N-Polybenzylated alicyclic 1,2-diamines: cytotoxicity and G1 phase arrest in cancer cell line.

Cytotoxicity in the µM range was observed in cancer cell lines treated with N,N,N',N'-tetrabenzyl-4,5-diamino-2-cyclopentenone. Cell cycle analysis on HeLa cells showed a clear G1 phase arrest. A preliminary SAR on structural analogs was performed in order to identify the pharmacophores.

Neurobiological Correlates Shared Between Obesity, BED and Food Addiction.

The ubiquity of the obesity condition in the United States, Europe and other regions with developed economies will associate to a significant adverse impact on public health. Numerous data indicate that social, behavioral, neuroendocrine, and metabolic factors may encourage compulsive eating behaviors thus increasing the risk of obesity. Several pathological conditions overlap with excess weight. Among the most common, there are binge eating disorder (BED) and food addiction (FA), which share several neurobiological and behavioral aspects with substance addictions. BED has many features in common with addictive behavior, such as loss of control and the need to frequently repeat the dysfunctional pattern despite negative consequences. The food addiction hypothesis assumes that exposure to highly palatable foods alters the reward circuits of the brain, resulting in a behavioral phenotype similar to substance addiction and facilitating dysfunctional eating behaviors, such as binge eating crises. In this review, over 100 publications, researched on MEDLINE from 2000 until march 2021, were included since they evaluate neuroendocrine changes, emotional homeostatic factors and the reward circuit, associating them with exposure to highly palatable foods, loss of control, the way we eat, the increase in impulsiveness and the inability to change eating behavior despite the negative consequences related to overweight and obesity. Finally, understanding the underlying neurobiological circuits of compulsive eating behaviors and food addiction could result in a great therapeutic potential for patients suffering from ailments nutrition and obesity.

Menstrual Disorders Related to Eating Disorders.

Eating Disorders (ED) are associated with multiple physical complications that strongly affect the physical health of these young and fragile patients and can also cause significant mortality, the highest among psychiatric pathologies. Among the various organic complications, albeit still little known, the gynecological implications, up to infertility, are very widespread. Both among adolescent and adult patients, gynecological symptoms can be very widespread and range from menstrual irregularities to amenorrhea, from vaginitis to ovarian polycystosis, up to complications during the gestational phase and in postpartum, in addition to the possible consequences on the unborn child. Among the most frequent and significant gynecological disorders in women with ED, there are menstrual irregularities that may occur with oligomenorrhea or even amenorrhea. This symptom, although no longer part of the DSM-5 diagnostic criteria for defining Anorexia Nervosa (AN), must be considered a very relevant event in the overall evaluation of young women and adolescents with eating disorders. Functional Hypothalamic Amenorrhea in ED patients is related to psychological distress, excessive exercise, disordered eating, or a combination of these factors which results in suppression of the hypothalamic- pituitary-ovarian axis, resulting in hypoestrogenism. The objective of this paper is to summarize the causes and the mechanism underlying the menstrual disorders and to provide a better understanding of the correlation between the reproductive system and the mechanisms that regulate food intake and eating habits. In addition, early recognition of risk factors for eating disorders for gynecological implications can help put more accurate assessments of patients to prevent potentially fatal complications. The importance of the involvement of specialist gynecologists in the multidisciplinary team that has to follow patients with eating disorders is also discussed.

Design and methodologies of the POSTconditioning during coronary angioplasty in acute myocardial infarction (POST-AMI) trial.

BACKGROUND: Reperfusion remains the definitive treatment for acute myocardial infarction (AMI), but restoring blood flow carries the potential to exacerbate the ischemia-related injury. Postconditioning might modify reperfusion-induced adverse events. STUDY DESIGN: The POSTconditioning during Coronary Angioplasty in Acute Myocardial Infarction (POST-AMI) trial is a single-center, prospective, randomized study, with a planned inclusion of 78 patients with ST-elevation AMI. Patients will be randomly assigned to the postconditioning arm [primary angioplasty (PA) and stenting followed by brief episodes of ischemia-reperfusion early after recanalization] or non-postconditioning arm. All patients will be treated medically according to current international guidelines, including glycoprotein IIb/IIIa inhibitors before PA. The primary end point is to evaluate whether postconditioning, compared to plain PA, reduces infarct size estimated by cardiac magnetic resonance (CMR) at 30 +/- 10 days after the AMI. Secondary end points are microvascular obstruction observed at CMR, ST-segment resolution, angiographic myocardial blush grade <2, non-sustained/sustained ventricular tachycardia in the 48 h following PA, left ventricular remodeling and function at follow-up CMR, and the reduction of major adverse cardiac events at 30 days and 6 months. CONCLUSION: The POST-AMI trial will evaluate the usefulness of postconditioning in limiting infarct size during the early and late phases after AMI.

[Quality of the documents requesting and reporting CT scans: a retrospective study in four Italian hospitals]. / Qualità documentale di richieste e referti di TC: studio retrospettivo in quattro ospedali italiani.

A retrospective study was performed to evaluate the quality of CT scan request and report forms in four Italian hospitals in three different Regions. A sample of 800 request forms and corresponding reports in four hospitals were evaluated. Half of the analysed reports involved inpatients while the other half involved outpatients. The four participating hospitals were all of different typology. Study results show that the request forms do not always contain important information such as the suspected diagnosis or name of the requesting physician. Quality indicators of the examined documents were evaluated in relation to their impact on clinical safety.

Gender Dysphoria, Eating Disorders and Body Image: An Overview.

BACKGROUND: Gender dysphoria is a clinical condition in which a state of inner suffering, stress and anxiety is detected when biological sex and a person's gender identity do not coincide. People who identify themselves as transgender people are more vulnerable and may have higher rates of dissatisfaction with their bodies which are often associated with a disorderly diet in an attempt to change the bodily characteristics of the genus of birth and, conversely, to accentuate the characteristics of the desired sexual identity. AIM: The purpose of this work is to examine the association between dissatisfaction with one's own body and eating and weight disorders in people with gender dysphoria. RESULTS: Gender dysphoria and eating disorders are characterized by a serious discomfort to the body and the body suffers in both conditions. The results of our study suggest that rates of pathological eating behaviors and symptoms related to a disordered diet are high in patients with gender dysphoria and that standard screening for these symptoms must be considered in both populations at the time of evaluation and during the course of the treatment. CONCLUSION: In light of this evidence, clinicians should always investigate issues related to sexuality and gender identity in patients with eating disorders, to develop more effective prevention measures and better strategies for therapeutic intervention.

Recent Advances in Treatment of Childhood Obesity.

Childhood obesity has assumed epidemic proportions and is currently one of the most widespread public health problems. Many are the factors involved in the pathogenesis of excess weight with interactions between genetic, environmental and biological factors and therefore, also the therapeutic approach must be multidisciplinary and multidimensional. In this review of the literature, we report the contiguity of childhood obesity with eating disorders and the importance of involving the family context in order to induce stable lifestyle changes, both in relation to dietary and nutritional habits, but also in increasing physical activity. Finally, among the therapeutic options, although for selected cases, pharmacotherapy and bariatric surgery can be used as treatment strategies.

Obesity: The New Global Epidemic Pharmacological Treatment, Opportunities and Limits for Personalized Therapy.

BACKGROUND: The increase in global obesity rates over the past three decades has been remarkable, a true epidemic, both in developed and in developing countries. The projections, based on current trends, suggest an increase in the prevalence of obesity at 60% in adult men, 40% in adult women and 25% in children in 2050. Given the limitations of lifestyle and surgery interventions bariatric, drug therapy approaches for the treatment of obesity, therefore become important options. AIM: The purpose of this review is a review of the literature, based on research on MEDLINE until 2019, on the possible pharmacological options in the treatment of obesity. RESULTS: Currently, the FDA has approved several molecules for the treatment of obesity, both in monotherapy and in combination. Pharmacological monotherapies focus mainly on a single protein target and include orlistat, lorcaserin and liraglutide while the combination molecules propose a multitarget approach and include phentermine/topiramate and naltrexone/bupropion. All the approved drugs showed, in the different studies, a weight reduction of at least 5%, compared to placebo, in 52 weeks of observation. Phentermine-topiramate and liraglutide have been associated with the highest probability of at least 5% weight loss. Liraglutide and naltrexone-bupropion had the lowest rates of therapy discontinuation due to adverse events. CONCLUSION: The drugs, associated with the standard diet and/or exercise protocols, represent a good therapeutic opportunity to allow not only weight loss but also to reduce the risk of developing diseases caused by obesity, particularly cardiovascular diseases, and to maintain the set objectives over time. However, future research on the pharmacological treatment of obesity should encourage greater personalization of therapy, given the differences in safety, efficacy and response to therapy, in the different subpopulations of patients with obesity.

Depression and Obesity: Analysis of Common Biomarkers.

Depression and obesity are very common pathologies. Both cause significant problems of both morbidity and mortality and have decisive impacts not only on the health and well-being of patients, but also on socioeconomic and health expenditure aspects. Many epidemiological studies, clinical studies and meta-analyses support the association between mood disorders and obesity in relationships to different conditions such as the severity of depression, the severity of obesity, gender, socioeconomic status, genetic susceptibility, environmental influences and adverse experiences of childhood. Currently, both depression and obesity are considered pathologies with a high-inflammatory impact; it is believed that several overlapping factors, such as the activation of the cortico-adrenal axis, the exaggerated and prolonged response of the innate immune system and proinflammatory cytokines to stress factors and pathogens-as well as alterations of the intestinal microbiota which promote intestinal permeability-can favor the expression of an increasingly proinflammatory phenotype that can be considered a key and common phenomenon between these two widespread pathologies. The purpose of this literature review is to evaluate the common and interacting mechanisms between depression and obesity.

Supramolecular assemblies based on amphiphilic Mn2+-complexes as high relaxivity MRI probes.

In the research field of MRI contrast agents (CAs), amphiphilic paramagnetic complexes are typically sought for the increased plasmatic half-life and high relaxivity values, but limited examples of amphiphilic Mn2+-based CAs have been reported to date. In this work the Mn2+-complexes of six original amphiphilic ligands (three EDTA-like ligands and three 1,4-DO2A derivatives) embodying one or two aliphatic chains were evaluated as potential MRI contrast agents and compared. Strong self-association into micelles resulted in a relaxivity (r1) enhancement (ca. 80% with respect to MnEDTA) as a consequence of the increased molecular tumbling rate of the supramolecular aggregate. In the case of bis-substituted systems the r1 gain is much higher due to the restricted local rotation of the chelates about the pendant aliphatic chains (r1 in the range 12.6-18.4 mM-1 s-1, 2-3 times higher than for the micelles obtained with single-chain EDTA systems). Furthermore, these amphiphilic chelates tightly bind to human serum albumin (HSA) with association constants KA in the range 104-105 M-1. The resulting supramolecular adducts achieve remarkable relaxivity values, in the range 50-60 mM-1 s-1 for the MnEDTA-like chelates and 27-30 mM-1 s-1 for the 1,4-DO2A-like systems (at 298 K and 20 MHz), thanks to their fast water exchange rate.

Case report: role of bedside ultrasonography in early diagnosis of myonecrosis rapidly developed in deep soft tissue infections.

BACKGROUND: Myonecrosis can rapidly develop in soft tissue necrotizing infections, often with initial sparing of the skin. Despite the improvements in management of necrotizing soft tissue infections, mortality remains high, according to the location, microbial agents and comorbidities, ranging between 17 and 46 %. A prompt diagnosis represents the greatest challenge for the emergency physician. CASE REPORT: We describe the case of a patient with a history of hypertension and arrhythmia who developed nonclostridial necrotizing fasciitis with extensive myonecrosis, after articular infiltration procedure. A bedside focused ultrasonography (US) revealed disappearance of the regular fibrillar architecture of the long head of biceps muscle, with diffuse abnormal hyperechogenicity assembled in a "clod pattern". Computed tomography (CT) of the right arm did not depict muscle involvement, but showed a small gas collection around the shoulder, spreading to the subclavian region behind the major pectoral muscle. Necrotizing fasciitis with wide myonecrosis was confirmed by surgical debridement. Microbiological results showed a Staphylococcus aureus infection, managed by a selected antibiotic therapy. The patient was discharged after a small period of mechanical ventilation. CONCLUSION: This is the first report of a previously healthy patient developing a nonclostridial necrotizing fasciitis with extensive myonecrosis attributable to infiltrative procedure and detected early by bedside US in emergency department. The role of bedside US in the emergency setting may save time for the prompt management of life-threatening necrotizing infections.

Postconditioning during coronary angioplasty in acute myocardial infarction: the POST-AMI trial.

BACKGROUND: Postconditioning (PC) has been suggested to reduce myocardial damage during primary percutaneous coronary intervention (PPCI), nevertheless clinical experience is limited. We aimed to explore the cardioprotective effect of PC using cardiac magnetic resonance (CMR) in ST-elevation myocardial infarction (STEMI) patients treated by PPCI. METHODS: A total of 78 patients with first STEMI (aged 59±12 years) referred for PPCI, were stratified for STEMI location and randomly assigned to conventional PPCI or PPCI with PC. All patients, with occluded infarct related artery and no collateral circulation, received abciximab intravenously before PPCI. After reperfusion by effective direct stenting, control subjects underwent no further intervention, while in treated patients PC was performed within 1 min of reflow by 4 cycles of 1-minute inflation and 1-minute deflation of the angioplasty balloon. Primary end-point was infarct size (IS) reduction, expressed as percentage of left ventricle mass assessed by delayed enhancement on CMR at 30±10 days after index PPCI. RESULTS: All baseline characteristics but diabetes (p=0.06) were balanced between groups. Postconditioning patients trended toward a larger IS compared to those treated by standard PPCI (20±12% vs 14±10%, p=0.054). After exclusion of diabetics, PC group still showed a trend to larger IS (p=0.116). Major adverse events seem to be more frequent in PC group irrespective to diabetic status (p=0.053 and p=0.080, respectively). CONCLUSIONS: This prospective, randomized trial suggests that PC did not have the expected cardioprotective effect and on the contrary it might harm STEMI patients treated by PPCI plus abciximab. (Clinical Trial Registration-unique identifier: NCT01004289).