Antibiotic use and childhood body mass index trajectory.

BACKGROUND/OBJECTIVES: Antibiotics are commonly prescribed for children. Use of antibiotics early in life has been linked to weight gain but there are no large-scale, population-based, longitudinal studies of the full age range among mainly healthy children. SUBJECTS/METHODS: We used electronic health record data on 163 820 children aged 3-18 years and mixed effects linear regression to model associations of antibiotic orders with growth curve trajectories of annual body mass index (BMI) controlling for confounders. Models evaluated three kinds of antibiotic associations-reversible (time-varying indicator for an order in year before each BMI), persistent (time-varying cumulative orders up to BMIj) and progressive (cumulative orders up to prior BMI (BMIj-1))-and whether these varied by age. RESULTS: Among 142 824 children under care in the prior year, a reversible association was observed and this short-term BMI gain was modified by age (P<0.001); effect size peaked in mid-teen years. A persistent association was observed and this association was stronger with increasing age (P<0.001). The addition of the progressive association among children with at least three BMIs (n=79 752) revealed that higher cumulative orders were associated with progressive weight gain; this did not vary by age. Among children with an antibiotic order in the prior year and at least seven lifetime orders, antibiotics (all classes combined) were associated with an average weight gain of approximately 1.4 kg at age 15 years. When antibiotic classes were evaluated separately, the largest weight gain at 15 years was associated with macrolide use. CONCLUSIONS: We found evidence of reversible, persistent and progressive effects of antibiotic use on BMI trajectories, with different effects by age, among mainly healthy children. The results suggest that antibiotic use may influence weight gain throughout childhood and not just during the earliest years as has been the primary focus of most prior studies.

Epigenetic alterations and decreasing insecticide sensitivity of the Asian tiger mosquito Aedes albopictus.

A range of environmental factors, including chemicals, can affect epigenetic processes in organisms leading to variations in phenotype. Thus, epigenetics displays an important environmentally responsive element. The transgenerational impact of environmental stressors on DNA methylation and phenotype was the focus of this study. The influence of two known DNA methylation-changing agents, the phytoestrogen genistein and the fungicide vinclozolin, on the overall DNA methylation level in the Asian tiger mosquito Aedes albopictus was investigated. The experiment comprised four generations in a full life-cycle design with an exposed parental generation and three consecutive non-exposed offspring generations. Application of the methylation agents to the parental generation of the study led to an alteration of the global DNA methylation level of the exposed individuals and those in two subsequent generations. The phenotypic variability of the offspring generations was assessed by examining their insecticide sensitivity. Here, a significant decrease in sensitivity (p<0.01) towards the model insecticide imidacloprid revealed alterations of the mosquito's phenotype in two subsequent generations. Thus, the evaluation of A. albopictus from an epigenetic perspective can contribute important information to the study of the high adaptability of this invasive disease vector to new environments, and its underlying mechanisms.

[Small renal mass]. / Der kleine Nierentumor.

The frequent application of ultrasound and radiological imaging for non-urological indications in recent years has resulted in an increase in the diagnosis of small renal masses. The treatment options for patients with a small renal mass include active surveillance, surgery (both open and minimally invasive) as well as ablative techniques. As there is a risk for metastatic spread even in small renal masses surgical extirpation remains the treatment of choice in most patients. Ablative procedures, such as cryoablation and radiofrequency ablation are appropriate for old and multi-morbid patients who require active treatment of a small renal mass. Active surveillance is an alternative for high-risk patients. Meticulous patient selection by the urologist and patient preference will determine the choice of treatment option in the future.

ERES (ER exit sites) and the "secretory unit concept".

The higher plant Golgi apparatus consists of hundreds of individual Golgi stacks which move along the cortical ER, propelled by the actomysin system. Anterograde and retrograde transport between the endoplasmic reticulum (ER) and the plant Golgi occurs over a narrow interface (around 500 nm) and is generally considered to be mediated by COP-coated vesicles. Previously, ER exit sites (ERES) have been identified on the basis of to localization of transiently expressed COPII-coat proteins. As a consequence it has been held that ERES in higher plants are intimately associated with Golgi stacks, and that both move together as an integrated structure: the "secretory unit". Using a new COPII marker, as well as YFP-SEC24 (a bona fide COPII coat protein), we have made observations on tobacco leaf epidermis at high resolution in the CLSM. Our data clearly shows that COPII fluorescence is associated with the Golgi stacks rather than the surface of the ER and probably represents the temporary accumulation of COPII vesicles in the Golgi matrix prior to fusion with the cis-Golgi cisternae. We have calculated the numbers of COPII vesicles which would be required to provide a typical Golgi-associated COPII-fluorescent signal as being much less than 20. We have discussed the consequences of this and question the continued usage of the term "secretory unit".

[Periprosthetic femoral bone reaction after total hip arthroplasty with preservation of the collum femoris : CT-assisted osteodensitometry 1 and 3 years postoperatively]. / Periprothetische femorale Knochenreaktion nach schenkelhalserhaltender Hüftendoprothetik : CT-gestützte Osteodensitometrie 1 und 3 Jahre postoperativ.

BACKGROUND: Short-stemmed cementless femoral components in total hip arthroplasty have been designed to preserve the proximal femoral bone stock by load transfer to the femoral metaphysis. An in vivo method of computed tomography-assisted (CT) osteodensitometry after total hip arthroplasty is presented which differentiates between cortical and cancellous bone density (BD) changes around uncemented femoral components. PATIENTS AND METHODS: Cortical and cancellous periprosthetic femoral BD (mg Ca HA/ml) was determined prospectively in 31 patients at day 10, 1 year and 3 years after total hip arthroplasty with preservation of the collum femoris (C.F.P.-stem, Link, Hamburg, Germany) using computed tomography-assisted osteodensitometry. Clinical results (Harris hip score) and plain x-rays were assessed in all cases. RESULTS: Progressive proximal cortical BD loss was observed between the 1 year (Ø -8%) and 3 year (Ø -22%) postoperative measurements. Distal to the trochanter minor no significant cortical BD changes were observed. Proximal cancellous BD decreased progressively between the 1 year (Ø -33%) and 3 year (Ø -45%) analyses. The Harris hip score improved from 45 points pre-operatively to 93 points at the 3 year follow-up. All x-rays showed signs of stable ingrowth. CONCLUSION: Periprosthetic CT osteodensitometry has the technical ability to discriminate between cortical and cancellous bone structures with respect to strain-adapted remodeling. Progressive proximal cortical and cancellous BD loss indicates that metaphyseal fixation cannot be achieved with the analyzed C.F.P. stem design. The lack of cortical BD loss below the trochanter minor suggests diaphyseal fixation of the implanted stem.

Control of vertically coupled InGaAs/GaAs quantum dots with electric fields.

Controllable interactions that couple quantum dots are a key requirement in the search for scalable solid state implementations for quantum information technology. From optical studies of excitons and corresponding calculations, we demonstrate that an electric field on vertically coupled pairs of In(0.6)Ga(0.4)As/GaAs quantum dots controls the mixing of the exciton states on the two dots and also provides controllable coupling between carriers in the dots.

Direct observation of controlled coupling in an individual quantum dot molecule.

We report the direct observation of quantum coupling in individual quantum dot molecules and its manipulation using static electric fields. A pronounced anticrossing of different excitonic transitions is observed as the electric field is tuned. A comparison of our experimental results with theory shows that the observed anticrossing occurs between excitons with predominant spatially direct and indirect character and reveals a field driven transition of the nature of the molecular ground state exciton wave function. Finally, the interdot quantum coupling strength is deduced optically and its dependence on the interdot separation is calculated.

Modeling the spread of annual influenza epidemics in the U.S.: the potential role of air travel.

The role of air travel in the global spread of influenza has been the subject of a significant body of research, but this question has yet to be explored within the U.S. The goal of this research is to explore whether knowledge of U.S. air travel patterns and volumes leads to better forecasting of epidemics. We report the results of a series of simulations for the 1998-1999 through 2000-2001 influenza seasons using a standard compartmental model coupled with air transportation data. These preliminary results suggest that air travel may play an important role in the spread of annual influenza within the U.S., particularly in cities with large air travel volumes.

A computed tomography assessment of femoral and acetabular bone changes after total hip arthroplasty.

Using computed tomography-assisted (CT) osteodensitometry, we studied the bone changes that occurred in 12 patients at 2 weeks and again at 1 year after total hip arthroplasty with insertion of a press-fit acetabular cup and an uncemented femoral tapered stem. There was a greater decrease in full bone density (BD) lateral to the femoral stem when compared to the medial side, at the proximal end of the femur this difference was significant (-22.1% versus -16.2%) ( P<0.001). At the tip of the stem cortical BD had decreased between 2.3% and 1.9% only. Proximal to the cup, the cortical BD increased by about 3.4% ( P< or =0.05), while the full BD decreased markedly by 8% ( P< or =0.001). These changes represent a response to a decrease in regional bone stress induced by the presence of the press-fit implant, and this might be considered as retro-acetabular stress shielding. No focal bone resorption was found.

Oogenesis in the marsupial stripe-faced dunnart, Sminthopsis macroura.

The timetable of oogenesis in Sminthopsis macroura is accelerated like in other marsupials showing relatively early maturation of the female. On the day of parturition (day 0) migration of primordial germ cells to the indifferent gonads has been completed. Follicular growth seems not to correspond to the biphasic pattern, in which oocyte and follicle grow synchronously until antral stages when only the follicle increases in size, but shows a continuous growth of the oocyte and the follicle up to the time of ovulation. During primordial and early primary follicle stage a paranuclear complex is present in the oocyte, consisting mainly of smooth tubules of endoplasmic reticulum. Cortical granules appear early in oocytes in secondary follicles. The conspicuous inclusions in the antral follicle are the clusters of electron-lucent vesicles in the oocyte. These inclusions grow from multivesicular bodies (MVB), which are formed from Golgi and endoplasmic reticulum vesicles. Further increase in the size of MVB involves the incorporation of endocytic vesicles and the coalescence of larger vesicles. The polarized nature of the oocyte at ovulation is due in part to the to accumulation of these vesicles in the cytoplasm opposite the eccentrically placed nuclear material.

Evaluation of a rapid optical immunoassay for influenza viruses (FLU OIA test) in comparison with cell culture and reverse transcription-PCR.

The FLU OIA test was evaluated with 146 throat swab specimens from subjects with a flu-like illness in six Canadian clinics during the 1999-2000 flu season. The rate of positivity of the FLU OIA test (41.5%) was significantly lower than that of cell culture (55.2%) or reverse transcription-PCR (55.9%) during a season in which only influenza A virus was detected.

Modulation of C5a-mediated effector functions of human polymorphonuclear leukocytes by tumor necrosis factor alpha and granulocyte macrophage colony-stimulating factor.

At the site of acute inflammation, leukocytes are confronted with multiple mediators which are expected to modulate each other with respect to cell responses to the individual ligand. In the present study, we compared the effects of the classical chemoattractants FMLP, PAF and LTB4, of the chemokine IL-8 and of TNFalpha, GM-CSF, IFN-gamma and IL-1beta on C5a-induced chemotaxis, degranulation, oxidative burst and expression of adhesion molecules of human neutrophils in vitro. Upon preincubation, TNFalpha as well as GM-CSF dose-dependently inhibited C5a-mediated chemotaxis, but augmented the release of elastase as well as respiratory burst activity. The effects of the two cytokines were accompanied by a downregulation of C5a receptors as determined by Scatchard analysis using (125)I-labeled C5a. Compared on a molar basis, TNFalpha was more effective than GM-CSF. C5a-induced expression of beta(2)-integrins was only moderately influenced by TNFalpha and GM-CSF. C5a itself diminished chemotaxis as well as degranulation and oxidative burst in response to a second dose of the same ligand (homologous desensitization), whereas heterologous desensitization by FMLP and IL-8 was restricted to C5a-induced degranulation or not observed (PAF, LTB4]. The cytokine effects are likely to be a consequence of altered C5a receptor expression as well as of postreceptor events. In concert with C5a, certain cytokines may shift neutrophil effector functions from migration to exocytosis, an essential step within the sequence of events in a coordinated inflammatory response.

Decreased physical function in juvenile rheumatoid arthritis.

OBJECTIVE: To assess the extent of physical disability in juvenile rheumatoid arthritis (JRA), classified according to subtype, and whether synovitis or flexion contractures are present on examination. METHODS: This retrospective study included 88 JRA patients and 50 controls without musculoskeletal disease. The outcome measure was the disability index (DI) derived from the Childhood Health Assessment Questionnaire (CHAQ). RESULTS: DI scores for JRA patients with synovitis (mean 0.49, range 0-1.88) and without synovitis (mean 0.37, range 0-1.75) were significantly higher (P < 0.001 for both groups) than for controls (mean 0.06, range 0-0.75, P < 0.001), but not significantly different from one another. Similarly, DI scores for JRA patients with and without any flexion contractures were higher than for controls, but not significantly different from one another. DI scores for JRA patients with both synovitis and flexion contractures were significantly higher than DI scores for JRA patients with neither, but were not distinguishable from JRA patients with synovitis only or flexion contractures only. Likewise, DI scores for JRA patients lacking synovitis and flexion contractures were not significantly different than those for JRA patients with one or the other. DI scores for systemic and polyarticular patients were higher than for pauciarticular patients, and DI scores for all 3 subtypes were higher than for controls. CONCLUSION: Our findings suggest that many JRA patients, including those with pauciarticular JRA, have problems with physical function, even when synovitis and flexion contractures are not present. Further attention and research is needed to elucidate the causes or origins of disability in JRA patients with seemingly well-controlled disease. We recommend that health status instruments like the CHAQ be more widely used for JRA patients to complement other assessments, especially in planning occupational and physical therapy.

Neutrophil priming by cytokines and vitamin D binding protein (Gc-globulin): impact on C5a-mediated chemotaxis, degranulation and respiratory burst.

At the site of acute inflammation, leukocytes are confronted with multiple mediators which are expected to modulate each other with respect to cell responses to the individual ligand. Previous contact of neutrophils with pro-inflammatory cytokines, such as TNF-alpha or GM-CSF, or with the vitamin D binding protein (Gc-globulin) leads to the alteration of either multiple or rather distinct C5a-mediated neutrophil functions. Gc-globulin, the transport protein for 25-(OH)-D3, serves selectively as a cochemotactic factor for C5a/Ca(des)Arg. In contrast, TNF-alpha and GM-CSF, previously shown to modulate FMLP-induced neutrophil responses, are able to reduce C5a-mediated neutrophil chemotaxis, but augment their degranulation and respiratory burst activity. Cytokine priming was shown to be accompanied by a down-regulation of C5a receptors (CD88) whereas vitamin D binding protein had no impact on the level of neutrophil C5a receptors. C5a itself diminishes chemotaxis as well as degranulation and oxidative burst in response to a second dose of the same ligand (homologous desensitization). A similar effect, termed heterologous desensitization, occurs, if cell responses to a given mediator (e.g. to C5a) are reduced or even abolished upon the activation of another receptor of the same G-protein coupled chemoattractant receptor subfamily (e.g. receptors for FMLP or IL-8). In concert with C5a, certain molecules may either augment chemotaxis or shift neutrophil effector functions from migration to exocytosis, an essential step within the sequence of events in a coordinated inflammatory response.

A comparison of oocyte organelles in Monodelphis domestica with those of other marsupials and eutherians.

This paper reviews the current knowledge of oocyte cytology in marsupials, particularly Monodelphis domestica, and eutherian mammals. Some of the conspicuous features will be described and their function discussed. Despite many fundamental similarities between the oocytes of eutherian mammals and marsupials, some aspects are different (e.g. growth pattern, final size, timetable of cytoplasmic maturation and utilization of storage material during early cleavage stages), when most of the vesicles are extruded into the perivitelline space in marsupials.

Cytokeratin expression in the developing vagina of the postnatal gerbil (Meriones unguiculatus).

During postnatal development the vaginal epithelium of the Mongolian gerbil is transformed from two to three layers into a stratified, first mucified subsequently keratinized squamous epithelium. Changes in the expression of cytokeratins were studied and the immunohistochemical results compared with the ultrastructural findings at the corresponding stage. The first 10 postnatal days (days pn) were characterized by a moderate, positive immunoreaction for pancytokeratin in all vaginal cell layers. A faint reaction was caused by mAB CK 18.01 against CK 1, 5, 6 and 8. The appearance of mucous granules in the luminal cells after 15 pn seemed to coincide with an increase in cytokeratins. The immunoresponse for pancytokeratin in these cells was very intense compared with the reaction in the basal cell layers. Mucocytes during development and at proestrus were the only cells which reacted faintly positive with mAB against CK 18 alone. The keratinizing epithelium, which differentiates after day 40 pn, reacted strongly positive for pancytokeratin in the keratinizing layers, desquamating, fully keratinized cells, however, showed a negative reaction. The data indicate that mucocytes are not transformed squamous keratinized cells, but represent a cell category with its individual differentiation potential. Vimentin was not expressed. Neither the epithelium of the sinus vagina nor of the Müllerian vagina displayed any response.

Isolation of granulosa-like cells from the bovine secretory corpus luteum and their characterization in long-term culture.

BACKGROUND: The isolation of cells termed type 5 from the bovine corpus luteum was recently reported. Since these cells were reminiscent of immature granulosa cells, their morphological and functional relationship requires further investigation in view of the novel concept of corpus luteum growth. It suggests that putative stem cells of unknown origin supply the pool of small luteal cells. METHODS: Bovine corpora lutea were mechanically dispersed, cell suspensions separated over a Percoll density gradient, and type 5 cells purified by colony transfer. Granulosa cells were harvested from small-sized antral follicles. Observations were carried out at the light and electron microscopical level. 3 beta-Hydroxy-steroid-dehydrogenase was localized histochemically in addition to intracellular lipid droplets stained with nile red. Immunolocalization was used to study Factor VIII antigen presence, the architecture of the cytoskeleton, as well as the occurrence of neuronal cell adhesion molecules, and of neuronal cadherin-like molecules. The uptake of acetylated low density lipoprotein was examined. As for progesterone concentration, cells were seeded at low density on day zero. Cell numbers and progesterone levels of supernatants were determined on day 10 in culture. RESULTS AND CONCLUSIONS: Type 5 cells behaved morphologically like immature granulosa cells, yet the total cell number and the progesterone concentration differed for type 5 cells compared to granulosa cells. The addition of LH had no influence on the progesterone concentration as seen for either type 5 cells or for granulosa cells. It is concluded that type 5 cells, which were originally mistaken for microvascular endothelial cells, display similarities with immature granulosa cells. Type 5 cells may play a role in renewal of luteal cells.

Postnatal development of the vaginal epithelium in the Mongolian gerbil (Meriones unguiculatus).

This study examines the normal postnatal (p.n.) development of the Mongolian gerbil's vagina from birth to the age when consistent cyclic changes of the estrus occur. At birth, the Müllerian vagina has a lumen and is lined by a pseudostratified or 2- to 3-layered epithelium. The cells contain large amounts of glycogen. The sinus vagina forms a solid plate and contains hardly any glycogen. During the first few p.n. days the cell layers separate, and the newly formed lumen becomes continuous with the Müllerian vagina. Only a vaginal closure membrane persists. Between p.n. days 10 and 15 the epithelium increases in height reaching 2-5 cell layers. The amount of glycogen diminishes, but in the luminal cells the first mucous granules develop. Leukocyte diapedesis starts, and immature Langerhans cells become discernible. Between p.n. days 18 and 30 the apical cells become mucified, and some shedding of these cells begins. Between p.n. days 36 and 45 bundles of keratin filaments appear in many of the luminal mucous cells intermingled with the mucous granules. In the middle layers keratin filaments, keratohyalin granules and membrane-coating granules indicate the beginning of the keratinization process. Diapedesis of leukocytes may lead to cell aggregations below top layers. By day 50 the shedding of the mucous cell layers reveals the underlying keratinized cell layers which then become exfoliated. The first steps of the estrous cycle show a heterogeneous pattern. At about p.n. day 60 the cycle becomes established.

Ultrastructural aspects of oocyte growth in the marsupial Monodelphis domestica (grey short-tailed opossum).

The growth of the opossum Monodelphis oocyte does not correspond to the strict biphasic pattern so far described in eutherians and marsupials. The oocyte increases appreciably in size during the last stage of antral follicle development. During the primordial and primary follicle stage Balbiani bodies or paranuclear complexes are not detectable in Monodelphis oocytes. Organelles are randomly distributed. In addition to the nucleolus, perichromatin and ribonucleoprotein particles are other intranuclear structures which occur as regular components in the early Monodelphis oocyte. Clusters of particles are mostly seen in close association with the nuclear envelope. Similar material has been encountered in the cytoplasm as a type of freely-existing 'nuage' material but never as mitochondria-associated 'nuage' or 'cement'. Both types of particles, intranuclear and cytoplasmic, disappear by the time antral follicle formation begins. Mitochondria are at first of the typical transformed shape seen in most mammalian oocytes. They are large, round or oval in outline with a few, often arched, cristae and a light matrix. During the primary follicle stage, mitochondrial size and complexity decrease and the matrix becomes electron dense. A close relationship between mitochondria and endoplasmic reticulum appears early in the primordial and later in the primary follicle oocyte. Regularly detected structures in the ooplasm of preantrum oocytes are paired or 'confronting' cisternae of endoplasmic reticulum, which are lamellar complexes comprised of 2 or more parallel cisternae with intervening electron-dense material. The most conspicuous inclusions in the Monodelphis oocytes of the tertiary and graafian follicles are vesicles. All other organelles are confined to the peripheral zone of the oocyte. Golgi and endoplasmic vesicles both take part in the formation of multivesicular bodies which seems to be the starting point for the vesicle accumulation. Further increase in size involves the incorporation of endocytotic vesicles and the coalescence of larger vesicles. Ordinary fixation procedure leave the vesicles empty. Cortical granules are found only in small numbers.

Postnatal development of the cervical epithelium in the Mongolian gerbil.

This study analyzes the postnatal development of the Mongolian gerbil's cervical epithelium, in relation to its future functions. In the newborn gerbil the outline of the cervical canal is smooth, showing hardly any signs of folding. The epithelium consists of 1 to 3 layers. The cervical cells have rounded apices of regular outline and contain a large amount of glycogen. The first secretory products of specific mucus type appear about day 23 postnatally (p.n.). Initially two types of vesicles can be identified, as compared with only one type in sexually mature animals. The process of mucification begins in the vagina and the external os of the cervix and spreads towards the cervical horns. The cervical canal, besides growing longer, becomes increasingly folded during development. At about day 50 p.n., with the onset of sexual maturity, an upper endocervix and a lower ectocervix can be distinguished within the cervical canal. In the fully mature animal, the endocervix consists of 4 to 5 layers, in which apical cells mucify and exfoliate. In the ectocervix, the epithelium can be divided into 4 to 5 basal layers and 5 to 7 upper layers which mucify, keratinize, and exfoliate, according to the cyclic phases of the vagina. Diapedesis of leucocytes through the epithelium starts around day 45 p.n.