Relationship of Plasminogen Activator Inhibitor 1 4G/5G Gene Polymorphism and Nontraumatic Lunatum Avascular Necrosis.

PURPOSE: Plasminogen activator inhibitor 1 (PAI-1) is a critical enzyme that regulates coagulation and fibrinolytic systems. The aim of this study was to determine the role of PAI-1 4G/5G polymorphism in nontraumatic avascular necrosis of the lunate. METHODS: The study included 45 patients with Kienböck disease and 45 healthy individuals as a control group. In both groups, genomic DNA was extracted from peripheral blood samples to determine the distributions of PAI-1 4G/5G polymorphism using allele-specific polymerase chain reaction and sequencing. RESULTS: No statistically significant difference was determined in the distribution of the gene polymorphism between the patient and control groups. We found the 5G/5G genotype to be 1.7 times higher in the control group compared with the patient group. A 1.6-fold increase in the 4G homozygote genotype was identified in the patient group. The patient and control groups were also evaluated for 4G/4G plus 4G/5G and 5G/5G in terms of genotype distribution. No statistically significant difference was found. CONCLUSIONS: The findings suggest that the PAI-1 4G/4G polymorphism is not a genetic risk for Kienböck disease. CLINICAL RELEVANCE: This study aimed to reveal the genetic etiology of Kienböck disease.

Exome-sequencing in a large population-based study reveals a rare Asn396Ser variant in the LIPG gene associated with depressive symptoms.

Despite a substantial genetic component, efforts to identify common genetic variation underlying depression have largely been unsuccessful. In the current study we aimed to identify rare genetic variants that might have large effects on depression in the general population. Using high-coverage exome-sequencing, we studied the exonic variants in 1265 individuals from the Rotterdam study (RS), who were assessed for depressive symptoms. We identified a missense Asn396Ser mutation (rs77960347) in the endothelial lipase (LIPG) gene, occurring with an allele frequency of 1% in the general population, which was significantly associated with depressive symptoms (P-value=5.2 × 10-08, ß=7.2). Replication in three independent data sets (N=3612) confirmed the association of Asn396Ser (P-value=7.1 × 10-03, ß=2.55) with depressive symptoms. LIPG is predicted to have enzymatic function in steroid biosynthesis, cholesterol biosynthesis and thyroid hormone metabolic processes. The Asn396Ser variant is predicted to have a damaging effect on the function of LIPG. Within the discovery population, carriers also showed an increased burden of white matter lesions (P-value=3.3 × 10-02) and a higher risk of Alzheimer's disease (odds ratio=2.01; P-value=2.8 × 10-02) compared with the non-carriers. Together, these findings implicate the Asn396Ser variant of LIPG in the pathogenesis of depressive symptoms in the general population.

Isolation and identification of Treponema pedis and Treponema phagedenis-like organisms from bovine digital dermatitis lesions found in dairy cattle in Turkey.

The isolation and identification of microorganisms associated with digital dermatitis (DD) in Turkish dairy cattle was investigated using punch skin biopsy samples from typical clinical lesions; they were collected from dairy farms and abattoirs in 5 different geographical locations in Turkey. Morphological characteristics and flagellation types were examined using a transmission electron microscope, and their enzyme profiles by enzyme activation kits; their catalase reaction characteristics were evaluated by the addition of 3% H2O2. Their phylogenies were identified using 16S rRNA and the results compared with known gene bank data. Bacterial cells were 5.0 to 18.2 µm long, 0.2 to 0.5 µm wide, and their minimum number of periplasmic flagellum was 4 (4:8:4) with a maximum of 8 (8:16:8). All isolates were catalase negative. Of the spirochetes isolated and identified, group I organisms showed close similarity with Treponema pedis (99% genetic homology), whereas those in group II were similar to Treponema phagedenis (98% homology). This is the first report of specific sub-groups of Treponema spp., isolated from Turkish dairy cattle presenting with DD lesions, being associated with this disease; these morphotypes were similar to those found globally in housed dairy cattle units and are probably significant microorganisms associated with the aetiopathogensis of this infectious disease causing acute bovine lameness. These results suggest that the distribution of DD-associated treponemes is not specific to particular geographic regions of Turkey.

Somatic, positive and negative domains of the Center for Epidemiological Studies Depression (CES-D) scale: a meta-analysis of genome-wide association studies.

BACKGROUND: Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains. METHOD: We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons). RESULTS: One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (p discovery = 3.82 × 10-8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (p discovery+replication = 1.10 × 10-6) with evidence of heterogeneity. CONCLUSIONS: Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.

Subgross and macroscopic investigation of the coeliac artery in the chinchilla (chinchilla lanigera).

The knowledge of branching and variations of the coeliac artery is clinically important, especially in the surgical operations and non-surgical treatments.Moreover, the chinchillas abdominal region have been used as a model in some surgical experimental researches. In this frame, we have aimed to explain the branching of this artery in the chinchillas detailedly. A total of 10 adult, healthy,male chinchillas (chinchilla lanigera) were used to investigate the origin and the course of the coeliac artery and its branches. Coloured latex was injected into the carotid arteries, following conventional anatomical applications. The results indicated that the coeliac artery was divided into 4 branches such as left gastricartery, hepatic artery, splenic artery and gastrolienal artery. The left gastric artery was a continuity of the coeliac artery and the main vessel of the stomach. The hepatic artery was divided into the left lateral branch, the left medial branch and the right branch. The splenic artery was covered by the pancreas tissue and sent branches to the pancreas. The gastrolienal artery was supplying the fundus of the stomach and the dorsal extremity of the spleen. We believe that the findings will be of help to the researchers interested in the anatomical area, surgeons and experimental researches.

Genetic risk profiles for depression and anxiety in adult and elderly cohorts.

The first generation of genome-wide association studies (GWA studies) for psychiatric disorders has led to new insights regarding the genetic architecture of these disorders. We now start to realize that a larger number of genes, each with a small contribution, are likely to explain the heritability of psychiatric diseases. The contribution of a large number of genes to complex traits can be analyzed with genome-wide profiling. In a discovery sample, a genetic risk profile for depression was defined based on a GWA study of 1738 adult cases and 1802 controls. The genetic risk scores were tested in two population-based samples of elderly participants. The genetic risk profiles were evaluated for depression and anxiety in the Rotterdam Study cohort and the Erasmus Rucphen Family (ERF) study. The genetic risk scores were significantly associated with different measures of depression and explained up to ∼0.7% of the variance in depression in Rotterdam Study and up to ∼1% in ERF study. The genetic score for depression was also significantly associated with anxiety explaining up to 2.1% in Rotterdam study. These findings suggest the presence of many genetic loci of small effect that influence both depression and anxiety. Remarkably, the predictive value of these profiles was as large in the sample of elderly participants as in the middle-aged samples.

11ß-hydroxysteroid dehydrogenase type 1 gene expression is increased in ascending aorta tissue of metabolic syndrome patients with coronary artery disease.

11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD-1) activity and mRNA levels are increased in visceral and subcutaneous adipose tissues of metabolic syndrome subjects. We analyzed 11ß-HSD-1 expression in human epicardial adipose (EA) and ascending aorta (AA) tissues of metabolic syndrome patients and examined their contribution to the development of coronary atherosclerosis. The 11ß-HSD-1 expression was evaluated by qRT-PCR in EA and AA tissues of 20 metabolic syndrome patients with coronary artery disease (metabolic syndrome group) and 10 non-metabolic syndrome patients without coronary artery disease (controls). 11ß-HSD-1 expression was increased in EA and AA tissues of the metabolic syndrome group (4.1- and 5.5-fold, respectively). A significant positive correlation was found between 11ß-HSD-1 expression in EA tissue and waist hip ratio and 11ß-HSD-1 expression in AA tissue and body mass index, while a negative correlation was found between 11ß-HSD-1 expression in EA tissue and HDL. Expression of CD68, a macrophage marker, was significantly increased in both tissues of the metabolic syndrome group; it was 2-fold higher in AA tissue compared to EA tissue in the metabolic syndrome group. Our findings of increased expression of 11ß-HSD-1 and CD68 in AA tissue of the metabolic syndrome group lead us to suggest that they contribute to coronary atherosclerosis in metabolic syndrome. This positive correlation between obesity markers and 11ß-HSD-1 in AA and EA tissues strengthens the evidence that 11ß-HSD-1 has a role in metabolic syndrome. To the best of our knowledge, this is the first report showing 11ß-HSD-1 and CD68 expression in AA tissue of metabolic syndrome patients. We suggest that there is tissue-specific expression of 11ß-HSD-1 in metabolic syndrome and associated cardiovascular disorders.

Association between perceived and objective hand-wrist function in distal radius fracture.

The relationship between patient-reported outcome measures and objective measures is important for understanding patient expectations. The aim of this study was to investigate the relationship of each section of the Michigan Hand Outcomes Questionnaire (MHQ) to objective measurements in patients with distal radius fracture (DRF). Eighty-four patients who were treated operatively or non-operatively for DRF were included. Injury severity was assessed by the Modified Hand Injury Severity Score. Joint motion was assessed at 6 and 12 weeks and grip strength at 12 weeks after non-operative treatment or surgery. The MHQ was used to assess hand functionality. The relationships between measurements were analyzed by Spearman correlation analysis. Statistical significance was set at p < 0.05. Fifty-one patients (60.7%) were women and 33 (39.3%) men. Mean age was 48.17 ± 12.26 (range, 20-64) years. Fifty-two (61.9%) patients were treated surgically and 32 (38.1%) non-operatively. Forearm pronation-supination and wrist flexion and ulnar deviation at week 6 and forearm pronation-supination, wrist extension and radial deviation at week 12 correlated with MHQ scores, unlike wrist extension and radial deviation at week 6 and flexion and ulnar deviation at week 12. Gross and fine grip strength at week 12 correlated with MHQ, except for the overall hand function, work performance and pain subsections. The MHQ subsections correlated with joint motion and grip strength in the early period after DRF. These findings clarified patient expectations in the early period.

Glutathione S-transferase P1 polymorphisms are associated with time to tumor progression in small cell lung cancer patients.

PURPOSE: Many of commonly used chemotherapeutics in lung cancer treatment are metabolized by glutathione-S transferases (GSTs). The placental isoform of GST (GSTP1) is the most abundant isoform in the lung. Polymorphisms within the GSTP1 may result in alterations in enzyme activity and change sensitivity to platinum-based chemotherapy. We investigated whether the polymorphism within the exons 5 and 6 of GSTP1 gene may change response to therapy, time to tumor progression (TTP) and overall survival in small cell lung cancer (SCLC) patients. METHODS: Ninety-four histologically confirmed patients with SCLC were enrolled in this study during 1995-2006. GSTP1 Ile105Val polymorphism in exon 5 and GSTP1 Ala- 114Val polymorphism in exon 6 were determined by using PCR-RFLP techniques. Associations between the GSTP1 polymorphisms and treatment response were evaluated using the chi-square test. Associations between the GSTP1 polymorphisms and TTP and overall survival were compared using Kaplan-Meier survival curves. RESULTS: We found no significant associations between exon 5 and exon 6 GSTP1 gene polymorphisms and response to therapy or overall survival. Patients carrying both variant exon 5 (Ile/Val or Val/Val) and variant exon 6 (Ala/Val) genotypes had significantly shorter TTP (5 vs. 8 months, p = 0.04). Moreover, patients with heterozygote exon 6 variant had presented with extensive-stage disease. CONCLUSION: No individual effect of variant alleles was found in relation to chemotherapy response, median TTP and overall survival. The carriage of both types of variant alleles may predict worse outcome.

The ovarian and uterine arteries in the chinchilla (Chinchilla lanigera).

The purpose of this study was to describe arteries supplying the ovaries and uterus in the chinchilla. Five healthy adult female chinchillas were used. In order to reveal the arterial network by dissecting under a stereoscopic microscope, latex coloured with red ink was injected through the common carotid artery. The ovaries of the chinchilla are supplied by the arteriae ovaricae which formed end-to-end anastomoses with the cranial termination of the arteria uterina. Soon after leaving the aorta abdominalis, the arteriae ovaricae extended 2-3 mm caudolaterally, then released 1 branch and extended caudally and bifurcated into 2 further branches. One of these supplied branches to fat tissue. The other branch coursed caudally and anastomosed with the arteria circumflexa ilium profunda and dispersed into fat tissue. The arteria ovarica further subdivided into 2 rami ovaricae. The origins of the uterine arteries were exclusively from the left arteria iliaca externa. The arteria uterina gave a branch to the arteria umbilicalis and consecutive branches which supplied to the ureter, urinary bladder and cranial aspects of the vagina. It also gave rise to 2-3 branches to the cervix and further supplied 10-12 meandering branches to the uterine horns. The arteria uterina gave rise to many tortuous arteries to the uterus and provided 2 further branches to the ovary.

Seroreactivity against PTEN-induced putative kinase 1 (PINK1) in Turkish patients with Behçet's disease.

BACKGROUND: Behçet's disease (BD) is a multisystem inflammatory disorder characterized by recurrent oral ulcers, genital ulcers and ocular inflammation, as well as skin, joint, vascular, pulmonary, central nervous system (CNS) and gastrointestinal tract manifestations. The etiopathogenesis of BD has not yet been identified; but it has generally been accepted that several environmental factors may induce an inflammatory attack in genetically susceptible individuals. In this study, we aimed to identify antigens that could elicit high-titer IgG responses by the serological analysis of recombinant expression of cDNA libraries method (SEREX). METHODS: We screened a human testis cDNA library with pooled sera obtained from 4 BD patients by SEREX. Antigens that were identified with the initial analysis were selected for seroreactivity analysis of a larger group of BD patients (n=78) and controls (n=66) by serological immunoscreening. RESULTS: We observed seroreactivity against 6 antigens using the pooled sera. These included rabaptin 5 (RABPT5), PTEN-induced putative kinase 1 (PINK1), switch associated protein 70 (SWAP70), interferon-induced protein with tetratricopeptide repeats 2 (IFIT2), ankyrin repeat domain 20 family, member A1 (ANKRD20A1), and an unknown antigen. Eleven out of 82 (13.4%) BD patients were found to have antibodies elicited against PINK1 antigen, when none of the control sera showed reactivity (p=0.001). There was no significant difference in the frequency of other defined antigens between the patient and control groups. However, among BD clinical sub-groups, anti-SWAP70 antibodies were found to associate with vascular involvement. DISCUSSION: In this study, antibodies against PINK1 were found to specifically associate with BD while SWAP70 antibody was associated with clinical sub-groups of BD. Although variations in both genetic background and environmental factors may affect the outcome of serological responses, our results suggest that serological screening can be used to identify antigens that elicit antibody responses associated with BD.

Do adipofascial flaps affect the mechanical properties of a repaired tendon? A biomechanical rat model study.

The aim of this study was to evaluate the effect of vascularized and non-vascularized fascial flaps on tendon healing, specifically the maximum strain, maximum stress, elasticity and resistance of the repaired tendon. Rats were randomly divided into 3 groups: Group 1 - primary repair; Group 2 - vascularized pedicled fascial graft; Group 3 - non-vascularized free fascial graft. The rats were euthanized after 2 weeks and 40mm-long samples were taken from the Achilles tendon and gastrocnemius muscle. To evaluate the mechanical properties of the tendons, maximum load, maximum deformation, energy stored until yield point and stiffness on the load-deformation curve were measured. Based on this mechanical testing, the best group in terms of tissue strength and quality was the primary repair group. When the samples were examined individually, the two samples with the highest breaking force after the control group were in the pedicled graft group. The worst results overall were in the free graft group. We believe that if the blood flow is preserved for the fascial flap in the pedicled graft group, the tendon's breaking force would be higher.

Gross morphological features of plexus brachialis in the chinchilla (Chinchilla lanigera).

This study documents the detailed features of the morphological structure and the innervation areas of the plexus brachialis in the chinchilla (Chinchilla lanigera). The animals (5 female and 5 male) were euthanased with ketamine hydrocloride and xylazine hydrocloride combination, 60 mg/kg and 6 mg/kg, respectively. Skin, muscles and nerves were dissected under a stereo-microscope. The brachial plexus of the chinchilla is formed by rami ventrales of C5-C8, T1 and T2, and possesses a single truncus. The subscapular nerve is formed by the rami of the spinal nerves originating from C6 (one thin ramus) and C7 (one thick and 2 thin rami). These nerves innervate the subscapular and teres minor muscles. The long thoracic nerve, before joining with the brachial plexus, obtains branches from C6 and C7 in 5 cadavers (3 male, 2 female), from C7 in 4 cadavers (2 male, 2 female) and from C6-C8 in only 1 female cadaver. These nerves disperse in variable combinations to form the extrinsic and intrinstic named, nerves of the thoracic limb. An undefined nerve branch originates from the rami ventrales of C7, C8 and T1 spinal nerves enter the coracobrachial muscle.

Comparison of Emla cream and lidocaine injection for local anaesthetic before radiofrequency reduction of the inferior turbinates.

We compared the effectiveness of local anaesthetic with Emla cream with that of an injection of lidocaine for radiofrequency reduction of the inferior turbinates. We studied 98 consecutive patients with hypertrophied inferior turbinates, 46 of whom were given Emla cream and 52 lidocaine injection. The procedure began five minutes after the injection of lidocaine and 10minutes after the Emla cream had been applied. Patients were asked to indicate on a visual analogue scale (VAS) the degree of perioperative pain, anxiety, sensation of choking, and discomfort on swallowing that they felt after the procedure. Patients treated with Emla had significantly lower VAS scores for discomfort on swallowing than those treated with lidocaine (p=0.001), but there were no other significant differences between the two groups. We conclude that Emla cream is an efficacious alternative to infiltration of lidocaine for radiofrequency reduction of the inferior turbinates.

Gross morphological features of the lung and air sac in the Japanese quail.

This study was conducted to reveal the morphological characteristics of the lung and air sacs in Coturnix coturnix japonica (Japanese quails). Ten quails were allocated into two groups. Tracheas of 5 quails with neoprene latex and 5 quails with methylmetacrylate were injected to fill the trachea and air sacs. Latex embalmed animals were stored in 10% formaldehyde solution for two months. Animals given methylmetacrylate were maserated in 30% potassium hydroxide at 40 degrees C for two days. Lungs were located in the dorsal part of the thorax and very close to the thoracic vertebrae and ribs. Shorter than the dorsal border, the ventral border lied between the 3rd and 6th ribs. Cervical, clavicular, cranial thoracic, caudal thoracic and abdominal sacs were identified. These sacs had connection with the 3rd, 4th and 5th lateroventral and 4th mediolateral bronchi. Saccus cervicalis was located on the left and right portions of the vertebrae cervicales et thoraricae with a pronounced communication ventromedially. However, the cervical sac aeration of only all cervical vertebrae was present in this study. Humerus was a non-aerated bone. Pneumatic foramen was absent and did not aerate the sternum. Cranial thoracic sac connected to the 1st, 2nd and 4th medioventral bronchi and gave no diverticulum for aeration. Cranial thoracic sac received air through the 4th medioventral and the 1st and 2nd lateroventral bronchi. Left and right abdominal air sacs paramedially produced diverticulum femorale, but this diverticulum did not enter the femur.

Humeral shaft fractures and radial nerve palsy: early exploration findings.

OBJECTIVES: This study aims to present the results of early nerve explorations in cases with radial nerve palsy associated with humeral shaft fracture and to investigate in which cases early nerve explorations may be beneficial. PATIENTS AND METHODS: Twenty-four patients (17 males, 7 females; mean age 36 years; range 18 to 72 years) with complete sensory and motor radial nerve damage associated with humeral shaft fracture were retrospectively analyzed. The patients with high-energy trauma and the ones who had spiral and segmental fractures with low energy traumas were included in the study. Early nerve exploration was performed in all patients within an average of 4.8 days (range 1 to 20 days) after fracture development. Electrophysiological assessments were performed in cases with no neurological recovery until 12th week. RESULTS: Spiral fractures of the humerus shaft observed in 14 (58.3%) of the 24 operated patients were the most common fracture type, followed by transverse fracture in four patients (16.6%) and comminuted fracture in two patients (8.3%). As a result of the exploration, we observed nerve compression between the fracture fragments in seven patients (29.1%); a majority of these patients (n=6) had spiral fractures of humerus and one patient had comminuted fracture. One patient with a spiral type fracture had nerve transection. Radial nerve function recovered in most of the patients (95.8%). Average duration for fracture union was 6.7±3.8 months (range 3 to 18 months). CONCLUSION: Spiral fractures of humerus, particularly with wedge fragment, may be a candidate for early surgical exploration. Early exploration may be beneficial in terms of early identification of neural injury in patients with radial nerve dysfunction associated with spiral and comminuted humerus fracture.

Anatomical structure of the brachial plexus in the merlin (Falco columbarius).

This study aimed to document the detailed features of the morphological structure and the innervation areas of the brachial plexus in Merlin (Falco columbarius). The skin and muscles of five adult male Merlins were dissected under the stereo microscope. The Merlin had two plexus trunks. The accessory brachial plexus consisted of ventral rami C10 and C11. C11 was divided into two branches: the cranial and caudal. The brachial plexus was composed of a rather complex network involving the ventral rami of C11-C13, T1 and T2. In addition, a thin branch from the last two cervical sympathetic nerves participated in the plexus formation. C12, C13 and T1 had rather thick trunk. C12, C13 and T1 were also involved in the formation of the brachial plexus emerging after 1 cm from the foramen inter-vertebrale as three trunk roots.

Collagen membrane wrapping around methotrexate-containing calcium-phosphate cement reduces the side effects on soft tissue healing.

OBJECTIVES: This study aims to evaluate whether the collagen membrane (membrane) wrapping around the methotrexate (MTX)-containing calcium-phosphate cement (CPC) reduces the side effects on soft tissue healing. MATERIAL AND METHODS: In 36 rats, femoral bone defects were created and treated in six groups which were CPC only, CPC and membrane wrapping around, CPC containing 2% MTX, CPC containing 2% MTX and membrane wrapping around, CPC containing 5% MTX, CPC containing 5% MTX and membrane wrapping around. RESULTS: Histological examinations revealed a statistically significantly improved healing in the connective tissue samples of the CPC containing 5% MTX group wrapped around by membrane compared to those without membrane (p=0.04). However, this was not seen in other groups. CONCLUSION: Membrane wrapping around the CPC containing MTX reduces the side effect of MTX on cellular proliferation at its highest concentration, particularly. Membrane wrapping may allow administration of higher doses of an anti-neoplastic drug which can be more effective.

Renal expression and functions of aquaporin 1 and aquaporin 4 in cattle.

Aquaporin (AQP) 1 and AQP 4 are members of the aquaporin water channel family that play an important role in reabsorption of water from the renal tubular fluid to concentrate urine. Studies of renal AQPs have been performed in human, rodents, sheep, dogs and horses. We studied nephron segment-specific expression of AQP 1 and AQP 4 using immunohistochemical staining on paraffin sections of bovine kidneys. AQP 1 was moderately expressed in endothelium of the cortical capillary network, vasa recta, and glomerular capillaries. AQP 4 was moderately expressed only in cytoplasm of epithelial cells in proximal tubules. We concluded that AQP 1 and AQP 4 in the bovine kidney showed some differences from other species in renal trans-epithelial water transport.