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1.
Nat Immunol ; 22(8): 1020-1029, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34312547

RESUMEN

T cell exhaustion is an induced state of dysfunction that arises in response to chronic infection and cancer. Exhausted CD8+ T cells acquire a distinct epigenetic state, but it is not known whether that chromatin landscape is fixed or plastic following the resolution of a chronic infection. Here we show that the epigenetic state of exhaustion is largely irreversible, even after curative therapy. Analysis of chromatin accessibility in HCV- and HIV-specific responses identifies a core epigenetic program of exhaustion in CD8+ T cells, which undergoes only limited remodeling before and after resolution of infection. Moreover, canonical features of exhaustion, including super-enhancers near the genes TOX and HIF1A, remain 'epigenetically scarred.' T cell exhaustion is therefore a conserved epigenetic state that becomes fixed and persists independent of chronic antigen stimulation and inflammation. Therapeutic efforts to reverse T cell exhaustion may require new approaches that increase the epigenetic plasticity of exhausted T cells.


Asunto(s)
Antígenos Virales/inmunología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Hepacivirus/inmunología , Hepatitis C Crónica/inmunología , Memoria Inmunológica/inmunología , 2-Naftilamina/uso terapéutico , Anilidas/uso terapéutico , Antivirales/uso terapéutico , Cromatina/metabolismo , Ciclopropanos/uso terapéutico , Epigénesis Genética/genética , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/tratamiento farmacológico , Proteínas del Grupo de Alta Movilidad/genética , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Lactamas Macrocíclicas/uso terapéutico , Prolina/análogos & derivados , Prolina/uso terapéutico , Ribavirina/uso terapéutico , Ritonavir/uso terapéutico , Sulfonamidas/uso terapéutico , Uracilo/análogos & derivados , Uracilo/uso terapéutico , Valina/uso terapéutico
2.
BMC Infect Dis ; 23(1): 28, 2023 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-36650474

RESUMEN

BACKGROUND: The distribution of the duration that clinical cases of COVID-19 occupy hospital beds (the 'length of stay') is a key factor in determining how incident caseloads translate into health system burden. Robust estimation of length of stay in real-time requires the use of survival methods that can account for right-censoring induced by yet unobserved events in patient progression (e.g. discharge, death). In this study, we estimate in real-time the length of stay distributions of hospitalised COVID-19 cases in New South Wales, Australia, comparing estimates between a period where Delta was the dominant variant and a subsequent period where Omicron was dominant. METHODS: Using data on the hospital stays of 19,574 individuals who tested positive to COVID-19 prior to admission, we performed a competing-risk survival analysis of COVID-19 clinical progression. RESULTS: During the mixed Omicron-Delta epidemic, we found that the mean length of stay for individuals who were discharged directly from ward without an ICU stay was, for age groups 0-39, 40-69 and 70 +, respectively, 2.16 (95% CI: 2.12-2.21), 3.93 (95% CI: 3.78-4.07) and 7.61 days (95% CI: 7.31-8.01), compared to 3.60 (95% CI: 3.48-3.81), 5.78 (95% CI: 5.59-5.99) and 12.31 days (95% CI: 11.75-12.95) across the preceding Delta epidemic (1 July 2021-15 December 2021). We also considered data on the stays of individuals within the Hunter New England Local Health District, where it was reported that Omicron was the only circulating variant, and found mean ward-to-discharge length of stays of 2.05 (95% CI: 1.80-2.30), 2.92 (95% CI: 2.50-3.67) and 6.02 days (95% CI: 4.91-7.01) for the same age groups. CONCLUSIONS: Hospital length of stay was substantially reduced across all clinical pathways during a mixed Omicron-Delta epidemic compared to a prior Delta epidemic, contributing to a lessened health system burden despite a greatly increased infection burden. Our results demonstrate the utility of survival analysis in producing real-time estimates of hospital length of stay for assisting in situational assessment and planning of the COVID-19 response.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Nueva Gales del Sur/epidemiología , COVID-19/epidemiología , Australia , Hospitales
3.
Intern Med J ; 53(5): 835-840, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37134258

RESUMEN

Prior to January 2022, only a single case of infection with Japanese encephalitis virus (JEV) had been reported on the Australian mainland, acquired in the northern extremity on Cape York. We report the clinical characteristics of the sentinel cluster of cases that confirmed the local acquisition of JEV in southern Australia along the Murray River bordering New South Wales and Victoria.


Asunto(s)
Culex , Virus de la Encefalitis Japonesa (Especie) , Encefalitis Japonesa , Animales , Humanos , Australia del Sur , Victoria
4.
Sex Abuse ; : 10790632231170818, 2023 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-37079276

RESUMEN

While there is a considerable body of literature on sexual aggression, we know much less about the violation of sexual boundaries within professional relationships. To address this knowledge gap, the characteristics of cases of sexual misconduct in the province of Quebec were extracted, based on a search of published disciplinary decisions between 1998 and 2020, using the legal databases CANLII and SOQUIJ. The search yielded 296 decisions including 249 male and 47 female members from 22 professional orders, and involving 470 victims. Results indicate that male professionals approaching mid-career accounted for a greater proportion of cases of sexual misconduct. Moreover, physical and mental health professionals were overrepresented in cases, as were female adult victims. Acts of sexual misconduct concerned mostly sexual touching and intercourse and occurred during consultations. Female professionals were more inclined to establish romantic and sexual relationships with clients than their male counterparts. Of the 92.0% of professionals found guilty of at least one count of sexual misconduct, two thirds eventually returned to practice. Following the guilty verdict, few faced rehabilitative measures. Recommendations are provided for the prevention of sexual recidivism and the accompaniment of victims of sexual misconduct throughout the disciplinary process.

5.
Eat Weight Disord ; 28(1): 37, 2023 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-37069446

RESUMEN

PURPOSE: Positive sexuality has received little empirical attention in relation to eating disorders. Two tendencies related to sexuality have been identified among women with anorexia nervosa (avoidance) and bulimia nervosa (disinhibition), but it is unclear if they also apply to women with binge eating episodes without compensatory behaviors. This study aimed at (1) exploring the sexual self-concept, functioning, and practices of women with binge eating episodes with or without comorbid restrictive and/or compensatory behaviors, considering past experiences of violence, and (2) verifying the presence of distinct profiles of sexual dispositions among this population. METHODS: In total, 253 women reporting recurrent episodes of loss of control related to food intake in the past 5 years, completed a web-based questionnaire. Descriptive and correlational analyses were conducted to outline participants' sexual self-concept, functioning, and practices and to examine the relationship between these factors. A two-step cluster analysis was also performed to determine whether participants presented distinct profiles of sexual dispositions. RESULTS: Participants were generally characterized by a negative sexual self-concept and poor sexual functioning. While a first subgroup of participants displayed a pattern of sexual difficulties and avoidance, a second subgroup had a positive sexual self-concept, better sexual functioning and a wider range of sexual practices. Subgroups did not differ relative to binge eating. CONCLUSIONS: Sexuality offers a platform for positive embodiment, which can lead to the improvement of body image and mind-body connection and may thus constitute an essential clinical target to improve treatment related to binge eating episodes. LEVEL OF EVIDENCE: Level II: The experimental study is a non-randomized controlled trial.


Asunto(s)
Trastorno por Atracón , Bulimia Nerviosa , Bulimia , Trastornos de Alimentación y de la Ingestión de Alimentos , Femenino , Humanos , Trastorno por Atracón/terapia , Bulimia Nerviosa/terapia , Autoimagen
6.
BMC Public Health ; 22(1): 1939, 2022 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-36261800

RESUMEN

BACKGROUND: There is increasing focus on moving populations towards healthier and more environmentally sustainable dietary patterns. The Australian Dietary Guidelines provide dietary patterns that promote health and wellbeing. It is unclear how these guidelines align with the more recently published global recommendations of the EAT-Lancet Planetary Health Reference Diet, and how Australian diets compare to both sets of recommendations. METHODS: Data from one 24-h recall collected for the 2011-13 National Nutrition and Physical Activity Survey were analysed for 5,920 adults aged 19-50 years. Subgroups of this population were identified by diet quality and lower or higher consumption of foods often considered to be environmentally intensive (higher animal meat and dairy foods) or associated with healthiness (higher vegetables and lower discretionary choices). Food group and nutrient composition of Australian diets were compared to diets modelled on the Australian Dietary Guidelines and Planetary Health Reference Diet. The environmental impacts of diets were estimated using an index of combined metrics. RESULTS: Compared with the Planetary Health Reference Diet, the Australian Dietary Guidelines contained more servings of the vegetable, dairy and alternatives, fruit, and discretionary choices. The amount of meat and alternatives was higher in the Planetary Health Reference Diet than Australian Dietary Guidelines due to the inclusion of more plant-based meat alternatives. The average Australian diet contained two to almost four times the Australian Dietary Guidelines and Planetary Health Reference Diet maximum recommended intake of discretionary choices, and provided inadequate amounts of the vegetables, cereals, unsaturated fats and meats and alternatives food groups, primarily due to lower intakes of plant-based alternatives. The average Australian diet also contained less dairy and alternatives than the Australian Dietary Guidelines. In the average Australian diet, red meat and poultry contributed 73% to the total servings of meat and alternatives compared to 33% and 10% for the Australian Dietary Guidelines and Planetary Health Reference Diet respectively. The modelled Australian Dietary Guidelines diet met the relevant nutrient reference value for all 22 nutrients examined, whereas the Planetary Health Reference Diet contained an inadequate amount of calcium. The environmental impact scores of the Planetary Health Reference Diet and Australian Dietary Guidelines were 31% and 46% lower than the average Australian diet. CONCLUSIONS: Significant changes are required for Australians' dietary intake to align more closely with national and global dietary recommendations for health and environmental sustainability.


Asunto(s)
Calcio , Promoción de la Salud , Animales , Humanos , Australia , Política Nutricional , Dieta , Verduras , Grasas Insaturadas , Ingestión de Energía
7.
J Youth Adolesc ; 51(3): 486-498, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34855025

RESUMEN

Positive psychosexual development in adolescence is crucial to sexual health. Evidence suggests that adolescent's psychosexual development is influenced by the sexual self-concept, relational skills, attitudes toward sexual pleasure, and sexual practices. To date, however, understanding of normative dispositions and experiences that positively shape adolescents' psychosexual development remains limited. The goal of the study was to provide a descriptive analysis of adolescents' perceptions of their sexual self, relational skills, and attitudes towards sexual pleasure as well as their sexual practices while considering age and gender differences. A Canadian sample of 1584 adolescents (49.7% girls, 49.4% boys and 0.9% gender diverse) aged 14 to 18 years old (M = 15.53, SD = 0.93) completed a self-reported questionnaire evaluating various aspects of sexuality and sexual practices. Results indicated that most youth are sexually active through autoerotic or partnered sexual practices, and that positive perceptions towards the sexual self, relational capacities and pleasure increase with age. Moreover, compared to girls, boys presented a more positive sexual self-concept, less positive perceptions of their relational skills and they were more likely to report autoerotic sexual practices. Cluster analysis supported classifying adolescents into the following profiles: positive, mildly positive, mildly negative and negative perception of the sexual self and sexuality. These profiles varied according to sexual practices, gender and age. This study provides further insight into general patterns and heterogeneity of adolescents' sexuality that are relevant for adapting sexuality education and sexual health intervention.


Asunto(s)
Placer , Conducta Sexual , Adolescente , Actitud , Canadá , Femenino , Humanos , Masculino , Percepción
8.
Transpl Infect Dis ; 23(2): e13510, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33217119

RESUMEN

Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) are an emerging threat in both solid organ and stem cell transplant recipients. Invasive CPE infections in transplant recipients are associated with a high mortality, often due to limited therapeutic options and antibacterial toxicities. One of the most therapeutically challenging group of CPE are the metallo-ß-lactamase (MBL)-producing Gram-negative bacteria, which are now found worldwide, and often need treatment with older, highly toxic antimicrobial regimens. Newer ß-lactamase inhibitors such as avibactam have well-established activity against certain carbapenemases such as Klebsiella pneumoniae carbapenemases (KPC), but have no activity against MBL-producing organisms. Conversely, aztreonam has activity against MBL-producing organisms but is often inactivated by other co-existing ß-lactamases. Here, we report four cases of invasive MBL-CPE infections in transplant recipients caused by IMP-4-producing Enterobacter cloacae who were successfully treated with a new, mechanism-driven antimicrobial combination of ceftazidime/avibactam with aztreonam. This novel antimicrobial combination offers a useful treatment option for high-risk patients with CPE infection, with reduced drug interactions and toxicity.


Asunto(s)
Compuestos de Azabiciclo , Aztreonam , Ceftazidima , Infecciones por Enterobacteriaceae , Humanos , Antibacterianos/uso terapéutico , Compuestos de Azabiciclo/uso terapéutico , Aztreonam/uso terapéutico , Proteínas Bacterianas , beta-Lactamasas , Ceftazidima/uso terapéutico , Combinación de Medicamentos , Enterobacter cloacae , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Receptores de Trasplantes
9.
Public Health Nutr ; 24(9): 2533-2541, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33092674

RESUMEN

OBJECTIVE: To understand how healthy menu labelling information is used by parents/caregivers and where it fits within predictors of healthy meal choices when eating out. DESIGN: Parents were recruited to complete a 15-min observational, online survey regarding their experiences and hypothetical choices when eating out with their child/ren. SETTING: Australia. PARTICIPANTS: Eligible participants had one or more child/ren aged between 2 and 12 years and attended cafes, restaurants, hotels and clubs (CRHC) for lunch or dinner at least four times a year. Of initial respondents (n 1802), 92·5 % provided complete and valid data. Participants were 84·7 % female, ranging from 18 to 68 years old. RESULTS: 98·3 % believed that healthier alternatives should be available for children in CRHC. For general food choices, health was a strong motivator (45·7 %); however, parents reported eating at CRHC mainly for pleasure or a treat (61·2 %) and being driven by children's taste preferences (85·9 %) when selecting menu items. 59·0 % of orders included a combination of healthy and traditional items. 42·0 % of the sample were influenced by the healthy choice (HC) labelling. Multiple regression revealed that, in addition to some demographic variables, the percent of HC ordered was positively associated with self-reported parent vegetable consumption, making food choices for the children for health reasons, familiarity with HC items and making order choices due to dietary needs and good nutrition. CONCLUSIONS: Despite a preference for availability of healthier children's menu choices in CRHC, menu labelling highlighting healthy options may have limited impact relative to child preferences.


Asunto(s)
Conducta de Elección , Preferencias Alimentarias , Adolescente , Adulto , Anciano , Actitud , Niño , Preescolar , Femenino , Etiquetado de Alimentos , Humanos , Masculino , Persona de Mediana Edad , Padres , Restaurantes , Adulto Joven
10.
J Infect Dis ; 221(7): 1135-1145, 2020 03 16.
Artículo en Inglés | MEDLINE | ID: mdl-31776569

RESUMEN

Initiation of antiretroviral therapy (ART) in early compared with chronic human immunodeficiency virus (HIV) infection is associated with a smaller HIV reservoir. This longitudinal analysis of 60 individuals who began ART during primary HIV infection (PHI) investigates which pre- and posttherapy factors best predict HIV DNA levels (a correlate of reservoir size) after treatment initiation during PHI. The best predictor of HIV DNA at 1 year was pre-ART HIV DNA, which was in turn significantly associated with CD8 memory T-cell differentiation (effector memory, naive, and T-bet-Eomes- subsets), CD8 T-cell activation (CD38 expression) and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) expression on memory T cells. No associations were found for any immunological variables after 1 year of ART. Levels of HIV DNA are determined around the time of ART initiation in individuals treated during PHI. CD8 T-cell activation and memory expansion are linked to HIV DNA levels, suggesting the importance of the initial host-viral interplay in eventual reservoir size.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , ADN Viral/sangre , Infecciones por VIH , Activación de Linfocitos/inmunología , Adulto , Antirretrovirales/uso terapéutico , Anticuerpos Antivirales/sangre , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Masculino , Carga Viral
11.
BMC Med ; 18(1): 265, 2020 08 21.
Artículo en Inglés | MEDLINE | ID: mdl-32825816

RESUMEN

BACKGROUND: New emerging infections have no known treatment. Assessing potential drugs for safety and efficacy enables clinicians to make evidence-based treatment decisions and contributes to overall outbreak control. However, it is difficult to launch clinical trials in the unpredictable environment of an outbreak. We conducted a bibliometric systematic review for the 2009 influenza pandemic to determine the speed and quality of evidence generation for treatments. This informs approaches to high-quality evidence generation in this and future pandemics. METHODS: We searched PubMed for all clinical data (including clinical trial, observational and case series) describing treatment for patients with influenza A(H1N1)pdm09 and ClinicalTrials.gov for research that aimed to enrol patients with the disease. RESULTS: Thirty-three thousand eight hundred sixty-nine treatment courses for patients hospitalised with A(H1N1)pdm09 were detailed in 160 publications. Most were retrospective observational studies or case series. Five hundred ninety-two patients received treatment (or placebo) as participants in a registered interventional clinical trial with results publicly available. None of these registered trial results was available during the timeframe of the pandemic, and the median date of publication was 213 days after the Public Health Emergency of International Concern ended. CONCLUSION: Patients were frequently treated for pandemic influenza with drugs not registered for this indication, but rarely under circumstances of high-quality data capture. The result was a reliance on use under compassionate circumstances, resulting in continued uncertainty regarding the potential benefits and harms of anti-viral treatment. Rapid scaling of clinical trials is critical for generating a quality evidence base during pandemics.


Asunto(s)
Antivirales/uso terapéutico , Ensayos de Uso Compasivo , Prescripción Inadecuada/prevención & control , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/tratamiento farmacológico , Uso Fuera de lo Indicado , Betacoronavirus , Bibliometría , COVID-19 , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Análisis Costo-Beneficio , Salud Global , Humanos , Gripe Humana/epidemiología , Pandemias , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/epidemiología , Proyectos de Investigación , SARS-CoV-2 , Resultado del Tratamiento
12.
Public Health Nutr ; 23(17): 3067-3080, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32690125

RESUMEN

OBJECTIVE: To examine core and discretionary food and beverage intake at eating occasions, and to explore the variation in consumption by age and gender in Australian adults and children. DESIGN: The study utilised one 24-h dietary recall with self-reported eating occasions from a nationally representative sample of Australians. Average servings of each food group for age and gender subpopulations were compared with the Australian Dietary Guidelines. The percentage contribution of each eating occasion to total daily food group intake and typical composition of eating occasions were described. Frequently consumed discretionary foods were reported for eating occasions by age and gender. SETTING: 2011-2012 Australian National Nutrition and Physical Activity Survey. PARTICIPANTS: 12 153 Australian people aged 2 years and above. RESULTS: Grains were consumed in equal proportions throughout the day across all age and gender subgroups, while remaining core food groups were unequally distributed, featuring more prominently at specific eating occasions. Children consumed two-thirds of their fruit intake as snacks, and up to three quarters of adults' vegetable and meat intake was consumed at dinner. Children consumed more of their discretionary intake at mid-meals, while adults consumed a greater proportion as part of a main meal. CONCLUSIONS: The present study provides a detailed understanding about when food groups are consumed, the 'typical' meal composition across the day, and how consumption patterns and compliance with dietary guidelines differ by age group and gender. These findings can assist in developing more specific nutrition messages which may help to achieve greater improvements in population dietary intake.


Asunto(s)
Dieta , Ingestión de Energía , Encuestas Nutricionales , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Australia , Niño , Preescolar , Ingestión de Alimentos , Conducta Alimentaria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estado Nutricional , Autoinforme , Adulto Joven
13.
PLoS Pathog ; 12(7): e1005661, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27415828

RESUMEN

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n = 122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression. Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/µl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed. Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants. Expression of 'exhaustion' or 'immune checkpoint' markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches.


Asunto(s)
Biomarcadores/análisis , Linfocitos T CD8-positivos/inmunología , Infecciones por VIH/inmunología , VIH-1 , Adulto , Antirretrovirales/uso terapéutico , Antígenos CD/análisis , Antígenos CD/biosíntesis , Antígenos CD/inmunología , Progresión de la Enfermedad , Femenino , Citometría de Flujo , Infecciones por VIH/tratamiento farmacológico , Receptor 2 Celular del Virus de la Hepatitis A/análisis , Receptor 2 Celular del Virus de la Hepatitis A/biosíntesis , Receptor 2 Celular del Virus de la Hepatitis A/inmunología , Humanos , Activación de Linfocitos/inmunología , Masculino , Receptor de Muerte Celular Programada 1/análisis , Receptor de Muerte Celular Programada 1/biosíntesis , Receptor de Muerte Celular Programada 1/inmunología , Proteína del Gen 3 de Activación de Linfocitos
15.
Curr HIV/AIDS Rep ; 11(1): 20-34, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24414166

RESUMEN

Increased life expectancy due to improved efficacy of cART has uncovered an increased risk of age-related morbidities in HIV+ individuals and catalyzed significant research into mechanisms driving these diseases. HIV infection increases the risk of non-communicable diseases common in the aged, including cardiovascular disease, neurocognitive decline, non-AIDS malignancies, osteoporosis, and frailty. These observations suggest that HIV accelerates immunological ageing, and there are many immunological similarities with the aged, including shortened telomeres, accumulation of senescent T cells and altered monocyte phenotype/function. However, the most critical similarity between HIV+ individuals and the elderly, which most likely underpins the heightened risk of non-communicable diseases, is chronic inflammation and associated immune activation. Here, we review the similarities between HIV+ individuals and the aged regarding the pathogenesis of inflammatory diseases, the current evidence for mechanisms driving these processes and discuss current and potential therapeutic strategies for addressing inflammatory co-morbidity in HIV+ infection.


Asunto(s)
Envejecimiento/inmunología , Infecciones por VIH/inmunología , Inflamación/inmunología , Enfermedades Cardiovasculares/inmunología , Enfermedades Cardiovasculares/virología , Comorbilidad , Infecciones por VIH/complicaciones , Humanos , Inmunidad Innata/inmunología , Enfermedades Metabólicas/inmunología , Enfermedades Metabólicas/virología
16.
AIDS ; 38(5): 679-688, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38133660

RESUMEN

OBJECTIVE: We present findings from a large cohort of individuals treated during primary HIV infection (PHI) and examine the impact of time from HIV-1 acquisition to antiretroviral therapy (ART) initiation on clinical outcomes. We also examine the temporal changes in the demographics of individuals presenting with PHI to inform HIV-1 prevention strategies. METHODS: Individuals who fulfilled the criteria of PHI and started ART within 3 months of confirmed HIV-1 diagnosis were enrolled between 2009 and 2020. Baseline demographics of those diagnosed between 2009 and 2015 (before preexposure prophylaxis (PrEP) and universal ART availability) and 2015-2020 (post-PrEP and universal ART availability) were compared. We examined the factors associated with immune recovery and time to viral suppression. RESULTS: Two hundred four individuals enrolled, 144 from 2009 to 2015 and 90 from 2015 to 2020; median follow-up was 33 months. At PHI, the median age was 33 years; 4% were women, 39% were UK-born, and 84% were MSM. The proportion of UK-born individuals was 47% in 2009-2015, compared with 29% in 2015-2020. There was an association between earlier ART initiation after PHI diagnosis and increased immune recovery; each day that ART was delayed was associated with a lower likelihood of achieving a CD4 + cell count more than 900 cells/µl [hazard ratio 0.99 (95% confidence interval, 95% CI 0.98-0.99), P  = 0.02) and CD4/CD8 more than 1.0 (hazard ratio 0.98 (95% CI 0.97-0.99). CONCLUSION: Early initiation of ART at PHI diagnosis is associated with enhanced immune recovery, providing further evidence to support immediate ART in the context of PHI. Non-UK-born MSM accounts for an increasing proportion of those with primary infection; UK HIV-1 prevention strategies should better target this group.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Seropositividad para VIH , VIH-1 , Minorías Sexuales y de Género , Masculino , Humanos , Femenino , Adulto , Infecciones por VIH/tratamiento farmacológico , Homosexualidad Masculina , Recuento de Linfocito CD4 , Seropositividad para VIH/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa
17.
Lancet Reg Health West Pac ; 47: 101103, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38953059

RESUMEN

Background: In Australia the incidence of HIV has declined steadily, yet sustained reduction of HIV transmission in this setting requires improved public health responses. As enhanced public health responses and prioritisation of resources may be guided by molecular epidemiological data, here we aimed to assess the applicability of these approaches in Victoria, Australia. Methods: A comprehensive collection of HIV-1 pol sequences from individuals diagnosed with HIV in Victoria, Australia, between January 1st 2000 and December 31st 2020 were deidentified and used as the basis of our assessment. These sequences were subtyped and surveillance drug resistance mutations (SDRMs) identified, before definition of transmission groups was performed using HIV-TRACE (0.4.4). Phylodynamic methods were applied using BEAST (2.6.6), assessing effective reproductive numbers for large groups, and additional demographic data were integrated to provide a high resolution view of HIV transmission in Victoria on a decadal time scale. Findings: Based on standard settings for HIV-TRACE, 70% (2438/3507) of analysed HIV-1 pol sequences were readily assigned to a transmission group. Individuals in transmission groups were more commonly males (aOR 1.50), those born in Australia (aOR 2.13), those with probable place of acquisition as Victoria (aOR 6.73), and/or those reporting injectable drug use (aOR 2.13). SDRMs were identified in 375 patients (10.7%), with sustained transmission of these limited to a subset of smaller groups. Informative patterns of epidemic growth, stabilisation, and decline were observed; many transmission groups showed effective reproductive numbers (R e ) values reaching greater than 4.0, representing considerable epidemic growth, while others maintained low R e values. Interpretation: This study provides a high resolution view of HIV transmission in Victoria, Australia, and highlights the potential of molecular epidemiology to guide and enhance public health responses in this setting. This informs ongoing discussions with community groups on the acceptability and place of molecular epidemiological approaches in Australia. Funding: National Health and Medical Research Council, Australian Research Council.

18.
Lancet Microbe ; 5(4): e317-e325, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38359857

RESUMEN

BACKGROUND: There has been high uptake of rapid antigen test device use for point-of-care COVID-19 diagnosis. Individuals who are symptomatic but test negative on COVID-19 rapid antigen test devices might have a different respiratory viral infection. We aimed to detect and sequence non-SARS-CoV-2 respiratory viruses from rapid antigen test devices, which could assist in the characterisation and surveillance of circulating respiratory viruses in the community. METHODS: We applied archival clinical nose and throat swabs collected between Jan 1, 2015, and Dec 31, 2022, that previously tested positive for a common respiratory virus (adenovirus, influenza, metapneumovirus, parainfluenza, rhinovirus, respiratory syncytial virus [RSV], or seasonal coronavirus; 132 swabs and 140 viral targets) on PCR to two commercially available COVID-19 rapid antigen test devices, the Panbio COVID-19 Ag Rapid Test Device and Roche SARS-CoV-2 Antigen Self-Test. In addition, we collected 31 COVID-19 rapid antigen test devices used to test patients who were symptomatic at The Royal Melbourne Hospital emergency department in Melbourne, Australia. We extracted total nucleic acid from the device paper test strips and assessed viral recovery using multiplex real-time PCR (rtPCR) and capture-based whole genome sequencing. Sequence and genome data were analysed through custom computational pipelines, including subtyping. FINDINGS: Of the 140 respiratory viral targets from archival samples, 89 (64%) and 88 (63%) were positive on rtPCR for the relevant taxa following extraction from Panbio or Roche rapid antigen test devices, respectively. Recovery was variable across taxa: we detected influenza A in nine of 18 samples from Panbio and seven of 18 from Roche devices; parainfluenza in 11 of 20 samples from Panbio and 12 of 20 from Roche devices; human metapneumovirus in 11 of 16 from Panbio and 14 of 16 from Roche devices; seasonal coronavirus in eight of 19 from Panbio and two of 19 from Roche devices; rhinovirus in 24 of 28 from Panbio and 27 of 28 from Roche devices; influenza B in four of 15 in both devices; and RSV in 16 of 18 in both devices. Of the 31 COVID-19 devices collected from The Royal Melbourne Hospital emergency department, 11 tested positive for a respiratory virus on rtPCR, including one device positive for influenza A virus, one positive for RSV, four positive for rhinovirus, and five positive for SARS-CoV-2. Sequences of target respiratory viruses from archival samples were detected in 55 (98·2%) of 56 samples from Panbio and 48 (85·7%) of 56 from Roche rapid antigen test devices. 98 (87·5%) of 112 viral genomes were completely assembled from these data, enabling subtyping for RSV and influenza viruses. All 11 samples collected from the emergency department had viral sequences detected, with near-complete genomes assembled for influenza A and RSV. INTERPRETATION: Non-SARS-CoV-2 respiratory viruses can be detected and sequenced from COVID-19 rapid antigen devices. Recovery of near full-length viral sequences from these devices provides a valuable opportunity to expand genomic surveillance programmes for public health monitoring of circulating respiratory viruses. FUNDING: Australian Government Medical Research Future Fund and Australian National Health and Medical Research Council.


Asunto(s)
COVID-19 , Gripe Humana , Metapneumovirus , Infecciones por Paramyxoviridae , Virus Sincitial Respiratorio Humano , Humanos , COVID-19/diagnóstico , SARS-CoV-2/genética , Gripe Humana/diagnóstico , Prueba de COVID-19 , Australia , Metapneumovirus/genética , Virus Sincitial Respiratorio Humano/genética , Secuenciación Completa del Genoma
19.
Aust J Gen Pract ; 52(5): 275-280, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37149766

RESUMEN

BACKGROUND: Japanese encephalitis virus (JEV) is a mosquito-borne arbovirus endemic to the Asia-Pacific that causes high morbidity and mortality in those who develop symptomatic disease. Prior to 2021, only five locally acquired cases had been detected in Australia, all in northern Australia. Following a sentinel case in 2021, widespread dissemination of JEV was detected in northern and south-eastern Australia, accompanied by an increase in locally acquired cases, which have been detected as far south as Victoria. This expansion has occurred in the setting of warmer and wetter conditions under the influence of climate change. OBJECTIVE: To provide Australian general practitioners (GPs) an overview of JEV, given its recent expansion, and the potential for sustained endemicity. DISCUSSION: As the distribution of JEV expands under the influence of climate change, Australian GPs need to be familiar with this condition, especially those practicing in rural areas and where detections have occurred.


Asunto(s)
Virus de la Encefalitis Japonesa (Especie) , Encefalitis Japonesa , Animales , Humanos , Cambio Climático , Encefalitis Japonesa/diagnóstico , Encefalitis Japonesa/epidemiología , Victoria
20.
J Sex Res ; : 1-11, 2023 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-37307397

RESUMEN

Adolescence is a crucial period for the development of the sexual self-concept. While existing research shows that adolescents' sexual self-concept varies, few studies have examined its relation with psychosocial competencies such as the general self-concept, interpersonal skills, and self-control capacities. The objective of this study was to examine the association between dimensions of the sexual self-concept (sexual self- and body esteem, self-efficacy, and anxiety) and psychosocial competencies among Canadian adolescents. Self-reported data from 1584 adolescents aged between 14 and 18 years (49.7% girls) were analyzed using path analysis. Results show that adolescents whose general self-concept was characterized by more internally consistent self-beliefs and greater self-worth, and who perceived their interpersonal skills as more developed, displayed higher sexual self- and body esteem, higher sexual self-efficacy, and lower sexual anxiety. Self-control capacities were positively correlated with sexual body-esteem and negatively correlated with sexual anxiety. These associations were, however, minimal and, when significant, exhibited a counterintuitive relationship with the sexual self-concept in the path model. Age, gender and sexual experience did not moderate these associations. Findings from the study highlight the need to pursue research on the interface between sexuality and psychosocial functioning to increase current understanding of adolescent development.

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