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European University alliances, formally introduced in 2019, are rapidly expanding, as more than 400 million euros have been dedicated in 2023 by the European Commission to foster international collaborations to promote new forms of development within and beyond university communities. By undertaking interventionist research on UNITA - Universitas Montium, one of the largest European alliances, representing 160.000 students, this paper aims to illustrate how a university alliance is tasked with developing an internal assessment methodology to account for the societal benefits created by the project for the academic and civil communities. The elaboration of the assessment tool to assess the contribution to higher education and societal sustainable communities has brought researchers to discover etic and emic implications, revealing the existence of an accountability layer in which the international alliance directly engages with rural and mountain communities in marginalized areas. This research marks a significant advancement in the field of higher education sustainability, providing both a novel analytical perspective on the benefits of university alliances for the development of local sustainable communities and a methodological tool for their assessment., (© 2024. The Author(s).)

Background/aims: In order to make the centers more attractive to trial sponsors, in recent years, some research institutions around the world have pursued projects to reorganize the pathway of trial activation, developing new organizational models to improve the activation process and reduce its times. This study aims at analyzing and reorganizing the start-up phase of trials conducted at the Research and Innovation Department (DAIRI) of the Public Hospital of Alessandria (Italy)., Methods: A project was carried out to reorganize the trial authorization process at DAIRI by involving the three facilities responsible for this pathway: clinical trial center (CTC), ethics committee secretariat (ESC), and administrative coordination (AC). Lean Thinking methodology was used with the A3 report tool, and the analysis was carried out by monitoring specific key performance indicators, derived from variables representing highlights of the trials' activation pathway. The project involved phases of analysis, implementation of identified countermeasures, and monitoring of timelines in eight 4-month periods. The overall mean and median values of studies activation times were calculated as well as the average times for each facility involved in the process., Results: In this study, 298 studies both sponsored by research associations and industry with both observational and interventional study design were monitored. The mean trial activation time was reduced from 218 days before the project to 56 days in the last period monitored. From the first to the last monitoring period, each facility involved achieved at least a halving of the average time required to carry out its activities in the clinical trials' activation pathway (CTC: 55 days vs 23, ECS: 25 days vs 8, AC 29 days vs 10). Average activation time for studies with agreement remains longer than those without agreement (100 days vs. 46)., Conclusions: The reorganization project emphasized the importance of having clinical and administrative staff specifically trained on the trial activation process. This reorganization led to the development of a standard operating procedure and a tool to monitor the time (KPIs of the process) that can also be implemented in other clinical centers., (© 2024. The Author(s).)

Anthocyanin and mechanical properties were evaluated on Shiraz grapes, picked from both sides of North-South and East-West vineyard row orientations at two harvest dates. Wines were made from each combination. The evaluation and evolution of crushed skin mechanical properties during maceration-fermentation, as also affected by grape ripeness, are shown for the first time. No significant differences in anthocyanin content were found in the grapes between the two vineyard row orientations. However, a significant decrease in anthocyanins and berry skin break force (also referred as skin hardness or strength) was found between the two harvest dates. During maceration, a reduction in the crushed berry skin break force of more than 15% occurred. The intact berries and macerated skins showed similarity in skin break energy values. The anthocyanin profile of the grapes and of the wines prominently displayed malvidin forms, changed mainly by the ripeness level of the grapes., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the impact of obesity in the safety of laparoscopic hysterectomy., Study Design: A retrospective study was conducted using a database of 2271 women undergoing laparoscopic hysterectomy for benign diseases between January 1995 and December 2008 at the Centre Hospitalier Universitaire Estaing (Clermont-Ferrand, France). Patients were divided into two groups according to the body mass index: <30 kg/m(2) (n=2088) and ≥ 30 kg/m(2) (n=183). Primary outcomes were differences in conversion rates, operating time, estimated blood loss, intraoperative complications, and early postoperative complications., Results: There was no difference in the operative time (121.3 versus 122.5 minutes; P=.71), in the difference between pre- and postoperative hemoglobin levels (1.8 versus 1.6 g/dL; P=.28), and in the conversion rate (4.6% versus 5.5%; P=.62) comparing the two groups. The overall intraoperative complication rate was 14.03% (n=293) and 13.66% (n=25) for nonobese and obese patients (P=.89), respectively. The overall postoperative complication rate was 8.81% (n=184) and 7.65% (n=14), respectively., Conclusions: Obesity does not have an adverse effect on the feasibility and safety of laparoscopic hysterectomy in experienced hands.

Objective: To evaluate the feasibility of laparoscopic hysterectomy for uteri weighing more than 1000 g., Study Design: A retrospective study was conducted in a tertiary center of laparoscopic surgery including 38 women submitted to hysterectomy for uteri weighing more than 1000 g. Patients submitted to open hysterectomy were compared to those submitted to laparoscopic hysterectomy. The primary statistical endpoint was the complication rate. Secondary endpoints were operating time, estimated blood loss, length of hospital stay, and conversion to laparotomy., Results: The patients' mean age was 49.4 years and mean BMI was 25.2 kg/m(2). The surgical intent was laparoscopic hysterectomy in 23 patients (60.5%) and laparotomy in 15 patients (39.5%). Conversion to open surgery was required in 4 patients (17.4%) due to inaccessibility of the pelvis at the beginning of surgery (n=2), technical difficulties during surgery (n=1), and intraoperative bleeding (n=1). One patient in the laparotomy group had an intraoperative ureteral injury. Despite longer operative time (130 vs. 80 min, p=0.002), laparoscopic surgery was associated with reduced length of hospital stay (3 vs. 6 days, p<0.001). Intraoperative bleeding was evaluated by the difference of pre- and post-operative hemoglobin and was equivalent in both groups (2.2 vs. 1.6g/dL; p=0.84). There was a tendency for more postoperative complications in the laparotomic group (33.4% vs. 8.7%; p=0.05)., Conclusion: Laparoscopic hysterectomy is feasible for selected patients with uteri weighing more than 1000 g., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Changes in the phenolic composition, phenol extractability indices, and mechanical properties occur in grape berries during the ripening process, but the heterogeneity of the grapes harvested at different ripening stages affects the reliability of the results obtained. In this work, these changes were studied in Nebbiolo grapes harvested during five consecutive weeks and then separated according to three density classes. The changes observed in chemical and mechanical parameters through the ripening process are more related to berry density than harvest date. Therefore, the winemaker has to select the flotation density according to the objective quality properties of the wine to be elaborated. On the other hand, the stiffer grapes were associated with a higher accumulation of proanthocyanidins. The harder grapes provided the higher concentration and extractability of flavanols reactive to vanillin, whereas the thicker ones facilitated the extraction of proanthocyanidins.

Study Objective: To compare surgical outcomes of laparoscopic hysterectomy for benign diseases according to the uterine weight., Design: Retrospective study (Canadian Task Force classification II-3)., Setting: Teaching and research hospital, a tertiary center., Patients: Women undergoing laparoscopic hysterectomy for benign diseases., Interventions: Patients were divided into three groups according to the uterine weight: <250 g (n = 1300), 250 to 500 g (n = 614), and >500 g (n = 178)., Measurements and Main Results: Primary outcomes were differences in conversion rates, operating time, and blood loss. Secondary outcomes were differences in length of hospital stay, time to first bowel movement, time of bladder catheterization, and complications. Operating time increased according to the uterine weight (116.5 vs 124.1 vs 133 minutes; p <.001). The rate of conversion was statistically higher only for patients with uteri >500 g (3.3% vs 5% vs 13.5%; p <.001). However, the difference between preoperative and postoperative hemoglobin levels was equivalent for the three groups, as well as the overall rates of minor and major intraoperative complications. There was no difference in the time of bladder catheterization, time to first bowel movement, length of hospital stay, and incidence of minor and major postoperative complications among the three groups., Conclusion: Despite longer operating time, there is no increase in the intraoperative or postoperative complication rates in those patients with enlarged uteri undergoing laparoscopic hysterectomy. Only conversion is higher in patients with uteri >500 g., (Copyright © 2011 AAGL. Published by Elsevier Inc. All rights reserved.)

Objective: To describe different approaches for diagnosis and management of proximal ectopic pregnancies (PP) in general population., Design: Observational population based-study., Setting: Regional ectopic pregnancy registry., Patient(s): Eighty-six PP registered from 1992 to 2008., Intervention(s): Surgical (radical or conservative), medical, or combined therapies., Main Outcome Measure(s): Epidemiologic characteristics, clinical presentation, hCG level, treatments performed, failure rate, and recurrence., Result(s): Mean gestational age was 48.2 days. Estimated incidence of PP was 2.7%. Abdominal pain and vaginal bleeding were the commonest symptoms. Two patients were admitted in hypovolemic shock. Diagnostic modalities included transvaginal ultrasound, abdominal ultrasonography, and laparoscopy in 38 (44%), 7 (8%), and 39 (45%) cases, respectively. Mean hCG level was 10,759 IU/L. Thirty-four patients underwent primary cornual resection (39.5%) by laparoscopy (n = 32) or laparotomy (n = 2). Twenty-seven patients (31.4%) underwent primary conservative surgery by laparoscopy: cornuostomy (n = 18) or extended salpigostomy (n = 9). Primary medical treatment with methotrexate was attempted in 14 patients (16.3%). Expectant management was attempted in one case (1.2%). Eleven cases received combined therapies (11.6%). Failure rates for medical and surgical treatments were 35.7% and 28%, respectively. No failures were noted among patients who received combined therapies., Conclusion(s): Proximal ectopic pregnancy remains a life-threatening condition. Diagnosis is challenging and requires a high index of suspicion. Despite available conservative strategies, management of PP remains heterogeneous., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Polysensitization is quite frequent in allergic children and may cause difficulties for the allergist in prescribing allergen-specific immunotherapy. This study aimed at evaluating the clinical effectiveness of 1 year of sublingual immunotherapy (SLIT) in a cohort of Italian allergic children with polysensitization. This open study was performed on 51 polysensitized children (34 boys; mean age, 11.8 years; range, 5.2-17.7 years) with allergic rhinitis and/or mild to moderate asthma. All of them were treated with SLIT for 1 year. The kind and the number of prescribed allergen extracts, the type of diagnosis, the severity of symptoms, and the use of drugs were evaluated at baseline and after 1 year. The adverse events to SLIT were also evaluated. Forty-two children were treated with a single extract, four with two different extracts and three with a mix of allergens. SLIT treatment induced a significant reduction in the number of sensitizations (p = 0.018); significant improvement of allergic rhinitis classification and severity; significant reduction of ocular, nasal, and bronchial symptoms (p < 0.01 for all); and drugs use (p < 0.01 for all drugs). No systemic reactions to SLIT were observed. This open study provides evidence that polysensitization is not an obstacle for prescribing SLIT in polysensitized children. Indeed, SLIT efficacy on clinical parameters is significant after 1 year and the therapy is safe.

Background: The natural history of respiratory allergy is commonly characterized by a worsening of symptom severity, frequent comorbidity of rhinitis and asthma, and polysensitization to aeroallergens. The polysensitization phenomenon starts since childhood and is rare to find monosensitized adult patients. However, there are few studies investigating the characteristics of polysensitized patients., Methods: This study was performed on a large cohort of patients with allergic rhinitis (assessed by ARIA criteria) and/or mild to moderate asthma (assessed by GINA). The kind and the number of sensitizations, their patterns, and the relation with quality of life (QoL) measured by the Juniper's RQLQ guestionnaire, were evaluated., Results: Globally 418 patients (50.2% males, 49.8% females, mean age 26.4 years, range 3.5-65 years, 64 smokers, 371 non-smokers) were enrolled: 220 had allergic rhinitis alone, and 198 allergic rhinitis and asthma. The mean number ofsensitizations was 2.6. Three hundred-five patients (73%) had persistent rhinitis (PER), 220 of them with moderate-severe form. There was no significant derence in rate of rhinitis and asthma in monosensitized or polysensitized patients. Most patients were sensitized to pollens, whereas only 24.2% of them were sensitized to perennial allergens. Polysensitization was significantly associated with some issues of QoL, confirming previous findings, but not with number ofsensitizations., Conclusions: This study provides data confirming for poly-sensitized patients the relevance of ARIA classification of AR. PER is the most common form of AR in this cohort, symptoms are frequently moderate-severe, and asthma is present in about the half of patients with AR.

Evidence has been cumulated during the last years concerning the immaturity of the cells involved in the local and systemic aspects of allergic inflammation. Hematopoietic precursors (HPC) are mobilized from the bone matrix as multipotent cells or, more often, as progenitors that, after the initial white-lineage commitment reach through the peripheral blood (PB) their final destinations constituted by the target organs of allergy. Although several studies have investigated the CD34+ cells traffic and location at the level of the inflamed peripheral mucosae in allergic populations, limited information is available on their behaviour on the time-course of infectious diseases. The current study thus was designed to asses the peripheral traffic of CD34+ HPC during the infectious inflammation. To this end CD34+ HPCs have been enumerated, by flow-cytometric techniques, in PB of 24 adult healthy beings (Group A), 24 adult subjects with symptomatic extrinsic allergy (Group B) and in PB of 24 adult patients hospitalised for febrile infectious pathology (Group C). CD34+ cell values ranged 0.01-0.08% with a median of 0.03 in Group A. In Group B values ranged 0.17-0.75% with a median of 0.28 and in Group C values ranged 0.00-0.12% with a median of 0.07. Variance analysis test among the three groups was statistically significant (p<0.001) supporting the conclusion that CD34+ HPC mobilizing and increased peripheral traffic is an unique feature of the allergic inflammation.

Venom immunotherapy has proven a very effective method for the treatment of allergy to Hymenoptera venom. Aqueous instead of depot extracts are prevalently used for this immunotherapy. The advantage of using aqueous extracts has not been fully investigated. We made an open, non-controlled study on 45 subjects sensitized to either Apis mellifera or Vespula spp. Patients were assigned to either a depot (N=27) or an aqueous (N=18) immunotherapy regimen, and side effects were monitored during the induction and the 3-year maintenance phase. The effect of naturally occurring stings during the treatment and after its interruption was recorded as well. Side effects were less frequent with the depot extract both on a "per patient" (22.2% versus 50.0%) and on a "per dose" (2.9% versus 10,2%) basis (p=0.026 and p<0.000, respectively). Better tolerance was mainly due to the lower frequency of local side effects occurring at early times after vaccination. The efficacy of vaccination was comparable in the 2 cohorts, as expected. We conclude that depot immunotherapy to Hymenoptera venom should be preferred to aqueous immunotherapy for the lower occurrence of local side effects. This might influence a better compliance with this potentially life-saving treatment.

We used pulsed laser imaging to measure the development and dissipation of Ca(2+) gradients evoked by the activation of voltage-sensitive Ca(2+) channels in adrenal chromaffin cells. Ca(2+) gradients appeared rapidly (<5 ms) upon membrane depolarization and dissipated over several hundred milliseconds after membrane repolarization. Dissipation occurred with an initial fast phase, as the steep gradient near the membrane collapsed, and a slower phase as the remaining shallow gradient dispersed. Inhibition of active Ca(2+) uptake by the endoplasmic reticulum (thapsigargin) and mitochondria (carbonylcyanide p-trifluoro-methoxyphenylhydrazone/oligomycin) had no effect on the size of Ca(2+) changes or the rate of gradient dissipation, suggesting that passive endogenous Ca(2+) buffers are responsible for the slow Ca(2+) redistribution. We used a radial diffusion model incorporating Ca(2+) diffusion and binding to intracellular Ca(2+) buffers to simulate Ca(2+) gradients. We included a 3D optical sectioning model, simulating the effects of out-of-focus light, to allow comparison with the measured gradients. Introduction of a high-capacity immobile Ca(2+) buffer, with a buffer capacity on the order of 1000 and appropriate affinity and kinetics, approximated the size of the Ca(2+) increases and rate of dissipation of the measured gradients. Finally, simulations without exogenous buffer suggest that the Ca(2+) signal due to Ca(2+) channel activation is restricted by the endogenous buffer to a space less than 1 microm from the cell membrane.

The consequences of an extrasystole (ES) on cardiac muscle's energetics and Ca2+ homeostasis were investigated in the beating heart. The fraction of heat release related to pressure development (pressure dependent) and pressure-independent heat release were measured during isovolumic contractions in arterially perfused rat ventricle. The heat release by a contraction showed two pressure-independent components (H1 and H2) of short evolution and a pressure-dependent component (H3). The additional heat released by ES was decomposed into one pressure-independent (H'2) and one pressure-dependent (H'3) component with time courses similar to those of control components H2 and H3. ES also induced the potentiation of pressure development (P) and heat release during the postextrasystolic (PES) beat. The slope of the linear relationship between pressure-dependent heat and pressure maintenance was similar in control, ES, and PES contractions (0.08 +/- 0.01, 0.10 +/- 0.02, and 0.08 +/- 0.01 mJ. g-1. mmHg-1. s-1, respectively). The potentiation of H2 (heat component related with Ca2+ removal processes) in PES was equal to H'2 at 0.3, 0.5, 1, and 2 mM Ca2+, suggesting that the extra amount of Ca2+ mobilized during ES was recycled in PES. Pretreatment with 1 mM caffeine to deplete sarcoplasmic reticulum Ca2+ content inhibited both the mechanical and energetic potentiation of PES. However, the heat released and the pressure developed during ES were not changed by sarcoplasmic reticulum depletion. The results suggest that 1) the source of Ca2+ for ES would be entirely extracellular, 2) the Ca2+ entered during ES is accumulated in the sarcoplasmic reticulum, and 3) the Ca2+ stored by the sarcoplasmic reticulum during ES induces an increased contribution of this organelle during PES compared with the normal contraction.

Background: The effect of long-term smoking on coronary vasomotion and vasodilator capacity in healthy smokers is unknown., Methods and Results: Myocardial blood flow (MBF) was quantified with [13N]ammonia and positron emission tomography (PET) at rest, during cold pressor testing (endothelium-dependent vasomotion), and during dipyridamole-induced hyperemia in 16 long-term smokers and 17 nonsmokers. MBF at rest did not differ between the 2 groups. Cold induced similar increases in rate-pressure product (RPP) in smokers and nonsmokers. However, MBF increased only in nonsmokers and was, during cold, higher than in smokers (0.91+/-0.18 versus 0.78+/-0.14 mL x g(-1) x min(-1), P<0.05). MBF normalized to the RPP (derived from the ratio of MBF ([milliliters per gram per minute] to RPP [beats per minute times millimeters of mercury] times 10000) declined in smokers but remained unchanged in nonsmokers (0.86+/-0.10 versus 0.72+/-0.11, P=0.0006, and 0.99+/-0.25 versus 0.96+/-0.27, P=NS). The hyperemic response to dipyridamole and the myocardial flow reserve did not differ between the 2 groups. In a multiple regression model adjusted for age, sex, serum lipid levels, years of smoking, and pack-years, years of smoking was the strongest predictor of the normalized blood flow response to cold (P<0.001), followed by the HDL/LDL ratio., Conclusions: The normal hyperemic response to dipyridamole in long-term smokers indicates a preserved endothelium-independent coronary vascular smooth muscle relaxation, whereas the abnormal response to cold suggests a defect in coronary vasomotion likely located at the level of the coronary endothelium. Its severity depends on the total exposure time to smoking.

The specific removal of negatively-charged sialic acid by neuraminidase produces a large increase in cardiac myocyte Ca uptake (17.3 +/- 1.1 mmol Ca/kg dry weight) and marked cell contracture. Importantly, the insertion of the negatively-charged amphiphile dodecyl sulfate in the sarcolemma eliminates the increased calcium uptake and preserves contractile function. In the present study, we further examine the role of sialic acid-Ca interaction and, specifically, the role of gangliosides (sialic acid-containing glycolipids) in cardiac cells' Ca permeability. Neonatal cell culture and adult ventricular myocytes were used. The major findings of this study are: (1) while dodecyl sulfate inhibits cellular calcium uptake and contracture development induced by sialic acid removal, cationic and neutral amphiphiles are without effect. (2) Ca channel blockers (nifedipine and protamine) and the Na/Ca exchange inhibitor Ni do not modify the effect of sialic acid removal. (3) A non-classical-channel related whole-cell current appears and increases after 21 +/- 2.2 min treatment with 0.02 U/ml neuraminidase (n = 4). Incubation with neuraminidase in the presence of dodecyl sulfate greatly delays the appearance of these currents to 44.4 +/- 6.1 min (n = 4). (4) The use of a specific probe for GM1 ganglioside, the cholera toxin B subunit (3 micrograms/ml), induces a moderate but clear increase in cellular Ca (1.63 +/- 0.3 mmol Ca kg dry weight; n = 8). However, this increase was not modified by treatment with dodecyl sulfate. (5) Finally, 50 mU/ml endoglycoceramidase, an enzyme which specifically cleaves the link between the sialic acid-containing oligosaccharide and ceramide of gangliosides, induced a significant increase in Ca uptake (4.4 +/- 0.9 mmol Ca kg dry weight, n = 4). These results indicate the importance of negatively charged sialic acid-containing gangliosides in the maintenance of cardiac cell physiological Ca permeability. The increase in Ca uptake induced by the removal of sialic acid seems to be mediated by development of a Ca "leak" via other than classical cation channels.

Cardiac myocyte Ca transport systems, such as sarcoplasmic reticulum Ca-ATPase and sarcolemmal Na/Ca exchange (Na/Ca), are critically dependent on temperature. The purpose of this work was to study the effect of temperature on cellular Ca compartmentation and its exchange characteristics in intact functional neonatal cultured myocytes. The Na/Ca mediated Ca exchange (CaNa/Ca)--including its sarcoplasmic reticulum (SR) and sarcolemmal (SL) contributions, a slow exchange component related to mitochondrial Ca and the La displaceable Ca pool were studied combining isotopic and gas-dissection techniques for membrane isolation. The major findings of this study are: (i) The amount of Ca exchanged through CaNa/Ca is clearly dependent on temperature (Q10 approximately 1.6) in the range studied (17-37 degrees C); (ii) the addition of 1 microM nifedipine does not modify the temperature dependence of CaNa/Ca; (iii) the sarcolemmal bound fraction contributing to CaNa/Ca is not changed by temperature; (iv) the increase in CaNa/Ca with temperature is explained by an increment in the contribution of SR-Ca to CaNa/Ca; (v) a fraction of SR which does not exchange via CaNa/Ca at low temperatures can be released and mobilized by caffeine-this caffeine sensitive fraction is reduced as temperature is increased and is no longer measurable as a separate entity at 37 degrees C; (vi) if we consider (iv) and (v) together, SR content would be temperature dependent with a Q10 of approximately 1.5; (vii) a La displaceable pool, which represents over 66% of the total exchangeable Ca, increases in the range of 22-33 degrees C with a Q10 of 1.25 which is consistent with a pool distribution of 70% SL-bound and 30% SR-derived [Post J.A., Langer G.A. Cellular origin of the rapidly exchangeable calcium pool in the cultured neonatal rat heart cell. Cell Calcium 1992; 13: 627-634]; and (viii) the rate constant for the mitochondrial Ca component increases by 60% from 22 degrees C to 37 degrees C, but Ca content in this organelle is not modified over this temperature range.

In the isolated rat left atria the influence of rest intervals on the force developed by the first post rest beat (PRB) was studied. Under control conditions the force developed by the PRB increased (respect to previous steady state at 0.5 Hz) with the increase of the rest interval until 20 sec of pause and decreased with longer intervals. In the presence of caffeine (1 or 4 mM plus high [Ca]0) there was a monotonous fall of the PRB as a function of the rest interval. When extracellular calcium was replaced by Sr the tension developed by PRB vs. rest interval curve rose with a slope lower than the control one and reached the peak at 60 sec. At saturation levels of [Ca]0 the PRB tension development did not vary up to 20 sec pause but the decreasing phase observed after 20 sec of rest interval was still present. At 0.5 mM [Ca]0 the response was similar to control curve. The results in the presence of caffeine and strontium suggest that, in rat atria, the rest potentiation appears to be dependent on the release of calcium from intracellular stores (sarcoplasmic reticulum). This is consistent with the hypothesis proposing that longer resting periods provide a longer interval for the transfer of Ca from uptake to release sites in the sarcoplasmic reticulum.