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1.
Diagnostics (Basel) ; 11(3)2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33801055

RESUMO

Previous research involving epithelial ovarian cancer patients showed that, compared to germline BRCA (gBRCA) mutations, somatic BRCA (sBRCA) mutations present a similar positive impact with regard to overall survival (OS) and platinum and PARP (poly (ADP-ribose) polymerase) inhibitor sensitivity. Nevertheless, molecular testing in these studies did not include copy number variation (CNV) analyses of BRCA genes. The aim of this study was to explore the prognostic and predictive role of sBRCA mutations as compared to gBRCA mutations in patients who were also tested for CNVs. Among the 158 patients included in the study, 17.09% of patients carried a pathogenic or likely pathogenic gBRCA variant and 15.19% of patients presented pathogenetic or likely pathogenic sBRCA variants and/or CNVs. Overall, 81.6% of the patients included in this study were diagnosed with a serous histotype, and 77.2% were in advanced stages. Among women diagnosed in advanced stages, gBRCA patients showed better progression-free survival and OS as compared to sBRCA and wild-type patients, whereas sBRCA patients did not show any advantage in outcome as compared to wild-type patients. In this study, the introduction of CNV analyses increased the detection rate of sBRCA mutations, and the resulting classification among gBRCA, sBRCA and wild-type patients was able to properly stratify the prognosis of OC patients. Particularly, sBRCA mutation patients failed to show any outcome advantage as compared to wild-type patients.

2.
J Clin Med ; 10(7)2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33807327

RESUMO

BACKGROUND: Achilles tendinopathy (AT) affects ca. 10 million recreational runners in Europe; the practice of hyaluronic acid (HA) infiltration is being increasingly adopted. The aim of this pilot study was to monitor the effects of a three-local time-spaced injections regimen of HA in the treatment of AT in middle-aged runners combining for the first time viscoelastometric, biochemical, and functional methodologies with routine clinical examinations. METHODS: Eight male runners (Age 49.3 ± 3.9), diagnosed for unilateral AT, were given three ultrasound (US) guided peritendinous HA injections at the baseline (T0) and every fifteenth day with a follow-up on the forty-fifth day (T1, T2, and T3). At all-time points patients were assessed for viscoelastic tone and stiffness, maximal voluntary isometric contraction (MVIC), and pain level (Likert scale 0-5). The peritendinous effusions of the injured tendon were collected at T0 and T2 to quantify the volume variations and the IL-1ß and MMP-3 levels. RESULTS: At T0 MVIC and pain score were significantly lower and higher, respectively, in injured tendons. The volume, IL-1ß and MMP-3 levels decreased in the course of treatment and the clinical endpoints ameliorated over time. Tone, stiffness, and functional performance also varied significantly at T2 and T3, as compared to T0. CONCLUSIONS: The sequential peritendinous injections of HA were effective in the amelioration of the clinical symptoms, as well as of the functional and viscoelastic state associated with AT. The determination of the viscoelastometric state may help to precisely evaluate the healing process in AT patients.

3.
Cancer Biol Med ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33710808

RESUMO

OBJECTIVE: As prostate cancer (PrC) shows a BRCA mutation rate as high as 30%, it becomes crucial to find the optimal selection criteria for genetic testing. The primary objective of this study was to evaluate the BRCA mutation rate in families with PrC associated with breast and/or ovarian cancers; secondary aims were to compare the characteristics of families and BRCA-related PrC outcome among BRCA1 and BRCA2 carriers. METHODS: Following the Modena criteria for the BRCA test, we evaluated the mutation rate in families with breast and/or ovarian cancer with a Gleason score ≥7 PrCs, by testing breast or ovarian cases and inferring the mutation in the prostate cases. The characteristics of families and BRCA-related PrC outcomes were measured using the chi-square (χ2) test and Kaplan-Meier methods, respectively. RESULTS: Among 6,591 families, 580 (8.8%) with a Gleason score ≥ 7 PrCs were identified, of which 332 (57.2%) met the Modena selection criteria for BRCA testing. Overall, 215 breast or ovarian cancer probands (64.8%) were tested, of which 41 resulted positive for BRCA and one for CHEK2 genes (19.5%). No statistically significant differences were found in BRCA-related PrC prognosis and in the characteristics of families among BRCA1, BRCA2 and non-tested patients. Ten of 23 (44%) mutations in the BRCA2 gene fell in the prostate cancer cluster region (PCCR) at the 3´ terminal of the 7914 codon. CONCLUSIONS: It appears the Modena criteria are very useful for BRCA testing selection in families with breast and/or ovarian cancer and PrC. A trend toward a worse prognosis has been found in BRCA2 carriers.

4.
Nutrients ; 13(2)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33535496

RESUMO

Cancer is often accompanied by worsening of the patient's iron profile, and the resulting anemia could be a factor that negatively impacts antineoplastic treatment efficacy and patient survival. The first line of therapy is usually based on oral or intravenous iron supplementation; however, many patients remain anemic and do not respond. The key might lie in the pathogenesis of the anemia itself. Cancer-related anemia (CRA) is characterized by a decreased circulating serum iron concentration and transferrin saturation despite ample iron stores, pointing to a more complex problem related to iron homeostatic regulation and additional factors such as chronic inflammatory status. This review explores our current understanding of iron homeostasis in cancer, shedding light on the modulatory role of hepcidin in intestinal iron absorption, iron recycling, mobilization from liver deposits, and inducible regulators by infections and inflammation. The underlying relationship between CRA and systemic low-grade inflammation will be discussed, and an integrated multitarget approach based on nutrition and exercise to improve iron utilization by reducing low-grade inflammation, modulating the immune response, and supporting antioxidant mechanisms will also be proposed. Indeed, a Mediterranean-based diet, nutritional supplements and exercise are suggested as potential individualized strategies and as a complementary approach to conventional CRA therapy.

5.
Menopause ; 28(3): 263-270, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33534430

RESUMO

OBJECTIVE: BRCA carriers are recommended to undergo prophylactic risk-reducing salpingo-oophorectomy (RRSO). Possible adverse health impacts of RRSO, particularly when done before natural menopause, can reduce the long-term satisfaction with this risk-reducing strategy. The aim of this study was to prospectively evaluate the level of satisfaction of women undergoing RRSO, also in relation to some specific characteristics at RRSO. METHODS: A prospective cohort study was performed in the Modena Family Cancer Clinic of the University Hospital of Modena (Italy). All BRCA1/2 confirmed mutation carriers who decided to undergo RRSO were recruited between 2016 and 2019. RESULTS: Fifty-five women (29 BRCA1 and 26 BRCA2) (mean age: 50.4 ±â€Š7.7 years [range 35-79]) were included with a mean follow-up after RRSO of 660.9 days (1.8 years) (range 35-1,688 days) (median: 549 days). No intraepithelial (Serous Tubal Intraepithelial Carcinoma)/invasive cancers were found (0%) at RRSO. No vasomotor symptoms at 1 month after surgery were reported by 11/22 (50%) premenopausal women at RRSO. All women (100%) with new "RRSO-caused" vasomotor symptoms with no previous breast cancer initiated postmenopausal hormone therapy. At the final follow-up the satisfaction rate (0-100 visual analog scale points) of the participants was 96.4 ±â€Š8.6 points (range 62-100). To the question "Would you undergo RRSO again if it was proposed today? (0-100 visual analog scale points)" the answer was 99.4 ±â€Š3.2 points (range 79-100). These scores were in general very high and did not change in the different groups according to pre/postmenopausal status at RRSO, cancer survivors versus healthy women at RRSO, BRCA status, hormone therapy users/nonusers after RRSO, "RRSO-caused" symptoms versus not RRSO-caused (P > 0.05). CONCLUSIONS: Findings from this prospective study suggest that satisfaction with RRSO is very high and little dependent on the participants' characteristics at surgery. Women at high risk for ovarian cancer are very satisfied with their choice of risk-reduction strategy.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/prevenção & controle , Ovariectomia/efeitos adversos , Ovariectomia/métodos , Satisfação Pessoal , Procedimentos Cirúrgicos Profiláticos/efeitos adversos , Salpingectomia/métodos , Salpingo-Ooforectomia/efeitos adversos , Adulto , Idoso , Proteína BRCA1/metabolismo , Proteína BRCA2/metabolismo , Neoplasias da Mama/patologia , Feminino , Humanos , Itália , Pessoa de Meia-Idade , Mutação , Neoplasias Ovarianas/patologia , Estudos Prospectivos , Comportamento de Redução do Risco , Resultado do Tratamento
6.
Genes (Basel) ; 12(2)2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33494414

RESUMO

Next-generation sequencing (NGS)-based cancer risk screening with multigene panels has become the most successful method for programming cancer prevention strategies. ATM germ-line heterozygosity has been described to increase tumor susceptibility. In particular, families carrying heterozygous germ-line variants of ATM gene have a 5- to 9-fold risk of developing breast cancer. Recent studies identified ATM as the second most mutated gene after CHEK2 in BRCA-negative patients. Nowadays, more than 170 missense variants and several truncating mutations have been identified in ATM gene. Here, we present the molecular characterization of a new ATM deletion, identified thanks to the CNV algorithm implemented in the NGS analysis pipeline. An automated workflow implementing the SOPHiA Genetics' Hereditary Cancer Solution (HCS) protocol was used to generate NGS libraries that were sequenced on Illumina MiSeq Platform. NGS data analysis allowed us to identify a new inactivating deletion of exons 19-27 of ATM gene. The deletion was characterized both at the DNA and RNA level.

7.
Neuropsychologia ; 151: 107728, 2021 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-33326758

RESUMO

Evidence from psycholinguistic research indicates that sentence processing is impaired in Primary Progressive Aphasia (PPA), and more so in individuals with agrammatic (PPA-G) than logopenic (PPA-L) subtypes. Studies have mostly focused on offline sentence production ability, reporting impaired production of verb morphology (e.g., tense, agreement) and verb-argument structure (VAS) in PPA-G, and mixed findings in PPA-L. However, little is known about real-time sentence comprehension in PPA. The present study is the first to compare real-time semantic, morphosyntactic and VAS processing in individuals with PPA (10 with PPA-G and 9 with PPA-L), and in two groups of healthy (22 young and 19 older) individuals, using event-related potentials (ERP). Participants were instructed to listen to sentences that were either well-formed (n = 150) or contained a violation of semantics (e.g., *Owen was mentoring pumpkins at the party, n = 50), morphosyntax (e.g., *The actors was singing in the theatre, n = 50) or VAS (*Ryan was devouring on the couch, n = 50), and were required to perform a sentence acceptability judgment task while EEG was recorded. Results indicated that in the semantic task both healthy and PPA groups showed an N400 response to semantic violations, which was delayed in PPA and older (vs. younger) groups. Morphosyntactic violations elicited a P600 in both groups of healthy individuals and in PPA-L, but not in PPA-G. A similar P600 response was also found only in healthy individuals for VAS violations; whereas, abnormal ERP responses were observed in both PPA groups, with PPA-G showing no evidence of VAS violation detection and PPA-L showing a delayed and abnormally-distributed positive component that was negatively associated with offline sentence comprehension scores. These findings support characterizations of sentence processing impairments in PPA-G, by providing online evidence that VAS and morphosyntactic processing are impaired, in the face of substantially preserved semantic processing. In addition, the results indicate that on-line processing of VAS information may also be impaired in PPA-L, despite their near-normal accuracy on standardized language tests of argument structure production.

8.
Neurocase ; 27(1): 39-56, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33378229

RESUMO

This study reports the results of a longitudinal study examining the effects of treatment for sentence processing deficits for a 70-year-old gentleman (DK) with the agrammatic variant of Primary Progressive Aphasia (PPA). On entry into the study, he presented with a 2-year history of impaired verb and sentence processing and concomitant neural atrophy in primarily subcortical regions. Spanning an 18-month period, treatment focused on improving comprehension and production of syntactically complex, passive and object cleft, structures, consecutively. Results, derived from extensive behavioral and neurocognitive testing, showed not only improved ability to comprehend and produce both trained and untrained, less complex, linguistically related structures in offline tasks, but also improved online sentence processing strategies as revealed by partially normalized eye movements in online comprehension (i.e., emergence of thematic prediction and thematic integration) and production (i.e., use of incremental processing) tasks. Changes in neural activation from pre- to post-treatment of both structures also were found, with upregulation of tissue in both the left and right hemispheres, overlapping with regions recruited by neurotypical adults performing the same task. These findings indicate that Treatment of Underlying Forms (TUF) is effective for treatment of patients with the agrammatic variant of PPA (as it is for those with stroke-induced agrammatism), and show that unaffected neural tissue in patients with PPA is malleable and may be recruited to support language, providing evidence of experience-based plasticity in neurodegenerative disease.

9.
Neuropsychologia ; : 107713, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33285187

RESUMO

PURPOSE: This study examined grammatical production impairments in primary progressive aphasia (PPA), as measured by structured tests and narrative samples. We aimed to quantify the strength of the relationship between grammatical measures across tasks, and identify factors that condition it. Three grammatical domains were investigated: overall sentence production, verb morphology, and verb-argument structure. METHODS: 77 participants with PPA (34 PPA-G, 16 PPA-L, 15 PPA-S and 12 other) completed a battery of grammatical tests and a narrative language sample was obtained. Accuracy scores were computed for the language tests and the narrative samples were analyzed for both accuracy of selected narrative variables as well as grammatical diversity across the three grammatical domains. Principal components analysis (PCA) and multiple regression were used to examine cross-task relationships for all measures. RESULTS: As expected on the basis of classification criteria, accuracy scores were lower for the PPA-G group as compared to the PPA-L and PPA-S participants for overall sentence production and verb morphology, but not argument structure. Grammatical accuracy in narratives strongly predicted overall language test performance in PPA-G, whereas grammatical diversity in narratives did so in PPA-L, and no significant correspondence between narrative and language test performance was found for PPA-S. For individuals with severe grammatical impairments only, error distribution for both morphology and argument structure was strongly associated in structured tasks and narratives. CONCLUSIONS: Grammatical production in narrative language predicts accuracy elicited with structured language tests in PPA. However, unique narrative production patterns distinguish PPA by subtype: accuracy for PPA-G, and grammatical diversity for PPA-L. The impairment in PPA-G is likely to reflect a core impairment in grammar whereas that of PPA-L may be closely tied to the word retrieval and verbal working memory deficits that characterize this variant. This underscores the theoretical distinction between PPA-L and PPA-G, as well as the importance of including grammatical diversity measures in analyses of language production, especially for patients who do not display frank agrammatism. Further, the results suggest that measures of domain-specific language deficits (i.e., verb morphology vs. argument structure) are robust across tasks only in individuals with severe grammatical impairments.

11.
Neuroimage ; 224: 117374, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32949711

RESUMO

Functional neuroimaging and lesion-symptom mapping investigations implicate a left frontal-temporal-parietal network for sentence processing. The majority of studies have focused on sentence comprehension, with fewer in the domain of sentence production, which have not fully elucidated overlapping and/or unique brain structures associated with the two domains, particularly for sentences with noncanonical word order. Using voxel-based lesion symptom mapping (VLSM) we examined the relationship between lesions within the left hemisphere language network and both sentence comprehension and production of simple and complex syntactic structures in 76 participants with chronic stroke-induced aphasia. Results revealed shared regions across domains in the anterior and posterior superior temporal gyri (aSTG, pSTG), and the temporal pole (adjusted for verb production/comprehension). Additionally, comprehension was associated with lesions in the anterior and posterior middle temporal gyri (aMTG, pMTG), the MTG temporooccipital regions, SMG/AG, central and parietal operculum, and the insula. Subsequent VLSM analyses (production versus comprehension) revealed critical regions associated with each domain: anterior temporal lesions were associated with production; posterior temporo-parietal lesions were associated with comprehension, implicating important roles for regions within the ventral and dorsal stream processing routes, respectively. Processing of syntactically complex, noncanonical (adjusted for canonical), sentences was associated with damage to the pSTG across domains, with additional damage to the pMTG and IPL associated with impaired sentence comprehension, suggesting that the pSTG is crucial for computing noncanonical sentences across domains and that the pMTG, and IPL are necessary for re-analysis of thematic roles as required for resolution of long-distance dependencies. These findings converge with previous studies and extend our knowledge of the neural mechanisms of sentence comprehension to production, highlighting critical regions associated with both domains, and further address the mechanism engaged for syntactic computation, controlled for the contribution of verb processing.

12.
Eur J Appl Physiol ; 120(12): 2677-2691, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32909059

RESUMO

PURPOSE: To compare the effect of high-intensity aerobic (AER), resistance (RES), and combined (COMB: RES + AER) exercise, on interstitial glucose (IG) variability and skeletal muscle signalling pathways in type 1 diabetes (T1D). METHODS: T1D participants (6 M/6F) wore a flash glucose monitoring system in four randomized sessions: one control (CONT), and one AER, RES and COMB (40 min each). Mean amplitude of glycemic excursions (MAGE), standard deviation (SD) and coefficient variation (CV) of IG were used to compare the 24 h post-exercise IG variability. Blood and muscle samples were collected to compare exercise-induced systemic and muscle signalling responses related to metabolic, growth and inflammatory adaptations. RESULTS: Both RES and COMB decreased the 24 h MAGE compared to CONT; additionally, COMB decreased the 24 h SD and CV. In the 6-12 h post-exercise, all exercise modalities reduced the IG CV while SD decreased only after COMB. Both AER and COMB stimulated the PGC-1α mRNA expression and promoted the splicing of IGF-1Ea variant, while Akt and p38MAPK phosphorylation increased only after RES and COMB. Additionally, COMB enhanced eEF2 activation and RES increased myogenin and MRF4 mRNA expression. Blood lactate and glycerol levels and muscle IL-6, TNF-α, and MCP-1 mRNAs increased after all exercise sessions, while serum CK and LDH level did not change. CONCLUSION: COMB is more effective in reducing IG fluctuations compared to single-mode AER or RES exercise. Moreover, COMB simultaneously activates muscle signalling pathways involved in substrate metabolism and anabolic adaptations, which can help to improve glycaemic control and maintain muscle health in T1D.

13.
Sci Rep ; 10(1): 10929, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32616849

RESUMO

The southern surf crab Ovalipes trimaculatus (de Haan, 1833) presents a high potential for aquaculture. In this study, we analyze the benefits of different dietary treatments on its molt success and fitness of larval stages. Artemia persimilis nauplii were enriched with monospecific (Nannochloropsis oculata, Tetraselmis suecica, Dunaliella salina, Isochrysis galbana and Chaetoceros gracilis) and multispecific (Mix) microalgal diets twice a day over a 48-h period. Mean total length (TL), growth instar number (I) and gut fullness rate (GFR) of nauplii showed significant differences between dietary treatments at several sampling times, optimal results being observed in those providing Mix. Artemia nauplii grown under most experimental dietary treatments reached the capture size limit for Ovalipes trimaculatus zoea I (700 µm) within 24 h. After that time interval, Mix-enriched nauplii were amongst those with higher protein contents. Ovalipes trimaculatus zoea I fed on Artemia nauplii enriched during 24 h under different dietary treatments showed significant differences in survival, inter-molt duration, molting success to zoea II and motility. Optimal results were observed in zoea I fed on Mix-enriched Artemia nauplii. This work not only represents a first step towards the dietary optimization for O. trimaculatus zoeae rearing but also provides the first results on the use of enriched A. persimilis.

14.
Cancers (Basel) ; 12(5)2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32429297

RESUMO

NCCN Guidelines recommend BRCA genetic testing in individuals with a probability >5% of being a carrier. Nonetheless, the cost-effectiveness of testing individuals with no tumor family history is still debated, especially when BRCA testing is offered by the national health service. Our analysis evaluated the rate of BRCA pathogenic or likely-pathogenic variants in 159 triple-negative breast cancer (TNBC) patients diagnosed ≤60 years, and 109 luminal-like breast cancer (BC) patients diagnosed ≤35 without breast and/or ovarian family histories. In TNBC patients, BRCA mutation prevalence was 22.6% (21.4% BRCA1). Mutation prevalence was 64.2% ≤30 years, 31.8% in patients aged 31-40, 16.1% for those aged 41-50 and 7.9% in 51-60s. A total of 40% of patients with estrogen receptors (ER) 1-9% were BRCA1 carriers. BRCA detection rate in early-onset BCs was 6.4% (4.6% BRCA2). Mutation prevalence was 0% between 0-25 years, 9% between 26-30 years and 6% between 31-35 years. In conclusion, BRCA testing is recommended in TNBC patients diagnosed ≤60 years, regardless of family cancer history or histotype, and by using immunohistochemical staining <10% for both ER and/PR. In luminal-like early-onset BC, a lower BRCA detection rate was observed, suggesting a role for other predisposing genes along with BRCA genetic testing.

15.
BMC Cancer ; 20(1): 418, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404154

RESUMO

BACKGROUND: Elderly patients are underrepresented in clinical study where combined endocrine strategies were compared to endocrine therapy (ET) in hormone receptors positive, HER2 negative, metastatic breast cancer. The role of the new endocrine approaches in elderly women is still unclear. METHODS: We performed a meta-analysis of first line phase II/III randomized trials on ET versus combined strategies considering clinical benefit and safety profile. Trials with hazard ratio (HR) for PFS in elderly patients were included. RESULTS: Overall, the meta-analysis showed a PFS advantage for the experimental arms [HR 0.77, p 0.016] with a significant high/moderate heterogeneity [I2 65.46%, p 0.005]. For patients on CDK 4/6 inhibitors and ET, HR was 0.57 (p < 0.0001), with low heterogeneity [I2 0.0001%, p 0.96]. Hematological adverse events, as well as diarrhea with Abemaciclib, were significantly higher in elderly population. CONCLUSIONS: The magnitude of PFS benefit due to the combined strategies in elderly patients is similar to those reported in the overall clinical trial population. Adding CDK4/6 inhibitors to ET significantly prolongs PFS, even if toxicity profile have to be carefully considered. Future trials should be designed taking into account patients' age, geriatric assessment and comorbidity.

16.
Fam Cancer ; 19(4): 291-295, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32328861

RESUMO

Some hereditary ovarian cancer cases can be associated with a mutation of a gene involved in the DNA double-strand break repair system other than BRCA, such as BRIP1. This mutation is an emerging indication for prophylactic risk-reducing salpingo-oophorectomy (RRSO): however, anomalous tubal pathologic lesions have not yet been reported during RRSO performed for this specific indication (BRIP1), as largely reported for BRCA mutation carriers. An asymptomatic 64-year-old woman with a family history of ovarian and breast cancer agreed to undergo RRSO for a pathogenic variant of the BRIP1 gene (heterozygous NM_032043.2: c.124delT, p. Cys42Valfs) with normal BRCA genes. Histological examination showed the presence of high-grade serous carcinoma of the fimbria of the right tube of a maximum diameter of 0.4 cm (final FIGO stage IIB). The pathogenic mechanism that leads to the development of high-grade serous ovarian/fallopian tube cancer in patients with mutations of BRIP1 should be the same as for patients with mutations of BRCA1 and 2. Our case confirms to consider BRIP1 mutation to be sufficient to justify RRSO at 45-50 years old.

17.
Eur J Neurosci ; 52(8): 3963-3978, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32282965

RESUMO

Investigating the neurobiology of language impairment and treatment in chronic stroke aphasia using fMRI requires an understanding of measurement variability within and between participants. In this multicenter study, we evaluated the scan-rescan reliability of an auditory and visual (written) story comprehension paradigm in stroke participants with aphasia (N = 65) and healthy controls (N = 22). The multi-modal task was conducted twice (~1 week apart) on separate visits upon study enrolment and twice again at completion three months later. A non-language visuomotor task was studied in the aphasia group only, which was conducted once per time point (3 months apart). While participants were asked to make responses during the comprehension task, these in-scanner responses were not recorded. Reliability was assessed using intraclass correlation coefficient (ICC) at both group and individual participant levels. The visual story comprehension condition had higher reliability than the auditory condition in both groups, with participants with aphasia exhibiting lower reliability than controls in both conditions (stroke ICC = .43, healthy ICC = .81). Differences in reliability within the group of participants with aphasia were found to be partially explained by overall language impairment as well as greater head motion. In the participants with aphasia, the visuomotor paradigm was found to have greater reliability than the story comprehension task at equivalent interscan intervals (visuomotor = 0.50, comprehension = 0.34), and its reliability was not associated with language impairment. This work highlights the importance of considering the reliability of fMRI tasks in aphasia research, provides strategies to improve reliability and has potential implications for the field of clinical neuroimaging in general.

18.
J Int Soc Sports Nutr ; 17(1): 6, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31959202

RESUMO

BACKGROUND: Sports nutritional supplements containing branched-chain amino acids (BCAA) have been widely reported to improve psychological and biological aspects connected to central fatigue and performance in endurance exercise, although the topic is still open to debate. The aim of the present study was to determine whether the intake of a commercially available BCAA-based supplement, taken according to the manufacturer's recommendations, could affect the rating of perceived exertion (RPE) and performance indexes at the beginning (1d) and end of a 9-week (9w) scheduled high intensity interval training program, with an experimental approach integrating the determination of psychometric, performance, metabolic and blood biochemical parameters. METHODS: This was a randomized double-blind placebo-controlled study. Thirty-two untrained, healthy young adults (20 males and 12 female) were enrolled. A high-intensity endurance cycling (HIEC) test was used to induce fatigue in the participants: HIEC consisted in ten 90 s sprints interspersed by ten 3 min recovery phases and followed by a final step time to exhaustion was used. In parallel with RPE, haematological values (creatine kinase, alanine, BCAA, tryptophan, ammonia and glucose levels), and performance indexes (maximal oxygen consumption - VO2max, power associated with lactate thresholds - WLT1, WLT2 and time to exhaustion - TTE) were assessed. All subject took the supplement (13.2 g of carbohydrates; 3.2 g of BCAA and 1.6 g of L-alanine per dose) or placebo before each test and training session. Dietary habits and training load were monitored during the entire training period. RESULTS: The administration of the supplement (SU) at 1d reduced RPE by 9% during the recovery phase, as compared to the placebo (PL); at 9w the RPE scores were reduced by 13 and 21% during the sprint and recovery phase, respectively; at 9w, prolonged supplement intake also improved TTE and TRIMP. SU intake invariably promoted a rapid increase (within 1 h) of BCAA serum blood levels and prevented the post-HIEC tryptophan: BCAA ratio increase found in the PL group, at both 1d and 9w. There was no difference in dietary habits between groups and those habits did not change over time; no difference in glycemia was found between SU and PL. VO2max, WLT1 and WLT2 values improved over time, but were unaffected by supplement intake. CONCLUSIONS: On the whole, these results suggest that i) the intake of the BCAA-based commercially available supplement used in this study reduces RPE as a likely consequence of an improvement in the serum tryptophan: BCAA ratio; ii) over time, reduced RPE allows subjects to sustain higher workloads, leading to increased TRIMP and TTE.


Assuntos
Alanina/farmacologia , Aminoácidos de Cadeia Ramificada/farmacologia , Desempenho Atlético , Carboidratos/farmacologia , Suplementos Nutricionais , Substâncias para Melhoria do Desempenho/farmacologia , Método Duplo-Cego , Teste de Esforço , Feminino , Treinamento Intervalado de Alta Intensidade , Humanos , Masculino , Esforço Físico , Adulto Jovem
19.
Neuroscience ; 439: 153-162, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047977

RESUMO

Erythropoietin (EPO) is a hematopoietic growth factor that has an important role in the erythropoiesis. EPO and its receptor (EPO-R) are expressed all over in the mammalian brain. Furthermore, it has been reported that EPO may exert neuroprotective effect in animal models of brain disorders as ischemia and epilepsy. Here, we investigate whether EPO could modulate the GABA-evoked currents (IGABA) in both human epileptic and non-epileptic control brain tissues. Therefore, we transplanted in Xenopus oocytes cell membranes obtained from autoptic and surgical brain tissues (cortex) of seven temporal lope epilepsy (TLE) patients and of five control patients. Two microelectrodes voltage-clamp technique has been used to record IGABA. Moreover, qRT-PCR assay was performed in the same human tissues to quantify the relative gene expression levels of EPO/EPO-R. To further confirm experiments in oocytes, we performed additional experiments using patch-clamp recording in slices obtained from rat cerebellum. We show that exposure to EPO significantly increased the amplitude of the IGABA in all the patients analyzed. No differences in the expression of EPO and EPO-R in both TLE and control patients have been found. Notably, the increase of IGABA has been recorded also in rat cerebellar slices. Our findings show a new modulatory action of EPO on GABAA receptors (GABAA-Rs). This effect could be relevant to balance the GABAergic dysfunction in human TLE. This article is part of a Special Issue entitled: Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries.

20.
Nutrients ; 12(1)2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31861755

RESUMO

The adult gut microbiota contains trillions of microorganisms of thousands of different species. Only one third of gut microbiota are common to most people; the rest are specific and contribute to enhancing genetic variation. Gut microorganisms significantly affect host nutrition, metabolic function, immune system, and redox levels, and may be modulated by several environmental conditions, including physical activity and exercise. Microbiota also act like an endocrine organ and is sensitive to the homeostatic and physiological changes associated with training; in turn, exercise has been demonstrated to increase microbiota diversity, consequently improving the metabolic profile and immunological responses. On the other side, adaptation to exercise might be influenced by the individual gut microbiota that regulates the energetic balance and participates to the control of inflammatory, redox, and hydration status. Intense endurance exercise causes physiological and biochemical demands, and requires adequate measures to counteract oxidative stress, intestinal permeability, electrolyte imbalance, glycogen depletion, frequent upper respiratory tract infections, systemic inflammation and immune responses. Microbiota could be an important tool to improve overall general health, performance, and energy availability while controlling inflammation and redox levels in endurance athletes. The relationship among gut microbiota, general health, training adaptation and performance, along with a focus on sport supplements which are known to exert some influence on the microbiota, will be discussed.


Assuntos
Desempenho Atlético/fisiologia , Suplementos Nutricionais , Exercício Físico/fisiologia , Microbioma Gastrointestinal/fisiologia , Aminoácidos , Animais , Humanos , Camundongos , Micronutrientes , Probióticos , Ratos , Estresse Fisiológico/fisiologia
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