Is Sex with Older Male Partners Associated with Higher Sexual Risk Behavior Among Young Black MSM?

Participants at a sexual health clinic completed a survey with questions regarding sexual risk behavior and partner characteristics. Of 585 participants eligible for analysis, 124 reported generally having older male partners. These participants were significantly more likely to be HIV-infected (p \u3c 0.001), have four or more sex partners as a “bottom” (p = 0.04), have concurrent partners (p = 0.01), and have partners suspected of having an sexually transmitted infection (p = 0.05) than participants without older partners. With analysis restricted to HIV− individuals, risk behaviors did not differ significantly between the groups. HIV− individuals with older partners may be at increased risk of HIV infection due to increased HIV prevalence among older sexual partners and not due to increased risk behaviors with these partners

Acceptability of Condoms, Circumcision and PrEP among Young Black Men Who Have Sex with Men: A Descriptive Study Based on Effectiveness and Cost

The current study examined and compared the willingness of young Black men who have sex with men (YBMSM) to accept pre-exposure prophylaxis (PrEP), adult male circumcision, and condoms for reducing their risk of HIV acquisition. The majority (67%) reported unprotected receptive anal sex in the last six months. About three-quarters (71%) would accept using PrEP if it was 100% effective. Cost influenced PrEP acceptance with 19% indicating acceptance at $100 per month co-pay. Of those not circumcised, 50$100. About 73% of men were willing to use condoms if they were 100% effective and 50% indicated a willingness at the cost of $10 per month. The findings suggest that condom use promotion strategies should remain at the forefront of public health efforts to control HIV incidence among YBMSM

Similarities and Differences in Sexual Risk Behaviors Between Young Black MSM Who Do and Do Not Have Sex with Females

The objective of this study is to determine whether young Black MSM who also have sex with females report similar levels of sexual risk behaviors as those not having sex with females. YBMSM (N = 400) were recruited from an STI clinic, located in the Southern U.S. Men completed an audio-computer assisted self-interview and donated specimens for STI/HIV testing. Forty-three percent recently engaged in penile-vaginal sex. They were less likely to report having concurrent partners (P = .01), unprotected fellatio (P = .04), multiple partners as a bottom (P \u3c .02), any unprotected anal sex as a bottom (P \u3c .013), and any anal sex (P = .007). They were equally likely to report favorable attitudes toward serosorting (P = .80), multiple male partners as a top (P = .20), unprotected anal insertive sex with males (P = .15). Frequency of sex with males as a top (P = .61) or bottom (P = .61) did not differ. Compared to YBMSM not having sex with females, those having sex with females may be exercising greater caution

Acceptability of Condoms, Circumcision and PrEP among Young Black Men Who Have Sex with Men: A Descriptive Study Based on Effectiveness and Cost

The current study examined and compared the willingness of young Black men who have sex with men (YBMSM) to accept pre-exposure prophylaxis (PrEP), adult male circumcision, and condoms for reducing their risk of HIV acquisition. The majority (67%) reported unprotected receptive anal sex in the last six months. About three-quarters (71%) would accept using PrEP if it was 100% effective. Cost influenced PrEP acceptance with 19% indicating acceptance at $100 per month co-pay. Of those not circumcised, 50$100. About 73% of men were willing to use condoms if they were 100% effective and 50% indicated a willingness at the cost of $10 per month. The findings suggest that condom use promotion strategies should remain at the forefront of public health efforts to control HIV incidence among YBMSM

Development of Cu-SiC composite for electrical discharge machining electrode using powder metallurgy technique

In this research, composites containing 10-50 vol% SiC whiskers reinforced Cu matrix were fabricated using powder metallurgy technique. The mixtures were blended in a ball milling machine with the addition of ethanol for 2 hours at 150 rpm. The mixtures were allowed to dry in an oven at temperature of 40 °C. Then, the mixtures were uniaxially compacted into a cylindrical pallet of Φ 13.5 x 2 mm under compaction pressure of 472 MPa. It was followed by sintering in vacuum furnace at temperatures of 800-950 °C for 4 hours. The density, microhardness, electrical resistivity, thermal conductivity and microscopy analysis of the sintered composites were studied and reported in this paper

Tool life assessment in end milling titanium alloy (Ti-6Al-4V) using PCD inserts

This paper presents the investigation for assessment of tool life of PCD inserts in end milling of titanium alloy Ti-6A1-4V under dry conditions. Small central composite design (CCD) was employed to design the experiments and to develop the models which correlate tool life and the primary cutting parameters such as cutting speed, axial depth of cut and feed values. The range which is used in this study for cutting speed, axial depth of cut, and feed, are 80.5-200 m/min, 0.5-2.0 mm, and 0.05-0.15 mm/tooth, respectively. Design expert package software was employed to establish the tool life models and the adequacy of the models were verified using analysis of variance at 95% of confidence interval. From the models, it was affirmed that cutting speed has the most significant effect on tool life, followed by feed and axial depth of cut

Translational Reprogramming by eIF4E in Tamoxifen-Resistant ER+ Breast Cancer

The majority of breast cancers express the estrogen receptor (ER+) and are treated with anti-estrogen therapies, particularly the inhibitor tamoxifen. However, many women treated with tamoxifen develop resistance, leading to metastatic disease, which is responsible for the majority of breast cancer deaths. Using small molecule inhibitors, phospho-mimetic proteins, tamoxifen sensitive and resistant breast cancer cells, a patient derived tamoxifen-resistant xenograft model, and genome-wide transcription and translation studies, we show that tamoxifen resistance is mediated by selective mRNA translational reprogramming. Tamoxifen resistant translation is mediated by increased expression of translation factor eIF4E, increased mTOR activity to promote eIF4E availability, and increased MNK activity to promote eIF4E Ser209 phosphorylation. Tamoxifen re-sensitization is restored only by reducing eIF4E expression or mTOR activity and blocking MNK1-directed eIF4E phosphorylation. Of the translationally upregulated mRNAs specific to tamoxifen resistant cells, we show that Runx2, which encodes a regulator of ER signaling that antagonizes estrogen responses and promotes breast cancer metastasis, significantly increases tamoxifen resistance and restores sensitivity when silenced. Moreover, tamoxifen resistant but not sensitive patient ER+ breast cancer specimens demonstrate strongly increased levels of mTOR and MNK activity and eIF4E protein. eIF4E levels, availability and phosphorylation therefore promote tamoxifen resistance in ER+ breast cancer through translatome reprogramming

Abstract B33: Translational control pathways form a molecular hub that regulates tamoxifen resistance in ER+ breast cancer

Abstract Currently, ER+ breast cancer is treated with adjuvant antiestrogen therapies (i.e. tamoxifen and raloxifene). Despite maintaining expression of the estrogen receptor, many women treated with adjuvant therapy develop resistance several years after curative care. In fact, resistance to tamoxifen therapy is responsible for a vast majority of deaths resulting from metastatic disease. Our lab and others have shown that upregulation of the abundance and/or activity of translation initiation factors eIF4E and eIF4G1 occurs widely in advanced breast cancer, selectively upregulating translation of certain mRNAs required for survival, proliferation, and metastasis. Therefore, we hypothesized that tamoxifen resistance in ER+ breast cancer involves selective mRNA translation mediated by hyperactivation of the mTORC1 translational control pathway via regulating the availability and activity of eIF4E. Tamoxifen resistant (R) and sensitive (S) ER+ cell lines have been developed by several labs by long-term cultivation in tamoxifen and are used in my work. We define here, using the aforementioned cell lines, a molecular hub consisting of the two translational control pathways, PI3K/Akt/mTOR and MAPK/ERK/MNK which converge on translation initiation factor 4E (eIF4E) increasing its availability and activity. We show that blocking eIF4E-mediated translation was able to resensitize drug resistant cells to tamoxifen; conversely, overexpression of eIF4E, without concurrent mTORC1 hyperactivity, was not sufficient to generate resistance. Furthermore, knockdown of two genes identified from our genome-wide translation state analysis, TEX14 and RUNX2, significantly impacted drug resistance and serve as a major regulators in disease progression. Our findings demonstrate that eIF4E is a key player regulating tamoxifen resistance in ER+ disease. Citation Format: Phillip A. Geter, Robert J. Schneider. Translational control pathways form a molecular hub that regulates tamoxifen resistance in ER+ breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Translational Control of Cancer: A New Frontier in Cancer Biology and Therapy; 2016 Oct 27-30; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2017;77(6 Suppl):Abstract nr B33.</jats:p