Sarcopenic obesity and reduced BMD in young men living with HIV: body composition and sex steroids interplay.

PURPOSE: Sex steroids play a key role on male bone homeostasis and body composition (BC), their role in men living with HIV (MLWH) is less recognized. This study aimed at investigating the prevalence of low BMD, sarcopenia, and sarcopenic obesity (SO) and their relationship with sex steroids in MLWH aged < 50. METHODS: Prospective, cross-sectional, observational study on MLWH younger than 50 (median age 47.0 years). BC and BMD were evaluated with DXA. Two different definitions of sarcopenia were applied: appendicular lean mass/height2 (ALMI) < 7.26 kg/m2 or appendicular lean mass/body weight (ALM/W) < 28.27%. Low BMD was defined for Z-score < -2.0. Sarcopenia coupled with obesity identified SO. Serum total testosterone (T) and estradiol (E2) were measured by LC-MS/MS; free testosterone (cFT) was calculated by Vermeulen equation. RESULTS: Sarcopenia was detected in 107 (34.9%) and 44 (14.3%) out of 307 MLWH according to ALMI and ALM/W, respectively. The prevalence of SO was similar by using both ALMI (11.4%) and ALM/W (12.4%). Sarcopenic and SO MLWH had lower total T and cFT in both the definition for sarcopenia. BMD was reduced in 43/307 (14.0%). Serum E2 < 18 pg/mL was an independent contributing factor for sarcopenia, SO, and low BMD. CONCLUSIONS: T and E2 are important determinants of BC even in MLWH. This is among the first studies investigating the distribution of obesity phenotypes and the prevalence of SO among MLWH showing that SO is present in 11-12% of enrolled MLWH regardless of the definition used. However, deep differences emerged using two different diagnostic definitions.

New insights into the comorbid conditions of Turner syndrome: results from a long-term monocentric cohort study.

PURPOSE: Many questions concerning Turner syndrome (TS) remain unresolved, such as the long-term complications and, therefore, the optimal care setting for adults. The primary aim of this long-term cohort study was to estimate the incidence of comorbid conditions along the life course. METHODS: A total of 160 Italian patients with TS diagnosed from 1967 to 2010 were regularly and structurally monitored from the diagnosis to December 2019 at the University Hospital of Bologna using a structured multidisciplinary monitoring protocol. RESULTS: The study cohort was followed up for a median of 27 years (IQR 12-42). Autoimmune diseases were the comorbid condition with the highest incidence (61.2%), followed by osteoporosis and hypertension (23.8%), type 2 diabetes (16.2%) and tumours (15.1%). Median age of onset ranged from 22 years for autoimmune diseases to 39 years for type 2 diabetes. Malignant tumours were the most prominent type of neoplasm, with a cumulative incidence of 11.9%. Papillary thyroid carcinoma was the most common form of cancer, followed by skin cancer and cancer of the central nervous system. Only one major cardiovascular event (acute aortic dissection) was observed during follow-up. No cases of ischaemic heart disease, heart failure, stroke or death were recorded. CONCLUSIONS: This cohort study confirms the need for continuous, structured and multidisciplinary lifelong monitoring of TS, thus ensuring the early diagnosis of important comorbid conditions, including cancer, and their appropriate and timely treatment. In addition, these data highlight the need for the increased surveillance of specific types of cancer in TS, including thyroid carcinoma.

Steroid biomarkers for identifying non-classic adrenal hyperplasia due to 21-hydroxylase deficiency in a population of PCOS with suspicious levels of 17OH-progesterone.

OBJECTIVE: We aimed at defining the most effective routine immunoassay- or liquid chromatography-tandem mass spectrometry (LC-MS/MS)-determined steroid biomarkers for identifying non-classic adrenal hyperplasia due to 21-hydroxylase deficiency (21-NCAH) in a PCOS-like population before genotyping. METHODS: Seventy PCOS-like patients in reproductive age with immunoassay-determined follicular 17OH-progesterone (17OHP) ≥ 2.00 ng/mL underwent CYP21A2 gene analysis and 1-24ACTH test. Serum steroids were measured by immunoassays at baseline and 60 min after ACTH stimulation; basal steroid profile was measured by LC-MS/MS. RESULTS: Genotyping revealed 23 21-NCAH, 15 single allele heterozygous CYP21A2 mutations (21-HTZ) and 32 PCOS patients displaying similar clinical and metabolic features. Immunoassays revealed higher baseline 17OHP and testosterone, and after ACTH stimulation, higher 17OHP (17OHP60) and lower cortisol, whereas LC-MS/MS revealed higher 17OHP (17OHPLC-MS/MS), progesterone and 21-deoxycortisol and lower corticosterone in 21-NCAH compared with both 21-HTZ and PCOS patients. Steroid thresholds best discriminating 21-NCAH from 21-HTZ and PCOS were estimated, and their diagnostic accuracy in identifying 21-NCAH from PCOS was established by ROC analysis. The highest accuracy was observed for 21-deoxycortisol ≥ 0.087 ng/mL, showing 100% sensitivity, while the combination of 17OHPLC-MS/MS ≥ 1.79 ng/mL and corticosterone ≤ 8.76 ng/mL, as well as the combination of ACTH-stimulated 17OHP ≥ 6.77 ng/mL and cortisol ≤ 240 ng/mL by immunoassay, showed 100% specificity. CONCLUSIONS: LC-MS/MS measurement of basal follicular 21-deoxycortisol, 17OHP and corticosterone seems the most convenient method for diagnosing 21-NCAH in a population of PCOS with a positive first level screening, providing high accuracy and reducing the need for ACTH stimulation test.

Unilateral temporary diaphragmatic paralysis secondary to bronchial artery embolization in a girl with cystic fibrosis and massive hemoptysis: a case report.

BACKGROUND: Massive hemoptysis is a serious complication in Cystic Fibrosis (CF), occurring commonly in older patients. Bronchial artery embolization (BAE) can be performed to stop the bleeding. BAE is generally safe and effective, but can sometimes lead to serious complications. We report the first case of temporary unilateral diaphragmatic paralysis associated to lung consolidation following BAE in a pediatric CF female patient. This complication worsened the lung function of the patient who underwent lung transplantation after 9 months. CASE PRESENTATION: A 14 years old female CF patient followed by the CF center of Florence presented low-grade fever, cough increase and recurrent episodes of major hemorrhages such as to carry out a BAE. Within 24 h the patient started to complain of severe thoracic pain in the right hemithorax, increased dyspnea and fever. A computed tomographic angiography and a dynamic fluoroscopic evaluation revealed the right diaphragmatic paralysis, not present before the procedure. After 4 days the clinical condition and radiological imaging had improved with restored mobility of the right hemidiaphragm. Nine months later, she required mechanical ventilation, and subsequently the initiation of extracorporeal membrane oxygenation (ECMO) for a pulmonary exacerbation with septic shock. Lung transplantation in ECMO was performed with success. CONCLUSION: Clinicians should be aware of the possibility of phrenic nerve injury with BAE in pediatric CF patients.

Behavioral, socio-environmental, educational and demographic correlates of excess body weight in Italian adolescents and young adults.

BACKGROUND AND AIMS: Excess body weight (EBW) is the most prevalent nutritional disorder among adolescents worldwide. Identifying determinants of EBW may help find new intervention strategies. Behavioral, socio-economic, educational and demographic correlates of EBW were examined in a population of Italian adolescents, separately for males and females. METHODS AND RESULTS: As many as 1039 male and 2052 female students (aged 16-19 ys) attending the last three years of different types of high-school of the Emilia-Romagna region in Italy were offered participation, with 552 males and 841 females being finally evaluated. The prevalence of EBW was 21.0% in males and 14.1% in females. Step-wise multivariate logistic regression analyses were performed showing that EBW was negatively related to energy intake in males (odds ratio for 100 kcal/day (OR) = 0.94, 95% confidence interval (CI): 0.89 to 0.98; P = 0.008), and to father's educational attainment (OR = 0.70, 95% CI: 0.52 to 0.95; P = 0.020), but positively related to parental obesity (OR = 2.80, 95% CI: 1.65 to 4.76; P < 0.001). In females, EBW was positively related to parental obesity (OR = 1.94, 95% CI: 1.15 to 3.29; P = 0.013), but negatively to mother's educational attainment (OR = 0.66, 95% CI: 0.45 to 0.97; P = 0.034) and type of attended school (OR = 0.66, 95% CI: 0.49 to 0.89; P = 0.007). Mother's occupation was also an independent determinant of EBW status in females (OR = 0.39, 95% CI: 0.18 to 0.85; P = 0.018 for being unemployed vs blue-collar). CONCLUSION: Parental obesity is associated with EBW in male and female adolescents. Importantly, we found sex differences in socio-economic and educational factors impacting on EBW, supporting possible distinct area of investigation.

The steroid response to human chorionic gonadotropin (hCG) stimulation in men with Klinefelter syndrome does not change using immunoassay or mass spectrometry.

PURPOSE: Liquid-chromatography tandem mass-spectrometry (LC-MS/MS) was developed in parallel to Immunoassays (IAs) and today is proposed as the "gold standard" for steroid assays. Leydig cells of men with Klinefelter syndrome (KS) are able to respond to human chorionic gonadotropin (hCG) stimulation, even if testosterone (T) production was impaired. The aim was to evaluate how results obtained by IAs and LC-MS/MS can differently impact on the outcome of a clinical research on gonadal steroidogenesis after hCG stimulation. METHODS: A longitudinal, prospective, case-control clinical trial. (clinicaltrial.gov NCT02788136) was carried out, enrolling KS men and healthy age-matched controls, stimulated by hCG administration. Serum steroids were evaluated at baseline and for 5 days after intramuscular injection of 5000 IU hCG using both IAs and LC-MS/MS. RESULTS: 13 KS patients (36 ± 9 years) not receiving T replacement therapy and 14 controls (32 ± 8 years) were enrolled. T, progesterone, cortisol, 17-hydroxy-progesterone (17OHP) and androstenedione, were significantly higher using IAs than LC-MS/MS. IAs and LC-MS/MS showed direct correlation for all five steroids, although the constant overestimation detected by IAs. Either methodology found the same 17OHP and T increasing profile after hCG stimulation, with equal areas under the curves (AUCs). CONCLUSIONS: Although a linearity between IA and LC-MS/MS is demonstrated, LC-MS/MS is more sensitive and accurate, whereas IA shows a constant overestimation of sex steroid levels. This result suggests the need of reference intervals built on the specific assay. This fundamental difference between these two methodologies opens a deep reconsideration of what is needed to improve the accuracy of steroid hormone assays.

Perspectives of health care professionals on cancer cachexia: results from three global surveys.

BACKGROUND: Cachexia has a high prevalence in cancer patients and negatively impacts prognosis, quality of life (QOL), and tolerance/response to treatments. This study reports the results of three surveys designed to gain insights into cancer cachexia (CC) awareness, understanding, and treatment practices among health care professionals (HCPs). METHODS: Surveys were conducted globally among HCPs involved in CC management. Topics evaluated included definitions and synonyms of CC, diagnosis and treatment practices, and goals and desired improvements of CC treatment. RESULTS: In total, 742 HCPs from 14 different countries participated in the surveys. The majority (97%) of participants were medical oncologists or hematologists. CC was most frequently defined as weight loss (86%) and loss of appetite (46%). The terms loss of weight and decreased appetite (51% and 34%, respectively) were often provided as synonyms of CC. Almost half (46%) of the participants reported diagnosing CC and beginning treatment if a patient experienced a weight loss of 10%. However, 48% of the participants would wait until weight loss was ≥15% to diagnose CC and start treatment. HCPs also reported that 61%-77% of cancer patients do not receive any prescription medication for CC before Stage IV of disease is reached. Ability to promote weight gain was rated as the most important factor for selecting CC treatment. Key goals of treatment included ensuring that patients can cope with the cancer and treatment and have a QOL benefit. HCPs expressed desire for treatments with a more CC-specific mode of action and therapies that enhance QOL. CONCLUSIONS: These surveys underscore the need for increased awareness among HCPs of CC and its management.

The corticotrophin-releasing factor/urocortin system regulates white fat browning in mice through paracrine mechanisms.

OBJECTIVES: The corticotrophin-releasing factor (CRF)/urocortin system is expressed in the adipose tissue of mammals, but its functional role in this tissue remains unknown. METHODS: Pharmacological manipulation of the activity of CRF receptors, CRF1 and CRF2, was performed in 3T3L1 white pre-adipocytes and T37i brown pre-adipocytes during in vitro differentiation. The expression of genes of the CRF/urocortin system and of markers of white and brown adipocytes was evaluated along with mitochondrial biogenesis and cellular oxygen consumption. Metabolic evaluation of corticosterone-deficient or supplemented Crhr1-null (Crhr1(-/-)) mice and their wild-type controls was performed along with gene expression analysis carried out in white (WAT) and brown (BAT) adipose tissues. RESULTS: Peptides of the CRF/urocortin system and their cognate receptors were expressed in both pre-adipocyte cell lines. In vitro pharmacological studies showed an inhibition of the expression of the CRF2 pathway by the constitutive activity of the CRF1 pathway. Pharmacological activation of CRF2 and, to a lesser extent, inhibition of CRF1 signaling induced molecular and functional changes indicating transdifferentiation of white pre-adipocytes and differentiation of brown pre-adipocytes. Crhr1(-/-) mice showed increased expression of CRF2 and its agonist Urocortin 2 in adipocytes that was associated to brown conversion of WAT and activation of BAT. Crhr1(-/-) mice were resistant to diet-induced obesity and glucose intolerance. Restoring physiological circulating corticosterone levels abrogated molecular changes in adipocytes and the favorable phenotype of Crhr1(-/-) mice. CONCLUSIONS: Our findings suggest the importance of the CRF2 pathway in the control of adipocyte plasticity. Increased CRF2 activity in adipocytes induces browning of WAT, differentiation of BAT and is associated with a favorable metabolic phenotype in mice lacking CRF1. Circulating corticosterone represses CRF2 activity in adipocytes and may thus regulate adipocyte physiology through the modulation of the local CRF/urocortin system. Targeting CRF receptor signaling specifically in the adipose tissue may represent a novel approach to tackle obesity.

Transcriptional regulation of enniatins production by Fusarium avenaceum.

AIMS: The aim of this study was to analyse the transcriptional regulation of enniatins (ENs) production in Fusarium avenaceum. METHODS AND RESULTS: We develop a new method to quantify ENs in FDM agar medium. We performed an LC/MS/MS analysis to evaluate enniatin A, A1, B, B1 and B4 production by seven F. avenaceum strains and, in a time-course experiment, by ITEM 3404 to analyse the transcriptional regulation of the esyn1 gene. The expression profile, achieved by Real time reverse transcriptase assay, showed an activation of gene transcription at the seventh day of incubation, corresponding to the higher increase of total ENs production. Enniatin B was the most abundant ENs analogues, representing the 90% of total ENs. The relative percentage of ENs remained unaltered during the experiment. CONCLUSIONS: We reported a transcriptional regulation of esyn1 responsible for the modulation of ENs biosynthesis. SIGNIFICANCE AND IMPACT OF THE STUDY: Enniatins are cyclic depsipeptides metabolites with a wide range of biological activities. They are also widespread contaminants in grains and cereals due to infection by enniatin-producing Fusarium species. This is the first article describing the transcriptional regulation of esyn1 gene that modulates ENs production in Fusarium avenaceum and provides new knowledge about the molecular mechanism underlying the biosynthesis of these important fungal metabolites in this toxigenic fungal species.

Heritability of arterial stiffness and carotid intima-media thickness: an Italian twin study.

BACKGROUND AND AIMS: Carotid intima-media thickness (IMT) and arterial stiffness parameters, including aortic augmentation index (AIx) and pulse wave velocity (PWV), are independent predictors of stroke and cardiovascular disease. Genetic effects on these traits were never explored in a Mediterranean country. The present study aims to quantify the contribution of genes, environment and age to carotid IMT and aortic Aix and PWV. METHODS AND RESULTS: The twin design was used. A total of 348 adult twins from the Italian Twin Register underwent measurements of carotid IMT and aortic PWV and AIx in three university hospitals located in Rome, Padua and Perugia. Carotid IMT was measured by B-mode ultrasound, aortic PWV and AIx by Arteriograph. Genetic modelling was performed to decompose total variance of traits into genetic, shared and unshared environmental and age components. For each phenotype, the best-fitting model included additive genetic, unshared environmental and age effects. For IMT, heritability was 0.32 (95% confidence interval (CI): 0.25-0.38), unshared environmental component was 0.25 (0.18-0.32) and age contribution was 0.44 (0.39-0.49). For AIx and PWV, heritabilities were 0.42 (0.29-0.55) and 0.49 (0.35-0.62), unshared environmental components were 0.31 (0.22-0.44) and 0.37 (0.26-0.51) and age contributions were 0.27 (0.16-0.39) and 0.14 (0.06-0.24), respectively. CONCLUSION: This study shows substantial genetic and unshared environmental influences on carotid intima-media thickness and arterial stiffness and confirms the relevant role of age in the aetiology of these traits. Further support is provided for prevention and health promotion strategies based on modifiable factors.

Congenital toxoplasmosis and audiological outcome: from a case series to a suggestion of patient-based schedule.

Introduction: Sensorineural hearing loss (SNHL) has been suggested to be possibly related to congenital toxoplasmosis (CT), although its prevalence varies from 0% to 26%. This variance appears to be dependent especially on early timing of treatment. However, the available data are based on outdated studies conducted on small groups of patients that lack homogeneity. Therefore, to establish evidence-based guidelines for audiologic monitoring in CT, we conducted a comprehensive evaluation of a large case series over a long period of time. Patients and methods: This is a single-center, retrospective cohort that enrolled all infants and children who were exposed in utero to Toxoplasma gondii and/or congenitally infected between September 1980 and December 2022. They underwent standard serial audiological evaluations to detect possible SNHL at an early stage. The first evaluation was performed during the initial assessment to define the onset of congenital toxoplasmosis, with another evaluation conducted at least at 12 months of life. Results: We collected data from 1,712 patients, and 183 (10.7%) were diagnosed with CT. Among these cases, 78 children (42.6%) presented with symptomatic CT at the onset, exhibiting ocular findings (21.1%), clinical cerebral manifestations (6.1%), and/or abnormal findings on neuroimaging (35.5%). Therapy was administrated at the onset in 164 patients (89.6%) with 115 of them starting treatment prior to 2.5 months of age (0-388, median 32.00 ± 92.352 days of life). Only one patient presented with SNHL at the onset, but this was apparently unrelated to CT. The median number of audiological assessments was 2.2 ± 1.543 (2-10). No patients developed any grade of delayed hearing loss, both in treated and untreated groups. The median age at last audiological evaluation was 2.3 ± 2.18 years (1-8), although the median follow-up period was 12.4 years (±6.3), ranging from 1 to 27 years. Conclusions: Based on these data, it appears that SNHL may be less frequent in CT than previously assumed. We recommend conducting an audiological assessment at the onset (within the first 2.5 months of life) to comprehensively define the type of CT onset, and then conducting another evaluation within 9 months of life.

Prospective comparative analysis of colour-Doppler ultrasound, contrast-enhanced ultrasound, computed tomography and magnetic resonance in detecting endoleak after endovascular abdominal aortic aneurysm repair.

OBJECTIVES: To assess the accuracy of colour-Doppler ultrasound (CDUS), contrast-enhanced ultrasonography (CEUS), computed tomography angiography (CTA) and magnetic resonance angiography (MRA) in detecting endoleaks after endovascular abdominal aortic aneurysm repair (EVAR). DESIGN: Prospective, observational study. MATERIALS AND METHODS: From December 2007 to April 2009, 108 consecutive patients who underwent EVAR were evaluated with CDUS, CEUS, CTA and MRA as well as angiography, if further treatment was necessary. Sensitivity, specificity, accuracy and negative predictive value of ultrasound examinations were compared with CTA and MRA as the reference standards, or with angiography when available. RESULTS: Twenty-four endoleaks (22%, type II: 22 cases, type III: two cases) were documented. Sensitivity and specificity of CDUS, CEUS, CTA, and MRA were 58% and 93%, 96% and 100%, 83% and 100% and 96% and 100% respectively. CEUS allowed better classification of endoleaks in 10, two and one patients compared with CDUS, CTA and MRA, respectively. CONCLUSIONS: The accuracy of CEUS in detecting endoleaks after EVAR is markedly better than CDUS and is similar to CTA and MRA. CEUS seems to be a feasible tool in the long-term surveillance after EVAR, and it may better classify endoleaks missed by other imaging techniques.

Low-dose contrast-enhanced time-resolved MR angiography at 3T: diagnostic accuracy for treatment planning and follow-up of vascular malformations.

AIM: To assess the accuracy of low-dose contrast-enhanced time-resolved 3T magnetic resonance angiography (MRA) for the morphological and functional assessment of vascular malformations (VM), and to evaluate its diagnostic potential for the depiction of treatment-induced changes. MATERIALS AND METHODS: Twenty-five patients with known VM underwent MRA to evaluate the location and extent of lesions and their haemodynamic characteristics. Three-dimensional (3D) T1-weighted time-resolved sequences were acquired following the administration of 0.05mmol/kg of gadobenate dimeglumine. VM were classified according to their morphology and haemodynamic characteristics. All patients thereafter underwent conventional angiography to confirm the diagnosis and to treat the lesions (embolization or sclerotherapy). Follow-up MRA was performed 30 days after treatment to assess morphological and functional changes. A visual analogue scale (VAS) was used to clinically assess the severity of symptoms before and after therapy. RESULTS: Based on haemodynamic characteristics, VM were classified as predominantly arterial [4 (16%)], artero-venous [19 (76%)] or venous [2 (8%)]. Twenty-three (92%) lesions were classified as high-flow VM and two (8%) as low-flow VM. Intralesional thrombosis was present in 17 (68%) lesions before therapy and in 10 lesions (40%) after therapy. The median VAS scores were 5±1 before treatment and 4±2 after treatment. Very good correlation (Spearman's correlation coefficient: rho=0.87; p=0.000) was noted between the reduction of lesion size on follow-up MRA and pain relief as assessed by VAS. CONCLUSION: Low-dose contrast-enhanced time-resolved 3T MRA can be used to define morphological and functional aspects of VM accurately during treatment planning and follow-up, and can identify post-therapy changes that positively correlate with treatment outcome.

Basal insulin-like factor 3 levels predict functional ovarian hyperandrogenism in the polycystic ovary syndrome.

AIM: The aims of the study were to understand the association between insulin-like factor 3 (INSL3) and functional ovarian hyperandrogenism (FOH) in PCOS and the regulatory role played by LH. SUBJECTS AND METHODS: Fifteen PCOS women were classified as FOH (FOH-PCOS, no.=8) and non-FOH (NFOH-PCOS, no.=7) according to the response of 17OH-progesterone to buserelin (a GnRH analogue) with respect to 15 controls. FOH-PCOS and NFOH-PCOS were compared for basal INSL3 levels. In addition, the effect of buserelin on INSL3 concentrations and the relationship between basal and buserelin-stimulated LH and 17OH-progesterone and INSL3 were evaluated. RESULTS: Basal INSL3 levels were higher in FOH-PCOS than NFOH-PCOS (p=0.001) and controls (p=0.001), whereas they did not differ between NFOHPCOS and controls. In addition, FOH-PCOS had a higher response of LH to buserelin with respect to NFOH-PCOS. Within all PCOS women the levels of INSL3 positively correlated with free testosterone (p=0.022) and negatively with SHBG (r= p=0.031). Moreover, positive correlations with the absolute increase of 17OH-progesterone (p<0.001) and with the LH area under the curve (p=0.001) after buserelin administration were found. In the multiple regression analysis INSL3 persisted significantly correlated only with 17OH-progesterone response to buserelin. Finally, INSL3 was not significantly modified after buserelin administration either in FOHPCOS or in NFOH-PCOS. CONCLUSIONS: These data suggest that INSL3 is related to FOH in PCOS women, but this association seems not to be mediated by LH, further reinforcing the concept that a pathophysiological heterogeneity for ovarian hyperandrogenism in PCOS exists.

Chlamydophila pneumoniae infection in patients undergoing carotid artery stent.

Although several reports have correlated Chlamydophila pneumoniae (CP) infection with carotid endarterectomy and coronary stent, no data have been reported on the potential relationship between this pathogen and carotid artery stenting (CAS). Hence, we evaluated 47 subjects, 27 symptomatic and 20 asymptomatic, before CAS intervention and during the follow up, for the presence of CP DNA and anti-CP antibodies, including chlamydial HSP60 (Cp-HSP60). Before stent placement, CP DNA was detected exclusively in symptomatic patients, all of whom were also positive for CP IgG and IgA and 85.7 percent of them also had CP-HSP60 antibodies. At the follow-up, all CP DNA positive and 11 out of the 13 symptomatic patients with Cp-HSP60 antibodies became negatives. In contrast, no change was observed for CP- IgA antibodies. Despite the small number of patients, the present study advocates an important role of CP infection in symptomatic patients with carotid artery disease. Our findings also suggest that stent placement and/or therapy might have a role in favouring resolution of inflammation, though not affecting persistence of CP infection.

Lipid metabolism impairment in human gliomas: expression of peroxisomal proteins in human gliomas at different grades of malignancy.

Gliomas are histologically graded by cellularity, cytological atypia, necrosis, mitotic figures, and vascular proliferation, features associated with biologically aggressive behaviour. However, abundant evidence suggests the presence of unrecognized, clinically relevant subclasses of the diffuse gliomas, both in respect to their underlying molecular phenotype and their clinical response to therapy. It is well-known that patient prognosis and therapeutic decisions rely on accurate pathological grading. Recently, it was reported that human gliomas accumulate lipid droplets during progression, suggesting a lipid metabolism impairment. Considering the crucial role of peroxisomes in lipid metabolism, in the present work we studied the expression profiles of proteins either exclusively localized to peroxisomes, such as peroxin14 (PEX14), peroxisomal membrane protein 70Kda (PMP70), acyl-CoA oxidase, thiolase, or partially associated to peroxisomes such as Hydroxymethylglutaryl-CoA reductase (HMGCoA-red) and peroxisomal-related proteins, namely PPARalpha, in human glioma specimens at different grades of malignancy. Moreover, Nile red staining of lipid droplets, thin layer chromatography (TLC) and proton nuclear magnetic resonance spectroscopy (NMR) were carried out in order to correlate the biochemical results with the lipid content of tumor tissues. The results obtained indicate that correlating the malignancy grade with the expression of peroxisomal genes and proteins, may constitute a sensitive tool to highlight possible subtypes not recognized by the classical histological techniques.

A closer look to the new frontier of artificial intelligence in the percutaneous treatment of primary lesions of the liver.

The purpose of thermal ablation is induction of tumor death by means of localized hyperthermia resulting in irreversible cellular damage. Ablative therapies are well-recognized treatment modalities for HCC lesions and are considered standard of care for HCC nodules < 3 cm in diameter in patients not suitable for surgery. Effective lesion treatment rely on complete target volume ablation. Technical limitations are represented by large (> 3 cm) or multicentric nodules as well as complex nodule location and poor lesion conspicuity. Artificial Intelligence (AI) is a general term referred to computational algorithms that can analyze data and perform complex tasks otherwise prerogative of Human Intelligence. AI has a variety of application in percutaneous ablation procedures such as Navigational software, Fusion Imaging, and robot-assisted ablation tools. Those instruments represent relative innovations in the field of Interventional Oncology and promising strategies to overcome actual limitations of ablative therapy in order to increase feasibility and technical results. This work aims to review the principal application of Artificial Intelligence in the percutaneous ablation of primary lesions of the liver with special focus on how AI can impact in the treatment of HCC especially on potential advantages on the drawbacks of the conventional technique.

Muscle myostatin signalling is enhanced in experimental cancer cachexia.

BACKGROUND/AIMS: Myostatin belongs to the transforming growth factor-beta superfamily and negatively regulates skeletal muscle mass. Its deletion induces muscle overgrowth, while, on the contrary, its overexpression or systemic administration cause muscle atrophy. The present study was aimed at investigating whether muscle depletion as occurring in an experimental model of cancer cachexia, the rat bearing the Yoshida AH-130 hepatoma, is associated with modulations of myostatin signalling and whether the cytokine tumour necrosis factor-alpha may be relevant in this regard. MATERIALS AND METHODS: Protein levels of myostatin, follistatin (myostatin endogenous inhibitor) and the activin receptor type IIB have been evaluated in the gastrocnemius of tumour-bearing rats by Western blotting. Circulating myostatin and follistatin in tumour hosts were evaluated by immunoprecipitation, while the DNA-binding activity of the SMAD transcription factors was determined by electrophoretic-mobility shift assay. RESULTS: In day 4 tumour hosts muscle myostatin levels were comparable to controls, yet follistatin was reduced, and SMAD DNA-binding activity was enhanced. At day 7, both myostatin and follistatin increased in tumour bearers, while SMAD DNA-binding activity was unchanged. To investigate whether tumour necrosis factor-alpha contributed to induce such changes, rats were administered pentoxifylline, an inhibitor of tumour necrosis factor-alpha synthesis that partially corrects muscle depletion in tumour-bearing rats. The drug reduced both myostatin expression and SMAD DNA-binding activity in day 4 tumour hosts and up-regulated follistatin at day 7. CONCLUSIONS: These observations suggest that myostatin pathway should be regarded as a potential therapeutic target in cancer cachexia.

Application of a recombinant laccase-chlorogenic acid system in protein crosslink and antioxidant properties of the curd.

Milk protein crosslink through the action of enzymes represents a feasible strategy to impart new functionalities to cheese. In this work we reported the effects of a laccase mediator system (LMS) on protein crosslink and antioxidant property of curd. The crosslinking activity of a purified recombinant laccase Ery4 and a commercial enzyme preparation (cLC), with three mediators was firstly evaluated in milk and then applied before curd manufacture. Only Ery4-LMS significantly increased curd weight compared to that of the control sample. SDS-PAGE revealed that similar high molecular weight bands produced by both LMSs in milk were also retained in curds. The antioxidant activity recorded in curds with Ery4-LMS was the highest among all samples both before and after gastro-pancreatic digestion. This is the first time that a CGA-based LMS is used in manufacture of curd with improved antioxidant properties. These results open new perspectives for dairy applications.

Dimerization of the lutropin receptor: insights from computational modeling.

A computational approach based upon rigid-body docking, ad hoc filtering, and cluster analysis has been carried out to predict likely interfaces in LHR homodimers. Quaternary structure predictions emphasize the role of helices 4, 5 and 6, with prominence to helix 4, in mediating inter-monomer interactions. Intermolecular interactions essentially involve the transmembrane domains rather than the hydrophilic loops and do not implicate disulfide bridges.Collectively, molecular dynamics simulations on the isolated receptor and computational modeling of LHR homodimerization suggest that mutation-induced LHR activation favors H4-H4 contacts involving the highly conserved W491 from both the receptors monomers.