The development, implementation and early learnings of a training program to advance interest in behavioral research careers among undergraduate BIPOC students majoring in psychology.

OBJECTIVES: Black, indigenous and people of color (BIPOC) remain underrepresented in research occupations. This report discusses a collaboration to train undergraduate BIPOC students in clinical research between a public health institute, two medical schools, and a historically Black College or University (HBCU). This nine-month program trained BIPOC undergraduates in research methodology, psychology, and addiction science, and immersed trainees in real-world research. The program included didactic seminars, experiential activities, and a mentored research project culminating in a poster and oral presentation. METHODS: Key learnings, program satisfaction survey results, and preliminary outcomes from the first three program cohorts (N = 6 students) are presented. This program addressed several barriers hypothesized to contribute to the limited number of BIPOC students pursuing research careers, including mentorship from BIPOC faculty and financial concerns. RESULTS: Students reported moderate to high satisfaction with the program and endorsed gaining new research skills. Limitations and future directions are discussed. CONCLUSION: The expansion of the BIPOC health and research workforce is an urgent priority given the importance of BIPOC professionals to the health of our nation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04650386.

Nurse home visiting to improve child and maternal outcomes: 5-year follow-up of an Australian randomised controlled trial.

OBJECTIVES: Nurse home visiting (NHV) is widely implemented to address inequities in child and maternal health. However, few studies have examined longer-term effectiveness or delivery within universal healthcare systems. We evaluated the benefits of an Australian NHV program ("right@home") in promoting children's language and learning, general and mental health, maternal mental health and wellbeing, parenting and family relationships, at child ages 4 and 5 years. SETTING AND PARTICIPANTS: Randomised controlled trial of NHV delivered via universal, child and family health services (the comparator). Pregnant women experiencing adversity (≥2 of 10 risk factors) were recruited from 10 antenatal clinics across 2 states (Victoria, Tasmania) in Australia. INTERVENTION: Mothers in the intervention arm were offered 25 nurse home visits (mean 23·2 home visits [SD 7·4, range 1-43] received) of 60-90 minutes, commencing antenatally and continuing until children's second birthdays. PRIMARY AND SECONDARY OUTCOMES MEASURED: At 4 and 5 years, outcomes were assessed via parent interview and direct assessment of children's language and learning (receptive and expressive language, phonological awareness, attention, and executive function). Outcomes were compared between intervention and usual care arms (intention to treat) using adjusted regression with robust estimation to account for nurse/site. Missing data were addressed using multiple imputation and inverse probability weighting. RESULTS: Of 722 women enrolled in the trial, 225 of 363 (62%) intervention and 201 of 359 (56%) usual care women provided data at 5 years. Estimated group differences showed an overall pattern favouring the intervention. Statistical evidence of benefits was found across child and maternal mental health and wellbeing, parenting and family relationships with effect sizes ranging 0·01-0·27. CONCLUSION: An Australian NHV program promoted longer-term family functioning and wellbeing for women experiencing adversity. NHV can offer an important component of a proportionate universal system that delivers support and intervention relative to need. TRIAL REGISTRATION: 2013-2016, registration ISRCTN89962120.

The Impact of Nurse Home Visiting on the Use, Dose and Quality of Formal Childcare: 3-Year Follow-Up of a Randomized Trial.

OBJECTIVE: We investigated whether nurse home visiting (NHV) affects the uptake and quality of formal early childhood education and care (ECEC) at child ages 2 and 3 years, and reasons for using ECEC at 3 years. METHODS: Design: Secondary analysis of the "right@home" randomized trial of NHV. PARTICIPANTS: 722 pregnant Australian, English-speaking women experiencing adversity recruited from antenatal clinics across 2 states. INTERVENTION: 25 nurse home visits to 2 years; Control: universal well-child nursing service. MEASURES: Parents reported formal ECEC use (government approved and subsidized), comprising long or family day care (LDC), and reasons for use. ECEC quality was classified using the Australian government's national ratings. Eighty-three percent of parents provided data at 2 years (306 intervention/290 control); and 69% at 3 years (255 intervention/240 control). ANALYSIS: Intention-to-treat analyses were conducted using adjusted regression models, addressing missing data using multiple imputation and inverse probability weighting. RESULTS: There was no evidence of group differences in ECEC uptake or quality, although control families may have used more LDC at 3 years (mean difference 2.8 hours, 95% confidence interval, -0.2 to 5.8 hours). Intervention parents reported using ECEC to support their children's social development more frequently than controls (48% vs 33%) but less for work/study (39% vs 46%). CONCLUSIONS: The right@home NHV program did not impact ECEC uptake or quality, although it may influence parents' reasons for using ECEC. If supported by policy and provision, there is an opportunity for NHV programs to promote the transition to high-quality ECEC and evaluate the synergistic benefit on children's development.

Economic evaluation of an Australian nurse home visiting programme: a randomised trial at 3 years.

OBJECTIVES: To investigate the additional programme cost and cost-effectiveness of 'right@home' Nurse Home Visiting (NHV) programme in relation to improving maternal and child outcomes at child age 3 years compared with usual care. DESIGN: A cost-utility analysis from a government-as-payer perspective alongside a randomised trial of NHV over 3-year period. Costs and quality-adjusted life-years (QALYs) were discounted at 5%. Analysis used an intention-to-treat approach with multiple imputation. SETTING: The right@home was implemented from 2013 in Victoria and Tasmania states of Australia, as a primary care service for pregnant women, delivered until child age 2 years. PARTICIPANTS: 722 pregnant Australian women experiencing adversity received NHV (n=363) or usual care (clinic visits) (n=359). PRIMARY AND SECONDARY OUTCOME MEASURES: First, a cost-consequences analysis to compare the additional costs of NHV over usual care, accounting for any reduced costs of service use, and impacts on all maternal and child outcomes assessed at 3 years. Second, cost-utility analysis from a government-as-payer perspective compared additional costs to maternal QALYs to express cost-effectiveness in terms of additional cost per additional QALY gained. RESULTS: When compared with usual care at child age 3 years, the right@home intervention cost $A7685 extra per woman (95% CI $A7006 to $A8364) and generated 0.01 more QALYs (95% CI -0.01 to 0.02). The probability of right@home being cost-effective by child age 3 years is less than 20%, at a willingness-to-pay threshold of $A50 000 per QALY. CONCLUSIONS: Benefits of NHV to parenting at 2 years and maternal health and well-being at 3 years translate into marginal maternal QALY gains. Like previous cost-effectiveness results for NHV programmes, right@home is not cost-effective at 3 years. Given the relatively high up-front costs of NHV, long-term follow-up is needed to assess the accrual of health and economic benefits over time. TRIAL REGISTRATION NUMBER: ISRCTN89962120.

Nurse Home Visiting and Maternal Mental Health: 3-Year Follow-Up of a Randomized Trial.

BACKGROUND: Poor mental health is recognized as one of the greatest global burdens of disease. Maternal mental health is crucial for the optimal health of mothers and their children. We examined the effects of an Australian Nurse Home Visiting (NHV) program (right@home), offered to pregnant women experiencing adversity, on maternal mental health and well-being at child age 3 years. METHODS: A randomized controlled trial of NHV delivered via universal child and family health services (2013-2016). Pregnant women experiencing adversity (≥2 of 10 risk factors) were recruited from 10 antenatal clinics across 2 states. Intervention comprised 25 home visits until child age 2 years. The outcomes assessed 1-year postintervention completion were maternal self-report of mental health symptoms (Depression Anxiety Stress Scales) and positive aspects of mental health (personal well-being and self-efficacy). RESULTS: Of the 722 women enrolled in the trial, 255 of 363 (70%) intervention and 240 of 359 (67%) control group women provided data at 3 years. Compared with controls, the intervention group reported better mental health (reverse Depression Anxiety Stress Scales scores): effect sizes of 0.25 (depression; 95% confidence interval [CI]: 0.08 to 0.32), 0.20 (anxiety; 95% CI: 0.05 to 0.30), 0.17 (stress; 95% CI: 0.09 to 0.37), and 0.23 (total score; 95% CI: 0.12 to 0.38); 0.16 (95% CI: 0.04 to 0.29) for personal well-being; and an odds ratio of 1.60 (95% CI: 1.19 to 2.16) for self-efficacy. CONCLUSIONS: An NHV designed to support mothers experiencing adversity can lead to later maternal mental health benefits, even after the program ends.

The Influence of Gender and Underrepresented Minority Status on Medical Student Ranking of Residency Programs.

BACKGROUND: Physician diversity is linked to improved quality of care of diverse patient populations. The transition from medical school to residency is an opportunity to improve and increase workforce diversity in all specialties. However, there is limited published literature on the factors contributing to the ranking of residency programs on women and underrepresented minorities (URMs). OBJECTIVE: To characterize factors medical students used to rank residency programs and describe any differences based on race/ethnicity or gender. METHODS: A mixed-methods study consisting of a web-based survey and semi-structured interviews with National Resident Matching Program (NRMP) participating graduates over a two-year period. The survey assessed demographics and a 6-point Likert scale rating of various factors used to rank residency programs. Unpaired student t-tests were used to compare means. A subset of students was interviewed and a modified grounded theory approach identified decision-making themes as well as the role of gender and URM status. RESULTS: Out of a total of 316 invitations sent, 148 completed the survey (46.8% response rate), of which 21% of respondents self-identified as URMs. The majority of respondents graduated in 2014 (53%), and were male (51%). Participants ranked program atmosphere, reputation, location, and proximity to family the highest. URM students ranked patient population (p < 0.01), revisit opportunities (p = 0.04), gender diversity (p < 0.01), and ethnic diversity (p < 0.01) significantly higher than non-URM students. Female students ranked patient population (p < 0.01) and gender diversity (p < 0.01) significantly higher than males. Qualitative findings revealed differences in perceptions by URMs and non-URMs of patient population, revisit opportunities, gender diversity, and ethnic diversity. CONCLUSIONS: While all students prioritized pragmatic factors, women and URM students assess and weigh additional factors related to culture, inclusion, and diversity more than others. By tailoring recruitment strategies to meet the expectations of women and URMs, residency programs can better meet goals in becoming more diverse and inclusive.

Measuring Organizational Cultural Competence to Promote Diversity in Academic Healthcare Organizations.

Purpose: To evaluate what drives respondent perceptions of health system organizational cultural competence. Methods: We estimated associations between survey respondent (n=3506) demographic characteristics, length of employment, position, and place of work and their reported perceptions of institutional culture. Results: In adjusted analyses, respondents self-identifying as non-Hispanic black versus non-Hispanic whites, females versus males, and lesbian/gay/bisexual/transgender/queer versus heterosexuals were significantly less likely to rank the cultural competence of their organization above average. Conclusion: Minorities and women were less likely to rank their organization as culturally competent. Organizational efforts to achieve cultural competency would benefit from measuring this factor to target their efforts.

Utilizing Remote Real-Time Videoconferencing to Expand Access to Cancer Genetic Services in Community Practices: A Multicenter Feasibility Study.

BACKGROUND: Videoconferencing has been used to expand medical services to low-access populations and could increase access to genetic services at community sites where in-person visits with genetic providers are not available. OBJECTIVE: To evaluate the feasibility of, patient feedback of, and cognitive and affective responses to remote two-way videoconferencing (RVC) telegenetic services at multiple sociodemographically diverse community practices without access to genetic providers. METHODS: Patients at 3 community sites in 2 US states outside the host center completed RVC pretest (visit 1, V1) and post-test (visit 2, V2) genetic counseling for cancer susceptibility. Surveys evaluated patient experiences, knowledge, satisfaction with telegenetic and cancer genetics services, anxiety, depression, and cancer worry. RESULTS: A total of 82 out of 100 (82.0%) approached patients consented to RVC services. A total of 61 out of 82 patients (74%) completed pretest counseling and 41 out of 61 (67%) proceeded with testing and post-test counseling. A total of 4 out of 41 (10%) mutation carriers were identified: BRCA2, MSH2, and PMS2. Patients reported many advantages (eg, lower travel burden and convenience) and few disadvantages to RVC telegenetic services. Most patients reported feeling comfortable with the video camera--post-V1: 52/57 (91%); post-V2: 39/41 (95%)--and that their privacy was respected--post-V1: 56/57 (98%); post-V2: 40/41 (98%); however, some reported concerns that RVC might increase the risk of a confidentiality breach of their health information--post-V1: 14/57 (25%); post-V2: 12/41 (29%). While the majority of patients reported having no trouble seeing or hearing the genetic counselor--post-V1: 47/57 (82%); post-V2: 39/41 (95%)--51 out of 98 (52%) patients reported technical difficulties. Nonetheless, all patients reported being satisfied with genetic services. Compared to baseline, knowledge increased significantly after pretest counseling (+1.11 mean score, P=.005); satisfaction with telegenetic (+1.74 mean score, P=.02) and genetic services (+2.22 mean score, P=.001) increased after post-test counseling. General anxiety and depression decreased after pretest (-0.97 mean anxiety score, P=.003; -0.37 mean depression score, P=.046) and post-test counseling (-1.13 mean anxiety score, P=.003; -0.75 mean depression score, P=.01); state anxiety and cancer-specific worry did not significantly increase. CONCLUSIONS: Remote videoconferencing telegenetic services are feasible, identify genetic carriers in community practices, and are associated with high patient satisfaction and favorable cognitive and affective outcomes, suggesting an innovative delivery model for further study to improve access to genetic providers and services. Potential barriers to dissemination include technology costs, unclear billing and reimbursement, and state requirements for provider licensure.

Patient feedback and early outcome data with a novel tiered-binned model for multiplex breast cancer susceptibility testing.

PURPOSE: The risks, benefits, and utilities of multiplex panels for breast cancer susceptibility are unknown, and new counseling and informed consent models are needed. We sought to obtain patient feedback and early outcome data with a novel tiered-binned model for multiplex testing. METHODS: BRCA1/2-negative and untested patients completed pre- and posttest counseling and surveys evaluating testing experiences and cognitive and affective responses to multiplex testing. RESULTS: Of 73 patients, 49 (67%) completed pretest counseling. BRCA1/2-negative patients were more likely to proceed with multiplex testing (86%) than those untested for BRCA1/2 (43%; P < 0.01). Many patients declining testing reported concern for uncertainty and distress. Most patients would not change anything about their pre- (76%) or posttest (89%) counseling sessions. Thirty-three patients (72%) were classified as making an informed choice, including 81% of those who proceeded with multiplex testing. Knowledge increased significantly. Anxiety, depression, uncertainty, and cancer worry did not significantly increase with multiplex testing. CONCLUSION: Some patients, particularly those without prior BRCA1/2 testing, decline multiplex testing. Most patients who proceeded with testing did not experience negative psychological responses, but larger studies are needed. The tiered-binned approach is an innovative genetic counseling and informed consent model for further study in the era of multiplex testing.Genet Med 18 1, 25-33.

Human subjects protection: an event monitoring committee for research studies of girls from breast cancer families.

PURPOSE: Researchers must monitor the safety of research participants, particularly in studies involving children and adolescents. Yet, there is limited guidance for the development and implementation of oversight committees for psychosocial, behavioral intervention, and observational studies. METHODS: We implemented a model for an Event Monitoring Committee (EMC) in three related studies recruiting 6- to 19-year-old girls from families with and without breast cancer. RESULTS: The EMC model can be valuable for investigators and local institutional review boards when additional oversight is desired. Recommendations are provided and intended to be broadly applicable to a wide range of research activities designed to improve the health of children, adolescents, and families. EMC goals, membership, and procedures for monitoring and assessing risks and benefits should be defined but should also be flexible and tailored to the study design and population. The EMC model also provides an independent comprehensive, study-wide oversight mechanism for multicenter psychosocial, behavioral intervention, and observational studies. CONCLUSIONS: An EMC provides an alternative oversight approach where additional independent assessment and oversight of study-related risks are desired, particularly in the setting of vulnerable populations, children and adolescents, or where risks nontraditional to the medical field (i.e., social, emotional, or cultural) are possible.

Stakeholders' opinions on the implementation of pediatric whole exome sequencing: implications for informed consent.

Advances in whole genome and whole exome sequencing (WGS/WES) technologies have led to increased availability in clinical settings. Currently, there are few guidelines relating to the process and content of informed consent for WGS/WES, nor to which results should be returned to families. To address this gap, we conducted focus groups to assess the views of professionals, parents, and adolescents for the future implementation of WES. The discussions assessed understanding of the risks and benefits of WES, preferences for the informed consent discussion, process for return of results, and the decision-making role of the pediatric patient. Professional focus group participants included bioethicists, physicians, laboratory directors, and genetic counselors. Parent focus groups included individuals with children who could be offered sequencing due to a potential genetic cause of the child's condition. On-line discussion groups were conducted with adolescents aged 13-17 who had a possible genetic disorder. We identified discrepancies between professionals and patient groups regarding the process and content of informed consent, preference for return of results, and the role of the child in decision-making. Professional groups were concerned with the uncertainty regarding professional obligations, changing interpretation in genomic medicine, and practical concerns of returning results over time. Parent and adolescent groups focused on patient choice and personal utility of sequencing results. Each group expressed different views on the role of the child in decision-making and return of results. These discrepancies represent potential barriers to informed consent and a challenge for genetic counselors regarding the involvement of pediatric patients in decision-making and return of results discussions.

Measuring children's decision-making involvement regarding chronic illness management.

OBJECTIVES: To develop a measure of decision-making involvement in children and adolescents with cystic fibrosis, diabetes, and asthma. METHODS: Parent-child dyads completed the Decision-Making Involvement Scale (DMIS) and measures of locus of control and family communication. DMIS items were subjected to exploratory and confirmatory factor analysis (CFA). Temporal stability and construct validity were assessed. RESULTS: The parent form was reduced to 20 items representing five factors. CFA showed that the five factors were an acceptable fit to the parent- and child-report data. Internal consistency values ranged from 0.71 to 0.91. Temporal stability was supported by moderate-substantial intraclass correlation coefficients. DMIS subscales were associated with child age, child locus of control, and family communication. CONCLUSIONS: The DMIS can be used to inform our understanding of the transition to greater independence for illness management. Additional research is needed to examine outcomes of decision-making involvement, including treatment adherence and responsibility.

The decision making control instrument to assess voluntary consent.

BACKGROUND: The decision to participate in a research intervention or to undergo medical treatment should be both informed and voluntary. OBJECTIVE: The aim of the present study was to develop an instrument to measure the perceived voluntariness of parents making decisions for their seriously ill children. METHODS: A total of 219 parents completed questionnaires within 10 days of making such a decision at a large, urban tertiary care hospital for children. Parents were presented with an experimental form of the Decision Making Control Instrument (DMCI), a measure of the perception of voluntariness. Data obtained from the 28-item form were analyzed using a combination of both exploratory and confirmatory factor analytic techniques. RESULTS: The 28 items were reduced to 9 items representing 3 oblique dimensions: Self-Control, Absence of Control, and Others' Control. The hypothesis that the 3-factor covariance structure of our model was consistent with that of the data was supported. Internal consistency for the scale as a whole was high (0.83); internal consistency for the subscales ranged from 0.68 to 0.87. DMCI scores were associated with measures of affect, trust, and decision self-efficacy, supporting the construct validity of the new instrument. CONCLUSION: The DMCI is an important new tool that can be used to inform our understanding of the voluntariness of treatment and research decisions in medical settings.

Engineering of Penicillium chrysogenum for fermentative production of a novel carbamoylated cephem antibiotic precursor.

Penicillium chrysogenum was successfully engineered to produce a novel carbamoylated cephalosporin that can be used as a synthon for semi-synthetic cephalosporins. To this end, genes for Acremonium chrysogenum expandase/hydroxylase and Streptomyces clavuligerus carbamoyltransferase were expressed in a penicillinG high-producing strain of P.chrysogenum. Growth of the engineered strain in the presence of adipic acid resulted in production of adipoyl-7-amino-3-carbamoyloxymethyl-3-cephem-4-carboxylic acid (ad7-ACCCA) and of several adipoylated pathway intermediates. A combinatorial chemostat-based transcriptome study, in which the ad7-ACCCA-producing strain and a strain lacking key genes in beta-lactam synthesis were grown in the presence and absence of adipic acid, enabled the dissection of transcriptional responses to adipic acid per se and to ad7-ACCCA production. Transcriptome analysis revealed that adipate catabolism in P.chrysogenum occurs via beta-oxidation and enabled the identification of putative genes for enzymes involved in mitochondrial and peroxisomal beta-oxidation pathways. Several of the genes that showed a specifically altered transcript level in ad7-ACCCA-producing cultures were previously implicated in oxidative stress responses.

Exploring and dissecting genome-wide gene expression responses of Penicillium chrysogenum to phenylacetic acid consumption and penicillinG production.

BACKGROUND: Since the discovery of the antibacterial activity of penicillin by Fleming 80 years ago, improvements of penicillin titer were essentially achieved by classical strain improvement through mutagenesis and screening. The recent sequencing of Penicillium chrysogenum strain Wisconsin1255-54 and the availability of genomics tools such as DNA-microarray offer new perspective. RESULTS: In studies on beta-lactam production by P. chrysogenum, addition and omission of a side-chain precursor is commonly used to generate producing and non-producing scenarios. To dissect effects of penicillinG production and of its side-chain precursor phenylacetic acid (PAA), a derivative of a penicillinG high-producing strain without a functional penicillin-biosynthesis gene cluster was constructed. In glucose-limited chemostat cultures of the high-producing and cluster-free strains, PAA addition caused a small reduction of the biomass yield, consistent with PAA acting as a weak-organic-acid uncoupler. Microarray-based analysis on chemostat cultures of the high-producing and cluster-free strains, grown in the presence and absence of PAA, showed that: (i) Absence of a penicillin gene cluster resulted in transcriptional upregulation of a gene cluster putatively involved in production of the secondary metabolite aristolochene and its derivatives, (ii) The homogentisate pathway for PAA catabolism is strongly transcriptionally upregulated in PAA-supplemented cultures (iii) Several genes involved in nitrogen and sulfur metabolism were transcriptionally upregulated under penicillinG producing conditions only, suggesting a drain of amino-acid precursor pools. Furthermore, the number of candidate genes for penicillin transporters was strongly reduced, thus enabling a focusing of functional analysis studies. CONCLUSION: This study demonstrates the usefulness of combinatorial transcriptome analysis in chemostat cultures to dissect effects of biological and process parameters on gene expression regulation. This study provides for the first time clear-cut target genes for metabolic engineering, beyond the three genes of the beta-lactam pathway.

Genome sequencing and analysis of the filamentous fungus Penicillium chrysogenum.

Industrial penicillin production with the filamentous fungus Penicillium chrysogenum is based on an unprecedented effort in microbial strain improvement. To gain more insight into penicillin synthesis, we sequenced the 32.19 Mb genome of P. chrysogenum Wisconsin54-1255 and identified numerous genes responsible for key steps in penicillin production. DNA microarrays were used to compare the transcriptomes of the sequenced strain and a penicillinG high-producing strain, grown in the presence and absence of the side-chain precursor phenylacetic acid. Transcription of genes involved in biosynthesis of valine, cysteine and alpha-aminoadipic acid-precursors for penicillin biosynthesis-as well as of genes encoding microbody proteins, was increased in the high-producing strain. Some gene products were shown to be directly controlling beta-lactam output. Many key cellular transport processes involving penicillins and intermediates remain to be characterized at the molecular level. Genes predicted to encode transporters were strongly overrepresented among the genes transcriptionally upregulated under conditions that stimulate penicillinG production, illustrating potential for future genomics-driven metabolic engineering.

Formate as an auxiliary substrate for glucose-limited cultivation of Penicillium chrysogenum: impact on penicillin G production and biomass yield.

Production of beta-lactams by the filamentous fungus Penicillium chrysogenum requires a substantial input of ATP. During glucose-limited growth, this ATP is derived from glucose dissimilation, which reduces the product yield on glucose. The present study has investigated whether penicillin G yields on glucose can be enhanced by cofeeding of an auxiliary substrate that acts as an energy source but not as a carbon substrate. As a model system, a high-producing industrial strain of P. chrysogenum was grown in chemostat cultures on mixed substrates containing different molar ratios of formate and glucose. Up to a formate-to-glucose ratio of 4.5 mol.mol(-1), an increasing rate of formate oxidation via a cytosolic NAD(+)-dependent formate dehydrogenase increasingly replaced the dissimilatory flow of glucose. This resulted in increased biomass yields on glucose. Since at these formate-to-glucose ratios the specific penicillin G production rate remained constant, the volumetric productivity increased. Metabolic modeling studies indicated that formate transport in P. chrysogenum does not require an input of free energy. At formate-to-glucose ratios above 4.5 mol.mol(-1), the residual formate concentrations in the cultures increased, probably due to kinetic constraints in the formate-oxidizing system. The accumulation of formate coincided with a loss of the coupling between formate oxidation and the production of biomass and penicillin G. These results demonstrate that, in principle, mixed-substrate feeding can be used to increase the yield on a carbon source of assimilatory products such as beta-lactams.

Acknowledging adult bias: a focus-group approach to utilizing beauty salons as health-education portals for inner-city adolescent girls.

To assess the feasibility of using beauticians as health literacy agents and beauty salons as health-education portals for adolescent, inner-city, African American girls, the authors conducted focus groups with 25 women: salon clients, salon owners, and medical students. Facilitators to program development included (a) beautician-client relationships, (b) teens' access to health information, and (c) beauticians as information resources. Barriers included (a) adult opinions of teen behaviors, (b) teen mistrust of adults, and (c) low health literacy of beauticians. In developing a health-education program for this population, beauticians and salons may be excellent health information agents and portals if barriers including beautician poor health literacy, adolescent mistrust in adults, and adults' anti-adolescent bias are improved. Program implementation must not solely focus on teens but should also include adult salon users, with the goal of reaching the teens first through these adults and, with time and trust, reaching the teens directly.

Enzymic analysis of NADPH metabolism in beta-lactam-producing Penicillium chrysogenum: presence of a mitochondrial NADPH dehydrogenase.

Based on assumed reaction network structures, NADPH availability has been proposed to be a key constraint in beta-lactam production by Penicillium chrysogenum. In this study, NADPH metabolism was investigated in glucose-limited chemostat cultures of an industrial P. chrysogenum strain. Enzyme assays confirmed the NADP(+)-specificity of the dehydrogenases of the pentose-phosphate pathway and the presence of NADP(+)-dependent isocitrate dehydrogenase. Pyruvate decarboxylase/NADP(+)-linked acetaldehyde dehydrogenase and NADP(+)-linked glyceraldehyde-3-phosphate dehydrogenase were not detected. Although the NADPH requirement of penicillin-G-producing chemostat cultures was calculated to be 1.4-1.6-fold higher than that of non-producing cultures, in vitro measured activities of the major NADPH-providing enzymes were the same. Isolated mitochondria showed high rates of antimycin A-sensitive respiration of NADPH, thus indicating the presence of a mitochondrial NADPH dehydrogenase that oxidises cytosolic NADPH. The presence of this enzyme in P. chrysogenum might have important implications for stoichiometric modelling of central carbon metabolism and beta-lactam production and may provide an interesting target for metabolic engineering.