Bisogna portare il pensiero della morte come i signori della epoca portavano il falcone sulla spalla.

Il titolo è tratto da un pensiero, forse un poco conturbante, ma certamente necessario, di Michel Eyquem de Montaigne e serve per fare un bilancio onesto. Infatti la scelta di essere agnostici qualifica coloro che scrivono come scettici e relativisti moderati, riducendo molti loro pensieri al solo strumentalismo operazionale, proposto da Percy Williams Bridgman. A riguardo, importante è la critica delle metodologie e procedure, comunemente impiegate, e come cautelarsi dagli errori grossolani, sempre possibili. Infatti una analisi approfondita della logica della ricerca scientifica, ma non solo, constata la mancanza di verità sicure ed assolute, ritrovando invece solo alcune certezze, spesso molto precarie e provvisorie. In questo contesto, la conoscenza scientifica si struttura costruendo una sua teoria, in accordo con il matematico e filosofo Federigo Enriques, e riconoscendo come la scienza dipenda dall’ambiente, secondo la lezione del matematico e fisico Erwin Schrödinger. Dopodiché ritornando al pensiero espresso dal titolo, in una postfazione a mo’ di commiato, le Tuscolane di Cicerone offrono l’occasione per una serena disamina dei limiti della esistenza umana

Horses with equine recurrent uveitis have an activated CD4+ T-cell phenotype that can be modulated by mesenchymal stem cells in vitro.

Equine recurrent uveitis (ERU) is an immune-mediated disease causing repeated or persistent inflammatory episodes which can lead to blindness. Currently, there is no cure for horses with this disease. Mesenchymal stem cells (MSCs) are effective at reducing immune cell activation in vitro in many species, making them a potential therapeutic option for ERU. The objectives of this study were to define the lymphocyte phenotype of horses with ERU and to determine how MSCs alter T-cell phenotype in vitro. Whole blood was taken from 7 horses with ERU and 10 healthy horses and peripheral blood mononuclear cells were isolated. The markers CD21, CD3, CD4, and CD8 were used to identify lymphocyte subsets while CD25, CD62L, Foxp3, IFNγ, and IL10 were used to identify T-cell phenotype. Adipose-derived MSCs were expanded, irradiated (to control proliferation), and incubated with CD4+ T-cells from healthy horses, after which lymphocytes were collected and analyzed via flow cytometry. The percentages of T-cells and B-cells in horses with ERU were similar to normal horses. However, CD4+ T-cells from horses with ERU expressed higher amounts of IFNγ indicating a pro-inflammatory Th1 phenotype. When co-incubated with MSCs, activated CD4+ T-cells reduced expression of CD25, CD62L, Foxp3, and IFNγ. MSCs had a lesser ability to decrease activation when cell-cell contact or prostaglandin signaling was blocked. MSCs continue to show promise as a treatment for ERU as they decreased the CD4+ T-cell activation phenotype through a combination of cell-cell contact and prostaglandin signaling

Effect of Arginine Infusion on Ghrelin Secretion in Growth Hormone-Sufficient and GH-Deficient Children.

Background: The physiological link between ghrelin and growth hormone (GH) has not yet been fully clarified. Furthermore, the existence of a negative feedback mechanism between growth hormone\u2013insulin-like growth factor (GH\u2013IGF)-I axis and ghrelin and the influence of amino acids on ghrelin secretion in children remain matters of debate. Objectives: To understand the regulation of ghrelin secretion and clarify the relationship between ghrelin and GH secretion in GH-deficient (GHD) and GH-sufficient (GHS) children Patients and Methods: Ten GHD (male/female [M/F], 6/4; age [mean \ub1 SEM], 10.7 \ub1 0.9 years) and 10 GHS prepubertal children (M/F, 6/4; age [mean \ub1 SEM], 10.3 \ub1 0.6 years), underwent an arginine (ARG) test (infusion, 0.5 g/kg, iv). Levels of GH, total ghrelin, and acylated ghrelin (AG) were assayed every 30 min from 0 to +120 min. Results: Peak GH values were lower in GHD subjects than in GHS subjects (P < 0.0001). The baseline levels, peak levels, or area under the curves (AUC) for total ghrelin and AG were similar between GHD and GHS children. ARG infusion was followed by a slight to significant decrease in total ghrelin levels, but not AG levels, both in GHD and GHS subjects with a nadir at +30 min. No correlation was seen between GH, total ghrelin, or AG response and ARG infusion. Conclusions: Total ghrelin and AG levels seemed unaffected by GH status in prepubertal children. ARG infusion was unable to blunt ghrelin secretion irrespective of GH status in childhood. Moreover, since ARG influences GH secretion via modulation of somatostatin release, ghrelin secretion seems to be partially refractory to somatostatin action

Effects of Growth Hormone (GH) Therapy Withdrawal on Glucose Metabolism in Not Confirmed GH Deficient Adolescents at Final Height.

CONTEXT OBJECTIVE: Growth hormone deficiency (GHD) is associated with insulin resistance and diabetes, in particular after treatment in children and adults with pre-existing metabolic risk factors. Our aims were. i) to evaluate the effect on glucose metabolism of rhGH treatment and withdrawal in not confirmed GHD adolescents at the achievement of adult height; ii) to investigate the impact of GH receptor gene genomic deletion of exon 3 (d3GHR). DESIGN SETTING: We performed a longitudinal study (1 year) in a tertiary care center. METHODS: 23 GHD adolescent were followed in the last year of rhGH treatment (T0), 6 (T6) and 12 (T12) months after rhGH withdrawal with fasting and post-OGTT evaluations. 40 healthy adolescents were used as controls. HOMA-IR, HOMA%\u3b2, insulinogenic (INS) and disposition (DI) indexes were calculated. GHR genotypes were determined by multiplex PCR. RESULTS: In the group as a whole, fasting insulin (p<0.05), HOMA-IR (p<0.05), insulin and glucose levels during OGTT (p<0.01) progressively decreased from T0 to T12 becoming similar to controls. During rhGH, a compensatory insulin secretion with a stable DI was recorded, and, then, HOMA\u3b2 and INS decreased at T6 and T12 (p<0.05). By evaluating the GHR genotype, nDel GHD showed a decrease from T0 to T12 in HOMA-IR, HOMA\u3b2, INS (p<0.05) and DI. Del GHD showed a gradual increase in DI (p<0.05) and INS with a stable HOMA-IR and higher HDL-cholesterol (p<0.01). CONCLUSIONS: In not confirmed GHD adolescents the fasting deterioration in glucose homeostasis during rhGH is efficaciously coupled with a compensatory insulin secretion and activity at OGTT. The presence of at least one d3GHR allele is associated with lower glucose levels and higher HOMA-\u3b2 and DI after rhGH withdrawal. Screening for the d3GHR in the pediatric age may help physicians to follow and phenotype GHD patients also by a metabolic point of view

SAT0460 INGESTION OF LEMON JUICE MAY MODULATE BONE METABOLISM.

Background:An association between bone health and consumption of citrus fruits have been previously reported; however, the effect of lemon juice on bone metabolism have not been explored yet.Objectives:To investigate bone metabolic changes in postmenopausal women assuming lemon juice.Methods:Participants were postmenopausal osteoporotic women without history of clinical fractures who agreed to enrich their diet with lemon juice (Acti Lemon, Polenghi) over a 2-month period. The daily juice dose of 30 ml we suggested was equivalent to one Sicilian organic lemon. Surrogate markers of bone formation as procollagen type 1 N-propeptide (P1NP) and of bone resorption as C-terminal telopeptide of type I collagen (CTX), but also some regulators of bone metabolism as RANK-L, OPG, RANK-L/OPG ratio and sclerostin were assessed at baseline and then at 1 and 2 months after lemon juice administration. Controls were represented by a placebo group of age-matched osteoporotic postmenopausal women.Results:47 participants [mean age 60.2 ± 4.1 yr.] completed the study, without reporting any adverse events. Lemon juice was well tolerated. Over the observation period modifications of bone metabolism occurred: we detected a decreased RANK-L/OPG ratio and increased CTX levels at all time points vs. baseline. Particularly, change at month-1 of sclerostin (versus baseline) has been positively associated with change at month-1 and month-2 of CTX (r=0.46, p=0.01 and r=0.43, p=0.01, respectively). Change at month-1 of OPG was positively associated with change at month-1 of P1NP (r=0.49, p=0.006). Change at month-1 of RANKL/OPG has been related with variation at day 30 of P1NP (r=-0.44, p=0.013). Variation of P1NP at month-1 was related with sclerostin variation at day 30 (r=-0.56, p=0.02) and month-2 vs. baseline value (r=0.44, p=0.017) and with sclerostin variation between month-1 and month-2 (r=0.69, p<0.001). Variation of P1NP between month-1 and month-2 was associated with RANKL change at month-1 (r=-0.35, p=0.05), with sclerostin change at month-1 (r=-0.49, p=0.008) and with sclerostin change between month-1 and month-2 (r=0.41, p=0.028). At a multiple regression analysis the change of P1NP between month-1 and month-2 was independently predicted by the change of sclerostin at month-1 (ß=-1.5, SE 0.5, p=0.006), after correcting for age, BMI and change of RANKL and CTX levels at month-1. No significant modifications raised from controls.Conclusion:Drinking lemon juice may boost bone metabolic changes involving both bone resorption and bone formation.Disclosure of Interests:None declare

A Novel Muco-Gingival Approach for Immediate Implant Placement to Obtain Soft- and Hard-Tissue Augmentation

The aim of this article is to describe a novel approach combining muco-gingival, regenerative and prosthetics concepts for immediate implant insertion that overcomes the limits traditionally considered as contraindications for Type 1 flapless implant positioning, simultaneously obtaining soft- and hard-tissue augmentation. After pre-surgical CBCT evaluation, the surgical technique consisted in the execution of a lateral-approach coronally advanced envelope flap, with oblique submarginal interproximal incisions directed towards the flap’s center of rotation (the tooth to be extracted); after buccal-flap elevation, the atraumatic extraction of the tooth was performed. Following guided implant insertion, a mixture of biomaterial and autologous bone was placed, stabilized by a pericardium membrane and a connective-tissue graft sutured in the inner aspect of the buccal flap. The peri-implant soft tissues were conditioned with a provisional crown until the shape and position for the mucosal scallop to resemble the gingival margin of the adjacent corresponding tooth were obtained; then, the definitive screw-retained restoration was placed. Within the limitations of this case report, the proposed immediate implant placement approach combining CTG application and buccal bone regeneration showed the possibility of obtaining 1-year-follow-up implant success, stable bone level, good esthetic results and high patient satisfaction

Alexithymia and psychological distress affect perceived quality of life in patients with type 2 diabetes mellitus

Backgrounds: Psychological factors may affect patients' ability to cope with chronic illness, which occur with a high incidence as they represent age related disorder. Anxiety, depression and alexithymia could specifically interfere with compliance and adherence leading to predictable consequences and predicting morbidity and mortality independently of several confounders. The present work aims at investigating the relationship between alexithymia and affective dimension such as anxiety and depression levels, and health related quality of life in T2DM patients. Particularly, alexithymia was analyzed in its three main facets and time since diagnosis was considered with also metabolic control. Methods: Forty seven patients with T2DM were consecutively enrolled and assessed with a gold standard interview and with a psycho-diagnostic evaluation. Clinical psychological exploration consisted of HAM-A, BECK-II, SF-36 and TAS-20 administration. Statistical analysis was performed using IBM SPSS statistical version 25. Data were analyzed anonymously. Results: 47 participants showed moderate depressive symptoms as confirmed by the mean BDI-II and HAMA-A score (15.14 ± 8.95 and 24.31 ± 6.95, respectively), suggesting a high prevalence of anxiety in the enrolled subjects. It was observed a lower perceived QoL as resulted by the MCS and PCS mean values (37.68 ± 9.41 and 39.31 ± 12.29, respectively) and TAS-20 highlighted considerable mean values of 60.53 ± 7.93 in the recruited participants with a prevalence in EOT values (27.51± 4.27), in comparison with mean DID and DDF values (17.26 ± 5.52 and 15.48 ± 3.84, respectively). Conclusions: Our study may suggest a predictive role of alexithymia in patients with T2DM. Moreover, lower PCS and MCS, revealing worst perceived QoL were associated to both higher anxiety and disease duration

High-end normal adrenocorticotropic hormone and cortisol levels are associated with specific cardiovascular risk factors in pediatric obesity: a cross-sectional study.

BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) axis, and in particular cortisol, has been reported to be involved in obesity-associated metabolic disturbances in adults and in selected populations of adolescents. The aim of this study was to investigate the association between morning adrenocorticotropic hormone (ACTH) and cortisol levels and cardiovascular risk factors in overweight or obese Caucasian children and adolescents. METHODS: This cross-sectional study of 450 obese children and adolescents (aged 4 to 18 years) was performed in a tertiary referral center. ACTH, cortisol, cardiovascular risk factors (fasting and post-challenge glucose, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, and hypertension) and insulin resistance were evaluated. All analyses were corrected for confounding factors (sex, age, puberty, body mass index), and odds ratios were determined. RESULTS: ACTH and cortisol levels were positively associated with systolic and diastolic blood pressure, triglycerides, fasting glucose and insulin resistance. Cortisol, but not ACTH, was also positively associated with LDL-cholesterol. When adjusted for confounding factors, an association between ACTH and 2 h post-oral glucose tolerance test glucose was revealed. After stratification according to cardiovascular risk factors and adjustment for possible confounding factors, ACTH levels were significantly higher in subjects with triglycerides 6590th percentile (P 5.92 pmol/l) and cortisol (>383.5 nmol/l) although within the normal range were associated with increases in cardiovascular risk factors in this population. CONCLUSIONS: In obese children and adolescents, high morning ACTH and cortisol levels are associated with cardiovascular risk factors. High ACTH levels are associated with high triglyceride levels and hyperglycemia, while high cortisol is associated with hypertension and high LDL-cholesterol. These specific relationships suggest complex mechanisms through which the HPA axis may contribute to metabolic impairments in obesity, and merit further investigations