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.     

Oxazole,pyrazole and piperidine derivatives having an o-hydroxyaryl moiety with anticipated molluscicidal activity

The condensation reactions of hippuric acid and its furyl derivative with salicylaldehydes or that of salicylhippuric acid analogues with furaldehyde led to the corresponding oxazoles. These were subsequently treated with hydrazine hydrate, hydroxylamine or subjected to alkaline hydrolysis to yield new o-hydroxyaryl or salicyl containing derivatives. 5-Substituted salicylanilides were treated with piperidine and formaldehyde in a Mannich type reaction affording the corresponding 3-(N-piperidinomethyl) salicylanilides. It was noticed that the presence of an electron donating group in position 3 in the salicylanilide moiety decreases the molluscicidal activity.     

Endothelial modulation of vasoconstrictor responses to endothelin-1 in human placental stem villi small arteries.

1. The aim of this study was to assess the role of endothelial cells in the modulation of vasocontractile responses to endothelin-1 (ET-1) of human placental vasculature. 2. Isolated stem villi small arteries (diameter = 170-250 microns) were obtained from healthy parturients who underwent caesarean surgery during the 39th week of pregnancy for cephalo-pelvic disproportion. Isometric tension was measured in vascular rings mounted in a myograph system and challenged with ET-1 (10(-12) to 10(-6) M). 3. The vasocontractile response to ET-1 was significantly (P < 0.001) increased in endothelial-denuded (active tension = 1156 +/- 214 mN mm-1) as compared with endothelial-preserved vascular rings (active tension = 458 +/- 48 mN mm-1). This difference was significantly (P < 0.05) but only partly abolished by the NO synthase inhibitor N omega-nitro-L-arginine (L-NOARG, 10(-4) M). 4. In endothelial-preserved rings submaximally precontracted with 5-hydroxytryptamine (10(-6) M), ET-1 (10(-12) to 10(-9) M) induced dose-dependent relaxation (maximum relaxation = 70 +/- 7%) at 10(-9) M, which was followed, at higher doses (10(-8) to 10(-6) M), by a contraction. In contrast, no relaxation was seen in endothelial-denuded rings. The relaxation in rings with endothelium was significantly (P < 0.001) reduced by L-NOARG (10(-4) M. Moreover, it was totally abolished by combined pretreatment with L-NOARG (10(-4) M) and the sulphonylurea glibenclamide (10(-5) M).(ABSTRACT TRUNCATED AT 250 WORDS)     

Kenny–Caffey syndrome: an Arab variant?

We describe 2 unrelated Bedouin girls who met the criteria for the diagnosis of Kenny-Caffey syndrome. The girls had some unusual features--microcephaly and psychomotor retardation--that distinguish the Kenny-Caffey syndrome profile in Arab children from the classical Kenny-Caffey syndrome phenotype characterized by macrocephaly and normal intelligence. The 2 girls did not harbor the 22q11 microdeletion (the hallmark of the DiGeorge cluster of diseases) that we previously reported in another Bedouin family with the Kenny-Caffey syndrome (Sabry et al. J Med Genet 1998: 35(1): 31-36). This indicates considerable genetic heterogeneity for this syndrome. We also review previously reported 44 Arab/Bedouin patients with the same profile of hypoparathyroidism, short stature, seizures, mental retardation and microcephaly. Our results suggest that these patients represent an Arab variant of Kenny-Caffey syndrome with characteristic microcephaly and psychomotor retardation. We suggest that all patients with Kenny-Caffey syndrome should be investigated for the 22q11 microdeletion. Other possible genetic causes for the Kenny-Caffey syndrome or its Arab variant include chromosome 10p abnormalities.     

Lessons not learned from the generalist initiatives.

The grouping of the primary care specialties (general internal medicine, general pediatrics, and family medicine) for research purposes is at best limiting the value of the information that is found and, at worst, leading researchers to erroneous conclusions. For example, three large studies each showed differences in abilities to predict students' specialty choices in primary care (e.g., in one study, the investigators correctly predicted 3% of those choosing general internal medicine, 29% considering general pediatrics, and 51% considering family medicine). These and related findings suggest that medical students entering the three primary care specialties are not a homogeneous group. While there were some factors predictive for all primary care specialties, there were more factors that were unique to the individual specialties Grouping the specialties may not reveal factors that are significantly related to only one of the specialties. In addition, when a variable operates in different ways for different specialties, findings where the specialties are combined can show a reduced effect of that variable or even no effect, because the directions of effects cancel each other. Researchers can fruitfully examine the primary care specialties as a group but at the same time report their data for the individual specialties, which would greatly increase our knowledge both of primary care and also about the similarities and dissimilarities of its component specialties. However, the best models continue to be either research in which the sample size is large enough to compare specialty groups statistically or research with a focus on just one of the primary care specialties.     

Internal architecture of the talus: implication for talar fracture

The internal architecture of the talus has not previously been well described even though the morphological anatomy and the blood supply have been studied extensively. This study describes the internal architecture of the talus regarding its trabecular orientation, using high-resolution x-ray images of 13 dry tali and thick sections in the coronal, sagittal, and axial planes. The trabecular arrays and their relationship to talar fractures are described. The trabecular content of the neck of the talus is less than that of the head or the body. The direction of the trabecula in the neck is different from the orientation of the talar body trabeculae.     

Evaluation of crude and purified Toxocara canis antigens in serodiagnosis of human toxocariasis

Three serological tests: Immunodiffusion (ID), Counterimmunoelectrophoresis (CIEP) and Enzyme-linked immunosorbent assay (ELISA) were used to study the role of crude adult worm antigen (CAWA) of Toxocara canis and each of its purified fractions in the serodiagnosis of human toxocariasis. Sensitivities of the three tests were lower in the ocular than in the visceral group, using different antigens. Purified fraction 1 showed more sensitive and specific reactions in the three tests, compared to CAWA or purified fraction 2 (P-F2) antigen. The other purified fractions (P-F3, P-F4 and P-F5) gave no positive reactions in any of the three tests. Using P-F1 antigen, ELISA was the most sensitive technique for diagnosis of both visceral and ocular toxocariasis followed by CIEP and then ID and the difference was statistically significant. However, CIEP was the most specific test followed by ELISA and lastly ID test. The ELISA test using Excretory-Secretory (E-S) larval antigen of Toxocara canis was less sensitive than the ELISA test using P-F1, although it was 100% specific. Thus, ELISA test using P-F1 is the test of choice for diagnosis of human toxocariasis, but when the specificity of a reaction is in doubt, CIEP test using the same antigen can be of value.     

Calcaneus fractures with subluxation of the posterior facet. A surgical indication

The charts and radiographs of 118 patients with 126 intraarticular fractures of the calcaneus were reviewed retrospectively. Eleven of 126 (8.7%) calcaneal fractures had injuries consisting of intraarticular calcaneal fracture, lateral subluxation or dislocation of the posterior facet, fracture extension into the calcaneocuboid joint, peroneal tendon subluxation, subluxation of the talus in the ankle mortise, and complete disruption of the anterior talofibular and calcaneal fibular ligaments or fracture of the lateral malleolus. There were six women and five men. The average age was 40 years (range, 17-65 years). The mechanism of injury was a motor vehicle accident in eight and a fall from a height in three. According to the classification of Sanders et al eight fractures were Type II, one was Type III, and two were Type IV. Followup at an average of 26 months (range, 14-38 months) showed that eight of 11 patients (72.7%) had either good or excellent results. When lateral subluxation of the posterior facet of the calcaneus is identified with a preoperative computed tomography scan, operative management is indicated, and the surgeon should search for associated injuries that should be addressed at the time of surgery.