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Obesity, whose prevalence is pandemic and continuing to increase, is a major preventable and modifiable risk factor for diabetes and cardiovascular diseases, as well as for cancer. Furthermore, epidemiological studies have shown that obesity is a negative independent prognostic factor for several oncological outcomes, including overall and cancer-specific survival, for several site-specific cancers as well as for all cancers combined. Yet, a recently growing body of evidence suggests that sometimes overweight and obesity may associate with better outcomes, and that immunotherapy may show improved response among obese patients compared with patients with a normal weight. The so-called ‘obesity paradox’ has been reported in several advanced cancer as well as in other diseases, albeit the mechanisms behind this unexpected relationship are still not clear. Aim of this review is to explore the expected as well as the paradoxical relationship between obesity and cancer prognosis, with a particular emphasis on the effects of cancer therapies in obese people.

I4.0 revolution is permeating every technical sector, by promoting deployment of enabling technologies (ETs), also in the facility management (FM) discipline. As FM regards the integration of processes within an organization to support activities, it is clear how ETs can trigger, in the FM area, significant innovations like a better failure knowledge management and a sustainable use of resources. More specifically, the implementation in building maintenance of dynamic systems, linked to sensors networks, can allow changes into knowledge management and FM decision-making processes. Starting from these premises, the paper deals with an ongoing research, whose aim is to investigate how ETs may innovate the traditional maintenance strategies with new approaches in corrective, condition-based and predetermined maintenance. According to the above, building maintenance, which is traditionally reactive, may actually become proactive if failure management policy is set. The aim of this paper is to demonstrate how ETs adoption may promote innovation in FM processes focusing on maintenance in service equipment field. More specifically, an operative and methodological framework for reaching proactive maintenance is described through the support of a case study concerning two major healthcare infrastructures in Italy, managed by a major FM company.

Cocaine and ethanol (EtOH) co-consumption is a risk factor for physiologically and clinically negative outcomes. We describe the occurrence of cocaine consumption alone or co-consumption with EtOH and others psychotropics. The descriptive research used data on medical records of patients positive to cocaine test who attended an emergency room between 2016 and 2017. We determined the frequency of cocaine consumption alone and co-consumption with EtOH, cannabis or benzodiazepines (BZDs). Over one year period, 88 patients (13.3%) were positive to cocaine test, mainly attended on weekends, in holiday months, young adults or men. Among those positive for cocaine, 72% were also positive for EtOH, cannabis or BZD. Cocaine co-consumption with one or two out of three substance was 55.2% (CI95%; 44.7-65.8%) and 16.4% (CI95%;8.58-24.3%), respectively. Co-consumption was more frecuently wih EtOH, followed by cannabis or BZD. Co-consumption of cocaine with EtOH is very common and could be associated with acute or chronic consumption of cannabis or acute exposure to BZDs. It is important that emergency physicians use a systematic approach to diagnose and treat more than one psychotropic substance in cocaine positive patients.

Catechins are able to modulate the gelatinolytic activity of matrix metalloproteinase-9 (MMP-9) by reducing its release from macrophages. Gallocatechins decrease MMP-9 secretion by lowering MMP-9 promoter activity and mRNA levels. The effect appears to be dependent on some structural and stereochemical requirements. In this study, the relationship between chemical structure and activity was studied by testing the effect of analogues of (+/-)-gallocatechin-3-gallate (+/-)-GCG, selectively deprived of hydroxyl groups, on MMP-9 activity, transcription, and secretion. Our results indicate that (+/-)-GCG and (+/-)-catechin-3-gallate are characterized by a substitution pattern compatible with direct inhibition of MMP-9 activity. Conversely, when transcription was the target, (+/-)-trans-3-flavanol-3-benzoate, lacking all the hydroxyl groups, was the most effective both in lowering MMP-9 promoter activity and consequently protein secretion, and in inhibiting nuclear-factor-kappaB-driven transcription. Our results suggest that the structural requirements for enzyme inhibition are different from those necessary for targeting gene expression.

Investigations of self-acceptance are critical to understanding the development and maintenance of psychological health. However, valid and reliable instruments for measuring self-acceptance in persons with early blindness have yet to be developed. The current research describes three studies designed to develop and validate the Self-acceptance Scale for Persons with Early Blindness (SAS-EB). In Study 1, we developed the initial item pool. Thirty-three items were generated, based on data from specialized literature and from 2 focus groups. Items were organized in a three-factor structure, theoretically predicted for SAS-EB - (1) body acceptance, (2) self-protection from social stigmas, and (3) feeling and believing in one's capacities. In Study 2, information obtained from a panel of 9 experts and 22 persons with early blindness representing the target population was used to refine the initial item pool, generating a new pool of 27 items. In Study 3, 318 persons with early blindness (141 women and 177 men), between 18 and 60 years of age (M = 37.74 years, SD = 12.37) answered the new pool of 27 items. After the elimination of 9 items using confirmatory factor analysis, we confirmed the theoretical three-factor structure of the SAS-EB. Study 3 also provided support for the scale's internal consistency and construct validity. Finally, the psychometric properties of the SAS-EB, its utility, and its limitations are discussed along with considerations for future research.

Medium rings (8-12 atoms) are present in many naturally occurring molecules which in many cases have potentially useful biological activity. Unfortunately current synthetic methods to synthesise medium rings lack general applicability or require high dilution and/or tedious optimisation procedures. This thesis describes the investigation of a novel strategy in which a suitably functionalised linear precursor undergoes double cyclisation and fragmentation to afford a medium ring. The key to this proposed sequence is the generation of an intramolecular cyclic ylide which can react with a pendant electrophile generating a bicyclic intermediate that subsequently undergoes fragmentation, thus generating a medium ring. The use of sulfur ylides was initially investigated for the synthesis of the 8-membered ring natural product Cephalosporolide-D but all attempts to trigger the proposed sequence of events were unsuccessful leading only to side reactions or decomposition. Alternative metal catalysed approaches to the synthesis of sulfur ylides were also investigated with no success. Nitrogen and phosphorus cyclic ylides were also evaluated and the latter reaction gave small quantities of the target medium ring product. This thesis also describes the discovery that high levels of diastereoselectivity could be achieved by the addition of carbon-nucleophiles to α-sulfenylaldehydes, intermediates in the synthesis of precursors to medium rings. Enantiomerically enriched secondary alcohols could be subsequently obtained from the β-hydroxysulfides after Raney-Ni reduction of the carbon-sulfur bond. In combination with the studies on metal catalysed generation of ylides, this thesis reports a gold(I) catalysed mild procedure for the synthesis of haloalkynes from either terminal alkynes or trimethylsilylacetylenes initially discovered in our laboratories. Interestingly it was found that protic acids were able to catalyse the halogenation of trimethylsilylacetylenes but not of terminal alkynes. The reactions were successfully extended to a series of aromatic and aliphatic alkynes. Procedures were also developed for the conversions of terminal alkynes into α-iodoketones which were also used in situ for the synthesis of heterocycles.

Medium rings (8-12 atoms) are present in many naturally occurring molecules which in many cases have potentially useful biological activity. Unfortunately current synthetic methods to synthesise medium rings lack general applicability or require high dilution and/or tedious optimisation procedures. This thesis describes the investigation of a novel strategy in which a suitably functionalised linear precursor undergoes double cyclisation and fragmentation to afford a medium ring. The key to this proposed sequence is the generation of an intramolecular cyclic ylide which can react with a pendant electrophile generating a bicyclic intermediate that subsequently undergoes fragmentation, thus generating a medium ring. The use of sulfur ylides was initially investigated for the synthesis of the 8-membered ring natural product Cephalosporolide-D but all attempts to trigger the proposed sequence of events were unsuccessful leading only to side reactions or decomposition. Alternative metal catalysed approaches to the synthesis of sulfur ylides were also investigated with no success. Nitrogen and phosphorus cyclic ylides were also evaluated and the latter reaction gave small quantities of the target medium ring product. This thesis also describes the discovery that high levels of diastereoselectivity could be achieved by the addition of carbon-nucleophiles to α-sulfenylaldehydes, intermediates in the synthesis of precursors to medium rings. Enantiomerically enriched secondary alcohols could be subsequently obtained from the β-hydroxysulfides after Raney-Ni reduction of the carbon-sulfur bond. In combination with the studies on metal catalysed generation of ylides, this thesis reports a gold(I) catalysed mild procedure for the synthesis of haloalkynes from either terminal alkynes or trimethylsilylacetylenes initially discovered in our laboratories. Interestingly it was found that protic acids were able to catalyse the halogenation of trimethylsilylacetylenes but not of terminal alkynes. The reactions were successfully extended to a series of aromatic and aliphatic alkynes. Procedures were also developed for the conversions of terminal alkynes into α-iodoketones which were also used in situ for the synthesis of heterocycles.

To evaluate the current staging system of lung cancer, taking into account different selection criteria for the studied population. A total of 2,991 consecutive patients with surgical lung cancer were prospectively compiled from 19 Spanish hospitals (Bronchogenic Carcinoma Cooperative Group of the Spanish Society of Pneumology and Thoracic Surgery) between 1993 and 1997. The Kaplan-Meier method was used to calculate survival at 5 years (S5) for each pathologic stage, and the log-rank test was used for comparison purposes. These studies were performed in the total group (population 1, n = 2,972); excluding operative mortality and small cell lung cancer cases (population 2, n = 2,697); excluding cases with induction therapy (population 3, n = 2,542); excluding cases with exploratory thoracotomy (population 4, n = 2,304); and, lastly, excluding cases with incomplete resection (population 5, n = 2082) [70% of the initial population]. The global S5 was similar in populations 1, 2, and 3: 34% (95% confidence interval [CI] 32 to 36%), 37% (95% CI, 35 to 39%), and 38% (95% CI, 35 to 39%), but different from that of populations 4 and 5: 40% (95% CI, 39 to 43%) and 43% (41 to 45%), respectively. For pathologic stage I, pathologic stage II, and pathologic state IIIA (pIIIA), S5 was similar in the five reported populations. In pathologic stage IIIB (pIIIB), there were differences in S5 between populations 1, 2, and 3 (13 to 15%; 95% CI, 10 to 19%) and populations 4 and 5 (26 to 29%; 95% CI, 19 to 38%). In population 4, there was no significant prognostic difference between two specific stage groups, that is between pathologic stage IB (pIB) and pathologic state IIA (pIIA) [p = 0.70] and between pIIIA and pIIIB (p = 0.79); the pathologic T3N2M0 combination has a S5 (13%) lower than that for pIIIB (26%). The definition of the population that constitutes the denominator for the analysis of survival in surgical lung cancer is important in pIIIB. The inclusion or exclusion of cases without resection is the most important factor for the selection of such population. This study detected that there are no prognostic differences between pIB and pIIA, and between pIIIA and pIIIB.