Allelic variation in class I HLA determines CD8+ T cell repertoire shape and cross-reactive memory responses to SARS-CoV-2.

Effective presentation of antigens by human leukocyte antigen (HLA) class I molecules to CD8+ T cells is required for viral elimination and generation of long-term immunological memory. In this study, we applied a single-cell, multiomic technology to generate a unified ex vivo characterization of the CD8+ T cell response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across four major HLA class I alleles. We found that HLA genotype conditions key features of epitope specificity, TCRα/ß sequence diversity, and the utilization of pre-existing SARS-CoV-2-reactive memory T cell pools. Single-cell transcriptomics revealed functionally diverse T cell phenotypes of SARS-CoV-2-reactive T cells, associated with both disease stage and epitope specificity. Our results show that HLA variations notably influence the CD8+ T cell repertoire shape and utilization of immune recall upon SARS-CoV-2 infection.

Cancer Cell Discrimination Using Host-Guest "Doubled" Arrays.

We report a nanosensor that uses cell lysates to rapidly profile the tumorigenicity of cancer cells. This sensing platform uses host-guest interactions between cucurbit[7]uril and the cationic headgroup of a gold nanoparticle to non-covalently modify the binding of three fluorescent proteins of a multi-channel sensor in situ. This approach doubles the number of output channels to six, providing single-well identification of cell lysates with 100% accuracy. Significantly, this classification could be extended beyond the training set, determining the invasiveness of novel cell lines. The unique fingerprint of these cell lysates required minimal sample quantity (200 ng, ∼1000 cells), making the methodology compatible with microbiopsy technology.

Historical trends in the epidemiology of candidaemia: analysis of an 11-year period in a tertiary care hospital in Brazil.

Candida species are an important cause of bloodstream infections (BSI). To evaluate the epidemiological, clinical and microbiological aspects of two cohorts {1994-1999 [period 1 (P1) ]; 2000-2004 [period 2 (P2) ]} of candidaemic patients, we performed a retrospective analysis from a laboratory-based survey. A total of 388 candidaemias were identified, with an incidence of 0.20/1,000 patient-days and a significant increase in P2 vs. P1 (0.25 vs. 0.15, p = 0.04). Cancer and prior antibiotic use were frequent and Candida albicans was the most prevalent species found (42.4%). Resistance to fluconazole was found in 2.47% of the strains. No differences were observed in the species distribution of Candida during the study periods. In the P2 cohort, there were higher prevalence of elderly individuals, cardiac, pulmonary and liver diseases, renal failure, central venous catheters and antibiotic therapy. In P1, there were higher prevalence of neurological diseases and chemotherapy. The crude mortality was 55.4%. In conclusion, our incidence rates remained high. Furthermore, the distribution pattern of Candida species and the fluconazole resistance profile remained unchanged. Moreover, we found a clear trend of higher prevalence of candidaemia among the elderly and among patients with comorbidities. Finally, it is necessary to discuss strategies for the prevention and control of Candida BSI in Brazil.

Historical trends in the epidemiology of candidaemia: analysis of an 11-year period in a tertiary care hospital in Brazil

Candida species are an important cause of bloodstream infections (BSI). To evaluate the epidemiological, clinical and microbiological aspects of two cohorts {1994-1999 [period 1 (P1) ]; 2000-2004 [period 2 (P2) ]} of candidaemic patients, we performed a retrospective analysis from a laboratory-based survey. A total of 388 candidaemias were identified, with an incidence of 0.20/1,000 patient-days and a significant increase in P2 vs. P1 (0.25 vs. 0.15, p = 0.04). Cancer and prior antibiotic use were frequent and Candida albicans was the most prevalent species found (42.4%). Resistance to fluconazole was found in 2.47% of the strains. No differences were observed in the species distribution of Candida during the study periods. In the P2 cohort, there were higher prevalence of elderly individuals, cardiac, pulmonary and liver diseases, renal failure, central venous catheters and antibiotic therapy. In P1, there were higher prevalence of neurological diseases and chemotherapy. The crude mortality was 55.4%. In conclusion, our incidence rates remained high. Furthermore, the distribution pattern of Candida species and the fluconazole resistance profile remained unchanged. Moreover, we found a clear trend of higher prevalence of candidaemia among the elderly and among patients with comorbidities. Finally, it is necessary to discuss strategies for the prevention and control of Candida BSI in Brazil.

Pharmacokinetics and pharmacodynamics of antimicrobial drugs in intensive care unit patients.

Inappropriate use of antimicrobial drugs is responsible for therapeutic failures, increased mortality rates, and the emergence of resistance. Antimicrobial activity is determined by intrinsic pharmacokinetics/pharmacodynamics concepts. In critically ill patients, an inappropriate dosing regimen can be caused by the inability of an antimicrobial drug to reach adequate concentrations at the infection site owing to alterations in the drug's pharmacokinetics caused by pathophysiological changes. Understanding these concepts and changes in PK-PD parameters that occur in intensive care unit patients is crucial for the optimization of antimicrobial therapy in these patients.

Epidemiologia das dermatomicoses em população da periferia de Araraquara - SP / Epidemiology of dermatomycoses in population in the outskirts of Araraquara - SP

JUSTIFICATIVA E OBJETIVOS: Dermatomicoses são doenças fúngicas que acometem a pele, unhas e cabelos de homens e animais, sendo altamente prevalentes na América Latina. O objetivo deste estudo foi identificar lesões características de micoses em frequentadores de Albergues e na população da periferia da cidade de Araraquara, SP. MÉTODO: Os voluntários que participaram da pesquisa foram atendidos na Casa Transitória e nas Unidades Básicas de Saúde (UBS) do município de Araraquara – SP no ano de 2007. Foi realizada uma triagem de dermatomicoses, aquelas lesões que apresentavam características semelhantes foram submetidas à coleta, através de raspado de pele, unha, cabelo, sendo as amostras biológicas armazenadas em placas estéreis para o posterior processamento do material micológico. Após exame direto e cultura desses materiais, foram identificados os principais fungos responsáveis pelas lesões. RESULTADOS: Das 93 amostras coletadas, 40 (43%) foram positivas somente em cultura (sendo que 22 (23,6%) para dermatofitose, 15 (16,2%) para leveduras do gênero Candida e 3 (3,2%) para agentes de micoses superficiais), 15 (16,2%) amostras positivas para fungos, no exame direto não foi possível isolamento em cultura e 38 (40,8%) amostras negativas. O resultado mostrou que os pés foram as áreas anatômicas mais acometidas, a faixa etária entre 41e 50 anos foi a mais atingida e ambos os sexos apresentaram o mesmo número de casos de dermatomicose. CONCLUSÃO: Esse estudo permitiu conhecer a epidemiologia das dermatomicoses, embora essas desordens não sejam sérias em termos de mortalidade, lesões físicas e/ou psicológicas, elas têm significativa consequência clínica, com lesões crônicas, de difícil tratamento, contagiosas, além de problemas estéticos.