Effects of Diisodecyl Phthalate on PPAR:RXR-Dependent Expression Pathways in Sea Bream Hepatocytes

Evidence that endocrine-disrupting chemicals (EDCs) may target metabolic disturbances, beyond interference with the functions of the endocrine systems has recently accumulated. Among EDCs, phthalate plasticizers like the diisodecyl phthalate (DiDP) are commonly found contaminants of aquatic environments and have been suggested to function as obesogens by activating peroxisome proliferator activated receptors (PPARs), a subset of nuclear receptors (NRs) that act as metabolic sensors, playing pivotal roles in lipid homeostasis. However, little is known about the modulation of PPAR signaling pathways by DiDP in fish. In this study, we have first investigated the ligand binding efficiency of DiDP to the ligand binding domains of PPARs and retinoid-X-receptor-α (RXRα) proteins in fish using a molecular docking approach. Furthermore, in silico predictions were integrated by in vitro experiments to show possible dose-relationship effects of DiDP on PPAR:RXR-dependent gene expression pathways using sea bream hepatocytes. We observed that DiDP shows high binding efficiency with piscine PPARs demonstrating a greater preference for RXRα. Our studies also demonstrated the coordinate increased expression of PPARs and RXRα, as well as their downstream target genes in vitro. Principal component analysis (PCA) showed the strength of relationship between transcription of most genes involved in fatty acid metabolism and PPAR mRNA levels. In particular, fatty acid binding protein (FABP) was highly correlated to all PPARs. The results of this study suggest that DiDP can be considered an environmental stressor that activates PPAR:RXR signaling to promote long-term changes in lipid homeostasis leading to potential deleterious physiological consequences in teleost fish

Ghrelin induces apoptosis in colon adenocarcinoma cells via proteasome inhibition and autophagy induction.

Ghrelin is a metabolism-regulating hormone recently investigated for its role in cancer survival and progression. Controversially, ghrelin may act as either anti-apoptotic or pro-apoptotic factor in different cancer cells, suggesting that the effects are cell type dependent. Limited data are currently available on the effects exerted by ghrelin on intracellular proteolytic pathways in cancer. Both the lysosomal and the proteasomal systems are fundamental in cellular proliferation and apoptosis regulation. With the aim of exploring if the proteasome and autophagy may be possible targets of ghrelin in cancer, we exposed human colorectal adenocarcinoma cells to ghrelin. Preliminary in vitro fluorimetric assays evidenced for the first time a direct inhibition of 20S proteasomes by ghrelin, particularly evident for the trypsin-like activity. Moreover, 1 μM ghrelin induced apoptosis in colorectal adenocarcinoma cells by inhibiting the ubiquitin-proteasome system and by activating autophagy, with p53 having an "interactive" role

Acute shock efficacy of the subcutaneous implantable cardioverter-defibrillator according to the implantation technique

Background: The traditional technique for subcutaneous implantable cardioverter defibrillator (S-ICD) implantation involves three incisions and a subcutaneous (SC) pocket. An intermuscular (IM) 2-incision technique has been recently adopted. Aims: We assessed acute defibrillation efficacy (DE) of S-ICD (DE ≤65 J) according to the implantation technique. Methods: We analyzed consecutive patients who underwent S-ICD implantation and DE testing at 53 Italian centers. Regression analysis was used to determine the association between DFT and implantation technique. Results: A total of 805 patients were enrolled. Four groups were assessed: IM + 2 incisions (n = 546), SC + 2 incisions (n = 133), SC + 3 incisions (n = 111), and IM + 3 incisions (n = 15). DE was ≤65 J in 782 (97.1%) patients. Patients with DE ≤65 J showed a trend towards lower body mass index (25.1 vs. 26.5; p = .12), were less frequently on antiarrhythmic drugs (13% vs. 26%; p = .06) and more commonly underwent implantation with the 2-incision technique (85% vs. 70%; p = .04). The IM + 2-incision technique showed the lowest defibrillation failure rate (2.2%) and shock impedance (66 Ohm, interquartile range: 57-77). On multivariate analysis, the 2-incision technique was associated with a lower incidence of shock failure (hazard ratio: 0.305; 95% confidence interval: 0.102-0.907; p = .033). Shock impedance was lower with the IM than with the SC approach (66 vs. 70 Ohm p = .002) and with the 2-incision than the 3-incision technique (67 vs. 72 Ohm; p = .006). Conclusions: In a large population of S-ICD patients, we observed a high defibrillation success rate. The IM + 2-incision technique provides lower shock impedance and a higher likelihood of successful defibrillation

An Analysis of Italian Nurses’ Approach to Patients’ Pain: A Nationwide Online Survey

Healthcare providers play a fundamental role in evaluating pain. Several issues about how nurses are educated remain unsolved. The aim of our study was to address how Italian nurses manage patients suffering from pain in daily practice. A cross-sectional survey was administered among Italian registered nurses. Data were collected using a 34-item questionnaire that had been previously validated during a pilot study. The lowest level of participation/education/information events was observed in the South (p=0.0001). A significant difference among the four areas was found in the department affiliation of responders (p=0.0001). Pain assessment at patients’ admission was most frequent in the Northeast (32.9%), whereas the lowest frequency was found in the South (15.1%) (p=0.0001). The prevalence of nurses’ knowledge of pain scales and their distribution in usual applications was similar in the Northwest and -east, and Central Italy, but lower in the South (p=0.0001). This study underlines the need for change in the clinical approach to pain treatment in healthcare. Pain assessment is a fundamental step for preparing individualized therapeutic plans, and nurses play a crucial role in improving the quality of life of suffering patients

The Impact of Human Milk on Necrotizing Enterocolitis: A Systematic Review and Meta-Analysis

Background. Premature infants receiving breastfeed have a lower incidence of NEC than those fed preterm formula. This study aimed: (1) to update a systematic review and meta-analyses to evaluate the relationship between feeding and necrotizing enterocolitis (NEC) in low weight premature infants; (2) to conduct meta-regression analyses by subgroups; (3) to describe geographical distribution of milk banks in the world. Methods. Papers included in the meta-analysis were updated as of June 2019. Relative risks were used as a measure of effect size. Random effect models were used to account for different sources of variation among studies. For milk banks, the data reviewed by the literature were integrated with the information collected from countries’ institutional sites and milk bank networks. Results. Thirty-two papers were included in meta-analysis: six randomized controlled trials (RCTs) and 26 observational studies (OS). The census has found 572 milk banks around in the world. Brazil has the most active milk banks. RCTs meta-analysis indicates a risk reduction of NEC using human milk respect to formula: Relative risk (RR) = 0.62 (0.42–0.93). Seven OS compared quantities lower than human milk or higher than the 50th quantile showing a risk reduction of NEC:RR = 0.51 (0.31–0.85); 3 OS that evaluated human milk versus mixed feeding showing that human milk has a protective role on the development of NEC:RR = 0.74 (0.63–0.91). Results of subgroups analysis show that the risk reduction is statistically significant only for studies in which premature infants are given both their own and donated breastmilk. Conclusions. The possibility of preserving human milk and promoting donations guarantees an improvement in the health of newborns

HtrA1: Its future potential as a novel biomarker for cancer

HtrA1 appears to be involved in several physiological processes as well as in the pathogenesis of conditions such as Alzheimer’s disease and osteoarthritis. It has also been hypothesized to play a role as a tumor suppressor. This manuscript reviews the current cancer-related HtrA1 research from the methodological and clinical standpoints including studies regarding its potential role as a tumor marker and/or prognostic factor. PRISMA method was used for study selection. The articles thus collected were examined and selected by two independent reviewers; any disagreement was resolved by a methodologist. A laboratory researcher reviewed the methods and laboratory techniques. Fifteen studies met the inclusion criteria and concerned the following cancer sites: the nervous system, bladder, breast, esophagus, stomach, liver, endometrium, thyroid, ovaries, pleura, lung and skin. Most articles described in vivo studies using a morphological approach and immunohistochemistry, whereas protein expression was quantified as staining intensity scored by two raters. Often the results were not comparable due to the different rating scales and study design. Current research on HtrA1 does not conclusively support its role as a tumor suppressor

The Effects of the Ukrainian Conflict on Oncological Care: The Latest State of the Art

Background: The COVID-19 pandemic has dramatically affected all aspects of the patient’s pathway to cancer diagnosis and subsequent treatment. Our main objective was to evaluate the status of cancer trials in Ukraine as of September 2022. Methods: Initially, we examined with a narrative review the state of breast, colorectal, and cervical cancer population-based screening. Subsequently, we assessed each trial status for the years 2021 and 2022. Results: Estimates of participation in breast and cervical cancer screening are different from region to region. Moreover, regarding cervical cancer screening, extremely different participation estimates were reported: 73% in 2003 vs. <10% 2020. Our data show that from 2014 to 2020, despite the pandemic, cancer trials in Ukraine significantly increased from 27 to 44. In 2021 no trials were completed; in fact, we observed that out of 41 trials, 8 were active not recruiting, 33 were recruiting, and 0 were completed or terminated. In 2022 in Ukraine, for oncological pathologies, only 3 trials were registered, while in 2021, 41 trials were registered. The suspension of trials regarded above all concern hematological tissue (66.7%) and the genitourinary tract (60%). Conclusions: Our work has highlighted how the areas most affected by the conflict present criticalities in oncological care

Abdominal Aortic Screening Is a Priority for Health in Smoker Males: A Study on Central Italian Population

Abdominal aortic aneurysm (AAA) is a major public health problem. In the last decade, in some European countries, abdominal aortic screening (AAS) is emerging as a potential prevention for the rupture of AAA. The goals of our study were to estimate AAA prevalence and risk factors in males and females in a central Italian population, also defining the cost-effectiveness of AAS programs. A pilot study screening was conducted between 1 January 2015 and 31 December 2019 in the municipality of Teramo (Abruzzo Region, Italy) in a group of men and women, ranging from the age of 65 to 79, who were not previously operated on for AAA. The ultrasound was performed by means of Acuson sequoia 512 Simens with a Convex probe. The anterior posterior of the infra-renal aorta was evaluated. The odds ratio values (ORs) were used to evaluate the risk of AAA, and the following determinants were taken into consideration: gender, smoke use, hypertension, and ischemic heart disease. We also estimated the direct costs coming from aneurysmectomy (surgical repair or endovascular aneurysms repair—EVAR). A total of 62 AAA (2.7%, mean age 73.8 ± 4.0) were diagnosed, of which 57 were in men (3.7%, mean age 73.6 ± 4.0) and 5 were in women (0.7%, mean age 74.3 ± 4.1). Male gender and smoke use are more important risk factors for AAA ≥ 3 cm, respectively: OR = 5.94 (2.37–14.99, p < 0.001) and OR = 5.21 (2.63–10.30, p < 0.000). A significant increase in OR was noted for AAA ≥ 3 cm and cardiac arrhythmia and ischemic heart disease, respectively: OR = 2.81 (1.53–5.15, p < 0.000) and OR = 2.76 (1.40–5.43, p = 0.006). Regarding the cost analysis, it appears that screening has contributed to the reduction in costs related to urgency. In fact, the synthetic indicator given by the ratio between the DRGs (disease related group) relating to the emergency and those of the elective activity went from 1.69 in the year prior to the activation of the screening to a median of 0.39 for the five-year period of activation of the screening. It is important to underline that the results of our work confirm that the screening activated in our territory has led to a reduction in the expenditure for AAA emergency interventions, having increased the planned interventions. This must be a warning for local stakeholders, especially in the post-pandemic period, in order to strengthen prevention

Lifestyle Risk Factors for Type 2 Diabetes Mellitus and National Diabetes Care Systems in European Countries

Background. Diabetes is increasing by 3.09% per year in males and 1.92% in females. Lifestyle risk factors are related to diabetes. The aim of this work is to highlight within EU-28 countries the distribution percentages of some lifestyle risk factors and some components of diabetes health care. Methods. A literature search was conducted to highlight the presence of diabetes registries, which are fundamental tools for disease surveillance and health planning; the presence of a national diabetes plan (NDP); the care setting; and methods used for reimbursement of drugs, devices, and coverage of any comorbidities associated with diabetes. A multiple correspondence analysis (MCA) was carried out to evaluate the possible associations between the variables considered. Results. The highest percentages of diabetes (>10%) are registered in Bulgaria, Malta, and Hungary. Concerning the prevalence of overweight, no European country shows overall percentages of less than 50%. Regarding obesity, 57% of countries show prevalence rates of 25%. The record for physical inactivity belongs to Malta, with 45% of individuals being inactive. The percentage of physical inactivity for females is higher than for males across Europe. In total, 57% of the countries have an insurance-based health system, while 12 countries have public national health systems. Further, 57% of countries have an NDP, while 42% of the EU countries have established a prevalence register for diabetes. Conclusions. Prevalence rates for type 2 DM in the range of 8–9% are noted in 50% of EU-28 countries. In total, 21 out of EU countries show a high prevalence rate for overweight, while 7% of EU-28 countries have an obesity prevalence rate of 25%. Diabetes treatment is entrusted to general practitioners in most countries. The results of this work highlight the differences between countries, but also between genders