Acute changes in free and extracellular vesicle-associated circulating miRNAs and myokine profile in professional sky-runners during the Gran Sasso d'Italia vertical run.

The modification of gene expression profile, a first step in adaptation to exercise, leads to changes in the level of molecules associated with skeletal muscle activity and energy metabolism-such as myokines-as well as those involved in their transcriptional regulation, like microRNA. This study aimed to investigate the influence of strenuous exercise on circulating microRNAs and their possible association with myokine response. Pre-competition and post-competition plasma samples were collected from 14 male athletes participating in a vertical run (+1,000 m gain, 3,600 m length). Circulating total (t-miRNA) and extracellular vesicle-associated (EV-miRNA) miRNAs were extracted from the pooled plasma. Nanoparticle tracking analysis was performed to investigate pre- and post-competition EV concentration and size distribution. A panel of 179 miRNAs was assayed by qPCR and analyzed by Exiqon GenEx v6 normalized on the global mean. t-miRNA and EV-miRNAs whose level was ≥5-fold up- or down-regulated were validated for each single subject. Target prediction on MirWalk v3.0, Gene-Ontology, and pathway enrichment analysis on Panther v17.0 were performed to define the potential biological role of the identified miRNAs. A panel of 14 myokines was assayed in each sample by a multiplex immunoassay. In whole plasma, five miRNAs were upregulated and two were downregulated; in the EV fraction, five miRNAs were upregulated and three were downregulated. Nanoparticle tracking analysis revealed a similar EV size distribution in pre- and post-competition samples and a decreased concentration in post-competition samples related to pre-competition samples. Gene-Ontology and pathway enrichment analysis revealed that the identified t-miRNAs and EV-miRNAs were potentially involved in metabolism regulation in response to exercise. Correlation between fold-change of the post-competition relative to pre-competition plasma level of both t-miRNAs and EV-miRNAs and myokines further confirmed these results. This study provides an example of a systemic response to acute endurance exercise, in which circulating miRNAs play a pivotal role.

Circulating fractures-related microRNAs distinguish primary hyperparathyroidism-related from estrogen withdrawal-related osteoporosis in postmenopausal osteoporotic women: A pilot study.

Primary hyperparathyroidism (PHPT) represents a common cause of secondary osteoporosis in postmenopausal women, where the negative effect of estrogen withdrawal and that of hyperparathyroidism on bone mineralization coexist. Circulating microRNAs (miRNAs) expression profile has been correlated to both osteoporosis and fragility fractures. The study aimed to profile a set of miRNAs associated with osteoporotic fractures, namely miR-21-5p, miR-23a-5p, miR-24-2-5p, miR-24-3p, miR-93-5p, miR-100-5p, miR-122-5p, miR-124-3p, miR-125b-5p and miR-148-3p, in the plasma of 20 postmenopausal PHPT women. PHPT miRNAs profiles were compared with those detected in 10 age-matched postmenopausal non-PHPT osteoporotic women (OP). All the 10 miRNAs were detected in the plasma samples of both PHPT and OP women. The miRNA profiles clearly distinguished PHPT from OP samples, and identified within the PHPT group, two clusters differing for the PHPT severity, in term of ionized calcium and bone mineralization. In particular, miR-93-5p was significantly downregulated in PHPT samples, while miR-24-3p negatively correlated with the T-score at lumbar, femur neck and total hip sites. PHPT women who experienced osteoporotic fractures had plasma miR-24-3p levels higher than those detected in unfractured PHPT women. In conclusion, PHPT may modulate circulating fractures-related miRNAs, in particular, miR-93-5p, which may distinguish estrogen-related from PHPT-related osteoporosis.

Anti-adalimumab antibodies in psoriasis: lack of clinical utility and laboratory evidence.

OBJECTIVE: Adalimumab has proven effective in psoriasis; however, secondary failure may result from the drug's immunogenicity. Prevalence data on the immunogenicity of biologicals, and of adalimumab in particular, are highly variable. We investigated the prevalence of anti-adalimumab antibodies and the association with clinical indexes and tumour necrosis factor α (TNFα) serum levels in psoriatic patients. DESIGN: Case-control, longitudinal. SETTING: Single centre. PARTICIPANTS: Patient groups: I (n=20) receiving biological therapies after switching from adalimumab; II (n=30) ongoing adalimumab therapy; III (n=30) novel adalimumab therapy; IV (n=15) biological therapies other than adalimumab.Healthy subjects: (group V; n=15) never treated with immunosuppressants or biologicals. INTERVENTIONS: All groups were tested at enrolment. Group II was also tested at 12 months, and group III at 1, 3, and 6 months. PRIMARY AND SECONDARY OUTCOME MEASURES: Standard clinical evaluations (Psoriasis Area Severity Index (PASI)), blood samples and two-site ELISA-based measurement of serum adalimumab trough levels, anti-adalimumab antibodies and TNFα. RESULTS: The false-positive rate was 23% for adalimumab detection and 22% for anti-adalimumab antibodies in patients naïve to adalimumab. Spurious positivity for anti-adalimumab antibodies (one-time-point positivity in group III during follow-up) accounted for 33% of the total. The prevalence of anti-drug antibodies was highest (87%) in group I patients. No correlations were found between the presence of anti-adalimumab antibodies or adalimumab levels and changes in PASI scores. CONCLUSIONS: High variability of results, high prevalence of false-positives and lack of association between anti-adalimumab antibodies and TNFα level/PASI score limit this assay's usefulness. Accurate clinical evaluation is key to early identification of treatment failures.

Perisurgical and intra-rehabilitative salivary steroid hormone profiles in bicompartmental arthroplasty.

Sex hormones play a role in pain perception, a key variable in evaluating the progression and treatment of osteoarthritis. The aim of this study was to determine the relationship between salivary concentrations of four steroid hormones and functional/clinical outcomes after hip and knee arthroplasty. Saliva samples were collected from 24 otherwise healthy patients with osteoarthritis before surgery, on admission to rehabilitation, and at hospital discharge. Salivary concentrations of testosterone, 17ß-estradiol, dehydroepiandrosterone (DHEA), and cortisol were immunoassayed. Changes in hormone levels were compared with clinical outcomes, as assessed by functional independence measure (FIM®), Barthel Index (BI), and visual analog scale for pain (VAS) scores. Changes in testosterone levels were significantly inversely correlated with VAS (r= -0.53, p=0.043) and FIM® and BI scores in all patients (r= -0.30, p= 0.043, and r= -0.35, p=0.031, respectively). The testosterone to cortisol ratio was inversely correlated with BI scores in all patients (r= -0.30, p=0.040), and in the men (r= -0.55, p=0.005) and the women (r= -0.28, p=0.042) when analyzed separately. Changes in salivary testosterone concentrations closely correlated with clinical outcome measurements for total hip and knee arthroplasty. Clinical outcome after arthroplasty was generally better among the men.

[Experience in risk assessment in variety type of work: reflection on reliability and judgement in method reference to European accord, 2004]. / Esperienze di valutazioni del rischio stress in realtà lavorative di varia tipologia: riflessioni sull'attendibilità e riproponibilità del metodo anche in riferimento all'accordo europeo del 2004.

Interest in problems of work-related stress has been limited, till now, to its effects on health of workers. The aim of our study, lacking valid literature's instruments, is to experiment and to evaluate a risk's evaluation model to identify and prevent or manage problems of work-related stress also according to indications published in "European Framework Agreement on work-related stress" (08/10/2004). Our evaluation model (even according to art. 28 D.Lgs. 81/2008) has been experimented in a sample composed by 1470 employers in 19 Lomabardia's factories. Valued risk's results have been introduced in the risk assessment and they have been used to sanitary surveillance indications.

High-dose epirubicin in the prophylactic treatment of T1G2 superficial bladder tumors.

OBJECTIVES: To evaluate the activity and safety of intravesical instillations of 80 mg epirubicin in a selected patient population with T1G2 primary and multiple superficial bladder tumors. To assess the completeness of the transurethral resection (TUR) at 4 weeks (second look) and to compare the histology of local and review pathology. METHODS: One hundred and sixty-nine patients have been histologically assessed both locally and extramurally for T1G2 superficial bladder tumors. Epirubicin (80 mg/instillation) started within 20 days after TUR was administered weekly during the first month and then monthly for another 11 months. Assessments for relapse were carried out according to the standard methods. RESULTS: Histological consistency for T1G2 between local and extramural assessments was found in 85.2% of cases. At the median follow-up time of 38 months, the overall relapse rate was 43.3%. Treatment was very well tolerated: no systemic adverse events were reported and local adverse events were confined to chemical cystitis which in 3% required treatment discontinuation. CONCLUSIONS: Epirubicin (80 mg/instillation) appeared effective in the prophylaxis of relapse in primary and multiple T1G2 superficial bladder tumors. A second TUR at 3-4 weeks is necessary in T1 tumors. Excellent concordance between local and review pathology was found.

[Extrinsic ureteral endometriosis: diagnostic laparoscopic contribution]. / Endometriosi ureterale estrinseca: contributo diagnostico laparoscopico.

A case of extrinsic ureteral endometriosis diagnosed with laparoscopy is described. Endometriosis, a common disease in premenopausal women, should be considered in differential diagnosis in patients with ureteral obstruction. Usually, the diagnosis of ureteral involvement is made at surgery. Laparoscopy is, therefore, an important diagnostic aid in women with distal ureteral obstruction not attributable to calculous.