Protein-Protein Interactions That Regulate Neurotransmitter Release from Retinal Ribbon Synapses

Protein-Protein Interactions That Regulate Neurotransmitter Release from Retinal Ribbon Synapses Photoreceptors and bipolar cells in the retina form specialized chemical synapses called ribbon synapses. This type of synapse differs physiologically from “conventional” chemical synapses. While “conventional” synapses exocytose neurotransmitter-filled vesicles in an all-or-none fashion in response to an action potential, a retinal ribbon synapse can release neurotransmitter tonically (sustained) in response to graded changes in membrane potential or phasically (transient) in response to a large change in membrane potential. Synaptic vesicle exocytosis is a tightly controlled process involving many protein-protein interactions. Therefore, it is likely that the dissimilarity in the release properties of retinal ribbon synapses and conventional synapses is the result of molecular differences between the two synapse types. Consistent with this idea, previous studies have demonstrated that ribbon synapses in the retina do not contain the t-SNARE (target-soluble N-ethylmaleimide-sensitive factor attachment protein receptor) syntaxin 1A that is found in conventional synapses of the nervous system. In contrast, ribbon synapses of the mammalian retina contain the related isoform, syntaxin 3B. Given that SNARE proteins play an important role in neurotransmitter release in conventional synapses, the purpose of this study was to characterize syntaxin 3B in order to elucidate what role this protein plays in neurotransmitter release from retinal ribbon synapses. Using molecular and biochemical techniques, it was demonstrated that syntaxin 3B is a binding partner of several presynaptic proteins that play a important role in synaptic vesicle exocytosis from retinal ribbon synapses and it is an evolutionarily conserved protein.

PANEL DISCUSSION: "Medical Ethics, Eugenics, and the Holocaust"

A panel discussion moderated by Dr. Thomas R. Cole, McGovern Chair in Medical Humanities and Director of the John P. McGovern Center for Humanities and Ethics at the University of Texas Health Science Center in Houston. Panelists include: Rabbi Samuel E. Karff, Rabbi Emeritus of Congregation Beth Israel and Associate Director of the John P. McGovern Center for Humanities and Ethics and Visiting Professor in the Department of Family Medicine at the University of Texas Health Science Center at the Texas Medical Center. Cardinal DiNardo, the second Archbishop of the Archdiocese of Galveston-Houston and the first cardinal archbishop from a diocese in the Southern United States. Dr. Sheldon Rubenfeld, Clinical Professor of Medicine at Baylor College of Medicine. He is Board Certified in Internal Medicine and in Endocrinology, Diabetes, and Metabolism, and is a Fellow in both the American College of Physicians and the American College of Endocrinology. Dr. Rubenfeld has taught "Healing by Killing: Medicine During the Third Reich" for three years and "Jewish Medical Ethics" for seven years at Baylor College of Medicine. He created a six-month program about Medicine and the Holocaust at Holocaust Museum Houston, including an exhibit entitled How Healing Becomes Killing: Eugenics, Euthanasia, Extermination and a series of lectures by distinguished speakers entitled "The Michael E. DeBakey Medical Ethics Lecture Series".

Sex Trafficking of Minors in the U.S.: Implications for Policy, Prevention and Research

Context: Information currently available on the trafficking of minors in the U.S. for commercial sexual exploitation includes approximations of the numbers involved, risk factors that increase the likelihood of victimization and methods of recruitment and control. However, specific characteristics about this vulnerable population remain largely unknown. Objective: This article has two distinct purposes. The first is to provide the reader with an overview of available information on minor sex trafficking in the U.S. The second is to present findings and discuss policy, research, and educational implications from secondary data analysis of 115 cases of minor sex trafficking in the U.S. Design: Minor sex trafficking cases were identified through two main venues - a review of U.S. Department of Justice press releases of human trafficking cases and an online search of media reports. Searches covered the time period from October 28, 2000, which coincided with the passage of the VTVPA through October 31, 2009. Cases were included in analysis if the incident involved at least one victim under the age of 18, occurred in the U.S., and at least one perpetrator had been arrested, indicted, or convicted. Results: A total of 115 separate incidents involving at least 153 victims were located. These occurrences involved 215 perpetrators, with the majority of them having been convicted (n = 117, 53.4%), The number of victims involved in a single incident ranged from 1 to 9. Over 90% of victims were female who ranged in age from 5 to 17 years. There were more U.S. minor victims than those from other countries. Victims had been in captivity from less than 6 months to 5 years. Minors most commonly fell into exploitation through some type of false promise indicated (16.3%, n = 25), followed by kidnapping (9.8%, n = 15). Over a fifth of the sample (22.2%, n = 34) were abused through two commercial sex practices, with almost all (94.1%, n = 144) used in prostitution. One of every five victims (24.8%, n = 38) had been advertised on an Internet website. Conclusions: Results of a review of known information about minor sex trafficking and findings from analysis of 115 incidents of the sex trafficking of youth in the U.S. indicate a need for stronger legislation to educate various professional groups, more comprehensive services for victims, stricter laws for pimps and traffickers, and preventive educational interventions beginning at a young age.

CYTOGENETIC AND DNA CONTENT ANALYSIS IN MULTIPLE MYELOMA

In this dissertation, the cytogenetic characteristics of bone marrow cells from 41 multiple myeloma patients were investigated. These cytogenetic data were correlated with the total DNA content as measured by flow cytometry. Both the cytogenetic information and DNA content were then correlated with clinical data to determine if diagnosis and prognosis of multiple myeloma could be improved.^ One hundred percent of the patients demonstrated abnormal chromosome numbers per metaphase. The average chromosome number per metaphase ranged from 42 to 49.9, with a mean of 44.99. The percent hypodiploidy ranged from 0-100% and the percent hyperdiploidy from 0-53%. Detailed cytogenetic analyses were very difficult to perform because of the paucity of mitotic figures and the poor chromosome morphology. Thus, detailed chromosome banding analysis on these patients was impossible.^ Thirty seven percent of the patients had normal total DNA content, whereas 63% had abnormal amounts of DNA (one patient with less than normal amounts and 25 patients with greater than normal amounts of DNA).^ Several clinical parameters were used in the statistical analyses: tumor burden, patient status at biopsy, patient response status, past therapy, type of treatment and percent plasma cells. Only among these clinical parameters were any statistically significant correlations found: pretreatment tumor burden versus patient response, patient biopsy status versus patient response and past therapy versus patient response.^ No correlations were found between percent hypodiploid, diploid, hyperdiploid or DNA content, and the patient response status, nor were any found between those patients with: (a) normal plasma cells, low pretreatment tumor mass burden and more than 50% of the analyzed metaphases with 46 chromosomes; (b) normal amounts of DNA, low pretreatment tumor mass burden and more than 50% of the metaphases with 46 chromosomes; (c) normal amounts of DNA and normal quantities of plasma cells; (d) abnormal amounts of DNA, abnormal amounts of plasma cells, high pretreatment tumor mass burden and less than 50% of the metaphases with 46 chromosomes.^ Technical drawbacks of both cytogenetic and DNA content analysis in these multiple myeloma patients are discussed along with the lack of correlations between DNA content and chromosome number. Refined chromosome banding analysis awaits technical improvements before we can understand which chromosome material (if any) makes up the "extra" amounts of DNA in these patients. None of the correlations tested can be used as diagnostic or prognostic aids for multiple myeloma. ^

Unintended pregnancy: Attitudes toward contraception of women obtaining abortions

Forty-nine percent of pregnancies in the United States are unintended and significant numbers of pregnancies are unintended for women of all ages. One possible reason for the high rate is that while 85% of women at risk for an unintended pregnancy use contraception, negative attitudes about the method used make them poor contraceptors. Negative attitudes may prevent the remaining 15% of women from using any method of birth control. This study examined adult women's attitudes toward contraception and its use to see if attitudes correlate with unintended pregnancy. ^ To obtain a sample of women experiencing unintended pregnancies, women obtaining therapeutic abortions were surveyed since almost all women obtaining therapeutic abortions are experiencing an unintended pregnancy. The study used a cross-sectional survey design and included 312 women obtaining abortions at the Planned Parenthood Surgical Services Clinic in Houston in the latter half of 1999. ^ The responses revealed a lack of knowledge about the safety and effectiveness of contraception, particularly for methods other than oral contraceptives and condoms. Thirty-four percent of the participants were uncomfortable buying contraception. While 71% of the participants said their physician recommended their use of contraception, 17% were unsure and 35% did not talk to their physician about contraception on a regular basis. ^ The attitudes of women using contraception were compared with those not using contraception and many differences were seen. Women not using contraception responded with more ‘unsure’ answers and believed contraception was more difficult to use. They felt planning ahead for the use of contraception interfered with the enjoyment of sex (p-value = 0.06). They were less likely to use contraception if their partner disapproved (p-value = 0.01) and more of them believed their church disapproved of contraception (p-value = 0.02). In comparison, women using contraception had negative attitudes about the safety of the pill (p-values = 0.01–0.08) and the effectiveness of the condom (p-value = 0.04). Therefore, the negative attitudes women using contraception had about contraception may interfere with their effective use of birth control. Those not using contraception were found to hold attitudes that may contribute to their non-use of contraception. ^

Pediatric antiretroviral adherence and child disclosure in Botswana

The scale-up of antiretrovirals (ARVs) to treat HIV/AIDS in Africa has been rapid over the last five years. Botswana was the first African nation to roll out a comprehensive ARV program, where ARVs are available to all citizens who qualify. Excellent adherence to these ARVs is necessary to maintain HIV suppression and on-going health of all individuals taking them. Children rely almost entirely on their caregivers for the administration of these medications, and very little research has been done to examine the factors which affect both adherence and disclosure to the child of their HIV status. ^ Methods. This cross-sectional study used multiple methods to examine adherence, disclosure, and stigma across various dimensions of the child and caregiver's lives, including 30 caregiver questionnaires, interviewer-administered 3-day adherence recalls, pharmacy pill counts, and chart reviews. Fifty in-depth interviews were conducted with caregivers, male caregivers, teenagers, and health care providers. ^ Results. Perceived family stigma was found to be a predictor of excellent adherence. After controlling for age, children who live with their mothers were significantly less likely to know their HIV status than children living with any other relative (OR=0.403, p=0.014). Children who have a grandmother living in the household or taking care of them each day are significantly more likely to have optimal adherence than children who don't have grandmother involvement in their daily lives. ^ Discussion. Visible illness plays an intermediary role between adherence and perceived family stigma: Caregivers know that ARVs suppress physical manifestations of HIV, and in an effort to avoid unnecessary disclosure of the child's status to family members, therefore have children with excellent adherence. Grandmothers play a vital role in supporting the care and treatment of children in Botswana. ^

An assessment of differences in pediatric dental services provided for a Medicaid population when compared to a federally subsidized (military) clinic

Reimbursement for dental services performed for children receiving Medicaid is reimbursed per service while dental treatment for military dependents provided at a military installation is neither directly reimbursable to those providing the care nor billed to those receiving the care. The purpose of this study was to compare pediatric dental services provided for a Medicaid population to a federally subsidized military facility to compare treatment choices and subsequent costs of care. It was hypothesized that differences in dental procedures for Medicaid and military dependent children would exist based upon treatment philosophy and payment method. A total of 240 records were reviewed for this study, consisting of 120 Medicaid patients at the University of Texas Health Science Center at San Antonio (UTHSCSA) and 120 military dependents at Wilford Hall Medical Center (WHMC), Lackland Air Force Base, San Antonio. Demographic data and treatment information were abstracted for children receiving dental treatment under general anesthesia between 2002 and 2006. Data was analyzed using the Wilcoxon rank sum test, Kruskal-Wallis test, and Fisher's exact test. The Medicaid recipients treated at UTHSCSA were younger than patients at WHMC (40.2 vs. 49.8 months, p<.001). The university also treated significantly more Hispanic children than WHMC (78.3% vs. 30.0%, p<.001). Children at UTHSCSA had a mean of 9.5 decayed teeth and were treated with 2.3 composite fillings, 0 amalgam fillings, 5.6 stainless steel crowns, 1.1 pulp therapies, 1.6 extractions, and 1.0 sealant. Children at WHMC had a mean of 8.7 decayed teeth and were treated with 1.4 composite fillings, 0.9 amalgam fillings, 5.6 stainless steel crowns, 1.7 pulp therapies, 0.9 extractions, and 2.1 sealants. The means of decayed teeth, total fillings, and stainless steel crowns were not statistically different. UTHSCSA provided more composite fillings (p<.001), fewer amalgam fillings (p<.001), fewer pulp therapies (p <.001), more extractions (p=.01), and fewer sealants (p<.001) when compared to WHMC. Age and gender did not effect decay rates, but those of Hispanic ethnicity did experience more decay than non-Hispanics (9.5 vs. 8.6, p=.02). Based upon Texas Medicaid reimbursement rates from 2006, the cost for dental treatment at both sites was approximately $650 per child. The results of this study do not support the hypothesis that Medicaid providers provide less conservative therapies, which would be more costly, care when compared to a military treatment center. ^

Selection bias and the cross-validation of regression models for prediction

Strategies are compared for the development of a linear regression model with stochastic (multivariate normal) regressor variables and the subsequent assessment of its predictive ability. Bias and mean squared error of four estimators of predictive performance are evaluated in simulated samples of 32 population correlation matrices. Models including all of the available predictors are compared with those obtained using selected subsets. The subset selection procedures investigated include two stopping rules, C$\sb{\rm p}$ and S$\sb{\rm p}$, each combined with an 'all possible subsets' or 'forward selection' of variables. The estimators of performance utilized include parametric (MSEP$\sb{\rm m}$) and non-parametric (PRESS) assessments in the entire sample, and two data splitting estimates restricted to a random or balanced (Snee's DUPLEX) 'validation' half sample. The simulations were performed as a designed experiment, with population correlation matrices representing a broad range of data structures.^ The techniques examined for subset selection do not generally result in improved predictions relative to the full model. Approaches using 'forward selection' result in slightly smaller prediction errors and less biased estimators of predictive accuracy than 'all possible subsets' approaches but no differences are detected between the performances of C$\sb{\rm p}$ and S$\sb{\rm p}$. In every case, prediction errors of models obtained by subset selection in either of the half splits exceed those obtained using all predictors and the entire sample.^ Only the random split estimator is conditionally (on $\\beta$) unbiased, however MSEP$\sb{\rm m}$ is unbiased on average and PRESS is nearly so in unselected (fixed form) models. When subset selection techniques are used, MSEP$\sb{\rm m}$ and PRESS always underestimate prediction errors, by as much as 27 percent (on average) in small samples. Despite their bias, the mean squared errors (MSE) of these estimators are at least 30 percent less than that of the unbiased random split estimator. The DUPLEX split estimator suffers from large MSE as well as bias, and seems of little value within the context of stochastic regressor variables.^ To maximize predictive accuracy while retaining a reliable estimate of that accuracy, it is recommended that the entire sample be used for model development, and a leave-one-out statistic (e.g. PRESS) be used for assessment. ^