Targeted therapies by means of compounds that inhibit a specific target molecule represent a new perspective in the treatment of cancer. In contrast to conventional chemotherapy which acts on all ...dividing cells generating toxic effects and damage of normal tissues, targeted drugs allow to hit, in a more specific manner, subpopulations of cells directly involved in tumor progression. Molecules controlling cell proliferation and death, such as Tyrosine Kinase Receptors (RTKs) for growth factors, are among the best targets for this type of therapeutic approach. Two classes of compounds targeting RTKs are currently used in clinical practice: monoclonal antibodies and tyrosine kinase inhibitors. The era of targeted therapy began with the approval of Trastuzumab, a monoclonal antibody against HER2, for treatment of metastatic breast cancer, and Imatinib, a small tyrosine kinase inhibitor targeting BCR-Abl, in Chronic Myeloid Leukemia. Despite the initial enthusiasm for the efficacy of these treatments, clinicians had to face soon the problem of relapse, as almost invariably cancer patients developed drug resistance, often due to the activation of alternative RTKs pathways. In this view, the rationale at the basis of targeting drugs is radically shifting. In the past, the main effort was aimed at developing highly specific inhibitors acting on single RTKs. Now, there is a general agreement that molecules interfering simultaneously with multiple RTKs might be more effective than single target agents. With the recent approval by FDA of Sorafenib and Sunitinib - targeting VEGFR, PDGFR, FLT-3 and c-Kit - a different scenario has been emerging, where a new generation of anti-cancer drugs, able to inhibit more than one pathway, would probably play a major role.
Objective: The influence of postprandial blood glucose on diabetes complications is intensively debated. We aimed to evaluate the predictive role of both fasting and postprandial blood glucose on ...cardiovascular events in type 2 diabetes and the influence of gender.
Methods: In a population of 529 (284 men and 245 women) consecutive type 2 diabetic patients attending our diabetes clinic, we evaluated the relationships, corrected for cardiovascular risk factors and type of treatment, between cardiovascular events in a 5-yr follow-up and baseline values of hemoglobin A1c (HbA1c) and blood glucose measured: 1) after an overnight fast, 2) after breakfast, 3) after lunch, and 4) before dinner. Continuous variables were categorized into tertiles.
Results: We recorded cardiovascular events in 77 subjects: 54 of 284 men (19%) and 23 of 245 women (9.4%). Univariate analysis indicated that cardiovascular events were associated with increasing age, longer diabetes duration, and higher HbA1c and fibrinogen in men, and higher systolic blood pressure, albumin excretion rate, HbA1c, and all blood glucose values in women. Smoking was more frequent in subjects with events. When all blood glucose values and HbA1c were introduced simultaneously in the models, only blood glucose after lunch predicted cardiovascular events, with hazard ratio of the third tertile vs. the first and the second tertiles greater in women (5.54; confidence interval, 1.45–21.20) than in men (2.12; confidence interval, 1.04–4.32; P < 0.01).
Conclusions: Postprandial, but not fasting, blood glucose is an independent risk factor for cardiovascular events in type 2 diabetes, with a stronger predictive power in women than in men, suggesting that more attention should be paid to postprandial hyperglycemia, particularly in women.
Background and purpose
Patients with Parkinson's disease (PD) are at high risk for cognitive dysfunction. Non‐pharmacological interventions have attracted increasing interest for enhancing PD ...patients' cognitive functions.
Methods
One‐year follow‐up data (T2) of a randomized controlled trial evaluating two 6‐week cognitive trainings – a structured (NEUROvitalis, NV) and an unstructured (mentally fit, MF) program − compared with a waiting list control group (CG) in non‐demented PD patients (Hoehn and Yahr I–III) are presented. Forty‐seven PD patients were examined at T2. Effects on overall cognitive functions (Mini‐Mental State Examination and DemTect) were compared between all groups with repeated measurement analyses of variance. A combined score of the percentage change value from baseline (T0) to T2 was calculated to identify patients who retained or improved their cognitive state (responders). The risk of developing mild cognitive impairment (MCI) was analyzed.
Results
Significant time × treatment effects on overall cognitive functions were found for both training groups, each compared separately to the CG (DemTect, P < 0.05). Nine patients (56.3%) of the NV group, seven (41.2%) of the MF group and three (21.4%) of the CG were responders. Comparing NV to CG the odds ratio was 4.7 95% confidence interval (0.8; 33.3), and comparing MF to CG it was 2.6 95% confidence interval (0.4; 17.4). MCI risk for patients without prior MCI was 40.0% in CG, 18.2% in MF and 18.2% in NV. The odds ratio was 3 comparing NV to CG, MF to CG.
Discussion
This study gives evidence that cognitive training may be effective to prevent cognitive decline and onset of MCI in PD patients.
•A thiol function was readily introduced to the reducing-end of oligosaccharides.•Oligosaccharide-b-polystyrene were prepared by metal-free thiol–maleimide addition.•Amphiphilic OBCPs self-assembled ...in water into spherical nanoparticles.
Amphiphilic oligosaccharide-based block copolymers (OBCPs) are able to self-assemble either into nanoparticles with biocompatible oligosaccharides corona in aqueous solution or in sub-nanopatterned thin-films originating from the high incompatibility between the different blocks. For these reasons, these biosourced OBCPs are valuable structures for applications in nanomedicine and nanoelectronics. Up to now, the synthesis of those OBCPs was obtained through grafting-onto method using Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC). However, complete removal of metal catalyst residues from the resultant copolymer chains is critical and hampers electronic and biomedical applications. In this study, we report an efficient and convenient metal-free click chemistry approach consisting in coupling thiol-containing oligosaccharide blocks to maleimide-terminated polystyrenes. Upon self-assembly in water, spherical micelles of similar size than those obtained by Cu(I)-catalyzed azide–alkyne cycloaddition were formed as evidenced using dynamic light scattering and transmission electron microscopy techniques.
MicroRNAs (miRNAs) have an important role in a wide range of physiological and pathological processes, and their dysregulation has been reported to affect the development and progression of cancers, ...including hepatocellular carcinoma (HCC). However, in the plethora of dysregulated miRNAs, it is largely unknown which of them have a causative role in the hepatocarcinogenic process. In the present study, we first aimed to determine changes in the expression profile of miRNAs in human HCCs and to compare them with liver tumors generated in a rat model of chemically induced HCC. We found that members of the miR-100 family (miR-100, miR-99a) were downregulated in human HCCs; a similar downregulation was also observed in rat HCCs. Their reduction was paralleled by an increased expression of polo like kinase 1 (PLK1), a target of these miRNAs. The introduction of miR-100 in HCC cells impaired their growth ability and their capability to form colonies in soft agar. Next, we aimed at investigating, in the same animal model, if dysregulation of miR-100 and PLK1 is an early or late event along the multistep process of hepatocarcinogenesis. The obtained results showed that miR-100 downregulation (i) is already evident in very early preneoplastic lesions generated 9 weeks after carcinogenic treatment; (ii) is also observed in adenomas and early HCCs; and (iii) is not simply a marker of proliferating hepatocytes. To our knowledge, this is the first work unveiling the role of a miRNA family along HCC progression.
This study was to compare the incidence and clinical outcomes of SARS-CoV-2 infection between Italian and non-Italian nationals.
We retrospectively analysed data from the COVID-19 Italian integrated ...surveillance system (14 September 2020 to 17 October 2021).
We used multivariable Cox proportional hazards models to estimate the hazard ratio (HR) of infection and, among cases, the HRs of death, hospitalisation and subsequent admission to intensive care unit in non-Italian nationals relative to Italian nationals. Estimates were adjusted for differences in sociodemographic characteristics and in the week and region of diagnosis.
Of 4,111,067 notified cases, 336,265 (8.2%) were non-Italian nationals. Compared with Italian nationals, non-Italians showed a lower incidence of SARS-CoV-2 infection (HR = 0.81, 95% confidence interval CI: 0.80–0.81). However, once diagnosed, they were more likely to be hospitalised (HR = 1.90, 95% CI: 1.87–1.92) and then admitted to intensive care unit (HR = 1.08, 95% CI: 1.04–1.13), with differences larger in those coming from countries with a lower human development index. Compared with Italian cases, an increased rate of death was observed in non-Italian cases from low–human development index countries (HR = 1.41, 95% CI: 1.23–1.62). The HRs of SARS-CoV-2 infection and severe outcomes slightly increased after the start of the vaccination campaign.
Underdiagnosis and delayed diagnosis in non-Italian nationals could explain their lower incidence compared with Italians and, among cases, their higher probability to present clinical conditions leading to worse outcomes. Facilitating early access to vaccination, diagnosis and treatment would improve the control of SARS-CoV-2 transmission and health outcomes in this vulnerable group.
Country of origin might affect vaccine uptake in children born to immigrants. We aimed to evaluate differences in childhood vaccination coverage (VC) and timeliness by macro-area of origin of foreign ...mothers residing in Italy.
Multicentre retrospective birth cohorts.
We analysed data of 23,287 children born in 2009–2014 to foreign women in the cities of Rome, Turin and Treviso. We retrieved data through record-linkage of the population, vaccination and birth registries. We estimated VCs at different ages for vaccines against tetanus, measles and meningococcal group-C, using the Kaplan–Meier method. Factors associated with vaccine uptake were evaluated using multilevel Poisson models.
Estimates of VC at any age and for all antigens were significantly lower in children born to women from Asia and higher in children born to women from Africa, as compared to other macro-areas. Similar differences by area of origin were observed for timeliness; independently of mother's sociodemographic characteristics and neonatal outcomes, the probability of delay vaccination after 2 years of age for each antigen was highest in children born to women from Asia. The risk of missed vaccination for all antigens was significantly higher in children born to younger and unemployed women.
Factors related to area of origin (e.g., cultural habits, language skills) are likely to affect parents’ decision to vaccinate their children. These factors, as well as sociodemographic characteristics, should be adequately investigated and addressed to increase vaccine uptake in foreign children, especially those born to Asian women.
Data on gender-specific profiles of cognitive functions in patients with Parkinson's disease (PD) are rare and inconsistent, and possible disease-confounding factors have been insufficiently ...considered.
The LANDSCAPE study on cognition in PD enrolled 656 PD patients (267 without cognitive impairment, 66% male; 292 with mild cognitive impairment, 69% male; 97 with PD dementia, 69% male). Raw values and age-, education-, and gender-corrected Z scores of a neuropsychological test battery (CERAD-Plus) were compared between genders. Motor symptoms, disease duration, l-dopa equivalent daily dose, depression - and additionally age and education for the raw value analysis - were taken as covariates.
Raw-score analysis replicated results of previous studies in that female PD patients were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.03), while men outperformed women in visuoconstruction (p = 0.002) and figural memory (p = 0.005). In contrast, gender-corrected Z scores showed that men were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.02; recognition, p = 0.04), while no difference was found for visuospatial tests. This picture could be observed both in the overall analysis of PD patients as well as in a differentiated group analysis.
Normative data corrected for gender and other sociodemographic variables are relevant, since they may elucidate a markedly different cognitive profile compared to raw scores. Our study also suggests that verbal memory decline is stronger in women than in men with PD. Future studies are needed to replicate these findings, examine the progression of gender-specific cognitive decline in PD and define different underlying mechanisms of this dysfunction.
Improvements in functional endoscopic sinus surgery (FESS) and computed tomography (CT) have concurrently increased interest in the anatomy of the paranasal region. Common anatomical variations are ...not rare in patients with chronic paranasal sinusitis. The aim of this retrospective study was to analyze the incidence of anatomic variations of the lateral nasal wall in a series of 200 patients with persistent symptoms of rhinosinusitis, after failure of medical therapies, and their correlation with paranasal sinus disease. A detailed analysis of CT scans showed that 140 of 200 (70%) patients had anatomic variations. In particular, 122 patients (87%) were affected by common anatomic variations, and 18 patients (13%) with uncommon variations. There were 85 (60.7%) male and 55 (39.3%) females with ages ranging from 13 to 77 years (mean 45.5 years). The maxillary sinus was most commonly involved, followed by the anterior ethmoid, frontal sinus, posterior ethmoid and sphenoid sinus. Statistically significant association was found between the presence of common anatomic variations - septal deviation, bilateral concha bullosa, medial deviation of uncinate process, Haller cell, ethmoidal bulla hypertrophic, agger nasi cell - and the presence of sinus mucosal disease (p < 0.05). There was no significant correlation between other common and uncommon anatomic variations and mucosal pathologies. The associations were evaluated using the Fisher's exact test, and compared with those reported in the literature. Considering the results obtained, we believe that some anatomic variations may increase the risk of sinus mucosal disease. We therefore emphasize the importance of a careful evaluation of CT study in patients with persistent symptoms and recurrent chronic rhinosinusitis in order to identify those with anatomical variations that may have an increased risk of developing rhinosinusitis.
Abstract Background and aims We compared direct costs of diabetic and non diabetic people covered by the Italian National Health System, focusing on the influence of age, sex, type of diabetes and ...treatment. Methods and results Diabetic people living in Turin were identified through the Regional Diabetes Registry and the files of hospital discharges and prescriptions. Data sources were linked to the administrative databases to assess health care services used by diabetic ( n = 33,792) and non diabetic people( n = 863,123). Data were analyzed with the two-part model; the estimated direct costs per person/year were €3660.8 in diabetic people and €895.6 in non diabetic people, giving a cost ratio of 4.1. Diabetes accounted for 11.4% of total health care expenditure. The costs were attributed to hospitalizations (57.2%), drugs (25.6%), to outpatient care (11.9%), consumable goods (4.4%) and emergency care (0.9%). Estimated costs increased from € 2670.8 in diabetic people aged <45 years to € 3724.1 in those aged >74 years, the latter representing two third of the diabetic cohort; corresponding figures in non diabetic people were € 371.6 and € 2155.9. In all expenditure categories cost ratios of diabetic vs non diabetic people were higher in people aged <45 years, in type 1 diabetes and in insulin-treated type 2 diabetes. Conclusion Direct costs are 4-fold higher in diabetic than in non diabetic people, mainly due to care of the elderly and inpatient care. In developed countries, demographic changes will have a profound impact on costs for diabetes in next years.
PDF
