Pet collars containing tetrachlorvinphos (TCVP): evaluation of the results of torsion and on-animal release studies and implications for post-application consumer exposure and risk analysis.

Tetrachlorvinphos (TCVP) is the pesticidal active ingredient found in some flea and tick collars for dogs and cats. Recent studies sponsored by The Hartz Mountain Corporation, confirm the safety of TCVP as an active ingredient in pet collars. Based upon data from these new studies and results previously relied upon by the U.S. Environmental Protection Agency, the following conclusions have been made: Torsion study data clearly indicate that approximately 93% of released formulation from TCVP containing pet collars is in a liquid phase immediately following activation.Further, even more relevant to human health risk analysis associated with post-application exposures, in vivo data from dogs wearing TCVP pet collars definitively document that TCVP dust released from the collar is rapidly absorbed into the sebum. The maximum ratio of dust to liquid was 0.023% dust to 99.977% liquid.In vivo fur data provide scientific evidence confirming that the mechanism of dissemination of TCVP from pet collars is as a liquid suspended or dissolved in the animal's sebum, even though it may be released from the collar as a solid. Thus, potential post-application exposure to TCVP, including immediately following collar placement, is almost entirely to a liquid phase.Based upon EPA's refined and conservative "untrimmed" collar risk assessment, post-application incidental oral hand-to-mouth activity by children aged 1 to <2 years of age results in margins of exposure significantly greater than the level of concern of 1000, and therefore do not present unreasonable health risk.

Mendel: From genes to genome.

Two hundred years after the birth of Gregor Mendel, it is an appropriate time to reflect on recent developments in the discipline of genetics, particularly advances relating to the prescient friar's model species, the garden pea (Pisum sativum L.). Mendel's study of seven characteristics established the laws of segregation and independent assortment. The genes underlying four of Mendel's loci (A, LE, I, and R) have been characterized at the molecular level for over a decade. However, the three remaining genes, influencing pod color (GP), pod form (V/P), and the position of flowers (FA/FAS), have remained elusive for a variety of reasons, including a lack of detail regarding the loci with which Mendel worked. Here, we discuss potential candidate genes for these characteristics, in light of recent advances in the genetic resources for pea. These advances, including the pea genome sequence and reverse-genetics techniques, have revitalized pea as an excellent model species for physiological-genetic studies. We also discuss the issues that have been raised with Mendel's results, such as the recent controversy regarding the discrete nature of the characters that Mendel chose and the perceived overly-good fit of his segregations to his hypotheses. We also consider the relevance of these controversies to his lasting contribution. Finally, we discuss the use of Mendel's classical results to teach and enthuse future generations of geneticists, not only regarding the core principles of the discipline, but also its history and the role of hypothesis testing.

Estimated Dermal Penetration of Tetrachlorvinphos (TCVP) in Humans Based on In Silico Modeling and In Vitro and In Vivo Data.

Tetrachlorvinphos (TCVP) is the pesticidal active ingredient in some collars for dogs and cats. The objective of this study was to provide a refined estimate of dermal penetration of TCVP in humans using in silico predictions as well as in vitro and in vivo data. The in vivo dermal absorption of TCVP was previously studied in the rat and shown to be saturable, ranging from 21.7% (10 µg/cm2) down to 3% (1000 µg/cm2) Subsequent in silico predictions were conducted for rats and humans to provide initial evaluations of species and dose-dependent differences in dermal absorption. A definitive comparison of TCVP systemic exposure in rat and human following dermal application was then conducted via a standard in vitro assay. TCVP dose levels of 10, 100, or 1000 µg/cm2 were applied to excised rat and human skin mounted in flow-through diffusion cells. The vehicle was 1% hydroxypropylmethylcellulose (HPMC) in water. An additional 5 µg/cm2 dose was applied to excised human skin only. The in vitro dermal absorption of TCVP was also assessed from artificial sebum at dose levels of 5, 10, or 100 µg/cm2 applied to human skin only. Utilizing the so-called triple pack approach with in vitro and in vivo rat data and in vitro human data, dermal absorption for TCVP was calculated for humans. In silico modeling indicated absorption of TCVP through human skin might be 3- to 4- fold lower than rat skin at all application levels, with a maximum dermal absorption of 9.6% at the lowest exposure of 10 µg/cm2, down to 0.1% at 1000 µg/cm2. Similar species differences were also found in the definitive in vitro absorption assays. Modeling overestimated TCVP human dermal absorption (9.6%) as compared to excised human skin results (1.7%) for the HPMC vehicle at the lowest exposure (10 µg/cm2), with better agreement at the higher exposures. Conversely, modeling accurately predicted rat dermal absorption (27.9%) as compared to in vivo rat results (21.7%) at the lowest exposure in HPMC, with diminished agreement at the higher exposures. As a first approximation, in silico estimates of dermal absorption are useful; however, these tend to be more variable than in vitro or in vivo measurements. TCVP dermal penetration measured in vitro was lower in 1% HPMC vehicle as compared to artificial sebum. For the 1% HPMC vehicle, in vitro rat dermal absorption was similar to data obtained for in vivo rats, giving confidence in the triple pack approach. In consideration of the triple pack approach, estimated human dermal absorption from 1% HPMC was ≤2%. Based upon excised human skin determinations directly, estimated human dermal absorption of TCVP from artificial sebum was ≤7%.

IN.PACT AV Access Randomized Trial: 12-Month Clinical Results Demonstrating the Sustained Treatment Effect of Drug-Coated Balloons.

PURPOSE: To present the 12-month outcomes of the IN.PACT AV Access Study, a prospective, single-blind trial enrolling participants with obstructive de novo or restenotic native upper extremity arteriovenous dialysis fistula lesions treated with a drug-coated balloon (DCB) or percutaneous transluminal angioplasty (PTA). MATERIALS AND METHODS: After successful high-pressure PTA, participants at 29 international sites were randomized 1:1 to treatment with an IN.PACT AV DCB (n = 170) or standard uncoated PTA (n = 160). Outcomes at 12 months include target lesion primary patency (TLPP), defined as freedom from clinically driven target lesion revascularization or access circuit thrombosis; access circuit primary patency; number of reinterventions; and adverse events involving the access circuit. RESULTS: At 12 months, TLPP was 63.8% (90/141) in the DCB group compared with 43.6% (61/140) in the PTA group (P < .001). The total number of reinterventions required to maintain TLPP through 360 days was 93 in the DCB group and 144 in the PTA group, with a 35.4% reduction in reinterventions when DCB was used. Access circuit thrombosis occurred in 2.9% (4/138) of the participants in the DCB group and in 6.2% (8/129) of those in the PTA group (P = .19). Time to TLPP was assessed using a multivariable analysis to identify the factors associated with loss of patency. The treatment device was the independent predictor with the largest effect, with a hazard ratio of 0.42 (95% confidence interval, 0.29-0.60; P < .001). CONCLUSIONS: TLPP was statistically significantly higher with DCBs than with standard PTA at 12 months, demonstrating the sustained and superior effectiveness of this device for the treatment of dysfunctional arteriovenous dialysis fistulae.

Declining yet persistent use of traditional contraceptive methods in low- and middle-income countries.

Traditional contraceptive methods are used by 55 million women in developing countries. This study analysed over 80 national surveys to compare traditional with modern method users, by type, region, socio-demographic characteristics, strength of family planning programmes and discontinuation rates. The advance of modern methods has greatly reduced the share held by traditional methods, but the actual prevalence of their use has declined little. Young, sexually active unmarried women use traditional contraception much more than their married counterparts. Discontinuation rates are somewhat lower for traditional methods than for the resupply methods of the pill, injectable and condom; among users of all of these methods, more than a quarter stop use in the first year to switch to alternative methods. Traditional method use is firmly entrenched in many countries, as the initial method tried, a bridge method to modern contraception and even the primary method where other methods are not easily available.

Trehalose 6-phosphate promotes seed filling by activating auxin biosynthesis.

Plants undergo several developmental transitions during their life cycle. One of these, the differentiation of the young embryo from a meristem-like structure into a highly specialized storage organ, is believed to be controlled by local connections between sugars and hormonal response systems. However, we know little about the regulatory networks underpinning the sugar-hormone interactions in developing seeds. By modulating the trehalose 6-phosphate (T6P) content in growing embryos of garden pea (Pisum sativum), we investigate here the role of this signaling sugar during the seed-filling process. Seeds deficient in T6P are compromised in size and starch production, resembling the wrinkled seeds studied by Gregor Mendel. We show also that T6P exerts these effects by stimulating the biosynthesis of the pivotal plant hormone, auxin. We found that T6P promotes the expression of the auxin biosynthesis gene TRYPTOPHAN AMINOTRANSFERASE RELATED2 (TAR2), and the resulting effect on auxin concentrations is required to mediate the T6P-induced activation of storage processes. Our results suggest that auxin acts downstream of T6P to facilitate seed filling, thereby providing a salient example of how a metabolic signal governs the hormonal control of an integral phase transition in a crop plant.

Once daily combined inhaled steroid and ultra long-acting bronchodilator prescribing in pediatric asthma: a dual Center retrospective cohort study.

OBJECTIVE: A high proportion of children and adolescents who have "difficult" or therapy-resistant asthma, are found to have poor adherence to maintenance therapies. Such individuals are thus difficult asthmatics (for reasons of poor adherence) rather than being young people with true difficult asthma. In our centers, once daily ICS/ULABA (Relvar™) is considered if there is an increase in reported interval symptoms, asthma attacks requiring hospital attendance or rescue oral prednisolone, or persistently low lung function despite reported regular use of a twice daily ICS/LABA preparation. In the majority of these young people, a clinical history of overt non-adherence or a clinical suspicion of covert non-adherence will be noted. METHODS: The aim of our retrospective cohort study was to assess the clinical effectiveness of Relvar™ in a selected adolescent asthma population. RESULTS: In a pre-selected group of adolescents with likely poor prior adherence to inhaled therapies, a change to Relvar™ (once daily combined ICS/ULABA) led to improvements in asthma control, as assessed by ED attendances and oral steroid burden. CONCLUSIONS: A prospective study to verify these findings and also explore the effects on quality of life, asthma control, and adherence is warranted.

The subscapularis-sparing windowed anterior technique for total shoulder arthroplasty.

BACKGROUND: Traditionally, total shoulder arthroplasty (TSA) involves detaching the subscapularis tendon through either tenotomy or lesser tuberosity osteotomy. A subscapularis-sparing approach avoids detachment but may make re-creation of the anatomy more difficult because of limited exposure. The primary aim of this study was to evaluate the ability to re-create the proximal humeral geometry and assess for osteophyte removal with this technique. The secondary aim was to assess for complications or an inability to complete the procedure with this technique. METHODS: We performed a retrospective review of a consecutive series of 47 patients (100% with osteoarthritis; 59% Walch type A and 41% Walch type B; 50% male and 50% female patients; and average body mass index, 28.21 ± 4.6) who underwent the subscapularis-sparing windowed anterior technique for TSA. The ability to reconstruct the proximal humeral geometry and remove the inferior osteophytes was assessed by 2 independent observers using the center-of-rotation difference (ΔCOR) between the native and prosthetic humeral heads. The ability to complete the procedure was recorded, and a chart review was performed to assess for complications. RESULTS: The procedure was successfully completed in 44 of the 47 patients. Radiographic review demonstrated an average ΔCOR of 2.28 mm (range, 0.2-6.05 mm; intraclass correlation coefficient, 0.971), below the previously reported acceptable ΔCOR of 3 mm. The ΔCOR was >3 mm in 31.8% of patients (14 of 44; 8 Walch type A and 6 Walch type B; 9 male and 5 female patients). There was no difference in ΔCOR based on Walch type (P = .824). Male patients on average showed a higher ΔCOR (2.62 mm) than female patients (1.94 mm) (P = .099) and more commonly had a ΔCOR > 3 mm (P = .195). Body mass index was not significantly correlated with ΔCOR (r = 0.077, P = .619). For all cases in which the ΔCOR was >3 mm, the prosthetic humeral head was undersized. Osteophytes were successfully removed in 75% of cases (33 of 44) and had no effect on average ΔCOR (P = .468). No revisions or mechanical failures in the early postoperative period were identified in the treatment group of 44 patients (range, 3-15 months). In the group with unsuccessful treatment, there was 1 case of infection treated with 1-stage revision reverse TSA. DISCUSSION: The subscapularis-sparing windowed anterior technique is an effective approach to TSA that allows for early unrestricted motion. Over 90% of cases can be completed using this technique. Radiographic analysis demonstrated that this approach can be used successfully without compromising anatomic reconstruction of the proximal humerus. Further study is necessary to identify patient factors that would favor a traditional deltopectoral approach and to assess the functional outcomes of this technique.

A Systematic Review and Meta-analysis of Clinical Trials of Neuraxial, Intravenous, and Inhalational Anesthesia for External Cephalic Version.

BACKGROUND: External cephalic version (ECV) is a frequently performed obstetric procedure for fetal breech presentation to avoid cesarean delivery. Neuraxial, intravenous, and inhalational anesthetic techniques have been studied to reduce maternal discomfort caused by the forceful manipulation. This study compares the effects of these anesthetic techniques on ECV and incidence of cesarean delivery. METHODS: We conducted a comprehensive literature search for published randomized controlled trials (RCTs) or well-conducted quasi-randomized trials of ECV performed either without anesthesia or under neuraxial, intravenous, or inhalational anesthesia. Pairwise random-effects meta-analyses and network meta-analyses were performed to compare and rank the perinatal outcomes of the 3 anesthetic interventions and no anesthesia control, including the rate of successful version, cesarean delivery, maternal hypotension, nonreassuring fetal response, and adequacy of maternal pain control/satisfaction. RESULTS: Eighteen RCTs and 1 quasi-randomized trial involving a total of 2296 term parturients with a noncephalic presenting singleton fetus were included. ECV under neuraxial anesthesia had significantly higher odds of successful fetal version compared to control (odds ratio [OR] = 2.59; 95% confidence interval [CI], 1.88-3.57), compared to intravenous anesthesia (OR = 2.08; 95% CI, 1.36-3.16), and compared to inhalational anesthesia (OR = 2.30; 95% CI, 1.33-4.00). No association was found between anesthesia interventions and rate of cesarean delivery. Neuraxial anesthesia was associated with higher odds of maternal hypotension (OR = 9.33; 95% CI, 3.14-27.68). Intravenous anesthesia was associated with significantly lower odds of nonreassuring fetal response compared to control (OR = 0.36; 95% CI, 0.16-0.82). Patients received neuraxial anesthesia reported significantly lower visual analog scale (VAS) of procedure-related pain (standardized mean difference [SMD] = -1.61; 95% CI, -1.92 to -1.31). The VAS scores of pain were also significantly lower with intravenous (SMD = -1.61; 95% CI, -1.92 to -1.31) and inhalational (SMD = -1.19; 95% CI, -1.58 to -0.8) anesthesia. The VAS of patient satisfaction was significantly higher with intravenous anesthesia (SMD = 1.53; 95% CI, 0.64-2.43). CONCLUSIONS: Compared to control, ECV with neuraxial anesthesia had a significantly higher successful rate; however, the odds of maternal hypotension increased significantly. All anesthesia interventions provided significant reduction of procedure-related pain. Intravenous anesthesia had significantly higher score in patient satisfaction and lower odds of nonreassuring fetal response. No evidence indicated that anesthesia interventions were associated with significant decrease in the incidence of cesarean delivery compared to control.

Reproductive efficiency in the developing world.

This study proposes a measure of reproductive losses starting from conception to age 15 as an assessment of childbearing 'efficiency'. It is suggested that losses are due to miscarriages, abortions, stillbirths and deaths to age 15. Data were drawn from various sources for seven regions embracing 129 developing countries. Mortality is an important loss in severely disadvantaged regions, especially in sub-Saharan Africa, but the abortion rates are lower there. This is reversed in the more advanced regions, where mortality is low but abortion rates are higher. Total losses numerically depend upon the rates in combination with the numbers of conceptions. The general 'efficiency' in moving from conception to a surviving child aged 15 was estimated. The abortion component of wastage has apparently not improved over time, but the mortality component has done so. Abortion rates are found to drive reproductive efficiency downwards; but efficiency is positively correlated with contraceptive use once abortion is controlled for. This implies that as efficiency is improved more couples gain confidence to turn to contraceptive use to avoid unplanned pregnancies and births.

Comparing Diagnosis of Fetal Growth Restriction and the Potential Impact on Management and Outcomes Using Different Growth Curves.

OBJECTIVES: The diagnosis of fetal growth restriction (FGR) is managed with close fetal surveillance and often requires iatrogenic delivery, as there is an associated increased risk of fetal demise. However, there is no standard reference for fetal growth. We sought to compare the intrauterine growth curve of Hadlock et al (Radiology 1991; 181:129-133) to other known growth curves to determine which one best identifies fetuses at risk without overburdening the patient and health care system with unnecessary intervention. METHODS: We retrospectively reviewed charts of singleton euploid pregnancies with a diagnosis of FGR (per Hadlock) at a tertiary care center from June 2014 to May 2015. We applied the estimated fetal weights from ultrasound at diagnosis of FGR to 4 population-based growth curves by Brenner et al (Am J Obstet Gynecol 1976; 126:555-564), Williams et al (Obstet Gynecol 1982; 59:624-632), Alexander et al (Obstet Gynecol 1996; 87:163-168), and Duryea et al (Obstet Gynecol 2014; 124:16-22) and reassessed the incidence of FGR using each curve. We reviewed pregnancy demographics, risk factors, pregnancy management, and outcomes of FGR cohorts on each curve to evaluate whether poor outcomes may be missed or interventions may be avoided using the population-based curves. A sensitivity analysis was also done to see how well each curve predicted small-for-gestational-age birth weights. RESULTS: Applying any of the population-based growth curves decreased the number of FGR diagnoses, iatrogenic deliveries, and primary cesarean deliveries. Brenner's growth curve identified the least number of FGR diagnoses at 22 of the 107 identified by Hadlock. Williams' growth curve performed best in the sensitivity analysis with sensitivity of 99% and specificity of 97%. A small number of patients with absent/reversed end-diastolic flow would have been missed by applying the population curves. CONCLUSIONS: Applying the population-based growth curves instead of Hadlock's for diagnosis of FGR decreases its incidence, therefore decreasing the number of visits for ultrasound and fetal surveillance and the number of iatrogenic deliveries. However, using these curves could miss a few fetuses with increased risk of fetal demise.

Linking Auxin with Photosynthetic Rate via Leaf Venation.

Land plants lose vast quantities of water to the atmosphere during photosynthetic gas exchange. In angiosperms, a complex network of veins irrigates the leaf, and it is widely held that the density and placement of these veins determines maximum leaf hydraulic capacity and thus maximum photosynthetic rate. This theory is largely based on interspecific comparisons and has never been tested using vein mutants to examine the specific impact of leaf vein morphology on plant water relations. Here we characterize mutants at the Crispoid (Crd) locus in pea (Pisum sativum), which have altered auxin homeostasis and activity in developing leaves, as well as reduced leaf vein density and aberrant placement of free-ending veinlets. This altered vein phenotype in crd mutant plants results in a significant reduction in leaf hydraulic conductance and leaf gas exchange. We find Crispoid to be a member of the YUCCA family of auxin biosynthetic genes. Our results link auxin biosynthesis with maximum photosynthetic rate through leaf venation and substantiate the theory that an increase in the density of leaf veins coupled with their efficient placement can drive increases in leaf photosynthetic capacity.

Kinetics methods for clinical epidemiology problems.

Calculating the probability of each possible outcome for a patient at any time in the future is currently possible only in the simplest cases: short-term prediction in acute diseases of otherwise healthy persons. This problem is to some extent analogous to predicting the concentrations of species in a reactor when knowing initial concentrations and after examining reaction rates at the individual molecule level. The existing theoretical framework behind predicting contagion and the immediate outcome of acute diseases in previously healthy individuals is largely analogous to deterministic kinetics of chemical systems consisting of one or a few reactions. We show that current statistical models commonly used in chronic disease epidemiology correspond to simple stochastic treatment of single reaction systems. The general problem corresponds to stochastic kinetics of complex reaction systems. We attempt to formulate epidemiologic problems related to chronic diseases in chemical kinetics terms. We review methods that may be adapted for use in epidemiology. We show that some reactions cannot fit into the mass-action law paradigm and solutions to these systems would frequently exhibit an antiportfolio effect. We provide a complete example application of stochastic kinetics modeling for a deductive meta-analysis of two papers on atrial fibrillation incidence, prevalence, and mortality.

Evidence that auxin is required for normal seed size and starch synthesis in pea.

In recent years the biosynthesis of auxin has been clarified with the aid of mutations in auxin biosynthesis genes. However, we know little about the effects of these mutations on the seed-filling stage of seed development. Here we investigate a key auxin biosynthesis mutation of the garden pea, which results in auxin deficiency in developing seeds. We exploit the large seed size of this model species, which facilitates the measurement of compounds in individual seeds. The mutation results in small seeds with reduced starch content and a wrinkled phenotype at the dry stage. The phenotypic effects of the mutation were fully reversed by introduction of the wild-type gene as a transgene, and partially reversed by auxin application. The results indicate that auxin is required for normal seed size and starch accumulation in pea, an important grain legume crop.

Auxin Biosynthesis: Are the Indole-3-Acetic Acid and Phenylacetic Acid Biosynthesis Pathways Mirror Images?

The biosynthesis of the main auxin in plants (indole-3-acetic acid [IAA]) has been elucidated recently and is thought to involve the sequential conversion of Trp to indole-3-pyruvic acid to IAA However, the pathway leading to a less well studied auxin, phenylacetic acid (PAA), remains unclear. Here, we present evidence from metabolism experiments that PAA is synthesized from the amino acid Phe, via phenylpyruvate. In pea (Pisum sativum), the reverse reaction, phenylpyruvate to Phe, is also demonstrated. However, despite similarities between the pathways leading to IAA and PAA, evidence from mutants in pea and maize (Zea mays) indicate that IAA biosynthetic enzymes are not the main enzymes for PAA biosynthesis. Instead, we identified a putative aromatic aminotransferase (PsArAT) from pea that may function in the PAA synthesis pathway.

Role of intravascular ultrasound imaging during endovascular interventions of failing hemodialysis access grafts.

BACKGROUND: Arteriovenous (AV) access graft complications represent a serious complication in patients undergoing hemodialysis. Angiography is one method of visualizing them. However, angiography is not always an effective means of detecting lesions that occur in this context. Intravascular ultrasound (IVUS) is an adjunct modality used to identify stenoses responsible for failing access by identifying multiple stenoses, including those that are most severe. The purpose of this study was to define the value of IVUS in patients with failing AV access grafts by comparing digital subtraction angiography (DSA) alone with DSA followed by IVUS. METHODS: This was a single-center randomized study comparing IVUS with DSA in patients with failing hemodialysis access grafts. It consisted of 100 randomized hemodialysis patients presenting with failing AV access who were being considered for endovascular intervention. Interventions in the control group were guided by DSA alone, whereas interventions in the test group were guided by DSA followed by IVUS. Patients were observed for 6 months after intervention. The primary end point was the time in days to AV access graft failure after the index intervention, expressed as median and interquartile range. Secondary analyses included influence of DSA and IVUS on index procedure decision-making and percentage of patients with AV access graft reinterventions or discontinuation through 3 and 6 months. RESULTS: Median time to first AV graft reintervention or discontinuation was 61 days in the test group and 30 days in the control group (P = .16), with analysis limited to patients who experienced reintervention or discontinuation (n = 59). IVUS resulted in a change in treatment plan in 76% (44/58) of patients, with no treatment change after IVUS in 24% (14/58) of patients. At 6 months, approximately 35% of patients in both the control and test groups remained free from reinterventions (P = .88). At 6 months, approximately 75% of patients in the control group and 80% of patients in the test group remained free from AV graft discontinuation or abandonment (P = .45). CONCLUSIONS: This pilot study suggests that addition of IVUS to standard angiography during endovascular interventions of failing hemodialysis access grafts holds potential to extend the time to the first reintervention. The data support the design and execution of an adequately powered randomized trial with longer follow-up to reliably discern the clinical benefit of IVUS as an addition to standard angiography in the setting of failing AV access grafts.

EARLY FLOWERING3 Regulates Flowering in Spring Barley by Mediating Gibberellin Production and FLOWERING LOCUS T Expression.

EARLY FLOWERING3 (ELF3) is a circadian clock gene that contributes to photoperiod-dependent flowering in plants, with loss-of-function mutants in barley (Hordeum vulgare), legumes, and Arabidopsis thaliana flowering early under noninductive short-day (SD) photoperiods. The barley elf3 mutant displays increased expression of FLOWERING LOCUS T1 (FT1); however, it remains unclear whether this is the only factor responsible for the early flowering phenotype. We show that the early flowering and vegetative growth phenotypes of the barley elf3 mutant are strongly dependent on gibberellin (GA) biosynthesis. Expression of the central GA biosynthesis gene, GA20oxidase2, and production of the bioactive GA, GA1, were significantly increased in elf3 leaves under SDs, relative to the wild type. Inhibition of GA biosynthesis suppressed the early flowering of elf3 under SDs independently of FT1 and was associated with altered expression of floral identity genes at the developing apex. GA is also required for normal flowering of spring barley under inductive photoperiods, with chemical and genetic attenuation of the GA biosynthesis and signaling pathways suppressing inflorescence development under long-day conditions. These findings illustrate that GA is an important floral promoting signal in barley and that ELF3 suppresses flowering under noninductive photoperiods by blocking GA production and FT1 expression.

Granular Cell Tumor Within an Ovarian Mature Cystic Teratoma: Report of a Unique Case and Review of the Literature.

Granular cell tumors involving the female reproductive tract are rare, with only a small number of cases described. Of the reported cases, none are documented within an ovarian mature cystic teratoma (MCT). This report documents a case of a granular cell tumor, incidentally discovered within an ovarian MCT in a 50-yr-old woman undergoing a supracervical hysterectomy and left salpingo-oophorectomy. Although malignant transformation and other secondary ovarian neoplasms in MCT have been well documented, synchronous nonovarian benign neoplasms are reported much less frequently. The histogenesis of secondary tumors arising in MCT is incompletely understood, and the current case provides additional insight, especially pertaining to schwannian and neuroectodermal tumors arising in this setting. The current case, to the best of our knowledge, represents the first report of a granular cell tumor involving a mature teratoma of any site, with the diagnosis being supported by morphologic and immunohistochemical staining characteristics.