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51.
Maria L. Dentici Vittorio Maglione Emanuele Agolini Gino Catena Rossella Capolino Valentina Lanari Antonio Novelli Lorenzo Sinibaldi Davide Vecchio Michaela V. Gonfiantini Marina Macchiaiolo Maria C. Digilio Bruno Dallapiccola Andrea Bartuli 《American journal of medical genetics. Part A》2020,182(8):1977-1984
The tubulinopathies refer to a wide range of brain malformations caused by mutations in one of the seven genes encoding different tubulin's isotypes. The β‐tubulin isotype III (TUBB3) gene has a primary function in nervous system development and axon generation and maintenance, due to its neuron‐specific expression pattern. A recurrent heterozygous mutation, c.1228G > A; p.E410K, in TUBB3 gene is responsible of a rare disorder clinically characterized by congenital fibrosis of the extraocular muscle type 3 (CFEOM3), intellectual disability and a wide range of neurological and endocrine abnormalities. Other mutations have been described spanning the entire gene and genotype–phenotype correlations have been proposed. We report on a 3‐year‐old boy in whom clinical exome sequencing allowed to identify a de novo TUBB3 E410K mutation as the molecular cause underlying a complex phenotype characterized by a severe bilateral palpebral ptosis refractory to eye surgery, psychomotor delay, absent speech, hypogonadism, celiac disease, and cyclic vomiting. Brain MRI revealed thinning of the corpus callosum with no evidence of malformation cortical dysplasia. We reviewed available records of patients with TUBB3 E410K mutation and compared their phenotype with the clinical outcome of patients with other mutations in TUBB3 gene. The present study confirms that TUBB3 E410K results in a clinically recognizable phenotype, unassociated to the distinct cortical dysplasia caused by other mutations in the same gene. Early molecular characterization of TUBB3 E410K syndrome is critical for targeted genetic counseling and prompt prospective care in term of neurological, ophthalmological, endocrine, and gastrointestinal follow‐up. 相似文献
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Jürgen Schüttler Donald R. Stanski Paul F. White Anthony J. Trevor Yukio Horai Davide Verotta Lewis B. Sheiner 《Journal of pharmacokinetics and pharmacodynamics》1987,15(3):241-253
The pharmacodynamics of a racemic mixture of ketamine R,S (±)-ketamine and of each enantiomer, S(+)-ketamine and R(–)-ketamine, were studied in five volunteers. The median frequency of the electroencephalogram (EEG) power spectrum, a continuous noninvasive measure of the degree of central nervous system (CNS) depression (pharmacodynamics), was related to measured serum concentrations of drug (pharmacokinetics). The concentration-effect relationship was described by an inhibitory sigmoid Emax pharmacodynamic model, yielding estimates of both maximal effect (Emax) and sensitivity (IC50) to the racemic and enantiomeric forms of ketamine. R(–)-ketamine was not as effective as R,S(±)-ketamine or S(+)-ketamine in causing EEG slowing. The maximal decrease (mean±SD) of the median frequency (Emax)for R(–)-ketamine was 4.4±0.5 Hz and was significantly different fromR,S (±)-ketamine (7.6 ±1.7 Hz) and S(+)-ketamine (8.3±1.9Hz). The ketamine serum concentration that caused one-half of the maximal median frequency decrease (IC50) was 1.8±0.5g/mL for R(–)-ketamine; 2.0±0.5 g/mL for R,S(±)-ketamine; and 0.8±0.4 g/mL for S(+)-ketamine. Because the maximal effect (Emax) of the R(–)-ketamine was different from that of S(+)-ketamine and R,S(±)-ketamine, it was not possible to directly compare the potency (i.e., IC50) of these compounds. Accordingly, a classical agonist/partial-agonist interaction model was examined, using the separate enantiomer results to predict racemate results. Although the model did not predict racemate results well, its failure was not so great as to provide clear evidence of synergism (or excess antagonism) of the enantiomers.This work was supported in part by a Starter Grant from the American Society of Anesthesiologists, the Biomedical Research Support Grant NIH 2S07RR5353-20, 1981, (P.F.W.); and NIH and NIA Research Grants NS-17956 and AG03104 (D.R.S., A.J.T., L.B.S). The research fellowship of Dr. Schüttler was made possible by a NATO Foundation Grant (300-402-511-3), awarded by the German Academic Exchange Service. This study is part of Dr. Schüttler's Habilitation Thesis for the Faculty of Medicine at the University of Bonn, West Germany. Dr. Verotta is a fellow of the program of advanced training established by EEC and Regione Lombardia on leave of absence from Mario Negri Institute of Pharmacological Research, Milan, Italy. 相似文献
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55.
Davide Serrano Chiara Pozzi Silvia Guglietta Bruno Fosso Mariano Suppa Patrizia Gnagnarella Federica Corso Federica Bellerba Debora Macis Valentina Aristarco Paolo Manghi Nicola Segata Cristina Trovato Maria Giulia Zampino Marinella Marzano Bernardo Bonanni Maria Rescigno Sara Gandini 《Nutrients》2021,13(2)
Obesity and diet are associated with colorectal cancer (CRC) risk, and microbiome could mediate this risk factor. To investigate this interaction, we performed a case–control study (34 CRC cases and 32 controls) and analyzed fecal microbiota composition using 16S rRNA metabarcoding and sub-sequential shotgun analyses of genomic bacterial DNA to evaluate the role of microbiome and diet in CRC etiology, taking into account vitamin D and other risk biomarkers. Dietary habits were evaluated using a short questionnaire. Multivariate methods for data integration and mediation analysis models were used to investigate causal relationships. CRC cases were significantly more often deficient in vitamin D than controls (p = 0.04); FokI and CYP24A1 polymorphism frequency were different between cases and controls (p = 0.03 and p = 0.02, respectively). A diet poor in fatty fish and rich in carbohydrates was found to be significantly associated with CRC risk (p = 0.011). The mediation analysis confirmed the significant role of the microbiome in mediating CRC risk—increasing levels of Bifidobacteria/Escherichia genera ratio, an indicator of “healthy” intestinal microbiome, can overcome the effect of diet on CRC risk (p = 0.03). This study suggests that microbiome mediates the diet effect on CRC risk, and that vitamin D, markers of inflammation, and adipokines are other factors to consider in order to achieve a better knowledge of the whole carcinogenic process. 相似文献
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57.
Vincenzo Di Stefano Raffaele Ornello Andrea Gagliardo Angelo Torrente Elisa Illuminato Valeria Caponnetto Ilaria Frattale Raffaella Golini Chiara Di Felice Fabiola Graziano Maria Caccamo Davide Ventimiglia Salvatore Iacono Gabriella Matarazzo Francesco Armetta Giuseppe Battaglia Alberto Firenze Simona Sacco Filippo Brighina 《Nutrients》2021,13(4)
Background: The restrictions taken to control the rapid spread of COVID-19 resulted in a sudden, unprecedented change in people’s lifestyle, leading to negative consequences on general health. This study aimed to estimate the impact of such changes on migraine severity during 2020 March–May lockdown. Methods: Patients affected by migraine with or without aura, diagnosed by expert physicians, completed a detailed interview comprehensive of: assessment of migraine characteristics; measure of physical activity (PA) levels; measure of the intake frequency of main Italian foods; the Insomnia Severity Index (ISI) questionnaire investigating sleep disorders. Results: We included 261 patients with a mean age of 44.5 ± 12.3 years. During social distancing, 72 patients (28%) reported a headache worsening, 86 (33%) an improvement, and 103 (39%) a stable headache frequency. A significant decrease of the PA levels during COVID-19 quarantine in the whole study sample was observed (median total metabolic equivalent task (METs) decreased from 1170 to 510; p < 0.001). Additionally, a significant difference was reported on median ISI scores (from 7 to 8; p < 0.001), which were increased in patients who presented a stable or worsening headache. Conclusions: Our study confirmed that the restrictions taken during the pandemic have affected the practice of PA levels and sleep quality in migraine. Hence, PA and sleep quality should be assessed to find strategies for an improvement in quality of life. 相似文献
58.
Silvio Buscemi Carola Buscemi Davide Corleo Giovanni De Pergola Rosalia Caldarella Francesco Meli Cristiana Randazzo Salvatore Milazzo Anna Maria Barile Giuseppe Rosafio Valentina Settipani Sabina Gurrera Antonio Maria Borzì Marcello Ciaccio 《Nutrients》2021,13(6)
Background: Vitamin D plays a pivotal role in calcium and phosphorus metabolism, also influencing bone tissue. Several studies have reported that vitamin D blood levels were significantly lower in people with obesity, probably due to its uptake by the adipose tissue. Clinical studies that investigated the changes of circulating levels of vitamin D following weight loss reported controversial data. A very low-calorie ketogenic diet is acknowledged as a reliable treatment to achieve a rapid weight loss. Therefore, we investigated the effect of weight loss, consequent to a very low-calorie ketogenic diet, on vitamin D blood concentrations. Methods: A cohort of 31 people with obesity underwent a very low-calorie ketogenic diet for 10–12 weeks. The serum concentrations of vitamin D, parathormone, calcium and phosphorous were measured before and after weight loss; they were compared to a control group of 20 non-obese, non-diabetic, age- and gender-matched persons. Results: Patients with obesity had a higher habitual intake of vitamin D than the control group (p < 0.05). However, the vitamin D blood levels of the obese group were significantly lower than those of the control group (p < 0.005) and they increased after weight loss (p < 0.001). At baseline, vitamin D blood concentrations of the persons with obesity were significantly correlated with both fat mass–kg (r = −0.40; p < 0.05) and body mass index (r = −0.47; p < 0.01). Following very low-calorie ketogenic diet, the change in vitamin D serum concentrations was correlated only with the change in fat mass–kg (r = −0.43; p < 0.01). Conclusion: This study confirmed that patients with obesity have lower vitamin D levels that normalize after significant weight loss, supporting the hypothesis that vitamin D is stored in the adipose tissue and released following weight loss. 相似文献
59.
Cannizzaro Delia Tropeano Maria Pia Milani Davide Spaggiari Riccardo Zaed Ismail Mancarella Cristina Lasio Giovanni Battista Fornari Maurizio Servadei Franco Cardia Andrea 《Neurosurgical review》2021,44(3):1217-1225
Neurosurgical Review - Chordoma is a rare slow-growing neoplastic bone lesion. However, they show an invasive local growth and high recurrence rate, leading to an overall survival rate of 65% at 5... 相似文献
60.
Belotti Francesco Tengattini Francesco Mattavelli Davide Ferrari Marco Fiorentino Antonio Agnelli Silvia Schreiber Alberto Nicolai Piero Fontanella Marco Maria Doglietto Francesco 《Neurosurgical review》2021,44(1):279-287
Neurosurgical Review - Recently, endoscopic transsphenoidal transclival approaches have been developed and their role is widely accepted for extradural pathologies. Their application to intradural... 相似文献