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1.
Int J Biol Macromol ; : 136160, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39357695

RESUMEN

Recently, the fabrication of personalized scaffolds with high accuracy has been developed through 3D printing technology. In the current study, polylactic acid/polyethylene glycol (PLA/PEG) composite scaffolds with varied weight percentages (0, 5, 10, 20 and 30 %) of bredigite nanoparticles (B) were fabricated using the 3D printing and then characterized through scanning electron microscopy and Fourier transform infra-red spectroscopy. The addition of B nanoparticles up to 20 wt% to PLA/PEG scaffold increased the compressive strength (from 7.59 to 13.84 MPa) and elastic modulus (from 142.42 to 268.33 MPa). The apatite formation ability as well as inorganic ion release in simulated body fluid were investigated for 28 days. The MG-63 cells viability and adhesion were enhanced by increasing the amount of B in the PLA/PEG scaffold and the osteogenic differentiation of the rat bone marrow mesenchymal stem cells was confirmed by alkaline phosphatase activity test and alizarin red staining. According to chorioallantoic membrane assay, the highest angiogenesis occurred around the PLA/PEG/B30 scaffold. In vivo experiments on a rat calvarial defect model demonstrated an almost complete recovery in the PLA/PEG/B30 group within 8 weeks. Based on the results, the PLA/PEG/B30 composite scaffold is proposed as an optimal scaffold to repair bone defects.

2.
Int J Biol Macromol ; 274(Pt 1): 133218, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38901512

RESUMEN

Severe bleeding has caused significant financial losses as well as a major risk to the lives and health of military and civilian populations. Under some situations, the natural coagulation mechanism of the body is unable to achieve fast hemostasis without the use of hemostatic drugs. Thus, the development of hemostatic materials and techniques is essential. Improving the quality of life and survival rate of patients and minimizing bodily damage requires fast, efficient hemostasis and prevention of bleeding. Alginate is regarded as an outstanding hemostatic polymer because of its non-immunogenicity, biodegradability, good biocompatibility, simple gelation, non-toxicity, and easy availability. This review summarizes the basics of hemostasis and emphasizes the recent developments regarding alginate-based hemostatic systems. Structural modifications and mixing with other materials have widely been used for the improvement of hemostatic characteristics of alginate and for making multifunctional medical devices that not only prevent uncontrolled bleeding but also have antibacterial characteristics, drug delivery abilities, and curing effects. This review is hoped to prepare critical insights into alginate modifications for better hemostatic properties.


Asunto(s)
Alginatos , Hemorragia , Hemostáticos , Alginatos/química , Alginatos/uso terapéutico , Hemostáticos/química , Hemostáticos/uso terapéutico , Hemostáticos/farmacología , Humanos , Hemorragia/tratamiento farmacológico , Animales , Hemostasis/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/uso terapéutico
3.
Int J Biol Macromol ; 253(Pt 6): 127249, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-37802435

RESUMEN

Skin is the largest organ of the human body, which acts as a protective barrier against pathogens. Therefore, a lot of research has been carried out on wound care and healing. Creating an ideal environment for wound healing and optimizing the local and systemic conditions of the patient play critical roles in successful wound care. Many products have been developed for improving the wound environment and providing a protected and moist area for fast healing. However, there is still high demand for new systems with high efficiency. The first generation of wound dressings merely covered the wound, while the subsequent/last generations covered it and aided in healing it in different ways. In modern wound dressings, the kind of used materials and their complexity play a crucial role in the healing process. These new systems support wound healing by lowering inflammation, exudate, slough, and bacteria. This study addresses a review of alginate/hyaluronic acid-based wound dressings developed so far as well as binary and ternary systems and their role in wound healing. Our review corroborates that these systems can open up a new horizon for wounds that do not respond to usual treatments and have a long curing period.


Asunto(s)
Alginatos , Ácido Hialurónico , Humanos , Alginatos/uso terapéutico , Cicatrización de Heridas , Vendajes , Piel/microbiología
4.
Int J Biol Macromol ; 221: 1325-1334, 2022 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-36087749

RESUMEN

One of the challenges in critical size bone defect repairing is the use of a porous degradable scaffold with appropriate properties to the host tissue. Nowadays, the three-dimensional (3D) printing method can produce custom and personalized scaffolds and overcome the problems of traditional methods by controlling the porosity and dimensions of biomaterial scaffolds. In this study, polylactic acid/polyethylene glycol (PLA/PEG) scaffolds were prepared with different PEG percentages (0, 5, 10, 15 and 20 wt%) by fused deposition modeling (FDM) to optimize printability and achieve suitable physico-mechanical properties and also enhance cellular behavior for bone tissue engineering and actually, this study complements previous studies. Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) were employed for chemical, morphological and thermal evaluations, respectively. It was shown that the adding of 20 wt% PEG to PLA 3D printed scaffolds reduced water contact angle (from 78.16 ± 3.27 to 60.00 ± 2.16), and increased surface wettability. The results also showed that the mechanical properties of the printed scaffolds were not significantly reduced by adding 5 and 10 wt% of PEG. The addition of PEG increased the degradability of scaffolds during immersion in phosphate buffer saline (PBS) solution for 8 weeks and PLA/PEG20 scaffold with 50.96 % had the highest rate of degradation. MTT assay showed that none of the studied scaffolds had cytotoxicity against MG-63 cells and increasing the PEG levels to 20 wt%, increased cell viability and adhesion and osteogenic differentiation. According to the obtained physical, mechanical and biological results, PLA/PEG scaffold printed by the FDM method can be an appropriate candidate for use in bone repair applications.


Asunto(s)
Polietilenglicoles , Ingeniería de Tejidos , Ingeniería de Tejidos/métodos , Polietilenglicoles/química , Osteogénesis , Andamios del Tejido/química , Poliésteres/química , Porosidad , Impresión Tridimensional , Ácido Láctico/química
5.
Int J Biol Macromol ; 184: 618-635, 2021 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-34166696

RESUMEN

Cancer is one of the major causes of death worldwide, and its prevalence is rising every day. New methods and materials with multifunctional tasks such as simultaneous hyperthermia treatment and drug release with minimum side effects are highly demanded. Magnetic chitosan nanocomposites can be utilized for localized tumor heating under magnetic field and have a controlled anticancer drug release due to unique functional groups of chitosan with the least complications. Combining different types of magnetic cores and engineered chitosan shells can create unique characteristics such as biocompatibility, the least toxic effects, long-term circulation in the body, controlled drug released, and the ability to carry various medicines. Recent advances in the synthesis, development, and applications of magnetic chitosan nanocomposites for hyperthermia and drug delivery are summarized in this review. The structure and different heating and drug release mechanisms of this magnetic system are discussed.


Asunto(s)
Antineoplásicos/química , Quitosano/química , Neoplasias/terapia , Antineoplásicos/farmacología , Terapia Combinada , Sistemas de Liberación de Medicamentos , Humanos , Hipertermia Inducida , Fenómenos Magnéticos , Nanocompuestos/química
6.
Psychol Med ; 51(8): 1338-1344, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-32063235

RESUMEN

BACKGROUND: Cognitive impairment is a core feature of Huntington's disease (HD), however, the onset and rate of cognitive decline is highly variable. Apathy is the most common neuropsychiatric symptom of HD, and is associated with cognitive impairment. The aim of this study was to investigate apathy as a predictor of subsequent cognitive decline over 2 years in premanifest and early HD, using a prospective, longitudinal design. METHODS: A total of 118 premanifest HD gene carriers, 111 early HD and 118 healthy control participants from the multi-centre TRACK-HD study were included. Apathy symptoms were assessed at baseline using the apathy severity rating from the Short Problem Behaviours Assessment. A composite of 12 outcome measures from nine cognitive tasks was used to assess cognitive function at baseline and after 24 months. RESULTS: In the premanifest group, after controlling for age, depression and motor signs, more apathy symptoms predicted faster cognitive decline over 2 years. In contrast, in the early HD group, more motor signs, but not apathy, predicted faster subsequent cognitive decline. In the control group, only older age predicted cognitive decline. CONCLUSIONS: Our findings indicate that in premanifest HD, apathy is a harbinger for cognitive decline. In contrast, after motor onset, in early diagnosed HD, motor symptom severity more strongly predicts the rate of cognitive decline.


Asunto(s)
Apatía , Disfunción Cognitiva , Enfermedad de Huntington , Humanos , Preescolar , Enfermedad de Huntington/genética , Enfermedad de Huntington/psicología , Estudios Prospectivos , Disfunción Cognitiva/complicaciones , Cognición
7.
J Microbiol Methods ; 179: 106089, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33184030

RESUMEN

BACKGROUND: Mycoplasma genitalium resistance to antibiotic treatments is increasing, with very limited treatment alternatives on the horizon. Surveillance via sequencing of multiple M. genitalium loci would allow: monitoring of known antibiotic resistance mutations, associations between resistance/treatment failure and specific mutations, and strain typing for epidemiological purposes. In this study we assessed the performance of a custom amplicon sequencing approach, which negates the cost of library preparation for next generation sequencing. METHODS: Fifty-two M. genitalium positive samples (cervical, vaginal, anal and rectal swabs, and urine) were used. Three regions associated with M. genitalium antibiotic resistance (23S rRNA, parC and gyrA genes) were targeted, in conjunction with a locus used for differentiation of sequence types in the mgpB gene, and findings compared to Sanger sequencing. RESULTS: Amplicon sequencing provided adequate sequence read coverage (>30×) for the majority of samples for 23S rRNA gene (96%) and mgpB (97%), parC (78%) and gyrA (75%). Single nucleotide polymorphisms (SNPs) were characterised in samples for 23S rRNA gene (94%), parC (56%) and gyrA (4%). Unlike Sanger sequencing, mixed mutations could be identified by the amplicon sequencing method, and ratios of mutation types determined. All results, with one exception, were concordant to Sanger sequence results. Sequence diversity in the mgpB region was represented by 15 sequence types, 4 being observed in multiple samples. CONCLUSIONS: We have demonstrated the utility of this custom amplicon sequencing approach for generating highly informative datasets with the capacity to identify and determine ratios of mixed sequences. The use of this customisable amplicon sequencing method enables cost effective, scalable amplicon sequencing of multiple target regions of interest in M. genitalium.


Asunto(s)
Girasa de ADN/genética , Topoisomerasa de ADN IV/genética , Farmacorresistencia Bacteriana/genética , Mycoplasma genitalium/efectos de los fármacos , Mycoplasma genitalium/genética , ARN Ribosómico 23S/genética , Secuencia de Aminoácidos/genética , Secuencia de Bases , ADN Bacteriano/genética , Humanos , Polimorfismo de Nucleótido Simple/genética , Análisis de Secuencia de ADN
8.
Clin Microbiol Infect ; 26(6): 748-752, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31654795

RESUMEN

OBJECTIVES: To compare the performance of dual immunostaining of p16INK4a and Ki-67 proteins performed on self-collected vaginal specimens and clinician-collected cervical specimens, and to evaluate the performance of this technique in predicting high-grade disease. METHODS: Women aged 30-59 years (n = 1005) were recruited at two well-women clinics in Papua New Guinea. Each woman provided both cervical and vaginal specimens that were tested for high-risk human papillomavirus (hrHPV) DNA using the Xpert HPV Test (Cepheid) at point of care. A subset of paired cervical and vaginal specimens (n = 243) were selected to undergo CINTec® PLUS (Roche) p16/Ki-67 dual-stain cytology and liquid-based cytology (LBC). RESULTS: Fifty-five pairs (22%) were excluded from further analysis because the smears were not assessable. Of the 189 remaining paired specimens, 74 pairs (39.1%) were positive for one or more hrHPV genotypes. When comparing results of the dual stain, the overall percent agreement, positive and negative percent agreements and κ value between the cervical and vaginal specimens were 87.8% (CI 82.3-92.1%), 64.6% (CI 49.5-77.8%), 95.7% (CI 91.0-98.0%) and 0.65 (CI 0.51-0.79%) respectively. The sensitivity of the dual stain performed on the cervical specimen to predict high-grade disease, determined by LBC, was superior to that of the dual stain performed on the vaginal specimen: 100% (CI 84.6-100%) versus 68.2% (CI 45.1-86.1%). CONCLUSION: Although further evaluation may be warranted, these findings indicate that dual-stain testing of vaginal specimens cannot be advocated as part of cervical screening programmes in low- and middle-income countries. However, dual-stain cytology performed on cervical specimens may have a role in quality assurance in such settings.


Asunto(s)
Cuello del Útero/virología , Técnicas Citológicas , Detección Precoz del Cáncer/métodos , Autoevaluación , Manejo de Especímenes/métodos , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Femenino , Humanos , Antígeno Ki-67/análisis , Persona de Mediana Edad , Infecciones por Papillomavirus/diagnóstico , Papúa Nueva Guinea , Sensibilidad y Especificidad , Coloración y Etiquetado/métodos , Neoplasias del Cuello Uterino/genética , Vagina/virología , Displasia del Cuello del Útero/diagnóstico
9.
Mol Psychiatry ; 25(12): 3399-3412, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-30279455

RESUMEN

Next-generation genetic sequencing (NGS) technologies facilitate the screening of multiple genes linked to neurodegenerative dementia, but there are few reports about their use in clinical practice. Which patients would most profit from testing, and information on the likelihood of discovery of a causal variant in a clinical syndrome, are conspicuously absent from the literature, mostly for a lack of large-scale studies. We applied a validated NGS dementia panel to 3241 patients with dementia and healthy aged controls; 13,152 variants were classified by likelihood of pathogenicity. We identified 354 deleterious variants (DV, 12.6% of patients); 39 were novel DVs. Age at clinical onset, clinical syndrome and family history each strongly predict the likelihood of finding a DV, but healthcare setting and gender did not. DVs were frequently found in genes not usually associated with the clinical syndrome. Patients recruited from primary referral centres were compared with those seen at higher-level research centres and a national clinical neurogenetic laboratory; rates of discovery were comparable, making selection bias unlikely and the results generalisable to clinical practice. We estimated penetrance of DVs using large-scale online genomic population databases and found 71 with evidence of reduced penetrance. Two DVs in the same patient were found more frequently than expected. These data should provide a basis for more informed counselling and clinical decision making.


Asunto(s)
Demencia , Secuenciación de Nucleótidos de Alto Rendimiento , Anciano , Demencia/genética , Genómica , Humanos , Mutación/genética , Derivación y Consulta
10.
Mater Sci Eng C Mater Biol Appl ; 99: 83-95, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30889758

RESUMEN

Multifunctional magnetic 3D scaffolds are recently of particular interest because of their applications in hyperthermia-based therapy and localized drug delivery beside of their basic properties to be applied in bone tissue regeneration. In the current study, a magnetic nanocomposite is designed and synthesized through a two-step synthesis strategy in which CoFe2O4 nanoparticles are prepared via sol-gel combustion method and then they are coated through sol-gel method with Mg2SiO4. The characterization relates to the nanocomposite shows that Mg2SiO4-CoFe2O4 is successfully synthesized and it has a core-shell structure. Then, 3D scaffolds are fabricated through polymer sponge technique from the nanocomposite. Physiochemical and biological properties of the scaffolds are assessed in vitro amongst which bioactivity, biodegradability, mechanical properties, hyperthermia capability, controlled release potential, antibacterial activity, cell compatibility and attachment can be mentioned. The results demonstrate that the scaffolds have high porous structure with interconnected porosity and desirable mechanical properties close to cancellous bone. The magnetic scaffold is biodegradable and bioactive and exhibits controlled release of rifampin as an antibiotic drug up to 96 h. Moreover, in the exposure of different magnetic fields it has potential to produce heat for different kinds of hyperthermia-based therapies. The antibacterial activity of drug-loaded scaffold is assessed against S. aureus bacteria. The results suggest that Mg2SiO4-CoFe2O4 nanocomposite scaffold with multiple capabilities has a great potential to be applied in the case of large bone defects which are caused by tumors to not only eradicate remained cancerous tissues, but also prevent infection after surgery and regenerate bone defect.


Asunto(s)
Regeneración Ósea , Huesos/fisiología , Cobalto/química , Compuestos Férricos/química , Silicatos de Magnesio/química , Magnetismo , Nanocompuestos/química , Nanoestructuras/química , Andamios del Tejido/química , Antibacterianos/farmacología , Regeneración Ósea/efectos de los fármacos , Huesos/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Elementos Químicos , Humanos , Concentración de Iones de Hidrógeno , Hipertermia Inducida , Nanocompuestos/ultraestructura , Nanoestructuras/ultraestructura , Porosidad , Espectrometría por Rayos X , Difracción de Rayos X
11.
Mater Sci Eng C Mater Biol Appl ; 96: 765-775, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30606589

RESUMEN

Infection is quite usual for implants after surgery and a systemic administration of antibiotics causes problems before the eradication of bacteria. Localized drug delivery from implants is an effective way by which the mentioned target can be met. In the current work, ordered mesoporous magnesium silicate (OMMS) is coated on plasma electrolytic oxidation (PEO)-modified titanium (Ti) substrate through electrophoretic deposition (EPD) and rifampin as an antibiotic is loaded on OMMS coating to be applied as an antibacterial coating. The immersion test into simulated body fluid and also potentiodynamic polarization assay are adopted to assess the in vitro bioactivity up to 7 days and corrosion resistance of the specimens, respectively. The double surface coatings of PEO and EPD are achieved on Ti substrate and the thickness for each one is found to be 4 and 25 µm, respectively. Regarding to drug delivery capability of OMMS as the EPD coating, the loading capacity is 25% and release trend sustains up to 96 h. The antibacterial activity and also cell viability of OMMS coating are significantly increased with rifampin loading. The results of our study exhibit that OMMS as a multifunctional coating deposited on the PEO-modified Ti substrate improves corrosion resistance, in vitro bioactivity, alkaline phosphatase activity, and mineralization of the substrate. Moreover, rifampin-loaded OMMS coating is not only able to prevent infection, but it also increases the osteogenesis cells viability. Therefore, rifampin-loaded OMMS coating on Ti is potentially regarded appropriate for orthopedic applications.


Asunto(s)
Materiales Biocompatibles Revestidos , Implantes Experimentales , Silicatos de Magnesio , Nanoporos , Titanio , Línea Celular , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacocinética , Materiales Biocompatibles Revestidos/farmacología , Electroforesis , Humanos , Silicatos de Magnesio/química , Silicatos de Magnesio/farmacocinética , Silicatos de Magnesio/farmacología , Titanio/química , Titanio/farmacocinética , Titanio/farmacología
12.
Clin Microbiol Infect ; 25(4): 496-503, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29906593

RESUMEN

OBJECTIVES: To compare the performance of self-collected vaginal (V) specimens with clinician-collected cervical (C) specimens for detection of high-risk human papillomavirus (hrHPV) and cervical disease using the Cepheid Xpert HPV, Roche Cobas 4800 HPV and Hologic Aptima HPV assays. METHODS: Women aged 30-59 years (n = 1005) were recruited at two clinics in Papua New Guinea, and they provided specimens for testing at point-of-care using the Xpert HPV Test, and for subsequent testing using the Cobas HPV (n = 981) and Aptima HPV (n = 983) assays. Liquid-based cytology was performed on C specimens to predict underlying high-grade squamous intraepithelial lesions (HSIL). V specimen results of each assay were evaluated against a constructed reference standard and for detection of HSIL or worse. RESULTS: There was substantial (κ >0.6) agreement in hrHPV detection between V and C specimens across all three assays. The sensitivity, specificity, and positive and negative predictive values of Xpert HPV using self-collected V specimens for the detection of HPV type 16 according to the constructed reference standard were 92.1%, 93.1%, 63.6% and 98.9%, respectively; compared with 90.4%, 94.3%, 67.8% and 98.7% for Cobas 4800 HPV; and 63.2%, 97.2%, 75.0% and 95.3% for Aptima HPV. Similar results were observed for all hrHPV types (combined) and for HPV types 18/45, on all three assays. The detection of any hrHPV using self-collected specimens had high sensitivity (86%-92%), specificity (87%-94%) and negative predictive value (>98%) on all assays for HSIL positivity. CONCLUSIONS: Xpert HPV, using self-collected vaginal specimens, has sufficient accuracy for use in point-of-care 'test-and-treat' cervical screening strategies in high-burden, low-resource settings.


Asunto(s)
Detección Precoz del Cáncer/métodos , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 18/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico , Pruebas en el Punto de Atención/estadística & datos numéricos , Manejo de Especímenes/métodos , Displasia del Cuello del Útero/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Femenino , Humanos , Persona de Mediana Edad , Infecciones por Papillomavirus/virología , Papúa Nueva Guinea , Sensibilidad y Especificidad , Neoplasias del Cuello Uterino/virología , Vagina/virología , Displasia del Cuello del Útero/virología
13.
Climacteric ; 21(3): 235-238, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29488817

RESUMEN

The estimated cervical cancer burden is over ten-fold greater in low- and middle-income countries (LMICs) than in high-income countries. This health gap is thought to be primarily due to limited access to effective screening and treatment programs for cervical pre-cancer and cancer in such settings. The World Health Organization advocates a policy of 'screen and treat' approach to cervical screening in LMICs and subsequently visual inspection of the cervix with acetic acid (VIA) or Lugo's iodine (VILI), followed by ablative cervical cryotherapy if indicated, and this policy has been implemented in many high-burden settings. The performance of VIA/VILI as a primary screening tool for the detection of cervical pre-cancer and cancer has, however, been inconsistent. Recently, many high-income countries have integrated HPV-DNA testing into their cervical cancer screening programs. The comparatively high cost and resource requirements of HPV-based screening have to date prevented many LMICs from doing the same. A significant development has been the entrance of innovative, easy-to-use and highly accurate HPV tests that can be provided at point of care; these could enable LMICs to implement 'test and treat' approaches for cervical cancer screening.


Asunto(s)
Detección Precoz del Cáncer , Infecciones por Papillomavirus/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Biomarcadores de Tumor , Países en Desarrollo , Femenino , Humanos , Tamizaje Masivo/economía , Papillomaviridae , Infecciones por Papillomavirus/complicaciones , Factores Socioeconómicos , Neoplasias del Cuello Uterino/virología
14.
Pathology ; 50(3): 317-321, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29336823

RESUMEN

Quality control (QC) is an essential component of point-of-care testing programs. In the context of a randomised-controlled trial (TTANGO) using GeneXpert (Xpert) Chlamydia trachomatis and Neisseria gonorrhoeae (CT/NG) point-of-care testing in remote areas of Australia, we aimed to develop and utilise a stable positive control material. Bacterial cultures of CT and NG were resuspended together to provide cycle threshold (Ct) values of approximately 25 cycles for both CT and NG when tested on the Xpert CT/NG assay. These positive control suspensions were dried in aliquots, heat inactivated, and then provided to 12 participating health services as research-only QC samples in kit form. At each service, a QC sample was resuspended and tested each month on the Xpert. QC results, including Xpert Ct values, were analysed from each site over 30 months and we calculated costs per QC sample. Overall, at 12 health services there were 89 QC samples tested (average of 8 tests per site per year). Mean Ct values for the 89 controls samples were 25.25 cycles (SD = 1.15) for CT, 24.04 cycles (SD = 1.400) for one NG target and 23.35 cycles (SD = 1.55) for the other NG target. No significant differences in Ct value for CT or NG controls were observed over a trial period of 30 months. Positive QC samples for research use in a trial of a molecular point-of-care assay were inexpensive to produce and stable when stored at 2-8°C. For routine use, additional requirements such as meeting National Association of Testing Authority (NATA) regulations and Therapeutic Goods Administration (TGA) approval will need to be achieved.


Asunto(s)
Infecciones por Chlamydia/diagnóstico , Gonorrea/diagnóstico , Pruebas en el Punto de Atención/normas , Control de Calidad , Manejo de Especímenes/normas , Humanos , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/normas , Técnicas de Amplificación de Ácido Nucleico/métodos , Técnicas de Amplificación de Ácido Nucleico/normas , Manejo de Especímenes/métodos
15.
Eur J Neurol ; 25(1): 24-34, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28817209

RESUMEN

Huntington's disease (HD) is a fully penetrant neurodegenerative disease caused by a dominantly inherited CAG trinucleotide repeat expansion in the huntingtin gene on chromosome 4. In Western populations HD has a prevalence of 10.6-13.7 individuals per 100 000. It is characterized by cognitive, motor and psychiatric disturbance. At the cellular level mutant huntingtin results in neuronal dysfunction and death through a number of mechanisms, including disruption of proteostasis, transcription and mitochondrial function and direct toxicity of the mutant protein. Early macroscopic changes are seen in the striatum with involvement of the cortex as the disease progresses. There are currently no disease modifying treatments; therefore supportive and symptomatic management is the mainstay of treatment. In recent years there have been significant advances in understanding both the cellular pathology and the macroscopic structural brain changes that occur as the disease progresses. In the last decade there has been a large growth in potential therapeutic targets and clinical trials. Perhaps the most promising of these are the emerging therapies aimed at lowering levels of mutant huntingtin. Antisense oligonucleotide therapy is one such approach with clinical trials currently under way. This may bring us one step closer to treating and potentially preventing this devastating condition.


Asunto(s)
Proteína Huntingtina/genética , Enfermedad de Huntington/diagnóstico , Encéfalo/patología , Manejo de la Enfermedad , Pruebas Genéticas , Humanos , Enfermedad de Huntington/genética , Enfermedad de Huntington/patología , Mitocondrias/genética , Neuronas/patología , Expansión de Repetición de Trinucleótido
16.
Brain Stimul ; 10(6): 1102-1111, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28807846

RESUMEN

BACKGROUND: Electrophysiological measures can help understand brain function both in healthy individuals and in the context of a disease. Given the amount of information that can be extracted from these measures and their frequent use, it is essential to know more about their inherent reliability. OBJECTIVE/HYPOTHESIS: To understand the reliability of electrophysiology measures in healthy individuals. We hypothesized that measures of threshold and latency would be the most reliable and least susceptible to methodological differences between study sites. METHODS: Somatosensory evoked potentials from 112 control participants; long-latency reflexes, transcranial magnetic stimulation with resting and active motor thresholds, motor evoked potential latencies, input/output curves, and short-latency sensory afferent inhibition and facilitation from 84 controls were collected at 3 visits over 24 months at 4 Track-On HD study sites. Reliability was assessed using intra-class correlation coefficients for absolute agreement, and the effects of reliability on statistical power are demonstrated for different sample sizes and study designs. RESULTS: Measures quantifying latencies, thresholds, and evoked responses at high stimulator intensities had the highest reliability, and required the smallest sample sizes to adequately power a study. Very few between-site differences were detected. CONCLUSIONS: Reliability and susceptibility to between-site differences should be evaluated for electrophysiological measures before including them in study designs. Levels of reliability vary substantially across electrophysiological measures, though there are few between-site differences. To address this, reliability should be used in conjunction with theoretical calculations to inform sample size and ensure studies are adequately powered to detect true change in measures of interest.


Asunto(s)
Potenciales Evocados Motores/fisiología , Potenciales Evocados Somatosensoriales/fisiología , Estimulación Magnética Transcraneal/métodos , Estimulación Magnética Transcraneal/normas , Adulto , Estudios de Cohortes , Fenómenos Electrofisiológicos/fisiología , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Descanso/fisiología
17.
Chem Commun (Camb) ; 53(57): 8081-8084, 2017 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-28677694

RESUMEN

The famous α-Fe active sites in Fe-zeolites have recently been revealed to correspond to mononuclear high-spin iron(ii) centres in square planar coordination environments. Here we report a first iron siloxide complex which represents a faithful structural and spectroscopic model of such sites. Notably, also an allogon with a distorted structure exists and could be crystallised.

18.
J Clin Microbiol ; 55(6): 1915-1919, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28381611

RESUMEN

Mycoplasma genitalium is a significant pathogen for which first-line treatment is becoming less effective due to increased resistance to macrolides. As conventional culture and antimicrobial susceptibility testing is not feasible for routine detection of this pathogen, molecular markers such as detection of mutations in the 23S rRNA gene have been described to predict resistance. Recently, a novel multiplex quantitative PCR (qPCR) assay, ResistancePlus MG, has been described for the simultaneous detection of Mycoplasma genitalium and macrolide resistance. In the current study, the clinical performance of the assay was evaluated on 1,089 consecutive urine and anogenital swab samples in symptomatic and asymptomatic male and female patients. Overall, 6.0% were positive for M. genitalium, with 63.1% having macrolide resistance-associated mutations. Compared to the laboratory-validated qPCR method targeting the 16S rRNA gene and Sanger sequencing to determine 23S rRNA mutations, the sensitivity and specificity of M. genitalium detection were 98.5% and 100% and for detection of macrolide resistance mutations were 100.0% and 96.2%, respectively. This assay offers a considerable advantage in clinical settings for M. genitalium testing by making the results of macrolide resistance and mutation analyses simultaneously available, which is increasingly important with escalating macrolide resistance.


Asunto(s)
Farmacorresistencia Bacteriana , Pruebas de Sensibilidad Microbiana/métodos , Técnicas de Diagnóstico Molecular/métodos , Reacción en Cadena de la Polimerasa Multiplex/métodos , Infecciones por Mycoplasma/diagnóstico , Mycoplasma genitalium/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Canal Anal/microbiología , Antibacterianos/farmacología , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Femenino , Genitales/microbiología , Humanos , Macrólidos/farmacología , Masculino , Infecciones por Mycoplasma/microbiología , Mycoplasma genitalium/efectos de los fármacos , Mycoplasma genitalium/aislamiento & purificación , Estudios Prospectivos , ARN Ribosómico 16S/genética , ARN Ribosómico 23S/genética , Sensibilidad y Especificidad , Orina/microbiología
19.
Eur J Clin Microbiol Infect Dis ; 36(7): 1297-1303, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28220321

RESUMEN

High-resolution screening methodologies which enable the differentiation of Chlamydia trachomatis at the strain level, directly from clinical samples, can provide the detailed information required for epidemiological questions such as the dynamics of treatment failure. In addition, they give a detailed snapshot of circulating C. trachomatis genetic variation, data which are currently lacking for the Australian population. In the context of two Australian clinical trials, we assessed the genetic diversity of C. trachomatis and compared these to strains circulating globally. We used high-resolution multilocus sequence typing (MLST) of five highly variable genetic regions of C. trachomatis to examine variation in Australia. Samples with established genovars were drawn from a pool of 880 C. trachomatis-positive samples from two clinical studies, whereby 76 sample pairs which remained C. trachomatis-positive for the same genovar after treatment underwent MLST analysis to distinguish between treatment failure and reinfection. MLST analysis revealed a total of 25 sequence types (STs), six new allele variants and seven new STs not described anywhere else in the world, when compared to those in the international C. trachomatis MLST database. Of the eight most common global STs, seven were found in Australia (four derived from men who have sex with men (MSM) and three from heterosexuals). Newly identified STs were predominantly found in samples from the MSM population. In conclusion, MLST provided a diverse C. trachomatis strain profile, with novel circulating STs, and could be used to identify local sexual networks to focus on interventions such as testing and partner notification to prevent reinfection.


Asunto(s)
Infecciones por Chlamydia/microbiología , Chlamydia trachomatis/clasificación , Chlamydia trachomatis/genética , Variación Genética , Tipificación de Secuencias Multilocus , Australia/epidemiología , Infecciones por Chlamydia/epidemiología , Chlamydia trachomatis/aislamiento & purificación , Ensayos Clínicos como Asunto , Femenino , Humanos , Masculino , Epidemiología Molecular , Población Urbana
20.
J Microbiol Methods ; 133: 66-68, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-28042056

RESUMEN

We investigated the utility of quantitative PCR assays for diagnosis of bacterial vaginosis and found that while the best model utilized bacterial copy number adjusted for total bacterial load (sensitivity=98%, specificity=93%, AUC=0.95[95%CI=0.93,0.97]), adjusting for total bacterial or human cell load did not consistently increase the diagnostic performance of the assays.


Asunto(s)
Carga Bacteriana , Técnicas de Diagnóstico Molecular , Reacción en Cadena en Tiempo Real de la Polimerasa , Vaginosis Bacteriana/diagnóstico , Actinobacteria/aislamiento & purificación , Femenino , Gardnerella vaginalis/aislamiento & purificación , Humanos , Sensibilidad y Especificidad , Vagina/microbiología , Vaginosis Bacteriana/microbiología
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