BETA2/NeuroD1 is a bHLH transcription factor that is expressed during development in the mammalian pancreas and in many locations in the central and peripheral nervous systems. During inner ear ontogenesis, it is present in both sensory ganglion neurons and sensory epithelia. Although studies have shown that BETA2/NeuroD1 is important in the development of the hippocampal dentate gyrus and the cerebellum, its functions in the peripheral nervous system and in particular in the inner ear are unclear. Mice carrying a BETA2/NeuroD1 null mutation exhibit behavioral abnormalities suggestive of an inner ear defect, including lack of responsiveness to sound, hyperactivity, head tilting, and circling. Here we show that these defects can be explained by a severe reduction of sensory neurons in the cochlear-vestibular ganglion (CVG). A developmental study of CVG formation in the null demonstrates that BETA2/NeuroD1 does not play a primary role in the proliferation of neuroblast precursors or in their decision to become neuroblasts. Instead, the reduction in CVG neuron number is caused by a combination both of delayed or defective delamination of CVG neuroblast precursors from the otic vesicle epithelium and of enhanced apoptosis both in the otic epithelium and among those neurons that do delaminate to form the CVG. There are also defects in differentiation and patterning of the cochlear duct and sensory epithelium and loss of the dorsal cochlear nucleus. BETA2/NeuroD1 is, thus, the first gene to be shown to regulate neuronal and sensory cell development in both the cochlear and vestibular systems.

BackgroundStudies reveal that electronic cigarette (e-cigarette) and hookah use are increasing among adolescents and young adults. However, the long-term health effects are unknown, especially with regards to pregnancy. Because of the increased use in women of reproductive age, and the unknown long-term health risks, our primary objectives were to determine the perceived risks of e-cigarette and hookah use in pregnancy, and learn common colloquial terms associated with e-cigarettes. Furthermore, we sought to determine if there is a stigma associated with e-cigarette use in pregnancy.MethodsEleven focus groups including 87 participants were conducted immediately following regularly scheduled CenteringPregnancy® prenatal care with women at three different clinics in the greater Houston area. A minimum of two facilitators led the groups, using ten lead-in prompts, with Spanish translation as necessary. Facilitators took notes which were compared immediately following each group discussion and each group was audio recorded and transcribed. Three facilitators utilized NVivo 9.0 software to organize the transcribed data into nodes to identify major themes. To increase rigor, transcripts were further analyzed by two obstetricians who were instructed to find the major themes.ResultsAnalyses revealed contradicting themes concerning e-cigarette use. In general, e-cigarettes were perceived as safer alternatives to regular tobacco cigarettes, especially if used as smoking cessation devices. A major theme is that use in pregnancy is harmful to the fetus. However, it was perceived that use for smoking cessation in pregnancy may have fewer side effects. We found that a common term for e-cigarettes is “Blu.” In our discussion of hookah use, participants perceived use as popular among teenagers and that use in pregnancy is dangerous for the fetus.ConclusionsAlthough a strong theme emerged against hookah use, we found contradicting themes in our discussions on e-cigarette use in pregnancy. It is possible that e-cigarette use will not carry the same stigma as regular cigarette smoking in pregnancy. In addition, the impression of e-cigarettes as a healthier alternative to smoking may influence use in pregnancy. Clinicians need to be prepared for questions of e-cigarette safety and efficacy as smoking cessation devices from their pregnant patients who smoke, and women who smoke and are planning to become pregnant.

Prestin, a member of the SLC26A family of anion transporters, is a polytopic membrane protein found in outer hair cells (OHCs) of the mammalian cochlea. Prestin is an essential component of the membrane-based motor that enhances electromotility of OHCs and contributes to frequency sensitivity and selectivity in mammalian hearing. Mammalian cells expressing prestin display a nonlinear capacitance (NLC), widely accepted as the electrical signature of electromotility. The associated charge movement requires intracellular anions reflecting the membership of prestin in the SLC26A family. We used the computational approach of evolutionary trace analysis to identify candidate functional (trace) residues in prestin for mutational studies. We created a panel of mutations at each trace residue and determined membrane expression and nonlinear capacitance associated with each mutant. We observe that several residue substitutions near the conserved sulfate transporter domain of prestin either greatly reduce or eliminate NLC, and the effect is dependent on the size of the substituted residue. These data suggest that packing of helices and interactions between residues surrounding the "sulfate transporter motif" is essential for normal prestin activity.

Background Gestational diabetes mellitus (GDM) is one of most common complications of pregnancy, with incidence rates varying by maternal age, race/ethnicity, obesity, parity, and family history. Given its increasing prevalence in recent decades, co-variant environmental and sociodemographic factors may be additional determinants of GDM occurrence. Objectives We hypothesized that environmental risk factors, in particular measures of the food environment, may be a diabetes contributor. We employed geospatial modeling in a populous U.S. county to characterize the association of the relative availability of fast food restaurants and supermarkets to GDM. Study Design Utilizing a perinatal database with over 4900 encoded antenatal and outcome variables inclusive of zip code data, 8912 consecutive pregnancies were analyzed for correlations between GDM and food environment based on county-wide food permit registration data. Linkage between pregnancies and food environment was achieved on the basis of validated 5 digit zip code data. The prevalence of supermarkets and fast food restaurants per 100,000 inhabitants for each zip code were gathered from publicly available food permit sources. In order to independently authenticate our findings with objective data, we measured hemoglobin A1c (HbA1c) levels as a function of geospatial distribution of food environment in a matched subset (n=80). Results Residence in neighborhoods with a high prevalence of fast food restaurants (fourth quartile) was significantly associated with an increased risk of developing GDM (relative to first quartile, aOR: 1.63 [95% CI 1.21–2.19]). In multivariate analysis, this association held true after controlling for potential confounders (p=0.002). Measurement of HbA1c levels in a matched subset were significantly increased in association with residence in a zip code with a higher fast food/supermarket ratio (n=80, r=0.251 p<0.05). Conclusions As demonstrated by geospatial analysis, a relationship of food environment and risk for gestational diabetes was identified.

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secretion of an altered panel of cytokines versus the CTL group. These findings may propose a novel mechanism to explain normal and premature cervical remodeling.

<p>  </p> <p>Jorge Enrique Delgado-Hachmeister, M.D., M.P.H, M.Sc., Ph.D. 1,2, Cindy Shope 5, Daniel Chelius 3, M.D., John S. Oghalai 4, M.D., Raye L. Alford, Ph.D. 5, Bobby R. Alford† 5, M.D., Brenda Farrell, Ph.D 5, Lucy Handscomb, Ph.D. 2, Jonathan Ashmore, Ph.D. 2, Dan Jagger, Ph.D. 2, Issam Saliba, M.D. 7, Sengyoth Vilaysane, M.D. 1, Thomas Lenarz, MD 8, Anat Shahar, Ph.D. 6</p> <p>Jorge E. Delgado-Hachmeister, M.D. </p> <p>La Salle University</p> <p>Mexican Faculty of Medicine</p> <p>Islas Marianas No. 9, Fracc. Residencial Campestre Chiluca, Atizapán de Zaragoza, C.P. 52930, Edo. de Mex., México</p> <p>Mobile: + 52 55 10 52 81 58</p> <p>Home Phone: + 52 55 50 19 17 36</p> <p>e-mail: jorgeenriquedelgadoh@hotmail.com</p> <p><strong>Abstract</strong> </p> <p>We decided to investigate if quinine modifies the nonlinear capacitance of the mammalian outer hair cell of the hearing organ of Corti. We used isolated outer hair cells of guinea pigs and performed electrophysiological recordings. We tracked the Voltage at Peak Capacitance of the outer hair cell at different quinine concentrations and also measured the modifications of the bell-shaped curve of the outer hair cell under different quinine concentrations. We also studied if quinine induces apoptosis of the outer hair cell. We show that quinine shifts this bell-shaped curve towards depolarized potentials (>90 mV) and induces a small reduction on the gain (up to 13%). The shifts are fully reversible at low concentrations (< 1 mM) but only partially reversible at high concentrations (> 5 mM). A histological study of guinea pig OHCs confirms that quinine triggers apoptosis in a concentration dependent manner and produces large pores in the plasma membrane at high concentrations. At therapeutic concentrations of quinine that are used to treat malaria (0.04 mM) we find that quinine shifts the voltage at peak capacitance by 1.5 to 3.5 mV. This is significantly greater than observed for chloropromazine ( < 1 mV) and furosemide (no shift) at their relevant clinical concentrations. We demonstrate for the first time that the plausible mechanism by which quinine increases hearing thresholds is by partitioning into the membrane of OHCs where it affects the membrane-based motor mechanism underlying electromotility.</p> <p><strong>Key Words: </strong>outer hair cells, voltage at peak capacitance, electromotility, apoptosis, quinine, amphipaths</p> <p>While the actions of quinine on outer hair cell physiology of mammalians have been previously investigated, it remains unknown, the precise mechanism by which quinine induces reversible tinnitus and hearing loss. Also it is unknown why quinine produces in some rare cases irreversible hearing loss. Here we provide definitive evidence that quinine at therapeutic levels for the treatment of <em>Falciparum</em> malaria modifies outer hair cell physiology and electromotilty and also triggers apoptosis in outer hair cells. Proving that the main mechanism by which quinine modifies hearing thresholds is by modifying outer hair cell physiology, probably by interacting with prestin.</p> <p><strong>Level of Evidence:</strong> NA</p>

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