Quantifying the Impact of Immune History and Variant on SARS-CoV-2 Viral Kinetics and Infection Rebound: A Retrospective Cohort Study

BACKGROUND: The combined impact of immunity and SARS-CoV-2 variants on viral kinetics during infections has been unclear. METHODS: We characterized 1,280 infections from the National Basketball Association occupational health cohort identified between June 2020 and January 2022 using serial RT-qPCR testing. Logistic regression and semi-mechanistic viral RNA kinetics models were used to quantify the effect of age, variant, symptom status, infection history, vaccination status and antibody titer to the founder SARS-CoV-2 strain on the duration of potential infectiousness and overall viral kinetics. The frequency of viral rebounds was quantified under multiple cycle threshold (Ct) value-based definitions. RESULTS: Among individuals detected partway through their infection, 51.0% (95% credible interval [CrI]: 48.3-53.6%) remained potentially infectious (Ct CONCLUSIONS: SARS-CoV-2 viral kinetics are partly determined by immunity and variant but dominated by individual-level variation. Since booster vaccination protects against infection, longer clearance times for BA.1-infected, boosted individuals may reflect a less effective immune response, more common in older individuals, that increases infection risk and reduces viral RNA clearance rate. The shifting landscape of viral kinetics underscores the need for continued monitoring to optimize isolation policies and to contextualize the health impacts of therapeutics and vaccines. FUNDING: Supported in part by CDC contract #200-2016-91779, a sponsored research agreement to Yale University from the National Basketball Association contract #21-003529, and the National Basketball Players Association

Reduced repair of 8-hydroxyguanine in the human breast cancer cell line, HCC1937

BACKGROUND: Breast cancer is the second leading cause of cancer deaths in women in the United States. Although the causes of this disease are incompletely understood, oxidative DNA damage is presumed to play a critical role in breast carcinogenesis. A common oxidatively induced DNA lesion is 8-hydroxyguanine (8-OH-Gua), which has been implicated in carcinogenesis. The aim of this study was to investigate the ability of HCC1937 and MCF-7 breast cancer cell lines to repair 8-OH-Gua relative to a nonmalignant human mammary epithelial cell line, AG11134. METHODS: We used oligonucleotide incision assay to analyze the ability of the two breast cancer cell lines to incise 8-OH-Gua relative to the control cell line. Liquid chromatography/mass spectrometry (LC/MS) was used to measure the levels of 8-OH-Gua as its nucleoside, 8-OH-dG in the cell lines after exposure to H(2)O(2 )followed by 30 min repair period. Protein expression levels were determined by Western blot analysis, while the hOGG1 mRNA levels were analyzed by RT-PCR. Complementation of hOGG1 activity in HCC1937 cells was assessed by addition of the purified protein in the incision assay, and in vivo by transfection of pFlagCMV-4-hOGG1. Clonogenic survival assay was used to determine sensitivity after H(2)O(2)-mediated oxidative stress. RESULTS: We show that the HCC1937 breast cancer cells have diminished ability to incise 8-OH-Gua and they accumulate higher levels of 8-OH-dG in the nuclear genome after H(2)O(2 )treatment despite a 30 min repair period when compared to the nonmalignant mammary cells. The defective incision of 8-OH-Gua was consistent with expression of undetectable amounts of hOGG1 in HCC1937 cells. The reduced incision activity was significantly stimulated by addition of purified hOGG1. Furthermore, transfection of pFlagCMV-4-hOGG1 in HCC1937 cells resulted in enhanced incision of 8-OH-Gua. HCC1937 cells are more sensitive to high levels of H(2)O(2 )and have up-regulated SOD1 and SOD2. CONCLUSION: This study provides evidence for inefficient repair of 8-OH-Gua in HCC1937 breast cancer cell line and directly implicates hOGG1 in this defect

A 17 mW 33 dBm IB-OIP3 0.5-1.5 GHz Bandwidth TIA Based on an Inductor-Stabilized OTA

A highly linear Trans-Impedance Amplifier (TIA) for 5G New Radio mobile communication receivers is presented. The TIA has a cut-off frequency programmable from 500 MHz up to 1.5 GHz. The TIA is based on a Feed-Forward compensated amplifier. To ensure stability while achieving high bandwidth and low power, an inductor is used inside the feed-forward stage. A test chip has been realized in 28 nm CMOS technology. The TIA achieves an In-band O1P3 of 32.9 dBm and the output integrated noise from 20 MHz to 1.5 GHz is lower than 300 mu V-rms with a power dissipation of 17 mW

A 17-mW 0.5-1.5-GHz Bandwidth TIA Based on an Inductor-Stabilized OTA with 35-42-dBm In-Band IIP3

A transimpedance amplifier (TIA) is presented for 5G and future mobile standards. The bandwidth of the TIA can be programmed from 500 MHz to 1.5 GHz. The operational transconductance amplifier (OTA) is designed combining feedforward compensation and inductive peaking, to ensure loop stability and obtain high loop gain with low-power dissipation. TSMC 28-nm HPC technology was used to implement a test chip. With a power dissipation of 17 mW, the TIA achieves an in-band IIP3 ranging from 35 to 42 dBm and output integrated noise of 300 μ Vrms

Oxidative DNA damage: mechanisms, mutation, and disease

ABSTRACT Oxidative DNA damage is an inevitable consequence of cellular metabolism, with a propensity for increased levels following toxic insult. Although more than 20 base lesions have been identified, only a fraction of these have received appreciable study, most notably 8-oxo-2�deoxyguanosine. This lesion has been the focus of intense research interest and been ascribed much importance, largely to the detriment of other lesions. The present work reviews the basis for the biological significance of oxidative DNA damage, drawing attention to the multiplicity of proteins with repair activities along with a number of poorly considered effects of damage. Given the plethora of (often contradictory) reports describing pathological conditions in which levels of oxidative DNA damage have been measured, this review critically addresses the extent to which the in vitro significance of such damage has relevance for the pathogenesis of disease. It is suggested that some shortcomings associated with biomarkers, along with gaps in our knowledge, may be responsible for the failure to produce consistent and definitive results when applied to understanding the role of DNA damage in disease, highlighting the need for further studies.—Cooke, M. S., Evans, M. D.

A retrospective study of the pattern of sexually transmitted diseases in teenagers attending sexually transmitted disease clinic during a 7-year period at a tertiary care centre

Background: Adolescent period corresponds to the age group of 10-15 years. While teenage period, which corresponds to 13-19 year of age group, is the stage of psychosocial development. More and more young people are becoming sexually active in their mid-teens making them vulnerable to contracting the STDs. Adolescents especially in urban areas have favorable attitudes toward premarital and extramarital sex. Material and Methods: This is a retrospective study conducted at tertiary care center. Data regarding STD in teenagers (13-19 year) and their sexual behavior from January 2009 to December 2015 was collected from STI clinic. Result: Total number of adolescent attended STI clinic was 381,out of which 200 were male and 181 were female. Most common STD in female was VVC and in male was nodular scabies. out of 381 patients 155 male and 93 female had confessed about indulging in sexual activity.10 patients were tested positive for HIV and 11 patients were tested positive for syphilis. Conclusion: There is increasing incidence & prevalence of STDs in adolescents due to risky sexual behavior. It is essential to include sex education in teaching methods