Magnesium yields opposite effects on the nuclear and cytosolic cascades of apoptosis in different rat brain regions.

OBJECTIVE: Magnesium is considered as potential neuroprotective and therapeutic agent, but certain studies have provided evidence of its apoptotic effectiveness in neurons. We aimed to evaluate the possible apoptotic effects of long-term magnesium use in healthy adult rat brains. MATERIALS AND METHODS: Magnesium citrate and magnesium glycinate compounds were administered orally to rats for 8 weeks (36 mg/kg). Expression levels of Bcl-2, Bax and Cyt-C genes were analyzed by real-time polymerase chain reactions (RT-PCR) in the prefrontal cortex, hippocampus and striatum regions. Bcl-2, Bax and CytC protein levels were measured using ELISA kits. Tissue sections were evaluated histopathologically with hematoxylin-eosin staining. RESULTS: Compared to the control group, the magnesium-administered groups indicated gene expression reductions in almost all brain regions; pro-apoptotic Bax, anti-apoptotic Bcl-2 and Cyt-C gene expression levels were reduced. With magnesium, the Bcl-2 and Bax protein levels were increased. Bax/Bcl-2 gene and protein ratio were also increased in the striatum and hippocampus, whereas Cyt-C protein levels were decreased or did not change in the magnesium treated groups. There was no pathological finding in histological evaluation. CONCLUSIONS: Long-term magnesium usage can promote apoptotic cascade in brain tissue by increasing Bax/Bcl-2 ratio. Cyt-C, a prominent factor processing caspase pathway, was decreased or unchanged. In addition, taking into account the histological evaluation, we supposed that the absence of Cyt-C in the cytosol can prevent the subsequent apoptotic pathway. Consequently, we obtained the findings of apoptotic initiation with magnesium in brain, but this cascade seems to be arrested at later stages.

Molecular evidence for concurrent infection of goats by orf virus and bovine herpesvirus 1.

Orf is a disease of small ruminant animals, including goats and sheep, that is caused by a parapoxvirus. Although the mortality rate is low, economic losses may occur due to the clinical signs. Bovine herpesvirus 1 (BoHV-1) infection is known to cause respiratory and reproductive disorders mainly in cattle; however, it has been found to circulate among goats and sheep as well. In contrast to orf virus (ORFV), BoHV-1 does not induce clinical disease in goats. In this study, we aimed to detect the presence of ORFV by molecular methods and to uncover eventual simultaneous herpesvirus infections masked by orf disease signs. To this end, 82 goats, housed near to a cattle herd, were tested. By polymerase chain reaction (PCR), three goats (3.7%) were found to harbour both viruses, while an additional goat was positive for ORFV only. The PCR products were sequenced and phylogenetic analyses were performed. This study revealed that ORFV and BoHV-1 may be present simultaneously in an animal causing a concurrent infection. These data should be taken into consideration when looking for secondary pathogens in diseased goats, and the prevention methods should be developed accordingly.

New αIIbß3 variants in 28 Turkish Glanzmann patients; structural hypothesis for complex activation by residues variations in I-EGF domains.

Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder characterized by impaired platelet aggregation due to defects in integrin αIIbß3, a fibrinogen receptor. Platelet phenotypes and allelic variations in 28 Turkish GT patients are reported. Platelets αIIbß3 expression was evaluated by flow cytometry. Sequence analyzes of ITGA2B and ITGB3 genes allowed identifying nine variants. Non-sense variation effect on αIIbß3 expression was studied by using transfected cell lines. 3D molecular dynamics (MDs) simulations allowed characterizing structural alterations. Five new alleles were described. αIIb:p.Gly423Asp, p.Asp560Ala and p.Tyr784Cys substitutions impaired αIIbß3 expression. The αIIb:p.Gly128Val substitution allowed normal expression; however, the corresponding NM_000419.3:c.476G>T variation would create a cryptic donor splicing site altering mRNA processing. The ß3:p.Gly540Asp substitution allowed αIIbß3 expression in HEK-293 cells but induced its constitutive activation likely by impairing αIIb and ß3 legs interaction. The substitution alters the ß3 I-EGF-3 domain flexibility as shown by MDs simulations. GT variations are mostly unique although the NM_000419.3:c.1752 + 2 T > C and NM_000212.2:c.1697 G > A variations identified in 4 and 8 families, respectively, might be a current cause of GT in Turkey. MD simulations suggested how some subtle structural variations in the ß3 I-EGF domains might induce constitutive activation of αIIbß3 without altering the global domain structure.

Antibacterial and Cellular Behaviors of Novel Zinc-Doped Hydroxyapatite/Graphene Nanocomposite for Bone Tissue Engineering.

Bacteria are one of the significant causes of infection in the body after scaffold implantation. Effective use of nanotechnology to overcome this problem is an exciting and practical solution. Nanoparticles can cause bacterial degradation by the electrostatic interaction with receptors and cell walls. Simultaneously, the incorporation of antibacterial materials such as zinc and graphene in nanoparticles can further enhance bacterial degradation. In the present study, zinc-doped hydroxyapatite/graphene was synthesized and characterized as a nanocomposite material possessing both antibacterial and bioactive properties for bone tissue engineering. After synthesizing the zinc-doped hydroxyapatite nanoparticles using a mechanochemical process, they were composited with reduced graphene oxide. The nanoparticles and nanocomposite samples were extensively investigated by transmission electron microscopy, X-ray diffraction, and Raman spectroscopy. Their antibacterial behaviors against Escherichia coli and Staphylococcus aureus were studied. The antibacterial properties of hydroxyapatite nanoparticles were found to be improved more than 2.7 and 3.4 times after zinc doping and further compositing with graphene, respectively. In vitro cell assessment was investigated by a cell viability test and alkaline phosphatase activity using mesenchymal stem cells, and the results showed that hydroxyapatite nanoparticles in the culture medium, in addition to non-toxicity, led to enhanced proliferation of bone marrow stem cells. Furthermore, zinc doping in combination with graphene significantly increased alkaline phosphatase activity and proliferation of mesenchymal stem cells. The antibacterial activity along with cell biocompatibility/bioactivity of zinc-doped hydroxyapatite/graphene nanocomposite are the highly desirable and suitable biological properties for bone tissue engineering successfully achieved in this work.

New members to Arctic-like lineage of canine distemper virus from Turkey.

Canine distemper virus (CDV) causes a multisystemic fatal disease, briefly named as distemper, in domestic and wild animals. Molecular characterization studies serve to identify local strains, accordingly, helps to determine the scope of vaccination in prevention of distemper. We aimed with this study to update the molecular status of CDV in domestic dogs in Turkey. Sequence analysis of the H gene revealed that novel Turkish sequences formed a separated clade in Arctic-like lineage. Italian clade which mainly included strains originated from wild canid or non-canid localized nearly to novel Turkish clade. Codons 530th and 549th determining the affinity of domestic or wild animals to distemper were Asparagine and Tyrosine, respectively. This report presented the presence of CDV strains belonging to Arctic-like lineage for the first time in domestic dogs in Turkey. The findings pave the way for the reassessment of the circulation and geographical shifting of Arctic-like lineages of CDV.

A phylogenetic study of Feline Immunodeficiency Virus (FIV) among domestic cats in Turkey.

Feline Immunodeficiency Virus (FIV) is the most prominent retrovirus in cats. Molecular studies on FIV are of great importance to enable further studies, for example, understanding the pathogenesis and developing improved vaccines. We aimed to elucidate the molecular status of FIV and provide a detailed characterization of FIV in Turkey because at present there is very limited information available in the literature. We also evaluated a potential link between clinical symptoms and FIV subtypes according to results obtained from molecular tests. Whole blood was collected from 200 client-owned domestic cats and molecular diagnosis and characterization was performed. The env, gag and vif gene regions were amplified and sequenced for phylogenetic analysis. We obtained specific amplicons based on bothenvand gag for FIV in 21 cats; only 2 of the 21 positive samples could also be characterized based on the vif gene region. Separate clusters were identified according to previously determined genotyping strategies; however, they were observed in FIV subtype B. The molecular findings of some individual cats were evaluated in conjunction with their clinical symptoms in an attempt to determine potential relationships between the genetic characteristics of FIV and symptoms of disease. As a result, overexpression of the vif gene could be important in leading to serious clinical symptoms. Our results emphasize the necessity of considering FIV in diagnosis and performing the neccesary diagnostics to confirm or rule out FIV infection. The molecular dynamics of FIV should be periodically updated by further analyses to establish a successful prevention strategy.

A serological investigation of Bovine enterovirus-1, Bovine herpesvirus-1, Bovine viral diarrhea virus, and Parainfluenza-3 infections in camelsin Western Turkey.

Camels (Camelus dromedarius) are bred in Western Turkey, particularly in the province of Aydin, for touristic, social and cultural purposes. Bovine enterovirus­1 (BEV­1), Bovine herpesvirus type­1 (BHV­1), Bovine viral diarrhea virus (BVDV), and Parainfluenza­3 (PI­3) virus infections are significant causes of health and/or economic concerns in several animal species. These agents have not been investigated in the camel population in Turkey. The objective of this study was to serologically investigate the presence and infection rates of these viruses in camels in Aydin province, Western Turkey. Ninety­two serum samples were taken from clinically healthy camels that were kept in private farms or brought to the local slaughterhouses. Serum neutralization test was performed to assess the presence and the titers of specific antibodies against BEV­1, BHV­1, BVDV, and PI­3 virus in camel sera. Of the 92 camels tested, 30 (32.61%), 2 (2.17%), 54 (58.7%), and 20 (21.74%) were seropositive for BEV­1, BHV­1, BVDV, and PI­3, respectively. These results suggest that, except for BHV­1, these viral infections are common among camels in Western Turkey. To our knowledge, this the first comprehensive, large­scale study investigating these viral infections in camels in Turkey.

First report on the prevalence and genetic relatedness of Feline Foamy Virus (FFV) from Turkish domestic cats.

Feline Foamy Virus (FFV) is an important retroviral agent affecting domestic cats in Turkey that has been studied less intensively than Feline Immunodeficiency Virus (FIV) and Feline Leukemia Virus (FeLV). Accordingly, we aimed to investigate the presence and prevalence of FFV among domestic cats by molecular techniques. PCR was used to amplify the gag-pol gene overlap in order to detect the presence of FFV. The gene encoding bet, an important accessory gene, was also characterized. Molecular characteristics were analyzed and phylogenetic trees were constructed. We determined the positivity rate as 10% in all samples (20/200) based on the gag-pol test. The phylogenetic analysis indicated that the Turkish FFV sequences form a separate cluster among other isolates in the constructed maximum likelihood (ML) tree. bet-based products were obtained for two samples (1%; 2/200) that were also positive for gag-pol. These bet gene sequences confirm the presence of a separate cluster for the Turkish FFV isolates. The results suggest that FFV is prevalent and widespread in Turkish domestic cats. Additionally, these new FFV sequences represent the first FFV sequences from Turkey to be submitted to GenBank. This study paves the way for studies on the pathogenicity of FFV.

Short-term pain reduction after low-dose radiotherapy in patients with severe osteoarthritis of the hip or knee joint: a cohort study and literature review.

BACKGROUND: Low-dose radiotherapy (LDRT) for pain reduction in osteoarthritis (OA) is a frequently used treatment in Germany and Eastern European countries. The evidence on the effects of LDRT on pain in patients with OA remains unclear. This study evaluated the effect of LDRT on pain in patients with severe OA of the hip or knee joint. METHODS: This prospective study included a total of 16 joints in 12 patients (4 hips and 12 knees). The inclusion criteria were: patients older than 50 years, severe OA (Kellgren-Lawrence grade III-IV) of the hip or knee joint, patients not responding to conservative treatment and patients who are inoperable or not willing to undergo surgery. The joint was irradiated with a total dose of 6.0 Gray. The Numeric Rating Scale for pain (NRS-pain) and patient-reported outcome measures were obtained at pre-, 6, 13, 26, 39 and 52 weeks post-radiation. A decrease of two points on the NRS-pain was defined as clinical relevant. RESULTS: The median age of the included patients was 74 years (range 58-89). In 50% of the joints (n = 8, 3 hip and 5 knee joints), a clinical relevant difference in pain at 6 weeks post-radiation was observed. This clinical relevant difference decreased to 25% at 52 weeks post-radiation. CONCLUSION: LDRT showed a clinical relevant pain relief at 6 weeks after radiotherapy. The long-term effect of LDRT, however, was limited. A randomized placebo-controlled trial is necessary to assess the effect of LDRT on pain in patients with OA of the hip or knee joint.

[A soccer player with an unstable knee]. / Een voetballer met een instabiele knie.

A 19-year-old soccer player presented with instability of his left knee after a rotation trauma. Congenital absence of the anterior cruciate ligament was suspected because of leg length discrepancy and specific MRI findings. He regained stability after an anterior cruciate reconstruction.

Cell sheet based bioink for 3D bioprinting applications.

In this research, a novel development of bioink from cell sheets is presented for scaffold free bioprinting applications. Poly(N-isopropylacrylamide) (PNIPAAm) coated surfaces were first prepared by using initiated chemical vapor deposition method. Cell-sheets were then grown on these thermoresponsive pNIPAAm coated surfaces and easily detached without disturbing delicate cell-extracellular matrix (ECM) and cell-cell interactions. The detached cells sheets were used to prepare cell sheet based bioink and bioprinted to form various shapes. The results showed that the prepared cell-sheet based bioink shows an increase in the structural integrity compare to cell-aggregates suggesting that the cell sheet aggregates preserved interconnected ECM proteins. The viability of cell sheet based aggregates was also compared to single cell aggregates at three different time points in a seven-day period after printing. The developed cell-sheet based bioink has several advantages in terms of shape fidelity, reproducibility and automated deposition for bioprinting applications. The results also demonstrated that the bioprinted constructs secreted collagen type I which is a strong indication of starting ECM deposition. Moreover, the immunostaining results showed that the fibronectin in cell sheets was preserved during and after the preparation process of bioink.

Effectiveness of a Multidisciplinary Clinical Pathway for Elderly Patients With Hip Fracture: A Multicenter Comparative Cohort Study.

INTRODUCTION: The use of a multidisciplinary clinical pathway (MCP) for patients with hip fracture tends to be more effective than usual care (UC). The aim of this study was to evaluate the effects of an MCP approach on time to surgery, length of stay, postoperative complications, and 30-day mortality, compared to UC. MATERIALS AND METHODS: This multicenter retrospective cohort study included patients aged 50 years or older with a proximal hip fracture who underwent surgery in one of the 6 hospitals in the Limburg trauma region of the Netherlands in 2012. Data such as demographics, process outcome measures, and clinical outcome were collected. RESULTS: This study included a total of 1193 patients (665 and 528 patients in the MCP and UC groups, respectively). There were no differences in patient demographics present. Time to surgery was significantly shorter in the MCP compared to the UC group (19.2 vs 24.4 hours, P < .01). The mean length of stay was 10 versus 12 days (P < .01). In the MCP group, significantly lower rates of postoperative complications were observed and significantly more patients were institutionalized than in the UC group. Mortality within 30 days after admission was comparable between the groups (overall mortality 6%). CONCLUSION: An MCP approach is associated with reduced time to surgery, postoperative complications, and length of stay, without a significant difference in 30-day mortality. The institutionalization rate was significantly higher in the MCP group.

Benefits of radial head excision in patients with haemophilia: mid-term functional results.

INTRODUCTION: Recurrent haemarthrosis in haemophilic patients result with arthropathy of the radiocapitellar joint and blockage of the forearm rotation. AIM: The aim of this study is to evaluate the mid-term results of radial head excision with partial synovectomy in severe haemophilic patients retrospectively. METHODS: Persistent pain and decreased forearm rotation were the main indications for radial head excision. Between 2002 and 2013, radial head excisions were performed for 14 elbows of 14 patients. Eleven patients were haemophilia A, whereas two patients were haemophilia B patients and the remaining one had von Willebrand (Type 3) disease. The mean age of the patients was 29 at the time of the surgery. The mean follow-up was 51 (12-155) months. VAS (visual analogue score) for pain, forearm rotation, qDASH and MEPS (Mayo Elbow Performance Score) were used as the primary outcome parameters. RESULTS: The mean VAS decreased significantly from 6.5 preoperatively to 2.2 at the final follow-up (P = 0.0003). The mean forearm rotation increased from 40° to 115° respectively (P = 0.0007). In two patients, efficacious rotation increase was not achieved due to distal radioulnar joint problems. The mean qDASH score and MEPS were 18.1 and 87.5 at the latest follow-up, respectively, where four patients had excellent and 10 patients had good results. CONCLUSIONS: Radial head excision is a safe and effective procedure for haemophiliac patients with radiocapitellar arthropathy and decreased forearm rotation. Distal radioulnar joint should be evaluated preoperatively which may impair the results.

First molecular detection and characterization of Akabane virus in small ruminants in Turkey.

Abortion outbreaks associated with congenital malformations in two distinct small-ruminant flocks were reported in Turkey in 2013-2014. This paper describes the first molecular characterization of Turkish Akabane virus strains in small-ruminant flocks using partial sequence analysis of the S segment and pathological findings.

Incidental thyroid lesions on FDG-PET/CT: a prevalence study and proposition of management.

AIM: Thyroid incidentaloma is defined as an unsuspected, asymptomatic thyroid lesion that is discovered on an imaging study. The purpose of this study is to determine incidentally identified thyroid lesions by FDG-PET/CT in cancer patients by virtue of preoperative staging and to pay attention how should be the management of these patients with thyroid lesion. METHODS: From January 2011 to January 2013, 2654 patients underwent FDG-PET/CT in our institution. Among them, 34 patients had thyroid incidentaloma. All patients underwent ultrasonographic (US) examination. If there is a nodul, fine needle aspirations (FNA) were performed to these patients. We did not perform FNA to patients who had diffuse thyroid uptake. Patients were divided into two groups; malign and non-malign patients according to FNA histo-pathologic results. Group 1 (N.=11) diagnosed malignancy in histo-pathologic evaluation, group 2 (N.=23) could not diagnosed malignancy in histo-pathologic, clinic and radiologic evaluation. These two groups were compared statistically in terms of SUV max levels that reached in PET examinations. RESULTS: Incidentally thyroid lesions were found in 34 patients in the course of FDG-PET/CT examination (25 females and 9 males), mean age 57.7 years. Nodular goitre in 12 patients, hyperthyroidism in 2 patients, sub-clinic hyperthyroidism in 3 patients and hashimoto thyroiditis in 6 patients were diagnosed in non-malignancy group (Group-2). Group 1 included 11 patients with incidentally diagnosed thyroid malignancy. 11 patients malignancy diagnoses were verified by FNA and 9 of them were operated. In PET evaluation thyroid up-take was diffuse in 9 patients, at left lob in 12 patients and at right lop in 13 patients. When we compared the groups according to SUV max levels; we found that malignant thyroid lesions had a significantly higher (P<0.001) SUVmax than benign thyroid lesions. A cut off SUVmax value (>6.2) was found in the study. CONCLUSION: The incidental finding of focal thyroid uptake on FDG-PET scanning has an elevated malignancy risk from other thyroid nodules. According to our knowledge diagnose, treatment and follow-up of these patients should be in multidiscipliner approach. Oncology, endocrinology, endocrine surgeon, interventional radiology, pathology and psychiatry should be gathered in multidiscipliner team. For these reason these patients need more careful evaluation.

A Report on Bovine Ephemeral Fever Virus in Turkey: Antigenic Variations of Different Strains of EFV in the 1985 and 2012 Outbreaks Using Partial Glycoprotein Gene Sequences.

We described the aetiological agents of outbreaks of bovine ephemeral fever (BEF) that occurred in 1985 and 2012 in Turkey, and identify mutations in the viruses from both outbreaks. Outbreaks have emerged periodically every 4-5 years in the same regions in Turkey. Because these regions are located in a subtropical climatic zone, good conditions for vector populations exist. The results of this study show that the BEFVs from outbreaks in Turkey vary significantly. Effective prevention will require a vaccine that contains BEFVs from different genetic clusters.

Unpredictable behavior of breast phyllodes tumors.

OBJECTIVE: Phyllodes Tumor is a rare fibroepithelial breast tumor with variable malignant potential. These tumors that currently accepted nomenclature are benign, borderline and malignant according to the World Health Organization. It tends to behave in a benign way but it may undergo a malignant transformation. The purpose of this study was to present our Case load of phyllodes tumor, and evaluate the management and follow-up the behavior of these tumors. PATIENTS AND METHODS: 36 patients with phyllodes tumor were treated in Bezmialem Vakif University and Okmeydani Training and Research Hospitals analyzed retrospectively. Demographics, presenting symptoms, history, local examination, preoperative clinical diagnosis, treatment, postoperative histopatology, follow-up period were evaluated retrospectively and studied. RESULTS: A total of 36 patients treated for phyllodes tumor were analyzed. Mean age of the patients was 38 (14-79) and all were females. The presentation of the patients was breast lump in all cases, either as a primary or recurrent lump presentation. The right and left breast were affected 58% and 42% respectively. 34 of these 36 cases are briefly mentioned in this paper but the two cases, one with sarcomatous malignant transformation and the other with fatal metastatic phyllodes tumor in an adolescent female are discussed in detail. The mean duration of the symptomatic mass was 9.8 ± 7.3 months (range 0.5 to 24). CONCLUSIONS: Phyllodes tumor is a type of tumor that may be benign or malignant. The type with malignant features may be fatal. The tumors diagnosed as benign may transform and become malignant because of unknown reasons and may be an aggressive tumor.

LigaSure® versus clamp tie technique for thyroid surgery; decreased operative time versus increased inflammatory effect: a prospective randomized study.

OBJECTIVE: The aim of this study was to compare the LigaSure® Small Jaw Instrument (LSJI) with the conventional clamp-and-tie (CT) technique in thyroid surgery regarding complication rates (hematoma, hypocalcemia and recurrent nerve palsy), the duration of the operative procedure, and systemic and local inflammatory effects. PATIENTS AND METHODS: Fifty-four consecutive patients were randomized prospectively into two groups, a Conventional Clamp-Tie (CT) group and a LigaSure® Vessel Sealing System (LVSS) Group. Pre- and postoperative blood plasma samples were taken to measure the tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), calcium, parathormon, CRP levels and WBC, as well as the lymphocyte subset (CD3, CD4, CD8, CD16/56, CD19) counts. The drain fluid samples were collected after the removal of the drains to measure the levels of IL-6 and TNF-α. RESULTS: Both groups showed significant changes regarding peripheral blood CD3+, CD4+, and CD8+ T cell levels (p < 0.05). In the LVSS group, the level of CD16+56+ NK cells showed a significant decrease compared with the CT group (p < 0.05). The IL-6 and TNF-α levels in the drainage fluid were significantly higher in the LVSS group. CONCLUSIONS: We demonstrated that LSJI can decrease operative time. Although the systemic inflammatory effect of LSJI remains inconclusive, the local inflammatory effect was significant, which could cause early and late postoperative problems.

Is Hashimoto's thyroiditis a prognostic factor for thyroid papillary microcarcinoma?

AIM: The relationship between papillary thyroid carcinoma (PTC) and accompanying Hashimoto's thyroiditis (HT) has been investigated extensively. However, there is no agreement among the authors. We aimed with this study to investigate this relationship in a limited subtype of PTC called papillary thyroid microcarcinoma (PTMC). PATIENTS AND METHODS: Between January 1999 and December 2012, 1923 thyroids were surgically resected in two referral centers and thoroughly inspected for evidence of PTMC. Of these patients, 172 who were diagnosed with PTMC had demographic and pathological features recorded. RESULTS: Fourteen patients (8.1%) were found to have CLN metastases. Eleven (78.6%) of the patients with CLN metastases had tumors larger than 5 mm, and 3 (21.4%) patients with CLN metastases had small tumors (≤ 5 mm), but there was no statistical significance (p > 0.05). Accompanying Hashimoto's thyroiditis (HT) was detected in 67 (39%) patients. The CLN metastasis rate was slightly higher in cases with HT in surrounding thyroid tissue. However, there was no statistical significance; the CLN rate was 6.7% (n=7) in patients without thyroiditis and 10.4% (n=7) with Hashimoto's thyroiditis. Insufficient FNA results in patients with thyroiditis were associated with HT (p < 0.05). CONCLUSIONS: Surgeons and other clinicians who play a role in the treatment of thyroid cancers should be aware that some PTMC cases may show a worse course, as with some PTCs, contrary to expectations.