A genome wide association study identifies new genes potentially associated with eyelid sagging

Sagging eyelid is considered as an outward of skin ageing and may cause medical issues. However, little is known about the factors involved in sagging eyelid. The study, which aims at determining genetic risk factors for eyelid sagging, was conducted in a cohort of 502 unrelated Caucasian women living in the Paris region. All included participants were aged between 44 and 70 years old (mean age, 57.6 years old). The severity of sagging eyelid was graded in 6 categories by a dermatologist using standardized photographs of the face. A genome wide association study adjusted on potential risk factors (including age and smoking habits) was conducted to identify genetic associations. Two single nucleotide polymorphisms in total linkage disequilibrium on chromosome 10, rs16927253 (P = 7.07 × 10^‐10) and rs4746957 (P = 1.06 × 10^‐8), were significantly associated with eyelid sagging severity. The rs16927253‐T and rs4746957‐A alleles showed a dominant protective effect towards eyelid sagging. These polymorphisms are located in intronic parts of the H2AFY2 gene which encodes a member of the H2A histone family and very close to the AIFM2 gene that induces apoptosis. Additionally, single nucleotide polymorphisms with a false discovery rate below 0.25 were located nearby the type XIII collagen COL13A1 gene on chromosome 10 and in the ADAMTS18 gene on chromosome 16. Several relevant genes were identified by the genome wide association study for their potential role in the sagging eyelid severity.     

Assessment methods for the evaluation of vitiligo

There is no standardized method for assessing vitiligo. In this article, we review the literature from 1981 to 2011 on different vitiligo assessment methods. We aim to classify the techniques available for vitiligo assessment as subjective, semi‐objective or objective; microscopic or macroscopic; and as based on morphometry or colorimetry. Macroscopic morphological measurements include visual assessment, photography in natural or ultraviolet light, photography with computerized image analysis and tristimulus colorimetry or spectrophotometry. Non‐invasive micromorphological methods include confocal laser microscopy (CLM). Subjective methods include clinical evaluation by a dermatologist and a vitiligo disease activity score. Semi‐objective methods include the Vitiligo Area Scoring Index (VASI) and point‐counting methods. Objective methods include software‐based image analysis, tristimulus colorimetry, spectrophotometry and CLM. Morphometry is the measurement of the vitiliginous surface area, whereas colorimetry quantitatively analyses skin colour changes caused by erythema or pigment. Most methods involve morphometry, except for the chromameter method, which assesses colorimetry. Some image analysis software programs can assess both morphometry and colorimetry. The details of these programs (Corel Draw, Image Pro Plus, AutoCad and Photoshop) are discussed in the review. Reflectance confocal microscopy provides real‐time images and has great potential for the non‐invasive assessment of pigmentary lesions. In conclusion, there is no single best method for assessing vitiligo. This review revealed that VASI, the rule of nine and Wood’s lamp are likely to be the best techniques available for assessing the degree of pigmentary lesions and measuring the extent and progression of vitiligo in the clinic and in clinical trials.     

Geomechanical behavior of the reservoir and caprock system at the In Salah CO2 storage project

Almost 4 million metric tons of CO₂ were injected at the In Salah CO₂ storage site between 2004 and 2011. Storage integrity at the site is provided by a 950-m-thick caprock that sits above the injection interval. This caprock consists of a number of low-permeability units that work together to limit vertical fluid migration. These are grouped into main caprock units, providing the primary seal, and lower caprock units, providing an additional buffer and some secondary storage capacity. Monitoring observations at the site indirectly suggest that pressure, and probably CO₂, have migrated upward into the lower portion of the caprock. Although there are no indications that the overall storage integrity has been compromised, these observations raise interesting questions about the geomechanical behavior of the system. Several hypotheses have been put forward to explain the measured pressure, seismic, and surface deformation behavior. These include fault leakage, flow through preexisting fractures, and the possibility that injection pressures induced hydraulic fractures. This work evaluates these hypotheses in light of the available data. We suggest that the simplest and most likely explanation for the observations is that a portion of the lower caprock was hydrofractured, although interaction with preexisting fractures may have played a significant role. There are no indications, however, that the overall storage complex has been compromised, and several independent data sets demonstrate that CO₂ is contained in the confinement zone.In Salah is an industrial-scale carbon capture and storage project located in central Algeria. Between 2004 and 2011, 3.8 million metric tons of CO₂ were injected into an anticlinal structure at ∼1,800 m depth. Storage integrity at the site is provided by a massive, 950-m-thick caprock that sits above the injection interval (Fig. 1). It consists of a number of low-permeability units that work together to limit vertical fluid migration. These are grouped into main caprock units, providing the primary seal, and lower caprock units, providing an additional buffer and some secondary storage capacity.Open in a separate windowFig. 1.Stratigraphic column with interval depths at well KB-502. Depth is given as meters of true vertical depth below the rotary table (m TVD brt) of the drilling rig, a common elevation datum in the oil and gas industry.In June 2011, injection operations halted at the site to allow reevaluation of the injection strategy (1). At the time, several monitoring observations suggested that pressure, and probably CO₂, had migrated vertically into the lower portion of the caprock. Although there are no indications that overall storage integrity has been compromised, these observations raise interesting questions about the geomechanical behavior of the reservoir and lower caprock system.Several hypotheses have been put forward by various groups to explain these observations. These include fault leakage, flow through preexisting fractures, or the possibility that injection pressures hydraulically fractured a portion of the lower seal (2–13). In this work, we evaluate these hypotheses in light of the available data. We suggest that the most likely explanation for the observed behavior is that the lower caprock was hydrofractured, although interaction with preexisting fractures may have played a significant role. Previous studies by Bissell and colleagues (4) and Oye and colleagues (8) have shown that injectivity and microseismic data show indications of fracturing behavior, at least in the reservoir and possibly in the overburden. Here, we use well data to constrain the state of stress in the reservoir and lower caprock, providing strong support for the hydrofracture hypothesis.This work also highlights those monitoring and analysis methods that have been most useful for understanding the field behavior, as well as lessons learned and potential improvements. This perspective can guide future carbon storage projects.     

High-fat diet induced an oxidative stress in white adipose tissue and disturbed plasma transition metals in rat: prevention by grape seed and skin extract

Obesity is a public health problem characterized by increased accumulation of fat into adipose tissues leading to oxidative stress, dyslipidemia, and chronic inflammatory status. We used an experimental model of high-fat diet-induced obesity to analyze the link between dyslipidemia, oxidative stress, and fat accumulation into adipose tissue of rats, as well as the involvement of intracellular mediators such as transition metals on signal transduction. We also looked at the ability of a grape seed and skin extract (GSSE) from a Tunisian cultivar to prevent fat-induced disturbances. Data showed that a high-fat diet (HFD) provoked dyslipidemia into plasma which is linked to an oxidative stress, an accumulation of transition metals such as manganese, copper, and zinc and a depletion of iron. GSSE prevented dyslipidemia by modulating lipase activity, together with increased antioxidant capacity and depletion of transition metals as well as of free radicals such as O₂ ^? and OH. These data indicated that GSSE has important preventive effects on HFD-induced obesity and oxidative stress whose transduction seems to involve transition metals. GSSE should be used as a safe anti-obesity agent that could find potential applications in metabolic disorders involving transition metals dyshomeostasis.     

Medical treatment for sphincter of oddi dysfunction:Can it replace endoscopic sphincterotomy?

AIM:To report the results of a medical management of sphincter of oddi dysfunction(SOD) after an intermediate follow-up period.METHODS:A total of 59 patients with SOD(2 men and 57 women,mean age 51 years old) were included in this prospective study.After medical treatment for one year,the patients were clinically re-evaluated after an average period of 30 mo.RESULTS:The distribution of the patients according to the Milwaukee's classification was the following:11 patients were type 1,34 were type 2 and 14 were type 3.Fourteen patients underwent an endoscopic sphincterotomy(ES) after one year of medical treatment.The median intermediate follow-up period was 29.8 ± 3 mo(3-72 mo).The initial effectiveness of the medical treatment was complete,partial and poor among 50.8%,13.5% and 35%,respectively,of the patients.At the end of the follow-up period,37 patients(62.7%) showed more than 50% improvement.The rate of improvement in patients who required ES was not significantly different compared with the patients treated conservatively(64.2% vs 62.2%,respectively).CONCLUSION:Our study confirms that conservative medical treatment could be an alternative to endoscopic sphincterotomy because,after an intermediate follow-up period,the two treatments show the same success rates.     

3‐Keto‐1,5‐bisphosphonates Alleviate Serum‐Oxidative Stress in the High‐fat Diet Induced Obesity in Rats

Obesity has become a leading global health problem owing to its strong association with a high incidence of oxidative stress. Many epidemiologic studies showed that an antioxidant supplementation decreases the state of oxidative stress. In the present work, a HFD ‐induced rat obesity and oxidative stress were used to investigate the link between fat deposition and serum‐oxidative stress markers. We also studied the effect of a chronic administration of 3‐keto‐1,5‐bisphosphonates 1 (a & b) (40 μg/kg/8 weeks/i.p.). Exposure of rats to HFD during 16 weeks induced fat deposition, weight gain and metabolic disruption characterized by an increase in cholesterol, triglyceride and glycemia levels, and a decrease in ionizable calcium and free iron concentrations. HFD also induced serum‐oxidative stress status vocalized by an increase in ROS ( H ₂ O ₂ ), MDA and PC levels, with a decrease in antioxidant enzyme activity ( CAT , GP x , SOD ). Importantly, 3‐keto‐1,5‐bisphosphonates corrected all the deleterious effects of HFD treatment in vivo, but it failed to inhibit lipases in vitro and in vivo. These studies suggest that 3‐keto‐1,5‐bisphosphonates 1 could be considered as safe antioxidant agents that should also find other potential biological applications.     

The Influence of Media Coverage and Governmental Policies on Google Queries Related to COVID-19 Cutaneous Symptoms: Infodemiology Study

BackgroundDuring COVID-19, studies have reported the appearance of internet searches for disease symptoms before their validation by the World Health Organization. This suggested that monitoring of these searches with tools including Google Trends may help monitor the pandemic itself. In Europe and North America, dermatologists reported an unexpected outbreak of cutaneous acral lesions (eg, chilblain-like lesions) in April 2020. However, external factors such as public communications may also hinder the use of Google Trends as an infodemiology tool.ObjectiveThe study aimed to assess the impact of media announcements and lockdown enforcement on internet searches related to cutaneous acral lesions during the COVID-19 outbreak in 2020.MethodsTwo searches on Google Trends, including daily relative search volumes for (1) “toe” or “chilblains” and (2) “coronavirus,” were performed from January 1 to May 16, 2020, with the United States, the United Kingdom, France, Italy, Spain, and Germany as the countries of choice. The ratio of interest over time in “chilblains” and “coronavirus” was plotted. To assess the impact of lockdown enforcement and media coverage on these internet searches, we performed an interrupted time-series analysis for each country.ResultsThe ratio of interest over time in “chilblains” to “coronavirus” showed a constant upward trend. In France, Italy, and the United Kingdom, lockdown enforcement was associated with a significant slope change for “chilblain” searches with a variation coefficient of 1.06 (SE 0.42) (P=0.01), 1.04 (SE 0.28) (P<.01), and 1.21 (SE 0.44) (P=0.01), respectively. After media announcements, these ratios significantly increased in France, Spain, Italy, and the United States with variation coefficients of 18.95 (SE 5.77) (P=.001), 31.31 (SE 6.31) (P<.001), 14.57 (SE 6.33) (P=.02), and 11.24 (SE 4.93) (P=.02), respectively, followed by a significant downward trend in France (–1.82 [SE 0.45]), Spain (–1.10 [SE 0.38]), and Italy (–0.93 [SE 0.33]) (P<.001, P=0.004, and P<.001, respectively). The adjusted R² values were 0.311, 0.351, 0.325, and 0.305 for France, Spain, Italy, and the United States, respectively, suggesting an average correlation between time and the search volume; however, this correlation was weak for Germany and the United Kingdom.ConclusionsTo date, the association between chilblain-like lesions and COVID-19 remains controversial; however, our results indicate that Google queries of “chilblain” were highly influenced by media coverage and government policies, indicating that caution should be exercised when using Google Trends as a monitoring tool for emerging diseases.     

Infantile haemangioma: Part I. Pathophysiology,epidemiology, clinical features,life cycle and associated structural abnormalities

Infantile haemangioma (IH) is the most common tumour of infancy. Its typical natural history is characterized by an early rapid growth following birth and a slow spontaneous regression phase within a period of 3 to 7 years. The exact aetiopathogeny underlying IH is still to be fully understood, but the role of fetal hypoxic stress is strongly suggested as a triggering signal in epidemiological studies. IH are composed of a complex mixture of cells including multipotent stem cells, a majority of immature endothelial cells, pericytes, dendritic cells and in the late stage, adipocytes. Most of IH are nodular and are not associated with malformations. However, in some cases, IH referred to as segmental may be associated with developmental abnormalities such as PHACES and PELVIS/SACRAL syndromes.