ABSTRACT BACKGROUND: Managing cervical intraepithelial neoplasia grade 2 (CIN2) is challenging, considering the CIN2 regression rate, perinatal risks associated with excisional procedures, and insufficient well-established risk factors to predict progression. OBJECTIVES: To determine the ability of p16INK4a and Ki-67 staining in biopsies diagnosed with CIN2 to identify patients with higher-grade lesions (CIN3 or carcinoma). DESIGN AND SETTING: Cross-sectional study conducted at a referral center for treating uterine cervical lesions. METHODS: In 79 women, we analyzed the correlation of p16INK4a and Ki-67 expression in CIN2 biopsies with the presence of a higher-grade lesions, as determined via histopathology in surgical specimens from treated women or via two colposcopies and two cytological tests during follow-up for untreated women with at least a 6-month interval. The expression of these two biomarkers was verified by at least two independent pathologists and quantified using digital algorithms. RESULTS: Thirteen (16.8%) women with CIN2 biopsy exhibited higher-grade lesions on the surgical excision specimen or during follow-up. p16INK4a expression positively and negatively predicted the presence of higher-grade lesions in 17.19% and 86.67% patients, respectively. Ki-67 expression positively and negatively predicted the presence of higher-grade lesions in 40% and 88.24% patients, respectively. CONCLUSIONS: Negative p16INK4a and Ki67 immunohistochemical staining can assure absence of a higher-grade lesion in more than 85% of patients with CIN2 biopsies and can be used to prevent overtreatment of these patients. Positive IHC staining for p16INK4a and Ki-67 did not predict CIN3 in patients with CIN2 biopsies. BACKGROUND CIN (CIN2 challenging rate procedures wellestablished well established progression OBJECTIVES pINKa p INK Ki 67 Ki-6 highergrade higher (CIN carcinoma. carcinoma . carcinoma) SETTING Crosssectional Cross sectional METHODS 7 followup follow up 6month month 6 interval algorithms RESULTS 16.8% 168 16 8 (16.8% followup. up. 1719 17 19 17.19 8667 86 86.67 respectively 40 8824 88 24 88.24 CONCLUSIONS Ki6 85 Ki- 16.8 1 (16.8 171 17.1 866 86.6 4 882 88.2 16. (16. 17. 86. 88. (16 (1 (

Abstract Background The p53 and p21 proteins are important regulators of cell cycle and apoptosis and may contribute to autoimmune diseases, such as systemic lupus erythematosus (SLE). As genetic polymorphisms may cause changes in protein levels and functions, we investigated associations of TP53 and p21 (CDKN1A) polymorphisms (p53 72 G > C—rs1042522; p53 PIN3—rs17878362; p21 31 C > A—rs1801270; p21 70 C > T—rs1059234) with the development of systemic lupus erythematosus (SLE) in a Southeastern Brazilian population. Methods Genotyping of 353 female volunteers (cases, n = 145; controls, n = 208) was performed by polymerase chain reaction, restriction fragment length polymorphism and/or DNA sequencing. Associations between TP53 and p21 polymorphisms and SLE susceptibility and clinical manifestations of SLE patients were assessed by logistic regression analysis. Results Protective effect was observed for the genotype combinations p53 PIN3 A1/A1 -p21 31 C/A, in the total study population (OR 0.45), and p53 PIN3 A1/A2-p21 31 C/C, in non-white women (OR 0.28). In Whites, p53 72 C-containing (OR 3.06) and p53 PIN3 A2-containing (OR 6.93) genotypes were associated with SLE risk, and higher OR value was observed for the combined genotype p53 72 G/C-p53 PIN3 A1/A2 (OR 9.00). Further, p53 PIN3 A1/A2 genotype was associated with serositis (OR 2.82), while p53 PIN3 A2/A2 and p53 72 C/C genotypes were associated with neurological disorders (OR 4.69 and OR 3.34, respectively). Conclusions Our findings showed that the TP53 and p21 polymorphisms included in this study may have potential to emerge as SLE susceptibility markers for specific groups of patients. Significant interactions of the TP53 polymorphisms with serositis and neurological disorders were also observed in SLE patients. Highlights The polymorphisms TP53 rs1042522 (G > C) and TP53 rs17878362 (16 bp Del/Ins) were associated with SLE risk in whites. In whites, the combined genotype TP53 rs1042522 GC- TP53 rs17878362 A1A2 and the haplotype TP53 rs1042522 C-rs17878362 A2 represented higher SLE risk. Combination of TP53 rs17878362 (16 bp Del/Ins) and p21 rs1801270 (C > A) protected against SLE in non-white women. TP53 and p21 (CDKN1A) polymorphisms may be SLE susceptibility markers for specific groups. p p5 p2 diseases SLE. . functions TP TP5 CDKN1A CDKNA CDKN A (CDKN1A (p5 7 Crs1042522 Crs rs C—rs1042522 PIN3rs17878362 PINrs PIN PIN3—rs17878362 3 Ars1801270 Ars A—rs1801270 Trs1059234 Trs T rs1059234 T—rs1059234 (SLE 35 cases, cases (cases 145 controls 208 reaction andor or sequencing analysis A1A1 AA A1 A1/A -p2 CA C/A 0.45, 045 0.45 , 0 45 0.45) A1/A2p21 A1A2p21 AAp A1/A2-p2 CC nonwhite non white 0.28. 028 0.28 28 0.28) Whites Ccontaining containing 3.06 306 06 A2containing Acontaining 6.93 693 6 93 G/Cp53 GCp53 GCp G/C G/C-p5 9.00. 900 9.00 9 00 9.00) Further 2.82, 282 2.82 2 82 2.82) A2A2 A2/A 469 4 69 4.6 334 34 3.34 respectively. respectively respectively) rs104252 rs1787836 16 (1 Del/Ins DelIns Del Ins whites GC A1A Crs17878362 C-rs1787836 rs180127 (p Crs104252 C—rs104252 PIN3rs1787836 PIN3—rs1787836 Ars180127 A—rs180127 Trs105923 rs105923 T—rs105923 14 20 -p 04 0.4 A2p21 A1/A2p2 A1A2p2 A1/A2-p 02 0.2 3.0 30 6.9 Cp53 Cp G/Cp5 GCp5 G/C-p 90 9.0 2.8 8 A2A 46 4. 33 3.3 rs10425 rs178783 1 ( Crs1787836 C-rs178783 rs18012 Crs10425 C—rs10425 PIN3rs178783 PIN3—rs178783 Ars18012 A—rs18012 Trs10592 rs10592 T—rs10592 0. Ap A2p2 A1/A2p A1A2p 3. 6. Cp5 G/Cp 9. 2. rs1042 rs17878 Crs178783 C-rs17878 rs1801 Crs1042 C—rs1042 PIN3rs17878 PIN3—rs17878 Ars1801 A—rs1801 Trs1059 rs1059 T—rs1059 A2p rs104 rs1787 Crs17878 C-rs1787 rs180 Crs104 C—rs104 PIN3rs1787 PIN3—rs1787 Ars180 A—rs180 Trs105 rs105 T—rs105 rs10 rs178 Crs1787 C-rs178 rs18 Crs10 C—rs10 PIN3rs178 PIN3—rs178 Ars18 A—rs18 Trs10 T—rs10 rs1 rs17 Crs178 C-rs17 Crs1 C—rs1 PIN3rs17 PIN3—rs17 Ars1 A—rs1 Trs1 T—rs1 Crs17 C-rs1 C—rs PIN3rs1 PIN3—rs1 A—rs T—rs C-rs PIN3rs PIN3—rs

SUMMARY OBJECTIVE: The objective of this study was to evaluate the correlation between clinical and serological findings of pregnant women and newborns with patterns of histopathologic changes of the placenta diagnosed with coronavirus disease 2019. METHODS: A prospective descriptive study was conducted with pregnant women who were positive for SARS-CoV-2 by reverse transcription polymerase chain reaction or serology (IgG and IgM). Clinical analyses were performed using ELISA to detect anti-SARS-CoV-2 IgG and IgA antibodies using the S1 spike protein domain with the Euroimmun kit. Histopathologic analyses of placentas were performed by two expert pathologists. RESULTS: Maternal SARS-CoV-2 infection was associated with increased neonatal hospital length of stay (p=0.03), increased preterm birth (p=0.04), and Apgar score<7 at 1st min (p=0.00) and 5th min (p=0.02). Pregnant women with positive IgG and/or IgA at delivery had a higher incidence of placental histopathologic changes in addition to a greater likelihood of having an IgG-positive fetus (p<0.0001). Placentas with positive reverse transcription polymerase chain reaction for SARS-CoV-2 had a higher incidence of histopathologic changes such as maternal vascular hypoperfusion changes (p=0.00). CONCLUSION: Maternal SARS-CoV-2 infection was associated with adverse perinatal outcomes. Pregnant women with positive IgG at delivery had a higher incidence of placental histopathologic changes. Placentas with positive reverse transcription polymerase chain reaction for SARS-CoV-2 had a higher incidence of histopathologic changes such as maternal vascular hypoperfusion. OBJECTIVE 2019 METHODS SARSCoV2 SARSCoV SARS CoV 2 SARS-CoV- IgM. IgM . IgM) antiSARSCoV2 antiSARSCoV anti anti-SARS-CoV- S kit pathologists RESULTS p=0.03, p003 p p=0.03 , 0 03 (p=0.03) p=0.04, p004 p=0.04 04 (p=0.04) score7 score 7 score< st p=0.00 p000 00 (p=0.00 th p=0.02. p002 p=0.02 02 (p=0.02) andor IgGpositive p<0.0001. p00001 p<0.0001 0001 (p<0.0001) p=0.00. CONCLUSION outcomes 201 SARS-CoV anti-SARS-CoV p00 p=0.0 (p=0.03 (p=0.04 (p=0.0 (p=0.02 p0000 p<0.000 000 (p<0.0001 20 p0 p=0. (p=0. p<0.00 (p<0.000 p=0 (p=0 p<0.0 (p<0.00 p= (p= p<0. (p<0.0 (p p<0 (p<0. p< (p<0 (p<

ABSTRACT The diagnosis of congenital toxoplasmosis presents limitations and therefore new options are necessary. The analysis of amniotic fluid by real-time PCR has already proved effective for confirmation of fetal infection. However, its performance in other biological samples is not clear yet. The aim of this study is to better understand the role of real-time PCR in the blood of the mother and newborn as well as in the amniotic fluid and placenta in the diagnosis of congenital toxoplasmosis. This is a descriptive cohort study of pregnant women with toxoplasmosis followed up in Rio de Janeiro, Brazil. Real-time PCR was performed in samples of maternal blood, amniotic fluid, placenta, and blood of newborns. In addition, histopathological examination of placentas was performed, and data collected from babies were collected. 116 pregnant women were followed up and 298 samples were analyzed. One (0.9%) pregnant woman presented positive PCR in the blood, 3 (3.5%) in the amniotic fluid, 1 (2.3%) in the placenta and no newborn had positive PCR in the blood. Histopathological study was suggestive of toxoplasmosis infection in 24 (49%) placentas. Six (5.2%) newborns were diagnosed with congenital toxoplasmosis, and only cases with positive PCR in the amniotic fluid had correlation of the PCR result with the diagnosis of congenital infection. Both maternal and blood samples of new-borns and placenta did not prove to be promising in the diagnosis of congenital toxoplasmosis. Further studies are needed to evaluate the real role of molecular diagnosis in other biological materials rather than the amniotic fluid. necessary realtime time However yet Janeiro Brazil Realtime Real addition 11 29 analyzed 0.9% 09 0 9 (0.9% 3.5% 35 5 (3.5% 2.3% 23 2 (2.3% 49% 49 (49% 5.2% 52 (5.2% borns 0.9 (0.9 3.5 (3.5 2.3 (2.3 4 (49 5.2 (5.2 0. (0. 3. (3. 2. (2. (4 5. (5. (0 (3 (2 ( (5