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The article discusses the use of tritium (3H) and cesium (137Cs) as temporal markers in ice cores extracted from temperate glaciers. We present a complete tritium profile for a 46 m ice core drilled from the Adamello Glacier, a temperate glacier in the Italian Alps, and compare it to the 137Cs profile from the same ice core. Our analysis reveals tritium contamination between 19 and 32 m of depth, which can be attributed to the global radioactive fallout caused by atmospheric nuclear-bomb testing that took place in the 1950s and 1960s. Results show that the radioactive peak associated with 1963 does not occur at the same depth for both 3H and 137Cs; instead, the tritium peak is 1.5 m above the cesium one. Our hypothesis is that this misalignment is caused by meltwater-induced post-depositional processes that affect 137Cs, which is more sensitive to percolation than 3H. The total inventory of 137Cs in this ice core is also among the lowest ever reported, providing additional evidence that the presence of meltwater has affected the distribution of this radionuclide within the ice. In contrast, the total tritium inventory is comparable to what is reported in the literature, making it a more reliable temporal marker for temperate glaciers.

Thanks to its insolubility, mineral dust is considered a stable proxy in polar ice cores. With this study we show that the Talos Dome ice core (TALDICE, Ross Sea sector of East Antarctica) displays evident and progressive signs of post-depositional processes affecting the mineral dust record below 1000 m deep. We apply a suite of established and cutting-edge techniques to investigate the properties of dust in TALDICE, ranging from concentration and grain size to elemental composition and Fe mineralogy. Results show that through acidic/oxidative weathering, the conditions of deep ice at Talos Dome promote the dissolution of specific minerals and the englacial formation of others, affecting primitive dust features. The expulsion of acidic atmospheric species from ice grains and their concentration in localized environments is likely the main process responsible for englacial reactions. Deep ice can be seen as a “geochemical reactor” capable of fostering complex reactions which involve both soluble and insoluble impurities. Fe-bearing minerals can efficiently help in exploring such transformations.

Dating glaciers is an arduous yet essential task in ice core studies, which becomes even more challenging when the glacier is experiencing mass loss in the accumulation zone as result of climate warming, leading to an older ice surface of unknown age. In this context, we dated a 46 m deep ice core from the Central Italian Alps retrieved in 2016 from the Adamello glacier in the locality Pian di Neve (3100 m a.s.l.). Here we present a timescale for the core obtained by integrating results from the analyses of the radionuclides 210Pb and 137Cs with annual layer counting derived from pollen and refractory black carbon concentrations. Our results clearly indicate that the surface of the glacier is older than the drilling date of 2016 by about 20 years and that the 46 m ice core reaches back to around 1944. For the period of 1995–2016 the mass balance at the drilling site (former accumulation zone) decreased on average of about 1 m w.e. a−1 compared to the period 1963–1986. Despite the severe mass loss affecting this glacier even in the former accumulation zone, we show that it is possible to obtain a reliable timescale for such a temperate glacier using black carbon and pollen seasonality in combination with radionuclides 210Pb and 137Cs. Our results are therefore very encouraging and open new perspectives on the potential of such glaciers as informative palaeoarchives.

A deeper understanding of past atmospheric circulation variability in the Central Andes is a high-priority topic in paleoclimatology mainly because of the necessity to validate climate models used to predict future precipitation trends and to develop mitigation and/or adaptation strategies for future climate change scenarios in this region. Within this context, we here investigate an 18-year firn core drilled at Nevado Illimani in order to interpret its mineral dust record in relation to seasonal processes, in particular atmospheric circulation and deep convection. The core was dated by annual layer counting based on seasonal oscillations of dust, calcium, and stable isotopes. Geochemical and mineralogical data show that dust is regionally sourced in winter and summer. During austral summer (wet season), an increase in the relative proportion of giant dust particles (∅>20 µm) is observed, in association with oscillations of stable isotope records (δD, δ18O). It seems that at Nevado Illimani both the deposition of dust and the isotopic signature of precipitation are influenced by atmospheric deep convection, which is also related to the total amount of precipitation in the area. This hypothesis is corroborated by regional meteorological data. The interpretation of giant particle and stable isotope records suggests that downdrafts due to convective activity promote turbulent conditions capable of suspending giant particles in the vicinity of Nevado Illimani. Giant particles and stable isotopes, when considered together, can be therefore used as a new proxy for obtaining information about deep convective activity in the past.

Cryoconite is rich in natural and artificial radioactivity, but a discussion about its ability to accumulate radionuclides is lacking. A characterization of cryoconite from two Alpine glaciers is presented here. Results confirm that cryoconite is significantly more radioactive than the matrices usually adopted for the environmental monitoring of radioactivity, such as lichens and mosses, with activity concentrations exceeding 10 000 Bq kg−1 for single radionuclides. This makes cryoconite an ideal matrix to investigate the deposition and occurrence of radioactive species in glacial environments. In addition, cryoconite can be used to track environmental radioactivity sources. We have exploited atomic and activity ratios of artificial radionuclides to identify the sources of the anthropogenic radioactivity accumulated in our samples. The signature of cryoconite from different Alpine glaciers is compatible with the stratospheric global fallout and Chernobyl accident products. Differences are found when considering other geographic contexts. A comparison with data from literature shows that Alpine cryoconite is strongly influenced by the Chernobyl fallout, while cryoconite from other regions is more impacted by events such as nuclear test explosions and satellite reentries. To explain the accumulation of radionuclides in cryoconite, the glacial environment as a whole must be considered, and particularly the interaction between ice, meltwater, cryoconite and atmospheric deposition. We hypothesize that the impurities originally preserved into ice and mobilized with meltwater during summer, including radionuclides, are accumulated in cryoconite because of their affinity for organic matter, which is abundant in cryoconite. In relation to these processes, we have explored the possibility of exploiting radioactivity to date cryoconite.

The input of mineral dust from arid regions impacts snow optical properties. The induced albedo reduction generally alters the melting dynamics of the snowpack, resulting in earlier snowmelt. In this paper, we evaluate the impact of dust depositions on the melting dynamics of snowpack at a high-elevation site (2160 m) in the European Alps (Torgnon, Aosta Valley, Italy) during three hydrological years (2013–2016). These years were characterized by several Saharan dust events that deposited significant amounts of mineral dust in the European Alps. We quantify the shortening of the snow season due to dust deposition by comparing observed snow depths and those simulated with the Crocus model accounting, or not, for the impact of impurities. The model was run and tested using meteorological data from an automated weather station. We propose the use of repeated digital images for tracking dust deposition and resurfacing in the snowpack. The good agreement between model prediction and digital images allowed us to propose the use of an RGB index (i.e. snow darkening index – SDI) for monitoring dust on snow using images from a digital camera. We also present a geochemical characterization of dust reaching the Alpine chain during spring in 2014. Elements found in dust were classified as a function of their origin and compared with Saharan sources. A strong enrichment in Fe was observed in snow containing Saharan dust. In our case study, the comparison between modelling results and observations showed that impurities deposited in snow anticipated the disappearance of snow up to 38 d a out of a total 7 months of typical snow duration. This happened for the season 2015–2016 that was characterized by a strong dust deposition event. During the other seasons considered here (2013–2014 and 2014–2015), the snow melt-out date was 18 and 11 d earlier, respectively. We conclude that the effect of the Saharan dust is expected to reduce snow cover duration through the snow-albedo feedback. This process is known to have a series of further hydrological and phenological feedback effects that should be characterized in future research.

A first assessment of the main climatic drivers that modulate the tree-ring width (RW) and maximum latewood density (MXD) along the Italian Peninsula and northeastern Sicily was performed using 27 forest sites, which include conifers (RW and MXD) and broadleaves (only RW). Tree-ring data were compared using the correlation analysis of the monthly and seasonal variables of temperature, precipitation and standardized precipitation index (SPI, used to characterize meteorological droughts) against each species-specific site chronology and against the highly sensitive to climate (HSTC) chronologies (based on selected indexed individual series). We find that climate signals in conifer MXD are stronger and more stable over time than those in conifer and broadleaf RW. In particular, conifer MXD variability is directly influenced by the late summer (August, September) temperature and is inversely influenced by the summer precipitation and droughts (SPI at a timescale of 3 months). The MXD sensitivity to August–September (AS) temperature and to summer drought is mainly driven by the latitudinal gradient of summer precipitation amounts, with sites in the northern Apennines showing stronger climate signals than sites in the south. Conifer RW is influenced by the temperature and drought of the previous summer, whereas broadleaf RW is more influenced by summer precipitation and drought of the current growing season. The reconstruction of the late summer temperatures for the Italian Peninsula for the past 300 years, based on the HSTC chronology of conifer MXD, shows a stable model performance that underlines periods of climatic cooling (and likely also wetter conditions) in 1699, 1740, 1814, 1914 and 1938, and follows well the variability of the instrumental record and of other tree-ring-based reconstructions in the region. Considering a 20-year low-pass-filtered series, the reconstructed temperature record consistently deviates

In this paper we present a method to detect airflow through ice caves and to quantify the corresponding airflow speeds by the use of temperature loggers. The time series of temperature observations at different loggers are cross-correlated. The time shift of best correlation corresponds to the travel time of the air and is used to derive the airflow speed between the loggers. We apply the method to test data observed inside Schellenberger Eishöhle (ice cave). The successful determination of airflow speeds depends on the existence of distinct temperature variations during the time span of interest. Moreover the airflow speed is assumed to be constant during the period used for the correlation analysis. Both requirements limit the applicability of the correlation analysis to determine instantaneous airflow speeds. Nevertheless the method is very helpful to characterize the general patterns of air movement and their slow temporal variations. The correlation analysis assumes a linear dependency between the correlated data. The good correlation we found for our test data confirms this assumption. We therefore in a second step estimate temperature biases and scale factors for the observed temperature variations by a least-squares adjustment. The observed phenomena, a warming and an attenuation of temperature variations, depending on the distance the air traveled inside the cave, are explained by a mixing of the inflowing air with the air inside the cave. Furthermore we test the significance of the determined parameters by a standard F test and study the sensitivity of the procedure to common manipulations of the original observations like smoothing. In the end we will give an outlook on possible applications and further development of this method.

Mineral dust plays an important role in the climate system by interacting with radiation, clouds, and biogeochemical cycles. In addition, natural archives show that the dust cycle experienced variability in the past in response to global and local climate change. The compilation of the DIRTMAP (Dust Indicators and Records from Terrestrial and MArine Palaeoenvironments) paleodust data sets in the last 2 decades provided a benchmark for paleoclimate models that include the dust cycle, following a time slice approach. We propose an innovative framework to organize a paleodust data set that builds on the positive experience of DIRTMAP and takes into account new scientific challenges by providing a concise and accessible data set of temporally resolved records of dust mass accumulation rates and particle grain size distributions. We consider data from ice cores, marine sediments, loess–paleosol sequences, lake sediments, and peat bogs for this compilation, with a temporal focus on the Holocene period. This global compilation allows the investigation of the potential, uncertainties, and confidence level of dust mass accumulation rate reconstructions and highlights the importance of dust particle size information for accurate and quantitative reconstructions of the dust cycle. After applying criteria that help to establish that the data considered represent changes in dust deposition, 45 paleodust records have been identified, with the highest density of dust deposition data occurring in the North Atlantic region. Although the temporal evolution of dust in the North Atlantic appears consistent across several cores and suggests that minimum dust fluxes are likely observed during the early to mid-Holocene period (6000–8000 years ago), the magnitude of dust fluxes in these observations is not fully consistent, suggesting that more work needs to be done to synthesize data sets for the Holocene. Based on the data compilation, we used the Community Earth System Model to estimate the mass balance of and variability in the global dust cycle during the Holocene, with dust loads ranging from 17.2 to 20.8 Tg between 2000 and 10 000 years ago and with a minimum in the early to mid-Holocene (6000–8000 years ago).

Central East Antarctic ice cores preserve stratigraphic records of mineral dust originating from remote sources in the Southern Hemisphere, and represent useful indicators of climatic variations on glacial-interglacial time scales. The peripheries of the East Antarctic Ice Sheet, where ice-free areas with the potential to emit dust exist, have been less explored from this point of view. Here, we present a new profile of dust deposition flux and grain size distributions from an ice core drilled at Talos Dome (TALDICE, Northern Victoria Land, East Antarctica), where there is a significant input of dust from proximal Antarctic ice-free areas. We analyze dust and stable water isotopes variations from the Last Glacial Maximum to the Late Holocene, and compare them to the EPICA Dome C profiles from central East Antarctica. The smaller glacial-interglacial variations at Talos Dome compared to Dome C and a distinctive decreasing trend during the Holocene characterize the TALDICE dust profile. By deciphering the composite dust signal from both remote and local sources, we show the potential of this combined proxy of source activity and atmospheric transport to give information on both regional and larger spatial scales. In particular, we show how a regional signal, which we relate to the deglaciation history of the Ross Sea embayment, can be superimposed to the broader scale glacial-interglacial variability that characterizes other Antarctic sites.

A simple, practical plan for reliably estimating mite densities overcomes problems of quantitative sampling.

Study Objective: To evaluate recurrence rate and pattern in apparently early-stage endometrial cancer (EC) treated with minimally invasive surgery (MIS) and compare it to the "historical" populations treated by laparotomy. Secondary outcomes were to establish if, among MIS recurrent patients, intermediate-high/high-risk patients presented the same recurrence pattern compared to those at low/intermediate-risk and to evaluate time to first recurrence (TTR) of the study population., Design: Multicenter retrospective observational study., Setting: Five Italian Gynecologic Oncology referral centers., Patients: All patients with proven recurrence of apparently early-stage EC treated with MIS from January 2017 to June 2022 . The laparotomic historical cohort was obtained from Laparoscopy Compared With Laparotomy for Comprehensive Surgical Staging of Uterine Cancer: Gynecologic Oncology Group Study (LAP2) and Laparoscopic Approach to Cancer of the Endometrium trials., Interventions: Evaluation of recurrence rate and pattern., Measurements and Main Results: Seventy-seven recurrences occurred on the total of 1028 patients treated with MIS for apparently early-stage EC during a median follow-up time of 36 months. The rate of recurrence in our cohort did not differ significantly from the rate of the historical cohort (7.4% vs 7.9%, odds ratio 0.9395, 95% CI 0.6901-1.2792). No significant differences were noticed for local, abdominal, nodal, and multiple site recurrence patterns; distant site recurrence appeared more likely in patients from the historical cohort. Postoperative low/intermediate risk patients had a higher likelihood of local recurrence compared to intermediate-high/high risk patients. Mean TTR was 19 months. No significant difference of TTR was observed for each pattern of recurrence compared to others., Conclusion: MIS appears to be safe for the treatment of early-stage EC. We did not identify any recurrence pattern specifically associated with MIS in early-stage EC., (Copyright © 2024 AAGL. Published by Elsevier Inc. All rights reserved.)

Background: The rate of concurrent endometrial cancer (EC) in atypical endometrial hyperplasia (AEH) can be as high as 40%. Some patient characteristics showed associations with this occurrence. However, their real predictive power with related validation has yet to be discovered. The present study aimed to assess the performance of various models based on patient characteristics in predicting EC in women with AEH., Methods: This is a retrospective multi-institutional study including women with AEH undergoing definitive surgery. The women were divided according to the final histology (EC vs. no-EC). The available cases were divided into a training and validation set. Using k-fold cross-validation, we built many predictive models, including regressions and artificial neural networks (ANN)., Results: A total of 193/629 women (30.7%) showed EC at hysterectomy. A total of 26/193 (13.4%) women showed high-risk EC. Regression and ANN models showed a prediction performance with a mean area under the curve of 0.65 and 0.75 on the validation set, respectively. Among the best prediction models, the most recurrent patient characteristics were age, body mass index, Lynch syndrome, diabetes, and previous breast cancer. None of these independent variables showed associations with high-risk diseases in women with EC., Conclusions: Patient characteristics did not show satisfactory performance in predicting EC in AEH. Risk stratification in AEH based mainly on patient characteristics may be clinically unsuitable.

Introduction: Oncovascular surgery (the removal of major blood vessels infiltrated by cancer) is challenging but can be key to achieve complete cytoreduction in patient with advanced ovarian cancer. The aim of this study was to review the literature on oncovascular surgery in ovarian cancer and to report the details of all the cases performed at our institution., Methods: We retrospectively reviewed the database of ovarian cancer patients who underwent debulking surgery at the Department of Obstetrics and Gynecology of Verona University between January 2021 and 2023. Patients with at least one major vessel resection during cytoreduction were identified. We then systematically review the literature searching Pubmed and Embase from inception to January 2023 to report all cases of surgery for ovarian cancer with concomitant major vessel resection., Results: Five patients with advanced/recurrent ovarian cancer underwent major vascular resection at our institution. Vascular involvement was preoperatively identified in all cases and no case of vascular resection was performed after accidental injury. The major vessels removed were the inferior vena cava (n = 2), the common iliac veins (n = 2), the external iliac arteries (n = 2), the left common iliac artery (n = 1), and the left external iliac vein (n = 1). All patients underwent other non-gynecological cytoreductive procedures prior to vessel removal and had R0 obtained. Three (60%) patients experienced one or more postoperative complications. The literature search identified a total of seven cases of major vessels resection in ovarian cancer surgery. A single or multiple major vessels were removed in two (28.6%) and five (72.4%) cases, respectively. All the seven patients underwent vascular reconstruction. Four (57.1%) patients reported postoperative complications. Overall, 66.7% of the 12 total identified patients were free from disease at the last follow-up [median 15.5 months (range 5-25)]., Conclusions: Oncovascular surgery is feasible in selected patients with ovarian cancer, provided that a multidisciplinary approach with customized care is available., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the performance of third-trimester ultrasound for the diagnosis of clinically significant placenta accreta spectrum disorder (PAS) in women with low-lying placenta or placenta previa., Methods: This was a prospective multicenter study of pregnant women aged ≥ 18 years who were diagnosed with low-lying placenta (< 20 mm from the internal cervical os) or placenta previa (covering the internal cervical os) on ultrasound at ≥ 26 + 0 weeks' gestation, between October 2014 and January 2019. Ultrasound suspicion of PAS was raised in the presence of at least one of these signs on grayscale ultrasound: (1) obliteration of the hypoechogenic space between the uterus and the placenta; (2) interruption of the hyperechogenic interface between the uterine serosa and the bladder wall; (3) abnormal placental lacunae. Histopathological examinations were performed according to a predefined protocol, with pathologists blinded to the ultrasound findings. To assess the ability of ultrasound to detect clinically significant PAS, a composite outcome comprising the need for active management at delivery and histopathological confirmation of PAS was considered the reference standard. PAS was considered to be clinically significant if, in addition to histological confirmation, at least one of these procedures was carried out after delivery: use of hemostatic intrauterine balloon, compressive uterine suture, peripartum hysterectomy, uterine/hypogastric artery ligation or uterine artery embolization. The diagnostic performance of each ultrasound sign for clinically significant PAS was evaluated in all women and in the subgroup who had at least one previous Cesarean section and anterior placenta. Post-test probability was assessed using Fagan nomograms., Results: A total of 568 women underwent transabdominal and transvaginal ultrasound examinations during the study period. Of these, 95 delivered in local hospitals, and placental pathology according to the study protocol was therefore not available. Among the 473 women for whom placental pathology was available, clinically significant PAS was diagnosed in 99 (21%), comprising 36 cases of placenta accreta, 19 of placenta increta and 44 of placenta percreta. The median gestational age at the time of ultrasound assessment was 31.4 (interquartile range, 28.6-34.4) weeks. A normal hypoechogenic space between the uterus and the placenta reduced the post-test probability of clinically significant PAS from 21% to 5% in women with low-lying placenta or placenta previa in the third trimester of pregnancy and from 62% to 9% in the subgroup with previous Cesarean section and anterior placenta. The absence of placental lacunae reduced the post-test probability of clinically significant PAS from 21% to 9% in women with low-lying placenta or placenta previa in the third trimester of pregnancy and from 62% to 36% in the subgroup with previous Cesarean section and anterior placenta. When abnormal placental lacunae were seen on ultrasound, the post-test probability of clinically significant PAS increased from 21% to 59% in the whole cohort and from 62% to 78% in the subgroup with previous Cesarean section and anterior placenta. An interrupted hyperechogenic interface between the uterine serosa and bladder wall increased the post-test probability for clinically significant PAS from 21% to 85% in women with low-lying placenta or placenta previa and from 62% to 88% in the subgroup with previous Cesarean section and anterior placenta. When all three sonographic markers were present, the post-test probability for clinically significant PAS increased from 21% to 89% in the whole cohort and from 62% to 92% in the subgroup with previous Cesarean section and anterior placenta., Conclusions: Grayscale ultrasound has good diagnostic performance to identify pregnancies at low risk of PAS in a high-risk population of women with low-lying placenta or placenta previa. Ultrasound may be safely used to guide management decisions and concentrate resources on patients with higher risk of clinically significant PAS. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Gestational diabetes mellitus (GD) is characterized by glycemic and lipid metabolism alterations in an environment of low-grade inflammation. Our trial aimed to assess the effect of nutraceutical supplements (omega-3 fatty acids, anthocyanins, and alpha-cyclodextrins) in GD patients and evaluate the role of anthropometric, metabolic, and inflammatory parameters as biomarkers to identify subjects who require pharmacological hypoglycemic treatment during gestation. Pregnant women with GD at 24-28 weeks of gestation were enrolled in a double-blind trial and randomized to receive either nutraceutical supplements or a placebo for 12 weeks. No statistically significant differences were observed between the two groups in blood and urine measurements of metabolic, inflammatory, and antioxidant parameters. In the whole cohort, pre-pregnancy BMI and anthropometric measurements were significantly different in patients who required pharmacological intervention. These patients showed higher triglycerides, CRP, and insulin levels and gave birth to newborns with significantly higher weights. Subjects with a greater AA/EPA ratio had higher PAF levels and gave birth four days earlier. In conclusion, one-to-one nutritional coaching and poor compliance with nutraceutical supplementation might have outweighed the impact of this intervention. However, triglyceride concentration and the AA/EPA ratio seems to be a biomarker for higher inflammatory levels and GD candidates for pharmacological treatment. An adequate assumption of omega-3 in women with GD, either by a controlled diet or by nutraceutical supplementation, reduces the need for pharmacological therapy.

Objectives: To evaluate the failure rate and performance of cell-free DNA (cfDNA) testing as a first-line screening method for major trisomies, performed by two laboratories using different analytical methods: a targeted chromosome-selective method (Harmony ® prenatal Test) versus a home-brew genome-wide (GW) massively parallel sequencing method (HB-cfDNA test), and to evaluate the clinical value of incidental findings for the latter method., Methods: CfDNA testing was performed in 3137 pregnancies with the Harmony ® prenatal Test and in 3373 pregnancies with the HB-cfDNA test. Propensity score analysis was used to match women between both groups for maternal age, weight, gestational age at testing, in vitro fertilization, rate of twin pregnancies and that of aneuploidies. Detection rates for trisomy 21 were compared between the 2 laboratories. For the HB-cfDNA test, cases with rare incidental findings were reported, including their clinical follow-up., Results: The Harmony ® prenatal Test failed at the first attempt in 90 (2.9%) of 3114 women and the HB-cfDNA test in 413 (12.2%) of 3373 women. Postmatched comparisons of the women's characteristics indicate a significantly lower failure rate in the Harmony ® group (2.8%) than in the HB cfDNA group (12.4%; p  < .001). Of the 90 women in whom the Harmony ® prenatal Test failed, 61 had a repeat test, which still failed in 10, and of the 413 women in whom the HB-cfDNA test failed, 379 had a repeat test, which still failed in 110. The total failure rate after one or two attempts was therefore 1.3% (39/3114) for Harmony ® and 4.3% (144/3373) for the HB cfDNA test. After the first or second Harmony ® prenatal Test, a high-risk result was noted in 17 of the 17 cases with trisomy 21, in 5 of the seven cases with trisomy 18, and a no-call in two cases, and in the one case with trisomy 13. The respective numbers for the HB-cfDNA test are 17 of the 18 cases with trisomy 21, and a no-call in one case, 2 of the two cases with trisomy 18, and in 2 of the three cases with trisomy 13, and a no-call in one. Of the 3373 women with the HB-cfDNA test, a rare incidental finding was noted in 28 (0.8%) of the cases, of which only 2 were confirmed on amniocytes (one with microduplication 1q21.1q21.2 and one with a deletion Xp21.1), and in another case a deletion rather than a duplication of the long arm of chromosome 8 was found. In all 28 cases, there was normal clinical follow-up., Conclusions: Comparison of cfDNA testing between these two laboratories showed a four-fold lower failure rate with the Harmony ® prenatal Test, with a similar detection rate for trisomy 21. We showed no clinical relevance of disclosing additional findings beyond common trisomies with the GW HB-cfDNA test.

Introduction: Trophoblastic invasion and placental growth are critical for pregnancy outcome. The placental volume can be assessed by 3 D ultrasound using Virtual Organ Computer-aided Analysis (VOCAL). Epidemiological and clinical data suggest that there are two different clinical phenotypes of hypertensive disorders of pregnancy (HDP) that coexist at any gestational age: HDP associated to fetal growth impairment and HDP associated to appropriate for gestational age fetal growth. The aim of this study was to determine whether placental volume in the first trimester of pregnancy differs between women with HDP associated or not to fetal growth impairment and uncomplicated pregnancies., Methods: This is a retrospective cross-sectional study of prospectively recruited data in which maternal characteristics, Doppler velocimetry of uterine arteries, and three-dimensional (3 D) volume of the placenta were collected at 11 + 1 - 13 + 6 gestational weeks. The placental quotient (PQ) was calculated as placental volume/crown rump length., Results: In a 2-year period, we prospectively collected first trimester data of 1322 women. For the purposes of this cross-sectional study, 57 women that delivered a SGA fetus, 34 that developed HDP-AGA, and six that developed HDP-SGA, respectively, were included in the study as cases. The control group was made of 117 uncomplicated pregnancies. The PQ was higher in women with uncomplicated pregnancies (PQ median 16.36 cm 3 /cm) than in all other study groups (PQ in SGA: 13.02 cm 3 /cm, p  < .001; PQ in HDP-AGA: 12.65 cm 3 /cm, p  = .002; and PQ in women with HDP-SGA: 8.33 cm 3 /cm [IQR 6.50-10.13], p  < .001). The lowest PQ was observed in women with HDP-SGA and was significantly lower than PQ in either women with SGA or those with HDP-AGA ( p  = .02 and p  = .04, respectively). The mean uterine artery pulsatility index was the highest in women with HDP-SGA (median 2.30) compared to all other groups (uncomplicated pregnancies 1.48, p  < .0001; women with SGA 1.59, p  = .001; and women with HDP-AGA 1.75, p  = .009)., Discussion: Our findings suggest that HDP associated with SGA is characterized by impaired placental growth and perfusion as soon as in the first trimester of pregnancy. The role of PQ, isolated or in association with other biophysical parameters, to predict HDP with fetal growth impairment remains to be evaluated.

Objective: In this study we describe the management of women with gestational diabetes (GD) and an ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of the study is to evaluate whether coronavirus disease 2019 (COVID-19) can further complicate pregnancies, and if the protocol we usually use for GD pregnancies is also applicable to patients who have contracted a SARS-CoV-2 infection., Methods: This is a retrospective study analyzing all pregnant women with GD and concomitant COVID-19 admitted to our institution for antenatal care between March 1 and April 30, 2020., Results: Among pregnant women with GD and a concomitant SARS-CoV-2 infection, the mean age was 32.9 (SD 5.6) years. Two patients (33%) were of white racial origin and four (67%) were of non-white racial origin. All patients were diagnosed with COVID-19 during the third trimester of pregnancy. Two women were asymptomatic and four were symptomatic. Only two (33.3%) women received treatment with insulin. None of the patients required intensive care or mechanical ventilation. No complications were found among the neonates., Conclusion: COVID-19 was not found to worsen the prognosis of patients with GD or of their offspring. Glycemic monitoring, diet therapy, and insulin, when needed, are sufficient for good metabolic control and favorable maternal and fetal outcomes., (© 2020 International Federation of Gynecology and Obstetrics.)

Many interpretations have been proposed to explain the presence of jarosite within Martian surficial sediments, including the possibility that it precipitated within paleo-ice deposits owing to englacial weathering of dust. However, until now a similar geochemical process was not observed on Earth nor in other planetary settings. We report a multi-analytical indication of jarosite formation within deep ice. Below 1000 m depth, jarosite crystals adhering on residual silica-rich particles have been identified in the Talos Dome ice core (East Antarctica) and interpreted as products of weathering involving aeolian dust and acidic atmospheric aerosols. The progressive increase of ice metamorphism and re-crystallization with depth, favours the relocation and concentration of dust and the formation of acidic brines in isolated environments, allowing chemical reactions and mineral neo-formation to occur. This is the first described englacial diagenetic mechanism occurring in deep Antarctic ice and supports the ice-weathering model for jarosite formation on Mars, highlighting the geologic importance of paleo ice-related processes on this planet. Additional implications concern the preservation of dust-related signals in deep ice cores with respect to paleoclimatic reconstructions and the englacial history of meteorites from Antarctic blue ice fields.

Current biodiversity loss is a major concern and thus biodiversity assessment of modern ecosystems is compelling and needs to be contextualized on a longer timescale. High Throughput Sequencing (HTS) is progressively becoming a major source of data on biodiversity time series. In this multi proxy study, we tested, for the first time, the potential of HTS to estimate plant biodiversity archived in the surface layers of a temperate alpine glacier, amplifying the trnL barcode for vascular plants from eDNA of firn samples. A 573 cm long core was drilled by the Adamello glacier and cut into sections; produced samples were analyzed for physical properties, stable isotope ratio, and plant biodiversity by eDNA metabarcoding and conventional light microscopy analysis. Results highlighted the presence of pollen and plant remains within the distinct layers of snow, firn and ice. While stable isotope ratio showed a scarcely informative pattern, DNA metabarcoding described distinct plant species composition among the different samples, with a broad taxonomic representation of the biodiversity of the catchment area and a high-ranking resolution. New knowledge on climate and plant biodiversity changes of large catchment areas can be obtained by this novel approach, relevant for future estimates of climate change effects.

A 3800 year-long radiocarbon-dated and highly-resolved palaeoecological record from Lake Fimon (N-Italy) served to investigate the effects of potential teleconnections between North Atlantic and mid-to-low latitudes at the transition from Marine Isotope Stage (MIS) 3 to 2. Boreal ecosystems documented in the Fimon record reacted in a sensitive way to millennial and sub-millennial scale Northern Hemisphere atmospheric circulation patterns. The high median time-resolution of 58 years allows the identification of five abrupt event-boundaries (i.e., main forest expansion and decline excursions) synchronous with the sharp stadial/interstadial (GS/GI) transitions within dating uncertainties. During Heinrich Stadial 3 (HS 3) we reconstruct more open and dry conditions, compared to the other GS, with a dominant regional scale fire signal. Linkages between local fires and climate-driven fuel changes resulted in high-magnitude fire peaks close to GI/GS boundaries, even exacerbated by local peatland conditions. Finally, palaeoecological data from the HS 3 interval unveiled an internal variability suggesting a peak between 30,425 and 29,772 cal BP (2σ error) which matches more depleted δ 18 O values in alpine speleothems. We hypothesise that this signal, broadly resembling that of other mid-latitudes proxies, may be attributed to the southward shift of the Northern Hemisphere storm tracks and the associated delayed iceberg discharge events as documented during other HS.

The development of personalized therapies for ovarian carcinoma patients is still hampered by several limitations, mainly the difficulty of predicting patients' responses to chemotherapy in tumor cells isolated from peritoneal fluids. The main reason for the low predictive power of in vitro assays is related to the modification of the cancer cells' phenotype induced by the culture conditions, which results in changes to the activation state and drug sensitivity of tumor cells compared to their in vivo properties. We have defined the optimal culture conditions to set up a prognostic test to predict high-grade serous ovarian carcinoma (HGSOC) patients' responses to platinum chemotherapy. We evaluated the effects of hyaluronic acid (HA) and fibronectin matrices and the contribution of freezing/thawing processes to the cell response to platinum-based treatment, collecting spheroids from the ascitic fluids of 13 patients with stage II or III HGSOC. Our findings indicated that an efficient model used to generate predictive data for in vivo sensitivity to platinum is culturing fresh spheroids on HA, avoiding the use of previously frozen primary tumor cells. The establishment of this easy, reproducible and standardized testing method can significantly contribute to an improvement in therapeutic effectiveness, thus bringing the prospect of personalized therapy closer for ovarian carcinoma patients.

Gold nanomaterials hold great potential for biomedical applications. While this field is evolving rapidly, little attention has been paid to precise nanoparticle design and functionalization. Here, we show that when using proteins as targeting moieties, it is fundamental to immobilize them directionally to preserve their biological activity. Using full-length leptin as a case study, we have developed two alternative conjugation strategies for protein immobilization based on either a site-selective or a nonselective derivatization approach. We show that only nanoparticles with leptin immobilized site-selectively fully retain the ability to interact with the cognate leptin receptor. These results demonstrate the importance of a specified molecular design when preparing nanoparticles labeled with proteins.

An alpine ice core, extracted from the Adamello glacier (Central Italian Alps), was analyzed in its entire length through low background γ-spectroscopy, for the detection of 137 Cs. Our results show that in glacier ice 137 Cs is tightly bound to insoluble particulate matter inside the ice core, and it is therefore possible to restrict γ-spectroscopy analysis to particulate matter only. We show how the sensibility of the detection limit can be improved by almost one order of magnitude by using a well-type detector instead of a coaxial one. Hypothesis on the dating of some radioactive layers are also hereby presented., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

We analysed the spatial and temporal distribution of a selection of pesticides in Alpine glaciers used on the Po Plain in Northern Italy, near the Alps. By analysing a 102-m ice core taken from the Lys Glacier (Monte Rosa massif, Italy), we highlight historical contamination from the insecticide chlorpyrifos and the herbicide terbuthylazine, confirming the role of alpine glaciers as temporal sinks. In addition, we collected meltwater samples from six glaciers distributed along the Alpine Arc during the summer of 2016, which showed widespread contamination by pesticides. Overall, chlorpyrifos and terbuthylazine dominated the contaminant fingerprint of all of the studied glaciers, with contamination peaks occurring at the beginning of the melting season. This highlights the importance of the medium-range atmospheric transport of these pesticides in connection with agricultural practices in the areas beneath the Italian Alps, where they are widely applied. The release of pesticides in meltwater can lead to potential risks to the aquatic ecosystems of headwater streams, as we demonstrate for chlorpyrifos. This suggests that the medium-range atmospheric transport of pesticides should be considered as part of regulations to protect the water quality of these pristine environments., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Effective and selective targeting of the α V β 3 integrin subtype is of high relevance in cancer research for the development of therapeutic systems with improved efficacy and of diagnostic imaging probes. We report here a new class of highly selective, α V β 3 -targeted gold nanoparticles (AuNPs), which carry cyclic 4-aminoproline-RGD semipeptides (cAmpRGD) as the targeting moiety immobilized at low surface density on the poly(ethylene glycol) (PEG)-based nanoparticle coating. We show that these nanoparticles are potent inhibitors of the integrin-mediated melanoma tumor cell adhesion to vitronectin and are selectively internalized via receptor-mediated endocytosis. Furthermore, we have developed bifunctional cAmpRGD-functionalized AuNPs by conjugation of a fluorophore (FAM or TAMRA) to a separate set of reactive groups on the PEG-based coating. These bifunctional AuNPs not only recapitulate the binding properties of cAmpRGD-AuNPs but also can be visualized via confocal laser microscopy, allowing direct observation of nanoparticle internalization. The peculiar molecular design of these nanoparticles and their precisely defined architecture at the molecular level accounts for their selective integrin binding with very low nonspecific background., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Cryoconite, the typical sediment found on the surface of glaciers, is mainly known in relation to its role in glacial microbiology and in altering the glacier albedo. But if these aspects are relatively well addressed, the same cannot be said about the geochemical properties of cryoconite and the possible interactions with glacial and peri-glacial environment. Current glacier retreat is responsible for the secondary emission of species deposited in high-altitude regions in the last decades. The role played by cryoconite in relation to such novel geochemical fluxes is largely unknown. Few and scarce observations suggest that it could interact with these processes, accumulating specific substances, but why, how and to what extent remain open questions. Through a multi-disciplinary approach we tried to shed lights. Results reveal that the peculiar composition of cryoconite is responsible for an extreme accumulation capability of this sediment, in particular for some, specific, anthropogenic substances.

We analyzed the chronologies of cellulose stable isotopes (δ 13 C and δ 18 O) and tree-ring widths from European larch (Larix decidua) in a high-altitude site (2190ma.s.l.) at the bottom of a glacial valley in the Italian Alps, and investigated their dependence on monthly meteorological variables and δ 18 O precipitation values. The δ 18 O of tree-ring cellulose appears to be strongly driven by the δ 18 O of winter snowfall (November to March), which suggests that larch trees mostly use the snow-melt water of the previous winter during the growing season. This water, which also comes from the slope streams and from the underground flow of nearby steep slopes, infiltrates the soil in the valley bottom. The tree-ring cellulose δ 18 O values were also found to be influenced by the August precipitation δ 18 O and mean temperature. The associated regression model shows that the δ 18 O chronology from the tree rings explains up to 34% of the variance in the winter precipitation δ 18 O record, demonstrating the potential for reconstructing the δ 18 O isotopic composition of past winter precipitation in the study region. Unlike most other tree-ring studies that focus on growing season signals, in our study the summer signal was small and the winter signal dominant due to the special conditions of the glacial valley. Site topography, geomorphology and soil characteristics in particular influence the stable isotope signal in tree-ring cellulose., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Mineral dust aerosol (dust) is widely recognized as a fundamental component of the climate system and is closely coupled with glacial-interglacial climate oscillations of the Quaternary period. However, the direct impact of dust on the energy balance of the Earth system remains poorly quantified, mainly because of uncertainties in dust radiative properties, which vary greatly over space and time. Here we provide the first direct measurements of the aerosol optical thickness of dust particles windblown to central East Antarctica (Dome C) during the last glacial maximum (LGM) and the Holocene. By applying the Single Particle Extinction and Scattering (SPES) technique and imposing preferential orientation to particles, we derive information on shape from samples of a few thousands of particles. These results highlight that clear shape variations occurring within a few years are hidden to routine measurement techniques. With this novel measurement method the optical properties of airborne dust can be directly measured from ice core samples, and can be used as input into climate model simulations. Based on simulations with an Earth System Model we suggest an effect of particle non-sphericity on dust aerosol optical depth (AOD) of about 30% compared to spheres, and differences in the order of ~10% when considering different combinations of particles shapes.

Dust found in polar ice core samples present extremely low concentrations, in addition the availability of such samples is usually strictly limited. For these reasons the chemical and physical analysis of polar ice cores is an analytical challenge. In this work a new method based on low background instrumental neutron activation analysis (LB-INAA) for the multi-elemental characterization of the insoluble fraction of dust from polar ice cores is presented. Thanks to an accurate selection of the most proper materials and procedures it was possible to reach unprecedented analytical performances, suitable for ice core analyses. The method was applied to Antarctic ice core samples. Five samples of atmospheric dust (μg size) from ice sections of the Antarctic Talos Dome ice core were prepared and analyzed. A set of 37 elements was quantified, spanning from all the major elements (Na, Mg, Al, Si, K, Ca, Ti, Mn and Fe) to trace ones, including 10 (La, Ce, Nd, Sm, Eu, Tb, Ho, Tm, Yb and Lu) of the 14 natural occurring lanthanides. The detection limits are in the range of 10(-13)-10(-6) g, improving previous results of 1-3 orders of magnitude depending on the element; uncertainties lies between 4% and 60%., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: Intrauterine growth restriction (IUGR) is characterized by chronic nutrient deprivation and hypoxemia that alters the autonomous nervous system regulation of fetal heart rate variability (fHRV). Phase-rectified signal averaging (PRSA) is a new algorithm capable to identify periodic and quasi-periodic patterns of HR, and which is used to quantify the average acceleration and deceleration capacity (AC/DC) of the heart. The computation of AC/DC depends on the parameters T and s, which we set so that s=T. T and s determine the periodicities that can be detected (the larger T the smaller the frequency of oscillations for which the method is most sensitive). The aim of the study was to evaluate the influence of the parameter T on PRSA computation, based on trans-abdominally acquired fetal ECG (ta-fECG), in early IUGR (<34 weeks of gestation) at two different gestational age epochs., Study Design: AC/DC were calculated for different T values (1÷45) on fetal RR intervals derived from ta-fECG in 22 IUGR and in 37 appropriate for gestational age (AGA) fetuses matched for gestational age, in two gestational age epochs: very preterm group (≥26÷<30 weeks), and preterm group (≥30÷<34 weeks), respectively., Results: AC/DC were significantly lower in IUGR than in AGA fetuses for all T≥5 values (p<0.05). The best area under the receiver operating characteristic curve (AUC) in identifying IUGR at time of recording was observed for T9 [AUC AC-T9 0.87, 95% confidence interval (CI) 0.77-0.96; and AUC DC-T9 0.89, 95% CI 0.81-0.98), and in range of T 7÷15. In the same T interval, AC/DC were significantly lower in very preterm than in preterm IUGR group (p<0.05), while there were no differences in AGA fetuses at two gestational age epochs (p>0.05), respectively. The AUCs of AC-T9 and DC-T9 significantly outperformed that obtained by short-term variation (AUC 0.77, 95% CI 0.65-0.90; p=0.009 and p=0.003, respectively)., Conclusions: Our study shows that within the range of T parameter 1÷45, T=9 proved to be the best value to discriminate the AC and DC of the fetal heart rate of IUGR from AGA fetuses prior to 34 weeks of gestation. These significant differences are emphasized in very preterm gestational age epochs., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Curcumin (CR) is a natural polyphenol with antioxidative, anti-inflammatory, and anticancer properties but its therapeutic potential is substantially hindered by the rather low-water solubility and bioavailability. Thus, in this work, a new soluble inclusion complex of CR with sulfobutylether-β-cyclodextrin (SBE-β-CD) was prepared in solution and at the solid state using different preparation techniques and characterized by Fourier transform infrared, nuclear magnetic resonance, differential scanning calorimetry, scanning electron microscopy, phase solubility studies, and Job's plot method. Results clearly indicate that CR reacts with SBE-β-CD to form a host-guest complex with an apparent formation constant of 1455 M(-1) . Moreover, SBE-β-CD strongly increases water solubility of CR (from 0.56 to 102.78 μg/mL, at 25°C), and lyophilization method seems to be the best preparation technique to obtain the complex at the solid state. Finally, an in vitro test on a human hepatic cancer cell line (HepG-2) shows that complexation positively influences CR anticancer and antioxidant activity., (© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.)

To improve quantitative interpretation of ice core aeolian dust records, a systematic methodological comparison was made. This involved methods for water-insoluble particle counting (Coulter counter and laser-sensing particle detector), soluble ion analysis (ion chromatography and continuous flow analysis), elemental analysis (inductively coupled plasma mass spectroscopy at pH 1 and after full acid digestion), and water-insoluble elemental analysis (proton induced X-ray emission). Antarctic ice core samples covering the last deglaciation from the EPICA Dome C (EDC) and the EPICA Dronning Maud Land (EDML) cores were used. All methods correlate very well among each other, but the ratios of glacial age to Holocene concentrations, which are typically a factor approximately 100, differ between the methods by up to a factor of 2 with insoluble particles showing the largest variability. The recovery of ICP-MS measurements depends on the digestion method and is differentfor different elements and during different climatic periods. EDC and EDML samples have similar dust composition, which suggests a common dust source or a common mixture of sources for the two sites. The analyzed samples further reveal a change of dust composition during the last deglaciation.

Dust can affect the radiative balance of the atmosphere by absorbing or reflecting incoming solar radiation; it can also be a source of micronutrients, such as iron, to the ocean. It has been suggested that production, transport and deposition of dust is influenced by climatic changes on glacial-interglacial timescales. Here we present a high-resolution record of aeolian dust from the EPICA Dome C ice core in East Antarctica, which provides an undisturbed climate sequence over the past eight climatic cycles. We find that there is a significant correlation between dust flux and temperature records during glacial periods that is absent during interglacial periods. Our data suggest that dust flux is increasingly correlated with Antarctic temperature as the climate becomes colder. We interpret this as progressive coupling of the climates of Antarctic and lower latitudes. Limited changes in glacial-interglacial atmospheric transport time suggest that the sources and lifetime of dust are the main factors controlling the high glacial dust input. We propose that the observed approximately 25-fold increase in glacial dust flux over all eight glacial periods can be attributed to a strengthening of South American dust sources, together with a longer lifetime for atmospheric dust particles in the upper troposphere resulting from a reduced hydrological cycle during the ice ages.

A Flow Injection Analysis (FIA) spectrofluorimetric method for calcium determination in ice cores was optimised in order to achieve better analytical performances which would make it suitable for reliable calcium measurements at ppt level. The method here optimised is based on the formation of a fluorescent compound between Ca and Quin-2 in buffered environment. A careful evaluation of operative parameters (reagent concentration, buffer composition and concentration, pH), influence of interfering species possibly present in real samples and potential favourable effect of surfactant addition was carried out. The obtained detection limit is around 15 ppt, which is one order of magnitude lower than the most sensitive Flow Analysis method for Ca determination currently available in literature and reproducibility is better than 4% for Ca concentrations of 0.2 ppb. The method was validated through measurements performed in parallel with Ion Chromatography on 200 samples from an alpine ice core (Lys Glacier) revealing an excellent fit between the two chemical series. Calcium stratigraphy in Lys ice core was discussed in terms of seasonal pattern and occurrence of Saharan dust events.

Organochlorine pesticides (DDTs, HCHs, HCB) and selected PCBs were analyzed in samples from a firn core drilled on the Lys Glacier (4240 m above sea level, Monte Rosa Group, Italian Alps) in Summer 2000. The samples covered a relatively short time interval (from 1997 to 2000) and a seasonal detail breakdown was possible. A probable seasonal trend was observed only for gamma-HCH, a pesticide currently used in some European countries. For all other chemicals, a seasonal trend was not evident, and this supports the hypothesis of the prevailing role of long-range transport in comparison with local emissions for POP pollution in high mountains. The role of temperature on air-snow exchange has also been highlighted.

The Antarctic Vostok ice core provided compelling evidence of the nature of climate, and of climate feedbacks, over the past 420,000 years. Marine records suggest that the amplitude of climate variability was smaller before that time, but such records are often poorly resolved. Moreover, it is not possible to infer the abundance of greenhouse gases in the atmosphere from marine records. Here we report the recovery of a deep ice core from Dome C, Antarctica, that provides a climate record for the past 740,000 years. For the four most recent glacial cycles, the data agree well with the record from Vostok. The earlier period, between 740,000 and 430,000 years ago, was characterized by less pronounced warmth in interglacial periods in Antarctica, but a higher proportion of each cycle was spent in the warm mode. The transition from glacial to interglacial conditions about 430,000 years ago (Termination V) resembles the transition into the present interglacial period in terms of the magnitude of change in temperatures and greenhouse gases, but there are significant differences in the patterns of change. The interglacial stage following Termination V was exceptionally long--28,000 years compared to, for example, the 12,000 years recorded so far in the present interglacial period. Given the similarities between this earlier warm period and today, our results may imply that without human intervention, a climate similar to the present one would extend well into the future.

The expression of arginine-vasopressin (AVP) and galanin (GAL) was studied by immunohistochemistry and in situ hybridization in the hypothalamus of two species of African rodents. In the wild, these animals experience successive arid and wet seasons that alternately stimulate their antidiuretic and diuretic systems. In this study, animals were subjected to both standardized laboratory conditions and to eight days of water-restriction. Under both sets of conditions, AVP and GAL were detected in the supraoptic nucleus (SON), paraventricular nucleus (PVN), and median eminence (ME). AVP and GAL responses to water-restriction differed in the two species, as did behavioral adaptations to the hot-dry season. In Taterillus gracilis, AVP- and GAL-LI (like immunoreactivity) peptide and mRNA levels increased in the SON. AVP-LI peptide and mRNA levels increased in the PVN, whereas only AVP-LI peptide levels increased in the ME. Pituitary gland AVP pools were unchanged by water deprivation, whereas urinary AVP levels and osmolality increased. The AVP response is typical of that of desert rodents, favoring survival under conditions of water-restriction. In Steatomys caurinus, which estivates, AVP and GAL-LI peptide levels decreased in the hypothalamus, as they did in the laboratory rat. In the SON, AVP, and GAL mRNA levels increased, whereas, in the PVN, only AVP mRNA levels increased. Pituitary gland AVP levels decreased, whereas urinary AVP levels and osmolality increased. In both species, the changes in the amount of GAL-LI peptide appeared to be closely linked to changes in AVP levels, suggesting that this peptide is involved in the osmoregulatory response to water-restriction.

The effects of niperotidine, a novel histamine H2-receptor antagonist, on nocturnal gastric acid secretion in healthy volunteers, have been investigated. Twenty subjects were randomly assigned to the placebo (M:F = 7:3; Age 34 +/- SD3 yrs) or to the niperotidine-treated group (M:F = 7:3; Age: 37 +/- 6 yrs) in which 460 mg were administered at 22.00. Intragastric acidity was assessed by means of 24-hour pH-measurement (10.00-22.00) using sensitive antimony monocrystalline electrodes. The percentage of daytime gastric acidity (prandial and interprandial) was similar in both groups (median; interquartile range): placebo group 87.5; 69.5-90.1 vs niperotidine 85.8; 59-89.1. Niperotidine increased the intragastric pH during the period 22.00-10.00. The percentage of time above pH 4 was higher in the treated group (28.4; 14.8-50.7% vs 7.4; 1.4-10.7%; p less than 0.02). The duration of niperotidine action was 5 to 7 hours. The nocturnal pH frequency curve after niperotidine was shifted toward alkaline values with a decrease of acidity in the pH range 1-2 (p less than 0.04). We conclude that a bedtime dose of niperotidine inhibits nocturnal gastric acid secretion in healthy subjects.

The effect of a novel CCK-antagonist (lorglumide, CR 1409) was evaluated by "in vitro" tensiometric studies on 16 human (gallstone patients) and 12 guinea pig gallbladder smooth muscle strips. In the animal experiments, increasing doses of lorglumide (0.2-6.5 uM) caused a rightward shift of the dose-response curves of CCK-OP, with an increase of the ED50 from 8.2 nM +/- 1.62 SEM, n = 12; to 100 nM +/- 12, n = 4) without affecting the maximal effect (Emax). Schild plot gave an affinity constant of 7.19. In human gallbladders, the effect of lorglumide was also present (ED50 increased from 47 nM +/- 8 SEM, n = 16; to 300 nM +/- 10 SEM, n = 4) coexisting with a large inter-sample variation for CCK-OP ED50s and maximal contractions, most likely due to the histological changes of the wall in chronic cholecystitis. The affinity constant was similar to that found in animal experiments. We confirm the studies previously reported in animals on the existence of a competitive antagonism of lorglumide on CCK gallbladder receptors. Moreover, our results on gallbladders from gallstone patients show that lorglumide is a highly effective antagonist of CCK-induced contractions despite the presence of chronic cholecystitis. Our study might help for a better comprehension of the role of these new anti-CCK drugs in the treatment of biliary pain.

A fluorimetric method for the study of intracellular Ca++ metabolism in rat pancreatic acini is described. Following previous reports on the utilization of the new intracellularly trapped fluorescent dye fura2 in human lymphocytes, the authors point out the relevance of the cellular and fura2 concentration as critical issues for an accurate evaluation of Ca++ homeostasis. A dose-response curve to both carbamoylcholine and cholecystokinin is reported, demonstrating the ability of the cells to respond to hormonal stimulation with a transient Ca++ peak. The almost complete absence of noise in the recorded traces allow to carry out an evaluation of the intracellular mechanism related to Ca++ mobilization with a very high sensitivity.

Acid and alkaline phosphatases, esterases, and beta-glucuronidase were studied histochemically in the colon of a patient with familial polyposis in whom malignant changes had occurred. The acid hydrolases were found to be localized mainly in the supranuclear region of the cells of the epithelium of the normal mucosa. In the polyp epithelium these enzymes were found mainly in the basal areas of the epithelium at the junction between the latter and the lamina propria. In the cancer cells enzyme activity was decreased and distributed randomly. Alkaline phosphatase was present only in the capillaries in the normal and the polypmucosa. In the cancer tissue this enzyme was found in the capillaries, the smooth muscle cells, and the invading cells of epithelial origin.