A protein kinase a-independent pathway controlling aquaporin 2 trafficking as a possible cause for the syndrome of inappropriate antidiuresis associated with polycystic kidney disease 1 haploinsufficiency.

Renal water reabsorption is controlled by vasopressin (AVP) which binds to V2 receptors resulting in PKA activation, phosphorylation of AQP2 at serine 256 (pS256) and translocation to the plasma membrane. Besides S256, AVP causes dephosphorylation of S261. Recent studies showed that cyclin-dependent kinases can phosphorylate S261 AQP2 peptides in vitro. In an attempt to investigate the possible role of cdks on AQP2 phosphorylation, we identified a new PKA-independent pathway regulating AQP2 trafficking. In ex-vivo kidney slices and MDCK-AQP2 cells, R-roscovitine, a specific cdks inhibitor, increased pS256 and decreased pS261. The changes in AQP2 phosphorylation were paralleled by an increase in cell surface AQP2 expression and osmotic water permeability in the absence of forskolin stimulation. Of note, R-roscovitine didn’t alter cAMP-dependent PKA activity. Because phosphorylation results from the balance between kinase and phosphatase activity, we evaluated the possible contribution of protein phosphatases PP1, PP2A and PP2B. Of these, R-roscovitine treatment specifically reduced PP2A protein expression and activity in MDCK cells. Interestingly, in PKD1+/- mice displaying a syndrome of inappropriate antidiuresis with high level of pS256 despite unchanged AVP and cAMP, we found a reduced PP2A expression and activity and reduced pS261. Similarly to what previously found in PKD1+/- mice, R-roscovitine treatment caused a significant decrease in intracellular calcium in MDCK cells. Our data indicate that a reduced activity of PP2A, secondary to reduced intracellular Ca2+ levels, promotes AQP2 trafficking independently of the AVP-PKA axis. This pathway may be relevant for explaining pathological states characterized by inappropriate AVP secretion and positive water balance

Interleukin-32 in systemic sclerosis, a potential new biomarker for pulmonary arterial hypertension

Background: Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis (SSc), associated with a progressive elevation in pulmonary vascular resistance and subsequent right heart failure and death. Due to unspecific symptoms, the diagnosis of PAH is often delayed. On this basis, it is of great value to improve current diagnostic methods and develop new strategies for evaluating patients with suspected PAH. Interleukin-32 (IL-32) is a proinflammatory cytokine expressed in damaged vascular cells, and the present study aimed to assess if this cytokine could be a new biomarker of PAH during SSc. Methods: The IL-32 expression was evaluated in the sera and skin samples of 18 SSc-PAH patients, 21 SSc patients without PAH, 15 patients with idiopathic PAH (iPAH) and 14 healthy controls (HCs), by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC). Receiver-operating characteristic (ROC) curves were performed to evaluate the cut-off of IL-32 in identifying patients with PAH. Furthermore, in SSc patients, correlation analyses were performed between IL-32 sera levels and mean pulmonary artery pressure (mPAP) evaluated by right heart catheterization (RHC) and systolic pulmonary artery pressure (sPAP), obtained by echocardiography. Additionally, the number of skin IL-32+ cells was correlated with modified Rodnan skin score (mRSS). Results: In SSc-PAH patients, IL-32 sera levels were significantly higher when compared with SSc patients without PAH and patients affected by iPAH. The analysis of ROC curve showed that IL-32 sera levels above 11.12 pg/ml were able to predict patients with PAH (sensitivity = 90%, specificity = 100%). Furthermore, the IL-32 sera levels of patients with SSc correlated with both mPAP and sPAP. In the skin derived from SSc-PAH patients, the number of IL-32+ cells was significantly increased when compared with the skin derived from SSc patients without PAH, correlating with the mRSS. Conclusion: Our study suggested that sera determination of IL-32 may be a promising approach to evaluate the presence of PAH in SSc patients and together with longitudinal future studies could help to increase the understanding how these biomarkers mirror the vascular changes and the inflammatory process during SSc

Connectome dysfunction in patients at clinical high risk for psychosis and modulation by oxytocin

Abnormalities in functional brain networks (functional connectome) are increasingly implicated in people at Clinical High Risk for Psychosis (CHR-P). Intranasal oxytocin, a potential novel treatment for the CHR-P state, modulates network topology in healthy individuals. However, its connectomic effects in people at CHR-P remain unknown. Forty-seven men (30 CHR-P and 17 healthy controls) received acute challenges of both intranasal oxytocin 40 IU and placebo in two parallel randomised, double-blind, placebo-controlled cross-over studies which had similar but not identical designs. Multi-echo resting-state fMRI data was acquired at approximately 1 h post-dosing. Using a graph theoretical approach, the effects of group (CHR-P vs healthy control), treatment (oxytocin vs placebo) and respective interactions were tested on graph metrics describing the topology of the functional connectome. Group effects were observed in 12 regions (all p  < 0.05) most localised to the frontoparietal network. Treatment effects were found in 7 regions (all p  < 0.05) predominantly within the ventral attention network. Our major finding was that many effects of oxytocin on network topology differ across CHR-P and healthy individuals, with significant interaction effects observed in numerous subcortical regions strongly implicated in psychosis onset, such as the thalamus, pallidum and nucleus accumbens, and cortical regions which localised primarily to the default mode network (12 regions, all p  < 0.05). Collectively, our findings provide new insights on aberrant functional brain network organisation associated with psychosis risk and demonstrate, for the first time, that oxytocin modulates network topology in brain regions implicated in the pathophysiology of psychosis in a clinical status (CHR-P vs healthy control) specific manner. [Abstract copyright: © 2024. The Author(s).

Seismological constraints for the dyke emplacement of the July-August 2001 lateral eruption at Mt. Etna volcano, Italy

In this paper we report seismological evidence regarding the emplacement of the dike that fed the July 18 - August 9, 2001 lateral eruption at Mt. Etna volcano. The shallow intrusion and the opening of the eruptive fracture system, which mostly occurred during July 12, and July 18, were accompanied by one of the most intense seismic swarms of the last 20 years. A total of 2694 earthquakes (1 £ Md £ 3.9) were recorded from the beginning of the swarm (July 12) to the end of the eruption (August 9). Seismicity shows the upward migration of the dike from the basement to the relatively thin volcanic pile. A clear hypocentral migration was observed, well constraining the upwards propagation of a near-vertical dike, oriented roughly N-S, and located a few kilometers south of the summit region. Earthquake distribution and orientation of the P-axes from focal mechanisms indicate that the swarm was caused by the local stress source related to the dike intrusion

Quantifying probabilities of eruption at a well-monitored active volcano: an application to Mount Etna (Sicily, Italy).

At active volcanoes, distinct eruptions are preceded by complex and different precursory patterns; in addition, there are precursory signals which do not necessarily lead to an eruption. The main purpose of this paper is to present an unprecedented application of the recently developed code named BET_EF (Bayesian Event Tree_Eruption Forecasting) to the quantitative estimate of the eruptive hazard at Mt. Etna volcano. We tested the model for the case history of the July-August 2001 flank eruption. Anomalies in geophysical, geochemical and volcanological monitoring parameters were observed more than a month in advance of the effective onset of the eruption. As a consequence, eruption probabilities larger than 90% were estimated. An important feature of the application of BET_EF to Mt. Etna was the probabilistic estimate of opening vent locations. The methodology allowed a clear identification of assumptions and monitoring parameter thresholds and provided rational means for their revision if new data or information are incoming

Pain, Parental Involvement, and Oxytocin in the Neonatal Intensive Care Unit

Preterm infants (PTI) typically experience many painful and stressful procedures or events during their first weeks of life in a neonatal intensive care unit, and these can profoundly impact subsequent brain development and function. Several protective interventions during this sensitive period stimulate the oxytocin system, reduce pain and stress, and improve brain development. This review provides an overview of the environmental risk factors experienced by PTI during hospitalization, with a focus on the effects of pain, and early maternal separation. We also describe the long-term adverse effects of the simultaneous experiences of pain and maternal separation, and the potential beneficial effects of maternal vocalizations, parental contact, and several related processes, which appear to be mediated by the oxytocin system

Ecological challenges for the buffer zone management of protected areas of forest-savannah mosaic in West Africa

In sub-Saharan Africa, the management of buffer zones around protected areas does not often take into serious account the needs of resource exploitation by the local populations or the conservation needs of these areas. We described the ecological characteristics and management issues affecting the buffer zone around the Fazao-Malfakassa National Park; a 192,000-ha protected area in central-western Togo of utmost conservation importance within the Dahomey Gap region. Within the buffer zone (10 km radius, 334,800 ha), we focussed on four high conservation value areas totalling 65,594 ha (20% of the total buffer zone area). Using 2015 sentinel-2 images we analyzed land cover patterns and described existing ecological zones. We complemented these with field surveys and interviews with 300 people living in 22 villages within the buffer zone to describe the conditions affecting the resident human population. Although over 60% of the total buffer zone area is degraded, we identified four areas of high conservation value (total area = 65,594 ha). Interviewees recognized that slash-and-burn was the most common form of land use, followed by agroforestry practices. Agriculture, charcoal, and firewood production were the main drivers affecting habitats, and land conflicts were recurrent due to the rise in human population. The decline in agriculture, reported by interviewees in some sectors, was attributable to ravages of crops by elephants. Three independent diversity indices showed that, in preserved zones, a greater diversity of animals (with similar utilization frequencies) were hunted than in degraded sites (where grasscutters were the dominant hunted species). There were also significant differences between degraded and preserved zones in terms of plants used for charcoal production and for non-timber forest products. We advocate the development of community-controlled hunting areas to enhance the conservation value of the four well-preserved zones. Instead, promoting sustainable agricultural production systems in the degraded areas can help to further stabilize the agricultural front and reduce land pressure on the park

Water safety in healthcare facilities. The Vieste Charter

The Study Group on Hospital Hygiene of the Italian Society of Hygiene, Preventive Medicine and Public Health (GISIO-SItI) and the Local Health Authority of Foggia, Apulia, Italy, after the National Convention "Safe water in healthcare facilities" held in Vieste-Pugnochiuso on 27-28 May 2016, present the "Vieste Charter", drawn up in collaboration with experts from the National Institute of Health and the Ministry of Health. This paper considers the risk factors that may affect the water safety in healthcare facilities and reports the current regulatory frameworks governing the management of installations and the quality of the water. The Authors promote a careful analysis of the risks that characterize the health facilities, for the control of which specific actions are recommended in various areas, including water safety plans; approval of treatments; healthcare facilities responsibility, installation and maintenance of facilities; multidisciplinary approach; education and research; regional and national coordination; communication