Structural basis for DNA binding specificity by the auxin-dependent ARF transcription factors.

Auxin regulates numerous plant developmental processes by controlling gene expression via a family of functionally distinct DNA-binding auxin response factors (ARFs), yet the mechanistic basis for generating specificity in auxin response is unknown. Here, we address this question by solving high-resolution crystal structures of the pivotal Arabidopsis developmental regulator ARF5/MONOPTEROS (MP), its divergent paralog ARF1, and a complex of ARF1 and a generic auxin response DNA element (AuxRE). We show that ARF DNA-binding domains also homodimerize to generate cooperative DNA binding, which is critical for in vivo ARF5/MP function. Strikingly, DNA-contacting residues are conserved between ARFs, and we discover that monomers have the same intrinsic specificity. ARF1 and ARF5 homodimers, however, differ in spacing tolerated between binding sites. Our data identify the DNA-binding domain as an ARF dimerization domain, suggest that ARF dimers bind complex sites as molecular calipers with ARF-specific spacing preference, and provide an atomic-scale mechanistic model for specificity in auxin response.

Gapped Collective Charge Excitations and Interlayer Hopping in Cuprate Superconductors.

We use resonant inelastic x-ray scattering to probe the propagation of plasmons in the electron-doped cuprate superconductor Sr_{0.9}La_{0.1}CuO_{2}. We detect a plasmon gap of ∼120 meV at the two-dimensional Brillouin zone center, indicating that low-energy plasmons in Sr_{0.9}La_{0.1}CuO_{2} are not strictly acoustic. The plasmon dispersion, including the gap, is accurately captured by layered t-J-V model calculations. A similar analysis performed on recent resonant inelastic x-ray scattering data from other cuprates suggests that the plasmon gap is generic and its size is related to the magnitude of the interlayer hopping t_{z}. Our work signifies the three dimensionality of the charge dynamics in layered cuprates and provides a new method to determine t_{z}.

Differences in the incidence and clinical outcomes of SARS-CoV-2 infection between Italian and non-Italian nationals using routine data.

OBJECTIVES: This study was to compare the incidence and clinical outcomes of SARS-CoV-2 infection between Italian and non-Italian nationals. STUDY DESIGN: We retrospectively analysed data from the COVID-19 Italian integrated surveillance system (14 September 2020 to 17 October 2021). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Patients with Lemierre syndrome have a high risk of new thromboembolic complications, clinical sequelae and death: an analysis of 712 cases.

BACKGROUND: Lemierre syndrome is characterized by head/neck vein thrombosis and septic embolism usually complicating an acute oropharyngeal bacterial infection in adolescents and young adults. We described the course of Lemierre syndrome in the contemporary era. METHODS: In our individual-level analysis of 712 patients (2000-2017), we included cases described as Lemierre syndrome if these criteria were met: (i) primary site of bacterial infection in the head/neck; (ii) objectively confirmed local thrombotic complications or septic embolism. The study outcomes were new or recurrent venous thromboembolism or peripheral septic lesions, major bleeding, all-cause death and clinical sequelae. RESULTS: The median age was 21 (Q1-Q3: 17-33) years, and 295 (41%) were female. At diagnosis, acute thrombosis of head/neck veins was detected in 597 (84%) patients, septic embolism in 582 (82%) and both in 468 (80%). After diagnosis and during in-hospital follow-up, new venous thromboembolism occurred in 34 (5.2%, 95% CI 3.8-7.2%) patients, new peripheral septic lesions became evident in 76 (11.7%; 9.4-14.3%). The rate of either was lower in patients who received anticoagulation (OR: 0.59; 0.36-0.94), higher in those with initial intracranial involvement (OR: 2.35; 1.45-3.80). Major bleeding occurred in 19 patients (2.9%; 1.9-4.5%), and 26 died (4.0%; 2.7-5.8%). Clinical sequelae were reported in 65 (10.4%, 8.2-13.0%) individuals, often consisting of cranial nerve palsy (n = 24) and orthopaedic limitations (n = 19). CONCLUSIONS: Patients with Lemierre syndrome were characterized by a substantial risk of new thromboembolic complications and death. This risk was higher in the presence of initial intracranial involvement. One-tenth of survivors suffered major clinical sequelae.

The Arabidopsis Leucine-Rich Repeat Receptor Kinase BIR3 Negatively Regulates BAK1 Receptor Complex Formation and Stabilizes BAK1.

BAK1 is a coreceptor and positive regulator of multiple ligand binding leucine-rich repeat receptor kinases (LRR-RKs) and is involved in brassinosteroid (BR)-dependent growth and development, innate immunity, and cell death control. The BAK1-interacting LRR-RKs BIR2 and BIR3 were previously identified by proteomics analyses of in vivo BAK1 complexes. Here, we show that BAK1-related pathways such as innate immunity and cell death control are affected by BIR3 in Arabidopsis thaliana BIR3 also has a strong negative impact on BR signaling. BIR3 directly interacts with the BR receptor BRI1 and other ligand binding receptors and negatively regulates BR signaling by competitive inhibition of BRI1. BIR3 is released from BAK1 and BRI1 after ligand exposure and directly affects the formation of BAK1 complexes with BRI1 or FLAGELLIN SENSING2. Double mutants of bak1 and bir3 show spontaneous cell death and constitutive activation of defense responses. BAK1 and its closest homolog BKK1 interact with and are stabilized by BIR3, suggesting that bak1 bir3 double mutants mimic the spontaneous cell death phenotype observed in bak1 bkk1 mutants via destabilization of BIR3 target proteins. Our results provide evidence for a negative regulatory mechanism for BAK1 receptor complexes in which BIR3 interacts with BAK1 and inhibits ligand binding receptors to prevent BAK1 receptor complex formation.

Demolition activities in a healthcare facility: results from a fungal surveillance after extraordinary preventive measures.

OBJECTIVES: Aspergillus spp could be responsible of nosocomial aspergillosis in immunocompromised patients. In 2018, it was decided to demolish a building of Careggi Hospital (Florence, Italy), the Chief Medical Officer ordered a 9-months-long air and surface microbiological sampling and extraordinary preventive measures. STUDY DESIGN: A 9-months-long prospective study. METHODS: After mapping the at-risk areas, air and surface samples were collected in different locations: in corridors, in rooms (high efficiency particulate air filter (HEPA) filtered or not), and outdoors. The samples were collected during the critical phases of the demolition. Air temperature and weather conditions were determined and recorded at the beginning of each sampling. RESULTS: Seventy-eight air samples and 72 surface samples were collected. The results showed highest contamination at time zero (before extraordinary preventive measures) and in the wards without HEPA filtered air. No specific prophylaxis strategy was implemented at our hospital for immunocompromised patients, and no cases of aspergillosis were recorded. CONCLUSIONS: Our results showed that extraordinary protective measures, the use of air treatment systems, and a continuous monitoring could be associated with decreased Aspergillus air contamination during construction, renovation, or demolition works.

Quality-of-life analysis of the MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG study comparing platinum-based versus non-platinum-based chemotherapy in patients with partially platinum-sensitive recurrent ovarian cancer.

Background: MITO-8 showed that prolonging platinum-free interval by introducing non-platinum-based chemotherapy (NPBC) does not improve prognosis of patients with partially platinum-sensitive recurrent ovarian cancer. Quality of life (QoL) was a secondary outcome. Patients and methods: Ovarian cancer patients recurring or progressing 6-12 months after previous platinum-based chemotherapy (PBC) were randomized to receive PBC or NPBC as first treatment. QoL was assessed at baseline, third and sixth cycles, with the EORTC C-30 and OV-28 questionnaires. Mean changes and best response were analysed. Progression-free survival, response rate, and toxicity are also reported for proper interpretation of data. All analyses were based on intention-to-treat. Results: Out of the 215 patients, 151 (70.2%) completed baseline questionnaire, balanced between the arms; thereafter, missing rate was higher in the NPBC arm. At mean change analysis, C30 scores were prevalently worse in the NPBC than PBC arm, statistical significance being attained for emotional functioning, global health status/QoL, fatigue, and dyspnoea (effect sizes ranging from 0.30 to 0.51). Conversely, as for OV28 scale, the other chemotherapy side-effects item was significantly worse with PBC at three and six cycles, with a larger effect size (0.70 and 0.54, respectively). At best response analysis, improvement of emotional functioning and pain and worsening of peripheral neuropathy and other chemotherapy side-effects were significantly more frequent in the PBC arm. Progression-free survival (median 9 versus 5 months, P = 0.001) and objective response rate (51.6% versus 19.4%, P = 0.0001) were significantly better with PBC. Allergy, blood cell count, alopecia, nausea, musculoskeletal, and neurological side-effects were more frequent and severe with PBC; hand-foot skin reaction, rash/desquamation, mucositis, and vascular events were more frequent with NPBC. Conclusion: MITO-8 QoL analysis shows that deterioration of some functioning and symptom scales is lower with PBC, with improvement of emotional functioning and pain, despite worsening of toxicity-related items. ClinicalTrials.gov: NCT00657878.

Transcriptional Analysis of serk1 and serk3 Coreceptor Mutants.

Somatic embryogenesis receptor kinases (SERKs) are ligand-binding coreceptors that are able to combine with different ligand-perceiving receptors such as BRASSINOSTEROID INSENSITIVE1 (BRI1) and FLAGELLIN-SENSITIVE2. Phenotypical analysis of serk single mutants is not straightforward because multiple pathways can be affected, while redundancy is observed for a single phenotype. For example, serk1serk3 double mutant roots are insensitive toward brassinosteroids but have a phenotype different from bri1 mutant roots. To decipher these effects, 4-d-old Arabidopsis (Arabidopsis thaliana) roots were studied using microarray analysis. A total of 698 genes, involved in multiple biological processes, were found to be differentially regulated in serk1-3serk3-2 double mutants. About half of these are related to brassinosteroid signaling. The remainder appear to be unlinked to brassinosteroids and related to primary and secondary metabolism. In addition, methionine-derived glucosinolate biosynthesis genes are up-regulated, which was verified by metabolite profiling. The results also show that the gene expression pattern in serk3-2 mutant roots is similar to that of the serk1-3serk3-2 double mutant roots. This confirms the existence of partial redundancy between SERK3 and SERK1 as well as the promoting or repressive activity of a single coreceptor in multiple simultaneously active pathways.

Work related stress and blood glucose levels.

AIM: The aim of the study is to evaluate work-related subjective stress in a group of workers on a major Italian company in the field of healthcare through the administration of a valid "questionnaire-tool indicator" (HSE Indicator Tool), and to analyze any correlation between stress levels taken from questionnaire scores and blood glucose values. MATERIAL AND METHODS: We studied a final sample consisting of 241 subjects with different tasks. The HSE questionnaire - made up of 35 items (divided into 7 organizational dimensions) with 5 possible answers - has been distributed to all the subjects in occasion of the health surveillance examinations provided by law. The questionnaire was then analyzed using its specific software to process the results related to the 7 dimensions. These results were compared using the Pearson correlation and multiple linear regression with the blood glucose values obtained from each subject. RESULTS: From the analysis of the data the following areas resulted critical, in other words linked to an intermediate (yellow area) or high (red area) condition of stress: sustain from managers, sustain from colleagues, quality of relationships and professional changes. A significant positive correlation (p <0.05) between the mean values of all critical areas and the concentrations of glucose values have been highlighted with the correlation index of Pearson. Multiple linear regression confirmed these findings, showing that the critical dimensions resulting from the questionnaire were the significant variables that can increase the levels of blood glucose. CONCLUSION: The preliminary results indicate that perceived work stress can be statistically associated with increased levels of blood glucose.

Work-related stress in healthcare workers.

BACKGROUND: In the assessment of work-related stress it is crucial to find the factors that generate and increase it in order to identify categories of individuals at risk, to plan interventions for prevention, elimination or reduction of risk. The aim of the study is to assess the subjective stress in 68 workers of a large Italian company dealing with human health, through the use of a questionnaire-indicating tool, elaborated by the Italian National Institute for insurance against accidents at work (INAIL) and developed by the Health and Safety Executive (HSE). METHODS: We studied a final sample of 68 individuals (34 drivers/rescuers and 34 video display unit (VDU) operators). The questionnaire consists of 35 items (divided into six areas) with five possible answers each, that cover working conditions considered potential causes of stress. RESULTS: The drivers/rescuers had a better performance than the VDU operators, especially in the areas "demand", "relationships" and "role". We compared men and women in the two groups, finding that, in VDU operators, women had a better performance than men in all areas, except "role" and "changes", in which the overall scores were the same in men and women. In the drivers/rescuers women showed more critical scores in the items "relationships" and "change". CONCLUSION: The results show that: the questionnaire-indicating tool is useful, with a demonstrated effectiveness for the occupational physician during the visits and proven validity; additional future efforts should focus on understanding the psycho-social, organizational and individual problems related to stress and the consequent implementation of preventive measures.

Brassinosteroids inhibit pathogen-associated molecular pattern-triggered immune signaling independent of the receptor kinase BAK1.

Plants and animals use innate immunity as a first defense against pathogens, a costly yet necessary tradeoff between growth and immunity. In Arabidopsis, the regulatory leucine-rich repeat receptor-like kinase (LRR-RLK) BAK1 combines with the LRR-RLKs FLS2 and EFR in pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and the LRR-RLK BRI1 in brassinosteroid (BR)-mediated growth. Therefore, a potential tradeoff between these pathways mediated by BAK1 is often postulated. Here, we show a unidirectional inhibition of FLS2-mediated immune signaling by BR perception. Unexpectedly, this effect occurred downstream or independently of complex formation with BAK1 and associated downstream phosphorylation. Thus, BAK1 is not rate-limiting in these pathways. BRs also inhibited signaling triggered by the BAK1-independent recognition of the fungal PAMP chitin. Our results suggest a general mechanism operative in plants in which BR-mediated growth directly antagonizes innate immune signaling.

Ballet and stress. A pilot study.

BACKGROUND: Work-related stress is a complex problem requiring a work environment-based assessment. Artists like dancers represent a category of atypical workers potentially at high risk for work-related stress. Aim of our pilot study is to evaluate organizational stress in a population of professional dancers, using the HSE Indicator Tool for Work Related Stress. METHODS: We administered the Italian version of the HSE Indicator Tool to 38 ballet dancers, males and females. The questionnaire evaluates 7 key organizational dimensions: demand, control, managers' support, peer support, relationships, role and change. RESULTS: The standards required-ideal conditions are achieved in none of the above-mentioned dimensions. Change is the only dimension for which results fall between the 20th and the 50th percentile, while for other dimensions results fall below the 20th percentile suggesting the need for immediate corrective action. In male dancers an acceptable situation is highlighted for the dimension "change" compared to female dancers. In both sexes there is a high frequency of subjects complaining of verbal abuse, bullying and harassment. CONCLUSIONS: Despite the small sample size, our pilot study highlights the presence of heightened levels of organizational stress. Preventive measures targeted towards improving communication between managers and dancers and aimed at team building should be implemented.

Analysis of plasma cytokines and angiogenic factors in patients with pretreated urothelial cancer receiving Pazopanib: the role of circulating interleukin-8 to enhance the prognostic accuracy.

BACKGROUND: Pazopanib achieved the end point of clinical activity in pretreated patients with urothelial cancer in a single-group, phase 2 trial. The objective was to identify biological predictors of clinical benefit to pazopanib in these patients. METHODS: EDTA blood samples were collected at baseline (T0) and after 4 weeks (T1) of treatment, together with radiological imaging in all 41 patients to analyse plasma circulating angiogenic factor levels by multiplex ELISA plates. Changes from T0 to T1 in marker levels were matched with response with the covariance analysis. Univariable and multivariable analyses evaluated the association with overall survival (OS), adjusted for prespecified clinical variables. Net reclassification improvement (NRI) tested the performance of the recognised Cox model. RESULTS: Increasing IL8(T1) level associated with lower response probability at covariance analysis (P=0.010). Both IL8(T0) (P=0.019) and IL8(T1) (P=0.004) associated with OS and the prognostic model, including clinical variables and IL8(T1) best-predicted OS after backward selection. The NRI for this model was 39%.When analysed as a time-varying covariate, IL8(T1) level<80 pg ml(-1) portended significantly greater response (∼80%) and 6-month OS (∼60%) probability than level ≥ 80. CONCLUSION: IL8-level changes during pazopanib allowed for a prognostic improvement and were associated with response probability.

Visualization of BRI1 and BAK1(SERK3) membrane receptor heterooligomers during brassinosteroid signaling.

The leucine-rich repeat receptor-like kinase BRASSINOSTEROID-INSENSITIVE1 (BRI1) is the main ligand-perceiving receptor for brassinosteroids (BRs) in Arabidopsis (Arabidopsis thaliana). Binding of BRs to the ectodomain of plasma membrane (PM)-located BRI1 receptors initiates an intracellular signal transduction cascade that influences various aspects of plant growth and development. Even though the major components of BR signaling have been revealed and the PM was identified as the main site of BRI1 signaling activity, the very first steps of signal transmission are still elusive. Recently, it was shown that the initiation of BR signal transduction requires the interaction of BRI1 with its SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE (SERK) coreceptors. In addition, the resolved structure of the BRI1 ectodomain suggested that BRI1-ASSOCIATED KINASE1 [BAK1](SERK3) may constitute a component of the ligand-perceiving receptor complex. Therefore, we investigated the spatial correlation between BRI1 and BAK1(SERK3) in the natural habitat of both leucine-rich repeat receptor-like kinases using comparative colocalization analysis and fluorescence lifetime imaging microscopy. We show that activation of BR signaling by exogenous ligand application resulted in both elevated colocalization between BRI1 and BAK1(SERK3) and an about 50% increase of receptor heterooligomerization in the PM of live Arabidopsis root epidermal cells. However, large populations of BRI1 and BAK1(SERK3) colocalized independently of BRs. Moreover, we could visualize that approximately 7% of the BRI1 PM pool constitutively heterooligomerizes with BAK1(SERK3) in live root cells. We propose that only small populations of PM-located BRI1 and BAK1(SERK3) receptors participate in active BR signaling and that the initiation of downstream signal transduction involves preassembled BRI1-BAK1(SERK3) heterooligomers.

Work related etiology of amyotrophic lateral sclerosis (ALS): a meta-analysis.

BACKGROUND: The aim of this meta-analysis was to evaluate the association between ALS and occupational exposure to physical (ELF-EMF) and chemicals (solvents, heavy metals and pesticides) agents. METHODS: We considered articles published from 1980 up to April 2013; in total, 750 publications were evaluated. The studies had to satisfy the following criteria: 1) cohort or case-control studies; 2) the presence of individual exposures; 3) clinical diagnosis of sporadic ALS or sporadic ALS on the death certificate. We followed the evaluation of quality in two steps. The first step classified studies according to a rating system based on a mix of criteria developed by scientific organizations, especially developed for studies of risk factors for ALS. The ratings obtained range from I (highest) to V (lowest). The data on risk factors derived from studies with Armon ratings of I, II, and III can reach levels of evidence A (established risk factor), B (likely risk factor), or C (possible risk factor). The second step evaluated the exposure and a score from 1 to 4 was assigned to each item; an exposure with a score of 3 or 4 was considered sufficient. Different analyses were performed on ALS and exposure to metals, solvents, pesticides and electromagnetic fields. In our study the heterogeneity was assessed both by χ2-based Q-tests and through the index of inconsistency I² while the measure RR/OR and CI of 95% to estimate the relationship between ALS and the various considered risk factors was employed. RESULTS: The association between exposure to pesticides and ALS as a whole is weak and not significant. With regard to the results of individual studies the following critical synthesis can be reported: 1) the selected studies showed a low level of association between ALS and electromagnetic fields; 2) as regards the solvents, the association with ALS in some studies is combined with a slightly increased risk, particularly in women, and in others a slight but significant linear association is observed; 3) for the metals, in some cases there was a stronger association in women than in men; for individual metals, there was an association especially with chromium and lead; 4) lastly, with regard to the products of agricultural pesticides in general, there was an association with ALS in men but not in women, with a dose-response relationship. CONCLUSIONS: The lack of statistically significant association between occupational exposure and ALS is mainly due to the methodological diversity of the studies and the lack of prospective studies at the workplace.

Urinary hydroxypyrene and estradiol in an occupationally exposed "outdoor" population.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are widely present in the air pollution. The urinary hydroxypyrene (1-HOPu) is considered the main biological biomarker currently available to measure the exposure to PAH. It is supposed responsible of an increase of estradiol levels in males. Aim of this study is to verify whether there is a relation between 1-HOPu and plasmatic estradiol in non-smoker male workers. METHODS: The study was conducted on a sample of 122 non-smoker policemen in a large Italian city; we monitored their levels of 1-HOPu and the values of estradiol. The sample was divided into three groups according to the levels of urinary hydroxypyrene. The indices of correlation (r) and multiple linear regression (ß), between levels of 1-HOPu and estradiol were calculated. It was also calculated the student's t-test among the groups to check the differences. RESULTS: We found statistically significant correlations and multivariate linear regressions between 1-HOPu and estradiol in the total sample and in group III (levels of 1-HOPu above the 75th percentile). The average levels of estradiol in group III was statistically and significantly higher than in the group I (levels of 1-HOPu below the 25th percentile) and group II (levels 1-HOPu between 25th and the 75th percentile). CONCLUSIONS: 1-HOPu in non-smoker male workers is related with an increase of plasmatic estradiol. We believe that PAHs, of which 1-HOPu is the main biomarker, can interact with the hypothalamic-pituitary axis. The preliminary results suggest that the topic needs further research on male and female as well.

Occupational exposure to urban stressors and effects on atrial natriuretic peptide: preliminary results.

PURPOSE: The aim of this pilot study is to evaluate whether occupational exposure to low doses of pollutants present in the air of the city selected for the study could cause alterations in the concentration of atrial natriuretic peptide (ANP) in workers from the Municipal Police with outdoor tasks, compared to those with indoor tasks. METHODS: A total of 208 non-smoking male and female subjects were enrolled and divided on the basis of whether their tasks were mainly outdoors or indoors. The dosage of plasma ANP was carried out on all workers included in the study. Differences between means and frequencies were compared using student's t-test for unpaired data and chi-square test with Yates' correction, and they were considered significant when the p value was <0.05. RESULTS: Even after the subdivision of the total sample on the basis of sex, mean plasma levels of ANP were higher but not statistically significant in traffic police compared with controls. CONCLUSIONS: The preliminary results suggest that further studies should be conducted before the influence of urban pollution on ANP could be confirmed or rejected.

Workers of the printing industry and hepatic damage.

BACKGROUND: Typesetting industry is still the primary instrument of communication, despite the development of new technological systems. This study focuses on the analysis of the hepatic effects induced by the use of some organic solvents employed in the printing industry. METHODS: We studied a group of 194 workers: 93 exposed and 101 not exposed. The level of the exposure to chemical pollutants were assessed through the environmental monitoring of blood concentrations and the analysis of airborne substances. The health survey was performed through the collection of the medical history and the use of hepatic tests, which were evaluated by calculating Mean, Standard Deviation, Student's t-test and X² test with Yates Correction, to investigate statistically significant differences in some hepatic parameters: AST, ALT, ALP, GGT, fractional and total bilirubin. The environmental data sometimes exceeded the TLV-TWA. RESULTS: The clinical evaluation of the hepatic parameters showed statistically significant differences as to the hematic concentrations of AST, ALT, GGT. CONCLUSIONS: The results we obtained support the hypothesis of a risk among the printing industrial workers attributable to the hepatotoxic solvents. This risk seems to be related to the use of a mixture of solvents, although at low doses, and the analysis of the results obtained confirms the validity of the investigation for the health screening protocol adopted in order to identify subjects and/or population at risk of hepatotoxicity.

Liver damage in automotive and industrial workers of the glass.

OBJECTIVE: High doses of organic solvents can cause hepatic disease. We investigated whether exposure to low doses of solvents in automotive and industrial workers may lead to changes in liver tests. METHODS: We studied the liver parameters (glutamic oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), gamma-glutamyl-traspeptidasi (γ-GT), alkaline phosphatase (PHA), total (TB) and direct bilirubin (DB) of 24 workers exposed to organic solvents and of 30 unexposed controls. RESULTS: A significant increase of GOT, GPT and γ-GT was found in exposed workers compared to unexposed controls workers. The ratio GPT/GOT was significantly higher among the exposed compared to controls. CONCLUSIONS: The results confirmed the hypothesis that exposure to low doses of solvents may determine a liver damage.

Safety and activity of sunitinib in elderly patients (≥ 70 years) with metastatic renal cell carcinoma: a multicenter study.

BACKGROUND: Actual tolerability of sunitinib is still poorly documented in elderly patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Charts of elderly patients treated with sunitinib for mRCC were reviewed in six Italian centers to assess safety (primary objective), efficacy and correlation of toxicity with comprehensive geriatric assessment (CGA) (secondary objectives). RESULTS: Sixty-eight patients were eligible, and the median age was 74 years. CGA was carried out in 34 patients (41% fit, 41% vulnerable and 18.5% frail). The dose reduction to 37.5 mg was made upfront or soon after the first cycle in 69.1%. More frequent toxic effects were fatigue (80.9%), mucositis (61.8%) and hypertension (58.8%). Cardiac events occurred in nine patients. In 10 patients, therapy was interrupted early due to rapidly progressive disease (10.3%) or severe toxicity (4.4%: 1 cardiac failure, 1 fatigue, 1 febrile neutropenia). At a median follow-up of 27.1 months, the median OS was 18.3 months and the median PFS was 13.6 months. Correlation was not found between frailty at CGA with severe toxicity nor with response. CONCLUSIONS: Treatment with sunitinib is effective in elderly patients; yet early interruptions were frequent. Starting treatment at reduced dose and escalating in the absence of severe toxicity could be suggested.