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1.
Pak J Med Sci ; 38(8): 2324-2330, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36415252

RESUMEN

Objectives: Chorioretinal diseases requiring the use of anti-vascular endothelial growth (anti-VEGF) injections often occur in both eyes simultaneously. This can necessitate injecting both eyes together rather than one eye at a time. The purpose of the study was to determine whether simultaneous bilateral intravitreal injections of anti-VEGF agents are safe when administered in an operation theatre setting. Methods: Retrospective review of data was conducted. Single center study conducted in a tertiary care hospital in Karachi Pakistan. Approximately 30,000 eyes that received anti-VEGF injection during a 10-year study period were included (March 2008-February 2018). Patients who were lost to follow up prior to completion of treatment were excluded. Consecutive sampling technique was employed. The patients who received bilateral anti-VEGF injections were analysed separately from the ones who received unilateral injections. All injections were administered in operating theatre setting. The rate of endophthalmitis was measured in each group. Results: A total of 30,258 injections were administered of which 15,338 were bilateral injections. Four cases (4/30,258, 0.013%) of endophthalmitis occurred during the study period. Only one case (1/15,338, 0.0065%) of endophthalmitis occurred after the administration of simultaneous bilateral anti-VEGF injections. Conclusions: Administration of simultaneous bilateral anti-VEGF injections was safe in our population.

2.
Hum Mol Genet ; 27(2): 373-384, 2018 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-29177465

RESUMEN

Attempts have been made to treat nonsense-associated genetic disorders by chemical agents and hence an improved mechanistic insight into the decoding of readthrough signals is essential for the identification and characterisation of factors for the treatment of these disorders. To identify either novel compounds or genes that modulate translation readthrough, we have employed dual reporter-based high-throughput screens that use enzymatic and fluorescence activities and screened bioactive National Institute of Neurological Disease Syndrome (NINDS) compounds (n = 1000) and siRNA (n = 288) libraries. Whilst siRNAs targeting kinases such as CSNK1G3 and NME3 negatively regulate readthrough, neither the bioactive NINDS compounds nor PTC124 promote readthrough. Of note, PTC124 has previously been shown to promote readthrough. Furthermore, the impacts of G418 on the components of eukaryotic selenocysteine incorporation machinery have also been investigated. The selenocysteine machinery decodes the stop codon UGA specifying selenocysteine in natural selenoprotein genes. We have found that the eukaryotic SelC gene promotes the selenocysteine insertion sequence (SECIS)-mediated readthrough but inhibits the readthrough activity induced by G418. We have previously reported that SECIS-mediated readthrough at UGA codons follows a non-processive mechanism. Here, we show that G418-mediated promotion of readthrough also occurs through a non-processive mechanism which competes with translation termination. Based on our observations, we suggest that proteins generated through a non-processive mechanism may be therapeutically beneficial for the resolution of nonsense-associated genetic disorders.


Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Bibliotecas de Moléculas Pequeñas/farmacología , Aminoglicósidos/metabolismo , Secuencia de Bases , Caseína Quinasa Ialfa/metabolismo , Codón sin Sentido , Codón de Terminación , Humanos , Nucleósido Difosfato Quinasas NM23/metabolismo , Conformación de Ácido Nucleico , Oxadiazoles/farmacología , Terminación de la Cadena Péptídica Traduccional , Biosíntesis de Proteínas , Inhibidores de la Síntesis de la Proteína , ARN Mensajero/genética , ARN Interferente Pequeño/genética
3.
J Pak Med Assoc ; 70(7): 1279-1281, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32799293

RESUMEN

A 25-year-old male presented with a complaint of acute visual loss in his right eye for two days. There was a history of visual loss in the left eye six months ago. Comprehensive eye examination showed evidence of posterior uveitis, and a placoid lesion on the right fundus. Further physical examination showed maculopapular rashes on the upper back which was highly suggestive of syphilis. Blood tests for venereal disease research laboratory (VDRL) test and fluorescent treponemal antibody absorption (FTA-ABS) test were ordered, which were both positive. Ocular syphilis should be suspected in all cases of uveitis. Early diagnosis and prompt treatment with appropriate antibiotics can prevent permanent visual loss.


Asunto(s)
Coriorretinitis , Infecciones Bacterianas del Ojo , Sífilis , Adulto , Coriorretinitis/diagnóstico , Coriorretinitis/tratamiento farmacológico , Infecciones Bacterianas del Ojo/diagnóstico , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Angiografía con Fluoresceína , Fondo de Ojo , Humanos , Masculino , Sífilis/complicaciones , Sífilis/diagnóstico , Sífilis/tratamiento farmacológico
4.
PLOS Digit Health ; 3(5): e0000443, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38728363

RESUMEN

The advent of artificial intelligence (AI) technologies has emerged as a promising solution to enhance healthcare efficiency and improve patient outcomes. The objective of this study is to analyse the knowledge, attitudes, and perceptions of healthcare professionals in Pakistan about AI in healthcare. We conducted a cross-sectional study using a questionnaire distributed via Google Forms. This was distributed to healthcare professionals (e.g., doctors, nurses, medical students, and allied healthcare workers) working or studying in Pakistan. Consent was taken from all participants before initiating the questionnaire. The questions were related to participant demographics, basic understanding of AI, AI in education and practice, AI applications in healthcare systems, AI's impact on healthcare professions and the socio-ethical consequences of the use of AI. We analyzed the data using Statistical Package for Social Sciences (SPSS) statistical software, version 26.0. Overall, 616 individuals responded to the survey while n = 610 (99.0%) of respondents consented to participate. The mean age of participants was 32.2 ± 12.5 years. Most of the participants (78.7%, n = 480) had never received any formal sessions or training in AI during their studies/employment. A majority of participants, 70.3% (n = 429), believed that AI would raise more ethical challenges in healthcare. In all, 66.4% (n = 405) of participants believed that AI should be taught at the undergraduate level. The survey suggests that there is insufficient training about AI in healthcare in Pakistan despite the interest of many in this area. Future work in developing a tailored curriculum regarding AI in healthcare will help bridge the gap between the interest in use of AI and training.

5.
Diabetes Res Clin Pract ; 216: 111815, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39173680

RESUMEN

Type 2 diabetes mellitus (T2DM) and pre-diabetes (pre-DM) are significant health concerns in Pakistan. This systematic review and meta-analysis estimate the prevalence of T2DM and pre-DM, assessing regional, gender, and urban-rural differences. We searched PubMed, Scopus, Cochrane, and PakMediNet databases, identifying 3478 articles. After screening, 17 studies from 1995 to 2018 were included. The pooled prevalence of T2DM and pre-DM in Pakistan was found to be 10.0 % and 11.0 %, respectively. This equates to approximately 24 million individuals with T2DM and 26 million with pre-DM, totaling 50 million affected. Rural areas showed higher T2DM prevalence post-2000, with an odds ratio (OR) of 1.25 (95 % CI: 0.73 to 2.14). Gender analysis revealed a slightly higher, though statistically insignificant, prevalence of T2DM in females and a significantly higher prevalence of pre-DM in males (OR: 0.79, 95 % CI: 0.63 to 0.98). Regionally, Punjab had the highest T2DM prevalence (16 %), followed by Baluchistan (15 %), Sindh (14 %), and Khyber Pakhtunkhwa (KPK) (11 %). There is a substantial burden of T2DM and pre-DM in Pakistan, with significant regional and gender differences. Targeted interventions and resource allocation are needed to address the rising prevalence of diabetes, focusing on early detection and lifestyle modifications.


Asunto(s)
Diabetes Mellitus Tipo 2 , Estado Prediabético , Humanos , Pakistán/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Prevalencia , Estado Prediabético/epidemiología , Masculino , Femenino , Población Rural/estadística & datos numéricos
6.
BMJ Open ; 14(3): e079513, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38479742

RESUMEN

INTRODUCTION: Diabetes mellitus (DM) is a chronic metabolic disorder characterised by hyperglycaemia resulting from defects in insulin secretion, insulin action or both. As a major global health concern, its prevalence has been steadily increasing. Pakistan, is no exception to this trend, facing a growing burden of non-communicable diseases including DM. This research aims to comprehensively assess the prevalence of DM, and disparities between rural and urban populations as well as between men and women in Pakistan. METHODS AND ANALYSIS: The systematic review will follow Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and will aim to assess DM prevalence in Pakistan. A comprehensive search strategy will be applied to databases like PubMed, Scopus, Cochrane, PakMediNet and CINAHL from inception up to 1st April 2024. We will include studies that focus on diabetes prevalence in the general population, employing WHO or American Diabetes Association criteria for diagnosis of DM. Cross-sectional studies, cohort studies and population-based surveys with a sample size ≥500, in English will be considered. Data extraction will be done as per a predefined proforma which will include study details such as demographics, prevalence data and methodology. A meta-analysis will be performed using a random effect model with an inverse variance weighted method. I2 statistics will be used to examine heterogeneity, and subgroup analyses will be performed. ETHICS AND DISSEMINATION: The findings from the systematic review will be shared by publishing them in a peer-reviewed journal and showcasing them at pertinent conferences. Our analysis will be based on aggregated data and will not involve individual patient information, thus eliminating the need for ethical clearance. PROSPERO REGISTRATION NUMBER: CRD42023453085.


Asunto(s)
Diabetes Mellitus , Hiperglucemia , Masculino , Humanos , Femenino , Estudios Transversales , Pakistán/epidemiología , Revisiones Sistemáticas como Asunto , Diabetes Mellitus/epidemiología , Diabetes Mellitus/diagnóstico , Proyectos de Investigación , Metaanálisis como Asunto
7.
J Biol Chem ; 287(16): 13084-93, 2012 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-22308025

RESUMEN

It is well known that the renin-angiotensin system contributes to left ventricular hypertrophy and fibrosis, a major determinant of myocardial stiffness. TGF-ß1 and renin-angiotensin system signaling alters the fibroblast phenotype by promoting its differentiation into morphologically distinct pathological myofibroblasts, which potentiates collagen synthesis and fibrosis and causes enhanced extracellular matrix deposition. However, the atrial natriuretic peptide, which is induced during left ventricular hypertrophy, plays an anti-fibrogenic and anti-hypertrophic role by blocking, among others, the TGF-ß-induced nuclear localization of Smads. It is not clear how the hypertrophic and fibrotic responses are transcriptionally regulated. CLP-1, the mouse homolog of human hexamethylene bis-acetamide inducible-1 (HEXIM-1), regulates the pTEFb activity via direct association with pTEFb causing inhibition of the Cdk9-mediated serine 2 phosphorylation in the carboxyl-terminal domain of RNA polymerase II. It was recently reported that the serine kinase activity of Cdk9 not only targets RNA polymerase II but also the conserved serine residues of the polylinker region in Smad3, suggesting that CLP-1-mediated changes in pTEFb activity may trigger Cdk9-dependent Smad3 signaling that can modulate collagen expression and fibrosis. In this study, we evaluated the role of CLP-1 in vivo in induction of left ventricular hypertrophy in angiotensinogen-overexpressing transgenic mice harboring CLP-1 heterozygosity. We observed that introduction of CLP-1 haplodeficiency in the transgenic α-myosin heavy chain-angiotensinogen mice causes prominent changes in hypertrophic and fibrotic responses accompanied by augmentation of Smad3/Stat3 signaling. Together, our findings underscore the critical role of CLP-1 in remodeling of the genetic response during hypertrophy and fibrosis.


Asunto(s)
Angiotensina II/metabolismo , Cardiomegalia/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Remodelación Ventricular/genética , Angiotensinógeno/genética , Animales , Cardiomegalia/genética , Cardiomegalia/patología , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Fibroblastos/metabolismo , Fibroblastos/patología , Fibrosis/metabolismo , Fibrosis/patología , Heterocigoto , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Cadenas Pesadas de Miosina/genética , Proteínas de Unión al ARN , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/fisiología , Proteína smad3/metabolismo , Transcripción Genética/fisiología
8.
Mol Cell Biochem ; 384(1-2): 59-69, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23963993

RESUMEN

Rotenone, a commonly used pesticide, is well documented to induce selective degeneration in dopaminergic neurons and motor dysfunction. Such rotenone-induced neurodegenration has been primarily suggested through mitochondria-mediated apoptosis and reactive oxygen species (ROS) generation. But the status of rotenone induced changes in liver, the major metabolic site is poorly investigated. Thus, the present investigation was aimed to study the oxidative stress-induced cytotoxicity and apoptotic cell death in human liver cells-HepG2 receiving experimental exposure of rotenone (12.5-250 µM) for 24 h. Rotenone depicted a dose-dependent cytotoxic response in HepG2 cells. These cytotoxic responses were in concurrence with the markers associated with oxidative stress such as an increase in ROS generation and lipid peroxidation as well as a decrease in the glutathione, catalase, and superoxide dismutase levels. The decrease in mitochondrial membrane potential also confirms the impaired mitochondrial activity. The events of cytotoxicity and oxidative stress were found to be associated with up-regulation in the expressions (mRNA and protein) of pro-apoptotic markers viz., p53, Bax, and caspase-3, and down-regulation of anti-apoptotic marker Bcl-2. The data obtain in this study indicate that rotenone-induced cytotoxicity in HepG2 cells via ROS-induced oxidative stress and mitochondria-mediated apoptosis involving p53, Bax/Bcl-2, and caspase-3.


Asunto(s)
Apoptosis/efectos de los fármacos , Insecticidas/farmacología , Hígado/patología , Estrés Oxidativo/efectos de los fármacos , Rotenona/farmacología , Caspasa 3/biosíntesis , Caspasa 3/metabolismo , Catalasa/metabolismo , Línea Celular Tumoral , Glutatión/metabolismo , Células Hep G2 , Humanos , Peroxidación de Lípido/efectos de los fármacos , Hígado/enzimología , Hígado/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Transcripción Genética/efectos de los fármacos , Proteína p53 Supresora de Tumor/biosíntesis , Proteína p53 Supresora de Tumor/metabolismo , Proteína X Asociada a bcl-2/biosíntesis , Proteína X Asociada a bcl-2/metabolismo
9.
Reprod Domest Anim ; 48(3): 500-5, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23106681

RESUMEN

The successful outcome of an insemination is a combination of both male and female fertility-linked factors. We investigated the first service conception rate of cows at artificial insemination (AI) in the smallholder dairy farms in Bangladesh. Frozen straws were prepared from ejaculates of Bos indicus (n = 7) and Bos indicus × Bos taurus (n = 7) AI bulls. Fertility was determined from 6101 first services in cows that were performed by 18 technicians in four regions between April 2004 and March 2005. Pregnancy was diagnosed by rectal palpation between 60 and 90 days post-insemination. The Asian version of Artificial Insemination Database Application (AIDA ASIA) was used for bulls-, cows- and AI-related data recording, and later retrieved for analysis. The mean ± SD number of inseminations performed from individual bulls and their conception rates were 436.0 ± 21.6 and 50.7 ± 1.9%, respectively. Logistic regression demonstrated body condition scores (BCS), heat detection signs, months of AI and their interactions had greatest effects (odds ratios: 1.24-16.65, p < 0.04-0.001) on first service conception rate in cows. Fertility differed (p < 0.02-0.001) between the regions, previous calving months, months of AI, BCS, parity and heat detection signs of cows. Inseminations based on mounting activity (n = 2352), genital discharge (n = 3263) and restlessness and/or other signs (n = 486) yielded a conception rate of 53.6%, 48.8% and 50.1%, respectively (p < 0.05). Conception rate between technicians ranged between 43.4% and 58.6% (p < 0.05). The days interval from calving to first service (overall mean ± SD = 153.4 ± 80.6) had relationship (p < 0.001) with BCS, months of previous calving and parity of the cows. Fertility at AI in smallholder farms can be improved by training farmers on nutrition and reproductive management of the cows.


Asunto(s)
Crianza de Animales Domésticos , Bovinos/fisiología , Industria Lechera , Preñez , Animales , Bangladesh , Femenino , Inseminación Artificial/veterinaria , Masculino , Embarazo
10.
Diabetes Res Clin Pract ; 205: 110943, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37805002

RESUMEN

AIMS: Diabetic retinopathy (DR) is a major cause of blindness globally, early detection is critical to prevent vision loss. Traditional screening that, rely on human experts are, however, costly, and time-consuming. The purpose of this systematic review is to assess the diagnostic accuracy of smartphone-based artificial intelligence(AI) systems for DR detection. METHODS: Literature review was conducted on MEDLINE, Embase, Scopus, CINAHL Plus, and Cochrane from inception to December 2022. We included diagnostic test accuracy studies evaluating the use of smartphone-based AI algorithms for DR screening in patients with diabetes, with expert human grader as the reference standard. Random-effects model was used to pool sensitivity and specificity. Any DR(ADR) and referable DR(RDR) were analyzed separately. RESULTS: Out of 968 identified articles, six diagnostic test accuracy studies met our inclusion criteria, comprising 3,931 patients. Four of these studies used the Medios AI algorithm. The pooled sensitivity and specificity for diagnosis of ADR were 88 % and 91.5 % respectively and for diagnosis of RDR were 98.2 % and 81.2 % respectively. The overall risk of bias across the studies was low. CONCLUSIONS: Smartphone-based AI algorithms show high diagnostic accuracy for detecting DR. However, more high-quality comparative studies are needed to evaluate the effectiveness in real-world clinical settings.


Asunto(s)
Diabetes Mellitus , Retinopatía Diabética , Humanos , Inteligencia Artificial , Retinopatía Diabética/diagnóstico , Teléfono Inteligente , Algoritmos , Sensibilidad y Especificidad
11.
Eye (Lond) ; 37(11): 2176-2182, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36517576

RESUMEN

The purpose of this study was to perform a systematic review of existing literature on OCT screening before cataract surgery. Available literature was evaluated and projections on how it could be applied to enhance postoperative outcomes of cataract surgery were summarised. The PubMed, Embase and Cochrane databases were searched for articles pertaining to preoperative OCT screening. Selected articles were qualitatively and quantitatively analysed. Across 9 studies, the addition of OCT macular screening resulted in preoperative detection of macular pathology in 13.7% of eyes that were determined to be normal on fundoscopic examination alone. The types of macular pathology most frequently detected through preoperative OCT screening were interface abnormalities followed by macular degeneration. Comparative analysis of SS-OCT biometer and SD-OCT found that SS-OCT had a sensitivity of 0.48-0.81 in the detection of macular pathology in eyes with pathology diagnosed by SD-OCT. OCT screening prior to cataract surgery results in the detection of occult macular pathology that may influence postoperative visual outcomes in approximately 1 in 10 eyes (13.7%). As a result, OCT screening should be considered in the routine preoperative workup for cataract surgery.


Asunto(s)
Extracción de Catarata , Catarata , Degeneración Macular , Humanos , Tomografía de Coherencia Óptica/métodos , Extracción de Catarata/métodos , Degeneración Macular/diagnóstico , Ojo
12.
Cureus ; 15(5): e39714, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37398741

RESUMEN

PURPOSE: To explore the relationship of gender with laser retinopexy for retinal breaks in the Pakistani population. MATERIALS AND METHODS: This was a 10-year retrospective observational study conducted at Aga Khan University Hospital, Karachi, Pakistan. All consecutive patients who underwent laser retinopexy between January 2009 and December 2018 for a retinal tear or high-risk retinal degeneration (such as lattice degeneration) were included in this study. Data were collected from patients' files. Index eyes with a history of or treatment for retinal detachment were excluded. A structured pro forma was used to collect information. Descriptive statistics were used to explore the relationship between gender and laser retinopexy. RESULTS: We identified 12,457 patients through the coding system of our hospital who underwent various laser procedures from January 2009 to December 2018. Yttrium aluminium garnet (YAG) laser, laser peripheral iridotomy (PI), and laser trabeculoplasty procedures were all excluded. A total of 3,472 patients' files were reviewed for this study, out of which 958 patients met the inclusion criteria. Males accounted for a higher number (n=515, 53.87%). The mean age was 43.99±15.37 years. For exploratory analysis, participants were divided into five age groups: <30 years (24.16%); 31-40 years (16.59%); 41-50 years (19.45%); 51-60 years (26.40%); and >60 years (13.49%). Bilateral laser retinopexy was performed in 48.12% of patients; 24.79% and 27.13% of patients underwent unilateral laser retinopexy for the right and left eyes, respectively. CONCLUSION: In our cohort study, laser retinopexy was more commonly performed in men than in women. The ratio was not significantly different from the prevalence of retinal tears and retinal detachment in the general population, which has a slightly higher male preponderance. We did not find evidence of significant gender bias among patients who underwent laser retinopexy in our study.

13.
BMC Res Notes ; 16(1): 376, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-38115143

RESUMEN

OBJECTIVE: To assess the diagnostic accuracy of the IOLMaster 700 foveal scans to detect foveal pathology compared with a standard swept-source optical coherence tomography (SS-OCT) device. RESULTS: One hundred seventy eye scans of 95 patients were included in the final analyses. Ninety-nine (58.2%) scans were classified as abnormal by SS-OCT. Mean sensitivity of the biometry device was 67.5% (range: 51-84%) and mean specificity was 69.5% (range: 44-95%). Intra-class correlation coefficients were 0.912 and 0.835, for reader 1 and 2, respectively. Area under the curve for receiver operating curve was 0.726. Foveal scans of the IOLMaster 700 can provide clinically useful information. Clinicians should pay attention to the macular scans when reviewing biometry prior to cataract surgery and standard macular OCT should ideally be supplemented in suspicious cases.


Asunto(s)
Extracción de Catarata , Catarata , Cristalino , Oftalmología , Humanos , Extracción de Catarata/métodos , Tomografía de Coherencia Óptica/métodos , Biometría/métodos , Reproducibilidad de los Resultados
14.
Prostate ; 72(9): 1035-44, 2012 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-22095517

RESUMEN

BACKGROUND: Androgen and TGF-ß signaling are important components during the progression of prostate cancer. However, whether common molecular events participate in the activation of these signaling pathways are less understood. METHOD: Hexim 1 expression was detected by immunohistochemistry of human tissue microarrays and TRAMP mouse models. The in vivo significance of Hexim-1 was established by crossing the TRAMP mouse model of prostate cancer with Hexim-1 heterozygous mice. TRAMP C2 cell line was also modified to delete one copy of Hexim-1 gene to generate TRAMP-C2-Hexim-1+/- cell lines. RESULTS: In this report, we observed that Hexim-1 protein expression is absent in normal prostate but highly expressed in adenocarcinoma of the prostate and a characteristic sub-cellular distribution among normal, benign hyperplasia, and adenocarcinoma of the prostate. Heterozygosity of the Hexim-1 gene in the prostate cancer mice model and the TRAMP-C2 cell line, leads to increased Cdk9-dependent serine phosphorylation on protein targets such as the androgen receptor (AR) and the TGF-ß-dependent downstream transcription factors, such as the SMAD proteins. CONCLUSION: Our results suggest that changes in the Hexim-1 protein expression and cellular distribution significantly influences the AR activation and the TGF-ß signaling. Thus, Hexim-1 is likely to play a significant role in prostate cancer progression.


Asunto(s)
Progresión de la Enfermedad , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Receptores Androgénicos/metabolismo , Transducción de Señal/fisiología , Factores de Transcripción/fisiología , Factor de Crecimiento Transformador beta/metabolismo , Animales , Humanos , Masculino , Ratones , Ratones Transgénicos , Fosforilación , Neoplasias de la Próstata/metabolismo , Proteínas de Unión al ARN , Receptores Androgénicos/fisiología , Proteínas Smad/metabolismo , Proteínas Smad/fisiología , Factor de Crecimiento Transformador beta/fisiología
15.
J Cell Sci ; 123(Pt 21): 3789-95, 2010 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-20940258

RESUMEN

Emerging evidence suggests that eukaryotic gene transcription is regulated primarily at the elongation stage by association and dissociation of the inhibitory protein cardiac lineage protein 1 (CLP-1/HEXIM1) from the positive transcription elongation factor b (P-TEFb) complex. It was reported recently that P-TEFb interacts with skeletal muscle-specific regulatory factor, MyoD, suggesting a linkage between CLP-1-mediated control of transcription and skeletal myogenesis. To examine this, we produced CLP-1 knockdown skeletal muscle C2C12 cells by homologous recombination, and demonstrated that the C2C12 CLP-1 +/- cells failed to differentiate when challenged by low serum in the medium. We also showed that CLP-1 interacts with both MyoD and histone deacetylases (HDACs) maximally at the early stage of differentiation of C2C12 cells. This led us to hypothesize that the association might be crucial to inhibition of MyoD-target proliferative genes. Chromatin immunoprecipitation analysis revealed that the CLP-1/MyoD/HDAC complex binds to the promoter of the cyclin D1 gene, which is downregulated in differentiated muscle cells. These findings suggest a novel transcriptional paradigm whereby CLP-1, in conjunction with MyoD and HDAC, acts to inhibit growth-related gene expression, a requirement for myoblasts to exit the cell cycle and transit to myotubes.


Asunto(s)
Histona Desacetilasas/metabolismo , Músculo Esquelético/patología , Proteína MioD/metabolismo , Mioblastos Esqueléticos/metabolismo , Factores de Transcripción/metabolismo , Animales , Diferenciación Celular , Línea Celular , Regulación del Desarrollo de la Expresión Génica/genética , Genes bcl-1/genética , Ratones , Mioblastos Esqueléticos/patología , Factor B de Elongación Transcripcional Positiva/metabolismo , Unión Proteica/genética , ARN Interferente Pequeño/genética , Proteínas de Unión al ARN , Factores de Transcripción/genética , Activación Transcripcional/genética
16.
BMJ Open ; 12(9): e061519, 2022 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-36691151

RESUMEN

OBJECTIVES: The aim of this study was to evaluate the quality of reporting of randomised controlled trials (RCTs) of artificial intelligence (AI) in healthcare against Consolidated Standards of Reporting Trials-AI (CONSORT-AI) guidelines. DESIGN: Systematic review. DATA SOURCES: We searched PubMed and EMBASE databases for studies reported from January 2015 to December 2021. ELIGIBILITY CRITERIA: We included RCTs reported in English that used AI as the intervention. Protocols, conference abstracts, studies on robotics and studies related to medical education were excluded. DATA EXTRACTION: The included studies were graded using the CONSORT-AI checklist, comprising 43 items, by two independent graders. The results were tabulated and descriptive statistics were reported. RESULTS: We screened 1501 potential abstracts, of which 112 full-text articles were reviewed for eligibility. A total of 42 studies were included. The number of participants ranged from 22 to 2352. Only two items of the CONSORT-AI items were fully reported in all studies. Five items were not applicable in more than 85% of the studies. Nineteen per cent (8/42) of the studies did not report more than 50% (21/43) of the CONSORT-AI checklist items. CONCLUSIONS: The quality of reporting of RCTs in AI is suboptimal. As reporting is variable in existing RCTs, caution should be exercised in interpreting the findings of some studies.


Asunto(s)
Inteligencia Artificial , Robótica , Humanos , Estándares de Referencia , Lista de Verificación , Atención a la Salud , Ensayos Clínicos Controlados Aleatorios como Asunto
17.
Cureus ; 14(1): e20876, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35145783

RESUMEN

Sympathetic ophthalmia (SO) is a rare, severe condition that typically presents as bilateral diffuse granulomatous uveitis secondary to trauma in one eye. The variability of symptoms requires that diagnosis depends heavily on the correlation of these symptoms with relevant imaging. Visualisation of characteristic nodules seen between the Bruchs membrane and the retinal pigment epithelium, and the presence of Dalén Fuchs nodules, can be diagnostic when coupled with the clinical findings. This report discusses the use of spectral domain optical coherence tomography (OCT) to indicate the presence of Dalén Fuchs nodules, which have previously not been identified on OCT in a confirmed case of SO.

18.
BMJ Case Rep ; 15(3)2022 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-35246439

RESUMEN

A female patient in early 50s presented to us several months after developing severe visual loss in her right eye. The patient was diagnosed with resolved central retinal vein occlusion (CRVO) based on the clinical picture at the time of presentation, however, retroactive evaluation of fundus imaging and further multi-disciplinary workup led to the rare diagnosis of combined central retinal artery and vein occlusion associated with antiphospholipid syndrome (APS). Only a few cases reporting retinal arterial and venous occlusions in patients with APS are found in the literature. To the best of our knowledge, no case of simultaneous CRAO and CRVO has been reported with APS. The patient was started on lifelong warfarin therapy to prevent a similar episode in the left eye. It is important to properly evaluate patients presenting with retinal vascular occlusions, as a missed diagnosis of APS can lead to recurrent and more devastating vascular events.


Asunto(s)
Síndrome Antifosfolípido , Oclusión de la Arteria Retiniana , Arteria Retiniana , Oclusión de la Vena Retiniana , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/tratamiento farmacológico , Femenino , Humanos , Retina , Oclusión de la Arteria Retiniana/complicaciones , Oclusión de la Arteria Retiniana/etiología , Oclusión de la Vena Retiniana/diagnóstico , Oclusión de la Vena Retiniana/tratamiento farmacológico , Oclusión de la Vena Retiniana/etiología
19.
Heliyon ; 8(3): e09181, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35368542

RESUMEN

n-pentane catalytic cracking was studied over a series of MFI zeolites with varying SiO2/Al2O3 ratios (30, 80, 280, 500, and 1500) using a fixed-bed reactor operated at temperature 550-650 °C. Other MFI zeolites (SiO2/Al2O3 = 280) with various crystal morphology and size (such as large crystal and nano size) were also synthesized and tested for n-pentane cracking. The effects of MFI zeolite modification with ammonia and phosphorus on its physiochemical properties and catalytic activity were investigated. Among the parent MFI zeolites, MFI (280) demonstrated high selectivity (51%) towards light olefins (C3 =/C2 = = 0.7) at 650 °C with undesired C1-C4 alkanes (38%). Surface modified MFI (280) zeolites of different crystal size and morphology showed improvement towards propylene selectivity by suppressing undesired reactions. Phosphorous-modified MFI zeolite with a large crystal size was found to improve light olefin selectivity (52.2%) with C3 =/C2 = = ∼1.3 and reduce undesired C1-C4 alkanes (8%) formation due to suppressed strong acidic sites. The characterization and evaluation results for the modified MFI (280) revealed that the incorporation of phosphorous created moderate acidic sites, which were stabilized by some non-framework aluminum species, thereby leading to suppressing the formation of undesired C1-C4 alkanes with improved light olefins selectivity.

20.
Int J Ophthalmol ; 15(12): 1966-1970, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36536979

RESUMEN

AIM: To evaluate the recently described optical coherence tomography (OCT) based classification of epiretinal membrane (ERM) and its usefulness in predicting the functional outcome. METHODS: A retrospective observational review of OCT scans of patients with the diagnosis of idiopathic ERM was carried out from January 2016 to June 2021. All consecutive images diagnosed with any stage of idiopathic ERM and fulfilled the eligibility criteria were included in the analysis. ERM was identified on OCT scans as a thin hyperreflective layer over the inner layers of retina. OCT scans of patients with ERM who underwent vitrectomy, were independently staged as per the new classification by two independent retinal surgeons to form a consensus on stage. Best corrected visual acuity (BCVA) in logMAR scale and central subfield thickness (CST) on pre- and post-operative spectral domain OCT scans were the variables noted for all patients at the time of diagnosis and at 6 and 12mo follow up visit after undergoing intervention. Partial correlation coefficient was computed between BCVA (logMAR) and CST by ERM stage adjusting by baseline measures. RESULTS: Clinical charts of 74 patients with idiopathic ERM were assessed. Clinically significant improvement in BCVA overtime was observed with significant difference in median visual acuity of patients with Stage II-IV ERM with P<0.001. The median CST of all patients with stage II-IV ERM showed similar consistent improvement with P<0.001 from baseline to 12th month. Our results showed not only gain in visual acuity but also shift from baseline to anatomical normalization of CST in stage II. We found a decrease in CST with difference of 166 µm and 151 µm in stage III and stage IV respectively. Our results remained consistent with the hypothesis of improved visual outcomes with all stages of ERM with adjusted moderate linear correlation between visual acuity and CST in stage II-IV (r>0.3). CONCLUSION: Equally significant visual outcomes of patients with ERM staged II-IV and therefore can be counselled for improved visual acuity after surgical removal of ERM with improvement up to 5 lines on Snellen's chart from the baseline.

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