Characterization and Biological Activities of In Vitro Digested Olive Pomace Polyphenols Evaluated on Ex Vivo Human Immune Blood Cells.

Olive pomace (OP) represents one of the main by-products of olive oil production, which still contains high quantities of health-promoting bioactive compounds. In the present study, three batches of sun-dried OP were characterized for their profile in phenolic compounds (by HPLC-DAD) and in vitro antioxidant properties (ABTS, FRAP and DPPH assays) before (methanolic extracts) and after (aqueous extracts) their simulated in vitro digestion and dialysis. Phenolic profiles, and, accordingly, the antioxidant activities, showed significant differences among the three OP batches, and most compounds showed good bioaccessibility after simulated digestion. Based on these preliminary screenings, the best OP aqueous extract (OP-W) was further characterized for its peptide composition and subdivided into seven fractions (OP-F). The most promising OP-F (characterized for its metabolome) and OP-W samples were then assessed for their potential anti-inflammatory properties in ex vivo human peripheral mononuclear cells (PBMCs) triggered or not with lipopolysaccharide (LPS). The levels of 16 pro-and anti-inflammatory cytokines were measured in PBMC culture media by multiplex ELISA assay, whereas the gene expressions of interleukin-6 (IL-6), IL-10 and TNF-α were measured by real time RT-qPCR. Interestingly, OP-W and PO-F samples had a similar effect in reducing the expressions of IL-6 and TNF-α, but only OP-W was able to reduce the release of these inflammatory mediators, suggesting that the anti-inflammatory activity of OP-W is different from that of OP-F.

Easier Said Than Done: The Challenge to Teach "Personal Recovery" to Mental Health Professionals Through a Short, Targeted and Structured Training Programme.

This study assesses the effectiveness of our short Personal Recovery Training Program (PRTP) for mental health professionals. Fifty-two healthcare professionals from Italian mental health services and forty students in psychiatric rehabilitation completed the Recovery Knowledge Inventory (RKI) pre- and post-training, divided into two groups: the PRTP (N = 45) and the Family Psychoeducational Training Program (FPTP; N = 47). Participants' understanding of personal recovery improved more significantly for those in the PRTP than for those in the FPTP group in two domains, "Roles and responsibilities" and "Non-linearity of the recovery process"; the FPTP group showed a significant improvement in the "Role of self-definition and peers in recovery" domain. Two consumers were involved in the PRTP and represented a resource to help participants understand the personal recovery process. Our findings indicate that a brief PRTP supported by consumers can improve staff and students' recovery orientation. The translation of the training into clinical practice remains unevaluated.

Bariatric surgery restores visual cortical plasticity in nondiabetic subjects with obesity.

BACKGROUND/OBJECTIVES: Obesity leads to changes in synaptic plasticity. We aimed at investigating the impact of bariatric surgery (RYGB) on visual neural plasticity (NP) and its relationship with the main gut peptides, leptin, and brain-derived neurotrophic factor (BDNF). SUBJECTS/METHODS: NP was assessed testing binocular rivalry before and after 2 h of monocular deprivation (index of visual brain plasticity) in 15 subjects with obesity (age 42.3 ± 9.8 years; BMI 46.1 ± 4.9 kg/m2) before and after RYGB. Gut peptides, leptin, and BDNF were obtained at baseline and 6 months after surgery in 13 subjects. RESULTS: A significant reduction in BMI (p < 0.001 vs. baseline) and a significant increase of disposition index (DI, p = 0.02 vs baseline) were observed after RYGB. Total and active GLP-1 release in response to glucose ingestion significantly increased after RYGB, while no changes occurred in VIP, GIP, and BDNF levels. Fasting leptin concentration was lower after RYGB (p = 0.001 vs. baseline). Following RYGB, NP was progressively restored (p < 0.002). NP was correlated with DI and fasting glucose at baseline (r = 0.75, p = 0.01; r = -0.7, p = 0.02; respectively), but not with BMI. A positive correlation between post-pre-RYGB changes in AUCactive GLP-1 and NP was observed (r = 0.70, p < 0.01). Leptin was inversely correlated with NP 6 months after surgery (r = -0.63, p = 0.02). No correlation was observed between GIP, VIP, BDNF, and NP. CONCLUSIONS: Visual plasticity is altered in subjects with obesity, and it can be restored after RYGB. The improvement may be mediated by amelioration of insulin sensitivity, increased GLP-1 levels, and reduced leptin levels.

Distance education during COVID 19: an Italian survey on the university teachers' perspectives and their emotional conditions.

BACKGROUND: Following the COVID-19 pandemic, distance education (DE) replaced traditional "face-to-face" teaching and has become the main method of teaching. The aim of this study was to 1) evaluate the impact of DE by teachers in our department during the second semester of the 2019-20 academic year following the March-May 2020 Italian national lockdown and 2) evaluate the relationship between DE and the emotional well-being of teachers during the period of home confinement. METHODS: Ninety-seven university teachers (51.5% women; most represented age group 60-69 years range, 40.2%) responded to an anonymous online cross-sectional survey between July 15 - September 30, 2020, on the advantages and disadvantages of DE, developed by one online teacher focus group. The emotional conditions were assessed by a short version of the Beck Depression Inventory-II (BDI-II). The internal consistency reliability survey and the 10-item BDI-II were measured by Cronbach's alpha. A correlation analysis (r-Pearson) was conducted between the overall evaluation of the experience of DE and the variables included in the study. RESULTS: Teachers reported difficulties in technical aspects, and in psychological factors, as the discomfort of "speaking in the void" (64.7%). The absence of "face-to-face" eye contact with the students was complained by 81% of teachers. Significant impairments in sleep patterns and loss of energy were reported, with female teachers having greater difficulty concentrating than their male colleagues. A quarter of teachers showed depressive symptoms of varying severity. The most satisfied teachers were those most stimulated by DE (r = 0.752, p < 0.000), who showed a lower impact of depressive symptoms (r = - 0.289, p = 0.005). The teaching load in hours influenced the perception of disadvantages (r = 0.214, p = 0.035) and contributed to a lower appreciation of the challenges of DE. The more significant the manifestation of depressive symptoms during the lockdown was, the greater the subjective recovery of a good emotional condition once the domestic confinement was over (r = 0.344, p = 0.001), despite maintaining DE. CONCLUSIONS: Our study highlights the impact of technical, didactic, and psychological difficulties of DE, reported by our teachers. The appreciation of their new learning promoted by DE seemed related to better emotional well-being of university teachers accepting this "challenge" in their important role in the high-education system, influencing good learning and promoting students' professional success.

Salivary Proteome Changes in Response to Acute Psychological Stress Due to an Oral Exam Simulation in University Students: Effect of an Olfactory Stimulus.

The autonomic nervous system (ANS) plays a crucial role both in acute and chronic psychological stress eliciting changes in many local and systemic physiological and biochemical processes. Salivary secretion is also regulated by ANS. In this study, we explored salivary proteome changes produced in thirty-eight University students by a test stress, which simulated an oral exam. Students underwent a relaxation phase followed by the stress test during which an electrocardiogram was recorded. To evaluate the effect of an olfactory stimulus, half of the students were exposed to a pleasant odor diffused in the room throughout the whole session. Saliva samples were collected after the relaxation phase (T0) and the stress test (T1). State anxiety was also evaluated at T0 and T1. Salivary proteins were separated by two-dimensional electrophoresis, and patterns at different times were compared. Spots differentially expressed were trypsin digested and identified by mass spectrometry. Western blot analysis was used to validate proteomic results. Anxiety scores and heart rate changes indicated that the fake exam induced anxiety. Significant changes of α-amylase, polymeric immunoglobulin receptor (PIGR), and immunoglobulin α chain (IGHA) secretion were observed after the stress test was performed in the two conditions. Moreover, the presence of pleasant odor reduced the acute social stress affecting salivary proteome changes. Therefore, saliva proteomic analysis was a useful approach to evaluate the rapid responses associated to an acute stress test also highlighting known biomarkers.

Preclinical Development of FA5, a Novel AMP-Activated Protein Kinase (AMPK) Activator as an Innovative Drug for the Management of Bowel Inflammation.

Acadesine (ACA), a pharmacological activator of AMP-activated protein kinase (AMPK), showed a promising beneficial effect in a mouse model of colitis, indicating this drug as an alternative tool to manage IBDs. However, ACA displays some pharmacodynamic limitations precluding its therapeutical applications. Our study was aimed at evaluating the in vitro and in vivo effects of FA-5 (a novel direct AMPK activator synthesized in our laboratories) in an experimental model of colitis in rats. A set of experiments evaluated the ability of FA5 to activate AMPK and to compare the efficacy of FA5 with ACA in an experimental model of colitis. The effects of FA-5, ACA, or dexamethasone were tested in rats with 2,4-dinitrobenzenesulfonic acid (DNBS)-induced colitis to assess systemic and tissue inflammatory parameters. In in vitro experiments, FA5 induced phosphorylation, and thus the activation, of AMPK, contextually to the activation of SIRT-1. In vivo, FA5 counteracted the increase in spleen weight, improved the colon length, ameliorated macroscopic damage score, and reduced TNF and MDA tissue levels in DNBS-treated rats. Of note, FA-5 displayed an increased anti-inflammatory efficacy as compared with ACA. The novel AMPK activator FA-5 displays an improved anti-inflammatory efficacy representing a promising pharmacological tool against bowel inflammation.

Increase in endogenous glucose production with SGLT2 inhibition is attenuated in individuals who underwent kidney transplantation and bilateral native nephrectomy.

AIMS/HYPOTHESIS: The glucosuria induced by sodium-glucose cotransporter 2 (SGLT2) inhibition stimulates endogenous (hepatic) glucose production (EGP), blunting the decline in HbA1c. We hypothesised that, in response to glucosuria, a renal signal is generated and stimulates EGP. To examine the effect of acute administration of SGLT2 inhibitors on EGP, we studied non-diabetic individuals who had undergone renal transplant with and without removal of native kidneys. METHODS: This was a parallel, randomised, double-blind, placebo-controlled, single-centre study, designed to evaluate the effect of a single dose of dapagliflozin or placebo on EGP determined by stable-tracer technique. We recruited non-diabetic individuals who were 30-65 years old, with a BMI of 25-35 kg/m2 and stable body weight (±2 kg) over the preceding 3 months, and HbA1c <42 mmol/mol (6.0%). Participants had undergone renal transplant with and without removal of native kidneys and were on a stable dose of immunosuppressive medications. Participants received a single dose of dapagliflozin 10 mg or placebo on two separate days, at a 5- to 14-day interval, according to randomisation performed by our hospital pharmacy, which provided dapagliflozin and matching placebo, packaged in bulk bottles that were sequentially numbered. Both participants and investigators were blinded to group assignment. RESULTS: Twenty non-diabetic renal transplant patients (ten with residual native kidneys, ten with bilateral nephrectomy) participated in the study. Dapagliflozin induced greater glucosuria in individuals with residual native kidneys vs nephrectomised individuals (8.6 ± 1.1 vs 5.5 ± 0.5 g/6 h; p = 0.02; data not shown). During the 6 h study period, plasma glucose decreased only slightly and similarly in both groups, with no difference compared with placebo (data not shown). Following administration of placebo, there was a progressive time-related decline in EGP that was similar in both nephrectomised individuals and individuals with residual native kidneys. Following dapagliflozin administration, EGP declined in both groups, but the differences between the decrement in EGP with dapagliflozin and placebo in the group with bilateral nephrectomy (Δ = 1.11 ± 0.72 µmol min-1 kg-1) was significantly lower (p = 0.03) than in the residual native kidney group (Δ = 2.56 ± 0.33 µmol min-1 kg-1). In the population treated with dapagliflozin, urinary glucose excretion was correlated with EGP (r = 0.34, p < 0.05). Plasma insulin, C-peptide, glucagon, prehepatic insulin:glucagon ratio, lactate, alanine and pyruvate concentrations were similar following placebo and dapagliflozin treatment. ß-Hydroxybutyrate increased with dapagliflozin treatment in the residual native kidney group, while a small increase was observed only at 360 min in the nephrectomy group. Plasma adrenaline (epinephrine) did not change after dapagliflozin and placebo treatment in either group. Following dapagliflozin administration, plasma noradrenaline (norepinephrine) increased slightly in the residual native kidney group and decreased in the nephrectomy group. CONCLUSIONS/INTERPRETATION: In nephrectomised individuals, the hepatic compensatory response to acute SGLT2 inhibitor-induced glucosuria was attenuated, as compared with individuals with residual native kidneys, suggesting that SGLT2 inhibitor-mediated stimulation of hepatic glucose production via efferent renal nerves occurs in an attempt to compensate for the urinary glucose loss (i.e. a renal-hepatic axis). TRIAL REGISTRATION: ClinicalTrials.gov NCT03168295 FUNDING: This protocol was supported by Qatar National Research Fund (QNRF) Award No. NPRP 8-311-3-062 and NIH grant DK024092-38. Graphical abstract.

Effects of treatment with metformin and/or sitagliptin on beta-cell function and insulin resistance in prediabetic women with previous gestational diabetes.

AIM: To investigate the effect of sitagliptin (SITA) and metformin (MET) monotherapy as well as in combination (MET+SITA) on beta-cell function and insulin sensitivity in women with recent gestational diabetes (GDM) and impaired glucose regulation (IGR: impaired fasting glucose and/or impaired glucose tolerance). MATERIAL AND METHODS: Forty women were randomly assigned to receive SITA (100 mg qd), MET (850 mg bid) or MET+SITA (50 + 850 mg bid) for 16 weeks. A 75 g oral glucose tolerance test (OGTT) and +125 mg/dL hyperglycaemic clamp followed by 5 g i.v. L-arginine were performed at baseline and end of study. The primary outcome of the study was the mean change in arginine-stimulated insulin secretion rate during the hyperglycaemic clamp test from baseline to 16-week therapy. RESULTS: At week 16, body mass index declined in all groups (-1.2 ± 0.2 kg/m2 ; P < 0.05). MET+SITA gave a greater increase of first phase(2-10 min) insulin secretion and arginine-stimulated response (720.3 ± 299.0 to 995.5 ± 370.3 pmol/L and 3.2 ± 0.6 to 4.8 ± 1.0 pmoL/min, respectively, both P < 0.05) compared with MET and SITA. Similarly, MET+SITA was more effective in increasing OGTT-based glucose sensitivity (55.7 ± 11.3 to 108 ± 56.2 pmol x min-1 m-2 x mM-1 ; P = 0.04) and insulin-stimulated glucose disposal (M/I: 2.2 ± 0.5 to 4.6 ± 1.3 mg/kg/min÷µIU/min/ml; P = 0.04; Matsuda index [SI]: 3.1 ± 0.4 to 5.7 ± 1.1; P = 0.03) compared with either MET or SITA. Disposition index (ISSI-2) increased with MET+SITA and SITA (both P < 0.05), while no significant change was observed in MET. Among MET+SITA women, 33% reverted to normal glucose tolerance (NGT) compared with 14% with MET and 7% with SITA (P < 0.05). CONCLUSION: This study shows that MET+SITA is superior to SITA and MET monotherapy regarding beta-cell function and insulin sensitivity improvement in IGR women with previous GDM, and may offer a potential pharmacologic intervention to reduce the risk of type 2 diabetes in this high-risk population.

Update on proteomic studies of formalin-fixed paraffin-embedded tissues.

Introduction: This review is an update on recent progress in proteomic studies of formalin-fixed paraffin-embedded (FFPE) tissues, which open the opportunity to investigate diseases and research potential biomarkers, particularly when availability of fresh/frozen tissues is low. Areas covered: We described improvement of existing protocols or the new ones regarding deparaffinization and protein extraction of FFPE samples published from 2014 to today. Moreover, the growing interest to use FFPE tissues for mass spectrometry imaging approach is presented together with the search of post-translational modifications. Expert opinion: In the last few years, the number of papers using FFPE tissues in proteomic analysis is growing. The interest to apply proteomic analysis to FFPE tissues lies in the easy accessibility of a great number of samples from archives. Nevertheless, standardization in the approach among the different researchers is not achieved, making essentially incomparable the results obtained. This limit should be overcome.

Anti-Inflammatory Activities of Marine Algae in Neurodegenerative Diseases.

Neuroinflammation is one of the main contributors to the onset and progression of neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Microglial and astrocyte activation is a brain defense mechanism to counteract harmful pathogens and damaged tissues, while their prolonged activation induces neuroinflammation that can trigger or exacerbate neurodegeneration. Unfortunately, to date there are no pharmacological therapies able to slow down or stop the progression of neurodegeneration. For this reason, research is turning to the identification of natural compounds with protective action against these diseases. Considering the important role of neuroinflammation in the onset and development of neurodegenerative pathologies, natural compounds with anti-inflammatory activity could be good candidates for developing effective therapeutic strategies. Marine organisms represent a huge source of natural compounds, and among them, algae are appreciated sources of important bioactive components such as antioxidants, proteins, vitamins, minerals, soluble dietary fibers, polyunsaturated fatty acids, polysaccharides, sterols, carotenoids, tocopherols, terpenes, phycobilins, phycocolloids, and phycocyanins. Recently, numerous anti-inflammatory compounds have been isolated from marine algae with potential protective efficacy against neuroinflammation. This review highlights the key inflammatory processes involved in neurodegeneration and the potential of specific compounds from marine algae to counteract neuroinflammation in the CNS.

Italian Investigation on Mental Health Workers' Attitudes Regarding Personal Recovery From Mental Illness.

This study aimed to investigate attitudes toward personal recovery in a sample of 436 healthcare professionals and students of psychiatric rehabilitation techniques through the Italian version of the recovery knowledge inventory (RKI). The sample in our study showed a good global orientation toward recovery. Statistically significant differences were found among mental health professionals based on gender difference, professional role, and level of experience. Women seemed more inclined to accept users' decision-making processes, including therapeutic risk-taking. Nurses seemed more cautious in considering the users able to "live beyond their illness". Professionals with fewer than 15 years of experience had more favorable attitudes and expectations than the more experienced respondents. Students had more optimistic expectations regarding recovery than nurses and social workers. Academic curriculum development for students and training courses for mental health professionals could further improve the homogeneity in attitudes and skills in the support of users' "unique" recovery processes.

Influence of high density lipoprotein cholesterol levels on circulating monocytic angiogenic cells functions in individuals with type 2 diabetes mellitus.

BACKGROUND: High-density lipoproteins (HDLs) can exert anti-atherogenic effects. On top of removing excess cholesterol through reverse cholesterol transport, HDLs play beneficial actions on endothelial function and integrity. In particular, HDLs are strong determinant of endothelial progenitor cells (EPCs) number and function. To gain further insights into such an effect we characterized in vitro functionality of circulating "early" EPCs obtained from 60 type 2 diabetes individuals with low HDL-cholesterol (HDL-C) and 59 with high HDL-C levels. METHODS: After an overnight fast, venous blood was drawn in EDTA tubes and processed within 2-h from sampling. Peripheral blood mononuclear cells were isolated and plated on fibronectin coated culture dishes; after 3 days culture, adherent cells positive for Dil-ac-LDL/Lectin dual fluorescent staining were identified as monocytic angiogenic cells (MACs). After 5-7 days culture in EBM-2 medium, adherent cells were evaluated for viability/proliferation (MTT assay), senescence (beta-galactosidase activity detection), migration (modified Boyden chamber using VEGF as chemoattractant), adhesion capacity (on fibronectin-coated culture dishes) and ROS production (ROS-sensitive fluorescent probe CM-H2DCFDA). RESULTS: MACs obtained from diabetic individuals with high HDL-C had 23% higher viability compared to low HDL-C (111.6 ± 32.7% vs. 90.5 ± 28.6% optical density; p = 0.002). H2O2 exposure impaired MACs viability to a similar extent in both groups (109.2 ± 31.7% vs. 74.5 ± 40.8% in high HDL-C, p < 0.0001; 88.3 ± 25.5% vs. 72.3 ± 22.5% in low-HDL, p = 0.004). MACs senescence was comparable in the two groups (102.7 ± 29.8% vs. 99.2 ± 27.8%; p = 0.703) and was only slightly modified by exposure to H2O2. There was no difference in the MACs migration capacity between the two groups (91.3 ± 34.2% vs. 108.7 ± 39.5%; p = 0.111), as well as in MACs adhesion capacity (105.2 ± 32.7% vs. 94.1 ± 26.1%; p = 0.223). Finally, ROS production was slightly thought not significantly higher in MACs from type 2 diabetes individuals with low- than high-HDL. After stratification of HDL-C levels into quartiles, viability (p < 0.0001) and adhesion (p = 0.044) were higher in Q4 than in Q1-Q3. In logistic regression analysis, HDL-C was correlated to MACs viability and adhesion independently of HbA1c or BMI, respectively. CONCLUSIONS: Our data suggest that in type 2 diabetes subjects, HDL-cholesterol is an independent determinant of circulating MACs functional capacities-mainly viability, to a lesser extent adhesion-likely contributing also through this mechanism to cardiovascular protection even in type 2 diabetes.

A Proteomic Approach to Uncover Neuroprotective Mechanisms of Oleocanthal against Oxidative Stress.

Neurodegenerative diseases represent a heterogeneous group of disorders that share common features like abnormal protein aggregation, perturbed Ca2+ homeostasis, excitotoxicity, impairment of mitochondrial functions, apoptosis, inflammation, and oxidative stress. Despite recent advances in the research of biomarkers, early diagnosis, and pharmacotherapy, there are no treatments that can halt the progression of these age-associated neurodegenerative diseases. Numerous epidemiological studies indicate that long-term intake of a Mediterranean diet, characterized by a high consumption of extra virgin olive oil, correlates with better cognition in aged populations. Olive oil phenolic compounds have been demonstrated to have different biological activities like antioxidant, antithrombotic, and anti-inflammatory activities. Oleocanthal, a phenolic component of extra virgin olive oil, is getting more and more scientific attention due to its interesting biological activities. The aim of this research was to characterize the neuroprotective effects of oleocanthal against H2O2-induced oxidative stress in neuron-like SH-SY5Y cells. Moreover, protein expression profiling, combined with pathways analyses, was used to investigate the molecular events related to the protective effects. Oleocanthal was demonstrated to counteract oxidative stress, increasing cell viability, reducing reactive oxygen species (ROS) production, and increasing reduced glutathione (GSH) intracellular level. Proteomic analysis revealed that oleocanthal significantly modulates 19 proteins in the presence of H2O2. In particular, oleocanthal up-regulated proteins related to the proteasome, the chaperone heat shock protein 90, the glycolytic enzyme pyruvate kinase, and the antioxidant enzyme peroxiredoxin 1. Moreover, oleocanthal protection seems to be mediated by Akt activation. These data offer new insights into the molecular mechanisms behind oleocanthal protection against oxidative stress.

Toward the Standardization of Mitochondrial Proteomics: The Italian Mitochondrial Human Proteome Project Initiative.

The Mitochondrial Human Proteome Project aims at understanding the function of the mitochondrial proteome and its crosstalk with the proteome of other organelles. Being able to choose a suitable and validated enrichment protocol of functional mitochondria, based on the specific needs of the downstream proteomics analysis, would greatly help the researchers in the field. Mitochondrial fractions from ten model cell lines were prepared using three enrichment protocols and analyzed on seven different LC-MS/MS platforms. All data were processed using neXtProt as reference database. The data are available for the Human Proteome Project purposes through the ProteomeXchange Consortium with the identifier PXD007053. The processed data sets were analyzed using a suite of R routines to perform a statistical analysis and to retrieve subcellular and submitochondrial localizations. Although the overall number of identified total and mitochondrial proteins was not significantly dependent on the enrichment protocol, specific line to line differences were observed. Moreover, the protein lists were mapped to a network representing the functional mitochondrial proteome, encompassing mitochondrial proteins and their first interactors. More than 80% of the identified proteins resulted in nodes of this network but with a different ability in coisolating mitochondria-associated structures for each enrichment protocol/cell line pair.

Evidence for two distinct phenotypes of chronic kidney disease in individuals with type 1 diabetes mellitus.

AIMS/HYPOTHESIS: In a retrospective, observational, cross-sectional, single-centre study, we assessed the prevalence and correlates of different CKD phenotypes (with and without albuminuria) in a large cohort of patients of white ethnicity with type 1 diabetes. METHODS: From 2001 to 2009, 408 men and 369 women with type 1 diabetes (age 40.2 ± 11.7 years, diabetes duration 19.4 ± 12.2 years, HbA1c 7.83 ± 1.17% [62.0 ± 12.9 mmol/mol]) were recruited consecutively. Albumin-to-creatinine ratio (ACR) and eGFR (Modification of Diet in Renal Disease) were obtained for all individuals, together with CKD stage. Diabetic retinopathy and peripheral polyneuropathy were detected in 41.5% and 8.1%, respectively, and cardiovascular disease (CVD) occurred in 8.5%. Adjudications of CKD phenotype were made by blinded investigators. RESULTS: Normo- (ACR <3.4), micro- (ACR 3.4-34) or macroalbuminuria (ACR ≥34 mg/mmol) were present in 91.6%, 6.4% and 1.9% of individuals, respectively. eGFR categories 1 (≥90 ml min-1 [1.73 m]-2), 2 (60-89 ml min-1 [1.73 m]-2) and 3 (<60 ml min-1 [1.73 m]-2) were present in 57.3%, 39.0% and 3.7%, respectively. The majority of participants had no CKD (89.4%), while stages 1-2 and ≥3 CKD were detected in 6.8% and 3.7%, respectively. The albuminuric (Alb+) and non-albuminuric (Alb-) phenotypes were present in 12 (41.4%) and 17 (58.6%) individuals with stage ≥3 CKD, respectively. Individuals with an ACR <3.4 mg/mmol were subdivided into those with normal albuminuria (<1.1 mg/mmol; 77.2%) and mildly increased albuminuria (1.1-3.4 mg/mmol; 14.4%), and individuals with stage 2 CKD were subdivided into those with eGFR 75-89 ml min-1 [1.73 m]-2 and 60-74 ml min-1 [1.73 m]-2. ACR <3.4 mg/mmol (88.7%) and even <1.1 mg/mmol (70.4%) were common in individuals with eGFR 60-74 ml min-1 [1.73 m]-2. The prevalence of ACR <1.1 mg/mmol was lower but still significant (34.5%) in those with stage ≥3 CKD. In logistic regression analysis, stages 1-2 and ≥3 CKD were independently associated with age, HbA1c, γ-glutamyltransferase, fibrinogen, hypertension, but not with sex, BMI, smoking, HDL-cholesterol or triacylglycerol. Inclusion of advanced retinopathy removed HbA1c from the model. The CKD Alb+ phenotype correlated with diabetes duration, HbA1c, HDL-cholesterol, fibrinogen and hypertension, while the CKD Alb- phenotype was associated with age and hypertension, but not with diabetes duration, HbA1c and fibrinogen. CONCLUSIONS/INTERPRETATION: The Alb- CKD phenotype is present in a significant proportion of individuals with type 1 diabetes supporting the hypothesis of two distinct pathways (Alb+ and Alb-) of progression towards advanced kidney disease in type 1 diabetes. These are probably distinct pathways as suggested by different sets of covariates associated with the two CKD phenotypes.

The rs12917707 polymorphism at the UMOD locus and glomerular filtration rate in individuals with type 2 diabetes: evidence of heterogeneity across two different European populations.

BACKGROUND: UMOD variability has been associated at a genome-wide level of statistical significance with glomerular filtration rate (GFR) in Swedish individuals with type 2 diabetes (T2D; n = 4888). Whether this finding is extensible also to diabetic patients from other populations deserves further study. Our aim was to investigate the relationship between UMOD variability and GFR in patients with T2D from Italy. METHODS: Genotyping of the single nucleotide polymorphism (SNP) rs12917707 at the UMOD locus has been carried out in 3087 individuals from four independent Italian cohorts of patients with T2D by TaqMan allele discrimination. RESULTS: In none of the four study cohorts was rs12917707 significantly associated with GFR (P > 0.05 for all). Similar results were obtained when the four samples were pooled and analyzed together (ß = 0.83, P = 0.19). Such effect was strikingly smaller than that previously reported in Swedish patients (P for heterogeneity = 1.21 × 10-7). CONCLUSIONS: The previously reported strong association between rs12917707 and GFR in diabetic patients from Sweden is not observed in Italian diabetic patients, thus clearly pointing to a heterogeneous effect across the two different samples. This suggests that UMOD is a strong genetic determinant of kidney function in patients with T2D in some, but not all, populations.

Salivary psoriasin (S100A7) correlates with diffusion capacity of carbon monoxide in a large cohort of systemic sclerosis patients.

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by progressive fibrosis of the skin and the internal organs. In a previous work we suggested a correlation between levels of salivary psoriasin (S100A7) and pulmonary involvement in SSc patients. The goals of this study are to determine the distribution characteristics of psoriasin in whole saliva (WS) of SSc and healthy donor populations and define its predictive value on diffusion capacity of carbon monoxide (DLCO), along with others clinical parameters. METHODS: Salivary level of psoriasin was determined by ELISA kit in 134 SSc patients, 63 Raynaud syndrome patients, 40 patients affected by other connective diseases (non-case) and 74 healthy control subjects. RESULTS: A significant increase of salivary psoriasin was observed in SSc patients when compared with other healthy and pathological controls. Moreover, we confirmed the efficacy of salivary psoriasin to correlate with DLCO in a large cohort of SSc patients. CONCLUSIONS: Overall our results suggest a rapid, non invasive and low costing method which can help clinicians in the evaluation of SSc pulmonary involvement.

Proteomics insight into psychiatric disorders: an update on biological fluid biomarkers.

INTRODUCTION: Psychiatric disorders are severe, debilitating and heterogeneous diseases with a high impact on public health. In this review we address state of the art clinical approaches to diagnose psychiatric disorders and underline the necessity to found new tools to help clinicians. Areas covered: We provide an update on proteomic studies and suggest potential biomarkers focusing on schizophrenia (SCZ), bipolar disorder (BD), and major depression (MD). In particular, we direct our attention to proteomic results obtained from studies on biological fluids. We also show an interaction analysis of differentially expressed proteins found in SCZ, BD and MD. Expert commentary: To date, there is a need to find molecular biomarkers for psychiatric disorders. The use of a proteomic approach allows protein fingerprints to be defined in normal and pathological states. We believe that saliva is an intriguing biological fluid, whose proteomic study in psychiatric disorders is still in its early stages.

Is personal recovery in schizophrenia predicted by low cognitive insight?

Recovery is a widely discussed concept in the field of research, treatment, and public policy regarding serious mental illness, and mainly schizophrenia. Aim of our study was to assess the relationship between personal recovery and prediction variables, as psychopathology, neurocognition, clinical and cognitive insight, and social functioning in inpatients affected by schizophrenia, with a special interest on cognitive insight. We assessed 76 inpatients affected by schizophrenia at their hospital discharge. Instruments included the Beck Cognitive Insight Scale, the Insight Scale and the Recovery Assessment Scale to assess the cognitive and clinical insight, and personal recovery. The neurocognitive assessment was represented by a single factor score produced by a principal components analysis of a neurocognitive test battery. Social functioning was measured also. Low self-reflectiveness of cognitive insight represented the best predictors of personal recovery. The relationship between cognitive insight and recovery found in this study may contribute to develop tailored interventions, taking into account the personal sense of recovery, despite the psychopathological evaluation.

First evidence of TRPV5 and TRPV6 channels in human parathyroid glands: possible involvement in neoplastic transformation.

The parathyroid glands play an overall regulatory role in the systemic calcium (Ca(2+)) homeostasis. The purpose of the present study was to demonstrate the presence of the Ca(2+) channels transient receptor potential vanilloid (TRPV) 5 and TRPV6 in human parathyroid glands. Semi-quantitative and quantitative PCR was carried out to evaluate the presence of TRPV5 and TRPV6 mRNAs in sporadic parathyroid adenomas and normal parathyroid glands. Western blot and immunocytochemical assays were used to assess protein expression, cellular localization and time expression in primary cultures from human parathyroid adenoma. TRPV5 and TRPV6 transcripts were then identified both in normal and pathological tissues. Predominant immunoreactive bands were detected at 75-80 kD for both vanilloid channels. These channels co-localized with the calcium-sensing receptor (CASR) on the membrane surface, but immunoreactivity was also detected in the cytosol and around the nuclei. Our data showed that western blotting recorded an increase of protein expression of both channels in adenoma samples compared with normal glands suggesting a potential relation with the cell calcium signalling pathway and the pathological processes of these glands.