The role of glycated hemoglobin in the diagnosis of prediabetes and diabetes mellitus in young women with polycystic ovary syndrome.

OBJECTIVE: To compare glycated hemoglobin (HbA1c) and the oral glucose tolerance test (OGTT) for the diagnosis of prediabetes and diabetes in young women with polycystic ovary syndrome (PCOS). PATIENTS AND DESIGN: This cross-sectional study included 154 women aged 20-40 years with a diagnosis of PCOS, who were screened for prediabetes and diabetes by the OGTT and HbA1c. Women with diabetes, hyperprolactinemia, thyroid or adrenal diseases, and anemia and users of hormonal contraception or corticosteroids were excluded. MEASUREMENTS: Clinical, biochemical and ultrasound data were collected from the electronic medical records. The women were classified as having normal glucose metabolism, prediabetes, or diabetes based on the diagnostic tests. Sensitivity and specificity were calculated and the Kappa method was used to assess agreement between the two methods. RESULTS: According to the OGTT and HbA1c values, 79.2% and 76% of the women were within the normal range, respectively, 16.8% and 19.5% had prediabetes, and 4% and 4.5% had diabetes (p > .05). The Kappa coefficient of 0.41 (95% confidence interval: 0.24-0.58) indicated medium agreement between methods. Considering the OGTT as the gold standard, the specificity of HbA1c was 89.5% and sensitivity was 85.7% in the diagnosis of prediabetes and 100% and 66.7%, respectively, in the diagnosis of diabetes. CONCLUSION: The HbA1c, when compared to the OGTT, showed high sensitivity and specificity in the diagnosis of prediabetes in young women with PCOS.

Proteomic analysis of Trypanosoma cruzi spliceosome complex.

The unicellular protists of the group Kinetoplastida include the genera Leishmania and Trypanosoma, which are pathogens of invertebrate and vertebrate animals. Despite their medical and economical importance, critical aspects of their biology such as specific molecular characteristics of gene expression regulation are just beginning to be deciphered. Gene expression regulation also depends on post-transcriptional processing steps, such as the trans-splicing process. Despite being widely used in trypanosomes, trans-splicing is a rare event in other eukaryotes. We sought to describe the protein composition of spliceosomes in epimastigotes of T. cruzi, the etiological agent of Chagas disease. We used two TAP-tagged proteins to affinity purify spliceosomes and analyzed their composition by mass spectrometry. Among the 115 identified proteins we detected conserved spliceosome components, as Sm and LSm proteins, RNA helicases, U2- and U5-snRNP specific proteins. Importantly, by comparing our data with proteomic data of human and T. brucei spliceosome complexes, we observed a core group of proteins common to all spliceosomes. By using amino acid sequence comparisons, we identified RNA-associated proteins that might be involved with splicing regulation in T. cruzi, namely the orthologous of WDR33, PABPCL1 and three different HNRNPs. Data are available via ProteomeXchange with identifier PXD018776.

The Influence of Environmental Cues on the Development of Trypanosoma cruzi in Triatominae Vector.

Trypanosoma cruzi, a hemoflagellate parasite, is the etiological agent of Chagas disease that affects about 6-7 million people worldwide, mostly in Latin America. The parasite life cycle is complex and alternates between an invertebrate host-Triatominae vector-and a mammalian host. The parasite adaptation to the several microenvironments through which it transits is critical to success in establishing infection. Moreover, environmental cues also play an important role on the parasite development, and it can modulate the infection. In the present study, we discussed how the temperature oscillations and the nutritional state of the invertebrate host can affect the parasite development, multiplication, and the differentiation process of epimastigote forms into metacyclic trypomastigotes, called metacyclogenesis. The impact of oxidative imbalance and osmotic stresses on the parasite-vector relationship are also discussed.

Response to anti-PD1 immunotherapy in patients with metastatic cutaneous sarcoma: case reports and literature review.

Dermal sarcomas represent a group or rare malignancies of mesenchymal origin. Although surgical excision with wide margins can be curative, in the advanced/metastatic setting, treatment options are limited and the benefit from anthracycline-based chemotherapy or targeted agents is usually short-lived. Tumor mutational burden and PD-L1 expression scores can be used as predictive biomarker for response to immunotherapy in some metastatic cancers. The role of immune-checkpoint blockade for sarcoma patients remains investigational. Here we present three cases of dermal sarcomas with high TMB and PD-L1 expression and responses to anti-PD1 agents in two of them.

Structure of Urocanate Hydratase from the protozoan Trypanosoma cruzi.

The enzyme Urocanate Hydratase (UH) participates in the catabolic pathway of L-histidine. Trypanosoma cruzi Urocanate Hydratase (TcUH) is identified as a therapeutic molecular target in the WHO/TDR Targets Database. We report the 3D structure determination and number of features of TcUH, and compared it to other few available bacterial UH structures. Each monomer presents two domains and one NAD+ molecule. Superpositions revealed differences in the relative orientation of domains within monomers, such that TcUH monomer A resembles Urocanate Hydratase from Geobacillus kaustophilus (GkUH) (open conformation), while monomer C resembles Urocanate Hydratase from Pseudomonas putida (PpUH) and Urocanate Hydratase from Bacillus subtilis (BsUH) (closed conformations). We use the structure of TcUH to make considerations about 3 non-deleterious and 2 deleterious mutations found in human UHs: non-deleterious mutations could be accommodated without large displacements or interaction interruptions, whereas deleterious mutations in one case might disrupt an α-helix (as previously suggested) and in the other case, besides disrupting the enzyme interaction with the substrate, might interfere with interdomain movement.

Proteomic analysis of Trypanosoma cruzi spliceosome complex

The unicellular protists of the group Kinetoplastida include the genera Leishmania and Trypanosoma, which are pathogens of invertebrate and vertebrate animals. Despite their medical and economical importance, critical aspects of their biology such as specific molecular characteristics of gene expression regulation are just beginning to be deciphered. Gene expression regulation also depends on post-transcriptional processing steps, such as the trans-splicing process. Despite being widely used in trypanosomes, trans-splicing is a rare event in other eukaryotes. We sought to describe the protein composition of spliceosomes in epimastigotes of T. cruzi, the etiological agent of Chagas disease. We used two TAP-tagged proteins to affinity purify spliceosomes and analyzed their composition by mass spectrometry. Among the 115 identified proteins we detected conserved spliceosome components, as Sm and LSm proteins, RNA helicases, U2- and U5-snRNP specific proteins. Importantly, by comparing our data with proteomic data of human and T. brucei spliceosome complexes, we observed a core group of proteins common to all spliceosomes. By using amino acid sequence comparisons, we identified RNA-associated proteins that might be involved with splicing regulation in T. cruzi, namely the orthologous of WDR33, PABPCL1 and three different HNRNPs. Data are available via ProteomeXchange with identifier PXD018776.