The longitudinal loss of islet autoantibody responses from diagnosis of type 1 diabetes occurs progressively over follow-up and is determined by low autoantibody titres, early-onset, and genetic variants.

The clinical usefulness of post-diagnosis islet autoantibody levels is unclear and factors that drive autoantibody persistence are poorly defined in type 1 diabetes (T1D). Our aim was to characterise the longitudinal loss of islet autoantibody responses after diagnosis in a large, prospectively sampled UK cohort. Participants with T1D [n = 577] providing a diagnosis sample [range -1.0 to 2.0 years] and at least one post-diagnosis sample (<32.0 years) were tested for autoantibodies to glutamate decarboxylase 65 (GADA), islet antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A). Select HLA and non-HLA SNPs were considered. Non-genetic and genetic factors were assessed by multivariable logistic regression models for autoantibody positivity at initial sampling and autoantibody loss at final sampling. For GADA, IA-2A, and ZnT8A, 70.8%, 76.8%, and 40.1%, respectively, remained positive at the final sampling. Non-genetic predictors of autoantibody loss were low baseline autoantibody titres (P < 0.0001), longer diabetes duration (P < 0.0001), and age-at-onset under 8 years (P < 0.01--0.05). Adjusting for non-genetic covariates, GADA loss was associated with low-risk HLA class II genotypes (P = 0.005), and SNPs associated with autoimmunity RELA/11q13 (P = 0.017), LPP/3q28 (P = 0.004), and negatively with IFIH1/2q24 (P = 0.018). IA-2A loss was not associated with genetic factors independent of other covariates, while ZnT8A loss was associated with the presence of HLA A*24 (P = 0.019) and weakly negatively with RELA/11q13 (P = 0.049). The largest longitudinal study of islet autoantibody responses from diagnosis of T1D shows that autoantibody loss is heterogeneous and influenced by low titres at onset, longer duration, earlier age-at-onset, and genetic variants. These data may inform clinical trials where post-diagnosis participants are recruited.

Cancer risk in children born after donor ART.

STUDY QUESTION: Do children born after donor ART have an increased risk of developing childhood cancer in comparison to the general population? SUMMARY ANSWER: This study showed no overall increased risk of childhood cancer in individuals born after donor ART. WHAT IS KNOWN ALREADY: Most large population-based studies have shown no increase in overall childhood cancer incidence after non-donor ART; however, other studies have suggested small increased risks in specific cancer types, including haematological cancers. Cancer risk specifically in children born after donor ART has not been investigated to date. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study utilized record linkage to determine the outcome status of all children born in Great Britain (1992-2008) after donor ART. The cohort included 12 137 members who contributed 95 389 person-years of follow-up (average follow-up 7.86 years). PARTICIPANTS/MATERIALS, SETTING, METHODS: Records of all children born in Great Britain (England, Wales, Scotland) after all forms of donor ART (1992-2008) were linked to the UK National Registry of Childhood Tumours (NRCT) to determine the number who subsequently developed cancer by 15 years of age, by the end of 2008. Rates of overall and type specific cancer (selected a priori) were compared with age, sex and calendar year standardized population-based rates, stratifying for potential mediating/moderating factors including sex, age at diagnosis, birth weight, multiple births, maternal previous live births, assisted conception type and fresh/ cryopreserved cycles. MAIN RESULTS AND THE ROLE OF CHANCE: In our cohort of 12 137 children born after donor ART (52% male, 55% singleton births), no overall increased risk of cancer was identified. There were 12 cancers detected compared to 14.4 expected (standardized incidence ratio (SIR) 0.83; 95% CI 0.43-1.45; P = 0.50). A small, significant increased risk of hepatoblastoma was found, but the numbers and absolute risks were small (<5 cases observed; SIR 10.28; 95% CI 1.25-37.14; P < 0.05). This increased hepatoblastoma risk was associated with low birthweight. LIMITATIONS REASONS FOR CAUTION: Although this study includes a large number of children born after donor ART, the rarity of specific diagnostic subgroups of childhood cancer results in few cases and therefore wide CIs for such outcomes. As this is an observational study, it is not possible to adjust for all potential confounders; we have instead used stratification to explore potential moderating and mediating factors, where data were available. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to investigate cancer risk in children born after donor ART. Although based on small numbers, results are reassuring for families and clinicians. The small but significant increased risk of hepatoblastoma detected was associated with low birthweight, a known risk factor for this tumour type. It should be emphasized that the absolute risks are very small. However, on-going investigation with a longer follow-up is needed. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by Cancer Research UK (C36038/A12535) and the National Institute for Health Research (405526) and supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. The work of the Childhood Cancer Research Group (CCRG) was supported by the charity CHILDREN with CANCER UK, the National Cancer Intelligence Network, the Scottish Government and the Department of Health for England and Wales. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Dietary shifts affect the gastrointestinal microflora of the giant panda (Ailuropoda melanoleuca).

Giant pandas exhibit seasonal changes in bamboo plant part preference. The influences on the gastrointestinal tracts (GIT) microbial populations were evaluated during a 14-month period for a pair of adult male and female giant pandas housed at the Memphis Zoo using traditional culturing methods to enumerate eight bacterial groups (total anaerobes, total aerobes (TAR), streptococci (STR), total enterics, Escherichia coli, Bacteroides spp., lactobacilli and Clostridium spp.). Both the male and female pandas altered bamboo consumption behaviours, with a sharp decrease in leaf preference in April 2010 and returning to high levels of leaf preference from June to October, corresponding to significant shifts in the densities of TAR, STR, and lactobacilli and Bacteroides spp. These findings indicate seasonal changes in food preference affect the assemblages of microbial populations within the GIT of the giant panda and contribute to a better understanding of the importance of bamboo in this species' foraging strategy.

Recovering an endangered frog species through integrative reproductive technologies.

The establishment and management of ex situ breeding and assurance populations around the globe are meant to provide short-term solutions to the formidable loss of amphibian diversity presently occurring. Large multi-scaled facilities, such as zoos and aquariums, can provide the infrastructure to safeguard species and populations. However, often even large, economically viable facilities lack the knowledge to efficiently cater to the plethora of environmentally controlled physiological strategies that amphibians possess. Anurans present a class of amphibians that have often been viewed as easy to maintain ex situ. However, while adult survival may be relatively successful it is rarely accompanied by good reproductive output, health, and fitness. Even more conspicuous is the low survivorship of offspring produced ex situ once they are translocated back into the wild. The mountain yellow-legged frog (R. muscosa) ex situ breeding program EBP is a prime example of the challenges that amphibians EBPs face. Although more research is needed, the R. muscosa program has increased reproductive output and health of its colony by incorporating reproductive technologies and strategic genetic management in conjunction with a greater understanding of the species' natural history, to produce and translocate viable animals each year. This paper highlights the EBPs past decade of research featuring the program's contribution to building empirical, multidisciplinary approaches that boost the robustness of an endangered species, by safeguarding existing genetic diversity and maximizing fitness and survival outcomes.

Thymic B lymphocyte clones from patients with myasthenia gravis secrete monoclonal striational autoantibodies reacting with myosin, alpha actinin, or actin.

Striational autoantibodies (StrAb), which react with elements of skeletal muscle cross-striations, occur frequently in patients with thymoma associated with myasthenia gravis (MG). Dissociated thymic lymphocytes from 22 of 72 MG patients secreted StrAb when cultured with PWM. A high yield of EBV-transformed B cell lines was established from thymus, thymoma, and peripheral blood of seven patients with MG, but clones secreting StrAb arose only from the three patients who had StrAb in their sera. The monoclonal StrAb bound to A bands or I bands in skeletal muscle of human, rat, and frog. One bound to mitochondria in addition to myofibrillar I bands. None bound to nuclei, smooth muscle, or gastric mucosal cells. In immunoblot analyses and ELISAs the monoclonal StrAb bound to muscle and nonmuscle isotypes of myosin, alpha actinin, and/or actin. All bound to contractile proteins common to thymus and muscle, and one selectively immunostained epithelial cells of the thymic medulla. From these antigenic specificities we suggest that StrAb might arise as an immune response directed against the cytoskeletal anchoring proteins associated with nicotinic acetylcholine receptors in thymic epithelial cells undergoing neoplastic transformation to thymoma.

SmgGDS is up-regulated in prostate carcinoma and promotes tumour phenotypes in prostate cancer cells.

SmgGDS is a guanine nucleotide exchange factor with the unique ability to activate multiple small GTPases, implicating it in cancer development and progression. Here, we investigated the role of SmgGDS in prostate cancer by studying the expression of SmgGDS in benign and malignant prostatic tissues. We also probed SmgGDS function in three prostate carcinoma cell lines using small interfering RNA (siRNA). Immunohistochemical analysis revealed that SmgGDS levels were elevated in prostatic intraepithelial neoplasia (PIN), prostate carcinoma, and metastatic prostate carcinoma. In addition, expression of SmgGDS positively correlated with that of cyclooxygenase-2 (COX-2), a protein believed to promote the development of prostate carcinoma. Reduction of SmgGDS expression in prostate carcinoma cells inhibited proliferation and migration, irrespective of androgen receptor status. These effects were accompanied by a reduction in COX-2 expression and in activity of NF-kappaB, a known regulator of COX-2. Taken together, these findings suggest that SmgGDS promotes the development and progression of prostate cancer, possibly associated with NF-kappaB-dependent up-regulation of COX-2.

[Dietary fiber and nutritional support in pediatrics: current understanding].

The article summarizes the materials on the use of dietary fiber (DF) in the diet of children of different ages. According to the few studies that DF used in children's diets, play an important role in the prevention and treatment of obesity and in lowering serum cholesterol, which reduces the risk of children of cardiovascular disease. Given that children and adolescents consume food insufficient number of DF should be encouraged to increase in baby food for their consumption at the expense of fruit, vegetables and products prepared from cereals. A number of recommendations on the level of consumption of DF children and adolescents of all ages.

Influence of delivery system on the efficacy of low concentrations of hydrogen peroxide in the disinfection of common healthcare-associated infection pathogens.

INTRODUCTION: The ability of healthcare-associated infection pathogens to survive on environmental surfaces is well known. Disinfection is employed to reduce or remove these pathogens but disinfection failures still occur. One method with the potential to improve disinfection efficacy is whole-room disinfection with hydrogen peroxide (H2O2). AIM: To determine the influence of delivery system on the efficacy of low-concentration H2O2 on common healthcare-associated infection pathogens. METHODS: SanoStatic (electrostatic spray) was compared with SanoFog (fogging) in terms of performance for delivery of 5% H2O2 and trace silver ions for disinfection. The bacterial test challenges were vancomycin-resistant Enterobacterales (VRE), extended-spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae (ESBLK), carbapenemase-producing Enterobacterales (CPE), meticillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile spores, Bacillus atropheus and Geobacillus stearothermophilus commercial spore strips. FINDINGS: SanoFog and SanoStatic were effective when tested under the conditions of experimentation reported here. For VRE, ESBLK, CPE and MRSA, SanoFog and SanoStatic were comparable in performance. For C. difficile we concluded the following: SanoFog was most effective for disinfection of C. difficile spores when compared to SanoStatic. CONCLUSION: Whereas SanoFog and SanoStatic were effective against bacterial cells, the current practice of using SanoFog and SanoStatic together would be effective for disinfection of C. difficile spores based on investigations under the conditions of experimentation reported here. The spore strips results were not comparable to the results either for the vegetation cells (VRE, ESBLK, CPE, and MRSA) or for C. difficile spores.

Regulation of E-cadherin-mediated adhesion by muscarinic acetylcholine receptors in small cell lung carcinoma.

We present the first evidence that adhesion mediated by a member of the cadherin gene family can be regulated by a G protein-coupled receptor. We show that activating the M3 muscarinic acetylcholine receptor (mAChR) rapidly induces E-cadherin-mediated adhesion in a small cell lung carcinoma (SCLC) cell line. This response is inhibited by E-cadherin antibodies, and does not occur in another SCLC cell line which expresses functional mAChR but reduced levels of E-cadherin. Protein kinase C may be involved, since phorbol 12-myristate 13-acetate also induces E-cadherin-mediated aggregation. Immunofluorescence analyses indicate that mAChR activation does not grossly alter E-cadherin surface expression or localization at areas of cell-cell contact, suggesting mAChR activation may increase E-cadherin binding activity. Our findings suggest that G protein-coupled receptors may regulate processes involving cadherin-mediated adhesion, such as embryonic development, neurogenesis, and cancer metastasis.

Continuous generation of volumetric images during stereotactic body radiation therapy using periodic kV imaging and an external respiratory surrogate.

We present a technique for continuous generation of volumetric images during SBRT using periodic kV imaging and an external respiratory surrogate signal to drive a patient-specific PCA motion model. Using the on-board imager, kV radiographs are acquired every 3 s and used to fit the parameters of a motion model so that it matches observed changes in internal patient anatomy. A multi-dimensional correlation model is established between the motion model parameters and the external surrogate position and velocity, enabling volumetric image reconstruction between kV imaging time points. Performance of the algorithm was evaluated using 10 realistic eXtended CArdiac-Torso (XCAT) digital phantoms including 3D anatomical respiratory deformation programmed with 3D tumor positions measured with orthogonal kV imaging of implanted fiducial gold markers. The clinically measured ground truth 3D tumor positions provided a dataset with realistic breathing irregularities, and the combination of periodic on-board kV imaging with recorded external respiratory surrogate signal was used for correlation modeling to account for any changes in internal-external correlation. The three-dimensional tumor positions are reconstructed with an average root mean square error (RMSE) of 1.47 mm, and an average 95th percentile 3D positional error of 2.80 mm compared with the clinically measured ground truth 3D tumor positions. This technique enables continuous 3D anatomical image generation based on periodic kV imaging of internal anatomy without the additional dose of continuous kV imaging. The 3D anatomical images produced using this method can be used for treatment verification and delivered dose computation in the presence of irregular respiratory motion.

Anomalous mechanical behavior of nanocrystalline binary alloys under extreme conditions.

Fundamentally, material flow stress increases exponentially at deformation rates exceeding, typically, ~103 s-1, resulting in brittle failure. The origin of such behavior derives from the dislocation motion causing non-Arrhenius deformation at higher strain rates due to drag forces from phonon interactions. Here, we discover that this assumption is prevented from manifesting when microstructural length is stabilized at an extremely fine size (nanoscale regime). This divergent strain-rate-insensitive behavior is attributed to a unique microstructure that alters the average dislocation velocity, and distance traveled, preventing/delaying dislocation interaction with phonons until higher strain rates than observed in known systems; thus enabling constant flow-stress response even at extreme conditions. Previously, these extreme loading conditions were unattainable in nanocrystalline materials due to thermal and mechanical instability of their microstructures; thus, these anomalies have never been observed in any other material. Finally, the unique stability leads to high-temperature strength maintained up to 80% of the melting point (~1356 K).

Low Altitude Solar Magnetic Reconnection, Type III Solar Radio Bursts, and X-ray Emissions.

Type III solar radio bursts are the Sun's most intense and frequent nonthermal radio emissions. They involve two critical problems in astrophysics, plasma physics, and space physics: how collective processes produce nonthermal radiation and how magnetic reconnection occurs and changes magnetic energy into kinetic energy. Here magnetic reconnection events are identified definitively in Solar Dynamics Observatory UV-EUV data, with strong upward and downward pairs of jets, current sheets, and cusp-like geometries on top of time-varying magnetic loops, and strong outflows along pairs of open magnetic field lines. Type III bursts imaged by the Murchison Widefield Array and detected by the Learmonth radiospectrograph and STEREO B spacecraft are demonstrated to be in very good temporal and spatial coincidence with specific reconnection events and with bursts of X-rays detected by the RHESSI spacecraft. The reconnection sites are low, near heights of 5-10 Mm. These images and event timings provide the long-desired direct evidence that semi-relativistic electrons energized in magnetic reconnection regions produce type III radio bursts. Not all the observed reconnection events produce X-ray events or coronal or interplanetary type III bursts; thus different special conditions exist for electrons leaving reconnection regions to produce observable radio, EUV, UV, and X-ray bursts.

The Nogo-B receptor promotes Ras plasma membrane localization and activation.

The localization of prenylated Ras at the plasma membrane promotes activation of Ras by receptor tyrosine kinases and stimulates oncogenic signaling by mutant Ras. The Nogo-B receptor (NgBR) is a transmembrane receptor that contains a conserved hydrophobic pocket. Here, we demonstrate that the NgBR promotes the membrane accumulation of Ras by directly binding prenylated Ras at the plasma membrane. We show that NgBR knockdown diminishes the membrane localization of Ras in multiple cell types. NgBR overexpression in NIH-3T3 fibroblasts increases membrane-associated Ras, induces the transformed phenotype in vitro, and promotes the formation of fibrosarcoma in nude mice. NgBR knockdown in human breast cancer cells reduces Ras membrane localization, inhibits epidermal growth factor (EGF)-stimulated Ras signaling and diminishes tumorigenesis of xenografts in nude mice. Our data demonstrate that NgBR is a unique receptor that promotes accumulation of prenylated Ras at the plasma membrane and promotes EGF pathways.

SmgGDS is a transient nucleolar protein that protects cells from nucleolar stress and promotes the cell cycle by regulating DREAM complex gene expression.

The chaperone protein and guanine nucleotide exchange factor SmgGDS (RAP1GDS1) is a key promoter of cancer cell proliferation and tumorigenesis. SmgGDS undergoes nucleocytoplasmic shuttling, suggesting that it has both cytoplasmic and nuclear functions that promote cancer. Previous studies indicate that SmgGDS binds cytoplasmic small GTPases and promotes their trafficking to the plasma membrane. In contrast, little is known about the functions of SmgGDS in the nucleus, or how these nuclear functions might benefit cancer cells. Here we show unique nuclear localization and regulation of gene transcription pathways by SmgGDS. Strikingly, SmgGDS depletion significantly reduces expression of over 600 gene products that are targets of the DREAM complex, which is a transcription factor complex that regulates expression of proteins controlling the cell cycle. The cell cycle regulators E2F1, MYC, MYBL2 (B-Myb) and FOXM1 are among the DREAM targets that are diminished by SmgGDS depletion. E2F1 is well known to promote G1 cell cycle progression, and the loss of E2F1 in SmgGDS-depleted cells provides an explanation for previous reports that SmgGDS depletion characteristically causes a G1 cell cycle arrest. We show that SmgGDS localizes in nucleoli, and that RNAi-mediated depletion of SmgGDS in cancer cells disrupts nucleolar morphology, signifying nucleolar stress. We show that nucleolar SmgGDS interacts with the RNA polymerase I transcription factor upstream binding factor (UBF). The RNAi-mediated depletion of UBF diminishes nucleolar localization of SmgGDS and promotes proteasome-mediated degradation of SmgGDS, indicating that nucleolar sequestration of SmgGDS by UBF stabilizes SmgGDS protein. The ability of SmgGDS to interact with UBF and localize in the nucleolus is diminished by expressing DiRas1 or DiRas2, which are small GTPases that bind SmgGDS and act as tumor suppressors. Taken together, our results support a novel nuclear role for SmgGDS in protecting malignant cells from nucleolar stress, thus promoting cell cycle progression and tumorigenesis.

Regulation of cadherin-mediated adhesion by the small GTP-binding protein Rho in small cell lung carcinoma cells.

Metastasis is one of the most important factors responsible for the pathogenesis of small cell lung carcinoma (SCLC). SCLC cells express cadherins, which are homophilic cell-cell adhesion molecules that play an important role in the regulation of metastasis. We present the first evidence that altering the activity of the small GTP-binding protein Rho induces cadherin-mediated adhesion. ADP-ribosylation of Rho upon incubation or electroporation with recombinant C3 exoenzyme induces rapid aggregation and compaction of SCLC cells. Aggregation and compaction induced by C3 exoenzyme are diminished by removal of extracellular Ca2+ and by the HECD blocking antibody to E-cadherin but not by antibodies to other adhesion molecules. Altering the activity of Rho by ADP-ribosylation does not alter surface expression of E-cadherin, but it alters G actin content, as indicated by the binding of DNase I. Treatment with cytochalasin D also alters G actin content and increases aggregation and compaction of SCLC cells. These findings implicate Rho in the regulation of cadherin-mediated adhesion and identify Rho as a potential therapeutic target for the control of SCLC metastasis.

Small cell lung carcinoma exhibits greater phospholipase C-beta1 expression and edelfosine resistance compared with non-small cell lung carcinoma.

Aberrant signal transduction pathways involved in the development of metastatic disease are poorly defined in both small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). Neuropeptide-driven positive feedback loops stimulating cell proliferation are characteristic of SCLC. The activation of phospholipase C (PLC)-beta1 is an early and common response to stimulation of G protein-coupled receptors by these neuroendocrine growth factors. The importance of PLC-beta in neuropeptide signaling prompted us to compare PLC-beta isoform expression and activity in four independent SCLC cell lines and four independent NSCLC cell lines. We found that PLC-beta1 is more highly expressed in SCLC than in NSCLC, as indicated by Western blotting of cell lysates. All SCLC lines studied express PLC-beta1; only one of the NSCLC lines investigated showed detectable levels of the enzyme. NSCLC lines are significantly more sensitive to the antiproliferative effects of ET-18-OCH3 (edelfosine) compared with the SCLC lines, as indicated by [3H]thymidine uptake. The only SCLC cell line (NCI-H345) that is as sensitive as the NSCLC cell lines to ET-18-OCH3 also expresses uniquely low levels of PLC-beta1. The participation of PLC-beta1 in signaling by SCLC growth factor receptors is indicated by our finding that PLC-beta1 (but not PLC-beta3) coimnunoprecipitates with G(alpha)q/11 upon activation of neurotensin receptors; this association is inhibited by ET-18-OCH3. Ca2+ mobilization mediated by neurotensin receptors is also inhibited by ET-18-OCH3. The binding of GTPgammaS to G(alpha)q/11 upon treatment of SCLC cells with neurotensin is not inhibited by ET-18-OCH3. These findings indicate that ET-18-OCH3 does not interfere with G(alpha)q/11 activation but rather inhibits the association of G(alpha)q/11 with PLC-beta1. Our data suggest that PLC-beta is an important mediator of both SCLC and NSCLC proliferation. Differences in PLC-beta1 expression may be exploitable in the development of effective diagnostic and therapeutic tools.

A hormone priming regimen and hibernation affect oviposition in the boreal toad (Anaxyrus boreas boreas).

Declines of the southern Rocky Mountain population of boreal toad (Anaxyrus boreas boreas) have led to the establishment of a captive assurance population and reintroduction program, in an attempt to preserve and propagate this geographically isolated population. One of the unique adaptations of this species is its ability to survive in cold environments by undergoing long periods of hibernation. In captivity, hibernation can be avoided altogether, decreasing morbidity caused by compromised immune systems. However, it is not entirely clear how essential hibernation is to reproductive success. In this study, the effects of hibernation versus nonhibernation, and exogenous hormones on oviposition, were examined in boreal toad females in the absence of males. In the summers of 2011 and 2012, 20 females housed at Mississippi State University were treated with a double priming dose of hCG and various ovulatory doses of hCG and LH-releasing hormone analog but denied hibernation. Exogenous hormones, in the absence of hibernation, could not induce oviposition over two breeding seasons (2011-2012). In contrast, during the summer of 2012 and 2013, 17 of 22 females (77%) housed at the Native Aquatic Species Restoration Facility (Alamosa, CO, USA) oviposited after they were treated with two priming doses of hCG (3.7 IU/g each) and a single ovulation dose of hCG (13.5 IU/g) and LH-releasing hormone analog (0.4 µg/g) after hibernation. There was a significant difference in oviposition between females that were hibernated and received hormones (2012, P < 0.05 and 2013, P < 0.01) compared to hibernated control females. In 2013, 12 of 16 remaining Mississippi State University females from the same group used in 2011 and 2012 were hibernated for 1, 3, and 6 months, respectively and then treated with the same hormone regimen administered to females at the Native Aquatic Species Restoration Facility. Together, hibernation and hormone treatments significantly increased oviposition (P < 0.05), with 33% of females ovipositing. These results suggest that (1) hibernation is a key factor influencing oviposition that cannot be exclusively circumvented by exogenous hormones; (2) females do not require the presence of a male to oviposit after hormone treatments; and (3) longer hibernation periods are not beneficial for oviposition. The hormonal induction of oviposition in the absence of males and shorter hibernation periods could have important captive management implications for the boreal toad. Furthermore, the production of viable offspring by IVF where natural mating is limited could become an important tool for genetic management of this boreal toad captive population.

Radiotelemetric monitoring of hypothalamic gonadotropin-releasing hormone pulse generator activity throughout the menstrual cycle of the rhesus monkey.

Continuous monitoring of the electrophysiological manifestations of GnRH pulse generator activity was achieved by radiotelemetry throughout the menstrual cycles of unrestrained rhesus monkeys. The characteristic increases in hypothalamic multiunit activity (MUA volleys) associated with each LH pulse measured in the peripheral circulation were of lower frequency during the luteal phase than in the follicular phase of the cycle. Multiunit activity volley frequency increased as functional luteolysis progressed and achieved maxima of approximately one volley per hour within the first few days of the follicular phase. Unexpectedly, a dramatic decline in pulse generator frequency was observed coincidentally with the initiation of the preovulatory LH surge. Evidence is presented to support the conclusion that this deceleration of pulse generator activity is the consequence of the preovulatory rise in plasma estrogen concentration. As reported in women, a significant reduction in GnRH pulse generator frequency was observed at night during the follicular phase, but not during the luteal phase, of the menstrual cycle.

Preventive cardiology in primary care.

Primary care physicians play a pivotal role in the successful implementation of the National Cholesterol Educational Program (NCEP) guidelines for both population and high-risk approaches to reduce blood cholesterol levels in children and adults. Increasingly, in this era of health cost containment, the primary care physician is recognized as (1) the main and sometimes the only source of health care for large numbers of individuals; (2) the affordable physician and (3) the gatekeeper for referral to medical specialists. Achievement of NCEP guidelines for cholesterol reduction, American Heart Association (AHA) guidelines for prevention of cardiovascular disease, and Year 2000 National Objectives for Health Promotion and Disease Prevention will all rely heavily on the active cooperation and support of practicing internists, pediatricians, and family/general practitioners in providing patient education, risk factor evaluation and intervention. Although the majority of primary care physicians intuitively support the concept of preventive cardiology and generally have a high level of knowledge of cardiovascular risk factors, a significant gap remains between physician knowledge and attitudes and the actual practice of preventive cardiology in clinical practice. Despite these limitations in implementation of clinical guidelines, significant progress has been made in the past decade in reaching NCEP and Year 2000 goals for population-wide cholesterol reduction.

Is a high-fiber diet safe for children?

OBJECTIVES: Although dietary fiber is associated with important health benefits in childhood, there have been concerns that very high fiber diets may result in adverse health effects. This report reviews the major safety concerns associated with consumption of very high fiber diets, estimates the amount of fiber that may cause adverse physiologic effects in children, and proposes safe levels of dietary fiber intake for children and adolescents. METHODS: Published studies on dietary fiber intake in childhood were reviewed to determine major safety concerns, to document adverse effects, to characterize subjects involved and the dose and type of fiber consumed, and to estimate potential relevance to US children and adolescents. Levels of dietary fiber reported to have adverse health effects were compared with recommended levels of fiber intake for children older than 2 years of age. RESULTS AND CONCLUSIONS: A review of the scientific literature suggests that a small loss of energy, protein, and fat may occur with a high intake of dietary fiber. However, this small loss of energy is unlikely to be significant to children consuming adequate levels of major nutrients, especially at conservative fiber intakes as recommended by the American Health Foundation's age plus 5 formula. In addition, it is estimated that even with a doubling of current dietary fiber, there is unlikely to be an adverse effect on serum vitamin and mineral concentrations in healthy US children consuming a balanced diet containing adequate levels of nutrients. Thus, evidence suggests that for US children, a moderate increase in dietary fiber is more likely to be healthful than harmful.