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In orthopedic surgery, metals are preferred to support or treat damaged bones due to their high mechanical strength. However, the necessity for a second surgery for implant removal after healing creates problems. Therefore, biodegradable metals, especially magnesium (Mg), gained importance, although their extreme susceptibility to galvanic corrosion limits their applications. The focus of this study was to control the corrosion of Mg and enhance its biocompatibility. For this purpose, surfaces of magnesium-calcium (MgCa1) alloys were modified with calcium phosphate (CaP) or CaP doped with zinc (Zn) or gallium (Ga) via MgCa1 microarc oxidation. The effects of surface modifications on physical, chemical, and mechanical properties and corrosion resistance of the alloys were studied using surface profilometry, goniometry, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), nanoindentation, and electrochemical impedance spectroscopy (EIS). The coating thickness was about 5-8 mu m, with grain sizes of 43.1 nm for CaP coating and 28.2 and 58.1 nm for Zn- and Ga-doped coatings, respectively. According to EIS measurements, the capacitive response (Y-c) decreased from 11.29 to 8.72 and 0.15 Omega(-1) cm(-2) s(n) upon doping with Zn and Ga, respectively. The E-corr value, which was -1933 mV for CaP-coated samples, was found significantly electropositive at -275 mV for Ga-doped ones. All samples were cytocompatible according to indirect tests. In vitro culture with Saos-2 cells led to changes in the surface compositions of the alloys. The numbers of cells attached to the Zn-doped (2.6 x 10(4) cells/cm(2)) and Ga-doped (6.3 x 10(4) cells/cm(2)) coatings were higher than that on the surface of the undoped coating (1.0 x 10(3) cells/cm(2)). Decreased corrosivity and enhanced cell affinity of the modified MgCa alloys (CaP coated and Zn and Ga doped, with Ga-doped ones having the greatest positive effect) make them novel and promising candidates as biodegradable metallic implant materials for the treatment of bone damages and other orthopedic applications.

Aim: In this study, we aimed to analyze the effect of prognostic nutritional index and neutrophile lymphocyte ratio on the overall survival (OS) in patients treated with regorafenib. Materials and Methods: Metastatic colorectal cancer (CRC) patients who treated with regorafenib between 2016 and 2020 in a single center were evaluated retrospectively. ROC analysis was used for neutrophile lymphocyte ratio (NLR’s) and prognostic nutritional index (PNI’s) optimum cut‑off value. The relationship between OS with PNI and NLR was investigated. Results: Fifty‑two patient’s data were analyzed. The median age was 57 years, 22 (41.5%) of the patients were female. The optimal cut‑off value of PNI for OS was 45.7 according to ROC curve analysis. The median NLR value was accepted as 2.7. Median OS was 8.3 months. Patients who have high PNI value than 45.7 had longer OS (12.09 months vs. 6.31 months hazard ratio [HR]: 0.37 95% confidence interval [CI]: 0.19–0.73 P = 0.003) and there was a tendency for longer OS with low NLR value then median (12.05 months vs. 6.14 months HR: 0.54 95% CI: 0.29–1.23 P = 0.057). Primary tumor resected patients had longer OS than nonresected patients (12.05 months vs. 6.30 months HR: 0.34 95% CI: 0.17–0.66 P = 0.001). In multivariate analysis, high PNI value more than 45.7 (HR: 0.40 95% CI: 0.18–0.88 P = 0.02) and resection of the primary tumor (HR: 0.40 95% CI: 0.21–0.80 P = 0.01) were the only independent factors for longer OS. Conclusion: Metastatic CRC patients with high pretreatment PNI and primary tumor resected are more likely to have longer OS with regorafenib. PNI is more reliable index than NLR to predict OS in metastatic CRC patients treated with regorafenib.

The parathyroid glands are localized at the back of the thyroid glands in the cervical region and are responsible for regulation of the calcium level in the blood, through specialized cells that sense Ca2+ and secrete parathyroid hormone (PTH) in response to a decline in its serum level. PTH stimulates the skeleton, kidneys and intestines and controls the level of Ca2+ through specialized activities. Iatrogenic removal of the parathyroid gland, as well as damage to its vascular integrity during cauterization are some of the common complications of thyroid surgery. Therefore, regeneration and/or replacement of malfunctioning parathyroid tissue is required. Tissue engineering is an emerging and promising field for patients with organ failure with recent pioneering clinical applications. The success of tissue engineering strategy depends on the use of proper cells, bioactive factors that stimulate the activities of these cells and scaffolds that are produced to recapitulate the tissue structure and support the function of the engineered tissues. 3D printing is a developing strategy for the production of these scaffolds by providing a delicate control over their structure and properties. In this study, human primary parathyroid cells were successfully isolated and their viability and ability to secrete PTH upon stimulation with different levels of Ca2+ were shown in vitro. These cells were then seeded onto 3D printed alginate scaffolds and 3D bioprinted within alginate bioink, and cell viability as well as the ability to secrete PTH upon stimulation were also demonstrated. Therefore, functional hormone-active parathyroid tissue substitute was engineered in vitro through 3D printed hydrogels and autologous cells.

To demonstrate whether early changes in systemic inflammatory markers are related with pazopanib treatment response in soft tissue sarcoma and renal cell carcinoma.Forty-one patients with metastatic clear cell renal carcinoma (mRCC) (n=22) and advanced stage soft tissue sarcoma (STS) (n=19) were assessed. Systemic inflammatory markers such as neutrophils, lymphocytes, c-reactive protein (CRP), mean platelet volume (MPV), lactate dehydrogenase (LDH) and neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) at both baseline and 1-month of pazopanib treatment were obtained and their relation with the first radiological response about 3-months later after pazopanib treatment was evaluated.Disease control rate (DCR) at the first initial radiological evaluation was 58.5 % for all, it was 77.3% for the RCC group and 36.8% in the STS group. Serum neutrophil, NLR and CRP levels were significantly decreased from baseline in RCC patients who had DCR with pazopanib treatment. Also, serum CRP levels after pazopanib treatment was significantly lower in RCC patients who had DCR (+) rather than those who progressed.Early decline in serum CRP, neutrophil and NLR levels in RCC patients who received pazopanib at the first month was significantly associated with disease control, assuming a predictive role for the first radiological assessment. However, there was no significant association between change in serum inflammatory marker levels and disease control in STS patients.

In this study, we aimed to determine the factors which affect post-progression survival (PPS) and overall survival (OS) in patients with metastatic colorectal cancer.87 patients with metastatic colorectal cancer had been followed up with palliative care due to disease progression or ECOG performance status after receiving at least two cycles of chemotherapy. PPS was estimated as the time between the last progression date and last control or death date in patients who were followed up with palliative care.87 patients with metastatic colorectal cancer were included in the study. Evaluation with multivariate analysis of factors affecting PPS revealed a significantly longer PPS (10.8 weeks) in patients with ECOG score 0 or 1 than the PPS of patients with ECOG score 2-5 (3 weeks) (p=0.01). It was also found that PPS was 14.4 weeks in patients with CEA levels5ng/ml,while it was 6.7 weeks in patients with CEA levels ≥5 ng/ml (p=0.001) and PPS was 13.7 weeks in patients with controlled disease after first-line chemotherapy while it was 8 weeks in patients with progression (p=0.03); both were statistically significant. No significant association was found between PPS and age, gender, tumor location, sites of metastasis, and RAS status.ECOG performance status score of 0-1, CEA levels below 5 ng/ml, and disease control with first-line chemotherapy are related to longer PPS in patients with metastatic colorectal cancer.

Effective skeletal muscle tissue engineering relies on control over the scaffold architecture for providing muscle cells with the required directionality, together with a mechanical property match with the surrounding tissue. Although recent advances in 3D printing fulfill the first requirement, the available synthetic polymers either are too rigid or show unfavorable surface and degradation profiles for the latter. In addition, natural polymers that are generally used as hydrogels lack the required mechanical stability to withstand the forces exerted during muscle contraction. Therefore, one of the most important challenges in the 3D printing of soft and elastic tissues such as skeletal muscle is the limitation of the availability of elastic, durable, and biodegradable biomaterials. Herein, we have synthesized novel, biocompatible and biodegradable, elastomeric, segmented polyurethane and polyurethaneurea (TPU) copolymers which are amenable for 3D printing and show high elasticity, low modulus, controlled biodegradability, and improved wettability, compared to conventional polycaprolactone (PCL) and PCL-based TPUs. The degradation profile of the 3D printed TPU scaffold was in line with the potential tissue integration and scaffold replacement process. Even though TPU attracts macrophages in 2D configuration, its 3D printed form showed limited activated macrophage adhesion and induced muscle-like structure formation by C2C12 mouse myoblasts in vitro, while resulting in a significant increase in muscle regeneration in vivo in a tibialis anterior defect in a rat model. Effective muscle regeneration was confirmed with immunohistochemical assessment as well as evaluation of electrical activity produced by regenerated muscle by EMG analysis and its force generation via a custom-made force transducer. Micro-CT evaluation also revealed production of more muscle-like structures in the case of implantation of cell-laden 3D printed scaffolds. These results demonstrate that matching the tissue properties for a given application via use of tailor-made polymers can substantially contribute to the regenerative outcomes of 3D printed tissue engineering scaffolds. Keywords: 3D printing; engineered muscle; polyurethane; polyurethaneurea; skeletal muscle; tibialis anterior defect.

In this study, we aimed to compare the data of sunitinib and pazopanib used in the first-line treatment of metastatic renal cell carcinoma (RCC) cases and to evaluate the effective factors in terms of survival.The records of 125 patients with metastatic RCC admitted between January 2005 and February 2018 were retrospectively analyzed and 63 patients who received pazopanib or sunitinib were included in the study while 62 patients were excluded due to insufficient data. Clinical and histological characteristics, treatment responses, progression-free survival (PFS), and overall survival (OS) of the patients were compared.Patients with metastatic RCC who received pazopanib or sunitinib as tyrosine kinase inhibitors (TKI) in first-line treatment were analyzed; 45 (71.4%) were male while 18 (28.6%) were female, and the median age was 60. 43 (68.3%) patients were treated with sunitinib and 20 (31.7%) with pazopanib. PFS ​​of pazopanib and sunitinib were 10.6 and 7.2 months, respectively. Median OS was 14.5 months in patients receiving pazopanib and 13.6 months in those receiving sunitinib. There was no statistical difference in PFS and OS between both treatments. The median OS of clear-cell RCC was 15.2 months, while of non-clear-cell RCC was 7.7months.High ECOG score, non-clear-cell histology, presence of liver metastasis in metastatic RCC patients were found to be associated with shorter OS and PFS. Sunitinib and pazopanib produced similar OS and PFS rates in first-line treatment of metastatic RCC.

This study aims to determine opinions of students who stay in private student residences about administrative problems. The study is made using descriptive scanning model and since 5 of the 16 student residences operating in Elazığ in 2011-2012 academic year did not permit questionnaire application, population of the study is composed of 1200 students staying in the remaining 11 student residences in Elazığ. Sample of the study is composed of 498 students chosen with simple random sampling method from among students staying in the said 11 residences. For collection of data, a questionnaire titled "opinions of students staying in private student residences about administrative problems" was used which was developed by the researcher. With the data obtained, arithmetic average, standard deviation, t test, one way analysis of variance were made. According to findings of the research 47.2% of the students find food prices high. Officers working in the residences are behaving towards students respectfully in general. Administrators are dealing with students very much at sometimes level. Sufficient education environment for studying according to student number can sometimes be found.

The aim of this study is to determine the perceptions of school administrators and guidance teachers on the effectiveness of implementation process of guidance and psychological counselling services at primary schools. Through a survey method 56 principals, 110 vice-principals and 56 guidance teachers at 56 public schools in central town of Elazığ during the academic year of 2010-2011. The number of total participants taking part in the research is 138. The results show that the perception levels of female administrators and guidance teachers are higher than male administrators and guidance teachers on the effectiveness of implementation process of guidance and psychological counselling. On the other hand, the perception levels of administrators and guidance teachers having 1-5 years of service group are higher than those having 11-15, 16-20, and 21 and over years of service groups in respect of the effectiveness of the implementation process of guidance and psychological counselling.

This study aimed to reveal the relationship between the level of galectin-3 expression and the depth of response to neoadjuvant therapy in bladder tumor tissue with muscle invasion revealed by transurethral biopsy.The percentage of galectin-3 staining in transurethral biopsy tissue with muscle invasion was determined by immunohistochemistry. The patients were divided into two groups: the down-staging (+) group consisting of patients with pathological complete response or non-invasive bladder cancer, and the down-staging (-) group consisting of patients with stage 2 and above.There were 11 patients in the down-staging (+) group and 12 patients in the down-staging (-) group. There was no significant difference between the two groups in terms of median age, gender, smoking, clinical stage at the time of diagnosis, distribution of carboplatin or cisplatin used as a platinum agent. Galectin-3 was positive in 2 patients (18.2%) in the group where down-staging was achieved with neoadjuvant therapy, while it was positive in 9 patients (75%) in the other group (p = 0.01). The median follow-up period of the patients was 31.6 months (95% CI 25.1-39.3). Overall survival was 43.4 months in the down-staging (+) group (95% CI 25.1-61.6) and 31.6 months in the down-staging (-) group (95% CI 12.7-50.6). Although there was a numerical difference, it did not reach statistical significance (p=0.37).The rate of down-staging after platinum-based neoadjuvant chemotherapy is significantly higher in patients with low galectin-3 staining in transurethral bladder biopsy tissue.

We aimed to assess whether skeletal muscle loss during EGFR thyrosine kinase inhibitor therapy of advance non-small cell lung cancer patients is an independent prognostic factor for progression-free survival (PFS) and overal survival (OS).A total of 45 patients who had computed tomography images were retrospectively evaluated at the diagnosis and during the treatment period before progression occurs.During treatment 19 patients (42.2%) had skeletal muscle loss. Objective response rates in muscle loss group and muscle stable group were 36.8% and 73.0%, respectively (p0.01). Median follow-up time was 18.9 months (14.8-32.1). Median PFS was 14.7 months (95% CI 12.1-17.3) in muscle stable group and 7.6 months (95% CI 6.7-8.5) in muscle loss group (p0.01). Median OS was 18.3 months (95% CI 16.5-20.2) in muscle loss group while it was 30.1 months (95% CI 22.1-38.2) in muscle stable group (p0.01). In multivariate analysis for both PFS and OS, skeletal muscle loss was an independent prognostic factor. Hazard ratios (HR) for PFS and OS were 12.2 (95% CI 4.3-34.4) and 3.51 (95% CI 1.41-8.73) respectively.On CT imaging skeletal muscle loss before progression is an independent prognostic factor for both PFS and OS in advance non-small cell lung cancer patients who received EGFR tyrosine kinase inhibitor therapy.

Study question Do livebirth rate (LBR), obstetric and perinatal outcomes vary between frozen embryo transfers (FET) in the first or subsequent menstrual cycles following a freeze-all approach? Summary answer Immediate FET has a higher LBR and similar perinatal outcomes than delayed FET. Quantitative synthesis of available literature shows an increased LBR with immediate transfer. What is known already Whether FET should be done in the first menstrual cycle following oocyte collection (OC) is controversial and the duration of a possible detrimental effect of supraphysiological sex steroid levels on pregnancy outcome is unknown. A multinational survey centers showed that, 61% of clinicians prefer to wait for a washout period before proceeding to FET, even after a failed fresh embryo transfer. Limited number of studies compared FET in the first menstrual cycle with delayed FET in a subsequent cycle with varying results. There is limited data on obstetric outcomes of pregnancies resulting from FET in the first menstrual cycle. Study design, size, duration 198 women who underwent a freeze-all cycle followed by FET between July 2017 and June 2020 were included. 119 FET in the first menstrual cycle (30 days from oocyte collection) were retrospectively compared. MEDLINE was searched on 01 January 2021 using relevant keywords. Cohort studies comparing immediate versus delayed transfer following freeze all cycles were included and quantitative summary for LBR was obtained. Participants/materials, setting, methods Freeze-all was undertaken when (i) the woman is deemed to be at high risk for OHSS, (ii)serum progesterone level is > 1.5 ng/ml on the day of trigger, (iii)preimplantation genetic testing is planned, (iv)the woman will undergo surgery prior to ET, (v)couple preference. Main results and the role of chance Baseline characteristics were similar between the groups except for antral follicle count (22 vs 18, MD = 5, 95% CI = 0 to 8), and number of metaphase-two oocytes (13 vs 10, MD = 3, 95% CI = 1 to 6) all of which were significantly higher in the immediate transfer group. Clinical pregnancy rate (CPR) per ET was similar in two groups (50.4% vs 44.3%, RR = 1.14, 95% CI = 0.84 to 1.54). Miscarriage rate per pregnancy was significantly lower (12.3 vs 31.1, RR = 0.40, 95% CI = 0.19 to 0.84) and LBR per ET was significantly higher (42.9 vs 26.6, RR = 1.61, 95% CI = 1.06 to 2.46) in the immediate transfer group. Median gestational age at delivery was similar (267.5 (262.5–273) vs 268 (260–271.5) days, MD = 1.00, 95% CI= –4.00 to 5.00). Median birthweight was significantly higher in the delayed transfer group (3520 vs 3195 grams, MD= –300, 95% CI= –660 to –20 grams). Birthweight percentile, height at birth and head circumference were similar between groups. Literature search revealed 1712 studies from which nine were eligible for quantitative summary. Cumulative risk ratio showed a 10% increase in LBR with immediate transfer compared to delayed transfer (RR = 1.10, 95% CI = 1.01 – 1.20, I2=67%, 17369 embryo transfers). Limitations, reasons for caution Our study is limited by its retrospective design and relatively limited sample size for multivariate analyses. Yet, it is reassuring that the majority of our findings are consistent with previous publications. Wider implications of the findings: The hypotheses generated by our retrospective findings, i.e., FET in the immediate menstrual cycle resembling fresh ETs with strong trends towards lower birthweight and lower incidence of preeclampsia is noteworthy for the design of future studies, and these outcomes should be followed and reported. Trial registration number None

Skeletal muscle is an electrically and mechanically active tissue that contains highly oriented, densely packed myofibrils. The tissue has self-regeneration capacity upon injury, which is limited in the cases of volumetric muscle loss. Several regenerative therapies have been developed in order to enhance this capacity, as well as to structurally and mechanically support the defect site during regeneration. Among them, biomimetic approaches that recapitulate the native microenvironment of the tissue in terms of parallel-aligned structure and biophysical signals were shown to be effective. In this study, we have developed 3D printed aligned and electrically active scaffolds in which the electrical conductivity was provided by carbonaceous material (CM) derived from algae-based biomass. The synthesis of this conductive and functional CM consisted of eco-friendly synthesis procedure such as pre-carbonization and multi-walled carbon nanotube (MWCNT) catalysis. CM obtained from biomass via hydrothermal carbonization (CM-03) and its ash form (CM-03K) were doped within poly(ɛ-caprolactone) (PCL) matrix and 3D printed to form scaffolds with aligned fibers for structural biomimicry. Scaffolds were seeded with C2C12 mouse myoblasts and subjected to electrical stimulation during the in vitro culture. Enhanced myotube formation was observed in electroactive groups compared to their non-conductive counterparts and it was observed that myotube formation and myotube maturity were significantly increased for CM-03 group after electrical stimulation. The results have therefore showed that the CM obtained from macroalgae biomass is a promising novel source for the production of the electrically conductive scaffolds for skeletal muscle tissue engineering.