Thirdhand cigarette smoke (THS) is a newly described toxin that lingers in the indoor environment long after cigarettes have been extinguished. Emerging results from both cellular and animal model studies suggest that THS is a potential human health hazard. DNA damage derived from THS exposure could have genotoxic consequences that would lead to the development of diseases. However, THS exposure-induced interference with fundamental DNA transactions such as replication and transcription, and the role of DNA repair in ameliorating such effects, remain unexplored. Here, we found that THS exposure increased the percentage of cells in S-phase, suggesting impaired S-phase progression. Key DNA damage response proteins including RPA, ATR, ATM, CHK1, and BRCA1 were activated in lung cells exposed to THS, consistent with replication stress. In addition, THS exposure caused increased 53BP1 foci, indicating DNA double-strand break induction. Consistent with these results, we observed increased micronuclei formation, a marker of genomic instability, in THS-exposed cells. Exposure to THS also caused a significant increase in phosphorylated RNA Polymerase II engaged in transcription elongation, suggesting an increase in transcription-blocking lesions. In agreement with this conclusion, ongoing RNA synthesis was very significantly reduced by THS exposure. https://www.selleckchem.com/products/wz-811.html Loss of nucleotide excision repair exacerbated the reduction in RNA synthesis, suggesting that bulky DNA adducts formed by THS are blocks to transcription. The adverse impact on both replication and transcription supports genotoxic stress as a result of THS exposure, with important implications for both cancer and other diseases. © 2020 Wiley Periodicals, Inc.BACKGROUND The serum alanine aminotransferase (ALT) level is a critical parameter for evaluating liver injury in non-alcoholic fatty liver disease (NAFLD). However, the currently accepted upper limits of normal (ULN) for serum ALT (ULN-ALT) are debated, as they may be excessively high. METHODS A total of 1638 children aged 6-16 years, comprising 507 children with normal BMI (500 healthy children and 7 children with NAFLD), 199 overweight children, and 932 obese children, were included in the analysis. We re-evaluated the ULN-ALT in 500 healthy Chinese children using the 95th percentiles of serum ALT levels as revised ULN-ALT. Fatty liver was identified by ultrasound examination. RESULTS Significant positive correlations between serum ALT levels and body mass index (BMI) were detected in overweight boys (r = .399, P 40, 20-40, and ≤20 U/L, respectively. CONCLUSION Serum ALT levels significantly correlated with abnormal BMI values in children, suggesting a rigorous BMI threshold is needed to establish the cutoffs for serum ULN-ALT in children. Besides, the revised serum ULN-ALT can uncover mild liver injury in obese children with NAFLD. © 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.BACKGROUND Ultrasonography can improve disease severity assessment in hidradenitis suppurativa (HS) patients. The use of pre-operative ultrasonography could improve surgical outcomes in HS patients. OBJECTIVES 1) To assess changes in the projected skin excised area after the use of pre-operative ultrasonography, 2) To explore the clinical factors potentially associated with inaccurate clinical surgical delimitation, and 3) To compare recurrence rates after pre-operative ultrasound vs clinical surgical margin delimitation at week 24. METHODS Cohort study. Patient candidates for surgical treatment by wide excision and healing by secondary intention with a clinical projected skin excised area equal to or larger than 15 cm2 were included. The main variables of interest were the clinical and ultrasound projected skin excised area and surgical recurrence. RESULTS Pre-operative ultrasound surgical margin delimitation increased the mean excised area by 3.67 (SD 0.86) cm2 , p=0.004. The Bland Altman plot showed that in 65% of surgical procedures the use of ultrasonography increased the projected skin excised area. Higher IHS4 scores, BMI, male sex and Hurley stage II vs III all increased the difference between clinical and ultrasound surgical delimitation. At week 24, the recurrence rate in the surgical clinical delimitation cohort was 30% compared to 10% in the cohort with preoperative ultrasonography (p=0.10). CONCLUSIONS Preoperative ultrasonography improves surgical margin delimitation and can lower recurrence rates at 24 weeks in HS patients. Potential risk factors for inaccurate clinical surgical delimitation are obesity, male sex, Hurley II stage and elevated IHS4 scores, so special attention should be given to these patients when ultrasonography is not available and surgical delimitation is based only on clinical examination. This article is protected by copyright. All rights reserved.We present a case of rare double drainage of total anomalous pulmonary venous connection, which was diagnosed on a dual-source CT scanner. This case also highlights the critical role of volume-rendered images for preoperative planning. © 2020 Wiley Periodicals, Inc.Holmium laser enucleation of the prostate (HoLEP) is a minimally invasive and size-independent treatment for benign prostatic hyperplasia with excellent long-term surgical outcome. Considered difficult to learn, different modifications of the technique have been proposed in the last 21 years to overcome the most common problems encountered during this procedure. We present a step-by-step technique including the reasons and advantages of each modification we have progressively adopted until we evolved into our totally en-bloc no-touch low-power HoLEP. © 2020 Blackwell Verlag GmbH.Diverse workforces and inclusive workplaces improve productivity, innovation and overall quality-of-care for all patients (2,3), increase public trust in medical research (4), and are generally good for business (5). Unfortunately, orthopaedics lags behind other biomedical fields in the recruitment of women and underrepresented minorities into training programs and faculty ranks (6-8) and focused recruitment efforts have not reduced the gender, racial or ethnic gaps in orthopaedic residency programs (8). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Thirdhand cigarette smoke (THS) is a newly described toxin that lingers in the indoor environment long after cigarettes have been extinguished. Emerging results from both cellular and animal model studies suggest that THS is a potential human health hazard. DNA damage derived from THS exposure could have genotoxic consequences that would lead to the development of diseases. However, THS exposure-induced interference with fundamental DNA transactions such as replication and transcription, and the role of DNA repair in ameliorating such effects, remain unexplored. Here, we found that THS exposure increased the percentage of cells in S-phase, suggesting impaired S-phase progression. Key DNA damage response proteins including RPA, ATR, ATM, CHK1, and BRCA1 were activated in lung cells exposed to THS, consistent with replication stress. In addition, THS exposure caused increased 53BP1 foci, indicating DNA double-strand break induction. Consistent with these results, we observed increased micronuclei formation, a marker of genomic instability, in THS-exposed cells. Exposure to THS also caused a significant increase in phosphorylated RNA Polymerase II engaged in transcription elongation, suggesting an increase in transcription-blocking lesions. In agreement with this conclusion, ongoing RNA synthesis was very significantly reduced by THS exposure. https://www.selleckchem.com/products/wz-811.html Loss of nucleotide excision repair exacerbated the reduction in RNA synthesis, suggesting that bulky DNA adducts formed by THS are blocks to transcription. The adverse impact on both replication and transcription supports genotoxic stress as a result of THS exposure, with important implications for both cancer and other diseases. © 2020 Wiley Periodicals, Inc.BACKGROUND The serum alanine aminotransferase (ALT) level is a critical parameter for evaluating liver injury in non-alcoholic fatty liver disease (NAFLD). However, the currently accepted upper limits of normal (ULN) for serum ALT (ULN-ALT) are debated, as they may be excessively high. METHODS A total of 1638 children aged 6-16 years, comprising 507 children with normal BMI (500 healthy children and 7 children with NAFLD), 199 overweight children, and 932 obese children, were included in the analysis. We re-evaluated the ULN-ALT in 500 healthy Chinese children using the 95th percentiles of serum ALT levels as revised ULN-ALT. Fatty liver was identified by ultrasound examination. RESULTS Significant positive correlations between serum ALT levels and body mass index (BMI) were detected in overweight boys (r = .399, P 40, 20-40, and ≤20 U/L, respectively. CONCLUSION Serum ALT levels significantly correlated with abnormal BMI values in children, suggesting a rigorous BMI threshold is needed to establish the cutoffs for serum ULN-ALT in children. Besides, the revised serum ULN-ALT can uncover mild liver injury in obese children with NAFLD. © 2020 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.BACKGROUND Ultrasonography can improve disease severity assessment in hidradenitis suppurativa (HS) patients. The use of pre-operative ultrasonography could improve surgical outcomes in HS patients. OBJECTIVES 1) To assess changes in the projected skin excised area after the use of pre-operative ultrasonography, 2) To explore the clinical factors potentially associated with inaccurate clinical surgical delimitation, and 3) To compare recurrence rates after pre-operative ultrasound vs clinical surgical margin delimitation at week 24. METHODS Cohort study. Patient candidates for surgical treatment by wide excision and healing by secondary intention with a clinical projected skin excised area equal to or larger than 15 cm2 were included. The main variables of interest were the clinical and ultrasound projected skin excised area and surgical recurrence. RESULTS Pre-operative ultrasound surgical margin delimitation increased the mean excised area by 3.67 (SD 0.86) cm2 , p=0.004. The Bland Altman plot showed that in 65% of surgical procedures the use of ultrasonography increased the projected skin excised area. Higher IHS4 scores, BMI, male sex and Hurley stage II vs III all increased the difference between clinical and ultrasound surgical delimitation. At week 24, the recurrence rate in the surgical clinical delimitation cohort was 30% compared to 10% in the cohort with preoperative ultrasonography (p=0.10). CONCLUSIONS Preoperative ultrasonography improves surgical margin delimitation and can lower recurrence rates at 24 weeks in HS patients. Potential risk factors for inaccurate clinical surgical delimitation are obesity, male sex, Hurley II stage and elevated IHS4 scores, so special attention should be given to these patients when ultrasonography is not available and surgical delimitation is based only on clinical examination. This article is protected by copyright. All rights reserved.We present a case of rare double drainage of total anomalous pulmonary venous connection, which was diagnosed on a dual-source CT scanner. This case also highlights the critical role of volume-rendered images for preoperative planning. © 2020 Wiley Periodicals, Inc.Holmium laser enucleation of the prostate (HoLEP) is a minimally invasive and size-independent treatment for benign prostatic hyperplasia with excellent long-term surgical outcome. Considered difficult to learn, different modifications of the technique have been proposed in the last 21 years to overcome the most common problems encountered during this procedure. We present a step-by-step technique including the reasons and advantages of each modification we have progressively adopted until we evolved into our totally en-bloc no-touch low-power HoLEP. © 2020 Blackwell Verlag GmbH.Diverse workforces and inclusive workplaces improve productivity, innovation and overall quality-of-care for all patients (2,3), increase public trust in medical research (4), and are generally good for business (5). Unfortunately, orthopaedics lags behind other biomedical fields in the recruitment of women and underrepresented minorities into training programs and faculty ranks (6-8) and focused recruitment efforts have not reduced the gender, racial or ethnic gaps in orthopaedic residency programs (8). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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