A novel mutation of sgk-1 gene in central serous chorioretinopathy

AIM

To investigate the association of serum glucocorticoid kinase gene-1 (SGK-1) DNA variants with chronic central serous chorioretinopathy (CSC).

METHODS

We enrolled 32 eyes of 32 patients who were diagnosed with chronic CSC and composed 32 normal eyes as a control group. Peripheral blood was used for DNA extraction and polymerase chain reaction (PCR) amplification. SGK1 gene was sequenced by using BigDye^® Terminator v3.1 cycle sequencing KIT (Applied Biosystems, Foster City, CA, USA). The SGK1 gene and its variants were investigated in CSC patient group and control group.

RESULTS

We identified a new polymorphism M32V in two person in the patient group (Minor allele frequency (MAF)=0.009) on the region of 1-60 amino acids. The rs1057293 was located in the encoder region of the SGK 1 gene but not associated with CSC (P=0.68). An intrinsic rs1743966 is also not associated (P=0.28).

CONCLUSIONS

The new polymorphism M32V is located on the region of 1-60 amino acids which is necessary for localization to the mitochondria in CSC patient. This mutation is probably important for the energy metabolism and plays an important role in the cellular response to hyperosmotic stress and other stress stimuli. Both rs1057293 and rs1743966 are not associated with CSC.     

Molecular dynamics simulations provide molecular insights into the role of HLA‐B51 in Behçet's disease pathogenesis

Behçet's disease is an inflammatory disorder of unknown etiology. Genetic tendency has an important role in its pathogenesis, and HLA‐B51, a class I MHC antigen, has been recognized as the strongest susceptibility factor for Behçet's disease. Despite the confirmation of the association of HLA‐B51 with Behçet's disease in different populations, its pathogenic mechanisms remain elusive. HLA‐B51 differs in only two amino acids from HLA‐B52, other split antigen of HLA‐B5, which is not associated with Behçet's disease. These two amino acids are located in the B pocket of the antigen‐binding groove, which occupies the second amino acids of the bound peptides. To understand the nature of the HLA–peptide interactions, differences in structure and dynamics of two HLA alleles were investigated by molecular dynamics simulations using YAYDGKDYI, LPRSTVINI, and IPYQDLPHL peptides. For HLA‐B51, all bound peptides fluctuated to larger extent than HLA‐B52. Free energy profiles of unbinding process for YAYDGKDYI by steered molecular dynamics simulations showed that unbinding from HLA‐B52 results in greater free energy differences than HLA‐B51. These results suggest the possibility of an instability of HLA‐B51 associated with the repertoire of peptides, and this finding may provide significant insight to its pathogenic role in Behçet's disease.     

Extreme conformational diversity in human telomeric DNA

DNA with tandem repeats of guanines folds into G-quadruplexes made of a stack of G-quartets. In vitro, G-quadruplex formation inhibits telomere extension, and POT1 binding to the single-stranded telomeric DNA enhances telomerase activity by disrupting the G-quadruplex structure, highlighting the potential importance of the G-quadruplex structure in regulating telomere length in vivo. We have used single-molecule spectroscopy to probe the dynamics of human telomeric DNA. Three conformations were observed in potassium solution, one unfolded and two folded, and each conformation could be further divided into two species, long-lived and short-lived, based on lifetimes of minutes vs. seconds. Vesicle encapsulation studies suggest that the total of six states detected here is intrinsic to the DNA. Folding was severely hindered by replacing a single guanine, showing only the shortlived species. The long-lived folded states are dominant in physiologically relevant conditions and probably correspond to the parallel and antiparallel G-quadruplexes seen in high-resolution structural studies. Although rare under these conditions, the short-lived species determine the overall dynamics because they bridge the different long-lived species. We propose that these previously unobserved transient states represent the early and late intermediates toward the formation of stable G-quadruplexes. The major compaction occurs between the early and late intermediates, and it is possible that local rearrangements are sufficient in locking the late intermediates into the stably folded forms. The extremely diverse conformations of the human telomeric DNA may have mechanistic implications for the proteins and drugs that recognize G-rich sequences.     

Medial percutaneous hemi-epiphysiodesis improves the valgus tilt of the femoral head in developmental dysplasia of the hip (DDH) type-II avascular necrosis: Good outcome in 11 hips

Background and purpose

Avascular necrosis (AVN) is a major cause of disability after treatment of developmental dysplasia of the hip (DDH), leading to femoral head deformity, acetabular dysplasia, and osteoarthritis in adult life. Type-II AVN is characterized by retarded growth in the lateral aspect of the physis or by premature lateral fusion, which produces a valgus deformity of the head on the neck of the femur. We investigated the effect of medial percutaneous hemi-epiphysiodesis as a novel technique in the treatment of late-diagnosed type-II AVN.

Patients and methods

9 patients (11 hips) with a diagnosis of type-II AVN who underwent medial percutaneous hemi-epiphysiodesis after the surgical treatment for DDH were included in the study. 10 patients (12 hips) with the same diagnosis but who did not undergo hemi-epiphysodesis were chosen as a control group. Preoperative and postoperative articulotrochanteric distances, head-shaft angles, CE (center-edge) angles, and physeal inclination angles were measured. The treatment group underwent medial hemi-epiphysodesis at a mean age of 8 years. The mean ages of the treatment group and the control group at final follow-up were 14 and 12 years respectively. The mean duration of follow-up was 5.7 years in the treatment group and 8.3 years in the control group.

Results

Preoperative articulotrochanteric distance, head-shaft angle, and functional outcome at the final follow-up assessment were similar in the 2 groups. However, preoperative and postoperative CE angles and physeal inclination angles differed significantly in the treatment group (p < 0.05). The final epiphyseal valgus angles were better in the treatment group than in the control group (p = 0.05). The treatment group improved after the operation.

Interpretation

Medial percutaneous epiphysiodesis performed through a mini-incision under fluoroscopic control is a worthwhile modality in terms of changing the valgus tilt of the femoral head.Avascular necrosis (AVN) of the proximal femoral epiphysis is an iatrogenic complication of treatment for developmental dysplasia of the hip (DDH) (Danielsson 2000, Dhar 2003, Domalzki and Synder 2004, Roposch et al.2013). A late abnormality that may be the manifestation of the lateral portion of the capital femoral growth plate in type-II AVN alters the morphology of hip joint (Kalamchi and MacEwen 1980). When a progressive valgus deformity occurs in a patient with type-II AVN, problems associated with hip dysplasia may follow (Siffert 1981, Campbell and Tarlos 1990, Kim et al. 2000, Wu et al. 2010, Herring 2014). Due to inadequate coverage, reduced contact area between acetabulum and femoral head leads to early secondary osteoarthritis (Aronson 1986, Inoue et al. 2000, Herring 2014).The treatment decision for type-II AVN is challenging. Procedures such as varus femoral osteotomy and redirectional acetabular osteotomy have been used with a view to preventing future degenerative disease. However, these procedures are technically difficult and may result in serious complications (Siebenrock et al. 2013). On the other hand, as the main pathology is the growth disturbance at the lateral aspect of the femoral head, some form of arrest of the medial portion of the growth plate may be more logical in the treatment of type-II AVN (Herring 2014). We analyzed the radiographic and clinical outcomes of 11 hips in 9 patients with late-diagnosed type-II AVN who underwent percutaneous hemi-epiphysiodesis of the femoral head.     

Thrombus aspiration during primary percutaneous coronary intervention associated with reduced platelet activation

Objectives:

To determine the effect of thrombectomy on platelet function in patients undergoing primary percutaneous coronary intervention (PPCI) for ST segment elevation myocardial infarction (STEMI).

Methods:

This retrospective study included 413 consecutive STEMI patients who underwent PPCI between March 2012 and September 2013 at Kartal Kosuyolu High Specialty Education and Research Hospital, Istanbul, Turkey that were assigned to the thrombus aspiration (TA) group or the non-TA group. Platelet count and mean platelet volume (MPV) were obtained at baseline and 24 hours (h), 48 h, and 72 h post PPCI.

Results:

Baseline MPV was similar in both groups, whereas the baseline platelet count was higher in the TA group (p=0.42 and p=0.002). The platelet count was higher in the TA group 24 h post PPCI (p=0.02), but was similar in both groups 48 h and 72 h post PPCI (p=0.18 and p=0.07). The MPV 48 h and 72 h post PPCI was higher in the non-TA group than in the TA group (8.4 ± 1.3 fL versus 8.7 ± 1.6 fL [p=0.04] and 8.5 ± 1.1 fL versus 8.9 ± 1.5 fL [p=0.04]).

Conclusion:

Thrombectomy reduced platelet activity via removal of thrombi from the coronary arteries in patients undergoing PPCI for STEMI.In acute ST-segment elevation myocardial infarction (STEMI), the main initiating factor is atherosclerotic plaque rupture or erosion, then platelets become activated and aggregated leading to acute coronary artery occlusion.1 Primary percutaneous coronary intervention (PPCI) is the standard treatment in patients with STEMI.2 In recent years, implementation of adjunctive mechanical and pharmacological therapies during PPCI, including manual thrombus aspiration (TA), has improved myocardial reperfusion and clinical outcome in STEMI patients.3-5 In daily practice, thrombectomy devices are used to remove thrombi or to prevent embolization of thrombi and plaque during PPCI.6 Platelet volume is a marker of platelet activation and is measured via mean platelet volume (MPV).7 An increase in MPV can occur in cases of acute myocardial ischemia, acute myocardial infarction, coronary atherosclerosis,8,9 and early stent thrombosis (ST).10 The Percutaneous Coronary Intervention in Acute Myocardial Infarction (TAPAS) study5 showed that TA therapy during PPCI decreases mortality and reinfarction rate.5 We speculate that the good results obtained with TA therapy are not only related to improved tissue perfusion but also may be related to reduced platelet activation. Therefore, the present study aimed to determine the effect of thrombectomy on platelet function and ST in patients undergoing PPCI for STEMI.     

Body position and obstructive sleep apnea syndrome

In adults, influence of body position on the occurrence of respiratory events during sleep is recognized, and increased numbers of respiratory events occur when the supine position is assumed.1-4 In 1985, Orr et al. showed that body position did not influence respiratory events during sleep in children.5 Recently, Fernandes do Prado et al. showed that children had a lower obstructive apnea hypopnea index (AHI) in supine position.6 Results of these two studies are different from others performed on adults. Moreover, upper airway abnormalities were not considered in these studies.The aim of the present study was to evaluate the effect of body position on obstructive respiratory events in children with different upper airway findings.