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1.
J Pharm Pract ; : 8971900241273206, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39133075

RESUMEN

Background: Critically ill children are vulnerable to acute kidney injury (AKI) and are often exposed to nephrotoxic medications. Objectives: We aimed to investigate the association between nephrotoxic medications and the risk of AKI in critically ill children admitted to our paediatric intensive care unit (PICU). Methods: Patients aged > 1 month to ≤18 years old were prospectively recruited from 6/2020 to 6/2021. The medication records from 14 days prior to PICU admission to PICU discharge were reviewed. Medication-exposure intensity was defined as the number of concomitant nephrotoxic medications. The relative risk (RR) of nephrotoxic medication exposure indices and other potential predictors for AKI development were determined. Results: Altogether 253 episodes of admissions (median [IQR] age of 4.9 [9.6] years) were enrolled. The AKI incidence was 41.9% and 69.2% of the patients were exposed to ≥1 of the 47 nephrotoxic medications. The total nephrotoxic medication dose (RR: 1.01 [1.00, 1.02]) and medication-exposure intensity (RR: 1.381 [1.101, 1.732]) were significantly associated with AKI development. The risk of AKI increased when the medication-exposure intensity was ≥4 (RR: 3.687 (1.320, 10.301)). During their PICU stay, children with AKI received a higher number (P < .01), total dose (P < .01) and medication exposure intensity (P < .01) of nephrotoxic medications. Children with AKI who received nephrotoxic medications were more likely to have a persistently higher peak-to-baseline ratio (P = .046). Conclusion: Nephrotoxic medication exposure significantly increased the risk of AKI development among critically ill children. The use of nephrotoxic medications among critically ill children at risk for AKI should be monitored frequently.

2.
Life Sci Alliance ; 6(11)2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37722727

RESUMEN

High-quality, straightforward single-cell RNA sequencing (RNA-seq) with spatial resolution remains challenging. Here, we developed DRaqL (direct RNA recovery and quenching for laser capture microdissection), an experimental approach for efficient cell lysis of tissue sections, directly applicable to cDNA amplification. Single-cell RNA-seq combined with DRaqL allowed transcriptomic profiling from alcohol-fixed sections with efficiency comparable with that of profiling from freshly dissociated cells, together with effective exon-exon junction profiling. The combination of DRaqL with protease treatment enabled robust and efficient single-cell transcriptome analysis from formalin-fixed tissue sections. Applying this method to mouse ovarian sections, we were able to predict the transcriptome of oocytes by their size and identified an anomaly in the size-transcriptome relationship relevant to growth retardation of oocytes, in addition to detecting oocyte-specific splice isoforms. Furthermore, we identified differentially expressed genes in granulosa cells in association with their proximity to the oocytes, suggesting distinct epigenetic regulations and cell-cycle activities governing the germ-soma relationship. Thus, DRaqL is a versatile, efficient approach for high-quality single-cell RNA-seq from tissue sections, thereby revealing histological heterogeneity in folliculogenic transcriptome.


Asunto(s)
Ovario , Transcriptoma , Femenino , Animales , Ratones , Transcriptoma/genética , Perfilación de la Expresión Génica , Oocitos , Ciclo Celular
3.
Angew Chem Int Ed Engl ; 62(36): e202307424, 2023 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-37358307

RESUMEN

An efficient synthesis of cyclohexenes has been achieved from easily accessible tetrahydropyrans via a tandem 1,5-hydride shift-aldol condensation. We discovered that readily available aluminium reagents, e.g. Al2 O3 or Al(Ot Bu)3 are essential for this process, promoting the 1,5-hydride shift with complete regio- and enantiospecificity (in stark contrast to results obtained under basic conditions). The mild conditions, coupled with multiple methods available to access the tetrahydropyran starting materials makes this a versatile method with exceptional functional group tolerance. A wide range of cyclohexenes (>40 examples) have been prepared, many in enantiopure form, showing our ability to selectively install a substituent at each position around the newly forged cyclohexene ring. Experimental and computational studies revealed that aluminium serves a dual role in facilitating the hydride shift, activating both the alkoxide nucleophile and the electrophilic carbonyl group.

4.
Inflamm Regen ; 42(1): 10, 2022 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-35361277

RESUMEN

BACKGROUND: Systemic lupus erythematosus (SLE), an autoimmune disorder that damages various organ systems, is caused by a combination of genetic and environmental factors. Although germline mutations of several genes are known to cause juvenile SLE, most of the susceptibility genetic variants of adult SLE are common variants of the population, somatic mutations that cause or exacerbate SLE have not been reported. We hereby report a refractory SLE case with monocytosis accompanying somatic KRAS mutation that have been shown to cause lupus-like symptoms. CASE PRESENTATION: A 60-year-old female patient who had been diagnosed with SLE was admitted to our hospital. Although prednisolone and tacrolimus treatments had kept her thrombocytopenia and anti-DNA Ab level at bay for more than 4 years, a diagnosis of transverse myelitis was made when she became acutely ill with pleocytosis. Elevated cells (predominately monocytes), protein, IgG, and IL-6 levels were also found in the cerebrospinal fluid (CSF) of the patient. Standard pulse treatments of methylprednisolone, high-dose of prednisolone, and intravenous cyclophosphamide in combination with plasma exchange could not alleviate the refractory neural and autoimmune manifestation. Monocytosis of peripheral blood was also noted. Flow cytometric analysis revealed elevated ratio of CD14+CD16+ atypical monocytes, which excluded the possibility of chronic myelomonocytic leukemia. Lupus-like symptoms with monocytosis reminded us of Ras-associated autoimmune leukoproliferative disorder, and Sanger sequencing of KRAS and NRAS genes from the patients' peripheral blood mononuclear cells (PBMC), sorted CD3+ lymphocytes and CD14+ monocytes, and cerebrospinal fluid were performed. An activating KRAS somatic mutation was found in the patients' DNA at the time of encephalomyelitis diagnosis. CONCLUSION: Somatic mutations of some genes including KRAS may cause the refractoriness of SLE.

5.
Eur Heart J Digit Health ; 3(2): 284-295, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36713022

RESUMEN

Aims: Underutilization of guideline-directed heart failure with reduced ejection fraction (HFrEF) medications contributes to poor outcomes. Methods and results: A pilot study to evaluate the safety and efficacy of a home-based remote monitoring system for HFrEF management was performed. The system included wearable armband monitors paired with the smartphone application. An HFrEF medication titration algorithm was used to adjust medication daily. The primary endpoint was HFrEF medication utilization at 120 days. Twenty patients (60.5 ± 8.2 years, men: 85%) with HFrEF were recruited. All received angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI) at recruitment; 45% received ≥50% maximal targeted dose (MTD) with % MTD of 44.4 ± 31.7%. At baseline, 90 and 70% received beta-adrenergic blocker and mineralocorticoid receptor antagonist (MRA), 35% received ≥50% MTD beta-adrenergic blocker with % MTD of 34.1 ± 29.6%, and 25% received ≥50% MTD MRA with % MTD of 25.0 ± 19.9%. At 120 days, 70% received ≥50% MTD ACEI/ARB/ARNI (P = 0.110) with % MTD increased to 64.4 ± 33.5% (P = 0.060). The proportion receiving ≥50% MTD ARNI increased from 15 to 55% (P = 0.089) with % MTD ARNI increased from 20.6 ± 30.9 to 53.1 ± 39.5% (P = 0.006*). More patients received ≥50% MTD MRA (65 vs. 25%, P = 0.011*) with % MTD MRA increased from 25.0 ± 19.9 to 46.2 ± 28.8% (P = 0.009*). Ninety-five per cent of patients had reduced NT-proBNP with the percentage reduction of 26.7 ± 19.7%. Conclusion: Heart failure with reduced ejection fraction medication escalation with remote monitoring appeared feasible.

6.
Front Microbiol ; 12: 739779, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34956112

RESUMEN

Since the emergence of Middle East Respiratory Syndrome (MERS) in 2012, there have been a surge in the discovery and evolutionary studies of viruses in dromedaries. Here, we investigated a herd of nine dromedary calves from Umm Al Quwain, the United Arab Emirates that developed respiratory signs. Viral culture of the nasal swabs from the nine calves on Vero cells showed two different types of cytopathic effects (CPEs), suggesting the presence of two different viruses. Three samples showed typical CPEs of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) in Vero cells, which was confirmed by partial RdRp gene sequencing. Complete genome sequencing of the three MERS-CoV strains showed that they belonged to clade B3, most closely related to another dromedary MERS-CoV isolate previously detected in Dubai. They also showed evidence of recombination between lineages B4 and B5 in ORF1ab. Another three samples showed non-typical CPEs of MERS-CoV with cell rounding, progressive degeneration, and detachment. Electron microscopy revealed spherical viral particles with peplomers and diameter of about 170nm. High-throughput sequencing and metagenomic analysis showed that the genome organization (3'-N-P-M-F-HN-L-5') was typical of paramyxovirus. They possessed typical genome features similar to other viruses of the genus Respirovirus, including a conserved motif 323FAPGNYALSYAM336 in the N protein, RNA editing sites 5'-717AAAAAAGGG725-3', and 5'-1038AGAAGAAAGAAAGG1051-3' (mRNA sense) in the P gene with multiple polypeptides coding capacity, a nuclear localization signal sequence 245KVGRMYSVEYCKQKIEK261 in the M protein, a conserved sialic acid binding motif 252NRKSCS257 in the HN protein, conserved lengths of the leader (55nt) and trailer (51nt) sequences, total coding percentages (92.6-93.4%), gene-start (AGGANNAAAG), gene-end (NANNANNAAAAA), and trinucleotide intergenic sequences (CTT, mRNA sense). Phylogenetic analysis of their complete genomes showed that they were most closely related to bovine parainfluenza virus 3 (PIV3) genotype C strains. In the phylogenetic tree constructed using the complete L protein, the branch length between dromedary camel PIV3 (DcPIV3) and the nearest node is 0.04, which is >0.03, the definition used for species demarcation in the family Paramyxoviridae. Therefore, we show that DcPIV3 is a novel species of the genus Respirovirus that co-circulated with MERS-CoV in a dromedary herd in the Middle East.

7.
J Dermatol ; 48(7): 1044-1051, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33847003

RESUMEN

Severe digital ischemia (SDI), which presents with digital ulcers, necrosis, or gangrene, has been reported to be a rare manifestation of anti-aminoacyl transfer RNA synthetase (ARS) antibody-positive polymyositis/dermatomyositis or anti-synthetase syndrome. A retrospective study was conducted between 2009 and 2020 at our department to investigate the clinical features of anti-ARS antibody-positive patients with SDI and identify their predictors. A total of 46 patients who were positive for anti-ARS antibody were included, four of whom (8.7%) presented with SDI. The characteristics of the patients with SDI were as follows: the median age was 74 years, with 75% being female; anti-Jo-1 antibody, Raynaud's phenomenon, interstitial lung disease, and myositis were observed in two (50%), four (100%), four (100%), and three patients (75%), respectively. Next, we reviewed the literature of anti-ARS antibody-positive patients with SDI and investigated the predictors of SDI by analyzing a total of 51 patients, including the previously reported five patients with SDI. Multivariable analyses revealed that Raynaud's phenomenon and myositis independently predicted the development of SDI in patients with anti-ARS antibody. In conclusion, digital ulcers, necrosis, or gangrene seem to be more common presentations in our study, and Raynaud's phenomenon and myositis can predict the complications of SDI in anti-ARS antibody-positive patients.


Asunto(s)
Aminoacil-ARNt Sintetasas , Dermatomiositis , Miositis , Anciano , Autoanticuerpos , Femenino , Humanos , Isquemia , Masculino , Estudios Retrospectivos
8.
Sci Rep ; 11(1): 4388, 2021 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-33623096

RESUMEN

Patients infected with SARS-CoV-2 may deteriorate rapidly and therefore continuous monitoring is necessary. We conducted an observational study involving patients with mild COVID-19 to explore the potentials of wearable biosensors and machine learning-based analysis of physiology parameters to detect clinical deterioration. Thirty-four patients (median age: 32 years; male: 52.9%) with mild COVID-19 from Queen Mary Hospital were recruited. The mean National Early Warning Score 2 (NEWS2) were 0.59 ± 0.7. 1231 manual measurement of physiology parameters were performed during hospital stay (median 15 days). Physiology parameters obtained from wearable biosensors correlated well with manual measurement including pulse rate (r = 0.96, p < 0.0001) and oxygen saturation (r = 0.87, p < 0.0001). A machine learning-derived index reflecting overall health status, Biovitals Index (BI), was generated by autonomous analysis of physiology parameters, symptoms, and other medical data. Daily BI was linearly associated with respiratory tract viral load (p < 0.0001) and NEWS2 (r = 0.75, p < 0.001). BI was superior to NEWS2 in predicting clinical worsening events (sensitivity 94.1% and specificity 88.9%) and prolonged hospitalization (sensitivity 66.7% and specificity 72.7%). Wearable biosensors coupled with machine learning-derived health index allowed automated detection of clinical deterioration.


Asunto(s)
Técnicas Biosensibles/métodos , COVID-19 , Aprendizaje Automático , Dispositivos Electrónicos Vestibles , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Observacionales como Asunto , Adulto Joven
9.
Front Microbiol ; 12: 795449, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35095806

RESUMEN

Since its first discovery in 1967, human coronavirus OC43 (HCoV-OC43) has been associated with mild self-limiting upper respiratory infections worldwide. Fatal primary pneumonia due to HCoV-OC43 is not frequently described. This study describes a case of fatal primary pneumonia associated with HCoV-OC43 in a 75-year-old patient with good past health. The viral loads of the respiratory tract specimens (bronchoalveolar lavage and endotracheal aspirate) from diagnosis to death were persistently high (3.49 × 106-1.10 × 1010 copies/ml). HCoV-OC43 at a 6.46 × 103 copies/ml level was also detected from his pleural fluid 2 days before his death. Complete genome sequencing and phylogenetic analysis showed that the present HCoV-OC43 forms a distinct cluster with three other HCoV-OC43 from United States, with a bootstrap value of 100% and sharing 99.9% nucleotide identities. Pairwise genetic distance between this cluster and other HCoV-OC43 genotypes ranged from 0.27 ± 0.02% to 1.25 ± 0.01%. In contrast, the lowest pairwise genetic distance between existing HCoV-OC43 genotypes was 0.26 ± 0.02%, suggesting that this cluster constitutes a novel HCoV-OC43 genotype, which we named genotype I. Unlike genotypes D, E, F, G, and H, no recombination event was observed for this novel genotype. Structural modeling revealed that the loop with the S1/S2 cleavage site was four amino acids longer than other HCoV-OC43, making it more exposed and accessible to protease, which may have resulted in its possible hypervirulence.

10.
Int J Mol Sci ; 21(15)2020 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-32751106

RESUMEN

To control the COVID-19 pandemic and prevent its resurgence in areas preparing for a return of economic activities, a method for a rapid, simple, and inexpensive point-of-care diagnosis and mass screening is urgently needed. We developed and evaluated a one-step colorimetric reverse-transcriptional loop-mediated isothermal amplification assay (COVID-19-LAMP) for detection of SARS-CoV-2, using SARS-CoV-2 isolate and respiratory samples from patients with COVID-19 (n = 223) and other respiratory virus infections (n = 143). The assay involves simple equipment and techniques and low cost, without the need for expensive qPCR machines, and the result, indicated by color change, is easily interpreted by naked eyes. COVID-19-LAMP can detect SARS-CoV-2 RNA with detection limit of 42 copies/reaction. Of 223 respiratory samples positive for SARS-CoV-2 by qRT-PCR, 212 and 219 were positive by COVID-19-LAMP at 60 and 90 min (sensitivities of 95.07% and 98.21%) respectively, with the highest sensitivities among nasopharyngeal swabs (96.88% and 98.96%), compared to sputum/deep throat saliva samples (94.03% and 97.02%), and throat swab samples (93.33% and 98.33%). None of the 143 samples with other respiratory viruses were positive by COVID-19-LAMP, showing 100% specificity. Samples with higher viral load showed shorter detection time, some as early as 30 min. This inexpensive, highly sensitive and specific COVID-19-LAMP assay can be useful for rapid deployment as mobile diagnostic units to resource-limiting areas for point-of-care diagnosis, and for unlimited high-throughput mass screening at borders to reduce cross-regional transmission.


Asunto(s)
Betacoronavirus/genética , Colorimetría/métodos , Infecciones por Coronavirus/diagnóstico , Tamizaje Masivo/economía , Neumonía Viral/diagnóstico , ARN Viral/análisis , Betacoronavirus/aislamiento & purificación , COVID-19 , Colorimetría/economía , Infecciones por Coronavirus/virología , Humanos , Límite de Detección , Nasofaringe/virología , Técnicas de Amplificación de Ácido Nucleico/métodos , Pandemias , Neumonía Viral/virología , Sistemas de Atención de Punto , ARN Viral/metabolismo , SARS-CoV-2 , Carga Viral
11.
Asia Pac J Clin Oncol ; 16(3): 115-122, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31957344

RESUMEN

BACKGROUND/AIMS: This study compared rates of clinical trial participation and perceived adequacy of information provided prior to consent in migrant and Australian-born cancer patients, and explored factors associated with being approached and agreeing to participate. METHODS: We utilized data from a larger cross-sectional survey assessing disparities in patient-reported outcomes in Chinese, Arabic, or Greek migrant versus English-speaking Australian-born cancer patients. Participants completed a questionnaire eliciting demographic and disease details, communication challenges, whether invited and consented to a clinical trial, and if so, adequacy of information received. RESULTS: A total of 566 migrants (142 Arabic, 251 Chinese, and 173 Greek) and 270 English-speaking Australian-born patients participated. Overall, 25% were approached to participate in clinical trials, and of these, 74% consented. Migrants were significantly less likely to consent if asked to participate in clinical trials (P = .009), and fewer migrants (67.2%) reported receiving sufficient information prior to deciding on trial participation (82.1%; P = .04). Perceived understanding of the health system (odds ratio [OR] = 0.71), confidence in speaking (OR = 0.75), ability to understand English (OR = 0.80), and communicate with doctors in English (OR = 0.81) were significantly related to patients' likelihood of being approached to participate in clinical trials. Perceived understanding of the health system (OR = 0.66) was significantly associated with patients agreeing to take part in cancer clinical trials. CONCLUSIONS: Our findings identified that barriers to migrants' self-reported participation in clinical trials include perceived lack of understanding of the health system and low English proficiency. Strategies that address these barriers are needed to increase migrant patients' participation in cancer clinical trials.


Asunto(s)
Neoplasias/congénito , Neoplasias/epidemiología , Participación del Paciente/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Australia , Ensayos Clínicos como Asunto , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Migrantes , Adulto Joven
12.
PLoS One ; 14(8): e0220607, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31408473

RESUMEN

While there have been many studies using machine learning (ML) algorithms to predict process outcomes and device performance in semiconductor manufacturing, the extensively developed technology computer-aided design (TCAD) physical models should play a more significant role in conjunction with ML. While TCAD models have been effective in predicting the trends of experiments, a machine learning statistical model is more capable of predicting the anomalous effects that can be dependent on the chambers, machines, fabrication environment, and specific layouts. In this paper, we use an analytics-statistics mixed training (ASMT) approach using TCAD. Under this method, the TCAD models are incorporated into the machine learning training procedure. The mixed dataset with the experimental and TCAD results improved the prediction in terms of accuracy. With the application of ASMT to the BOSCH process, we show that the mean square error (MSE) can be effectively decreased when the analytics-statistics mixed training (ASMT) scheme is used instead of the classic neural network (NN) used in the baseline study. In this method, statistical induction and analytical deduction can be combined to increase the prediction accuracy of future intelligent semiconductor manufacturing.

13.
Body Image ; 29: 90-99, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30884385

RESUMEN

Social media allow users to play multiple roles as receivers, exhibitors, and evaluators of idealized images through photo browsing, posting, and editing. In this study, we examined the associations between adolescent girls' various types of Instagram selfie practices and their body esteem. The mediating role of appearance comparisons and the moderating role of direction of comparisons were also tested. A survey was distributed to 303 adolescent girls from three secondary schools in Singapore. Results indicated that the negative associations between participants' photo browsing and editing behaviors and body esteem were fully mediated by peer appearance comparisons. Contrarily, selfie posting had a direct and positive association with body esteem that was not mediated by peer appearance comparisons. The findings suggested that objectifying standards of beauty may permeate adolescent girls' value systems through frequent appearance comparisons on social media. When peer influence was presented in the form of appearance comparisons, it had a strong negative association with body esteem, regardless of the direction of the comparisons involved. The positive relationship between selfie posting and body esteem suggested that peer interactions may benefit adolescent girls' body image development in specific ways that warrants further inquiry.


Asunto(s)
Conducta del Adolescente/psicología , Imagen Corporal/psicología , Grupo Paritario , Autoimagen , Medios de Comunicación Sociales/estadística & datos numéricos , Adolescente , Belleza , Niño , Femenino , Humanos , Instituciones Académicas , Singapur
14.
Ann Rheum Dis ; 78(4): 509-518, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30679154

RESUMEN

OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterised by autoantibody production and widespread inflammation damaging many organs. Previous genome-wide association studies (GWASs) have revealed over 80 genetic determinants of SLE, but they collectively explain a fraction of the heritability, and only a few were proven in vivo for the involvement in SLE. We conducted a meta-analysis of SLE GWAS in the Japanese population, followed by functional analyses of a susceptibility gene with use of mutant mice. METHODS: We conducted a meta-analysis of two GWASs comprising a total of 1363 cases and 5536 controls using the 1000 Genome Project data as an imputation reference. Enrichment analyses for functional annotations were conducted. We examined Phospholipase D4 (Pld4) mutant mice to assess functional involvement of a genetic determinant. RESULTS: We found a total of 14 significant loci, which included rs2582511 in AHNAK2/PLD4 recently reported in a Chinese study and a novel locus of rs143181706 in MAMLD1 (p=7.9×10-11 and 3.7×10-8, respectively). PLD4 risk allele was associated with anti-dsDNA antibody production. Enrichment analysis of genetic signals revealed involvement of a wide range of immune-related cells and pathways. Pld4 mutant mice revealed remarkably low body weight. The mice demonstrated autoimmune phenotypes compatible with SLE, including splenomegaly and lymphadenopathy, expansion of B cells and hypersecretion of BAFF and production of autoantibodies especially anti-nuclear antibody and anti-dsDNA antibody. CONCLUSIONS: We found a novel susceptibility gene to SLE. Pld4 mutant mice revealed autoimmune phenotypes suggesting functional involvement of PLD4 with the basics of SLE.


Asunto(s)
Enfermedades Autoinmunes/genética , Exonucleasas/genética , Lupus Eritematoso Sistémico/genética , Animales , Anticuerpos Antinucleares/biosíntesis , Autoanticuerpos/biosíntesis , Enfermedades Autoinmunes/inmunología , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Inmunofenotipificación , Lupus Eritematoso Sistémico/inmunología , Masculino , Ratones Mutantes , Polimorfismo de Nucleótido Simple
15.
Ann Acad Med Singap ; 48(11): 382-385, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31960019

RESUMEN

The elderly patient presenting with an acute surgical abdomen or bowel obstruction has become a common and challenging situation. These patients bring comorbidity and frailty that necessitate appropriate risk assessment and comprehensive perioperative management. Robust communication is required between patients, families and health professions. The Australia and New Zealand Emergency Laparotomy Audit-Quality Improvement (ANZELA-QI) study is based on the United Kingdom's National Emergency Laparotomy Audit (NELA) and will gather large scale data, providing hospital-level information to enable clinicians to reduce variation in management. Successful management of the elderly laparotomy patient requires close coordination between surgeons, anaesthetists and physicians. The ANZELA-QI study will help establish the role of collaborative models of care and the need for perioperative care teams.


Asunto(s)
Abdomen Agudo/cirugía , Urgencias Médicas , Servicio de Urgencia en Hospital , Laparotomía/métodos , Mejoramiento de la Calidad , Medición de Riesgo/métodos , Abdomen Agudo/epidemiología , Anciano , Salud Global , Humanos , Incidencia , Tasa de Supervivencia/tendencias
16.
ADMET DMPK ; 7(1): 22-43, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-35350745

RESUMEN

Oseltamivir phosphate (OP, Tamiflu®) is a widely used prodrug for the treatment of influenza viral infections. Orally administered OP is rapidly hydrolyzed by the carboxylesterases in animals to oseltamivir carboxylate (OC), a potent influenza virus neuraminidase inhibitor. The goals of this study were to develop and validate a physiologically-based pharmacokinetic (PBPK) model of OP/OC in rats and humans, and to predict the internal tissue doses for OP and OC in humans after receiving OP orally. To this end, a PBPK model of OP/OC was first developed in the rat, which was then scaled up to humans by replacing the physiological and biochemical parameters with human-specific values. The proposed PBPK model consisted of an OP and an OC sub-models each containing nine first-order, flow-limited tissue/organ compartments. OP metabolism to OC was assumed to carry out mainly by hepatic carboxylesterases although extra-hepatic metabolism also occurred especially in the plasma. The PBPK model was developed and validated by experimental data from our laboratories and from the literature. The proposed PBPK model accurately predicted the pharmacokinetic behavior of OP and OC in humans and rats after receiving a single or multiple doses of OP orally or an OC dose i.v. The PBPK model was used to predict the internal tissue doses of OP and OC in a hypothetical human after receiving the recommended dose of 75 mg/kg OP b.i.d. for 6 days. Steady-state OC concentrations in the plasma and major organs such as the lung and the brain were higher than the minimum in vitro IC50 reported for H1N1 influenza virus neuraminidase, confirming OP is an effective, anti-viral agent. OP side-effects in the gastrointestinal tract and brain of humans were explainable by the tissue doses found in these organs. The PBPK model provides a quantitative tool to evaluate the relationship between an externally applied dose of OP and the internal tissue doses in humans. As such the model can be used to adjust the dose regimens for adult patients in disease states e.g., renal failure and liver damage.

17.
Endocrinology ; 159(9): 3403-3420, 2018 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-30099545

RESUMEN

Retinoic acid receptor α (RARA), a retinoic acid-dependent transcription factor, is expressed in both somatic and germ cells of the testis. Rara-null male mice with global Rara mutations displayed severely degenerated testis and infertility phenotypes. To elucidate the specific responsibility of germ cell RARA in spermatogenesis, Rara was deleted in germ cells, generating germ cell-specific Rara conditional knockout (cKO) mice. These Rara cKO animals exhibited phenotypes of quantitatively reduced epididymal sperm counts and disorganized germ cell layers in the seminiferous tubules, which worsened with aging. Abnormal tubules lacked lumen, contained vacuoles, and showed massive germ cell sloughing, all characteristics similar to those observed in Rara-null tubules. Spermatocyte chromosomal spreads revealed a novel role for germ cell RARA in modulating the integrity of synaptonemal complexes and meiotic progression. Furthermore, the initiation of spermatogenesis from spermatogonial stem cells was decreased in Rara cKO testes following busulfan treatment, supporting a role of germ cell RARA in spermatogonial proliferation. Collectively, the evidence in this study indicates that RARA produced in male germ cells has a broad spectrum of functions throughout spermatogenesis, which includes the maintenance of seminiferous epithelium organization, the integrity of the meiotic genome, and spermatogonial proliferation and differentiation. The results further suggest that germ cell RARA has dual functions: intrinsically in germ cells, balancing proliferation and differentiation of spermatogonia, and controlling genome integrity during meiosis; and extrinsically in the crosstalks with Sertoli cells, controlling the cell junctional physiology for coordinating proper spatial and temporal development of germ cells during spermatogenesis.


Asunto(s)
Meiosis/genética , Receptor alfa de Ácido Retinoico/genética , Espermatogénesis/genética , Espermatozoides/metabolismo , Animales , Diferenciación Celular/genética , Proliferación Celular/genética , Epidídimo , Células Germinativas , Uniones Intercelulares/metabolismo , Masculino , Ratones , Ratones Noqueados , Receptor alfa de Ácido Retinoico/metabolismo , Epitelio Seminífero/metabolismo , Túbulos Seminíferos/metabolismo , Células de Sertoli/metabolismo , Transducción de Señal , Recuento de Espermatozoides , Espermatocitos/crecimiento & desarrollo , Espermatocitos/metabolismo , Espermatogonias/crecimiento & desarrollo , Espermatogonias/metabolismo , Testículo
18.
J Healthc Qual ; 40(6): 336-343, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29315150

RESUMEN

OBJECTIVES: To determine the association between management standards and clinical outcomes among patients with hip fracture (HF). METHODS: Data from a prospective cohort study were linked with hospital administration data. RESULTS: In 2014 and 2015, 493 patients had surgery for HF. The proportion of patients meeting care standards ranged from 69% for surgery within 48 hours to 96% for being seen by a geriatrician. Thirty-nine per cent of patients received all the standards. The mean waiting time for surgery was 44 hours (median, 34 hours; interquartile range [IQR], 22-58 hours). The mean length of stay for patients who were alive at discharge was 17 days (median, 13 days; IQR, 6-24 days). Fifty-six patients were readmitted within 28 days of discharge (12%), and 40 patients died within 28 days of admission (8.1%). Patients who received all standards were less likely to be readmitted or die. Surgery within 48 hours and being seen by a physiotherapist were associated with a lower mortality rate. CONCLUSIONS: The management standards, collectively and in particular, assessment by a physiotherapist and surgery within 48 hours were significantly associated with better clinical outcomes.


Asunto(s)
Fracturas de Cadera/rehabilitación , Fracturas de Cadera/cirugía , Alta del Paciente/normas , Cuidados Posoperatorios/normas , Guías de Práctica Clínica como Asunto , Rehabilitación/normas , Adulto , Anciano , Anciano de 80 o más Años , Australia , Estudios de Cohortes , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Alta del Paciente/estadística & datos numéricos , Estudios Prospectivos , Rehabilitación/estadística & datos numéricos , Factores de Tiempo , Resultado del Tratamiento
19.
RSC Adv ; 8(7): 3453-3461, 2018 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-35542922

RESUMEN

Carbon nanotubes (CNTs) possesses decent optical properties and thus can be considered as a candidate for perfect absorbers due to their close-to-air refractive index and minimal extinction. However, weak absorption in porous materials, due to the low extinction coefficients, requires an inevitably thick absorption layer (∼100 µm) for the perfect opaque absorbers. Thus, the requirement of large thicknesses of CNTs prohibits them from being used as miniaturized integrated photonic devices. Here, we propose an electrophoretic deposited (EPD) CNT resonant cavity structure on tantalum (Ta) to enhance optical absorption. Efficient random light scattering along with the resonant cavity structure using Ti/SiO2 stacking enhances the absorption in our proposed EPD-CNT film while maintaining the total device thickness to <1 µm. The experiment results reveal that the absorption band covers the entire UV-VIS-NIR spectrum (λ = 0.3-2.6 µm), using resonant-cavity EPD-CNT design. The EPD deposition process is done at relatively low temperature < 120 °C. We believe that this proposal is very promising for sensing, antenna, and thermophotovoltaics (TPV), in terms of bandwidth, compactness and cost.

20.
Health Inf Manag ; 47(1): 38-45, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28745563

RESUMEN

OBJECTIVES: To examine the validity of routinely collected data in identifying hip fractures (HFs) and to identify factors associated with incorrect coding. METHOD: In a prospective cohort study between January 2014 and June 2016, HFs were identified using physician diagnosis and diagnostic imaging and were recorded in a Registry. Records of HFs in the health information exchange (HIE) were identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification/Australian Classification of Health Interventions/Australian Coding Standards codes. New HFs were estimated by episode of care, hospital admission and with an algorithm. Data from the HIE and the Registry were compared. RESULTS: The number of HFs as the principal diagnosis (PD) recorded by episode (864) was higher than by admission (743), by algorithm (711) and in the Registry (638). The sensitivity was high for all methods (90-93%) but the positive predictive value was lower for episode (68%) than for admission (80%) or algorithm (81%). The number of HFs with surgery recorded in the PD by episode (639), algorithm (630) and in the Registry (623) was similar but higher than by admission (589). The episode and algorithm methods also had higher sensitivity (91-92%) than the admission method (84%) for HFs with surgery. Factors associated with coding errors included subsequent HF, long hospital stay, intracapsular fracture, younger age, male, HF without surgery and death in hospital. CONCLUSIONS: When it is not practical to use the algorithm for regular monitoring of HFs, using PD by admission to estimate total HFs and PD by episode in combination with a procedure code to estimate HFs with surgery can produce robust estimations.


Asunto(s)
Recolección de Datos/normas , Fracturas de Cadera/epidemiología , Hospitalización , Centros de Atención Terciaria , Anciano , Anciano de 80 o más Años , Australia/epidemiología , Codificación Clínica/normas , Femenino , Intercambio de Información en Salud , Humanos , Clasificación Internacional de Enfermedades , Modelos Logísticos , Masculino , Estudios Prospectivos , Sistema de Registros
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