Upfront resection versus no resection of the primary tumor in patients with synchronous metastatic colorectal cancer: the randomized phase III CAIRO4 study conducted by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group.

BACKGROUND: Upfront primary tumor resection (PTR) has been associated with longer overall survival (OS) in patients with synchronous unresectable metastatic colorectal cancer (mCRC) in retrospective analyses. The aim of the CAIRO4 study was to investigate whether the addition of upfront PTR to systemic therapy resulted in a survival benefit in patients with synchronous mCRC without severe symptoms of their primary tumor. PATIENTS AND METHODS: This randomized phase III trial was conducted in 45 hospitals in The Netherlands and Denmark. Eligibility criteria included previously untreated mCRC, unresectable metastases, and no severe symptoms of the primary tumor. Patients were randomized (1 : 1) to upfront PTR followed by systemic therapy or systemic therapy without upfront PTR. Systemic therapy consisted of first-line fluoropyrimidine-based chemotherapy with bevacizumab in both arms. Primary endpoint was OS in the intention-to-treat population. The study was registered at ClinicalTrials.gov, NCT01606098. RESULTS: Between August 2012 and February 2021, 206 patients were randomized. In the intention-to-treat analysis, 204 patients were included (n = 103 without upfront PTR, n = 101 with upfront PTR) of whom 116 were men (57%) with median age of 65 years (interquartile range 59-71 years). Median follow-up was 69.4 months. Median OS in the arm without upfront PTR was 18.3 months (95% confidence interval 16.0-22.2 months) compared with 20.1 months (95% confidence interval 17.0-25.1 months) in the upfront PTR arm (P = 0.32). The number of grade 3-4 events was 71 (72%) in the arm without upfront PTR and 61 (65%) in the upfront PTR arm (P = 0.33). Three deaths (3%) possibly related to treatment were reported in the arm without upfront PTR and four (4%) in the upfront PTR arm. CONCLUSIONS: Addition of upfront PTR to palliative systemic therapy in patients with synchronous mCRC without severe symptoms of the primary tumor does not result in a survival benefit. This practice should no longer be considered standard of care.

The Impact of Dose Rate on the Tumor Microenvironment Using Flattening-filter-free Beams.

AIMS: Recently, dose delivery technology has rapidly evolved with flattening filter-free beams (FFF), and the biological effects of high dose rates are a matter of interest. We hypothesized that FFF beams at different dose rates obtained with modern linear accelerators have different effects on the TME. MATERIALS AND METHODS: The B16-F10 melanoma syngeneic tumor model was established, and mice were randomized to 2 different doses (2 Gy and 10 Gy) and 3 different dose rates (1 Gy/min, 6 Gy/min, and 14 Gy/min) along with the control group. Euthanasia was performed on the seventh day after RT, and intracardiac blood was collected for a comet assay. Tumors were harvested and examined histomorphologically and immunohistochemically. Statistical analyses were performed using SPSS software version 23 (SPSS Inc., Chicago, IL, USA). RESULTS: The daily growth rate was uniform, and no difference was observed between tumor volumes across all three dose rates for each dose. Deoxyribonucleic acid (DNA) damage in blood mononuclear cells was not affected by dose or dose rate. In the TME histomorphological examination, the number of mitosis is less in the 10 Gy arm, whereas the pleomorphism score was greater. Nevertheless, varying dose rates had no effect on the number of mitosis or the pleomorphism score. The severity of the inflammation, cell densities in the TME, and expression of immunohistochemical markers were comparable across all doses and dose rates. CONCLUSION: In our study involving the B16-F10 syngeneic tumor model, varying dose rates obtained with FFF beams had no effect on tumor volume, blood mononuclear cell DNA damage, or TME parameters. However, in order to fully understand the biological impacts of novel techniques, our study should be validated with alternative preclinical setups.

Safety and efficacy of nivolumab therapy in patients with metastatic renal cell carcinoma and impaired kidney function.

INTRODUCTION: Patients with renal insufficiency, usually defined as those with creatinine clearance < 40 mL/min, were excluded from pivotal clinical trials, especially in studies involving nivolumab therapy in patients with renal cell carcinoma (RCC). The aim of the study is to evaluate the efficacy and safety of nivolumab in patients with metastatic RCC (mRCC) stratified according to creatinine clearance. MATERIAL AND METHODS: Data from mRCC patients treated with nivolumab were retrospectively analyzed. Patients were classified into two categories according to their estimated glomerular filtration rate (eGFR); the first category (C1) included patients with eGFR < 40 mL/min/1.73 m2 and the second category (C2) included those with eGFR ≥ 40 mL/min/1.73 m2. RESULTS: Of the 95 patients enrolled, 1. group included 26 patients (27.4%) and 2. group included 69 patients (72.6%). None of the pts in category 1 were on hemodialysis. Overall incidence of adverse events was not statistically different between the two groups (P = .469). The overall response rate ORR was 50% in the first group and 42.0% in the second group (P = .486). Median overall survival (OS) was longer with 23.3 months in the 2. group versus 11 months in the 1. group (P = .415). CONCLUSION: Renal insufficiency is a common problem in patients with advanced renal cancer since they often undergo nephrectomy and their renal function may also worsen while receiving tyrosine kinase inhibitor therapy. We found that there is no significant difference in the safety and efficacy of nivolumab treatment between two groups. Nivolumab appears to be a safe and effective agent in patients with renal impairment.

The preoperative predictive factors for pathological T3a upstaging and positive surgical margin of clinical T1 renal cell carcinoma.

OBJECTIVES: The objective of this study is predict positive surgical margin (PSM) and pathological T3a (pT3a) upstaging in patients with clinical T1 (cT1) renal cell carcinoma (RCC). MATERIALS AND METHODS: 159 patients who underwent radical nephrectomy (RN) or partial nephrectomy (PN) for RCC. Patients' demographic, laboratory, radiological and pathological data that could predict PSM and pT3a upstaging pre-operatively were evaluated. The categorical and continuous variables were compared between the patient groups with or without PSM and/or pT3a upstaging using Pearson's chi-square test, and independent samples t-test or the Mann-Whitney U test, respectively. RESULTS: PT3a upstaging was detected in 32 (20.1%) patients, and PSM was detected in 28 (17.6%) patients. PT3a upstaging was detected in 27 and 5 patients who underwent open surgery and laparoscopic surgery, respectively (P < .001). In addition, pT3a upstaging was detected in 6 and 26 patients who underwent RN and PN, respectively (P < .001). Peritumoral fatty tissue thickness was 11.97 and 15.38 in the pT1 and pT3a patient groups, respectively (P = .022). In patients with pT3a upstaging, tumor size was larger, and renal nephrometry score and systemic immune-inflammation index (SII) were higher (P < .001, P < .001, and P = .022, respectively). It was determined that De Ritis ratio (DRR) and albumin-to-alkaline phosphatase (ALP) ratio (AAPR) parameters had significant prognostic values in predicting PSM (P = .024, and P = .001, respectively). ROC analysis indicated that tumor size predicted pT3a upstaging with 100% sensitivity and 98.6% specificity when its cut-off value was taken as 6.85 mm (AUC: 1.000, P < .001). In addition, logistic regression analysis revealed AAPR and DRR as significant predictors of PSM (P < .001, and P = .009, repsectively). CONCLUSION: The findings of this study indicated that the surgical technique of choice and the type of operation, tumor size, RNS value, peritumoral fatty tissue thickness, HU values of peritumoral and tumor side fatty tissues, and DRR and SII values can predict pT3a upstaging of patients with cT1 RCC, and that AAPR and DRR values can predict PSM.

The impact of fragmented QRS on clinical findings and outcomes in children with dilated cardiomyopathy with or without left ventricular non-compaction.

OBJECTIVE: The aim of this study is to investigate the frequency of fragmented QRS and its associations with clinical findings and prognosis in children diagnosed with dilated cardiomyopathy with or without left ventricular non-compaction. METHODS: This retrospective study was conducted between 2010 and 2020. Patients with dilated cardiomyopathy were classified into two groups according to the presence of left ventricular non-compaction: Dilated cardiomyopathy with left ventricular non-compaction and dilated cardiomyopathy without left ventricular non-compaction. Patients were also divided into two groups according to the presence of fragmented QRS (fragmented QRS group and non-fragmented QRS group). RESULTS: Twenty-three of 44 patients (52.3%) were male. Among left ventricular non-compaction patients, the fragmented QRS group had more complex ventricular arrhythmias (p = 0.003). Patients with fragmented QRS had a significantly higher rate of major adverse cardiac events and/or cardiac death in both cardiomyopathy groups (p = 0.003 and p = 0.005). However, the rate of major adverse cardiac events and/or cardiac death was similar between dilated cardiomyopathy patients with and without left ventricular non-compaction. Multivariate logistic regression analysis showed that the presence of fragmented QRS strongly predicts major adverse cardiac events and/or cardiac death (odds ratio, 31.186; 95% confidence interval, 2.347-414.307). Although the survival rates between cardiomyopathy groups were similar, patients with fragmented QRS had a markedly lower survival rate during the follow-up period, as mean of 15 months (p = 0.001). CONCLUSION: Our study showed that the presence of fragmented QRS may be an important ECG sign predicting an major adverse cardiac event and/or cardiac death in patients with dilated cardiomyopathy. We believe that recognising fragmented QRS could be valuable in forecasting patient prognosis and identifying high-risk patients who require additional support.

Involved-site Radiotherapy Delineation Dilemmas in the Treatment of Adult Hodgkin Lymphoma: Turkish Society for Radiation Oncology Hematological Oncology, Pediatric Oncology and TBI Study Group Case-based Questionnaire Review (TROD 03-005).

AIMS: The International Lymphoma Radiation Oncology Group (ILROG) defined involved-site radiotherapy (ISRT) guidelines. These rules offer a certain variability that allows for autonomous decision-making in diverse clinical settings. However, this flexibility also gives rise to conflicts about the selection of treatment fields in the daily decision-making process. The aim of this study was to show the extent of interobserver variability when ILROG-ISRT recommendations were used in different clinical scenarios. MATERIALS AND METHODS: The 10-question survey used in our study consisted of two parts (part A and part B) and was prepared by four senior radiation oncologists experienced in the haemato-oncology field. The results were presented by stratifying according to clinical experience (<10 years, ≥10 years). Binomial tests (one-sided) were conducted to assess whether answers for each group and the whole group reached a consensus. RESULTS: Twenty-six radiation oncologists, 13 of whom had less than 10 years of experience and 13 seniors, participated in the survey. Eighty per cent of respondents thought ILROG did not bring sufficient solutions for all clinical scenarios but offered solutions in some cases. In different case-based scenarios, the consensus among the respondents decreased down to 38%. Senior radiation oncologists were found to have more doubts about the adequacy of current guidelines. CONCLUSIONS: ILROG guidelines allow for a high degree of variability in real-life clinical scenarios and different interpretation of the recommendations may lead to increased toxicity and recurrences. Therefore, there is a need for refinement in ISRT delineation strategies. On behalf of the Turkish Society for Radiation Oncology Hematological Oncology, Pediatric Oncology and TBI Study Group, we are planning to carry out further educational contouring sessions to detect the interobserver variability in real-life contouring cases.

A mixed-apoptotic effect of Jurinea mesopotamica extract on prostate cancer cells: a promising source for natural chemotherapeutics.

This research investigates the potential use of Jurinea mesopotamica Hand.-Mazz. (Asteraceae) in cancer treatment. In this study, a plant extract was prepared using all parts of J. mesopotamica, and its effect on the proliferation of cancer and normal cells was tested using the MTT method. It was found to have a selective cytotoxic effect on prostate cancer cells, with the lowest IC50 (half-maximal inhibitory concentration) of 10µg/mL found in the butanol extract (JMBE). The extract suppressed the proliferation of prostate cancer cells (67 %), disrupted organelle integrity (49 %), increased reactive oxidative stress (66 %), and triggered cell death (51 %). In addition, apoptotic gene expressions and protein levels increased, and the profile of amino acids related to energy metabolism was elevated. Based on LC-MS/MS results, the plant contained higher levels of flavonoids, including isoquercitrin, cosmosiin, astragalin, nicotiflorin, luteolin, and apigenin. These results suggest that J. mesopotamica has a selective effect on prostate cancer due to its high flavonoid content and might be a promising natural alternative for cancer treatment.

Hepatic insulin synthesis increases in rat models of diabetes mellitus type 1 and 2 differently.

Insulin-positive (+) cells (IPCs), detected in multiple organs, are of great interest as a probable alternative to ameliorate pancreatic beta-cells dysfunction and insulin deficiency in diabetes. Liver is a potential source of IPCs due to it common embryological origin with pancreas. We previously demonstrated the presence of IPCs in the liver of healthy and diabetic rats, but detailed description and analysis of the factors, which potentially can induced ectopic hepatic expression of insulin in type 1 (T1D) and type 2 diabetes (T2D), were not performed. In present study we evaluate mass of hepatic IPCs in the rat models of T1D and T2D and discuss factors, which may stimulate it generation: glycaemia, organ injury, involving of hepatic stem/progenitor cell compartment, expression of transcription factors and inflammation. Quantity of IPCs in the liver was up by 1.7-fold in rats with T1D and 10-fold in T2D compared to non-diabetic (ND) rats. We concluded that ectopic hepatic expression of insulin gene is activated by combined action of a number of factors, with inflammation playing a decision role.

Assessment of sensitivity to the anesthesia in a diabetic rat model.

OBJECTIVE: Diabetes mellitus and glucose regulation are important in deciding on surgical intervention in pre-surgical assessments. In our study, we aimed to investigate the correlations between the induction time of anesthesia, glucose level, and weight in a diabetic rat model. MATERIALS AND METHODS: Weight-matched adult male Wistar rats were grouped as control (n=8) and diabetic (n=8). In the latter group, diabetes was induced with a single intraperitoneal injection of 50 mg/kg streptozotosin. 72 hours after the injection, animals possessing a blood glucose concentration above 300 mg/kg were considered diabetic. The weights and blood glucose levels were observed for 7 days. In the end, 80 mg/kg ketamine and 12 mg/kg xylazine were administered to both groups, and the induction time of anesthesia was recorded. The success of anesthesia was confirmed with toe pinching by using a clamp. The Student's t- and Pearson's correlation tests were used for statistical analyses. RESULTS: The induction time of anesthesia was significantly reduced in the diabetic group compared to the controls (p<0.01). Diabetic animals weighed less than the control group (p<0.01). The correlation analysis in the diabetic group showed that the weight and blood glucose level of animals did not influence the induction time of anesthesia (respectively, p=0.80, r: 0.150; p=0.68, r: -0.300). A negative correlation between blood glucose concentration and weight was found in diabetics (p<0.05, r: -0.828). CONCLUSIONS: The dosage of anesthetic agents is important in the effectiveness of anesthesia, and surgical complications. Since our results indicate the susceptibility of diabetics to anesthesia, we suggest that the dose of anesthetics should be finely adjusted considering the presence of diabetes.

Gamma radiation shielding properties for polymer composites reinforced with bismuth tungstate in different proportions.

In this study, inorganic compound (Bi2(WO4)3) was added into the composite to improve the radiation shielding properties of polymer composite. A polymer matrix was prepared by combining unsaturated polyester resin with methyl ethyl ketone peroxide and cobalt octoate (6%), and Bi2(WO4)3 was added to this polymer matrix at different ratios as filling material. In order to investigate the gamma radiation attenuation properties of the obtained polymer composites, mass attenuation coefficients, radiation shielding efficiencies, radiation transmission factors, linear attenuation coefficients, half values layer, tenth values layer, mean free path values, effective atomic numbers and effective electron densities parameters were obtained. Experimental studies were carried out with the help of HPGe detector at 22 different energies emitted from 22Na, 54Mn, 57Co, 60Co, 133Ba, 137Cs, 152Eu and 241Am radioactive sources in the photon energy range of 59.5-1408.0 keV. Each obtained experimental result was compared with the theoretical results. It was observed that the sample encoded with BiWO20 is the best radiation shielding material among all studied composites (except 59.5 keV).

Fluorescent silica nanoparticles as nano-chemosensors for the sequential detection of Pb2+ ions and bacterial-spore biomarker dipicolinic acid (DPA) in aqueous solution.

Herein, we report fluorescein-labelled silica nanoparticles (FSNP) which serve as fluorescent nano-chemosensors for sequential detection of Pb2+ (which is a toxic heavy metal) and dipicolinic acid (DPA) (which is a distinctive indicator biomarker of bacterial spores) with high sensitivity and selectivity. The fluorescence of FSNP is quenched because of the complex formation between Pb2+ ions and surface amide groups, however, the fluorescence is recovered in contact with DPA, resulting from the association of DPA with surface bound Pb2+ ions. FSNP-Pb2+ complexes show high sensitivity towards DPA with a low detection limit of 850 nM which is approximately seventy times lower than the infectious dosage of bacterial spores (60 µM). Lateral flow test platform was further developed to show the applicability and practicability of our system.

Can anterolateral thigh flap be a rescuer in lower extremity injuries?

OBJECTIVE: The lower extremity contains a variety of functional structures therefore re-establishing soft tissue coverage in large-scale injuries is a challenging procedure. Microsurgery has made progress in reducing donor morbidity and achieving a functional and aesthetic appearance in recent years. This study aimed to apply anterolateral thigh (ALT) flap to tissue defects in the lower extremity and to discuss the results. PATIENTS AND METHODS: Twenty-three patients who were admitted to our hospital with lower extremity trauma and underwent ALT flap surgery due to soft tissue defect between November 2020 and March 2022 were included in the study. Patients' demographic data, the applied surgical procedure, the development of postoperative complications, and postoperative functional results were evaluated. RESULTS: Twenty-three patients were included in this research. The mean age of the patients was 36.56±14.67 (10-61). Of these patients, 3 were female (13%), and 20 were male (87%). The most common etiology was traffic accident (n=8, 34%), followed by gunshot injuries (n=5, 21%), electrical burn (n=4, 17%), open fractures (n=2, 7%), infection (n=2, 7%), diabetic foot (n=1, 4%), skin tumor (n=1, 4%). Flaps were raised from the contralateral extremity in twelve patients (52%) and on the ipsilateral extremity in eleven patients (48%). The average time from first trauma to free flap surgery was 10.7±5 days (4-22). The average postoperative hospitalization was 13.6 days (9-23 days). The average follow-up time of patients was 8 months (3-13 months). The donor site is closed with primary saturation in 19 patients (82%) and closed with split-thickness skin grafting in 4 patients (18%). Our overall success rate was 96%. We had only one total flap failure out of twenty-three patients (4%). CONCLUSIONS: ALT-free flap is an excellent choice for reconstructing lower extremity complex defects. For experienced surgeons, the ALT flap can be used successfully in the treatment of soft tissue defects of variable size in the lower extremity.

Diagnostic performance of FDG PET/MRI for cervical lymph node metastasis in patients with clinically N0 head and neck cancer.

OBJECTIVE: Treatment management in cases of head and neck squamous cell cancer (HNSCC) that are clinically negative for lymph node metastases (cN0) is still an important topic of discussion. There is increasing interest in sensitive imaging modalities that can detect the risk of occult metastases at levels below 20%. This study aimed to examine the efficacy of integrated positron emission tomography (PET)/magnetic resonance imaging (MRI) in determining neck nodal metastasis status in cN0 patients with HNSCC. PATIENTS AND METHODS: In this retrospective study, 44 patients who underwent neck dissection with the diagnosis of HNSCC between January 2018 and August 2020 were analyzed. Clinical examinations, including ultrasonography, were performed to identify cervical metastases in HNSCC patients with preoperative cN0. A nuclear medicine specialist visually evaluated the MRI, PET, and PET/MRI results. RESULTS: Histopathologically, 86.4% of patients were classified as N0. According to the histopathological results, MRI showed 50% sensitivity, 89.5% specificity, 91.8% negative predictive value (NPV), 42.8% positive predictive value (PPV) and 84% accuracy, while PET showed 83.3% sensitivity, 68.4% specificity, 96.2% NPV, 29.4% PPV and 70.4% accuracy. PET/MRI was more successful in distinguishing pathological N0 and N+ patients (83.3% sensitivity, 92.1% specificity, 97.2% NPV, 62.5% PPV and 90.9% accuracy). CONCLUSIONS: PET/MRI is more sensitive and has a higher NPV compared to MRI alone, while its sensitivity was found to be comparable to that of PET. In addition, with its ability to detect pathological N0 patients, PET/MRI may significantly decrease the number of unnecessary neck dissections.

Vincristine-associated total antioxidant and oxidant status of ovaries and in vitro nuclear oocyte maturation in dogs with canine transmissible venereal tumor.

The aim of this study is to evaluate the effects of scheduled vincristine sulfate therapy on canine oocyte quality and nuclear oocyte maturation, associated with total antioxidant and oxidant status of ovaries and Anti-Müllerian Hormone (AMH) concentrations in dogs with Canine Transmissible Venereal Tumor (CTVT). Six bitches suffering from CTVT and six healthy bitches were included in the study. Hemogram was carried out weekly. AMH measurements and ovariohysterectomy operations were performed after the termination of vincristine sulfate therapies. Tissue samples from ovaries were utilized for Malondialdehyde (MDA), reduced Glutathione (GSH), Superoxide Dismutase (SOD), Total Anti-oxidative Status (TAS), Total Oxidative Status (TOS) measurements, and Oxidative Stress Index (OSI) was calculated. Collected oocytes were evaluated for meiotic competence, after In Vitro Maturation (IVM) and parthenogenetic activation. No difference between the two groups was observed in hematologic parameters (P > 0.05). Meiotic stages of Germinal Vesicle Break Down (GVBD), Metaphase I (MI), and Metaphase II (MII) were significantly different between groups (P < 0.05). The number of oocytes reaching MII and meiotic resumption was lower in the CTVT group. Furthermore, AMH concentrations, oxidant parameters (OSI, TOS, and MDA), and antioxidant parameters (GSH, SOD, and TAS) were also statistically different between groups (P < 0.05). The results of this study show that vincristine sulfate application in the treatment of CTVT could alter oxidant/antioxidant status in ovaries. Apart from these, oocyte quality and IVM rates seem to decline related to gonadotoxicity. Moreover, AMH could be an important marker in the evaluation of oocyte qualities in bitches, as it is in women.

Erector spinae plane block prior to extracorporeal shock wave lithotripsy decreases fluoroscopy time and promise a comfortable procedure for renal stones: A prospective randomized study.

INTRODUCTION AND OBJECTIVES: To compare the efficacy of erector spinae plane block (ESPB) and intramuscular (i.m.) diclofenac sodium in regard to pain management and impact on stone-free status in patients undergoing SWL. PATIENTS AND MATERIALS: The study included patients who underwent SWL for kidney stones in our institution. The patients were randomly assigned to the ESPB (Group 1: n = 31) and i.m. 75 mg diclofenac sodium (Group 2: n = 30) groups. The demographic data of the patients, fluoroscopy time during SWL, number of need of targeting, total shocks given, voltage, stone free rates (SFR), analgesy method, number of SWL sessions, VAS score, stone location, maximum stone size, stone volume and Hounsfield unit (HU) were also recorded. RESULTS: A total of 61 patients were included the study. There was no statistically significant difference between the two groups according to stone size, volume and density, SWL duration, total shocks given, voltage, BMI, stone-free status and stone location. Fluoroscopy time and number of need for stone targeting were significantly lower in group 1 than group 2 (p = 0.002, p = 0.021, respectively). The VAS score was significantly lower for group 1 compared to group 2 (p < 0.001). CONCLUSIONS: We observed that the VAS score was lower in the ESPB group compared to i.m. diclofenac sodium group and although it was not statistically significant, we achieved a higher rate of stone-free status in the first session in ESPB group. Most importantly, the patients in the ESPB group were exposed to less fluoroscopy and radiation.

Reactive Extraction of Betaine from Sugarbeet Processing Byproducts.

Betaine from natural sources is still preferred over its synthetic analogue in secondary industries. It is currently obtained by expensive separation means, which is one of the main reasons for its high cost. In this study, reactive extraction of betaine from sugarbeet industry byproducts, that is, molasses and vinasse, was investigated. Dinonylnaphthalenedisulfonic acid (DNNDSA) was used as the extraction agent, and the initial concentration of betaine in the aqueous solutions of byproducts was adjusted to 0.1 M. Although maximum efficiencies were obtained at unadjusted pH values (pH 6, 5, and 6 for aqueous betaine, molasses, and vinasse solutions, respectively), the effect of aqueous pH on betaine extraction was negligible in the range of 2-12. The possible reaction mechanisms between betaine and DNNDSA under acidic, neutral, and basic conditions were discussed. Increasing the extractant concentration significantly increased (especially in the range of 0.1-0.4 M) the yields, and temperature positively (but slightly) affected betaine extraction. The highest extraction efficiencies (∼71.5, 71, and 67.5% in a single step for aqueous betaine, vinasse, and molasses solutions, respectively) were obtained with toluene as an organic phase solvent, and it was followed by dimethyl phthalate, 1-octanol, or methyl isobutyl ketone, indicating that the efficiency increased with decreasing polarity. Recoveries from pure betaine solutions were higher (especially at higher pH values and [DNNDSA] < 0.5 M) than those from vinasse and molasses solutions, indicating the adverse influence of byproduct constituents; however, the lower yields were not due to sucrose. Stripping was affected by the type of organic phase solvent, and a significant amount (66-91% in single step) of betaine in the organic phase was transferred to the second aqueous phase using NaOH as the stripping agent. Reactive extraction has a great potential for use in betaine recovery due to its high efficiency, simplicity, low energy demand, and cost.

A Dicationic BODIPY-Based Fluorescent Bactericide to Combat Infectious Diseases and to Eradicate Bacterial Biofilms.

Increased bacterial resistance against extensively used common disinfectants has begun to emerge. The discovery of disinfectants substituting the current commercially available ones is strongly needed. For this purpose, a dicationic BODIPY-based fluorescent amphiphile has been synthesized by specific molecular design. This quaternized BODIPY behaves as a broad-spectrum disinfectant against both Gram-positive and Gram-negative bacteria strains. It exhibits potent antimicrobial activity against tested microorganisms when compared with structurally similar disinfectant benzalkonium chloride (BAC). Moreover, it shows antibiofilm activity against Staphylococcus epidermidis with a minimum biofilm eradication concentration as low as 16 µg/mL. The interaction of this compound with the bacterial cell and genomic DNA was further evaluated by fluorescence spectroscopy and microscopy to follow cell internationalization and to clarify the mechanism of antibacterial action.

The role of cytokines and T-bet, GATA3, ROR-γt, and FOXP3 transcription factors of T cell subsets in the natural clinical progression of Type 1 Diabetes.

Th cells play an important role in pathogenesis of type 1 diabetes (T1D). Peripheral blood mononuclear cells were isolated from peripheral blood samples from newly diagnosed (ND), 1-year (1YD), and 5-year T1D (5YD) patients (n:8 of each group), 8 healthy controls (HC), and cultured for 24 h under unstimulated (US) and stimulated conditions. Cell ratios of Th1, Th2, Th17, Treg, and intracellular levels of IFN-γ, TNF-α, IL-10, TGF-ß, IL-5, IL-13, IL-17, and IL-21 cytokines were evaluated using the flow cytometry. mRNA expressions of transcription factors T-bet, GATA3, ROR-γt, and FOXP3 of these cells were determined by real-time PCR. Reduced CD4+CD25high cell ratios were detected in ND. CD4+CD25high cells were found to be reduced in ND and 1YD compared to HC under IL-2-stimulated conditions. Intracellular IFN-γ and TNF-α levels were low in all patients under US and IL-12-stimulated conditions. IL-17A and IL-21 were found to be high in patients with IL-6-stimulated conditions. Expressions of IL-10 and TGF-ß have been observed to be reduced in patients. Th1/Th2, Th17/Treg, and Th1/Treg ratios were higher in patient groups. FOXP3 and GATA3 mRNA expressions were found to be low in patients, while RORγt and T-bet mRNA levels were higher than HC. Th1, Th17, and Treg cells and their cytokines have been shown to be associated with type 1 diabetes.

The Combined Effect of Melatonin Implant and Removal of Buck Seminal Plasma on Cryopreservation During the Nonbreeding Season.

This study aimed to determine how melatonin (MT) and seminal plasma affected the freezability of buck sperm during the nonbreeding season. Semen was collected from eight bucks before (pre-MT) and after (post-MT) MT application in the nonbreeding season. Individual ejaculates were collected from the bucks, split into two equal groups according to the removal of seminal plasma (SP) (-) or nonremoval of SP (+). For washing, the groups of ejaculates were centrifuged, and the supernatant was separated, SP (-) and SP (+) ejaculates were diluted, then frozen. Semen samples were examined for sperm motility, plasma membrane integrity, defective acrosomes, DNA fragmentation, and mitochondrial membrane function at the native and post-thaw stages. When the general average post-thaw motility (p < 0.01), plasma membrane (p < 0.05), acrosome (p < 0.05), and DNA integrity rates (p < 0.05) and mitochondrial membrane potential (MMP) (p < 0.01) were evaluated, it was seen that MT administration caused a statistically significant improvement. The dramatic effect of nonremoval of seminal plasma on motility and plasma membrane integrity is more clearly observed in individual semen samples frozen in the pre-MT group (p < 0.05). Also, it was observed that removing seminal plasma in the post-MT group caused even milder post-thaw acrosome damage compared with the SP (+) group (p < 0.05). The effect of removing seminal plasma was not observed in terms of DNA integrity and MMP rates in pre- and post-MT groups. As a result, it was concluded that MT application and removal of seminal plasma in the nonbreeding season result in improvement in the freezability of buck semen.