Seroprevalence of toxoplasmosis and current thinking regarding screening in pregnancy: A review of the literature and case study discussion

The approach to the diagnosis and treatment of congenital toxoplasmosis has been one of flux and debate, fueled by lack of knowledge, lack of consensus, different methods of screening and different national policies for screening in different parts of the world. Countries with higher prevalence of disease such as in Europe and South America have a heightened awareness of the need to screen and treat for this parasitic infection during pregnancy. In contrast, in the United States, it is a condition scarcely discussed and has been largely ignored except in some large centers and by a few researchers. Policies and research strategies for any condition should start with obtaining good data. The aims of this thesis included a review of prevalence studies conducted in the United States, focused on the past 20 years, combined with a description of original research conducted by the author several years ago. The latter was a cross-sectional study performed in Houston, one of the largest American cities with a great ethnic mix. The study analyzed prevalence rates of Toxoplasma gondii IgG antibody in sera of women of reproductive age. Overall seroprevalence was 12.3%. In keeping with other studies, higher prevalence correlated with lower socioeconomic status, Black and Hispanic and Asian ethnicities, and increasing age. A literature search revealed only three prevalence studies performed in the United States over the past 20 years, with another four studies only referred to as personal communications or within a textbook, without further study detail available. The literature review also revealed a lack of consensus on whether or not to screen for toxoplasmosis in pregnancy, and even whether or not treatment in utero is worthwhile.^ Proponents of screening and treatment in pregnancy site studies both in the United States and France, emphasize that treatment reduces disease manifestations in infants. Opponents cite other studies that show only marginal benefits, together with potential side effects of medication regimens and generation of anxiety in parents. What is agreed on so far is the value of educating pregnant women on how to avoid contracting toxoplasmosis, and educating physicians on making the best use of reference laboratories before major treatment decisions are made. Further research to reevaluate the literature critically, review new treatment regimens and examine costs and benefits of screening and treatment of toxoplasmosis in pregnancy, bringing together European and American researchers, is needed.^

Using 'Generic Abilities' to Foster Professionalism in a Post-Professional Program

Introduction To be successful in a profession, persons must have mastery of professional affective behaviors in addition to that profession’s core knowledge base. Health care delivery is more than just developing a good plan of care. The effective health care provider also will have good interpersonal and communication skills, have a commitment to learning, act professionally and responsibly, and have abilities in problem solving and critical thinking. But, these behaviors and characteristics are not taught directly in a professional program. This presentation will demonstrate how these ‘generic abilities’ have been incorporated in a post-professional program and how they can be used in other professional health care, professional development, and leadership programs. [See PDF for complete abstract]

Convergent and divergent modulatory pathways in {\it Aplysia\/}: Cellular and network studies

Neuromodulation is essential to many functions of the nervous system. In the simple gastropod mollusk Aplysia californica, neuromodulation of the circuits for the defensive withdrawal reflexes has been associated with several forms of learning. In the present work, the neurotransmitters and neural circuitry which contribute to the modulation of the tail-siphon withdrawal reflex were examined.^ A recently-identified neuropeptide transmitter, buccalin A was found to modulate the biophysical properties of the sensory neurons that mediate the reflex. The actions of buccalin A on the sensory neurons were compared with those of the well-characterized modulatory transmitter serotonin, and convergence and divergence in the actions of these two transmitters were evaluated. Buccalin A dramatically increased the excitability of sensory neurons and occluded further enhancement of excitability by serotonin. Buccalin A produced no significant change in spike duration, and it did not block serotonin-induced spike broadening. Voltage-clamp analysis revealed the currents that may be involved in the effects on spike duration and excitability. Buccalin A decreased an outward current similar to the S-K$\sp+$ current (I$\sb{\rm K,S}$). Buccalin A appeared to occlude further modulation of I$\sb{\rm K,S}$ by serotonin, but did not block serotonin-induced modulation of the voltage-dependent delayed rectifier K$\sp+$ current (I$\sb{\rm K,V}$). These results suggest that buccalin A converges on some, but not all, of the same subcellular modulatory pathways as serotonin.^ In order to begin to understand neuromodulation in a more physiological context for the tail-siphon withdrawal reflex, the modulatory circuitry for the tail-withdrawal circuit was examined. Mechanoafferent neurons in the J cluster of the cerebral ganglion were identified as elements of a modulatory circuit for the reflex. Excitatory and inhibitory connections were observed between the J cells and the pleural sensory neurons, the tail motor neurons, and several classes of interneurons for the tail-siphon withdrawal circuit. The J cells produced both fast and slow PSPs in these neurons. Of particular interest was the ability of the J cells to produce slow EPSPs in the pleural sensory neurons. These slow EPSPs were associated with an increase in the excitability of the sensory neurons. The J cells appear to mediate both sensory and modulatory inputs to the circuit for the tail-siphon withdrawal reflex from the anterior part of the animal. ^

Convergent etiology of Eker rat and human uterine leiomyoma

The Eker rat model has allowed researchers the unique opportunity to study the tumorigenesis of spontaneously occurring uterine leiomyoma. Animals in this line harbor a germline mutation in the tuberous sclerosis complex-2 (Tsc-2) tumor suppressor gene and develop uterine leiomyomas at a rate of ∼65%. Primary leiomyomas obtained from humans and Eker rats along with Eker-derived leiomyoma cell lines were used in studies described herein to determine the effect of PPARγ ligand treatment on the proliferation of this cell type and to determine the role of tuberin and p27Kip1 in the etiology of this tumor type. Treatment of leiomyoma cells of human and rat origin with PPARγ-activating compounds resulted in decreased proliferation. Additionally, PPARγ ligands inhibited estrogen-dependent gene transactivation in Eker-derived leiomyoma cells suggesting that nuclear receptor cross-talk may exist between PPAR and the ER and may be responsible for the inhibition of proliferation in this cell type. Loss of tuberin, the product of the TSC-2 gene, is associated with Eker rat leiomyoma development while the role of this tumor suppressor in human leiomyoma development is unknown. Data herein show that tuberin expression is diminished in 25% of human leiomyomas tested. Additionally, we observed diminished p27 Kip1 expression in 80% of human uterine leiomyomas compared to normal myometrium. Interestingly, the loss of tuberin expression in human leiomyoma was associated with cytoplasmic p27Kip1 accumulation in this cell type. Furthermore, tuberin-null Eker rat leiomyomas and derived cell lines had predominantly cytoplasmic p27Kip1 compared to tuberin-expressing normal myometrium. Taken together, our data show that human and Eker rat leiomyoma proliferation is inhibited upon PPARγ treatment and that the etiology of human and Eker rat leiomyoma converge at loss of p27Kip1 function. Furthermore, our data indicate that the loss of p27 Kip1 function is mediated by loss of expression (in 80% of human leiomyoma) or cytoplasmic localization potentially resulting from the loss of tuberin. ^