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Cancer is a global health problem, and supramolecular chemotherapy is emerging as a novel strategy to battle the disease. Here, we first evaluated the thermodynamic and kinetic stability of the complexes formed between several water-soluble per-substituted pillar[5]arene derivatives and capecitabine (1), a widely used oral chemotherapeutic prodrug. The exchange rate was studied, for the first time in pillararene chemistry, by the 19 F guest exchange saturation transfer (GEST) NMR technique. Importantly, when we evaluated the effect of complexation on the characteristics of 1, we found that the complexation of 1 with such pillar[5]arene hosts increased capecitabine stability at acidic pH very significantly and slowed its enzymatic degradation by the carboxylesterase enzyme in a manner that depended on the host. These interesting findings could have implications on the clinical use of this heavily used prodrug and might affect the management of cancer patients.
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Profármacos , Humanos , Profármacos/química , Capecitabina , Compuestos de Amonio Cuaternario/química , Concentración de Iones de HidrógenoRESUMEN
BACKGROUND AND AIMS: Women with primary ovarian insufficiency exhibit an unfavorable cardiovascular risk profile. A common cause for primary ovarian insufficiency is fragile X premutation (FXPC), and data on the cardiovascular risk factors in women with FXPC are scarce. We aimed to assess the prevalences of abnormal metabolic components among FXPC. METHODS AND RESULTS: Clinical, anthropometric and laboratory data were collected from 71 women with FXPC and compared to 78 women referred for counseling in an in-vitro fertilization clinic (control group). The mean ± SD ages of the FXPC and control groups were 33.5 ± 5.6 and 36.2 ± 5.3 years, respectively (p = 0.003). In a logistic regression analysis, the FXPC group had increased risks for hyperglycemia, hypertriglyceridemia, central obesity and low high-density lipoprotein cholesterol, of 21.8-fold (95% CI 2.7-175, p = 0.004), 6.9-fold (95% CI 2.5-18.7, p < 0.0001), 3.1-fold (95% CI 1.4-6.9, p = 0.005) and 2.4-fold (95% CI 1.1-5.2, p = 0.03), compared to the control group. The FXPC group had 2.7-fold higher prevalence of two abnormal metabolic components; 19% met the full criteria of MetS, compared to 3% of the control group. Neither CGG repeats nor ovarian reserve markers were associated with metabolic risk. CONCLUSIONS: Carriers of fragile X premutation are at increased metabolic risk from early adulthood; waist circumference, glucose and lipid levels are particularly elevated. We recommend metabolic screening for all women with FMR1 premutation, to enable early interventions for prevention of long-term cardiovascular comorbidities.
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Síndrome del Cromosoma X Frágil , Síndrome Metabólico , Insuficiencia Ovárica Primaria , Adulto , Femenino , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/diagnóstico , Síndrome del Cromosoma X Frágil/epidemiología , Síndrome del Cromosoma X Frágil/genética , Humanos , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Síndrome Metabólico/genética , Mutación , Insuficiencia Ovárica Primaria/diagnóstico , Insuficiencia Ovárica Primaria/epidemiología , Insuficiencia Ovárica Primaria/genéticaRESUMEN
Secondary formamides are widely encountered in biology and exist as mixtures of both cis and trans isomers. Here, we assess hydrophilicity differences between isomeric formamides through direct competition experiments. Formamides bearing long aliphatic chains were sequestered in a water-soluble molecular container having a hydrophobic cavity with an end open to the aqueous medium. NMR spectroscopic experiments reveal a modest preference (<1 kcal/mol) for aqueous solvation of the trans formamide terminals over the cis isomers. With diformamides, the supramolecular approach allows staging of intramolecular competition between short-lived species with subtle differences in hydrophobic properties.
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PURPOSE: To evaluate whether ethnicity affects the risk of full mutation expansion among females heterozygous for FMR1 premutation. METHODS: Women who carry the FMR1 premutation alelle of Jewish origin who underwent fragile X prenatal diagnosis between 2011 and 2018 in two medical centers in Israel were included. The heterozygote women and fetuses were analyzed for the number of CGG repeats and AGG interruptions. RESULTS: Seven hundred sixty-six subjects were included. Parental ethnicity was fully concordant in 592 cases (Jewish, Ashkenazi, and non-Ashkenazi). Ashkenazi compared with non-Ashkenazi heterozygotes have a significantly higher mean number of CGG repeats (68 ± 8.7, 64 ± 6.4 respectively, P = 0.03) and a lower mean number of AGG interruptions (0.89 ± 0.83, 1.60 ± 1.18 respectively, p = 0.0001). Overall, 56/198 (28.2%) fetuses of Ashkenazi heterozygotes had an expansion to a full mutation compared with 6/98 among the non-Ashkenazi (6.1%) (p = 0.001). Multivariate analysis demonstrated that, in addition to CGG repeats and AGG interruptions (which contributed 68.3% of variance), ethnicity is an independent risk factor for a full mutation expansion (odds ratio [OR] = 2.04, p < 0.001) and accounted for 9% of the variation of a full mutation expansion. CONCLUSION: Apart from significant differences regarding the number of CGG repeats and AGG interruptions between Ashkenazi and non-Ashkenazi heterozygotes, ethnicity independently affects the risk of a full mutation.
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Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil , Síndrome del Cromosoma X Frágil , Alelos , Femenino , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Síndrome del Cromosoma X Frágil/diagnóstico , Síndrome del Cromosoma X Frágil/genética , Heterocigoto , Humanos , Israel/epidemiología , Mutación , Expansión de Repetición de Trinucleótido/genéticaRESUMEN
Correction for 'QSAR without borders' by Eugene N. Muratov et al., Chem. Soc. Rev., 2020, DOI: 10.1039/d0cs00098a.
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Prediction of chemical bioactivity and physical properties has been one of the most important applications of statistical and more recently, machine learning and artificial intelligence methods in chemical sciences. This field of research, broadly known as quantitative structure-activity relationships (QSAR) modeling, has developed many important algorithms and has found a broad range of applications in physical organic and medicinal chemistry in the past 55+ years. This Perspective summarizes recent technological advances in QSAR modeling but it also highlights the applicability of algorithms, modeling methods, and validation practices developed in QSAR to a wide range of research areas outside of traditional QSAR boundaries including synthesis planning, nanotechnology, materials science, biomaterials, and clinical informatics. As modern research methods generate rapidly increasing amounts of data, the knowledge of robust data-driven modelling methods professed within the QSAR field can become essential for scientists working both within and outside of chemical research. We hope that this contribution highlighting the generalizable components of QSAR modeling will serve to address this challenge.
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Química Farmacéutica/métodos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/metabolismo , Preparaciones Farmacéuticas/química , Algoritmos , Animales , Inteligencia Artificial , Bases de Datos Factuales , Diseño de Fármacos , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Modelos Moleculares , Relación Estructura-Actividad Cuantitativa , Teoría Cuántica , Reproducibilidad de los ResultadosRESUMEN
Supramolecular systems in water are of paramount importance and those based on hydrogen bonds are both intriguing and scarce. Here, after studying the peculiar host-guest complexes formed between per-dimethylamino-pillar[5]arene (1) and the bis-sulfonates 2 a-c, we describe the formation of the first hydrogen-bond-based supramolecular pentagonal boxes (SPBs), which are stable in water. These pH-responsive SPBs are constructed from 1 as a body, benzene polycarboxylic acids 3 a,b as lid compounds, and 2 a-c as guests. We demonstrate that encapsulation of 2 a-c in pillar[5]arene 1 and in the highly stable water-soluble SPBs, that is, 1(3 a)2 and 1(3 b)2 , is both temperature and pH dependent and, quite interestingly, depends, on the nature of the lid compounds used for capping the boxes even at high pH. We also highlight the difference in the 1 Hâ NMR characteristics of 2 b and 2 c in the cavity of 1 and the SPBs.
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A deep cavitand binds long-chain trans,trans- and trans,cis-bis-formamide isomers in water solution giving a pair of caviplexes in a ca. 60:40 ratio. Both caviplexes display in/out guest exchange dynamics that are slow on the 1 Hâ NMR chemical shift timescale, but fast on the EXSY timescale. We apply diffusion-ordered NMR spectroscopy (DOSY) to characterize the caviplexes. On the diffusion timescale, the guest in/out exchange processes feature intermediate dynamics allowing the assessment of their kinetic stabilities. We found that the trans,cis-bis-formamide isomers form kinetically more stable caviplexes than the trans,trans-counterparts. We also show that the kinetic stabilities of the bis-formamide caviplexes relate well with their relative thermodynamic stabilities. Fortunately, the tuning of the DOSY parameters allowed the observation of the exchange dynamics as slow processes on the experiment timescale.
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A web-based resource for meta-analysis of nanomaterials toxicity is developed whereby the utility of Bayesian networks (BNs) is illustrated for exploring the cellular toxicity of Cd-containing quantum dots (QDs). BN models are developed based on a dataset compiled from 517 publications comprising 3028 cell viability data samples and 837 IC50 values. BN QD toxicity (BN-QDTox) models are developed using both continuous (i.e., numerical) and categorical attributes. Using these models, the most relevant attributes identified for correlating IC50 are: QD diameter, exposure time, surface ligand, shell, assay type, surface modification, and surface charge, with the addition of QD concentration for the cell viability analysis. Data exploration via BN models further enables identification of possible association rules for QDs cellular toxicity. The BN models as web-based applications can be used for rapid intelligent query of the available body of evidence for a given nanomaterial and can be readily updated as the body of knowledge expands.
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Células/efectos de los fármacos , Puntos Cuánticos/toxicidad , Pruebas de Toxicidad , Teorema de Bayes , Supervivencia Celular/efectos de los fármacos , Concentración 50 InhibidoraRESUMEN
Mapping average axon diameter (AAD) and axon diameter distribution (ADD) in neuronal tissues non-invasively is a challenging task that may have a tremendous effect on our understanding of the normal and diseased central nervous system (CNS). Water diffusion is used to probe microstructure in neuronal tissues, however, the different water populations and barriers that are present in these tissues turn this into a complex task. Therefore, it is not surprising that recently we have witnessed a burst in the development of new approaches and models that attempt to obtain, non-invasively, detailed microstructural information in the CNS. In this work, we aim at challenging and comparing the microstructural information obtained from single diffusion encoding (SDE) with double diffusion encoding (DDE) MRI. We first applied SDE and DDE MR spectroscopy (MRS) on microcapillary phantoms and then applied SDE and DDE MRI on an ex vivo porcine spinal cord (SC), using similar experimental conditions. The obtained diffusion MRI data were fitted by the same theoretical model, assuming that the signal in every voxel can be approximated as the superposition of a Gaussian-diffusing component and a series of restricted components having infinite cylindrical geometries. The diffusion MRI results were then compared with histological findings. We found a good agreement between the fittings and the experimental data in white matter (WM) voxels of the SC in both diffusion MRI methods. The microstructural information and apparent AADs extracted from SDE MRI were found to be similar or somewhat larger than those extracted from DDE MRI especially when the diffusion time was set to 40 ms. The apparent ADDs extracted from SDE and DDE MRI show reasonable agreement but somewhat weaker correspondence was observed between the diffusion MRI results and histology. The apparent subtle differences between the microstructural information obtained from SDE and DDE MRI are briefly discussed.
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Axones/fisiología , Imagen de Difusión por Resonancia Magnética , Médula Espinal/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Animales , Filamentos Intermedios/metabolismo , Fantasmas de Imagen , PorcinosRESUMEN
Macrocyclic host structures for generating transiently bound 129 Xe have been used in various ultra-sensitive NMR and MRI applications for molecular sensing of biochemical analytes. They are based on hyperpolarized nuclei chemical exchange saturation transfer (Hyper-CEST). Here, we tested a set of water-soluble pillar[5]arenes with different counterions in order to compare their potential contrast agent abilities with that of cryptophane-A (CrA), the most widely used host for such purposes. The exchange of Xe with such compounds was found to be sensitive to the type of ions present in solution and can be used for switchable magnetization transfer (MT) contrast that arises from off-resonant pre-saturation. We demonstrate that the adjustable MT magnitude depends on the interplay of saturation parameters and found that the optimum MT contrast surpasses the CrA CEST performance at moderate saturation power. Since modification of such water-soluble pillar[5]arenes is straightforward, these compounds can be considered a promising platform for designing various sensors that may complement the field of Xe HyperCEST-based biosensing MRI.
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Calixarenos/química , Espectroscopía de Resonancia Magnética/métodos , Isótopos de Xenón/química , Compuestos Policíclicos/química , Solubilidad , Agua/químicaRESUMEN
We aim to retrospectively evaluate the role of increasing the gonadotropin daily dose from 450 IU/day to 300 IU twice a day on IVF-ET outcome in poor responder patients. All consecutive women admitted to our IVF unit and underwent COH consisting of daily gonadotropin dose of 450 IU, followed by an IVF cycle using 300 IU twice a day, were included. Ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and pregnancy rate was assessed. Twenty-three patients undergoing both cycles were evaluated. While there was no between-group difference in the duration of COH, number of 2PN embryos, fertilization rate and number of embryos transferred, patients receiving daily gonadotropin 300 IU twice a day achieved a significantly higher peak estradiol levels (3350.39 ± 2364.26 vs. 2223.74 ± 1299.91; p < .03, respectively), and yielded significantly higher number of follicles >15 mm in diameter on day of hCG administration (3.2 ± 2.4 vs 1.8 ± 1; p < .03, respectively) and higher number of oocytes retrieved (3.48 ± 2.54 vs 1.87 ± 1.1; p < .02, respectively) with an acceptable live birth rate (5%). To conclude, in poor responders undergoing COH a daily gonadotropin dose of 450 IU, increasing the dose to 300 IU twice daily may result in higher oocyte yield, with the possible improvement in IVF outcome.
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Fármacos para la Fertilidad Femenina/administración & dosificación , Fertilización In Vitro/métodos , Hormona Folículo Estimulante/administración & dosificación , Hormona Luteinizante/administración & dosificación , Menotropinas/administración & dosificación , Inducción de la Ovulación/métodos , Adulto , Tasa de Natalidad , Esquema de Medicación , Combinación de Medicamentos , Femenino , Humanos , Recuperación del Oocito , Embarazo , Índice de Embarazo , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The feasibility of wellhead water treatment in small communities for nitrate removal and salinity reduction via a flexible high recovery RO system was evaluated through analysis of treatment options, laboratory and onsite field tests. In small remote communities that rely on septic systems for residential wastewater treatment, discharge of the RO residual stream (containing nitrate) to the community septic tank is shown to be a feasible option. It is demonstrated that RO treatment with a system that employs partial concentrate recycle, integrated with a pressure intensifier, enabled the use of a relatively low-pressure feed pump while allowing high recovery operation. The approach of integrating RO treatment into existing community small water systems is demonstrated to be suitable for providing effective nitrate removal and salinity reduction over wide range of nitrate and salinity levels, while meeting community water demand and regulatory water quality requirements.
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Salinidad , Purificación del Agua , Estudios de Factibilidad , Ósmosis , Eliminación de Residuos Líquidos , Aguas ResidualesRESUMEN
We describe the preparation of the first water-soluble pH-responsive supramolecular hexagonal boxes (SHBs) based on multiple charge-assisted hydrogen bonds between peramino-pillar[6]arenes 2 with the molecular "lid" mellitic acid (1 a). The interaction between 2 and 1 a, as well as the other "lids" pyromellitic and trimesic acids (1 b and 1 c, respecively) were studied by a combination of experimental and computational methods. Interestingly, the addition of 1 a to the complexes of the protonated form of pillar[6]arene 2, that is, 3, with bis-sulfonate 4 a or 4 b, immediately led to guest escape along with the formation of closed 1 a2 2 supramolecular boxes. Moreover, the process of the openning and closing of the supramolecular boxes along with threading and escaping of the guests, respectively, was found to be reversible and pH-responsive. This study paves the way for the easy and modular preparation of different SHBs that may have myriad applications.
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Rationally designed two-component supramolecular organogels based on multiple chemical interactions between percarboxylato- and peramino-pillararenes are described. Mixing low concentration solutions (<1 % w/v) of decacarboxylato-pillar[5]areneâ (1) with decaamino-pillar[5]arenesâ (2 b-d) affords, rapidly and without heating, organogels displaying an exceptional combination of properties. These supramolecular organogels, the characteristics of which are tunable, were found to be thixotropic and thermally stable, with Tgel values in some cases exceeding the boiling point of the embedded solvent. It is demonstrated that both structural complementarity and multivalency are important determinants in the gelation process of these attractive soft materials.
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Calmodulin lysine methyl transferase (CaM KMT) is ubiquitously expressed and highly conserved from plants to vertebrates. CaM is frequently trimethylated at Lys-115, however, the role of CaM methylation in vertebrates has not been studied. CaM KMT was found to be homozygously deleted in the 2P21 deletion syndrome that includes 4 genes. These patients present with cystinuria, severe intellectual disabilities, hypotonia, mitochondrial disease and facial dysmorphism. Two siblings with deletion of three of the genes included in the 2P21 deletion syndrome presented with cystinuria, hypotonia, a mild/moderate mental retardation and a respiratory chain complex IV deficiency. To be able to attribute the functional significance of the methylation of CaM in the mouse and the contribution of CaM KMT to the clinical presentation of the 2p21deletion patients, we produced a mouse model lacking only CaM KMT with deletion borders as in the human 2p21deletion syndrome. No compensatory activity for CaM methylation was found. Impairment of complexes I and IV, and less significantly III, of the mitochondrial respiratory chain was more pronounced in the brain than in muscle. CaM KMT is essential for normal body growth and somatosensory development, as well as for the proper functioning of the adult mouse brain. Developmental delay was demonstrated for somatosensory function and for complex behavior, which involved both basal motor function and motivation. The mutant mice also had deficits in motor learning, complex coordination and learning of aversive stimuli. The mouse model contributes to the evaluation of the role of methylated CaM. CaM methylation appears to have a role in growth, muscle strength, somatosensory development and brain function. The current study has clinical implications for human patients. Patients presenting slow growth and muscle weakness that could result from a mitochondrial impairment and mental retardation should be considered for sequence analysis of the CaM KMT gene.
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Metiltransferasas/fisiología , Animales , Encéfalo/enzimología , Encéfalo/fisiopatología , Deleción Cromosómica , Retroalimentación Sensorial , Femenino , Masculino , Metilación , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados , Fuerza Muscular , Músculo Esquelético/enzimología , Músculo Esquelético/patología , Procesamiento Proteico-PostraduccionalRESUMEN
PURPOSE: To detect which factors influence decision-making among pregnant FMR1 premutation carriers regarding the preferred mode of genetic diagnosis: IVF-PGT-M (in vitro fertilization with preimplantation genetic testing for monogenic gene diseases), or CVS (chorionic villus sampling), or AC (amniocentesis) after spontaneous conception. METHODS: In Israel FMR1 premutation preconception genetic screening is offered, free of charge, to every woman in her reproductive years. FMR1 premutation carriers with ≥ 70 CGG repeats, or a history of FXS offspring, are offered IVF-PGT-M. This is a historical cohort study including all pregnant FMR1 premutation carriers who underwent prenatal diagnosis between the years 2011 and 2016 at a tertiary medical center. Data were collected from electronic charts and through phone interviews. RESULTS: One hundred seventy-five women with high-risk pregnancies who were offered IVF-PGT-M were evaluated. In 37 pregnancies (21%), the women decided to undergo IVF-PGT-M. Using the generalized estimating equations (GEE) statistical method including seven parameters, we found that previous termination of pregnancy due to FXS and advanced woman's age were significantly associated with making the decision to undergo IVF-PGT-M. Previously failed IVF was the most significant parameter in a woman's decision not to undergo IVF-PGT-M. CONCLUSION: The most dominant factor affecting the decision of FMR1 premutation carriers to choose spontaneous conception with prenatal diagnosis versus IVF-PGT-M is a previous experience of failed IVF treatments. Women whose IVF treatments failed in the past tended to try to conceive naturally and later, during the course of the pregnancy, perform CVS or AC. Conversely, women who previously experienced a termination of pregnancy (TOP) due to an affected fetus, and older women, preferred to undergo IVF-PGT-M procedures.
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Toma de Decisiones , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Pruebas Genéticas/métodos , Mutación , Diagnóstico Preimplantación/métodos , Diagnóstico Prenatal/métodos , Técnicas Reproductivas Asistidas/tendencias , Adulto , Estudios de Cohortes , Femenino , Síndrome del Cromosoma X Frágil/diagnóstico , Síndrome del Cromosoma X Frágil/genética , Heterocigoto , Humanos , EmbarazoRESUMEN
INTRODUCTION: Fragile X Syndrome (FXS), the most common form of inherited mental retardation, is caused by a trinucleotide repeat expansion (CGG) in the 5'-untranslated region of the Fragile X Mental Retardation 1 (FMR1) gene located at Xq27.3. Patients with fragile X -related mental retardation, carry the full mutation CGG-repeat expansions (>200 CGG repeats), which are generally accompanied by hypermethylation of the promoter region, with the consequent transcriptional silencing of the FMR1 gene and absence of the encoded FMR1 protein (FMRP). Expansion of the CGG triplet number above the normal range (n=5-54) towards the so-called premutation status (n=55-199) is associated with increased risk for Fragile X-Associated Premature Ovarian Insufficiency (FXPOI) in females and Fragile X-Associated Tremor/ Ataxia Syndrome (FXTAS) predominantly in males. In addition, premutation women carriers are at increased risk for learning disabilities, as well as psychologic, endocrine, autoimmune and metabolic disorders. The observation that premutation carriers, both males and females, have increased FMR1 transcript levels, led researchers to suggest a similar molecular pathogenesis in both FXPOI and FXTAS. Two models have been proposed as the culprits of FXTAS and FXPOI: The toxic RNA gain-of-function model and the Repeat Associated Non-AUG initiated (RAN) translation protein toxicity model. The Fragile X Multidisciplinary Center in Sheba Medical Center, at Tel Hashomer includes a team of geneticists, fertility specialists, endocrinologists, psychologists and neurologists who work together in order to provide early detection of FMR1 premutation carriers and offer FMR1 premutation carriers and their families adequate multidisciplinary medical consultation, follow-up and care.
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Ataxia/genética , Síndrome del Cromosoma X Frágil/genética , Insuficiencia Ovárica Primaria/genética , Temblor/genética , Expansión de Repetición de Trinucleótido/genética , Portador Sano , Femenino , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/genética , Humanos , Masculino , MutaciónRESUMEN
INTRODUCTION: At the end of the last century Fragile X syndrome was identified, and the main syndrome characteristics were discovered. The syndrome is caused from a flaw in the number of nucleotide repeats that encodes for a regulatory protein which is critical for neural connectivity and normal brain development. The syndrome is characterized by neurodevelopmental and intellectual disabilities, autism spectrum features and other clinical features associated with the same gene aberration. The number of trinucleotide repeats have a direct effect on the outcome and the need for genetic counseling. We advocate performing genetic tests for every child with developmental delay, learning disabilities, autism spectrum disorders and especially, intellectual impairment. It is also advisable to check the number of nucleotide repeats of the gene, in every woman suffering from infertility or early menopause. In addition, genetic testing should be performed on older adults manifesting early symptoms of Parkinson's disease, balance instability, tremor or cognitive dysfunction with unknown etiology. Due to the tremendous progress in understanding the biological mechanisms of the syndrome, new molecules/drugs have been proposed and are tested, in order to find a way to bypass the defect mechanism underlying the disorder. We will review the most commonly used drugs in the treatment of Fragile X syndrome and many medications that are currently under investigation as a more targeted treatment.
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Trastorno del Espectro Autista , Síndrome del Cromosoma X Frágil , Pruebas Genéticas , Medicina de Precisión , Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/genética , Niño , Femenino , Síndrome del Cromosoma X Frágil/tratamiento farmacológico , Síndrome del Cromosoma X Frágil/genética , Humanos , Infertilidad Femenina , Menopausia Prematura , Temblor , Repeticiones de TrinucleótidosRESUMEN
Diffusion MRI is extensively used to study brain microarchitecture and pathologies, and water diffusion appears highly anisotropic in the white matter (WM) of the spinal cord (SC). Despite these facts, the use of diffusion MRI to study the SC, which has increased in recent years, is much less common than that in the brain. In the present review, after a brief outline of early studies of diffusion MRI (DWI) and diffusion tensor MRI (DTI) of the SC, we provide a short survey on DTI and on diffusion MRI methods beyond the tensor that have been used to study SC microstructure and pathologies. After introducing the porous view of WM and describing the q-space approach and q-space diffusion MRI (QSI), we describe other methodologies that can be applied to study the SC. Selected applications of the use of DTI, QSI, and other more advanced diffusion MRI methods to study SC microstructure and pathologies are presented, with some emphasis on the use of less conventional diffusion methodologies. Because of length constraints, we concentrate on structural studies and on a few selected pathologies. Examples of the use of diffusion MRI to study dysmyelination, demyelination as in experimental autoimmune encephalomyelitis and multiple sclerosis, amyotrophic lateral sclerosis, and traumatic SC injury are presented. We conclude with a brief summary and a discussion of challenges and future directions for diffusion MRI of the SC. Copyright © 2016 John Wiley & Sons, Ltd.