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1.
Mol Microbiol ; 119(5): 574-585, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36855815

RESUMO

The CUG-Ser1 clade-specific histone H3 variant (H3VCTG ) has been reported to be a negative regulator of planktonic to biofilm growth transition in Candida albicans. The preferential binding of H3VCTG at the biofilm gene promoters makes chromatin repressive for the biofilm mode of growth. The two evolutionarily conserved chaperone complexes involved in incorporating histone H3 are CAF-1 and HIRA. In this study, we sought to identify the chaperone complex(es) involved in loading H3VCTG . We demonstrate that C. albicans cells lacking either Cac1 or Cac2 subunit of the CAF-1 chaperone complex, exhibit a hyper-filamentation phenotype on solid surfaces and form more robust biofilms than wild-type cells, thereby mimicking the phenotype of the H3VCTG null mutant. None of the subunits of the HIRA chaperone complex shows any significant difference in biofilm growth as compared to the wild type. The occupancy of H3VCTG is found to be significantly reduced at the promoters of biofilm genes in the absence of CAF-1 subunits. Hence, we provide evidence that CAF-1, a chaperone known to load canonical histone H3 in mammalian cells, is involved in chaperoning of variant histone H3VCTG at the biofilm gene promoters in C. albicans. Our findings also illustrate the acquisition of an unconventional role of the CAF-1 chaperone complex in morphogenesis in C. albicans.


Assuntos
Candida albicans , Histonas , Animais , Histonas/genética , Histonas/metabolismo , Candida albicans/genética , Candida albicans/metabolismo , Chaperonas de Histonas/genética , Chaperonas de Histonas/metabolismo , Cromatina , Fator 1 de Modelagem da Cromatina/química , Fator 1 de Modelagem da Cromatina/genética , Fator 1 de Modelagem da Cromatina/metabolismo , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Biofilmes , Mamíferos/genética , Mamíferos/metabolismo
2.
Ann Diagn Pathol ; 71: 152300, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38574567

RESUMO

INTRODUCTION: Fine Needle Aspiration cytology (FNAC) and core needle biopsy (CNB) are rapid, minimally invasive and useful techniques to evaluate mediastinal lesions. OBJECTIVES: To compare cytopathology with histopathology of mediastinal lesions and analyse reasons for discordance. MATERIAL & METHODS: Retrospective analysis was done in a tertiary care centre in North West India over a period of seven and half years from 1stJuly 2016 to 31st December 2023. Only those patients who had undergone FNAC and trucut biopsy of mediastinal masses were included. The cytopathology and histopathology slides were studied to analyse causes of discordance. Sensitivity, specificity, positive and negative predictive values of FNAC were calculated keeping histopathology as gold standard. RESULTS: Out of 57 cases analysed, eight cases were non diagnostic on cytology. Cytology could effectively classify a lesion as non neoplastic (7) or neoplastic (42). For further subtyping, histopathology and Immunohistochemistry (IHC) were required. Out of 27 cases of cytological - histopathological discordance, 8 cases had sampling error, 15 cases had limited concordance where FNAC could predict possibility of tumor and 4 cases were discordant where subtyping of malignancy varied on CNB. Sensitivity of FNAC to predict definite diagnosis was 90.2 %, specificity was 50 %, positive predictive value of FNAC to give a definite diagnosis was 93.9 %, negative predictive value was 37.5 %. CONCLUSION: Evaluation of mediastinal masses requires combination of cytology, histopathology and ancillary techniques like IHC. FNAC and CNB are complementary modalities and both are essential for rapid, accurate and comprehensive diagnosis.


Assuntos
Neoplasias do Mediastino , Mediastino , Sensibilidade e Especificidade , Humanos , Biópsia com Agulha de Grande Calibre/métodos , Estudos Retrospectivos , Biópsia por Agulha Fina/métodos , Masculino , Feminino , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/diagnóstico , Adulto , Pessoa de Meia-Idade , Mediastino/patologia , Índia , Idoso , Adulto Jovem , Adolescente , Citodiagnóstico/métodos , Valor Preditivo dos Testes , Criança , Citologia
3.
Acad Psychiatry ; 46(4): 421-427, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34292538

RESUMO

OBJECTIVE: The USA needs to produce more psychiatrists to meet projected workforce deficits. The American Association of Directors of Psychiatric Residency Training Directors (AADPRT) sought to examine opportunities for and obstacles to expanding or creating residencies and fellowships. METHODS: In November 2019, the authors conducted a survey of residency and fellowship directors. The survey gathered information about new positions, new programs, participation in interprofessional education, and loss of residency or fellowship positions. RESULTS: The survey was distributed to psychiatry residency (N=231) and fellowship (N=194) directors, with a response rate of 33.4%. One quarter of responding residencies and fellowships reported creating new programs; 24.7% of residency and 17.5% of fellowships reported expansion. The most common reason to develop or expand programs was the shortage of psychiatrists, with the local institution as the most common funding source. Fifty-seven percent reported that they had wanted to expand, but faced barriers, primarily lack of funding. Recruitment and retention of faculty are major challenges. Psychiatry departments frequently (87.5%) participate in interprofessional education, generally perceived as positive. Unfortunately, 15.7% of respondents reported loss of positions or closure of programs. CONCLUSIONS: Creating and expanding residencies and fellowships are common strategies for addressing the shortage of psychiatrists. Barriers include lack of funding and challenges recruiting/retaining faculty. The loss of residency/fellowship positions or closure of programs is a worrisome trend.


Assuntos
Internato e Residência , Psiquiatria , Educação de Pós-Graduação em Medicina , Bolsas de Estudo , Humanos , Inquéritos e Questionários , Estados Unidos , Recursos Humanos
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