El espacio supracoroideo en pacientes afectados por retinosis pigmentaria / The suprachoroidal space in patients affected by retinitis pigmentosa

Antecedentes y objetivo: El espacio supracoroideo (SCS) es una estructura teórica que se sitúa entre el borde interno de la esclera y el límite externo del coroides. El SCS está siendo estudiado por sus posibles usos como vía para la administración de medicamentos y por técnicas quirúrgicas innovadoras para el tratamiento de muchas enfermedades retinianas. La retinitis pigmentosa (RP) es un grupo de trastornos hereditarios y progresivos caracterizados por el detrimento gradual de fotorreceptores que conduce a una discapacidad visual que se manifiesta típicamente como hemeralopía y pérdida progresiva del campo visual. El objetivo del estudio fue definir la morfología de los márgenes coroideos externos mediante el uso de tomografía de coherencia óptica de barrido (SS-OCT) en la RP.Materiales y métodosEstudio observacional retrospectivo diseñado para evaluar la presencia del ESC en la RP. Realizamos SS-OCT en un grupo de 55 pacientes afectados por RP (26 hombres y 29 mujeres, 110 ojos) con una edad media de 51,8±13,7 años. En el grupo de control incluimos a 28 sujetos sanos (6 hombres y 22 mujeres, 56 ojos) con una edad media de 48,8±16,6 años.ResultadosLas imágenes OCT permitieron delinear de manera precisa el margen coroideo externo y el margen escleral interno en los 110 ojos. En el grupo RP se detectó el ESC en 47 de los 110 ojos (42,7%), en el grupo de control se detectó el ESC en 11 ojos (19,6%).Los sujetos del grupo RP con SCS visibles presentaron un menor grosor retiniano (168,4 micrones) en comparación con aquellos con SCS visibles (211,2 micrones, p=0,007). (AU)

Background and objective: The suprachoroidal space (SCS) is a theoretical structure which can be demonstrated between the inner border of the sclera and the outer boundary of the choroid. SCS is being studied for its potential uses as a route for drug delivery and innovative surgical techniques for the treatment of many retinal diseases. Retinitis pigmentosa (RP) is a group of inherited eye disorders characterized by a gradual loss of photoreceptors, resulting in vision impairment, which typically presents as night blindness and progressive visual field loss. The purpose of the study is to define the morphology of outer choroidal margins by means of SS-OCT in RP.Material and methodThis is a retrospective observational study designed to evaluate the presence of SCS in RP. We performed swept source optical coherence tomography (SS-OCT) in a group of 55 patients affected by RP (26 males and 29 females, 110 eyes) with a mean age of 51.8±13.7 years. In the control group, we included 28 healthy subjects (6 males and 22 females, 56 eyes) with a mean age of 48.8±16.6 years.ResultsOCT scans allowed the outer choroidal margin and inner scleral margin to be delineated with certainty in all 110 eyes. In the RP group SCS was detected in 47 of 110 eyes (42.7%), in the control group SCS was detected in 11 eyes (19.6%).Subjects with SCS visible (RP group) had reduced retinal thickness (168.4μm) compared to those with not visible SCS (211.2μm, p=0.007). (AU)

The suprachoroidal space in patients affected by retinitis pigmentosa.

BACKGROUND AND OBJECTIVE: The Suprachoroidal Space (SCS) is a theoretical structure which can be demonstrated between the inner border of the sclera and the outer boundary of the choroid. SCS is being studied for its potential uses as a route for drug delivery and innovative surgical techniques for the treatment of many retinal diseases. Retinitis pigmentosa (RP) is a group of inherited eye disorders characterized by a gradual loss of photoreceptors, resulting in vision impairment, which typically presents as night blindness and progressive visual field loss. The purpose of the study is to define the morphology of outer choroidal margins by means of SS-OCT in RP. MATERIAL AND METHOD: This is a retrospective observational study designed to evaluate the presence of SCS in RP. We performed Swept Source optical coherence tomography (SS-OCT) in a group of 55 patients affected by RP (26 males and 29 females, 110 eyes) with a mean age of 51.8 ±â€¯13.7 years. In the control group, we included 28 healthy subjects (6 males and 22 females, 56 eyes) with a mean age of 48,8 ±â€¯16,6 years. RESULTS: OCT scans allowed the outer choroidal margin and inner scleral margin to be delineated with certainty in all 110 eyes. In the RP group SCS was detected in 47 of 110 eyes (42,7%), in the control group SCS was detected in 11 eyes (19,6%). Subjects with SCS visible (RP group) had reduced retinal thickness (168.4 µm) compared to those with not visible SCL (211.2 µm, P = .007). CONCLUSIONS: SS-OCT can be successfully applied to assess the presence of SCS in RP and the high rate of SCS found in the RP patients is encouraging when considering future innovative therapies.

Effective pair-interaction of phase singularities in random waves.

In two-dimensional random waves, phase singularities are point-like dislocations with a behavior reminiscent of interacting particles. This-qualitative-consideration stems from the spatial arrangement of these entities, which finds its hallmark in a pair correlation reminiscent of a liquid-like system. Starting from their pair correlation function, we derive an effective pair-interaction for phase singularities in random waves by using a reverse Monte Carlo method. This study initiates a new, to the best of our knowledge, approach for the treatment of singularities in random waves and can be generalized to topological defects in any system.

Poynting singularities in the transverse flow-field of random vector waves.

In order to utilize the full potential of tailored flows of electromagnetic energy at the nanoscale, we need to understand its general behavior given by its generic representation of interfering random waves. For applications in on-chip photonics as well as particle trapping, it is important to discern between the topological features in the flow-field of the commonly investigated cases of fully vectorial light fields and their 2D equivalents. We demonstrate the distinct difference between these cases in both the allowed topology of the flow-field and the spatial distribution of its singularities, given by their pair correlation function g(r). Specifically, we show that a random field confined to a 2D plane has a divergence-free flow-field and exhibits a liquid-like correlation, whereas its freely propagating counterpart has no clear correlation and features a transverse flow-field with the full range of possible 2D topologies around its singularities.

Changes in brain activity following the voluntary control of empathy.

In neuroscience, empathy is often conceived as relatively automatic. The voluntary control that people can exert on brain mechanisms that map the emotions of others onto our own emotions has received comparatively less attention. Here, we therefore measured brain activity while participants watched emotional Hollywood movies under two different instructions: to rate the main characters' emotions by empathizing with them, or to do so while keeping a detached perspective. We found that participants yielded highly consistent and similar ratings of emotions under both conditions. Using intersubject correlation-based analyses we found that, when encouraged to empathize, participants' brain activity in limbic (including cingulate and putamen) and somatomotor regions (including premotor, SI and SII) synchronized more during the movie than when encouraged to detach. Using intersubject functional connectivity we found that comparing the empathic and detached perspectives revealed widespread increases in functional connectivity between large scale networks. Our findings contribute to the increasing awareness that we have voluntary control over the neural mechanisms through which we process the emotions of others.

Congenital chylothorax: Current evidence-based prenatal and post-natal diagnosis and management.

Congenital chylothorax is an uncommon condition but represents the main cause of congenital pleural effusion during the neonatal period. It usually appears before birth, both as an isolated disorder or in association with hydrops fetalis, negatively affecting the subsequent neonatal outcome. Prenatal treatment is usually considered to ensure a satisfactory lung development in case of moderate to severe pleural effusion or in the presence of hydrops, although consensus on treatment timing and modalities has not been reached to date. Both medical and surgical therapeutic strategies are available to treat this condition and novel treatment options have been recently attempted with acceptable results in both prenatal and post-natal setting. The heterogeneous clinical presentation of congenital chylothorax together with its rarity, its numerous etiologies and the absence of a highly effective treatment renders the diagnostic and therapeutic approach difficult to standardize. In addition, adequate visualization of the lymphatic system is complex, especially in small neonates, although new promising techniques have been developed lately and may contribute to improved management of this serious but infrequent condition. This review focuses on the current evidence base for the diagnosis and treatment options for congenital chylothorax, suggesting a rational diagnostic and therapeutic approach both in the prenatal and in the neonatal period.

Early fetal hydropic changes are associated with moderate dilatation of the brain ventricular system: A clue to a possible link between cervical lymphatic engorgement and ventricular dilatation?

The aim of this study is to assess whether early cervical lymphatic obstruction is associated with a sonographically detectable dilatation of the ventricular system in the 1st trimester of pregnancy. In particular, the objective is to assess whether fetuses with non-immune hydrops fetalis (NIHF), cystic hygroma, or enlarged nuchal translucency (NT) have a greater atrial width/biparietal diameter (AW/BPD) ratio than normal at time of the combined first trimester screening scan. This retrospective study included 96 first trimester fetuses (33 normal and 63 with various degree of cervical lymphatic engorgement). Inclusion criteria were CRL in the 45-84 mm range and availability of one or more three-dimensional volume datasets of the fetal head, acquired from the BPD plane. Each three-dimensional volume dataset was opened and multiplanar correlation employed to align the three orthogonal planes. The ratio between the atrial width and the BPD (AW/BPD ratio) was used to evaluate the possible presence of increased amount of cerebrospinal fluid. Abnormal cases were placed into 4 categories: 1) enlarged non-septated NT 2.5-3.9 mm, no hydrops; 2) grossly enlarged non-septated NT / edema >3.9 mm; 3) cystic hygroma and/ or NIHF; 4) major anomalies with NT <2.5 mm. Presence of dilatation of the laterocervical jugular lymphatic sacs, karyotype and presence of congenital anomalies were also recorded. The One-way ANOVA test was used to compare means. Intra- and inter-observer variability were also assessed. The AW/BPD ratio was found to be significantly higher in fetuses with grossly enlarged NT/nuchal edema and NIHF/septated cystic hygroma than in normal (p <0.05 and p <0.01, respectively). Also, the AW/BPD ratio was significantly higher in NIHF/septated cystic hygroma than in enlarged NT 2.5-3.9 mm (p <0.05). In case of enlarged NT (2.5-3.9 mm), the AW/BPD ratio is significantly higher in presence of JLS (p <0.01). At the end of the first trimester, presence of cervical lymphatic engorgement, in terms of grossly enlarged NT, nuchal edema, septated cystic hygroma, and NIHF, is statistically associated with a moderate dilatation of the ventricular system. Of note, among fetuses with moderately enlarged NT, those with evidence of dilatation of the JLS show a statistically significant increase in the AW/BPD ratio.

Screening and fluctuation of the topological charge in random wave fields.

Vortices, phase singularities, and topological defects of any kind often reflect information that is crucial for understanding physical systems in which such entities arise. With near-field experiments supported by numerical calculations, we determine the fluctuations of the topological charge for phase singularities in isotropic random waves as a function of the size R of the observation window. We demonstrate that for two-dimensional fields such fluctuations increase with a superlinear scaling law, consistent with a R log R behavior. Additionally, we show that such scaling remains valid in the presence of anisotropy.

Report of final results regarding brain and heart tumors in Sprague-Dawley rats exposed from prenatal life until natural death to mobile phone radiofrequency field representative of a 1.8 GHz GSM base station environmental emission.

BACKGROUND: In 2011, IARC classified radiofrequency radiation (RFR) as possible human carcinogen (Group 2B). According to IARC, animals studies, as well as epidemiological ones, showed limited evidence of carcinogenicity. In 2016, the NTP published the first results of its long-term bioassays on near field RFR, reporting increased incidence of malignant glial tumors of the brain and heart Schwannoma in rats exposed to GSM - and CDMA - modulated cell phone RFR. The tumors observed in the NTP study are of the type similar to the ones observed in some epidemiological studies of cell phone users. OBJECTIVES: The Ramazzini Institute (RI) performed a life-span carcinogenic study on Sprague-Dawley rats to evaluate the carcinogenic effects of RFR in the situation of far field, reproducing the environmental exposure to RFR generated by 1.8 GHz GSM antenna of the radio base stations of mobile phone. This is the largest long-term study ever performed in rats on the health effects of RFR, including 2448 animals. In this article, we reported the final results regarding brain and heart tumors. METHODS: Male and female Sprague-Dawley rats were exposed from prenatal life until natural death to a 1.8 GHz GSM far field of 0, 5, 25, 50 V/m with a whole-body exposure for 19 h/day. RESULTS: A statistically significant increase in the incidence of heart Schwannomas was observed in treated male rats at the highest dose (50 V/m). Furthermore, an increase in the incidence of heart Schwann cells hyperplasia was observed in treated male and female rats at the highest dose (50 V/m), although this was not statistically significant. An increase in the incidence of malignant glial tumors was observed in treated female rats at the highest dose (50 V/m), although not statistically significant. CONCLUSIONS: The RI findings on far field exposure to RFR are consistent with and reinforce the results of the NTP study on near field exposure, as both reported an increase in the incidence of tumors of the brain and heart in RFR-exposed Sprague-Dawley rats. These tumors are of the same histotype of those observed in some epidemiological studies on cell phone users. These experimental studies provide sufficient evidence to call for the re-evaluation of IARC conclusions regarding the carcinogenic potential of RFR in humans.

Results of lifespan exposure to continuous and intermittent extremely low frequency electromagnetic fields (ELFEMF) administered alone to Sprague Dawley rats.

BACKGROUND: Up to now, experimental studies on rodents have failed to provide definitive confirmation of the carcinogenicity of extremely low frequency electromagnetic fields (ELFEMF). Two recent studies performed in our laboratory on Sprague-Dawley rats reported a statistically significant increase in malignant tumors of different sites (mammary gland, C-cells carcinoma, hemolymphoreticular neoplasia, and malignant heart Schwannoma) when ELFEMF exposure was associated with exposure to formaldehyde (50 mg/l) or acute low dose of γ-radiation (0.1 Gy) (Soffritti et al., 2016a) (Soffritti et al., 2016b). The same doses of known carcinogenic agents (50 mg/l formaldehyde, or acute 0.1 Gy γ-radiation), when administered alone, previously failed to induce any statistically significant increase in the incidence of total and specific malignant tumors in rats of the same colony. OBJECTIVES: A lifespan whole-body exposure study was conducted to evaluate the possible carcinogenic effects of ELFEMF exposure administered alone to Sprague-Dawley rats, as part of the integrated project of the Ramazzini Institute (RI) for studying the effects on health of ELFEMF alone or in combination with other known carcinogens. METHODS: Male and female Sprague-Dawley rats were exposed 19 h/day to continuous sinusoidal-50 Hz magnetic fields (S-50 Hz MF) at flux densities of 0 (control group), 2, 20, 100 or 1000µT, and to intermittent (30 min on/30 min off) S-50 Hz MF at 1000 µT, from prenatal life until natural death. RESULTS: Survival and body weight trends in all groups of rats exposed to ELFEMF were comparable to those found in sex-matched controls. The incidence and number of malignant and benign tumors was similar in all groups. Magnetic field exposure did not significantly increase the incidence of neoplasias in any organ, including those sites that have been identified as possible targets in epidemiological studies (leukemia, breast cancer, and brain cancer). CONCLUSIONS: Life-span exposures to continuous and intermittent sinusoidal-50 Hz ELFEMFs, when administered alone, did not represent a significant risk factor for neoplastic development in our experimental rat model. In light of our previous results on the carcinogenic effects of ELFEMF in combination with formaldehyde and γ-radiation, further experiments are necessary to elucidate the possible role of ELFEMF as cancer enhancer in presence of other chemical and physical carcinogens.

Brain lymphatic drainage system in fetus and newborn: Birth of a new era of exploration.

A peculiar brain lymphatic drainage system has been recently fully recognized in animals and humans. It comprises different draining pathways, including the lymphatic system, the perivascular drainage pathway, and the cerebrospinal fluid (CSF) drainage routes. Although scant data are available about its function during the neonatal period, it may play a role in neonatal brain diseases. In this review, we focus on the actual knowledge of brain lymphatic drainage system, and we hypothesize potential implications of its impairment and dysfunction in major neonatal neurological diseases.

Persistence and Lifelong Fidelity of Phase Singularities in Optical Random Waves.

Phase singularities are locations where light is twisted like a corkscrew, with positive or negative topological charge depending on the twisting direction. Among the multitude of singularities arising in random wave fields, some can be found at the same location, but only when they exhibit opposite topological charge, which results in their mutual annihilation. New pairs can be created as well. With near-field experiments supported by theory and numerical simulations, we study the persistence and pairing statistics of phase singularities in random optical fields as a function of the excitation wavelength. We demonstrate how such entities can encrypt fundamental properties of the random fields in which they arise.

Application of fluence field modulation to proton computed tomography for proton therapy imaging.

This simulation study presents the application of fluence field modulated computed tomography, initially developed for x-ray CT, to proton computed tomography (pCT). By using pencil beam (PB) scanning, fluence modulated pCT (FMpCT) may achieve variable image quality in a pCT image and imaging dose reduction. Three virtual phantoms, a uniform cylinder and two patients, were studied using Monte Carlo simulations of an ideal list-mode pCT scanner. Regions of interest (ROI) were selected for high image quality and only PBs intercepting them preserved full fluence (FF). Image quality was investigated in terms of accuracy (mean) and noise (standard deviation) of the reconstructed proton relative stopping power compared to reference values. Dose calculation accuracy on FMpCT images was evaluated in terms of dose volume histograms (DVH), range difference (RD) for beam-eye-view (BEV) dose profiles and gamma evaluation. Pseudo FMpCT scans were created from broad beam experimental data acquired with a list-mode pCT prototype. FMpCT noise in ROIs was equivalent to FF images and accuracy better than -1.3%(-0.7%) by using 1% of FF for the cylinder (patients). Integral imaging dose reduction of 37% and 56% was achieved for the two patients for that level of modulation. Corresponding DVHs from proton dose calculation on FMpCT images agreed to those from reference images and 96% of BEV profiles had RD below 2 mm, compared to only 1% for uniform 1% of FF. Gamma pass rates (2%, 2 mm) were 98% for FMpCT while for uniform 1% of FF they were as low as 59%. Applying FMpCT to preliminary experimental data showed that low noise levels and accuracy could be preserved in a ROI, down to 30% modulation. We have shown, using both virtual and experimental pCT scans, that FMpCT is potentially feasible and may allow a means of imaging dose reduction for a pCT scanner operating in PB scanning mode. This may be of particular importance to proton therapy given the low integral dose found outside the target.

Spatial Distribution of Phase Singularities in Optical Random Vector Waves.

Phase singularities are dislocations widely studied in optical fields as well as in other areas of physics. With experiment and theory we show that the vectorial nature of light affects the spatial distribution of phase singularities in random light fields. While in scalar random waves phase singularities exhibit spatial distributions reminiscent of particles in isotropic liquids, in vector fields their distribution for the different vector components becomes anisotropic due to the direct relation between propagation and field direction. By incorporating this relation in the theory for scalar fields by Berry and Dennis [Proc. R. Soc. A 456, 2059 (2000)], we quantitatively describe our experiments.

Adolescents and young adults with type 1 diabetes display a high prevalence of endothelial dysfunction.

AIM: Little is known about endothelial function in adolescents with type 1 diabetes, and we evaluated endothelial dysfunction, using reactive hyperaemia peripheral arterial tonometry (RH-PAT). METHODS: This prospective, observational, 1-year study focused on 73 adolescents with type 1 diabetes, using multiple daily injections or continuous subcutaneous insulin infusion. The subjects were assessed using RH-PAT, body mass index, blood pressure, fasting lipid profile, glycated haemoglobin, insulin requirements and hours of physical exercise per week. RESULTS: Endothelial dysfunction was observed in 56 patients (76.7%), with lower mean RH-PAT scores (1.26 ± 0.22 versus 2.24 ± 0.48, p < 0.0001) and higher glycated haemoglobin values at baseline (8.27 ± 1.24% versus 7.37 ± 0.54%, p = 0.006) and as a mean of the whole period since diagnosis (8.25 ± 1.22% versus 7.72 ± 0.82%, p = 0.034). A higher percentage of patients with endothelial dysfunction showed abnormal cardiac autonomic tests (p = 0.02) and were more sedentary, exercising <4 hours a week, than patients with normal endothelial function. After follow-up in 64/73 patients, we observed endothelial dysfunction in 81.8% of patients, despite a modest improvement in glycated haemoglobin. CONCLUSION: Adolescents with type 1 diabetes displayed evidence of endothelial dysfunction. Good metabolic control (glycated haemoglobin ≤7.5%, 58 mmol/mol) and regular physical activity of at least 4 h a week might be protective.

Explant-derived human dental pulp stem cells enhance differentiation and proliferation potentials.

Numerous stem cell niches are present in the different tissues and organs of the adult human body. Among these tissues, dental pulp, entrapped within the 'sealed niche' of the pulp chamber, is an extremely rich site for collecting stem cells. In this study, we demonstrate that the isolation of human dental pulp stem cells by the explants culture method (hD-DPSCs) allows the recovery of a population of dental mesenchymal stem cells that exhibit an elevated proliferation potential. Moreover, we highlight that hD-DPSCs are not only capable of differentiating into osteoblasts and chondrocytes but are also able to switch their genetic programme when co-cultured with murine myoblasts. High levels of MyoD expression were detected, indicating that muscle-specific genes in dental pulp cells can be turned on through myogenic fusion, confirming thus their multipotency. A perivascular niche may be the potential source of hD-DPSCs, as suggested by the consistent Ca(2+) release from these cells in response to endothelin-1 (ET-1) treatment, which is also able to significantly increase cell proliferation. Moreover, response to ET-1 has been found to be superior in hD-DPSCs than in DPSCs, probably due to the isolation method that promotes release of stem/progenitor cells from perivascular structures. The ability to isolate, expand and direct the differentiation of hD-DPSCs into several lineages, mainly towards myogenesis, offers an opportunity for the study of events associated with cell commitment and differentiation. Therefore, hD-DPSCs display enhanced differentiation abilities when compared to DPSCs, and this might be of relevance for their use in therapy.

Marine macroalgae as sources of polyunsaturated fatty acids.

Algae from cold water (Canada) and warm water (China) were analysed for the total lipid content, and for their fatty acid (FA) composition and content. The major findings are that fatty acids (FA) from Canadian algae are generally richer in polyunsaturated FA (PUFA), with a higher n-3/n-6 FA ratio, and a higher degree of total unsaturation. The C 18:4 FA (stearidonic acid, morotic acid as synonym) was detected in greater amounts in cold water samples. The high levels of total PUFA, and especially of n-3 FA in Canadian algae, suggests possible utilization for nutritional purposes.

Ultrastructural investigations on protective effects of NCX 4016 (nitroaspirin) on macrovascular endothelium in diabetic Wistar rats.

The effect of a nitric oxide-donating aspirin derivative, 2-acetoxy-benzoate 3-(nitroxy-methyl)phenyl ester (NCX 4016), and aspirin on the aortic endothelium of diabetic rats was investigated by using scanning and transmission electron microscopy. Control and streptozotocin-treated rats were used. Metabolic control was assessed by measuring blood and urine metabolites, and 24-h urine volume. The ultrastructural study was performed after 7 weeks of diabetes and 6 weeks of therapy. Streptozotocin treatment induced a persistent hyperglycemia which was not influenced by the pharmacological treatments. Values of blood metabolites were in line with the diabetic status. Both scanning and transmission electron microscopy revealed that aortic endothelium was severely damaged in all diabetic rats except for the NCX 4016 treated ones. Our data document the protective effects of NCX 4016 on the vascular endothelium of diabetic rats. Since aspirin had no protective action, NCX 4016 may have exerted its beneficial action by releasing nitric oxide.

Marine macroalgae analyzed by mass spectrometry are rich sources of polyunsaturated fatty acids.

Algae from cold water (Canada) and warm water (China) were analyzed for their total lipid content, and for their fatty acid (FA) composition and content. The major findings are that FA from Canadian algae are generally richer in polyunsaturated FA (PUFA), with a higher n-3/n-6 FA ratio, and a higher degree of total unsaturation. The 18 C, 4 double bonds FA (18 : 4 stearidonic acid, morotic acid as synonym) was detected in greater amounts in cold water samples. The high levels of total PUFA, and especially of n-3 FA in Canadian algae, suggests their possible utilizations for nutritional purposes.

Role of interaction between variants in the PPARG and interleukin-6 genes on obesity related metabolic risk factors.

The combined effect of Peroxisome proliferator-activated receptor gamma (PPARG) Pro/Ala and interleukin-6 G174C gene variants, was evaluated in 429 Caucasian subjects in order to determine whether subjects carrying both variants were at different risk for obesity. In particular, the combined contribution of these two variants (both independent and interaction effects) to the total variation of obesity-related factors was estimated. All subjects were genotyped for codon 12 Pro/Ala locus variability and for the interleukin-6-174 C/G promoter polymorphism. Subjects with the Ala variant had significantly lower BMI, insulin resistance, triglyceride levels than those without. Furthermore, subjects with Ala variant had significantly lower IL-6 levels (0.88 +/- 0.9 vs 1.61 +/- 2.25 pg/ml; p = 0.041). In contrast, the IL6-C variant was significantly associated with lower plasma IL-6 and with lower total cholesterol levels but was not significantly associated with any other obesity risk factors. Indeed, subjects carrying both PPARG and IL-6 gene variants, had a clearly more favourable profile of obesity related risk factors than subjects with one variant, having Ala+/C+ carriers lower BMI (22.8 +/- 2.3 vs 24.14 +/- 1.9; f = 5.31; p < 0.005), insulin resistance (1.49 +/- 0.70 vs 2.13 +/- 0.92; f = 4.342; p = 0.038) and triglyceride levels (79.15 +/- 32.9 vs 98 +/- 6.73 mg/dl; f = 3.120; p < 0.005). These findings suggest that the effect of the two genetic variants on 'obesity related' factors is additive.