45S5 Bioactive Glass-Ointment Positively Effects on Wound Healing in Rats by Regulating TNFα, Il-10, VEGF, and TGFß.

AIM: This study aimed to investigate the effects of 45S5 bioactive glass-ointment (BG) on cutaneous wound healing in rats at the molecular, biochemical, and histopathological levels. MATERIALS AND METHODS: Thirty-two rats were divided into four groups (n = 8): Control, Sham, BG, and DEX (Dexpanthenol). While no wound treatment was applied to the CONTROL, a wound model was created in the Sham, and no treatment was applied. A wound model was created for other groups, and BG and DEX were applied locally for 21 days. During the 21-day experiment period, feed and water consumption and weight changes were observed. Wound areas were calculated on days 0, 3, 7, 4, and 21. Following treatment, the rats were euthanized and tissues from the wound area and blood samples were collected. While the expression levels of tumor necrosis factor-alpha (TNFα), Interleukin 6 (IL6), Interleukin 10 (IL10), transforming growth factor-beta (TGFß), and vascular endothelial growth factor (VEGF) genes were determined by qPCR, the levels of TNFα, IL6, and IL10 proteins were measured by ELISA. RESULTS: It was observed that the BG group showed anti-inflammatory activity by suppressing TNFα levels and stimulating IL-10. In addition, it was determined that BG increased fibroblast activity and vascularization. CONCLUSION: Current findings showed that topical application of BG has anti-inflammatory effects, while also accelerating healing by increasing vascularity and making positive contributions to tissue healing.

The effects of the feeding duration of propylene glycol on major meat quality parameters and substantial proteins in the muscle of Akkaraman lambs.

In this study, the effects of propylene glycol (PG) on meat quality and molecular pathways related to energy metabolism in longissimus lumborum muscle on lambs were evaluated. Seventy-two lambs were divided into three groups consisting of 60th, 90th, and 120th of slaughter days. The dosage of the PG and slaughter days were the variables used in the study. Eight animals were slaughtered from each group on each day. The meat quality parameters (e.g., pH, protein, fatty acid profile) and IGF-1, IGFBP4, and DGAT1 (i.e., mRNA and protein levels) were evaluated. The pH 45 min post-slaughter was higher in PG groups on 120th day. On the 4th day after slaughter, the b value was the lowest in the PG3, while 7th day after slaughter it was highest in Con and PG3 on 90th day. The total n3 and n6 were lowest and the NV was highest on 120th day. The IGFBP4 was upregulated in the PG groups on all of the slaughter days. The DGAT1 was upregulated in the PG3 on the 90th day. The IGF-1, DGAT1, IGFBP4 protein levels were found to have increased in the PG3 on 90th day. The IGFBP4 was found to have decreased in the PG3 on 120th day. According to the results of the study, the oral administration of the PG at the 3 mL/kg live weight0.75 for at least 120 days may have positive effects on meat quality in lambs through the IGF-1, DGAT1, and IGFBP4 genes and the proteins encoded by these genes.

Expression patterns of inflammatory and oxidative stress-related genes in the uterine and ovarian tissues of dogs diagnosed with pyometra based on cervical patency status.

This study aimed to investigate the expression patterns of genes associated with inflammation and oxidative stress in ovarian and uterine tissues of dogs with pyometra, categorized by cervical status (open cervix or closed cervix), which influences disease severity. The control group comprised healthy animals undergoing elective ovariohysterectomy. Tissue inflammatory gene expression and Malondialdehyde (MDA) levels were determined while microbial and histopathological examinations were conducted, along with immunohistochemical evaluations. In the closed-cervix group, uterine TNF and IL6 were upregulated approximately 10-fold while IL10 was upregulated nearly 5-fold. TNF expression differed remarkably between the pyometra groups. In the closed-cervix group, PTGS2 and HMOX1 were upregulated approximately 5-fold whereas NFE2L2 expression was downregulated. The closed-cervix group also had the highest uterine MDA levels. Regarding ovarian tissue, MDA levels were higher in the closed-cervix group than in the open-cervix group while IL10 expression was lower in the closed-cervix group than the open-cervix group. In the closed-cervix group, NFE2L2 was downregulated whereas HMOX1 was upregulated. Uterine TNF levels were positively correlated with IL6, IL10, PTGS2, and HMOX1, but negatively correlated with NFE2L2. IL6 was positively correlated with IL10, PTGS2, and HMOX1. NFE2L2 was negatively correlated with IL6 and HMOX1. IL10 was positively correlated with PTGS2 and HMOX1. MDA was positively correlated with TNF, IL6, IL10, PTGS2, NFE2L2, and HMOX1. TNF levels were positively correlated with ovarian PTGS2, and with IL6 and NFE2L2. MDA was positively correlated with PTGS2 and HMOX1. MDA could be an important biomarker for understanding the severity of pyometra. Moreover, TNF expression and its relationships with various studied parameters such as IL10 may contribute to treatment and prognostic biomarker studies in closed-cervix pyometra pathology.

Expression patterns and distribution of aquaporin water channels in cervix as a possible mechanism for cervical patency in bitches affected by pyometra.

Pyometra is a life-threatening disease, the severity of which depends on cervical patency status. This study investigated cervical inflammation status as well as the expression patterns and localization of aquaporin (AQP1, AQP2, AQP3, AQP5, and AQP9), and hormone receptors in cervical tissue that influences canine pyometra. Of the 36 animals enrolled in the study, 24 were diagnosed with pyometra and separated into two groups: open cervix pyometra and close cervix pyometra, while 12 healthy animals presented for elective ovariohysterectomies were allocated into the control group. Surgical treatment was performed for treatment of pyometra. After each operation, cervix samples were collected and analyzed for AQP and hormone receptor expression patterns determined by qPCR and protein expression by means of immunohistochemistry. Blood samples were also collected to determine serum progesterone concentrations. AQP9 expression was downregulated approximately 3-fold while and PGR expression was downregulated more than 2 fold in both pyometra groups compared to the control group. AQP3 and AQP5 gene expression levels were upregulated more than 3 fold in the open-cervix pyometra group than the closed-cervix pyometra group (P < 0.05). This is the first study to describe the expression patterns and immunolocalization of AQPs in canine cervical tissue based on pyometra patency status and to report AQP3 and AQP5 expression in cervical tissue linked to cervical patency.

Considering potential roles of selected MicroRNAs in evaluating subclinical mastitis and Milk quality in California mastitis test (+) and infected bovine milk.

This study investigates the relationships between subclinical mastitis and milk quality with selected microRNAs in cow milk. California Mastitis Test (CMT)-positive (n = 20) and negative (n = 20) samples were compared (Experiment I). Additionally, samples with CMT-positive but microbiological-negative, as well as positive for only Staphylococcus subspecies (Staph spp.) and only Streptococcus subspecies (Strep spp.) were examined (Experiment II). Four groups were formed in Experiment II: Group I (CMT and microbiological-negative) (n = 20), Group II (CMT-positive but microbiological-negative) (n = 10), Group III (Staph spp.) (n = 5), Group IV (Strep spp.) (n = 5). While electrical conductivity, somatic cell count (SCC), malondialdehyde (MDA) increased, miR-27a-3p and miR-223 upregulated and miR-125b downregulated in the CMT-positive group in Experiment I. SCC and MDA were higher in CMT-positive groups. miR-27a-3p and miR-223 upregulated in Groups III and IV. While miR-155 is upregulated, miR-125b downregulated in Group IV. Milk fat is positively correlated with miR-148a and miR-223. As miR-27a-3p positively correlated with SCC and MDA, miR-125b negatively correlated with electrical conductivity and SCC. miR-148a and MDA were positively correlated. miR-155 was correlated with fat-free dry matter, protein, lactose, and freezing point. miR-223 was positively correlated with SCC and miR-148a. Results particularly highlight miR-27a-3p and miR-223 as potential biomarkers in subclinical mastitis, especially those caused by Staph spp. and Strep spp., while miR-148a, miR-155, and miR-223 stand out in determining milk quality.

The presence of virulence factor genes downregulates uterine AQP3 and alters glutathione peroxidase activity and uterine histopathology in canine pyometra.

Present study was designed to evaluate the role of virulence factor genes (papG, cnf1 and hylA) in the pathogenesis of canine pyometra. Antimicrobial susceptibility test and detection of virulence genes were performed Escherichia coli (E. coli) detected in uterine swab samples. Animals were divided into two groups based on the presence (VF+, n:14) or absence (VF-, n:7) of the virulence factor genes papG, cnf1 and hylA. Blood and tissue glutathione peroxidase activity, uterine histopathologic analysis and AQP3, ESR1, PGR, OXTR gene expressions were determined in both groups. Statistical analyses were performed using Stata version 15.1. All E. coli isolates were susceptible to amikacin, whereas resistant to ampicillin, amoxicillin/clavulanic acid and lincomycin. None of the isolates were susceptible to cefotaxime. E. coli isolates had at least one virulence gene. The most prevalent gene was fimH (100%), followed by fyuA (95.8%), usp (83.3%), sfa (75%), cnf1 and hlyA (70.8%) genes. Blood GPx activity was greater in VF+ animals. On the other hand, uterine tissue GPx activity was lower in VF+ group compared to the control group. Expression levels of AQP3 were upregulated more than fivefold in VF-dogs compared to the control group. In addition, AQP3 expression levels were found approximately threefold higher in VF (-) than VF (+) group (p < .05). Varying degree of inflammation noted for all animals with pyometra, but the presence of bacteria noted only in VF+ animals. In conclusion, the presence of virulence factor genes does not play a role in the histopathological degree of inflammation, the presence of bacteria was found to vary. Serum GPx activity increased in VF+ animals. While the hormone receptor expressions were similar, AQP expression was upregulated in the absence of virulence factor genes.

Determination of expression patterns of miR-26a, and preimplantation factor levels for early pregnancy detection in nulliparous and multiparous cows.

For maximum productivity in a dairy farm, the earliest and the most accurate detection of pregnancy is essential. The aim of this study was to determine the efficacy of expression patterns of miR-26a, and serum Preimplantation Factor (PIF) levels for pregnancy diagnosis during the early pregnancy in nulliparous and multiparous cows. A total of 60 cows (30 nulliparous and 30 multiparous Holstein cows) were enrolled in the study. Blood samples were collected for miR-26a on days 8 and 16 (D8 and D16), and for the PIF on days 10 and 20 (D10 and D20) following insemination (D0). Pregnancies were determined by ultrasonography on the 28th day after insemination. Expression levels of miR-26a determined by qPCR. PIF levels were assessed by using commercial ELISA kits. All data were analyzed by using the MIXED procedure of SPSS. The expression levels of miR-26a were 6.64 folds higher on D16 in pregnant compared to non-pregnant multiparous cows (p < .05). On D8 and D16, miR-26a expression levels were found higher 13 folds in pregnant compared to non-pregnant nulliparous cows (p < .05). Additionally, miR-26a expressions were higher 5.42 folds (p < .05) on D8, 7.19 folds higher (p < .01) on D16 in pregnant nulliparous and multiparous cows, and were 6.30 folds higher (p < .001) on D8 and D16 according to non-pregnant animals. PIF levels were greater in pregnant animals (p < .05). Analyzing miR-26a on D8 might be considered as sufficient in nulliparous cows. Pregnancy detection in multiparous cows can be made on the 16th day with this method. Furthermore, PIF evaluations may be sufficient on D10 in multiparous cows. Besides, PIF levels and miR-26a expression levels might be used safely in field conditions and clinical applications.

Effects of propylene glycol used at different doses in Akkaraman lambs rations on metabolism-related parameters and liver gene and protein expression during different feeding periods.

This study aimed to investigate the metabolic effects of propylene glycol (PG) over 60, 90, and 120 days in lambs. Seventy-two weaned male lambs were allocated into three groups: control (Con), PG1.5 (1.5 mL/kg live weight0.75 ), and PG3 (3 mL/kg live weight0.75 ). Blood samples were collected at the beginning and slaughter days. Biochemical parameters (glucose, triglycerides, ALT, AST, LDH, BUN, and insulin) and gene and protein levels of peroxisome proliferator activated receptor gamma (PPARγ), diacylglycerol o-acyltransferase 1 (DGAT1), carbohydrate responsive element binding protein (ChREBP), and sterol regulatory element binding transcription factor 1c (SREBP-1c) in the liver were determined. Glucose in PG1.5 was increased on Day 60, while significant differences were observed in biochemical parameters except for insulin on the 60, 90, and 120 days. Biochemical parameters such as ALT, AST, LDH, and BUN increased over time, while triglycerides decreased. DGAT1 gene and protein levels were lower, while SREBP-1c and PPARγ were higher in PG groups on Day 60. While SREBP-1c was lower in PG1.5, ChREBP was higher in PG3 on Day 90. PPARγ, DGAT1, and ChREBP were upregulated in PG3 on Day 120. Positive correlations were found between proteins. The long-term use of PG in lambs did not have detrimental effects on metabolism. The study provides valuable insights into the molecular mechanisms underlying the metabolic effects of PG in lambs, shedding light on its potential applications in lamb production.

The thermographic monitoring in early pregnancy detection in Holstein cows and heifers.

This study aimed to conduct a comprehensive investigation to demonstrate early pregnancy detection using thermography in heifers and cows. A total of 60 heifers (n: 30) and cows (n: 30) were divided into two groups as pregnant (n: 15 heifers, n: 15 cows) and non-pregnant (n: 15 heifers, n: 15 cows) according to the day 28 of gestation. Thermographic images were taken from the vulvar and anal regions on alternate days from D0 to D20. Blood samples were collected to determine estrogen and progesterone concentrations. The mean temperature difference between the anal and vulvar regions (ΔT °C) was used in the statistical analyses. Based on the hormonal profiles, no abnormalities were observed for follicular waves or luteal profiles in heifers and cows. The ΔT °C values between heifers and cows and between days were statistically significant (P < 0.001). In thermographic analyses, the differences observed in other main effects and interactions of the group, sampling time, and pregnancy were not statistically significant (P > 0.05). In receiver operating characteristic (ROC) analyses, it was concluded that the ΔT °C value of ≤ 2.9 °C (100% Se - 61.9% Sp) was highly correlated with pregnancy diagnosis in cows on day six after artificial insemination (AI) (P < 0.001). In conclusion, it was determined that the clinical application of thermography can be used for the detection of pregnancy on day six after AI in cows. However, further studies are needed to determine heifers' thermographic characteristics and profiles.

CC-Chemokine Receptor-2 Expression in Osteoblasts Contributes to Cartilage and Bone Damage during Post-Traumatic Osteoarthritis.

In osteoarthritis (OA), bone changes are radiological hallmarks and are considered important for disease progression. The C-C chemokine receptor-2 (CCR2) has been shown to play an important role in bone physiology. In this study, we investigated whether Ccr2 osteoblast-specific inactivation at different times during post-traumatic OA (PTOA) progression improves joint structures, bone parameters, and pain. We used a tamoxifen-inducible Ccr2 inactivation in Collagen1α-expressing cells to obtain osteoblasts lacking Ccr2 (CCR2-Col1αKO). We stimulated PTOA changes in CCR2-Col1αKO and CCR2+/+ mice using the destabilization of the meniscus model (DMM), inducing recombination before or after DMM (early- vs. late-inactivation). Joint damage was evaluated at two, four, eight, and twelve weeks post-DMM using multiple scores: articular-cartilage structure (ACS), Safranin-O, histomorphometry, osteophyte size/maturity, subchondral bone thickness and synovial hyperplasia. Spontaneous and evoked pain were assessed for up to 20 weeks. We found that early osteoblast-Ccr2 inactivation delayed articular cartilage damage and matrix degeneration compared to CCR2+/+, as well as DMM-induced bone thickness. Osteophyte formation and maturation were only minimally affected. Late Collagen1α-Ccr2 deletion led to less evident improvements. Osteoblast-Ccr2 deletion also improved static measures of pain, while evoked pain did not change. Our study demonstrates that Ccr2 expression in osteoblasts contributes to PTOA disease progression and pain by affecting both cartilage and bone tissues.

The role of nutritional-immunological indices in estimating serum LPS and antioxidant enzyme activity and sepsis status in female dogs with pyometra caused by E. coli.

The aim of this study was to diagnose pyometra and related sepsis status using cost-effective nutritional-immunological indices, antioxidants, and toxin levels in dogs and to investigate the utility of the indices in predicting toxin and antioxidant status. A total of 29 dogs were enrolled into the present study. Among these, 9 female dogs in their diestrus stages, were allocated for elective ovariohysterectomy. The pyometra group was also separated into two subgroups as Sepsis (+) and Sepsis (-). Blood samples were collected into two tubes containing EDTA for hematological analysis; without anticoagulant for serum progesterone, LPS concentration, and antioxidant levels at the time of diagnosis. Bacteriological and tissue samples of the uterus were collected after the ovariohysterectomy. Antioxidant activity, progesterone, and toxin concentration were determined by using commercial ELISA kits. Statistical analyses were performed using Stata version 16.1 and MedCalc 16 statistical software. Receiver operating characteristics curves were used for the threshold for evaluating pyometra and sepsis status. Pairwise comparisons were carried out of the area under the curve (AUC) for thresholds of nutritional immunologic indices (hemoglobin, albumin, lymphocyte, platelet (HALP) score; prognostic nutritional index (PNI); Albumin hemoglobin index (AHI)), serum LPS and antioxidant activity. Linear regression model was used for the estimation of serum LPS and antioxidant activity by using indices. Mean serum progesterone, LPS concentrations, and Nitric Oxide (NO) production were greater, while serum superoxide dismutase (SOD), tissue SOD, and glutathione peroxidase (GPx) activities were lower in dogs with pyometra. All nutritional-immunologic indices were lower in pyometra cases. Nutritional-immunologic indices (AUC of HALP:0.759; PNI:0.981; AHI 0.994), NO (AUC: 0.787) and SOD (AUC: 0.784) levels were useful for pyometra diagnosis. AHI and LPS were useful for the determination of sepsis status with the AUC values of 0.850 and 0.740, respectively. While AHI was useful for the estimation of serum LPS and NO concentration (p < 0.001), PNI was useful for serum SOD concentration (p = 0.003). In conclusion, PNI, HALP and AHI can be used in the diagnosis of pyometra, however, only AHI and LPS levels can be used in the diagnosis of sepsis. SOD and NO can be used to determine pyometra but have no effect on determining sepsis status. Additionally, the estimation of the levels of serum LPS, NO, and SOD activities can be done using the AHI and PNI values.

Protective and Therapeutic Effects of Bovine Amniotic Fluids Collected in Different Trimesters on the Epidural Fibrosis After Experimental Laminectomy in Rats.

BACKGROUND: The aim of this study was to investigate the protective and therapeutic effects of bovine amniotic fluid (BAF) on the inhibition of epidural fibrosis (EF) after experimental laminectomy. METHODS: Forty female Sprague Dawley rats were used. The amniotic fluids were collected from each trimester of a pregnant cow. The rats were divided into 5 groups. Whereas no laminectomy was applied to the control group, animals in the sham group underwent laminectomy. Laminectomy was performed in the animals in other groups and the operation area was closed by dripping 1 mL of BAF collected in 3 trimesters of pregnancy. Animals were killed 28 days after the operation. RESULTS: Compared with control, VEGF gene expression levels were downregulated approximately 5-fold in BAF-2. Whereas IL-6 was upregulated approximately 8-fold in the sham, it was downregulated 5-fold and 3-fold in BAF-1 and BAF-2, respectively. There was downregulation in BAF-2 and BAF-3 in terms of CD105 gene expression levels. TGFß1 was upregulated approximately 2-fold in the sham group and downregulated in BAF-1 and BAF-2. Although histopathologic alterations including EF grade and fibroblast cell density were found to increase in the sham group, all BAF treatment decreased those of alterations. The highest CD105 immunoreactivity was detected in the sham group. All BAF treatment markedly aggravated fibrosis via decreasing CD105 immunoreactivity. In terms of grading parameters, almost the closest grades to the control were determined in the BAF-2. BAF collected in the second trimester is most effective in healing of scar tissue and preventing fibrosis via decreasing microvessel and fibroblast densities. CONCLUSIONS: The results indicate that BAF may be used as a potential protective agent to prevent EF.

Sustained inhibition of CC-chemokine receptor-2 via intraarticular deposition of polymeric microplates in post-traumatic osteoarthritis.

Posttraumatic osteoarthritis (PTOA) is mostly treated via corticosteroid administration, and total joint arthroplasty continues to be the sole effective intervention in severe conditions. To assess the therapeutic potential of CCR2 targeting in PTOA, we used biodegradable microplates (µPLs) to achieve a slow and sustained intraarticular release of the CCR2 inhibitor RS504393 into injured knees and followed joint damage during disease progression. RS504393-loaded µPLs (RS-µPLs) were fabricated via a template-replica molding technique. A mixture of poly(lactic-co-glycolic acid) (PLGA) and RS504393 was deposited into 20 × 10 µm (length × height) wells in a polyvinyl alcohol (PVA) square-patterned template. After physicochemical and toxicological characterizations, the RS504393 release profile from µPL was assessed in PBS buffer. C57BL/6 J male mice were subjected to destabilization of the medial meniscus (DMM)/sham surgery, and RS-µPLs (1 mg/kg) were administered intraarticularly 1 week postsurgery. Administrations were repeated at 4 and 7 weeks post-DMM. Drug free-µPLs (DF-µPLs) and saline injections were performed as controls. Mice were euthanized at 4 and 10 weeks post-DMM, corresponding to the early and severe PTOA stages, respectively. Knees were evaluated for cartilage structure score (ACS, H&E), matrix loss (safranin O score), osteophyte formation and maturation from cartilage to bone (cartilage quantification), and subchondral plate thickness. The RS-µPL architecture ensured the sustained release of CCR2 inhibitors over several weeks, with ~ 20% of RS504393 still available at 21 days. This prolonged release improved cartilage structure and reduced bone damage and synovial hyperplasia at both PTOA stages. Extracellular matrix loss was also attenuated, although with less efficacy. The results indicate that local sustained delivery is needed to optimize CCR2-targeted therapies.

The Matrix Metalloproteinase Inhibitor Batimastat Reduces Epidural Fibrosis After Laminectomy in Rats.

AIM: To investigate the efficacy of locally applied batimastat after laminectomy in preventing postoperative epidural fibrosis. MATERIAL AND METHODS: Thirty-two Wistar albino male rats weighing 200?250 g were used. The rats were assigned to four different groups (I-Control group, II-sham group, III-Laminectomy+Batimastat group, and IV-Laminectomy+SpongostanTM group). The rats were euthanized 28 days after surgery before TNF-?, IL6, IL-1?, IL10, TGF-?1, and MMP9 gene expression levels of tissue in the surgical area were determined with qPCR. TNF-?, IL6, and IL10 protein levels were also measured in both tissue and plasma. In addition, the surgical area was evaluated by histopathological and immunohistochemical methods. RESULTS: TNF-?, IL6, and IL-1? gene expression levels were higher in the batimastat group than in the control group. Whereas IL10 gene expression levels increased about two-fold in the sham and SpongostanTM groups, in the batimastat group, it was similar to that in the control group. TGF-?1 gene expression was three-fold higher in the sham group but was similar to that in the control group in both batimastat and SpongostanTM groups. MMP9 gene expression levels significantly decreased only in the batimastat group. In addition, fibrosis score, fibroblast cell count, inflammatory cell count, and CD105 expression decreased in the batimastat group relative to the control. CONCLUSION: Molecular and pathological examination results suggested that batimastat is an effective agent in reducing the occurrence of epidural fibrosis after laminectomy.

Transfer learning of an ensemble of DNNs for SSVEP BCI spellers without user-specific training.

Objective.Steady-state visually evoked potentials (SSVEPs), measured with electroencephalogram (EEG), yield decent information transfer rates (ITRs) in brain-computer interface (BCI) spellers. However, the current high performing SSVEP BCI spellers in the literature require an initial lengthy and tiring user-specific training for each new user for system adaptation, including data collection with EEG experiments, algorithm training and calibration (all are before the actual use of the system). This impedes the widespread use of BCIs. To ensure practicality, we propose a novel target identification method based on an ensemble of deep neural networks (DNNs), which does not require any sort of user-specific training.Approach.We exploit already-existing literature datasets from participants of previously conducted EEG experiments to train a global target identifier DNN first, which is then fine-tuned to each participant. We transfer this ensemble of fine-tuned DNNs to the new user instance, determine thekmost representative DNNs according to the participants' statistical similarities to the new user, and predict the target character through a weighted combination of the ensemble predictions.Main results.The proposed method significantly outperforms all the state-of-the-art alternatives for all stimulation durations in [0.2-1.0] s on two large-scale benchmark and BETA datasets, and achieves impressive 155.51 bits/min and 114.64 bits/min ITRs. Code is available for reproducibility:https://github.com/osmanberke/Ensemble-of-DNNs.Significance.Our Ensemble-DNN method has the potential to promote the practical widespread deployment of BCI spellers in daily lives as we provide the highest performance while enabling the immediate system use without any user-specific training.

TNF-alpha, IL-6, IL-10 and fatty acids in rheumatoid arthritis patients receiving cDMARD and bDMARD therapy.

OBJECTIVE: The present study aimed to examine the effects of cDMARD and bDMARD therapy on both gene expressions and protein levels of TNF-α, IL-6, IL-10 and fatty acid levels in patients with RA. METHOD: Plasma TNF-α, IL-6, and IL-10 levels were examined by the ELISA method, while TNF-α, IL-6, and IL-10 gene expression levels were examined by RT-qPCR, and fatty acid levels were examined by GC/MS. RESULTS: IL-10 gene expression levels significantly increased in RA patients receiving cDMARD treatment compared to those of the control group. Also, eicosadienoic acid, myristoleic acid and capric acid levels were significantly lower in the patient groups compared to those in the control group. CONCLUSION: The drugs used in the treatment of RA had no effect on the fatty acid levels whereas had effects on the mRNA and protein levels of the target cytokines.

Neural correlates of integration processes during dynamic face perception.

Integrating the spatiotemporal information acquired from the highly dynamic world around us is essential to navigate, reason, and decide properly. Although this is particularly important in a face-to-face conversation, very little research to date has specifically examined the neural correlates of temporal integration in dynamic face perception. Here we present statistically robust observations regarding the brain activations measured via electroencephalography (EEG) that are specific to the temporal integration. To that end, we generate videos of neutral faces of individuals and non-face objects, modulate the contrast of the even and odd frames at two specific frequencies ([Formula: see text] and [Formula: see text]) in an interlaced manner, and measure the steady-state visual evoked potential as participants view the videos. Then, we analyze the intermodulation components (IMs: ([Formula: see text]), a linear combination of the fundamentals with integer multipliers) that consequently reflect the nonlinear processing and indicate temporal integration by design. We show that electrodes around the medial temporal, inferior, and medial frontal areas respond strongly and selectively when viewing dynamic faces, which manifests the essential processes underlying our ability to perceive and understand our social world. The generation of IMs is only possible if even and odd frames are processed in succession and integrated temporally, therefore, the strong IMs in our frequency spectrum analysis show that the time between frames (1/60 s) is sufficient for temporal integration.

A Deep Neural Network for SSVEP-Based Brain-Computer Interfaces.

OBJECTIVE: Target identification in brain-computer interface (BCI) spellers refers to the electroencephalogram (EEG) classification for predicting the target character that the subject intends to spell. When the visual stimulus of each character is tagged with a distinct frequency, the EEG records steady-state visually evoked potentials (SSVEP) whose spectrum is dominated by the harmonics of the target frequency. In this setting, we address the target identification and propose a novel deep neural network (DNN) architecture. METHOD: The proposed DNN processes the multi-channel SSVEP with convolutions across the sub-bands of harmonics, channels, time, and classifies at the fully connected layer. We test with two publicly available large scale (the benchmark and BETA) datasets consisting of in total 105 subjects with 40 characters. Our first stage training learns a global model by exploiting the statistical commonalities among all subjects, and the second stage fine tunes to each subject separately by exploiting the individualities. RESULTS: Our DNN achieves impressive information transfer rates (ITRs) on both datasets, 265.23 bits/min and 196.59 bits/min, respectively, with only 0.4 seconds of stimulation. The code is available for reproducibility at https://github.com/osmanberke/Deep-SSVEP-BCI. CONCLUSION: The presented DNN strongly outperforms the state-of-the-art techniques as our accuracy and ITR rates are the highest ever reported performance results on these datasets. SIGNIFICANCE: Due to its unprecedentedly high speller ITRs and flawless applicability to general SSVEP systems, our technique has great potential in various biomedical engineering settings of BCIs such as communication, rehabilitation and control.

Combination of trehalose and low boron in presence of decreased glycerol improves post-thawed ram sperm parameters: A model study in boron research.

BACKGROUND: Sperm cryopreservation has been widely used in the field of reproductive biotechnology. It applies to certain males of economic and scientific values, including livestock breeds or endangered animal species. The development of a semen extender with a low cryoprotectant concentration and an appropriate amount of trehalose and boron can prevent the deterioration of sperm parameters. OBJECTIVE: The main goal of this study is to establish a suitable ram extender model, by examining different combinations of high (5%) and low (3%) glycerol concentrations (to reduce its toxic effects on sperm freezing), a fixed amount of trehalose and an increased dose of boron to prevent the deterioration of sperm parameters, and investigate the levels of gene expressions. MATERIALS AND METHODS: The Merino ram ejaculates were collected. The collected ejaculates providing the defined criteria were pooled. The pooled ejaculates were divided into eight aliquots and diluted with the Tris extender including different combinations of glycerol (5% and 3%) and boron (0.25, 0.5, and 1 mm) concentrations and a fixed amount of trehalose, then frozen. After freeze-thawing process, sperm motility, mitochondrial membrane activity, plasma membrane integrity, acrosomal membrane integrity, DNA damage (single cell gel electrophoresis (COMET) and TUNEL assays) as well as NAD(P)H quinone oxyreductase (NQO1), glutamate-cycteine ligase (GCLC), and glutathione S-transferase (GSTP1) for molecular mechanisms of sperm cell response to oxidative stress were assessed for different extender groups following freeze-thawing process: 5% glycerol + 0 mm boron (G5B0.00), 5% glycerol + 0.25 mm boron (G5B0.25), 5% glycerol + 0.5 mm boron (G5B0.50), 5% glycerol + 1 mm boron (G5B1.00), 3% glycerol + 0 mm boron (G3B.00), 3% glycerol + 0.25 mm boron (G3B0.25), 3% glycerol + 0.5 mm boron (G3B0.50), and 3% glycerol + 1 mm boron (G3B1.00). RESULTS: G3B0.25 presented higher percentages of subjective motility, mitochondrial activity, and viability of spermatozoa comparing with G5B0.00 and groups with boron. Supplementation of 0.25 mm boron with and without trehalose (G3B0.25 and G5B0.25) showed higher acrosome integrity, compared with G5B0.00, G5B1.00, G3B0.50, and G3B1.00. For TUNEL analysis, G3B1.00 showed the highest DNA integrity among the experimental groups which was statistically significant only with G5B0.50 (p < 0.05). The mRNA levels of NQO1 were significantly decreased in G5B1.00, G3B0.50, and G3B1.00, when compared to G5B0.00. In comparison with G5B0.00, supplementation of 1 mm boron with and without trehalose had significantly lower expression of GCLC. The level of GSTP1 gene was significantly lower (approximately threefold) in G3B1.00, compared to G5B0.00 (p < 0.05). DISCUSSION AND CONCLUSION: It can be assumed that the increase of the boron concentration in the extender may have important adverse effects on sperm parameters and antioxidant gene expression after thawing. The results obtained from this study will help to understand the toxicity limits of boron and eliminate the toxicity of glycerol in studies of gametes and tissue freezing. Therefore, it can be concluded that the use of sufficient boron can decrease cryodamages of cryopreservation of mammalian spermatozoa as well tissue engineering.

Evaluation of psychosocial functioning in the acute treatment term of major depressive disorder: A 16-week multi-centered follow-up study.

OBJECTIVE: Major depressive disorder is the leading cause of non-fatal burden, and disability in adulthood. Even though depression is well-treated in the acute term,psychosocial functioning does not get back to the premorbid level most of the time. In this present study, it is aimed to evaluate the outcome of the acute term treatment of major depressive disorder in terms of psychosocial functioning. METHODS: The study is an open-label, observational, multi-center follow-up study for four months of patients with major depressive disorder according to DSM-5. Patients were evaluated with Montgomery Asberg Depression Rating Scale (MADRS), Sheehan Disability Scale (SDS) and Short Form-36 (SF-36) at the beginning, and at the 2., 4., 8., 12. and 16.weeks. RESULTS: 100 patients were invited to the study and 56 patients completed the study.As a result of the treatment, the mean MADRS and SDS scores decreased significantly. All domains of SF-36 were improved significantly with the treatment. Unfortunately patients suffering from MDD could not reach the normative data,especially on the domains of social functioning, role emotional, pain, and general health perception. Treatment outcomes show that SNRI users presented higher scores on the domains of pain and physical functioning. However SSRI users showed better outcomes on the domains of mental health and vitality. CONCLUSION: Our research corroborated that even patients gain symptomatic remission in MDD treatment, psychosocial dysfunction persists. It is also concluded that different antidepressant options may act differently on treatment outcomes.