AGE/RAGE/DIAPH1 axis is associated with immunometabolic markers and risk of insulin resistance in subcutaneous but not omental adipose tissue in human obesity.

BACKGROUND/OBJECTIVES: The incidence of obesity continues to increase worldwide and while the underlying pathogenesis remains largely unknown, nutrient excess, manifested by "Westernization" of the diet and reduced physical activity have been proposed as key contributing factors. Western-style diets, in addition to higher caloric load, are characterized by excess of advanced glycation end products (AGEs), which have been linked to the pathophysiology of obesity and related cardiometabolic disorders. AGEs can be "trapped" in adipose tissue, even in the absence of diabetes, in part due to higher expression of the receptor for AGEs (RAGE) and/or decreased detoxification by the endogenous glyoxalase (GLO) system, where they may promote insulin resistance. It is unknown whether the expression levels of genes linked to the RAGE axis, including AGER (the gene encoding RAGE), Diaphanous 1 (DIAPH1), the cytoplasmic domain binding partner of RAGE that contributes to RAGE signaling, and GLO1 are differentially regulated by the degree of obesity and/or how these relate to inflammatory and adipocyte markers and their metabolic consequences. SUBJECTS/METHODS: We sought to answer this question by analyzing gene expression patterns of markers of the AGE/RAGE/DIAPH1 signaling axis in abdominal subcutaneous (SAT) and omental (OAT) adipose tissue from obese and morbidly obese subjects. RESULTS: In SAT, but not OAT, expression of AGER was significantly correlated with that of DIAPH1 (n = 16; [Formula: see text], [0.260, 1.177]; q = 0.008) and GLO1 (n = 16; [Formula: see text], [0.364, 1.182]; q = 0.004). Furthermore, in SAT, but not OAT, regression analyses revealed that the expression pattern of genes in the AGE/RAGE/DIAPH1 axis is strongly and positively associated with that of inflammatory and adipogenic markers. Remarkably, particularly in SAT, not OAT, the expression of AGER positively and significantly correlated with HOMA-IR (n = 14; [Formula: see text], [0.338, 1.249]; q = 0.018). CONCLUSIONS: These observations suggest associations of the AGE/RAGE/DIAPH1 axis in the immunometabolic pathophysiology of obesity and insulin resistance, driven, at least in part, through expression and activity of this axis in SAT.

Truncal pattern of subcutaneous fat distribution is associated with obesity and elevated blood pressure among children and adolescents.

BACKGROUND: The association between elevated blood pressure (BP) and childhood obesity has been documented in several studies. However, little is known the difference in BP levels among children and adolescents with different patterns of fat distribution. The present study examined the association of subcutaneous fat distributional pattern with obesity and elevated BP among children and adolescents. METHODS: A total of 38,687 students (19,386 boys and 19,301 girls) aged 7-17 years participated in the study. Body mass index (BMI) cutoff points recommended by the International Obesity Task Force (IOTF) were used to define overweight and general obesity. Abdominal obesity was defined as waist-to-height ratio (WHtR) ≥ 0.5. Relatively high BP (RHBP) status was defined as systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) ≥ 95th percentile for age and gender. All individuals were classified into four groups (Q1-Q4) according to the age and sex-specific quartiles of subscapular to triceps skinfold thickness ratio (STR), the prevalence rates of overweight, general obesity, abdominal obesity and RHBP among the four groups were compared. RESULTS: In both boys and girls, significant differences in the prevalence rates of overweight, general obesity, abdominal obesity and RHBP were observed among the four groups, an increasing trend was observed from the Q1 (STR <25 th) group to the Q4 (STR ≥ 75th) group (p < 0.01). Children and adolescents with high STR had higher prevalence of overweight, obesity and RHBP than their counterparts with low STR (p < 0.01). CONCLUSION: Truncal pattern of subcutaneous fat distribution is associated with obesity and elevated BP among children and adolescents. Public health attention should not only focus on the amount of body fat, but also on the distributional pattern of body fat.

Poland's syndrome: a concise review of the clinical features highlighting associated dermatologic manifestations.

Poland's syndrome is a rare congenital condition characterized by absence of the pectoralis major muscle and a wide spectrum of associated ipsilateral chest wall and upper extremity anomalies. Associated dermatologic anomalies classically include pectoral and axillary alopecia, anhidrosis due to the absence of sweat glands, and deficiency in subcutaneous fat. Functional limitations are minimal, and thus surgical correction is primarily indicated for aesthetic purposes. Chest wall reconstruction typically involves transposition of a latissimus dorsi myocutaneous flap with or without a temporary subcutaneous tissue expander prior to surgical reconstruction. Using the PubMed database, a literature review was done on Poland's syndrome. We summarize the key features of Poland's syndrome, including the epidemiology, clinical presentation, pathogenesis, and management, and highlight the dermatologic associations reported in the literature.

RF-antibioterapia con bajas dosis de penicilina en prevención secundaria de episodios de celulitis de extremidad inferior / Antibiotic Therapy With Low Doses of Penicillin for the Secondary Prevention of Recurrent Lower Extremity Cellulitis

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A cross-sectional survey of the association between bilateral topical prostaglandin analogue use and ocular adnexal features.

We studied the relation between prostaglandin analogue use and ocular adnexal features. We used a prospective, cross-sectional study involving 157 current, 15 past, and 171 never users of prostaglandin analogues. Patients 50 years of age or older and without conditions affecting ocular adnexal anatomy underwent glaucoma medication use history, external digital photography and systematic external adnexal exam. Two masked readers assessed the digital photos for upper lid dermatochalasis and lower lid steatoblepharon using a validated grading scheme. Another masked clinical examiner also assessed upper lid ptosis, levator muscle function, and inferior scleral show. We performed ordinal logistic regression analysis accounting for multiple covariates to assess the relation between prostaglandin analogue use and adnexal features. Multivariable analyses indicated there was a 230-fold increased risk of incremental involution of dermatochalasis (odds ratio (OR) = 2.30; 95% confidence interval (CI) 1.43-3.69; p = 5.44E-04) and a 249-fold increased risk of incremental loss of lower lid steatoblepharon (OR = 2.49; 95% CI, 1.54-4.03; p= 1.98E-04) associated with current prostaglandin analogue use (bimatoprost 0.03%, travoprost 0.005%, or latanoprost 0.004%) versus prostaglandin analogue never or past users. Upper lid ptosis (OR = 4.04; 95% CI, 2.43-6.72; p = 7.37E-08), levator dysfunction (OR = 7.51; 95% CI, 3.39-16.65; p = 6.74E-07) and lower lid retraction (OR = 2.60; 95% CI, 1.58-4.28; p = 1.72E-04) were highly associated with current prostaglandin analogue use versus prostaglandin analogue never or past users. The associations between prostaglandin analogue use and deepening of the upper lid sulci and between prostaglandin analogue use and loss of inferior periorbital fat are confirmed in this multivariable analysis. The associations between prostaglandin analogue use and levator muscle dysfunction and between prostaglandin analogue use and upper lid ptosis represent significant side effects that could impact visual function in glaucoma patients.

Vascular abnormalities correlate with decreased soft tissue volumes in idiopathic clubfoot.

BACKGROUND: Lower extremity vascular anomalies have been described for patients with clubfoot but few imaging studies have investigated effects on soft tissues such as fat and muscle. To make these assessments we need noninvasive, noncontrast agents to more safely image children. QUESTIONS/PURPOSES: We describe a novel noninvasive imaging protocol to identify vascular and soft tissue abnormalities in the lower limbs of patients with clubfoot and determine whether these abnormalities are present in patients who had recurrent clubfoot. PATIENTS AND METHODS: Three-dimensional noncontrast-enhanced MR angiography was used to identify vascular, bone, and soft tissue abnormalities in patients with clubfoot. We determined whether these abnormalities were more common in patients who had experienced recurrent clubfoot. RESULTS: Four patients with isolated unilateral clubfoot had arterial anomalies in the clubfoot limb. All patients had less muscle volume in the affected limb, and nine of 11 patients (82%) had less subcutaneous fat, with a mean difference of 0.56 cm(3) ± 0.36 cm(3) (range, 0.08-1.12 cm(3)). Vascular anomalies and decreased fat and muscle volumes were present in all three patients with recurrent clubfoot. CONCLUSIONS: We found a high frequency of vascular and soft tissue anomalies in the affected limbs of patients with unilateral clubfoot that may correlate with response to treatment.