactive fibers were revealed in the organum vasculosum of the lamina terminalis. These results tend to suggest that VIP may play more than one role in the hypothalamic regions, particularly in the preoptico-hypothalamic area. The presence of this peptide in the median eminence supports even more the hypothesis that it may be released into the portal circulation and transported to the pars distalis of the pituitary gland.

1. Uptake of cadmium and histochemical changes of mucopolysaccharides and of cytochromeoxidase in the gill epithelium of Carassius auratus were examined at different times after 10ppm Cd 2+ exposure in hard water (520 mg/l CaCO 3 ). 2. All animals survived treatment and no significant behavioural changes were observed. 3. Cd 2+ precipitates completely as CdCO 3 in the first 72 hr. Nevertheless, metal uptake in the organ was observed beyond this period. 4. After 96 hr an increase in the amount of sulphate mucins and a reduction in intensity of the cytochrome-oxidase reaction were observed. 5. Cadmium toxicity in very hard water is interpreted as being due to CdCO 3 ingestion which might cause histochemical alterations in the gills.

Non-specific and tuberculous infections of the cervical spine are a rare disease in developed countries. In 1962-1988 in the Orhopaedic Institute Rizzoli 32 patients with spondylitis of the cervical spine were treated. Twenty-nine patients came from Italy and three from Africa. Tuberculous infection was present in 23 patients, non-specific infection in nine. Eight tuberculous infections were in the atlanto-axial junction, the remaining ones at lower levels. The diagnosis was assessed by clinical and X-ray methods, only in four instances it was verified by histological examination. Conservative treatment was provided in 26 patients and surgery in five. In the nine non-specific infections orthopaedic and antibiotic treatment was successful, three patients were operated, their case-histories are presented. All cases of tuberculous inflammations were treated conservatively by immobilization and antituberculous treatment. Only in two surgery was called for due to instability of the spine. Both case-histories are presented. Based on the assembled results, the authors recommend in the discussion indications for and the procedure of conservative treatment and in exceptional cases surgical treatment of infections affecting the cervical spine. Key words: infection of the cervical spine, conservative and surgical treatment.

1. 1. Behavioural activities and histochemical changes of mucopolysaccharides, ATPase and respiratory enzymes in the gill epithelium of freshwater fish Poecilia reticulata Peters were examined at different times after 100% sea-water exposure. 2. 2. Acute stress was observed in the first 6 hr, with behavioural and histochemical changes. 3. 3. Up to 6 hr reduction in reaction activities of succinic-dehydrogenase, cytochrome-oxidase, ATPase and mucopolysaccharides was observed. 4. 4. After the first 6 hr a strong increase in ATPase and respiratory enzymes levels was observed until they reached levels similar to the controls at 7 days. Mueopolysaccharide reactions were gradually reduced and disappeared completely at 7 days. 5. 5. Behavioural adaptations changed in the same time and behavioural activity appeared normal at 24 hr. 6. 6. A correlation between the adaptive flexibility of P. reticulata and morphological and physiological characters is hypothesized.