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.
•Primary hyperparathyroidism (PHPT) is a common cause of secondary osteoporosis in postmenopausal women•In PHPT postmenopausal women the negative effect of estrogen withdrawal and that of hyperparathyroidism on bone coexist•Circulating microRNAs (miRNAs) expression profile has been correlated to both osteoporosis and fragility fractures•Circulating miRNA profiles, in particular miR-93-5p, clearly distinguished PHPT from estrogen withdrawal-related osteoporosis•Circulating miRNA profiles may be regulated by PTH activity in postmenopausal PHPT women
ObjectiveAdalimumab 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.DesignCase–control, longitudinal.SettingSingle centre.ParticipantsPatient 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.InterventionsAll 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 measuresStandard 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.ResultsThe 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.ConclusionsHigh 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.
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.
•The first case of epilepsy with two missense mutations in cis in the SCN1A gene is reported.•A novel mutation missense mutation is reported.•The functional effect of the coexistence of two mutations ...on the same chromosome is documented.
Mutations in the SCN1A gene causing either loss or gain of function have been frequently found in patients affected by genetic epilepsy with febrile seizures plus (GEFS+) or Dravet syndrome (also named severe myoclonic epilepsy in infancy SMEI). By mutation screening of the SCN1A gene, we identified for the first time a case of two missense mutations in cis (p.Arg1525Gln;Thr297Ile) in all affected individuals of an Italian family showing GEFS+ and idiopathic generalized epilepsy (IGE). The p.Arg1525Gln mutation was not previously reported yet and was predicted to be pathological by prediction tools, whereas the p.Thr297Ile was already identified in patients showing SMEI. Functional studies revealed that the Nav1.1 channels harboring both mutations were characterized by a significant shift in the activation curve towards more positive potentials. Our data demonstrate that the p.Arg1525Gln represents a novel mutation in the SCN1A gene altering the channel properties in the co-presence of the p.Thr297Ile.
Atherosclerosis and osteoporosis are interrelated entities and share similar pathogenic mechanisms. Recent studies showed that key proteins of bone metabolism, such as osteoprotegerin (OPG) and ...osteopontin (OPN), are also involved in vascular atherosclerosis and calcifications. The carotid intima-media thickness (CA-IMT) is an early quantitative marker of generalized atherosclerosis. Aim of study was to investigate whether 12-months treatment with zoledronate (ZLN) or teriparatide (TPT) affects CA-IMT and circulating OPG and OPN levels. In this study, 11 postmenopausal osteoporotic women (aged 73, 70.5–74.5 years; median, range interquartile) treated with 5 mg/year iv ZLN; 9 postmenopausal osteoporotic women (aged 70, 62.5–73.5 years) treated with 20 µg/day sc TPT; and 10 aged-, body mass index (BMI)-, glycemic, and lipid profiles-matched, free from anti-osteoporotic and hypocholesterolemic drugs, controls were prospectively investigated at baseline and after 12 months. At baseline, median CA-IMT was similar in the three groups and increased after 12 months. CA-IMT increased significantly in TPT-treated patients (1.0, 0.8–1.2 vs 1.1, 0.9–15 mm, P = 0.04), though the change was minimal. After 12 months of treatment, CA-IMT positively correlated with alkaline phosphatase (ALP) levels (r = 0.767, P = 0.008) and negatively with high-density lipoprotein (HDL) cholesterol levels (r = −0.65, P = 0.03), suggesting interplay between active bone remodeling and lipid profile. At baseline and after 12 months, median serum OPG and OPN levels did not differ among the groups and did not correlate with changes in CA-IMT. In conclusion, ZLN and TPT treatments are safe on carotid walls in osteoporotic women with subclinical atherosclerosis; circulating OPG and OPN are not affected by long-term anti-osteoporotic treatments and do not correlate with CA-IMT.
Cross-sectional study.
To develop an Italian version of the Levels of Cognitive Functioning Assessment Scale (LOCFAS) and examine its reliability and validity.
Patients with acquired brain injury in ...an early post-coma state.
The original scale was translated from English to Italian using the guidelines set forth in the Translation and Cultural Adaptation of Patient Reported Outcomes Measures-Principles of Good Practice. Intra-rater reliability was examined using the intraclass correlation coefficient (ICC). Concurrent validity was evaluated using Pearson's correlation coefficients with some of the functional and disability components of the International Classification of Functioning, Disability and Health (ICF), excluding environmental factors.
The highly specialized neurorehabilitation department of "San Raffaele" Hospital, Cassino.
The Italian version of the LOCFAS (LOCFAS-I) was administered to 38 subjects from May 9, 2017 to August 31, 2017. The mean ± SD of the LOCFAS-I score was 3.05 ± 1.88. All LOCFAS-I items were either identical or similar in meaning to the original version's items. Test-retest reliability (ICC) was 0.996 (p<0.01). The Pearson correlation coefficient of the LOCFAS-I scores with some of the functional and disability components of the ICF was > 0.536 (p<0.01).
The LOCFAS-I was found to be reliable and a valid measurement tool for the assessment of cognitive functioning post-coma in the Italian population.
Abstract Background Early palliative care (EPC) in oncology has been shown to have a positive impact on clinical outcome, quality-of-care outcomes, and costs. However, the optimal way for activating ...EPC has yet to be defined. Methods This prospective, multicentre, randomised study was conducted on 207 outpatients with metastatic or locally advanced inoperable pancreatic cancer. Patients were randomised to receive ‘standard cancer care plus on-demand EPC’ (n = 100) or ‘standard cancer care plus systematic EPC’ (n = 107). Primary outcome was change in quality of life (QoL) evaluated through the Functional Assessment of Cancer Therapy – Hepatobiliary questionnaire between baseline (T0) and after 12 weeks (T1), in particular the integration of physical, functional, and Hepatic Cancer Subscale (HCS) combined in the Trial Outcome Index (TOI). Patient mood, survival, relatives' satisfaction with care, and indicators of aggressiveness of care were also evaluated. Findings The mean changes in TOI score and HCS score between T0 and T1 were −4.47 and −0.63, with a difference between groups of 3.83 (95% confidence interval CI 0.10–7.57) (p = 0.041), and −2.23 and 0.28 (difference between groups of 2.51, 95% CI 0.40–4.61, p = 0.013), in favour of interventional group. QoL scores at T1 of TOI scale and HCS were 84.4 versus 78.1 (p = 0.022) and 52.0 versus 48.2 (p = 0.008), respectively, for interventional and standard arm. Until February 2016, 143 (76.9%) of the 186 evaluable patients had died. There was no difference in overall survival between treatment arms. Interpretations Systematic EPC in advanced pancreatic cancer patients significantly improved QoL with respect to on-demand EPC.
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