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1.
Clin Infect Dis ; 76(3): e1328-e1334, 2023 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-35959938

RESUMEN

BACKGROUND: Influenza circulated at historically low levels during 2020/2021 due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic travel restrictions. In Australia, international arrivals were required to undergo a 14-day hotel quarantine to limit new introduction of SARS-CoV-2. METHODS: We usedtesting data for travelers arriving on repatriation flights to Darwin, Australia, from 3 January 2021 to 11 October 2021 to identify importations of influenza virus into Australia. We used this information to estimate the risk of a case exiting quarantine while still infectious. Influenza-positive samples were sequenced, and cases were followed up to identify transmission clusters. Data on the number of cases and total passengers were used to infer the risk of influenza cases exiting quarantine while infectious. RESULTS: Despite very low circulation of influenza globally, 42 cases were identified among 15 026 returned travelers, of which 30 were A(H3N2), 2 were A(H1N1)pdm09, and 10 were B/Victoria. Virus sequencing data identified potential in-flight transmission, as well as independent infections prior to travel. Under the quarantine strategy in place at the time, the probability that these cases could initiate influenza outbreaks in Australia neared 0. However, this probability rose as quarantine requirements relaxed. CONCLUSIONS: Detection of influenza virus infections in repatriated travelers provided a source of influenza viruses otherwise unavailable and enabled development of the A(H3N2) vaccine seed viruses included in the 2022 Southern Hemisphere influenza vaccine. Failure to test quarantined returned travelers for influenza represents a missed opportunity for enhanced surveillance to better inform public health preparedness.


Asunto(s)
COVID-19 , Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Humanos , Gripe Humana/epidemiología , Gripe Humana/prevención & control , Cuarentena , Subtipo H3N2 del Virus de la Influenza A , SARS-CoV-2/genética , COVID-19/epidemiología , COVID-19/prevención & control , Victoria
2.
J Neurosci Res ; 101(12): 1884-1899, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37772463

RESUMEN

Eclampsia, new-onset seizures in pregnancy, can complicate preeclampsia, a hypertensive pregnancy disorder. The mechanisms contributing to increased risk of seizures in preeclampsia are not fully known. One mechanism could be abnormal endocannabinoid system (ECS) activity and impaired neuromodulation. Indeed, increased placental cannabinoid receptor 1 (CB1R) expression and reduced serum anandamide, a CB1R ligand, have been reported in preeclampsia patients. We hypothesized that reduced uterine perfusion pressure (RUPP), used to mimic preeclampsia, leads to changes in hippocampal CB1R expression, and that manipulating CB1R activity will change seizure severity in RUPP mice. Pregnant mice underwent sham or RUPP surgery on gestational day (GD)13.5. On GD18.5, mice received: no drug treatment, pentylenetetrazol (PTZ, 40 mg/kg), Rimonabant (10 mg/kg) + PTZ, or 2-AG (1 mg/kg) + PTZ. Behaviors were video recorded (15 min for Rimonabant and 2-AG, followed by 30 min for PTZ), and the hippocampus was harvested. The expression of CB1R and ECS proteins was measured in hippocampal homogenates, synaptosomes, and cytosol. Hippocampal CB1R increased in homogenates and cytosolic fraction, and was unchanged in synaptosomes of RUPP mice. Increased CB1R colocalization on glutamate-releasing neurons within hippocampal CA1 was observed in RUPP mice. Rimonabant modestly increased seizure scores over time in RUPP mice. PTZ after rimonabant pretreatment increased seizure scores and duration, while reducing latency in sham mice, with little to no change in RUPP mice. Furthermore, RUPP mice had lower seizure scores over time than sham following CB1R blockade and activation. These data suggest that RUPP modifies CB1R activity prior to seizure induction, which protects mice from worse seizure outcomes.


Asunto(s)
Cannabinoides , Hipertensión , Preeclampsia , Humanos , Ratas , Ratones , Embarazo , Animales , Femenino , Placenta , Ratas Sprague-Dawley , Rimonabant/farmacología , Receptores de Cannabinoides , Modelos Animales de Enfermedad , Convulsiones/inducido químicamente , Presión Sanguínea/fisiología , Perfusión , Isquemia
3.
BMC Psychiatry ; 23(1): 750, 2023 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-37833705

RESUMEN

BACKGROUND: This case report is of a patient with psychosis secondary to thyrotoxicosis that persisted and reemerged after definitive treatment of thyroidectomy, which is a unique occurrence in the literature. CASE PRESENTATION: This patient is a male between 30 and 35 years of age with a history of Graves Disease and no past psychiatric history who was admitted to the hospital due to psychosis secondary to thyrotoxicosis. The thyrotoxicosis was treated with surgical removal, but the psychotic symptoms persisted after surgery and normalization of standard thyroid functional measures. The symptoms were of sufficient significance for inpatient psychiatric hospitalization, a rare occurrence. Ultimately after an extended stay in the psychiatric unit, the patient's symptoms stabilized with a second-generation antipsychotic, and the patient was discharged from the psychiatric unit. CONCLUSION: This case is evidence that the link between psychosis and hyperthyroidism is still poorly understood due to the patient's psychotic symptoms persisting after the definitive treatment of thyroidectomy and the fact that it required anti-psychotic medications for normalization.


Asunto(s)
Enfermedad de Graves , Trastornos Psicóticos , Tirotoxicosis , Masculino , Humanos , Tiroidectomía/efectos adversos , Tirotoxicosis/complicaciones , Tirotoxicosis/cirugía , Enfermedad de Graves/complicaciones , Enfermedad de Graves/cirugía , Enfermedad de Graves/tratamiento farmacológico , Trastornos Psicóticos/complicaciones
4.
Emerg Infect Dis ; 28(7): 1527-1530, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35483111

RESUMEN

Epidemiologic and genomic investigation of SARS-CoV-2 infections associated with 2 repatriation flights from India to Australia in April 2021 indicated that 4 passengers transmitted SARS-CoV-2 to >11 other passengers. Results suggest transmission despite mandatory mask use and predeparture testing. For subsequent flights, predeparture quarantine and expanded predeparture testing were implemented.


Asunto(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiología , Genoma Viral , Genómica , Humanos , Cuarentena , SARS-CoV-2/genética
5.
Handb Exp Pharmacol ; 271: 137-162, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-33834276

RESUMEN

Nalfurafine has been used clinically in Japan for treatment of itch in kidney dialysis patients and in patients with chronic liver diseases. A one-year post-marketing study showed nalfurafine to be safe and efficacious without producing side effects of typical KOR agonists such as anhedonia and psychotomimesis. In this chapter, we summarize in vitro characterization and in vivo preclinical studies on nalfurafine. In vitro, nalfurafine is a highly potent and moderately selective KOR full agonist; however, whether it is a biased KOR agonist is a matter of debate. In animals, nalfurafine produced anti-pruritic effects in a dose range lower than that caused side effects, including conditioned place aversion (CPA), hypolocomotion, motor incoordination, consistent with the human data. In addition, nalfurafine showed antinociceptive effects in several pain models at doses that did not cause the side effects mentioned above. It appears to be effective against inflammatory pain and mechanical pain, but less so against thermal pain, particularly high-intensity thermal pain. U50,488H and nalfurafine differentially modulated several signaling pathways in a brain region-specific manners. Notably, U50,488H, but not nalfurafine, activated the mTOR pathway, which contributed to U50,488H-induced CPA. Because of its lack of side effects associated with typical KOR agonists, nalfurafine has been investigated as a combination therapy with an MOR ligand for pain treatment and for its effects on opioid use disorder and alcohol use disorder, and results indicate potential usefulness for these indications. Thus, although in vitro data regarding uniqueness of nalfurafine in terms of signaling at the KOR are somewhat equivocal, in vivo results support the assertion that nalfurafine is an atypical KOR agonist with a significantly improved side-effect profile relative to typical KOR agonists.


Asunto(s)
Morfinanos , Compuestos de Espiro , Animales , Humanos , Morfinanos/farmacología , Morfinanos/uso terapéutico , Dolor , Receptores Opioides kappa , Compuestos de Espiro/farmacología
6.
BMC Infect Dis ; 21(1): 584, 2021 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-34134657

RESUMEN

BACKGROUND: The demographic of Northern Territory prison population differs than elsewhere in Australia and the prevalence of hepatitis B and hepatitis C may therefore be somewhat different from other jurisdictions. There has been no study which has specifically described the serological results of a large proportion of prisoners in Northern Territory correctional facilities over an extended period of time. METHODS: This retrospective longitudinal study reviewed serological results and testing rates for hepatitis B, and hepatitis C performed in correctional facilities in the Northern Territory of Australia between July 1st, 2003 and June 30th, 2017. RESULTS: The proportion of positive records over 14 years for hepatitis B surface antigen (HBsAg) was 641/12,066 (5.3, 95% CI 4.9-5.7), for hepatitis B core antibody (anti-HBc) 4937/12,138 (40.1, 95%CI 39.8-41.6), for hepatitis B surface antibody (anti-HBs) 6966/13,303 (52.4, 95% CI 51.5-53.2), and for hepatitis C antibody 569/12,153 (4.7, 95% CI 4.3-5.1). The proportion of prisoners tested for hepatitis B and hepatitis C has decreased since 2015, while a high proportion of prisoners remain non-immune to hepatitis B. CONCLUSION: There is a relatively high proportion of positive serological markers of hepatitis B, and a lower proportion of positive hepatitis C serology in the Northern Territory's correctional facilities compared to overall Australian rates. As the proportion of prisoners tested for hepatitis B and C has decreased recently, and a high proportion of prisoners remain non-immune to hepatitis B, there are opportunities to increase testing and vaccination rates in this population.


Asunto(s)
Hepatitis B/diagnóstico , Hepatitis C/diagnóstico , Adulto , Biomarcadores/sangre , Instalaciones Correccionales/estadística & datos numéricos , Bases de Datos Factuales , Femenino , Hepatitis B/epidemiología , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis C/epidemiología , Anticuerpos contra la Hepatitis C/sangre , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Northern Territory/epidemiología , Prevalencia , Estudios Retrospectivos , Adulto Joven
7.
Behav Pharmacol ; 31(8): 792-797, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32804774

RESUMEN

Mu-opioid receptor (MOR) agonists are highly efficacious for the treatment of pain but have significant abuse liability. Recently, we reported that nalfurafine, when combined with oxycodone at a certain ratio, reduced the reinforcing effects of oxycodone in rats while producing additive antinociceptive effects. Questions remain, however, including if the combination will function as a reinforcer in drug-naïve rats, and if the combination produces aversive effects that could explain nalfurafine's ability to reduce oxycodone self-administration? In the present study, we investigated nalfurafine's ability to reduce acquisition of oxycodone self-administration when the two were self-administered as a mixture in drug-naïve rats and nalfurafine's ability to attenuate a conditioned place preference (CPP) induced by oxycodone. In the self-administration study, male Sprague-Dawley rats self-administered intravenous injections of oxycodone (0.056 mg/kg/injection), an oxycodone/nalfurafine combination (0.056/0.0032 mg/kg/injection), or saline under fixed-ratio schedules of reinforcement for 20 days to compare rates of acquisition of drug taking. In the CPP assay, male Sprague-Dawley rats received subcutaneous injections of either saline, oxycodone (3.2 mg/kg), nalfurafine (0.18 mg/kg), or an oxycodone/nalfurafine combination at the same ratio used in the self-administration study (3.2 mg/kg/0.18 mg/kg). All subjects self-administering oxycodone alone met acquisition criteria. However, only 13% of subjects self-administering oxycodone/nalfurafine met criteria, and no subjects acquired self-administration of saline. Oxycodone, but not nalfurafine alone or the oxycodone/nalfurafine combination, produced rewarding effects in rats in the CPP test. These findings suggest that the combination of oxycodone and nalfurafine will be less habit forming in opioid-naïve patients than oxycodone alone.


Asunto(s)
Morfinanos/farmacología , Trastornos Relacionados con Opioides/tratamiento farmacológico , Receptores Opioides kappa/agonistas , Compuestos de Espiro/farmacología , Analgésicos Opioides/farmacología , Animales , Condicionamiento Clásico/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Masculino , Morfinanos/metabolismo , Trastornos Relacionados con Opioides/prevención & control , Oxicodona/efectos adversos , Oxicodona/farmacología , Ratas , Ratas Sprague-Dawley , Receptores Opioides/agonistas , Receptores Opioides/metabolismo , Receptores Opioides kappa/metabolismo , Refuerzo en Psicología , Recompensa , Autoadministración , Compuestos de Espiro/metabolismo , Trastornos Relacionados con Sustancias/tratamiento farmacológico , Trastornos Relacionados con Sustancias/prevención & control
8.
Euro Surveill ; 24(33)2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31431210

RESUMEN

BackgroundInterseasonal influenza outbreaks are not unusual in countries with temperate climates and well-defined influenza seasons. Usually, these are small and diminish before the main influenza season begins. However, the 2018/19 summer-autumn interseasonal influenza period in Australia saw unprecedented large and widespread influenza outbreaks.AimOur objective was to determine the extent of the intense 2018/19 interseasonal influenza outbreaks in Australia epidemiologically and examine the genetic, antigenic and structural properties of the viruses responsible for these outbreaks.MethodsThis observational study combined the epidemiological and virological surveillance data obtained from the Australian Government Department of Health, the New South Wales Ministry of Health, sentinel outpatient surveillance, public health laboratories and data generated by the World Health Organization Collaborating Centre for Reference and Research on Influenza in Melbourne and the Singapore Agency for Science, Technology and Research.ResultsThere was a record number of laboratory-confirmed influenza cases during the interseasonal period November 2018 to May 2019 (n= 85,286; 5 times the previous 3-year average) and also more institutional outbreaks, hospitalisations and deaths, than what is normally seen.ConclusionsThe unusually large interseasonal influenza outbreaks in 2018/19 followed a mild 2018 influenza season and resulted in a very early start to the 2019 influenza season across Australia. The reasons for this unusual event have yet to be fully elucidated but are likely to be a complex mix of climatic, virological and host immunity-related factors. These outbreaks reinforce the need for year-round surveillance of influenza, even in temperate climates with strong seasonality patterns.


Asunto(s)
Notificación de Enfermedades/estadística & datos numéricos , Brotes de Enfermedades , Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza B/aislamiento & purificación , Gripe Humana/epidemiología , Vigilancia de la Población/métodos , Adolescente , Adulto , Anciano , Australia/epidemiología , Niño , Preescolar , Femenino , Hemaglutininas Virales , Humanos , Lactante , Virus de la Influenza A/clasificación , Virus de la Influenza A/genética , Virus de la Influenza B/genética , Gripe Humana/diagnóstico , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Nueva Gales del Sur , Filogenia , Estaciones del Año , Vigilancia de Guardia
9.
Hum Brain Mapp ; 39(6): 2500-2513, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29468773

RESUMEN

MRI has become an indispensable tool for brain volumetric studies, with the hippocampus an important region of interest. Automation of the MRI segmentation process has helped advance the field by facilitating the volumetric analysis of larger cohorts and more studies. FreeSurfer has emerged as the de facto standard tool for these analyses, but studies validating its output are all based on older versions. To characterize FreeSurfer's validity, we compare several versions of FreeSurfer software with traditional hand-tracing. Using MRI images of 262 males and 402 females aged 38 to 84, we directly compare estimates of hippocampal volume from multiple versions of FreeSurfer, its hippocampal subfield routines, and our manual tracing protocol. We then use those estimates to assess asymmetry and atrophy, comparing performance of different estimators with each other and with brain atrophy measures. FreeSurfer consistently reports larger volumes than manual tracing. This difference is smaller in larger hippocampi or older people, with these biases weaker in version 6.0.0 than prior versions. All methods tested agree qualitatively on rightward asymmetry and increasing atrophy in older people. FreeSurfer saves time and money, and approximates the same atrophy measures as manual tracing, but it introduces biases that could require statistical adjustments in some studies.


Asunto(s)
Hipocampo/diagnóstico por imagen , Longevidad/fisiología , Imagen por Resonancia Magnética , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Lateralidad Funcional , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad
10.
Emerg Infect Dis ; 23(9): 1478-1485, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28820128

RESUMEN

Neisseria gonorrhoeae antimicrobial resistance (AMR) is a globally recognized health threat; new strategies are needed to enhance AMR surveillance. The Northern Territory of Australia is unique in that 2 different first-line therapies, based primarily on geographic location, are used for gonorrhea treatment. We tested 1,629 N. gonorrhoeae nucleic acid amplification test-positive clinical samples, collected from regions where ceftriaxone plus azithromycin or amoxicillin plus azithromycin are recommended first-line treatments, by using 8 N. gonorrhoeae AMR PCR assays. We compared results with those from routine culture-based surveillance data. PCR data confirmed an absence of ceftriaxone resistance and a low level of azithromycin resistance (0.2%), and that penicillin resistance was <5% in amoxicillin plus azithromycin regions. Rates of ciprofloxacin resistance and penicillinase-producing N. gonorrhoeae were lower when molecular methods were used. Molecular methods to detect N. gonorrhoeae AMR can increase the evidence base for treatment guidelines, particularly in settings where culture-based surveillance is limited.


Asunto(s)
Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana/genética , Gonorrea/epidemiología , Neisseria gonorrhoeae/genética , Vigilancia en Salud Pública , Adulto , Amoxicilina/uso terapéutico , Azitromicina/uso terapéutico , Ceftriaxona/uso terapéutico , Ciprofloxacina/uso terapéutico , Femenino , Gonorrea/tratamiento farmacológico , Gonorrea/microbiología , Gonorrea/transmisión , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Epidemiología Molecular , Tipificación de Secuencias Multilocus , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/aislamiento & purificación , Northern Territory/epidemiología , Penicilinas/uso terapéutico
11.
Behav Pharmacol ; 28(5): 386-393, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-28537943

RESUMEN

Benzodiazepines (BZs) are relatively safe when administered alone. However, these drugs can produce severe side effects when coadministered with ethanol. Despite these adverse consequences, rates of concurrent BZ and ethanol misuse are increasing, and it is unclear whether this behavior is maintained by an enhanced reinforcing effect of the mixture. To address this issue, the current study compared the reinforcing effectiveness of sucrose solutions mixed with midazolam, ethanol, or both. Eight male rats were trained to orally self-administer solutions of either sucrose (S), sucrose+midazolam (SM), sucrose+ethanol (SE), or sucrose+midazolam+ethanol (SME). The response requirement was increased between sessions until the number of reinforcers earned was zero and the relationship between response requirement and reinforcers earned was analyzed using the exponential model of demand. Although baseline intake was similar across drug conditions, consumption of SM was least affected by increases in cost, indicating that it possessed the highest reinforcing effectiveness (i.e. least elastic). The reinforcing effectiveness of S, SE, and SME did not differ significantly. The finding that the reinforcing effectiveness of the SME was less than that of SM does not support the supposition that BZ and ethanol coadministration is maintained by a higher reinforcing effectiveness of the mixture.


Asunto(s)
Midazolam/farmacología , Consumo de Bebidas Alcohólicas/metabolismo , Animales , Benzodiazepinas , Etanol/administración & dosificación , Etanol/metabolismo , Etanol/farmacología , Masculino , Midazolam/administración & dosificación , Midazolam/metabolismo , Ratas , Esquema de Refuerzo , Refuerzo en Psicología , Autoadministración , Sacarosa/administración & dosificación , Sacarosa/metabolismo
12.
Clin Infect Dis ; 63(12): 1591-1598, 2016 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-27682063

RESUMEN

BACKGROUND: Antimicrobial resistance (AMR) by Neisseria gonorrhoeae is considered a serious global threat. METHODS: In this nationwide study, we used MassARRAY iPLEX genotyping technology to examine the epidemiology of N. gonorrhoeae and associated AMR in the Australian population. All available N. gonorrhoeae isolates (n = 2452) received from Australian reference laboratories from January to June 2012 were included in the study. Genotypic data were combined with phenotypic AMR information to define strain types. RESULTS: A total of 270 distinct strain types were observed. The 40 most common strain types accounted for over 80% of isolates, and the 10 most common strain types accounted for almost half of all isolates. The high male to female ratios (>94% male) suggested that at least 22 of the top 40 strain types were primarily circulating within networks of men who have sex with men (MSM). Particular strain types were also concentrated among females: two strain types accounted for 37.5% of all isolates from females. Isolates harbouring the mosaic penicillin binding protein 2 (PBP2)-considered a key mechanism for cephalosporin resistance-comprised 8.9% of all N. gonorrhoeae isolates and were primarily observed in males (95%). CONCLUSIONS: This large scale epidemiological investigation demonstrated that N. gonorrhoeae infections are dominated by relatively few strain types. The commonest strain types were concentrated in MSM in urban areas and Indigenous heterosexuals in remote areas, and we were able to confirm a resurgent epidemic in heterosexual networks in urban areas. The prevalence of mosaic PBP2 harboring N. gonorrhoeae strains highlight the ability for new N. gonorrhoeae strains to spread and become established across populations.


Asunto(s)
Antibacterianos/uso terapéutico , Gonorrea/epidemiología , Neisseria gonorrhoeae/efectos de los fármacos , Estudios Transversales , Femenino , Técnicas de Genotipaje , Gonorrea/tratamiento farmacológico , Gonorrea/microbiología , Homosexualidad Masculina , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Epidemiología Molecular , Neisseria gonorrhoeae/genética , Polimorfismo de Nucleótido Simple , Especificidad de la Especie
13.
J Antimicrob Chemother ; 71(11): 3090-3095, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27494921

RESUMEN

OBJECTIVES: The objective of this study was to develop a real-time PCR assay targeting the gonococcal porB gene (PorB-PCR) for predicting susceptibility of Neisseria gonorrhoeae to penicillin. This complements a previously described PCR assay for detecting penicillinase-producing N. gonorrhoeae (PPNG) developed by our laboratory (PPNG-PCR). METHODS: The PorB-PCR assay was designed using six probes to characterize various combinations of amino acids at positions 101 and 102 of the PorB1b class protein, including the WT G101/A102 and mutant G101K/A102D, G101K/A102N and G101K/A102G sequences, as well as the PorB1a sequence. The ability of these sequences to predict penicillin susceptibility was initially assessed using 2307 N. gonorrhoeae isolates from throughout Australia for which phenotypic susceptibility data were available. The assay was then applied to N. gonorrhoeae-positive clinical specimens (n = 70). Specificity was assessed by testing commensal Neisseria strains (n = 75) and N. gonorrhoeae-negative clinical specimens (n = 171). RESULTS: Testing of the 2307 N. gonorrhoeae isolates using PorB-PCR to detect G101/A102 and PorB1a sequences identified a total of 78.4% (61.2% and 17.2%, respectively) of penicillin-susceptible isolates with specificities of 97.4% and 99.3% and positive predictive values of 98.8% and 98.9%, where PPNG strains were simultaneously identified and excluded. Similar performance data were obtained when the PorB-PCR assay was applied to the N. gonorrhoeae-positive clinical specimens. No false-positive results were observed for the N. gonorrhoeae-negative samples and no cross-reactions were observed with the non-gonococcal species. CONCLUSIONS: When used in parallel with the previously described PPNG-PCR, the PorB-PCR approach has the potential to facilitate individualized treatment of gonorrhoea using penicillin.


Asunto(s)
Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana/métodos , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/genética , Penicilinas/farmacología , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Australia , Técnicas de Genotipaje/métodos , Humanos , Sondas de Oligonucleótidos/genética , Porinas/genética , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad
14.
J Antimicrob Chemother ; 71(2): 353-6, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26538505

RESUMEN

OBJECTIVES: The objective of this study was to develop a real-time PCR method for specific detection of the gonococcal GyrA amino acid 91 locus directly in clinical samples so as to predict Neisseria gonorrhoeae ciprofloxacin susceptibility. METHODS: The real-time PCR assay, GyrA91-PCR, was designed using two probes, one for detection of the WT S91 sequence and the other for detection of the S91F alteration. The performance of the assay was initially assessed using characterized N. gonorrhoeae isolates (n = 70), a panel of commensal Neisseria and Moraxella species (n = 55 isolates) and clinical samples providing negative results by a commercial N. gonorrhoeae nucleic acid amplification test (NAAT) method (n = 171). The GyrA91-PCR was then applied directly to N. gonorrhoeae NAAT-positive clinical samples (n = 210) from the year 2014 for which corresponding N. gonorrhoeae isolates with susceptibility results were also available. RESULTS: The GyrA91-PCR accurately characterized the GyrA 91 locus of all 70 N. gonorrhoeae isolates (sensitivity = 100%, 95% CI = 94.9%-100%), whereas all non-gonococcal isolates and N. gonorrhoeae NAAT-negative clinical samples gave negative results by the GyrA91-PCR (specificity = 100%, 95% CI = 98.4%-100%). When applied to the 210 N. gonorrhoeae NAAT-positive clinical samples, the GyrA91-PCR successfully characterized 195 samples (92.9%, 95% CI = 88.5%-95.9%). When compared with the corresponding bacterial culture results, positivity by the GyrA91-PCR WT probe correctly predicted N. gonorrhoeae susceptibility to ciprofloxacin in 161 of 162 (99.4%, 95% CI = 96.6%-99.9%) samples. CONCLUSIONS: The use of a PCR assay for detection of mutation in gyrA applied directly to clinical samples can predict ciprofloxacin susceptibility in N. gonorrhoeae.


Asunto(s)
Antibacterianos/farmacología , Ciprofloxacina/farmacología , Girasa de ADN/genética , Farmacorresistencia Bacteriana , Genotipo , Neisseria gonorrhoeae/efectos de los fármacos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Humanos , Moraxella/efectos de los fármacos , Moraxella/genética , Neisseria gonorrhoeae/genética
16.
J Clin Microbiol ; 53(8): 2706-8, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25994166

RESUMEN

A multitarget PCR was developed for the direct detection of penicillinase-producing Neisseria gonorrhoeae (PPNG). The assay was validated by testing 342 PPNG isolates and 415 clinical samples. The method is suitable for routine detection of PPNG strains. Its multitarget approach reduces the potential for false-negative results caused by sequence variations.


Asunto(s)
Farmacorresistencia Bacteriana , Gonorrea/microbiología , Neisseria gonorrhoeae/enzimología , Penicilinasa/genética , Reacción en Cadena de la Polimerasa/métodos , Monitoreo Epidemiológico , Gonorrea/epidemiología , Humanos , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/genética
17.
Cancer Cell ; 12(6): 559-71, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18068632

RESUMEN

Fibroblast Growth Factor Receptor-1 (FGFR1) is commonly overexpressed in advanced prostate cancer (PCa). To investigate causality, we utilized an inducible FGFR1 (iFGFR1) prostate mouse model. Activation of iFGFR1 with chemical inducers of dimerization (CID) led to highly synchronous, step-wise progression to adenocarcinoma that is linked to an epithelial-to-mesenchymal transition (EMT). iFGFR1 inactivation by CID withdrawal led to full reversion of prostatic intraepithelial neoplasia, whereas PCa lesions became iFGFR1-independent. Gene expression profiling at distinct stages of tumor progression revealed an increase in EMT-associated Sox9 and changes in the Wnt signaling pathway, including Fzd4, which was validated in human PCa. The iFGFR1 model clearly implicates FGFR1 in PCa progression and demonstrates how CID-inducible models can help evaluate candidate molecules in tumor progression and maintenance.


Asunto(s)
Células Epiteliales/enzimología , Células Epiteliales/patología , Mesodermo/enzimología , Mesodermo/patología , Neoplasias de la Próstata/enzimología , Neoplasias de la Próstata/patología , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/biosíntesis , Animales , Dimerización , Progresión de la Enfermedad , Activación Enzimática , Inducción Enzimática , Regulación Neoplásica de la Expresión Génica , Proteínas del Grupo de Alta Movilidad/metabolismo , Humanos , Inmunohistoquímica , Masculino , Ratones , Metástasis de la Neoplasia , Neoplasia Intraepitelial Prostática/genética , Neoplasias de la Próstata/genética , Inducción de Remisión , Factor de Transcripción SOX9 , Transducción de Señal , Factores de Transcripción/metabolismo
18.
Antimicrob Agents Chemother ; 58(12): 7576-8, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25267684

RESUMEN

Penicillinase-producing Neisseria gonorrhoeae (PPNG) carrying the blaTEM-135 gene is of particular concern, as it is considered a stepping stone toward resistance to extended-spectrum cephalosporins. Here, we sought to characterize plasmid types and the occurrence of the blaTEM-135 gene for N. gonorrhoeae clinical isolates from Australia. We found that blaTEM-135 was prevalent in Australian PPNG and was detected on all three major plasmid types.


Asunto(s)
Resistencia a las Cefalosporinas/genética , Neisseria gonorrhoeae/genética , Resistencia a las Penicilinas/genética , Penicilinasa/genética , Plásmidos/química , Antibacterianos/farmacología , Australia , Técnicas de Tipificación Bacteriana , Cefalosporinas/farmacología , Gonorrea/microbiología , Gonorrea/transmisión , Humanos , Pruebas de Sensibilidad Microbiana , Neisseria gonorrhoeae/clasificación , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/aislamiento & purificación , Penicilinas/farmacología , Plásmidos/clasificación
19.
Aust N Z J Public Health ; 48(4): 100172, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39059095

RESUMEN

BACKGROUND: We describe the recent temporal patterns of respiratory syncytial virus (RSV) and influenza virus detections in the Northern Territory (NT) of Australia, between 2020 and 2023. METHODS: This retrospective analysis of patients presenting with respiratory diseases utilised a multiplex viral nucleic acid detection assay for RSV, influenza and SARS Cov2 (COVID-19) to determine the relative frequency of non-COVID-19 respiratory viral detections by age and month during the study period. RESULTS: During this period of the NT COVID-19 epidemic, disruption of the usual annual wet season RSV outbreak patterns occurred, and the yearly influenza peak was absent for two annual cycles. Our data also reveals that 25% of RSV infections were occurring in patients greater than 40 years of age, compared to 32% of influenza infections presenting in the same period, documenting a greater burden of adult disease than previously documented in the NT. CONCLUSIONS: Loss of non-COVID-19 viral seasonality and a substantial unrecognised RSV adult burden were noted. We will continue to monitor seasonality, and the RSV burden and this will help to target the populations benefiting from recently released RSV vaccine.


Asunto(s)
COVID-19 , Gripe Humana , Infecciones por Virus Sincitial Respiratorio , Estaciones del Año , Humanos , Infecciones por Virus Sincitial Respiratorio/epidemiología , Gripe Humana/epidemiología , Estudios Retrospectivos , Adulto , Femenino , Masculino , COVID-19/epidemiología , Persona de Mediana Edad , Niño , Adolescente , Lactante , Preescolar , Australia/epidemiología , SARS-CoV-2/aislamiento & purificación , Northern Territory/epidemiología , Anciano , Adulto Joven , Virus Sincitial Respiratorio Humano/aislamiento & purificación
20.
Artículo en Inglés | MEDLINE | ID: mdl-39165019

RESUMEN

Abstract: The Northern Territory (NT) has the highest rates of sexually transmitted infections (STI) in Australia; however, the local prevalence of Mycoplasma genitalium (M. genitalium) has not been previously determined. This study was designed to review M. genitalium detection, to determine the regional NT prevalence and macrolide resistance rates. In our study the NT background prevalence of M. genitalium is 13%, with the highest detection rates occurring in central Australia and in correctional facility inmates. Symptomatic patients attending sexual health clinics have a positivity rate of 12%, but very high macrolide resistance. The decision to screen for M. genitalium should be based on several factors, including the prevalence of the infection in the local population; the availability of effective treatments; and the potential benefits and risks of detection and therapy.


Asunto(s)
Infecciones por Mycoplasma , Mycoplasma genitalium , Humanos , Mycoplasma genitalium/aislamiento & purificación , Northern Territory/epidemiología , Infecciones por Mycoplasma/epidemiología , Infecciones por Mycoplasma/microbiología , Estudios Retrospectivos , Prevalencia , Masculino , Femenino , Adulto , Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Persona de Mediana Edad , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/microbiología , Adulto Joven , Macrólidos/farmacología
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