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BACKGROUND: Coronavirus-like particles (CoVLP) that are produced in plants and display the prefusion spike glycoprotein of the original strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are combined with an adjuvant (Adjuvant System 03 [AS03]) to form the candidate vaccine. METHODS: In this phase 3, multinational, randomized, placebo-controlled trial conducted at 85 centers, we assigned adults (≥18 years of age) in a 1:1 ratio to receive two intramuscular injections of the CoVLP+AS03 vaccine or placebo 21 days apart. The primary objective of the trial was to determine the efficacy of the CoVLP+AS03 vaccine in preventing symptomatic coronavirus disease 2019 (Covid-19) beginning at least 7 days after the second injection, with the analysis performed after the detection of at least 160 cases. RESULTS: A total of 24,141 volunteers participated in the trial; the median age of the participants was 29 years. Covid-19 was confirmed by polymerase-chain-reaction assay in 165 participants in the intention-to-treat population; all viral samples that could be sequenced contained variants of the original strain. Vaccine efficacy was 69.5% (95% confidence interval [CI], 56.7 to 78.8) against any symptomatic Covid-19 caused by five variants that were identified by sequencing. In a post hoc analysis, vaccine efficacy was 78.8% (95% CI, 55.8 to 90.8) against moderate-to-severe disease and 74.0% (95% CI, 62.1 to 82.5) among the participants who were seronegative at baseline. No severe cases of Covid-19 occurred in the vaccine group, in which the median viral load for breakthrough cases was lower than that in the placebo group by a factor of more than 100. Solicited adverse events were mostly mild or moderate and transient and were more frequent in the vaccine group than in the placebo group; local adverse events occurred in 92.3% and 45.5% of participants, respectively, and systemic adverse events in 87.3% and 65.0%. The incidence of unsolicited adverse events was similar in the two groups up to 21 days after each dose (22.7% and 20.4%) and from day 43 through day 201 (4.2% and 4.0%). CONCLUSIONS: The CoVLP+AS03 vaccine was effective in preventing Covid-19 caused by a spectrum of variants, with efficacy ranging from 69.5% against symptomatic infection to 78.8% against moderate-to-severe disease. (Funded by Medicago; ClinicalTrials.gov number, NCT04636697.).
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Adjuvantes de Vacinas , Vacinas contra COVID-19 , COVID-19 , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/efeitos adversos , Adjuvantes Imunológicos/uso terapêutico , Adjuvantes de Vacinas/administração & dosagem , Adjuvantes de Vacinas/efeitos adversos , Adjuvantes de Vacinas/uso terapêutico , Adulto , Anticorpos Antivirais , COVID-19/genética , COVID-19/prevenção & controle , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/uso terapêutico , Método Duplo-Cego , Humanos , Injeções Intramusculares , SARS-CoV-2/genética , VacinaçãoRESUMO
The National Reference Laboratory in Clinical Mycology of Argentina conducted a retrospective review of human coccidioidomycosis cases diagnosed by the National Mycology Laboratory Network of Argentina between 2010 and 2022 to determine the burden of the disease in the country. A total of 100 human coccidioidomycosis cases were documented, with a higher prevalence in male patients (male-to-female ratio of 1.9:1), with a median age of 41 years. Comparing the number of cases between two 10-year periods (2000-2009 and 2010-2019), the increase was 36.51% (from 63 to 86 cases). Among the 100 recorded cases, 79 tested positive using the double immunodiffusion test. Spherules were observed in 19 cases through histopathology or direct microscopic examination and the fungus was isolated in 39 cases. Thirty-six isolates were identified as Coccidioides posadasii through partial sequencing of the Ag2/PRA gene. Catamarca province had the highest number of cases, comprising 64% of the total, with an incidence rate above 1.0-2.5/100,000 inhabitants until 2018. However, there has been a recent downward trend in the region from 2018 to 2022. It is concerning that more than half of diagnosed cases were chronic pulmonary or disseminated forms, indicating a lack of early disease detection. To rectify this issue, it is imperative to conduct targeted training programs for healthcare personnel and enhance public awareness within the endemic area. This will contribute to a better understanding of the true burden of coccidioidomycosis and enable the implementation of appropriate sanitary control measures.
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Coccidioides , Coccidioidomicose , Humanos , Coccidioidomicose/epidemiologia , Coccidioidomicose/microbiologia , Argentina/epidemiologia , Masculino , Feminino , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Coccidioides/genética , Coccidioides/isolamento & purificação , Idoso , Adulto Jovem , Prevalência , Incidência , Adolescente , Criança , Idoso de 80 Anos ou mais , Pré-EscolarRESUMO
Immunosuppressed patients, transplant recipients, and those with acute or chronic respiratory disease are at increased risk for invasive fungal infections in Argentina. Although the national public system guarantees universal access to health care for all citizens, little is known about the quality of available diagnostic and treatment armamentaria for invasive fungal infections in the country. Between June and August 2022, infectious disease clinicians from each of the 23 provinces and the Autonomous City of Buenos Aires were contacted to describe local access to fungal diagnostic tools and antifungal agents. The information collected included different aspects such as hospital characteristics, patients admitted and wards, access to diagnostic tools, estimated infection incidence, and treatment capacity. Thirty responses were collected from facilities throughout Argentina. Most institutions were governmental (77%). A mycology department was available in 83% of them. Histopathology was available in almost 93% of the sites, while automated methods and galactomannan tests were available in 57%, each; 53% of the sites had access to MALDI-TOF-MS through regional reference laboratories, and PCR was present in 20% of the sites. Susceptibility testing was available in 63% of the laboratories. Candida spp. (24%), Cryptococcus spp. (20%), Aspergillus spp. (18%), and Histoplasma spp. (16%) were described as the main pathogens. Fluconazole was the only antifungal agent available in all institutions. This was followed by amphotericin B deoxycholate (83%) and itraconazole (80%). If an antifungal agent was not available onsite, then 60% of the patients could receive adequate antifungal treatment within the first 48 h upon request. Although there are no significant differences in access to diagnostic and clinical management of invasive fungal infections among the Argentinean centres studied, national awareness-raising initiatives led by policymakers could help to improve their general availability.
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Antifúngicos , Infecções Fúngicas Invasivas , Animais , Antifúngicos/uso terapêutico , Argentina/epidemiologia , Fluconazol , Itraconazol , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/veterináriaRESUMO
BACKGROUND: Trichosporon fungaemia (TF) episodes have increased in recent years and mortality rates remain high despite the advances in the management of sepsis. New concepts about its clinical course, treatment and microbiology need to be investigated for the better management of this infection. OBJECTIVES: To describe the aetiology, natural history, clinical management and prognostic factors of TF. METHODS: TF episodes documented between 2005 and 2018 in 23 South American centres were retrospectively investigated by using a standard clinical form. Molecular identification, antifungal susceptibility testing and biofilm production were also performed. RESULTS: Eighty-eight TF episodes were studied. Patients had several underlying conditions, including haematological diseases (47.7%), post-operative status (34%), solid organ transplants (n = 7, 7.9%), among others. Seventy-three (82.9%) patients had a central venous catheter (CVC) at TF diagnosis. The 30 day mortality rate was 51.1%. Voriconazole-based therapy was given to 34 patients (38.6%), with a 30 day mortality rate of 38.2%. Multivariate predictors of 30 day mortality were age (OR 1.036), mechanical ventilation (OR 8.25) and persistent neutropenia (OR 9.299). CVC removal was associated with over 75% decreased risk of 30 day mortality (OR 0.241). Microbiological analyses revealed that 77.7% of the strains were identified as Trichosporon asahii, and voriconazole showed the strongest in vitro activity against Trichosporon spp. Most of the strains (63%) were considered medium or high biofilm producers. CONCLUSIONS: Older age, mechanical ventilation and persistent neutropenia were associated with poor prognosis. CVC may play a role in the pathogenicity of TF and its removal was associated with a better prognosis.
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Fungemia , Trichosporon , Idoso , Antifúngicos/uso terapêutico , Basidiomycota , Fungemia/tratamento farmacológico , Fungemia/epidemiologia , Humanos , Testes de Sensibilidade Microbiana , Prognóstico , Estudos Retrospectivos , Trichosporon/genéticaRESUMO
BACKGROUND: Neuroscience and neurotechnology are transforming stroke rehabilitation. Robotic devices, in addition to telerehabilitation, are increasingly being used to train the upper limbs after stroke, and their use at home allows us to extend institutional rehabilitation by increasing and prolonging therapy. The aim of this study is to assess the usability of the MERLIN robotic system based on serious games for upper limb rehabilitation in people with stroke in the home environment. METHODS: 9 participants with a stroke in three different stages of recovery (subacute, short-term chronic and long-term chronic) with impaired arm/hand function, were recruited to use the MERLIN system for 3 weeks: 1 week training at the Maimonides Biomedical Research Institute of Cordoba (IMIBIC), and 2 weeks at the patients' homes. To evaluate usability, the System Usability Scale (SUS), Adapted Intrinsic Motivation Inventory (IMI), Quebec User Evaluation of Satisfaction with assistive Technology (QUEST), and the ArmAssist Usability Assessment Questionnaire were used in the post-intervention. Clinical outcomes for upper limb motor function were assessed pre- and post-intervention. RESULTS: 9 patients participated in and completed the study. The usability assessment reported a high level of satisfaction: mean SUS score 71.94 % (SD = 16.38), mean QUEST scale 3.81 (SD = 0.38), and mean Adapted IMI score 6.12 (SD = 1.36). The results of the ArmAssist Questionnaire showed an average of 6 out of 7, which indicates that MERLIN is extremely intuitive, easy to learn and easy to use. Regarding clinical assessment, the Fugl-Meyer scores showed moderate improvements from pre- to post-intervention in the total score of motor function (p = 0.002). There were no significant changes in the Modified Ashworth scale outcomes (p = 0.169). CONCLUSIONS: This usability study indicates that home-based rehabilitation for upper limbs with the MERLIN system is safe, useful, feasible and motivating. Telerehabilitation constitutes a major step forward in the use of intensive rehabilitation at home. Trial registration ClinicalTrials.gov, NCT04405609. Registered 06 January 2020-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04405609.
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Robótica/instrumentação , Reabilitação do Acidente Vascular Cerebral/instrumentação , Telerreabilitação/instrumentação , Jogos de Vídeo , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia por Exercício/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Recuperação de Função Fisiológica , Reabilitação do Acidente Vascular Cerebral/métodos , Extremidade Superior/fisiopatologia , Interface Usuário-ComputadorRESUMO
Candidemia is the most frequent invasive mycosis in hospitalized patients worldwide. Fungal infection in central nervous system is a life-threatening complication which aggravates patients' prognosis. This article summarizes relevant aspects on the clinical characteristics of this pathology, mechanisms of fungus invasion, local immune response to Candida albicans and the impact of genetic defects on innate immune receptors that increase susceptibility to the acquisition of this form of mycosis.
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Candidíase Invasiva , Infecções do Sistema Nervoso Central , Candida albicans , Candidíase Invasiva/diagnóstico , HumanosRESUMO
Equine embryos develop in vitro in the presence of high glucose concentrations, but little is known about their requirements for development. We evaluated the effect of glucose concentrations in medium on blastocyst development after ICSI. In experiment 1, there were no significant differences in rates of blastocyst formation among embryos cultured in our standard medium (DMEM/F-12), which contained >16âmM glucose, and those cultured in a minimal-glucose embryo culture medium (<1âmM; Global medium, GB), with either 0 added glucose for the first 5 days, then 20âmM (0-20) or 20âmM for the entire culture period (20-20). In experiment 2, there were no significant differences in the rates of blastocyst development (31-46%) for embryos cultured in four glucose treatments in GB (0-10, 0-20, 5-10, or 5-20). Blastocysts were evaluated by immunofluorescence for lineage-specific markers. All cells stained positively for POU5F1. An inner cluster of cells was identified that included presumptive primitive endoderm cells (GATA6-positive) and presumptive epiblast (EPI) cells. The 5-20 treatment resulted in a significantly lower number of presumptive EPI-lineage cells than the 0-20 treatment did. GATA6-positive cells appeared to be allocated to the primitive endoderm independent of the formation of an inner cell mass, as was previously hypothesized for equine embryos. These data demonstrate that equine blastocyst development is not dependent on high glucose concentrations during early culture; rather, environmental glucose may affect cell allocation. They also present the first analysis of cell lineage allocation in in vitro-fertilized equine blastocysts. These findings expand our understanding of the factors that affect embryo development in the horse.
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Blastocisto/efeitos dos fármacos , Linhagem da Célula/efeitos dos fármacos , Linhagem da Célula/fisiologia , Desenvolvimento Embrionário/efeitos dos fármacos , Glucose/administração & dosagem , Animais , Blastocisto/citologia , Desenvolvimento Embrionário/fisiologia , CavalosRESUMO
Leucocytozoon infection has been observed to impact the reproductive ecology and physiology of avian hosts, but its influence on nestling survival remains unclear. We investigated the effect of Leucocytozoon infection intensity, determined through triplicate PCR sample analyses, on the survival of 256 boreal owl (Aegolius funereus) nestlings during an 8-yr study. Contrary to our expectations, the survival probability of boreal owl nestlings was not influenced by their Leucocytozoon infection intensity. Nestling age and Leucocytozoon infection intensity in male and female parents also did not impact nestling survival. Instead, food abundance and hatching order were the key factors influencing nestling survival. Additionally, we observed a significantly higher Leucocytozoon infection intensity in male parents compared to female parents and nestlings. We suggest a distinct division of parental roles may lead females and nestlings staying within the nest boxes (cavities) to experience lower exposure to potential vectors transmitting blood parasites than their male counterparts. Our study shows that Leucocytozoon disease may not be lethal for boreal owl chicks, exhibiting a below-average infection intensity compared to their male parents.
La infección por Leucocytozoon no influye en la supervivencia de los polluelos de mochuelo boreal Aegolius funereus. Se ha observado que la infección por Leucocytozoon afecta la ecología y fisiología reproductiva de las aves hospedadoras, pero su influencia en la supervivencia de los polluelos aún no está completamente determinada. Se investigó el efecto de la intensidad de la infección por Leucocytozoon, determinada mediante análisis de muestras de PCR por triplicado, sobre la supervivencia de 256 polluelos de mochuelo boreal (Aegolius funereus) durante un estudio de ocho años. Contrariamente a nuestras expectativas, la probabilidad de supervivencia de los polluelos de mochuelo boreal no se vio influenciada por la intensidad de la infección por Leucocytozoon. La edad de los polluelos y la intensidad de la infección por Leucocytozoon en los padres machos y hembras tampoco afectaron la supervivencia de los polluelos. En cambio, la abundancia de alimento y el orden de eclosión fueron los principales factores que influyeron en la supervivencia de los polluelos. Además, se observó una intensidad de infección por Leucocytozoon significativamente mayor en los padres machos en comparación con las hembras y los polluelos. Se sugiere que una clara división de los roles parentales puede llevar a que las hembras y los polluelos que permanecen dentro de las cajas nido (cavidades) experimenten una menor exposición a vectores potenciales que transmitan parásitos sanguíneos en comparación con los individuos adultos masculinos. Nuestro estudio muestra que la enfermedad de Leucocytozoon puede no ser letal para los polluelos de mochuelo boreal, ya que exhiben una intensidad de infección por debajo del promedio en comparación con sus padres machos.
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Doenças das Aves , Estrigiformes , Animais , Estrigiformes/fisiologia , Masculino , Feminino , Doenças das Aves/parasitologia , Doenças das Aves/mortalidade , Microsporidiose/veterinária , Haemosporida/fisiologiaRESUMO
Trigger finger causes pain and a persistent functional limitation of the hand, which can lead to permanent blockage of the flexor tendon. Ultrasonography-guided percutaneous release has been widely reported as a successful technique for trigger finger involving the A1 pulley. This article describes for the first time the use of this technique in an unusual location, the A3 pulley of the fifth finger. A 71-year-old patient presented with a 3-month history of pain and blockage in the fifth finger of the right hand and was diagnosed with a grade III trigger finger, according to the Froimson scale. We performed an ultrasonography-guided percutaneous release technique on the A3 pulley to release the flexor tendon of the fifth finger. Ultrasonography-guided percutaneous polectomy to treat trigger finger in the A1 pulley is an effective alternative treatment to surgery and even has certain advantages over it. The anatomical similarity between the A1 and A3 pulleys was the key factor that supported the use of this technique in this clinical case. Based on past experience in similar cases, we conclude that ultrasonography-guided percutaneous polectomy of the A3 pulley of the fifth finger was a surgical technique which could lead to a satisfactory outcome in the treatment of this condition.
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Dedo em Gatilho , Humanos , Idoso , Dedo em Gatilho/diagnóstico por imagem , Dedo em Gatilho/cirurgia , Ultrassonografia , Dedos/diagnóstico por imagem , Dedos/cirurgia , Tendões/diagnóstico por imagem , Tendões/cirurgia , DorRESUMO
Antifungal stewardship is a critical component of healthcare management that focuses on optimizing the use of antifungal medications to improve patient outcomes, minimize resistance, and reduce healthcare costs. In resource-limited settings, the prevalence of fungal infections remains a significant health concern, often exacerbated by factors such as compromised immune systems, inadequate diagnostic capabilities, and limited access to antifungal agents. This paper reviews the current state of antifungal stewardship practices in developing countries, addressing the unique socioeconomic and healthcare landscape.
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Invasive candidiasis encompassing Candida bloodstream infections and deep-seated candidiasis can become a persistent health problem. These infections are caused by Candida species and have high morbidity and mortality rates. Species distribution, access to diagnosis, treatment and mortality are different around the world. The mortality rate is high in South America (30-70%), and Candida albicans is the most prevalent species in this region. However, a global epidemiological shift to non-albicans species has been observed. In this group, C. parapsilosis is the species most frequently detected, followed by C. tropicalis, and at a slower rate, C. glabrata, which has also increased, in addition to the emerging C. auris, resistance to several drugs. This article summarizes relevant aspects of candidemia pathogenesis, such as the mechanisms of fungal invasion, immune response, and the impact of genetic defects that increase host susceptibility to developing the infection. We also discuss relevant aspects of treatment and future challenges in South America.
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Vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis (RVVC) are two forms of a disease caused by Candida spp. ß-defensin (BD) is one of the most important families of antimicrobial peptides in the female genital tract and includes molecules that exert essential local functions as antimicrobial and PMN chemoattractant peptides. However, the information on their role during murine and human VVC and RVVC is limited. Thus, we analyzed the behavior and contribution of BD1 to the local response in a VVC mice model and the local cytokine profile and human BD1 and BD3 expression in cervicovaginal lavage from patients with VVC and RVVC. We demonstrated that, in patients with RVVC BD1, mRNA and protein expression were severely diminished and that the aspartate proteinase and lipase secreted by C. albicans are involved in that decrease. This study provides novel information about the pathogenesis of VVC and describes a highly efficient C. albicans escape strategy for perpetuating the infection; these results may contribute to the development of new or combined treatment approaches.
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UNLABELLED: In March 2009, there was an outbreak of respiratory illness, later identified as caused by Influenza A (H1N1); the affected patients can develop severe lower respiratory infections. OBJECTIVE: To describe the characteristics of 14 patients admitted to Hospital Córdoba diagnosed with H1N1 Influenza-associated pneumonia during July and August of 2009. MATERIAL AND METHODS: We analyzed patients admitted between 26/06/09 and 08/09/2009 with diagnosis of community-acquired pneumonia. All patients were conducted laboratory, chest X-ray, blood and nasal swab for viral isolation by polymerase chain reaction (real-time RT-PCR), beginning treatment with sulbactam ampicillin, clarithromycin, and oseltamivir. RESULTS: The number of patients studied was 44 patients, in 14 patients was confirmed the diagnosis of influenza by RT-PCR, the median age was 44 years (range 18 to 81 years) and 9 (64%) were female. The average time between onset of symptoms and medical consultation was 5 days and the average hospital stay was 6 days. CLINICAL SYMPTOMS: fever over 38 C, 13 patients (92%), dry cough, 4 patients (28%), productive cough, 9 (64 %), headache and myalgia: 6. Radiological presentation 10 (72 %) patients had bilateral involvement, both bases, and two or more quadrants involved in the chest X-ray. Co morbilities: one patient had heart disease and one patient had COPD. RISK FACTORS: 3 patients were alcoholic, 4 patients were smokers, and 2 postpartum. A single patient with H1N1 required mechanical ventilation and died. CONCLUSION: pneumonia influenza (H1N1) can cause bilateral commitment, affect healthy patients at a younger age.
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Vírus da Influenza A Subtipo H1N1 , Influenza Humana/diagnóstico , Pneumonia Viral/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Argentina , Infecções Comunitárias Adquiridas/diagnóstico , Estudos Transversais , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Masculino , Pessoa de Meia-Idade , Distribuição por Sexo , Adulto JovemRESUMO
Hospital antibiotic use in Argentina has not been described. We present results of point prevalence surveys on antibiotic use conducted in 109 Argentinian hospitals in November 2018 and submitted to the National Program of Epidemiology and Control of Hospital-Acquired Infections, and we discuss potential areas for improvement.
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Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecção Hospitalar/tratamento farmacológico , Uso de Medicamentos/estatística & dados numéricos , Hospitais/estatística & dados numéricos , Adulto , Argentina/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Infecção Hospitalar/epidemiologia , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
The number of fungal infections at any given time in Argentina is not known. Here we estimate the burden of serious fungal infections in Argentina for the first time. Specific population statistics were searched from multiple sources, local literature was identified, and estimates made. Some additional data were sourced from the Ministry of Health, the Global Initiative for Asthma (GINA) program, and national haematology and transplant societies. Argentina has a population of 43.8 million, with 25% of this total being children under 15 years. The predicted candidemia annual incidence is 2193 cases, with 50% occurring in the ICU. At a 6% prevalence rate, an estimated 593,695 women suffer from recurrent vulvovaginal candidiasis. Invasive aspergillosis is relatively common because of high smoking and chronic obstructive pulmonary disease (COPD) rates, with 268 cases in immunocompromised patients and another 1938 in the 168,000 COPD patients admitted to hospital. Asthma is also common, affecting 14% of adults, and so allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS) are major problems. An estimated 432 cases of cryptococcal meningitis (CM)-90% of them in AIDS patients-and 1177 cases of Pneumocystis pneumonia (PCP) occur each year. The estimated annual case number of disseminated histoplasmosis is 404 in AIDS patients, almost as frequent as CM. Paracoccidioidomycosis annual incidence is estimated at 219, and coccidioidomycosis at 16 cases. At least 881,023 people (>2.01%) in Argentina are affected by a serious fungal disease annually, with considerable morbidity and mortality.
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Candida albicans is the prevalent etiological agent in acute vulvovaginal infection and the most severe chronic condition known as recurrent vulvovaginal candidiasis (VVC). A critical role of local innate immunity in defense and pathogenesis of vaginal infection by Candida is proposed. The fungal recognition by the innate immune receptor is an essential step for the induction of local responses including cytokines and antimicrobial peptides (AMPs) production for host protection. Using TLR2-deficient mice, we characterized the early innate immune response during VVC. Intravaginal challenge of TLR2-/- mice with C. albicans demonstrated that in response to the initial massive penetration, a strong local inflammatory reaction with recruitment of polymorphonuclear neutrophils was developed. Both interleukin 1ß (IL1ß)-regarded as the hallmark of VVC immunopathogenesis-and IL6 were increased in vaginal lavage. Murine beta defensin 1 (mBD1), a constitutive AMP with fungicidal and chemotactic activity, was significantly upregulated in wild type (WT) animals in response to infection. Interestingly, in the absence of TLR2 recognition, levels of mBD1 RNA more than twice higher than those in WT infected animals were observed. Interestingly, our results demonstrate that TLR2 signaling is important to control the fungal burden in the vaginal tract. These finding provide new evidence about the role of this innate receptor during VVC.
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Candidíase Vulvovaginal/genética , Receptor 2 Toll-Like/metabolismo , Animais , Candida albicans , Candidíase Vulvovaginal/microbiologia , Citocinas/genética , Citocinas/metabolismo , Feminino , Predisposição Genética para Doença , Inflamação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptor 2 Toll-Like/genéticaRESUMO
Vulvovaginal candidiasis is an old disease that, even in a modern world, continues to have a high incidence. Despite the therapeutic advances, treatments are not always effective, and our understanding of the pathogenesis of this fungal infection is still incomplete. A discussion is presented in this article on the most significant developments related to the fungal virulence factors, the role of the immunological mechanisms involved in the vaginal protection, and the genetic alterations that confer susceptibility to the recurrent form of this mycosis. Current treatments, the use of new agents with antifungal activity, as well as the development of strategies, such as vaccination, are approached in the context of the complex scenario that governs the interactions between Candida and its host.
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Candidíase Vulvovaginal , Antifúngicos/uso terapêutico , Biofilmes , Candida/imunologia , Candida/isolamento & purificação , Candida/patogenicidade , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/genética , Candidíase Vulvovaginal/imunologia , Candidíase Vulvovaginal/microbiologia , Adesão Celular , Suscetibilidade a Doenças , Drogas em Investigação/uso terapêutico , Estrogênios/fisiologia , Feminino , Vacinas Fúngicas , Interações Hospedeiro-Patógeno , Humanos , Imunidade Inata , Infecções Oportunistas/imunologia , Infecções Oportunistas/microbiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Especificidade da Espécie , Vagina/imunologia , Vagina/microbiologia , VirulênciaRESUMO
Transfer of donor oocytes to the oviducts of inseminated recipient mares (oocyte transfer, OT) presents a valuable method for production of foals from otherwise infertile mares. Little information is available, however, on factors affecting success of OT in a clinical setting. We report the findings over three breeding seasons in a commercial OT program developed at an equine embryo transfer center in Argentina. Overall, 25 mares were enrolled, and 197 follicle aspiration procedures were performed. The average mare age was 23 years. Follicle aspiration was performed with a needle placed through the flank; the oocyte recovery rate per follicle aspirated was 149 of 227 (66%). Induction of donor ovulation with deslorelin + hCG resulted in a significantly higher oocyte recovery rate than did induction with deslorelin alone (75% vs. 58%). There was no significant effect of mare age (17-20, 21-24, or 25-27 years) on oocyte recovery rate. Twelve oocytes were degenerating or lost during handling; transfer of the remaining 137 oocytes resulted in 42 pregnancies (31%) at 14 days. Of these, 32 (23% per transfer) went on to produce a foal or ongoing pregnancy. Transfer of oocytes recovered with a compact cumulus, without donor follicle induction, or less than 20 hours after induction was associated with a significantly reduced pregnancy rate (1/16, 6%), as was use of noncycling, hormone-treated recipients (2/22, 9%). To evaluate management factors affecting pregnancy rate, noncycling, hormone-treated recipients were disregarded, and only procedures using mature (expanded cumulus) oocytes recovered and transferred on the standard schedule (n = 99) were included. Mare age did not significantly affect rates of pregnancy or pregnancy loss. Similar pregnancy rates were obtained using recipients inseminated from 1 to 27 hours before transfer. Counterintuitively, insemination of recipients immediately (1-2 hours) after aspiration of the recipient follicle was associated with a high pregnancy rate (10/12, 83%). There was no significant effect on pregnancy rate of donor induction agent, the time the oocyte was in culture (2-20 hours) before transfer, time from recipient insemination to transfer, or total time from donor induction to transfer (32-45 hours). These findings establish that OT is robust, in that it is effective over a wide variation in timing of the different components involved, and can be successfully developed in a private embryo transfer practice.
Assuntos
Cruzamento/métodos , Cavalos/fisiologia , Doação de Oócitos/veterinária , Oócitos/transplante , Fatores Etários , Animais , Feminino , Gravidez , Resultado da Gravidez , Taxa de GravidezRESUMO
Equine intracytoplasmic sperm injection (ICSI) is being used clinically for foal production, but little information is available on factors affecting the efficiency of this procedure. We examined factors that may influence blastocyst development when ICSI is performed clinically, i.e., on oocytes recovered from live mares by transvaginal ultrasound-guided follicle aspiration (TVA), using sperm from the stallion of the client's choice. In a clinical setting, there may be a delay from the time of TVA to isolation of oocytes from the aspirated fluid. In a preliminary study, oocytes from fluid held for 1.5 h at ambient temperature (26°C-33°C) yielded 32% blastocysts; however, in experiment 1, fluid held at 32 °C for 2 h after aspiration yielded 16% blastocysts versus 23% for aspirates processed immediately. Performing TVA/ICSI throughout the year would increase production from valuable mares, but efficiency during the nonbreeding season is unknown. In addition, to reduce the possibility of infection after TVA, administration of antibiotics to the mare before TVA is indicated; however, these could affect oocyte quality. In experiment 2, follicle numbers at the time of TVA were significantly higher in December to January than for the same mares during the breeding season. Oocyte recovery rates on TVA were 60% to 66% and the blastocyst rate was 18%. An equivalent blastocyst rate (18%) was achieved after administration of ampicillin and gentamicin to mares before TVA. In experiment 3, we verified that stallion differences exist in rates of cleavage after ICSI with motile sperm. In sperm from a low-performing stallion, density-gradient centrifugation followed by swim-up was associated with significantly higher rates of cleavage (45% vs. 18%) and blastocyst development (14% vs. 0%) than those for density gradient alone. In experiment 4, parthenogenetic activation with ionomycin and 6-dimethylaminopurine yielded 40% blastocysts. Frozen-thawed sperm that were immotile after nitrogen tank failure did not produce blastocysts; exogenous activation after ICSI increased cleavage rate but did not yield blastocysts. These studies provide information on factors that may affect in vitro blastocyst formation after equine ICSI as it is performed in a clinical program.
Assuntos
Blastocisto/fisiologia , Técnicas de Cultura Embrionária/veterinária , Cavalos/embriologia , Injeções de Esperma Intracitoplásmicas/veterinária , Animais , Feminino , Técnicas de Maturação in Vitro de Oócitos/veterinária , Masculino , Espermatozoides/fisiologiaRESUMO
In recent years, the rise of human fungal infections has been associated to lack of early diagnosis, uneffective antifungal therapies and vaccines. Disturbance in immune homeostasis, which can be caused by medical interventions and immunosuppression nduced by disease, are well known as risk factors for these pathologies. Cells of the innate immune system are equipped with surface and cytoplasmic receptors for recognition of microorganisms called pattern recognition receptors (PRRs). PRRs recognize specific pathogen-associated molecular patterns (PAMPs) that are crucial for the activation and killing of pathogenic fungi by immune system. This review will outline the PRRs and cells required for effective antifungal immunity, with a special focus on the major antifungal cytokine IL-17. Finally, naturally occurring human mutations involved in the increased susceptibility to fungal infections are also discussed.