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The primary objective of this manuscript is to examine the online assessment and exam security procedures during the pandemic, with a particular focus on higher education. In this context, the study investigates the measures employed by instructors, the challenges they encountered, and the strategies they employed to overcome these challenges in a higher education institution. To this end, a case study was conducted, employing a mixed research approach and utilizing both quantitative and qualitative data obtained through a questionnaire. The study group consisted of 163 instructors who provided distance education during the pandemic and volunteered to participate in the study. The findings have shown that the measures were largely contingent on the capabilities of the Learning Management System (LMS) in use. It was emphasized that students should be informed before the exam, that the appropriate exam duration and technical infrastructure conditions should be determined, and that accessibility should be ensured. The results highlight the necessity for the development of policies to address ethical concerns and the suggestion of standardizing the use of cameras in online exams. For more generalized results and recommendations, longer-term studies can focus on synthesizing the experiences and opinions of different stakeholders.

# Background The February 2023 earthquakes in Turkey and Syria exposed significant gaps in healthcare information systems, which severely hampered communication, coordination, and the overall public health response. These disruptions were primarily due to the lack of real-time, accessible data on healthcare facilities. # Methods In response, an interactive Geographic Information System (GIS) tool, coupled with an integrated WhatsApp chatbot, was developed under the platform Afetsaglikharitasi.org. This system enabled real-time mapping and updates on the status of healthcare services, even in areas with limited internet connectivity, facilitating more efficient resource coordination during the disaster response. # Results By March 30, 2023, the disaster health map included data from 537 health centers and had reached over 800,000 individuals via social media platforms such as Instagram, Facebook, and Twitter. The platform attracted over 3,500 unique users, with most accessing it via mobile devices to locate healthcare services. Additionally, shortcomings in the Turkey National Disaster Response Plan (Türkiye Afet Müdahale Planı -- TAMP) were identified, particularly the lack of integration of digital health technologies, which hindered resource allocation during the earthquake response and underscored the need for their inclusion in disaster management strategies. # Conclusions This study demonstrates the effectiveness of digital health tools in enhancing disaster response and underscores the importance of integrating user-centered, deployable technologies to improve healthcare delivery in emergency settings.

The topic of privacy-preserving collaborative filtering is gaining more and more attention. Nevertheless, privacy-preserving collaborative filtering techniques are vulnerable to shilling or profile injection assaults. Hence, it is crucial to identify counterfeit profiles in order to achieve total success. Various techniques have been devised to identify and prevent intrusion patterns from infiltrating the system. Nevertheless, these strategies are specifically designed for collaborative filtering algorithms that do not prioritize privacy. There is a scarcity of research on identifying shilling attacks in recommender systems that prioritize privacy. This work presents a novel technique for identifying shilling assaults in privacy-preserving collaborative filtering systems. We employ an ant colony clustering detection method to effectively identify and eliminate fake profiles that are created by six widely recognized shilling attacks on compromised data. The objective of the study is to categorize the fraudulent profiles into a specific cluster and separate this cluster from the system. Empirical experiments are conducted with actual data. The empirical findings demonstrate that the strategy derived from the study effectively eliminates fraudulent profiles in privacy-preserving collaborative filtering.

In this study, a new bitter chocolate with functional properties was produced by using different tempering temperatures with different ratios of wolfberry addition and physicochemical, antioxidant, textural and sensory properties of these chocolates were determined. It was observed that fruit ratios on bitter chocolate had a statistically significant (P

Abstract The role of high mobility group box 1 (HMGB1) in inflammation is well characterized in the immune system and in response to tissue injury. More recently, HMGB1 was also shown to initiate an “inflammatory signaling cascade” in the brain parenchyma after a mild and brief disturbance, such as cortical spreading depolarization (CSD), leading to headache. Despite substantial evidence implying a role for inflammatory signaling in prevalent neuropsychiatric disorders such as migraine and depression, how HMGB1 is released from healthy neurons and how inflammatory signaling is initiated in the absence of apparent cell injury are not well characterized. We triggered a single cortical spreading depolarization by optogenetic stimulation or pinprick in naïve Swiss albino or transgenic Thy1-ChR2-YFP and hGFAP-GFP adult mice. We evaluated HMGB1 release in brain tissue sections prepared from these mice by immunofluorescent labeling and immunoelectron microscopy. EzColocalization and Costes thresholding algorithms were used to assess the colocalization of small extracellular vesicles (sEVs) carrying HMGB1 with astrocyte or microglia processes. sEVs were also isolated from the brain after CSD, and neuron-derived sEVs were captured by CD171 (L1CAM). sEVs were characterized with flow cytometry, scanning electron microscopy, nanoparticle tracking analysis, and Western blotting. We found that HMGB1 is released mainly within sEVs from the soma of stressed neurons, which are taken up by surrounding astrocyte processes. This creates conditions for selective communication between neurons and astrocytes bypassing microglia, as evidenced by activation of the proinflammatory transcription factor NF-ĸB p65 in astrocytes but not in microglia. Transmission immunoelectron microscopy data illustrated that HMGB1 was incorporated into sEVs through endosomal mechanisms. In conclusion, proinflammatory mediators released within sEVs can induce cell-specific inflammatory signaling in the brain without activating transmembrane receptors on other cells and causing overt inflammation.

This study explored elementary students’ reasoning about the life cycles of various organisms, including insects and amphibians. The study took place in a private school in Lebanon with 24 fifth-grade students. Students participated in a life cycle unit with pre and post-written assessments about what they learned and interviews to help determine their reasoning about life cycles. Using our findings, we suggest a learning progression (LP) approach to guide students over time in their learning about life cycles and their importance for species persistence within an ecosystem. Two LPs were developed from this study: Reasoning about the cyclic nature of life and comparison of life cycle stages. Overall, students improved their understanding of the cyclical nature of life, but comparing organisms’ structures, stages, and life cycles proved to be more challenging. These LPs have direct implications for elementary instruction about life cycles, organisms, and species.

Homeostatic restoration of an inflammatory response requires quenching of the immune system after pathogen threats vanish. A continued assault orchestrated by host defense results in tissue destruction or autoimmunity. A151 is the epitome of synthetic oligodeoxynucleotides (ODNs) that curb the immune response by a subset of white corpuscles through repetitive telomere-derived TTAGGG sequences. Currently, the genuine effect of A151 on the immune cell transcriptome remains unknown. Here, we leveraged an integrative approach where weighted gene co-expression network analysis (WGCNA), differential gene expression analysis, and gene set enrichment analysis (GSEA) of our in-house microarray datasets aided our understanding of how A151 ODN suppresses the immune response in mouse splenocytes. Our bioinformatics results, together with experimental validations, indicated that A151 ODN acts on components of integrin complexes, Itgam and Itga6, to interfere with immune cell adhesion and thereby suppresses the immune response in mice. Moreover, independent lines of evidence in this work converged on the observation that cell adhesion by integrin complexes serves as a focal point for cellular response to A151 ODN treatment in immune cells. Taken together, the outcome of this study sheds light on the molecular basis of immune suppression by a clinically useful DNA-based therapeutic agent.

Abstract Recombinant protein-based SARS-CoV-2 vaccines are needed to fill the vaccine equity gap. Because protein-subunit based vaccines are easier and cheaper to produce and do not require special storage/transportation conditions, they are suitable for low-/middle-income countries. Here, we report our vaccine development studies with the receptor binding domain of the SARS-CoV-2 Delta Plus strain (RBD-DP) which caused increased hospitalizations compared to other variants. First, we expressed RBD-DP in the Pichia pastoris yeast system and upscaled it to a 5-L fermenter for production. After three-step purification, we obtained RBD-DP with > 95% purity from a protein yield of > 1 g/L of supernatant. Several biophysical and biochemical characterizations were performed to confirm its identity, stability, and functionality. Then, it was formulated in different contents with Alum and CpG for mice immunization. After three doses of immunization, IgG titers from sera reached to > 106 and most importantly it showed high T-cell responses which are required for an effective vaccine to prevent severe COVID-19 disease. A live neutralization test was performed with both the Wuhan strain (B.1.1.7) and Delta strain (B.1.617.2) and it showed high neutralization antibody content for both strains. A challenge study with SARS-CoV-2 infected K18-hACE2 transgenic mice showed good immunoprotective activity with no viruses in the lungs and no lung inflammation for all immunized mice.

Introduction: Non-healing wounds remain a major burden due to the lack of effective treatments. Mesenchymal stem cell-derived exosomes (MSC-Exo) have emerged as therapeutic options given their pro-regenerative and immunomodulatory features. Still, little is known on the exact mechanisms mediated by MSC-Exo. Importantly, modulation of their efficacy through 3D-physiologic cultures together with loading strategies continues underexplored. Objectives: To uncover the MSC-Exo-mediated mechanism via proteomic analyses, and to use 3D-culture and loading technologies to expand MSC-Exo efficacy for cutaneous wound healing. Methods: MSC-Exo were produced in either 3D or 2D cultures (Exo3D/Exo2D) and loaded with an exogenous immunosuppressive oligodeoxynucleotide (A151 ODN). Both, loaded and naïve exosomes were characterised regarding size, morphology and the presence of specific protein markers; while IPA analyses enabled to correlate their protein content with the effects observed in vitro and in vivo. The Exo3D/Exo2D regenerative potential was evaluated in vitro by assessing keratinocyte and fibroblast mitogenicity, motogenicity, and cytokine secretion as well as using an in vivo wound splinting model. Accordingly, the modulation of inflammatory and immune responses by A151-loaded Exo3D/Exo2D was also assessed. Results: Exo3D stimulated mitogenically and motogenically keratinocytes and fibroblasts in vitro, with upregulation of IL-1α and VEGF-α or increased secretion of TGF-β, TNF-α and IL-10. In vivo, Exo3D reduced the granulation tissue area and promoted complete re-epithelization of the wound. These observations were sustained by the proteomic profiling of the Exo3D cargo that identified wound healing-related proteins, such as TGF-β, ITGA1-3/5, IL-6, CDC151, S100A10 and Wnt5α. Moreover, when loaded with A151 ODN, Exo3D differentially mediated wound healing-related trophic factors reducing the systemic levels of IL-6 and TNF-α at the late stage of wound healing in vivo. Conclusion: Our results support the potential of A151-loaded Exo3D for the treatment of chronic wounds by promoting skin regeneration, while modulating the systemic levels of the pro-inflammatory cytokines.

Persistent diabetic complications despite controlled blood glucose levels, known as hyperglycemic memory, remain a poorly understood phenomenon in diabetic kidney disease. Here the authors identify senescence-associated gene p21 as a regulator of hyperglycemic memory, the suppression of which improves hyperglycemic memory and renal function.

Mesenchymal stem cell-derived exosomes regulate cell migration, proliferation, differentiation, and synthesis of the extracellular matrix, giving great potential for the treatment of different diseases. The ultracentrifugation method is the gold standard method for exosome isolation due to the simple protocol, and high yield, but presents low purity and requires specialized equipment. Amelioration of technical optimization is required for quick and reliable confinement of exosomes to translate them to the clinic as cell therapeutics In this study, we hypothesized that magnetically activated cell sorting may provide, an effective, reliable, and rapid tool for exosome isolation when compared to ultracentrifugation. We, therefore, aimed to compare the efficiency of magnetically activated cell sorting and ultracentrifugation for human mesenchymal stem cell-derived exosome isolation from culture media by protein quantification, surface biomarker, size, number, and morphological analysis. Magnetically activated cell sorting provided a higher purity and amount of exosomes that carry visible magnetic beads when compared to ultracentrifugation. The particle number of the magnetically activated cell sorting group was higher than the ultracentrifugation. In conclusion, magnetically activated cell sorting presents a quick, and reliable method to collect and present human mesenchymal stem cell exosomes to clinics at high purity for potential cellular therapeutic approaches. The novel isolation and purification method may be extended to different clinical protocols using different autogenic or allogeneic cell sources.

Leishmania parasites harbor a unique network of circular DNA known as kinetoplast DNA (kDNA). The role of kDNA in leishmania infections is poorly understood. Herein, we show that kDNA delivery to the cytosol of Leishmania major infected THP-1 macrophages provoked increased parasite loads when compared to untreated cells, hinting at the involvement of cytosolic DNA sensors in facilitating parasite evasion from the immune system. Parasite proliferation was significantly hindered in cGAS- STING- and TBK-1 knockout THP-1 macrophages when compared to wild type cells. Nanostring nCounter gene expression analysis on L. major infected wild type versus knockout cells revealed that some of the most upregulated genes including, Granulysin (GNLY), Chitotriosidase-1 (CHIT1), Sialomucin core protein 24 (CD164), SLAM Family Member 7 (SLAMF7), insulin-like growth factor receptor 2 (IGF2R) and apolipoprotein E (APOE) were identical in infected cGAS and TBK1 knockout cells, implying their involvement in parasite control. Amlexanox treatment (a TBK1 inhibitor) of L. major infected wild type cells inhibited both the percentage and the parasite load of infected THP-1 cells and delayed footpad swelling in parasite infected mice. Collectively, these results suggest that leishmania parasites might hijack the cGAS-STING-TBK1 signaling pathway to their own advantage and the TBK1 inhibitor amlexanox could be of interest as a candidate drug in treatment of cutaneous leishmaniasis.

Trade is a significant parameter that may impact environment positively or negatively. However, there is no consensus on this issue among the researchers. It seems likely that tradable products will affect the environmental quality level. However, this requires the separation of the international trade basket. Thus, this research asks whether trade in non-green products affects the level of environmental degradation in the 25 European Union (EU) member states? To answer this question, we develop an index of trade openness in non-green products and empirically investigate whether this index influences the ecological footprint. Non-green trade openness index represents the ratio of the total export and import of non-green products in a country’s international trade basket to that country’s Gross Domestic Product. Advanced panel estimation techniques are employed for a sample of 25 EU countries over the period between 2003 and 2016. The core finding–supporting the Pollution Haven Hypothesis–is that non-green trade openness reduces environmental degradation. We discuss several implications of this result for recent environmental policies, particularly for the EU climate policy.

ABSTRACT BACKGROUND: The results from sphincteroplasty may worsen over time. Reseparation of the rectum and vagina/scrotum in conjunction with sphincteroplasty achieves good results. Improving the surgical effect of sphincteroplasty through perineal body reconstruction is crucial. OBJECTIVE: To evaluate the long-term results from anterior sphincteroplasty and perineal body reconstruction (modified sphincteroplasty) among patients with traumatic sphincter injury. DESIGN AND SETTING: Retrospective study among patients who underwent modified sphincteroplasty in a university hospital between January 2006 and December 2018. Fifty patients were evaluated in detail. METHODS: The following variables were evaluated: gender, age, additional disease status, time interval between trauma and surgery, surgical technique, duration of hospitalization, follow-up period after surgery, manometric values, electromyography results, magnetic resonance imaging scans, Wexner scores, satisfaction levels with surgery and surgical outcomes. RESULTS: The patients’ mean age was 44.6 ± 15.1 years. The median follow-up period was 62 months (range, 12-118). The mean Wexner scores preoperatively, postoperatively in first month (M1S) and at the time of this report (AAS) were 15.5 ± 3.2, 1.9 ± 3.15 and 3.9 ± 5.3, respectively. Although improvements in the patients’ mean Wexner scores became impaired over time, the postoperative Wexner scores were still significantly better than the preoperative Wexner scores (P = 0.001). CONCLUSION: Good or excellent results were obtained surgically among patients with traumatic sphincter injury. Performing perineal body reconstruction in addition to sphincteroplasty can provide better long-term continence. Surgical outcomes were found to be better, especially among patients younger than 50 years of age and among patients who underwent surgery within the first five years after trauma.

Global Mobile Communications (GSMs) systems have been developed very rapidly over the past decades. Mobile phone base stations are located almost everywhere nowadays. However, there is a deep concern about the health associated risks of electromagnetic radiation of GSM signals. Unwanted interference between GSM systems and electronic devices is another important issue to be considered. Transforming building surfaces to frequency selective filters is an efficient solution approach to decrease RF exposure levels inside the buildings and to prevent unwanted interference. As a solution approach, single-layer frequency selective surface (FSS) geometry is proposed in this work, which reflects 900 MHz, 1800 MHz and 2100 MHz GSM frequency bands. 1800 MHz and 2100 MHz GSM bands are considered as a single frequency band in this work since they are very close to each other. Ansoft HFSS software is used for simulation, design, and optimization purposes. The equivalent circuit model is also utilized at the design and optimization stages. Achieved results show that proposed FSS element geometry has a stable frequency response up to 60 degrees of incidence angle with minimum of 10 dB attenuation.

Introduction: Otosclerosis is an idiopathic disease characterized by new bone formation in foci of the human otic capsule. It is more common in Caucasian populations; affecting females twice as often as males. Its etiopathogenesis has not yet been fully elucidated. Objective: The aim of this study was to investigate the relationship between otosclerosis and white blood cell and thrombocyte counts, mean platelet volume, neutrophil lymphocyte ratio, and the platelet lymphocyte ratio. Methods: This retrospective case-control study was conducted in the outpatient clinic Mustafa Kemal University, in the department of otolaryngology, between 2015 and 2018. A total of 30 patients with an established diagnosis of otosclerosis were compared to a control group of 30 healthy subjects, matched for age, gender and body mass index. The white blood cell, thrombocyte, mean platelet volume, neutrophil lymphocyte ratio and platelet lymphocyte ratio values were calculated for all participants. Results: There was no statistically significant difference between the groups with respect to age, gender, or body mass index, or for the mean neutrophil lymphocyte ratio, platelet lymphocyte ratio, white blood cell, or thrombocyte values (p > 0.05). A statistically significant difference was determined between the groups for the mean platelet volume values. The mean platelet volume values were lower in the otosclerotic patients (p = 0.047). Conclusion: These results show that neutrophil lymphocyte ratio, platelet lymphocyte ratio, white blood cell and thrombocytes should not be used to predict otosclerosis, but suggest that mean platelet volume may be a negative predictive marker. Resumo: Introdução: A otosclerose é uma doença idiopática caracterizada por neoformação óssea em focos da cápsula ótica humana. É mais comum em populações caucasianas, afeta o sexo feminino numa taxa 2 vezes maior do que o masculino. A etiopatogenia ainda não foi totalmente elucidada. Objetivo: Investigar a relação entre otosclerose e taxa de glóbulos brancos, plaquetas, volume plaquetário médio, relação neutrófilos-linfócitos e relação plaquetas-linfócitos. Método: Estudo retrospectivo de caso-controle feito no ambulatório da Mustafa Kemal University, Departamento de Otorrinolaringologia, entre 2015 e 2018. Foram comparados 30 pacientes com diagnóstico estabelecido de otosclerose com um grupo controle de 30 indivíduos saudáveis, pareados por idade, sexo e índice de massa corpórea. Os valores de glóbulos brancos, plaquetas, volume plaquetário médio, relação neutrófilos-linfócitos e relação plaquetas/linfócitos foram calculados para todos os participantes. Resultados: Não houve diferença estatisticamente significante entre os grupos em relação a idade, sexo ou índice de massa corpórea, ou em relação aos valores médios de relação neutrófilos-linfócitos, relação plaquetas/linfócitos, valores de glóbulos brancos e plaquetas (p > 0,05). Uma diferença estatisticamente significante foi observada entre os grupos em termos de valores médios de volume plaquetário médio. Os valores de volume plaquetário médio foram menores nos pacientes com otosclerose (p = 0,047). Conclusão: A relação plaquetas/linfócitos, a relação plaquetas/linfócitos, os valores de glóbulos brancos e plaquetas não podem ser usados para predizer a otosclerose, mas sugerem que o volume plaquetário médio possa ser um marcador preditivo negativo.

ObjectiveAtherosclerosis, the main pathology underlying cardiovascular diseases is accelerated in diabetic patients. Genetic mouse models require breeding efforts which are time-consuming and costly. Our aim was to establish a new nongenetic model of inducible metabolic risk factors that mimics hyperlipidemia, hyperglycemia, or both and allows the detection of phenotypic differences dependent on the metabolic stressor(s).Methods and ResultsWild-type mice were injected with gain-of-function PCSK9D377Y (proprotein convertase subtilisin/kexin type 9) mutant adeno-associated viral particles (AAV) and streptozotocin and fed either a high-fat diet (HFD) for 12 or 20 weeks or a high-cholesterol/high-fat diet (Paigen diet, PD) for 8 weeks. To evaluate atherosclerosis, two different vascular sites (aortic sinus and the truncus of the brachiocephalic artery) were examined in the mice. Combined hyperlipidemic and hyperglycemic (HGHCi) mice fed a HFD or PD displayed characteristic features of aggravated atherosclerosis when compared to hyperlipidemia (HCi HFD or PD) mice alone. Atherosclerotic plaques of HGHCi HFD animals were larger, showed a less stable phenotype (measured by the increased necrotic core area, reduced fibrous cap thickness, and less α-SMA-positive area) and had more inflammation (increased plasma IL-1β level, aortic pro-inflammatory gene expression, and MOMA-2-positive cells in the BCA) after 20 weeks of HFD. Differences between the HGHCi and HCi HFD models were confirmed using RNA-seq analysis of aortic tissue, revealing that significantly more genes were dysregulated in mice with combined hyperlipidemia and hyperglycemia than in the hyperlipidemia-only group. The HGHCi-associated genes were related to pathways regulating inflammation (increased Cd68, iNos, and Tnfa expression) and extracellular matrix degradation (Adamts4 and Mmp14). When comparing HFD with PD, the PD aggravated atherosclerosis to a greater extent in mice and showed plaque formation after 8 weeks. Hyperlipidemic and hyperglycemic mice fed a PD (HGHCi PD) showed less collagen (Sirius red) and increased inflammation (CD68-positive cells) within aortic plaques than hyperlipidemic mice (HCi PD). HGHCi-PD mice represent a directly inducible hyperglycemic atherosclerosis model compared with HFD-fed mice, in which atherosclerosis is severe by 8 weeks.ConclusionWe established a nongenetically inducible mouse model allowing comparative analyses of atherosclerosis in HCi and HGHCi conditions and its modification by diet, allowing analyses of multiple metabolic hits in mice.

Colorectal cancer (CRC); is the most common malignancy in the gastrointestinal tract. CRC is associated with significant morbidity and mortality in the worldwide. CRC is the third most common cancer-related death in both men and women globally. The overall 5-year survival rate is 50% last decade (1975). Currently this rate is over 75-80%. In this case; early diagnosis, prevention and effective treatment methods were the main factors. Nowadays, Genetic Analysis test, Fecal Occult Blood testing and colonoscopy methods are used in screening. Genetic Analysis testing is the best method for the lead time. In addition, polypectomy was performed in precarious patients and was classified as preventable disease.

The literature is considerably rich about engagement and academic achievement in the context of open and distance learning. However, there is limited research that investigates these variables with large scale participants. In this regard, the aim of this research was to investigate causal correlations between e-learning engagement time and academic achievement of open and distance learners according to course subject, dropout, and bounce rate variables. The participants of this study were 323,264 open and distance learners from Anadolu University, Turkey. Throughout this research, open and distance learners’ engagement time levels and their academic achievements are compared. Academic achievement was found to increase significantly when learners engaged more with e-learning materials.

Liver cell transplantation is a powerful alternative to orthotopic cell transplantation in the treatment of liver failures. Recently, considerable effort is being channeled to understand the nature and kinetics of directing stem cells to effectively accumulate at the regenerating liver site. Mesenchymal stem cells are one of the promising cell sources modulating liver regeneration process. Present was designed to study how mesenchymal stem cells might modulate liver immune behaviors by changing Toll-like receptor (TLR) expression and increase regenerative potential during liver regeneration in rats. Normal and partially hepatectomized rats were treated with mesenchymal stem cells isolated and expanded from rat bone marrows. Accumulation of mesenchymal stem cells was confirmed by Real Time-Polymerase Chain Reaction (RT-PCR), Fluorescence-Activated Cell Sorting (FACS), and Immunofluorescence Staining (IFS). Student's t-test analysis was used to evaluate the significance of differences between sham and partially hepatectomized rat groups. Our results showed that mesenchymal stem cells expressed several TLRs, and their accumulation during regeneration was depended on the timing of injury. Mesenchymal stem cells isolated from bone marrow of normal rats were observed at the injured liver 3 days after the injection. There were no labeled mesenchymal stem cells in the liver sections of the uninjured animals. Mesenchymal stem cell administration significantly altered the expression of TLR2, 3 and 9 while retaining their migration potential to regenerating liver. Our findings implicated that mesenchymal stem cell administration during liver regeneration modulate the immune response through changing the expression of the TLRs in the remaining liver parts into which the cells are recruited or infused. This alteration may contribute to the regeneration process following partial hepatectomy.

Graft-vs.-host disease is a complication of allogenic hematopoietic stem cell transplantation, and is associated with endothelial dysfunction. Here the authors show that activated protein C signals via PAR2/PAR3 to expand Treg cells, mitigating the disease in mice.

An extremely rare association of H-type anorectal malformation (ARM) and H-type tracheoesophageal fistula case is presented with literature review of the previously reported cases. Characteristics of the most commonly reported male H-type ARM patients are discussed. The proposed embryology and options for repair are discussed as well. Most surgical approaches have satisfactory results leaving approach selection to the surgeon experience and comfortability.

Vaccines are the most effective medical intervention due to their continual success in preventing infections and improving mortality worldwide. Early vaccines were developed empirically however, rational design of vaccines can allow us to optimise their efficacy, by tailoring the immune response. Establishing the immune correlates of protection greatly informs the rational design of vaccines. This facilitates the selection of the best vaccine antigens and the most appropriate vaccine adjuvant to generate optimal memory immune T cell and B cell responses. This review outlines the range of vaccine types that are currently authorised and those under development. We outline the optimal immunological correlates of protection that can be targeted. Finally we review approaches to rational antigen selection and rational vaccine adjuvant design. Harnessing current knowledge on protective immune responses in combination with critical vaccine components is imperative to the prevention of future life-threatening diseases.

In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.

Behçet’s disease (BD) activity is characterised by sustained, over-exuberant immune activation, yet the underlying mechanisms leading to active BD state are poorly defined. Herein, we show that the human cathelicidin derived antimicrobial peptide LL37 associates with and directs plasma extracellular vesicles (EV) to immune cells, thereby leading to enhanced immune activation aggravating BD pathology. Notably, disease activity was correlated with elevated levels of circulating LL37 and EV plasma concentration. Stimulation of healthy PBMC with active BD patient EVs induced heightened IL1β, IFNα, IL6 and IP10 secretion compared to healthy and inactive BD EVs. Remarkably, when mixed with LL37, healthy plasma-EVs triggered a robust immune activation replicating the pathology inducing properties of BD EVs. The findings of this study could be of clinical interest in the management of BD, implicating LL37/EV association as one of the major contributors of BD pathogenesis. Abbreviations: BD: Behçet’s disease; EV: extracellular vesicle; BB: binding buffer; AnV: annexin V; autologEV: autologous extracellular vesicles; alloEV: allogeneic extracellular vesicles

Bu olgu raporunda büyüme ve gelişimi tamamlanmış Sınıf III maloklüzyona sahip bir hastanın ortodontik ve cerrahi tedavisi sunulmuştur. 17 yaşındaki bayan hasta, alt çene ileriliği, üst çene geriliği ile karakterize iskeletsel ve dental Sınıf III maloklüzyon özelliklerini taşımaktaydı. Hastanın 14 ay süren cerrahi öncesi ortodontik tedavisinde kapaklı braketler tercih edilmiştir. Ortodontik tedaviyi takiben alt ve üst çene arasındaki iskeletsel uyumsuzluğunu düzeltmek için her iki çeneye de cerrahi müdahale yapılmıştır. Cerrahi sonrası yapılan ortodontik tedavi ile dişler uygun konumlarına getirilerek oklüzyon düzeltilmiş ve diş çekimi yapılmaksızın iskeletsel ve dişsel Sınıf I ilişki ile ideal bir yumuşak doku profili elde edilmiştir. İskeletsel Sınıf III maloklüzyonların ortodonti ve ortognatik cerrahi kombinasyonuyla tedavisinde kapaklı braketlerin kullanılması ile tedavi verimliliği arttırılarak daha estetik ve stabil sonuçlar sağlanmıştır.

Reduced immune activation or immunosuppression is seen in patients withneurological diseases. Urinary and respiratory infections mainly manifested as septicemia and pneumonia are the most frequent complications following spinal cord injuries and they account for the majority of deaths. The underlying reason of these losses is believed to arise due to impaired immune responses to pathogens. Here, we hypothesized that susceptibility to infections of chronic spinal cord injured (SCI) patients might be due to impairment in recognition of pathogen associated molecular patterns and subsequently declining innate and adaptive immune responses that lead to immune dysfunction. We tested our hypothesis on healthy and chronic SCI patients with a level of injury above T-6. Donor PBMCs were isolated and stimulated with different toll like receptor ligands and T-cell inducers aiming to investigate whether chronic SCI patients display differential immune activation to multiple innate and adaptive immune cell stimulants. We demonstrate that SCI patients' B-cell and plasmacytoid dendritic cells retain their functionality in response to TLR7 and TLR9 ligand stimulation as they secreted similar levels of IL6 and IFNα. The immune dysfunction is not probably due to impaired T-cell function, since neither CD4+ T-cell dependent IFNγ producing cell number nor IL10 producing regulatory T-cells resulted different outcomes in response to PMA-Ionomycin and PHA-LPS stimulation, respectively. We showed that TLR7 dependent IFNγ and IP10 levels and TLR9 mediated APC function reduced substantially in SCI patients compared to healthy subjects. More importantly, IP10 producing monocytes were significantly fewer compared to healthy subjects in response to TLR7 and TLR9 stimulation of SCI PBMCs. When taken together this work implicated that these defects could contribute to persistent complications due to increased susceptibility to infections of chronic SCI patients.

Human intestinal flora comprises thousands of bacterial species. Growth and composition of intestinal microbiota is dependent on various parameters, including immune mechanisms, dietary factors and intestinal motility. Patients with spinal cord injury (SCI) frequently display neurogenic bowel dysfunction due to the absence of central nervous system control over the gastrointestinal system. Considering the bowel dysfunction and altered colonic transit time in patients with SCI, we hypothesized the presence of a significant change in the composition of their gut microbiome. The objective of this study was to characterize the gut microbiota in adult SCI patients with different types of bowel dysfunction. We tested our hypothesis on 30 SCI patients (15 upper motor neuron [UMN] bowel syndrome, 15 lower motor neuron [LMN] bowel syndrome) and 10 healthy controls using the 16S rRNA sequencing. Gut microbial patterns were sampled from feces. Independent of study groups, gut microbiota of the participants were dominated by Blautia, Bifidobacterium, Faecalibacterium and Ruminococcus. When we compared all study groups, Roseburia, Pseudobutyrivibrio, Dialister, Marvinbryantia and Megamonas appeared as the genera that were statistically different between groups. In comparison to the healthy group, total bacterial counts of Pseudobutyrivibrio, Dialister and Megamonas genera were significantly lower in UMN bowel dysfunction group. The total bacterial count of Marvinbryantia genus was significantly lower in UMN bowel dysfunction group when compared to the LMN group. Total bacterial counts of Roseburia, Pseudobutyrivibrio and Megamonas genera were significantly lower in LMN bowel dysfunction group when compared to healthy groups. Our results demonstrate for the first time that butyrate-producing members are specifically reduced in SCI patients when compared to healthy subjects. The results of this study would be of interest since to our knowledge, microbiome-associated studies targeting SCI patients are non-existent and the results might help explain possible implications of gut microbiome in SCI.

Myiasis is an infestation that occurs by flies larvae. Usually it appears in the dead animals residues and garbage but rarely seen at intact skin or necrotic areas. myiasis cases appears uncommon in our country. In this study we aimed to Show patient with myiasis based on squamous cell carcinoma of the auricula who did not considered surgery interference and any therapy.

Garden cress (Lepidium sativum), a member of the Brassicaceae family, is an underutilised crop in Europe and Turkey. The dry matter content, crude protein, ascorbic acid, minerals (N, P, K, Ca, Mg, Na, Fe, B, Cu, Na, Zn, Mn), the total phenolic content and the total antioxidant capacity of two garden cress cultivars, Izmir and Dadas, were studied. The results of mineral element analysis of both cultivars revealed that they had a high P, K, Ca, Mg and Na content. Both cultivars studied appeared to have exceptionally high levels of protein when compared with common vegetables. The mean ascorbic acid content of Dadas and Izmir cultivars were 54 and 74 mg 100 g-1 f.w., respectively. The total phenolic content of the garden cress leaves varied from 0.573 (Dadas) to 0.774 (Izmir) mg GAE · g-1 fw and from 6.332 (Dadas) to 7.401 (Izmir) mg GAE · g-1 dw. Antioxidant activities by 2-diphenyl-1-picryhydrazyl (DPPH) free-radical-scavenging assays for EC50 were determined as 330.99 (Dadas) and 346.65 (Izmir) for fw, and 128.08 and 85.97 (Izmir) for dw, respectively. Based on the results of the experiment reported herein, they may serve as a potential dietary source of some mineral and natural phenolic antioxidants. Our results imply garden cress as potential source for alternative dietary supplements of minerals and natural phenolic antioxidants.

Structurally distinct classes of synthetic CpG oligonucleotides (ODN) differentially activate human immune cells. K-type ODN trigger plasmacytoid dendritic cells (pDCs) to differentiate and produce TNFα. In contrast, D-type ODN stimulate large amounts of IFNα secretion from pDCs. The cell-surface receptor CXCL16 was previously shown to influence the nature and specificity of CpG ODN-induced immune activation. Here, we evaluated the expression and function of CXCL16 on pDC from healthy volunteers. We report that increased CXCL16 expression correlated with enhanced in vitro response exclusively to D-type CpG ODN. Conversely, enzymatic digestion of the receptor resulted in a decrease in IFNα production. Moreover, ox-LDL presence significantly inhibited D-ODN mediated IFNα production by pDCs. Coculture of enriched pDCs with the CXCR6 expressing Jurkat T cells decreased the activation threshold of these cells responding to D-ODN, suggesting that CXCL16/CXCR6 interaction may play an important role in modifying the response of pDCs to environmental danger signals.

İnsanların kendilerini yönetecek olanları belirli bir süre için özgür iradeleriyle kurallara uygun bir şekilde belirlemesine seçim denir. Seçim, çağdaş demokrasilerde yöneticilerin belirlenmesi için vazgeçilmez temel kuralların başında gelir. Siyasal yönetim sistemlerinin gelişimine paralel olarak seçimlerin de geliştiği görülmektedir. 1789 Fransız İhtilali öncesinde yöneticiler seçime başvurmaktan hoşlanmazdı. Antik Yunan ve Roma kentlerinde kenti ilgilendiren bazı konularda sınırlı sayıda halkın oylarına başvurulurken; Ortaçağda ancak kent kilise ve meslek örgütlerinde seçim yapılırdı. Kentlerin büyümesi, burjuva sınıfının güçlenmesi iktisadi yaşamı olduğu kadar siyasal yaşamı da etkiledi. Kent yönetimine katılarak varlıklarını, güçlerini ve yeterliliklerini kanıtlayan burjuvalar devlet yönetimine de katılmak istediler. Geleneksel sistemi kökünden değiştirecek olan bu isteklere yöneticiler pek de sıcak bakmadılar. Kimi ülkelerde yöneticiler halkın devlet yönetimine katılımını reformist uygulamalarla gerçekleştirirken kimi ülke yöneticileri de ülkelerini büyük kanlı devrimlere sürüklediler. Böylece mutlak monarşilerin yerini halkın temsilcilerinden oluşan parlamentolu yeni rejimler almaya başladı. Seçme ve seçilme hakkının varlıklı erkeklere özgü olması tartışmalara yol açtı. Demokrasi halkın egemenliğine dayanan bir rejim olduğuna göre halkın tümünün iradesini yansıtan bir yönetimin getirilmesi zorunlu görüldü. Nitekim büyük bir mücadeleden sonra seçme ve seçilme hakkı zengin-yoksul, erkek-kadın ayrımı yapılmadan tüm halkın temel haklarından biri olduğu kabul edilerek, temsili rejimin vazgeçilmez bir unsuru oldu. Biz, bu makalemizde Türk toplumunun yaşamında önemli bir yer tutan 1912 genel seçimleri sırasında Eskişehir'de meydana gelen olayları inceleyeceğiz. Ancak konunun daha iyi anlaşılabilmesi için seçim olgusunun toplumsal yaşamımızda izlediği gelişme çizgisini de kısaca açıklayacağız.

In this study, the effect of addition of juniper molasses (JM) at a rate of 2, 4, 6 or 8% on fermentation process of milk and some physiochemical and microbiological properties of set type yogurt were investigated. The titratable acidity, pH, viscosity, whey separation, lactic acid bacteria counts (MRS and M17 agar) of experimental yogurt samples were determined during storage at weekly intervals for 28 days. After incubation (3.5 hours), the pH of JM added yogurts were recorded as 4.78-5.02, while the pH of the control was determined to be 4.70. It was also found that the increased JM addition led to an increase in the fermentation time of the milk, to a decrease in the viscosity and serum separation and to an increase in the pH of yogurts compared to the control yogurt samples during storage. In addition, it was determined that lactic acid bacteria counts of experimental yogurts from MRS agar plates decreased rapidly, however, those counts obtained from M17 agar plates decreased slowly after a 7-day storage. It was concluded that, considering the examined parameters addition of 4% JM could be tolerable for the production of fruit yogurt, however, it is suggested that this level should be less than %4 due to intense sour taste of JM. 3. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate early response of retinal sensitivity (RS) and retinal morphology in diabetic macular edema (DME) patients after intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment., Methods: Sixteen eyes of 12 DME patients were included in this study conducted prospectively. All eyes underwent functional and morphologic examination of the macular area using microperimetry and optical coherence tomography (OCT) before and after intravitreal anti-VEGF injection. To determine significant differences between the values, paired t test was used. A correlation between CMT and RS was made using Spearman's test., Results: Patients were evaluated at baseline, one week and one month after injection. The central macular thickness (CMT) decreased significantly from 449.33 ± 100.79 μm to 427.94 ± 85.76 μm to 357.93 ± 75.92 μm. The RS improved significantly from 7.94 ± 6.43 dB to 11.09 ± 7.42 dB at one week and to 14.22 ± 7.66 dB at one month after treatment. The CMT was significant negatively correlated to RS (r=-0.259, p = < 0.001), with decay of 0.025 dB for every 1 μm increase of CMT., Conclusions: Retinal thickening due to DME can be adequately quantified using OCT, while microperimetry can offer information about retinal sensitivity in the exact location. Therefore, microperimetry can be a useful tool in predicting the functional outcome and determining the efficacy of anti-VEGF treatment for DME patients., Competing Interests: Declarations. Ethics approval and consent to participate: No names, personal identification numbers, home addresses, contact information, photographs, or any other data that could be traced back to individual patients were collected. Further, no tissue specimens were analyzed in the project. Ethics approval and consent to participate that this study was approved by “Komite Etik Pusat Mata Nasional Rumah Sakit Cicendo” ethics committee. The requirement for informed consent was waived by “Komite Etik Pusat Mata Nasional Rumah Sakit Mata Cicendo” considering that the study used no sensitive patient information; did not entail any treatment, other interventions, tests, examinations, or interviews; did not affect follow-up; did not expose patients to any risk of physical, psychological or other harm; and used no biological samples. The study adhered to the tenets of the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: Chronic tonsillitis (CT)-adenoid hypertrophy (AH) is the most common cause of obstructive sleep apnea (OSA), which is one of the most common reasons of nocturnal hypoxia in children. However, there is limited information about the relationship between childhood OSA and atherosclerosis or cardiac diseases. In the present study, we evaluated the relationship between mean platelet volume (MPV) and CT-AH which is the most frequent cause leading OSA in children. Methodology : The medical records of 200 children, who underwent adenoidectomy or adenotonsillectomy with a diagnosis of adenoid hypertrophy and/or chronic tonsillitis between October, 2010 and June, 2012, and 240 healthy controls were evaluated. Subjects were classified into 3 groups. Group I consisted of patients who underwent adenoidectomy, whereas Group II consisted of patients who had adenotonsillectomy. Healthy children were employed as control group. White blood cell count (WBC), platelet count (PLT), hemoglobin (Hb) levels and mean platelet volume (MPV) values were recorded individually., Results: MPV values were 6.6±0.8, 6.6±0.7 and 7.3±0.9 in Group I, Group II and control group, respectively. It was found that MPV values in groups I and II were significantly lower than control group. There was no significant difference between group I and II. Conclusion : Obstructive sleep apnea (OSA) caused by CT-AH is associated with low MPV values in childhood.