Low Self-Perceived Need for PrEP and Behavioral Indications of MSM Who Recently Refused Daily PrEP: A Mixed Methods Study in Three U.S. Cities.

Pre-exposure prophylaxis (PrEP) reduces sexual risk for HIV transmission by 99% when used appropriately, but remains underutilized among gay, bisexual, and other men who have sex with men (MSM). In this mixed-method study, we describe reasons for PrEP refusal associated with low self-perceived need for PrEP among MSM who recently declined daily oral PrEP when offered by a provider. Data are from a quantitative behavioral survey of MSM (N = 93) living in Atlanta, Chicago, and Raleigh-Durham, who also either responded to an in-depth interview (n = 51) or participated in one of 12 focus groups (n = 42). Themes of low self-perceived need for PrEP were: low self-perceived risk for HIV acquisition (33% of respondents); confidence in remaining HIV-negative (35%); using condoms (81%); limiting number of partners and choosing partners carefully (48%); asking partners about their HIV status before having sex (45%); engaging in safer sexual positions or oral sex (28%); being in a monogamous relationship or exclusivity with one partner (26%); and regular HIV testing (18%). Low self-perceived risk for HIV acquisition and high confidence in other prevention strategies were important factors related to low self-perceived need in MSM refusing daily oral PrEP when offered. Providers should continue to discuss the benefits of PrEP as a safe and highly effective option for HIV prevention.

RESUMEN: La profilaxis pre-exposición (PrEP) reduce el riesgo de transmisión sexual por el VIH en un 99% cuando se utiliza apropiadamente, pero sigue siendo subutilizada entre hombres gais, bisexuales y otros hombres que tienen sexo con hombres (HSH). En este estudio de método mixto, describimos los motivos del rechazo de la PrEP asociados a la baja necesidad autopercibida de la PrEP entre los HSH que recientemente rechazaron la PrEP oral diaria, cuando fue ofrecida por un proveedor de salud. Los datos provienen de una encuesta cuantitativa de comportamiento de los HSH (N = 93) que viven en Atlanta, Chicago y Raleigh-Durham, quienes también respondieron a una entrevista en profundidad (n = 51) o participaron en uno de los 12 grupos focales (n = 42). Los temas de baja necesidad autopercibida del uso de la PrEP fueron: el bajo riesgo auto percibido de contraer el VIH (33% de los encuestados); la confianza en seguir siendo VIH negativo (35%); utilizar condones (81%); limitar el número de parejas sexuales y elegir las parejas cuidadosamente (48%); preguntar a sus parejas sobre su estado de VIH antes de tener relaciones sexuales (45%); participar en posiciones sexuales más seguras o sexo oral (28%); estar en relación monógama o de exclusividad con una sola pareja (26%); y hacerse pruebas del VIH regularmente (18%). El bajo riesgo autopercibido de contraer el VIH y la alta confianza en otras estrategias de prevención fueron factores importantes relacionados con la baja necesidad autopercibida en los HSH que rechazaron la PrEP oral diaria cuando se les ofreció. Los proveedores de salud deben continuar el diálogo sobre los beneficios de la PrEP como una opción segura y altamente eficaz para la prevención del VIH.

Racial/ethnic disparities in estimated undiagnosed HIV infection among adolescents and adults in the United States, 2017-2021.

In 2021, there were an estimated 153 500 persons aged at least 13 years with undiagnosed HIV infection. Estimated rates among Black/African American, Hispanic/Latino, and White persons were used to assess disparity trends from 2017 to 2021. Rates decreased across two absolute and relative disparity measures. Despite these declines, Black and Hispanic persons had rates 8.3 and 4.2 times the rate of White persons in 2021. Increased testing and innovative efforts are needed to address HIV-related disparities.

Progress Toward Equitable Mpox Vaccination Coverage: A Shortfall Analysis - United States, May 2022-April 2023.

More than 30,000 monkeypox (mpox) cases were reported in the United States during the 2022 multinational outbreak; cases disproportionately affected gay, bisexual, and other men who have sex with men (MSM). Substantial racial and ethnic disparities in incidence were also reported (1). The national mpox vaccination strategy* emphasizes that efforts to administer the JYNNEOS mpox vaccine should be focused among the populations at elevated risk for exposure to mpox (2). During May 2022-April 2023, a total of 748,329 first JYNNEOS vaccine doses (of the two recommended) were administered in the United States.† During the initial months of the outbreak, lower vaccination coverage rates among racial and ethnic minority groups were reported (1,3); however, after implementation of initiatives developed to expand access to mpox vaccination,§ coverage among racial and ethnic minority groups increased (1,4). A shortfall analysis was conducted to examine whether the increase in mpox vaccination coverage was equitable across all racial and ethnic groups (5). Shortfall was defined as the percentage of the vaccine-eligible population that did not receive the vaccine (i.e., 100% minus the percentage of the eligible population that did receive a first dose). Monthly mpox vaccination shortfalls were calculated and were stratified by race and ethnicity; monthly percent reductions in shortfall were also calculated compared with the preceding month's shortfall (6). The mpox vaccination shortfall decreased among all racial and ethnic groups during May 2022-April 2023; however, based on analysis of vaccine administration data with race and ethnicity reported, 66.0% of vaccine-eligible persons remained unvaccinated at the end of this period. The shortfall was largest among non-Hispanic Black or African American (Black) (77.9%) and non-Hispanic American Indian or Alaska Native (AI/AN) (74.5%) persons, followed by non-Hispanic White (White) (66.6%) and Hispanic or Latino (Hispanic) (63.0%) persons, and was lowest among non-Hispanic Asian (Asian) (38.5%) and non-Hispanic Native Hawaiian and other Pacific Islander (NH/OPI) (43.7%) persons. The largest percentage decreases in the shortfall were achieved during August (17.7%) and September (8.5%). However, during these months, smaller percentage decreases were achieved among Black persons (12.2% and 4.9%, respectively), highlighting the need for a focus on equity for the entirety of a public health response. Achieving equitable progress in JYNNEOS vaccination coverage will require substantial decreases in shortfalls among Black and AI/AN persons.

Intersectional Discrimination in HIV Healthcare Settings Among Persons with Diagnosed HIV in the United States, Medical Monitoring Project, 2018-2019.

Experiences with stigma and discrimination in healthcare settings are associated with negative health outcome for persons with HIV (PWH). PWH may experience discrimination due to the intersection of multiple marginalized social identities. Describing these experiences is important for informing interventions and strategies to reduce stigma and discrimination. We report experiences with discrimination in HIV healthcare settings attributed to multiple characteristics, e.g., sexual orientation, race/ethnicity, income, or social class, and/or injection drug use, among a nationally representative sample of persons with diagnosed HIV in the United States using data from the Medical Monitoring Project (MMP). We calculated weighted prevalences and associated 95% confidence intervals for any discrimination and discrimination attributed to multiple characteristics (intersectional discrimination). Among those experiencing discrimination, nearly 1 in 4 persons reported intersectional discrimination, with a higher burden among key populations of focus for HIV prevention and treatment. Discrimination was attributed to HIV status (62.5%), sexual orientation (60.4%), and race/ethnicity (54.3%). Persons who experienced intersectional discrimination were less likely to have a regular HIV care provider, have trust in HIV care or treatment information from healthcare providers, and be antiretroviral treatment or HIV care visit adherent. Future studies should explore methods to operationalize and assess experiences with intersectional stigma and discrimination and use the outcomes to inform qualitative research that provides more context and a deeper understanding of experiences with intersectional discrimination among PWH.

Racial and Ethnic Disparities in Mpox Cases and Vaccination Among Adult Males - United States, May-December 2022.

As of December 31, 2022, a total of 29,939 monkeypox (mpox) cases* had been reported in the United States, 93.3% of which occurred in adult males. During May 10-December 31, 2022, 723,112 persons in the United States received the first dose in a 2-dose mpox (JYNNEOS)† vaccination series; 89.7% of these doses were administered to males (1). The current mpox outbreak has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) and racial and ethnic minority groups (1,2). To examine racial and ethnic disparities in mpox incidence and vaccination rates, rate ratios (RRs) for incidence and vaccination rates and vaccination-to-case ratios were calculated, and trends in these measures were assessed among males aged ≥18 years (males) (3). Incidence in males in all racial and ethnic minority groups except non-Hispanic Asian (Asian) males was higher than that among non-Hispanic White (White) males. At the peak of the outbreak in August 2022, incidences among non-Hispanic Black or African American (Black) and Hispanic or Latino (Hispanic) males were higher than incidence among White males (RR = 6.9 and 4.1, respectively). Overall, vaccination rates were higher among males in racial and ethnic minority groups than among White males. However, the vaccination-to-case ratio was lower among Black (8.8) and Hispanic (16.2) males than among White males (42.5) during the full analytic period, indicating that vaccination rates among Black and Hispanic males were not proportionate to the elevated incidence rates (i.e., these groups had a higher unmet vaccination need). Efforts to increase vaccination among Black and Hispanic males might have resulted in the observed relative increased rates of vaccination; however, these increases were only partially successful in reducing overall incidence disparities. Continued implementation of equity-based vaccination strategies is needed to further increase vaccination rates and reduce the incidence of mpox among all racial and ethnic groups. Recent modeling data (4) showing that, based on current vaccination coverage levels, many U.S. jurisdictions are vulnerable to resurgent mpox outbreaks, underscore the need for continued vaccination efforts, particularly among racial and ethnic minority groups.

Emotional distress among adolescents living with perinatal HIV in India: examining predictors and their mediating and moderating effects.

BACKGROUND: Development of emotional distress (ED) among adolescents living with perinatally acquired HIV (ALPHIV) affects their adherence behaviour and social and psychological functioning. Data on stressors among ALPHIV demonstrates the gap on the predictors of ED experienced by 'perinatally infected ALHIV' in the Indian socio-cultural milieu. This study aimed to identify the predictors of ED and examine their mediating and moderating role in the development of ED among Indian ALPHIV. METHODS: Utilizing the sequential exploratory mixed-methods design, 43 qualitative interviews were conducted with ALPHIV, parents/guardians, and health care providers, followed by the cross-sectional survey among 100 ALPHIV (10-19 years). The distress subscale of the Weinberger Adjustment Inventory was used to measure ED. Qualitative data, analyzed using grounded theory were utilized to develop a survey tool. Bivariate and regression analyses were conducted to identify predictors of ED. Mediation and moderation models were tested to examine underlying mechanisms associated with ED. The study was approved by the institutional ethics committee. RESULTS: Strong parental control, compulsive asexuality, perceived negatively different from peers, and anger toward parents were the major themes emerging from the qualitative component which eventually led to survey tool domains viz., HIV awareness, parental control, hypervigilance, adolescent-parent relationship, adolescent-parent communication, body image and perceived negatively different from peers (PNDP). Quantitative analysis indicated high ED among ALPHIV and ED was significantly associated with PNDP, anger, body image, and hypervigilance. The relationship between PNDP and ED was significantly mediated by anger, and moderated by body image and hypervigilance. CONCLUSIONS: The study stresses the need for early mental health interventions for Indian ALPHIV before an ALPHIV develops ED. Focused counseling on anger assessment, body image issues, and self-perception is critical for leading a 'normal' life by ALPHIV. Besides, skill building of primary caregivers is recommended to draw a line between protection and overprotection.

Pre-exposure prophylaxis in the era of emerging methods for men who have sex with men in the USA: the HIV Prevention Cycle of Care model.

Expanding on previous work, we present an HIV Prevention Cycle of Care model to facilitate understanding of the complexity of issues involved in pre-exposure prophylaxis implementation for gay, bisexual, and other men who have sex with men (MSM) in the USA, including individual, client-provider, and overarching issues such as health equity, stigma, and prevention nomenclature. The HIV prevention cycle of care applies to MSM who test negative for HIV. The Prevention Cycle of Care model includes seven steps: prevention knowledge, prevention self-awareness and preferences, prevention motivation, health-care access and cost, provider issues, adherence and persistence, and periodic reassessment and adjustment. HIV prevention is complex in an era of emerging multiple modalities, and more research is needed to successfully implement pre-exposure prophylaxis options over time and across diverse communities of MSM who are sexually active.

Brief Report: Refusal of Daily Oral PrEP: Implementation Considerations and Reported Likelihood of Using Various HIV Prophylaxis Products in a Diverse Sample of MSM.

BACKGROUND: An important subgroup of gay, bisexual, and other men who have sex with men (MSM) with behavioral indications refuse daily oral pre-exposure prophylaxis (PrEP) when recommended by a provider. Emerging HIV prophylaxis products (eg, injectable, event-driven) offer more options to MSM who refuse daily PrEP. In this article, we assess reasons for refusal and likelihood to use various products among MSM who refused PrEP. METHODS: MSM who reported anal sex without condoms or PrEP and refused daily oral PrEP in the past 6 months were recruited through clinics, community venues, and online in Atlanta, Chicago, and Raleigh-Durham. Men were asked their main reason for recently refusing daily PrEP and likelihood of using various PrEP options in the future. Bivariate and multivariable regression models were used to estimate associations. RESULTS: MSM (n = 93; 70% Black, 48% age 18-29 years) reported their main reason for refusing daily PrEP were potential side effects (35%), a daily pill regimen (22%), and not having enough information (18%). Reported likelihood of using PrEP products was 58% for penile gel, 54% for event-driven oral, 52% for injectable, and 50% for daily PrEP. MSM who reported daily regimen as the main reason for refusing PrEP had greater odds of likelihood to use an injectable [adjusted odds ratio (AOR) = 5.21, 95% confidence interval (CI): 1.32 to 20.52]. Younger men (18-29 vs 30+ years) had greater odds of likelihood to use condoms (AOR = 3.40, 95% CI: 1.15 to 10.04) and daily PrEP (AOR = 2.76, 95% CI: 1.06 to 7.16); there were no product preference differences by race. CONCLUSION: Most men who refused daily PrEP indicated likelihood of using some form of PrEP in the future.

Stigma, Discrimination, and Mental Health Outcomes Among Transgender Women With Diagnosed HIV Infection in the United States, 2015-2018.

OBJECTIVE: Transgender women with diagnosed HIV experience social and structural factors that could negatively affect their overall health and HIV-related health outcomes. We describe estimates from the Centers for Disease Control and Prevention Medical Monitoring Project (MMP) of sociodemographic characteristics, HIV stigma, discrimination, and mental health outcomes among transgender women with diagnosed HIV. METHODS: We analyzed pooled data of all transgender women with diagnosed HIV (N = 217) from the 2015 through 2018 MMP cycles. We reported unweighted frequencies, weighted percentages, and 95% CIs for all characteristics. We post-stratified data to known population totals by age, race and ethnicity, and sex at birth from the National HIV Surveillance System. RESULTS: Approximately 46% of transgender women with diagnosed HIV identified as Black or African American, 67% lived at or below the federal poverty level, 18% had experienced homelessness in the past year, 26% experienced mild to severe symptoms of depression, 30% experienced mild to severe anxiety symptoms, 32% reported physical violence by an intimate partner, and 30% reported forced sex during their lifetime. Despite 80% being very satisfied with their current HIV care, 94% experienced current HIV stigma and 20% experienced health care-related discrimination since being diagnosed with HIV. Among transgender women with diagnosed HIV who experienced discrimination, 46% and 51% experienced health care discrimination attributed to their gender and sexual orientation or sexual practices, respectively. CONCLUSIONS: Our findings underscore a need to address unmet ancillary services, such as housing, intimate partner violence, and mental health needs, and the need for strategies to reduce experiences with HIV stigma and discrimination in care for transgender women with diagnosed HIV in the United States.

HIV care outcomes among transgender persons with HIV infection in the United States, 2006-2021.

OBJECTIVES: HIV prevalence is an estimated 14% among transgender women (TW) and 3% among transgender men (TM). HIV care is vital for viral suppression but is hindered by transphobia and HIV stigma. We assessed HIV care outcomes among transgender persons (TG) with HIV in the United States. DESIGN: Systematic review and meta-analysis of peer-reviewed journal articles. METHODS: We searched multiple electronic databases and Centers for Disease Control and Prevention's HIV Prevention Research Synthesis database for 2006-September 2020. Eligible reports were US-based studies that included TG and reported HIV care outcomes. Random-effects models were used to calculate HIV care outcome rates. The protocol is registered with PROSPERO (CRD42018079564). RESULTS: Few studies reported outcomes for TM; therefore, only TW meta-analysis results are reported. Fifty studies were identified having low-to-medium risk-of-bias scores. Among TW with HIV, 82% had ever received HIV care; 72% were receiving care, and 83% of those were retained in HIV care. Sixty-two percent were currently virally suppressed. Among those receiving HIV care or antiretroviral therapy (ART), 67% were virally suppressed at last test. Sixty-five percent were linked to HIV care 3 months or less after diagnosis. Seventy-one percent had ever been prescribed ART. Approximately 66% were taking ART, and 66% were ART-adherent. Only 56% were currently adherent the previous year. CONCLUSIONS: HIV care outcomes for TW were not ideal, and research gaps exists for TM. High heterogeneity was observed; therefore, caution should be taken interpreting the findings. Integrating transgender-specific health needs are needed to improve outcomes of transgender persons across the HIV care continuum.

Sociodemographic Characteristics of HIV Pre-Exposure Prophylaxis Use and Reasons for Nonuse Among Gay, Bisexual, and Other Men Who Have Sex with Men from Three US Cities.

HIV pre-exposure prophylaxis (PrEP) is a preventive medication that could reduce new infections among men who have sex with men (MSM). There are limited data on differing reasons for PrEP nonuse by condomless anal sex (CAS). We examined demographic and behavioral variables associated with PrEP use and reasons for PrEP nonuse by CAS. Data are from the M-cubed Study, collected in a 2018 baseline assessment of MSM (n = 798) in Atlanta, Detroit, and New York City. Participants reported current PrEP use (31%), previous use (8%), and never use (61%). MSM reporting CAS [adjusted odds ratio (aOR) = 2.60, confidence interval (95% CI) = 1.73-3.91], age 18-29 (aOR = 2.11, 95% CI = 1.26-3.52), 30-39 (aOR = 2.12, 95% CI = 1.25-3.59), with a college degree (aOR = 1.96, 95% CI = 1.20-3.21), or postgraduate education (aOR = 2.58, 95% CI = 1.51-4.40) had greater odds of current (vs. never) use; uninsured (aOR = 0.30, 95% CI = 0.16-0.57) men had lower odds of current (vs. never) use. For never use, more MSM who reported CAS (vs. did not) endorsed the following reasons (p's < 0.05): Insurance wouldn't cover PrEP (20% vs. 12%), Didn't know where to get it (33% vs. 24%) and fewer reported Didn't need PrEP (23% vs. 39%) and Started a committed relationship (7% vs. 25%). For discontinuation, more MSM who reported CAS (vs. did not) endorsed Worry about the safety of PrEP (19% vs. 3%). Efforts are needed to enhance PrEP as an option among older, less educated, and uninsured MSM. These findings may inform how providers can facilitate PrEP use by messaging on access and safety for MSM who reported CAS.

Preference for using a variety of future HIV pre-exposure prophylaxis products among men who have sex with men in three US cities.

BACKGROUND: Daily oral pre-exposure prophylaxis (PrEP) is available and recommended for men who have sex with men (MSM) at risk for HIV infection. Other HIV prevention products are being developed, including long-acting injectable (LAI) and event-based oral and topical formulations. Understanding preferences for potential products by MSM can help direct further development of prevention messaging. METHODS: We present baseline data from HIV-negative participants enrolled in the US Mobile Messaging for Men (M-cubed) Study. Participants were asked their likelihood of and rank order preference for using daily oral PrEP and various potential prevention products (one- to -three-month injections, 2-1-1 sexual event oral dosing, anal or penile gel, or anal suppository), and their sociodemographic characteristics. Bivariate and multivariable logistics regression assessed demographic associations with likelihood of use and rank order preference. RESULTS: Overall, most MSM reported a likelihood of using LAI (74%), sexual event-based pills (67%) and penile gel (64%). Men who reported recent unprotected (condomless and PrEPless) anal sex most preferred a penile gel formulation (74%), followed closely by LAI and event-based pills (73% each). Current PrEP users (vs. non-users) had greater odds of reporting likelihood to use LAI (AOR = 3.29, 95% CI = 2.12 to 5.11), whereas men reporting recent unprotected anal sex had a greater odds of likelihood to use a penile gel (AOR = 1.79, 95% CI = 1.27 to 2.52) and an anal suppository (AOR = 1.48, 95% CI = 1.08 to 2.02). Hispanic/Latino (vs. White) MSM (AOR = 2.29, 95% CI = 1.40 to 3.73) and, marginally, Black MSM (AOR = 1.54, 95% CI = 1.00 to 2.38) had greater odds of reporting likelihood to use penile gel. Similar patterns were found for rank ordering preference of products, including condoms. CONCLUSIONS: Most MSM were interested in using various potential future HIV prevention products, especially LAI. However, two typologies of potential users emerged: men who prefer sexual event-based methods (condoms, event-based pill, sexual gels and suppositories) and men who prefer non-sexual event-based methods (daily pill, LAI). Men who reported recent unprotected anal sex preferred a penile gel product most, followed closely by sexual event-based pills and LAI. Racial/ethnic differences were noted as well. These findings on product preferences can help in formulation development and messaging.

Psychosocial mediators of perceived stigma and suicidal ideation among transgender women.

BACKGROUND: Transgender women (TGW) in the U.S. experience high rates of stigma, depression, and elevated rates of suicide. This study examined correlates of suicidal ideation and estimated the conditional indirect effects of perceived stigma and psychosocial mediators on suicidal ideation. METHODS: Using a cross-sectional study design, TGW (N = 92) were recruited through snowball sampling in Atlanta, Georgia. Structured interviews were conducted. Suicidal ideation was assessed by combining two variables that measured suicidal thoughts. Logistic regression models were performed to identify the potential risk and protective factors for suicidal ideation. We examined hypothesized psychosocial factors, including anxiety, depression, psychosocial impact of gender minority status, and substance use behaviors as potential mediators for the relationship between perceived stigma and suicidal ideation. All models were controlled for age, race, education, and homelessness. RESULTS: Suicidal ideation was reported by 33% (N = 30) of the study participants. In multivariable analysis, suicidal ideation was associated with sexual abuse (AOR = 3.17, 95% CI = 1.10-9.30), anxiety (AOR = 1.74, 95% CI = 1.10-2.73), family verbal abuse (AOR = 2.99, 95% CI = 1.10-8.40), stranger verbal abuse (AOR = 3.21, 95% CI = 1.02-10.08), and psychosocial impact of gender minority status (AOR = 3.42, 95% CI = 1.81-6.46). Partner support was found to be the protective factor for suicidal ideation (AOR = 0.34, 95% CI = 0.13-0.90). In the mediation analysis, the psychosocial impact of gender minority status mediated the relationship between perceived stigma and suicidal ideation. The estimated conditional indirect effect was 0.46, (95% CI = 0.12-1.11). CONCLUSION: Interventions that aim to reduce suicidal behaviors among TGW should address stigma, psychosocial impact of gender minority status, and different forms of violence and abuse.

A comparative study of recombinant mouse and human apurinic/apyrimidinic endonuclease.

Mammalian apurinic/apyrimidinic endonuclease (APE1) initiates the repair of abasic sites (AP-sites), which are highly toxic, mutagenic, and implicated in carcinogenesis. Also, reducing the activity of APE1 protein in cancer cells and tumors sensitizes mammalian tumor cells to a variety of laboratory and clinical chemotherapeutic agents. In general, mouse models are used in studies of basic mechanisms of carcinogenesis, as well as pre-clinical studies before transitioning into humans. Human APE1 (hAPE1) has previously been cloned, expressed, and extensively characterized. However, the knowledge regarding the characterization of mouse APE1 (mAPE1) is very limited. Here we have expressed and purified full-length hAPE1 and mAPE1 in and from E. coli to near homogeneity. mAPE1 showed comparable fast reaction kinetics to its human counterpart. Steady-state enzyme kinetics showed an apparent K(m) of 91 nM and k(cat) of 4.2 s(-1) of mAPE1 for the THF cleavage reaction. For hAPE1 apparent K(m) and k(cat) were 82 nM and 3.2 s(-1), respectively, under similar reaction conditions. However, k(cat)/K(m) were in similar range for both APE1s. The optimum pH was in the range of 7.5-8 for both APE1s and had an optimal activity at 50-100 mM KCl, and they showed Mg(2+) dependence and abrogation of activity at high salt. Circular dichroism spectroscopy revealed that increasing the Mg(2+) concentration altered the ratio of "turns" to "ß-strands" for both proteins, and this change may be associated with the conformational changes required to achieve an active state. Overall, compared to hAPE1, mAPE1 has higher K(m) and k(cat) values. However, overall results from this study suggest that human and mouse APE1s have mostly similar biochemical and biophysical properties. Thus, the conclusions of mouse studies to elucidate APE1 biology and its role in carcinogenesis may be extrapolated to apply to human biology. This includes the development and validation of effective APE1 inhibitors as chemosensitizers in clinical studies.

A unified method for purification of basic proteins.

Protein purification is still very empirical, and a unified method for purifying proteins without an affinity tag is not available yet. In the postgenomic era, functional genomics, however, strongly demands such a method. In this paper we have formulated a unique method that can be applied for purifying any recombinant basic protein from Escherichia coli. Here, we have found that if the pH of the buffer is merely one pH unit below the isoelectric point (pI) of the recombinant proteins, most of the latter bind to the column. This result supports the Henderson-Hasselbalch principle. Considering that E. coli proteins are mostly acidic, and based on the pI determined theoretically, apparently all recombinant basic proteins (at least pI-1 > or = 6.94) may be purified from E. coli in a single step using a cation-exchanger resin, SP-Sepharose, and a selected buffer pH, depending on the pI of the recombinant protein. Approximately, two-fifths of human proteome, including many if not all nucleic acid-interacting proteins, have a pI of 7.94 or higher; virtually all these 12,000 proteins may be purified using this method in a single step.