The ventrolateral medulla of the cat mediates vestibulosympathetic reflexes

Extracellular recordings were made from 94 neurons located in the ventrolateral medulla (VLM) whose firing rate was affected by vestibular nerve (VN) stimulation; 50 of these units were in the subretrofacial (SRF) nucleus, which contains cells that make direct excitatory connections with sympathetic preganglionic neurons. The sample included 12 SRF cells which were antidromically driven from the upper thoracic spinal cord and had conduction velocities of 10 m/s or less; the effect of VN stimulation on all but one of these units was inhibition. The onset latency of the response to VN stimulation was long [20.3 +/- 3.7 (S.E.M.) ms, n = 9, for the antidromically activated neurons and 12.1 +/- 1.2 ms, n = 73, for the others], suggesting that the effects were predominantly polysynaptic. In addition, most of the spontaneously active units tested (33/36) received convergent inputs from the carotid sinus nerve (CSN), as would be expected for neurons which influence sympathetic outflow. Vestibular-elicited inhibition of SRF neurons with projections to the intermediolateral cell column could account for late, long duration inhibition of sympathetic discharges produced by labyrinth stimulation.     

I. Indices of Pain Intensity Derived From Ecological Momentary Assessments: Rationale and Stakeholder Preferences

Pain assessment that fully represents patients’ pain experiences is essential for chronic pain research and management. The traditional primary outcome measure has been a patient's average pain intensity over a time period. In this series of 3 articles, we examine whether pain assessment can be enhanced by considering additional outcome measures capturing temporal aspects of pain, such as pain maxima, duration, and variability. Ecological momentary assessment makes the assessment of such indices readily available. In this first article, we discuss the rationale for considering additional pain indices derived from ecological momentary assessment and examine which are most important to stakeholders. Patients (n = 32), clinicians (n = 20), and clinical trialists (n = 20) were interviewed about their preference rankings for Average, Worst, and Least Pain, Time in High Pain, Time in No/Low Pain, Pain Variability, and Pain Unpredictability. Each stakeholder group displayed a distinct preference hierarchy for different indices, and there were few commonalities between groups. Patients favored Worst Pain and Time in High Pain, followed by Pain Variability and Unpredictability. Trialists favored Average Pain, whereas clinicians favored Worst Pain. Results suggest that multiple temporal aspects of pain are relevant for stakeholders and should be considered when evaluating the efficacy of pain management.PerspectiveExamining which aspects of pain are most important to measure from the perspective of different stakeholders can facilitate efforts to include all relevant treatment outcomes. Our study suggests that multiple temporal aspects of pain intensity are important to stakeholders. This should be considered when evaluating the efficacy of pain management.     

Association Between Polymorphisms of the Dopamine Receptor D2 and Catechol-o-Methyl Transferase Genes and Cognitive Function

The dopaminergic neurotransmitter system of the brain is involved in working memory and other cognitive functions. Studies suggest an important role for dopamine synthesis and uptake in modulation of human cognitive processes. We studied the association between polymorphisms in the catechol-o-methyl transferase (COMT) and dopamine receptor D2 (DRD2) genes and general cognitive ability in a secondary analysis of 2091 men and women, aged 55–80 years living in Scotland. General cognitive ability ‘g’ was derived from five cognitive tests of different domains. COMT was not associated with cognitive ability in this population. The DRD2 C:C genotype of rs6277 was associated with decreased general cognitive ability ‘g’ (p = 0.003), and DRD2 rs1800497 heterozygotes had lowest mean general cognitive ability ‘g’ (p = 0.007). There was an indication of a potential interaction between the DRD2 SNPs.     

Vaginal birth after cesarean: do California hospital policies follow national guidelines?

OBJECTIVE: To review whether California hospitals are adhering to national practice guidelines with regard to vaginal birth after cesarean (VBAC). STUDY DESIGN: We performed a content analysis of the American College of Obstetricians and Gynecologists (ACOG) and American Association of Family Physicians published guidelines and identified 39 specific recommendations, which were categorized into the following 5 content areas: patient criteria, procedure, staff and resources, uterine rupture or other complications, and miscellaneous clinical issues. We evaluated individual hospital policies with regard to adherence to 34 recommendations made specifically by ACOG. RESULTS: Of the 225 surveyed hospitals, 167 (74%) allow VBAC, and 22% of these (36 of 167) provided VBAC protocols for review. Approximately 80% of protocols included < 50% of the ACOG items (median, 13.5; range, 3-27 items). The highest percent adherence was observed in the procedure and staff and resources categories, where over two thirds of study hospitals exhibited 75-100% adherence. One third of participating hospitals were less adherent (0-25%) in the categories of patient criteria, uterine rupture or other complications, and miscellaneous clinical issues. CONCLUSION: In a sample of written VBAC protocols, we found a wide range of adherence to ACOG recommendations, as evidenced by the number and type of items explicitly documented in the protocols.     

The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis

Tuberous sclerosis is an autosomal dominant trait in which the dysregulation of cellular proliferation and differentiation results in the development of hamartomatous growths in many organs. The TSC2 gene is one of two genes determining tuberous sclerosis. Inactivating germline mutations of TSC2 in patients with tuberous sclerosis and somatic loss of heterozygosity at the TSC2 locus in the associated hamartomas indicate that TSC2 functions as a tumour suppressor gene and that loss of function is critical to expression of the tuberous sclerosis phenotype. The TSC2 product, tuberin, has a region of homology with the GTPase activating protein rap1GAP and stimulates the GTPase activity of rap1a and rab5a in vitro. Here we show that the region of homology between tuberin and human rap1GAP and the murine GAP mSpa1 is more extensive than previously reported and spans approximately 160 amino acid residues encoded within exons 34-38 of the TSC2 gene. Single strand conformation polymorphism analysis of these exons in 173 unrelated patients with tuberous sclerosis and direct sequencing of variant conformers together with study of additional family members enabled characterisation of disease associated mutations in 14 cases. Missense mutations, which occurred in exons 36, 37 and 38 were identified in eight cases, four of whom shared the same recurrent change P1675L. Each of the five different missense mutations identified was shown to occur de novo in at least one sporadic case of tuberous sclerosis. The high proportion of missense mutations detected in the region of the TSC2 gene encoding the GAP-related domain supports its key role in the regulation of cellular growth.      

"Nice guys finish last": influence of mate choice on reproductive success in Long-Evans rats

The present study was designed to determine if male physiology and male reproductive behavior predict reproductive success in Long–Evans rats. Mating behavior was observed in sexually naïve, naturally cycling female rats during behavioral estrous that were given the opportunity to mate with two males simultaneously. DNA analysis of offspring born following these mating encounters was used to identify the paternity of each pup. In order to assess the effect of mate choice during these mating encounters on reproductive success, one male rat in each pair was categorized as the preferred mate if the female spent more time (> 50%) with him during the mating test of the present study. Furthermore, each male in the pairs was categorized as “attractive” or “non-attractive” by computing the number of females that preferred each male across many mating tests. Similar to results reported in Lovell et al. (2007), during 76% of these mating tests the same male rat in each pair was preferred by different female rats. Overall attractiveness of individual male rats predicted reproductive success in the present study. Interestingly, “attractive” males sired significantly FEWER pups than “non-attractive” males. Neither behavioral (e.g., latency to first sexual stimulation, number of sexual stimulations) nor physiological measures (e.g., body weight, urinary testosterone levels) of male rats predicted their reproductive success. In conclusion, the present results indicate that certain features of some males are more attractive to females, but attractive males are at a reproductive disadvantage (as measured by the number of pups sired). Although basal urinary testosterone levels did not differ between males that sired the majority of pups in a litter and males that sired few or none of the pups in a litter, aggression and/or other physiological measures of fertility (e.g., penile reflexes) may differ between males that are attractive to females and those that have a reproductive advantage.     

A prospective comparison of 'in house' and commercially prepared Earle's balanced salt solution in human in-vitro fertilization.

A prospective, randomized study was undertaken to compare the use of Earle's balanced salt solution (EBSS) prepared 'in house' with that produced commercially, in 448 cycles of therapeutic in-vitro fertilization. Outcome was assessed in terms of fertilization and cleavage rates, embryo morphology, and implantation rates following embryo transfer. The only differences that were found between the two media in any of the outcome parameters were in the number of cycles with failed fertilization (1/218 in 'in house' medium compared with 10/230 in commercially prepared medium; P = 0.0186), and in the rate at which embryos cleaved. Thus, while the median number of blastomeres per embryo was no different in the two groups at 46-49 h post insemination (three in embryos cultured in 'in-house' medium, compared with four in those cultured in commercially prepared medium; P > 0.1), the number of embryos per cycle that had cleaved to the 4-cell stage by 46-49 h post insemination was significantly greater in the Medi-Cult than in the EBSS medium (P < 0.001).