Evaluation of a five-year Bloomberg Global Road Safety Program in Turkey.

OBJECTIVE: Turkey was included in the Bloomberg Philanthropies funded Global Road Safety Program (2010-14) with Ankara and Afyonkarahisar (Afyon) selected for interventions to manage speed and encourage seat-belt use. The objectives of this study are to present the monitoring and evaluation findings of seat-belt use and speed in Afyon and Ankara over the five years and to assess overall impact of the program on road traffic injury, and death rates in Turkey. STUDY DESIGN: Quasi-experimental before after without comparison. METHODS: In collaboration with the Middle East Technical University, roadside observations and interviews were coupled with secondary data to monitor changes in risk factors and outcomes at the two intervention sites. RESULTS: The percentage of seat-belt use among drivers and front-seat passengers in Afyon and Ankara increased significantly between 2010 and 2014 with increased self-reported use and preceded by an increase in tickets (fines) for not using seat belts. There were uneven improvements in speed reduction. In Afyon, the average speed increased significantly from 46.3 km/h in 2012 to about 52.7 km/h in 2014 on roads where the speed limits were 50 km/h. In Ankara, the average speed remained less than 55 km/h during the program period (range: 50-54 km/h; P < 0.005) for roads where the speed limits were 50 km/h; however, the average speed on roads with speed limits of 70 km/h decreased significantly from 80.6 km/h in 2012 to 68.44 km/h in 2014 (P < 0.005). CONCLUSION: The program contributed to increase in seat-belt use in Afyon and Ankara and by drawing political attention to the issue can contribute to improvements in road safety. We are optimistic that the visible motivation within Turkey to substantially reduce road traffic injuries will lead to increased program implementation matched with a robust evaluation program, with suitable controls.

Using PVA and TPGS as combined emulsifier in nanoprecipitation method improves characteristics and anticancer activity of ibuprofen loaded PLGA nanoparticles.

In the preparation of nanoparticles (NPs) by the nanoprecipitation method, emulsifiers play a key role for NPs' characteristics. The present study aimed to investigate the combined emulsifier effect on ibuprofen loaded poly(lactic-co-glycolic acid) (PLGA) NPs' characteristics and anticancer activity. Ibuprofen loaded PLGA NPs were prepared by nanoprecipitation using different concentrations of PVA (poly(vinyl alcohol)) or PVA-TPGS (d-α-tocopherol polyethylene glycol 1000 succinate) combination as emulsifier. It was found that encapsulation efficiencies of NPs varied between 17.9 and 41.9 % and the highest encapsulation efficiency was obtained with 0.5% PVA + 0.1% TPGS (coded as PLGA PVA/TPGS NPs). PLGA PVA/TPGS NPs were characterized and compared with PLGA PVA NPs, which was obtained by 0.5% PVA alone. Polydispersity index of PLGA PVA/TPGS and PLGA PVA NPs were found to be 0.08 and 0.15, respectively. Incorporation of TPGS with PVA slightly decreased the initial ibuprofen release. Transmission electron microscopy analyses demonstrated a nearly uniform particle size distribution and spherical particle shape of the PLGA PVA/TPGS NPs. Additionally, PLGA PVA/TPGS NPs were significantly more cytotoxic than PLGA PVA NPs on the MCF-7 (human breast adenocarcinoma cells) and Caco-2 (human epithelial colorectal adenocarcinoma) cells (p<0.05). Also PLGA PVA/TPGS NPs were not cytotoxic on normal cells (L929, mouse healthy fibroblast cells) (p>0.05). In conclusion, these results indicated that using a combination of TPGS and PVA as an emulsifier in nanoprecipitation could be a promising approach for preparing ibuprofen loaded PLGA NPs because of their improved characteristics and anticancer activity.

Association of MDR1 C3435T and C1236T single nucleotide polymorphisms with male factor infertility.

Infertility affects 1 in 6 couples and approximately 1 in 25 men. Male factor infertility is a major cause of spermatogenic anomalies, the causes of which are largely unknown. Impaired repro-ductive functions in men might result from physiological, genetic, and/or environmental factors such as xenobiotics. The multi-drug re-sistance1 (MDR1) gene encodes a P-glycoprotein which has a role in the active transport of various substrates providing protection of somatic cells from potentially toxic substances, including xenobi-otics. MDR1 is highly expressed at the luminal surface of capillary endothelial cells, and is expressed in Leydig cells, testicular mac-rophages, and Sertoli cells. We performed genotype and haplotype analyses of MDR1 in 192 infertile and 102 fertile Turkish men for the genetic markers C1236T and C3435T, using polymerase chain reaction-restriction fragment length polymorphism analysis. In the overall population, correlations were analyzed in all genotype mod-els. We found that the C3435T polymorphism TT vs CT genotypes showed statistically significant differences in their association with infertility (P = 0.045), and that the CT genotype was associated with high sperm DNA damage (P = 0.02), suggesting that the CT genotype might be a susceptibility factor for infertility. Additionally, the T-T haplotype was significantly more frequent in the control group (13.2 vs 6.5%; odds ratio = 0.459, 95%CI = 0.259-0.814, P = 0.006). This study showed that MDR1 might have a role in male infertility. Fur-ther research in large cohorts with different populations is required to clarify the role of MDR in male fertility.

Endometriosis of episiotomy scar: a case report.

Endometriosis is characterized by the presence of histologically normal endometrial glands and stroma outside the uterine cavity. Endometriosis predominantly locates on peritoneal surfaces, but it also affects the vagina, vulva, and perineum, usually secondary to surgical or obstetric trauma. Endometriosis in an episiotomy scar is a fairly rare phenomenon. The authors present a case of endometriosis in an episiotomy scar.

Transcriptome Analysis of Beta-Catenin-Related Genes in CD34+ Haematopoietic Stem and Progenitor Cells from Patients with AML.

Background: Acute myeloid leukaemia (AML) is a disease of the haematopoietic stem cells(HSCs) that is characterised by the uncontrolled proliferation and impaired differentiation of normal haematopoietic stem/progenitor cells. Several pathways that control the proliferation and differentiation of HSCs are impaired in AML. Activation of the Wnt/beta-catenin signalling pathway has been shown in AML and beta-catenin, which is thought to be the key element of this pathway, has been frequently highlighted. The present study was designed to determine beta-catenin expression levels and beta-catenin-related genes in AML. Methods: In this study, beta-catenin gene expression levels were determined in 19 AML patients and 3 controls by qRT-PCR. Transcriptome analysis was performed on AML grouped according to beta-catenin expression levels. Differentially expressed genes(DEGs) were investigated in detail using the Database for Annotation Visualisation and Integrated Discovery(DAVID), Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes(KEGG), STRING online tools. Results: The transcriptome profiles of our AML samples showed different molecular signature profiles according to their beta-catenin levels(high-low). A total of 20 genes have been identified as hub genes. Among these, TTK, HJURP, KIF14, BTF3, RPL17 and RSL1D1 were found to be associated with beta-catenin and poor survival in AML. Furthermore, for the first time in our study, the ELOV6 gene, which is the most highly up-regulated gene in human AML samples, was correlated with a poor prognosis via high beta-catenin levels. Conclusion: It is suggested that the identification of beta-catenin-related gene profiles in AML may help to select new therapeutic targets for the treatment of AML.

Analysis of risk factors for cancer-specific survival in neoadjuvant chemotherapy nonresponsive disease of muscle-invasive bladder cancer: A multicentre study from the Turkish Urooncology Association Bladder Tumor study group.

OBJECTIVE: To investigate the risk factors affecting cancer-specific survival (CSS) in nonresponsive disease to neoadjuvant chemotherapy (NAC) among patients with muscle-invasive bladder cancer (MIBC) who were treated with NAC and radical cystectomy (RC). METHODS: Patients with MIBC who underwent NAC and RC were retrospectively examined. By comparing clinical and pathological stages, patients whose pathological stage was lower than clinical stage were categorized as "NAC-responsive" and the remainder as "NAC-non-responsive." Apart from pathologic staging, variables compared between groups included age, gender, Eastern Cooperative Oncology Group (ECOG) score, clinical stages, NAC type and cycle number, durations between MIBC diagnosis and NAC initiation and RC, presence of hydronephrosis, number of lymph nodes removed, and variant histology of urothelial bladder cancer. CSS analysis was performed by construction of Kaplan-Meier survival curves and multivariable Cox regression was performed to identify the prognosticators in the NAC-non-responsive-group. RESULTS: Ninety-two patients were included with a mean age was 61.5 ± 8.5 years, of whom 84.8% were men. The NAC regimen used was predominantly gemcitabine-cisplatin (88%) and the median cycle number was 4. Fifty-six (60.9%) patients were NAC-non-responsive. There was a significantly lower proportion of patients receiving ≥4 cycles (46.4% vs. 66.7%) and a higher rate of patients with ECOG score ˃1 (33.9% vs. 11.1%) in the NAC-non-responsive-group compared to the NAC-responsive-group (both P < 0.05). Other variables were similar between groups. In multivariable analysis, only ypN+ was found to be an independent prognosticator for CSS in NAC-non-responsive-group (HR: 2.725, CI95%:1.017-7.303). CONCLUSION: Although higher ECOG scores and lower cycle numbers appears to be associated factors in NAC-non-responsive disease, only ypN(+) status was a prognosticator for CSS in this population.

Effect of L-carnitine on the synthesis of nitric oxide in RAW 264·7 murine macrophage cell line.

L-Carnitine (ß-hydroxy-γ-trimethyl aminobutyric acid) plays a critical role in inflammatory diseases by modulating inflammatory cell functions. Inducible nitric oxide synthase (iNOS), a proinflammatory enzyme responsible for the generation of nitric oxide (NO), has been implicated in the pathogenesis of inflammatory diseases. Mechanism of action of L-carnitine on inflammation via iNOS and nuclear factor κB (NF-κB) is unclear. In this study, we aimed to investigate the effect of L-carnitine on nitric oxide synthesis in lipopolysaccharide (LPS)-stimulated RAW 264·7 macrophage cells. For this purpose, cells were pretreated with various concentrations of L-carnitine and subsequently incubated with LPS (1 µg·ml(-1) ). NO levels, iNOS protein expression, and NF-κB activity were determined using colorimetric detection, Western blotting and transfection assays. Our results showed that treatment with L-carnitine suppressed nitric oxide production, iNOS protein expression and NF-κB activity. We demonstrated that inhibitory effect of L-carnitine on iNOS protein expression is at transcriptional level. This study may contribute to understanding the anti-inflammatory effect of L-carnitine.

Effect of combined exercise training on serum brain-derived neurotrophic factor, suppressors of cytokine signaling 1 and 3 in patients with multiple sclerosis.

BACKGROUND: Suppressors of cytokine signaling (SOCS) and brain-derived neurotrophic factor (BDNF) are important immunologic, and neurotrophic factors for MS pathogenesis. The impact of exercise on these factors is yet to be fully elucidated in patients with MS. OBJECTIVE: The primary aim of this study is to investigate the effect of 8-week combined exercise training on serum concentrations of SOCS1, SOCS3, and BDNF. The secondary aim is to determine the effects of combined exercise training on balance, functional exercise capacity, and fatigue in patients with MS. METHODS: Serum SOCS1, SOCS3, and BDNF levels were assessed in 36 MS patients and 18 healthy individuals. In addition, balance, functional exercise capacity, and fatigue were assessed in the patients with MS. The patients were randomly divided into the combined exercise group (MS-EX, n:18) and the control group (MS-C, n:18). MS-EX received an 8-week combined exercise training. RESULTS: The serum SOCS1, SOCS3, and BDNF levels were similar in the MS patients and healthy control (HC). In MS-EX, the serum BDNF level, balance, functional exercise capacity, and fatigue improved after 8weeks (p<0.05), but the serum SOCS1, and SOCS3 levels did not change significantly (p>0.05). In MS-C, the serum SOCS1 level, and fatigue increased significantly after 8weeks (p<0.05), but serum SOCS3, BDNF, balance and functional exercise capacity did not change (p>0.05). CONCLUSIONS: In summary, the combined exercise training improved BDNF, and physical performance in patients with MS. But, future studies are needed to clarify the role of SOCS proteins in MS pathogenesis and the effect of exercise on SOCS.

Effect of Saccharomyces boulardii in children with acute gastroenteritis and its relationship to the immune response.

We evaluated the effect of Saccharomyces boulardii administration in otherwise healthy children aged between 6 months and 10 years who were admitted for acute diarrhoea (15 males, 12 females). The patients were randomized into two groups: group 1 (n = 16) received 250 mg S. boulardii dissolved in 5 ml of water orally twice daily for 7 days and group 2 (n = 11) received placebo. Clinical and laboratory assessments were performed on admission and on day 7 of follow-up. Both groups experienced reduced daily stool frequency, the decrease being significantly greater in group 1 on days 3 and 4 compared with group 2. Group 1 demonstrated significant increases in serum immunoglobulin A and decreases in C-reactive protein levels on day 7. The percentage of CD8 lymphocytes on day 7 was significantly higher in group 1 than group 2. This study confirmed the efficacy of S. boulardii in paediatric acute gastroenteritis and the findings suggest that S. boulardii treatment enhances the immune response.

Replantation of thumb avulsion injuries.

PURPOSE: To point out detailed technical considerations and tactical modifications within the experience of 59 replantations of thumb avulsion injuries, to clarify the indications of replantation, and to evaluate the long-term results. PATIENTS AND METHODS: Seventy-two thumb avulsions of 510 thumb amputations were treated at our centre between 1986 - 2002. Sixty-two of them were male and 10 were female. The average age of the patients was 27 years. Fifty-nine avulsed thumbs were replanted, and 13 were considered as "not replantable" and operated using other reconstructive procedures. Since the main goal of thumb replantation is survival with sensitivity and good function, all the injured tissues were repaired or primarily reconstructed. As a main principle, we always aimed for a one-stage reconstruction including vein grafts for the arterial injury, direct vein repair or vein transfer to establish venous outflow, tendon transfers to restore movement, and nerve transfer to restore sensation. RESULTS: Overall survival rate was 84.7 %. The average follow-up time was 65.2 months. 80 percent of the patients returned to their original work within an average of 4 months after replantation. The patients were generally satisfied with the outcome and ability to use their thumb. The average range of movement of the interphalangeal joint was 75 % of the normal side. On average, key pinch strength was 65 % of contralateral hand. Two-point discrimination was less than 10 mm in 60 % of the cases. Semmes-Weinstein monofilament testing evaluation showed 2.83 in 35 patients, 3.61 in 20, and 6.68 in 4 patients. CONCLUSIONS: In replantation of avulsion amputation of the thumb, functional success depends on repair or reconstruction of all damaged tissues, if necessary, using nerve transfers and tendon transfers. If these could be done primarily as a one-stage reconstruction, the costs would be less, the patients would return to their work when the one-stage treatment and rehabilitation is finished, and would also eliminate the technical difficulties encountered in secondary reconstructions.

Liver transplantation of a child with child a cirrhosis and severe hepatopulmonary syndrome.

Hepatopulmonary syndrome (HPS) is a clinical state defined by a chronic hepatic disorder, intrapulmonary vascular dilatation, and altered gas exchange resulting in hypoxemia. Cirrhosis of the liver is the most common condition associated with HPS. A 3-year-old boy who presented with end-stage liver disease and severe hepatopulmonary syndrome underwent orthotopic liver transplantation (OLT). The findings of HPS resolved immediately after OLT. His status is within normal limits at 6 months after liver transplantation.

Improving estimation of corneal refractive power by measuring the posterior curvature of the cornea.

We developed a formula to measure the posterior curvature of the cornea. In our study, real corneal power in 51 eyes was calculated by using anterior and posterior curvatures and corneal thickness. The corneal refractive index was found to be a variable value between 1.3243 and 1.3339 (mean 1.3304 +/- 0.0003).

Vigabatrin has an anxiolytic effect in the elevated plus-maze test of anxiety.

tau-Vinyl GABA (vigabatrin, GVG) is a novel antiepileptic drug that irreversibly inhibits GABA transaminase and elevates GABA levels in all parts of the brain. In the present study, we investigated the anxiolytic and behavioral effects of GVG in the elevated plus-maze and the hole board compared to diazepam. Doses of 500 and 1,000 mg/kg GVG were injected IP to different groups of male Wistar rats and animals were tested either 4 or 24 h after injection. Animals administered diazepam (1.5 mg/kg, IP) and saline (1 ml) were tested 20 min after injection. GVG and diazepam were found to decrease significantly the number of squares visited and rearing; both had a suppressant effect on locomotor activity. Neither drug had an effect on exploration (head dipping). GVG at a dose of 1,000 mg/kg was shown to have a similar anxiolytic activity either after 4 or 24 h as diazepam, while GVG at 500 mg/kg did not show any significant anxiolytic effect.

Comparison between sensitive and nonsensitive free flaps in reconstruction of the heel and plantar area.

In this study, 12 cases of reconstruction of the heel and plantar area since 1982 are reviewed. Six nonsensate muscle free flaps and six sensate fasciocutaneous flaps were used, respectively. Categories assessed were the time interval for return to daily living activities, sensation to light touch, pinprick, Semmes-Weinstein monofilament test of the reconstructed area for sensory evaluation; and results of pedograms (maximal pressure, pressure distribution, and total contact area of the plantar surface). Follow-up periods were between 2 and 14 years, with an average of 6 years. Better sensory results and early return to daily living activities were observed in the sensate flap group, but the defects were smaller in this group. Despite the slightly longer time to return to daily living activities and worse sensory results, long-term follow-up showed that patients with nonsensate flaps had no difficulty in performing living activities if they continued to be careful and to use some kind of protective shoes. The results of the pedogram analyses were similar between the two groups with regard to total contact area of the reconstructed foot in relation to the healthy foot. Pressure values of the reconstructed areas in sensate flaps were found to be close to pressure values in the same weight areas of the normal foot. The differences between pressure values of the sensate and nonsensate flaps were statistically significant (p < 0.001). Therefore, in reconstruction of the weight-bearing surface of the foot, each case should be evaluated individually. The reconstructive method should be chosen according to the location and soft-tissue requirements of the defect.

Gliadin-specific IgA antibodies in breast milk.

Breast-feeding helps to protect against coeliac disease because of the presence of antigliadin-IgA antibodies (AGA-IgA) in breast milk. The aim of this study was to assess the concentrations of AGA-IgA in breast milk during lactation, and whether these concentrations vary with the socioeconomic status of the women. Samples of serum for determination of IgA albumin and AGA-IgA, and samples of breast-milk for AGA-IgA were collected from 105 healthy mothers (aged 17 - 36 years). Women were divided into two groups: group 1 were of low and group 2 were of high socioeconomic status. No differences were observed between the study parameters in the two groups. Serum AGA-IgA in both groups was, however, significantly lower than that in colostrum. AGA-IgA concentrations in both groups gradually decreased during 45 days of lactation; the difference between colostrum and the samples taken at days 10 and 30 - 45 of lactation was significant. The encouragement of sufficient and long-term (e.g. 4 - 6 months) breast-feeding seems likely to be beneficial in preventing coeliac disease.

Brachioradialis re-routing for the restoration of active supination and correction of forearm pronation deformity in cerebral palsy.

A brachioradialis muscle rerouting procedure was used to restore active supination in five children with cerebral palsy and a pronation deformity. Following release and lengthening of the pronator quadratus and pronator teres muscles, respectively, the brachioradialis tendon was divided as a Z plasty and the distal part of the tendon was passed through the interosseous space in a dorsal to palmar direction, and then sutured to its proximal end. The procedure resulted in a gain of 81 degrees of active supination.

Rabdomyosarcoma of the biliary tree.

Rabdomyosarcoma of the biliary tree is one of the rare causes of biliary tract obstruction in childhood. Nevertheless it is the most common cause of obstructive jaundice due to neoplastic biliary obstruction. We present a two-year-old child with obstructive jaundice secondary to an embryonal rhabdomyosarcoma of the biliary tree. She underwent surgery and, after total excision of the mass, a hepaticojejunostomy and Roux-en-Y anastomosis were performed. She was referred to the Pediatric Oncology Group for follow-up. Rhabdomyosarcoma of the bilary tree, although rare, must be considered in the etiology of obstructive jaundice in children.

Brachialis muscle transfer to the forearm for the treatment of deformities in spastic cerebral palsy.

The use of the brachialis muscle for tendon transfers in cerebral palsy has not been described previously. In this study, the brachialis muscle was used for transfer in 11 patients with spastic cerebral palsy for the restoration of forearm supination, wrist extension, or finger extension. Four patients underwent brachialis rerouting supinatorplasty. Active supination increased in two (60° and 50°), minimally increased in one (5°), and did not change in one patient. Five patients had a brachialis to extensor carpi radialis brevis transfer. The mean gain in postoperative active wrist extension was 65°. Two patients with finger flexion deformity and no active metacarpophalangeal joint movement underwent a brachialis to extensor digitorum communis transfer, and they attained an improved posture of finger extension although their postoperative metacarpophalangeal flexion-extension movement arc was 5° and 25°. None of the patients developed any loss of active flexion at the elbow. Our preliminary experience suggests that the brachialis muscle may serve as an alternative tendon transfer in cerebral palsy.

Blood and tissue nitric oxide and malondialdehyde are prognostic indicators of localized prostate cancer.

OBJECTIVES: Our objective was to examine blood and tissue levels of nitric oxide (NO) and malondialdehyde (MDA), and their correlations with well-known prognostic indicators [total prostate-specific antigen (tPSA), %free/total PSA (%f/t PSA), pathological stage (pT), and Gleason sum] in patients who had radical retropubic prostatectomy (RRP) for localized prostate cancer (PCa) without metastasis. PATIENTS AND METHODS: Preoperatively 31 patients' bloods were obtained for determination of NO, MDA, fPSA, tPSA, and %f/tPSA ratios. Tissues were obtained from RRP specimens for determination of NO and MDA. Gleason sum was assigned for each patient, and pT was determined according to 2002 TNM staging system. pTs were as follows: 10 pT2a, 7 pT2b, 8 pT2c, 4 pT3a, and 2 pT3b. Gleason sum of the PCa in the RRP specimens was as follows: 5 in 1, 6 in 14, 7 in 14, and 9 in 2 patients. RESULTS: There were strong correlations between blood and tissue levels of NO (r=0.83, p<0.001) and MDA (r=0.63, p<0.001), between serum NO and plasma MDA (r=0.88, p<0.001), and finally between tissue NO and tissue MDA (r=0.83, p<0.001). There was also a significant (p<0.05) relationship between all well-known prognostic indicators of PCa (tPSA, %f/tPSA, Gleason sum, and pT) and blood and tissue NO and MDA levels, with single exception of correlation between tissue MDA and Gleason sum (p=0.073). CONCLUSION: Clinically appropriate correlations shown in this study indicates that NO and MDA may be used for prognostic assessment of localized PCa, especially if supported with other well-designed studies including higher number of patients through multi-institutional collaboration.