Effect of lipid lowering therapy on LDL-S-homocysteinilation status in Chronic Kidney Disease patients

Chronic Kidney Disease (CKD) is currently recognized as an important global population health problem. Dyslipidemia associated with CKD contributes to the inflammatory response in renal failure. The dyslipidemia control through lipid lowering therapy is one of the targets for the treatment of CKD. The aim of this study is to evaluate the effect of hypolipidemic drugs on the LDL thiolation in proteinuric nefropatic patients during lipid lowering therapy. We enrolled thirty CKD patients randomized to receive three different hypolipidemic regimens: simvastatin alone (40 mg/day) or ezetimibe/ simvastatin combined therapy (10/20 or 10/40 mg/day). LMW thiols in their reduced and total form, oxidative stress indices as malondialdehyde and allantoin/uric acid ratio were evaluated. LDL thiolation decreased in all treated patients, but a greater efficacy was attained from a combined therapy with a higher simvastatin dose. In particular, in this patients group the reduction of apoB-Hcy was greater than 40%. The concomitant decrease of the oxidative stress indices during the therapy brings to the hypothesis that decreased levels of protein bound thiols may be a consequence of oxidative stress improvement. Therefore, among the several beneficial effects described for lipid lowering drugs we also propose their ability to reduce the quantity of LDL linked homocysteine thus decreasing not only LDL levels but also LDL atherogenicity

Plasma L-ergothioneine measurement by high-performance liquid chromatography and capillary electrophoresis after a pre-column derivatization with 5-iodoacetamidofluorescein (5-IAF) and fluorescence detection

Two sensitive and reproducible capillary electrophoresis and high-performance liquid chromatography-fluorescence procedures were established for quantitative determination of L-egothioneine in plasma. After derivatization of L-ergothioneine with 5-iodoacetamidofluorescein, the separation was carried out by HPLC on an ODS-2 C-18 sperisorb column by using a linear gradient elution and by HPCE on an uncoated fused silica capillary, 50 µm id, and 60 cm length. The methods were validated and found to be linear in the range of 0.3 to 10 µmol/l. The limit of quantification was 0.27 µmol/l for HPCE and 0.15 µmol/l for HPLC. The variations for intra- and inter-assay precision were around 6 RSD%, and the mean recovery accuracy close to 100% (96.11%)

Biological markers of sex-based differences in major depressive disorder and in antidepressant response

Major depressive disorder (MDD) presents different clinical features in women and men, with women being more affected and responding differently to antidepressant treatment. Specific molecular mechanisms underlying these differences are not well studied and this narrative review aims at providing an overview of the neurobiological features underlying sex-differences in biological systems involved in MDD pathophysiology and response to antidepressant treatment, focusing on human studies. The majority of the reviewed studies were performed through candidate gene approaches, focusing on biological systems involved in MDD pathophysiology, including the stress response, inflammatory and immune, monoaminergic, neurotrophic, gamma-aminobutyric acid and glutamatergic, and oxytocin systems. The influence of the endocrine system and sex-specific hormone effects are also discussed. Genome, epigenome and transcriptome-wide approaches are less frequently performed and most of these studies do not focus on sex-specific alterations, revealing a paucity of omics studies directed to unravel sex-based differences in MDD. Few studies about sex-related differences in antidepressant treatment response have been conducted, mostly involving the inflammatory system, with less evidence on the monoaminergic system and sparse evidence in omics approaches. Our review covers the importance of accounting for sex-differences in research, optimizing patient stratification for a more precise diagnostic and individualized treatment for women and men

Association between Human Plasma Chondroitin Sulfate Isomers and Carotid Atherosclerotic Plaques

Several studies have evidenced variations in plasma glycosaminoglycans content in physiological and pathological conditions. In normal human plasma GAGs are present mainly as undersulfated chondroitin sulfate (CS). The aim of the present study was to evaluate possible correlations between plasma CS level/structure and the presence/typology of carotid atherosclerotic lesion. Plasma CS was purified from 46 control subjects and 47 patients undergoing carotid endarterectomy showing either a soft or a hard plaque. The concentration and structural characteristics of plasma CS were assessed by capillary electrophoresis of constituent unsaturated fluorophore-labeled disaccharides. Results showed that the concentration of total CS isomers was increased by 21.4% (P < 0.01) in plasma of patients, due to a significant increase of undersulfated CS. Consequently, in patients the plasma CS charge density was significantly reduced with respect to that of controls. After sorting for plaque typology, we found that patients with soft plaques and those with hard ones differently contribute to the observed changes. In plasma from patients with soft plaques, the increase in CS content was not associated with modifications of its sulfation pattern. On the contrary, the presence of hard plaques was associated with CS sulfation pattern modifications in presence of quite normal total CS isomers levels. These results suggest that the plasma CS content and structure could be related to the presence and the typology of atherosclerotic plaque and could provide a useful diagnostic tool, as well as information on the molecular mechanisms responsible for plaque instability

Asymptomatic and symptomatic deep venous thrombosis in hospitalized acutely ill medical patients: risk factors and therapeutic implications

Background Acutely ill medical patients experience deep venous thrombosis (DVT) during the hospitalization, however the time course of DVT is still unclear. Objectives To evaluate risk factors in acutely ill hospitalized medical patients for proximal asymptomatic DVT (ADVT) and symptomatic DVT (SDVT) at admission and discharge. Patients/Methods In this prospective observational study, consecutive acutely ill medical patients (hospitalized mainly for acute medical disease as infections, neoplasm, anemia, heart failure) underwent compression ultrasonography (CUS) of proximal lower limb veins within 48 h from admission and at discharge to diagnose ADVT and SDVT. Covid-19 patients, anticoagulant therapy, surgical procedures, acute SDVT, and acute pulmonary embolism, were exclusion criteria. Biographical characteristics at hospitalization, D-Dimer (assessed by ELISA)) and DD-improve score. Results Of 2,100 patients (1002 females, 998 males, age 71 +/- 16 years) 58 (2.7%) had proximal ADVT at admission. Logistic regression analysis showed that age, and active cancer were independently associated with ADVT at admission. The median length of hospitalization was 10 days [interquartile range: 6-15]. During the hospital stay, 6 patients (0.3%) with a negative CUS at admission experienced DVT (2 SDVT and 4 ADVT). In the subgroup of patients (n = 1118), in whom D-dimer was measured at admission, D-Dimer and IMPROVE-DD score were associated with ADVT at admission (n = 37) and with all DVT (n = 42) at discharge. ROC curve defined an IMPROVE-DD score of 2.5 as the optimal cut-off for discriminating patients with and without thrombotic events. Conclusions We provide evidence of early development of ADVT in unselected acutely ill medical patients suggesting the need of investigating patients by CUS immediately after hospital admission (within 48 h). Advanced age, active cancer, known thrombophilia and increased IMPROVE-DD score may identify patients at risk. The benefit of anticoagulation needs to be investigated in patients with these specific risk factors and negative CUS at admission

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p &lt; 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

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 &gt; 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

Plant–environment interactions through a functional traits perspective: a review of Italian studies

Italy is among the European countries with the greatest plant diversity due to both a great environmental heterogeneity and a long history of man–environment interactions. Trait-based approaches to ecological studies have developed greatly over recent decades worldwide, although several issues concerning the relationships between plant functional traits and the environment still lack sufficient empirical evaluation. To draw insights on the association between plant functional traits and direct and indirect human and natural pressures on the environmental drivers, this article summarizes the existing knowledge on this topic by reviewing the results of studies performed in Italy adopting a functional trait approach on vascular plants, bryophytes and lichens. Although we recorded trait measurements for 1418 taxa, our review highlighted some major gaps in plant traits knowledge: Mediterranean ecosystems are poorly represented; traits related to belowground organs are still overlooked; traits measurements for bryophytes and lichens are lacking. Finally, intraspecific variation has been little studied at community level so far. We conclude by highlighting the need for approaches evaluating trait–environment relationship at large spatial and temporal scales and the need of a more effective contribution to online databases to tie more firmly Italian researchers to international scientific networks on plant traits

The Role of Personality in Shaping Neural Processes Associated with Theory of Mind

Personality accounts for a significant amount of individual differences in people’s academic and life outcomes. In my dissertation, I focused on agreeableness, a personality trait from the Five Factor Model describing individual differences in altruism, empathy, and Theory of Mind (ToM) (Allen et al., 2017). Thus, my primary aim was to investigate whether and how agreeableness might modulate social and emotional processes associated with ToM in the general population and in young adults with Autism Spectrum Disorder (ASD) without language and intellectual impairments. All these aspects are introduced in Chapter 1 of my thesis, while the original experimental studies are described in the following Chapters (2-5). In Chapter 2, I report an fMRI study (Study 1) exploring whether neural variations during social content encoding are related to differences in agreeableness by assessing the degree of similarity between patterns of activation for social and non-social content across individuals. Results suggested that more agreeable individuals encode social and non-social information more distinctively compared with less agreeable individuals, whose encoding of the two contents is more similar in the dorso-medial prefrontal cortex (dmPFC), a brain region typically linked with ToM abilities (Saxe and Baron-Cohen, 2006). This result suggests that individual differences in agreeableness are associated with differences in processing social information. Based on this finding, I developed three studies that aimed at characterizing the neural correlates of agreeableness and different aspects of ToM by means of electroencephalography (EEG). This approach allowed me to identify at which stage of the neural processing agreeableness kicks in, in order to distinguish the impact on early, perceptual processes from slower, inferential processing. Since ToM involves distinct processes, I first set out to investigate the social (Study 2) and emotional dimensions (Study 3) separately; then I examined the same processes within a group of individuals within the autism spectrum (Study 4). Thus Chapter 3 contains Study 2 in which I assessed the impact of agreeableness on social interaction perception. Results revealed agreeableness allows a deeper processing of social stimuli compared to non-social ones, mainly in fronto-parietal areas. This relatively early effect in the whole sample and in females was more massive and extensive in males and translated into behavior as a tendency towards a better ability to discriminate social interactions. Chapter 4 contains Study 3 in which I investigated the modulation of agreeableness on the decoding of emotional cues by means of two tasks with different degrees of complexity spanning from the perception of basic emotional actions to the recognition of complex mental states. Results showed that agreeableness affects brain’s activity only during mental state decoding in male participants, mainly involving the ventro-mPFC, while in females this modulation seems to be negligible. Study 4, in Chapter 5, investigates the personality of young adults with ASD without language and intellectual impairment, and whether agreeableness might differentially modulate the same neural processes investigated in the previous two EEG studies in this population. This investigation underscored that while young adults with this diagnosis may exhibit lower scores in all the five traits, they do not uniformly fall into the extreme ends of all personality dimensions. Results further highlighted the role of agreeableness in shaping socio-emotional processing, particularly in the context of ToM tasks. Notably, ASD individuals showcased a capacity for compensatory mechanisms, achieving behavioral performance akin to less agreeable healthy controls despite differences in neural responses. Overall, the findings of my thesis advance our understanding of the neural determinants of agreeableness and its significance in the social domain. This has potential implications for clinical interventions by tailoring treatments to individual variations, thus enhancing effective therapeutic strategies. In the final Chapter 6, I contextualize these findings within the existing literature and I discuss their implications

Food olfactory cues reactivity in individuals with obesity and the contribution of alexithymia

Obesity has been associated with increased reward sensitivity to food stimuli, but a few studies have addressed this issue by using odors. This study investigated whether obesity is associated with increased liking and wanting of food odors and whether alexithymia, a psychological construct characterized by diminished affective abilities, contributes to altered responsiveness to food. Liking and wanting for food and pleasant non-food odors were measured through explicit (self-report ratings) and implicit measures (heart rate and skin conductance) in 23 women with healthy weight (HW) and 20 women with overweight/obesity (OW/OB). Differently from the HW group, the OW/OB group explicitly liked food odors less than non-food odors; but, at the implicit level, there were no differences in heart rate response for both types of odors, indicating that they were equally liked. Moreover, at variance with the HW group, the OW/OB group did not exhibit increased skin conductance response for food compared to nonfood odors. Alexithymia was associated with increased implicit liking and explicit wanting of food odors, in particular in the HW group. These findings show that obesity is characterized by high levels of implicit food liking and low levels of implicit food wanting. Moreover, both affective and motivational responses to food reward seem to be affected by alexithymia, which should be taken into account by studies evaluating the effect of cue exposure intervention for obesity treatment