"Investigation on the role of Cl- homeostasis and GABAergic transmission in sleep disorders of Down syndrome and in Prader Willi syndrome: a possible contributor to cognitive impairment"

GABA is the main inhibitory neurotransmitter of the central nervous system (CNS). Recently, GABAergic transmission has been reported to be depolarizing and possibly excitatory rather than inhibitory in a number of neurodevelopmental disorders both in patients and mouse models. In particular, the Ts65Dn mouse model of Down syndrome (DS) exhibits depolarizing GABA due to upregulation of the Cl- importer NKCC1 both in the hippocampus and in the cortex. Moreover, NKCC1 inhibition by the FDA-approved diuretic bumetanide is able to rescue inhibitory GABAergic transmission, synaptic plasticity and cognitive functions in Ts65Dn mice. Beside cognitive impairment, DS mice and people with DS show sleep disturbaces. Since sleep pattern is regulated by GABAergc transmission, we reasoned that the alteration of GABAergic transmission due to upregulation of NKCC1 might be underlying at least some of the sleep disturbances in DS mice. So, we characterized sleep in Ts65Dn mice and investigated the effects of a chronic treatment with bumetanide. We found that bumetanide ameliorates the quality of sleep in NREM and REM sleep phases before and after sleep deprivation and decreases abnormal wakefulness during light phase at baseline in Ts65Dn mice. Moreover, we also found abnormalities in other parameters, which could contribute to sleep abnormalities of Ts65Dn mice: an increase of food intake and activity (partially rescued by bumetanide) with a reduction of body temperature during dark phase. Because of the association of altered GABAergic signaling by dysregulation of the expression of NKCC1 (but also of the Cl- exporter KCC2) in many neurodevelopmental disorders characterized by cognitive or social impairment, and sleep disorders, we extended our studies to Prader Willi syndrome (PWS). PWS is a neurodevelopmental disorder, caused by defects of genomic imprinting and characterized by cognitive, social and sleep abnormalities. Here, we observed that the Snord116 5 mutant mouse model of PWS, PWScrm+/p 12 show an increased expression of NKCC1, specifically in the hippocampus in comparison to their wild-type mice. Moreover, we report that PWS mice have altered cognition and the circadian period in free-running conditions. In particular, mutant mice present defects of long-term memory and a reduced shortening of their circadian period together with an increase of alpha activity in dark-dark (DD). Moreover, they also show alteration of pain sensitivity, that could be linked to defects in the thermoregulation. Interestingly, in constrast with PWS people, Snord116 mutant mice showed no alterations of anxiety, repetivive, obsessive and social behaviors. In an effort to rescue cognition and the circadian phenotype by rescuing NKCC1 inhibition, we treated Snord116 mutant mice with bumetanide. Remarkably, bumetanide treatment resulted in a complete rescue of the cognitive defects and circadian alteration in DD, with no effects in controls. Our results suggest an important link between GABA transmission and the regulation of cognition and the circadian clock in PWS. In addition, the current study extends the repertoire of disorders in which NKCC1 inhibition attenuates behavioural deficits and proposes a new potential mechanism for the investigation of PWS

Inherent Safety Development Applied to Green Processes and Energy Transition

Agri-food wastes are annually generated in huge amounts along the whole supply chain and are distinguished for their high moisture content, biological instability, organic load, and potential environmental impact, contributing to climate changes. For these reasons, agri-food waste reuse and recycle are highlighted by EU within a broader biorefinery concept. In this context, spent coffee grounds (SCGs) represent a promising source of high-added value compounds due to their appreciable amounts of polyphenols, caffeine, and lipids, which can be recovered to find applications in several industrial fields. Nevertheless, the unit operation of solid-liquid extraction, can be carried out by several alternative methods and solvents under different operating conditions. Green extraction processes can be seen as an alternative to conventional solvent extraction, but may entail new threats that require further investigation, since the equivalence between green and safer must not be taken for granted. Each option inevitably comprises several hazards, including fire and explosion to be “aprioristically” considered at the initial design stages. This work focuses on the implementation of specific inherent safety indexes to compare SCGs treatments alternatives for designing intrinsically safer plants and contributing to a more aware transition to green processes

Accuracy of Sentinel Lymph Node Mapping After Previous Hysterectomy in Patients with Occult Cervical Cancer.

BACKGROUND In patients with a diagnosis of occult cervical cancer made on a hysterectomy specimen after surgery for a benign indication, lymph node assessment is crucial to determine treatment. We aimed to compare sentinel lymph node (SLN) mapping between patients with postoperative diagnosis of occult cervical carcinoma and patients with cervical cancer and uterus in situ. METHODS A retrospective analysis of cervical cancer patients International Federation of Gynecology and Obstetrics (FIGO) stage IA-IIA disease undergoing laparoscopic SLN mapping was performed. Patients were divided into two groups: those with a diagnosis of occult cervical cancer made on a hysterectomy specimen (group 1) and those with a diagnosis of cervical cancer and uterus in situ (group 2). Tracers used for SLN mapping included technetium-99m ((99m)Tc), blue dye, and indocyanine green. After detection and excision, the SLN was sent for frozen section analysis, and the planned surgical procedure was aborted in case of metastatic disease in favor of a chemoradiotherapeutic treatment. RESULTS Groups 1 and 2 included 9 and 62 patients, respectively. Clinicopathologic characteristics were similar among the two groups. Overall and bilateral detection rates were 66.6 and 33.3 and 95.1 and 87 % in groups 1 and 2, respectively (p < 0.05). No false-negative SLNs were identified in either group, with a negative predictive value of 100 %. CONCLUSIONS SLN mapping in occult cervical cancer patients has lower detection rates compared to patients with uterus in situ. In these patients, proper management of their disease has already failed before diagnosis, and additional mistakes may definitely compromise attempts at cure

El alambrado eléctrico

EEA Valle InferiorFil: Bolla, Daniel Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Valle Inferior; ArgentinaFil: Kugler, Nora María. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Valle Inferior; Argentin

El negocio de la vaca de descarte. Análisis de una experiencia

EEA Valle InferiorFil: Barbarossa, Raúl Antonio. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Valle Inferior; ArgentinaFil: Garcilazo, María Gabriela. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Valle Inferior; ArgentinaFil: Bolla, Daniel Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Valle Inferior; Argentin

A Dynamic Approach to Natech Risk Assessment Applied to an LPG Storage Facility in a Landslides Sensitive Italian Area

Due to the climate change, extreme weather phenomena are becoming increasingly intense and occur with higher frequencies, even in unusual areas. Nevertheless, historical data showed as Natech accidents can be triggered not only by natural disasters, like earthquakes or tornadoes, but even by natural phenomena that are considered of minor importance, such as rain and lightning. Only recently, the Natech issue has gained a great deal of attention, but there is still a lack of consolidated Natech risk-analysis methodologies and tools. The focus of this work is to include natural hazards into a dynamic risk assessment system beside the typical parameters of process risks. In Italy, rainfall represents the most common triggering factor for landslides. Generally, the determination of trigger and propagation can rely on physically-based approaches, which require the calibration of many parameters and are often difficult to apply, or on empirical correlations between rainfall and landslide built from historical data. On the other hand, by using a data driven approach, available data can be exploited to define the system state over time, anticipate the systems outcome, support decision-making, and adopt the most appropriate adjustments, allowing to enhance system resilience and knowledge. The actual capability of the proposed approach was evaluated on a simple case-study represented by an LPG storage facility located in landslides sensitive zone of Liguria Region

Adecuación de la carga a la disponibilidad forrajera. Consideraciones para tener en cuenta

Tanto productores como técnicos y la sociedad en su conjunto han sufrido en el pasado los efectos negativos de la sequía, desde el punto de vista productivo, económico, social, ambiental y emocional. La ganadería fue especialmente afectada y sus impactos adversos se proyectaron en el corto, mediano y largo plazo.EEA Valle InferiorFil: Antenao, Juan Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Valle Inferior; ArgenitnaFil: Silva, Miguel Angel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Valle Inferior; ArgenitnaFil: Echevarria, Daniela. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Valle Inferior; ArgenitnaGarcilazo, María Gabriela. .Instituto de Tecnología Agropecuaria Estación Experimental Agropecuaria Valle Inferior.; ArgenitnaFil: Bolla, Daniel Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Valle Inferior; Argenitn

Impact of hormonal treatment duration in combination with radiotherapy for locally advanced prostate cancer: Meta-analysis of randomized trials

<p>Abstract</p> <p>Background</p> <p>Hormone therapy plus radiotherapy significantly decreases recurrences and mortality of patients affected by locally advanced prostate cancer. In order to determine if difference exists according to the hormonal treatment duration, a literature-based meta-analysis was performed.</p> <p>Methods</p> <p>Relative risks (RR) were derived through a random-effect model. Differences in primary (biochemical failure, BF; cancer-specific survival, CSS), and secondary outcomes (overall survival, OS; local or distant recurrence, LR/DM) were explored. Absolute differences (AD) and the number needed to treat (NNT) were calculated. Heterogeneity, a meta-regression for clinic-pathological predictors and a correlation test for surrogates were conducted.</p> <p>Results</p> <p>Five trials (3,424 patients) were included. Patient population ranged from 267 to 1,521 patients. The longer hormonal treatment significantly improves BF (with significant heterogeneity) with an absolute benefit of 10.1%, and a non significant trend in CSS. With regard to secondary end-points, the longer hormonal treatment significantly decrease both the LR and the DM with an absolute difference of 11.7% and 11.5%. Any significant difference in OS was observed. None of the three identified clinico-pathological predictors (median PSA, range 9.5-20.35, Gleason score 7-10, 27-55% patients/trial, and T3-4, 13-77% patients/trial), did significantly affect outcomes. At the meta-regression analysis a significant correlation between the overall treatment benefit in BF, CSS, OS, LR and DM, and the length of the treatment was found (p≤0.03).</p> <p>Conclusions</p> <p>Although with significant heterogeneity (reflecting different patient' risk stratifications), a longer hormonal treatment duration significantly decreases biochemical, local and distant recurrences, with a trend for longer cancer specific survival.</p