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1.
Disabil Rehabil ; : 1-9, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38975724

RESUMEN

PURPOSE: Research suggests that rates for autism may be higher in cerebral palsy than in the general population. For those with severe bilateral physical impairment (GMFCS level IV and V) and little or no speech, describing a profile of social communication skills has been difficult because there are currently no assessments for early social communication specifically tailored for these children. Our aim was to explore the assessment of aspects of joint attention and social reciprocity in this group of children with CP. METHODS: We compared the performance of children with bilateral CP on carefully designed assessments of joint attention and social responsiveness with groups of children with Down syndrome and autism. All three groups were matched for chronological age and mental age. RESULTS: Approximately 30% of the children with bilateral CP had early social communication scores similar to the autistic children. The remaining 70% of children with CP had a range of early social communication scores similar to the children with Down syndrome. CONCLUSION: It is possible to assess key early social communication skills in non-speaking children with bilateral motor disability. This could provide insights to help clinicians and caregivers as they discuss abilities and explore potential areas for intervention.


With carefully designed activities, which do not rely on motor skills or verbal exchanges, it was possible to assess joint attention and social responsiveness skills in a group of non-speaking children with bilateral motor disability.We were able to identify a subgroup of non-speaking children with severe motor disability (approximately 30% of our cohort) whose scores on our assessments were similar to a group of autistic children.The ability to describe key early social communication skills should provide insights to help clinicians and caregivers as they discuss abilities and explore potential areas for intervention.

2.
J Med Chem ; 67(15): 12945-12968, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39018526

RESUMEN

Acute respiratory viral infections, such as pneumovirus and respiratory picornavirus infections, exacerbate disease in COPD and asthma patients. A research program targeting respiratory syncytial virus (RSV) led to the discovery of GS-7682 (1), a novel phosphoramidate prodrug of a 4'-CN-4-aza-7,9-dideazaadenosine C-nucleoside GS-646089 (2) with broad antiviral activity against RSV (EC50 = 3-46 nM), human metapneumovirus (EC50 = 210 nM), human rhinovirus (EC50 = 54-61 nM), and enterovirus (EC50 = 83-90 nM). Prodrug optimization for cellular potency and lung cell metabolism identified 5'-methyl [(S)-hydroxy(phenoxy)phosphoryl]-l-alaninate in combination with 2',3'-diisobutyrate promoieties as being optimal for high levels of intracellular triphosphate formation in vitro and in vivo. 1 demonstrated significant reductions of viral loads in the lower respiratory tract of RSV-infected African green monkeys when administered once daily via intratracheal nebulized aerosol. Together, these findings support additional evaluation of 1 and its analogues as potential therapeutics for pneumo- and picornaviruses.


Asunto(s)
Antivirales , Picornaviridae , Profármacos , Infecciones por Virus Sincitial Respiratorio , Animales , Antivirales/farmacología , Antivirales/química , Profármacos/farmacología , Profármacos/química , Profármacos/síntesis química , Chlorocebus aethiops , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/virología , Humanos , Picornaviridae/efectos de los fármacos , Relación Estructura-Actividad , Virus Sincitiales Respiratorios/efectos de los fármacos , Descubrimiento de Drogas , Nucleósidos/química , Nucleósidos/farmacología , Infecciones por Picornaviridae/tratamiento farmacológico , Infecciones por Picornaviridae/virología
3.
Nat Commun ; 15(1): 5154, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886378

RESUMEN

Cancer incidence escalates exponentially with advancing age; however, the underlying mechanism remains unclear. In this study, we build a chronological molecular clock at single-cell transcription level with a mammary stem cell-enriched population to depict physiological aging dynamics in female mice. We find that the mammary aging process is asynchronous and progressive, initiated by an early senescence program, succeeded by an entropic late senescence program with elevated cancer associated pathways, vulnerable to cancer predisposition. The transition towards senescence program is governed by a stem cell factor Bcl11b, loss of which accelerates mammary ageing with enhanced DMBA-induced tumor formation. We have identified a drug TPCA-1 that can rejuvenate mammary cells and significantly reduce aging-related cancer incidence. Our findings establish a molecular portrait of progressive mammary cell aging and elucidate the transcriptional regulatory network bridging mammary aging and cancer predisposition, which has potential implications for the management of cancer prevalence in the aged.


Asunto(s)
Envejecimiento , Neoplasias de la Mama , Senescencia Celular , Femenino , Animales , Ratones , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/genética , Humanos , Glándulas Mamarias Animales/patología , Glándulas Mamarias Animales/metabolismo , Células Madre/metabolismo
4.
Augment Altern Commun ; : 1-8, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38775646

RESUMEN

The relationships between the use of nouns and verbs, and other word classes have been well established in the typical language development literature. However, questions remain as to whether the same relationships are seen in the language use of individuals who use graphic symbol-based augmentative and alternative communication (AAC). The aim of the study was to examine relationships between the use of verbs and nouns, and the use of prepositions, adverbs, and adjectives through a secondary analysis of language transcripts taken from 12 children and adolescents who used aided AAC in conversation with an adult. A series of multiple linear mixed-effect regression analyses showed a positive predictive association between the use of verbs and the use of prepositions and adverbs, as well as a positive predictive relationship between the use of nouns and the use of adjectives. The theoretical and practical implications of these findings are discussed.

5.
Dis Aquat Organ ; 158: 143-155, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38813855

RESUMEN

Perkinsus olseni and P. marinus are classified as notifiable pathogens by the World Organisation for Animal Health and are known to cause perkinsosis in a variety of molluscs globally. Mass mortalities due to these parasites in farms and in the wild have been a recurrent issue. Diagnosis for these protozoans is currently done using Ray's fluid thioglycollate medium method followed by optical microscopy or molecular assays. Both require a high level of skill and are time-consuming. An immunoassay method would make the diagnosis of perkinsosis quicker and cheaper. The present study used mass spectrometry-based proteomics to investigate common hypothetical surface peptides between different geographical isolates of P. olseni, which could be used to develop immunoassays in the future. Two peptides were identified: POLS_08089, which is a 42.7 kDa peptide corresponding to the 60S ribosomal subunit protein L4; and POLS_15916, which is a conserved hypothetical protein of 55.6 kDa. The identification of peptides may allow the development of immunoassays through a more targeted approach.


Asunto(s)
Alveolados , Animales , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Péptidos/química
6.
Dev Neurorehabil ; 27(1-2): 27-33, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38676395

RESUMEN

This paper explores whether a structured history-taking tool yields useful descriptions of children's looking skills. Parents of 32 children referred to a specialist communication clinic reported their child's looking skills using the Functional Vision for Communication Questionnaire (FVC-Q), providing descriptions of single object fixation, fixation shifts between objects and fixation shifts from object to person. Descriptions were compared with clinical assessment. 24/32 children were reported to have some limitation in fixation. Limitation was subsequently seen in 30/32 children. Parental report and assessment agreed fully in 23/32 (72%). The largest area of discrepancy was object-person fixation shifts, with five children not observed to show this behavior despite its being reported. Findings indicate a structured questionnaire yields description of fixations, which correspond well with clinical assessment. Descriptions supported discussion between parents and clinicians. It is proposed that the FVC-Q is a valuable tool in supporting clinicians in eliciting information about fixation skills.


Asunto(s)
Comunicación , Padres , Humanos , Femenino , Niño , Encuestas y Cuestionarios , Masculino , Preescolar , Fijación Ocular/fisiología , Adolescente , Anamnesis
7.
J Child Health Care ; : 13674935241242824, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38590229

RESUMEN

Increasing use of paediatric long-term ventilation (LTV) has been reported around the world over the last two decades and it is anticipated that use of this medical intervention will continue to grow. Research has shown that children who use LTV have risk factors for feeding and swallowing difficulties which result in long-term reliance on non-oral feeding methods. This Patient and Public Involvement (PPI) activity explored experiences of parents of children with LTV on their children's feeding and swallowing journeys. Individual and group interviews with seven parents were conducted. Interview data was then analysed using content analysis. Families discussed a range of themes including impacts on their family, facilitators and barriers to feeding and swallowing journeys, speech and language therapy (SLT) support, their family's healthcare journey in relation to quality of life and future directions for research. This study highlighted potential key areas to explore when identifying ways to improve SLT care and research in feeding and swallowing for children who use LTV.

8.
Nat Chem ; 16(7): 1133-1140, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38459234

RESUMEN

Graphene nanoribbons (GNRs), nanometre-wide strips of graphene, are promising materials for fabricating electronic devices. Many GNRs have been reported, yet no scalable strategies are known for synthesizing GNRs with metal atoms and heteroaromatic units at precisely defined positions in the conjugated backbone, which would be valuable for tuning their optical, electronic and magnetic properties. Here we report the solution-phase synthesis of a porphyrin-fused graphene nanoribbon (PGNR). This PGNR has metalloporphyrins fused into a twisted fjord-edged GNR backbone; it consists of long chains (>100 nm), with a narrow optical bandgap (~1.0 eV) and high local charge mobility (>400 cm2 V-1 s-1 by terahertz spectroscopy). We use this PGNR to fabricate ambipolar field-effect transistors with appealing switching behaviour, and single-electron transistors displaying multiple Coulomb diamonds. These results open an avenue to π-extended nanostructures with engineerable electrical and magnetic properties by transposing the coordination chemistry of porphyrins into graphene nanoribbons.

9.
PLoS One ; 19(2): e0287872, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38386657

RESUMEN

BACKGROUND: The last three decades have seen a growth in the number of children requiring long-term ventilation. Children with long-term ventilation present with underlying respiratory and neurological conditions that place them at risk of feeding and swallowing difficulties. To date, a scoping review or systematic review investigating the feeding and swallowing outcomes of children with long-term ventilation needs has not been conducted. AIMS: This paper describes a protocol for a scoping review of the feeding and swallowing outcomes of children receiving long-term ventilation. METHODS: This scoping review protocol will utilize the Joanna Briggs Institute scoping review methodology guideline. Our review will focus on the feeding and swallowing outcomes of children aged 0 to 18 years with long-term ventilation needs. A full search strategy initially created by the authors and a research librarian was conducted on the PubMed database. Following this, pilot testing took place to determine discrepancies in eligibility criteria. A full search strategy will be conducted across several databases. A data extraction form has been developed by the authors and will be used during the scoping review process. DISCUSSION: This protocol has been created to provide a rigorous and comprehensive basis for undertaking a scoping review. All necessary steps have been completed in order to commence the scoping review. REGISTRATION: This scoping review protocol was registered on Open Science Framework on the 26th November 2021 (Registration DOI 10.17605/OSF.IO/NQBPD).


Asunto(s)
Deglución , Respiración Artificial , Humanos , Niño , Respiración Artificial/efectos adversos , Respiración Artificial/métodos , Deglución/fisiología , Lactante , Preescolar , Adolescente , Trastornos de Deglución/terapia , Recién Nacido , Revisiones Sistemáticas como Asunto
10.
Angew Chem Int Ed Engl ; 63(14): e202400103, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38230920

RESUMEN

Strained macrocycles display interesting properties, such as conformational rigidity, often resulting in enhanced π-conjugation or enhanced affinity for non-covalent guest binding, yet they can be difficult to synthesize. Here we use computational modeling to design a template to direct the formation of an 18-porphyrin nanoring with direct meso-meso bonds between the porphyrin units. Coupling of a linear 18-porphyrin oligomer in the presence of this template gives the target nanoring, together with an unexpected 36-porphyrin ring by-product. Scanning tunneling microscopy (STM) revealed the elliptical conformations and flexibility of these nanorings on a Au(111) surface.

11.
Dysphagia ; 39(4): 666-683, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38180625

RESUMEN

The last two decades have seen increasing use of long-term ventilation (LTV) as an intervention in childhood. Children who use LTV have many risk factors for feeding and swallowing difficulties, including their underlying respiratory and/or neurological etiology, long hospitalizations, medical interventions, and limited exposure to oral feeding experiences. This review aimed to answer two questions: 1) 'What specific swallowing and feeding characteristics do these children experience?'; and 2) 'What impacts do these swallowing and feeding characteristics have on health status and quality of life?'. Texts were identified across bibliographic databases, reference lists, and grey literature. Studies were analyzed according to ventilation, feeding and swallowing, assessment and intervention, and quality of life parameters. Overall, 1919 papers were screened, with 31 papers included in the final data extraction process. A range of feeding and swallowing characteristics were observed, including oral secretion management difficulties, oral aversion, swallowing difficulties, and clinical signs of aspiration. Non-oral feeding was found to be the primary feeding method used. Little information on health status and quality of life was reported in scoping review texts. Children with LTV needs present with a range of feeding and swallowing concerns, and non-oral feeding is common. Further research is needed to understand the feeding and swallowing journey of this population. This will assist in future service planning and delivery, and in turn contribute to improving patient outcomes and quality of life.


Asunto(s)
Trastornos de Deglución , Deglución , Calidad de Vida , Respiración Artificial , Humanos , Trastornos de Deglución/terapia , Trastornos de Deglución/etiología , Trastornos de Deglución/fisiopatología , Niño , Deglución/fisiología , Respiración Artificial/efectos adversos , Respiración Artificial/métodos , Preescolar , Femenino , Masculino
12.
Brain ; 147(4): 1206-1215, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38085047

RESUMEN

Low serum levels of 25-hydroxyvitamin D [25(OH)D] and low sunlight exposure are known risk factors for the development of multiple sclerosis. Add-on vitamin D supplementation trials in established multiple sclerosis have been inconclusive. The effects of vitamin D supplementation to prevent multiple sclerosis is unknown. We aimed to test the hypothesis that oral vitamin D3 supplementation in high-risk clinically isolated syndrome (abnormal MRI, at least three T2 brain and/or spinal cord lesions), delays time to conversion to definite multiple sclerosis, that the therapeutic effect is dose-dependent, and that all doses are safe and well tolerated. We conducted a double-blind trial in Australia and New Zealand. Eligible participants were randomized 1:1:1:1 to placebo, 1000, 5000 or 10 000 international units (IU) of oral vitamin D3 daily within each study centre (n = 23) and followed for up to 48 weeks. Between 2013 and 2021, we enrolled 204 participants. Brain MRI scans were performed at baseline, 24 and 48 weeks. The main study outcome was conversion to clinically definite multiple sclerosis based on the 2010 McDonald criteria defined as either a clinical relapse or new brain MRI T2 lesion development. We included 199 cases in the intention-to-treat analysis based on assigned dose. Of these, 116 converted to multiple sclerosis by 48 weeks (58%). Compared to placebo, the hazard ratios (95% confidence interval) for conversion were 1000 IU 0.87 (0.50, 1.50); 5000 IU 1.37 (0.82, 2.29); and 10 000 IU 1.28 (0.76, 2.14). In an adjusted model including age, sex, latitude, study centre and baseline symptom number, clinically isolated syndrome onset site, presence of infratentorial lesions and use of steroids, the hazard ratios (versus placebo) were 1000 IU 0.80 (0.45, 1.44); 5000 IU 1.36 (0.78, 2.38); and 10 000 IU 1.07 (0.62, 1.85). Vitamin D3 supplementation was safe and well tolerated. We did not demonstrate reduction in multiple sclerosis disease activity by vitamin D3 supplementation after a high-risk clinically isolated syndrome.


Asunto(s)
Enfermedades Desmielinizantes , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/tratamiento farmacológico , Vitamina D/uso terapéutico , Vitaminas/uso terapéutico , Colecalciferol/uso terapéutico , Colecalciferol/efectos adversos , Calcifediol , Enfermedades Desmielinizantes/diagnóstico por imagen , Enfermedades Desmielinizantes/tratamiento farmacológico , Método Doble Ciego
13.
Augment Altern Commun ; : 1-12, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38047627

RESUMEN

Children who use augmentative and alternative communication (AAC) are multimodal communicators. However, in classroom interactions involving children and staff, achieving mutual understanding and accomplishing task-oriented goals by attending to the child's unaided AAC can be challenging. This study draws on excerpts of video recordings of interactions in a classroom for 6-9-year-old children who used AAC to explore how three child participants used the range of multimodal resources available to them - vocal, movement-based, and gestural, technological, temporal - to shape (and to some degree, co-control) classroom interactions. Our research was concerned with examining achievements and problems in establishing a sense of common ground and the realization of child agency. Through detailed multimodal analysis, this paper renders visible different types of practices rejecting a request for clarification, drawing new parties into a conversation, disrupting whole-class teacher talk-through which the children in the study voiced themselves in persuasive ways. It concludes by suggesting that multimodal accounts paint a more nuanced picture of children's resourcefulness and conversational asymmetry that highlights children's agency amidst material, semiotic, and institutional constraints.

14.
Disabil Rehabil Assist Technol ; : 1-8, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-38112177

RESUMEN

PURPOSE: Little is known about how children learn to control eye-gaze technology, and clinicians lack information to guide decision-making. This paper examines whether typically developing 2-3 year olds can infer for themselves the causal mechanisms by which eye-gaze technology is controlled, whether a teaching intervention based on causal language improves performance and how their performance compares to the same task accessed via a touchscreen.Methods and materials: Typically developing children's (n = 9, Mean Age 28.7 months) performance on a cause and effect game presented on eye-gaze and touchscreen devices was compared. The game was presented first with no specific instruction on how to control the devices. This was followed by a subsequent presentation with explicit instruction about how the access methods worked, using a causal language approach. A final presentation examined whether children had retained any learning. RESULTS: Performance in the eye-gaze condition without instruction (42.5% successful trials) was significantly below performance in the corresponding touchscreen condition (75%). However, when causal language instruction was added, performance with both access methods rose to comparable levels (90.7% eye-gaze and 94.6% touchscreen success). Performance gains were not retained post-intervention. CONCLUSIONS: Although 2-3 years in the study could make use of eye-gaze technology with support, this study found no evidence that these children could infer the causal mechanisms of control independently or intuitively. The lack of spatial contiguity and the comparative lack of feedback from eye-gaze devices are discussed as possible contributory factors.


There are challenges in young children inferring for themselves the causal link between eye movements and control of an eye-gaze device.Explicit instruction may improve children's performance in a specific task, but it is debatable whether this translates to the establishment of causal mechanisms for control of the device.Clinicians should be cautious of making assumptions about what children are learning from activities claiming to teach cause and effect or other foundational eye-gaze control skills.

15.
Augment Altern Commun ; 39(4): 293-301, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37671918

RESUMEN

The present study investigated the relationship between lexicon and grammar in individuals who use graphic symbol-based aided augmentative and alternative communication (AAC). Data came from 60 transcripts of generalization sessions that were part of two previous intervention studies, aimed at improving the expressive vocabulary and grammar of 12 children and youth who used graphic symbol-based AAC. The specific aims of the current study were to (a) describe vocabulary composition across different levels of expressive vocabulary and (b) analyze the relationship between global measures of expressive vocabulary and the use of grammar in individuals who use aided AAC. A series of multiple linear mixed effect regression analyses showed a positive predictive association between overall vocabulary size and the use of closed-class words, and a positive relationship between the use of verbs and the use of closed-class words. Additionally, the use of verbs had a significant positive association with the use of inflectional morphology, while the use of nouns did not. Theoretical and practical implications of these findings are discussed.


Asunto(s)
Equipos de Comunicación para Personas con Discapacidad , Trastornos de la Comunicación , Humanos , Niño , Adolescente , Lingüística , Vocabulario , Lenguaje
16.
Am J Physiol Lung Cell Mol Physiol ; 325(5): L628-L637, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37697929

RESUMEN

Antenatal steroid therapy is the standard of care for women at imminent risk of preterm delivery. Current dosing regimens use suprapharmacological doses to achieve extended fetal steroid exposures. We aimed to determine the lowest fetal plasma betamethasone concentration sufficient to achieve functional preterm lung maturation. Ewes with single fetuses underwent surgery to install a fetal jugular catheter. Adopting a stepwise design, ewes were randomized to either a saline-only group (negative control group; n = 9) or one of four betamethasone treatment groups. Each betamethasone group fetus received a fetal intravenous infusion to target a constant plasma betamethasone level of either 1) 2 ng/mL (2 ng/mL positive control group, n = 9); 2) 1 ng/mL, (1 ng/mL group, n = 10); 3) 0.5 ng/mL (0.5 ng/mL group, n = 10); or 4) 0.25 ng/mL (0.25 ng/mL group, n = 10). Fetuses were infused for 48 h, delivered, and ventilated. The positive control group, negative control group, and mid-point 0.5 ng/mL group animals were tested first. An interim analysis informed the final betamethasone group tested. Positive control group animals had large, statistically significant improvements in respiratory function. Based on an interim analysis, the 1.0 ng/mL group was studied in favor of the 0.25 ng/mL group. Treatment efficacy was progressively lost at plasma betamethasone concentrations lower than 2 ng/mL. We demonstrated that the acute respiratory benefit conveyed by antenatal steroid exposure in the fetal sheep is progressively lost when constant fetal plasma betamethasone concentrations are reduced below a targeted value of 2 ng/mL.NEW & NOTEWORTHY Lung maturation benefits in preterm lambs were progressively lost when fetal plasma betamethasone concentrations fell below 2 ng/mL. The effective floor threshold for a robust, lung-maturing exposure likely lies between 1 and 2 ng betamethasone per milliliter of plasma. Hypothalamic pituitary adrenal axis signaling and immunocyte populations remained materially disrupted at subtherapeutic steroid concentrations. These data demonstrate the potential to improve antenatal steroid therapy using reduced dose regimens informed by glucocorticoid pharmacokinetics and pharmacodynamics.

17.
Anticancer Drugs ; 34(10): 1122-1131, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37067993

RESUMEN

Histone lysine demethylase 4 (KDM4) is an epigenetic regulator that facilitates the transition between transcriptionally silent and active chromatin states by catalyzing the removal of methyl groups on histones H3K9, H3K36, and H1.4K26. KDM4 overamplification or dysregulation has been reported in various cancers and has been shown to drive key processes linked to tumorigenesis, such as replicative immortality, evasion of apoptosis, metastasis, DNA repair deficiency, and genomic instability. KDM4 also plays a role in epigenetic regulation of cancer stem cell renewal and has been linked to more aggressive disease and poorer clinical outcomes. The KDM4 family is composed of four main isoforms (KDM4A-D) that demonstrate functional redundancy and cross-activity; thus, selective inhibition of one isoform appears to be ineffective and pan-inhibition targeting multiple KDM4 isoforms is required. Here, we describe TACH101, a novel, small-molecule pan-inhibitor of KDM4 that selectively targets KDM4A-D with no effect on other KDM families. TACH101 demonstrated potent antiproliferative activity in cancer cell lines and organoid models derived from various histologies, including colorectal, esophageal, gastric, breast, pancreatic, and hematological malignancies. In vivo , potent inhibition of KDM4 led to efficient tumor growth inhibition and regression in several xenograft models. A reduction in the population of tumor-initiating cells was observed following TACH101 treatment. Overall, these observations demonstrate the broad applicability of TACH101 as a potential anticancer agent and support its advancement into clinical trials.


Asunto(s)
Histona Demetilasas , Neoplasias , Humanos , Histona Demetilasas/genética , Histona Demetilasas/metabolismo , Histona Demetilasas/uso terapéutico , Histona Demetilasas con Dominio de Jumonji/genética , Histona Demetilasas con Dominio de Jumonji/metabolismo , Epigénesis Genética , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/uso terapéutico
18.
Angew Chem Int Ed Engl ; 62(18): e202302114, 2023 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-36877745

RESUMEN

Rings of porphyrins mimic natural light-harvesting chlorophyll arrays and offer insights into electronic delocalization, providing a motivation for creating larger nanorings with closely spaced porphyrin units. Here, we demonstrate the first synthesis of a macrocycle consisting entirely of 5,15-linked porphyrins. This porphyrin octadecamer was constructed using a covalent six-armed template, made by cobalt-catalyzed cyclotrimerization of an H-shaped tolan with porphyrin trimer ends. The porphyrins around the circumference of the nanoring were linked together by intramolecular oxidative meso-meso coupling and partial ß-ß fusion, to give a nanoring consisting of six edge-fused zinc(II) porphyrin dimer units and six un-fused nickel(II) porphyrins. STM imaging on a gold surface confirms the size and shape of the spoked 18-porphyrin nanoring (calculated diameter: 4.7 nm).

19.
Neurochem Int ; 163: 105487, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36657721

RESUMEN

microRNA (miRNA) are important regulators of gene expression. miRNA have the potential as a treatment to modulate genes, pathways and cells involved in ischemic stroke. In this review, we specifically present miRNA in stroke as a treatment to decrease thrombosis, reduce blood brain barrier (BBB) disruption and hemorrhagic transformation (HT), modulate inflammation, and modify angiogenesis. miRNA as a treatment for stroke is an emerging area with evidence from animal studies demonstrating its potential. While no miRNA is currently approved for human use, several have shown promise in clinical trials to treat medical conditions, such as miR-122 for hepatitis C. The role of miRNA as a treatment for specific applications in ischemic stroke is presented including a discussion of the benefits and barriers of miRNA as a treatment, and directions for future advancement.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , MicroARNs , Accidente Cerebrovascular , Animales , Humanos , MicroARNs/metabolismo , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/tratamiento farmacológico , Barrera Hematoencefálica/metabolismo , Inflamación/metabolismo , Isquemia Encefálica/terapia , Isquemia Encefálica/tratamiento farmacológico
20.
Langenbecks Arch Surg ; 408(1): 32, 2023 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-36645510

RESUMEN

BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) is relatively a new approach for clearing choledocholithiasis. The aim of this study is to assess the safety of this approach to clearing common bile duct (CBD) stones on an index admission including emergency setting. METHODS: Retrospective data collection and analysis were carried out for 207 consecutive cases of LCBDE performed in Royal Cornwall Hospital over 6 years (2015-2020). Patients were divided into two groups (Index admission vs elective) then both groups compared. RESULTS: A total of 207 cases of LCBDE were performed in our unit during the time period. One hundred twenty-two operations were performed on the index admission and 85 on a subsequent elective list. Mean operative time was 146 ± 64 min in the index admission group and 145 ± 65 min in the elective group (p = 0.913). Length of stay post-operatively was 3.3 ± 6.3 days in the index admission cases and 3.5 ± 4.6 days after elective cases. Successful clearance was achieved at the end of the operation in 116 patients in the index admission group, clearance failed in one case and negative exploration in 5 patients. In the elective group 83 patients had a successful clearance at the end of the operation, and 2 patients has had a negative exploration. Twelve patients (index admission group) and 8 patients of the elective cases required post-operative Endoscopic Retrograde Cholangiopancreatography (ERCP) to manage retained stones, recurrent stones and bile leak (p = 0.921). Three patients required re-operation for post-operative complications in each group. CONCLUSION: Common bile duct exploration in index admission is safe with high success rate if performed by well-trained surgeons with advanced laparoscopic skills.


Asunto(s)
Colecistectomía Laparoscópica , Coledocolitiasis , Cálculos Biliares , Laparoscopía , Humanos , Conducto Colédoco/cirugía , Estudios Retrospectivos , Hospitales Generales , Coledocolitiasis/cirugía , Cálculos Biliares/cirugía , Colangiopancreatografia Retrógrada Endoscópica , Tiempo de Internación
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