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1. David L. Hill, MD* 1. *Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, NC Clinicians should be aware of roles that social media play in child and adolescent health and development and be prepared to guide parents and patients toward best practices in social media use. After completing this article, readers should be able to: 1. Recognize the major benefits and risks posed by social media throughout the course of child development. 2. Become comfortable addressing the roles that social media play in the most important aspects of child health and development, including psychosocial development, academic performance, healthy weight and sleep habits, and minimizing high-risk behaviors. Dr Victor Strasburger wrote in 2010: “The media are not the leading cause of any health problem in childhood or adolescence. However, they can make a substantial contribution to virtually every health concern that pediatricians and parents have about young people—aggression, sex, drugs, obesity, self-image and eating disorders, depression and suicide, even learning disorders and academic achievement.” (1) Since that time, the use of digital media has proliferated, along with our understanding of how such media affect child and adolescent health and development. To Dr Strasburger’s list we would now add risks including sleep deprivation, problematic Internet use, and Internet gaming disorder. At the same time, this assessment overlooks some of the potential benefits that social media have to contribute to children’s education, connectedness, and resilience. Although many pediatricians feel comfortable using some social media platforms, fewer counsel parents and patients on social media use. The American …

Neuronal activity plays critical roles in the development of sensory circuits in the mammalian brain. Experimental procedures are now available to alter the function of specific taste transduction pathways and have been especially useful in studying how stimulus-specific taste activity influences the development of central gustatory circuits. We previously used a mouse knock-out (KO) model in which the transduction channel necessary for sodium taste is removed from taste bud cells throughout life. In these KO mice, the terminal fields that carry taste information from taste buds into the nucleus of the solitary tract (NST) fail to mature, suggesting that sodium-elicited taste activity is important for the proper development of central gustatory circuits. Here, we tested the hypothesis that the development and maintenance of the dendritic architecture of NST relay cells, the primary postsynaptic partner of gustatory nerve terminal fields, are similarly dependent on sodium-elicited taste activity. The dendritic fields of NST relay cells, from adult male and female mice in which the α-subunit of the epithelial sodium channel (αENaC) was conditionally deleted in taste bud cells throughout life, were up to 2.4× larger and more complex than that of age-matched control mice. Interestingly, these differences in dendritic architecture did not appear until after the age when terminal fields begin “pruning,” after postnatal day (P)20. Overall, our results suggest that ENaC-mediated sodium taste activity is necessary for the maintenance of dendritic fields of relay cells in the gustatory NST.

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Both the lateral olfactory tract (LOT) and anterior limb of the anterior commissure (AC) carry olfactory information. The LOT forms the projection from the olfactory bulb to the ipsilateral olfactory cortices, while the AC carries odor information across the midline to the contralateral olfactory cortex and bulb. The LOT and AC differ on a number of dimensions, including early development and functional onset. The present work, examining their myelination in mice, reveals additional important differences. For example, the LOT initiates myelination 3–4 days earlier than the AC, evidenced by both an earlier increase in myelin basic protein staining seen with immunohistochemistry and an earlier appearance of myelinated fibers using electron microscopy. While both exhibit a period of rapid myelination, it occurs 4–5 days earlier in the LOT than the AC. The tracts also respond differently to early sensory restriction. Unilateral naris occlusion from the day after birth to postnatal day 30 had no consistent effects on the AC, but resulted in significantly thinner myelin sheaths relative to axon caliber in the LOT. Finally, the two tracts differ structurally (the LOT contains larger, more densely packed axons with significantly thicker myelin sheaths resulting in a conduction velocity that is more than twice as fast as the AC). The findings indicate that these two large, accessible tracts provide an important means for studying brain maturation due to basic differences in both the timing of their maturation and general organization.

Taste nerves readily regenerate to reinnervate denervated taste buds; however, factors required for regeneration have not yet been identified. When the chorda tympani nerve is sectioned, expression of brain-derived neurotrophic factor (BDNF) remains high in the geniculate ganglion and lingual epithelium, despite the loss of taste buds. These observations suggest that BDNF is present in the taste system after nerve section and may support taste nerve regeneration. To test this hypothesis, we inducibly deleted Bdnf during adulthood in mice. Shortly after Bdnf gene recombination, the chorda tympani nerve was unilaterally sectioned causing a loss of both taste buds and neurons, irrespective of BDNF levels. Eight weeks after nerve section, however, regeneration was differentially affected by Bdnf deletion. In control mice, there was regeneration of the chorda tympani nerve and taste buds reappeared with innervation. In contrast, few taste buds were reinnervated in mice lacking normal Bdnf expression such that taste bud number remained low. In all genotypes, taste buds that were reinnervated were normal-sized, but non-innervated taste buds remained small and atrophic. On the side of the tongue contralateral to the nerve section, taste buds for some genotypes became larger and all taste buds remained innervated. Our findings suggest that BDNF is required for nerve regeneration following gustatory nerve section.

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A key process in central sensory circuit development involves activity-dependent “pruning” of early exuberant terminals. Here, we studied gustatory terminal field maturation in the postnatal mouse nucleus of the solitary tract (NST) during normal development and in mice where their mothers were fed a low NaCl diet for a limited period during early embryonic development. “Pruning” of terminal fields in controls involved the complement system and appears driven by NaCl-elicited taste activity. In contrast, offspring of mothers with the early dietary manipulation failed to “prune” gustatory terminal fields even though peripheral taste activity developed normally. The ability to “prune” in these mice was rescued by activating myeloid cells postnatally, and conversely, “pruning” was arrested in controls with the loss of myeloid cell function. The altered “pruning” and myeloid cell function appears programmed before the peripheral gustatory system is assembled and corresponds to the embryonic period when microglia progenitors migrate into the brain.

The rodent peripheral gustatory system is especially plastic during early postnatal development and maintains significant anatomical plasticity into adulthood. Thus, taste information carried from the tongue to the brain is built and maintained on a background of anatomical circuits that have the capacity to change throughout the animal9s lifespan. Recently, the neurotrophin brain-derived neurotrophic factor (BDNF) was shown to be required in the tongue to maintain normal levels of innervation in taste buds at adulthood, indicating that BDNF is a key molecule in the maintenance of nerve/target matching in taste buds. Here, we tested whether maintenance of the central process of these gustatory nerves at adulthood also relies on BDNF by using male and female transgenic mice with inducible CreERT2 under the control of the keratin 14 promoter or under control of the ubiquitin promoter to remove Bdnf from the tongue or from all tissues, respectively. We found that the terminal fields of gustatory nerves in the nucleus of the solitary tract were expanded when Bdnf was removed from the tongue at adulthood and with even larger and more widespread changes in mice where Bdnf was removed from all tissues. Removal of Bdnf did not affect numbers of ganglion cells that made up the nerves and did not affect peripheral, whole-nerve taste responses. We conclude that normal expression of Bdnf in gustatory structures is required to maintain normal levels of innervation at adulthood and that the central effects of Bdnf removal are opposite of those in the tongue. SIGNIFICANCE STATEMENT BDNF plays a major role in the development and maintenance of proper innervation of taste buds. However, the importance of BDNF in maintaining innervation patterns of gustatory nerves into central targets has not been assessed. Here, we tested whether Bdnf removal from the tongue or from all structures in adult mice impacts the maintenance of how taste nerves project to the first central relay. Deletion of Bdnf from the tongue and from all tissues led to a progressively greater expansion of terminal fields. This demonstrates, for the first time, that BDNF is necessary for the normal maintenance of central gustatory circuits at adulthood and further highlights a level of plasticity not seen in other sensory system subcortical circuits.

Since creating its Road Improvement Program (RIP), the Insurance Corporation of British Columbia (ICBC) has invested more than $110 million in road safety improvements in British Columbia, Canada. The RIP partners with provincial road authorities to identify problem locations and implement interventions to improve road safety. The level of ICBC investment in a safety project has been based on the potential for collision reduction associated with the proposed improvements. The goal has been to target collision-prone locations to reduce frequency and severity of collisions and, therefore, auto insurance claim costs to ICBC. Although the projects funded by the RIP were entirely necessary and effective, the reactive nature of the program did not allow for investments at locations that were deemed to be high risk but that did not have a significant history of collisions. In recognition that some attention should be given to these high-risk, low-crash locations, a new program was developed to provide funding to support road improvement projects that were not based on a history of collisions. The new program, referred to as the Proactive Road Safety Program, complemented the reactive program through the provision of funding support for projects that could prevent, rather than reduce, collisions. This paper describes the rationale and methodology developed for the Proactive Road Safety Program to quantify road safety risk and assign an economic value to justify funding for proactive road safety projects.

Objective To determine whether follicular fluid (FF) cortisol levels affect cumulus cell (CC) lipid content during oocyte meiotic resumption, and whether CCs express genes for glucocorticoid action. Design Prospective cohort study. Setting Academic medical center. Patient(s) Thirty-seven nonobese women underwent ovarian stimulation for in vitro fertilization (IVF). Intervention(s) At oocyte retrieval, FF was aspirated from the first follicle (>16 mm in size) of each ovary and pooled CCs were collected. Main Outcome Measure(s) Follicular fluid cortisol and cortisone analysis was performed with the use of liquid chromatography–tandem mass spectrometry. CCs were stained with lipid fluorescent dye Bodipy FL C16 to determine lipid content with the use of confocal microscopy. Quantitative real-time polymerase chain reaction was used to detect CC gene expression of 11β-hydroxysteroid dehydrogenase (11β-HSD) types 1 and 2, glucocorticoid receptor (NR3C1), lipoprotein lipase (LPL), and hormone-sensitive lipase (HSL). Result(s) Adjusting for maternal age, FF cortisol levels negatively correlated with CC lipid content and positively correlated with numbers of total and mature oocytes. CCs expressed genes for 11β-HSD type 1 as the predominant 11β-HSD isoform, NR3C1, LPL, and HSL. Conclusion(s) FF cortisol levels may regulate CC lipolysis during oocyte meiotic resumption and affect oocyte quality during IVF.

Neuronal activity plays a key role in the development of sensory circuits in the mammalian brain. In the gustatory system, experimental manipulations now exist, through genetic manipulations of specific taste transduction processes, to examine how specific taste qualities (i.e., basic tastes) impact the functional and structural development of gustatory circuits. Here, we used a mouse knock-out model in which the transduction component used to discriminate sodium salts from other taste stimuli was deleted in taste bud cells throughout development. We used this model to test the hypothesis that the lack of activity elicited by sodium salt taste impacts the terminal field organization of nerves that carry taste information from taste buds to the nucleus of the solitary tract (NST) in the medulla. The glossopharyngeal, chorda tympani, and greater superficial petrosal nerves were labeled to examine their terminal fields in adult control mice and in adult mice in which the α-subunit of the epithelial sodium channel was conditionally deleted in taste buds (αENaC knockout). The terminal fields of all three nerves in the NST were up to 2.7 times greater in αENaC knock-out mice compared with the respective field volumes in control mice. The shapes of the fields were similar between the two groups; however, the density and spread of labels were greater in αENaC knock-out mice. Overall, our results show that disruption of the afferent taste signal to sodium salts disrupts the normal age-dependent “pruning” of all terminal fields, which could lead to alterations in sensory coding and taste-related behaviors.SIGNIFICANCE STATEMENTNeural activity plays a major role in the development of sensory circuits in the mammalian brain. To date, there has been no direct test of whether taste-elicited neural activity has a role in shaping central gustatory circuits. However, recently developed genetic tools now allow an assessment of how specific taste stimuli, in this case sodium salt taste, play a role in the maturation of the terminal fields in the mouse brainstem. We found that the specific deletion of sodium salt taste during development produced terminal fields in adults that were dramatically larger than in control mice, demonstrating for the first time that sodium salt taste-elicited activity is necessary for the normal maturation of gustatory inputs into the brain.

Objective: To evaluate the patterns of chromosome abnormalities in embryos derived from intracytoplasmic sperm injection (ICSI) in microsurgical epididymal sperm aspiration (MESA) or testicular sperm extraction (TESE) in comparison to embryos that are derived from naturally ejaculated (EJAC) patients. Materials and methods: Male partners with azoospermia who required MESA or TESE for ICSI were studied for chromosomal abnormalities. The ICSI patients with EJAC sperm served as the control group. Preimplantation genetic diagnosis (PGD) was performed by fluorescence in situ hybridization (FISH). Chromosome abnormalities were categorized as polyploidy, haploidy, aneuploidy, and complex abnormality (which involves more than two chromosomes). Fertilization, embryo development, and patterns of chromosome abnormalities were accessed and evaluated. Results: There was no difference between the MESA, TESE, and EJAC patient groups in the rates of fertilization and pregnancy and the percentages of euploid embryos. In all three groups, less than one-half of the embryos for each group were normal (41 ± 31%, 48 ± 38%, and 48 ± 31% in MESA, TESA, and EJAC, respectively). Complex chromosomal abnormality was significantly more frequent in the MESA group than in the EJAC group (48.3% vs. 26.5%, respectively; p

Animals actively acquire sensory information from the outside world, with rodents sniffing to smell and whisking to feel. Licking, a rapid motor sequence used for gustation, serves as the primary means of controlling stimulus access to taste receptors in the mouth. Using a novel taste-quality discrimination task in head-restrained mice, we measured and compared reaction times to four basic taste qualities (salt, sour, sweet, and bitter) and found that certain taste qualities are perceived inherently faster than others, driven by the precise biomechanics of licking and functional organization of the peripheral gustatory system. The minimum time required for accurate perception was strongly dependent on taste quality, ranging from the sensory-motor limits of a single lick (salt, ∼100 ms) to several sampling cycles (bitter, >500 ms). Further, disruption of sensory input from the anterior tongue significantly impaired the speed of perception of some taste qualities, with little effect on others. Overall, our results show that active sensing may play an important role in shaping the timing of taste-quality representations and perception in the gustatory system.

Haswell, Intel's fourth-generation core processor architecture, delivers a range of client parts, a converged core for the client and server, and technologies used across many products. It uses an optimized version of Intel 22-nm process technology. Haswell provides enhancements in power-performance efficiency, power management, form factor and cost, core and uncore microarchitecture, and the core's instruction set.

Neural activity plays a critical role in the development of central circuits in sensory systems. However, the maintenance of these circuits at adulthood is usually not dependent on sensory-elicited neural activity. Recent work in the mouse gustatory system showed that selectively deleting the primary transduction channel for sodium taste, the epithelial sodium channel (ENaC), throughout development dramatically impacted the organization of the central terminal fields of three nerves that carry taste information to the nucleus of the solitary tract. More specifically, deleting ENaCs during development prevented the normal maturation of the fields. The present study was designed to extend these findings by testing the hypothesis that the loss of sodium taste activity impacts the maintenance of the normal adult terminal field organization in male and female mice. To do this, we used an inducible Cre-dependent genetic recombination strategy to delete ENaC function after terminal field maturation occurred. We found that removal of sodium taste neural activity at adulthood resulted in significant reorganization of mature gustatory afferent terminal fields in the nucleus of the solitary tract. Specifically, the chorda tympani and greater superficial petrosal nerve terminal fields were 1.4× and 1.6× larger than age-matched controls, respectively. By contrast, the glossopharyngeal nerve, which is not highly sensitive to sodium taste stimulation, did not undergo terminal field reorganization. These surprising results suggest that gustatory nerve terminal fields remain plastic well into adulthood, which likely impacts central coding of taste information and taste-related behaviors with altered taste experience.SIGNIFICANCE STATEMENT Neural activity plays a major role in the development of sensory circuits in the mammalian brain. However, the importance of sensory-driven activity in maintaining these circuits at adulthood, especially in subcortical structures, appears to be much less. Here, we tested whether the loss of sodium taste activity in adult mice impacts the maintenance of how taste nerves project to the first central relay. We found that specific loss of sodium-elicited taste activity at adulthood produced dramatic and selective reorganization of terminal fields in the brainstem. This demonstrates, for the first time, that taste-elicited activity is necessary for the normal maintenance of central gustatory circuits at adulthood and highlights a level of plasticity not seen in other sensory system subcortical circuits.

Media, from television to the “new media” (including cell phones, iPads, and social media), are a dominant force in children’s lives. Although television is still the predominant medium for children and adolescents, new technologies are increasingly popular. The American Academy of Pediatrics continues to be concerned by evidence about the potential harmful effects of media messages and images; however, important positive and prosocial effects of media use should also be recognized. Pediatricians are encouraged to take a media history and ask 2 media questions at every well-child visit: How much recreational screen time does your child or teenager consume daily? Is there a television set or Internet-connected device in the child’s bedroom? Parents are encouraged to establish a family home use plan for all media. Media influences on children and teenagers should be recognized by schools, policymakers, product advertisers, and entertainment producers.

The decision to exclude a child from day care or school leads to widespread educational, social, and economic ramifications for affected families. By understanding and improving how these decisions are made, health care providers and policy makers can promote child well-being throughout the state.

Context: Complex cumulus cell-oocyte interactions govern energy utilization during oocyte development. Objective: This study investigates the relationship of cumulus cell mitochondria with oocyte development during ovarian stimulation for in vitro fertilization (IVF). Design: This is a prospective cohort study. Setting: The setting was an academic center. Patients: Thirty women underwent ovarian stimulation for IVF. Intervention(s): Pooled cumulus cells were collected; numbers of total and mature oocytes and two-pronuclear (day 1), six- to eight-cell cleavage (day 3), and blastocyst (day 5) embryos were recorded. Main Outcome Measure(s): A mitochondrial bioassay was developed with Jurkat cells and used with cumulus cells from IVF patients to correlate mitochondrial membrane potential resistance to carbonyl cyanide 3-chlorophenylhydrazone (CCCP) stress with oocyte development and embryogenesis. Results: Adjusting for FSH administered and maternal age, cumulus cell mitochondrial membrane potential resistance to CCCP positively correlated with numbers of total (P < .025) and mature (P < .025) oocytes retrieved. The highest oocyte numbers that correlated with cumulus cell mitochondrial membrane potential occurred in women with the greatest ovarian response to FSH (mitochondrial membrane potential resistance to CCCP-log FSH interactions: total oocytes P < .025; mature oocytes P < .05). Multiple regression modeling of mature oocyte numbers, age, and cumulus cell mitochondrial membrane potential resistance to CCCP showed that numbers of mature oocytes best correlated with numbers of embryos at all stages (P < .0001). Conclusion: During ovarian stimulation for IVF, cumulus cell mitochondrial membrane potential resistance to stress correlates with numbers of total and mature oocytes retrieved, suggesting that cumulus cell–oocyte interactions involving energy facilitate oocyte development.

The chorda tympani nerve (CT), one of three nerves that convey gustatory information to the nucleus of the solitary tract (NTS), displays terminal field reorganization after postnatal day 15 in the rat. Aiming to gain insight into mechanisms of this phenomenon, CT axon projection field and terminal morphology in NTS subdivisions were examined using tract tracing, light microscopy, and immunoelectron microscopy at four postnatal ages: P15, P25, P35, and adult. The CT axons that innervated NTS rostrolateral subdivision both in the adult and in P15 rats were morphologically distinct from those that innervated the rostrocentral, gustatory subdivision. In both subdivisions, CT terminals reached morphological maturity before P15. Rostrolateral, but not rostrocentral axons, went through substantial axonal branch elimination after P15. Rostrocentral CT synapses, however, redistribute onto postsynaptic targets in the following weeks. CT terminal preference for GABAergic postsynaptic targets was drastically reduced after P15. Furthermore, CT synapses became a smaller component of the total synaptic input to the rostrocentral NTS after P35. The results underlined that CT axons in rostrocentral and rostrolateral subdivisions represent two distinct populations of CT input, displaying different morphological properties and structural reorganization mechanisms during postnatal development.

In 1999, the American Academy of Pediatrics (AAP) issued a policy statement addressing media use in children. The purpose of that statement was to educate parents about the effects that media—both the amount and the content—may have on children. In one part of that statement, the AAP recommended that “pediatricians should urge parents to avoid television viewing for children under the age of two years.” The wording of the policy specifically discouraged media use in this age group, although it is frequently misquoted by media outlets as no media exposure in this age group. The AAP believed that there were significantly more potential negative effects of media than positive ones for this age group and, thus, advised families to thoughtfully consider media use for infants. This policy statement reaffirms the 1999 statement with respect to media use in infants and children younger than 2 years and provides updated research findings to support it. This statement addresses (1) the lack of evidence supporting educational or developmental benefits for media use by children younger than 2 years, (2) the potential adverse health and developmental effects of media use by children younger than 2 years, and (3) adverse effects of parental media use (background media) on children younger than 2 years.

Obesity has become a worldwide public health problem. Considerable research has shown that the media contribute to the development of child and adolescent obesity, although the exact mechanism remains unclear. Screen time may displace more active pursuits, advertising of junk food and fast food increases children's requests for those particular foods and products, snacking increases while watching TV or movies, and late-night screen time may interfere with getting adequate amounts of sleep, which is a known risk factor for obesity. Sufficient evidence exists to warrant a ban on junk-food or fast-food advertising in children's TV programming. Pediatricians need to ask 2 questions about media use at every well-child or well-adolescent visit: (1) How much screen time is being spent per day? and (2) Is there a TV set or Internet connection in the child's bedroom?

The Association for Chemoreception Sciences (AChemS) conference offered an exciting mix of both basic and applied research in the chemical senses, which includes central and peripheral processing of gustatory, olfactory, pheromonal, and common chemical stimuli, such as irritants. Levels of analysis ranged from molecular biology to ecology, and attendees included basic and clinical research scientists, scientists from flavors and fragrance industries, and of course, students. Many new and often surprising findings were reported. The following gives a taste (or whiff—depending on which chemosensory researcher you ask!) of some of the new work reported in the invited symposia. In some cases, citations of recent, related published work are included in addition to the symposia content to enable the

To compare the prevalence and severity of periodontal inflammatory disease in subjects with pericoronitis involving a mandibular third molar and those without pericoronitis.Data obtained from healthy adults consecutively enrolled in an institutional review board-approved trial with pericoronitis affecting at least 1 mandibular third molar (study group) were compared with data obtained during the same time frame from subjects without pericoronitis enrolled in a longitudinal third molar monitoring study (comparison group). The periodontal status of each subject was classified based on periodontal probing depths (PD): all PD4 mm, no disease; 1 to 3 PDor=4 mm, incipient disease; at least 4 PDor=4 mm, early disease. Full mouth periodontal probing data were obtained as clinical measures of periodontal status. Data were aggregated to the subject level for the third molar region, the 6 third molar probing sites and the 2 second molar distal probing sites, the non-third molar region, and all remaining probing sites. The prevalence of disease in the study and comparison groups were compared with the Fisher's exact test. As an indicator of disease severity, the number of PDor=4 mm in the 2 groups were compared by the Kruskal-Wallis test. Level of significance was set at P values less than .05.Median age of the 56 subjects with pericoronitis was 23.3 years (IQR 21.3-26.0 years). Fifty-five percent were Caucasian, 16% African American, and 22% Asian. Males and females were almost equally represented in the study group and in the comparison group. The 194 subjects enrolled without pericoronitis were significantly older (32.8 years; IQR 27.2-40.0 years; P.001). Eighty-four percent were Caucasian, 10% African American, and 4% Asian. The proportion of subjects with periodontal inflammatory disease in the third molar region was significantly different between the study and comparison groups. Thirty-one percent of the subjects with pericoronitis had incipient and 55% early disease in the third molar region compared with 25% with incipient and 38% with early disease among subjects without pericoronitis (P = .003). The pattern was similar, but the proportion of subjects was not significantly different between the groups for the non-third molar region. In the study group, 32% had incipient disease and 32% early disease compared with 27% with incipient disease and 22% with early disease in the comparison group (P = .09). The median number of PDor=4 mm for all teeth differed significantly for subjects with and without pericoronitis (median 5 [IQR 3-9] vs 3 [IQR 0-8], respectively; P = .03).Pericoronitis involving mandibular third molars may reflect more underlying periodontal inflammatory disease in affected young adults than might be found in young adults with retained third molars and no pericoronitis.

Prenatal dietary sodium restriction produces profound developmental effects on rat functional taste responses and formation of neural circuits in the brainstem. Converging evidence indicates that the underlying mechanisms for these effects are related to a compromised nutritional state and not to direct stimulus-receptor interactions. We explored whether early malnourishment produces similar functional and structural effects to those seen following dietary sodium restriction by using a protein deficient, sodium replete diet. To determine if early dietary protein-restriction affects the development of the peripheral gustatory system, multi-fiber neurophysiological recordings were made from the chorda tympani nerve and anterograde track tracing of the chorda tympani nerve into the nucleus of the solitary tract (NTS) was accomplished in rats fed a protein-restricted or a control diet (6% and 20%, respectively). The dietary regimens began on embryonic day 7 and continued until rats were used for neurophysiological recordings (postnatal days (P) 35–50) or for chorda tympani terminal field labeling (P40–50). Responses to a concentration series of NaCl, sodium acetate, KCl, and to 0.50 M sucrose, 0.03 M quinine-HCl, and 0.01 N HCl revealed attenuated responses (30–60%) to sodium-specific stimuli in rats fed the 6% protein diet compared with those fed the 20% protein diet. Responses to all other stimuli were similar between groups. Terminal field volumes were nearly twofold larger in protein-restricted rats compared with controls, with the differences located primarily in the dorsal-caudal zone of the terminal field. These results are similar to the results seen previously in rats fed a sodium-restricted diet throughout pre- and postnatal development, suggesting that dietary sodium- and protein-restriction share similar mechanisms in altering gustatory development.

Inergy Automotive Systems examines the internal microscopic structure of polymer and composite materials using various methods, in order to examine the similarity in their behaviour to those structures of a crystalline metallic type.

Neural development is especially vulnerable to environmental influences during periods of neurogenesis and rapid maturation. In fact, short periods of environmental manipulations confined to embryonic development lead to significant changes in morphology and function. A guiding principal emerging from studies of sensory systems is that experimentally induced effects are most dramatic in higher neural levels (e.g., cortex) and primarily involve postnatal synaptic refinements. In contrast to other sensory systems, the gustatory system is particularly susceptible to the effects of deprivation much earlier and with profound changes evident in the brainstem. Here we show that feeding pregnant rats a custom diet featuring a low-sodium content for 9 d before the tongue appears in the fetus produces extensive restructuring of the gustatory brainstem. Rats born to mothers fed the custom diet from embryonic day 3 (E3) to E12 have terminal field volumes of the greater superficial petrosal, chorda tympani, and glossopharyngeal nerves at adulthood that are expanded as much as 10 times beyond that found in rats fed a standard rat chow. The widespread alterations are not attributable to increased numbers of nerve cells, increased target size, or obvious changes in peripheral taste function. Moreover, we show that the limited period of feeding the custom diet has much larger effects than if rats were fed the diet to postweaning ages. Our results suggest that early periods of altered experience, especially during nucleus of the solitary tract neurogenesis, leads to a restructuring of the gustatory brainstem, which in turn may impact the control of sensory and homeostatic processes.

This study was conducted to determine if the completeness of the root formation of mandibular third molars prior to removal affected clinical and health-related quality of life (HRQOL) recovery.Data from HRQOL responses from patients and clinical outcome data were available after third molar surgery conducted by surgeons in community practice and academic centers. The root development of each mandibular third molar on presurgery panoramic radiographs for these patients was assessed by trained clinician observers. Patients were categorized as those with complete root formation (both mandibular third molars had 100% completely formed roots) or as those with incomplete root formation (at least 1 mandibular third molar not completely formed). The proportion of patients who experienced delayed clinical or HRQOL recovery that exceeded a clinically relevant criterion value were compared for these 2 groups of patients using chi2 statistics. Level of significance was set at 0.05.Both mandibular third molars had 100% completely formed roots in 118 patients; at least 1 mandibular third molar was not completely formed in 218 patients. If patients had a mandibular third molar with roots less than 100% complete, they more likely: were female (65% vs 58%), were less than 25 years old (95% vs 54%), P.01, and had not finished high school (59% vs 28%), P.01. For those with incomplete root formation, bone removal for both mandibular third molars was more likely (84% vs 67%), P.01, and the surgeons' overall estimate of degree of difficulty was greater (14/28 vs 12/28), P = .02. Median surgery time did not differ between groups. The proportion of patients who experienced delayed clinical or HRQOL recovery did not differ between the incomplete and complete root formation groups.Incomplete lower third molar root formation presurgery may not be a predictor of better or worse clinical or HRQOL recovery after surgery. Other clinical, demographic, and health indicators should influence surgeons' recommendations and patients' decisions regarding third molar treatment including surgery.

Taste buds are dependent on innervation for normal morphology and function. Fungiform taste bud degeneration after chorda tympani nerve injury has been well documented in rats, hamsters, and gerbils. The current study examines fungiform taste bud distribution and structure in adult C57BL/6J mice from both intact taste systems and after unilateral chorda-lingual nerve transection. Fungiform taste buds were visualized and measured with the aid of cytokeratin 8. In control mice, taste buds were smaller and more abundant on the anterior tip (

The purpose of this study is to describe impaired oocyte fertilization from phospholipase C-zeta (PLC-ζ) deficiency in normal-appearing sperm that was successfully treated using calcium (Ca(2+)) ionophore with intracytoplasmic sperm injection (ICSI) of oocytes matured in vitro.An infertile couple undergoing in vitro fertilization (IVF) experienced failed oocyte fertilization following ICSI with normal-appearing sperm. A semen sample collected from the patient was used to assess the expression of sperm PLC- ζ protein by Western blot analysis and immunofluorescence and PLC-ζ bioactivity by an in vitro model of Ca(2+) release. A second IVF cycle was performed using Ca(2+) ionophore with ICSI to enhance Ca(2+)-induced oocyte activation of oocytes matured in vitro.Sperm PLC-ζ protein deficiency was demonstrated by Western blot analysis and immunofluorescence and confirmed by reduced PLC-ζ bioactivity using an in vitro model of Ca(2+) release. Nevertheless, with this sperm and supplementation of Ca(2+) ionophore following ICSI, fertilization of four of six oocytes matured in vitro was obtained. In addition, four embryos underwent cleavage and two of them reached the blastocyst stage. Transfer of these blastocysts into the uterus led to a single pregnancy and live birth.Deficiency of PLC-ζ in normal-appearing human sperm is associated with impaired Ca(2+)-dependent oocyte activation during ICSI. Under this condition, use of Ca(2+) ionophore following ICSI of oocytes matured in vitro improves embryo developmental competence, possibly through the activation of Ca(2+)-dependent mechanisms governing fertilization and preimplantation embryogenesis.

Institution of a low-NaCl diet beginning at embryonic day 3 and continued throughout pre- and postnatal development has widespread effects on the neuroanatomical organization of the first gustatory relay in the nucleus of the solitary tract. To determine when these effects are expressed postnatally, the terminal field of the chorda tympani nerve was compared between sodium-restricted and sodium-replete rats at postnatal days 15–17, postnatal days 25–27, postnatal days 35–37, and adults. Total terminal fields were significantly larger in postnatal days 35–37 and adult sodium-restricted rats compared with aged-matched controls. The group-related differences appear related more to a remodeling of the terminal field in the dorsal zone of the terminal field in controls. Specifically, the terminal field volume in the dorsal zone in controls decreased dramatically from postnatal days 25–27 to postnatal days 35–37 and then again from postnatal days 35–37 to adulthood. In contrast, the fields did not change during development in sodium-restricted rats. These findings suggest that remodeling of the chorda tympani field occurs in controls at about the developmental period of taste response maturation. The lack of remodeling in sodium-restricted rats may be explained by a corresponding lack of functional response development to sodium salts. These results also illustrate the specificity and extent of how early dietary manipulations shape the developing brainstem.

Objective To determine the concordance of day-6 blastocyst analysis with the day-3 fluorescence in situ hybridization (FISH) aneuploidy diagnosis. Design Retrospective study. Setting In vitro fertilization laboratory. Patient(s) Six hundred sixty embryos were included from 94 IVF/intracytoplasmic sperm injection patients undergoing preimplantation genetic diagnosis. Intervention(s) None. Main Outcome Measure(s) Single blastomeres biopsied on day 3. Aneuploidy screening for chromosomes 13, 18, 21, X, and Y were analyzed. Left-over blastocysts were reanalyzed on day 6. Result(s) Among the 660 embryos evaluated, 367 (55.6%) were euploid and 281 (42.6%) were aneuploid. Of the euploid embryos, 213 embryos were transferred, 68 were frozen on day 5, and 86 were left. All 281 aneuploid embryos were further cultured, and 55 (19.6%) progressed to blastocysts. When FISH reanalysis was performed, 33 of 55 blastocysts (60%) were confirmed aneuploid in concordance with the day-3 diagnosis. However, 22 of 55 blastocysts (40%) were determined to be euploid. In addition, 207 aneuploid embryos (73.7%) arrested before day 6, as opposed to 32 of the 86 euploid embryos (37.2%). Conclusion(s) Day-3 single-cell embryo biopsy reveals that aneuploidy can be confirmed in 60.7% of the blastocysts on reanalysis. The majority of discordance is most likely due to embryo mosaicism and possibly a limited ability to "self-correct."

Coding of gustatory information is complex and unique among sensory systems; information is received by multiple receptor populations located throughout the oral cavity and carried to a single central relay by four separate nerves. The geniculate ganglion is the location of the somata of two of these nerves, the greater superficial petrosal (GSP) and the chorda tympani (CT). The GSP innervates taste buds on the palate and the CT innervates taste buds on the anterior tongue. To obtain requisite taste response profiles of GSP neurones, we recorded neurophysiological responses to taste stimuli of individual geniculate ganglion neurones in vivo in the rat and compared them to those from the CT. GSP neurones had a distinct pattern of responding compared to CT neurones. For example, a small subset of GSP neurones had high response frequencies to sucrose stimulation, whereas no CT neurones had high response frequencies to sucrose. In contrast, NaCl elicited high response frequencies in a small subset of CT neurones and elicited moderate response frequencies in a relatively large proportion of GSP neurones. The robust whole-nerve response to sucrose in the GSP may be attributable to relatively few, narrowly tuned neurones, whereas the response to NaCl in the GSP may relate to proportionately more, widely tuned neurones. These results demonstrate the diversity in the initial stages of sensory coding for two separate gustatory nerves involved in the ingestion or rejection of taste solutions, and may have implications for central coding of gustatory quality and concentration as well as coding of information used in controlling energy, fluid and electrolyte homeostasis.

A national project to develop a future capability to separate actinides and long-lived fission products from spent fuel, to transmute them, and to dispose off the remaining waste in optimal waste forms has begun in the United States. This project is based on the Accelerator-driven Transmutation of Waste (ATW) program developed during the 1990s at Los Alamos National Laboratory, and has its technological roots in several technologies that have been developed by the multi-mission laboratories of the U.S. Department of Energy (DOE). In the Fiscal Year 1999 Energy and Water Appropriation Act, the U.S. Congress directed the DOE to study ATW and by the end of FY99 to prepare a “roadmap” for developing this technology. DOE convened a steering committee, assembled four technical working groups consisting of members from many national laboratories, and consulted with several individual international and national experts. The finished product, “A Roadmap for Developing ATW Technology – A Report to Congress,” recommends a five-year, $281 M, science-based, technical-risk-reduction program. This paper provides an overview of the U.S. Roadmap for developing ATW technology, the organization of the national ATW Project, the critical issues in subsystems and technological options, deployment scenarios, institutional challenges, and academic and international collaboration.

The effect of an automatic vehicle location (AVL) system on schedule adherence and operator behavior is studied. During two sets of 4 weeks each, one set with and one set without AVL intervention, data were collected from the Mass Transit Administration (MTA) bus system in Baltimore, Maryland. Although AVL systems have many benefits, the focus is on improvements in schedule adherence and operator behavior for off-schedule bus arrival. Although ahead-of-schedule operation generates longer waiting time, adjustments can be made if the operator is aware and willing to keep on schedule. Thus, arrival status at the next time points (TPs), after early arrival at the main TPs, and link travel time between those two TPs were carefully analyzed. As a result, an improvement in schedule adherence with AVL was demonstrated with a 99 percent confidence level. However, with MTA’s current AVL intervention, the schedule adherence and link travel time after early arrival at the previous TP did not improve significantly. Those results are explained by the link travel time distribution curves, which have two peaks by two groups of operator behavior—one enjoying congestionfree traffic and the other paying attention to schedule adherence. Without strong AVL intervention, operator behavior could not be relied on to improve schedule adherence effectively.

A roadmap has been established for development of ATW Technology. The roadmap defines a reference system along with preferred technologies, which require further development to reduce technical risk, associated deployment scenarios, and a detailed plan of necessary R&D to support implementation of this technology. The potential for international collaboration is discussed which has the potential to reduce the cost of the program. A reference ATW plant design was established to ensure consistent discussion of technical and life cycle cost issues. Over 60 years of operation, a reference ATW plant would process about 10,000 tn of spent nuclear reactor fuel. This is in comparison to the current inventory U.S. of about 40,000 tn of spent fuel and the projected inventory of about 86,000 tn of spent fuel if all currently licensed nuclear power plants run until their license expire. The reference ATW plant was used together with an assumed scenario of no new nuclear plant orders in the U.S. to generate a deployment scenario for ATW. In the R&D roadmap, key technical issues are identified, and timescales are proposed for the resolution of these issues. A key recommendation is that, in the first year of any ATW program, trade studies intended to confirm technology choices and optimization of design be conducted. These studies will then be used to define future R&D. International collaboration will be important in this endeavor.

In rat, chorda tympani nerve taste responses to Na+ salts increase between roughly 10 and 45 days of age to reach stable, mature magnitudes. Previous evidence from in vitro preparations and from taste nerve responses using Na+ channel blockers suggests that the physiological basis for this developmental increase in gustatory Na+ sensitivity is the progressive addition of functional, Na+ transduction elements (i.e., amiloride-sensitive Na+ channels) to the apical membranes of fungiform papilla taste receptor cells. To avoid potential confounding effects of pharmacological interventions and to permit quantification of aggregate Na+ channel behavior using a kinetic model, we obtained chorda tympani nerve responses to NaCl and sodium gluconate (NaGlu) during receptive field voltage clamp in rats aged from 12–14 to 60 days and older (60+ days). Significant, age-dependent increases in chorda tympani responses to these stimuli occurred as expected. Importantly, apical Na+ channel density, estimated from an apical Na+ channel kinetic model, increased monotonically with age. The maximum rate of Na+response increase occurred between postnatal days 12–14 and 29–31. In addition, estimated Na+ channel affinity increased between 12–14 and 19–23 days of age, i.e., on a time course distinct from that of the maximum rate of Na+response increase. Finally, estimates of the fraction of clamp voltage dropped across taste receptor apical membranes decreased between 19–23 and 29–31 days of age for NaCl but remained stable for NaGlu. The stimulus dependence of this change is consistent with a developmental increase in taste bud tight junctional Cl− ion permeability that lags behind the developmental increase in apical Na+ channel density. A significant, indirect anion influence on apical Na+ channel properties was present at all ages tested. This influence was evident in the higher apparent apical Na+ channel affinities obtained for NaCl relative to NaGlu. This stimulus-dependent modulation of apical Na+ channel apparent affinity relies on differences in the transepithelial potentials between NaCl and NaGlu. These originate from differences in paracellular anion permeability but act also on the driving force for Na+ through apical Na+channels. Detection of such an influence on taste depends fundamentally on the preservation of taste bud polarity and on a direct measure of sensory function, such as the response of primary afferents.

During postnatal development, a relationship is established between the size of individual taste buds and number of innervating neurons. To determine whether rearrangement of neurons that innervate taste buds establishes this relationship, we labeled single taste buds at postnatal day 10 (P10) and again at either P15, P20, or P40 with retrograde fluorescent neuronal tracers. The number of single- and double-labeled geniculate ganglion cells was counted, and the respective taste bud volumes were measured for the three groups of rats. The current study replicates findings from an earlier report demonstrating that the larger the taste bud, the more geniculate ganglion cells that innervate it. This relationship between taste bud size and number of innervating neurons is not apparent until P40, when taste bud size reaches maturity. These findings are extended here by demonstrating that the number of neurons that innervate taste buds at P10, when taste bud size is small and relatively homogeneous, predicts the size that the respective taste bud will become at maturity. Moreover, while there is some neural rearrangement of taste bud innervation from P10 to P40, rearrangement does not impact the relationship between taste bud size and innervating neurons. That is, the neurons that maintain contact with taste buds from P10 through P40 accurately predict the mature taste bud size. Therefore, the size of the mature taste bud is determined by P10 and relates to the number of sensory neurons that innervate it at that age and the number of neurons that maintain contact with it throughout the first 40 days of postnatal development. © 2000 John Wiley & Sons, Inc. J Neurobiol 43: 98–106, 2000

Dietary sodium restriction has profound effects on the development of peripheral taste function and central taste system anatomy. This study examined whether early dietary sodium restriction also affects innervation of taste buds. The number of geniculate ganglion cells that innervate single fungiform taste buds were quantified for the midregion of the tongue in two groups of rats: those fed either a low-sodium diet and those fed a sodium replete diet (control rats) from early prenatal development through adulthood. The same mean number of ganglion cells in developmentally sodium-restricted and control adult rats innervated taste buds on the midregion of the tongue. However, the characteristic relationship of the larger the taste bud, the more neurons that innervate it did not develop in sodium-restricted rats. The failure to form such a relationship in experimental rats was likely due to a substantially smaller mean taste bud volume than controls and probably not to changes in innervation. Further experiments demonstrated that the altered association between number of innervating neurons and taste bud size in restricted rats was reversible. Feeding developmentally sodium-restricted rats a sodium replete diet at adulthood resulted in an increase in taste bud size. Accordingly, the high correlation between taste bud volume and innervation was established in sodium-replete rats. Findings from the current study reveal that early dietary manipulations influence neuron–target interactions; however, the effects of dietary sodium restriction on peripheral gustatory anatomy can be completely restored, even in adult animals. © 1999 John Wiley & Sons, Inc. J Neurobiol 39: 218–226, 1999

To determine whether the innervation of taste buds changes during postnatal development, the number of geniculate ganglion cells that innervated single fungiform taste buds were quantified in the tip- and midregions of the tongue of adult and developing rats. There was substantial variation in both the size of individual taste buds and number of geniculate ganglion cells that innervated them. Importantly, taste bud morphology and innervation were highly related. Namely, the number of labeled geniculate ganglion cells that innervated a taste bud was highly correlated with the size of the taste bud (r 5 0.91, P , .0003): The larger the taste bud, the more geniculate ganglion cells that innervated it. The relationship between ganglion cell number and taste bud volume emerged during the first 40 days postnatal. Whereas there was no difference in the average number of ganglion cells that innervated individual taste buds in rats aged 10 days postnatal through adulthood, taste bud volumes increased progressively between 10 and 40 days postnatal, at which age taste bud volumes were similar to adults. The maturation of taste bud size was accompanied by the emergence of the relationship between taste bud volume and number of innervating neurons. Specifically, there was no correlation between taste bud size and number of innervating geniculate ganglion cells in 10-, 20-, or 30-day-old rats, whereas taste bud size and the number of innervating ganglion cells in 40-day-old rats were positively correlated (r 5 .80, P , .002). Therefore, the relationship between taste bud size and number of innervating ganglion cells develops over a prolonged postnatal period and is established when taste buds grow to their adult size. J. Comp. Neurol. 398:13‐24, 1998. r 1998 Wiley-Liss, Inc. Indexing terms: taste bud; geniculate ganglion; sensory afferents; fluorescent tracers; tongue

WALKER, B. R. AND D. L. HILL. Developmental sodium restriction and gustatory afferent terminal field organization in the parabrachial nucleus. Physiol Behav 64 (2) 173–178, 1998. Dietary sodium restriction instituted early in prenatal development produces physiological, anatomical, and functional changes in the gustatory system. For example, a rearrangement of the chorda tympani nerve terminal field within the nucleus of the solitary tract (NST) is observed in rats sodium restricted during development. The altered pattern of the chorda tympani nerve innervation within the nucleus of the solitary tract remains even after dietary sodium is restored in the diet at adulthood. In light of these observations, the terminal fields of second-order projections from the nucleus of the solitary tract to the parabrachial nucleus (PBn) were examined. To determine the possible rearrangements of the second-order projections, the rostral pole of the NST in control, restricted, and repleted rats was injected with the fluorescent tracer Fluoro-Ruby and the terminal fields in the parabrachial nucleus were analyzed. Results show no differences in the size or topography of the parabrachial nucleus terminal field among control, restricted, and repleted rats. These results suggest that the terminal field of second-order gustatory neurons is resistant to dietary sodium restriction during development. The apparent target-dependent effects may relate to differences in the developmental processes along the gustatory pathway.