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1.
Biochemistry ; 63(1): 42-52, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38146842

RESUMO

Inositol phosphates and their pyrophosphorylated derivatives are responsive to the phosphate supply and are agents of phosphate homeostasis and other aspects of physiology. It seems likely that the enzymes that interconvert these signals work against the prevailing milieu of mixed populations of competing substrates and products. The synthesis of inositol pyrophosphates is mediated in plants by two classes of ATP-grasp fold kinase: PPIP5 kinases, known as VIH, and members of the inositol tris/tetrakisphosphate kinase (ITPK) family, specifically ITPK1/2. A molecular explanation of the contribution of ITPK1/2 to inositol pyrophosphate synthesis and turnover in plants is incomplete: the absence of nucleotide in published crystal structures limits the explanation of phosphotransfer reactions, and little is known of the affinity of potential substrates and competitors for ITPK1. Herein, we describe a complex of ADP and StITPK1 at 2.26 Å resolution and use a simple fluorescence polarization approach to compare the affinity of binding of diverse inositol phosphates, inositol pyrophosphates, and analogues. By simple HPLC, we reveal the novel catalytic capability of ITPK1 for different inositol pyrophosphates and show Ins(3,4,5,6)P4 to be a potent inhibitor of the inositol pyrophosphate-synthesizing activity of ITPK1. We further describe the exquisite specificity of ITPK1 for the myo-isomer among naturally occurring inositol hexakisphosphates.


Assuntos
Difosfatos , Solanum tuberosum , Fosfatos de Inositol , Ácido Fítico
2.
J Sex Med ; 21(7): 614-619, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38628064

RESUMO

BACKGROUND: Female orgasmic disorder is listed in the DSM-5 and is defined as the persistent or recurrent inability to have an orgasm. Many depressed women may experience sexual dysfunction, including female orgasmic disorder. AIM: The study sought to analyze the relationship between depressive disorders and attention-deficit/hyperactivity disorder (ADHD) and their influence on the development of female orgasmic disorder. METHODS: A total of 221 Dominican women participated in this case-control study. The case group consisted of 107 women diagnosed with female orgasmic disorder, while the control group consisted of 114 women without any sexual dysfunction. OUTCOMES: The diagnosis of ADHD was obtained from the participants' medical records, previously conducted using the DSM-5-TR criteria. The Beck Depression Inventory II was used to assess the severity of depressive symptoms in both groups. RESULTS: There was a significant relationship between female orgasmic disorder and ADHD and depression. The results of multiple logistic regression indicated that the highest risk of female orgasmic disorder was observed in women with ADHD (odds ratio [OR], 4.91; 95% confidence interval [CI], 2.46-9.20; P < .001), women with severe depression (OR, 2.50; 95% CI, 1.08-6.96; P = .04), and women who had sexual intercourse that focused on penetration (OR, 2.02; 95% CI, 1.03-3.98; P = .04). CLINICAL IMPLICATIONS: These findings may have important implications for the prevention and treatment of sexual disorders in women. STRENGTHS AND LIMITATIONS: This design selected all diagnosed cases of female orgasmic disorder and did not select a specific subgroup. However, some limitations must be considered. This study was conducted in a single clinic, although it should be noted that it is the main clinic for the treatment of sexual dysfunction in the country. A further limitation could be that this type of study design does not allow for statements about causality to be made. CONCLUSION: There is an increased risk of female orgasmic disorder in women with ADHD, with severe depression, and who engage in penetrative sex.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Depressão , Disfunções Sexuais Psicogênicas , Humanos , Feminino , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Adulto , Estudos de Casos e Controles , Disfunções Sexuais Psicogênicas/epidemiologia , Disfunções Sexuais Psicogênicas/psicologia , Depressão/epidemiologia , República Dominicana , Adulto Jovem , Orgasmo , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica
3.
Pediatr Blood Cancer ; 71(8): e31120, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38825724

RESUMO

The EPICO (Spanish general registry of COVID-19 in children)-SEHOP (Spanish Society of Pediatric Hematology and Oncology) platform gathers data from children with SARS-CoV-2 in Spain, allowing comparison between children with cancer or allogeneic hematopoietic stem cell transplantation (alloHSCT) and those without. The infection is milder in the cancer/alloHSCT group than in children without comorbidities (7.1% vs. 14.7%), except in children with recent alloHSCT (less than 300 days), of which 35.7% experienced severe COVID-19. These data have been shared with the SEHOP members to support treatment and isolation policies akin to those for children without cancer, except for those with recent alloHSCT or additional comorbidities. This highlights the collaborative registries potential in managing pandemic emergencies.


Assuntos
COVID-19 , Comorbidade , Transplante de Células-Tronco Hematopoéticas , Neoplasias , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/complicações , Criança , Masculino , Adolescente , Feminino , Pré-Escolar , Fatores de Risco , Neoplasias/epidemiologia , Neoplasias/terapia , Lactente , Espanha/epidemiologia , Sistema de Registros , Transplante Homólogo
4.
Phys Chem Chem Phys ; 26(3): 2519-2528, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38170811

RESUMO

Clathrate hydrates have the ability to encapsulate atoms and molecules within their cavities, and thus they could be potentially large storage capacity materials. The present work studies the multiple cage occupancy effects in the recently discovered He@sII crystal. On the basis of previous theoretical and experimental findings, the stability of He(1/1)@sII, He(1/4)@sII and He(2/4)@sII crystals was analysed in terms of structural, mechanical and energetic properties. For this purpose, first-principles DFT/DFT-D computations were performed by using both semi-local and non-local functionals, not only to elucidate which configuration is the most energetically favoured, but also to scrutinize the relevance of the long-range dispersion interactions in these kinds of compounds. We have encountered that dispersion interactions play a fundamental role in describing the underlying interactions, and different tendencies were observed depending on the choice of the functional. We found that PW86PBE-XDM shows the best performance, while the non-local functionals tested here were not able to correctly account for them. The present results reveal that the most stable configuration is the one presenting singly occupied D cages and tetrahedrally occupied H cages (He(1/4)@sII) in line with the experimental observation.

5.
Arch Sex Behav ; 53(2): 735-744, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37875628

RESUMO

In the last few years, the frequency of sexually transmitted infections (STI) has increased, as has the number of people with multiple infections. The aim of our study was to describe the epidemiological characteristics of persons with repeated bacterial STI and to determine the risk factors for these episodes in persons living in Barcelona during the period 2007-2018. We studied all cases of bacterial STI included in the STI registry of Barcelona. Repeated STI were defined as a diagnosis of gonorrhea, syphilis, or lymphogranuloma venereum (LGV) after a first episode of one of these infections. Analysis was stratified by sex and place of birth. The factors associated with time to reinfection were determined by Kaplan-Meier estimates, while the factors associated with risk of infection were determined by a Cox proportional hazards model. Of 9927 persons with a diagnosis of bacterial STI, 1690 (17.0%) had at least two episodes of STI during the study period. On multivariate analysis, repeat STI were independently associated with male sex assigned at birth (HR: 3.45; 95%CI 2.22-5.36), age less than 34 years (HR: 1.22; 95%CI 1.10-1.35); gay, bisexual, and other men who have sex with men, and transgender o transsexual woman (GBSMS/Trans) (HR: 4.03; 95%CI 3.24-5.03), having gonorrhea as first diagnosis (HR:1.49, 95%CI 1.34-1.66) or LGV (HR:1.75; 95%CI 1.47-2.08) and coinfection with HIV (HR:1.98; 95%CI 1.78-2.21). Sexual health programs should be strengthened to prevent STI and reinfection in key populations.


Assuntos
Gonorreia , Infecções por HIV , Linfogranuloma Venéreo , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Sífilis , Feminino , Recém-Nascido , Masculino , Humanos , Adulto , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Homossexualidade Masculina , Infecções por HIV/diagnóstico , Espanha/epidemiologia , Reinfecção , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologia
6.
Pediatr Dermatol ; 41(5): 927-928, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38456245

RESUMO

Two siblings presented with straw-colored, frizzy, and wiry hair. They had no associated abnormalities and no family history of abnormal hair. Trichoscopy showed the longitudinal groove in the hair shafts, characteristic of uncombable hair syndrome. Molecular genetic analysis revealed a new pathogenic variant (c.1374dup; p. Val459ArgfsTer15) in PADI3, not previously described.


Assuntos
Doenças do Cabelo , Irmãos , Humanos , Doenças do Cabelo/genética , Doenças do Cabelo/diagnóstico , Doenças do Cabelo/patologia , Feminino , Masculino , Cabelo/anormalidades , Cabelo/patologia , Criança , Pré-Escolar
7.
J Med Internet Res ; 26: e54934, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684088

RESUMO

BACKGROUND: Falls and their consequences are a serious public health problem worldwide. Each year, 37.3 million falls requiring medical attention occur. Therefore, the analysis of fall risk is of great importance for prevention. Artificial intelligence (AI) represents an innovative tool for creating predictive statistical models of fall risk through data analysis. OBJECTIVE: The aim of this review was to analyze the available evidence on the applications of AI in the analysis of data related to postural control and fall risk. METHODS: A literature search was conducted in 6 databases with the following inclusion criteria: the articles had to be published within the last 5 years (from 2018 to 2024), they had to apply some method of AI, AI analyses had to be applied to data from samples consisting of humans, and the analyzed sample had to consist of individuals with independent walking with or without the assistance of external orthopedic devices. RESULTS: We obtained a total of 3858 articles, of which 22 were finally selected. Data extraction for subsequent analysis varied in the different studies: 82% (18/22) of them extracted data through tests or functional assessments, and the remaining 18% (4/22) of them extracted through existing medical records. Different AI techniques were used throughout the articles. All the research included in the review obtained accuracy values of >70% in the predictive models obtained through AI. CONCLUSIONS: The use of AI proves to be a valuable tool for creating predictive models of fall risk. The use of this tool could have a significant socioeconomic impact as it enables the development of low-cost predictive models with a high level of accuracy. TRIAL REGISTRATION: PROSPERO CRD42023443277; https://tinyurl.com/4sb72ssv.


Assuntos
Acidentes por Quedas , Inteligência Artificial , Acidentes por Quedas/prevenção & controle , Humanos , Medição de Risco/métodos , Equilíbrio Postural
8.
J Vis ; 24(5): 6, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38727688

RESUMO

Prior research has demonstrated high levels of color constancy in real-world scenarios featuring single light sources, extensive fields of view, and prolonged adaptation periods. However, exploring the specific cues humans rely on becomes challenging, if not unfeasible, with actual objects and lighting conditions. To circumvent these obstacles, we employed virtual reality technology to craft immersive, realistic settings that can be manipulated in real time. We designed forest and office scenes illuminated by five colors. Participants selected a test object most resembling a previously shown achromatic reference. To study color constancy mechanisms, we modified scenes to neutralize three contributors: local surround (placing a uniform-colored leaf under test objects), maximum flux (keeping the brightest object constant), and spatial mean (maintaining a neutral average light reflectance), employing two methods for the latter: changing object reflectances or introducing new elements. We found that color constancy was high in conditions with all cues present, aligning with past research. However, removing individual cues led to varied impacts on constancy. Local surrounds significantly reduced performance, especially under green illumination, showing strong interaction between greenish light and rose-colored contexts. In contrast, the maximum flux mechanism barely affected performance, challenging assumptions used in white balancing algorithms. The spatial mean experiment showed disparate effects: Adding objects slightly impacted performance, while changing reflectances nearly eliminated constancy, suggesting human color constancy relies more on scene interpretation than pixel-based calculations.


Assuntos
Percepção de Cores , Sinais (Psicologia) , Iluminação , Estimulação Luminosa , Realidade Virtual , Humanos , Percepção de Cores/fisiologia , Iluminação/métodos , Adulto , Masculino , Feminino , Estimulação Luminosa/métodos , Adulto Jovem
9.
Sensors (Basel) ; 24(9)2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38733034

RESUMO

INTRODUCTION: The choice of materials for covering plantar orthoses or wearable insoles is often based on their hardness, breathability, and moisture absorption capacity, although more due to professional preference than clear scientific criteria. An analysis of the thermal response to the use of these materials would provide information about their behavior; hence, the objective of this study was to assess the temperature of three lining materials with different characteristics. MATERIALS AND METHODS: The temperature of three materials for covering plantar orthoses was analyzed in a sample of 36 subjects (15 men and 21 women, aged 24.6 ± 8.2 years, mass 67.1 ± 13.6 kg, and height 1.7 ± 0.09 m). Temperature was measured before and after 3 h of use in clinical activities, using a polyethylene foam copolymer (PE), ethylene vinyl acetate (EVA), and PE-EVA copolymer foam insole with the use of a FLIR E60BX thermal camera. RESULTS: In the PE copolymer (material 1), temperature increases between 1.07 and 1.85 °C were found after activity, with these differences being statistically significant in all regions of interest (p < 0.001), except for the first toe (0.36 °C, p = 0.170). In the EVA foam (material 2) and the expansive foam of the PE-EVA copolymer (material 3), the temperatures were also significantly higher in all analyzed areas (p < 0.001), ranging between 1.49 and 2.73 °C for EVA and 0.58 and 2.16 °C for PE-EVA. The PE copolymer experienced lower overall overheating, and the area of the fifth metatarsal head underwent the greatest temperature increase, regardless of the material analyzed. CONCLUSIONS: PE foam lining materials, with lower density or an open-cell structure, would be preferred for controlling temperature rise in the lining/footbed interface and providing better thermal comfort for users. The area of the first toe was found to be the least overheated, while the fifth metatarsal head increased the most in temperature. This should be considered in the design of new wearables to avoid excessive temperatures due to the lining materials.


Assuntos
Órtoses do Pé , Temperatura , Humanos , Feminino , Masculino , Adulto , Adulto Jovem , Polivinil/química , Polietileno/química , Polímeros/química , Teste de Materiais
10.
Molecules ; 29(19)2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39407512

RESUMO

The acrylation degree of vegetable oils plays a relevant role in determining the mechanical properties of the resulting polymers. Both epoxide and acrylate functionalities participate in polymerization reactions, producing various types of chemical bonds in the polymer network, which contribute to specific properties such as molecular size distribution, crosslinking degree, and glass transition temperature (Tg). The accurate identification of epoxide and acrylated groups in triglyceride molecules helps to predict their behavior during the polymerization process. A methodology based on analytical spectrometric techniques, such as direct infusion, mass spectrometry with electrospray ionization, and ultra-high-performance liquid chromatography, is used in combination with FTIR and 1H NMR to characterize the epoxy and acrylic functionalities in the fatty chains with different numbers of carbon atoms of partially acrylated triglycerides obtained by a non-catalytic reaction.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38855926

RESUMO

This study evaluated the efficacy of a multi-protease on the performance, egg quality and digestibility of laying hen. The study had four treatments: Control (without multi-protease, CON), Pro 1.2 (CON + 0.1% multi-protease), Pro 2.4 (CON + 0.2% multi-protease) and Pro 3.6 (CON + 0.3% multi-protease). Each treatment was replicated six times (replicate = experimental unit = one pen with 15 hens) to give a total of 360 layer hens of the Hy-line breed. The study lasted for a total of 3 months (14 day adaptation period + 84 days experimental period). The effects of the additive were assessed on: the performance variables, egg quality and ileal amino acid (AA) digestibility. At the end of the study, dietary supplementation with Pro 2.4 and Pro 3.6 improved (p < 0.05) hen-day egg production, egg mass and eggshell thickness compared with CON at the peak phase. Further improvements (p < 0.05) were observed in the digestibility of crude protein and AAs such as isoleucine, lysine, threonine and cysteine at Pro 2.4 and Pro 3.6 protease supplementation levels compared with CON, while arginine and alanine were higher (p < 0.05) at Pro 3.6 compared with CON. No differences were reported for other performances such as body weight, average daily feed intake, average egg weight, feed conversion ratio, eggshell hardness and all the egg qualities measured. Overall, the results from this study showed better efficacy at Pro 2.4 and Pro 3.6 on the performance of laying hen during the peak phase.

12.
Gastroenterol Hepatol ; : 502226, 2024 Jun 29.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38950646

RESUMO

OBJECTIVE: Direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV) infection offer an opportunity to eliminate the disease. This study aimed to identify and relink to care HCV patients previously lost to medical follow-up in the health area of Pontevedra and O Salnés (Spain) using an artificial intelligence-assisted system. PATIENTS AND METHODS: Active retrospective search of previously diagnosed HCV cases recorded in the Galician Health Service proprietary health information exchange database using the Herramientas para la EXplotación de la INformación (HEXIN) application. RESULTS AND CONCLUSIONS: Out of 99 lost patients identified, 64 (64.6%) were retrieved. Of these, 62 (96.88%) initiated DAA treatment and 54 patients (87.1%) achieved a sustained virological response. Mean time from HCV diagnosis was over 10 years. Main reasons for loss to follow-up were fear of possible adverse effects of treatment (30%) and mobility impediments (21%). Among the retrieved patients, almost one in three presented advanced liver fibrosis (F3) or cirrhosis (F4) at evaluation. In sum, HCV patients lost to follow-up can be retrieved by screening past laboratory records. This strategy promotes the achievement of HCV elimination goals.

13.
Phys Chem Chem Phys ; 25(25): 16844-16855, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37314248

RESUMO

One of the several possibilities offered by the interesting clathrate hydrates is the opportunity to encapsulate several atoms or molecules, in such a way that more efficient storage materials could be explored or new molecules that otherwise do not exist could be created. These types of applications are receiving growing attention from technologists and chemists, given the future positive implications that they entail. In this context, we investigated the multiple cage occupancy of helium clathrate hydrates, to establish stable novel hydrate structures or ones similar to those predicted previously by experimental and theoretical studies. To this purpose, we analyzed the feasibility of including an increased number of He atoms inside the small (D) and large (H) cages of the sII structure through first-principles properly assessed density functional approaches. On the one hand, we have computed energetic and structural properties, in which we examined the guest-host and guest-guest interactions in both individual and two-adjacent clathrate-like sII cages by means of binding and evaporation energies. On the other hand, we have carried out a thermodynamical analysis on the stability of such He-containing hydrostructures in terms of changes in enthalpy, ΔH, Gibbs free energy, ΔG, and entropy, ΔS, during their formation process at various temperature and pressure values. In this way, we have been able to make a comparison with experiments, reaffirming the ability of computational DFT approaches to describe such weak guest-host interactions. In principle, the most stable structure involves the encapsulation of one and four He atoms inside the D and H sII cages, respectively; however, more He atoms could be entrapped under lower temperature and/or higher pressure thermodynamic conditions. We foresee such accurate computational quantum chemistry approaches contributing to the current emerging machine-learning model development.

14.
BMC Womens Health ; 23(1): 387, 2023 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-37482613

RESUMO

BACKGROUND: Dyspareunia is defined as the occurrence of pain during or after sexual intercourse, which directly affects physical, sexual, and mental health. This condition can lead to depression, anxiety, and low self-esteem in women who experience it. OBJECTIVES: The aim of this research was to evaluate the effectiveness of physical therapy interventions for the treatment of female dyspareunia. DESIGN: A systematic review and meta-analysis was conducted. METHOD: Search of publications was conducted in Scopus, Medline, Pubmed, Cinahl and Web of Science. Treatment effects were defined as standardized mean difference and their 95% confidence intervals. Statistical heterogeneity was assessed using Crohan's Q test and quantified using the I2 index. RESULTS: Of the 19 articles selected, six applied multimodal physiotherapy treatments; five, electrotherapy; three, Thiele's massage; two, interdisciplinary interventions or pelvic floor muscle training; and one, extracorporeal shockwave therapy. The meta-analysis showed significant results for the variables pain and quality of life with the interventions based on electrotherapy and electrotherapy combined with pelvic floor muscle training. These interventions did not show significant results for the improvement of sexual function. CONCLUSIONS: Physiotherapy techniques are effective and procedures have been identified with reliable results in improving pain and quality of life in patients with dyspareunia. One of the most important aspects is the strengthening of the perineal musculature and the application of Transcutaneous Electrical Nerve Stimulation. Furthermore, manual trigger point release therapy and Thiele massage, optimize and guarantee the reduction of pain intensity. PROSPERO REGISTRATION: CRD42021236155.


Assuntos
Dispareunia , Estimulação Elétrica Nervosa Transcutânea , Humanos , Feminino , Dispareunia/terapia , Qualidade de Vida , Modalidades de Fisioterapia , Dor
15.
Clin Rehabil ; 37(6): 747-759, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36583575

RESUMO

OBJECTIVE: To evaluate the efficacy of percutaneous electrolysis for the treatment of patients with tendinopathies. DATA SOURCES: A systematic search of publications was conducted in Pubmed, Cinahl, Medline, Scopus and Web of Science. METHODS: The Oxford 2011 Levels of Evidence and the Jadad scale were used to assess the quality of studies. The mean and standard deviation were obtained for each study group and used to calculate the effect size. The DerSimonian and Laird method was used to develop a random-effects model. RESULTS: Of the 14 articles, four applied percutaneous electrolysis to the knee, three to the shoulder, three to the elbow, two to the hip and two to the ankle and foot. A meta-analysis on intensity of pain (evaluated with algometer and the Visual Analogue Scale) was performed on studies comparing percutaneous electrolysis with a control group, indicating that the groups treated with percutaneous electrolysis had better results (p = 0.01). Although percutaneous electrolysis did not overcome the analgesic effect achieved by corticosteroid injections. CONCLUSIONS: The percutaneous electrolysis is effective for the treatment of tendinopathies. The combination of this technique with eccentric training has proven to be one of the most effective treatments to date for improving pain. PROSPERO Registration: CRD42021230005.


Assuntos
Terapia por Exercício , Tendinopatia , Humanos , Terapia por Exercício/métodos , Resultado do Tratamento , Tendinopatia/terapia , Dor , Eletrólise/métodos
16.
Soc Networks ; 73: 80-88, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36628334

RESUMO

University students have changed their behaviour due to the COVID-19 pandemic. In this paper, we describe the characteristics of PCR+ and PCR- nodes, analyse the structure, and relate the structure of student leaders to pandemic contagion as determined by PCR+ in 93 residential university students. Leadership comes from the male students of social science degrees who have PCR +, with an eigenvector centrality structure, ß-centrality, and who are part of the bow-tie structure. There was a significant difference in ß-centrality between leaders and non-leaders and in ß-centrality between PCR+ and non-leaders. Leading nodes were part of the bow-tie structure. MR-QAP results show how residence and scientific branch were the most important factors in network formation. Therefore, university leaders should consider influential leaders, as they are vectors for disseminating both positive and negative outcomes.

17.
Proc Natl Acad Sci U S A ; 117(28): 16456-16464, 2020 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-32616572

RESUMO

Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene leading to the presence of premature termination codons (PTC). Previous transcriptional studies have shown reduced DMD transcript levels in DMD patient and animal model muscles when PTC are present. Nonsense-mediated decay (NMD) has been suggested to be responsible for the observed reduction, but there is no experimental evidence supporting this claim. In this study, we aimed to investigate the mechanism responsible for the drop in DMD expression levels in the presence of PTC. We observed that the inhibition of NMD does not normalize DMD gene expression in DMD. Additionally, in situ hybridization showed that DMD messenger RNA primarily localizes in the nuclear compartment, confirming that a cytoplasmic mechanism like NMD indeed cannot be responsible for the observed reduction. Sequencing of nascent RNA to explore DMD transcription dynamics revealed a lower rate of DMD transcription in patient-derived myotubes compared to healthy controls, suggesting a transcriptional mechanism involved in reduced DMD transcript levels. Chromatin immunoprecipitation in muscle showed increased levels of the repressive histone mark H3K9me3 in mdx mice compared to wild-type mice, indicating a chromatin conformation less prone to transcription in mdx mice. In line with this finding, treatment with the histone deacetylase inhibitor givinostat caused a significant increase in DMD transcript expression in mdx mice. Overall, our findings show that transcription dynamics across the DMD locus are affected by the presence of PTC, hinting at a possible epigenetic mechanism responsible for this process.


Assuntos
Códon sem Sentido/genética , Distrofina/genética , Distrofia Muscular de Duchenne/genética , RNA Mensageiro/genética , Animais , Códon sem Sentido/metabolismo , Modelos Animais de Doenças , Distrofina/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos mdx , Distrofia Muscular de Duchenne/metabolismo , Degradação do RNAm Mediada por Códon sem Sentido , RNA Mensageiro/metabolismo
18.
J Neuroeng Rehabil ; 20(1): 165, 2023 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-38082316

RESUMO

BACKGROUND: Strokes may cause some swallowing difficulty or associated dysphagia in 25-80% of patients. This phenomenon has been linked to increased morbidity and mortality. Therefore, the aim of this study was to evaluate the efficacy of transcranial direct current stimulation in patients with dysphagia in post-stroke patients. METHODS: A systematic search in PubMed, Scopus, Web of Science and MEDLINE was conducted. The articles must have to evaluate an intervention that included transcranial direct current stimulation; the sample had to consist exclusively of patients with post-stroke dysphagia; and the experimental design consisted of randomized controlled trial. Difference in mean differences and their 95% confidence interval were calculated as the between-group difference in means divided by the pooled standard deviation. The I2 statistic was used to determine the degree of heterogeneity. RESULTS: Of the 9 investigations analyzed, all applied transcranial direct current stimulation in combination with conventional dysphagia therapy to the experimental group. All the studies analyzed identified improvements in swallowing function and meta-analysis confirmed their strong effect on reducing the risk of penetration and aspiration (Hedges's g = 0.55). The results showed that participants who received transcranial direct current stimulation significantly improved swallowing function. CONCLUSIONS: Transcranial direct current stimulation has positive effects in the treatment of poststroke dysphagia by improving swallowing function, oral and pharyngeal phase times and the risk of penetration and aspiration. Furthermore, its combination with conventional dysphagia therapy, balloon dilatation with catheter or training of the swallowing muscles ensures improvement of swallowing function. PROSPERO registration ID CRD42022314949.


Assuntos
Transtornos de Deglutição , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Humanos , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Estimulação Transcraniana por Corrente Contínua/métodos , Acidente Vascular Cerebral/complicações , Deglutição , Reabilitação do Acidente Vascular Cerebral/métodos , Resultado do Tratamento
19.
J Clin Ultrasound ; 51(2): 300-310, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36785499

RESUMO

The widespread incorporation of first-trimester scanning between 11 and 13 weeks' gestation has shifted from the screening of chromosomal abnormalities, mainly by measuring nuchal translucency thickness and visualization of the nasal bone, to a more detailed study of the fetal anatomy leading to early detection of several structural congenital anomalies. This goal can be improved by the routine and focused sonographic assessment of specific anatomic planes and the identification of distinctive landmarks that can help disclosing a particular, non-evident condition. In this article we present the basis for a basic, early examination of the fetal brain during screening using a four-step technique, which can be readily incorporated during the first-trimester scan. The technique includes the focused visualization of the cranial contour, choroid plexuses of the lateral ventricles and midline, aqueduct of Sylvius, brainstem, fourth ventricle, and the choroid plexus of the fourth ventricle. The rationale for this approach is presented and discussed.


Assuntos
Medição da Translucência Nucal , Ultrassonografia Pré-Natal , Gravidez , Feminino , Humanos , Ultrassonografia Pré-Natal/métodos , Idade Gestacional , Primeiro Trimestre da Gravidez , Medição da Translucência Nucal/métodos , Encéfalo/diagnóstico por imagem
20.
J Clin Ultrasound ; 51(5): 827-832, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37128687

RESUMO

The sonographic findings in four fetuses presenting with ventriculomegaly at first-trimester ultrasound that were subsequently diagnosed as having agenesis of the corpus callosum (ACC) are described. The diagnosis of early ventriculomegaly was suspected subjectively by identification of increased cerebrospinal fluid within the lateral ventricles and confirmed by measuring choroid plexus-to-lateral ventricle length and area ratios. Subsequent scans revealed complete ACC in two cases and partial ACC in the other two. This report adds to the increasing evidence suggesting that first-trimester ventriculomegaly is a strong sonographic marker of underlying brain anomalies, including less evident malformations such as ACC. Detailed second-trimester fetal neurosonography in those women continuing their pregnancies should be performed.


Assuntos
Hidrocefalia , Diagnóstico Pré-Natal , Gravidez , Feminino , Humanos , Primeiro Trimestre da Gravidez , Corpo Caloso/diagnóstico por imagem , Ultrassonografia Pré-Natal , Hidrocefalia/diagnóstico por imagem , Feto , Imageamento por Ressonância Magnética , Estudos Retrospectivos
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