Hedonic perception of odors in children aged 5-8 years is similar across 18 countries: Preliminary data.

OBJECTIVE: Olfactory preference emerges very early in life, and the sense of smell in children rapidly develops until the second decade of life. It is still unclear whether hedonic perception of odors is shared in children inhabiting different regions of the globe. METHODS: Five-hundred ten healthy children (N = 510; ngirls = 256; nboys = 254) aged from 5 to 8 years from 18 countries rated the pleasantness of 17 odors. RESULTS: The hedonic perception of odors in children aged between 5 and 8 years was rather consistent across 18 countries and mainly driven by the qualities of an odor and the overall ability of children to label odorants. CONCLUSION: Conclusions from this study, being a secondary analysis, are limited to the presented set of odors that were initially selected for the development of U-Sniff test and present null findings for the cross-cultural variability in hedonic perception of odors across 18 countries. These two major issues should be addressed in the future to either contradict or replicate the results presented herewith. This research lays fundament for posing further research questions about the developmental aspects of hedonic perception of odors and opens a new door for investigating cross-cultural differences in chemosensory perception of children.

A treat and extend regimen using ranibizumab for neovascular age-related macular degeneration clinical and economic impact.

PURPOSE: To evaluate the visual outcome, number of injections, and direct medical cost of a "treat and extend" regimen (TER) in managing neovascular age-related macular degeneration (nAMD) with intravitreal ranibizumab. DESIGN: Retrospective, interventional, consecutive case series. PARTICIPANTS: Ninety-two eyes of 92 patients met the entry criteria from May 2006 to May 2008. METHODS: All patients with treatment-naïve nAMD were treated monthly until no intraretinal or subretinal fluid was observed on optical coherence tomography (OCT). The treatment intervals were then sequentially lengthened by 2 weeks until signs of exudation recurred. The interval was individualized for each patient in an attempt to maintain an exudation-free macula. MAIN OUTCOME MEASURES: Change from baseline visual acuity, proportion of eyes losing < 3 lines and gaining ≥ 3 lines at 1 year of follow-up, annual mean number of injections, change from baseline OCT central retinal thickness (CRT), maximum period of extension, and adverse ocular and systemic events. RESULTS: The mean follow-up was 1.52 years. Mean Snellen visual acuity improved from 20/135 at baseline to 20/77 at 1 year follow-up (P < 0.001) and 20/83 at 2 years follow-up (P = 0.002). The proportion of eyes that lost < 3 Snellen visual acuity lines at final follow-up was 96% and the proportion that gained ≥ 3 Snellen visual acuity lines was 32%. The mean OCT CRT decreased from 303 µm at baseline to 238 µm at 1 year follow-up (P < 0.001). The mean number of injections over the first year and between years 1 and 2 was 8.36 and 7.45, respectively. The mean maximum period of extension was 79.9 days. No adverse ocular or systemic events were reported during the follow-up period. The direct annual medical cost per patient was $16,114.52 for the TER. The direct annual medical cost per patient ranged from $15,880.07 to $28,314.16 based on previous clinical trial protocols. CONCLUSIONS: Eyes with nAMD experienced significant visual improvement when managed with intravitreal ranibizumab using a TER. This treatment approach also was associated with significantly fewer patient visits, injections, and direct annual medical cost compared with monthly injections such as in the phase III clinical trials. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Association of multiple inflammatory markers with carotid intimal medial thickness and stenosis (from the Framingham Heart Study).

Inflammatory markers, particularly C-reactive protein (CRP), predict incident cardiovascular disease and are associated with the presence of subclinical atherosclerosis. The relations between multiple inflammatory markers and direct measures of atherosclerosis are less well established. Participants in the Offspring Cohort of the Framingham Heart Study (n = 2,885, 53% women, mean age 59 years) received routine assessments of common carotid artery intima-media thickness (CCA-IMT), internal carotid artery intima-media thickness (ICA-IMT), and the presence or absence of > or =25% carotid stenosis by ultrasonography. Circulating inflammatory markers assessed from an examination 4 years later included CRP, interleukin-6 (IL-6), intercellular adhesion molecule-1, monocyte chemoattractant protein-1, P-selectin, and CD40 ligand. Assessed as a group, inflammatory markers were significantly associated with ICA-IMT (p = 0.01), marginally with carotid stenosis (p = 0.08), but not with CCA-IMT. Individually, with an increase from the 25th to 75th percentile in IL-6, there were significant increases in ICA-IMT and carotid stenosis (for ICA-IMT, estimated fold increase 1.04, 95% confidence interval 1.03 to 1.06, p = 0.0004; for carotid stenosis, odds ratio 1.25, 95% confidence interval 1.06 to 1.47, p = 0.007) after adjustment for age, gender, and established risk factors for atherosclerosis. There was a similar significant multivariate-adjusted association of CRP with ICA-IMT but not with carotid stenosis. Smoking appeared to modify the associations of ICA-IMT with CRP (p = 0.009) and with IL-6 (p = 0.006); the association was more pronounced in current (vs former or never) smokers. In conclusion, there were modest associations of inflammatory markers, particularly IL-6, with carotid atherosclerosis. This association appears more pronounced in current smokers than in former smokers and nonsmokers.

Sensory profile in infants and toddlers with behavioral insomnia and/or feeding disorders.

BACKGROUND: Sleep and feeding difficulties are two common disorders in early childhood. It has been shown that feeding difficulties are more common among children with sleep disorders and vice versa. Since a child's characteristics play a substantial role in these two conditions, we aimed to investigate the sensory profile of infants and toddlers with behavioral insomnia (BI) or feeding disorders (FDs) in comparison with healthy age-matched controls. METHODS: Children aged 7-36 months with BI or FD were recruited from the sleep and feeding disorders clinics. Healthy controls were recruited from well-baby clinics. Parents completed a questionnaire which included demographics and socioeconomic status, as well as a sensory profile evaluation using the Infant/Toddler Sensory Profile (ITSP). RESULTS: Twenty-five children with BI, 28 with FDs and 32 controls were recruited. Oral processing scores were significantly lower in both BI and FD groups vs the controls (p = 0.015 and 0.001, respectively). Auditory processing scores were lower in the FD group vs the controls (p = 0.028). The scores of three out of the four ITSP sensory quadrants (Low Registration, Sensory Sensitivity, and Sensation Avoiding) were significantly lower in the FD group vs the controls (p = 0.027, 0.025, and 0.001, respectively), and in one quadrant (Sensation Avoiding) in the BI group vs the controls (p = 0.037). CONCLUSIONS: There were considerable differences in sensory processing, as reported by parents between children with BI and those with FDs compared to healthy controls, most often in the direction of the 'hypersensitive' profile. These differences may underlie the development and partially explain the coexistence of the two disorders. Sensory profile may be a target of intervention as part of the management of sleep and feeding disorders in early childhood.

Fractal analysis of region-based vascular change in the normal and non-proliferative diabetic retina.

PURPOSE: Evaluation of normal and abnormal vascular pattern in the human retina using a novel method: quantitative region-based fractal analysis. METHODS: Binary (black/white) vascular patterns of the human retina originating at the optic disc were obtained by semi-automatic computer processing of digital images from 60-degree fundus fluorescein angiography of 5 normal eyes and 5 eyes with non-proliferative diabetic retinopathy (NPDR). As determined by image resolution, vascular patterns included vessels with diameters >or=50 microm and excluded small vessels and capillaries. The density of linearized (i.e., skeletonized) vascular patterns in the macular region versus paramacular region (termed "region-based" linearized vascular pattern) was quantified with the fractal dimension (D(f)) and confirmed by grid intersection (rho(v)). RESULTS: By region-based quantification, D(f) and rho( v) were significantly higher in the normal macular region than in the NPDR macular region (p = 0.008 and p = 0.019, respectively). However, differences in D(f) and rho(v) between the normal and NPDR paramacular regions were not strongly significant (p = 0.168 and p = 0.337, respectively). CONCLUSIONS: Results from the retrospective analytical study demonstrate the feasibility of using quantitative region-based fractal analysis of early-stage vascular disease in the human retina. The results are encouraging for a broader study of diverse patient populations.

Bevacizumab for neovascular age-related macular degeneration using a treat-and-extend regimen: clinical and economic impact.

PURPOSE: To evaluate the visual outcomes, number of injections, and direct medical cost of a treat-and-extend regimen in managing neovascular age-related macular degeneration with intravitreal bevacizumab. DESIGN: Retrospective, interventional, consecutive case series. METHODS: Seventy-four eyes of 73 patients with treatment-naïve neovascular age-related macular degeneration from a single clinical practice were treated monthly with intravitreal bevacizumab until no intraretinal or subretinal fluid was observed on optical coherence tomography. The treatment intervals then were lengthened sequentially by 2 weeks until signs of exudation recurred and then were reduced accordingly to maintain an exudation-free macula. Main outcomes measured included mean change from baseline visual acuity, proportion of eyes losing fewer than 3 and gaining 3 or more Snellen visual acuity lines at 1 year of follow-up, annual mean number of injections, optical coherence tomography mean central retinal thickness change from baseline, mean maximum period of extension, adverse events, and mean direct annual medical cost. RESULTS: The mean follow-up period was 1.41 years. Mean Snellen visual acuity improved from 20/230 at baseline to 20/109 at 12 months (P < .001) and 20/106 at 24 months (P < .001). The mean number of injections over the first year was 7.94. The mean optical coherence tomography central retinal thickness decreased from 316 to 239 µm at 12 months (P < .001). The mean direct medical cost over the first year was $3493.85. CONCLUSIONS: Eyes with neovascular age-related macular degeneration experienced significant visual improvements on average when managed with intravitreal bevacizumab using a treat-and-extend regimen with fewer patient visits and injections along with lower costs compared with a fixed, monthly dosing regimen.

New mini-ColE1 as a molecular cloning vehicle.

A new mini-ColE1 plasmid, designated pAC105, was isolated. It has a molecular weight of 1.6 X 10(6) and carries information for its self-replication as well as information for conferring colicin E1 immunity upon its host. Furthermore, pAC105 undergoes replication in the presence of chloramphenicol even when a foreign deoxyribonucleic acid (pSC101) is inserted into its single EcoRI restriction site. Studies in minicell-producing strains demonstrate that pAC105 codes for only two or three polypeptides of low molecular weight. The advantages of using it as a molecular cloning vehicle are discussed.

Outer membrane protein a and other polypeptides regulate capsular polysaccharide synthesis in E. coli K-12.

capR (lon) mutants of Escherichia coli K-12 are mucoid on minimal agar because they produce large quantities of capsular polysaccharide. When such mutants are transformed to tetracycline resistance by plasmid pMC44, a hybrid plasmid that contains a 2 megadalton (Mdal) endonuclease EcoR1 fragment of E. coli K-12 DNA joined to the cloning vehicle-pSC101, capsular polysaccharide synthesis is inhibited and the transformed colonies exhibit a non-mucoid phenotype. Re-cloning of the 2 Mdal EcoR1 fragment onto plasmid pHA105, a min-colE1 plasmid, yielded plasmid pFM100 which also inhibited capsular polysaccharide synthesis in the capR mutants. A comparison of the polypeptides specified by both plasmids pFM100 and pMC44 in minicells demonstrated that seven polypeptide bands were specified by the 2 MDal DNA, one of which was previously demonstrated to be outer membrane protein a; also known as 3b or M2 (40 kilodaltons, Kdal). Plasmid mutants no longer repressing capsular polysaccharide synthesis were either unable to specify the 40 Kdal outer membrane protein a or were deficient in synthesis of 25 Kdal and 14.5 Kdal polypeptides specified by the 2 Mdal DNA fragments. Studies with a minicell-producing strain that also contained a capR mutation indicated that the capR gene product regulated processing of at least one normal protein, the precursor of outer membrane protein a.

Transcriptional control of the calactose operon by the capR (lon) and capT genes.

Mutations in capR or capT cause derepression of the enzymes of the gal operon. The gal-specific messenger ribonucleic acid is directly proportional to the gal enzyme levels in wild type, capR, and capT strains. These results indicate that capR and capT control the gal operon at the transcriptional level.

Cloning of Escherichia coli DNA that controls cell division and capsular polysaccharide synthesis.

A 2 x 10(6) dalton DNA fragment that controls cell division, capsular polysaccharide synthesis, and enzymes of capsular polysaccharide synthesis has been cloned.