Reproducibility and within-day variability of body fat measurements using segmental bipolar bioelectrical impedance in women

BACKGROUND AND AIMS: little is known regarding the reproducibility of body fat measuring devices; hence, we assessed the between and within-device reproducibility, and the within-day variability of body fat measurements. METHODS: body fat percentage was measured twice on seventeen female students aged between 18 and 20 with a body mass index of 21.9 ± 2.5 kg/m2 (mean ± SD) using seven bipolar bioelectrical impedance devices. Each participant was also measured each hour between 7:00 and 22:00. RESULTS: the correlation between first and second measurements was very high (Spearman r between 0.985 and 1.000, p<0.001), as well as between devices (Spearman r between 0.916 and 0.991, p<0.001). Repeated measurements analysis showed no differences were between devices (p=0.59) or readings (first vs. second: p=0.74). Conversely, significant differences were found between assessment periods throughout the day, measurements made in the morning being lower than those made in the afternoon (F test for repeated values= 6.58, p<0.001). CONCLUSIONS: the between and within-device reproducibility for measuring body fat is high, enabling the use of multiple devices in a single study. Conversely, small but significant changes in body fat measurements occur during the day, urging body fat measurements to be performed at fixed times.

Water-filtered infrared-A radiation (wIRA) is not implicated in cellular degeneration of human skin

Rapport de synthèse : Introduction : le vieillissement cutané est un processus biologique complexe auquel participe une exposition excessive au rayonnement ultraviolet du soleil. En particulier, les longueurs d'onde des rayons ultraviolets A et B (UV-A et UV-B) peuvent induire une augmentation de la synthèse de protéases, comme la métalloprotéinase matricielle 1 (MMP-1), qui est impliquée dans le processus de vieillissement. La thermothérapie par infrarouges, dont les longueurs d'onde sont plus longues que celles des UV, est largement utilisée à des fins thérapeutiques ou cosmétiques. Or, il a été démontré que les infrarouges en filtration aqueuse (IRFA) pouvaient induire une augmentation de la production de MMP-1 et par conséquent être nocifs. Il serait donc intéressant d'évaluer les effets des IRFA au niveau cellulaire et moléculaire. But Expérimental : étudier les effets des lampes à infrarouges en filtration aqueuse utilisées en clinique sur des fibroblastes cutanés humains en culture, afin d'analyser l'expression du gène codant pour la protéine MMP-1. Méthode : des fibroblastes cutanés humain ont été irradiés d'une part avec approximativement 88% d'IRFA (780-1400 nm) et 12% de lumière rouge (LR, 665-780 nm) avec 380 mW/cm2 IRFA(+LR) (333 mW/cm2 IRFA) et d'autre part avec des UV-A comme contrôle. Des courbes de survie cellulaire ont été établies après une exposition allant de 15 minutes à 8 heures au IRFA(+LR) (340-10880 J/cm2 wIRA(+RL), 300-9600 J/cm2 wIRA) ou de 15 à 45 minutes aux UV-A(+BL) (25-75 J/cm2 UV-A(+BL). L'induction de l'ARNm du gène de la MMP-1 a été analysé dans les fibroblastes cutanés humain à deux températures physiologiques (30°C et 37°C) lors d'expositions uniques de 15 à 60 minutes aux IRFA(+LR) (340-1360 J/cm2 IRFA(+LR), 300-1200 J/cm2 IRFA) ou de 30 minutes aux UV-A(+BL) (50 J/cm2 UVA(+BL)). De plus, nous avons effectué des irradiations répétées, une a chaque passage cellulaire jusqu'au passage. 10 de 15 minutes d'IRFA(+LR) 340 J/cm2 IRFA(+LR), 300 J/cm2 IRFA) . Résultats : une exposition unique aux UV-A (+BL) entraîne chez des fibroblastes cutanés humains une augmentation de la mort cellulaire, ainsi qu'une forte augmentation de l'expression du gène codant pour la MMP-1. L'augmentation mise en évidence pour cet ARNm varie en fonction de la technique utilisée : elle est de 11 ± 1 fois par RT-PCR classique, de 76 ± 2 fois par RT-PCR quantitative à 30°C, et de 75 ± 1 fois par RT-PCR quantitative à 37°C. Par contre, une exposition unique ou répétée aux IRFA (+LR) n'induit aucune augmentation de la mort cellulaire, ni de l'expression de l'ARNm de la MMP-1 chez ces fibroblastes. Conclusions : les résultats de cette étude montrent que, contrairement aux rayons ultraviolets, les IRFA (+LR) ne semblent impliqués ni dans le vieillissement, ni dans la mort cellulaire, même utilisés à des doses très élevées. Ces résultats sont en accord avec certaines investigations in vivo montrant une induction de MMP-1 par des UV et non des infrarouges. Ces dernières études suggèrent d'ailleurs plutôt un rôle protecteur des IRFA (+LR).

Evaluation des modifications anatomiques et fonctionnelles de la macula après chirurgie des membranes néovasculaires rétrofovéolaires dans la dégénérescence maculaire liée à l'âge [Evaluation of functional and anatomical changes in the macula after surgery for retro-foveal neovascularization of membranes in age-related macular degeneration].

PURPOSE: The aim of this study was to evaluate the direct effect of surgical treatment of subfoveolar neovascular membranes in age related macular degeneration to macular functions. PATIENTS AND METHODS: Thirteen eyes of 13 patients were included in this study. Macular function was assayed by visual acuity and central visual field using the Octopus perimeter before surgery and in the first three post operative months. Pre and post operative fluorescein angiography frames were digitalized and the size of each lesions were compared. RESULTS: After a 3 months follow up, visual acuity remained stable or improved in 66% of the patients. However, visual acuity was better than 0.1 in 15% of the patients. Central visual field comparison disclosed a significant worsening of the retinal sensitivity in the 3 degree field surrounding the central point. On fluorescein frames, submacular scar was 141% of the size of the neovascular membrane. After a mean follow up of 6.9 months (range 3-14), one case of recurrence occurred. A cataract was observed in 85% of the phakic patients followed for more than six months. CONCLUSION: After a short term follow up, surgery can stabilise visual acuity, even though it remains poor. A worsening of the scotoma in the 3 degrees surrounding the central point is observed. However, patients noticed a subjective visual improvement in 62% of the case.

Early clinical experience with ranibizumab for occult and minimally classic neovascular membranes in age-related macular degeneration.

BACKGROUND: In large randomized multicenter trials, ranibizumab has shown its therapeutic efficacy for exudative age-related macular degeneration (AMD). The aim of this paper is to report the real-life clinical experience with this treatment for occult and minimally classic membranes without pigment epithelium detachment. METHODS: We conducted a retrospective chart review of 37 patients with occult and minimally classic neovascular membranes in AMD, without pigment epithelium detachment. RESULTS: The mean visual improvement of 2 lines at 3, 6 and 9 months corresponds well with the results of the large trials. A mean number of 5 reinjections was reached by month 8. It may potentially exceed the mean 5.5 injections of the PrONTO study (prospective optical coherence tomography imaging of patients with neovascular AMD treated with intraocular ranibizumab). At months 6-8 recurrence was frequently observed. CONCLUSION: The early experience of ranibizumab in clinical practice brings similarly good results as the large-scale trials. However, interrupting the treatment too early may be a disadvantage.

Segmental body composition assessed by bioelectrical impedance analysis and DEXA in humans.

The present study assessed the relative contribution of each body segment to whole body fat-free mass (FFM) and impedance and explored the use of segmental bioelectrical impedance analysis to estimate segmental tissue composition. Multiple frequencies of whole body and segmental impedances were measured in 51 normal and overweight women. Segmental tissue composition was independently assessed by dual-energy X-ray absorptiometry. The sum of the segmental impedance values corresponded to the whole body value (100.5 +/- 1.9% at 50 kHz). The arms and legs contributed to 47.6 and 43.0%, respectively, of whole body impedance at 50 kHz, whereas they represented only 10.6 and 34.8% of total FFM, as determined by dual-energy X-ray absorptiometry. The trunk averaged 10.0% of total impedance but represented 48.2% of FFM. For each segment, there was an excellent correlation between the specific impedance index (length2/impedance) and FFM (r = 0.55, 0.62, and 0.64 for arm, trunk, and leg, respectively). The specific resistivity was in a similar range for the limbs (159 +/- 23 cm for the arm and 193 +/- 39 cm for the leg at 50 kHz) but was higher for the trunk (457 +/- 71 cm). This study shows the potential interest of segmental body composition by bioelectrical impedance analysis and provides specific segmental body composition equations for use in normal and overweight women.

Allelic variation in the VMD2 gene in best disease and age-related macular degeneration.

PURPOSE: To assess the allelic variation of the VMD2 gene in patients with Best disease and age-related macular degeneration (AMD). METHODS: Three hundred twenty-one AMD patients, 192 ethnically similar control subjects, 39 unrelated probands with familial Best disease, and 57 unrelated probands with the ophthalmoscopic findings of Best disease but no family history were screened for sequence variations in the VMD2 gene by single-strand conformation polymorphism (SSCP) analysis. Amplimers showing a bandshift were reamplified and sequenced bidirectionally. In addition, the coding regions of the VMD2 gene were completely sequenced in six probands with familial Best disease who showed no SSCP shift. RESULTS: Forty different probable or possible disease-causing mutations were found in one or more Best disease or AMD patients. Twenty-nine of these variations are novel. Of the 39 probands with familial Best disease, mutations were detected in all 39 (33 by SSCP and 6 by DNA sequencing). SSCP screening of the 57 probands with a clinical diagnosis of Best disease but no family history revealed 16 with mutations. Mutations were found in 5 of 321 AMD patients (1.5%), a fraction that was not significantly greater than in control individuals (0/192, 0%). CONCLUSIONS: Patients with the clinical diagnosis of Best disease are significantly more likely to have a mutation in the VMD2 gene if they also have a positive family history. These findings suggest that a small fraction of patients with the clinical diagnosis of AMD may actually have a late-onset variant of Best disease, whereas at the same time, a considerable fraction of isolated patients with the ophthalmoscopic features of Best disease are probably affected with some other macular disease.

Genotype-phenotype correlation of age-related macular degeneration : influence of complement factor H polymorphism

RAPPORT DE SYNTHESE La dégénérescence maculaire liée à l'âge (DMLA) est une maladie très fréquente qui représente la cause principale de cécité légale chez les sujets de plus de 50 ans en Occident. Bien que l'étiologie exacte de cette affection ne soit pas complètement connue, des facteurs environnementaux et génétiques influencent sa survenue et son évolution. A ce sujet, de récentes recherches ont notamment montré une association marquée à une variante du gène CFH, Y402H. Nous ignorons toutefois si le polymorphisme Y402H est associé à un phénotype particulier de la maladie. Cette étude a pour but d'établir si cette variante du gène CFH est associée à certaines caractéristiques phénotypiques précoces. L'étude porte sur quatre cent vingt patients atteints de DMLA qui ont été phénotypés sur la base de photographie du fond d'oeil (International Classification and Grading system for age- related macular degeneration) et génotypés à partir d'ADN leucocytaire à la recherche de la variante Y402H du gène CFH. Ces données ont ensuite fait l'objet d'une analyse statistique de l'association génotype-phénotype (le génotype de 50 sujets-contrôle a été utilisé pour confirmer l'association du polymorphisme avec la DMLA). Les résultats obtenus, corrigés pour l'âge et le sexe, montrent un odds ratio (OR) de développer une DMLA de 2.95 en présence d'au moins un allèle à risque C et de 9.05 pour les homozygotes CC. Par contre, aucune influence n'est observée sur les stades de la maladie (précoce-tardif)? Une association significative entre le génotype CC et la présence de druses périphériques (p=0.028), ainsi que la localisation centrale des druses (p=0,049) a été mise en évidence. Aucune autre tendance n'a été dégagée concernant les critères restants (taille, surface totale recouverte, localisation nasale des druses) ou les changements pigmentaires. Cette étude a permis de confirmer l'association entre la variante Y4G2H et la DMLA dans la population suisse et de conclure que la variante Y402H du gène CFH présente une association géno-phénotypique pour certaines caractéristiques des druses. Il est probable que d'autres facteurs génétiques encore influencent le phénotype de la DMLA. De nouvelles recherches seront nécessaires pour préciser l'influence de ces autres facteurs génétiques ou environnementaux, en vue d'une meilleure compréhension de la pathogenèse de cette affection, et pour développer des mesures thérapeutiques et prophylactiques adaptées.

Characteristics of eyes with secondary loss of visual acuity receiving variable dosing ranibizumab for neovascular age-related macular degeneration.

PURPOSE: The aim of this work is to investigate the characteristics of eyes failing to maintain visual acuity (VA) receiving variable dosing ranibizumab for neovascular age-related macular degeneration (nAMD) after three initial loading doses. METHODS: A consecutive series of patients with nAMD, who, after three loading doses of intravitreal ranibizumab (0.5 mg each), were re-treated for fluid seen on optical coherence tomography. After exclusion of eyes with previous treatment, follow-up less than 12 months, or missed visits, 99 patients were included in the analysis. The influence of baseline characteristics, initial VA response, and central retinal thickness (CRT) fluctuations on the VA stability from month 3 to month 24 were analyzed using subgroups and multiple regression analyses. RESULTS: Mean follow-up duration was 21.3 months (range 12-40 months, 32 patients followed-up for ≥24 months). Secondary loss of VA (loss of five letters or more) after month 3 was seen in 30 patients (mean VA improvement from baseline +5.8 letters at month 3, mean loss from baseline -5.3 letters at month 12 and -9.7 at final visit up to month 24), while 69 patients maintained vision (mean gain +8.9 letters at month 3, +10.4 letters at month 12, and +12.8 letters at final visit up to month 24). Secondary loss of VA was associated with the presence of pigment epithelial detachment (PED) at baseline (p 0.01), but not with baseline fibrosis/atrophy/hemorrhage, CRT fluctuations, or initial VA response. Chart analysis revealed additional individual explanations for the secondary loss of VA, including retinal pigment epithelial tears, progressive fibrosis, and atrophy. CONCLUSIONS: Tissue damage due to degeneration of PED, retinal pigment epithelial tears, progressive fibrosis, progressive atrophy, or massive hemorrhage, appears to be relevant in causing secondary loss of VA despite vascular endothelial growth factor suppression. PED at baseline may represent a risk factor.

Reproducibility and within-day variability of body fat masurements using segmental bipolar bioelectrical impedance in women

Objective: to assess the between and within-device reproducibility, as well as within-day variability of body fat measurements. Methods: body fat percentage (%BF) was measured twice on seventeen female students aged between 18 and 20 with a body mass index of 21.9 22.6 kg/m2 (mean SD) using seven bipolar bioelectrical impedance devices (BF-306) according to the manufacturer's recommendations. Each student was also measured each hour between 7:00 and 22:00. Statistical analysis was conducted using a general linear model for repeated measurements. Results: the correlation between first and second measurements was very high (Pearson r between 0.985 and 1.000, p<0.001), as well as the correlation between devices (Pearson r between 0.986 and 0.999, all p<0.001). Repeated measurements analysis showed no differences were between devices (F test=0.83, p=0.59) or readings (first vs. second: F test=0.12, p=0.74). Conversely, significant differences were found between assessment periods throughout the day, measurements made in the morning being lower than those made in the afternoon. Assuming an overall daily average of 100 (based on all measurements), the values were 95.8 3.2 (mean SD) at 8:00 versus 101.3 3.0 at 20:00, corresponding to a mean change of 2.2 1.1 in %BF (F test for repeated values=6.58, p<0.001). Conclusions: the between and within-device reproducibility for measuring body fat is high, enabling the use of multiple devices in a single study. Conversely, small but significant changes in body fat measurements occur during the day, urging body fat measurements to be performed at fixed times.

Age-Related Macular Degeneration: Clinical Findings following Treatment with Antiangiogenic Drugs.

Purpose. To survey the management of patients with neovascular age-related macular degeneration (nvAMD) in Spain. Methods. An observational retrospective multicenter study was conducted. The variables analyzed were sociodemographic characteristics, foveal and macular thickness, visual acuity (VA), type of treatment, number of injections, and the initial administration of a loading dose of an antiangiogenic drug. Results. 208 patients were followed up during 23.4 months in average. During the first and second years, patients received a mean of 4.5 ± 1.8 and 1.6 ± 2.1 injections of antiangiogenic drugs, and 5.4 ± 2.8 and 3.6 ± 2.2 follow-up visits were performed, respectively. The highest improvement in VA was observed at 3 months of follow-up, followed by a decrease in the response that stabilized above baseline values until the end of the study. Patients who received an initial loading dose presented greater VA gains than those without. Conclusions. Our results suggest the need for a more standardized approach in the management and diagnosis of nvAMD receiving VEGF inhibitors. To achieve the visual outcomes reported in pivotal trials, an early diagnosis, proactive approach (more treating than follow-up visits), and a close monitoring might be the key to successfully manage nvAMD.

A delphi study to detect deficiencies and propose actions in real life treatment of neovascular age-related macular degeneration.

Purpose. Spanish retina specialists were surveyed in order to propose actions to decrease deficiencies in real-life neovascular age macular degeneration treatment (nv-AMD). Methods. One hundred experts, members of the Spanish Vitreoretinal Society (SERV), were invited to complete an online survey of 52 statements about nv-AMD management with a modified Delphi methodology. Four rounds were performed using a 5-point Linkert scale. Recommendations were developed after analyzing the differences between the results and the SERV guidelines recommendations. Results. Eighty-seven specialists completed all the Delphi rounds. Once major potential deficiencies in real-life nv-AMD treatment were identified, 15 recommendations were developed with a high level of agreement. Consensus statements to reduce the burden of the disease included the use of treat and extend regimen and to reduce the amount of diagnostic tests during the loading phase and training technical staff to perform these tests and reduce the time between relapse detection and reinjection, as well as establishing patient referral protocols to outside general ophthalmology clinics. Conclusion. The level of agreement with the final recommendations for nv-AMD treatment among Spanish retinal specialist was high indicating that some actions could be applied in order to reduce the deficiencies in real-life nv-AMD treatment.

Light-induced retinal degeneration correlates with changes in iron metabolism gene expression, ferritin level, and aging.

PURPOSE: Retinal degeneration is associated with iron accumulation in several rodent models in which iron-regulating proteins are impaired. Oxidative stress is catalyzed by unbound iron. METHODS: The role of the heavy chain of ferritin, which sequesters iron, in regulating the thickness of the photoreceptor nuclear layer in the 4- and 16-month-old wild-type H ferritin (HFt(+/+)) and heterozygous H ferritin (HFt(+/-)) mice was investigated, before and 12 days after exposure to 13,000-lux light for 24 hours. The regulation of gene expression of the various proteins involved in iron homeostasis, such as transferrin, transferrin receptor, hephaestin, ferroportin, iron regulatory proteins 1 and 2, hepcidin, ceruloplasmin, and heme-oxygenase 1, was analyzed by quantitative (q)RT-PCR during exposure (2, 12, and 24 hours) and 24 hours after 1 day of exposure in the 4-month-old HFt(+/+) and HFt(+/-) mouse retinas. RESULTS: Retinal degeneration in the 4-month-old HFt(+/-) mice was more extensive than in the HFt(+/+) mice. Yet, it was more extensive in both of the 16-month-old mouse groups, revealing the combined effect of age and excessive light. Injury caused by excessive light modified the temporal gene expression of iron-regulating proteins similarly in the HFt(+/-) and HFt(+/+) mice. CONCLUSIONS: Loss of one allele of H ferritin appears to increase light-induced degeneration. This study highlighted that oxidative stress related to light-induced injury is associated with major changes in gene expression of iron metabolism proteins.

Individualized Therapy with Ranibizumab in Wet Age-Related Macular Degeneration.

Individualized treatment regimens may reduce patient burden with satisfactory patient outcomes in neovascular age-related macular degeneration. Intravitreal anti-VEGF drugs are the current gold standard. Fixed monthly injections offer the best visual outcome but this regimen is not commonly followed outside clinical trials. A PRN regimen requires monthly visits where the patient is treated in the presence of signs of lesion activity. Therefore, an early detection of reactivation of the disease with immediate retreatment is crucial to prevent visual acuity loss. Several trials suggest that "treat and extend" and other proactive regimens provide a reasonable approach. The rationale of the proactive regimens is to perform treatment anticipating relapses or recurrences and therefore avoid drops in vision while individualizing patient followup. Treat and extend study results in significant direct medical cost savings from fewer treatments and office visits compared to monthly treatment. Current data suggest that, for one year, PRN is less expensive, but treat and extend regimen would likely be less expensive for subsequent years. Once a patient is not a candidate to continue with treatment, he/she should be sent to an outpatient unit with adequate resources to follow nAMD patients in order to reduce the burden of specialized ophthalmologist services.

Hominoid fission of chromosome 14/15 and the role of segmental duplications.

Ape chromosomes homologous to human chromosomes 14 and 15 were generated by a fission event of an ancestral submetacentric chromosome, where the two chromosomes were joined head-to-tail. The hominoid ancestral chromosome most closely resembles the macaque chromosome 7. In this work, we provide insights into the evolution of human chromosomes 14 and 15, performing a comparative study between macaque boundary region 14/15 and the orthologous human regions. We construct a 1.6-Mb contig of macaque BAC clones in the region orthologous to the ancestral hominoid fission site and use it to define the structural changes that occurred on human 14q pericentromeric and 15q subtelomeric regions. We characterize the novel euchromatin-heterochromatin transition region (∼20 Mb) acquired during the neocentromere establishment on chromosome 14, and find it was mainly derived through pericentromeric duplications from ancestral hominoid chromosomes homologous to human 2q14-qter and 10. Further, we show a relationship between evolutionary hotspots and low-copy repeat loci for chromosome 15, revealing a possible role of segmental duplications not only in mediating but also in "stitching" together rearrangement breakpoints.