Cataclysmic Variables from Sloan Digital Sky Survey V -- the search for period bouncers continues

SDSS-V is carrying out a dedicated survey for white dwarfs, single and in binaries, and we report the analysis of the spectroscopy of cataclysmic variables (CVs) and CV candidates obtained during the final plug plate observations of SDSS. We identify eight new CVs, spectroscopically confirm 53 and refute eleven published CV candidates, and we report 21 new or improved orbital periods. Combined with previously published data, the orbital period distribution of the SDSS-V CVs does not clearly exhibit a period gap. This is consistent with previous findings that spectroscopically identified CVs have a larger proportion of short-period systems compared to samples identified from photometric variability. Remarkably, despite a systematic search, we find very few period bouncers. We estimate the space density of period bouncers to be $\simeq0.2\times10^{-6}\,\mathrm{pc}^{-3}$, i.e. they represent only a few per cent of the total CV population. This suggests that during their final phase of evolution, CVs either destroy the donor, e.g. via a merger, or that they become detached and cease mass transfer.Comment: Submitted to MNRA

Molecular targeting of prostate cancer cells by a triple drug combination down-regulates integrin driven adhesion processes, delays cell cycle progression and interferes with the cdk-cyclin axis

Background: Single drug use has not achieved satisfactory results in the treatment of prostate cancer, despite application of increasingly widespread targeted therapeutics. In the present study, the combined impact of the mammalian target of rapamycin (mTOR)-inhibitor RAD001, the dual EGFr and VGEFr tyrosine kinase inhibitor AEE788 and the histone deacetylase (HDAC)-inhibitor valproic acid (VPA) on prostate cancer growth and adhesion in vitro was investigated. Methods: PC-3, DU-145 and LNCaP cells were treated with RAD001, AEE788 or VPA or with a RAD-AEE-VPA combination. Tumor cell growth, cell cycle progression and cell cycle regulating proteins were then investigated by MTT-assay, flow cytometry and western blotting, respectively. Furthermore, tumor cell adhesion to vascular endothelium or to immobilized extracellular matrix proteins as well as migratory properties of the cells was evaluated, and integrin alpha and beta subtypes were analyzed. Finally, effects of drug treatment on cell signaling pathways were determined. Results: All drugs, separately applied, reduced tumor cell adhesion, migration and growth. A much stronger anti-cancer effect was evoked by the triple drug combination. Particularly, cdk1, 2 and 4 and cyclin B were reduced, whereas p27 was elevated. In addition, simultaneous application of RAD001, AEE788 and VPA altered the membranous, cytoplasmic and gene expression pattern of various integrin alpha and beta subtypes, reduced integrin-linked kinase (ILK) and deactivated focal adhesion kinase (FAK). Signaling analysis revealed that EGFr and the downstream target Akt, as well as p70S6k was distinctly modified in the presence of the drug combination. Conclusions: Simultaneous targeting of several key proteins in prostate cancer cells provides an advantage over targeting a single pathway. Since strong anti-tumor properties became evident with respect to cell growth and adhesion dynamics, the triple drug combination might provide progress in the treatment of advanced prostate cancer

Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women

Background: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. Methods: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. Results: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. Conclusions: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure

Time in Service and Resilience in Active Military Personnel during the COVID-19 Pandemic: A Cross-Sectional Study in Northern Peru

Greater occupational exposure may have a positive effect on the development of resilience. We aimed to determine the association between working time and resilience in Peruvian military personnel during the COVID-19 pandemic. A secondary data analysis was performed including 586 records of military personnel who supported the health emergency during the second epidemic wave in Lambayeque, Peru. Resilience was measured with the short form of the Connor-Davidson Resilience Scale (CD-RISC). Working time and other relevant covariates were collected by self-report. Generalized linear models were used. The mean resilience score was 22.18 and 43.2% scored high for resilience. Participants reported that they are strong individuals when facing difficulties (42.3%), are able to handle unpleasant feelings (40.3%), and achieve their goals despite obstacles (40.4%). Working more than 18 months was associated with a 35% higher prevalence of high resilience (PR: 1.35; 95% CI: 1.05–1.75). In conclusion, a notable number of military personnel experienced high levels of resilience during the pandemic. Working time may have played an important role in the development of this ability. Our findings could help guide the deployment and organization of the military in health emergency support missions

Perception of possible sars-cov-2 infection and associated complications in seven labor sectors in peru

Objective: To determine the perception of possible infection caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) and associated complications according to the labor sector in Peru. Methods: We performed an observational, cross sectional, and secondary data analysis. The study had three dependent variables that were obtained from a locally validated questionnaire, in which it is asked whether the professionals had the perception that they could be infected with SARS-CoV-2 at work, or could transmit the virus to their family/friends, and regarding the possibility of complications related to the infection. Results: Of the 2843 workers participating in the study, those in the health sector perceived that they were more likely to be infected at work. In the multivariate analysis, adjusted for four variables, health sector workers also perceived that they could be infected more frequently at work (adjusted prevalence ratio (aPR): 1.74; 95% confidence interval (CI): 1.40-2.15; p <0.001). These professionals, moreover, perceived that they could transmit the virus to their family/friends (aPR: 0.76; 95% CI: 0.63-0.92; p = 0.005) or that there would be complications resulting from the infection (aPR: 0.59; 95% CI: 0.48-0.73; p <0.001). On the other hand, engineering sector workers were the ones who had a greater perception that they could infect their family/friends (aPR: 1.95; 95% CI: 1.20-3.20; p = 0.007), while workers from other sectors perceived that they could have more chances of complications from the infection (aPR: 1.17; 95% CI: 1.05-1.30; p = 0.006). Conclusion: The health sector may be the most vulnerable in this context, which is why occupational health teams should develop and implement specific surveillance plans to prevent and reduce the number of coronavirus disease 2019 (COVID-19) cases among healthcare workers

Highly mutagenic exocyclic DNA adducts are substrates for the human nucleotide incision repair pathway

Background: Oxygen free radicals induce lipid peroxidation (LPO) that damages and breaks polyunsaturated fatty acids in cell membranes. LPO-derived aldehydes and hydroxyalkenals react with DNA leading to formation of etheno(ε)-bases including 1,N6-ethenoadenine (εA) and 3,N4-ethenocytosine (εC). The εA and εC residues are highly mutagenic in mammalian cells and eliminated in the base excision repair (BER) pathway and/or by AlkB family proteins in the direct damage reversal process. BER initiated by DNA glycosylases is thought to be the major pathway for the removal of non-bulky endogenous base damage. Alternatively, in the nucleotide incision repair (NIR) pathway, the apurinic/apyrimidinic (AP) endonucleases can directly incise DNA duplex 5’ to a damaged base in a DNA glycosylase-independent manner. Methodology/Principal Findings: Here, we characterized the substrate specificity of human major AP endonuclease 1, APE1, towards εA, εC, thymine glycol (Tg) and 7,8-dihydro-8-oxoguanine (8oxoG) residues when present in duplex DNA. APE1 cleaves oligonucleotide duplexes containing εA, εC and Tg, but not those containing 8oxoG. The activity depends strongly on sequence context. The apparent kinetic parameters of the reactions suggest that APE1 has high affinity to DNA containing ε-bases but cleaves DNA duplex at an extremely slow rate. Consistent with this observation, the oligonucleotide duplexes containing an ε-base strongly inhibit AP site nicking activity of APE1 with IC50 values in the range of 5-10 nM. MALDI-TOF MS analysis of the reaction products demonstrated that APE1-catalyzed cleavage of εA•T and εC•G duplexes generates as expected DNA fragments containing 5’-terminal ε-base residue. Conclusions/Significance: The fact that ε-bases and Tg in duplex DNA are recognized and cleaved by APE1 in vitro, suggest that NIR may act as a backup pathway to BER one to remove a large variety of genotoxic base lesions in human cells