Effect of maternal separation on ethanol drinking and acute stress: involvement of ethanol consumption during pregnancy

It is known that stressful events during gestational and postnatal period are crucial for the development of psychopathologies in adulthood. It is widely accepted that prenatal ethanol exposure during late pregnancy is one of the most consisted method that leads to alcohol abuse behavior in young and/or adults later in life. In order to evaluate the interaction between prenatal ethanol exposure and early life stress, a group of pregnant rats (EtOH) was treated intra-gastrically with 1g/Kg of ethanol solution later in gestation from 17 to GD 20. The offspring were then subjected to daily maternal separation (MS) for 3hs from PND 3 until PND 15. Since ethanol treatment and maternal separation stimulates the HPA axis response we evaluate whether the exposure to alcohol in this delicate perinatal could affect HPA axis response to acute foot-shock stress as well as maternal behavior, reflecting in the quality of maternal care. Our results show that the association of the two stressors (EtOH and MS) leads to a significant decrease in the CTS and AP plasma level. Furthermore, EtOH-MS group shows a greater acute foot-shockmediated increase of CTS and AP plasma levels compared to EtOH-NMS group. In agreement with this hormonal response, elevated plus maze test revealed anxiety-like behavior of the EtOH-MS group respect to EtOH-NMS counterpart. In addition, our data showed that prenatal ethanol treatment failed to induce changes in maternal care behavior. One goal of our study was to establish whether the association of two stressors (prenatal ethanol treatment and early maternal separation) could lead to changes in alcohol consumption preference in adolescent and adult male offspring. We used the Ascending Ethanol Paradigm (Martinetti et al., 2006), that consist in giving ascending concentrations (from 0.01% to 20%) of ethanol both in adolescence and in adulthood. Our data show that there are no differences among the four experimental groups in terms of preference toward ethanol consumption. However, the VEH-MS show a clear behavior preference toward 0.1-1% range of ethanol concentrations. Overall, these results suggest that stressful experiences during pregnancy and childhood may change the acute stress-responsiveness of HPA axis in adult rats. Furthermore, there is not evident interaction between pre and postnatal stress regarding the effect on drinking behavior. Furthermore, these animals probably came out from two closely stressful events differently from adults that have had much more time to recovery from each other. This could partially explain the lack of difference in ethanol consumption attitude. Further studies may help to better understand some molecular mechanisms underlying these observed differences between adult and adolescent offspring subjected to stress early in life

Isolation rearing reduces neuronal excitability in dentate gyrus granule cells of adolescent C57BL/6J mice: role of gabaergic tonic currents and neurosteroids

Early-life exposure to stress, by impacting on a brain still under development, is considered a critical factor for the increased vulnerability to psychiatric disorders and abuse of psychotropic substances during adulthood. As previously reported, rearing C57BL/6J weanling mice in social isolation (SI) from their peers for several weeks, a model of prolonged stress, is associated with a decreased plasma and brain levels of neuroactive steroids such as 3α,5α-THP, with a parallel up-regulation of extrasynaptic GABAA receptors (GABAAR) in dentate gyrus (DG) granule cells compared to group-housed (GH) mice. In the present study, together with the SI-induced decrease in plasma concentration of both progesterone and 3a,5a-THP, and an increase in THIP-stimulated GABAergic tonic currents, patch-clamp analysis of DG granule cells revealed a significant decrease in membrane input resistance and action potential (AP) firing rate, in SI compared to GH mice, suggesting that SI exerts an inhibitory action on neuronal excitability of these neurons. Voltage-clamp recordings of glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs) revealed a SI-associated decrease in frequency as well as a shift from paired-pulse (PP) depression to PP facilitation (PPF) of evoked EPSCs, indicative of a reduced probability of glutamate release. Daily administration of progesterone during isolation reverted the changes in plasma 3α,5α-THP as well as in GABAergic tonic currents and neuronal excitability caused by SI, but it had only a limited effect on the changes in the probability of presynaptic glutamate release. Overall, the results obtained in this work, together with those previously published, indicate that exposure of mice to SI during adolescence reduces neuronal excitability of DG granule cells, an effect that may be linked to the increased GABAergic tonic currents as a consequence of the sustained decrease in plasma and hippocampal levels of neurosteroids. All these changes may be consistent with cognitive deficits observed in animals exposed to such type of prolonged stres

Can the development and autolysis of lactic acid bacteria influence the cheese volatile fraction? The case of Grana Padano

In this study, the relationship between the dynamics of the growth and lysis of lactic acid bacteria in Grana Padano cheese and the formation of the volatile flavor compounds during cheese ripening was investigated. The microbial dynamics of Grana Padano cheeses thatwere produced in two different dairies were followed during ripening. The total and cultivable lactic microflora, community composition as determined by length heterogeneity- PCR (LH-PCR), and extent of bacterial lysis using an intracellular enzymatic activity assaywere compared among cheeses after 2, 6 and 13 months of ripening in two dairies. The evolution of whole and lysed microbiota was different between the two dairies. In dairy 2, the number of total cells was higher than that in dairy 1 in all samples, and the number of cells that lysed during ripening was lower. In addition, at the beginning of ripening (2 months), the community structure of the cheese from dairy 2 was more complex and was composed of starter lactic acid bacteria (Lactobacillus helveticus and Lactobacillus delbrueckii) and NSLAB, possibly arising fromraw milk, including Lactobacillus rhamnosus/Lactobacillus casei and Pediococcus acidilactici. On the other hand, the cheese from dairy 1 that ripened for 2 months was mainly composed of the SLAB L. helveticus and L. delbrueckii. An evaluation of the free-DNA fraction through LH-PCR identified those species that had a high degree of lysis. Data on the dynamics of bacterial growth and lysis were evaluated with respect to the volatile profile and the organic acid content of the two cheeses after 13 months of ripening, producing very different results. Cheese from dairy 1 showed a higher content of free fatty acids, particularly those deriving from milk fat lipolysis, benzaldehyde and organic acids, such as pGlu and citric. In contrast, cheese from dairy 2 had a greater amount of ketones, alcohols, hydrocarbons, acetic acid and propionic acid. Based on these results, we can conclude that in the first cheese, the intracellular enzymes thatwere released fromlysiswere mainly involved in aromaformation,whereas in the second cheese, the greater complexity of volatile compounds may be associated with its more complex microbial composition caused from SLAB lysis and NSLAB (mainly L. rhamnosus/L. casei) growth during ripening

Tobacco Smoking Is a Strong Predictor of Failure of Conservative Treatment in Hinchey IIa and IIb Acute Diverticulitis-A Retrospective Single-Center Cohort Study

Background and Objectives: Therapeutic management of patients with complicated acute diverticulitis remains debatable. The primary objective of this study is to identify predictive factors for the failure of conservative treatment of Hinchey IIa and IIb diverticular abscesses. Materials and Methods: This is a retrospective cohort study that included patients hospitalized from 1 January 2014 to 31 December 2022 at the Emergency Surgery Department of the Cagliari University Hospital (Italy), diagnosed with acute diverticulitis complicated by Hinchey grade IIa and IIb abscesses. The collected variables included the patient's baseline characteristics, clinical variables on hospital admission, abscess characteristics at the contrast-enhanced CT scan, clinical outcomes of the conservative therapy, and follow-up results. Univariable and multivariable logistic regression models were used to identify prognostic factors of conservative treatment failure and success. Results: Two hundred and fifty-two patients diagnosed with acute diverticulitis were identified from the database search, and once the selection criteria were applied, 71 patients were considered eligible. Conservative treatment failed in 25 cases (35.2%). Univariable analysis showed that tobacco smoking was the most significant predictor of failure of conservative treatment (p = 0.007, OR 7.33, 95%CI 1.55; 34.70). Age (p = 0.056, MD 6.96, 95%CI -0.18; 0.99), alcohol drinking (p = 0.071, OR 4.770, 95%CI 0.79; 28.70), platelets level (p = 0.087, MD -32.11, 95%CI -0.93; 0.06), Hinchey stage IIa/IIb (p = 0.081, OR 0.376, 95%CI 0.12; 1.11), the presence of retroperitoneal air bubbles (p = 0.025, OR 13.300, 95%CI 1.61; 291.0), and the presence of extraluminal free air at a distance (p = 0.043, OR 4.480, 95%CI 1.96; 20.91) were the other variables possibly associated with the risk of failure. In the multivariable logistic regression analysis, only tobacco smoking was confirmed to be an independent predictor of conservative treatment failure (p = 0.006; adjusted OR 32.693; 95%CI 2.69; 397.27). Conclusion: The role of tobacco smoking as a predictor of failure of conservative therapy of diverticular abscess scenarios highlights the importance of prevention and the necessity to reduce exposure to modifiable risk factors

Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6+/-9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; pPeer reviewe

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI