The association between antibiotic use in infancy and childhood overweight or obesity: a systematic review and meta-analysis.

PURPOSE: Antibiotic use is associated with alteration of the gut microbiome and metabolic activity. As childhood obesity is a predisposing factor for adult obesity, addressing childhood risk factors to weight gain in early life is important. This review aims to investigate the association between infant antibiotic exposure (aged < 24 months) and childhood obesity or overweight. METHODS: Articles were retrieved from CINAHL, Cochrane CENTRAL, Embase and MEDLINE. Eligible articles investigated antibiotic use in exposed versus unexposed infants and measured childhood weight change. Data were synthesized narratively and meta-analysed where possible. RESULTS: After title/abstract and full-text screening, 17 articles representing 15 unique studies were included for narrative synthesis. We found a small association between antibiotic exposure in infancy (<24 months) and childhood overweight or obesity. The strongest associations were observed in boys versus girls and children exposed to multiple antibiotic courses or broad-spectrum drugs. Meta-analysis of 12 sets of results comparing the earliest age of exposure to any antibiotic with overweight or obesity at the latest age of outcome found a pooled odds ratio of 1.05 (95% confidence interval: 1.00-1.11). CONCLUSIONS: Antibiotic exposure in infants, aged < 24 months, was associated with a small increase in odds of childhood overweight or obesity in some subgroups of children.

Synchronization in a noise-driven developing neural network.

We use computer simulations to investigate the structural and dynamical properties of a developing neural network whose activity is driven by noise. Structurally, the constructed neural networks in our simulations exhibit the small-world properties that have been observed in several neural networks. The dynamical change of neuronal membrane potential is described by the Hodgkin-Huxley model, and two types of learning rules, including spike-timing-dependent plasticity (STDP) and inverse STDP, are considered to restructure the synaptic strength between neurons. Clustered synchronized firing (SF) of the network is observed when the network connectivity (number of connections/maximal connections) is about 0.75, in which the firing rate of neurons is only half of the network frequency. At the connectivity of 0.86, all neurons fire synchronously at the network frequency. The network SF frequency increases logarithmically with the culturing time of a growing network and decreases exponentially with the delay time in signal transmission. These conclusions are consistent with experimental observations. The phase diagrams of SF in a developing network are investigated for both learning rules.

Familial incidence of Paget's disease and secondary osteogenic sarcoma. A report of three cases from a single family.

This report describes a family of three siblings with a long history of polyostotic Paget's disease. Because of the severe osseous involvement with Paget's disease, all three patients had problems that required orthopedic surgery. Subsequent to these surgeries, two patients developed osteogenic sarcoma at sites unrelated to their past procedures, one in the sacrum and one in the calvarium. Both patients died shortly after their diagnosis because of the aggressive spread of the tumor. Although the etiology of Paget's disease and its complication of osteogenic sarcoma still remain to be clarified, this and other case reports suggest a possible environmental or hereditary contribution to developing osteogenic sarcoma in Paget's disease. Patients with a familial clustering of polyostotic Paget's disease may benefit from more thorough screening tests to detect malignant transformation.

Paget's disease in the hand: correlation of magnetic resonance imaging with histology.

A 62-year-old white woman was seen initially with a 4-month history of swelling over the dorsum of her wrist and thumb pain at the basal joint. Radiographs revealed pantrapezial arthritis and a marked increase in the radiodensity of the capitate. Tomograms showed slight enlargement of the capitate, and magnetic resonance imaging revealed a dramatic decrease in the signal intensity on T1- and T2-weighted images. A biopsy of the capitate was done at the time of thumb carpometacarpal joint arthroplasty. Active Paget's disease was diagnosed. It is postulated that loss of marrow fat in active Paget's disease decreased the T1- and T2-weighted signals in a manner similar to processes, such as Gaucher's disease and osteonecrosis.

Estimation of cell survival by flow cytometric quantification of fluorescein diacetate/propidium iodide viable cell number.

We report a flow cytometric method to quantify the number of viable cells remaining in suspension culture following exposure to cytotoxic drugs. Cell viability is assessed by flow cytometric measurement of cellular fluorescence after staining with fluorescein diacetate and propidium iodide in isotonic solution. The number of viable cells per ml of culture is determined by a timed count of viable cells and from knowledge of the flow cytometer sample flow rate. P388 murine or HL-60 human leukemia cells in culture were used as model systems. This method can quantify accurately viable cell concentrations in suspension culture from 100 cells/ml to 1 million cells/ml. The sensitivity of the method as a cytotoxicity assay increases if, following brief (1-4-h) exposure to drug, greater time is allowed for cell death and lysis to occur prior to flow cytometric counting of viable cells. If the viability assessment is deferred for at least 72 h following drug (daunorubicin, actinomycin D, vincristine) exposure, results were obtained approximating those obtained from the soft agar clonogenic assay or the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. In studying the cytotoxic effects of vincristine, actinomycin D, 1-beta-D-arabinofuranosylcytosine, and daunorubicin on P388 or HL-60 cells sensitive and resistant to these agents, reasonable results were obtained by flow cytometric counting of viable cell number. We have been able to perform this flow cytometric viability assay with ease using bone marrow blast cells obtained from patients with acute myelogenous leukemia. The method is facile, relatively rapid, and since it is ideal for studying cells in suspension culture, its potential as a predictor of chemotherapeutic response in leukemia warrants further evaluation.

Bromodeoxyuridine enhancement of 1-beta-D-arabinofuranosylcytosine metabolic activation and toxicity in HL-60 leukemic cells.

We tested whether bromodeoxyuridine (BrdUrd), an analogue of thymidine (dThd), enhances 1-beta-D-arabinofuranosylcytosine (ara-C) metabolic activation, as does dThd. HL-60 cells were exposed to 10, 100, or 1000 nM ara-C for 3 h. Simultaneous exposure of log phase HL-60 cells to BrdUrd (1-1000 microM) and ara-C for 3 h resulted in enhancement of ara-C incorporation into DNA, with a doubling of incorporation in response to 10 nM ara-C occurring at concentrations of BrdUrd greater than 100 microM. Preexposure of cells to BrdUrd for 16 h followed by addition of ara-C for 3 h resulted in even greater ara-C incorporation into DNA. This increase was most marked at the lower concentrations of ara-C (10 and 100 nM), where approximately 3-fold enhancement of ara-C incorporation was observed in response to BrdUrd concentrations greater than 100 microM. Intracellular pools of 1-beta-D-arabinofuranosyl-CTP increased significantly (up to 3-fold) following 16-h exposure to BrdUrd (30, 100, or 300 microM) at all concentrations of ara-C tested. The ara-C phosphorylating activity of cell-free extracts obtained following 16-h exposure of cells to BrdUrd increased 1.5- to 2.3-fold over control. Intracellular dCTP pools fell to approximately 50% of control after exposure to 750 microM BrdUrd or dThd. Exposure to BrdUrd for 16 h caused a concentration-dependent increase in cells with S-phase DNA content, as assessed by flow cytometry, with a doubling of cells in S phase (to 60%) observed in response to 500 microM BrdUrd. HL-60 cells exposed to identical conditions of BrdUrd for 3 h showed no significant alteration in cell cycle phase distribution. Thus, although BrdUrd does increase cells in S phase, the increased ara-C incorporation caused by BrdUrd cannot be explained solely on a cytokinetic basis since enhancement of incorporation was observed after a 3-h exposure of cells to BrdUrd and ara-C. The combination of ara-C (100 nM) and BrdUrd (100-1000 microM) exhibited cytotoxic synergism, as measured by the fluorescein diacetate/propidium iodide method. These data demonstrate a clear potential for BrdUrd modulation of ara-C metabolism in human leukemia. Additionally, the interaction of BrdUrd and ara-C should be considered in the interpretation of studies of the effects of ara-C on DNA synthesis as measured by flow cytometric quantification of incorporated BrdUrd.

The buildup factor: effect of scatter on absolute volume determination.

We have developed a new method for generating attenuation-corrected images for use in absolute volume and activity measurements. The technique relies on the use of a set of measured buildup factors to correct for the effects of scatter inherent in the broad-beam conditions of clinical nuclear medicine and requires anterior and posterior count-rate measurements. The scatter correction requires that the well-known attenuation factor e-mud be replaced by 1-(1-e-mud)B(infinity), where B(infinity) is the buildup factor at infinite depth. The buildup factors for four different scintillation camera window settings and three different source sizes are reported. The method was validated by calculating phantom volumes and comparing the results to a previously reported technique which does not account for the scatter contribution by assuming mu = 0.15 cm-1. The results showed that the buildup factor method provides less than 7.3% error for volume determinations at all investigated depths, window settings, and source sizes, whereas errors of 3.3-26.7% were found with the other technique.

Tc-99m HIDA dosimetry in patients with various hepatic disorders.

The pharmacodynamics of Tc-99m dimethyliminodiacetic acid were studied for normal subjects and for patients with a variety of hepatobiliary disorders. It was determined that, in normal subjects, approximately 65% of the gallbladder agent bypassed the gallbladder and was excreted directly from the liver into the small intestine. This bypassing of the gallbladder was even higher in patients with cystic-duct or common-duct obstruction. The radiation burdens to the gallbladder wall and other critical organs were calculated using the dynamic data obtained from patients with a variety of gallbladder disease. The dose to the gallbladder wall was found to be significantly lower than previously reported. Gallbladder ejection and clearance characteristics when stimulated by food intake were studied for normal subjects. Dosimetry calculations demonstrated a fivefold reduction of absorbed dose to the gallbladder wall when the gallbladder was stimulated to contract using a fatty meal. Accordingly, a fatty meal is recommended for patients at the end of all gallbladder imaging studies.

Absolute left ventricular volume by an iterative build-up factor analysis of gated radionuclide images.

A method for determining absolute left ventricular (LV) volumes from radionuclide gated blood-pool (GBP) images was validated in 34 patients. The technique is nongeometric, corrects for tissue attenuation, and uses an experimentally determined set of build-up factors to account for the effects of scatter. Only four parameters are needed to determine LV volumes: the LV count rates from a left anterior oblique (LAO) and a right posterior oblique (RPO) image (180 degrees opposed to the LAO), a venous blood sample, and a patient thickness measurement. A computer algorithm is used to reach an iterative solution to two simultaneous equations that yield LV volumes. Phantom studies showed less than 4% error for volume determinations at all investigated depths. For the patients studied the correlation between volumes obtained by GBP and contrast ventriculography was 0.97 for diastole and 0.96 for systole.

Absolute quantitation of radioactivity using the buildup factor.

A quantitation scheme for absolute activity measurements with the gamma camera is presented. The technique relies on the use of a set of derived buildup factors to correct for the effects of scatter. Only anterior and posterior view count rates of the region of interest are required for quantitation. The buildup factors are reported for various depths for two different source sizes using the parallel-hole collimator with a specific window setting. Phantom studies have shown that the method provides less than 5% error for activity determinations at all investigated depths.

Ramapithecines from China: evidence from tooth dimensions.

Data obtained from ramapithecine specimens found in Asia, Africa and Europe have suggested the existence of two major subgroups, Ramapithecus and Sivapithecus, with Ramapithecus having pre-human status. Recently, however, it has been proposed that the fossils all belong to a single group, Sivapithecus, which is more closely related to the apes, in particular the orang-utan. Here we analyse data from a series of similar fossils which have been found in late Miocene coalfields in Lufeng, Yunnan Province, China. These include a number of almost complete jaws and five partial skulls which are more complete than any others so far known. A statistical analysis of the overall dimensions of the large number of teeth included in these finds shows that the differences between the groups previously assigned to Ramapithecus and Sivapithecus are greater than those found between the sexes in the most sexually dimorphic of the living great apes. Within the groups the distribution is bimodal and we suggest each group contains sex subgroups.

Radiation dose estimates for oral agents used in upper gastrointestinal disease.

Radiation dosimetry was calculated for a number of orally administered radiopharmaceuticals used for study of upper gastrointestinal function. These include: Tc-99m sulfur colloid in water, in a cooked egg, and in chicken liver labeled in vivo; In-111 DTPA; Tc-99m DTPA; In-113m DTPA; Tc-99m ovalbumin in cooked egg; and In-111 colloid in chicken liver labeled in vivo. Radiation burdens to the stomach, small intestine, upper and lower large intestine, ovaries, testes, and total body are calculated for each preparation.

20-kilobar pressure system.

A reciprocating hand pump capable of generating hydrostatic pressure to 20 kilobars has been constructed for high-pressure magnetic resonance studies. The pump body and the high-pressure cell are two separate units, which are connected by a high-pressure tubing using connectors modified from a design of an unsupported area seal due to Warschauer and Paul. This makes high-pressure magnetic resonance work possible by reducing the required work space between the gap of the magnet pole faces.

K-band high-pressure cell for ENDOR studies.

This article describes a versatile high-pressure K-band EPR-ENDOR system, designed for the examination of the effects of hydrostatic pressure on F-center hyperfine interactions. Dielectric filling is used to minimize the inner dimensions of the pressure cell. Cavity mode and coil geometry permit the same system to be used either for high-frequency field modulation EPR or for ENDOR by rotating the magnetic field. The pressure seal is also part of a rotatable microwave joint permitting the microwave coupling to be varied by rotating the cavity-pressure cell assembly. The beryllium-copper high-pressure vessel is separated from the pressure generating device by high-pressure transmitting tubing. It has been tested to 18 kilobars.

Improved technique for obtaining teletherapy portal radiographs with high-energy photons.

H & D curves were obtained for various film/screen combinations exposed to 60Co, 4-MV, and 45-MV photons. Data indicate that contrast is enhanced more by light-emitting screens than by lead screens or direct exposure. Flexible film cassettes are more comfortable for the patient, and extra-large film can be used for larger patients.