Effectiveness and cost effectiveness of a stress management training for leaders of small and medium sized enterprises - study protocol for a randomized controlled-trial.

BACKGROUND: Leaders in small and medium-sized enterprises (SMEs) are exposed to increased stress as a result of a range of challenges. Moreover, they rarely have the opportunity to participate in stress management trainings. Therefore, KMU-GO (ger: Kleine und mittlere Unternehmen - Gesundheitsoffensive; en: small and medium-sized enterprises - health campaign) aims at conducting and evaluating such a stress management training. The focus of evaluation does not only lie on the effects on leaders participating but also on their employees. METHODS: The study is planned as a 2 × 3 mixed design with two groups (intervention and waiting control group) as a between factor and point in time (at baseline, 6 and 12 months later) as a within factor. We aim at collecting data from N = 200 leaders. Based on the results of a preceding assessment, an already successfully implemented stress management training was adapted to SME needs and now serves as the framework of this intervention. The stress management training comprises one and a half days and is followed by two booster sessions (each 180 min) about 3 and 6 months after the training. The main focus of this intervention lies on specifying leaders stress reactivity while at the same time investigating its effects on employees' mental health. Further dependent variables are leaders´ depression and anxiety scores, effort-reward imbalance, sick days and psychophysiological measures of heart rate variability, hair cortisol, and salivary alpha-amylase. Cost-effectiveness analyses will be conducted from a societal and employers' point of view. DISCUSSION: Stress management is a highly relevant issue for leaders in SMEs. By providing an adequate occupational stress management training, we expect to improve leaders´ and also employees` mental health, thereby preventing economic losses for SMEs and the national economy. However, collecting data from employees about the success of a stress management training of their leader is a highly sensitive topic. It requires a carefully planned proceeding ensuring for example a high degree of transparency, anonymity, and providing team incentives. TRIAL REGISTRATION: The KMU-GO trial is registered at the German Clinical Trial Register (DRKS): DRKS00023457 (05.11.2020).

Understanding the viral load during the synthesis and after rebinding of virus imprinted particles via real-time quantitative PCR.

In the present study, virus imprinted particles have been synthesized for recognizing and specifically binding viruses. These materials may be used for biomimetic sensing schemes and for selective removal of virus particles. Virus imprinting procedures require careful optimization of the synthesis route for obtaining selective and efficiently binding imprinted materials. A remaining limitation has been a facile method for the quantification of the viral load during the imprinting process. Herein, human adenovirus (AdV) was selected as a model virus facilitating the development and application of a rapid virus quantification method based on a molecular biological approach. A real-time quantitative polymerase chain reaction, a.k.a., the qPCR method was developed for monitoring the AdV viral load during the synthesis of AdV imprinted particles, and subsequent rebinding studies. The developed analytical strategy allows the direct, rapid, and sensitive quantification of human adenovirus type 5 concentrations during synthesis and application of AdV imprinted polymers (AdV-MIPs) with a broad dynamic range suitable for both application scenarios. In addition, it was demonstrated by gel electrophoresis analysis that viruses indeed bind to the beads even after several washing steps.

Hormone therapy in menopausal women with cognitive complaints: a randomized, double-blind trial.

OBJECTIVE: To evaluate the effects of hormone therapy (HT) on cognition and subjective quality of life (QoL) in recently postmenopausal women with cognitive complaints. METHODS: Cognitive Complaints in Early Menopause Trial (COGENT) was a randomized, double-blind, placebo-controlled, multicenter, pilot study of 180 healthy postmenopausal women aged 45 to 55 years, randomly assigned to receive either placebo or conjugated equine estrogen 0.625 mg/medroxyprogesterone acetate 2.5 mg for 4 months. Outcome measures included memory, subjective cognition, QoL, sexuality, and sleep, which were assessed at baseline and month 4. RESULTS: The study was terminated before the expected final sample size of 275 due to a decrease in enrollment coinciding with the publication of findings from the Women's Health Initiative. There were no differences between groups on any cognitive or QoL measures, except for an increase in sexual interest and thoughts with HT. Modest negative effects on short- and long-term verbal memory approached significance (p < 0.10). Women with baseline vasomotor symptoms (VMS) showed a decrease in VMS and an improvement in general QoL, but no cognitive benefit vs placebo. CONCLUSIONS: With the power to detect an effect size of >or=0.45, this study suggests potential modest negative effects on verbal memory that are consistent with previous hormone therapy trials in older women.

SELDI-TOF MS serum protein profiles in breast cancer: assessment of robustness and validity.

There is an urgent need for new serum markers that can be applied in e.g. the early detection of breast cancer. Following detection of new, potential biomarkers, such as those reported by Vlahou et al. (Clin Breast Cancer 2003;4:230-239) and Laronga et al. (Dis Markers 2003;19:229-238), assessment of both their robustness and validity is essential to confirm their clinical applicability. We therefore aimed to determine robustness and validity of biomarkers reported by the authors mentioned, by analysis of an independent sample set (breast cancer: n=47, normal women: n=45) in our laboratory, according to the methods described by both authors. Although all markers for the differentiation between breast cancer patients and normal women, discovered in the study of Vlahou et al., were recovered in our validation data set, none had sufficient performance to be applied as a classifier. The markers discovered by Laronga et al. in the differentiation between lymph node positive and -negative breast cancer patients were in part recovered from our validation data set, but were also not applicable as a classifier. In conclusion, although (part of) the proteins discovered and designated as markers by either author could be detected, their validity as biomarkers could not be confirmed by the current study. This finding stresses that, when reporting on a potential biomarker, confirmation of both robustness and validity is essential in obtaining its true clinical applicability.

Dithranol in a cream preparation: disperse or dissolve?

In the search for the ideal dithranol cream preparation for short-contact treatment of psoriasis, we investigated the clinical efficacy, side effects and patient appreciation of two dithranol cream preparations (cream A and B) in a double-blind left-right comparing study. Dithranol was dissolved at preparation in cream A and dispersed in cream B. Cream A is known to have a shelf life of 1 year, while cream B has a much shorter shelf life (several months). Ten patients with chronic plaque-type psoriasis were treated during 7 weeks in a short-contact regimen. The clinical efficacy was monitored by scoring of erythema, induration, scaling and involved area (PASI); skin irritation was scored visually, and patient appreciation was evaluated by means of a multiple-choice questionnaire. Dispersion of dithranol in a cream was associated with less irritation and less discoloration of the skin, and its efficacy was comparable with that of the cream in which the dithranol was dissolved. As the dispersed dithranol formulation is easier to be manufactured, its quality will be less depending on the pharmacist's experience and equipment, and so more reliable. Besides, it will be less expensive to prepare. We advise to use this formulation for short-contact treatment.

A multicenter randomized comparison of cycle control and laboratory findings with oral contraceptive agents containing 100 microg levonorgestrel with 20 microg ethinyl estradiol or triphasic norethindrone with ethinyl estradiol.

OBJECTIVE: This study was undertaken to compare the effects of 2 oral contraceptive regimens on menstrual cycle control and laboratory findings. METHODS: In a multicenter randomized study 100 microg levonorgestrel with 20 microg ethinyl estradiol (Alesse or Loette) was given to 155 healthy women. A triphasic preparation of 500, 750, and 1000 microg norethindrone with 35 microg ethinyl estradiol (Ortho-Novum 7/7/7 or TriNovum) was given to 167 women for 1 to 4 cycles of treatment. RESULTS: Overall, the percentages of normal menstrual cycles and the percentages of cycles with intermenstrual and withdrawal bleeding were similar between the 2 treatment groups. In the levonorgestrel with ethinyl estradiol group, there was a statistically significantly longer latent period and a statistically significantly shorter withdrawal bleeding episode. Adverse events were similar between treatment groups, and none were serious. Most mean changes from baseline laboratory values were comparable between groups, although the mean increase in cholesterol concentration was statistically significantly lower in the levonorgestrel with ethinyl estradiol group. Changes in triglyceride and glucose concentrations were not statistically significantly different between groups. CONCLUSIONS: Levonorgestrel (100 microg) with ethinyl estradiol (20 microg) provides menstrual cycle control equivalent to that obtained with triphasic norethindrone with ethinyl estradiol (75% higher estrogen dose) with similar safety and tolerability.

Regulation of creatine kinase isoenzymes in human placenta during early, mid-, and late gestation.

OBJECTIVE: Creatine kinase (CK) isoenzymes play an important role in cellular energy transduction. Two isoenzymes of creatine kinase, ubiquitous mitochondrial creatine kinase (uMtCK) and cytosolic brain creatine kinase (BCK), are postulated to form the creatine phosphate (CP) shuttle, in which creatine serves to transport high-energy phosphate from the mitochondria to its site of utilization. Coordinate regulation of these genes is essential for efficient energy transduction. We examined human CK isoenzyme regulation in placentas during all three trimesters of gestation to define the mRNA and protein expression patterns of uMtCK and BCK and to test the CP shuttle hypothesis. METHODS: Placental samples were collected from a total of 26 patients from the first, second, and third trimesters. Total RNA and protein were prepared from each sample and quantified. Quantitative RNA analysis was performed by gel electrophoresis and dot blot techniques using isoenzyme-specific human cDNA probes for uMtCK and BCK. Protein expression of uMtCK and BCK was examined by Western blot analysis using isoenzyme-specific antibodies to uMtCK and BCK. RESULTS: Analysis of RNA demonstrated the coordinate expression of uMtCK and BCK mRNAs in human placenta, with peak expression of both in the term placentas. Western blot analysis demonstrated coordinate expression of uMtCK and BCK proteins in the first and second trimesters, but not in the term placenta. Expression levels of uMtCK and BCK proteins were not consistent with their respective mRNA levels in the term placenta. CONCLUSION: Expression of uMtCK and BCK in human placenta is highly regulated, and post-transcriptional regulation of uMtCK and BCK expression occurs in the term placenta. The coordinate regulation of uMtCK and BCK in human placenta supports the CP shuttle hypothesis. This analysis demonstrates that human placenta has high energy needs that can change rapidly; thus, a functioning CP shuttle may be important in the maintenance and termination of pregnancy.

The evolution of new agents for ovulation induction.

The field of clinical ovulation-induction therapy has remained relatively static for over 30 years. This field promises to benefit from advances in our understanding of the biology of ovulation, and from exciting new work in the areas of molecular and cellular biology and in the biochemistry of steroids, gonadotropins, and their receptors. New therapies with recombinant gonadotropins and their analogues show promise for the near future. Advances in our ability to stimulate and suppress the reproductive axis through central mechanisms also show some promise. In the long term, our understanding of the mechanisms involved in folliculogenesis and oocyte maturation may be combined with an enhanced ability to dissect these processes that lead to disordered ovulation. Our improved understanding of the implantation process may well lead to an ability to create nearly universal nidation in women who are undergoing ART or who have implantation disorders. This article discusses some of the many new opportunities in the clinical and basic science of ovulation induction. New technologies, such as those available through the Human Genome Project, and the use of genetic manipulation of animal models will stimulate additional new avenues of research.

Endometrial thickness is a valid monitoring parameter in cycles of ovulation induction with menotropins alone.

OBJECTIVE: To evaluate the ability of an ultrasound (US)-measured periovulatory endometrial thickness to predict conception in hMG-stimulated cycles. DESIGN: Retrospective. SETTING: A university-based tertiary practice. PATIENTS: One hundred twelve patients undergoing 292 cycles of ovulation induction with hMG alone. MAIN OUTCOME MEASURES: A periovulatory transvaginal US measurement of endometrial thickness was obtained during cycles of ovulation induction with hMG alone. Clinical pregnancy was defined by fetal cardiac activity. Sensitivity and false-positive rates for multiple discriminatory values of endometrial thickness were calculated and a relative operating characteristic (ROC) curve was constructed to evaluate the performance of this test as a predictor of pregnancy. RESULTS: Thirty-eight of 292 cycles resulted in pregnancy. Conception and nonconception cycles showed similar demographics, diagnoses, peak E2, maximum number of follicles, midluteal P, and mean endometrial thickness. Ovulatory dysfunction was a more frequent diagnosis in the conception group. Relative operating characteristic analysis for endometrial thickness as a predictor of pregnancy yielded an area under the curve of 0.623 +/- 0.049 (mean +/- SD). CONCLUSION: Endometrial thickness is a valid screening test for conception outcome in cycles stimulated with hMG. A periovulatory endometrial thickness > or = 10 mm defined 91% of conception cycles. No pregnancy occurred when the endometrium measured < 7 mm.

Evolution of clinical agents for ovulation induction.

Since the first use of human urinary gonadotropins in the 1960s, the number of agents available for ovulation induction has remained fairly static. However, the nature of gonadotropin therapy is expected to change rapidly in the near future, and by the end of the decade these changes may be augmented by nongonadotropin ovulation induction therapies. Newer agents described in the literature include highly purified preparations of follicle-stimulating hormone and recombinant forms of follicle-stimulating hormone, luteinizing hormone, and human chorionic gonadotropin. Protein fragments, cytokines, and growth factors also show great promise as ovulation adjuncts. Other promising approaches being explored are the use of genetically engineered human gonadotropin derivatives, the creation of chimeric proteins, and gene therapy.

Does intrauterine insemination offer an advantage to cervical cap insemination in a donor insemination program?

OBJECTIVE: To compare pregnancy outcome after IUI versus cervical cap insemination in a donor insemination program. DESIGN: A randomized prospective clinical trial in which patients were alternately inseminated with cryopreserved human semen using either IUI or cervical cap insemination methods. SETTING: The donor insemination program at Washington University School of Medicine. PATIENTS: Forty-two women with either isolated male factor or male factor plus corrected ovulatory dysfunction using clomiphene citrate underwent 141 cycles of donor insemination. MAIN OUTCOME MEASURES: Clinical pregnancy rates (PRs) defined as a viable intrauterine gestation > 12 weeks or delivered were compared between groups using the chi 2 test. RESULTS: Clinical PRs were significantly higher in the IUI group (16.4%) compared with the cervical cap insemination group (5.9%). The spontaneous abortion rates were similar between the IUI (1.4%) and cervical cap insemination groups (4.4%). CONCLUSIONS: These findings suggest an advantage to IUI over cervical cap insemination in a donor insemination program.

Influence of amino acids of a carrier protein flanking an inserted T cell determinant on T cell stimulation.

CD4+ helper T cells recognize antigen in association with MHC class II molecules. To investigate the role of the context of a minimal T cell epitope on presentation and recognition in association with MHC class II molecules, an epitope of the 65 kDa heat shock protein of Mycobacterium tuberculosis was inserted at four different sites in the outer membrane protein PhoE of Escherichia coli. Only some of the constructs could stimulate the epitope-specific T cell clone A2b in vitro. One non-stimulatory construct could be made stimulatory by denaturation, suggesting that the protein conformation prevents correct presentation of the epitope. Other non-stimulatory constructs did not become stimulatory with denaturation. One of these constructs could be made stimulatory by substitution of either one of the two amino acids directly preceding the minimal epitope in the recombinant protein. In synthetic peptides the presence of these upstream residues did not interfere with T cell recognition, suggesting that these residues influence processing of the recombinant protein. Flanking amino acids also influenced induction of a T cell response against the inserted epitope in vivo. These results demonstrate that insertion of minimal T cell epitopes in carrier proteins for the design of vaccines might fail because of the inhibiting effects of flanking residues.

Expression of engineered human 17 beta-estradiol dehydrogenase in a prokaryotic system.

OBJECTIVE: 17 beta estradiol dehydrogenase (17 beta DH) is a model for pyridine-dependent steroid-converting enzymes. To define the structural and functional parameters of 17 beta DH, we created an expression system for production of abundant, homogeneous enzyme. METHODS: A full-length 17 beta DH cDNA clone was engineered into the inducible expression vector pMON 5839. After induction of plasmid-bearing Escherichia coli JM109 cells, the authenticity of the recombinant human placental 17 beta DH (r17 beta DH) was evaluated. RESULTS: Protein electrophoresis and Western blot analysis confirmed the immunologic identity of r17 beta DH with native human placental enzyme. The amino acid sequence, enzyme activity, Vmax, K(m), and kcat of r17 beta DH matched that of the native enzyme. CONCLUSION: Prokaryotic cell lines offer the opportunity to create an unlimited supply of recombinant human placental 17 beta DH without the expense and time commitment of baculoviral or eukaryotic cell lines. We are now able to use r17 beta DH and its mutants to elucidate the mechanisms of action of this class of enzyme.

Long-term follow-up of couples after hamster egg penetration testing.

OBJECTIVE: To determine the clinical usefulness of the zona-free hamster egg penetration test as a long-term prognostic indicator for future pregnancy. SETTING: Division of Reproductive Endocrinology and Infertility at the Washington University Medical Center. PARTICIPANTS: All couples (n = 148) who had a hamster egg penetration assay performed between March 1, 1985 and December 31, 1986 were identified and followed with direct or telephone contact up to 68 months after the initial assay. MAIN OUTCOME MEASURE: The monthly fecundity rates using life table analysis and the 5-year incidence of pregnancy were categorized by the percentage of hamster eggs penetrated and by history of previous urologic surgery. RESULTS: There were no significant differences in the rate nor incidence of pregnancy in couples with hamster egg penetration scores of 0%, > 0% and < or = 10%, > 10% and < or = 20%, or > 20%. Although men with previous urologic surgery tended to have lower scores, there was no significant difference in the 5-year incidence of pregnancy. CONCLUSION: The hamster egg penetration score is not predictive of incidence of pregnancy nor time to conception.

Pregnancy in a woman with a uterine septum. A case report.

A term pregnancy occurred in the presence of a significant uterine septum. The changes in the anatomic appearance of the septum were documented sonographically throughout the gestation. A complete workup for other causes of pregnancy loss and attention to obstetric detail are central to the management of such patients.

Therapeutic donor insemination: a prospective randomized study of scheduling methods.

OBJECTIVE: To compare basal body temperature (BBT) graphs and urinary luteinizing hormone (LH) monitoring in scheduling therapeutic donor insemination. DESIGN: Participants were prospectively randomized to the BBT or LH groups. SETTING: Participants were private patients of the Reproductive Endocrine Division at Washington University School of Medicine. PATIENTS: Inclusion criteria were designed to assure an isolated male factor. Seventy-four of 113 patients completed the study; 18 had ongoing treatment at the end of the study. INTERVENTIONS: Basal body temperature graphs were physician interpreted and appointments prospectively chosen. Luteinizing hormone patients monitored daily urine samples and scheduled an appointment the day after the detected surge. MAIN OUTCOME MEASURES: Fecundity rates, cumulative pregnancy rates, and cost per pregnancy were all prospectively evaluated. RESULTS: Life table analysis yielded a 6-month cumulative probability of pregnancy of 36.3% in the LH group and 65.1% in the BBT group (P less than 0.025). The total cost per pregnancy was lower in the BBT group (+6,212 versus +3,997; P less than 0.001). CONCLUSIONS: This randomized prospective study demonstrates significant therapeutic and economic advantages when therapeutic donor insemination is prospectively scheduled by BBT graphs.