186,406 research outputs found
Stretching the evidence behind tennis elbow: mobile app user guide
No full textHeales, LJ ORCiD: 0000-0002-4510-3324; Lastella, AM ORCiD: 0000-0003-1793-3811Tennis elbow (TE), formally known as lateral epicondylalgia, is a musculoskeletal condition associated with pain over the lateral elbow and histological changes of the common extensor tendon. Numerous treatments are advocated for this condition, with recent developments in the use of mobile technology now added to the list
Anticipation in Lynch Syndrome: Where We Are Where We Go
No full textLynch syndrome (LS) is the most common form of inherited predisposition to develop cancer mainly in the co- lon and endometrium but also in other organ sites. Germline mutations in DNA mismatch repair (MMR) gene cause the transmission of the syndrome in an autosomal dominant manner. The management of LS patients is complicated by the large variation in age at cancer diagnosis which requires these patients to be enrolled in surveillance protocol starting as early as in their second decade of life. Several environmental and genetic factors have been proposed to explain this phe- notypic heterogeneity, but the molecular mechanisms remain unknown. Although the presence of genetic anticipation in Lynch syndrome has been suspected since 15 years, only recently the phenomenon has been increasingly reported to be present in different cancer genetic syndromes including LS. While the biological basis of earlier cancer onset in succes- sive generations remains poorly known, recent findings point to telomere dynamics as a mechanism significantly contrib- uting to genetic anticipation in Lynch syndrome and in other familial cancers. In this review, we summarize the clinical and molecular features of Lynch syndrome, with a particular focus on the latest studies that have investigated the molecu- lar mechanisms of genetic anticipation
Waking up in the zone with sleep cycle
No full textLastella, AM ORCiD: 0000-0003-1793-3811; Sargent, C ORCiD: 0000-0001-5340-4701A user guide for the mobile application Sleep Cycle alarm clock
Comparative pharmacokinetic and pharmacodynamic evaluation of branded and generic formulations of meloxicam in healthy male volunteers
No full textMario Del Tacca,1,2 Giuseppe Pasqualetti,3 Giovanni Gori,1 Pasquale Pepe,1 Antonello Di Paolo,2 Marianna Lastella,2 Ferdinando De Negri,1 Corrado Blandizzi2 1Clinical Pharmacology Centre for Drug Experimentation, Pisa University Hospital, 2Department of Clinical and Experimental Medicine, 3Geriatrics Unit, University of Pisa, Pisa, Italy Purpose: The primary aim of the present study was to assess the pharmacokinetic bioequivalence between a generic formulation of meloxicam 15 mg tablets (Meloxicam Hexal) and its respective brand product (Mobic), in order to verify whether the generic product conforms to the regulatory standards of bioequivalence in the postmarketing setting. As a secondary exploratory aim, the pharmacodynamic effects of the two formulations were also evaluated by means of rating scales following hyperalgesia induced by cutaneous freeze injury. Subjects and methods: A single 15 mg dose of generic or branded meloxicam tablets was administered to 24 healthy male volunteers in a crossover fashion. Plasma samples, collected for 24 hours after dosing, were assayed for meloxicam concentration by a validated high-performance liquid chromatography method. Results: The analysis of pharmacokinetic parameters did not show any significant difference between the two meloxicam formulations: the 90% confidence intervals fell within the acceptance range of 80%–125% (0.84–1.16 for area under the curve [0–24], and 0.89–1.23 for peak concentration). No difference in the pharmacodynamic end point was observed between the two groups. Conclusion: The pharmacokinetic profiles of the two meloxicam formulations confirm the regulatory criteria for bioequivalence; pharmacodynamic data indicate a similar antihyperalgesic effect. The two formulations can be used interchangeably in the clinical setting. Keywords: meloxicam, pharmacokinetics, healthy volunteers, generic drug, bioequivalence, postmarketin
In silico and in vivo analysis of MLH1 and MSH2 missense mutations shows exon- and tissue-specific effects
No full textBackground: Abnormalities of pre-mRNA splicing are increasingly recognized as an important mechanism through which gene mutations cause disease. However, apart from the mutations in the donor and acceptor sites, the effects on splicing of other sequence variations are difficult to predict. Loosely defined exonic and intronic sequences have been shown to affect splicing efficiency by means of silencing and enhancement mechanisms. Thus, nucleotide substitutions in these sequences can induce aberrant splicing. Web-based resources have recently been developed to facilitate the identification of nucleotide changes that could alter splicing. However, computer predictions do not always correlate with in vivo splicing defects. The issue of unclassified variants in cancer predisposing genes is very important both for the correct ascertainment of cancer risk and for the understanding of the basic mechanisms of cancer gene function and regulation. Therefore we aimed to verify how predictions that can be drawn from in silico analysis correlate with results obtained in an in vivo splicing assay. Results: We analysed 99 hMLH1 and hMSH2 missense mutations with six different algorithms. Transfection of three different cell lines with 20 missense mutations, showed that a minority of them lead to defective splicing. Moreover, we observed that some exons and some mutations show cell-specific differences in the frequency of exon inclusion. Conclusion: Our results suggest that the available algorithms, while potentially helpful in identifying splicing modulators especially when they are located in weakly defined exons, do not always correspond to an obvious modification of the splicing pattern. Thus caution must be used in assessing the pathogenicity of a missense or silent mutation with prediction programs. The variations observed in the splicing proficiency in three different cell lines suggest that nucleotide changes may dictate alternative splice site selection in a tissue-specific manner contributing to the widely observed phenotypic variability in inherited cancers
Effects of traditional balance and slackline training on physical performance and perceived enjoyment in young soccer players
No full textLastella, AM ORCiD: 0000-0003-1793-3811The aim of this study was to evaluate the effects of 12-week balance and slackline training programs on physical performance and perceived enjoyment scale in young soccer players. Forty-one preadolescent soccer players were assigned to two experimental groups performing traditional balance (BLT) or slackline training (SLT), and a control group. Pre-post assessment encompassed Balance Error Scoring System (BESS), Star Excursion Balance test (SEBT), sprint with 90° turns (S90), and countermovement jump (CMJ). The rate of perceived enjoyment scale (PACES) was applied at the end of the experimental period. SLT and BLT improved similarly in BESS, SEBT and S90. No changes were detected in the CMJ. Regarding PACES score, SLT presented significantly higher values than BLT. Young athletes may benefit from a motivating training approach, thus, a designed program based on slackline drills should be preferable to improve physical performance in terms of balance and change of direction ability in preadolescent soccer players. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group
A 71-nucleotide deletion in the periaxin gene in an Italian patient with late-onset slowly progressive demyelinating CMT
No full textBackground: Charcot-Marie-Tooth disease (CMT) constitutes a group of heterogeneous hereditary motor and sensor neuropathies. Mutations in the periaxin (PRX) gene cause CMT4F with an autosomal recessive early-onset demyelinating neuropathy and are extremely rare in a non-Romani white population. Methods: We report on a 66-year-old Italian man presenting with slowly progressive and late-onset demyelinating CMT. The molecular analysis was performed using a custom panel containing 39 genes associated with the CMT phenotype. Results: The patient harbored a homozygous PRX 71-nucleotide deletion (c.3286_3356del71, I1096fsX17). Conclusions: This is the first report that describes such a genetic mutation in a population of non-Romani origin
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