Extracellular calcium antagonizes forskolin-induced aquaporin 2 trafficking in collecting duct cells

BACKGROUND: Urinary concentrating defects and polyuria are the most important renal manifestations of hypercalcemia and the resulting hypercalciuria. In this study, we tested the hypothesis that hypercalciuria-associated polyuria in kidney collecting duct occurs through an impairment of the vasopressin-dependent aquaporin 2 (AQP2) water channel targeting to the apical membrane possibly involving calcium-sensing receptor (CaR) signaling. METHODS: AQP2-transfected collecting duct CD8 cells were used as experimental model. Quantitation of cell surface AQP2 immunoreactivity was performed using an antibody recognizing the extracellular AQP2 C loop. Intracellular cyclic adenosine monophosphate (cAMP) accumulation was measured in CD8 cells using a cAMP enzyme immunoassay kit. To study the translocation of protein kinase C (PKC), membranes or cytosol fractions from CD8 cells were subjected to Western blotting using anti-PKC isozymes antibodies. The amount of F-actin was determined by spectrofluorometric techniques. Intracellular calcium measurements were performed by spectrofluorometric analysis with Fura-2/AM. RESULTS: We demonstrated that extracellular calcium (Ca2+ o) (5 mmol/L) strongly inhibited forskolin-stimulated increase in AQP2 expression in the apical plasma membrane. At least three intracellular pathways activated by extracellular calcium were found to contribute to this effect. Firstly, the increase in cAMP levels in response to forskolin stimulation was drastically reduced in cells pretreated with Ca2+ o compared to untreated cells. Second, Ca2+ o activated PKC, known to counteract vasopressin response. Third, quantification of F-actin demonstrated that Ca2+ o caused a nearly twofold increase in F-actin content compared with basal conditions. All these effects were mimicked by a nonmembrane permeable agonist of the extracellular CaR, Gd3+. CONCLUSION: Together, these data demonstrate that extracellular calcium, possibly acting through the endogenous CaR, antagonizes forskolin-induced AQP2 translocation to the apical plasma membrane in CD8 cells. In hypercalciuria, this mechanism might blunt water reabsorption and prevent further calcium concentration, thus protecting against a potential risk of urinary calcium-containing stone formation

Deficits in prospective memory following damage to the medial subdivision of the mediodorsal thalamic nucleus.

Identifying the neurocognitive mechanisms that lead individuals remembering to execute an intention at the right moment (prospective memory, PM) and how such mechanisms are influenced by the features of that intention is a fundamental theoretical challenge. In particular, the functional contribution of subcortical regions to PM is still unknown. This study was aimed at investigating the role of the medial subdivision of the mediodorsal thalamic nucleus (mMDT) in PM, with particular focus on the processes that are mediated by the projections from/to this structure. We analyzed the performance of a patient (OG) with a right-sided lesion involving the mMDT in a series of PM tasks that varied for focality (i.e., overlapping of processes for the PM and ongoing tasks) and emotional valence of the stimuli, comparing the patient’s performance with that of a control group. We found that the mMDT damage led to deficits in PM that were modulated by focality and emotional valence. OG indeed showed: a greater cost in the ongoing performance when a nonfocal PM task was added; a slowing down in retrieving the intentions, in particular when these were associated with focal PM cues; an abnormal performance in the task with positive PM cues. Our findings provide evidence of a contribution of mMDT to PM and suggest a modulation of prefrontal-dependent strategic monitoring and a possible interaction with the limbic structures in the integration of emotion and PM processes. They also give support to the still controversial idea that connections with the perirhinal cortex mediate familiarity-based recognition

Photo-oxidation of ethylene over mesoporous Tio2/Sio2 catalysts

Mesoporous TiO2/SiO2 catalysts were prepared in order to increase the post-harvest life of climacteric fruits and vegetables reducing ethylene concentration by photo-oxidation. TiO2/SiO2 powders were synthesized by sol-gel method using titanium isopropoxide Ti(OiPr)4 and tetraethoxysilane Si(OC2H5)4 as source of metal oxides. Mesoporous SiO2 framework was used as catalyst support of nanostructured TiO2 to enhance the photocatalytic efficiency. Different TiO2/SiO2 molar ratios were prepared through sol-gel process. A liquid-crystal template route allowed to obtain the mesoporous silica structure, and contemporary TiO2 insertion in the silica framework. The X-ray diffraction (XRD) analysis demonstrated that silica insertion in TiO2 framework inhibits the anatase to rutile phase transformation at higher sintering temperature. The photocatalytic efficiency of the catalysts was measured by the photo-oxidation of ethylene gas under UV light irradiation. Complete photo-oxidation of ethylene was observed after 24 h of reaction time. Results show that the silica framework increases the surface area of the composites and make crystalline anatase phase more stable at higher temperature

Applying spatial reasoning to topographical data with a grounded geographical ontology

Grounding an ontology upon geographical data has been pro- posed as a method of handling the vagueness in the domain more effectively. In order to do this, we require methods of reasoning about the spatial relations between the regions within the data. This stage can be computationally expensive, as we require information on the location of points in relation to each other. This paper illustrates how using knowledge about regions allows us to reduce the computation required in an efficient and easy to understand manner. Further, we show how this system can be implemented in co-ordination with segmented data to reason abou

The Relationship between Life Course Socioeconomic Conditions and Objective and Subjective Memory in Older Age.

While objective memory performance in older adults was primarily shown to be affected by education as indicator of life course socioeconomic conditions, other life course socioeconomic conditions seem to relate to subjective memory complaints. However, studies differ in which life course stages were investigated. Moreover, studies have explored these effects in an isolated way, but have not yet investigated their unique effect when considering several stages of the life course simultaneously. This study, therefore, examined the respective influence of socioeconomic conditions from childhood up to late-life on prospective memory (PM) performance as an objective indicator of everyday memory as well as on subjective memory complaints (SMC) in older age using structural equation modeling. Data came from two waves of the Vivre-Leben-Vivere aging study (n=993, Mage=80.56). The results indicate that only socioeconomic conditions in adulthood significantly predicted late-life PM performance. PM performance was also predicted by age and self-rated health. In contrast, SMC in older age were not predicted by socioeconomic conditions at any stage of the life course but were predicted by level of depression. In line with the cognitive reserve hypothesis, present results highlight the significance of education and occupation (adulthood socioeconomic conditions) for cognitive functioning in later life

Screening for frailty in older patients with early-stage solid tumors: a prospective longitudinal evaluation of three different geriatric tools

Advance Access publication February 2, 2017Background: Frailty increases the risk of adverse health outcomes and/or dying when exposed to a stressor, and routine frailty assessment is recommended to guide treatment decision. The Balducci frailty criteria (BFC) and Fried frailty criteria (FFC) are commonly used, but these are time consuming. Vulnerable Elders Survey-13 (VES-13) score of ≥7, a simple and resource conserving function-based scoring system, may be used instead. This prospective study evaluates the performance of VES-13 in parallel with BFC and FFC, to identify frailty in elderly patients with early-stage cancer. Methods: Patients aged ≥70 years with early-stage solid tumors were classified as frail/nonfrail based on BFC (≥1 criteria), FFC (≥3 criteria), and VES-13 (score ≥ 7). All patients were assessed for functional decline and death. Results: We evaluated 185 patients. FFC had a 17% frailty rate, whereas BFC and VES-13 both had 25%, with poor concordance seen between the three geriatric tools. FFC (hazard ratio = 1.99, p = .003) and VES-13 (hazard ratio = 2.81, p < .001) strongly discriminated for functional decline, whereas BFC (hazard ratio = 3.29, p < .001) had the highest discriminatory rate for deaths. BFC and VES-13 remained prognostic for overall survival in multivariate analysis correcting for age, tumor type, stage, and systemic treatment. Conclusions: A VES-13 score of ≥7 is a valuable discriminating tool for predicting functional decline or death and can be used as a frailtyscreening tool among older cancer patients in centers with limited resources to conduct a comprehensive geriatric assessment.Laura Biganzoli, Anna Rachelle Mislang, Samantha Di Donato, Dimitri Becheri, Chiara Biagioni, Stefania Vitale, Giuseppina Sanna, Elena Zafarana, Stefano Gabellini, Francesca Del Monte, Elena Mori, Daniele Pozzessere, Antonella Brunello, Andrea Luciani, Letizia Laera, Luca Boni, Angelo Di Leo, and Giuseppe Mottin

Intracranial complications of sinogenic and otogenic infections in children:an ESPN survey on their occurrence in the pre-COVID and post-COVID era

Background: COVID-19 pandemic is thought to have changed the epidemiology of some pediatric neurosurgical disease: among them are the intracranial complications of sinusitis and otitis (ICSO). According to some studies on a limited number of cases, both streptococci-related sinusitis and ICSO would have increased immediately after the pandemic, although the reason is not clear yet (seasonal changes versus pandemic-related effects). The goal of the present survey of the European Society for Pediatric Neurosurgery (ESPN) was to collect a large number of cases from different European countries encompassing the pre-COVID (2017–2019), COVID (2020–2021), and post-COVID period (2022–June 2023) looking for possible epidemiological and/or clinical changes. Material and methods: An English language questionnaire was sent to ESPN members about year of the event, patient’s age and gender, presence of immune-deficit or other favoring risk factors, COVID infection, signs and symptoms at onset, site of primary infection, type of intracranial complication, identified germ, type and number of surgical operations, type and duration of medical treatment, clinical and radiological outcome, duration of the follow-up. Results: Two hundred fifty-four cases were collected by 30 centers coming from 14 different European countries. There was a statistically significant difference between the post-COVID period (129 children, 86 cases/year, 50.7% of the whole series) and the COVID (40 children, 20 cases/year, 15.7%) or the pre-COVID period (85 children, 28.3 cases/year, 33.5%). Other significant differences concerned the presence of predisposing factors/concurrent diseases (higher in the pre-COVID period) and previous COVID infection (higher in the post-COVID period). No relevant differences occurred as far as demographic, microbiological, clinical, radiological, outcome, morbidity, and mortality data were concerned. Paranasal sinuses and middle ear/mastoid were the most involved primary site of infection (71% and 27%, respectively), while extradural or subdural empyema and brain abscess were the most common ICSO (73% and 17%, respectively). Surgery was required in 95% of cases (neurosurgical and ENT procedure in 71% and 62% of cases, respectively) while antibiotics in 99% of cases. After a 12.4-month follow-up, a full clinical and radiological recovery was obtained in 85% and 84% of cases, respectively. The mortality rate was 2.7%. Conclusions: These results suggest that the occurrence of ICSO was significantly increased after the pandemic. Such an increase seems to be related to the indirect effects of the pandemic (e.g., immunity debt) rather than to a direct effect of COVID infection or to seasonal fluctuations. ICSO remain challenging diseases but the pandemic did not affect the management strategies nor their prognosis. The epidemiological change of sinusitis/otitis and ICSO should alert about the appropriate follow-up of children with sinusitis/otitis.</p