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.     

Case of a palatal tic resembling palatal tremor in a patient with Tourette syndrome.

We describe a case of a palatal tic resembling palatal tremor (PT) in a young female patient with a previously unrecognized mild Tourette syndrome. At the time of her visit, the patient complained about ear clicks that were audible to others. We discuss the differential diagnoses of hyperkinetic palatal movements emphasizing the ongoing discussion about essential PT representing a more heterogeneous disorder than previously thought.     

166Ho-DOTMP radiation-absorbed dose estimation for skeletal targeted radiotherapy.

166Ho-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonate (DOTMP) is a tetraphosphonate molecule radiolabeled with 166Ho that localizes to bone surfaces. This study evaluated pharmacokinetics and radiation-absorbed dose to all organs from this beta-emitting radiopharmaceutical. METHODS: After two 1.1-GBq administrations of 166Ho-DOTMP, data from whole-body counting using a gamma-camera or uptake probe were assessed for reproducibility of whole-body retention in 12 patients with multiple myeloma. The radiation-absorbed dose to normal organs was estimated using MIRD methodology, applying residence times and S values for 166Ho. Marrow dose was estimated from measured activity retained after 18 h. The activity to deliver a therapeutic dose of 25 Gy to the marrow was determined. Methods based on region-of-interest (ROI) and whole-body clearance were evaluated to estimate kidney activity, because the radiotracer is rapidly excreted in the urine. The dose to the surface of the bladder wall was estimated using a dynamic bladder model. RESULTS: In clinical practice, gamma-camera methods were more reliable than uptake probe-based methods for whole-body counting. The intrapatient variability of dose calculations was less than 10% between the 2 tracer studies. Skeletal uptake of 166Ho-DOTMP varied from 19% to 39% (mean, 28%). The activity of 166Ho prescribed for therapy ranged from 38 to 67 GBq (1,030-1,810 mCi). After high-dose therapy, the estimates of absorbed dose to the kidney varied from 1.6 to 4 Gy using the whole-body clearance-based method and from 8.3 to 17.3 Gy using the ROI-based method. Bladder dose ranged from 10 to 20 Gy, bone surface dose ranged from 39 to 57 Gy, and doses to other organs were less than 2 Gy for all patients. Repetitive administration had no impact on tracer biodistribution, pharmacokinetics, or organ dose. CONCLUSION: Pharmacokinetics analysis validated gamma-camera whole-body counting of 166Ho as an appropriate approach to assess clearance and to estimate radiation-absorbed dose to normal organs except the kidneys. Quantitative gamma-camera imaging is difficult and requires scatter subtraction because of the multiple energy emissions of 166Ho. Kidney dose estimates were approximately 5-fold higher when the ROI-based method was used rather than the clearance-based model, and neither appeared reliable. In future clinical trials with 166Ho-DOTMP, we recommend that dose estimation based on the methods described here be used for all organs except the kidneys. Assumptions for the kidney dose require further evaluation.     

Antibacterial properties of 4 orthodontic cements.

BACKGROUND: White spot lesions are observed in nearly 50% of patients undergoing orthodontic treatment. Long-lasting antibacterial properties of orthodontic cements can reduce this phenomenon. METHODS: The antibacterial properties of 4 orthodontic cements were evaluated by direct contact test (DCT) and agar diffusion test (ADT). With the DCT technique, octet specimens of glass ionomer (CX-Plus; Shofu, Kyoto, Japan), reinforced glass ionomer (GC Fuji ORTHO LC; GC Corporation, Tokyo, Japan), and 2 composite (Transbond XT and Transbond Plus; 3M Unitek, Monrovia, Calif) orthodontic cements were placed on the sidewalls of wells of a 96-microtiter plate. Streptococcus mutans cells (ca. 1 x 10(6) ) were placed on the surface of each specimen for 1 hour at 37 degrees C. Then, fresh media was added to each well, and bacterial growth was monitored for 16 hours with a temperature-controlled spectrophotometer. This was repeated on specimens aged in phosphate-buffered saline for 1 day, 1 week, and 1 month. The ADT was performed by placing specimens in wells punched in agar plates. RESULTS: Measurement of the halo in bacterial lawn after 48 hours showed that only the glass ionomer cement (CX-Plus) produced an inhibition zone (1.2 mm around the sample). Results at the DCT showed that only the reinforced glass ionomer cement (GC Fuji ORTHO LC) exhibited potent antibacterial activity, which lasted 1 week and diminished over the next 3 weeks. CONCLUSIONS: The reinforced glass ionomer cement possessed the most potent and long-lasting antibacterial activity.     

Is varicocelectomy indicated in subfertile men with clinical varicoceles who have asthenospermia or teratospermia and normal sperm density?

OBJECTIVE: Varicocele is the most common treatable cause of male infertility and is associated with progressive decline in testicular function. Varicocelectomy, a commonly performed operation, is indicated in infertile males with varicoceles who have oligospermia, asthenospermia, teratospermia or a combination of these factors. It is not clear if varicocelectomy is indicated if the patients have normal sperm density associated with asthenospermia or teratospermia. METHODS: We reviewed 167 patients with varicocele-associated male infertility over a 7-year period (December 1999-November 2005). Pre- and post-varicocelectomy seminal fluid analyses, assessed using the World Health Organization criteria, were obtained at intervals of 4-6 months. Wilcoxon signed rank tests were used to evaluate for statistical significance and P < or = 0.05 was considered significant. RESULTS: The mean age of the patients and their spouses were 35 and 28 years, respectively. The mean duration of infertility was 3.2 years (range, 1.5-7.5). Oligospermia, teratospermia, asthenospermia, oligospermia, asthenospermia and teratospermia (OAT) syndrome and azoospermia were found preoperatively in 106 (63.5%), 58 (34.7%), 154 (92%), 118 (71%) and 15 (9%) patients, respectively. Overall, significant improvements in semen volume (P < 0.001), sperm density (P < 0.001), sperm motility (P < 0.001) and sperm vitality (P < 0.001) were obtained after varicocelectomy. There was, however, no significant improvement in sperm morphology after varicocelectomy (P = 0.220). When patients with preoperative oligospermia (sperm density, <20 million/mL) were considered separately, varicocelectomy led to significant improvement in all the semen parameters except the sperm morphology (P = 0.183). Conversely, when varicocele patients with a sperm density of > or =20 million/mL (normospermia) associated with asthenospermia and/or teratospermia were considered separately, they did not show significant improvement in any of the semen parameters after varicocelectomy (P > 0.05). In addition, azoospermic patients did not show significant improvement in any of the semen parameters (P > 0.05) CONCLUSION: No significant improvement in semen parameters may be obtained in patients with clinical varicocele and preoperative normospermia. It is possible that only patients with preoperative oligospermia may benefit from varicocelectomy. Larger multi-institutional studies are needed to determine more definitively if asthenospermia or teratospermia in normospermic subfertile males with clinical varicoceles are in fact indications for varicocelectomy.