Carbonic anhydrases III and IX are new players in the crosstalk between adrenocortical carcinoma and its altered adipose microenvironment.

PURPOSE: Adrenocortical carcinoma (ACC), a rare malignancy of the adrenocortex, is characterized by a crosstalk between the adipose microenvironment and tumor. Here, we assessed the involvement of carbonic anhydrase (CA) enzymes III and IX (CAIII and CAIX), in the metabolic alterations of the adipose tissue characterizing obesity and in the local crosstalk between the tumor adipose microenvironment and ACC. RESULTS/METHODS: CAIII and CAIX expression is altered in visceral adipose tissue (VAT) in obesity and in ACC. A significant CAIX upregulation was present in ACC at advanced stages (n = 14) (fold increase FI = 7.4 ± 0.1, P < 0.05) associated with lower CAIII levels (FI = 0.25 ± 0.06, P < 0.001), compared with lower stages (n = 9). In vitro coculture between visceral adipose stem cells (ASCs) and ACC cell lines, H295R and MUC-1, mimicking the interaction occurring between VAT and advanced ACC, showed a significant CAIX upregulation in H295R but not in MUC-1 cells, and a decreased expression of CAIII. The effect on adipose cells was different when cocultured with H295R or MUC-1 cells. Coculture did not modulate CAIII expression in ASCs, which, however, was significantly downregulated with H295R (FI = 0.34 ± 0.11, P < 0.05) and upregulated by MUC-1 when cocultured ASCs were induced to differentiate toward adipocytes, with an expression profile similar to what found in VAT of obese subjects. CAIX expression was markedly increased in ASCs cocultured with H295R and to a less extent following adipogenesis induction (FI = 150.9 ± 46.5 and FI = 4.6 ± 1.1, P < 0.01, respectively). CONCLUSION: Our findings highlight a modulation of CAIII and CAIX in the metabolic crosstalk between ACC and its local adipose microenvironment, suggesting that CAs might represent a potential target for novel anticancer therapies.

Differences in clinicopathological features and distribution of risk factors in Italian melanoma patients.

BACKGROUND: No studies are available in the literature on the distribution of different melanoma features and risk factors in the Italian geographical areas. OBJECTIVE: To identify the differences in clinical-pathological features of melanoma, the distribution of risk factors and sun exposure in various Italian macro-areas. METHODS: Multicentric-observational study involving 1,472 melanoma cases (713 north, 345 centre, 414 south) from 26 referral centres belonging to the Italian Multidisciplinary Group for Melanoma. RESULTS: Melanoma patients in northern regions are younger, with thinner melanoma, multiple primaries, lower-intermediate phototype and higher counts of naevi with respect to southern patients; detection of a primary was mostly connected with a physician examination, while relatives were more involved in the south. Northern patients reported a more frequent use of sunbeds and occurrence of sunburns before melanoma despite sunscreen use and a lower sun exposure during the central hours of the day. CONCLUSIONS: The understanding of differences in risk factors distribution could represent the basis for tailored prevention programmes.

Familial and sporadic melanoma: different clinical and histopathological features in the Italian population - a multicentre epidemiological study - by GIPMe (Italian Multidisciplinary Group on Melanoma).

BACKGROUND: Having a familial member affected by cutaneous melanoma is a risk factor for this neoplasm. Only a few epidemiological case-control studies have been carried out to investigate whether familial and sporadic melanomas show different clinical and histopathological features. OBJECTIVE: The aim of this study was to evaluate eventual different features and risk factors in subjects affected by familial and sporadic cutaneous melanoma. METHODS: A case-control multicentre study interesting 1407 familial (n = 92) and sporadic (n = 1315) melanomas in the Italian population. The analysis was made using t-test for continuous variables and chi-squared test for categorized ones. The variables which have shown statistically significant differences in the two groups in the univariate analysis were included in a multivariate model. RESULTS: The results showed some main significantly clinical differences between the two groups investigated: earlier age at diagnosis, a greater proportion of sunburns and a higher number of naevi were observed for the familial cases compared with sporadic ones. Nevertheless, we did not find a diagnostic anticipation in familial melanomas, in fact the invasion level and the thickness of melanomas was similar in the two groups. CONCLUSION: Some relevant clinical differences are observed between the two groups examined. The familial melanoma members, although carriers of constitutional risk factors, are not careful enough to primary and secondary prevention.

A Testing Environment for Continuous Colormaps.

Many computer science disciplines (e.g., combinatorial optimization, natural language processing, and information retrieval) use standard or established test suites for evaluating algorithms. In visualization, similar approaches have been adopted in some areas (e.g., volume visualization), while user testimonies and empirical studies have been the dominant means of evaluation in most other areas, such as designing colormaps. In this paper, we propose to establish a test suite for evaluating the design of colormaps. With such a suite, the users can observe the effects when different continuous colormaps are applied to planar scalar fields that may exhibit various characteristic features, such as jumps, local extrema, ridge or valley lines, different distributions of scalar values, different gradients, different signal frequencies, different levels of noise, and so on. The suite also includes an expansible collection of real-world data sets including the most popular data for colormap testing in the visualization literature. The test suite has been integrated into a web-based application for creating continuous colormaps (https://ccctool.com/), facilitating close inter-operation between design and evaluation processes. This new facility complements traditional evaluation methods such as user testimonies and empirical studies.

Isolation and characterisation of colistin-resistant Enterobacterales from chickens in Southeast Nigeria.

OBJECTIVES: Resistance to colistin (CST) mediated by mobile genetic elements has had a broad impact worldwide. There is an intensified call for epidemiological surveillance of mcr in different reservoirs to preserve CST for future generations. In Nigeria, the poultry industry is a key livestock sector. This study was undertaken to screen putative colistin-resistant Enterobacterales (CST-r-E) from poultry birds in Southeast Nigeria and to determine the genetic relatedness of mcr-harbouring isolates. METHODS: Faecal and cloacal swab samples (n = 785) were collected from chickens in 17 farms located in three contiguous states in Southeast Nigeria between March-November 2018. Following selective culture, CST-r-E were isolated. Confirmation of CST resistance, antimicrobial susceptibility testing, molecular detection of genes mcr-1 to mcr-10, multilocus sequence typing (MLST) and randomly amplified polymorphic DNA (RAPD) analysis were performed on the isolates. A questionnaire was distributed to investigate the knowledge about CST and its use of chicken farm caretakers. RESULTS: Of the 785 samples evaluated, 45 (5.7%) were positive for 48 CST-r-E, among which 23 harboured the mcr-1 gene (22 Escherichia coli and 1 Klebsiella pneumoniae). In two E.coli isolates, a new allelic variant (mcr-1.22) was detected. RAPD analysis allowed the identification of 11 different fingerprints. MLST also revealed 11 STs, with 3 of them being novel. CONCLUSION: mcr has significantly spread in poultry birds of Southeast Nigeria, which poses a worrisome risk to veterinary and human health. Strategies to prevent indiscriminate use of CST in farms should be quickly adopted before CST resistance becomes a huge global health issue.

How staging of thin melanoma is changed after the introduction of TNM 7th edition: a population-based analysis.

INTRODUCTION: In 2009, the American Joint Committee on Cancer (AJCC) incorporated the tumor mitotic rate in the melanoma pathological TNM staging system. To investigate the effect of this change on the pT1 substaging of primary cutaneous melanomas, we reclassified the cases collected by a cancer registry according to the 6th and the 7th editions of AJCC melanoma staging. METHODS: Patients with pathological T1 melanoma diagnosed in the period 2000-2008 were selected from Tuscan Cancer Registry. The histological reports were reviewed and pT1 melanomas classified according to both the 6th and the 7th editions of the AJCC staging system. The shift of melanomas between pT1 substages was analyzed. RESULTS: Among the 242 pT1 melanomas collected in the study period and with mitotic index available, there were 202 (83 % of all pT1) and 175 (72 %) pT1a, according to the 6th and the 7th editions of the AJCC melanoma staging, respectively. When the 7th edition was used, 20 % of all pT1a melanomas shifted to pT1b, and 32 % of all pT1b melanomas shifted to pT1a. A poor level agreement between the two TNM staging systems, measured by the Cohen's kappa coefficient, was found (K = 0.37). CONCLUSIONS: The addition of mitotic activity to the pathological staging resulted in an increase in pT1b proportion and in a change in the classification of some cases. This modification could influence the clinical approach, with a different use of the sentinel lymph node biopsy, and underlines the role of mitosis evaluation in the management of thin melanoma patients.

Ease-of-use protocol for the rapid detection of third-generation cephalosporin resistance in Enterobacteriaceae isolated from blood cultures using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry.

An ease-of-use protocol for the identification of resistance against third-generation cephalosporins in Enterobacteriaceae isolated from blood culture bottles was evaluated using matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. A cefotaxime hydrolysis assay from chocolate agar subcultures using antibiotic discs and without inoculum standardization was developed for routine work flow, with minimal hands-on time. This assay showed good performance in distinguishing between cefotaxime-susceptible and cefotaxime-resistant strains, with excellent results for Escherichia coli (sensitivity 94.7%, specificity 100%). However, cefotaxime resistance was not detected reliably in Enterobacteriaceae expressing AmpC genes or carbapenemase-producing Klebsiella pneumoniae.

Rabeprazole is equivalent to omeprazole in the treatment of erosive gastro-oesophageal reflux disease. A randomised, double-blind, comparative study of rabeprazole and omeprazole 20 mg in acute treatment of reflux oesophagitis, followed by a maintenance open-label, low-dose therapy with rabeprazole.

BACKGROUND: Previous studies have shown similar effects of rabeprazole and omeprazole, when used at the same dose in the treatment of reflux oesophagitis. However, such studies have been conducted as superiority studies but interpreted as equivalence ones. AIM: To properly assess the comparative efficacy of rabeprazole and omeprazole in inducing complete endoscopic healing and symptom relief in patients with reflux oesophagitis. METHODS: Patients (n=560) with Savary-Miller grade I-III reflux oesophagitis were randomised in a double-blind, double-dummy fashion to rabeprazole or omeprazole 20 mg once daily for 4-8 weeks. Then, patients endoscopically healed and symptomatically relieved were openly maintained with rabeprazole 10 mg or 2x10 mg once daily (in the event of clinical and/or endoscopic relapse) for a maximum of 48 weeks. RESULTS: After 4-8 weeks of treatment, healing (primary end-point) was observed in 228/233 (97.9%) patients in the rabeprazole group and in 231/237 (97.5%) in the omeprazole one (equivalence effect demonstrated by p<0.0001 at Blackwelder test and an upper confidence limit at 97.5% of 0.023). However, rabeprazole was faster in inducing heartburn relief than omeprazole (2.8+/-0.2 versus 4.7+/-0.5 days of therapy to reach the first day with satisfactory heartburn relief, p=0.0045 at log-rank test). In the maintenance phase, 15.2% of patients had an endoscopic and/or clinical relapse. CONCLUSION: Rabeprazole is equivalent to omeprazole in healing reflux oesophagitis, but shows a faster activity on reflux symptoms in the early treatment phase.

Characterization of a fourth lipoprotein from Pasteurella haemolytica A1 and its homology to the OmpA family of outer membrane proteins.

A fourth lipoprotein gene from Pasteurella haemolytica A1 was cloned and characterized. The plpD gene encodes a 31-kDa lipoprotein (Plp4) which could be recognized in Western immunoblot by sera from calves immunized with the culture supernatant vaccine Presponse. This suggests that Plp4 is one of the immunogenic molecules in the P. haemolytica A1 culture supernatant. The lipoprotein nature of Plp4 was confirmed by labelling with [3H]palmitate and inhibition of leader peptide cleavage with globomycin. A homology search with databanks showed extensive homology between Plp4 and a 31-kDa antigen from Haemophilus somnus and a 19.2-kDa antigen from Neisseria meningitidis. Additional homology of the distal half of Plp4 was identified with a number of bacterial outer membrane proteins belonging to the OmpA family. Plp4 appears to be a novel type of outer membrane protein that contains motifs typical of OmpA but which is also lipid modified.

Epidemiology of atypical melanocytic naevi: an analytical study in a Mediterranean population.

Atypical naevi are markers for increased risk of malignant melanoma, providing additional information about melanoma risk beyond that given by common melanocytic naevi. Little is known about the epidemiology of atypical naevi (AN), and available data are limited to predominantly fair-skinned populations. By using a case-control study that included 705 subjects with atypical naevi and 1,782 controls, we have analysed the aetiology of AN in a Mediterranean population, paying particular attention to the role of sunburn. After adjusting for age, sex and years of formal education, the presence of atypical naevi was significantly related to frequent sunburn before the age of 20 (odds ratio, OR, = 1.8; 95% CI, 1.3-2.5). Although less evident, this relationship was maintained by also taking into account the sun sensitivity, expressed as phototype, as a cofounder (OR = 1.5; 95% CI, 1.0-2.0). Concerning phenotypical features, an increased risk of having atypical naevi was found for all the parameters included in so-called 'fair complexion', i.e. blue eyes, blond or red hair, fair skin, phototype I-II, and a tendency to freckle. The greatest difference between subjects with and without atypical naevi related to the number of common melanocytic naevi: more than 30 common naevi were found in 41.5% of cases, but only in 9% of controls (OR = 8.0; 95% CI, 6.3-10.3). Overall, the six variables entered in the multivariate model that best predicted the risk of atypical naevi, were: young age, male sex, high educational level, presence of a large number of common naevi, phototype I-II, and a history of painful sunburn. In conclusion, the variables predicting the risk of developing atypical naevi in Mediterranean people are identical to those observed in predominantly fair-skinned populations. The aetiologic role of sunlight has been pointed out and shows a statistically significant relationship between frequent sunburn and the development of atypical naevi also after controlling for the subject's phototype.

[Study of somatosensory evoked potentials in full-term and premature neonates]. / Studio dei potenziali evocati somestesici in neonati a termine e pretermine.

The electrophysiological maturation of both peripheral and 'central' (spinal + superspinal) nervous fibers belonging to peroneal and medial nerves was evaluated within the 1st month of extrauterine life. Thirty-five newborns with different gestational ages (15 FT, 20 PT), have been examined through the SEP technique during percutaneous stimulation of median (wrist and index finger) and peroneal (popliteal fossa) nerves. Recording electrodes were placed at Erb's point, lumbar and cervical spine, scalp sites corresponding to the sensory areas for upper and lower limb. Peripheral conduction velocities were correlated with chronological ages but they did not correlate neither with gestational ages nor with birth weightes. Central conduction velocities correlated with gestational ages. The role of maturation was faster for the former than for the latter.

[Long-term effects of neonatal medium-degree hyperbilirubinemia on brainstem evoked potentials]. / Effetti a lungo termine della iperbilirubinemia neonatale di modico grado sui potenziali evocati troncoencefalici.

Since neonatal hyperbilirubinemia (greater than 20 mg/100 ml) represents a risk factor for acoustic defects, we examined the effects of moderate hyperbilirubinemia less than 20 mg/100 ml) on the acoustic pathway maturation through the BAEPs technique. Twenty-three children who had suffered from moderate neonatal hyperbilirubinemia (5 FT, 18 PT) were tested at the end of their 1st year. No statistically significant differences were found between their response characteristics and those of a similarly aged control group. We conclude that a low-to-moderate degree of hyperbilirubinemia at birth should not be considered as a potential risk factor affecting the auditory brainstem pathways maturation and functionality.

Predictors of skin self-examination in subjects attending a pigmented lesion clinic in Italy.

BACKGROUND: Skin self-examination (SSE) is associated with thinner melanomas in both North American and Italian patients. The knowledge of conditions associated with SSE may help in refining educational strategies for the prevention of melanoma. OBJECTIVE: The aim of the study was to investigate the frequency of SSE and the factors associated with SSE in subjects followed at a specialized pigmented lesion clinic (PLC) in Italy. PATIENTS/METHODS: A series of 299 consecutive subjects who visited the Florence PLC was investigated by means of a self-administered questionnaire regarding SSE habits. The statistical association between SSE and selected variables was examined by univariate and multivariate analyses. RESULTS: In the univariate analysis, variables significantly associated with SSE were: green/blue eyes, phototype I/II, the presence of large numbers of common acquired and atypical melanocytic naevi, sunscreen use, having had a previous PLC examination, and having received a leaflet explaining SSE. SSE was less frequent in women using sunbeds and more frequent in those performing breast self-examination. Using the multivariate model, which included all the variables associated with SSE in the previous analysis, we found that, among males, the only variable significantly associated with SSE was the report of having received a leaflet explaining SSE [odds ratio (OR) 3.02, 95% confidence interval (CI) 1.24-7.38]. Among females, having had a previous consultation at a PLC was significantly associated with SSE (OR 4.84, 95%CI 1.57-14.93); this might be because of the explanation and advice about skin cancer prevention customarily provided as a part of the PLC consultation at our department. CONCLUSION: Educational tools, including a leaflet explaining SSE and counselling given within previous PLC visits, seem to play a crucial role in promoting SSE habits in subjects followed at a specialized PLC consultation.

[Artificial nutrition in oncologic surgery: our experience]. / Nutrizione artificiale in chirurgia oncologica nostra esperienza.

The authors present their experience about the use of artificial nutrition (AN) in oncologic surgical patients. They conclude that AN, in particular enteral nutrition, should be initiated early in the post-operative period, whenever possible, to achieve better results.

Simultaneous occurrence of multiple melanoma in situ on sun-damaged skin (lentigo maligna), solar lentigo and labial melanosis: the value of dermoscopy in diagnosis.

We report on a patient developing simultaneous occurrence of lentigo maligna lesions, solar lentigines and an extensive melanosis of the oral mucosa. Diagnostically, epiluminescence microscopy had a relevant role in the preoperative assessment and selection of suspicious pigmented lesions, as the lesions histologically labelled as lentigo maligna and solar lentigo were clinically indistinguishable. We review the clinical, dermoscopic and histopathologic differential diagnosis of solar lentigo, malignant lentigo and mucosal melanosis with other melanocytic and keratinocytic lesions and discuss the possible relationship between these entities.

Melanoma detection rate and concordance between self-skin examination and clinical evaluation in patients attending a pigmented lesion clinic in Italy.

BACKGROUND: The early diagnosis of melanoma is based on the collaboration between dermatologists and family doctors, who filter subjects to be referred to a pigmented lesion clinic (PLC). Following growing media coverage, there is increasing concern in the general population about the risk of the 'changing mole', resulting in a progressively increased workload in PLCs. AIM AND METHODS: We investigated the causes of referral to a PLC in a series of 193 attendees seen consecutively at the PLC of the University of Florence. Because the number of naevi is the major risk factor for melanoma in Mediterranean populations, the concordance between self-counting of naevi and the clinical evaluation of a PLC dermatologist in order to classify high-risk individuals was also investigated. RESULTS: Detection of a clinically suspicious lesion at dermatological examination occurred in 13 of 193 subjects referred by general practitioners (6.7%), with three melanomas confirmed histologically (overall detection rate: three of 193, 1.6%). The positive predictive value of the 'presence of a suspicious lesion', the cause of referral in 39.9% of subjects, was 9.1% when based on the gold standard criterion represented by the clinical detection of a suspicious lesion by the dermatologist and 3.8% based on the histological diagnosis of melanoma; the negative predictive value was 94.8% (100% when based on the histological diagnosis of melanoma), suggesting that the clinical detection of a suspicious lesion in subjects with different causes of referral (such as risk factors for melanoma, or the need to be reassured about moles) is unlikely. There was poor agreement between self-evaluation based on the presence of multiple naevi and the dermatological examination (gold standard) for both common and atypical naevi. The highest concordance (kappa = 0.32, 95% confidence interval 0.20-0.43) was associated with a dichotomized count of naevi as up to 50 or more than 50 naevi. CONCLUSIONS: In order to reduce the PLC workload, the filtering role of the family doctor needs to be improved, so that only subjects with a specific suspicious lesion are referred to the PLC. The self-assessment of melanoma risk based on the presence of multiple naevi was not reliable.

Sun exposure and large numbers of common and atypical melanocytic naevi: an analytical study in a southern European population.

The study analysed the relationship between high counts of common naevi and numbers of atypical naevi (AN) in sites differing in exposure to the sun. A series of 90 subjects with 100 or more common naevi (cases) and 92 controls was investigated by means of a case-control study. A striking association between high numbers of common naevi and prevalence of AN (whole body) was found. The adjustment for phenotype and phototype did not obscure this association. Similar findings were obtained after exclusion of subjects with familiarity for melanoma. Cases had more AN than controls in all the body sites, except for the buttocks, where sun exposure can be considered minimal or absent: in this site, an excess of common naevi but not of AN was found. The present study suggests that subjects with high common naevi counts show a higher prevalence of AN independently of their complexion, sunburn history and family history of melanoma. Phenotypic expression of AN seems to be enhanced by direct sun exposure.

Antisperm antibodies in young boys.

The authors report the results of antisperm antibody tests carried out on a group of 159 pre-pubertal boys suffering from various testicular pathologies. The data show that 21% of the patients' sera showed antibody activity against antigens on the sperm of healthy fertile donors. None of the control sera was ASA positive. Some differences were observed in pathology and age distribution of positivity.

Clinical efficacy and endocrine activity of vorozole in postmenopausal breast cancer patients. Results of a multicentric phase II study.

BACKGROUND: Aminoglutethimide was the first aromatase inhibitor to be used successfully in breast cancer patients. However, this drug also inhibits mineralcorticoid and glucocorticoid synthesis, making co-medication with corticosteroids necessary, and it is often poorly tolerated. The primary objective of this trial was to evaluate the clinical efficacy and tolerability of vorozole, a new non-steroidal oral aromatase inhibitor, in postmenopausal breast cancer patients. The secondary objective was to evaluate the pharmacodynamic activity of the drug. SUBJECTS AND METHODS: Thirty-four postmenopausal patients previously treated with tamoxifen in the adjuvant setting and/ or for advanced disease were treated with vorozole, 2.5 mg once daily. Patients were monitored with respect to treatment efficacy and safety. Hormonal evaluations were performed at baseline and during the course of treatment in order to evaluate the pharmacodynamic efficacy and safety of vorozole. RESULTS: According to UICC criteria, there were seven responders, one complete and six partial, for an overall response rate of 21% (95% confidence interval (CI) 9%-38%). The median duration of response was 9.6 months (95% CI 4.6-0), the median time to progression for the entire group was 4.7 months (95% CI 2.9-6.6) and the median survival time was 29.7 months (95% CI 19.1-0). Tolerability was excellent to good in 97% of the patients. Oestradiol and oestrone levels were suppressed to the limit of detection of the assays used. No effect was observed on the other endocrine parameters. CONCLUSIONS: Our results suggest that vorozole is an effective and safe drug for the treatment of advanced postmenopausal breast cancer following tamoxifen failure.