Topical Application of Imiquimod as a Treatment for Chromoblastomycosis

Peer reviewedPublisher PD

Human eyes do not need monochromatic aberrations for dynamic accommodation.

PURPOSE: To determine if human accommodation uses the eye's own monochromatic aberrations to track dynamic accommodative stimuli. METHODS: Wavefront aberrations were measured while subjects monocularly viewed a monochromatic Maltese cross moving sinusoidally around 2D of accommodative demand with 1D amplitude at 0.2 Hz. The amplitude and phase (delay) of the accommodation response were compared to the actual vergence of the stimulus to obtain gain and temporal phase, calculated from wavefront aberrations recorded over time during experimental trials. The tested conditions were as follows: Correction of all the subject's aberrations except defocus (C); Correction of all the subject's aberrations except defocus and habitual second-order astigmatism (AS); Correction of all the subject's aberrations except defocus and odd higher-order aberrations (HOAs); Correction of all the subject's aberrations except defocus and even HOAs (E); Natural aberrations of the subject's eye, i.e., the adaptive-optics system only corrected the optical system's aberrations (N); Correction of all the subject's aberrations except defocus and fourth-order spherical aberration (SA). The correction was performed at 20 Hz and each condition was repeated six times in randomised order. RESULTS: Average gain (±2 standard errors of the mean) varied little across conditions; between 0.55 ± 0.06 (SA), and 0.62 ± 0.06 (AS). Average phase (±2 standard errors of the mean) also varied little; between 0.41 ± 0.02 s (E), and 0.47 ± 0.02 s (O). After Bonferroni correction, no statistically significant differences in gain or phase were found in the presence of specific monochromatic aberrations or in their absence. CONCLUSIONS: These results show that the eye's monochromatic aberrations are not necessary for accommodation to track dynamic accommodative stimuli

Sistemas de seguro nacional de saúde e respostas às legitimas expectativas dos cidadãos

Os sistemas de saúde assumem a responsabilidade não só de melhorar a saúde das populações mas também de as proteger do custo da doença e de as tratar com dignidade. Tendo por base as três dimensões que definem os sistemas de saúde (regulação, financiamento e prestação), e que cada dimensão pode ser dominada por três tipos de atores (estado, social e privado), no âmbito deste trabalho é nosso propósito estudar os sistemas de saúde de tipo Seguro Nacional de Saúde (nomeadamente dos países como o Canadá, a Austrália, a Nova Zelândia e a Irlanda), na perspetiva das respostas às legitimas expectativas dos cidadãos. Assim, iremos proceder a uma revisão da literatura para chegarmos aos objetivos específicos: (i) descrever sucintamente os sistemas de saúde baseados no seguro nacional de saúde, onde se podem incluir a Austrália, Canadá, Irlanda e Nova Zelândia; (ii) caracterizar o conceito de responsiveness; (iii) identificar a presença da responsiveness nestes sistemas. A forma como os sistemas de saúde interagem com as pessoas é determinante para o seu bem estar. Avaliar o desempenho dos sistemas de saúde não se limita à avaliação dos resultados em saúde mas também no respeito e integração dos princípios éticos e dos direitos humanos

Investigation of latent tuberculosis infection in patients with psoriasis who are candidate for receiving immunobiological drugs

O uso dos inibidores do fator de necrose tumoral no tratamento de pacientes com psoríase vem sendo relacionado a uma maior incidência de tuberculose, particularmente, nas suas formas extrapulmonar e disseminada. Apesar de sua indiscutível eficácia, essas drogas elevam o risco da reativação de infecção tuberculosa latente (ITBL), tornando obrigatório o diagnóstico da referida condição antes da sua administração. A investigação da infecção tuberculosa latente pelo teste cutâneo da tuberculina é falha, dada sua baixa especificidade, além de apresentar resultados duvidosos em pacientes com psoríase. Ensaios baseados na detecção da produção de interferon-gama in vitro por células monoclonais periféricas, estimuladas por antígenos específicos (Esat-6 e CFP-10), parecem oferecer maior acurácia quando comparados ao teste de Mantoux na identificação de infecção tuberculosa latente. Essa ferramenta diagnóstica tem oferecido maior especificidade, já que não apresenta correlação com medidas indiretas de exposição ao M. tuberculosis, como a vacinação por BCG, e com infecções por outras micobactériasThe use of tumor necrosis factor inhibitors for the treatment of patients with psoriasis has been related to a higher incidence of tuberculosis, specially the disseminated and extrapulmonary forms. Despite their efficacy, these drugs increase the risk of reactivating latent tuberculosis infection, thus requiring diagnosis of the condition before their administration. Investigation of latent tuberculosis infection with tuberculin skin test is ineffective due to its low specificity and the dubious results that it generates in patients with psoriasis. Assays based on the detection of synthesis of gamma interferon in vitro by peripheral monoclonal cells, stimulated by specific antigens (ESAT-6 and CFP-10), seem to offer better accuracy when compared to the Mantoux test in identifying latent tuberculosis infection. This diagnosis tool has demonstrated higher specificity, since it has no correlation with indirect forms of exposure to M. tuberculosis such as BCG vaccination or with infections by other mycobacteri

Impact of Cytomegalovirus and Grafts versus Host Disease on the Dynamics of CD57+CD28−CD8+ T Cells After Bone Marrow Transplant

OBJECTIVES: The present study aimed to evaluate the dynamics of CD28 and CD57 expression in CD8+ T lymphocytes during cytomegalovirus viremia in bone marrow transplant recipients. METHODS: In a prospective study, blood samples were obtained once weekly once from 33 healthy volunteers and weekly from 33 patients. To evaluate the expression of CD57 and CD28 on CD8+ T lymphocytes, flow cytometry analysis was performed on blood samples for four months after bone marrow transplant, together with cytomegalovirus antigenemia assays. RESULTS: Compared to cytomegalovirus-seronegative healthy subjects, seropositive healthy subjects demonstrated a higher percentage of CD57+ and a lower percentage of CD28+ cells (p<0.05). A linear regression model demonstrated a continuous decrease in CD28+ expression and a continuous increase in CD57+ expression after bone marrow transplant. The occurrence of cytomegalovirus antigenemia was associated with a steep drop in the percentage of CD28+ cells (5.94%, p<0.01) and an increase in CD57+ lymphocytes (5.60%, p<0.01). This cytomegalovirus-dependent effect was for the most part concentrated in the allogeneic bone marrow transplant patients. The development of acute graft versus host disease, which occurred at an earlier time than antigenemia (day 26 vs. day 56 post- bone marrow transplant), also had an impact on the CD57+ subset, triggering an increase of 4.9% in CD57+ lymphocytes (p<0.05). CONCLUSION: We found continuous relative changes in the CD28+ and CD57+ subsets during the first 120 days post- bone marrow transplant, as part of immune system reconstitution and maturation. A clear correlation was observed between the expansion of the CD57+CD28-CD8+ T lymphocyte subpopulation and the occurrence of graft versus host disease and cytomegalovirus viremia

Fatal septic shock due to a disseminated chronic form of paracoccidioidomycosis in an aged woman

Once rare, septic shock (SS) due to disseminated fungal infections has been increasingly reported due to a growing number of immunocompromised patients, but remains rare in non-immune-compromised individuals. In paracoccidioidomycosis, it has been described in only three patients with the severe, acute form of the disease. We describe the development of a refractory, fatal septic shock due to a severe disseminated chronic form of paracoccidioidomycosis in an older woman without any other microbial insults. A striking event in the evolution of her case was the severe depletion of lymphocytes from the peripheral blood and lymphoid organs. Lymphocyte depletion due to apoptosis is described in the late phase of sepsis and can contribute both to immunosuppression and the progression of SS. The possible mechanisms involved in the induction of SS in the chronic form of paracoccidioidomycosis are discussed

Can COVID-19 impact the natural history of paracoccidioidomycosis? Insights from an atypical chronic form of the mycosis

Paracoccidioidomycosis (PCM) is a systemic fungal infection caused by Paracoccidioides spp. It can occur as an acute/subacute form (A/SAF), a chronic form (CF) and rarely as a mixed form combining the features of the two aforementioned forms in an immunocompromised patient. Here, we report a 56-year-old male patient with CF-PCM who presented with atypical manifestations, including the development of an initial esophageal ulcer, followed by central nervous system (CNS) lesions and cervical and abdominal lymphatic involvement concomitant with severe SARS-CoV-2 infection. He was HIV-negative and had no other signs of previous immunodeficiency. Biopsy of the ulcer confirmed its mycotic etiology. He was hospitalized for treatment of COVID-19 and required supplemental oxygen in the intensive unit. The patient recovered without the need for invasive ventilatory support. Investigation of the extent of disease during hospitalization revealed severe lymphatic involvement typical of A/SAF, although the patient`s long history of high-risk exposure to PCM, and lung involvement typical of the CF. Esophageal involvement is rare in non-immunosuppressed PCM patients. CNS involvement is also rare. We suggest that the immunological imbalance caused by the severe COVID-19 infection may have contributed to the patient developing atypical severe CF, which resembles the PCM mixed form of immunosuppressed patients. Severe COVID-19 infection is known to impair the cell-mediated immune response, including the antiviral response, through T-lymphopenia, decreased NK cell counts and T-cell exhaustion. We hypothesize that these alterations would also impair antifungal defenses. Our case highlights the potential influence of COVID-19 on the course of PCM. Fortunately, the patient was timely treated for both diseases, evolving favorably

In situ immune response in human dermatophytosis: possible role of Langerhans cells (CD1a+) as a risk factor for dermatophyte infection

Dermatophytosis is a cutaneous mycosis caused by a plethora of keratinophilic fungi, but Trichophyton rubrum is the most common etiological agent. Despite its high prevalence worldwide, little is known about the host defense mechanisms in this infection, particularly the in situ immune response. Using an immunohistochemistry approach, we investigated the density of CD1a+, factor XIIIa+ and CD68+ cells in the skin of dermatophytosis patients. Langerhans cells (CD1a+ cells) were significantly decreased in the epidermis of patients, both in affected and unaffected areas. In the dermis, however, no differences in the density of macrophages (CD68+ cells) and dermal dendrocytes (factor XIIIa+ cells) were observed. These results suggest that the decreased number of Langerhans cells may be a risk factor for development of dermatophytosis

Retirada da terapia de manutenção para retinite por citomegalovírus em pacientes com aids exibindo resposta imunológica à terapia anti-retroviral altamente efetiva (HAART)

BACKGROUND: Before the introduction of highly active antiretroviral therapy (HAART), CMV retinitis was a common complication in patients with advanced HIV disease and the therapy was well established; it consisted of an induction phase to control the infection with ganciclovir, followed by a lifelong maintenance phase to avoid or delay relapses. METHODS: To determine the safety of CMV maintenance therapy withdrawal in patients with immune recovery after HAART, 35 patients with treated CMV retinitis, on maintenance therapy, with CD4+ cell count greater than 100 cells/mm³ for at least three months, but almost all patients presented these values for more than six months and viral load < 30000 copies/mL, were prospectively evaluated for the recurrence of CMV disease. Maintenance therapy was withdrawal at inclusion, and patients were monitored for at least 48 weeks by clinical and ophthalmologic evaluations, and by determination of CMV viremia markers (antigenemia-pp65), CD4+/CD8+ counts and plasma HIV RNA levels. Lymphoproliferative assays were performed on 26/35 patients. RESULTS: From 35 patients included, only one had confirmed reactivation of CMV retinitis, at day 120 of follow-up. No patient returned positive antigenemia tests. No correlation between lymphoproliferative assays and CD4+ counts was observed. CONCLUSION: CMV retinitis maintenance therapy discontinuation is safe for those patients with quantitative immune recovery after HAART.Antes da introdução da terapia anti-retroviral altamente efetiva (HAART), a retinite por CMV era uma complicação comum em pacientes com doença por HIV avançada e a terapia era bem estabelecida e consistia em uma fase de indução com ganciclovir para controlar a infecção, seguida por uma manutenção por toda a vida, para evitar e retardar as recidivas. Para determinar a segurança da retirada da terapia de manutenção para retinite por citomegalovírus em pacientes com recuperação imunológica após o HAART, 35 pacientes com retinite por CMV tratados com terapia de manutenção, com contagem de células CD4+ maiores que 100 células/mm³ por no mínimo três meses, mas a maioria dos pacientes apresentava esses valores por mais de seis meses e carga viral < 30.000 cópias/mL, foram avaliados prospectivamente para a recorrência de doença por CMV. A terapia de manutenção foi retirada na inclusão e os pacientes foram monitorados no mínimo 48 semanas por avaliações clínicas e oftalmológicas e pela determinação de marcadores de viremia para CMV (antigenemia). Contagens de CD4+ e CD8+ e níveis de RNA de HIV no plasma. Métodos linfoproliferativos foram realizados em 26/35 pacientes. RESULTADOS: Dos 35 pacientes incluídos no estudo, somente um teve reativação da retinite por CMV confirmada, no dia 120 do seguimento. Nenhum paciente teve testes de antigenemia positivos. Nenhuma correlação entre os ensaios linfoproliferativos e contagens de CD4+ foi observada. CONCLUSÃO: Descontinuação da terapia de manutenção para retinite por CMV é segura para aqueles pacientes com recuperação imune quantitativa após HAART

Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for Differentiation of the Dimorphic Fungal Species Paracoccidioides brasiliensis and Paracoccidioides lutzii

Isolates of Paracoccidioides brasiliensis and Paracoccidioides lutzii, previously characterized by molecular techniques, were identified for the first time by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). All isolates were correctly identified, with log score values of >2.0. Thus, MALDI-TOF MS is a new tool for differentiating species of the genus Paracoccidioides.Univ São Paulo, Fac Med, Hosp Clin, Cent Lab Div LIM03, São Paulo, BrazilUniv São Paulo, Inst Med Trop, Hosp Clin FMUSP, Lab Med Mycol LIM53, São Paulo, BrazilUniv São Paulo, Dept Biophys, Escola Paulista Med, São Paulo, BrazilUniv Estadual Paulista, Dept Microbiol & Immunol, Inst Biociencias Botucatu, Botucatu, SP, BrazilUniv São Paulo, Dept Biophys, Escola Paulista Med, São Paulo, BrazilWeb of Scienc