Suitability of foramen magnum measurements in sex determination and their clinical significance.

BACKGROUND: The foramen magnum provides a transition between fossa cranii posterior and canalis vertebralis. Medulla oblongata, arteria vertebralis and nervus accessorius spinal part pass through the foramen magnum. In this study, we aimed to make the morphometric measurements of the foramen magnum on computed tomography (CT) and to determine the feasibility of sex determination based on these measurements. Besides sex determination, from a clinical aspect, it is important to know the measurements of the foramen magnum in the normal population in terms of diseases characterised by displacement of the posterior fossa structures through foramen magnum to upper cervical spinal canal such as Chiari malformations and syringomyelia. MATERIALS AND METHODS: All the data for our study was obtained retrospectively from 100 patients (50 males, 50 females) who had a CT scan of the head and neck region in Adnan Menderes University Hospital, Department of Radiology. To examine the foramen magnum in each and every occipital bone, we measured the foramen magnum's anteroposterior diameter, transverse diameter, the area of the foramen magnum and its circumference. RESULTS: We found that men have a higher average value than women in our study. According to Student's t-test results; in all measured parameters, there is significant difference between the genders (p < 0.05). When multivariate discriminant function test is performed for all four measurements, the discrimination rate is 64% for all women, 70% for all men and 67% for both genders. CONCLUSIONS: As a result of our study, the metric data we obtained will be useful in cases where the skeletons' sex could not be determined by any other methods. We believe that, our study may be useful for other studies in determining of sex from foramen magnum. Our measurements could give some information of the normal ranges of the foramen magnum in normal population, so that this can contribute to the diagnosis process of some diseases by imaging. (Folia Morphol 2018; 77, 1: 99-104).

Evaluation of pentraxin-3 in familial Mediterranean fever patients during attack and attack-free periods.

INTRODUCTION: Pentraxin-3 (PTX-3) is a prototype of pentraxin proteins that have been shown to be involved in acute phase response. In this study, we aimed to investigate the relationship between PTX-3 levels and familial Mediterranean fever (FMF) disease, and to evaluate PTX-3 as a novel diagnostic marker of FMF. METHOD: Forty-three male patients diagnosed with FMF and 42 healthy individuals were included in the study. Patients with other inflammatory diseases and patients who used drugs having anti-inflammatory properties were excluded from the research. Blood samples were obtained during both attack and attack-free periods. RESULTS: Patient attack periods were confirmed by combining physical examination and elevation of acute phase reactants. Acute phase reactants were significantly higher in attack versus attack-free periods (p < 0.01), however PTX-3 levels were not significantly different between the two periods. Additionally, PTX-3 levels in FMF patients were higher than in controls in both attack (917.29 ± 725.29 vs 451.83 ± 291.95, p < 0.01) and attack-free periods (748.23 ± 487.53 vs 451.83 ± 291.95, p < 0.01). CONCLUSION: In this study, we showed that PTX-3 levels, in both FMF attack and attack-free periods, were significantly higher than in the control group. Finally, PTX-3 may be a promising biomarker for FMF diagnosis and may predict FMF attacks (Tab. 2, Fig. 2, Ref. 18).

An integrated lab-on-a-chip-based electrochemical biosensor for rapid and sensitive detection of cancer biomarkers.

Recent advances in the area of biosensor technology and microfluidic applications have enabled the miniaturisation of the sensing platforms. Here we describe a new integrated and fully automated lab-on-a-chip-based biosensor device prototype (MiSens) that has potential to be used for point-of-care cancer biomarker testing. The key features of the device include a new biochip, a device integrated microfluidic system and real-time amperometric measurements during the flow of enzyme substrate. For ease of use, a new plug and play type sensor chip docking station has been designed. This system allows the formation of an ∼7 µL capacity flow cell on the electrode array with the necessary microfluidic and electronic connections with one move of a handle. As a case study, the developed prototype has been utilised for the detection of prostate-specific antigen (PSA) level in serum that is routinely used as a biomarker for the diagnosis of prostate cancer. The patient samples from a nearby hospital have been collected and tested using the MiSens device, and the results have been compared to the hospital results. The obtained results indicate the potential of the MiSens device as a useful tool for point-of-care testing. Graphical abstract Microfluidics integrated and automated electrochemical biosensor device "MiSens" has been designed and fabricated by a multidisciplinary team and utilised to detect PSA from clinical samples.

Psychological effects of calisthenic exercises on neuroinflammatory and rheumatic diseases.

BACKGROUND: The aim of this study was to evaluate the effects of calisthenic exercises on psychological status in patients with ankylosing spondylitis (AS) and multiple sclerosis (MS). METHODS: This study comprised 40 patients diagnosed with AS randomized into two exercise groups (group 1 = hospital-based, group 2 = home-based) and 40 patients diagnosed with MS randomized into two exercise groups (group 1 = hospital-based, group 2 = home-based). RESULTS: The exercise programme was completed by 73 participants (hospital-based = 34, home-based = 39). Mean age was 33.75 ± 5.77 years. After the 8-week exercise programme in the AS group, the home-based exercise group showed significant improvements in erythrocyte sedimentation rates (ESR). The hospital-based exercise group showed significant improvements in terms of the Bath AS Metrology Index (BASMI) and Hospital Anxiety and Depression Scale-Anxiety (HADS-A) scores. After the 8-week exercise programme in the MS group, the home-based and hospital-based exercise groups showed significant improvements in terms of the 10-m walking test, Berg Balance Scale (BBS), HADS-A, and MS international Quality of Life (MusiQoL) scores. There was a significant improvement in the hospital-based and a significant deterioration in the home-based MS patients according to HADS-Depression (HADS-D) score. CONCLUSION: The positive effects of exercises on neurologic and rheumatic chronic inflammatory processes associated with disability should not be underestimated.

[Transretinal Biopsy of Intraocular Lymphoma]. / Transretinale Biopsie beim intraokularen Lymphom.

BACKGROUND: Intraocular lymphoma is in most cases a diagnostic challenge. Gold standard is a diagnostic vitrectomy. Vitreous biopsy and transretinal biopsies are therefore employed. METHODS: A retrospective analysis was undertaken of all cases of cytological or histological proven intraocular lymphoma between 2002 and the beginning of 2015 in our clinic. RESULTS: The diagnosis of intraocular lymphoma could be established in 16 cases by cytological or histological analysis. Six patients had previously been treated with steroids in the assumption of uveitis. Five of 16 patients had a systemic or CNS lymphoma in their history. The diagnosis of intraocular lymphoma could be made on the basis of a vitreous biopsy in only in 3 cases. In 7 cases an additional vitrectomy with transretinal biopsy was needed. In 1 case a transretinal biopsy was performed initially and in 1 case a re-transretinal biopsy was needed to establish the diagnosis. Two patients underwent iris biopsy to diagnose a secondary metastatic intraocular lymphoma. One amaurotic eye was diagnosed with intraocular lymphoma after enucleation. DISCUSSION: Due to the high relevance for the diagnosis intraocular lymphoma, when a vitreous biopsy was non-informative, a transretinal biopsy should always be considered in cases of retinal or subretinal involvement.

Methylation marker analysis of self-sampled cervico-vaginal lavage specimens to triage high-risk HPV-positive women for colposcopy.

Methylation markers were studied for their suitability to triage human papillomavirus (HPV)-positive women by testing self-collected cervico-vaginal lavage specimens. For this purpose, we analyzed 355 hrHPV-positive self-collected specimens with three methylation markers, that is, CADM1-m18, MAL-m1 and miR-124-2 by quantitative methylation-specific PCR. The areas under the receiver-operating characteristic (ROC) curve for end-point cervical intraepithelial neoplasia grade 3 or worse (CIN3+) were 0.637 for CADM1-m18, 0.767 for MAL-m1 and 0.762 for miR-124-2. This indicates that CADM1-m18 is not suitable as single marker. By varying the thresholds of both markers in the bi-marker panels CADM1-m18/MAL-m1, CADM1-m18/miR-124-2 and MAL-m1/miR-124-2 upper and lower ROC curves were obtained, depicting the maximum and minimum CIN3+ sensitivity, respectively, at given specificity. For all these bi-marker combinations, the upper curves were similar. However, for the MAL-m1/miR-124-2 panel, the distance between upper and lower ROC curves was closest and this panel displayed the highest assay thresholds, indicating that this combination was most robust. At clinical specificities of 50 and 70%, the MAL-m1/miR-124-2 sensitivity for detection of CIN3+ ranged from 77.0 to 87.8% and from 64.9 to 71.6%, respectively. At 70% specificity thresholds no carcinomas were missed. By comparison, the CIN3+ sensitivity of HPV16/18 genotyping on the self-sampled lavage specimens was 58.1% (95%CI: 46.6-68.8) at a specificity of 87.7% (95%CI: 83.2-91.2). In conclusion, methylation analysis is a promising triage tool that in combination with HPV-DNA testing offers feasible, full molecular screening on self-collected cervico-vaginal lavage specimens.

Association between frontal sinus development and persistent metopic suture.

BACKGROUND: Frontal sinuses are 2 irregular cavities, placed between 2 lamina of frontal bone. Expansion continues during childhood and reaches full size after puberty. Persistent metopic suture is one of the factors that are related to abnormal frontal sinus development. In this study, we want to discuss about the coexistence of persistent metopic suture and abnormal frontal sinus development using radiological techniques. MATERIALS AND METHODS: In this retrospectively planned study, images of 631 patients were examined, 217 (34.4%) of them were men and 414 (65.6%) of them were women. Brain computed tomography and magnetic resonance images were retrieved from the electronic archive for analysis. RESULTS: In this study, frontal sinus development is categorised as right side atrophy, left side atrophy, bilateral atrophy and bilaterally developed sinuses. The presence of metopic suture was accepted as persistent metopic suture. Frontal sinus atrophy was found in 22.7% and persistent metopic sutures were found in 9.7% of overall. CONCLUSIONS: In this study, no significant results were detected that were relatedto the frontal sinus agenesis or dismorphism associated with persistent metopicsuture. We conclude that, although publications propounding metopism thatleads to abnormal frontal sinus development are present in the literature, noreasonable explanation has been mentioned in these articles; and we believe thatthese findings are all incidental.

Cytology history preceding cervical cancer diagnosis: a regional analysis of 286 cases.

BACKGROUND: Despite programmed screening in the Netherlands, the decrease in incidence of cervical carcinoma lags behind. We analysed screening results preceding carcinoma cases, timeliness in case of follow-up, and FIGO (International Federation of Gynaecology and Obstetrics) stages as efficiency parameters for screening were taken. METHODS: We analysed 286 women with cervical cancer between 2005 and 2007 for cytology history preceding carcinoma, hierarchically arranging cytology history (if present) into three groups: 'screened', 'work-up', and 'underscreened' (>6 yrs before diagnosis). For screen- and work-up smears, we analysed timeliness. FIGO stage was measured in relation to cytology history. RESULTS: A total of 105 out of 286 (36.7%) women with cervical carcinoma were screened preceding the diagnosis. Delayed time intervals in case of abnormal cytology were 43.5% for borderline/mild dyskaryosis (BMD) and 38.0% for BMD (moderate dyskaryosis or worse; P=0.51). A total of 108 out of 286 (36.4%) women were underscreened, and 73 out of 286 (25.5%) were unscreened. Advanced carcinoma or FIGO stage ≥2B in screened women was 16.0 vs 48.7% in work-up, underscreened, or unscreened (P<0.001). CONCLUSION: Women with cervical cancer are underscreened and have poor timeliness in case of abnormal cytology. Being un- or underscreened correlates significantly with higher cervical cancer stages, especially in older women (aged ≥49 years; P<0.001). Improvement of attendancy is needed to meet the standard of quality for screening programmes.

Modified chitosan-based nanoadjuvants enhance immunogenicity of protein antigens after mucosal vaccination.

Nasal vaccination is considered to be an effective and convenient way of increasing immune responses both systemically and locally. Although various nanovaccine carriers have been introduced as potential immune adjuvants, further improvements are still needed before they can be taken to clinical usage. Chitosan-based nanovaccine carriers are one of the most widely studiedadjuvants, owing to the abilityof chitosan toopen tight junctions between nasal epithelial cells and enhance particle uptake as well as its inherent immune activating role. In present study, bovine serum albumin (BSA) loaded nanoparticles were prepared using novel aminated (aChi) and aminated plus thiolated chitosan (atChi) polymers, to further enhance mucoadhesiveness and adjuvanticity of the vaccine system by improving electrostatic interactions of polymers with negatively charged glycoproteins. Nanocarriers with optimum size and surface charge, high encapsulation efficiency of model antigen and good stability were developed. Negligible toxicity was observed in Calu-3 and A549 cell lines. In vivo studies, revealed high levels of systemic antibodies (IgG, IgG1 and IgG2a) throughout the study and presence of sIgA in vaginal washes showed that common mucosal system was successfully stimulated. Cytokine levels indicated a mixed Th1/Th2 immune response. A shift towards cellular immune responses was observed after nasal immunisation with antigen loaded nanoparticle formulations. These nanoparticles exhibit great potential for nasal application of vaccines.

Nasal vaccination with poly(ß-amino ester)-poly(d,l-lactide-co-glycolide) hybrid nanoparticles.

Mucosal vaccination stimulates both mucosal and systemic immunity. However, mucosal applications of vaccine antigens in their free form generally result in poor systemic immune responses and need adjuvantation. In this study, bovine serum albumin loaded, new hybridised poly(ß-amino ester)-poly(d,l-lactide-co-glycolide) nanoparticles were prepared by double emulsion-solvent evaporation method, characterised and evaluated in vivo as nasal vaccine carriers. Cationic spherical particles with a mean size of 240nm, good physical stability and high encapsulation efficiency were obtained. Protein structure was not affected throughout preparation and minimal toxicity was shown in Calu-3 and A549 cells. Nasal vaccination with these nanoparticles revealed markedly higher humoral immune responses compared with free antigen following intranasal and subcutaneous immunisation. Mucosal immune response was also stimulated and cytokine titres indicated that Th1 and Th2 pathways were successfully activated. This study shows that the formulated hybrid nanoparticles can be a promising carrier for nasal immunisation of poor antigenic proteins.

The effects of the thiolation with thioglycolic acid and l-cysteine on the mucoadhesion properties of the starch-graft-poly(acrylic acid).

The aim of this study is to investigate the effects of the thiolation on the mucoadhesion characteristics of the gelatinized and crosslinked wheat starch-graft-poly(acrylic acid) [(WS-g-PAA)gc] for potential use in drug delivery via vaginal route. Thiolation of (WS-g-PAA)gc was first time realized using l-cysteine hydrochloride monohydrate (CyS) and thioglycolic acid (TGA). These conjugates [(WS-g-PAA)gcth] were characterized using FTIR. The free SH group, mucoadhesion, cytotoxicity characteristics and the mechanism of the thiolation were also evaluated. To obtain fundamental data for possible application such as drug carrier, in vitro and in vivo progesterone release profiles from the mucoadhesive tablet formulations were also determined. The results showed that, vaginal tablet containing (WS-g-PAA)gc-TGA, which has not contain free SH groups in its structure, displays higher mucoadhesion than (WS-g-PAA)gc and (WS-g-PAA)gc-CyS. This tablet formulation can also be used as a drug carrier in vaginal applications.

Non-heart-beating kidney transplantation: 6-year outcomes.

Non-heart-beating donor kidneys (NHBD) are being used to increase the donor pool due to the scarcity of cadaveric heart beating donors (HBD). We evaluated the long-term outcomes of renal transplantation using NHBD kidneys, comparing the first 100 NHBD kidneys transplanted at our facility to the next consecutive cadaveric HBD kidneys for graft survival, recipient survival, and quality of graft function. Recipient survival (P = .22) and graft survival (P = .19) at 6 years did not differ between recipients of NHBD (83%, 80%) and HBD (89%, 87%) kidneys. Quality of graft function using the mean glomular filtration rates were significantly lower in the NHBD group up to 3 months following discharge (41 +/- 2 vs 47 +/- 2, P = .007) but were then comparable up to 6 years following transplantation (43 +/- 5 vs 46 +/- 4, P = .55).

Lab-on-a-chip based biosensor for the real-time detection of aflatoxin.

Polymers were synthesized and utilized for aflatoxin detection coupled with a novel lab-on-a-chip biosensor: MiSens and high performance liquid chromatography (HPLC). Non-imprinted polymers (NIPs) were preferred to be designed and used due to the toxic nature of aflatoxin template and also to avoid difficult clean-up protocols. Towards an innovative miniaturized automated system, a novel biochip has been designed that consists of 6 working electrodes (1mm diameter) with shared reference and counter electrodes. The aflatoxin detection has been achieved by a competition immunoassay that has been performed using the new biochips and the automated MiSens electrochemical biosensor device. For the assay, aflatoxin antibody has been captured on the Protein A immobilized electrode. Subsequently the sample and the enzyme-aflatoxin conjugate mixture has been injected to the electrode surfaces. The final injection of the enzyme substrate results in an amperometric signal. The sensor assays for aflatoxin B1 (AFB1) in different matrices were also performed using enzyme link immunosorbent assay (ELISA) and HPLC for confirmation. High recovery was successfully achieved in spiked wheat samples using NIP coupled HPLC and NIP coupled MiSens biosensor [2ppb of aflatoxin was determined as 1.86ppb (93% recovery), 1.73ppb (86.5% recovery), 1.96ppb (98% recovery) and 1.88ppb (94.0% recovery) for immunoaffinity column (IAC)-HPLC, NIP-HPLC, Supel™ Tox SPE Cartridges (SUP)-HPLC and NIP-MiSens, respectively]. Aflatoxin detection in fig samples were also investigated with MiSens biosensor and the results were compared with HPLC method. The new biosensor allows real-time and on-site detection of AFB1 in foods with a rapid, sensitive, fully automated and miniaturized system and expected to have an immense economic impact for food industry.

The short- and long-term effectiveness of transcatheter arterial embolization in patients with intractable hematuria.

PURPOSE: Selective transarterial embolization (TAE) of the internal iliac artery is a well-known alternative technique to control intractable bladder hemorrhage (IBH). We explored the short- and long-term effectiveness of, and clinical outcomes after, TAE in patients with IBH. MATERIALS AND METHODS: In this retrospective study, we reviewed the hospital records of 18 IBH patients non-responsive to conservative medications who underwent TAE between January 2003 and May 2014. The early- and long-term effectiveness of TAE was investigated in the context of hematuria control, complications, mortality, requirement for blood transfusions, and hematocrit level. RESULTS: Sixteen of the 18 patients underwent endovascular treatment; the technical success rate was 88%. TAE allowed complete remission in 16 patients (100% clinical success). On follow-up, mean hematocrit (P=0.003) and hemoglobin (P=0.005) levels significantly improved. Thirteen of the 16 patients (81%) required no further emergency admission after TAE during a mean follow-up period of 18.1months (range, 3-105months). CONCLUSION: TAE is a feasible, effective, and safe technique in both the short- and long-term for the treatment of IBH.

Evaluation of daclizumab to reduce delayed graft function in non-heart-beating renal transplantation: a prospective, randomized trial.

Daclizumab (DZB), an interleukin-2 receptor blocker, has been shown to reduce the rate of acute rejection, while non-heart-beating kidney recipients have high rates of delayed graft function that may be prolonged by high levels of calcineurin inhibitors. This study assessed whether DZB could safely replace calcineurin inhibitors in the immediate postoperative period and promote recovery from ischemic acute tubular necrosis. Patients were randomized into one of two groups: DZB induction and daily mycophenolate mofetil (MMF; 2 g) with steroids (20 mg prednisone) or standard triple therapy with tacrolimus, MMF, and prednisone. Patients in the DZB arm were converted to the control arm when either the serum creatinine dropped to <350 micromol/L or there was biopsy evidence of acute rejection. Over 2 years, Leicester and Newcastle non-heart-beating donor (NHBD) centers recruited 51 patients. There was one patient death in the DZB arm, during the study period, after a nonfunctioning graft was removed. A total of two (8%) grafts in the DZB arm and three (11.5%) grafts in the control arm failed to function. The overall rate of immediate function improved from around 5% (pre-2001) to 28%. There were no significant differences in the incidence of acute rejection or graft function (GFR) at 3 months. Machine-perfused kidneys in DZB-treated recipients had the highest rates of immediate function (53%, P = .015). We found that a calcineurin-sparing regime is safe and may be beneficial for recipients of machine-perfused grafts damaged by warm ischemia.

A simple cardiovascular risk score can predict poor outcome in non-heart-beating donor renal transplantation.

A simple cardiovascular risk score used in our centre to plan cardiovascular work-up for renal transplantation can predict outcome in non-heart-beating donor (NHBD) renal transplantation. Patients in the higher-risk group, with a score of >12 of a maximum of 36 are likely to have a longer duration of delayed graft function, poorer glomerular filtration rate at 6 months, and inferior graft and patient survival, together with a relative rate of graft loss within 60 days of 4.514 (P = .019) and within 1 year of 3.511 (P = .036). Although a high cardiovascular risk score should not be regarded as a contraindication to NHBD transplantation, the score can be used to facilitate recipient selection.

Factors predicting duration of delayed graft function in non-heart-beating donor kidney transplantation.

Non-heart-beating donors (NHBDs) are an important potential source of donor organs, but kidneys from such donors are prone to delayed graft function (DGF) and primary nonfunction, which are multifactorial in origin but believed to be mainly due to warm ischemic injury. This retrospective study examined a series of 88 transplants from Maastricht category II and III NHBDs to examine the role of factors to predict the duration of DGF. The main factors affecting duration of DGF were total warm ischemic time, cold ischemic time, product of perfusate GST concentration and donor age, quality of postoperative graft perfusion, incidence of acute rejection, recipient cardiovascular risk score, maximum pressure on machine perfusion, and weight gain during machine perfusion. Primary nonfunction was not accurately predicted from these factors for kidneys that had passed the viability assessment.

Anti-vimentin antibody detection in recipients of heart-beating and non-heart beating donor kidneys.

Alternative donor sources include non-heart-beating donors (NHBDs). There donors have been exposed to significant ischemia, so that it is common to utilize machine perfusion to either improve the organs or at least assess their viability. Both prolonged warm ischemia and machine perfusion can potentially damage the vascular endothelium, thereby exposing vimentin to antigenic recognition. The aim of this study was to determine whether anti-vimentin antibodies could be detected in the blood of renal transplant recipients at specific time points after transplant and whether they could be related to the donor source. Fifty-one recipients of NHBD kidneys were compared to 52 recipients of heart-beating donor (HBD) kidneys. All recipients had similar anti-vimentin levels pretransplant. However, at 1 month those kidneys from Maastricht category II NHB donors showed significantly higher levels. At 6 months both Maastricht category II and category III NHB donor recipients displayed significantly higher levels than recipients of HBD kidneys.

Cardiovascular risk assessment scoring system for the determination of cardiovascular mortality in renal transplant patients.

It is well known that the greatest risk for mortality post-renal transplant is cardiovascular death. We compared a modified cardiac risk assessment system among renal transplant patients who subsequently died versus the group that survived. There was a good correlation between the low, medium, and high scores with survival. The deceased group had significantly greater cardiovascular scores than case controls.

Variation in organ donation in northeastern England 1986 to 2003.

Renal transplantation is established as the best form of renal replacement therapy, but demand for kidneys exceeds supply from cadaveric donations. It is therefore important to make the best use of the pool of potential cadaveric organ donors. Donation rates are to a large extent dependent on public opinions, which may be influenced by external events. In northeast England from 1986 to 2003, there was a potential pool of 1170 brain stem-dead donors, of whom 190 (16%) could not be retrieved due to relatives' objections. From 1998 to 2003 we were referred 90 potential non-heart-beating donors, of whom relatives refused donation in 10 (11%). A major reason for not retrieving organs from a potential donor has been lack of consent from the relatives. Refusals appear to vary year by year and are consistently lower for non-heart-beating donors. This therefore raises the possibility that negative or positive media publicity plays a role in this variation.