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complications, infectious diseases, maternal and infant health in disasters, gender-based violence, healthcare access inequities, mental health impacts, and food security issues. Findings reveal an uneven distribution of coverage across continents, with potential language bias in English-dominated sources. Acknowledging limitations, future research directions emphasize a more inclusive approach, incorporating diverse linguistic perspectives and qualitative exploration of community experiences. The study underscores the imperative for global representation in media discourse This research explores the intricate relationship between climate change and reproductive health through an analysis of 1000 global news articles from 2018 onwards. Utilizing Latent Dirichlet Allocation (LDA), key topics in media coverage are identified, encompassing fertility challenges, pregnancy and advocates for comprehensive, evidence-based strategies to address the complex interplay between climate change and reproductive health.
Cette recherche explore la relation complexe entre le changement climatique et la santé reproductive à travers une analyse de 1 000 articles de presse mondiaux à partir de 2018. Grâce à l'allocation de Dirichlet latente (LDA), des sujets clés de la couverture médiatique sont identifiés, englobant les problèmes de fertilité, les complications de la grossesse, les maladies infectieuses, la santé maternelle et infantile en cas de catastrophe, la violence sexiste, les inégalités d'accès aux soins de santé, les impacts sur la santé mentale et les problèmes de sécurité alimentaire. . Les résultats révèlent une répartition inégale de la couverture à travers les continents, avec un biais linguistique potentiel dans les sources à dominante anglaise. Reconnaissant les limites, les futures orientations de recherche mettent l'accent sur une approche plus inclusive, intégrant diverses perspectives linguistiques et une exploration qualitative des expériences communautaires. L'étude souligne l'impératif d'une représentation mondiale dans le discours médiatique et préconise des stratégies globales et fondées sur des preuves pour aborder l'interaction complexe entre le changement climatique et la santé reproductive.
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Cambio Climático , Periodismo , Salud Reproductiva , Humanos , Femenino , EmbarazoRESUMEN
INTRODUCTION: Advanced liver disease or cirrhosis is associated with an increased risk of infections; however, the impact of high pretransplant model for end-stage liver disease (MELD) score on cytomegalovirus (CMV) viremia after liver transplantation is unknown. METHODS: This single-center, retrospective, cohort study evaluated CMV high-risk (CMV immunoglobulin G D+/R-) liver transplant recipients who received valganciclovir prophylaxis for 3 months between 2009 and 2019. Patients were stratified by pretransplant MELD score of <35 (low MELD) and ≥35 (high MELD). The primary outcome was 12-month CMV viremia, and secondary outcomes included CMV resistance and tissue invasive disease, mortality, biopsy-proven acute rejection (BPAR), leukopenia, and thrombocytopenia. Multivariable Cox proportional-hazards modeling was used to assess the association of MELD score with the time to CMV viremia. RESULTS: There were 162 and 79 patients in the low and high MELD groups, respectively. Pretransplant MELD score ≥35 was associated with an increased risk of CMV viremia (hazard ratio [HR] 1.73; confidence interval 1.06-2.82, p = .03). CMV viremia occurred at 162 ± 61 days in the low MELD group and 139 ± 62 days in the high MELD group. Although BPAR occurred early at 30 days (13-59) in the low-MELD group and at 18 days (11-66) in the high-MELD group (p = .56), BPAR was not associated with an increased risk of CMV viremia (HR 1.55 [0.93-2.60], p = .1). DISCUSSION: MELD scores ≥35 were associated with an increased hazards of CMV viremia. In liver transplant recipients with MELD scores ≥35 who are CMV high-risk, additional CMV intervention may be warranted.
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Infecciones por Citomegalovirus , Enfermedad Hepática en Estado Terminal , Trasplante de Hígado , Trombocitopenia , Humanos , Antivirales/uso terapéutico , Trasplante de Hígado/efectos adversos , Viremia/tratamiento farmacológico , Estudios Retrospectivos , Estudios de Cohortes , Enfermedad Hepática en Estado Terminal/complicaciones , Índice de Severidad de la Enfermedad , Infecciones por Citomegalovirus/prevención & control , Trombocitopenia/complicaciones , Trombocitopenia/tratamiento farmacológico , Ganciclovir/uso terapéuticoRESUMEN
BACKGROUND: Adverse childhood experiences (ACEs) increases vulnerability to externalising disorders such as substance misuse. The study aims to determine the prevalence of ACEs and its association with substance misuse. METHODS: Data from the Consortium on Vulnerability to Externalising Disorders and Addictions (cVEDA) in India was used (n = 9010). ACEs were evaluated using the World Health Organisation (WHO) Adverse Childhood Experiences International Questionnaire whilst substance misuse was assessed using the WHO Alcohol, Smoking and Substance Involvement Screening Test. A random-effects, two-stage individual patient data meta-analysis explained the associations between ACEs and substance misuse with adjustments for confounders such as sex and family structure. RESULTS: 1 in 2 participants reported child maltreatment ACEs and family level ACEs. Except for sexual abuse, males report more of every individual childhood adversity and are more likely to report misusing substances compared with females (87.3% vs. 12.7%). In adolescents, family level ACEs (adj OR 4.2, 95% CI 1.5-11.7) and collective level ACEs (adj OR 6.6, 95% CI 1.4-31.1) show associations with substance misuse whilst in young adults, child level ACEs such as maltreatment show similar strong associations (adj OR 2.0, 95% CI 1.1-3.5). CONCLUSION: ACEs such as abuse and domestic violence are strongly associated with substance misuse, most commonly tobacco, in adolescent and young adult males in India. The results suggest enhancing current ACE resilience programmes and 'trauma-informed' approaches to tackling longer-term impact of ACEs in India. FUNDING: Newton Bhabha Grant jointly funded by the Medical Research Council, UK (MR/N000390/1) and the Indian Council of Medical Research (ICMR/MRC-UK/3/M/2015-NCD-I).
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Experiencias Adversas de la Infancia , Maltrato a los Niños , Violencia Doméstica , Trastornos Relacionados con Sustancias , Adolescente , Niño , Estudios de Cohortes , Femenino , Humanos , Masculino , Trastornos Relacionados con Sustancias/epidemiologíaRESUMEN
BACKGROUND: Elderly patients are the fastest growing population requiring renal replacement therapy. As previous studies have shown a survival benefit of kidney transplantation compared to dialysis for end-stage renal disease, we sought to evaluate if this survival benefit extends to octogenarians. METHODS: This was a single-center retrospective cohort study of renal allograft recipients ≥80 years transplanted from 1999 to 2014 who were compared to patients listed during the same period that did not proceed to transplantation. A secondary matched group was selected from the UNOS transplant waitlist database. The primary outcome was patient survival. Secondary outcomes included graft survival and rejection incidence. RESULTS: Thirty-three transplanted patients were compared to 71 patients waitlisted at our center and 66 patients from the UNOS database. Patients in the study group were transplanted 20.8 ± 16.1 months after listing. Patient survival was 87.8% at 6 months and 1 year and 71.4% at 3 years. Kidney transplantation was associated with a significant decrease in the risk of death after listing (HR: 0.22, CI: 0.11-0.45, P < .001). CONCLUSION: With escalating life expectancy, kidney transplantation is a suitable treatment option in eligible octogenarians.
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Fallo Renal Crónico , Trasplante de Riñón , Anciano , Anciano de 80 o más Años , Rechazo de Injerto/etiología , Supervivencia de Injerto , Humanos , Fallo Renal Crónico/cirugía , Diálisis Renal , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
PURPOSE: Peritumoural brain zone (PT) of glioblastoma (GBM) is the area where tumour recurrence is often observed. We aimed to identify differentially regulated genes between tumour core (TC) and PT to understand the underlying molecular characteristics of infiltrating tumour cells in PT. METHODS: 17 each histologically characterised TC and PT tissues of GBM along with eight control tissues were subjected to cDNA Microarray. PT tissues contained 25-30% infiltrating tumour cells. Data was analysed using R Bioconductor software. Shortlisted genes were validated using qRT-PCR. Expression of one selected candidate gene, PDZ Binding Kinase (PBK) was correlated with patient survival, tumour recurrence and functionally characterized in vitro using gene knock-down approach. RESULTS: Unsupervised hierarchical clustering showed that TC and PT have distinct gene expression profiles compared to controls. Further, comparing TC with PT, we observed a significant overlap in gene expression profile in both, despite PT having fewer infiltrating tumour cells. qRT-PCR for 13 selected genes validated the microarray data. Expression of PBK was higher in PT as compared to TC and recurrent when compared to newly diagnosed GBM tumours. PBK knock-down showed a significant reduction in cell proliferation, migration and invasion with increase in sensitivity to radiation and Temozolomide treatment. CONCLUSIONS: We show that several genes of TC are expressed even in PT contributing to the vulnerability of PT for tumour recurrence. PBK is identified as a novel gene up-regulated in PT of GBM with a strong role in conferring aggressiveness, including radio-chemoresistance, thus contributing to recurrence in GBM tumours.
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Neoplasias Encefálicas/enzimología , Regulación Neoplásica de la Expresión Génica , Glioblastoma/enzimología , Quinasas de Proteína Quinasa Activadas por Mitógenos/genética , Recurrencia Local de Neoplasia/enzimología , Transcriptoma , Biomarcadores de Tumor/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Movimiento Celular , Proliferación Celular , Células Cultivadas , Glioblastoma/diagnóstico , Glioblastoma/genética , Humanos , Invasividad Neoplásica , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/genética , Regulación hacia ArribaRESUMEN
BACKGROUND: Cytomegalovirus (CMV) outcomes with valganciclovir prophylaxis in renal transplant recipients experiencing delayed graft function (DGF) are unclear. METHODS: This single center, retrospective, cohort study of CMV high-risk (D+/R- with alemtuzumab induction) deceased donor renal transplant recipients receiving valganciclovir prophylaxis assessed CMV outcomes in patients experiencing DGF (n = 72) versus those with immediate graft function (IGF; n = 66). RESULTS: Cytomegalovirus viremia by 12 months occurred at similar rates in the IGF and DGF groups (30.3% vs 26.4%, respectively, P = 0.71) with 89.7% (35/39) of all cases classified as CMV disease. The median time to CMV viremia post transplant was day 141 and 138 in the IGF and DGF groups, respectively (P = 0.30). The incidence of biopsy-proven acute rejection (BPAR) was higher in the DGF group (18.1% vs 4.6%, P = 0.02) with BPAR preceding CMV in only 1 patient. There was no significant difference in graft loss (1.5% vs 4.2%, P = 0.62) or patient survival (98.5% vs 95.8%, P = 0.62) at 1 year between the IGF and DGF groups, respectively. CONCLUSION: Valganciclovir prophylaxis in patients experiencing DGF yielded similar CMV outcomes up to 1-year post transplant when compared to use in patients with IGF.
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Antivirales/administración & dosificación , Funcionamiento Retardado del Injerto , Rechazo de Injerto/prevención & control , Trasplante de Riñón/efectos adversos , Receptores de Trasplantes , Valganciclovir/administración & dosificación , Adulto , Infecciones por Citomegalovirus/virología , Registros Electrónicos de Salud , Femenino , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , ViremiaRESUMEN
AIM: This study was undertaken to address the epidemiological characteristics, operative details, and surgical outcome of peripheral nerve injuries in children treated in a tertiary hospital in India (NIMHANS, Bangalore). MATERIALS AND METHODS: This is a retrospective study of epidemiology, operative findings, and surgical outcomes over the period of 2000-2016. Our series includes 102 children with peripheral nerve injuries of various causes. RESULTS: Intramuscular injections were the most common cause (52.9%), followed by entrapment (15.6%). The most common nerve involved was the sciatic nerve (54.9%), followed by the common peroneal nerve (13.7%), the ulnar nerve (10.8%), and the radial nerve (10.8%). Perineural adhesion was the most common intraoperative finding (74.5%), followed by a neuroma in continuity (14.7%) and gap (10.8%). Most of the children with peripheral adhesion underwent external and internal neurolysis (75.5%). Follow-up was available for 67 children. The median follow-up period was 7 months (range 3-36). The outcome was assessed according to MRC grading. Favorable functional improvement was noted in 76.1% of the children. Age less than 10 years (p = 0. 06), injury before 6 months (p = 0.03), and MRC motor grade (<3) (p = 0. 01) were positive predictive factors related to the final outcome. CONCLUSION: Early surgical intervention, age less than 10 years, and incomplete motor palsy were the best predictors of a superior functional outcome. This study can serve as a guide to determine the epidemiology, duration of intervention, and surgical outcome of traumatic peripheral nerve injuries in the pediatric population.
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Procedimientos Neuroquirúrgicos , Traumatismos de los Nervios Periféricos/epidemiología , Traumatismos de los Nervios Periféricos/cirugía , Resultado del Tratamiento , Niño , Femenino , Hospitales , Humanos , India , Masculino , Estudios Retrospectivos , Nervio Ciático , Factores de TiempoRESUMEN
BACKGROUND AND PURPOSE: The role of inheritance in ascertaining susceptibility to epilepsy is well established, although the pathogenetic mechanisms are still not very clear. Interviewing for a positive family history is a popular epidemiological tool in the understanding of this susceptibility. Our aim was to visualize and localize network abnormalities that could be associated with a positive family history in a group of patients with hot water epilepsy (HWE) using resting-state functional magnetic resonance imaging (rsfMRI). METHODS: Graph theory analysis of rsfMRI (clustering coefficient γ; path length λ; small worldness σ) in probands with a positive family history of epilepsy (FHE+, 25) were compared with probands without FHE (FHE-, 33). Whether a closer biological relationship was associated with a higher likelihood of network abnormalities was also ascertained. RESULTS: A positive family history of epilepsy had decreased γ, increased λ and decreased σ in bilateral temporofrontal regions compared to FHE- (false discovery rate corrected P ≤ 0.0062). These changes were more pronounced in probands having first degree relatives and siblings with epilepsy. Probands with multiple types of epilepsy in the family showed decreased σ in comparison to only HWE in the family. CONCLUSION: Graph theory analysis of the rsfMRI can be used to understand the neurobiology of diseases like genetic susceptibility in HWE. Reduced small worldness, proportional to the degree of relationship, is consistent with the current understanding that disease severity is higher in closer biological relations.
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Encéfalo/diagnóstico por imagen , Epilepsia/diagnóstico por imagen , Red Nerviosa/diagnóstico por imagen , Adolescente , Adulto , Niño , Conectoma , Familia , Femenino , Neuroimagen Funcional , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Hermanos , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Writer's cramp (WC) is a focal task-specific dystonia of the hand which is increasingly being accepted as a network disorder. Non-invasive cortical stimulation using repetitive transcranial magnetic stimulation (rTMS) has produced therapeutic benefits in some of these patients. This study aimed to visualize the motor network abnormalities in WC and also its rTMS induced modulations using resting state functional magnetic resonance imaging (rsfMRI). METHODS: Nineteen patients with right-sided WC and 20 matched healthy controls (HCs) were prospectively evaluated. All patients underwent a single session of rTMS and rsfMRI was acquired before (R1) and after (R2) rTMS. Seed-based functional connectivity analysis of several regions in the motor network was performed for HCs, R1 and R2 using SPM8 software. Thresholded (P < 0.05, false discovery rate corrected) group level mean correlation maps were used to derive significantly connected region of interest pairs. RESULTS: Writer's cramp showed a significant reduction in resting state functional connectivity in comparison with HCs involving the left cerebellum, thalamus, globus pallidus, putamen, bilateral supplementary motor area, right medial prefrontal lobe and right post central gyrus. After rTMS there was a significant increase in the contralateral resting state functional connectivity through the left thalamus-right globus pallidus-right thalamus-right prefrontal lobe network loop. CONCLUSIONS: It is concluded that WC is a network disorder with widespread dysfunction much larger than clinically evident and changes induced by rTMS probably act through subcortical and trans-hemispheric unaffected connections. Longitudinal studies with therapeutic rTMS will be required to ascertain whether such information could be used to select patients prior to rTMS therapy.
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Encéfalo/fisiopatología , Conectoma/métodos , Trastornos Distónicos/terapia , Mano/fisiopatología , Red Nerviosa/fisiopatología , Estimulación Magnética Transcraneal/métodos , Adulto , Trastornos Distónicos/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: We studied the MRI findings in 16 patients with Rasmussen's encephalitis (RE), further analysed serial MRI changes in 11 of them and correlated it with clinical features. METHODOLOGY: The diagnosis of RE was based on the European consensus statement (Brain, 128, 2005, 454). Details related to demographical, clinical, MRI observations were analysed. RESULTS: Forty MRIs of brain of 16 patients were reviewed. Eleven patients had undergone serial brain MRIs ranging from two to five occasions. All the patients had unihemispheric focal cortical atrophy, predominantly in the perisylvian region (n = 13). Other features were white matter signal changes (n = 14), and ipsilateral caudate (n = 6) and putamen (n = 4) atrophy. Signal alterations in putamen and caudate were noted in four each. In all the 11 patients with serial MRI, there was progression of cerebral atrophy and a trend towards increase in MRI staging. The MRI signal changes remained same in five patients, resolved in three patients, differential change in two patients and increased in one patient. Diffusion-weighted imaging showed facilitated diffusion (n = 5), and MR spectroscopy showed reduced N-acetyl-aspartate and elevated lactate (n = 2). CONCLUSIONS: Pattern recognition of MRI findings and the changes in serial MRI might serve as a surrogate marker of disease viz. unihemispheric progressive focal cortical atrophy and signal changes predominantly in the perisylvian distribution and caudate followed by putamen involvement. This might assist in understanding and monitoring of the disease progression.
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Encefalitis/patología , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética , Adolescente , Adulto , Atrofia/patología , Encéfalo/patología , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
PURPOSE: We describe the clinical, neuroimaging and pathological features and therapeutic outcome in a large cohort of 39 patients with tumefactive demyelination. MATERIALS AND METHODS: A retrospective audit of 39 patients with 'tumefactive demyelination' was performed. The demographic, clinical, MR imaging and pathological details were reviewed. RESULTS: The clinical course was monophasic (n = 22) or relapsing-remitting (n = 17). Common neurological manifestations at presentation included hemiparesis - 27; ataxia - 11; vomiting - 10; headache -9; ophthalmoplegia - 7; seizure - 5; impaired vision - 4; aphasia - 4; visual field defects - 3; papilloedema - 5; extrapyramidal - 5; intellectual decline - 5; behavioural disturbances - 3; altered sensorium - 5. MRI revealed fronto-parietal lesions, which were isolated in 14 (36%) patients. Moderate perilesional oedema and/or mass effect was noted in 12 (30.8%) patients. Post-contrast MR sequences revealed partial ring enhancement in 15, complete ring in seven, patchy enhancement in six, uniform enhancement in two and lack of enhancement in nine cases. Clinical and MR characteristics did not help distinguish between monophasic and relapsing-remitting subgroups. In the monophasic group, 53.8% had complete recovery, while 38.5% had partial improvement (follow-up duration, 8.31 ± 9.3 months). In the relapsing-remitting subgroup, the median time to relapse was 4 months (n = 12, follow-up, 37.8 ± 39.4 months). Patients with monophasic course or single relapse received steroids. Patients with more than one relapse received cyclophosphamide (2), mycophenolate (1), azathioprine (1) or methotrexate (1). CONCLUSIONS: A high proportion of cases of tumefactive demyelination follow a relapsing course, thus necessitating a long-term follow-up. MRI, although helpful in diagnosis, does not predict monophasic or relapsing-remitting course. Guidelines for the management of acute episodes and prevention of relapses are required.
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Enfermedades Desmielinizantes/patología , Enfermedades Desmielinizantes/terapia , Adolescente , Adulto , Anciano , Encéfalo/patología , Niño , Preescolar , Estudios de Cohortes , Enfermedades Desmielinizantes/complicaciones , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Recurrencia , Factores de Riesgo , Médula Espinal/patología , Resultado del Tratamiento , Adulto JovenRESUMEN
INTRODUCTION: The clinical and MR imaging features of neurosyphilis are highly varied. In this study, we describe the spectrum of the imaging findings in patients with neurosyphilis. METHODS: The MR imaging observations of 35 patients diagnosed to have neurosyphilis on the basis of cerebrospinal fluid reactive for the Venereal Disease Research Laboratory test were reviewed. RESULTS: All the 35 patients, including four with human immunodeficiency virus coinfection, met the CDC diagnostic criteria for neurosyphilis. Patients were classified into three groups: (1) neuropsychiatric, (2) meningovascular, and (3) myelopathic, based on the dominant clinical manifestations. Fourteen patients with neuropsychiatric manifestations showed diffuse cerebral atrophy (14), parenchymal signal changes in the mesial temporal region (2) and temporal and basifrontal regions (1), infarcts (3), and nonspecific white matter changes (3). Eleven patients with meningovascular form showed infarcts (6), diffuse cerebral atrophy (3), signal changes in the mesial temporal region (3), sulcal exudates (1), progressive multifocal leukoencephalopathy (1), and a mass surrounding the carotid sheath (1). Spine imaging in ten patients with myelopathy showed long-segment signal changes (5), contrast enhancement (2), and dorsal column involvement (2). Three of these patients had normal spinal study. Six patients in the myelopathic group also underwent brain MRI that showed signal changes in the temporal region (2) and frontal region (1), multiple infarcts (1), and enhancing hypothalami (1). Three patients had normal study. CONCLUSION: MRI abnormalities in neurosyphilis are protean and mimic of many other neurological disorders and thus require a high index of suspicion to reduce diagnostic omissions.
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Encéfalo/patología , Imagen por Resonancia Magnética/métodos , Neurosífilis/patología , Médula Espinal/patología , Centros Médicos Académicos , Adulto , Femenino , Humanos , Masculino , Fenotipo , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estadística como Asunto , Centros de Atención TerciariaRESUMEN
Background: Direct-acting antivirals for the treatment of hepatitis C virus (HCV) have improved outcomes in liver transplant recipients (LTRs). However, the timing of HCV treatment and approach to treating rejection have not been well described. Additionally, pharmacists' roles in these comprehensive areas have not been investigated. Methods: This single-center, retrospective, cohort review compared 1-year graft and patient survival between HCV-positive and HCV-negative LTRs. Secondary endpoints included 1-year rejection rates, HCV sustained virologic response and time to HCV treatment. Results: Ninety-two HCV Nucleic Acid Amplification Test (NAT)-positive LTRs were matched 1:1 to HCV-seronegative LTRs. One-year graft and patient survival were similar between groups. HCV-positive LTRs were more likely to experience biopsy-proven acute rejection (BPAR), and despite treatment with pulse steroids, there was no impact on graft survival or occurrence of fibrosing cholestatic hepatitis (FCH). Time to HCV treatment was 5.4-6.4 months post-transplant, with no treatment failures or impact on graft or patient survival. Conclusions: No difference was seen in graft survival at 1 year between HCV-positive and HCV-seronegative LTRs. Delayed time to treatment of HCV and treatment of rejections in the HCV-positive cohort did not impact outcomes. However, pharmacist-driven protocols could ensure more efficient initiation of HCV treatment in the future.
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Hepatitis C Crónica , Hepatitis C , Trasplante de Hígado , Humanos , Hepacivirus , Tiempo de Tratamiento , Antivirales/uso terapéutico , Estudios Retrospectivos , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Rechazo de InjertoRESUMEN
Proteomics aspires to elucidate the functions of all proteins. Protein microarrays provide an important step by enabling high-throughput studies of displayed proteins. However, many functional assays of proteins include untethered intermediates or products, which could frustrate the use of planar arrays at very high densities because of diffusion to neighboring features. The nucleic acid programmable protein array (NAPPA) is a robust in situ synthesis method for producing functional proteins just-in-time, which includes steps with diffusible intermediates. We determined that diffusion of expressed proteins led to cross-binding at neighboring spots at very high densities with reduced interspot spacing. To address this limitation, we have developed an innovative platform using photolithographically etched discrete silicon nanowells and used NAPPA as a test case. This arrested protein diffusion and cross-binding. We present confined high density protein expression and display, as well as functional protein-protein interactions, in 8000 nanowell arrays. This is the highest density of individual proteins in nanovessels demonstrated on a single slide. We further present proof of principle results on ultrahigh density protein arrays capable of up to 24000 nanowells on a single slide.
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Dispositivos Laboratorio en un Chip , Análisis por Matrices de Proteínas/instrumentación , Difusión , Humanos , Biosíntesis de Proteínas , Mapeo de Interacción de Proteínas , Proteoma/biosíntesis , Proteoma/genética , Proteómica , Silicio/químicaRESUMEN
Though many aspects of contact printing have been explored extensively since its invention, there are still hurdles to overcome for multilayer printing in the nanometer regime. Here we report on an aligned nanocontact printing (nCP) system that has demonstrated a sub-100 nm alignment capability by means of moiré fringes and microspacers. To address issues in the stamp inking, we have devised a microfluidic apparatus based on the gradient capillary force for transport of ink solutions. The nCP system has been tested by printing nucleoside phosphoramidites on a nanopillar arrayed substrate. Although the nCP system was designed primarily for use in the fabrication of high density DNA nanoarrays, it has the potential to be applied to other fields of nanotechnology for nanoscale patterning.
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Nanopartículas/química , Nanotecnología/métodos , Tamaño de la Partícula , Fluorescencia , Tinta , Nanopartículas/ultraestructura , Nanotecnología/instrumentación , Compuestos Organofosforados/química , Dióxido de Silicio/químicaRESUMEN
We report two patients manifesting with involvement of central and peripheral nervous system with brain magnetic resonance imaging (MRI) changes and pathological features of neuropathy possibly due to harmful and chronic use of various nitroimidazole group of medications for recurrent diarrheal illness. Patient 1, a 21-year-old man with obsessive-compulsive disorder, impulsive behavior and harmful use of substance (tinidazole), had developed encephalopathy and biopsy-proven neuropathy with partial remission. The MRI of brain showed involvement of bilateral caudate, lentiform and dentate nuclei, and splenium, with contrast enhancement of the caudate and putaminal lesions and restricted diffusion of the splenial lesion. Patient 2 was a 50-year-old woman with irritable bowel syndrome and was on harmful use of tinidazole and metronidazole. She manifested with encephalopathy, ataxia, and neuropathy. Her MRI of brain revealed involvement of bilateral putamen, dentate nuclei and periventricular white matter with restricted diffusion. Sural nerve biopsy revealed evidence of vasculitic neuropathy. At follow-up, there was definite, though incomplete, recovery in both the patients. The MRI alterations improved completely in patient 2 and substantially in patient 1. Increasing awareness among the physicians may enable early recognition of potentially reversible neurotoxicity and avoid unwarranted prescription of such medications.
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Síndromes de Neurotoxicidad , Nitroimidazoles/efectos adversos , Femenino , Humanos , Síndrome del Colon Irritable/tratamiento farmacológico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuroimagen/métodos , Síndromes de Neurotoxicidad/diagnóstico , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/patología , Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Nervios Periféricos/patología , Adulto JovenRESUMEN
OBJECTIVES: Maxillary gingival recessions can be managed by both semilunar coronally repositioned flap (SLCRF) and coronally advanced flap (CAF). The objective of this study was to compare SLRCF and CAF in terms of wound healing and periodontal parameters in the presence of magnification. MATERIALS AND METHODS: Thirty patients with Miller's class I gingival recession in maxillary anteriors and premolars were assigned to 2 groups including SLCRF and CAF. All procedures were performed using 2.5× magnifying loupes. Wound healing and periodontal clinical parameters were assessed at baseline and at 2nd, 4th, 8th and 12th week. RESULTS: No significant difference was observed in wound healing and mean percentage root coverage in both the groups at 12th week (p > 0.05). However, SLCRF showed a statistically significant reduction in percentage of root coverage (PRC) at 12th week compared to 2nd week (p < 0.05). A significant gain in Clinical attachment level, width of keratinised tissue and a significant reduction in Recession Depth and Probing Depth were seen in both the groups at 12th week. CONCLUSION: Within the limitation of this study, both techniques resulted in similar wound healing at 12th week with the use of magnification. CAF provided more root coverage compared to SLCRF technique in the maxillary class I gingival recession defects.
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INTRODUCTION: Pretransplant cardiovascular risk may be amplified after renal transplant, but little is known about its impact on graft outcomes. RESEARCH QUESTION: The purpose of this study was to determine if pretransplant cardiovascular risk was associated with graft outcomes. DESIGN: This retrospective study included deceased-donor renal transplant recipients from 2010-2015. Atherosclerotic cardiovascular disease risk for patients without prior disease was calculated and patients were categorized into high (score >20%), intermediate (7.5-20%), and low risk (<7.5%). Patients with and without prior cardiovascular disease were also compared. The main endpoint was graft failure at 3-years post-transplant. Other outcomes included major adverse cardiovascular events, biopsy-proven rejection, and mortality. RESULTS: In patients without prior atherosclerotic cardiovascular disease (N = 115), graft failure rates (4.5% vs 11.3% vs 12.5%; (P = 0.64) and major adverse cardiovascular events (9.1% vs 13.2% vs 5.0%; P = 0.52) were similar in the high, intermediate, and low risk groups. In those with prior disease (N = 220), rates of primary nonfunction (6.8% vs 1.7%; P = 0.04), major adverse cardiovascular events (7.3% vs 2.6%; P = 0.01), and heart failure (10.9% vs 3.5%; P = 0.02) were higher than those without cardiovascular; rates of major adverse cardiovascular events and heart failure were insignificant after adjusting for age, gender, and race. Other outcomes were not different. Outcomes did not differ based on pretransplant cardiovascular risk. DISCUSSION: Pretransplant atherosclerotic cardiovascular disease was associated with increased early graft failure but similar outcomes at 3-years, suggesting cardiac risk alone should not exclude transplantation.
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Enfermedades Cardiovasculares , Trasplante de Riñón , Enfermedades Cardiovasculares/epidemiología , Rechazo de Injerto/epidemiología , Supervivencia de Injerto , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
OBJECTIVE: Endothelial nitric oxide synthase gene (eNOS) polymorphism is an association with cerebral aneurysm formation, rupture, and vasospasm and plays a role in the a functional outcome. PATIENTS AND METHODS: The aim of the study was to evaluate the role of eNOS gene polymorphism and further assess the predictors of outcome in the aneurysmal subarachnoid hemorrhage (aSAH). A prospective case-control study was conducted from 2009 to 2012 among those who presented with aSAH. A serum sample was collected from aSAH patients along with age and sex-matched healthy controls. The frequency of polymorphism of eNOS gene and other factors (demographic and aneurysmal) were correlated with functional outcome at six month of follow-up. RESULTS: 100 patients with aSAH and 100 healthy controls were enrolled in the cohort. The mean age of the patient group was 51.61 years and control group was 45.81 years with a male:female ratio of 1:1.38 and 1:1.08 for patients and controls, respectively. Among all eNOS polymorphisms, 4BB (65%) 24-VNTR, TT (71%) of T-786C, and GG (71%) of G947T were the most common and frequency was similar in the control group. The occurrences of hypertension, smoking, diabetes were 32%, 37%, and 7% respectively in the patient group. Maximum patients were in WFNS grade 1 (53%) followed by 23% grade 2 and only 10% in grade 4. Fisher grade 3 (57%) was the most common followed by Fisher grade 4 (28%). Most aneurysms (97%) were in anterior circulation. 83% of the aneurysms were clipped and 10% underwent coiling. Size-wise most of the aneurysms were in the middle group (6-9 mm) followed by bigger group (>10 mm) (37%); only 6% aneurysms were in the small aneurysm (<6 mm) group. 33% of the patients had evidence of vasospasm. TT of G894T polymorphism (60%) had the highest incidence of vasospasm. Univariate analysis showed smoking (OR: 3.19, CI: 1.19-8.84, P = 0.01), 4AA (OR: 12.15, CI: 1.13-624.9, P = 0.03) variety of 24-VNTR polymorphism, CC (OR: 15.39, CI: 1.60-762.8, P = 0.01) variety of T786C polymorphism, Fisher grade 4 (OR: 3.43, CI: 1.24-9.68, P = 0.01), WFNS grade (poor vs. good) (OR: 3.42, CI: 1.17-10.12, P = 0.02), vasospasm (OR: 3.84, CI: 1.42-10.75, P = 0.006), intraoperative rupture (OR: 4.77, CI: 1.55-15.27, P = 0.004) were significantly related with unfavorable outcome at 6 months follow-up. In regression analysis, smoking (CI: 0.06-0.69, P = 0.01), Fisher grade 4 (CI: 0.09-1.00, P = 0.05), and intraoperative rupture (CI: 0.05-0.89, P = 0.03) were correlated with an unfavorable outcome at 6 months follow-up. CONCLUSION: The eNOS gene polymorphism, smoking, clinical grade (WFNS), Fisher grade, intraoperative rupture, and vasospasm play a role in functional outcome after the treatment of cerebral aneurysms.